PHARMACOLOGICALLY ACTIVE COMPOUNDS AND MIXTURES THEREOF, ORGANIC COMPOSITIONS AND METAL SALTS

Abstract: Organic compounds and mixtures thereof and chelates of organic compounds with metal salts which show pharmacological activity in the treatment of cancers and non-malignant tumors, and against bacteria, viruses and fungi. More particularly, mixtures and chelates of metal salts with organic compositions wherein the metal portion is a multivalent metal halide. The compositions of this invention are less toxic than an equivalent amount of at least one separate component thereof. This invention also relates to the use of zinc chloride as a potentiator of organic compounds useful for the treatment of human tumors, and further relates to the use of specific organic compounds for topical treatment of human tumors. Methods of treatment of cancers and non-malignant tumors with the compositions described above are also disclosed, as are methods of treatment of bacterial, viral and fungal infections, and methods of selective debriding and skin ulcers.

Description: PHARMACOLOGICALLY ACTIVE COMPOUNDS AND MIXTURES THEREOF, ORGANIC COMPOSITIONS AND METAL SALTS Field of the Invention This invention relates to pharmacologically active compounds and mixtures thereof and chelates of selected organic compounds as defined herein with and without metal salts. The mixtures and chelates are usef l in the treatment of cancers and non-malignant tumors and as antibacterial, antiviral and antifungal agents. The invention also relates to certain organic lignans and aliphatic acids useful as topical pharmaceuticals against tumors.. Background Art A number of metal salts have been reported to have antitumor activity. The organo-platinum coordination compounds, e.g. cisplatin, are probably the best known. Additionally, colloidal lead phosphate, alkali arsenites, various organo-arsenicals and copper, nickel and cobalt b^tylphthalate complexes have been utilized in the treatment of human cancers. Zinc chloride and other escharotics have been utilized as treatments for human cancers, but, except as used in controlled applications in claemosurgical techniques, such uses generally have not received favorable consideration from the medical profes¬ sion. Zinc chloride, including zinc chloride mixed with a extract from podophyllum, has been used as a fixative in chemosurgical removals of cancerous skin growth with layers of the growths being removed within a short period of time after each application of the fixative. Zinc chloride has also been used in combination with plant materials such as bittersweet root and blood root to cure skin lesions and/or tumors. However, the prior art contains no suggestion that the presence of an organic compound renders a composition containing zinc chloride more effective, more selective, or less toxic in destroy¬ ing diseased or damaged tissue and promoting healing thereafter. A number of articles by Mohs on the treatment of skin cancer (e.g., F. E. Mohs, M.D., and M. F. Guier, PhD., "Pre-Excisional Fixation of Tissues in the Treat¬ ment of Cancer in Rats," Cancer Research, 1:49-51, 1941) disclose the use of a mixture of zinc chloride in an amount of about 40% to 50% by weight of the preparation combined with stibnitε and a plant extract of Sanguinaria canadensis to chemically kill and fix cancerous tissue in situ prior to microscopic excision of the tumor cells. Mohs' article mentions that other plant extracts such as those of Phytolacca decandra, Podophyllum peltatum or Inula helenium may also be used as the agglutinant in his preparation to keep the fixative solution from separating as it stands in the jar. The article does not teach or suggest that the plant extract has activity beyond its stated function to keep the preparation suspended. U.S. 2,344,830, a patent granted to Mohs for the above composition, specifically discloses that his preparation is for conditioning diseased tissue for removal by surgery, and is not used as, nor intended as, a cure for diseased tissue. ϋ.S. 41,315,,.316 to Jonas S. Likens, discloses the use of a compound derived from dried bittersweet root bark (Solanum dolca arum) combined with zinc chloride to form a salve applied topically to remove unwanted skin growths. The bittersweet root extract is identified only by an approximate empirical formula, i ts physico-cfee άcal properties. Booth, et al. , in "Metabolic Effects of Zinc in Intact Cells - Comparative Studies of Zinc Chloride and the Zinc Chelate of Kethoxal bis (thiosemicarbazone) ," 20 Biochem. Pharπt, 3109 (1971), compares the cytotoxic effects on mice bearing transplanted intraperitoneal sarcoma 180 ascites cells of intraperitoneal injections of 20 mg./kg. zinc chloride and 50 mg./kg. of a zinc chelate of Kethoxal bis (thiosemicarbazone) , a known anticancer agent, and found the zinc chelate to be significantly more cytotoxic than zinc chloride alone. The zinc chelate used was not a mixture of the organic with zinc chloride. Ladanyi Patent No.- 4,406,881 discloses the use of a mixture of a mineral acid salt of benzophenanthridine alkaloid and zinc chloride as an antimicrobial agent, and states that, in vivo, a combination of these two ingredi¬ ents was more effective than either ingredient alone against dental plaque-forming microorganisms. Although such escharotics as zinc chloride have long been known to destroy tissue, it has not been known that these escharotics are active in combination with organic compositions as described below to selectively destroy tumor tissue in concentrations lower and less toxic than the threshold concentrations at which such escharotics act alone to destroy tissue. Nordihydroguaiaretic acid (NDGA) has been investi¬ gated for potential antibacterial activity and has been found to possess such activity in vitro. Chaparral tea, which contains NDGA, has also been reported in the last decade to be useful in the treatment of human • cancer ? however, subsequent studies conducted as a result of the alleged anticancer activity have concluded that the tea is not beneficial in the treatment of cancer. Extracts from Larrea have also been utilized in the treatment of Bovine eye cancer. Burk, D., et al., "Hydrogen Peroxide, Catalase Glutathione Peroxidase, Quinones, Nordihydroguaiaretic Acid, and Phosphopyridine Nucleotides in Relation to X-Ray Action on Cancer Cells," Rad. Res. Supp., 3:212-246 (1963) discloses the use of NDGA as a cancer antimetabolic agent in vitro and in vivo, using for the in vivo test an intraperitoneal injection of 400 mg. NDGA (hydroguinone form) per kg, a dosage highly toxic to the host. NDGA was thought to inhibit glycolysis, accounting for its selectivity for tumor cells as opposed to normal cells which do not conduct much glycolysis. Gisvold, et al. , "Lignans from divaricata," J. Pharm Sci., 63:1905-07 (1974) discloses that NDGA in combina¬ tion with ascorbic acid is effective in vivo against Ehrlich ascites tumor in mice, and suggests that similar activity might be shown by dihydroguaiaretic acid, norisoguaiacin, 3'-dimethoxyisoguaiacin, or partially demethylated dihydroguaiaretic acid. Smart, C.R., et al., "Clinical Experience with Nordihydroguaiaretic Acid," Rocky Mountain Med. J. (November, 1970) discloses the successful self-treatment by an 85-year old male of malignant melanoma with two cups per day of chaparrel tea (containing NDGA) for several months. This article also reports negative NDGA screenings by the Cancer Chemotherapy National Service Center for sarcoma 180, mammary adenocarcinoma 755, and leukemia L1210 in mice. Tests of 59 humans with incurable malignancies, using chaparrel tea or pure NDGA at 250 mg. to 3000 mg. per day by mouth, showed 4 significant regressions. A significant number of cases showed tumor stimulation. None of the foregoing articles disclose preparations of NDGA for topical application effective for tumor reduction. Many organic compounds have been found to have anti- tumor effects; however it has not previously been known that zinc and other metal ions are useful as potentiators and enhancers for these compounds in producing antitumor effects. Zinc acetate (1.2%) in combination with erythromycin (4%) has been successful for the topical treatment of acne. See "Topical Erythromycin, Zinc Equal of Oral Tetracycline in Acne," Skin & Allergy News, p. 5, Vol. 14, No, 9, 1983. However, zinc chloride as a potentiator of. organic agents for the treatment of such infections has not previously been known. A. Breathnach, et al., in "Ultrastructural and Biochemical Observations on the Effect of 4-hydroxy- anisole plus Tyrosinase on Normal Human Melanocytes and Kerotocytes in Tissue Culture," Br. J. Cancer, Vol. 47, p. 813-822, 1983, describes the use of 4-hydroxyanisole plus tyrosinase for destruction of melanocytes in vitro. M. Nazzaro-Porro, et al., "Effect of Azelaic Acid on Human Malignant Melanoma," The Lancet, 1109-11 (May 24, 1980), discloses the effectiveness of Cg to C 14 di- carboxylic acids for the topical treatment of cutaneous hyperpigmentary disorders such as chloas a, toxic mela- noderma, lentigo maligna, and malignant melanocyte. Malignant melanomas were treated with a 15% azelaic acid cream twice daily for 16 weeks. Patients were also treated orally. No toxic effects were observed, and tumor reduction occurred in all cases. The article disclosed that azelaic acid is a tyrosinase inhibitor. M. Nazzaro-Porro, et al., "Effect of Dicarboxylic Acids on Lentigo Maligna," J_ j _ Invest. Dermatol., 1979, 72/6 (296-305) discloses the use of a 15% azelaic acid ointment to successfully affect abnormally active or structurally disordered melanocytes in lentigo maligna. M. Nazzaro-Porro, et al., "Local Treatment of Lentigo Maligna with Azelaic Acid,* Arch. Dermatol. Res. (Germany, West), 1981, 271/2 (197-203) describes the use of azelaic acid in an ointment to treat lentigo maligna. Results were not convincing in clinical aspects. M. Nazzaro-Porro, et al., in "Beneficial Effect of 15% azelaic acid cream on acne vulgaris," Br. J. Dermatol. , Vol. 109, pp. 45-48, 1983 describes the suc¬ cessful use of azelaic acid cream to treat acne. H.E. Willshaw, et al., "Azelaic Acid in the Treatment of Ocular and Adnexal Malignant Melanoma," Br. J..Opthalmol. , 1983, 67/1 (54-57) describes the unsuc¬ cessful use of azelaic acid both locally and systemically in treating malignant melanoma lesions of the eye and its adnexa. A.S. Breathnach, et al., "Effect of Dicarboxylic Acids on Normal Human Melanocytes in Culture," Br. J. Dermatol, Vol. 99/Suppl. 16 pp. 19-20, 1978 reports that dicarboxylic acids have a stimulatory effect on melano¬ cytes of an original culture generation which may result in destruction of melanosomes, but do not prevent growth of, or cause damage to second generation. German Patent DE 2817133 dated November 2, 1978, to M. Nazzaro-Porro, (corresponding to Canadian Patent No. 1,137,873 submitted herewith) discloses the use of azelaic acid and other dicarboxylic acids having 7 to 13 carbon atoms for the treatment of hyperpigmental derma- toses. None of the foregoing art suggests or discloses that dicarboxylic acids may be potentiated or enhanced in their antitumor activity by multivalent metal salts, that smoasocarboxylic acids might be effective, or that the organic acids might be effective against non-hyperpigmen- tary disorders such as human breast tumors. Taken as a whole, the cited art teaches away from, as much as suggests, the use of dicarboxylic acids even for the treatment of hyperpigmentary skin disorders. Additionally, many organic compositions have been investigated for their potential biological and pharma¬ cological activities. A variety of activities have been reported including antiviral activities for some flavo- noids, antimicrobial activities for some phenols and antitu or activities for some lignans and some phenols. However, much of this work has been conducted jLn vitro at a cellular level with different conclusions being drawn by different investigators. In fact, a recent article in J. Nat. Prod., 42:85-91 (1975), which collated the results of 217 flavonoids tested in the screening program of the National Cancer Institute, concluded not only that no correlation can be drawn between KB cytotoxicity screens and animal screens for antitumor activity of flavonoids, but also that flavonoids do not warrant further investigation as antitumor agents. Finally, both metal compounds and many organic compositions, including phenolic compositions, have been tested for various antimicrobial activities. Many of these compounds do exert such activity. Some of the compounds and compositions of this invention are discussed in co-pending applications Serial Nos. 365,784, 436,444 and 436,425, all commonly assigned to the assignee hereof. The contents of said applica¬ tions are fully incoporated herein by reference. Summary of the Invention This invention relates to organic compounds and mixture thereof, with and without metal salts, and to organo-metalli chelates, which show pharmacological activity in the treatmenfc f cancers and non-malignant tumors. Prefer¬ ably, the metal salts are zinc salts, and preferably the chelates are zinc chelates. The mixtures and chelates of - this invention are generally more effective and less toxic than effective doses of the separate components thereof. The compositions of this invention are useful in the treatment of bacterial, viral and fungal infections, and for the selective debriding of skin ulcers. In addition, they ar useful far the healing of lesions, acne, warts and inflammato disorders. This invention also relates to the use of metal ions r e.g. zinc, as enhancers and potentiators of organic compositions useful for treating tumors. This invention further relates to methods of treat¬ ment of cancers and non-malignant tumors, to methods of treatment of bacterial, viral and fungal infections, and to selective debriding of skin ulcers with the composi¬ tions described above. Detailed Description of the Preferred Embodiments I. Organic Compounds and Escharotics. Escharotics such as zinc chloride and other metal halides owe their activity to their ability in sufficient concentrations to indiscriminantly destroy living tissue with which they are placed in contact. These escharotics do not selectively destroy diseased tissue, such as tumor tissue, to the exclusion of healthy tissue. When suffi¬ cient concentration of the escharotic to be effective in eradicating a tumor is placed in contact with the tumor, it will also destroy any healthy tissue with which it comes in contact. It has now been discovered that when such escharotics are combined with the organic composi¬ tions described herein, the combinations are effective for the eradication of tumors even though the concentra¬ tion of the escharotic is less than that which would be effective by itself. Also, it has been found that when tumor sizes are used, less of the organic compositions are needed for activity when used in combination with subactive concentrations of escharotic. The fact that the organic compositions and the escharotics enhance or extend the activity of each other means that lesser concentrations of toxic escharotics and organic compositions nee be used to obtain pharmacologi¬ cal activity. Furthermore, with proper selection of the organic components, greater selectivity for tumor tissue may be achieved than with escharotic alone. The multivalent metal salts of this embodiment are zinc, trivalent chromium, yttrium, divalent cobalt, platinu trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals. Generally, the highest oxidation state of a metal is preferred over lower oxidation states thereof. The most preferred metal salts are zinc salts, more preferably halides, with zinc chloride being the most preferred zinc halidei Escharotic metal salts including zinc chloride comprise the most highly preferred class of metal salts. A broader preferred class of metal salts comprises zinc, mono- and divalent copper, divalent cobalt, trivalent iron, antimony, cadmium and vanadium salts. Within this class, the halides are preferred, and the chlorides most preferred. Zinc salts including nitrates, sulfates, acetates and halides also comprise a preferred class. Another, broader contemplated class comprises salts of all the metals above listed except the rare earth metals, preferably the halides thereof, and more preferably the chlorides thereof. A wide range of organic compounds are useful for the reduction of tumors in combination with metal salts as defined herein. A mixture is provided comprising one or more of the above-described escharotics and one or more organic compounds as defined herein. A most preferred embodiment of this invention utilizes meso-nordihydroguaiaretic acid (NDGA) as the organic component of the mixture and zinc chloride as the metal salt, the milxture being contained in a suitable pharmaceutical carrier. For ^ topical use, carriers such as creams, ointments and solutions are provided. Poly¬ ethylene glycols of varying molecular weights are examples of suitable carriers. A preservative such as butylated hydroxytoluene (BHT) may be added as well as chelating agents such as ethylenediaminetetraacetic acid (EDTA) . For topical application the mixture may comprise about 1-30 weight percent zinc chloride, and about 1-18 weight percent nordihydroguaiaretic acid, with optional minor portions of ethylenediaminetetraacetic acid, and butylated hydroxytoluene, in a suitable carrier such as a mixture of stearyl alcohol, and polyethylene glycol, with major portions of said polyethylene glycol having a molecular weight of around 400, and minor portions thereof having a molecular weight of about 3000 to 4000, said polyethylene glycols being present in proportions such that they provide a consistency suitable for topical application. A typical mixture comprises about 4.60% NDGA, about 29.8% zinc chloride, about 14.7% ethylenediamine¬ tetraacetic acid, about 1.1% BHT, about 0.50% stearyl alcohol, about 18.3% purified water, about 26,4% poly¬ ethylene glycol having an average molecular weight of about 400 and about 4.5% polyethylene glycol having an average molecular weight of about 3350. A further preferred mixture contains NDGA and zinc chloride in the proportions defined above, but does not contain edetiσ acid or BHT. These compositions may be prepared by any means known to the art to obtain uniform and stable mixtures. Other typical compositions comprise: (1) about 4.6% NDGA, about 1.1% BHT, about 0.49% ethylenediamine¬ tetraacetic acid and about 1.0% zinc chloride, with the balance comprised of water and polyethylene glycols; (2) about 4.6% NDGA, about 1.1% BHT, about 2.47% ethylene¬ diaminetetraacetic acid and about 5.0% zinc chloride, with water and polyethylene glycols; and (3) about 4.6% NDGA, about 1.1% BHT, about 4.93% ethylenediaminetetra¬ acetic acid and about 10.0% zinc chloride with water and polyethylene glycols. Compositions (1) , (2) , and (3) without ethylenediaminetetraacetic acid or BHT are also preferred mixtures. The foregoing compositions may be made up with differing viscosities, depending on whether they are intended for topical use, injection, or other means of administration, by adjusting the relative amounts of polyethylene glycol 400 and polyethylene glycol 3350. Another typical composition comprises the above proportions of NDGA, ZnCl 2 , BHT and ethylenediaminetetra¬ acetic acid in a slow-release ointment formula which releases zinc chloride- at a slower rate than NDGA. A preferred preparation for sustained-release topical use contains NDGA at a concentration of between about 5 and about 15% and zinc chloride at a concentration of between about 5 and about 30%, and releases zinc ions at an average rate of between about 0.5 and 1 weight percent per hour, while releasing NDGA at a rate propor¬ tional to its concentration. In general, many of the compositions according to the invention are of the general formula: wherein, D,E,F,X,Y,Z, may be H?0H; O-Alkyl or O-Acyl optionally substituted with hydroxy, alkoxy, substituted amino, carbalkoxy, or carboxy? R.-R, may be H? lower alkyl or lower alkoxyl optionally substituted with hydroxy, alkoxy, substituted amino, carboxyl, or carbalkoxyl; hydroxy? carbonyl; alkoxy? atyl? atalkyl; n may be 0 to 5; any of the aromatic rings in the molecule may contain up to 3 substituents from the following lists hydroxy; alkenoxy; alkyl, alkoxy or alkanoyl optionally substituted by hydroxy, alkoxy, substituted amino, carboxy, or carbalkoxy; CF^ halo; carboxy; carbalkoxy; cyano? hydroxymethyl; sulfonic acid; sulfonamido; aminosulfonyl ti.e. - NHSO^R)? nitro; alkoxycarbonyloxy? aminocarbonyloxy ? aroyloxy; aralkanoyloxy; heteroaroyloxy; glycosidyloxy; and any two phenolic groups may be joined together by either of the rings A or B may be replaced by- cyclohexyl, napthyl, tetrahydronapthyl, pyridyl, piperidinyl, quinolinyl, indanyl, indenyl ? any of the groups R, to R β may be joined together to form together with the other carbons to which they are attached, a 5, 6, or 7 membered ring optionally in - terrupted by an oxygen atom, or containing an oxygen atom and a carbonyl substituent,or containing a carbonyl substituent? any of the groups 3 to R, may be joined to ring A to form with it a 5, 6, or 7 membered ring? any of the carbons in the chain between rings A and B, may be attached by a bond to the © position on ring A to form a 5, 6, or 7 membered ring. More specifically, organic compounds useful in embodiments of the invention comprise: A-; Bridged Phenolic Compounds. 1. Catecholiσ butanes of the formula: where R. and R 2 are independently H; 1-12 alkyl? 1-12 alkenyl; 1-12 alkoxy; 1-12 alkenoxy; (C0) n (CH 2 m C0 2 ) Ra. where n=0-l, m=l-4, p=0-l, and Ra a is independently H, 1-12 alkyl, and 1-12 alkenyl; and glycoside moieties and R-substituted glycoside moieties wherein any of the hydroxy1 hydrogens thereof may be replaced by R, with R being independently 1-2 alkyl, and 1-2 alkoxy; and taken together are methylene; R_, R„ and R g may be attached to any separate location C,-C 8 of their benzene ring, and are indepen¬ dently H; O; OR, (with R. defined as above) ; and when R_ and R g or R„ and R g are adjacent, taken together they may be methylene? - and R. are independently H, CH,, C,H-, CHO and COOH; and 5 and R g are independently H, OH, 0CH 3 and O. A class of useful compounds of this invention corresponding to Formula I comprises those listed below exemplifying Formula II as well as the following: 3, " 4,2* ,5'-quatrahydroxy-l,4-diphenylbutane; 2',3', ',3,4- pentahydroxy, 1,4-diphenylbutane; 3',4' ,5* , 3,4-penta- hydroxy, 1,4-diphenylbutane; and l-(3,4-dihydroxyphenyl) , 4-phenylbutane. Also included within the scope of this invention are those having trifluoromethyl substituents in place of methyl substituents, e.g. l-(3,4-dihydroxyphenyl)-4-(3,5- ditrifluoromethylphenyl) butane. 2. Preferred compounds of Formula I correspond to the formula: where Ri-Rg are as defined in Formula I, and OR 1 ' and OR 2 ' are defined as R j and 2 , but may vary independently of R, and 2 . A preferred class of useful compounds of this invention are nordihydroguaiaretic acid and its analogs of Formula II comprising: nordihydroguaiaretic acid (1,4-bis-(3,4-dihydroχyphenyl) butane); dihydroguaiaretic acid (l,4-bis-(3-methoxy,4-hydroxyphenyl) , 2,3-dimethyl- butane) ; nordihydroguaiaretic acid tetraacetate (1,4- bis(3,4-diacetoxyphenyl) ,2,3-dimethylbutane) ; nordihydro¬ guaiaretic acid propionate (1,4-bis-(3,4-dipropyloxy- phenyl) , 2,3-dimethylbutane) ; nordihydroguaiaretic acid, glycoside (1-(3-hydroxy, 4-glucaryl-O-phenyl) , 4-di- hydroxyphenyl, 2,3-dimethyl-butane or 1-(4-hydroxy, 3-glucaryl-O-phenyl) , 4-dihydroxyphenyl, 2,3-dimethyl- butane) ; nordihydroguaiaretic acid glycoside tetraacetate (l-(3-hydroxy, 4-tetraacetoxyglucaryl-O-phenyl) , 4-di- hydroxyphenyl, 2,3- imethylbutane or l-(4-hydroxy, 3-tetraacetoxyglucaryl-0-phenyl) , 4-dihydroxyphenyl, 2,3-dimethylphenylbutane) ; nordihydroguaiaretic acid diphenoxyacetic acid diethyl ether (1,4-bis (3-dihydroxy) 4-diethylcarbonylmethoxyρhenyl) , 2,3-dimethylbutane or 1,4-bis (4-dihydroxy, 3-diethylcarbonylmethoxyphenyl) , 2,3-dimethylbutane) ; nordihydroguairetic acid triphenoxy- acetic acid diethylether (l-(3-hydroxy, 4-ethylcarbonyl- methoxyphenyl) , 4-(diethylcarbonylmethoxyphenyl) , 2,3-di- methylbutane or l-(4-hydroxy, 3-ethylcarbonylmethoxy- phenyl) , 4-(diethylcarbonylmethoxyphenyl) , 2,3-dimethyl- butane) ? nordihydroguaiaretic acid tetraethylhemisuccinate (1,4-bis(tetraethylhemisuccinylphenyl) , 2,3-dimethylbutane? nordihydroguaiaretic acid tetramethylether diol (1,4-bis (3,4-dimethoxyphenyl) 2,3-dimethyl, 1,4-dihydroxybutane) ? nordihydroguaiaretic acid dimethylene ether dione (1,4-bis (3,4-dimethylenedioxyphenyl) 2,3-dimethyl, 1,4-dioxo- butane) ? nordihydroguaiaretic acid tetramethylether dione (1,4-bis (3,4-dimethoxyphenyl) , 2,3-dimethyl, 1,4-oxo- butane) . A broader preferred class includes desmethyl nordi¬ hydroguaiaretic acid (1,4-bis (3,4-dihydroxyphenyl) butane) ? desmethyl nordihydroguaiaretic acid tetramethyl¬ ether (1,4-bis (3,4-dimethoxyρhenyl) butane, and other desmethyl analogs of the compounds of the preferred class listed above. Also included within the scope of this invention are compounds corresponding to Formula II terminating in one or more nitro groups, e.g. nordihydroguaiaretic acid tetramethyl carbamate. 3. Included within the scope of this invention are stereoisomers of the above compounds in which R 3 and j are not H, and are in d,l-conformation, it being under¬ stood that Formula I includes such compounds as well as those having a meso conformation. Specifically, such steroisomerism occurs at positions 2 and 3 of the butane chain: ( - j -Rg are as defined in Formula I above except that R 3 and R. are not H )).. A preferred, class of such compounds comprises d,l~forms of the compounds of Formula II exemplified by ,1-nordihydroguaiaretic acid and the d,l-isomers of the nordihydroguaiaretic acid analogs listed above as a preferred class. A broader class of such compounds comprises the d # l-isomers of the compounds listed above as exemplifying Formula I. 4. Also included within the scope of this invention are tetralins analogous to the compounds of Formula I wherein the phenyl group attached to C. of the butane chain is also attached (by C g thereof) to C. of the butane chain: where and R-.-R g are as defined in Formula I above. A preferred class of such compounds comprises tetralin analogs of the compounds of Formula II, exempli¬ fied by norisoguaiacin and tetralin analogs of nordihydro¬ guaiaretic acid and the analogs thereof listed above as preferred classes. A broader class of such compounds comprises tetralin analogs of the compounds of the broader classes listed above. 5. Also included within the scope of this invention are catecholic butenes analogous to the compounds of Formula I wherein double bonds may occur at C.-C 2 , C 2 -C 3 , C 3 ~C 4 , or at both C.-C 2 and C 3 -C.: where R I ~ R Q are as defined in Formula I above. A preferred class of such " compounds comprises butene analogs of the compounds of Formula II exemplified by I,4-bis-(3,4-dimethylenedioxyphenyl) 1,3-butene and 2,3-bis (3,4-dimethoxybenzyIidene) succinic acid, and butene analogs of the compounds listed above as preferred classes of Formula II. A broader class of such compounds comprises 1-(3,4-diacetoxyphenyl)-4-phenyl-buta-l,3-diene? and l-(3,4-dihydroxyphenyl)-4-phenylbutadiene and analogs thereof in which the substituents at the 3 and 4 position of the phenyl may be, independently, OH, and OR wherein R is C.-C. alkyl and/or alkoxy, or taken together, the substituents are methylenedioxy. A broader preferred class comprises the foregoing together with other butene analogs of the compounds listed above as broad classes of Formula I. Also included within the scope of this invention are compounds having trifluoromethyl substituents rather than methyl substituents, e.g. l-(3,5-ditrifluoromethylphenyl)- 4-(3,4-dimethoxyphenyl)-l-butene? and compounds having nitro substituents, e.g. l-(3,5-dinitrophenyl)-4-(3,4-di- methoxyphenyl)-1-butene. 6. Also included within the scope of this invention are 1,3-butene analogs of the compounds of Formula V in which C- and C 3 of the butane chain are replaced by N: wherein R., 2 , R, ' and R 2 * are defined as in Formula II above, and R and R ' are defined as R. and R. 1 respec¬ tively, and when R *0 and R,'O are adjacent they may be, taken together, methylene. A preferred class of such compounds includes vanillin azine and syringaldezine, and catecholic analogs thereof wherein all but the 3' and 4* hydroxy substituents of one phenyl group may be replaced, independently with R, wherein R is H, 1,4 alkyl, or 1-4 alkoxy, and two adjacent such substituents taken together may be ethylenedioxy. 7. Also included within the scope of this invention are 1,4-bis phenethylbenzenes and 1,4-bis styrylbenzenes of the formula: wherein R«, R 2 , R.* and R 2 ' are as defined in Formula II above, and there may be double bonds independently at 1-2. and l'-2' of the chains. A preferred class of such compounds comprises 1,4-bis-(3,4-dihydroxyphenethyl) benzene; 1,4-bis-(3,4-di- methoxyphenethyl) benzene; 1,4-bis-(3,4-dihydroxystyryl) benzene; and 1,4-bis-(3,4-dimethoxystyryl) benzene. 8. Also included within the scope of this invention are catecholic propanes, pentanes, pentenes, hexanes and hexenes analogous to the compounds of Formula I, but having 3, 5- or 6-member carbon bridges between the phenyl groups rather than 4-member chains. A preferred class of such compounds comprises 1,6-bis-(3,4-dihydroxyphenyl) hexane and other hexane analogs of the compounds listed above as preferred classes of Formula II. A more preferred class of such compounds comprises those having no substituents on the hexane bridge other than the two phenyl groups at posi¬ tions 1 and 6. B. Monophenolic Compounds. 1. Phenolic acids and acidic anhydrides selected from the group consisting of compounds of the formula: wherein ^-^ are inde P en<3enti Y H » 0H » 1-12 alkyl, 1-12 alkenyl, 1-12 alkoxy, 1-12 alkenyoxy, 1-12 alkylcarboxy, 1-12 alkenylcarboxy, or, taken together, are methylene dioxy? n = 0-1 3 - 1-12 alkyl, 1-12 alkenyl, hydroxy-l-5-alkyl, hydroxy-l-5-alkenyl; oxy-1-5-alkyl; oxy-1-5 alkenyl, or oxo-l-5-alkyl, oxo-1-5 alkenyl; and , is an acid moiety, a 1-5 alkyl ester moiety, a 3-6 carbon dicarboxylic acid moiety, or a 3-6 carbon dicarboxylic acid anhydride moiety. A preferred class of such compounds comprises 3,4-dihydroxybenzoic acid; ethyl 3,4-dihydroxybenzoate; cinnamic acid; mandelic acid; p-hydroxycinnamic acid; 3,4-dihydroxycinnamic acid; 3,4-dihydroxyphenylacetic acid; 4-hydroxy, 3-methoxycinnamic acid; 2-(3,4-dimethoxy- benzylidene) succinic acid; and 2-(3,4-dimethoxybenzyli- dene) succinic anhydride. Also included within the scope of this invention are compounds in which » is an amine acid moiety. A pre¬ ferred compound of this type is 3-(3,4-dimethoxyphenyl) propylamine, N-formic acid, N-acetic acid and its hydro- chlorides and hydrobromides. Also included within the scope of this invention are compounds wherein R. and R-» rather than being in the 3 and 4 positions, as shown in Formula VIII, are rotated to other adjacent positions. A preferred compound of this type is 2,3-dihydroxybenzoic acid. 2. Substituted catecholic compounds of the formula: wherein R. and R 2 are independently, 1-12 alkyl, 1-12 alkenyl, or taken together are methylene; and 3 is 1-12 alkyl, 1-12 alkenyl, formyl, hydroxy-1- 12-alkyl, hydroxy-1-12-alkenyl, oxo-l-12-alkyl, or oxo-l-12-alkenyl. A preferred class of such compounds comprises 4-methyl catechol; 4-tertbutyl catechol; 3,4-dimethoxy- phenyl ethanol? 3,4-dihydroxybenzaldehyde; vanillin; 3,4-dimethoxyacetophenone; and 3,4-methylenedioxypropio- phenone. Also included within the scope of this invention are compounds in which R 3 is an amine moiety. Preferred compounds of this type are 3,4-dihydroxybenzylamine and 3-(3,4-dimethoxyphenyl) propylamine, their hydrochlorides and hydrobromides. Also included within the scope of this invention are compounds in which the phenyl group or substituents bear one, two or more simple substituents, including halo, nitro, sulfato amino, and the like. A preferred compound of this type is 5-nitrovanillin. Also included within the scope of this invention are compounds wherein R,0 and R,0, rather than being in the 3 and 4 positions, as shown in Formula IX, are rotated to other adjacent positions, and alkyl portions of R 3 are unbranched. Preferred compounds of this type are 2,3-di- hydroxybenzaldehyde and 3-propyl catechol. 3. Phenolic compounds of the formula: wherein R. is H or CH 3 ; R 2 and R 3 are independently H and 1-12 alkyl, A preferred class of such compounds comprises phenol ? 2-tertbutylphenol? 3-tertbutylphenol? 4-tertbutyl- phenol ? thymol ? and 2,3-dimethylphenol. ** Also included within the scope of this invention are compounds in which the phenyl group or alkyl substituents bear one, two or more simple substituents including halo, nitro, amino sεclfato, and the like. A preferred class of compounds of this type comprises picric acid? o-anisidine; 2-aminoρheπol? and pentafluorophenol. 4. Substituted resorcinols of the formula: wherein R. and 2 are independently H or CH 3 ; and R 3 is 1-12 alkyl. A preferred class of compounds of this type comprises orcinol; 4-ethyl resorcinol; and olivetol. 5. Quinones and hydroquinones of the formula: wherein R. and R 2 are independently H and CH 3 ; and wherein 3 and R. are independently H and OH. A preferred compound of this type is hydroquinone. Another preferred class includes both hydroquinone and 2,5-dih roxy-p-benzoquinone. Also included within the scope of this invention are compounds wherein the phenyl group and/or alkyl substitu¬ ents bear one, two or more simple substituents including halo, nitro, amino, sulfato and the like. A preferred compound of this type is chloranil. C. Multinuclear Ring Compounds, 1. Naphthalenic compounds bearing oxygen-containi substituents of the formula: wherein n is 0-1; R. and R 2 are independently OH, CHO, and COOH * A preferred class of such compounds includes 2,3- dihydroxynaphthalene; 1-naphthaldehyde; and 2-naphthalde- hyde. 2. Flavones, flavanones, cou arins, quinizarins, ellegic acids, and purpurogallins, bearing 0-2 substitu¬ ents per ring, said substituents being independently 1-12 alkyl, hydroxyl, 1-12 alkoxy, formyl, carboxyl and Flavanone A preferred class of such compounds comprises flavone; flavanone? quercetin; 4-methyl esculetin; quinizarin; ellegic acid and purpurogallin trimethyl ether. Also included within the scope of this invention are compounds wherein the rings or alkyl substituents bear one, two or more simple substituents including halo, nitro, amino, sulfato, and the like. A preferred com¬ pound of this type is calcein blue. A further contemplated class of compounds represented by the above formulae comprises flavonoid compounds, both agylcones and glycosides, such as flavones, isoflavones, anthocyanins and flavans, and pharmaceutically acceptable salts thereof, with cations as defined above. Examples of flavones are: flavanol (3-hydroxyflavone) ; (3,5,7-trihydroxyflavone)? (3,3*4'-trihydroxyflavone) ; (3,4* ,5-trihydroxyflavone) ; datiscetin (2' ,3,5,7-tetrahydroxyflavone) ? fisetin (3,3' ,4* ,7 tetrahydroxyflavone) ? (3,3' ,4*-trimethoxy- 7-hydroxyflavone) ? (3,3*,4' ,7-tetramethoxyflavone) ? morin 2*,3,4' ,5,7-pentahydroxyflavone) ? (8-hydroxykaempferol) kaempferol (3,4' ,5,7-tetrahydroxyflavone) ? quercetin (3,3 f ,4*,5,7-pentahydroxy-flavone) ? quercetagetin (3,3' ,- 4 r ,5,6,7-hexahydroxyflavone) ? quercetin 3,3'-dimethyl- ether? quercetin-7,3'-dimethylether; quercetin 3'-methyl- ether? kaempferol .(3,4* ,5,7-tetrahydroxyflavone) ; kaerop- ferol-3,7-dimethylether; kaempferol 3-methylether; kaempferol 7-methylether; kaempferol 3,4'-dimethylether; quercetin 3,7,3* ,4'-tetramethylether; quercetin 3,7,3'τ trimethylether; quercetin 7,3' ,4'-trimethylether; quer¬ cetin 3,7-dimethylether? lutεolin 7,3'-dimethylether (3' ,4 r ,5,7-tetrahydroxyflavone) ? luteolin 3'-methylether? apigenin 7-methylether (4' ,5,7-trihydroxyflavone) ? rutin • (quercetin-3 rutinoside) 3,3' * ,5,7-pentahydroxyflavone- 3-rutinoside; chrysin (chrysoeriol 6,8-9-C-glucoside) 5,7-dihydroxyflavone; isoquercetin 3,3' ,4' ,5,7-penta- hydroxyflavone-3-glucoside; kaempferol 3-O-rhamnosylgluco- side (3,4' ,5,7-tetrahydroxyflavone) ? rhamnetin-3-o-rhamno- sylglucoside (3,3' ,4' ,5-tetrahydroxy-7-methoxyflavone) ; myricetin (3,3' ,4',5,5'7-hexahydroxyflavone) (dihydro- myricetin 3' ,5-dimethylether) ; hesperetin (herbacetin) 3,7-dimethylether; (3' ,5,7-trihydroxy-4'-methoxyflavanone)? quercimeritrin C 2i H 20°12 ? 3 ' 3 ' ,4 ' ,5,7-pentahydroxy- flavone-7-D-glucoside [gossypitrin C 21 H 20°13^ 3,7,3'- trimethylether. Examples of flavans include catechin (3 ,3 * , 4 * ,5 ,7- flavanpentol) ; gallocatechin? polydine? adzelechin, eupatilin and 4 ' -demethyl-eupatilin. Examples of anthocyanins include delphinidin (3 ,3 * ,- 4 * ,5 ,5 * , 7-hexahydroxyflavilium) ? leuteoliniden? cyaniden (3 ,3 * , 4 ,5 , 7 -pentahydroxy f lavylium) ? peonidu (3 ,4 * ,5 ,7- tetrahydroxy-3 ' -methoxyf lavylium) ? yrillidin? and enidin. D * Aliphatic Acids, Aldehydes and Alcohols. Active aliphatic compounds of this invention are preferably unbranched chains containing oxygen and having four to twelve carbon atoms. A preferred class of aliphatic acids of this inven¬ tion includes dicarboxylic acids having four to twelve . carbons. Most preferred is the class comprising adipic acid, azelaic acid, lauric acid, and oxydiacetic acid. A preferred aliphatic alcohol of this invention is lauryl alcohol. A preferred aliphatic aldehyde of this invention is octyl aldehyde. Also included within the scope of this invention are aliphatic cyanides having four to twelve carbon atoms. A preferred compound of this type is n-octyl cyanide. E. Other Compounds Other useful compounds in accordance with the invention include compounds of the formula: . • • where Rl and R2 are, independently, H and CH 3 , or taken together, are CH 2 ; where .R3 is a dienoic 4-12 fatty acid moiety; and where R4 is a dienoic 4-12 fatty acid moiety or a ' 4-12 " mono or dialkene moiety. Preferably Rl and R2 are H; and R3 is deca-l(E) ,4(E)' fiaasnyl " or octa-2(Z)-enyl; and R4 is nona-9-carboxy,l(E)- - Ej-dienyl or deca-10-carboxy,2(Z) ,5(Z)dienyl? ■ where Rl is CH 2 , 0, NH, CF 2 or CHF; and where R2, R3, R4 and R5 are, independently, F and H. i Preferably Rl is CH, and R2 and R3 are F and R4 and R5 are .H; or Rl is CH, and R2 and R3 are H and R4 and R5 are F? or Rl is CF 2 and R2, R3, R4 and R5 are H; or Rl is O and R2, R3, R4 and R5 are H; or Rl is NH and R2, R3, R4 and R5 are H. Where only one fluorine is present, it is preferred that this fluorine be such as to form an L-- fluoro-compound; XXIII. Where R is C00H, CH 3 , or CHO. Where R is COOH, CH 3 or CHO ; Where R is COOH, CH 3 or CHO ; Where R is COOH, CH 3 or CHO Compounds illustrative of Formula XXI are: .4-(deca-l (E) ,4 (E)-dienyl-5-(nona-9-carboxy-l(E) ,4(E)dien- yl)catechol? and 4-(octa-2(Z)-enyl)-5-(deca-10-carboxy- .2(Z) ,5 (Z)-dienyl)catechol. Compounds illustrativeofFormulaXXII are 7,7-difluoro- ,5 (E) ,8 (E) ,11 (E) ,14 (E)eicosatetraenoic acid; 7(L)-fluoro- 5,(E) ,8 (E) ,11 (E) ,14 (E)eicosatetraenoic acid; 10,10-di- fluoro-5 (E) ,8 (E) ,11 (E) ,14 (E)eicosatetraenoic acid; 10 (L)-fluoro-5 (E) ,8 (E) ,11 (E) ,14 (E)eicosatetraenoic acid; 13,13-difluoro-5 (E) ,8 (E) ,11 (E) ,14 (E)eicosatetraenoic acid; 13 (L)-fluoro-5(E) ,8 (E) ,11 (E) ,14 (E)eicosatetraenoic acid; 10-oxanorarachidonic acid; 10-azanorarachidonic acid. i A compound'illustrative of Formula XIIIis 5-hydroxy- borono-,6(Z) ,8(E) ,11(E) ,14 (E)-eicosatetraenoic acid. A compound illustrative of Formula XXIV is 12-hydroxy- bprono-5(E) ,8(E) ,10(Z)14 (E)eicosatetraenoic acid. A compound illustrative of FormulaXXV is 11-hydroxy- "borono-5 (E) ,8 (E) ,12(Z) ,14(E)-eicosatetraenoic acid. - : ' A compound illustrative of Formula XXVI is 15-hydroxy-- borono-5.(E) ,8 (E) ,11(E) ,13 (Z)-eicosatetraenoic acid... , General Considerations relating to the Organic Compounds of this Invention. Compounds possessing substantially the same proper¬ ties as those defined above, which are commercially available or can be prepared by means known to the art and are equivalents thereof, are those bearing one, two or more additional simple substituents, including but not limited to, halo, e.g., chloro; bro o; trifluoromethyl; nitro? sulfato? sulfonyloxy; carbo-lower-alkoxy, e.g., carbomethoxy; carbethoxy; amino; mono- and di-lower-alky1- amino, e.g., methylamino; ethylamino; dimethylamino; ethylethylamino? amido; cyano; etc. Also included within the scope of this invention are pharmaceutically acceptable salts of the foregoing organic compounds, including those having alkali, prefer¬ ably sodium and other alkali metal cations, alkaline earth metal cations, and other metal cations including zinc, aluminum, and cationic forms of the other metals listed above as cations of the multivalent metal salts with which the organic compounds of this invention are mixed. Preferred salts of the organic compounds are sodium and zinc salts. A "contemplated class" of compounds for purposes of claims drawn to such class, may be a class consisting of any single compound embraced by the generic and subgeneric formulae herein, and/or named herein, a class consisting of a homologous series containing any such single com¬ pound, a class -consisting of any such single compound and isomers thereof, a class consisting of any such single compound and analogs thereto, a class consisting of any combination of such single compounds, including structur¬ ally related compounds, and compounds having similar degrees of tested effectiveness. G. Metal Salts. The metal salts utilized in the mixtures of the present invention have as the metal component a multi¬ valent metal. Examples of the metal portion of the salt include one or more of the metals, zinc, trivalent chromium, yttrium, divalent cobalt, nickel, magnesium,platinum aluminum, onovalent copper, divalent copper, trivalent iron, trivalent cobalt, cadmium, antimony, mercury, rubidium, vanadium, and other rare earth metals. The salt is preferably a halide and the more preferred salt is a chloride. Zinc salts, including halides, acetates, nitrates and sulfates, preferably halides, and more preferably chlorides, comprise highly preferred classes of metal εalts. The foregoing highly preferred salts, plus mono- and divalent copper, divalent cobalt, cadmium, antimony, trivalent iron and vanadium salts, preferably halides, and more preferably chlorides, comprise further preferred classes of metal salts. The most preferred metal salt is zinc chloride. H. Methods of Preparation When the mixture is to be applied topically as, for example, in the treatment of a tumor, wart or microbial affliction of the integument, it is preferred that the metal salt have the ability, though possibly only in higher concentrations than used in the mixtures of this invention, to exert an escharotic or keratolytic action. In addition to the organic composition and the metal salt, the mixture can contain pharmaceutically acceptable chelators and/or antioxidants. Examples of chelators include urea, EDTA and its salts, diethylenetriamine tetraacetic acid (DTPA) and its salts, ethylenediamine- diacetic acid (EDDA) and its salts, nitrilotriacetic acid (NTA) , ethylenediamine, salicylic acid, citric acid, - gluconic acid, nucleic acid, oxalic acid, phosphates, sulfates, phospholipids, and amino acids. Examples of antioxidants include BHT (butylated hydroxytoluene) , BHA (butylated hydroxyanisole) , ascorbate, citric acid, ethoxyguin, and alpha-tocopherol. The mixture may also contain pharmaceutically acceptable carriers and/or diluents such as polyethylene glycol. ~" The organic composition may be mixed with a suitable solvent, the metal salt mixed with a suitable solvent, and the two solutions combined in appropriate amounts to achieve the desired concentrations. The preferred metal may be added in the form of its readily available salts such as acetates, or other aliphatic acid salts, while the preferred cation, e.g. chloride, may be added in the fo.rm of its readily available salts such as sodium chloride. If complete solubilization does not occur, the mixture may be milled to obtain a fine suspension. When the formation of a metal chelate or complex is desirable, the order of mixing of ingredients and the pH may become critical, depending, on the particular complex being formed, as exempαlifieαl below. A number of specific methods for r&τy&zs&& , 2m. of particular mixtures are described in. the Examples hereof. The solvent for the organic composition will, of course, vary depending upon the particular composition. Examples of solvents for the compositions include abso¬ lute ethanol, glacial acetic acid, aqueous alkaline solutions, ethanol and dimethyl sulfoxide (DMSO) . Some of the organic compositions are also soluble in other alcohols, ether, acetone, glycerol, propylene glycol, hot water, chloroform, glycerine, polyethylene glycol, etc.. The metal solution is of a salt or a chelate of the metal and it may be a mixture of different metal salts and/or chelates containing the desired metal ions and cations. It is preferred that the salt or chelate be water soluble. The solvent for the metal will generally be an aqueous solvent. The degree of reaction between the metal and the organic composition is dependent, inter alia, upon the affinity or stability constant of the specific metal ion for the particular organic composition at the particular pH of the system. When chelates or complexes are utilized, compounds which can serve as counter-ligands are desirably provided so that discrete "molecular" entities rather than polymers of indeterminate length will form. Such counter-ligands include ethylenediaminetetraacetic acid (EDTA) , ethylene- diaminediacetic acid (EDDA), ethylenediamine, ammonia, amino acids and polyamines. A. preferred chelate is a chelate of NDGA and zinc. Such a complex may be formed byt (1) mixing a zinc salt, preferably zinc chloride, with an appropriate amount of counter-ligand to fill all available coordination sites on the zinc, as may be readily determined by one skilled in the art. For example, when EDTA or EDDA are used as counter-ligands, an equi olar amount of zinc and counter-ligand should be used. When ethylenediamine is used as the counter-ligand, a molar ratio of ethylenediamine to zinc of 2:1 should be used. When ammonia is used as the counter-ligand, a molar ratio of ammonia to zinc of 4:1 should be used. The reaction may be conducted in any suitable medium, utilizing materials in which all reactants are readily soluble. The reaction mixture may be open to the air, but an inert atmosphere is preferred. pH should be adjusted to less than about 5 with a basic material, preferably an organic base, and more preferably excess counter-ligand. Following the preparation of the zinc/counter-ligand mixture, NDGA should be added utiliz¬ ing an amount equal to half the zinc present. The pH is then further adjusted to greater than about 4 utilizing a base as described above. (2) Utilizing the same ingredients and the same proportions as described above, NDGA is first mixed with counter-ligand in an inert atmosphere with pH adjustment as described above to greater than about 6. To this mixture is added the appropriate amount of zinc salt, and the pH is adjusted to greater than about 4. Many of the organic compounds of this invention, including NDGA, are available commercially, and after purification as necessary, may be mixed with the metal salts as defined above. The following organic compounds suitable for use in this invention may be prepared by the methods described in applicant's co-pending application number 436,444, the contents of which are fully incorporated herein by reference: 1,4-bis (3,4-dimethoxyphenyl)-2,3-dimethyl butane-l,4-diol? 1,4-bis (3,4-dimethoxyphenyl)-2,3- butane; and the hydroxyphenyl variants thereof prepared by the de ethylation process described in said applica¬ tion; and d,l-NDGA. The following compounds suitable for use in this invention may be prepared by art reco nized procedures: 1-(3,4-dihydroxyphenyl) ,4-phenylbutane; 1-{3,4-dihydroxyphenyl) ,4-(3,4,5-trihydroxyphenyl) butane; l-(3,4-dihydroxyρhenyl) ,4-(2,3,4-trihydroxy- phenyl) butane; l-(3,4-dihydroxyphenyl) ,4-(2,5-dihydroxy- phenyl) butane; l-(3,4-dihydroxyphenyl) ,4-(2,4-dihydroxy- phenyl) butane; 1-(3,4-dihydroxyphenyl) ,4-(3,5-dihydroxy- phenyl) butane; l-(3,4-dihydroxyphenyl) ,4-(-2,3-dihydroxy- phenyl) butane; 1-(3,4-dihydroxyphenyl) ,4-(3-hydroxy,4- carboxylphenyl butane; l-(3,4-dihydroxyphenyl) ,4-(3,5- ditertbutyl,4-hydroxyphenyl) butane; 1-(3,4-dihydroxy- phenyl) ,4-(4-alkanylphenyl) butane; 1-(3,4-dihydroxy- phenyl) ,4-diphenylbutane; l-[4-(3,4-dihydroxyphenyl- butanyl)] polyallyl alcohol; 1-4 bis(3,4-dihydroxy- phenyl)-butyl benzene? alpha,omega-bis[4-(3,4-dihydroxy- phenyl)-butanyl]-alkan-alρha,omega-diol; 1,l-bis[4-(3,4- dihydroxyphenyl)-butanyl] alkanol; 2-(2,5-dihydroxy- phenyl) ,5-(3,4-dihydroxyphenyl) pentane; l,4-bis(3,4- dihydroxyphenyl) pentane; 1-(3,4-dihydroxyphenyl) ,6,7-di- hydroxytetralin; and diol analogs of the foregoing compounds having an OH substituent at the 4 position of the lignan chain, as well as analogs of all the foregoing having one or more hydroxy substituents on the rings replaced by methoxy substituents. NDGA tetraacetate and NDGA-tetrapropionate may be prepared by respectively adding acetylchloride or pro- pionylchloride dropwise to a cooled solution of NDGA in pyridine. Other acetates, propionates, decanoates and long-chain esters may be prepared by analogous methods and methods known to the art. Other compounds useful in this invention have been described in published literature and may be prepared by means known to the art. H. Utility. The novel mixtures of this invention are useful as antitumor agents, as antimicrobial, antiviral and anti- fungal agents, and as debriding agents for skin ulcers such as decubitus ulcers. They are useful in the treat¬ ment of herpes, and keratoses, especially actinic keratosis, and senile keratotic lesions. They are useful against a wide variety of premalignant and malignant skin tumors, basal cell carcinoma, squamous cell carcinoma and a diversified variety of melanotic lesions which are premalignant or malignant. The compositions are effec¬ tive against mammalian tumors arising from-all three - - embryonic tissue types, namely squamous cell carcinoma, e.g., lung carcinoma, arising from the ectodermal layer; adenocarcinomas, e.g., breast, renal and colon cancers, arising from the endodermal layer; melanoma and brain cancers, arising from the mesodermal layer and hematoqenous tumors. They are also useful for tne treatment of acne and warts. (As mammals may be mentioned, cat, dog, rat, horse, mouse, an monxey. Tne term "mammal" as used herein refers to- lower animals and does not include humans.) I. Dosages and Methods of Treatment. The pharmacologically active mixtures of this invention should be present in amounts ranging from about 0.5 to 100 percent of a formulation. When applied topically, the drug will be contained in a pharmaceuti¬ cally acceptable carrier, for example, a cream, ointment or solution. Polyethylene glycols are examples of suitable carriers for topical use. The frequency of application is dependent upon the conditions being -35- treataed an the strength of the preparation. Generally, the τmvtψcfvanΑ will not be applied topically more often than once daily. Generally, preferred molar ratios of the catecholic butanes to zinc with respect to two classes of tumors and exemplary application amounts/rate are shown in Table I. TABLE I Preferred Ratio Exemplary Application of Catecholic Amount/Rate of Catechol/ Treatmen /Use Butane/Zinc Zinc Composition Pre-Kalignant 1:5-5:1 Apply topically 2-150 mg/cm Tumors 1-10% cat. but./ of tumor. Repeat 15-1% zinc application when amount of prior application falls below about 5 mg/cm • Wound may be dressed until healing is complete. Healing period may extend for several months. Repeat daily Solid Epithelial 1:15-5:1 as indicated by observation Tumors of tumor εi∑e reduction 1-10% cat. but./ (i.e., if no reduction' 30-1% zinc in size after 10 days, repeat 2-3 times daily? if reduction in size is served, after 10 days, repeat at daily intervals or sooner if reduction in size ceases to continue. Healing period may extend for sever¬ al months. Alternatively, 0.1-20 ml. of composition r.ay be injected intralesion- ally at the tumor site. Typical formulations of the pharmaceutical composi ions of this invention are set forth in Table II. TABLE II Application "Form Formulatipn fPer 100 »gsιl Ointment Zinc chloride 10.0 ( (pprreeffierred range: about 0.05-35) Catecholic tmtane 5.0 ((pprreeffierred range: about 0.1-30) Peg 400 4.2 Peg 8000 61.7 Water is.o Ascorbic acid 0.1 Gel Zinc chloride 10.0 (preferred range: about 0.05-35) Catecholic butane 5.0 (preferred range: about 0.1-30) Standard denatured alcohol 10.0 Propylene glycol 22.5 Water 43.4 Non-ionic surfactant 6.0 Xant am gum 3.0 Ascorbic acid 0.1 Cream Zinc chloride 10.0 (preferred range: about 0.05-35) Catecholic butane - 5.0 (preferred range: about 0.1-30) Ascorbic acid 0.1 Benzyl alcohol 5.0 Propylene glycol 23.0 Water 25.4 Stearyl alcohol 7.0 Cetyl alcohol 4.5 White petrolatum 13.0 Poloxyl-40 stearate 7.00 Solid Zinc chloride 5.00 (preferred range: 0.05-35) Catecholic butane 5.00 (preferred range: 0.1-30) Carnuba wax 8.88 Beeswax 13.32 Lanolin anhydrous 4.44 Cetyl alcohol 4.44 Ascorbic acid 0.10 Castor oil 57.70 Water 1.20 Injec ible Liquid line suifate.TH.O 2.00 (preferred range: 0.05-35) Catecholic butane 1.05 (preferred range: 0.1-30) Water 33.94 Glycerine 36.44 Glycine 1.52 S dluε ascorbatβ 0.05 Prcpylene glycol 25.00 Sustained release topical preparations may also be used, including preparations releasing the metal salts and organic compounds at different rates. Generally for topical use, an amount of the pharma¬ ceutical preparation of this invention comprising between about 5-10 mg and about 500 mg per square centimeter of affected tissue is utilized. The area may be mechanically abraded before application of the preparation; or intra- tu or injection through the skin may be employed utilizing an amount of between about .01 ml and about 1.0 ml per cubic centimeter of estimated tumor volume. The affected area may beneficially be tape-stripped prior to applica¬ tion of the pharmaceutical preparation, and covered with a dermatological dressing after treatment. The pharmacologically active mixtures of this invention can be introduced systemically by means known to the art in dosages adjusted to the pathology and its severity. II. Zinc Potentiation of Organics for Tumor Reduction. An embodiment of this invention involves the use of zinc salts, including nitrates, sulfates, acetates and halides, preferably zinc chlorides as potentiators of tumor-reducing properties of organic compounds. As used herein, "potentiation" is meant to indicate enhancement of the ability of a given amount of organic compound to reduce or eradicate tumors or retard tumor growth over and above the ability of the same amount of organic alone to reduce tumor size. This means, in the case of organic . compounds previously known for their ability to reduce tumor size or retard tumor growth, that when the zinc salt is used in combination with such organics, a lesser dosage of organic is required to achieve the same effect. Sxamples of such compounds are epipodophyllotoxin deriva¬ tives including epipodophyllotoxin beta-D ethylidene glucopyranoside (VP-16-213; etoposide) and epipodophyllo¬ toxi beta-D thenylidene glucopyranoside (VM-26? tenipo- side " ) ; 4 , -demethylepipodophyllotoxin? mitomycin C; daunomycin; cyclophosphamide; platinum cis-diaminedi- chloride; adria ycin; allopurinol; dithranol and diethyl- stilbestrol. This potentiation also occurs in the case of organic compounds not previously known for their ability to reduce or retard tumors, but whose tumor reducing or retarding abilities alone or in combination with zinc salts fo.rm part of the subject matter of this invention. Examples of such compounds are 3-tertbutyl phenol; 4-tertbutyl phenol; p-hydroxycinnamic acid; norisoguaiacin; d,l-NDGA; NDGA; azelaic acid; l-(3,4- diacetoxyphenyl)-4-phenylbuta-l,3-diene; 1,4-bis(3,4- dihydroxyphenethyl) benzene. Some of these latter organ-ics show no activity in reducing tumor size or retarding tumor growth when used alone, and require the presence of zinc salts to potentiate their threshhold activity. The mechanism by which the zinc salt acts to poten¬ tiate the activity of organics for tumor retardation, reduction or eradication is not known, however zinc speeds penetration of the organic through the skin when it is topically applied. Zinc also causes the active organic to be retained in the skin longer than when zinc is not present. Thus for a given concentration of active organic, an effective amount can be kept at the site of skin pathology longer when a zinc salt is present than when it is not. Zinc may also aid in effecting penetra¬ tion of the organic through cell membranes. The chelating effect of zinc may also further aid in carrying oxygen- containing organics into the cells. When the chloride anion is used it may add an independent potentiating effect through super-oxide reactions into which it may enter. The amount of zinc salt needed to achieve the potentiation effect is about 0.3% to about 30% of the total amount of zinc salt and organic compound. Zinc salts alone at low concentrations, e.g. less than about 0.7% zinc chloride, have not been found to have tumor retarding or reducing activity, but smaller amounts of zinc salts have the ability to potentiate known tumor retarding and reducing organics, such as the 4*-demethyl- epipodophyllotoxins, in the sense that too low a dosage of such compounds to be active is pushed over the thresh¬ old of activity by the addition of such small amounts of zinc salts. The amount of zinc salt used must be at least enough to activate tumor-reducing activity of a lower—than- threshold dose of- organic, or an otherwise inactive organic. This amount may vary from organic compound to organic compound and will depend on the amount of organic- compound used. In the case of extremely toxic organics, where as low a dosage as possible is desired, or where a lower-than-threshold dosage of organics is required for some other reason, the least amount of zinc salt required will be the amount necessary to achieve activation. Where the organic is used at above threshold dosages, the lowest amount of zinc salt used would also be about that amount necessary to activate sub-threshold dosages. Where the organic is otherwise inactive, the lowest amount of zinc salt used would be that necessary to potentiate the smallest amount of organic capable of being so potentiated. In all cases, an upper limit of zinc salt needed is set by the amount which would cause the caustic effect of the mixture to substantially overshadow the cytotoxic effect of the organic, generally about 40% zinc salt concentration. It is generally preferred that the dosage of the organic compound be 03805 _ 4Q _ optimized, and the ratio of zinc salt to organic used should be at least equal to that required for potentiation of the lowest possible dosage of the organic. In general, the preferred amount of zinc salt, preferably zinc chloride, in accordance with the foregoing discussion is between about 1 and about 30 weight percent of the total preparation. Although other materials may be present in a pharmaceutical preparation containing an active organic and zinc salt, such as viscosity adjusters, stabilizers, preservatives, and the like, it is preferred that such additives not significantly compete with the active organic compound in providing coordination sites for the zinc ions. III. Organic Tumor Reducing Compounds. The compositions according tothe invention, particularly nordihydroguaiaretic acid and related compounds, in preparation suitable for topical application or intratumor injection have been found to be e fective at certain concentrations in reducing or eradicating tumors and/or stopping tumor growth. It has been found, surprisingly, that although- NDGA stimulates tumor growth at low concentrations and is extremely toxic in concentrations high enough to cause tumor eradication after systemic administration, e.g. intraperitoneally or intravenously, effective concentra¬ tions can be administered without significant toxicity topically, and even by injection into tumors whose vascular blood supply connects to the rest of the organ¬ ism, without significant toxicity. This compound appears to be selectively taken up and utilized by the tumor cells and possibly rapidly detoxified as it leaves the tumor bed. Similarly, the compositions according to the invention havebeen found to be effective andnon-toxic orthe treatment of theother treatments and diseases disclosed herein. NDGAconcentrations between about 4.0 and about 18.0 weightpercent are effective against tumors when used topically or injected directly into the tumor. Higher concentrations, of about 8.8 to about 18 percent are preferred, with about 16 to about 18 percent being most preferred. The medicinal preparation should be dispersed in a suitable pharmaceutical carrier of sufficient viscosity to allow spreading of the preparation and good adherence to the membrane to which it is topically applied. A less viscous carrier, allowing injection via hypodermic syringe, is required when the preparation is to be injected into the tumor mass. Many suitable carriers are known to the art. A mixture of polyethylene glycols of about 400 and about 3350 molecular weight, adjusted to the desired viscosity has been found to be effective. NDGA and its isomers, e.g. both eso and d,l-NDGA, as well as analogs such as norisoguaiacin, dihydro¬ guaiaretic acid, 1-(3,4-dihydroxyphenyl)-2,3-dimethyl, 4-(3-methoxy,4-hydroxyphenyl) butane, 3'demethoxyiso- guaiacin, and other compounds naturally occurring in Larrea, and pharmaceutically acceptable salts thereof . with cations as defined above, are effec'tive for use as described above, both with and without metal, e.g., zinc, ions , . With and without the presence of metal ions, " he preferred catecholic butanes useful in the compositions of the instant invention are of the Formula wherein R. and R- are independently H, lower alkyl or lower acyl; R- R, f Rg and R £ are independently H or lower alkyl; R.,, Rg and R Q are independently H, hydroxy, lower alkoxy or lower acyloxyj R 10' R ll* R 12' an< R 13 are i nae P enα"ent 2.Y H or lower alkyl. Lower alkyl is intended to generally mean C.-C- alkyl, and preferably R^ and R^ are C j - C^ alkyl. Lower acyl is -In¬ tended to generally mean tC^-Cg] " acyl, with tC 2 - C fi ] being * preferred. It will be appreciated by those skilled in this art that Formula II is directed to both the phenolic compounds and the conventional esters and ethers thereof. Illustrative classes of compounds within the scope of Formula (II) are those wherein: a) one or more R,, R-, R 3 , 4 , R-., R g , R 7 , R g , R_ , R 1Q , R, , , R i ' and R 13' are H ' e * < 3*' those wherein R 5 , is H, R and R g are H or R-. R g and R- are H and g and R g are OH or OR,; b) 3B and 4 each are CE or C 2 H-. including those of a) , especially those wherein R_ , R g , and R_ are H and/or R g and Rg are OH and OR, ; c) R, and R 2 are lower acyl, e.g., hydrocarbonacyl preferably, alkanoyl, e.g., acetyl, propionyl, etc., in¬ cluding those of a) and b) ; d) R, and R 2 are alike and Rg and R g are OR, including those of a) , b) and c) ; and e) The compound is in the form of a single optical isomer or a mixture of such isomers, e.g., a racemic mixture or diastereoisomers including each of a) , b) , c) , and d) . As used herein, lower alkyl represents, inter alia, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, and the like. Lower acyl represents groups having the general formula RC0-, e.g., acetyl (CH 3 C0-) , propionyl {CΕ. ZΕ. Z0-) , butyryl (CH 3 CH 2 CH 2 CO-) , and the like. When the catecholic butane compound is named as a substituted phenyl, the corresponding groups are acetoxy (CH 3 C0 2 -) , propionyloxy (CH 3 CH 2 C0 2 -) , and butyroyloxy (CH 3 CH 2 CH 2 CO-) . Other useful compounds include 3-tertbutylphenol; 4-tertbutylphenol; p-hydroxycinnamic acid? norisoguaiacin? d,1-NDGA; 1-(3,4-diacetoxyphenyl)-4-phenylbuta-l,3-diene? and l,4-bis-(3,4-dihydroxyphenethyl) benzene. Additionally, certain aliphatic acids are useful as described above. Straight-chain acids of 6 or more carbons, preferably hav.ing carboxyl groups at both ends of the chain, are effective against solids tumors in mammals, including human breast tumors, when applied topically or by intratumor injection. A preferred class of such dicarboxylic aliphatic compounds comprises alpha,omega-dicarboxylie acids, preferably C, to C,. dicarboxylic acids, and most prefer¬ ably azelaic and dodecandioic acids. Such dicarboxylic acids are exemplified by: H00C-(CH 2 ) 5 -COOH; H00C-(CH 2 )g- COOH; HOOC-(CH 2 ) 7 -COOH; HOOC-(CH 2 ) g -COOH; HOOC-(CH 2 ) g - COOH; HOOC-(CH 2 ) 10 -COOH? HOOC-<CH 2 ) ? 1;1 -COOH and HOOC- (CH 2 ) 12 -COOH. The following examples are included by way of illustration and not by way of limitation. Unless otherwise indicated, the nordihydroguaiaretic acid used in the instant Examples was the meso-isomer and is designated NDGA. Other iso ers are indicated, e.g., d,l-NDGA. EXAMPLE I The catecholic butane l-(3,4-dihydroxyphenyl)-4-(2,3,4 -trihydroxyphenyl) butane was prepared by the following procedure. 500 grams of 3,4-dimethoxydihydrocinnamic acid was suspended in 1.6 liters of methanol containing 25fl ml of 2,2τdimethoxypropane. To this mixture was added dropwise a solution made by adding 20 ml. of acetyl chloride to 400 ml of methanol. The resulting mixture was stirred overnight at room temperature and finally at reflux for one hour. The solvent was evaporated to give a syrup in quantitative yield, 533 g. To 912 ml. of lithium aluminum hydride (1M in THF) was added dropwise 213 g. of 3,4-dimethoxydihydrocinnamic acid methyl ester dissolved in 900 ml of dry THF at such a rate as to maintain gentle reflux (5 hours). The reaction mixture was stirred overnight at room temperature, cooled in an ice bath and treated dropwise with ammonium chloride solution (saturated) (104 ml) over a two hour period. After stirring for several hours, the reaction mixture was diluted with 500 ml. of THF, filtered and the filtrate evaporated in a vacuum to give 160 g. (86%) of a light yellow oil. 3-(3,4-dimethoxyphenyl) propanol (202 g) was added to 218 ml of triethylamine in one and half liters of methylene chloride. This solution was cooled to -10°C in an ice salt bath and 87.6 ml. of methanesulfonyl chloride was added dropwise over a one and a half hour period while stirring rapidly. Stirring was continued for another hour and the mixture was washed with 700 ml. of ice water, 700 ml. of 3N hydrochloric acid, 700 ml. of saturated sodium bicarbonate and finally with 700 ml. of brine. The organic phase was dried with sodium sulfate and evaporated in a vacuum to give an orange oil in quantitative yield, 282 g. 3-(3,4-dimethoxyphenyl) propanol ethanesulfonate, 282 g., (1.029 mol.); KBr, 282 g. (2.37 mol.) and dicyclohexano-18-crown-6, 19.2 g. (0.01515 mol.) were stirred in refluxing acetonitrile, 2.8 liters (dried over 3A molecular sieves) for 22 hours. The mixture was filtered and the filtrate evaporated in a vacuum to give an orange oil, 267 g. The product could be purified by vacuum distillation at 0.5 mm Hg, b.p.=113-116 β C. 3-(3,4-Dimethoxyphenyl) propyl bromide, 25.9 g., in 50 ml. of dry tetrahydrofuran (dried distillation from LAH) was placed in a dropping funnel. Magnesium powder, 2.5 g., and a trace of iodine was placed in a dry three neck flask with nitrogen inlet and reflux condenser. The reaction started upon addition of the liquid reactant and reflux was continued over a three hour period during which time the metal dissolved in the stirred solution. The reaction was cooled and the volume made up to 200 ml. to form a 0.5M solution in dry THF. 2,3,4-Trimethoxybenzaldehyde, 1.96 g. (0.01 mole), dissolved in 20 ml. of dry THF and 20 ml. of the 0.5M Grignard reagent from 3-(3,4-dimethoxyphenyl)propyl bromide in THF was added dropwise at ice temperature. The mixture sat over night at room temperature. The solution was evaporated in a vacuum and 20 ml. of ethanol was added carefully followed by excess sodium borohydride. Refluxing for a few minutes destroyed the yellow color of the small amounts of ketone and other unsaturated impurities formed from oxidation of the product. Most of the ethanol was evaporated and the residue partitioned between water and ether, 50 ml. of each. The ether phase was dried over sodium sulfate and evaporated to give 4.65 g. of a pale yellow oil. The 4-(3,4-dimethoxyphenyl)-l-(2,3,4-trimethoxyphenyl) butanol, 3.65 g. was treated with excess sodium hydride, 1 g., and methyl iodide, one ml, in 25 ml. of dry dimethylforma ide during one hour of stirring. Water was added carefully dropwise at first and finally 500 ml. of water was added. The product was extracted three times with 50 ml. of chloroform and the solvent evaporated to give a colorless crude oily product that can be used in the next step without further purification. About 100 mi- of anhydrous ammonia was condensed into a three necked flask with a dry ice condenser and dry ice bath. The flask was protected from moisture with a soda-lime tube and flow of dry nitrogen. One gram of clean sodium metal was dissolved in the liquid ammonia and the whole of the crude product in 20 ml of dry tetrahydrofuran was added as quickly as possible. The dark blue solution was stirred rapidly for twelve minutes before enough methanol was added to destroy the blue color. Evaporation of the solvent under a vacuum gave a thick residue to which 500 ml. of water was added. The water solution was extracted twice with 50 ml. of chloroform that left three grams of oily residue on evaporation. Chromatography of this crude product on 300 g. of silica-gel using chloroform as an eluate gave 2.3 of pure l-.(3,4-dimethoxyphenyl)-4-(2,3,4- trimethoxyphenyl) butane (one spot on TLC). A 1.15 g. sample of l-(3,4-dimethoxyphenyl)-4-(2,3, 4- trimethoxyphenyl) butane was refluxed for nine hours in 50 ml. of 48% hydrobromic acid under an inert nitrogen atmosphere. Standing over the weekend allowed 641 mg. of tan product to settle out in the freezer. This material was recrystallized under inert atmosphere from methanol-water 1:20 to give light pink crystals, m.p.=165-167 β C. The following compounds were prepared by a similar procedure: a) 1-(3,4-Dihydroxyphenyl)-4-(3,4,5- trihydroxyphenyl)butane; b) 1-(3,4-Dihydroxyphenyl)-4-phenylbutane c) l- ( 3 , 4-Dihydroxyphenyl-4-(2,5-dihydroxyphenyl) butane ; d) 1,4-Di(3,4-dihydroxphenyl)-l,2,3,4-tetramethylbutane e) 1,4-Di{3 ,4-dihydroxyphenyl)-2-methyl-3-ethylbutane ) 1,4-Di(3,4-dihydroxyphenyl)-l-propyl-2-methyl-3- ethylbutane EXAMPLE 2 To liquid ammonia (approximately 150 ml.) was added powdered ferric chloride, 150 mg., then small pieces of sodium, 1.53 g., were added and the blue color was allowed to dissipate over about a 20 minute period. Tθ- the resulting grey suspension of sodamide was added solid 3,4-dimethoxypropiophenone, 11.64 g., in small portions and the mixture was stirred for about five minutes. Solid alpha bromo-3,4-dimethoxy-propiophenone, 16.38 g., was then added in small portions to the grey- green mixture. After the mixture stirred for one hour 8. g. of ammonium chloride and 150 ml. of dichloromethane was added. The ammonia was allowed to evaporate and the mixture filtered while the solid residue was extracted twice with additional dichloromethane. Evaporation of the solvent to a small volume and dilution with methanol allowed crystallization of 19.75 g. of product'. The 2,3-bis(3,4-dimethoxybenzoyl)butane, 1.65 g., was not soluble in toluene, 25. ml, so enough dry tetrahydrofuran, 25. ml, was added to make the solution complete. An excess, 5. ml, of sodium dihydrobis(2- methoxyethoxy)aluminate (Vitride- 70% in toluene) was added and stirred at room temperature for several days. A saturated solution of sodium sulfate was added and the some cases, the tumors were injected with the test compound or the control. Almost all of the tumors demonstrated a significant reduction in size or were completely eliminated by the test compounds containing zinc chloride and NDGA. Exemplary compositions of the mixtures are given in Table 2: Table 3 Mixture ZnCl 2 NDGA EDTA H 2 0 PEGO 53 27.5 . 6.9 14.7 18.3 32.6 54 28 6.8* 14.7 18.2 32.9 55 16.4 6.9 8.6 18.0 32.2 * d, 1 NDGA These mixtures were tested for their potential antitumor activities against B-16 melamonas grown in mice in accordance with the procedure discussed above. The results are given in Table 2a. Table- 3a Tumor Size % Clear % Survival Mixture n (Control) (Control) (Control) 53 10 80 80 (575+270) ( 0 ) ( 60 ) 53 10 8 51±118 70 100 (711+286) ( 0 ) ( 100 ) 54 10 60 100 (711+286) ( 0 ) ( 100 ) 55 10 73 522+356 10 100 (711+286) ( 0 ) ( 100 ) EXAMPLE 4 Fifteen older dogs having perianal adenomas were treated topically with the NDGA plus zinc salt ointment having a strength of 55% (w/w) . To 36.7 grams of powdered Larrea divaricata extract,- containing 85% of weight NDGA, were added 24.5 grams of powdered rosehips and the mixture was mixed in a blender for 5 minutes. The blended mixture was then mixed with 100 milliliters of an aqueous solution containing 185.9 grams zinc chloride to form a paste. The paste was allowed to stand at room temperature for 24 hours. Thereafter, it was stirred and then placed in a screw- capped glass container. The container was placed in a humidified oven at 40°C for 5 days. This incubated paste was then suspended in 500 milliliters of water and shaken at room temperature for 24 hours on a reciprocating shaker. The zinc chloride extract solution was then evaporated to near dryness on a rotary evaporator at 90 β C under reduced pressure. A sufficient quantity of this dried zinc chloride extract was added to 120 grams- of an ointment base consisting of 10% (w/w) stearyl alcohol and 90% (w/w) polyethylene glycol to ■ obtain an ointment containing 70% (w/w) of the extract. The normal treatment for such a condition is surgery; however, these older dogs were poor surgical risks. The tumor of each dog was biopsied and the ointment was applied topically into the biopsied incision. The duration of treatment varied depending upon the severity of the adenoma. Dogs with simple circumscribed adenomas required only one treatment. The dogs with more advanced adenomas generally required more than one treatment which were given three to five days apart. The treatment was successful in thirteen of the fifteen dogs. The treatment was not successful in two of the dogs which had extremely advanced cases of perianal adenomas. EXAMPLE 5 Test compositions were prepared according to the following general method to test the activity of the compositions according to the invention against human breast adenocarcinoma, MX-1. The NDGA, BHT (butylated hydroxytoluene), and Pego 400 were measured and mixed together with heating until melted and dissolved. Pego Base (50% Pego 400, 45% Pego 3350 and 5% stearyl alcohol) was prepared by mixing and heating the components together in a separate container until they dissolved. ZnCl- and EDTA were dissolved in water with heating and stirring in a separate container. The ingredients in each of the separate containers were added together in amounts needed to give the ccaHse (glioma); melanoma; and colon cancer, CX-1. The test composition with the approximate wt/wt percentages given below was prepared according to the procedure previously described in Example 4. The control composition was Pego 400. Inαredient Test Composition 1 Control BHT 0.16 EDTA 2.10 NDGA 0.66 ZnCl 2 4.26 H 2 0 2.62 Pego Base 1.43 Pego 400 88.77 100 The composition was then tested for its effect on human tumors of varying origin implanted in athymic mice as previously described. Generally, there were ten mice in each group tested with Pego 400 control. Instances in which the number of mice varied are specifically indicated. Results are given in Table 7. TABLE 7 Tumor ■ Tumor Test Free at Premature At Tumor Type 60 .Pay.s_ eath Death Recur fence. LX-1 1 8 0 2 0 ( lung) control. 0 0 5 0 MX-1 r 8 0 2 1 (breast) confcrco . 0 0 2 0 RX-1 Z 8 1 1 0 (Renal) control 0 1 5 0 Glioma r 6 0 0 0 (Brain) cαrr-trα! 0 0 2 0 Melanoma 1 10 0 0 0 control 0 0 5 0 CX-1 1 8 1 2 0 (Colon) central 0 0 5 0 EXAMPLE 8 A number of catecholic butane compositions were formulated into- test compositions according to- the following general method, and tested for activity against human breast adenocarcinoma, MX-1. Zinc chloride was dissolved in Pego 400 to prepare a stock solution. The amount of organic compound required to give the final concentration given below was separately dissolved in Pego 400. The two solutions were mixed to give a final concentration in each test composition of zinc chloride at 0.69 wt/wt % and each organic compound at a molar concentration equivalent to 4.4 wt/wt % of NDGA. The test compositions in Table 7 were tested for their effectiveness as antitumor agents against xenografts of the human breast adenocarcinoma, MX-1, grown in athymic mice. They were administered to five animals by intratumor injection. Animals were administered 0.05 ml of test composition unless indicated otherwise. TABLE 8 Animal Tumor Free Premature Tumor Tumor Qrga ς Compounds 5Q. Pays Death at peath Recurrence Pego control 0 0 5 0 NDGA 4 1 0 0 d,l NDGA 5 0 0 0 NDGA Tetracetate 4 0 1 0 NDGA 4 0 i 1 Tetrapropionate l,4-bis(3' -methoxy-4' -hydroxyphenyl Butane l,4-bis{3' -methoxy-4' -hydroxyphenyl)-2, 3-dimethyl butane l-(3* ,4'-dihydroxyphenyl) -4-(2" ,3" ,4'-trihydroxy- phenyl)-butane l-(3' ,4'-dihydroxyphenyl) -4(3' ,4' ,5'-trihydroxy- phenyl)-butane l-(3' ,4' ,-dihydroxyphenyl) -4-(2' ,5'-dihydroxyphenyl) -butane l-(3' ,4'-dihydroxyphenyl) -4-phenyl butane l-(3' ,4'-dihydroxphenyl) -4-(2 ' ,4 '-dihydroxyphenyl) -butane EXAMPLE 9 Various zinc salts were tested in combination with NDGA to determine, the ef ectiveness of the compositions according to. the invention against xenografts of human breast adenocarcinoma, MX-1, grown in groups of five athymic mice. The tumors were implanted subcutaneously in the left flank of the mice and the tumors were allowed to grow until they reached an approximate size of between 25 and 100 mm (length x width). The mice were given a single 0.010 ml intratumor injection of the test composition. The concentration of the various metal salts in the test compositions was 0.73% (wt/wt) metal salt and 1.0% (wt/wt) NDGA, in a PEGO 400 base. The results of these test compositions are summarized in Table 8. TABLE 9 Tumor Tumor Free at Premature at Tumor Test ComDound 60 Days Death Death Recurrence ZnCl 2 4 0 3 3 ZnS0 4 ' 7H 2 0 2 0 3 3 ZnBr 2 2 0 3 3 Zn Acetate * 2H 2 0 2 0 3 3 Zn(N0 3 ) 2 .6H 2 0 3 1 1 1 ZnCl- (without NDGA) 1 0 19 19 In a separate trial, solubilized zinc gluconate demonstrated efficacious results in the jj vitro inhibition of clonogenic human lung tumor cells (LX-T) when combined with NDGA. EXAMPLE 10 This example describes the antineoplastic activity of co positions containing NDGA and zinc ions in clinical studies on human patients with basal cell epithelio a. Compositions, as set forth in Table 9 suitable for topical application were prepared: TABLE 10 Composition ComDounds A B C D E zinc chloride 29.8 1.0 5.0 10.0 20.0 NDGA 4.6 4.6 4.6 4.6 4.6 EDTA 14.7 0.49 2.47 4.93 0 BHT 1.1 1.1 1.1 1.1 0 stearyl alcohol 0.5 0.5 0.5 0.5 0.5 H 2 0 18.3 18.3 18.3 18-.3 18.3 Pego 400 26.4 26.4 26.4 26.3 26.4 Pego 3350 4.5 4.5 4.5 4.5 4.5 The water was heated to about 80-90°C with stirring, and zinc chloride was added. The EDTA was next added with mixing until dissolved. In a separate container the polyethylene glycol 400 was heated to about 80-90°C with stirring, the NDGA was added thereto, then the BHT, and this mixture was added to the zinc chloride-EDTA solution with stirring. The entire mixture was then cooled to about room temperature and passed through a number 3 roller mill until smooth. The polyethylene glycol 3350 was then heated to about 80-90 β C and the milled ingredients added thereto with mixing. The surface of the lesions were tape stripped prior to each application. The test medication was applied directly to the lesion with a coating approximately 2mm thick, and covered with a dressing. After a minimum of seven (7) days, a second application was applied at the discretion of the investigator. The dose ranged from 20-350 mg/cm 2 with as much as 500 mg/cm2 utilized for deep tumors.- To determine the effect of the test compound on " the malignant neoplasma, an excisional biopsy was obtained 30 days after the initial treatment. Of the fifty seven patients with basal cell epithelioma who were treated with compositions A, B, C or D, twenty showed negative biopsies, i.e., no evidence of tumor, at the conclusion of the treatment period. EXAMPLE 11 Fifty-nine (59) human patients with actinic keratosis were treated with NDGA plus zinc containing compositions B, C, or D as in Example 9. The test medication was. applied directly to the lesion with a coating of approximatley 2 mm and confined to the lesion margin. A dressing was applied to the lesion. A visual examination and measurement of the lesion was performed 7 and 14 days following the initial treatment. At the discretion of the investigator, a second treatment with the same test compound was applied. In order to determine whether the test compound eradicated the premalignant neoplasm, a punch biopsy was obtained 30-60 days after the initial treatment. If the biopsy report was negative, i.e., no tumor, the patient was examined every 6 months for a period of 12 months. If the biopsy continued to show evidence of actinic keratosis, the patient was withdrawn from the study and treated with conventional therapy. The fifty nine (59) patients had a total of 61 lesions. After treatment with the NDGA plus zinc salt compositions, thirty two of the lesions showed negative biopsies, i.e., there was no evidence of actinic keratosis. EXAMPLE 12 Canine patients with various tumor lesions were treated with compositions A, C, D or E of Example 9. The animals were restrained from movement for two hours physically or with sedatives (e.g. 0.03 mg oxymorphone/lb.sq with atropine sulfate). After clipping, washing and measuring the tumor size, the skin surface was abraded until bleeding occurred. To enhance the penetration of the test compositions for large or subdermal tumors, a 20 or 22 gauge needle was used to puncture the tumor. After blotting the skin dry of blood, the tumor site was covered with a 1-2 mm coating of the test composition extending 5 mm peripherially. After 2 hours, ' the compound was wiped off and the area gently cleansed. The test composition was applied up to three times within a two-week interval or until the tumor cleared. The results of the canine studies are given in Table 11, and show that in canine patients, seven of the twenty four animals showed complete remissions, and another four showed partial remission. concentrations desired and allowed to cool with vigorous mixing. Any further dilution to achieve desired wt/wt % was achieved by adding Pego 400. When an ingredient was omitted from a particular composition, the amount of the missing ingredient was supplied by adding additional Pego ' 400. Wt/wt % of compositions utilized in this experiment are given below. Test Composition Ingredient in wt/wt % 1 2 3 ZnCl 2 4.3 4.3 4.3 Purified water 2.6 2.6 2.6 EDTA - 2.1 2.1 NDGA 0.66 0.66 0.66 BHT 0 0.66 0 Pego 400 91.04 88.28 88.94 Pego Base 1.4 1.4 -.1.4 The test compositions were tested in five athymic mice implanted with human breast adenocarcinoma, MX-1. Results are given in Table 4 and confirm the activity of. these combinations of the phenolic butane, NDGA, and zinc ions. TABLE 5 Test Tumor Free Premature Tumor Tumor Composition at 60 days Death at Death Recurrence 1 4 1 0 0 2 4 0 1 1 3 5 0 0 0 EXAMPLE 6 In order to demonstrate the activity and use of zinc ions from other salts, two test compositions were prepared according to the procedure previously described. In these, the zinc chloride was replaced by zinc iodide and zinc bromide. Concentrations of the ingredients are given below in wt/wt percent. Test Composi i -an Inαredient 1 2 BHT 0.65 0.72 EDTA 2.1 2.3 NDGA 0.98 1.1 Znl 2 3.9 — ZnBr 2 4.3 H 2 0 2.6 2.9 Pego Base 1.4 0 Pego 400 88.37 88.68 The two compositions were tested for antitumor activity against human breast adenocarcinoma, MX-1, grown in five athy ic mice as previously described. The results are given in Table 5. TABLE 6 Test Tumor Free Premature Tumor Tumor Composition at 60 days Death at Death Recurrence 1 4 1 0 0 2 4 0 1 0 EXAMPLE 7 A test composition of NDGA plus zinc chloride was ' investigated for and found to possess antineoplastic activity against xenografts of the following human cancers: lung squamous cell carcinoma, LX-1; breast adenocarcinoma, MX-1; renal cell cancer, RX-1; brain cancer (glioma); melanoma; and colon cancer, CX-1. The test composition with the approximate wt/wt percentages given below was prepared according to the procedure previously described in Example 4. The control composition was Pego 400. Inqredient Test Comoosition 1 Control BHT 0.16 EDTA 2.10 NDGA 0.66 ZnCl 2 4.26 H 2 0 2.62 Pego Base 1.43 Pego 400 88.77 100 The composition was then tested for its effect on human tumors of varying origin implanted in athymic mice as previousl described. Generally, there were ten mice in each group tested with Pego 400 control. Instances in which the number of mice varied are specifically indicated. Results are given in Table 7. TABLE 7 Tumor Tumor Test Free at Premature At Tumor ,TϊPS Cou esUion. GO Pays Death ____ Efic rrence LX-1 1 8 0 2 0 (lung) control 0 . 0 5 0 MX-1 1 8 0 2 1 (breast) control 0 0 2 0 RX-1 1 8 1 1 0 (Renal) control 0 1 5 0 Glioma 1 e 0 0 0 (Brain) control 0 0 2 0 Melanoma 1 10 0 0 0 control 0 0 5 0 CX-1 1 8 1 2 0 (Colon) control 0 0 5 0 EXAMPLE 8 A number of catecholic butane compositions were formulated into test compositions according to the following general method, and tested for activity ' against human breast adenocarcinoma, MX-1. Zinc chloride was dissolved in Pego 400 to prepare a stock solution. The amount of organic compound required to give the final concentration given below was separately dissolved in Pego 400. The two solutions were mixed to give a final concentration in each test composition of zinc chloride at 0.69 wt/wt % and each organic compound at a molar concentration equivalent to 4.4 wt/wt % of NDGA. The test compositions in Table 7 were tested for their effectiveness as antitumor agents against xenografts of the human breast adenocarcinoma, MX-1, grown in athymic mice. They were administered to five animals by intratu or injection. Animals were administered 0.05 al of test composition unless indicated otherwise. TABLE 8 Animal Tumor Free Premature Tumor Tumor Orαanic Compounds £2. Days Death Ai_ Death B.?c:urrenct Pego control 0 0 5 0 NDGA 4 1 0 0 d.l NDGA 5 0 0 0 NDGA Tetracetate 4 0 1 0 NDGA 4 ' 0 i 1 Tetrapropionate 1,4-bis(3* -methoxy-4' -hydroxyphenyl Butane l,4-bis(3* -methoxy-4' -hydroxyphenyl)-2, 3-dimethyl butane l-{3' ,4*-dihydroxyphenyl) -4-(2 , ,3' ,4*-trihydroxy- phenyl)-butane l-(3" ,4*-dihydroxyphenyl) -4(3' ,4* ,5'-trihydroxy- phenyl)-butane l-(3' #4' ,-dihydroxyphenyl) -4-(2',5'-dihydroxyphenyl) -butane l-(3* ,4*-dihydroxyphenyl) -4-phenyl butane l-(3' ,4'-dihydroxphenyl) -4-(2' ,4'-d ydroxyphenyl) -butane EXAMPLE 9 Various zinc salts were tested in combination with NDGA to determin the effectiveness of the compositions according to the invention against xenografts of human breast adenocarcinoma, MX-1, grown in groups of five athymic mice. The tumors were implanted subcutaneously in the left flank of the mice and the tumors were allowed to grow until they reached an approximate size of between 25 and 2 100 mm (length x width). The mice were given a single 0.010 ml intratumor injection of the test composition. The concentration of the various metal salts in the test compositions was 0.73% (wt/wt) metal salt and 1.0% (wt/wt) NDGA, in a PEGO 400 base. The results of these test compositions are summarized in Table 8. TABLE 9 Tumor Tumor Free at Premature at Tumor Test Compound 60 Days Death Death Recurrence ZnCl 2 4 0 3 3 ZnS0 4 * 7H 2 0 2 0 3 3 ZnBr- 2 0 3 3 Zn Acetate * 2H,0 2 0 3 3 Zn(N0 3 ) 2 .6H 2 0 3 1 1 1 ZnCl 2 (without NDGA) ) 1 0 19 19 In a separate trial, solubilized zinc gluconate demonstrated efficacious results in the in. vitro inhibition of clonogenic human lung tumor cells (LX-T) when combined with NDGA. EXAMPLE 10 This example describes the antineoplastic activity of compositions containing NDGA and zinc ions in clinical studies on human patients with basal cell epithelioma. Compositions- as set forth in Tabϊe 9 suitable for topical application were prepared: TABLE 1.0 Composition Compounds A B C D E zinc chloride 29.8 1.0 5.0 10.0 20.0 NDGA 4.6 4.6 4.6 4.6 4.6 EDTA 14.7 0.49 2.47 4.93 0 BHT 1.1 1.1 1.1 1.1 0 stearyl alcohol 0.5 0.5 0.5 0.5 0.5 H.O 18.3 18.3 18.3 18.3 18.3 Pego 400 26.4 26.4 26.4 26.3 26.4 Pego 3350 4.5 4.5 4.5 4.5 4.5 The water was heated to about 80-90 β C with stirring, and zinc chloride was added. The EDTA was next added with mixing until dissolved. In a separate container the polyethylene glycol 400 was heated to about 80-90 β C with stirring, the NDGA was added thereto, then the BHT, and this mixture was added to the zinc chloride-EDTA solution with stirring. The entire mixture was then cooled .to about room temperature and passed through a number 3 roller mill until smooth. The polyethylene glycol 3350 was then heated to about 80-90 β C and the milled ingredients added thereto with mixing. The surface of the lesions were tape stripped prior to each application. The test medication was applied directly to the lesion with a coating approximately 2mm thick, and covered with a dressing. After a minimum of seven (7) days, a second application was applied at the (discretion of the investigator. The dose ranged from 2 2 23-350 mg/c with as much as 500 mg/cm utilized for deep tumors.-. To determine the effect of the test compound on the malignant neoplas a, an excisional biopsy was obtained 30 days after the initial treatment. Of the fifty seven patients with basal cell epithelioma -who were treated with compositions A, B, C or D, twenty showed negative biopsies, i.e., no evidence of tumor, at t e conclusion of the treatment period. EXAMPLE 11 Fifty-nine (59) human patients with actinic keratosis were treated with NDGA plus zinc containing compositions B, C, or D as in Example 9. The test medication was applied directly to the lesion with a coating of approximatley 2 mm and confined to the lesion margin. A - dressing was applied to the lesion. A. visual examination and measurement of the lesion was performed 7 and 14 days following the initial treatment. At the - discretion of the investigator, a second treatment with the same test compound was applied. In order to determine whether the test compound eradicated the premalignant neoplasm, a punch biopsy was obtained 30-60 - days after the initial treatment. If the biopsy report was negative, i.e., no tumor, the patient was examined every 6 months for a period of 12 months. If the biopsy continued to show evidence of actinic keratosis, the patient was withdrawn from the study and treated with conventional therapy. The fifty nine (59) patients had a total of 61 lesions. After treatment with the NDGA plus zinc salt compositions, thirty two of the lesions showed negative biopsies, i.e., there was no evidence of actinic keratosis. EXAMPLE 12 Canine patients with various tumor lesions were treated with compositions A, C, D or E of Example 9. The animals were restrained from movement for two hours physically or with sedatives (e.g. 0.03 mg oxymorphone/lbc.sqr with atropine sulfate). After clipping, washing; and measuring the tumor size, the skin surface wss abraded until bleeding occurred. To enhance the penetration, of the test compositions for large or subder al tumors,, a 20 or 22 gauge needle was used to puncture the tumor. After blotting the skin dry of blood, the tumor site was covered with a 1-2 mm coating of the test composition extending 5 mm peripherally. After 2 hours, the compound was wiped off and the area gently cleansed. The test composition was applied up to three times within a two-week interval or until the tumor cleared. The results of the canine studies are given in Table 11, and show that in canine patients* seven of the twenty four animals showed complete remissions, and another four showed partial remission. -63- TABLE 12 No. Test Animal Partial NO Composition Tested CjJLXft Effec . Effect Mast cell tumors A 3 1 1 1 Mast cell tumors CD 6 - 2 A Mast Cell tumors ε 2 1 - 1 Squamous cell carcinoma A 1 1 - - Mammary Adenoma A 2 1 - 1 Perianal Adenoma A 7 1 1 5 Perianal Adenitis A 1 - - 1 Perianal Cyst (Benign) A 1 1 - Basal Cell Carcinoma A 4-1 -1 4-Z — Totals 24 7 4 13 EXAMPLE 13 Equine patients with various tumor lesions were treated with compositions A, C, D, or E of Example 9. Melanoma, sarcoid and squamous cell carcinoma lesions were removed to skin level by surgical debulking; for papillomas, the lesion tips were removed. After he ostasis, the tumor site was covered liberally with the test compound extending 5 mm peripherially. Two weeks later, the crust was removed, the lesion area abraded and the test compound applied topically. After an additional two weeks, any crust was again removed from the lesion and the area abraded. The same test compound was again applied topically. Four weeks later, a biopsy of the lesion area was performed. The results of the equine studies in Table 12, show that NDGA plus zinc salt compositions show good activity against the tumor lesions in equine patients. The high activity of the composition against Papillomas, known to have viral -70- co ponents, indicated the activity of these compositions-. TABLE 13 No. Test Animals Lesion Composition Tested Cure Partial No Effect Papillomas A 4 4 - • - Melanoma . A 4 3 - 1 Squamous A 3 2 1 - Cell Car. Sarcoid A 5 4 1 - Sarcoid C or D 6 1 2 3 Sarcoid ε -5. " _& —Ξ- — 27 19 4 4 EXAMPLE 14 The i vivo antitumor effect of the interaction of NDGA and ZnCl, at various ratios was determined against MX-1 (human breast adenocarcinoma) cells. Male or female athymic Balb/c mice, six to eight weeks of age and weighing 20 to 35 grams were used. MX-1 cells were cultured in the standard RPMI-1640 media and implanted subcutaneously in the flank of the nude mice in order to propagate the tumor line. Nude mice were implanted with 25 mg of the MX-1 solid tumor fragments. Tumors which reached the 25-100 mm range were used for the experiment. 0.1 ml of the test compound was injected directly, into the tumor. The tumors were measured periodically to determine their weight calculated by using half the product of the length times the width times the height of the tumor. The procedure was repeated at regular intervals until 60 days after components, indicated the activity of these compositions. TABLE 13 NO. Test Animals Lesion Composition. Tested., Cure P.sr,t.ial NO Effect Papillomas A 4 4 - - Melanoma A 4 3 - 1 Squamous A 3 2 1 - Cell Car. Sarcoid A 5 4 1 - Sarcoid C or D 6 1 2 3 Sarcoid E -1 _a — — z. 27 19 4 4 EXAMPLE 14 The JLn, vivo antitumor effect of the interaction of NDGA and ZnCl- at various ratios was determined against MX-1 (human breast adenocarcinoma) cells. Male or female athymic Balb/c mice, six to eight weeks of age and weighing 20 to 35 grams were used. MX-1 cells were cultured in the standard RPMI-1640 media and implanted subcutaneously in the flank of the nude mice in order to propagate the tumor line. Nude mice were implanted with 25 mg of the MX-1 solid tumor fragments. 2 Tumors which reached the 25-100 mm range were used for the experiment. 0.1 ml of the test compound was injected directly into the tumor. The tumors were measured periodically to determine their weight calculated by using half the product of the length times the width times the height of the tumor. The procedure was repeated at regular intervals until 60 days after the initial treatment or all mice had died. Mice which showed no evidence of tumors were kept for 60 days to evaluate the potential for tumor recurrence, at which time tumor characteristics, if any, were recorded. Table 13 contains the results of the experiments using mixtures of NDGA and ZnCl 2 as well as the results of experiments with NDGA alone or with ZnCl- alone. The effective doses (ED ) at different response levels (x), determined in micromoles for ZnCl, alone, NDGA alone, and for the combination of ZnCl- in different molar ratios with NDGA are provided in Table 13. The significant reduction in amount of either NDGA or zinc chloride required when given in combination is evident from the data. It is also seen that the total amount required for ED doses of the composition made up of NDGA plus zinc chloride is significantly less than the ED dose of NDGA or zinc chloride alone. TABLE 14 MICROMOLES ^50 ED 75 SS 90 E 95 NDGA 13.6 25.7 48.3 74.3 ZnCl 2 15.7 22.2 31.6 40.1 NDGA (l l) 1 5.7 8.8 13.6 18.2 +ZnCl 2 (1:2) 2 4.6 6.2 8.4 10.4 (1:2) 3 2.3 3.1 4.2 5.2 1 Calc ' d as micromoles NDGA or ZnCl 2 . 2 Calc ' d as micromoles ZnCl 2 3 Calc ' d as micromoles NDGA EXAMPLE 15 Experiments were carried out indicating that zinc acts to .stabilize the radical intermediate formed during oxidation of NDGA, thereby effectively stabilizing the NDGA and allowing it to exert its effect over a longer period of time before it is oxidatively inactivated. Aqueous ethanolic solutions of NDGA with and without various metal salts at pH 4, 7, and 10 were analyzed in an ESR spectrometer for the presence of free radical ion. The maximum peak height to minimum peak height of the ESR signal was measure over time. The reduction in ESR with time was used as a measure of free radical decay. The slope of free radical decay normalized to that of 3-hydroxytyrosine (DOPA) provided a measure of the relative rate constant of semiquinone free radical decay from NDGA. The various rate constants, K,, are given in Table 14. 8/ -74- EXAMPLE 16 To 36.7 grams of powdered Larrea divaricata were added 24.5 grams of powdered rosehips and the mixture was blended in a blender for 5 minutes. The blended mixture was then mixed with 100 milliliters of an aqueous solution containing 185.9 grams zinc chloride to form a paste. ' The paste was allowed to stand at room temperature for 24 hours. Thereafter, it was stirred and then placed in a screw-capped glass container. The container was placed in a humidified oven at 0 β C for 5 days. This incubated paste was then suspended in 500 milliliters of triple distilled water and shaken at room temperature for 24 hours on a reciprocating shaker. The zinc chloride extract solution was then evaporated to near dryness on a rotary evaporator at 90 β C under reduced pressure. A sufficient quantity of this dried zinc chloride extract was added to 120 grams of an ointment base consisting of 10% (w/w) stearyl alcohol and 90% (w/w) polyethylene glycol to obtain an ointment contain¬ ing 70% (w/w) of the extract. EXAMPLE 17 A sufficient quanitity of the paste of Example 17 was added to sterile deionized water to obtain a concentration of 10 grams per 100 milliliters of water. The aqueous mixture was thoroughly shaken for one hour on a reciprocating shaker, then the aqueous suspension was filtered through Whatman #1 filter paper in a Buchner funnel. The filtrate, an aqueous suspension, was used to irrigate wounds in the treatment of osteomyelitis. . EXAMPLE 18 Five selected human patients with osteomyelitis of duration of from several months to several years were treated topically with the solution of Example 17 and/or the paste of Example 1 ' 6. In all instances, the osteomy- elitis had been unresponsive to conventional treatment, and upon the application of the preparation, the patients received " no other conventional therapy except as indi¬ cated. In some cases, the wounds were debrided, prior to the application of the preparation. Upon application of the preparation, most patients experienced pain and a burning sensation over the area which had been treated and some patients additionally experienced swelling and inflamation. One patient'experienced severe nausea after an application of the preparation. Summaries, histories, and treatment are given below in Table 18. With respect to patient one, the disease process was so extensive that prior to treatment, a partial amputation of his foot was indicated. Kith respect to patient four,, the disease process was so extensive as to cause the exposure of the extensor tendons which normally necessitates their cutting. Moreover, as a result of the destruction of the bones of the ankle and foot, the possibility of an ankle fusion was considered; however, neither of these procedures was required as the patient became ambulatory without the assistance of either a cane or crutches within six months of the beginning of the treatment with the preparation. TABLE IB Time Required Previous Duration of Number of for Healing Patient DiaqonoβlB Culture Treatment Condition Treatments of Leβion 1 Chronic diabetic Hemolytic Antibiotics Several 2:13 days 1-1/2 months (62 year ulcer of left Staphylcoϋcus with no months apart old foot with osteo¬ aureus response male) myelitis extend¬ coagulaβe ing down to the positive metatarsal head capsule, involving 1 the flexor tendon • of the fourth toe 1 1 •» 2 Chronic ulcera- Staphvlcoccua Multiple Several 3:19 and 3 months (59 year tion of lateral aureus skin graft¬ yeara 23 dayβ old aspect of the coagulase ings! multi¬ apart * male) proximal fibula positive ple antibiotics . 3 ' Chronic osteo¬ Hemolytic Recent 35 years 4:over a 9-1/2 months (63 year myelitis of Staphylcoccuβ treatment 3-month for complete old left ankle and aureus with Beta- period recovery male) distal tibia coagulaβ dine soaks (first two positive with the solution and last two with TABLE I B (Cont ) Time Required Previous Duration of Number of for Healing Patient Diaqonoaiβ Culture Treatment Condi ion Treatments of Leβion 4 Ulcer of the left Hemolytic Antibiotics 7 months 2:5 days 1-1/2 months (70 year foot with necro¬ Staphylcoccus and soaks apart for leβloni old sis, drainage. aureus aftar 6 months female) destruction of the coagulaββ able to walk bones of the foot positive without and ankle Initiated crutches by a bite from a brown recluβe spider 1 5 Stasis ulcers of . Steroid unknown 2:9 days 2-1/2 months 1 (68 year lower left cream and apart. old extremity due ointment Treated with male) to circulatory a diuretic and Impairment soaks were applied to the area to reduce swelling apparently . caused by the treatment. EXAMPLS 19 Fifteen older dogs having perianal adenomas were treated topically with the ointment of Example 15 having a strength of 55% (w/w)• The normal treatment for such * condition is surgery; however, these older dogs were poor surgical risks. The tumor of each dog was biopsied and the ointment was applied topically into the biopsied incision. The duration of treatment varied depending upon the severity of the adenoma. Dogs with simple circumscribed adenomas required only one treatment. The dogs with more advanced adenomas generally required more than one treatment which were give . three to ive days apart. The treatment was successful in thirteen of the fifteen dogs. The treatment was not successful in ' two of the dogs which had extremely advanced cases of perianal adenomas. EXAMPLE 20. ' An incubated paste of rosehips, zinc chloride and Larrea divaricata prepared in accordance with the method of Example 16 was placed into gelatin capsules such that each capsule contained 200 mg of the paste. A patient with glioastrocytoma was treated orally with these capsules. • Prior to this treatment the patient had a resistant tumor which displaced the cranium and protruded from the right lateral aspect of the εkulli the pro¬ trusion measured 7 7 mm. The patient received 200 mg oral doses four times a day for a total daily dose of 800 mg. Observable and subjective improvement occurred within seven days; in 71 days the tumor had become cystic and lysed. The protuberance of the skull was reduced to near normal dimensions by repeated aspirations of the clear amber cystic tumor fluid. The patient has been maintained on the 200 mg capsules given four times daily EXAMPLE 21 Eleven cutaneous ulcers in eight human patients were treated with a formulation containing 5% zinc chloride and 4.6% NDGA w/w. If excessive necrotic material was present, debridement of non-viable and foreign material was performed either surgically or with wet-dry dressings prior to treatment. The test compound was applied directly to the cutaneous ulcer in an amount sufficient to cover the visual margins of the ulcer. The treated ulcer was then covered with a loose dressing and the patient advised against washing the treated area for a reasonable period of time. A scab or crust was observed to form on the surface of the ulcer. Normally within two weeks the crust had loosened to where it was sluffed off or could be readily removed.- It-was observed tha -granulation of the tissue in the ulcer had occurred in those ulcers which slowed clinical improvement. A second treatment with the Ccmpound was applied after removal of the crust. The patient was visually examined and the ulcer measured within two weeks after the initial treatment. There¬ after, the patient returned twice a month for two months for a visual examination and measurement of the ulcer. Of the eleven (11) treated lesions, seven (7) were clinically improved. EXAMPLE 22 Six (6) Kaposi's sarcomas in human patients were treated with Compound A, (a formulation containing 29.8% zinc chloride and 4.6% NDGA w/w) which was applied directly to the lesion with a thickness of approximately 2 mm and confined to the visual margins of the lesion. The lesion was then covered with a dressing and the patient advised against washing the treated area for a reasonable period of time. The patient was visually examined 1, 2, 3, 7 and 14 days after the initial treatment. If possible, accurate measurements of the lesion were. taken and recorded. A second application of Compound A was applied as deemed necessary. After 14 days, a biopsy was obtained if the lesion appeared clinically improved. If the biopsy continued to show evidence of Kaposi r s sarcoma or if the lesion was not clinically improved by the 14th day after the initial treatment, the patient was withdrawn from the study. Due to the serious nature of the disease, the 14-day time period was arbitrarily chosen as the termination point in order to provide patients who had not clinically improved the opportunity to pursue other methods of treatment regardless of biopsy results. EXAMPLE 23 Cultures of representative microorganisms which included Gram negative and Gram positive bacteria, yeasts and roolds were prepared to assess the e fect of composi¬ tion A of Example 10, as well as its separate components* on the survival and/or growth of the microorganisms. The microorgan sms and the culture media used are given below. o Streptococcus sp. , Group C, ATCC 9342 (Stp. Pyocenes, Lance ield Group A) • o Staphylococcus aureus (penicillin sensitive) , ATCC 5144 o Staphylococcus aureus (penicillin resistant) , ATCC 13301 ° Escerichia coli, ATCC 11229 o Proteus mirabilis, ATCC 4675 o Mycobacterium smegmatis, ATCC 20 ° Bacteroides fraσilis, ATCC 23745 o Candida albicans, ATCC 28366 ° Candida kruseri, ATCC 2159 O Trichophyton mentacrophytes, ATCC 9533 ° K crosporum canis, ATCC 9084 All of the bacterial species, including M. speor.atis, were found to grow well in tryptic soy broth with dextrose (TSB) . Good growth was also obtained with the yeast species in this medium. Although the fungal species grew in TSB, they grew somewhat better in Sabouruad's broth (SAB), and for the broth dilution tests with T. entagrophytes and M. canis Sabouruad's was used. For spore production the fungal species were grown on malt-soil extract agar. A series of tests were devised to determine the effect of direct, exposure of the microorganisms to the test compositions. The tests were conducted according to the following general procedure. Sterile tubes of a growth medium (broth) appropriate for the bacteria, yeas , ox mold -under -test were inocu¬ lated and allowed, to grow until the tube exhibited ' the maximum turbidity that could be expected or the particu¬ lar species. For most barte ia and yeasts this time was 24 hours. Tor molds the procedure was different in that the fungal species were inoculated onto the surface of a malt extract-soil extract agar slant and allowed to grow at room temperature until a heavy ycelial growth vita heavy spore production was observed. At this time the spores were washed from the mycelia with sterile water and agitation using a vortex mixer. The spore suspension was filtered through four layers of sterile cheesecloth into sterile tubes. The spore suspensions were handled from this point in .the same manner as broth suspensions of bacteria or yeasts. One milliliter of the bacter al, yeast, or mold spore suspension was transferred to a sterile 12-ml glass, conical, centrifuge tube covered with a sterile cap and centrifuged at 3,000 rp for 15 in. Ce tri- fugation was done at room temperature using a benchtop, angle-head, clinical centrifuge (Clay-Adams) • After the bacteria, yeast, or mold spores were pelleted, the supernatant fluid was decanted and the tubes inverted over paper saturated with a biocide placed in a bacteri¬ ological hood. The pellets in the centrifuge tubes were then mixed with 1 gram of the undiluted test material and allowed to remain in contact for 2 hours at 37*C for the bacteria and yeasts and at 25 β C for the mold spores. At the end of the contact time, the test mixture was diluted l ' to 10 with growth medium (TSB or SAB broth). Additional serial dilutions were made from the initial dilution up to 1 x 10 . Each material was tested in triplicate. The controls, which consisted of the icrobial cells incu¬ bated with 1 gram of mineral oil, were diluted in the same way. All dilutions of both test materials and controls were then incubated at an appropriate tem¬ perature of 37°C for bacteria and yeasts and 25*C for molds to allow for growth of any viable cells present * All bacterial species except M. smegmatis were incubated for 48 hours; M. smegmatis was incubated for 7 days. Yeast tests were incubated 48 hours. Molds were incubated for 10 days. For a determination of growth response, growth in tubes containing test compositions was compared to the growth in a mineral oil control at an equivalent dilution. Growth was indicated by turbidity in the broth medium. Results of the direct exposure tests are given in Table 23« Direct Bxpoaure Yeats (Organism Kxpoeβd to the Coapoaltion (or 2 Hours Prior to Dilution in feat Broth) Test Broth Dilution 10 -1 10 -2 10 -3 10 -4 10 -5 10 *C 10 -1 o -t 10 -s cø ptt f c Teat Broth , S.5 6,6 7.0 7,0 7.0 7,0 7 * 0 7.0 D3 Precipitation heavy heavy slight oC Teat Compoun ppt ppt ppfc „ PP* H G Growth in m Streptococcus Test Broth 0/3 0/1 0/3 0/3 0/3 0/3 0/3 0/3 pyoganeβ Growth in Mineral OH Control m Growth in fitaphylococcua Teut Broth 0/3 0/3 0/3 0/3 0/3 0/3 0/3 0/3 aureua (penicillin Growth in Mineral sensitive Oil Control Growth in Bacherichia Tetit Broth 0/3 0/3 0/3 0/3 0/3 0/3 0/3 0/3 coll Growth in Hineral Oil Control 1. No growth ahown in any of the three tubua at that dilution. 2. Indicatea growth of eella occurred. TABLE 23 Co t ) Test Broth Dilution »o-» - 2 - 1 ">".' l- 5 -i 10 • 10~' It "1 10"*I pU of Teβt Broth 5.5 7.0 7.0 7.0 7,0 7.0 - %A Precipitation heavy . heavy alight of Teat Ct pound ppt p t -EE£ f c c Growth in ra ω Hycobactarlu* Teβt Broth 0/3 0/3 0/3 aaegaa la Growth in Mineral Oil Control m Gro th in Bactβriodββ Test Broth 0/3 ■0/3 0/3 ω x fraglllβ Growth in Mineral rn m Oil Control Growth in Candida Test Broth 0/3 0/3 0/3 0/3 0/3 0/3 0/3 albicana Growth in Mineral Oil Conrol Growth in Mlcroaporun Teat Broth 0/3 0/3 0/3 0/3 canis Growth in Mineral Oil Conrol EXAMPLE24 Tests vere conducted on the' effect of the direct exposure of representative microorganisms to several separate components of the compositions of Example 10- Pego base alone was tested in one series of evaluations to deteirmine whether or not inhibition by this carrier would have to be considered in evaluating the results of the individual ingredients dissolved in it. In order to better approximate the effects of pego base in the Example lo ormulations, the amount of poly¬ ethylene glycol present in the formulation was calcu¬ lated. The pure base material was then diluted with water to this concentration. Mineral oil was used as a positive control. Nordihydroguaiaretic acid . (NDGA) and desmethyl DGA {DK-NDGA) diluted in pego base were also tested for in¬ hibitory properties against representative gram-negative and gram-positive bacteria and yeasts covering the spec¬ trum of microorganisms used-in these tests. The initial concentration of the compounds tested was equivalent to the amount present in the composition, and the general procedure outlined in Example 23 was followed. After a 2-hour exposure of the microorganisms to this initial concentration, progressive 1 to 10 serial dilutions of the mixture were made to assess viability of any microorganisms present. Results are shown in Table 24. EXAMP S " 25 A combination of EDTA (ethylenediaminetetraacetic acid) and ∑inc chloride in pego base at the concentration in which these components are present in composition A of Example 10 was tested for its effect on the viability of representative microorganisms. All organisms given in Example 23 ' were tested except Candida kruseri, ' and ■Kicrosporum canis. The test procedure* followed was that generally described in Example 23 *' . The initial test composition of EDTA/zinc to which the microorganisms were exposed for 2 hours of direct contact had a pH of about 2.0. None of the orcanisms tested retained viability after exposure to this test mixture. All mineral oil controls showed " abundant (4 ) growth. In every test a heavy precipitate formed when the test mixture was diluted to 10 . The pH of the 10 * dilution was 4.75. No precipitate formed at the 10 ** dilution (pH 1.8),- the 10~ 3 dilution (pH 6.60) or the ID "4 dilution <pH 7.0). EXAMPLE 26 A test was conducted to assess the growth of Escherichia coli and Staphylococcus aureus in broth containing composition A of Example 10 , NDGA or desmethyl NDGA diluted in glycerol. Test parameters and results are given below. * TABLE 49 Growth (48 hr at 37*C) E. coli S. aureus Glycerol 1 1 aall iin 10 al TSB «: 0.1 al in 10 al TSB NDGA in Glycerol 100 pptt (as NDGA) in TSB 3ι^* 1,000 ppa (as NDGA) in TSB 3* Desmethyl NDGA in Glycerol 100 ppm (as DK-NDGA) in TSB 3 0 1,000 ppjr. (as DK-NDGλ) in TSB 3 0 Compound A in Glycerol .4 * .4 100 ppa 4 ^ * " <<5.6 ppa NDGA + 1.1 ppa BHT) 1,000 ppn A 0 (46 ppa NDGA 411 ppa BHT) EXAMPLE .27 A series of broth dilution tests were conducted to assess the ef ect of composition A of Example 10" and its separate components on the growth of microorganisms. The individual test materials were incorporated into pego base at the concentration in which they are present n the composition for testing. EDTA and zinc chloride wex tested together. Each original formulation was diluted 1 to 10 with growth medium r •{usually tryptic soy broth with glucose) , and subsequent 1 to 10 dilutions were made of the previous dilution usually up to 1 x 10 * • This test was done with no consideration given to the solubility of the test material when diluted. Zn all cases, controls consisting of cells in mineral oil diluted in TSB were made to test the effect of the medium on growth. The pΞ determination of each series " of materials was made by testing a duplicate set of tubes that .were uninoculated. Each dilution tube containing 10 al. test broth was inoculated with 0.1 ml. of a 24-hour culture of all test ' species except M. smegmatis and the mold species. Spore suspensions of fungi (10 days) were used to inoculate the tubes for testing effects on M. canis and T. enta- grophytes, and Sabouraud's broth was used for dilution " because the fungal species grew somewhat better in this medium than in TSB. Zn general, a stationary phase culture of each test species was used. Hesuits of the broth dilution tests are given in Table 27 , The pH values given in the tables apply only to the dilution shown. The readings of turbidity in the growth media which indicate growth of the microorganism are rated from 0 « no growth, to 4+ * turbidity equal to the control. A 4+ reading for one microbial culture does not mean that the turbidity of that culture was the same as a 4+ reading -91- , * ,... f t . 4+ reading means that turbidity for any other culture. A *+ reaα i in the tubes , of a particular te t «« equal t turbidity of the appropriate control at the compared. 8 -92- TABLE 27 (Cont. Broth Dilution Teete Deeaathyl EDTA Teat Teat Coapound NDGA in Pego Baae NDGA In Pego-Baaa tine Chlor|de NlcroorαaniβB Broth Dilution 10 -1 10 -2 10 -3 10 -4 10 -1 10 -2 10 -3 10 -4 10 -1 * 1 -Λ 0- Ϊ 10 Λ -3 10 -4 Broth pH 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 1.β 4. 75 6.6 7.0 _4 4 Streptococcus pyogenea 2* 4 + 4* 0 4* 4* 0 0 0 4* 4 4 Staphylococcua aureua (Pen. Resistant) 0 4* 4* 0 2* 4 + 0 0 0 4* .4 4 'Staphylococcua pyoqenea (Pen. Senaitive) 0 4* 4* 0 1* 4* 0 * 4* 4* .4 4 Escherichia coll t 4* 4* 1* 4* 4* 0 0 * 4 + 4 Proteus mirabilia • 4 4* 4* 4* 4 + 4* 4* 0 0 4* 4* 4 Mycobacteriurn smeqmat1a 0 0 4* 4* 0 1* 4* 0 0 0 2* 0 .4 B cteriades fragillβ 0 2* 2* 0 0 1* 0 0 0 2* 4 Candida albicans 1* 2* 3* 4* 1* 2* 4* 0 0 4* 4* 4 Candida kruseri 0 0 4* 4* 0 2* 3* not tested Trichophyton mentagrophytea 0 0 2* 2* 0* 0* 2* 2* 0 0 2* 2* Nicrosporum caniβ 0 0 * 4* 0 0 2* 2* not <tested -94- EX.AMP S 28- Compositions containing NDGA, zinc chloride or A combination of NDGA-2n vere tested for antimicrobial activity individually against seven gram positive and gram negative bacterias, yeasts and molds. In a preliminary screening test, a vehicle contain¬ ing 30% polyethylene glycol-200 (PEGO-200) + 0.1% sodium ascorbate in deionized water at various concentrations was shown to exhibit no *inhibitory effect on microbial growth and vas chosen as the diluent for the test com¬ pounds. Stock solutions of the test compounds in 30% PEGO-200/water vere prepared at the following veight - percent concentrations: 4.6% NDGA + 0.1% ascorbic acidj 5.0% ZnCl, -*• 0.1% sodium ascorbate; and 4.6 NDGA + 5.0% 2nCl 2 4- 0,1% sodium ascorbate. Aliquots of the stock solutions vere diluted 1:10 and 1:100 with the 30% PEGO-200 diluent. The stock solutions vere further diluted IslO with Brain ϋeart Infusion Agar, vhich vas melted at 45 β C prior to the addition of the test solu¬ tions. The agar containing the test solutions vas then poured into 50 x 90 mm petri dishes and allowed to dry for four hours at room temperature prior to inoculation * All Brain Heart Infusion slants vere started at 35*C anaerobically except for T. mentacrophytes at 27*C and P. acnes at 35 β C anaerobically. Those microbial slants incubated at 35 % C were subsequently transferred to new slants at 35 β C and incubated at the same temperature. All slants were harvested with 1 ml saline containing 0.05% Tween-BO and diluted vith saline in the following amounts to be used as working inocula: 1 ml each of Σ. Coli, P. aeruginosa f S. aureus and B. subtilis vas diluted with 99 ml εalinej 1 ml of C. albicans and P. acnes was diluted vith 9 ml saline? 1 ml of T. mentagro- phytes was le t undiluted. One crop of working inocula vas added to the " petri dishes containing the test compounds and allowed to absorb into the agar. Uninoculated (control) and inocu¬ lated dishes were sealed and incubated in the dark for 5-7 days under the following conditions: P. acnes anaero¬ bically at 35*C, T. mentagrophytes at 27 β C and the remaining at 35*C aerobically. The plat *s vere visually' observed for microbial growth. Table 28A shows the dose levels and inhibitory effects of the test compounds. Table 28Σ, provides a summary of the results with the test compounds showing the lowest dosage with complete inhibi¬ tion. TABLE 3Q.A t tt t4 tt tt t 0,5% SnClj t+ tt t t 0.05% ZnCl 2 Q.005% ZnCl 2 t tt 1 tt tt tt t o > t* 44 0.46% NDGA 40.5% Z Cl j t t o 1 tt tt tt 0.046% MDGJ.40.05% ?nCl 2 tt — 0.0046% NDGA 40.005% nClj Vehicle Control (with 0.1% Sodlu* A β cprbata) 0.2% polyethylene Glycol-200 - 2.0% polyethylene Glycol-200 - 20.0% polyethylene Glycol-200 - R β eulte ere found In triplicate sasp ss ♦ + - complete Inhibition of growth + . artial Inhibition o»e growth) - Little or no inhibition (good growth! E AMPLE 29 A composition containing 5% NDGA plus 10% zinc chloride was tested for antiacne activity. Comedones were induced in both ears of rabbits by daily application of coal tar to the skin of the external ear canal. The right ear of each an.imal was treated with the test agent daily (5 days) for two weeks. The left ear served as the untreated control. Comedones in the test ears were small compared to those in the control ear. Horny material in the test ears was moderately reduced in 3 out of 5 animals. Peri-co edonal inflammation was significantly less in treated ears compared to test ears treated with vehicle alone. While there have been described what are presently believed to be preferred embodiments of the invention, it wi.ll.be apparent to a'person skilled in the art that numerous changes can be made in the ingredients, conditions and proportions set forth in the foregoing embodiments without departing from the invention as described herein and as defined in the appended claims.

Claims: yhat Is Claimed 1st 1. antitumor composition comprising the follow¬ ing components! (a) zinc chloride; and (b) nordihydroguaiaretic acid or a pharmaceutically acceptable salt thereof; said components being present in amounts effective to prevent the replication of tumor cells. 2. The composition of Claim 1 in which zinc chloride is present in an amount of between about 1.0 and about 30.0 veight percent and nordihydroguaiaretic acid is present in an amount of between about 2 and about 18 veight percent. 3. The composition of Claim 1 in vhich zinc chloride is present in an amount of about 30 veight percent, nordihydroguaiaretic is present in an amount of about 4.6 veight percent, and the composition also includes ethylenediaminetetraacetic acid in an amount of about 14.7 veight percent and BHT in an amount of about 1.1 veight percent. 4. Λ method for treating conditions selected from the group consisting of basal cell epithelioma, actinic keratosis, cutaneous ulcers, and sarcoma comprising topically administering to a patient in need of such treatment a composition as described in Claim 1. 5. A method of treating a tumor selected from the group consisting of mast cell tumors, squamous cell carcinomas, adenocarcino as, basal cell carcinomas, sarcoid tumors, and melanomas comprising topically, administering to a mammal in need of such treatment a composition as described in Claim 1. 6. A method for preventing the replication of cells in βolid human tumors selected from the group consisting of squamous cell carcinomas, breast adeno¬ carcinomas, renal eelir tumors, gliomas, melanomas, and colon tumors, comprising contacting said cells vith a composition as described in Cla.Ua 1. 7. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) a catecholic butane of the formula: vhere R. and R, are independently H; 1-12 alkyl; 1-12 alkenyl; 1-12 alkoxy; 1-12 alkenoxy; (C0) n (CH 2 ) m (C0 2 ) R . vhere n*0-l, m=l-4, p«0-l, and R_ is independently H,~ a a 1-12 alkyl, and 1-12 alkenyl; and glycoside moieties and R-substituted glycoside moieties vherein any of the hydroxyl hydrogens- thereof may be replaced by R, vith R being independently 1-2 alkyl, and 1-2 alkoxy; and taken together are methylene; R-, g and R g may be attached to any separate location C.-Cg of their benzene ring, and are indepen¬ dently H; 0; OR. (with R. defined as above); and when R- and R β or R g and R« are adjacent, taken together they may be methylene; R- and R, are independently H, CH-, C j H c , CHO and COOH; and R- and R, are independently H, OH, OCH- and 0; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 8. The composition of Claim 1 in which the cate¬ cholic butane is selected from the group consisting of • compounds corresponding to the formula: vhere R j -Kg are OR j 1 are define y- of R, and R 2 ; and pharmaceutically acceptable salts thereof. 9. The composition of Claim 7 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, trivalent iron, antimony, cadmium and vanadium; and (b) The catecholic butanes are selected from the " group consisting of 3,4,2' ,5'-quatrahydroxy-1,4-diphenyl¬ butane; 2* ,3* ,4' ,3,4-pentahydroxy, 1,4-diphenylbutane; 3',4' ,5*, 3,4-pentahydroxy, 1,4-diphenylbutane; and 1- (3 ,4-dihydroxyphenyl) , 4-phenylbutane; nordihydroguaia¬ retic acid (1,4-bis-(3,4-dihydroxyphenyl) butane); dihydroguaiaretic acid (1,4-bis-(3-methoxy,4-hydroxy- phenyl) , 2,3-dimethylbutane) ; nordihydroguaiaretic acid tetraacetate (1,4-bis(3,4-diacetoxyphenyl) ,2,3-dimeth l- butane; nordihydroguaiaretic acid propionate (1,4-biβ- (3,4-dipropyloxyphenyl) , 2,3-dimethylbutane) ; nordihydro¬ guaiaretic acid glycoside (l-(3-hydroxy, 4-glucaryl-O- phenyl) , -4-dihydroxyphenyl, 2,3-dime hyl-butane or 1-(4-hydroxy, 3-glucaryl-O-phenyl) , 4-dihydroxyphenyl, -. 2,3-dimethylbutane) ; nordihydroguaiaretic acid glycoside tetraacetate (1- (3-hydroxy, 4-tetraacetoxyglucaryl-O- phenyl) , -dihydroxyphenyl, 2,3-dimethylbutane or l-(4- hydroxy, 3-tetraacetoxyglucaryl-0-phenyl) , 4-dihydroxy- phenyl, 2,3-dimethylphenylbutane) ; nordihydroguaiaretic acid diphenoxyacetic acid diethyl ether (1,4-bis (3-di- hydroxy) 4-diethylcarbonylmethoxyρhenyl) , 2,3-dimethyl- butane or 1,4-bis (4-dihydroxy, 3-diethylcarbonylmethoxy¬ phenyl) , 2,.3-dimethylbutane) ; nordihydroguaiaretic acid triphenoxyacetic acid diethylether (l-(3-hydroxy, 4-ethyl- carbonyl ethoxyphenyl) , 4-(diethy1carbonyI ethoxyphenyl) β 2,3-dimethylbutane or l-(4-hydroxy, 3-ethylcarbonylmethoxy¬ phenyl) , 4-(diethylcarbonylmethoxyphenyl) , 2,3-dimethyl- butane) ; nordihydroguaiaretic acid tetraethylhemisuccinate (1,4-bis(tetraethylhemisuccinylphenyl) , 2,3-dimethyl- butane; nordihydroguaiaretic acid tetramethylether diol (1,4-bis (3,4-dimethoxyphenyl) 2,3-dimethyl, 1,4-dihydroxy- butane) ; nordihydroguaiaretic acid dimethylene ether dione (1,4-bis (3,4-dimethylenedioxyphenyl) 2,3-dimethyl, 1,4-dioxobutane) ; nordihydroguaiaretic acid tetramethyl¬ ether dione (1,4-bis (3,4-dimethoxyphenyl) , 2,3-dimethyl, 1,4-oκobutane) ; desmethyl nordihydroguaiaretic acid (1,4-bis (3,4-dihydroxyphenyl) butane); desmethyl nordi¬ hydroguaiaretic acid tetramethyl ether (1,4-bis (3,4- di ethoxyphenyl) butane; .desmethyl dihydroguaiaretic acid; desmethyl nordihydroguaiaretic acid tetraacetate; desmethyl nordihydroguaiaretic acid propionate; desmethyl nordihydroguaiaretic acid glycoside; desmethyl nordihydro¬ guaiaretic acid glycoside tetraacetate; desmethyl nordi¬ hydroguaiaretic acid diphenoxyacetic acid diethyl ether; desmethyl nordihydroguaiaretic acid triphenoxyacetic acid diethylether; desmethyl nordihydroguaiaretic acid tetra¬ ethylhemisuccinate; desmethyl nordihydroguaiaretic acid tetramethylether diol; desmethyl nordihydroguaiaretic acid dimethylene ether dione; desmethyl nordihydroguaia¬ retic acid tetramethylether dione; and pharmaceutically • acceptable salts thereof. 10. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors comprising contacting said cells vith a composition according to Claim 9 in a pharmaceutically effective amount. 11. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of. zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) an optically active catecholic butane selected from compounds of where R, and R 2 are independently H; 1-12 alkyl; 1-12 alkenyl; 1-12. alkoxy; 1-12 alkenoxy; (CO) n (CH 2 ) ffi (C0 2 ) p R . vhere n β 0-l, m=l-4, p=0-l, and R, is independently H, 1-12 alkyl, and 1-12 alkenyl; and glycoside moieties and R-substituted glycoside moieties vherein any of the hydroxyl hydrogens thereof may be replaced by R, vith R being independently 1-2 alkyl, and 1-2 alkoxy; and taken together are methylene; R_, R β and R- may be attached to any separate location C.-Cg of their benzene ring, and are indepen¬ dently H; O; OR, (vith R. defined as above) ; and vhen R- and Rg or R g and R g are adjacent, taken together they may be methylene; R, and R. are independently CH., C-H-, CHO and COOH; and r R- and R, are independently H, OH, OCH, and O; its antipodes and racemic mixtures thereof; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 12. The composition of Claim 11 in vhich: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the optically active catecholic butane is selected from the group consisting of d,l NDGA; d,l-di- hydroguaiaretic acid; d,l-nordihydroguaiaretic acid tetraacetate, d,l-nordihydroguaiaretic acid propionate; d,l-nordihydroguaiaretic acid glycoside; d,1-nordihydro- guaiaretic acid glycoside tetraacetate; d,l-nordihydro- guaiaretic acid diphenoxyacetic acid diethyl ether; d,l-nor ihydroguaiaretic acid trihenoxyacetic acid diethylether; d,l-nordihydroguaiaretic acid tetraethyl¬ hemisuccinate; d,l-nordihydroguaiaretic acid tetramethyl¬ ether diol; d,l-nordihydroguaiaretic acid dimethylene ether dione; d,l-nordihydroguaiaretic acid tetramethyl¬ ether dione; and pharmaceutically acceptable salts thereof. 13. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells vith a composition according to Claim 12 in a pharmaceutically effective amount. 14. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) a tetralin selected from compounds corresponding to the formula: where R, and R 2 are independently H; 1-12 alkyl; 1-12 alkenyl; 1-12 alkoxy; 1-12 alkenoxy; (C0) n CH 2 ) m (C0 2 ) R & t vhere n=0-l, m=l-4, p*0-l, and RA is independently H, 1-12 alkyl, and 1-12 alkenyl; and glycoside moieties and R-substituted glycoside moieties vherein any of the hydroxyl hydrogens thereof may be replaced by R, vith R being independently 1-2 alkyl, and 1-2 alkoxy; and taken together are methylene; R-, Rg and R g may be attached to any separate location C.-C, of their benzene ring, and are indepen¬ dently H; O; OR, (with R, defined as above); and when R- and Rg or R g and R- are adjacent, taken together they may be methylene; ~" « and R. are independently CH-, C 2 H-, CHO and COOH; g is H, OH, OCH, and 0; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. - s- 15. The composition, of Claim 11 in vhichi (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, txi— ' valent iron, antimony, cadmium and vanadium; and (b) norisoguaiacin; and. pharmaceutically acceptable salts thereof. 16. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells with & composition according to Claim 14 in a pharmaceutically effective amount. 17. .An antitumor composition comprising the follow¬ ing components: (a) metal salt selected from the group consisting of salts of zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) catecholic butenes selected from compounds corresponding to the formula: where R j and R 2 are independently H; 1-12 alkyl; 1-12 alkenyl; 1-12 alkoxy; 1-12 alkenoxy; (C0) n (CH 2 a (CO j ) Ra. vhere n«0-l, m=l-4, p=0-l, and Ra_ is independently B, 1-12 alkyl, and 1-12 alkenyl; and glycoside moieties and R-substituted glycoside moieties wherein any of the hydroxyl hydrogens thereof may be replaced by R, vith R being independently 1-2 alkyl, and 1-2 alkoxy; and taken together are methylene; R-, Rg and R Q may be attached to any separate location C.-Cg of their benzene ring, and are indepen¬ dently H; O; OR, (with R, defined as above) ; and when -y and Rg or Rg and R Q are adjacent, taken together they may be methylene; R« and R, are independently H, CH-, C 2 H-, CHO and COOH; and Re and Rg are independently H, OH, OCH * and O; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 18. The composition of Claim 17 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, trivalent iron, antimony, cadmium and vanadium; and (b) the catecholic butene is selected from the group consisting of: l,4-bis-(3,4-diroethylenedioxyphenyl) 1,3-butene and 2,3-biε (3,4-dimethoxybenzylidene) succinic acid " ; l-(3,4-diacetoxyphenyl)-4-phenyl-buta-l,3-diene; and l-(3,4-dihydroxyphenyl)-4-phenylbutadiene; and pharmaceutically acceptable salts thereof. 19. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells vith a composition according to Claim 18 in a pharmaceutically effective amount. 20. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of- zinc, trivalent chromium, yttrium, divalent ' . and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) an azine selected from compounds corresponding to the formula: where R, , R 2 , R, * and R 2 * are independently H; 1-12 alkyl; 1-12 alkenyl; 1-12 alkoxy; 1-12 alkenoxy; (CO) n (CH -, * )_JΩ (CO * ,)p RA. vhere n»0-l, m=l-4, p«0-l, and RA is independently H, ' l-12 alkyl, and 1-12 alkenyl; and glycoside moieties and R-εubstituted glycoside moieties vherein any of the hydroxyl hydrogens thereof may be replaced by R, vith R being independently 1-2 alkyl, and 1-2 alkoxy; and taken together are methylene; and R and R ' are defined as R, and R, 1 respec- tively, and vhen R 'O and R 2 *0 are adjacent they may be, taken together, methylene; and pharmaceutically acceptable salts thereof; said components being present in amounts effective"to prevent the replication of tumor cells. 21. The composition of Claim 20 in vhich: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- an divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the azine is selected from the group consisting of vanillin azine and syringaldazine; and pharmaceutically acceptable salts thereof. 22. A. ethod for preventing the replication of human breast adenocarcinoma cells in solid tumors comprising contacting said cells vith a composition according to Claim 21 in a pharmaceutically effective amount. 23. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of zinc, trivalent chromium, yttrium, divalent' and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) para-substituted benzenes selected from com¬ pounds corresponding to the following formulas vhere R, * 2 , R, • and R 2 ' are independently H; 1-12 alkyl; 1-12 alkenyl; 1-12 alkoxy; 1-12 alkenoxy; (C0) n (CH,) (CO,1 R . vhere n«0-l, m«l-4, p«0-l, and β is * m *• p a a independently H, 1-12 alkyl, and 1-12 alkenyl; and glycoside moieties and R-εubst ' ituted glycoside moieties wherein any of the hydroxyl hydrogens thereof may be replaced by R, with R being independently 1-2 alkyl, and 1-2 alkoxy; and taken together are methylene, and there may be double bonds independently at 1-2 and l'-2 f of the chains; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 24. The composition of Claim 23 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the para-substituted benzene compounds are selected from the group consisting of l,4-biε-(3,4-di- hydroxyphenethyl) benzene; 1,4-bis-(3,4-dimethoxy- phenethyl) benzene; 1,4-bis-(3,4-dihydroxystyryl) benzene; and 1,4-bis-(3,4-dimethoxyεtyryl) benzene; and pharma¬ ceutically acceptable salts thereof. 25. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells with a composition according to Claim 24 in a pharmaceutically effective amount. 26. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) a bridged dicatecholic compound wherein the bridge is a 3-, 5- or 6-member carbon chain, and the catecholic hydroxy1 hydrogens may be replaced with radicals which are, independently, 1-12 alkyl; 1-12 alkenyl; 1-12 alkoxy; 1-12 alkenoxy; (CO) (CHO (C0 2 ) R , vhere n=0-l, m=l-4, ρ*0-l, and R_ is independently H, 1-12 alkyl, and 1-12 alkenyl; and glucoside moieties and R-substituted glycoside moieties vherein any of the hydroxyl hydrogens thereof may be replaced by R, with R being independently 1-2 alkenyl and 1-12 alkoxy; and taken together are methylene; and vherein the bridging chain may bear 1-5 alkyl substituents; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 27. The method of ClaiΛ 26 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the bridged dicatecholic compound is 1,6- bis(3,4-dihydroxyphenol) butane; and pharmaceutically salrts thereof. 28. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells with a composition according to Claim 28 in a pharmaceutically effective amount. 29. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of. zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) phenolic acids and acidic anhydrides selected from the group consisting of compounds corresponding to the following formula: wherein n ~R are independently H, OH, 1-12 alkyl, 1-12 alkenyl, 1-12 alkoxy, 1-12 alkenyoxy, 1-12 alkylcarboxy, 1-12 alkenylcarboxy, or, taken together, are methylene dioxy; n « 0-1 3 « 1-5 alkyl, 1-5 alkenyl, hydroxyrl-5-alkyl, hydroxy-l-5-alkenyl; oxy-l-5-alkyl; oxy-1-5 alkenyl, or oxo-l-5-alkyl, oxo-1-5 alkenyl; and 4 is an acid moiety, a 1-5 alkyl ester moiety, a 3-6 carbon dicarboxylic acid moiety, or a 3-6 carbon dicarboxylic acid anhydride moiety. 30. The composition of Claim 29 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the phenolic acid or acid anhydride is selected . from the group consisting of 3,4-dihydroxybenzoic acid; ethyl 3,4-dihydroxybenzoate; cinnamic acid; mandelic acid; p-hydroxycinnamic acid; 3,4-dihγdroxycinnamic acid; 3,4-dihydroxyphenylacetic acid; 4-hydroxy, 3-methoxy- cinnamic acid; 2-(3,4-dimethoxybenzylidene) succinic acid; and 2-(3,4-dimethoxybenzylidene) succinic anhydride; and pharmaceutically acceptable salts thereof. 31. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells vith a composition according to Claim 30 in a pharmaceutically effective amount. 32. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of- zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) a substituted catecholic compound selected from compounds corresponding to the following formula: wherein R, and R 2 are independently, 1-12 alkyl, 1-12 alkenyl, or taken together are methylene; and R, is 1-12 alkyl, 1-12 alkenyl, formyl, hydroxy-1- 12-alkyl, hydroxy-l-12-alkenyl, oxo-l-12-alkyl, or oxo-l-12-alkenyl; and pharmaceutically acceptable salts thereof; said components being present in amounts effect to prevent the replication of tumor cells. 33. The composition of Claim 32 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the substituted catecholic compound selected from the group consisting of 4-methyl catechol; 4-tert- butyl catechol; 3,4-dimethoxyρhenyl ethanol; 3,4-di- hydroxybenzaldehyde; vanillin; 3,4-dimethoxyacetophenone; and 3,4-methylenedioxypropiophenone; and pharmaceutically acceptable salts thereof. 34. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells with a composition according to Claim 33 in a pharmaceutically effective amount. 35. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) phenolic compounds selected from compounds corresponding to the following formula: wherein ^ is R or CH^ and R 2 and R, are independently H and 1-12 alkyl; and . pharmaceutically acceptable salts thereof; said components being present in amounts effect to prevent the replication of tumor cells. 36. The composition of Claim 35 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the phenolic co poundε are selected from the group consisting of phenol; 2-tertbutylphenol; 3-tertbutyl- phenol; 4-tertbutylphenol; thymol; and 2,3-dimethyl- phenol; and pharmaceutically acceptable salts thereof. 37. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells with a composition according to Claim 36 in a pharmaceutically effective amount. 38. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting - of salts of-zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, ono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) a substituted resorcinol selected from the group consisting of compounds corresponding the following formula: vherein R, and R 2 are independently H or CH»; and R, is 1-12 alkyl; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 39. The composition of Claim 38 in vhich: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b> the substituted resorcinols are selected from the group consisting of orcinol; 4-ethyl resorcinol; and olivetol; and pharmaceutical acceptable salts thereof. 40. A method for preventing the replication-of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells vith a composition according to Claim 39 in a pharmaceutically effective amount. " 41. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) a quinone selected from compounds corresponding to the following formula: wherein R, and R- are independently H and CH-; and vherein R, and R. are independently H and OH; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 42. The composition of Claim 42 in vhich: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the quinone compound is selected from the group consisting of hydroquinone and 2,5-dihydroxy-p-benzo- quinone; and pharmaceutically acceptable salts thereof. 43. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells vith a composition according to Claim 42 in a pharmaceutically effective amount. 44. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting of salts of " zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) a naphthalenic compound selected from compounds corresponding to the following formula: wherein n is 0-1; R, and R, are independently OΞ, CHO, and COOH; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of. tumor cells. 45. The composition of Claim 44 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the naphthalenic compound is selected from the group consisting of 2,3-dihydroxynaphthalene; 1-naphthalde- hyde; and 2-naphthaldehyde; and pharmaceutically accept¬ able salts thereof. 46. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells with a composition according to Claim 45 in a pharmaceutically effective amount. 47. An antitumor composition comprising the follow¬ ing components: (a) metal salt selected from the group consisting of salts of zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) a flavone, flavanone, coumarin, quinizarin, ellegic acid, or purpurogallin bearing 0-2 substitutents per ring, said subεtituentε being independently 1-12 alkyl, hydroxyl, 1-12 alkoxy, formyl, carboxy1 and oxosubstituents; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 48. The composition of Claim 47 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the organic compounds are selected fro the group consisting of flavone; flavanone; quercetin; 4-methyl esculetin; quinizarin; ellegic acid and purpuro¬ gallin trimethyl ether; flavanol (3-hydroxyflavone); (3,5,7-trihydroxyflavone) ; (3,3'4*-trihydroxyflavone); " (3,4* ,5-trihydroxyflavone) ; datiscetin (2' ,3,5,7-tetra- hydroxyflavone) ; fisetin (3,3*,4',7 tetrahydroxyflavone); (3,3' ,4'-trimethoxy-7-hydrox flavone) ; (3,3',4' ,7-tetra- methoxyflavone) ; orin 2',3,4',5,7-pentahydroxyflavone); (8-hydroxykaempferol) kaempferol (3,4 ♦ ,5,7-tetrahydroxy- flavone); quercetin (3,3' ,4*,5,7-pentahydroxy-flavone) ; quercetagetin (3,3' ,4* ,5,6,7-hexahydrox flavone) ; querce¬ tin 3,3'-dimethylether; quercetin-7,3'-dimethylether; quercetin 3'-methylether; kaempferol (3,4 » ,5,7-tetra- hydroxyflavone) ; kaempferol-3,7-dimethylether; kaempferol 3-methylether; kaempferol 7-methylether; kaempferol 3,4'-dimethylether; quercetin 3, ,3',4'-tetramethylether; quercetin 3,7,3*-trim thylether; quercetin 7,3',4 1 -tri¬ methylether; quercetin 3, -dimethylether; luteolin 7,3'-dimethylether <3»,4*,5, -tetrahydroxyflavone)» luteolin 3*-methylether; apigenin 7-methylether (4*,5,7- trihydroxyflavone) ; rutin (quercetin-3 rutinoside) 3,3' *,5,7-pentahydroxyflavone-3-rutinoside; chrysin (chrysoeriol 6,8-9-C-glucoεide) 5,7-dihydroxyflavone; isoquercetin 3,3*,4*,5,7-pentahydroxyflavone-3-glucoside; kaempferol 3-O-rhamnosylglucoside (3,4*,5,7-tetrahydroxy- • flavone); rhajnnetin-3-o-rhamnosylglucoside (3,3', *,5- tetrahydroxy-7-methoxyflavone); myricetin (3,3*,4*,5,5*7- hexahydroxyflavone) (dihydromyricetin 3*,5-dimethylether); hesperetin (herbacetin) 3,7-dimethylether; (3*,5,7-tri- hydroxy-4*-methoxy lavanone) ; quercimeritrin C 2 ,H 20 O, 2 3,3* ,4* ,5,7-ρentahydroxyflavone-7-D-glucoside [gossypitrin C 21 H 20°13 3>7,3'-trimethylether; catechin (3,3*,4*,5,7- flavanpentol) ; gallocatechin; polydine; adzelechin, eupatilin and 4*-demethyl-euρatilin; delphinidin (3,3',- 4* ,5,5*,7-hexahydroxyflavilium) ; leuteoliniden; cyaniden (3,3* ,4,5,7-pentahydroxy flavylium) ; peonidum (3,4*,5,7- tetrahydroxy-3*-methoxyflav lium) ; myrillidin; and enidin; and pharmaceutically acceptable salts thereof. 49. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells with a composition according to Claim 48 in a pharmaceutically effective amount. 50. An antitumor composition comprising the follow¬ ing components: (a) a metal salt selected from the group consisting . of saltε o zinc, trivalent chromium, yttrium, divalent and trivalent cobalt, nickel, magnesium, aluminum, mono- and divalent copper, trivalent iron, cadmium, antimony, mercury, rubidium, vanadium and other rare earth metals; and (b) an aliphatic acid, alcohol or aldehyde selected from the group conεiεting of dicarboxylic acids having four to twelve carbon atoms; and alcohols and aldehydes having four to twelve carbon atoms; and pharmaceutically acceptable salts thereof; said components being present in amounts effective to prevent the replication of tumor cells. 51. The composition of Claim 50 in which: (a) the metal salts are selected from the group consisting of nitrates, sulfates, acetates and halides of zinc, mono- and divalent copper, divalent cobalt, tri¬ valent iron, antimony, cadmium and vanadium; and (b) the aliphatic acids, aldehydes and alcohols are selected from the group consisting of adipic acid, azelaic acid, lauric acid, oxydiacetic acid, lauryl alcohol and octyl aldehyde; and pharmaceutically accept¬ able εaltε thereof. 52. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells vith a composition according to Claim 51 in a pharmaceutically effective amount. . 53. An antitumor composition comprising nordihydro- • guaiaretic acid in an amount of between about 16 and about 18 weight percent; and pharmaceutically acceptable salts thereof; in a suitable pharmaceutical carrier * 54. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors comprising contacting said cells with a composition according to Claim 53. in a pharmaceutically effective amount. 55. An antitumor composition comprising an organic compound selected from the group including 3-tertbutyl- phenol; 4-tertbutylphenol; p-hydroxycinnamic acid; norisoguaiacin; d,l- DGA; l-(3,4-diacetoxyphenyl)-4- phenylbuta-l,3-diene; and 1,4-bis-(3,4-dihydroxyphenethyl) benzene; alpha,omega-C j -C,^ dicarboxylic acids; and pharmaceutically acceptable salts thereof; in a suitable pharmaceutical carrier. ' 56. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors comprising contacting said cells with a composition according to Claim 55 in a pharmaceutically effective._. amount. 57. An antitumor composition comprising: (a) an organic composition or a pharmaceutically acceptable salt thereof in at least a potentially pharma¬ ceutically effective amount; (b) a zinc salt selected from the group consisting of zinc nitrates, sulfates, acetates, and halides in an amount sufficient to potentiate the activity of the organic composition. 58. The composition of Claim 57 in which: (a) the organic composition is selected from the group consiεting of nordihydroguaiaretic acid; 3-tert- butylphenol; 4-tertbutylphenol; p-hydroxycinnamic acid; norisoguaiacin; d,l-nordihydroguaiaretic acid; azelaic acid; l-(3,4-diacetoxyphenyl)-4-phenylbuta-l,3-diene; VP-16; VM-26; 4'-demethylepipodophyllotoxin; diethyl- εtilbestrol; dithranol; mitomycin; daunomycin; platinum cis-diaminedichloride; allopurinol; and (b) the zinc salt is zinc chloride. 59. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors compris¬ ing contacting said cells with a composition according to Claim 58 in a pharmaceutically effective amount. 60. An antitumor composition comprising: (a) zinc chloride? and (b) an organic compound selected from the group consisting of : phenol; hydroquinone; 3 ,4-dihydroxy- cinnamic acid; cinnamic acid; 4-hydroxy-3-methoxy cinnamic acid; 4-tertbutyl catechol; 3,4-dihydroxy benzaldehyde; 4-methyl catechol; 4-ethyl resorcinol; desmethyl-H-tetra- ethyl ether; quinizarin; olivetol; 2-tertbutylphenol; 3-tertbutylphenol; 4-tertbuty phenol; 2,3-dimethylphenol; thymol; 5-nitrovanillin; o-anisidine; purpurogallin trimethyl ether; vanillin; p-hydroxy-cinnamic acid; dihy roxynaphthalene; 2 ,5-dihydroxy-p-benzoquinone; • orcinol; pentafluorophenol; picric acid; 3- (3 ,4-dimethoxy- phenyl) propylamine-N, N-acid . HC1; 3 ,4-dimethoxyphenyl- ethanol; 3 ,4 -dimethoxyacetophenone; 3- (3 , 4-dimethoxy- phenyl) propylamine; 2 ,3-dihydroxybenzoic acid; 3,4-di- hydroxyhydro- cinnamic acid; 3,4-dihydroxyphenylacetic acid; 3 , 4-dih droxybenzoic acid; 2 ,3-dihydroxybenzalde- hyde 3 ,4-methylenedioxyproρiophenone; dl-NDGA; DGA tetraacetate; 1,4-bis (3, 4 -dimethyleneoxyphehyl) butene; vanillin azine; syringaldazine; 2 ,3-bis (3 ,4-d.imethoxy- benzoyl) butane; dihydroguaiaretic acid; norisoguaiacin; 2 ' ,3 * ,4 ' ,3 , 4-pentahydroxy-l,4-diphenylbutane; 3 * ,4' ,5' ,3 ,4- pentahydroxy-l ,4-diphenylbutane; l- (3 , 4-dihydroxyρhenyl) ,4- (2 , 5 -dihydroxyphenyl) butane; 1- (3 , 4-dihydroxyphenyl) -4- phenylbutane; calcein blue; quercetin; ellegic -acid; 4-methylesculetin; flavanone; flavone; lauric acid; adipic acid; azelaic acid; oxydiacetic acid; 1-naphthalde- hyde; 2-naphthaldehyde; epipodophyllotoxin; epipodophyllo¬ toxin glycoside; VP-16 ; VM-26; lauryl alcohol; chloranil; n-pctyl cyanide; octyl aldehyde; NDGA propionate; 3 ,4-di- hydroxybenzyla ine-HBr; 2-aminoρhenol; 1 ,6-bis- (3, 4 -di¬ hydroxyphenyl) hexane; andelic acid; 3-propyl catechol; l-4-bis (dihydroxy, diethylcarbony lmethoxyphenyl) , 2,3-di- eth lbutane; l- (3 ,5-dinitroρhenyl) -4- (3,4-dimethoxy- phenyl) butene-l; 1,4-bis (3 , 4-dimethoxystyrl)benzene; 1, -bis(3,4-dihydroxyphenethy1)benzene; beta-beta-bis(3,4- dihydroxyphenyl)-l,4-divinyl benzene; nordihydroguaiaretic acid diphenoxy acetic acid diethyl ester; nordihydroguai- * aretic acid diphenoxy acetic acid triethyl ester; l-(3,4- . diacetoxyphenyl)-4-phenylbuta-l,3-diene; nordihydroguai¬ aretic acid tetraethyl he isuccinate; nordihydroguai¬ aretic acid ςlucoside tetraacetate; nordihydroguaiaretic acid glucoside; l-(3,4-dihydroxyρhenyl)-4-phenylbuta- diene; 2,3-biε(3,4-dimethoxybenzylidene)-succinic acid; 1-(3,5-ditrifluoromethylphenyl)-4-(3,4-dimethoxyphenyl)- butene-1; 1-(3,4-dihydroxyphenyl)-4-(3,5-ditrifluoro¬ methylphenyl)butane; ethyl 3,4-dihydroxybenzoate; 2-(3, - dimethoxybenzylidene) succinic acid; 2-(3,4-dimethoxy- benzylidene)succinic anhydride; methyl carbamate nordi¬ hydroguaiaretic acid; ortho-para-desmethyl nordihydro¬ guaiaretic acid; NrSA-tetrapropionate; acetoxyphenyl butadiene; NDGA-tetraacetate; 1-(3,4-dihydroxyphenyl)-4- phenylbutane; l,4-biε-(3,4-dimethoxyphenyl)buta-l,4-diol; and pharmaceutically acceptable salts thereof; εaid components being preεent in amountε effective to prevent the replication of tumor cells 61. A method for preventing the replication of human breast adenocarcinoma cells in solid tumors comprising contacting said cells with a composition according to Claim 60 in a pharmaceutically effective amount. 61. A composition comprising at least 1 catecholic butane of the formula: wherein R, and 2 are independently H, lower alkyl, or lower. " acyl; independently H or lower alkyl; R-, g and R- are independently H, hydroxy, lower alkoxy or lower acyloxy; and ionic zinc.

Inventors: ALLEN LARRY M, JORDAN RUSSELL T, ALLEN, LARRY, M., JORDAN, RUSSELL, T.
Applicants: CHEMEX PHARMACEUTICALS INC, CHEMEX PHARMACEUTICALS, INC.
Application year: 1986
Main classification: A61K33
IPC codes: A61K31, A61K33, A61P35, C07C39