ANTIMICROBIAL LIPIDS

Abstract: The invention relates to compositions of skin-derived lipids that inhibit the ability of microorganisms to adhere to skin, inhibit the reproduction of microorganism and are toxic to microorganisms. The invention icludes the two fatty acids shown below and the derivatives or analogs thereof as shown in the figure.

Description: ANTIM ICROBIAL LIPIDS The present invention relates to compositions of certain antimicrobial skin pids and to methods of preparing and using these pids The invention also relates to non irritating compositions comprising these anti microbial skin pids The skin functions as a barrier between the outside world and the internal organs of the body It serves the protective function of keeping harmful microbial organisms from colonizing the interior of an animal Part of this protective function can be ascribed to the hpids present in epidermis, sebaceous secretions, or otherwise present at the skin surface The distribution of lipid types at the skin differs markedly from the distribution found in internal organs See, Nicolaides, Science, 1 86 1 9-26 ( 1 974) Some of these skin-derived hpids have been reported to have pharmaceutical activity in inhibiting the growth of microbial organisms See, Kabera et al , Antimicrobial Agents and Chemotherapy, 2 23-28 ( 1 972), However, many of the fatty acids among these antimicrobial lipids are known to be extremely irritating Non-irritating natural lipid compositions that prevent infection or biological decay are desirable, since they are unlikely to cause adverse reactions Therefore, what is needed in the art are such compositions formulated with non irritating lipids or such compositions wherein the antimicrobial action of the lipids is accentuated so that the lipids can be present at concentrations less than the threshold concentration for irritation Summary of the Invention The invention is described below with reference to the following formula H H I I (5) CH 3 (CH 2 ) a -C = C-(CH 2 ) b _ R 5 wherein a + b equals from 11 to 14 and b is an integer from 1 to 14, wherein R 5 is (a) CH 2 NR 1 R 22 , wherein R 21 and R 22 are independently hydrogen or C1 to C6 hydrocarbon, preferably C1 to C4 hydrocarbon, (b) C(0)-R 23 , R 23 is (i) NR 2 R 25 , wherein R 24 and R 25 are independently hydrogen or C1 to C6 hydrocarbon, preferably CI to C4 hydrocarbon, (n) OR 26 , wherein R 26 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (in) a hydroxyl, or (c) CH 2 OH The invention is further described with reference to the following formulas of preferred compounds Ϊ V (1) CH 3 (CH 2 ) 8 -C = C-(CH 2 ) 4 — R 1 H H (2) CH 3 (CH 2 ) 8 -C=C-(CH 2 ) 6 — R 2 ; H H I i (3) CH 3 (CH 2 ) 5 -C = C-(CH 2 ) 7 — R 3 - (4) CH 3 (CH 2 ) 3 -C V = C V-(CH 2 ) n — R 4 wherein n is an integer from 3 to 6 and R 1 , R 2 , R 3 and R 4 ^re independently (a) CH 2 NR 11 R 12 , wherein R 11 and R 12 are independently hydrogen or C1 to C6 hydrocarbon, preferably C1 to C4 hydrocarbon, (b) C(0)-R 13 , wherein R 13 is (i) NR 14 R 15 , wherein R 14 and R 15 are independently hydrogen or C1 to C6 hydrocarbon, preferably C1 to C4 hydrocarbon, (n) OR 16 , wherein R 16 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (in) a hydroxyl, or (c) CH 2 OH The hydrocarbon moieties referred to herein are preferably alkyl The formulas below describing fatty acid compounds are helpful to understanding the invention H H o i i II (1 a) CH 3 (CH 2 ) 8 - C = C - (CH 2 ) 4 _C -OH [C16 1Δ6] H H o 1 ' II (2a) CH 3 (CH 2 ) 3 - C = C — (CH 2 ) 6 -C -OH [C18 1ΔS] H H o 1 ' II (3a) CH 3 (CH 2 )5 -C =C-(CH 2 ) 7 _ c -oH [C16 1Δ9] [Palmitoleic] (4a) CH 3 (CH 2 ) s - ΪC = V C-(CH 2 ) n _ 1c-OH The above formulas refer to the cis configuration of the carbon-carbon double bond C 1 6 1 Δ6 and C 1 8 1 Δ8 are believed to be derived from sebum, i e , the secretions from sebaceous glands All of fatty acids ( 1 a)-(4a) described above have antimicrobial activity, particularly against a broad spectrum of gram positive bacteria, but also against other microorganisms including a number of gram negative bacteria They further inhibit the adherence of bacteria and fungi to animal skin Additionally, they are believed to be active against pid-coated viral particles C 1 6 1 Δ6 and C 1 6 1 Δ9 were surprisingly found to be non irri g ating, even at concentrations as high a 1 0% w/v These results were for example obtained by contacting skin with the fatty acid in a hydroxypropyl methylcellulose gel and in the presence of alcohol as high as 75 % Surprisingly, compounds of the formulas ( 1 ) - (5) have been shown to been found to have much greater antimicrobial activity when combined with an alcohol or a polyalkylene glycol In a first embodiment, the invention provides an antimicrobial composition comprising (A) antimicrobial activity enhancing effective amount of a component selected from the group consisting of (C2-C7) alkyl alcohols, polyf alkylene oxιde)s wherein the alkylene moieties are C2 to C4, and mixtures thereo f, and (B) a compound as follows (5) CH 3 (CH 2 ) a -C V = C V-(CH 2 ) b _ R»- wherein a + b equals from 11 to 14 and b is an integer from 1 to 14, wherein R 5 is (a) CH 2 NR 21 R 22 , wherein R 21 and R 22 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(0)-R 23 , R 23 is (i) NR 2 R 25 , wherein R 24 and R 25 are independently hydrogen or C1 to C6 hydrocarbon, (ii) OR 26 , wherein R 26 is glyceryl or a glyceryl fatty acid .ester, wherein said fatty acid is about C15 to about C18, or (iii) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof. In a second embodiment, the invention provides an antimicrobial composition comprising (I) a pharmaceutically acceptable excipient and (II) an isolated compound of formula; H H I I (1) CH 3 (CH 2 ) 8 -C = C-(CH 2 ) 4 — R 1 - H H I I (2) CH 3 (CH2) 8 - ■ c=c- (CH^e FT wherein R 1 and R 2 are independently (a) CH 2 NR 11 R 12 , wherein R 11 and R 12 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(O)- R 13 , wherein R 13 is (i) NR 14 R 15 , wherein R 14 and R 15 are independently hydrogen or C1 to C6 hydrocarbon, (ii) OR 16 , wherein R 16 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (iii) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof. The compositions of the first and second embodiments have a number of preferred or alternative embodiments. In one preferred embodiment, the compound is according to one of the following formulas H H I I (3) CH 3 (CH 2 ) 5 - C = C - (CH 2 ) 7 — R 3 ; (1) CH 3 (CH 2 ) 8 -C ϊ = C V-(CH 2 )„— R 4 - 1 and mixtures thereof, wherein n is an integer from 3 to 6 and R 3 and R 4 are independently as set forth for R 5 , or a pharmaceutically acceptable salt thereof. Preferably, the compound is of one of the following formulas H H I I (1) CH 3 (CH 2 ) 8 -C==C-(CH 2 ) 4 _ R - H H (2) CH 3 (CH 2 ) 8 -C=C-(CH 2 ) 6 _ R 2 ; H H I I (3) CH 3 (CH 2 ) 5 - C = C — (CH 2 ) 7 _ R 3 j wherein R 1 , R 2 and R 3 are independently (d) CH 2 NR 21 R 22 , (e) C(0)-R 13" , wherein R 13' is (i) OR 26 or (n) a hydroxyl, or (f) CH 2 OH, or a pharmaceutically acceptable salt thereof. In one embodiment, the compound is an ester with a monoglyceπde having a mono- or di- unsaturated fatty acyl component. In another embodiment, the compound comprises an acid whereby R 1 , R 2 or R 3 comprises COOH, or a pharmaceutically acceptable salt thereof. In another embodiment, the salt comprises a sodium, ammonium, silver, copper, calcium, barium, zinc or mono-, di- , tπ- or quaterniary alkylammonium salt, wherein said alkyl substituents on ammonium are independently C1 to C8. Preferably, the alkyl substituents on ammonium are independently C1 to C4 alkyl groups The compositions of the invention can be formulated for a device for dwelling on the skin, such as a wound dressing, ostomy device, IV tape, or the like Preferably, such devices comprise a hydrocolloid gel The compositions of the invention can be adapted for application to an epithelial surface of a mammal For instance, the composition can be a toothpaste, mouthwash, shampoo, hair styling composition, skin ointment, make-up composition, anti-oderant or antipersperant The compositions of the invention can be used to treat or prevent an infection of the gastrointestinal tract comprising administering an antimicrobially effective amount of an antimicrobial composition of the invention In particular, the infection to be treated or prevented can be a Helicobacter pylori infection The compositions of the invention can be used to treat or prevent acne by administering an antimicrobially effective amount of an antimicrobial composition of the invention Preferably, the amount of the antimicrobial composition administered is effective to kill or inhibit the replication of Propionibacteπum The compositions of the invention can be used to preventing the adherence of a microbe to epithelial surfaces comprising administering a microbe adherence reducing effective amount of such an antimicrobial composition The invention further provides a lipid-replenishing skin treatment ointment comprising (a) the antimicrobial composition of claim 1 , and (b) a plurality of lipids selected from the pids normally present on skin The compositions of the invention can be adapted for topical or oral administration, such as a cream adapted for topical administration In a third embodiment, the invention provides a method of treating or preventing infection, the method comprising applying or administering to an animal a composition comprising an antimicrobially effective amount of a compound selected from the group consisting of H H I I (4) CH 3 (CH 2 ) 8 - C =: C- (CH 2 ) n _ R 4 - wherein n is an integer from 3 to 6 and R 4 is (a) CH 2 NR 31 R 32 , wherein R 31 and R 32 are independently hydrogen or C 1 to C6 hydrocarbon, (b) C(O)-R 33 , wherein R 33 is (i) NR 34 R 35 , wherein R 34 and R 35 are independently hydrogen or C 1 to C6 hydrocarbon, (n) OR 36 , wherein R 36 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C 1 5 to about C 1 8, or (in) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt of said compound In a fourth embodiment, the invention provides a method of treating or preventing infection, comprising- (A) administering or applying is to an epithelial surface of an animal a compound as follows (5) CH 3 (CH 2 ) a - C V = V C- (CH 2 ) b _ R 5 - i wherein a + b equals from 1 1 to 1 4 and b is an integer from 1 to 1 4, wherein R 5 is as set forth above, or a pharmaceutically acceptable salt thereof, and (B) applying or administering to the surface an antimicrobial activity enhancing effective amount of a component selected from the group consisting of (C2-C7) alkyl alcohols, polyfalkylene oxιde)s wherein the alkylene moieties are C2 to C4, and mixtures thereof The methods of the third and fourth embodiments have a number of preferred or alternative embodiments. In one preferred embodiment, the compound applied or administered is according to one of the following formulas H H I I (1 ) CH 3 (CH 2 ) 8 - C = C- (CH 2 ) 4 — R 1 - (2) CH 3 (CH 2 ) 8 - C = C- (CH 2 ) 6 _ R 2 ; wherein R 1 and R 2 are independently (d) CH 2 NR 21 R 22 , (e) C(0)-R 1 3 ' , or (f) CH 2 OH, or a pharmaceutically acceptable salt thereof. All of the preferred or alternative embodiments described above for the compositions are, of course, applicable to these methods. In one embodiment, the infection to be treated or prevented is caused by gram negative bacteria. In another embodiment, the infection to be treated or prevented is caused by a drug-resistant microbe, such as a drug-resistant bacteria, which can be a MRSA. In another embodiment, the infection to be treated or prevented is caused by a fungus. The treatment and prevention methods of the invention can also be used to prevent the adherence of a microbe to epithelial surfaces. In one preferred embodiment, the component is applied prior to the compound of formula ( 5) . In a fifth embodiment, the invention provides transdermal administration forms and methods . Thus, the invention provides a transdermal administration form for a biological agent comprising : (a) a bioactive agent; and (b) a transdermal transport effective amount of a compound as follows: H H I I (5) CH 3 (CH 2 ) £ C = C- (CH 2 ) b _ R 5. wherein a + b equals from 1 1 to 1 4 and b is an integer from 1 to 1 4, wherein R 5 is as set forth above, or a pharmaceutically acceptable salt thereof. The method of transdermal administration of a biological agent comprises the steps of: (a) topically applying a biological agent to a site on an animal; and (b) applying to the site a transdermal transport effective amount of a compound as follows: H H I I (5) CH 3 (CH 2 ) a -C ==C- (CH 2 ) b _ R 5 - i wherein a + b equals from 1 1 to 1 4 and b is an integer from 1 to 1 4, wherein R 5 is as set forth above, or a pharmaceutically acceptable salt thereof. Preferably, the applying step (b) occurs prior to or concurrently with applying step (a) . In a sixth embodiment, the invention provides a preservation method and preserved materials. Accordingly, the invention provides a method of preserving a biologically degradable composition comprising contacting the composition with a preservation effective amount of a a compound as follows: (5) CH 3 (CH 2 ) a -C = C- (CH 2 ) b _ R 5 - wherein a + b equals from 1 1 to 1 4 and b is an integer from 1 to 14, wherein R 5 is as set forth above, or a pharmaceutically acceptable salt thereof. The invention also provides preserved compositions comprising the product of the method. Of course, all embodiments of the invention can be modified in accordance with any of the applicable preferred or alternative embodiments. Definitions The terms or phrases listed below shall have the following meaning: • antimicrobial activity encompasses killing microbes, inhibiting the reproduction of microbes, and inhibiting the adherence of microbes to animal tissue. • An antimicrobially effective amount of a compound of formulas ( 1 )-(5) is an amount effective to either (a) reduce the symptoms of a microbial disease sought to be treated, (b) induce a pharmacological change relevant to treating a microbial disease sought to be treated, (c) inhibit or prevent infection or re-infection by a microbial agent, or (d) reduce the adherence of a microbial agent to a tissue. Since the compositions of the inventions can accentuate the activity compounds of formulas ( 1 )-(5), an antimicrobially effective amount is an amount effective when delivered in the relevant composition. For wound treatment, in one aspect, an effective amount includes an amount which, if regularly applied, prevents the occurrence of infection. • a bioactive agent is an agent that is useful for diagnosing or imaging or that can act on a cell, organ or organism, including but not limited to drugs (pharmaceuticals) to create a change in the functioning of the cell, organ or organism. Such agents can include but are not limited to nucleic acids, polynucleotides, antibacterial agents, antiviral agents, antifungal agents, anti-parasitic agents, tumoricidal or anti-cancer agents, proteins, toxins, enzymes, hormones, neurotransmitters, glycoproteins, immunoglobulins, immunomodulators, dyes, radiolabels, radio-opaque compounds, fluorescent compounds, polysaccharides, cell receptor binding molecules, anti-inflammatories, anti-glaucomic agents, mydriatic compounds and local anesthetics. • an excipient is an inert substance used as a diluent or carrier for a pharmaceutically active substance. • an ionizable group is a moiety that is predominantly in an ionized form at physiological pH. • an isolated compound is a compound having at least about 60% wt/wt purity. • a microbe is a bacteria, mycoplasma, yeast or fungi, virus or parasite (such as a malaria parasite) . • a microbe adherence inhibiting effective amount of a compound is an amount that causes a reduction in the portion of a defined inoculum of a microbe that adheres to a tissue to which the microbe normally adheres • oral administration includes any administration into the gastrointestinal tract, including rectal administration • a substantially purified compound shall be one that has a purity of at least about 85% wt/wt • topical administration includes administration to the tissues that form a barrier between the external environment and the internal organs of an animal, including without limitation administration to the skin, gums, buccal tissue, nasal and sinus tissue, ocular tissue, mtraurethral tissue, rectal tissue or intravaginal tissue • a transdermal transport effective amount of a compound shall be an amount of the compound that leads to an increase in the amount of a topically applied biological agent that reaches the blood stream of an animal to which the biological agent was applied. Brief Description of the Drawings Figure 1 shows a schematic for a synthesis of C 1 6 1 Δ6 Figure 2 shows a timecourse for the adherence of C albicans to stratum corneum Figure 3 shows the adherence activity of various Candida isolates Figure 4 shows the adherence of C albicans to stratum corneum, stratum corneum with added skin li id, and lipid depleted stratum corneum Figure 5 shows the effect of adding various fractions of skin lipid to stratum corneum discs Figure 6 shows the effect of adding C 1 6 1 Δ6 and C 1 6 1 Δ9 to stratum corneum discs Figure 7 shows the bacteriocidal activity C 1 6 : 1 Δ6 against 5. aureus. Detailed Description In preferred embodiments, compositions containing a fatty acid or derivative of formulas ( 1 )-( 5) comprise a substantially purified fatty acid or derivative of formulas ( 1 )-( 5) Preferably, the fatty acid or derivative shall comprise at least about 0 01 % wt/wt of the composition More preferably the fatty acid or derivative will comprise at least about 0 05 % of the composition, still more preferably at least about 0. 1 % . In preferred embodiments of the pharmaceutical composition embodiments of the invention, the composition includes a compound of formulas ( 1 )-( 5) that lacks an tonizable group in the R 1 , R 2 , R 3 , R 4 , or R 5 group, but which is convertible to an tonizable group by either a hydrolysis or oxidation reaction. Preferably, the compound is convertible by a hydrolysis reaction Also preferably, the compound is converted to an acid, or a salt thereof More preferably, the convertible compound is an ester of an acid Preferred fatty acids or derivatives for use in the invention will have a primary dermal irritation index of less than about 2 PDI I grade when 0 2 mg of fatty acid or derivative is applied to a 1 0 cm 2 portion of a rabbit ear, more preferably less than about 1 PDII grade under these conditions A suitable non-irritating diluent for use in comparative irritation measurements comprises a gel ointment of 2.5% hydroxypropyl methylcellulose in a water/alcohol mixture comprising from 5 to 75 % of an alcohol such as ethanol or propanol. The gel can contain other suitable exipients or carriers. For topical creams or ointments, preferably the compounds of formulas ( 1 ) - ( 5) will comprise between about 0 1 % and 5.0% (w/v) of the composition , more preferably between about 0 3% and 3.0% , still more preferably between about 0 4% and 1 0% . The compositions of the invention can be administered to an animal such as a human in need of protection from microorganisms or of treatment for an infection Typical modes of administration will include topical, oral, parenteral or pulmonary (by use of an aerosol) administration The compositions can be administered alone, or they can be combined with a pharmaceutically-acceptable excipient according to standard pharmaceutical practice For pulmonary administration, excipients will be selected to be appropriate to allow the formation of an aerosol For the oral mode of administration, the fatty acids and derivatives of the invention are used in the form of tablets, capsules, lozenges, chewing gum, troches, powders, syrups, elixirs, aqueous solutions and suspensions, and the like In the case of tablets, carriers that is used include lactose, sodium citrate and salts of phosphoric acid Various dismtegrants such as starch, and lubricating agents such as magnesium stearate and talc, are commonly used in tablets For oral administration in capsule form, useful diluents are lactose and high molecular weight polyethylene glycols If desired, certain sweetening and/or flavoring agents are added For parenteral administration, sterile solutions of the fatty acids and derivatives of the invention are usually prepared, and the pHs of the solutions are suitably adjusted and buffered For ocular administration, ointments or droppable liquids may be delivered by ocular delivery systems known to the art such as applicators or eye droppers Such compositions can include mucomimetics such as hyaluronic acid , chondroitin sulfate, hydroxypropyl methylcellulose (e g , available from Dow Chemical, Midlands, Ml) or polyvinyl alcohol, preservatives such as sorbic acid, EDTA or benzylchronium chloride, and the usual quantities of diluents and/or carriers For pulmonary administration, diluents and/or carriers will be selected to be appropriate to allow the formation of an aerosol Typical excipients or carriers used for topical creams or ointments include hydrophilic gums such as gelatin, sodium carboxymethylcellulose, pectin, hydroxypropylmethylcellulose and alginates Suppository forms of the fatty acids and derivatives of the invention are useful for vaginal, urethral and rectal administrations Such suppositories will generally be constructed of a mixture of substances that is solid at room temperature but melts at body temperature The substances commonly used to create such vehicles include theobroma oil, glyceπnated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weighty and fatty acid esters of polyethylene glycol See, Remington's Pharmaceutical Sciences, 1 6th Ed , Mack Publishing, Easton, PA, 1 980, pp 1 530- 1 533 for further discussion of suppository dosage forms Analogous gels or creams can be used for vaginal, urethral and rectal administrations Numerous administration vehicles will be apparent to those of ordinary skill in the art, including without limitation slow release formulations, posormal formulations and polymeric matrices The compositions of the invention are preferably administered via devices for dwelling on the skin such as wound dressings, ostomy devices, IV tapes, and the like For wound dressings, the wound dressing will preferably be designed to administer to the wound or adjacent skin an antimicrobial effective amount c f a compound of formulas ( 1 ) (5) Examples of suitable dressings a-e found, for example, in U S Patent Nos 4,909, 243, 4, 538, 603, 5, 244,457 and 5,308,31 3 In one embodiment, the compositions of the invention are formulated in hydrocolloid gels Such gels typically include water soluble hydrocolloids such as pectin, gelatin, guar gum, locust bean gum, gum karaya, and mixtures thereof Pectin and gelatin are preferred For treating or preventing acne, the invention is believed to function by limiting the growth of bacteria or limiting the skin adherence of bacteria, where the bacteria is associated with the formation of acne lesions. One such species of bacteria involved in the formation of acne lesions is Propionibacterium acnes. The invention, particularly the embodiments comprising a component in the composition of the invention, also provides for the treatment or prevention of gram negative infections or infections by microbes that have acquired drug resistance, such as methacillin resistant Staphy/ococcυs aυreus ("MRSA") . Preferred gram negative targets for treatment or prevention include Pseudomonas infections, such as those caused by P. acidovorans, P. aeruginosa, P. cepacia, P. diminuta, P. fluorescens, P. maltophilia, P. pseudoalcaligenes, P. pseudomallei, P. pyocyanea and P. stutzeri, Escherichia infections such as those caused by E. co/i, Serratia infections such as those caused by S. marcescens and Klebsiella infections. Preferred parasite targets for treatment or prevention include Echinococcus infections. Preferred fungal treatment or prevention targets include for example Candida fungi such as C. Albicans, Pityrosporum fungi such as P. ovale or P. orbiculore, Trichosporon funge such as T. rubrυmi, T. tonurans or T. interigitale, Microsporum fungi such as M. canis or M. aυdouinii, Aspergillus fungi, Pyrenochaeta fungi, Scopulariopsis fungi such as S. brevicaulis and Acrononium fungi. All of the above-recited fungi are classified as yeast. For inhibiting the adherence of microbes, the preferred tissues for treatment with the anti-adherence compounds of the invention are skin, stomach, urinary tract, and intravagmal tissues. Skin is most preferred. For lipid-replenishing ointments, the ointment will generally comprise no more than about 5 % (wt/wt) of a compound according to formula (5) . Preferably, the ointment will comprise no more than about 1 % of a compound according to formula (5) , more preferably, no more than about 0.5% . The transdermal administration form of the invention can be used to administer biological agents across any of the several barrier tissues separating the outside environment from the internal organs, including without limitation the skin, gums, buccal tissue, rectal tissue, nasal tissue and sinus membranes In the transdermal transport method, the compounds of formulas ( 1 )-(5) can be applied to the subject before, concurrently with, or after the application of the biological agent that is to be transdermally administered The animals to be treated with the various compositions of the invention are preferably mammals, particularly humans. The invention encompasses using a cream or ointment according to the invention in conjunction with ostomy products For instance, a cream of the invention can be used to coat the face plates or seals on ostomy products See, for example, U.S. Patent Nos. 4,465,486, 4,490, 1 45, 4,460,363 and 4,826,493. The invention further encompasses using the fatty acids or derivatives as additives to antimicrobial compositions that further include other active agents such as antimicrobials (such as antibiotics, including bacitracm) , antifungal agents (such as miconazole and tπconazole) , spermicidals (such as nonoxynol-9), and the like. The compositions of the invention are preferably formulated to have pH less than about 7, to minimize irritation to the treatment subject The component of the invention is preferably a (C2-C7) alkyl alcohol or a polyf alkylene oxide) wherein the alkylene moieties are C2 to C4, or mixtures of alcohol and polyfalkylene oxide) Preferably, the alcohol is C2-C4, more preferably C3, still more preferably isopropanol The alkylene of the polyfalkylene oxide) is preferably C2 C3 The polyfalkylene oxide) can be a copolymer of differing alkylene subunits Isopropyl alcohol is a preferred alcoholic component used with the invention. Preferred alkyleneoxide polymers include those with ethyleneoxide or propyleneoxide polymer building blocks such as polyethylene glycol and polypropylene glycol. The average molecular weight of the polymer is preferably between about 400 and about 1 ,000, more preferably between about 400 and about 800. Various weight-range polymer compositions can be mixed to obtain the consistency desired for a particular composition. Compositions of fatty acid-related compounds according to formulas ( 1 )-(5) and an alcoholic component have the following preferred compositions: Compositions of fatty acid-related compounds according to formulas ( 1 )- (5) and a polymeric component have the following preferred compositions: Compositions of fatty acid-related compounds according to formulas ( 1 )- (5), an alcoholic component and a polymeric component have the following preferred compositions: The syntheses of C 1 6 1 Δ6 and C 1 8: 1 Δ8 were conducted by the same method The C 1 6 1 Δ6 synthesis is outlined in Figure 1 . As a first step in synthesizing C 1 6 1 Δ6, 1 -chloro-5-pentadecyne was synthesized by reacting 1 -chloro-4-bromo-butane with undecyne Second, the 1 -chloro-5 pentadecyne intermediate produced by the first reaction was reacted with potassium cyanide to replace the chloro radical with a cyano radical Third, this nitπle intermediate was reacted with a methanolic mixture of HCI and sulfuric acid to create methyl-6- hexadecynoate Fourth, the methyl ester produced by the third reaction was hydrolyzed to create 6-hexadecynoιc acid Fifth, the acid was reduced by catalytic hydrogenation using a palladium on barium sulfate catalyst to create 6(Z)-hexadecanoιc acid (C 1 6. 1 Δ6) (having cis configuration at the double bond) For the first synthesis step, the solvent conditions must be sufficiently basic to favor proton abstraction from decyne. A mixture of ammonia and NaNH 2 in tetrahydrofuran is a preferred reaction medium Temperatures that are low enough to maintain the ammonia in liquid form are preferred The undecyne (for example, from Lancaster Co. , Windham, NH) is added to the basic solvent incrementally. Then, the akylhalide (or comparable alkyl compound that is σ, rj-dι-substιtuted with an appropriate leaving group) is added incrementally to the reaction These incremental additions of reactants prevent over rigorous reaction For a description of this type of reactnon, see, Sprecher, "The Organic Synthesis of U saturated Fatty Acids," Prog Chem Fats other Lipids 1 5 21 9 254, 1 978 For the second synthesis step, the solvent is preferably anhydrous and aprotic Preferably, the solvent is also polar Dimethylsulfoxide ("DMSO") is a preferred solvent Potassium cyanide is the preferred source of cyanide anion For the third reaction, the nitπle functionality is converted to a carboxylate functionality This can be accomplished by a hydrolytic reaction, such as using acidic or basic hydrolytic conditions, as will be recognized by those of ordinary skill Preferably, the hydrolysis is accomplished in an acidic, alcoholic solvent Particularly preferred is a mixture of methanolic HCI and concentrated H 2 S0 4 These preferred conditions will generate the alcohol ester derivative of the nitπle If the third reaction generates an ester, the fourth reaction comprises a hydrolysis reaction Conditions effective to hydrolyze an ester are well known to those of ordinary skill One such method is base-catalyzed hydrolysis, for instance using 0 5% wt/v NaOH in a mixture of 1 00 ml H 2 0 and 300 ml methanol (which is added to increase the solubility of the ester) Generally, ester hydrolyses proceed at a modest temperature, such as room temperature For the final reaction, the catalyst is preferably palladium on barium sulfate (for example, 5% palladium on sulfate from Aldπch Chemical Co , Milwaukee, WI) The solvent is selected to "poison" the catalyst to adjust its reactivity Pyridine and quinoline are appropriate solvent components for so adjusting catalyst reactivity Anhydous pyridine is the preferred solvent It will be apparent that these synthetic methods can be modified by substituting the starting materials to make other acids within formulas ( 1 ) - (5) The amine compounds of formulas ( 1 ) - (5) can be synthesized, for example by reducing the corresponding amides with a hydride as described, for example, in Section 4 1 of Carey and Sundberg, Advanced Organic Chemistry, Part B, Plenum Press, New York, 1 977 or by Hoffmann rearrangement to remove the carbonyl moiety, as described in Wallis and Lane, Org. React. 3: 267, 1 946. The amide compounds of formulas ( 1 ) - (5) can be synthesized, for instance, by conducting a dehydration reaction between the corresponding fatty acid and NHR 1 R 15 . Such a reaction can be conducted by first forming an activated derivative of the acid such as an anhydride or an N-hydroxysuccinimide ester. Alternately, the dehydration reaction can be conducted using a carbodiimide compound to form a reactive intermediate with the acid moiety. Alternatively, the acid synthesized as described above can be converted to the acid halide, for instance by reaction with a halogen gas in the presence of phosphorus or with a halogen-substituted phosphorus compound such as phosphorus trichloride, and subsequently reacted with the amine moiety. In converting an acid to the acid halide, care should be taken to limit σ-halogenation. The ester compounds of formulas ( 1 ) - (5) wherein R 1 , R , R 3 , R 4 , or R 5 is an ester with glycerol or monoglyceride or can be formed using the same dehydration reactions described above. The alcohol compounds of formulas ( 1 ) - (5) wherein R 1 , R R 3 , R 4 , or R 5 is CH 2 OH can be synthesized by reducing the corresponding esters with a hydride as described, for example, in Section 4. 1 of Carey and Sundberg, Advanced Organic Chemistry, Part B, Plenum Press, New York, 1 977. The following examples further illustrate the present invention, but of course, should not be construed as in any way limiting its scope. Example 1 - Synthesis of 6(Z)-Hexadecanoic Acid 1 -bromo-4-chlorobutane, tetrahydrofuran ("THF") and sodium amide were from Aldrich (Milwaukee, WI); undecyne was from Lancaster (Windham, NH) and anhydrous ammonia was from MG Industries (Messer Griesheim Industries, Malvern, PA) . (THF may require redistillation to limit the peroxide content. ) All glassware was oven dried and cooled under dry N 2 . A stir bar and 200 ml dry THF were placed into a 500 ml three necked flask fitted with a cold trap, a nitrogen inlet, and a mineral oil bubbler. The flask was cooled to -78 ° C in a solid carbon dioxide (dry ice)-acetone bath . A mixture of dry ice and acetone was also used to cool the cold trap. Ammonia ( 1 00 ml) was condensed in the cold trap. The ammonia was then condensed into the flask and 1 2 g (0.3 mol) of NaNH 2 was added under N 2 , creating a milky white mixture. To this mixture 38 ml (30 g, 0.2 mol) undecyne was added dropwise over a 1 0 minute period . The mixture then became thick and viscous . Additional THF was added (70 ml) to reduce the viscosity and allow continued stirring . After stirring for 30 minutes, 25 g (0. 1 45 mol) of 1 -bromo-4-chlorobutane was added dropwise to the mixture over a 1 hour period . This mixture was stirred for an additional 3 hours at -78 ° C, and then allowed to warm and reflux for an additional 2 hours. The reaction was monitored by silica gel TLC developed in 1 00% petroleum ether. In this TLC system undecyne migrates with the solvent front, bromochlorobutane migrates with an RF of 0.60, although it stains only lightly with iodine or charring . The product has an RF of 0.66. No other spots were observed . The reaction mixture was then allowed to gradually warm to 25 ° C and stirred under positive nitrogen pressure for 1 5 hours . After this, the reaction was quenched by the addition of 20 g NH 4 CI . The reaction mixture was then poured into 200 ml cold deionized (" Dl " ) water and 200 ml hexane was added to the resulting mixture . The organic layer was separated , and the aqueous layer was extracted twice more with 1 00 ml hexane. The combined organic layers were washed ( 1 ) with 200 ml Dl water and ( 2) with 200 ml brine (i .e. , an aqueous solution saturated with sodium chloride at 25 ° C) . The washed organic layer was dried over Na 2 S0 4 and filtered . The solvent was removed under vacuum, and the product isolated by vacuum distillation. At 5 mm Hg the excess undecyne distilled off at a temperature between 46-54 ° C. The pure 1 -chloro-4-pentadecyne product distilled at a temperature between 138-144°C. The yield was 19.4 g (0.080 mol) purified 1 -chloro-4-pentadecyne or 55%. In a 1 L flask fitted with a thermometer and a stirring bar, 20 g (.031 mol) KCN (Fisher) was suspended in 400 ml anhydrous DMSO (Aldπch). (Caution, KCN in DMSO is extremely toxic and readily absorbed through skin). 1-chloro-4-pentadecyne (19.4 g) was added and the mixture gradually heated to 98 ° C until reaction completion as monitored by silica gel TLC. (Product RF is 0.43 in 100% pet. ether). When the reaction was complete (after about 3 hours), 200 ml Dl water and 200 ml hexane were added. The organic layer was separated, and the aqueous layer extracted twice more with 150 ml portions of hexane. The combined organic layers were washed twice with 100 ml portions of Dl water and once with 100 mL brine. The washed organic layer was dried over Na 2 S0 4 and the solvent removed in vacuo. The yield was 18.1 g (94%) of straw-colored oil containing 1 -chloro-4-pentadecyne that was used without further purification. The straw-colored oil was added to a 1 L flask, fitted with a condenser and drying tube, containing 400 ml of 2.0 M methanolic HCI. Concentrated H 2 S0 4 (10 ml) was added and the mixture was brought to reflux with stirring. The solution was refluxed until the reaction was complete as monitored by silica gel TLC. (Product RF is 0.81 in 70:30 pet. ether ("PE"): ethyl ether ("EE"); starting material RF is 0.65). Additional concentrated H 2 S0 4 (10 ml) was added daily. The reaction produced several side products. Upon completion (after five days), 200 ml Dl water were added, and the mixture extracted with three 200 ml portions of hexane. The combined organic layers were washed with 200 ml water, 200 ml 5% (w/v) aqueous sodium bicarbonate, and 200 ml brine. The washed organic layer was then dried over Na 2 S0 4 , filtered and the solvent evaporated in vacuo. The resulting crude reddish oil was purified by flash column chromatography (5 x 4 cm, Sιlιco-60, from EM Science , Cherry Hill, NJ) with elution by 85: 1 5 PE : EE . 1 2.6 g ( 57 % yield) of methyl-6-hexadecynoate was recovered as a colorless oil . The methyl ester product was converted to the corresponding acid by refluxing it in a solution of 20 g NaOH dissolved in 300 ml methanol and 1 00 ml Dl water for 3 hours or until completion as measured by silica gel TLC (RF for free acid is 0.35 in 70: 30: 2 PE: EE :acetιc acid) . Upon reaction completion about V. of the methanol was removed in vacuo. The mixture was then acidified with concentrated HCI to a pH of under 3. This mixture was then extracted with 3 x 1 50 ml portions of hexane. The combined organic extract was washed with 1 50 ml Dl water and 1 50 ml brine, and dried over Na 2 S0 4 . The solvent was removed in vacuo to give a quantitative yield of 6-hexadecynoic acid as an oil (Optionally, the product can be recrystallized at 20 ° C from hexane to yield white crystals (M . P. 37 ° C) . However, the recrystal zation results in only 70% recovery and may be omitted) . The 6-hexadecynoιc acid was added to a 1 L flask with 300 ml anhydrous pyridine (Aldrich) along with 1 .0 g of 5 % Pd on BaS0 4 catalyst (oxidized from) and sealed with a rubber septum. The catalyst is available from Aldrich Chemical Co. , Milwaukee, WI . The flask (which was vented with a needle vent) was first purged with nitrogen then hydrogen through a needle cannula . The flask was kept under 2 lbs. positive H 2 pressure, and the reaction monitored by the uptake of hydrogen . When H 2 uptake had ceased the completion of the reaction was analyzed by gas chromatography (SP2330 column, Supelco, Inc , Bellefonte, PA) of an esterified sample. Hydrogen uptake had essentially ceased after 3 hours. However, the reaction was continued overnight. Then, the flask was purged with nitrogen . After which, the catalyst was removed by filtration . The pyridine was then removed under vacuum The final purification was by column chromatography with a 5 x 50 cm Sιlιca-60 column . The column was equilibrated with 90. 1 0 PE . EE The crude product was applied to the column following acidification with 1 ml acetic acid The column was developed step- wise with 500 ml 90 1 0 PE EE, 500 ml 80- 20 PE. EE, and 500 ml 70 30 PE . EE The fractions containing pure 6 hexadecanoic acid (by TLC) were pooled and evaporated A final yield of 7.6 g pure 6(Z)- hexadecanoic acid was isolated with an additional 5 g of impure product ( 90% desired product) retained for repuπfication. The purified product was analyzed by silica gel TLC run in 70 30 2 PE EE ' acetic acid using palmitoleic acid as a reference standard TLC indicated greater than 99% purity. Analytical nuclear magnetic resonance ( " NM R") spectroscopy showed a multiplet pattern indicative of a predominately cis configuration of the double bond . Example 2 - Synthesis of 8(Z)-Hexadecanoic Acid . The same procedures that were outlined above were used except 1 -chloro-6-bromohexane was substituted for 1 -chloro-4- bromobutane. In the first reaction, 20.4 g of 1 -chloro-6-heptadecyne was recovered The 1 chloro 6-heptadecyne product had a boiling point at 5 mm Hg of 1 52- 1 57 ° C. The second reaction produced about 1 8 g of 1 -cyano-6-heptadecyne The fourth reaction produced 1 8. 1 g or 6(Z)-octadecynoιc acid . In the final reductive reaction, the catalyst was replaced to allow the reduction to go to completion. The purified yield of 8(Z)-octadecenoιc acid was 9.6 g TLC indicated greater than 99 % purity. NMR indicated a cis configuration of the carbon-carbon double bond Gas chromatography, using the methyl ester derivative, indicated that 96.5 % of the product had cis configuration Oleic acid (9Z) and elaidic acid (9E) were used as gas chromatography standards Example 3 - Adherence Assay To obtain stratum corneum tissue, immediately after slaughter pigs were shaved and a heated aluminum cylinder ( 65 ° C) was applied to the skin for 30 seconds A corresponding circular section of epidermis was then peeled from the underlying connective tissue and , if not immediately processed further, stored at -20 ° C until use Ten such circular sheets o f epidermis were placed in 1 00 ml of 0 5% trypsin (Type II I , Sigma Chemical Co , St Louis, MO) in 20 mM phosphate buffered isotonic saline ( " PBS" ) at pH 7 4 The epidermis was incubated with the trypsin overnight at 4 ° C The digested tissue was then rinsed with distilled water and placed in a fresh trypsin solution and incubated at 37 ° C for two hours with gentle agitation The resulting stratum corneum was rinsed with distilled water and blotted dry One cm discs of stratum corneum were cut for use in the experiments outlined below The stratum corneum discs were sterilized by autoclaving before storage and use 1 cm discs of stratum corneum were suspended in 1 ml of a suspension of C Albicans fungi containing 5 x 1 0 5 cells per ml In a prior study, the yeast suspension was incubated with the stratum corneum with gentile agitation for from 0 to 3 hours These initial studies indicated that an incubation time of 2 hours was suitable Accordingly, the suspensions were incubated for 2 hours with gentle agitation provided by a rotary shaker The discs were then transferred to clean test tubes and rinsed three times with 5 ml portions of PBS After rinsing, the discs were placed on glass slides and stained with periodic acid Schif f reagent The slides were examined through a microscope and the stained, attached organisms in ten randomly selected fields were counted , and the number averaged A time course for the adherence of Candida albicans to skin is shown in Fig 2 Example 4 - Adherence of Various Candida Strains Three strains of human pathogenic Candida fungi (HPI 1 , HPI 2 and HPI 3) (isolated from symptomatic patients) , one candidal strain of human commensurate (i e , symbiotic, non pathogenic) fungi (HCI 1 ) (isolated from asymptomatic individual) , and a laboratory, non- pathogenic strain, Candida parasitosis were tested for their ability to adhere to stratum corneum using the method outlined in Example 3 The results, measured after 2 hours incubation of the fungus with stratum corneum, were as illustrated in Fig 3 Example 5 - Effects of Lipid Removal and Addition The effect of removing or adding skin hpids to skin on the ability of C albicans to adhere to skin was measured Stratum corneum discs were pid-deleted by successive extractions with chloroform methanol solutions having the following ratios 2 1 , 1 1 and 1 2 (v v) Each extraction was conducted at room temperature for two hours with gentle agitation The discs were air dried overnight For use in adding additional lipid to skin, a ethanol extract of surface skin lipid was prepared as described in Wertz et al , J Invest Dermatol 84 410-41 2, 1 985 Briefly, human volunteers positioned the wrist portions of their arms over a stainless steel basin, with the hand and the rest of the arm angled up and away from the basin A 250 ml portion of 95% ethanol was slowly poured over each wrist and the lipids that extracted into the ethanol were recovered by evaporating the solvent To add skin lipids to stratum corneum discs, the total lipid fraction so isolated was dissolved in hexane isopropanol, 3 2, at a concentration of 1 mg/ml and 50 μl portions (0 05 mg lipid) were applied to stratum corneum discs The solvent was then evaporated from the discs Samples of normal stratum corneum ("sc"), lipid depleted stratum corneum ("-lipid") , and stratum corneum containing additional lipid (" + lιpιd") were tested for the ability of C albicans to adhere thereto, as described in Example 3 The results are shown in Example 6 - Addition of Specific Skin Lipid Fractions to Stratum corneum A part of the skin lipid extract described in Example 5 was fractionated on a preparative (0 25 mm thick) silica gel plate (Adsorbosil plus one ® , Alltech Associates, Deerfield, IL) developed with hexane ethyl ether acetic acid, 70.30 1 (v.v) Lipid fractions were located using a scanning photodensitometer set at 21 0 nm The lipid-containing regions of the plate were scrapped and the lipids eluted using chloroform:methanol water, 50: 50 1 . By this method, fractions containing ( 1 ) squalene ("SQ"), (2) wax esters and cholesterol esters ( "WE/CE"), (3) triglycerides ( "TG"), (4) fatty acids (" FA"), (5) cholesterol ("CH") and (6) a polar fraction made up primarily of ceramides and cholesterol sulfate ("POLAR") were isolated. Using the same methodology outlined in Example 5, the specific lipid fractions described above were added to stratum corneum and the adherence of C. albicans was measured The results are shown in Figure 5. Example 7 - Inhibition of C. albicans adherence by C 1 6 : 1 Δ6 and C 1 6 : 1 Δ9 Using the methodology of Example 5, 0 1 , 1 0 and 1 0 0 mg of C 1 6. 1 Δ6 or C 1 6 1 Δ9 was applied to 1 cm stratum corneum discs and the effect of adherence by C albicans was measured The results are shown in Figure 6 Example 8 - Effect of Lipid on Bacteria A preparation of skin surface lipid prepared by extracting human hair clippings with chloroform methanol, 2 1 , for 2 hours at room temperature Following the extraction, the lipids were recovered by evaporating the extraction solvent The lipids of hair clippings are believed to reflect the composition of sebum free of lipid derived from sweat gland secretions The skin pids or other lipid preparations were suspended or dissolved in beef heart infusion broth (BHIB, Difco, Livonia, Ml) by soπication (taking care not to overheat the broth) Bacteria ( 1 0 8 colony forming units ("CFU") per ml) were suspended in beef heart infusion broth, with or without lipid, and incubated at 37 ' C with agitation. After various intervals, samples were taken from the incubations, diluted and plated on BHIB agar plates to determine the number of colony forming units ("CFUs") present. The results were measured by the number of CFUs versus time. Using this same methodology, the lipid extracted from skin has been shown to be bacteriocidal towards S. aureus, Streptococcus salivarius, Eichinella corodens and Fυsobacteriυm nucleatum (a gram negative anaerobic bacteria involved in gum disease), and to be bacteriostatic (i.e. , to prevent growth) against E. fascalis. Activity was not detected against P. aeruginosa. Example 9 - Inhibitory Activity of Specific Lipids The procedures of Example 8 were repeated using specific fatty acids and testing against both 5. aureus and S. salivarius. In this experiment, the optical density of the cultures was used to indicate the relative numbers of bacteria present, rather than measuring CFU values. The results, in terms of minimum inhibitory concentrations ( " MICs") were as follows: The underlying data for C 1 6 : 1 Δ6 against 5. aureus are shown in Figure 7. Example 10 - Effect of Lipid and Alcohol on Methicillin-Resistant 5. aureus The effects of palmitoleic acid and ethanol ( 1 5%) on methicillin-resistant S. Aureus (MRSA) were tested using the methodology of Example 8. The results, shown as the log of the colony forming units (cfus) measured by plating after 5 minutes exposure, were as follows for a first MRSA strain: The results, shown as the log of the colony forming units (cfus) measured by plating after 5 minutes exposure, were as follows for a second MRSA strain: Example 1 1 - The Primary Dermal Irritation Index for Specific Compositions The primary dermal irritation index ("PDII") of various compositions, each formulated in 2.5% hydroxypropylmethylcellulose in 3: 1 ethanol: water, was measured using an albino rabbit, single insult patch test. Two test areas per rabbit were prepared by shaving both areas, and abrading one of the areas. Similarly, two matching control areas were prepared on each animal. The test material, 0.5 ml each application, was applied to 2.5 x 2.5 cm gauze patches, and held against the test area with an impervious Vetrap brand bandage (3M, St. Paul, MN) . The patches were held in place for 24 h, at which time the treatment sites were wiped clean. The evaluations were based on observations at this 24 h timepoint and on observations at the 72 h timepoint. Scoring was as set forth in Draize, "Dermal Toxicity, " Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity, pp. 46-59, Association of Food and Drug Officials of the U.S. , Topeka, Kansas, 1 965. The results for individual fatty acids were as follows: Example 12 - A Further Test for Antimicrobial Activity A drop of bacteria suspended in PBS, containing 3 x 1 0 5 bacteria, was deposited on a sterilized Whatman filter No. 4 (4.4 cm 2 ). A gel composition containing a prospective antimicrobial agent was layered over the filter paper, with care taken to avoid air pockets formed between the gel and the filter. This amount of bacteria is in excess of the amount ( 1 x 1 0 5 ) considered to constitute an infection when present in one gram of tissue. The filters with bacteria and gel compositions were maintained at room temperature for 20 minutes. The filters were then placed in 25 ml of Trypticase Soy Broth Z-49 medium (available from GIBCO (Grand Island, NY) and incubated in a shaker incubator for 24 hours at 38 6 ° C at 1 32 rpm. Positive results were scored when bacteria could not be observed microscopically in the culture medium Example 1 3 - Various Formulations The following formulations, described in weight percentages, were prepared 1 The polyethylene glycol was PEG-400, available from Aldrich Chemical Co , Milwaukee, WI. 2 The gelatin was obtained from Hormel, Davenport, IA 3 The pectin was obtained from Citrus Colloids, Hereford, United Kingdom Compositions 1 , 3 and 4 were transparent liquids Composition 2 was a liquid when freshly prepared, but subsequently separated into two phases Compositions 5 and 6 were gels Example 14 - Various Formulations The following formulations, described in weight percentages, were prepared 1 The sodium carboxymethylcellulose (NaCMC) was from Aqualon Ltd. , Warrington, United Kingdom. All of the above-described compositions 6- 10 are gels. Example 1 5 - Test Results Composition 1 0 and a corresponding composition 1 0-CMP, which lacked the fatty acid component, were tested for antimicrobial activity against E. co// using the method of Example 1 2. The following average optical densities were obtained for cultures grown from filters treated as indicated : While this invention has been described with an emphasis upon preferred embodiments, it will be obvious to those of ordinary skil in the art that variations in the preferred devices and methods may be used and that it is intended that the invention may be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications encompassed within the spirit and scope of the invention as defined by the claims that follow.

Claims: What is claimed: 1. An antimicrobial composition comprising (A) antimicrobial activity enhancing effective amount of a component selected from the group consisting of (C2-C7) alkyl alcohols, polyfalkylene oxιde)s wherein the alkylene moieties are C2 to C4, and mixtures thereof; and (B) a compound as follows: (5) CH 3 (CH 2 ) a -C = C-(CH 2 ) b _ R 5 - wherein a + b equals from 11 to 14 and b is an integer from 1 to 14, and wherein R 5 is (a) CH 2 NR 21 R 22 , wherein R 21 and R 22 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(0)-R 23 , wherein R 23 is (i) NR 24 R 2 . 5 , wherein R 24 and R 25 are independently hydrogen or C1 to C6 hydrocarbon, (ii) OR 26 , wherein R 26 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (iii) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof. 2. The composition of claim 1 , wherein the compound of formula (5) is according to one of the following formulas H H I l (3) CH 3 (CH 2 ) 5 - C = C - (CH 2 ) 7 _ R 3 ; H H I I (4) CH 3 (CH )---C = C — (CH 2 ) n — R 4 ; and mixtures thereof, wherein n is an integer from 3 to 6 and R 3 and R 4 are independently as set forth for R 5 . 3 The composition of claim 1 , wherein the compound of formula (5) is according to one of the following formulas (1) CH 3 (CH 2 ) 8 -C = C-(CH 2 ) 4 — R 1 - 1 H H (2) CH 3 (CH 2 ) 8 -C=C-(CH 2 ) 6 — R 2 ; H H I I (3) CH 3 (CH 2 ) 5 - C = C — (CH 2 ) 7 _ R 3 • wherein R 1 , R 2 and R 3 are independently (d) CH 2 NR 21 R 22 , (e) C(0)-R 13' wherein R 13' is (i) OR 26 , or (n) a hydroxyl, or (f) CH 2 OH, or a pharmaceutically acceptable salt thereof. 4. The composition of claim 3, wherein the compound comprises an acid whereby R 1 , R 2 or R 3 comprises COOH, or a pharmaceutically acceptable salt thereof. 5. The composition of claim 4, wherein the compound is an acid addition salt and the salt comprises a sodium, ammonium, silver, copper, calcium, barium, zinc or mono-, di- , tπ- or quaterniary alkylammonium salt, wherein said alkyl substituents on ammonium are independently C1 to C8. 6. An antimicrobial composition of claim 1, wherein the composition is a toothpaste, mouthwash, shampoo, hair styling composition, skin ointment, make-up composition, anti-oderant or antipersperant 7 A device for dwelling on the skin comprising the antimicrobial composition of claim 1 8 A method of treating or preventing an infection of the gastrointestinal tract comprising administering an antimicrobially effective amount of the antimicrobial composition according to claim 1 9 A method of treating or preventing an acne comprising administering an antimicrobially effective amount of the antimicrobial composition according to claim 1 1 0 A method of preventing the adherence of a microbe to epithelial surfaces comprising administering a microbe adherence reducing effective amount of an antimicrobial composition according to claim 1 1 1 A lipid-replenishmg skin treatment ointment comprising (a) the antimicrobial composition of claim 1 , and (b) a plurality of lipids selected from the pids normally present on skin 1 2 An antimicrobial composition comprising (I) a pharmaceutically acceptable excipient and (II) an isolated compound of formula H H I I (1 ) CH 3 (CH 2 ) 8 - C = C- (CH 2 ) 4 _ R 1 V V (2) CH 3 (CH 2 ) 8 - C= C- (CH 2 ) 6 — R wherein R 1 and R 2 are independently (a) CH 2 NR 11 R 12 , wherein R 11 and R 12 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(0)-R 13 , wherein R 13 is (i) NR 14 R 15 , wherein R 14 and R 15 are independently hydrogen or C1 to C6 hydrocarbon, (n) OR 16 , wherein R 16 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (in) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof 13. The composition of claim 12, wherein R 1 and R 2 are independently CH 2 NR 11 R 12 , C(0)-R 13' , wherein R 13' is (1) OR 16 , or (2) a hydroxyl; or CH 2 OH, or a pharmaceutically acceptable salt thereof 14. The composition of claim 13, wherein the compound is an acid whereby at least one of R 1 or R 2 is C(0)OH, or a pharmaceutically acceptable salt thereof. 15. The composition of claim 14, wherein the compound is an acid addition salt and the salt comprises a sodium, ammonium, silver, copper, calcium, barium, zinc or mono-, di- , tπ- or quaterniary alkylammonium salt, wherein said alkyl substituents on ammonium are independently C1 to C8 16. The composition of claim 12, wherein further comprises an antimicrobial activity enhancing effective amount of a component selected from the group consisting of (C2-C7) alkyl alcohols, polyfalkylene oxιde)s wherein the alkylene moieties are C2 to C4, and mixtures thereof 17. A method of treating or preventing infection, the method comprising applying or administering to an animal a composition comprising an antimicrobially effective amount of a compound selected from the group consisting of H H I I (4) CH 3 (CH 2 ) 8 -C = C-(CH 2 ) π — R 4 wherein n is an integer from 3 to 6 and R 4 is (a) CH 2 NR 31 R 32 , wherein R 31 and R 32 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(0)-R 33 , wherein R 33 is (i) NR 34 R 35 , wherein R 34 and R 35 are independently hydrogen or C1 to C6 hydrocarbon, (n) OR 36 , wherein R 36 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (in) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt of said compound 18. The method of treating or preventing infection of claim 17, wherein the compound is according to one of the following formulas H H I I (1) CH 3 (CH 2 ) 8 -C = C-(CH 2 ) 4 — R 1 ( (2) CH 3 (CH 2 ) 8 -C Y = C H -(CH 2 ) 6 R wherein R 1 and R 2 are independently (d) CH 2 NR 31 R 32 , (e) C(0)-R 13' wherein R |1 1 3 J* , is„ n OπR>3 J 6 b or (n) a hydroxyl, or (f) CH 2 OH, or a pharmaceutically acceptable salt thereof 19 The method of treating or preventing infection of claim 18, wherein said compound is an acid whereby R 1 or R 2 is C(0)OH, or a pharmaceutically acceptable salt of the acid 20 The method of treating or preventing infection of claim 19, wherein the compound is an acid addition salt of a sodium, ammonium, silver, copper, calcium, barium, zinc or mono-, di- , tπ- or quaterniary alkylammonium, wherein said alkyl substituents on ammonium are independently C 1 to C8. 21 . A method of treating or preventing a microbial infection comprising : (A) administering or applying is to an epithelial surface of an animal a compound as follows : (5) CH 3 (CH 2 ) a - C = C- (CH 2 ) b — R 5- wherein a + b equals from 1 1 to 1 4 and b is an integer from 1 to 1 4, wherein R 5 is (a) CH 2 NR 21 R 22 , wherein R 21 and R 22 are independently hydrogen or C 1 to C6 hydrocarbon, (b) C(0)-R 23 , R 23 is (i) NR 4 R 25 , wherein R 24 and R 25 are " independently hydrogen or C 1 to C6 hydrocarbon, (ii) OR 26 , wherein R 25 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C 1 5 to about C 1 8, or (in) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof; and (B) applying or administering to the surface an antimicrobial activity enhancing effective amount of a component selected from the group consisting of (C2-C7) alkyl alcohols, poly(alkylene oxide)s wherein the alkylene moieties are C2 to C4, and mixtures thereof . 22 The method of treating or preventing an infection of claim 21, wherein the compound of formula (5) is of formula (1), (2) or (3) as follows (1) CH 3 (CH;) 8 -C=C-(CH 2 ) 4 _ R> 1 H H 1 ' (2) CH 3 (CH 2 ) 8 - C= C- (CH 2 ) 6 _ R 2 ( H H I I (3) CH 3 (CH 2 ) 5 -C = C-(CH 2 ) 7 _ R 3- wherein R 1 , R 2 and R 3 are independently (d) CH 2 NR 21 R 22 , (e) C(O) R 13* , wherein R 13* is (i) OR 26 , or (n) a hydroxyl, or (f) CH 2 OH, or a pharmaceutically acceptable salt thereof 23 The method of claim 22, wherein the compound administered or applied comprises an acid whereby R 1 , R 2 or R 3 comprises COOH, or a pharmaceutically acceptable salt thereof 24 The method of treating or preventing infection of claim 23, wherein the compound comprises a sodium, ammonium, silver, copper, calcium, barium, zinc or mono , di- , tπ- or quaterniary alkylammonium acid addition salt, wherein said alkyl substituents on ammonium are independently C1 to C8 25 A transdermal administration form for a bioactive agent comprising (a) the bioactive agent, and (b) a transdermal transport effective amount of a compound as follows H H I I (5) CH 3 (CH 2 ) a -C = C-(CH 2 ) b _ R 5 wherein a + b equals from 11 to 14 and b is an integer from 1 to 14, wherein R 5 is (a) CH 2 NR 21 R 22 , wherein R 21 and R 22 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(0)-R 23 , R 23 is (i) NR 24 R 25 , wherein R 24 and R 25 are independently hydrogen or C1 to C6 hydrocarbon, (u) OR 26 , wherein R 26 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (in) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof 26 A method of transdermal administration of a bioactive agent comprising the steps of (a) topically applying a bioactive agent to a site on an animal, and (b) applying to the site a transdermal transport effective amount of a compound as follows H H I I (5) CH 3 (CH 2 ) a -C = C-(CH 2 ) b _ R 5 ( wherein a + b equals from 11 to 14 and b is an integer from 1 to 14, wherein R 5 is (a) CH 2 NR 1 R 22 , wherein R 21 and R 22 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(0)-R 23 , R 23 is (i) NR 24 R 25 , wherein R 24 and R 25 are independently hydrogen or C1 to C6 hydrocarbon, (n) OR 26 , wherein R 26 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (in) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof. 27. The method of claim 26, wherein the applying step (b) occurs prior to or concurrently with applying step (a) . 28. A method of preserving a biologically degradable composition comprising contacting the composition with a preservation effective amount of a a compound as follows: H H I I (5) cH 3 (CH 2 ) a - C = C- (CH 2 ) b _ R 5 - wherein a + b equals from 1 1 to 1 and b is an integer from 1 to 1 4, wherein R 5 is (a) CH 2 NR 21 R 22 , wherein R 2 1 and R 22 .are independently hydrogen or C 1 to C6 hydrocarbon, (b) C(0)-R 23 , R 23 is (i) NR 24 R 25 , wherein R 24 and R 25 are independently hydrogen or C 1 to C6 hydrocarbon, (ii) OR 26 , wherein R 26 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C 1 5 to about C 1 8, or (iii) a hydroxyl, or (c) CH 2 OH . 29. A preserved composition comprising the product of the method of claim 28.

Inventors: KYDONIEUS AGIS, NJIEHA FRANCOIS K, WERTZ PHILIP W, WILLE JOHN J, KYDONIEUS, AGIS, NJIEHA, FRANCOIS, K., WERTZ, PHILIP, W.;, WILLE, JOHN, J.
Applicants: SQUIBB BRISTOL MYERS CO, BRISTOL-MYERS SQUIBB COMPANY
Application year: 1997
Main classification: A01N25
IPC codes: A01N37, A61K8, A61K31, A61P31, A61Q1, A61Q5, A61Q11, A61Q15, A61Q17, A61Q19