PHARMACEUTICAL PREPARATIONS AND COMPOSITIONS

Abstract: A pharmaceutical composition characterised in that it comprises: (a) vitamin A, (b) one or more tochopherols, (c) an oil of the genus prunus, and (d) an oil of the genus sesamum indicum (L. Pedaliaceae); in that the weight of each of (c) and (d) is between 5 and 75 times the weight of (a); in that the weight of each of (c) and (d) is between 4 and 125 times the weight of (b); and in that the composition has a consistency suitable for topical application.

Description: PHARMACEUTICAL PREPARATIONS AND COMPOSITIONS TECHNICAL FIELD: This invention relates to pharmaceutical preparations and compositions, particularly but not exclusively for external application to provide symptomatic relief of dermatological conditions, e.g. excema, psoriasis, herpes simplex (cold sores) and the like; and their manufacture. DISCLOSURE OF INVENTION: According to this invention there is provided a pharmaceutical composition characterised in that it comprises (a) Vitamin A, (b) one or more tochopherols (c) an oil of the genus prunus, and (d) an oil of the genus sesamum indicum (L. Pedaliaceae); in that the weight of each of (c) and (d) is between 5 and 75 times the weight of (a); in that th weight of each of (c) and (d) is between 4 and 125 times the weight of (b); and in that the composition has a consistency suitable for topical application. Advantageously the ratio of the weight of (a) to (b) is in the range 1:15.5 to 21:1. Preferably the weight of (a) is between 0.75 and 1.8 times the weight of (b). Preferably the weights of (a) and (b) are substantially the same. Preferably the weights of (c) and (d) are substantially the same. Preferably the weight of (c) - or (d) - is approximately 18 to 19 times the weight of (a) and approximately 20 times the weight of (b). In preferred examples of this invention, (c) comprises almond oil and (d) comprises sesame seed oil. OMPI Advantageously said preparation or composition further comprises olive oil, the weight of olive oil being preferably between 9 and 140 times the weight of (a) and/or between 7 and 250 times the weight of (b). Preferably said Vitamin A is in the form of the resin palmitate. BEST MODE OF CARRYING OUT THE INVENTION Various preferred embodiments of this invention will now be described, reference being had to Table A. In all these preferred embodiments of Table A, the Vitamin A employed is in the form of the palmitate resin oil with a strength of 1 x lo International Units per gm of the oil. The palmitate Vitamin A alone has a strength of 1.87 x l0 International Units per gm whence it will be appreciated that the weight figures for constituent (a) in columns I, II, III and IV of Table A correspond respectively 4-10, 2, 10 and 5 ml of the said palmitate resin oil. In these preferred embodiments of Table " A, the Vitamin E employed constitutes and is provided by a mixture of tochopherols - typically 10-14% alpha-tochopherols, 64-76% of a combination of beta-tochopherols and gamma-tochopherols, and 20-30% delta-tochopherols. For the purposes of these examples, the reference to Vitamin E is to be taken as a reference to the whole mixture of tochopherols employed rather than, for example, to just the alpha-tochopherols (which are considered by some authorities to be the essential substance to which the term Vitamin E may be employed). For the composition of column II of Table A, the Vitamin E employed was in an oil form known as T 3 Q J- i.e. having 300mg of tochopherols per ml of oil, and the indicated weight of 0.6g therefore corresponds to 2ml of the oil 3θ« For the composition of column III of Table, the Vitamin E employed was in an oil form known as τ 7n / i.e. having 700mg of tochopherols per ml of oil, and the TABLE A Note : percentage figures shown are approximate indicated weight of 7g therefore corresponds to 10ml of the oil g. For the compositions of columns I and IV of Table A, the Vitamin E employed was in an oil form known as T50 (e.g. that sold under the Trade Mark "COVIOX TSQ"), i.e. having 500mg of tochopherols per ml of oil, and the indicated weights of 2-5g and , 2.5g therefore correspond to respectively 4-10ml and 5ml of the oil T5g» It will be appreciated that in the preferred embodiments of Table A, the almond oil employed is an oil derived from the kernel of a fruit of the genus prunus amygdalus variety "AMARA" or prunus amygdalus variety "DϋLCIS'*, and the sesame seed oil (or sesame oil) employed is an oil derived from the seed of the genus sesamum indicum (L. Pedaliaceae) . In forming each of the embodiments of Table A, all the constituents - in oil form — were added to one another at room temperature and mixed well. The compositions represented by column I of Table A are preparations with preferred ranges of the constituents (a) to (e). The composition of column II of Table A is considered to be a potentially rather weak preparation according to this invention and yet remaining reasonably effective for symptomatic relief of, for example, excema. In contrast, the composition of column III of Table A is considered to be a potentially very strong and effective preparation according to this invention. A particularly preferred preparation according to this invention is the composition set out in column IV of Table A, this composition being currently considered as probably the strongest one which would not be dangerous if taken internally by mistake. From the approximate percentage figures given in Table A it will be noted that: constituent (a) varies between 0.37% and 4.37%, and in preferred composition IV is 1.30%, of the total; constituent (b) varies between 0.21% and 5.72%, and_ preferred composition IV is 1.22%, of the total each of constituents (c) and (d) varies between 23.1% and 26.0% and in the preferred composition IV each constitute 24.4% of the total; and consitutent (e) varies between 40.9% and 51.4%, and in preferred composition IV is 48.9%, of the total. From calculations based on these figures it can be determined (i) that the ratio of constituent (c) or (d) to constituent (a) is between 5.3 and 70.3, i.e. within the range 5 to 75 obtained by appropriate rounding up and down, and is preferably 18.8, i.e. about 18 to 19, (ii) that the ratio of constituent (c) or (d) to constituent (b) is between 4.0 and 123.8, i.e. within the range 4 to 125, and is preferably about 20, (iii) that the ratio of constituent (a) to constituent (b) is in the range 0.06:1 to 21:1, i.e. 1:15.5 to 21:1, and is preferably in the range 0.76:1 to 1.81:1, i.e. about 0.75:1 to 1.8:1, (iv) that this last ratio is 1.07 in the case of preferred composition IV, i.e. the weights of constituents (a) and (b) are substantially the same, (v) that the ratio of constituent (e) to constituent (a) is between 9.24 and 138.9, i.e. within the range 9 to 140 obtained by appropriate, .rounding, up and down, and is 37.6 (i.e. about 37) in the case of preferred composition IV, (vi) that the ratio of constituent (e) to constituent (b) is between 7.15 and 244..8, " i.e. within the range 7 to 250 obtained by appropriate rounding up and down, and is 40.1 (i.e. about 40) in the case of preferred composition IV. The constituents (a) to (e) of each composition may remain in the natural oil-like state obtained by adding them to one another, or they may be emulsified by appropriate emulsifying agents to form a suitable or desired consistency, e.g. of a cream or of an ointment. In tests and experiments conducted to date by applying composition IV to affected areas of the skin, remarkably positive and beneficial results have been noticed. The preparation has proved fast-acting, effective and long-lasting in alleviating the irritation, itching and burning sensations usually ocurring with dermatological conditions such as excema, psoriasis, athlete's foot, herpes simplex, heat bumps, insect bites and the like, as well as with symptoms occurring with haemorrhoids. Moreover, i addition to symptomatic relief, a definite curative resul has been experienced in many instances where the composition has acted to accelerate the body's natural healing ability, e.g. in allowing haemorroids to shrink, or in speeding the formation of scabs on open wounds. In many cases, symptomatic relief for over 8 hours was enjoyed from a single application of composition IV. For example, in a pilot study along the lines of a "double blind" trial, the efficiency of composition IV of Table was tested against (A) cold sores, i.e. herpex simplex labialis, and (B) minor skin irritations. For test (A), ten volunteers with herpes simplex labialis participated on a random basis. Eight volunteers had tw lesions each and acted as their own controls by firs applying composition IV to the larger lesion only. In all eight cases composition IV was applied to the smaller lesio after at least one week without any medication thereto. One of the volunteers with only one lesion agreed not to appl any medication at all. Similarly for test (B), te volunteers with various forms of skin irritations participated on a random basis. All volunteers with eczema or dermatitis agreed to apply composition IV to a marked test area alone for 7 days, thus acting as their ow controls. All cases where spontaneous healing of the untreated area occurred within 7 days were discarded. Written, informed consent was obtained from all volunteers or guardians before tests (A) and (B). The sex, age. - JU complaint, treatment and results associated with each volunteer are tabulated in Table B and its accompanying Notes from which it is clear that said composition IV is most efficacious against herpex simplex labialis and minor skin irritations. TABLE B Results Volunteer Complaint Treatment Treated Untreate Test Number Sex Age Number No. Lesion or Lesion f 1 ) Area or Area (A) 1 M 62 Cl l R3 R8 2 F 27 Cl Tl R3 R8 3 F 21 Cl Tl R4 R8 4 M 67 Cl Tl R3 R8 5 F 18 Cl Tl R3 R8 6 F 45 Cl Tl R4 R8 7 F- 57 Cl Tl R3 R8 8 F 44 C2 Tl R3 R8 9 M 39 C2 T2 R8 10 F 62 C2 T3 R3 (B) 11 F 3 C3 T4 R7 R8 12 F 5 C3 T4 R7 R8 13 F 54 C4 T4 R2 R8 14 F 34 C4 T4 R2 R8 15 F 18 C4 T4 R2 R8 16 F 2 C4 T4 R2 R8 17 M 7 C4 T4 R2 R8 18 F 11 C4 T4 R2 R8 19 M 24 C5 T3 R4 20 F 25 C5 T3 R3 Notes Tl = Composition IV (of Table A) M = Male applied to larger lesion F = Female immediately and to smaller lesion after 1 week. Cl = 2 herpes simplex lesions T2 = None C2 = 1 herpex simplex lesion T3 = Composition IV (of Table A) C3 = dermatitis applied to the 1 lesion. C4 = eczema T4 = Composition IV (of Table A) C5 = herpangina applied to marked test area. R2 = Healed after 2 days i 1 ) All lesions healed within R3 = Healed after 3 days 5 days after treatment with R4 = Healed after 4 days Composition IV (of Table A) R7 = Healed after 3 days but relapse 4 initiated. days after treatment stopped. R8 = Accute inflamatory changes still present after 8 days. TABLE C From other experimental tests conducted (see Table C) it appears that all four constituents (a) to (d) are necessary to achieve appreciable relief. Where one of the vitamins (A or E) is omitted from the composition (test 2 or 3 in Table C) the beneficial effects are severly curtailed and only minimal relief is obtained. Omission of either almond oil or sesame seed oil (test 4 or 5 in Table C) causes a similar depreciation of the relief obtainable and leaves just a burning sensation. The trials and experiments clearly show a synergistic effect with all four constituents (a) to (d). The provision of constituent (e), i.e. the olive ' oil, increases substantially the long-lasting nature of the relief provided by the composition. (see test ' 6 in Table C). Although the reason for such a surprising synergistic effect is not known, it is thought possible that, notwithstanding the vegetable-oil-like characteristics of constituents (c), (d) and (e), the composition as a whole could act as an inhibitor of the lipoxygenase enzyme to inhibit production of inflammatory leukotrienes, i.e. the lipoxygenase etabolits of arachidonic acid (which are generally found in vegetable oils), and which are thought to cause psoriasis and kindred dermatological disorders. According to another aspect of this invention there is provided a method of manufacturing a pharmaceutical composition, said method being characterised in that it comprises admixing to one another: (a) Vitamin A, (b) one or more tochopherols (c) an oil of the genus prunus, and (d) an oil of the genus sesamum indicum (L. Pedaliaceae); in that the weight of each of (c) and (d) is between 5 and 75 times the weight of (a); in that the weight of each of (c) and (d) is between 4 and 125 times the weight of (b); and in that the composition has a consistency suitable for topical application. INDUSTRIAL APPLICABILITY From the foregoing it will be appreciated that this invention is capable of widespread exploitation in the pharmaceutical and ethical chemical industry, and in medicine.

Claims: CLAIMS 1. A pharmaceutical composition characterised in that it comprises (a) Vitamin A, (b) one or more tochopherols (c) an oil of the genus prunus, and (d) an oil of the genus sesamum indicum (L. Pedaliaceae); in that the weight of each of (c) and (d) is between 5 and 75 times the weight of (a); in that the weight of each of (c) and (d) is between 4 and 125 times the weight of (b); and in that the composition has a consistency suitable for topical application. 2. A pharmaceutical composition according to Claim 1, characterised in that the ratio of the weight of constituent (a) to constituent (b) is within the range 1:15.5 to 21:1. 3. A pharmaceutical composition according to Claim 1 or Claim 2, characterised in that the weight of constituent (a) is between 0.75 and 1.8 times the weight of constituent (b). 4. A pharmaceutical composition according to any preceding Claim, characterised in that the weight of constituents (c) and (d) are substantially the same. 5. A pharmaceutical composition according to any preceding • Claim, characterised in that the weights of constituents (a) and (b) are substantially the same. 6. A pharmaceutical composition according to any one of Claims 1 to 3, characterised in that the weight of constituent (c) is substanitally the same as the weight - .2 - of constituent (d) and is approximately 18 to 19 times the weight of consituent (a), and approximately 20 times the weight of constituent (b). 7. A pharmaceutical composition according to any preceding Claim, characterised in that constituent (c) comprises almond oil. 8. A pharmaceutical composition according to any preceding Claim, characterised in that constituent (d) comprises sesame seed oil. 9. A pharmaceutical composition according to any preceding Claim, characterised in that it further comprises olive oil. 10. A pharmaceutical composition according to Claim 9, characterised in that the weight of olive oil is between 9 and 140 times the. weight of constituent (a) and/or between 7 and 250 times the weight of constituent (b). 11. A pharmaceutical composition according to Claim 9 or Claim 10, characterised in that the weight of olive oil is approximately 37 to 40 times the weight of each of the constituents (a) and (b). 12. A pharmaceutical composition according to any preceding Claim, characterised in that it comprises (a) 1.0 to 5.4 parts by weight Vitamin A (b) 0.6 to 7.0 parts by weight Vitamin E (c) 30 to 70 parts by weight Almond oil (d) 30 to 70 parts by weight Sesame Seed Oil, and (e) 50 to 150 parts by weight Olive Oil. - ξj E 13. A pharmaceutical composition according to any precedi Claim, characterised in that it comprises (a) 2.7 parts by weight Vitamin A (b) 2.5 parts by weight Vitamin E (c) 50 parts by weight Almond Oil (d) 50 parts by weight Sesame Seed Oil (e) 100 parts by weight Olive Oil. 14. A pharmaceutical composition according to any precedi Claim, characterised in that said Vitamin A is in th form of the resin palmitate. 15. A method of manufacturing a pharmaceutical composition said method being characterised in that it comprise admixing to one another; (a) Vitamin A, (b) one or more tochopherols (c) an oil of the genus prunus, and (d) an oil of the genus sesamum indicurn (L Pedaliaceae) ; in that the weight of each of (c) and (d) is between and 75 times the weight of (a); in that the weight o each of (c) and (d) is between 4 and 125 times th weight of (b) ; and in that the composition has consistency suitable for topical application. 16. A method according to Claim 15, characterised i that the ratio of the weight of constituent (a) t constituent (b) is within the range 1:15.5 to 21:1. 17. A method according to Claim 15 or Claim 16, characterised in that the weight of constituent (a) is between 0.75 and 1.8 times the weight of constituen 18. A method according to any one of Claims 15 to 1 characterised in that the weight of constituents ( and (d) are substantially the same. 19. A method according to any one of Claims 15 to 1 characterised in that the weights of constituents ( and (b) are substantially the same. 20. A method according to any one of Claims 15 17, characterised in that the weight of constituent ( is substantially the same as the weight of constitue (d) and is approximately 18 to 19 times the weight -—-" consituent (a), and approximately 20 times the weig of constituent (b) . 21. A method according to any one of Claims 15 to 2 characterised, in that constituent (c) comprises almo oil. 22. A method according to any one of Claims 15 to 21 characterised in that constituent (d) comprises sesa seed oil. 23. A method according to any one of Claims 15 to 22 characterised by the further admixture of olive oil. 24. A method according to Claim 23, characterised i that the weight of olive oil is between 9 and 140 time the weight of constituent (a) and/or between 7 and 25 times the weight of constituent (b) . 25. A method according to Claim 23 or Claim 24 characterised in that the weight of olive oil i approximately 37 to 40 times the weight of each of th constituents (a) and (b) . - | 5 - 26. A method according to any one of Claims 15 to 25, characterised in that it comprises (a) 1.0 to 5.4 parts by weight Vitamin A (b) 0.6 to 7.0 parts by weight Vitamin E (c) 30 to 70 parts by weight Almond oil (d) 30 to 70 parts by weight Sesame Seed Oil, and (e) 50 to 150 parts by weight Olive Oil. 27. A method according to any one of Claims 15 to 26, characterised in that it comprises (a) 2.7 parts by weight Vitamin A (b) 2.5 parts by weight Vitamin E (c) 50 parts by weight Almond Oil (d) 50 parts by weight Sesame Seed Oil (e) 100 parts by weight Olive Oil. 28. A method according to any one of Claim 15 to 27, characterised i_α that said Vitamin A is in the form of the resin palmitate. O

Inventors: ROCKE DENNIS, ROCKE, DENNIS
Applicants: ROCKE DENNIS, ROCKE, DENNIS
Application year: 1982
Main classification: A61K35
IPC codes: A61K8, A61K31, A61K36, A61K38, A61Q19