LV13450B - Novel medicinal use of meldonium and pharmaceutical compositions thereof - Google Patents

Abstract

The present invention relates to new uses of meldonium in medicine. It is useful for treatment of skin and tissue injuries as well as for treatment of skin irritation. Pharmaceutical compositions for topical use containing meldonium are also disclosed. These compositions substantially improve process of healing wounds, inhibit allergic and other origin skin irritation. Therefore they can be useful for treatment and prevention of skin and outer tissue injuries of different origin.

Description

-1- LV 13450

Use of Meldonium for the treatment of tissue damage / wound and local / local skin irritation and suitable compositions.

The invention relates to a novel medical application (3- medical use of propionate 3- (2,2,2-trimethylhydrazinium) propionate) for the treatment of tissue damage / wound and local / local skin irritation and compositions containing it.

Tissue damage / wound healing is a rather complicated process, accompanied by allergic or other skin irritation, which, as a rule, is a difficult task to stimulate. Usually, various pharmaceutical compositions are used to heal tissue damage / wounds, the main purpose of which is to provide wound sterility. For this purpose, ointments, gels, creams, etc. containing antibacterials (antibiotics, silver preparations, etc.) are used. However, these agents only reduce the healing time of infected wounds, but do not affect or even brake the healing of uninfected wounds. As a second drawback to such pharmaceutical preparations and their compositions, mention should be made of their toxicity if the topical / topical application form is to be applied to a large surface area, which is due to the absorption of large amounts of antibiotics in the body through the surface of the damaged tissue. Damaged tissues usually also develop an allergic or other inflammatory reaction that is not prevented by antibacterials.

There are known forms of external use that are used to promote wound healing and whose mechanism of action is related to the regulation of the rate of certain metabolic processes. These include, for example, 6-methyluracil, 6-oxymethyluracil (pentoxyl), and dexpanthenol (INN) (+ 2,4-dioxo-N- (3-oxypropyl) -3,3-dimethylbutiroamide) or soloceryl. The action of dexpanthenol is based on the formation of pantothenic acid in the body, which promotes cellular mitosis and increases the resistance of collagen fibers, thus stimulating tissue healing / wound healing. However, this preparation is very poorly soluble in physiological fluids and the positive effect of dexpanthenol at 25 is exorbitant (patent DE531260). The same applies to uracil derivatives whose local application forms are based on water-insoluble bases. As a rule, exudate retraction caused by water-insoluble ointments or other forms of external application of the drug creates favorable preconditions for microbial development in wounds. In addition, uracil derivatives also cause dyspepsia. To overcome some of the problems associated with the use of poorly water-soluble preparations for wound healing, it is necessary to develop technologically more sophisticated compositions, such as combining water-insoluble substances with cyclodextrin and / or cellulose derivatives to form water-dispersible forms which are further mixed with water-2- soluble ointments or gel bases (RU 2155586 C 2, RU 2149007 Cl). This greatly complicates the technological process of producing external-topical formulations and poses significant problems in standardization and stability of ointments.

In turn, the Soloseril's ointment, which is made from deproteinised calf blood plasma, is a potential source of danger due to the risk of rabies infection of the Jacob-Creutzfeld type cows. The object of the present invention was therefore to find tissue damage / wound healing medications that are high in toxicity and good water solubility to be safe for use in large tissues or skin lesions, to prevent allergic or other irritations, and whose forms of treatment are easy to prepare and stable storage and compatible with potentially diverse ointment base components, antibacterial agents, and other additives required for tissue damage / wound therapy.

The purpose of the invention was unexpectedly achieved by using meldonium as a pharmacologically active substance.

It is well known that Meldonium in its dihydrate form is widely used as a substance that regulates the ratio of the concentrations of chitin and gamma-butyrobetaine in the body and hence the rate of beta-oxidation of fatty acids (Dambrova M., Liepinsh E., Kalvinsh I. Mildronate: cardioprotective action through camitine-lovvering effect .. Review. // Trends Cardiovasc.Med. - 2002 - Vol. 12, N.6 - P. 275-279. Group H, Zarain-Herzberg A., Maisch B. The use of partial Fatty Acid oxidation inhibitor for metabolic therapy of angina pectoris and heart failure // Herz, 2002. Vol. 27, N.7 - P. 621-636. Mildronate, Met-88 Drugs Run 2001, 26 (1) ), p.82).

Thanks to these features, meldonium (with the registered trademarks "MILDRONĀTS ® MILDRONATE®, MHJTJļPOHAT®") is widely used in medicine as an anti-ischemic and stress-controlling agent for various cardiovascular diseases and other pathologies associated with tissue excretion. (PCKapnoB, 0.A.KomejitCKaa, ABBpy6.neBCKHH, AACokojiob, ATTenjiaKOB, H.CKap / ia, B./fjepBe / LIGHHitape, A.BHTOJic, y.KaJiHHHbui, H.KajihHbiu, JI.MaTBea hHHHHecica οφφεκτΗΒΗοσπ. h 6e3onacHocTb MHnzHiHaTnNiNeNeHUH xpoHHMecKofi cepneuHOH HeflocTaTOHHocTH y 6ojibHbix HmeMHHecKOH 6ojie3HbK) cepzuuua. Kapanonorna, 2000, Vol.6, - P.69-74.) (English: RSKarpov, OAKosheIskaya, AVVrublevsky, AASokolov, ATTeplyakov, I.Skarda, V.Dzērve, D.Klintsare, A.Vitol, -3- LV 13450 I.Kalvinsh, L.Matveyeva, D.Ubanbane, Clinical efficacy and safety of patients with ischemic heart disease and chronic heart failure., Kardiologiya, 2000, Vol.6, - P.69-74.) . Since the Meldonium molecule contains a trimethylammonium group, it was expected that the substance would be absorbed poorly through the skin. However, we have unexpectedly discovered that meldonium, used externally,, however, significantly stimulates tissue healing / wound healing, as well as removing allergic or other skin irritations such as rash or skin damage caused by neurodermatitis. Our finding that the Meldonium pharmaceutical compositions for external use stimulate tissue damage / wound healing processes and does not cause (suppress) allergic or other skin tissue irritation can not be explained by the effect of Meldonium on the cardiovascular system based on the reduction of chitin levels in tissues. We discovered that meldonium in the form of ointment, cream, gel, emulsion, lotion, foam spray or solution stimulates the process of tissue damage / wound healing, which can be experimentally determined by the improvement of the following indicators due to meldonium in tissue damage / wound healing: 15 - after absolute wound size decrease in wound healing rate, - after wound area decreases during the day, - after regeneration rate increase, - after regeneration regression increase, 20 - after complete healing time of wound, - after maturation of connective tissue and faster wound healing process. Thus, we succeeded in showing that Meldonium compositions at their external application significantly improve tissue healing / wound healing speed and normalize the healing processes taking place, stimulating not only the healing process itself, but also promoting maturation of the connective tissue and improving the visual appearance of tissue damage / wound.

This is particularly true for complicated tissue damage / wound healing, i. originated from chemical burns, thermal burns, mixed burns, deep wounds, etc.

Meldonium can be used to produce various types of external topical pharmaceutical compositions. In this case, the composition consists of meldonium concentrations of 0.5 - 40% by weight, optimally 10-12% and ointment, cream, gel, emulsion, oil, liniment, milk, lotion, foam - 4 - aerosol or solution base suitable and pharmaceutically acceptable. ingredients. Compositions are made with such a calculation to ensure that their reaction ranges from pH 4-8.

If necessary, other components such as enzymes, dermatological agents, insect replicates, fragrances, dyes or aromatic oils are added to the above compositions.

For example, one of the possible pharmaceutical compositions illustrating the present invention but not limiting it is the following composition:

Ingredients Meldonum Gel Base Meldonum Gel 10% Meldonium Gel 5% Meldonium Gel 2.5% Meldonium Spray Meldonium 0.00 10.00 5.00 2.50 5.00 Sodium Glycolate Starch, Type C. Mark. Vivastar® P5000 4.00 4.00 4.00 4.00 X Propylene glycol 2.00 2.00 2.00 2.00 3-5 Fumaric acid 0.08 0.40 0.20 0.10 X Methyl parahydroxybenzoate 0.16 0.16 0.16 0.16 X Propyl parahydroxybenzoate 0.04 0.04 0.04 0.04 X Purified water 93.72 83.40 88.60 89.2 Other pH 4.54 5.23 5.04 5.19 Ketanol XXXX 0, 0 5-1.5 Ethanol XXXX 8 Propelents XXXX 3-6 " abula. No.1

The Meldonium Efficacy Assessment can be characterized by the following typical example of the effect of different gel concentration of meldonium on the ulcer healing process -5-

Experiments were performed on male Wistar rats (body weight 185-210 g). 80 white rats were used in the experiment. The animals were kept in accordance with their welfare requirements, fed with standard feed, appropriate standards (Mackta J. Inspecting the Process: A Collaborative Approach to Improving Animal Care, Lab. Animal 2000, 29, 10, 32-534).

In order to induce aseptic inflammation, 0.5 ml of a 9% acetic acid solution was administered to animals in the right fore-cast under the light ether anesthesia. At the same time, 300 mg / kg dextran was injected into the abdominal cavity in a 6% solution, which contributed to the inflammatory process by releasing histamine. 10 The ulcer at the injection site started after 2-3 days. After 4 days almost all animals had ulcers. We selected 50 animals with homogeneous ulcers around which there was also local skin irritation.

We started the treatment of animals with Meldonium gel on day 4, applying it at the prescribed time every day twice a day instead of the ulcer. Experiment duration 25 days. Animals were divided into 5 groups of 10 individuals per group: Group I - Control Group - Healing of ulcers occurs naturally; Group II - Experimental, ulcer treatment with Meldonum Gel Base Mass; Group III- Experimental, ulcer treatment with 10% Meldonium gel; Group IV - Experimental, ulcer treatment with 5% Meldonium gel; Group 20 V - Experimental, ulcer treatment with 2.5% Meldonium gel.

Every fourth day, the control and experimental group animals were visually evaluated for ulcer healing rates - we evaluated the appearance of the ulcer, the feeling of pain in the ulcer area, the rate of scab formation and separation, the skin temperature, as well as the presence of local / local allergic and / or other skin irritation. We felt the feeling of pain by touching the skin with a wooden swab in the 25 areas. We evaluated the ulcer healing rate (V) according to the following formula:

So-St vV ~ = 100 x-

So where So - ulcer size before treatment (mm2); St - size of ulcer on the day of measurement (mm2). 30 -6-

The recovery process is characterized by an enhanced epithelial process and we used two indicators to measure it: the regeneration factor (Rkoef) and the regeneration regression (Rrcu) indicator:

This

Rkoer S t; regeneration rate in the experiment;

Rreg Regeneration Rate Controlled After 12 days, 3 animals from each group of light ether anesthesia were decapitated and the respective skin piece in the ulcer area was removed. The ulcer healing process was evaluated for all groups within 24 days. References in the literature by various authors indicate that herbal remedies: ointments, gels and so on. can create better conditions for the healing of ulcers, but the healing process is relatively difficult to stimulate (Pam > i h paHeea ΗΗφεκηκΗ / pen. Ky3HHa M.H., ΚοσποΗβΗοκ E.M./ «Me / umnHa», 1990, p. -7- EN 13450 A significant difference between the control and experimental groups treated with the meldonium gel was observed at the rate of ulcer healing. Healing compositions with different Meldonium content significantly accelerated the tissue lesion / wound healing process (tab.2.3). 5 The effect of Meldonum gel on the experiment of the skin cell reparative process

Group of animals Average size of ulcers (mm2) before treatment Day 20 24-day Vid.chūlu Chūls Regen- Regene- Warmed Vid.chule ulcers Regeneration- Regeneration - hernia size healing rhythm ulcers healing radius (mm2) nas ratio regression count (mm2) speed (V) factor regression number speed (R-factor) 0W)% (Rkocf) (Rrcg ·) (V)% control 221.0 33.0 +85.0 3.57 ± 0 0, 00 1/7 28.0 87.3.04 ± 0 0 2/7 ± 48.1 ± 12.2 ± 11.2 Base Mass 133.1 54.3 +59.2 2.33 ± 1.75 0 , 35 2/7 51.3 61.5 12.73 ± 10.27 0.33 3/7 ± .70.5 ± 37.8 ± 21.2 Meldonium 215.5 6.6 +96.9 18, 50 + 16,73 * 4,7 4/7 all ulcers all ulcers all 7/7 10% ± 154.8 ± 5.0 / 13.4 * ulcers healed healed ulcers healed healed meldonium 304.7 15.0 +95, 0 26.29 ± 24.87x 2.9 3/7 7.75 97.5 30.07 ± 0.94x 4.97 5/7 5% ± 140.3 ± 11.5 / 8.3 * ± 2.52 / 15 , 1 * Meldonium 154.3 16.0 +89.6 16.06 ± 8.34x 1.4 2/7 10.0 93.5 15.40 ± 5.9X 1.95 5/7 2.5% ± 61.6 ± 12.8 / 3.9 * ± 4, 32 / 5.9 * 10 15 20 P < 0.05

Table 2

During the experiment, it was observed that during ulcer healing, allergic and other irritation zones were observed around the ulcers of Group I and II on all skin ulcers, where only about 3 ulcers were observed in Group V, and only about 2 ulcers in Group IV; there are no sources of irritation. If the meldonium 10% gel is applied to an irritant site, it disappears within 1-2 days. -8-

Morphological Study Day 24 Experiment Using Meldonium Gel For Experimental Ulcer Treatment 10 15

Group Multiple Edema Under Flat Epithelium Epithelium New connective tissues cover the intensity of morphological feature of all ulcers / number of animals with the observed feature morphological sign intensity Polyblast Fibroblast Fibrocyte Indicator / Number of animals with the found feature layer layer Control ++ / 1 + / 3 ++ / 2 ++ + / 3 + / 1 going +12 +++ / 1 0/2 healing process Gel basic ++ I2 ++ / 2 ++ I2 +++ I3 + / 1 mass + / 1 0/1 +++ / 1 0/2 healing process 10% meldo- +++ / 3 0/3 0/3 + / 1 +++ / 3 healing nail gel 0/2 process finished 5% meldo- +++ / 3 + / 3 0/3 + / 1 + / 2 healing nail gel 0/2 0/1 process continues 2.5% meldo- +++ I2 + / 3 + / 1 -H- / 3 ++ / 2 healing nail gel ++ / 1 0/2 0/1 process continues

Table No.3 ΡΟ.05 20

Note: + - low intensity of morphological trait; ++ - Moderate; +++ - Intense; 0 is not found

Compared to the control group, the experimental animals in the ulcer area are also significantly less painful, characterized by a more relaxed behavior of the animals during the touch in the ulcer area and less sensitivity of the skin. The results of the morphological study of histological material taken on day 24 of the experiment are summarized in Table 3. Morphological discovery shows that significant differences between experimental groups are in the process of maturation of new connective tissue. In groups I and II (control and placebo, or basal gel) under the multi-layered flat epithelium, young connective tissues rich in new cells - polyblasts and fibroblasts - have very little fibrocytes in mature connective tissue cells. Meldonium gel treated groups show impressive connective tissue maturation, control cells very rarely. -9- EN 13450 in histological cuts, mainly fibrocytes, especially in Group III (10% gel of Meldonium). Minor edema occurs in all groups except the group where meldonium 10% gel was used to treat ulcers. Thus, we discovered that Meldonium was used in externally used pharmaceutical compositions, promoted a better tissue damage / scar (including ulcer) healing process compared to a control group and a group that used the base gel gel.

In addition, the results of the study suggest that meldonium is not toxic when applied topically (tissue damage).

Meldonium can be used in pharmaceutical compositions based on a fat-soluble or water-soluble composition. However, greater efficacy in tissue damage / wounds is shown by meldonium water-soluble compositions. Also, compositions in the form of foam showed a good therapeutic effect. We have discovered that meldonium can be used effectively in hard outer forms that swell and form a gel, such as carboxymethylcellulose - wadding, powder, dressing, as a result of wound exudation. self-absorbing materials, such as those that make self-absorbing surgical suture materials, are particularly suitable.

Meldonium external forms of application can be used to treat skin and external tissue lesions of various origins, including but not limited to neurodermitis, fungal skin lesions, burns, effusions, allergic skin lesions, surgical and traumatic wounds, trophic ulcers, and other skin and skin disorders. in case of external tissue damage. In this case, an appropriate antibacterial or antibiotic agent for combatting aerobic and / or anaerobic microflora or combinations thereof that improve the results of treatment of infected wounds such as sulfargine, iodine or others can be added to the composition of the external application form of Meldonium. In order to further enhance the efficacy of Meldonium's external application forms, in some cases, they may be combined with already known tissue damage / wound healing stimulants, such as methyluracil or panthenolol, either alone or in combination. -10-

External (topical) forms of Meldonium for tissue damage / wound and / or allergic and other inflammation / irritation of other origin may be added: non-fluid anti-inflammatory agents such as arylpropionic acid derivatives such as but not limited to ketorprofen, ibuprofen, naproxen, flurbiprofen , alminoprofen, thiaprofenic acid, etc .; steroidal anti-inflammatory drugs such as corticosteroids - prednisolone, prednisone, methylprednisolone, peripheral analgesia or others; topical anesthetics such as novacin, lidocaine, aspirin, diflunisal, ibuprofen, fenoprofen, ketoprofen, floctafenine, noramidopyrine or others; enzymatic wound cleansing preparations such as heparin, trypsin, papain, etc .; imidazole-containing antifungal agents such as miconazole, ketoconazole, fluconazole, flucitosin, griseofulvin or others; beta-lactam antibiotics such as penicillin, cephalosporin, carbapenem, carbacefen, monobactam; macrolide antobiotic groups: erythromycin, azithromycin, oleandomycin, josamycin, spiramycin and roxithromycin; tetracycline antibiotic groups: ositetracycline, morphocycline, etc .; aminoglycoside groups: streptomycin, neomycin, gentamicin, kanamycin, sizomycin, spiramycin, erythromycin, etc .; chloramphenicol or levomycetin: levomycetin, etc .; Cyclic polypeptide or polymyxin groups: capreomycin, etc .; Linkosamide groups: clindamycin and lincomycin, etc .; rifamycin groups: rifampicin, etc., glycopeptide groups: vancomycin, etc .; streptogramin groups: pristinamycin, etc .; sulfanylamide groups such as sulfadiazine; polyene antifungal agents, such as amphotericin B, nystatin, etc .; antiviral agents taken from the group comprising zidovudine, aciclovir, adamantane line preparations such as rimantadine, amantadine and moroxidine, etc .; natural remedies (plant or animal extracts) for healing wounds and fighting inflammation and / or infections, such as onion, plantain, liquorice, or aloe extracts, oat fruit, aloe vera root, Iceland lichen leaf extracts, and extracts of anise fruits, arnica flowers, calendula flowers, chamomile flowers, flax seeds, pearl leaves, yarrow buds, pine buds, raspberry leaves, sage leaves, sea buckthorn fruits, carob spores, fatty rootlets; -11- EN 13450 extracts from natural medicine for pain relief, such as: hop fruit stalks, valerian rhizomes, beladonn leaves, dragonflies, birch puffs, chamomile flowers, poppy seedlings, peppermint leaves, rhizomes, sea buckthorn fruits, ostriches foliage, bullet leaf, etc .; 5 extracts from natural medicine that have antimicrobial and antiparasitic effects, such as arnica flowers, St. John's wort, teddy bear flowers, eucalyptus leaves, Iceland lichen foliage, calendula flowers and herbs, yellow fangs, linden flowers, black oak, pine fruit, pine trees buds, shrub shoots, moorish rare herbs, celandine shoots; bleeding aids: (sponge) collagen (taotope), amben; 10 hemostatic agents: alum, iron chloride, polymylineol, tannins, trichloroacetic acid; blood vessels narrowing adrenomimetics adrenaline and metazaton. non-narcotic analgesic antipyrine; vitamins: A, Bl, B2, B3, B5, B6, B8, Bc, BT, B12, C, D, D2, D-3, D-hormone, E, K, K1, K3, P, P3, P4, PP, U; 15 antihistamines such as Hi blockers taken from the etanalamine group, e.g. clemastine and the like, preparations of the ethylenediamine group, e.g. mepiramine, e.g., alkylamine group drugs such as chlorpheniramine and the like, piperazine groups, e.g., searchozine, etc., phenothiazine groups, e.g. promethazine, etc. or H2 blockers such as cimetidine, ranitidine, nizatidine, etc. ; enzymes, e.g., wobenzyme, flagoenzyme, and mumps and co-enzymes; 20 calcium preparations; carbazohrom; angina-protectors etamsilate and calcium dobesilate; bee products such as propolis, etc .;

Pharmaceutical compositions illustrating but not limiting the invention include the following 25 compositions for gel production: 30 5 -12-

Meldonium Gel Composition: 10 15 FK5 FK6 FK7 FK8 FK9 FK10 FK.ll FK12 Meldonium 0.5-15% 0.5-15% 0.5-15% 0.5-15% 0.5-15% 0.5 -15% 0.5-15% 0.5-15% Chloramphenicol 0.3-1.5% 0% 0% 0% 0% 0.3-1.5% 0% 0% Methyluracil 0.3-5 , 0% 0% 0% 0% 0% 0.3- 5.0% 0% 0% Prednisolone 0% 0% 0, l% -2% 0% 0% 0% 0% 0% Sulphadiazine silver salt 0% 0% 0% 0.5-2% 0% 0% 0.5-2% 0% Dexpanthenol 0% 0% 0% 0 1-7% 1-7% 1-7% Propolis 0% 0% 0% 0 % 0% 0% 0% 1-15% Gel base weight after tab. 1 the rest of the rest the rest of the rest the rest of the rest Purified water 0-15% 0-15% 0-15% 0-15% 0-15% 0-15% 0-15% 0-15%

Table 4

If the wound was infected with microorganisms susceptible to chloramphenicol, sulfadiazine silver salt, quinifuril or propolis, the addition of these antibacterial adhesives to the meldonium outer compositions further improved their efficacy by an average of 10%. Additionally, the addition of dexpanthenol or methyluracil also showed a positive effect on meldonium topical treatment compositions after day 24. In these cases, the efficacy of the combined preparations was 7-8% higher compared to the dexpatenolol or 6-methyluracil groups and 4-5% higher compared to the meldonium topical formulation without dexpanthenol or 6-methyluracil. 30 -13- EN 13450 FK13 FK14 FK15 FK16 Meldonium 0.5-15% 0.5-15% 0.5-15% 0.5-15% Methyluracil 0.3-5.0% 0.3-5, 0% 0% 0% Lidocaine hydrochloride 0.1-3% 0.1-3% 0% 0% Hinifuril (Chinifurylum) 0% 0.1-1% 0% 0% Ketoprofen 0% 0% 1-5% 0 % Vobenzyme 0% 0% 0% 0.5-5% Gel base weight after tab. 1 rest of the rest other cleaned water 0-15% 0-15% 0-15% 0-15%

Pharmaceutical compositions containing meldonium without any local anesthetic agents, non-steroidal or steroidal anti-inflammatory agents, coenzymes, infected wounds improved the efficacy of meldonium-containing gels by an average of 9%. ^ Experimental data suggest that pharmaceutical compositions containing meldonium are non-toxic.

Meldonium emulsion, cream, solution, oil, ointment, liniment, paste, gel, lotion, milk, suspension, powder and foam spray, as well as their compositions with other active ingredients are obtained by well-known techniques. 20 25 30

Claims (15)

-14-INVENTION FORMULA 5 10 15 20 25 EN 13450 1. The use of Meldonium for the manufacture of topical or topical medicaments for the treatment and / or prophylaxis of skin and subcutaneous tissue disorders. 2. The use of Meldonium for the manufacture of topical or topical medicaments for the treatment and / or prophylaxis of local or local skin irritation. 3. A pharmaceutical composition for use in the treatment and prevention of skin, tissue damage and / or for the treatment and prophylaxis of topical / local skin irritation, characterized in that it contains meldonium as an active ingredient and pharmaceutical excipients suitable for external use. 4. A pharmaceutical composition for use in the treatment and / or prophylaxis of skin and tissue lesions and / or for the treatment and / or prophylaxis of topical / local skin irritation comprising meldonium and pharmaceutically acceptable excipients for external use, characterized in that without meldonium it contains at least one or more other active substances, but not more than three taken from the group consisting of natural or synthetic: steroids and non-steroidal anti-inflammatory agents, analgesic and anesthetic agents, antifungal agents, antibacterial agents, antiviral agents, antihistamines, enzymes, co-enzymes, dermatological agents, tissue damage / wound healing agents, bee products. 5. A pharmaceutical composition according to claim 3 or claim 4, wherein the Meldonium content in the composition is from 0.1 to 40% by weight, preferably from 2.5 to 12% by weight. 6. A composition according to claim 3, wherein the excipients are suitable for curative, prophylactic emulsion, cream, solution, oil, ointment, liniment, paste, gel, lotion, milk, suspension, powder, foam spray, cotton wool and dressing. material. 30 -15- 7. A composition according to claim 3 or claim 4 wherein the pH is from 4 to 8 * 8. A composition according to claim 4, wherein the other active ingredient is chloramphenicol. 9. A composition according to claim 4, wherein the other active ingredient is dexpatenol. 10. A composition according to claim 4, wherein the other active ingredient is methyluracil. 11. The composition according to claim 4, wherein the other active ingredient is prednisolone. 12. A composition according to claim 4, wherein the other active ingredient is a sulfadiazine silver salt. 13. A composition according to claim 4, wherein the other active ingredient is lidocaine. 14. The composition according to claim 4, wherein the other active ingredient is quinifuril. 15. A composition according to claim 4, wherein the other active ingredient is propolis. 16. A composition according to claim 4, wherein the other active ingredient is ketoprofen. 17. A composition according to claim 3, wherein hydrophilic excipients are used as pharmaceutical excipients. 18. A composition according to claim 3, wherein hydrophobic excipients are used as pharmaceutical excipients. 19. A composition according to claim 3, wherein hydrophilic excipients are used in combination with hydrophobic excipients as pharmaceutical excipients. 20. A composition according to claims 3 and 4, characterized in that it is an emulsion, cream, solution, oil, ointment, liniment, paste, gel, lotion, milk, suspension, powder, foam spray, cotton wool or dressing material.