MXPA00012069A

MXPA00012069A - Method and composition for the treatment of epidermal irritations and infections

Info

Publication number: MXPA00012069A
Application number: MXPA/A/2000/012069A
Authority: MX
Inventors: J Embro William
Original assignee: Martin Unger
Priority date: 1998-06-09
Filing date: 2000-12-06
Publication date: 2002-07-25

Abstract

An improved stannous fluoride composition is disclosed. The composition comprises stannous fluoride and at least one zinc containing compound. The zinc containing compounds stabilized and prevent hydrolysis of the stannous ions resulting in a more effective stannous fluoride composition for use in the treatment of epidermal irritations and infections.

Description

METHOD AND COMPOSITION FOR THE TREATMENT OF IRRITATIONS AND EPIDERMAL INFECTIONS DESCRIPTION OF THE INVENTION The present invention relates to an improved composition of stannous fluoride for the treatment of skin irritations and infections. Stannous fluoride has been used in dentistry since 1950 to prevent dental cavities. Norman Tinanoff reviews 40 years of human studies of animals 10 having some studies greater efficiency than others in "Review of the Antimicrobial Action of Stannous Floride" (The Journal of Clinical Dentistry Vol. II 1990). U.S. Patent No. 4,097,590"Methods and Compositions for Treatment of Bacteria and Fungus infections of the skin" 15 describes the treatment of vulgaris and athlete's foot with a soluble fluoride salt. The present invention previously determined that stannous fluoride can be used to treat diseases that have a viral etiology. (North American Patent No. 5,098,716 for Embro). 20 Both the shelf life and the antimicrobial effect of a stannous fluoride product depends on the stability of the active stannous ion (Sn + 2). Products formulated for home use achieve stability of the stannous ion by adding glycerin or other insoluble materials in water to reduce hydrolysis and oxidation. The - i-m t t'nrm • 1 -.é "t ^ t-. - ", *", - ". *. * ...-,. . . ....., j -. "," ,,, t. = ^. ^, ...

Aqueous formulations employ chelating agents, which bind the stannous fluoride and create a stagnant receptacle that acts as a supply of stannous ions and an antioxidant. Majeti et al. (US Patent No. 5 5,004,597), developed a dentifrice stabilization system for stannous fluoride by using stannous chloride as an antioxidant with stannous receptacle and sodium gluconate as a chelating agent to protect the stannous fluoride from hydrolysis. Other chemicals used in the Stabilization of stannous fluoride includes polyvinyl alcohol (PVA), tripolyphosphates, vinyl methyl ether copolymers and maleic anhydride. However, the use of these and other complexing agents for the stabilization of stannous fluoride may limit the bioavailability of the stannous ions for a therapeutic effect. In view of the foregoing, there is a need to provide improved stannous fluoride compositions. The present invention relates to an improved stannous fluoride composition comprising stannous fluoride and at least one compound containing zinc. It has been shown that the improved composition is more stable and less toxic than a stannous fluoride composition that does not contain a zinc compound. The inventor has also shown that the improved composition of the invention allows one to decrease the dose of fluoride stannous required to achieve an effect therapeutic It has been shown that the improved composition of the invention is effective in treating epidermal irritations and infections and their symptoms. Accordingly, the present invention also provides a method for treating an epidermal irritation or infection comprising administering an effective amount of a composition comprising stannous fluoride and at least one compound containing zinc to an animal in need thereof. Other features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and specific examples while indicating preferred embodiments of the invention are given. only by way of illustration, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. The present invention relates to a composition of improved stannous fluoride comprising stannous fluoride and at least one compound containing zinc. This composition can be referred to herein as "the composition of the invention". The composition of the invention is remarkably improved on a composition containing stannous fluoride without any zinc compound in several aspects. First, stannous fluoride undergoes hydrolysis and oxidation in aqueous environments resulting in loss of stannous bioavailability due to precipitation 5 of stannous hydroxide. Zinc-containing compounds stabilize stannous fluoride by preventing oxidation and hydrolysis of the stannous ion. Zinc ions have a higher affinity than stannous ions for hydroxides and other anions in aqueous solutions. As a result, the Zinc in the composition of the invention will form complexes with • Hydroxides and will inhibit the hydrolysis and precipitation of stannous ions. In particular, the invention has shown that a solution of stannous fluoride containing zinc gluconate remains stable, without precipitation, for at least 3 months. In contrast, a solution of stannous fluoride without zinc gluconate precipitated extensively. Second, zinc compounds regulate the hydrogen ion in which it promotes high pH. This • makes the composition more suitable for local use since more acidic formulations can irritate or cause a burning sensation on the skin. Third, the present invention has unexpectedly found that zinc compounds act synergistically with and potentiate the activity of stannous fluoride. In particular, it has demonstrated that in the composition of the invention the fluoride Stagnant works better than when the dose is used twice in a composition that does not contain the zinc compounds. Consequently, the dose of the stannous fluoride can be significantly decreased in the composition of the invention resulting in a less toxic composition. As mentioned above, the inclusion of zinc compounds in the composition of the present invention stabilizes and increases the efficiency of stannous fluoride. Use compounds that contain zinc in the composition as well has additional advantages because zinc is widely recognized since it has medicinal and healing properties. In particular, 1) zinc is essential for life; 2) zinc is necessary for more than 100 enzymes (ie, alcohol dehydrogenase carboxypeptidase); 3) zinc keeps body levels of vitamin A; 4) zinc is important in the function of the sexual organ and reproduction; 5) zinc is important for DNA / RNA synthesis; 6) zinc can improve cell-mediated immunity; and 7) zinc • is incorporated into hundreds of dermatological formulas for help maintain healthy skin cells. Using stannous compounds with stannous fluoride will not provide the added benefits of zinc since tin is not essential for life and is not necessary for enzymatic function. 25 The zinc-containing compound can be any , -it ^ it? l? ^ - ^ m, j,. .- - Sfa * - ». "? ~ x- », .... -. .. ^ - -. * .... ... ^ r, .., ^ -.?. - t - »compound containing zinc including zinc carboxylates and zinc salts. The zinc carboxylate is preferably selected from one or more of zinc gluconate, zinc tartrate, zinc malate, zinc propionate, zinc citrate, and zinc acetate. More preferably, the zinc carboxylate is zinc gluconate. The zinc salt is preferably selected from zinc chloride, zinc sulfate, zinc phosphate, zinc pyrophosphate, zinc oxide or zinc thiocyanate. Preferably, the zinc salt is zinc chloride. improved results. Preferably, the stannous fluoride is provided in a concentration ranging from about 0.1 wt% to about 8.0 wt% and zinc gluconate is provided in a concentration ranging from about 0.5 wt% to about 10.0 wt%. More preferably, the composition comprises 0.20% stannous fluoride and 1.5% zinc gluconate, in a non-aqueous medium such as glycerin. The composition may additionally contain zinc chloride in a concentration ranging from about 0.5% by weight to about 5.0% by weight. The addition of zinc chloride may be useful in compositions with a high aqueous content (ie> 80% of water). The composition of the invention may include more than one compound containing zinc. For example, the zinc compound can be zinc gluconate, zinc chloride and / or acetate • zinc The composition may additionally include one of the a, L or D essential or non-essential amino acids selected from the group consisting of lysine, arginine, histidine, phenylalanine, threonine, leucine, isoleucine, cysteine, methionine, valine, alanine, glycine, proline. , glutamine, serine, tryptophan, tyrosine and asparagine.

The composition can be formulated using techniques known in the art for example as described in Remington's Pharmacetical Sciences, Eighteenth Edition, Mark Publishing Company. The composition is preferably a gel, ointment, cream, lotion, spray or the like, suitable for local administration. Advantageously, the composition of the present invention maintains its bioavailability at a pH suitable for local administration. The composition may also include pharmaceutically diluents or carriers acceptable including water, carbopol, glycerin and 9-hydroxymethyl cellulose. The composition of the invention may additionally include excipients known in the art including fillers such as saccharides, for example, Lactose or sucrose, preparations of mannitol or sorbitol cellulose and / or calcium phosphates, for example, tricalcium phosphate or calcium hydrophosphate, as well as binders such as starch paste, using for example, corn starch, wheat starch, starch rice, potato starch, gelatin, tragacanth, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone. In some cases, it may be desirable to add disintegrating agents such as the starches mentioned above and also carboxymethyl starch, cross-linked polyvinylpyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate. The auxiliaries are, above all, agents that regulate the flow and lubricants, for example, silica, talc, spherical acid, or salts thereof, such as magnesium stearate or calcium stearate, and / or polyethylene glycol. The compositions of the invention may contain, as additives, preservatives such as p-hydrobenzoates (nipa esters, methylparaben), sorbic acid, and chlorhexidine gluconate, benzalkonium chloride, and bromide Hexadecyltrimethylammonium. To accelerate the absorption of the composition through the skin, permeation accelerators such as dimethisulfoxide or tauroglycolic acid can be added to the composition. Hydrogel forming agents which may be used include gelatin and cellulose derivatives such as methylcellulose, hydroxypropylcellulose and hydroxyethylcellulose, as well as synthetic polymers such as polyvinylalcohol. The nature and amount of the hydrogel-forming agents used or the mixtures thereof will depend on the particular viscosity required. The additives that may be present also include moisture retaining substances such as glycerol, sorbitol, 1,2-propylene glycol, butylene glycol and polyols.

USES OF THE COMPOSITIONS It has been shown that the improved composition of the invention is effective to treat epidermal irritations and infections and their symptoms. Accordingly, the present invention also provides a method for treating an epidermal irritation or infection comprising administering an effective amount of a composition comprising stannous fluoride and at least one compound containing zinc to an animal in need thereof. The zinc-containing compound is preferably zinc gluconate and may optionally include zinc chloride. The term "effective amount" means providing an amount at dosages and for periods of time that are effective to achieve the desired result. The frequency of application of the composition of the invention can vary anywhere from one to six times a day, or as needed for the healing process. The course of therapy typically varies from one to six times a day, for seven days, and may be continued as long as it is required for complete relief. The term "animal" as used herein includes all members of the animal kingdom. Preferably, the animal is a mammal such as a human, horse, dog or cat. The term "epidermal irritation" means .. ^ J .. t. ^ ». . . ,. "-. -. _. x,., - -. -.,. , .... .. ... .. z. . . and .z .... z.,. ? S L. ÍZ. any condition that adversely affects or irritates the skin or coat of an animal that includes, but is not limited to, insect bites, flies, burns, psoriasis, dermatitis, acne, and epidermal infections such as subcutaneous mycosis (sporotrichosis, phicomycosis, phacohypomycosis); Cutaneous Habronemiasis; Cutaneous onchocerciasis (Onchocerca cervicalis); Seborrhea; Dermatophilosis (Dermatophilus congolensis); Dermatophytosis (Trichophyton equinum, Trichophyton mentagrophytes, Trichophyton verrucosum); larva of the arble fly (Hypoderma ssp); or larva of the Bot fly (Gasterophilus nasalis / Gasterophilus hemorradalis). The term "infection" means any infection that includes, but is not limited to, infections viral, bacterial, fungal, and parasites, which affect animals. Viral infections that can be treated using the composition of the invention include such herpes viruses • as Herpes Simplex I which causes cold sores and Herpes Zoster which causes rashes; Epstein-Barr virus; Papilloma virus which causes warts; cytomegaurovirus; hepatitis virus; varicella-zoster virus which causes chickenpox; cold and flu viruses; human and feline leukemia virus; human immunodeficiency virus (HIV) and viruses that cause tub.

Bacterial infections that can be treated using the composition of the invention include skin infections by Streptococcus, Staphlococcus and Dermatophilus as well as mycoplasmas related to sinusoidal infections. chronicles. Fungal infections that can be treated using the composition of the invention include yeast infections for the oral cavity and vagina; fungal infections of the finger and toe nails (athlete's foot); and fungal infections of the epidermis of the horse and cow that • include infections caused by the genera Microsporum and Trichophyton. The composition of the invention is particularly well suited for the treatment of epidermal infections such as skin infections as well as eye or eye infections. The invention has shown that the composition is effective in treating many infections in human patients as well as in other mammals that include • horses, cats and dogs. The present invention also provides a use of a composition comprising stannous fluoride and at least one zinc-containing compound for treating an epidermal irritation or infection. The invention further provides a use of a composition comprising stannous fluoride and at least one compound containing zinc to prepare a eimae ^ i? iM ^ medication to treat an epidermal irritation or infection. The following non-limiting examples are illustrative of the present invention: EXAMPLES Example 1 A composition of the present invention comprising stannous fluoride (0.2%) and zinc gluconate (1.5%) was compared to a composition containing stannous fluoride 10 (0.4 %) in the ability to treat cold sores caused by herpes viruses. A placebo containing only glycerin was also prepared. Each composition was tested in 10 patients. The results, shown in Table 1, demonstrate that the average healing time for group 15 that received stannous fluoride with zinc gluconate was 4.2 days compared to 5.9 days for the group that received stannous fluoride alone. This is a significant reduction in the healing time. In addition, the composition that contains • Zinc gluconate contained half the amount of stannous fluoride as compared to the stannous fluoride composition alone. Accordingly, the composition of the present invention provides a much more effective composition as evidenced by the reduced cure time and reduced amount of stannous fluoride required. 25 , rvá? t? m », m .i '- í- i ^ irdtíi'-,. "- *. . *, .. < . ^. ^ ..,. ....- .-, .., .... ,,. TO ..".,.._.. . -,,. "- - - '- - ^ ^ - - ^ - mt Example 2 Five horses infected with the bacterium, Dermatophilus congolensis (commonly known as rain scald) were cured when several applications 5 of a gel with 0.2% stannous fluoride /1.5% zinc gluconate was applied over a period of two weeks. EXAMPLE 3 Five horses infected with fungi of the genus Microphorum and Trichophyton received immediate relief and were cured of infection within a week when treated with a gel containing 0.2% stannous fluoride / 1.5% zinc gluconate. EXAMPLE 4 Five ponies suffering from warts (virus 15 papilloma) on the muzzle, were successfully cured of the disease by applying a gel with 0.2% stannous fluoride / 1.5% zinc gluconate to the affected area several times a day for two weeks. There was no healing. • Example 5 20 Several equines were successfully treated for the dermatitis model (fatty streak, scratches, mud fever) the cause of an infection by staphylococcus / streptococcus / Dermatophilus with bandaged and local applications of a gel with 0.2% fluoride 25 stannous /1.5% zinc gluconate. kfidfiHtfMÉM | aHia | aiÉB > j? .i. x..z .X, .. ^ to. ^ ......

Example 6 Several cats were treated to control tub and oral facial sores of viral etiology with a gel with 0.2% stannous fluoride / 1.5% zinc gluconate. Example 7 Several dogs with bacterial infections of the skin, the result of intense scratching due to insect bites, were successfully treated with several applications of a gel with 0.2% stannous fluoride / 1.5% zinc gluconate. EXAMPLE 8 One patient, burned with candle wax that resulted in a burned area of six inches in diameter, used two applications of a gel with 0.2% stannous fluoride / 1.5% 15 zinc gluconate daily. As a result, the patient did not require the use of pain medication and antibiotics for the infection. The composition not only eased the ^^ severe pain but also prevented the formation of bladders and infection. The area healed completely in less than three weeks with minimal healing. Example 9 A patient burned in an electric heating loop of an oven did not form bladders after immediate application of a gel with 0.2% stannous fluoride / 1.5% zinc gluconate. The patient did not form ^^^ ¿^ j ^ j ^^. - Z ...? Z Í 1 MMfafc. scab and the area did not get infected. EXAMPLE 10 Other skin conditions successfully treated with various applications of a gel with 0.2% stannous fluoride / 1.5% zinc gluconate, include acne, infected insect stings, warts, tub and psoriasis, it seems that the antimicrobial effect of the stannous fluoride and the immunostimulatory properties of zinc gluconate increase synergistically the healing of infections microbials Example 11 Treatment of Herpes. A composition of the present invention comprising 0.2% stannous fluoride; 0.2% zinc chloride and 1.5 of zinc gluconate and the remaining glycerin was compared with a 0.4% composition of stannous fluoride in glycerin in the treatment of herpes virus implex I (cold sores). The study consisted of two groups of 10 healthy adults with cold sores. A group was treated with the composition containing the zinc compounds and the second group with the composition of stannous fluoride alone. The adults treated with the composition containing the zinc compounds had an average healing time of 3.1 days while the group treated with the fluoride only had an average healing time of 3.9 tm t B? - days. As a result, the group treated with the composition of the invention which contained half the amount of stannous fluoride according to the other composition, cured at a faster speed. This study illustrates that the composition of the invention treats herpes infections with much greater efficiency than a composition containing stannous fluoride alone. Example 12 Treatment of Herpes 10 The composition of Example 11 was used to treat several patients who have a herpes rash. Patients reported pain relief and rapid healing when treated with the composition of the invention. In addition, when compared to a composition containing Fluoride stannous alone, patients reported less burn with the composition of the invention. Example 13 Treatment of Bacterial Infections • A patient was treated with the composition of Example 11 for impetigo which is an infection of the skin by streptococcus. The treatment was successful. Another patient used a gel formulation of the present invention to control a resistant skin infection with staphococcus. 25 -ir pfrtÜliWfflir go »- '- - • r"? • i - ft • • -, nrtfcm ». -i r t -ni - »^ ^ - '^^ ~ - Example 14 Cold and Flu Treatment The composition of Example 11 was successfully used to treat ulcers of the throat associated with colds and flu. Example 15 Treatment of Mycoplasma Infection The composition of Example 11 was used to successfully treat mycoplasmas related to a chronic sinusoidal infection Example 16 Treatment of Fungal Infections Fungal infections associated with human fingernails and toenails (athlete's foot), and epidermis of horse 15 and cow as well as fungal infections of the oral cavity and vagina were treated successfully with the composition of Example 11. Example 17 Treatment of Cat Oral Ulcers 20 Oral cat ulcers of viral origin and rickets resulted in healing fast when the composition of Example 11 was applied several times. Example 18 Treatment of Horses 25 The composition of Example 11 has been used for ^ Mi ~ im iíj¡¡i ^ riß UlÉÉfi ^ É Ufarit? H treat many exhibition horses for tub, papilloma virus, warts on the nose and parasitic irritations that include mites and fly bites. All the treatments were successful. Example 19 Treatment of Bovine The composition of Example 11 has been used to treat bovine skin conditions. Example 20 A Preparation of the Compositions of the Invention To prepare the compositions of the invention all pharmaceutical media are heated to 65.55 ° C (150 ° F) and percolated with nitrogen gas to displace the oxygen and remove the water so that the The stannous ion is free from oxidation and hydrolysis during the process of mixing stannous fluoride with zinc compounds. Suitable pharmaceutically acceptable carriers that can be used separately or in combination include glycerin, water, ethanol, polyethylene glycol, polypropylene glycol, and the like. The following provides specific formulations that are within the scope of the present invention. Component Percent by weight Fluoride stannous 0.20 Gluconate zinc 1.50 Glycerin 98.30 ^ ^ ^ ^ ^^^^^^ Component Percent by weight Fluoride stannous 0.20 Zinc gluconate 2.50 Zinc chloride 0.50 Glycerin 96.80 Component Percent by weight Stannous fluoride 0.20 Zinc acetate 2.50 Zinc chloride 0.50 Glycerin 96.80 Component Percent by weight Fluoride stannous 0.20 Zinc gluconate 2.80 Zinc chloride 0.50 L-lysine 15.50 Glycerin 75.00 Carbopol 6.00 Component Percent by weight • Stannous Fluoride 0.25 Zinc Gluconate 1.50 Zinc Chloride 0.50 Glycerin 92.50 Carbopol 3.00 Component Percent by weight Stannous Fluoride 0. twenty Zinc Propionate 2.50 Zinc Chloride 0.50 Glycerin 96.80 Component Weight percent Stale Fluoride 0.20 Zinc Propionate 2.50 Zinc Chloride 0.50 Glycerin 97.30 Component Percent by weight Stannous Fluoride 0.25 Zinc Gluconate 2.25 Zinc Chloride 0.50 Hydroxymethyl Cellulose 30.25 Glycerin 65.50 Carbopol 3.25 While the present invention has been described with reference to what are currently considered to be preferred examples, it should be understood that the invention is not limited to the described examples. On the contrary, the invention is intended to cover various modifications and equivalent measures included within the spirit and scope of the appended claims. All publications, patents and patent applications are incorporated herein for reference and their whole to the same degree as if each publication, patent or individual patent application was specifically and individually indicated to be incorporated for reference in its entirety. TABLE 1 •

Claims

CLAIMS 1. A composition characterized in that it comprises stannous fluoride and zinc gluconate.
2. The composition according to claim 1, further characterized in that it comprises an additional salt of zinc.
3. The composition according to claim 2, characterized in that the zinc salt is selected from the group consisting of zinc chloride, zinc sulfate, zinc phosphate, zinc oxide, zinc pyrophosphate, and zinc thiocyanate.
4. The composition according to claim 2, characterized in that the additional salt of zinc is zinc chloride.
5. The composition according to claim 1, characterized in that it comprises stannous fluoride and zinc gluconate in a non-aqueous medium.
6. Composition in accordance with • claim 1, further characterized in that it comprises additionally at least one amino acid. The composition according to claim 6, characterized in that the amino acid is an essential or non-essential L or D amino acid selected from the group consisting of lysine, arginine, histidine, phenylalanine, threonine, leucine, isoleucine, cysteine, methionine, valina, ___________________________ í ______ ^ l z, i, 4 ..? t StA l. í -i and *. *,, z- X -xzz and, ... ..-. . -. . « . i. Y . ty. z- - ~ l.xz. z xx. - - .y - x,. A 55 > fc- Í > é
7. JMfato; alanine, glycine, proline, glutamine, serine, tryptophan, tyrosine and asparagine.
8. The composition according to claim 1, characterized in that the stannous fluoride 5 is present in an amount from about 0.01% to about 10.0% by weight.
9. The composition according to claim 1, characterized in that the zinc gluconate is present in an amount of about 0.05% up to 10 about 10.0% by weight.
The composition according to claim 2, characterized in that the additional zinc salt is in an amount from about 0.05% to about 10.0% by weight.
11. The composition according to claim 6, characterized in that the amino acid is present in an amount of from about 0.05% to about 50% by weight.
12. The composition according to claim 6, characterized in that the amino acid is L-lysine.
The composition according to claim 1, characterized in that it comprises: Stannous Fluoride 0.20% by weight; Zinc gluconate 1.50% by weight; Y i = * ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡ t ~, H? - 3¡ xyxxí,? nzr- - x-, ^ fa ».. > 'A? I,. «* > . j J > al .1 Glycerin 98.30% by weight. 1 .
The composition according to claim 2, characterized in that it comprises: Stannous fluoride 0.20% by weight; Zinc gluconate 7.50% by weight; Zinc chloride 0.50% by weight; Glycerin 85.50% by weight; and Carbopol 7.30% by weight.
15. The composition according to claim 2, characterized in that it comprises: • Stannous fluoride 0.20% by weight; Zinc gluconate 1.50% by weight; Zinc chloride 0.50% by weight; L-lysine 10.00% by weight; Glycerin 60.00% by weight; Carbopol 2.00% by weight; and Distilled water 24.80% by weight.
16. A method for treating an irritation or epidermal infection, characterized in that it comprises administering an effective amount of a composition comprising stannous fluoride and at least one compound containing zinc to an animal in need thereof.
17. The method according to claim 16, characterized in that the infection is a viral, bacterial, parasitic or fungal infection. ^^^^ * A ^ ¡ja = »¿^ ^ j¿5A ^ -S - ^ __ | a_l ^ afcj = ¿; __ | a ^^ ^ _j > _ _ z. zt? iy.- -ity, jz t lí-z ^ afc »Jia £ A;
18. The method according to claim 17, characterized in that the viral infection is a herpes infection.
19. The method according to claim 5 17, characterized in that the viral infection is an infection of the papilloma virus.
The method according to claim 17, characterized in that the fungal infection is caused by Microsporum or Trichophyton. 10
21. The method of compliance with the claim 17, characterized in that the bacterial infection is a bacterial infection by Staphilococcus, Streptococcus or Dermatophilus.
22. The method according to claim 15, characterized in that the epidermal irritation is a burn.
23. The method according to claim 17, characterized in that the animal is a human.
24. The method according to claim 20 17, characterized in that the animal is a horse, cat or dog.
25. The method according to claim 16, characterized in that the zinc-containing compound is a zinc carboxylate.
26. The method of compliance with the claim 25, characterized in that the zinc carboxylate is selected from the group consisting of zinc gluconate, zinc tartrate, malate zinc, zinc citrate, and zinc acetate.
27. The method according to claim 5, characterized in that the zinc carboxylate is zinc gluconate.
28. The method according to claim 27, characterized in that the composition additionally comprises an additional zinc salt.
29. The method according to claim 28, characterized in that the additional zinc salt is selected from the group consisting of zinc chloride, zinc sulfate, zinc phosphate, zinc oxide, zinc pyrophosphate, and zinc thiocyanate. .
30. The method according to claim 28, characterized in that the additional salt of zinc is zinc chloride.
31. The method of compliance with the claim • 16, characterized in that the composition comprises fluoride 20 stannous and zinc gluconate in a non-aqueous medium.
32. The method according to claim 16, characterized in that the composition additionally comprises at least one amino acid.
33. The method according to claim 25, characterized in that the amino acid is an essential or non-essential L or D amino acid selected from the group consisting of lysine, arginine, histidine, phenylalanine, threonine, leucine, isoleucine, cysteine, methionine, valine, alanine, glycine, proline, glutamine, serine, tryptophan, tyrosine and 5 asparagine.
34. The method according to claim 16, characterized in that the stannous fluoride is present in an amount ranging from about 0.01% to about 10.0% by weight. 10
35. The method according to the claim 27, characterized in that the zinc gluconate is present in an amount ranging from about 0.05% to about 10.0% by weight.
36. The method according to claim 15 28, characterized in that the additional zinc salt is present in an amount ranging from about 0.05% to about 10.0% by weight.
37. The method according to claim w? 32, characterized in that the amino acid is present in a 20 amount from about 0.05% to about 50.0% by weight.
38. The method according to claim 32, characterized in that the amino acid is L-lysine.
39. The method according to claim 25 27, characterized in that the composition comprises: 0.20% by weight stannous fluoride; Zinc gluconate 1.50% by weight; and Glycerin 98.30% by weight.
40. The method according to claim 28, characterized in that the composition comprises: Stannous Fluoride 0.20% by weight; Zinc gluconate 1.50% by weight; Zinc chloride 0.50% by weight; Glycerin 85.50% by weight; and Carbopol 7.30% by weight.
41. The method according to claim 28, characterized in that the composition comprises: Stannous Fluoride 0.20% by weight; Zinc gluconate 1.50% by weight; Zinc chloride 0.50% by weight; L-lysine 10.04% by weight; Glycerin 60.00% by weight; Carbopol 2.00% by weight; and Distilled water 24.80% by weight. iMBT-Tl '* - ffÜJfrf? r • - > . .,,. . ^^. . fc ^ i