Composition for the treatment of skin diseases in animals

Abstract

The present invention relates to the technical field of veterinary medicinal products, in particular a composition for the treatment of a skin disease in an animal. The main active ingredients of the composition are rapamycin, miconazole, and meloxicam in a mass ratio of (0.01–10):(0.1–20):(0.1–5) and a mixed solvent of water and dimethylacetamide in which the main active ingredients are soluble. The composition has a significant curative effect on fungal infections on the skin surface of animals, with low toxicity and minimal irritation.

Description

TECHNICAL AREA

[0001] The present invention relates to the technical field of veterinary medicinal products, in particular a composition for the treatment of a skin disease in an animal. BACKGROUND

[0002] While people's quality of life has improved in recent years, so too have work pressures and the pace of life. As a result, more and more animals, such as dogs and cats, are kept as pets in private homes. Skin diseases are the most common clinical conditions in dogs and cats, accounting for approximately 20% of clinical cases. Although skin diseases are generally not fatal, they are difficult to treat, have a high relapse rate and a long course, and some cases are even incurable. Skin diseases in small animals not only significantly affect their normal lives and health but can also be transmitted to humans. Therefore, the prevention and treatment of skin diseases in dogs and cats is of crucial importance.

[0003] Skin diseases in dogs encompass all conditions that can cause itching, hair loss, crusting, and abnormal skin changes. They have a high relapse rate, a long course, and are difficult to classify and diagnose. Skin diseases in dogs vary greatly due to factors such as etiology, breed, age, individual differences, diet composition, living environment, and stress. The composition of medications, the timing of administration, incorrect routes of administration, or secondary infections further complicate the treatment of skin diseases in dogs. Fungal skin infections are the most common skin diseases in small animals. Although the infection rate in dogs is relatively high, fungal skin infections in dogs are generally not fatal and have therefore historically received insufficient attention.With the improvement in people's living conditions, the number of pets (dogs and cats) is increasing rapidly. Fungal skin infections are also becoming common zoonoses that threaten the health and lives of animals and humans, and are therefore receiving increasing attention.

[0004] Fungal skin infections are the most common skin diseases in dogs. Although the infection rate in dogs is relatively high, fungal skin infections in dogs are usually not fatal and have therefore received insufficient attention in the past. With the improvement of human living conditions, the number of pets (dogs and cats) is increasing rapidly. Fungal skin infections are also becoming common zoonoses that threaten the health and lives of both animals and humans, and are therefore receiving increasing attention.

[0005] Currently, common antifungal drugs mainly comprise azoles, polyenes, allylamines, and nucleic acid inhibitors. Drug resistance and side effects have become two major challenges in the treatment of fungal infections. To reduce drug resistance, dosage, and side effects, drug combination therapy is an important treatment approach for fungal infections. Currently, various topical antifungal drugs are available, but most are ineffective or require long-term administration. SUMMARY

[0006] The present invention relates to a composition for the treatment of a skin disease in an animal, comprising the main active ingredients rapamycin, miconazole and meloxicam in a mass ratio of (0.01 - 10):(0.1 - 20):(0.1 - 5), and a mixed solvent of water and dimethylacetamide in which the main active ingredients are soluble.

[0007] In some embodiments, the mass ratio of rapamycin, miconazole and meloxicam is (0.1 - 8):(1 - 15):(0.5 - 3).

[0008] In some embodiments, the mass ratio of rapamycin, miconazole and meloxicam is (1 - 5):(5 - 10):(1 - 3).

[0009] In some embodiments, the composition for treating a skin disease in an animal additionally comprises one or more pH regulators, antiseptics, an anti-deposition agent, a buffer, an osmotic pressure regulator, an antioxidant, a surfactant and a transdermal penetration agent.

[0010] The pH regulator is used to adjust the pH of the medication so that it is close to or equal to the pH of a pet's skin. The concentration of the pH regulator ranges from 0.01% to 5% and is adjusted depending on the specific medication. The pH regulator contains one or more of the following substances: citric acid, hydrochloric acid, phosphoric acid, benzoic acid, sodium hydroxide, and potassium hydroxide. For example, the concentrations of the pH regulator are 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, and 5%.

[0011] The antioxidant concentration ranges from 0.01% to 5%, and the antioxidant can prevent or delay oxidation and improve the stability of the drug. The antioxidant contains one or more of the following substances: tocopherol, butylhydroxyanisole, dibutylhydroxytoluene, and tert-butylhydroquinone. For example, the antioxidant concentrations are 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, and 5%.

[0012] The transdermal penetration agent is one or more of the following: propylene glycol, laurocapram, caprylic / capric triglyceride, and diethylene glycol monoethyl ether. Propylene glycol can be used both as a solvent and as a transdermal penetration agent and has good efficacy when used in pharmaceutical preparations, which is why propylene glycol is the preferred transdermal penetration agent. The proportion of the transdermal penetration agent ranges from 0.1% to 5%. For example, the proportions of the transdermal penetration agent are 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, and 5%.

[0013] If the above medicinal product is a casting agent, an excipient comprises one or more of the following components: the solvent, the transdermal penetration agent, a co-solvent, and the antioxidant.

[0014] In some embodiments, the buffer is selected from one or more of the following substances: boric acid and its salts, phosphoric acid and its salts, ethanoic acid and its salts, and citric acid and its salts.

[0015] In some embodiments, the anti-deposition agent is sucrose.

[0016] In some embodiments, the composition for treating a skin disease in an animal is a drip or pour-on preparation.

[0017] In some embodiments, the main active ingredients constitute 0.5 wt.% to 5 wt.%, for example 1 wt.%, 2 wt.%, 3 wt.% or 4 wt.%, of the solvent.

[0018] In some embodiments, the pH value of the composition for treating a skin disease in an animal is in the range of 6.0 to 8.5.

[0019] In some embodiments, the composition is used to treat a skin disease in an animal, for example, to treat a fungal skin disease in a cat or dog.

[0020] The composition has significant healing effects on fungal infections on the skin surfaces of animals, with low toxicity and low irritation. DESCRIPTION OF THE EXECUTION FORMS

[0021] Detailed reference is made to embodiments of the present invention, and one or more examples are described below. Each example serves to illustrate the present invention and not to limit it. In fact, a person skilled in the art can make various modifications and changes to the present invention without departing from its scope or spirit. For example, features shown or described as part of one embodiment can be used in another embodiment to create yet another embodiment.

[0022] Unless otherwise stated, all terms used in the disclosure of the present invention (including technical and scientific terms) have the same meaning as they are generally understood by a person skilled in the art in the field of the present invention. For the sake of clarity, the following definitions are used with reference to further information. The terms used in the description of the present invention serve only to describe specific embodiments and are not intended to limit the present invention.

[0023] The terms “comprise”, “contain” and “include” used in the present invention are synonymous and are inclusive or open and do not exclude additional, unmentioned members, elements or process steps.

[0024] A range of values ​​in the present invention, defined by endpoints, includes all values, fractions and the said endpoints that lie within the range.

[0025] In the present invention, descriptions such as "a plurality of" and "different" refer to two or more, unless otherwise specified.

[0026] In the present invention, technical features in open descriptions include closed technical solutions, including the listed features, and also include open technical solutions, including the listed features.

[0027] In the present invention, “preferred”, “better”, “preferably” and “suitable” serve only to describe embodiments or examples with better effects and are not to be understood as limiting the scope of protection of the present invention.

[0028] The embodiments of the present invention are described in detail below with reference to examples. It is understood that these examples serve only to illustrate the present invention and not to limit its scope. In the following examples, for a test procedure for which no specific condition is given, reference is preferably made to the instructions provided in the present invention, a test manual, a conventional condition in the art, another test procedure known in the art, or a condition recommended by the manufacturer.

[0029] In the following specific examples, a measurement parameter relating to an ingredient may vary slightly within a weighing range unless otherwise stated. For temperature and time parameters, an acceptable deviation is permitted due to the accuracy of the measuring instruments or operator accuracy. Example 1

[0030] The present invention relates to a composition for treating a skin disease in an animal, wherein one dosage form of the composition is a dropper and the solvent is a mixture of water and dimethylacetamide in a ratio of 7:3. The composition contains 3% by weight of active ingredients, wherein the active ingredients are rapamycin, miconazole, and meloxicam in a mass ratio of 5:10:3. 10 ml of the resulting solution of the above mixture were heated to 45 °C, 0.05 g of poloxamer and 0.5 g of sucrose were added and mixed thoroughly, and phosphate was used as a buffer to adjust the pH to 7.5. The resulting solution was placed in a dropper bottle. Example 2

[0031] The present invention relates to a composition for treating a skin disease in an animal, wherein one dosage form of the composition is a dropper and the solvent is a mixture of water and dimethylacetamide in a ratio of 7:3. The composition contains 1% by weight of active ingredients, wherein the active ingredients are rapamycin, miconazole, and meloxicam in a mass ratio of 1:10:5. 10 ml of the resulting solution of the above mixture were heated to 40 °C, 0.05 g of poloxamer and 0.5 g of sucrose were added and mixed thoroughly, and phosphate was used as a buffer to adjust the pH to 6.0. The resulting solution was placed in a dropper bottle. Example 3

[0032] The present invention relates to a composition for treating a skin disease in an animal, wherein one dosage form of the composition is a dropper and one solvent is a mixture of water and dimethylacetamide in a ratio of 7:3. The composition contains 0.5 wt% to 5 wt% active ingredients, and the active ingredients are rapamycin, miconazole, and meloxicam in a mass ratio of 10:1:1. 10 ml of the resulting solution of the above mixture were heated to 50 °C, 0.05 g of poloxamer and 0.5 g of sucrose were added and mixed thoroughly, and phosphate was used as a buffer to adjust the pH to 8.5. The resulting solution was placed in a dropper bottle. Test series

[0033] The following tests were conducted to demonstrate the preventive and therapeutic efficacy of the composition described in Example 1 in canine skin diseases. Twelve dogs of a local breed were used for the tests and divided into two groups of six dogs each. The twelve dogs consisted of six males and six females with an average body weight of 7.80 kg. The twelve dogs were on average 1.5 years old and had no history of dermatophytosis. The twelve dogs received quantitative doses of commercially available food, had free access to water, and were routinely vaccinated. The strain is Microsporum canis, which was isolated by the researchers.

[0034] Referring to the method described in “Development of an Experimental Model of Microsporum Canis Infection in Cats” (Deboer D, Moriello K., Vet Microbiol, 1994, 42(56):289-295), the inoculation model of Microsporum canis in cats was used for infection at a concentration of 10 5 Spores / ml were used. The vaccinated animals were given an intramuscular injection of sedatives, placed on their sides, their backs were shaved, the inoculation sites on the dorsal skin were marked, and four squares with sides of approximately 35 mm were drawn on both sides of the back (dorsal from the 6th to the 7th rib) and the lumbar region (bilaterally from the 3rd to the 4th lumbar vertebrae). The spores were injected into a specific location using a glass rod.

[0035] Appetite, water intake, and body condition were observed daily. Body weight, rectal temperature, injection sites, total coat growth, and lesion size (diameter) were examined weekly using a Wood's lamp. Erythema, induration, scaling, or crusting were documented. Based on the infections, blood tests (red blood cell count, white blood cell count, hematocrit, hemoglobin level, and erythrocyte index) were performed every two weeks. After inoculation, the chest and abdominal wall, including the inoculation sites, were brushed 20 times per week with a toothbrush. The toothbrush was then placed on DTM medium for inoculation. The DTM medium was cultured at 25°C for 3 weeks, and infections with Microsporum canis were confirmed as successfully artificially induced by microscopic examination.

[0036] The test duration was 28 days, and the drug from Example 1 above was administered percutaneously to the dogs. In the group from Example 1, the drug was applied once daily to the skin of the animals' backs using an applicator at a dose of 0.1 ml per kilogram of body weight. The control group received no drug.

[0037] Following treatment, tissue samples were taken from the epidermis of the dogs on days 1, 7, 14, and 28 for fungal culture. The strains were cultured on DTM and SDA medium and identified. The Microsporum canis culture is listed in the following table (the numbers indicate the number of Microsporum canis in the delineated area).

[0038] The preceding table shows that after 7 days of continuous administration of the medicament provided in the present invention, the fungal infections were significantly alleviated, and on day 14, essentially no obvious symptoms were observed. Based on observations of the animals (scratching, rubbing, skin conditions, etc. in dogs), it was determined that the medicament provided in the present invention can essentially cure fungal infections within 7 days.

[0039] The preceding embodiments describe only a few examples of the present invention. The descriptions are relatively detailed and specific, but cannot be interpreted as limiting the scope of the present invention. It should be noted that a person skilled in the art could also make several variations and improvements without departing from the concept of the present invention. These variations and improvements all fall within the scope of protection of the present invention. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited non-patent literature

[0000] Development of an Experimental Model of Microsporum Canis Infection in Cats“ (Deboer D, Moriello K., Vet Microbiol, 1994, 42(56):289-295

[0034]

Claims

Composition for the treatment of a skin disease in an animal, comprising the main active ingredients rapamycin, miconazole and meloxicam in a mass ratio of (0.01 - 10):(0.1 - 20):(0.1 - 5), together with a mixed solvent of water and dimethylacetamide in which the main active ingredients are soluble. Composition for the treatment of a skin disease in an animal according to claim 1, wherein the mass ratio of rapamycin, miconazole and meloxicam is (0.1 - 8):(1 - 15):(0.5 - 3). Composition for the treatment of a skin disease in an animal according to claim 2, wherein the mass ratio of rapamycin, miconazole and meloxicam is (1 - 5):(5 - 10):(1 - 3). Composition for the treatment of a skin disease in an animal according to one of claims 1 to 3, further comprising one or more pH regulators, antiseptics, anti-settling agents, buffers, osmotic pressure regulators, antioxidants, surfactants and transdermal penetration agents. Composition for the treatment of a skin disease in an animal according to claim 4, wherein the buffer is selected from one or more of the following: boric acid and its salts, phosphoric acid and its salts, ethanoic acid and its salts, and citric acid and its salts. Composition for the treatment of a skin disease in an animal according to claim 4, wherein the anti-setting agent is sucrose. Composition for the treatment of a skin disease in an animal according to one of claims 1, 3, 5 and 6, wherein the composition is a drop-based or pour-on preparation.