Composition for treating a skin disease in an animal

Abstract

The present invention relates to the technical field of veterinary drugs, and more particularly, to a composition for treating 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 containing water and glycerin in which the main active ingredients are soluble. The composition possesses significant curative effects on fungal infections on the skin surfaces of animals, with low toxicity and low irritation.

Description

TECHNICAL FIELD

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

[0002] Although people's lives have improved, in recent years people have experienced increased work pressure and an accelerated pace of life. Therefore, more and more pets, such as dogs and cats, are being adopted into people's homes as companions. As the most common clinical diseases in dogs and cats, skin diseases account for about 20% of clinical cases. Although the prognosis of skin diseases is usually not fatal, skin diseases are difficult to cure, with a high relapse rate and long pathogenesis, and some cases are even incurable. Skin diseases in small animals not only seriously affect their normal life and health, but can also infect humans, and therefore, it is crucial to prevent and treat skin diseases in dogs and cats.

[0003] Canine skin diseases refer to all conditions that can cause pruritus, alopecia, crusts, and abnormal skin lesions in dogs. These lesions have a high recurrence rate and a long pathogenesis, making them difficult to classify and diagnose. Canine skin diseases vary greatly due to factors such as etiology, breed, age, individual differences, dietary composition, living environment, and stress. Formulations, administration time, inappropriate administration routes, and secondary infections all make canine skin diseases more difficult to treat. Fungal skin diseases in dogs are the most common skin diseases in small animals. Although the rate of fungal infection in dogs is relatively high, fungal skin diseases in dogs are generally not fatal, so they have received insufficient attention in the past. With the improvement of human life, the number of pets (dogs and cats) is increasing rapidly.Fungal skin diseases are also becoming common zoonoses that threaten the health and life of animals and humans, so they are receiving increasing attention from people.

[0004] Fungal skin diseases in dogs are the most common skin diseases in small animals. Although the incidence of fungal infections in dogs is relatively high, fungal skin diseases in dogs are generally not fatal, so they have received insufficient attention in the past. With the improvement of human life, the number of pets (dogs and cats) is increasing rapidly. Fungal skin diseases are also becoming common zoonoses, threatening the health and life of animals and humans, and are therefore receiving increasing attention.

[0005] Currently, commonly used antifungal drugs mainly contain azoles, polyenes, allylamines, and nucleic acid inhibitors. Drug resistance and adverse drug reactions have become two significant challenges in the treatment of fungal infections. To reduce drug resistance, drug dosage, and adverse drug reactions, combination therapy is an important treatment 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 treating a skin disease in an animal, the main active ingredients of which are rapamycin, miconazole and meloxicam in a mass ratio of (0.01-10):(0.1-20):(0.1-5), and a mixed solvent containing water and glycerin in which the main active ingredients are soluble.

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

[0008] In some embodiments, a 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 further contains one or more of a pH regulator, an antiseptic, an antisettling agent, a buffer, an osmotic pressure regulator, an antioxidant, a surfactant, and a transdermal penetrant.

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

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

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

[0013] When the said medicament is a casting agent, an excipient contains one or more of 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 boric acid and its salt, phosphoric acid and its salt, acetic acid and its salt, and citric acid and its salt.

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

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

[0017] In some embodiments, the principal active ingredients comprise 0.5% to 5% (e.g., 1%, 2%, 3%, or 4% by weight) of the solvent.

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

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

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

[0021] Reference will be made in detail to embodiments of the present invention, and one or more examples will be described below. Each example is provided to illustrate, rather than limit, the present invention. Indeed, one skilled in the art can obviously make various modifications and changes to the present invention without departing from the scope or spirit of the present invention. For example, features illustrated or described as part of one embodiment may be used in another embodiment to create yet another embodiment.

[0022] Unless otherwise specified, all terms used to disclose the present invention (including technical and scientific terms) have the same meanings as commonly understood by one of ordinary skill in the art to which the present invention belongs. For further guidance, the following definitions are used to better understand the teachings of the present invention. The terms used herein in describing the present invention are for the sole purpose of describing particular embodiments and are not intended to limit the present invention.

[0023] The terms "comprise", "include" and "contain" as used in the present invention are synonymous and are inclusive or open-ended and do not exclude additional unnamed parts, elements or method steps.

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

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

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

[0027] In the present invention, "preferred", "better", "preferably" and "suitable" are intended to describe only embodiments or examples with better effects, and are not to be construed as a limitation on the scope of the present invention.

[0028] Embodiments of the present invention will be described in detail below with reference to examples. It should be understood that these examples are used only to illustrate the present invention and are not intended to limit the scope of the present invention. In the following examples, for a test method for which no specific conditions are specified, it is preferable to refer to the guidance provided in the present invention, a test manual or conditions customary in the art, another test method known in the art, or conditions recommended by a manufacturer.

[0029] In the following specific examples, a measurement parameter related to an ingredient may exhibit a slight deviation within one weighing accuracy, unless otherwise noted. For temperature and time parameters, an acceptable deviation is permitted due to equipment testing accuracy or operator accuracy. Example 1

[0030] The present invention provides a composition for treating a skin disease in an animal, wherein a dosage form of the composition is a dropper, and a solvent is a mixture of water and glycerin in a ratio of 7:3. The composition contains 3% by weight of active ingredients, and the active ingredients are rapamycin, miconazole, and meloxicam in a mass ratio of 5:10:3.

[0031] A 10 mL solution obtained from the above mixture was heated to 45°C, 0.05 g of poloxamer and 0.5 g of sucrose were added and mixed uniformly, and phosphate was used as a buffer to adjust the pH to 7.5. The resulting solution was transferred to a dropper bottle. Example 2

[0032] The present invention provides a composition for treating a skin disease in an animal, wherein a dosage form of the composition is a dropper, and a solvent is a mixture of water and glycerin in a ratio of 7:3. The composition contains 1% by weight of active ingredients, and the active ingredients are rapamycin, miconazole, and meloxicam in a mass ratio of 1:10:5.

[0033] A 10 mL solution obtained from the above mixture was heated to 40°C, 0.05 g of poloxamer and 0.5 g of sucrose were added and mixed uniformly, and phosphate was used as a buffer to adjust the pH to 6.0. The resulting solution was transferred to a dropper bottle. Example 3

[0034] The present invention provides a composition for treating a skin disease in an animal, wherein a dosage form of the composition is a dropper, and a solvent is a mixture of water and glycerin in a ratio of 7:3. The composition contains 0.5% to 5% by weight of active ingredients, and the active ingredients are rapamycin, miconazole, and meloxicam in a mass ratio of 10:1:1.

[0035] A 10 mL solution obtained from the above mixture was heated to 50°C, 0.05 g of poloxamer and 0.5 g of sucrose were added and mixed uniformly, and phosphate was used as a buffer to adjust the pH to 8.5. The resulting solution was transferred to a dropper bottle. Test example

[0036] The following test was conducted to demonstrate the preventive and therapeutic effects of the composition mentioned in Example 1 on canine skin diseases. Twelve dogs from a local breed were used in the test and divided into two groups of six dogs each. The twelve dogs included six males and six females, with an average body weight of 7.80 kg. The twelve dogs had an average age of 1.5 years and no history of dermatophytosis. The twelve dogs were fed quantitative amounts of commercially available food, had free access to water, and were regularly immunized. The strain was Microsporum canis, which was isolated by the researchers.

[0037] With reference to the procedure 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 for cats was established at a concentration of 10 5 Spores / mL were used for infection. The vaccinated animals were injected intramuscularly with sedatives and placed on their sides. Their backs were shaved. Inoculation sites were marked on the dorsal skin. Four squares with sides of approximately 35 mm were drawn on both sides of the dorsum (dorsal side from the 6th to the 7th rib) and the loin (two sides from the 3rd to the 4th lumbar vertebrae). Spores were inoculated onto a designated region using a glass rod.

[0038] Appetite, water intake, and body condition were observed daily. Body weight, rectal temperature, inoculation sites, total hair growth, and lesion sizes (diameter) were checked weekly using a Wood's lamp. Erythema, hardness, scales, or crusts were recorded. Based on infection, routine blood tests (red blood cell count, white blood cell count, hematocrit, hemoglobin content, and red blood cell index) were performed biweekly. After inoculation, the chest and abdominal walls were brushed 20 times a week with a toothbrush, including the inoculation sites. The toothbrush was then placed on DTM medium for inoculation. The DTM medium was cultured at 25°C for 3 weeks, and microscopic examination confirmed that infections with Microsporum canis had been successfully induced.

[0039] The test lasted 28 days, and the drug in Example 1 was administered percutaneously to the dogs. In the Example 1 group, an applicator was used to drip the drug onto the dorsal skin of the animals once daily at a dose of 0.1 mL per kilogram of body weight. The control group received no drug.

[0040] After treatment, on days 1, 7, 14, and 28, tissue was taken from the dogs' epidermis for fungal culture, and the strains were cultured on DTM and SDA medium and identified. See the table below for Microsporum canis culture (a number represents the number of Microsporum canis in the delimited region).

[0041] From the above table, it can be seen that the fungal infections were significantly alleviated after 7 days of continuous administration of the drug provided by the present invention, and basically no obvious symptoms were observed on day 14. Referring to animal observations (scratching, rubbing, skin condition, etc. in dogs), it was found that the drug provided by the present invention could substantially cure fungal infections within 7 days.

[0042] Only a few examples of the present invention are described in the above-mentioned embodiments. These explanations are relatively detailed and specific, but should not be construed as limiting the scope of the present invention. It should be noted that a person of ordinary skill in the art could make various modifications and improvements without departing from the concept of the present invention. These modifications and improvements are all within the scope of the present invention. QUOTES CONTAINED IN THE DESCRIPTION

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

[0000] Deboer D, Moriello K., Vet. Microbiol, 1994, 42(56):289-295

[0037]

Claims

[1] A composition for treating a skin disease in an animal, the main active ingredients of which are rapamycin, miconazole and meloxicam in a mass ratio of (0.01 - 10):(0.1 - 20):(0.1 - 5), and a mixed solvent comprising water and glycerol in which the main active ingredients are soluble. [2] A composition for treating a skin disease in an animal according to claim 1, wherein a mass ratio of rapamycin, miconazole and meloxicam is (0.1-8):(1-15):(0.5-3). [3] A composition for treating a skin disease in an animal according to claim 2, wherein a mass ratio of rapamycin, miconazole and meloxicam is (1-5):(5-10):(1-3). [4] A composition for treating a skin disease in an animal according to any one of claims 1 to 3, which further comprises one or more of a pH regulator, an antiseptic, an antisettling agent, a buffer, an osmotic pressure regulator, an antioxidant, a surfactant and a transdermal penetrant. [5] A composition for treating a skin disease in an animal according to claim 4, wherein the buffer is selected from one or more of boric acid and its salt, phosphoric acid and its salt, acetic acid and its salt, and citric acid and its salt. [6] A composition for treating a skin disease in an animal according to claim 4, wherein the anti-settling agent is sucrose. [7] A composition for treating a skin disease in an animal according to any one of claims 1, 3, 5 and 6, wherein the composition is a dripping agent or a pouring agent.