COMPOSITION FOR THE TREATMENT OF SKIN DISEASES IN ANIMALS

Abstract

The present invention relates to the technical field of veterinary drugs, in particular 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 of water and glycerin in which the main active ingredients are soluble. The composition has a significant curative effect on fungal infections on the skin surfaces of animals, with low toxicity and low irritation.

Description

TECHNICAL FIELDThe present invention relates to the field of veterinary medicine and more particularly to a composition for treating a skin disease in an animal.BACKGROUNDIn recent years, although human life has improved, working pressure and life pace have increased. Therefore, more and more animals such as dogs and cats are being ingested as domestic shoots. Skin diseases are the most common clinical diseases in dogs and cats and account for about 20% of clinical cases. Although prognosis of skin diseases is not usually fatal, skin diseases are difficult to heal, have a high relapse rate and a long course of disease, and some cases are even un healable. Skin diseases in small animals not only impair their normal life and health, but can also infect humans.Skin diseases in dogs refer to any diseases which can cause pruriticism, alopecia, crusts and abnormal skin lesions in dogs which have a high rebound rate and a long pathogenesis and are difficult to categorize and diagnose. Skin diseases in dogs are very different due to factors such as etiology, breed, age, individual differences, feed composition, environment of life and stress. Formulations, time of administration, improper routes of administration or secondary infections make it difficult to treat skin diseases in dogs. Fungal skin diseases in dogs are the most common skin diseases in small animals. Although the fungal infection rate in dogs is relatively high, fungal skin diseases in dogs are not usually fatal and have therefore not been sufficiently observed in the past. As people improve their habitat, the number of domestic animals (dogs and cats) increases rapidly. Fungal skin diseases become common zoons that threaten the health and life of animals and humans and are therefore increasingly being observed by humans.Fungal skin diseases in dogs are the most common skin diseases in small animals. Although the fungal infection rate in dogs is relatively high, fungal skin diseases in dogs are not usually fatal, so they have not been sufficiently observed in the past. As people improve their habitat, the number of domestic animals (dogs and cats) increases rapidly. Fungal skin diseases become common zoons that threaten the health and life of animals and humans and are therefore increasingly being observed by humans.Currently common antifungal agents include, in particular, azoles, polyenes, allylamines and nucleic acid inhibitors. In the treatment of fungal infections, drug resistance and adverse drug effects have become two major challenges. In order to reduce drug resistance, drug dosage and adverse drug effects, the combination of drugs is an important treatment method for fungal infections. At present, there are various antifungal agents for topical application, most of which, however, are ineffective or require long term administration.SUMMARYThe present invention relates to a composition for treating a skin disease in an animal, the principal 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 of water and glycerol in which the principal active ingredients are soluble.In some embodiments, the mass ratio of rapamycin, miconazole, and meloxicam is (0.1-8):(1-15):(0.5-3).In some embodiments, the mass ratio of rapamycin, miconazole, and meloxicam is (1-5):(5-10):(1-3).In some embodiments, the composition for treating skin disease in an animal further comprises one or more pH regulators, an antiseptic, an anti-settling agent, a buffer, an osmotic pressure regulator, an antioxidant, a surfactant, and a transdermal penetration agent.The pH regulator is used to adjust the pH of the drug to be close to or equal to the pH of the pet's skin. The proportion of the pH regulator is between 0.01 % and 5 % and is adjusted depending on the type of specific drug. The pH regulator comprises one or more of citric acid, hydrochloric acid, phosphoric acid, benzoic acid, sodium hydroxide and potassium hydroxide. The proportions of the pH regulator are, for example, 0.01 %, 0.1%, 0.5%, 1%, 2%, 3%, 4% and 5%.The proportion of the antioxidant ranges from 0.01 % to 5 %, and the antioxidant can prevent or retard the oxidation and improve the stability of the drug. The antioxidant comprises one or more of tocopherol, butylated hydroxy anisole, dibutyl hydroxy toluene, and tert-butyl hydroquinone. The proportions of the antioxidant are, for example, 0.01 %, 0.05 %, 0.1 %, 0.2 %, 0.3 %, 0.4 %, 0.5 %, 1 %, 2 %, 3 %, 4 % and 5 %.The transdermal penetration agent is one or more of propylene glycol, laurocapram, caprylic / capric triglycerides and diethylene glycol monoethyl ether. Propylene glycol can be used as both a solvent and a transdermal penetrating agent and has good effects for use in pharmaceutical preparations, and therefore propylene glycol is the preferred transdermal penetrating agent. The proportion of the transdermal penetration agent ranges from 0.1% to 5%. The proportion of the transdermal penetration agent is, for example, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4% and 5%.When the aforementioned drug is a casting agent, an excipient comprises one or more of the following: the solvent, the transdermal penetration agent, a co-solvent, and the antioxidant.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.In some embodiments, the anti-settling agent is sucrose.In some embodiments, the composition for treating skin disease in an animal is a drop or a casting agent.In some embodiments, the principal actives constitute from 0.5% to 5% (e.g., 1%, 2%, 3%, or 4%) by weight of the solvent.In some embodiments, the pH of the composition for treating a skin disease in an animal is in the range of 6.0 to 8.5.In some embodiments, the composition is used for treating a skin disease in an animal for treating a fungal skin disease in a cat or dog.The composition has a significant curative effect on fungal infections on animal skin surfaces, with low toxicity and low irritation.DESCRIPTION OF THE EMBODIMENTSReference 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 and not limit the present invention. Indeed, various modifications and changes can be made to the present invention by those skilled in the art 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 provide another embodiment.Unless otherwise stated, all terms (including technical and scientific terms) used to disclose the present invention have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains. For a better understanding of instructions of the present invention, the following definitions are used. The terms used herein in the description of the present invention are used only to describe specific embodiments and are not intended to limit the present invention.The terms "comprising", "including" and "containing" used in the present invention are synonymous and do not exclude additional, non-mentioned members, elements or method steps.A range of values in the present invention defined by endpoints includes all values, fractions and said endpoints that fall within the range.In the present invention, descriptions such as "plural" and "different" refer to two or more than two unless otherwise specified.In the present invention, the technical features in the open-ended descriptions include both closed technical solutions including the listed features and open technical solutions including the listed features.In the present invention, "preferable", "better", "advantageous" and "suitable" are intended only for describing embodiments or examples with better effect and should not be understood as limiting the scope of the present invention.The embodiments of the present invention will be described in detail below by way of 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, a test method for which a certain condition is not specified is preferably determined according to the instructions in the present invention, a test manual or a conventional condition known in the art, another test method known in the art, or a condition recommended by a manufacturer.In the following specific examples, a measurement parameter related to an ingredient may have a slight deviation within a weighing accuracy range unless otherwise specified. For temperature and time parameters, an acceptable deviation is allowed due to the test accuracy of the instrument or the operating accuracy.Example 1The present invention provides a composition for treating a skin disorder in an animal, wherein a dosage form of the composition is a drop agent and a solvent is a mixture of water and glycerol in a ratio of 7:3. The composition contains 3 wt% of active ingredients, and the active ingredients are rapamycin, miconazole, and meloxicam in a mass ratio of 5:10:3.10 The resulting solution of the above mixture was heated to 45°C, 0.05 g poloxamer and 0.5 g sucrose were added and mixed uniformly, and phosphate was used as a buffer to adjust the pH to 7.5. The resulting solution was placed in a dropping bottle.Example 2The present invention provides a composition for treating a skin disorder in an animal, wherein a dosage form of the composition is a drop agent and a solvent is a mixture of water and glycerol 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 1:10:5.10 The resulting solution of the above mixture was heated to 40°C, 0.05 g poloxamer and 0.5 g sucrose were added and mixed uniformly, and phosphate was used as a buffer to adjust the pH to 6.0. The resulting solution was placed in a dropping bottle.Example 3The present invention provides a composition for treating a skin disorder in an animal, wherein a dosage form of the composition is a drop agent and a solvent is a mixture of water and glycerol in a ratio of 7:3. The composition contains 0.5 wt % to 5 wt % of active ingredients, and the active ingredients are rapamycin, miconazole, and meloxicam in a mass ratio of 10:1:1.10 The resulting solution of the above mixture was heated to 50°C, 0.05 g poloxamer and 0.5 g sucrose were added and mixed uniformly, and phosphate was used as a buffer to adjust the pH to 8.5. The resulting solution was placed in a dropping bottle.Test ExampleThe following test was conducted to detect the prevention and treatment effects of the above-mentioned composition of Example 1 in skin diseases of dogs. Twelve dogs of the local breed were used for the test and divided into 2 groups with 6 dogs in each group. The twelve dogs included 6 breeds and 6 mouths 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 were fed commercial feed, allowed free access to water and were routinely vaccinated. The strain is Microsporum canis,which has been separated by researchers.With reference 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. The vaccinated animals were injected intramuscularly with sedatives and placed on the side, their back was shaved, the inoculation sites on the dorsal skin were marked, and 4 squares with a side length of about 35 mm were drawn on both sides of the back (dorsal side of the 6 th to 7 th costa) and the lobe (two sides of the 3 rd to 4 th lumbar vertebrae). The spores were inoculated with a glass rod into a certain region.Appetite, water absorption and body condition were observed daily. Body weight, rectal temperature, inoculation sites, total wool growth and size of the lesions (diameter) were examined weekly with the Woods lamp. Redness, hardening, scale or crusts were recorded. Due to infections, routine studies of blood were performed two weeks (number of red and white blood cells, hematocrit, hemoglobin content and red blood cell index). After inoculation, the breast and abdominal walls were brushed with a toothbrush 20 times a week 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 successful artificial induction of Microsporum canis was confirmed by microscopic examination.The duration of the test was 28 days and the drug of Example 1 was percutaneously administered to the dogs. In the group of Example 1, the drug was dropped onto the back skin of the animals once daily with an applicator at a dose of 0.1 ml per kilogram of body weight. No drug was administered to the control group.After treatment, on days 1, 7, 14 and 28, tissues were taken from the epidermis of the dogs for fungal culture, and the strains were cultured and identified on DTM and SDA medium. The following table lists the cultures of Microsporum canis(a number stands for the number of Microsporum canisin the delimited region). It is evident from the above table that after 7 days of continuous administration of the medicament according to the invention, the fungal infections were significantly alleviated and no evident symptoms were in principle observed on day 14. With respect to the observations of the animals (scratching, rubbing, skin conditions, etc. in dogs), it was found that the pharmaceutical composition according to the invention could basically heal fungal infections within 7 days.In the above embodiments, only some examples of the present invention will be described. The descriptions are relatively detailed and specific, but may not be construed as limiting the scope of the present invention. It should be understood 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 are all within the scope of the present invention.References included in the specificationThis list of documents cited by the applicant has been produced in an automated manner and is only included for the better information of the reader. The list is not part of the German patent application or utility model application. The DPMA does not take any adhesion for any faults or omissions.Cited Non-Patent LiteratureDevelopment of an Experimental Model of Microsporum Canis Infection in Cats (Deboer D, Moriello K., Vet Microbiol, 1994, 42(56):289-295

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Claims

A composition for treating a skin disorder in an animal, the principal 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 of water and glycerin in which the principal active ingredients are soluble.The composition for treating 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).The composition for treating 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).The composition for treating skin disease in an animal according to any one of claims 1 to 3, further comprising one or more pH regulators, an antiseptic, an anti-settling agent, a buffer, an osmotic pressure regulator, an antioxidant, a surfactant, and a transdermal penetration agent.The composition for treating a skin disorder 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.The composition for treating a skin disorder in an animal according to claim 4, wherein the anti-settling agent is sucrose.A composition for treating skin disease in an animal according to any one of claims 1, 3, 5 and 6, wherein the composition is a drop agent or a pour agent.