阅读说明：本技术 组合物及其用于治疗慢性猫呼吸系统疾病的用途 (Composition and application thereof for treating chronic feline respiratory disease ) 是由 A·贝克 E·霍奇金斯 M·拉宾 V·提尼斯 于 2018-03-01 设计创作，主要内容包括：本发明涉及可用于兽药领域的组合物,更具体地涉及包含信息素的组合物,其用于治疗猫慢性呼吸系统疾病及其并发症和/或猫慢性感染性疾病或病症。(The present invention relates to compositions useful in the field of veterinary medicine, more particularly to compositions comprising pheromones for use in the treatment of feline chronic respiratory disease and its complications and/or feline chronic infectious disease or disorder.)

1. A veterinary composition comprising a pheromone for use in the treatment of chronic infectious disease in a cat.

2. A veterinary composition comprising a pheromone for use in the treatment of chronic respiratory disease, more particularly upper respiratory disease, in cats.

3. The composition according to claim 1 or 2, wherein the feline chronic infectious disease or feline chronic respiratory disease is due to an infection, such as a herpes infection, including FHV-1 infection.

4. A veterinary composition comprising a pheromone for use in the treatment of clinical symptoms of chronic respiratory disease in cats and/or the prevention of recurrence or relapse thereof due to infection, more particularly due to herpes infection, including FHV-1 infection.

5. A veterinary composition comprising a pheromone for use in the treatment of chronic upper respiratory disease in cats.

6. The composition of claim 5, wherein the treatment reduces or reduces sneezing.

7. A veterinary composition comprising a pheromone for the treatment of sneezing in cats, more particularly sneezing associated with infection.

8. A veterinary composition comprising a pheromone for increasing relaxation as evidenced by increased sleep time in cats with an infectious disease and/or a respiratory disease.

9. Use of a veterinary composition comprising a pheromone for reducing clinical symptoms caused by chronic infections in cats, such as herpes infections, including FHV-1 infections.

10. The use according to claim 9, wherein the clinical symptom caused by chronic infection in cats is coughing, sneezing, nasal discharge, nasal congestion, eye secretions, ocular congestion and/or blepharospasm, preferably sneezing.

11. Use of a veterinary composition comprising a pheromone for reducing the clinical symptoms of chronic respiratory disease, especially chronic upper respiratory disease in cats, caused by infection, for example herpes infection, including FHV-1 infection.

12. Use according to claim 11, wherein the clinical symptoms of chronic respiratory disease in cats following infection are coughing, sneezing, nasal discharge and/or nasal obstruction, preferably sneezing.

13. Use of a composition according to any one of claims 1 to 8 or a composition according to any one of claims 9 to 12, wherein the veterinary composition comprises a mixture of oleic, azelaic, pimelic and palmitic acids or derivatives thereof.

14. Use of a composition according to any one of claims 1 to 8 or a composition according to any one of claims 9 to 12, wherein the composition comprises at least a therapeutically effective amount of an active fatty acid or derivative thereof, including ester or methyl ester derivatives thereof, more particularly selected from oleic, azelaic, pimelic and palmitic acids or derivatives thereof.

15. Use of a composition according to any one of claims 1 to 8 or a composition according to any one of claims 9 to 12, wherein the composition comprises: a mixture of fatty acids comprising at least about 45-60% oleic acid, 6-10% azelaic acid, 8-12% pimelic acid and 13-18% palmitic acid, relative to the total weight of the fatty acids and derivatives thereof; or a mixture comprising about 45-65% methyl oleate, about 6-10% dimethyl azelate, about 8-12% dimethyl pimelate, and about 13-18% methyl palmitate, relative to the total weight of fatty acids and derivatives thereof; or a mixture of fatty acid esters comprising about 47-51% methyl oleate, about 7-9% dimethyl azelate, 9-11% dimethyl pimelate and about 14-16% methyl palmitate, relative to the total weight of fatty acids and derivatives thereof.

Technical Field

The present invention relates to compositions useful in the field of veterinary medicine, more particularly to compositions comprising pheromones for use in the treatment of feline chronic respiratory disease and its complications and/or feline chronic infectious disease or disorder.

Background

Feline infectious diseases are common. The main cause of feline infectious diseases is believed to be the virus that infects the feline respiratory tract, and virally infected cats mostly exhibit symptoms similar to common cold, such as upper respiratory tract inflammation, coughing, sneezing, conjunctivitis, rhinorrhea, nasal discharge, watery mouth, fever, pneumonia, stomatitis, glossitis, granularization, tongue ulcer, nasal ulcer, systemic skin ulcer, turbinate ulcer, diarrhea, vomiting, anorexia, and reduced vitality. More specifically, cats are more likely to show the above symptoms when they are infected with feline herpes virus.

Feline herpesvirus 1(FHV-1) is the most common feline infectious disease among cats, with over 90% of cats housed in a community setting being infected. This organism is associated with a severe morbidity during the acute phase of infection (upper respiratory disease, conjunctivitis and keratitis), and many infected cats present chronic and recurrent clinical symptoms of the disease.

Feline herpesvirus 1(FHV-1) is believed to be the most common feline infectious disease in cats; the infection may be subclinical, or it may lead to clinical symptoms of the disease, including sneezing, coughing, conjunctivitis, fever, keratitis, dyspnea, loss of appetite, lethargy, occasional pneumonia, and death. Morbidity and mortality in crowded or stressful environments such as refuges can be high. Upper respiratory tract disorders include sneezing, coughing, and/or conjunctivitis.

After acute exposure, most cats develop persistent infections in which the trigeminal ganglion is the major site of viral latency. With the recurrence of clinical symptoms and increased FHV-1 dissemination (shedding), a latent reactivation of FHV-1 can occur. It is believed that the stress event causes the reactivation of FHV-1 within the first few weeks. In one study, the mean time to signs of Upper Respiratory Infection (URI) was 8.3 days, and cats with the highest stress score in the first week in refuges were more likely to develop URIs (Tanaka A, Wagner DC, Kass PH, et al.

At present, there is no significant treatment for feline viral diseases and feline respiratory diseases, and in fact these diseases can only be treated symptomatically, such as nutritional treatment, administering nutritional feeds to the cats to be treated to relieve and restore their physical vitality and/or dehydration symptoms, and administering antibiotics to them to prevent multiple or secondary infections, and physically removing viscous secretions.

Thus, there is a need to develop new therapies for the treatment of chronic respiratory disease and its complications in cats and/or infectious diseases or conditions in cats, particularly sneezing cats associated with infection.

Pheromone therapy ("pheromonatopherapy" or "pheromonotherpy") is a method of managing behavioral problems in non-human mammals by using chemicals with pheromone properties. It is an innovative treatment of stress-related problems in non-human mammals, including domestic animals, particularly cats and dogs, as well as non-companion animals. Pheromone therapy has been most extensively studied in dogs and cats.

Pheromones are chemical substances used for communication between individuals of the same species. Some chemicals that provide inter-species communication are called allelochemicals (allelochemicals). Some compounds are known to be pheromones in one species, but behavioral effects have been observed in other species. Pheromones will be used herein in a broad sense, i.e. any naturally or non-naturally occurring (synthetic) compound which has a behavioral effect on a non-human mammal. The exact mechanism of action of most pheromones is not clear, but they cause some alterations in the limbic system and hypothalamus.

Pheromone therapy is a good way to manage the welfare of non-human mammals, especially some common stress-related behavioral disorders in domestic mammals such as dogs and cats.

It has been found that compositions of pheromones can reduce the clinical symptoms of chronic respiratory disease in cats caused by infection. More specifically, it has been shown herein that exposure to pheromones reduces the sneezing associated with FHV-1 and increases relaxation during sleep. The same combination of pheromones can help prevent recurrence or recurrence of these respiratory diseases.

Disclosure of Invention

Accordingly, the present invention relates to a veterinary composition comprising a pheromone for use in the treatment of a chronic feline respiratory disease or a complication thereof and/or a feline chronic infectious disease or disorder.

The invention also relates to a method for treating chronic respiratory disease or complications thereof in cats and/or chronic infectious disease or complications thereof in cats comprising administering a veterinary composition comprising a pheromone to a cat in need thereof.

The invention also relates to the use of a veterinary composition of pheromones for the preparation of a medicament for the treatment of chronic respiratory diseases or complications thereof in cats and/or chronic infectious diseases or disorders in cats.

The invention also relates to the use of a veterinary composition comprising a pheromone for alleviating clinical symptoms caused by chronic infections (e.g. herpes infections, including FHV-1 infections) in cats. The invention also relates to the use of a veterinary composition comprising a pheromone for alleviating the clinical symptoms of chronic respiratory disease in cats, particularly chronic upper respiratory disease in cats, caused by infection, such as herpes infection, including FHV-1 infection.

Drawings

FIG. 1: study timetable

FIG. 2: the proportion of sneezing at the observation point for the different groups and times.

Indicates the statistical differences between groups.

Detailed Description

In a particular embodiment, the invention relates to a veterinary composition comprising a pheromone for use in the treatment of a feline respiratory disease, more particularly chronic upper respiratory disease. More specifically, chronic respiratory disease in cats is caused by infection (e.g., herpes infection, including FHV-1 infection). More particularly, the invention provides a veterinary composition comprising a pheromone, which is particularly useful for treating sneezing in cats associated with infections (e.g., herpes infections, including FHV-1 infections).

In a more specific embodiment, the invention relates to a veterinary composition comprising a pheromone for use in treating clinical symptoms (e.g. sneezing) and/or preventing the recurrence or recurrence of chronic respiratory disease in cats that is caused by infection, more particularly by herpes infection, including FHV-1 infection.

In another embodiment, the invention relates to a veterinary composition comprising a pheromone for use in treating clinical symptoms (e.g. sneezing) and/or preventing the recurrence or recurrence of chronic respiratory disease in cats that is caused by infection, more particularly by herpes infection, including FHV-1 infection.

Another object of the invention is the use of a veterinary composition comprising a pheromone for alleviating clinical symptoms due to chronic infections (e.g. herpes infections, including FHV-1 infections) in cats.

Another object of the invention is the use of a veterinary composition comprising a pheromone for alleviating the clinical symptoms of chronic respiratory disease in cats, particularly chronic upper respiratory disease in cats, caused by infection, such as herpes infection, including FHV-1 infection.

The clinical symptoms of chronic respiratory disease in cats usually caused by FHV-1 infection are more specifically upper respiratory tract inflammation, coughing, sneezing, conjunctivitis, rhinorrhea, nasal discharge or nasal obstruction. It may also evolve into watery mouth, eye secretions, blepharospasm, fever, asthma, pneumonia, stomatitis, gastrointestinal disorders such as irritable bowel syndrome, glossitis, granular adenitis, tongue ulcers, nasal ulcers, systemic skin ulcers, turbinate ulcers, diarrhea, vomiting, anorexia and/or hypomotility. Chronic upper respiratory disease in cats is usually inflammation of the upper respiratory tract, coughing, sneezing, conjunctivitis, rhinorrhea, nasal discharge, nasal obstruction, or a mixture thereof.

In a particular embodiment, the clinical symptom of chronic respiratory disease in cats following infection is coughing, sneezing, nasal discharge and/or nasal obstruction, and preferably sneezing.

Clinical symptoms of chronic infectious diseases in cats are usually infections of the feline respiratory tract and thus include upper respiratory inflammation, coughing, sneezing, conjunctivitis, rhinorrhea, or nasal obstruction. Symptoms may also include watery mouth, ocular secretions, ocular congestion, blepharospasm, fever, asthma, pneumonia, stomatitis, gastrointestinal disorders such as irritable bowel syndrome, glossitis, granular adenitis, tongue ulcers, nasal ulcers, systemic skin ulcers, turbinates ulcers, diarrhea, vomiting, anorexia, and/or hypomotility.

In a particular embodiment, the clinical symptom caused by chronic infection in cats is cough, sneezing, nasal discharge, nasal congestion, eye secretions, ocular congestion, and/or blepharospasm, and preferably sneezing.

Recurrence or recurrence of feline respiratory disease caused by infection (more specifically due to FHV-1) occurs frequently, which is why the disease is considered chronic. The recurrence or recurrence of these feline respiratory diseases, particularly sneezing caused by infection, appears to be due to a lack of vitality, lack of relaxation, lack of immune defenses, and/or lack of sleep. It has been found herein that such recurrence or relapse can be prevented or reduced by administering a composition comprising a pheromone, particularly by increasing relaxation during sleep in cats.

In another embodiment, the invention relates to a veterinary composition comprising a pheromone for use in treating clinical symptoms and/or preventing the recurrence or recurrence of chronic respiratory disease in cats that is caused by infection, more particularly by herpes infection, including FHV-1 infection.

More preferably, the chronic upper respiratory illness in cats is typically upper respiratory inflammation, coughing, sneezing, conjunctivitis, rhinorrhea, nasal discharge, nasal obstruction, or a mixture thereof.

In another embodiment, the invention relates to a veterinary composition comprising a pheromone for use in treating a feline upper respiratory disease. More specifically, chronic respiratory disease in cats is caused by infection (e.g., herpes infection, including FHV-1 infection). According to a particular embodiment, the present invention relates to a veterinary composition comprising a pheromone for the treatment of sneezing, more preferably infection-related sneezing.

In a particular embodiment, the composition according to the invention reduces or reduces sneezing, more particularly sneezing associated with infections (e.g. herpes viruses, including more particularly FHV-1).

In another specific embodiment, the composition according to the invention increases relaxation as evidenced by an increase in sleep time in cats suffering from infectious diseases and/or respiratory diseases.

The present invention relates to compositions or mixtures comprising pheromones. The pheromone is one or more fatty acids and/or esters thereof, or more specifically ethyl or methyl esters thereof, as an active ingredient. Thus, the composition comprises a fraction or mixture of fatty acid esters or fatty acid methyl ester derivatives. They can be administered to cats by diffusion into the surrounding air.

The amount of fatty acid, ester derivative or methyl ester derivative in the composition may vary within wide ranges. They may be present in amounts of about 0.5 to 95%, preferably 1 to 70% or 1; 5 to 50 percent.

According to the invention, "fatty acid" means a hydrocarbon chain with mono-or dicarboxylic acids, which is saturated or unsaturated, linear or branched, active, and capable of inducing behavioral changes in non-human mammals. These fatty acids typically have C4-C22. They are selected from oleic acid, palmitic acid, azelaic acid, pimelic acid, capric acid, myristic acid, palmitoleic acid, linoleic acid, stearic acid, arachidonic acid, n-butyric acid, isobutyric acid, alpha-methylbutyric acid, capric acid, pivalic acid, gamma-linoleic acid, eicosapentaenoic acid, pentadecanoic acid, tridecanoic acid or docosahexaenoic acid.

"derivatives of fatty acids" means all active volatile derivatives of fatty acids. Preferably, the derivatives are in the ester or methyl or ethyl ester form.

The mixture comprises at least one fatty acid, such as oleic acid, a derivative of oleic acid, an ester or methyl ester derivative thereof.

By way of example, we may cite fatty acid mixtures or derivatives thereof, including esters or methyl esters thereof, such as:

a mixture of oleic acid and palmitic acid;

a mixture of oleic acid and n-butyric acid;

a mixture of oleic, palmitic and linoleic acids;

a mixture of oleic, palmitic, linoleic and palmitoleic acids;

mixtures of capric, lauric, myristic, palmitoleic, palmitic, linoleic, and oleic acids;

mixtures of oleic, palmitic, linoleic, myristic acids;

a mixture of oleic, palmitic, linoleic, lauric and myristic acids;

a mixture of oleic acid, palmitic acid, linoleic acid, myristic acid and pentadecanoic acid;

mixtures of oleic, palmitic, linoleic, myristic, pentadecanoic and stearic acids;

a mixture of oleic acid, palmitic acid, linoleic acid, myristic acid, lauric acid and pentadecanoic acid;

mixtures of lauric acid, myristic acid, pentadecanoic acid, palmitic acid, stearic acid, oleic acid, linoleic acid; or more preferably

A mixture of oleic acid, azelaic acid, pimelic acid and palmitic acid.

The compositions of the invention may contain the above-mentioned fatty acids in suitable proportions, as is well known to those skilled in the art. For example, the mixture may contain, relative to the total weight of fatty acids and derivatives thereof:

about 55-65% oleic acid and 45-35% palmitic acid, their derivatives and ester or methyl ester derivatives thereof;

about 45% oleic acid, 16% azelaic acid, 18% pimelic acid and 21% palmitic acid, derivatives thereof, ester or methyl ester derivatives thereof;

about 30% palmitic acid, 30% oleic acid and 40% linoleic acid, their derivatives, their ester and methyl ester derivatives; or

About 30% palmitic acid, 40% linoleic acid, 10% palmitoleic acid, and 20% oleic acid, their derivatives, their ester and methyl ester derivatives.

Percentages are by weight unless otherwise indicated.

As used herein, the term "about" or "approximately" will be understood by one of ordinary skill in the art and will vary to some extent depending on the context in which it is used. If the use of this term is ambiguous to one of ordinary skill in the art based on the context in which it is used, "about" or "approximately" will mean up to plus or minus 10% of the particular term.

According to one embodiment of the invention, the composition comprises at least a therapeutically effective amount of an active fatty acid, its derivatives (including ester or methyl ester derivatives thereof), more particularly selected from oleic acid, azelaic acid, pimelic acid and palmitic acid. The mixture of fatty acids preferably comprises at least about 45-60% oleic acid, 6-10% azelaic acid, 8-12% pimelic acid and 13-18% palmitic acid, relative to the total weight of the fatty acids and derivatives thereof. In the case of the ester and methyl ester forms, the mixture comprises, relative to the total weight of the fatty acids and their derivatives, about 45-65% of methyl oleate, about 6-10% of dimethyl azelate, about 8-12% of dimethyl pimelate and about 13-18% of methyl palmitate. Preferably, the mixture of fatty acid esters comprises about 47-51% methyl oleate, about 7-9% dimethyl azelate, 9-11% dimethyl pimelate and about 14-16% methyl palmitate, relative to the total weight of fatty acids and derivatives thereof.

The composition of the invention comprises a pheromone as described above. The composition may be free of solvents, excipients, plant extracts or even an aqueous phase. Alternatively, the composition may comprise solvents, excipients, plant extracts. They may contain solvents including isoalkanes and cycloalkanes. They are generally present in the form of an oily phase and a liquid phase, depending on the temperature, and can be heated by any suitable means in order to obtain diffusion in air of the fatty acids and their derivatives, their esters or methyl ester derivatives.

Thus, the fatty acid mixture according to the invention can be administered to cats by diffusion in the ambient air. Administration to cats may be with or without heat. The diffusion of the composition in ambient air is continued for 6 to 30 days.

In a specific embodiment, the compositions disclosed herein are in a form for oral, nasal, intradermal, dermal, inhalation, or parenteral administration. Preferably, the composition is in a form for diffusion in ambient air.

In another embodiment, the composition for use in the present invention is in the form of a liquid solution, suspension, solid or semi-solid, powder, pellet, capsule (capsules), granule, dragee, gel (gelule), spray, pill, tablet, paste or gel (gels).

At ambient temperature, the composition may be in liquid form or in solid form, depending on the length and structure of the compounds (in particular the solvent or excipient and the pheromone) contained in the composition of the invention, and therefore the length and structure of the carbon chain of the compounds.

The dispenser for diffusion may be selected by one skilled in the art depending on the form of the composition (solid or liquid). It may be a dispenser such as that described in US design patent US D752,730S.

In a preferred embodiment, administration is accomplished by allowing the cat to inhale a composition of pheromones that can diffuse in the ambient air surrounding the locus of the cat.

Cats include cats and all members of the feline family, domestic cats, and more commonly all cat races. They include domestic, farm or zoo cats, particularly cats of any age, such as kittens.

Another object of the invention is a kit or a delivery device for diffusing a composition of the invention as defined above into a cat, allowing the composition to diffuse in air.

These devices may be, in particular, electronic devices for evaporation or diffusion, comprising a solid support having a ceramic plate and a polymer matrix, on which a sufficient amount of the composition of the invention as defined above can be applied in such a way that diffusion can take place. These means may be in the form of an electrical needle equipped with a compartment consisting of a supporting ceramic plate suitable for heating and on which the platelets impregnated with the fatty acid composition according to the invention may be placed. The device is activated by plugging in a power supply. Part of the composition of the invention diffuses through the opening in the compartment of the platelet under the action of heat. These are comparable to those used for spreading mosquito repellent. The device may also be a dispenser as described in US design patent US D752,730S.

Other aspects and advantages of the invention will be disclosed in the experimental section below.

Examples