WO2015110800A1

WO2015110800A1 - Herbal composition and its use for modifying animal behavior

Info

Publication number: WO2015110800A1
Application number: PCT/GB2015/050109
Authority: WO
Inventors: Louise Reynolds; Deborah MCGEOWN
Original assignee: Norbrook Laboratories Limited
Priority date: 2014-01-21
Filing date: 2015-01-19
Publication date: 2015-07-30
Also published as: GB2522271A; GB2522271B; GB201400988D0

Abstract

The present invention relates to an herbal composition and its use for modifying animal behavior. The invention also refers to the administration of said herbal composition by spraying or air diffusion to non-human mammals, including cats and dogs, for modifying their behavior.

Description

Herbal Composition and Its Use for Modifying Animal Behavior

Technical Field

This invention relates generally to the field of animal behavior and, more particularly, to an herbal composition and its use for the treatment or prevention of stress, or for inducing a friendly behavior, in non-human mammals. The invention also refers to the administration of the herbal composition by spraying or air diffusion.

Background Art

The use of herbs and herbal extracts for treating various human and animal diseases is well established. See Kessler D, et al, The Doctor's Complete Guide to Healing Medicines (Berkley Health Reference Books, Berkeley, California, US, 1996). Herbal medications are available in many forms, including capsules, tablets, pellets, tinctures, powders, fresh or dried plants or plant parts, teas, juices, creams and ointments, essential oils, or as combinations of any of these forms. Herbal medicines are administered by any one of various methods, including orally, parenterally, enterally, transdermally, intravenously, via feeding tubes and topically.

Several patents have been issued for innovative herbal compositions useful in human and veterinary medicine. For instance, herbal compositions which include Glycyrrhiza uralensis, Sigesbeckia orientalis and Impatiens balsamina, in combination with other plants, have been shown to have anti-inflammatory characteristics. See Wu W, CNl 102993, Tani M, EP0654271, Whittle B, GB2254783 and Hu S, US5627195. Recent research has also shown that certain herbal extracts and their combinations have appeasing and anti-anxiety properties in humans and animals. See Ott D, et al, US20030012824.

A critical issue pertaining to the use of herbal therapy in veterinary medicine is getting an animal to digest or stay in the close proximity of the herbal composition. The oral administration of medicines has some serious shortcomings as animals are reluctant to chew tablets or ingest pills. In addition, the combination of the therapeutic agent with the animal's food may not be effective. Although liquid drops can be placed on its food, there is a risk that the animal may not eat the food in which the herbs have been absorbed. Even worse, the liquid may never be ingested because it drips to the bottom of the dispenser or the food in which the drops are absorbed becomes unpalatable to the animal. In view of this situation, the use of sprays and diffusers has been proposed as a suitable mean of administering these medicaments to animals.

Summary of the Invention

In a first aspect, the present invention relates to a composition comprising valerian (Valeriana officinalis), impatiens spp (Impatiens glandulifera, Impatiens balsamina) and wild clematis (Clematis aristata), their oils, extracts, derivatives or synthetic equivalents thereof. The composition of the invention is effective in reducing anxiety and inducing a friendly behavior in non-human mammals. Compared to other known veterinary anxiolytic compounds, the composition of the invention does not have any negative consequences.

In a second aspect, the present invention refers to a composition according to the first aspect for its use as a medicament.

In a third aspect, the present invention is directed to a composition according to the first aspect for its use in the treatment or prevention of stress, or for inducing a friendly behavior, in a non-human mammal. Alternatively, the present invention is directed to the use of the composition according to the first aspect in the manufacture of a medicament for the treatment or prevention of stress, or for inducing a friendly behavior, in a non-human mammal.

In a fourth aspect, the present invention refers to a method for treating or preventing stress, or for inducing a friendly behavior, in a non-human mammal, which comprises administering to the non-human mammal a therapeutically effective amount of the composition of the first aspect.

Description of the Embodiments

This invention relates to a novel herbal composition comprising valerian (Valeriana officinalis), impatiens (Impatiens glandulifera, Impatiens balsamina) and wild clematis (Clematis aristata), their oils, extracts, derivatives or synthetic equivalents thereof. The composition shows an unquestionable relaxing effect in non-human mammals. In addition, the general behavior and friendliness of non-human mammals are significantly improved when the composition of the invention is applied. The composition is administered by spraying or air diffusion.

1. Definitions

The term "extract" as used herein relates to the product of extracting a plant material for a sufficient period of time (typically 1 -48 hours) with a suitable solvent, typically an organic solvent, carbon dioxide and water, or mixtures of such solvents with each other. Solvents frequently preferred are aqueous mixtures of lower alkaloids (i.e. containing from 1 to 4 carbon atoms). Typical extraction temperatures are in the range of from about 0°C to about 100°C. Elevated pressures may be applied, but extraction at ambient pressure is frequently preferred. Generally, suitable extracts may be liquid or dry and may be obtained, generally, by removing the solvent from the primary product of extraction.

The term "friendly behavior" as used herein, means: i) reducing or eliminating the barking, growling, trembling, nervousness or reluctance to be approached in a suject, or ii) stimulating or promoting the willingness to approach, sniffing or tailing in a subject, when the subject is in the presence of another individual or group of individuals, especially human individuals.

The terms "prevent", "preventing" and "prevention" as used herein, refer to inhibiting the inception, or decreasing the occurrence or recurrence, of a disease or condition in a subject. Prevention may be complete (e.g. the total absence of pathological cells in a subject) or partial. Prevention also refers to a reduced susceptibility to a clinical condition.

The term "subject" as used herein, refers to a non-human mammal, such as non- human primate (e.g. chimpanzees and other apes and monkey species), a farm animal (e.g. cattle, sheep, pigs, goats and horses), a domestic mammal (e.g. dogs and cats), or a laboratory animal (e.g. rodents, such as mice, rats and guinea pigs). The term does not denote any particular age or sex. The term "therapeutically effective amount" as used herein, refers to any amount of a composition which, when administered to a subject: i) prevents the inception or recurrence or ii) causes the reduction or remission of the disease or condition against which the composition is effective.

The term "treat" or "treatment" as used herein, refers to the control of the progression of a disease or condition after its clinical signs have appeared. Control of the disease or condition progression is understood to mean the beneficial or desired clinical results that include, but are not limited to, reduction of the symptoms, reduction of the duration of the disease, stabilization of pathological states (specifically to avoid additional deterioration), delaying the progression of the disease, improving the pathological state, and remission (both partial and total). The control of progression of the disease or condition also involves an extension of survival, compared with the expected survival if treatment is not applied.

2. Composition of the invention

In a first aspect, the present invention relates to a composition comprising valerian {Valeriana officinalis), impatiens spp (Impatiens glandulifera, Impatiens balsamina) and wild clematis {Clematis aristata), their oils, extracts, derivatives or synthetic equivalents thereof. Preferably, oils, extracts, derivatives or synthetic equivalents of valerian, impatiens spp and wild clematis are employed.

In one embodiment, the composition of the invention further comprises a C2-C8 alcohol (e.g. ethanol, propanol, isopropanol, butanol, pentanol, hexanol, heptanol, octanol, phenyl ethyl alcohol) or a combination thereof. Preferably, the alcohol is a C2-C5 alcohol. More preferably, the alcohol used is ethanol.

In another embodiment, the composition of the invention further comprises a lipophilic organic diluent. The organic diluent can be derived from an alkylene oxide, such as ethylene oxide or propylene oxide. Preferably, the diluent employed is ethylene glycol, propylene glycol, dipropylene glycol, dipropylene glycol monoethyl ether, dipropylene glycol methyl or a combination thereof. More preferably, the diluent is propylene glycol.

In a further embodiment, the composition of the invention comprises valerian from about 0.0625% to about 0.250% w/v, impatiens spp from about 0.15% to about 0.6% w/v, wild clematis from about 0.15% to about 0.6% w/v, a C₂-C₈ alcohol or phenyl ethyl alcohol from about 0.5% to about 97% w/v, and a lipophilic organic diluent from about 2.5% to about 99% w/v, based on the total volume of the composition. Preferably, the composition of the invention comprises valerian from about 0.125% w/v, impatiens spp from about 0.3% w/v, wild clematis from about 0.3% w/v, a C₂-C₈ alcohol or phenyl ethyl alcohol from about 0.5% to about 96% w/v, and propylene glycol is from about 2.5% to about 98% w/v, based on the total volume of the composition. Preferably, the alcohol and the lipophilic organic diluent used are ethanol and propylene glycol, respectively.

In another embodiment, the composition of the invention consists of valerian (i.e. Valeriana officinalis), impatiens spp (i.e. Impatiens glandulifera, Impatiens balsamina), wild clematis (i.e. Clematis aristata), their oils, extracts or derivatives thereof, ethanol and propylene glycol.

The composition of the invention may comprise optionally a coloring (e.g. food yellow no. 5, food red no. 3, food blue no. 2, food lake dye, titanium dioxide, red iron oxide, yellow iron oxide), a flavoring (e.g. caramel, carrot, apple, cinnamon oil) agent or a fragrance. Preferably, the coloring, flavoring or fragrance content of the composition is from about 0.25% to about 1% w/v, and more preferably, from about 0.5% w/v, based on the total volume of the composition.

Extracts of valerian, impatiens spp and wild clematis suitable for use according to the present are obtainable commercially and are defined in various pharmacopoeias. The extracts of the medicinal plants mentioned herein may be used in liquid or solid form, or in admixture with each other, as well as compounded with other additives and adjuvants used in the making of medical preparations (e.g. diluents, binders, disintegrants, lubricants, anti- adherents, flow promotors. Typical examples of such additives include maltodextrin, microcrystalline cellulose, soya-derived polysaccharides, polyethylene glycol (e.g. Macrogol), magnesium stearate and colloidal anhydrous silica.

3. Use of the composition of the invention in veterinary medicine

In a second, third and fourth aspects, the present invention refers to several ways and methods of applying the composition of the invention in veterinary medicine. Preferably, the composition of the invention is used in the treatment or prevention of stress, or for inducing a friendly behavior, in non-human mammals. Alternatively, the composition of the invention may be used in the manufacture of a medicament for the treatment or prevention of stress, or for inducing a friendly behavior, in non-human mammals. The invention also refers to a method for treating or preventing stress, or inducing a friendly behavior, in a non-human mammal, which comprises administering to the non-human mammal a therapeutically effective amount of the composition of the invention. Preferably, the non-human mammal is a domestic pet. More preferably, the domestic pet is a cat or a dog.

The composition of the invention can be administered in a number of different ways depending on the targeted non-human mammal. For instance, the composition can be applied directly to the coat or skin of a mammal, or sprayed on surfaces or objects in the mammal's environment, or diffused or sprayed into the air in the mammal's environment. The composition can also be sprayed on floors, walls or animal toys about once a week, or once or several times daily. In addition, the composition can be delivered by a diffuser, such as a plug-in or battery diffuser, set appropriately to attain the desired behavioral modification. Alternatively, diffuser strips impregnated with the composition may be employed. There are many commercially available diffusers suitable for administering the composition of the invention. The composition can also be incorporated to a plasticized material, such as PVC, to make a tag or a collar.

This invention is further illustrated by the following examples which should not be construed as limiting. The contents of all documents cited throughout this application are incorporated herein in their entirety by reference.

Example 1

Comparative analysis of the effects of D-PET-010, Pet Remedy and Adaptil in dogs

A test group of eight dogs aged approximately 4-7 years old was used. All animals were confirmed as clinically healthy prior to their inclusion in the assay. The subjects were kept in designated premises at a housing unit. The temperature within the unit was maintained at 17°C to 24°C. The animals were fed with TEKLAD® Certified Global 21% Protein Dog Diet, antibiotic free (Harlan Laboratories, Inc., Indianapolis, Indiana, US). Water was available ad libitum. 1. Pre-exposure phase

During the pre-exposure phase of the study, the test animals were observed during seven days for two different parameters: barking and body posture. A score value was given to these observations according to Table 1.

Table 1

The animals were observed twice daily for approximately 30 minutes.

In addition, a "friendly stranger" response test was added to the study to evaluate the reaction of the animal to the approach of a "friendly" unknown individual. The test was conducted on three occasions during the pre-exposure phase. See Tod E, et al, App. Animal Behav. Sci. 2005; 93:295-308. People not associated with everyday contact with the test animals were used for this purpose. The test incorporated the person adopting a kneeling position, face to face with the dog with their arm extended and their palm facing upwards whilst encouraging the dog to come forward. A scoring system that included a recording for negative (X), normal (0) and positive (V) behavior was applied to each test. An example of negative behavior includes barking, growling, trembling, nervousness or reluctance to approach when prompted. Examples of positive behavior include willingness to approach, sniffing or tailing.

2. Post-exposure phase

During the post exposure phase, the test animals were exposed to the following products: 1) D-PET-010, a solution including valerian oil 0.125% (w/v), impatiens HDL 0.3%, wild clematis 0.3%, propylene glycol 10% (w/v) and ethanol 89.275% (w/v), from days 0 to 6.

2) PET REMEDY® Plug-in Diffuser ("Pet Remedy", Unex Designs Ltd., Torqay, UK), from days 9 to 13.

3) ADAPTIL® Diffuser ("Adaptil", Ceva Animal Health Ltd., Amersham, UK), from days 16 to 20.

The D-PET-010 composition was administered by means of a battery operated diffusing unit. The Pet Remedy and Adaptil compositions were administered by using plug- in diffusers. Batteries and compositions were replenished when necessary.

The animals were observed twice daily for approximately 30 minutes to assess their vocalization and body posture. The "friendly stranger" test was conducted on three separate occasions. Table 2 illustrates the results obtained during the post-exposure phase of the study.

Table 2

In summary, the dogs exposed to D-PET-010 experienced a significant reduction in barking and developed a more friendly behavior towards unknown human beings than when treated with Pet Remedy and Adaptil. Moreover, D-PET-010 did not induce any negative responses in the test subjects. D-PET-010 was also effective in reducing over 80% the stress level in dogs.

Example 2

Comparative analysis of the effects of D-PET-010, Pet Remedy and F elm ay in cats A test group of 12 cats aged approximately 2-8 years old was used. All animals were confirmed as clinically healthy prior to their inclusion in the assay. The subjects were kept in designated premises at a housing unit. The temperature within the unit was maintained at 17°C to 26°C. The animals were fed with TEKLAD® Global Cat Diet, antibiotic free (Harlan Laboratories, Inc., Indianapolis, Indiana, US). Water was available ad libitum.

1. Pre-exposure phase

During the pre-exposure phase of the study, the test animals were observed during five days for two different parameters: aggression and body posture. A score value was given to these observations according to Table 3.

Table 3

The animals were observed daily. In addition, a "friendly stranger" test was conducted on three occasions during the pre-exposure phase. See Tod E, 2005, supra.

2. Post-exposure phase

During the post-exposure phase, the test animals were exposed to the following products:

1) D-PET-010, from days 0 to 4.

2) Pet Remedy, from days 10 to 14.

3) FELIWAY® Diffuser ("Feliway", Ceva Animal Health Ltd., Amersham, UK), from days 26 to 28. The D-PET-0101 composition was administered by means of a battery operated diffusing unit. The Pet Remedy and Feliway compositions were administered using plug-in diffusers. Batteries and compositions were replenished when necessary.

The animals were observed daily for assessing their aggression and body posture. The "friendly stranger" test was conducted on three separate occasions. Table 4 illustrates the results obtained during the post-exposure phase of the study.

Table 4

The cats exposed to D-PET-010 developed a more friendly behavior towards unknown human beings than when treated with Pet Remedy and Feliway. More importantly, D-PET-010 did not induce any significant negative responses in the test subjects, while Pet Remedy and Feliway elicited unfriendly behavior in 19% and 13% of the cases, respectively. In addition, D-PET-010 was also effective in reducing the aggression and stress levels in cats 77% and 73%, respectively.

Claims

1. A composition comprising valerian, impatiens spp and wild clematis, their oils, extracts, derivatives or synthetic equivalents thereof.

2. The composition according to claim 1, further comprising a C₂-C₈ alcohol or phenyl ethyl alcohol.

3. The composition according to any preceding claim, further comprising a lipophilic organic diluent.

4. The composition according to any preceding claim, wherein valerian is from about 0.0625% to about 0.250% w/v, impatiens spp is from about 0.15% to 0.6% about w/v, wild clematis is from about 0.15% to about 0.6% w/v, the C₂-C₈ alcohol or phenyl ethyl alcohol is from about 0.5% to about 97% w/v, and the lipophilic organic diluent is from about 2.5% to about 99% w/v, based on the total volume of the composition.

5. The composition according to any preceding claim, wherein valerian is from about 0.125% w/v, impatiens spp is from about 0.3% w/v, wild clematis is from about 0.3% w/v, the C₂-C₈ alcohol or phenyl ethyl alcohol is from about 0.5% to about 96% w/v, and propylene glycol is from about 2.5% to about 98% w/v based on the total volume of the composition.

6. The composition according to any preceding claim, wherein the C₂-C₈ alcohol is ethanol.

7. The composition according to any preceding claim, wherein the lipophilic organic diluent is propylene glycol.

8. The composition according to any one of claims 1 to 7 for use as a medicament.

9. The composition according to any one of claims 1 to 7 for use in the treatment or prevention of stress, or for inducing a friendly behavior, in a non-human subject.

10. Use of the composition according to any one of claims 1 to 7 in the manufacture of a medicament for the treatment or prevention of stress, or for inducing a friendly behavior, in a non-human subject.

11. A method for treating or preventing stress, or for inducing a friendly behavior, in a non-human subject, which comprises administering to the non-human subject a therapeutically effective amount of the composition according to any one of claims 1 to 7.

12. The method of claim 11 wherein the composition is administered by a spray or a diffuser.

13. The method of claim 12 wherein the diffuser is a plug-in or battery diffuser.

14. The method of claim 11 wherein the non-human subject is a cat or a dog.

15. A composition consisting of valerian, impatiens spp, wild clematis their oils, extracts or derivatives thereof, ethanol and propylene glycol.