Composition for relieving stress and fear of pets and application thereof

Abstract

The invention discloses a composition for relieving stress and fear of pets and application of the composition, and belongs to the technical field of animal nutritional health-care products, the composition for relieving stress and fear of pets comprises the following raw materials in percentage by weight: 0.1-20% of a relieving component, 1-20% of amino acid, 0.1-10% of an antioxidant and 55-90% of a functionalizing agent, and the sum of the weight percentages of all the raw materials is 100%; the invention further discloses a specific composition and proportion of the relieving component, and the composition for relieving stress and fear of the pets can be used for daily health care to prevent stress of the pets and can also be used before possible stress, such as transportation or before seeing a doctor.

Description

Technical Field

[0001] The invention belongs to the technical field of animal nutrition and health products, and particularly relates to a composition for relieving pet stress and fear and application thereof. Background Art

[0002] In recent years, the pet economy has been developing in full swing, and the number of pet dogs and cats has been rising year by year, with the number of pets exceeding 100 million. At present, the pet-keeping population is mainly urban population. Most of them are restricted by urban management and office workers’ lack of enough time to accompany their pets. Dogs and cats are living alone at home, which seriously limits their opportunities to contact the outside world. It is easy to cause timidity and fear in dogs and cats, causing them to experience stress when going out, seeking medical treatment, or meeting strangers or in unfamiliar environments, which has an adverse effect on their physical and mental health. The most easily perceived manifestations of stress and fear are: physical tension, timidity, avoidance, defense, screaming, barking, etc. At present, there is no better solution and product for pet stress, because pets live alone for a long time and have insufficient contact and interaction time with people, which has a huge impact on their psychology.

[0003] Currently, there are drugs on the market specifically for the acute anxiety and fear experienced by cats during transportation or medical treatment, such as pregabalin solution It has been approved by the EU and the US FDA and is on the market. It is used to relieve acute anxiety and fear of cats related to transportation and veterinary visits. There are also reports on the use of multi-flavor herbal compound for conditioning pets, and the supplementation of nutrients to improve the immunity of pets and indirectly increase the defense level of pets against the harm caused by stress. There are no related products on the market for the above products and methods, and they have obvious shortcomings. Long-term use of drugs will inevitably produce toxic effects, and the quality of the preparation process of traditional Chinese medicine components is difficult to monitor.

[0004] CN114028350B discloses a composition for reducing stress in cats and a preparation method thereof, the core of which is to apply the drug gabapentin to the anti-stress of cats. However, most of these drugs are analgesics and anti-epileptic drugs for human use, which are subject to supervision (for example, the FDA's Freedom of information summary NADA141-580 lists pregabalin as a fifth-category controlled substance), making it inconvenient to use. At the same time, stress in pet dogs and cats is a long-term behavior, which requires long-term administration, and is bound to bring certain toxic side effects to the pet's body.

[0005] CN113476514A discloses an anti-stress composition for cats containing cannabidiol and a preparation method thereof, which comprises the following components by weight: 10-40 parts of Acanthopanax senticosus, 20-50 parts of Citrus aurantium, 20-50 parts of Patchouli, 20-50 parts of Poria, 15-45 parts of Honeysuckle, 15-45 parts of Astragalus, 10-40 parts of Semen Ziziphi Spinosae, 10-40 parts of Schisandrae Chinensis, 10-40 parts of Angelicae Sinensis, and 1-10 parts of cannabidiol. The above patent application mainly uses Chinese herbal medicine as the main functional component, which is compounded with cannabidiol. The preparation process requires repeated decoction of important components, which is complicated and difficult to monitor quality.

[0006] Previous pharmacological studies have shown (Zhang Jilin, 2018) that β-caryophyllene has low water solubility and high affinity for cell membranes. It is a known selective agonist of cannabinoid receptor type 2 (CB2R). Its functions include regulating cytokine release inside and outside the central nervous system, immune cell migration, and protection against thermal nociception. It has local anesthetic, anti-inflammatory, insect repellent, antianxiety, and antidepressant effects.

[0007] Cannabidiol has a weak affinity for the cannabinoid receptor CB1, but a higher affinity for the cannabinoid receptor CB2R, and has multiple pharmacological activities such as anti-tumor, anti-epileptic, immunomodulatory, analgesic, antioxidant, anticonvulsant, and antianxiety (Xie Ran, 2022).

[0008] Bromide can cause hyperpolarization of the cell membrane by competing with chloride ions for transmembrane transport, thereby raising the threshold of epileptic seizures and limiting the conduction of epileptic discharges. It is believed that it can inhibit neuronal excitation and activity. The Chinese Veterinary Pharmacopoeia (2020 edition) stipulates that the dosage for dogs is 0.5 to 2 g when used to relieve symptoms of central nervous system excitability. Summary of the invention

[0009] In view of the problems that existing pet dogs and cats live alone for a long time, are afraid of unfamiliar environments and things, and are prone to stress, the purpose of the present invention is to provide a composition for relieving pet stress and fear and its application.

[0010] In order to achieve the above object, the present invention adopts the following technical solutions:

[0011] A composition for relieving pet stress and fear, the raw materials comprising, by weight percentage: 0.1-20% soothing component, 1-20% amino acid, 0.1-10% antioxidant, 55-90% functionalizing agent, the sum of the weight percentages of all raw materials being 100%;

[0012] The soothing component is a combination of a cannabinoid receptor 2 activator CB2R and bromide;

[0013] The amino acid is one or more of glycine, alanine, valine, leucine, isoleucine, methionine, proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, and taurine;

[0014] The antioxidant is one or more of L-ascorbic acid Vc, d-α-tocopheryl acetate VE, butylated hydroxyanisole BHA, butylated hydroxytoluene BHT, propyl gallate PG, coenzyme Q10, and pyrroloquinoline quinone disodium PQQ;

[0015] The functionalizing agent is selected from vitamins, mineral elements, fatty acids, taste enhancers or dietary fibers.

[0016] Furthermore, the raw materials include, by weight percentage: 0.5-5% soothing component, 5-20% amino acid, 0.5-10% antioxidant, 60-85% functionalizing agent, and the sum of the weight percentages of all raw materials is 100%.

[0017] Furthermore, the mass ratio of the cannabinoid receptor 2 activator to the bromide is 5:1 to 1:100.

[0018] Furthermore, the CB2R activator in the soothing component is β-caryophyllene and / or cannabidiol.

[0019] Furthermore, the bromide in the soothing component is a metal bromide.

[0020] Furthermore, the metal bromide is one or more of sodium bromide, potassium bromide and calcium bromide.

[0021] Furthermore, the CB2R activator is extracted from natural plants or chemically synthesized.

[0022] Furthermore, the source extracted from the natural plants is one or more of basil, black pepper, lavender, rosemary, oregano, hops, cannabis, cinnamon leaf oil, clove leaf oil, vitex oil, and tangerine peel oil.

[0023] The present application also discloses the use of the composition for relieving pet stress and fear in the preparation of oral preparations for pets, wherein the oral preparations are tablets, solutions, powders or semisolid pastes.

[0024] Furthermore, the dosage of the composition for relieving pet stress and fear is calculated based on the pet's weight, with 2 to 10 g of the composition for relieving pet stress and fear being orally administered per 5 kg of pet's body weight per day.

[0025] Principle explanation:

[0026] The CB2R activator (β-caryophyllene or cannabidiol) is used in combination with bromide to produce a synergistic effect, which has a significant anti-stress effect, can make pets behave more calmly, reduce nervousness, timidity, and excitement when facing unfamiliar environments or things, and other behavioral manifestations are normal without special mental inhibition. It can also reduce the dosage of each component, making it safer.

[0027] The combined use of CB2R activators (such as β-caryophyllene, cannabidiol) and bromides (sodium bromide, potassium bromide, etc.) in a ratio of 5:1 to 1:100 can better produce anti-stress and calming effects on pets; however, the effect is unreliable when used alone, and the dosage is often increased to achieve the purpose of application, but excessive dosage can easily cause pets to be overly sedated, and show slow reaction and reduced consciousness.

[0028] Amino acids can support pets in maintaining a healthy immune system and their additional nutrient requirements under stress conditions. The addition of antioxidants, on the one hand, ensures that the main ingredients of the product are protected from oxidative degradation during storage, and on the other hand, can effectively play an antioxidant role when stress factors occur, scavenging free radicals, protecting cells from damage, protecting cell health, stabilizing cell membranes, reducing cell apoptosis and death, and maintaining normal physiological metabolism, which is crucial. Functional agents can provide essential vitamins and minerals for life activities, and at the same time can improve the intestinal environment of pets and aid digestion. The taste enhancer is derived from dried animal products and is used to improve the taste of pets.

[0029] Beneficial effects:

[0030] 1. By acting on different biological targets in the body, the combination of these two drugs can enhance the anti-stress effect;

[0031] 2. To prevent stress, cannabinoid receptor 2 activator, i.e., CB2R activator (β-caryophyllene or cannabidiol) is used in combination with bromide to produce synergistic effect, which has significant anti-stress effect compared with single use of CB2R activator or bromide, and can make pets behave more quietly, reduce nervous, timid, and excited psychological changes when facing unfamiliar environments or things, and other behavioral performances are normal without special mental inhibition performance, and can also reduce the dosage of each component, so that it can be performed more safely. Comparing the test example 1 disclosed in CN113476514A, the results show that the Chinese medicine composition without cannabidiol has better improvements on the sleep quality, mood and feeding of animals, and the combination of adding cannabidiol has no data showing that it has better effects; it can also be seen from the results of test example 2 that there is no significant difference in the recovery of cats after 7 days of stress, whether to add cannabidiol. There are also documents (Qiu Wenyue, 2022) reporting that the treatment of canine idiopathic epilepsy is not a single drug in clinical practice. It is mentioned that potassium bromide (i.e. bromide) or phenobarbital can be used as a combined antiepileptic drug to treat canine idiopathic epilepsy that is still ineffective with the maximum dose of ipitutoin. The optimal serum concentrations of phenobarbital and potassium bromide are 25-35 mg / L and 1500-2000 mg / L, respectively, indicating that the dosage of bromide is very high. Combined with the results of the test examples of the present invention, it can be shown that the combined use of CB2R activators (β-caryophyllene or cannabidiol) and bromides significantly improves the anti-stress effect and reduces the dosage.

[0032] 3. The composition for relieving pet stress and fear of the present invention can be prepared into different oral dosage forms, such as tablets, solutions, powders, semisolid pastes, etc., according to the eating habits and convenience of different animals when used on site, according to methods well known to those skilled in the art;

[0033] 4. The composition for relieving pet stress and fear described in the present invention can be used in daily health care to prevent pet stress, and can also be used clinically when going out, seeking medical treatment or when environmental conditions change dramatically. DETAILED DESCRIPTION

[0034] The present invention is further described in detail below in conjunction with specific examples, but it should not be construed as limiting the present invention. Without departing from the spirit and substance of the present invention, modifications or replacements made to the method, steps or conditions of the present invention all belong to the scope of the present invention. The experimental methods and reagents without specifying the specific conditions in the examples are all in accordance with conventional conditions in the art.

[0035] The β-caryophyllene used in the following examples was from Wuhan Huaxiang Kejie Biotechnology Co., Ltd.; and cannabidiol was from Xi'an Green Biotechnology Co., Ltd.

[0036] Example 1

[0037] A composition for relieving pet stress and fear, the raw materials include, by weight percentage: 0.2% of β-caryophyllene, 2% of sodium bromide, 10% of lysine, 3% of glutamine, 5% of taurine, 3% of Vc, 1% of VE, and coenzyme Q 10 0.5%, BHA 0.1%, xylo-oligosaccharide 20%, chicken powder 40%, glucose 14.7%, magnesium stearate 0.5%, mix well and press into tablets. Take 2-10g orally per 5kg body weight daily.

[0038] Example 2

[0039] A composition for relieving pet stress and fear, the raw materials include, by weight percentage: 0.02% cannabidiol, 2% potassium bromide, 12% lysine, 5% glutamine, 3% taurine, 5% Vc, 0.5% VE, 0.002% PQQ, 0.1% BHA, 15% xylo-oligosaccharide, 55% chicken liver powder, 2.378% glucose, which are uniformly mixed into powder. 2 to 10 g is taken orally per 5 kg body weight per day.

[0040] Example 3

[0041] A composition for relieving stress and fear of pets, comprising the following raw materials by weight percentage: 1% β-caryophyllene, 0.5% potassium bromide, 8% lysine, 3% glutamine, 5% taurine, 3% Vc, 0.8% VE, 0.005% PQQ, 0.1% BHA, 25% xylo-oligosaccharide, 50% chicken liver powder, 3.595% glucose, and the composition is mixed into a semi-solid paste by a wet method using drinking water with 35% dry matter. 2 to 10 g is taken orally per 5 kg body weight per day.

[0042] Example 4

[0043] A composition for relieving pet stress and fear, the raw materials include, by weight percentage: 0.1% cannabidiol, 0.5% sodium bromide, 5% lysine, 4% glutamine, 10% taurine, 5% Vc, 0.8% VE, coenzyme Q 10 0.8%, BHA 0.1%, xylo-oligosaccharide 20%, chicken powder 45%, glucose 8.2%, magnesium stearate 0.5%, mix well and press into tablets. Take 2-10g orally per 5kg body weight daily.

[0044] Example 5

[0045] A composition for relieving pet stress and fear, the raw materials include, by weight percentage: 2% of β-caryophyllene, 0.4% of sodium bromide, 15% of lysine, 2% of glutamine, 3% of taurine, 0.5% of VE, and coenzyme Q 100.5%, BHA 0.1%, xylo-oligosaccharide 25%, chicken powder 50%, glucose 1.5%, mix evenly into powder. Take 2-10g orally per 5kg body weight daily.

[0046] Comparative Example 1

[0047] The difference between this comparative example and Example 1 is that β-caryophyllene is not added.

[0048] The raw material ratio is as follows: sodium bromide 2% (weight percentage, the same below), lysine 10%, glutamine 3%, taurine 5%, Vc 3%, VE 1%, coenzyme Q 10 0.5%, BHA 0.1%, xylo-oligosaccharide 20%, chicken powder 40%, glucose 14.9%, magnesium stearate 0.5%, mix well and press into tablets. Take 2-10g orally per 5kg body weight daily.

[0049] Comparative Example 2

[0050] The difference between this comparative example and Example 4 is that no sodium bromide was added.

[0051] The raw material ratio is as follows: cannabidiol 0.1% (weight percentage, the same below), lysine 5%, glutamine 4%, taurine 10%, Vc 5%, VE 0.8%, coenzyme Q 10 0.8%, BHA 0.1%, xylo-oligosaccharide 20%, chicken powder 45%, glucose 8.7%, magnesium stearate 0.5%, mix evenly and press into tablets. Take 2-10g orally per 5kg body weight daily.

[0052] Test Example 1

[0053] This test example is a test of the effect of the composition of the present invention on improving cat stress

[0054] (I) Test materials

[0055] (1) Test samples: samples prepared in Example 1 (Group I) and Comparative Example 1 (Group II)

[0056] (2) Experimental animals: 10 cats (2 males and 8 females) from a cat breeding kennel.

[0057] (II) Test methods

[0058] (1) Animal inclusion criteria

[0059] 1. Animals aged ≥5 months and weighing ≥2kg;

[0060] 2. The animal has no underlying disease;

[0061] 3. Check to confirm that the female cat is not pregnant or lactating;

[0062] 4. The animals to be selected were put into a simulated transport situation, and the cats were placed in a car for 30 minutes for stress scoring, and the stress score CSS ≥ 3;

[0063] (2) Animal grouping and treatment

[0064] Table 1 Grouping and treatment

[0065]

[0066]

[0067] (3) Test methods

[0068] Before using the product, each cat was put into a car for simulated transportation for 30 minutes, and the score was recorded according to the CSS scoring method in Table 2 (TerttuLamminen, 2023). After continuous use for 15 days according to the grouping treatment method in Table 1, simulated transportation was performed again for 30 minutes and the CSS score was recorded. The difference between the two groups and the difference in CSS before and after use were statistically analyzed. A judgment was made on whether each animal was effective. The judgment was effective if the score was CSS ≤ 2, and invalid if CSS > 2.

[0069] Table 2 Based on cats' stress during transportation (CSS)

[0070]

[0071] (III) Test results

[0072] The scores after continuous feeding of the samples of this embodiment for 15 days are shown in Table 3.

[0073] Table 3 Effectiveness evaluation

[0074]

[0075] Note: * indicates that the score after use is significantly different from that before use (P<0.05); △ It indicates that the scores of group I and group II were significantly different after use (P<0.05).

[0076] The above test results show that the composition of Example 1 of the present invention (Group I) has a significant (P≤0.05) effect of relieving and improving stress for cats with a history of stress or prone to stress, and after use, the stress scores of all 5 (100%) animals were ≤2. There was no significant difference in stress scores before and after use of Comparative Example 1 (Group II) (P>0.05), and only 1 (20%) scored ≤2, and the score of Example 1 was significantly lower than that of Comparative Example 1 after 15 days of use.

[0077] Test Example 2

[0078] This test example is a test of the effect of the composition of the present invention on improving dog stress

[0079] (I) Test materials

[0080] (1) Test samples: samples prepared in Example 4 (Group I) and Comparative Example 2 (Group II)

[0081] (2) Experimental animals: 10 experimental dogs (beagles) and 6 domestic dogs (2 Teddy dogs, 1 Corgi, and 3 Labradors).

[0082] (II) Test methods

[0083] (1) Animal inclusion criteria

[0084] 1. Animals aged ≥ 5 months;

[0085] 2. The animal has no underlying disease;

[0086] 3. Check to confirm that the female dog is not pregnant or lactating;

[0087] 4. The animals to be selected were subjected to simulated car transportation for 60 minutes and subjected to stress scores, with stress scores CSS ≥ 24;

[0088] (2) Animal grouping and treatment

[0089] Table 4 Grouping and treatment

[0090]

[0091] (3) Test methods

[0092] The product was investigated before use. During the test, a stranger carried the experimental dog into a car for simulated transportation for 60 minutes, and then the score was recorded according to the CSS scoring method (FDA Freedom of Information Summary NADA 141-456). After continuous use for 15 days according to the group treatment method, the animals were transported in the same situation again and observed and recorded according to the CSS score. The difference in CSS before and after use was statistically analyzed. A judgment was made on whether each animal was effective. The judgment was valid if the score was CSS <24, and invalid if the score was CSS ≥24.

[0093] According to the scoring criteria in Table 5, the CSS score is calculated for the frequency of the following 12 behavioral signs: panting, trembling, vocalization (including any form of sound such as moaning, barking, growling, howling), pacing (frequently changing positions / running around, restless), seeking humans (clinging, climbing on legs, scratching with claws, trying to sit behind or under, following), trying to hide, trying to escape, freezing (no movement except breathing), refusing to eat food / treats, inappropriate urination (dogs that have been trained to urinate indoors or do not urinate when going out), inappropriate defecation (dogs that have been trained to defecate indoors), drooling. The theoretical maximum total score for each dog is 48.

[0094] Table 5 Based on the stress of dogs during transportation (CSS)

[0095]

[0096]

[0097] (III) Test results

[0098] The scores after continuous feeding of the samples of this embodiment for 15 days are shown in Table 6.

[0099] Table 6 Effectiveness evaluation

[0100]

[0101] Note: * indicates that the score after use is significantly different from that before use.

[0102] The above test results show that the composition of Example 4 (Group I) of the present invention has a good improvement effect on the transportation stress of dogs, and the stress score after use is significantly lower than that before use (P≤0.05). Although the score of Comparative Example 2 (Group II) is lower than that before use, the difference is not significant (P>0.05). According to the evaluation of effectiveness, the effective rate of Example 4 reaches 75% (6 / 8), while the effective rate of Comparative Example 2 is only 37.5% (3 / 8).

[0103] The above test results show that the composition of the present invention can effectively relieve and improve the stress and fear of pet dogs and cats, significantly improve the stress score of animals, and has a high efficiency, allowing animals to return to a normal state. The results of the clinical trial also confirm that the composition of the present invention has significant advantages over the single use of CB2R activators or bromides.

Claims

1. A composition for relieving pet stress and fear, characterized in that: The raw materials include, by weight percentage: 0.1-20% soothing component, 1-20% amino acid, 0.1-10% antioxidant, 55-90% functionalizing agent, and the sum of the weight percentages of all raw materials is 100%; The soothing component is a combination of a cannabinoid receptor 2 activator and a bromide; The amino acid is one or more of glycine, alanine, valine, leucine, isoleucine, methionine, proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, and taurine; The antioxidant is one or more of L-ascorbic acid Vc, d-α-tocopheryl acetate VE, butylated hydroxyanisole BHA, butylated hydroxytoluene BHT, propyl gallate PG, coenzyme Q10, and pyrroloquinoline quinone disodium PQQ; The functionalizing agent is selected from vitamins, mineral elements, fatty acids, taste enhancers or dietary fibers.

2. A composition for relieving pet stress and fear according to claim 1, characterized in that: The raw materials include, by weight percentage: 0.5-5% soothing component, 5-20% amino acid, 0.5-10% antioxidant, 60-85% functionalizing agent, and the sum of the weight percentages of all the raw materials is 100%.

3. A composition for relieving pet stress and fear according to claim 1, characterized in that: The mass ratio of the cannabinoid receptor 2 activator to the bromide is 5:1 to 1:

100.

4. A composition for relieving pet stress and fear according to claim 1, characterized in that: The cannabinoid receptor 2 activator in the soothing component is β-caryophyllene and / or cannabidiol.

5. A composition for relieving pet stress and fear according to claim 1, characterized in that: The bromide in the soothing component is a metallic bromide.

6. A composition for relieving pet stress and fear according to claim 5, characterized in that: The metal bromide is one or more of sodium bromide, potassium bromide and calcium bromide.

7. A composition for relieving pet stress and fear according to claim 4, characterized in that: The cannabinoid receptor 2 activator is extracted from natural plants or chemically synthesized.

8. A composition for relieving pet stress and fear according to claim 7, characterized in that: The natural plant extract is one or more of basil, black pepper, lavender, rosemary, oregano, hops, hemp, cinnamon leaf oil, clove leaf oil, vitex oil, and tangerine peel oil.

9. Use of the composition for relieving pet stress and fear according to any one of claims 1 to 8 in the preparation of a pet oral product, characterized in that: The oral preparation is a tablet, a solution, a powder or a semisolid paste.

10. Use of the composition for relieving pet stress and fear according to claim 9 in preparing a pet oral product, characterized in that: The dosage of the composition for relieving pet stress and fear is calculated based on the pet's weight, and 2 to 10 g of the composition for relieving pet stress and fear is orally administered for every 5 kg of pet's body weight per day.

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