WO2021212700A1 - Pharmaceutical composition for improving motion sickness of pets, preparation method therefor and use method thereof - Google Patents

Abstract

Disclosed are a pharmaceutical composition for improving motion sickness of pets, a preparation method therefor and a use method thereof, which relate to the field of veterinary medicine formulations. The pharmaceutical composition for improving motion sickness of pets comprises the following raw materials in percentage by weight: 10 to 90% of sodium bromide, 2 to 50% of a Ganodorma lucidum extract, 2 to　20% of an oyster extract, 2 to　20% of a spina date seed extract, 1 to 30% of a flavouring agent, and the balance of excipients. The pharmaceutical composition for improving motion sickness of pets of the present invention can significantly improve or relieve vomiting, mental discomfort, as well as abnormal symptoms relating heart rate, respiration and body temperature caused by traveling in vehicles and boats, having relatively high improvement and relief effects. The pharmaceutical composition for improving motion sickness of pets of the present invention can significantly reduce stress of pets. The pharmaceutical composition for improving motion sickness of pets of the present invention can significantly enhance the immunity of pets, and avoid other secondary diseases caused by being fatigued by a long journey.

Description

Pharmaceutical composition for improving pet motion sickness, and preparation method and use method thereof Technical field

The invention relates to the field of veterinary drug preparations, and in particular to a pharmaceutical composition for improving motion sickness of pets, and a preparation method and use method thereof.

Background technique

Motion sickness is medically called "motion sickness". It is a general term for motion sickness and seasickness. It is directly related to the vestibular balance receptors of the inner ear and is a sensitive body's stress response to excessive stimulation. It is manifested in people as dizziness, nausea, vomiting, etc. It can be relieved or recovered by taking a short rest after leaving the car or boat, but it will still cause psychological and physical damage to people, and even cause fear. Some people have After similar experiences, they resisted riding in cars and boats.

With the improvement of living standards and the need for spiritual sustenance, the number of pets has increased year by year, and the population flow due to factors such as breeding transactions, tourism, and family visits tends to be frequent, causing many problems in pet foster care, and many owners choose Carry your pet at any time, so you will inevitably encounter situations such as riding a car. Symptoms such as motion sickness and seasickness also exist in animals, which not only cause symptoms such as dizziness, nausea, and vomiting, but some also show nervousness, fear, depression, etc., poor self-adjustment ability may affect the immune level of pets, and then produce Other diseases. It has been reported (Wang Zhanjiang et al., Henan Animal Husbandry and Veterinary, 22(12), 15-16 (2001)) that the death rate of dogs during long-distance transportation and within 1 to 1.5 months after transportation is 5-8%, sometimes as high as 10 %.

At present, there are many drugs used to treat motion sickness in the field of human medicine, mainly chemical drugs, such as diphenhydramine hydrochloride tablets (the second edition of the Chinese Pharmacopoeia 2015), difentonil hydrochloride tablets (the second edition of the Chinese Pharmacopoeia 2010), and compound hydrogen Scopolamine bromate plaster (the 16th volume of the national standard chemical drug landmark up to the national standard) and so on. At present, there are no products or drugs on the market for improving the symptoms of motion sickness in pets in China, and none of the chemical drugs currently approved for alleviating the symptoms of motion sickness in humans are approved for use in animals or pets. Therefore, there is a need for a safe, stable, and effective drug for improving pet motion sickness.

Summary of the invention

The present invention provides a pharmaceutical composition for improving motion sickness of pets, and a preparation method and use method thereof, and solves the problem that there is no safe, stable, and effective drug for improving motion sickness of pets at present.

In order to solve the above technical problems, the technical solution of the present invention is as follows:

A pharmaceutical composition for improving motion sickness of pets, comprising the following raw materials in weight percentage:

Sodium bromide is 10 to 90%, Ganoderma lucidum extract is 2 to 50%, oyster extract is 2 to 20%, wild jujube seed extract is 2 to 20%, flavor is 1 to 30%, and the balance is excipient.

Sodium bromide is a colorless or white fine cubic crystal or white granular powder. It is analogous to sodium chloride. It competes with bromide ions and chloride ions for transmembrane transport to cause cell membrane hypertrophy, thereby increasing The threshold of epileptic seizures and limits the spread of epileptic discharges. It is clinically used to relieve the excitatory symptoms of the central nervous system, and can be used for animal anticonvulsants and treatment of excitatory diseases such as tetanus.

Ganoderma lucidum extract is derived from the natural fungus Ganoderma lucidum which is homologous in medicine and food. The main active substance is Ganoderma lucidum polysaccharides, which can improve immunity, accelerate blood microcirculation, improve blood oxygen supply capacity, reduce ineffective oxygen consumption in the body at rest, and eliminate Free radicals in the body increase the sealing degree of the cell membrane of the body. At present, it has been made into various health foods, and can also be used as food additives to be added to beverages, cakes, and oral liquids.

Oyster extract is rich in 18 kinds of amino acids extracted from oysters, among which taurine, glutamic acid, arginine, alanine and hydroxyproline are particularly high in content, as well as nucleic acids that can promote the body's metabolism. It has a variety of biological activities, such as improving the body's immunity and increasing the body's anti-fatigue ability. Oysters contain a large amount of taurine and zinc. By increasing the ratio of branched-chain amino acids, increasing the protein synthesis of skeletal muscle, prolonging the appearance of fatigue or reducing the degree of fatigue, it exerts an anti-fatigue effect.

Jujube seed has sedative and hypnotic, antidepressant, anticonvulsant, anti-anxiety, immunity enhancement, and antioxidant effects. The saponins, flavonoids, alkaloids, phenolic acids, and volatile oils in Jujube seed are the main sources of sedation and hypnosis. Active ingredient. Jujube seed extract is a concentrate obtained by extracting wild jujube seed.

Preferably, the weight percentage of the sodium bromide is 20-70%.

Preferably, the weight percentage of the Ganoderma lucidum extract is 5-30%.

Preferably, the weight percentage of the oyster extract is 5-10%.

Preferably, the weight percentage of the extract of jujube seed is 5-20%.

Preferably, the flavoring agent is at least one of chicken powder, chicken liver powder and the like.

Preferably, the excipient is at least one of oral glucose, sucrose or xylo-oligosaccharide.

Preferably, the pharmaceutical composition for improving motion sickness of pets can be made into various dosage forms, such as powders, tablets, capsules, etc., according to methods well known to those skilled in the art.

A method for preparing the pharmaceutical composition for improving motion sickness of pets includes the following steps:

(1) Weigh the Ganoderma lucidum extract, oyster extract and wild jujube seed extract in parts by weight, and place the weighed Ganoderma lucidum extract, oyster extract and wild jujube seed extract in order from less to more parts by weight. Inside the machine, stir and mix for 5-15 minutes to obtain the first premix;

(2) Weigh out sodium bromide, flavors and excipients in parts by weight, and place the weighed flavors and excipients in the mixer in order from less to more parts by weight, and stir to mix 2- 10min; then add the weighed sodium bromide, stir and mix for 5-15min to obtain the second premix;

(3) Put the first pre-mix and the second pre-mix in the mixer in sequence in the order of parts by weight, and stir and mix for 10-20 minutes to obtain the desired pharmaceutical composition for improving pet motion sickness .

A method of using the pharmaceutical composition for improving motion sickness in pets, half an hour before getting on the train, mixing the pharmaceutical composition for improving motion sickness in pets with pet feed or drinking or filling with water, the dosage per pet is 2~ 5g.

By adopting the above technical solution, the pharmaceutical composition for improving motion sickness of pets of the present invention can significantly improve or alleviate pets' vomiting, mental discomfort, heart rate, breathing, body temperature and other abnormal symptoms caused by traveling in cars or boats, and has higher improvement and relief. Effect; the pharmaceutical composition for improving pet motion sickness of the present invention can significantly reduce the stress of pets; the pharmaceutical composition for improving pet motion sickness of the present invention can significantly enhance the immunity of pets, and avoid other diseases due to work in boats and vehicles; the present invention The preparation method of the pharmaceutical composition for improving pet motion sickness uses conventional equipment, and the operation method is simple; the pharmaceutical composition for improving pet motion sickness of the present invention has good palatability and high pet compliance, and can be used by mixing in pet feed or mixing with water. It is easy to use for drinking or filling.

Detailed ways

The specific embodiments of the present invention will be further described below. It should be noted here that the description of these embodiments is used to help understand the present invention, but does not constitute a limitation to the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

The raw materials of the present invention are all commercially available products. The Ganoderma lucidum extract is purchased from Shaanxi Sunfu Natural Products Co., Ltd., the oyster extract is purchased from Nanjing Zelang Biotechnology Co., Ltd., and the wild jujube seed extract is purchased from Xi'an Ruibo Biotechnology Co., Ltd., Chicken liver powder was purchased from Jiangsu Muxiangyuan Animal Health Products Co., Ltd., chicken powder was purchased from Changge Wokai De Food Ingredients Co., Ltd., sucrose was purchased from Nanning Sugar Co., Ltd., and xylo-oligosaccharides were purchased from Shandong Longli Biotech Co., Ltd., sodium bromide was purchased from Nanjing Chemical Reagent Co., Ltd., and oral glucose was purchased from Shanxi Wang Biochemical Technology Co., Ltd.

Example 1

300 g of Ganoderma lucidum extract, 100 g of oyster extract and 100 g of jujube seed extract are placed in a mixer in the order of ascending parts by weight and mixed for 10 minutes to obtain a first premix;

Put 50g chicken liver powder, 50g chicken powder, 100g sucrose and 100g xylo-oligosaccharides in the mixer in the order of ascending weight portion, stir and mix for 5 minutes, then add 200g sodium bromide, stir and mix 10min, get the second pre-mixture;

The first pre-mix and the second pre-mix are placed in a mixer in the order of parts by weight and mixed for 15 minutes to obtain a pharmaceutical composition for improving motion sickness of pets.

Example 2

50g of Ganoderma lucidum extract, 50g of oyster extract, and 50g of jujube seed extract are placed in a mixer in the order of ascending weight, and stirred and mixed for 10 minutes to obtain a first premix;

Put 50g chicken powder, 50g oral glucose and 50g xylo-oligosaccharides in the mixer in ascending order by weight, stir and mix for 5min, then add 150g sodium bromide, stir and mix for 5min, then add 550g of sodium bromide was stirred and mixed for 10 minutes to obtain the second pre-mixture;

The first pre-mix and the second pre-mix are placed in a mixer in the order of parts by weight and mixed for 15 minutes to obtain a pharmaceutical composition for improving motion sickness of pets.

Example 3

100g of Ganoderma lucidum extract, 100g of oyster extract and 50g of jujube seed extract are placed in a mixer in the order of ascending parts by weight, and stirred and mixed for 10 minutes to obtain a first premix;

Put 50g chicken liver powder, 50g chicken powder, 50g sucrose and 100g xylo-oligosaccharides in the mixer in the order of ascending weight, stir and mix for 5 minutes, then add 200g sodium bromide, stir and mix 5min, then add 300g sodium bromide, stir and mix for 10min to obtain the second premix;

The first pre-mix and the second pre-mix are placed in a mixer in the order of parts by weight and mixed for 15 minutes to obtain a pharmaceutical composition for improving motion sickness of pets.

Example 4

100g of Ganoderma lucidum extract, 50g of oyster extract, and 200g of jujube seed extract are placed in a mixer in the order of ascending parts by weight, and stirred and mixed for 10 minutes to obtain a first premix;

Put 100g chicken liver powder, 100g chicken powder, 100g sucrose and 50g xylo-oligosaccharides in the mixer in the order of ascending weight portion, stir and mix for 5 minutes, then add 300g sodium bromide, stir and mix 10min, get the second pre-mixture;

The first pre-mix and the second pre-mix are placed in a mixer in the order of parts by weight and mixed for 15 minutes to obtain a pharmaceutical composition for improving motion sickness of pets.

Example 5

Investigation on the stability of the pharmaceutical composition for improving pet motion sickness of the present invention

In order to determine the stability of the pharmaceutical composition for improving pet motion sickness of the present invention, the pharmaceutical composition for improving pet motion sickness of Example 1, Example 2, Example 3, and Example 4 was tested according to the requirements of "Technical Specification for Stability Test of Veterinary Drugs" The object was subjected to an accelerated test under the following conditions. The pharmaceutical composition for improving motion sickness of pets prepared in Example 1, Example 2, Example 3, and Example 4 was placed in a constant temperature box at a temperature of 40°C and a relative humidity of 75%. Samples were taken for 6 months to observe the properties, loss on drying and determine the sodium bromide content. The test results are as follows:

Table 1: Stability test results of the pharmaceutical composition for improving pet motion sickness of Example 1

project

Traits

Loss on drying (%)

NaBr content (%)

0 month	Light yellow powder	3.2	19.8
January	Light yellow powder	3.4	19.8
February	Light yellow powder	3.3	19.7
March	Light yellow powder	3.5	19.5
June	Light yellow powder	3.7	19.3

Table 2: Stability test results of the pharmaceutical composition for improving pet motion sickness of Example 2

project	Traits	Loss on drying (%)	content(%)
0 month	Off-white powder	2.4	70.3
January	Off-white powder	2.4	70.1
February	Off-white powder	2.5	70.1
March	Off-white powder	2.5	70.0
June	Off-white powder	2.7	69.7

Table 3: Stability test results of the pharmaceutical composition for improving pet motion sickness of Example 3

project	Traits	Loss on drying (%)	content(%)
0 month	Off-white powder	2.8	50.4
January	Off-white powder	2.8	50.3
February	Off-white powder	2.9	50.1
March	Off-white powder	3.0	49.9
June	Off-white powder	3.2	49.5

Table 4: Stability test results of the pharmaceutical composition for improving pet motion sickness of Example 4

project	Traits	Loss on drying (%)	content(%)
0 month	Light yellow powder	3.0	30.0
January	Light yellow powder	3.0	29.8
February	Light yellow powder	3.2	29.7
March	Light yellow powder	3.3	29.5
June	Light yellow powder	3.5	29.3

From the above accelerated test results, the pharmaceutical compositions of Examples 1, 2, 3, and 4 for improving pet motion sickness have no changes in their properties during the accelerated stability test period, and there are no significant changes in drying loss and content, indicating that The pharmaceutical composition for improving motion sickness of pets of the present invention is stable.

Example 6

Safety test on dogs of the pharmaceutical composition for improving pet motion sickness of the present invention

(1) Test materials

(1) Test drug: The pharmaceutical composition for improving motion sickness of pets prepared in Example 2.

(2) Experimental animals: healthy general-grade Beagle dogs, weighing 10-12kg, 6 dogs, half male and half male, Suzhou Xishan Zhongke Experimental Animal Co., Ltd. (Experimental Animal Production License Number: SCXK (苏) 2018-0001).

(2) Test method

In this experiment, the self-control method was used to feed 6 dogs with the highest dose: 5g/head/time for 7 consecutive days, collected before and after treatment (day 0) and after treatment (day 8). Venous blood is routinely tested, and changes in the dog's spirit, appetite, breathing, and feces are observed every day.

(3) Test results

(1) Changes in clinical symptoms

Through observation after administration according to the designed plan, it was found that after 7 days of continuous use, no abnormal reactions were seen in dogs, such as resistance, excitement, etc. during the administration period. During the whole experiment, the dogs were quiet, eating normally, breathing smoothly, and had smooth hair. No abnormal clinical manifestations were observed.

(2) Measurement results of blood routine

Table 5 Blood routine results before and after the test

Blood routine index	Day 0	Day 8
White blood cell WBC (×10 9 /L)	11.28±1.60	11.00±1.57
Red blood cell RBC (×10 12 /L)	5.94±0.53	6.01±0.65
Hemoglobin Hb(g/L)	125.32±8.64	126.33±11.24
Platelet PLT (×10 9 /L)	265.50±32.18	245.24±23.27
Hematocrit HCT	0.33±0.02	0.32±0.02

Judging from the safety test results of dogs, the pharmaceutical composition for improving pet motion sickness of the present invention has no effect on the clinical performance and blood routine indexes of dogs, indicating that the pharmaceutical composition for improving pet motion sickness of this group can be used safely.

Example 7

Field test of the pharmaceutical composition for improving motion sickness of pets in improving the symptoms of motion sickness in dogs

(1) Test materials

(1) Test drug: The pharmaceutical composition for improving motion sickness of pets prepared in Example 2.

(2) Experimental animals: healthy general-grade Beagle dogs, weighing 10-12kg, 12, male and female, Suzhou Xishan Zhongke Experimental Animal Co., Ltd. (Experimental Animal Production License Number: SCXK (Su) 2018-0001).

(2) Test method

The 12 dogs were randomly divided into two groups, each with 6 dogs, half male and half female. One group is the control group without any treatment, and the other group is the test group 30 minutes before transportation, each dog is fed 2g of test drug per dog, and long-distance transportation (70-80km/h) is carried out by ordinary van for 4h. The heart rate, respiration, body temperature, mental score, and vomiting score of each dog in the two groups were measured before and after transportation. Venous blood was collected before and after transportation to determine cortisol (COR) and corticotropin (ACTH).

Table 6 Scoring criteria for vomiting

degree	situation	score
normal	No vomiting	0
Mild	1 time within 24h	3
Moderate	2～5 times within 24h	6
Severe	6～10 times within 24h	9
severe	More than 10 times within 24h	12

Note: The occurrence of vomiting is counted as 1 vomiting, continuous vomiting or discontinuous vomiting within 1 min is also counted as 1 vomiting.

Table 7 Mental State Scoring Criteria

degree	situation	score
normal	Lively,	0
Mild	Quiet, less activity	1
Moderate	Standing still, decreased responsiveness to external disturbances	2
Severe	Lethargy, after driving away activities	3
severe	Lethargy, reluctance to move after driving	4

(3) Test results

By observing and comparing the indicators before and after transportation in the test group and the control group, it was found that two dogs in the blank control group had vomiting, and all dogs had different degrees of mental discomfort, but the mental and vomiting scores of the test group were 0, and the test The heart rate, respiration and body temperature of the dogs in the group did not change significantly, but the heart rate and respiration of the control group increased significantly, and the body temperature also increased.

Table 8 Changes in clinical symptoms

Table 9 Changes in blood indicators

It can be seen from the above results that the pharmaceutical composition for improving pet motion sickness of the present invention can effectively alleviate and improve the stress response of the respiratory system and blood system of the pet after transportation, reduce mental symptoms and vomiting, and reduce fluctuations in related hormone levels , Thereby improving the symptoms of motion sickness.

The embodiments of the present invention have been described in detail above, but the present invention is not limited to the described embodiments. For those skilled in the art, without departing from the principle and spirit of the present invention, various changes, modifications, substitutions and modifications to these embodiments still fall within the protection scope of the present invention.

Claims (10)

1. A pharmaceutical composition for improving motion sickness of pets, which is characterized in that it comprises the following raw materials in weight percentage:

   Sodium bromide is 10 to 90%, Ganoderma lucidum extract is 2 to 50%, oyster extract is 2 to 20%, wild jujube seed extract is 2 to 20%, flavor is 1 to 30%, and the balance is excipient.
2. The pharmaceutical composition for improving motion sickness of pets according to claim 1, wherein the weight percentage of sodium bromide is 20-70%.
3. The pharmaceutical composition for improving motion sickness of pets according to claim 1, wherein the weight percentage of the Ganoderma lucidum extract is 5-30%.
4. The pharmaceutical composition for improving motion sickness of pets according to claim 1, wherein the weight percentage of the oyster extract is 5-10%.
5. The pharmaceutical composition for improving motion sickness of pets according to claim 1, wherein the weight percentage of the extract of jujube seed is 5-20%.
6. The pharmaceutical composition for improving motion sickness of pets according to claim 1, wherein the flavoring agent is at least one of chicken powder and chicken liver powder.
7. The pharmaceutical composition for improving motion sickness in pets according to claim 1, wherein the excipient is at least one of oral glucose, sucrose or xylo-oligosaccharides.
8. The pharmaceutical composition for improving motion sickness of pets according to any one of claims 1-7, wherein the dosage form of the pharmaceutical composition for improving motion sickness of pets is powder, tablet or capsule.
9. A method for preparing a pharmaceutical composition for improving motion sickness in pets according to any one of claims 1-8, characterized in that it comprises the following steps:

   (1) Weigh the Ganoderma lucidum extract, oyster extract and wild jujube seed extract in parts by weight, and place the weighed Ganoderma lucidum extract, oyster extract and wild jujube seed extract in order from less to more parts by weight. Inside the machine, stir and mix for 5-15 minutes to obtain the first premix;

   (2) Weigh out sodium bromide, flavors and excipients in parts by weight, and place the weighed flavors and excipients in the mixer in order from less to more parts by weight, and stir to mix 2- 10min; then add the weighed sodium bromide, stir and mix for 5-15min to obtain the second premix;

   (3) Put the first pre-mix and the second pre-mix in the mixer in sequence in the order of parts by weight, and stir and mix for 10-20 minutes to obtain the desired pharmaceutical composition for improving pet motion sickness .
10. A method for using the pharmaceutical composition for improving motion sickness in pets according to any one of claims 1-8, wherein the pharmaceutical composition for improving motion sickness in pets is mixed with pet feed or after mixing with water half an hour before getting on the train. For drinking or gavage, the dosage for each pet is 2~5g.