CN116832098A

CN116832098A - Skin-soothing flavor tablet for dogs as well as preparation method and application thereof

Info

Publication number: CN116832098A
Application number: CN202210291516.0A
Authority: CN
Inventors: 晏磊; 何佳丽; 胡晖建
Original assignee: Luoyang Lechong Health Technology Co ltd
Current assignee: Luoyang Lechong Health Technology Co ltd
Priority date: 2022-03-23
Filing date: 2022-03-23
Publication date: 2023-10-03

Abstract

The invention relates to the technical field of pet medicines, in particular to a canine skin soothing flavor tablet, a preparation method and application thereof. The skin soothing flavor tablet for dogs contains fructus Xanthii extract, fructus Cnidii extract, flos Lonicerae extract, herba seu radix Cirsii Japonici extract, herba Schizonepetae extract, radix Rubiae extract, carthami flos extract, herba Solani Lyrati extract, silicon dioxide and microcrystalline cellulose, and has unique formula, and can rapidly relieve itching and relieve erythra degree, and has high palatability.

Description

Skin-soothing flavor tablet for dogs as well as preparation method and application thereof

Technical Field

The invention relates to the technical field of pet medicines, in particular to a canine skin soothing flavor tablet, a preparation method and application thereof.

Background

According to white paper of the medical treatment channel of the pets in 2021, the first three conditions of the treatment of dogs to the hospitals of the pets are respectively digestive system, skin diseases and infectious diseases, the skin diseases of the dogs are located at the second position, the treatment amount of the skin diseases of the dogs accounts for 11.04% of the total treatment amount, the incidence rate of the skin diseases of the dogs is higher than that of cats, meanwhile, the incidence rate increasing trend and the incidence rate decreasing trend of the skin diseases of the dogs are more obvious, periodicity exists, and the high incidence period is concentrated in summer and autumn, and can be relieved in spring and winter. The proportion of skin diseases in medium dogs is far greater than in large dogs and small dogs. After skin diseases of dogs, skin itching, scratching, inflammation (hair loss, skin redness, dander, skin mossiness, pimple and the like) and the like are accompanied, and the dogs are malignant circulation, and the scratching can cause scratching, the scratching can cause inflammation, and the inflammation can cause further itching, so that the physical and mental health of dogs and pets can be endangered.

The main causes of canine skin disease are 4 as follows: bacterial infection, fungal infection, food allergy and atopic dermatitis. Most canine skin diseases can cause malignant cycles of itching, scratching, skin inflammation and the like, so that the problems of itching, scratching and skin inflammation are solved for canine skin diseases. The existing antipruritic drugs in the market comprise various types such as histamine, hormones, JAK inhibitors, immunosuppressants, monoclonal antibody injections and the like, wherein the histamine, the hormones and the JAK inhibitors have certain toxic and side effects and cannot be used for a long time; the immunosuppressant has slow effect and has no obvious effect on acute pruritus and acute atopic dermatitis; monoclonal antibody injection has fast antipruritic effect, but does not solve the problem of skin inflammation, and has very high price, and has not been marketed in China yet. At present, a preparation which has high safety and quick antipruritic effect on canine skin diseases and has a therapeutic function on skin inflammation is lacking in China.

At present, related products sold on the market comprise jazz pet health, alatinib epstein tablet, chlorpheniramine maleate tablet and the like, wherein the components of the jazz pet health comprise compound vitamins, evening primrose oil, lecithin, linoleic acid, natural plants such as peppermint, astragalus and the like, and a plurality of clinical pet doctors are found to feed back in the field investigation, so that the functionality and the palatability are poor; the components of the Alatinib maleate tablet comprise Alatinib maleate, which has quick antipruritic effect but does not solve inflammatory reaction caused by allergy, has certain toxic and side effects, is less than 12 months old and can not be used by pregnant dogs; the chlorpheniramine maleate tablet comprises chlorpheniramine maleate, is mainly aimed at inflammation caused by skin allergy, has no obvious effect on pruritus, and has certain side effects on respiratory tract and digestive tract.

In view of this, the present invention has been made.

Disclosure of Invention

The first object of the present invention is to provide a canine skin soothing flavor tablet.

The second object of the present invention is to provide the use of the canine skin soothing flavor tablet.

The third object of the present invention is to provide a method for producing the canine skin soothing flavor tablet.

The fourth object of the invention is to provide a canine skin soothing drug.

In order to achieve the above purpose, the present invention adopts the following technical scheme:

the skin soothing flavor tablet for dogs comprises the following components in percentage by weight: 0.25 to 3.75 percent of cocklebur fruit extract, 0.25 to 3.75 percent of fructus cnidii extract, 1.5 to 2.0 percent of honeysuckle extract, 1.0 to 1.5 percent of Japanese thistle extract, 1.0 to 2.0 percent of herba schizonepetae extract, 0.25 to 4.25 percent of madder root extract, 1.5 to 3.05 percent of safflower extract, 0.75 to 3.15 percent of white nightshade extract and 0.1 to 1.0 percent of silicon dioxide, and the balance of microcrystalline cellulose.

Further, the skin soothing flavor tablet for dogs comprises the following components in percentage by weight: 3.25 to 3.75 percent of fructus xanthil extract, 3.25 to 3.75 percent of fructus cnidii extract, 1.75 percent of honeysuckle extract, 1.25 percent of herba seu radix Cirsii Japonici extract, 1.5 percent of herba schizonepetae extract, 1.25 to 4.25 percent of radix rubiae extract, 3.05 percent of safflower extract, 2.15 to 3.15 percent of white nightshade extract, 0.5 percent of silicon dioxide and the balance of microcrystalline cellulose.

Further, the skin soothing flavor tablet for dogs comprises the following components in percentage by weight:

fructus Xanthii extract 3.25%, fructus Cnidii extract 3.25%, flos Lonicerae extract 1.75%, herba seu radix Cirsii Japonici extract 1.25%, herba Schizonepetae extract 1.50%, radix Rubiae extract 1.25%, carthami flos extract 3.05%, herba Solani Lyrati extract 2.15%, silicon dioxide 0.50% and microcrystalline cellulose 82.05%;

or fructus Xanthii extract 3.75%, fructus Cnidii extract 3.75%, flos Lonicerae extract 1.75%, herba seu radix Cirsii Japonici extract 1.25%, herba Schizonepetae extract 1.50%, radix Rubiae extract 4.25%, carthami flos extract 3.05%, herba Solani Lyrati extract 3.15%, silicon dioxide 0.50% and microcrystalline cellulose 77.05%.

Further, the skin soothing flavor tablet for dogs comprises 13-17% of flavoring agent, preferably 15% of flavoring agent by weight percent.

Further, the flavoring agent comprises at least one of chicken liver powder, hydrolyzed chicken liver powder, beef powder and canine taste enhancer.

Further, the flavoring agent is hydrolyzed chicken liver powder and/or canine taste enhancer, preferably hydrolyzed chicken liver powder.

The application of the canine skin soothing flavor tablet in preparing canine skin soothing drugs.

Further, skin relief includes relief of itching and relief of rash.

The preparation method of the canine skin soothing flavor tablet comprises the steps of uniformly mixing the raw materials according to the proportion, and tabletting to obtain the canine skin soothing flavor tablet.

The canine skin soothing drug comprises the canine skin soothing flavor tablet.

Compared with the prior art, the invention has the beneficial effects that:

the skin-soothing flavor tablet for dogs provided by the invention is a traditional Chinese medicine formula, has a unique formula, can quickly relieve itching and alleviate the degree of erythema, has high palatability, is willing to actively feed by dogs, and solves the problem of feeding difficulty. Experimental data show that after the canine skin soothing flavor tablet disclosed by the invention is used, the pruritus is obviously reduced after 4 hours, the pruritus is recovered to a normal level after 7 days, and the effective rate of relieving the erythema is up to more than 90%.

Detailed Description

The following describes specific embodiments of the present invention in detail.

The invention provides a skin-soothing flavor tablet for dogs, which comprises the following components in percentage by weight: 0.25 to 3.75 percent of cocklebur fruit extract, 0.25 to 3.75 percent of fructus cnidii extract, 1.5 to 2.0 percent of honeysuckle extract, 1.0 to 1.5 percent of Japanese thistle extract, 1.0 to 2.0 percent of herba schizonepetae extract, 0.25 to 4.25 percent of madder root extract, 1.5 to 3.05 percent of safflower extract, 0.75 to 3.15 percent of white nightshade extract and 0.1 to 1.0 percent of silicon dioxide, and the balance of microcrystalline cellulose.

The canine skin soothing flavor tablet provided by the invention takes the traditional Chinese medicines as the active ingredients, has high safety, realizes effective synergistic effect by applying the traditional Chinese medicine theory through the components in the proportion, improves the problems of canine skin itch, skin inflammation and the like, and reduces the damage of skin diseases to dogs. Experiments show that: the skin-soothing flavor tablet for dogs can quickly relieve itching, has quick response, obviously reduces itching after 4 hours, and returns to normal itching after 7 days; can quickly slow down the erythema degree, obviously reduces the erythema degree in 3 days, has the effective rate of more than 90 percent in 7 days, has obvious efficacy and is superior to most of products on the market.

The content of the fructus Xanthii extract may be, but is not limited to, 0.25%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.25%, 3.3%, 3.4%, 3.5%, 3.6% or 3.75%; the content of the cnidium fruit extract may be, but is not limited to, 0.25%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.25%, 3.3%, 3.4%, 3.5%, 3.6% or 3.75%; the content of the honeysuckle extract can be, but is not limited to, 1.5%, 1.6%, 1.7%, 1.8%, 1.9% or 2%; the content of the Cirsium japonicum extract may be, but is not limited to, 1%, 1.1%, 1.2%, 1.3%, 1.4% or 1.5%; the content of herba Schizonepetae extract can be, but is not limited to, 1%, 1.2%, 1.4%, 1.6%, 1.8% or 2%; the content of the madder extract may be, but is not limited to, 0.25%, 0.5%, 1%, 1.25%, 1.5%, 1.75%, 2%, 2.25%, 2.5%, 2.75%, 3%, 3.25%, 3.5%, 3.75%, 4% or 4.25%; the content of safflower extract may be, but is not limited to, 1.5%, 1.75%, 2%, 2.25%, 2.5%, 2.75% or 3.05%; the content of the solanum dulcamara extract may be, but is not limited to, 0.75%, 1%, 1.25%, 1.5%, 1.75%, 2%, 2.25%, 2.5%, 2.75% or 3.15%; the silica content may be, but is not limited to, 0.1%, 0.25%, 0.5%, 0.75% or 1%.

Each traditional Chinese medicine component in the canine skin soothing flavor tablet is a commercial raw material, and specific information is as follows.

The fructus Xanthii extract is dry mature fruit extract of Xanthium sibiricum of Compositae, and has brown powder, and mainly contains heterocyclic compounds such as volatile oil, fatty oil, phenolic acid, xanthone, anthraquinone, flavone, alkaloid, and other components. Has antibacterial, analgesic, antitumor, antioxidant, antiinflammatory, antiviral, and blood glucose lowering effects.

The fructus Cnidii extract is fruit extract of fructus Cnidii of Umbelliferae, and has brown yellow powder, and contains pinene, iso-valyl ester, parsley phenol methyl ether, dihydro-Parsley alcohol, bergapten, osthole, and iso-pimpinellin as effective components.

The flos Lonicerae extract is dried flower bud or flower with primary opening of Lonicera japonica of Caprifoliaceae, and has brown powder and chlorogenic acid as main ingredient.

The Cirsium japonicum extract is aerial part extract of Cirsium japonicum of Compositae, and has brown yellow powder, and contains volatile oil and alkaloid.

The herba Schizonepetae extract is prepared from whole plant of herba Schizonepetae of Labiatae, and has the shape of brown powder and volatile oil. The herba Schizonepetae extract also has certain inhibiting effect on Bacillus anthracis, streptococcus B, typhoid bacillus, bacillus dysenteriae, pseudomonas aeruginosa and human type tubercle bacillus.

The Rubia cordifolia extract is yellow brown powder extracted from root and rhizome of Rubia cordifolia of Rubiaceae, and mainly contains anthraquinone, naphthoquinone, alizarin, and iridoid. It is commonly used for hematemesis, epistaxis, metrorrhagia, leukorrhagia, traumatic hemorrhage, amenorrhea, arthralgia, and traumatic injury.

The safflower extract is dry flower extract of Compositae plant safflower, has the shape of brown yellow powder, mainly contains various active ingredients such as flavonoid substances, fatty acids, pigments, phenolic acids, volatile oil, etc., and is widely used in food, beverage, cosmetics, pharmacy, and printing industry.

The Solanum dulcamara extract is whole plant extract of Solanum dulcamara of Solanaceae, and has brown yellow powder, and mainly contains solanine, anthocyanin and aglycone. It has effects of clearing heat, promoting diuresis, removing toxic substances, relieving swelling, and resisting cancer.

In a preferred embodiment, the skin soothing flavor tablet for dogs consists of the following components in weight percent: 3.25 to 3.75 percent of fructus xanthil extract, 3.25 to 3.75 percent of fructus cnidii extract, 1.75 percent of honeysuckle extract, 1.25 percent of herba seu radix Cirsii Japonici extract, 1.5 percent of herba schizonepetae extract, 1.25 to 4.25 percent of radix rubiae extract, 3.05 percent of safflower extract, 2.15 to 3.15 percent of white nightshade extract, 0.5 percent of silicon dioxide and the balance of microcrystalline cellulose.

In a more preferred embodiment, the skin soothing flavor tablet for dogs consists of the following components: fructus Xanthii extract 3.25%, fructus Cnidii extract 3.25%, flos Lonicerae extract 1.75%, herba seu radix Cirsii Japonici extract 1.25%, herba Schizonepetae extract 1.50%, radix Rubiae extract 1.25%, carthami flos extract 3.05%, herba Solani Lyrati extract 2.15%, silicon dioxide 0.50% and microcrystalline cellulose 82.05%;

In a preferred embodiment, the skin soothing flavor tablet for dogs may further comprise 13% -17% flavoring agent, preferably 15% flavoring agent. Wherein the flavoring agent is preferably at least one of chicken liver powder, hydrolyzed chicken liver powder, beef powder and flavoring agent for dogs. Further preferred are hydrolyzed chicken liver powder and/or a taste enhancer for dogs, and more preferred is hydrolyzed chicken liver powder.

The flavoring agent can improve the palatability of the product and promote animals to eat actively, and experiments show that the flavoring agent provided by the invention can improve the palatability of the product by 2.8-6.8 times.

The hydrolyzed chicken liver powder is prepared by adopting fresh chicken liver as a raw material and refining and drying the fresh chicken liver by advanced biotechnology, and the due flavor and color of the chicken liver are maintained.

The taste enhancer is a commercial raw material and can be used for enhancing the flavor of products, such as taste enhancers produced by Shanghai He Pu Utility company, ming (China) technology Co., shanghai Yebang biotechnology Co., shandong Euro biotechnology Co., and the like.

Based on the above, the canine skin relief flavor tablet provided by the invention can be used for preparing canine skin relief medicines, and specifically comprises the effects of relieving itching, reducing inflammation such as erythra and the like. Meanwhile, the invention provides a skin soothing drug for dogs, which contains the skin soothing flavor tablet for dogs, and can also comprise other functional components, such as a commercially available external medicine and the like.

The invention also provides a preparation method of the skin-soothing flavor tablet for dogs, which comprises the steps of uniformly mixing the raw materials according to the proportion, and tabletting to obtain the skin-soothing flavor tablet for dogs. Since the components are all in powder form and are matched with specific silicon dioxide and microcrystalline cellulose, a powder direct compression process can be adopted.

The existing common preparation processes are wet granulation tabletting and dry granulation tabletting, wherein the wet granulation tabletting process steps comprise weighing, mixing, wet granulation, drying, finishing, total mixing and tabletting, wherein the wet granulation and drying can cause loss of functional components, the process is complex, the drying time is long, and generally 2-6 hours are required; the dry granulating and tabletting process comprises the following steps: weighing, crushing, sieving, mixing, briquetting, crushing, granulating, mixing and tabletting, namely, raw and auxiliary materials are crushed into particles after being pressed into blocks, and then tabletting is carried out, so that the problems of complex process, high requirement on the granularity after crushing and the like exist.

The invention will be further described in connection with specific examples, but is not limited to the examples.

Example 1 formulation and preparation method of skin soothing flavor tablet for dogs

1.1 formula of skin soothing flavor tablet for dogs

Through repeated experiments, the microcrystalline cellulose in the formula of the skin-soothing flavor tablet for dogs is found to be between 30 and 95 percent w/w, and the microcrystalline cellulose has no obvious influence on the functionality of the whole formula. Under the condition of ensuring 100% w/w of the total formulation, 6 formulations of the canine skin soothing flavor tablets are prepared, and microcrystalline cellulose in the formulations is adjusted, wherein the raw materials used in the formulations are all commercial raw materials.

TABLE 1 formulation for skin soothing flavor tablets for dogs

1.2 preparation method

The preparation method of the skin soothing flavor tablet for dogs comprises the following steps: a total of 3 process steps: weighing, mixing and tabletting, wherein the components are weighed according to the formula, poured into a mixer for mixing and stirring, and transferred to a tablet press for tabletting after being stirred uniformly.

1.3 preparation of skin soothing flavor tablet for dogs

The canine skin soothing flavor tablet formulas 1-6 described in the example 1.1 are respectively prepared into canine skin soothing flavor tablets 1-6 according to the preparation method described in the example 1.2, and the weight difference of the flavor tablets 5 exceeds +/-5% according to the requirements of Chinese veterinary pharmacopoeia (two parts) on tablets, and does not accord with the regulations of Chinese veterinary pharmacopoeia; the disintegration time of the flavor tablet 6 exceeds 30 minutes and does not meet the requirements of Chinese animal pharmacopoeia, so that the flavor tablet which is finally molded well comprises the flavor tablet 1, the flavor tablet 2, the flavor tablet 3 and the flavor tablet 4.

Example 2 evaluation of the functionality of skin soothing flavor tablets for dogs

It is well known to those skilled in the art that SPF grade BALB/c mice can be used for animal replacement experiments for initial screening of flavor chip formulations.

2.1 pruritus model establishment

2.1.1 grouping of laboratory animals

64 SPF-class BALB/c mice were selected, females weighing 20-25g, and provided by the medical laboratory animal center in Guangdong province, and given 3d adaptive feeding. Laboratory temperature (24+ -2) deg.C, relative humidity 55% -65%. The circadian time was controlled at 12h each. The 64 mice were randomly divided into a blank group and a model group according to body weight, wherein 8 mice in the blank group and 56 mice in the model group.

2.1.2 preparation before experiment

2, 4-Dinitrochlorobenzene (DNCB) was dissolved in an acetone/olive oil (volume ratio 1:4) base solution to prepare DNCB sensitization solutions having a concentration of 1% (volume ratio) and 2% (volume ratio), respectively.

2.1.3 pruritus model establishment method

Except for the blank group, the model group needs to be modeled. All mice were shaved on their abdomen 2d prior to the experiment to an area of approximately 2.5cm by 2.5cm. The mice were applied to their abdomen shaved areas and ears on day 1 of the experiment with 100 μl of 2% dncb acetone solution, untreated on days 2-4 of the experiment, and applied to their abdomen shaved areas and ears on day 5 instead of 100 μl of 1% dncb acetone solution, followed by 1 stimulation every 3 days for 21 days for a total of 7 stimulations. The abdomen shaved area and the ears of the mice in the blank group are only coated with the acetone/olive oil matrix solution, and the coating time and the coating dosage are consistent with those of the model group.

2.1.4 detection index:

2.1.4.1 the number of mouse scratching times

The mice of each group were placed in a single cage and the number of scratches of the mice was counted for 10 min. The continuous scratching of the ear and abdomen by the hind limb was regarded as 1 scratching event, and the time when the hind paw fell to the ground or was licked, the scratching was ended. The movements of the forelimbs and scratching on the opposite side of the hind paw, back, etc. were not counted. The total number of observations was 1 on each of day 1 of the experiment (within 1h after 1 stimulation of DNCB), day 5 of the experiment (within 1h after 2 stimulation of DNCB), and day 21 of the experiment, 3 times.

2.1.4.2 mice skin loss phenomenon scoring

The mice of each group were visually observed and scored for skin lesions on day 1 and day 21, and the scoring criteria were as shown in table 2 below, after multiple trial and error.

Table 2 mice abdomen skin loss scoring table

2.1.4.3 weight change in mice

The body weights of the mice in each group were measured on day 1 and day 21, respectively.

2.1.5 statistical methods

Statistical treatment is carried out on the test data by using SPSS18.0 software, repeated measurement analysis of variance or single factor analysis of variance is adopted for comparison between groups, and then LSD test is carried out for comparison between the two groups; when normal distribution and variance uniformity are not satisfied, a Kruskal-Wallis H rank sum test is used.

2.1.6 experimental results

Comparison of scratch times of mice of different groups of 2.1.6.1

TABLE 3 comparison of scratch counts at each observation point for each group of mice

Note that: compared to the blank: * P <0.05, P <0.01.

As shown in table 3, on day 5 of the experiment, the number of mice in the model group was significantly increased (P < 0.01) compared to the blank group, and on day 21 of the experiment, the number of mice in the model group was still significantly higher than the blank group (P < 0.01).

Comparison of body weight of mice of different groups of 2.1.6.2

Table 4 comparison of body weight at each observation point for each group of mice

Note that: compared to the blank: * P <0.05, P <0.01.

As shown in table 4, the weights of mice on day 1 of the experiment were compared with the weights of mice on day 21 of the experiment, and the weights of the two groups of mice were not statistically different (P > 0.05); there was no statistical difference in the difference in weight gain between the two groups of mice (P > 0.05).

2.1.6.3 abdominal skin lesion manifestation in mice of different groups

The abdominal skin of the mice on day 1 and day 21 was evaluated accordingly according to the scoring criteria in table 2. The results are shown in Table 5.

Table 5 comparison of abdominal skin lesions in two groups of mice

On day 21 of the experiment, the skin of the abdomen of the mice in the blank group was not substantially changed, only slight flushing and edema, and no rash, exudation and crusting were observed. The abdomen skin of the mice in the model group has obvious erythema, edema and exudation, and the partial erosion surface gradually forms scab, so that the scab skin with different yellow thickness can be seen, and the skin loss phenomena such as local dryness, desquamation, epidermis thickening and the like can be seen.

In summary, the analysis of the data of the number of scratching times of the mice shows that the blank group and the model group have significant differences, and the comparison of the skin damage phenomenon of the mice shows that the blank group and the model group have large differences, which indicates that the pruritus model group is established and can be used for the subsequent flavor slice evaluation test.

2.2 test of functional evaluation of flavor chips 1-4 on pruritus model

The 56 mice of the pruritus model group of example 2.1 were randomly divided into 7 groups, 8/group, and flavor chip functionality evaluation was performed simultaneously with the normal control group (8, group 1). Specifically, each mouse in group 2 was intraperitoneally injected with 0.5ml of physiological saline daily as a control group for itching; each mouse in group 3 was intraperitoneally injected with 0.5ml of physiological saline containing 0.25g/kg of the final content of flavor tablet 1 every day; each mouse in group 4 was intraperitoneally injected with 0.5ml of physiological saline containing 0.25g/kg of flavor tablet 2 as a final content every day; each mouse in group 5 was intraperitoneally injected with 0.5ml of physiological saline containing flavor tablet 3 at a final content of 0.25g/kg each day; each mouse in group 6 was intraperitoneally injected with 0.5ml of physiological saline containing 0.25g/kg of flavor tablet 4 as a final content every day; each mouse of group 7 was intraperitoneally injected with 0.5ml of physiological saline containing 0.25g/kg of Aibo (3.6 mg, available from Ascow pharmaceutical Co., of Buddha, buddha). Each mouse of group 8 was intraperitoneally injected with 0.5ml of physiological saline containing pet health (purchased from pet information technologies (Shanghai) Co., ltd.) at a final content of 0.25g/kg every day. Groups 2-8 continued for 21 days of treatment. Statistical analysis was performed on the number of itching and the index of change in body weight of each animal on the day before treatment (day 0) and on the day after treatment (day 22), and the skin loss phenomenon was observed, and the results are shown in tables 6, 7 and 8.

Table 6 comparison of scratch counts at each observation point of mice

Note that: compared to the blank: * P <0.05, < P <0.01; compared with the pruritus control group: Δp <0.05, Δp <0.01.

See table 6, there were very significant differences in the number of pruritus between groups 2-8 and blank (i.e., group 1, normal control) on the day prior to treatment. After the treatment is finished, the 3 rd group, the 4 th group and the 8 th group have no significant difference from the pruritus control group; the day after treatment, the number of scratching times in groups 5-7 were significantly different from that in the itching control group and were similar to that in the blank group. The flavor tablet 3, the flavor tablet 4 and the control group of ibok are obvious in treatment effect on the pruritus mice.

Table 7 comparison of body weight at each observation point of mice

See table 7, no significant differences in body weight were observed between groups 2-8 and the blank mice on the day prior to treatment. After the treatment, the weights of the mice in the groups 3-8 and the pruritus control groups are not significantly different. There was a trend of decrease in body weight before and after treatment for groups 5-7, but no significant difference.

The abdominal skin lesions before and after 8 groups of treatments were scored according to the abdominal skin lesions scoring criteria of example 2.1 and the skin lesions score decrease index was calculated as in table 8.

TABLE 8 index of reduction in abdominal skin loss score for mice

Drop index%: (pre-dose score-post-dose score)/post-dose score 100.

As shown in Table 8, groups 3-8 showed different levels of reduction in abdominal skin loss in mice compared to the pruritus control group. The index of decrease in abdominal skin damage score of mice in groups 5 and 6 is higher than 80%, which indicates that flavor tablet 3 and flavor tablet 4 can effectively reduce abdominal skin damage of mice.

The experiments show that the flavor chips 3 and 4 can effectively reduce the pruritus frequency, are superior to the flavor chips 1 and 2 and the pet health control group, can effectively improve the abdominal skin damage phenomenon of mice, and are superior to the Aibo gram control group.

Example 3 formulation optimization and palatability evaluation

Multiple experiments show that the addition of the flavoring agent has no obvious influence on the functionality of the flavor tablet. In order to improve the palatability of the skin soothing flavor tablet for dogs, a flavoring agent needs to be screened. Microcrystalline cellulose between 30% and 70% w/w has no obvious effect on the palatability and functionality of the whole formula. The microcrystalline cellulose in the formulation was adjusted while ensuring 100% w/w of the total formulation. The eight formulations were prepared as described in example 1.2 to produce flavor chips 3.1, 3.2, 3.3, 3.4, 4.1, 4.2, 4.3, 4.4, and palatability evaluation was performed on the flavor chips, respectively, with the addition of flavoring agents based on formulations 3, 4, see table 9 for details.

TABLE 9 different flavor tablet formulations (w/w) of the flavor products

25 adult beagle dogs of physical health were screened for palatability evaluation. The palatability evaluation mode refers to a veterinary drug palatability demonstration guideline (Guideline on the demonstration of palatability of veterinary medicinal products), and during feeding of dogs, tablets are put into a food box and eaten within 2min to show the like; general eating is shown within 10 min; if the taste is greater than 10 minutes or the dogs do not eat the food, the dogs have no preference, and the acceptance rate of the dogs is more than or equal to 80 percent, namely the dogs have good palatability, and the palatability is evaluated according to the standard, and the results are shown in Table 10.

Table 10 table of dog palatability evaluation of different flavors for flavor tablets

Grouping	Xi Huan	In general	Dislike	Acceptance rate (like + general)
					Flavor tablet 3	16％	4％	80％	20％
Flavor tablet 3.1	40％	16％	44％	56％
					Flavor tablet 3.2	88％	4％	8％	92％
Flavor tablet 3.3	32％	24％	44％	56％
					Flavor tablet 3.4	52％	12％	36％	64％
Flavor tablet 4	12％	0	88％	12％
					Flavor tablet 4.1	32％	4％	64％	36％
Flavor tablet 4.2	70％	12％	18％	82％
					Flavor ofSheet 4.3	48％	8％	44％	56％
Flavor tablet 4.4	48％	28％	24％	76％

As shown in Table 10, the palatability acceptances of dogs to flavor chips 3.1-3.4 were all higher than those of flavor chip 3, the acceptances of dogs to flavor chip 3.2 were greater than 80%, and the acceptances of flavor chips 3.1, 3.2 and 3.3 were lower; the palatability acceptance rate of dogs to the flavor chips 4.1-4.4 is higher than that of the flavor chips 4, the acceptance rate of dogs to the flavor chips 4.2 is more than 80%, and the acceptance rates of the flavor chips 4.1, 4.2 and 4.3 are lower; the dogs were shown to prefer flavor chips 3.2 and 4.2.

In summary, according to the palatability evaluation result of dogs, dogs prefer flavor chips 3.2 and 4.2, and flavor chips 3.2 and 4.2 are selected for product stability test.

Example 4 product stability investigation

Stability studies were performed on 12 commercial packaged flavor chips with reference to the "health food stability test guidelines", wherein 3 flavor chips 3, 3 flavor chips 3.2, 3 flavor chips 4, and 3 flavor chips 4.2. The accelerated test should be carried out at 37+ -2deg.C under relative humidity RH 75+ -5% for 3 months without direct irradiation of light, and the accelerated test is carried out for 3 months for the appearance and moisture content change of the tablet, and the results are shown in Table 11 and Table 12.

Table 11 table for investigating appearance properties of flavor chips

As shown in Table 11, the appearance of the 12 batches of flavor chips was observed by visual inspection under natural light, and the results showed that the 3 batches of flavor chips 3 and 3 batches of flavor chips 3.2 were smooth on one surface, stable in properties and free from odor. 3 batches of flavor chips 4 samples were subjected to 3 months of accelerated test, and the 3 rd month had rough surface and darkened color. 3 batches of flavor chips 4.2 samples were subjected to 3 months of accelerated test, and the 2 nd month chip had rough surface, darkened color, and had off-flavor, and the 3 rd month chip had dull surface, further darkened color, and had off-flavor.

Table 12 moisture investigation table for flavor chips

As shown in Table 12, the water content of 12 batches of flavor chips was measured in accordance with the national standard "measurement of moisture in feed", and the measurement results showed that the water content of 3 batches of flavor chips 3 and 3 batches of flavor chips 3.2 was stable. 3 samples of flavor chips 4 and 3 samples of flavor chips 4.2 varied widely in moisture content.

In summary, after 3 months of accelerated stability investigation, the results show that: after 3 months of accelerated stability inspection, the flavor chips 4 and 4.2 have moisture absorption phenomenon, the moisture content is increased, and the properties are changed. The flavor slice 3 and the flavor slice 3.2 have no moisture absorption phenomenon and stable product quality. The final formulation was therefore set to formulation 3.2.

Example 5 clinical application of flavor tablet

5.1 clinical skin itch index scoring criteria for dogs

Through repeated experiments, the scratching times (the clinical phenomena are complex, the scratching times are replaced by the itching degree scores for facilitating the statistical analysis) and the skin lesions (the clinical phenomena are complex, the erythema phenomenon is the most prominent, and the itching degree scores are replaced by the skin lesion scores for facilitating the statistical analysis) are respectively corresponding to the itching feeling and the erythema degree. Since species changed from mice to dogs, the manner of evaluation was also changed. Clinical evaluation indexes and scoring standards of the skin soothing flavor tablets for dogs are determined and are shown in Table 13.

TABLE 13 criterion for scoring clinical skin itch index of dogs

5.2 evaluation of functionality

Adult pet dogs diagnosed with pruritus only were selected by a pet doctor and randomly divided into 5 groups, see table 14, group 4 pet health was purchased from pet information technology (Shanghai) limited, and group 5 ibok (3.6 mg) was purchased from the pastille askoli pharmaceutical factory, pyroitaly. Dogs were scored at 5.1 prior to treatment. The mode of administration and results after scoring are shown in tables 14 and 15.

TABLE 14 evaluation of canine erythema degree

Clinical decline index%: (pre-clinical score-post-clinical score)/post-clinical score 100.

As in table 14: the blank group gradually worsened, and the red rash levels of group 2, group 3, group 4 and group 5 were improved compared to the pre-treatment. The clinical score decrease index was more than 70% after 3d of group 2 and 3 administration, and both the clinical score decrease index and the effective rate were more than 80% after 14d of administration. In summary, the improvement of canine erythema in groups 2 and 3 was significantly better than groups 1, 4 and 5.

Table 15 table for evaluating the itching feeling of dogs

As in table 15: the blank group gradually worsened and the itching degree increased. The pruritus of group 2, group 3, group 4 and group 5 was improved compared to that before treatment. The clinical score decrease index was more than 70% after 4 hours of administration of group 2, group 3 and group 5, and the clinical score decrease index and the effective rate were both more than 80% after 7 days of administration. In summary, group 2, group 3 and group 5 significantly improved the dog itch feel over group 1, group 4.

In conclusion, the 3 groups of flavor tablets and the 3.2 groups of flavor tablets can effectively improve the itching feeling and the erythema degree of dogs, and the comprehensive efficacy is superior to that of the pet health group and the ibok group.

5.3 palatability evaluation

25 healthy adult pet dogs were screened and diagnosed by the pet doctor, and palatability evaluation was performed according to example 3, and the results are shown in table 16.

Table 16 palatability evaluation table

As shown in table 16, dogs had significantly higher palatability acceptances for group 2 than 80% over groups 1, 3 and 4, indicating that group 2 flavor chips had good palatability. In conclusion, the group 2 flavor chips have good palatability, and dogs are more willing to actively eat.

In conclusion, the flavor tablet 3.2 has good palatability, and dogs are more willing to actively eat.

The flavor tablet 3.2 can effectively improve canine skin diseases and has good palatability, and dogs are willing to actively eat, and the flavor tablet is superior to a pet health group and an ibok group in function and effect.

The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.

Claims

1. The skin soothing flavor tablet for dogs is characterized by comprising the following components in percentage by weight: 0.25 to 3.75 percent of cocklebur fruit extract, 0.25 to 3.75 percent of fructus cnidii extract, 1.5 to 2.0 percent of honeysuckle extract, 1.0 to 1.5 percent of Japanese thistle extract, 1.0 to 2.0 percent of herba schizonepetae extract, 0.25 to 4.25 percent of madder root extract, 1.5 to 3.05 percent of safflower extract, 0.75 to 3.15 percent of white nightshade extract and 0.1 to 1.0 percent of silicon dioxide, and the balance of microcrystalline cellulose.

2. The canine skin soothing flavor tablet of claim 1, wherein the tablet comprises the following components in weight percent: 3.25 to 3.75 percent of fructus xanthil extract, 3.25 to 3.75 percent of fructus cnidii extract, 1.75 percent of honeysuckle extract, 1.25 percent of herba seu radix Cirsii Japonici extract, 1.5 percent of herba schizonepetae extract, 1.25 to 4.25 percent of radix rubiae extract, 3.05 percent of safflower extract, 2.15 to 3.15 percent of white nightshade extract, 0.5 percent of silicon dioxide and the balance of microcrystalline cellulose.

3. The canine skin soothing flavor tablet of claim 2, wherein the tablet comprises the following components in weight percent:

4. A canine skin soothing flavor tablet according to any one of claims 1 to 3, further comprising 13% to 17% by weight of a flavouring agent, preferably 15%.

5. The canine skin soothing flavor tablet of claim 4, wherein the flavoring agent comprises at least one of chicken liver powder, hydrolyzed chicken liver powder, beef powder, and canine flavor enhancer.

6. The canine skin soothing flavor tablet of claim 5, wherein the flavoring agent is hydrolyzed chicken liver powder and/or a canine taste enhancer, preferably hydrolyzed chicken liver powder.

7. Use of a canine skin soothing flavor tablet of any one of claims 1 to 6 in the manufacture of a canine skin soothing medicament.

8. The use of claim 7, wherein skin relief comprises relief of itching and reduction of rash.

9. The method for preparing the canine skin soothing flavor tablet according to any one of claims 1 to 6, wherein the canine skin soothing flavor tablet is obtained by uniformly mixing the raw materials according to the proportion and tabletting.

10. A canine skin soothing drug comprising the canine skin soothing flavor tablet of any one of claims 1 to 6.