CN113456647A - Composition, preparation method and application thereof, preparation and application thereof - Google Patents

Composition, preparation method and application thereof, preparation and application thereof Download PDF

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CN113456647A
CN113456647A CN202110810784.4A CN202110810784A CN113456647A CN 113456647 A CN113456647 A CN 113456647A CN 202110810784 A CN202110810784 A CN 202110810784A CN 113456647 A CN113456647 A CN 113456647A
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丁睿
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Beijing Zhongke Haoying Biotechnology Co ltd
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    • A23K50/40Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4525Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis

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Abstract

The application relates to the technical field of pet foods, and particularly discloses a composition, a preparation method and application thereof, and a preparation and application thereof. The composition comprises the following pharmacologically acceptable raw material components: curcumin, resveratrol, piperine, astaxanthin and boswellic acid; the preparation method of the composition comprises mixing the above raw materials uniformly; the preparation comprises the composition and a pharmacologically acceptable carrier and/or additive and/or feed raw material; the composition or the preparation can be applied to medicines, foods and/or health products for treating joint diseases of pets. The pet bone joint disease treatment device can treat the pet bone joint disease, so that the life quality of the pet is improved.

Description

Composition, preparation method and application thereof, preparation and application thereof
Technical Field
The application relates to the technical field of pet foods, in particular to a composition, a preparation method and application thereof, and a preparation and application thereof.
Background
Osteoarthritis is a synovial joint disease, which is manifested by deterioration and loss of articular cartilage, accompanied by changes in the structure and function of the entire joint, including the synovium, meniscus (knee), periarticular ligaments, and subchondral bone. The causes of osteoarthritis have long been considered to be the result of aging or trauma, but as people become increasingly aware, the causes of osteoarthritis are now considered to be diverse.
Pathological studies of osteoarthritis indicate that the presence of inflammatory mediators at joints is directly linked to osteoarthritis, among which the major inflammatory mediators are tumor necrosis factor-alpha (TNF- α) and interleukin 1 β (IL-1 β), which are secreted mainly by chondrocytes, monocytes, osteoblasts and synovial tissue. It has been found that TNF-alpha and IL-1 beta are present in elevated levels in synovial fluid, synovial membrane membranes, subchondral bone and cartilage in patients with osteoarthritis.
In one aspect, TNF- α and IL-1 β can induce joint cells to release pro-inflammatory cytokines (e.g., IL-6) and pro-inflammatory chemokines (e.g., IL-8) to exacerbate and perpetuate osteoarthritis symptoms. Under the action of these cytokines or chemokines, chondrocytes are able to up-regulate the expression of genes encoding Inducible Nitric Oxide Synthase (iNOS), cyclooxygenase 2(COX-2), and prostaglandin E synthase (mPGES), thereby promoting the release of Nitric Oxide (NO) and prostaglandin E2(PGE 2). NO and PGE2 enhance the production and activity of proteolytic enzymes, for example, NO and PGE2 enhance the production of Matrix Metalloproteinases (MMPs), thereby inhibiting proteoglycan synthesis by chondrocytes and down-regulating the synthesis of major extracellular matrix (ECM, highly cross-linked triple helical type II collagen) components, thereby causing joint damage and promoting the production of joint inflammation. Among them, MMP-1, MMP-3 and MMP-13 are key regulators of cartilage destruction.
On the other hand, TNF- α and IL-1 β are capable of inducing the production of Reactive Oxygen Species (ROS), producing free radicals, which lead to the damage and degeneration of cartilage; meanwhile, TNF-alpha and IL-1 beta can also reduce the gene expression of antioxidant enzymes (including superoxide dismutase, catalase and glutathione peroxidase), weaken the scavenging effect on free radicals and further increase the damage and degeneration of ROS on cartilage.
At present, the main drugs for treating osteoarthropathy comprise the following drugs:
non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, naproxen, etc., that reduce the inflammatory response (fever, pain, etc.) by inhibiting the activity of cyclooxygenase (COX-1, COX-2) and reducing the production of PGE2, but that are potentially at risk of causing other diseases, such as gastrointestinal, renal, and cardiovascular diseases;
TNF- α antagonists such as Adalimumab (Adalimumab), infliximab (infliximab), which can reduce the effect of TNF- α on inflammation by specifically binding to TNF- α, need to be administered by injection, and are at risk of causing various adverse reactions such as infection, neurodegeneration, anaphylaxis, immunosuppression, malignant diseases, and abnormal lymphocyte proliferation;
IL-1 antagonists, such as anakinra, which block the biological activity of IL-1 by competitively inhibiting the binding of IL-1 to its receptor, also require administration by injection and are potentially at risk of causing headache, nausea, diarrhea, abdominal pain.
Disclosure of Invention
In order to improve the treatment means and treatment effect on joint diseases of pets and improve the life quality of pets, the application provides a composition, a preparation method and application thereof, a preparation and application thereof.
In a first aspect, the present application provides a composition, using the following technical solutions:
a composition comprising pharmacologically acceptable raw material components of: curcumin, resveratrol, piperine, astaxanthin and boswellic acid.
Preferably, the curcumin is an extract of dried rhizome of Curcuma longa L belonging to Zingiberaceae family.
Preferably, the resveratrol may be extract of dried rhizome and/or root of Polygonum cuspidatum (Polygonum cuspidatum Sieb. et Zucc.) and/or extract of pericarp of Vitis vinifera (Vitis vinifera.) belonging to Polygonaceae.
Preferably, the piperine may be an extract of dried near-ripe or ripe fruit of pepper (Piper nigrum L.) of the family piperiaceae.
Preferably, the astaxanthin may be selected from Haematococcus pluvialis, and/or Phaffia rhodozyma, and/or krill oil.
Preferably, the boswellic acid may be boswellic extract of resin exuded from bark of Boswellia serrata (Boswellia carterii Birdw.) and plants of the same genus (Boswellia bhaw-dajiana Birdw.).
By adopting the technical scheme, the composition comprises curcumin, resveratrol, piperine, astaxanthin and boswellic acid. The composition can weaken the damage of free radicals to chondrocytes by inhibiting the gene expression of TNF-alpha and IL-1 beta, has the functions of relieving pain, eliminating inflammation and recovering cartilage better, realizes the treatment of the osteoarticular diseases of pets, and further improves the life quality of the pets. Meanwhile, the composition can also be applied to medicines, foods and health-care products for treating joint diseases of pets.
The NF-kB signaling pathway regulates the expression of a variety of genes involved in inflammatory responses, including TNF- α and IL-1 β. In synovial cells with osteoarthritis, the NF-kB signaling pathway can be found to be activated, thereby inducing the expression of pro-inflammatory genes, such as TNF- α, IL-1 β, MMP-1, MMP-3, and COX-2. Curcumin can reduce the activation state of the NF-kB signaling pathway through a variety of pathways, thereby inhibiting gene expression of TNF. Resveratrol is a potent non-cell specific inhibitor of NF-kB activation. Curcumin and resveratrol can inhibit NF-kB activation to inhibit COX-2 activity and reduce PGE2 production, thereby exhibiting anti-inflammatory and analgesic effects.
In addition, piperine enhances the bioavailability of drugs by affecting enzymes responsible for drug metabolism, blood supply to gastrointestinal cells, and cell membrane fluidity, enhancing drug transport. The piperine can be added to remarkably improve the bioavailability of curcumin and resveratrol.
The astaxanthin has unique structures of hydrophilicity and lipophilicity, can be positioned in cell membranes and cytoplasm at the same time, has a conjugated double bond structure which is a good electron donor, can convert free radicals into more stable substances, can regulate the gene expression of antioxidant enzyme by TNF-alpha and IL-1 beta in inflammatory reaction, and can make up the deficiency of the antioxidant enzyme by taking the astaxanthin as a strong oxidant, play a role in removing the free radicals and weaken the damage of active oxygen to cartilage.
5-lipoxygenase (5-LO) produces inflammatory leukotrienes, which cause inflammation by promoting free radical damage, calcium translocation, cell adhesion and inflammatory cell migration to inflamed body areas, and boswellic acid inhibits its synthesis and, in addition, has analgesic effect.
Therefore, the composition provided by the application can effectively treat joint diseases of pets, relieve the pain of the pets and improve the life quality of the pets.
Preferably, the raw material components have the following weight percentages:
30.0-90.0% of curcumin;
resveratrol 2.0-66.0%;
0.16 to 3.0 percent of piperine;
3.0% -67.0% of astaxanthin;
0.1 to 35.0 percent of boswellic acid.
In a particular embodiment, curcumin may be 31.5%, 36.4%, 46.6%, 56.5% or 61.4%.
In a particular embodiment, curcumin may also be 30-31.5%; 30 to 36.4 percent; 30 to 46.6 percent; 30 to 56.5 percent; 30-61.4%; 31.5 to 36.4 percent; 31.5 to 46.6 percent; 31.5 to 56.5 percent; 31.5 to 61.4 percent; 31.5 to 90 percent; 36.4-46.6%; 36.4-56.5%; 36.4-61.4%; 36.4-90%; 46.6 to 56.5 percent; 46.6 to 61.4 percent; 46.6 to 90 percent; 56.5 to 61.4 percent; 56.5-90% or 61.4% -90%.
In a particular embodiment, the resveratrol may be 6.0%, 7.2%, 10.84%, 12.6%, 15.25% or 20.4%.
In a particular embodiment, resveratrol may also be 2-6.0%; 2 to 7.2 percent; 2 to 10.84 percent; 2 to 12.6 percent; 2 to 15.25 percent; 2 to 20.4 percent; 6.0 to 7.2 percent; 6.0 to 10.84 percent;
6.0 to 12.6 percent; 6.0 to 15.25 percent; 6.0 to 20.4 percent; 6.0 to 66 percent; 7.2-10.84%; 7.2-12.6%; 7.2-15.25%; 7.2-20.4%; 7.2-66%; 10.84-12.6%; 10.84-15.25%; 10.84-20.4%; 10.84-66%; 12.6 to 15.25 percent; 12.6 to 20.4 percent; 12.6 to 66 percent; 15.25 to 20.4 percent; 15.25-66% or 20.4-66%.
In a particular embodiment, piperine may be 0.4%, 0.76%, 1.5% or 2.5%.
In a particular embodiment, piperine may also be 0.16-0.4%; 0.16-0.76%; 0.16-1.5%; 0.16-2.5%; 0.4-0.76%; 0.4-1.5%; 0.4-2.5%; 0.4 to 3.0 percent; 0.76 to 1.5 percent; 0.76 to 2.5 percent; 0.76 to 3.0 percent; 1.5 to 2.5 percent; 1.5-3.0% or 2.5-3.0%.
In a particular embodiment, the astaxanthin may be 13.8%, 17.71%, 33.8% or 40.2%.
In a particular embodiment, the astaxanthin may also be 3.0-13.8%; 3.0 to 17.71 percent; 3.0 to 33.8 percent; 3.0 to 40.2 percent; 13.8 to 17.71 percent; 13.8 to 33.8 percent; 13.8 to 40.2 percent; 13.8 to 67.0 percent; 17.71 to 33.8 percent; 17.71 to 40.2 percent; 17.71 to 67.0 percent; 33.8 to 40.2 percent; 33.8 to 67.0 percent or 40.2 to 67.0 percent.
In a particular embodiment, the boswellic acid may be 5.0%, 10.5%, 17%, 24% or 28%.
In a particular embodiment, the boswellic acid may also be 0.1-5.0%; 0.1 to 10.5 percent; 0.1 to 17 percent; 0.1-24%; 0.1-28%; 5.0 to 10.5 percent; 5.0 to 17 percent; 5.0 to 24 percent; 5.0 to 28 percent; 5.0 to 35.0 percent; 10.5 to 17 percent; 10.5 to 24 percent; 10.5 to 28 percent; 10.5 to 35.0 percent; 17 to 24 percent; 17 to 28 percent; 17 to 35.0 percent; 24 to 28 percent; 24-35.0% or 28-35.0%.
By adopting the technical scheme, through experimental analysis, when the raw material components in the composition are controlled within the range, the free radical removal capability of the composition can be further improved, so that the functions of relieving pain, eliminating inflammation and recovering cartilage can be better achieved, the treatment on joint diseases of pets is improved, the pain of the pets is relieved, and the life quality of the pets is improved.
Preferably, the ratio of the total addition amount of the curcumin and the resveratrol to the addition amount of the piperine is 10: (0.05-0.3).
By adopting the technical scheme, through experimental analysis, when the ratio of the total addition amount of the curcumin and the resveratrol to the addition amount of the piperine in the composition is controlled within the range, the bioavailability of the composition can be further improved, and further inflammation can be better inhibited, so that the treatment of joint diseases of pets by the composition is further improved.
Preferably, the curcumin accounts for 30.0 to 60.0 percent by weight.
Preferably, the weight percentage of the piperine is 0.65-1.5%.
By adopting the technical scheme, on the basis of controlling the ratio of the total adding amount of the curcumin and the resveratrol to the adding amount of the piperine in the composition within the range, the adding amounts of the curcumin and the astaxanthin are further controlled to be 30.0-60.0% and 0.65-1.5% respectively, and the treatment effect of the composition on the joint diseases of pets can be further effectively improved.
Preferably, the composition further comprises one or more of vitamins, amino acids, minerals.
In a specific embodiment, the vitamin may be any one or more of vitamin a, vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B6, niacin, pantothenic acid, folic acid, biotin, choline, vitamin C.
In a particular embodiment, the amino acid may be any one or more of alanine, arginine, asparagine, aspartic acid, citrulline, cysteine, glutamic acid, glutamine, glycine, histidine hydroxyproline, hydroxyserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, valine, HICA (α -hydroxyisocaproic acid), HIVA (α -hydroxyisovaleric acid), HIMVA (α -hydroxymethylvaleric acid).
In a particular embodiment, the mineral may be any one or more of sodium, potassium, calcium, phosphorus, magnesium, chloride, iron, zinc, copper, manganese, selenium, iodide.
By adopting the technical scheme, any one of the vitamins, amino acids and/or minerals can be added into the composition, so that the composition can be used for treating joint diseases of pets, and simultaneously, the vitamins, amino acids and/or minerals can be supplemented for the pets, thereby further improving the immunity and vitality of the pets and further promoting the treatment of the joint diseases of the pets.
In a second aspect, the present application provides a method for preparing a composition, which adopts the following technical scheme:
a preparation method of the composition, which is to uniformly mix any one of the raw material components.
In a third aspect, the present application provides a formulation, using the following technical scheme:
a preparation comprises the composition and a pharmacologically acceptable carrier and/or additive and/or feed raw material.
In a particular embodiment, the carrier and/or additive and/or feedstuff can be one or more of maltodextrin, pregelatinized corn starch, microcrystalline cellulose, silicon dioxide, glucose, white granulated sugar, salt, erythritol, sucralose, citric acid, chondroitin sulfate, animal protein hydrolysate (powder), animal (vegetable) oil, fish meal, chicken oil, soybean meal and beet pulp.
Preferably, the preparation is tablets, syrups, capsules, granules, powder or injections.
By adopting the technical scheme, the composition can be prepared into a preparation by being matched with a pharmacologically acceptable carrier and/or additive and/or feed raw materials on the basis of the composition. The joint disease of pets can be treated by acting on pets with the preparation.
In a fourth aspect, the present application provides the use of the above composition or the above formulation in a medicament, food and/or health product for treating joint diseases in pets.
By adopting the technical scheme, the composition and the preparation prepared from the composition can be used in medicines, foods and health products, and can be used for treating joint diseases of pets.
In summary, the present application has the following beneficial effects:
the composition can weaken the damage of free radicals to chondrocytes, play a better role in relieving pain, eliminating inflammation and recovering cartilage by inhibiting the gene expression of TNF-alpha and IL-1 beta, and realize the treatment of osteoarticular diseases of pets, thereby improving the life quality of pets.
The application also provides a preparation prepared by using the composition and matching with a pharmacologically acceptable carrier and/or additive and/or feed raw material. The joint disease of pets can be treated by acting on pets with the preparation.
Drawings
FIG. 1 shows the results of the clinical tests one of the tests of the present application.
Detailed Description
The present application provides a composition comprising the following pharmacologically acceptable raw material components: curcumin, resveratrol, piperine, astaxanthin and boswellic acid. The weight percentage is as follows: 30.0-90.0% of curcumin; resveratrol 2.0-66.0%; piperine 0.16% -2.7%; 3.0% -67.0% of astaxanthin; 1.0 to 35.0 percent of boswellic acid.
Further, the ratio of the total adding amount of the curcumin and the resveratrol to the adding amount of the piperine is 10: (0.05-0.3). Still further, the weight percentage of curcumin may be 30.0-60.0%. The piperine may be present in an amount of 0.65-1.5% by weight. In addition, the composition also contains one or more of vitamins, amino acids, and minerals. The application also provides a preparation method of the composition, namely, raw material components of the composition are uniformly mixed. The composition can be used in medicines, foods and/or health products for treating joint diseases of pets.
The application also provides a preparation which comprises the composition and a pharmacologically acceptable carrier and/or additive and/or feed raw material. The preparation is tablet, ointment, syrup, capsule, granule, powder or injection. The preparation can be used in medicines, foods and/or health products for treating joint diseases of pets.
The raw materials, reagents, solvents and other test materials used in the following preparation examples and examples were all commercially available.
The present application is described in further detail below with reference to preparation examples 1 to 12, examples 1 to 13, and the detection test.
Preparation example
Preparation examples 1 to 12
Preparation examples 1-12 each provide a composition, and the above preparation examples differ in the weight percentages of the raw material components in the composition, as shown in table 1.
The preparation method of the tissue comprises the following steps: the compositions corresponding to the respective preparation examples were prepared by thoroughly and uniformly mixing the raw material components shown in table 1, respectively.
TABLE 1 raw material Components of preparation examples 1 to 12
Figure BDA0003167113930000111
Examples
Examples 1 to 12
Examples 1-12 provide formulations made using the compositions prepared in preparative examples 1-12, respectively. The only difference is in the composition used. The preparation is a tablet, wherein the composition and other raw material components are shown in table 2.
Table 2 raw material components of the formulations of examples 1-12
Raw material components Examples
Composition (g) 18.82
Microcrystalline cellulose (g) 28.00
Predextrinization corn starch (g) 18.00
Magnesium stearate (g) 10.00
Chicken liver powder (g) 15.18
Silicon dioxide (g) 10.00
Total amount (g) 100
The preparation method of the preparation comprises the following steps:
(1) weighing the raw materials according to the raw material components shown in Table 2;
(2) putting the above raw materials into a V-shaped powder mixer (model V-3B), mixing for 20min by using the V-shaped powder mixer to obtain a uniformly mixed mixture, and taking out the mixture from the V-shaped powder mixer;
(3) the mixture was compressed using a laboratory single punch press (model TDP-5T) to control the weight of each tablet to 0.5g, thereby obtaining tablets of 0.5 g/tablet.
The tablets prepared in examples 1-12 were fed to pet dogs at a dose of 0.5g per 5kg body weight per day.
Example 13
This example provides a formulation made using the composition prepared in preparation example 11. The composition and other raw material components of the preparation are shown in table 3.
Table 3 raw material components of the formulation of example 13
Figure BDA0003167113930000121
Figure BDA0003167113930000131
The preparation method of the preparation comprises the following steps:
(1) weighing the raw materials according to the raw material components shown in Table 3;
(2) putting the composition, microcrystalline cellulose, maltodextrin, chicken liver powder and sodium tripolyphosphate in a V-shaped powder mixer (model V-3B), mixing for 20min by using the V-shaped powder mixer to obtain a uniformly mixed mixture, and taking out the mixture from the V-shaped powder mixer;
(3) putting the mixture obtained in the step (2) into a stainless steel container, slowly adding the fish oil, and stirring by using a stainless steel stirring rod while adding; and after the fish oil is completely added, continuously stirring for 15min to obtain a viscous paste.
The cream prepared in example 13 was fed to pet cats at a dose of 1g per 1kg body weight per day.
Detection test
Safety test
This example was conducted to test the safety of the compositions prepared in the above preparation examples 1 to 12. The test object is an SD rat, and the test contents are as follows:
1. oral acute toxicity test
Test number: 12 groups of SD rats, 10 rats each group; each group corresponds to the composition prepared in one preparation example;
the test contents are as follows: performing oral acute toxicity experiments on SD rats, wherein the experimental standard is GB/T15193.3-2003;
observing whether SD rats have abnormal responses, such as shrugging, lying down, pale concha or hyperemia, exophthalmos, teetering, muscle paralysis, dyspnea, coma, convulsion, incontinence of urine and feces; whether there is death and the cause of death are analyzed.
2. Feeding test
Test number: 12 groups of SD rats, 10 rats each group; each group corresponds to the composition prepared in one preparation example;
the test contents are as follows: SD rats are subjected to a 30-day feeding test (short-term oral toxicity test, subacute toxicity test) with the test standard reference GB/T23179-2008;
observing the growth condition, weight and food utilization rate of SD rat, observing hematology and blood biochemical index, performing autopsy to observe pathological changes of stomach and intestine, and measuring viscera coefficient values of liver, kidney, spleen, testis (male) and ovary (female).
And (3) test results: all SD rats tested have no abnormal phenomena in the test 1, and have good growth and development, normal behavior, mental status, hair color, food intake, drinking water and excrement, which shows that the compositions prepared by the preparation examples 1-12 of the application have no adverse effect on the general conditions of the rats, the weight increase and growth and development of the rats, and the food utilization rate, the basic indexes of hematology, the main indexes of blood biochemistry and the main organs of the rats.
The results show that the components prepared by the method have no acute toxic or side effect, and the long-term feeding of the components can be presumed to have no adverse effect on the weight gain, growth and development, food utilization rate, basic indexes of hematology, main indexes of blood biochemistry and main organs of animals.
Second, clinical trial one
Clinical trials were conducted using the formulations prepared in examples 1-12. The formulations prepared in examples 1-12 are numbered 1-12, respectively.
Test site: a pet fostering and nursing center.
Test subjects: 12 pet dogs, wherein 5 male dogs and 7 female dogs are selected; the age is 7-8 years, and the average age is 7.5 years; the body weight varies from 8kg to 36 kg. The test dogs participating in the test are all dogs with joint diseases which are diagnosed according to X-ray films; and during the test period, the dogs were only raised individually in a 1m x 1m kennel, the height of which allowed the dogs to stand freely and lie. All the dog house floors are paved with cushions with the same thickness, and the temperature of the dog house is the same.
Study and rest of test dogs: the dogs are respectively and independently taken out in the morning and at the evening in sequence, the dogs are drawn by the same breeder to walk in a courtyard, the walking time is 30min, and the dogs are kept in a dog house in the rest time. All dogs were fed the same food and water without any health products and drugs.
The test method comprises the following steps: the formulations prepared in examples 1 to 12 were randomly distributed to 12 test dogs, respectively, and the corresponding doses of the formulations were mixed into food and fed to the dogs in accordance with the feeding dose of 0.5g of the formulations per 5kg of body weight ingested per day, based on the body weight of the dogs. The test period is 30 days, and the work and rest of the test dog are unchanged in the test period.
The detection method comprises the following steps:
(1) the initial length of walking and the number of active rests (morning and evening) were recorded for each dog on day 7 before the start of the trial, and the average of day 7 was taken as the base.
Initial walking time: within 30min, the time from leaving the dog house until the dog actively takes a rest (stands still in place or lies on the stomach) for the first time due to joint diseases.
Number of active rests: within 30min, dogs had active rest only for joint disease.
(2) During the test period, the initial walking length and the number of active rest times (once in the morning and once in the evening) of each test dog were recorded on days 15 and 30, respectively, and the average value of each day was recorded and taken as the test result. The test results are shown in table 4.
TABLE 4 results of clinical trials I
Figure BDA0003167113930000161
As can be seen from fig. 1 and table 4, the formulations prepared in examples 1 to 12 had good alleviation and improvement effects on joint diseases of pet dogs in addition to example 5. Therefore, the ratio of the added amounts of curcumin and resveratrol to the added amount of piperine is 10: (0.05-0.3) the composition can be used for preparing preparations which can effectively relieve and improve the joint diseases of test dogs. Since the ratio of the added amounts of curcumin and resveratrol to the added amount of piperine in the formulation prepared in example 5 was 10: 0.04, the ratio is less than 10: (0.05-0.3), so the preparation prepared in example 5 has less improvement effect on the symptoms of joint diseases of test dogs. In addition, the ratio of the added amounts of curcumin and resveratrol to the added amount of piperine in the composition utilized in the preparation of the formulation of example 4 was 10: 0.34, the ratio is greater than 10: (0.05-0.3), the ratio of the added amount of the curcumin and the resveratrol to the added amount of the piperine in the composition is 10: the test effect of (0.05 to 0.3) was not significantly improved in example 4. Therefore, based on double consideration of cost and effect, the ratio of the added amount of the curcumin and the resveratrol to the added amount of the piperine in the composition is controlled to be 10: preferably (0.05-0.3).
Third, clinical trial two
Clinical trials were conducted using the formulation prepared in example 11.
Test subjects: 8 spontaneously arthritic dogs with body weights varying from 2.8kg to 40 kg. Before participating in the test, clinical manifestations such as lameness, difficulty in getting up, leg limping, etc. were observed. Dogs were asked to discontinue any medications or other health care products from 14 days prior to participation in clinical testing to the end of clinical testing.
The canine panelists involved in the test were required to observe the clinical condition of the dogs during their clinical trials and to record once every 7 days before and at the time of the test. The results of each observation were scored according to the dimensions and scoring criteria shown in table 5.
And (3) test period: for 35 days.
The test method comprises the following steps: throughout the test period, the canine subjects were fed dogs with meals at a dose of 0.5g per 5kg body weight (0.25 g for 2.5kg body weight). And recorded for canine cases before the start of the test and on days 7, 14, 21, 28, and 35 after the start of the test, respectively. The test results are shown in table 6.
TABLE 5 clinical trial Scoring criteria
Figure BDA0003167113930000181
Figure BDA0003167113930000191
TABLE 6 results of clinical trials II
Figure BDA0003167113930000192
Figure BDA0003167113930000201
As can be seen from the above test tests, the formulation prepared using the composition provided herein provides great relief from pain in dogs caused by osteoarthritis from the beginning of the test to the end of the test when the formulation is fed to pets. The preparation prepared from the composition has a good effect on treating joint diseases of pets, can improve the condition of the joint diseases of the pets in a short time, improves the life quality of the pets, and reduces the pain of the pets caused by the joint diseases.
The present embodiment is only for explaining the present application, and it is not limited to the present application, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present application.

Claims (10)

1. A composition comprising pharmacologically acceptable raw material components of: curcumin, resveratrol, piperine, astaxanthin and boswellic acid.
2. The composition of claim 1, wherein the raw material components comprise, by weight:
30.0-90.0% of curcumin;
resveratrol 2.0-66.0%;
0.16 to 3.0 percent of piperine;
3.0% -67.0% of astaxanthin;
0.1 to 35.0 percent of boswellic acid.
3. The composition as claimed in claim 2, wherein the ratio of the total amount of curcumin and resveratrol added to the amount of piperine added is 10: (0.05-0.3).
4. A composition according to claim 2, wherein the curcumin is present in an amount of 30.0 to 60.0% by weight.
5. A composition according to claim 2, wherein the piperine is present in an amount of 0.65 to 1.5% by weight.
6. The composition of claim 1, wherein the composition further comprises one or more of vitamins, amino acids, and minerals.
7. A method for preparing a composition, comprising mixing the raw material components of any one of claims 1 to 6.
8. A formulation comprising a composition according to any one of claims 1 to 6 together with a pharmacologically acceptable carrier and/or additive and/or feedstuff.
9. A formulation according to claim 8, wherein the formulation is a tablet, ointment, syrup, capsule, granule, powder or injection.
10. Use of a composition according to any one of claims 1 to 6 or a formulation according to claim 8 in a medicament, food and/or health product for the treatment of joint disorders in pets.
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CN110740743A (en) * 2017-06-09 2020-01-31 司斐股份有限公司 Composition for treating retinal diseases
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US20040037903A1 (en) * 2001-06-13 2004-02-26 Lemmo Edward A. Phytonutrient formula for the relief of chronic pain resulting from inflammation
US20080020998A1 (en) * 2006-07-24 2008-01-24 Muhammed Majeed Sustained release compositions for the therapeutic management of pain, inflammation and inflammation-associated disorders and prophylactic/ therapeutic methods thereof
CN110740743A (en) * 2017-06-09 2020-01-31 司斐股份有限公司 Composition for treating retinal diseases
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