CN115282248A - Composition for relieving joint pain or treating arthritis, and preparation method and application thereof - Google Patents
Composition for relieving joint pain or treating arthritis, and preparation method and application thereof Download PDFInfo
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- CN115282248A CN115282248A CN202210973824.1A CN202210973824A CN115282248A CN 115282248 A CN115282248 A CN 115282248A CN 202210973824 A CN202210973824 A CN 202210973824A CN 115282248 A CN115282248 A CN 115282248A
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Abstract
The invention provides a composition for relieving joint pain or treating arthritis, and a preparation method and application thereof, wherein the composition comprises the following components: bone-strengthening component, protecting component, calcium agent, turmeric and natto; wherein the bone fixing component comprises at least one of non-denatured type II collagen and eggshell membrane extract; the protective component comprises at least one of hyaluronic acid, sodium hyaluronate and calcium hyaluronate; the calcium agent comprises at least one of calcium lactate, calcium carbonate and calcium gluconate. The components in the composition have synergistic effect, and the combined application of the components can reduce inflammation, so that the joint pain of a patient is reduced, the repair of joint cartilage is promoted, the joint function is improved, the joint cartilage is prevented from being further degenerated and changed, and adverse reactions such as gastrointestinal discomfort, diarrhea and the like are not observed, thereby proving that the composition provided by the invention is safe and effective.
Description
Technical Field
The invention relates to the technical field of a composition for relieving joint pain or treating arthritis, and particularly relates to a composition for relieving joint pain or treating arthritis, and a preparation method and application thereof.
Background
The pathological mechanism of osteoarthritis is mainly characterized by degeneration and destruction of articular cartilage, apoptosis of chondrocytes, subchondral bone sclerosis or cystic change, narrowing of joint space and the like, and is clinically manifested by joint pain, morning stiffness, dyskinesia and the like. The pathological mechanism of arthritis is not clear, and the major risk factors include age, obesity, excessive exercise, trauma, and the like.
At present, the drugs for treating arthritis mainly comprise nonsteroidal anti-inflammatory drugs, glucocorticoids, glucosamine, cytotoxic drugs, adrenocortical hormone, antibiotics and the like. Although the western medicines have obvious curative effects, the western medicines also have great side effects. For example, nonsteroidal anti-inflammatory drugs, while relieving fever and pain, may also damage the gastrointestinal mucosa, manifested as punctate bleeding, diffuse superficial mucosal erosion, and may also cause local ulcers, massive bleeding and even perforation. In addition, adverse reactions may occur in the liver, nervous system, urinary system, cardiovascular system of blood system, etc.
Besides the medicines, there are many nutritional supplements for improving arthritis, such as chondroitin sulfate, glucosamine, chondroitin sulfate, frankincense, turmeric, fish oil and the like, but the action effect of these dietary supplements is limited, and there is a big controversy, especially for the effect of glucosamine and chondroitin sulfate on improving arthritis, and the opinions of many scholars are not uniform.
A large number of clinical studies at home and abroad in recent years show that the hyaluronic acid injection into the joint cavity has obvious effect on treating arthritis, and has no serious side effect, safety and reliability. Arthritis is a long-term chronic disease, the jointThe hyaluronic acid is injected in the cavity, although the curative effect is remarkable, the injection skill is extremely high, and the patient needs to endure more severe pain. Meanwhile, long-term dependence on the supplement of exogenous high-concentration hyaluronic acid can inhibit the secretion of synovial cells, break the balance of the environment in joint cavities and possibly cause further deterioration of the disease. In recent years, foreign research reports have shown that isotopes are used 14 About 8.8% of hyaluronic acid is absorbed in vivo after 7 days of continuous administration of C-labeled hyaluronic acid, which breaks the conventional idea that hyaluronic acid is not absorbed as a macromolecule, but has limited effect of treating arthritis by oral administration of hyaluronic acid because the oral absorption of hyaluronic acid is only 8.8%.
Disclosure of Invention
In view of the above, the present invention provides a composition for relieving joint pain or treating arthritis, wherein the components in the composition have synergistic effects, and the composition has the effects of quickly relieving joint pain or treating arthritis, and is safe and free of side effects.
In order to solve the technical problems, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a composition for relieving joint pain or treating arthritis, the composition comprising the following components: bone-strengthening component, protecting component, calcium agent, turmeric and natto;
wherein the bone fixing component comprises at least one of non-denatured type II collagen and eggshell membrane extract; the protective component comprises at least one of hyaluronic acid, sodium hyaluronate and calcium hyaluronate; the calcium agent comprises at least one of calcium lactate, calcium carbonate and calcium gluconate.
Further, the composition comprises the following components in percentage by mass: bone strengthening components: a protective component: calcium agent: turmeric: natto = (10-50): (0.1-5): (30-150): (20 to 100): (5-50).
Further, the composition comprises the following components in percentage by mass: bone strengthening components: a protective component: calcium agent: turmeric: natto =20:1:90:60:20.
further, the preparation method of the eggshell membrane extract comprises the following steps: treating the eggshell membrane by physical, chemical or enzymatic methods to form the eggshell membrane into a soluble polypeptide mixture; wherein, the physical method comprises pressurization and heating; the chemical processes include acid-base treatment, reduction, and oxidation.
Further, the composition also comprises one or more pharmaceutically acceptable excipients.
Further, the pharmaceutically acceptable excipients include fillers, lubricants, binders; wherein the filler comprises at least one of microcrystalline cellulose, isomaltulose, calcium hydrogen phosphate, calcium carbonate; the lubricant comprises at least one of magnesium stearate, stearic acid, zinc stearate, calcium stearate, talcum powder and superfine silica gel powder; the adhesive comprises at least one of methylcellulose, hydroxypropyl methylcellulose, sodium hydroxymethyl cellulose and ethyl cellulose.
Further, the mass ratio of the bone-fixing component to the pharmaceutically acceptable excipient in the composition is (10-50): (150 to 220).
In a second aspect, the present invention provides a process for preparing a composition as described above, said process comprising: mixing the bone-strengthening component, the protective component, the calcium agent, the turmeric and the natto, and granulating to obtain the composition.
Further, the composition also comprises a filler, a lubricant and a binder, and the preparation method comprises the following steps: mixing the calcium agent, the turmeric, the natto, the filler and the adhesive, and performing wet granulation and drying to obtain powder A; mixing the bone fixing component, the protective component, the lubricant and the filler with the powder A to obtain the composition;
wherein the filler comprises at least one of microcrystalline cellulose, isomaltulose, calcium hydrogen phosphate, and calcium carbonate; the lubricant comprises at least one of magnesium stearate, stearic acid, zinc stearate, calcium stearate, talcum powder and superfine silica powder; the adhesive comprises at least one of methylcellulose, hydroxypropyl methylcellulose, sodium hydroxymethyl cellulose and ethyl cellulose.
In a third aspect, the present invention provides the use of a composition as described above for the manufacture of a medicament for the treatment of joint pain or arthritis.
Further, the dosage forms of the medicine comprise tablets, capsules and powder.
The technical scheme of the invention has the following beneficial effects:
the invention provides a composition for relieving joint pain or treating arthritis, and a preparation method and application thereof, wherein the composition comprises the following components: bone-strengthening component, protecting component, calcium agent, turmeric and natto; wherein the bone fixing component comprises at least one of non-denatured type II collagen and eggshell membrane extract; the protective component comprises at least one of hyaluronic acid, sodium hyaluronate and calcium hyaluronate; the calcium agent comprises at least one of calcium lactate, calcium carbonate and calcium gluconate. The components in the composition have synergistic effect, and the combined application of the components can reduce the inflammation of a mouse, so that the joint pain of a patient is reduced, the repair of joint cartilage is promoted, the joint function is improved, the joint cartilage is prevented from being further degenerated and changed, and adverse reactions such as gastrointestinal discomfort, diarrhea and the like are not observed, thereby proving that the composition provided by the invention is safe and effective.
Detailed Description
For a further understanding of the invention, reference will now be made to the preferred embodiments of the invention in conjunction with the following examples, but it will be understood that the description is intended to illustrate the features and advantages of the invention further, and not to limit the invention.
In a first aspect, the present invention provides a composition for relieving joint pain or treating arthritis, the composition comprising the following components: bone-strengthening component, protecting component, calcium agent, turmeric and natto; wherein the bone fixing component comprises at least one of non-denatured type II collagen and eggshell membrane extract; the protective component comprises at least one of hyaluronic acid, sodium hyaluronate and calcium hyaluronate; the calcium agent comprises at least one of calcium lactate, calcium carbonate and calcium gluconate.
The invention provides a composition for relieving joint pain or treating arthritis, which comprises the following effective components: bone strengthening component, protecting component, calcium agent, turmeric and natto.
Specifically, the bone fixing component comprises at least one of non-denatured type II collagen and eggshell membrane extract. Wherein the non-denatured type II collagen has the effects of controlling inflammation, inhibiting collagenase from abnormal metabolism and stimulating type II collagen synthesis in joints, and can supplement essential elements for bone health. The eggshell membrane extract (or eggshell membrane extract) is derived from eggshell membrane, and the eggshell membrane is located between the albumin and calcified shell of egg, and is milky white. It is a double-layered network structure formed by fibrin (such as type I collagen), contains chondroitin sulfate, dermatan sulfate, hyaluronic acid and glycosaminoglycans (GAGs), and eggshell membrane can reduce the expression of proinflammatory cytokines (such as interleukin-1 beta/IL-1 beta), so it can relieve joint pain, repair osteoarticular injury and improve the mobility of arthritis patients.
The protective component comprises at least one of hyaluronic acid, sodium hyaluronate and calcium hyaluronate (the sodium hyaluronate and the calcium hyaluronate are converted into hyaluronic acid HA after being orally taken); hyaluronic Acid (HA) HAs a significant regulatory effect on inflammatory mediators including cytokines, proteases and inhibitors thereof, and prostaglandins. For example, it can inhibit prostaglandin E2 production induced by interleukin-1 in human arthritic cells, which affects adhesion, proliferation, migration and phagocytosis of leukocytes. Hyaluronic Acid (HA) can remove it by interacting with free radicals, and thus HA HAs an effect of protecting chondrocytes from free radical damage. Numerous studies have demonstrated that HA HAs a biological effect on a large number of cells in vivo. HA. hylan a and hylan B (a cross-linked HA gel) also inhibit the production of oxygen free radicals (ODFR) by polymorphonuclear leukocytes induced by stimulatory factors, by the viscoelastic nature of HA solutions, forming a barrier around the cell, preventing contact of stimulatory factors with the cell, thereby inhibiting ODFR production. When degenerative disease occurs in articular cartilage, if exogenous HA viscoelastic solution is supplemented, the development of degenerative disease can be inhibited.
The calcium agent comprises calcium lactate, calcium carbonate and glucoseAt least one of calcium salts. The main effects of calcium agents in arthritis are: (1) calcium supplement can promote the synthesis of articular cartilage matrix. Intracellular Ca when articular cartilage is stimulated by external pressure load 2+ The concentration is obviously increased, and Ca is further activated 2+ The CaM (calmodulin) pathway, which induces an increase in the synthesis of the cartilage matrix. If this signal transduction pathway is abnormal, it may cause abnormalities in the differentiation and formation of chondrocytes, the adhesion of chondrocytes, the repair of articular cartilage, and the responsiveness to stress-load stimulation, leading to the development and progression of arthritis. (2) Conventional calcium supplement can control risk factors (obesity) of arthritis. Epidemiological investigations have shown that there is a significant correlation between how much calcium is ingested and obesity in the population. Insufficient calcium intake in the body promotes fat synthesis, inhibits its decomposition, and ultimately leads to an increase in body fat. Calcium supplementation can regulate this process, reducing the risk of obesity and thus reducing the incidence of osteoarthritis from a risk factor perspective.
Turmeric is used as an anti-inflammatory analgesic ingredient, wherein curcumin has an antioxidant effect by inhibiting oxidative enzymes and scavenging free radicals, thereby preventing the occurrence and development of osteoarthritis. Curcumin can inhibit the consumption of cartilage matrix by matrix metalloproteinase, and increase the production of type II collagen. Curcumin can inhibit the activity of cytosolic phospholipase A2, cyclooxygenase 2, and lipoxygenase 5, thereby achieving anti-inflammatory response. Curcumin can inhibit mitochondrial swelling and apoptosis caused by interleukin 1 beta, and can achieve anti-apoptosis effect. Curcumin or its derivatives have effects of improving osteoarthritis patients, knee joint function, joint pain, etc., but high concentration curcumin has toxic effect on in vitro cultured cells and tissues.
Natto can be used as an ingredient for assisting calcium absorption. Research shows that arthritis and osteoporosis belong to the same aging diseases, the arthritis and the osteoporosis often exist at the same time, and some symptoms of the arthritis can be caused by the osteoporosis. The calcium ions have obvious effects on relieving osteoporosis of arthritis patients, ensuring bone reconstruction of the arthritis patients, reducing the incidence rate of the arthritis and the like, the natto powder is used for preventing the osteoporosis, and the mechanism of auxiliary calcium supplement is as follows: the bone substance is composed of vitamin K 2 And high-quality protein to form bone protein, and then to form bone together with calcium. The natto powder contains soybean isoflavone and vitamin K 2 Soy isoflavones can prevent the dissolution of calcium in bone, and vitamin K 2 Calcium can be fixed in the bone. That is, soybean isoflavones and vitamin K 2 The combination of (A) and (B) can cooperate with each other to play a role of strengthening bones.
According to some embodiments of the invention, the composition comprises the following components in mass ratio: bone strengthening components: a protective component: calcium agent: turmeric: natto = (10-50): (0.1-5): (30-150): (20 to 100): (5-50). For example, the composition comprises the following components: non-denatured type II collagen, sodium hyaluronate, calcium lactate, turmeric and natto powder. The composition comprises the following components in percentage by mass: non-denatured type ii collagen, sodium hyaluronate, calcium lactate, turmeric and natto powder =20:1:90:60:20.
according to some embodiments of the present invention, the eggshell membrane extract is prepared by: treating the eggshell membrane by physical, chemical or enzymatic methods to form the eggshell membrane into a soluble polypeptide mixture; wherein, the physical method comprises pressurization and heating; the chemical processes include acid-base treatment, reduction, and oxidation.
According to some embodiments of the invention, the composition further comprises one or more pharmaceutically acceptable excipients.
According to some embodiments of the invention, the pharmaceutically acceptable excipient comprises a filler, a lubricant, a binder; wherein the filler comprises at least one of microcrystalline cellulose, isomaltulose, calcium hydrogen phosphate, calcium carbonate; the lubricant comprises at least one of magnesium stearate, stearic acid, zinc stearate, calcium stearate, talcum powder and superfine silica powder; the adhesive comprises at least one of methylcellulose, hydroxypropyl methylcellulose, sodium hydroxymethyl cellulose and ethyl cellulose.
According to some embodiments of the invention, the mass ratio of the bone-fixing component to the pharmaceutically acceptable excipient in the composition is (10-50): (150 to 220).
According to some embodiments of the invention, the mass ratio of the filler, lubricant and binder is (150-210): (2-6): (0.5-1.5). For example, the filler is microcrystalline cellulose and isomaltulose, the lubricant is magnesium stearate, and the binder is hydroxypropyl methylcellulose. Wherein, the ratio of microcrystalline cellulose: isomaltulose: magnesium stearate: the mass ratio of the hydroxypropyl methylcellulose is 50.
In a second aspect, the present invention provides a process for preparing a composition as described above, said process comprising: mixing the bone-strengthening component, the protective component, the calcium agent, the turmeric and the natto, and granulating to obtain the composition.
According to some embodiments of the invention, the composition further comprises a filler, a lubricant and a binder, and the preparation method comprises: mixing the calcium agent, the turmeric, the natto, the filler and the adhesive, and performing wet granulation and drying to obtain powder A; mixing the bone fixing component, the protective component, the lubricant and the filler with the powder A to obtain the composition;
wherein the filler comprises at least one of microcrystalline cellulose, isomaltulose, calcium hydrogen phosphate, and calcium carbonate; the lubricant comprises at least one of magnesium stearate, stearic acid, zinc stearate, calcium stearate, talcum powder and superfine silica powder; the adhesive comprises at least one of methylcellulose, hydroxypropyl methylcellulose, sodium hydroxymethyl cellulose and ethyl cellulose.
In a third aspect, the present invention provides the use of a composition as described above for the manufacture of a medicament for the treatment of joint pain or arthritis.
According to some embodiments of the invention, the pharmaceutical dosage form comprises tablets, capsules and powders.
The present invention is further illustrated by the following specific examples, which are specific embodiments of the present invention and are not to be construed as limiting the embodiments of the present invention.
The raw materials used in the following examples and comparative examples are all commercially available products.
Example 1
The preparation method comprises the following steps:
(1) Preparing the components in the amounts shown in Table 1; wherein, taking hydroxypropyl methyl cellulose, preparing into 1% (w/w) solution with 70% ethanol as adhesive solution;
(2) Taking the prescribed amount of turmeric, calcium lactate, natto powder, microcrystalline cellulose and 3/4 of the prescribed amount of isomaltulose for premixing in a wet granulating machine, setting the rotating speed of a stirring paddle to be 10r/s, and mixing for 5min to prepare premixed powder. Adding the adhesive prepared in the step (1) into the premixed powder, setting the rotating speed of a stirring paddle to be 10r/s and the rotating speed of a cutter to be 4r/s, and preparing wet particles;
(3) Drying the wet granules prepared in the step (2) by using a fluidized bed at the drying temperature of 45 ℃ for 20min to prepare dry granules; granulating the dry granules by using a 18-mesh screen to prepare granulated powder;
(4) Mixing the non-denatured type II collagen, sodium hyaluronate, magnesium stearate and 1/4 of isomaltulose in the prescribed weight parts with the granulated powder by a two-dimensional mixer for 10min at the mixing speed of 10r/m to prepare total mixed powder;
(5) Tabletting the total mixed powder prepared in the step (4) by using a tabletting machine to prepare the composition tablet; or filling the obtained total mixed powder with a capsule filling machine to obtain the composition capsule; or the prepared total mixed powder is packaged by total mixed particles of the powder to prepare the composition powder. The prepared tablets and capsules are all bottled.
Examples 2 to 10
The preparation method is the same as that of example 1, the specific formula composition is shown in tables 1, 2 and 3, and the parts in tables 1-3 are parts by weight.
Table 1 formulation composition table in examples 1 to 4
Tables of formulations of examples 5 to 8 were prepared by replacing the non-denatured type II collagen of examples 1 to 4 with eggshell membrane extract in addition to examples 1 to 4. The specific formulation composition is shown in table 2.
Table 2 examples 5 to 8 formulation composition table
Example 9 is based on example 1, calcium lactate was replaced by calcium carbonate and sodium hyaluronate by hyaluronic acid. Example 10 is prepared by replacing calcium lactate with calcium gluconate and sodium hyaluronate with calcium hyaluronate, based on example 2. The specific formulation is shown in table 3.
Table 3 examples 9-10 recipe composition table
Comparative examples 1 to 6
Comparative example 1 is a placebo control, comparative example 2 is no non-denatured type ii collagen added based on example 4, comparative example 3 is no sodium hyaluronate added based on example 4, comparative example 4 is no turmeric added based on example 4, comparative example 5 is no calcium lactate added based on example 4, and comparative example 6 is no natto powder added based on example 4. The specific formulation composition is shown in Table 4, and the "parts" in Table 4 are parts by weight.
TABLE 4 COMPARATIVE EXAMPLES 1-6 FORMULATION TABLE
And (3) testing:
1. animal experiments
1.1 animal experimental design:
180 KM male mice (purchased from the center of test animals in Hebei province) with similar body weight and age were selected, the body weight was about 20g, and no significant difference was observed between individuals, and the 180 mice were randomly assigned to 18 groups of 10 mice each, each of which was designated as a normal group, a model group, a placebo group (comparative example 1), a non-denatured type II collagen control group (comparative example 2), a sodium hyaluronate-free control group (comparative example 3), a turmeric-free control group (comparative example 4), a calcium lactate-free control group (comparative example 5), a natto-free powder control group (comparative example 6), and example 1-10 groups.
1.2 methods of causing inflammation: the Mao Jianqu of the right hind plantar aspect of each mouse in the model group, all control groups and example group was sterilized with alcohol, and then inserted along the superficial layer of the skin with a 4-gauge fine needle using a bcg vaccine syringe, followed by slowly injecting 0.1ml of complete freund's adjuvant, and when the drug solution was injected into the skin, orange peel-like vesicles immediately appeared on the skin surface, and Mao Za was very prominent on the skin due to ischemia at the injection site. If the small bubble disappears very quickly, the liquid medicine is really injected into the skin, if the small bubble disappears very quickly, the liquid medicine can be injected into the skin, and the liquid medicine needs to be injected into the skin again. After molding, the above control examples 1 to 6 and examples 1 to 10 were dissolved to prepare a solution having a concentration of 0.1g/ml, and the mice of the control examples 1 to 6 and examples 1 to 10 were gavaged with 1ml at 8 am daily for 24 consecutive days. In addition, placebo was dissolved to prepare a solution having a concentration of 0.1g/ml, and the placebo group mice were also subjected to rat gavage for 1ml at 8 am daily for 24 days. The dosing schedule for these 18 groups is recorded in table 5.
TABLE 5 dosing schedules for normal, model, control and experimental groups
Selection of serum biochemical indices
In the treatment of osteoarthritis, the protection and repair of articular cartilage are the primary targets of treatment, interleukin-1 beta is an important proinflammatory factor and plays an important role in promoting the occurrence and development of osteoarthritis, the research on treatment based on interleukin-1 beta is gradually advanced, and due to the importance of interleukin-1 beta in the development of osteoarthritis, the control of interleukin-1 beta level is generally considered to be the target for improving the development of osteoarthritis.
A large number of experiments and clinics find that the expression frequency of nitric oxide in the bone joint fluid, chondrocytes and synovium is obviously related to the index of the bone arthritis, so that the nitric oxide is considered to be an important mediating factor for the generation and development of the bone arthritis, can cause the damage of the articular chondrocytes, is a powerful inflammatory medium in the bone arthritis cartilage damage, and after a Nitric Oxide Synthase (NOS) inhibitor is applied, the content of NO in the joint fluid is reduced, the phenomenon of the cartilage cell apoptosis is reduced, and the NO is shown to be one of important mediums for causing the cartilage cell apoptosis in the experimental bone arthritis.
Free radicals are atoms, molecules or genes with unpaired electrons, are in a stable structural state, and have active chemical properties. Free radicals involved in life phenomena, called biological free radicals, are oxygen radicals, which are often responsible for the generation of other free radicals, more than 95% of total free radicals in the human body, mainly active oxygen, superoxide anion free radicals, and the like, which are oxidants initiating lipid peroxidation in organisms. Under normal conditions, the production and elimination of free radicals in vivo are in relative equilibrium due to the presence of free radical scavengers such as superoxide dismutase and glutathione peroxidase and catalase. And the content of oxygen free radicals in the body of a patient with Osteoarthritis (OA) is increased, excessive oxygen free radicals in joints inhibit chondrocyte proliferation to cause chondrocyte death, and the synthesis of cartilage matrix proteoglycan and collagen is inhibited to accelerate the degradation of cartilage matrix, so that the cartilage cells are damaged. Reactive oxygen radicals can attack chondrocyte DNA directly. So that the collagen is subjected to oxidative damage, a plurality of hydroxyl radicals cause the change of basic groups and glycosyl groups in DNA and DNA protein cross-linking in nuclear protein, and the cartilage collagen is made rigid. Malondialdehyde (MDA) is a product of lipid peroxidation, superoxide dismutase (SOD) is a scavenger of superoxide anion, and the content of MDA and SOD can indirectly reflect the level of oxygen free radicals in vivo.
1.3 serum biochemical index determination method:
interleukin-1 β: the determination is carried out according to the radioimmunity contract box method II-1B radioimmunity of the general hospital science and technology development center of the liberty military.
Nitric oxide: the determination is carried out according to the method of establishing a nitric oxide (nitric acid reductase method) kit of bioengineering research institute in Nanjing.
Malondialdehyde: the determination is carried out according to the method of the exempting MDA (single reagent) kit of the scientific and technological development center of the general hospital of the liberation force.
Superoxide dismutase: the determination was carried out according to the method of superoxide dismutase radioimmunoassay kit (PR method) of Shanghai research Ltd.
The detection sample acquisition method comprises the following steps: 24 days after treatment, mouse sera were collected by the mouse eyeball removal method and tested as described above. Table 6 shows the values of serum biochemical indices of the mice in the normal group, model group, control group and experimental group.
TABLE 6 Biochemical index values of sera of mice in the normal, model, control and experimental groups
Remarking: * Representing a significant difference from the model group (P < 0.05), & representing a very significant difference from the model group (P < 0.01), # not significantly different from the normal group (P > 0.05).
And (4) conclusion: the indexes of the inflammation-causing factors and the antioxidant factors of the embodiments 1 to 3 and the embodiments 5 to 10 are obviously different from the comparison of a model group, and the treatment effect of the embodiments is proved to be obvious. The optimal examples 4 and 8 of the composition have significant difference with the model group ratio and have no significant difference with the normal group ratio. Therefore, the components in the composition have a synergistic effect, and the combined application of the components can reduce the inflammation of mice, so that the joint pain of patients is reduced, the repair of the joint cartilage is promoted, the joint function is improved, the joint cartilage is prevented from being further degenerated and changed, and no adverse reaction such as gastrointestinal discomfort, diarrhea and the like is observed, thereby proving that the composition provided by the invention is safe and effective.
2. Experiment of human body effect
2.1 Experimental methods
Selecting 15 outpatient gonitis patients, randomly dividing the outpatient gonitis patients into 3 groups, taking tablets prepared in placebo groups and examples 4 and 8 respectively for 5 patients in each group, randomly performing double-blind intervention on the 3 groups, evaluating the clinical symptom improvement condition before and after intervention and the change condition of the articular cartilage structure and function by using the average WOMAC arthritis index score and the VAS pain score scale, and performing statistical analysis.
The basic method of the Visual Analogue Scale (VAS) VAS is to use a moving ruler, a slide 10cm long without scale on the front, a slidable scale between the "0" and "10" ends, the "0" end representing no pain, the "10" end representing the most severe pain that is difficult to tolerate, and a scale of "0 to 10" on the back. During clinical use, the patient is carried to the one side back that will have the scale, and the patient slides calibration object to corresponding position according to painful intensity, and the back of painful dipperstick has specific scale, can directly read out painful degree index according to the position of calibration object. The patient marks the corresponding position on the line or ruler for the degree of pain or functional limitation of the patient. The average value of mild pain is 2.57 +/-1.04, the average value of moderate pain is 5.18 +/-1.41, and the average value of moderate pain is 8.41 +/-1.35.
WOMAC knee joint score scale: this scoring scale contains 3 major aspects of pain, stiffness and joint function, and has a total of 24 items that can objectively assess the basic symptoms and signs of arthritis. Higher WOMAC index identifies more severe arthritis and the severity of arthritis is assessed according to the total score by the following criteria: the mild degree is less than or equal to 80, the moderate degree is 80-120, and the severe degree is more than or equal to 120.
Test results are shown in tables 7 and 8.
Comparison of VAS scores before and after subject intervention is shown in table 7.
TABLE 7 comparison of VAS scores before and after subject intervention
| Group of | Before tasting | Eating for 15 days | Taking 30 days | Tasting for 60 days |
| Placebo group | 5.13±0.38 | 5.10±0.44* | 5.24±0.43* | 5.19±0.44* |
| Example 4 | 5.38±0.19* | 4.75±0.15 & | 4.02±0.07 & | 3.51±0.08 & |
| Example 8 | 5.29±0.22* | 4.68±0.27 & | 4.05±0.45 & | 3.45±0.23 & |
Remarking: * Represents no significant difference (P is more than 0.05) compared with the placebo group before the test feeding, represents significant difference (P is less than 0.05) compared with the patients in the group before the test feeding, and represents very significant difference (P is less than 0.01) compared with the patients in the group before the test feeding.
A comparison of WOMAC knee scores before and after subject intervention is shown in table 8.
TABLE 8 comparison of WOMAC Knee Joint scores before and after subject intervention
| Group of | Before tasting | Eating for 15 days | Taking 30 days | Tasting for 60 days |
| Placebo group | 63.37±0.63 | 62.66±0.44* | 62.46±1.60* | 62.87±1.12* |
| Example 4 | 64.09±5.78* | 57.49±7.57 & | 51.93±8.29 & | 46.29±10.65 & |
| Example 8 | 63.49±4.59* | 55.17±7.95 & | 46.26±6.43 & | 37.33±4.41 & |
Remarking: * Represents no significant difference (P is more than 0.05) compared with the placebo group before the test feeding, represents significant difference (P is less than 0.05) compared with the patients in the group before the test feeding, and represents very significant difference (P is less than 0.01) compared with the patients in the group before the test feeding.
And (4) evaluating the results: as can be seen from tables 7 and 8, the pain results were not reduced after taking placebo for 15 days, 30 days, and 60 days, but the pain of the patients was significantly reduced after taking the product of examples 4 and 8, as compared to the pain before taking the product. Therefore, the components in the composition have synergistic effect, and the combined application of the components in the composition can relieve joint pain of a patient in a short time, relieve inflammation of the patient, promote repair of joint cartilage, improve joint function, prevent further degenerative change of the joint cartilage, and is safe and effective without adverse reactions such as gastrointestinal discomfort, diarrhea and the like. The compositions provided in the present invention prove safe and effective.
Example 11
Wang Mou, female, age 52, has degenerative arthritis with osteoporosis, joint hidden pain, obvious pain when walking stairs, and friction sound often associated with bone joints. After taking the capsule prepared from the composition in example 4 for 30 days, joint pain and walking pain are reduced, and frictional sound is reduced, so that the user can go up and down stairs normally and walk without joint frictional sound after keeping taking the capsule prepared from the composition in example 4 for 3 months.
While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (10)
1. A composition for relieving joint pain or treating arthritis, wherein the composition comprises the following components:
bone-strengthening component, protecting component, calcium agent, turmeric and natto;
wherein the bone fixing component comprises at least one of non-denatured type II collagen and eggshell membrane extract;
the protective component comprises at least one of hyaluronic acid, sodium hyaluronate and calcium hyaluronate;
the calcium agent comprises at least one of calcium lactate, calcium carbonate and calcium gluconate.
2. The composition according to claim 1, wherein the composition comprises the following components in percentage by mass:
bone strengthening components: a protective component: calcium agent: turmeric: natto = (10-50): (0.1-5): (30-150): (20 to 100): (5-50).
3. The composition of claim 1, wherein the eggshell membrane extract is prepared by:
treating the eggshell membrane by physical, chemical or enzymatic methods to form the eggshell membrane into a soluble polypeptide mixture; wherein, the physical method comprises pressurization and heating; the chemical processes include acid-base treatment, reduction, and oxidation.
4. The composition of claim 1, further comprising one or more pharmaceutically acceptable excipients.
5. The composition of claim 4, wherein the pharmaceutically acceptable excipients comprise fillers, lubricants, binders;
wherein the filler comprises at least one of microcrystalline cellulose, isomaltulose, calcium hydrogen phosphate, calcium carbonate;
the lubricant comprises at least one of magnesium stearate, stearic acid, zinc stearate, calcium stearate, talcum powder and superfine silica powder;
the adhesive comprises at least one of methylcellulose, hydroxypropyl methylcellulose, sodium hydroxymethyl cellulose and ethyl cellulose.
6. The composition according to claim 4, wherein the mass ratio of the bone-fixing component to the pharmaceutically acceptable excipient in the composition is (10-50): (150 to 220).
7. A method of preparing the composition of claim 1, wherein the method comprises:
mixing the bone-strengthening component, the protective component, the calcium agent, the turmeric and the natto, and granulating to obtain the composition.
8. The method of claim 7, wherein the composition further comprises a filler, a lubricant, and a binder, and the method comprises:
mixing the calcium agent, the turmeric, the natto, the filler and the adhesive, and performing wet granulation and drying to obtain powder A;
mixing the bone fixing component, the protective component, the lubricant and the filler with the powder A to obtain the composition;
wherein the filler comprises at least one of microcrystalline cellulose, isomaltulose, calcium hydrogen phosphate, and calcium carbonate; the lubricant comprises at least one of magnesium stearate, stearic acid, zinc stearate, calcium stearate, talcum powder and superfine silica powder; the adhesive comprises at least one of methylcellulose, hydroxypropyl methylcellulose, sodium hydroxymethyl cellulose and ethyl cellulose.
9. Use of a composition according to any one of claims 1 to 6 in the manufacture of a medicament for the treatment of joint pain or arthritis.
10. The use according to claim 9, wherein the pharmaceutical dosage form comprises tablets, capsules and powders.
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