WO2021179319A1 - Composition containing hydrolyzed chondroitin sulfate for preventing and treating osteoarthropathy - Google Patents

Abstract

A composition containing hydrolyzed chondroitin sulfate for preventing and treating osteoarthropathy and a preparation method therefor. Effective components of the composition have high bioavailability, low dosages, and can be used to restore bone function.

Description

Composition containing hydrolyzed chondroitin sulfate for preventing and treating osteoarthropathy Technical field

The invention belongs to the field of health food, and particularly relates to a hydrolyzed chondroitin sulfate composition.

Background technique

Chondroitin sulfate is a mucopolysaccharide substance extracted from cartilage tissues such as animal larynx and trachea. Its basic units are D-glucuronic acid and N-acetyl-D-galactosamine sulfate. Chondroitin sulfate is a macromolecular substance with diverse biological activities. With its unique pharmacological activity, it has a wide range of applications in the fields of medicine and health products. It can not only treat bone and joint diseases, lower blood lipids, but also can be used as a nutritional health product to improve Body immunity. At present, the molecular weight of chondroitin sulfate on the market is generally 10kDa-50kDa. This type of chondroitin sulfate has a relatively large molecular weight and is difficult to penetrate biological cell membranes. Therefore, it cannot perform its various pharmacological functions well in the body. There are literature reports on human biological utilization. The degree is about 10% to 15%, which seriously affects the curative effect. After entering the human gastrointestinal tract, digestion through the digestive juice of the gastrointestinal tract will cause obvious irritation to the upper digestive tract. Stomach pain, stomach acid, bloating, and even Symptoms such as nausea and vomiting. A large number of studies have shown that low molecular weight chondroitin sulfate has the advantages of low viscosity and good solubility, has higher bioavailability, and better promotes cartilage repair and other effects. Therefore, the preparation of hydrolyzed chondroitin sulfate by enzymatic hydrolysis of chondroitin sulfate is used to prepare health foods that increase bone density, improve osteoporosis, and relieve arthritis. The irritation is less.

Summary of the invention

The problem to be solved by the present invention is to provide a hydrolyzed chondroitin sulfate composition for increasing bone density and alleviating arthritis. The daily human dosage of the hydrolyzed chondroitin sulfate and glucosamine composition is lower than that of currently known commercially available sulfuric acid. The daily human dosage of chondroitin and glucosamine composition. For example, the daily human dosage of chondroitin sulfate and glucosamine in Movefree is 1700mg/day; the daily human dosage of chondroitin sulfate and glucosamine in By-Health is 1160mg/day. sky. By reducing the dosage to improve the compliance of taking, but does not reduce the effect of increasing bone density and relieving arthritis.

In order to achieve the above-mentioned purpose of the invention, a hydrolyzed chondroitin sulfate composition of the present invention adopts the following technical solutions:

The composition containing hydrolyzed chondroitin sulfate of the present invention is characterized in that it contains a daily dosage of 50 mg to 800 mg of hydrolyzed chondroitin sulfate.

The composition containing hydrolyzed chondroitin sulfate of the present invention is characterized in that the composition may contain glucosamine.

The composition containing hydrolyzed chondroitin sulfate according to the present invention is characterized in that the glucosamine can be one or a mixture of glucosamine hydrochloride and glucosamine sulfate.

The composition containing hydrolyzed chondroitin sulfate of the present invention is characterized in that the hydrolyzed chondroitin sulfate is a mixture of hydrolyzed chondroitin sulfate with different molecular weights.

The hydrolyzed chondroitin sulfate composition of the present invention is a mixture obtained by enzymatic hydrolysis, purification, concentration, and spray drying of chondroitin sulfate, and its molecular weight is 379-10000 Da.

The composition containing hydrolyzed chondroitin sulfate of the present invention further includes pharmaceutically acceptable excipients, wherein the excipients are selected from fillers, disintegrants, adhesives, correctives, and lubricants. And film coating agent

The hydrolyzed chondroitin sulfate composition of the present invention and the preparation method thereof are characterized in that the filler in the preparation includes, but is not limited to, microcrystalline cellulose, starch, dextrin, mannitol, lactose, etc.; disintegration Agents include, but are not limited to, crospovidone, croscarmellose sodium, sodium carboxymethyl starch, hydroxypropyl starch, pre-crossed starch, low-substituted hydroxypropyl cellulose, sodium bicarbonate, citrate Acid, tartaric acid, etc.; binders include but are not limited to sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, etc.; lubricants include But not limited to magnesium stearate, micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycol, stearic acid, etc.; the composition of the film coating agent includes but is not limited to hydroxypropyl methyl cellulose, polyethylene glycol, color Dian etc.

The hydrolyzed chondroitin sulfate composition and the preparation method thereof of the present invention are characterized in that the preparation includes, but is not limited to, tablets, granules, capsules, and pills.

The composition of the present invention can be used to prepare medicines for reducing arthritis and alleviating pain.

Compared with the prior art, the hydrolyzed chondroitin sulfate prepared by enzymatically hydrolyzing chondroitin sulfate of the present invention can be used to prepare health care products that increase bone density, improve osteoporosis, and relieve arthritis. Less irritating. The daily human dosage of the components of the hydrolyzed chondroitin sulfate and glucosamine contained in the composition of the present invention is lower than the currently known human daily dosage of commercially available chondroitin sulfate and glucosamine. By reducing the dosage to improve the compliance of taking, but does not reduce the effect of increasing bone density and relieving arthritis. The test of the difference in support force of mice is used to evaluate the pain degree of mouse arthritis and the daily dosage of human body. It shows that the daily dosage of hydrolyzed chondroitin sulfate between 50～800mg can significantly relieve and treat the pain of osteoarthritis. The effect of adding glucosamine to the composition can increase the effect of relieving and curing osteoarthritis pain.

Description of the drawings

Figure 1 A diagram of the effect of the composition on the body weight of mice.

Figure 2 A diagram of the influence of the composition on the supporting force of mice.

Detailed ways

The content of the present invention will be further described in detail below in conjunction with specific embodiments, but the protection scope of the present invention is not limited to these embodiments.

Example 1: Hydrolyzed chondroitin sulfate capsules

prescription:

Preparation:

(1) Pass the hydrolyzed chondroitin sulfate and microcrystalline cellulose through an 80-mesh sieve for use;

(2) After mixing the hydrolyzed chondroitin sulfate and microcrystalline cellulose uniformly, add the prescribed amount of crospovidone, micronized silica gel and magnesium stearate in sequence, and mix for 15 minutes;

(3) Pour the mixture into the capsule shell through a capsule filling machine to get it.

Example 2: Hydrolyzed Chondroitin Sulfate Tablets

prescription:

Preparation:

(1) Pass the hydrolyzed chondroitin sulfate and microcrystalline cellulose through an 80-mesh sieve for use;

(2) After mixing the hydrolyzed chondroitin sulfate and microcrystalline cellulose uniformly, add the prescribed amount of croscarmellose sodium, micronized silica gel and magnesium stearate in sequence, and mix for 15 minutes;

(3) Press the mixture through a rotary tablet press to control the tablet hardness to 6-10kg;

(4) Use purified water to prepare a coating solution with a solid content of 10%;

(5) Coat the tablets with a high-efficiency coating machine, set the inlet air temperature to 55°C, the atomization pressure to 0.2MPa, and control the tablet bed temperature to 40-45°C, and it will be obtained after the coating is completed.

Example 3: Hydrolyzed Chondroitin Sulfate Tablets

prescription:

Preparation:

(1) Pass the hydrolyzed chondroitin sulfate and lactose through an 80-mesh sieve for use;

(2) After mixing the hydrolyzed chondroitin sulfate and lactose evenly, add the prescribed amount of hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, micronized silica gel and magnesium stearate in sequence, and mix for 15 minutes;

(3) Press the mixture through a rotary tablet press to control the tablet hardness to 6-10kg;

(4) Use purified water to prepare a coating solution with a solid content of 10%;

(5) Coat the tablets with a high-efficiency coating machine, set the inlet air temperature to 55°C, the atomization pressure to 0.2MPa, and control the tablet bed temperature to 40-45°C, and it will be obtained after the coating is completed.

Example 4: Hydrolyzed Chondroitin Sulfate Tablets

Components:

Preparation:

(1) Pass the hydrolyzed chondroitin sulfate, starch, and dextrin through an 80-mesh sieve for use;

(2) After mixing the hydrolyzed chondroitin sulfate, starch and dextrin evenly, sequentially add the prescribed amount of hydroxypropyl cellulose, sodium carboxymethyl starch, micronized silica gel and magnesium stearate, and mix for 15 minutes;

(3) Press the mixture through a rotary tablet press to control the tablet hardness to 6-10kg;

(4) Use purified water to prepare a coating solution with a solid content of 10%;

(5) Coat the tablets with a high-efficiency coating machine, set the inlet air temperature to 55°C, the atomization pressure to 0.2MPa, and control the tablet bed temperature to 40-45°C, and it will be obtained after the coating is completed.

Example 5: Hydrolyzed Chondroitin Sulfate Capsules

Example 6: Hydrolyzed Chondroitin Sulfate and Glucosamine Sulfate Tablets

prescription

Preparation:

(1) Pass the hydrolyzed chondroitin sulfate, glucosamine sulfate, microcrystalline cellulose and lactose through an 80-mesh sieve respectively for use;

(2) After mixing the hydrolyzed chondroitin sulfate, glucosamine sulfate, microcrystalline cellulose and lactose uniformly, sequentially add the prescribed amount of croscarmellose sodium, micronized silica gel and magnesium stearate, and mix for 15 minutes;

(3) Press the mixture through a rotary tablet press to control the tablet hardness to 6-10kg;

(4) Use purified water to prepare a coating solution with a solid content of 10%;

(5) Coat the tablets with a high-efficiency coating machine, set the inlet air temperature to 55°C, the atomization pressure to 0.2MPa, and control the tablet bed temperature to 40-45°C, and it will be obtained after the coating is completed.

Example 7: Mouse medial meniscus instability (DMM) model test of the composition prepared by the present invention

1. Material

1.1. Test sample: The composition is prepared according to Examples 1-6 of the present invention. Example 1, Example 2, Example 3, Example 4, Example 5 and Example 6 The recommended daily dosage for humans is 2 tablets (Capsules)/day, 1 tablet (capsule) each morning and evening.

1.2. Preparation of the test substance: the test sample is mixed into the feed to give the sample, example 1, example 2, example 3, example 4, example 5 and example 6, samples taken by mice every day Requires 150mg/day.

1.3. The route of administration of the test substance: the samples of each example were administered to each group of animals by gavage.

2. Model establishment

The mouse was anesthetized with chloral hydrate, the knee joint hair of the right hind limb was shaved, and after iodine alcohol disinfection, an opening about 1 cm long was cut longitudinally along the inner side of the mouse bone to expose the knee joint. Use microsurgical scissors to open the joint cavity and cut the tibial ligament of the medial meniscus with the medial meniscus rivet on the tibial plateau. The 6-0 absorbable suture is used to suture the joint capsule, the 6-0 suture is used to suture the skin of the joint, and a small amount of penicillin is applied to the sutured skin to prevent infection. The blank group (9 mice) did the same operation, but did not cut the tibial ligament of the medial meniscus. On the second day after the operation, the DMM mice were randomly divided into 7 groups (1, model control group; 2, Example 1 group; 3, Example 2 group; 4, Example 3 group; 5, Example 4 group; 6. Example 5 group; 7. Example 6 group) 13 animals in each group.

3. Experimental results

On the second day after the operation, the mice were given intragastric administration. The blank group and the model group were given the same volume of normal saline. It is administered once a day for 12 consecutive weeks, and the animal weight is weighed once a week, and the dosage is adjusted according to the body weight.

Table 1 The effect of the composition prepared by the present invention on the body weight of mice (n=13,

)

Experimental conclusion: As shown in Figure 1, from the 0th day of the experiment, the weight of each group of mice showed a slight upward trend, and there was no significant difference between the groups at each time point (P>0.05).

After the mice were gavaged for 12 weeks, the YLS-11A channel type mouse foot support force measuring instrument was used to detect the difference in the support force of the two hind legs of each group of mice when they were standing, so as to evaluate the degree of osteoarthritis pain in the mice. . The mice were driven into a single channel for a 60-degree climbing experiment. When the mouse began to climb and stand, record the difference in support between the left and right hind legs of the mouse. The greater the difference in supporting force, the more severe the degree of osteoarthritis.

Table 2 The influence of the composition prepared by the present invention on the supporting force of the hind foot of mice (n=13,

)

The pain degree of osteoarthritis in mice was evaluated by detecting the difference in support force of mice. The results are shown in Figure 2. The difference in foot support force of the model group is the largest, indicating that the pain degree of osteoarthritis in the model group is the most severe . There was a very significant difference between the sham operation group and the sham operation group (P<0.01), indicating that the model was successfully established. Compared with the model group, Example 1, Example 2, Example 5 and Example 6 can significantly reduce the difference in foot support force (P<0.01), and Example 3 and Example 4 can also reduce the difference in foot support force ( P＜0.05), the daily dose of mice is calculated according to the formula: human dose=mouse dose*human body weight/equivalent dose ratio, and the calculation process is as follows:

Remarks: 1. The equivalent dose ratio between mice and humans is 9.1; 2. The dose of hydrolyzed chondroitin sulfate in mice = the dose of mouse composition * prescription amount of hydrolyzed chondroitin sulfate/total tablet weight.

It shows that the daily dosage of hydrolyzed chondroitin sulfate between 50 and 800 mg has a relatively obvious effect of relieving and curing osteoarthritis pain, and the addition of glucosamine in the composition can increase the effect of relieving and curing osteoarthritis pain.

In short, the above description of the specific embodiments of the present invention does not limit the present invention. Those skilled in the art can make various changes or modifications according to the present invention, as long as they do not deviate from the spirit of the present invention, they shall fall within the scope of the appended claims of the present invention. .

Claims (9)

1. A composition containing hydrolyzed chondroitin sulfate is characterized in that it contains a daily dosage of 50 mg to 800 mg of hydrolyzed chondroitin sulfate.
2. The composition containing hydrolyzed chondroitin sulfate according to claim 1, wherein the composition may contain glucosamine.
3. The composition containing hydrolyzed chondroitin sulfate according to claim 2, wherein the glucosamine can be one or a mixture of glucosamine hydrochloride and glucosamine sulfate.
4. The composition containing hydrolyzed chondroitin sulfate according to claim 1, wherein the hydrolyzed chondroitin sulfate is a mixture of hydrolyzed chondroitin sulfate with different molecular weights.
5. The composition containing hydrolyzed chondroitin sulfate according to claim 4, wherein the average molecular weight of the hydrolyzed chondroitin sulfate is 379-10000 Da.
6. The composition containing hydrolyzed chondroitin sulfate according to claim 1, wherein the composition further comprises pharmaceutically acceptable excipients, wherein the excipients are selected from the group consisting of fillers, disintegrants, adhesives, and correctives. Flavoring agent, lubricant and film coating agent.
7. The composition containing hydrolyzed chondroitin sulfate according to claim 6, wherein the fillers include but are not limited to microcrystalline cellulose, starch, dextrin, mannitol, lactose; disintegrants include but are not limited to Crospovidone, croscarmellose sodium, carboxymethyl starch sodium, hydroxypropyl starch, pre-crossed starch, low-substituted hydroxypropyl cellulose, sodium bicarbonate, citric acid, tartaric acid; viscous Mixtures include but are not limited to sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone; lubricants include but are not limited to magnesium stearate , Micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycol, stearic acid; the composition of the film coating agent includes but not limited to hydroxypropyl methyl cellulose, polyethylene glycol, lake.
8. The composition containing hydrolyzed chondroitin sulfate according to claim 1, wherein the dosage form of the composition includes, but is not limited to, tablets, granules, capsules, and pills.
9. The composition according to any one of claims 1-8, wherein the composition can be used to prepare medicines for reducing joint inflammation and relieving pain.

Images