CN108815505A - Improve the composition that middle-aged and the old's bone density and osteoarticular function avoid waist-leg from knotting - Google Patents

Abstract

The invention relates to a composition for improving bone density and bone and joint functions of middle-aged and elderly people and avoiding waist and leg cramps. The composition consists of 500 parts by weight of Pueraria root extract, 400-500 parts by weight of glucosamine hydrochloride, 300-500 parts by weight of calcium carbonate, 50-150 parts by weight of chondroitin sulfate, 10-40 parts by weight of casein phosphopeptide, and optionally made in a physiologically acceptable carrier. Tests have proved that the composition of the invention has excellent effects of improving bone density of middle-aged and elderly people, enhancing bone and joint functions, and preventing waist and leg cramps. The present invention also relates to the preparation method of the above composition and their use in the preparation of products for improving the bone density and bone and joint functions of middle-aged and elderly people and avoiding waist and leg cramps.

Description

Composition for improving bone density and bone and joint function of middle-aged and elderly people to avoid waist and leg cramps

technical field

The invention belongs to the technical field of medical and health care products, and relates to a traditional Chinese medicine composition for increasing bone density, improving bone and joint functions, avoiding or reducing waist and leg cramps for middle-aged and elderly people, and also relates to a preparation method of the composition, and their Medical, pharmaceutical use, and more particularly to a composition made of casein and kudzu root.

Background technique

People will lose different degrees of bone density after middle-aged and old people, and the related physiological manifestations are decreased bone and joint function, and frequent waist and leg cramps.

The full name of bone mineral density (BMD) is bone mineral density, which is an important indicator of bone strength, expressed in grams per cubic centimeter, and is an absolute value. When using bone density values clinically, because the absolute values of different bone density detectors are different, the T value is usually used to judge whether the bone density is normal. The T value is a relative value, and the normal reference value is between -1 and +1. When the T value is lower than -2.5, it is abnormal. Bone mineral density is an important marker of bone quality, reflecting the degree of osteoporosis and an important basis for predicting the risk of fracture. Due to the increasing improvement of measurement methods and the development of advanced software, the method can be used in different parts, and the measurement accuracy has been significantly improved. In addition to diagnosing osteoporosis, it can also be used for clinical drug effect observation and epidemiological investigation, and has significant advantages in predicting osteoporotic fractures. The bone mineral density value of healthy Han people in northern China, determine the peak bone density age, size and normal value of each age group. DXA was used to measure the bone mineral density of lumbar spine L2--L4 and hip. The results show that the age of peak bone mineral density in men is 20--24 years old, and the density value of L2--L4 is 1.228 (g/cm3); the peak age of lumbar spine in women is 30--34 years old, and the value is 1.197 (g/cm3) . The peak bone density of the hip is between 25 and 29 years old. At the International Osteoporosis Foundation (IFO) World Congress on Osteoporosis in 2004, Johnell and others from the WHO Metabolic Bone Disease Research Center at the University of Sheffield, UK, conducted a meta-analysis of 12 clinical studies and concluded that whether male or female, bone Density (BMD) is a very important fracture risk factor. The study included 39,000 people in 12 population studies, observed for a total of about 170,000 person-years. The Poisson model was used to analyze the influence of BMD on the risk of fracture in each study population, and the weighting coefficient was used to combine the results of each study. The results showed that BMD was a good predictor of fractures, especially hip fractures, in both men and women. In the 65-year-old age group, the risk of hip fracture increased by 2.94 times (2.02-4.27) for men and 2.88 times (2.31-3.59) for women for every 1 standard deviation (SD) decrease in BMD. However, this effect was age-dependent, with a significantly higher risk gradient at age 50 than at age 80. The risk gradients of various types of fractures and osteoporotic fractures were lower than those of hip fractures, and the predictive value of BMD increased with age. In the 65-year-old age group, for every 1 SD decrease in BMD, the risk of osteoporotic fracture increased by 1.41 times (1.33-1.51) in men and 1.38 times (1.28-1.41) in women. For hip fractures, the predictive value of BMD decreased, but not significantly, with a longer interval between fracture and measurement of BMD. The lower the BMD value, the greater the effect of predicting osteoporotic fractures (and various types of fractures). The hazard ratio when the T value is reduced by 4 SD is 2.10 (1.63--2.71) The hazard ratio when the T value is reduced by 1 SD It is 1.73 (1.59--1.89). For hip fractures, BMD was similarly predictive. According to Johnell et al., since the selected clinical research is international, the conclusions drawn from the analysis results have good application value. The results of this analysis indicated that BMD can be used to screen susceptible cases, however, in the process of application, the influence of age on the predictive value of BMD fracture should be considered. The method of improving bone density can be based on the different causes and mechanism of bone density deficiency, and different raw materials can be selected when designing the formula of health food. Commonly used raw materials are as follows: 1. Calcium: If calcium absorption is normal, just give 1.00-1.50 grams per day. Among various calcium preparations, calcium carbonate is widely used. For the elderly over 65 years old, 0.75 grams to 2.5 grams per day. For those who use estrogen with many side effects and the possibility of inducing endometrial cancer, giving large doses of calcium can have the same effect as using estrogen. Patients with kidney stones should not take a large amount of calcium. 2. Vitamin D and its active products: In the past, it was believed that senile osteoporosis patients were often accompanied by vitamin D deficiency, so it was advocated to give more vitamin D. In fact, except for the combination of osteomalacia (generally speaking, only children are prone to osteomalacia , such as rickets), intestinal calcium absorption disorders and reduced production of vitamin D metabolites, generally do not need to supplement a large amount of vitamin D, and those who do have the above three conditions can be given vitamin D at the same time. 3. Calcitonin: Calcitonin can reduce bone absorption, reduce calcium in blood circulation, and increase calcium content in bone. Since calcitonin can reduce blood calcium, calcium should be supplemented when using calcitonin. Play a role in the treatment of osteoporosis. 4. Phosphates: The treatment of osteoporosis with phosphates has been developed in recent years. Phosphates can promote bone formation and inhibit the destruction of bone cells, and can be used for a long time. 5. n-3 polyunsaturated fatty acid (α-linolenic acid): n-3 fatty acid affects human bone metabolism, regulates osteoblasts and osteoclasts through different mechanisms, and strengthening n-3 fatty acid is beneficial Improve bone density.

Bone joints are connected by capsules of connective tissue between adjacent bones. Bone-to-bone indirect connections are called bone joints. There is a cavity between the opposite bone surfaces, and the cavity contains a small amount of synovial fluid. It has a large range of motion, and each joint has an articular surface, a joint capsule, and a joint cavity. Certain joints also have auxiliary structures such as ligaments, articular discs, and menisci. The reason why the human body can move freely is because of the structure of bone joints. Most of the bone joints not only provide the needs of human activities, but also protect the bones from wear and tear through cartilage. Regarding the maintenance of bones and joints, hydroxyproline is a vehicle for transporting calcium to bone cells in plasma, and collagen in bone cells is the binder of hydroxyapatite, which together with hydroxyapatite constitute the main body of bones . Therefore, as long as enough collagen is taken in, the calcium intake of the normal body can be guaranteed, and collagen can be made into a calcium-supplementing health food. Osteoarthrosis is based on acute or chronic damage to articular cartilage or degeneration of articular cartilage. According to clinical findings, most osteoarthritis occurs in the elderly. Changes in joint structure relationship. It is a frequently-occurring disease in orthopedic outpatient clinics, a common disease. Osteoarthrosis is a chronic joint disease characterized by local articular cartilage degeneration, bone loss, joint edge spur formation, joint deformity and subchondral bone density, also known as osteoarthritis, degenerative osteoarthritis, hyperplasia arthritis, senile arthritis. It occurs more frequently in people over 50 years old, and women are more common than men. The disease affects the quality of life of middle-aged and elderly patients to varying degrees. Almost all cases have varying degrees of pain, slowly progressing with the course of the disease. The main manifestation is that the pain is obvious when the joint starts to move, and the pain is relieved after a little movement. However, when the weight is loaded and the bone joint is moved too much, the pain will aggravate again, which is the characteristic of osteoarthritis. Sometimes the pain can be radiated, such as hip joint pain can radiate to the inner thigh, near the knee joint. Joint stiffness can be seen in the early stage. For example, when the knee joint is in a certain position for a long time, the conscious movement is unfavorable, and it is difficult to start. Then, the joint instability gradually occurs, the range of joint flexion and extension activities is reduced, and the walking ability is reduced, especially when going up and down stairs, squatting, running, The decline in jumping and other abilities is more obvious. Some patients with advanced osteoarthritis may also have some lower limb deformities, the most common of which is genu varus, which is commonly known as "bandy legs". In the treatment of osteoarthritis, the main considerations are as follows: 1. Functional exercise: Reasonable exercise can restore muscle contractility, joint flexibility and prevent and treat osteoporosis. Unreasonable exercise will increase joint load and cause cartilage damage. further damage, which aggravates the clinical symptoms. It is often seen that some patients have aggravated symptoms after blindly walking long distances, dancing disco, or even running, climbing and other uncomfortable exercises. We advocate that exercise should be performed without weight-bearing on the joints. It is recommended that the healthy limb bear weight on the ground, the affected limb should be flexed and extended, or the joint should be flexed and extended while sitting. Try not to do squats and other activities that will increase the load on the joints. For hip joints and knee joints, you can practice sit-ups, straight leg raises, etc. on the bed, the more times the better. Swimming is a very suitable exercise for patients with knee osteoarthritis. It does not put much burden on the knee joint and can fully activate the muscles. But breaststroke requires a strong twisting of the knee joint. Sometimes it will cause bad results, so it is recommended to use freestyle and backstroke. 2. Improve awareness of prevention: patients should understand the harmfulness of the disease and the importance of early treatment, improve patients' awareness of risk factors, eliminate and avoid pathogenic factors, and help control the disease and restore function. Confidence. 3. Protect the joints: limit the weight-bearing activities of the joints, avoid standing for a long time or walking for a long distance, and use a cane to reduce the load on the affected joints; those who are overweight should lose weight; pay attention to keeping the affected joints warm and avoiding wind and cold; in severe cases, short-term Bed rest and full braking. 4. Local physical therapy: In the acute stage of joint fever and swelling, local cold compresses should be applied first, and hot compresses can be applied after the fever and swelling are reduced. In the chronic phase, infrared rays, ultrashort waves, acupuncture, wax therapy, massage, etc. can also be applied.

Lumbar and leg cramps, the scientific name is muscle spasm, which is a spontaneous mandatory contraction of muscles. Leg cramps mainly occur in the muscles of the calf and toes. The pain is unbearable during the attack, especially in the middle of the night when the cramps often wake people up. It is difficult to relieve the pain for a long time and affects sleep. The main causes of waist and leg cramps are: ①Cold stimulation. Such as exercising in a cold environment in winter, insufficient preparation activities; swimming in summer with low water temperature can easily cause leg cramps. Sleeping at night without a good quilt, the calf muscles will be stimulated by the cold, and they will wake up painfully due to spasms. ② continuous muscle contraction too fast. During strenuous exercise, the whole body is in a tense state, the leg muscles contract too quickly, and the relaxation time is too short, the local metabolite lactic acid increases, and it is difficult to coordinate muscle contraction and relaxation, thus causing calf muscle spasms. ③ Excessive sweating. If you exercise for a long time, exercise a lot, sweat a lot, and do not replenish salt in time, the body will lose a lot of fluids and electrolytes, and metabolic waste will accumulate. The blood circulation in the muscles is not good, and cramps are prone to occur. ④ Excessive fatigue. When traveling long distances, climbing mountains, or climbing high, the calf muscles are most prone to fatigue. Because every time you climb a height, one foot supports the whole body weight. The muscles in this leg need to lift the foot six times the body weight. When it gets tired to a certain extent, it will cramp. ⑤ Calcium deficiency. Calcium ions play an important role in muscle contraction. When the concentration of calcium ions in the blood is too low, the muscles are easily excited and spasm. Teenagers grow and develop rapidly and are prone to calcium deficiency, so leg cramps often occur. ⑥ Poor sleeping posture. Such as lying on the back for a long time, pressing the quilt on the feet, or lying on the stomach for a long time, making the feet rest on the bed, forcing certain muscles of the calf to be in a state of absolute relaxation for a long time, causing muscle "passive contracture". ⑦ frequent frequent occurrence may be related to vascular disease.

Those skilled in the art still look forward to a new method to improve the bone density of middle-aged and elderly people, enhance the function of bones and joints, and avoid waist and leg cramps. Those skilled in the art still look forward to new medicines or health care products in order to be used to improve the bone density of middle-aged and elderly people, enhance bone and joint function, and avoid waist and leg cramps.

Contents of the invention

The purpose of the present invention is to provide a new method for improving the bone density of middle-aged and elderly people, enhancing bone and joint function, and avoiding waist and leg cramps. Another purpose of the present invention is to provide a new medicine or health care product for improving the The bone density of the elderly, enhance bone and joint function, and avoid waist and leg cramps. It has been unexpectedly found that the composition obtained from the prescription of the present invention has excellent functions of improving bone density of middle-aged and elderly people, enhancing bone and joint functions, and avoiding waist and leg cramps. , and exhibit one or more excellent technical effects. The present invention has been accomplished based on this finding.

To this end, the first aspect of the present invention provides a composition for improving bone density and bone and joint function in middle-aged and elderly people and avoiding waist and leg cramps, which includes: kudzu root extract, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate, casein phosphopeptide, and optionally a physiologically acceptable carrier.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps comprises: 500 parts by weight of kudzu root extract, 400-500 parts by weight of glucosamine hydrochloride, 300-300 parts by weight of calcium carbonate 500 parts by weight, 50-150 parts by weight of chondroitin sulfate, 10-40 parts by weight of casein phosphopeptide, and optional physiologically acceptable carrier.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps comprises: 500 parts by weight of kudzu root extract, 400-500 parts by weight of glucosamine hydrochloride, 300-300 parts by weight of calcium carbonate 500 parts by weight, 50-150 parts by weight of chondroitin sulfate, 10-40 parts by weight of casein phosphopeptide, and optional physiologically acceptable carrier.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps comprises: 500 parts by weight of kudzu root extract, 420-470 parts by weight of glucosamine hydrochloride, 350-350 parts by weight of calcium carbonate 450 parts by weight, 75-125 parts by weight of chondroitin sulfate, 20-30 parts by weight of casein phosphopeptide, and optional physiologically acceptable carrier.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps comprises: 500 parts by weight of Pueraria root extract, 440 parts by weight of glucosamine hydrochloride, 400 parts by weight of calcium carbonate, 100 parts by weight of chondroitin sulfate, 25 parts by weight of casein phosphopeptide, and optional physiologically acceptable carrier.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people to avoid waist and leg cramps is in the form of tablets or granules.

According to the first aspect of the present invention, it is in the form of a tablet, and the physiologically acceptable carrier includes xylitol and microcrystalline cellulose for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps. ,Magnesium stearate.

According to the first aspect of the present invention, the composition for improving bone mineral density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps is in the form of tablets, and the amount of xylitol is 500 parts by weight of Pueraria root extract. 500-1000 parts by weight, such as 600-900 parts by weight, such as 700-800 parts by weight, such as 760 parts by weight.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps is in the form of tablets, and the amount of microcrystalline cellulose is based on 500 parts by weight of kudzu root extract. It is 200-300 parts by weight, such as 220-280 parts by weight, such as 240-260 parts by weight, such as 250 parts by weight.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps is in the form of tablets, and the amount of magnesium stearate is calculated per 500 parts by weight of kudzu root extract. It is 20-30 parts by weight, such as 22-28 parts by weight, such as 24-26 parts by weight, such as 25 parts by weight.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps is prepared according to the method comprising the following steps:

(1) make Pueraria root extract and glucosamine hydrochloride mix uniformly, make calcium carbonate and chondroitin sulfate mix uniformly in addition;

(2) Dissolve the casein phosphopeptide with 5-8 times the amount of water, then add xylitol 2-3 times the weight of the casein phosphopeptide, mix evenly, and let the mixture be ventilated at 60-70°C for 2.5 ~3 hours, mix well;

(3) Mix the various mixtures obtained in the above two steps, add microcrystalline cellulose and the remaining amount of xylitol to it, mix well, add water as a lubricant, prepare wet granules, and dry the wet granules;

(4) Mix the dried granules obtained in the previous step with magnesium stearate uniformly to obtain the composition, which is directly packaged in the form of granules, or further compressed into tablets to obtain granules or tablet formulations.

According to the first aspect of the present invention, the composition for improving bone density and bone and joint function of middle-aged and elderly people to avoid waist and leg cramps is in the form of tablet preparation. In one embodiment it is in the form of a chewable tablet.

It has been found surprisingly that the composition prepared in this way (compared to Casein phosphopeptides are not treated with xylitol in this way) can avoid the discoloration of the drug after long-term storage. The specific experiment is: with reference to Example 1 to Example 5 respectively, the difference is that in step (2), the casein phosphopeptide is uniformly mixed with the corresponding amount of xylitol, and this mixture is directly used in the subsequent steps to obtain 5 batches of available samples. Respectively referred to as the tablets of Supplementary Example 1 to Supplementary Example 5; the tablets of Example 1 to Example 5 and the tablets of Supplementary Example 1 to Supplementary Example 5 were placed at a temperature of 40° C. for 6 months, and the 0 month and In June, the tablet was dissolved in water and filtered to make a solution containing 20 μg/ml of casein phosphopeptide (after June, the color of the solutions in Examples 1 to 5 was obviously lighter than that in Supplementary Examples 1 to 5), and the absorbance was measured at 360nm For each sample, the following formula calculates its absorbance increase percentage: absorbance increase percentage=[6 month absorbance-0 month absorbance]÷0 month absorbance×100%; As a result, the absorbance increase percentage of embodiment 1～embodiment 5 tablet 3.3% to 7.4%, and the percent increase in absorbance of Supplementary Example 1 to Supplementary Example 5 tablets was 36.7% to 47.2%, and the latter was higher than the former, indicating that the latter tablets were more likely to change color and deepen in color.

Further, the second aspect of the present invention provides a method for preparing a composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps. The composition includes: kudzu root extract, glucosamine hydrochloride, carbonic acid Calcium, chondroitin sulfate, casein phosphopeptide, and xylitol, microcrystalline cellulose, magnesium stearate, the method comprises the following steps:

(1) make Pueraria root extract and glucosamine hydrochloride mix uniformly, make calcium carbonate and chondroitin sulfate mix uniformly in addition;

(2) Dissolve the casein phosphopeptide with 5-8 times the amount of water, then add xylitol 2-3 times the weight of the casein phosphopeptide, mix evenly, and let the mixture be ventilated at 60-70°C for 2.5 ~3 hours, mix well;

(3) Mix the various mixtures obtained in the above two steps, add microcrystalline cellulose and the remaining amount of xylitol to it, mix well, add water as a lubricant, prepare wet granules, and dry the wet granules;

(4) Mix the dried granules obtained in the previous step with magnesium stearate uniformly to obtain the composition, which is directly packaged in the form of granules, or further compressed into tablets to obtain granules or tablet formulations.

According to the method of the second aspect of the present invention, wherein the composition for improving bone density and bone and joint function of middle-aged and elderly people to avoid waist and leg cramps includes: 500 parts by weight of Pueraria root extract, 400-500 parts by weight of glucosamine hydrochloride, carbonic acid 300-500 parts by weight of calcium, 50-150 parts by weight of chondroitin sulfate, 10-40 parts by weight of casein phosphopeptide, and optional physiologically acceptable carriers.

According to the method of the second aspect of the present invention, wherein the composition for improving bone density and bone and joint function of middle-aged and elderly people to avoid waist and leg cramps includes: 500 parts by weight of Pueraria root extract, 400-500 parts by weight of glucosamine hydrochloride, carbonic acid 300-500 parts by weight of calcium, 50-150 parts by weight of chondroitin sulfate, 10-40 parts by weight of casein phosphopeptide, and optional physiologically acceptable carriers.

According to the method of the second aspect of the present invention, wherein the composition for improving bone density and bone and joint function of middle-aged and elderly people to avoid waist and leg cramps includes: 500 parts by weight of Pueraria root extract, 420-470 parts by weight of glucosamine hydrochloride, carbonic acid 350-450 parts by weight of calcium, 75-125 parts by weight of chondroitin sulfate, 20-30 parts by weight of casein phosphopeptide, and optional physiologically acceptable carriers.

According to the method of the second aspect of the present invention, wherein the composition for improving bone density and bone and joint function of middle-aged and elderly people to avoid waist and leg cramps includes: 500 parts by weight of Pueraria root extract, 440 parts by weight of glucosamine hydrochloride, 400 parts by weight of calcium carbonate parts by weight, 100 parts by weight of chondroitin sulfate, 25 parts by weight of casein phosphopeptide, and optional physiologically acceptable carriers.

According to the method of the second aspect of the present invention, wherein in the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps, the amount of xylitol is 500 parts per 500 parts by weight of kudzu root extract. -1000 parts by weight, eg 600-900 parts by weight, eg 700-800 parts by weight, eg 760 parts by weight.

According to the method of the second aspect of the present invention, wherein in the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps, the amount of microcrystalline cellulose is 500 parts by weight of Pueraria root extract. 200-300 parts by weight, such as 220-280 parts by weight, such as 240-260 parts by weight, such as 250 parts by weight.

According to the method of the second aspect of the present invention, wherein in the composition for improving bone density and bone and joint function of middle-aged and elderly people and avoiding waist and leg cramps, the amount of magnesium stearate is 20-30 parts by weight, such as 22-28 parts by weight, such as 24-26 parts by weight, such as 25 parts by weight.

Further, the third aspect of the present invention provides a composition comprising kudzu root extract, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate, casein phosphopeptide, and an optional physiologically acceptable carrier. Use in products for bone density and bone and joint function of the elderly to avoid waist and leg cramps.

According to the use of the third aspect of the present invention, the composition includes: 500 parts by weight of kudzu root extract, 400-500 parts by weight of glucosamine hydrochloride, 300-500 parts by weight of calcium carbonate, 50-150 parts by weight of chondroitin sulfate, casein 10-40 parts by weight of phosphopeptide, and optional physiologically acceptable carrier.

According to the use of the third aspect of the present invention, the composition includes: 500 parts by weight of kudzu root extract, 400-500 parts by weight of glucosamine hydrochloride, 300-500 parts by weight of calcium carbonate, 50-150 parts by weight of chondroitin sulfate, casein 10-40 parts by weight of phosphopeptide, and optional physiologically acceptable carrier.

According to the use of the third aspect of the present invention, the composition includes: 500 parts by weight of kudzu root extract, 420-470 parts by weight of glucosamine hydrochloride, 350-450 parts by weight of calcium carbonate, 75-125 parts by weight of chondroitin sulfate, casein 20-30 parts by weight of phosphopeptide, and optional physiologically acceptable carrier.

According to the use of the third aspect of the present invention, the composition includes: 500 parts by weight of kudzu root extract, 440 parts by weight of glucosamine hydrochloride, 400 parts by weight of calcium carbonate, 100 parts by weight of chondroitin sulfate, 25 parts by weight of casein phosphopeptide, and optionally a physiologically acceptable carrier.

According to the use of the third aspect of the present invention, the composition is in the form of tablets or granules.

According to the use of the third aspect of the present invention, the composition is in the form of a tablet, and the physiologically acceptable carrier includes xylitol, microcrystalline cellulose, and magnesium stearate.

According to the use of the third aspect of the present invention, the amount of xylitol in the composition is 500 to 1000 parts by weight, such as 600 to 900 parts by weight, such as 700 to 800 parts by weight, such as 760 parts by weight.

According to the use of the third aspect of the present invention, the amount of microcrystalline cellulose in the composition is 200-300 parts by weight, such as 220-280 parts by weight, such as 240-260 parts by weight, based on 500 parts by weight of the kudzu root extract. For example 250 parts by weight.

According to the use of the third aspect of the present invention, the amount of magnesium stearate in the composition is 20-30 parts by weight, such as 22-28 parts by weight, such as 24-26 parts by weight, per 500 parts by weight of Pueraria root extract, For example 25 parts by weight.

According to the purposes of the third aspect of the present invention, the composition is prepared according to the method comprising the following steps:

(1) make Pueraria root extract and glucosamine hydrochloride mix uniformly, make calcium carbonate and chondroitin sulfate mix uniformly in addition;

(2) Dissolve the casein phosphopeptide with 5-8 times the amount of water, then add xylitol 2-3 times the weight of the casein phosphopeptide, mix evenly, and let the mixture be ventilated at 60-70°C for 2.5 ~3 hours, mix well;

(3) Mix the various mixtures obtained in the above two steps, add microcrystalline cellulose and the remaining amount of xylitol to it, mix well, add water as a lubricant, prepare wet granules, and dry the wet granules;

(4) Mix the dried granules obtained in the previous step with magnesium stearate uniformly to obtain the composition, which is directly packaged in the form of granules, or further compressed into tablets to obtain granules or tablet formulations.

In the method steps described in the present invention, although the specific steps described in it are different from the steps described in the examples of the specific embodiment section below in some details or language descriptions, those skilled in the art according to the present invention The detailed disclosure of the full text can fully summarize the above-mentioned method steps.

Any embodiment of any aspect of the present invention may be combined with other embodiments as long as they do not contradict each other. In addition, in any embodiment of any aspect of the present invention, any technical feature can be applied to the technical feature in other embodiments, as long as there is no contradiction between them.

The present invention will be further described below.

All the documents cited in the present invention are incorporated herein by reference in their entirety, and if the meaning expressed in these documents is inconsistent with the present invention, the expression of the present invention shall prevail. In addition, various terms and phrases used in the present invention have common meanings known to those skilled in the art. Even so, the present invention still hopes to make a more detailed description and explanation of these terms and phrases here. The terms and phrases mentioned are as follows: If there is any inconsistency with the known meaning, the meaning expressed in the present invention shall prevail.

Pueraria lobata (Willd.) Ohwi is the dried root of Pueraria lobata (Willd.) Ohwi or Puerariathomsonii Benth. Excavated in autumn and winter, Pueraria lobata is mostly cut into thick slices or small pieces while it is fresh; dry; Pueraria vine is commonly known as "Fenge", and the outer skin is mostly removed, smoked with sulfur, dried slightly, cut into sections or cut into two lengthwise. half, dry. Pueraria lobata: longitudinally cut rectangular thick slices or small cubes, 5-35cm long and 0.5-1cm thick. The outer skin is light brown, has longitudinal wrinkles, and is rough. The cut surface is yellowish white, and the texture is not obvious. Tough and strong fibrous. Odorless, slightly sweet taste. Pueraria: Cylindrical, fusiform or semi-cylindrical, 12-15cm long, 4-8cm in diameter; some are thick slices cut longitudinally or obliquely, with different sizes. The surface is yellowish white or light brown, and the unskinned ones are grayish brown. Light brown concentric rings formed by fibers can be seen on the transverse section, and several longitudinal lines formed by fibers can be seen on the longitudinal section. Heavy, hard, powdery. Radix Puerariae is sweet, pungent, and cool in taste. Return spleen, stomach warp. It has the effects of relieving muscle and reducing fever, promoting body fluid, clearing rash, promoting yang and stopping diarrhea. For exogenous fever and headache, stiff neck and back pain, thirst, thirst, impervious measles, febrile dysentery, diarrhea; high blood pressure and stiff neck. Puerarin contains isoflavone components puerarin, puerarin xyloside, daidzein, daidzein, β-sitosterol, arachidic acid, and a large amount of starch (19-20% in fresh pueraria). The dry root of Gan kudzu vine contains 37% starch. The root of Pueraria trilobata contains 15-20% starch. Puerarin, daidzein, daidzein, β-sitosterol, 4′, 6″-diacetylpuerarin and stigmasterol have been isolated from the roots of plants of the same genus in India. It has been reported that Pueraria mirifica contains daidzein ( daidzein), daidzin (daidzin), puerarin (puerarin), 4'-methoxypuerarin (4'-methoxypuerarin), daidzein-4',7-diglucoside (daidzein-4',7- diglucoside), daidzein-7-(6-O-malonyl)-glucoside [daidzein-7-(6-O-malonyl)-lucoside], genistein (genistein), formononetin ( for-mononetin), daidzein-8-C-apiosyl(1→6)-glucoside [daidzein-8-C-apiosyl(1→6)-glucoside], genistein-8-C-celery Glycosyl (1→6)-glucoside [genistein-8-C-apiosyl(1→6)-glucoside], puerarin xyloside (puerarinxyloside, PG-2), 3'-hydroxypuerarin (3'- hydroxypuerarin, PG-1), 3'-methoxypuerarin (3'-methoxypuerarin, PG-3), 4'-O-glucosyl puerarin (4'-O-glucosyl puerarin, PG-6), kudzu root Phenol (puerarol), puerarin (pueroside) A, B, formononetin-7-glucoside (formononetin-7-glucoside), lupenone (lupenone), β-sitosterol (β-sitosterol), di Docosanoic acid, Tetracosanoic acid, Glucerol-1-monotetracosanoate, Allantoin, β-sitosterol-β- D-glucoside (β-sitosteryl-β-D-glucoside), 6,7-dimethoxycoumarin (6,7-dimethoxycoumarin), 5-methylhydantoin (5-methylhydantoin) and Sophora japonica Sophoradiol, cantoniensistriol, soyasapogenol A, B, kudzusapogenol C, A and kudzusapogenol B methylester are aglycones Triterpene saponins. Pueraria also contains daidzein, daidzin, puerarin and beta-sitosterol. The root of kudzu root contains daidzein, puerarin, 4'-methoxypuerarin, daidzein and trace daidzein-4,7'-diglucoside. The pharmacological effects of kudzu root mainly include the following aspects: ①The effect on the circulatory system, the flavonoids proposed in kudzu root can increase the blood flow of brain and coronary vessels. After injection of kudzu flavonoids into the internal carotid artery of anesthetized dogs, the cerebral blood flow increases, and the vascular resistance decreases accordingly, and the effect lasts for 2 to 20 minutes. If intravenous injection, the cerebral blood flow increases slightly, and the contraction of epinephrine and norepinephrine cannot be relieved. Cerebrovascular effect, but for patients with hypertension and arteriosclerosis, it can improve cerebral circulation, and its effect is mild. Pueraria flavonoids and pueraria wine extract injected into the coronary arteries and veins of dogs can increase coronary blood flow and reduce vascular resistance. Giving rats intraperitoneal and subcutaneous injections of pueraria root wine extract and intraperitoneal injection of its water decoction and the crystals proposed in pueraria lobata have protective effects on the cardiac ischemic reaction caused by pituitary hormone, and oral administration of pueraria root water decoction has a protective effect on hypertension. Dogs have no obvious antihypertensive effect. Pueraria decoction (produced in Japan) is reported to have two components of stimulating and inhibiting the heart. ② Antispasmodic effect, Chinese pueraria (variety not specified) and Japanese Pueraria commercially available both contain astragalus flavonoids, which have papaverine-like antispasmodic effects on the isolated intestines of mice and guinea pigs. The spasmodic effect is strong, which may be related to the large amount of flavonoids contained in it. This antispasmodic component can resist the effects of histamine and acetylcholine; other isoflavone derivatives isolated from Japanese kudzu root have no obvious effect on expanding acetylcholine. In addition, substances that have a contractile effect on the intestinal tube of the elbow have been isolated, and MTF-101, which is produced in Pueraria lobata from Japan, has a muscarinic effect. ③ Hypoglycemic effect, Pueraria lobata (species not specified) decoction is given to rabbits orally, blood sugar rises in the first 2 hours, then drops, and drops to the lowest in the 3rd and 4th hours, not only has no resistance to adrenaline hyperglycemia in rabbits, but makes The increase, but can promote blood sugar return to normal early. Pueraria root water extract can also make the blood sugar of rabbits rise initially and then fall, and the effect of raising blood sugar in hungry rabbits is more significant, while the ether extract has no obvious effect on glucose metabolism. ④ antipyretic and estrogen-like effects, the Pueraria root infusion produced in Japan has obvious antipyretic effect on rabbits with artificial fever, which lasts for 4 to 5 hours. Pueraria lobata can increase the weight of the uterus of immature mice, and has estrogen-like effects. The active ingredient for this effect is daidzein. The kudzu root extract used in the present invention can also be called the total flavonoids of kudzu root, which complies with the provisions of the national drug standard YBZ013422006-2009Z. This kudzu root extract is obtained by extracting kudzu root through water extraction, and currently there are finished products on the market.

Glucosamine, Glucosamine, also known as D-glucosamine, usually uses its hydrochloride, and its sulfate is also used. Glucosamine is a compound in which one hydroxyl group of glucose is replaced by an amino group. Molecular formula C6H13O5N, commonly known as amino sugar, referred to as amino sugar. Also known as glucosamine, widely present in nature, 2-amino-2-deoxy-D-glucose is usually in the form of N-acetyl derivatives (such as chitin) or in the form of N-sulfate and N-acetyl-3-O-lactic acid The ether (muramic acid) form is present in microorganisms, polysaccharides of animal origin and conjugated polysaccharides. It is mainly suitable for degenerative arthritis of the knee joint, hyperosteogeny, and meniscus injury. Glucosamine, which is a substance synthesized in the human body, is an important nutrient for the formation of chondrocytes and a natural tissue component of healthy articular cartilage. As we grow older, the lack of glucosamine in the body becomes more and more serious, and the articular cartilage continues to degenerate and wear away. A large number of medical studies in the United States, Europe and Japan have shown that glucosamine can help repair and maintain cartilage, and can stimulate the growth of chondrocytes. The main functions of glucosamine are: Relieve pain, stiffness and swelling caused by arthritis; Osteoporosis depletes cartilage, eventually leading to fragmentation and peeling, less cartilage cushioning in joints, prone to stiffness and inflammation. Glucosamine helps repair damaged cartilage, stimulates the formation of new cartilage, improves inflammation, and relieves joint pain, stiffness and swelling. Strengthen cartilage structure and prevent joint function failure: As the body ages, joint tissue will be severely worn. Glucosamine can protect and strengthen cartilage structure and prevent joint function failure due to joint aging. Lubricate joints and maintain joint function: Glucosamine can produce proteoglycans to lubricate joints, prevent bone and joint friction and pain, and make joints move freely. The therapeutic functions of glucosamine mainly include: 1. Knee degenerative arthritis. Glucosamine treats knee arthritis mainly by repairing articular cartilage and promoting joint synovial fluid, so that there will no longer be hard friction between the articular surfaces, and no pain will occur. Symptoms such as swelling, bone friction sound, etc., and through the repair of articular cartilage, the joint space will return to normal, and the joint function will be completely restored. 2. Bone hyperplasia, exogenous intake of glucosamine, restores the balance of glucosamine content in the joint, stimulates chondrocytes to synthesize proteoglycan and collagen fibers, generates cartilage matrix, repairs damaged cartilage, and improves the self-repair ability of articular cartilage. Glucosamine repairs articular cartilage and promotes joint synovial fluid, which has a fundamental therapeutic effect on osteoproliferative arthritis (osteoarthritis). 3. For meniscus damage, glucosamine can repair the damaged meniscus, and at the same time repair the damage of articular surface cartilage secondary to meniscus damage, and fundamentally repair joint damage. Glucosamine can remove harmful factors, inhibit and eliminate the inflammatory reaction of joint synovium. 4. For patella softening, exogenous supplementation of glucosamine can repair the articular cartilage between the patella and femur. 5. Nerve root type of cervical spondylosis. 6. Cervical spondylosis myeloid type. 7. Vertebral artery type of cervical spondylosis. 8. Sympathetic type of cervical spondylosis, glucosamine can eliminate soft tissue edema by inhibiting the inflammatory response of intervertebral joint soft tissue, and repair damaged cartilage ring, so that intervertebral disc herniation is not easy to burst, and promote the normal secretion of joint synovial fluid, so that the neck can move Be more flexible. 9. For synovitis, glucosamine can relieve pain, swelling and other symptoms by removing harmful substances in the joint cavity and repairing articular cartilage and diseased synovium. 10. For hand osteoarthritis, supplementing with glucosamine can repair worn articular cartilage and relieve joint pain caused by worn articular cartilage. 11. For foot osteoarthritis, after taking glucosamine, glucosamine can repair the wear of articular cartilage. If taken for a long time, it has a good protective effect on the ankle joints of athletes who often exercise vigorously. For periarthritis of shoulder, glucosamine repairs soft tissues such as tendons, ligaments, synovium, and bursa by promoting the synthesis of proteoglycan and collagen fibers, promotes the production of synovial fluid in joints and bursae, relieves adhesion of soft tissue in joints, and improves the function of shoulder joints. recover. For lumbar disc herniation, glucosamine supplementation can significantly improve the degeneration of intervertebral articular cartilage and intervertebral disc fibrocartilage ring, and relieve the pain of patients. Rheumatism, arthritis, rheumatoid arthritis will lead to the destruction of articular cartilage, supplementing glucosamine can repair the wear and tear of articular cartilage and reduce the pain of patients. 15. Supplement calcium ions needed by the body, enhance bone growth and health. Glucosamine is a derivative of natural amino monosaccharide, which is an important component necessary for the synthesis of proteoglycan in cartilage matrix. Proteoglycans can make articular cartilage have the function of absorbing impact by inhibiting the stretching force of collagen fibers. In the early stages of joint degenerative disease, aggrecan biosynthesis is increased; in the later stages of the disease, the opposite is true. As a result, the elasticity of the cartilage is continuously weakened and many symptoms of arthritis gradually appear. Amino monosaccharides can stimulate chondrocytes to produce glycoproteins with normal multimer structure, inhibit some enzymes (such as collagenase) that can damage articular cartilage, prevent corticosteroids and some non-steroidal anti-inflammatory drugs from damaging chondrocytes and Reduces the release of endotoxin factors that damage cells. In the development of arthritis, supplementation of exogenous glucosamine may play a beneficial role. In in vitro tests, cartilage-forming polymorphic cells synthesized more aggregated glucan if they were supplemented with glucosamine. In animal models of arthritis, glucosamine also has antioxidant effects, inhibiting the production of superoxide free radicals that damage cells. Through the above pathways, glucosamine exerts a direct anti-inflammatory effect, which can relieve the pain symptoms of osteoarthritis, improve joint function, and prevent the development of osteoarthritis. 90% of glucosamine is absorbed when taken orally, quickly diffuses into the blood through biological barriers, and distributes to tissues and organs, especially has an affinity for articular cartilage, can diffuse into the matrix of articular cartilage, and reach chondrocytes. The plasma concentration reaches the peak value 4 hours after oral administration. From 1 to 8 hours after taking the medicine, the concentration of glucosamine in the liver, kidney, stomach wall, small intestine, brain, bone, muscle and articular cartilage can be measured to increase successively. 24h the composition decreased. t1/2 is 18h. Glucosamine is metabolized by the liver into smaller molecules that are eventually broken down into carbon dioxide, water, and urea. 10% of the oral dose is excreted through urine, 11% is excreted through feces, and most of the rest is excreted through the expiratory tract in the form of carbon dioxide. There are also some studies reporting different results. Barclay believes that after oral administration of glucosamine, it is combined with plasma protein through the first-pass effect, and the bioavailability is 26%, and the unbound glucosamine part is concentrated in the articular cartilage. In vitro tests suggest that when glucosamine produces various effects, its blood concentration needs to be higher than 100mmol·L-1. Biggee et al gave 1500 mg of glucosamine to 18 osteoarthritis patients who had fasted overnight, and took blood samples at a certain time. The drug concentration in the blank blood sample was lower than 0.5mmol·L-1, and the maximum blood drug concentration in the test was 11.5mmol·L-1, which was far lower than the concentration required to obtain in vitro curative effect in other studies. Therefore, researchers such as Biggee questioned the efficacy of glucosamine, because these effects are based on the biological theory of high concentrations in current in vitro studies. Glucosamine is used to treat osteoarthritis in various parts, such as osteoarthritis in knee joint, hip joint, hand joint, etc. Since the listing of glucosamine, a number of clinical studies have been carried out at home and abroad. Symptom improvement: In 1994, Noack et al conducted a multicenter, randomized, placebo-controlled study to evaluate the effectiveness and safety of glucosamine. 252 outpatients with osteoarthritis were randomly divided into groups according to Lequesne's index assessment (radiological grades I to III, Lequesnez index of at least 4 points, and symptoms for at least 6 months). Glucose 500mg (treatment group) or placebo (control group), 3 times a day, medication for 4 weeks. At the beginning of the study, the Lequesne index of each group was (10.6±0.45) points. At the end of the study, the treatment group decreased to (7.45±0.5) points (average reduction of 3.2 points), and the placebo group was (8.4±0.4) points (average reduction of 2.2 points) (P<0.05, S test). The effective rates of the treatment group and the placebo group were 55% (n=120) and 38% (n=121) respectively. The patient tolerance was good, and no significant difference was found between the two groups. This study shows that glucosamine is a safe and effective slow-acting drug for the treatment of osteoarthritis. Structural improvement: In 2001, through a randomized double-blind placebo-controlled clinical trial, Reginster et al. studied the long-term effects of glucosamine on osteoarthritis. 212 patients with knee osteoarthritis were randomized to take 1500mg glucosamine or placebo every day for 3 years. Anteroposterior X-ray photographs were taken before and 1 year and 3 years after treatment, and the average width of the tibial and femoral joint medial space was determined by digital image analysis. The minimum joint cavity width is the narrowest part of the joint cavity, observed with a magnifying glass. Symptom scoring was performed according to WOMAC. The results of the study showed that the average narrowing degree of the progressive joint space confirmed by X-ray film was 0.31mm in the placebo group, but there was no significant change in the glucosamine group (1500mg·d-1), which was only 0.06mm. There are significant differences. Patients who took a placebo had slightly worse symptoms than those treated with glucosamine. Safety and reasons for early withdrawal from the trial did not differ significantly between the treatment and placebo groups. It is therefore believed that long-term treatment with glucosamine may prevent the development of knee OA. The glucosamine used in the present invention is purchased from the market and complies with the standard specified on page 226 of the sixteenth volume of the national standard of chemical medicine of the State Drug Administration.

Calcium carbonate is the most common form of calcium supplementation for humans. Calcium ions are indispensable ions for various physiological activities of the body. It maintains the biological potential on both sides of the cell membrane and maintains normal nerve conduction function. Calcium ions are used to maintain normal muscle contraction and relaxation functions, as well as nerve-to-muscle conduction functions, as well as the mechanism of action of some hormones. Calcium ion is the existing form of calcium element in the compound. A calcium atom loses two electrons and becomes a calcium ion. Calcium (Ca) is one of the important components of the human body and generally exists in the form of calcium ions. Calcium has a large content in the human body, most of which exist in bones and teeth, and a small amount exists in blood and tissues. Due to metabolism, a certain amount of calcium needs to be supplemented from food every day. The recommended daily intake for adults is 1,000 mg, and 1,300 mg for long-term adults. Therefore, teenagers need more calcium than adults because of the need for bone development. Height development is related to genetics, but it is also related to acquired nutrition. Ensuring adequate nutrition, including calcium, is important, which is why people today are taller than their parents on average. Calcium ions are found in various foods, and milk and dairy products are the most abundant. For example, 200 ml of milk (about a cup) contains about 300 mg of calcium ions. So even if you have a bad appetite, two glasses of milk are enough. If you really want to supplement, eat more soy products, spinach and other foods with high calcium content. Natural food with balanced nutrition is the best choice. Calcium ions are indispensable ions for various physiological activities of the body. It maintains the biological potential on both sides of the cell membrane and maintains normal nerve conduction function. Calcium ions are used to maintain normal muscle contraction and relaxation functions, as well as nerve-to-muscle conduction functions, as well as the mechanism of action of some hormones. Its main physiological functions are based on the above basic cell functions, mainly as follows: 1. Calcium ion is a coagulation factor and participates in the blood coagulation process; 2. Participates in the contraction process of muscles (including skeletal muscles and smooth muscles); 3. Participates in nerve Transmitter synthesis and release, hormone synthesis and secretion; 4. It is an important substance for bone formation. The mechanism of several important effects is as follows: transmission of nerve signals, mechanism: promotion of neurotransmitter secretion. When the first cell is excited, an electrical impulse is generated. At this time, extracellular calcium ions flow into the cell, prompting the cell to secrete a neurotransmitter, which binds to the protein on the membrane of the adjacent next-level nerve cell. The molecules bind, prompting this level of nerve cells to generate new electrical impulses. By analogy, the neural signals are passed down step by step, thus forming a complex signal system, and eventually the advanced functions of the brain such as learning and memory appear. When the body lacks calcium, the release of neurotransmitters is blocked, and the excitatory and inhibitory mechanisms of the human body are destroyed. If children are calcium deficient, they will cry at night, night terrors, irritability and insomnia, and seriously lead to brain development disorders, such as unresponsiveness, hyperactivity, learning difficulties, etc., affecting brain maturity and intelligence. To make the heart beat, the mechanism: positively charged calcium ions cause a potential difference between the inside and outside of the cell. Positively charged calcium ions pass through the cell membrane and enter the cardiomyocytes. Because the calcium concentration inside and outside the cell is quite different, a large potential difference is formed, which produces a physiological effect of stimulating the contraction of the cell membrane. Cardiomyocytes contract and pump calcium ions out of the cell membrane, forming a reverse potential difference. Under the action of this reverse potential difference, the cardiomyocyte membrane begins to relax; after relaxation, the permeability of the cell membrane increases, and calcium ions Once again, it passes through the cell membrane and enters the cardiomyocytes, causing the myocardium to contract again, so that the heart beats rhythmically.

The mechanism of transmitting anti-enemy signals is: foreign antigens activate T cell receptors, start calcium ion-mediated signaling pathways, and promote immune cell differentiation and growth. When foreign invaders such as germs, bacteria, and poisons invade the human body, it is calcium ions that first send out an early warning signal; then calcium ions send out a signal of the characteristics of the invader, and the immune system organizes corresponding immune cells to capture and engulf the enemy. Once calcium is deficient, the function of the immune system will decline, become disordered, and cause diseases. Such as: autoimmune diseases lupus erythematosus, rheumatism; skin diseases: dermatitis, acne, etc. Calcium supplementation plays an important role in the treatment of these diseases, which proves the function of calcium. Regulate the activity of enzymes, the mechanism is: Calcium regulatory protein in the cell combines with calcium ions to form a complex, which can activate the activities of various enzymes in the body. If the skin is cut and bleeding occurs, calcium ions immediately send a signal to activate thrombin step by step and start the coagulation mechanism to stop the bleeding. Nutrients in food can be absorbed by the human body only through the decomposition of enzymes, while protease, lipase, amylase, ATPase and other enzymes and hormones can be fully active only through the action of calcium ions, so nutrition has " Calcium supplementation is the source of all nutrients.” Regulating the maturation and fertilization of germ cells, the mechanism is: the front end of sperm DNA is an acrosome composed of calcium. The front end of the DNA carried by the sperm is an acrosome composed of calcium. It is this calcium acrosome that enables the sperm to destroy and penetrate the inner membrane of the egg cell when it reaches the edge of the egg cell, and the moment of fertilization happens like this. At the same time waves made of calcium surround the egg cell, known as calcium oscillations. Calcium oscillation plays a role in activating the egg, so that the egg can obtain the ability to fertilize, and the gestation of a life begins from then on. Therefore, if calcium is not sufficient, it will directly affect human sexual function and sperm motility, leading to infertility.

Recent studies have found that calcium is involved in a wider range of physiological processes, such as the control of cell excitability, cell metabolism, maintenance of cell shape, regulation of cell cycle, etc. Calcium ions can activate enzymes related to signal transduction, mainly in the following aspects: 1. The distribution of calcium ions in cells has obvious regional characteristics, and the free calcium concentration in extracellular fluid is much higher than that in intracellular calcium. More than 90% of the calcium ions in the cell are stored in the intracellular calcium pool (in the endoplasmic reticulum and mitochondria), and the calcium concentration in the cytoplasm is very low. If the calcium channel of the plasma membrane or the intracellular calcium store is opened, it will cause the inflow of extracellular calcium or the release of calcium from the intracellular calcium store, which will cause a sharp increase in the concentration of calcium ion in the cytoplasm. After calcium ions enter the cytoplasm, they can return to the extracellular or intracellular calcium pool through the calcium pump (calcium ion-ATPase) on the cytoplasmic membrane and calcium store membrane to maintain the low calcium state in the cytoplasm. 2. The downstream signal transduction molecule of calcium ions is calmodulin. Calmodulin (CaM) is a calcium-binding protein with 4 structural domains in the molecule, and each domain can bind 1 calcium ion. When the concentration of calcium ions in the cytoplasm is low, calmodulin is not easy to bind calcium ions; as the concentration of calcium ions in the cytoplasm increases, calmodulin can bind different amounts of calcium ions to form calcium ion/calmodulin complexes in different conformations thing. Calmodulin itself is inactive, and has a regulatory function after forming a calcium ion/calmodulin complex, which can regulate the activity of calmodulin-dependent protein kinase. 3. Calmodulin is not the only target molecule of calcium ions. In addition to calmodulin, calcium ions also bind to various signal transduction molecules such as PKC, AC and cAMP-PDE, and activate these molecules through allosteric effects

Chondroitin sulfate (CHONDROITIN SULFATE, CS) is a type of glycosaminoglycan covalently linked to proteins to form proteoglycans. Chondroitin sulfate is widely distributed in the extracellular matrix and cell surface of animal tissues. The sugar chain is composed of alternating glucuronic acid and N-acetylgalactosamine (also known as N-acetylgalactosamine) disaccharide units. The linking region is linked to a serine residue of the core protein. Chondroitin sulfate is present in all organisms from nematodes to humans except plants, where it performs many important physiological functions. Although the main chain structure of the polysaccharide is not complex, it shows a high degree of heterogeneity in terms of the degree of sulfation, the distribution of sulfate groups, and the distribution of the two differences into the chain of the isomeric uronic acid. The fine structure of chondroitin sulfate determines the specificity of function and interaction with various protein molecules. In 1956, Meyer et al. first began to study the types and contents of acidic mucopolysaccharides in different tissues, and identified the presence of CS, hyaluronic acid, keratan sulfate and other mucopolysaccharides in connective tissue. The unsaturated sugars produced by CS under acidic, alkaline and enzymatic conditions, including low-molecular CS and oligosaccharides or disaccharides of CS, are all related to β-elimination reactions. The degree of degradation of CS under acidic, alkaline and neutral conditions is expressed by the UV absorbance value at 232nm. The larger the UV absorbance value, the greater the degradation degree, which reflects the stability of CS under different conditions. CS is an acidic mucopolysaccharide extracted from animal tissues, which is white or off-white powder; odorless; hygroscopic. The aqueous solution of this product is viscous and will not condense when heated. This product is easily soluble in water, insoluble in organic solvents such as ethanol, acetone, and ether, and its salts are relatively stable to heat, and will not be destroyed when heated up to 80°C. The aqueous solution of chondroitin sulfate is unstable in case of higher temperature or acid, mainly deacetylated or degraded into monosaccharide or polysaccharide with smaller molecular weight. The main application of chondroitin sulfate in medicine is as a medicine for the treatment of joint diseases. When used in conjunction with glucosamine, it has the effect of relieving pain and promoting cartilage regeneration, which can fundamentally improve joint problems. Randomized placebo-controlled clinical trials have demonstrated that chondroitin sulfate can reduce pain in patients with osteoarthritis, improve joint function, reduce joint swelling and fluid accumulation and prevent gap narrowing in the knee and hand joints. Provide cushioning effect, ease the impact and friction during movement, absorb water into proteoglycan molecules, thicken cartilage, and increase the amount of synovial fluid in joints. One of the important functions of chondroitin is to serve as a pipeline to transport important oxygen supply and nutrients to the joints, help remove waste in the joints, and remove carbon dioxide and waste at the same time. Since articular cartilage has no blood supply, all oxygenation, nourishment and lubrication comes from synovial fluid. Chondroitin sulfate has a protective effect on corneal collagen fibers, can promote the growth of fibers in the matrix, enhance permeability, improve blood circulation, accelerate metabolism, promote the absorption of permeate and eliminate inflammation; its polyanion has strong water retention, It can improve the moisture metabolism of the cornea tissue, has a strong affinity for the cornea, can form a breathable water-retaining film on the surface of the cornea, and improve the symptoms of eye dryness. By promoting the formation of matrix, it provides a framework for cell migration, which is beneficial to the migration of corneal epithelial cells, thereby promoting the healing of corneal wounds, the absorption of exudate and the elimination of inflammation. Through high-tech deep processing, it can treat neuropathic headache, trigeminal neuralgia, coronary heart disease, angina pectoris, myocardial hypoxia, cardiovascular and cerebrovascular diseases, arthralgia, atherosclerosis and hepatitis, among which CS also has anticoagulant and antithrombotic properties It can also be used for adjuvant treatment of hearing impairment and liver function damage caused by streptomycin, as well as adjuvant treatment of hyperlipidemia. It can be used as a health care product and an additive in food, and has the functions of enhancing human body physique, anti-bacteria, beautifying, and anti-aging. Improve hearing and dry skin. In the body, it can inhibit the absorption of lipids and glucose in the small intestine to achieve weight loss.

Chondroitin sulfate is widely found in human and animal cartilage tissue. Its medicinal preparation mainly contains two isomers of chondroitin sulfate A and chondroitin sulfate C, and the content of chondroitin sulfate in cartilage of different species and ages is different. Its pharmacological effects are as follows: 1. CS can remove lipids and lipoproteins in the blood in the body, remove cholesterol in blood vessels around the heart, prevent and treat atherosclerosis, and increase the conversion rate of lipids and fatty acids in cells. 2. CS can effectively prevent and treat coronary heart disease. It has anti-atherosclerosis and anti-atherosclerotic plaque formation effects on experimental arteriosclerosis models; it can increase the coronary artery branch or collateral circulation of atherosclerosis, and can accelerate the development of experimental coronary arteriosclerosis or embolism. Healing, regeneration and repair of myocardial necrosis or degeneration. 3. It can increase the biosynthesis of messenger ribonucleic acid (mRNA) and deoxyribonucleic acid (DNA) in cells and has the effect of promoting cell metabolism. 4. Low anticoagulant activity. Chondroitin sulfate has a moderate anticoagulant effect, and every 1mg of chondroitin sulfate A is equivalent to the anticoagulant activity of 0.45U heparin. This anticoagulant activity does not depend on antithrombin III, it can exert anticoagulant activity through the fibrinogen system. 5. Chondroitin sulfate also has anti-inflammatory, accelerated wound healing and anti-tumor effects. The long-term clinical application of chondroitin sulfate has found that the fat and other lipids deposited on the walls of arteries and veins can be effectively removed or reduced, and can significantly reduce plasma cholesterol, thereby preventing the formation of atherosclerosis. Chondroitin sulfate is used for the treatment of neuralgia, neuropathic migraine, joint pain, arthritis, scapular joint pain, pain after abdominal surgery, etc. The prevention and treatment of hearing impairment caused by streptomycin and hearing difficulties and tinnitus caused by various noises have remarkable effects. It has auxiliary therapeutic effect on chronic nephritis, chronic hepatitis, keratitis and corneal ulcer. Chondroitin in shark cartilage has anti-tumor effect. In addition, chondroitin sulfate is also used in cosmetics and wound healing agents. Chondroitin sulfate is an acidic mucopolysaccharide, which is one of the important components in eye tissue. It can promote and improve corneal water metabolism, and is suitable for visual fatigue and dry eye. Chondroitin sulfate can effectively improve bone quality. By increasing the supply of chondroitin sulfate, the body's self-regulating mechanism is inhibited, bone hardening is reduced, and firm and flexible bones are 10% smaller in volume than fragile bones, and their strength is greatly enhanced. Especially the facial contour, it is not easy to deform or expand, and the tissue adhesion is improved. Contour bone process reduction trend, restore youthful state. It is important to also take chondroitin when taking glucosamine because chondroitin facilitates the process of glucosamine infiltration into the joints. A number of studies have shown that, including one published in the New England Journal of Medicine, the CINEFL research institute pointed out that the combined intake of glucosamine and chondroitin can more effectively protect, reverse damage and promote the repair of articular cartilage and membranous bone, making bone harden Reduced, so that the bones appear youthful. It is important to also take chondroitin when taking glucosamine because chondroitin facilitates the process of glucosamine infiltration into the joints. Chondroitin sulfate can also inhibit cartilage-destroying enzymes (such as collagenase, elastase, and cathepsin), preventing cartilage from being broken down or dissolved, or hardened. It can start from the root of the problem and inhibit the activity of COX-2 to stop joint inflammation.

Casein Phosphopeptides (CPP for short) are biologically active peptides made from bovine milk casein through biotechnology. The CPP molecule is composed of twenty to thirty amino acid residues, including 4 to 7 clustered phosphosilyl groups. A large number of experiments have proved that CPP can effectively promote the body's absorption and utilization of divalent mineral nutrients such as calcium, iron, and zinc. Casein phosphopeptides can be used in various nutritional and health foods, and can effectively promote the absorption and utilization of calcium, iron, zinc and other divalent mineral nutrients by the human body. Casein phosphopeptide is made from casein hydrolyzed by trypsin or trypsin, refined and purified, and its core structure is: -Ser(P)-Ser(P)-Ser(P)-Glu-Glu-(Ser : Serine, Glu: Glutamic acid, P: Phosphate group). Phosphoserine residues (-Ser(P)-) in this structure exist in clusters, which are negatively charged in the weakly alkaline environment of intestinal pH, which can prevent the further action of digestive enzymes, so that CPP will not be further hydrolyzed and Stable in the intestine. Domestic studies have found that the smaller the molar ratio of nitrogen to phosphorus in CPP, the shorter the peptide chain of CPP and the greater the density of phosphate groups, the higher the purity of CPP and the stronger the effect of promoting calcium absorption and utilization. Calcium is easily absorbed only when it exists in the form of ions, and it is easy to form insoluble salts with acid radical ions and lose in neutral and weakly alkaline environments. The absorption of calcium by CPP is mainly manifested in that it can combine with calcium in a neutral and weakly alkaline environment, inhibit the formation of insoluble precipitates, avoid the loss of calcium, and finally passively absorb due to the increase in the concentration of free calcium. Current studies have shown that the role of CPP in promoting calcium absorption is mainly manifested in the following aspects: to promote the absorption of calcium in the small intestine, the cereals in the human diet contain a large amount of high phosphorus components such as phytic acid and phytic acid, and in the lower small intestine Combined with calcium in pH7~8 environment to form calcium phosphate precipitate. CPP can inhibit the formation of calcium phosphate precipitates, maintain a high concentration of free calcium, promote the passive absorption of calcium, and become another way for vitamin D to act as a calcium absorption enhancer. Promote the utilization of calcium by bones. Animal experiments have shown that CPP can promote the absorption and utilization of calcium, weaken the action of osteoclasts and inhibit bone reabsorption. Promote the utilization of calcium by teeth. In the past, it was believed that chewing cheese after a meal can stimulate the secretion of saliva, so that the alkaline saliva can buffer the corrosion of the enamel by the acidic substances on the plaque, and help prevent the occurrence of dental caries. In recent years, studies have found that CPP contained in cheese can bind calcium ions in food to dental caries, reduce the demineralization of enamel, and thus achieve the purpose of anti-caries. Studies have found that the sperm in the culture medium containing CPP has a significantly higher ability to penetrate egg cells, and can also reduce the degree of variation of sperm and make embryo development more stable. CPP can also improve the bioavailability of iron, zinc, magnesium and other metal ions, so it is called a peptide substance with metal carrier function. At present, CPP has been applied to food and health products such as children's curry rice, beverages, and chewing gum abroad. Research and application on calcium deficiency in children, osteoporosis in the elderly, treatment of infertility and dental care are also in progress. Because CPP is a polypeptide extracted from natural proteins, it has the advantages of less adverse reactions, safety and reliability, and thus will be more widely used. The sensitization of casein, skimmed milk protein and CPP has been studied abroad, and it is found that the sensitization of CPP is very small, indicating that it can be applied to those who are allergic to milk. However, it should also be noted that the factors affecting the function of CPP are very complex, and the role in the process of calcium metabolism needs to be further studied. Casein phosphopeptides can chelate calcium, iron, zinc ions and protect them from being precipitated by anions such as phosphoric acid, oxalic acid, and phytic acid in the diet, thus effectively Promote the absorption and utilization of calcium, iron, zinc, etc. CPP is also a new product developed with an eye on improving the absorption and utilization of calcium. Compared with the traditional calcium absorber vitamin D, CPP has the following characteristics: 1. In addition to promoting calcium absorption, CPP can also promote iron, zinc, etc. Absorption of divalent mineral nutrients. Iron and zinc are the minerals that Chinese people are most likely to lack besides calcium. Simple and excessive calcium supplementation will have a certain impact on the absorption of iron and zinc. If CPP is added to calcium, iron, zinc-fortified nutritional foods or nutritional health products, it will not only increase the absorption of calcium, but also improve the absorption and utilization of iron and zinc, thereby effectively overcoming the general calcium supplements’ effects on iron, iron, and zinc. Potential adverse effects on zinc absorption, a property not found in any other calcium supplement. 2. Vitamin D can promote the active transport and absorption of saturable calcium in the upper small intestine, and the effect of vitamin D is affected by age and calcium intake; CPP can passively diffuse unsaturated absorption in the lower small intestine, and this absorption is not affected by age and calcium intake. The influence of calcium intake changes, while the passive diffusion absorption of calcium is much greater than the active transport absorption. CPP products also have good stability, and the shelf life can reach more than 18 months under dry and dark conditions. After being added to the product, it has good stability in the acidic to neutral range, and can withstand high temperature treatment at 120 degrees for 30 minutes. Under alkaline conditions, the stability is poor. With the increase of heating temperature and heating time, the dephosphorylation reaction will be intensified, and the function of CPP will be affected. Under normal use conditions, the structure and function of CPP are stable. 3. Fortifying VD in diet can increase calcium absorption, but excessive intake of VD will cause certain harm to kidney and bone. However, if a certain amount of CPP is added to the diet while calcium is fortified, the calcium in the intestinal tract can be kept in a dissolved state, thereby effectively promoting the absorption and utilization of calcium, and CPP is derived from milk protein, so even if taken in excess, it will not Will have any toxic side effects on the human body. In addition, CPP has the characteristics of being completely soluble in a wide pH range, can withstand high temperature treatment, and has good stability. When CPP is added to food, it has the characteristics of low-volume and high-efficiency. Products added with CPP can maintain the original Flavor and texture. The calcium holding capacity of CPP refers to the amount of calcium held in solution by CPP under certain conditions. In the solution system with calcium ions and phosphate radicals, when the pH is alkaline, calcium phosphate precipitates will form. The presence of CPP can reduce the loss of calcium caused by calcium phosphate precipitation, so that more calcium remains dissolved. When Ca:P=1:1 (8mM:8Mm) and 2:1 (12Mm:6Mm), 200ppm of CPP was added to the system and incubated at 35°C for 1 hour. When Ca:P=1:1 and 2:1, the calcium holding capacity of CPP (expressed as the number of moles of dissolved calcium per mole of organic phosphorus in the CPP molecule) is 37.2 and 28.0, respectively. In terms of CPP preventing osteoporosis, the animal model used in the animal experiment is ovariectomized aged female rats. Adding CPP in the feed is the test group, and series 2 is the control group without CPP in the feed. When the test was carried out to 4 months, the relative bone mineral density of the test group was significantly higher than that of the control group, indicating that CPP has a good effect in preventing bone loss in aged female rats. CPP has a moderate combination with calcium, such a binding strength can protect calcium ions from being precipitated, and is enough to promote the transport of a large amount of dissolved calcium to the intestinal mucosa without affecting calcium absorption due to too tight binding. The combination of CPP and calcium is dynamic. Calcium ions are constantly combined and released by CPP, recombined and released again, so that a phosphate group in the CPP molecule can protect more than 30 calcium ions from being precipitated.

Scientific research has proved that under normal circumstances, the absorption rate of various calcium sources is almost the same. The reason why milk is well-known and the favorite calcium supplement food of human beings is not only that milk is rich in calcium, but also because milk enzyme protein can generate part of CPP through the action of intestinal protease in the body, and CPP can promote the absorption and utilization of calcium In other words, the absorption rate should not be the basis for manufacturers to choose calcium sources. It is wise to add an appropriate amount of calcium absorption promoter CPP to the product. CPP is a product extracted from casein in milk through biotechnology. It is a veritable "natural milk essence". Therefore, it is most suitable to add CPP to calcium supplement products.

CPP has the characteristics of being completely soluble in a wide pH range, can withstand high temperature treatment, and has good stability. Therefore, it can be added to the following products: Nutrition and health products fortified with calcium, iron, and zinc Milk Nutritious foods for children, such as infant nutrition rice noodles, high-calcium biscuits, etc. Soy products, such as high-calcium soybean milk powder, calcium tofu, etc. Nutritious oatmeal, chewing gum, etc. Toothpaste for tooth decay prevention, beer, sparkling wine and other gas-containing beverages (which can make the foam delicate and long-lasting, and promote the absorption of minerals in it) When applied to the above products, CPP can make the product formula more perfect, reasonable, and truly The purpose of supplementing these mineral nutrients to the human body can be achieved, and at the same time, the upgrading of the original products can also be realized. In addition, the original flavor and taste of products added with CPP can remain unchanged. All of the above products have added CPP to the products fortified with calcium and iron, making them different from other similar products in the market and taking a leading position in the market. CPP can not only promote the absorption of calcium, but also has a good effect on the absorption and utilization of iron and zinc. Therefore, the development of nutritious food and health products added with CPP can truly achieve the purpose of effectively supplementing the minerals that the human body lacks and meet people's nutritional needs, and will certainly produce huge economic and social benefits. Casein phosphopeptides are derived from natural high-quality protein --- cow milk casein, which can effectively increase the intake, absorption and utilization of divalent minerals such as calcium, iron, zinc, etc. The role of gingiva. CPP is also a new type of nutritional product developed with an eye on improving the absorption and utilization of calcium. It is one of the bioactive peptide food additives that has been industrialized so far. Compared with VD, it has a higher absorption rate and no side effects. It can also improve the absorption rate of other divalent minerals such as zinc and iron. CPP can promote passive diffusion absorption of unsaturated calcium in the lower small intestine, which is not affected by age and VD.

In the composition of the present invention, it has been unexpectedly found that adding a small amount of glyceryl behenate together with chondroitin sulfate can significantly improve the stability of puerarin, an important active ingredient, and it has been found through experiments that the stability of puerarin is affected by The effect of chondroitin sulfate. The specific method and result of this improving the stability of puerarin are as follows: referring to Example 1～Example 5 respectively, the difference is that in step (1), glyceryl behenate is also added together with chondroitin sulfate (each example adds Amount is equivalent to 20%, 25%, 15%, 18%, 22% of chondroitin sulfate weight respectively), obtains 5 batches and can be referred to as the tablet of supplementary example a1～supplementary example a5 respectively; Make embodiment 1～implementation Tablets of Example 5 and Supplementary Example a1 to Supplementary Example a5 were placed at a temperature of 40°C for 6 months, and each batch of tablets was determined using the [Content Determination] method of Radix Puerariae on page 333 of the 2015 edition of "Chinese Pharmacopoeia". Puerarin content in the tablet at 0 months and 6 months; for each sample, the puerarin residual percentage is calculated according to the following formula: puerarin residual percentage = 6 puerarin content ÷ 0 puerarin content × 100% Result, the puerarin residual percentage of embodiment 1～embodiment 5 tablet is 90.6%～92.2%, the puerarin residual percentage of supplementary example a1～supplementary example a5 tablet is 98.8%～99.6%, the latter shows higher than The former shows that the important physiologically active substance puerarin in the latter tablet is obviously more stable; in addition, with reference to Examples 1 to 5, the difference is that chondroitin sulfate is not added to the prescription, and 5 batches can be called respectively. For the tablets of Supplementary Example b1 to Supplementary Example b5, these five batches of tablets were treated at 40°C-6 months by the same method as above, and the residual puerarin percentage was measured and calculated in June, and the result was that their puerarin residual percentage was 98.1% ~99.3%. This shows that the obvious reduction of puerarin content in Examples 1 to 5 is due to the adverse effect of chondroitin sulfate, and this adverse effect can be overcome by adding glyceryl behenate, a conventional pharmaceutical excipient in the art. Therefore, according to any aspect of the present invention, wherein glyceryl behenate is also added. In one embodiment, the added amount of glyceryl behenate is equivalent to 15%-25% of the weight of chondroitin sulfate. In one embodiment, glyceryl behenate is added with chondroitin sulfate.

The traditional Chinese medicine composition for improving bone density, improving bone and joint function, avoiding or reducing waist and leg cramps for middle-aged and elderly people of the present invention is made of kudzu root extract, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate, and casein phosphopeptide . The combined biological effects of these medicinal materials are presented, especially the effects of significantly increasing bone density, improving bone and joint functions, and avoiding or reducing waist and leg cramps. For example, for 36 subjects with low bone density, each person was given 10 g of the composition obtained in Example 1 of the present invention every day, and was taken twice in the morning and evening. After 2 months, the bone density of all subjects increased by more than 23% to 23.3 % to 27.6% range. This shows that the combination of the present invention has an excellent effect of increasing bone density, and these subjects reported obvious improvement in bone and joint function after 2 months. For another example, for 48 subjects who had leg cramps more than 3 times in the past 1 month, each person was given 10 g of the composition obtained in Example 1 of the present invention every day, taking it twice in the morning and evening, and continued taking it for 2 weeks. Within 2 months of the test, none of the subjects had leg cramps.

In addition, based on the physiological properties of various medicinal materials in the traditional Chinese medicine composition used to improve bone density, improve bone and joint function, and avoid or reduce waist and leg cramps for middle-aged and elderly people, it is fully expected that the present invention can be used for middle-aged and elderly people. The traditional Chinese medicine composition for improving bone density, improving bone and joint function, and avoiding or reducing waist and leg cramps can present the biological effects produced by these medicinal materials individually or in combination. For example, the traditional Chinese medicine composition of the present invention for improving bone density, improving bone and joint function, avoiding or reducing waist and leg cramps for middle-aged and elderly people can be endowed with kudzu root, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate, casein phosphopeptide as above The respective typical biological effects described. Therefore, the use of the third aspect of the present invention also includes the use related to the above-mentioned therapeutic/preventive effects.

Detailed ways

The present invention can be further described by the following examples, however, the scope of the present invention is not limited to the following examples. Those skilled in the art can understand that various changes and modifications can be made in the present invention without departing from the spirit and scope of the present invention. The present invention provides general and/or specific descriptions of the materials and test methods used in the tests. While many of the materials and methods of manipulation which are employed for the purposes of the invention are well known in the art, the invention has been described here in as much detail as possible.

Each batch of total charge in the following compositions is 10 kg.

Embodiment 1: preparation of Chinese medicine composition

Formula: 500 parts by weight of kudzu root extract, 440 parts by weight of glucosamine hydrochloride, 400 parts by weight of calcium carbonate, 100 parts by weight of chondroitin sulfate, 25 parts by weight of casein phosphopeptide, 760 parts by weight of xylitol, and 250 parts by weight of microcrystalline cellulose part, 25 parts by weight of magnesium stearate.

Preparation method:

(1) make Pueraria root extract and glucosamine hydrochloride mix uniformly, make calcium carbonate and chondroitin sulfate mix uniformly in addition;

(2) dissolving the casein phosphopeptide in 6 times the amount of water, then adding xylitol 2.5 times the weight of the casein phosphopeptide, and mixing evenly, allowing the mixture to be ventilated for 2.75 hours at a temperature of 65° C., and mixing evenly;

(3) Mix the various mixtures obtained in the above two steps, add microcrystalline cellulose and the remaining amount of xylitol to it, mix well, add water as a lubricant, prepare wet granules, and dry the wet granules;

(4) Mix the dried granules obtained in the previous step with magnesium stearate to obtain the composition, which is further compressed into tablets, 2.5 grams per tablet, which is a chewable tablet.

Embodiment 2: preparation of Chinese medicine composition

Formula: 500 parts by weight of kudzu root extract, 400 parts by weight of glucosamine hydrochloride, 500 parts by weight of calcium carbonate, 50 parts by weight of chondroitin sulfate, 40 parts by weight of casein phosphopeptide, 600 parts by weight of xylitol, and 280 parts by weight of microcrystalline cellulose part, 22 parts by weight of magnesium stearate.

Preparation method:

(1) make Pueraria root extract and glucosamine hydrochloride mix uniformly, make calcium carbonate and chondroitin sulfate mix uniformly in addition;

(2) Dissolve the casein phosphopeptide in 7 times the amount of water, then add xylitol twice the weight of the casein phosphopeptide, mix well, make the mixture ventilated at 65°C for 2.75 hours, and mix well;

(3) Mix the various mixtures obtained in the above two steps, add microcrystalline cellulose and the remaining amount of xylitol to it, mix well, add water as a lubricant, prepare wet granules, and dry the wet granules;

(4) Mix the dried granules obtained in the previous step with magnesium stearate to obtain the composition, which is further compressed into tablets, 2.5 grams per tablet, which is a chewable tablet.

Embodiment 3: preparation of Chinese medicine composition

Formula: 500 parts by weight of kudzu root extract, 500 parts by weight of glucosamine hydrochloride, 300 parts by weight of calcium carbonate, 150 parts by weight of chondroitin sulfate, 10 parts by weight of casein phosphopeptide, 900 parts by weight of xylitol, 220 parts by weight of microcrystalline cellulose part, 28 parts by weight of magnesium stearate.

Preparation method:

(1) make Pueraria root extract and glucosamine hydrochloride mix uniformly, make calcium carbonate and chondroitin sulfate mix uniformly in addition;

(2) Dissolve the casein phosphopeptide in 8 times the amount of water, then add xylitol 3 times the weight of the casein phosphopeptide, mix well, make the mixture ventilated at 60°C for 3 hours, and mix well;

(3) Mix the various mixtures obtained in the above two steps, add microcrystalline cellulose and the remaining amount of xylitol to it, mix well, add water as a lubricant, prepare wet granules, and dry the wet granules;

(4) Mix the dried granules obtained in the previous step with magnesium stearate to obtain the composition, which is further compressed into tablets, 2.5 grams per tablet, which is a chewable tablet.

Embodiment 4: prepare Chinese medicine composition

Formula: 500 parts by weight of kudzu root extract, 470 parts by weight of glucosamine hydrochloride, 350 parts by weight of calcium carbonate, 125 parts by weight of chondroitin sulfate, 20 parts by weight of casein phosphopeptide, 800 parts by weight of xylitol, 240 parts by weight of microcrystalline cellulose part, 26 parts by weight of magnesium stearate.

Preparation method:

(1) make Pueraria root extract and glucosamine hydrochloride mix uniformly, make calcium carbonate and chondroitin sulfate mix uniformly in addition;

(2) dissolving the casein phosphopeptide with 5 times the amount of water, then adding xylitol with 2.5 times the weight of the casein phosphopeptide, and mixing evenly, allowing the mixture to be ventilated for 2.5 hours at a temperature of 70° C., and mixing evenly;

(3) Mix the various mixtures obtained in the above two steps, add microcrystalline cellulose and the remaining amount of xylitol to it, mix well, add water as a lubricant, prepare wet granules, and dry the wet granules;

(4) Mix the dried granules obtained in the previous step with magnesium stearate to obtain the composition, which is further compressed into tablets, 2.5 grams per tablet, which is a chewable tablet.

Embodiment 5: preparation of Chinese medicine composition

Formula: 500 parts by weight of kudzu root extract, 420 parts by weight of glucosamine hydrochloride, 450 parts by weight of calcium carbonate, 75 parts by weight of chondroitin sulfate, 30 parts by weight of casein phosphopeptide, 700 parts by weight of xylitol, and 260 parts by weight of microcrystalline cellulose 24 parts by weight of magnesium stearate.

Preparation method:

(1) make Pueraria root extract and glucosamine hydrochloride mix uniformly, make calcium carbonate and chondroitin sulfate mix uniformly in addition;

(2) Dissolve the casein phosphopeptide in 6 times the amount of water, then add xylitol with 2.3 times the weight of the casein phosphopeptide, mix well, make the mixture ventilated at 65°C for 2.5 hours, and mix well;

(3) Mix the various mixtures obtained in the above two steps, add microcrystalline cellulose and the remaining amount of xylitol to it, mix well, add water as a lubricant, prepare wet granules, and dry the wet granules;

(4) Mix the dried granules obtained in the previous step with magnesium stearate to obtain the composition, which is further compressed into tablets, 2.5 grams per tablet, which is a chewable tablet.

It will be apparent to those skilled in the art that the invention is not limited to the details of the above-described exemplary embodiments, but that the invention can be embodied in other specific forms without departing from the spirit or essential characteristics of the invention. Accordingly, the embodiments should be regarded in all points of view as exemplary and not restrictive, the scope of the invention being defined by the appended claims rather than the foregoing description, and it is therefore intended that the scope of the invention be defined by the appended claims rather than by the foregoing description. All changes within the meaning and range of equivalents of the elements are embraced in the present invention.

Claims (10)

1. the composition for avoiding waist-leg from knotting for improving middle-aged and the old's bone density and osteoarticular function comprising：Pueraria lobata extracts Object, aminoglucose hydrochloride, calcium carbonate, chondroitin sulfate, casein phosphopeptide and the acceptable load of optional physiology Body.

2. composition according to claim 1 comprising 500 parts by weight of kudzu root extract, aminoglucose hydrochloride 400~500 Parts by weight, 300~500 parts by weight of calcium carbonate, 50~150 parts by weight of chondroitin sulfate, 10~40 parts by weight of casein phosphopeptide, And the optional acceptable carrier of physiology.

3. composition according to claim 1 comprising 500 parts by weight of kudzu root extract, aminoglucose hydrochloride 400~500 Parts by weight, 300~500 parts by weight of calcium carbonate, 50~150 parts by weight of chondroitin sulfate, 10~40 parts by weight of casein phosphopeptide, And the optional acceptable carrier of physiology.

4. composition according to claim 1 comprising 500 parts by weight of kudzu root extract, aminoglucose hydrochloride 420~470 Parts by weight, 350~450 parts by weight of calcium carbonate, 75~125 parts by weight of chondroitin sulfate, 20~30 parts by weight of casein phosphopeptide, And the optional acceptable carrier of physiology.

5. composition according to claim 1 comprising 500 parts by weight of kudzu root extract, 440 weight of aminoglucose hydrochloride Part, 400 parts by weight of calcium carbonate, 100 parts by weight of chondroitin sulfate, 25 parts by weight of casein phosphopeptide and optional physiology Acceptable carrier.

6. composition according to claim 1, in the form of tablet or granule；Alternatively, it is the tablet form of chewable tablets.

7. composition according to claim 1, it is characterised in that：

In the form of tablet, the acceptable carrier of physiology includes xylitol, microcrystalline cellulose, magnesium stearate for it；

It is in the form of tablet, and in terms of every 500 parts by weight kudzu root extract, the amount of xylitol is 500~1000 parts by weight, such as 600~900 parts by weight, such as 700~800 parts by weight, such as 760 parts by weight；

It is in the form of tablet, and in terms of every 500 parts by weight kudzu root extract, the amount of microcrystalline cellulose is 200~300 parts by weight, Such as 220~280 parts by weight, such as 240~260 parts by weight, such as 250 parts by weight；Or

It is in the form of tablet, and in terms of every 500 parts by weight kudzu root extract, the amount of magnesium stearate is 20~30 parts by weight, such as 22~28 parts by weight, such as 24~26 parts by weight, such as 25 parts by weight.

8. composition according to claim 1 is prepared according to the method included the following steps：

(1) it is uniformly mixed kudzu root extract with aminoglucose hydrochloride, is separately uniformly mixed calcium carbonate and chondroitin sulfate；

(2) so that casein phosphopeptide is added the water dissolution of 5~8 times of amounts, add 2~3 times of casein phosphopeptide weight of xylitol, It is uniformly mixed, makes this mixture ventilation process 2.5~3 hours at a temperature of 60~70 DEG C, be uniformly mixed；

(3) various mixtures obtained by both the above step are mixed, add the xylitol of microcrystalline cellulose and surplus thereto, It is uniformly mixed, adding water is lubricant, prepares wet granular, keeps wet granular dry；

(4) it is uniformly mixed dry particle obtained by previous step with magnesium stearate, composition is obtained, as granular preparation shape Formula is directly packed, or is further pressed into tablet, obtains the dosage form of granule or tablet.

9. the method for preparing the composition of any one of claim 1~8, includes the following steps：

(1) it is uniformly mixed kudzu root extract with aminoglucose hydrochloride, is separately uniformly mixed calcium carbonate and chondroitin sulfate；

(2) so that casein phosphopeptide is added the water dissolution of 5~8 times of amounts, add 2~3 times of casein phosphopeptide weight of xylitol, It is uniformly mixed, makes this mixture ventilation process 2.5~3 hours at a temperature of 60~70 DEG C, be uniformly mixed；

(3) various mixtures obtained by both the above step are mixed, add the xylitol of microcrystalline cellulose and surplus thereto, It is uniformly mixed, adding water is lubricant, prepares wet granular, keeps wet granular dry；

(4) it is uniformly mixed dry particle obtained by previous step with magnesium stearate, composition is obtained, as granular preparation shape Formula is directly packed, or is further pressed into tablet, obtains the dosage form of granule or tablet.

10. the composition of any one of claim 1~8 preparation for improve middle-aged and the old's bone density, osteoarticular function and The purposes in product for avoiding waist-leg from knotting.