CN108815505B - Composition for improving bone density and bone joint function of middle-aged and elderly people and avoiding lumbar and leg cramps - Google Patents

Composition for improving bone density and bone joint function of middle-aged and elderly people and avoiding lumbar and leg cramps Download PDF

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CN108815505B
CN108815505B CN201810705237.8A CN201810705237A CN108815505B CN 108815505 B CN108815505 B CN 108815505B CN 201810705237 A CN201810705237 A CN 201810705237A CN 108815505 B CN108815505 B CN 108815505B
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傅金荣
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Abstract

The invention relates to a composition for improving bone density and bone joint function of middle-aged and elderly people and avoiding cramping of waist and legs. The composition is prepared from 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, 10-40 parts by weight of casein phosphopeptide and optional physiologically acceptable carriers. Experiments prove that the composition has excellent effects of improving the bone mineral density of middle-aged and elderly people, enhancing the function of bone joints and avoiding cramping of waist and legs. The invention also relates to a preparation method of the composition and application of the composition in preparing products for improving bone density and bone joint functions of middle-aged and elderly people and preventing cramps in waist and legs.

Description

Composition for improving bone density and bone joint function of middle-aged and elderly people and avoiding lumbar and leg cramps
Technical Field
The invention belongs to the technical field of medical health-care products, relates to a traditional Chinese medicine composition for improving bone density, improving bone joint function and avoiding or reducing cramp of waist and legs for middle-aged and elderly people, also relates to a preparation method of the composition and medical applications of the composition, and more particularly relates to a composition prepared from casein and kudzu root.
Background
The middle-aged and the elderly suffer from bone density loss of different degrees, and the related physiological manifestations are bone joint function reduction and frequent occurrence of cramps in waist and legs.
Bone Mineral Density (BMD), which is an important indicator of bone strength, is an absolute value in grams per cubic centimeter. When the bone density value is clinically used, the T value is usually used to judge whether the bone density is normal or not because the absolute values of different bone density detectors are different. The value of T is a relative value, and the normal reference value is between-1 and + 1. Abnormal when T is less than-2.5. Bone density is an important mark of bone quality, reflects the osteoporosis degree and is an important basis for predicting fracture risk. Due to the increasing improvement of the measuring method and the development of advanced software, the method can be used for different parts, and the measuring precision is obviously improved. Besides the diagnosis of osteoporosis, the method can be used for clinical pharmacodynamic observation and epidemiological investigation, and has obvious superiority in the aspect of predicting osteoporotic fracture. The bone density value of Chinese northern Han healthy people is determined by the age and size of peak bone density and the normal value of each age group. DXA was used to measure lumbar vertebrae L2- -L4 and hip bone density. The results show that the peak bone density of men is 20-24 years old at all ages, and the density value of L2-L4 is 1.228(g/cm 3); the peak age of women is 30-34 years of lumbar spine and the value is 1.197(g/cm 3). The peak age of hip bone density is 25-29 years old. In the world osteoporosis congress of 2004, the International Foundation for Osteoporosis (IFO), John's institute for metabolic bone disease, WHO, university of Sheffield, John, et al, performed meta-analysis of 12 clinical studies, and it was suggested that bone density (BMD) is a very important risk factor for bone fracture in both males and females. The study was taken into 3 ten thousand 9 thousand out of 12 population studies, with approximately 17 thousand years observed. And analyzing the influence of BMD (bone marrow necrosis factor) on fracture risk in each research population by adopting a Poisson model, and performing combined analysis on each research result by adopting a weighting coefficient. The results show that BMD is a good predictor of fracture, especially hip fracture, for both men and women. For every 1 Standard Deviation (SD) reduction in BMD in the 65 year old group, there was a 2.94-fold increase in the risk of hip fracture in men (2.02-4.27) and a 2.88-fold increase in women (2.31-3.59). However, this effect is age dependent, with a risk gradient significantly higher at 50 years than at 80 years. The risk gradients for various types of fractures and osteoporotic fractures are lower than for hip fractures, and the predictive value of BMD increases with age. In the age group of 65 years, the risk of osteoporotic fractures in men increases 1.41 times (1.33-1.51) and women increases 1.38 times (1.28-1.41) for every 1 SD reduction in BMD. For hip fractures, the time between fracture and measurement of BMD is extended and the predictive value of BMD is diminished, but not significant. The lower the BMD value, the greater the effect predicted for osteoporotic fractures (and various types of fractures), with a 4 SD reduction in the T value of 2.10 (1.63-2.71) and a1 SD reduction in the T value of 1.73 (1.59-1.89). The predicted effect of BMD is also similar for hip fractures. John et al believe that the conclusions drawn from the results of this analysis are of great utility since the clinical study chosen are international. The results of this analysis indicate that BMD can be used for screening for susceptible cases, but in the application process, the effect of age on the predictive value of BMD fracture is taken into account. The method for improving the bone mineral density can select different raw materials when designing the formula of the health food according to different reasons for the lack of the bone mineral density and different action mechanisms. The raw materials frequently used are as follows: 1. calcium agent: if the calcium absorption is normal, 1.00 g to 1.50 g is needed daily. Among the various calcium agents, calcium carbonate is commonly used. For the aged over 65 years old, 0.75 g-2.5 g is taken daily. The large dose of calcium administered to patients who have a lot of side effects and may induce endometrial cancer may have the same effect as the estrogen, and the patients with renal calculus cannot take a large amount of calcium. 2. Vitamin D and its active products: in the past, it was thought that senile osteoporosis patients are often accompanied by vitamin D deficiency, and therefore, it was claimed that vitamin D was given in large amounts, in fact, in addition to those accompanied with osteomalacia (generally, only children are susceptible to osteomalacia, such as rickets), intestinal calcium malabsorption and reduced production of vitamin D metabolites, and vitamin D was given simultaneously in all three cases without supplementation of a large amount of vitamin D. 3. Calcitonin: the calcitonin can reduce bone absorption, reduce calcium in blood circulation, and increase calcium content in bone, and can supplement calcium when used for treating osteoporosis. 4. Phosphate salts: the phosphate for treating osteoporosis is developed in recent years, and the phosphate can promote bone formation, inhibit the damage of bone cells and be used for a long time. N-3 polyunsaturated fatty acids (α -linolenic acid): the n-3 fatty acid influences the bone metabolism of human beings, plays a regulating role on osteoblasts and osteoclasts through different action mechanisms, and the strengthening of the n-3 fatty acid is beneficial to improving the bone density.
The bone joints are formed by connecting adjacent bones by a capsule of connective tissue. The indirect connection between bones is called bone joint. A cavity is arranged between the opposite bone surfaces, and a small amount of synovial fluid is contained in the cavity. Its range of motion is large, and every joint is related to articular surface, articular capsule and articular cavity. Some joints also have ancillary structures such as ligaments, discs, and menisci. The reason why the human body can move freely is that the structure of the bone joints, most of the bone joints are needed for the human body to move, and the cartilage protects the bone from abrasion. With respect to the maintenance of bone joints, hydroxyproline is a vehicle for transporting calcium from plasma to bone cells, and collagen from bone cells is a binder of hydroxyapatite, which together with hydroxyapatite constitutes the main body of bone. Therefore, the intake of calcium in normal body can be ensured as long as enough collagen is taken, and the collagen can be made into health food for supplementing calcium. The osteoarthropathy is based on acute and chronic injuries of articular cartilage or degeneration of articular cartilage, and is clinically seen in the elderly, besides the injuries and degeneration of articular cartilage, the osteoarthropathy has the structural relationship change of the bone joint in the later period. Osteoarthropathy is a chronic joint disease characterized by local articular cartilage degeneration, bone loss, joint edge bony spur formation, joint deformity and subchondral bone densification, and is also known as osteoarthritis, degenerative osteoarthropathy, proliferative arthritis, and senile arthritis. The disease is better for people over 50 years old, women are more than men, and the disease affects the life quality of middle-aged and old patients to different degrees. Almost all cases have varying degrees of pain, progressing slowly with the course of the disease. The joint pain is obvious when the joint starts to move, and is relieved after the joint moves slightly, but the pain is aggravated when the weight bearing and the bone joint move too much, which is the characteristic of the osteoarthropathy. Sometimes the pain may be radioactive, e.g. hip pain may be radiated to the inside of the thigh, near the knee joint. Stiffness of the joints is seen in the early stage, for example, when the knee joints are in a certain position for a long time, voluntary movement is unfavorable, starting is difficult, joint instability gradually occurs later, the bending and stretching range of the joints is reduced, and walking ability is reduced, especially the ability of going up and down steps, squatting, running, jumping and the like is more obviously reduced. Some patients with advanced osteoarthropathy may also have some lower limb deformities, most commonly known as knee varus, commonly known as "legged loop". In the aspect of treating osteoarthropathy, the following points are mainly considered: 1. functional exercise: reasonable exercise can restore muscle contraction force and joint flexibility and prevent and treat osteoporosis, and unreasonable exercise can increase joint load and cause further damage to cartilage, thereby aggravating clinical symptoms. It is often seen that some patients experience symptoms aggravated after an uncomfortable exercise, such as walking, jumping, or even running or climbing, blindly. We advocate that the exercise should be performed with the joint not bearing weight, and recommend the healthy limb bearing weight on the ground, the affected limb bending and stretching the joint, or the sitting position to perform the joint bending and stretching exercise. Do not need to squat as much as possible, which may increase the joint load. The sit-up, the straight leg lifting and the like can be exercised on the bed aiming at the hip joint and the knee joint, and the more times, the better. Swimming is a sport item which is very suitable for knee osteoarthritis patients, does not have great burden on knee joints, and can ensure that muscles can move fully. Breaststroke, however, requires the knee joint to impart torque. Sometimes, poor results are caused, so that free swimming and backstroke are suggested. 2. And (3) improving the prevention consciousness: the patient needs to know the hazard of the disease and the importance of early treatment, improve the understanding of the patient on the risk factors, eliminate and avoid pathogenic factors, be beneficial to controlling the disease and recovering the function, and establish the confidence of overcoming the disease. 3. Joint protection: joint load and movement should be limited, so that the walking stick can be prevented from standing for too long time or walking for a long distance, and the load of the affected joint can be reduced by using the walking stick; the patient with excessive weight should lose weight; attention should be paid to the warm keeping of the affected joint and wind cold resistance; in severe cases, the patient can rest in bed for a short time and brake completely. 4. Local physiotherapy: in the acute stage, the joint is heated, local cold compress is firstly carried out on swelling, and hot compress can be applied after fever abatement and detumescence. In the chronic stage, infrared ray, ultrashort wave, acupuncture, wax therapy, massage, etc. can also be applied.
Cramps in the waist and legs, known as muscle spasm, are a spontaneous and forced contraction of muscles. Leg cramps mainly occur in the muscles of the lower legs and toes, pain is difficult to endure during attack, and especially, people are often waken up during the midnight cramps, pain is difficult to relieve for a long time, and sleep is affected. The reasons for cramping the waist and legs are as follows: cold stimulation. If the user exercises in cold environment in winter, the preparation activity is insufficient; the lower temperature of swimming water in summer can cause leg cramp. When a user sleeps at night, a quilt is not covered, and the muscles of the legs are stimulated by cold and can be cramped to wake up. ② the continuous contraction of the muscle is too fast. When the patient exercises vigorously, the whole body is in a tense state, leg muscles contract too fast, the time for relaxation is too short, local metabolic products lactic acid are increased, and contraction and relaxation of the muscles are difficult to coordinate, so that calf muscle spasm is caused. ③ excessive sweating. The exercise time is long, the exercise amount is large, the sweating is excessive, the salt is not supplemented in time, a large amount of in vivo liquid and electrolyte are lost, metabolic waste is accumulated, the local blood circulation of muscles is not good, and the spasm is easy to occur. Over fatigue. When the person travels for a long distance, climbs a mountain and ascends a height, the muscles of the lower legs are easy to fatigue. Because one foot supports the whole body weight every time of ascending, the muscle of the leg needs six times of the weight of the human body to lift the foot, and when the leg is tired to a certain degree, spasm can occur. Fifthly, calcium deficiency. Calcium ions play an important role during muscle contraction. When the concentration of calcium ions in blood is too low, muscles are easily excited and cramp. Teenagers grow and develop rapidly and are easy to lack calcium, so leg cramps often occur. Sixthly, the sleeping posture is not good. If the user lies on the back for a long time, the quilt is pressed on the foot surface, or lies on the front for a long time, the foot surface is pressed on the bed, certain muscles of the crus are forced to be in an absolute relaxed state for a long time, and the muscles are induced to be passively contractual. The frequent occurrence can be related to vascular diseases.
Those skilled in the art would still expect new methods to increase bone density, enhance bone joint function, and avoid cramping in the waist and legs in the middle aged and elderly. Those skilled in the art still expect new drugs or health products for improving bone density, enhancing bone joint function, and preventing cramping in the waist and legs of the middle aged and the elderly.
Disclosure of Invention
The invention aims to provide a novel method for improving bone density, enhancing bone joint function and avoiding lumbar and leg cramps of middle-aged and elderly people, and the invention also aims to provide a novel medicine or health-care product which is expected to be used for improving bone density, enhancing bone joint function and avoiding lumbar and leg cramps of middle-aged and elderly people. The present invention has been completed based on this finding.
To this end, the present invention provides in a first aspect a composition for increasing bone density and bone joint function in the middle aged and elderly people to avoid cramps in the waist and legs, comprising: kudzu root extract, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate, casein phosphopeptide, and optional physiologically acceptable carrier.
The composition for improving bone density and bone joint function of middle aged and elderly people to avoid cramping in waist and legs according to the first aspect of the present invention comprises: 500 parts of kudzu root extract, 400-500 parts of glucosamine hydrochloride, 300-500 parts of calcium carbonate, 50-150 parts of chondroitin sulfate, 10-40 parts of casein phosphopeptide and optional physiologically acceptable carriers.
The composition for improving bone density and bone joint function of middle aged and elderly people to avoid cramping in waist and legs according to the first aspect of the present invention comprises: 500 parts of kudzu root extract, 420-470 parts of glucosamine hydrochloride, 350-450 parts of calcium carbonate, 75-125 parts of chondroitin sulfate, 20-30 parts of casein phosphopeptide and optional physiologically acceptable carriers.
The composition for improving bone density and bone joint function of middle aged and elderly people to avoid cramping in waist and legs according to the first aspect of the present invention comprises: 500 parts of kudzu root extract, 440 parts of glucosamine hydrochloride, 400 parts of calcium carbonate, 100 parts of chondroitin sulfate, 25 parts of casein phosphopeptide and optional physiologically acceptable carriers.
The composition for improving bone density and bone joint function of middle aged and elderly people to avoid cramping in waist and legs according to the first aspect of the present invention is in the form of a tablet or granule.
The composition for improving bone density and bone joint function of middle aged and elderly people to avoid cramping in waist and legs according to the first aspect of the present invention is in the form of a tablet, and the physiologically acceptable carrier includes xylitol, microcrystalline cellulose, magnesium stearate.
The composition for improving bone density and bone joint function in middle aged and elderly people to avoid cramping in the waist and legs according to the first aspect of the present invention is in the form of a tablet, and the amount of xylitol 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, per 500 parts by weight of the pueraria extract.
The composition for improving bone density and bone joint function in middle aged and elderly people to avoid cramping in waist and legs according to the first aspect of the present invention is in the form of a tablet, and the amount of microcrystalline cellulose is 200 to 300 parts by weight, such as 220 to 280 parts by weight, such as 240 to 260 parts by weight, such as 250 parts by weight, per 500 parts by weight of the pueraria extract.
The composition for improving bone density and bone joint function in middle aged and elderly people to avoid cramping in waist and legs according to the first aspect of the present invention is in the form of a tablet, and the amount of magnesium stearate is 20 to 30 parts by weight, such as 22 to 28 parts by weight, such as 24 to 26 parts by weight, such as 25 parts by weight, per 500 parts by weight of the pueraria extract.
The composition for improving bone density and bone joint function of middle-aged and elderly people to avoid lumbar and leg cramps according to the first aspect of the invention is prepared according to a method comprising the following steps:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate and chondroitin sulfate uniformly;
(2) dissolving casein phosphopeptide in water of 5-8 times, adding xylitol of 2-3 times of the weight of the casein phosphopeptide, uniformly mixing, ventilating the mixture at the temperature of 60-70 ℃ for 2.5-3 hours, and uniformly mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) mixing the dried granules obtained in the above step with magnesium stearate to obtain a composition, and packaging the composition as a granular preparation directly, or further compressing the composition into tablets to obtain a granule or tablet preparation form.
The composition for improving bone density and bone joint function of middle aged and elderly people to avoid cramp in waist and legs according to the first aspect of the present invention is in the form of a tablet formulation. In one embodiment, it is in the form of a tablet of chewable tablets.
It has been surprisingly found that by mixing a solution of casein phosphopeptide with 2-3 times the amount of xylitol followed by aeration treatment at 60-70 ℃ for 2.5-3 hours, a composition produced in this way (compared to when casein phosphopeptide is not treated in this way with xylitol) avoids discoloration of the drug after prolonged standing. The specific experiment is as follows: reference is made to examples 1 to 5, respectively, except that in step (2) the casein phosphopeptide is homogeneously mixed with the corresponding amount of xylitol, and this mixture is used directly in the subsequent steps, obtaining 5 batches of tablets, which can be referred to as supplementation examples 1 to 5, respectively; the tablets of examples 1 to 5 and the tablets of supplementary examples 1 to 5 were left at 40 ℃ for 6 months, the tablets for 0 and 6 months were dissolved in water and filtered to prepare a solution containing casein phosphopeptide 20. mu.g/ml (the color of the solution of examples 1 to 5 was significantly lighter than that of supplementary examples 1 to 5 after 6 months), and the absorbance was measured at 360 nm; the percentage increase in absorbance was calculated for each sample according to the following formula: percent increase in absorbance ═ absorbance at 6 months-absorbance at 0 months ] ÷ absorbance at 0 months × 100%; as a result, the tablets of examples 1 to 5 showed an increase in absorbance of 3.3 to 7.4% and the tablets of supplementary examples 1 to 5 showed an increase in absorbance of 36.7 to 47.2%, the latter being higher than the former, indicating that the latter tablets were more likely to be discolored and darkened.
Further, the second aspect of the present invention provides a method for preparing a composition for increasing bone density and bone joint function of middle aged and elderly people to avoid cramp in waist and legs, the composition comprising: kudzu root extract, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate, casein phosphopeptide, xylitol, microcrystalline cellulose and magnesium stearate, and the method comprises the following steps:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate and chondroitin sulfate uniformly;
(2) dissolving casein phosphopeptide in water of 5-8 times, adding xylitol of 2-3 times of the weight of the casein phosphopeptide, uniformly mixing, ventilating the mixture at the temperature of 60-70 ℃ for 2.5-3 hours, and uniformly mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) mixing the dried granules obtained in the above step with magnesium stearate to obtain a composition, and packaging the composition as a granular preparation directly, or further compressing the composition into tablets to obtain a granule or tablet preparation form.
The method according to the second aspect of the present invention, wherein the composition for improving bone density and bone joint function in middle aged and elderly people to avoid cramping in the waist and legs comprises: 500 parts of kudzu root extract, 400-500 parts of glucosamine hydrochloride, 300-500 parts of calcium carbonate, 50-150 parts of chondroitin sulfate, 10-40 parts of casein phosphopeptide and optional physiologically acceptable carriers.
The method according to the second aspect of the present invention, wherein the composition for improving bone density and bone joint function in middle aged and elderly people to avoid cramping in the waist and legs comprises: 500 parts of kudzu root extract, 420-470 parts of glucosamine hydrochloride, 350-450 parts of calcium carbonate, 75-125 parts of chondroitin sulfate, 20-30 parts of casein phosphopeptide and optional physiologically acceptable carriers.
The method according to the second aspect of the present invention, wherein the composition for improving bone density and bone joint function in middle aged and elderly people to avoid cramping in the waist and legs comprises: 500 parts of kudzu root extract, 440 parts of glucosamine hydrochloride, 400 parts of calcium carbonate, 100 parts of chondroitin sulfate, 25 parts of casein phosphopeptide and optional physiologically acceptable carriers.
The method according to the second aspect of the present invention, wherein the xylitol is present in an amount of 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, per 500 parts by weight of the pueraria lobata extract in the composition for improving bone density and osteoarticular function in middle and old aged people to avoid cramps in the waist and legs.
The method according to the second aspect of the present invention, wherein the amount of the microcrystalline cellulose in the composition for improving bone density and bone joint function in middle aged and elderly people to avoid cramping in waist and legs is 200 to 300 parts by weight, such as 220 to 280 parts by weight, such as 240 to 260 parts by weight, such as 250 parts by weight, per 500 parts by weight of the pueraria extract.
The method according to the second aspect of the present invention, wherein the amount of magnesium stearate is 20 to 30 parts by weight, such as 22 to 28 parts by weight, such as 24 to 26 parts by weight, such as 25 parts by weight, per 500 parts by weight of the pueraria lobata extract in the composition for improving bone density and osteoarticular function of middle aged and elderly people to avoid cramps in the waist and legs.
Further, the third aspect of the invention provides a composition comprising pueraria extract, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate, casein phosphopeptide and an optional physiologically acceptable carrier, and the composition is used for preparing products for improving bone density and bone joint function of middle-aged and elderly people and avoiding cramp in waist and legs.
According to the use of the third aspect of the invention, the composition comprises: 500 parts of kudzu root extract, 400-500 parts of glucosamine hydrochloride, 300-500 parts of calcium carbonate, 50-150 parts of chondroitin sulfate, 10-40 parts of casein phosphopeptide and optional physiologically acceptable carriers.
According to the use of the third aspect of the invention, the composition comprises: 500 parts of kudzu root extract, 420-470 parts of glucosamine hydrochloride, 350-450 parts of calcium carbonate, 75-125 parts of chondroitin sulfate, 20-30 parts of casein phosphopeptide and optional physiologically acceptable carriers.
According to the use of the third aspect of the invention, the composition comprises: 500 parts of kudzu root extract, 440 parts of glucosamine hydrochloride, 400 parts of calcium carbonate, 100 parts of chondroitin sulfate, 25 parts of casein phosphopeptide and optional physiologically acceptable carriers.
According to the use of the third aspect of the invention, the composition is in the form of a tablet or granule.
According to the use of the third aspect of the invention, the composition is in the form of a tablet and the physiologically acceptable carrier comprises xylitol, microcrystalline cellulose, magnesium stearate.
According to the use of the third aspect of the present invention, the composition contains xylitol in an amount of 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, per 500 parts by weight of the pueraria lobata extract.
According to the use of the third aspect of the present invention, the amount of the microcrystalline cellulose is 200 to 300 parts by weight, such as 220 to 280 parts by weight, such as 240 to 260 parts by weight, such as 250 parts by weight, per 500 parts by weight of the puerariae radix extract.
According to the use of the third aspect of the present invention, the composition contains magnesium stearate in an amount of 20 to 30 parts by weight, such as 22 to 28 parts by weight, such as 24 to 26 parts by weight, such as 25 parts by weight, per 500 parts by weight of the pueraria lobata extract.
According to the use of the third aspect of the present invention, the composition is prepared according to a process comprising the steps of:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate and chondroitin sulfate uniformly;
(2) dissolving casein phosphopeptide in water of 5-8 times, adding xylitol of 2-3 times of the weight of the casein phosphopeptide, uniformly mixing, ventilating the mixture at the temperature of 60-70 ℃ for 2.5-3 hours, and uniformly mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) mixing the dried granules obtained in the above step with magnesium stearate to obtain a composition, and packaging the composition as a granular preparation directly, or further compressing the composition into tablets to obtain a granule or tablet preparation form.
In describing the method steps of the present invention, although the particular steps described are distinguished in some detail or language from the steps described in the examples of the detailed description which follow, those skilled in the art can nevertheless fully appreciate the above-described method steps from the detailed disclosure throughout the present application.
Any embodiment of any aspect of the invention may be combined with other embodiments, as long as they do not contradict. Furthermore, in any embodiment of any aspect of the invention, any feature may be applicable to that feature in other embodiments, so long as they do not contradict.
The invention is further described below.
All documents cited herein are incorporated by reference in their entirety and to the extent such documents do not conform to the meaning of the present invention, the present invention shall control. Further, the various terms and phrases used herein have the ordinary meaning as is known to those skilled in the art, and even though such terms and phrases are intended to be described or explained in greater detail herein, reference is made to the term and phrase as being inconsistent with the known meaning and meaning as is accorded to such meaning throughout this disclosure.
Radix Puerariae is dried root of Pueraria lobata (Willd.) Ohwi or Pueraria thomsonii Benth. Collected in autumn and winter, and cut into thick slices or small pieces when the Pueraria lobata is fresh; drying; radix Puerariae is usually called as radix Puerariae, and is prepared by removing outer skin, fumigating with sulfur, slightly drying, cutting into segments or longitudinally cutting into two halves, and drying. Wild kudzu: the rectangular thick sheet or small square is longitudinally cut, the length is 5-35 cm, and the thickness is 0.5-1 cm. The skin was light brown, with longitudinal wrinkles and roughness. The cut surface is yellow-white and the texture is not obvious. Tough and fibrous. No bad smell, slightly sweet taste. And (3) kudzu: the shape of a cylinder, a quasi-spindle shape or a semi-cylinder is 12-15 cm long and 4-8 cm in diameter; some are thick pieces with different sizes, which are longitudinally cut or obliquely cut. The surface is yellowish white or light brown, and the color without peeling is grayish brown. The cross section of the fiber can be seen as light brown concentric ring lines formed by the fiber, and the longitudinal section of the fiber can be seen as a plurality of longitudinal lines formed by the fiber. Body weight, hard texture, rich powder. Kudzuvine root is sweet and pungent in nature and cool in taste. It enters spleen and stomach meridians. Has the effects of relieving muscles and fever, promoting the production of body fluid, promoting eruption, invigorating yang and relieving diarrhea. Can be used for treating fever, headache, stiffness and pain of neck and back, thirst, diabetes, measles without adequate eruption, dysentery, and diarrhea; hypertension neck and neck pain. The kudzu root contains isoflavone components of puerarin, puerarin xyloside, daidzein glycoside, beta-sitosterol and arachic acid, and also contains a large amount of starch (the content of fresh kudzu root is 19-20%). The dried root of kudzu contains 37% starch. The root of the kudzu vine with three-leaf schizophyllum contains 15-20% of starch. Puerarin, daidzein, daidzin, beta-sitosterol, 4', 6 "-diacetylpuerarin and stigmasterol are isolated from the roots of Indian congeneric plants. Pueraria mirifica contains daidzein (daidzein), daidzin (daidzin), puerarin (puerarin), 4 '-methoxy puerarin (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-monoetin), daidzein-8-C-apiosyl (l → 6) -glucoside [ daidzein-8-C-apiosyl (1 → 6) -glucoside ], genistein-8-C-apiosyl (1 → 6) -glucoside [ genistein-8-C-iophyll (1 → 6) -glucoside (1, 6-), puerarin xyloside (PG-2), 3 '-hydroxypuerarin (3' -hydroxypulerin, PG-1), 3 '-methoxyproperin (3' -methoxyproperin, PG-3), 4 '-O-glucosylpuerarin (4' -O-glucosyl puerarin, PG-6), puerarin (puerarol), puerarin (pueroside) A, B, formononetin-7-glucoside (formononetin-7-glucoside), lupenone (lupenone), beta-sitosterol (beta-sitosterol), docosanoic acid (docosanoic acid), tetracosanoic acid (tetracosanoic acid), l-tetracosanoic acid glyceride (glucoerunol-1-monothioside), allantoin (antagon), beta-D-glucoside (beta-D-glucoside), 6, 7-dimethoxy coumarin (6, 7-dimethylycoumarin), 5-methylhydantoin (5-methylhydantoin) and triterpenoid saponins with sophoricediol, cantonensis sarmentriol (cantoniensis), soyasapogenol (soyasapogenol) A, B, kudzu sapogenol (kudzusapogenol) C, A and kudzu sapogenol B methyl ester (kudzusapogenol B methyl ester) as aglycons. Pueraria lobata also contains daidzein, daidzin, puerarin and beta-sitosterol. Radix Puerariae contains daidzin, puerarin, 4 '-methoxy puerarin, daidzein and trace amount of daidzein-4, 7' -diglucoside. The pharmacological action of the kudzuvine root mainly comprises the following aspects: the flavone extracted from the root of kudzu vine can increase the blood flow of brain and coronary blood vessels. After pueraria flavone is injected into internal carotid arteries of anesthetized dogs, cerebral blood flow is increased, vascular resistance is correspondingly reduced, and the effect is maintained for 2-20 minutes, if intravenous injection is performed, the cerebral blood flow is slightly increased, the effect of epinephrine and norepinephrine on contracting cerebral vessels cannot be relieved, but cerebral circulation can be improved for hypertensive arteriosclerosis patients, and the effect is mild. Pueraria flavone and Pueraria wine extract can be injected into dog coronary artery and vein to increase coronary blood flow and reduce vascular resistance. The wine extract of kudzuvine root is injected into abdominal cavity and subcutaneous cavity of rat, the water decoction of kudzuvine root and the crystal extracted from kudzuvine root are injected into abdominal cavity, both the protection effect on the heart ischemia reaction caused by hypophysin and the obvious blood pressure lowering effect on the hypertensive dog are not caused by the oral administration of the water decoction of kudzuvine root. Two components, exciting and suppressing the heart, are reported in decoction of kudzu root (produced in Japan). (II) spasmolysis, wherein the Chinese kudzu root (variety is not shown) and Japanese kudzu root contain flavone of semen phaseoli radiati, and have papaverine-like spasmolysis effect on isolated intestinal canals of mice and guinea pigs, but the Chinese kudzu root has stronger spasmolysis effect than Japanese kudzu root, possibly is related to more contained flavone, and the spasmolysis component can resist histamines and acetylcholine; other isoflavone derivatives separated from Japanese kudzuvine root have no obvious effect of expanding acetylcholine. In addition, substances with contraction action of elbow intestine tube, MTF-101 toxic muscarinic like action, which is proposed in Kudzuvine root produced in Japan, were isolated. And thirdly, the hypoglycemic effect is realized, the kudzuvine root (variety is not shown) decoction is orally taken by the rabbits, the blood sugar rises in 2 hours and then drops, the blood sugar drops at the lowest in 3 and 4 hours, the medicine has no antagonistic effect on the epinephrine hyperglycemia of the rabbits, but increases the epinephrine hyperglycemia, but can promote the early recovery of the blood sugar to be normal. The kudzu root water extract can also lower the blood sugar of the rabbits after the initial rise, has more obvious effect on the blood sugar rise of the starved rabbits, and the ether extract has no obvious influence on the carbohydrate metabolism. Fourthly, the heat-clearing and estrogen-like effects, the Japanese pueraria infusion has obvious heat-clearing effect on the artificial fever rabbits, and the heat-clearing effect lasts for 4 to 5 hours. Radix Puerariae can increase weight of uterus of immature mouse, and has estrogen-like effect. The effective component of the effect is daidzein. The kudzu root extract used in the invention, which can also be called kudzu root total flavone, meets the regulations of the national drug standard YBZ013422006-2009Z, is an extract obtained by extracting kudzu root with water, and is sold in the market at present.
Glucosamine, glucamine, also known as D-Glucosamine, is commonly used as its hydrochloride salt, as well as its sulfate salt. Glucosamine is a compound in which one hydroxyl group of glucose is substituted with one amino group. The molecular formula is C6H13O5N, commonly called aminosugar, and is called aminosugar for short. Also known as glucosamine, widely found in nature, 2-amino-2-deoxy-D-glucose is commonly found in polysaccharides of microbial, animal origin and in conjugated polysaccharides, in the form of N-acetyl derivatives (such as chitin) or N-sulfates and N-acetyl-3-O-lactic acid ethers (muramic acid). Is mainly suitable for knee joint degenerative arthritis, hyperosteogeny and meniscus injury. Glucosamine, a substance synthesized in the human body, is an important nutrient for forming chondrocytes, and is a natural tissue component of healthy articular cartilage. With age, the deficiency of glucosamine in the human body becomes more severe, and articular cartilage is continuously degenerated and worn. A 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: relief of pain, stiffness and swelling due to arthritis: osteoporosis causes cartilage loss, eventually leading to spalling, less cushioning of the cartilage in the joint, and susceptibility to stiffness and inflammation. Glucosamine helps repair damaged cartilage, stimulates the formation of new cartilage, improves inflammation, and relieves joint pain, stiffness and swelling. Strengthening cartilage structure, preventing joint function failure: as the body ages, joint tissues are severely abraded and glucosamine can protect and strengthen cartilage structures and prevent joint function failure due to joint aging. Lubricating joints and maintaining joint function: glucosamine can be prepared into proteoglycan for lubricating joint, preventing friction and pain of bone and joint, and making joint move freely. The treatment functions of glucosamine are mainly as follows: 1. the knee joint degenerative arthritis and the glucosamine treatment of the knee arthritis mainly restore articular cartilage and promote joint synovial fluid to ensure that hard friction does not occur between articular surfaces and symptoms such as pain, swelling, bone friction sound and the like do not occur any more, and the articular gap is restored to be normal and the joint function is completely restored by restoring the articular cartilage. 2. The bone hyperplasia, the exogenously intakes glucosamine, make the glucosamine content in the joint restore the equilibrium state, stimulate cartilage cells to synthesize proteoglycan and collagen fiber, generate cartilage matrix, repair damaged cartilage, improve the self-repair ability of the joint cartilage, repair the joint cartilage and promote joint synovial fluid through the glucosamine, and play a fundamental treatment role in the osteoproliferation arthritis (osteoarthritis). 3. Meniscus injury, glucosamine can repair the damaged meniscus, repair secondary articular surface cartilage damage of meniscus injury simultaneously, fundamentally repair joint injury. Glucosamine can eliminate harmful factors, inhibit and eliminate the synovial inflammatory reaction of joints. 4. Chondromalacia patellae, exogenously supplemented with glucosamine, can repair articular cartilage between patella and femur. 5. Cervical spondylopathy radicular type. 6. Cervical spondylopathy myelotype. 7. Cervical spondylosis and vertebral artery type. 8. Cervical spondylosis sympathetic nerve type, glucosamine through inhibiting intervertebral joint soft tissue inflammatory reaction, eliminate soft tissue edema, and repair damaged cartilage ring, make intervertebral disc protrusion difficult to burst, and promote the normal secretion of joint synovial fluid, make neck activity more flexible. 9. The synovitis, glucosamine, through removing harmful substances in the joint cavity, can also relieve the symptoms of pain, swelling and the like through repairing articular cartilage and pathological synovium. 10. The hand osteoarthritis is supplemented with glucosamine, and the worn joint cartilage can be repaired, so that the joint pain caused by the wear of the joint cartilage is relieved. 11. The foot osteoarthritis is characterized in that after the foot osteoarthritis is taken, the glucosamine can repair the wear of articular cartilage, and if the foot osteoarthritis is taken for a long time, the ankle joint of an athlete who frequently exercises violently can be well protected. The scapulohumeral periarthritis and the glucosamine can repair soft tissues such as tendon, ligament, synovial membrane, bursa synovium and the like by promoting the synthesis of proteoglycan and collagen fiber, promote the generation of joint and bursa synovial fluid, relieve the adhesion of joint soft tissues and recover the activity function of shoulder joints. The lumbar intervertebral disc protrusion can obviously improve the degeneration of intervertebral joint cartilage and intervertebral disc fibrocartilage ring by supplementing glucosamine, and relieve the pain of patients. Rheumatic arthritis and arthritis, wherein the rheumatic arthritis can cause the damage of articular cartilage, supplement glucosamine, repair the abrasion of the articular cartilage and relieve the pain of patients. 15. Supplementing calcium ions required by human body, and improving bone growth and health. Glucosamine is a derivative of a natural amino monosaccharide and is an essential component in cartilage matrix for the synthesis of proteoglycan. Proteoglycan can make the articular cartilage have the function of absorbing impact force by suppressing the tensile force of collagen fibers. In the early stages of degenerative joint diseases, the biosynthesis of aggregated glucosans is increased; in later stages of the disease, the opposite is true. This results in a progressive loss of cartilage elasticity and the development of many symptoms of arthritis. The amino monosaccharide can stimulate chondrocyte to produce glycoprotein with normal polymer structure, inhibit enzymes (such as collagenase) capable of damaging articular cartilage, prevent damage of corticoids and certain nonsteroidal anti-inflammatory drugs to chondrocyte, and reduce release of endotoxin factor of damaged cells. In the development of arthritis, exogenous glucosamine supplementation may play a beneficial role. In vitro experiments, the chondrogenic polymorphous cells synthesize more aggregated glucan if supplemented with glucosamine. Glucosamine also has antioxidant effects in animal models of arthritis, inhibiting the production of superoxide radicals that damage cells. By the above-mentioned route, glucosamine exerts a direct anti-inflammatory effect, can relieve the pain symptoms of osteoarthritis, improve joint function, and can arrest the progression of the course of osteoarthritis. Glucosamine is absorbed 90% orally, rapidly diffuses to blood through biological barriers, distributes to tissues and organs, has affinity to articular cartilage in particular, and can diffuse to articular cartilage matrix to reach cartilage cells. The blood concentration reaches the peak value 4h after the oral administration. 1-8 h after the medicine is taken, the glucosamine concentration can be measured on the liver, the kidney, the stomach wall, the small intestine, the brain, the skeleton, the muscle and the articular cartilage and is increased gradually. The composition decreased in 24 h. t1/2 is 18 h. Glucosamine is metabolized by the liver into smaller molecules that eventually break down into carbon dioxide, water, and urea. 10% of the oral dose is excreted in urine, 11% is excreted in feces and the remainder is mostly excreted in the form of carbon dioxide through the expiratory tract. There are also several studies reporting different results. Barclay states that glucosamine, after oral administration, binds to plasma proteins via the first pass effect with a bioavailability of 26% and the unbound fraction of glucosamine is concentrated at the articular cartilage. In vitro experiments suggest that the blood concentration of glucosamine is higher than 100mmol/L when glucosamine has various effects. Biggee et al administered 1500mg glucosamine to 18 overnight fasted osteoarthritis patients and blood samples were taken at regular intervals. The drug concentration of the blank blood sample is lower than 0.5mmol/L, and the maximum blood drug concentration in the test is 11.5mmol/L, which is far lower than the concentration required for obtaining the in vitro curative effect in other researches. Thus, the efficacy of glucosamine has been questioned by researchers of Biggee et al, since these effects are based on the biological theory of high concentrations in current in vitro studies. Glucosamine is used for treating osteoarthritis of various parts, such as knee joint, hip joint, hand joint, etc. Since the time of introduction of glucosamine into the market, many clinical studies have been conducted at home and abroad. Symptom-improving action: in 1994, Noack et al performed a multicenter, randomized, placebo-controlled study to evaluate the effectiveness and safety of glucosamine. 252 out-patient osteoarthritis patients were randomized according to Riquasisn's index (Lequesne index, from radiation grade I to III, Lequesnez index at least 4 points, and at least 6 months or more) using 500mg glucosamine (treatment group) or placebo (control group) 3 times daily for 4 weeks. The Lequesne index for each group was (10.6. + -. 0.45) points at the start of the study. At the end of the study the treatment group dropped to (7.45 ± 0.5) points (mean reduction of 3.2 points) and the placebo group (8.4 ± 0.4) points (mean reduction of 2.2 points) (P <0.05, S test). The effective rates of the treatment group and the placebo group are 55% (n is 120) and 38% (n is 121), respectively. The tolerance of the patients is good, and no obvious difference is found in 2 groups. The study shows that glucosamine is a safe and effective slow-acting drug for treating osteoarthritis. Structure improvement effect: in 2001, the long-term effect of glucosamine on osteoarthritis was studied by a randomized double-blind placebo-controlled clinical trial, Reginster et al. 212 knee osteoarthritis patients were randomized into groups and were administered 1500mg glucosamine or placebo daily for 3 years. Anterior and posterior radiographs of each knee in full extension loading were taken before and 1 and 3 years after treatment, and the mean width of the tibial and femoral articular compartments was determined using digital image analysis. The minimum articular cavity width is the narrowest part of the articular cavity and is observed by a magnifying glass. Symptom scoring was performed according to WOMAC. The results of the study showed that the mean narrowing of the progressive joint space, as evidenced by X-ray film, was 0.31mm in the placebo group, whereas there was no significant change, only 0.06mm, in the glucosamine group (1500mg/d), with a significant difference between the two groups. Patients taking oral placebo had slightly more severe symptoms than those treated with glucosamine. There was no significant difference between the treatment and placebo groups in the safety and reason for early withdrawal from the trial. It is therefore believed that long-term treatment with glucosamine may prevent the development of knee OA. Glucosamine used in the present invention is commercially available and meets the standard specifications set forth in the national drug administration, national Standard, sixth volume, page 226.
Calcium carbonate is the most common form of calcium supplement for the human body. Calcium ions are indispensable to various physiological activities of the body. It can maintain the biopotential on both sides of cell membrane and maintain normal nerve conduction function. The maintenance of normal muscle tone and relaxation and neuro-muscular conduction, as well as the mechanisms of action of some hormones, are manifested by calcium ions. Calcium ions are the form of elemental calcium present in the compound. The calcium ion is formed by losing two electrons from the calcium atom. Calcium (Ca) is one of the important constituents of the human body and generally exists in the form of calcium ions. Calcium is present in large amounts in the human body, mostly in bones and teeth, and in small amounts in blood and tissues. Since metabolism requires a certain amount of calcium to be supplemented from food every day. Adults recommend a daily intake of 1000 mg and for long bodies 1300 mg. Thus, teenagers require a higher amount of calcium than adults because of the need for skeletal development. The height development is related to heredity, but also related to acquired nutrition. It is important to ensure that adequate nutrition includes calcium, which is why people today are on average taller than parents. Calcium ions are present in various foods, the most abundant in milk and dairy products. For example, about 200 ml milk (about one cup) contains about 300 mg of calcium ions. So that adding two cups of milk is sufficient even if the appetite is bad. If the food needs to be supplemented, the food with high calcium content such as bean products, spinach and the like is eaten, and the natural food with balanced nutrition is the best choice. Calcium ions are indispensable to various physiological activities of the body. It can maintain the biopotential on both sides of cell membrane and maintain normal nerve conduction function. The maintenance of normal muscle tone and relaxation and neuro-muscular conduction, as well as the mechanisms of action of some hormones, are manifested by calcium ions. Its main physiological functions are all based on the above basic cell functions, and mainly have the following points: 1. calcium ions are coagulation factors and participate in the coagulation process; 2. participating in the contraction process of muscles (including skeletal muscles and smooth muscles); 3. participate in synthesis and release of neurotransmitters, synthesis and secretion of hormones; 4. is an important substance for bone formation. The mechanism of several important actions is as follows: conduction of neural signals, mechanism: promoting neurotransmitter secretion. When the first cell is excited, an electric impulse is generated, and then calcium ions outside the cell flow into the cell, so that the cell secretes a neurotransmitter, and the neurotransmitter is combined with a protein molecule on the adjacent next-stage nerve cell membrane, so that the next-stage nerve cell generates a new electric impulse. By analogy, the nerve signals are transmitted one by one, so that a complex signal system is formed, and even the advanced functions of the brain such as learning, memory and the like finally appear. When the body is in a calcium deficiency state, the release of neurotransmitters is blocked, and the excitation mechanism and the inhibition mechanism of the human body are destroyed. In the case of children with calcium deficiency, night cry, night convulsion, dysphoria and insomnia can seriously cause brain dysgenesis, and symptoms such as sluggish response, hyperactivity, difficulty in learning and the like can be caused, thus affecting brain maturity and intelligence. Let the heart beat, the mechanism: the positively charged calcium ions generate potential difference inside and outside the cell. The positively charged calcium ions pass through the cell membrane and enter the myocardial cells, and a large potential difference is formed due to large difference of calcium concentration inside and outside the cells, so that the physiological effect of stimulating cell membrane contraction is generated. The myocardial cells contract and pump calcium ions out of the cell membranes to form reverse potential difference, and the myocardial cell membranes begin to relax under the action of the reverse potential difference; after relaxation, the permeability of the cell membrane is increased, calcium ions pass through the cell membrane again to enter myocardial cells, and the myocardial contraction is caused again, so that the heart beats up with rhythm.
The mechanism of transmitting the defense signal is as follows: the foreign antigen activates T cell receptor, initiates a calcium ion-mediated signaling pathway, and promotes the differentiation and growth of immune cells. When external invaders such as germs, bacteria, poisons and the like invade the human body, calcium ions firstly send out early warning signals; the calcium ions then signal the nature of the invader, and the immune system then organizes the corresponding immune cells to capture and phagocytose the enemy. Once calcium deficiency occurs, the immune system is degraded and disordered, causing diseases. Such as: autoimmune diseases such as lupus erythematosus and rheumatism; skin diseases: dermatitis, acne, etc. Calcium supplement has important effect on treating the diseases and adverse symptoms of calcium function. The mechanism for modulating the activity of enzymes is: intracellular calmodulin binds with calcium ions to form a complex, which activates the activities of various enzymes in the body. If the skin is cut and bleeding occurs, calcium ions immediately send out signals to activate thrombin step by step and start a blood coagulation mechanism to stop bleeding. The nutrition in food can be absorbed by human body only by the decomposition of enzyme, and the activity of various enzymes and hormones such as protease, lipase, amylase, ATP enzyme and the like can be filled up only by the action of calcium ions, so the nutrition has the theory of 'calcium supplement, which is the root of supplementing all nutrition'. Regulates the maturation and fertilization of germ cells by the following mechanisms: the foremost end of sperm DNA is a acrosome composed of calcium. The foremost end of the sperm-borne DNA is a calcium acrosome, which causes the sperm to break and penetrate the inner membrane of the egg cell upon reaching the egg cell edge, and fertilization occurs as a moment. While the waves, which consist of calcium, surround the egg cells, this is called calcium oscillation. Calcium oscillations act to activate the ovum, allowing it to acquire fertility, from which life-long inoculation begins. Therefore, insufficient calcium directly affects human sexual function and sperm motility, resulting in infertility.
Recent studies have found that calcium is involved in a wide range of physiological processes such as control of cellular excitability, cellular metabolism, maintenance of cellular morphology, regulation of the cell cycle, and the like. Calcium ions can activate signal transduction related enzymes, which are mainly expressed in the following aspects: 1. the distribution of calcium ions in cells has distinct regional characteristics, the concentration of calcium in extracellular fluid free is much higher than that in cells, and more than 90% of calcium ions in cells are stored in intracellular calcium stores (in endoplasmic reticulum and mitochondria), and the concentration of calcium in cytoplasm is very low. If the calcium channel of the cytoplasmic membrane or intracellular calcium pool is opened, it can cause the influx of extracellular calcium or the release of calcium from the intracellular calcium pool, resulting in a sharp increase in the cytosolic calcium ion concentration. After entering cytoplasm, the calcium ion can return to extracellular or intracellular calcium reservoir through calcium pump (calcium ion-ATP enzyme) on cytoplasmic membrane and calcium reservoir membrane to maintain low calcium state in cytoplasm. 2. The downstream signaling molecule for calcium ions is calmodulin (calponin), a calcium binding protein (CaM), which has 4 domains, each of which binds 1 calcium ion. Calmodulin is not easily bound to calcium ions when the concentration of calcium ions in cytoplasm is low; as the cytosolic calcium ion concentration increases, calmodulin binds to different numbers of calcium ions, forming calcium ion/calmodulin complexes of different conformations. Calmodulin itself is inactive, and has a regulatory function after forming a calcium ion/calmodulin complex, and can regulate the activity of calmodulin-dependent protein kinase. 3. Calmodulin is not the only target molecule for calcium ions, which, in addition to calmodulin, bind a variety of signal transduction molecules, PKC, AC, and cAMP-PDE, which are activated by allosteric effects.
CHONDROITIN SULFATE (CS), a class of glycosaminoglycans that is covalently linked to proteins to form proteoglycans. Chondroitin sulfate is widely distributed on the extracellular matrix and cell surface of animal tissues, and sugar chains consisting of alternating glucuronate and N-acetylgalactosamine (also called N-acetylgalactosamine) disaccharide units are linked to serine residues of core protein by a sugar chain-like domain. Chondroitin sulfate is present in all organisms from nematodes to humans, except plants, and performs a number of important physiological functions. Although the backbone structure of the polysaccharide is not complex, it exhibits a high degree of heterogeneity in terms of degree of sulfation, sulfate groups and distribution of the two differences into the isomeric uronic acid re-chains. The fine structure of chondroitin sulfate determines the specificity of function and the interaction with various protein molecules. In 1956, Meyer et al first started to study the type and amount of acid mucopolysaccharides in different tissues, and identified the presence of CS and mucopolysaccharides such as hyaluronic acid, keratan sulfate, etc. in connective tissues. The unsaturated sugars, including the oligosaccharides or disaccharides of low molecular CS and CS, produced by CS under acidic, alkaline and enzymatic conditions are all involved in the β -elimination reaction. The degradation degree of CS under acidic, basic and neutral conditions is represented by the ultraviolet absorbance value at 232nm, and the larger the ultraviolet absorbance value is, the larger the degradation degree is, thereby reflecting the stability of CS under different conditions. CS is an acidic mucopolysaccharide substance extracted from animal tissue, and is white or quasi-white powder; no odor; it has hygroscopicity. The water solution of the product is viscous and will not coagulate when heated. The product is soluble in water, insoluble in organic solvents such as ethanol, acetone, and diethyl ether, and its salts are stable to heat and can not be damaged even when heated to 80 deg.C. The chondroitin sulfate aqueous solution is unstable when meeting higher temperature or acid, and is mainly deacetylated or degraded into monosaccharide or polysaccharide with smaller molecular weight. Chondroitin sulfate is widely used as a medicine for treating joint diseases in the main medical application way, is used together with glucosamine, has the effects of relieving pain and promoting cartilage regeneration, and can fundamentally improve joint problems. Randomized placebo-controlled clinical trials have demonstrated that chondroitin sulfate can reduce pain in osteoarthritis patients, improve joint function, reduce joint swelling and fluid accumulation to prevent gap narrowing in the knee and hand joint areas. Provides a cushion effect, relieves the impact and friction during movement, can absorb water into proteoglycan molecules, thickens cartilage, and increases the amount of synovial fluid in joints. One of the important functions of chondroitin is to act as a transport conduit, transporting important oxygen supplies and nutrients to the joint, helping to remove waste from the joint, and removing carbon dioxide and waste. Since articular cartilage is not supplied with blood, all oxygenation, nourishment and lubrication comes from the synovial fluid. Chondroitin sulfate has protective effect on corneal collagen fiber, can promote growth of fiber in matrix, enhance permeability, improve blood circulation, accelerate metabolism, and promote absorption of penetrating fluid and elimination of inflammation; the polyanion has strong water retention, can improve the water metabolism of corneal tissues of eyes, has strong affinity to the cornea, can form a layer of breathable water retention film on the surface of the cornea and improves the dry symptom of the eyes. By promoting the generation of stroma, a framework is provided for the migration of cells, and the migration of corneal epithelial cells is facilitated, so that the healing of corneal wound, the absorption of exudate and the elimination of inflammation are promoted. Can be used for treating nervous headache, trigeminal neuralgia, coronary heart disease, angina pectoris, myocardial anoxia, cardiovascular and cerebrovascular diseases, arthralgia, atherosclerosis, hepatitis, etc., wherein CS has anticoagulant and antithrombotic effects, and can also be used for adjuvant treatment of auditory disorder and liver function injury caused by streptomycin and adjuvant treatment of hyperlipemia. Can be used as additive in health product and food, and has effects in improving body constitution, resisting bacteria, caring skin, and resisting aging. Improve hearing and dry skin. Can inhibit the absorption of lipid and glucose in small intestine in vivo to achieve weight reducing effect.
Chondroitin sulfate is widely found in human and animal cartilage tissues. The medicinal preparation mainly contains two isomers of chondroitin sulfate A and chondroitin sulfate C, and the contents of chondroitin sulfate in the cartilages of different varieties and ages of animals are different. The pharmacological action is shown as follows: 1. CS can remove lipid and lipoprotein in blood, remove cholesterol in peripheral blood vessel of heart, prevent and treat atherosclerosis, and increase intracellular conversion rate of lipid and fatty acid. 2. CS can effectively prevent and treat coronary heart disease. The compound has the effects of resisting atherosclerosis and atherogenic plaque formation on an experimental arteriosclerosis model; increase the coronary artery branch or collateral circulation of atherosclerosis, and accelerate the healing, regeneration and repair of myocardial necrosis or degeneration caused by experimental coronary arteriosclerosis or embolism. 3. Can increase the biosynthesis of messenger ribonucleic acid (mRNA) and deoxyribonucleic acid (DNA) of cells and promote the metabolism of cells. 4. Has low anticoagulant activity. Chondroitin sulfate has a mild anticoagulant effect, and per 1mg chondroitin sulfate A is equivalent to the anticoagulant activity of 0.45U heparin. This anticoagulant activity does not depend on antithrombin III, and it can exert anticoagulant activity through the fibrinogen system. 5. Chondroitin sulfate also has antiinflammatory, wound healing promoting and antitumor effects. The long-term clinical application of chondroitin sulfate shows that lipid such as fat deposited on the wall of artery and vein can be effectively removed or reduced, and the plasma cholesterol can be obviously reduced, so that the formation of atherosclerosis can be prevented. Chondroitin sulfate is used for treating neuralgia, nervous migraine, arthralgia, arthritis, scapular arthralgia, abdominal postoperative pain, etc. Preventing and treating auditory disorder caused by streptomycin, and auditory dysesthesia, tinnitus, etc. caused by various noises, with remarkable effect. It can be used for the adjuvant treatment of chronic nephritis, chronic hepatitis, keratitis and corneal ulcer. The cartilage in shark cartilage has antitumor effect. In addition, chondroitin sulfate is also used in cosmetics, wound healing agents, and the like. Chondroitin sulfate is an acidic mucopolysaccharide, is one of important components in eye tissues, has the effects of promoting corneal water metabolism and improving cornea, and is suitable for asthenopia and xerophthalmia. The chondroitin sulfate can effectively improve the bone quality, the self-regulation mechanism of an organism is inhibited by increasing the supply of the chondroitin sulfate, the bone hardening is reduced, the compact and flexible bone is more fragile than the fragile bone, the volume is reduced by 10 percent, and the strength is greatly enhanced. Especially the facial contour, is not easy to deform or expand, and the tissue adhesion is improved. The outline skeleton process is reduced, and the young state is restored. It is important to take chondroitin together with glucosamine because chondroitin promotes the process of glucosamine penetration into joints. Several studies, including one of the CINEFL research institutions published in the new england journal of medicine, have shown that the combined ingestion of glucosamine and chondroitin is more effective in protecting, reversing damage and promoting repair of articular cartilage and membranous bone, resulting in a reduction in bone sclerosis and rendering the bone young. It is important to take chondroitin together with glucosamine because chondroitin promotes the process of glucosamine penetration into joints. Chondroitin sulfate also inhibits enzymes that break down cartilage (e.g., collagenase, elastase, and cathepsin) to prevent cartilage from being broken down or dissolved, or from hardening. Can start from the root of the problem and inhibit the activity of COX-2 so as to stop joint inflammation.
Casein Phosphopeptides (CPP for short) are polypeptides with biological activity prepared by using cow milk Casein as a raw material and adopting a biological technology. The CPP molecule consists of twenty to thirty-few amino acid residues, including 4-7 phosphoserine groups in clusters. A large number of tests prove that the CPP can effectively promote the absorption and utilization of divalent mineral nutrients such as calcium, iron, zinc and the like by a human body. The casein phosphopeptide can be used in various nutritional and health foods, and can effectively promote absorption and utilization of divalent mineral nutrients such as calcium, iron, zinc and the like by human bodies. The casein phosphopeptide is prepared by refining and purifying casein hydrolyzed by pancreatin or trypsin, and has a core structure as follows: -Ser (P) -Glu-Glu- (Ser: serine, Glu: glutamic acid, P: phosphate). Phosphoserine residues (-Ser (P)) in the structure exist in clusters, are negatively charged in the pH alkalescent environment of the intestinal tract, can prevent further action of digestive enzymes, and enable the CPP not to be further hydrolyzed and stably exist in the intestine. Domestic researches find that the smaller the molar ratio of nitrogen to phosphorus in the CPP, the shorter the peptide chain of the CPP, and the higher the density of phosphate group, the higher the purity of the CPP, and the stronger the effect of promoting the absorption and utilization of calcium. Calcium is easily absorbed only when existing in an ionic form, and is easily lost when forming insoluble salt with acid radical ions in neutral and weak alkaline environments. The absorption effect of CPP on calcium is mainly shown in that the CPP can be combined with calcium in neutral and alkalescent environments, the generation of insoluble precipitates is inhibited, the loss of calcium is avoided, and finally the calcium is passively absorbed due to the increase of the concentration of free calcium. The current research shows that the action of CPP in promoting calcium absorption is mainly shown in the following aspects: the absorption of calcium by the small intestine is promoted, and grains in human diet contain a large amount of high-phosphorus components such as phytic acid, phytic acid and the like, and are combined with calcium in the environment of pH 7-8 at the lower end of the small intestine to generate calcium phosphate precipitate. The CPP can inhibit the formation of calcium phosphate precipitate, keep the concentration of free calcium higher, promote the passive absorption of calcium, and become another way for vitamin D to be used as a calcium absorption enhancer. Animal experiments show that the CPP can promote the absorption and utilization of calcium, weaken the action of osteoclast and inhibit the resorption of bone. It is thought that post-prandial chewing of cheese stimulates saliva secretion, which buffers the erosion of enamel by acidic substances on plaque, and helps prevent dental caries. In recent years, researches show that the CPP contained in the cheese can combine calcium ions in food at decayed tooth positions to reduce demineralization of enamel so as to achieve the aim of resisting decayed tooth. Researches show that the sperm in the culture solution containing the CPP obviously has higher capability of penetrating through the egg cells, and can also reduce the variation degree of the sperm so as to ensure that the embryo development is more stable. CPP also improves the bioavailability of metal ions such as iron, zinc, magnesium and the like, so that the CPP is called a peptide substance with the function of a metal carrier. At present, CPP is applied to food and health care products such as curry rice, beverage, chewing gum and the like for children abroad. Research and application on the treatment of calcium deficiency of children, osteoporosis and infertility of the elderly and tooth health are also in progress. Because CPP is polypeptide extracted from natural protein, it has advantages of small adverse reaction, safety and reliability, and thus will be widely used. The sensitization reaction of casein, skim milk protein and CPP is studied abroad, and the sensitization of CPP is found to be very small, which shows that the CPP can be applicable to the constitution allergic to milk. However, it should also be noted that the factors influencing the action of CPP are very complex and the role in calcium metabolism must be studied intensively. In the environment that the pH value of casein phosphopeptide is neutral to alkalescent in human intestinal tract, the CPP can chelate calcium, iron and zinc ions and protect the calcium, iron and zinc ions from being precipitated by anions of phosphoric acid, oxalic acid, phytic acid and the like in diet, so that the absorption and utilization of calcium, iron, zinc and the like are effectively promoted. The CPP is a novel product developed with a view to improving the absorption and utilization of calcium, and compared with the conventional calcium absorbent vitamin D, the CPP has the following characteristics: the CPP can promote the absorption of divalent mineral nutrients such as iron, zinc and the like besides the function of promoting calcium absorption. Iron and zinc are mineral substances which are most easily lacked by Chinese people except calcium, and if the calcium is simply and excessively supplemented, the absorption of the iron and the zinc is influenced to a certain extent. If the CPP is added into a calcium, iron and zinc enriched nutritional food or a nutritional health-care product, the absorption of calcium can be improved, and the absorption utilization rate of iron and zinc can be improved, so that the potential adverse effect of a common calcium supplement on the absorption of iron and zinc is effectively overcome, which is a characteristic that any other calcium supplement does not have. 2. Vitamin D promotes the active transport and absorption of saturable calcium in the upper small intestine, and the action of vitamin D is influenced by age and calcium intake; CPP is an unsaturated passive diffusion absorption of the lower small intestine which is not affected by age and changes in calcium intake, whereas calcium is absorbed by passive diffusion much more than by active transport. The CPP product also has good stability, and the shelf life can reach more than 18 months under the dry and dark conditions. After the additive is added into a product, the stability is good in the range from acidity to neutrality, and the additive can resist high temperature treatment of 120 ℃ for 30 minutes. Under the alkaline condition, the stability is poor, the dephosphorylation reaction is aggravated along with the increase of the heating temperature and the extension of the heating time, and the function of the CPP is influenced. Under normal use conditions, both the structure and function of a CPP are stable. 3. Dietary enrichment of VD increases calcium absorption, but excessive VD intake can cause kidney and bone damage. If a certain amount of CPP is added while calcium is enriched in the diet, the calcium in the intestinal tract can be kept in a dissolved state, so that the absorption and utilization of the calcium are effectively promoted, and the CPP is derived from milk protein and can not generate any toxic or side effect on a human body even if the CPP is taken in an excessive amount. In addition, the CPP has the characteristic of complete dissolution in a wide pH range, can resist high-temperature treatment, has good stability, has the characteristics of low amount and high efficiency when being added into food, and the product added with the CPP can keep the original flavor and taste. The calcium-holding capacity of a CPP, i.e., the amount of calcium that is held in solution by the CPP under certain conditions. In a solution system with calcium ions and phosphate radicals, when the pH is alkaline, a calcium phosphate precipitate is formed. The presence of CPP reduces the loss of calcium due to calcium phosphate precipitation, keeping more calcium in solution. Ca: p is 1: 1(8 mM: 8Mm) and 2: 1(12 Mm: 6Mm), 200ppm of CPP was added to the system, and the mixture was incubated at 35 ℃ for 1 hour. Ca: p is 1: 1 and 2: at 1, the CPP has calcium holdup (expressed in moles of calcium that can remain dissolved per mole of organophosphorus in the CPP molecule) of 37.2 and 28.0, respectively. In the prevention of osteoporosis, the animal model used in the animal test is an ovariectomized female old rat. CPP was added to the feed to prepare a test group, and the series 2 was a control group to which no CPP was added to the feed. The relative bone density of the test group was significantly higher than the control group by the time the test was carried out for 4 months, indicating that CPP had a good effect in preventing bone loss in aged female rats. CPP has moderate binding with calcium, and the binding strength is that calcium ions can be protected from being precipitated and large amounts of dissolved calcium can be promoted to be transported to intestinal mucosa without influencing the absorption of calcium due to too tight binding. The binding of CPP and calcium is dynamic, and calcium ions are continuously bound, released, recombined and released by CPP, so that more than 30 calcium ions can be protected from precipitation by one phosphate group in CPP molecules.
Scientific studies have shown that under normal conditions the absorption rates of various calcium sources vary a little. Milk is a well-known and most-favored calcium-supplementing food for human, and the reason is that besides being rich in calcium, milk zymoprotein can generate part of CPP in vivo through the action of intestinal protease, and the CPP can promote the absorption and utilization of calcium, in other words, the absorption rate cannot be the basis for selecting a calcium source by manufacturers, and the addition of a proper amount of calcium absorption promoter CPP in the product is the way of improving intelligence. The CPP is a product extracted from casein in milk by a biotechnology and is genuine 'natural milk essence', so that the CPP is most suitable to be added into a calcium supplement product.
CPP has the property of being completely dissolved in a wide pH range, is resistant to high temperature treatment, and has good stability, and thus, can be added to various products as follows: when the CPP is applied to products containing gas (can make foams fine and durable and promote the absorption of mineral substances in the foams), the CPP can achieve the aim of more perfecting and reasonability of the product formula, truly achieving the aim of supplementing the mineral nutrients to human bodies, and simultaneously realizing the upgrading and updating of original products. In addition, the original flavor and mouthfeel of the product added with the CPP can be kept unchanged. The CPP is added into the calcium and iron reinforced products, so that the products have the characteristics different from other similar products in the market and are in the leading position in the market. The CPP can not only promote the absorption of calcium, but also has good promotion effect on the absorption and utilization of iron and zinc. Therefore, the development of the CPP-added nutritional food and health care product can really achieve the aim of effectively supplementing mineral substances lacking in human bodies, meet the nutritional requirements of people and certainly generate great economic and social benefits. The casein phosphopeptide is derived from natural high-quality protein, namely cow milk casein, can effectively improve the intake, absorption and utilization rate of divalent mineral substances such as calcium, iron, zinc and the like of a human body, and also has the effects of strengthening teeth, strengthening teeth and repairing gum and teeth. CPP is a novel nutritional product developed by aiming at improving the absorption and utilization rate of calcium, is one of bioactive peptide type food additives which are industrially produced so far, has high absorption rate compared with VD, has no toxic or side effect, and can improve the absorption rate of other divalent mineral substances such as zinc, iron and the like. CPP promotes passive diffusional absorption of unsaturated calcium in the lower small intestine, which is independent of age and VD.
In the composition of the present invention, it has been unexpectedly found that the addition of a small amount of glyceryl behenate together with chondroitin sulfate can significantly improve the stability of puerarin, an important active ingredient therein, and it has been found through experiments that the stability of puerarin is affected by chondroitin sulfate. The specific method and result for improving the stability of puerarin are as follows: with reference to examples 1 to 5, respectively, except that in step (1), glyceryl behenate was added together with chondroitin sulfate (in each case, the amounts added were 20%, 25%, 15%, 18%, and 22% by weight of chondroitin sulfate), 5 tablets referred to as supplement examples a1 to a5, respectively; the tablets of examples 1 to 5 and the tablets of supplementary examples a1 to a5 were allowed to stand at 40 ℃ for 6 months, and the puerarin content in each tablet was measured at 0 month and 6 months by the [ content measurement ] method for pueraria lobata carried on page 333 of the first part of the "chinese pharmacopoeia", 2015 edition; the residual percentage of puerarin for each sample was calculated as follows: puerarin content of 6 months ÷ puerarin content of 0 month x 100%; as a result, the residual percentage of puerarin in the tablets of examples 1 to 5 is 90.6 to 92.2 percent, the residual percentage of puerarin in the tablets of supplement examples a1 to a5 is 98.8 to 99.6 percent, and the residual percentage of puerarin in the tablets of supplement examples a1 to a5 is higher than that in the former, which shows that the puerarin which is an important physiologically active substance in the tablets of the latter is obviously more stable; further, referring to examples 1 to 5, respectively, except that chondroitin sulfate was not added to the formulation, 5 batches of tablets, which may be referred to as supplementation examples b1 to b5, respectively, were obtained, and the five batches were treated for 40 to 6 months in the same manner as above, and the remaining percentage of puerarin at 6 months was measured and calculated, and as a result, their remaining percentage of puerarin was 98.1 to 99.3%. This indicates that the significant decrease in puerarin content in examples 1-5 is adversely affected by chondroitin sulfate, and this adverse effect can be overcome by adding glyceryl behenate, which is a conventional pharmaceutical adjuvant in the art. Thus, according to any aspect of the invention, glyceryl behenate is also added thereto. In one embodiment, the glyceryl behenate is added in an amount corresponding to 15% to 25% by weight of the chondroitin sulfate. In one embodiment, glyceryl behenate is added with chondroitin sulfate.
The traditional Chinese medicine composition for improving bone density, improving bone joint function and avoiding or reducing cramp of waist and legs for middle-aged and elderly people is prepared from kudzu root extract, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate and casein phosphopeptide. The composition has the combined biological efficacy of the medicinal materials, and particularly has the efficacies of obviously improving the bone mineral density, improving the function of bone joints and avoiding or reducing cramps in waist and legs. For example, for 36 subjects with low bone density, 10g of the composition obtained in example 1 of the present invention is administered to each subject every day, and the composition is taken twice a day in the morning and at night, and after 2 months, the bone density of all subjects is increased by 23% or more to a range of 23.3% to 27.6%. This indicates that the combination of the present invention has excellent effect of increasing bone density, and these subjects have a significant improvement in feedback bone joint function after 2 months. For another example, for 48 subjects who experienced leg cramps 3 times or more in approximately 1 month, 10g of the composition obtained in example 1 of the present invention was administered to each subject every day, and the administration was continued twice a day in the morning and evening for 2 weeks, and all subjects did not experience leg cramps for 2 months after 2 weeks.
In addition, based on the physiological properties of various medicinal materials in the traditional Chinese medicine composition for improving bone density, improving bone joint function and avoiding or reducing lumbar and leg cramps for middle-aged and elderly people, the traditional Chinese medicine composition for improving bone density, improving bone joint function and avoiding or reducing lumbar and leg cramps for middle-aged and elderly people can be expected to show biological effects generated by the medicinal materials respectively or in combination. For example, the traditional Chinese medicine composition for improving bone density, improving bone joint function and avoiding or reducing cramps in waist and lower extremities of middle-aged and elderly people can be endowed with the respective typical biological effects of kudzu root, glucosamine hydrochloride, calcium carbonate, chondroitin sulfate and casein phosphopeptide as described above. Thus, the use of the third aspect of the present invention also includes the uses relating to these therapeutic/prophylactic effects described above.
Detailed Description
The present invention will be further described by the following examples, however, the scope of the present invention is not limited to the following examples. It will be understood by those skilled in the art that various changes and modifications may be made to the invention without departing from the spirit and scope of the invention. The present invention has been described generally and/or specifically with respect to materials used in testing and testing methods. Although many materials and methods of operation are known in the art for the purpose of carrying out the invention, the invention is nevertheless described herein in as detail as possible.
The total charge per batch in the following composition was 10 kg.
Example 1: preparation of a Chinese medicinal composition
The formula is as follows: 500 parts of kudzu root extract, 440 parts of glucosamine hydrochloride, 400 parts of calcium carbonate, 100 parts of chondroitin sulfate, 25 parts of casein phosphopeptide, 760 parts of xylitol, 250 parts of microcrystalline cellulose and 25 parts of magnesium stearate.
The preparation method comprises the following steps:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate and chondroitin sulfate uniformly;
(2) dissolving casein phosphopeptide in 6 times of water, adding xylitol 2.5 times of casein phosphopeptide, mixing, ventilating the mixture at 65 deg.C for 2.75 hr, and mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) the dried granules obtained in the above step were mixed with magnesium stearate uniformly to obtain a composition, which was further compressed into tablets, each 2.5 g, as chewable tablets.
Example 2: preparation of a Chinese medicinal composition
The formula is as follows: 500 parts of kudzu root extract, 400 parts of glucosamine hydrochloride, 500 parts of calcium carbonate, 50 parts of chondroitin sulfate, 40 parts of casein phosphopeptide, 600 parts of xylitol, 280 parts of microcrystalline cellulose and 22 parts of magnesium stearate.
The preparation method comprises the following steps:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate and chondroitin sulfate uniformly;
(2) dissolving casein phosphopeptide in 7 times of water, adding xylitol 2 times of casein phosphopeptide, mixing, ventilating the mixture at 65 deg.C for 2.75 hr, and mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) the dried granules obtained in the above step were mixed with magnesium stearate uniformly to obtain a composition, which was further compressed into tablets, each 2.5 g, as chewable tablets.
Example 3: preparation of a Chinese medicinal composition
The formula is as follows: 500 parts of kudzu root extract, 500 parts of glucosamine hydrochloride, 300 parts of calcium carbonate, 150 parts of chondroitin sulfate, 10 parts of casein phosphopeptide, 900 parts of xylitol, 220 parts of microcrystalline cellulose and 28 parts of magnesium stearate.
The preparation method comprises the following steps:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate and chondroitin sulfate uniformly;
(2) dissolving casein phosphopeptide in 8 times of water, adding xylitol 3 times of casein phosphopeptide, mixing, ventilating the mixture at 60 deg.C for 3 hr, and mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) the dried granules obtained in the above step were mixed with magnesium stearate uniformly to obtain a composition, which was further compressed into tablets, each 2.5 g, as chewable tablets.
Example 4: preparation of a Chinese medicinal composition
The formula is as follows: 500 parts of kudzu root extract, 470 parts of glucosamine hydrochloride, 350 parts of calcium carbonate, 125 parts of chondroitin sulfate, 20 parts of casein phosphopeptide, 800 parts of xylitol, 240 parts of microcrystalline cellulose and 26 parts of magnesium stearate.
The preparation method comprises the following steps:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate and chondroitin sulfate uniformly;
(2) dissolving casein phosphopeptide in 5 times of water, adding xylitol 2.5 times of casein phosphopeptide, mixing, ventilating the mixture at 70 deg.C for 2.5 hr, and mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) the dried granules obtained in the above step were mixed with magnesium stearate uniformly to obtain a composition, which was further compressed into tablets, each 2.5 g, as chewable tablets.
Example 5: preparation of a Chinese medicinal composition
The formula is as follows: 500 parts of kudzu root extract, 420 parts of glucosamine hydrochloride, 450 parts of calcium carbonate, 75 parts of chondroitin sulfate, 30 parts of casein phosphopeptide, 700 parts of xylitol, 260 parts of microcrystalline cellulose and 24 parts of magnesium stearate.
The preparation method comprises the following steps:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate and chondroitin sulfate uniformly;
(2) dissolving casein phosphopeptide in 6 times of water, adding xylitol 2.3 times of casein phosphopeptide, mixing, ventilating the mixture at 65 deg.C for 2.5 hr, and mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) the dried granules obtained in the above step were mixed with magnesium stearate uniformly to obtain a composition, which was further compressed into tablets, each 2.5 g, as chewable tablets.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Claims (14)

1. A composition in the form of a tablet for increasing bone density and bone joint function in the middle aged and elderly people to avoid cramping in the waist and legs is prepared from the following components: 500 parts of kudzu root extract, 400-500 parts of glucosamine hydrochloride, 300-500 parts of calcium carbonate, 50-150 parts of chondroitin sulfate, 10-40 parts of casein phosphopeptide and a physiologically acceptable carrier;
the physiologically acceptable carrier comprises xylitol, microcrystalline cellulose, magnesium stearate, glyceryl behenate;
the content of xylitol is 500-1000 parts by weight, the content of microcrystalline cellulose is 200-300 parts by weight, the content of magnesium stearate is 20-30 parts by weight, and the addition amount of glyceryl behenate is 15-25% of the weight of chondroitin sulfate;
the composition is prepared according to a method comprising the following steps:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate, chondroitin sulfate and glyceryl behenate uniformly;
(2) dissolving casein phosphopeptide in water of 5-8 times, adding xylitol of 2-3 times of the weight of the casein phosphopeptide, uniformly mixing, ventilating the mixture at 60-70 ℃ for 2.5-3 hours, and uniformly mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) and (3) uniformly mixing the dried granules obtained in the last step with magnesium stearate to obtain a composition, and pressing the composition into tablets to obtain a preparation form of the tablets.
2. A composition according to claim 1, which is made from: 500 parts of kudzu root extract, 420-470 parts of glucosamine hydrochloride, 350-450 parts of calcium carbonate, 75-125 parts of chondroitin sulfate, 20-30 parts of casein phosphopeptide and a physiologically acceptable carrier.
3. A composition according to claim 1, which is made from: 500 parts of kudzu root extract, 440 parts of glucosamine hydrochloride, 400 parts of calcium carbonate, 100 parts of chondroitin sulfate, 25 parts of casein phosphopeptide and a physiologically acceptable carrier.
4. The composition according to claim 1, which is in the form of a tablet of chewable tablets.
5. The composition according to claim 1, wherein the xylitol is present in an amount of 600 to 900 parts by weight per 500 parts by weight of the puerariae radix extract.
6. The composition according to claim 1, wherein the xylitol is present in an amount of 700 to 800 parts by weight per 500 parts by weight of the puerariae radix extract.
7. The composition according to claim 1, wherein the amount of xylitol is 760 parts by weight per 500 parts by weight of the puerariae radix extract.
8. The composition according to claim 1, wherein the microcrystalline cellulose is present in an amount of 220 to 280 parts by weight per 500 parts by weight of the puerariae lobata extract.
9. The composition according to claim 1, wherein the microcrystalline cellulose is present in an amount of 240 to 260 parts by weight per 500 parts by weight of the puerariae lobata extract.
10. The composition according to claim 1, wherein the microcrystalline cellulose is present in an amount of 250 parts by weight per 500 parts by weight of the puerariae lobata extract.
11. The composition according to claim 1, wherein the amount of magnesium stearate is 22 to 28 parts by weight per 500 parts by weight of the puerariae radix extract.
12. The composition according to claim 1, wherein the amount of magnesium stearate is 24 to 26 parts by weight per 500 parts by weight of the puerariae radix extract.
13. A process for preparing a composition according to any one of claims 1 to 12, comprising the steps of:
(1) mixing radix Puerariae extract and glucosamine hydrochloride uniformly, and mixing calcium carbonate, chondroitin sulfate and glyceryl behenate uniformly;
(2) dissolving casein phosphopeptide in water of 5-8 times, adding xylitol of 2-3 times of the weight of the casein phosphopeptide, uniformly mixing, ventilating the mixture at 60-70 ℃ for 2.5-3 hours, and uniformly mixing;
(3) mixing the above two mixtures, adding microcrystalline cellulose and xylitol, mixing, adding water as lubricant, making into wet granule, and drying;
(4) and (3) uniformly mixing the dried granules obtained in the last step with magnesium stearate to obtain a composition, and pressing the composition into tablets to obtain a preparation form of the tablets.
14. Use of a composition according to any one of claims 1 to 12 in the manufacture of a product for increasing bone density, osteoarticular function and avoiding cramps in the waist and legs of the elderly.
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CN114532530A (en) * 2022-02-16 2022-05-27 浙江华方生命科技有限公司 Colostrum glucosamine chondroitin calcium chewable tablet and preparation method thereof

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