CN104524549A - Composition capable of improving joints and increasing bone mineral density and preparation method of composition - Google Patents

Abstract

The invention discloses a composition capable of improving joints and increasing bone mineral density and a preparation method of the composition. A Chinese herbal medicine extract which is refined from Chinese dwarf cherry by a modern extraction technology is scientifically compounded with other raw materials capable of increasing the bone mineral density, thus calcium absorption is effectively promoted from a plurality of aspects through comprehensive scientific combination and synergistic effect; cartilago articularis is repaired and rebuilt; synovial fluid is promoted to produce, synthesis of collagen in cartilago articularis matrix is promoted; further degeneration of cartilage is prevented; the osteoclast effect is indirectly weakened; re-absorption of bone is inhibited; the bone calcium content is increased; and the biomechanical property of the bone is improved, so that the composition has a good effect of increasing the bone mineral density. The integration and the biological stability of the composition can be further extracted by a microwave drying technology in the preparation method; the oxidation resistance of a grape seed extract in the raw material is improved; high adsorption and embedding effects of a dietary fiber and the antifungal properties of a Chinese herbal medicine extract are improved; and finally the composition which is efficient, safe, nutrient and stable, and has the function of increasing the bone mineral density is prepared.

Description

A kind of composition and method of making the same that there is joint-improving and increase bone density

Technical field

The present invention relates to compositions, be specifically related to a kind of composition and method of making the same that there is joint-improving and increase bone density.

Background technology

In recent years, osteoporosis has become a kind of disease of worldwide serious threat human health, and day by day causes the attention of people.At present, the whole world has sufferers of osteoporosis face more than 200,000,000, and its sickness rate has leapt to the 7th of the various commonly encountered diseases in the world.It has been generally acknowledged that, in west, in every 4 women or every 8 male, just have 1 to suffer from this disease.In the U.S., existing 1,000 ten thousand patients with osteoporosis and 1,800 ten thousand people may develop into the Low BMD patient of osteoporosis.Japan suffers from osteoporotic old people and has 900 ~ 1,000 ten thousand, accounts for 9% of Japanese total population.According to estimates, in the U.S., Europe and Japan, nearly 7,500 ten thousand people get involved, and wherein the overwhelming majority is postmenopausal women and most old people.China has progressively formed aged type society, and be the country that aging population are maximum in the world, will step into old peak period to the middle of this century, within more than 60 years old, old man accounts for 27% of total population, reaches more than 400,000,000 people.OP can cause pain, fracture, deformity, forfeiture independent living ability even dead, not only drastically influence the Health and Living quality of elderly population, and expends a large amount of manpower of state's family and home and financial resources, become socioeconomic significant burden.Along with life expectancy extends and population structure change, osteoporosis will become more serious public health problem.WHO specifies that annual June 24 was osteoporosis day, and China has also been classified as one of three large Senile disease of 12 state key tackling key problem.

Osteoporosis (osteoporosis, OP) refers to that in unit volume, bone amount reduces, so that the fine structure of bone changes, thus the class bone metabolism disease causing the increase of bone fragility even to be fractured.OP a kind ofly relates to everyone and with the chronic disease of continuous regression in people's a lot of year, has become the large disease threatening human health.OP can cause pain, fracture, deformity, forfeiture independent living ability even dead, not only drastically influence the Health and Living quality of elderly population, and expends a large amount of manpower of state's family and home and financial resources, become socioeconomic significant burden.

The OP cause of disease is illustrated so far not yet completely, and current medical circle thinks that hormone regulating and controlling, trophic factor, physical factor, immune function and inherited genetic factors are the reasons that OP occurs.Normal bone metabolism balance depends on the bone formation caused by osteoblast and these two processes of the bone resorption caused by osteoclast are in relative balance state.If due to the effect of above-mentioned factor, this poised state is destroyed, occurs that bone resorption is greater than bone formation, the loss of bone amount, bone structure just can be caused to change and the not congruent pathological change of bone matrix mineralising, thus cause osteoporosis.Therefore, osteoclast and osteoblastic differentiation are all the key links determining whether OP occurs with being formed.

The treatment of OP is a great problem of puzzlement medical circle always, there is no specific drug at present, have Hormone Replacement Therapy (HRT), selective estrogen receptor modulators (SERM), Bisphosphonates etc. to the Main Means of this disease for the treatment of in the world now.HRT is considered to the effective means of protect against osteoporosis always, but result of study display, and prolonged application HRT has to be increased patient cardiovascular system and to unify the risk that genital system tumor occurs.Other anti-OP medicines, comprise promoting bone growing and suppress the medicine of bone resorption, prolonged application all has obvious side effect, easily causes complication, or cuts because of uncertain therapeutic efficacy, and dosage is difficult to the shortcomings such as grasp, and range of application is narrow.The loss of calcium causes osteoporotic main cause, and therefore, traditional method adopts the method prevention and therapy osteoporosis of replenishing the calcium, but there are some researches show, replenishes the calcium merely and can not improve osteoporosis symptoms.

Clinical practice proves, many there is invigorating the liver and kidney, the natural drug of bone and muscle strengthening then can prevent and treat the clinical symptoms similar with OP effectively, safely, natural plants chemical substance-phytoestrogen is often rich in its effect preventing and treating OP with it relevant, as the selective estrogen receptor modulators that the soybean isoflavone in Semen sojae atricolor is natural, it is similar to raloxifene to osseous tissue effect, can prevent and treat the bone loss of menopausal women or ovariectomized rat.There is the chemical composition mainly compound such as lignin, flavonoid, diphenylethylene of phytoestrogen sample effect.The Cortex Eucommiae is the natural bone strengthening good medicine being rich in number of chemical material, and the bone disease of the clinical symptoms that its control is similar with OP has the history in over thousands of year.According to the literature, chemical composition mainly lignin, iridoids and the flavone compound of the Cortex Eucommiae, lignin and iridoids are its characteristic chemical constituents, its index composition pinoresinol diglucoside has short propagation and differentiation to osteoblast, find that its mechanism of action is after deliberation: lignin composition and endogenous estrogen are structurally comparatively similar, it has estrogen-like effects, thus promoting bone growing and suppression bone resorption.Domestic and international the experimental results shows, the Cortex Eucommiae has good preventive and therapeutic effect to osteoporosis.Research shows that Radix Puerariae, Herba Epimedii also have bibliographical information to regulate hormonal readiness, there is the effect increasing bone density, chondroitin sulfate, bone collagen also can improve osteoporosis symptoms, improve function of joint, owing to there is antagonism or synergism after multi-medicament combination, also other toxic and side effects may be had.

Dimethyl sulfone (MSM) is a kind of organic sulfur compound, is the necessary goods and materials of human collagen albumen synthesis.Dimethyl sulfone can ease pain.It can stop the propagation of pain nerve signal, also can improve collagen and connect, repair injured tissue.Zoopery proves, dimethyl sulfone can contain kneed deterioration really, also can increase the effect of hydrocortisone, instead of quantity.Hydrocortisone is the natural anti-inflammatory hormone in human body.Dimethyl sulfone can also be suppressed to fibrocellular generation, and fibroblast is then the principal element causing edema.Finally, dimethyl sulfone can also combine with the liquid in swollen tissue, thus detumescence.In human body and zoopery, dimethyl sulfone be used alone or with other supplementarys, particularly tie up with bone element (glucosamine sulfate) together with use, therapeutical effect can be had to arthritis.Be published in the Control release of the randomized, double-blind on " clinical drug research " (Clinical Drug Investigation) and mention, the plain dimethyl sulfone of adding 500 milligrams of bone dimension of 500 milligrams can palliate the agonizing sufferings and swelling better, recover the mobility in joint, and resume speed sooner, more comprehensively.

Chinese patent CN 102218089 B discloses a kind of Chinese medicine preparation, particularly there is the Chinese medicine preparation increasing bone density, improve osteoporosis and arthralgia function, this Chinese medicine preparation contains Herba Epimedii extract, Radix Salviae Miltiorrhizae extract, D-Glucosamine Hydrochloride, biological calcium carbonate (Concha Ostreae calcium), hydrolytic collagen, chondroitin sulfate isoreactivity composition, and wherein D-ammonia glucosamine salt hydrochlorate significantly can promote that Herba Epimedii extract and Radix Salviae Miltiorrhizae extract are to the effect of osteoblastic proliferation, differentiation.Said preparation bases oneself upon traditional Chinese medicine theory and studies in conjunction with modern medicine, replenished the calcium and ossein by liver and kidney tonifying, strengthening kidney and tonifying bone, promoting blood circulation to remove obstruction in the collateral and direct biology, make kidney qi abundance, bone foster to some extent, improve osteodynia and arthralgia, improve quality of life climacteric, thus play the effect increasing bone density, improve osteoporosis and arthralgia.Chinese patent CN 101559218 B discloses a kind of composition and method of making the same with increase bone substance density improving function.Active component contained by it is calcium carbonate, glucosamine hydrochloride, chondroitin sulfate, phosphopeptide caseinate, soybean isoflavone; The present invention is by above-mentioned raw materials rationally scientifically assembly, is made into oral formulations, said preparation taking convenience, the experiment proved that to have increase bone substance density improving function.Chinese patent CN 103798595 A discloses a kind of health food increasing bone density, it comprises the raw material of following weight portion: the Cortex Eucommiae 3-10, Radix Puerariae 4-10, Herba Epimedii 3-10, vitamin D3 0.000002-0.00001, chondroitin sulfate 0.3-1.5, calcium carbonate 0.3-1.5, collagen protein 0.2-1; Described health food also comprises adjuvant, and adjuvant weight is 6-10 of health food gross weight.This health food can increase bone density, and for osteoporosis and improve osteoarthrosis function, its effect is than being used alone the much effective of the Cortex Eucommiae, Radix Puerariae, Herba Epimedii, chondroitin sulfate or bone collagen.Chinese patent CN 101248882 B mono-kind has the nutraceutical promoting skeleton and bony articulation health, by calcium carbonate 11.11 ~ 22.22%, phosphopeptide caseinate 1.48 ~ 2.96%, glucosamine hydrochloride 11.11 ~ 16.67%, collagen protein 6.66 ~ 11.11%, microcrystalline Cellulose 12 ~ 56.6%, magnesium stearate 0.24 ~ 0.57%, chondroitin sulfate 3.33 ~ 11.11%, dimethyl sulfone 2.22 ~ 7.77%, magnesium lactate 6 ~ 12%, Semen Vitis viniferae extract 0.56 ~ 1.33%, vitaminB10 .01 ~ 0.02%, vitamin B2 0.01 ~ 0.02%, vitamin C 0.67 ~ 2.22% forms, have and prevent, delaying osteoporosis, prevent arthritis, repair joint protecting film, improve joint mobility, promote regenerating bone or cartilage, analgesia, anti-oxidation, prevent the generation of oxygen-derived free radicals, delay effect of body aging.

The product curative effect of above-mentioned disclosed increase bone density is also very undesirable, there is following defect: the Chinese herbal medicine extract Chinese herbal medicine formula 1) used is simple, synergism is not comprehensive; 2) Chinese herbal medicine extract uses conventional methods preparation, and effective component extraction rate is low, causes wastage of material, and cost raises, and foodsafety is low; 3) the calcium source disclosed in product is mainly based on the inorganic calciums such as calcium carbonate or organic calcium, it all adopts the method extracting and developing of chemistry or synthesis to prepare, there is certain food safety hidden danger, the application of calcium carbonate can have side effects to the patient of easy flatulence, calcium source single property; 4) stability problem of product is not well solved.

China's Cerasus humilis Bunge fruit contains the nutrient substance such as abundant sugar, protein, mineral element, vitamin, aminoacid, especially the content of calcium and ferrum is very high, in fresh fruit, calcium content can reach 60mg/100g, iron content 1.5mg/100g (Fructus Mali pumilae is respectively 9mg/100g and 0.24mg/100g).Containing 17 seed amino acids in fruit, total amount reaches 338.3-451.7mg/100g, and wherein children growth essential amino acids content is up to 102.7-126.6mg/100g, especially lysine, valine, leucine and isoleucine content are very high, because of but the health fruit of child and old man.Containing total sugar 5.20% in Cerasus humilis Bunge fruit, reducing sugar 3.38%, organic acid 1.31%, has Vc6.17 milligram/100 gram.The kernel of Cerasus humilis Bunge has the function of detumescence, diuresis, relieving constipation, and be a kind of well medical material, medical industry also can be processed.The stem and leaf of Cerasus humilis Bunge can feed cattle, can utilize the feature that its Biomass is large, drives the development of animal husbandry.

By natural food material---Chinese Cerasus humilis Bunge is applied to the product increasing bone density, not only can be that product provides that abundant foodsafety is high, calcium content is high, calcium utilization and the high natural plant calcium source of absorbance and other nutrient substance, but also the development of the industries such as animal husbandry can be driven, realize sustainable development, at present, yet there are no the report Chinese Cerasus humilis Bunge being applied to and increasing bone density product.

Summary of the invention

Technical problem solved by the invention is the defect overcoming existing increase bone density product, by natural plant calcium source---Chinese Cerasus humilis Bunge with adopt modern multiple extractive technique and refining Chinese herbal medicine extract and other to have the raw material science increasing bone substance density improving function composite, prepare the compositions of a kind of safety, nutrition, efficient, stable increase bone density.

In order to achieve the above object, the present invention is by the following technical solutions:

Have a compositions for joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 20-50 part, Chinese herbal medicine extract 12-30 part, Cerasus humilis Bunge extract 15-25 part, Glucosamine sulfate potassium chloride 5-15 part, chondroitin sulfate 5-10 part, milk calcium 2-10 part, Calcium peptide of casein 2.5-8 part, magnesium lactate 3-6 part, dimethyl sulfone 2-4 part, Semen Vitis viniferae extract 1.5-4 part, zinc lactate 0.15-0.3 part;

Preferably, described in there is joint-improving and increase the compositions of bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 30-40 part, Chinese herbal medicine extract 15-25 part, Cerasus humilis Bunge extract 18-23 part, Glucosamine sulfate potassium chloride 8-12 part, chondroitin sulfate 7-9 part, milk calcium 5-8 part, Calcium peptide of casein 4-6 part, magnesium lactate 4-5.5 part, dimethyl sulfone 2.5-3.5 part, Semen Vitis viniferae extract 2-3.5 part, zinc lactate 0.18-0.25 part;

More preferably, described in there is joint-improving and increase the compositions of bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 35 parts, Chinese herbal medicine extract 20 parts, Cerasus humilis Bunge extract 20 parts, Glucosamine sulfate potassium chloride 10 parts, chondroitin sulfate 8 parts, milk calcium 7 parts, Calcium peptide of casein 5 parts, magnesium lactate 4.8 parts, dimethyl sulfone 3 parts, Semen Vitis viniferae extract 2.8 parts, zinc lactate 0.21 part;

Further, described in there is joint-improving and increase the compositions of bone density, also comprise the adjuvant of following parts by weight:

Maltodextrin 5-20 part, D-mannital 5-20 part, modified dietary fiber 5-20 part, guar gum 2-10 part, hydroxypropyl emthylcellulose 0.5-1.5 part, citric acid 0.5-1.5 part, silicon dioxide 0.2-1 part, stevioside 0.01-0.15 part;

Preferably, described in there is joint-improving and increase the compositions of bone density, also comprise the adjuvant of following parts by weight:

Maltodextrin 10-18 part, D-mannital 8-15 part, modified dietary fiber 15-18 part, guar gum 4-6 part, hydroxypropyl emthylcellulose 0.8-1.2 part, citric acid 0.8-1.2 part, silicon dioxide 0.4-0.6 part, stevioside 0.06-0.12 part;

More preferably, described in there is joint-improving and increase the compositions of bone density, also comprise the adjuvant of following parts by weight:

Maltodextrin 14 parts, D-mannital 11 parts, modified dietary fiber 17 parts, guar gum 5 parts, hydroxypropyl emthylcellulose 1 part, citric acid 1 part, silicon dioxide 0.5 part, stevioside 0.08 part.

Further, described Chinese herbal medicine extract is prepared through ultrasonic cleaning, low temperature enzymolysis, water extraction alcohol extraction and microwave-assisted supersound extraction for raw material with Rhizoma Drynariae, Herba Epimedii, Fructus Lycii;

Preferably, the preparation method of described Chinese herbal medicine extract comprises the steps: to count by weight, takes Rhizoma Drynariae 5-12 part, Herba Epimedii 5-12 part, Fructus Lycii 3-8 part, put in the ultrasonic washing unit filling 0.1-0.3% sodium bicarbonate solution in 200W, 30KHz cleans 10-15min, drain, said herbal medicine being crushed to particle diameter is less than 2 millimeters, put Homogeneous phase mixing in container and add the water of 3-6 times of weight, obtain mixed material, control temperature 70 DEG C-90 DEG C keeps 2-4h, then 40-50 DEG C is cooled to, be 3.5-4.5 by lactic acid adjust ph, at power 150-300W, microwave extraction is carried out under frequency 2000Hz condition, wherein, each microwave exposure total time 60-80s, carry out compartment irradiation: irradiation 10s, interval 10s, irradiation like this 10 times, simultaneously at power 200-300W, ultrasonic assistant extraction is carried out under frequency 30-40KHz condition, then the mixing enzyme preparation adding mixed material gross weight 3-7% carries out enzymolysis, be 5.5-6.8 by lactic acid adjust ph, enzymolysis 2-4h, finally add the mixture of mixed material 0.5-3 times of w ethanol and propanol, the mass ratio of ethanol and propanol mixing is 1:1-3, control temperature to 60 DEG C-78 DEG C of maintenance 3-4h, filter, obtain the first filtrate, add the water of filtering residue 1-3 times of weight, control temperature 85 DEG C-95 DEG C keeps 1-3h, is then cooled to 25-35 DEG C, filters, obtains the second filtrate, first filtrate and the second filtrate are merged according to mass ratio 2-4:1-3, filter vacuum concentrates postlyophilization, pulverizes and obtains Chinese herbal medicine extract,

Described mixed enzyme is glucanase, xylanase, pentosanase, pectase 2-4:2-4:1-3:1-2 Homogeneous phase mixing in mass ratio.

Further, described Cerasus humilis Bunge extract is with Chinese Cerasus humilis Bunge fresh fruit for raw material, adopts ultrasonic cleaning, microwave-assisted supersound extraction, high-pressure pulse electric to extract and prepare through natural fermentation;

Preferably, the preparation method of described Cerasus humilis Bunge extract comprises the steps: Chinese Cerasus humilis Bunge fresh fruit to put in the ultrasonic washing unit filling 0.8-1.2% sodium bicarbonate solution in 200W, 30KHz cleans 10-15min, drain, pulverize immediately after-18--22 DEG C of freezing 1-2h, freezing thickness of feed layer 3-5cm, powder particle diameter 0.5-3mm, then add and pulverize raw materials quality 0.5-2 water doubly, be 3.0-3.5 by lactic acid adjust ph, at power 200-300W, microwave extraction is carried out under frequency 2000Hz condition, wherein, each microwave exposure total time 100-120s, carry out compartment irradiation: irradiation 10s, interval 10s, control temperature 20-35 DEG C, irradiation like this 10 times, simultaneously at power 200-300W, ultrasonic assistant extraction is carried out under frequency 30-40KHz condition, insulation 1-3h, then, microwave extraction is carried out under power 200-400W, frequency 2000Hz condition, wherein, each microwave exposure total time 120-135s, carry out compartment irradiation: irradiation 15s, interval 10s, control temperature 40-50 DEG C, irradiation like this 10 times, simultaneously at power 300-500W, carry out ultrasonic assistant extraction under frequency 40-50KHz condition, last Temperature fall to room temperature, in electric field intensity 15-25kV/cm, burst length 300-500 μ s, carries out high-pressure pulse electric (PEF) and extracts 15-20min under pulse frequency 200-300Hz condition, abundant stirring extracting solution, sealing, natural fermentation 4-10d, filtering fermentation liquor obtains the first filtrate, add the water rinse of filtering residue 2 times, filter to obtain the second filtrate, by the first filtrate and the second filtrate 1:2-5 Homogeneous phase mixing in mass ratio, namely mixed liquor ultrafiltration and concentration, lyophilization, 30 DEG C of pulverize at low temperature obtain Cerasus humilis Bunge extract to particle diameter 0.1-0.3mm.

Further, described modified dietary fiber is that the soluble fiber cellulose content obtained through physics, chemistry or biological method process by dietary fiber is high, biological activity is strong has cellulose that is important, positive role to beneficial bacteria of intestinal tract group, compared with full diet fiber, its biological action is more powerful: 1) soluble fiber cellulose content is high, more easily utilized by probiotic bacteria, improve probiotic bacteria in the growth of intestinal and fertility, increase kind and the quantity of probiotic bacteria flora, reduce large intestine pH value, improve intestine microenvironment; 2) powerful absorbability, through modified, cellulosic specific surface area increases, and network is enriched, and absorption affinity strengthens, and the organic molecule ability of chelating, absorption cholesterol and bile acids is stronger, suppress human body to their absorption; 3) ion-exchange capacity strengthens, and to metallic element, particularly heavy metal element adsorption effect is stronger; 3) the stronger and impact of acid and alkali, alkali, salt of retentiveness, dilatancy, thickening property;

Preferably, described modified dietary fiber is obtained through enzyme enzymolysis by one or more in inulin, apple fiber, Herba avenae fatuae fiber, Semen Tritici aestivi fiber, Testa oryzae, wheat bran;

More preferably, the preparation method of described modified dietary fiber comprises the following steps: by inulin, apple fiber, Herba avenae fatuae fiber, Semen Tritici aestivi fiber, Testa oryzae, wheat bran 8-10:4-7:3-5:2-4:1-3:1-2 Homogeneous phase mixing in mass ratio, add its quality 3-7 water doubly, room temperature 200-300W, 35-40KHz condition supersound extraction 10-15min, simultaneously in electric field intensity 20-40kV/cm, burst length 400-500 μ s, carries out high-pressure pulse electric extraction under pulse frequency 200-300Hz condition; Be 4.5-6.5 by lactic acid adjust ph, add the enzyme of mixture quality 0.1-0.3%, in 45-55 DEG C of enzymolysis 20-48min; Enzymolysis solution concentrating under reduced pressure, lyophilization, pulverize at low temperature to particle diameter are that namely 0.1-0.3mm obtains modified dietary fiber;

Described enzyme is xylanase, cellulase, laccase, pectase, tannase, amylase and protease 6-10:4-8:3-5:2-4:1-3:1-3:0.3-0.5 Homogeneous phase mixing in mass ratio.

The compositions that the present invention has joint-improving and increase bone density can be prepared by the following method, comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 60-120 mesh sieve, then mix 8-25min, obtain mixed powder;

2) by maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, the stevioside aqueous solution making 13-18% soluble in water, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 10-20 mesh sieve, obtain wet granular, put in power 3000W, frequency 2000Hz, temperature 55-65 DEG C dry 3-8min in microwave dryer, with the quick granulate of 10-20 mesh sieve;

4) whole good granule and silicon dioxide mixing 5-10min, namely mix homogeneously obtains compositions.

The dosage form of the present composition is oral formulations, can be powder, capsule, tablet or granule, is preferably powder and capsule.The bioavailability of described powder is high, is convenient to absorb and utilize, and ensures the result of use of product.Described capsule has can cover raw material bitterness, and it is clean and tidy, attractive in appearance, easily swallow, and can improve drug stabilisation, product design is attractive in appearance, carries, taking convenience.

The present invention also provides the preparation method of above-mentioned composition, and it comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 60-120 mesh sieve, then mix 8-25min, obtain mixed powder;

2) by maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, the stevioside aqueous solution making 13-18% soluble in water, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 10-20 mesh sieve, obtain wet granular, put in power 3000W, frequency 2000Hz, temperature 55-65 DEG C dry 3-8min in microwave dryer, with the quick granulate of 10-20 mesh sieve;

4) whole good granule and silicon dioxide mixing 5-10min, after mix homogeneously, make powder, capsule, tablet or granule.

Preferably, the preparation method of compositions powder of the present invention comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 100 mesh sieves, then mix 18min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 15% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 16 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, the dry 5min of temperature 60 C in microwave dryer, with the quick granulate of 16 mesh sieve;

4) whole good granule and silicon dioxide mixing 8min, after mix homogeneously, pulverizes, crosses 100 mesh sieves, subpackage, the obtained powder of sealing.

Preferably, the preparation method of composition capsule of the present invention comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 100 mesh sieves, then mix 18min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 15% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 16 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, the dry 5min of temperature 60 C in microwave dryer, with the quick granulate of 16 mesh sieve;

4) whole good granule and silicon dioxide mixing 8min, after mix homogeneously, dress grain, selects capsule, polishing, makes capsule.

Another object of the present invention has joint-improving and increases the compositions of bone density and preparing the application in food, health product or medicine described in being.

Beneficial effect:

1. the present invention has the compositions of joint-improving and increase bone density is according to Chinese medicine health preserving, health care achievement in research that is theoretical and modern pharmacology develops, the kidney invigorating bone strengthening will be had, continuous Rhizoma Drynariae of hindering pain relieving, the Herba Epimedii of invigorating the kidney and strengthening the bones, the kidney invigorating nourishing the liver, antidotal Fructus Lycii scientific compatibility also adopts modern advanced extractive technique to prepare the Chinese herbal medicine extract having and efficiently increase bone density, and with can suppress to destroy chondrocyte in order to avoid cartilage is decomposed or dissolves thus prevent the chondroitin sulfate of bone sclerosis, effectively can promote the absorption of calcium and can promote that skeleton is to the utilization of calcium, the Glucosamine sulfate potassium chloride of releasing osteoporosis symptom, Calcium peptide of casein, analgesia pain relieving, contain kneed deterioration, recover the dimethyl sulfone of function of joint, combine the important trace element magnesium promoting calcium absorption, zinc, natural, safety, easy to digest, the Cerasus humilis Bunge extract of easy absorption, effective elimination free radical, improve the Semen Vitis viniferae extract of immunity, improve beneficial bacteria of intestinal tract group field planting, improve intestine microenvironment, promote the comprehensive scientific combination such as the modified dietary fiber of absorption of nutrient ingredients, synergism, effectively promote the absorption of calcium from many aspects, repair and reconstruction articular cartilage, expedite the emergence of knuckle synovia, promote the synthesis of collagen in articular cartilage matrix, cartilage is stoped to be degenerated further, indirectly weaken osteoclast effect and suppress absorbing again of bone, increase calcium content of bone, improve bone biomechanical property, product is made to have the effect well increasing bone density.Finally prepare a kind of efficient, safety, nutrition, stable there is the compositions increasing bone substance density improving function.

2. the modern advanced such as ultrasonic cleaning, biological enzymolysis, microwave extraction, supersound extraction and high-pressure pulse electric extraction combine by Chinese herbal medicine extract, the Cerasus humilis Bunge extract that prepared by the present invention, the drug effect not only increasing raw material availability, reduce compositions cost, improve compositions, the more important thing is the pesticide residues, the heavy-metal residual that effectively eliminate plant material and killed remaining worm's ovum, improve the foodsafety of compositions.

3. the modified dietary fiber prepared of the present invention is compared with full diet fiber, its biological action is more powerful: 1) soluble fiber cellulose content is high, more easily utilized by probiotic bacteria, improve probiotic bacteria in the growth of intestinal and fertility, increase kind and the quantity of probiotic bacteria flora, reduce large intestine pH value, improve intestine microenvironment; 2) powerful absorbability, through modified, cellulosic specific surface area increases, and network is enriched, and absorption affinity strengthens, and the organic molecule ability of chelating, absorption cholesterol and bile acids is stronger, suppress human body to their absorption; 3) ion-exchange capacity strengthens, and to metallic element, particularly heavy metal element adsorption effect is stronger; 3) the stronger and impact of acid and alkali, alkali, salt of retentiveness, dilatancy, thickening property.

4. to have the preparation method technique of the compositions increasing bone density effect simple in the present invention; be produced on a large scale; microwave drying technology wherein can further improve amalgamation and the biological stability of compositions; add Semen Vitis viniferae extract non-oxidizability in raw material, the powerful absorption of modified dietary fiber and bury function, compositions that the antagonistic property of Chinese herbal medicine extract makes the present invention prepare are more stable, extend the shelf-life of compositions.

Detailed description of the invention

The present invention is described below by specific embodiment.Unless stated otherwise, technological means used in the present invention is method known in those skilled in the art.In addition, embodiment is interpreted as illustrative, but not limits the scope of the invention, and the spirit and scope of the invention only limited by claims.To those skilled in the art, under the prerequisite not deviating from essence of the present invention and scope, the various change carry out the material component in these embodiments and consumption or change also belong to protection scope of the present invention.

Prepared by embodiment 1 raw material

1. the preparation of Chinese herbal medicine extract

The preparation method of described Chinese herbal medicine extract comprises the steps: to count by weight, takes Rhizoma Drynariae 8 parts, Herba Epimedii 10 parts, Fructus Lycii 5 parts, put in the ultrasonic washing unit filling 0.2% sodium bicarbonate solution in 200W, 30KHz cleans 12min, drain, said herbal medicine being crushed to particle diameter is less than 2 millimeters, put Homogeneous phase mixing in container and add the water of 5 times of weight, obtain mixed material, control temperature 80 DEG C keeps 3h, then 45 DEG C are cooled to, be 4 by lactic acid adjust ph, at power 200W, microwave extraction is carried out under frequency 2000Hz condition, wherein, each microwave exposure total time 70s, carry out compartment irradiation: irradiation 10s, interval 10s, irradiation like this 10 times, simultaneously at power 300W, ultrasonic assistant extraction is carried out under frequency 35KHz condition, then the mixing enzyme preparation adding mixed material gross weight 5% carries out enzymolysis, be 6.2 by lactic acid adjust ph, enzymolysis 3h, finally add the mixture of mixed material 2 times of w ethanol and propanol, the mass ratio of ethanol and propanol mixing is 1:2, control temperature to 70 DEG C keeps 4h, filters, obtains the first filtrate, add the water of filtering residue 2 times of weight, control temperature 90 DEG C keeps 2h, is then cooled to 30 DEG C, filters, obtains the second filtrate, first filtrate and the second filtrate are merged according to mass ratio 3:2, filter vacuum concentrates postlyophilization, pulverizes and obtains Chinese herbal medicine extract,

Described mixed enzyme is glucanase, xylanase, pentosanase, pectase 3:3:2:1.5 Homogeneous phase mixing in mass ratio.

2. the preparation of Cerasus humilis Bunge extract

The preparation method of described Cerasus humilis Bunge extract comprises the steps: Chinese Cerasus humilis Bunge fresh fruit to put in the ultrasonic washing unit filling 1% sodium bicarbonate solution in 200W, 30KHz cleans 12min, drain, pulverize immediately after-20 DEG C of freezing 1.5h, freezing thickness of feed layer 4cm, powder particle diameter 1.5mm, then the water pulverizing raw materials quality 1.5 times is added, be 3.2 by lactic acid adjust ph, at power 200W, microwave extraction is carried out under frequency 2000Hz condition, wherein, each microwave exposure total time 110s, carry out compartment irradiation: irradiation 10s, interval 10s, control temperature 28 DEG C, irradiation like this 10 times, simultaneously at power 300W, ultrasonic assistant extraction is carried out under frequency 35KHz condition, insulation 2h, then, microwave extraction is carried out under power 300W, frequency 2000Hz condition, wherein, each microwave exposure total time 125s, carry out compartment irradiation: irradiation 15s, interval 10s, control temperature 45 DEG C, irradiation like this 10 times, simultaneously at power 400W, carry out ultrasonic assistant extraction under frequency 45KHz condition, last Temperature fall to room temperature, in electric field intensity 20kV/cm, burst length 400 μ s, carries out high-pressure pulse electric (PEF) and extracts 18min under pulse frequency 250Hz condition, abundant stirring extracting solution, sealing, natural fermentation 7d, filtering fermentation liquor obtains the first filtrate, add the water rinse of filtering residue 2 times, filter to obtain the second filtrate, by the first filtrate and the second filtrate 1:3 Homogeneous phase mixing in mass ratio, namely mixed liquor ultrafiltration and concentration, lyophilization, 30 DEG C of pulverize at low temperature obtain Cerasus humilis Bunge extract to particle diameter 0.2mm.

3. the preparation of modified dietary fiber

The preparation method of described modified dietary fiber comprises the following steps: by inulin, apple fiber, Herba avenae fatuae fiber, Semen Tritici aestivi fiber, Testa oryzae, wheat bran 9:6:4:3:2:1.5 Homogeneous phase mixing in mass ratio, add the water of its quality 5 times, room temperature 300W, 40KHz condition supersound extraction 12min, simultaneously in electric field intensity 30kV/cm, burst length 500 μ s, carries out high-pressure pulse electric extraction under pulse frequency 300Hz condition; Be 5.5 by lactic acid adjust ph, add the enzyme of mixture quality 0.2%, in 50 DEG C of enzymolysis 35min; Enzymolysis solution concentrating under reduced pressure, lyophilization, pulverize at low temperature to particle diameter are that namely 0.2mm obtains modified dietary fiber;

Described enzyme is xylanase, cellulase, laccase, pectase, tannase, amylase and protease 8:6:4:3:2:2:0.4 Homogeneous phase mixing in mass ratio.

The Chinese herbal medicine extract that following embodiment 2-8 uses, Cerasus humilis Bunge extract, modified dietary fiber are embodiment 1 to be prepared, and other is commercial commodity.

Embodiment 2

Have a powder for joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 35 parts, Chinese herbal medicine extract 20 parts, Cerasus humilis Bunge extract 20 parts, Glucosamine sulfate potassium chloride 10 parts, chondroitin sulfate 8 parts, milk calcium 7 parts, Calcium peptide of casein 5 parts, magnesium lactate 4.8 parts, dimethyl sulfone 3 parts, Semen Vitis viniferae extract 2.8 parts, zinc lactate 0.21 part;

The described powder having joint-improving and increase bone density, also comprises the adjuvant of following parts by weight:

Maltodextrin 14 parts, D-mannital 11 parts, modified dietary fiber 17 parts, guar gum 5 parts, hydroxypropyl emthylcellulose 1 part, citric acid 1 part, silicon dioxide 0.5 part, stevioside 0.08 part.

Preparation method comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 100 mesh sieves, then mix 18min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 15% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 16 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, the dry 5min of temperature 60 C in microwave dryer, with the quick granulate of 16 mesh sieve;

4) whole good granule and silicon dioxide mixing 8min, after mix homogeneously, pulverizes, crosses 100 mesh sieves, subpackage, the obtained powder of sealing.

Embodiment 3

Have a powder for joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 20 parts, Chinese herbal medicine extract 12 parts, Cerasus humilis Bunge extract 15 parts, Glucosamine sulfate potassium chloride 5 parts, chondroitin sulfate 5 parts, milk calcium 2 parts, Calcium peptide of casein 2.5 parts, magnesium lactate 3 parts, dimethyl sulfone 2 parts, Semen Vitis viniferae extract 1.5 parts, zinc lactate 0.15 part;

The described powder having joint-improving and increase bone density, also comprises the adjuvant of following parts by weight:

Maltodextrin 5 parts, D-mannital 5 parts, modified dietary fiber 5 parts, guar gum 2 parts, hydroxypropyl emthylcellulose 0.5 part, citric acid 0.5 part, silicon dioxide 0.2 part, stevioside 0.01 part;

Preparation method, comprises the following steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 60 mesh sieves, then mix 8min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 13% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 10 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, temperature 55 DEG C of dry 3min in microwave dryer, with the quick granulate of 10 mesh sieve;

4) whole good granule and silicon dioxide mixing 5min, after mix homogeneously, pulverizes, crosses 100 mesh sieves, subpackage, the obtained powder of sealing.

Embodiment 4

Have a powder for joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 50 parts, Chinese herbal medicine extract 30 parts, Cerasus humilis Bunge extract 25 parts, Glucosamine sulfate potassium chloride 15 parts, chondroitin sulfate 10 parts, milk calcium 10 parts, Calcium peptide of casein 8 parts, magnesium lactate 6 parts, dimethyl sulfone 4 parts, Semen Vitis viniferae extract 4 parts, zinc lactate 0.3 part;

The described powder having joint-improving and increase bone density, also comprises the adjuvant of following parts by weight:

Maltodextrin 20 parts, D-mannital 20 parts, modified dietary fiber 20 parts, guar gum 10 parts, hydroxypropyl emthylcellulose 1.5 parts, citric acid 1.5 parts, silica 1 part, stevioside 0.15 part;

Preparation method, comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 120 mesh sieves, then mix 25min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 18% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 20 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, temperature 65 DEG C of dry 8min in microwave dryer, with the quick granulate of 20 mesh sieve;

4) whole good granule and silicon dioxide mixing 10min, after mix homogeneously, pulverizes, crosses 100 mesh sieves, subpackage, the obtained powder of sealing.

Embodiment 5

Have a capsule for joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 30 parts, Chinese herbal medicine extract 15 parts, Cerasus humilis Bunge extract 18 parts, Glucosamine sulfate potassium chloride 8 parts, chondroitin sulfate 7 parts, milk calcium 5 parts, Calcium peptide of casein 4 parts, magnesium lactate 4 parts, dimethyl sulfone 2.5 parts, Semen Vitis viniferae extract 2 parts, zinc lactate 0.18 part;

The described capsule having joint-improving and increase bone density, also comprises the adjuvant of following parts by weight:

Maltodextrin 10 parts, D-mannital 8 parts, modified dietary fiber 15 parts, guar gum 4 parts, hydroxypropyl emthylcellulose 0.8 part, citric acid 0.8 part, silicon dioxide 0.4 part, stevioside 0.06 part;

Preparation method, comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 100 mesh sieves, then mix 18min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 15% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 20 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, the dry 5min of temperature 60 C in microwave dryer, with the quick granulate of 16 mesh sieve;

4) whole good granule and silicon dioxide mixing 8min, after mix homogeneously, dress grain, selects capsule, polishing, makes capsule.

Embodiment 6

Have a capsule for joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 40 parts, Chinese herbal medicine extract 25 parts, Cerasus humilis Bunge extract 23 parts, Glucosamine sulfate potassium chloride 12 parts, chondroitin sulfate 9 parts, milk calcium 8 parts, Calcium peptide of casein 6 parts, magnesium lactate 5.5 parts, dimethyl sulfone 3.5 parts, Semen Vitis viniferae extract 3.5 parts, zinc lactate 0.25 part;

The described capsule having joint-improving and increase bone density, also comprises the adjuvant of following parts by weight:

Maltodextrin 18 parts, D-mannital 15 parts, modified dietary fiber 18 parts, guar gum 6 parts, hydroxypropyl emthylcellulose 1.2 parts, citric acid 1.2 parts, silicon dioxide 0.6 part, stevioside 0.12 part;

Preparation method, comprises the following steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 60 mesh sieves, then mix 8min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 13% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 10 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, temperature 55 DEG C of dry 3min in microwave dryer, with the quick granulate of 10 mesh sieve;

4) whole good granule and silicon dioxide mixing 5min, after mix homogeneously, dress grain, selects capsule, polishing, makes capsule.

Embodiment 7

Have a tablet for joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 35 parts, Chinese herbal medicine extract 20 parts, Cerasus humilis Bunge extract 20 parts, Glucosamine sulfate potassium chloride 10 parts, chondroitin sulfate 8 parts, milk calcium 7 parts, Calcium peptide of casein 5 parts, magnesium lactate 4.8 parts, dimethyl sulfone 3 parts, Semen Vitis viniferae extract 2.8 parts, zinc lactate 0.21 part;

The described tablet having joint-improving and increase bone density, also comprises the adjuvant of following parts by weight:

Maltodextrin 14 parts, D-mannital 11 parts, modified dietary fiber 17 parts, guar gum 5 parts, hydroxypropyl emthylcellulose 1 part, citric acid 1 part, silicon dioxide 0.5 part, stevioside 0.08 part.

Preparation method comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 100 mesh sieves, then mix 18min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 15% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 16 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, the dry 5min of temperature 60 C in microwave dryer, with the quick granulate of 16 mesh sieve;

4) whole good granule and silicon dioxide mixing 8min, after mix homogeneously, namely tabletting, film coating obtain tablet.

Embodiment 8

Have a granule for joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight:

Calcium lactate 35 parts, Chinese herbal medicine extract 20 parts, Cerasus humilis Bunge extract 20 parts, Glucosamine sulfate potassium chloride 10 parts, chondroitin sulfate 8 parts, milk calcium 7 parts, Calcium peptide of casein 5 parts, magnesium lactate 4.8 parts, dimethyl sulfone 3 parts, Semen Vitis viniferae extract 2.8 parts, zinc lactate 0.21 part;

The described granule having joint-improving and increase bone density, also comprises the adjuvant of following parts by weight:

Maltodextrin 14 parts, D-mannital 11 parts, modified dietary fiber 17 parts, guar gum 5 parts, hydroxypropyl emthylcellulose 1 part, citric acid 1 part, silicon dioxide 0.5 part, stevioside 0.08 part.

Preparation method comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 100 mesh sieves, then mix 18min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 15% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 16 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, the dry 5min of temperature 60 C in microwave dryer, with the quick granulate of 16 mesh sieve;

4) whole good granule packs, seals and obtain granule.

By following verification experimental verification the present invention, there is increase bone substance density improving function:

One, animal experiment

1. experiment purpose

Study the effect that the compositions with joint-improving and increase bone substance density improving function of the present invention increases bone density

2. Experimental agents

By the compositions (powder) with joint-improving and increase bone substance density improving function that specific embodiment 2 prepares.

3. laboratory animal

SPF level rat, female, Chinese Medical Sciences University's Experimental Animal Center provides.

4. experimental technique and result

Choose healthy SD rat 140, be female entirely, body weight 200 ± 20g, first carries out modeling process.Rat is through the anesthesia of lumbar injection 50mg/kg pentobarbital sodium, and in ventrimeson apart from vaginal orifice 3 ~ 4cm place unhairing after abdomen position is fixing, sterilization, by the silk thread ligation of fallopian tube under ovary, wipes out ovary, wipe out another side ovary with method.Rat is divided into groups at random, be respectively Normal group, model control group, what specific embodiment 2 was obtained have joint-improving and it is (low to increase the compositions group powder of bone substance density improving function, in and high dose group), Cerasus humilis Bunge extract group and Chinese herbal medicine extract group, described Cerasus humilis Bunge extract group refers in the embodiment of the present invention 2 powder prepared by other component removing Cerasus humilis Bunge extract, what described Chinese herbal medicine extract group referred to that Chinese herbal medicine extract in the embodiment of the present invention 2 adopts is traditional water extraction, the powder that Chinese herbal medicine extract prepared by alcohol extracting method is prepared with other component, often organize 18 ~ 20 Mus.Respectively each group of rat is weighed, numbering, and carry out administration by the dosage in table 1.

Weekly according to the body weight change adjustment dosage of rat.

After 6 months, measure the BMD value of the bone density of each group of rat, femur weight in wet base, wet density, dry density, measurement result is as shown in table 1:

Table 1 has joint-improving and increases the powder of bone substance density improving function affects result to ovariectomized female rats bone density BMD

Group

Quantity (only)

Dosage mg/kg *bw

Neck of femur

Femur mid point

Femur distal end

Model control group	16	Equal-volume	0.2698±0.0412	0.2735±0.0247	0.2608±0.0187
						Normal group	17	Equal-volume	0.3253±0.0193 ***	0.3208±0.0519	0.3257±0.0357 ***
Compositions (low)	17	250	0.2855±0.0253	0.2835±0.0312	0.2669±0.0382
						Compositions (in)	18	500	0.3155±0.0452 **	0.2995±0.0267	0.3010±0.0286
Compositions (height)	16	1250	0.3162±0.0322 **	0.2958±0.0365	0.2869±0.0312 **
						Cerasus humilis Bunge extract	18	500	0.2921±0.0256	0.2898±0.0313	0.2858±0.0415
Chinese herbal medicine extract	17	500	0.2841±0.0276	0.2821±0.0425	0.2799±0.0358

Note: compare * P<0.05 with the model control group same period; * P<0.01; * * P<0.001.

From table 1 experimental result, the neck of femur of model control group rat and the bone density of femur distal end are starkly lower than Normal group, have significant difference (P<0.001), show osteoporosis model modeling success.What specific embodiment 2 was obtained has joint-improving all can increase the neck of femur of ovariectomized female rats and the BMD value of femur distal end significantly with the middle and high dosage group of the powder increasing bone substance density improving function, the femoral neck BMD value of the middle and high dosage group of the compositions (powder) of joint-improving and increase bone substance density improving function that what wherein specific embodiment 2 was obtained have, compared with same period model control group, has significant difference (P<0.01).The middle and high dosage component of neck of femur does not improve 16.94%, 17.2% than the bone density of model group; The middle and high dosage component of femur meta does not improve 9.51%, 8.15% than the bone density of model group; The middle and high dosage component of femur distal end does not improve 15.41%, 10% than the bone density of model group.The powder group that what specific embodiment 2 was obtained have increases bone substance density improving function all than not adding Cerasus humilis Bunge extract group, traditional water extraction alcohol extraction Chinese herbal medicine group effect is strong, also illustrate: Cerasus humilis Bunge extract of the present invention, Chinese herbal medicine extract have all made contribution to compositions, have certain advance simultaneously.

The powder that product effect obtained by embodiment of the present invention 3-8 is prepared than embodiment 2 is slightly poor, but it is more close, to sum up, the bone density increase of middle and high dosage group to ovariectomized female rats that what prepared by the present invention have increases the compositions of bone substance density improving function has good effect.

Table 2 have joint-improving and increase bone substance density improving function powder on ovariectomized in rats wet density, dry density affect result

Group	Femur volume (mL)	Femur dry weight (g)	Femur wet density (g/mL)	Femoral shaft density (g/mL)
					Model control group	0.54±0.02	0.5498±0.0524	1.51±0.07	1.07±0.05
Normal group	0.51±0.04**	0.5217±0.0427	1.63±0.12*	1.19±0.07***
					Compositions (low)	0.55±0.03	0.5386±0.0513	1.53±0.09*	1.04±0.07
Compositions (in)	0.54±0.03	0.5648±0.0412	1.58±0.09	1.16±0.06***
					Compositions (height)	0.53±0.04	0.5635±0.0522	1.55±0.12	1.14±0.05***
Cerasus humilis Bunge extract	0.53±0.02	0.5593±0.0263	1.54±0.12	1.13±0.04
					Chinese herbal medicine extract	0.53±0.03	0.5476±0.0412	1.53±0.10	1.11±0.03

Note: compare * P<0.05 with the model control group same period; * P<0.01; * * P<0.001.

From table 2 experimental result, femur wet density and the dry density value of model control group rat all obviously reduce, and compared with same period Normal group, have significant difference (P<0.05, P<0.001); The middle and high dosage group of powder that what specific embodiment 2 was obtained have joint-improving and increase bone substance density improving function can increase femur wet density and the dry density of ovariectomized female rats, the femoral shaft density value with the high dose group of the powder increasing bone substance density improving function that wherein specific embodiment 2 is obtained is compared with same period model control group, there is significant difference (P<0.001, P<0.01); In sum, in the powder that what specific embodiment 2 was obtained have joint-improving and increase bone substance density improving function, the bone density increase of dosage to ovariectomized female rats has good effect.The powder group that what specific embodiment 2 was obtained have joint-improving and increase bone substance density improving function all than not adding Cerasus humilis Bunge extract group, traditional water extraction alcohol extraction Chinese herbal medicine group effect is strong, also illustrate: Cerasus humilis Bunge extract of the present invention, Chinese herbal medicine extract have all made contribution to compositions, have certain advance simultaneously.

The powder that product effect obtained by embodiment of the present invention 3-8 is prepared than embodiment 2 is slightly poor, but it is more close, to sum up, the bone density increase of middle and high dosage group to ovariectomized female rats of what prepared by the present invention have joint-improving and the compositions that increases bone substance density improving function has good effect.

Two, clinical trial

The compositions (powder) with joint-improving and increase bone substance density improving function obtained to specific embodiment 2, choose the patient suffering from osteoporosis and verify, usage and dosage is: oral, 450mg/ bag, takes 30 days cycles by each 2 bags, one day twice, result was as shown in table 3.

Table 3 has the compositions of joint-improving and increase bone substance density improving function to osteoporosis symptoms patient clinical trial data

As can be seen from Table 3, there is untoward reaction in none example of 15 routine sufferers of osteoporosis face, after 30 days, symptom all alleviates.Illustrate that the compositions (powder) with joint-improving and increase bone substance density improving function that specific embodiment 2 obtains is good to the therapeutic effect of osteoporosis symptoms.

The compositions (powder) with joint-improving and increase bone substance density improving function that product effect obtained by embodiment of the present invention 3-8 is prepared than embodiment 2 is more close, to sum up, what prepared by the present invention have joint-improving and the compositions (powder) increasing bone substance density improving function have good therapeutic effect to the patient suffering from osteoporosis symptoms.

Claims (10)

1. the compositions that there is joint-improving and increase bone density, prepared by the raw material primarily of following parts by weight: calcium lactate 20-50 part, Chinese herbal medicine extract 12-30 part, Cerasus humilis Bunge extract 15-25 part, Glucosamine sulfate potassium chloride 5-15 part, chondroitin sulfate 5-10 part, milk calcium 2-10 part, Calcium peptide of casein 2.5-8 part, magnesium lactate 3-6 part, dimethyl sulfone 2-4 part, Semen Vitis viniferae extract 1.5-4 part, zinc lactate 0.15-0.3 part; Also comprise the adjuvant of following parts by weight: maltodextrin 5-20 part, D-mannital 5-20 part, modified dietary fiber 5-20 part, guar gum 2-10 part, hydroxypropyl emthylcellulose 0.5-1.5 part, citric acid 0.5-1.5 part, silicon dioxide 0.2-1 part, stevioside 0.01-0.15 part;

Described Chinese herbal medicine extract is prepared through ultrasonic cleaning, low temperature enzymolysis, water extraction alcohol extraction and microwave-assisted supersound extraction for raw material with Rhizoma Drynariae, Herba Epimedii, Fructus Lycii;

Described Cerasus humilis Bunge extract is with Chinese Cerasus humilis Bunge fresh fruit for raw material, adopts ultrasonic cleaning, microwave-assisted supersound extraction, high-pressure pulse electric to extract and prepare through natural fermentation.

2. have the compositions of joint-improving and increase bone density as claimed in claim 1, it is characterized in that, prepared by the raw material primarily of following parts by weight: calcium lactate 30-40 part, Chinese herbal medicine extract 15-25 part, Cerasus humilis Bunge extract 18-23 part, Glucosamine sulfate potassium chloride 8-12 part, chondroitin sulfate 7-9 part, milk calcium 5-8 part, Calcium peptide of casein 4-6 part, magnesium lactate 4-5.5 part, dimethyl sulfone 2.5-3.5 part, Semen Vitis viniferae extract 2-3.5 part, zinc lactate 0.18-0.25 part; Also comprise the adjuvant of following parts by weight: maltodextrin 10-18 part, D-mannital 8-15 part, modified dietary fiber 15-18 part, guar gum 4-6 part, hydroxypropyl emthylcellulose 0.8-1.2 part, citric acid 0.8-1.2 part, silicon dioxide 0.4-0.6 part, stevioside 0.06-0.12 part.

3. have the compositions of joint-improving and increase bone density as claimed in claim 1, it is characterized in that, the preparation method of described Chinese herbal medicine extract comprises the steps: to count by weight, takes Rhizoma Drynariae 5-12 part, Herba Epimedii 5-12 part, Fructus Lycii 3-8 part, put in the ultrasonic washing unit filling 0.1-0.3% sodium bicarbonate solution in 200W, 30KHz cleans 10-15min, drain, said herbal medicine being crushed to particle diameter is less than 2 millimeters, put Homogeneous phase mixing in container and add the water of 3-6 times of weight, obtain mixed material, control temperature 70 DEG C-90 DEG C keeps 2-4h, then 40-50 DEG C is cooled to, be 3.5-4.5 by lactic acid adjust ph, at power 150-300W, microwave extraction is carried out under frequency 2000Hz condition, wherein, each microwave exposure total time 60-80s, carry out compartment irradiation: irradiation 10s, interval 10s, irradiation like this 10 times, simultaneously at power 200-300W, ultrasonic assistant extraction is carried out under frequency 30-40KHz condition, then the mixing enzyme preparation adding mixed material gross weight 3-7% carries out enzymolysis, be 5.5-6.8 by lactic acid adjust ph, enzymolysis 2-4h, finally add the mixture of mixed material 0.5-3 times of w ethanol and propanol, the mass ratio of ethanol and propanol mixing is 1:1-3, control temperature to 60 DEG C-78 DEG C of maintenance 3-4h, filter, obtain the first filtrate, add the water of filtering residue 1-3 times of weight, control temperature 85 DEG C-95 DEG C keeps 1-3h, is then cooled to 25-35 DEG C, filters, obtains the second filtrate, first filtrate and the second filtrate are merged according to mass ratio 2-4:1-3, filter vacuum concentrates postlyophilization, pulverizes and obtains Chinese herbal medicine extract,

Described mixed enzyme is glucanase, xylanase, pentosanase, pectase 2-4:2-4:1-3:1-2 Homogeneous phase mixing in mass ratio.

4. there is the compositions of joint-improving and increase bone density as claimed in claim 1, it is characterized in that, the preparation method of described Cerasus humilis Bunge extract comprises the steps: Chinese Cerasus humilis Bunge fresh fruit to put in the ultrasonic washing unit filling 0.8-1.2% sodium bicarbonate solution in 200W, 30KHz cleans 10-15min, drain, pulverize immediately after-18--22 DEG C of freezing 1-2h, freezing thickness of feed layer 3-5cm, powder particle diameter 0.5-3mm, then add and pulverize raw materials quality 0.5-2 water doubly, be 3.0-3.5 by lactic acid adjust ph, at power 200-300W, microwave extraction is carried out under frequency 2000Hz condition, wherein, each microwave exposure total time 100-120s, carry out compartment irradiation: irradiation 10s, interval 10s, control temperature 20-35 DEG C, irradiation like this 10 times, simultaneously at power 200-300W, ultrasonic assistant extraction is carried out under frequency 30-40KHz condition, insulation 1-3h, then, microwave extraction is carried out under power 200-400W, frequency 2000Hz condition, wherein, each microwave exposure total time 120-135s, carry out compartment irradiation: irradiation 15s, interval 10s, control temperature 40-50 DEG C, irradiation like this 10 times, simultaneously at power 300-500W, carry out ultrasonic assistant extraction under frequency 40-50KHz condition, last Temperature fall to room temperature, in electric field intensity 15-25kV/cm, burst length 300-500 μ s, carries out high-pressure pulse electric and extracts 15-20min under pulse frequency 200-300Hz condition, abundant stirring extracting solution, sealing, natural fermentation 4-10d, filtering fermentation liquor obtains the first filtrate, add the water rinse of filtering residue 2 times, filter to obtain the second filtrate, by the first filtrate and the second filtrate 1:2-5 Homogeneous phase mixing in mass ratio, namely mixed liquor ultrafiltration and concentration, lyophilization, 30 DEG C of pulverize at low temperature obtain Cerasus humilis Bunge extract to particle diameter 0.1-0.3mm.

5. there is the compositions of joint-improving and increase bone density as claimed in claim 1, it is characterized in that, the preparation method of described modified dietary fiber comprises the following steps: by inulin, apple fiber, Herba avenae fatuae fiber, Semen Tritici aestivi fiber, Testa oryzae, wheat bran 8-10:4-7:3-5:2-4:1-3:1-2 Homogeneous phase mixing in mass ratio, add its quality 3-7 water doubly, room temperature 200-300W, 35-40KHz condition supersound extraction 10-15min, simultaneously in electric field intensity 20-40kV/cm, burst length 400-500 μ s, carries out high-pressure pulse electric extraction under pulse frequency 200-300Hz condition; Be 4.5-6.5 by lactic acid adjust ph, add the enzyme of mixture quality 0.1-0.3%, in 45-55 DEG C of enzymolysis 20-48min; Enzymolysis solution concentrating under reduced pressure, lyophilization, pulverize at low temperature to particle diameter are that namely 0.1-0.3mm obtains modified dietary fiber;

Described enzyme is xylanase, cellulase, laccase, pectase, tannase, amylase and protease 6-10:4-8:3-5:2-4:1-3:1-3:0.3-0.5 Homogeneous phase mixing in mass ratio.

6. have the compositions of joint-improving and increase bone density as claimed in claim 1, it is characterized in that, the dosage form of described compositions is oral formulations.

7. have the compositions of joint-improving and increase bone density as claimed in claim 6, it is characterized in that, described oral formulations is powder, capsule, tablet or granule.

8. there is as described in as arbitrary in claim 1-7 joint-improving and increase the preparation method of compositions of bone density, it is characterized in that, comprise the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 60-120 mesh sieve, then mix 8-25min, obtain mixed powder;

2) by maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, the stevioside aqueous solution making 13-18% soluble in water, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 10-20 mesh sieve, obtain wet granular, put in power 3000W, frequency 2000Hz, temperature 55-65 DEG C dry 3-8min in microwave dryer, with the quick granulate of 10-20 mesh sieve;

4) whole good granule and silicon dioxide mixing 5-10min, after mix homogeneously, make powder, capsule, tablet or granule.

9. have the preparation method of the compositions of joint-improving and increase bone density as claimed in claim 8, it is characterized in that, the preparation of described powder comprises the steps:

1) according to formula, extracting lactic acid calcium, Chinese herbal medicine extract, Cerasus humilis Bunge extract, Glucosamine sulfate potassium chloride, chondroitin sulfate, milk calcium, Calcium peptide of casein, magnesium lactate, dimethyl sulfone, Semen Vitis viniferae extract, zinc lactate respectively, pulverize, cross 100 mesh sieves, then mix 18min, obtain mixed powder;

2) by soluble in water to maltodextrin, D-mannital, modified dietary fiber, guar gum, hydroxypropyl emthylcellulose, citric acid, stevioside make 15% aqueous solution, as binding agent;

3) in described mixed powder, add described binding agent and make soft material, granulate with 16 mesh sieves, obtain wet granular, put in power 3000W, frequency 2000Hz, the dry 5min of temperature 60 C in microwave dryer, with the quick granulate of 16 mesh sieve;

4) whole good granule and silicon dioxide mixing 8min, after mix homogeneously, pulverizes, crosses 100 mesh sieves, subpackage, the obtained powder of sealing.

10. the compositions having joint-improving as described in as arbitrary in claim 1-7 and increase bone density is preparing the application in food, health product or medicine.