CN106072651A - A kind of have compositions increasing bone density, anti-inflammatory and analgesic effect and preparation method thereof - Google Patents

A kind of have compositions increasing bone density, anti-inflammatory and analgesic effect and preparation method thereof Download PDF

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CN106072651A
CN106072651A CN201610570478.7A CN201610570478A CN106072651A CN 106072651 A CN106072651 A CN 106072651A CN 201610570478 A CN201610570478 A CN 201610570478A CN 106072651 A CN106072651 A CN 106072651A
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parts
prescription
calcium carbonate
bone density
calcium
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CN106072651B (en
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吴世德
徐传彬
吴维群
贾美春
许敏
韩苗苗
谭倩
徐鑫
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SHANDONG MINGREN FURUIDA PHARMACEUTICAL Co Ltd
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SHANDONG MINGREN FURUIDA PHARMACEUTICAL Co Ltd
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health

Abstract

The present invention relates to a kind of compositions with increase bone density, anti-inflammatory and analgesic effect and preparation method thereof.A kind of have increase bone density, the compositions of anti-inflammatory and analgesic effect, and crude drug component is as follows: chondroitin sulfate, glucosamine hydrochloride, calcium carbonate, hyaluronate sodium, dimethyl sulfone, Radix Puerariae extract.Film coating tablet that the invention still further relates to utilize said composition to prepare and preparation method thereof.Compositions described in Ben all can play preferable curative effect in terms of increasing bone density；Each component has synergism, it is easier to promote the absorption of calcium, it is possible to preferably increase bone density；Proving through animal function test, this compositions can significantly improve dot density and femur distal end bone density in the femur weight of rat, calcium content of bone, femur.

Description

A kind of have compositions increasing bone density, anti-inflammatory and analgesic effect and preparation method thereof
Technical field
The present invention relates to a kind of compositions with increase bone density, anti-inflammatory and analgesic effect and preparation method thereof, belong to guarantor Health food technical field.
Background technology
Osteoporosis and osteoarthritis are middle-aged and elderly people common diseases, and patient groups occupies significant proportion in China, Become and affect the major issue that our people is healthy.The whole world there are about 200,000,000 patients with osteoporosis, and its sickness rate leaps to often See disease, the 7th of frequently-occurring disease, and annual average rate of increase is in the impetus quickly increased.Treatment to this disease clinically, how with oral Calcium preparation and vitamin D are main, and the absorption of calcium can slow down the loss of bone, improve bone mineralising, but clinical research shows, except Replenishing the calcium, patient also should carry out improving bone density, strengthening bone strength and the Comprehensive Treatment of prevention fracture simultaneously.In recent years, along with people Osteoporosis study of incident mechanism goed deep into, having increases bone density, prevents chondrocyte injury, promotes cartilage matrix Repair and reconstruction, improve the material of joint motion, anti-inflammatory and analgesic effect, because of the mechanism of action that it is unique, safe and reliable, increasingly Being favored by people, people are more likely to the product selecting pure natural, green, side effect little, effective.
Chondroitin sulfate is animal distribution in vivo most widely a kind of extracellular matrix glycosaminoglycan, mends mainly as meals Fill agent for Saving cortilage.Chondroitin sulfate is as the important component part of connective tissue, it is possible to bound water molecule is used for lubricating With support joint, make joint motion freely；Owing to significantly parent is cartilage, it can preferentially enter cartilaginous tissue, protects cartilage.Cause This, be mainly used in the treatment of osteoarthritis.It can also reach to repair cartilage, promote regenerating bone or cartilage by alleviating various symptoms.
Glucosamine hydrochloride is a kind of amino monosaccharide that chitin obtains through hydrochloric acid water solution.It is special that it is naturally occurring in human body It is not in articular cartilage, is the constituent of proteoglycan in the base substance of synthesizing amino polysaccharide and articular cartilage, as pass The supplementary of joint cartilage is widely used.Scientific investigations showed that, after 30 years old, with advancing age, D-glucosamine in human body Content is gradually lowered, and the abrasion of articular cartilage is constantly accumulated, so middle-aged and elderly people is susceptible to suffer from the diseases such as osteoarthritis.In American-European medical science Boundary, glucosamine hydrochloride is the most approved to the joint disease medicative nutrient and healthcare products of tool.
Hyaluronate sodium is to be widely present in people and the polymer substance of the various tissue of animal, is a kind of high viscosity material, There is extraordinary biocompatibility.Hyaluronate sodium, as the main component of knuckle synovia, gives the viscoelasticity that synovial fluid is good, To maintaining, joint normal physiological function is most important.There is electrolyte and moisture regulation, lubricating joint in participation extracellular fluid, resist The different physiological roles such as imperial infection, participation wound healing, the performance to protection, nutrition and the function in joint all plays important work With.
Calcium is the important minerals composition constituting animal skeleton tissue, and in body various physiology and biochemistry mistake Journey plays an important role.Bone mainly has calcium, phosphorus to be deposited in collagen stroma with the form of hydroxyapatite, a large amount of clinical practices and The research of Epidemiological study shows, calcium Deficiency of Intake is probably osteoporotic risk factor.Calcium carbonate is " vitamin, ore deposit Materials compounds list " in article, be regulation allow use calcium source.
Dimethyl sulfone (MSM) is a kind of organic sulfur compound, is the necessary material of human collagen albumen synthesis.Arthritic Cartilage sulfur content only has the 1/3 of normal human cartilage's sulfur content, supplementary cystine can increase arthritic's cartilage sulfur content, and warp The dimethyl sulfone test of isotope S35, it has been shown that sulfur in cystine, is that the sulfur from dimethyl sulfone obtains.Dimethyl sulfone can With analgesia, it can stop the propagation of pain nerve signal, it is also possible to improves collagen and connects, repairs injured tissue.Animal is real Verifying bright, dimethyl sulfone can contain kneed deterioration really, it is also possible to increases effect rather than the quantity of hydrocortisone.Skin Matter alcohol is the natural anti-inflammatory hormone in human body.Dimethyl sulfone can also suppress fibroblastic generation, and fibroblast It it is then the principal element causing edema.
Radix Puerariae is legume pueraria lobata or the dry root of Radix Puerariae rattan, and nature and flavor are sweet, pungent, cool, returns spleen, stomach warp, has expelling pathogenic factors from muscles and move back Heat, promote the production of body fluid, rash, effect of yang invigorating antidiarrheal.Modern pharmacology research proves that Radix Puerariae can expand coronary vasodilator, improves microcirculation, Reduce blood high viscosity and high coagulant state, have blood circulation invigorating efficacies, also improve arrhythmia, blood fat reducing, antioxidation, reduces blood glucose and relieves the effect of alcohol Function, Radix Puerariae low dose can significantly inhibit the decline of ovariectomized mouse bone density；The decline of suppression Distal femoral metaphysis bone amount Minimizing with bone trabecula width；Inhibit the increase of osteoclast number simultaneously.Wherein the Radix Puerariae of high dose is to bone density and bone amount Raising the most substantially exceed normal group, show that it has significant curative effect.
Increase bone density disclosed in prior art and the medicine of anti-inflammatory and analgesic effect, mainly by chondroitin sulfate, hydrochloric acid Glucosamine, calcium carbonate, hyaluronate sodium are made, although can improve osteoporosis, repairing articular cartilage to a certain extent, Alleviate osteoporosis and bone articular cartilage tissue injury or degeneration, but effect is the most notable, it is impossible to meet patient actual Demand.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, it is provided that a kind of have increase bone density, the compositions of anti-inflammatory and analgesic effect And preparation method thereof.
Technical solution of the present invention is as follows:
A kind of have increase bone density, the compositions of anti-inflammatory and analgesic effect, and crude drug component is as follows, is weight portion:
Chondroitin sulfate 10～60 parts, glucosamine hydrochloride 10～60 parts, calcium carbonate 10～50 parts, hyaluronate sodium 1 ～10 parts, dimethyl sulfone 1～10 parts, Radix Puerariae extract 1～20 parts.
According to currently preferred, in described Radix Puerariae extract, the mass percentage content of Radix Puerariae isoflavone is not less than 40%.
According to currently preferred, crude drug component is as follows, is weight portion:
Chondroitin sulfate 20～40 parts, glucosamine hydrochloride 20～40 parts, calcium carbonate 20～35 parts, hyaluronate sodium 2 ～5 parts, dimethyl sulfone 1～2 parts, Radix Puerariae extract 8～12 parts.
According to the present invention it is further preferred that crude drug component is as follows, it is weight portion:
Chondroitin sulfate 27 parts, glucosamine hydrochloride 27 parts, calcium carbonate 30 parts, hyaluronate sodium 4 parts, dimethyl sulfone 1 Part, Radix Puerariae extract 11 parts.
Above-mentioned have increase bone density, anti-inflammatory and analgesic effect compositions preparation have increase bone density, anti-inflammatory and antalgic Application in the health product of effect.
According to currently preferred, the dosage form of described health product is tablet, granule, capsule；It is further preferred that institute Stating tablet is film coating tablet, dispersible tablet, buccal tablets, chewable tablet.
The above-mentioned film coating tablet with the compositions increasing bone density, anti-inflammatory and analgesic effect, component is as follows, all attaches most importance to Amount part:
Crude drug 120～200 parts, filler 0.1～50 parts, disintegrating agent 0.1～2 parts, lubricant 0.1～2 parts, binding agent 1～3 part, film coating agent 3～5 parts.
According to currently preferred, described filler is microcrystalline Cellulose；
According to currently preferred, described disintegrating agent is polyvinylpolypyrrolidone (PVPP)；
According to currently preferred, described lubricant is magnesium stearate；
According to currently preferred, described binding agent is PVP K30；
According to currently preferred, described film coating agent is stomach dissolution type pharmaceutical films coating materials.
The preparation method of above-mentioned film coating tablet, step is as follows:
I Radix Puerariae extract is individually pelletized by (), cross 20 mesh sieves, granulate, prepare Radix Puerariae extract granule；
(ii) by mass percentage concentration 8～12% ratio film coating agent is dissolved in the second that volumetric concentration is 70% In alcoholic solution, prepare film coating liquid；
(iii) by hyaluronate sodium, dimethyl sulfone and filler, disintegrating agent, lubricant, binding agent by equal increments method Radix Puerariae extract granule prepared with chondroitin sulfate, glucosamine hydrochloride, calcium carbonate, step (i) after mix homogeneously mixes Uniformly, use wet granulation, tabletting, use the film coating liquid coating that step (ii) is prepared, to obtain final product.
The steps such as above-mentioned granulation, equal increments method, wet granulation, tabletting, coating are the conventional steps of this area, relevant Condition step is all by prior art operation.
The main pharmacodynamics of each crude drug of the present invention is as follows:
1, chondroitin sulfate
Pharmacological effect and clinical studies show, this product has the effect that (1) lubricates and supports joint effect；(2) protection Cartilaginous tissue；(3) repair cartilage, promote regenerating bone or cartilage.Therefore, on the one hand chondroitin sulfate can reach to control by protection cartilage Treat the effect of osteoarthritis, on the other hand can also reach to repair cartilage, promote regenerating bone or cartilage by alleviating various symptoms.Sulphuric acid Chrondroitin, as health product, is applied through for many years, it was demonstrated that chondroitin sulfate is to improving Senile degenerative arthritis, rheumatism joint Scorching effect is notable；
2, glucosamine hydrochloride
Pharmacological effect and clinical studies show, this product has the effect that (1) lubricating joint, protection cartilaginous tissue；(2) Alleviate arthralgia, suppress and the joint degeneration that disappears is formed；(3) calcium absorption, pre-preventing bone rarefaction are promoted.Therefore, aminoguanidine hydrochloride Glucose can be not only used for treating and preventing the osteoarthritis in the various joint of whole body, it is also possible to by promoting that the absorption of calcium rises To preventing osteoporotic effect；
3, hyaluronate sodium
Pharmacological effect and clinical studies show, this product has the effect that (1) is to articular cavity lubrication and buffering stress；(2) Reduce intraarticular sepage；(3) cartilage of damage is repaired.Therefore, hyaluronate sodium is a kind of safety for the treatment of osteoarthritis, reason Think, effective medicine, osteoarthritis can be played good therapeutical effect.
4, calcium carbonate
Although calcium is to increase the main component of bone density, but the absorption of calcium is affected by many factors, so majority of populations The situation of " easily mending difficulty to receive " often occurs when daily replenishing the calcium.It was found that age factor is maximum on the impact of calcium absorption, it is in life The absorbability of long budding Children and teenager people's calcium is strong, and the age increases, and the absorbance of calcium just declines.Infant may be up to 50～60%, children and youth 30～40%, adult 20～30%, middle age 10～20%, within more than 60 years old, are less than 10%.Institute With, mid-aged population is easiest to osteoporosis occur, more should focus on the absorption of calcium while supplement calcium.
5, dimethyl sulfone
Arthritis is mainly degeneration and the Secondary cases hyperosteogeny of articular cartilage.Mucus due to junction, joint Film is formed by containing sulfoprotein and glucamine etc..The protein of sulfur-bearing is mainly made up of the cystine of sulfur-bearing, and Guang ammonia Element sulphur in acid is mainly derived from dimethyl sulfone.The Protocollagen of sulfur-bearing and glucamine etc., have and promote collagen protein Producing, increase the combination of water, help to repair the function of damaged cartilage, injured cartilage can be made to recover normal, periosteum liquid is richer, more has Viscosity, thus strengthen the defencive function of periosteum, alleviate osteoarticular friction, reduce misery.Additionally, arthritic takes analgesia Medicine, often causes the side effect such as flatulence, headache, but as added dimethyl sulfone in the diet, can overcome this side effect.
6, Radix Puerariae extract
The medicine-food two-purpose resource that Radix Puerariae is announced as Ministry of Public Health, has increase bone density, improves primary osteoporosis Shape, improve cerebral blood circulation, reducing blood sugar and blood lipid, the effect of relieving the effect of alcohol etc..Isoflavone like substance contained in Radix Puerariae can regulate bone generation Thank, promoting bone growing, improve osseous tissue interior hardness, increase bone density；It is complete that Radix Puerariae isoflavone can significantly improve ovariectomized female rats Body bone mineral content (BMC) and Whole Body Bone Scanning mineral density (BMD), can improve femur relative mass volume, even recover bone ash calcium salt close Degree is to sham operated rats (normally) level；Bone biomechanical index can be significantly improved, improve femur and the peak load of tibia and knot Structure intensity；The research of ovariectomized female rats tibia trace element effect is shown by Radix Puerariae isoflavone, and Radix Puerariae isoflavone can improve tibia Zinc, magnesium, manganese, copper, the content of chromium, the trace element improving castrated rats loses situation.Radix Puerariae total flavones has also been proved improvement The effect of the bone density of castrated rats, calcium content of bone and bone weight；Puerarin can suppress the high transition status of ovariectomized in rats, Increasing tibia mineral quality and inorganic element content, prompting puerarin can be effectively improved bone metabolism, the sclerotin to ovariectomized female rats Loose have preventive and therapeutic effect.Puerarin can promote osteoblastic proliferation, moreover it is possible to strengthens alkaline phosphatase activities, promote Mineral nodules Formed, show that it also has facilitation to osteoblast differentiation.Puerarin may be by promoting that osteoblastic proliferation and differentiation come Promoting bone growing Radix Puerariae can reduce the bone turnover rate of patients with osteoporosis, suppresses bone resorption.
Beneficial effect
1, the present invention is first by chondroitin sulfate, glucosamine hydrochloride, hyaluronate sodium, calcium carbonate, dimethyl sulfone, Pueraria lobota Six kinds of compositions of root extract carry out compatibility, and preparation has increase bone density, the compositions of anti-inflammatory and analgesic effect；Increasing bone density Aspect can play preferable curative effect；Each component has synergism, it is easier to promote the absorption of calcium, it is possible to preferably increase bone close Degree；Proving through animal function test, this compositions can significantly improve dot density in the femur weight of rat, calcium content of bone, femur With femur distal end bone density；According to " health food inspection and assessment technique specification (version in 2003) " criterion, show this Invention combination has the function increasing bone density；
2, of the present invention have in the compositions increasing bone density, anti-inflammatory and analgesic effect, and the present invention uses chondroitin sulfate Element with glucosamine hydrochloride with the use of, experiments verify that, the two coordinate after combine other active ingredient use, only have Bitterly, promote effect of regenerating bone or cartilage, different times cartilage injury is all had certain protection and therapeutical effect, can preferably prolong The progress of slow osteoarthritis；Hyaluronate sodium and glucosamine hydrochloride with the use of, there is the function improving joint；Hyalomitome Acid and chondroitin sulfate with the use of, can obviously relieve the clinical symptoms of Human Osteoarthritis；Calcium carbonate is joined with Radix Puerariae extract Close and use, there is the bone metabolism improving Osteoporosis, increase the function of bone density, effectively improve sclerotin and dredge The pathology disease of pine；Dimethyl sulfone and chondroitin sulfate with the use of, the formation of cartilage can be strengthened, effective subjoint is scorching Treatment；
3, of the present invention have increase bone density, anti-inflammatory and analgesic effect compositions safe and effective, toxicological test proves, Respectively with 25 times of human body recommended amounts every day, 50 times, 100 times of present compositions give rat through gavage, continuous 30 days, each dose Amount treated animal body weight increases, food-intake and food utilization there are no significant compared with negative control medicine group difference (P ＞ 0.05), Hematological indices, blood biochemistry index, internal organs absolute weight and dirty/body ratio compared with negative control group without significant difference (P ＞ 0.05), histopathologic examination, the present composition damages without obvious by inspection internal organs；
4, of the present invention have increase bone density, anti-inflammatory and analgesic effect compositions at chondroitin sulfate, aminoguanidine hydrochloride On the basis of glucose and calcium preparation, increase and strengthen cartilage, lubricating joint, alleviate arthralgia, the activity of increase bone substance density improving function Composition, is main active component with chondroitin sulfate, calcium carbonate, with hyaluronate sodium, glucosamine hydrochloride, dimethyl sulfone, Pueraria lobota Root extract combines, and osteoarthrosis health care is had good synergism, several all has health-care effect to osteoarthrosis by above-mentioned Active component carries out compound recipe combination and makes preparation, meets health care requirement, and raw material side effect is little, effective, has wide market Prospect.
Detailed description of the invention
Below in conjunction with embodiment, technical scheme is further elaborated, but institute of the present invention protection domain does not limits In this.
Raw material sources
Chondroitin sulfate Shandong Hai Yu Bioisystech Co., Ltd is on sale.
Glucosamine hydrochloride Jinan Haidebei Marine Organism Engineering Co., Ltd. is on sale.
Hui Kang source, calcium carbonate Beijing bio tech ltd is on sale.
Bai Chuan bio tech ltd, Radix Puerariae extract Xi'an is on sale, after testing, and Radix Puerariae isoflavone in Radix Puerariae extract Mass percentage content >=40% of content.
Hyaluronate sodium Furuida Biochemical Co., Ltd., Shandong is on sale.
Li Nuo bio tech ltd, dimethyl sulfone Zhengzhou is on sale.
Microcrystalline Cellulose Beijing Feng Lijingqiu commerce and trade Co., Ltd is on sale.
Polyvinylpolypyrrolidone Beijing Feng Lijingqiu commerce and trade Co., Ltd is on sale.
Magnesium stearate Beijing Feng Lijingqiu commerce and trade Co., Ltd is on sale.
PVP K30 Beijing Feng Lijingqiu commerce and trade Co., Ltd is on sale.
Stomach dissolution type pharmaceutical films coating materials Beijing Feng Lijingqiu commerce and trade Co., Ltd is on sale.
Single component calcium carbonate increases the Evaluation of Functional experiment of bone density
Calcium is the important minerals composition constituting animal skeleton tissue, and calcium carbonate is " vitamin, mineral cpd name Material in singly ", is the calcium source of regulation permission use.For showing that calcium carbonate increases the effectiveness of bone density, calcium carbonate is carried out Following correlation test.
1 material and method
1.1 laboratory animals and environment: Wistar male rat, body weight about 60～75 grams.Experimental situation temperature 22 DEG C ± 2 DEG C, relative humidity 50% ± 10%.
1.2 dosage arrange and give mode with tested
Low calcio plinth feed formula such as table 1 below:
Table 1 low calcio plinth feed formula (Ca2+Meter, 150mg/100g)
Composition % Composition %
Casein 10.0 Salt-mixture 2.5
Analysis for soybean powder 15.0 Mixed vitamin 1.0
Semen Tritici aestivi flour 54.0 Choline chloride 0.3
Semen Maydis oil or Oleum Arachidis hypogaeae semen 4.0 Dl-methionine 0.2
Cellulose 2.0 Starch 11.0
Dosage is arranged: specify effective dose and the safe dose of calcium in " vitamin, the kind of mineral and consumption " Between 250mg-1000mg/ days, dosage safety is effective.Therefore, 4 calcium carbonate dosage group such as table 2 below it are provided with in test.
The different calcium carbonate dosage group of table 2
Group Calcium carbonate consumption every day (mg) Actual calcium content (mg)
Calcium carbonate 1 group 625 250
Calcium carbonate 2 groups 1250 500
Calcium carbonate 3 groups 1875 750
Calcium carbonate 4 groups 2500 1000
All feed low calcium normal feedstuff, drink deionized water for tested each group.It is tested that per os gavage once a day gives rat, fills Stomach volume is based on 1ml/100g.bw.Low calcium matched group replaces tested material solution gavage with isopyknic deionized water.Give continuously After 3 months, test increases the indices of bone substance density improving function.
1.3 key instruments: NORLAND STRATEC type Dual-energy X-rays absorptionmetry.
1.4 experimental technique
1.4.1 body weight determination: after fasting 12 hours, measures body weight.Measure the weight of animals once weekly.
1.4.2 femur gravimetry: animal feeding was put to death after 3 months, separates right side femur, roasting in 105 DEG C of baking boxs To constant weight, weigh backbone's weight.
1.4.3 calcium content of bone and Calcium Content in Foodstuff measure: low calcio plinth Feed Sample, through uniformly mixing, dries in an oven Dry, put exsiccator cooling, take out and grind.Take femur on the right side of rat to dry to constant weight at 105 DEG C, weigh backbone's weight, then pulverize, Grind.With calcium content in EDTA titration measuring low calcium normal feedstuff and thighbone samples.Low calcio plinth Calcium Content in Foodstuff is 146.0mg/100g, meet requirement of experiment.
1.4.4 femoral bmd measures: produces NORLAND STRATEC type Dual-energy X-rays absorptionmetry with the U.S. and measures femur Midpoint and the bone density of femur distal end.
1.5 experimental data statistics: use SPSS statistical software to carry out the one factor analysis of variance of each experimental group and matched group And compare between group.
2 experimental results
2.1 impacts on rat body weight
The original body mass of table 3 experimental rat
Group Number of animals (only) Body weight (g) P value
Low calcium matched group 9 70.51±4.40
Calcium carbonate 1 group 9 68.19±6.48 P ＞ 0.05
Calcium carbonate 2 groups 9 68.62±4.92 P ＞ 0.05
Calcium carbonate 3 groups 9 69.99±5.59 P ＞ 0.05
Calcium carbonate 4 groups 9 68.44±4.81 P ＞ 0.05
Table 3 is visible, compares with low calcium matched group, each treated animal weight differences not statistically significant (P ＞ 0.05).
Body weight during table 4 experimental rat the 4th week
Table 4 is visible, compares with low calcium matched group, each treated animal weight differences not statistically significant (P ＞ 0.05).
Body weight during table 5 experimental rat the 8th week
Group Number of animals (only) Body weight (g) P value
Low calcium matched group 9 200.10±13.62
Calcium carbonate 1 group 9 204.68±17.00 P ＞ 0.05
Calcium carbonate 2 groups 9 200.59±20.81 P ＞ 0.05
Calcium carbonate 3 groups 9 205.00±22.86 P ＞ 0.05
Calcium carbonate 4 groups 9 214.31±17.60 P ＞ 0.05
Table 5 is visible, compares with low calcium matched group, each treated animal weight differences not statistically significant (P ＞ 0.05).
Table 6 experimental rat opisthosoma at end weight
Group Number of animals (only) Body weight (g) P value
Low calcium matched group 9 231.92±11.41
Calcium carbonate 1 group 9 233.06±18.51 P ＞ 0.05
Calcium carbonate 2 groups 9 232.30±19.75 P ＞ 0.05
Calcium carbonate 3 groups 9 238.62±20.17 P ＞ 0.05
Calcium carbonate 4 groups 9 243.81±18.48 P ＞ 0.05
Table 6 is visible, compares with low calcium matched group, each treated animal weight differences not statistically significant (P ＞ 0.05).
2.2 femur weight
Table 7 each treated animal femur weight
Group Number of animals (only) Femur weight (g) P value
Low calcium matched group 9 0.3384±0.0420
Calcium carbonate 1 group 9 0.3874±0.0747 P ＞ 0.05
Calcium carbonate 2 groups 9 0.4084±0.0403 P ＜ 0.05
Calcium carbonate 3 groups 9 0.4151±0.0530 P ＜ 0.05
Calcium carbonate 4 groups 9 0.4184±0.0352 P ＜ 0.05
Compare with low calcium matched group*P ＜ 0.05
From table 7, compared with low calcium matched group, 2,3,4 groups of the most statistically significant (P of femur weight differential of calcium carbonate ＜ 0.05).4 kinds of calcium carbonate dosage group femur weight relatively low calcium matched groups all present increase trend, 1 group of relatively low calcium comparison of calcium carbonate It is obvious that group, calcium carbonate 2 groups relatively calcium carbonate 1 group increases trend, and it is inconspicuous to increase trend between calcium carbonate 2,3,4 groups.
2.3 calcium content of bone
Table 8 each treated animal femur calcium content
Group Number of animals (only) Bone calcium weight (mg/g) P value
Low calcium matched group 9 207.77±13.48
Calcium carbonate 1 group 9 213.66±12.84 P ＞ 0.05
Calcium carbonate 2 groups 9 219.99±11.89<sup>*</sup> P ＜ 0.05
Calcium carbonate 3 groups 9 220.41±12.61<sup>*</sup> P ＜ 0.05
Calcium carbonate 4 groups 9 220.92±14.42<sup>*</sup> P ＜ 0.05
Compare with low calcium matched group*P ＜ 0.05
From table 8, compared with low calcium matched group, 2,3,4 groups of the most statistically significant (P of calcium content of bone difference of calcium carbonate ＜ 0.05).4 kinds of calcium carbonate dosage group calcium content of bone relatively low calcium matched groups all present increase trend, 1 group of relatively low calcium comparison of calcium carbonate It is obvious that group, calcium carbonate 2 groups relatively calcium carbonate 1 group increases trend, and it is inconspicuous to increase trend between calcium carbonate 2,3,4 groups.
2.4 femoral bmd
Table 9 each treated animal femur midpoint bone density
Group Number of animals (only) Midpoint bone density (g/cm<sup>2</sup>) P value
Low calcium matched group 9 0.0922±0.0163
Calcium carbonate 1 group 9 0.0951±0.0130 P ＞ 0.05
Calcium carbonate 2 groups 9 0.1153±0.0161<sup>*</sup> P ＜ 0.05
Calcium carbonate 3 groups 9 0.1169±0.0132<sup>*</sup> P ＜ 0.05
Calcium carbonate 4 groups 9 0.1198±0.0143<sup>*</sup> P ＜ 0.05
Compare with low calcium matched group*P ＜ 0.05
From table 9, compared with low calcium matched group, 2,3,4 groups of femur midpoint bone density differences of calcium carbonate all have statistics Meaning (P ＜ 0.05).4 kinds of calcium carbonate dosage group femur midpoint bone density relatively low calcium matched groups all present increase trend, calcium carbonate 1 Organize relatively low calcium matched group, calcium carbonate 2 groups relatively calcium carbonate 1 group and increase trend substantially, and increase trend not between calcium carbonate 2,3,4 groups Substantially.
Table 10 each treated animal femur distal end bone density
Compare with low calcium matched group*P ＜ 0.05
From table 10, compared with low calcium matched group, 2,3,4 groups of femur distal end bone density differences of calcium carbonate all have statistics Learn meaning (P ＜ 0.05).4 kinds of calcium carbonate dosage group femur distal end bone density relatively low calcium matched groups all present increase trend, carbon It is obvious that the acid relatively low calcium matched group of calcium 1 group, calcium carbonate 2 groups relatively calcium carbonate 1 group increases trend, and increases between calcium carbonate 2,3,4 groups Trend is inconspicuous.
3 brief summaries
The 4 groups of calcium carbonate dosage groups arranged according to effective dose and the safe dose of legal calcium, compared with low calcium matched group, All can improve dot density and femur distal end bone density in the femur weight of rat, calcium content of bone, femur, and present increase and become Gesture, 2,3,4 groups of femur weight differentials of calcium carbonate the most statistically significant (P ＜ 0.05).The relatively low calcium matched group of calcium carbonate 1 group, carbon It is obvious that acid calcium 2 groups relatively calcium carbonate 1 group increases trend, and it is inconspicuous to increase trend between calcium carbonate 2,3,4 groups.This experiment shows, The calcium of daily ingestion of doses, can increase bone density, pre-preventing bone rarefaction, when every day calcium dose increase to a certain amount of After, its bone density the most substantially increases.
Embodiment 1, the Evaluation of Functional of increase bone density
Chondroitin sulfate, glucosamine hydrochloride, hyaluronate sodium, calcium carbonate, dimethyl sulfone, Radix Puerariae extract six kinds one-tenth Dividing the compositions that different ratio is made, its action effect increasing bone density has different.For showing the increase bone of the present invention The effectiveness of density, the prescription investigating different ratio increases the action effect of bone density, the present invention has been carried out following dependency Test.
The present embodiment experimentally with above-mentioned " single component calcium carbonate increase bone density Evaluation of Functional experiment " Method is identical, low calcium matched group formula and the low calcium pair in " single component calcium carbonate increases the Evaluation of Functional of bone density and tests " Consistent according to group of formula, calcium carbonate group of formula and the carbonic acid in " single component calcium carbonate increases the Evaluation of Functional of bone density and tests " Calcium 1 group of formula is consistent.
The embodiment of the present invention arranges following prescription and contrast, refers to table 11:
Table 11 different ratio prescription and contrast
Chondroitin sulfate Glucosamine hydrochloride Radix Puerariae extract Calcium carbonate Hyaluronic acid Dimethyl sulfone
Contrast 1 5.4% 48.6% 10.9% 30.1% 3.7% 1.3%
Prescription 1 16.2% 37.8% 10.9% 30.1% 3.7% 1.3%
Prescription 2 27% 27% 10.9% 30.1% 3.7% 1.3%
Prescription 3 37.8% 16.2% 10.9% 30.1% 3.7% 1.3%
Contrast 2 48.6% 5.4% 10.9% 30.1% 3.7% 1.3%
Prescription 4 29.7% 29.8% 5.4% 30.1% 3.7% 1.3%
Prescription 5 34.5% 34.6% 10.9% 15% 3.7% 1.3%
Prescription 6 27.9% 27.9% 10.9% 30.1% 1.9% 1.3%
Prescription 7 27.3% 27.3% 10.9% 30.1% 3.7% 0.7%
Contrast 3 32.5% 32.4% 0 30.1% 3.7% 1.3%
Contrast 4 27.7% 27.6% 10.9% 30.1% 3.7% 0
Experimental result is as follows:
1, the impact on rat body weight
The original body mass of table 12 experimental rat
Group Number of animals (only) Body weight (g) P value
Low calcium matched group 9 68.03±4.35
Calcium carbonate group 9 68.29±5.47 P ＞ 0.05
Prescription 1 9 68.53±4.63 P ＞ 0.05
Prescription 2 9 69.62±5.32 P ＞ 0.05
Prescription 3 9 68.86±5.88 P ＞ 0.05
Prescription 4 9 68.67±6.78 P ＞ 0.05
Prescription 5 9 69.36±6.35 P ＞ 0.05
Prescription 6 9 68.37±6.21 P ＞ 0.05
Prescription 7 9 69.34±6.11 P ＞ 0.05
Contrast 1 9 68.06±6.42 P ＞ 0.05
Contrast 2 9 69.43±4.22 P ＞ 0.05
Contrast 3 9 69.69±5.12 P ＞ 0.05
Contrast 4 9 69.34±6.56 P ＞ 0.05
Table 12 is visible, compares with low calcium matched group, each treated animal weight differences not statistically significant (P ＞ 0.05).
Body weight during table 13 experimental rat the 4th week
Group Number of animals (only) Body weight (g) P value
Low calcium matched group 9 163.87±17.16
Calcium carbonate group 9 165.05±14.36 P ＞ 0.05
Prescription 1 9 164.36±15.38 P ＞ 0.05
Prescription 2 9 166.44±16.58 P ＞ 0.05
Prescription 3 9 165.27±18.21 P ＞ 0.05
Prescription 4 9 164.25±15.31 P ＞ 0.05
Prescription 5 9 167.33±14.28 P ＞ 0.05
Prescription 6 9 165.73±11.20 P ＞ 0.05
Prescription 7 9 162.24±14.32 P ＞ 0.05
Contrast 1 9 164.55±13.54 P ＞ 0.05
Contrast 2 9 165.35±14.22 P ＞ 0.05
Contrast 3 9 167.64±11.03 P ＞ 0.05
Contrast 4 9 166.32±16.34 P ＞ 0.05
Table 13 is visible, compares with low calcium matched group, each treated animal weight differences not statistically significant (P ＞ 0.05).
Body weight during table 14 experimental rat the 8th week
Table 14 is visible, compares with low calcium matched group, each treated animal weight differences not statistically significant (P ＞ 0.05).
Table 15 experimental rat opisthosoma at end weight
Group Number of animals (only) Body weight (g) P value
Low calcium matched group 9 234.36±14.25
Calcium carbonate group 9 234.05±17.18 P ＞ 0.05
Prescription 1 9 236.16±14.13 P ＞ 0.05
Prescription 2 9 235.74±16.34 P ＞ 0.05
Prescription 3 9 234.71±11.10 P ＞ 0.05
Prescription 4 9 235.31±13.27 P ＞ 0.05
Prescription 5 9 236.40±16.71 P ＞ 0.05
Prescription 6 9 237.35±16.21 P ＞ 0.05
Prescription 7 9 231.48±21.02 P ＞ 0.05
Contrast 1 9 238.67±16.32 P ＞ 0.05
Contrast 2 9 234.58±14.22 P ＞ 0.05
Contrast 3 9 236.65±13.58 P ＞ 0.05
Contrast 4 9 233.37±17.31 P ＞ 0.05
From table 15, compare with low calcium matched group, each treated animal weight differences not statistically significant (P ＞ 0.05).2、 Femur weight
Table 16 each treated animal femur weight
Compare with low calcium matched group*P ＜ 0.05,**P ＜ 0.01
From table 16, compared with low calcium matched group, prescription 1, prescription 2, prescription 3, prescription 4, prescription 5, prescription 6, prescription 7, contrast 1, contrast 2, contrast 3, contrast 4 and the most statistically significant (P ＜ 0.01, the P ＜ of calcium carbonate group femur weight differential 0.05).Prescription 1, prescription 2, prescription 3, prescription 4, prescription 5, prescription 6, prescription 7, contrast 1, contrast 2, contrast 3, contrast 4 femur weights Measuring relatively carbonic acid acid calcium group the most substantially to increase, wherein prescription 2 femur weight relatively other prescriptions increase degree becomes apparent from.
3, calcium content of bone
Table 17 each treated animal femur calcium content
Group Number of animals (only) Stock calcium weight (mg/g) P value
Low calcium matched group 9 209.77±12.69
Calcium carbonate group 9 220.99±11.79<sup>*</sup> P ＜ 0.05
Prescription 1 9 228.39±12.41<sup>**</sup> P ＜ 0.01
Prescription 2 9 234.46±15.38<sup>**</sup> P ＜ 0.01
Prescription 3 9 229.49±14.73<sup>**</sup> P ＜ 0.01
Prescription 4 9 228.69±13.64<sup>**</sup> P ＜ 0.01
Prescription 5 9 227.77±12.74<sup>**</sup> P ＜ 0.01
Prescription 6 9 227.86±15.38<sup>**</sup> P ＜ 0.01
Prescription 7 9 228.68±17.16<sup>**</sup> P ＜ 0.01
Contrast 1 9 228.46±12.41<sup>**</sup> P ＜ 0.01
Contrast 2 9 227.21±16.18<sup>**</sup> P ＜ 0.01
Contrast 3 9 226.75±13.55<sup>**</sup> P ＜ 0.01
Contrast 4 9 226.36±16.47<sup>**</sup> P ＜ 0.01
Compare with low calcium matched group*P ＜ 0.05,**P ＜ 0.01
From table 17, compared with low calcium matched group, prescription 1, prescription 2, prescription 3, prescription 4, prescription 5, prescription 6, prescription 7, contrast 1, contrast 2, contrast 3, contrast 4 and the most statistically significant (P ＜ 0.01, the P ＜ of calcium carbonate group calcium content of bone difference 0.05).Prescription 1, prescription 2, prescription 3, prescription 4, prescription 5, prescription 6, prescription 7, contrast 1, contrast 2, contrast 3, contrast 4 bone calcium and contain Measuring relatively carbonic acid acid calcium group the most substantially to increase, wherein prescription 2 calcium content of bone relatively other prescriptions increase degree becomes apparent from.
4, femoral bmd
Table 18 each treated animal femur midpoint bone density
Group Number of animals (only) Midpoint bone density (g/cm<sup>2</sup>) P value
Low calcium matched group 9 0.0919±0.0170
Calcium carbonate group 9 0.1187±0.0164<sup>*</sup> P ＜ 0.05
Prescription 1 9 0.1308±0.0198<sup>**</sup> P ＜ 0.01
Prescription 2 9 0.1531±0.0135<sup>**</sup> P ＜ 0.01
Prescription 3 9 0.1298±0.0213<sup>**</sup> P ＜ 0.01
Prescription 4 9 0.1201±0.0175<sup>**</sup> P ＜ 0.01
Prescription 5 9 0.1223±0.0239<sup>**</sup> P ＜ 0.01
Prescription 6 9 0.1332±0.0173<sup>**</sup> P ＜ 0.01
Prescription 7 9 0.1341±0.0138<sup>**</sup> P ＜ 0.01
Contrast 1 9 0.1261±0.0152<sup>**</sup> P ＜ 0.01
Contrast 2 9 0.1276±0.0213<sup>**</sup> P ＜ 0.01
Contrast 3 9 0.1268±0.0157<sup>**</sup> P ＜ 0.01
Contrast 4 9 0.1275±0.0181<sup>**</sup> P ＜ 0.01
Compare with low calcium matched group*P ＜ 0.05,**P ＜ 0.01
From table 18, compared with low calcium matched group, prescription 1, prescription 2, prescription 3, prescription 4, prescription 5, prescription 6, prescription 7, contrast 1, contrast 2, contrast 3, contrast 4 and calcium carbonate group femur midpoint the most statistically significant (the P ＜ 0.01, P of bone density difference ＜ 0.05).Prescription 1, prescription 2, prescription 3, prescription 4, prescription 5, prescription 6, prescription 7, contrast 1, contrast 2, contrast 3, contrast 4 femurs Bone density relatively carbonic acid acid calcium group in midpoint the most substantially increases, and wherein bone density relatively other prescriptions in prescription 2 femur midpoint increase degree more For substantially.
Table 19 each treated animal femur distal end bone density
Compare with low calcium matched group*P ＜ 0.05,**P ＜ 0.01
From table 19, compared with low calcium matched group, prescription 1, prescription 2, prescription 3, prescription 4, prescription 5, prescription 6, prescription 7, contrast 1, contrast 2, contrast 3, contrast 4 and calcium carbonate group femur the most statistically significant (the P ＜ of distal end bone density difference 0.01, P ＜ 0.05).Prescription 1, prescription 2, prescription 3, prescription 4, prescription 5, prescription 6, prescription 7, contrast 1, contrast 2, contrast 3, right The most substantially increase than 4 femur distal end bone density relatively carbonic acid acid calcium groups, wherein prescription 2 femur distal end bone density relatively other prescriptions Increase degree becomes apparent from.
5, brief summary
From experimental data it can be seen that (1) present composition (prescription) and calcium carbonate group, low calcium matched group, contrast phase Ratio, all can improve dot density and femur distal end bone density in the femur weight of rat, calcium content of bone, femur, all have statistics Meaning (P ＜ 0.01, P ＜ 0.05)；(2) present composition increase bone density effect is substantially better than calcium carbonate group；(3) prescription 1, Prescription 2, the composition proportion consumption combination of prescription 3, resulting composition is for animal femur midpoint and the bone density of femur distal end There is more significantly increasing action, hence it is evident that being better than contrasting 1 and contrasting 2, especially prescription 2 acts on best, and six kinds of compositions can reach To synergy.
Embodiment 2, the Evaluation of Functional of osteoarthritis treatment effect
1 material and method
1.1 animals: SD rat, cleaning grade, 150～180g, male and female half and half, 96.
1.2 test group arrange and tested give mode
1.2.1 sample preparation and test packet
It is standby that all given the test agent are all made into homogenous suspension with 0.3% xanthan gum grinding, and given the test agent is with prescription 1, group The tablet that side 2, prescription 3, contrast 1 are made is as test specimen (proportioning arranges and is shown in Table 20).
Table 20 present composition different ratio is arranged
96 rats buy raising 1 week, after measuring body weight, are randomly divided into following 6 groups, often 16 rats of group: (1) matched group (0.3% xanthan gum)；(2) model group (0.3% xanthan gum)；(3) prescription 1；(4) prescription 2；(5) prescription 3；(6) contrast 1.
1.2.2 giving mode: gastric infusion, 1ml/100g body weight, every morning is administered once, Per-Hop behavior 7 days.
2 test methods
The foundation of 2.1 osteoarthritis
By 4% papain (physiological saline solution) and 0.3mol/L cysteine solution (physiological saline solution) volume Mix than 1: 1 after setting to 0 .5h, mixed liquor 100 μ l was injected in Rat Right knee joint cavity in the 1st, 3,7 days in modeling respectively, matched group Inject normal saline with method, normally raise after modeling.Each group rat successive administration 3 weeks, overnight fasting after art time administration, place Dead 1/2 (each 4 of male and female) carry out following Indexs measure.
2.2 Testing index
Each group rat successive administration 3 weeks, overnight fasting after art time administration, put to death 1/2 (each 4 of male and female) respectively and carry out joint Gross examination of skeletal muscle, biochemical measurement, the detection of histopathological examination index.
2.3 data process and statistical method
Each group data, all to represent, compare employing t inspection and investigate significance, using P ＜ 0.05 as significant indexes between group.
3 results
3.1 joint gross findings
After modeling 3 weeks, compared with matched group, model group knee joint occurs sliding without obvious arthroedema, major part animal Film swelling, thickening, color burn, facies artieularis malleolaris in femur, cartilage layers thickness declines, and has no that articular surface is rotten to the corn, cartilage seriously lacks Damage, articular surface ulcer, cartilage such as strip off at the serious change；3 present composition treated animal generally speaking synovium of joint and The changing condition of cartilage is similar to model group, but the order of severity has certain alleviating；1 present composition contrast groups animal is whole For body, synovium of joint is similar to model group with the changing condition of cartilage, and the order of severity has certain alleviating, but with 3 prescription groups Compare the most more serious, be shown in Table 21.
Table 21 on the impact of rat bone arthritis model joint general form (n=8,)
Group Substantially mark in joint
Matched group 0±0
Model group 0.8±0.7
Prescription 1 0.5±0.5
Prescription 2 0.4±0.5
Prescription 3 0.6±0.4
Contrast 1 0.7±0.5
3.2 on serum MDA and the impact of SOD level
Compared with Normal group, model group, contrast groups and each treatment group serum MDA and SOD level are all without significantly changing Become, be shown in Table 22.
Table 22 on the impact of rat bone arthritis model serum MDA and SOD level (n=8,)
Group MDA(nmol/L) SOD(NU/ml)
Matched group 6.2±1.5 115.2±12.6
Model group 6.5±2.0 114.1±15.7
Prescription 1 6.3±1.5 112.0±13.8
Prescription 2 6.4±1.6 116.9±15.1
Prescription 3 6.3±1.7 114.6±12.6
Contrast 1 6.2±1.4 113.7±11.5
3.3 impacts on articular cartilage proteoglycan content
After modeling 3 weeks, compared with matched group, in model group cartilaginous tissue, proteoglycan content significantly reduces (P ＜ 0.05). 3 present composition groups improve more apparent (P ＜ 0.05), Dan Baiduotang proteoglycan PG in 1 present composition contrast groups cartilaginous tissue Content significantly reduces (P ＜ 0.05), is shown in Table 23.
Table 23 on the impact of rat bone arthritis model articular cartilage proteoglycan content (n=8,)
Group Dan Baiduotang proteoglycan PG (μ g chrondroitin/mg cartilage dry weight)
Matched group 49.7±14.1
Model group 32.4±6.1<sup>*</sup>
Prescription 1 39.1±5.5#
Prescription 2 39.8±7.3#
Prescription 3 38.7±7.9#
Contrast 1 33.9±7.3<sup>*</sup>
*P ＜ 0.05, compares with matched group；#P ＜ 0.05, compares with model group
3.4 histopathological examination
Each group cartilage and Synovial histopathology check that result shows, each group cartilage surface is smooth, is showed no obvious hypertrophy, The cell infiltration that quantity does not waits is seen by model group synovial membrane undertissue, and compared with model group, 3 groups of compositionss of the present invention are caused to experiment In rat bone arthritis, the lesions of synovium contributed all has certain therapeutical effect.
4 brief summaries
After this test modeling 3 weeks, there is pathological changes in various degree, chondroproteoglycan content in rat articular synovial membrane and cartilage Reducing, above-mentioned change is improved significantly by the present composition, and compositions of the present invention lures for papain Lead rabbit cartilage degraded osteoarthritis and there is obvious curative effects.
Embodiment 3, the Evaluation of Functional of analgesic activity
1. Dichlorodiphenyl Acetate causes the impact of mouse writhing reaction
1.1 dosage and packet
Selecting healthy ICR kind white mice 60, male and female half and half, body weight 18～22g, test sets 6 groups altogether, respectively model group (0.5%CMC-Na), positive drug group (aspirin 200mg/kg), present composition group (3 compositions proportionings are shown in Table 24), Often 10 animals of group, respectively combine respective concentration suspension, are administered volume and are 10ml/kg.
Table 24 present composition different ratio is arranged
Chondroitin sulfate Glucosamine hydrochloride Radix Puerariae extract Calcium carbonate Hyaluronic acid Dimethyl sulfone
Prescription 1 16.2% 37.8% 10.9% 30.1% 3.7% 1.3%
Prescription 2 27% 27% 10.9% 30.1% 3.7% 1.3%
Prescription 3 37.8% 16.2% 10.9% 30.1% 3.7% 1.3%
Contrast 1 27.6% 27.7% 10.9% 30.1% 3.7% 0%
1.2 induced pains and medication
Fasting 12h before the test of each treated animal, drinking-water does not limits.After gavage gives relative medicine 30min, lumbar injection 0.6% Acetic acid (0.2ml/ is only), after record injection, in 15min, there is the number of times of writhing in mice.Occur that waist muscle is received repeatedly with mice Contracting, hogback, buttocks torsion and hindlimb extension are that writhing response is positive.By following equation calculating Drug inhibition writhing percentage rate:
Suppression ratio (%)=(matched group writhing number-administration group writhing number)/matched group writhing number × 100%
1.3 result
Positive drug group, 3 present composition groups and 1 present composition contrast groups can substantially reduce mouse writhing Number of times, is shown in Table 25.
Table 25 Dichlorodiphenyl Acetate cause mouse writhing reaction impact (n=10,)
Group Writhing number
Matched group 31±8
Model group 17±10<sup>**</sup>
Prescription 1 20±16<sup>**</sup>
Prescription 2 18±8<sup>**</sup>
Prescription 3 20±10<sup>**</sup>
Contrast 1 23±16<sup>**</sup>
**P ＜ 0.01 compares with model group.
2. mice burning pain is erected the impact of tail pain threshold
2.1 dosage and packet
Selecting healthy ICR kind white mice 60, male and female half and half, body weight 18～22g, test sets 6 groups altogether, respectively model group (0.5%CMC-Na), positive drug group (aspirin 200mg/kg), present composition group (being shown in Table 27), often group 10 animals, Respectively combine respective concentration suspension, be administered volume and be 10ml/kg.
2.2 induced pains and medication
Healthy male ICR mouse, body weight 18～22g, random packet, before test, each group mice overnight fasting, tests the same day The each group corresponding test medicine of gavage (respectively assembling variable concentrations processed), different time is by mouse tail lower vertical before being administered and after administration Immerse in (50.0 ± 0.5 DEG C) water bath with thermostatic control, immerse about length 3cm, with tail bounce back out incubation period of the water surface for surveying pain index, As pain threshold.Pain threshold before mensuration is administered respectively 2 times, takes the threshold of pain based on its meansigma methods.Gavage gives relative medicine After, measure be administered after 0.5,1, the pain threshold of each mice of 2h.
Mice burning pain is erected the impact of tail pain threshold by 2.3
Positive drug group, 3 present compositions and 1 contrast groups of the present invention can significantly improve mice burning pain threshold value (P ＜ 0.05, P ＜ 0.01), it is shown in Table 26.
Table 26 mice burning pain is erected the impact of tail pain threshold (n=10,)
*P ＜ 0.05,**P ＜ 0.01 compares with model group.
3 brief summaries
The present composition can substantially reduce mouse writhing number of times, can significantly improve mice burning pain threshold value.The prompting present invention Compositions has certain analgesic activity.
By the related experiment result of above-described embodiment 1～3 it can be seen that the present composition by six kinds of compositions with most preferably than Example combines, and in addition to having and preferably increasing bone substance density improving function, said composition also has alleviation arthralgia, repairs and promote Enter regenerating bone or cartilage, suppression bone metabolism, lubricating joint and delay the function of osteoarthritis progression, can obviously relieve Human Osteoarthritis Clinical symptoms.
Embodiment 4
A kind of film coating tablet with the compositions increasing bone density, anti-inflammatory and analgesic effect, raw material components is as follows:
Chondroitin sulfate 150g, glucosamine hydrochloride 350g, Radix Puerariae extract 101g, calcium carbonate 280g, hyaluronic acid Sodium 34g, dimethyl sulfone 12.5g, microcrystalline Cellulose 303g, PVP K30 11g, PVPP 5.5g, magnesium stearate 5.5g, gastric solubleness Type pharmaceutical films coating materials 22g.
The preparation method of above-mentioned film coating tablet, step is as follows:
I Radix Puerariae extract is individually pelletized by (), cross 20 mesh sieves, granulate, prepare Radix Puerariae extract granule；
(ii) by mass percentage concentration 8～12% ratio film coating agent is dissolved in the second that volumetric concentration is 70% In alcoholic solution, prepare film coating liquid；
(iii) hyaluronate sodium, dimethyl sulfone and microcrystalline Cellulose, PVPP, magnesium stearate, PVP K30 are passed through Radix Puerariae extract prepared with chondroitin sulfate, glucosamine hydrochloride, calcium carbonate, step (i) after amount incremental method mix homogeneously Granule mix homogeneously, uses wet granulation, tabletting, uses the film coating liquid coating that step (ii) is prepared, and tablet weight is 1.1g/ Sheet, is pressed into 1000, to obtain final product.
Embodiment 5
A kind of film coating tablet with the compositions increasing bone density, anti-inflammatory and analgesic effect, component is as follows:
Chondroitin sulfate 250g, glucosamine hydrochloride 250g, Radix Puerariae extract 101g, calcium carbonate 280g, hyaluronic acid Sodium 34g, dimethyl sulfone 12.5g, microcrystalline Cellulose 153g, PVP K30 11g, PVPP 5.5g, magnesium stearate 5.5g, gastric solubleness Type pharmaceutical films coating materials 22g.
Preparation method is with embodiment 4.
Embodiment 6
A kind of film coating tablet with the compositions increasing bone density, anti-inflammatory and analgesic effect, component is as follows:
Chondroitin sulfate 350g, glucosamine hydrochloride 150g, Radix Puerariae extract 101g, calcium carbonate 280g, hyaluronic acid Sodium 34g, dimethyl sulfone 12.5g, microcrystalline Cellulose 2.2g, PVP K30 11g, PVPP 5.5g, magnesium stearate 5.5g, gastric solubleness Type pharmaceutical films coating materials 22g.
Preparation method is with embodiment 4.

Claims (10)

1. one kind has increase bone density, the compositions of anti-inflammatory and analgesic effect, it is characterised in that crude drug component is as follows, is Weight portion:
Chondroitin sulfate 10～60 parts, glucosamine hydrochloride 10～60 parts, calcium carbonate 10～50 parts, hyaluronate sodium 1～10 Part, dimethyl sulfone 1～10 parts, Radix Puerariae extract 1～20 parts.
2. compositions as claimed in claim 1, it is characterised in that the percent mass of Radix Puerariae isoflavone in described Radix Puerariae extract It is not less than 40% than content.
3. compositions as claimed in claim 1, it is characterised in that crude drug component is as follows, is weight portion:
Chondroitin sulfate 20～40 parts, glucosamine hydrochloride 20～40 parts, calcium carbonate 20～35 parts, hyaluronate sodium 2～5 Part, dimethyl sulfone 1～2 parts, Radix Puerariae extract 8～12 parts.
4. compositions as claimed in claim 3, it is characterised in that crude drug component is as follows, is weight portion:
Chondroitin sulfate 27 parts, glucosamine hydrochloride 27 parts, calcium carbonate 30 parts, hyaluronate sodium 4 parts, dimethyl sulfone 1 part, Pueraria lobota Root extract 11 parts.
5. have increase bone density described in claim 1, the compositions of anti-inflammatory and analgesic effect has increase bone density in preparation, resists Application in the health product of scorching analgesic activity.
Apply the most as claimed in claim 5, it is characterised in that the dosage form of described health product is tablet, granule, capsule； It is further preferred that described tablet is film coating tablet, dispersible tablet, buccal tablets, chewable tablet.
7. having the film coating tablet of the compositions increasing bone density, anti-inflammatory and analgesic effect described in claim 1, its feature exists In, component is as follows, is weight portion:
Crude drug 120～200 parts, filler 0.1～50 parts, disintegrating agent 0.1～2 parts, lubricant 0.1～2 parts, binding agent 1～3 Part, film coating agent 3～5 parts.
8. film coating tablet as claimed in claim 7, it is characterised in that described filler is microcrystalline Cellulose；Preferably, Described disintegrating agent is polyvinylpolypyrrolidone (PVPP)；Preferably, described lubricant is magnesium stearate；Preferably, described binding agent is PVP K30.
9. film coating tablet as claimed in claim 7, it is characterised in that described film coating agent is stomach dissolution type pharmaceutical films Coating materials.
10. the preparation method of film coating tablet described in claim 7, it is characterised in that step is as follows:
I Radix Puerariae extract is individually pelletized by (), cross 20 mesh sieves, granulate, prepare Radix Puerariae extract granule；
(ii) by mass percentage concentration 8～12% ratio that film coating agent is dissolved in the ethanol that volumetric concentration is 70% is molten In liquid, prepare film coating liquid；
(iii) hyaluronate sodium, dimethyl sulfone and filler, disintegrating agent, lubricant, binding agent are mixed by equal increments method Radix Puerariae extract granule prepared with chondroitin sulfate, glucosamine hydrochloride, calcium carbonate, step (i) after uniformly is mixed homogeneously, Use wet granulation, tabletting, use the film coating liquid coating that step (ii) is prepared, to obtain final product.
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CN112535706A (en) * 2020-12-16 2021-03-23 解中胜 Medicine and food dual-purpose powder for repairing joints and preparation method and application thereof
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CN112535706A (en) * 2020-12-16 2021-03-23 解中胜 Medicine and food dual-purpose powder for repairing joints and preparation method and application thereof
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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