CN1316978C - Compound glucosamine sulfate dispersible tablet formulation and its preparation method - Google Patents
Compound glucosamine sulfate dispersible tablet formulation and its preparation method Download PDFInfo
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- CN1316978C CN1316978C CNB2005100296938A CN200510029693A CN1316978C CN 1316978 C CN1316978 C CN 1316978C CN B2005100296938 A CNB2005100296938 A CN B2005100296938A CN 200510029693 A CN200510029693 A CN 200510029693A CN 1316978 C CN1316978 C CN 1316978C
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- gram
- glucosamine sulfate
- polyvinylpolypyrrolidone
- glucosamine
- sulfate
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- 229960002849 glucosamine sulfate Drugs 0.000 title claims abstract description 48
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims abstract description 16
- 238000009472 formulation Methods 0.000 title claims abstract description 14
- -1 Compound glucosamine sulfate Chemical class 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims description 13
- MTDHILKWIRSIHB-UHFFFAOYSA-N (5-azaniumyl-3,4,6-trihydroxyoxan-2-yl)methyl sulfate Chemical compound NC1C(O)OC(COS(O)(=O)=O)C(O)C1O MTDHILKWIRSIHB-UHFFFAOYSA-N 0.000 claims abstract description 34
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229920001287 Chondroitin sulfate Polymers 0.000 claims abstract description 29
- 229940059329 chondroitin sulfate Drugs 0.000 claims abstract description 29
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 26
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 25
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 25
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims abstract description 25
- 229920002472 Starch Polymers 0.000 claims abstract description 17
- 235000019698 starch Nutrition 0.000 claims abstract description 17
- 239000008107 starch Substances 0.000 claims abstract description 17
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- 239000003826 tablet Substances 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000011780 sodium chloride Substances 0.000 claims description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 14
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a compound glucosamine sulfate dispersible tablet formulation which belongs to the technical field of medicine. The formulation has the principal components of glucosamine sulfate and chondroitin sulfate, and auxiliary materials which comprise excipients, such as starch and microcrystalline cellulose, a disintegrating agent, such as polyvinylpolypyrrolidone, a lubricating agent, such as magnesium stearate, and a wetting agent, such as anhydrous alcohol. The formulation is prepared by sieving appropriate weight proportion and by a definite technology. Compared with an ordinary tablet, the dispersible tablet formulation has the advantages of obviously excellent dispersivity, and rapid dissolution and drug effect.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of Compound glucosamine sulfate dispersible tablet formulation and its preparation method that is used for the treatment of osteoarthritis.
Background technology
Osteoarthritis (Osteoarthritis, OA) be a kind of degenerative joint disease that incidence rate obviously increases with age growth, claim proliferative arthritis, degenerative osteoarthritis or osteoarthritis again, it is modal joint disease, also be the common cause that causes the middle-aged and elderly people arthralgia, have a strong impact on the quality of life of middle-aged and elderly people.
Because aged tendency of population in the prolongation of human average life and the world wide, medical care problem that countries in the world are relevant with OA and medical expense also sharply increase, and the social productive forces loss and the extra financial burden that are brought because of function and labour force's forfeiture also sharply increase thereupon.Estimate that according to WHO in the present global population, 10% medical care problem comes from OA.
The sickness rate of OA is higher.According to China's preliminary survey OA incidence rate is 3%, i.e. 3,600 ten thousand patients are the same substantially with U.S. incidence rate.Show that according to another Epidemiological study China OA prevalence is about 10%, the old people OA prevalence more than 60 years old is up to 50%, and along with the increase OA prevalence straight line at age rises.The ranks of world aging country are gone in China's stride, and population surpasses 100,000,000 more than 60 years old, estimate that OA patient is about 50,000,000.Estimate that following maximum OA patient crowd will be in China.
In a word, OA increases sharply to the mankind's threat, and effectively preventing and treating OA becomes one of key of improving people quality of life, also is an important problem of orthopedics circle.
The medicine of treatment OA is divided into nonspecific drug and specific drug two big classes at present.Nonspecific drug mainly comprises oral non-opium analgesic, NSAID (non-steroidal anti-inflammatory drug) (NSAID) and intraarticular injection glucocorticoid etc.Light for clinical inflammation performance, only, consider earlier regularly or oral in case of necessity analgesics based on the patient of pain, external first-selected acetaminophen, analgesic effect is obvious, but the report of pair liver, renal damage is arranged after long-term the extensive application; For the heavier patient of the inflammation in joint, NSAID is still traditional first-selected medication, common drug have diclofenac, ibuprofen, naproxen and former times the dry goods medicine, but untoward reaction is more, especially the gastrointestinal reaction has limited its prolonged application.If this class drug main antiinflammatory, pain relieving, i.e. doing well,improving medicine, but can not mitigate the disease, if improper use, even increase the weight of the state of an illness, as the intraarticular injection glucocorticoid, can further destroy cartilage, cause articular degeneration.
Specific drug is that exploitation in nearest about 10 years is used for the treatment of the medicine of OA, also claims to do slowly the pathological process that medication, this class medicine can stop or slow down OA, suppresses to cause the correlation factor of tissue injury and articular cartilage degeneration.Slowly act on medicated bag and draw together glucosamine sulfate, chondroitin sulfate, diacerein and intraarticular injection hyaluronic acid etc.Improve medicine though also be classified as the state of an illness at present without any medicine; but many effects of pointing out this medicine to have simultaneously probably to improve OA patient symptom and protection articular cartilage about the glucosamine sulfate clinical test results are the ideal medicament of treatment osteoarthritis.
Glucosamine is a kind of natural saccharide that derives from chitin; be the main component in the cartilage matrix, by changing its side-chain structure, easilier in articular cartilage combine with water; the maintenance articular cavity lubricates the effect with compensator or trimmer pressure, and impaired chondrocyte is had the certain protection effect.The symptom development of synthetic glucosamine sulfate may command OA helps the reparation of cartilage.In the U.S., the compound recipe of glucosamine and chondroitin sulfate has very high safe reliability as food additive.Oral such medicine can reach therapeutic purposes.The patient of, pulmonary disease poor with blood circulation diseases, hepatic and renal function for some, diabetes has safety equally.
26 editions NF21 of American Pharmacopeia have recorded the complex tablet of glucosamine and chondroitin sulfate.Listing is that the preparation of main component is a lot of with glucosamine and chondroitin sulfate abroad, as MaxiLIFE (glucosamine sulfate 500mg/ chondroitin sulfate 400mg, Twinlab company, 30 on chip, Chondroitin Glucosamine Complex (glucosamine sulfate 250mg/ chondroitin sulfate 200mg, National Vitamin company, 60 are encapsulated).
Cosamin
DS (glucosamine hydrochloride 500mg/ chondroitin sulfate 400mg, Nutramax Lab company, 150 69.00 dollars on chip), Osteo Joint Care (50 is on chip for glucosamine hydrochloride 750mg/ chondroitin sulfate 600mg, NBTY company), More Free
(glucosamine mixture 750mg/ chondroitin sulfate 600mg), Nutrajoint
(120 encapsulated for glucosamine hydrochloride 375mg/ chondroitin sulfate 300mg, Knox company), ARTHx
TM(90 is on chip for glucosamine hydrochloride 500mg/ chondroitin sulfate 400mg, Trace Minerals Research company) etc. is used to protect the joint as dietary supplement
[6]
But, adopt in glucosamine and the chondroitin sulfate compound medicine, mainly be capsule formulation and tablet, these dosage form onsets are slow, influenced giving full play to of drug effect.
Summary of the invention
The objective of the invention is to propose a kind of simple, rapid-action Compound glucosamine sulfate dispersible tablet formulation and its preparation method for preparing.
The compound glucosamine sulfate dispersible tablet formulation that the present invention proposes, its main composition is sour glucosamine and chondroitin sulfate, adjuvant has excipient (as starch and microcrystalline Cellulose), disintegrating agent is (as polyvinylpolypyrrolidone, add type in being divided into and add type), lubricant (as magnesium stearate) and lubricant (as dehydrated alcohol), the weight proportion of each component is as follows:
Glucosamine sulfate sodium chloride double salt 300-330 gram
Chondroitin sulfate 180-220 gram
Starch 45-55 gram
Microcrystalline Cellulose 90-110 gram
Polyvinylpolypyrrolidone 680-720 gram
Magnesium stearate 18-23 gram
Dehydrated alcohol is an amount of
The material of above-mentioned prescription is made 1000 tablets of medicines, and every weight is the 1.35-1.45 gram.
The preparation method of above-mentioned compound glucosamine sulfate dispersible tablet formulation is as follows: each supplementary material is crossed 80 mesh sieves and is pulverized; The polyvinylpolypyrrolidone (adding type in being called) of glucosamine sulfate sodium chloride double salt, chondroitin sulfate, starch, microcrystalline Cellulose and 45-55% is placed container, abundant stirring and evenly mixing, cross the granulation of 24 orders after adding the ethanol solution moistening again, 40～50 ℃ of dryings were extremely done in 1～2 hour; Add remaining polyvinylpolypyrrolidone (being called the type of adding) and magnesium stearate, then 20-25 order granulate; Tabletting behind abundant mixing and the mensuration intermediate content, every heavy 1.35-1.45 gram.
Pharmacodynamics test:
1, the inhibitory action of the rat paw edema that different proinflammatory agents are caused
Pharmacodynamics test studies show that glucosamine sulfate 200,400,800mg/kg i.g. can obviously reduce the rat paw edema that carrageenin causes.Concrete outcome sees the following form:
| Proinflammatory agent | Route of administration | Glucosamine sulfate | Aspirin | ||||
| n | ED 30(mg/kg) | t max(h) | n | ED 30(mg/kg) | t max(h) | ||
| Carrageenin | Ip Po | 60 70 | 36.1 380 | 1 1 | 25 30 | 17.8 38.3 | 1 1 |
| Kallidin I | Ip | 60 | ＞500 | 1～5 | 25 | 190 | 5 |
| Glucosan | Ip | 45 | 632 | 1 | 30 | 176 | 3 |
| Formalin | Ip | 40 | 700 | 3 | 25 | 193 | 5 |
| 5-hydroxy tryptamine | Ip | 15 | ＞600 | 1～5 | 5 | ＞800 | 1～5 |
| Histamine | Ip | 15 | ＞400 | 1～3 | 5 | 300 | 1 |
2, the inhibitory action of and subacute inflammation that subcutaneous implantation polyvinyl sponge cause swollen to rat granuloma
Experimental study is the result show, it is swollen that glucosamine sulfate 200,400,800mg/kg i.g. significantly suppress rat granuloma.
Subcutaneous rat is implanted the inhibiting following table that the results are shown in of the subacute inflammation that polyvinyl sponge causes:
| Effect to transudate | ED 30(mg/kg) | Relative intensity (P value) | |
| Glucosamine sulfate | Indomethacin | ||
| Volume leukocyte number protein content PGE 2Concentration | 570 (208～1560) 418 (320～546) 611 (171～2188) non-activities | 1.9(0.7～4.9) 2.4(1.3～4.6) 2.6(1.1～6.0) 0.9(0.3～2.5) | 0.003 0.006 0.004 fails to record |
3, glucosamine sulfate is to the granulomatous inhibitory action of Oleum Tiglii
| Effect | ED 30(mg/kg) | Relative intensity (P value) | |
| Glucosamine sulfate | Indomethacin | ||
| Transudate volume granulation tissue weight | 664(238～1849) 631(149～2679) | 2.1(1.5～2.9) 3.6(0.7～18) | 0.003 0.006 |
4, the inhibitory action of glucosamine sulfate articulatio tibiotarsalis inflammation that kaolin is caused
| Effect | ED 30(mg/kg) | Relative intensity (P value) | |
| Glucosamine sulfate | Indomethacin | ||
| The blue amount injection of Evans parapodum sole of the foot volume | 531(272～1038) 833(513～1521) | 2.9(1.5～6) 8.4(2.5～29) | 0.003 0.01 |
5, glucosamine sulfate is to the effect of rat assist agent arthritis
Experimental study is the result show, glucosamine sulfate 100,200,400mg/kg i.g. can obviously suppress partial early stage inflammatory reaction of rat injection adjuvant and the swelling once again after 14 days, and can obviously suppress the pedal swelling that the offside hind leg causes because of delayed hypersensitivity, can reduce the nodular appearance of afterbody simultaneously.
| Effect | ED 30(mg/kg) | Relative intensity (P value) | |
| Glucosamine sulfate | Indomethacin | ||
| Arthritis incidence rate injection parapodum sole of the foot volume is to parapodum sole of the foot volume tuberosity number | 184(76～446) 229(148～353) 111(63～194) 49(3～855) | 0.9(0.3～3) 1.5(0.5～5) 1.9(0.6～6) 1.1(0.4～3) | 0.005 0.007 0.02 0.02 |
6, the inhibitory action that increases of the capillary permeability that proinflammatory agent is caused
| Model | Route of administration | Glucosamine sulfate | Aspirin | ||
| n | ED 30(mg/kg) | n | ED 30(mg/kg) | ||
| Rat: capillary permeability increases due to the Kallidin I | po | 16 | ＞400 | 16 | 45 |
| Rat: pleuritis soaks into rat to exudate to granulocyte due to the carrageenin: formalin causes the peritonitis mice: acetic acid causes peritonitis | po po ip po | 30 30 36 30 | 532 315 738 275 | 5 5 24 20 | 30 28 8.9 1.13 |
Compound basis of the present invention
Glucosamine sulfate oral 90% is absorbed, and permeates into blood rapidly, and is distributed to tissue and organ, still keeps 30% through first pass metabolism artifact activity.Blood drug level reaches peak value behind the oral 4h, and the half-life is 18h.Glucosamine is less molecule through liver metabolism, finally becomes carbon dioxide, water and carbamide.The medicine about 10% that absorbs is discharged from feces, and about 20%～30% can come across in the urine, and nearly 70% glucosamine is with CO
2Form is breathed out, and 8%～10% is retained in the tissue.Chondroitin sulfate to rat and Canis familiaris L. oral administration after, absorbance is greater than 70%, and can find in urine and tissue.The peak time of high molecular chrondroitin is respectively 1.6 and 2.1h in the blood plasma of rat and Canis familiaris L., through still existing in blood plasma behind the 36h.Drug level in 24h rear intestinal, liver, kidney, synovial membrane liquid and the cartilage is higher than its hetero-organization.
The compound preparation of glucosamine sulfate and chondroitin sulfate is that the ideal osteoarthritis state of an illness is improved medicine, solely uses as prescription drugs at China and this two prescription of EU member country, in the North America as the OTC preparation that then compound recipe replenished as food of the U.S., Canada.
Prescription screening
Because the present invention is a dispersible tablet formulation, for prescription, we investigate the particulate flowability and the uniformity, and it disperses homogeneity and friability high spot reviews, finds best ratio of adjuvant.
Design prescription following (feeding intake) by 100
| R X1 | R X2 | R X3 | R X4 | R X5 | R X6 | |
| Glucosamine Sulphate sodium chloride double salt (g) chondroitin sulfate (g) starch (g) microcrystalline cellulose (g) cross-linked pvp (g) L-HPC (g) 5%PVP alcohol absolute ethyl alcohol dolomol (g) talcum powder (g) | 31.4 20 / / / 50 Q·s / / 0.5 | 31.4 20 10 20 / 50 Q·s / / 1 | 31.4 20 10 20 50 / Q·s / 1 / | 31.4 20 10 10 70/an amount of 2/ | 31.4 20 10 10 35/an amount of 2/ | 31.4 20 5 10 35/an amount of 2/ |
| Micropowder silica gel (g) adds cross-linked pvp (g) | / / | / / | / / | 2 / | / 35 | / 35 |
| Prescription is estimated | R X1 | R X2 | R X3 | R X4 | R X5 | R X6 |
| Granule angle of repose (α) sheet friability (%) disperses homogeneity | 38° 0.105 ＞5′ | 33° 0.135 ＞5′ | 31° 0.162 3′15″ | 32° 0.176 2′10″ | 32° 0.181 1′20″ | 30° 0.192 1′ |
Experiment is discussed
Investigation raw material influence is at first selected full raw material and is added disintegrating agent L-HPC about 50%, investigates its disintegrate situation, but it is bigger for its material quantity, and be crystalline powder after pulverizing,, can't form granule substantially so the granulation rear formability is poor, after suitable pressure compacting in flakes, disperse homogeneity defective,, consider to add therein excipient considerably beyond 3 minutes, consider the disintegrate effect simultaneously, draft adding starch and microcrystalline Cellulose.After adding excipient, granular mass improves, but the disintegrate effect is still relatively poor, consider to change disintegrating agent, draft and add the super-disintegrant cross-linked pvp, disintegrate improves after adding cross-linked pvp, thus strengthen consumption make reach sheet heavy 50%, disperse this moment the homogeneity can qualified (＜3 ').On this basis, we select a cross-linked pvp part to be used for adding, and further reduce disintegration time to improve disintegrate efficient.Consider at last to reduce amount of excipient, under the situation that reduces the starch consumption a little, still can guarantee grain forming, and disintegration time reduces once more.True thus present compound recipe component and proportioning.
The stripping of compound dispersed tablet of the present invention and compound glucosamine sulfate ordinary tablet relatively
Above-mentioned experimental result shows that the dispersibility of compound glucosamine sulfate dispersible tablet obviously is better than ordinary tablet, and stripping is fast, embodies the characteristics of dispersible tablet, and the combined influence factor is investigated the presentation of results prescription rationally, feasible process.
The specific embodiment
The invention is further illustrated by the following examples.
Embodiment 1
The prescription of dispersible tablet is;
Glucosamine sulfate sodium chloride double salt 314 grams
Chondroitin sulfate 200 grams
Starch 50 grams
Microcrystalline Cellulose 100 grams
Polyvinylpolypyrrolidone (in add type) 350 grams
Polyvinylpolypyrrolidone (adding type) 350 grams
Magnesium stearate 20 grams
Dehydrated alcohol 16 grams
Make 1000 altogether, every is 1.4 grams.
Glucosamine sulfate is 250 grams in the 314 gram glucosamine sulfate sodium chloride double salt.
Preparation process: each supplementary material is crossed 80 mesh sieves and is pulverized; Glucosamine sulfate sodium chloride double salt, chondroitin sulfate, starch, microcrystalline Cellulose and polyvinylpolypyrrolidone (in add type) are placed fully stirring and evenly mixing of container, add again and cross 20 orders after the ethanol solution moistening and granulate, 45 ℃ of dryings 75 minutes; Add remaining polyvinylpolypyrrolidone (adding type) and magnesium stearate, then 24 order granulate; Abundant mixing, tabletting behind the mensuration intermediate content.
Embodiment 2
The prescription of dispersible tablet is;
Glucosamine sulfate sodium chloride double salt 314 grams
Chondroitin sulfate 196 grams
Starch 55 grams
Microcrystalline Cellulose 105 grams
Polyvinylpolypyrrolidone (in add type) 340 grams
Polyvinylpolypyrrolidone (adding type) 350 grams
Magnesium stearate 22 grams
Dehydrated alcohol 18 grams
Make 1000 altogether, every is 1.4 grams.
Preparation process: each supplementary material is crossed 80 mesh sieves and is pulverized; Glucosamine sulfate sodium chloride double salt, chondroitin sulfate rope, starch, microcrystalline Cellulose and polyvinylpolypyrrolidone (in add type) are placed fully stirring and evenly mixing of container, add again and cross 24 orders after the ethanol solution moistening and granulate, 40 ℃ of dryings 90 minutes; Add remaining polyvinylpolypyrrolidone (adding type) and magnesium stearate, then 24 order granulate; Abundant mixing, tabletting behind the mensuration intermediate content.
Embodiment 3
The prescription of dispersible tablet is;
Glucosamine sulfate sodium chloride double salt 314 grams
Chondroitin sulfate 206 grams
Starch 50 grams
Microcrystalline Cellulose 94 grams
Polyvinylpolypyrrolidone (in add type) 345 grams
Polyvinylpolypyrrolidone (adding type) 355 grams
Magnesium stearate 20 grams
Dehydrated alcohol 16 grams
Make 1000 altogether, every is 1.4 grams.
Preparation process: each supplementary material is crossed 80 mesh sieves and is pulverized; Glucosamine sulfate sodium chloride double salt, chondroitin sulfate, starch, microcrystalline Cellulose and polyvinylpolypyrrolidone (in add type) are placed fully stirring and evenly mixing of container, add again and cross 24 orders after the ethanol solution moistening and granulate, 50 ℃ of dryings 60 minutes; Add remaining polyvinylpolypyrrolidone (adding type) and magnesium stearate, then 24 order granulate; Abundant mixing, tabletting behind the mensuration intermediate content.
Embodiment 4
The prescription of dispersible tablet is;
Glucosamine sulfate sodium chloride double salt 314 grams
Chondroitin sulfate 200 grams
Starch 45 grams
Microcrystalline Cellulose 100 grams
Polyvinylpolypyrrolidone (in add type) 360 grams
Polyvinylpolypyrrolidone (adding type) 348 grams
Magnesium stearate 18 grams
Dehydrated alcohol 15 grams
Make 1000 altogether, every is 1.4 grams.
Preparation process: each supplementary material is crossed 80 mesh sieves and is pulverized; Glucosamine sulfate sodium chloride double salt, chondroitin sulfate, starch, microcrystalline Cellulose and polyvinylpolypyrrolidone (in add type) are placed fully stirring and evenly mixing of container, add again and cross 24 orders after the ethanol solution moistening and granulate, 40 ℃ of dryings 120 minutes; Add remaining polyvinylpolypyrrolidone (adding type) and magnesium stearate, then 24 order granulate; Abundant mixing, tabletting behind the mensuration intermediate content.
The prepared glucosamine sulfate dispersible tablet formulation of the foregoing description all has good dispersibility, and stripping is fast, and the drug effect onset is rapid.
Claims (2)
1, a kind of compound glucosamine sulfate dispersible tablet formulation is characterized in that the weight proportion of component is as follows:
Glucosamine sulfate sodium chloride double salt 300-330 gram
Chondroitin sulfate 180-220 gram
Starch 45-55 gram
Microcrystalline Cellulose 90-110 gram
Polyvinylpolypyrrolidone 680-720 gram
Magnesium stearate 18-23 gram
Dehydrated alcohol is an amount of
Wherein, the amount of polyvinylpolypyrrolidone adds type and adds type two parts consumption sum in being,
The material of above-mentioned prescription is made 1000 tablets of medicines, and every weight is the 1.35-1.45 gram.
2, a kind of preparation method of compound glucosamine sulfate dispersible tablet formulation as claimed in claim 1 is characterized in that concrete steps are as follows: each supplementary material is crossed 80 mesh sieves and is pulverized; The polyvinylpolypyrrolidone of glucosamine sulfate sodium chloride double salt, chondroitin sulfate, starch, microcrystalline Cellulose and 45-55% is placed container, abundant stirring and evenly mixing, cross the granulation of 24 orders after adding the ethanol solution moistening again, 40～50 ℃ of dryings were extremely done in 1～2 hour; Add remaining polyvinylpolypyrrolidone and magnesium stearate, then 20-25 order granulate; Tabletting behind abundant mixing and the mensuration intermediate content, every heavily is the 1.35-1.45 gram.
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| CN102228466A (en) * | 2011-03-25 | 2011-11-02 | 上海优能慧斯生物科技有限公司 | Chondroitin sulfate glucosamine tablets |
| CN104873534A (en) * | 2015-04-03 | 2015-09-02 | 广东先强药业有限公司 | Glucosamine chondroitin tablets and preparation technology thereof |
| CN110507620B (en) * | 2019-09-09 | 2021-05-11 | 山东润德生物科技有限公司 | Compound glucosamine sulfate dispersible tablet and preparation method thereof |
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| 氨基葡萄糖和硫酸软骨素含量测定方法的建立 翟咏红等，药物鉴定，第14卷第4期 2005 * |
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