CN1771973A - Composite medicine containing nonsteroidal anti-inflammatory analgetic and its prepn - Google Patents
Composite medicine containing nonsteroidal anti-inflammatory analgetic and its prepn Download PDFInfo
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- CN1771973A CN1771973A CN 200510012938 CN200510012938A CN1771973A CN 1771973 A CN1771973 A CN 1771973A CN 200510012938 CN200510012938 CN 200510012938 CN 200510012938 A CN200510012938 A CN 200510012938A CN 1771973 A CN1771973 A CN 1771973A
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Abstract
The present invention constitutes compound medicine with nonsteroidal anti-inflammatory analgetic with aminoglucose and nonsteroidal anti-inflammatory analgetic. Compared with aminoglucose or nonsteroidal anti-inflammatory analgetic, the compound medicine of aminoglucose and nonsteroidal anti-inflammatory analgetic has raised curative effect, lowered toxic side effect, and raised patient compliance. The prepared eye preparation may be also used for noninfectious inflammation of eyes.
Description
Technical field
The present invention relates to a kind of anti-inflammatory analgesic, be used for the treatment of knee joint, lumbar vertebra, cervical vertebra degenerative osteoarthritis, composition of medicine of and the medicine of rheumatic, rheumatoid arthritis, scapulohumeral periarthritis and the non-infectious inflammation of ophthalmology-contain nonsteroidal anti-inflammatory analgetic (NSAIDs) and glucosamine and preparation method thereof.
Background technology
Osteoarthritis (Osteoarthritis, OA) claim osteoarthritis, osteoarthritis, senile arthritis, proliferative arthritis, hypertrophiarthritis again, be divided into constitutional arthritis and Secondary cases arthritis, the regression of articular cartilage is the basic reason of its morbidity.Be characterized in that pain, inflammation, stiff, enlargement, deformity and dysfunction appear in hands, wrist, ankle, knee joint, hip, shoulder, spinal joint etc., the articular cartilage of human body inevitably takes place to degenerate and wearing and tearing with advancing age, the regression of cartilage promptly began from 20 years old later stage, in crowd more than 50 years old, big multipotency shows the performance of osteoarthritis on the X sheet, the old man of over-65s nearly all suffers from tangible osteoarthritis, so osteoarthritis is the commonly encountered diseases and the frequently-occurring disease of middle-aged and elderly people, pathological changes is often more outstanding than the male in the women.Along with social population's aging, the generation of osteoarthritis is more and more.Osteoarthritis affects a big chunk in the whole world population.Along with the aggravation and the activity of arthralgia are obstructed, will cause temporary transient or permanent disablement, bring heavy losses in society and economic aspect.
Nonsteroidal anti-inflammatory analgetic thing (NSAIDs) is effective prostaglandin synthesis inhibitors, has tangible antiinflammatory, analgesic activity.Disturb inflammatory process by a plurality of links, as the degeneration of inflammation-inhibiting histone, it is synthetic to suppress prostaglandin by inhibition epoxidase (COX), suppress hyaluronidase and inflammatory mediator release etc., bring into play its anti-inflammatory analgesic effect, NSAIDs has important function aspect the pain of releasing arthritis class disease and the inflammatory symptom, but the common serious adverse reaction of this class medicine is to have GI irritation, lesions of liver and kidney etc., and it is closely related that this and its mechanism of action one suppresses epoxidase (COX).For the Osteoarthritis in aged patient and the bigger patient of complication danger is arranged, use separately that the nonsteroidal antiinflammatory and analgesic medicine may bring obviously and than serious adverse.
Bone articular cartilage wearing and tearing, the institute that degenerates cause that arthralgia, partly cause are to cause because of articular cartilage proteoglycan resulting anomaly.Glucosamine is a kind of natural amino monosaccharide, it is the synthetic precursor substance of proteoglycan, it is the fundamental component of chondroitin sulfate, can stimulate the proteoglycan that chondrocyte produces normal polymer structure, improve the repair ability of chondrocyte, the enzyme such as collagenase and the phospholipase A 2 that suppress the damage cartilage, and can prevent the generation of the super oxyradical of damaging cells, can promote the repair and reconstruction of cartilage matrix, thereby can delay the pathological process of bone joint pain and the process of disease, improve joint motion, alleviating pain; And can prevent by non-steroidal anti-inflammatory drug (NSAIDs) the synthetic harmful effect that causes of prostaglandin, and the release that can reduce the interior virulence factor of damaging cells, thereby reduce the original toxic and side effects of NSAIDs, can also prevent the infringement of glucocorticoid simultaneously chondrocyte.Studies show that glucosamine is present unique biosynthetic medicine that can recover the glycoprotein of destroyed in the osteoarthritis, and can stop the outbreak of osteoarthritis.Glucosamine is the same with ibuprofen effective for the treatment of knee joint osseous arthritis, and better efficacy, and especially after two weeks of drug withdrawal, the curative effect of glucosamine group is better than the ibuprofen group, and both difference has statistical significance.The more important thing is that side effect is little, and patient obviously is better than ibuprofen to the toleration of glucosamine.Therefore, glucosamine should be thought of as the choice drug of osteoarthritis treatment, especially needs the patient of long-term treatment even more important for those.
Therefore, the present invention is prepared into composition of medicine with nonsteroidal anti-inflammatory analgetic (NSAIDs) and glucosamine, curative effect can improved, reduce poisonous side effect of medicine, strengthen patient's compliance aspect and be subjected to good effect, especially needing the patient of long-term treatment at those should be a kind of ideal pharmaceutical composition.
Summary of the invention
The present invention is directed to single glucosamine pain and inflammatory symptom of releasing arthritis class disease patient rapidly used, single can bring obvious and than serious adverse with nonsteroidal anti-inflammatory analgetic (NSAIDs), and can not fundamentally treat the deficiency of such disease, NSAIDs and glucosamine are made compound medicine, remedied not enough separately, reach the raising curative effect, reduced poisonous side effect of medicine, strengthened the purpose of patient's compliance; The ophthalmic preparation of making can also be used for the non-infectious inflammation that ophthalmologic operation or non-operation factor cause.
The common medicinal forms of glucosamine has derivants such as glucosamine hydrochloride, glucosamine sulphate monomer, Glucosamine Sulfate Potassium salt, glucosamine sodium sulfate salt and the N-acetylglucosamine dimethoxym ethane of developing recently, N-acetylglucosamine, and they can be feedstock production with the chitin.Chitin has another name called chitin, be by N-acetyl group glucose by β-1, the linear polysaccharide polymer that the 4-glycosidic bond is formed by connecting, glucosamine are by natural chitin extraction, are the main components of chondroitin sulfate.Therefore, in the present invention, with the NSAIDs compatibility can be glucosamine, also can be sulfate monomer or sulphuric acid potassium salt, the sodium sulfate salt etc. of glucosamine, also can be derivants such as N-acetylglucosamine dimethoxym ethane, N-acetylglucosamine, also can be materials such as the chitin that can be decomposed into glucosamine, chrondroitin.Wherein monomeric purity of glucosamine sulphate and biological transformation ratio are better than hydrochlorate, sulphuric acid potassium salt and sodium sulfate salt, and the human body trans-utilization rate of derivants such as N-acetylglucosamine dimethoxym ethane, N-acetylglucosamine is excellent good, be better than other derivant, have more the use prospect.
Nonsteroidal anti-inflammatory analgetic described in the present invention (NSAIDs) is meant: ibuprofen, naproxen (or naproxen sodium), oxaprozin, fenoprofen calcium, flurbiprofen, loxoprofen (loxoprofen sodium), pranoprofen, diclofenac sodium (potassium), lornoxicam, etodolac, clofenamic acid, piroxicam, indomethacin, acemetacin, nabumetone, sulindac, diclofenac sodium (or diclofenac potassium), ketorolac trometamol, meloxicam and celecoxib.Their mechanism of action mainly is to suppress prostaglandin by inhibition epoxidase (COX) to synthesize, suppress hyaluronidase and inflammatory mediator release, the degeneration of inflammation-inhibiting histone etc., bring into play its anti-inflammatory analgesic effect, curative effect that shows though each concrete NSAIDs is different to the selectivity of COX1 and COX2 and untoward reaction such as GI irritation, lesions of liver and kidney strong and weak different adds with all reducing its original untoward reaction behind the glucosamine.Below be to be the clinical trial that example is carried out with the acemetacin:
Purpose: use random contrast clinical trial (randomized controlledtrial, RCT) method relatively use on the acemetacin basis with and without glucosamine (GLA) to adult's activeness quasi-wind gateway patients clinical curative effects; And relatively two kinds of influences that therapeutic scheme changes rheumatoid arthritis (RA) patient quality of life, thereby the clear and definite necessity that in the NSAIDs therapeutic scheme, adds GLA.Method: 132 routine patients adopt district's group method of randomization to be divided into GLA group and matched group (not using GLA) with 2: 1 ratios, the former takes the acemetacin and the glucosamine hydrochloride combined tablet-preparation of embodiment 21 preparation, and the latter removes the identical but placebo of hydrochloric glucosamine not of tablet profile, color, the taste taken with embodiment 21 preparations.1 of two groups of patient one time, 2 times on the one, when feed or one after each meal, totally 12 weeks.Result: GLA organizes effective percentage 88%, matched group 65%, and both have marked difference (P=0.00).Except that the morning deadlock, the GLA group is in the improvement value of other every clinical indices and improve and all be higher than matched group (P＜0.05=on the percentage rate.GLA group rate of side effects is 30%, accounts for overwhelming majority's (80%) with slight untoward reaction.Physiology, psychology, society, healthy self-recognition and overall quality of life improvement value median are respectively 3.5,2.0,3.0,2.0,2.3 before and after the treatment of GLA group, level improves 10%～25% before the treatment, be better than matched group and improve 1%～11% (corresponding improvement value median is 2.0,1.5,1.5,0,2.1, and the P value is respectively 0.01,0.28,0.13,0.005,0.03).Physiological function is divided and overall quality of life divides highly than the low group of curative effect before the high patient of GLA group curative effect, and mental function divides low grouping low, and treatment back quality of life improves also obvious.GLA organizes overall quality of life and improves and divide high patient to organize clinical indices to improve and be better than low grouping.Conclusion: NSAIDs adds with GLA treatment adult activeness quasi-wind gateway patient 3 months, be better than matched group on clinical symptoms is improved, and side reaction is slight.NSAIDs added with GLA treatment adult activeness RA quality of life singly has higher quality of life with the non-steroidal anti-inflammatory analgesics, and especially physiological function is obviously limited before the treatment, and poor life quality and mental function be activeness patient RA preferably.Above-mentioned test has beyond thought good action from the angle proof non-steroidal anti-inflammatory drug associating glucosamine treatment of clinical trial to rheumatoid arthritis, further illustrates the clinical value of composition of medicine of the present invention.
Table 1 liang group patient physical data relatively
| Project | GLA organizes (n=90) | Matched group (n=42) | P |
| Sex (man/woman) age 1)(year) (scope) course of disease 1)(moon) (scope) function of joint classification (II/IIII/IV) | 19/71 46(20～70) 12(1～360) 63/21/7 | 13/29 50(20～72) 12(1～240) 28/13/1 | 0.23 0.73 0.56 0.43 |
Annotate: 1) median
Fig. 1 GLA group and matched group clinical indices improvement value are relatively
MAIN OUTCOME MEASURES improvement value relatively before and after the table 2 liang group Case treatment
| Project | The GLA group1)(interquartile range) | Control group1)(interquartile range) | P |
| Articular pain is counted the arthroncus of articular pain index and is counted joint swelling index grip (kPa) deadlock in morning (branch) ESR CRP RHF | 9.5(-2～35) 19(-1～72) 9(0～32) 16(1～59) 2.66(-4.66～14.10) 100(-60～120) 15.5(-10～90) 55.5(0～287) 176(0～343) | 2(-8～24) 9(-10～40) 3.5(-6～18) 9.5(-10～33) 0.67(-3.99～4.66) 60(-120～100) 7(-14～73) 15(-1～325) 114(-20～249) | 0.001 0.002 0.000 0.002 0.001 0.920 0.050 0.005 0.020 |
Annotate: 1) median
Quality of life branch (median) relatively before the table 3 liang group Case treatment
| Group | The example number | Quality of life before the treatment | ||||
| Physiological function | Mental functioning | Social function | Healthy self-recognition | Overall quality of life | ||
| The GLA group | 90 | 17.5(9～34) | 20(15～29) | 15(8～30) | 20(11～28) | 1.8(0.6～3.4) |
| Control group | 42 | 17(8～31) | 19(15～26) | 13.5(7～27) | 22(13～27) | 1.5(0.5～3.1) |
| The P value | 0.05 | 0.09 | 0.18 | 0.33 | 0.15 | |
Quality of life improvement value (median) relatively after table 4GLA group and the treatment of control group
| Group | The example number | Quality of life before the treatment | ||||
| Physiological function | Mental functioning | Social function | Healthy self-recognition | Overall quality of life | ||
| The GLA group | 90 | 3.5(-5～ 20) | 2.0(-4～ 10) | 3.0(-4～ 16) | 2.0(-5～ 10) | 2.3(1.6～3.4) |
| Control group | 42 | 2.0(-3～ 10) | 1.5(-5～7) | 1.5(-3～8) | 0(-4～6) | 2.1(1.6～2.6) |
| The P value | 0.01 | 0.28 | 0.13 | 0.005 | 0.03 |
Quality of life improvement value relatively after the low patient of table 5 curative effect height and curative effect organized the front quality of life branch for the treatment of and treatment
| Quality of life* | The curative effect height | Curative effect is low | ||||||
| GLA organizes (34 example) | Control group (6 example) | GLA organizes (18 example) | Control group (22 example) | |||||
| Before the treatment** | After the treatment*** | Before the treatment | After the treatment | Before the treatment** | After the treatment*** | Before the treatment | After the treatment | |
| Physiological function | 20(9～ 33) | 6(0～18) | 22.5 | 6 | 16(10～ 22) | 2(-1～ 7) | 12(9～ 17) | 0(-3～6) |
| Mental functioning | 17(13～ 22) | 2(-1～7) | 20 | 3 | 20(17～ 23) | 0(-3～ 4) | 22(1～ 24) | -1(-4～ 4) |
| Social function | 17(9～ 29) | 3(-1～ 15) | 23 | 2.5 | 14(10～ 18) | 0(-3～ 4) | 13(8～ 21) | 0(-3～5) |
| Healthy self-recognition | 21(16～ 26) | 2.5(-1～ 8) | 22 | 3.5 | 20(18～ 21) | 1(-3～ 3) | 19(16～ 23) | 0(-3～5) |
| Overall quality of life | (1.86) (0.7～ 3.3) | (2.42) (1.9～ 3.6) | 2.71 | 2.43 | (1.51) (1.1～ 1.9) | (1.98) (1.6～ 2.6) | (1.45) (0.8～ 1.8) | (1.94) (1.6～ 2.5) |
Annotate:*Be median (interquartile range);**Be the quality of life branch;***Be quality of life improvement value
The high grouping of the overall quality of life improvement value of table 6 and low grouping clinical indices are improved percentage comparisons
| Clinical indices | Quality of life is improved high grouping | Quality of life is improved low grouping | ||
| GLA organizes (30 example) | Control group (10 example) | GLA organizes (22 example) | Control group (18 example) | |
| The articular pain number | 80 | 30 | 50 | 8.3 |
| The articular pain index | 87 | 50 | 67 | 46 |
| The arthroncus number | 87 | 18 | 63 | 23 |
| Joint swelling index | 90 | 40 | 65 | 51 |
| | 50 | 20 | 7.7 | 2.6 |
| Morning deadlock | 88 | 69 | 70 | 65 |
| ESR | 90 | 89 | 38 | 25 |
| CRP | 99 | 79 | 90 | 78 |
| RHF | 89 | 70 | 50 | 15 |
| Comprehensive therapeutic effect | 84 | 60 | 55 | 37 |
NSAIDs part and glucosamine part (by the glucosamine molecule) are formed with certain weight ratio in the composition of medicine of the present invention, dosage form can be oral formulations, injection or ophthalmic preparation, as: peroral dosage forms such as tablet (comprising enteric coatel tablets, slow releasing tablet, controlled release tablet), capsule (comprising enteric coated capsule, slow releasing capsule, controlled release capsule), soft capsule, drop pill, granule, dispersible tablet, powder, oral cavity disintegration tablet, oral solution and syrup, and ophthalmic preparation such as injection such as injection, powder ampoule agent for injection and infusion solution and eye drop.
For further reducing the zest raising curative effect of medicine to stomach, can be made into enteric coated preparation, wherein non_steroidal anti_inflammatory drug partly is all the enteric part separately or with glucosamine, after the oral administration administration, discharges at intestinal; Also can make sustained-release preparation, non_steroidal anti_inflammatory drug wherein partly is all slow controlled release part separately or with glucosamine, after the oral administration administration, slowly discharges, slow constant release or slowly near constant release.
Two-part proportion of composing is in the combined pharmaceutical formulation of determining: each sheet, grain, or other each unit formulation in, the amount of glucosamine part (by the glucosamine molecule) is 50mg～1000mg, and the amount of nonsteroidal anti-inflammatory analgetic (NSAIDs) part is respectively: ibuprofen 25mg～500mg, naproxen 25mg～750mg, oxaprozin 50mg～500mg, fenoprofen calcium 100mg～1000mg, flurbiprofen 25mg～250mg, loxoprofen (loxoprofen sodium) 25mg～200mg, pranoprofen 25mg～250mg, diclofenac sodium (potassium) 10mg～300mg, lornoxicam 1mg～25mg, etodolac 50mg～500mg, clofenamic acid 50mg～500mg, piroxicam 3mg～100mg, indomethacin 5.5mg～150mg, acemetacin 7.5mg～150mg, nabumetone 50mg～1500mg, sulindac 50mg～500mg, diclofenac sodium (or diclofenac potassium) 10mg～150mg, ketorolac trometamol 2mg～50mg, meloxicam 2mg～25mg or celecoxib 50mg～800mg.
Preferred proportion is: the amount of glucosamine part (by the glucosamine molecule) is 50mg～750mg, and the amount of nonsteroidal anti-inflammatory analgetic (NSAIDs) part is respectively: and ibuprofen 50mg～250mg (250mg in the sustained-release preparation～400mg), naproxen 50mg～500mg (250mg in the sustained-release preparation～500mg), oxaprozin 150mg～300mg (150mg in the sustained-release preparation～400mg), fenoprofen calcium 150mg～600mg (200mg in the sustained-release preparation～800mg), flurbiprofen 50mg～200mg (50mg in the sustained-release preparation～300mg), loxoprofen 25mg～150mg (25mg in the sustained-release preparation～300mg), pranoprofen 25mg～125mg (25mg in the sustained-release preparation～250mg), diclofenac sodium (potassium) 10mg～100mg (50mg in the sustained-release preparation～300mg), lornoxicam 2mg～10mg (2mg in the sustained-release preparation～20mg), etodolac 100mg～500mg (200mg in the sustained-release preparation～500mg), clofenamic acid 100mg～300mg (100mg in the sustained-release preparation～400mg), piroxicam 5mg～60mg (10mg in the sustained-release preparation～100mg), indomethacin 5.5mg～90mg (25mg in the sustained-release preparation～120mg), acemetacin 7.5mg～100mg (25mg in the sustained-release preparation～120mg), nabumetone 100mg～750mg (200mg in the sustained-release preparation～1000mg), sulindac 50mg～300mg (150mg in the sustained-release preparation～500mg), diclofenac sodium (potassium) 10mg～100mg (25mg in the sustained-release preparation～100mg), ketorolac trometamol 5mg～25mg (5mg in the sustained-release preparation～90mg), meloxicam 5mg～20mg (5mg in the sustained-release preparation～25mg) or celecoxib 50mg～500mg (100mg in the sustained-release preparation～800mg).
When the present invention prepared infusion solution, the isoosmotic adjusting agent of adding can be sodium chloride, potassium chloride, sodium lactate, xylitol, sorbitol, maltose, glucose, fructose, dextran or glycine etc.Add additives in the injection and can be stabilizing agent on the pharmaceutics such as antioxidant, complexing of metal ion agent, acidity-basicity regulator etc., antioxidant can be that in sodium pyrosulfite (0.1% ~ 0.2%), sodium sulfite (0.1% ~ 0.2%), sodium thiosulfate (0.1%), the vitamin C (0.2%) etc. one or more are united use; The complexing of metal ion agent can be EDTA disodium, EDTA calcium sodium or the two use in conjunction; Acidity-basicity regulator can be that one or more mixing in the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution and hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid and each seed amino acid are used, and is 5.5 ~ 7.5 with the pH value of regulating transfusion.
When the present invention prepares dosage forms such as tablet, capsule, soft capsule, drop pill, granule, dispersible tablet, powder, oral solution, syrup, eye drop, injection, transfusion and injectable powder, what adopt is the prior art and the equipment of these dosage forms of preparation, need not specific (special) requirements, be suitable for large-scale production, so be easy to promote.
Below be several typical embodiment among the present invention, do not contain full content and claim scope:
The specific embodiment
Embodiment 1: preparation tablets
| Indomethacin N-acetylglucosamine lactose starch | 25g 75g 10g 5.0g |
| Carboxymethyl starch |
2.7g 0.9g is an amount of |
| Make | 1000 |
Preparation technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting.
Embodiment 2: the capsule preparation
| Acemetacin glucosamine sulfate pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 25g 500g 12g 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 3: the dispersible tablet preparation
| Supplementary material acemetacin 2-Acetamido-2-deoxy-D-glucose |
Consumption 25g 75g (by Glucosamine) 25.0g 150ml 10.0g 2.0g 2.0g 2.6g 10.0g |
| Make | 1000 |
Technology: take by weighing polyvinylpyrrolidone by recipe quantity, make 10% solution (1) with 80% ethanol; Take by weighing cross-linking sodium carboxymethyl cellulose, aspartame, micropowder silica gel and the magnesium stearate mix homogeneously (2) of crossing 100 mesh sieves respectively by prescription; Take by weighing acemetacin, N-acetylglucosamine, mannitol and crospolyvinylpyrrolidone, the mixing of crossing 100 mesh sieves by recipe quantity, cross 80 mesh sieves twice, add (1), 18 mesh sieves are granulated, 60 ± 5 ℃ of oven dry, 20 mesh sieve granulate; Add (2) fully mixing; Tabletting; After the assay was approved, packing.
Embodiment 4: the Film coated tablets preparation
| Acemetacin N-acetylglucosamine dimethoxym ethane lactose starch | 25g 300g (by glucosamine) 10g 3.0g |
| Carboxymethyl starch |
3g 0.9g 10ml |
| Make | 1000 |
Technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting, (7) substrate Opadry coating solution bag film-coat.
Embodiment 5: the enteric coated capsule preparation
| Naproxen glucosamine hydrochloride pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 125g 150g 12g 25g 1％ |
| Make | 1000 |
Preparation technology: each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; In the dress enteric capsule shell.
Embodiment 6: the capsule preparation
| Oxaprozin chondroitin sulfate pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 150g 500g 12g 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 7: preparation tablets
| Brufen Glucosamine sulfate potassium chloride L-HPC microcrystalline cellulose PVP K30 lauryl sodium sulfate magnesium stearate ethanol | 125g 100g (by Glucosamine) 14g 11.2g 3.9g 1.4g 0.84g is an amount of |
| Make | 1000 |
Preparation technology: 1. take by weighing ibuprofen, Glucosamine Sulfate Potassium salt, hyprolose, microcrystalline Cellulose, mix homogeneously.2. pulverize, once more mix homogeneously.3. make suitable soft material with 10% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution.4. 14 order nylon wires are granulated.5. rapid draing below 60 ℃.6. add sodium lauryl sulphate, magnesium stearate, mix homogeneously.7. 12 order nylon wire granulate.8. use the flat stamping of Ф 8mm, the heavy 0.28g of control strip.9. pack after the assay was approved.
Embodiment 8: the granule preparation
| Nabumetone | 150g 250g (by glucosamine) 30g is an amount of |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. acemetacin, glucosamine sulfate are pulverized, and cross 80 mesh sieves.3. take by weighing guacetisal and cane sugar powder, mix homogeneously.4. make suitable soft material with 10% starch slurry.5. 12 order nylon wires are granulated.6. granule is in rapid draing below 50-60 ℃, and control moisture is below 1%.7. use 12 order nylon wire granulate.8. add spice, mix homogeneously.9. after the assay was approved, pack, packing.
Embodiment 9: the preparation of dry suspension
| Meloxicam N-acetylglucosamine hyprolose xanthan gum spice cane sugar powder | 12.5g 150g (by glucosamine) 36g 30g 30g 2404g |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. accurately take by weighing each supplementary material.3. above-mentioned mixing of materials is pulverized, and crosses 80 mesh sieves.4. material mixes once more, sample examination.5. pack, pack.
Embodiment 10: the preparation of slow releasing capsule
Ball core prescription:
| Acemetacin glucosamine hydrochloride celphere 90% ethanol | 90g 200g (by glucosamine) 262.5g is an amount of |
The coating prescription:
| Eudragit RS EC 95% ethanol | 42g 42g is an amount of |
| Make | 1000 |
Preparation technology: acemetacin, PVPK30 are dissolved in 90% ethanol, wind pressure 0.7bar is gone in start, pours the ball core of recipe quantity in the pot into, spray principal agent, PVPK30 mixed solution, CAPL is 1.0bar, and CYL is 2.3bar, and rotating speed is 145rpm, the revolution speed 10% of wriggling, SV48 ℃ of inlet air temperature, PV48 ℃, product temperature SV19 ℃, PV22 ℃, 60 ℃ of oven dry.
Eudragit RS and EC are dissolved in 95% ethanol, are made into coating solution, start, go into wind pressure 0.7bar, pour above-mentioned ball core in the pot, the spray coating solution, CAPL is 0.9bar, CYL is 2.3bar, rotating speed is 150rpm, the revolution speed 6% of wriggling, SV29 ℃ of inlet air temperature, PV29 ℃, product temperature SV19 ℃, PV22 ℃, 40 ℃ of oven dry.Add glucosamine hydrochloride, magnesium stearate, mixing detects intermediate, determines loading amount, the dress capsule.
Embodiment 11: the preparation of slow releasing tablet
The label prescription:
| Acemetacin Glucosamine Sulphate polyvinylpyrrolidone stearic acid brazil wax microcrystalline cellulose | 60g 200g (by Glucosamine) 20g 20g 70g 40g 20g an amount of 0.5% | |
| Make | 1000 | |
Coating fluid prescription:
| | 3.2g add to 40 milliliters |
Preparation technology: acemetacin, glucosamine sulfate, microcrystalline Cellulose, calcium hydrogen phosphate and polyvinylpyrrolidone are crossed 80 mesh sieves, and stearic acid, brazil wax are crossed 60 mesh sieves.Take by weighing above-mentioned adjuvant by recipe quantity, mix homogeneously adds the principal agent of recipe quantity with the equivalent method of progressively increasing, mixing, and guiding humid medium system soft material, 20 mesh sieves are granulated, 50 ℃ of dryings, 20 mesh sieve granulate, the magnesium stearate of adding recipe quantity in dried granule, mixing, tabletting, coating.
Embodiment 12: the preparation of controlled release tablet
A slow-released part prescription is formed:
| Acemetacin Hydroxypropyl methylcellulose (100000CPS) microcrystalline cellulose ethyl cellulose (10CPS) material) dolomol B immediate release section acemetacin Glucosamine Sulphate lactose microcrystal carboxymethyl cellulose Starch Sodium 0.5% Hydroxypropyl methylcellulose (5CPS) dolomol | 70g (main ingredient) 160g (slow-release material) 15g (adjusting pellet hardness) 7.5g (an amount of (adhesive) 0.9g (lubricant) of adhesive and insoluble slowly-releasing material 3g (lubricant) 5g (main ingredient) 250g (main ingredient) 40g (filler) 29.5g (filler) 15g (disintegrant) |
| Make | 1000 |
Technology: (1) crosses acemetacin 80 mesh sieves respectively, and glucosamine sulfate is crossed 100 mesh sieves, and it is standby that lactose is crossed 80 mesh sieves.(2) ethyl cellulose of recipe quantity is standby with an amount of wiring solution-forming of dehydrated alcohol; Molten 0.5% aqueous solution that is made into of hypromellose (5CPS) is standby.(3) acemetacin is mixed with hypromellose and microcrystalline Cellulose, the adding ethyl cellulose solution stirs and makes soft material, crosses 16 mesh sieves and makes wet grain, at 60 ℃ of dry dry granular P1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular P2, measure the content of acemetacin among the dry granular P2, it is heavy to calculate sheet.(4) acemetacin (immediate release section), glucosamine sulfate and lactose are mixed by the equivalent mixing method of progressively increasing, adding microcrystalline Cellulose and carboxymethylstach sodium again mixes, the hypromellose solution of adding 0.5% is an amount of, soft material is made in stirring, the soft material that makes is crossed 16 mesh sieves granulate, at 60 ℃ of dry dry granular C1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular C2, measure the content of acemetacin and glucosamine sulfate among the dry granular C2, it is heavy to calculate sheet.(5) dry granular P2 and dry granular C2 are put tabletting on the bi-layer tablet press, obtain semi-finished product.The above-mentioned tablet that makes is carried out quality inspection, and qualified back packing gets product.
The preparation of embodiment 13. syrups
| Supplementary material loxoprofen Glucosamine Sulphate Sodium Benzoate citric acid 95% ethanol grapefruit essence sucrose purified water | Consumption 25g 300g 2.5g 0.3g 5ml 1ml 650g adds to 1000ml |
| Full dose | 1000ml. |
Preparation technology: get the recipe quantity supplementary material, add total amount 3/5 purified water, heating makes is dissolved into syrup, when being cooled to 60 ℃, above-mentioned solution is added, with adding, when being cooled to below 40 ℃, add benzoic acid solution, citric acid soln and Citrua paradiai essence with stirring, add purified water to full dose, stir, filter, promptly.Take 10ml at every turn.
Embodiment 14: the oral administration solution preparation
| Piroxicam aminoglucose hydrochloride propane diols glycerine sorbierite asccharin sodium propionic acid acetic acid-sodium-acetate buffer distilled water | 15g 300g 1500ml 2500g 2500g 1.0g 10ml 1600ml is an amount of |
| Full dose | 10000ml (1000). |
Preparation technology: get an amount of distilled water, add sorbitol earlier, heating makes dissolving, and is cold slightly, adds other adjuvant and crude drug, stirs and makes dissolving, and adding distil water is to full dose.Filter with the G4 sintered glass funnel.The filling machine fill is jumped a queue and is rolled lid, sterilizes 30 minutes for 115.5 ℃, examines qualified back packing entirely, promptly.
Embodiment 15: the drop pill preparation
| Acemetacin glucosamine sulfate sodium stearate insect wax water | 25g 300g 100g 25g 40g |
Each supplementary material beyond dewatering is added in flask, shakes up, shake up again after adding water, will fill in flask with the rubber closure of reflux condensing tube after, jolting constantly also is heated to about 100 ℃ and makes whole fusions, a glue ball.Be coolant with 2% aqueous sulfuric acid when dripping system.Ooze by the dropper mouth when making medicinal liquid remain on 65 ℃.Because this ball proportion is less than 2% aqueous sulfuric acid, for this reason, during drop pill, melt liquid is splashed in the coolant by the bottom of coolant, and every dropper per minute oozes 200 drop pill approximately.Ball is oozed by the drip place and floats, the cooling of limit rising edge, and drop pill can be pulled out with strainer, is dipped in the acid solution of removing attachment removal in the cold water, inserts in the dish of absorbent paper again, makes rolling, after the water mark on pill surface is removed in suction, promptly.
Embodiment 16: the drop pill preparation
| Etodolac glucosamine sulfate polyethylene glycol 6000 | 25g 300g 90g |
Taking polyethylene glycol 6000 is heated to 135 ℃ in oil bath.Add acemetacin, glucosamine sulfate, constantly be stirred to moltenly entirely, (135 ℃) filter while hot, put in the liquid containing bottle, drip system when making it remain on 135 ℃.The drip internal diameter 9.0mm of rustless steel dropper, external diameter 9.8mm.Drip in the outside with the speed of 80 of per minutes and to form drop pill in the refrigerative liquid paraffin condensed fluid that contains 43% kerosene with frozen water.Ball is taken out the back wash several with flush away kerosene flavor, inhale with writing paper made from bamboo and remove adherent liquid paraffin with liquid paraffin.
Embodiment 17: soft capsule preparation
| Acemetacin N-acetylglucosamine PEG400 | 25g 300g (by glucosamine) 400g |
| Make | 1000 |
Two kinds of principal agents with recipe quantity mix with the PEG400 of 1/6 amount earlier, pulverize with colloid mill, add the PEG400 miscible (also available ball mill grinding 3 hours) of surplus then.It is standby that other joins gelatin solution (100 parts in gelatin, 55 parts of glycerol, 120 parts in water).Under the condition of 28 ± 2 ℃ of room temperatures, relative humidity 40%, medicinal liquid and gelatin press capsule machine-processed with rotation automatically, 28 ± 2 ℃, during relative humidity 40% with dry 20 hours of capsule, get product.
Embodiment 18. injectable powder preparation methoies
Prescription: (in 1000)
| Flurbiprofen glucosamine sulfate glycine anhydrous sodium sulfite disodium edetate water for injection | 30g 100g 400g 40g 4g adds to 2000ml |
| Make | 1000 |
Each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5 ~ 7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, determine canned amount according to content, be sub-packed in the antibiotic glass bottle that half tamponade is put into freeze drying box and carried out lyophilizing, the lyophilizing program is cooled to 0 ℃, freezing 5h for shelf in freeze drying box; Shelf is cooled to-45 ℃ gradually, and freezing 6h starts vacuum pump, closes fridge; Shelf is warming up to-20 ℃ gradually, and evacuation 21h is warming up to 10 ℃ gradually continuously, continuous evacuation 5h, gland outlet.Full inspection, packing, warehouse-in.
Embodiment 19: the aqueous injection preparation method
Prescription: (in 1000)
| Diclofenac sodium glucosamine sulfate glycine anhydrous sodium sulfite disodium edetate water for injection | 25g 75g 1.2kg 90g 10g adds to 5000ml |
| Make | 1000 |
Preparation technology: each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5～7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, fill, every 5ml.
Embodiment 20: the infusion solution preparation method
| Ketorolac trometamol hydrochloric acid glucosamine glycine | 12.5g 75g 1.2kg |
| Anhydrous sodium sulfite calcium disodium edetate glucose injection water | 90g 10g 2500g adds to 50000ml |
| Make | 1000 bottles |
Each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5～7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, fill in 50 milliliters of infusion bottles, 115 ℃ of pressure sterilizings 30 minutes.Labeling is packed after the assay was approved.
Embodiment 21: preparation tablets
| Acemetacin aminoglucose hydrochloride lactose starch sodium | 25g 75g 10g 5.0g 2.7g 0.9g is an amount of |
| Make | 1000 |
Preparation technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting.
Embodiment 22: the Film coated tablets preparation
| Indomethacin 2-Acetamido-2-deoxy-D-glucose dimethoxym ethane lactose starch sodium | 25g 300g (by glucosamine) 10g 3.0g 3g 0.9g 10ml |
| Make | 1000 |
Technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting, (7) substrate Opadry coating solution bag film-coat.
Embodiment 23: the dispersible tablet preparation
| Supplementary material Indomethacin 2-Acetamido-2-deoxy-D-glucose sweet | Consumption 25g 75g (by Glucosamine) 25.0g 150ml 10.0g 2.0g 2.0g 2.6g 10.0g |
| Make | 1000 |
Technology: take by weighing polyvinylpyrrolidone by recipe quantity, make 10% solution (1) with 80% ethanol; Take by weighing cross-linking sodium carboxymethyl cellulose, aspartame, micropowder silica gel and the magnesium stearate mix homogeneously (2) of crossing 100 mesh sieves respectively by prescription; Take by weighing indomethacin, N-acetylglucosamine, mannitol and crospolyvinylpyrrolidone, the mixing of crossing 100 mesh sieves by recipe quantity, cross 80 mesh sieves twice, add (1), 18 mesh sieves are granulated, 60 ± 5 ℃ of oven dry, 20 mesh sieve granulate; Add (2) fully mixing; Tabletting; After the assay was approved, packing.
Embodiment 24: the capsule preparation
| The indomethacin glucosamine sulfate | 25g 500g |
| Pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 12g 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 25: the enteric coated capsule preparation
| Indomethacin Glucosamine Sulfate Potassium salt pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 30g 150g 12g 25g 1％ |
| Make | 1000 |
Preparation technology: each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; In the dress enteric capsule shell.
Embodiment 26: the capsule preparation
| The pregelatinized Starch of indomethacin chondroitin sulfate | 25g 500g 12g |
| Microcrystalline Cellulose 2%HPMC (50cp) | 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 27: preparation tablets
| Indomethacin Glucosamine sulfate sodium chloride L-HPC microcrystalline cellulose PVP K30 lauryl sodium sulfate magnesium stearate ethanol | 25g 100g (by Glucosamine) 14g 11.2g 3.9g 1.4g 0.84g is an amount of |
| Make | 1000 |
Preparation technology: 1. take by weighing indomethacin, Glucosamine Sulfate Potassium salt, hyprolose, microcrystalline Cellulose, mix homogeneously.2. pulverize, once more mix homogeneously.3. make suitable soft material with 10% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution.4. 14 order nylon wires are granulated.5. rapid draing below 60 ℃.6. add sodium lauryl sulphate, magnesium stearate, mix homogeneously.7. 12 order nylon wire granulate.8. use the flat stamping of Ф 8mm, the heavy 0.28g of control strip.9. pack after the assay was approved.
Embodiment 28: the granule preparation
| |
12.5g 250g (by glucosamine) 30g is an amount of |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. indomethacin, chitin are pulverized, and cross 80 mesh sieves.3. take by weighing guacetisal and cane sugar powder, mix homogeneously.4. make suitable soft material with 10% starch slurry.5. 12 order nylon wires are granulated.6. granule is in rapid draing below 50-60 ℃, and control moisture is below 1%.7. use 12 order nylon wire granulate.8. add spice, mix homogeneously.9. after the assay was approved, pack, packing.
Embodiment 29: the preparation of dry suspension
| Indomethacin N-acetylglucosamine hyprolose xanthan gum spice cane sugar powder | 12.5g 150g (by glucosamine) 36g 30g 30g 2404g |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. accurately take by weighing each supplementary material.3. above-mentioned mixing of materials is pulverized, and crosses 80 mesh sieves.4. material mixes once more, sample examination.5. pack, pack.
Embodiment 30: the preparation of slow releasing capsule
Ball core prescription:
| Indomethacin hydrochloric acid Glucosamine blank pill core 90% ethanol dressing prescription: Eudragit RS EC 95% ethanol | An amount of 42g 42g of 90g 200g (by Glucosamine) 262.5g is an amount of |
| Make | 1000 |
Preparation technology: indomethacin, PVPK30 are dissolved in 90% ethanol, wind pressure 0.7bar is gone in start, pours the ball core of recipe quantity in the pot into, spray principal agent, PVPK30 mixed solution, CAPL is 1.0bar, and CYL is 2.3bar, and rotating speed is 145rpm, the revolution speed 10% of wriggling, SV48 ℃ of inlet air temperature, PV48 ℃, product temperature SV19 ℃, PV22 ℃, 60 ℃ of oven dry.
Eudragit RS and EC are dissolved in 95% ethanol, are made into coating solution, start, go into wind pressure 0.7bar, pour above-mentioned ball core in the pot, the spray coating solution, CAPL is 0.9bar, CYL is 2.3bar, rotating speed is 150rpm, the revolution speed 6% of wriggling, SV29 ℃ of inlet air temperature, PV29 ℃, product temperature SV19 ℃, PV22 ℃, 40 ℃ of oven dry.Add glucosamine hydrochloride, magnesium stearate, mixing detects intermediate, determines loading amount, the dress capsule.
Embodiment 31: the preparation of slow releasing tablet
The label prescription:
| Indomethacin | 60g |
| Glucosamine Sulphate polyvinylpyrrolidone stearic acid brazil wax microcrystalline cellulose |
200g (by Glucosamine) 20g 20g 70g 40g 20g an amount of 0.5% | |
| Make | 1000 | |
Coating fluid prescription:
| | 3.2g add to 40 milliliters |
Preparation technology: indomethacin, glucosamine sulfate, microcrystalline Cellulose, calcium hydrogen phosphate and polyvinylpyrrolidone are crossed 80 mesh sieves, and stearic acid, brazil wax are crossed 60 mesh sieves.Take by weighing above-mentioned adjuvant by recipe quantity, mix homogeneously adds the principal agent of recipe quantity with the equivalent method of progressively increasing, mixing, and guiding humid medium system soft material, 20 mesh sieves are granulated, 50 ℃ of dryings, 20 mesh sieve granulate, the magnesium stearate of adding recipe quantity in dried granule, mixing, tabletting, coating.
Embodiment 32: the preparation of controlled release tablet
A slow-released part prescription is formed:
| Indomethacin hypromellose (100000CPS) microcrystalline Cellulose | 70g (principal agent) 160g (slow-release material) 15g (adjusting pellet hardness) |
| Ethyl cellulose (10CPS) material) dolomol B immediate release section Indomethacin Glucosamine Sulphate lactose microcrystal carboxymethyl cellulose Starch Sodium 0.5% Hydroxypropyl methylcellulose (5CPS) dolomol | 7.5g (an amount of (adhesive) 0.9g (lubricant) of adhesive and insoluble slowly-releasing material 3g (lubricant) 5g (main ingredient) 250g (main ingredient) 40g (filler) 29.5g (filler) 15g (disintegrant) |
| Make | 1000 |
Technology: (1) crosses indomethacin 80 mesh sieves respectively, and glucosamine sulfate is crossed 100 mesh sieves, and it is standby that lactose is crossed 80 mesh sieves.(2) ethyl cellulose of recipe quantity is standby with an amount of wiring solution-forming of dehydrated alcohol; Molten 0.5% aqueous solution that is made into of hypromellose (5CPS) is standby.(3) indomethacin is mixed with hypromellose and microcrystalline Cellulose, the adding ethyl cellulose solution stirs and makes soft material, crosses 16 mesh sieves and makes wet grain, at 60 ℃ of dry dry granular P1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular P2, measure the content of indomethacin among the dry granular P2, it is heavy to calculate sheet.(4) indomethacin (immediate release section), glucosamine sulfate and lactose are mixed by the equivalent mixing method of progressively increasing, adding microcrystalline Cellulose and carboxymethylstach sodium again mixes, the hypromellose solution of adding 0.5% is an amount of, soft material is made in stirring, the soft material that makes is crossed 16 mesh sieves granulate, at 60 ℃ of dry dry granular C1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular C2, measure the content of indomethacin and glucosamine sulfate among the dry granular C2, it is heavy to calculate sheet.(5) dry granular P2 and dry granular C2 are put tabletting on the bi-layer tablet press, obtain semi-finished product.The above-mentioned tablet that makes is carried out quality inspection, and qualified back packing gets product.
The preparation of embodiment 33. syrups
| Supplementary material Indomethacin Glucosamine Sulphate Sodium Benzoate citric acid 95% ethanol grapefruit essence sucrose purified water | Consumption 25g 300g 2.5g 0.3g 5ml 1ml 650g adds to 1000ml |
| Full dose | 1000ml. |
Preparation technology: get the recipe quantity supplementary material, add total amount 3/5 purified water, heating makes is dissolved into syrup, when being cooled to 60 ℃, above-mentioned solution is added, with adding, when being cooled to below 40 ℃, add benzoic acid solution, citric acid soln and Citrua paradiai essence with stirring, add purified water to full dose, stir, filter, promptly.Take 10ml at every turn.
Embodiment 34: the oral administration solution preparation
| Indomethacin glucosamine hydrochloride propylene glycol | 25g 300g 1500ml |
| Glycerol sorbitol glucide sodium propanoic acid acetic acid-sodium-acetate buffer distilled water | 2500g 2500g 1.0g 10ml 1600ml is an amount of |
| Full dose | 10000ml (1000). |
Technology: get an amount of distilled water, add sorbitol earlier, heating makes dissolving, and is cold slightly, adds other adjuvant and crude drug, stirs and makes dissolving, and adding distil water is to full dose.Filter with the G4 sintered glass funnel.The filling machine fill is jumped a queue and is rolled lid, sterilizes 30 minutes for 115.5 ℃, examines qualified back packing entirely, promptly.
Embodiment 35: the drop pill preparation
| Indomethacin glucosamine sulfate sodium stearate insect wax water | 25g 300g 100g 25g 40g |
Each supplementary material beyond dewatering is added in flask, shakes up, shake up again after adding water, will fill in flask with the rubber closure of reflux condensing tube after, jolting constantly also is heated to about 100 ℃ and makes whole fusions, a glue ball.Be coolant with 2% aqueous sulfuric acid when dripping system.Ooze by the dropper mouth when making medicinal liquid remain on 65 ℃.Because this ball proportion is less than 2% aqueous sulfuric acid, for this reason, during drop pill, melt liquid is splashed in the coolant by the bottom of coolant, and every dropper per minute oozes 200 drop pill approximately.Ball is oozed by the drip place and floats, the cooling of limit rising edge, and drop pill can be pulled out with strainer, is dipped in the acid solution of removing attachment removal in the cold water, inserts in the dish of absorbent paper again, makes rolling, after the water mark on pill surface is removed in suction, promptly.
Embodiment 36: the drop pill preparation
| Indomethacin glucosamine sulfate polyethylene glycol 6000 | 25g 300g 90g |
Taking polyethylene glycol 6000 is heated to 135 ℃ in oil bath.Add indomethacin, glucosamine sulfate, constantly be stirred to moltenly entirely, (135 ℃) filter while hot, put in the liquid containing bottle, drip system when making it remain on 135 ℃.The drip internal diameter 9.0mm of rustless steel dropper, external diameter 9.8mm.Drip in the outside with the speed of 80 of per minutes and to form drop pill in the refrigerative liquid paraffin condensed fluid that contains 43% kerosene with frozen water.Ball is taken out the back wash several with flush away kerosene flavor, inhale with writing paper made from bamboo and remove adherent liquid paraffin with liquid paraffin.
Embodiment 37: soft capsule preparation
| Indomethacin N-acetylglucosamine PEG400 | 25g 300g (by glucosamine) 400g |
| Make | 1000 |
Two kinds of principal agents with recipe quantity mix with the PEG400 of 1/6 amount earlier, pulverize with colloid mill, add the PEG400 miscible (also available ball mill grinding 3 hours) of surplus then.It is standby that other joins gelatin solution (100 parts in gelatin, 55 parts of glycerol, 120 parts in water).Under the condition of 28 ± 2 ℃ of room temperatures, relative humidity 40%, medicinal liquid and gelatin press capsule machine-processed with rotation automatically, 28 ± 2 ℃, during relative humidity 40% with dry 20 hours of capsule, get product.
Embodiment 38. injectable powder preparation methoies
Prescription: (in 1000)
| Indomethacin glucosamine sulfate glycine anhydrous sodium sulfite disodium edetate water for injection | 12.5g 100g 400g 40g 4g adds to 2000ml |
| Make | 1000 |
Each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5 ~ 7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, determine canned amount according to content, be sub-packed in the antibiotic glass bottle that half tamponade is put into freeze drying box and carried out lyophilizing, the lyophilizing program is cooled to 0 ℃, freezing 5h for shelf in freeze drying box; Shelf is cooled to-45 ℃ gradually, and freezing 6h starts vacuum pump, closes fridge; Shelf is warming up to-20 ℃ gradually, and evacuation 21h is warming up to 10 ℃ gradually continuously, continuous evacuation 5h, gland outlet.Full inspection, packing, warehouse-in.
Embodiment 39: the aqueous injection preparation method
Prescription: (in 1000)
| Indomethacin glucosamine sulfate glycine anhydrous sodium sulfite disodium edetate water for injection | 12.5g 75g 1.2kg 90g 10g adds to 5000ml |
| Make | 1000 |
Preparation technology: each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5～7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, fill, every 5ml.
Embodiment 40: the infusion solution preparation method
| Indomethacin hydrochloric acid Glucosamine glycine anhydrous sodium sulfite mosatil glucose injection water | 12.5g 75g 1.2kg 90g 10g 2500g adds to 50000ml |
| Make | 1000 bottles |
Each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5～7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, fill in 50 milliliters of infusion bottles, 115 ℃ of pressure sterilizings 30 minutes.Labeling is packed after the assay was approved.
Embodiment 41: the eye drop preparation method
| Indomethacin glucosamine hydrochloride boric acid Borax water for injection | 40g 75g 80.98g 23.5g adds to 8000ml |
| Make | 1000 |
Take by weighing the boric acid of recipe quantity and Borax in the dosing cylinder, add 6000ml water for injection, heating, stirring make whole dissolvings, the indomethacin and the glucosamine hydrochloride that add recipe quantity continued heated and boiled 5-15 minute, put cold, filter with No. 6 sintered glass funnels or micropore filter (filter membrane 0.22 μ m), add to the full amount of water for injection packing, 115 ℃ of pressure sterilizings 30 minutes.Promptly.
Embodiment 42: the capsule preparation
| Diclofenac sodium (potassium) glucosamine sulfate | 25g 500g |
| Pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 12g 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 43: the dispersible tablet preparation
| Supplementary material C14H10Cl2NNaO2 (potassium) 2-Acetamido-2-deoxy-D-glucose sweet | Consumption 25g 75g (by Glucosamine) 25.0g 150ml 10.0g 2.0g 2.0g 2.6g 10.0g |
| Make | 1000 |
Technology: take by weighing polyvinylpyrrolidone by recipe quantity, make 10% solution (1) with 80% ethanol; Take by weighing cross-linking sodium carboxymethyl cellulose, aspartame, micropowder silica gel and the magnesium stearate mix homogeneously (2) of crossing 100 mesh sieves respectively by prescription; Take by weighing diclofenac sodium (potassium), N-acetylglucosamine, mannitol and crospolyvinylpyrrolidone, the mixing of crossing 100 mesh sieves by recipe quantity, cross 80 mesh sieves twice, add (1), 18 mesh sieves are granulated, 60 ± 5 ℃ of oven dry, 20 mesh sieve granulate; Add (2) fully mixing; Tabletting; After the assay was approved, packing.
Embodiment 44: the Film coated tablets preparation
| C14H10Cl2NNaO2 (potassium) 2-Acetamido-2-deoxy-D-glucose dimethoxym ethane lactose starch sodium | 25g 300g (by glucosamine) 10g 3.0g 3g 0.9g 10ml |
| Make | 1000 |
Technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting, (7) substrate Opadry coating solution bag film-coat.
Embodiment 45: the enteric coated capsule preparation
| Diclofenac sodium (potassium) glucosamine hydrochloride pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 30g 150g 12g 25g 1％ |
| Make | 1000 |
Preparation technology: each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; In the dress enteric capsule shell.
Embodiment 46: the capsule preparation
| Diclofenac sodium (potassium) chondroitin sulfate pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 25g 500g 12g 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 47: preparation tablets
| Diclofenac sodium (potassium) | 25g |
| Glucosamine sulfate potassium chloride L-HPC microcrystalline cellulose PVP K30 lauryl sodium sulfate magnesium stearate ethanol | 100g (by glucosamine) 14g 11.2g 3.9g 1.4g 0.84g is an amount of |
| Make | 1000 |
Preparation technology: 1. take by weighing diclofenac sodium (potassium), Glucosamine Sulfate Potassium salt, hyprolose, microcrystalline Cellulose, mix homogeneously.2. pulverize, once more mix homogeneously.3. make suitable soft material with 10% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution.4. 14 order nylon wires are granulated.5. rapid draing below 60 ℃.6. add sodium lauryl sulphate, magnesium stearate, mix homogeneously.7. 12 order nylon wire granulate.8. use the flat stamping of Ф 8mm, the heavy 0.28g of control strip.9. pack after the assay was approved.
Embodiment 48: the granule preparation
| Diclofenac sodium (potassium) | 12.5g 250g (by glucosamine) 30g is an amount of |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. diclofenac sodium (potassium), chitin are pulverized, and cross 80 mesh sieves.3. take by weighing guacetisal and cane sugar powder, mix homogeneously.4. make suitable soft material with 10% starch slurry.5. 12 order nylon wires are granulated.6. granule is in rapid draing below 50-60 ℃, and control moisture is below 1%.7. use 12 order nylon wire granulate.8. add spice, mix homogeneously.9. after the assay was approved, pack, packing.
Embodiment 49: the preparation of dry suspension
| Diclofenac sodium (potassium) N-acetylglucosamine hyprolose xanthan gum spice cane sugar powder | 12.5g 150g (by glucosamine) 36g 30g 30g 2404g |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. accurately take by weighing each supplementary material.3. above-mentioned mixing of materials is pulverized, and crosses 80 mesh sieves.4. material mixes once more, sample examination.5. pack, pack.
Embodiment 50: the preparation of slow releasing capsule
Ball core prescription:
| Diclofenac sodium (potassium) glucosamine hydrochloride celphere 90% ethanol | 90g 200g (by glucosamine) 262.5g is an amount of |
The coating prescription:
| Eudragit RS EC | 42g 42g |
| 95% ethanol | In right amount |
| Make | 1000 |
Preparation technology: diclofenac sodium (potassium), PVPK30 are dissolved in 90% ethanol, wind pressure 0.7bar is gone in start, pours the ball core of recipe quantity in the pot into, spray principal agent, PVPK30 mixed solution, CAPL is 1.0bar, and CYL is 2.3bar, and rotating speed is 145rpm, the revolution speed 10% of wriggling, SV48 ℃ of inlet air temperature, PV48 ℃, product temperature SV19 ℃, PV22 ℃, 60 ℃ of oven dry.
Eudragit RS and EC are dissolved in 95% ethanol, are made into coating solution, start, go into wind pressure 0.7bar, pour above-mentioned ball core in the pot, the spray coating solution, CAPL is 0.9bar, CYL is 2.3bar, rotating speed is 150rpm, the revolution speed 6% of wriggling, SV29 ℃ of inlet air temperature, PV29 ℃, product temperature SV19 ℃, PV22 ℃, 40 ℃ of oven dry.Add glucosamine hydrochloride, magnesium stearate, mixing detects intermediate, determines loading amount, the dress capsule.
Embodiment 51: the preparation of slow releasing tablet
The label prescription:
| C14H10Cl2NNaO2 (potassium) Glucosamine Sulphate polyvinylpyrrolidone stearic acid brazil wax microcrystalline cellulose | 60g 200g (by Glucosamine) 20g 20g 70g 40g 20g is an amount of |
| Magnesium stearate | 0.5％ |
| Make | 1000 |
Coating fluid prescription:
| | 3.2g add to 40 milliliters |
Preparation technology: diclofenac sodium (potassium), glucosamine sulfate, microcrystalline Cellulose, calcium hydrogen phosphate and polyvinylpyrrolidone are crossed 80 mesh sieves, and stearic acid, brazil wax are crossed 60 mesh sieves.Take by weighing above-mentioned adjuvant by recipe quantity, mix homogeneously adds the principal agent of recipe quantity with the equivalent method of progressively increasing, mixing, and guiding humid medium system soft material, 20 mesh sieves are granulated, 50 ℃ of dryings, 20 mesh sieve granulate, the magnesium stearate of adding recipe quantity in dried granule, mixing, tabletting, coating.
Embodiment 52: the preparation of controlled release tablet
A slow-released part prescription is formed:
| C14H10Cl2NNaO2 (potassium) Hydroxypropyl methylcellulose (100000CPS) microcrystalline cellulose ethyl cellulose (10CPS) material) dolomol B immediate release section C14H10Cl2NNaO2 (potassium) Glucosamine Sulphate lactose | 70g (main ingredient) 160g (slow-release material) 15g (adjusting pellet hardness) 7.5g (adhesive and insoluble slowly-releasing material 3g (lubricant) 5g (main ingredient) 250g (main ingredient) 40g (filler) |
| Microcrystalline Cellulose carboxymethyl starch sodium 0.5% hypromellose (5CPS) magnesium stearate | An amount of (binding agent) 0.9g (lubricant) of (29.5g filler) 15g (disintegrating agent) |
| Make | 1000 |
Technology: (1) crosses 80 mesh sieves with diclofenac sodium (potassium) respectively, and glucosamine sulfate is crossed 100 mesh sieves, and it is standby that lactose is crossed 80 mesh sieves.(2) ethyl cellulose of recipe quantity is standby with an amount of wiring solution-forming of dehydrated alcohol; Molten 0.5% aqueous solution that is made into of hypromellose (5CPS) is standby.(3) diclofenac sodium (potassium) is mixed with hypromellose and microcrystalline Cellulose, the adding ethyl cellulose solution stirs and makes soft material, crosses 16 mesh sieves and makes wet grain, at 60 ℃ of dry dry granular P1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular P2, measure the content of diclofenac sodium (potassium) among the dry granular P2, it is heavy to calculate sheet.(4) diclofenac sodium (potassium) (immediate release section), glucosamine sulfate and lactose are mixed by the equivalent mixing method of progressively increasing, adding microcrystalline Cellulose and carboxymethylstach sodium again mixes, the hypromellose solution of adding 0.5% is an amount of, soft material is made in stirring, the soft material that makes is crossed 16 mesh sieves granulate, at 60 ℃ of dry dry granular C1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular C2, measure the content of diclofenac sodium (potassium) and glucosamine sulfate among the dry granular C2, calculate the sheet weight.(5) dry granular P2 and dry granular C2 are put tabletting on the bi-layer tablet press, obtain semi-finished product.The above-mentioned tablet that makes is carried out quality inspection, and qualified back packing gets product.
The preparation of embodiment 53. syrups
| Supplementary material diclofenac sodium (potassium) | Consumption 25g |
| Glucosamine Sulphate Sodium Benzoate citric acid 95% ethanol grapefruit essence sucrose purified water | 300g 2.5g 0.3g 5ml 1ml 650g adds to 1000ml |
| Full dose | 1000ml. |
Preparation technology: get the recipe quantity supplementary material, add total amount 3/5 purified water, heating makes is dissolved into syrup, when being cooled to 60 ℃, above-mentioned solution is added, with adding, when being cooled to below 40 ℃, add benzoic acid solution, citric acid soln and Citrua paradiai essence with stirring, add purified water to full dose, stir, filter, promptly.Take 10ml at every turn.
Embodiment 54: the oral administration solution preparation
| C14H10Cl2NNaO2 (potassium) aminoglucose hydrochloride propane diols glycerine sorbierite asccharin sodium propionic acid acetic acid-sodium-acetate buffer distilled water | 25g 300g 1500ml 2500g 2500g 1.0g 10ml 1600ml is an amount of |
| Full dose | 10000ml (1000). |
Preparation technology: get an amount of distilled water, add sorbitol earlier, heating makes dissolving, and is cold slightly, adds other adjuvant and crude drug, stirs and makes dissolving, and adding distil water is to full dose.Filter with the G4 sintered glass funnel.The filling machine fill is jumped a queue and is rolled lid, sterilizes 30 minutes for 115.5 ℃, examines qualified back packing entirely, promptly.
Embodiment 55: the drop pill preparation
| Diclofenac sodium (potassium) glucosamine sulfate sodium stearate insect wax water | 25g 300g 100g 25g 40g |
Each supplementary material beyond dewatering is added in flask, shakes up, shake up again after adding water, will fill in flask with the rubber closure of reflux condensing tube after, jolting constantly also is heated to about 100 ℃ and makes whole fusions, a glue ball.Be coolant with 2% aqueous sulfuric acid when dripping system.Ooze by the dropper mouth when making medicinal liquid remain on 65 ℃.Because this ball proportion is less than 2% aqueous sulfuric acid, for this reason, during drop pill, melt liquid is splashed in the coolant by the bottom of coolant, and every dropper per minute oozes 200 drop pill approximately.Ball is oozed by the drip place and floats, the cooling of limit rising edge, and drop pill can be pulled out with strainer, is dipped in the acid solution of removing attachment removal in the cold water, inserts in the dish of absorbent paper again, makes rolling, after the water mark on pill surface is removed in suction, promptly.
Embodiment 56: the drop pill preparation
| Diclofenac sodium (potassium) glucosamine sulfate | 25g 300g |
| Polyethylene glycol 6000 | 90g |
Taking polyethylene glycol 6000 is heated to 135 ℃ in oil bath.Add diclofenac sodium (potassium), glucosamine sulfate, constantly be stirred to moltenly entirely, (135 ℃) filter while hot, put in the liquid containing bottle, drip system when making it remain on 135 ℃.The drip internal diameter 9.0mm of rustless steel dropper, external diameter 9.8mm.Drip in the outside with the speed of 80 of per minutes and to form drop pill in the refrigerative liquid paraffin condensed fluid that contains 43% kerosene with frozen water.Ball is taken out the back wash several with flush away kerosene flavor, inhale with writing paper made from bamboo and remove adherent liquid paraffin with liquid paraffin.
Embodiment 57: soft capsule preparation
| Diclofenac sodium (potassium) N-acetylglucosamine PEG400 | 25g 300g (by glucosamine) 400g |
| Make | 1000 |
Two kinds of principal agents with recipe quantity mix with the PEG400 of 1/6 amount earlier, pulverize with colloid mill, add the PEG400 miscible (also available ball mill grinding 3 hours) of surplus then.It is standby that other joins gelatin solution (100 parts in gelatin, 55 parts of glycerol, 120 parts in water).Under the condition of 28 ± 2 ℃ of room temperatures, relative humidity 40%, medicinal liquid and gelatin press capsule machine-processed with rotation automatically, 28 ± 2 ℃, during relative humidity 40% with dry 20 hours of capsule, get product.
Embodiment 58. injectable powder preparation methoies
Prescription: (in 1000)
| Diclofenac sodium (potassium) glucosamine sulfate glycine | 12.5g 100g 400g |
| Anhydrous sodium sulfite disodium edetate water for injection | 40g 4g adds to 2000ml |
| Make | 1000 |
Each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5 ~ 7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, determine canned amount according to content, be sub-packed in the antibiotic glass bottle that half tamponade is put into freeze drying box and carried out lyophilizing, the lyophilizing program is cooled to 0 ℃, freezing 5h for shelf in freeze drying box; Shelf is cooled to-45 ℃ gradually, and freezing 6h starts vacuum pump, closes fridge; Shelf is warming up to-20 ℃ gradually, and evacuation 21h is warming up to 10 ℃ gradually continuously, continuous evacuation 5h, gland outlet.Full inspection, packing, warehouse-in.
Embodiment 59: the aqueous injection preparation method
Prescription: (in 1000)
| Diclofenac sodium (potassium) glucosamine sulfate glycine anhydrous sodium sulfite disodium edetate water for injection | 12.5g 75g 1.2kg 90g 10g adds to 5000ml |
| Make | 1000 |
Preparation technology: each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5～7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, fill, every 5ml.
Embodiment 60: the infusion solution preparation method
| C14H10Cl2NNaO2 (potassium) aminoglucose hydrochloride glycine anhydrous sodium sulfite mosatil glucose injection water | 12.5g 75g 1.2kg 90g 10g 2500g adds to 50000ml |
| Make | 1000 bottles |
Each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5～7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, fill in 50 milliliters of infusion bottles, 115 ℃ of pressure sterilizings 30 minutes.Labeling is packed after the assay was approved.
Embodiment 61: preparation tablets
| Ketoprofen aminoglucose hydrochloride lactose starch sodium | 30g 75g 10g 5.0g 2.7g 0.9g is an amount of |
| Make | 1000 |
Preparation technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting.
Embodiment 62: the capsule preparation
| Ketoprofen glucosamine sulfate pregelatinized Starch microcrystalline Cellulose | 25g 500g 12g 25g |
| 2％HPMC(50cp) | In right amount |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 63: the dispersible tablet preparation
| Supplementary material Ketoprofen 2-Acetamido-2-deoxy-D-glucose sweet | Consumption 50g 75g (by Glucosamine) 25.0g 150ml 10.0g 2.0g 2.0g 2.6g 10.0g |
| Make | 1000 |
Technology: take by weighing polyvinylpyrrolidone by recipe quantity, make 10% solution (1) with 80% ethanol; Take by weighing cross-linking sodium carboxymethyl cellulose, aspartame, micropowder silica gel and the magnesium stearate mix homogeneously (2) of crossing 100 mesh sieves respectively by prescription; Take by weighing ketoprofen, N-acetylglucosamine, mannitol and crospolyvinylpyrrolidone, the mixing of crossing 100 mesh sieves by recipe quantity, cross 80 mesh sieves twice, add (1), 18 mesh sieves are granulated, 60 ± 5 ℃ of oven dry, 20 mesh sieve granulate; Add (2) fully mixing; Tabletting; After the assay was approved, packing.
Embodiment 64: the Film coated tablets preparation
| Ketoprofen 2-Acetamido-2-deoxy-D-glucose dimethoxym ethane lactose starch sodium | 30g 300g (by glucosamine) 10g 3.0g 3g 0.9g 10ml |
| Make | 1000 |
Technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting, (7) substrate Opadry coating solution bag film-coat.
Embodiment 65: the enteric coated capsule preparation
| The pregelatinized Starch of ketoprofen glucosamine hydrochloride | 30g 150g 12g |
| Microcrystalline Cellulose 2%HPMC (50cp) | 25g 1％ |
| Make | 1000 |
Preparation technology: each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; In the dress enteric capsule shell.
Embodiment 66: the capsule preparation
| Sai Laixibu chondroitin sulfate pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 100g 500g 12g 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 67: preparation tablets
| Nabumetone Glucosamine Sulfate Potassium salt hyprolose microcrystalline Cellulose | 250g 100g (by glucosamine) 14g 11.2g |
| 30 POVIDONE K 30 BP/USP 30 sodium lauryl sulphate magnesium stearate ethanol | 3.9g 1.4g 0.84g is an amount of |
| Make | 1000 |
Preparation technology: 1. take by weighing nabumetone, Glucosamine Sulfate Potassium salt, hyprolose, microcrystalline Cellulose, mix homogeneously.2. pulverize, once more mix homogeneously.3. make suitable soft material with 10% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution.4. 14 order nylon wires are granulated.5. rapid draing below 60 ℃.6. add sodium lauryl sulphate, magnesium stearate, mix homogeneously.7. 12 order nylon wire granulate.8. use the flat stamping of Ф 8mm, the heavy 0.28g of control strip.9. pack after the assay was approved.
Embodiment 68: the granule preparation
| | 250g 250g (by glucosamine) 30g is an amount of |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. nabumetone, chitin are pulverized, and cross 80 mesh sieves.3. take by weighing nabumetone and cane sugar powder, mix homogeneously.4. make suitable soft material with 10% starch slurry.5. 12 order nylon wires are granulated.6. granule is in rapid draing below 50-60 ℃, and control moisture is below 1%.7. use 12 order nylon wire granulate.8. add spice, mix homogeneously.9. after the assay was approved, pack, packing.
Embodiment 69: the preparation of dry suspension
| Ketoprofen N-acetylglucosamine hyprolose xanthan gum spice cane sugar powder | 12.5g 150g (by glucosamine) 36g 30g 30g 2404g |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. accurately take by weighing each supplementary material.3. above-mentioned mixing of materials is pulverized, and crosses 80 mesh sieves.4. material mixes once more, sample examination.5. pack, pack.
Embodiment 70: the preparation of slow releasing capsule
Ball core prescription:
| Ketoprofen aminoglucose hydrochloride blank pill core 90% ethanol dressing prescription: Eudragit RS EC 95% ethanol | An amount of 42g 42g of 90g 200g (by Glucosamine) 262.5g is an amount of |
| Make | 1000 |
Preparation technology: ketoprofen, PVPK30 are dissolved in 90% ethanol, wind pressure 0.7bar is gone in start, pours the ball core of recipe quantity in the pot into, spray principal agent, PVPK30 mixed solution, CAPL is 1.0bar, and CYL is 2.3bar, and rotating speed is 145rpm, the revolution speed 10% of wriggling, SV48 ℃ of inlet air temperature, PV48 ℃, product temperature SV19 ℃, PV22 ℃, 60 ℃ of oven dry.
Eudragit RS and EC are dissolved in 95% ethanol, are made into coating solution, start, go into wind pressure 0.7bar, pour above-mentioned ball core in the pot, the spray coating solution, CAPL is 0.9bar, CYL is 2.3bar, rotating speed is 150rpm, the revolution speed 6% of wriggling, SV29 ℃ of inlet air temperature, PV29 ℃, product temperature SV19 ℃, PV22 ℃, 40 ℃ of oven dry.Add glucosamine hydrochloride, magnesium stearate, mixing detects intermediate, determines loading amount, the dress capsule.
Embodiment 71: the preparation of slow releasing tablet
The label prescription:
| Ketoprofen Glucosamine Sulphate polyvinylpyrrolidone stearic acid brazil wax microcrystalline cellulose | 60g 200g (by Glucosamine) 20g 20g 70g 40g 20g an amount of 0.5% | |
| Make | 1000 | |
Coating fluid prescription:
| The Opadry coating powder | 3.2g |
| 50% alcoholic solution | Add to 40 milliliters |
Preparation technology: ketoprofen, glucosamine sulfate, microcrystalline Cellulose, calcium hydrogen phosphate and polyvinylpyrrolidone are crossed 80 mesh sieves, and stearic acid, brazil wax are crossed 60 mesh sieves.Take by weighing above-mentioned adjuvant by recipe quantity, mix homogeneously adds the principal agent of recipe quantity with the equivalent method of progressively increasing, mixing, and guiding humid medium system soft material, 20 mesh sieves are granulated, 50 ℃ of dryings, 20 mesh sieve granulate, the magnesium stearate of adding recipe quantity in dried granule, mixing, tabletting, coating.
Embodiment 72: the preparation of controlled release tablet
A slow-released part prescription is formed:
| Ketoprofen Hydroxypropyl methylcellulose (100000CPS) microcrystalline cellulose ethyl cellulose (10CPS) material) dolomol B immediate release section Ketoprofen Glucosamine Sulphate lactose microcrystal carboxymethyl cellulose Starch Sodium 0.5% Hydroxypropyl methylcellulose (5CPS) dolomol | 70g (main ingredient) 160g (slow-release material) 15g (adjusting pellet hardness) 7.5g (an amount of (adhesive) 0.9g (lubricant) of adhesive and insoluble slowly-releasing material 3g (lubricant) 5g (main ingredient) 250g (main ingredient) 40g (filler) 29.5g (filler) 15g (disintegrant) |
| Make | 1000 |
Technology: (1) crosses ketoprofen 80 mesh sieves respectively, and glucosamine sulfate is crossed 100 mesh sieves, and it is standby that lactose is crossed 80 mesh sieves.(2) ethyl cellulose of recipe quantity is standby with an amount of wiring solution-forming of dehydrated alcohol; Molten 0.5% aqueous solution that is made into of hypromellose (5CPS) is standby.(3) ketoprofen is mixed with hypromellose and microcrystalline Cellulose, the adding ethyl cellulose solution stirs and makes soft material, crosses 16 mesh sieves and makes wet grain, at 60 ℃ of dry dry granular P1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular P2, measure the content of ketoprofen among the dry granular P2, it is heavy to calculate sheet.(4) ketoprofen (immediate release section), glucosamine sulfate and lactose are mixed by the equivalent mixing method of progressively increasing, adding microcrystalline Cellulose and carboxymethylstach sodium again mixes, the hypromellose solution of adding 0.5% is an amount of, soft material is made in stirring, the soft material that makes is crossed 16 mesh sieves granulate, at 60 ℃ of dry dry granular C1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular C2, measure the content of ketoprofen and glucosamine sulfate among the dry granular C2, it is heavy to calculate sheet.(5) dry granular P2 and dry granular C2 are put tabletting on the bi-layer tablet press, obtain semi-finished product.The above-mentioned tablet that makes is carried out quality inspection, and qualified back packing gets product.
The preparation of embodiment 73. syrups
| Supplementary material Ketoprofen Glucosamine Sulphate Sodium Benzoate citric acid 95% ethanol grapefruit essence | Consumption 25g 300g 2.5g 0.3g 5ml 1ml |
| The sucrose purified water | 650g adds to 1000ml |
| Full dose | 1000ml. |
Preparation technology: get the recipe quantity supplementary material, add total amount 3/5 purified water, heating makes is dissolved into syrup, when being cooled to 60 ℃, above-mentioned solution is added, with adding, when being cooled to below 40 ℃, add benzoic acid solution, citric acid soln and Citrua paradiai essence with stirring, add purified water to full dose, stir, filter, promptly.Take 10ml at every turn.
Embodiment 74: the oral administration solution preparation
| Ketoprofen aminoglucose hydrochloride propane diols glycerine sorbierite asccharin sodium propionic acid acetic acid-sodium-acetate buffer distilled water | 25g 300g 1500ml 2500g 2500g 1.0g 10ml 1600ml is an amount of |
| Full dose | 10000ml (1000). |
Preparation technology: get an amount of distilled water, add sorbitol earlier, heating makes dissolving, and is cold slightly, adds other adjuvant and crude drug, stirs and makes dissolving, and adding distil water is to full dose.Filter with the G4 sintered glass funnel.The filling machine fill is jumped a queue and is rolled lid, sterilizes 30 minutes for 115.5 ℃, examines qualified back packing entirely, promptly.
Embodiment 75: the drop pill preparation
| Ketoprofen glucosamine sulfate sodium stearate insect wax water | 25g 300g 100g 25g 40g |
Each supplementary material beyond dewatering is added in flask, shakes up, shake up again after adding water, will fill in flask with the rubber closure of reflux condensing tube after, jolting constantly also is heated to about 100 ℃ and makes whole fusions, a glue ball.Be coolant with 2% aqueous sulfuric acid when dripping system.Ooze by the dropper mouth when making medicinal liquid remain on 65 ℃.Because this ball proportion is less than 2% aqueous sulfuric acid, for this reason, during drop pill, melt liquid is splashed in the coolant by the bottom of coolant, and every dropper per minute oozes 200 drop pill approximately.Ball is oozed by the drip place and floats, the cooling of limit rising edge, and drop pill can be pulled out with strainer, is dipped in the acid solution of removing attachment removal in the cold water, inserts in the dish of absorbent paper again, makes rolling, after the water mark on pill surface is removed in suction, promptly.
Embodiment 76: the drop pill preparation
| Flurbiprofen glucosamine sulfate polyethylene glycol 6000 | 50g 300g 90g |
Taking polyethylene glycol 6000 is heated to 135 ℃ in oil bath.Add flurbiprofen, glucosamine sulfate, constantly be stirred to moltenly entirely, (135 ℃) filter while hot, put in the liquid containing bottle, drip system when making it remain on 135 ℃.The drip internal diameter 9.0mm of rustless steel dropper, external diameter 9.8mm.Drip in the outside with the speed of 80 of per minutes and to form drop pill in the refrigerative liquid paraffin condensed fluid that contains 43% kerosene with frozen water.Ball is taken out the back wash several with flush away kerosene flavor, inhale with writing paper made from bamboo and remove adherent liquid paraffin with liquid paraffin.
Embodiment 77: soft capsule preparation
| Ketoprofen N-acetylglucosamine PEG400 | 25g 300g (by glucosamine) 400g |
| Make | 1000 |
Two kinds of principal agents with recipe quantity mix with the PEG400 of 1/6 amount earlier, pulverize with colloid mill, add the PEG400 miscible (also available ball mill grinding 3 hours) of surplus then.It is standby that other joins gelatin solution (100 parts in gelatin, 55 parts of glycerol, 120 parts in water).Under the condition of 28 ± 2 ℃ of room temperatures, relative humidity 40%, medicinal liquid and gelatin press capsule machine-processed with rotation automatically, 28 ± 2 ℃, during relative humidity 40% with dry 20 hours of capsule, get product.
Embodiment 78. injectable powder preparation methoies
Prescription: (in 1000)
| Flurbiprofen glucosamine sulfate glycine anhydrous sodium sulfite disodium edetate water for injection | 50g 100g 400g 40g 4g adds to 2000ml |
| Make | 1000 |
Each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5 ~ 7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, determine canned amount according to content, be sub-packed in the antibiotic glass bottle that half tamponade is put into freeze drying box and carried out lyophilizing, the lyophilizing program is cooled to 0 ℃, freezing 5h for shelf in freeze drying box; Shelf is cooled to-45 ℃ gradually, and freezing 6h starts vacuum pump, closes fridge; Shelf is warming up to-20 ℃ gradually, and evacuation 21h is warming up to 10 ℃ gradually continuously, continuous evacuation 5h, gland outlet.Full inspection, packing, warehouse-in.
Embodiment 79: the aqueous injection preparation method
Prescription: (in 1000)
| Pyrrole sieve Xikang glucosamine sulfate glycine anhydrous sodium sulfite disodium edetate water for injection | 10g 75g 1.2kg 90g 10g adds to 5000ml |
| Make | 1000 |
Preparation technology: each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5～7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, fill, every 5ml.
Embodiment 80: the infusion solution preparation method
| Naproxen aminoglucose hydrochloride glycine anhydrous sodium sulfite mosatil glucose injection water | 100g 75g 1.2kg 90g 10g 2500g adds to 50000ml |
| Make | 1000 bottles |
Each component that takes by weighing recipe quantity adds an amount of water for injection in the dosing cylinder, stirs to make whole dissolvings, and be 5.5～7.5 with the hydrochloric acid of 0.1M or the sodium hydroxide solution adjusting pH value of 0.1M, be settled to the full dose of recipe quantity then with water for injection.The active carbon room temperature that adds recipe quantity 0.1% (g/ml) in the medicinal liquid stirs about 30min the plate-and-frame filtration decarburization.Cross 1.0 μ m, 0.45 μ m, 0.2 μ m degerming filter membrane successively.Check clarity, the pH value of filtrate, measure the content of two principal agents.After the filtrate passed examination, fill in 50 milliliters of infusion bottles, 115 ℃ of pressure sterilizings 30 minutes.Labeling is packed after the assay was approved.
Embodiment 81: preparation tablets
| Clofenamic acid glucosamine hydrochloride lactose | 125g 75g 10g |
| Starch carboxymethyl starch |
5.0g 2.7g 0.9g is an amount of |
| Make | 1000 |
Preparation technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting.
Embodiment 82: the capsule preparation
| Fenoprofen calcium glucosamine sulfate pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 200g 500g 12g 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 83: the dispersible tablet preparation
| Supplementary material sulindac 2-Acetamido-2-deoxy-D-glucose sweet | Consumption 100g 75g (by Glucosamine) 25.0g 150ml 10.0g 2.0g 2.0g 2.6g 10.0g |
| Make | 1000 |
Technology: take by weighing polyvinylpyrrolidone by recipe quantity, make 10% solution (1) with 80% ethanol; Take by weighing cross-linking sodium carboxymethyl cellulose, aspartame, micropowder silica gel and the magnesium stearate mix homogeneously (2) of crossing 100 mesh sieves respectively by prescription; Take by weighing ketoprofen, N-acetylglucosamine, mannitol and crospolyvinylpyrrolidone, the mixing of crossing 100 mesh sieves by recipe quantity, cross 80 mesh sieves twice, add (1), 18 mesh sieves are granulated, 60 ± 5 ℃ of oven dry, 20 mesh sieve granulate; Add (2) fully mixing; Tabletting; After the assay was approved, packing.
Embodiment 84: the Film coated tablets preparation
| Ketorolac trometamol N-acetylglucosamine dimethoxym ethane | 10g 300g (by glucosamine) |
| Lactose starch carboxymethyl starch |
10g 3.0g 3g 0.9g 10ml |
| Make | 1000 |
Technology: (1) principal agent and adjuvant pulverize separately, principal agent is crossed 120 mesh sieves, and adjuvant is crossed 100 mesh sieves, and is standby.(2) principal agent that accurately takes by weighing recipe quantity mixes with the equivalent dilution method of progressively increasing with the part lactose, crosses 100 mesh sieves three times, gets female powder.(3) remainder lactose, starch and Nei Jia part disintegrating agent mix homogeneously are crossed 80 mesh sieves three times, get the adjuvant mixture.(4) female powder and adjuvant mixture mixing are crossed 80 mesh sieves three times, and it is an amount of to add 10% starch slurry, makes soft material, cross 18 mesh sieves and granulate, 50～60 ℃ of dryings three hours.(5) 16 mesh sieve granulate add Extra Section disintegrating agent, magnesium stearate, mixing.(6) tabletting, (7) substrate Opadry coating solution bag film-coat.
Embodiment 85: the enteric coated capsule preparation
| Nabumetone glucosamine hydrochloride pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 30g 150g 12g 25g 1％ |
| Make | 1000 |
Preparation technology: each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; In the dress enteric capsule shell.
Embodiment 86: the capsule preparation
| Xikang, U.S. Lip river chondroitin sulfate pregelatinized Starch microcrystalline Cellulose 2%HPMC (50cp) | 7.5g 500g 12g 25g is an amount of |
| Make | 1000 |
Preparation technology: with each supplementary material pulverize separately, cross 100 mesh sieves, take by weighing by recipe quantity, fully mixing is crossed 80 mesh sieves and is mixed 3 times; Add 2% hypromellose and make soft material in right amount; Crossing 30 mesh sieves granulates; 55 ℃ of oven dry; 20 mesh sieve granulate; Survey intermediate content; The dress capsule.
Embodiment 87: preparation tablets
| Olsapozine Glucosamine sulfate potassium chloride L-HPC microcrystalline cellulose PVP K30 lauryl sodium sulfate magnesium stearate ethanol | 125g 100g (by Glucosamine) 14g 11.2g 3.9g 1.4g 0.84g is an amount of |
| Make | 1000 |
Preparation technology: 1. take by weighing oxaprozin, Glucosamine Sulfate Potassium salt, hyprolose, microcrystalline Cellulose, mix homogeneously.2. pulverize, once more mix homogeneously.3. make suitable soft material with 10% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution.4. 14 order nylon wires are granulated.5. rapid draing below 60 ℃.6. add sodium lauryl sulphate, magnesium stearate, mix homogeneously.7. 12 order nylon wire granulate.8. use the flat stamping of Ф 8mm, the heavy 0.28g of control strip.9. pack after the assay was approved.
Embodiment 88: the granule preparation
| Acemetacin N-acetylglucosamine | 30g 250g (by glucosamine) 30g is an amount of |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. acemetacin, chitin are pulverized, and cross 80 mesh sieves.3. take by weighing acemetacin and cane sugar powder, mix homogeneously.4. make suitable soft material with 10% starch slurry.5. 12 order nylon wires are granulated.6. granule is in rapid draing below 50-60 ℃, and control moisture is below 1%.7. use 12 order nylon wire granulate.8. add spice, mix homogeneously.9. after the assay was approved, pack, packing.
Embodiment 89: the preparation of dry suspension
| Sai Laixibu N-acetylglucosamine hyprolose xanthan gum | 100g 150g (by glucosamine) 36g 30g |
| The spice cane sugar powder | 30g 2404g |
| Make | 1000 bags |
Technology: 1. sucrose is dried to moisture about 1%, pulverizes standby.2. accurately take by weighing each supplementary material.3. above-mentioned mixing of materials is pulverized, and crosses 80 mesh sieves.4. material mixes once more, sample examination.5. pack, pack.
Embodiment 90: the preparation of slow releasing capsule
Ball core prescription:
| Naproxen 2-Acetamido-2-deoxy-D-glucose blank pill core 90% ethanol dressing prescription: Eudragit RS EC 95% ethanol | An amount of 42g 42g of 250g 200g (by Glucosamine) 262.5g is an amount of |
| Make | 1000 |
Preparation technology: naproxen, PVPK30 are dissolved in 90% ethanol, wind pressure 0.7bar is gone in start, pours the ball core of recipe quantity in the pot into, spray principal agent, PVPK30 mixed solution, CAPL is 1.0bar, and CYL is 2.3bar, and rotating speed is 145rpm, the revolution speed 10% of wriggling, SV48 ℃ of inlet air temperature, PV48 ℃, product temperature SV19 ℃, PV22 ℃, 60 ℃ of oven dry.
Eudragit RS and EC are dissolved in 95% ethanol, are made into coating solution, start, go into wind pressure 0.7bar, pour above-mentioned ball core in the pot, the spray coating solution, CAPL is 0.9bar, CYL is 2.3bar, rotating speed is 150rpm, the revolution speed 6% of wriggling, SV29 ℃ of inlet air temperature, PV29 ℃, product temperature SV19 ℃, PV22 ℃, 40 ℃ of oven dry.Add N-acetylglucosamine, magnesium stearate, mixing detects intermediate, determines loading amount, the dress capsule.
Embodiment 91: the preparation of slow releasing tablet
The label prescription:
| Brufen Glucosamine Sulphate polyvinylpyrrolidone stearic acid brazil wax microcrystalline cellulose | 250g 200g (by Glucosamine) 20g 20g 70g 40g 20g an amount of 0.5% | |
| Make | 1000 | |
Coating fluid prescription:
| | 3.2g add to 40 milliliters |
Preparation technology: ibuprofen, glucosamine sulfate, microcrystalline Cellulose, calcium hydrogen phosphate and polyvinylpyrrolidone are crossed 80 mesh sieves, and stearic acid, brazil wax are crossed 60 mesh sieves.Take by weighing above-mentioned adjuvant by recipe quantity, mix homogeneously adds the principal agent of recipe quantity with the equivalent method of progressively increasing, mixing, and guiding humid medium system soft material, 20 mesh sieves are granulated, 50 ℃ of dryings, 20 mesh sieve granulate, the magnesium stearate of adding recipe quantity in dried granule, mixing, tabletting, coating.
Embodiment 92: the preparation of controlled release tablet
A slow-released part prescription is formed:
| Nabumetone Hydroxypropyl methylcellulose (100000CPS) microcrystalline cellulose ethyl cellulose (10CPS) material) dolomol B immediate release section nabumetone Glucosamine Sulphate lactose microcrystal carboxymethyl cellulose Starch Sodium 0.5% Hydroxypropyl methylcellulose (5CPS) dolomol | 125g (main ingredient) 160g (slow-release material) 15g (adjusting pellet hardness) 7.5g (an amount of (adhesive) 0.9g (lubricant) of adhesive and insoluble slowly-releasing material 3g (lubricant) 30g (main ingredient) 250g (main ingredient) 40g (filler) 29.5g (filler) 15g (disintegrant) |
| Make | 1000 |
Technology: (1) crosses nabumetone 80 mesh sieves respectively, and glucosamine sulfate is crossed 100 mesh sieves, and it is standby that lactose is crossed 80 mesh sieves.(2) ethyl cellulose of recipe quantity is standby with an amount of wiring solution-forming of dehydrated alcohol; Molten 0.5% aqueous solution that is made into of hypromellose (5CPS) is standby.(3) nabumetone is mixed with hypromellose and microcrystalline Cellulose, the adding ethyl cellulose solution stirs and makes soft material, crosses 16 mesh sieves and makes wet grain, at 60 ℃ of dry dry granular P1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular P2, measure the content of nabumetone among the dry granular P2, it is heavy to calculate sheet.(4) nabumetone (immediate release section), glucosamine sulfate and lactose are mixed by the equivalent mixing method of progressively increasing, adding microcrystalline Cellulose and carboxymethylstach sodium again mixes, the hypromellose solution of adding 0.5% is an amount of, soft material is made in stirring, the soft material that makes is crossed 16 mesh sieves granulate, at 60 ℃ of dry dry granular C1 that get; After dry granular crossed 16 mesh sieve granulate, mix with magnesium stearate, dry granular C2, measure the content of nabumetone and glucosamine sulfate among the dry granular C2, it is heavy to calculate sheet.(5) dry granular P2 and dry granular C2 are put tabletting on the bi-layer tablet press, obtain semi-finished product.The above-mentioned tablet that makes is carried out quality inspection, and qualified back packing gets product.
Claims (9)
1, a kind of composition of medicine that contains nonsteroidal anti-inflammatory analgetic (NSAIDs) is characterized in that composition of medicine is made up of nonsteroidal anti-inflammatory analgetic part and two kinds of ingredients of glucosamine part, and all the other are the adjuvant in the pharmaceutics.
2, composition of medicine according to claim 1 is characterized in that the medicine with the nonsteroidal anti-inflammatory analgetic compatibility is glucosamine or its hydrochlorate, sulfate monomer or sulphuric acid potassium salt, sodium sulfate salt etc.; Also can be glucosamine derivants such as N-acetylglucosamine dimethoxym ethane, N-acetylglucosamine; Also can be materials such as the chitin that can be decomposed into glucosamine, chrondroitin.
3,, it is characterized in that said nonsteroidal anti-inflammatory analgetic (NSAIDs) is ibuprofen, naproxen (or naproxen sodium), oxaprozin, fenoprofen calcium, flurbiprofen, loxoprofen (loxoprofen sodium), pranoprofen, diclofenac sodium (potassium), lornoxicam, etodolac, clofenamic acid, piroxicam, indomethacin, acemetacin, nabumetone, sulindac, diclofenac sodium (or diclofenac potassium), ketorolac trometamol, meloxicam or celecoxib according to claim 1 and 2 described composition of medicine.
4, according to the described composition of medicine of claim 1～3, the dosage form that it is characterized in that this composition of medicine is oral formulations, injection and ophthalmic preparation.
5, according to the described composition of medicine of claim 1～3, it is characterized in that nonsteroidal anti-inflammatory analgetic partly is all the enteric part separately or with glucosamine in this composition of medicine, after the oral administration administration, discharge at intestinal.
6, according to the described composition of medicine of claim 1～3, it is characterized in that nonsteroidal anti-inflammatory analgetic in this composition of medicine partly is all slow controlled release part in the pharmaceutics separately or with glucosamine, after the oral administration administration, slowly discharge, slow constant release or slowly near constant release.
7, according to the described composition of medicine of claim 1～4, each sheet that it is characterized in that this combined pharmaceutical formulation, grain, or other each unit formulation in, the amount of glucosamine part (by the glucosamine molecule) is 50mg～1000mg, and the amount of nonsteroidal anti-inflammatory analgetic part is respectively: ibuprofen 25mg～500mg, naproxen 25mg～750mg, oxaprozin 50mg～500mg, fenoprofen calcium 100mg～1000mg, flurbiprofen 25mg～250mg, loxoprofen (loxoprofen sodium) 25mg～200mg, pranoprofen 25mg～250mg, diclofenac sodium (potassium) 10mg～300mg, lornoxicam 1mg～25mg, etodolac 50mg～500mg, clofenamic acid 50mg～500mg, piroxicam 3mg～100mg, indomethacin 5.5mg～150mg, acemetacin 7.5mg～150mg, nabumetone 50mg～1500mg, sulindac 50mg～500mg, diclofenac sodium (or diclofenac potassium) 10mg～150mg, ketorolac trometamol 2mg～50mg, meloxicam 2mg～25mg or celecoxib 50mg～800mg.
8, according to the described composition of medicine of claim 1～4, each sheet that it is characterized in that this combined pharmaceutical formulation, grain, or other each unit formulation in, the amount of glucosamine part (by the glucosamine molecule) is 50mg～750mg, and the amount of nonsteroidal anti-inflammatory analgetic part is respectively: and ibuprofen 50mg～250mg (250mg in the sustained-release preparation～400mg), naproxen 50mg～500mg (250mg in the sustained-release preparation～500mg), oxaprozin 150mg～300mg (150mg in the sustained-release preparation～400mg), fenoprofen calcium 150mg～600mg (200mg in the sustained-release preparation～800mg), flurbiprofen 50mg～200mg (50mg in the sustained-release preparation～300mg), loxoprofen 25mg～150mg (25mg in the sustained-release preparation～300mg), pranoprofen 25mg～125mg (25mg in the sustained-release preparation～250mg), diclofenac sodium (potassium) 10mg～100mg (50mg in the sustained-release preparation～300mg), lornoxicam 2mg～10mg (2mg in the sustained-release preparation～20mg), etodolac 100mg～500mg (200mg in the sustained-release preparation～500mg), clofenamic acid 100mg～300mg (100mg in the sustained-release preparation～400mg), piroxicam 5mg～60mg (10mg in the sustained-release preparation～100mg), indomethacin 5.5mg～90mg (25mg in the sustained-release preparation～120mg), acemetacin 7.5mg～100mg (25mg in the sustained-release preparation～120mg), nabumetone 100mg～750mg (200mg in the sustained-release preparation～1000mg), sulindac 50mg～300mg (150mg in the sustained-release preparation～500mg), diclofenac sodium (potassium) 10mg～100mg (25mg in the sustained-release preparation～100mg), ketorolac trometamol 5mg～25mg (5mg in the sustained-release preparation～90mg), meloxicam 5mg～20mg (5mg in the sustained-release preparation～25mg) or celecoxib 50mg～500mg (100mg in the sustained-release preparation～800mg).
9, according to the described composition of medicine of claim 1 to 4, it is characterized in that clinical human ankylosing spondylitis, the cervical spondylosis of being used for of this composition of medicine, also can be used for the treatment of scapulohumeral periarthritis, rheumatic or rheumatoid arthritis etc., and the non-infectious inflammation that causes of ophthalmologic operation or non-operation factor.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101357124B (en) * | 2007-07-30 | 2010-12-22 | 中国医药研究开发中心有限公司 | Medicine for treating osteoarthritis |
| WO2011083291A1 (en) * | 2010-01-07 | 2011-07-14 | Julian Manuel Galvez | Combinations comprising an ant i -inflammatory agent and/or an antibacterial agent and a glycosylamine and their use in medicine |
| CN102266563A (en) * | 2011-07-13 | 2011-12-07 | 赵磊 | Compound analgesic composition and preparation method thereof |
| CN102670531A (en) * | 2012-04-19 | 2012-09-19 | 迪沙药业集团有限公司 | Loxoprofen sodium composition |
| CN102895207A (en) * | 2012-11-16 | 2013-01-30 | 天津中新药业集团股份有限公司新新制药厂 | Diclofenac sodium sustained-release tablet and preparation method thereof |
| CN103432067A (en) * | 2013-08-31 | 2013-12-11 | 西南大学 | Ketoprofen solution and preparation method thereof |
| CN106913518A (en) * | 2017-03-10 | 2017-07-04 | 广州奥博医药科技有限公司 | A kind of precursor type non-steroidal anti-inflammatory gel for eye use and preparation method thereof |
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| CN115317464A (en) * | 2022-09-01 | 2022-11-11 | 苏州弘森药业股份有限公司 | Diclofenac potassium microcapsule and preparation method thereof |
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|---|---|---|---|---|
| CN101357124B (en) * | 2007-07-30 | 2010-12-22 | 中国医药研究开发中心有限公司 | Medicine for treating osteoarthritis |
| WO2011083291A1 (en) * | 2010-01-07 | 2011-07-14 | Julian Manuel Galvez | Combinations comprising an ant i -inflammatory agent and/or an antibacterial agent and a glycosylamine and their use in medicine |
| CN102266563A (en) * | 2011-07-13 | 2011-12-07 | 赵磊 | Compound analgesic composition and preparation method thereof |
| CN102670531B (en) * | 2012-04-19 | 2015-11-11 | 迪沙药业集团有限公司 | A kind of Loxoprofen sodium composition |
| CN102670531A (en) * | 2012-04-19 | 2012-09-19 | 迪沙药业集团有限公司 | Loxoprofen sodium composition |
| CN102895207A (en) * | 2012-11-16 | 2013-01-30 | 天津中新药业集团股份有限公司新新制药厂 | Diclofenac sodium sustained-release tablet and preparation method thereof |
| CN102895207B (en) * | 2012-11-16 | 2013-10-09 | 天津中新药业集团股份有限公司新新制药厂 | Diclofenac sodium sustained-release tablet and preparation method thereof |
| CN103432067A (en) * | 2013-08-31 | 2013-12-11 | 西南大学 | Ketoprofen solution and preparation method thereof |
| CN106913518A (en) * | 2017-03-10 | 2017-07-04 | 广州奥博医药科技有限公司 | A kind of precursor type non-steroidal anti-inflammatory gel for eye use and preparation method thereof |
| CN112870154A (en) * | 2021-02-03 | 2021-06-01 | 四川农业大学 | Veterinary compound celecoxib nanoliposome gel and preparation method thereof |
| CN112870154B (en) * | 2021-02-03 | 2022-10-18 | 四川农业大学 | Veterinary compound celecoxib nanoliposome gel and preparation method thereof |
| CN115317464A (en) * | 2022-09-01 | 2022-11-11 | 苏州弘森药业股份有限公司 | Diclofenac potassium microcapsule and preparation method thereof |
| CN115317464B (en) * | 2022-09-01 | 2023-08-08 | 苏州弘森药业股份有限公司 | Potassium diclofenac microcapsule and preparation method thereof |
| CN117017932A (en) * | 2023-08-24 | 2023-11-10 | 浙江和沐康医药科技有限公司 | Sulindac tablet composition and preparation method and application thereof |
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