CN100525765C - Lappaconitine hydrobromide dispersible tablet and its preparing method - Google Patents
Lappaconitine hydrobromide dispersible tablet and its preparing method Download PDFInfo
- Publication number
- CN100525765C CN100525765C CNB2006100124512A CN200610012451A CN100525765C CN 100525765 C CN100525765 C CN 100525765C CN B2006100124512 A CNB2006100124512 A CN B2006100124512A CN 200610012451 A CN200610012451 A CN 200610012451A CN 100525765 C CN100525765 C CN 100525765C
- Authority
- CN
- China
- Prior art keywords
- parts
- lappaconitine hydrobromide
- polyvinylpolypyrrolidone
- dispersible tablet
- microcrystalline cellulose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a lappaconitine preparation, in the concrete, it relates to a lappaconitine dispersion tablet and its preparation method. Its composition includes lappaconitine, avicel, cross-linked povidone and micropowder silica gel. Besides, said invention also provides the concrete steps of its preparation method.
Description
Technical field
The present invention relates to a kind of lappaconitine hydrobromide preparation, be specially a kind of Lappaconitine hydrobromide dispersible tablet and preparation method thereof.
Background technology
Lappaconitine hydrobromide (C
32H
44N
2O
8HBrH
2O) be to extract the hydrobromate that the effective ingredient that obtains draws the handkerchief aconitine in the cohosh Aconitum sinomontanum Nakai root, be unimolecule, the non-narcotic analgesics thing of pure natural.Mainly be sodium-ion channel, suppress nerve conduction, suppress the reuptake of presynaptic membrane, the norepinephrine between synapse is increased, thereby suppress the release of centripetal fiber P material norepinephrine by the retardance voltage dependent, and the performance analgesic effect.Its analgesic activity is compared with dolantin, and analgesic effect is suitable, and effect holds time longlyer, and analgesic activity is 7 times of antipyretic analgesic aminophenazone.Lappaconitine hydrobromide has stronger analgesic activity, is used for the treatment of the above pain of moderate.Have wide accommodation, characteristics that analgesic effect is good, can be used as the preferred agents of treatment cancer pain, that uses clinically now mainly contains dosage forms such as lappaconitine hydrobromide injection, injection lappaconitine hydrobromide, lappaconitine hydrobromide sheet (ordinary tablet), lappaconitine hydrobromide card sheet.Lappaconitine hydrobromide is low dose of, insoluble drug, and this product is dissolved in methanol, and soluble,very slightly in ethanol is almost insoluble in chloroform.Because this medicine belongs to analgesic, require its preparation to absorb clinically and want fast with onset, just can reach rapid aim of alleviating pain and effect, and commercially available lappaconitine hydrobromide sheet belongs to conventional tablet, the character of the adjuvant that uses in the preparation and cause its disintegration time long, dissolution is low, and it is slow that patient takes the back onset, can't satisfy clinical needs.This dosage form of dispersible tablet mainly is applicable to insoluble drug and the medicine of bioavailability problem arranged, and is not suitable for that toxic and side effects is big, safety coefficient medicine lower and soluble in water.
Summary of the invention
The present invention provides a kind of Lappaconitine hydrobromide dispersible tablet and preparation method thereof in order to solve the slow and low problem of dissolution of the common lappaconitine hydrobromide sheet disintegrate that exists in the prior art.
The present invention is realized by following technical scheme: a kind of Lappaconitine hydrobromide dispersible tablet, to form by the raw material of following weight ratio, and 5 parts of lappaconitine hydrobromide are (with C
32H
44N
2O
8H
2The O meter), 42～78 parts of microcrystalline Cellulose, 21～39 parts of polyvinylpolypyrrolidone, 7～13 parts of micropowder silica gels.
The preparation method of dispersible tablet can be existing conventional process technology.Generally be with the lappaconitine hydrobromide after pulverizing, microcrystalline Cellulose, mix the back granulation, more remaining polyvinylpolypyrrolidone and micropowder silica gel mix homogeneously, tabletting are got final product with the polyvinylpolypyrrolidone of part.
One of concrete preparation method is: 5 parts lappaconitine hydrobromide are pulverized, crossed 100～120 mesh sieves; The polyvinylpolypyrrolidone of 42～78 parts microcrystalline Cellulose and 21～39 parts is crossed 100～120 mesh sieves respectively, again with the polyvinylpolypyrrolidone mix homogeneously of lappaconitine hydrobromide and microcrystalline Cellulose and 1/3～2/3 prescription weight, cross 60～100 mesh sieves, ratio in the moistening said mixture total amount 10～25ml/100g of want adds ethanol again, abundant mixing, granulate, drying, the micropowder silica gel mix homogeneously, the tabletting that add remaining polyvinylpolypyrrolidone and 8～11 parts again get final product.
Lappaconitine hydrobromide is an active component, and microcrystalline Cellulose is a filler, and polyvinylpolypyrrolidone is disintegrating agent and binding agent, and ethanol is wetting agent, and micropowder silica gel is a fluidizer.
Quality and effect expert evidence,
1, disintegration time contrast is as table 1
The present invention is a dispersible tablet, should consider at first that when the design prescription tablet can rapid disintegrate be a granule in water, and can form uniform suspension, will consider that also the stripping of tablet should meet the requirements simultaneously; The source of adjuvant should be easy to get, and is easy to granulation, tabletting, mobility of particle is good, tablet weight variation is little etc.
Table 1
| Prescription | 1 2 3 4 5 6 |
| Principal agent (mg) | 5 5 5 5 5 5 |
| Microcrystalline Cellulose Homemade(mg) | 50 60 60 60 ---- ---- |
| Microcrystalline Cellulose 301(mg) | ---- ---- ---- ---- 70 60 |
| Low-substituted hydroxypropyl methylcellulose (mg) | 10 ---- ---- ---- ---- ---- |
| Lactose (mg) | 20 ---- ---- ---- ---- ---- |
| Micropowder silica gel (mg) | ---- ---- 10 10 10 10 |
| Carboxymethyl starch sodium (mg) | ---- ---- ---- 40 ---- ---- |
| Polyvinylpolypyrrolidone (mg) | 10 30 40 10 20 30 |
| 70% ethanol | qs qs qs qs qs qs |
| Magnesium stearate (mg) | 10 10 ---- ---- ---- ---- |
| Complete disintegration time (min) | 6.8 4.5 3.3 2.8 1.9 1.5 |
The kind of disintegrating agent and consumption are most important to disintegrate, the result of extraction of dispersible tablet.According to above-mentioned 6 formulations reference, adopt the disintegration time of back 4 schemes of prescription of the present invention significantly to shorten.
2, dissolution experiment: experimental result such as table 2
Choose 6 samples of dispersible tablet of the present invention, as follows according to the dissolution determination method detection of two appendix of Chinese Pharmacopoeia version in 2005.
Table 2
| Time min | 1 | 2 | 3 | 4 | 5 | 6 | On average ± SD |
| 2 | 69.59 | 68.37 | 70.22 | 7049 | 69.89 | 70.27 | 69.81％±0.77 |
| 5 | 76.28 | 75.46 | 75.33 | 76.19 | 75.47 | 75.22 | 75.66％±0.46 |
| 10 | 81.64 | 80.37 | 79.96 | 80.55 | 8146 | 79.84 | 80.64％±0.76 |
| 20 | 87.29 | 86.34 | 85.77 | 86.24 | 85.67 | 86.99 | 86.22％±0.59 |
| 30 | 90.28 | 91.37 | 91.44 | 92.09 | 90.52 | 89.37 | 90.85％±0.98 |
| 45 | 91.76 | 92.07 | 91.66 | 92.53 | 91.37 | 90.76 | 91.68％±0.60 |
| 60 | 91.38 | 93.26 | 92.57 | 91.66 | 9249 | 92.18 | 92.26％±0.68 |
Laboratory test results shows, the stripping behavior basically identical of dispersible tablet of the present invention, all disintegrates fully in a minute, dissolution is greater than 90% in the time of 45 minutes, dispersing uniformity and dissolution rate all meet the requirements, and the dissolution of commercially available ordinary tablet is about 80%.
3, lab scale data,
Table 3
| Batch | Principal agent throwing amount only | Content (%) | Dissolution (%) | Friability (%) | Product yield (%) |
| 1 | 5.00g | 99.70 | 90.42 | 0.55 | 95.8 |
| 2 | 5.00g | 99.62 | 90.91 | 0.76 | 97.3 |
| 3 | 5.00g | 99.81 | 91.06 | 0.52 | 96.1 |
The pilot scale data
Table 4
| Batch | Principal agent throwing amount only | Content (%) | Dissolution %) | Related substance (%) | Product yield (%) |
| 1 | 50.00g | 99.75 | 90.90 | 2.13 | 99.1 |
| 2 | 50.00g | 99.53 | 91.73 | 2.16 | 98.7 |
| 3 | 50.00g | 99.69 | 91.86 | 2.14 | 98.4 |
Above-mentioned experiment shows that technology stability of the present invention is good, and described dispersible tablet product property is even, and reliable in quality is fit to the commercial production of magnifying.
4, influence factor and stability experiment
(1), dispersible tablet of the present invention is at strong illumination (4500Lx ± 500Lx) investigate 10 days under the condition, the check result of every indexs such as appearance character, related substance, dissolution, content does not have obviously to change substantially, shows that character is basicly stable under the high light condition.Experimental result such as table 5
Table 5
| Time (my god) | Character | Dissolution (%) | Related substance (%) | Content (%) |
| 0 | White tablets | 90.90 | 2.13 | 99.75 |
| 5 | White tablets | 90.71 | 2.19 | 99.57 |
| 10 | White tablets | 90.66 | 2.23 | 99.51 |
(2), dispersible tablet of the present invention investigates 10 days under 60 ℃ condition, the check result of every indexs such as appearance character, related substance, dissolution, content does not have obviously to change substantially, shows that its character under hot conditions is basicly stable.Experimental result such as table 6
Table 6
| Time (my god) | Character | Dissolution (%) | Related substance (%) | Content (%) |
| 0 | White tablets | 90.90 | 2.13 | 99.75 |
| 5 | White tablets | 90.83 | 2.25 | 99.64 |
| 10 | White tablets | 91.14 | 2.31 | 99.57 |
(3), dispersible tablet of the present invention investigates 10 days under the condition of relative humidity 92.5%, except that sample moisture absorption weightening finish was big, the check result of every indexs such as related substance, dissolution, content not have obviously change substantially, illustrates that this product should seal preservation.Experimental result such as table 7
Table 7
| Time (my god) | Character | Weightening finish | Dissolution (%) | Related substance (%) | Content (%) |
| 0 | White tablets | --- | 90.90 | 2.13 | 99.75 |
| 5 | White tablets | 5.22 | 90.83 | 2.25 | 99.64 |
| 10 | White tablets | 12.26 | 91.14 | 2.31 | 99.57 |
(4), dispersible tablet of the present invention is in accelerated test (40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%) investigates 6 months under the condition, the check result of every investigation index does not have to change substantially, illustrates that this product character under temperature accelerated test condition is basicly stable.Experimental result such as table 8
Table 8
| Time (moon) | Character | Dissolution (%) | Related substance (%) | Content (%) |
| 0 | White tablets | 90.90 | 2.13 | 99.75 |
| 1 | White tablets | 91.36 | 2.25 | 99.64 |
| 2 | White tablets | 91.75 | 2.31 | 99.57 |
| 3 | White tablets | 91.79 | 2.38 | 99.66 |
| 6 | White tablets | 91.20 | 2.11 | 99.78 |
(5), dispersible tablet of the present invention investigates 12 months under long-term experiment (25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%) condition, the check result of every investigation index does not have to change substantially, this product is described, and character is basicly stable at ambient temperature.Experimental result such as table 9
Table 9
| Time (moon) | Character | Dissolution (%) | Related substance (%) | Content (%) |
| 0 | White tablets | 90.90 | 2.13 | 99.53 |
| 3 | White tablets | 91.36 | 2.50 | 99.63 |
| 6 | White tablets | 91.38 | 2.15 | 99.73 |
| 9 | White tablets | 91.39 | 2.31 | 99.71 |
| 12 | White tablets | 91.34 | 2.35 | 99.71 |
Related substance is an impurity, comprises impurities in raw materials, catabolite, and its content is few more good more.Said determination shows, compares the basic no change of the related substance in the dispersible tablet with raw material.
5, toxicity test: acute toxicity, rat oral LD
50Be 20mg/kg; Mouse peritoneal injection LD
50Be 9.1mg/kg, intravenous injection LD
50Be 6.9mg/kg.
Genotoxicity: this product zoopery does not have teratogenesis.
Lappaconitine hydrobromide dispersible tablet of the present invention relatively with existing lappaconitine hydrobromide sheet after being taken by the patient, disintegrate is fast, the dissolution height, so health can absorb rapidly, rapid-action, half an hour, took effect after common lappaconitine hydrobromide sheet was generally taken, and the Lappaconitine hydrobromide dispersible tablet that the present invention narrates can take effect in the time about 10 minutes, so can alleviate the pain perception of cancer patient or patients after surgery quickly.
The specific embodiment
Embodiment 1:
A kind of Lappaconitine hydrobromide dispersible tablet is to be made by the raw material of following weight ratio, lappaconitine hydrobromide 5g, microcrystalline Cellulose 60g, polyvinylpolypyrrolidone 30g, micropowder silica gel 10g.
Preparation method is: lappaconitine hydrobromide is pulverized, crossed 120 mesh sieves; Microcrystalline Cellulose and polyvinylpolypyrrolidone are crossed 120 mesh sieves respectively, be the polyvinylpolypyrrolidone mix homogeneously of 10g with lappaconitine hydrobromide and microcrystalline Cellulose and 1/3 weight again, cross 80 mesh sieves, make soft material in the abundant mixing of ethanol of the ratio adding 60% that mixes back gross weight 20ml/100g again, 20 mesh sieves are granulated, 60 ℃ of dryings, 20 mesh sieve granulate, add the polyvinylpolypyrrolidone of remaining 2/3 weight and micropowder silica gel mix homogeneously again, tabletting gets final product, and can be made into 1000 (5mg/ sheets).
The lappaconitine hydrobromide crude drug can be selected the product of Gansu Lanyao Pharmaceutical Industry Group Co., Ltd. for use, and by this product quality standard test, the result is that loss on drying 0.6% is calculated according to dry product, contains C
32H
44N
2O
8HBr is 96.8%, by this calculating, contains C in every 100g raw material
32H
44N
2O
8H
2O is 87.56g, so actual input material quantity is 5.710g in the embodiment sample.
Embodiment 2:
A kind of Lappaconitine hydrobromide dispersible tablet is to be made by the raw material of following weight ratio, lappaconitine hydrobromide 5g, microcrystalline Cellulose
30142g, polyvinylpolypyrrolidone 21g, micropowder silica gel 7g.
Preparation method is: lappaconitine hydrobromide is pulverized, crossed 120 mesh sieves; Microcrystalline Cellulose
301Cross 120 mesh sieves respectively with polyvinylpolypyrrolidone, be the polyvinylpolypyrrolidone mix homogeneously of 10.5g with lappaconitine hydrobromide and microcrystalline Cellulose and 1/2 weight again, cross 80 mesh sieves, make soft material in the abundant mixing of ethanol of the ratio adding 70% that mixes back gross weight 10ml/100g again, 20 mesh sieves are granulated, 60 ℃ of dryings, 20 mesh sieve granulate add the polyvinylpolypyrrolidone of remaining 1/2 weight and micropowder silica gel mix homogeneously, tabletting gets final product again.Microcrystalline Cellulose
301Be imported product.
Embodiment 3:
A kind of Lappaconitine hydrobromide dispersible tablet is to be made by the raw material of following weight ratio, lappaconitine hydrobromide 5g, microcrystalline Cellulose 78g, polyvinylpolypyrrolidone 39g, micropowder silica gel 13g.
Preparation method is: lappaconitine hydrobromide is pulverized, crossed 120 mesh sieves; Microcrystalline Cellulose and polyvinylpolypyrrolidone are crossed 120 mesh sieves respectively, be the polyvinylpolypyrrolidone mix homogeneously of 26g with lappaconitine hydrobromide and microcrystalline Cellulose and 2/3 weight again, cross 80 mesh sieves, add 80% the abundant mixing of ethanol in the ratio of the moistening said mixture gross weight 25ml/100g of want again and make soft material, 20 mesh sieves are granulated, 60 ℃ of dryings, 20 mesh sieve granulate add the polyvinylpolypyrrolidone of remaining 1/3 weight and micropowder silica gel mix homogeneously, tabletting gets final product again.
Embodiment 4:
A kind of Lappaconitine hydrobromide dispersible tablet is to be made by the raw material of following weight ratio, lappaconitine hydrobromide 5g, microcrystalline Cellulose 50g, polyvinylpolypyrrolidone 25g, micropowder silica gel 8g.
Preparation method is: lappaconitine hydrobromide is pulverized, crossed 100 mesh sieves; Microcrystalline Cellulose and polyvinylpolypyrrolidone are crossed 100 mesh sieves respectively, again with the i.e. polyvinylpolypyrrolidone mix homogeneously of about 8.3g of lappaconitine hydrobromide and microcrystalline Cellulose and 1/3 weight, cross 60 mesh sieves, add 60% the abundant mixing of ethanol in the ratio of the moistening said mixture gross weight 20ml/100g of want again and make soft material, 16 mesh sieves are granulated, 60 ℃ of dryings, 16 mesh sieve granulate, add the polyvinylpolypyrrolidone of remaining 2/3 weight and micropowder silica gel mix homogeneously again, tabletting gets final product, and can be made into 1000 (5mg/ sheets).
Embodiment 5:
A kind of Lappaconitine hydrobromide dispersible tablet is to be made by the raw material of following weight ratio, lappaconitine hydrobromide 5g, microcrystalline Cellulose 70g, polyvinylpolypyrrolidone 35g, micropowder silica gel 11g.
Lappaconitine hydrobromide is pulverized, crossed 120 mesh sieves; Microcrystalline Cellulose and polyvinylpolypyrrolidone are crossed 120 mesh sieves respectively, again with the i.e. polyvinylpolypyrrolidone mix homogeneously of about 11.7g of lappaconitine hydrobromide and microcrystalline Cellulose and 1/3 weight, cross 100 mesh sieves, add 60% the abundant mixing of ethanol in the ratio of the moistening said mixture gross weight 20ml/100g of want again and make soft material, 20 mesh sieves are granulated, can 50～70 ℃ down dry, 20 mesh sieve granulate add the polyvinylpolypyrrolidone of 2/3 remaining weight and micropowder silica gel mix homogeneously, tabletting gets final product again.
Claims (4)
1, a kind of Lappaconitine hydrobromide dispersible tablet is characterized in that: be to make by the raw material of following weight ratio, and 5 parts of lappaconitine hydrobromide, 42～78 parts of microcrystalline Cellulose, 21～39 parts of polyvinylpolypyrrolidone, 7～13 parts of micropowder silica gels.
2, Lappaconitine hydrobromide dispersible tablet according to claim 1 is characterized in that: be to make by the raw material of following weight ratio, and 5 parts of lappaconitine hydrobromide, 50～70 parts of microcrystalline Cellulose, 25～35 parts of polyvinylpolypyrrolidone, 8～11 parts of micropowder silica gels.
3, Lappaconitine hydrobromide dispersible tablet according to claim 1 is characterized in that: be to make by the raw material of following weight ratio, and 5 parts of lappaconitine hydrobromide, 60 parts of microcrystalline Cellulose, 30 parts of polyvinylpolypyrrolidone, 10 parts of micropowder silica gels.
4, a kind of preparation method of Lappaconitine hydrobromide dispersible tablet is characterized in that: the lappaconitine hydrobromide of 5 weight portions is pulverized, crossed 100～120 mesh sieves; The polyvinylpolypyrrolidone of the microcrystalline Cellulose of 42～78 weight portions and 21～39 weight portions is crossed 100～120 mesh sieves respectively, again with the polyvinylpolypyrrolidone mix homogeneously of lappaconitine hydrobromide and microcrystalline Cellulose and 1/3～2/3 weight, cross 60～100 mesh sieves, ratio in the moistening said mixture total amount 10～25ml/100g of want adds ethanol again, abundant mixing, granulate, drying adds remaining polyvinylpolypyrrolidone and 7～13 parts by weight of micro silica gel powder mix homogeneously, tabletting gets final product again.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100124512A CN100525765C (en) | 2006-02-24 | 2006-02-24 | Lappaconitine hydrobromide dispersible tablet and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100124512A CN100525765C (en) | 2006-02-24 | 2006-02-24 | Lappaconitine hydrobromide dispersible tablet and its preparing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1850077A CN1850077A (en) | 2006-10-25 |
| CN100525765C true CN100525765C (en) | 2009-08-12 |
Family
ID=37131589
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100124512A Expired - Fee Related CN100525765C (en) | 2006-02-24 | 2006-02-24 | Lappaconitine hydrobromide dispersible tablet and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100525765C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102178658B (en) * | 2011-05-03 | 2013-04-10 | 中国人民解放军第三军医大学第二附属医院 | Lappaconitine hydrobromide orally disintegrating tablets and preparation method thereof |
-
2006
- 2006-02-24 CN CNB2006100124512A patent/CN100525765C/en not_active Expired - Fee Related
Non-Patent Citations (4)
| Title |
|---|
| 分散片制备技术. 陈志明，陆伟根，王大林.中国医药工业杂志，第35卷第6期. 2004 |
| 分散片制备技术. 陈志明，陆伟根，王大林.中国医药工业杂志，第35卷第6期. 2004 * |
| 现代临床药物大典. 罗明生等，217，四川科学技术出版社. 2001 |
| 现代临床药物大典. 罗明生等，217，四川科学技术出版社. 2001 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1850077A (en) | 2006-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103301084B (en) | Berberine hydrochloride tablet and preparation method thereof | |
| Chowdary et al. | Recent research on co-processed excipients for direct compression-A Review | |
| CN102552258A (en) | Pharmaceutical composition containing repaglinide and preparation method of same | |
| CN101695480A (en) | Olopatadine hydrochloride dispersible tablets, preparation method thereof and quality control method thereof | |
| CN105456270A (en) | Dipeptidyl peptidase IV inhibitor pharmaceutical composition, use and preparation method thereof | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| CN103356616A (en) | Bilastine-containing pharmaceutical composition and preparation method thereof | |
| KR20090037435A (en) | Tablet composition containing chinese herb extract | |
| CN101653425B (en) | Arbidol hydrochloride medicament composition dispersible tablets and preparation method thereof | |
| CN103251569B (en) | Capecitabine tablet composition and preparation method thereof | |
| CN101167731A (en) | Dispersible tablet containing metformin and glibenclamide and preparation method thereof | |
| CN100525765C (en) | Lappaconitine hydrobromide dispersible tablet and its preparing method | |
| CN101683325A (en) | Cydiodine buccal tablets and preparation method thereof | |
| CN102114009A (en) | Pharmaceutical composition containing tomoxetine and preparation method thereof | |
| WO2013177833A1 (en) | Dysmenorrhea-treating medicament and preparation method therefor | |
| CN103284953A (en) | Bicyclol solid preparation and preparation method thereof | |
| CN102935073B (en) | Glimepiride dispersible tablet and preparation method thereof | |
| CN101991859A (en) | Beta-cyclodextrin inclusion compound of huperzine A, and preparation method and preparation thereof | |
| CN101485673B (en) | Roxithromycin and ambroxol hydrochloride dispersible tablets | |
| CN104224783A (en) | Medicine composition containing repaglinide and metformin and preparation method of medicine composition | |
| CN103655645A (en) | Chinese buckeye seed extract tablets and preparation method thereof | |
| CN103919739B (en) | A kind of repaglinide compressed tablets and preparation method thereof | |
| CN110934872B (en) | Levohydroxyeugenol capsule and preparation method thereof | |
| CN102600093A (en) | Moxifloxacin tablet and preparation method thereof | |
| KR100788454B1 (en) | Rapid-acting fomulation containing nateglinide as an active ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090812 Termination date: 20120224 |