CN103099796A - Propylene glycol marinate sulfate-containing sustained-release preparation and preparation method thereof - Google Patents
Propylene glycol marinate sulfate-containing sustained-release preparation and preparation method thereof Download PDFInfo
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- CN103099796A CN103099796A CN2013100536300A CN201310053630A CN103099796A CN 103099796 A CN103099796 A CN 103099796A CN 2013100536300 A CN2013100536300 A CN 2013100536300A CN 201310053630 A CN201310053630 A CN 201310053630A CN 103099796 A CN103099796 A CN 103099796A
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- sugar ester
- slow releasing
- preparation
- releasing preparation
- glycosides sugar
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- 238000002360 preparation method Methods 0.000 title claims abstract description 68
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 title abstract 15
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 title abstract 5
- 239000003405 delayed action preparation Substances 0.000 title abstract 4
- 239000011159 matrix material Substances 0.000 claims abstract description 26
- 238000013268 sustained release Methods 0.000 claims abstract description 21
- 239000012730 sustained-release form Substances 0.000 claims abstract description 21
- 239000000945 filler Substances 0.000 claims abstract description 10
- 239000000314 lubricant Substances 0.000 claims abstract description 10
- 239000004094 surface-active agent Substances 0.000 claims abstract description 5
- 150000002148 esters Chemical class 0.000 claims description 45
- 229930182470 glycoside Natural products 0.000 claims description 45
- 150000002338 glycosides Chemical class 0.000 claims description 45
- 239000000758 substrate Substances 0.000 claims description 20
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 15
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 15
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 15
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 15
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 15
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 239000007767 bonding agent Substances 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 5
- 239000012467 final product Substances 0.000 claims description 5
- 229920000609 methyl cellulose Polymers 0.000 claims description 5
- 239000001923 methylcellulose Substances 0.000 claims description 5
- 235000010981 methylcellulose Nutrition 0.000 claims description 5
- -1 polyoxyethylene Polymers 0.000 claims description 5
- 239000007779 soft material Substances 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 229920002261 Corn starch Polymers 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 241000196324 Embryophyta Species 0.000 claims description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 239000008120 corn starch Substances 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 125000005456 glyceride group Chemical group 0.000 claims description 2
- 229940074046 glyceryl laurate Drugs 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 9
- 239000011230 binding agent Substances 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 6
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229920000985 (beta-D-Mannuronate)n Polymers 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a propylene glycol marinate sulfate sustained-release preparation and a preparation method thereof. The propylene glycol marinate sulfate sustained-release preparation comprises: propylene glycol marinate sulfate, a sustained-release skeleton matrix, a filler, a surfactant, a lubricant and a binder. The propylene glycol marinate sulfate sustained-release preparation disclosed in the invention can achieve long-acting release, and can release drug ingredients stably and evenly within 24h.
Description
Technical field
The present invention relates to the slow releasing preparation agent, relate in particular to glycosides sugar ester slow releasing preparation and preparation method thereof, belong to glycosides sugar ester slow releasing preparation field.
Background technology
Mannose ester is the sodium sulfate salt of the polymannuronate propyl ester that sodium alginate is hydrolyzed, esterification forms, and belongs to blood fat reducing, antithrombotic marine drug, is used for the treatment of hyperlipemia.
Slow releasing preparation can be stablized blood drug level after administration, reduces the incidence rate of untoward reaction, improves the safety of medication.
Existing glycosides sugar ester slow releasing preparation can not discharge the glycosides sugar ester stably in 24 hours, can not reach the effect of slow release, balanced administration, had much room for improvement.
Summary of the invention
One of purpose of the present invention is to provide a kind of glycosides sugar ester slow releasing preparation of safe, steady in 24 hours, balanced release of active ingredients;
Two of purpose of the present invention is to provide a kind of method for preparing described glycosides sugar ester slow releasing preparation.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
A kind of glycosides sugar ester slow releasing preparation comprises: glycosides sugar ester and pharmaceutical adjunct; Described pharmaceutical adjunct comprises: filler, sustained-release matrix substrate, surfactant, lubricant and bonding agent.
By weight, the consumption of each composition is preferably:
Preferred, the consumption of each composition is:
Described sustained-release matrix substrate is selected from one or more in polyvinylpyrrolidone, methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose or polyoxyethylene.The kind of sustained-release matrix substrate and the selection of consumption are directly connected to the speed of drug release and even the stability of preparation, the inventor finally determines by a large amount of tests, sustained-release matrix substrate is comprised of polyvinylpyrrolidone and hydroxypropyl cellulose, especially the sustained-release matrix substrate that will be both forms according to the part by weight of the 2:1 of institute, drug release is the most steady, blood concentration fluctuation is minimum, can discharge stably in 24 hours, has best slow release effect.
Described surfactant is preferably sodium lauryl sulphate, Tween-80, poloxamer, Polyethylene Glycol caprylin, Polyethylene Glycol certain herbaceous plants with big flowers acid glyceride, Polyethylene Glycol glyceryl laurate ester or Polyethylene Glycol tristerin.
Described filler can be lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine;
Described lubricant is magnesium stearate or Pulvis Talci; Described bonding agent is that concentration is the ethanol more than 90%.
Desired another technical problem of the present invention is to provide a kind of method for preparing described glycosides sugar ester slow releasing preparation, comprises the following steps: with glycosides sugar ester, filler and slow release skeletal matrix mix homogeneously; Add bonding agent, soft material processed, drying is granulated; Add lubricant, mix homogeneously, tabletting, and get final product.
Glycosides sugar ester slow releasing preparation drug release of the present invention is steady, and blood concentration fluctuation is little, and can be in 24 hours steady, balanced release of active ingredients has slow release effect preferably.
The specific embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage and disadvantage of the present invention will be more clear along with description.But these embodiment are only exemplary, scope of the present invention are not consisted of any restriction.It will be understood by those skilled in the art that lower without departing from the spirit and scope of the present invention and can modify or replace details and the form of technical solution of the present invention, but these modifications and replacement all fall within the scope of protection of the present invention.
The preparation of embodiment 1 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
With glycosides sugar ester, filler and slow release skeletal matrix mix homogeneously; Add bonding agent, soft material processed, drying is granulated; Add again lubricant, mix homogeneously, tabletting, and get final product.
The preparation of embodiment 2 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
+ with glycosides sugar ester, filler and slow release skeletal matrix methylcellulose mix homogeneously; Add bonding agent, soft material processed, drying is granulated; Add again lubricant, mix homogeneously, tabletting, and get final product.
The preparation of embodiment 3 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
With glycosides sugar ester, filler and slow release skeletal matrix hydroxypropyl cellulose mix homogeneously; Add bonding agent, soft material processed, drying is granulated; Add again lubricant, mix homogeneously, tabletting, and get final product.
The preparation of embodiment 4 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 1:1 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 5 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 2:1 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 6 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 3:1 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 7 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 4:1 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 8 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 5:1 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 9 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 1:2 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 10 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 1:3 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 11 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 1:4 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 12 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 1:5 part by weight polyvinylpyrrolidone and hydroxypropyl cellulose;
Preparation method is with embodiment 1
The preparation of embodiment 13 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 2:1 part by weight polyvinylpyrrolidone and methylcellulose;
Preparation method is with embodiment 1.
The preparation of embodiment 14 glycosides sugar ester slow releasing preparation
Take each component by following weight portion:
Sustained-release matrix substrate is comprised of according to the 2:1 part by weight hydroxypropyl methylcellulose and methylcellulose;
Preparation method is with embodiment 1.
The drug release determination test of test example 1 glycosides sugar ester slow releasing preparation
According to drug release determination method (with reference to 2000 editions two appendix XD first methods of Chinese Pharmacopoeia), adopt dissolution method (2000 editions two appendix XC first methods of Chinese Pharmacopoeia), measure the dissolution of the prepared slow releasing preparation glycosides sugar ester in 24 hours of embodiment 1-14.Result of the test sees Table 1.
Table 1 Dissolution Rate Testing result
| ? | 1 hour | 4 hours | 8 hours | 12 hours | 16 hours | 20 hours | 24 hours |
| Embodiment 1 | 35％ | 58％ | 84％ | 100.1％ | ? | ? | ? |
| Embodiment 2 | 32％ | 54％ | 81％ | 101.2％ | ? | ? | ? |
| Embodiment 3 | 27％ | 46％ | 68％ | 89％ | 100％ | ? | ? |
| Embodiment 4 | 22％ | 45％ | 66％ | 83％ | 94％ | 100.2％ | ? |
| Embodiment 5 | 12％ | 24％ | 36％ | 55％ | 72％ | 85％ | 100.2％ |
| Embodiment 6 | 24％ | 35％ | 61％ | 82％ | 93％ | 100.2％ | ? |
| Embodiment 7 | 25％ | 41％ | 63％ | 85％ | 94％ | 100％ | ? |
| Embodiment 8 | 26％ | 45％ | 65％ | 86％ | 95％ | 100.2％ | ? |
| Embodiment 9 | 31％ | 52％ | 76％ | 93％ | 100.3％ | ? | ? |
| Embodiment 10 | 29％ | 50％ | 71％ | 87％ | 96％ | 100.3％ | ? |
| Embodiment 11 | 32％ | 49％ | 78％ | 91％ | 100.5％ | ? | ? |
| Embodiment 12 | 31％ | 43％ | 69％ | 84％ | 94％ | 100.2 | ? |
| Embodiment 13 | 34％ | 56％ | 81％ | 100％ | ? | ? | ? |
| Embodiment 14 | 37％ | 59％ | 86％ | 100.2％ | ? | ? | ? |
From result of the test as seen, glycosides sugar ester slow releasing preparation of the present invention can discharge the glycosides sugar ester stably, and wherein, the release glycosides sugar ester that the prepared slow releasing preparation of embodiment 5 is can be in 24 hours steady, balanced has best slow release effect.
Claims (9)
1. a glycosides sugar ester slow releasing preparation, is characterized in that, comprising: glycosides sugar ester and pharmaceutical adjunct; Described pharmaceutical adjunct comprises: filler, sustained-release matrix substrate, surfactant, lubricant and bonding agent.
2. according to glycosides sugar ester slow releasing preparation claimed in claim 1, it is characterized in that, by weight, the consumption of each composition is:
3. according to glycosides sugar ester slow releasing preparation claimed in claim 2, it is characterized in that, the consumption of each composition is:
4. according to any one described glycosides sugar ester slow releasing preparation of claim 1-3, it is characterized in that: described sustained-release matrix substrate is selected from one or more in polyvinylpyrrolidone, methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose or polyoxyethylene.
5. according to glycosides sugar ester slow releasing preparation claimed in claim 4, it is characterized in that: described sustained-release matrix substrate is comprised of polyvinylpyrrolidone and hydroxypropyl cellulose.
6. according to glycosides sugar ester slow releasing preparation claimed in claim 5, it is characterized in that: described sustained-release matrix substrate is comprised of polyvinylpyrrolidone and the hydroxypropyl cellulose part by weight according to 2:1.
7. according to any one described glycosides sugar ester slow releasing preparation of claim 1-3, it is characterized in that: described surfactant is sodium lauryl sulphate, Tween-80, poloxamer, Polyethylene Glycol caprylin, Polyethylene Glycol certain herbaceous plants with big flowers acid glyceride, Polyethylene Glycol glyceryl laurate ester or Polyethylene Glycol tristerin.
8. according to any one described glycosides sugar ester slow releasing preparation of claim 1-3, it is characterized in that: described filler is lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine; Described lubricant is magnesium stearate or Pulvis Talci; Described bonding agent is that concentration is the ethanol more than 90%.
9. a method for preparing any one described glycosides sugar ester slow releasing preparation of claim 1-3, comprise the following steps: with glycosides sugar ester, filler and slow release skeletal matrix mix homogeneously; Add bonding agent, soft material processed, drying is granulated; Add lubricant, mix homogeneously, tabletting, and get final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310053630.0A CN103099796B (en) | 2013-02-19 | 2013-02-19 | Propylene glycol marinate sulfate-containing sustained-release preparation and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310053630.0A CN103099796B (en) | 2013-02-19 | 2013-02-19 | Propylene glycol marinate sulfate-containing sustained-release preparation and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103127020A (en) * | 2013-02-19 | 2013-06-05 | 青岛正大海尔制药有限公司 | Alfacalcidol sustained-release preparation and preparation method thereof |
| CN105395499A (en) * | 2015-12-07 | 2016-03-16 | 青岛正大海尔制药有限公司 | Stable mannose ester tablet and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103127020A (en) * | 2013-02-19 | 2013-06-05 | 青岛正大海尔制药有限公司 | Alfacalcidol sustained-release preparation and preparation method thereof |
| CN103127020B (en) * | 2013-02-19 | 2014-07-23 | 青岛正大海尔制药有限公司 | Alfacalcidol sustained-release preparation and preparation method thereof |
| CN105395499A (en) * | 2015-12-07 | 2016-03-16 | 青岛正大海尔制药有限公司 | Stable mannose ester tablet and preparation method thereof |
| CN105395499B (en) * | 2015-12-07 | 2019-02-15 | 正大制药（青岛）有限公司 | A kind of stable glyceride tablet and preparation method thereof |
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| Publication number | Publication date |
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| CN103099796B (en) | 2014-06-25 |
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