CN104721207A - Drug composition - Google Patents
Drug composition Download PDFInfo
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- CN104721207A CN104721207A CN201410350801.0A CN201410350801A CN104721207A CN 104721207 A CN104721207 A CN 104721207A CN 201410350801 A CN201410350801 A CN 201410350801A CN 104721207 A CN104721207 A CN 104721207A
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- Prior art keywords
- liquirtin
- monohydrate
- compositions described
- pvp
- mannitol
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Abstract
The invention provides a drug composition and relates to a preparation composition containing liquiritin monohydrate, belonging to the technical field of drugs. Applications of liquiritin to drugs for resisting myocardial ischemia and reperfusion arrhythmia and resisting myocardial ischemia caused by isoprenaline are disclosed in Chinese patents 200610016770.0 and 200610016771 respectively. Due to technical problems, safe and effective liquiritin preparations suitable for human to take orally have not come out. The invention provides a safe and effective liquiritin oral preparation. The liquiritin composition contains 45-71.1% of liquiritin monohydrate, and when the mass percentage of croscarmellose sodium is 3-9.2%, the mass percentage of water soluble auxiliary materials is 6-35%.
Description
Technical field
the present invention relates to a kind of preparation compositions containing liquirtin monohydrate, belong to medical art.
Background technology
in recent years, cardiovascular and cerebrovascular disease has become the number one killer threatening healthy elder and longevity, is one of large causes of death of the mankind three.Cardiovascular and cerebrovascular disease needs long-term prescription, and Western medicine always also exists various side effect, and long-term taking has certain infringement to human body.Therefore, the medicine finding safe and effective treatment cardiovascular and cerebrovascular disease becomes current study hotspot.
chinese patent 200610016770.0 discloses liquirtin in the application of filling with again in arrhythmia medicine that resists myocardial ischemia; 200610016771 disclose the application in the myocardial ischemia drug that liquirtin causes at anti-isoproterenol.Radix Glycyrrhizae is Chinese medicine, now large area artificial growth, develops fully, this medical material can be made to be fully utilized, open up new application market it, has castering action to the plantation of medical material, production, processing and related industry.Meanwhile, from Chinese medicine, find cardiovascular drugs and also there is good Social benefit and economic benefit.
liquirtin prepared by existing alcohol extraction or extraction process by water exists with the form of liquirtin monohydrate.Liquirtin monohydrate (molecular formula: C
21
h
22
o
9
h
2
o) can be obtained by extracting in the dry root and rhizome of pulse family Glycyrrhiza various plants glycyrrhizic legume, Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L., belong to flavonoid glycoside.Liquirtin is dissolved in methanol, ethanol, dilute sodium hydroxide, is insoluble in water, and viscosity is large, easy balling.
although existing knowledge discloses the medical usage of liquirtin and liquirtin, the application of this project only rests on the in vitro tests stage, and due to technical problem, the safe and effective liquiritin preparation being applicable to the mankind oral never emerges.
the technical problem to be solved in the present invention solves the low problem of liquirtin oral formulations dissolution, and the problem of slice, thin piece poor compressibility.A kind of safe and effective liquirtin oral formulations is provided for clinical.
Summary of the invention
the object of this invention is to provide a kind of safe and effective liquirtin oral formulations; Another object of the present invention is to provide a kind of liquirtin compositions of high-dissolution; Another object of the present invention solves liquirtin tablet compressibility and friability problem.
the present composition because of specification large, production technology and finished product acceptor medicine characteristics influence are comparatively large, and especially tablet exists unilateral unsmooth, poor compressibility and the high problem of friability, meanwhile, also there is dissolution rate slow, the problem that dissolution is low in tablet.
through a series of prescription screening, the present inventor finds: when to account for composition weight percent be 3%-9.2% to the weight of cross-linking sodium carboxymethyl cellulose in prescription, and when the weight of water soluble adjuvant accounts for the 6%-35% of pharmaceutical composition percetage by weight, the dissolubility of active component improves greatly.
technical scheme of the present invention is: a kind of liquirtin compositions, it is characterized in that containing liquirtin monohydrate 45% ~ 71.1%, and when cross-linking sodium carboxymethyl cellulose is 3%-9.2%, water soluble adjuvant is 6%-35%, and described percentage ratio is mass percent.
the preferred technical scheme of the present invention, containing liquirtin monohydrate 100 ~ 300mg in compositions.
the preferred technical scheme of the present invention, D90≤10 μm of liquirtin monohydrate in compositions.More preferably D90≤8 μm.
the preferred technical scheme of the present invention is:
a kind of liquirtin compositions, is characterized in that the liquirtin monohydrate 45% ~ 71% containing D90≤10um, mannitol 4.5% ~ 32%, microcrystalline Cellulose 4.5% ~ 32%.
the preferred technical scheme of the present invention, also containing cross-linking sodium carboxymethyl cellulose 3% ~ 9.2%, surfactant 0.3% ~ 1%.
the preferred technical scheme of the present invention, described surfactant is selected from sodium lauryl sulphate.
the preferred technical scheme of the present invention, also containing aerosil 1%, magnesium stearate 1%.
above percentage ratio is mass percent.
the preferred technical scheme of the present invention is: a kind of pharmaceutical composition, it is characterized in that, every 1000 contain liquirtin monohydrate 100 ~ 300 g(D90≤10um), mannitol 70g, microcrystalline Cellulose 20g, sodium lauryl sulphate 1.35g, PVP K30 5g, cross-linking sodium carboxymethyl cellulose 20g, aerosil 2.17 ~ 4.20g, magnesium stearate 2.17 ~ 4.20g.
the preferred technical scheme of the present invention is a kind of liquirtin monohydrate compositions, it is characterized in that, every 1000 contain liquirtin monohydrate 150g(D90≤8um), mannitol 45g, microcrystalline Cellulose 45g, sodium lauryl sulphate 1.35g, PVP K30 5g, cross-linking sodium carboxymethyl cellulose 20g, aerosil 2.60g, magnesium stearate 2.60g.
the preferred technical scheme of the present invention, described surfactant can also be non-ionic surface active agent polyethylene glycols, Tweens.
the preparation method of the present invention's benefit heart element sheet, is characterized in that:
the first step adopts jet mill that liquirtin monohydrate is micronized to D90≤10um.
second step takes recipe quantity PVP K30 and adds in purified water, and be mixed with 10% PVP K30 aqueous solution (W/W), stirring and dissolving is to mix homogeneously, for subsequent use.
the aerosil (inside adding) of liquirtin monohydrate, mannitol, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate and 1/2nd recipe quantities prepared by the first step that the 3rd step takes recipe quantity.
load weighted material is placed in wet mixing pelletizer, mix homogeneously by the 4th step, adds 10% polyvidone k30 aqueous solution of recipe quantity, mix homogeneously, and 24 mesh sieves are granulated.
5th step wet granular is 40 ~ 50 DEG C of dryings in baking oven.
the aerosil (additional) of dry material and 1/2nd recipe quantities drops in oscillating granulator, with 24 eye mesh screen granulate by the 6th step.
the magnesium stearate of the granule that the 7th step the 6th step obtains and recipe quantity joins in three-dimensional motion mixer, mix homogeneously.
8th step tabletting.
the beneficial effect of the present composition:
by rational compatibility and PROCESS FOR TREATMENT, the present composition overcomes because specification is large, finished product quality acceptor property of medicine matter and state affect large problem, overcome the difficult problem that prior art exists, and provide a kind of stable, safe oral tablet compositions for clinical.
the present composition is 2 times/day, 1 piece/times.
embodiment 1, liquirtin monohydrate 100g(D90≤10um), mannitol 70g, microcrystalline Cellulose 20g, sodium lauryl sulphate 1.35g, 10% PVP K30 aqueous solution 50g, cross-linking sodium carboxymethyl cellulose 20g, aerosil 2.62g, magnesium stearate 2.62g.1000 are prepared by the preparation method of technical scheme part.
embodiment 2, liquirtin monohydrate 150g(D90≤8um), mannitol 45g, microcrystalline Cellulose 45g, sodium lauryl sulphate 1.35g, 10% PVP K30 aqueous solution 50g, cross-linking sodium carboxymethyl cellulose 10g, aerosil 2.71g, magnesium stearate 2.71g.1000 are prepared by the preparation method of technical scheme part.
embodiment 3, prescription with embodiment 2, but adopt 3% hydroxypropyl methylcellulose E5 aqueous solution to be binding agent.1000 are prepared by the preparation method of technical scheme part.
embodiment 4, liquirtin monohydrate 300g(D90≤8um), mannitol 70g, microcrystalline Cellulose 20g, sodium lauryl sulphate 1.35g, 10% PVP K30 aqueous solution 55g, cross-linking sodium carboxymethyl cellulose 20 g, aerosil 4.20g, magnesium stearate 4.20g.1000 are prepared by the preparation method of technical scheme part.
reference examples 1, prescription are with embodiment 1, but liquirtin monohydrate D90=13 ~ 26um.
reference examples 2, prescription with embodiment 1, but do not add surfactant sodium hexadecyl sulfate.
reference examples 3, prescription with embodiment 1, but adopt purified water to replace 10% PVP K30 aqueous solution to be binding agent.
reference examples 4, liquirtin monohydrate 100g, lactose 68g, starch 60 g, Pulvis Talci 20g.Take method for preparing tablet thereof well-known in the art, in appropriate vessel, mix all components, make granule, then add magnesium stearate 2g, mixing, tabletting, prepares 1000.
test example 1: by 2010 editions pharmacopeia, annex XC second method, measure the dissolution of embodiment 1 to 4 and reference examples 1 to 4 product, data are recorded in table 1.
table 1. dissolution comparative test result (medium is water)
table 1 data illustrate: 60 minutes dissolutions of embodiment 1 ~ 4 product, apparently higher than reference examples 1 ~ 4, illustrate that the present composition solves the low problem of dissolution.
test example 2 observes the outward appearance of embodiment 1-4 and reference examples 1-4 sheet, is recorded in table 2.
table 2
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Reference examples 1 | Reference examples 2 | Reference examples 3 | Reference examples 4 | |
| Sheet outward appearance | Smooth | Smooth | Smooth | Smooth | There is pit | There is pit | Sticking, spottiness | There is pit |
table 2 data illustrate, the outward appearance of embodiment of the present invention 1-4 product is significantly better than the outward appearance of reference examples 1-4 product.
test example 3: the highest hardness measuring embodiment 1 ~ 4 product and reference examples 1 ~ 4 product, by 2010 editions pharmacopeia, annex XG method measures tablet friability, and data are recorded in table 3
table 3. compressibility and friability test result
in table 3, data illustrate: 1, under the same operating conditions, the slice, thin piece outward appearance of embodiment 1 ~ 4, significantly better than reference examples 1-4, illustrates that the compressibility of technical solution of the present invention is better than reference examples 1 ~ 4.
, embodiment 1 ~ 4 friability numerical value be starkly lower than reference examples 1-4.Illustrate embodiment of the present invention slice, thin piece be impacted after slice, thin piece weight and outward appearance substantially do not change.
to sum up, technical solution of the present invention reaches object, provides a kind of stable, safe oral formulations for clinical.
Claims (8)
1. a liquirtin compositions, is characterized in that, containing liquirtin monohydrate 45% ~ 71.1%, during cross-linking sodium carboxymethyl cellulose 3%-9.2%, water soluble adjuvant 6%-35%, described percentage ratio is mass percent.
2. compositions described in claim 1, is characterized in that, containing liquirtin monohydrate 100 ~ 300mg.
3. compositions described in claim 1, is characterized in that, the D90 of liquirtin monohydrate is≤10 μm.
4. compositions described in claim 1, is characterized in that, the D90 of liquirtin monohydrate is≤8 μm.
5. compositions described in claim 1, is characterized in that, the liquirtin monohydrate 45% ~ 71% containing D90≤10um, mannitol 4.5% ~ 32%, microcrystalline Cellulose 4.5% ~ 32%.
6. compositions described in claim 1, is characterized in that, every 1000 liquirtin monohydrate 100 ~ 300 g containing D90≤10um, mannitol 70g, microcrystalline Cellulose 20g, sodium lauryl sulphate 1.35g, PVP K30 5g, cross-linking sodium carboxymethyl cellulose 20g.
7. compositions described in claim 1, is characterized in that, every 1000 liquirtin monohydrate 150g containing D90≤8um, mannitol 45g, microcrystalline Cellulose 45g, sodium lauryl sulphate 1.35g, PVP K30 5g, cross-linking sodium carboxymethyl cellulose 20g.
8. the preparation method of compositions described in claim 1, is characterized in that,
The first step adopts jet mill that liquirtin monohydrate is micronized to D90≤10um;
Second step takes recipe quantity PVP K30 and adds in purified water, and be mixed with 10% PVP K30 aqueous solution (W/W), stirring and dissolving is to mix homogeneously, for subsequent use;
The aerosil of liquirtin monohydrate, mannitol, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate and 1/2nd recipe quantities prepared by the first step that the 3rd step takes recipe quantity;
Load weighted material is placed in wet mixing pelletizer, mix homogeneously by the 4th step, adds 10% polyvidone k30 aqueous solution of recipe quantity, mix homogeneously, and 24 mesh sieves are granulated;
5th step wet granular is 40 ~ 50 DEG C of dryings in baking oven;
The aerosil of dry material and 1/2nd recipe quantities drops in oscillating granulator, with 24 eye mesh screen granulate by the 6th step;
The magnesium stearate of the granule that the 7th step the 6th step obtains and recipe quantity joins in three-dimensional motion mixer, mix homogeneously;
8th step tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410350801.0A CN104721207B (en) | 2014-07-23 | 2014-07-23 | A kind of pharmaceutical composition |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410350801.0A CN104721207B (en) | 2014-07-23 | 2014-07-23 | A kind of pharmaceutical composition |
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| CN104721207A true CN104721207A (en) | 2015-06-24 |
| CN104721207B CN104721207B (en) | 2019-03-05 |
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| CN201410350801.0A Expired - Fee Related CN104721207B (en) | 2014-07-23 | 2014-07-23 | A kind of pharmaceutical composition |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107714667A (en) * | 2017-11-20 | 2018-02-23 | 威海贯标信息科技有限公司 | A kind of Dapagliflozin agent composition |
| CN107744512A (en) * | 2017-12-04 | 2018-03-02 | 威海贯标信息科技有限公司 | A kind of canagliflozin composition |
| CN107811983A (en) * | 2017-12-04 | 2018-03-20 | 威海贯标信息科技有限公司 | A kind of tofogliflozin composition |
| CN107898764A (en) * | 2017-12-12 | 2018-04-13 | 威海贯标信息科技有限公司 | A kind of net compositions of Ai Gelie |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101032505A (en) * | 2006-04-17 | 2007-09-12 | 李超生 | Treatment medicine and healthy product including liquiritin |
| CN101032504A (en) * | 2006-04-17 | 2007-09-12 | 李超生 | Application of liquiritin in medicines |
| CN101518542A (en) * | 2009-04-07 | 2009-09-02 | 浙江大学 | Liquiritin preparation and application thereof |
-
2014
- 2014-07-23 CN CN201410350801.0A patent/CN104721207B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101032505A (en) * | 2006-04-17 | 2007-09-12 | 李超生 | Treatment medicine and healthy product including liquiritin |
| CN101032504A (en) * | 2006-04-17 | 2007-09-12 | 李超生 | Application of liquiritin in medicines |
| CN101518542A (en) * | 2009-04-07 | 2009-09-02 | 浙江大学 | Liquiritin preparation and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 刘建平: "《生物药剂学与药物动力学》", 31 August 2011, 人民卫生出版社 * |
| 王宝瑄: "《有机化学词典》", 30 June 1987, 科学出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107714667A (en) * | 2017-11-20 | 2018-02-23 | 威海贯标信息科技有限公司 | A kind of Dapagliflozin agent composition |
| CN107744512A (en) * | 2017-12-04 | 2018-03-02 | 威海贯标信息科技有限公司 | A kind of canagliflozin composition |
| CN107811983A (en) * | 2017-12-04 | 2018-03-20 | 威海贯标信息科技有限公司 | A kind of tofogliflozin composition |
| CN107898764A (en) * | 2017-12-12 | 2018-04-13 | 威海贯标信息科技有限公司 | A kind of net compositions of Ai Gelie |
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| CN104721207B (en) | 2019-03-05 |
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| C06 | Publication | ||
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| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20160623 Address after: Economic and Technological Development Zone of Shandong Province, Weihai City, Gushan Town, 264205 No. 18 South Road, No. 19 North Road, No. 3 East Road, the west five Applicant after: Weihai Disu Pharmaceutical Co., Ltd. Applicant after: Disha Pharmaceutical Industry Group Corp., Ltd. Address before: 264205, Weihai economic and Technological Zone, Shandong Province, Qingdao South Road, No. 1 Applicant before: Disha Pharmaceutical Industry Group Corp., Ltd. Applicant before: WEIHAI DIJIA PHARMACEUTICAL CO., LTD. |
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| TR01 | Transfer of patent right |
Effective date of registration: 20191107 Address after: 264205 Guangzhou East Road South and an East Road East, Wendeng economic and Technological Development Zone, Weihai City, Shandong Province Co-patentee after: Weihai Disu Pharmaceutical Co., Ltd. Patentee after: Dijia Pharmaceutical Group Co., Ltd Co-patentee after: Disha Pharmaceutical Industry Group Corp., Ltd. Address before: Economic and Technological Development Zone of Shandong Province, Weihai City, Gushan Town, 264205 No. 18 South Road, No. 19 North Road, No. 3 East Road, the west five Co-patentee before: Disha Pharmaceutical Industry Group Corp., Ltd. Patentee before: Weihai Disu Pharmaceutical Co., Ltd. |
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| TR01 | Transfer of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20190305 Termination date: 20200723 |
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| CF01 | Termination of patent right due to non-payment of annual fee |