CN104258403B - A kind of Cilostazol compositionss and preparation method thereof - Google Patents
A kind of Cilostazol compositionss and preparation method thereof Download PDFInfo
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- CN104258403B CN104258403B CN201410505685.5A CN201410505685A CN104258403B CN 104258403 B CN104258403 B CN 104258403B CN 201410505685 A CN201410505685 A CN 201410505685A CN 104258403 B CN104258403 B CN 104258403B
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- cilostazol
- ethanol
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- proline
- sodium stearyl
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Abstract
The invention provides a kind of have Cilostazol compositionss of higher oral administration biaavailability and preparation method thereof.The Cilostazol compositionss of the present invention are it is characterised in that contain Cilostazol, sodium stearyl fumarate and proline；The mass ratio of Cilostazol, sodium stearyl fumarate and proline is preferably 1:1:1.The method of Cilostazol compositionss of the present invention, its preparation process is as follows：Proline ethanol is dissolved, is subsequently adding sodium stearyl fumarate, obtains adjuvant dispersion liquid；Cilostazol ethanol is dissolved, obtains drug susbstance dispersion；By adjuvant dispersion liquid and drug susbstance dispersion mix homogeneously, reclaim ethanol, be dried, obtain final product.
Description
Technical field
The present invention relates to a kind of Cilostazol compositionss and preparation method thereof, belong to pharmaceutical technology field.
Background technology
The ischemias such as ulcer, acroesthesia, creeping chill and the intermittent claudication that Cilostazol improvement is caused due to chronic arteria occlusion disease
Property symptom etc. has significant effect, but leads to oral administration biaavailability very low due to being insoluble in water.
Content of the invention
It is an object of the invention to provide a kind of Cilostazol compositionss with higher oral administration biaavailability and its preparation
Method.
For foregoing invention purpose, the present invention provides technical scheme below：
The Cilostazol compositionss of the present invention are it is characterised in that contain Cilostazol, sodium stearyl fumarate and proline；West
Lip river he be preferably 1 by the mass ratio of azoles, sodium stearyl fumarate and proline:1:1.
The method of Cilostazol compositionss of the present invention, its preparation process is as follows：
Proline ethanol is dissolved, is subsequently adding sodium stearyl fumarate, obtains adjuvant dispersion liquid；By Cilostazol second
Alcohol dissolves, and obtains drug susbstance dispersion；By adjuvant dispersion liquid and drug susbstance dispersion mix homogeneously, reclaim ethanol, be dried, obtain final product.
Beneficial effects of the present invention are mainly：
The compositionss of the present invention significantly improve the oral administration biaavailability of Cilostazol.The compositionss preparation side of the present invention
Method is simple, low cost, is suitable to prepare with scale.The preparation method of composition of the present invention is unique, is the accident in many experiments
Find, the dispersion order of adjuvant and medicine and ratio all can not adjust.Composition, ratio and interpolation that therefore the present invention adopts are suitable
Sequence, is the innovative point of the present invention.
Specific embodiment
With reference to embodiment, the present invention is described in further detail, but it should be noted that the scope of the present invention is not subject to this
Any restriction of a little examples.
Embodiment 1
Proline 0.1g is dissolved in the ethanol of 100mL, is subsequently adding sodium stearyl fumarate 0.1g, obtain adjuvant dispersion
Liquid；Cilostazol 0.1g 50mL ethanol is dissolved, obtains drug susbstance dispersion；Adjuvant dispersion liquid and drug susbstance dispersion are mixed all
Even, 40 DEG C of vacuum reclaim ethanol, and 40 DEG C are dried 6h, obtain final product.
Embodiment 2
Proline 0.1g is dissolved in the ethanol of 100mL, is subsequently adding sodium stearyl fumarate 0.1g, obtain adjuvant dispersion
Liquid；Cilostazol 0.1g 20mL ethanol is dissolved, obtains drug susbstance dispersion；Adjuvant dispersion liquid and drug susbstance dispersion are mixed all
Even, 40 DEG C of vacuum reclaim ethanol, lyophilization, obtain final product.
Embodiment 3
Proline 0.1g is dissolved in the ethanol of 200mL, is subsequently adding sodium stearyl fumarate 0.1g, obtain adjuvant dispersion
Liquid；Cilostazol 0.1g 100mL ethanol is dissolved, obtains drug susbstance dispersion；By adjuvant dispersion liquid and drug susbstance dispersion mixing
Uniformly, 30 DEG C of vacuum reclaim ethanol, lyophilization, obtain final product.
Embodiment 4
Proline 0.2g is dissolved in the ethanol of 200mL, is subsequently adding sodium stearyl fumarate 0.2g, obtain adjuvant dispersion
Liquid；Cilostazol 0.1g 50mL ethanol is dissolved, obtains drug susbstance dispersion；Adjuvant dispersion liquid and drug susbstance dispersion are mixed all
Even, 40 DEG C of vacuum reclaim ethanol, and 40 DEG C are dried 6h, obtain final product.
Embodiment 5
Proline 0.1g is dissolved in the ethanol of 100mL, is subsequently adding sodium stearyl fumarate 0.2g, obtain adjuvant dispersion
Liquid；Cilostazol 0.1g 50mL ethanol is dissolved, obtains drug susbstance dispersion；Adjuvant dispersion liquid and drug susbstance dispersion are mixed all
Even, 40 DEG C of vacuum reclaim ethanol, and 40 DEG C are dried 6h, obtain final product.
Embodiment 6
Cilostazol 0.1g and the proline 0.1g ethanol of 200mL are dissolved, are subsequently adding sodium stearyl fumarate 0.1g,
Mix homogeneously, 40 DEG C of vacuum reclaim ethanol, and 40 DEG C are dried 6h, obtain final product.
Embodiment 7
Cilostazol 0.1g, proline 0.1g, sodium stearyl fumarate 0.1g are disperseed with the ethanol of 200mL, mix homogeneously,
40 DEG C of vacuum reclaim ethanol, and 40 DEG C are dried 6h, obtain final product.
Embodiment 8
Cilostazol 0.1g and sodium stearyl fumarate 0.1g are disperseed with the ethanol of 100mL, mix homogeneously, 40 DEG C of vacuum are returned
Receive ethanol, 40 DEG C are dried 6h, obtain final product.
Embodiment 9
Cilostazol 0.1g and proline 0.1g are disperseed with the ethanol of 200mL, mix homogeneously, 40 DEG C of vacuum reclaim second
Alcohol, 40 DEG C are dried 6h, obtain final product.
Embodiment 10
By Cilostazol 0.1g, sodium stearyl fumarate 0.1g and proline 0.1g mix homogeneously, pulverize, sieve and obtain final product.
Embodiment 11
By Cilostazol 0.1g and sodium stearyl fumarate 0.1g mix homogeneously, pulverize, sieve and obtain final product.
Embodiment 12
By Cilostazol 0.1g and proline mix homogeneously, pulverize, sieve and obtain final product.
Embodiment 13
The oral administration biaavailability research of Cilostazol compositionss
Laboratory animal：Male SD rat 112, body weight 200 300g.
Dosage regimen：Experimental mouse is randomly divided into 14 groups, and after fasting 12 hours, the 1st group of gavage gives Cilostazol combination
Thing 1 (preparing by embodiment 1), the 2nd group of gavage gives Cilostazol compositionss 2 (preparing by embodiment 2), and the 3rd group of gavage gives
Cilostazol compositionss 3 (preparing by embodiment 3), the 4th group of gavage gives Cilostazol compositionss 4 (preparing by embodiment 4), the
5 groups of gavages give Cilostazol compositionss 5 (preparing by embodiment 5), and the 6th group of gavage gives Cilostazol compositionss 6 (by enforcement
Prepared by example 6), the 7th group of gavage gives Cilostazol compositionss 7 (preparing by embodiment 7), and the 8th group of gavage gives Cilostazol group
Compound 8 (preparing by embodiment 7), the 9th group of gavage gives Cilostazol compositionss 7 (preparing by embodiment 9), and the 10th group of gavage is given
Give Cilostazol compositionss 10 (preparing by embodiment 10), the 11st group of gavage gives Cilostazol compositionss 11 (by embodiment 11
Preparation), the 12nd group of gavage gives Cilostazol compositionss 12 (preparing by embodiment 12), and it is former that the 13rd group of gavage gives Cilostazol
Material medicine.
Above-mentioned by 30mg/kg, be administered.
Sample collecting：In administration after 0,0.5,1,2,3,4,5,6,7,8,10,12,24h blood is taken by eye socket, process, measure
Cilostazol content.
Result：The 3P97 program matching of mean blood plasma concentration data, Cilostazol each composition oral AUC data respectively with
Cilostazol crude drug is administered orally AUC data and compares, and calculates Cilostazol relative bioavailability, and data is shown in Table 1.
Bioavailability after the administration of table 1 Cilostazol composition oral
| Sample | Bioavailability (%) |
| 1st group | 262.5 |
| 2nd group | 305.2 |
| 3rd group | 283.3 |
| 4th group | 162.6 |
| 5th group | 153.8 |
| 6th group | 140.9 |
| 7th group | 138.5 |
| 8th group | 132.2 |
| 9th group | 127.3 |
| 10th group | 120.5 |
| 11st group | 116.4 |
| 12nd group | 108.1 |
| 13rd group | - |
Summarize：Embodiment 1-3 is that simply drying meanss are different with drying time, and bioavailability is slightly by present invention preparation
There is difference, have very big market promotional value.Embodiment 4-12 is using different from the composition of the present invention, ratio or order of addition,
Result shows the bioavailability that biology degree is far away from the present invention.
Claims (3)
1. a kind of Cilostazol compositionss are it is characterised in that described compositionss are by Cilostazol, sodium stearyl fumarate and dried meat ammonia
Acid is constituted；In described compositionss, the mass ratio of Cilostazol, sodium stearyl fumarate and proline is 1:1:1；Described combination
Thing is realized by following steps：Proline ethanol is dissolved, is subsequently adding sodium stearyl fumarate, obtains adjuvant dispersion liquid；By west
His azoles of Lip river ethanol dissolves, and obtains drug susbstance dispersion；By adjuvant dispersion liquid and drug susbstance dispersion mix homogeneously, reclaim ethanol, do
Dry, obtain final product.
2. a kind of method preparing described Cilostazol compositionss as claimed in claim 1 it is characterised in that
Proline 0.1 g is dissolved in the ethanol of 100mL, is subsequently adding sodium stearyl fumarate 0.1 g, obtains adjuvant dispersion liquid；
Cilostazol 0.1 g 50mL ethanol is dissolved, obtains drug susbstance dispersion；Adjuvant dispersion liquid and drug susbstance dispersion are mixed all
Even, 40 DEG C of vacuum reclaim ethanol, and 40 DEG C are dried 6h, obtain final product.
3. a kind of method preparing described Cilostazol compositionss as claimed in claim 1 it is characterised in that
Proline 0.1 g is dissolved in the ethanol of 100mL, is subsequently adding sodium stearyl fumarate 0.1 g, obtains adjuvant dispersion liquid；
Cilostazol 0.1 g 20mL ethanol is dissolved, obtains drug susbstance dispersion；Adjuvant dispersion liquid and drug susbstance dispersion are mixed all
Even, 40 DEG C of vacuum reclaim ethanol, lyophilization, obtain final product.
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| CN201410505685.5A CN104258403B (en) | 2014-09-28 | 2014-09-28 | A kind of Cilostazol compositionss and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101636152A (en) * | 2007-02-15 | 2010-01-27 | 株式会社Amorepacific | Contain controlled release preparation of cilostazol and preparation method thereof |
| CN101868240A (en) * | 2007-09-21 | 2010-10-20 | 阿斯利康(瑞典)有限公司 | Soluble dosage forms containing cephem derivatives suitable for parenteral administration |
| CN101984968A (en) * | 2010-10-29 | 2011-03-16 | 北京润德康医药技术有限公司 | Preparation method of pharmaceutical preparation of antitumor agent temozolomide |
-
2014
- 2014-09-28 CN CN201410505685.5A patent/CN104258403B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101636152A (en) * | 2007-02-15 | 2010-01-27 | 株式会社Amorepacific | Contain controlled release preparation of cilostazol and preparation method thereof |
| CN101868240A (en) * | 2007-09-21 | 2010-10-20 | 阿斯利康(瑞典)有限公司 | Soluble dosage forms containing cephem derivatives suitable for parenteral administration |
| CN101984968A (en) * | 2010-10-29 | 2011-03-16 | 北京润德康医药技术有限公司 | Preparation method of pharmaceutical preparation of antitumor agent temozolomide |
Non-Patent Citations (1)
| Title |
|---|
| 廖小平 等.西洛他唑临床应用近况.《中国临床药理学杂志》.2012,第28卷(第9期),711-713页. * |
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Effective date of registration: 20170124 Address after: 276111 Shandong city of Linyi province Tancheng County Lizhuang town country road No. 5. Second Tancheng County People''s Hospital Applicant after: Liu Zongxia Address before: 215000 Jiangsu City, Suzhou hi tech Zone Jinfeng Road, building 8, No. 15 Applicant before: Suzhou Pu Luo Da Biotechnology Co., Ltd. |
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