CN1098026A - Process for preparing nm-class capsules of cyanoacrylate by semi-continuous emulsion polymerizing process - Google Patents
Process for preparing nm-class capsules of cyanoacrylate by semi-continuous emulsion polymerizing process Download PDFInfo
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- CN1098026A CN1098026A CN 93109466 CN93109466A CN1098026A CN 1098026 A CN1098026 A CN 1098026A CN 93109466 CN93109466 CN 93109466 CN 93109466 A CN93109466 A CN 93109466A CN 1098026 A CN1098026 A CN 1098026A
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- milimicron
- vesicle
- insulin
- cyanoacrylate
- milimicron vesicle
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Abstract
The a-cyanoacrylate milimicron vesicle has certain tissue target tropism, characteristics such as biodegradable and the property alleviated, as pharmaceutical carrier wide prospect is arranged, milimicron vesicle preparation at present takes the interface pump legal in fat-soluble medicine encapsulation ratio higher (generally greater than 50%), and adopt emulsion polymerization not high to the water soluble drug encapsulation ratio, the highlyest be no more than 50%.Thereby its application is restricted.The present invention takes improved semi-continuous emulsion polymerizing method, has prepared water-soluble fluidity medicine milimicron vesicles such as cis-platinum, adriamycin, daunorubicin and insulin, and encapsulation ratio all improves a lot, and reaches as high as 89%.Its milimicron vesicle size is even, and animal experiment shows that above-mentioned milimicron vesicle can improve drug effect, reduces toxicity, and the insulin milimicron vesicle can be expected to make insulin oral preparation by intestinal absorption, thereby has higher utility.
Description
The invention belongs to the milimicron vesicle new preparation process
A-cyanoacrylate has characteristics such as nontoxic, biodegradable, has been used for surgical clinical.It is made the milimicron vesicle material have certain tissue target tropism as pharmaceutical carrier, characteristics such as biodegradable and slow release, particularly its milimicron vesicle can not destroyed by gastric juice, and by the characteristics of enteron aisle degraded absorption, be expected good carrier as oral insulin medicament, the nineties has begun clinic trial abroad, and its economic outlook is very considerable.Use the made a-cyanoacrylate milimicron vesicle of interfacial polymerization to fat-soluble medicine encapsulation ratio higher (can surpass 50%) at present, but complicated process of preparation, productive rate is not high and need a large amount of organic solvents, is difficult to large-scale production.Adopt emulsion polymerization to produce milimicron vesicle to water soluble drug, its encapsulation ratio is lower, the highlyest is no more than 50%.Thereby its application is restricted.
The present invention has improved traditional emulsion polymerization, makes the encapsulation ratio of a-cyanoacrylate milimicron vesicle of water soluble drug improve greatly, and especially the encapsulation ratio to insulin reaches 89%.Simple for process, thus make the fairly large production of water soluble drug a-cyanoacrylate milimicron vesicle become possibility.
This milimicron vesicle prescription following (all by weight)
Surfactant 0.1～1%
Water soluble drug 0.02～0.1%
A-cyanoacrylate 0.5～3%
Other additive 0.1～0.5%
Deionized water 92～98%
[example 1] removes ionized water 40～80ml, add 0.1～0.5 gram nonionic surface active agent, at 0～30 ℃, add 2～3 of injections of insulin (every 400 unit) under the high-speed stirred, with watery hydrochloric acid regulator solution pH value is 1～5, add 0.05～0.1 gram α-Qing Jibingxisuanzhengdingzhi, reacted 20～50 minutes, make seed solution, by formula rate residual monomer is dropwise added, reacted filtering and concentrating 1～2 hour, dialyse, can obtain the insulin milimicron vesicle colloidal solution of concentration 0.5～2%.Measure through AAS and isotope-labelling method, encapsulation ratio can reach 89%.Its particle size of electromicroscopic photograph measurement result is even, and diameter is that 100 ± 10nm(sees Fig. 1).Behind oral 24 hours of the SD rat, its whole blood blood sugar obviously descends and (reduces to 2～3mmol/L) from 33.3mmol/L, recover hyperglycaemia after 120～144 hours again.Illustrate that this milimicron vesicle can make the rat blood sugar (see figure 2) that descends significantly, milimicron vesicle is not destroyed by gastric juice, can be by intestinal absorption.Therefore be expected to make insulin oral preparation, the trouble that makes numerous diabetics avoid injecting, thereby have very vast market prospect.
Example 2: deionized water 40～80ml adds nonionic surface active agent 0.1～0.5 gram, adding the 50mg daunorubicin under 0～30 ℃ of high-speed stirred, is 1～5 with watery hydrochloric acid regulator solution pH value, adds 0.05～0.2 gram α-Qing Jibingxisuanzhengxinzhi again, reacted 30 minutes, and made seed solution.By formula rate residual monomer is dropwise added, reacted 30～70 minutes, dialysis.Promptly obtain 0.5～2% daunorubicin milimicron vesicle, through spectrophotometry, the packing rate reaches 68%, shows through zoopery, compares with daunorubicin, and the toxicity of daunorubicin milimicron vesicle obviously reduces, and tumor killing effect increases.Drug treating time improves nearly 20% than original.
Process using semi-continuous emulsion polymerizing method of the present invention, at first prepare seed solution, because the seed microballoon is to the suction-operated of water soluble drug and insulin, make medicine and insulin be enriched on the seed microballoon, add residual monomer polymerization on the seed microballoon again, encapsulation ratio improves greatly, the stability of its latex on the other hand, and uniformity increases.Use this technology and made serial a-cyanoacrylate milimicron vesicles such as cis-platinum, adriamycin, daunorubicin and insulin, compare with the conventional emulsion polymerization, its encapsulation ratio all improves a lot, and has successfully made the cis-platinum milimicron vesicle.Demonstrate distinctive popularity of this technology and huge market potential.
The description of the drawings:
Fig. 1 is insulin milimicron vesicle negative staining electron microscope photo (amplifying 50000 times)
Fig. 2 is the influence (n=4) of oral insulin milimicron vesicle to the diabetes rat fasting blood-glucose, ordinate is blood sugar (mmol/L), abscissa be the time (my god),-o-is insulin milimicron vesicle zoopery result,--*--is free insulin zoopery result,--be buffer solution control-animal experimental result.
Claims (3)
1, a kind of semi-continuous emulsion polymerizing legal system is equipped with a-cyanoacrylate milimicron vesicle new technology, it is characterized in that making earlier a-cyanoacrylate seed millimicro ball, adds residual monomer emulsion polymerisation on the seed microballoon again.
2, according to the described a kind of stability of claim (1) milimicron vesicle colloid preferably, its stability is provided by semi-continuous emulsion polymerizing technology.
3, according to the described a kind of milimicron vesicle higher to encapsulation ratios such as water soluble drug such as daunorubicin, insulin of claim (1), its higher encapsulation ratio is provided by semi-continuous emulsion polymerizing technology.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 93109466 CN1098026A (en) | 1993-07-30 | 1993-07-30 | Process for preparing nm-class capsules of cyanoacrylate by semi-continuous emulsion polymerizing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 93109466 CN1098026A (en) | 1993-07-30 | 1993-07-30 | Process for preparing nm-class capsules of cyanoacrylate by semi-continuous emulsion polymerizing process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1098026A true CN1098026A (en) | 1995-02-01 |
Family
ID=4987629
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 93109466 Pending CN1098026A (en) | 1993-07-30 | 1993-07-30 | Process for preparing nm-class capsules of cyanoacrylate by semi-continuous emulsion polymerizing process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1098026A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100345535C (en) * | 2000-06-27 | 2007-10-31 | 株式会社Mitech | The Controlled release preparation of insulin and its method |
| CN101585892B (en) * | 2008-05-22 | 2010-09-29 | 中国科学院化学研究所 | Method for preparing polymeric microspheres |
| CN102307654A (en) * | 2009-02-09 | 2012-01-04 | 瑞典树木科技公司 | Polymer shells |
-
1993
- 1993-07-30 CN CN 93109466 patent/CN1098026A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100345535C (en) * | 2000-06-27 | 2007-10-31 | 株式会社Mitech | The Controlled release preparation of insulin and its method |
| CN101585892B (en) * | 2008-05-22 | 2010-09-29 | 中国科学院化学研究所 | Method for preparing polymeric microspheres |
| CN102307654A (en) * | 2009-02-09 | 2012-01-04 | 瑞典树木科技公司 | Polymer shells |
| CN102307654B (en) * | 2009-02-09 | 2015-01-21 | 切卢科技公司 | Polymer shells |
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|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |