CN1255394C - Process for the manufacture of pacilitaxel nano granule - Google Patents
Process for the manufacture of pacilitaxel nano granule Download PDFInfo
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- CN1255394C CN1255394C CN 02133333 CN02133333A CN1255394C CN 1255394 C CN1255394 C CN 1255394C CN 02133333 CN02133333 CN 02133333 CN 02133333 A CN02133333 A CN 02133333A CN 1255394 C CN1255394 C CN 1255394C
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- taxol
- nano
- paclitaxel
- pure water
- nanometer
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Abstract
The present invention relates to a method for preparing taxol nanometer granules. 0.05 to 5 % of surface active agents are added in an alcohol solution of taxol. Under the condition of stirring in high speed and ultrasonic vibration, a mother solution is dropped to 5 to 500 times of pure water, and a nanometer taxol suspension is obtained after the mother solution is stored in the pure water for definite time. Taxol nanometer granules can be obtained by a method, such as freeze drying, etc. The method of the present invention has the advantages of reliability, easy operation and low energy consumption, and can not pollute environment. The prepared nanometer taxol has high bioactivity, and can exert the therapeutic effect of tacol.
Description
Technical field
The invention belongs to pharmacy field, specifically is the method for the taxol of pure dissolubility being made the nanoparticle of taxol.
Background technology
Taxol (Paclitaxel) is the di-terpene composition of extraction separation from Ramulus et folium taxi cuspidatae or mountain mahogany.Taxol be in July, 1994 by a kind of novel anti microtubule medicine that drugs approved by FDA comes into the market, be a kind of broad-spectrum anti-cancer drug.Now as a line medicine of ovarian cancer and mammary cancer, also effective to existing drug-fast intractable ovarian cancers such as platinum classes, taxol is the tumor chemotherapeutic drug of new generation with important breakthrough.But taxol also has significant toxic side effect, is mainly bone marrow depression and neurotoxicity, the appearance in 2～3 days after medication often of arthrodynia, myalgia, and GPT raises and accounts for 33%, and alopecia sees all patients, often betides to control back the 12nd～21 day.In addition, because taxol content in bark of Ramulus et folium taxi cuspidatae only is 2/10000ths to five, content only is about 5/100000ths in leaf, stem, the extraction process complexity, not only cause taxol to cost an arm and a leg, and the plant resourceses such as Ramulus et folium taxi cuspidatae that considerable damage is now few.For this reason, the pacilitaxel nano granule that development has higher bioavailability significantly reduces its toxic side effect, reduces the taxol using dosage, not only has great economy value and can also reduce medical expense, to preserving the ecological environment major contribution is arranged also.
The objective of the invention is to prepare taxol nanoparticle, improve the bioavailability of taxol, significantly reduce its toxic side effect, reduce the using dosage of taxol,, make full use of plant resourceses such as Ramulus et folium taxi cuspidatae to reach the reduction medical expense.
Summary of the invention
The objective of the invention is to realize by following technical proposals:
1. the alcoholic solution of taxol preparation
Can be made into concentration as required and be the ethanolic soln of 1～10% taxol.Tensio-active agent is added in the alcoholic solution of taxol, make the dropping mother liquor.Surfactant concentrations is 0.05～5%.Ethanol is selected dehydrated alcohol for use, and tensio-active agent is selected tween-80 for use.
2. under stirring and ultrasonic vibration condition, the alcoholic solution that will contain the taxol of tensio-active agent slowly is added drop-wise in the pure water, deposits through certain hour and promptly forms nano-paclitaxel suspension.The consumption of pure water can be 5～500 times of mother liquor.
3. adopt the solvent alcohol in reduction vaporization method removal taxol-aqeous suspension.
4. in order further to improve the bioavailability of pacilitaxel nano granule and to overcome certain biological barrier, can carry out finishing to the nano particle of taxol.
5. obtain the nano-paclitaxel powder as needing, can adopt methods such as vacuum-drying or lyophilize.
Adopt the prepared nano-paclitaxel suspension of the inventive method to measure through laser particle analyzer, its median size is 202 nanometers, through Tongji Medical Univ's killing in vitro cancer cells test, the result shows that under the condition of lower concentration nano-paclitaxel suspension still presents the cancer cells effect of killing significantly (attached test result).
Attached: test result
Taxol and nano-paclitaxel are to the killing experiments of three kinds of tumour cells
One, employing method: lactic dehydrogenase enzyme process
Be in logarithmic growth cell K562, A549, HL-60 furnishing 5 * 10 respectively with three kinds
4/ ml is inoculated in 96 well culture plates, and every hole 100ul adds different concns taxol or nano-paclitaxel respectively, every kind of parallel 3 holes of concentration, and set up blank.Give 10% bovine serum RPMI-1640, every hole adds 100ul, and maximum release aperture adds 100ul 1%NP
40, cultivate after 48 hours.Draw the supernatant part, every hole 100ul adds the substrate of serum lactic dehydrogenase, every hole 100ul, and room temperature was placed after 20 minutes, added 1M citric acid (30ul/ hole) termination reaction.
Two, calculation formula: killing activity=OD (test holes-natural hole)/OD (maximum release aperture-natural hole) * 100%
Three, the results are shown in Table 1, table 2, table 3
Table 1 different concns taxol is to the effect (killing and wounding %) of K562 cell
| Taxol concentration (ug/ml) | 0# | 1# | 2# |
| 100 | 10.7 | 43.8 | 78.3 |
| 50 | 8.3 | 19.2 | 42.2 |
| 20 | 6.3 | 13.5 | 22.8 |
| 10 | 4.2 | 10.3 | 22.5 |
| 5 | 4 | 7.8 | 17.7 |
| 2.5 | 2.2 | 6.3 | 15 |
| 1.25 | 1.8 | 6.3 | 14.8 |
| 0.625 | / | / | 13.8 |
Table 2 different concns taxol is to the lethal effect (killing and wounding %) of A549 cell
| Taxol concentration (ug/ml) | 0# | 1# | 2# |
| 100 | 12.2 | 45.7 | 78 |
| 50 | 10 | 28.4 | 57 |
| 20 | 9.5 | 16.7 | 28 |
| 10 | 7.6 | 10.7 | 22.2 |
| 5 | 5.7 | 9.7 | 20.5 |
| 2.5 | 1.5 | 7.8 | 18.3 |
| 1.25 | 0 | 7.2 | 17.4 |
| 0.625 | / | / | 15 |
Table 3 different concns taxol is to the lethal effect (killing and wounding %) of HL-60 cell
| Taxol concentration (ug/ml) | 0# | 1# | 2# |
| 100 | 11.3 | 40.6 | 80.6 |
| 50 | 9.8 | 22.8 | 51.7 |
| 20 | 8.4 | 16.8 | 29.8 |
| 10 | 5.7 | 12.7 | 25.3 |
| 5 | 3.3 | 11.3 | 23 |
| 2.5 | 3.3 | 11 | 19.3 |
| 1.25 | 3.1 | 10.5 | 17.7 |
| 0.625 | / | / | 17.7 |
Illustrate: 0# is the taxol aqueous solution; 1# is nano-paclitaxel suspension (granularity 316nm);
2# is nano-paclitaxel suspension (granularity 202nm)
The preparation of lactic dehydrogenase enzyme substrates: nitro tetrazolium chloride (NBT) 3.2mg adds oxidized form of nicotinamide-adenine dinucleotide (NAD
+) 8mg, azophenlyene dimethyl ester vitriol (PMS) 0.8mg, add distilled water again to 1.6ml, add Sodium.alpha.-hydroxypropionate 0.4ml, add 0.1M PH7.4PBS to 10ml.
Claims (2)
1. the preparation method of pacilitaxel nano granule is characterized in that taxol is dissolved in the dehydrated alcohol, forms concentration and be the ethanolic soln of 1～10% taxol; Tween-80 is added in the ethanolic soln of taxol, make the dropping mother liquor, surfactant content is 0.05～5%; Under stirring and ULTRASONIC COMPLEX condition, mother liquor is added drop-wise in the pure water then, the consumption of pure water is 5-500 a times of mother liquor, promptly obtains nano-paclitaxel suspension after certain hour is deposited.
2. the preparation method of nano-paclitaxel particulate according to claim 1 is characterized in that further vacuum-drying of resulting nano-paclitaxel suspension or lyophilize are obtained the paclitaxel nano powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02133333 CN1255394C (en) | 2002-06-24 | 2002-06-24 | Process for the manufacture of pacilitaxel nano granule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02133333 CN1255394C (en) | 2002-06-24 | 2002-06-24 | Process for the manufacture of pacilitaxel nano granule |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1463969A CN1463969A (en) | 2003-12-31 |
| CN1255394C true CN1255394C (en) | 2006-05-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02133333 Expired - Fee Related CN1255394C (en) | 2002-06-24 | 2002-06-24 | Process for the manufacture of pacilitaxel nano granule |
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Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829061A (en) * | 2010-05-14 | 2010-09-15 | 无锡纳生生物科技有限公司 | Taxol nanoparticle composition and preparation method thereof |
| CN101973967B (en) * | 2010-10-12 | 2012-09-05 | 东北林业大学 | Method for preparing negative pressure anti-solvent of water-soluble nano-taxol powder |
| KR102551708B1 (en) | 2015-06-04 | 2023-07-06 | 크리티테크, 인크. | Collection device and method of use |
| CN105055341A (en) * | 2015-08-13 | 2015-11-18 | 黑龙江泰华源生物技术有限责任公司 | Paclitaxel and albumin combined freeze-drying preparation and preparation method thereof |
| KR20230017354A (en) | 2016-04-04 | 2023-02-03 | 크리티테크, 인크. | Methods for Solid Tumor Treatment |
| CN106974896A (en) * | 2016-05-10 | 2017-07-25 | 北京德立福瑞医药科技有限公司 | A kind of antitumor agent containing hydrophobicity chemotherapeutics nano particle and Fibrin Glue |
| JP2020523285A (en) | 2017-06-09 | 2020-08-06 | クリチテック，インコーポレイテッド | Treatment of epithelial cysts by intracystic injection of antitumor particles |
| US10398646B2 (en) | 2017-06-14 | 2019-09-03 | Crititech, Inc. | Methods for treating lung disorders |
| CN111278436A (en) | 2017-10-03 | 2020-06-12 | 克里蒂泰克公司 | Local delivery of anti-tumor particles in combination with systemic delivery of immunotherapeutic agents for the treatment of cancer |
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2002
- 2002-06-24 CN CN 02133333 patent/CN1255394C/en not_active Expired - Fee Related
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| CN1463969A (en) | 2003-12-31 |
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