CN101129338A - Minuteness anti-cancer medicine paclitaxel of novel technique supercritical fluid - Google Patents
Minuteness anti-cancer medicine paclitaxel of novel technique supercritical fluid Download PDFInfo
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- CN101129338A CN101129338A CNA2007100498445A CN200710049844A CN101129338A CN 101129338 A CN101129338 A CN 101129338A CN A2007100498445 A CNA2007100498445 A CN A2007100498445A CN 200710049844 A CN200710049844 A CN 200710049844A CN 101129338 A CN101129338 A CN 101129338A
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Abstract
The paclitaxel has broad spectrum antineoplastic activity, which is used to treat oophoron cancer and breast cancer, has the significant effect, and is known as a anti-cancer drug with the wide developing prospect, but the particle diameter of paclitaxel medicine powder is bigger so that the paclitaxel medicine powder isn't absorbed by administer orally, has the lower bioavailability, and limits the clinic application of paclitaxel. The invention makes Paclitaxel fine with supercritical flow new technique. The experiment makes Paclitaxel fine with above-critical CO2 as the dissolvent and with supercritical flow forced disperse solution technique, which researches the influence of the pressure, the temperature, the concentration of the solution and the flow speed of the solution for the shape, grain diameter and the distribution of fine paclitaxel. The result indicates that the nanometer grain diameter can be changed in the finite range by changing the technology parameter, wherein the prepared surface of the nanometer grain is smooth, and has the good sphericity, and the average grain diameter is 670nm-940nm, the concentration of the solution and the flow speed is the main factor.
Description
Technical field
The invention belongs to novel preparation method and applied technical field that medicine physical features and pharmaceutical dosage form change, particularly relate to and adopt new method new technique miniaturization medicine.
Background technology
Paclitaxel has broad-spectrum anti-tumor activity, can be used for treating ovarian cancer, breast carcinoma, nonsmall-cell lung cancer, pernicious black solid tumor and some other solid tumors, evident in efficacy to treatment transitivity ovarian cancer, breast carcinoma especially, be acknowledged as very rising PTS.Existing at present more than 50 national approveds are sold taxol biosynthesis.According to American National ICR (NCI) prediction, paclitaxel will become one of anticancer choice drug in 10-15 from now on.
Because the taxol drug powder diameter is bigger, oral absorption hardly, bioavailability is low, has greatly limited clinical application of taxol.Can accelerate absorbed speed greatly behind the medicine super-refinement, improve curative effect, reduce dosage.By the particle diameter and the particle size distribution of control drug microparticles, can control drug release speed, thus control medicine concentration in vivo.The method that is often used as the miniaturization medicine has spray drying method, emulsifying volatility process, grinding etc.Yet these methods are not that temperature is too high, have a large amount of organic solvent residuals exactly, and are difficult to control diameter of aspirin particle size and little particle size distribution.In recent years, the supercritical fluid anti-solvent technology has been successfully applied to the preparation polymer beads, this technology is subjected to the researcher common concern in the polymer support Application for Field, its ultimate principle is to utilize supercritical fluid as anti-solvent, organic solvent in the absorbent solution, reduce the solvability of organic solvent, make the solute supersaturation and deposit and separate out the formation granule solute.The supercritical fluid that grows up on the SAS basis is forced dispersion soln technology (Solution-enhanced dispersion by supercritical fluids, SEDS), with coaxial two streaming nozzle application in the SAS process so that solution fully atomize, increase mass transfer effect, thereby obtain higher solution supersaturation speed and crystalline deposit speed to prepare more tiny granule.
This experiment is at the supercritical CO that designs voluntarily
2On the granulation device, adopt supercritical CO
2Anti-solvent method is the miniaturization anti-cancer medicine paclitaxel first, and has investigated the influence to microsphere pattern, size and distribution thereof of technological parameter that material impact is arranged on the early-stage Study basis.
Summary of the invention
The object of the present invention is to provide a kind of method of new miniaturization medicine, solve traditional method and can not prepare the needed diameter of aspirin particle of drug world, shape characteristic, physical characteristic.
The objective of the invention is to be achieved through the following technical solutions:
The step of concrete grammar is as follows:
The continous way anti-dissolving agent process can be described below: the CO in the steel cylinder
2Through refrigeration system liquefaction, by the high-pressure plunger pump pressurization, the water bath with thermostatic control in the pipeline pumps in the autoclave after heating up, and treats to meet the requirements of pressure in the still, keeps CO
2Pump into speed, open vent valve and exit, to keep the still internal pressure constant with given pace; After reaching experimental temperature, drug solution pumps into autoclave by high performance liquid chromatography (HPLC) pump through still top nozzle, regulates outside drying baker of autoclave and pipeline bath temperature, and the control temperature in the kettle is regulated vent valve, keeps the still internal pressure.After finishing the pump sample, keep pressure and temperature-resistant, continue to use CO
2Behind the dry certain hour, slowly release when treating that the still internal pressure is reduced to normal pressure, is taken out sample.
Purposes of the present invention: the present invention is mainly used in the miniaturization cancer therapy drug, improves the dissolubility of medicine, improves the bioavailability of paclitaxel, improves the curative effect of Drug therapy cancer.
The product purity height that method of the present invention is prepared, good dispersion, environmentally safe, and greatly reduce organic residual quantity that other traditional method drug prepared microgranules exist.
The paclitaxel nano grain that adopts method of the present invention to obtain, as shown in Figure 2.
The method of miniaturization medicine of the present invention is simple, is easy to apply.
Description of drawings
Fig. 1. primary taxol drug granule;
The ultra-fine taxol drug granule of Fig. 2 .SEDS method preparation;
The ultra-fine paclitaxel diameter of particle size and the distribution of the preparation of Fig. 3 .SEDS method.
The specific embodiment
(1). anti-cancer medicine paclitaxel organic solution
In reaction bulb, add the 200-300mg paclitaxel, add quantitative organic solvent, under room temperature, dissolve.
(2). the modulation of system process parameter
After reaching the temperature and pressure of requirement of experiment, supercritical CO
2By the coaxial two streaming nozzle outer passage in autoclave top, organic solution by the nozzle inner channel, pumps into autoclave, supercritical CO by high performance liquid chromatography (HPLC) pump simultaneously by high-pressure plunger pump
2As disperse medium organic solution is forced to disperse,, absorb the organic solvent in the solvent soln simultaneously also as anti-solvent.
(1). polymer organic solution
In reaction bulb, add the 200-300mg polymer, change the organic solvent amount, adjust taxol drug concentration, under room temperature, dissolve.
(2). the modulation of system process parameter
After changing the temperature and pressure of requirement of experiment, supercritical CO
2By the coaxial two streaming nozzle outer passage in autoclave top, organic solution by the nozzle inner channel, pumps into autoclave, supercritical CO by high performance liquid chromatography (HPLC) pump simultaneously by high-pressure plunger pump
2As disperse medium organic solution is forced to disperse,, absorb the organic solvent in the solvent soln simultaneously also as anti-solvent.
Claims (4)
1. a new method that is used for the miniaturization medicine is characterized in that, at the supercritical CO that designs voluntarily
2On the device, adopt supercritical CO
2Anti-solvent method miniaturization anti-cancer medicine paclitaxel, and investigated the influence of solution concentration, solution flow rate to taxol drug nanometer appearance, size and the distribution thereof of miniaturization.
2. according to the new method of right 1 described miniaturization paclitaxel, it is characterized in that drug concentrations at 0.25%wt/v-0.5%wt/v, the flow velocity of HPLC is at 0.25-0.5ml/min.
3. according to the new method of right 1 described miniaturization paclitaxel, it is characterized in that CO
2Flow velocity at 16-32NL/h, temperature is at 32-40 ℃, pressure is at 10-16MPa.
4. according to the new method of right 1 described miniaturization paclitaxel, it is characterized in that the design of coaxial nozzle.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100498445A CN101129338A (en) | 2007-08-27 | 2007-08-27 | Minuteness anti-cancer medicine paclitaxel of novel technique supercritical fluid |
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| CNA2007100498445A CN101129338A (en) | 2007-08-27 | 2007-08-27 | Minuteness anti-cancer medicine paclitaxel of novel technique supercritical fluid |
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| CN101129338A true CN101129338A (en) | 2008-02-27 |
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| CNA2007100498445A Pending CN101129338A (en) | 2007-08-27 | 2007-08-27 | Minuteness anti-cancer medicine paclitaxel of novel technique supercritical fluid |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20190216767A1 (en) * | 2017-03-15 | 2019-07-18 | Dfb Soria, Llc | Topical therapy for the treatment of skin keratoses using nanoparticles of taxanes |
| US10449162B2 (en) | 2015-09-16 | 2019-10-22 | Dfb Soria Llc | Delivery of drug nanoparticles and methods of use thereof |
| US10555898B2 (en) | 2017-03-15 | 2020-02-11 | Dfb Soria, Llc | Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes |
| US10729673B2 (en) | 2015-06-04 | 2020-08-04 | Crititech, Inc. | Taxane particles and their use |
| US10874660B2 (en) | 2016-04-04 | 2020-12-29 | CritlTech, Inc. | Methods for solid tumor treatment |
| US11058639B2 (en) | 2017-10-03 | 2021-07-13 | Crititech, Inc. | Local delivery of antineoplastic particles in combination with systemic delivery of immunotherapeutic agents for the treatment of cancer |
| US11160754B2 (en) | 2017-06-14 | 2021-11-02 | Crititech, Inc. | Methods for treating lung disorders |
| US11497726B2 (en) | 2018-03-16 | 2022-11-15 | Dfb Soria, Ll. | Topical therapy for the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer using nanoparticles of taxanes |
| US11523983B2 (en) | 2017-06-09 | 2022-12-13 | Crititech, Inc. | Treatment of epithelial cysts by intracystic injection of antineoplastic particles |
-
2007
- 2007-08-27 CN CNA2007100498445A patent/CN101129338A/en active Pending
Cited By (23)
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|---|---|---|---|---|
| US10993927B2 (en) | 2015-06-04 | 2021-05-04 | Crititech, Inc. | Taxane particles and their use |
| US11123322B2 (en) | 2015-06-04 | 2021-09-21 | Crititech, Inc. | Taxane particles and their use |
| EP3838264A1 (en) * | 2015-06-04 | 2021-06-23 | Crititech, Inc. | Taxane particles and their use |
| US10729673B2 (en) | 2015-06-04 | 2020-08-04 | Crititech, Inc. | Taxane particles and their use |
| US11331278B2 (en) | 2015-09-16 | 2022-05-17 | Dfb Soria, Llc | Delivery of drug nanoparticles and methods of use thereof |
| US10449162B2 (en) | 2015-09-16 | 2019-10-22 | Dfb Soria Llc | Delivery of drug nanoparticles and methods of use thereof |
| US10918606B2 (en) | 2015-09-16 | 2021-02-16 | Dfb Soria, Llc | Delivery of drug nanoparticles and methods of use thereof |
| US10894045B2 (en) | 2016-04-04 | 2021-01-19 | Crititech, Inc. | Methods for solid tumor treatment |
| US11458133B2 (en) | 2016-04-04 | 2022-10-04 | Crititech, Inc. | Methods for solid tumor treatment |
| US11033542B2 (en) | 2016-04-04 | 2021-06-15 | Crititech, Inc. | Methods for solid tumor treatment |
| US10874660B2 (en) | 2016-04-04 | 2020-12-29 | CritlTech, Inc. | Methods for solid tumor treatment |
| US11191717B2 (en) | 2017-03-15 | 2021-12-07 | Dfb Soria, Llc | Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes |
| US10555898B2 (en) | 2017-03-15 | 2020-02-11 | Dfb Soria, Llc | Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes |
| US20190216767A1 (en) * | 2017-03-15 | 2019-07-18 | Dfb Soria, Llc | Topical therapy for the treatment of skin keratoses using nanoparticles of taxanes |
| US10842736B2 (en) | 2017-03-15 | 2020-11-24 | Dfb Soria, Llc | Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes |
| US11633349B2 (en) | 2017-03-15 | 2023-04-25 | Dfb Soria, Llc | Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes |
| US11737972B2 (en) | 2017-06-09 | 2023-08-29 | Crititech, Inc. | Treatment of epithelial cysts by intracystic injection of antineoplastic particles |
| US11523983B2 (en) | 2017-06-09 | 2022-12-13 | Crititech, Inc. | Treatment of epithelial cysts by intracystic injection of antineoplastic particles |
| US11160754B2 (en) | 2017-06-14 | 2021-11-02 | Crititech, Inc. | Methods for treating lung disorders |
| US11583499B2 (en) | 2017-10-03 | 2023-02-21 | Crititech, Inc. | Local delivery of antineoplastic particles in combination with systemic delivery of immunotherapeutic agents for the treatment of cancer |
| US11058639B2 (en) | 2017-10-03 | 2021-07-13 | Crititech, Inc. | Local delivery of antineoplastic particles in combination with systemic delivery of immunotherapeutic agents for the treatment of cancer |
| US11918691B2 (en) | 2017-10-03 | 2024-03-05 | Crititech, Inc. | Local delivery of antineoplastic particles in combination with systemic delivery of immunotherapeutic agents for the treatment of cancer |
| US11497726B2 (en) | 2018-03-16 | 2022-11-15 | Dfb Soria, Ll. | Topical therapy for the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer using nanoparticles of taxanes |
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