Epothilone B polymer nanoparticle preparation for treating tumors and preparation method thereof

A technology of epothilones and polymers, which is applied in the field of epothilone B polymer nanoparticle preparations and its preparation, can solve the problems of being unsuitable for large-scale production, inability to perform filtration sterilization, poor process repeatability, etc., and achieve Prolong the action time in vivo, improve the anti-tumor effect, avoid the effect of esterase hydrolysis and RES phagocytosis

Inactive Publication Date: 2016-09-28
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although polymer nanoparticle preparations have unique advantages in antitumor drug delivery, their preparation method is still one of the main factors limiting their large-scale production
Patents CN1017732234A and CN101972480A use the film dispersion method to obtain micellar solutions, and the process repeatability is poor; patent CN103585634A uses the microfluidic method to inject the organic solvent solution of drugs and polymer materials into the water phase at a flow rate of 0.2mL / min, which takes a long time to prepare , not suitable for large-scale production; and the polymer nanoparticles prepared by CN102247325A have a relatively large particle size, within the range of 50-450nm, and cannot be sterilized by filtration

Method used

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  • Epothilone B polymer nanoparticle preparation for treating tumors and preparation method thereof
  • Epothilone B polymer nanoparticle preparation for treating tumors and preparation method thereof
  • Epothilone B polymer nanoparticle preparation for treating tumors and preparation method thereof

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Effect test

Embodiment 1

[0032] Dissolve 0.2g epothilone B and 1.8g PEG-PLA in 10mL dichloromethane as the organic phase, and dissolve 0.2g poloxamer 188 in 100mL double-distilled water as the water phase. The organic phase was added to the water phase, stirred for 3 minutes at 8°C, and circulated 6 times with a high-pressure homogenizer at a pressure of 6000 psi; the obtained emulsion was placed in a tangential flow filtration system with a membrane molecular weight cut-off of 100kDa, and removed at 40°C. The epothilone B polymer nanoparticle preparation for treating tumors is obtained after the organic solvent and the free drug are concentrated, filtered and sterilized, and freeze-dried. Its average particle size is 110.2nm, and the epothilone B drug loading is 2.3%.

Embodiment 2

[0034] Dissolve 0.2g epothilone B and 1.8g PEG-PLA in 10mL dichloromethane as the organic phase, and dissolve 0.2g poloxamer 188 in 100mL double-distilled water as the water phase. The organic phase was added to the water phase, stirred for 3 minutes at 8°C, and circulated 6 times with a high-pressure homogenizer at a pressure of 6,000 psi; the obtained emulsion was placed in a tangential flow filtration system with a membrane molecular weight cut-off of 100kDa, and removed at 20°C. The epothilone B polymer nanoparticle preparation for treating tumors is obtained after the organic solvent and the free drug are concentrated, filtered and sterilized, and freeze-dried. Its particle size distribution figure 1 As shown, the average particle diameter is 100.2nm, and the epothilone B drug loading is 7.8%.

Embodiment 3

[0036] Dissolve 0.2g epothilone B, 1.0g PEG-PLA and 0.8g PLA together in 10mL dichloromethane as the organic phase, 0.2g poloxamer 188 is dissolved in 100mL double distilled water as the water phase, stir at 6000rpm The organic phase was added to the water phase at a high speed, stirred for 3 min at 8°C, and circulated 6 times using a high-pressure homogenizer at a pressure of 6000 psi; the resulting emulsion was placed in a tangential flow filtration system, and the molecular weight cut-off of the membrane was 100 kDa , after removing the organic solvent and free drug at 10° C., concentrating, sterilizing by filtration, and freeze-drying, the epothilone B polymer nanoparticle preparation for treating tumors was obtained. The average particle size was 132.5 nm, and the drug loading of epothilone B was 8.9%.

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Abstract

The invention discloses an epothilone B polymer nanoparticle preparation for treating tumors and a preparation method thereof. The polymer nanoparticle preparation is composed of epothilone B, a polymer carrier material and a lyoprotectant; the nanoparticle preparation has a particle size of 10-200 nm. The preparation method of the nanoparticle preparation comprises the following steps: mixing an organic solvent solution of the polymer carrier material and epothilone B with an aqueous phase containing an emulsifier according to a ratio, homogenizing, removing an organic solvent, concentrating, filtering and disinfecting, and lyophilizing to obtain the preparation. By changing the prescription process parameters of the polymer carrier material such as composition, concentration and organic solvent removal temperature, drug loading capacity, drug release speed and other features are adjusted; the preparation prepared herein has good slow release effect and can effectively prevent epothilone B from being hydrolyzed and deactivated by esterase in body, significantly prolonging in-vivo circulation time, improving antitumor activity and lowering medicine toxicity.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations and provides an epothilone B polymer nanoparticle preparation for treating tumors and a preparation method thereof. Background technique [0002] Epothilone B is a macrolide antineoplastic drug. Its antitumor mechanism is similar to taxane. tumor effect. It is superior to paclitaxel with the same mechanism of action in terms of anti-multidrug resistance, anti-tumor spectrum, anti-tumor activity, and safety. Studies have shown that the antitumor activity of epothilone B in vitro is 50-500 times higher than that of paclitaxel. A number of phase II clinical studies of epothilone B in the treatment of ovarian cancer, peritoneal cancer, prostate cancer and breast cancer have achieved good results. However, the lactone ring of epothilone B (structure as in formula I) is easily hydrolyzed and inactivated by esterase in the body, which greatly reduces its anti-tumor effect in vivo, which is a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K31/427A61K47/34A61P35/00
CPCA61K9/5146A61K9/0002A61K9/0019A61K31/427
Inventor 林霞杨子毅
Owner JIANGNAN UNIV
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