Paclitaxel slow-release temperature-sensitive gel and preparation method thereof

A temperature-sensitive gel and temperature-sensitive gel matrix technology, which can be used in pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., can solve the problems of fast drug release rate, low solubility, insufficient strength, etc. Reduce systemic side effects, improve therapeutic efficacy, and facilitate administration

Active Publication Date: 2016-07-27
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, due to the low solubility of paclitaxel in water, most thermosensitive gels have small molecular weight, insufficient strength, poor stability in vivo, and easy depolymerization, resulting in too fast drug release rate in vivo (McKenzieM, BettsD, SuhA, BuiK, KimLD, ChoH.Hydrogel-baseddrugdeliverysystemsforpoorlywater-solublerugs. Molecules.2015, 20(11):20397-408)
So far there is no research report on Soluplus as a thermosensitive gel

Method used

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  • Paclitaxel slow-release temperature-sensitive gel and preparation method thereof
  • Paclitaxel slow-release temperature-sensitive gel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Preparation of paclitaxel-Soluplus, paclitaxel-poloxamer 407 thermosensitive gel

[0044] Isotonic phosphate buffer solution is prepared as follows: Weigh NaCl8g, KH 2 PO 4 0.2g, Na 2 HPO 4 12H 2 Add O2.9g and KCl0.2g into the container, then add 1000mL of degassed water for injection to dissolve, and adjust the pH to 7.4 with NaOH.

[0045] Add Soluplus to isotonic phosphate buffer, swell at 4°C to obtain a uniform dispersion system, and pass through 0.45 μm and 0.22 μm microporous membranes to sterilize the obtained dispersion at 0-30°C, as a temperature-sensitive gel matrix system; dissolving paclitaxel in ethanol to prepare a paclitaxel solution; then adding the paclitaxel solution to the Soluplus thermosensitive gel matrix system under stirring at room temperature to obtain a paclitaxel-Soluplus or paclitaxel-poloxamer 407 thermosensitive gel (0-30°C Store for future use, in a uniformly dispersed dispersion system).

[0046] Add Poloxamer 407 into i...

Embodiment 2

[0050] Example 2 Determination of In Vitro Release of Paclitaxel-Soluplus and Paclitaxel-Poloxamer 407 Thermosensitive Gel

[0051] Take the temperature-sensitive gel preparation prepared in Example 1, and adopt the filmless release rate measurement method. Accurately weigh 0.2mL paclitaxel thermosensitive gel respectively, put them in test tubes, let stand at 37°C for 5min, and wait for them to gel completely; Shake (37°C, 100rpm), sample 1mL at different time points, and add 1mL of fresh medium at the same temperature. The sample was centrifuged at 10,000 rpm for 5 min, and the supernatant was taken, and the concentration of paclitaxel was determined by HPLC. Comparison of in vitro release of paclitaxel-Soluplus and paclitaxel-poloxamer 407 thermosensitive gel figure 1 .

[0052] Conclusion: When 20% poloxamer 407 was used as the thermosensitive gel matrix, the cumulative release of paclitaxel reached 60% in 6 hours in vitro, and nearly 90% in 48 hours. When Soluplus is ...

Embodiment 3

[0053] Example 3 Comparison of In Vivo Formability, Retention and Release of Paclitaxel-Soluplus and Paclitaxel-Poloxamer 407 Thermosensitive Gels

[0054] In Example 1, paclitaxel-Soluplus (10%, 20%) or paclitaxel-poloxamer 407 (20%) thermosensitive gel was injected into 0.2 mL of mice (ICR, male, body weight 30 ± 5g, Zhejiang Academy of Medical Sciences) subcutaneously on the back, 3 mice in each group, the mice were sacrificed regularly, the subcutaneous section was cut open and the gelation situation of the preparation in vivo was observed, and the drug content in the residual gel was determined by HPLC. Comparison of In Vivo Formability of Paclitaxel-Soluplus and Paclitaxel-Poloxamer 407 Thermosensitive Gels figure 2 .

[0055] Conclusion: 6 hours after subcutaneous injection of 20% F127 drug-loaded gel, there is only a very small amount of gel residue in the injection site. The residual drug concentration measured by HPLC method is only 25.7±2.3% of the injected amount...

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Abstract

The invention provides paclitaxel slow-release temperature-sensitive gel and a preparation method thereof. The paclitaxel slow-release temperature-sensitive gel is prepared from, by weight, 0.01%-5% of paclitaxel, 0.5%-27% of organic solvent and the balance Soluplus-based temperature-sensitive gel matrix. The phase transition temperature of the paclitaxel slow-release temperature-sensitive gel system is more approximate to the body temperature compared with the gelatinization temperature of poloxamer 407 temperature-sensitive gel, administration is convenient, the strength of the gel formed in the body is higher than that of the poloxamer 407 temperature-sensitive gel, and drug slow release can last for at least seven days after a hypodermic injection while drug slow release of poloxamer 407 can only last for about one day. The paclitaxel slow-release temperature-sensitive gel is administrated through a by-tumor local injection or at a solid tumor removing position, the treatment effect of a cancer can be improved, the toxic and side effect on the whole body can be lowered, and the treatment effect is remarkable and better than that of paclitaxel-poloxamer 407 temperature-sensitive gel.

Description

(1) Technical field [0001] The invention relates to a novel paclitaxel sustained-release temperature-sensitive gel and a preparation method thereof. (2) Background technology [0002] Paclitaxel is a commonly used broad-spectrum anticancer drug, mainly used in the treatment of ovarian cancer, breast cancer, small cell lung cancer, prostate cancer, and lymphoma. The solubility of paclitaxel in water is extremely low, about 0.3 μg / mL; and there are serious toxic and side effects, which limit its clinical dosage and medication cycle. Currently commercially available preparations mainly include injection (Taxol), liposome (Lipusu), nanosuspension (albumin-bound) ) and polymer micelles All administered intravenously. [0003] Thermosensitive gel refers to a new type of drug-loading system that is in a flowing liquid state at room temperature and rapidly phase-transforms to form a gel at body temperature. It is used for local injection and can prolong the residence time of th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/34A61K31/337A61P35/00
CPCA61K9/0002A61K9/0012A61K9/0019A61K9/06A61K31/337A61K47/34
Inventor 熊素彬陈芳吴慧敏尹小东
Owner ZHEJIANG UNIV OF TECH
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