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Oxaliplatin-containing nano-micelle preparation and medical application thereof

A technology of oxaliplatin and nano micelles, which is applied in the field of pharmaceutical preparations, can solve the problems of significant toxicity, multiple distributions, and lack of specificity, and achieve the effects of improving medicinal effects, simple preparation methods, and prolonging the storage period

Inactive Publication Date: 2021-12-24
AFFILIATED CANCER HOSPITAL OF SHANDONG FIRST MEDICAL UNIV SHANDONG CANCER INST (SHANDONG CANCER HOSPITAL)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Due to the lack of specificity of distribution in vivo, antineoplastic drugs are more distributed in normal tissues, resulting in significant toxic effects

Method used

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  • Oxaliplatin-containing nano-micelle preparation and medical application thereof
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  • Oxaliplatin-containing nano-micelle preparation and medical application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0024] 1. Preparation of oxaliplatin copolymer micelles (taking Pluronic 123 as the hydrophilic segment as an example)

[0025] Dissolve Pluronic 123 (P123), tocopheryl succinate (TOS), and condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide in DMSO, and the mixture is continuously stirred After 10 hours, the produced chemical polymer was dialyzed with a dialysis bag with a molecular weight cut-off of 3500, and the product was freeze-dried and sieved to obtain P123-TOS copolymer micelles.

[0026] Dissolve oxaliplatin and sieved P123-TOS copolymer micelles in acetonitrile and stir for 40 minutes, then put the above organic mixture in a dialysis bag, dialyze in distilled water for 12 hours, replace the distilled water every 3 hours, and the dialysis is completed After centrifugation under a high-speed centrifuge, the supernatant was filtered and freeze-dried through a 0.45 μm microporous membrane to obtain oxaliplatin-P123-TOS copolymer micelles

[0027] Two, specif...

Embodiment 1

[0028] Embodiment 1: the formulation containing oxaliplatin nanomicelle

[0029]

[0030]

[0031] Weigh mannitol, lactose and sodium acetate, add 80% water for injection, dissolve and stir evenly, then add oxaliplatin-P123-TOS copolymer micelles after passing through a 200 mesh sieve, dissolve and stir evenly, and use 0.1 mol / L hydrochloric acid or 0.1mol / L sodium hydroxide solution to adjust the pH to 6.5, after passing the intermediate inspection, add water for injection to make up to full volume. The solution was sent to a sterile room by a peristaltic pump, filtered through a 0.22 μm microporous membrane until clear, and freeze-dried to obtain a freeze-dried powder injection containing oxaliplatin nanomicelles.

Embodiment 2

[0032] Embodiment 2: the formulation containing oxaliplatin nanomicelle

[0033] Composition Component parts by weight Oxaliplatin 100g P85-TOS 1000g Mannitol 180g lactose 50g Sodium acetate 45g Water for Injection Appropriate amount

[0034] Wherein the preparation of P85-TOS is the same as the preparation of the above-mentioned P123-TOS, wherein P85 refers to Pluronic 85

[0035] Weigh mannitol, lactose and sodium acetate, add 80% water for injection, dissolve and stir evenly, then add the oxaliplatin-P85-TOS copolymer micelles passed through a 250 mesh sieve, dissolve and stir evenly, use 0.1 mol / L hydrochloric acid or 0.1mol / L sodium hydroxide solution to adjust the pH to 6.0, after passing the intermediate inspection, add water for injection to make up to full volume. The solution was sent to a sterile room by a peristaltic pump, filtered through a 0.22 μm microporous membrane until clear, and freeze-dried to obtain a f...

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Abstract

The invention belongs to the field of pharmaceutical preparations, and particularly relates to an oxaliplatin-containing nano-micelle preparation and a medical application thereof. The oxaliplatin-containing nano-micelle preparation contains oxaliplatin and an amphiphilic block copolymer micelle, wherein the hydrophilic segment of the amphiphilic block copolymer micelle is pluronic, and the hydrophobic segment of the amphiphilic block copolymer micelle is tocopherol succinate. The oxaliplatin is effectively loaded through a nano-micelle drug carrier, the drug loading capacity is improved, the impurity content in the product is reduced, meanwhile, product stability is enhanced, and the inhibition effect of the oxaliplatin for cancer cells is remarkably improved.

Description

technical field [0001] The invention discloses an oxaliplatin-containing nano-micelle preparation and its medical application, belonging to the field of pharmaceutical preparations. Background technique [0002] Due to the lack of specificity of distribution in vivo, antineoplastic drugs are more distributed in normal tissues, resulting in significant toxic effects. Tumor tissue has a large gap between vascular endothelial cells, which enhances the permeability of biomacromolecules and nanoparticles. At the same time, tumor tissue has poor lymphatic circulation, which enhances the retention of biomacromolecules and nanoparticles that penetrate into the tumor, which is called the enhanced penetration and retention effect. [0003] Oxaliplatin is developed by Debiopharm in Switzerland and produced and sold by Sanofi in France. It is the third-generation platinum-based anticancer drug first launched in France in October 1996. It is mainly used for the treatment of metastatic co...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K31/555A61K47/26A61P35/00B82Y5/00B82Y30/00B82Y40/00
CPCA61K31/555A61K9/1075A61K47/26A61P35/00B82Y5/00B82Y30/00B82Y40/00
Inventor 柴杰刘路光曲显霖丁继爽
Owner AFFILIATED CANCER HOSPITAL OF SHANDONG FIRST MEDICAL UNIV SHANDONG CANCER INST (SHANDONG CANCER HOSPITAL)
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