Gel injection combining molecular targeted drug and cytotoxic drug

A technology of molecular targeted drugs and gel injections, which is applied in the direction of drug combinations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., to achieve low toxicity, high therapeutic effect, and good stability

Active Publication Date: 2015-05-20
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Combining molecular targeted drugs and traditional cytotoxic drugs for local administration is expected to produce better therapeutic effects, but there is no report in the prior art on which dosage form and how to administer it will produce good results

Method used

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  • Gel injection combining molecular targeted drug and cytotoxic drug
  • Gel injection combining molecular targeted drug and cytotoxic drug
  • Gel injection combining molecular targeted drug and cytotoxic drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Embodiment 1, preparation of lapatinib microparticles and paclitaxel nanoparticle gel injection

[0053] (1) Preparation of lapatinib microparticle suspension: Weigh 60 mg of lapatinib and dissolve it in 1 ml DMSO, take 200 μl, and inject the drug solution into distilled water under ice bath under the condition of ultrasonic probe to prepare After the obtained medicinal solution is suction-filtered, it is re-suspended with an appropriate amount of distilled water (final concentration is 8 mg / ml), and ultrasonically dispersed with a short-term probe to obtain a lapatinib microparticle solution.

[0054] (2) Preparation of Paclitaxel Nanoparticles Suspension: Weigh 32mg Paclitaxel and 160mg Pluronic F127 respectively, add 4ml of chloroform, and ultrasonically dissolve it completely, blow the organic solvent to dryness by nitrogen at a constant flow rate, and place 25°C in a vacuum oven for 12 hours to remove residual organic solvents. Add 8ml of deionized water to the dr...

Embodiment 2

[0056] Embodiment 2, the preparation of imatinib liposome and Taxol gel injection

[0057] (1) Preparation of imatinib liposomes: take a certain amount of lipid material (EPC: Chol: DSPE-PEG2000 = 57:38:5, m / m / m) dissolved in chloroform, and at 37 ° C Vacuum rotary evaporation film formation. Afterwards, a certain amount of 300 mM ammonium sulfate solution was added for hydration, and a water bath was sonicated at 37° C. for 20 min to prepare blank liposomes. Pass through the column to remove free ammonium sulfate, and then incubate with a certain amount of imatinib (lipid material: imatinib=15:1, w / w) at 37°C for 60 min, pass the unencapsulated free drug to remove . Prepare a final concentration of 2 mg / ml.

[0058] (2) It is a commercial preparation of PTX, the concentration is 6mg / ml, and the solvent is ethanol:polyoxyethylene castor oil=1:1.

[0059] (3) Preparation of mixed drug gel injection: Weigh 0.5g Pluronic F127, add to 1ml imatinib liposome solution, 0.5ml ...

Embodiment 3

[0060] Example 3, Preparation of lapatinib and camptothecin mixed polyelectrolyte nanocapsule gel injection

[0061] (1) Preparation of lapatinib and camptothecin mixed polyelectrolyte nanocapsules: camptothecin (40mg), chitosan (6mg) and ammonium bicarbonate (40mg) were added to 30ml of distilled water, stirred for 5min, and cooled The mixed nano-core of camptothecin / chitosan was prepared by ultrasonication in a water bath for 45 min. Then add 4ml of alginic acid (1mg / ml) and sonicate for 25min. Add chitosan and alginic acid solution repeatedly 3 times to prepare camptothecin / (chitosan / alginic acid) 3 Composition, then successively add 20ml of lapatinib (0.5mg / ml) and alginic acid solution under continuous ultrasound to prepare camptothecin / (chitosan / alginic acid) 3 / -lapatinib / alginic acid sample, centrifuge at 10000rpm at high speed for 10min, remove the supernatant, add appropriate amount of solvent to resuspend to an appropriate concentration (camptothecin 4mg / ml, lapat...

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Abstract

The invention relates to a gel injection combining a molecular targeted drug and a cytotoxic drug. The gel injection comprises a small molecular targeted drug, a traditional cytotoxic drug, a temperature-sensitive material, a solvent and pharmaceutical excipients, wherein the temperature-sensitive material is selected from poloxamer, polylacticacid-polyethylene glycol-polylactic acid or polyglycolide lactide-polyethylene glycol-polyglycolide lactide and the like; the solvent is selected from water, brine salt or 5% glucose aqueous solution and the like, the prepared gel injection can be injected intratumorally or peritumorally, the anti-tumor effect is obvious, and the side effects are fewer.

Description

technical field [0001] The present invention relates to a gel injection combining molecular targeted drugs and cytotoxic drugs, in particular to encapsulating a single preparation or a combined preparation of molecular targeted drugs and cytotoxic drugs in a gel formed by a temperature-sensitive material. Or peritumoral injection, to play a local combined treatment effect, belongs to the field of pharmaceutical preparations. Background technique [0002] The treatment of malignant tumors has always been a worldwide problem. With the introduction of the two concepts of radical tumor surgery and the integration of chemotherapy into radical surgery in the last century, tumor treatment has made great progress. Since then, the emergence of molecular targeted drugs after the 1990s has been regarded as a new milestone in the human war against cancer, which has enhanced people's confidence in cancer treatment. Ordinary chemotherapeutic drugs fail due to their poor selectivity, high...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/34A61K47/32A61K47/36A61K45/06A61P35/00
Inventor 张华胡宏祥张强王学清代文兵
Owner PEKING UNIV
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