Pharmaceutical composition of camptothecin derivative and preparation method thereof

A composition and drug technology, applied in the field of medicine, can solve the problems of no preparation, no research on the influence of dosage, solubility and stability, poor stability, etc., achieve a balance between solubility and stability, solve the problem of drug solubility, solve Effects of Stability Issues

Inactive Publication Date: 2012-11-07
CHIA TAI TIANQING PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is a fat-soluble drug, but it has the following problems when it is prepared into an injection preparation: one is that the compound has poor solubility because it is a fat-soluble drug; the other is that the six-membered lactone ring of the compound is easy to open in aqueous solution, Therefore, it has poor stability in aqueous solution, resulting in reduced efficacy
[0007] Although Chinese patent ZL03142241.1 discloses various preparations that can be made into pharmaceutical carriers, and specifically discloses sugars (such as glucose, sucrose, lactose, etc.), no in-depth research has been carried out, including the amount of sugar, other Factors etc. have not been studied on the influence of drug solubility and stability, etc., have not obtained an effective and stable preparation that can solve the above-mentioned contradictions, and other prior art has no report on the preparation of the compound.

Method used

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  • Pharmaceutical composition of camptothecin derivative and preparation method thereof
  • Pharmaceutical composition of camptothecin derivative and preparation method thereof
  • Pharmaceutical composition of camptothecin derivative and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 (+)-(4S)-11-succinyloxyethyl-4-ethyl-4-hydroxyl-1H pyrano[3',4',6,7]indoleazine[1,2 -b] Preparation of quinoline-3,14-(4H,12H)-dione

[0031] Dissolve 1g of 7-hydroxyethylcamptothecin in 40mL of dry dimethyl sulfoxide, add 2g of succinic anhydride, and then add 2mL of dry pyridine, then stir and reflux for 12 hours. The reaction mixture was poured into a separatory funnel, 50 mL of distilled water was added, the aqueous solution was extracted with dichloromethane (200 mL*3), combined, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure. It was separated by silica gel column chromatography and eluted with dichloromethane / methanol 50:1.5 to obtain 840 mg of a light yellow solid (66% yield).

Embodiment 2

[0033] Sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium chloride were dissolved in 500 mL of water for injection, and adjusted to a solution of pH 6.6. Add 25g of lactose to the above solution, stir until it is completely dissolved, then add 0.2% activated carbon to the solution, boil and cool to 60°C for 30 minutes to remove carbon. Add 1 g (calculated as dry product) of the compound of formula 1 into the above decarburized solution, and dissolve until clear. After primary filtration, the medicinal solution is sterilized and filtered through a 0.22 μm filter to obtain a semi-finished product solution. Check the semi-finished product solution to see foreign matter, content and pH. After passing the test, it will be divided into packages, and then put into a freeze-drying box after half-tightening, and then freeze-dried.

Embodiment 3

[0035] Dissolve sodium hydroxide in 500mL water for injection and adjust to pH 7.2. Add 5g of threonine to the above solution, stir until completely dissolved, then add 0.2% activated carbon to the solution, boil and cool to 60°C for 30 minutes to decarbonize. Add 1 g (calculated as dry product) of the compound of formula 1 into the above decarburized solution, and dissolve until clear. After primary filtration, the medicinal solution is sterilized and filtered through a 0.22 μm filter to obtain a semi-finished product solution. Check the semi-finished product solution to see foreign matter, content and pH. After passing the test, it will be subpackaged, and then put into a freeze-drying box after half-tightening, and freeze-dried.

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PUM

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Abstract

The invention relates to a pharmaceutical composition, which comprises (+)-(4S)-11-succinyl oxyethyl-4-ethyl-4-hydroxy-1H pyran[3',4',6,7]indolizine[1,2-b]quinoline-3,14-(4H,12H)-dione or its pharmaceutically acceptable salt, a stabilizing agent and a pH conditioning agent, wherein the pH value is 6.0-7.2.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a pharmaceutical composition of camptothecin derivatives, a preparation method thereof, and an application for treating tumors. Background technique [0002] Camptothecin (CPT) is an alkaloid extracted from Camptotheca acuminata, a plant unique to China, which prevents the replication of cancer cells by selectively acting on DNA topoisomerase I (Top I). Play an anti-cancer role. The applications of camptothecin and hydroxycamptothecin are limited due to their poor solubility and large toxic and side effects. Since the first separation, hundreds of camptothecin derivatives and analogs have been synthesized in the world. The positions of structural modification are mostly at the 7, 9 and 10 carbons of camptothecin. By introducing different substituents at these positions In order to improve drug efficacy, reduce toxicity and improve solubility, etc., the representative drugs t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4745A61K9/19A61K47/26A61P35/00
Inventor 董平左丞陈智林高勇
Owner CHIA TAI TIANQING PHARMA GRP CO LTD
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