Temozolomide freeze-dried preparation

A technology of temozolomide and freeze-dried preparations, which is applied in the field of medicinal chemistry, can solve the problems of hidden dangers in the quality and safety of injection preparations, cumbersome operations, and long time, and achieve the effects of conforming to clinical medication habits, reducing toxic and side effects, and stabilizing quality

Active Publication Date: 2010-10-27
JIANGSU AOSAIKANG PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] 1. U.S. Patent USP6251886 discloses a temozolomide injection administered in the form of a micronized suspension, but because the suspension is prone to blockage of blood vessels, the preparation was not successful;
[0011] 2. Chinese patent CN200510014962.3 discloses a temozolomide freeze-dried powder injection, which dissolves temozolomide by adjusting the pH and heating ultrasonically. A large amount of hydrolyzate will be produced during the process; in addition, the formed freeze-dried preparation has poor resolubility and unqualified solution clarity, and the use of this injection preparation has potential quality and safety risks;
Although the lyophilized preparation method shortens the dissolution time of temozolomide, reduces the degradation of the main drug to a certain extent, and increases the stability of the temozolomide solution; After standing for a period of time, the method of re-filtering can solve this problem, but this method has many disadvantages such as waste of some main components, unstable content, cumbersome operation, long time, easy to infect bacteria, etc., and industrial production is difficult to realize and batch repeat

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: Preparation of temozolomide freeze-dried preparation for injection

[0028] (1) Preparation composition:

[0029] Temozolomide 250mg

[0030] L-Alanine 500mg

[0031] Polysorbate 80 400mg

[0032] Mannitol 1.5g

[0033] Sodium citrate 500mg

[0034] Hydrochloric acid 410mg

[0035] Water for injection Add water to make up to 100ml

[0036] (2) Preparation method:

[0037] Weigh the above weight of L-alanine, polysorbate 80, mannitol, sodium citrate, hydrochloric acid, add 80ml of water for injection, stir for about 2 minutes, all the solids are dissolved and clear, add the prescribed amount of temozolomide, stir After about 8 minutes, all the solids were dissolved and clarified. Adjust the pH to 4.0 with hydrochloric acid solution or sodium hydroxide solution; add water for injection to make up the volume to 100ml, filter through a 0.22μm microporous membrane, take 20ml for room temperature solution placement test, and others The solution is divide...

Embodiment 2

[0062] Embodiment 2: Preparation of temozolomide freeze-dried preparation for injection

[0063] (1) Composition:

[0064] Temozolomide 100mg

[0065] L-Alanine Hydrochloride 100mg

[0066] Polysorbate 80 100mg

[0067] Mannitol 0.5g

[0068] Potassium Citrate 100mg

[0069] Hydrochloric acid 50mg

[0070] Water for injection Add water to make up to 100ml

[0071] (2) Preparation method:

[0072] Take by weighing the above-mentioned L-alanine hydrochloride, polysorbate 80, mannitol, sodium citrate, hydrochloric acid, add in 80ml water for injection, stir until all solids are dissolved and clear, add the temozolomide of prescription amount, stir until All the solids are dissolved and clarified, and the pH is adjusted to 6.0 with hydrochloric acid solution or sodium hydroxide solution; add water for injection to make up the volume to 100ml, pass through a 0.22μm microporous filter membrane to sterilize and filter, and divide into 30ml vials, each with 10ml The solution i...

Embodiment 3

[0074] Embodiment 3: Preparation of temozolomide freeze-dried preparation for injection

[0075] (1) Composition:

[0076] Temozolomide 1g

[0077] L-Leucine Hydrochloride 800mg

[0078] Polysorbate 80 600mg

[0079] Mannitol 2g

[0080] Citric acid 700mg

[0081] Hydrochloric acid 300mg

[0082] Water for injection Add water to make up to 100ml

[0083] (2) Preparation method:

[0084] Weigh the above weight of L-leucine hydrochloride, polysorbate 80, mannitol, citric acid, hydrochloric acid, add 80ml of water for injection, stir until the solids are all dissolved and clear, add the prescribed amount of temozolomide, and stir until solid Dissolve completely and clarify, adjust the pH to 6.0 with hydrochloric acid solution or sodium hydroxide solution; add water for injection to make up the volume to 100ml, pass through a 0.22μm microporous membrane filter to sterilize and filter, and divide into 30ml vials, each with 10ml of solution , put into a freeze-drying box, an...

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Abstract

The invention discloses a temozolomide freeze-dried preparation. Every 100ml of the preparation comprises 1 to 2,000 mg of temozolomide, 1 to 2,000 mg of solubilizer, 801 to 2,000 mg of polysorbate, 5 to 5,000 mg of mannitol, 1 to 2,000 mg of buffering agent, 0.5 to 1,000 mg of hydrochloric acid and the balance of water. The preparation of the invention overcomes the shortcomings of slow dissolving speed, poor redissolution, fussy operation and unqualified solution clarity of the freeze-dried preparation, has the technical effects that: the preparation of the invention has high redissolution; solid is completely dissolved to be clear and colorless by adding water into the freeze-dried preparation and shaking slightly; purity is over 99.5 percent and single impurity content is below 0.3 percent by detecting the purity and the content by using HPLC; through stability experimental investigation, relative substances and content of the preparation are not changed remarkably; and quality is stable.

Description

technical field [0001] The invention relates to a temozolomide freeze-dried preparation, which belongs to the technical field of medicinal chemistry. Background technique [0002] Temozolomide (Temozolomide) is an oral cytotoxic alkylating agent antineoplastic drug created by Cancer Research Campaign (UK) / Schering-Plough (U.S.). It is listed on the market for the treatment of malignant glioma that develops or recurs after conventional treatment and as a first-line treatment drug for advanced melanoma that has metastasized; the emergence of temozolomide is a major advance in the treatment of malignant glioma. [0003] Temozolomide (Temozolomide) chemical name is 3,4-dihydro-3-methyl-4-oxoimidazole [5,1-d] and 1,2,3,5-tetrazine-8-carboxamide, chemical structural formula for: [0004] [0005] Molecular formula: C 6 h 6 N 6 o 2 [0006] Molecular weight: 194.15 [0007] The synthesis of temozolomide is well known, see for example: Stevens et al., J.Med.Chem, 27, 196-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K31/4188A61K47/18A61K47/20A61K47/34A61P35/00A61K47/26
Inventor 宗在伟赵俊魏佳李谢
Owner JIANGSU AOSAIKANG PHARMA CO LTD
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