Temozolomide freeze-dried preparation

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-...

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

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