Itraconazole nanometer suspensions lyophilized compound and preparing , using method thereof

Abstract

The invention discloses a freeze-drying combination of itraconazole nanosuspension for injection and preparation and using methods of the nanosuspension. The invention selects serum albumin of the human as main adjunct; itraconazole nano-sized granulation can be successfully realized by adopting the drying technology and freeze drying technology in combined liquid of high pressure homogenization nanometer emulsification technology; and the invention can be filtered to sterilize and can be stored in the form of freeze-dried powder. The itraconazole nanosuspension is prepared in acceptable waterborne diluent in pharmacy, and then the average particle size of the itraconazole nanosuspension is less than 0.3 microns after reconstruction, so the itraconazole nanosuspension can be made into nanosuspension for intravenous injection. The nanosuspension is composed of the following components : the ratio between the itraconazole and albumin is 1 : 200 to 10 : 1; and the nanosuspension also comprises surfactant, stent agent, osmo-regulator and other injection additives, etc. The nanosuspension has the advantages of drug loading, safety, low toxicity, high stability and good warming promotion without hemolysis or stimulation on vein vascular. And the preparation method is simple and easy, and thus the product forming can be realized easily.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a nanosuspension freeze-dried composition for injection of itraconazole and its preparation method and use method. Background technique [0002] Itraconazole is a second-generation triazole synthetic broad-spectrum antifungal drug composed of 4 isomers in equal proportions. It has a highly selective effect on fungal cytochrome P450 and is effective on the skin, mucous membranes and fingers ( Fungus-infected parts such as toe nails and hair have high aggregation, and have a good curative effect on treating diseases caused by fungal infections. It is widely used in superficial and deep fungal infections. It has a broad antibacterial spectrum and good tolerance. The main metabolite hydroxyitraconazole also has high antifungal activity. The drug is effective in the treatment of Aspergillus, systemic Candida and meningeal Good results have been achieved in cryptococcal infection. W...

AI Technical Summary

Problems solved by technology

Chinese Patent Publication No. 1596897 has reported a kind of itraconazole injection and its preparation method; Chinese Patent Publication No. 1739519 has reported a kind of itraconazole injection emulsion and its preparation method; Conazole liposome and preparation method thereof; but, itraconazole is all difficult to dissolve for oil-water two-phase, and clinical dosage is more than 200mg each time, and initial administration is twice every day, generally needs long-term medication, and itraconazole The development and clinical use of injection preparations bring great difficulties

So far, only the injection prepared from the cyclodextrin inclusion complex of itraconazole has been approved for marketing, and it is now on the market in China through import. The price is expensive and the preparation process is complicated. As a solubilizer, dextrin not only aggravates adverse reactions and toxic side effects, but also increases the cost of preparations, inconvenient transportation and storage, cumbersome clinical use, and increased unsafe factors; the drug-loading performance and The stability is not good, the drug is easy to separate out, and there are also problems of increasing the cost of the preparation and inconvenient transportation and storage

Chinese Patent Publication Nos. 1041655 and 1970557 attempt to salt-form itraconazole with sulfuric acid and methanesulfonic acid by changing the salt-forming properties of itraconazole, increasing development costs and uncertainties in efficacy

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