Itraconazole nanometer suspensions lyophilized compound and preparing , using method thereof

An itraconazole nanometer and nanosuspension technology, applied in the field of medicine, can solve the difficulties in the development and clinical use of itraconazole injection preparations, the poor drug-carrying performance and stability of emulsions and liposomes, and the The problems of development cost and uncertainty of curative effect, etc., achieve the effect of good reorganization and dispersion stability, broad industrialization prospects, and good storage stability.

Inactive Publication Date: 2008-06-18
CHINA PHARM UNIV
View PDF7 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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 throu

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Itraconazole nanometer suspensions lyophilized compound and preparing , using method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] The preparation process of dichloromethane as solvent

[0029] Prepare human serum albumin (HSA) that meets the injection quality requirements into a 3% (W / V) sterile aqueous solution with water for injection, adjust the pH to 5.6 with citric acid, citric acid and some basic groups in albumin Salt formation, stabilization of albumin, stirring and addition of 1.3% dichloromethane to prepare its saturated aqueous solution. 200ml of the albumin solution sterilized in advance was mixed with 4.0ml sterile dichloromethane drug solution under vigorous stirring, and 0.6g (10% of the albumin weight) powdered sterile itraconazole (effectiveness) was dissolved in advance. valence > 99%), using a high-shear mixer to stir the mixture to prepare colostrum, add 6.0 ml of sterile ethanol dropwise, and stir evenly at high speed. Mixture colostrum is controlled preparation temperature in high-pressure homogenizer (suitably sterilized) at 50 ℃, circulates 1 time through 50bar pressure, c...

Embodiment 2

[0032] Preparation process with chloroform as solvent

[0033] Human serum albumin (HSA) meeting the injection quality requirements was prepared into 1.5% (W / V) sterile aqueous solution with water for injection, and the pH was adjusted to 7.0. 200ml of the albumin solution was mixed with 6.0ml of sterile chloroform drug solution under vigorous stirring, and 0.3g (10% of albumin weight) of powdered sterile itraconazole was dissolved in advance. Stir the mixture with a high-shear mixer to prepare colostrum, add 2.0 ml of sterile ethanol, and stir evenly. The colostrum mixture is controlled in a high-pressure homogenizer (suitably sterilized) at a temperature of 50° C., circulated twice at 200 bar, three times at 500 bar, and once at 900 bar until a nanoemulsion is obtained. Introduce it into the round bottom flask of the rotary thin film evaporator under sterile conditions, maintain the temperature of the water bath at 40 ° C, start the vacuum pump, and vacuum rotary evaporatio...

Embodiment 3

[0035] The preparation process of increasing the amount of chloroform

[0036] Human serum albumin (HSA) meeting injection quality requirements was prepared into 3% (W / V) sterile aqueous solution with water for injection, the pH was adjusted to 6.0 with acetic acid and sodium hydroxide, and the aqueous solution was saturated with 1% chloroform. 200ml of the albumin solution is mixed with 8.0ml of sterile chloroform drug solution under vigorous stirring, and the chloroform solution is pre-dissolved with 0.6g (10% of the albumin weight) powdered sterile itraconazole (potency>99 %), using a high-shear mixer to stir the mixture to prepare colostrum, add 2.0ml of sterile ethanol, and stir evenly. The colostrum mixture is controlled and prepared at 50° C. in a high-pressure homogenizer (suitably sterilized), circulated twice at 200 bar and three times at 500 bar until nanoemulsion is obtained. Introduce it into the round bottom flask of the rotary thin film evaporator under sterile...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
The average particle sizeaaaaaaaaaa
Particle sizeaaaaaaaaaa
Login to view more

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...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K31/496A61K9/19A61K47/42A61P31/10
Inventor 周建平张志祥张辉
Owner CHINA PHARM UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap