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Sorafenib lipidosome freeze-dried injection for injection and preparation method thereof

A technology of sorafenib grease and freeze-dried powder injection, which is applied in the field of medicine, can solve the problems of low solubility of sorafenib, difficulty in avoiding the first-pass effect, aggravating toxic and side effects, etc., so as to reduce the adverse reactions of patients and avoid the first-pass effect, the effect of reducing the economic burden of patients

Inactive Publication Date: 2015-04-22
TIANJIN ZHONGXI MEIHUA BIOMEDICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] At the same time, it is difficult to avoid the first-pass effect of oral drugs, which not only leads to the waste of drugs, but also aggravates the occurrence of the above-mentioned toxic and side effects
However, due to the extremely low solubility of Sorafenib in water, it has not been possible to prepare it for injection application

Method used

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  • Sorafenib lipidosome freeze-dried injection for injection and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] 30mg lecithin, 40mg dimyristyl phosphatidylglycerol, 15mg cholesterol, 15mg PEG-DSPE2000, and 3mg sorafenib were dissolved in chloroform, and the solution was evenly rotated in a round bottom flask on a 25-30oC constant temperature water bath and reduced The organic solvent was evaporated under pressure to allow the lipid to form a uniform film on the bottom inner wall of the flask, which was then placed under vacuum at room temperature for an additional 2 hours. After fully drying, add 2ml of 10mM sodium carbonate, 100mM sodium chloride, and 10mM HEPES buffer (pH 9), and wash the membrane evenly on a 35°C constant temperature water bath until the membrane is hydrated to a milky white liposome suspension. The diameter is about 100nm. 400 mg of sucrose was dissolved in liposomes, filtered through a membrane filter with a pore size of 0.2 μm, added with a lyoprotectant, and freeze-dried.

[0041] After the lyophilized Sorafenib liposome lyophilized powder was stored at r...

Embodiment 2

[0043] Dissolve 400mg soybean lecithin (purity>94% phosphatidylcholine), 600mg dimyristyl phosphatidylglycerol, 200mg cholesterol, 20mg PEG-DSPE2000, 40mg sorafenib in ether. Then add 20ml of isotonic phosphate solution with pH 8 into the above ether solution for emulsification, then remove the organic solvent under reduced pressure, and reduce the particle diameter to about 100nm by ultrasonic probe. Then 2.5 g of sucrose was dissolved in the above solution, filtered through a membrane filter with a pore size of 0.2 μm aseptically, a lyoprotectant was added, the final dispersion was divided into vials, and freeze-dried.

[0044] After the freeze-dried Sorafenib liposome freeze-dried powder was stored at room temperature for 3 months, the liposome encapsulation rate obtained after adding water for injection reconstitution was 90%, and the particle size was 155nm.

Embodiment 3

[0046]100 mg of synthetic phospholipids (purity>94% phosphatidylcholine), 150 mg of dipalmitoylphosphatidylglycerol, 50 mg of cholesterol, and 55 mg of polyethylene glycol PEG-DSPE2000 were dissolved in ether. Add 4ml of isotonic phosphate solution of pH 8.5 into the above-mentioned ether solution for emulsification, then remove the organic solvent under reduced pressure, and reduce the diameter of the particle to about 100nm by ultrasonic probe to complete the preparation of the blank liposome. In addition, 10 mg of sorafenib was dissolved in 4 ml of isotonic phosphate solution of pH 8.5, then fully mixed with blank liposomes, adjusted to pH 7.0 with 200 mM HCl, and then equilibrated in a constant temperature water bath at 37°C for 30-60 min. After equilibration, dissolve 400 mg of sucrose in the above solution, filter it through a membrane filter with a pore size of 0.2 μm, add a lyoprotectant, divide the final dispersion into vials, and freeze-dry.

[0047] After the freeze...

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Abstract

The invention discloses a sorafenib lipidosome freeze-dried injection for injection and a preparation method thereof. The freeze-dried injection is prepared from the following components in molar ratio: 1 mol of sorafenib, 5-60 mol of phospholipid, 1-30 mol of cholesterol, 1-60 mol of phosphatidyl glycerol, 1-10 mol of a polyethylene glycol surfactant and 50-400 mol of a freeze-drying protecting agent. The preparation method comprises the following steps: sequentially dissolving phospholipid, cholesterol, phosphatidyl glycerol, polyethylene glycol surfactant and sorafenib in an organic solvent in proportion; then, carrying out rotary and vacuum evaporation on the obtained organic solution in a round bottom glass bottle, so that a uniform thin film is formed on the inner wall of the glass bottle; then, adding a buffer liquid with the pH of 7-10 into the glass bottle to be continuously stirred to form a suspension; reducing the grain size of the suspension by an ultrasonic or high-pressure homogenizing method; and adding the freeze-drying protecting agent and freeze-drying. The sorafenib lipidosome disclosed by the invention remarkably improves the bioavailability and is stable in property, and the encapsulation efficiency can reach over 96%.

Description

Technical field: [0001] The invention relates to a freeze-dried powder for injection and a preparation method thereof, in particular to a freeze-dried powder for sorafenib liposome injection and a preparation method thereof, belonging to the technical field of medicine. Background technique: [0002] The inhibitory effect of sorafenib on tumor cells is achieved through multiple targets: on the one hand, it can inhibit the activity of serine / threonine protein kinase and tyrosine kinase (RAF / MEK / ERK signaling pathway), thereby directly inhibiting tumor On the other hand, it can slow down tumor angiogenesis by inhibiting human vascular endothelial growth factor receptor and platelet-derived growth factor, so as to indirectly inhibit the growth of tumor cells. Based on the above multi-target mechanism of action, sorafenib has a good effect on the treatment of renal cancer cells and liver cancer cells. [0003] Escudier, Eisen et al. conducted the largest phase III randomized co...

Claims

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Application Information

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IPC IPC(8): A61K9/19A61K9/127A61K31/44A61P35/00
Inventor 刘寅辉李金玲张娜李燕田丽
Owner TIANJIN ZHONGXI MEIHUA BIOMEDICAL TECH
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