Taxol submicroemulsion taking cholesterol complex as intermediate carrier

A paclitaxel and cholesterol technology, which is applied in the directions of drug combination, drug delivery, emulsion delivery, etc., can solve the problems of not conforming to the principles of pharmacoeconomics, the cost of preparing submicron emulsions, and the cost of preparing submicron emulsions. Safety, reduced preparation cost, and low bile solids intake

Active Publication Date: 2011-05-11
BEIJING WEHAND BIO PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, for cholesterol as a lipid material, it is generally believed that the daily intake of cholesterol for healthy adults should not exceed 300 mg (equivalent to the amount of cholesterol contained in one egg yolk), but the compound involved in the existing patent and its preparations, calculated according to the ratio of the two 1:1-19, the maximum intake is equivalent to 19 egg yolks, which is obviously high and has potential safety hazards
[0009] 2) The preparation cost of submicron emulsion is high: the submicroemulsion is prepared with the complex as the intermediate carrier. Since the amount of lipid material in the complex is as high as 1 to 19 times that of paclitaxel, the preparation cost of submicron emulsion is significantly increased , does not meet the principles of pharmacoeconomics;
[0010] 3) The encapsulation efficiency of the submicron emulsion is low and the stability is poor: the single drug dose of paclitaxel is 135-200 mg / m3 clinically 2 , that is, the total amount of each drug per person is about 240-320mg
Further increase the amount of cholesterol, the solubility tends to be stable, no further increase

Method used

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  • Taxol submicroemulsion taking cholesterol complex as intermediate carrier
  • Taxol submicroemulsion taking cholesterol complex as intermediate carrier
  • Taxol submicroemulsion taking cholesterol complex as intermediate carrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Embodiment 1 paclitaxel cholesterol complex

[0051] A total of 6 groups of complexes were prepared, wherein the amount of cholesterol in complexes 1 and 2 was within the range required by the present invention, that is, the paclitaxel / cholesterol weight ratio was between 1:0.09 and 1:0.90; complexes 3 to 6 The amount of cholesterol is higher, beyond the range required by the present invention, specifically 1: 1.37 ~ 1: 9.06. Compounds 3 to 6 were used for subsequent emulsion encapsulation preparation and comparative study of encapsulation. The composition of the above 6 groups of paclitaxel / cholesterol complexes is shown in the table below.

[0052] Table 1: Composition of paclitaxel / cholesterol complex

[0053] Compound number

Paclitaxel

cholesterol

Paclitaxel / cholesterol (weight ratio)

Complex 1

8.0g

3.6g

1∶0.45

Complex 2

8.0g

7.2g

1∶0.90

Complex 3

3.0g

4.11g

1∶1.37

Comple...

Embodiment 2

[0056] Embodiment 2: Paclitaxel submicroemulsion with paclitaxel cholesterol complex as intermediate carrier

[0057] [Prescription Composition]

[0058]

[0059]

[0060] *Complex 1 is paclitaxel / cholesterol complex 1 prepared in Example 1.

[0061] [Preparation]

[0062] Take about 130-140ml of water for injection, add egg yolk lecithin, poloxamer (188) and glycerin according to the prescribed amount, disperse in a tissue grinder to make a uniform water phase, heat to 40°C, and keep warm;

[0063] Measure soybean oil according to the prescription, preheat it to 40°C, weigh the paclitaxel-cholesterol complex 1 prepared in Example 1, dissolve it in the preheated soybean oil, disperse it in a tissue grinder to form a uniform oil phase;

[0064] Under stirring conditions, slowly add the water phase to the oil phase, cut at 10,000 rpm for 5 min to form uniform colostrum, quickly transfer to a high-pressure homogenizer, homogenize 6 times, collect all the emulsion, and...

Embodiment 3

[0066] Embodiment 3: Paclitaxel submicroemulsion with paclitaxel cholesterol complex as intermediate carrier

[0067] [Prescription Composition]

[0068]

[0069] *Complex 2 is paclitaxel / cholesterol complex 2 prepared in Example 1.

[0070] [Preparation]

[0071] Take about 130-140ml of water for injection, add poloxamer (188) and glycerin according to the prescription amount, disperse in a tissue grinder to make a uniform water phase, heat to 80°C, and keep warm;

[0072] Measure soybean oil according to the prescription, preheat to 80°C, weigh compound 2 and egg yolk lecithin according to the prescription, add it to the preheated soybean oil, disperse and dissolve in a tissue masher to make a uniform and transparent oil Mutually;

[0073] Under stirring conditions, slowly add the water phase to the oil phase, cut at 20,000 rpm for 10 min to form uniform colostrum, quickly transfer to a high-pressure homogenizer, homogenize 6 times, collect all the emulsion, and ...

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Abstract

The invention discloses a taxol submicroemulsion. The submicroemulsion comprises taxol-cholesterol complex, injection oil, injection water, emulsifier, assistant emulsifier and isosmotic agent, wherein the weight ratio of taxol to cholesterol in the taxol-cholesterol complex is (1: 0.09) to (1: 0.90). The invention also discloses a preparation method and application of the taxol submicroemulsion. The oil-in-water taxol submicroemulsion, the pH value of which is 4 to 6 and the average particle size of which is less than 600nm, is prepared by taking the cholesterol complex as an intermediate carrier through the step of dissolving the cholesterol complex into an oil phase by using the improvement of the drug oil solubility by the cholesterol complex. The taxol submicroemulsion is used for treating malignant tumors and has higher safety and efficiency.

Description

technical field [0001] The invention relates to a paclitaxel submicroemulsion with a cholesterol complex as an intermediate carrier and a preparation method thereof, and also relates to the use of the paclitaxel submicroemulsion, which belongs to the technical field of pharmaceutical preparations. Background technique [0002] Paclitaxel (Taxol) has important antitumor activity and is widely used clinically in the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, head cancer and neck cancer. Because it is almost insoluble in water (0.006μg / ml), paclitaxel injection is currently used clinically It is prepared by dissolving 30 mg of paclitaxel in 5 ml of Cremopher EL (polyoxyethyl castor oil) / ethanol (50:50, V / V) mixed solution. Since the prescription contains a large amount of Cremopher EL, it is easy to cause the release of histamine in the body, leading to severe allergic reactions. For this reason, the following desensitization treatment is require...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K31/337A61K47/44A61P35/00
CPCA61K9/0019A61K9/1075A61K31/337A61K47/28A61K47/44A61P35/00A61K47/50A61K9/107
Inventor 刘玉玲夏学军郭瑞芳汪仁芸王洪亮金笃嘉
Owner BEIJING WEHAND BIO PHARMA CO LTD
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