Preparation of solid dispersions and oral preparations of paclitaxel and homologous compounds thereof

A technology of solid dispersion and paclitaxel, which is applied in the field of medicine, can solve the problems of clinical application limitations, achieve the effect of tumor suppression, improve oral bioavailability, and improve the effect of bioavailability

Inactive Publication Date: 2013-05-08
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Docetaxel (also known as docetaxel) is a chemical homologue of paclitaxel, only a small part of the functional group is different, the physical and chemical properties are similar, and some paclitaxel homologues are similar in structure to paclitaxel, and all have the above shor

Method used

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  • Preparation of solid dispersions and oral preparations of paclitaxel and homologous compounds thereof
  • Preparation of solid dispersions and oral preparations of paclitaxel and homologous compounds thereof
  • Preparation of solid dispersions and oral preparations of paclitaxel and homologous compounds thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: Preparation of Paclitaxel-HPMCAS-LG solid dispersion microspheres (without micronized silica gel)

[0035] Weigh paclitaxel (0.1, 0.3, 0.8g) and hypromellose acetate succinate (HPMCAS-LG) (1.9g, 1.7g, 1.2g) (Japan Shin-Etsu Chemical Co., Ltd.) (General Pharmaceuticals and Polymers) Amount 2g) In a 50mL Erlenmeyer flask with a ground mouth, add 3 ~ 8mL acetone and 3 ~ 6mL dichloromethane, and magnetically stir until completely dissolved. The drug-polymer solution is formed under magnetic stirring. Use distilled water containing 0.05% ~ 0.15% surfactant sodium lauryl sulfonate as a poor solvent, and place 250 mL in a cylindrical preparation container. Under the stirring of a propeller stirring blade (500 ~ 700 rpm), slowly add the above suspension to the poor solvent. Once the suspension is poured into the poor solvent, translucent emulsion droplets are formed. As the dichloromethane and acetone continue to diffuse into the poor solvent, the emulsion droplets gr...

Embodiment 2

[0040] Example 2: Paclitaxel-hypromellose phthalate (HP55) solid dispersion microspheres (without micronized silica gel)

[0041] Weigh paclitaxel (0.1, 0.3, 0.7g) and HP55 (1.9g, 1.7g, 1.3g) (Japan Shin-Etsu Chemical Co., Ltd.) (the total amount of drug and polymer is 2g) into a 50mL Erlenmeyer flask with a grinding mouth. Add 3 ~ 5mL acetone and 6 ~ 8mL dichloromethane, magnetically stir until completely dissolved, and form a drug-polymer solution under magnetic stirring. Other preparation methods are the same as in Example 1. The overall recovery rate is 60 ~ 85%. The obtained preparations are named F4, F5, F6, and the drug content in the prescription is about 5%, 15%, and 35%.

[0042] It can be seen from Table 2 that using hypromellose phthalate (HP55) as a solid dispersion carrier can also achieve better oral bioavailability. As the proportion of drug content in the solid dispersion increases, Tmax decreases, but there is no significant difference between F5 and F6. by f...

Embodiment 3

[0046] Example 3: Paclitaxel - Preparation of HPMCAS-LG (or HP55) solid dispersion (without micro-powder silica gel, solvent evaporation method)

[0047] Weigh 100 mg of paclitaxel and mix them with polymer materials HPMCAS-LG (300 mg) and HP55 (300 mg) (the total amount of drugs and polymer in each prescription is 400 mg), and add them to a mixed solvent of 2 mL acetone and 2 mL dichloromethane. After dissolving, spread it evenly on the glass plate. Place in an oven at 45°C for 12 hours to allow the organic solvent to evaporate to dryness. Remove the solid dispersion mixture with a blade, and the obtained preparations are F7 and F8 respectively, and the drug content in the prescription is 25%. It can be seen from Table 3 that the simple solvent evaporation method can also obtain better oral bioavailability. This shows that the combination of drugs and appropriate polymers is one of the key factors to improve the oral bioavailability of drugs.

[0048]

[0049] table Pharmaco...

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Abstract

The invention relates to preparation of solid dispersions and oral preparations of paclitaxel and homologous compounds thereof, wherein solid dispersions and solid dispersion microspheres are prepared to increase rapid release and oversaturation maintenance of paclitaxel and homologous compounds thereof so as to increase bioavailability. According to the present invention, a carrier is hydroxypropylmethylcellulose acetate succinate or hydroxypropylmethylcellulose tetrabutyl titanate, or/and a mixture of hydroxypropylmethylcellulose acetate succinate and micro-powder silica gel or a mixture of hydroxypropylmethylcellulose tetrabutyl titanate and micro-powder silica gel; the drug and macromolecule are dissolved into a mixing solvent of a good solvent and a liquid bridging agent, and the obtained drug-containing solution is slowly added to a poor solvent under a stirring effect; under a shearing force effect of stirring, the drug-containing solution is emulsified and dispersed in the poor agent to form temporary translucent emulsion droplets, the emulsion droplets continuously diffuse to the poor solvent along with the good solvent and the bridging agent, and the drug and the macromolecule in the emulsion droplet are oversaturated so as to gradually solidify to form the solid dispersion microspheres; and the prepared solid dispersion microspheres have characteristics of a size particle of 100-600 mum, a yield of more than 80%, and a drug content of 5-35%.

Description

technical field [0001] The present invention relates to the technical field of medicine, specifically, it selects a type of solid dispersion dispersion carrier, and provides a corresponding preparation method to improve the bioavailability and the The method of efficacy. Background technique [0002] Paclitaxel is a broad-spectrum anticancer drug with definite curative effect, but the drug is extremely insoluble, so the injection prepared by dissolving it in a mixture of surfactant (polyoxyethylene castor oil) and ethanol (1:1) is on the market. The quick onset of the injection is an advantage, but the initial blood concentration is high, which is prone to toxic and side effects, especially paclitaxel injection, which uses a large amount of surfactants, resulting in various adverse reactions, which affect the safety of the drug. Therefore, pharmacists are trying to study oral preparations while reforming injection prescriptions. The oral administration preparations of anti...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K31/337A61K47/38A61P35/00
CPCA61K9/14A61K9/20A61K9/1652A61K31/337A61P35/00
Inventor 崔福德朴洪泽朴洪宇杨亮
Owner SHENYANG PHARMA UNIVERSITY
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