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Paclitaxel pharmaceutical composition and pharmaceutical preparation, preparation method and application thereof

A solid pharmaceutical preparation, paclitaxel technology, applied in drug combination, drug delivery, pharmaceutical formulations, etc., can solve the problems of paclitaxel slow progress, low solubility, lack of functional salt-forming groups, etc.

Pending Publication Date: 2021-06-25
SINOTHERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, the development of paclitaxel pharmaceutical compositions suitable for oral solid preparations is still slow due to the low water solubility of paclitaxel
Since the pKa of paclitaxel is 11.99, its solubility in water is lower than about 10 μg / ml (reported to be 0.1~<10 μg / ml), and the structure of paclitaxel lacks a functional salt-forming group, so that it cannot be recovered by preparing a salt. Improve solubility
In addition, due to the efflux of the efflux protein P-glycoprotein (P-gp) in the gastrointestinal mucosal cells, the amount of paclitaxel absorbed into the blood is reduced, resulting in a further decrease in the oral bioavailability of paclitaxel (about 2 %)

Method used

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  • Paclitaxel pharmaceutical composition and pharmaceutical preparation, preparation method and application thereof
  • Paclitaxel pharmaceutical composition and pharmaceutical preparation, preparation method and application thereof
  • Paclitaxel pharmaceutical composition and pharmaceutical preparation, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0104] The technical solutions of the present invention will be further described below through specific examples. It should be noted that the embodiments are only illustrative, not limiting the protection scope of the present invention. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0105] All percentages, parts, ratios, etc. herein are by weight unless otherwise indicated.

[0106] Evaluation method for the physical and chemical properties of paclitaxel pharmaceutical composition

[0107] Powder X-ray diffraction (X-RD): take appropriate amount of paclitaxel bulk drug, physical mixture, and contrast composition or pharmaceutical composition of the present invention respectively, under the condition of Cu target, 45kv voltage, 45mA electric current, record their powder X-ray diffraction pattern (D8ADVANCE X-ray diffractometer manufactured by BRUKER).

[0108] Determination of apparent solubility: Weigh the excess pharm...

Embodiment 1

[0142] Embodiment 1 paclitaxel-HPMCAS pharmaceutical composition / physical mixture (the present invention)

[0143] 1. Preparation

[0144] 1) Composition:

[0145] The specific composition of the paclitaxel-HPMCAS pharmaceutical composition / physical mixture is shown in Table 2-1.

[0146] 2) Preparation:

[0147] Paclitaxel-HPMCAS pharmaceutical composition: according to the specific composition and dosage in Table 2-1, paclitaxel and carrier material HPMCAS (specifically AS-M) and optionally Add TPGS respectively into the mixer and mix evenly, and then feed into the hopper of a co-rotating twin-screw extruder (Omicron 12 from India Steer Company); or directly feed the above ingredients according to the specific composition and dosage in Table 2-1 Feed into the hopper of the co-rotating twin-screw extruder. Set the melting temperature of the co-rotating twin-screw extruder to about 140°C, and the screw speed to about 150rpm, cool, crush, and sieve the extruded product a...

Embodiment 2

[0170] The above tests show that, compared with the paclitaxel bulk drug and Comparative Example 1, the pharmaceutical composition of the present invention can significantly improve the solubility and dissolution rate of paclitaxel. Especially when further adding to the pharmaceutical composition of the present invention During TPGS, the dissolution rate of the pharmaceutical composition was greatly improved, indicating that the carrier material HPMCAS and TPGS has a synergistic solubilizing effect on pharmaceutical compositions. The pharmacokinetic research of embodiment 2 paclitaxel-HPMCAS pharmaceutical composition of the present invention

[0171] 1. Test preparation

[0172] Test preparation:

[0173] Tablets of paclitaxel-HPMCAS compositions 2-4 prepared according to Example 1.

[0174] Comparative preparation:

[0175] ORAXOL TM : Paclitaxel oral solution (ClinicalTrials.gov, clinical trial number NCT01967043) used in Phase I clinical trials, wherein every ml of...

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Abstract

The invention relates to a paclitaxel pharmaceutical composition and a pharmaceutical preparation, a preparation method and application thereof. The pharmaceutical composition comprises paclitaxel serving as an active ingredient and a hydroxypropyl methyl cellulose derivative serving as a carrier material. The pharmaceutical preparation is in the form of an oral solid preparation. The pharmaceutical composition and the pharmaceutical preparation thereof can be used for preparing drugs for preventing and treating malignant tumors and related diseases of mammals.

Description

[0001] This application is a divisional application of the Chinese patent application No. 201780009322.4 filed on February 3, 2017 with the title of "a paclitaxel pharmaceutical composition and its pharmaceutical preparation, preparation method and use". technical field [0002] The present invention relates to a paclitaxel pharmaceutical composition and its pharmaceutical preparation, preparation method and application, in particular to a pharmaceutical composition containing paclitaxel as an active ingredient and the pharmaceutical preparation, preparation method and application of the pharmaceutical composition. Background technique [0003] Paclitaxel (PTX) is a natural alkaloid extracted from Taxus genus, its chemical name is 5β,20-epoxy-1,2α,4,7β,10β,13α-hexahydroxytaxane-11- En-9-one-4,10-diacetate-2-benzoate-13[(2'R,3'S)-N-benzoyl-3-phenylisoserine ester], the structural formula is as follows: [0004] [0005] Paclitaxel is a new type of anti-microtubule drug, wh...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/337A61K47/38A61K47/22A61P35/00
CPCA61K31/337A61K47/22A61K47/38A61P35/00A61K9/0053
Inventor 万建胜方云李坤
Owner SINOTHERAPEUTICS