A kind of talazoparib pharmaceutical composition and application thereof

A composition and drug technology, applied in the field of cancer treatment, PARP enzyme inhibitor Talazoparib pharmaceutical composition, can solve the problems of inability to maintain blood drug concentration for a long time, large fluctuation range of blood drug concentration, and no patent for public preparations, etc., to achieve high efficiency The effect of low toxicity administration frequency, reduction of adverse reactions, and reduction of toxicity

Active Publication Date: 2022-04-08
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Due to the obvious dose-limiting toxicity and the large fluctuation range of blood drug concentration, the Talazoparib oral immediate-release capsules under research have shown many limitations in the clinical application process: 1) Although the immediate-release capsules can quickly reach the required level of PARP enzyme inhibition The level of blood drug concentration, but the drug is absorbed quickly, the fluctuation range of blood drug concentration is large, and the peak value of steady-state blood drug concentration is several times or even ten times higher than the concentration required for PARP enzyme inhibition, resulting in more serious side effects; 2) higher The dose-limiting toxicity produced by the steady-state plasma concentration wave peak hinders the further increase of the dose, and the large fluctuation range of the plasma concentration prevents the drug from maintaining the blood concentration required for PARP enzyme inhibition in the body for a long time, hindering the further improvement of the drug effect. Improvement; 3) The oral dose of the drug is small, which puts forward higher requirements for the preparation process of the solid preparation
[0009] According to the patent search, there is currently no published patent for preparations related to Talazoparib

Method used

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  • A kind of talazoparib pharmaceutical composition and application thereof
  • A kind of talazoparib pharmaceutical composition and application thereof
  • A kind of talazoparib pharmaceutical composition and application thereof

Examples

Experimental program
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preparation example Construction

[0045] The preparation method of the multivesicular liposome of the present invention adopts conventional methods in the art, such as adopting the double emulsion method, specifically, it needs to include the following 5 steps: (1) first dissolve the lipid component of the prescription amount in easy Volatile organic solvents (usually chloroform or a mixture of chloroform and ether) form an oil phase, and the talazoparib of the prescribed amount is dissolved in water to form a drug-containing aqueous solution (the first water phase), and then with a suitable oil-water volume ratio (volume ratio) 1:10-12:10, v / v) mix the aqueous solution (the first water phase) containing the drug with the organic phase (oil phase) of the lipid, and ultrasonically or mechanically shear at room temperature for a certain period of time to prepare a uniform Water-in-oil (W / O) type colostrum; (2) absorb the formed W / O type colostrum, and inject the second aqueous phase buffer solution according to a...

Embodiment 1

[0088] Example 1 Preparation of talazoparib in situ precipitation type gel preparation

[0089]

[0090] Weigh the prescribed amount of PLA (with a molecular weight of 10,000) into N-methylpyrrolidone, stir to dissolve, then add the drug talazoparib and stir slowly until the drug dissolves and becomes uniform, and the talazoparib in-situ precipitation gel injection is obtained.

[0091] Take the gel preparation and place it in a vial filled with 0.5% Tween 80 aqueous solution, cover and seal it, and place it in a constant temperature water bath shaker at 37°C with a rotation speed of 50rpm and an amplitude of 24mm. Samples were taken at the set time points, the sampling volume was 3ml, and a corresponding amount of constant-temperature distilled water was added at the same time. After the released samples were diluted reasonably, the 0.5% Tween 80 aqueous solution was used as a blank, and the ultraviolet-visible spectrophotometry was used. Measured, calculated Cumulative re...

Embodiment 2

[0093] The preparation of embodiment 2 talazoparib microspheres

[0094]

[0095] Dissolve Talazoparib and PLGA in dichloromethane (50ml), and inject it into the BUCHI B- 290 spray drying electrostatic collection system to prepare microspheres with uniform particle size, and 80% of the microspheres have a particle size of 0.5-10 μm.

[0096] Take talazoparib microspheres and place them in the release medium of physiological isotonic PBS solution (pH 7.4) containing 0.2% Tween 80, and incubate at 37°C, under the condition of 100r / min, at the predetermined time point, take 5ml of the dissolution medium, and centrifuge at 10000rpm for 5min Finally, 20 μl of the supernatant was accurately measured and injected into the liquid chromatograph, the chromatogram was recorded, and the drug cumulative release curve was drawn.

[0097] see results figure 2 , the sustained-release microspheres released less than 20% of the talazoparib within 1 hour, released about 20% within 120 hour...

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Abstract

A pharmaceutical composition comprising the PARP inhibitor Talazoparib and its use for treating tumors, the composition specifically comprises (parts by weight): Talazoparib 0.1-200, release rate regulating adjuvant 0.1-500, small molecule regulator 0 ‑1000, pharmaceutical injectable solvent 0‑2000. The composition can sustainably maintain the effective blood concentration of Talazoparib and the inhibitory level of PARP enzyme activity in vivo.

Description

technical field [0001] The present invention relates to the field of pharmaceutical preparations and the field of biology, in particular to a pharmaceutical composition of PARP enzyme inhibitor Talazoparib applied to tumors and its application for treating cancer. The pharmaceutical composition has a controllable release behavior and can maintain Stable in vivo plasma concentration and long-lasting PARP enzyme inhibitory activity. Background technique [0002] Talazoparib is a new PARP inhibitor obtained by Pfizer after acquiring the biopharmaceutical company Medivation, Inc. in August 2016. The molecular formula of Talazoparib is C 19 h 14 f 2 N 6 O, with a molecular weight of 380.35, has the following chemical structure: [0003] [0004] Thousands of DNA damages occur in each cell of the human body every day. There are two types of DNA damage, single-strand breaks and double-strand breaks. PARP (polyadenosine diphosphate-ribose polymerase) mainly repairs single-st...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K9/127A61K9/10A61K9/06A61K31/5025A61K47/34A61K47/44A61K47/26A61K47/10A61K47/24A61P35/00
CPCA61K47/10A61K47/24A61K47/26A61K47/34A61K47/44A61K9/0002A61K9/0019A61K9/0024A61K9/06A61K9/10A61K9/127A61K9/16A61K31/5025A61P35/00
Inventor 甘勇朱全垒郭仕艳朱春柳张馨欣宋文艺
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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