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Medicine composition containing antibody coupling medicine, freeze-drying agent, and preparation method and purpose of medicine composition and freeze-drying agent

A drug and drying technology, applied in the direction of drug combination, drug delivery, anti-tumor drugs, etc., can solve the problem of lack of solubility

Active Publication Date: 2021-03-19
上海复旦张江生物医药股份有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The technical problem to be solved by the present invention is to overcome the defect in the prior art that the F0002-ADC antibody conjugate drug lacks a drug (preparation) composition with good solubility and good stability, and provides a F0002-ADC antibody conjugate drug Pharmaceutical composition, freeze-dried preparation, preparation method and use of combined drug

Method used

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  • Medicine composition containing antibody coupling medicine, freeze-drying agent, and preparation method and purpose of medicine composition and freeze-drying agent
  • Medicine composition containing antibody coupling medicine, freeze-drying agent, and preparation method and purpose of medicine composition and freeze-drying agent
  • Medicine composition containing antibody coupling medicine, freeze-drying agent, and preparation method and purpose of medicine composition and freeze-drying agent

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Effect test

preparation example Construction

[0107] 2.1 Preparation of F0002-ADC

[0108] It can be prepared by conventional methods in the art. For example, F0002-ADC can be prepared according to Method 1 or Method 2 disclosed in Chinese patent document CN201810078006.9. In an embodiment, it is prepared by Example 3 disclosed in Chinese patent document CN201810078006.9.

[0109] 2.2 Main instruments and reagents

[0110] Freeze dryer TELSTAR LyoBeta 6PL; high performance liquid phase analysis system Waters E2695; chromatographic column TOSOHTSKgel G3000SWXL (5μm, 7.8mm×300mm); capillary electrophoresis analysis system Beckman Coulter PA800plus; Calibration instrument MolecularDevices SpectraMax m2e. Citric acid was purchased from Hunan Huari Pharmaceutical Co., Ltd.; sucrose was purchased from Merck; arginine hydrochloride was purchased from Shanghai Concord Amino Acid Co., Ltd.; polysorbate 20 was purchased from J.T.Baker.

[0111] 2.3. Size Exclusion Chromatography (Size Exclusion Chromatography (SEC) Purity Analy...

Embodiment 1

[0122] The formulations and dissolution conditions of each pharmaceutical composition are shown in Table 1. In Table 1, in the formulation of each pharmaceutical composition, the concentration of citric acid-sodium citrate is 10 mM. Some pharmaceutical compositions can significantly improve the solubility of the F0002-ADC drug, and its drug solution is in a clear state, which is conducive to the development of stable preparations. Adding 20-50g / L arginine hydrochloride in the formula is the first choice to improve the solubility.

[0123] The preparation methods of the pharmaceutical composition all include the following steps (except for the final freeze-drying, F0002-ADC is in aqueous solution):

[0124] (1) Configuration of replacement buffer: Mix excipients other than antibodies, including citric acid-sodium citrate, sucrose, arginine hydrochloride, polysorbate 20 or polysorbate 80, and adjust the pH value to meet the table 1 as required;

[0125] (2) Use a 30kD ultrafi...

Embodiment 2

[0132] The water content of each pharmaceutical composition formulation and its freeze-dried preparation is shown in Table 2. In the formulations of each pharmaceutical composition in Table 2, the concentration of polysorbate 20 is 0.2 mg / mL, and the pH value is 5.0. The preparation of each pharmaceutical composition is as described in Example 1.

[0133] The preparation method of freeze-dried preparation is as follows:

[0134] The pharmaceutical composition containing F0002-ADC was divided into injection vials, and the injection vials containing the samples were placed in a LyoBeta 6PL lyophilizer to start lyophilization. Pre-freezing stage: Pre-cool for 1 hour below 5°C. Pre-cool for 1.5 hours below -5°C. Adjust the temperature of the board layer to below -45°C, and control the overall down-regulation rate below 1°C / min, and keep it for more than 2 hours. Slowly increase the temperature of the plate and anneal at no more than -25°C, and keep it for 2 hours. Rapidly coo...

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Abstract

The invention discloses a medicine composition containing an antibody coupling medicine, a freeze-drying agent, and a preparation method and a purpose of the medicine composition and the freeze-dryingagent. The medicine composition comprises the following ingredients in parts by weight: 3-20mg / mL of F0002-ADC, 5-50mM of pH value buffering agents, 10-100mg / mL of protein protection agents, 0.05-2.0mg / mL of surfactant and 0-50mg / mL of arginine hydrochloride of which the pH value is 5-7. The medicine composition (preparation) containing the F0002-ADC antibody coupling medicine greatly eliminatesthe problems that the solubleness of the medicine is low (a medicine solution is under a clear state) and druggability is poor, and the water content of a freeze-drying drying preparation is lowered.A long-term stability experiment verifies that the formula can meet the clinical requirement of the F0002-ADC. The medicine composition or the freeze-drying agent prepared from the medicine composition has a good application prospect in preparation of medicines capable of treating CD30 positive tumors.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a pharmaceutical composition containing F0002-ADC antibody-conjugated drugs, a freeze-dried preparation, a preparation method and an application thereof. Background technique [0002] Lymphoma is one of the top ten malignant tumors in China in terms of morbidity and mortality (Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2): 115-32.), according to the calculation of the National Cancer Center, lymphoma in 2015 There were 88,200 new tumors and 52,100 deaths. Lymphoma is divided into Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). 95% of HL is classical Hodgkin's lymphoma (cHL). The incidence of HL in Europe and America is 2 to 3 cases per 100,000 Humans, accounting for about 20-30% of all lymphomas, are rare diseases (Epidemiology and etiology of Hodgkin's lymphoma Ann Oncol.2002; 13Suppl 4:147-52), while HL is rare in my country, ac...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K47/18A61K47/68A61K31/537A61P35/00
CPCA61K9/19A61K9/0019A61K47/183A61K47/6851A61K31/537A61P35/00Y02P20/55
Inventor 杨彤沈毅珺吴劲松吴光昊张恒宾徐珺郭青松
Owner 上海复旦张江生物医药股份有限公司
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