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Stable CTLA4Ig protein preparation

A preparation and stable technology, applied in the field of CTLA4 molecular preparation, can solve the problems of reduced bioavailability of active protein, changes in pharmacokinetics, unwanted immunogenicity, etc.

Inactive Publication Date: 2015-07-01
SUNSHINE GUOJIAN PHARMA (SHANGHAI) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, high concentrations of protein solutions are more prone to aggregation, which can cause a number of problems, including reduced bioavailability of the active protein, altered pharmacokinetics, and unwanted immunogenicity

Method used

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  • Stable CTLA4Ig protein preparation
  • Stable CTLA4Ig protein preparation
  • Stable CTLA4Ig protein preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1 The impact of the molecular weight of PVP on the soluble CTLA4 molecular protein preparation

[0021] The stability of soluble CTLA4 molecular protein preparations containing PVP with different molecular weights was studied at 25°C. The formulations contained in addition to PVP other excipients according to the details given in Table 1.

[0022] Table 1: Soluble CTLA4 molecular protein preparations containing PVP with different molecular weights

[0023]

[0024] Remarks: In the table, PVP1 (weight average molecular weight 44K-54K Daltons); PVP2 (weight average molecular weight 27K-32K Daltons); PVP3 (weight average molecular weight 2K-3K Daltons); PVP4 (weight average molecular weight 1M- 1.5M Dalton)

[0025] The above sample preparations were incubated at 25°C for one month and then analyzed by SDS-PAGE. SDS-PAGE is used as an analytical technique to separate free and high molecular weight species from native proteins according to their molecular weig...

Embodiment 2

[0033] Example 2 Effect of PVP Content on Soluble CTLA4 Molecular Protein Preparation

[0034] Formulations of CTLA4 molecules containing different amounts of low molecular weight PVP were investigated. The formulations contained, in addition to PVP, other excipients according to the details given in Table 3.

[0035] Table 3: CTLA4Ig preparation ingredient table

[0036]

[0037] CTLA4 molecular protein preparations with different contents of low molecular weight PVP as given in Table 3 were charged at 50 °C for 3 days, and then analyzed by SE-HPLC and differential scanning calorimetry (DSC).

[0038] Table 4: Effects of different contents of low molecular weight PVP on formulation stability

[0039]

[0040] The results showed that the addition of 1% to 20% low molecular weight PVP could better inhibit the aggregation and fragmentation of high-concentration proteins. A more preferred low molecular weight PVP content ranges from 1% to 4% PVP2.

Embodiment 3

[0041] Example 3 Effect of Sugar on Soluble CTLA4 Molecular Protein Preparation

[0042] The effect of different levels of sugar on the stability of CTLA4Ig formulations was evaluated. We placed the samples at -20°C, 8°C and 25°C under the conditions of 60% humidity and detected the aggregation and fragmentation of proteins in CTLA4Ig preparations by SE-HPLC at different time points.

[0043] Table 5: Soluble CTLA4 molecular protein formulation formula table

[0044] CTLA4Ig

150mg / ml

Palosham 188

6mg / ml

Phosphate buffer

10mM

Pvp2

4%

sucrose

See Table 8 for details

[0045] Table 6: Effect of sugar on the stability of soluble CTLA4 molecular protein preparations

[0046]

[0047] It can be seen from Table 6 that sugar has a great influence on the stability of CTLA4Ig preparations. Preferably, when the weight ratio of sucrose:CTLA4Ig is 170:125, the stability is the best.

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Abstract

The invention provides a stable high-concentration CTLA4 molecular pharmaceutical preparation, which contains soluble CTLA4 molecules in a concentration range from 50mg / ml to 250mg / ml and 1-20% of polyvinylpyrrolidone which has the Dalton molecular weight range of 2000-54000, and preferably 1-4% of polyvinylpyrrolidone which has the Dalton molecular weight of 27000-32000. The preparation disclosed by the invention can effectively relieve the aggregation of high-concentration CTLA4 molecular protein.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals, and more specifically, the invention relates to a CTLA4 molecular preparation. Background technique [0002] In recent years, with the rapid development of life science and technology, protein drugs have entered a period of rapid development, and a variety of protein drugs have been approved for marketing. The most common route of drug delivery for proteins is intravenous (IV), however, for products that require frequent and long-term dosing, the subcutaneous (SC) route of administration is more attractive and more convenient for patients. However, the volume of drug solution for SC injection is much smaller than for IV infusion, so the protein must be present at a higher concentration. However, high concentrations of protein solutions are more prone to aggregation, which can cause a number of problems, including reduced bioavailability of active proteins, altered pharmacokinetics, and unwanted...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/32A61K38/17A61P29/00A61P19/02A61P17/06
Inventor 翟志慧黎健荣
Owner SUNSHINE GUOJIAN PHARMA (SHANGHAI) CO LTD
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