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Pegylation modifier of long-acting thymosin alpha1

A modification and compound technology, applied in the field of long-acting thymosin α1 PEGylation modification, can solve the problems of high price, frequent injections and large doses

Inactive Publication Date: 2012-10-31
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Currently clinically used Tα1 is a chemical synthetic product, sterilized dry powder preparation, the clinical dosage for the treatment of chronic hepatitis B is 1.6mg / time, injected 2 times / week, 6 months / course of treatment, with large dosage and frequent injections and expensive disadvantages

Method used

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  • Pegylation modifier of long-acting thymosin alpha1
  • Pegylation modifier of long-acting thymosin alpha1
  • Pegylation modifier of long-acting thymosin alpha1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0138] Example 1: Ac-[Cys 5 (MPEG 5000 -MAL)]Tα1(BTJB005)

[0139] 1.1Ac-[Cys 5 ] Tα1 Synthesis:

[0140] Synthesized by solid phase method [Cys 5 ]Tα1: Take 100mg of Wang resin as the solid carrier, Fmoc-AA-OH (1-10 times the amount) as the raw material, DCC (1-10 times the amount), HOBt (1-10 times the amount) as the condensing agent, divided by Cys 5 Replace Val 5 In addition, the remaining amino acid residues were synthesized according to the Tα1 sequence to obtain Ac-[Cys 5 ] Tα1 fully protected peptide resin. After drying, TFA was cracked and reacted at room temperature for 20-200 minutes. The resin was filtered off, and ether was added to precipitate a white solid, which was dissolved in water and freeze-dried to obtain 161 mg of a white solid. RP-HPLC purification, ESI-MS identification, [M] 2+ Peak: 1551.0 (theoretical value: 3098).

[0141] 1.2Ac-[Cys 5 (MPEG 5000 -MAL)] Synthesis of Tα1

[0142] The purified Ac-[Cys 5 ]Tα1 is dissolved in water, adjust the pH in the range...

Embodiment 2

[0144] Example 2: Ac-[Cys 8 (MPEG 5000 -MAL)]Tα1(BMJB008)

[0145] Synthesize Ac-[Cy s according to the method in Example 1.1 8 ]Tα1, 116mg crude peptide was obtained. RP-HPLC purification, ESI-MS identification, [M] 2+ Peak: 1543.0 (theoretical value: 3083).

[0146] Synthesize Ac-[Cys according to the method of Example 1.2 8 (MPEG 5000 -MAL)] Tα1, the product was separated by HPLC, and freeze-dried to obtain 16.9 mg of white solid, with a yield of 37.1%.

[0147] Ac-[Cys 8 (MPEG 5000 -MAL)] Tα1 was identified by MALDI-TOF-MS, there are a series of peaks near 8247, the molecular weight difference of the two adjacent peaks is about 44, which has the typical structural characteristics of polyethylene glycol.

Embodiment 3

[0148] Example 3: Ac-[Cys 11 (MPEG 5000 -MAL)]Tα1(BMJB011)

[0149] Synthesize Ac-[Cys according to the method of Example 1.1 11 ]Tα1, 143mg of crude peptide was obtained. RP-HPLC purification, ESI-MS identification, [M] 3+ Peak: 1034.9 (theoretical value: 3098).

[0150] Synthesize Ac-[Cys according to the method of Example 1.2 11 (MPEG 5000 -MAL)] Tα1, the product was separated by HPLC and freeze-dried to obtain 21.4 mg of white solid, with a yield of 28.9%.

[0151] Ac-[Cys 11 (MPEG 5000 -MAL)] Tα1 was identified by MALDI-TOF-MS. There are a series of peaks near 8282. The molecular weight difference of the two adjacent peaks is about 44, which has the typical structural characteristics of polyethylene glycol.

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Abstract

The invention relates to a preparation method of a thymosin alpha1 pegylation modifier (Talpha1-PEGs), a medicinal composition containing Talpha1-PEGs, and an application of the medicinal composition to treatment or prevention of relevant diseases such as immunodeficiency or immunologic function immunodeficiency and the like, including an application to the treatment or prevention of relevant diseases such as hepatitis B, hepatitis C, liver cancer, malignant melanoma, non-small cell lung cancer, SARS (Severe Acute Respiratory Syndromes) caused by coronaviruses, acquired immunodeficiency syndrome and the like.

Description

[0001] This application is a divisional application based on the Chinese patent application with the application number 200910207003.1, the application date being November 10, 2005, and the invention title of "Pegylation Modification of Long-acting Thymosin α1". Invention field [0002] The present invention relates to thymosin α1 PEGylated modified substances (Tα1-PEGs), preparation methods of Tα1-PEG s, pharmaceutical compositions containing them, and their use in treating or preventing diseases related to immunodeficiency and low immune function. The use of medication or combination medication, including the treatment of hepatitis B, hepatitis C, liver cancer, malignant melanoma, non-small cell lung cancer, SARS (severe acute respiratory syndrome) caused by coronavirus, AIDS and other related diseases or Application in prevention. Background technique [0003] Thymosin alpha1 (Thymosin alpha1, Tα1) is one of the active peptides secreted by the thymus, with high sequence conserv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K17/08A61K38/22A61K47/48A61P31/20A61P31/14A61P31/18A61P35/00A61K47/60
Inventor 刘克良郄建坤马金波郑建全董泗建周文霞齐春会
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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