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PDGF amphiphilic polymer complex

A technology of amphiphilic polymers and complexes, which can be used in drug combinations, medical preparations with non-active ingredients, digestive systems, etc., and can solve problems such as inability to stabilize protease

Inactive Publication Date: 2008-12-03
ADOCIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Here, the solution enables the stabilization of growth factors in the formulation during product storage, but does not stabilize these growth factors against proteases present in chronic wounds at physiological pH

Method used

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  • PDGF amphiphilic polymer complex
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0149] Example 1: PDGF-BB / DMCBSu complex

[0150] Synthesis of Sulfated Carboxymethyl Dextran (DMCBSu) Modified with Benzylamine

[0151] The amphiphilic polymer is synthesized from carboxymethyl dextran with a degree of carboxymethyl substitution per sugar unit of 1.0 and an average molar mass of 40,000 g / mol. According to the traditional coupling method, benzylamine is grafted onto the acid of this polymer in the presence of water-soluble carbodiimide in water. The degree of benzylamine substitution for each sugar unit is determined by 1 It was determined by H NMR to be 0.4. Then use SO 3 The / pyridine complex sulfates the polymer. The degree of sulfate substitution per sugar unit is 0.3.

[0152] Preparation of PDGF-BB / DMCBSu complex

[0153] Add 10 microliters of 0.1 mg / ml PDGF-BB solution to 90 microliters of 50 mg / ml DMCBSu solution. The PDGF-BB and DMCBSu solutions were buffered at pH 7.4 and 300 mOsm. The solution was stirred gently at ambient temperature for 2 hours and t...

Embodiment 2

[0170] Example 2: PDGF-BB / DMCTrpOMe complex

[0171] Synthesis of carboxymethyl dextran (DMCTrpOMe) modified with tryptophan methyl ester

[0172] The amphiphilic polymer is synthesized from carboxymethyl dextran with a degree of carboxymethyl substitution per sugar unit of 1.0 and an average molar mass of 40,000 g / mol. According to the traditional coupling method, tryptophan methyl ester is grafted onto the acid of this polymer in the presence of water-soluble carbodiimide in water. The degree of tryptophan substitution of each sugar unit is determined by 1 It was determined by H NMR to be 0.3.

[0173] Preparation of PDGF-BB / DMCTrpOMe complex

[0174] Add 10 microliters of 0.1 mg / ml PDGF-BB solution to 90 microliters of 50 mg / ml DMCTrpOMe solution. The PDGF-BB and DMCTrpOMe solutions were buffered at pH 7.4 and 300 mOsm. The solution was stirred gently at ambient temperature for 2 hours and then stored at 4°C.

[0175] Verification of the formation of PDGF-BB / DMCTrpOMe complex

...

Embodiment 3

[0182] Example 3: PDGF-BB / CMCBSu complex

[0183] Synthesis of Sulfated Carboxymethyl Cellulose (CMCBSu) Modified with Benzylamine

[0184] The amphiphilic polymer is synthesized from carboxymethyl cellulose with a degree of carboxymethyl substitution per sugar unit of 1.2 and an average molar mass of 30,000 g / mol. According to the traditional coupling method, benzylamine is grafted onto the acid of this polymer in the presence of water-soluble carbodiimide in water. The degree of benzylamine substitution for each sugar unit is determined by 1 It was determined by H NMR to be 0.2. In SO 3 -Sulfation is carried out in the presence of pyridine complex, and the degree of sulfate radical substitution is 0.30.

[0185] Preparation of PDGF-BB / CMCBSu complex

[0186] Add 10 microliters of 0.1 mg / ml PDGF-BB solution to 90 microliters of 50 mg / ml CMCB solution. The PDGF-BB and CMCBSu solutions were buffered at pH 7.4 and 300 mOsm. The solution was stirred gently at ambient temperature for ...

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Abstract

Pharmaceutical composition with healing activity comprising at least one soluble dextran derivative and at least one platelet-derived growth factor. The present invention relates to a pharmaceutical composition with healing activity comprising at least one soluble dextran derivative and at least one platelet-derived growth factor, and also to the use thereof for the preparation of a medicament with healing action, in particular for use in the treatment of ulcers.

Description

Technical field [0001] The present invention relates to a novel complex of platelet-derived growth factor (PDGF) bound to an amphiphilic polymer, which can improve the in vitro and in vivo physical and chemical stability of therapeutic proteins for pharmaceutical applications. Background technique [0002] PDGFs are glycoproteins of approximately 30,000 Daltons composed of two polypeptide chains connected to each other via two disulfide bridges. Four types of chains have been identified: A, B, C, and D. Natural proteins exist in the form of homodimers or AB-type heterodimers (Oefner C. EMBO J. 11, 3921-2926, 1992). [0003] PDGF was originally isolated from platelets. PDGF is a growth factor released during blood clotting that can promote the growth of various cell types (Ross R et al., Proc. Natl. Acad. Sci. USA, 1974, 71, 1207; Kohler N. & Lipton A ., Exp. Cell Res., 1974, 87, 297). It is known that certain cells other than platelets also produce PDGF, which is mitogenic for mo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61K47/36A61P17/02
CPCA61K38/1858A61K47/36A61P1/04A61P17/02A61P3/10A61K47/30A61K38/18
Inventor G·迪布勒克L·达里-科雷亚J·科雷亚D·迪拉谢尔R·苏拉O·苏拉G·苏拉
Owner ADOCIA
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