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Alkylating recombinant human serum albumin and preparation and application of medicinal composition thereof

A human serum albumin and drug technology, applied in the direction of inactive components of polymer compounds, etc., can solve the problems of source limitation, no literature and patent reports on nano micelles, etc., to achieve high drug loading and avoid potential virus transmission. Dangerous, high encapsulation effect

Inactive Publication Date: 2011-09-07
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, HSA has the following defects as a drug carrier material: 1) there are potential dangers of various infectious disease pathogens in the blood, especially the spread of viruses such as AIDS and hepatitis B, and serum albumin from human plasma is purified during the purification process. It is inevitable to bring these viruses into the final product; 2) Human serum albumin used clinically is mainly obtained by collecting human blood through graded filtration, so its source is limited by plasma and placenta
[0008] This type of self-assembled nanomicelle based on rHSA has not been reported in any literature or patent

Method used

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  • Alkylating recombinant human serum albumin and preparation and application of medicinal composition thereof
  • Alkylating recombinant human serum albumin and preparation and application of medicinal composition thereof
  • Alkylating recombinant human serum albumin and preparation and application of medicinal composition thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0058] Take 1g of rHSA, dissolve it in water, add 0.5292g of n-butyraldehyde, react at 30°C for 0.5h, then add 10% NaBH 4 or NaCNBH 3 The solution was stirred for 12 hours, adjusted to pH 7.0 with 2 mol / L HCl solution, dialyzed in 10 mM phosphate buffer solution (pH 7.4) for 3 days (MWCO=12000-14000), freeze-dried, and obtained. The results of elemental analysis showed that 56 n-butyl groups were introduced into one rHSA molecular chain.

Embodiment 2

[0060] Take 1g of rHSA, dissolve it in water, add 0.9408g of n-octanal, react at room temperature for 0.5h, add NaBH with a concentration of 10% 4 or NaCNBH 3 The solution was stirred for 12 hours, adjusted to pH 7.0 with 2 mol / L HCl solution, dialyzed in 10 mM phosphate buffer solution (pH 7.4) for 3 days (MWCO=12000-14000), freeze-dried, and obtained. The results of elemental analysis showed that 42 n-octyl groups were introduced into one rHSA molecular chain.

Embodiment 3

[0062] Take 1g of rHSA, dissolve it in water, add 0.2867g of n-decyl aldehyde, react at room temperature for 0.5h, then add 10% NaBH 4 or NaCNBH 3 The solution was stirred for 12 hours, adjusted to pH 7.0 with 2 mol / L HCl solution, dialyzed in 10 mM phosphate buffer solution (pH 7.4) for 3 days (MWCO=12000-14000), and freeze-dried to obtain the obtained product. The results of elemental analysis showed that 9 n-decyl groups were introduced into one rHSA molecular chain.

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Abstract

The invention relates to biodegradable recombinant human serum albumin amphipathic derivatives and preparation and application of a medicinal composition thereof. For the derivatives, alkyl is introduced onto a recombinant human serum albumin skeleton, so that the recombinant human serum albumin skeleton has amphipathy, and is automatically assembled to form nano micelles in water. The biodegradable recombinant human serum albumin amphipathic derivatives have the characteristics that: a medicament can be coated by double interaction between a hydrophobic alkyl (acyl) chain and a recombinant human serum albumin molecular hydrophobic chain and the medicament; and the capability of coating the medicament by using recombinant human serum albumin is obviously improved. Auxiliary materials have high safety. Diseases can be prevented from spreading by protein sources. The biodegradable recombinant human serum albumin amphipathic derivatives can be used as vectors of an organic medicament, an insoluble or slightly soluble medicament and an amphipathic medicament and are used for intravascular or intramuscular injection, oral administration and cavitary or external administration. The medicinal composition has a simple preparation method and a mature process and is suitable for large-scale continuous production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a biodegradable amphiphilic recombinant human serum albumin derivative as a drug carrier, and also relates to a preparation method and application of the carrier. Background technique [0002] Human serum albumin (human serum albumin, HSA) is the most abundant protein in plasma (30-50 g per liter of serum), accounting for about 55% of its total protein mass, with a relative molecular mass of about 66,500. Its average half-life in the human body is 19 days. It is a polypeptide single-chain composed of 585 amino acid residues. The molecule contains 17 disulfide bonds and 1 free sulfhydryl group, and does not contain sugar components. Its isoelectric point is 4.7-4.9. It is an acidic protein and is easily soluble in water. It is stable in an aqueous medium with a pH of 4-9, can be dissolved in 40% ethanol by volume fraction, and can be heated to 60°C for 10 hours without ha...

Claims

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Application Information

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IPC IPC(8): A61K47/42
Inventor 周建平霍美蓉尹晓强邹爱峰李静彭小玲崔蓓王竞
Owner CHINA PHARM UNIV
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