Supported hemoglobin composition and preparation method thereof

A hemoglobin, load-type technology, used in drug combinations, peptide/protein components, blood diseases, etc., can solve the problems of short circulation time, complex process, short time consumption, etc., achieve system stability, solve vasoconstriction, and the method is simple and easy row effect

Active Publication Date: 2015-05-27
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] CN1419936A discloses a hemoglobin microcapsule blood substitute and its preparation method. The microcapsule prepared by the double emulsification method contains one or more polylactic acid monomethoxypolyethylene glycol copolymers and hemoglobin. The preparation method Simple, easy to enlarge, and time-consuming, but the particle size of the hemoglobin microcapsules prepared by this invention is several microns, the particle size is relatively large, and it is easy to be phagocytized by macrophages in the mononuclear phagocyte system, and the circulation time in the body shorter
However, when preparing the hemoglobin oxygen-carrying carrier in this invention, the polymer material needs to be chemically modified, and the hemoglobin is bound to the surface of polyethylene glycol-polyester nanoparticles through haptoglobin, and the process is relatively complicated.

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  • Supported hemoglobin composition and preparation method thereof
  • Supported hemoglobin composition and preparation method thereof
  • Supported hemoglobin composition and preparation method thereof

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Embodiment 1

[0060] In the present embodiment, the polyethylene glycol-poly(lactic-co-glycolic acid) block copolymer nanoparticles loaded with hemoglobin are prepared by the following method, which comprises the following steps:

[0061] (1) Mix 2 mL of polyethylene glycol-polylactic-glycolic acid block copolymer ethyl acetate solution with a concentration of 10 mg / mL and 0.4 mL of an aqueous solution of hemoglobin with a concentration of 120 mg / mL, shake to mix them evenly, and place on ice In a water bath, use an ultrasonic cell disruptor to sonicate the above solution for 3 minutes at 80w to form colostrum;

[0062] (2) Then take 2wt% PVA 7mL and 2wt% F683mL, slowly add dropwise to the primary emulsion described in step (1) with a dropper, shake it to mix it evenly, and in the ice-water bath, use the ultrasonic cell to dissolve the above solution Ultrasound at 250w for 5min with the breaker to form double emulsion;

[0063] (3) Remove the ethyl acetate organic solvent with a rotary eva...

Embodiment 2

[0070] In the present embodiment, the polyethylene glycol-poly(lactic-co-glycolic acid) block copolymer nanoparticles loaded with hemoglobin are prepared by the following method, which comprises the following steps:

[0071](1) Mix 2 mL of a polyethylene glycol-polylactic-glycolic acid block copolymer dichloromethane solution with a concentration of 15 mg / mL and 0.4 mL of a hemoglobin aqueous solution with a concentration of 120 mg / mL, shake them to mix them evenly, and place them on ice In a water bath, use an ultrasonic cell disruptor to sonicate the above solution for 3 minutes at 100w to form colostrum;

[0072] (2) Then take 10mL of 2wt% PVA, slowly drop it into the above-mentioned primary emulsion with a dropper, shake it to mix it evenly, and in an ice-water bath, ultrasonicate the above-mentioned solution at 200w for 5min with an ultrasonic cell breaker to form a complex milk;

[0073] (3) Remove the dichloromethane organic solvent with a rotary evaporator, centrifuge...

Embodiment 3

[0076] In the present embodiment, the polyethylene glycol-poly(lactic-co-glycolic acid) block copolymer nanoparticles loaded with hemoglobin are prepared by the following method, which comprises the following steps:

[0077] (1) Mix 2 mL of polyethylene glycol-polylactic-glycolic acid block copolymer ethyl acetate solution with a concentration of 20 mg / mL and 0.4 mL of hemoglobin aqueous solution with a concentration of 120 mg / mL, shake them to mix them evenly, and place them in an ice-water bath , the above solution was ultrasonicated at 80w for 3min with an ultrasonic cell disruptor to form colostrum;

[0078] (2) Take 7mL of 2wt% PVA and 2wt% of F683mL, slowly add it dropwise into the above-mentioned primary emulsion with a dropper, oscillate to make it mix evenly, and in an ice-water bath, use an ultrasonic cell disruptor again at 250w for the above-mentioned solution Ultrasound for 5 minutes to form double emulsion;

[0079] (3) Remove the ethyl acetate organic solvent w...

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Abstract

The invention relates to a supported hemoglobin composition and a preparation method thereof. The preparation method comprises the following steps: (1) dissolving a carrier polyethylene glycol-poly(lactide-co-glycolide) into an organic solvent, mixing with a water solution of hemoglobin, and carrying out ultrasonic treatment to form primary emulsion; (2) adding a water solution of a surfactant to the primary emulsion obtained in the step (1), mixing and carrying out ultrasonic treatment to form a compound emulsion; and (3) removing the organic solvent, and centrifuging to obtain the supported hemoglobin composition. The supported hemoglobin composition is prepared by a double emulsion method; the method is simple and feasible; the prepared supported hemoglobin composition has oxygen carrying and releasing functions, has rheological characteristics similar to whole blood, is high in stability and good in blood compatibility, and does not cause erythrocyte aggregation; and the carrier material provided by the invention is prepared from abundant raw material, has the advantages of low cost, biocompatibility, biological affinity and no toxicity and is prone to be chemically modified.

Description

technical field [0001] The invention belongs to the field of pharmaceutical compositions, in particular to a loaded hemoglobin composition and a preparation method thereof. Background technique [0002] Blood transfusion plays a pivotal role in surgical medicine and the treatment of war wounds. With the diversification and complexity of human life, the source and safety of blood supply have increasingly become an important content of economic, social and people's livelihood issues. Because blood substitutes have the advantages of "good versatility, high safety, and long shelf life", the research and development of blood substitutes has always been of great significance and has attracted much attention. Among them, hemoglobin-based oxygen carriers (HBOCs) are research hotspots in the field of blood substitutes, which are divided into chemically modified hemoglobin, conjugates of hemoglobin and various enzymes, and hemoglobin loaded with cell-like structures. . Among them, t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K38/42A61P7/08
Inventor 吴雁赵彩艳邵磊厚
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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