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Applications of recombinant high-density lipoprotein in treating hypertensive disorders in pregnancy

A technology for high-density lipoprotein and gestational hypertension, which is applied in the application field of recombinant high-density lipoprotein in the treatment of gestational hypertension, can solve the problems of a large amount of plasma, high production cost, and cannot completely replace HDL therapy.

Active Publication Date: 2017-03-22
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, obtaining natural HDL requires a large amount of plasma, the source of raw materials is limited, and the production cost is high and scale-up is difficult
③Using single-component ApoA-I in HDL replacement therapy cannot realize the diversity of HDL functions and cannot completely replace HDL for treatment

Method used

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  • Applications of recombinant high-density lipoprotein in treating hypertensive disorders in pregnancy
  • Applications of recombinant high-density lipoprotein in treating hypertensive disorders in pregnancy
  • Applications of recombinant high-density lipoprotein in treating hypertensive disorders in pregnancy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Embodiment 1: Preparation of recombinant high-density lipoprotein (rhHDL)

[0023] a. Take 4mg of lecithin and 10mg of vitamin E, dissolve in 0.5ml of absolute ethanol. Inject quickly into 12.1ml of PBS after inhalation with a skin test syringe, N 2 Stir for 15 minutes;

[0024] b. Dissolve 5.4mg sodium cholate in 0.5ml PBS; dissolve 10mg rhApoA-I, 5mg rhApoE and 4mg lecithin in 0.8ml PBS. Add to the above liquid under stirring;

[0025] c. Place at room temperature for 30 minutes; move to 4°C and incubate for 12 hours, each component will polymerize to form rhHDL;

[0026] d. Add the liquid into a protein dialysis bag with a pore size of 10 kD, and fully dialyze the dialysate (PBS) at 4° C. to remove sodium cholate.

[0027] TEM observation of e.rhHDL (see attached figure 1 ).

[0028] The results of transmission electron microscopy showed that vitamin E, various apolipoprotein components, lecithin, cholesterol, etc. were successfully polymerized into spherical r...

Embodiment 2

[0029] Example 2: Effect of rhHDL on placental oxidative stress damage and pregnancy outcome in preeclampsia mice

[0030] 1) Replication of preeclampsia mouse model

[0031] Healthy adult sexually mature ApoE - / - 60, 20 C57BL / 6J, male and female, 8-10 weeks old. Raise them in a barrier system with a room temperature of 20-25°C and a relative humidity of 40%-70%, with 12 hours of day and night lighting, and no restriction on food and water. Male and female mice were caged overnight at 1:00 at 10:00 the night before, and the vaginal suppository was observed before 7:00 the next morning. If the vaginal suppository is observed on the first day of pregnancy, it will be kept in isolation. C57BL / 6J pregnant mice served as the normal control group and were given standard feed; ApoE - / - Pregnant mice were randomly divided into three groups, model control group, rhHDL low-dose group and rhHDL high-dose group, and fed high-fat diet.

[0032] From the 11th day of pregnancy, ApoE - / ...

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Abstract

The invention relates to applications of recombinant high-density lipoprotein in treating hypertensive disorders in pregnancy, and in particular relates to the preparation of recombinant high-density lipoprotein, and applications of the recombinant high-density lipoprotein in producing the medicines for preventing and treating hypertensive disorders in pregnancy. The recombinant high-density lipoprotein has the main features that the protein components comprise two kinds of apolipoprotein, namely, recombinant human apolipoprotein A-I and recombinant human apolipoprotein E which are produced by adopting methylotrophic yeast, and vitamin E replaces cholesteryl ester in natural high-density lipoprotein, and is taken as the core part of the recombinant high-density lipoprotein, so that the recombinant high-density lipoprotein has the strong antioxidant activity.

Description

technical field [0001] The present invention relates to the application of recombinant high-density lipoprotein in treating hypertensive disorder during pregnancy, in particular to the preparation of recombinant high-density lipoprotein and its application in the production of medicines for preventing and treating hypertensive disorder during pregnancy. The main feature of recombinant high-density lipoprotein is that the protein components include recombinant human apolipoprotein A-I and recombinant human apolipoprotein E produced by methylotrophic yeast; vitamin E is used to replace natural high-density lipoprotein Cholesteryl esters, as the core part of recombinant high-density lipoprotein, make it have stronger antioxidant activity. Background technique [0002] Hypertensive disorder of pregnancy (HDCP) is the most common pregnancy complication, which seriously threatens the health of mother and child, and is one of the main causes of maternal death, perinatal morbidity a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P15/00A61P9/12A61K31/355
CPCA61K31/355A61K38/1709A61K2300/00
Inventor 苏曼曼许天敏
Owner JILIN UNIV
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