Active substance of oxidized low density lipoprotein derivative for treating arterial thrombus form

A technology of low-density lipoprotein and active substances, which is applied in the field of active substances for the treatment of arterial thrombosis by oxidized low-density lipoprotein derivatives. , weaken the effect of arteriosclerosis and thrombosis

Inactive Publication Date: 2006-09-20
DALIAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] Chinese patent 99814030.9 uses oxLDL, β 2 -GPI and heat shock protein composition orally induce immune tolerance to treat vascular diseases, however, the oxLDL in the orally inducing immune tolerance drug uses intact oxLDL particles, and its active derivative is lysolecithin However, β 2 -What structural site is mediated by the binding of GPI to oxLDL remains unclear
Potential adverse effects when immunizing with intact oxLDL when using particles containing large amounts of structures that elicit an atherogenic immune response

Method used

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  • Active substance of oxidized low density lipoprotein derivative for treating arterial thrombus form
  • Active substance of oxidized low density lipoprotein derivative for treating arterial thrombus form
  • Active substance of oxidized low density lipoprotein derivative for treating arterial thrombus form

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1: oxLig-1 induces immune tolerance in mice with antiphospholipid syndrome:

[0064] NEW x BXSB(WB)F1 male mouse, a systemic lupus erythematosus-like experimental mouse model with antiphospholipid syndrome-like symptoms, this mouse produces anti-CL antibodies, and anti-CL antibodies increase with age Antibody titers also increased.

[0065] Mice were divided into 3 groups: 10 mice per group.

[0066] Blank group: 10 12-week-old F1 mice, without any oral substance experiment;

[0067] Control group: mice were fed 5 doses of Tween 80: water (1:8) every other day

[0068] oxLig-1 group: mice were fed with 5 doses of 1 mgoxLig-1 dissolved in Tween 80:water (1:8) every other day.

[0069] The above three groups were sacrificed by taking blood from the orbit 5 weeks later. The above three autoantibodies were mainly detected to observe the immune tolerance.

[0070] The results showed that oxLig-1 induced oral immune tolerance in systemic lupus erythematosus-like e...

Embodiment 2

[0071] Example 2: oxLig-1 inhibits the induction of immune tolerance caused by high-fat food:

[0072] LDL-RD (LDL-receptor-deficient mice, Jackson), fed mice with high-cholesterol food containing cholic acid for about 4 weeks, the mice will suffer from hyperlipidemia and obvious atherosclerosis. The mice were divided into 3 groups with 10 mice in each group.

[0073]Blank group: Mice were not fed anything before starting the diet.

[0074] Control group: mice were fed 5 doses of Tween 80: water (1:8) every other day

[0075] oxLig-1 group: mice were fed with 1 mg oxLig-1 dissolved in Tween 80:water (1:8) every other day.

[0076] The above two groups were killed after 5 weeks, and the main detection of serum lipid distribution, cell morphology observation, anti-β 2 - ELISA assay of GPI-oxLig-1 complex antibody, etc.

[0077] The results showed that the serum VLDL and LDL cholesterol levels of the mice in the blank group and the control group were significantly increased, ...

Embodiment 3

[0078] Example 3: oxLig-1 and β 2 -GPI mixtures induce immune tolerance in mice with antiphospholipid syndrome:

[0079] The experimental procedure is the same as the induction procedure and detection index of oxLig-1 mice with antiphospholipid syndrome.

[0080] The results showed that oxLig-1 and β 2 The mixture of -GPI induces oral immune tolerance in systemic lupus erythematosus-like experimental mice, and also significantly reduces the titers of the above three autoantibodies ( image 3 ).

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Abstract

An orally taken medicine for treating arteriosclerosis and thrombosis is prepared from the oxidative low-density lipoprotein derivative, which is an omega-COOH series derivative with 7-ketocholesterol ester structure and the optional beta 2-GPI. It has high stability.

Description

Technical field: [0001] The invention relates to an oxidized low-density lipoprotein series derivative used for treating arterial thrombosis, and can also be used for treating autoimmune diseases such as antiphospholipid syndrome or arterial thrombosis. Further active substances involved are: [0002] (1), 7-ketocholesteryl-9-carboxynonanoate; (oxLig-1) [0003] (2), 7-ketocholesteryl-13-carboxytridecanoate; (13-COOH-7KC) [0004] (3), 7-ketocholesteryl-12-carboxy (keto) dodecanoate (oxLig-2) technical background: [0005] Immune tolerance is a phenomenon in which the body's immune system shows no response or low response to specific antigens re-exposed. The body usually exhibits self-tolerance to self-antigens. The collapse of the body's autoimmune tolerance produces autoantibodies and other autoimmune responses, forming autoimmune diseases. In autoimmune disease, oral tolerance is an immunological term used to describe a weakened immune response in autoimmune disease....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/575A61K9/127A61P9/10A61P7/02
Inventor 刘庆平刘华
Owner DALIAN UNIV
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