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Immunosuppressive agent of advanced higher fatty acid derivative and application thereof

A technology of higher fatty acid and immunosuppressant, which is applied in the field of immunosuppressant of higher fatty acid derivatives and its application, can solve problems such as side effects, and achieve the effect of low toxicity and controllable side effects

Inactive Publication Date: 2010-12-22
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As discussed above, the most commonly used immunosuppressant is CsA, but the use of CsA has many side effects

Method used

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  • Immunosuppressive agent of advanced higher fatty acid derivative and application thereof
  • Immunosuppressive agent of advanced higher fatty acid derivative and application thereof
  • Immunosuppressive agent of advanced higher fatty acid derivative and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Spleen lymphocyte stimulation and assay

[0081] The original record of the experiment is as follows:

[0082] Drug treatment: 1. Take an appropriate amount of the compound in an ampoule, dissolve it with a small amount of 95% ethanol, filter it with a 0.22um filter membrane, and dilute it to a certain concentration with 1640 (Gibco, USA) culture medium before use. 2. Prepare 2mg of Con A (Sigma, USA) with PBS balanced salt solution to make 400ug / ml, and store at -20°C.

[0083] The C57bl / 6 mice were killed by neck dislocation, soaked in 75% alcohol for 1 min, and then the spleen was removed with sterile ophthalmic scissors and ophthalmic forceps. Mash the spleen mechanically, add 3ml of mouse lymphocyte separation medium (good and easy to get, Beijing Daktronics Co., Ltd.), mix well, filter through a filter, transfer to a 10ml centrifuge tube, and cover 500uL of 1640 culture medium on top of the separation medium . Centrifuge at 2000r / min for 30min, take the middle ...

Embodiment 2

[0086] Determination of IL-2, IL-10 and IFN-γ gene expression in splenic lymphocytes, and comparison with clinical immunosuppressant FK-506

[0087] The original record of the experiment is as follows:

[0088] Drug treatment: 1. Take an appropriate amount of the compound in an ampoule, dissolve it with a small amount of 95% ethanol, filter it with a 0.22um filter membrane, and dilute it to a certain concentration with 1640 (Gibco, USA) culture medium before use. 2. Mix 2mg of Con A with PBS balanced salt solution to make 400ug / ml, and store at -20°C. 3. Dissolve 25mg of FK-506 (ALEXIS, Switzerland) in 5ml of PBS, aliquot into 200ul / tube, and store at -20°C in the dark.

[0089] Separation and counting of spleen lymphocytes (same as in Example 1), adding lymphocytes to a 96-well plate, 3 × 10 5 / well, do 6 replicate wells in parallel. Dilute the compound and FK-506 respectively with 1640 culture solution, set the following experimental groups: Compound K (40ug / ml) (Example ...

Embodiment 3

[0100] Determination of T lymphocyte proliferation, compared with the clinical immunosuppressant FK-506

[0101] The original record of the experiment is as follows:

[0102] Drug treatment: 1. Take an appropriate amount of the compound in an ampoule, dissolve it with a small amount of 95% ethanol, filter it with a 0.22um filter membrane, and dilute it with 1640 culture medium to a certain concentration before use. 2. Dissolve 25mg of FK-506 (ALEXIS, Switzerland) in 5ml of PBS, aliquot into 200ul / tube, and store at -20°C in the dark.

[0103] Preparation of stimulatory cells: BALB / c (H-2d) mice were killed by neck dislocation, soaked in 75% alcohol for 1 min, and then the spleen was removed with sterile ophthalmic scissors and ophthalmic forceps. Mash the spleen mechanically, add 3ml of mouse lymphocyte separation medium, mix thoroughly, filter through a filter, transfer to a 10ml centrifuge tube, and cover 500uL of 1640 culture medium on top of the separation medium. Centri...

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Abstract

The invention discloses an immunosuppressive agent of an advanced higher fatty acid derivative, comprising a compound I, i.e. CH3(CH2)m1CH=CH(CH2)n1COR, a compound II, i.e. CH3(CH2)m2CH=CH(CH2)n2CH=CH(CH2)X1COR, a compound III, i.e. CH3(CH2)m3CH=CH(CH2)n3CH=CH(CH2)x2CH=CH(CH2)yCOR, a compound IV, i.e. CH3(CH2)zCOR and pharmaceutically acceptable salts thereof, and one or combination of a solvate or a hydrate. The immunosuppressive agent is suitable for treating or preventing mammal patient diseases, treating mammal inflammation diseases, mammal anaphylactic reaction diseases, mammal T-cell, leukemia and T-cell lymphoma, and mammal diseases, and inhibiting immune response of animals suffering from autoimmunity diseases, inflammatory disorders or graft versus host diseases, and has low toxicity and controllable side effects.

Description

technical field [0001] The present invention relates to an immunosuppressant of a higher fatty acid derivative, in particular to a higher fatty acid compound or a derivative thereof used as an immunosuppressant, which is used in the treatment of immunosuppression, inflammation, transplant rejection and T cell-mediated autoimmune disease Application, the T cell-mediated autoimmune diseases are such as diabetes, multiple sclerosis, arthritis and systemic lupus erythematosus, etc., by giving animals an effective dose of higher fatty acid compounds to treat and / or prevent immune diseases such as autoimmune diseases or Inflammatory diseases, reducing immune rejection of grafts. Background technique [0002] Modulation of the immune system is desirable in many situations, from suppression of autoimmune responses, to control of infectious diseases and suppression of graft / tissue rejection. The main approach to alleviating rejection is pharmacologically suppressing the recipient's ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/164A61K31/16A61K31/121A61P37/06A61P29/00A61P37/08A61P35/02A61P35/00
Inventor 齐志权王永志秦箐邝晓慧
Owner XIAMEN UNIV
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