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Application of 3,4-dihydroxy-phenyl-lactic acid in preparing medicament for treating microcirculatory disturbance

A technology of microcirculation disorder and phenyl lactic acid, which is applied in the field of medicine, can solve the problems of clearing peroxide with unclear DLA, unclear DLA, etc.

Inactive Publication Date: 2009-07-22
TIANJIN TASLY PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the potential of DLA to scavenge superoxides generated in response to I / R in vivo is unclear, nor is it clear whether DLA can act on I / R-induced superoxides already present

Method used

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  • Application of 3,4-dihydroxy-phenyl-lactic acid in preparing medicament for treating microcirculatory disturbance
  • Application of 3,4-dihydroxy-phenyl-lactic acid in preparing medicament for treating microcirculatory disturbance
  • Application of 3,4-dihydroxy-phenyl-lactic acid in preparing medicament for treating microcirculatory disturbance

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] The preparation of embodiment one experimental material

[0050] animal

[0051] All studies were approved and all experimental animals were handled according to the guidelines of Keio University Animal Research Committee. Male Wester rats weighing 200g-250g (Saitama Experimental Animal Supply Co., Ltd., Saitama Prefecture, Japan) were fasted for 12 hours before the test, but were allowed to drink water freely.

[0052] Reagent

[0053] DLA (chemical formula see figure 1 ) were purchased from China National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Superoxide dismutase (SOD), toluidine blue, fluorescently labeled bovine serum albumin were purchased from Sigma chemical reagent company (Sigma chemical.co) (Missour, USA), dihydrorhodamine 123 (DHR) was purchased from Molecular Probes (Molecular Probes) (Oregon, USA). FITC-conjugated mouse anti-rat CD11b monoclonal antibody, FITC-conjugated mouse anti-rat CD18 monoclona...

Embodiment 2

[0059] Embodiment 2 Experimental scheme

[0060] In the I / R group (I / R), saline solution (6ml / kg / hr) was continuously infused through the jugular vein catheter 10 minutes before ischemia, and kept until the end of the observation. Control animals (Sham) received the same treatment as the I / R group.

[0061] In the DLA preconditioning group (DLA+I / R) or SOD preconditioning group (SOD+I / R), DLA (5mg / kg / hr) or SOD (12000u / kg / hr), and keep it until the end of the observation.

[0062] In the DLA postconditioning group (I / R+DLA) or SOD postconditioning group (I / R+SOD), DLA (5mg / kg / hr) or SOD (12000u / kg / hr), and keep it until the end of the observation.

Embodiment 3

[0063] Embodiment 3 Determination of Experimental Parameters

[0064] Measurement of venule parameters

[0065] Images of venules were acquired with a charge-coupled device (CCD) color camera system (CC-090, Flovel, Tokyo, Japan). The diameter of mesenteric venules was measured by a video measuring gauge (IV-560; Hoei, Tokyo, Japan). During playback of the videotape images, the number of adherent and migrating leukocytes was determined offline. Judging from the replayed video images, leukocytes attached to the same position for more than 30 seconds were determined as adhered leukocytes adhered to the venule wall.

[0066] The number of adhered leukocytes was counted along randomly selected venules (25-40 μm in diameter, 200 μm in length) from recorded videotape images and expressed as number per 200 um of venule length. The movement of leukocytes is expressed as the amount per field of view surrounding the venules.

[0067] To quantify albumin extravasation across the ...

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Abstract

The invention discloses application of 3,4-dihydroxyl-phenyl lactic acid in preparing a medicine treating microcirculatory disturbance. Salvia Miltrorrhiza (SM) is contained in a great number of the prior Chinese medicines used to treat blood vessel diseases, and 3,4-dihydroxyl-phenyl lactic acid(DLA) is one of main active ingredients in the Salvia Miltrorrhiza. The microcirculatory disturbance is mesentery microcirculatory disturbance and is caused by ischemia / reperfusion. The invention also discloses application of the 3,4-dihydroxyl-phenyl lactic acid in preparing a medicine for preventing adhesion of white blood cells caused by the microcirculatory disturbance, a medicine for restoring adhesional white blood cells caused by the microcirculatory disturbance, a medicine for inhibiting exudation of albumin from small veins caused by the microcirculatory disturbance, a medicine for inhibiting degranulation of mast cells caused by the microcirculatory disturbance, a medicine for inhibiting expressions of adersional molecules CD11b and CD18 on neutrophilic granulocytes caused by the microcirculatory disturbance and a medicine for inhibiting generation of peroxides caused by the microcirculatory disturbance.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of 3,4-dihydroxy-phenyl lactic acid in the preparation of medicines for treating microcirculation disturbance caused by ischemia / reperfusion. Background technique [0002] Ischemia / reperfusion (I / R) causes a large number of microcirculatory damage responses, such as increasing the production of oxygen free radicals from epithelial cells, increasing the expression of L-selectin on leukocytes and E-selectin on endothelial cells, Causes fluctuations in leukocytes, increases the expression of CD11b / CD18 on leukocytes and intercellular adhesion molecule (ICAM-1) on endothelial cells. These molecules enable leukocytes to adhere to postcapillary veins, causing the release of oxygen free radicals that cause damage to the vascular endothelium. In addition, postcapillary venules also respond to I / R with mast cell degranulation and release of vasoactive substances, which have been i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/192A61P9/10
Inventor 韩晶岩
Owner TIANJIN TASLY PHARMA CO LTD
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