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Application of II type cannabinoid receptor stimulant in preparation of medicine for treating newborn cerebral hemorrhage

A technology of cannabinoid receptors and agonists, applied in the field of neonatal cerebral hemorrhage drugs, can solve the problems of expensive treatment and other tissue damage, and achieve the effect of promoting nerve regeneration and reducing hydrocephalus

Inactive Publication Date: 2016-06-08
THE FIRST AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIVERSITY OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The existing treatment methods generally adopt surgery, which is expensive and easily causes damage to other tissues; there is no effective treatment drug to improve its complications

Method used

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  • Application of II type cannabinoid receptor stimulant in preparation of medicine for treating newborn cerebral hemorrhage
  • Application of II type cannabinoid receptor stimulant in preparation of medicine for treating newborn cerebral hemorrhage
  • Application of II type cannabinoid receptor stimulant in preparation of medicine for treating newborn cerebral hemorrhage

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Effect of Type II Cannabinoid Receptor Selective Agonist (JWH133) on Collagenase-Induced Cerebral Hemorrhage in Neonatal Rats

[0051] Type VII collagenase induced neonatal 7-day (P7) SD rat cerebral hemorrhage with intraventricular hemorrhage (GMH / IVH) model. Using a stereotaxic instrument to micropump collagenase, the needle insertion coordinates are 1.8mm on the mouth side, 1.5mm on the right side, and 2.8mm after the needle tip breaks through the dura mater. Set up sham operation group (i.e. normal SD rats without surgery), normal saline group (peritoneal injection of the same amount of normal saline after operation), JWH133 treatment group (peritoneal injection of JWH133 aqueous solution 1.5 mg / kg, 2 times / day, 7 days in total), 10 animals in each group.

[0052] After 28 days, the 7.0T cranial MRI of SD rats was checked, and the results were as follows: figure 1 shown.

[0053] from figure 1 It can be seen that JWH133 intraperitoneal injection treatment can si...

Embodiment 2

[0057] Effect of Type II Cannabinoid Receptor Selective Agonist (JWH133) on Differentiation of Primary Rat Neural Stem Cells Stimulated by Thrombin

[0058] Pregnant 14.5dSD rats were selected, anesthetized intraperitoneally with 5% chloral hydrate, the peritoneum was opened, the embryos were taken out, the scalp, skull and dura mater were removed, and the rat brain was peeled off. Under a dissecting microscope, the olfactory bulb was taken as the center of the sagittal longitudinal section, and the cerebral cortex was collected. Add proliferation medium (DMEM / F12, bFGF20ng / mL, EGF20ng / mL, 2% B27), filter through a 200-mesh filter, count cells after trypan blue staining, and adjust the number of cells to 1×10 6 / ml, transferred to culture flask, put into 5% CO 2 , Cultivated in a constant temperature incubator at 37°C, and passaged once every three days.

[0059] Take the logarithmic growth NSCs, digest with 0.25% EDTA trypsin for 2min, stop the digestion with 10% DMEM / F12, ...

Embodiment 3

[0062] Minocycline, also known as "minocycline" or "minocycline", is a broad-spectrum antibacterial tetracycline antibiotic with pharmacological properties such as long half-life and lipophilicity.

[0063] Due to the blood-brain barrier in the brain, direct administration of JWH133 is not easy to enter the brain to realize its function.

[0064] Type VII collagenase induced neonatal 7-day (P7) SD rat cerebral hemorrhage with intraventricular hemorrhage (GMH / IVH) model was the same as before, divided into sham operation group, normal saline group, JWH133 alone group and JWH133+minocycline group, medication After 3 days, the brain water content of the young mice was detected. The result is as Figure 4 shown.

[0065] from Figure 4 It can be seen that the curative effect of JWH133 combined with minocycline in the treatment of neonatal cerebral hemorrhage is better than that of intraperitoneal injection of JWH133 alone.

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Abstract

The invention relates to the field of medicine for treating newborn cerebral hemorrhage, in particular to application of II type cannabinoid receptor stimulant in preparation of medicine for treating newborn cerebral hemorrhage. The application of the II type cannabinoid receptor stimulant in preparation of medicine for promoting nerve regeneration, neural precursor cell differentiation and neural stem cell proliferation after treating newborn cerebral hemorrhage is provided. It is found through tests that the II type cannabinoid receptor stimulant has the effects of promoting newborn nerve regeneration, neural precursor cell differentiation and neural stem cell proliferation; in addition, GMH-induced hydrocephalus can be remarkably reduced. In addition, the II type cannabinoid receptor stimulant is used in cooperation with minocyline which can remarkably increase transmittance of the blood brain barrier of the II type cannabinoid receptor stimulant and add the anti-inflammation effect treatment effect.

Description

technical field [0001] The present invention relates to the field of neonatal cerebral hemorrhage drugs, in particular, relates to the preparation of type II cannabinoid receptor agonists to promote nerve regeneration, neural precursor cell differentiation, neural stem cell proliferation and reduce hydrocephalus drugs after treating neonatal cerebral hemorrhage in the application. Background technique [0002] Germinal matrix-intraventricular hemorrhage (GM-IVH) in premature infants is the most common type of neonatal intracranial hemorrhage. And diagnosis depends on imaging examination. GM-IVH can cause complications such as periventricular hemorrhagic infarction, posthemorrhagic hydrocephalus, leukomalacia, and cerebellar hemorrhagic injury, which is the main cause of neonatal death and poor prognosis of survivors. [0003] The existing treatment methods generally adopt surgery, which is expensive and easily causes damage to other tissues; there is no effective treatment...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61K45/06A61K31/65A61P25/00A61P9/10
CPCA61K9/0019A61K9/08A61K9/19A61K9/2059A61K9/4866A61K31/352A61K31/65A61K45/06A61K47/10A61K2300/00
Inventor 唐俊朱刚陶一浩陈前伟谭亮姜兵
Owner THE FIRST AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIVERSITY OF PLA
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