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Applications of CB2R (cannabinoid receptor 2) agonist in preparing medicines for treating hypertensive cerebral hemorrhage

A technology of hypertensive cerebral hemorrhage and cannabinoid receptors, applied in the field of preparation of drugs for the recovery of neurological function and cerebral edema after hypertensive cerebral hemorrhage, to achieve the effect of preventing brain atrophy, reducing the degree of edema, and increasing the transmittance

Inactive Publication Date: 2016-06-29
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

So far, there is no research report on JWH133 improving neurological function after hypertensive cerebral hemorrhage

Method used

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  • Applications of CB2R (cannabinoid receptor 2) agonist in preparing medicines for treating hypertensive cerebral hemorrhage
  • Applications of CB2R (cannabinoid receptor 2) agonist in preparing medicines for treating hypertensive cerebral hemorrhage
  • Applications of CB2R (cannabinoid receptor 2) agonist in preparing medicines for treating hypertensive cerebral hemorrhage

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] SD rats (250g-300g) were model animals, and the right femoral artery was dissected and separated, and 200 microliters of autologous arterial blood (without anticoagulant) was taken with a 1ml insulin needle and immediately injected into the right side of the rat through a stereotaxic instrument and a microinjection pump. In the basal ganglia area (slowly inject within 15 minutes), the needle insertion coordinates are 0.2 mm on the mouth side and 2.2 mm on the right side, and the needle tip is inserted 5 mm after breaking through the dura mater. Set up a blank control group (normal SD rats without surgery), a normal saline group (peritoneal injection of the same amount of normal saline after surgery), a JWH133 treatment group (peritoneal injection of JWH133 aqueous solution 1.5 mg / kg, twice a day, 7 days in total) and the type II cannabinoid receptor selective antagonist group (injection of SR144258), 10 animals in each group.

[0045]28 days after the model was establis...

Embodiment 2

[0053] Minocycline, also known as "minocycline" or "minocycline", is a broad-spectrum antibacterial tetracycline antibiotic with pharmacological properties such as long half-life and lipophilicity.

[0054] Due to the blood-brain barrier in the brain, direct administration of JWH133 is not easy to enter the brain to realize its function. After patients took it, it was found that the effect of JWH133 combined with minocycline was significantly better than that of patients who took JWH133 alone.

[0055] In view of this, the following animal experiments were carried out:

[0056] Experimental group 1: Type VII collagenase induced neonatal 7-day (P7) SD rat cerebral hemorrhage with intraventricular hemorrhage (GMH / IVH) model was the same as in Example 1, divided into sham operation group, normal saline group, JWH133 group alone and JWH133+ rice In the nocycline group, the brain water content of young mice was detected after 3 days of administration. The result is as Figure 4 ...

Embodiment 3

[0064] The medicine provided by the present invention includes type II cannabinoid receptor agonist and pharmaceutically acceptable auxiliary materials, and is made into injections, injections, tablets, granules, granules, pills, capsules, suspensions, emulsions, ointments, creams, Transdermal patches, etc.

[0065] The preparation of each dosage form is illustrated as follows:

[0066] 1. Preparation of injection

[0067] Weigh 1.5g type II cannabinoid receptor agonist, add 50g PEG-400, dissolve; prepare 50g pH5.5 phosphate buffer, weigh 0.02g sodium bisulfite and add to the above phosphate buffer; add the buffer Into the PEG solution, mix well, add 0.01% activated carbon for needles and keep warm at 100°C for 30 minutes, filter through a G3 vertically fused glass funnel, and filter through a 0.22 μm microporous membrane. The subpackaged injection can be directly pressed into a stopper or pressed into an aluminum cap to form an injection.

[0068] 2. Preparation of freeze-...

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Abstract

The invention relates to the field of cerebral hemorrhage drugs, in particular to the application of type II cannabinoid receptor agonists in the preparation of drugs for the recovery of neurological function and brain atrophy after hypertensive cerebral hemorrhage. The invention provides the application of a type II cannabinoid receptor agonist in the preparation of a drug for the recovery of neurological function and cerebral edema after hypertensive cerebral hemorrhage. The present invention finds through in vivo experiments that the type II cannabinoid receptor agonist can reduce the degree of brain tissue edema induced by autologous blood and prevent brain atrophy; the use of the drug after hypertensive cerebral hemorrhage can significantly improve neurological function recovery. In addition, the type II cannabinoid receptor agonist is used in combination with minocycline, and the minocycline can significantly increase the blood-brain barrier penetration rate of the type II cannabinoid receptor agonist, and increase the therapeutic effect of anti-inflammatory effect.

Description

technical field [0001] The invention relates to the field of cerebral hemorrhage drugs, in particular to the application of type II cannabinoid receptor agonists in the preparation of drugs for the recovery of neurological function and cerebral edema after hypertensive cerebral hemorrhage. Background technique [0002] Hypertensive intracerebral hemorrhage is one of the most serious complications of hypertension. It often occurs between 50 and 70 years old. It is often caused by rupture and hemorrhage of lenticular artery in the basal ganglia area, accompanied by neurological sequelae such as severe brain atrophy and neurological dysfunction. In addition to surgical removal of hematoma, cerebrospinal fluid drainage and other surgical methods, drugs are the main means to improve the sequelae of hypertensive cerebral hemorrhage. At present, there is no effective drug treatment clinically. [0003] Type II cannabinoid receptor (Cannabinoid Receptor2, CB2R) is one of the main r...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/352A61K31/65A61P9/00A61P25/00A61P25/28
CPCA61K45/06A61K9/0019A61K9/08A61K9/19A61K9/2059A61K9/4866A61K31/352A61K31/65A61K47/02
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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