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Application of compound P57 or analogs thereof to body temperature reduction and neuroprotection

A technology of compounds and analogs, applied in the fields of steroids, neurological diseases, chemical instruments and methods, etc., which can solve the problems of limited patients and limited time window, etc.

Pending Publication Date: 2022-02-22
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite the high prevalence, the number of patients who can receive intervention is limited due to the limited time window

Method used

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  • Application of compound P57 or analogs thereof to body temperature reduction and neuroprotection
  • Application of compound P57 or analogs thereof to body temperature reduction and neuroprotection
  • Application of compound P57 or analogs thereof to body temperature reduction and neuroprotection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Embodiment 1, P57 induces hypothermia in mice and rats

[0053] 1.1 Materials

[0054] 1.1.1 C57BL / 6J 6-8 week old male mice

[0055] 1.1.2 Wistar male rats aged 6-8 weeks

[0056] 1.1.3 Dimethylsulfoxide (DMSO)

[0057] 1.1.4 Castor oil

[0058] 1.1.5 Phosphate buffer solution (PBS)

[0059] 1.1.6 75% ethanol solution

[0060] 1.1.7 Lincomycin lidocaine gel

[0061] 1.1.8 Povidone-iodine solution

[0062] 1.1.9 Double tube micro-dosing system for mice

[0063] 1.1.10 1mL disposable sterile syringe

[0064] 1.1.11 5μL Microsyringe

[0065] 1.1.12 1.5mL EP tube

[0066] 1.1.13 15mL centrifuge tube

[0067] 1.2 Equipment

[0068] 1.2.1 Mouse rectal temperature detector

[0069] 1.2.2 Desktop digital stereotaxic instrument

[0070] 1.2.3 Mouse Adapter

[0071] 1.2.4 Mini Round Head Electric Drill

[0072] 1.3 Solution

[0073] 1.3.1 P57 was dissolved in 1% DMSO + 9% castor oil + 90% PBS solution.

[0074] 1.3.2 Preparation of 5% water and chloral solution...

Embodiment 2

[0086] Example 2 The neuroprotective effect of P57 in the treatment of hypoxic-ischemic diseases

[0087] 2.1 Materials

[0088] 2.1.1 2,3,5-Triphenyltetrazolium Chloride

[0089] 2.1.2 Nylon monofilament suture

[0090] 2.2 Equipment

[0091] 2.2.1 Ventilator

[0092] 2.2.2 Vevo 2100 Micro Ultrasound System

[0093] 2.3 Solution

[0094] 2.3.1 Preparation of 1% 2,3,5-triphenyltetrazolium chloride (2,3,5-triphenyltetrazolium chloride, TTC) solution: Weigh 1 g of TTC and dissolve it in 100 mL of 1×PBS solution.

[0095]2.3.2 Preparation of 4% paraformaldehyde solution: Dissolve 4g of paraformaldehyde in 1×PBS solution, adjust the pH to 7.4, dilute to 100mL, and filter. Protect from light and store at 4°C for later use.

[0096] 2.4 Method

[0097] 2.4.1 Establishment of rat middle cerebral artery occlusion (MCAO) animal model

[0098] Rats of Wistar strain were randomly divided into sham operation blank control group, sham operation drug intervention group, MCAO blank ...

Embodiment 3

[0110] Example 3 Effect of P57 on treating fever

[0111] 3.1 Materials

[0112] 3.1.1 Prostaglandin E2 (PGE2)

[0113] 3.2 Solution

[0114] 3.1.1 PGE2 solution: Dissolve PGE2 to 2M in normal saline.

[0115] 3.3 Method:

[0116] fever model

[0117] The mice implanted with the micro-dosage system two weeks ago and in good health were randomly divided into blank control group, P57 group, PGE2 group, and P57+PGE2 group. Weigh and record the body weight of the mice. One hour before the drug treatment, the body temperature of the mice was recorded by the metabolic cage, P57 (25 mg / kg) was injected intraperitoneally in the P57 group and the P57+PGE2 group, and the other groups were injected with solvent; 1 hour later, the hypothalamus of the PEG2 group and the P57+PGE2 group was injected PGE2 (2μL), and the other groups were injected with solvent.

[0118] 3.4 Results

[0119] In the MCAO model, we found that the body temperature of rats in the control group was higher th...

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PUM

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Abstract

The invention provides an application of a compound P57 or analogues thereof to body temperature reduction and neuroprotection. Specifically, the invention particularly provides application of a compound shown as a formula I to preparation of a pharmaceutical composition for reducing the body temperature of a treated object. The compound can be used for neuroprotection of hypoxic ischemic diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the neuroprotective effect of P57 and its analogs in lowering body temperature and treating hypoxic-ischemic diseases and the application in fever. Background technique [0002] Natural products are derived from animals, plants, microorganisms and other individuals or chemical components from these organisms, mainly including flavonoids, anthraquinones, saponins, alkaloids, terpenes, polypeptides, polysaccharides and proteins and other types. Natural products, especially medicinal plants, are still an important source of new chemical entities (NCES) drugs. [0003] Physical hypothermia has been used as a first-aid measure for many acute hemorrhagic diseases, but the rapid and specific induction of hypothermia by small molecules has not yet been applied clinically. Hibernation is a stress protection measure for living organisms to deal with extreme cold, and loweri...

Claims

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Application Information

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IPC IPC(8): C07J17/00A61K31/704A61P9/10A61P25/00A61P9/00A61P29/00
CPCC07J17/005A61P9/10A61P25/00A61P9/00A61P29/00
Inventor 俞飚党永军裴成锋王瑞娜张夏衡蒋维马君君李增霞陈小平刘超马玉勇徐鹏
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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