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Novel medicinal application of carboxyl aminotriazole and acceptable salts of the carboxyl aminotriazole

A technology of carboxytriazole and its use, which is applied in the field of new medical applications of carboxyamidotriazole and its available salts, and can solve the problems of few specific therapeutic drugs

Active Publication Date: 2010-01-06
GUANGDONG YINZHU PHARMACEUTICAL TECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In clinical treatment, except for hormones, immunosuppressants, and aminosalicylic acid preparations, there are few specific therapeutic drugs

Method used

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  • Novel medicinal application of carboxyl aminotriazole and acceptable salts of the carboxyl aminotriazole
  • Novel medicinal application of carboxyl aminotriazole and acceptable salts of the carboxyl aminotriazole
  • Novel medicinal application of carboxyl aminotriazole and acceptable salts of the carboxyl aminotriazole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Example 1: The protective effect of drugs on ALS transgenic model animals

[0075] B6SJL-Tg(SOD1*G93A)1Gur / J transgenic mice, which overexpress the human SOD1 gene containing mutations identified in ALS patients, develop adult-onset, progressive animal degeneration. These transgenic mice are considered a model of the disease and have been used to test a number of strategies to delay disease progression and mortality.

[0076] In order to evaluate the potential benefits of the present invention to ALS, the SOD1G93A transgenic mice of the control group and the administration group were orally administered with PEG400 solvent, CAI or various analogs of CAI (the compound of the structural formula is A, wherein R 1 is Cl or H, R 2 For Cl, H, Br, CH 3 , or CF 3 , R 3 Cl, Br, CF 3 , NO 2 or CN, X is O, S, or C=O). The four carboxyaminotriazole analogues used in this example are A1-A4 in Table 1, respectively, and the doses are all 20 mg / kg. Dosing began when mice were ...

Embodiment 2

[0082] Example 2: Carboxytriazole inhibits MPTP-induced oxidative stress

[0083] Male C57BL / 6 mice, weighing 18g-22g, 12 / group, were divided into 4 groups. Animals were given carboxytriazole by intragastric administration every day for 8 consecutive weeks, the doses were 0, 10, 20, or 40 mg / kg / day. On the day of the study, mice were subcutaneously injected with 30 mg / kg of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to increase oxidative stress in the animals' brains. irritating reaction. One hour later, the mice were intraperitoneally injected with 100 mg / kg of sodium salicylate. One hour after the injection, the animals were sacrificed, the forebrain was separated, and the content of 2,3-dihydroxybenzoic acid (2,3-DHBA) was determined.

[0084] Such as image 3 As shown, the results show that treatment with carboxytriazole at doses of 20 and 40 mg / kg / day can significantly reduce the forebrain oxidative stress produced by MPTP, thereby inhibiting n...

Embodiment 3

[0085] Example 3: Carboxytriazole analogues inhibit MPTP-induced oxidative stress

[0086] Male C57BL / 6 mice, body weight 18g-22g, 10 mice / group, divided into 11 groups. The animals were given the compounds A1-A10 in Table 1 by intragastric administration every day for 8 consecutive weeks, and the dose was 20 mg / kg / day. On the day of the study, mice were subcutaneously injected with 30 mg / kg of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to increase oxidative stress in the animals' brains. irritating reaction. One hour later, the mice were intraperitoneally injected with 100 mg / kg of sodium salicylate. One hour after the injection, the animals were sacrificed, the forebrain was separated, and the content of 2,3-dihydroxybenzoic acid (2,3-DHBA) was determined.

[0087] Such as Figure 4 As shown, the results showed that carboxylaminotriazole analogues such as A1-A10 could reduce the forebrain oxidative stress produced by MPTP to varying degrees, there...

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Abstract

The invention discloses application of carboxyl aminotriazole or pharmaceutically acceptable salts of the carboxyl aminotriazole in the preparation of medicaments for preventing and / or treating neurodegenerative diseases, amyotrophic lateral sclerosis and inflammatory bowel diseases and also relates to the medicament packages or kits comprising the medicaments.

Description

technical field [0001] The present invention relates to the new medicine use of carboxyamidotriazole (carboxyamidotriazole, CAI) or its pharmaceutically acceptable salt, analogue or derivative, especially its preparation prevention or treatment neurodegenerative disease and / or inflammatory bowel disease application in medicine. More specifically, the present invention relates to compositions comprising carboxyamidotriazole or pharmaceutically acceptable salts, derivatives, analogs thereof and the use of such compositions for the prevention or treatment of amyotrophic lateral sclerosis and / or inflammatory Uses for intestinal disorders. technical background [0002] Amyotrophic lateral sclerosis (ALS) is a progressive fatal motor neuron disease (motor neuron disease, MND), also known as Lou Gehrig's disease, the anterior horn of the spinal cord and brainstem motor neurons As well as chronic progressive degeneration of the pyramidal tract, characterized by simultaneous damage...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4192A61P25/28A61P25/16A61P25/00A61P1/00
Inventor 张德昌叶菜英郭磊郝晓键郑茹
Owner GUANGDONG YINZHU PHARMACEUTICAL TECHNOLOGY CO LTD
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