Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Novel prophylactic and/or therapeutic agent for diabetic neuropathy

Inactive Publication Date: 2010-02-10
ASTELLAS PHARMA INC
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report on the effectiveness of morpholine derivatives (including Indeloxazine) on diabetic neurological disorders

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Novel prophylactic and/or therapeutic agent for diabetic neuropathy
  • Novel prophylactic and/or therapeutic agent for diabetic neuropathy
  • Novel prophylactic and/or therapeutic agent for diabetic neuropathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] STZ (streptozotocin) induced diabetic rats were prepared by the following steps. At 7 weeks of age, STZ (45 mg / kg) was administered intravenously. In the second week after STZ administration, blood was collected from the tail vein and the blood glucose level was measured, and it was found that the blood glucose level had increased by more than 300 mg / dL. According to the weight, blood sugar level, and the average value of the pain response threshold measured the day before the administration, the administration groups are divided into groups so that the deviation of each group is small. Separately prepare the non-administered STZ group as the normal group. The test drug was administered orally once a day for 28 consecutive days. According to the Von Frey Test (Pain Threshold Test), sensory abnormalities caused by neurological disorders were measured at two time points, one hour after the end of the administration on the 28th day and the 7th day after the end of the adm...

Embodiment 2

[0092] In order to verify whether (+)-2-[(inden-7-yloxy)methyl]morpholine·hydrochloride can cure the neurological disorder itself, we studied (+)-2-[ in STZ-induced diabetic rats (Indene-7-yloxy)methyl]morpholine hydrochloride improves motor nerve conduction velocity (MNCV). The method of Cameron et al. (The Journal of Experimental Physisology 1989, Vol. 74, p917-926) was partially modified to perform this measurement.

[0093] The animals used in the measurement were the rats in the solvent administration group in Example 2 and the 30 mg / kg administration group on the 7th or 8th day after the continuous administration was terminated, respectively. In addition, the same test was performed on the normal group. Rats were anesthetized with phenobarbital sodium, and the rectal temperature was maintained at 37.5°C in a body temperature maintaining device for small animals, and MNCV was measured using an evoked potential measuring device. First, install stimulating positive electrode...

Embodiment 3

[0105] In order to verify whether (+)-2-[(inden-7-yloxy)methyl]morpholine·hydrochloride acts on the expression of neurotrophic factors, we studied (+)-2-[(inden-7- (Oxyoxy)methyl]morpholine·hydrochloride improves the expression of neurotrophic factors in the spinal cord and heel nerve nodes of STZ-induced diabetic rats.

[0106] The neuronutrition of the animals on the 7th or 8th day after the end of continuous administration was measured in the normal group, the vehicle administration group of STZ-induced diabetic rats, and the 30mg / kg administration group in Example 2 respectively. Factor expression. The lumbar spinal cord and heel ganglia (L4, L5, L6) were extracted, and total RNA was extracted using RNA extraction kit RNeasy (Qiagen). The extracted RNA is used as a template for in vitro reverse transcription reaction to obtain cDNA. Adopted for fibroblast growth factor 2 (FGF-2), insulin-like growth factor 1 (IGF-1) and glyceraldehyde 3-phosphate dehydrogenase (Glyceraldehy...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Disclosed is an excellent prophylactic and / or therapeutic agent for diabetic neuropathy, which comprises a 2-¢(substituted-indene-7-yloxy)methyl!morpholine represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient. The prophylactic and / or therapeutic agent is particularly useful as a prophylactic and / or therapeutic agent for diabetic motor nerve disorder(e.g., decrease in muscular strength (decrease in muscular strength to an extent of being unable to independently walk)), diabetic sensory nerve disorder (paresthetic (abnormal vibratory sensation), allodynia, reduced sensation (numbness in limbs, psychroesthesia) or pain), or diabetic autonomic nerve disorder (e.g., abnormal bowel habituation such as constipation and diarrhea, urinary dysfunction, impotence, orthostatic hypotension, dyshidrosis, abnormal heart rate variability, delayed gastric emptying). Also disclosed is an ameliorating gent for a disease condition of diabetic nerve disorder.

Description

Technical field [0001] The present invention relates to a novel medical application of a morpholine derivative or a pharmaceutically acceptable salt thereof as a preventive and / or therapeutic agent for diabetic neurological disorders. Background technique [0002] Diabetic complications are known to include three major complications: retinopathy (eyes), neurological disorders (nerves) and nephropathy (kidneys), which have become a major clinical problem. [0003] According to Thomas et al. (Diabetes 1997, Volume 46, Suppl.2, pS54-S57), diabetic neurological disorders include multiple neurological disorders and single neurological disorders, and multiple disorders include sensory nerves, which are the peripheral nervous system, Motor nerve and autonomic nerve disorders. In diabetic sensory nerve disorders, acute symptoms include numbness, pain and other paresthesias; chronic symptoms include hypoesthesia (numbness of limbs, vibration sensation, cold and warm sensation, etc.), pain,...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D265/30A61K31/5375A61P3/10A61P25/04
CPCA61K31/5375A61P25/00A61P25/02A61P25/04A61P29/00A61P3/10
Inventor 青木俊明村井信仁田村诚司山本博子浜川望
Owner ASTELLAS PHARMA INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com