Preventives and remedies for complications of diabetes

A therapeutic agent and technology for diabetes, applied in the field of prevention and treatment of diabetic complications, can solve the problem of unknown expression of osteopontin and the like

Inactive Publication Date: 2004-01-21
NISSAN CHEM IND LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of osteopontin expression is unknown

Method used

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  • Preventives and remedies for complications of diabetes
  • Preventives and remedies for complications of diabetes
  • Preventives and remedies for complications of diabetes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Inhibition of Kidney and Vascular Osteopontin mRNA Expression in Diabetic Rats Induced by Streptozotocin (STZ)

[0026] The effect of pitavastatin calcium on the expression of osteopontin mRNA in the kidneys and blood vessels of streptozotocin (STZ)-induced diabetic rats was determined by the following method.

[0027] That is, for Wistar rats (body weight: about 300 g), 35 mg of STZ dissolved in physiological saline at a concentration of 50 mg / mL was injected per 1 kg of body weight through the tail vein, and about 1 hour later, 1 mL (3 mg / mL) per 1 kg of body weight was injected using a gastric probe. / kg) A 0.5% carboxymethylcellulose solution (3 mg / kg) of the drug to be tested (pitavastatin calcium) was forcibly orally administered. Then, the same amount of medicine was compulsorily orally administered once a day. In the control group, only the same amount of 0.5% carboxymethylcellulose solution was forcibly orally administered. On the second day of the...

Embodiment 2

[0039] Example 2: Inhibition of Osteopontin Protein Secretion in Rat Aortic Smooth Muscle Cells

[0040] The effect of pitavastatin calcium and atorvastatin on the protein secretion of osteopontin in the culture supernatant of rat aortic smooth muscle cells cultured at normal glucose concentration was measured by the following method.

[0041] First, rat aortic smooth muscle cells (subcultured for 5 to 10 passages) were planted on a 6-well culture dish, and Eagle's Dulbecco's modified with low glucose (1000 mg / L) containing 10% fetal bovine serum (FBS: manufactured by BioWhittaker) was used. The culture medium (DMEM) was cultured confluently under the atmosphere of 5% CO2 and 37°C. Then, it was replaced with the same medium to which the test drugs (pitavastatin calcium and atorvastatin) were added, and cultured for 48 hours. Each well was replaced with 1.5 mL of the same medium not containing FBS, cultured for an additional 48 hours, and the supernatant was recovered. Add an...

Embodiment 3

[0047] Example 3: Effects of Mevalonate on Osteopontin mRNA Expression and Osteopontin Protein Secretion Inhibition of Rat Aortic Smooth Muscle Cells

[0048] The effect of mevalonate on pitavastatin calcium inhibiting the expression of osteopontin mRNA in rat aortic smooth muscle cells cultured at normal glucose concentrations and the protein secretion of osteopontin protein in the culture supernatant, using the following Method determination.

[0049] Rat aortic smooth muscle cells (subcultured for 5 to 10 generations) were planted on 6-well culture dishes, and treated with low glucose (1000 mg / L) DMEM containing 10% FBS in 5% CO 2 , Confluent culture at 37°C. Then, it was replaced with the same medium supplemented with pitavastatin calcium (8 μM) and / or mevalonate (100 μM), and cultured for 48 hours. Each well was replaced with 1.5 mL of the same medium not containing FBS, and cultured for another 48 hours.

[0050] After culturing, the cells attached to the culture dish...

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PUM

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Abstract

The present invention relates to the pharmaceutical useful for the prevention and the treatment of diabetic complications such as diabetic nephropathy, diabetic neuropathy, diabetic retinopathy and diabetic angiopathy among others, and to the prophylaxis and / or treatment drug for diabetic complications with the compound shown in the formula (1) <CHEM> (wherein R is organic group, X is -CH2CH2- or -CH=CH-, and M is hydrogen atom, C1-10 alkyl group or physiologically acceptable cation group) or its lactonized form as the active ingredient.

Description

technical field [0001] The present invention relates to a preventive and therapeutic agent for diabetic complications, which contains a compound having 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitory activity as an active ingredient. In particular, it relates to agents for the prevention and treatment of the onset and progression of diabetic nephropathy, diabetic neurosis, diabetic retinopathy and diabetic vascular disorders. Background technique [0002] It is known that diabetes is accompanied by complications such as diabetic nephropathy, diabetic neurosis, diabetic retinopathy or diabetic vascular disorder, and strict blood sugar control must be carried out in its prevention and treatment. Among these comorbidities, tissue fibrosis or calcification is found. In the state of hyperglycemia, either produce glycosylated protein as a regulator of cell function, or activate intracellular polyol channels to accumulate sorbitol, activate intracellular protease (PK...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/191A61K31/192A61K31/22A61K31/25A61K31/40A61K31/405A61K31/47A61K31/505A61P3/10A61P9/00A61P13/12A61P25/00A61P27/02A61P43/00C07D215/14
CPCA61K31/47A61K31/192A61K31/25A61K31/505A61K31/405A61K31/191C07D215/14A61K31/22A61K31/40A61P13/12A61P25/00A61P25/02A61P27/02A61P27/12A61P3/10A61P43/00A61P9/00
Inventor 北原真树斋藤康森圣二郎竹本稔玉木太郎
Owner NISSAN CHEM IND LTD
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