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Agent for inhibiting thickening of peritoneal membrane

A peritoneal hypertrophy and inhibitor technology, applied in the field of peritoneal hypertrophy inhibitor, can solve problems such as abnormal blood vessels, achieve the effects of strong lipid affinity, reduced drug side effects, and easy operation and use

Active Publication Date: 2015-03-18
CCI HLDG INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, in patients undergoing peritoneal dialysis treatment, the well-known peritoneal hypertrophy disorders such as cystic peritoneal sclerosis (EPS), peritoneal sclerosis, or peritoneal fibrosis can develop
Although the cause of peritoneal hypertrophy has not yet been fully clarified, the following phenomena have been found, such as abnormal blood vessels and increased number of blood vessels in hypertrophic peritoneal tissue as shown in Non-Patent Document 1, and intraperitoneal hypertrophy of patients undergoing peritoneal dialysis. There is a higher concentration of vascular endothelial growth factor (VEGF) in the fluid, so it is inferred that there is a close relationship between angiogenesis and peritoneal hypertrophy

Method used

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  • Agent for inhibiting thickening of peritoneal membrane
  • Agent for inhibiting thickening of peritoneal membrane
  • Agent for inhibiting thickening of peritoneal membrane

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0106]

[0107] Intraperitoneal delivery of chlorhexidine in mice (C57 / BL6, 7 weeks postnatal male, weighing 21±1 g) produced a model of peritoneal hypertrophy (Junor BJR, Briggs JD, Forwell MA, Dobbie JW, Henderson I: Sclerosing peritonitis - The cotribution of chlorhexidine in alcohol. Perit Dial Bull 101-104, 1985). Specifically, the mice were divided into three groups: CG group (5 rats), control group (4 rats), and TMG group (5 rats). Do the following for each group.

[0108] (CG group)

[0109] 0.2 mL of a solution of 0.1% chlorhexidine / 15% ethanol / physiological saline was intraperitoneally delivered to the mice three times a week.

[0110] (control group)

[0111] 0.2 mL of a 15% ethanol / physiological saline solution was intraperitoneally delivered to the mice three times a week.

[0112] (TMG group)

[0113] In a solution of 0.1% chlorhexidine / 15% ethanol / physiological saline, add TMG (=2-(α-D-glucopyranosyl)methyl-2,5,7,8- Tetramethylchroman-6-ol for short) int...

Embodiment 2

[0119]

[0120] The result after H.E staining is carried out to the peritoneal tissue section that makes in embodiment 1, as Figure 1-A , Figure 1-B , Figure 1-C shown. In addition, the thickness of the peritoneum was measured, and each mouse was randomly measured at 10 locations, and then the average value was calculated. The results are shown in Table 1.

[0121] [Table 1]

[0122]

Peritoneal thickness (μm)

[0123] CG group

82.3±24.5

refer to Figure 1-A

TMG group

42.1±19.7 a

refer to Figure 1-B

control group

9.1±2.8 b

refer to Figure 1-C

[0124] a Pb P<0.0001 versus CG(t test)

[0125] from Figure 1-A~Figure 1-C From the results in Table 1, it became clear that the peritoneal hypertrophy phenomenon caused by CG delivery was effectively suppressed in the TMG delivery group.

Embodiment 3

[0127]

[0128] The peritoneal tissue sections prepared in Example 1 were immunostained using the polyclonal antibody RABBIT ANTI MOUSE COLLAGEN I (polyclonal IgG) (AbD Serotec; UK) against type I collagen, and the results were as follows: Figure 2-A , Figure 2-B , Figure 2-C shown. Antibody activation was performed in an autoclave, and immunostaining was performed using antibodies diluted 250-fold. Under the condition of 400 times magnification of the field of view, the proportion of type I collagen targeting the peritoneum on the wall side of each mouse was measured, and 10 parts were randomly measured during the measurement, and then the average value was calculated. The results are shown in Table 2.

[0129] [Table 2]

[0130]

Type I collagen occupied area (%)

CG group

18.55±2.06

refer to Figure 2-A

TMG group

8.68±1.85 a

refer to Figure 2-B

control group

1.94±0.46 b

refer to Figure 2-C

...

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Abstract

Disclosed are: a thickening-inhibiting agent for inhibiting thickening of the peritoneal membrane by which thickening of the peritoneal membrane can be inhibited, prevented or treated with relieved side effects; and a dialysis solution which contains this thickening-inhibiting agent. Specifically disclosed are: an agent for inhibiting thickening of the peritoneal membrane, which contains, as the active ingredient, a chromanol glycoside represented by chemical formula (1); and a dialysis solution containing the same. In chemical formula (1), R 1 , R 2 , R 3 and R 4 are either the same or different and each represents a hydrogen atom or a lower alkyl group; R 3 represents a hydrogen atom, a lower alkyl group or a lower acyl group; X represents a monosaccharide residue or an oligosaccharide residue, in which the hydrogen atom in a hydroxyl group in each saccharide residue may be substituted by a lower alkyl group or a lower acyl group; n is an integer of 0 to 6; and m is an integer of 1 to 6.

Description

【Technical field】 [0001] The present invention relates to a peritoneal hypertrophy inhibitor for inhibiting peritoneal hypertrophy. 【Background technique】 [0002] At present, there are about 220,000 patients receiving artificial dialysis in Japan due to symptoms of renal failure with decreased or impaired renal function. About 95% of the patients received hemodialysis using an extracorporeal circulation circuit, and the remaining 5% received peritoneal dialysis. When hemodialysis is used for treatment, patients are generally required to go to a specialized hospital about 3 times a week (one time takes about 4 hours) to drain blood outside the body and remove metabolic waste, so it is easy to be limited by time. On the other hand, peritoneal dialysis means that a dialysate catheter is embedded in the abdomen, and a dialysate with a high osmotic pressure is introduced into the peritoneal cavity covered by the peritoneum (covering internal organs such as the stomach and intes...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H15/26A61K31/7048A61K47/26A61M1/14A61P1/00A61P7/08
CPCA61K9/0019A61K31/7048A61M1/28C07H15/26A61M1/287A61P1/00A61P7/08
Inventor 村瀬博宣友雅司
Owner CCI HLDG INC