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Prophylactic or therapeutic agent for diseases associated with pains in urinary organs

A technology of prophylactic and therapeutic agents, applied in the directions of urinary system diseases, skeletal diseases, nervous system diseases, etc., can solve the problems of unpublished and concretely showing the effectiveness of treating interstitial cystitis, etc.

Inactive Publication Date: 2013-01-02
ASTELLAS PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, data specifically showing effectiveness in the treatment of interstitial cystitis has not been published

Method used

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  • Prophylactic or therapeutic agent for diseases associated with pains in urinary organs
  • Prophylactic or therapeutic agent for diseases associated with pains in urinary organs
  • Prophylactic or therapeutic agent for diseases associated with pains in urinary organs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0094] Screening of substances that inhibit FAAH activity using cells derived from human urothelial carcinoma

[0095] (1) Screening of substances that inhibit FAAH activity

[0096] Using RPMI1640 medium (Invitrogen Company) containing 10% fetal bovine serum (HyClone Company), the cell line 5637 cells (HTB-9; ATCC) derived from human bladder cancer were cultured at 1 × 10 per well. 5 seeded into 48-well cell culture plates. After culturing at 37°C for more than 12 hours, the cells were washed with 400 µl per well of a buffer solution (Hank's Balanced Salt Solution, 20 mM Hepes-NaOH (pH 7.4)). To the substrate solution (containing 3 μCi / ml radiolabeled anandamide [ethanolamine 1- 3 H]) and the above-mentioned buffer solution of 10 μM anandamide) were added with the test substance dissolved in DMSO so as to be 0.003 nM to 30 nM. As a control, only DMSO was added. Add 100 μl of substrate solution per well to the above cells, and in CO 2 Incubate at 37°C for 30 minutes in an...

Embodiment 2

[0102] Effects of compounds on rats with frequent urination induced by cyclophosphamide (CPA)

[0103]The effect of compounds on improving symptoms of bladder irritation was studied using a pathological model. Cyclophosphamide (CPA) is known to damage the bladder mucosa from urine through systemic administration to the metabolite acrolein. In rats, bladder pain and frequent urination accompanying hemorrhagic cystitis were induced by administration of CPA, and thus the drug effect on these symptoms could be evaluated. In the experiment, 9-week-old Wistar female rats (Nippon Chalus Riber Co., Ltd.) were used. CPA (100 mg / kg) was administered intraperitoneally, and the experiment was performed two days later. The test compound was orally administered using 0.5% methylcellulose as a solvent, and 15 minutes later, distilled water (30 ml / kg) was compulsorily orally administered. Rats were placed in metabolic cages, and the urine weight was continuously measured for one hour. Eff...

Embodiment 3

[0105] Effects of Compounds on Bladder Pain Model Rats

[0106] The analgesic effect of compounds on bladder pain was studied using a pathological model. Cyclophosphamide (150 mg / kg) was administered intraperitoneally, and two days later, the bladder was rapidly distended by injecting physiological saline at a flow rate of 45 ml / hour through a catheter inserted through the urethra into the bladder under unrestrained conditions. Spike enhancement of the external oblique muscle EMG with pain-related behaviors was observed by rapidly distending the bladder. The injection amount at this time can be regarded as the bladder pain threshold, and thus the drug effect on the bladder pain threshold can be evaluated. In the experiment, 7-week-old female SD rats (Nippon Chalus River Co., Ltd.) (n=3-6) were used. For rats pretreated with cyclophosphamide, the bladder pain threshold was measured before and after administration of the test compound, and the amount of change (Δml) was examin...

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Abstract

Disclosed is a prophylactic or therapeutic agent for diseases associated with pains in urinary organs. It is confirmed that a pyridyl non-aromatic nitrogenated heterocyclic-1-carboxylate compound or a salt thereof has an effective bladder capacity increasing activity and also has an analgesic activity on pains in the bladder and the testis, which rely on a FAAH inhibiting activity thereof. Therefore, a pyridyl non-aromatic nitrogenated heterocyclic-1-carboxylate compound or a salt thereof can be used for the prevention or treatment of interstitial cystitis / bladder pain syndrome and / or chronic non-bacterial prostatitis / chronic pelvic pain syndrome.

Description

technical field [0001] The present invention relates to a preventive or therapeutic agent for diseases accompanied by urinary organ pain such as interstitial cystitis / bladder pain syndrome and chronic nonbacterial prostatitis / chronic pelvic pain syndrome. Background technique [0002] Both interstitial cystitis / bladder pain syndrome and chronic nonbacterial prostatitis / chronic pelvic pain syndrome are diseases in which frequent urination and bladder pain are one of the main symptoms (Neurourology and Urodynamics, Vol. 21, pp. 167-178 pp. 2002; The Journal of Urology, Vol. 168, pp. 593-598, 2002). [0003] Interstitial cystitis (interstitial cystitis) is a non-infectious cystitis that is more common in women aged 20 to 60. It is a disease with suprapubic pain, frequent urination, and urgency to urinate as the main symptoms. However, there are no common diagnostic criteria and definitive treatment methods. In 1987, the National Institute of Diabetic, Digestive and Kidney Dis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4545A61K31/496A61P13/00A61P13/08A61P13/10A61P19/00A61P25/04A61P29/00A61P43/00C07D213/65C07D213/80C07D401/12C07D401/14C07D413/14
CPCC07D401/14C07D401/12C07D413/14A61K31/4545A61K31/496C07D213/80C07D213/65A61P13/00A61P13/08A61P13/10A61P19/00A61P25/04A61P29/00A61P31/04A61P43/00
Inventor 染谷晃好林田纮子甲田舞棚桥正幸吉冈克郎
Owner ASTELLAS PHARMA INC
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