JPH0577656B2 - - Google Patents
Info
- Publication number
- JPH0577656B2 JPH0577656B2 JP91305565A JP30556591A JPH0577656B2 JP H0577656 B2 JPH0577656 B2 JP H0577656B2 JP 91305565 A JP91305565 A JP 91305565A JP 30556591 A JP30556591 A JP 30556591A JP H0577656 B2 JPH0577656 B2 JP H0577656B2
- Authority
- JP
- Japan
- Prior art keywords
- kallidinogenase
- peripheral vascular
- therapeutic agent
- external
- test
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 102000001399 Kallikrein Human genes 0.000 claims description 46
- 108060005987 Kallikrein Proteins 0.000 claims description 46
- 229960003709 kallidinogenase Drugs 0.000 claims description 46
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 17
- 229940124597 therapeutic agent Drugs 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000002674 ointment Substances 0.000 claims description 5
- 239000006071 cream Substances 0.000 claims description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 4
- 239000001509 sodium citrate Substances 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 238000012360 testing method Methods 0.000 description 16
- 230000000694 effects Effects 0.000 description 13
- 238000010521 absorption reaction Methods 0.000 description 11
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000000006 Nitroglycerin Substances 0.000 description 7
- 229960003711 glyceryl trinitrate Drugs 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 210000002700 urine Anatomy 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical group C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- -1 Polyethylene Polymers 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 108010051594 prolyl-phenylalanyl-arginine naphthylester Proteins 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 229940099259 vaseline Drugs 0.000 description 2
- OMRXVBREYFZQHU-UHFFFAOYSA-N 2,4-dichloro-1,3,5-triazine Chemical compound ClC1=NC=NC(Cl)=N1 OMRXVBREYFZQHU-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYSKZKQBTVLYEQ-FSLKYBNLSA-N Kallidin Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)CCC1 FYSKZKQBTVLYEQ-FSLKYBNLSA-N 0.000 description 1
- 108010003195 Kallidin Proteins 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 102000010631 Kininogens Human genes 0.000 description 1
- 108010077861 Kininogens Proteins 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000270666 Testudines Species 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000000987 azo dye Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008269 hand cream Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- IYCJIJCQIVJOKW-SDHOMARFSA-N naphthalen-1-yl (2s)-5-(diaminomethylideneamino)-2-[[(2s)-3-phenyl-2-[[(2s)-pyrrolidine-2-carbonyl]amino]propanoyl]amino]pentanoate Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)OC=1C2=CC=CC=C2C=CC=1)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 IYCJIJCQIVJOKW-SDHOMARFSA-N 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- 229940082004 sodium laurate Drugs 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 208000037997 venous disease Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3305565A JPH0570368A (ja) | 1984-03-23 | 1991-10-25 | 末梢血管障害治療剤 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59054542A JPS60199827A (ja) | 1984-03-23 | 1984-03-23 | 人尿性カリジノゲナーゼを有効成分とする脳代謝障害改善剤 |
| JP3305565A JPH0570368A (ja) | 1984-03-23 | 1991-10-25 | 末梢血管障害治療剤 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59054542A Division JPS60199827A (ja) | 1984-03-23 | 1984-03-23 | 人尿性カリジノゲナーゼを有効成分とする脳代謝障害改善剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0570368A JPH0570368A (ja) | 1993-03-23 |
| JPH0577656B2 true JPH0577656B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-10-27 |
Family
ID=26395305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3305565A Granted JPH0570368A (ja) | 1984-03-23 | 1991-10-25 | 末梢血管障害治療剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0570368A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) |
-
1991
- 1991-10-25 JP JP3305565A patent/JPH0570368A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0570368A (ja) | 1993-03-23 |
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