JPH0434971B2 - - Google Patents
Info
- Publication number
- JPH0434971B2 JPH0434971B2 JP17839485A JP17839485A JPH0434971B2 JP H0434971 B2 JPH0434971 B2 JP H0434971B2 JP 17839485 A JP17839485 A JP 17839485A JP 17839485 A JP17839485 A JP 17839485A JP H0434971 B2 JPH0434971 B2 JP H0434971B2
- Authority
- JP
- Japan
- Prior art keywords
- weight
- indomethacin
- cellulose
- purified water
- add
- 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
Links
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 47
- 229960000905 indomethacin Drugs 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- 239000002674 ointment Substances 0.000 claims description 37
- 238000010521 absorption reaction Methods 0.000 claims description 15
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 14
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 10
- 230000000202 analgesic effect Effects 0.000 claims description 10
- 150000001413 amino acids Chemical class 0.000 claims description 8
- 239000003349 gelling agent Substances 0.000 claims description 8
- -1 furcerelan Polymers 0.000 claims description 7
- 150000003903 lactic acid esters Chemical class 0.000 claims description 7
- 239000002562 thickening agent Substances 0.000 claims description 5
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- 230000001760 anti-analgesic effect Effects 0.000 claims description 4
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 3
- 229920000161 Locust bean gum Polymers 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 235000010418 carrageenan Nutrition 0.000 claims description 3
- 239000000679 carrageenan Substances 0.000 claims description 3
- 229920001525 carrageenan Polymers 0.000 claims description 3
- 229940113118 carrageenan Drugs 0.000 claims description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 235000010420 locust bean gum Nutrition 0.000 claims description 3
- 239000000711 locust bean gum Substances 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 235000010981 methylcellulose Nutrition 0.000 claims description 3
- 229920001059 synthetic polymer Polymers 0.000 claims description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- 239000004472 Lysine Substances 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 2
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 229920005615 natural polymer Polymers 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims 1
- 235000019325 ethyl cellulose Nutrition 0.000 claims 1
- 229920001249 ethyl cellulose Polymers 0.000 claims 1
- 239000008213 purified water Substances 0.000 description 33
- 235000019441 ethanol Nutrition 0.000 description 23
- 238000003756 stirring Methods 0.000 description 21
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 15
- 229940043276 diisopropanolamine Drugs 0.000 description 15
- UKGRTCZMPQERFQ-UHFFFAOYSA-N octadecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)C(C)O UKGRTCZMPQERFQ-UHFFFAOYSA-N 0.000 description 10
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 8
- 229930064664 L-arginine Natural products 0.000 description 8
- 235000014852 L-arginine Nutrition 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 150000002334 glycols Chemical class 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- QQQMUBLXDAFBRH-UHFFFAOYSA-N dodecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)O QQQMUBLXDAFBRH-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 230000003637 steroidlike Effects 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 150000002763 monocarboxylic acids Chemical class 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- GGNDJBOIHAZWMQ-UHFFFAOYSA-N 2-[1-(4-chlorobenzoyl)-2-ethyl-5-methoxyindol-3-yl]acetic acid Chemical compound CCC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 GGNDJBOIHAZWMQ-UHFFFAOYSA-N 0.000 description 1
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000011928 denatured alcohol Substances 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229920003087 methylethyl cellulose Polymers 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- BORJONZPSTVSFP-UHFFFAOYSA-N tetradecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCCCOC(=O)C(C)O BORJONZPSTVSFP-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Description
ïŒç£æ¥äžã®æè¡åéïŒ
æ¬çºæã¯ãæå¹æåãšããŠã€ã³ãã¡ã¿ã·ã³ãå«
æããæ¶çé®çè»èå€ã«é¢ãããã®ã§ããã
ã€ã³ãã¡ã¿ã·ã³ã¯ãïŒâïŒïœâã¯ãããã³ãŸã€
ã«ïŒâïŒâã¡ããã·âïŒâãšãã«ã€ã³ããŒã«âïŒ
âé
¢é
žïŒåååŒïŒC19H16CINO4 ååéïŒ
357.79ïŒã®ååŠåãæããããããéã¹ããã€ã
æ§æ¶çé®çå€ã§ããã
ïŒåŸæ¥ã®æè¡ïŒ
ã€ã³ãã¡ã¿ã·ã³ã¯ãæŽåœ¢å€ç§é åã«ãããŠæ¶ç
é®çã®ç®çã§ãããããéã¹ããã€ãç³»æ¶çé®ç
å€ãåºã䜿çšãããããããèšåºå¹æã確èªãã
ãŠããã
ãããã®è¬å€ã®æäžåœ¢æ
ãšããŠã¯ãã»ãšãã©ã
çµå£å€ã§ãããããäžéšã«éçµå£å€ãšããŠåå€ã®
圢æ
ããšãããŠããã
ããããªãããçµå£å€ã®éã¹ããã€ãç³»æ¶çé®
çå€ã¯ããããªãã®èšåºå¹æãæããäžæ¹ã§ãè
è
žé害çã®å¯äœçšã®é »çºã宿åœçã§ãããšèšãã
ãŠããã
ãã®ããåŸæ¥ããå¯äœçšã®å°ãªãéã¹ããã€ã
ç³»æ¶çé®çå€ã®éçºãçš®ã
è©Šã¿ãããŠããããã
ãŸã ã«ããããæºè¶³ãããã®ã¯åºãŠããªãã
æäžå€åã工倫ããŠå¯äœçšã®è»œæžãå³ãããšã
ç®çãšããŠåå€ã®ç 究ããªãããŠããã
ããããªãããåå€ãçµå£å€ã«æ¯èŒããŠè¥å¹²å¯
äœçšã軜æžããããšã¯ãããäŸç¶ãšããŠæ¶ååšç³»
é害ïŒäŸãã°æªå¿ã»ååã»èžçŒãã»äžç¢ã»è
¹çã»
é£æ¬²äžæ¯ã»é çã»ããŸãçïŒãèŠãããŠããã
åŸã€ãŠåå€ã«ã€ããŠãæ¶ååšç³»é害è
ãžã®æäž
ã«æ
éã«èŠããŠããã
ããã§ããã®ãããªçµå£å€åã³åº§è¬ã®åœ¢æ
ã«ã
ããå¯äœçšãæé€ãã¹ããå±æçã«ã€ã³ãã¡ã¿ã·
ã³ãå¡ã蟌ã¿ãç®èã«åžåããã圢æ
ã®è»èå€ã®
ç 究ããªãããŠããã
ããããªããã€ã³ãã¡ã¿ã·ã³ã¯ãæ°Žåã³éåžžã®
åªäœã«å¯ŸããŠæº¶ãã«ãããšããæ§è³ªãæããŠã
ãã
åŸã€ãŠçŸåšäžè¬ã«äœ¿çšãããŠããè»èãã¯ãªãŒ
ã çã®åºå€ã«æ·»å é
åããŠãã€ã³ãã¡ã¿ã·ã³ã¯åœ
該åºå€äžã«æžæ¿ç¶æ
ã§ååšããŠããã«éãããç®
èããã®åžåæ§ã«åé¡ããããå
åãªæ²»çå¹æã
éæåºæ¥ãªããšãã€ãäžéœåããã€ãã
ãã®æ¬ ç¹ãé€ãããã®ãšããŠæè¿ãã€ã³ãã¡ã¿
ã·ã³ãšãã°ãªã³ãŒã«é¡ãäœçŽã¢ã«ã³ãŒã«åã³æ°Žã
ããªãåªäœãšãã²ã«åå€ãããªãé
åç©ãã²ã«å
ããŠãªãæ¶çé®çè»èå€ïŒç¹å
¬æ56â10886ïŒã
ç¥ãããŠããã
ããããªãããã®æ¶çé®çè»èå€ã¯ãã€ã³ãã¡
ã¿ã·ã³ã®æº¶è§£å€ãšããŠã°ãªã³ãŒã«é¡ïŒäŸãã°ãã
ãã¬ã³ã°ãªã³ãŒã«ãããªãšãã¬ã³ã°ãªã³ãŒã«çïŒ
ãå€é䜿çšããããã«ç®èãžã®åºæ¿æ§ã匷ãïŒã
ã¶ããããïŒãšãã€ãæ¬ ç¹ãæããŠããã
ãŸãã€ã³ãã¡ã¿ã·ã³ã®åžåå©å€ãšããŠC4ãC14
ã®ã¢ãã«ã«ãã³é
žã®C1ãC5ã®ã¢ã«ã³ãŒã«ãšã¹ã
ã«åã³C4ãC10ã®ãžã«ã«ãã³é
žã®C1ãC3ã®ã¢ã«ã³
ãŒã«ãžãšã¹ãã«ïŒäŸãã°ãžã€ãœãããã«ã¢ãžããŒ
ãããžãšãã«ã»ãã±ãŒãçïŒã䜿çšããŠãããåž
åçã¯å
åãªãã®ãšã¯èšããªãã€ãã
ãã®ããç®èãžã®åºæ¿æ§ã匱ããäžã€åžåçã®
é«ãã€ã³ãã¡ã¿ã·ã³ãå«ãè»èå€ãæãŸããŠã
ãã
ïŒçºæã解決ããããšããåé¡ç¹ïŒ
ããã§æ¬çºæã¯ããããåŸæ¥æè¡ã®æ¬ ç¹ã«éã¿
ç®èãžã®åºæ¿ãå°ãªããããã«ç®èãžã®ã€ã³ãã¡
ã¿ã·ã³ã®åžåæ§ã®ããæ¶çé®çè»èå€ãæäŸãã
ããšãç®çãšããã
ïŒåé¡ç¹ã解決ããããã®æ段ïŒ
ããã§æ¬çºæè
éã¯ããããåŸæ¥æè¡ã®å®æ
ã«
éã¿éã¹ããã€ãç³»æ¶çé®çå€ã®å¯äœçšã®è»œæžã
ã¯ãããšãšãã«ãç®èãžã®åºæ¿æ§ã匱ããäžã€åž
åå¹çã®é«ãè»èå€ãæäŸããã¹ãéæç 究ãã
çµæã溶解å€ãšããŠã°ãªã³ãŒã«é¡ã®ä»£ããã«å¡©åº
æ§ã¢ããé
žãçšããã°ç®èãžã®åºæ¿æ§ã匱ããåž
åå©å€ãšããŠC4ãC14ã®ã¢ãã«ã«ãã³é
žã®C1ãC5
ã®ã¢ã«ã³ãŒã«ãšã¹ãã«åã³C4ãC10ã®ãžã«ã«ãã³
é
žã®C1ãC3ã®ã¢ã«ã³ãŒã«ãžãšã¹ãã«ã®ä»£ããã«
ä¹³é
žãšã¹ãã«ãçšããã°åžåå¹çãé«ãããšãèŠ
åºãçºæããã®ã§ããã
å³ã¡æ¬çºæã¯ãã€ã³ãã¡ã¿ã·ã³0.5ã1.5ééïŒ
ãšãå¡©åºæ§ã¢ããé
ž0.3ã10ééïŒ
ãäœçŽã¢ã«ã³
ãŒã«10ã60ééïŒ
ãåã³æ°Ž20ã70ééïŒ
ãããªã
åªäœãšãã²ã«åå€0.2ãïŒééïŒ
ãšä¹³é
žãšã¹ãã«
ãããªã矀ããéžã°ããåžåå©å€0.2ã10ééïŒ
ãšãé
åããŠãªãæ¶çé®çè»èå€ã§ããã
ãããç¡ç
é®çè»èå€ã¯ãåŸæ¥æè¡ã®æ¬ ç¹ãå
æãåŸãæ°èŠãªãçºæã§ãããå®çšäžå€§ããªäŸ¡å€
ãæãããã®ã§ããã
å°æ¬çºæã®æå¹æåã®ã€ã³ãã¡ã¿ã·ã³ã¯ã0.5
ã1.5ééïŒ
ã§å
åã«ãã®å¹æãæåŸ
ããããšã
ã§ããããŸãã€ã³ãã¡ã¿ã·ã³ã®è»èå€ãšããŠã®å
·
åãã¹ãæ¡ä»¶ã¯ã0.5ã1.5ééïŒ
ã®ã€ã³ãã¡ã¿ã·
ã³ã溶解ããæž
涌æãããã䜿çšæãåªããŠã
ããå
åã«è¬å¹ãçºæ®ãããããšã§ãããäžã€ã€
ã³ãã¡ã¿ã·ã³ãååŠçã«å®å®ããŠããããšã§ã
ãã
äžè¬ã«ã€ã³ãã¡ã¿ã·ã³ã®å®å®æ§ã¯ã液æ§ã«å€§ã
ãå·Šå³ããã匷é
žã匷ã¢ã«ã«ãªã§ã¯ããããäžå®
å®ã§ãããæãŸããPHã¯4.5ã6.2ã§ãããšèãã
ãããããããªããã€ã³ãã¡ã¿ã·ã³ã¯ãé
žæ§åŽã«
ãããŠã¯æº¶è§£æ§ãéåžžã«å°ãããçµæ¶æåºãšãã
åé¡ããããå®å®ãªã€ã³ãã¡ã¿ã·ã³è»èãããã
ãšã¯ããããŠå°é£ã§ãã€ãã
ããããªããæ¬çºæã«ãããæ¶çé®çè»èå€
ã¯ãPHã4.5ã6.2ã§ãããªãã極ããŠå®å®ã§ã
ããæ¬çºæã®æº¶è§£å€ãšããŠäœ¿çšããå¡©åºæ§ã¢ãã
é
žãšããŠã¯ããªãžã³ãã¢ã«ã®ãã³ããªã«ããã³ã
ãã¹ããžã³ãªã©ã奜ãŸãããäœãå
åŠæŽ»æ§ã¯ïŒ¬
äœïŒïŒ€äœåã³DLäœãåããªãã
åžåå©å€ãšããŠäœ¿çšããä¹³é
žãšã¹ãã«ãšããŠ
ã¯ãä¹³é
žã©ãŠãªã«ãšã¹ãã«ãä¹³é
žããªã¹ãã«ãšã¹
ãã«ãä¹³é
žã¹ãã¢ãªã«ãšã¹ãã«ãªã©ã®ã¢ã«ã³ãŒã«
æåã®ççŽ æ°ã12ã18ã®ãã®ã奜ãŸããåžåæ§ã
ããã
æ¬çºæã®äœçŽã¢ã«ã³ãŒã«ãšããŠã¯ããšãã«ã¢ã«
ã³ãŒã«ãå€æ§ã¢ã«ã³ãŒã«ããããã«ã¢ã«ã³ãŒã«å
ã³ãã³ãžã«ã¢ã«ã³ãŒã«ãªã©ã䜿çšããã
æ¬çºæã«ãããŠã¯ã該è»èå€ãåºäœç¶ã«ããçº
ã«ã²ã«åå€ãçšããã
ã²ã«åå€åã³ïŒåã¯å¢ç²å€ãšããŠã¯ãåŸæ¥é瀺
ãããïŒç¹å
¬æ56â10886ïŒã«ã«ããã·ããã«é
åäœãããããã·ãšãã«ã»ã«ããŒã¹ãã¡ãã«ã»ã«
ããŒã¹ã䜿çšåºæ¥ãä»ãããããã·ã¡ãã«ã»ã«ã
ãŒã¹ãããããã·ãšãã«ã»ã«ããŒã¹ãããããã·
ãããã«ã»ã«ããŒã¹ãã¡ãã«ã»ã«ããŒã¹ããšãã«
ã»ã«ããŒã¹çã®ååæç³»é«åååã³ã«ã©ã®ãŒãã³
ïœåååïŒãœã¢ã®ãŒãïŒäžè±ã¢ã»ããŒã(æ ª)ã®ã«ã©
ã®ãŒãã³ã®åååïŒïœïŒãã¢ãŒã»ã¬ã©ã³ïŒããŒã«ã¹
ãããŒã³ã¬ã ïœåååïŒãœã¢ããŒã«ã¹ãïŒäžè±ã¢
ã»ããŒã(æ ª)ã®ããŒã«ã¹ãããŒã³ã¬ã ã®åååïŒïœïŒ
ããµã³ã¿ã³ã¬ã çã®å€©ç¶ç³»é«ååãåç¬ã§åã¯äœµ
çšããŠçšããã
ãªããã«ã«ããã·ããã«éåäœãšããŠã¯ããã€
ãã¹ã¯ã³ãŒ103ïŒ104ïŒ105ïŒåååïŒåå
çŽè¬å·¥æ¥
æ ªåŒäŒç€Ÿè£œïŒãã«ãŒãããŒã«ïŒåååïŒã°ãããª
ããã±ãã«ã«ç€Ÿè£œïŒã䜿çšãããã
ãŸããã¡ãã«ã»ã«ããŒã¹åã³ããããã·ããã
ã«ã¡ãã«ã»ã«ããŒã¹ãšããŠã¯ãã¡ãããŒãºïŒåå
åïŒä¿¡è¶ååŠå·¥æ¥æ ªåŒäŒç€Ÿè£œïŒã䜿çšãããã
å°ååºå€ã®é
åéã¯äœ¿çšæãå®å®æ§ã溶解æ§å
ã³è¬å¹ãå
åã«çºæ®ãããããšçãããå¡©åºæ§ã¢
ããé
žã0.3ã10ééïŒ
ïŒå¥œãŸããã¯0.5ãïŒéé
ïŒ
ïŒãä¹³é
žãšã¹ãã«ã0.2ã10ééïŒ
ïŒå¥œãŸããã¯
0.5ãïŒééïŒ
ïŒãäœçŽã¢ã«ã³ãŒã«ã10ã60ééïŒ
ïŒå¥œãŸããã¯25ã40ééïŒ
ïŒã粟補氎ã20ã70éé
ïŒ
ïŒå¥œãŸããã¯40ã65ééïŒ
ïŒããã³ã³ã²ã«åå€
åã³ïŒåã¯å¢ç²å€ã0.2ãïŒééïŒ
ïŒå¥œãŸããã¯
ïŒãïŒééïŒ
ïŒãšãªãããã«æ··åããã®ãé©åœã§
ããã
次ã«æ¬çºæã®è£œé æ¹æ³ãšããŠã¯ã次ã®é åºã«åŸ
ã€ãŠæ··åããŠããã®ãè¯ãã
粟補氎ã«ã²ã«åå€åã³ïŒåã¯å¢ç²å€ãå ããŠ
èšæœ€ããæªæããã
ã€ã³ãã¡ã¿ã·ã³åã³åžåå©å€ãäœçŽã¢ã«ã³ãŒ
ã«æªæããªãã溶解ãããã
ã§æº¶è§£ããã溶液ãã®æº¶æ¶²ã«æ·»å ããæ°Ž
åãããŸã§ç空ç¶æ
ã§æªæããã
å¡©åºæ§ã¢ããé
žã粟補氎ã«æº¶è§£ããããã®ã
ã§æ°Žåããã液ã«æ·»å ãæªæããã
ã§æªæãã液ã«PH調æŽå€ãå ããŠæªæã
ãã
ãŸãåæªæå·¥çšã¯ã500ã3600rpmã§20åçšåºŠ
è¡ãªããã10000rpm以äžã§æªæãããšãã«ã¯å
åãåããªãããã«çãæéã§è¡ãªãããšãå¿
èŠ
ã§ããã
å°æ¬çºæã«ãããè»èå€ã«ã¯ãå¿
èŠã«å¿ããŠå
é
žåå€ãçé¢æŽ»æ§å€ãé²è
å€ãPH調æŽå€çãæ·»å
é
åããããšãå¯èœã§ããã
PH調æŽå€ãšããŠã¯ãšã³é
žããªã³ãŽé
žãé
ç³é
žã
ãžã€ãœãããããŒã«ã¢ãã³çã䜿çšããã
ç¹ã«ãžã€ãœãããããŒã«ã¢ãã³ã¯ãäžåå€ãšã
ãŠäœ¿çšããå Žåã«ãæ¬çºæåã«é¢ãéæ床ãé«ã
æ©èœãæããã
åè»èå€äžã«âã¡ã³ããŒã«ã0.25wïŒ
çšåºŠå
ããå Žåã«ã¯ãããã«ã€ã³ãã¡ã¿ã·ã³ã®åžåæ§ã
ãããªãã
ïŒçºæã®å¹æïŒ
æ¬çºæã«ãããè»èå€ã¯ãé·æéä¿åããŠãå®
å®ïŒé¢æ°Žã»å€è²ãã«ããïŒã§ããã
ã€ã³ãã¡ã¿ã·ã³ã®æº¶è§£å€ãšããŠãã°ãªã³ãŒã«é¡
ã§ã¯ãªãå¡©åºæ§ã¢ããé
žã䜿çšããŠããçºã«ãç®
èã«å¯Ÿããåºæ¿æ§ã匱ãã
åžåå€ãšããŠä¹³é
žãšã¹ãã«ã䜿çšããŠãããã
ã«ç®èãžã®åžåæ§ãè¯ãã
æ¬çºæã®è»èå€ã¯ãäžèšã®ãããªçµæãããªã
ãããã°ãªã³ãŒã«é¡ã䜿çšããå Žåãšç°ãªãã¹ãš
ã€ãããªããšããç¹åŸŽãæããã
以äžæ¬çºæãå®æœäŸã«åŸã€ãŠè©³çŽ°ã«èª¬æããã
ïŒå®æœäŸ ïŒïŒ
次ã®é
åéãããªãç©è³ªãäžèšã«ç€ºãæ¹æ³ã§ã
æ··åããŠè»èå€ãåŸãã
ïŒ ãœã¢ã®ãŒãïŒLXâïŒïŒ 1.6g
ïŒ ã¡ãããŒãºïŒ60SHâ4000ïŒ 0.3g
ïŒ ã€ã³ãã¡ã¿ã·ã³ 1.0g
ïŒ ä¹³é
žã¹ãã¢ãªã« 0.5g
ïŒ ãšã¿ããŒã« 30.0g
ïŒ ïŒ¬âã¢ã«ã®ãã³ 0.5g
ïŒ ãžã€ãœãããããŒã«ã¢ãã³ 0.8g
ïŒ ç²Ÿè£œæ°Ž åèš100gã«ããã«å
åãªé
(ã€) äžèšãœã¢ã®ãŒãåã³ã¡ãããŒãºã粟補氎20g
ã«èšæœ€ãããã
(ã) ã€ã³ãã¡ã¿ã·ã³ãä¹³é
žã¹ãã¢ãªã«åã³ãšã¿ã
ãŒã«ã«æº¶è§£ãããã
(ã) äžèš(ã)ã§æº¶è§£ããã液ã(ã€)ã®æº¶æ¶²ã«æ·»å ãæ°Ž
åãããŸã§æªæããã
(ã) äžèšïŒ¬âã¢ã«ã®ãã³ã粟補氎5gã«æº¶è§£ãã
ãåŸ(ã)ã®æ°Žåããã液ã«æ·»å ããã
(ã) ãžã€ãœãããããŒã«ã¢ãã³ã粟補氎5gã«æº¶
解ããããã«(ã)ã«æ·»å ããåŸãæ®éã®ç²Ÿè£œæ°Žã
å ããå
šäœãåäžã«ãªããŸã§æªæããã
(ã) 次ã«PH調æŽãè¡ãªãPH5.8ã®ã€ã³ãã¡ã¿ã·ã³
è»èãåŸãã
ïŒå®æœäŸ ïŒïŒ
次ã®é
åéãããªãç©è³ªãäžèšã«ç€ºãæ¹æ³ã§ã
æ··åããŠè»èå€ãåŸãã
ïŒ ãœã¢ã®ãŒãïŒLXâïŒïŒ 2.0g
ïŒ ã¡ãããŒãºïŒ60SHâ4000ïŒ 0.3g
ïŒ ã€ã³ãã¡ã¿ã·ã³ 1.0g
ïŒ ä¹³é
žã¹ãã¢ãªã« 0.5g
ïŒ ãšã¿ããŒã« 32.0g
ïŒ ïŒ¬âã¢ã«ã®ãã³ 0.4g
ïŒ ãžã€ãœãããããŒã«ã¢ãã³ 0.7g
ïŒ ç²Ÿè£œæ°Ž åèš100gã«ããã«å
åãªé
(ã€) äžèšãœã¢ã®ãŒãåã³ã¡ãããŒãºã粟補氎20g
ã«èšæœ€ãããã
(ã) ã€ã³ãã¡ã¿ã·ã³ãä¹³é
žã¹ãã¢ãªã«åã³ãšã¿ã
ãŒã«ã«æº¶è§£ãããã
(ã) äžèš(ã)ã§æº¶è§£ããã液ã(ã€)ã®æº¶æ¶²ã«æ·»å ãæ°Ž
åãããŸã§æªæããã
(ã)äžèšïŒ¬âã¢ã«ã®ãã³ã粟補氎5gã«æº¶è§£ããã
åŸ(ã)ã®æ°Žåããã液ã«æ·»å ããã
(ã)ãžã€ãœãããããŒã«ã¢ãã³ã粟補氎5gã«æº¶è§£
ããããã(ã)ã«æ·»å ããåŸãæ®éã®ç²Ÿè£œæ°Žãå
ããå
šäœãåäžã«ãªããŸã§æªæããã
(ã) 次ã«PH調æŽãè¡ãªãPH5.7ã®ã€ã³ãã¡ã¿ã·ã³
è»èãåŸãã
ïŒå®æœäŸ ïŒïŒ
次ã®é
åéãããªãç©è³ªãäžèšã«ç€ºãæ¹æ³ã§ã
æ··åããŠè»èå€ãåŸãã
ïŒ ãœã¢ã®ãŒãïŒLXâïŒïŒ 2.5g
ïŒ ã¡ãããŒãºïŒ60SHâ4000ïŒ 0.2g
ïŒ ã€ã³ãã¡ã¿ã·ã³ 1.0g
ïŒ ä¹³é
žã¹ãã¢ãªã« 0.2g
ïŒ ãšã¿ããŒã« 29.0g
ïŒ ïŒ¬âã¢ã«ã®ãã³ 0.6g
ïŒ ãžã€ãœãããããŒã«ã¢ãã³ 0.5g
ïŒ ç²Ÿè£œæ°Ž åèš100gã«ããã«å
åãªé
(ã€) äžèšãœã¢ã®ãŒãåã³ã¡ãããŒãºã粟補氎20g
ã«èšæœ€ãããã
(ã) ã€ã³ãã¡ã¿ã·ã³ãä¹³é
žã¹ãã¢ãªã«åã³ãšã¿ã
ãŒã«ã«æº¶è§£ãããã
(ã) äžèš(ã)ã§æº¶è§£ããã液ã(ã€)ã®æº¶æ¶²ã«æ·»å ãæ°Ž
åãããŸã§æªæããã
(ã) äžèšïŒ¬âã¢ã«ã®ãã³ã粟補氎5gã«æº¶è§£ãã
ãåŸ(ã)ã®æ°Žåããã液ã«æ·»å ããã
(ã) ãžã€ãœãããããŒã«ã¢ãã³ã粟補氎5gã«æº¶
解ããããã(ã)ã«æ·»å ããåŸãæ®éã®ç²Ÿè£œæ°Žã
å ããå
šäœãåäžã«ãªããŸã§æªæããã
(ã) 次ã«PH調æŽãè¡ãªãPH5.6ã®ã€ã³ãã¡ã¿ã·ã³
è»èãåŸãã
ïŒå®æœäŸ ïŒïŒ
次ã®é
åéãããªãç©è³ªãäžèšã«ç€ºãæ¹æ³ã§ã
æ··åããŠè»èå€ãåŸãã
ïŒ ãœã¢ã®ãŒãïŒMVâ201ïŒ 0.3g
ïŒ ã¡ãããŒãºïŒ60SHâ4000ïŒ 2.4g
ïŒ ã€ã³ãã¡ã¿ã·ã³ 1.0g
ïŒ ä¹³é
žã¹ãã¢ãªã« 1.5g
ïŒ ãšã¿ããŒã« 35.0g
ïŒ ïŒ¬âã¢ã«ã®ãã³ 1.0g
ïŒ ãžã€ãœãããããŒã«ã¢ãã³ 0.8g
ïŒ ç²Ÿè£œæ°Ž åèš100gã«ããã«å
åãªé
(ã€) äžèšãœã¢ã®ãŒãåã³ã¡ãããŒãºã粟補氎20g
ã«èšæœ€ãããã
(ã) ã€ã³ãã¡ã¿ã·ã³ãä¹³é
žã¹ãã¢ãªã«åã³ãšã¿ã
ãŒã«ã«æº¶è§£ãããã
(ã) äžèš(ã)ã§æº¶è§£ããã液ã(ã€)ã®æº¶æ¶²ã«æ·»å ãæ°Ž
åãããŸã§æªæããã
(ã) äžèšïŒ¬âã¢ã«ã®ãã³ã粟補氎5gã«æº¶è§£ãã
ãåŸ(ã)ã®æ°Žåããã液ã«æ·»å ããã
(ã) ãžã€ãœãããããŒã«ã¢ãã³ã粟補氎5gã«æº¶
解ããããã(ã)ã«æ·»å ããåŸãæ®éã®ç²Ÿè£œæ°Žã
å ããå
šäœãåäžã«ãªããŸã§æªæããã
(ã) 次ã«PH調æŽãè¡ãªãPH5.8ã®ã€ã³ãã¡ã¿ã·ã³
è»èãåŸãã
ïŒå®æœäŸâïŒïŒ
次ã®é
åéãããªãç©è³ªãäžèšã«ç€ºãæ¹æ³ã§ã
æ··åããŠè»èå€ãåŸãã
ïŒ ãœã¢ã®ãŒãïŒMVâ201ïŒ 0.6g
ïŒ ã¡ãããŒãºïŒ60SHâ4000ïŒ 2.8g
ïŒ ã€ã³ãã¡ã¿ã·ã³ 1.0g
ïŒ ä¹³é
žã©ãŠãªã« 1.5g
ïŒ ãšã¿ããŒã« 35.0g
ïŒ ãã³ãžã«ã¢ã«ã³ãŒã« 4.0g
ïŒ DLâãªãžã³ 1.0g
ïŒ ãžã€ãœãããããŒã«ã¢ãã³ 0.8g
ïŒ ç²Ÿè£œæ°Ž åèš100gã«ããã«å
åãªé
(ã€) äžèšãœã¢ã®ãŒãåã³ã¡ãããŒãºã粟補氎20g
ã«èšæœ€ãããã
(ã) ã€ã³ãã¡ã¿ã·ã³ãä¹³é
žã¹ãã¢ãªã«ããšã¿ããŒ
ã«åã³ãã³ãžã«ã¢ã«ã³ãŒã«ã«æº¶è§£ãããã
(ã) äžèš(ã)ã§æº¶è§£ããã液ã(ã€)ã®æº¶æ¶²ã«æ·»å ãæ°Ž
åãããŸã§æªæããã
(ã) äžèšDLâãªãžã³ã粟補氎5gã«æº¶è§£ãããåŸ
(ã)ã®æ°Žåããã液ã«æ·»å ããã
(ã) ãžã€ãœãããããŒã«ã¢ãã³ã粟補氎5gã«æº¶
解ããããã«(ã)ã«æ·»å ããåŸãæ®éã®ç²Ÿè£œæ°Žã
å ããå
šäœãåäžã«ãªããŸã§æªæããã
(ã) 次ã«PH調æŽãè¡ãªãPH5.8ã®ã€ã³ãã¡ã¿ã·ã³
è»èãåŸãã
ïŒå®æœäŸ ïŒïŒ
次ã®é
åéãããªãç©è³ªãäžèšã«ç€ºãæ¹æ³ã§ã
æ··åããŠè»èå€ãåŸãã
ïŒ ãœã¢ã®ãŒãïŒMVâ201ïŒ 0.3g
ïŒ ã¡ãããŒãºïŒ60SHâ4000ïŒ 2.6g
ïŒ ã€ã³ãã¡ã¿ã·ã³ 1.0g
ïŒ ä¹³é
žã©ãŠãªã« 1.5g
ïŒ ãšã¿ããŒã« 37.0g
ïŒ DLâãªãžã³ 1.0g
ïŒ ãžã€ãœãããããŒã«ã¢ãã³ 0.8g
ïŒ ç²Ÿè£œæ°Ž åèš100gã«ããã«å
åãªé
(ã€) äžèšãœã¢ã®ãŒãåã³ã¡ãããŒãºã粟補氎20g
ã«èšæœ€ãããã
(ã) ã€ã³ãã¡ã¿ã·ã³ãä¹³é
žã©ãŠãªã«åã³ãšã¿ããŒ
ã«ã«æº¶è§£ãããã
(ã) äžèš(ã)ã§æº¶è§£ããã液ã(ã€)ã®æº¶æ¶²ã«æ·»å ãæ°Ž
åãããŸã§æªæããã
(ã) äžèšDLâãªãžã³ã粟補氎5gã«æº¶è§£ãããåŸ
(ã)ã®æ°Žåããã液ã«æ·»å ããã
(ã) ãžã€ãœãããããŒã«ã¢ãã³ã粟補氎5gã«æº¶
解ããããã(ã)ã«æ·»å ããåŸãæ®éã®ç²Ÿè£œæ°Žã
å ããå
šäœãåäžã«ãªããŸã§æªæããã
(ã) 次ã«PH調æŽãè¡ãªãPH5.8ã®ã€ã³ãã¡ã¿ã·ã³
è»èãåŸãã
ïŒæ¯èŒäŸïŒç¹å
¬æ56â10886ïŒ
次ã®é
åéããæããã®ãäžèšã«ç€ºãæ¹æ³ã§æ··
åãã€ã³ãã¡ã¿ã·ã³è»èãåŸãã
ïŒ ãã€ãã¹ã¯ã³ãŒ104 1.0g
ïŒ ã€ã³ãã¡ã¿ã·ã³ 1.0g
ïŒ ãããã¬ã³ã°ãªã³ãŒã« 12.0g
ïŒ ãšã¿ããŒã« 30.0g
ïŒ ãžã€ãœãããã«ã¢ãžããŒã 2.0g
ïŒ ãžã€ãœãããããŒã«ã¢ãã³ 1.0g
ïŒ ç²Ÿè£œæ°Ž åèš100gã«ããã«å
åãªé
 äžèšïŒãæ°Ž20gã«èšæœ€ãããã
 äžèšïŒãäžèšïŒïŒïŒåã³ïŒã«æº¶è§£ãã
 äžèšïŒ¢ãäžèšïŒ¡ã«æ·»å ãå®å
šã«æ°ŽåãããŸã§
æªæããã
 äžèšïŒãæ°Ž10gã«æº¶è§£ããäžèšïŒ£ã«æ·»å ãã
ã®ã¡æ®éã®æ°Žãå ãå
šäœãåäžã«ãªããŸã§æªæ
ããã
以äžã®ããã«ããŠåŸãããæ¬çºæã«ãããå®æœ
äŸâïŒïŒå®æœäŸâïŒåã³æ¯èŒäŸã§ç€ºããæ¶çé®ç
è»èå€ã«ã€ããŠæ¬¡ã«ç€ºãæ¹æ³ã§ãããã®åžåçã«
ã€ããŠæ¯èŒæ€èšããã
å®éšæ¹æ³
ã¢ã«ã¢ããèéšç®èã®æ¯ãåããäžæ¥åŸçŽåŸ
2.5cmã®åå
ã«èª¿æŽããè»èå€0.1gãå¡åžããåŸã
ïŒæéåŸã«ååãããã®ååéã«ããåžåçãç®
åºããããã®çµæã¯ã次ã®ç€ºãéããšãªã€ãã
(Industrial Technical Field) The present invention relates to an anti-inflammatory analgesic ointment containing indomethacin as an active ingredient. Indomethacin is 1-(p-chlorobenzoyl)-5-methoxy-2-ethylindole-3
- Acetic acid (molecular formula: C 19 H 16 CINO 4 Molecular weight:
It is an excellent non-steroidal anti-inflammatory analgesic with the chemical name 357.79). (Prior Art) Indomethacin is a so-called non-steroidal anti-inflammatory analgesic that is widely used in the field of orthopedics for anti-inflammatory analgesic purposes, and the clinical effects of each have been confirmed. Most of these drugs are administered orally, and a small portion of them are parenterally administered in the form of suppositories. However, while oral non-steroidal anti-inflammatory analgesics have certain clinical effects, they are said to be destined to frequently cause side effects such as gastrointestinal disorders. For this reason, various attempts have been made to develop non-steroidal anti-inflammatory drugs with fewer side effects, but no drug has yet been developed that satisfies these requirements. Research on suppositories is being conducted with the aim of reducing side effects by devising the dosage form. However, although the side effects of suppositories have been slightly reduced compared to oral preparations, they still cause gastrointestinal disorders (e.g. nausea, vomiting, heartburn, diarrhea, abdominal pain, etc.).
(loss of appetite, headache, dizziness, etc.) have been observed. Therefore, suppositories must be administered with caution to patients with digestive system disorders. Therefore, in order to eliminate the side effects of such oral preparations and suppository forms, research is being carried out on ointments in which indomethacin is applied locally and absorbed into the skin. However, indomethacin has the property of being poorly soluble in water and common media. Therefore, even if indomethacin is added to the base of ointments, creams, etc. that are currently commonly used, it only exists in a suspended state in the base, and there is a problem with its absorption through the skin. There was a problem that a sufficient therapeutic effect could not be achieved. Recently, an anti-inflammatory and analgesic ointment (Japanese Patent Publication No. 10886-1983) has been known that eliminates this drawback and is made by gelling a combination of indomethacin, a medium consisting of glycols, lower alcohols, and water, and a gelling agent. ing. However, this anti-inflammatory analgesic ointment uses glycols (e.g. propylene glycol, polyethylene glycol, etc.) as a solubilizer for indomethacin.
It had the disadvantage of being highly irritating to the skin (prone to causing rashes) due to the use of large amounts. Also, as an absorption aid for indomethacin, C 4 to C 14
C1 - C5 alcohol esters of monocarboxylic acids and C1 - C3 alcohol diesters of C4 - C10 dicarboxylic acids (e.g. diisopropyl adibate, diethyl sebacate, etc.) are used, but the absorption rate is low. could not be said to be sufficient. Therefore, there has been a desire for an ointment containing indomethacin that is less irritating to the skin and has a higher absorption rate. (Problems to be Solved by the Invention) Therefore, in view of the drawbacks of the prior art, the present invention aims to provide an anti-inflammatory analgesic ointment that is less irritating to the skin and has good absorption of indomethacin into the skin. do. (Means for Solving the Problems) Therefore, in view of the actual state of the prior art, the present inventors aimed to reduce the side effects of non-steroidal anti-inflammatory analgesics, have low irritation to the skin, and have low absorption efficiency. As a result of intensive research in order to provide a high quality ointment, we found that using basic amino acids instead of glycols as a solubilizing agent will cause less irritation to the skin, and that using C 1 of C 4 to C 14 monocarboxylic acids as an absorption aid ~ C5
He discovered that absorption efficiency was high when lactic acid ester was used instead of alcohol ester of C4 to C10 dicarboxylic acid and alcohol diester of C1 to C3 of C4 to C10 dicarboxylic acid. That is, the present invention provides 0.5 to 1.5% by weight of indomethacin.
and a medium consisting of 0.3 to 10% by weight of basic amino acids, 10 to 60% by weight of lower alcohols, and 20 to 70% by weight of water, and an absorbent selected from the group consisting of 0.2 to 5% by weight of gelling agents and lactic acid esters. Auxiliary agent 0.2-10% by weight
This is an anti-inflammatory analgesic ointment containing the following. These smoke pain relief ointments are novel inventions that can overcome the drawbacks of the prior art, and have great practical value. The active ingredient of the present invention, indomethacin, is 0.5
The effect can be fully expected at ~1.5% by weight. In addition, the conditions that should be met for indomethacin as an ointment are that 0.5 to 1.5% by weight of indomethacin should be dissolved, it should have a refreshing feeling, it should have an excellent feeling of use, and it should have sufficient medicinal efficacy. It must be chemically stable. In general, the stability of indomethacin is largely influenced by its liquid properties, and is unstable in both strong acids and strong alkalis, and the desirable pH is considered to be 4.5 to 6.2. However, indomethacin has very low solubility in acidic conditions and has the problem of crystal precipitation, making it extremely difficult to obtain a stable indomethacin ointment. However, the anti-inflammatory analgesic ointment according to the present invention has a pH of 4.5 to 6.2 and is extremely stable. The basic amino acids used as the solubilizing agent of the present invention include lysine, arginine, orthinine,
Histidine and the like are preferred. However, the optical activity is L
It does not matter whether it is a body, D body, or DL body. As the lactic acid ester used as an absorption aid, those having an alcohol component having 12 to 18 carbon atoms, such as lactate lauryl ester, lactate myristyl ester, and lactate stearyl ester, are preferable because they have good absorbability. As the lower alcohol of the present invention, ethyl alcohol, denatured alcohol, propyl alcohol, benzyl alcohol, etc. are used. In the present invention, a gelling agent is used to make the ointment solid. As the gelling agent and/or thickening agent, carboxyvinyl polymers, hydroxyethyl cellulose, and methyl cellulose which have been previously disclosed (Japanese Patent Publication No. 56-10886) can also be used, as well as hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, and ethyl cellulose. Semi-synthetic polymers such as carrageenan {product name: Soagina (product name of carrageenan manufactured by Mitsubishi Acetate Co., Ltd.)}, fur-cerelan, locust bean gum {product name: Soar Locust (product name of locust bean gum produced by Mitsubishi Acetate Co., Ltd.) Product name)},
Natural polymers such as xanthan gum are used alone or in combination. As the carboxyvinyl polymer, Hivis Wako 103, 104, 105 (trade name, manufactured by Wako Pure Chemical Industries, Ltd.) and Carbopol (trade name, manufactured by Gutsudoritsuchi Chemical Co., Ltd.) are used. Furthermore, as the methylcellulose and hydroxypropylmethylcellulose, Metrose (trade name, manufactured by Shin-Etsu Chemical Co., Ltd.) is used. In addition, the blending amount of each base is 0.3 to 10% by weight (preferably 0.5 to 4% by weight) of basic amino acids and 0.2% of lactic acid ester in order to fully demonstrate the usability, stability, solubility, and medicinal efficacy. ~10% by weight (preferably
0.5-4% by weight), lower alcohol 10-60% by weight
(preferably 25-40% by weight), purified water 20-70% (preferably 40-65% by weight) and gelling agent and/or thickener 0.2-5% (preferably 1-4% by weight). % by weight). Next, in the manufacturing method of the present invention, it is preferable to mix according to the following order. A gelling agent and/or thickener is added to purified water to swell and stir. Indomethacin and absorption aid are dissolved in the lower alcohol with stirring. Add the solution dissolved in to the solution of and stir under vacuum until hydrated. A basic amino acid dissolved in purified water is added to the hydrated solution and stirred. Add the PH adjuster to the stirred solution and stir. Further, each stirring step is performed for about 20 minutes at 500 to 3,600 rpm, but when stirring at 10,000 rpm or more, it is necessary to perform the stirring for a short time so as not to break the molecules. Note that the ointment according to the present invention can also contain an antioxidant, a surfactant, a preservative, a PH regulator, etc., if necessary. Citric acid, malic acid, tartaric acid, as a PH regulator
Use diisopropanolamine etc. In particular, diisopropanolamine, when used as a neutralizing agent, has the function of increasing the transparency of the product of the present invention. Furthermore, when about 0.25 w% of -menthol is added to the ointment, the absorption of indomethacin is further improved. (Effects of the Invention) The ointment according to the present invention is stable (resistant to syneresis and discoloration) even when stored for a long period of time. Because it uses basic amino acids rather than glycols as a solubilizer for indomethacin, it is less irritating to the skin. It absorbs well into the skin because it uses lactic acid ester as an absorbent. Since the ointment of the present invention has the above-mentioned composition, it has the characteristic of not being sticky, unlike when glycols are used. The present invention will be described in detail below with reference to Examples. (Example 1) A substance consisting of the following blending amounts was prepared by the method shown below.
Mix to obtain an ointment. 1 Soagina (LX-7) 1.6g 2 Metrose (60SH-4000) 0.3g 3 Indomethacin 1.0g 4 Stearyl lactate 0.5g 5 Ethanol 30.0g 6 L-Arginine 0.5g 7 Diisopropanolamine 0.8g 8 Purified water Make a total of 100g Sufficient amount (a) 20g of the above Soagina and Metrose in purified water
to swell. (b) Dissolve indomethacin in stearyl lactate and ethanol. (c) Add the solution dissolved in (b) above to the solution in (a) and stir until hydrated. (d) Dissolve the above L-arginine in 5 g of purified water, and then add to the hydrated solution of (c). (e) Dissolve diisopropanolamine in 5 g of purified water, add it to (d), then add the remaining amount of purified water and stir until the whole is homogeneous. (f) Next, the pH was adjusted to obtain indomethacin ointment with a pH of 5.8. (Example 2) A substance consisting of the following blending amounts was prepared by the method shown below.
Mix to obtain an ointment. 1 Soagina (LX-8) 2.0g 2 Metrose (60SH-4000) 0.3g 3 Indomethacin 1.0g 4 Stearyl lactate 0.5g 5 Ethanol 32.0g 6 L-Arginine 0.4g 7 Diisopropanolamine 0.7g 8 Purified water Make a total of 100g Sufficient amount (a) 20g of the above Soagina and Metrose in purified water
to swell. (b) Dissolve indomethacin in stearyl lactate and ethanol. (c) Add the solution dissolved in (b) above to the solution in (a) and stir until hydrated. (d) Dissolve the above L-arginine in 5 g of purified water, and then add to the hydrated solution of (c). (e) Dissolve diisopropanolamine in 5 g of purified water, add this to (d), then add the remaining amount of purified water and stir until the whole is homogeneous. (F) Next, the pH was adjusted to obtain indomethacin ointment with a pH of 5.7. (Example 3) A substance consisting of the following blending amounts was prepared by the method shown below.
Mix to obtain an ointment. 1 Soagina (LX-9) 2.5g 2 Metrose (60SH-4000) 0.2g 3 Indomethacin 1.0g 4 Stearyl lactate 0.2g 5 Ethanol 29.0g 6 L-Arginine 0.6g 7 Diisopropanolamine 0.5g 8 Purified water Make a total of 100g Sufficient amount (a) 20g of the above Soagina and Metrose in purified water
to swell. (b) Dissolve indomethacin in stearyl lactate and ethanol. (c) Add the solution dissolved in (b) above to the solution in (a) and stir until hydrated. (d) Dissolve the above L-arginine in 5 g of purified water, and then add to the hydrated solution of (c). (e) Dissolve diisopropanolamine in 5 g of purified water, add this to (d), then add the remaining amount of purified water and stir until the whole is homogeneous. (F) Next, the pH was adjusted to obtain indomethacin ointment with a pH of 5.6. (Example 4) A substance consisting of the following blending amounts was prepared by the method shown below.
Mix to obtain an ointment. 1 Soagina (MV-201) 0.3g 2 Metrose (60SH-4000) 2.4g 3 Indomethacin 1.0g 4 Stearyl lactate 1.5g 5 Ethanol 35.0g 6 L-Arginine 1.0g 7 Diisopropanolamine 0.8g 8 Purified water Make a total of 100g Sufficient amount (a) 20g of the above Soagina and Metrose in purified water
to swell. (b) Dissolve indomethacin in stearyl lactate and ethanol. (c) Add the solution dissolved in (b) above to the solution in (a) and stir until hydrated. (d) Dissolve the above L-arginine in 5 g of purified water, and then add to the hydrated solution of (c). (e) Dissolve diisopropanolamine in 5 g of purified water, add this to (d), then add the remaining amount of purified water and stir until the whole is homogeneous. (f) Next, adjust the pH to obtain indomethacin ointment with a pH of 5.8. (Example-5) A substance consisting of the following blending amount was prepared by the method shown below.
Mix to obtain an ointment. 1 Soagina (MV-201) 0.6g 2 Metrose (60SH-4000) 2.8g 3 Indomethacin 1.0g 4 Lauryl lactate 1.5g 5 Ethanol 35.0g 6 Benzyl alcohol 4.0g 6 DL-lysine 1.0g 7 Diisopropanolamine 0.8g 8 Purification Sufficient amount of water to make a total of 100g (a) 20g of purified water with the above Soagina and Metrose
to swell. (b) Dissolve indomethacin in stearyl lactate, ethanol, and benzyl alcohol. (c) Add the solution dissolved in (b) above to the solution in (a) and stir until hydrated. (d) After dissolving the above DL-lysine in 5 g of purified water
Add to the hydrated solution in (c). (e) Dissolve diisopropanolamine in 5 g of purified water, add it to (d), then add the remaining amount of purified water and stir until the whole is homogeneous. (f) Next, adjust the pH to obtain indomethacin ointment with a pH of 5.8. (Example 6) A substance consisting of the following blending amount was prepared by the method shown below.
Mix to obtain an ointment. 1 Soagina (MV-201) 0.3g 2 Metrose (60SH-4000) 2.6g 3 Indomethacin 1.0g 4 Lauryl lactate 1.5g 5 Ethanol 37.0g 6 DL-lysine 1.0g 7 Diisopropanolamine 0.8g 8 Purified water Make a total of 100g Sufficient amount (a) 20g of the above Soagina and Metrose in purified water
to swell. (b) Dissolve indomethacin in lauryl lactate and ethanol. (c) Add the solution dissolved in (b) above to the solution in (a) and stir until hydrated. (d) After dissolving the above DL-lysine in 5 g of purified water
Add to the hydrated solution in (c). (e) Dissolve diisopropanolamine in 5 g of purified water, add this to (d), then add the remaining amount of purified water and stir until the whole is homogeneous. (f) Next, the pH was adjusted to obtain indomethacin ointment with a pH of 5.8. (Comparative Example: Japanese Patent Publication No. 56-10886) Indomethacin ointment is obtained by mixing the following amounts in the method shown below. 1 Hibis Wako 104 1.0g 2 Indomethacin 1.0g 3 Propylene glycol 12.0g 4 Ethanol 30.0g 5 Diisopropyl adipate 2.0g 6 Diisopropanolamine 1.0g 7 Purified water Enough amount to make a total of 100g A Swell the above 1 in 20g of water let B. Dissolve 2 above in 3, 4, and 5. C. Add B above to A and stir until completely hydrated. D Dissolve the above 6 in 10 g of water, add it to the above C, then add the remaining amount of water and stir until the whole becomes uniform. The absorption rates of the anti-inflammatory and analgesic ointments shown in Example-1, Example-5 and Comparative Example of the present invention obtained as described above were compared and studied using the following method. Experimental method The hair on the dorsal skin of guinea pigs was shaved, and the diameter was measured one day later.
After applying 0.1g of the adjusted ointment within a 2.5cm circle,
It was collected after 5 hours, and the absorption rate was calculated from the collected amount. The results were as shown below.
ãè¡šã
å°ãä»ã®å®æœäŸã«ã€ããŠããåžåçã«é¢ããæ¯
èŒäŸã®ãã®ãããåªäœæ§ãã¿ãããã[Table] It should be noted that the other Examples also showed superiority over the Comparative Examples in terms of absorption rate.
Claims (1)
ãŒã«10ã60ééïŒ åã³æ°Ž20ã70ééïŒ ãããªã
åªäœ (ã) ã²ã«åå€åã³ïŒåã¯å¢ç²å€0.2ãïŒééïŒ (ã) ä¹³é žãšã¹ãã«ãããªã矀ããéžã°ããåžåå©
å€0.2ã10ééïŒ ãšãé åããŠãªãæ¶çé®çè»èå€ã ïŒ å¡©åºæ§ã¢ããé žãããªãžã³ãã¢ã«ã®ãã³ãã
ã¹ããžã³åã¯ãªã«ããã³ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬
ïŒé èšèŒã®æ¶çé®çè»èå€ã ïŒ ã²ã«åå€åã³ïŒåã¯å¢ç²å€ããã«ã©ã®ãŒã
ã³ããã¢ãŒã»ã¬ã©ã³ãããŒã«ã¹ãããŒã³ã¬ã ãã
ãµã³ã¿ã³ã¬ã çã®å€©ç¶ç³»é«ååãããããã·ã¡ã
ã«ã»ã«ããŒã¹ãããããã·ãšãã«ã»ã«ããŒã¹ãã
ãããã·ãããã«ã»ã«ããŒã¹ãããããã·ããã
ã«ã¡ãã«ã»ã«ããŒã¹ãã«ã«ããã·ã¡ãã«ã»ã«ããŒ
ã¹ããšãã«ã»ã«ããŒã¹ãã¡ãã«ã»ã«ããŒã¹çã®å
åæç³»é«ååããã³ã«ã«ããã·ããã«éåäœçã®
åæç³»é«ååã§ãããå°ãªããšãäžçš®ä»¥äžäœ¿çšã
ãç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé åã¯ç¬¬ïŒé èšèŒã®æ¶çé®
çè»èå€ã ïŒ ä¹³é žãšã¹ãã«ãããã®ã¢ã«ã³ãŒã«æåã®ççŽ
æ°ã12ã18ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ïŒç¬¬ïŒ
é ïŒç¬¬ïŒé ã®ããããïŒé èšèŒã®æ¶çé®çè»è
å€ã[Scope of Claims] 1. The following components (a), (b), (c) and (d) (a) 0.5 to 1.5% by weight of indomethacin (b) 0.3 to 10% by weight of basic amino acids, 10 to 10% by weight of lower alcohols 60% by weight of medium and 20-70% by weight of water (c) 0.2-5% by weight of gelling agent and/or thickener (d) 0.2-10% by weight of absorption aid selected from the group consisting of lactic acid esters An anti-inflammatory analgesic ointment containing the following. 2. The anti-inflammatory analgesic ointment according to claim 1, wherein the basic amino acid is lysine, arginine, histidine, or orthinine. 3. The gelling agent and/or thickener is a natural polymer such as carrageenan, furcerelan, locust bean gum, xanthan gum, etc., hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, ethyl cellulose, methyl cellulose, etc. The anti-inflammatory and analgesic ointment according to claim 1 or 2, which is a synthetic polymer such as a semi-synthetic polymer and a carboxyvinyl polymer, and uses at least one kind thereof. 4. Claims 1 and 2 in which the alcohol component of the lactic acid ester has 12 to 18 carbon atoms.
The anti-inflammatory and analgesic ointment according to any one of Items 1 and 3.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP60178394A JPS6239524A (en) | 1985-08-13 | 1985-08-13 | Anti-inflammatory analgesic ointment |
KR1019850008701A KR890002239B1 (en) | 1985-05-30 | 1985-11-21 | Process for preparation of indometacin ointment |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP60178394A JPS6239524A (en) | 1985-08-13 | 1985-08-13 | Anti-inflammatory analgesic ointment |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6239524A JPS6239524A (en) | 1987-02-20 |
JPH0434971B2 true JPH0434971B2 (en) | 1992-06-09 |
Family
ID=16047730
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP60178394A Granted JPS6239524A (en) | 1985-05-30 | 1985-08-13 | Anti-inflammatory analgesic ointment |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6239524A (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0720866B2 (en) * | 1987-05-15 | 1995-03-08 | äžç補è¬æ ªåŒäŒç€Ÿ | Transdermal preparation containing eperisone or tolperisone or their salts |
GB8929076D0 (en) * | 1989-12-22 | 1990-02-28 | Scras | Treatment of shock by blocking agents of edrf effect or formation |
-
1985
- 1985-08-13 JP JP60178394A patent/JPS6239524A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS6239524A (en) | 1987-02-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0184389B1 (en) | Composition stably containing minocycline for treating periodontal diseases | |
US4678666A (en) | Topical anti-inflammatory compositions | |
WO1992007561A1 (en) | Antiphlogistic and analgesic gel preparation | |
MX2008015599A (en) | Topical compositions. | |
JP2010195823A (en) | Injectable veterinary composition for small animals | |
JP2021152080A (en) | Pharmaceutical composition | |
JP2523428B2 (en) | Anti-inflammatory analgesic gel formulation | |
JP4195178B2 (en) | Anti-inflammatory analgesic topical | |
JP3802105B2 (en) | Diclofenac sodium-containing emulsified external preparation | |
EP0416804B1 (en) | External preparation containing amusulosin | |
JPH0434971B2 (en) | ||
JPH0236570B2 (en) | SHOENCHINT SUNANKOZAI | |
WO2004030665A1 (en) | Transparent gel composition, for the administration of diclofenac sodium through the skin | |
JPH07267839A (en) | Ointment composition adhesive to oral mucosa | |
JP2021152081A (en) | Pharmaceutical composition | |
JPH1029937A (en) | Pharmaceutical preparation of mefenamic acid aqueous solution | |
JP6871086B2 (en) | Pharmaceutical composition | |
EP1242062B1 (en) | Anhydrous gel comprising nsaid for topical administration to the oral cavity | |
JP3273506B2 (en) | Pharmaceutical composition for transdermal administration | |
WO2007046318A1 (en) | Liquid preparation for external application containing indomethacin | |
KR890002239B1 (en) | Process for preparation of indometacin ointment | |
JPH069394A (en) | External antiphlogistic sedative liquid preparation | |
EP2340016A2 (en) | Topical formulation of 3-(2,2,2-trimethylhydrazinium) propionate dihydrate | |
JP2004131472A (en) | Ointment for treatment of hemorrhoid | |
JPH05117141A (en) | Antiinflammatory analgesic gel preparation containing adrenal essence |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
LAPS | Cancellation because of no payment of annual fees |