DE1195296B - Process for the preparation of anti-inflammatory and edema-inhibiting salts of cis-9-pentadecenoic acid and cis-9-heptadecenoic acid - Google Patents
Process for the preparation of anti-inflammatory and edema-inhibiting salts of cis-9-pentadecenoic acid and cis-9-heptadecenoic acidInfo
- Publication number
- DE1195296B DE1195296B DEG33786A DEG0033786A DE1195296B DE 1195296 B DE1195296 B DE 1195296B DE G33786 A DEG33786 A DE G33786A DE G0033786 A DEG0033786 A DE G0033786A DE 1195296 B DE1195296 B DE 1195296B
- Authority
- DE
- Germany
- Prior art keywords
- acid
- cis
- salts
- pentadecenoic
- heptadecenoic
- 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.)
- Pending
Links
- 150000003839 salts Chemical class 0.000 title claims description 19
- QSBYPNXLFMSGKH-HJWRWDBZSA-N (9Z)-heptadecenoic acid Chemical class CCCCCCC\C=C/CCCCCCCC(O)=O QSBYPNXLFMSGKH-HJWRWDBZSA-N 0.000 title claims description 10
- DJCQJZKZUCHHAL-SREVYHEPSA-N (z)-pentadec-9-enoic acid Chemical class CCCCC\C=C/CCCCCCCC(O)=O DJCQJZKZUCHHAL-SREVYHEPSA-N 0.000 title claims description 10
- 230000003501 anti-edematous effect Effects 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 5
- 230000003110 anti-inflammatory effect Effects 0.000 title claims description 4
- 230000002401 inhibitory effect Effects 0.000 title description 2
- 238000002360 preparation method Methods 0.000 title description 2
- 206010030113 Oedema Diseases 0.000 title 1
- 239000002253 acid Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 238000005984 hydrogenation reaction Methods 0.000 claims description 9
- 239000007868 Raney catalyst Substances 0.000 claims description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 4
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 150000002780 morpholines Chemical class 0.000 claims description 3
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 8
- 159000000000 sodium salts Chemical class 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- -1 undecylenic acid Chemical class 0.000 description 4
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 3
- 229940117173 croton oil Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229960002703 undecylenic acid Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XMVQWNRDPAAMJB-UHFFFAOYSA-N (+)-13-Cyclopent-2-enyl-tridecansaeure Natural products OC(=O)CCCCCCCCCCCCC1CCC=C1 XMVQWNRDPAAMJB-UHFFFAOYSA-N 0.000 description 2
- XMVQWNRDPAAMJB-QGZVFWFLSA-N (S)-chaulmoogric acid Chemical compound OC(=O)CCCCCCCCCCCC[C@H]1CCC=C1 XMVQWNRDPAAMJB-QGZVFWFLSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ASXBYYWOLISCLQ-UHFFFAOYSA-N Dihydrostreptomycin Natural products O1C(CO)C(O)C(O)C(NC)C1OC1C(CO)(O)C(C)OC1OC1C(N=C(N)N)C(O)C(N=C(N)N)C(O)C1O ASXBYYWOLISCLQ-UHFFFAOYSA-N 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 2
- 206010018691 Granuloma Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- ASXBYYWOLISCLQ-HZYVHMACSA-N dihydrostreptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](CO)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O ASXBYYWOLISCLQ-HZYVHMACSA-N 0.000 description 2
- 229960002222 dihydrostreptomycin Drugs 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000001126 granulation tissue Anatomy 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- RGTIBVZDHOMOKC-UHFFFAOYSA-N stearolic acid Chemical compound CCCCCCCCC#CCCCCCCCC(O)=O RGTIBVZDHOMOKC-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- SRELFLQJDOTNLJ-HNNXBMFYSA-N (R)-hydnocarpic acid Chemical compound OC(=O)CCCCCCCCCC[C@@H]1CCC=C1 SRELFLQJDOTNLJ-HNNXBMFYSA-N 0.000 description 1
- AWBXTNNIECFIHT-XZQQZIICSA-N 2-[(1r,2r,3s,4r,5r,6s)-3-(diaminomethylideneamino)-4-[(2r,3r,4r,5s)-3-[(2s,3s,4s,5r,6s)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine;2-[(1r,2r,3s,4r,5r,6s)-3-( Chemical class CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](CO)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O AWBXTNNIECFIHT-XZQQZIICSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- VMBXKUPZOMUHQT-UHFFFAOYSA-N 5-ethyl-5-pentan-3-yl-2-sulfanylidene-1,3-diazinane-4,6-dione Chemical compound CCC(CC)C1(CC)C(=O)NC(=S)NC1=O VMBXKUPZOMUHQT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- SRELFLQJDOTNLJ-UHFFFAOYSA-N Hydnocarpic acid Natural products OC(=O)CCCCCCCCCCC1CCC=C1 SRELFLQJDOTNLJ-UHFFFAOYSA-N 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000021319 Palmitoleic acid Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000011805 ball Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 230000037313 granulation tissue formation Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- GEHPRJRWZDWFBJ-UHFFFAOYSA-N heptadec-2-enoic acid Chemical class CCCCCCCCCCCCCCC=CC(O)=O GEHPRJRWZDWFBJ-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/03—Monocarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/36—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von entzündungs-und ödemhemmenden Salzen der cis-9-Pentadecensäure und der cis-9-Heptadecensäure Es wurde gefunden, daß die Salze der cis-9-Pentadecensäure und der cis-9-Heptadecensäure mit physiologisch verträglichen Basen wertvolle pharmakologische Eigenschaften besitzen. Besonders zeigen diese Verbindungen im menschlichen und tierischen Körper eine entzündungs- und ödemhemmende Wirkung. Bei der Prüfung der biologischen Wirkung der erwähnten Verbindungen wurde im Tierversuch vorzugsweise das Hauttaschengranulom der Ratte nach Selye (vgl.Process for the preparation of anti-inflammatory and anti-edema salts the cis-9-pentadecenoic acid and the cis-9-heptadecenoic acid It was found that the Salts of cis-9-pentadecenoic acid and cis-9-heptadecenoic acid with physiological compatible bases have valuable pharmacological properties. Particularly show these compounds in the human and animal body an inflammatory and anti-edema effect. When examining the biological effects of the mentioned Compounds in animal experiments were preferably the skin pocket granuloma of the rat according to Selye (cf.
Progress in Hormone Research, Bd. 8, 1953, S. 117, JournalAmer. Med. Association, Bd. 152,1953, S.1207) verwendet. Der biologische Versuch wurde mit genetisch einheitlich entwickelten Ratten durchgeführt.Progress in Hormone Research, Vol. 8, 1953, p. 117, JournalAmer. Med. Association, Vol. 152, 1953, p. 1207). The biological experiment was with genetically uniformly developed rats.
Den Ratten wurden in der Narkose, erzeugt durch intraperitoneales Einspritzen von 50 mg je Kilogramm Körpergewicht des Natriumsalzes der 5-Äthyl-5-(l -methyl-2-butyl)-thiobarbitursäure, bekannt unter dem Warenzeichen )>Trapanal«, nach dem Rasieren und Jodieren der Rückenhaut etwa 15 ccm Luft aus steriler Spritze subkutan unter die Rückenhaut verabfolgt. The rats were anesthetized by intraperitoneal anesthesia Injection of 50 mg per kilogram of body weight of the sodium salt of 5-ethyl-5- (l -methyl-2-butyl) thiobarbituric acid, known under the trademark)> Trapanal ", after shaving and iodising the skin on the back, about 15 ccm of air from a sterile syringe administered subcutaneously under the skin of the back.
Unmittelbar anschließend erfolgte unter sterilen Bedingungen jeweils durch die gleiche Kanüle die Zufuhr von zuerst 0,5 ml 1°/Oigem Crotonöl in Olivenöl, dann von 5 mg des Natriumsalzes einer der nachstehenden Säuren a) bis d) in die Hauttasche, wobei die 5 mg Natriumsalz in 0,5 ccm Wasser gelöst waren und der pH-Wert der Lösung 7,8 betrug. Die Tötung der Ratten erfolgte 96 Stunden nach Versuchsbeginn. Die histologische Aufarbeitung wurde wie üblich durchgeführt.Immediately thereafter, in each case, under sterile conditions through the same cannula the supply of first 0.5 ml 1% croton oil in olive oil, then from 5 mg of the sodium salt of one of the following acids a) to d) in the Skin pocket, where the 5 mg sodium salt were dissolved in 0.5 ccm water and the pH value the solution was 7.8. The rats were killed 96 hours after the start of the experiment. The histological work-up was carried out as usual.
Die Auswertung erfolgte auf Grund der histologischen Befunde. Die Breite des Granulations- gewebswalles und das aus der Kerndichte abzuleitende Maß für die Stärke der Entzündung dienten als Grundlage für die Bewertung. The evaluation was based on the histological findings. the Width of the granulation tissue wall and the measure to be derived from the core density for the strength of the inflammation served as the basis for the assessment.
Die Wertungsziffer 0 bedeutet keine Hemmung, 1 eine geringe bzw. angedeutete, 2 eine deutliche und 3 eine völlige Unterdrückung der Entzündung und Granulationsgewebsbildung. In Zweifelsfällen wurden abgestufte Werte, wie 0,5, 1,5, 2,5, verteilt. Den Vergleichstieren wurde jeweils nur Crotonöl verabfolgt. The rating number 0 means no inhibition, 1 a slight or indicated, 2 marked and 3 complete suppression of inflammation and Granulation tissue formation. In cases of doubt, graduated values such as 0.5, 1.5, 2.5 distributed. The comparison animals were given only croton oil in each case.
Auf Grund der vorstehenden Bewertung ergaben sich für die angewandten
Säuren folgende Ergebnisse
Auf die gleiche Weise wurden auch die Natriumsalze der geradzahligen und ungeradzahligen gesättigten Fettsäuren mit 11 bis 19 Kohlenstoffatomen geprüft; sie zeigten sämtlich keine Wirkung (Wertziffer 0). In the same way, the sodium salts became the even-numbered ones and odd-numbered saturated fatty acids with 11 to 19 carbon atoms tested; none of them showed any effect (digit 0).
Gleichfalls unwirksam waren die Natriumsalze anderer (nicht in der Tabelle aufgeführter) ungesättigter Fettsäuren, wie der Ölsäure, Palmitoleinsäure, Tetradecen-und Dodecensäure.The sodium salts of others (not in the Table of unsaturated fatty acids, such as oleic acid, palmitoleic acid, Tetradecenoic and dodecenoic acids.
In klinischen Untersuchungen ergab sich, daß die neuen Salze eine gute Wirksamkeit in bezug auf das Heilungsvermögen bei Hautschäden, z. B. infolge akuter oder chronischer Hautentzündung (Dermatitis), der Verwendung von Gipsbinden, infizierter Wunden oder Brandwunden niederen Grades, besitzen. In clinical studies it has been found that the new salts have a good effectiveness in terms of healing ability for skin damage, e.g. B. as a result acute or chronic inflammation of the skin (dermatitis), the use of plaster bandages, infected wounds or low-grade burns.
Es ist überraschend, daß die Salze nach der Erfindung befähigt sind, im menschlichen und tierischen Körper Wirkungen der erwähnten Art auszuüben. Es war lediglich bisher bekannt, daß die niedermolekularen Fettsäuren, wie die Undecylensäure, eine fungizide Wirkung und die höhermolekularen Fettsäuren, die in ihrem Molekül einen Ring mit 4 bis 6 Kohlenstoffatomen enthalten, wie die Chaulmoograsäure, eine antilepröse und antituberkulöse Wirkung besitzen. Hiervon ausgehend hat man auch schon Salze des Streptomycins und des Dihydrostreptomycins mit Propionsäure, Caprylsäure, Undecylensäure, Chaulmoograsäure und Hydnocarpussäure hergestellt und dadurch die Wirksamkeit des Streptomycins bzw. des Dihydrostreptomycins gegen Typhus, Lepra und Tuberkulose verbessert. Diese bekannten Tatsachen ließen nicht die vorerwähnten Wirkungen der Salze der cis-9-Pentadecensäure und der cis-9-Heptadecensäure mit physiologisch verträglichen Basen voraussehen. It is surprising that the salts according to the invention are capable of to exert effects of the type mentioned in the human and animal body. It it was only previously known that the low molecular weight fatty acids, such as undecylenic acid, a fungicidal effect and the higher molecular weight fatty acids in their molecule contain a ring with 4 to 6 carbon atoms, such as chaulmoogric acid, a Have anti-depressant and anti-tubercular effects. Starting from this one also has already salts of streptomycin and dihydrostreptomycin with propionic acid, caprylic acid, Undecylenic acid, chaulmoogric acid and hydnocarpic acid and thereby the Effectiveness of streptomycin or dihydrostreptomycin against typhoid and leprosy and tuberculosis improved. These known facts did not leave the aforementioned Effects of the salts of cis-9-pentadecenoic acid and cis-9-heptadecenoic acid with foresee physiologically compatible bases.
Das deutsche Patent 1147221 betrifft ein Verfahren zur Herstellung von entzündungs- und ödemhemmenden Salzen der Pentadecen- und Heptadecensäuren, das dadurch gekennzeichnet ist, daß man die cis-9-Pentadecensäure oder die cis-9-Heptadecensäure in an sich bekannter Weise mit einer physiologisch verträglichen Base in das Salz, vorzugsweise in das Natrium- oder Kaliumsalz, überführt. German patent 1147221 relates to a method of manufacture of anti-inflammatory and anti-edema salts of pentadecenoic and heptadecenoic acids, which is characterized in that the cis-9-pentadecenoic acid or the cis-9-heptadecenoic acid in a manner known per se with a physiologically compatible base in the salt, preferably converted into the sodium or potassium salt.
Nach dem Verfahren der Erfindung werden die Salze der cis-9-Pentadecensäure und der cis-9-Heptadecensäure von physiologisch verträglichen Basen dadurch hergestellt, daß man ein derartiges Salz der 9-Pentadecinsäure oder der 9-Heptadecinsäure mit Wasserstoff in Gegenwart von Raney-Nickel als Katalysator bis zur Aufnahme von 1 Mol Wasserstoff je Mol Carbonsäure hydriert. Dieser Weg ist technisch besonders einfach und vorteilhaft, weil die 9-Heptadecin- und die 9-Pentadecinsäure in reiner Form erhältlich sind und die Anlagerung von Wasserstoff an diese Carbonsäuren überraschenderweise ausschließlich zur Bildung der cis-Säuren führt. According to the process of the invention, the salts of cis-9-pentadecenoic acid and the cis-9-heptadecenoic acid produced from physiologically compatible bases, that such a salt of 9-pentadecinic acid or 9-heptadecinic acid with Hydrogen in the presence of Raney nickel as a catalyst until 1 Moles of hydrogen per mole of carboxylic acid hydrogenated. This path is technically special simple and advantageous because the 9-heptadecinic and 9-pentadecinic acids are more pure Form are available and the addition of hydrogen to these carboxylic acids surprisingly leads exclusively to the formation of the cis acids.
Als salzbildende Reste sind solche Basen verwendbar, die gegenüber dem menschlichen oder tierischen Körper physiologisch verträglich sind. Geeignete Salze sind besonders die Natrium- und Kaliumsalze sowie die Salze physiologisch verträglicher organischer Basen, wie die Äthanolamin-, Äthylendiamin-, p-Ami- nobenzoesäurediäthylaminoäthylester- (bekannt unter der Handelsbezeichnung »Procain(() und Morpholinsalze. Nach einer bevorzugten Ausführungsform der Erfindung werden als Salzbildner solche physiologisch verträglichen Basen verwendet, die eine die Wirkung der neuen Salze ergänzende, eigene Wirkung besitzen. The bases which can be used as salt-forming radicals are those which are opposite are physiologically compatible with the human or animal body. Suitable Salts are especially the sodium and potassium salts as well as the salts physiological compatible organic bases, such as the ethanolamine, ethylenediamine, p-ami- nobenzoesäurediethylaminoäthylester- (Known under the trade name »Procaine (() and morpholine salts. According to a Preferred embodiment of the invention are those which are physiological as salt formers compatible bases are used, which complement the effect of the new salts, have their own effect.
Hierzu gehören z. B. das Streptomycin, Dihydrostreptomycin, Isonicotinsäurehydrazid und die p-Aminosalicylsäure. Soweit die Salze in Wasser schwer löslich sind, können sie in der Form von Aufschlämmungen verabreicht werden. Eine besonders gute Löslichkeit in Wasser besitzen die Natrium- und die Kaliumsalze der cis-9-Heptadecensäure und der cis-9-Pentadecensäure.These include B. streptomycin, dihydrostreptomycin, isonicotinic acid hydrazide and p-aminosalicylic acid. As far as the salts are sparingly soluble in water, can they are administered in the form of slurries. A particularly good solubility in water have the sodium and potassium salts of cis-9-heptadecenoic acid and of cis-9-pentadecenoic acid.
Die Salze werden vorzugsweise in der Form einer wäßrigen Lösung, wie physiologische Kochsalzlösung, intravenös oder intramuskulär gespritzt. Die Ampullen enthalten z. B. 2,5 mg des fettsauren Salzes je 5 ml Lösung. Man kann auch Ampullen mit z. B. 45 mg fettsaurem Salz je Milliliter Lösung herstellen. Die Lösungen haben den Vorzug, daß sie isotonisch sind und ohne die Zugabe von Fremdkörpern hergestellt und verwendet werden können. Die Zugabe von Natriumchlorid ist bei der Herstellung dieser hochkonzentrierten Lösungen zu vermeiden, weil dieses auf die Fettsäuren ausfällend wirkt. Die fettsauren Salze können ferner peroral in der Form von Tabletten, Dragees, Vaginalkugeln, Zäpfchen oder Salben angewendet werden. The salts are preferably in the form of an aqueous solution, like physiological saline, injected intravenously or intramuscularly. the Ampoules contain z. B. 2.5 mg of the fatty acid salt per 5 ml of solution. One can also Ampoules with z. B. produce 45 mg of fatty acid salt per milliliter of solution. The solutions have the merit that they are isotonic and made without the addition of foreign bodies and can be used. The addition of sodium chloride is in the making Avoid these highly concentrated solutions because this affects the fatty acids acts precipitating. The fatty acid salts can also be taken orally in the form of tablets, Dragees, vaginal balls, suppositories or ointments are used.
Beispiel 1 3,0 g Kalium-9-heptadecinat werden in 50 ml Methanol gelöst. Die Lösung wird in eine mit Wasserstoff vorhydrierte Lösung von Raney-Nickel in Methanol getropft. Nachdem die Lösung vollständig zugetropft ist, erfolgt die Wasserstoffaufnahme in einer üblichen Hydriervorrichtung unter Rühren bei Raumtemperatur. Die Wasserstoffaufnahme beträgt anfangs etwa 20 ml je Minute und verzögert sich gegen Ende der Hydrierung sehr stark. Nach 240 ml Wasserstoffaufnahme kommt die Hydrierung völlig zum Stillstand. Example 1 3.0 g of potassium 9-heptadecinate are dissolved in 50 ml of methanol. The solution is in a solution of Raney nickel pre-hydrogenated with hydrogen Methanol added dropwise. After the solution has been completely added dropwise, the hydrogen is taken up in a conventional hydrogenation device with stirring at room temperature. The hydrogen uptake is initially about 20 ml per minute and is delayed towards the end of the hydrogenation very strong. After uptake of 240 ml of hydrogen, the hydrogenation comes to a complete standstill.
Nach dem Verdrängen des über der Lösung stehenden Wasserstoffes durch Stickstoff wird vom Hydrierkatalysator abfiltriert und die Lösung bei 12 Torr zur Trockne eingedampft. Es werden 3,0 g farbloses Kaliumsalz der cis-9-Heptadecensäure erhalten. Nach dem Infrarotspektrum ist die entstandene Verbindung frei von dem entsprechenden trans-Isomeren.After displacing the hydrogen above the solution Nitrogen is filtered off from the hydrogenation catalyst and the solution at 12 Torr for Evaporated to dryness. There are 3.0 g of a colorless potassium salt of cis-9-heptadecenoic acid obtain. According to the infrared spectrum, the resulting compound is free from that corresponding trans isomers.
Beispiel 2 Eine Lösung von 5,0 g 9-Pentadecinsäure in 30 ml Methanol wird mit 1,81 g Morpholin, C4H9NO, versetzt und in eine mit Wasserstoff vorhydrierte Aufschlämmung von Raney-Nickel in Methanol getropft. Example 2 A solution of 5.0 g of 9-pentadecinic acid in 30 ml of methanol 1.81 g of morpholine, C4H9NO, are added and the mixture is pre-hydrogenated with hydrogen Raney nickel slurry in methanol was added dropwise.
Die in einer üblichen Hydriervorrichtung unter Rühren oder Schütteln bei Raumtemperatur und einem Druck von 2 bis 3 at vorgenommene Hydrierung mit Wasserstoff erfolgt anfänglich rasch und wird gegen Ende der Hydrierung immer langsamer. Nach der Aufnahme von 470 ccm Wasserstoff (berechnet auf Normalbedingungen) bleibt die Hydrierung stehen.In a conventional hydrogenation device with stirring or shaking hydrogenation with hydrogen carried out at room temperature and a pressure of 2 to 3 atm takes place quickly at the beginning and becomes slower and slower towards the end of the hydrogenation. To the uptake of 470 ccm of hydrogen (calculated under normal conditions) remains the Stand hydrogenation.
Die Lösung wird vom Katalysator abfiltriert und zur Trockne eingedampft. Man erhält das Morpholinsalz der cis-9-Pentadecensäure in einer Ausbeute von 6,8 g als farbloses Öl, das bei Raumtemperatur nicht erstarrt.The solution is filtered off from the catalyst and evaporated to dryness. The morpholine salt of cis-9-pentadecenoic acid is obtained in a yield of 6.8 g as a colorless oil that does not solidify at room temperature.
Das Infrarotspektrum hat keine Bande bei 962 cm-l, die kennzeichnend für transständige Olefine ist. Die The infrared spectrum has no band at 962 cm-1, which is characteristic of is for trans olefins. the
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEG33786A DE1195296B (en) | 1958-06-28 | 1958-06-28 | Process for the preparation of anti-inflammatory and edema-inhibiting salts of cis-9-pentadecenoic acid and cis-9-heptadecenoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEG33786A DE1195296B (en) | 1958-06-28 | 1958-06-28 | Process for the preparation of anti-inflammatory and edema-inhibiting salts of cis-9-pentadecenoic acid and cis-9-heptadecenoic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1195296B true DE1195296B (en) | 1965-06-24 |
Family
ID=7124777
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEG33786A Pending DE1195296B (en) | 1958-06-28 | 1958-06-28 | Process for the preparation of anti-inflammatory and edema-inhibiting salts of cis-9-pentadecenoic acid and cis-9-heptadecenoic acid |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1195296B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994021247A1 (en) * | 1993-03-25 | 1994-09-29 | Beiersdorf Ag | Use of cis-9-heptadecenoic acid for treating psoriasis, allergies and autoimmune diseases |
| CN115052852A (en) * | 2020-01-29 | 2022-09-13 | 巴利阿里群岛大学 | Alpha-hydroxylated fatty acid metabolites, medical uses thereof, and uses as biomarkers |
-
1958
- 1958-06-28 DE DEG33786A patent/DE1195296B/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994021247A1 (en) * | 1993-03-25 | 1994-09-29 | Beiersdorf Ag | Use of cis-9-heptadecenoic acid for treating psoriasis, allergies and autoimmune diseases |
| DE4309512A1 (en) * | 1993-03-25 | 1994-09-29 | Beiersdorf Ag | Use of cis-9-heptadecenoic acid |
| CN115052852A (en) * | 2020-01-29 | 2022-09-13 | 巴利阿里群岛大学 | Alpha-hydroxylated fatty acid metabolites, medical uses thereof, and uses as biomarkers |
| EP4098649A4 (en) * | 2020-01-29 | 2024-04-17 | Universitat de les Illes Balears | Alpha-hydroxylated fatty-acid metabolites, medical uses of same and use as biomarkers |
| AU2023248158B2 (en) * | 2020-01-29 | 2025-11-27 | Universitat De Les Illes Balears | Alpha-Hydroxylated Fatty-Acid Metabolites, Medical Uses of Same and Use as Biomarkers |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1493579B1 (en) | Process for the preparation of new pharmaceutically valuable compounds | |
| EP0011237A1 (en) | Polyether derivatives, a method for their preparation and their use as pharmaceuticals | |
| DE2203373B2 (en) | NEW 2-SQUARE BRACKETS ON (2- ALKYLBENZOFURAN-3-YL) -METHYL SQUARE BRACKETS FOR -DELTA HIGH 2 -IMIDAZOLINE | |
| DE2522533A1 (en) | 17ALPHA-HYDROXY, 19-NORPREGNA-4,6-DIEN-3, 20-DIONE DERIVATIVES, METHOD FOR THEIR PRODUCTION AND THERAPEUTIC USE | |
| DE2504045B2 (en) | 16.17 DIHYDRO-APOVINCAMIC ACID-2-HYDROXYPROPYLESTER, THEIR SALT, METHOD FOR THEIR MANUFACTURE AND MEDICINAL PRODUCTS | |
| DE1195296B (en) | Process for the preparation of anti-inflammatory and edema-inhibiting salts of cis-9-pentadecenoic acid and cis-9-heptadecenoic acid | |
| DE1468311C3 (en) | 6-chloro-4,6-pregnadiene-3beta-17 alpha-diol-20-one-17-acetate-3-methyl ether and processes for its production and pharmaceutical preparations containing them | |
| DE1926359A1 (en) | oxylcanic acids | |
| DE2508251C2 (en) | Derivatives of indole, processes for their preparation and medicaments containing them | |
| DE959825C (en) | Process for the preparation of 2, 3-dihydro-enzo-1, 3-oxazonen- (4) endocyclically substituted | |
| DE1468517B1 (en) | Oestran series steroids and process for their manufacture | |
| AT237603B (en) | Process for the production of new o-toluidides | |
| DE1147221B (en) | Process for the preparation of anti-inflammatory and anti-edema salts of pentadecenoic and heptadecenoic acids | |
| DE1136326B (en) | Process for the production of 9-heptadecinic acid, 9-pentadecinic acid and their salts with physiologically compatible bases | |
| DE431166C (en) | Process for the preparation of alkamine esters of N-monoalkylated and N-monoalkyloxyalkylated derivatives of p-aminobenzoic acid | |
| DE1303930C2 (en) | 2- (2-CHLORO-4-METHYL- OR-AETHYL- ANILINO) -1,3- DIAZACYCLOPENTEN- (2), THEIR SALTS AND A PROCESS FOR THEIR PRODUCTION | |
| AT333264B (en) | METHOD FOR PREPARING THE NEW 3- (4-BIPHENYLYL) -3-METHYL-PROPIONIC ACID NITRILE | |
| DE2227487C3 (en) | Derivatives of 3-ethoxycarbonyl-S-hydroxy-2-methyl-4-piperazinomethyl-indole, process for their preparation and pharmaceuticals | |
| DE2236005C3 (en) | Dibenzagonal bracket on d, square bracket for -dioxepin- square bracket for 1.3 square bracket for -derivatives and their pharmacologically acceptable salts, as well as processes for their production and pharmaceuticals containing them | |
| AT248417B (en) | Process for the preparation of new substituted hydrazine compounds and their salts | |
| DE1493579C (en) | Process for the production of new pharmaceutically valuable compounds | |
| DE1468517C (en) | Ostran series steroids and processes for their manufacture | |
| AT270890B (en) | Process for the preparation of new nitrogen-containing cholestane derivatives which are saturated or unsaturated in the 5 (6) -position and of their acid addition salts | |
| DE1493530C3 (en) | N, N-dimethyl-beta- (p-bromanilino> propionamide and process for making the same | |
| DE1468681C3 (en) | 17beta-tetrahydropyranyloxy compounds of the androstane series as well as processes for their production and remedies |