KR920009774A - S(+) 페닐 알칸산 및 α－아미노산을 함유한 착물 - Google Patents
S(+) 페닐 알칸산 및 α－아미노산을 함유한 착물 Download PDFInfo
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- KR920009774A KR920009774A KR1019910020368A KR910020368A KR920009774A KR 920009774 A KR920009774 A KR 920009774A KR 1019910020368 A KR1019910020368 A KR 1019910020368A KR 910020368 A KR910020368 A KR 910020368A KR 920009774 A KR920009774 A KR 920009774A
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- amino acid
- phenyl
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- -1 (+) phenyl Chemical group 0.000 title claims 14
- 239000002253 acid Substances 0.000 title claims 12
- 235000008206 alpha-amino acids Nutrition 0.000 title claims 11
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 title claims 10
- 239000013543 active substance Substances 0.000 claims 8
- 239000000243 solution Substances 0.000 claims 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 6
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 5
- HEFNNWSXXWATRW-JTQLQIEISA-N dexibuprofen Chemical compound CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1 HEFNNWSXXWATRW-JTQLQIEISA-N 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- 239000011149 active material Substances 0.000 claims 3
- 239000004305 biphenyl Substances 0.000 claims 3
- 239000011521 glass Substances 0.000 claims 3
- 239000008177 pharmaceutical agent Substances 0.000 claims 3
- 238000003756 stirring Methods 0.000 claims 3
- 150000007650 D alpha amino acids Chemical class 0.000 claims 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 2
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 229940024606 amino acid Drugs 0.000 claims 2
- 230000000202 analgesic effect Effects 0.000 claims 2
- 230000000844 anti-bacterial effect Effects 0.000 claims 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims 2
- 230000001754 anti-pyretic effect Effects 0.000 claims 2
- 239000002221 antipyretic Substances 0.000 claims 2
- 239000007864 aqueous solution Substances 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 229960001680 ibuprofen Drugs 0.000 claims 2
- 229960002009 naproxen Drugs 0.000 claims 2
- 239000002244 precipitate Substances 0.000 claims 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims 1
- AHLPHDHHMVZTML-SCSAIBSYSA-N D-Ornithine Chemical compound NCCC[C@@H](N)C(O)=O AHLPHDHHMVZTML-SCSAIBSYSA-N 0.000 claims 1
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 claims 1
- 229930028154 D-arginine Natural products 0.000 claims 1
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 claims 1
- 229930195721 D-histidine Natural products 0.000 claims 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims 1
- 239000004473 Threonine Substances 0.000 claims 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 150000001371 alpha-amino acids Chemical class 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 239000012736 aqueous medium Substances 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 235000009582 asparagine Nutrition 0.000 claims 1
- 229960001230 asparagine Drugs 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 125000006267 biphenyl group Chemical group 0.000 claims 1
- 230000036760 body temperature Effects 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 claims 1
- 238000007710 freezing Methods 0.000 claims 1
- 230000008014 freezing Effects 0.000 claims 1
- 235000013922 glutamic acid Nutrition 0.000 claims 1
- 239000004220 glutamic acid Substances 0.000 claims 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 229960000310 isoleucine Drugs 0.000 claims 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims 1
- 229960003136 leucine Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 239000000155 melt Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
- 239000012452 mother liquor Substances 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 230000003204 osmotic effect Effects 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 1
- 125000003367 polycyclic group Chemical group 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 239000005518 polymer electrolyte Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 239000007921 spray Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 239000004474 valine Substances 0.000 claims 1
- 229960004295 valine Drugs 0.000 claims 1
- 238000012982 x-ray structure analysis Methods 0.000 description 2
- IHHXIUAEPKVVII-QDXATWJZSA-N (2r)-2,6-diaminohexanoic acid;2-[4-(2-methylpropyl)phenyl]propanoic acid Chemical compound NCCCC[C@@H](N)C(O)=O.CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 IHHXIUAEPKVVII-QDXATWJZSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Communicable Diseases (AREA)
- Rheumatology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
내용 없음.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 본 발명에 따른 착물에 대한 X－선 구조 분석결과를 개략적으로 도시한 도면,
제2도 X－선 구조 분석에 의하여 이부프로펜－α－아미노산 착물에 대한 결정구조를 개략적으로 도시한 도면,
제3도는 S(+)－이부프로펜－D－리시네이트 투여후 플라즈마 수준 곡선을 도시한 그래프.
Claims (16)
- 착물결합이 R1－COOH가 S(+)－페닐 알칸산을 의미하고 R2－COOH가 염기성 α－아미노산을 의미하는 형태 R1－COOH···－OOC－R2 R1－COO－···HOOC－R2의 양성자 스위치로서 카르복실레이트－카르복실 상호작용을 기초로하여 S(+)－페닐 알칸산의 카르복실기에 관한 pKa치가 3.5－3.9이며 염기성 α－아미노산의 카르복실기에 관한 pKa치가 1.9－2.9인 S(+)－페닐 알칸산과 염기성 α－아미노산으로 이루어진 화학양론 1 : 1의 수소다리－결합착물.
- 제1항에 있어서, 염기성 α－아미노산의 카르복실기에 관한 pKa치가 1.9－2.2인 것이 특징인 착물.
- 제1 또는 2항에 있어서, S(+)－페닐 알칸산으로서 S(+)－이부프로펜 또는 S(+)－나프록센이 사용되는 것이 특징인 착물.
- 전항중의 어느 한 항에 있어서, 염기성 α－아미노산의 D형태가 사용되는 것이 특징인 착물.
- 전항중의 어느 한 항에 있어서, α－아미노산이 다음 일반식을 가진 것이 특징인 착물 :상기 식에서 X=NH2, NHCH3, NHC2H5, C1－C6알칸일 아미노 Z=H, OH, NH2, A= 결합 또는 탄소원자수 1－10개 및 필요하다면 아미노기 또는 1－6개의 히드록실기를 함유한 알킬렌 사슬.
- 전항중의 어느 한항에 있어서, 염기성 D－α－아미노산으로서 D－리신, D－아르기닌, D－히스티딘 또는 D－오르니틴이 사용되는 것이 특징인 착물.
- 전항중의 어느 한항에 있어서, 착물이 발린, 로이신, 이소로이신, 아스파라긴산, 글루타민산, 아스파라긴, 글루타민, 페닐알라닌, 세린, 트레오닌 또는 히드록시리신을 함유한 것이 특징인 착물.
- 다음 단계의 방법을 특징으로 하는 전항중의 어느 한항에 따른 착물의 제조방법. a) 수성매질(단지 물) 또는 pH 5.5－7.5(20℃) 범위에 포함되는 약한 완충 수용액으로 부터 제조를 위하여 완충 수용액, 예를들어 0.01M－0.001M－K2HPO4/KH2PO4완충액 pH 6.0－7.5(20℃)을 제조하고 그것에 동량의 S(+)－페닐 알칸산을 일정 교반하에 도입시키고; b) 일정 교반하게 깨끗한 투명 용액이 얻어지고(보통 20분 후) 모든 S(+)－페닐 알칸산이 용액으로 될 때까지 용액을 40℃로 가열하며; c) 그후 묽은 인산(H3PO4)(20℃)의 첨가에 의하여 pH5.5－6.0으로 용액의 pH를 조절한다음 일정 교반하에 α－아미노산의 동일량(상응하는 양)을 도입시켜 중성 α－아미노산이 도입되어 염산(HCl)－α－아미노산이 도입되지 않도록 확인하며; d) 20분후 착물 형성이 종료되며 그때 0－4℃로 냉각후 착물이 결정형태로 침전하고 소결된 유리 깔때기 또는 유리필터(1G4)에 의하여 모액으로 부터 분리할 수 있고; e) 방법 단계 d)와 별도로 깨끗한 용액을 물분사 진공내 회전식 증발기(수조온도 25－30℃)에서 그 부피의 반으로 감소시킬 수 있고, 이때 1G4 유리필터에 의하여 여과되며 물/에탄올(70/30/v/v) 또는 에틸 아세테이트(100%)로 부터 재결정화될 수 있는 무색(비정질)침전물을 형성시킨다.
- 전항중의 어느 한항에 따른 착물 한가지 또는 그이상 및 가능하게는 임의로 추가의 생리적으로 양립가능한 중량제 또는 담체를 함유한 약제제.
- 제9항에 있어서, 항염증, 해열, 항균 및 진통효과를 가진 페닐 알칸산을 기재로 하고, 페닐 알칸산과 α－아미노산으로 이루어진 활성물질 착물 및 가능하게는 추가의 통상 생리적으로 양립가능한 보조물질을 함유하고, 활성물질 착물이 S(+)－페닐 알칸산과 염기성 α－아미노산, 바람직하게는 D－α－아미노산으로 구성된 것이 특징인 약제제.
- 제9 또는 10항에 있어서, 항염증, 해열, 항균 및 진통효과를 가진 이부프로펜 또는 나프록센을 기재로 하고, 이부프로펜 또는 나프록센 및 염기성 α－아미노산 및 가능하게는 추가의 통상 생리적으로 양립가능한 보조물질을 함유하며, 활성물질 착물이 S(+)－이부프로펜 또는 S(+)－나프록센 및 염기성 α－아미노산으로 이루어지고 조성중 0.1－90 중량%(w/w)의 양을 나타내는 것이 특징인 약제제.
- 제9－11항중 어느 한 항에 있어서, S(+)－이부프로펜 또는 S(+)－나프록센 50－800mg, 바람직하게는 100－600mg, 특히 100－300mg을 함유한 것이 특징인 약제제.
- 제9－12항중 어느 한 항에 있어서, 한가지 또는 그 이상의 활성물질 착물과 20－80℃에서 고체화하고 수용성인 수용성 담체, 특히 폴리에틸렌 글리콜로 구성되고, 등방용액이며, a) 활성물질이 일분자형태 또는 이온으로서 일분자 형태로 용해되며, b) 활성 물질이 그의 본래 형태 및/또는 생물학적으로 활성인 키랄(에난시오머) 형태로 존재하며, c) 활성물질이 37℃에서 0.001－0.67의 몰분율을 가지고, d) 담체가 체온에서 용융되고, 상균일 및 등방성이 있으며, e) 담체가 활성물질로 구성된 등방용액이 상온에서 고체화하며, f) 고체화 물질이 결정 또는 비결정질이고 결정형태로 활성물질을 함유하거나 또는 활성물질을 결정화할 수 있고, g) 일분자 또는 이온용액이 삼투압을 가지며 몰 빙점강하 효과가 있고, h) 중합체 전해질내 용해된 활성물질이 온도의존 확산계수 및 온도의존 비전도도를 가진 것이 특징인 약제제.
- 제9－13항중 어느 한 항에 있어서, 경구 또는 비경구 투여에 적합한 투여량이 S(+)－이부프로펜 1일 50－1200mg, 보통 1일 100－800mg, 바람직하게는 1일 200－600mg이며 착물의 국부투여에 적합한 투여량이 1일 10－200mg인 것이 특징인 약제제.
- 전항중의 어느 한항에 있어서, S(+)－페닐 알칸산이 다음 일반식을 가진 것이 특징인 착물.상기 식에서 R은 저급알킬이고, Ar은 방향족계에서 탄소원자 12개까지 함유한 모노시클릭, 폴리시클릭 또는 오르토 축합 폴리 시클릭 방향족기, 이를테면 페닐, 디페닐, 및 나프틸이고, 이들 방향족기의 치환체가 한가지 또는 그 이상의 할로겐원자, C1－C4－알킬, 벤질, 히드록시, C1－C2－알콕시, 페녹시 및 벤조일기로 이루어진다.
- 제15항에 있어서, 치환된 아릴이 4－이소부틸－페닐, 3－페녹시－페닐, 2－플루오로－4－디페닐, 4′－플루오로－4－디페닐, 6－메톡시－2－나프틸, 5－클로로－6－메톡시－2－니프틸 및 5－브로모－6－메톡시－나프틸, 4－클로로－페닐, 4－디플로오로－메톡시－페닐, 6－히드록시－2－나프틸, 및 5－브로모－6－히드록시－2－나프틸인 것이 특징인 착물.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4036458 | 1990-11-15 | ||
| DEP4036458.5 | 1990-11-15 |
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| KR920009774A true KR920009774A (ko) | 1992-06-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1019910020368A KR920009774A (ko) | 1990-11-15 | 1991-11-15 | S(+) 페닐 알칸산 및 α－아미노산을 함유한 착물 |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0486045B1 (ko) |
| JP (1) | JPH0656737A (ko) |
| KR (1) | KR920009774A (ko) |
| CN (1) | CN1061404A (ko) |
| AT (1) | ATE137733T1 (ko) |
| AU (1) | AU8790591A (ko) |
| BR (1) | BR9104996A (ko) |
| CA (1) | CA2055683A1 (ko) |
| CS (1) | CS346491A3 (ko) |
| DE (2) | DE4137675A1 (ko) |
| HU (1) | HUT59656A (ko) |
| MX (1) | MX9102088A (ko) |
| NZ (1) | NZ240617A (ko) |
| PL (1) | PL292413A1 (ko) |
| ZA (1) | ZA919077B (ko) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| HUT59692A (en) * | 1990-11-15 | 1992-06-29 | Puetter Medice Chem Pharm | Process for producing complexes containing s/+/-phenyl-alkanoic acids and aminosugars |
| HUT59653A (en) * | 1990-11-15 | 1992-06-29 | Puetter Medice Chem Pharm | Process for producing complexes containing s/+/-phenyl-alcanoic acids and alpha-hydroxy-alcanoic acids and pharmaceutical compositions containing them as active components |
| CA2108041A1 (en) * | 1991-03-29 | 1992-09-30 | Nicholas S. Bodor | Targeted drug delivery via mixed phosphate derivatives |
| US5599969A (en) * | 1992-12-02 | 1997-02-04 | The Boots Company Plc | Process of resolving phenylpropionic acids using α-methylbenzylamine |
| IT1272149B (it) * | 1993-03-26 | 1997-06-11 | Zambon Spa | Composizione farmeceutiche ad attivita' analgesica |
| IT1264855B1 (it) * | 1993-06-21 | 1996-10-17 | Zambon Spa | Composizioni farmaceutiche contenenti sali dell'acido s(+)-2-(4-isobutilfenil) propionico con amminoacidi basici |
| ES2221385T3 (es) * | 1998-05-15 | 2004-12-16 | Warner-Lambert Company Llc | Preparaciones de gabapentina y pregabalina estabilizadas con aminoacidos y procedimiento para prepararlas. |
| AR057882A1 (es) | 2005-11-09 | 2007-12-26 | Novartis Ag | Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra |
| CN101455653B (zh) * | 2007-12-13 | 2013-03-06 | 天津医科大学 | 精氨酸布洛芬口腔崩解片及其制备方法 |
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| GB1497044A (en) * | 1974-03-07 | 1978-01-05 | Prodotti Antibiotici Spa | Salts of phenyl-alkanoic acids |
| ATE50493T1 (de) * | 1986-11-14 | 1990-03-15 | Puetter Medice Chem Pharm | Ibuprofen enthaltendes arzneimittel. |
| DK0424028T3 (da) * | 1989-10-17 | 1996-01-29 | Merck & Co Inc | S(+)-ibuprofen-L-aminosyre og S(+)-ibuprofen-D-aminosyre som et forbedret smertestillende middel med fremskyndet indtrædelse |
-
1991
- 1991-11-14 HU HU913571A patent/HUT59656A/hu unknown
- 1991-11-15 CS CS913464A patent/CS346491A3/cs unknown
- 1991-11-15 KR KR1019910020368A patent/KR920009774A/ko not_active Application Discontinuation
- 1991-11-15 CN CN91110739A patent/CN1061404A/zh active Pending
- 1991-11-15 AU AU87905/91A patent/AU8790591A/en not_active Abandoned
- 1991-11-15 AT AT91119522T patent/ATE137733T1/de not_active IP Right Cessation
- 1991-11-15 NZ NZ240617A patent/NZ240617A/en unknown
- 1991-11-15 MX MX9102088A patent/MX9102088A/es unknown
- 1991-11-15 JP JP3354099A patent/JPH0656737A/ja active Pending
- 1991-11-15 CA CA002055683A patent/CA2055683A1/en not_active Abandoned
- 1991-11-15 DE DE4137675A patent/DE4137675A1/de not_active Withdrawn
- 1991-11-15 ZA ZA919077A patent/ZA919077B/xx unknown
- 1991-11-15 EP EP91119522A patent/EP0486045B1/de not_active Revoked
- 1991-11-15 PL PL29241391A patent/PL292413A1/xx unknown
- 1991-11-15 DE DE59107790T patent/DE59107790D1/de not_active Revoked
- 1991-11-18 BR BR919104996A patent/BR9104996A/pt not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0486045A3 (en) | 1992-12-09 |
| CS346491A3 (en) | 1992-06-17 |
| AU8790591A (en) | 1992-05-21 |
| CA2055683A1 (en) | 1992-05-16 |
| JPH0656737A (ja) | 1994-03-01 |
| HUT59656A (en) | 1992-06-29 |
| NZ240617A (en) | 1994-12-22 |
| DE4137675A1 (de) | 1992-05-21 |
| EP0486045B1 (de) | 1996-05-08 |
| MX9102088A (es) | 1993-01-01 |
| EP0486045A2 (de) | 1992-05-20 |
| ATE137733T1 (de) | 1996-05-15 |
| PL292413A1 (en) | 1993-01-25 |
| ZA919077B (en) | 1992-08-26 |
| CN1061404A (zh) | 1992-05-27 |
| BR9104996A (pt) | 1992-06-23 |
| HU913571D0 (en) | 1992-01-28 |
| DE59107790D1 (de) | 1996-06-13 |
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