JPH03193731A - 腫瘍細胞増殖抑制剤 - Google Patents
腫瘍細胞増殖抑制剤Info
- Publication number
- JPH03193731A JPH03193731A JP1332870A JP33287089A JPH03193731A JP H03193731 A JPH03193731 A JP H03193731A JP 1332870 A JP1332870 A JP 1332870A JP 33287089 A JP33287089 A JP 33287089A JP H03193731 A JPH03193731 A JP H03193731A
- Authority
- JP
- Japan
- Prior art keywords
- tumor cell
- acid
- cell proliferation
- oligopeptide
- residue
- 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.)
- Granted
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 13
- 210000004881 tumor cell Anatomy 0.000 title claims abstract description 12
- 230000004663 cell proliferation Effects 0.000 title claims abstract description 10
- 102000015636 Oligopeptides Human genes 0.000 claims abstract description 12
- 108010038807 Oligopeptides Proteins 0.000 claims abstract description 12
- 229940061720 alpha hydroxy acid Drugs 0.000 claims abstract description 11
- 150000001280 alpha hydroxy acids Chemical class 0.000 claims abstract description 11
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical group OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims abstract description 10
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 claims abstract description 10
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229920000642 polymer Polymers 0.000 claims abstract description 8
- 239000003381 stabilizer Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 150000005846 sugar alcohols Chemical class 0.000 claims abstract description 4
- 230000000379 polymerizing effect Effects 0.000 claims abstract description 3
- 239000002184 metal Chemical class 0.000 claims description 4
- 229910052751 metal Chemical class 0.000 claims description 4
- 230000004565 tumor cell growth Effects 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 239000003966 growth inhibitor Substances 0.000 claims description 3
- 238000006116 polymerization reaction Methods 0.000 claims description 3
- 125000000539 amino acid group Chemical group 0.000 claims description 2
- 150000001261 hydroxy acids Chemical class 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 150000001413 amino acids Chemical class 0.000 abstract 1
- 150000001720 carbohydrates Chemical class 0.000 abstract 1
- 239000000470 constituent Substances 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910001868 water Inorganic materials 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 231100000820 toxicity test Toxicity 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- KVZLHPXEUGJPAH-UHFFFAOYSA-N 2-oxidanylpropanoic acid Chemical compound CC(O)C(O)=O.CC(O)C(O)=O KVZLHPXEUGJPAH-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- AMSYHJPIGRMDAI-UHFFFAOYSA-K gold(3+) 2-hydroxypropanoate Chemical compound [Au+3].CC(O)C([O-])=O.CC(O)C([O-])=O.CC(O)C([O-])=O AMSYHJPIGRMDAI-UHFFFAOYSA-K 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
め要約のデータは記録されません。
Description
。
るにもかかわらず、現在使用されているものは、有効で
副作用がなく、安心して使用できるものは皆無である。
法がない現状から一日も早く満足できる抗癌剤の開発が
望まれている。
殖には全く影響せず、ヌードマウスに移植した無性腫瘍
細胞の増殖抑制実験においては、投与開始数日で増殖が
停止し、その後の投与なしにもかかわらず腫瘍が有意に
縮小化し、また、皮下投与によって安定に有効性を示し
、生体において安定な持続性をもつ腫瘍細胞増殖抑制剤
を提供することを目的とするものである。
合物及び重合物、ピログルタミン酸を少なくとも1残基
服務オリゴペプチド及び安定化剤よりなる。
して、α−ヒドロキシ酸が2〜10分子縮合、及び、重
合した化合物及びその金属塩よりなるものである。
オリゴペプチドは、2〜8残基のアミノ酸から成るオリ
ゴペプチドで、ピログルタミン酸が少なくとも1残基含
まれる化合物及びその金属塩よりなるものである。
縮合物及び重合物…10、ピログルタミン酸を少なくと
も1残基含むオリゴペプチド…1〜4、安定化剤(糖、
糖アルコール)…1〜3よりなるものである。
び重合物)の製法 乳酸(α−ヒドロキシプロピオン酸)は化学反応性が大
きく140℃で100分間加熱すると固化する。これを
水に溶かしアルカリ性にすると沈殿が生成し、酸性にし
ても容易に溶けない。175℃で2時間加熱すると水に
は溶けず、メタノールに溶ける物質になる。ここで必要
なのは水溶性で安定であることで、その条件を満たす製
法を以下に記す。
、2時間還流するか120℃〜160℃で100分加熱
する。
溶かし、これにトルエン150m1を加え140℃〜1
60℃で2時間加熱する。
ンゼン100 mlを加え140℃で3〜6時間加熱す
る。
)0.2g及びトルエン150 mlを加え2〜4時間
還流する。
合及び重合した化合物を得る。
の低縮合物及び重合物とピログルタミン酸を少なくとも
1残基含むオリゴペプチドと糖または糖アルコールより
なる安定化剤とを夫々10:1〜4:1〜3の重量比で
混合し、さらに触媒としてα−ヒドロキシプロピオン酸
の金続塩を少量加えて腫瘍細胞増殖抑制剤を作製する。
プラスチック24穴マルチプレートに、10%牛脂児血
清を添加した市販合成培地イーグルMEN990μ!に
各種投与量を含む抑制剤10μlを加えたものを培地と
して加え、37℃で72時間、Co2雰囲気中で培養後
、メチレンブルー色素の細胞への取り組み量を波長20
nmにおける吸光度で測定した。
投与量の関係を次表及び図に示す。
♀ 5週令)の背側部に子宮 頚癌由来株化細胞He1aS−3細 胞1×107個を移植し、移植後5 日目より、実験群には抑制剤を20 mg10.5ml H2Oを1日1回計1o回連続投
与し、対照群には生理 的食塩水0.5mlを同様に投与した。
下に示す。
計2o回投与した場合の対照群と実験群各5例の腫瘍重
量を示す。
細胞を用いて (A) と同様な実験を行なった。
量誘導体であって、正常細胞を用いた毒性試験において
、その増殖には全く影響しない。
実験においては、投与開始数日で増殖が停止し、その後
の投与なしにもかかわらず腫瘍は有意に縮小化した。ま
た、水剤は皮下投与によって安定的に有効性を示すこと
から、生体において安定な持続性をもつ物質である。従
って、動物実験の過程において何ら副作用も観察されず
、水剤は、有効かつ安心して使用可能な抗癌剤として適
したものである。
単分子であると動物に炎症を生じ、10分子を超えると
水に不溶となって使用困難となる。
率の関係を示す線図である。 抑制剤投与量(m9) 手 続 補 正 書 平成3年3月19日
Claims (4)
- (1)α−ヒドロキシ酸の低縮合物及び重合物、ピログ
ルタミン酸を少なくとも1残基含むオリゴペプチド及び
安定化剤よりなる腫瘍細胞増殖抑制剤。 - (2)請求項(1)において、α−ヒドロキシ酸の低縮
合及び重合物が主としてα−ヒドロキシ酸を2〜10分
子縮合、及び重合した化合物及びその金属塩よりなる腫
瘍細胞増殖抑制剤。 - (3)請求項(1)において、ピログルタミン酸を少な
くとも1残基含むオリゴペプチドが2〜8残基のアミノ
酸から成るオリゴペプチドで、ピログルタミン酸が少な
くとも1残基含まれる化合物及びその金属塩よりなる腫
瘍細胞増殖抑制剤。 - (4)請求項(1)において、その重量構成成分比がα
−ヒドロキシ酸の低縮合物及び重合物…10、ピログル
タミン酸を少なくとも1残基含むオリゴペプチド…1〜
4、安定化剤 (糖、糖アルコール)…1〜3である腫瘍細胞増殖抑制
剤。
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1332870A JP2997488B2 (ja) | 1989-12-25 | 1989-12-25 | 腫瘍細胞増殖抑制剤 |
CA002044621A CA2044621A1 (en) | 1989-12-25 | 1990-12-21 | Inhibiting agent against the proliferation of tumour cells |
US07/700,158 US5972879A (en) | 1989-12-25 | 1990-12-21 | Inhibiting agent against the proliferation of tumor cells |
PCT/JP1990/001678 WO1991009612A1 (fr) | 1989-12-25 | 1990-12-21 | Inhibiteur de croissance de cellules tumorales |
KR1019910700779A KR920700671A (ko) | 1989-12-25 | 1990-12-21 | 종양세포 증식 억제제 |
DE69032158T DE69032158T2 (de) | 1989-12-25 | 1990-12-21 | Wachstumsinhibitor von tumorzellen |
DK91900944.9T DK0460232T3 (da) | 1989-12-25 | 1990-12-21 | Tumorcellevækstinhibitor |
AU69127/91A AU635802B2 (en) | 1989-12-25 | 1990-12-21 | Tumor cell growth inhibitor |
AT91900944T ATE164075T1 (de) | 1989-12-25 | 1990-12-21 | Wachstumsinhibitor von tumorzellen |
EP91900944A EP0460232B1 (en) | 1989-12-25 | 1990-12-21 | Tumor cell growth inhibitor |
ES91900944T ES2113370T3 (es) | 1989-12-25 | 1990-12-21 | Agente inhibidor de la proliferacion de celulas tumorales. |
NO913322A NO913322D0 (no) | 1989-12-25 | 1991-08-23 | Inhiberingsmiddel mot proliferasjon av tumorceller. |
SU915010005A RU2034564C1 (ru) | 1989-12-25 | 1991-08-23 | Способ получения ингибитора пролиферации опухолевых клеток |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1332870A JP2997488B2 (ja) | 1989-12-25 | 1989-12-25 | 腫瘍細胞増殖抑制剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH03193731A true JPH03193731A (ja) | 1991-08-23 |
JP2997488B2 JP2997488B2 (ja) | 2000-01-11 |
Family
ID=18259725
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP1332870A Expired - Fee Related JP2997488B2 (ja) | 1989-12-25 | 1989-12-25 | 腫瘍細胞増殖抑制剤 |
Country Status (13)
Country | Link |
---|---|
US (1) | US5972879A (ja) |
EP (1) | EP0460232B1 (ja) |
JP (1) | JP2997488B2 (ja) |
KR (1) | KR920700671A (ja) |
AT (1) | ATE164075T1 (ja) |
AU (1) | AU635802B2 (ja) |
CA (1) | CA2044621A1 (ja) |
DE (1) | DE69032158T2 (ja) |
DK (1) | DK0460232T3 (ja) |
ES (1) | ES2113370T3 (ja) |
NO (1) | NO913322D0 (ja) |
RU (1) | RU2034564C1 (ja) |
WO (1) | WO1991009612A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6825314B1 (en) | 1999-09-20 | 2004-11-30 | Amato Pharmaceutical Products, Ltd. | Process for the preparation of cyclic lactic acid oligomers |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002275256A (ja) * | 2001-03-19 | 2002-09-25 | Tendou Seiyaku Kk | 乳酸オリゴマーの製造方法 |
RU2283654C1 (ru) * | 2005-03-30 | 2006-09-20 | Борис Владимирович Афанасьев | Способ получения ростовых факторов белковой природы, ростовой фактор белковой природы и ингибитор пролиферации фибробластов |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4211769A (en) * | 1977-08-24 | 1980-07-08 | Takeda Chemical Industries, Ltd. | Preparations for vaginal administration |
EP0115472A3 (de) * | 1983-01-27 | 1985-10-02 | Ciba-Geigy Ag | Pyrrolidinonderivate und Verfahren zu ihrer Herstellung |
EP0115473A3 (de) * | 1983-01-27 | 1987-01-21 | Ciba-Geigy Ag | Substituierte Pyrrolidinonderivate und Verfahren zu ihrer Herstellung |
EP0127426A1 (en) * | 1983-05-23 | 1984-12-05 | Takeda Chemical Industries, Ltd. | Percutaneous pharmaceutical compositions for external use |
JPS6023326A (ja) * | 1983-07-18 | 1985-02-05 | Takeda Chem Ind Ltd | ペプチド含有経口投与製剤 |
DE3428372A1 (de) * | 1984-08-01 | 1986-02-13 | Hoechst Ag, 6230 Frankfurt | Mikrokapseln von regulatorischen peptiden mit kontrollierter freisetzung, verfahren zu ihrer herstellung und injektionszubereitungen |
JPS6163613A (ja) * | 1984-09-04 | 1986-04-01 | Mitsui Toatsu Chem Inc | 顆粒状に調整された徐放性製剤 |
-
1989
- 1989-12-25 JP JP1332870A patent/JP2997488B2/ja not_active Expired - Fee Related
-
1990
- 1990-12-21 WO PCT/JP1990/001678 patent/WO1991009612A1/ja active IP Right Grant
- 1990-12-21 AU AU69127/91A patent/AU635802B2/en not_active Ceased
- 1990-12-21 CA CA002044621A patent/CA2044621A1/en not_active Abandoned
- 1990-12-21 KR KR1019910700779A patent/KR920700671A/ko not_active Application Discontinuation
- 1990-12-21 DK DK91900944.9T patent/DK0460232T3/da active
- 1990-12-21 DE DE69032158T patent/DE69032158T2/de not_active Expired - Fee Related
- 1990-12-21 AT AT91900944T patent/ATE164075T1/de not_active IP Right Cessation
- 1990-12-21 ES ES91900944T patent/ES2113370T3/es not_active Expired - Lifetime
- 1990-12-21 EP EP91900944A patent/EP0460232B1/en not_active Expired - Lifetime
- 1990-12-21 US US07/700,158 patent/US5972879A/en not_active Expired - Fee Related
-
1991
- 1991-08-23 NO NO913322A patent/NO913322D0/no unknown
- 1991-08-23 RU SU915010005A patent/RU2034564C1/ru not_active IP Right Cessation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6825314B1 (en) | 1999-09-20 | 2004-11-30 | Amato Pharmaceutical Products, Ltd. | Process for the preparation of cyclic lactic acid oligomers |
Also Published As
Publication number | Publication date |
---|---|
NO913322L (no) | 1991-08-23 |
AU6912791A (en) | 1991-07-24 |
AU635802B2 (en) | 1993-04-01 |
RU2034564C1 (ru) | 1995-05-10 |
CA2044621A1 (en) | 1991-06-26 |
DE69032158D1 (de) | 1998-04-23 |
US5972879A (en) | 1999-10-26 |
ATE164075T1 (de) | 1998-04-15 |
WO1991009612A1 (fr) | 1991-07-11 |
DE69032158T2 (de) | 1998-08-06 |
NO913322D0 (no) | 1991-08-23 |
KR920700671A (ko) | 1992-08-10 |
EP0460232A4 (en) | 1993-03-17 |
DK0460232T3 (da) | 1998-04-14 |
JP2997488B2 (ja) | 2000-01-11 |
ES2113370T3 (es) | 1998-05-01 |
EP0460232A1 (en) | 1991-12-11 |
EP0460232B1 (en) | 1998-03-18 |
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