JPH0723309B2 - Cancer treatment - Google Patents
Cancer treatmentInfo
- Publication number
- JPH0723309B2 JPH0723309B2 JP24642585A JP24642585A JPH0723309B2 JP H0723309 B2 JPH0723309 B2 JP H0723309B2 JP 24642585 A JP24642585 A JP 24642585A JP 24642585 A JP24642585 A JP 24642585A JP H0723309 B2 JPH0723309 B2 JP H0723309B2
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- Prior art keywords
- proline
- hydroxy
- cis
- cells
- tumor
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Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、癌、特に悪性上皮性腫瘍および関連の腫瘍に
対する治療薬剤、ならびにそれを用いる新治療法に関す
る。TECHNICAL FIELD The present invention relates to a therapeutic agent for cancer, particularly malignant epithelial tumor and related tumors, and a new therapeutic method using the same.
「関連の腫瘍」という表現も、腫瘍を意味し、上皮の発
生部位を同じくする悪性上皮性腫瘍のことである。例え
ば、神経膠星状細胞腫、神経鞘腫、副腎（髄質）腫瘍な
どである。The expression "related tumor" also means a tumor, which is a malignant epithelial tumor that shares the same site of epithelial development. For example, astrocytomas, schwannomas, adrenal (medullary) tumors and the like.
1933年から1946年の間、米国国立癌研究所（United St
ates National Cancer institute）のヘレン．エ
ム．ダイヤー（Helen M.Dyer）は、マウスの実験的腫
瘍に広範囲のアミノ酸を投与した。なかでも、彼女は、
ヒドロキシヒドリンについて述べた。しかし、実験動物
の腫瘍について得られた結果は、人間の癌には殆ど転用
できないことが知られている。Between 1933 and 1946, the National Cancer Institute
Helens of ates National Cancer Institute). M. Helen M. Dyer administered a wide range of amino acids to experimental tumors in mice. Among them, she
Hydroxyhydrin was mentioned. However, it is known that the results obtained for tumors of experimental animals can hardly be transferred to human cancer.
最近の約20年に、電子顕微鏡により、細胞内における細
胞体質の存在が確認されている。今日、細胞体質を応用
する発生学的方法が、よく使われ、転移面における癌の
発生を知ることができる。In the last 20 years, the presence of cytoplasm in cells has been confirmed by electron microscopy. Today, embryological methods that apply the cytoplasm are often used to find out the occurrence of cancer in the metastatic plane.
しかし、本出願人の考えを押し進めれば、細胞体質の障
害は、癌、特に悪性上皮性腫瘍の発病に関し重要な要因
であると言える。癌の細胞や組織において、細胞体質、
細胞接合部、基底板および細胞外質のフィラメント、そ
れに、結合組織が狂っていると、間違いなく、特定のア
ミノ酸であるこれらのフィラメント組織の成分の置換が
現われる。However, if the applicant's idea is pushed forward, it can be said that the disorder of the cytoplasm is an important factor in the onset of cancer, particularly malignant epithelial tumor. In cancer cells and tissues, the cytoplasm,
Derangements of cell junctions, basal lamina and extracellular filaments, as well as connective tissue, undoubtedly result in the substitution of certain filamentous components of these filamentous tissues.
このような点から、これらのアミノ酸のうち、最も重要
なものの一つが、ヒドロキシプロリンである。ところ
が、ダイヤー（Dyer）が行なったように、ＬとＤの間の
構造を区別することは不十分である。From this point of view, one of the most important of these amino acids is hydroxyproline. However, it is insufficient to distinguish the structure between L and D, as Dyer did.
極めて重要なことは、炭素原子（この炭素原子の数は、
好ましくは４であるが、３である場合も考えられる。）
を有するヒドロキシル基の非対称性から生ずるヒドロキ
シプロリンのシス型、およびトランス型の異性体におけ
る差異を、はっきりさせることである。Very importantly, carbon atoms (the number of carbon atoms
It is preferably 4, but a case of 3 is also conceivable. )
To clarify the differences in the cis and trans isomers of hydroxyproline resulting from the asymmetry of the hydroxyl group with.
このことの正当性は、本出願人の提案に基づいて行なわ
れたテストによって実証された。このテストは、結果を
人間の癌に殆ど転用することができないような実験動物
の腫瘍に対するテストとは異なるものである。The justification for this was substantiated by tests carried out on the applicant's proposal. This test is different from the test for tumors in laboratory animals, whose results are hardly transferable to human cancer.
シス−４−ヒドロキシ−Ｌ−プロリンは、植物から抽出
により得ることができるが、合成により製造することも
できる。Cis-4-hydroxy-L-proline can be obtained from plants by extraction, but can also be produced synthetically.
シス−４−ヒドロキシ−Ｌ−プロリンの薬物学的報告 シス−４−ヒドロキシ−Ｌ−プロリンは、まったく無害
な物質である。急性毒性は、1000mg/kgより高い。一般
的のみならず、局所的認容性も優れている。経口適用の
際に、これは、胃腸に障害をおよぼさず、静脈適用の際
には、血管に障害をおよぼさない。Pharmacological report of cis-4-hydroxy-L-proline Cis-4-hydroxy-L-proline is a completely harmless substance. Acute toxicity is higher than 1000 mg / kg. Not only general but also local tolerability is excellent. Upon oral application it does not damage the gastrointestinal tract and upon intravenous application it does not damage blood vessels.
実験動物癌は、シス−４−ヒドロキシ−Ｌ−プロリンの
作用立証のためには好適性が低い。従って、シス−４−
ヒドロキシ−Ｌ−プロリンの抗癌作用立証は、細胞培養
で行った。Experimental animal cancers are less suitable for demonstrating the action of cis-4-hydroxy-L-proline. Therefore, cis-4-
Demonstration of the anti-cancer effect of hydroxy-L-proline was carried out in cell culture.
シス−４−ヒドロキシ−Ｌ−プロリン（細胞106個当た
り100ug）を含有する倍地中で培養の際に、ヒト神経膠
星状細胞腫細胞の生長（細胞分裂）は著しく減少され
る。この際、比較物質としてトランス−４−ヒドロキシ
−Ｌ−プロリンを使用した。When cultured in medium containing cis-4-hydroxy-L-proline (100 ug per 10 6 cells), human astrocytoma cell growth (cell division) is significantly reduced. At this time, trans-4-hydroxy-L-proline was used as a comparative substance.
トランス−４−ヒドロキシ−Ｌ−プロリン及び天然異性
体（シス−４−ヒドロキシ−Ｌ−プロリン）の腫瘍細胞
培養物上への作用の比較 この報告は、ヒト神経膠星状細胞結腸の腺癌及びK562細
胞の一次培養物を作り、トランス−４−ヒドロキシ−Ｌ
−プロリン及び天然異性体（シス−４−ヒドロキシ−Ｌ
−プロリン）と共に、時間依存的にインキュベートする
際に起こる形態学的現象に関する。悪性腫瘍細胞の挙動
におけるいくつかの変化、例えば、移動、波打ち（Ruff
ling）及び細胞質分裂は、細胞体質中における変化によ
り追跡できる。Comparison of the effects of trans-4-hydroxy-L-proline and the natural isomer (cis-4-hydroxy-L-proline) on tumor cell cultures This report shows that adenocarcinoma of the human astrocyte colon and Make a primary culture of K562 cells and trans-4-hydroxy-L
-Proline and natural isomers (cis-4-hydroxy-L
-Proline) with respect to the morphological phenomena that occur during the time-dependent incubation. Some changes in the behavior of malignant tumor cells, such as migration, ruffling (Ruff
lings) and cytokinesis can be followed by changes in the cytoplasm.
シス−４−ヒドロキシ−Ｌ−プロリン（細胞106個当た
り100μｇ）を含有する培地中に神経膠星状細胞腫細胞
を接種の後、14〜20日に細胞分裂はかなり減速される。
この細胞をコロニー形成検定用の二層寒天よりなる新し
い培地皿に移すと、トランス−４−ヒドロキシ−Ｌ−プ
ロリンの存在又は試験化合物不存在の場合と比べて、ク
ラスラー及びコロニーの数は著しく減少する。天然異性
体を含有する培地に移すと、神経膠星状細胞腫細胞から
の培養物中で、誘導された腺維芽球及び上皮類似細胞は
生長し始め、長い繊維状の突起に生長し、表面微絨毛及
び動物学的水泡（zootic blebs）の数は著しく減少す
る。これらの現象は、一般に培養物中で５〜７日の間に
培養液物中で観察され、かつ培養物の形態学的態様はニ
ューロン類似細胞上に残る。After inoculation of astrocytoma cells in medium containing cis-4-hydroxy-L-proline (100 μg per 10 6 cells), cell division is significantly slowed 14-20 days later.
Transfer of the cells to a new medium dish consisting of double layer agar for colony formation assay significantly reduced the number of clathlers and colonies compared to the presence of trans-4-hydroxy-L-proline or the absence of test compound. To do. When transferred to medium containing natural isomers, induced fibroblasts and epithelial-like cells began to grow in cultures from astrocytoma cells, growing into long filamentous processes, The number of surface microvilli and zootic blebs is significantly reduced. These phenomena are generally observed in culture for 5-7 days in culture, and the morphological aspects of the culture remain on neuron-like cells.
同数のヒト神経膠星状細胞腫細胞を３種の培地中に接種
した。第１の培地は対照培地であり試験化合物を含有せ
ず、第２の培地にはシス−４−ヒドロキシ−Ｌ−プロリ
ンを加え、第３の培地にはトランス−４−ヒドロキシ−
Ｌ−プロリンを加えて培養した。結果は次の通りであっ
た。Equal numbers of human astrocytoma cells were seeded in the three media. The first medium was the control medium and contained no test compound, cis-4-hydroxy-L-proline was added to the second medium and trans-4-hydroxy- was added to the third medium.
L-proline was added and cultured. The results were as follows.
更に、シス−４−ヒドロキシ−Ｌ−プロリンは、神経膠
星状細胞腫の細胞培養物中で、再分化（Redifferenzier
ung）をもたらし、即ち、細胞は、もはや同じ腫瘍細胞
ではなく、正常な星状細胞である。このような現象は、
シス−４−ヒドロキシ−Ｌ−プロリンと共にインキュベ
ート４日後に現われた。このような再分化は、腎臓癌細
胞においても認められた。 In addition, cis-4-hydroxy-L-proline is redifferentiated (Redifferenzier) in astrocytoma cell cultures.
ung), ie the cells are no longer the same tumor cells but normal astrocytes. Such a phenomenon is
Appeared after 4 days of incubation with cis-4-hydroxy-L-proline. Such redifferentiation was also found in renal cancer cells.
シス−４−ヒドロキシ−Ｌ−プロリン（CHP）の分化作
用 シス−４−ヒドロキシ−Ｌ−プロリンCHP）を、その抗
腫瘍作用に関して試験した。培養物中で、CHPは、多く
のコロニー形成細胞を抑制した。ヒト神経膠星状細胞腫
細胞中で、CHPは、表現型再分化を起こさせ、腺癌（結
腸癌、乳癌、肺癌）中での最もはっきりした効果は、コ
ロニー形成における減少であった。CHPは、細胞核係留
に、細胞体質の介在フィラメント蛋白質のオーダー増加
により影響した。インフォームドコンセントにより、CH
Pを１日当たり１〜10gの用量で腫瘍患者に与えて、毒性
は認められなかった。この処置は、肝臓移転への生長抑
制作用をもたらし、痛みを減少した。Differentiation effect of cis-4-hydroxy-L-proline (CHP) Cis-4-hydroxy-L-proline CHP) was tested for its antitumor effect. In culture, CHP suppressed many colony forming cells. In human astrocytoma cells, CHP underwent phenotypic redifferentiation and the most pronounced effect in adenocarcinomas (colon cancer, breast cancer, lung cancer) was a reduction in colony formation. CHP affected nuclear anchorage by increasing the order of interstitial filament proteins in the cytoplasm. CH with informed consent
P was given to tumor patients at a dose of 1-10 g per day and no toxicity was observed. This treatment had a growth inhibitory effect on liver transfer and reduced pain.
シス−４−ヒドロキシ−Ｌ−プロリンの細胞内作用点を
同様に神経膠星状細胞腫で立証した。抗ケラチン−抗体
の使用は、この細胞体質を細胞核の消失まで破壊する。
しかしながら、同じ実験をシス−４−ヒドロキシ−Ｌ−
プロリンと共にインキュベートして実施すると、細胞体
質障害は、比較できないほど少なく、細胞核は残存す
る。The intracellular site of action of cis-4-hydroxy-L-proline was also demonstrated in astrocytomas. The use of anti-keratin-antibodies destroys this cytoplasm until the disappearance of the cell nucleus.
However, the same experiment was performed with cis-4-hydroxy-L-
When carried out by incubating with proline, cytoplasmic damage was incomparably small and the cell nucleus remained.
腫瘍細胞は高度に凝集する傾向を有する。これに反し
て、シス−４−ヒドロキシ−Ｌ−プロリンと共にインキ
ュベートした腫瘍細胞は、次のように、特に結腸癌細胞
では、凝縮性は正常細胞と同様であった： ヒト赤血白血病細胞系（K562）における幹細胞に対する
作用は、次の通りであった： 臨床治験： シス−４−ヒドロキシ−Ｌ−プロリンは、単一物質とし
て、２病院で臨床的に独占的処置として使用した。19患
者を合計91週間にわたり処置した。局部的に再発及び転
移を伴いその苦痛が極めて進行した結腸癌患者を処理し
た。この処置は、経口又は静脈で行った。適用量：その
週の５日目に経口的に4g、その週の２日目に静脈から6
g。この処置を数か月にわたり続けた。副作用は現われ
ず、特に、毎日の供給を中断せずに１年以上行った場合
に、血液学的及び他の実験値の病理学的変化は、この物
質によっては認められなかった。静脈適用の際の血管障
害はなかった。脱毛、吐き気等は起こらなかった。Tumor cells tend to be highly aggregated. In contrast, tumor cells incubated with cis-4-hydroxy-L-proline were similar in condensability to normal cells as follows, especially in colon cancer cells: The effects on stem cells in the human erythroleukemia cell line (K562) were as follows: Clinical trial: Cis-4-hydroxy-L-proline was used as a single substance and clinically as an exclusive treatment in 2 hospitals. Nineteen patients were treated for a total of 91 weeks. A colon cancer patient with locally advanced recurrence and metastasis, whose distress was extremely advanced, was treated. This treatment was performed orally or intravenously. Dosage: Oral 4g on the 5th day of the week, 6 intravenously on the 2nd day of the week
g. This treatment was continued for several months. No side effects appeared, and no pathological changes in hematological and other experimental values were observed with this substance, especially when carried out for one year or more without interruption of daily supply. There were no vascular disorders upon intravenous application. Hair loss and nausea did not occur.
次の抗腫瘍作用が、患者で認められた：拡大した癌浸透
が根底から手術できなかった場合に、小骨盤中の局所的
再発は自ずから中止した。急進的な肝臓転移は停止さ
れ、「変化なしの安定病状」及び後の退行性変化をもた
らした。重症の腫瘍苦痛は、著しく減少された。この場
合、この物質は、鎮痛剤ではなく、苦痛減少はむしろ周
囲の細胞（組織）への腫瘍圧力の軽減による。The following anti-tumor effects were noted in the patient: The local recurrence in the small pelvis was spontaneously discontinued when extended cancer penetration could not be radically operated on. Radical liver metastases were arrested, resulting in a "steady stable condition" and later degenerative changes. Severe tumor distress was significantly reduced. In this case, the substance is not an analgesic and the reduction in pain is rather due to a reduction in tumor pressure on surrounding cells (tissues).
人間の細胞培養を用いてテストを行なった。その細胞
は、神経外科的に脳腫瘍の患者からとった。The test was performed using human cell culture. The cells were taken neurosurgically from a patient with a brain tumor.
これらの神経膠星状細胞腫の細胞に、Ｌ−４−シス−ヒ
ドロキシプロリンを投与したところ、細胞分裂に可成り
の遅速性がもたらされ、かつ、形態の再分化が誘発され
た。つまり、細胞は、最早や腫瘍状態ではなく、正常の
星状膠細胞そっくりであった。Administration of L-4-cis-hydroxyproline to these astrocytoma cells resulted in a significant slowing of cell division and induced morphological redifferentiation. That is, the cells were more like normal astrocytes, rather than in the tumor state anymore.
また一方、Ｌ−４−ヒドロキシプロリンのトランス型異
性体のほうは、全く見るべき効果を示さなかった。On the other hand, the trans isomer of L-4-hydroxyproline showed no remarkable effect.
ヒドロキシプロリンは、単独で投与するか、または、前
述のフィラメント組織中に生じている他のアミノ酸、例
えば、バリン，アラニン，リジン，ヒドロキシリジン，
グリシン，システイン，およびシスチンのようなもの
と、組み合わせて用いられる。Hydroxyproline may be administered alone or with other amino acids occurring in the filamentous tissue described above, such as valine, alanine, lysine, hydroxylysine,
Used in combination with such things as glycine, cysteine, and cystine.
遊離状態のアミノ酸を投与することは、可能な方法であ
る。しかし、それらの特定の効果も、アミノ酸を含む化
合物を、例えば、アセチル化された状態か、対応するペ
プチドとして投与することにより、生じさせることがで
きる。それは、前述のアミノ酸を、直接的にも、また、
間接的にも投与しうることを意味する。Administering the free amino acid is a possible method. However, their particular effect can also be produced by administering compounds containing amino acids, for example by administration in the acetylated state or as the corresponding peptides. It is possible to directly and directly
It means that it can be administered indirectly.
アミノ酸には、殆んど毒性がなく、従って、前述の化合
物の投与量の範囲は広い。しかし、アミノ酸療法とはい
え、いわゆる禁忌状態は、可能な限りなくすべきであ
る。特に、腎臓病患者の場合には、しかりである。Amino acids are almost non-toxic and, therefore, the dosage range for the aforementioned compounds is broad. However, even with amino acid therapy, so-called contraindications should be eliminated as much as possible. This is especially true for patients with kidney disease.
これらの化合物の治療上の投与の仕方は、基本的に、あ
らゆるアミノ酸療法に用いられる方法と全く同じであ
る。内服用錠剤、即ち糖衣錠、静脈（即ち、中枢静脈
の）内注射液の形で投与される。The therapeutic administration of these compounds is essentially the same as that used for any amino acid therapy. It is administered in the form of a tablet for internal use, that is, a sugar-coated tablet, an intravenous (that is, central vein) injection solution.
ヒドロキシプロリンの投与量範囲は、１日、0.01及至0.
1g/kgで、重い場合には、0.2g/kgまでとすることもあ
る。The dose range of hydroxyproline is 0.01 to 0 per day.
1g / kg, sometimes up to 0.2g / kg if heavy.
プロリン，バリン，アラニン，リジン，ヒドロキシリジ
ン，およびグリシンと併用されるヒドロキシプロリンに
関する含有量の範囲は、ヒドロキシプロリン0.006乃至
0.06g/kgに対し、ヒドロキシプロリン以外の前記各アミ
ノ酸を、0.003乃至0.03g/kgずつ含むような量である。The content range for hydroxyproline in combination with proline, valine, alanine, lysine, hydroxylysine, and glycine ranges from 0.006 to hydroxyproline.
The amount of each amino acid other than hydroxyproline is 0.003 to 0.03 g / kg, relative to 0.06 g / kg.
Claims (4)
有することを特徴とする、癌及び関連腫瘍を治療する薬
剤。1. A drug for treating cancer and related tumors, which comprises cis-4-hydroxy-L-proline.
01〜0.2g/kgで投与される、特許請求の範囲第１項に記
載の薬剤。2. A daily dose of cis-4-hydroxy-proline of 0.
The drug according to claim 1, which is administered at 01 to 0.2 g / kg.
リン、アラニン、リジン、ヒドロキシリジン及びグリシ
ンと組み合わせて含有することを特徴とする、癌及び関
連腫瘍を治療する薬剤。3. A drug for treating cancer and related tumors, which comprises cis-4-hydroxy-L-proline in combination with valine, alanine, lysine, hydroxylysine and glycine.
0.01〜0.2g/kgで投与される、特許請求の範囲第３項に
記載の薬剤。4. A daily dose of cis-4-hydroxy-proline.
The drug according to claim 3, which is administered at 0.01 to 0.2 g / kg.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US66820084A | 1984-11-05 | 1984-11-05 | |
| US72356585A | 1985-04-15 | 1985-04-15 | |
| US668200 | 1985-04-15 | ||
| US723565 | 2003-11-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61155324A JPS61155324A (en) | 1986-07-15 |
| JPH0723309B2 true JPH0723309B2 (en) | 1995-03-15 |
Family
ID=27099851
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24642585A Expired - Fee Related JPH0723309B2 (en) | 1984-11-05 | 1985-11-05 | Cancer treatment |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPH0723309B2 (en) |
| CA (1) | CA1281288C (en) |
| CH (1) | CH667591A5 (en) |
| DE (1) | DE3538619C2 (en) |
| GB (1) | GB2171302B (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1987004925A1 (en) * | 1986-02-18 | 1987-08-27 | Biota Scientific Management Pty. Ltd. | Stimulation of angiogenesis |
| DE3728852C2 (en) * | 1987-08-28 | 2003-06-18 | Wilhelm Hoerrmann | Medicines for tumor therapy |
| EP0307390A3 (en) * | 1987-09-04 | 1991-04-10 | Merckle Gmbh | Chemical compound consisting of cis-3-hydroxyproline for therapeutic treatment, and process for its preparation |
| US5827874A (en) * | 1995-05-05 | 1998-10-27 | Meyer; Hans | Methods of treating pain and inflammation with proline |
| WO1997033578A1 (en) * | 1996-03-11 | 1997-09-18 | Wilhelm Hoerrmann | Combination of cis-4-hydroxy-l-proline and n-methyl-cis-4-hydroxy-l-proline for use as a therapeutic agent, in particular in cancer treatment |
| CZ330498A3 (en) * | 1996-04-16 | 1999-07-14 | Chephasaar Chem.-Pharm. Fabrik Gmbh | Use of hydroxyproline derivatives |
| DE10359828A1 (en) * | 2003-12-12 | 2005-07-28 | Zoser B. Dr.Rer.Nat. Salama | CHP gemcitabine combination agents and their use as antitumor agents, in particular anti-metastatic agents |
| DE10359829A1 (en) * | 2003-12-12 | 2005-07-21 | Salama, Zoser B., Dr.Rer.Nat. | Use of CHP as inhibitor of glutathione-S-transferases and collagen IV |
| CA2548391A1 (en) * | 2003-12-18 | 2005-06-30 | Zoser B. Salama | Proline derivatives used as pharmaceutical active ingredients for the treatment of tumours |
| WO2005120495A1 (en) | 2004-06-14 | 2005-12-22 | Salama Zoser B | Anti-cancer composition comprising proline or its derivatives and an anti-tumour antibody |
| WO2007059047A2 (en) | 2005-11-11 | 2007-05-24 | Chandran V Ravi | Acetylated amino acids as anti-platelet agents, nutritional and vitamin supplements |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3932638A (en) * | 1967-09-14 | 1976-01-13 | Franco-Chimie S.A.R.L. | Compositions and methods for wound healing |
| FR7639M (en) * | 1967-09-14 | 1970-02-02 | ||
| GB1399887A (en) * | 1971-06-10 | 1975-07-02 | Prockop D J | Composition and methods for controlling collagen synthesis |
| FR2207702B1 (en) * | 1972-11-23 | 1975-11-28 | Rhone Poulenc Ind | |
| JPS59164718A (en) * | 1983-03-10 | 1984-09-17 | Advance Res & Dev Co Ltd | Preventive for cancer |
-
1985
- 1985-10-24 CA CA000493821A patent/CA1281288C/en not_active Expired - Lifetime
- 1985-10-29 CH CH4616/85A patent/CH667591A5/en not_active IP Right Cessation
- 1985-10-30 DE DE3538619A patent/DE3538619C2/en not_active Expired - Lifetime
- 1985-11-04 GB GB8527159A patent/GB2171302B/en not_active Expired
- 1985-11-05 JP JP24642585A patent/JPH0723309B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| GB2171302B (en) | 1989-08-23 |
| JPS61155324A (en) | 1986-07-15 |
| GB2171302A (en) | 1986-08-28 |
| DE3538619A1 (en) | 1986-05-07 |
| CH667591A5 (en) | 1988-10-31 |
| DE3538619C2 (en) | 1995-11-09 |
| CA1281288C (en) | 1991-03-12 |
| GB8527159D0 (en) | 1985-12-11 |
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| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |