JPH04149133A - Cell differentiation inducing agent - Google Patents
Cell differentiation inducing agentInfo
- Publication number
- JPH04149133A JPH04149133A JP2273031A JP27303190A JPH04149133A JP H04149133 A JPH04149133 A JP H04149133A JP 2273031 A JP2273031 A JP 2273031A JP 27303190 A JP27303190 A JP 27303190A JP H04149133 A JPH04149133 A JP H04149133A
- Authority
- JP
- Japan
- Prior art keywords
- cell differentiation
- agent
- inducing agent
- cotylenin
- differentiation inducing
- 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
- 230000024245 cell differentiation Effects 0.000 title claims abstract description 25
- 230000001939 inductive effect Effects 0.000 title abstract description 12
- 239000000411 inducer Substances 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 239000002246 antineoplastic agent Substances 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 abstract description 12
- 206010028980 Neoplasm Diseases 0.000 abstract description 11
- 201000011510 cancer Diseases 0.000 abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 8
- 229930191230 Cotylenin Natural products 0.000 abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 6
- 230000004069 differentiation Effects 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 2
- 241000222290 Cladosporium Species 0.000 abstract description 2
- 239000001888 Peptone Substances 0.000 abstract description 2
- 108010080698 Peptones Proteins 0.000 abstract description 2
- 229930006000 Sucrose Natural products 0.000 abstract description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 abstract description 2
- 240000008042 Zea mays Species 0.000 abstract description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 abstract description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 abstract description 2
- 230000001580 bacterial effect Effects 0.000 abstract description 2
- 229960001701 chloroform Drugs 0.000 abstract description 2
- 235000005822 corn Nutrition 0.000 abstract description 2
- 239000000706 filtrate Substances 0.000 abstract description 2
- 238000001990 intravenous administration Methods 0.000 abstract description 2
- 235000019319 peptone Nutrition 0.000 abstract description 2
- 238000010898 silica gel chromatography Methods 0.000 abstract description 2
- 241000894007 species Species 0.000 abstract description 2
- 239000005720 sucrose Substances 0.000 abstract description 2
- 230000003327 cancerostatic effect Effects 0.000 abstract 2
- 230000006698 induction Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 11
- 238000009472 formulation Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 238000012258 culturing Methods 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- NNJPGOLRFBJNIW-HNNXBMFYSA-N (-)-demecolcine Chemical compound C1=C(OC)C(=O)C=C2[C@@H](NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-HNNXBMFYSA-N 0.000 description 1
- ILFPCMXTASDZKM-YFKPBYRVSA-N (1s)-2-methylidene-3-oxocyclopentane-1-carboxylic acid Chemical compound OC(=O)[C@H]1CCC(=O)C1=C ILFPCMXTASDZKM-YFKPBYRVSA-N 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 241000219193 Brassicaceae Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- NNJPGOLRFBJNIW-UHFFFAOYSA-N Demecolcine Natural products C1=C(OC)C(=O)C=C2C(NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-UHFFFAOYSA-N 0.000 description 1
- 229940123414 Folate antagonist Drugs 0.000 description 1
- 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045713 antineoplastic alkylating drug ethylene imines Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- -1 carcinophilin Chemical compound 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 239000007931 coated granule Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 229940125697 hormonal agent Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000003790 pyrimidine antagonist Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- ILFPCMXTASDZKM-UHFFFAOYSA-N sarkomycin Natural products OC(=O)C1CCC(=O)C1=C ILFPCMXTASDZKM-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発肋は細胞分化誘導剤に関し、さらに詳しくは制癌剤
等として臨床上有用な細胞分化誘導剤、及び該細胞分化
誘導剤を有効成分として含有する細胞分化誘導剤組成物
に関する。Detailed Description of the Invention (Industrial Field of Application) The present invention relates to a cell differentiation inducer, more specifically a cell differentiation inducer clinically useful as an anticancer agent, and a cell differentiation inducer containing the cell differentiation inducer as an active ingredient. The present invention relates to a cell differentiation inducer composition.
（従来の技術）
従来、癌化学療法剤としては、アルキル化剤くニトロジ
エンマスタード類、エチレンイミン類、スルホン酸エス
テル類等）、代謝拮抗物質（葉酸拮抗剤、ピリミジン拮
抗剤等）、植物性核分裂前（コルセミド、ビンブラスチ
ン等）、抗生物質（ザルコマイシン、カルチノフィリン
、マイトマイシン等）、ホルモン剤く副腎皮質ステロイ
ド、男性ホルモン、女性ホルモン等）、及びポルフィリ
ン錯塩（モーフィリン、ｃ ｏ ｐ ｐ）等が臨床上使
用されている。しかし、これらの癌化学療法剤の大部分
は細胞毒型の物質であり投与量や投与方法によっては重
大な副作用を呈するという問題があった。従って、低毒
１生で、かつ優れた制癌活性を有する制癌剤の開発が望
まれていた。(Prior art) Conventionally, cancer chemotherapy agents include alkylating agents (nitrogien mustards, ethyleneimines, sulfonic acid esters, etc.), antimetabolites (folate antagonists, pyrimidine antagonists, etc.), and plant-based Before nuclear fission (colcemid, vinblastine, etc.), antibiotics (sarcomycin, carcinophilin, mitomycin, etc.), hormonal agents (corticosteroids, male hormones, female hormones, etc.), and porphyrin complex salts (morphilin, copp), etc. Used clinically. However, most of these cancer chemotherapeutic agents are cytotoxic substances and have the problem of exhibiting serious side effects depending on the dosage and administration method. Therefore, it has been desired to develop an anticancer agent that is low in toxicity and has excellent anticancer activity.
一方、癌細胞は正常細胞が分化の途中で未分化のまま増
殖を繰り返すものであるという認識から、これら未分化
癌細胞を何らかの刺激によって分化させることができれ
ば癌治療に応用できるものと期待される。On the other hand, based on the recognition that cancer cells are normal cells that repeatedly proliferate while remaining undifferentiated during the differentiation process, it is expected that if these undifferentiated cancer cells can be differentiated by some kind of stimulation, it will be possible to apply them to cancer treatment. .
（発明が解決しようとする課題）
従って、本発明は細胞分化誘導活性に優れ、癌細胞を正
常成熟細胞へ分化させることにより臨床において制癌剤
等として有用な細胞分化誘導剤を提供することを目的と
する。(Problems to be Solved by the Invention) Therefore, an object of the present invention is to provide a cell differentiation-inducing agent that has excellent cell differentiation-inducing activity and is useful as an anticancer agent in the clinic by differentiating cancer cells into normal mature cells. do.
また、本発明は該細胞分化誘導剤を有効成分として含有
する細胞分化誘導剤組成物を提供することを目的とする
。Another object of the present invention is to provide a cell differentiation inducer composition containing the cell differentiation inducer as an active ingredient.
く課題を解決するための手段）
本発明者は、上記の課題を解決すべく細胞分化誘導活性
の優れた化合物を鋭意探索した結果、下記の構造を有す
るコチレニンＣが極めて優れた細胞分化誘導活性を有し
、かつコチレニンＣが癌細胞を正常分化させることにに
より制癌剤として有用であることを見出し、本発明を完
成するに至った。Means for Solving the Problems) In order to solve the above problems, the present inventors have diligently searched for compounds with excellent cell differentiation-inducing activity, and have discovered that cotyrenin C, which has the following structure, has extremely excellent cell differentiation-inducing activity. The present inventors have discovered that cotylenin C is useful as an anticancer agent by causing normal differentiation of cancer cells, and has completed the present invention.
コチレニンＣは下記の構造を有する植物活性配糖体であ
り、植物成長促進活性を有することが知られている（Ｔ
、 ５ａｓｓａ ｅｔ ａｌ、 Ａｇｒ、 Ｂｉｏｌ、
Ｃｈｅｍ。Cotyrenin C is a plant active glycoside having the following structure, and is known to have plant growth promoting activity (T
, 5assa et al., Agr., Biol.
Chem.
３９（１１） ２２１３〜２２１５．１９７５）。39(11) 2213-2215.1975).
コチレニンＣは、クラドスポリウム
（［：］ａｄｏｓｐｏｒｉｕｍ）属の新種と思われる１
菌種（ストレイン５０１−７Ｗ＞を、蔗糖３％、ペプト
ン０．５％、コーンステイープ０．５％を含む培地で６
日間、２８℃で振盪培養した後に、得られた培養濾液を
酢酸エチルで抽圧し、該抽出液を減圧濃縮してシリカゲ
ルカラムクロマトグラフィー（トリクロロメタン：エタ
ノール＝１００：４）に付すことにより得ることができ
る。通常、培養液５βから２５ｍｇのコチレニンＣｉｆ
ｉｇられる。Cotylenin C is thought to be a new species of the genus Cladosporium ([:]adosporium).
strain 501-7W> in a medium containing 3% sucrose, 0.5% peptone, and 0.5% corn staple.
After culturing with shaking at 28°C for 1 day, the resulting culture filtrate is extracted with ethyl acetate, the extract is concentrated under reduced pressure and subjected to silica gel column chromatography (trichloromethane:ethanol = 100:4). I can do it. Usually, 25 mg of cotyrenine Cif from culture solution 5β
I'll be igted.
本発明はコチレニンＣの細胞分化誘導剤としての新規用
途を提供するものである。The present invention provides a new use of cotyrenin C as a cell differentiation inducer.
以下に実施例によりコチレニンＣの細胞分化誘導活性を
説明する。The cell differentiation-inducing activity of cotylenin C will be explained below using Examples.
（実施例）
ＧＩＢＣＯ製イーグルＭＥＭ培地に１０％の馬血清及び
６０ｍｇ／Ａのカナマイシンを加えたものに、５． Ｏ
Ｘ １０ ’ ｃｅｌｌ／ｍｆとなるようにＭ１細胞を
接種し、これに所定量の被験化合物を加えた（最終容量
５ｍｆ）。(Example) To GIBCO's Eagle MEM medium to which 10% horse serum and 60 mg/A kanamycin were added, 5. O
M1 cells were inoculated at a density of X 10' cells/mf, and a predetermined amount of the test compound was added thereto (final volume: 5 mf).
７．５％［０゜中、３７℃７日間培養した後、貧食細胞
あるいは顆粒球への分化により誘導されたりゾチーム活
性を調べた。After culturing at 7.5% [0° and 37°C for 7 days, zozyme activity induced by differentiation into phagocytic cells or granulocytes was examined.
なお、リゾチーム活性の１単位（ｕｎｉｔ；［１）とは
、ミクロコツカス・リソ′デイクテイカス（Ｍｉｃｒｏ
ｃｏｃｃｕｓｌｙｓｏｃｌｅｉｋｔｉｃｕｓ）菌体の懸
濁液を基質として、リゾチームを作用させ、ｐＨ６，２
４、温度２５℃で測定し、４５０ｍμの波長の吸光度を
毎分０．００１減少させるようｔ ’Ｊゾチームの量を
いう。活性試験の結果を第１表に示す。In addition, one unit (unit; [1) of lysozyme activity is Micrococticus lyso'deicteichus (Micrococticus).
lysozyme was applied using a suspension of bacterial cells (Coccus lysocleikticus) as a substrate, and the pH was adjusted to 6.2.
4. It is measured at a temperature of 25°C and refers to the amount of t'J zozyme that reduces the absorbance at a wavelength of 450 mμ by 0.001 per minute. The results of the activity test are shown in Table 1.
第１表
＊
エタノール
濃度
１．０％
本発明の細胞分化誘導剤は、例えば制癌剤、技部ジスト
ロフィー剤等として有用である。癌患者に制癌剤として
投与する場合には、経口投与、直腸内投与、静脈内若し
くは筋肉内投与等の全身投与の他、癌組織に対しての局
所投与や経皮的投与等の種々の投与経路により患者にす
ればよい。投与量は静脈内投与による場合には通常成人
１日あたり１〜１００ ｍｇ／ｋｇ程度、経口投与によ
る場合には通常成人１日あたり５〜５００ｍｇ程度を１
日あたり１〜３回、若しくは２〜５日おきに投与すれば
よいが、癌の種類や進行程度、患者の年齢、症状、治療
目的、投与経路等により適宜増減させるべきである。尚
、本発明の細胞分化誘導剤の急性毒性はマウスに腹腔内
投与した場合に、Ｌ Ｄ ｓｏ ＞ １００ ｍｇ／
ｋｇである。Table 1 *Ethanol concentration 1.0% The cell differentiation inducer of the present invention is useful as, for example, an anticancer agent, an agent for dystrophy, and the like. When administered as an anticancer drug to cancer patients, various routes of administration are available, including systemic administration such as oral administration, intrarectal administration, intravenous or intramuscular administration, as well as local administration to cancer tissues and transdermal administration. Depending on the patient. The dosage is usually about 1 to 100 mg/kg per day for adults when administered intravenously, and about 5 to 500 mg per day for adults when administered orally.
The dose may be administered 1 to 3 times per day or every 2 to 5 days, but the dose should be increased or decreased as appropriate depending on the type and degree of progression of the cancer, patient age, symptoms, therapeutic purpose, administration route, etc. In addition, the acute toxicity of the cell differentiation inducing agent of the present invention when administered intraperitoneally to mice is L D so > 100 mg/
kg.
本発明の細胞分化誘導剤は製剤挙上一般的に使用される
他の製剤成分とともに細胞分化誘導剤組成物とすること
が好ましい。該組成物としては、例えば注射剤、点滴剤
、カプセル剤、錠剤、顆粒剤、細粒剤、シロップ剤、点
眼剤、点耳剤、経皮吸収剤、腸溶性カプセル剤、廃剤等
を例示することができる。製剤成分としては、乳糖、結
晶セルロース等の賦形剤、カルボキシメチルセルロース
等の崩壊剤、ヒドロキシプロピルセルロース等の結合剤
、ステアリン酸マグネシウム等の滑沢剤、ヒドロキシプ
ロピルメチルセルロース等のコーティング剤、ポリエチ
レングリコール等の基剤、生理食塩水等の溶解補助剤、
無機酸等のｐＨ調節剤、塩化ナトリウム等の等張化剤若
しくは安定化剤を挙げることができる。The cell differentiation-inducing agent of the present invention is preferably formulated into a cell differentiation-inducing agent composition together with other commonly used formulation components. Examples of the composition include injections, drops, capsules, tablets, granules, fine granules, syrups, eye drops, ear drops, transdermal absorption agents, enteric-coated capsules, and waste preparations. can do. Formulation components include excipients such as lactose and crystalline cellulose, disintegrants such as carboxymethylcellulose, binders such as hydroxypropylcellulose, lubricants such as magnesium stearate, coating agents such as hydroxypropylmethylcellulose, polyethylene glycol, etc. base, solubilizing agent such as physiological saline,
Mention may be made of pH regulators such as inorganic acids, tonicity agents or stabilizers such as sodium chloride.
以下に製剤例を具体的に示す。Specific formulation examples are shown below.
製剤例１ く注射・点滴剤）
コチレニンＣｌ０ｍｇを含有するように粉末ぶどうＰ５
ｇを加えてバイアルに無菌的に分配し、密封した上、窒
素、ヘリウム等の不活性ガスを封入して冷暗所に保存す
る。使用前に含水エタノールに溶解し、０．８５％生理
的食塩水１．００−を添加して静脈内注射液とし、１日
、１０〜１００−を症状に応じて静脈内注射又は点滴で
投与する。Formulation Example 1 Injection/Drip) Powdered grape P5 containing 0 mg of cotylenin Cl.
g and aseptically dispensed into vials, sealed, sealed with an inert gas such as nitrogen or helium, and stored in a cool, dark place. Before use, dissolve in aqueous ethanol and add 0.85% physiological saline to make an intravenous injection, and administer 10 to 100 by intravenous injection or drip depending on symptoms per day. do.
製剤例２（注射・点滴剤）
コチレニンＣ２ｍｇを用いて、製剤例１と同様の方法に
より軽症用静脈内注射剤とし、１巳、１０〜１．００−
を症状に応じて静脈内注射又は点滴で投与する。Formulation Example 2 (Injection/Drop) Using 2 mg of cotyrenine C, an intravenous injection for mild symptoms was prepared in the same manner as in Formulation Example 1, and 1 min., 10 to 1.00 -
Administer by intravenous injection or drip depending on the symptoms.
製剤例３ （腸溶性カプセル剤）
コチレニンＣ５ｇ、乳糖２．４６ ｇ及びヒドロキシプ
ロピルセルロース０．０４ｇを各々とり、ヨく混合した
後、常法に従って粒状に成形し、これをよく乾燥して篩
別してビン、ヒートシール包装などに適した顆粒剤を製
造する。次に、酢酸フタル酸セルロース０，５ｇ及びヒ
ドロキシプロピルメチルセルロースフタレート０．５
ｇを溶解して被覆基材となし、前記顆粒を浮遊流動させ
つ＼この基材を被覆して腸溶性の顆粒剤とする。この組
成物をカプセルに充填して腸溶性カプセル製剤１００個
を製造する。Formulation Example 3 (Enteric-coated capsules) 5 g of cotylenin C, 2.46 g of lactose, and 0.04 g of hydroxypropyl cellulose were each mixed thoroughly and formed into granules according to a conventional method, which was thoroughly dried and sieved. We manufacture granules suitable for bottles, heat seal packaging, etc. Next, 0.5 g of cellulose acetate phthalate and 0.5 g of hydroxypropyl methylcellulose phthalate
g is dissolved to form a coated base material, the granules are suspended and flowed, and this base material is coated to form enteric-coated granules. This composition is filled into capsules to produce 100 enteric-coated capsule preparations.
（発明の効果）
本発明により提供された細胞分化誘導剤は、例えば制癌
剤として使用した場合に癌細胞を殺すのではなく、
正常細胞へ分化誘導することにより制
癌効果を発揮するので副作用も少なく治療に有用である
。(Effects of the Invention) When the cell differentiation inducer provided by the present invention is used, for example, as an anticancer agent, it exhibits an anticancer effect by inducing differentiation into normal cells rather than killing cancer cells, and thus has few side effects. Useful for treatment.
平成
年
月
日
３、補正をする者
事件との関係
出
願
人
名
称
理
化
学
研
究
所
４、代
理
人
５、補正命令の日付
自
発
６、補正の対象
明細書の発明の詳細な説明の欄
（１） 明細書５頁２〜３行目の“６日間”を−４日
間 に訂正する。Date of Heisei 3, Person making the amendment Name of applicant related to the case: RIKEN 4, Agent 5, Date of amendment order Voluntary 6, Column for detailed explanation of the invention in the specification to be amended (1) Details Correct "6 days" in lines 2 and 3 on page 5 of the book to -4 days.
（２）同書同頁３行目の“培養した後に、得られた”を
−培養した後に、０５％炭酸カルシウムを加え、さろに
２日間、２８℃で振盪培養し、得られたヨ・に訂正する
。(2) "Obtained after culturing" in the third line of the same page of the same book - After culturing, 0.5% calcium carbonate was added and cultured with shaking at 28°C for 2 days. correct.
（３）同書９頁７行目の“コチレニンＣ５ｇ”をコチレ
ニンＣ５ｍｇ−に訂正する。(3) "Cotyrenine C5g" on page 9, line 7 of the same book is corrected to cotyrenine C5mg-.
Claims (2)
含有する細胞分化誘導剤組成物。（３）制癌剤として使
用することを特徴とする請求項１記載の細胞分化誘導剤
。(2) A cell differentiation inducer composition containing the cell differentiation inducer according to claim 1 as an active ingredient. (3) The cell differentiation inducer according to claim 1, which is used as an anticancer agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2273031A JPH07100659B2 (en) | 1990-10-11 | 1990-10-11 | Cell differentiation inducer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2273031A JPH07100659B2 (en) | 1990-10-11 | 1990-10-11 | Cell differentiation inducer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04149133A true JPH04149133A (en) | 1992-05-22 |
| JPH07100659B2 JPH07100659B2 (en) | 1995-11-01 |
Family
ID=17522208
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2273031A Expired - Lifetime JPH07100659B2 (en) | 1990-10-11 | 1990-10-11 | Cell differentiation inducer |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07100659B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117362366A (en) * | 2023-12-07 | 2024-01-09 | 云南大学 | Clostridin diterpenoid compound and preparation method and application thereof |
-
1990
- 1990-10-11 JP JP2273031A patent/JPH07100659B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117362366A (en) * | 2023-12-07 | 2024-01-09 | 云南大学 | Clostridin diterpenoid compound and preparation method and application thereof |
| CN117362366B (en) * | 2023-12-07 | 2024-02-06 | 云南大学 | Clostridin diterpenoid compound and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07100659B2 (en) | 1995-11-01 |
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