JPS6348225A - Carcinostatic agent - Google Patents
Carcinostatic agentInfo
- Publication number
- JPS6348225A JPS6348225A JP61192169A JP19216986A JPS6348225A JP S6348225 A JPS6348225 A JP S6348225A JP 61192169 A JP61192169 A JP 61192169A JP 19216986 A JP19216986 A JP 19216986A JP S6348225 A JPS6348225 A JP S6348225A
- Authority
- JP
- Japan
- Prior art keywords
- bleomycin
- ifn
- alpha
- carcinostatic agent
- administered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000003327 cancerostatic effect Effects 0.000 title abstract 3
- 102000006992 Interferon-alpha Human genes 0.000 claims abstract description 19
- 108010047761 Interferon-alpha Proteins 0.000 claims abstract description 19
- 108010006654 Bleomycin Proteins 0.000 claims abstract description 15
- 229960001561 bleomycin Drugs 0.000 claims abstract description 15
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims abstract description 15
- 206010023825 Laryngeal cancer Diseases 0.000 claims description 11
- 206010023841 laryngeal neoplasm Diseases 0.000 claims description 11
- 239000002246 antineoplastic agent Substances 0.000 claims description 9
- 230000002708 enhancing effect Effects 0.000 claims description 2
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 6
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 abstract description 3
- 102000003886 Glycoproteins Human genes 0.000 abstract description 2
- 108090000288 Glycoproteins Proteins 0.000 abstract description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 abstract description 2
- 238000010353 genetic engineering Methods 0.000 abstract description 2
- 238000010255 intramuscular injection Methods 0.000 abstract description 2
- 239000007927 intramuscular injection Substances 0.000 abstract description 2
- 238000010253 intravenous injection Methods 0.000 abstract description 2
- 210000000265 leukocyte Anatomy 0.000 abstract description 2
- 201000005264 laryngeal carcinoma Diseases 0.000 abstract 2
- 241001147844 Streptomyces verticillus Species 0.000 abstract 1
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
- 230000003115 biocidal effect Effects 0.000 abstract 1
- 238000002347 injection Methods 0.000 abstract 1
- 239000007924 injection Substances 0.000 abstract 1
- 230000002476 tumorcidal effect Effects 0.000 abstract 1
- 241001446247 uncultured actinomycete Species 0.000 abstract 1
- 229940041181 antineoplastic drug Drugs 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 241000186361 Actinobacteria <class> Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000831652 Salinivibrio sharmensis Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（イ）産業上の利用分野
本発明は、喉頭癌治療においてブレオマイシンを用いる
際に、作用増強を目的として投与することを特徴とする
インターフェロン−α（以下、ＩＦＮ−αと省略）を主
成分とする制癌剤に関する。DETAILED DESCRIPTION OF THE INVENTION (a) Industrial application field The present invention provides interferon-α (hereinafter referred to as IFN-α), which is administered for the purpose of enhancing the action when bleomycin is used in the treatment of laryngeal cancer. It relates to an anticancer drug whose main ingredient is
（ロ）従来技術
ＩＦＮ−αのヒト由来癌細胞に対する増殖抑制活性は既
にインビトロのみでな≦ごヌードマウスを世いたインビ
ボにおいても検討され、Ｉ ＦＮ−αが癌細胞の増殖を
抑制することが明らかにされている〔インターフェロン
（Ｉｎｔｅｒｆｅｒｏｎ）、、 ２ ＋ 、１３−４
６（１９８０） ；ジャーナル・オブ・インターフェロ
ン・リサーチ（Ｊ、Ｉｎｔｅｒｆｅｒｏｎ Ｒｅｓ、）
＋ ２ （４１，４７９−４９１（１９８２） ）。(b) Conventional technology The growth-suppressing activity of IFN-α against human-derived cancer cells has already been investigated not only in vitro, but also in vivo in nude mice, and it has been demonstrated that IFN-α suppresses the growth of cancer cells. It has been revealed [Interferon, 2+, 13-4
6 (1980); Journal of Interferon Research (J, Interferon Res)
+2 (41, 479-491 (1982)).
このＩＦＮ−αは既存の制癌剤とは異なった作用機序を
有するものと考えられている〔基礎と臨床、 １９（，
１１）、 ３３９−３４６（１９８５） ）。This IFN-α is thought to have a different mechanism of action from existing anticancer drugs [Basic and Clinical Research, 19 (,
11), 339-346 (1985)).
一般に、制癌剤は副作用も顕著であり、そのために、体
薬期間を置いたり１．数種の制癌剤を少量ずつ併用する
措置などが取られている。In general, anticancer drugs have significant side effects, and for this reason, it is necessary to take a period of physical therapy or 1. Measures are being taken to combine small doses of several anticancer drugs.
（ハ）本発明が解決しようとする問題点そこで、既存の
制癌剤と作用機序の異なるＩＦＮ−αを併用することに
より、各々の薬剤を単独で投与する場合に比べて高い抗
腫瘍効果の得られやことが示唆されている。(c) Problems to be solved by the present invention Therefore, by combining existing anticancer drugs with IFN-α, which has a different mechanism of action, a higher antitumor effect can be obtained than when each drug is administered alone. It has been suggested that this is the case.
本発明者らは、このような示唆に基づき、ＩＦＮ−αと
既存の制癌剤であるブレオマイシンの併用による癌治療
効果について検討した。そして、喉頭癌について併用効
果があることを見出して、本発明を完成した。Based on this suggestion, the present inventors investigated the cancer therapeutic effect of the combination of IFN-α and bleomycin, an existing anticancer drug. Then, they discovered that the combination had an effect on laryngeal cancer, and completed the present invention.
従って、本発明の目的は、ブレオマイシンとＩＦＮ−α
を併用することにより、喉頭癌を治療する方法を提供す
ることにある。Therefore, the object of the present invention is to combine bleomycin and IFN-α
The object of the present invention is to provide a method for treating laryngeal cancer by using the above-mentioned methods in combination.
（ニ）問題点を解決するための手段
本発明のＩＦＮ−αは、分子量１５０００〜２４０００
、アミノ酸１６５あるいは１６６個の糖蛋白である。そ
して、その由来は、ヒト由来のものであれば、培養（白
血球、リンパ芽球など）、あるいは遺伝子工学の手法に
より製造されたものであってもよい。(d) Means for solving the problems The IFN-α of the present invention has a molecular weight of 15,000 to 24,000.
, a glycoprotein of 165 or 166 amino acids. As long as the origin is human, it may be cultured (leukocytes, lymphoblasts, etc.) or produced by genetic engineering techniques.
その結果としてはｌＸｌ０’〜１ ｘｌＯ” ＩＵ／■
程度であればよい。As a result, lXl0'~1 xlO'' IU/■
It is sufficient as long as it is of a certain extent.
ＩＦＮ−αの製法としては、アンチマイクロボアル・エ
ージェント・アンド・ケモセラピイ（Ａｎｔｉｍｉｃｒ
ｏｂｏａｌ＾ｇｅｎｔ ａｎｄ Ｃｈｅｍｏｔｈｅｒａ
ｐｙ ２０（１）＋５、１９８１）などに記載の方法が
挙げられる。The manufacturing method for IFN-α is antimicroboal agent and chemotherapy (Antimicr).
oboal＾gent and Chemothera
py 20(1)+5, 1981).
また、ブレオマイシンは、放線菌（ストレプトマイセス
・バルチシウスＢ ８０−７２株）の培養液力ら分離さ
れた抗腫瘍性抗生物質であり、臨床的には、塩酸塩、硫
酸塩などが用いられている。（通常の使用量は５〜３０
■／回程度である。）投与量としては、患者の年齢・病
態等に応じて、ＩＦＮ−αは１０４〜１０９ＩＩ／ｋｇ
／回、ブレオマイシンは０．０１〜５０■／ ｋｇ ／
同程度とすることが好ましい。Bleomycin is an antitumor antibiotic isolated from the culture solution of actinomycetes (Streptomyces balticius strain B 80-72), and its hydrochloride, sulfate, etc. are used clinically. There is. (Usually used amount is 5-30
■About 1/time. ) The dosage for IFN-α is 104 to 109 II/kg, depending on the patient's age and condition.
/time, bleomycin 0.01-50■/kg/
It is preferable that they be at the same level.
投与方法としては、各々の薬物の一回投与分を適当な溶
媒（生理食塩液、糖液など）１〜２０ｍ１程度に溶解し
た後、静注・皮下・筋注などで併用投与される。投与時
期は、同時でもよいが、適宜治療期間中においてずらし
て投与してもよい。As for the administration method, a single dose of each drug is dissolved in about 1 to 20 ml of an appropriate solvent (physiological saline, sugar solution, etc.), and then the drugs are administered together by intravenous, subcutaneous, or intramuscular injection. The administration timing may be simultaneous, or may be administered at appropriate times during the treatment period.
本発明で有効な対象癌としては、喉頭癌が挙げられる。Target cancers that are effective in the present invention include laryngeal cancer.
特に、ヒト喉頭癌細胞株ＨＥｐ −２（ＡＴＣＣ−ＣＬ
Ｌ２３）に由来する喉頭癌に対して極めて有効である。In particular, human laryngeal cancer cell line HEp-2 (ATCC-CL
It is extremely effective against laryngeal cancer derived from L23).
（ホ）本発明の効果
本発明によれば、ブレオマイシンとＩＦＮ−αを併用す
ることにより喉頭癌の治療に対して相乗効果を期待でき
る。(e) Effects of the present invention According to the present invention, a synergistic effect can be expected in the treatment of laryngeal cancer by using bleomycin and IFN-α together.
従って、従来の制癌剤ブレオマイシンの投与量を減らす
ことが可能となり、副作用の軽減を図ることもできる。Therefore, it is possible to reduce the dose of the conventional anticancer drug bleomycin, and it is also possible to reduce side effects.
（へ）実施例・実験例
本発明をさらに詳細に説明するために、実施例・実験例
を挙げるが、本発明はこれらによって限定されるもので
はない。(f) Examples and Experimental Examples In order to explain the present invention in more detail, Examples and Experimental Examples will be given, but the present invention is not limited by these.
実験例１
ヒトｖＩ＆頭癌）（ｕｐ−２を移植したヌードマウスを
用いて、ＩＦＮ−αとブレオマイシンの併用効果につい
て検討した。Experimental Example 1 The combined effect of IFN-α and bleomycin was investigated using nude mice transplanted with human vI & head cancer (up-2).
ヌードマウス（雄性、 Ｂａ１ｂ／ｃ系＋ ｎｕ／ｎｕ
＋ ５週令）の背部皮下にヒト喉頭癌由来ＨＥｐ−２株
（ＡＴＣＣ−ＣＬＬ２３） ５Ｘ１０６細胞数を移植
した。Nude mouse (male, Ba1b/c line + nu/nu
5×10 6 cells of human laryngeal cancer-derived HEp-2 strain (ATCC-CLL23) were subcutaneously transplanted into the back of a mouse (+5 weeks old).
癌細胞移植後、腫瘍径が５’ １０ｍｍ程度に増殖し
たマウスを一群４匹ずつに群分けした。After cancer cell transplantation, the mice whose tumors had grown to about 5' 10 mm in diameter were divided into groups of 4 mice per group.
投与スケジュールは、ＩＦＮ−αは、皮下へ週５回連続
投与で４週間、ブレオマイシンは腹腔内へ７目間隔で２
回投与とした（第１表）。The administration schedule was as follows: IFN-α was administered subcutaneously 5 times a week for 4 weeks, and bleomycin was administered intraperitoneally 2 times every 7 days.
It was administered twice (Table 1).
Claims (2)
、作用増強を目的として投与することを特徴とするイン
ターフェロン−αを主成分とする制癌剤。(1) An anticancer agent containing interferon-α as a main component, which is administered for the purpose of enhancing the action when bleomycin is used in the treatment of laryngeal cancer.
特許請求の範囲第（１）項記載の制癌剤。(2) The anticancer agent according to claim (1), wherein the laryngeal cancer is derived from the human laryngeal cancer cell line HEp-2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61192169A JPS6348225A (en) | 1986-08-19 | 1986-08-19 | Carcinostatic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61192169A JPS6348225A (en) | 1986-08-19 | 1986-08-19 | Carcinostatic agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6348225A true JPS6348225A (en) | 1988-02-29 |
Family
ID=16286831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61192169A Pending JPS6348225A (en) | 1986-08-19 | 1986-08-19 | Carcinostatic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6348225A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999027908A1 (en) * | 1997-12-04 | 1999-06-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Combined chemo-immunotherapy with liposomal drugs and cytokines |
-
1986
- 1986-08-19 JP JP61192169A patent/JPS6348225A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999027908A1 (en) * | 1997-12-04 | 1999-06-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Combined chemo-immunotherapy with liposomal drugs and cytokines |
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