JPH0363533B2 - - Google Patents
Info
- Publication number
- JPH0363533B2 JPH0363533B2 JP58023867A JP2386783A JPH0363533B2 JP H0363533 B2 JPH0363533 B2 JP H0363533B2 JP 58023867 A JP58023867 A JP 58023867A JP 2386783 A JP2386783 A JP 2386783A JP H0363533 B2 JPH0363533 B2 JP H0363533B2
- Authority
- JP
- Japan
- Prior art keywords
- leukocidin
- cells
- myeloid leukemia
- administered
- staphylococcal
- 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.)
- Expired - Lifetime
Links
- 108010014603 Leukocidins Proteins 0.000 claims description 41
- 208000025113 myeloid leukemia Diseases 0.000 claims description 13
- 208000032839 leukemia Diseases 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 206010024305 Leukaemia monocytic Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 201000006894 monocytic leukemia Diseases 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 description 17
- 210000000265 leukocyte Anatomy 0.000 description 13
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 241000191940 Staphylococcus Species 0.000 description 5
- 241000191967 Staphylococcus aureus Species 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 230000002101 lytic effect Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 241000295644 Staphylococcaceae Species 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 210000004731 jugular vein Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 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
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000013587 production medium Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 238000007693 zone electrophoresis Methods 0.000 description 1
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
【発明の詳細な説明】
本発明はブドウ球菌ロイコシジンを用いた抗腫
瘍剤に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an antitumor agent using staphylococcal leukocidin.
ブドウ球菌、殊に病原性のブドウ球菌は菌体外
に多くの酵素や毒素を産生する。ロイコシジン
（leukocidin）はブドウ球菌菌体外毒素の１つで、
Van der Velde〔Cellule，10，401（1894）〕はヒ
ト化膿炎症巣から分離した黄色ブドウ球菌の培養
液のなかに溶血毒素とは別個に白血球を好んで
損傷する毒性物質を発見した。その後、Panton
等〔Lancet，１，506（1932）〕は溶血活性をもた
ずヒトとウサギの多核白血球を特異的に溶解する
毒素という意味でこの毒素をロイコシジンと名づ
けた。 Staphylococci, especially pathogenic staphylococci, produce many enzymes and toxins outside the bacterial body. Leukocidin is one of the staphylococcal exotoxins.
Van der Velde [Cellule, 10 , 401 (1894)] discovered a toxic substance in the culture of Staphylococcus aureus isolated from human pyogenic foci that, apart from hemolytic toxins, preferentially damages white blood cells. Then Panton
[Lancet, 1 , 506 (1932)] named this toxin leukocidin, meaning that it has no hemolytic activity and specifically lyses human and rabbit polynucleated leukocytes.
Woodin〔Biochem.J.，75，158（1960）〕はヒト
病巣から分離した黄色ブドウ球菌V8株を培養後、
ロイコシジンの精製は、その液をカルボキシメ
チルセルロース・カラムクロマトグラフーで塩濃
度によつて溶出される２成分をＦ成分とＳ成分と
名づけ、両成分の併用によつてはじめてロイコシ
ジンの白血球溶解活性が現われることを明らかに
した。また近年、加藤等〔Biochimica et
Biophysica Acta.633，33（1980），Infection
andImmunity，34(2)，362（1981），Infection
andImmunity，35(1)，38（1982）〕は黄色ブドウ
球菌V8株より得られたロイコシジンをカルボキ
シメチル−SephadexC−50。カラムクロマトグ
ラフイー，ゾーン電気泳動法を用いて精製し、前
述の２成分、ＦとＳの結晶化を行いその物理化学
的性質および白血球溶解作用の解明を行つてい
る。しかしながら、現在までこのロイコシジンを
医薬、例えば白血病等の疾患の治療薬として用い
た例はない。これはロイコシジンの白血球溶解作
用が正常多核白血球と白血病細胞との間に差がな
く、例えば全血液中の白血病細胞を全て溶解させ
ようとした場合、同時に全ての正常多核白血球も
溶解するという好ましくない結果が考えられたた
めである。このことは加藤等によつてなされれた
実験〔Infection and Immunity，34(2)，362
（1981）〕からも予測し得る。つまり、加藤等は、
125Iで標識したロイコシジンを用い、ヒト正常白
血球とヒト骨髄性白血病細胞に対する結合率を調
べ、両者の間には殆ど差がないという実験結果を
得ている。 Woodin [Biochem.J., 75 , 158 (1960)] cultivated Staphylococcus aureus V8 strain isolated from human lesions.
Leukocidin is purified by using carboxymethyl cellulose column chromatography, naming the two components F component and S component, which are eluted depending on the salt concentration, and the leukocidin's leukocyte lytic activity appears only when these two components are used together. revealed. In addition, in recent years, Kato et al.
Biophysica Acta. 633 , 33 (1980), Infection
andImmunity, 34(2) , 362 (1981), Infection
andImmunity, 35(1) , 38 (1982)] used carboxymethyl-SephadexC-50 to leukocidin obtained from Staphylococcus aureus V8 strain. We are purifying it using column chromatography and zone electrophoresis, crystallizing the two components mentioned above, F and S, and elucidating their physicochemical properties and leukocyte lytic action. However, to date, there has been no example of using this leukocidin as a medicine, for example, as a therapeutic agent for diseases such as leukemia. This is because there is no difference in the leukocyte lytic effect of leukocidin between normal polynucleated leukocytes and leukemia cells, and for example, if you try to lyse all leukemia cells in whole blood, all normal polynucleated leukocytes will be lysed at the same time, which is undesirable. This is because the results were considered. This was confirmed in an experiment conducted by Kato et al. [Infection and Immunity, 34(2) , 362]
(1981)]. In other words, Kato et al.
Using 125 I-labeled leukocidin, we investigated the binding rate to human normal leukocytes and human myeloid leukemia cells, and obtained experimental results that showed almost no difference between the two.
本発明者等はブドウ球菌ロイコシジン薬理作
用、殊にその抗腫瘍作用につき別途研究した結
果、種々の細胞のブドウ球菌ロイコシジンに対す
る感受性の差は細胞膜上のレセプター数に依存す
るのではなく、ロイコシジンＳがそのセレプター
であるガングリオシド（ganglioside）GM1に結合
することによつておこる白血球膜内のホスホリパ
ーゼA2の活性化の度合に依存していることが解
り、しかもブドウ球菌ロイコシジンが白血病中で
もヒトの骨髄性白血病細胞に対して極めて高い感
受性（細胞溶解作用）を示すという意外な事実を
見い出した。 As a result of separate research into the pharmacological effects of Staphylococcal leukocidin, particularly its antitumor effects, the present inventors found that the difference in sensitivity of various cells to Staphylococcus leukocidin does not depend on the number of receptors on the cell membrane, but rather on the leukocidin S It was found that staphylococcal leukocidin is dependent on the degree of activation of phospholipase A2 in the leukocyte membrane, which occurs by binding to its receptor ganglioside G M1 . We have discovered the surprising fact that it exhibits extremely high sensitivity (cytolytic action) to leukemia cells.
ブドウ球菌ロイコシジンの骨髄性白血病に対す
る感受性はヒトにおいて特に高く、例えばマウス
骨髄性白血病細胞C1498とヒト骨髄性白血病細胞
HL−60を用い、１×106個の白血球を溶解するブ
ドウ球菌ロイコシジンの最少量はC1498で250ng、
HL−60で5pgであり、５万倍感受性が違う。一
方ヒトの正常多核白血球１×106個を溶解させる
ブドウ球菌ロイコシジンの最少量は50pgであり、
骨髄性白血病細胞に対する感受性の1/10であり、
正常多核白血球に大きな影響を与えることなく骨
髄性白血病細胞を溶解させることが可能である。 The susceptibility of Staphylococcal leukocidin to myeloid leukemia is particularly high in humans, such as mouse myeloid leukemia cell C1498 and human myeloid leukemia cell.
Using HL-60, the minimum amount of staphylococcal leukocidin to lyse 1 x 10 6 leukocytes is 250 ng of C1498;
It is 5pg in HL-60, which is 50,000 times more sensitive. On the other hand, the minimum amount of staphylococcal leukocidin that can lyse 1 x 10 6 normal polynuclear leukocytes in humans is 50 pg.
1/10 of the sensitivity to myeloid leukemia cells,
It is possible to lyse myeloid leukemia cells without significantly affecting normal polynuclear leukocytes.
これらの事実は、従来公知の文献に何ら記載も
なく、また予測もし得ない新知見である。本発明
はこれらの新知見に基づき更に検討を加えて完成
したものである。すなわち本発明はブドウ球菌ロ
イコシジンを有効成分として含有する抗腫瘍剤に
関する。本発明が適用できる腫瘍としては、例え
ば骨髄性白血病、単球性白血病等の白血病であ
り、中でもヒトの骨髄性白血病に対し特に有効で
ある。 These facts have not been described in any conventionally known literature, and are new findings that could not have been predicted. The present invention was completed after further studies based on these new findings. That is, the present invention relates to an antitumor agent containing Staphylococcus leukocidin as an active ingredient. Tumors to which the present invention can be applied include, for example, leukemias such as myeloid leukemia and monocytic leukemia, among which it is particularly effective against human myeloid leukemia.
本発明でブドウ球菌ロイコシジンとは、ブドウ
球菌、殊に病原性のブドウ球菌から得られる白血
球溶解作用を有する毒素であり、具体的には黄色
ブドウ球菌V8株から加藤等の方法〔Biochimica
et Biophysica Acta，633，33，（1980）〕によつ
て得られる蛋白で分子量約31000のロイコシジン
Ｓと分子量約32000のロイコシジンＦの混合物で
ある。 In the present invention, staphylococcal leukocidin is a toxin with leukocyte lytic activity obtained from Staphylococcus, especially pathogenic Staphylococcus, and specifically, Staphylococcus leukocidin is obtained from Staphylococcus aureus V8 strain by the method of Kato et al.
et Biophysica Acta, 633 , 33, (1980)] and is a mixture of leukocidin S with a molecular weight of about 31,000 and leukocidin F with a molecular weight of about 32,000.
本発明の抗腫瘍効果はロイコシジンＳとロイコ
シジンＦの共同作用によるもので、最も好ましい
混合比は１：１であるが、その他の混合比で用い
ることも可能である。また最初ロイコシジンＳを
投与した後適当な期間を置いてロイコシジンＦを
投与しても本発明の抗腫瘍効果は得られ、このよ
うな態様も本発明に含まれる。 The antitumor effect of the present invention is due to the synergistic action of leukocidin S and leukocidin F, and the most preferred mixing ratio is 1:1, but other mixing ratios are also possible. Furthermore, the antitumor effect of the present invention can be obtained even if leukocidin F is administered after an appropriate period of time after the initial administration of leukocidin S, and such embodiments are also included in the present invention.
本発明のブドウ球菌ロイコシジンは常法に従い
所望の形態例えば注射剤、錠剤等に製剤化され投
与されるが、注射剤の形で投与するのが最も好ま
しい。１回の投与量は腫瘍の種類、製剤の形態に
よつて異なり、例えばヒトの成人に対しては1ng
〜10μgの間で適宜選択されるが、注射剤として
投与する場合は10ng〜100ngの範囲が好ましく、
錠剤として投与する場合は0.1μg〜2μgの範囲が好
ましい。 The staphylococcal leukocidin of the present invention is formulated and administered in a desired form, such as an injection or a tablet, according to a conventional method, but it is most preferably administered in the form of an injection. The dose per dose varies depending on the type of tumor and the form of the preparation, for example, 1 ng for adult humans.
It is appropriately selected between ~10 μg, but when administered as an injection, the range is preferably 10 ng to 100 ng.
When administered as a tablet, the dose is preferably in the range of 0.1 μg to 2 μg.
また、本発明のブドウ球菌ロイコシジンは、非
常に低毒性であり、医薬品として上記用量を用い
る場合、全く問題がない。 Furthermore, the staphylococcal leukocidin of the present invention has very low toxicity, and there is no problem at all when using it as a pharmaceutical at the above dosage.
参考例
黄色ブドウ球菌（Staphylococcus aureus）の
V8株（ATCCNo.27733）を毒素産生培地（yeast
−extract培地）で22時間、37℃振盪培養した後、
遠心によつて透明な上清を得た。これを出発材料
とし、まず塩化亜鉛の添加によつて濃縮し、リン
酸塩で脱イオン後0.2M食塩を含む0.05M酢酸緩
衝液（PH5.2）で平衡化したカルボキシメチル−
Sephadex Ｃ−50に吸着させ食塩濃度0.2〜1.2M
の直線的濃度勾配法によるカラムクロマトグラフ
イーを行つた。塩濃度0.45MでロイコシジンＦが
溶出し、塩濃度0.9MでロイコシジンＳが溶出し
た。このロイコシジンＦとＳの１：１（蛋白重量
当り）の混合物を食塩水に溶解し以下の実験に用
いた。Reference example: Staphylococcus aureus
V8 strain (ATCC No. 27733) was transferred to toxin production medium (yeast
-extract medium) for 22 hours at 37°C with shaking,
A clear supernatant was obtained by centrifugation. Using this as a starting material, carboxymethyl-
Adsorbed on Sephadex C-50 and salt concentration 0.2-1.2M
Column chromatography using the linear concentration gradient method was performed. Leukocidin F was eluted at a salt concentration of 0.45M, and leukocidin S was eluted at a salt concentration of 0.9M. This 1:1 (per protein weight) mixture of leukocidin F and S was dissolved in saline and used in the following experiment.
実施例 マウス骨髄性白血病治療効果
C57BL／６マウス（雌，５〜６週令）にマウ
ス骨髄性白血病C1498細胞（５×104個／マウス）
を頚静脈から注射し２週間以内に死亡する系を作
る。C1498細胞を移植後24時間目からマウス１匹
当り食塩水に溶解した参考例で得たブドウ球菌ロ
イコシジン（ロイコシジンＦとＳの１：１の混合
物）5.0μgを頚静脈から投与した。その際のマウ
スの延命率を図面に示す。図面中↓はロイコシジ
ンの１回の投与（5.0μg）を示し、数回投与する
場合は全て１日おきに行つた。なお実験は１群10
匹のマウスを用いた。対照群(A)はC1498細胞を移
植した後、食塩水だけを同様に投与したものであ
る。図面から明らかなように対照群はC1498細胞
を移植後全例が13日以内に死亡したのに対し、
C1498細胞を移植後ロイコシジン（5.0μg）を24
時間目から１日おきに４回投与した群(B)では全例
が180日以上の生存を見ている。またC1498細胞
を移植し、６日目からロイコシジン（5.0μg）を
１日おきに５回投与した群(C)では２例を除く８例
が180日以上の生存を見ている。Example Mouse myeloid leukemia therapeutic effect Mouse myeloid leukemia C1498 cells (5 x 10 4 cells/mouse) in C57BL/6 mice (female, 5-6 weeks old)
is injected into the jugular vein to create a system that causes death within two weeks. 24 hours after transplantation of C1498 cells, 5.0 μg of Staphylococcal leukocidin (a 1:1 mixture of leukocidin F and S) obtained in the reference example dissolved in saline was administered to each mouse via the jugular vein. The figure shows the survival rate of the mice in this case. In the figure, ↓ indicates a single administration (5.0 μg) of leukocidin, and when multiple doses were administered, all were administered every other day. The experiment consisted of 1 group of 10
Two mice were used. In the control group (A), only saline was administered in the same manner after C1498 cells were transplanted. As is clear from the figure, all cases in the control group died within 13 days after transplantation with C1498 cells;
After transplanting C1498 cells, leukocidin (5.0 μg) was added for 24 hours.
In the group (B) in which the drug was administered 4 times every other day from time 1, all cases survived for 180 days or more. In addition, in the group (C) in which C1498 cells were transplanted and leucocidin (5.0 μg) was administered five times every other day from day 6, all but two cases survived for 180 days or more.
実施例 １
あらかじめマンニトールで1000倍に希釈したロ
イコシジン50mgとマンニトール10ｇを注射用蒸留
水に溶解し1000mlとする。この液を無菌室内にて
無菌操作で0.22μmメンプランフイルターを用い
て過し滅菌した５ml容量のバイアル瓶1000本に
１mlずつ充填し常法により凍結乾燥した。Example 1 50 mg of leukocidin, previously diluted 1000 times with mannitol, and 10 g of mannitol are dissolved in distilled water for injection to make 1000 ml. This liquid was filled in 1 ml portions into 1,000 5 ml vials which had been sterilized by passing through a 0.22 μm Membrane filter in a sterile room and lyophilized using a conventional method.
凍結乾燥品は１瓶中にロイコシジン50ngを含
有する白色多孔質固体で、注射用蒸留水，注射用
生理食塩水に速かに澄明に溶解した。 The lyophilized product was a white porous solid containing 50 ng of leukocidin per bottle, and was quickly and clearly dissolved in distilled water for injection and physiological saline for injection.
実施例 ２
ロイコシジン10mgを常法によりトウモロコシデ
ンプン47ｇで希釈し均一な倍散にした後マンニト
ール442.79ｇと混合する。結合剤として12％ヒド
ロキシプロピルセルロース溶液60ｇを加えて練合
し、35meshの篩を通し造粒し乾燥した。乾燥物
にステアリン酸カルシウム３ｇを混合し35mesh
で篩過。直径５mmの平型金型を用いて１錠の重量
50mgで成形、１錠中ロイコシジン1μgを含有する
錠剤を製造した。Example 2 10 mg of leukocidin was diluted with 47 g of corn starch in a conventional manner to obtain a homogeneous powder, and then mixed with 442.79 g of mannitol. 60 g of 12% hydroxypropyl cellulose solution was added as a binder, the mixture was kneaded, passed through a 35 mesh sieve, and granulated and dried. Mix 3g of calcium stearate with dry material and make 35mesh
Pass through the sieve. Weight of one tablet using a flat mold with a diameter of 5 mm
Tablets containing 1 μg of leukocidin in 50 mg molded tablets were produced.
図面は骨髄性白血病細胞を注入したマウスにお
けるロイコシジンの延命効果を示したものであ
る。
The figure shows the survival effect of leukocidin on mice injected with myeloid leukemia cells.
Claims (1)
有する抗腫瘍剤。 ２ 腫瘍が骨髄性白血病、単球性白血病等の白血
病である特許請求の範囲第１項記載の抗腫瘍剤。 ３ 腫瘍がヒトの骨髄性白血病である特許請求の
範囲第１項記載の抗腫瘍剤。[Scope of Claims] 1. An antitumor agent containing staphylococcal leukocidin as an active ingredient. 2. The antitumor agent according to claim 1, wherein the tumor is leukemia such as myeloid leukemia or monocytic leukemia. 3. The antitumor agent according to claim 1, wherein the tumor is human myeloid leukemia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58023867A JPS59152331A (en) | 1983-02-17 | 1983-02-17 | Antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58023867A JPS59152331A (en) | 1983-02-17 | 1983-02-17 | Antitumor agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59152331A JPS59152331A (en) | 1984-08-31 |
| JPH0363533B2 true JPH0363533B2 (en) | 1991-10-01 |
Family
ID=12122388
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58023867A Granted JPS59152331A (en) | 1983-02-17 | 1983-02-17 | Antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59152331A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55139322A (en) * | 1979-04-13 | 1980-10-31 | Fujirebio Inc | Immunity enhancer |
| JPS5714533A (en) * | 1980-06-29 | 1982-01-25 | Koutaku Hayashi | Preparation for immunochemical therapy, prevention of drug resistance and anticancer |
-
1983
- 1983-02-17 JP JP58023867A patent/JPS59152331A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55139322A (en) * | 1979-04-13 | 1980-10-31 | Fujirebio Inc | Immunity enhancer |
| JPS5714533A (en) * | 1980-06-29 | 1982-01-25 | Koutaku Hayashi | Preparation for immunochemical therapy, prevention of drug resistance and anticancer |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59152331A (en) | 1984-08-31 |
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