JPS63152327A - Immune activating agent and anticancer agent containing hemolysis preventing composition consisting of fat emulsion - Google Patents
Immune activating agent and anticancer agent containing hemolysis preventing composition consisting of fat emulsionInfo
- Publication number
- JPS63152327A JPS63152327A JP62293142A JP29314287A JPS63152327A JP S63152327 A JPS63152327 A JP S63152327A JP 62293142 A JP62293142 A JP 62293142A JP 29314287 A JP29314287 A JP 29314287A JP S63152327 A JPS63152327 A JP S63152327A
- Authority
- JP
- Japan
- Prior art keywords
- fat emulsion
- anticancer agent
- lysophospholipids
- immunostimulant
- hemolysis
- 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
- 239000002960 lipid emulsion Substances 0.000 title claims abstract description 29
- 239000000203 mixture Substances 0.000 title claims abstract description 29
- 206010018910 Haemolysis Diseases 0.000 title claims abstract description 22
- 230000008588 hemolysis Effects 0.000 title claims abstract description 22
- 239000002246 antineoplastic agent Substances 0.000 title claims description 17
- 239000003795 chemical substances by application Substances 0.000 title abstract description 7
- 230000003213 activating effect Effects 0.000 title 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 18
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 235000011187 glycerol Nutrition 0.000 claims abstract description 9
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 8
- 230000003308 immunostimulating effect Effects 0.000 claims description 19
- 229960001438 immunostimulant agent Drugs 0.000 claims description 16
- 239000003022 immunostimulating agent Substances 0.000 claims description 16
- 239000003549 soybean oil Substances 0.000 claims description 6
- 235000012424 soybean oil Nutrition 0.000 claims description 6
- 239000008344 egg yolk phospholipid Substances 0.000 claims description 5
- 229940068998 egg yolk phospholipid Drugs 0.000 claims description 5
- 239000003921 oil Substances 0.000 claims description 3
- 235000019198 oils Nutrition 0.000 claims description 3
- MHFRGQHAERHWKZ-UHFFFAOYSA-N 1-octadecyl-2-methylglycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCCOCC(OC)COP([O-])(=O)OCC[N+](C)(C)C MHFRGQHAERHWKZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- 239000007924 injection Substances 0.000 abstract description 7
- 238000002347 injection Methods 0.000 abstract description 7
- 238000001990 intravenous administration Methods 0.000 abstract description 4
- 229950004354 phosphorylcholine Drugs 0.000 abstract 1
- 230000002949 hemolytic effect Effects 0.000 description 18
- 239000000126 substance Substances 0.000 description 12
- 238000009472 formulation Methods 0.000 description 8
- 239000003708 ampul Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 239000003925 fat Substances 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 239000000787 lecithin Substances 0.000 description 4
- 235000010445 lecithin Nutrition 0.000 description 4
- 229940067606 lecithin Drugs 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 235000014593 oils and fats Nutrition 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- 240000002791 Brassica napus Species 0.000 description 1
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、脂肪乳剤から成る溶血防止用組成物を含有す
る免疫賦活剤および制癌剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an immunostimulant and an anticancer agent containing a composition for preventing hemolysis consisting of a fat emulsion.
［従来の技術］
一般に、血液中に溶血性物質といわれる物質の存在によ
り、赤血球が溶血するという現象のあることが知られて
いる。上記した溶血性物質としては種々の物質があるが
、その中で、たとえば、リゾリン脂質類の如く、溶血性
のみならず他の生理的に有用な作用（たとえば、制癌作
用および免疫賦活作用など〉を有する物質もあり、その
利用が期待されるものである。従来、これら溶血性物質
の有する溶血作用を減少させる物質はいくつかくたとえ
ば、コレステロールなど）知られているが、これらはそ
の物質自体の安全性に問題があり、更に、溶血作用のみ
ならず、溶血性物質の有する他の全ての作用をも弱化せ
しめる。従って、安全性が高くかつ溶血作用を選択的に
弱化せしめるものは、従来知られていなかった。[Prior Art] It is generally known that the presence of a substance called a hemolytic substance in blood causes hemolysis of red blood cells. There are various hemolytic substances mentioned above, and among them, for example, lysophospholipids have not only hemolytic properties but also other physiologically useful effects (e.g., anticancer effect, immunostimulatory effect, etc.). There are some substances that have the following properties, and their use is expected. Some substances have been known to reduce the hemolytic effect of these hemolytic substances (for example, cholesterol), but these substances themselves There is a problem with the safety of hemolytic substances, and furthermore, they weaken not only the hemolytic effect but also all other effects of hemolytic substances. Therefore, there has been no known substance that is highly safe and selectively weakens the hemolytic effect.
［発明が解決しようとする問題点］
かかる状況下において、本発明者らは生理的に有用な作
用（たとえば、制癌作用および免疫賦活作用など）に影
響せず、溶血作用のみを減少せしめる作用を有し、その
物質自体高い安全性を有する薬剤を見出さんと鋭意研究
した。[Problems to be Solved by the Invention] Under such circumstances, the present inventors have developed an action that reduces only the hemolytic action without affecting physiologically useful actions (for example, anticancer action and immunostimulatory action). We conducted intensive research to find a drug that has a high level of safety and that the substance itself is highly safe.
［問題点を解決するための手段］
従来、栄養失調症、外科手術前後もしくは伝染病の回復
期などの場合に総合栄養剤または輸液としてのみその使
用法が知られている脂肪乳剤がリゾリン脂質類などの溶
血性物質の有する溶血作用を減少せしめる作用を有する
こと、更には、リゾリン脂質類などの有する免疫賦活作
用および制癌作用にはほとんど影響せず、溶血作用を選
択的に減少させ、脂肪乳剤を含有する免疫賦活剤および
制癌剤は安全性が高いことを見出し、本発明を完成した
。[Means for solving the problem] Lysophospholipids are fat emulsions that have been known to be used only as comprehensive nutritional supplements or infusions in cases of malnutrition, before and after surgery, or during the recovery period from an infectious disease. It has the effect of reducing the hemolytic effect of hemolytic substances such as The present invention was completed based on the discovery that immunostimulants and anticancer agents containing emulsions are highly safe.
即ち、本発明は脂肪乳剤から成る溶血防止用組成物を含
有する免疫賦活剤および制癌剤を提供するものである。That is, the present invention provides an immunostimulant and an anticancer agent containing a composition for preventing hemolysis consisting of a fat emulsion.
以下、本発明について詳述する。The present invention will be explained in detail below.
脂肪乳剤から成る溶血防止用組成物は、油脂、乳化剤お
よび水を基本的な構成４分とし、ざらに、等張化剤、抗
酸化剤または製剤上許容される添加剤などを適宜添加さ
れていてもよく、油脂としては、たとえば、大豆油、ゴ
マ油、綿実油、ココナツト油、トウモロコシ油または落
花生油などの食用あるいは医薬用油脂が挙げられ、乳化
剤としては、たとえば、大豆、綿実油、ナタネ、トウモ
ロコシもしくは卵黄など天然由来のリン脂質またはレシ
チンもしくは合成されたレシチンなどが挙げられ、特に
天然由来のリン脂質は、レシチン、ホスファチジルエタ
ノールアミン、ホスファチジルセリン、ホスファチジル
イノシトールおよびスフィンゴミエリンなどのリン脂質
から成り、本発明に使用する場合には、そのまま用いて
もよいし、レシチンの含有率を高めるために精製された
ものを用いてもよく、ざらにこれらを水素添加して飽和
型リン脂質として用いてもよい。また、等張化剤として
は、グリセリン、ソルビトールまたはキシリトールなど
が挙げられ、抗酸化剤としては、トコフェロールなどが
挙げられ、製剤１許されるならばデキストランまたはメ
チオニンなどの添加剤を添加してもよい。A composition for preventing hemolysis consisting of a fat emulsion has a basic composition of oil, fat, emulsifier, and water, and may contain an isotonizing agent, an antioxidant, or additives acceptable for the formulation as appropriate. The oils and fats include, for example, edible or medicinal oils and fats such as soybean oil, sesame oil, cottonseed oil, coconut oil, corn oil, and peanut oil, and the emulsifiers include, for example, soybean, cottonseed oil, rapeseed, corn or Naturally derived phospholipids such as egg yolk or lecithin or synthetic lecithin may be mentioned, and in particular, naturally derived phospholipids consist of phospholipids such as lecithin, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin, and the present invention When used in phospholipids, they may be used as they are, or may be purified to increase the lecithin content, or may be roughly hydrogenated and used as saturated phospholipids. In addition, examples of isotonizing agents include glycerin, sorbitol, or xylitol, and examples of antioxidants include tocopherol. If permitted in Formulation 1, additives such as dextran or methionine may be added. .
また、上記した基本的構成４分の混合割合は、特に限定
されないが、油脂１０に対し、重量比で水５．０〜２０
０および乳化剤０．１〜５．０であればよく、好ましく
は乳化剤０２１〜１．５である方がよい。現在、イント
ラファツトまたはインドラリピッド（登録商標）などと
して市販されている大豆油１０に対して重量比でグリセ
リン？、５、卵黄リン脂質１．２および水８６．３から
成る脂肪乳剤を、あるいは７ Ｆ ”）トグン（登録商
標） 、Ｌｉｐｏｆｕｎｄｉｎ−３（ドイツ国、Ｂｒａ
ＬＩｎ Ｌｌｅｌｓｕｎｑｅｎ社品） 、Ｌｉｐｉｈｙ
ｓａｎ （フランス国、Ｅｇｉｃ社品）などを直接使
用に供してもよい。本発明の脂肪乳剤から成る溶血防止
用組成物を含有する免疫賦活剤および制癌剤は、上記で
説明した脂肪乳剤から成る溶血防止用組成物とリゾリン
脂質類から成る免疫賦活剤および制癌剤であり、リゾリ
ン脂質類としては、たとえば、下に示す一般式［Ｉ］で
表わされるリゾリン脂質類が挙げられる。In addition, the mixing ratio of the above-mentioned basic composition of 4 parts is not particularly limited, but the weight ratio of water to 10 parts of oil and fat is 5.0 to 20 parts.
0 and emulsifier 0.1 to 5.0, preferably emulsifier 021 to 1.5. What is the weight ratio of glycerin to 10 parts of soybean oil, which is currently commercially available as Intrafat or Indoralipid (registered trademark)? , 5, a fat emulsion consisting of 1.2 egg yolk phospholipids and 86.3 water, or 7 F'') Togun®, Lipofundin-3 (Bra, Germany).
LIn Lelsunqen product), Lipihy
san (manufactured by Egic, France) or the like may be used directly. The immunostimulant and anticancer agent containing the composition for preventing hemolysis comprising the fat emulsion of the present invention is an immunostimulant and anticancer agent comprising the composition for preventing hemolysis comprising the fat emulsion described above and lysophospholipids. Examples of the lipids include lysophospholipids represented by the general formula [I] shown below.
（式中、Ｒ１はアシルオキシ基またはアルコキシ基を、
Ｒ２はヒドロキシル基または低級アルコキシ基を、Ｒ３
は水素原子または低級アルキル基を表わす。なお、Ｒ１
とＲ２は相互に交換しうる。）そして、好ましくは一般
式［Ｉ］で表わされるリゾリン脂質類がリゾレシチン（
［１１式中、Ｒ＝Ｃアルカノイルオキシ
１４〜 １８
ヒドロキシル基およびＲ３−メチル基）もしくはエーテ
ル型リゾレシチンである１−オクタデシル−２−メチル
−グリセロ−３−ホスホリルコリンなとであることが望
ましい。更に一般式［Ｉ］で表わされる化合物には、通
常、Ｄ．ＬおよびＤし体が存在するが、本発明はそのい
ずれも包含する。(In the formula, R1 is an acyloxy group or an alkoxy group,
R2 is a hydroxyl group or a lower alkoxy group, R3
represents a hydrogen atom or a lower alkyl group. In addition, R1
and R2 are interchangeable. ) Preferably, the lysophospholipid represented by the general formula [I] is lysolecithin (
[In formula 11, R=C alkanoyloxy 14-18 hydroxyl group and R3-methyl group] or 1-octadecyl-2-methyl-glycero-3-phosphorylcholine, which is an ether type lysolecithin, is preferable. Furthermore, the compound represented by the general formula [I] usually includes D. L and D forms exist, both of which are included in the present invention.
本発明の溶血防止用組成物を含有する免疫賦活剤および
制癌剤を得るには、脂肪乳剤から成る溶血防止用組成物
に、リゾリン脂質類の粉末を添加して使用してもよいし
、生理用食塩水などに溶解させたりプリン脂質類のアン
プル溶液を添加して使用してもよい。In order to obtain an immunostimulant and an anticancer agent containing the composition for preventing hemolysis of the present invention, powder of lysophospholipids may be added to the composition for preventing hemolysis consisting of a fat emulsion, or a sanitary It may be used by dissolving it in a saline solution or by adding an ampoule solution of purine lipids.
更に、本発明の溶血防止用組成物を含有する免疫賦活剤
および制癌剤には、使用または製剤化のために通常、当
該分野で知られている添加剤を使用してもよい。このよ
うに調製された脂肪乳剤から成る溶血防止用組成物を含
有する免疫賦活剤および制癌剤を患者に投与する場合、
その投与経路、投与回数および投与量は、一般に患者の
症状に応じて適宜最適条件が選択されるが、通常は成人
−日当タリ、リゾリン脂質類（０．１ 〜２００ ｍ’
ｌ／ＫＦＩ”）Ｘ（’ｌ〜４回）およびリゾリン脂質類
が溶血作用を併起しない量の脂肪乳剤を含有する薬剤を
注射、特に静脈点滴で投与するのが好ましい。Furthermore, the immunostimulant and anticancer agent containing the composition for preventing hemolysis of the present invention may contain additives commonly known in the art for use or formulation. When administering to a patient an immunostimulant and an anticancer agent containing a composition for preventing hemolysis consisting of a fat emulsion prepared in this way,
The route of administration, number of administrations, and dosage are generally selected to suit the patient's symptoms, but usually the daily dose for adults, lysophospholipids (0.1 to 200 m'
It is preferable to administer a drug containing a fat emulsion in an amount that does not cause hemolytic effects and lysophospholipids to be administered by injection, especially by intravenous drip.
［発明の効果］ つぎに薬理効果について述べる。[Effect of the invention] Next, we will discuss the pharmacological effects.
（イ）溶血性
溶血性は、家兎赤血球浮遊液と被検薬剤（リゾレシチン
または脂肪乳剤およびリゾレシチンの混合物）を混合し
、３７℃で１時間振盪させ遠沈上清の５５０ｍμにおけ
る吸光度（以下０．Ｄ．と記す）を測定し、蒸留水で完
全溶血した場合の吸光度を１００％として、５０％溶血
の場合の被検薬剤濃度をもって溶血性の程度の指標とし
た。また、Ｏ．Ｄ。(b) Hemolytic Hemolytic property was determined by mixing the rabbit red blood cell suspension and the test drug (lysolecithin or a mixture of fat emulsion and lysolecithin), shaking it at 37°C for 1 hour, and then centrifuging the supernatant at 550 mμ (absorbance of 0.D ) was measured, and the absorbance when complete hemolysis with distilled water was taken as 100%, and the test drug concentration at 50% hemolysis was used as an index of the degree of hemolysis. Also, O. D.
で測定できない場合は、肉眼判定をもってその溶血性を
（十）、クー）で表わした。その結果を表−１および２
に記す。If it was not possible to measure the hemolytic property with the naked eye, it was expressed as (10) or (10). The results are shown in Tables 1 and 2.
It is written in
表−１
（以下余白）
＝ ９ −
脂肪乳剤とリゾレシチン濃度との溶血性（リゾレシチン
：１アンプル２０ｍｇ／２威を基準に検討した）
十：溶血 士ニ一部溶血 −：非溶血
上の表−１および２から明らかなごとく、脂肪乳剤から
成る溶血防止用組成物が溶血作用を格段に減少させる作
用を有することがわかる。Table 1 (blank below) = 9 - Hemolytic properties of fat emulsion and lysolecithin concentration (studyed based on lysolecithin: 1 ampoule 20 mg/2 ml) 10: Hemolysis Partial hemolysis -: Non-hemolytic table - As is clear from 1 and 2, it can be seen that the composition for preventing hemolysis consisting of a fat emulsion has the effect of significantly reducing the hemolytic effect.
（口）制癌作用
（Ｉ） Ｌ−１２１０に対する前投与効果（Ｌ−１２１
０ａｌｌｏｇｒａｆｔ ）
ｄｄＮ系雄性マウスに被検薬剤（リゾレシチンおよび脂
肪乳剤とりゾレシチンの混合物）をそれぞれリゾレシチ
ン換算４０ｍｙ／Ｋｇで腹腔内に７日間適役した後、１
週間体薬後、Ｌ−１２１０白血病細胞を１×１０６個腹
腔内に接種し、その平均生存日数を求めた。その結果を
表−３に示す。(Mouth) Anticancer effect (I) Pre-administration effect on L-1210 (L-121
0allograft) Test drugs (lysolecithin and a mixture of fat emulsion and solecithin) were administered intraperitoneally to ddN male mice at a concentration of 40 my/Kg in terms of lysolecithin for 7 days.
After one week of systemic therapy, 1 x 106 L-1210 leukemia cells were inoculated intraperitoneally, and the average survival days were determined. The results are shown in Table-3.
表−３
＊リゾレシチン４０＃１ｇ／／（ｇ
＊＊リゾレシチン４０ｍｊｊ／Ｋｇ十脂肪乳剤２０ｍ！
ｊ／Ｋｇ脂肪乳剤の組成 大豆油 １０
（重量比） グリセリン ２．５卵黄リン脂質
１．２
水 ８６，３
（■）ルイス肺癌腫転位抑制効果
ルイス肺癌約１×１０６個をＢＤＦ１系雌性マウスに静
脈内投与し、２４時間後よりリゾレシチン（４０／／Ｉ
ｇ／ｌ（ｇ）を腹腔内に、また、脂肪乳剤（２０ｄ／Ｋ
ｇ）とリゾレシチン（４０ｍｙ／Ｋｙ）の混合物を静脈
内に、それぞれ１０日間連浸し、１１日目に開胸して無
処置マウスに対する肺の乾燥重量 ＜ｍｇ ｍｅａｎ
＋ｓ、 Ｅ、 ）を測定し、コントロール群とのＴ／Ｃ
でその抑制効果を求めた。その結果を表−４に示す。Table-3 *Lysolecithin 40#1g//(g **Lysolecithin 40mjj/Kg ten fat emulsion 20m!
Composition of j/Kg fat emulsion Soybean oil 10 (weight ratio) Glycerin 2.5 Egg yolk phospholipid
1.2 Water 86,3 (■) Effect of suppressing Lewis lung carcinoma metastasis Approximately 1 x 106 Lewis lung carcinomas were intravenously administered to BDF1 female mice, and 24 hours later, lysolecithin (40//I
g/l (g) intraperitoneally, and fat emulsion (20 d/K
A mixture of g) and lysolecithin (40 my/Ky) was intravenously infused for 10 days each, and on the 11th day, the chest was opened and the dry weight of the lungs of untreated mice was < mg mean
+s, E, ) and T/C with the control group.
The suppressive effect was determined. The results are shown in Table 4.
表−４
上の表−３および４から明らかなごとく、脂肪乳剤から
成る溶血防止用組成物およびリゾリン脂質類の代表的化
合物であるリゾレシチンを含有する免疫賦活剤および制
癌剤がリゾレシチンの免疫賦活作用および制癌作用に対
して、はとんど影響していないことがわかる。Table 4 As is clear from Tables 3 and 4 above, the composition for preventing hemolysis consisting of a fat emulsion and the immunostimulant and anticancer agent containing lysolecithin, which is a representative compound of lysophospholipids, have the immunostimulatory effect of lysolecithin. It can be seen that it has almost no effect on the anticancer effect.
［実施例］
つぎに本発明を参考製剤例および代表的な製剤例を挙げ
て説明する。[Example] Next, the present invention will be explained by giving reference formulation examples and representative formulation examples.
参考製剤例１
大豆油２０ｇ、脳グリセリン５．０ｇおよび卵黄リン脂
質２．４ｇの混合物に、水を液量が２００ ｒＩｄ；！
になるまで添加し、十分撹拌して、脂肪乳剤を得る。Reference Formulation Example 1 Add water to a mixture of 20 g of soybean oil, 5.0 g of brain glycerin, and 2.4 g of egg yolk phospholipid to a liquid volume of 200 rId;!
Add the fat until it becomes saturated and stir thoroughly to obtain a fat emulsion.
製剤例１
滅菌したＬ−リゾレシチン１．０ｇを注射用生理食塩水
１００ ｄに溶解した後、無菌濾過し、２ｄの注射用ア
ンプルに封入した注射剤を得る。Formulation Example 1 After dissolving 1.0 g of sterilized L-lysolecithin in 100 d of physiological saline for injection, it is sterile filtered to obtain an injection sealed in a 2 d ampoule for injection.
また、これと別に調製された脂肪乳剤（大豆油２０９、
濃グリセリン５．０ｇおよび卵黄リン脂質２．４９から
成る２００ｄ水溶液）に、前記した注開用アンプル溶液
を目的に応じて１０本分まで添加し、２〜３回振盪して
静注点滴剤とする。In addition, a separately prepared fat emulsion (soybean oil 209,
Depending on the purpose, add up to 10 ampoules of the above-mentioned injection ampule solution to a 200 d aqueous solution consisting of 5.0 g of concentrated glycerin and 2.49 g of egg yolk phospholipid, and shake 2 to 3 times to prepare an intravenous infusion. do.
製剤例２
市販の脂肪乳剤イントラファツト注５００ ｄに、Ｌ−
リゾレシチン２００ ｍｇを注射用生理食塩水２０威に
封入したく無菌濾過済）点滴用アンプル液を添加し、２
〜３回振盪して静注点滴剤とする。Formulation Example 2 L-
Add 200 mg of lysolecithin to 200 mg of physiological saline for injection, add sterile-filtered ampoule solution for infusion,
Shake ~3 times to prepare an intravenous drip.
Claims (7)
質類を含有する免疫賦活剤および制癌剤。(1) An immunostimulant and an anticancer agent containing a composition for preventing hemolysis consisting of a fat emulsion and lysophospholipids.
を構成々分とする脂肪乳剤である特許請求の範囲第（１
）項記載の免疫賦活剤および制癌剤。(2) Claim No. 1, wherein the fat emulsion is a fat emulsion containing oil, glycerin, phospholipid, and water as constituent components.
) The immunostimulant and anticancer agent described in section ).
〜２００、グリセリン０．５〜５．０およびリン脂質０
．１〜５．０を混合して成る脂肪乳剤である特許請求の
範囲第（２）項記載の免疫賦活剤および制癌剤。(3) Fat emulsion has a weight ratio of 5.0 water to 10 fat.
~200, glycerin 0.5-5.0 and phospholipid 0
．． The immunostimulant and anticancer agent according to claim (2), which is a fat emulsion obtained by mixing 1 to 5.0.
．３、グリセリン２．５および卵黄リン脂質１．２を混
合して成る脂肪乳剤である特許請求の範囲第（３）項記
載の免疫賦活剤および制癌剤。(4) Fat emulsion has a weight ratio of 86 parts water to 10 parts soybean oil.
．． 3. The immunostimulant and anticancer agent according to claim (3), which is a fat emulsion prepared by mixing 2.5 parts of glycerin and 1.2 parts of egg yolk phospholipid.
範囲第（１）〜（４）項いずれかの項記載の免疫賦活剤
および制癌剤。(5) The immunostimulant and anticancer agent according to any one of claims (1) to (4), wherein the lysophospholipid is lysolecithin.
求の範囲第（５）項記載の免疫賦活剤および制癌剤。(6) The immunostimulant and anticancer agent according to claim (5), wherein the lysophospholipid is L-lysolecithin.
−グリセロ−３−ホスホリルコリンである特許請求の範
囲第（１）〜（４）項いずれかの項記載の免疫賦活剤お
よび制癌剤。(7) The immunostimulant and anticancer agent according to any one of claims (1) to (4), wherein the lysophospholipid is 1-octadecyl-2-methyl-glycero-3-phosphorylcholine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62293142A JPS63152327A (en) | 1987-11-20 | 1987-11-20 | Immune activating agent and anticancer agent containing hemolysis preventing composition consisting of fat emulsion |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62293142A JPS63152327A (en) | 1987-11-20 | 1987-11-20 | Immune activating agent and anticancer agent containing hemolysis preventing composition consisting of fat emulsion |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2460079A Division JPS55118419A (en) | 1979-03-05 | 1979-03-05 | Antihemolytic composition consisting of fat emulsion and immunizator and carcinostatic agent containing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63152327A true JPS63152327A (en) | 1988-06-24 |
| JPS6410499B2 JPS6410499B2 (en) | 1989-02-22 |
Family
ID=17790967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62293142A Granted JPS63152327A (en) | 1987-11-20 | 1987-11-20 | Immune activating agent and anticancer agent containing hemolysis preventing composition consisting of fat emulsion |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63152327A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6277888B1 (en) | 1997-02-27 | 2001-08-21 | Welfide Corporation | Drug composition |
| JP2002513773A (en) * | 1998-05-07 | 2002-05-14 | コリクサ コーポレイション | Adjuvant composition and use thereof |
| JP2007176868A (en) * | 2005-12-28 | 2007-07-12 | Nagase Chemtex Corp | beta-GLUCURONIDASE INHIBITOR |
| KR100842159B1 (en) | 2002-03-25 | 2008-06-27 | 주식회사 바이오시너젠 | Composition for preventing and treating acute respiratory distress syndrome and multiple organ dysfunction syndrome comprising lysophosphatidylcholine or its derivatives |
| KR100849448B1 (en) * | 2002-08-22 | 2008-07-30 | 주식회사 바이오시너젠 | Composition for improving innate immunity comprising lysophosphatidylcholine and its derivatives |
| WO2015152412A1 (en) * | 2014-04-04 | 2015-10-08 | 国立大学法人大阪大学 | Drug delivery promoter containing substance for activating lysophospholipid receptors |
| WO2017057643A1 (en) * | 2015-09-29 | 2017-04-06 | 国立大学法人大阪大学 | Leukocyte infiltration promoter and tumor immunoactivator |
-
1987
- 1987-11-20 JP JP62293142A patent/JPS63152327A/en active Granted
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6277888B1 (en) | 1997-02-27 | 2001-08-21 | Welfide Corporation | Drug composition |
| EP2030614A1 (en) * | 1997-02-27 | 2009-03-04 | Novartis AG | Pharmaceutical Composition comprising 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol and a lecithin |
| JP2002513773A (en) * | 1998-05-07 | 2002-05-14 | コリクサ コーポレイション | Adjuvant composition and use thereof |
| KR100842159B1 (en) | 2002-03-25 | 2008-06-27 | 주식회사 바이오시너젠 | Composition for preventing and treating acute respiratory distress syndrome and multiple organ dysfunction syndrome comprising lysophosphatidylcholine or its derivatives |
| KR100849448B1 (en) * | 2002-08-22 | 2008-07-30 | 주식회사 바이오시너젠 | Composition for improving innate immunity comprising lysophosphatidylcholine and its derivatives |
| JP2007176868A (en) * | 2005-12-28 | 2007-07-12 | Nagase Chemtex Corp | beta-GLUCURONIDASE INHIBITOR |
| WO2015152412A1 (en) * | 2014-04-04 | 2015-10-08 | 国立大学法人大阪大学 | Drug delivery promoter containing substance for activating lysophospholipid receptors |
| JPWO2015152412A1 (en) * | 2014-04-04 | 2017-04-13 | 国立大学法人大阪大学 | Drug delivery accelerator containing substance that activates lysophospholipid receptor |
| WO2017057643A1 (en) * | 2015-09-29 | 2017-04-06 | 国立大学法人大阪大学 | Leukocyte infiltration promoter and tumor immunoactivator |
| CN108136020A (en) * | 2015-09-29 | 2018-06-08 | 国立大学法人大阪大学 | Leukocyte infiltration accelerating agent and tumour immunity activator |
| JPWO2017057643A1 (en) * | 2015-09-29 | 2018-08-16 | 国立大学法人大阪大学 | Leukocyte infiltration promoter and tumor immune activator |
| AU2016329670B2 (en) * | 2015-09-29 | 2019-12-12 | Osaka University | Leukocyte infiltration promoting agent and antitumor immunostimulatory agent |
| JP2020073572A (en) * | 2015-09-29 | 2020-05-14 | 国立大学法人大阪大学 | Leukocyte infiltration promoter and tumor immunoactivator |
| US11033559B2 (en) | 2015-09-29 | 2021-06-15 | Osaka University | Leukocyte infiltration promoting agent and antitumor immunostimulatory agent |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6410499B2 (en) | 1989-02-22 |
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