JPH0597695A - Macrophage-activating composition - Google Patents
Macrophage-activating compositionInfo
- Publication number
- JPH0597695A JPH0597695A JP3280383A JP28038391A JPH0597695A JP H0597695 A JPH0597695 A JP H0597695A JP 3280383 A JP3280383 A JP 3280383A JP 28038391 A JP28038391 A JP 28038391A JP H0597695 A JPH0597695 A JP H0597695A
- Authority
- JP
- Japan
- Prior art keywords
- cyclodextrin
- macrophage
- macrophage activating
- composition
- activity
- 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
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明はマクロファージ活性化組
成物に関し、詳しくはマクロファージ活性化因子に特定
のサイクロデキストリンを配合してなるマクロファージ
活性化組成物に関する。TECHNICAL FIELD The present invention relates to a macrophage activating composition, and more particularly to a macrophage activating composition comprising a macrophage activating factor and a specific cyclodextrin.
【０００２】[0002]
【従来の技術及び発明が解決しようとする課題】マクロ
ファージは、インターロイキン１やＴＮＦなどのモノカ
インを生産するほか、遅延型アレルギー反応の発現な
ど、様々な生体防御のシステムに関与している。このマ
クロファージを活性化する作用を有する物質の存在も知
られており、エンドトキシンもその１つである。エンド
トキシンの本体はグラム陰性細菌表層のリポ多糖（lipo
polysaccharide；ＬＰＳ）であることが知られている
（代謝、vol.２６,No.５，１９８９）。このため、エン
ドトキシンの構造と活性の関係を研究して、より優れた
マクロファージ活性化因子を提供しようとする試みがな
されている。BACKGROUND OF THE INVENTION Macrophages produce monokines such as interleukin 1 and TNF, and are involved in various biological defense systems such as development of delayed allergic reaction. The existence of a substance having an action of activating this macrophage is also known, and endotoxin is one of them. The body of endotoxin is lipopolysaccharide (lipopolysaccharide) on the surface of Gram-negative bacteria.
It is known to be an LPS) (Metabolism, vol. 26, No. 5, 1989). Therefore, attempts have been made to study the relationship between endotoxin structure and activity to provide a better macrophage activating factor.
【０００３】一方、サイクロデキストリンは環状のオリ
ゴ糖であり、医薬品や食品などに添加して品質を安定に
するために用いられている。近年、β−サイクロデキス
トリンにはマウス腹腔マクロファージのスーパーオキサ
イド産生能増強効果があることが明らかにされた（炎
症、vol.１１,No.３, 1991年５月、２２５）。On the other hand, cyclodextrin is a cyclic oligosaccharide and is used for stabilizing the quality by adding it to medicines and foods. Recently, it was revealed that β-cyclodextrin has an effect of enhancing superoxide producing ability of mouse peritoneal macrophages (inflammation, vol. 11, No. 3, May 1991, 225).
【０００４】[0004]
【課題を解決するための手段】本発明者らはエンドトキ
シンなどのマクロファージ活性化因子の活性能を高める
目的で、特定のサイクロデキストリンを添加してみたと
ころ、有効であることを見出し、本発明を完成した。Means for Solving the Problems The present inventors have found that when a specific cyclodextrin was added for the purpose of enhancing the activity of macrophage activating factor such as endotoxin, the present invention was effective, completed.
【０００５】すなわち、本発明はマクロファージ活性化
因子にβ−サイクロデキストリンおよび／またはγ−サ
イクロデキストリンを配合してなるマクロファージ活性
化組成物を提供するものである。That is, the present invention provides a macrophage activating composition comprising a macrophage activating factor and β-cyclodextrin and / or γ-cyclodextrin.
【０００６】本発明に係るマクロファージ活性化因子と
しては特に制限はなく、例えばＬＰＳなどのエンドトキ
シンのほか、ＧＬＡ−６０，リピッドＡなどが挙げられ
る。The macrophage activating factor according to the present invention is not particularly limited, and examples thereof include endotoxins such as LPS, GLA-60, lipid A and the like.
【０００７】マクロファージ活性化因子に添加するサイ
クロデキストリンとしてはβ−サイクロデキストリンお
よびγ−サイクロデキストリンがあり、これらをそれぞ
れ単独で、または混合して使用できる。添加量はマクロ
ファージ活性化因子に対し、0.０１〜３重量％の割合で
加えることが必要である。サイクロデキストリンの添加
量が下限未満であると、十分な効果が得られず、上限を
越えると、充分な溶解性が得られないため、好ましくな
い。The cyclodextrins added to the macrophage activating factor include β-cyclodextrin and γ-cyclodextrin, and these can be used alone or in a mixture. It is necessary to add it in a proportion of 0.01 to 3% by weight with respect to the macrophage activating factor. If the amount of cyclodextrin added is less than the lower limit, a sufficient effect cannot be obtained, and if it exceeds the upper limit, sufficient solubility cannot be obtained, which is not preferable.
【０００８】本発明のマクロファージ活性化組成物を用
いてマクロファージを活性化するには、非経口的または
経口的に投与すればよい。非経口的に投与する場合、該
組成物を溶液または懸濁液として投与する。このときの
溶媒としては注射用水および生理食塩液などが適当であ
る。ヒトを含む哺乳動物における１日の投与量は体重１
ｋｇあたり５〜３００ｍｇ、好ましくは１０〜１００ｍ
ｇの範囲とすべきである。また、経口的に投与する場
合、該組成物を製薬上許容される賦形剤などと混合し、
所望によりゼラチンカプセルに入れて用いたり、該組成
物を澱粉，滑沢剤，賦形剤などと混合し有効成分が２０
〜２０００ｍｇ含まれるように調製して錠剤に打錠して
用いることができる。Macrophages can be activated using the macrophage activating composition of the present invention by parenteral or oral administration. When administered parenterally, the composition is administered as a solution or suspension. Water for injection and physiological saline are suitable as the solvent at this time. The daily dose in mammals including humans is 1
5 to 300 mg per kg, preferably 10 to 100 m
Should be in the range of g. When administered orally, the composition is mixed with a pharmaceutically acceptable excipient, etc.,
If desired, the composition may be used by encapsulating it in a gelatin capsule or mixing the composition with starch, lubricant, excipient, etc.
It may be prepared so as to contain ˜2000 mg and compressed into tablets for use.
【０００９】[0009]
【実施例】次に、本発明を実施例により詳しく説明す
る。 実施例１ ＢＡＬＢ／ｃ雌性マウスの腹腔内に2.４％チオグリコレ
ート２mlを注入し、４日後にマクロファージを含有する
腹水を採取した。得られた腹水から腹腔マクロファージ
を常法により遠心分離し、１％ＦＣＳを加えたＰＲＭＩ
１６４０培養液に２×１０5 cells/mlに遊離し、さらに
１ml／wellで３日間静止培養を行った。その後、上清を
除去し新たなＰＲＭＩ１６４０培養液を加え、さらにＬ
ＰＳ（E.coli, ０１２７：Ｂ８由来）0.５μｇ/ml およ
び各種糖類をそれぞれの濃度になるように加えた。添加
２０時間後、上清に存在するインターロイキン１活性
（リンパ球活性因子）を測定した。測定はRossenwaser
らの方法（Cell Immunol.,vol.６３，１３４，１９８
１）を用い、 3Ｈ−チミジンの取込み量を液体シンチレ
ーション・カウンターで測定することにより行った。EXAMPLES Next, the present invention will be described in more detail by way of examples. Example 1 2 ml of 2.4% thioglycolate was intraperitoneally injected into BALB / c female mice, and 4 days later, ascites fluid containing macrophages was collected. From the obtained ascites, peritoneal macrophages were centrifuged by a conventional method, and PRMI containing 1% FCS was added.
2 × 10 5 cells / ml were released in 1640 culture solution, and static culture was further performed at 1 ml / well for 3 days. After that, the supernatant was removed, and a new PRMI1640 culture solution was added.
PS (from E. coli, 0127: B8) 0.5 μg / ml and various sugars were added to each concentration. 20 hours after the addition, the interleukin 1 activity (lymphocyte activation factor) present in the supernatant was measured. Measured by Rossenwaser
Et al. (Cell Immunol., Vol. 63, 134, 198).
1) was used and the amount of 3 H-thymidine incorporated was measured by a liquid scintillation counter.
【００１０】結果は図１の通りである。α−サイクロデ
キストリンおよびグルコースにはＬＰＳによる腹腔マク
ロファージからのリンパ球活性因子の活性増強作用は認
められなかったが、β−サイクロデキストリンおよびγ
−サイクロデキストリンには添加濃度の0.１mg／ml以上
で著しい活性増強作用が認められた。The results are shown in FIG. Although α-cyclodextrin and glucose did not show the activity of LPS to enhance the activity of lymphocyte activating factor from peritoneal macrophages, β-cyclodextrin and γ
-Cyclodextrin showed a remarkable activity-enhancing effect at an addition concentration of 0.1 mg / ml or more.
【００１１】実施例２ 実施例１で得られた腹水から腹腔マクロファージを常法
により遠心分離し、１％ＦＣＳを加えたＰＲＭＩ１６４
０培養液に２×１０5 cells/mlに浮遊し、さらに１ml/w
ell で３日間静止培養を行った。その後、上清を除去し
新たなＰＲＭＩ１６４０培養液を加え、さらに上記ＬＰ
Ｓ５０μｇ/ml および各種糖類をそれぞれの濃度になる
ように加えた。添加２０時間後、上清に存在するインタ
ーロイキン１活性（リンパ球活性因子）を実施例１と同
様にして測定した。Example 2 From the ascites obtained in Example 1, peritoneal macrophages were centrifuged by a conventional method, and PRMI164 containing 1% FCS was added.
Suspended at 2 × 10 5 cells / ml in culture medium 0, and further 1 ml / w
Cell culture was carried out in ell for 3 days. After that, the supernatant was removed, a new PRMI1640 culture solution was added, and the LP
S50 μg / ml and various sugars were added to each concentration. 20 hours after the addition, the interleukin 1 activity (lymphocyte activation factor) present in the supernatant was measured in the same manner as in Example 1.
【００１２】結果は図２の通りであり、α−サイクロデ
キストリンおよびグルコースにはＬＰＳによる腹腔マク
ロファージからのリンパ球活性因子の活性増強作用は認
められなかったが、β−サイクロデキストリンおよびγ
−サイクロデキストリンには添加濃度0.１mg／ml以上で
軽度ながら活性増強作用が認められた。The results are shown in FIG. 2. Although α-cyclodextrin and glucose were not found to have the activity of enhancing the activity of lymphocyte activating factor from peritoneal macrophages by LPS, β-cyclodextrin and γ.
-Cyclodextrin had a slight activity-enhancing effect at an addition concentration of 0.1 mg / ml or more.
【００１３】[0013]
【発明の効果】本発明によれば、マクロファージ活性化
因子にβ−サイクロデキストリンおよび／またはγ−サ
イクロデキストリンを配合してなるマクロファージ活性
化組成物が提供される。この組成物は安全性が高く、か
つマクロファージを効率的に活性化する作用を有してい
る。According to the present invention, there is provided a macrophage activating composition comprising a macrophage activating factor and β-cyclodextrin and / or γ-cyclodextrin. This composition is highly safe and has the effect of efficiently activating macrophages.
【図１】 マウスに対し、ＬＰＳ 0.５μｇ／mlおよび
各種糖類を加えた場合のインターロイキン１活性を示
す。FIG. 1 shows interleukin 1 activity when LPS 0.5 μg / ml and various sugars were added to mice.
【図２】 マウスに対し、ＬＰＳ ５０μｇ／mlおよび
各種糖類を加えた場合のインターロイキン１活性を示
す。FIG. 2 shows interleukin 1 activity in the case of adding 50 μg / ml of LPS and various sugars to mice.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 中野 一郎 東京都江戸川区東葛西５−28−３ クリー ンエノモト105 (72)発明者 柱 新太郎 東京都北区上十条３−９−13 丸星マンシ ヨン203 (72)発明者 藤井 良知 東京都中野区東中野２−33−２ ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Ichiro Nakano 5-28-3 Higashikasai, Edogawa-ku, Tokyo 105 Clean Enomoto 105 (72) Inventor Shintaro Pila 3-9-13 Kamijujo, Kita-ku, Tokyo Maruhoshi Mansion 203 (72) Inventor Yoshitomo Fujii 2-33-2 Higashi-Nakano, Nakano-ku, Tokyo
Claims (3)
ロデキストリンおよび／またはγ−サイクロデキストリ
ンを配合してなるマクロファージ活性化組成物。1. A macrophage activating composition comprising a macrophage activating factor and β-cyclodextrin and / or γ-cyclodextrin.
キシン，ＧＬＡ−６０およびリピッドＡのいずれかであ
る請求項１記載のマクロファージ活性化組成物。2. The macrophage activating composition according to claim 1, wherein the macrophage activating factor is any one of endotoxin, GLA-60 and lipid A.
ロデキストリンおよび／またはγ−サイクロデキストリ
ンを0.０１〜３重量％の割合で配合した請求項１記載の
マクロファージ活性化組成物。3. The macrophage activating composition according to claim 1, wherein β-cyclodextrin and / or γ-cyclodextrin is added to the macrophage activating factor in a proportion of 0.01 to 3% by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3280383A JP2772878B2 (en) | 1991-10-02 | 1991-10-02 | Macrophage activating composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3280383A JP2772878B2 (en) | 1991-10-02 | 1991-10-02 | Macrophage activating composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0597695A true JPH0597695A (en) | 1993-04-20 |
| JP2772878B2 JP2772878B2 (en) | 1998-07-09 |
Family
ID=17624259
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3280383A Expired - Fee Related JP2772878B2 (en) | 1991-10-02 | 1991-10-02 | Macrophage activating composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2772878B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7449301B2 (en) | 2004-04-28 | 2008-11-11 | National University Corporation Gunma University | Pharmaceutical composition and method for activating macrophage using the same |
| WO2013038997A1 (en) | 2011-09-14 | 2013-03-21 | 医療法人再生未来 | Pharmaceutical composition and manufacturing method therefor |
| WO2015087981A1 (en) | 2013-12-13 | 2015-06-18 | 医療法人再生未来 | Bovine colostrum enzyme processed product, production method therefor, composition, and food or beverage |
| KR20180013981A (en) | 2015-06-01 | 2018-02-07 | 사이세이 파마 씨오., 엘티디. | Milk enzyme-treated water, its production method, composition and product |
-
1991
- 1991-10-02 JP JP3280383A patent/JP2772878B2/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7449301B2 (en) | 2004-04-28 | 2008-11-11 | National University Corporation Gunma University | Pharmaceutical composition and method for activating macrophage using the same |
| WO2013038997A1 (en) | 2011-09-14 | 2013-03-21 | 医療法人再生未来 | Pharmaceutical composition and manufacturing method therefor |
| US8747919B2 (en) | 2011-09-14 | 2014-06-10 | Saisei Mirai Clinic | Pharmaceutical composition and method of preparing same |
| US9409972B2 (en) | 2011-09-14 | 2016-08-09 | Tokushima University | Pharmaceutical composition and method of preparing same |
| US9670268B2 (en) | 2011-09-14 | 2017-06-06 | Saisei Mirai Clinic | Pharmaceutical composition and method of preparing same |
| WO2015087981A1 (en) | 2013-12-13 | 2015-06-18 | 医療法人再生未来 | Bovine colostrum enzyme processed product, production method therefor, composition, and food or beverage |
| KR20160096089A (en) | 2013-12-13 | 2016-08-12 | 사이세이 파마 씨오., 엘티디. | Bovine colostrum enzyme processed product, production method therefor, composition, and food or beverage |
| US10322147B2 (en) | 2013-12-13 | 2019-06-18 | Saisei Pharma Co., Ltd. | Enzyme-treated bovine colostrum, preparation method thereof, composition, and foods and beverages |
| KR20180013981A (en) | 2015-06-01 | 2018-02-07 | 사이세이 파마 씨오., 엘티디. | Milk enzyme-treated water, its production method, composition and product |
| US11464835B2 (en) | 2015-06-01 | 2022-10-11 | Saisei Pharma Co., Ltd. | Enzyme-treated milk product, preparation method thereof, composition, and products |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2772878B2 (en) | 1998-07-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |