JPH0696636B2 - 2,4-bis (o-methoxypolyethylene glycol) -6-cholesteryl-S-triazine compound - Google Patents
2,4-bis (o-methoxypolyethylene glycol) -6-cholesteryl-S-triazine compoundInfo
- Publication number
- JPH0696636B2 JPH0696636B2 JP7686388A JP7686388A JPH0696636B2 JP H0696636 B2 JPH0696636 B2 JP H0696636B2 JP 7686388 A JP7686388 A JP 7686388A JP 7686388 A JP7686388 A JP 7686388A JP H0696636 B2 JPH0696636 B2 JP H0696636B2
- Authority
- JP
- Japan
- Prior art keywords
- bis
- cholesteryl
- methoxypolyethylene glycol
- compound
- triazine compound
- 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 - Fee Related
Links
Landscapes
- Steroid Compounds (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Polyethers (AREA)
Description
【発明の詳細な説明】 （発明の分野） 本発明は、2,4−ビス（Ｏ−メトキシポリエチレングリ
コール）６−コレステリル−Ｓ−トリアジン化合物に関
する。FIELD OF THE INVENTION The present invention relates to 2,4-bis (O-methoxy polyethylene glycol) 6-cholesteryl-S-triazine compounds.
（従来の技術） 2,4−ビス（Ｏ−メトキシポリエチレングリコール）−
Ｓ−トリアジン化合物としては、酵素や蛋白質と結合さ
せたものは知られている。たとえばY.Inadaら、Enzyme,
26,49（1981））、 （Y.Inada,FEBS Lett.,178,275（1984）、 Y.Inada,J.Org.Chem.,50,3414（1985）。(Prior Art) 2,4-Bis (O-methoxypolyethylene glycol)-
As the S-triazine compound, those bound with an enzyme or a protein are known. For example, Y. Inada et al., Enzyme,
26, 49 (1981)), (Y.Inada, FEBS Lett., 178, 275 (1984), Y.Inada, J.Org.Chem., 50, 3414 (1985).
しかし、コレステロールを結合させたものに関しては全
く知られていない。However, nothing is known about those bound with cholesterol.
（発明の目的） 本発明の目的は,2,4−ビス（Ｏ−メトキシポリエチレン
グリコール）６−コレステリル−Ｓ−トリアジン化合物
を提供することである。(Object of the Invention) An object of the present invention is to provide a 2,4-bis (O-methoxypolyethylene glycol) 6-cholesteryl-S-triazine compound.
（発明の構成） 本発明の化合物は、式〔１〕で表わされる。(Structure of the Invention) The compound of the present invention is represented by the formula [1].
式中ｎはポリエチレングリコールモノメチルエーテル部
の平均繰り返し数を表し、90以上136以下である。 In the formula, n represents the average number of repeating polyethylene glycol monomethyl ether moieties, and is 90 or more and 136 or less.
本発明の化合物は、以下の２通りの方法で合成すること
ができる。The compound of the present invention can be synthesized by the following two methods.
方法Ａ 方法Ｂ 方法A: コレステロール1.35gとAg2CO30.83gを乾燥エーテル中に
入れ、化合物２PEG2という商品名で生化学工業より市販
されている）500mgを加えて加熱還流10時間を行った。Method A Method B Method A: 1.35 g of cholesterol and 0.83 g of Ag 2 CO 3 were placed in dry ether, and 500 mg of Compound 2 PEG 2 ( commercially available from Seikagaku Kogyo) was added and heated under reflux for 10 hours.
終了後、濾過しエーテルを留去水に溶解しないものを再
濾過後、Sephadex G−100カラムにて分離・精製し凍結
乾燥によって目的の１を得た（480mg）。本品は、クロ
ロホルムに易溶、水、メタノール、エタノールに可溶で
あった。After the completion of the filtration, the product which did not dissolve the ether in the distilled water was filtered again, separated and purified by a Sephadex G-100 column, and freeze-dried to obtain the target 1 (480 mg). This product was readily soluble in chloroform and soluble in water, methanol and ethanol.
m.p.180−192゜ 方法B: 乾燥テトラヒドロフラン100ml中にコレステロール1.35g
を入れた。その中に0.16gの水素化ナトリウム（60％油
中分散物）を入れ40分間室温でかくはんした。その中に
化合物２を500mgをジメチルホルムアミド30mlに溶解さ
せたものを加え、混合物を10時間加熱還流した。mp180-192 ° Method B: 1.35 g cholesterol in 100 ml dry tetrahydrofuran
I put it in. 0.16 g of sodium hydride (60% dispersion in oil) was added thereto, and the mixture was stirred for 40 minutes at room temperature. A solution prepared by dissolving 500 mg of compound 2 in 30 ml of dimethylformamide was added thereto, and the mixture was heated under reflux for 10 hours.
溶媒を減圧留去、水を加え、不溶物を濾過し瀘液を方法
Ａと同じように処理することにより目的のを450mg得
た。The solvent was distilled off under reduced pressure, water was added, the insoluble matter was filtered off, and the filtrate was treated in the same manner as in Method A to obtain 450 mg of the desired product.
化合物１の構造確認は200MHzの1H−NMRを用いて行っ
た。（CD3OD中） 0.8〜2.3（多重線、） 3.4〜3.62（幅広一重線） 全体の分子量に占めるコレステリル基の割合が低いので
面種強度は定かではないが、IR（Nuzol）において活性P
EG2のクロル基に帰因すると考えられる1065cm-1の鋭い
吸収が消失していることを考え合わせるとこの構造は確
かであると判断できる。The structure of Compound 1 was confirmed using 1 H-NMR at 200 MHz. (In CD 3 OD) 0.8-2.3 (multi-line,) 3.4-3.62 (wide singlet) Since the ratio of cholesteryl group to the total molecular weight is low, the face species strength is not clear, but the activity P in IR (Nuzol)
Considering the disappearance of the sharp absorption at 1065 cm -1 , which is thought to be attributed to the chloro group of EG 2 , it can be judged that this structure is certain.
（発明の効果） 本発明の化合物は、脂質を水中に分散させた時に形成さ
れるリポソームの構造を強化するのに有効な化合物であ
る。本発明の化合物とリン脂質を適当な比で混ぜ形成さ
せたリポソームの表面はポリエーテル鎖でおおわれ、生
体内の豊富なNa+、K+を取りこみ表面を強固に保護す
る。またリポーム表面に強い荷電を発生することによ
り、リポソーム自体の凝集も抑制することができる。加
えてエーテル部は他の脂質の親水性部と直接あるいは水
分子を介して水素結合することによりリポソーム内側か
らの内包物のもれを抑制する。(Effect of the Invention) The compound of the present invention is a compound effective for strengthening the structure of liposomes formed when lipids are dispersed in water. The surface of the liposome formed by mixing the compound of the present invention and the phospholipid at an appropriate ratio is covered with a polyether chain, and takes in abundant Na + and K + in the living body to strongly protect the surface. In addition, aggregation of the liposome itself can be suppressed by generating a strong charge on the surface of the liposome. In addition, the ether portion forms a hydrogen bond with the hydrophilic portion of another lipid directly or through a water molecule to suppress leakage of inclusions from the inside of the liposome.
また本化合物の主要部を占るポリエチレングリコール部
は、人工脂質の欠点である主体内毒性という観点でも無
害であることが多くの動物実験で確められしいる。（例
えば、日本癌科学治療雑誌、11巻、2227頁 1984年） 以上の理由により本発明の効果は大きいのである。It has been confirmed by many animal experiments that the polyethylene glycol part, which occupies the main part of the present compound, is harmless from the viewpoint of endotoxicity, which is a drawback of artificial lipids. (For example, Journal of Japanese Cancer Science, Vol. 11, p. 2227, 1984) For the above reasons, the effect of the present invention is great.
Claims (1)
シポリエチレングリコール）−６−コレステリル−Ｓ−
トリアジン化合物。 式１においてｎはポリエチレングリコールモノメチルエ
ーテル部の平均繰り返し数を表し、90以上136以下であ
る。1. A 2,4-bis (O-methoxypolyethylene glycol) -6-cholesteryl-S- represented by the formula 1.
Triazine compounds. In Formula 1, n represents the average number of repeating polyethylene glycol monomethyl ether moieties, and is 90 or more and 136 or less.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7686388A JPH0696636B2 (en) | 1988-03-30 | 1988-03-30 | 2,4-bis (o-methoxypolyethylene glycol) -6-cholesteryl-S-triazine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7686388A JPH0696636B2 (en) | 1988-03-30 | 1988-03-30 | 2,4-bis (o-methoxypolyethylene glycol) -6-cholesteryl-S-triazine compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01249798A JPH01249798A (en) | 1989-10-05 |
| JPH0696636B2 true JPH0696636B2 (en) | 1994-11-30 |
Family
ID=13617489
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7686388A Expired - Fee Related JPH0696636B2 (en) | 1988-03-30 | 1988-03-30 | 2,4-bis (o-methoxypolyethylene glycol) -6-cholesteryl-S-triazine compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0696636B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5159175A (en) * | 1990-10-03 | 1992-10-27 | Terex Corporation | Method of welding a first to a second metal plate |
| US5889153A (en) * | 1994-05-20 | 1999-03-30 | Hisamitsu Pharmaceutical Co., Inc. | Protein or polypeptide, method for producing the same and intermediate compound therefor |
-
1988
- 1988-03-30 JP JP7686388A patent/JPH0696636B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01249798A (en) | 1989-10-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |