JPH0553537B2 - - Google Patents
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- Publication number
- JPH0553537B2 JPH0553537B2 JP62042827A JP4282787A JPH0553537B2 JP H0553537 B2 JPH0553537 B2 JP H0553537B2 JP 62042827 A JP62042827 A JP 62042827A JP 4282787 A JP4282787 A JP 4282787A JP H0553537 B2 JPH0553537 B2 JP H0553537B2
- Authority
- JP
- Japan
- Prior art keywords
- suspension
- liposomes
- aqueous solution
- liposome
- hemoglobin
- 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
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/795—Porphyrin- or corrin-ring-containing peptides
- C07K14/805—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1277—Preparation processes; Proliposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は新規なリポソームの製法に関するもの
である。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel method for producing liposomes.
さらに詳しくは、本発明は高粘度の水溶液を内
部に取り込んでなるリポソームの製法に関する。
リポソーム（liposome）は脂質２分子膜からな
り、内部に水層を含んだ閉鎖小胞対である。生体
膜は脂質の２分子構造をとつているといわれてお
り、従つてリポソームの生体膜のモデル膜として
その物理化学的性質の研究に広く用いられてい
る。また、リポソームは内部の水層や膜内に種々
の物質を取り込むことができ、細胞と融合した
り、細胞に取り込まれたりするので生体内へ物質
を送り込むキヤリヤーとして利用される。リポソ
ームを利用した研究は生物学、医学、薬学など広
範な分野にわたつており、酵素や制ガン剤を運ぶ
キヤリヤーとしての利用、免疫学分野での利用、
細胞との相互作用、ドラツクデリバリーシステム
としての利用等が研究されている。 More specifically, the present invention relates to a method for producing liposomes containing a highly viscous aqueous solution.
Liposomes are closed vesicle pairs consisting of a lipid bilayer membrane and containing an internal water layer. Biological membranes are said to have a bimolecular structure of lipids, and are therefore widely used as model membranes for liposome biological membranes in studies of their physicochemical properties. In addition, liposomes can incorporate various substances into their internal aqueous layers and membranes, and are used as carriers to transport substances into living organisms because they fuse with or are taken up by cells. Research using liposomes spans a wide range of fields, including biology, medicine, and pharmacy, including use as carriers for enzymes and anticancer drugs, use in the field of immunology,
Research is being carried out on its interaction with cells and its use as a drug delivery system.
［従来の技術］
リポソームは上述したように極めて広範な利用
分野を有するが、従来のリポソームの製法では、
高粘度の水溶液を内部に取り込んだリポソームを
得ることは不可能であつた。従来のリポソームの
製法としてはいわゆる薄膜法、界面活性剤除去法
および逆相法等が知られている。薄膜法の容器の
内面にリポソーム形成脂質の薄膜をつくり、そこ
へ取り込ませたい物質を溶解させた水溶液を加
え、振盪処理するかまたは超音波処理してリポソ
ームをつくる方法である。界面活性剤除去法は取
り込ませたい物質を溶解させた水溶液にリポソー
ム形成吸脂質と界面活性剤を溶解させて混合ミセ
ルをつくり、次いで透析により界面活性剤を除去
しリポソームをつくる方法がある。逆相法は、リ
ポソーム形成脂質を溶かした有機溶媒溶液に取り
込ませたい物質を溶解させた水溶液を加えてＷ／
Ｏ型エマルジヨンを作成し、次いで有機溶媒をエ
バポレーシヨンで除去してリポソームをつくる方
法である。これらの従来法によれば、内部に取り
込ませる水溶液が低粘度である場合にはリポソー
ムが生成する10cP（４℃）以上の高粘度になると
極端に収率が悪くなるとともに所望のリポソーム
が得られないことがあり、リポソーム利用上大き
な制約となつていた。例えば、人工赤血球として
ヘモグロビン水溶液を含有するリポソームが知ら
れているが粘度の制約のため、ヘモグロビン濃度
を天然のそれであるが35％（ｗ／ｖ）にまで高め
ることができず、せいぜい15％程度であり、酸素
運搬能の低いものしか得られていない。[Prior Art] As mentioned above, liposomes have an extremely wide range of applications, but conventional liposome manufacturing methods
It has been impossible to obtain liposomes incorporating a highly viscous aqueous solution. Conventional methods for producing liposomes include the so-called thin film method, surfactant removal method, and reverse phase method. The thin film method is a method in which a thin film of liposome-forming lipid is created on the inner surface of a container, an aqueous solution containing a substance to be incorporated is added thereto, and the mixture is shaken or treated with ultrasound to form liposomes. A surfactant removal method involves dissolving a liposome-forming lipid and a surfactant in an aqueous solution containing a substance to be incorporated to create a mixed micelle, and then removing the surfactant by dialysis to create liposomes. In the reverse phase method, an aqueous solution containing a substance to be incorporated is added to an organic solvent solution containing a liposome-forming lipid dissolved in W/
This is a method of creating liposomes by creating an O-type emulsion and then removing the organic solvent by evaporation. According to these conventional methods, if the aqueous solution taken into the interior has a low viscosity, liposomes will be formed.If the viscosity becomes higher than 10cP (4℃), the yield will be extremely poor and the desired liposomes will not be obtained. This has been a major constraint on the use of liposomes. For example, liposomes containing an aqueous hemoglobin solution are known as artificial red blood cells, but due to viscosity restrictions, it is not possible to increase the hemoglobin concentration to 35% (w/v) of natural hemoglobin, and it is only about 15% at most. Therefore, only those with low oxygen carrying capacity have been obtained.
［発明が解決しようとする問題点］
従つて本発明の目的は内部に高粘度の水溶液を
取り込んでなるリポソームぼ製造方法を提供する
ことにある。[Problems to be Solved by the Invention] Accordingly, an object of the present invention is to provide a method for producing liposomes in which a highly viscous aqueous solution is incorporated.
［問題点を解決するための手段］
本発明は上記目的を達成するために下記の構成
を有する。[Means for Solving the Problems] The present invention has the following configuration to achieve the above object.
(1) リポソーム膜形成脂質を有機溶媒に溶解し、
該溶液から溶媒留去し、残留物に水溶液を加
え、振盪処理または超音波処理することにより
均一な懸濁液とし、該懸濁液を不活性ガスで80
〜130Kg／cm2に加圧し、不活性ガスを該懸濁液
に十分浸透させた後、該懸濁液を細〓から高圧
吐出処理することを特徴とするリポソームの製
法。(1) Dissolve the liposome membrane-forming lipid in an organic solvent,
The solvent is distilled off from the solution, an aqueous solution is added to the residue, and a homogeneous suspension is obtained by shaking or ultrasonication.
A method for producing liposomes, which comprises pressurizing the suspension to ~130 Kg/cm 2 and sufficiently permeating the suspension with an inert gas, and then subjecting the suspension to high-pressure discharge treatment through a narrow tube.
(2) 水溶液の粘度が10〜3000cP（４℃）である第
１項記載のリポソームの製法。(2) The method for producing liposomes according to item 1, wherein the aqueous solution has a viscosity of 10 to 3000 cP (4°C).
(3) ガス加圧式高圧吐出乳化機を使用して懸濁液
を高圧吐出処理する第１項記載のリポソームの
製法。(3) The method for producing liposomes according to item 1, wherein the suspension is subjected to high-pressure discharge treatment using a gas pressurized high-pressure discharge emulsifier.
本発明におけるリポソーム膜形成脂質には特に
制限はなく、リポソームを形成するものであれば
天然または合成の脂質が使用可能である。特にリ
ン脂質が好適に使用され、その例として、レシチ
ン、ホスフアチジルエタノールアミン、ホスフア
チジン酸、ホスフアチジルセリン、ホスフアチジ
ルイノシトール、ホスフアチジルグリセロール、
スフインゴミエリン、カルジオリピンおよびこれ
らを常法に従つて水素添加したものがあげられ、
これらを組合せて用いることもできる。さらにリ
ポソーム膜の構成成分には所望によりステロール
等の膜構造強化剤や電荷付与物質（例えばステア
リン酸、オレイン酸、リノール酸、リノレン酸、
ホスフアチジン酸、ホスフアチジルグリセロール
等）の崩壊時間調節剤を添加することができる。
リポソームの内部に取り込まれる高粘度水溶液に
は特に制限はなく、任意の種類の化学物質の水溶
液が使用されうる。化学物質の例としては、前述
したヘモグロビンの他、β−グルクロニダーゼ、
ヘパリナーゼ、α−グルコシダーゼ等の高分子化
合物があげられる。 The liposome membrane-forming lipid in the present invention is not particularly limited, and any natural or synthetic lipid can be used as long as it forms liposomes. In particular, phospholipids are preferably used, examples of which include lecithin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol,
Examples include sphingomyelin, cardiolipin, and hydrogenated products of these according to conventional methods.
These can also be used in combination. Furthermore, the constituent components of the liposome membrane may include membrane structure reinforcing agents such as sterols and charge-imparting substances (e.g. stearic acid, oleic acid, linoleic acid, linolenic acid,
A disintegration time regulator (such as phosphatidic acid, phosphatidylglycerol, etc.) can be added.
There is no particular restriction on the high viscosity aqueous solution incorporated into the interior of the liposome, and any type of aqueous solution of a chemical substance can be used. Examples of chemical substances include, in addition to the aforementioned hemoglobin, β-glucuronidase,
Examples include high molecular compounds such as heparinase and α-glucosidase.
水溶液の粘度は、リポソームの用途に応じて溶
質の種類および粘度が決定され、それに従つて決
定される。本発明においては10cP〜3000cP（４
℃）の範囲の粘度を有する水溶液が使用される。
10cP（４℃）以下の粘度の水溶液も本発明の方法
において使用可能であるが、これらは従来の製法
においても使用することができる。人工赤血球を
作製する場合には、ヘモグロビン濃度30〜60％
（ｗ／ｖ）の水溶液を使用するのが好ましく、こ
の場合の粘度は10〜3000cP（４℃）である。 The viscosity of the aqueous solution is determined depending on the type and viscosity of the solute depending on the use of the liposome. In the present invention, 10cP to 3000cP (4
An aqueous solution with a viscosity in the range (°C) is used.
Aqueous solutions with viscosities below 10 cP (4° C.) can also be used in the process of the invention, but they can also be used in conventional manufacturing methods. When producing artificial red blood cells, the hemoglobin concentration is 30-60%.
(w/v) aqueous solutions with a viscosity of 10 to 3000 cP (at 4° C.) are preferably used.
本発明のリポソームは、リポソーム膜形成脂質
を有機溶媒に溶解し、該溶媒から溶媒を留去し、
残留物に高粘度の水溶液を加え、振盪処理するか
または超音波処理することにより均一な懸濁液と
し、該懸濁液を不活性ガスで加圧し、不活性ガス
を該懸濁液に十分浸透させた後、該懸濁流を細〓
から高圧吐出処理することによつて製造される。 The liposome of the present invention can be obtained by dissolving liposome membrane-forming lipids in an organic solvent, distilling off the solvent from the solvent,
A highly viscous aqueous solution is added to the residue, shaken or sonicated to form a homogeneous suspension, the suspension is pressurized with an inert gas, and the inert gas is sufficiently applied to the suspension. After infiltration, the suspension stream is
It is manufactured by high-pressure discharge treatment.
上記方法において、均一な懸濁液を調整するま
での工程は前述した薄膜法として知られるリポソ
ームの製造法と同じであり、それ自体公知の方法
に従つて実施される。有機溶媒はリポソームの用
途によつて適宜選択されるが、通常クロロホル
ム、ジクロロメタン等が用いられる。 In the above method, the steps up to preparing a uniform suspension are the same as the liposome manufacturing method known as the thin film method described above, and are carried out in accordance with a method known per se. The organic solvent is appropriately selected depending on the use of the liposome, but chloroform, dichloromethane, etc. are usually used.
かくして得られた懸濁液は細〓ノズル付きの加
圧容器内で不活性ガス（例えば窒素もしくはアル
ゴンガス）で加圧される。加圧は80〜130Kg／cm2
が適当である。不活性ガスが懸濁液に十分浸透し
たのち、懸濁液をノズルから吐出処理する。 The suspension thus obtained is pressurized with an inert gas (for example nitrogen or argon gas) in a pressurized vessel equipped with a narrow nozzle. Pressure is 80-130Kg/cm 2
is appropriate. After the inert gas has sufficiently penetrated into the suspension, the suspension is discharged from the nozzle.
その際懸濁液中の粒子が機器壁に高エネルギー
で衝突するとともに懸濁液中のガスが急激に膨張
する。この衝突およびガス膨張によりリポソーム
が形成されると考えられ、高圧で吐出されるほど
リポソームの粒径は小さくなる。かくして得られ
るリポソーム液息は常法に従つて洗浄され、超遠
心処理等によつて採取される。 At this time, the particles in the suspension collide with the equipment wall with high energy, and the gas in the suspension rapidly expands. It is thought that liposomes are formed by this collision and gas expansion, and the particle size of liposomes becomes smaller as the pressure is discharged. The liposome liquid thus obtained is washed according to a conventional method and collected by ultracentrifugation or the like.
次に実施例を示して本発明をさらに具体的に説
明する。 Next, the present invention will be explained in more detail with reference to Examples.
実施例
(1) 赤血球膜除去ヘモグロビンの調整
常法に従つて調整した赤血球除去ヘモグロビ
ン（SFH）水溶液（ヘモグロビン濃度８％
（ｗ／ｖ）12を透析用ダイアライザー
TAF10W（テルモ社製のセルロース系中空系ダ
イアライザー）を用いて限界過により濃縮
し、ヘモグロビン濃度50％（ｗ／ｖ）のSFH
水溶液1.8を得る。Example (1) Preparation of red blood cell membrane-depleted hemoglobin A red blood cell membrane-depleted hemoglobin (SFH) aqueous solution (hemoglobin concentration 8%) prepared according to a conventional method.
(w/v) 12 dialyzer for dialysis
SFH with a hemoglobin concentration of 50% (w/v) was concentrated using TAF10W (cellulose-based hollow dialyzer manufactured by Terumo Corporation) by limit excess.
Obtain an aqueous solution of 1.8.
(2) リポソーム形成脂質の調整
水素添加率80％の精製ホスフアチジルコリン
27.76ｇ、コレステロール6.96ｇ、水素添加率
80％の精製ホスフアチジン酸3.75ｇをクロロホ
ルム溶解する。該脂質溶液をナスフラスコに入
れ、エバポレーシヨンを行ないクロロホルムを
除去し、ナスフラスコの底に脂質膜を形成させ
る。さらに真空乾燥を16時間行ないクロロホル
ムを完全に除去する。(2) Adjustment of liposome-forming lipids Purified phosphatidylcholine with hydrogenation rate of 80%
27.76g, cholesterol 6.96g, hydrogenation rate
Dissolve 3.75 g of 80% purified phosphatidic acid in chloroform. The lipid solution is placed in an eggplant flask, and evaporation is performed to remove chloroform and form a lipid film on the bottom of the eggplant flask. Further, vacuum drying is performed for 16 hours to completely remove chloroform.
(3) SFH・脂質の懸濁液作成
前記SFH調整工程で得られた50％SFHのう
ち、300mlを該脂質膜に添加して、振盪または
超音波により均一な懸濁液とし、これを原料溶
液とする。(3) Preparation of SFH/lipid suspension Add 300ml of the 50% SFH obtained in the SFH adjustment step to the lipid membrane, make a homogeneous suspension by shaking or ultrasound, and use this as the raw material. Make a solution.
(4) 不活ガスを用いた加圧吐出によるヘモグロビ
ン含有リポソームの作成
該原料溶液を細〓ノズル付きの加圧容器（図
１）に入れチツ素ガスを導入し130Kg／cm2に加
圧する。30分間放置し、チツ素ガスを十分に原
料溶液に浸透させる。次にノズルのバルブを
徐々に開放し、130Kg／cm2の圧力を維持しなが
ら原料溶液を吐出させる。(4) Preparation of hemoglobin-containing liposomes by pressurized discharge using inert gas The raw material solution is placed in a pressurized container with a narrow nozzle (Fig. 1), nitrogen gas is introduced, and the pressure is increased to 130 Kg/cm 2 . Leave it for 30 minutes to allow the nitrogen gas to fully penetrate into the raw material solution. Next, the nozzle valve is gradually opened and the raw material solution is discharged while maintaining a pressure of 130 kg/cm 2 .
(5) ヘモグロビン含有リポソームの精製
加圧吐出後の液を生理食塩水で10倍に希釈し
遠心（17000rpm、30min）により、ヘモグロ
ビン含有リポソームの沈殿として分離する。上
澄のカプセル化に関与しなかつたヘモグロビン
溶液をデカンテーシヨンで除き、その後生理食
塩水でヘモグロビン含有リポソーム沈殿を懸濁
させ、再度遠心を行なう。以下同様の操作を上
澄にヘモグロビンが検出されなくなるまで繰り
返す。(5) Purification of hemoglobin-containing liposomes After pressurized discharge, dilute the liquid 10 times with physiological saline and centrifuge (17,000 rpm, 30 min) to separate hemoglobin-containing liposomes as precipitates. The hemoglobin solution that did not participate in the encapsulation of the supernatant was removed by decantation, and then the hemoglobin-containing liposome precipitate was suspended in physiological saline and centrifuged again. Similar operations are repeated until no hemoglobin is detected in the supernatant.
(6) 粗大粒子の除去
精製後のヘモグロビン含有リポソームの懸濁
液を0.4μのニユークリポアメンブレン（材質：
ポリカーボネイト）にて過して粗大粒子を取
り除く。(6) Removal of coarse particles The purified suspension of hemoglobin-containing liposomes was transferred to a 0.4μ nuclepore membrane (material:
(polycarbonate) to remove coarse particles.
(7) ヘモグロビン濃度調整
最終的にリポソームを生理食塩水に懸濁し、
ヘモグロビン濃度10％に調整したリポソーム懸
出液が180ml得られた。(7) Adjustment of hemoglobin concentration Finally, the liposomes are suspended in physiological saline,
180 ml of liposome suspension with hemoglobin concentration adjusted to 10% was obtained.
［発明の効果］
本発明によれば、内部に高粘度の水溶液を取り
込んだリポソームの製法が提供される。従つて高
分子化合物を高濃度に溶解した水溶液を含有する
リポソームを作製することができ、リポソームの
より広範な利用が可能となる。例えばヘモグロビ
ン濃度30〜60％（ｗ／ｖ）の水溶液（10〜
3000cP（４℃））を含有するリポソームを調整す
ることができ、このものは従来の人工赤血球に比
較してヘモグロビンの濃度が高いので酵素運搬能
が優れている。[Effects of the Invention] According to the present invention, a method for producing liposomes incorporating a highly viscous aqueous solution therein is provided. Therefore, liposomes containing an aqueous solution in which a polymer compound is dissolved at a high concentration can be produced, and the liposomes can be used more widely. For example, an aqueous solution with a hemoglobin concentration of 30-60% (w/v) (10-60% (w/v)
It is possible to prepare liposomes containing 3,000 cP (at 4°C)), which have a higher concentration of hemoglobin than conventional artificial red blood cells and therefore have superior enzyme-carrying ability.
さらに本発明の製法においては、リポソーム膜
形成脂質の懸濁液から細〓から高圧吐出される際
に、懸濁液中の不活性ガスが圧力膨張するので従
来の高圧吐出法に比較してリポソームが効率よく
形成される。その結果、吐出処理の回数が少なく
てすみ、ヘモグロビンのような酸化に不安定な物
質のリポソーム化に好適に使用される。 Furthermore, in the production method of the present invention, when a suspension of liposome membrane-forming lipids is discharged from a thin tube at high pressure, the inert gas in the suspension expands under pressure, so that liposomes are is formed efficiently. As a result, the number of discharge processes is reduced, and it is suitably used to form liposomes of substances unstable to oxidation, such as hemoglobin.
Claims (1)
該溶液から溶媒を留去し、残留物に水溶液を加
え、振盪処理または超音波処理することにより均
一な懸濁液とし、該懸濁液を不活性ガスで80〜
130Kg／cm2に加圧し、不活性ガスを該懸濁液に十
分浸透させた後、該懸濁液を細〓から高圧吐出処
理することを特徴とするリポソームの製法。 ２ 水溶液の粘度が10〜3000cP（４℃）である特
許請求の範囲第１項記載のリポソームの製法。 ３ ガス加圧式高圧吐出型乳化機を使用して懸濁
液を高圧吐出処理する特許請求の範囲第１項記載
のリポソームの製法。[Claims] 1. Liposome membrane-forming lipids are dissolved in an organic solvent,
The solvent is distilled off from the solution, an aqueous solution is added to the residue, and a homogeneous suspension is obtained by shaking or ultrasonication.
A method for producing liposomes, which comprises pressurizing the suspension to 130 Kg/cm 2 and sufficiently permeating the suspension with an inert gas, and then subjecting the suspension to high-pressure discharge treatment through a fine tube. 2. The method for producing liposomes according to claim 1, wherein the aqueous solution has a viscosity of 10 to 3000 cP (4°C). 3. The method for producing liposomes according to claim 1, wherein the suspension is subjected to high-pressure discharge treatment using a gas pressurized high-pressure discharge emulsifier.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62042827A JPS63209746A (en) | 1987-02-27 | 1987-02-27 | Liposome manufacturing method |
| DE8888902213T DE3872875T2 (en) | 1987-02-27 | 1988-02-26 | METHOD FOR PRODUCING LIPOSOME. |
| AU13648/88A AU608304B2 (en) | 1987-02-27 | 1988-02-26 | Process for preparing liposome |
| US07/408,485 US5049391A (en) | 1987-02-27 | 1988-02-26 | Liposome encapsulated hemoglobin |
| PCT/JP1988/000208 WO1988006437A1 (en) | 1987-02-27 | 1988-02-26 | Process for preparing liposome |
| EP88902213A EP0357773B1 (en) | 1987-02-27 | 1988-02-26 | Process for preparing liposomes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62042827A JPS63209746A (en) | 1987-02-27 | 1987-02-27 | Liposome manufacturing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63209746A JPS63209746A (en) | 1988-08-31 |
| JPH0553537B2 true JPH0553537B2 (en) | 1993-08-10 |
Family
ID=12646793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62042827A Granted JPS63209746A (en) | 1987-02-27 | 1987-02-27 | Liposome manufacturing method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63209746A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9235075B2 (en) | 2012-05-22 | 2016-01-12 | Kent Displays Incorporated | Electronic display with patterned layer |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4617458B2 (en) * | 2004-02-10 | 2011-01-26 | 財団法人ヒューマンサイエンス振興財団 | Method for producing liposome using hollow fiber dialysis column |
| WO2012137834A1 (en) * | 2011-04-04 | 2012-10-11 | 学校法人早稲田大学 | Method for producing endoplasmic reticulum |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2534487B1 (en) * | 1982-10-15 | 1988-06-10 | Dior Christian Parfums | METHOD FOR THE HOMOGENEIZATION OF HYDRATED LIPIDAL LAMELLAR PHASE DISPERSIONS, AND SUSPENSIONS OBTAINED THEREBY |
-
1987
- 1987-02-27 JP JP62042827A patent/JPS63209746A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9235075B2 (en) | 2012-05-22 | 2016-01-12 | Kent Displays Incorporated | Electronic display with patterned layer |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63209746A (en) | 1988-08-31 |
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| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |