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Vesicle preparation

A technology of vesicles and substances, which is applied in the directions of antiviral agents, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., can solve the problems of undeveloped hepatic parenchymal cell delivery particles, etc.

Active Publication Date: 2011-12-21
CHUGAI PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, no delivery particle optimal for delivery to hepatic parenchymal cells has been developed

Method used

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Examples

Experimental program
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Effect test

Embodiment 1

[0146] N-(α-trimethylammonium acetyl)-dioleyl-D-glutamic acid chloride (Mutual Pharmaceutical Co., Ltd., Japan; trade name: DC-3-18:1), dioleoylphosphatidyl Ethanolamine (NOF Corporation, Japan) and cholesterol (Wako Pure Chemical Industries, Ltd., Japan) were dissolved in an appropriate amount of chloroform at a mixing ratio of 40:30:30 (molar ratio), and the solvent was distilled off under reduced pressure. Dried to make a lipid mixture.

[0147] Dry with a desiccator until the solvent can be reliably removed, then add 9% sucrose solution to the lipid mixture, and indirectly irradiate with ultrasonic waves using an ultrasonic generator under heating at 65°C, thereby obtaining a total lipid concentration of 2.5mM liposome coarse dispersion. Next, in order to make the liposome particle size uniform, two filters with a pore size of 0.2 μm were stacked and loaded into an extruder, and extruded under heat and pressure at about 65° C. (extrusion filtration). Furthermore, the same ...

Embodiment 2

[0151] DL-α-tocopherol was dissolved in a ratio of 2.5 μmol to DL-α-tocopherol (Tokyo Chemical Co., Ltd., Japan) and 400 μL of ethanol, and a filtrate (tocopherol liquid) filtered through a 0.2 μm filter was prepared.

[0152] In a 50 mL vial, 10 mL of the liposome dispersion prepared in [Example 1] was added, and 400 μL of tocopherol solution (10.0% relative to the total number of lipid moles) was added, followed by vortex mixing for 20 seconds. Further, incubation was carried out at room temperature for 1 hour to obtain a liposome dispersion in which vitamin E was adsorbed. The average particle diameter is 136.7 nm.

Embodiment 3

[0154] DL-α-tocopherol was dissolved in a ratio of 3.75 μmol to DL-α-tocopherol (Tokyo Chemical Co., Ltd., Japan) and 400 μL of ethanol, and a filtrate (tocopherol liquid) filtered through a 0.2 μm filter was prepared.

[0155] Into a 50 mL vial, 10 mL of the liposome dispersion prepared in [Example 1] was added, and 400 μL of the tocopherol solution (15.0% relative to the total number of lipid moles) was added, followed by vortex mixing for 20 seconds. Further, incubation was carried out for 1 hour at room temperature to obtain a liposome dispersion in which vitamin E was adsorbed. The average particle diameter is 133.5 nm.

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Abstract

It is found that a biologically active substance contained in an endoplasmic reticulum can be delivered to a hepatocyte efficiently and specifically by adsorbing or chemically binding vitamin E to the surface of the endoplasmic reticulum.  This can be achieved by utilizing a serum component's property to deliver vitamin E to a hepatocyte.

Description

technical field [0001] The invention relates to a vesicle (small cell body, vesicle) capable of effectively introducing physiologically active substances into hepatic parenchymal cells and making the physiologically active substances effectively act in the hepatic parenchymal cells and its application. Background technique [0002] The present invention relates to antiviral agents, chemotherapeutic agents, peptides, nucleotides, oligonucleotides, antisense nucleic acids, aptamers, decoys and their analogs, small nucleic acid molecules such as siRNA, miRNA, dsRNA or shRNA, etc. Physiologically active substances are effectively introduced into the hepatic parenchymal cells, and the vesicles that allow the physiologically active substances to effectively act in the hepatic parenchymal cells. [0003] Examples are known in which nucleic acids such as genes or physiologically active substances such as antitumor agents are introduced into hepatic parenchymal cells to achieve gene ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/136A61K31/17A61K31/198A61K31/255A61K31/282A61K31/337A61K31/395A61K31/407A61K31/4164A61K31/4745A61K31/475A61K31/505A61K31/506A61K31/675A61K31/7008A61K31/704A61K31/7048A61K31/7088A61K33/24A61K38/00A61K38/21A61K45/00A61K47/18A61K47/22A61P3/00A61P31/12A61P35/00
CPCA61K47/18A61K31/136A61K31/475A61K31/505A61K31/704A61K31/17A61K31/337A61K31/7088A61K31/255A61K38/00A61K9/127A61K31/506A61K31/7008A61K31/395A61K31/675A61K31/407A61K31/7048A61K31/4164A61K47/22A61K31/282A61K31/198A61K47/48815A61K47/6911A61P3/00A61P31/12A61P35/00
Inventor 小原道法中野善郎蜂须丽水谷幸雄须藤正幸
Owner CHUGAI PHARMA CO LTD
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