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Remedy or diagnostic for inflammatory disease containing target-directing liposome

An inflammatory disease, liposome technology, applied in the field of drug delivery systems for inflammatory diseases, can solve problems such as unclear pathogenesis

Inactive Publication Date: 2006-11-15
NAT INST OF ADVANCED IND SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Some people think that the pathogenesis of RA is related to genetic factors (specific HLA, etc.) or environmental factors (virus infection, etc.), but the detailed pathogenesis is still unclear

Method used

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  • Remedy or diagnostic for inflammatory disease containing target-directing liposome
  • Remedy or diagnostic for inflammatory disease containing target-directing liposome
  • Remedy or diagnostic for inflammatory disease containing target-directing liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0183] The preparation of embodiment 1 liposome

[0184] Liposomes were prepared using a modified cholic acid dialysis method according to a reported method (Yamazaki, N., Kodama, M. and Gabius, H.-J. (1994) Methods Enzymol. 242, 56-65). That is, dipalmitoylphosphatidylcholine, cholesterol, dihexadecyl phosphate, ganglioside and diacetate with a molar ratio of 35:40:5:15:5 and a total lipid content of 45.6 mg Add 46.9mg of sodium cholate to palmitoylphosphatidylethanolamine and dissolve in 3ml of chloroform / methanol solution. The solution was evaporated and the precipitate was dried in vacuo to obtain a lipid film. The obtained lipid film was suspended in 3 ml of TAPS buffer (pH 8.4), and subjected to ultrasonic treatment to obtain a transparent micellar suspension. The micellar suspension was subjected to ultrafiltration using PM10 membrane (Amicon Co., USA) and PBS buffer (pH 7.2) to prepare 10 ml of uniform liposomes (average particle size 100 nm).

Embodiment 2

[0185] The hydrophilicity treatment on embodiment 2 liposome lipid membrane face

[0186] Using XM300 membrane (AmiconCo., USA) and CBS buffer (pH8.5), 10 ml of the liposome solution prepared in Example 1 was subjected to ultrafiltration so that the pH of the solution was 8.5. Next, 10 ml of cross-linking reagent bis(sulfosuccinimidyl) suberate (BS3; Pierce Co., USA) was added and stirred at 25° C. for 2 hours. Then, stir overnight at 7° C. to terminate the chemical bonding reaction between lipid dipalmitoylphosphatidylethanolamine and BS3 on the liposome membrane. The liposome fluid was ultrafiltered with XM300 membrane and CBS buffer (pH 8.5). Next, 40 mg of tris(hydroxymethyl)aminomethane dissolved in 1 ml of CBS buffer (pH8.5) was added to 10 ml of liposome liquid, stirred at 25° C. for 2 hours, and then stirred overnight at 7° C. The chemical bonding reaction of lipid-bound BS3 and tris(hydroxymethyl)aminomethane on the liposome membrane is terminated. As a result, the...

Embodiment 3

[0187] The combination of embodiment 3 human serum albumin (HSA) and liposome membrane face

[0188] The coupling reaction was carried out according to the reported method (Yamazaki, N., Kodama, M. and Gabius, H.-J. (1994) Methods Enzymol. 242, 56-65). That is, this reaction is carried out with 2 step chemical reactions, at first, the sodium metaperiodate that 43mg is dissolved in the 1ml TAPS damping fluid (pH8.4) is added in the 10ml liposome that embodiment 2 obtains, stir at room temperature For 2 hours, gangliosides present on the membrane surface were subjected to periodic acid oxidation, and then ultrafiltered through an XM300 membrane and PBS buffer (pH 8.0) to obtain 10 ml of oxidized liposomes. Add 20 mg of human serum albumin (HSA) to the liposome liquid, stir at 25°C for 2 hours, then add 100 μl of 2M NaBH to PBS (pH 8.0) 3 CN, stirred overnight at 10°C, binds HSA through the coupling reaction of gangliosides on liposomes to HSA. Ultrafiltration was carried out w...

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Abstract

There is provided targeting drug delivery system (DDS) nanoparticles that can be accumulated in target tissues such as inflammatory sites of inflammatory diseases and can thus be utilized in a therapeutic or diagnostic DDS for locally delivering drugs or genes to the affected parts. The present invention provides a pharmaceutical composition for the medical treatment or diagnosis of an inflammatory disease comprising a sugar-modified liposome having a sugar chain bound to the membrane of the liposome.

Description

technical field [0001] The present invention relates to drug delivery systems for inflammatory diseases. Background technique [0002] One of the specific goals pursued in the National Nanotechnology Strategy (NNI) of the United States is "drug or gene delivery system (DDS: drug delivery system) that attacks cancer cells or target tissues". In the nanotechnology and materials field promotion strategy of Japan's General Science and Technology Committee, the key areas are "medical ultramicrosystems and materials, and nanobiology controlled by the mechanism of utilization and control of biology". One of its research and development goals within 5 years is "Establishment of the basis for technologies such as functional materials for the body and targeted therapy for extending healthy lifespan". On the other hand, with the aging society, the morbidity and mortality of cancer are increasing year by year, and it is expected to develop a new type of therapeutic material - targeted ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/24A61K47/26A61K47/28A61K47/36A61K47/54A61K47/69A61K49/00A61P29/00
Inventor 山崎登鹤岛英夫大黑伸行
Owner NAT INST OF ADVANCED IND SCI & TECH
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