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WO2000061114A1 - Particules fines ciblant des cellules, et procede de production correspondant - Google Patents

Particules fines ciblant des cellules, et procede de production correspondant Download PDF

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Publication number
WO2000061114A1
WO2000061114A1 PCT/JP2000/002272 JP0002272W WO0061114A1 WO 2000061114 A1 WO2000061114 A1 WO 2000061114A1 JP 0002272 W JP0002272 W JP 0002272W WO 0061114 A1 WO0061114 A1 WO 0061114A1
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Prior art keywords
fine particles
cell
ligand
cells
water
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PCT/JP2000/002272
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English (en)
Japanese (ja)
Inventor
Toshiaki Tagawa
Hisae Niki
Tomoko Saisho
Kazuo Maruyama
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Mitsubishi Chemical Corporation
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Publication date
Application filed by Mitsubishi Chemical Corporation filed Critical Mitsubishi Chemical Corporation
Priority to AU36735/00A priority Critical patent/AU3673500A/en
Publication of WO2000061114A1 publication Critical patent/WO2000061114A1/fr

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Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
    • A61K47/6907—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a microemulsion, nanoemulsion or micelle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
    • A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
    • A61K47/6913—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome the liposome being modified on its surface by an antibody
    • 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
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention provides a microparticle having a function by combining ligands such as proteins, peptides, carbohydrates, hormones, and low molecular compounds. It relates to the particles and their manufacturing method.
  • the microparticles obtained by the present invention can be used for drug carriers, diagnostics, inspections, etc. c.
  • Lipids having a polar group or amphiphilic polymers, etc. can be formed by vesicles such as lipidic micelles, macromolecular micelles, ribosomes, etc. Used together with the component, it forms microparticles such as microemulsion. This is these key to that trial only for profit as the Ya Li Aichi such as fine-grain child the medicine agents and nuclear acid been Do rather than multi recent years Les, Ru c
  • a fat-soluble substance in the case of ribosome, can be sealed in the fat phase, and a water-soluble substance can be sealed in the internal aqueous phase.
  • DDS carriers such as proteins and nucleic acids.
  • liposomes in which ligands such as antibodies and sugar chains have been studied have been studied.
  • liposomes in which an antibody against a carcinoembryonic antigen has been conjugated can be mentioned.
  • ribosome By applying force to the cell surface, it is spread inside the cell.
  • the purpose of delivering the ribosome is to combine the interlocking leg with the ribosome or to be internalized.
  • Antibodies against identified antigens have been used, and ribosomes have been used-for example, targeting cancer cells.
  • anti-Her 2 antibody-binding ribosome (Cancer Lett. 118 (2) (1997) 153), anti-transferrin receptor Liposome conjugated with antibody (Br_J-Cancer.
  • trans-ferrin or an antibody against trans-ferrin is used, inter-cellularization of cells is expected.
  • trans-ferrin is highly expressed in only a limited number of cancer cells, and is also slightly expressed in many normal cells. In fact, the targets that could actually be applied were limited. Disclosure of the invention
  • the present inventors have conducted research, and have found that, as a result of the research, target cells are bound to target cells on microparticles. Incorporation into the target cells of the cauldron The fine particles are transported into the cells by adding active ligands. Look at it.
  • the gist of the present invention is that the specific particles are targeted to the specific particles, and the fine particles are capable of binding to the specific cells.
  • a ligand capable of binding to the cell binds to the microparticles via a water-soluble polymer.
  • these are fine particles, and are particularly preferred.
  • the ligands that bind to the cells are separated by water-soluble polymers.
  • the fine particles are bonded to the fine particles by the method described above, and further, the water-soluble polymer is bonded to the fine particles.
  • another gist of the present invention is that a ligand capable of binding to a target cell is bound via a water-soluble polymer to form a target cell. And a specific cell that binds a ligand having a function to be taken into the cell and a water-soluble polymer.
  • This is a method for producing fine particles to be bound, and it is a method of combining a ligand and a water-soluble polymer that are capable of binding to target cells in advance.
  • the conjugate is manufactured, and the conjugate, a ligand capable of being incorporated into cells, and a water-soluble polymer are combined into fine particles. It is in the method of producing fine particles that is characterized in that they are combined.
  • Fig. 1 shows that the ligand (A) that binds to the cell is bound to the ribosome via the water-soluble polymer, and is taken into the cell.
  • Fig. 2 shows the liposomes in human gastric cancer cell line VIKN45 cells, and the fluorescence images of the ribosomes labeled with fluorescent light. It is true. After reacting each liposome to MKN 45 cells under ice-cooling for 1 hour, washing, and comparing the responsiveness at the point where the cells were further reacted for 371 hours, compare them.
  • a is the fluorescence image after reacting the 2 1 B 2 ribosome
  • b is the 2 1 B 2 -TF liposome
  • c is the TF liposome after the reaction. Indicates.
  • Fig. 3 shows the reactivity of each liposome to human gastric cancer cell line MKN45 cells and the internalization characteristics of each ribosome by fluorescence observation. This is the result (photograph) of the comparison.
  • a and b are 2 1 B 2 ribosomes (without washing with an acid buffer) and b are 2 1 B 2 ribosomes (with an acid buffer).
  • C is 21 B 2-TF ribosome (without washing with acid buffer)
  • d is 21 B 2-TF ribosome (with acid buffer)
  • E) indicates TF ribosome (without washing with an acid buffer)
  • f indicates TF ribosome (after washing with an acid buffer).
  • Fig. 4 shows the results of flow cytometer measurements showing the response of each ribosome to human osteoblastic tumor cell line K562.
  • the vertical axis in the figure shows the fluorescence shift (amount of ribosome bound to the cells) of the flowmeter, and the average value of the histogram.
  • Nega is the value of only those cells that do not react with the ribosome
  • TF — is the PEG unmodified TF ribosome
  • TF + is the PEG-modified TF ribosome.
  • 21B2TF— indicates PEG-unmodified 21 B2—TF liposome
  • 21B2TF + indicates PEG-modified 21B2—TF liposome.
  • microparticles are obtained by the association of amphipathic molecules containing a lyophilic part and a lyophobic part in the molecule.
  • Weights double-cell membrane vesicles such as micelles, macromolecular micelles, microspheres, emajoryons, ribosomes and ribosomes.
  • a polymer S preferably a micelle, in which the resulting polymer vesicles and the like are obtained.
  • Such micelles can take the form of small spheres, ellipsoids or long cylinders composed of amphiphiles. For example, those containing ribosomes, no Vasosomes, and non-active IJ vesicles, but which are more suitably used. It is a liposome.
  • the amphipathic molecules that make up the micelles contain a lyophilic and a lyophobic part, which is in a manner known per se and known in the art. Any substance that can form micelles can be used, and the preferred amphiphilic substance among these is lunar The power to raise quality.
  • the lipids that can constitute the micelles of the present invention include, for example, natural lecithin (eg, egg yolk lecithin, soy lecithin, etc.). ) ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ D D D D D
  • lipids such as luamine (DOPE), sugar lipids such as glycosphingolipids, glycephalic lipids, etc., phosphorus lipids, cholesterol, Polyethylene glycol inducers, such as fatty acids, can be mentioned. These lipids may be used alone or in combination of two or more, or in combination with nonpolar substances such as cholesterol. .
  • the micelles and liposomes are made by such a method.
  • it can be manufactured by using a known manufacturing technique known in the art: for example, a thin grease attached to a glass wall.
  • Multi-lamellar vosor (MLV) which is formed by adding a water solution to the membrane and mechanically shaking it, as well as ultrasonic treatment and ethanol injection , Smo-Luni lamellar ribosome (SJV) obtained by the french-press method, removal of surfactant, and reverse-phase evaporation (Ribosome Sunamoto et al. 19988), an extruder that extrudes an MLV by pressing a membrane with a uniform bore diameter.
  • LUVs large-sized lamellar liposomes obtained from the Zion method or the like (Liposome Technology, Vol. 1 2 ndedition) c
  • microparticles of the present invention include a complex composed of a gene and a polypeptide, a gene composed of a polypeptide, a polypeptide, and a fatty acid. You can use a complex consisting of a complex, or a complex consisting of a gene, a polypeptide, and a ribosomal force.
  • the cell-bound ligand (A) has a binding property to a target molecule present on the cell surface. However, they are not actually taken up by cells that are actually targets, and specifically exist on the cell surface.
  • the antibody is selected from proteins such as EGF, VEGF, HGF, etc., folate, lectin, sugar chains, vitamins, etc., which are preferred. It is an antibody.
  • the anti-human chimera antibody, the humanized antibody, and the human anti-body strength are preferable to use.
  • Antibody fragments, such as F (ab ') 2 conjugated antibodies, obtained by pepsin treatment, etc., and scFV can be used as a whole.
  • Ligand (A) can be combined with fine particles via covalent bond and the force S can be any known bond bonding method. It is possible to use the carbodiimide method, maleimide method, periodate method, etc.
  • an active group such as a thiol group is introduced into the ligand (A), and a maleimid group or a pyridyl group is added to fine particles such as a ribosome.
  • a base such as a disulphide group
  • the ligand (A) may be directly bonded to the fine particles, or may be bonded to the fine particles through a part of the spacer, or may be connected to the fine particles. Normally, virtually all of the legs are joined together through a splicer, either by joining the types or by combining them.
  • These spacers are usually polyacrylamide, polyvinylpyrrolidone, polyamino acid, polylactic acid, and polylactic acid.
  • Water-soluble polymers such as glycerin, poly (colic acid), polysaccharides, or poly (alkylene glycol) derivatives are typical. As mentioned above, it is preferably a polyalkylene glycol, especially a polyethylene glycol (PEG) inducer. .
  • Japanese Patent Laid-Open Publication No. 6-126206 Use the methods disclosed in the 70 bulletin, BBA 1 239 (1995) 1 33, etc., in particular; This is a method using the PEG derivative shown in JP-A-11-152.
  • the molecular weight of the prober is about 500 to 500, but preferably about 100 to 100. Yes, more preferably about 20000 to 60000.
  • the ligand (A) can exert a force S that combines 0.1% to 20% (W / W) of the fat mass of the fine particles. Preferably, it is 0.5 to 10% and more preferably 1 to 5%.
  • an active ligand is a machine that is incorporated into a cell that is a target.
  • Any EGF receptor, transfucco: lin receptor, HGF receptor can be used as long as it has the function.
  • Antibodies to, etc., their antibody fragments, including some of them ⁇ Substances derived from antibodies, such as peptides, transphenylene, EGF , Proteins such as HGF, FGF, TGF, etc .; sugars of mannose sugar; complex saccharides such as LPS; lipids such as LDL; and low molecular compounds such as folic acid (preferred).
  • Ligand (B) can be bound to the microparticles in the same manner as the above-mentioned ligand (A), but via a spacer.
  • the direct binding to the microparticles, and the force S preferred, is from 0.1 % to 20 % of the lunar mass of the microparticles (B).
  • WZW can be combined with a force S, preferably from 0.5 to 10%, and more preferably from 1 to 5%.
  • Fine particles can be combined with a water-soluble polymer (C) in addition to a ligand.
  • This water-soluble polymer (C) is the same as the water-soluble polymer used as the aforementioned spacer, and is a polyacrylamide.
  • Polyvinylpyrrolidone, polyamino acid, polylactic acid, polyglycerin, polyglycolic acid, polysaccharides, polyphenols The ability to raise water-soluble polymers such as dielectric conductors; preferably, polyalkylene glycol, especially
  • the water-soluble polymer (c), which is a derivative of polyethylene glycol (PEG), is the same as the water-soluble polymer used as a spacer.
  • the water-soluble polymer used as a spacer must have a function that binds to both the ligand and the fine particles.
  • the water-soluble polymer (C) is used to disperse the ligand (A) into fine particles that need to be capable of binding to the ligand. Bonding through a child can effectively bind the fine particle-ligand complex to target cells, but it has the effect of using a ligand.
  • water-soluble polymer (C) By binding water-soluble polymer (C) to microparticles, which is not capable of binding to metal, it has the function of being incorporated into cells. Reduce non-specific binding of the ligand (B) As a result, an effect is produced, and improvement in stability in living organisms is expected.
  • the molecular weight of the water-soluble polymer (C) is in the range of about 500 to about 500,000, preferably about 100,000. It is about 0, and more preferably about 20000 to about 60000.
  • This water-soluble polymer (C) can be introduced either after the ligand is bonded to the fine particles or at the same time as the ligand. it can .
  • RevoSom is used as microparticles, as disclosed in the official gazette of Japanese Patent Publication No. 4-346991, After combining a ligand with a chonole group to a ribosome with a mid group, a polyalkyl with a further carbon group is bonded.
  • Compound containing len component PE
  • G inducer can be used to give the leg and PEG.
  • the lipid derivative of the ligand and the lipid derivative of PEG are used at the same time to form the liposome by the method of removing the surfactant. This makes it possible to create a liposome with a ligand and PEG.
  • the particles (A), which are capable of binding to cells, are bound to the cells via the water-soluble polymer, and are incorporated into the cells.
  • functionally capable ligands (B) and further modifying the microparticles with water-soluble polymers (C) it is no longer necessary.
  • the water-soluble polymer (C) is 2 to 100%, preferably 3 to 50%, more preferably 5 to 5, based on the fat mass of the fine particles.
  • the force S can be used at 10% of the force.
  • the microparticles of the present invention contain a drug or a diagnostic agent, but the microparticles can be introduced into the microparticles.
  • Pharmaceutical products include, for example, anti-adriamycin, downomycin, vinblastine, cis-bratin, and 5-FU.
  • Tumor agents such as Timol
  • high blood pressure drugs such as clodinine
  • antiemetic drugs such as proline, quinone mouth quinine, etc.
  • Anti-malarial agents, their pharmaceutically acceptable salts and derivatives, and toxic proteins such as ricin A chain and diphtheria toxin Quality and the genes that code for them, antisense such as k-ras, HSV—TK and P53,
  • TNF, GM Genes encoding CSF, etc., as well as complexes and inducers of such genes with polycations such as poly- lysines, etc. Radioactive isotopes such as de, linium, and yttrium, and compounds for neutron capture therapy, such as sodium borocaptate, are mentioned.
  • the present onset Ming range is c real not name a child that will be the implementation example limit constant of the following Examples
  • Anti-CEA mouse monoclonal antibody dissolved in 50 mM phosphoric acid buffer 1 mM EDTA (pH 7.0) 2
  • the PEG derivative (Ac-S-PEG-Sue) described in 22 3 4 was added with 30 mg / ml.
  • the PEG derivative (Ac-S-PEG-Suc) described in JP-A No. 1- 1 5 2 2 3 4 was synthesized by the following method.
  • SP Sepharose (2 mlbed) (equilibrated with 0.1 M acetic acid buffer (pH 4)) (After loading with this buffer and washing with the buffer, mM Myonic acid buffer 1 m MEDTA (p
  • 50 mM phosphoric acid buffer solution 1 M MEDTA (pH 7.0) was dissolved in human trans-ferrin (Sigma 5 mg / m 1). Acetylthioglycol dissolved in ethanol n-Monoleic acid N—Hydroxylsuccinimide ester (Sigma) 200 / After adding ig and reacting at 25 ° C for 1 hour, 50 mM phosphoric acid buffer 1 m MEDT The salt was desalted with PD-10 equilibrated with A (pH 7.0). A 1/9 volume of hydroxylene oleamine solution (0.5 M hydroxylene) was added to the modified trans phenylene solution collected in the void area.
  • RevoSom is Ginomi Toilet Foil Fat Collin (DPPC) / Cholesterol Z Male Mitsile Fossil Fuel Ethanol Amine (Publication No. 4-13461918 Publication) 18Z10Z0.5 (Mole ratio) It was made from a mixture of various fats, ie, 1 OmM of this mixture was mixed with 1 OmM of carboxyl fluorescein in water. A multi-lamellar liposome was prepared by hydrating 1 m1 of the liquid and then using an eX truder (Lipex Biomembranes) with a 0.1 ⁇ m The granules were sized with a poly-one membrane.
  • DPPC Ginomi Toilet Foil Fat Collin
  • Cholesterol Z Male Mitsile Fossil Fuel Ethanol Amine Publication No. 4-13461918 Publication
  • 18Z10Z0.5 Mole ratio
  • the human gastric carcinoma cell line MKN45 was cultured in 8-well tannin slide until partial pile-up, and the lipid concentration was determined. 1 mg Zm1 PEG-modified 2 1 B2 — TF liposome, PEG-modified 21 B2 ribosome, PEG-modified TF ribosome The reaction was carried out for 1 hour with ice cooling. After completion of the reaction, wash and remove the liposome solution, replace with 10% (V / V) FBS-added medium, and incubate at 37 ° C for 1 hour. It was uploaded. After incubating, the cells are washed with ice-cold PBS-Az, and ribosomes are more clearly identified inside and outside the cells.
  • TF liposomes shown in Example 1 and Example 2 human bone was used. The responsiveness of each ribosome to blastoma cell line K5662 was measured. TF and 2 1 B 2 The amount bound to the liposomes was comparable with or without PEG.
  • Human osteoblastic tumor cell line K562 (high expression of TF receptor, weak expression of CEA: confirmed by FACScan) was taken in a 1.5 ml tube, and oil was taken. Concentration of 1 mg Z ml 2 1 B2 — TF ribosome, PEG-modified 21 B2 — TF liposome, TF ribosome, PEG-modified TF ribo Each room was reacted for 1 hour with ice cooling under light shielding. After the reaction is completed, the cells are washed with PBS-Az and passed through a filter with a pore size of 35 ⁇ m. I used it to pray.
  • the PEG modification suppresses the binding activity of TF directly bound to the ribosome, while the TF is bound to the leading end of the PEG spacer.
  • the binding activity of the 21B2 antibody had almost no effect on the binding activity of the 21B2 antibody. This reflects the uniqueness of the ligand binding to the target via the PEG spacer to the liposome. It is shown that while it is possible to reduce the responsiveness of the transponder directly connected to the liposome. Trans-ferrin is also present in many normal cells, and this is to suppress undesired non-specific reactions. Show and review.
  • Ligand that binds to the target cell on the microparticles (A) and is active in its incorporation into the target cell By applying (B) to the target cell [1], it is possible to obtain a target cell with extremely low incorporation capability only with the ligand (B) alone. In addition, it was found that the uptake of the cells in both cells was high by giving both of them the ligand.

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Abstract

L'invention concerne des fines particules dans lesquelles un ligand capable de se lier à des cellules cibles est directement ou indirectement lié à un autre ligand pouvant être incorporé dans lesdites cellules. Ces particules fines sont notamment utilisées pour l'administration de médicaments, etc.
PCT/JP2000/002272 1999-04-08 2000-04-07 Particules fines ciblant des cellules, et procede de production correspondant WO2000061114A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU36735/00A AU3673500A (en) 1999-04-08 2000-04-07 Fine particles targeting cells and process for producing the same

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Application Number Priority Date Filing Date Title
JP11/101020 1999-04-08
JP10102099 1999-04-08

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WO2000061114A1 true WO2000061114A1 (fr) 2000-10-19

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006089471A (ja) * 2004-08-26 2006-04-06 National Institute Of Advanced Industrial & Technology 癌の治療における抗モータリン２抗体と機能性核酸の使用
WO2006126267A1 (fr) * 2005-05-26 2006-11-30 Mebiopharm Co., Ltd. Procede de transfert de gene
WO2007088952A1 (fr) * 2006-01-31 2007-08-09 Taiho Pharmaceutical Co., Ltd. Preparation de liposome comprenant une substance ayant une action anticancereuse
JP4754136B2 (ja) * 1999-06-28 2011-08-24 モザイク ディスカバリー リミテッド 結合補助体の非共有結合会合で形成されるエピトープ
WO2020144467A1 (fr) * 2019-01-07 2020-07-16 Ucl Business Ltd Polymersomes fonctionnalisés dotés de multiples ligands

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Publication number Priority date Publication date Assignee Title
EP0520499A1 (fr) * 1991-06-28 1992-12-30 Mitsubishi Chemical Corporation Anticorps humain monoclonal spécifique à l'antigène de surface de la membrane des cellules cancéreuses
JPH09110722A (ja) * 1995-10-20 1997-04-28 Toray Ind Inc 抗腫瘍活性物質の腫瘍細胞内導入用イムノリポソーム及びその調製法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0520499A1 (fr) * 1991-06-28 1992-12-30 Mitsubishi Chemical Corporation Anticorps humain monoclonal spécifique à l'antigène de surface de la membrane des cellules cancéreuses
JPH09110722A (ja) * 1995-10-20 1997-04-28 Toray Ind Inc 抗腫瘍活性物質の腫瘍細胞内導入用イムノリポソーム及びその調製法

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Title
KIRPOTIN,D.ET AL: "Sterically Stabilized Anti-HER2 Immunoliposomes: Design and Tagetting to Human Breast Cancer Cells in Vitro", BIOCHEMISTRY, vol. 36, no. 1, 1997, CALIFORNIA USA, pages 66 - 75, XP002929568 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4754136B2 (ja) * 1999-06-28 2011-08-24 モザイク ディスカバリー リミテッド 結合補助体の非共有結合会合で形成されるエピトープ
JP2006089471A (ja) * 2004-08-26 2006-04-06 National Institute Of Advanced Industrial & Technology 癌の治療における抗モータリン２抗体と機能性核酸の使用
WO2006126267A1 (fr) * 2005-05-26 2006-11-30 Mebiopharm Co., Ltd. Procede de transfert de gene
WO2007088952A1 (fr) * 2006-01-31 2007-08-09 Taiho Pharmaceutical Co., Ltd. Preparation de liposome comprenant une substance ayant une action anticancereuse
JP4881327B2 (ja) * 2006-01-31 2012-02-22 大鵬薬品工業株式会社 抗腫瘍活性物質のリポソーム製剤
WO2020144467A1 (fr) * 2019-01-07 2020-07-16 Ucl Business Ltd Polymersomes fonctionnalisés dotés de multiples ligands
US12257344B2 (en) 2019-01-07 2025-03-25 Ucl Business Ltd Polymersomes functionalised with multiple ligands

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