JP2008105961A - Arylmethylamine derivative and its salt, and medicine carrier comprising the same as its constituent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an arylmethylamine derivative and a salt thereof as a cationized lipid capable of forming a medicine carrier that can efficiently and safely achieve transfection of a nucleic acid into a cell and delivery of a medicine to an aimed part, and a medicine carrier comprising the same as its constituent. <P>SOLUTION: The medicine carrier comprises as its constituent the arylmethylamine derivative represented by formula (1) or a salt thereof. In formula (1), A is an aromatic ring; R1 and R2 are each independently a 10-14C alkyl or alkenyl group; and X and Y are each independently either one group selected from the group consisting of O, S, COO, OCO, CONH and NHCO. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

The present invention relates to a novel arylmethylamine derivative and a salt thereof, and a drug carrier containing it as a constituent component.

In recent years, research has been actively conducted to apply closed vesicles such as liposomes, emulsions, and lipid microspheres to drug delivery systems (hereinafter referred to as DDS) as drug carriers. These closed vesicles are generally prepared using phospholipids or derivatives thereof, or sterols or lipids other than phospholipids as basic membrane constituents. However, these basic constituents alone could not overcome difficulties in various aspects such as aggregation between closed vesicles and reduction in retention in the body. Furthermore, it was very difficult to actually reach the target site as a DDS preparation.

Therefore, for the purpose of improving the drug encapsulation rate and the cell adhesion of closed vesicles, a small amount of cationized lipid such as stearylamine is incorporated as a constituent component to make the surface of closed vesicles cation in a physiological pH range. Attempts have also been made. In particular, cationic liposomes containing DNA are known to promote the transfer (transfection) of DNA into cells, but are further desired to have high introduction efficiency, expression rate, and safety.
However, lipids that can be selected as cationized lipids are limited, and there is a strong demand for the development of cationized lipids for drug carriers that exhibit high safety and high functionality. At present, as such cationized lipids, for example, those described in Patent Documents 1 to 4 have been reported, but sufficient effects have not been obtained.

U.S. Pat. No. 4,897,355 US Pat. No. 5,337,761 JP-A-2-292246 JP-A-4-108391

Therefore, DNA can be efficiently and safely introduced into cells, and in addition to the movement of DNA into cells, for example, vascular endothelial injury site, nephritis, kidney cancer, pneumonia, lung cancer, hepatitis, liver cancer, pancreatic cancer Therefore, there is a strong demand for the development of a drug carrier that can efficiently and safely target a drug to an affected area such as lymphoma and is effective for DDS therapy.

The present invention has been made in view of such problems, and can form a drug carrier capable of efficiently and safely introducing a nucleic acid into a cell (transfection) and delivering the drug to a target site. It is an object of the present invention to provide arylmethylamine derivatives and salts thereof as cationized lipids, and drug carriers containing them as constituents.

As a result of intensive research, the present inventors have met the above object when an amphiphilic arylmethylamine derivative having an alkyl group or an alkenyl group having 10 to 14 carbon atoms and a salt thereof are used as a cationized lipid. The present inventors have found that a drug carrier can be formed and have completed the present invention.

The arylmethylamine derivative and the salt thereof according to the first invention meeting the above object are an arylmethylamine derivative and a salt thereof represented by the following general formula (1).

In the formula (1), A represents an aromatic ring, R1 and R2 each independently represent an alkyl group or alkenyl group having 10 to 14 carbon atoms, and X and Y each independently represent O, S And represents any one group selected from the group consisting of COO, OCO, CONH, and NHCO.

The arylmethylamine derivative and the salt thereof according to the first invention may be an arylmethylamine derivative represented by the following formula (2) and a salt thereof.

The drug carrier according to the second invention is composed of a molecular assembly comprising as constituent components an arylmethylamine derivative represented by the following general formula (3) and a salt thereof.

In formula (3), A represents an aromatic ring, R1 and R2 each independently represent an alkyl group or alkenyl group having 10 to 25 carbon atoms, and X and Y each independently represent O, S And represents any one group selected from the group consisting of COO, OCO, CONH, and NHCO.

In the drug carrier according to the second invention, the arylmethylamine derivative may be represented by the following formula (4).

In the drug carrier according to the second invention, it is preferable that a drug for performing one or both of diagnosis and treatment is enclosed in the drug carrier.

In the drug carrier according to the second invention, the drug may be any one or a plurality of nucleic acids, polynucleotides, genes and analogs thereof.

In the drug carrier according to the second invention, the drug is an anti-inflammatory agent, steroid agent, anticancer agent, enzyme agent, enzyme inhibitor, antibiotic, antioxidant, lipid uptake inhibitor, hormone agent, angiotensin converting enzyme inhibitor Angiotensin receptor antagonist, smooth muscle cell proliferation and migration inhibitor, platelet aggregation inhibitor, chemical mediator release inhibitor, vascular endothelial cell proliferation or inhibitor, aldose reductase inhibitor, mesangial cell proliferation inhibitor, Any one or more of a lipoxygenase inhibitor, an immunosuppressive agent, an immunostimulant, an antiviral agent, and a radical scavenger may be used.

In the drug carrier according to the second invention, the drug may be glycosaminoglycan and a derivative thereof.

In the drug carrier according to the second invention, the drug may be one or more of oligosaccharides, polysaccharides, and derivatives thereof.

In the drug carrier according to the second invention, the drug may be a protein or a peptide.

In the drug carrier according to the second invention, the drug may be one or more of an X-ray contrast agent, a radioisotope-labeled nuclear medicine diagnostic agent, and a diagnostic agent for nuclear magnetic resonance diagnosis.

In the drug carrier according to the second invention, the molecular assembly may have a spherical, cylindrical or rod-like structure having a size of 0.02 to 250 μm.

In the drug carrier according to the second invention, the molecular assembly may constitute a closed vesicle. Here, “closed vesicles” means liposomes, micelles, lipid microspheres and emulsions.

The drug carrier according to the second invention may contain any one or more of phospholipids and derivatives thereof, lipids and derivatives thereof other than phospholipids, stabilizers, antioxidants, and surface modifiers. .

Since the arylmethylamine derivative and the salt thereof according to the first invention are cationic lipids having the molecular structure represented by the formula (1), for example, a drug for performing either or both of diagnosis and treatment Can be formed into a drug carrier that can be efficiently and safely introduced into cells to be administered.
In particular, when the arylmethylamine derivative used as a cationized lipid and a salt thereof are the arylmethylamine derivative represented by the formula (2) and a salt thereof, the gene transfer is higher than that of a commercially available gene transfer reagent. A drug carrier having a function can be formed.

Since the drug carrier according to the second invention is composed of a molecular assembly comprising the arylmethylamine derivative represented by the general formula (3) and a salt thereof as a cationized lipid, the drug is to be administered. It can be efficiently and safely introduced into cells.
In particular, when the arylmethylamine derivative and the salt thereof, which are constituents of the drug carrier, are the arylmethyl derivative and the salt represented by the formula (4), the gene transfer ability is higher than that of a commercially available gene transfer reagent. Have

In the drug carrier according to the second invention, when a drug for performing either or both of diagnosis and treatment is enclosed in the drug carrier, a water-soluble drug or a high-molecular-weight drug that cannot pass through the cell membrane Can also reach the inside of the cell through membrane fusion between the cell membrane and the drug carrier.

In the drug carrier according to the second invention, when the drug is one or more of a nucleic acid, a polynucleotide, a gene and an analog thereof, the cause of the disease caused by administration of the deleted gene, RNA interference, etc. It is possible to safely and efficiently treat various genetic diseases through suppression of gene expression.

In the drug carrier according to the second invention, the drug is (1) an anti-inflammatory agent, a steroid agent, an anticancer agent, an enzyme agent, an enzyme inhibitor, an antibiotic, an antioxidant, a lipid uptake inhibitor, a hormone agent, an angiotensin converting enzyme Inhibitors, angiotensin receptor antagonists, smooth muscle cell proliferation and migration inhibitors, platelet aggregation inhibitors, chemical mediator release inhibitors, vascular endothelial cell growth or inhibitors, aldose reductase inhibitors, mesangial cell growth inhibitors Any one or more of agents, lipoxygenase inhibitors, immunosuppressants, immunostimulants, antiviral agents, and radical scavengers, (2) glycosaminoglycans and derivatives thereof, (3) oligosaccharides, polysaccharides, and these Any one or more of (1) or (4) either protein or peptide If that is, these drugs by administering only the target cells, it is possible to suppress side effects to enhance the therapeutic effect.

In the drug carrier according to the second invention, when the drug is one or more of an X-ray contrast agent, a radioisotope-labeled nuclear medicine diagnostic agent, and a diagnostic agent for nuclear magnetic resonance diagnosis, these diagnostic agents are used. By administering only to the target cells, the labeling effect can be enhanced and the adverse effects on the cells due to radiation or the like can be minimized.

In the drug carrier according to the second invention, when the molecular assembly has a spherical, cylindrical, or rod-shaped structure having a size of 0.02 to 250 μm, depending on the type of drug, the administration target site, etc. A drug carrier having an optimal size and shape can be selected, and the pharmacokinetics of the drug can also be controlled.

In the drug carrier according to the second invention, when the molecular assembly constitutes closed vesicles, both water-soluble and fat-soluble drugs can be encapsulated inside the drug carrier.

When the drug carrier according to the second invention contains one or more of phospholipids and derivatives thereof, lipids and derivatives thereof other than phospholipids, stabilizers, antioxidants, and surface modifiers Can improve the stability of the drug carrier.

Subsequently, an embodiment of the present invention will be described to provide an understanding of the present invention.
An arylmethylamine derivative and a salt thereof according to an embodiment of the present invention are represented by the formula (1), and can be produced, for example, by a reduction reaction of an aryl nitrile derivative represented by the formula (5).

In the formulas (1) and (5), A represents an aromatic ring, R1 and R2 each independently represents an alkyl group or an alkenyl group having 10 to 14 carbon atoms, and X and Y are each independently And represents any one group selected from the group consisting of O, S, COO, OCO, CONH, and NHCO.
Specific examples of the aromatic ring A include benzene, pyridine, biphenyl, bipyridyl, naphthalene, quinoline, anthracene, phenanthrene, and acridine, and benzene is preferred.
Further, both X and Y are preferably O. R1 and R2 are preferably a linear alkyl group, more preferably a linear alkyl group having 12 to 14 carbon atoms.

Synthetic methods of aryl nitrile derivatives as raw materials include dehydration reaction of carboxylic acid amides with phosphorus oxychloride, reaction of aromatic diazonium salt with cuprous cyanide (Sandmeyer reaction), aromatic nucleophilic substitution of aryl halides Reaction etc. are mentioned.
Examples of the reducing agent that can be used include lithium aluminum hydride (LiAlH ₄ ).

The arylmethylamine derivative thus produced can be isolated and collected by means of separation and purification means known per se (for example, chromatography, recrystallization) and the like.

Here, the arylmethylamine derivative can also be used as a salt in which an amino group is protonated. Any salt that does not interfere with the formation of the drug carrier and encapsulating the drug inside thereof and does not have harmful effects on adults such as cytotoxicity can be used. Specific examples include hydrochloride, hydrobromic acid Examples thereof include salts, sulfates, nitrates, carbonates, phosphates, acetates, citrates and lactates.

The drug carrier is a molecular assembly having a size of 0.02 to 250 μm, preferably 0.05 to 0.4 μm.
As the structure of the molecular assembly, various forms such as a spherical shape, a cylindrical shape, and a rod shape are conceivable, and it is not necessary to limit, but in particular, a closed vesicle capable of encapsulating a high concentration of drug therein, that is, It is most desirable to take at least one or more of liposomes, micelles, lipid microspheres (fat emulsion) and emulsions (O / W type and W / O type).

As a component of the drug carrier other than the arylmethylamine derivative, formation of a molecular assembly, encapsulation of the drug inside the molecular assembly, and introduction of the drug into the cell via lipid exchange, endocytosis, etc. Any one or more types of lipids or derivatives thereof that can be preferred. The lipid may be naturally derived or chemically synthesized, and an amphiphilic compound having any structure other than fatty acid triglyceride and phospholipid can be used. Particularly preferred are phospholipids or derivatives thereof which are constituents of the membrane.

As phospholipids, phosphatidylcholine (= lecithin), phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, cardioribine, or the like according to conventional methods Examples include hydrogenated ones.

The types of lipids used as components other than arylmethylamine derivatives and the composition ratio of each lipid when used in combination with multiple types of lipids depend on the type of drug to be encapsulated, the site of drug delivery, the conditions used, etc. It is difficult to determine unambiguously because it depends, but it is adjusted as appropriate so that a molecular assembly (drug carrier) having the desired shape and size can be stably formed. The composition ratio of the arylmethylamine derivative and other lipids enables efficient encapsulation of the drug and introduction of the drug into the cell, and does not interfere with the formation of the drug alone or develop cytotoxicity. It is adjusted appropriately within the range.

For example, when encapsulating DNA as a drug, it is preferable to use dioleoylphosphatidylethanolamine (DOPE) and dilauroylphosphatidylcholine (DLPC) in combination as lipids other than arylmethylamine derivatives. The molar ratio of the arylmethylamine derivative to DOPE and DPLC is preferably in the range of 1: 0.4 to 2.2: 0.9 to 1.1. The mole ratio of the arylmethylamine derivative, DOPE and DLPC Most preferred is a ratio of 1: 1 to 2: 1.

In addition, one or both of a stabilizer and an antioxidant may be added to improve the storage stability of the drug carrier and enhance the stability at the time of administration. You may add the surface modifier for improving (what is called stealth property).

Stabilizers include sterols such as cholesterol that reduce membrane fluidity, or sugars such as glycerol and sucrose.
Examples of the antioxidant include a tocopherol homologue, that is, vitamin E. There are four isomers of tocopherol, α, β, γ, and δ, and any isomer can be used.
Examples of the surface modifier include hydrophilic polymers and derivatives of water-soluble polysaccharides such as glucuronic acid, sialic acid, and dextran.

Examples of hydrophilic polymers include polyethylene glycol, dextran, pullulan, ficoll, polyvinyl alcohol, styrene-maleic anhydride alternating copolymer, divinyl ether-maleic anhydride alternating copolymer, synthetic polyamino acid, amylose, amylopectin, chitosan, Mannan, cyclodextrin, pectin, carrageenan and the like can be mentioned. Among them, polyethylene glycol is most preferable because it has a remarkable effect of improving the blood retention.

The hydrophilic polymer may be a derivative of a hydrophobic compound such as a long chain aliphatic alcohol, a sterol, a polyoxypropylene alkyl, or a glycerin fatty acid ester, and a hydrophobic carrier such as a liposome. ) Can be stably inserted into the membrane. Thereby, a hydrophilic polymer can be present on the surface of the drug carrier. Specific examples of preferable hydrophilic polymer derivatives that can be used include polyethylene glycol-phosphatidylethanolamine and the like.

As a drug encapsulated in a drug carrier, a pharmaceutically acceptable pharmacologically active substance, physiologically active substance or diagnostic substance can be used depending on the purpose of either or both of diagnosis and treatment.
The substance to be encapsulated may be basically any substance, but since the surface of the carrier has a positive charge, a substance that is electrically neutral or anionic is more likely to have electrostatic repulsion. Therefore, a higher encapsulation rate can be expected.

Of the drugs used for treatment, the type of drugs that can be encapsulated in the drug carrier is not particularly limited as long as it does not interfere with the formation of the drug carrier. Specifically, nucleic acids, polynucleotides, genes and analogs thereof, anti-inflammatory agents, steroid agents, anticancer agents, enzyme agents, enzyme inhibitors, antibiotics, antioxidants, lipid uptake inhibitors, hormone agents, angiotensin converting enzyme Inhibitors, angiotensin receptor antagonists, smooth muscle cell proliferation and migration inhibitors, platelet aggregation inhibitors, chemical mediator release inhibitors, vascular endothelial cell proliferation promoters or inhibitors, aldose reductase inhibitors, mesangial cell proliferation Inhibitors, lipoxygenase inhibitors, immunosuppressants, immunostimulators, antiviral agents, radical scavengers, glycosaminoglycans and derivatives thereof, oligosaccharides, polysaccharides, derivatives thereof, proteins, peptides and the like.

In addition, among the drugs used for diagnosis, the type of drugs that can be encapsulated in the drug carrier is not particularly limited as long as the formation of the drug carrier is not hindered. Specific examples include X-ray contrast agents, radioisotope-labeled nuclear medicine diagnostic agents, diagnostic agents for nuclear magnetic resonance diagnosis, and the like.

The drug carrier can be easily prepared by a conventional method, and one embodiment thereof is shown below. In the flask, the arylmethylamine derivative represented by the general formula (1) and other carrier components such as phospholipids are mixed with an organic solvent such as chloroform, and the organic solvent is distilled off and then vacuum-dried to the inner wall of the flask. A thin film is formed. Next, a drug is added to the flask and vigorously stirred to obtain a liposome dispersion. The obtained liposome dispersion is centrifuged, and the supernatant is decanted to remove the unencapsulated drug, whereby a drug carrier can be obtained as a dispersion. Moreover, it can also obtain by mixing each said component and carrying out high pressure discharge with a high pressure discharge type emulsifier.

EXAMPLES Next, although an Example is given and this invention is demonstrated in more detail, this invention should not be limited to these Examples and a test example.
Note that “liter” is written using the capital letter “L”.

Example 1: 3,5-disilazide de siloxy benzylamine in the synthesis eggplant flask (a X = Y = O, R1 = R2 = C 12 H 25, formula (arylmethyl derivative represented by 2)) A mixture of 1.01 g of 3,5-dihydroxybenzonitrile, 3.80 g of 1-bromododecane, 2.13 g of potassium carbonate and 25 mL of N, N-dimethylformamide was stirred at 60 ° C. overnight, and then water was added to precipitate. The obtained solid was collected by filtration and washed with methanol and hexane. The crystals obtained here were dried in a desiccator under reduced pressure, dissolved in a mixed solvent of chloroform and ethanol, activated carbon was added at around the reflux temperature, refluxed, the activated carbon was removed by filtration and allowed to stand overnight. The precipitated crystals were collected by filtration and dried in a desiccator under reduced pressure to obtain 2.14 g of 3,5-didodecyloxybenzonitrile. Next, after replacing the nitrogen in a three-necked flask equipped with an equal pressure dropping funnel and a nitrogen balloon, 15 mL of diethyl ether was added and cooled to 0 ° C., and then 0.12 g of lithium aluminum hydride was added. A solution prepared by dissolving 1.03 g of 3,5-didodecyloxybenzonitrile in 5 mL of diethyl ether was added and stirred for 30 minutes. H ₂ O / THF (1/1, v / v) solution and 15% NaOH aqueous solution were added to the reaction solution. Celite was placed on a glass filter, and the residue was filtered off. The filtrate was transferred to a separatory funnel, ethyl acetate was added, and the organic layer and the aqueous layer were separated. The organic layer was washed with saturated brine, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was purified by silica gel column chromatography to obtain 0.44 g of 3,5-didodecyloxybenzylamine. ¹ H-NMR (CDCl ₃ ) δ (ppm): 6.44 (s, 2H), 6.33 (s, 1H), 3.93 (t, 4H, J = 6.6 Hz), 3.79 ( s, 2H), 1.73-1.79 (quant, 4H, J = 6.9 Hz), 1.13-1.49 (m, 36H), 0.88 (t, 6H, J = 6.6 Hz) )

Example 2: 3,5-di-penta de siloxy benzylamine synthetic gene transfer efficiency (X = Y = O, a _{R1 = R2 = C 15 H 31} , formula (arylmethyl derivative represented by 2)) For comparison, 3,5-dipentadecyloxybenzylamine was synthesized in the same manner as in Example 1.

Example 3: Preparation of lipid DNA complex Lipid DNA complex (liposome), which is an example of a drug carrier containing 3,5-didodekioxybenzylamine prepared in Example 1 as a constituent and encapsulating DNA as a drug Plex) was prepared as follows.
Each lipid solution obtained by dissolving a lipid powder of 3,5-didodecyloxybenzylamine, DOPE (dioleoylphosphatidylethanolamine, DLPC (dilauroylphosphatidylcholine) in a chloroform solution to a concentration of 0.1 μmol / 10 μL is 3 , 5-didodecyloxybenzylamine: DOPE: DLPC = 1: 2: 1 (total lipid amount: 3.2 μmol) The solvent was distilled off using an evaporator to form a lipid thin film. PBS (1 mL) was added, and the mixture was heated to 60 ° C. and dispersed with an ultrasonic irradiation device to obtain a liposome dispersion, and then 1 mL of an aqueous solution in which 20 μg of plasmid DNA (pGL3) incorporating the luciferase gene was dissolved was added to the above solution. By mixing with the liposome dispersion prepared in The port plex was prepared.
A lipid DNA complex containing 3,5-dipentadecyloxybenzylamine prepared in Example 2 as a constituent component was also prepared in the same manner.
Further, for comparison, a lipid DNA complex comprising, as a constituent, Lipofectamine 2000 (trade name: Invitrogen), which is a commercially available polyamine-based gene introduction reagent as a cationized lipid instead of an arylmethylamine derivative, and a control A lipid DNA complex containing no cationized lipid was prepared using the same method as in this example.

Example 4: Gene introduction into Hep G2 cells using lipid DNA complex A 96-well plate (manufactured by Falcon) was prepared at 1 × 10 ⁵ cells / mL in 10% FBS (fetal bovine serum) -containing MEM medium. Hepatocellular carcinoma Hep G2 cells (available from Japan Cancer Research Bank) were seeded 100 μL each, and a suspension of lipid DNA complex prepared in Example 3 (liposome containing 0.2 μg of plasmid DNA (pGL3)) was added. . Then, cultured for 48 hours in a CO ₂ incubator, was replaced with fresh medium. After further incubation for 24 hours, the plate was washed with PBS. The cells were lysed, the substrate was added, and the luminescence amount of the enzyme reaction product was measured with a plate reader to determine the luciferase activity. Normalization between wells was performed by quantifying the total amount of protein in the cell lysate. The results are shown in FIG. In FIG. 1, “control” is the experimental result using a lipid DNA complex not containing a cationized lipid, and “C12”, “C15”, and “LP” are 3,5-5- The experimental result using the lipid DNA complex containing didodecyloxybenzylamine, 3, 5- dipentadecyloxybenzylamine, and Lipofectamine 2000 is shown. In addition, “RLU” means a relative light unit (relative light units).
As shown in FIG. 1, a lipoplex containing 3,5-didodecyloxybenzylamine (C12) and 3,5-dipentadecyloxybenzylamine (C15) is a lipoplex containing Lipofectamine 2000 (LP). Compared to that, it showed stronger activity.

It is a graph which shows the gene expression level in the Hep G2 cell which introduce | transduced the luciferase gene using various drug carriers.

Claims (14)

An arylmethylamine derivative represented by the following general formula (1) and a salt thereof.

In the formula (1), A represents an aromatic ring, R1 and R2 each independently represent an alkyl group or alkenyl group having 10 to 14 carbon atoms, and X and Y each independently represent O, S And represents any one group selected from the group consisting of COO, OCO, CONH, and NHCO. The arylmethylamine derivative and its salt according to claim 1, wherein the arylmethylamine derivative and its salt are represented by the following formula (2).

A drug carrier comprising a molecular assembly comprising an arylmethylamine derivative represented by the following general formula (3) and a salt thereof as a constituent component.

In formula (3), A represents an aromatic ring, R1 and R2 each independently represent an alkyl group or alkenyl group having 10 to 25 carbon atoms, and X and Y each independently represent O, S And represents any one group selected from the group consisting of COO, OCO, CONH, and NHCO. The drug carrier according to claim 3, wherein the arylmethylamine derivative is represented by the following formula (4).

The drug carrier according to any one of claims 3 and 4, wherein a drug for performing one or both of diagnosis and treatment is enclosed in the drug carrier. 6. The drug carrier according to claim 5, wherein the drug is one or more of a nucleic acid, a polynucleotide, a gene and an analog thereof. The drug carrier according to claim 5, wherein the drug is an anti-inflammatory agent, a steroid agent, an anticancer agent, an enzyme agent, an enzyme inhibitor, an antibiotic, an antioxidant, a lipid uptake inhibitor, a hormone agent, an angiotensin converting enzyme inhibitor, Angiotensin receptor antagonist, smooth muscle cell proliferation and migration inhibitor, platelet aggregation inhibitor, chemical mediator release inhibitor, vascular endothelial cell proliferation or inhibitor, aldose reductase inhibitor, mesangial cell proliferation inhibitor, lipoxygenase A drug carrier which is one or more of an inhibitor, an immunosuppressant, an immunostimulant, an antiviral agent, and a radical scavenger. 6. The drug carrier according to claim 5, wherein the drug is glycosaminoglycan and a derivative thereof. The drug carrier according to claim 5, wherein the drug is one or more of oligosaccharides, polysaccharides, and derivatives thereof. 6. The drug carrier according to claim 5, wherein the drug is a protein or a peptide. 6. The drug carrier according to claim 5, wherein the drug is one or more of an X-ray contrast agent, a radioisotope-labeled nuclear medicine diagnostic agent, and a diagnostic agent for nuclear magnetic resonance diagnosis. The drug carrier according to any one of claims 3 to 11, wherein the molecular assembly has a spherical, cylindrical, or rod-shaped structure having a size of 0.02 to 250 µm. The drug carrier according to any one of claims 3 to 12, wherein the molecular assembly constitutes a closed vesicle. The drug carrier according to any one of claims 3 to 13, wherein any one or more of phospholipids and derivatives thereof, lipids and derivatives thereof other than phospholipids, stabilizers, antioxidants, and surface modifiers. Containing a drug carrier.

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