WO2010026781A1 - Particules, leur procédé de fabrication, et gels - Google Patents

Particules, leur procédé de fabrication, et gels Download PDF

Info

Publication number
WO2010026781A1
WO2010026781A1 PCT/JP2009/004421 JP2009004421W WO2010026781A1 WO 2010026781 A1 WO2010026781 A1 WO 2010026781A1 JP 2009004421 W JP2009004421 W JP 2009004421W WO 2010026781 A1 WO2010026781 A1 WO 2010026781A1
Authority
WO
WIPO (PCT)
Prior art keywords
polymer block
particles
hydrophilic
hydrophilic polymer
block copolymer
Prior art date
Application number
PCT/JP2009/004421
Other languages
English (en)
Japanese (ja)
Inventor
村上義彦
Original Assignee
国立大学法人東京農工大学
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 国立大学法人東京農工大学 filed Critical 国立大学法人東京農工大学
Publication of WO2010026781A1 publication Critical patent/WO2010026781A1/fr

Links

Images

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—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A61K9/1273—Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/008—Hydrogels or hydrocolloids

Definitions

  • the present invention relates to particles that can be used, for example, as a gel for adhesion to living tissue, a method for producing the same, and a gel.
  • Representative fine particles include liposomes, polymer micelles, and polymer particles.
  • Liposomes are vesicles formed by phospholipids that are constituents of biological membranes, and various hydrophilic drugs can be encapsulated in the vesicles. Furthermore, by changing the charge, particle diameter, lipid component of the liposome, or by binding substances such as antigens, antibodies, sugars, etc. to the liposome surface, it is possible to impart specificity to cells or tissues. The possibility of various substances as drug-carrying carriers is being investigated.
  • the polymeric micelle is an aggregate formed by self-aggregation of an amphiphilic block copolymer composed of a hydrophilic polymer block and a hydrophobic polymer block in water.
  • the hydrophobic inner core (core) and the hydrophilic outer shell (shell) form a clear double structure.
  • the inner core forms a non-aqueous microenvironment and can be used as a reservoir for hydrophobic substances.
  • the outer shell has a role of increasing the solubility of polymer micelles in water, and can treat a hydrophobic substance encapsulated in the inner core as if it were a hydrophilic substance.
  • the polymer micelle can be used as a drug holding carrier for administering a hydrophobic drug into the blood (Japanese Patent Laid-Open No. 2007-023023).
  • both liposomes and polymeric micelles have a problem of generally low structural stability.
  • the present invention has high structural stability, little variation in particle diameter, and can stably include the hydrophilic active substance in the state in which, for example, the activity of the hydrophilic active substance is maintained.
  • particles capable of sustained release of an active substance a method for producing the same, and a gel.
  • the particles according to one embodiment of the present invention include A first layer; A second layer located outside the first layer; Including The first and second layers each have an amphiphilic block copolymer comprising a hydrophilic polymer block and a hydrophobic polymer block; In the first layer, the hydrophilic polymer block is located on the inside, and the hydrophobic polymer block is located on the outside, In the second layer, the hydrophobic polymer block is located on the inner side and the hydrophilic polymer block is located on the outer side.
  • the above particles may further contain a hydrophilic active substance.
  • the amphiphilic block copolymer contained in the first layer may have a weight average molecular weight of 1,000 to 20,000.
  • the amphiphilic block copolymer contained in the second layer may have a weight average molecular weight of 1,000 to 20,000.
  • the hydrophilic polymer block may have a reactive functional group.
  • the gel according to another embodiment of the present invention includes the above particles and a hydrophilic polymer.
  • the gel can be used for adhesion to living tissue.
  • the method for producing particles according to another aspect of the present invention includes: Emulsifying an organic solvent dispersion comprising an amphiphilic block copolymer comprising a hydrophilic polymer block and a hydrophobic polymer block and water to prepare a w / o emulsion; Emulsifying an aqueous dispersion comprising the w / o emulsion, an amphiphilic block copolymer comprising a hydrophilic polymer block and a hydrophobic polymer block, and an organic solvent to prepare a w / o / w emulsion; and Stirring the w / o / w emulsion to evaporate the organic solvent to obtain particles having at least the hydrophilic polymer block on the surface.
  • the organic solvent dispersion may further include a hydrophilic active substance, and the particles may include the hydrophilic active substance.
  • the organic solvent dispersion can be emulsified while maintaining the temperature of the aqueous dispersion at 30 ° C. or lower.
  • the aqueous dispersion can be emulsified while maintaining the temperature of the aqueous dispersion at 30 ° C. or lower.
  • the particles have a high structural stability and a small variation in particle diameter.
  • the hydrophilic active substance can be stably included in the inside while maintaining the activity of the hydrophilic active substance, and the hydrophilic The active substance can be released slowly. According to the above method for producing particles, particles having high structural stability and little variation in particle diameter can be produced.
  • FIG. 1 is a diagram schematically illustrating particles according to an embodiment of the present invention, a gel including the particles, and a manufacturing method thereof.
  • FIG. 1 is a diagram schematically illustrating particles according to an embodiment of the present invention, a gel including the particles, and production methods thereof.
  • a particle 10 includes a first layer having an amphiphilic block copolymer 12 including a hydrophilic polymer block and a hydrophobic polymer block, and the first layer.
  • grains 10 can be obtained with the manufacturing method mentioned later.
  • the hydrophobic polymer block is indicated by a solid line and the hydrophilic polymer block is indicated by a shaded line.
  • the particles 10 are, in order from the inside, the hydrophilic polymer block of the first layer (amphiphilic block copolymer 12), the hydrophobic polymer block of the first layer (amphiphilic block copolymer 12), and the second layer ( The hydrophobic polymer block of the amphiphilic block copolymer 12) and the hydrophilic polymer block of the second layer (amphiphilic block copolymer 12) are arranged. Therefore, a hydrophilic polymer block exists on the surface 14 of the particle 10.
  • the presence of the hydrophilic polymer block of the amphiphilic block copolymer 12 on the surface 14 of the particle 10 can be confirmed by measuring the zeta potential on the surface of the particle 10.
  • the hydrophilic polymer block of the amphiphilic block copolymer 12 is present at least on the surface 14 of the particle 10, for example, when the particle 10 is used as a component of the gel 100 for bonding a biological tissue, it exists on the surface 14 of the particle 10. Since the hydrophilic polymer block is bonded to the living tissue, it has excellent adhesion to the living tissue. Further, an aqueous phase or a cavity may exist inside the first layer.
  • the average particle diameter of the particles 10 is usually several tens of nm to several ⁇ m, and preferably 50 nm to 1 ⁇ m.
  • the particles 10 may further include a hydrophilic active substance 16.
  • the hydrophilic active substance 16 can be present inside the first layer (amphiphilic block copolymer 12).
  • the second layer (amphiphilic block copolymer 12) forms a polymer network (not shown), the hydrophilic active substance 16 can be gradually released from the particle 10.
  • the particle 10 according to the present embodiment has high structural stability and little variation in particle diameter.
  • the hydrophilic active material 16 when included, the hydrophilic active material 16 is stabilized in a state where the activity of the hydrophilic active material 16 is maintained. Thus, the hydrophilic active substance 16 can be gradually released.
  • Such particles 10 cannot be obtained by conventional techniques.
  • amphiphilic block copolymer 12 which is a constituent component of the first and second layers is not particularly limited as long as it is an amphiphilic block copolymer having a hydrophobic polymer block and a hydrophilic polymer block. It is preferable that it is a compound represented by 1) or (2).
  • the other end different from the L1 end of ⁇ H.phobic B> in the above general formula (1) has a functional group such as an ethylenically unsaturated group capable of forming a crosslink. May be.
  • an aldehyde group is introduced at the terminal opposite to L1 of the hydrophilic polymer block, as an initiator for producing the amphiphilic block polymer 12, for example, an acetalized formyl (in other words, a protected aldehyde group Compound (for example, using an alcohol (see, for example, WO 96/33233 or the corresponding US Pat. No.
  • Examples of the polymer chain constituting the hydrophilic polymer block having an aldehyde group at the terminal include, for example, poly (ethylene oxide), poly (vinyl alcohol), poly ( Vinylpyrrolidone), poly (N, N-dimethylacrylamide), hydrophilic polyacrylic acid ester, hydrophilic polymethacrylic acid ester, hydrophilic polyacrylic acid amide, hydrophilic polymethacrylic acid amide, polymalic acid, dextran, pullulan, dextran
  • Examples of the polymer chain constituting the hydrophobic polymer block include, for example, poly (D, L-lactic acid), poly (L-lactic acid) , Poly (glycolic acid), poly (D, L-lactic acid-CO-glycolic acid), poly (L-lactic acid-CO-glycolic acid), poly (D, L-lactic acid-CO-glycolic acid) -CO- ⁇ -Caprolactone), poly ( ⁇ -caprolactone), poly ( ⁇ -valerolactone), poly ( ⁇ -butyrolactone), hydrophobic polyester, poly ( ⁇ -benzyl L-aspartate), poly ( ⁇ -substituted aspartate), Poly ( ⁇ -benzyl L-glutamate), poly ( ⁇ -substituted glutamate), poly (phenylalanine), poly (leucine), poly (isoleucine), hydrophobic polyamino acid, poly (propylene) Oxide), poly (te
  • the hydrophobic polymer block can form at least one cross-linking as a side chain at any site in the polymer main chain (preferably the other end different from the side that binds ⁇ H.philic A>). It can have a functional group. These functional groups may be any groups as long as the two functional groups can form a cross-linked bond. For example, ethylenically unsaturated polymerizable groups, mercapto groups, amino groups, hydroxyl groups, carboxyl groups Is preferred.
  • the hydrophobic polymer block preferably has a biodegradable ester bond.
  • the amphiphilic block copolymer 12 can be produced by a known method, and more preferably ⁇ H.philic A> in the general formula (1) or the general formula (2), or the general formula (2).
  • ⁇ H.philic C> contains a poly (ethylene oxide) polymer chain
  • ⁇ H. Phobic B> in the above general formula (1) or (2) contains poly (D, L-lactic acid).
  • amphiphilic block copolymer 12 is particularly preferably represented by the following general formula (IA).
  • the amphiphilic block copolymer is preferably a polyethylene glycol-polylactic acid block copolymer in that the burden on the living body can be reduced.
  • the reactive functional group A is added to the terminal of the hydrophilic polymer block in that the reactivity with the hydrophilic polymer 20 can be enhanced. It is more preferable to have (for example, at least one functional group selected from an aldehyde group, an amino group, a maleimide group, a thiol group, and an N-hydroxysuccinimide ester group).
  • the amphiphilic block copolymer 12 can be used singly or as a mixture of two or more, and contains at least 1% by weight, preferably at least 5% by weight of the amphiphilic block copolymer 12 having an aldehyde group.
  • the weight average molecular weight of the amphiphilic block copolymer 12 is preferably 1,000 to 20,000, and more preferably 3,000 to 10,000.
  • weight average molecular weight is less than 1,000, since the polymer chain is short, it may be difficult to dispose the hydrophilic polymer block on the surface 14 of the particle 10, whereas it exceeds 10,000.
  • amphiphilic block copolymer 12 tends to aggregate, it may be difficult to dispose the hydrophilic polymer block on the surface 14 of the particle 10.
  • the ratio of the number average molecular weight of the hydrophilic polymer block to the number average molecular weight of the hydrophobic polymer block in the amphiphilic block copolymer 12 is preferably 1: 0.01 to 1:10.
  • the hydrophilic polymer block may not be sufficiently oriented on the particle surface.
  • the hydrophilic polymer block of the amphiphilic block copolymer 12 preferably has a reactive functional group.
  • a gel including particles 10 using an amphiphilic block copolymer 12 including a hydrophilic polymer block having a reactive functional group A, and a hydrophilic polymer 20 having a reactive functional group B When used in 100, the reactive functional group A of the hydrophilic polymer block of the amphiphilic block copolymer 12 may react with the reactive functional group B in the hydrophilic polymer 20. In this case, a bond is formed between the hydrophilic polymer block and the hydrophilic polymer 20 to increase the strength of the gel.
  • reactive functional group A and B are not specifically limited, When a gel is used for adhesion
  • the sustained release characteristics are controlled by the diffusion rate of the hydrophilic substances in the water contained in the gel.
  • the sustained release of the hydrophilic active substance 16 is controlled by the particles 10 included in the gel 100.
  • the density of the polymer network mainly composed of the amphiphilic polymer block 12 can be controlled by adjusting the molecular weight of the amphiphilic polymer block 12 constituting the particle 10, hydrophilicity
  • the sustained release rate of the active substance 16 can be precisely controlled.
  • the gel 100 according to the present embodiment since no biological material is used, there is no risk of infection, and there is no possibility of generating a highly toxic byproduct, so that the safety is high.
  • the particle 10 according to this embodiment may include a hydrophilic active substance 16. Since the particle
  • hydrophilic active substance 16 examples include hydrophobic proteins, genes, and low molecular compounds.
  • a particle manufacturing method includes an amphiphilic block copolymer 12 including a hydrophilic polymer block and a hydrophobic polymer block, and water 19 as shown in FIG.
  • emulsifying the aqueous dispersion containing the aqueous dispersion to prepare a w / o / w emulsion 13 and evaporating the organic solvent 18 by stirring the w / o / w emulsion 13 so that the hydrophilic polymer block is at least A step of obtaining particles 10 present on the surface.
  • the organic solvent dispersion includes the hydrophilic active substance 16
  • the aqueous phase 19 in the obtained o / w emulsion 11 contains the hydrophilic active substance 16.
  • the amphiphilic block copolymer 12 is disposed so as to surround the organic solvent 18 in the o / w emulsion 11.
  • the amphiphilic block copolymer 12 is disposed such that the hydrophobic polymer block is located on the inner side and the hydrophilic polymer block is located on the outer side.
  • the organic solvent 18 any organic solvent that is miscible or immiscible with water can be used, but an organic solvent that exhibits a property immiscible with water is more preferable.
  • the property of being immiscible with water means that it is separated into two phases when the same volume of water and an organic solvent are mixed.
  • the organic solvent 18 preferably has a boiling point lower than that of water in that the organic solvent 18 can be efficiently removed in the stirring step described later.
  • the organic solvent 18 is not particularly limited as long as the amphiphilic block copolymer 12 can be dissolved.
  • hydrocarbon solvents such as n-hexane, toluene and xylene, and halogen hydrocarbon solvents such as dichloromethane and chloroform.
  • ester solvents such as ethyl acetate and ether solvents such as diethyl ether.
  • the amount of the organic solvent 18 used relative to the amount of water 19 used is preferably 1/10 to 1/2, and the amount of the amphiphilic block copolymer 12 used relative to the amount of organic solvent 18 used is It is preferably 0.005 g / ml to 2 g / ml.
  • emulsifying means for example, general emulsifying means such as high-speed stirring, ultrasonic irradiation, and membrane emulsification can be used. Moreover, you may emulsify by adding a suitable dispersion stabilizer (for example, polyvinyl alcohol, polyethyleneglycol etc.) to an aqueous dispersion.
  • a suitable dispersion stabilizer for example, polyvinyl alcohol, polyethyleneglycol etc.
  • the emulsification is preferably carried out while maintaining the temperature of the aqueous dispersion at 30 ° C. or lower, for example, 10 to 20 ° C. is more preferable.
  • the emulsification is carried out in a state where the temperature of the aqueous dispersion exceeds 30 ° C., the evaporation rate of the organic solvent 18 becomes too fast, so that the resulting particles 10 are likely to be deformed and the amphiphilic block copolymer 12. As a result of increasing the mobility of the particles, aggregation of the particles 10 may easily occur.
  • an aqueous dispersion further containing the hydrophilic active substance 16 is emulsified.
  • the hydrophilic active substance 16 can be contained in the organic solvent 18 of the o / w emulsion 11 as shown in the upper central view of FIG.
  • the sustained release particles 10 further containing the hydrophilic active substance 16 inside the particles 10 (mainly in the hydrophilic polymer block of the first layer) are provided. Obtainable.
  • the particle diameter of the obtained particles 10 can be controlled by controlling the speed at the time of stirring the w / o / w emulsion 13. That is, according to the manufacturing method according to the present embodiment, the particles 10 having the same particle diameter and shape can be obtained by a simple method.
  • the particles 10 according to this embodiment can be expected to be used as various medical tools such as therapeutic drugs, diagnostic drugs, therapeutic devices, and measurement devices.
  • particles 10 having PEG introduced on the surface as a hydrophilic polymer block can suppress adsorption of blood cell components such as platelets and leukocytes, and can be used as an antithrombotic material.
  • the particles 10 according to the present embodiment can be used as, for example, a drug holding carrier, a functional contrast agent, an indwelling drug sustained release material, and the like.
  • a fluorescent substance as the hydrophilic active substance 16 in the particle 10 according to the present embodiment, it can be used as a bioimaging reagent not only in the medical field but also in the biochemical field.
  • the particles 10 according to the present embodiment have wide applicability mainly in the fields of medicine, pharmacy, and biochemistry.
  • the gel 100 may include particles 10 and a hydrophilic polymer 20.
  • the bonding mode between the particles 10 and the hydrophilic polymer 20 is not particularly limited, and may be, for example, physical adsorption or chemical bonding. However, sufficient gel strength can be obtained, and binding ability to living tissue can be obtained. To increase it, chemical bonds are preferred.
  • the particle 10 can have a reactive functional group A
  • the hydrophilic polymer 20 can have a reactive functional group B.
  • the reactive functional group A or B is a functional group that binds to an amino group abundantly present on the surface of a living tissue, a gel 100 having strong tissue adhesion can be obtained.
  • Gel 100 can be suitably used for adhesion to living tissue, for example. More specifically, the gel 100 can be used as a hydrogel.
  • the gel 100 can be used as a hydrogel for a wide range of medical applications such as soft contact lenses, artificial muscles, artificial breasts, artificial skin, wound healing materials, and drug-encapsulating carriers in drug delivery systems.
  • the gel 100 using the particles 10 encapsulating a substance having a hemostatic action as the hydrophilic active substance 16 can be used as a hemostatic material.
  • the gel 100 can be used as an anti-adhesion material in the peritoneum after surgery such as the ovary or an embolization material for intravascular surgery by utilizing the property that the gel 100 adheres to the tissue.
  • the resulting amphiphilic block copolymer was reprecipitated in 2-propanol and then lyophilized with benzene.
  • the results of calculating the molecular weight of the amphiphilic block copolymer by gel filtration chromatography (GPC) and 1 H-NMR measurement are shown below.
  • This w / o emulsion solution is then mixed with an organic solvent (2 ml) containing an amphiphilic block copolymer (Acetal-PEG-PLA) and dialyzed against water overnight to produce a hydrophilic polymer block (PEG ) And Acetal-PEG-PLA particles having a water phase in the interior (core) were prepared.
  • an organic solvent (2 ml) containing an amphiphilic block copolymer (Acetal-PEG-PLA) and dialyzed against water overnight to produce a hydrophilic polymer block (PEG )
  • Acetal-PEG-PLA particles having a water phase in the interior (core) were prepared.
  • This w / o emulsion solution is then mixed with an organic solvent (2 ml) containing an amphiphilic block copolymer (Acetal-PEG-PLA) and dialyzed against water overnight to produce a hydrophilic polymer block (PEG ) And Acetal-PEG-PLA particles having a water phase in the interior (core) were prepared.
  • an organic solvent (2 ml) containing an amphiphilic block copolymer (Acetal-PEG-PLA) and dialyzed against water overnight to produce a hydrophilic polymer block (PEG )
  • Acetal-PEG-PLA particles having a water phase in the interior (core) were prepared.
  • Example 5 (Preparation of particles) The resulting amphiphilic block copolymer (Acetal-PEG-PLA) (0.5 g) was dissolved in acetonitrile (4 ml), and an aqueous phase (1%) containing 2 w / v% polyvinyl alcohol (PVA) (0.02 g) ml) to prepare a w / o emulsion.
  • Acetal-PEG-PLA 0.5 g
  • PVA polyvinyl alcohol
  • This w / o emulsion solution is then mixed with an organic solvent (2 ml) containing an amphiphilic block copolymer (Acetal-PEG-PLA) and dialyzed against water overnight to produce a hydrophilic polymer block (PEG ) And Acetal-PEG-PLA particles having a water phase in the interior (core) were prepared.
  • an organic solvent (2 ml) containing an amphiphilic block copolymer (Acetal-PEG-PLA) and dialyzed against water overnight to produce a hydrophilic polymer block (PEG )
  • Acetal-PEG-PLA particles having a water phase in the interior (core) were prepared.
  • the obtained gel was put into a dialysis membrane (material: regenerated cellulose) and dialyzed against water to evaluate the sustained release characteristics of ⁇ -chymotrypsin. As a result, it took 120 hours for sustained release of 50 w / w% ⁇ -chymotrypsin. That is, it succeeded in sustained release of the hydrophilic active substance, which was impossible with conventional gels.
  • the present invention is not limited to the above-described embodiments, and various modifications can be made.
  • the present invention also includes configurations that are substantially the same as the configurations described in the embodiments (for example, configurations that have the same functions, methods, and results, or configurations that have the same purposes and results).
  • the invention includes a configuration in which a non-essential part of the configuration described in the embodiment is replaced.
  • the present invention includes a configuration that achieves the same effect as the configuration described in the embodiment or a configuration that can achieve the same object.
  • the invention includes a configuration in which a known technique is added to the configuration described in the embodiment.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Cette invention concerne : des particules qui : présentent une stabilité structurelle élevée et de faibles variations sous l’angle de la taille, peuvent renfermer une substance à activité hydrophile ou analogue de manière stable tout en maintenant l’activité de cette substance hydrophile ou analogue, et peuvent libérer ladite substance hydrophile d’une manière soutenue ; un procédé d’obtention desdits particules ; et un gel. Chacune des particules comprend une première couche et une seconde couche disposée à l’extérieur de la première couche. Dans chacune de ces particules, les première et seconde couches comprennent un copolymère bloc amphiphile constitué d’un bloc polymère hydrophile et d’un bloc polymère hydrophobe. Dans la première couche, le bloc polymère hydrophile est disposé à l’intérieur, et le bloc polymère hydrophobe à l’extérieur. Dans la seconde couche, le bloc polymère hydrophobe est disposé à l’intérieur, et le bloc polymère hydrophile à l’extérieur
PCT/JP2009/004421 2008-09-08 2009-09-07 Particules, leur procédé de fabrication, et gels WO2010026781A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2008-229700 2008-09-08
JP2008229700A JP2010064956A (ja) 2008-09-08 2008-09-08 粒子およびその製造方法、ならびにゲル

Publications (1)

Publication Number Publication Date
WO2010026781A1 true WO2010026781A1 (fr) 2010-03-11

Family

ID=41796958

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2009/004421 WO2010026781A1 (fr) 2008-09-08 2009-09-07 Particules, leur procédé de fabrication, et gels

Country Status (2)

Country Link
JP (1) JP2010064956A (fr)
WO (1) WO2010026781A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016530035A (ja) * 2013-09-10 2016-09-29 エスプシ パリテク 生体接着に使用するためのナノ粒子
JP2016539699A (ja) * 2013-12-10 2016-12-22 インサーム（インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル）Ｉｎｓｅｒｍ（Ｉｎｓｔｉｔｕｔ Ｎａｔｉｏｎａｌ Ｄｅｌａ Ｓａｎｔｅ Ｅｔ Ｄｅ Ｌａ Ｒｅｃｈｅｒｃｈｅ Ｍｅｄｉｃａｌｅ） 組織表面及び材料を接着する方法、並びにその生物医学的使用
CN111035794A (zh) * 2019-12-23 2020-04-21 宁波宝亭生物科技有限公司 一种可吸收多孔微球止血粉的制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102144479B1 (ko) * 2018-05-24 2020-08-13 주식회사 덱스레보 조직 수복용 조성물 및 이의 제조방법

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000501084A (ja) * 1995-11-24 2000-02-02 シェリング アクチェンゲゼルシャフト 均一な形態を有するマイクロカプセルの製造方法、並びにこの方法により製造されたマイクロカプセル
US20050003016A1 (en) * 1999-12-14 2005-01-06 Discher Dennis E. Controlled release polymersomes
JP2007500192A (ja) * 2003-07-25 2007-01-11 ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア 高度放射性プローブを組合わせたポリマーソーム
JP2007023023A (ja) * 2005-06-15 2007-02-01 Kanagawa Acad Of Sci & Technol 組織接着性薬剤放出ゲル形成用組成物
WO2007038763A1 (fr) * 2005-09-28 2007-04-05 The Trustees Of The University Of Pennsylvania Polymersomes biodegradables autoassembles
JP2008535644A (ja) * 2005-03-04 2008-09-04 プレジデント・アンド・フエローズ・オブ・ハーバード・カレツジ 多重エマルジョンの形成のための方法および装置

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000501084A (ja) * 1995-11-24 2000-02-02 シェリング アクチェンゲゼルシャフト 均一な形態を有するマイクロカプセルの製造方法、並びにこの方法により製造されたマイクロカプセル
US20050003016A1 (en) * 1999-12-14 2005-01-06 Discher Dennis E. Controlled release polymersomes
JP2007500192A (ja) * 2003-07-25 2007-01-11 ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア 高度放射性プローブを組合わせたポリマーソーム
JP2008535644A (ja) * 2005-03-04 2008-09-04 プレジデント・アンド・フエローズ・オブ・ハーバード・カレツジ 多重エマルジョンの形成のための方法および装置
JP2007023023A (ja) * 2005-06-15 2007-02-01 Kanagawa Acad Of Sci & Technol 組織接着性薬剤放出ゲル形成用組成物
WO2007038763A1 (fr) * 2005-09-28 2007-04-05 The Trustees Of The University Of Pennsylvania Polymersomes biodegradables autoassembles

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MENG, F. ET AL.: "Biodegradable polemersomes", MACROMOLECULES, vol. 36, no. 9, 2003, pages 3004 - 3005 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016530035A (ja) * 2013-09-10 2016-09-29 エスプシ パリテク 生体接着に使用するためのナノ粒子
JP2016539699A (ja) * 2013-12-10 2016-12-22 インサーム（インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル）Ｉｎｓｅｒｍ（Ｉｎｓｔｉｔｕｔ Ｎａｔｉｏｎａｌ Ｄｅｌａ Ｓａｎｔｅ Ｅｔ Ｄｅ Ｌａ Ｒｅｃｈｅｒｃｈｅ Ｍｅｄｉｃａｌｅ） 組織表面及び材料を接着する方法、並びにその生物医学的使用
CN111035794A (zh) * 2019-12-23 2020-04-21 宁波宝亭生物科技有限公司 一种可吸收多孔微球止血粉的制备方法
CN111035794B (zh) * 2019-12-23 2023-11-14 宁波宝亭生物科技有限公司 一种可吸收多孔微球止血粉的制备方法

Also Published As

Publication number Publication date
JP2010064956A (ja) 2010-03-25

Similar Documents

Publication Publication Date Title
Fan et al. Recent development of unimolecular micelles as functional materials and applications
Sayed et al. Porous inorganic drug delivery systems—a review
Nishiyama et al. Nanostructured devices based on block copolymer assemblies for drug delivery: designing structures for enhanced drug function
Bromberg et al. Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery
JP4339595B2 (ja) 有効成分を送達するための両親媒性共重合体をベースとするナノ粒子コロイド懸濁液
Kang et al. Tailoring the stealth properties of biocompatible polysaccharide nanocontainers
JP6092121B2 (ja) 疎水性分子に誘起された分岐ポリマー凝集体及びその使用
US20020041898A1 (en) Novel targeted delivery systems for bioactive agents
JP2003503522A (ja) 分解性架橋剤およびこれを用いて形成される架橋網目構造ポリマー
WO2008157422A1 (fr) Matériaux, procédés et systèmes pour administration de médicament par ultrasons facilitée par cavitation
JPH11510837A (ja) 薬物送達のための制御された放出薬剤および組織処置薬剤としての使用のためのマルチブロック生分解性ヒドロゲル
TW200902097A (en) Method of formation of viscous, shape conforming gels and their uses as medical prosthesis
WO2005007136A1 (fr) Procedes de fabrication de formulations pharmaceutiques destinees a la delivrance de medicaments possedant une faible solubilite aqueuse
Mariyam et al. Dendrimers: general aspects, applications and structural exploitations as prodrug/drug-delivery vehicles in current medicine
Patel et al. Synthetic strategy of dendrimers: A review
CN101186706B (zh) 一种peg系凝胶纳米颗粒的制备方法
WO2006107311A2 (fr) Vesicules polymeres biocompatible auto-assemblees a partir de copolymeres trisequences
CN105518031A (zh) 用于制备隐形纳米颗粒的方法
Daubian et al. One-pot synthesis of an amphiphilic ABC triblock copolymer PEO-b-PEHOx-b-PEtOz and its self-assembly into nanoscopic asymmetric polymersomes
WO2010026781A1 (fr) Particules, leur procédé de fabrication, et gels
JP4262090B2 (ja) 自己凝集体を形成する抗癌剤−キトサン複合体及びその製造方法
US20120269895A1 (en) Dendritic pic micelles with bioactive proteins
JP2010065067A (ja) 粒子およびその製造方法、ならびにゲル
JP5201763B2 (ja) 異なる平均粒径サイズの粒子からなる混合微粒子カプセルの製造方法
CN105213307B (zh) 用于粘液渗透的还原响应性靶向高分子胶束及其制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09811311

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09811311

Country of ref document: EP

Kind code of ref document: A1