[go: up one dir, main page]

WO2018190688A1 - Granules composites organiques et inorganiques et leur procédé de production - Google Patents

Granules composites organiques et inorganiques et leur procédé de production Download PDF

Info

Publication number
WO2018190688A1
WO2018190688A1 PCT/KR2018/004363 KR2018004363W WO2018190688A1 WO 2018190688 A1 WO2018190688 A1 WO 2018190688A1 KR 2018004363 W KR2018004363 W KR 2018004363W WO 2018190688 A1 WO2018190688 A1 WO 2018190688A1
Authority
WO
WIPO (PCT)
Prior art keywords
organic
inorganic
granules
inorganic composite
solution
Prior art date
Application number
PCT/KR2018/004363
Other languages
English (en)
Korean (ko)
Inventor
윤희숙
박홍현
Original Assignee
한국기계연구원
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 한국기계연구원 filed Critical 한국기계연구원
Publication of WO2018190688A1 publication Critical patent/WO2018190688A1/fr
Priority to US16/598,299 priority Critical patent/US11801222B2/en

Links

Images

Classifications

    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/20—Polysaccharides
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/12—Powdering or granulating
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/12—Powdering or granulating
    • C08J3/122—Pulverisation by spraying
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2207/00—Foams characterised by their intended use
    • C08J2207/10—Medical applications, e.g. biocompatible scaffolds

Definitions

  • Bioceramic which is representative of calcium phosphate, is a bioceramic alone or a ceramic-biopolymer organic-inorganic composite, and is used as a bone graft material or a bone filler in various forms such as powder, granule, paste, and support.
  • granular form since it can be easily applied to the irregular defects alone or in the form of paste, it has been variously applied in the fields of dentistry and orthopedics.
  • it is also used to adsorb various drugs to ceramic or organic-inorganic composite granules.
  • Spray drying method has the advantage of producing a large amount of granules in a short time, but has a disadvantage in that the production yield in the required size is very low due to the large size distribution of the granules.
  • the chemical reaction method has the advantage of producing a relatively uniform size granules, but the mass production is difficult and the manufacturing process has a disadvantage.
  • Korean Laid-Open Patent Publication No. 10-2010-0026910 adds calcium phosphate microspheres carrying alendronate, a osteoporosis treatment, to bone fractures caused by osteoporosis. Filling materials are disclosed. However, this is difficult to mass production in a short time by obtaining a microsphere through the sol-gel process, there is a disadvantage that the size control of the produced microsphere is not easy.
  • Korean Patent Publication No. 10-2012-0021899 discloses a method for preparing a porous organic-inorganic hybrid, specifically, a crystal comprising a step of supporting an ionic compound or a polar compound on the porous organic-inorganic hybrid.
  • a method for producing a porous, organic-inorganic hybrid cannot obtain granules having a uniform particle size, and there is a problem in mass production of granules.
  • Electrostatic spraying is a method of atomizing a liquid by an electric force (electric field).
  • Liquid droplets formed by electrospray have attracted attention as a useful nanotechnology in recent years because they have a high chargeability and have the advantage of preventing aggregation by their own dispersion.
  • the electrospray technology is expected to be applied in a variety of fields because it is possible to deposit a fine and complex structure with low-cost equipment and easy operation in the air environment.
  • the microspray coater may be exemplified as the electrospray apparatus using the electrostatic charge method.
  • Microgranular coating machine is mainly applied to organic matter. That is, it is used in the fields of pharmaceuticals, chemistry, cosmetics, foodstuffs, agriculture, etc. for the purpose of delivering active ingredients by forming granules using polymers and hydrogels and forming core-shell granules containing oils and various drugs therein. It is becoming.
  • by providing an encapsulated microgranular coating machine has been applied to the food industry by realizing the effects of aging, storage stability, blocking harmful substances.
  • it is being applied to the pharmaceutical industry by realizing effects such as release control, solubility and osmoticity improvement.
  • a raw material may have a high viscosity, or in the case of a material having good aggregation, problems such as clogging of the nozzle may occur.
  • the inventors of the present invention can produce granules of uniform size in a short time and have high content of an inorganic member (for example, a ceramic member), which is highly applicable to bone graft materials and bone fillers, and a method for preparing organic-inorganic composite granules.
  • an inorganic member for example, a ceramic member
  • the present invention was completed by studying.
  • the present invention includes an organic member and an inorganic member, the weight ratio of the inorganic member to the organic member is 1 to 10, the size is 100 to 2000 ⁇ m, and the distribution range of the size is -20% to +20 relative to the size of the granules. It provides the organic-inorganic complex granules, characterized in that the range of%, hydrogel phase.
  • the present invention comprises the steps of preparing an organic member solution; Uniformly dispersing an inorganic member having a weight ratio of 1 to 10 with respect to the organic member in the organic member solution to form an organic-inorganic composite solution; Spraying the organic-inorganic composite solution in an electrostatic charge manner; It provides a method for producing an organic-inorganic composite granules comprising a; and forming a hydrogel phase by polymerizing the sprayed organic-inorganic composite solution.
  • the organic-inorganic composite granules of the present invention have an effect of having a uniform size, and also have an effect of sustained release when supporting a functional member. In addition, there is an advantage of easy cell culture. Furthermore, the production method of the present invention can produce a large amount of organic-inorganic composite granules of uniform size in a short time, there is an advantage that can be produced in a high yield granules. Therefore, the organic-inorganic composite granules and the manufacturing method thereof according to the present invention has an advantage that can be applied to various fields, such as pharmaceutical, medical, cosmetics, food.
  • FIG. 1 is a view showing a photograph and the size and size distribution of the composite granules prepared by the embodiments of the present invention
  • the organic member included in the raw material used in the production method of the present invention has a high viscosity and the inorganic member has a very high cohesiveness, it is generally not suitable for making granules by an electrostatic charge method.
  • the granules can be prepared in an electrostatic manner by adding a step of uniformly dispersing the inorganic member in the member solution, and further, if necessary, further dispersing the inorganic member with a post-coagulation mixer and stirring with an ultrasonic mixer.
  • the size of the spray nozzle of the microgranular coater is preferably 50 ⁇ m to 1000 ⁇ m.
  • the size is less than 50 ⁇ m, it is difficult to spray the organic-inorganic composite solution including the inorganic member through the nozzle due to nozzle clogging, etc., and when the size is more than 1000 ⁇ m, the size is easily applicable to the current clinical practice. There is a problem that the production of micro-sized particles is difficult.
  • the voltage is preferably 500V to 2,500V. If the voltage is less than 500 V, uniform spraying of the sprayed solution is difficult, making it difficult to form spherical particles.
  • a dispersing agent for the dispersion of an inorganic member.
  • dispersants are used for uniform dispersion due to the cohesiveness of the inorganic member. If the dispersant is included in the granules to be produced, problems may arise, for example, in the medical, pharmaceutical, food, and cosmetic fields. Therefore, in the production method of the present invention, there is an advantage that can greatly extend the field of application of the granules to be produced, without using a dispersant.
  • stirring and dispersion are performed through a co-rotating mixer or an ultrasonic mixer.
  • the production method of the present invention in the preparation of organic-inorganic composite granules having sustained release and cell transferability, by producing the granules by the electrostatic charge method, the yield is improved, and the advantage of producing a large amount of granules in a short time have.
  • it is possible to produce a granule of uniform size has the advantage that it is easy to apply to various fields.
  • the functional member or the cell can be easily supported, there is no need to use an organic solvent or dispersant in the manufacturing process, there is an advantage that can be greatly extended to the field of application, such as medical, pharmaceutical, food, cosmetics .
  • Dispersibility increased significantly with the mixing time, but after 30 minutes of ultrasonic mixer treatment, the temperature in solution reached about 40 °C, which was high for delivering bioactive substances such as cells and proteins after treatment. May be a constraint, the treatment time of the ultrasonic mixer was limited to 30 minutes.
  • Paste mixer was used as co-rotation mixer
  • Rotational sonicator was used as ultrasonic mixer, and each was performed for 6 minutes and 15 minutes.
  • An organic-inorganic composite granule on a hydrogel was prepared in the same manner as in Example 1, except that quercetin, which is a functional member, was mixed with the organic-inorganic composite solution in an amount of 1 wt% based on the weight of the organic-inorganic composite solution.
  • the organic-inorganic composite granules on the hydrogel were prepared in the same manner as in Example 1 except that the quoscetin, which is a functional member, was mixed with the organic-inorganic composite solution in an amount of 2.5 wt% based on the weight of the organic-inorganic composite solution.
  • the organic-inorganic composite granules on the hydrogel were prepared in the same manner as in Example 1, except that quercetin, which is a functional member, was mixed with the organic-inorganic composite solution in an amount of 5 wt% based on the weight of the organic-inorganic composite solution.
  • Alginate an organic member
  • a nano-apatite which is an inorganic member
  • a co-rotating mixer and an ultrasonic mixer were used at a weight ratio of 1: 4 (organic member: inorganic member) at a weight ratio of the organic member, using a co-rotating mixer and an ultrasonic mixer. And mixed to prepare an organic-inorganic complex solution.
  • Paste mixer was used as co-rotation mixer
  • Rotational sonicator was used as ultrasonic mixer, and each was performed for 6 minutes and 15 minutes.
  • the organic-inorganic composite solution prepared above was introduced into a microgranular coating machine (Buchi, B-395 pro), sprayed with a nozzle having a diameter of 150 ⁇ m, and dropped into a CaCl 2 solution to prepare organic-inorganic composite granules on a hydrogel. . After dropping, the mixture was crosslinked in CaCl 2 solution for 30 minutes, and then washed twice with PBS. In order to measure the size, a certain amount of organic / inorganic composite granules were transferred to a petri dish to obtain an image through an optical microscope, and the size of the particles was calculated using an ImageJ program to calculate the average size of the particles.
  • Organic member An organic-inorganic composite granule was prepared in the same manner as in Example 5 except that the inorganic member was 1: 6.
  • Organic member An organic-inorganic composite granule was prepared in the same manner as in Example 5 except that the inorganic member was 1: 8.
  • Organic member An organic-inorganic composite granule was prepared in the same manner as in Example 5 except that the inorganic member was 1:10.
  • Organic-inorganic composite granules were prepared in the same manner as in Examples 5 to 8 except that a nozzle having a diameter of 200 ⁇ m was used.
  • the organic-inorganic composite granules prepared in Examples 1 to 4 were confirmed the form of the granules through an optical microscope, and the size and distribution of the size were confirmed using ImageJ software, and the results are shown in FIG. 1.
  • the organic-inorganic composite granules according to the present invention are spherical, having a size range of about 250 to about 270 ⁇ m, and having a uniform size that does not deviate from ⁇ 20%.
  • Organic member Inorganic member Theoretical weight ratio Actual weight ratio 1: 0.1 0.1 0.124 1: 0.25 0.25 0.271 1: 1 One 0.962 1: 2.5 2.5 2.796 1:10 10 7.760
  • the inorganic member content of the actually prepared organic-inorganic composite granules is almost equal to the amount of the inorganic member introduced into the raw material, and thus, no precipitation or clogging of the inorganic member occurs in the manufacturing process, and thus a high yield. It can be seen that the composite granules can be prepared.
  • the organic-inorganic complex granules prepared in Examples 1 to 4 were placed in a phosphate buffer solution (PBS), and the PBS solution was taken using the total substitution method for each time, and then the concentration of the drug was released by measuring the absorbance using the spectroscopic analysis method. The release behavior was confirmed by calculating.
  • PBS phosphate buffer solution
  • the organic-inorganic complex granules prepared in Examples 1 to 4 were placed on the transwell, and the cells were attached to the well plate surface, and then cultured together in the culture medium.
  • the quercetin-sensing organic-inorganic complex granules were removed, and the culture solution was also removed. After washing with PBS, the culture solution containing the MTS assay was applied and then left in a cell culture incubator for 2 hours. The cultures were then taken and measured for absorbance at 495 nm using a plater reader to analyze cell proliferation trends.
  • the drug is gradually released over time
  • the degree of cell proliferation is increased by the released drug.
  • the organic-inorganic complex granules of the present invention can be used for drug delivery, and specifically, for example, it can be seen that it can be used for treating osteoporosis and the like in the body.
  • the degree of cell proliferation in the first week is almost the same, but in the second week through the fact that the cell proliferation occurs more if the quercetin content, the sustained-release characteristics of the organic-inorganic complex granules according to the present invention You can check it.
  • osteoblasts (MC3T3) is introduced into the complex solution at a concentration of 1.0 X 106 cells / ml and 5.0 X 106 cells / ml, and then slowly Stirred. Thereafter, the method was sprayed in the same manner as described in Example 5, and this was added dropwise to a CaCl 2 solution to prepare an organic-inorganic composite granule on a hydrogel. Thereafter, in order to confirm whether the cells were supported in the composite granules, staining was performed using a DAPI solution capable of discriminating cell nuclei, and confirmed through a fluorescence microscope, which is shown in FIG. 4. According to Figure 4, it can be seen that cells are uniformly supported in the organic-inorganic complex granules of the present invention.
  • Inorganic-inorganic composite solution was prepared by the same method as described in Example 5.
  • the prepared organic-inorganic composite solution was mixed for 6 minutes using a magnetic stirrer and 21 minutes of mixing.
  • the prepared organic-inorganic composite solution was mixed for 6 minutes with a co-rotating mixer, followed by an ultrasonic mixer for 15 minutes. Agitation was carried out, and then stained using an Alizarin red solution, and the result was confirmed through an optical microscope.
  • FIG. 5A it can be seen that when the stirring is performed with a general magnetic stirrer, the organic member and the inorganic member are not sufficiently mixed, and the inorganic members are heavily aggregated with each other.
  • the organic-inorganic composite granules prepared in Examples 5 to 16 were confirmed the form of the granules through an optical microscope, and the size and distribution of size were confirmed using ImageJ software, and the results are shown in FIG. 6.
  • the organic-inorganic composite granules according to the present invention have a spherical shape, have a size range of about 200 to about 500 ⁇ m, and the size distribution has a uniform size that does not deviate from ⁇ 15%.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Composite Materials (AREA)
  • Biochemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'objectif de la présente invention est de fournir des granules composites organiques et inorganiques d'une taille uniforme et un procédé de production de celles-ci. À cet effet, la présente invention concerne des granules composites inorganiques et organiques qui sont sous forme d'hydrogel et comprennent des composants organiques et des composants inorganiques, le rapport en poids des éléments inorganiques aux éléments organiques étant de 1 à 10, les tailles des composants organiques et des composants inorganiques sont de 100 à 2 000 μm, et la distribution de taille est de -20 % à +20 % par rapport à la taille des granules. La présente invention concerne en outre un procédé de production de granules composites organiques et inorganiques. Les granules composites organiques et inorganiques de la présente invention ont l'effet d'avoir une taille uniforme, et ont en outre l'effet d'une libération prolongée lorsqu'un composant fonctionnel est contenu. En outre, il existe un avantage en ce que la culture de cellules est facile. En outre, le procédé de production de la présente invention présente des avantages en ce qu'un grand nombre de granules composites organiques et inorganiques d'une taille uniforme peuvent être produits en un temps court, et les granules peuvent être produits avec un rendement élevé. Par conséquent, les granules composites organiques et inorganiques et le procédé de production de ceux-ci selon la présente invention peuvent être appliqués à différents domaines tels que le domaine pharmaceutique, le domaine médical, le domaine cosmétique, le domaine alimentaire, etc.
PCT/KR2018/004363 2017-04-14 2018-04-13 Granules composites organiques et inorganiques et leur procédé de production WO2018190688A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US16/598,299 US11801222B2 (en) 2017-04-14 2019-10-10 Manufacturing method for granule

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2017-0048463 2017-04-14
KR20170048463 2017-04-14

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2018/004362 Continuation-In-Part WO2018190687A1 (fr) 2017-04-14 2018-04-13 Procédé de fabrication de granulés céramiques sphériques

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US16/598,299 Continuation-In-Part US11801222B2 (en) 2017-04-14 2019-10-10 Manufacturing method for granule

Publications (1)

Publication Number Publication Date
WO2018190688A1 true WO2018190688A1 (fr) 2018-10-18

Family

ID=63793578

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2018/004363 WO2018190688A1 (fr) 2017-04-14 2018-04-13 Granules composites organiques et inorganiques et leur procédé de production

Country Status (2)

Country Link
KR (1) KR102227720B1 (fr)
WO (1) WO2018190688A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5639467A (en) * 1992-05-29 1997-06-17 The Regents Of The University Of California Electrostatic process for manufacturing coated transplants and product
US20050170012A1 (en) * 2001-03-02 2005-08-04 Stryker Corporation Porous beta-tricalcium phosphate granules for regeneration of bone tissue
KR20140007546A (ko) * 2012-07-09 2014-01-20 주식회사 메가젠임플란트 인산칼슘계 다공성 골 대체재의 제조 방법 및 이에 의하여 제조된 인산칼슘계 다공성 골 대체재
KR20160122657A (ko) * 2015-04-13 2016-10-24 서울대학교산학협력단 이중가교된 생분해성 고분자 하이드로겔-인산칼슘 복합체 및 이의 제조방법

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101115964B1 (ko) 2008-08-29 2012-02-21 한스바이오메드 주식회사 서방형 골다공증치료제를 담지한 골충진재
KR101178204B1 (ko) * 2009-06-24 2012-08-30 단국대학교 산학협력단 다공성 마이크로스피어 및 이의 제조방법
CN101991593A (zh) 2009-08-14 2011-03-30 张景元 槲皮苷在制药中的应用
KR20120021899A (ko) 2010-08-20 2012-03-09 한국화학연구원 다공성 유무기 혼성체, 그의 제조 방법, 그를 포함하는 흡착제 및 그의 응용
KR101299629B1 (ko) * 2011-04-12 2013-08-23 주식회사 바이오알파 성장인자 단백질을 담지한 마이크로스피어-하이드로겔 복합체의 제조방법
KR101647183B1 (ko) * 2014-03-04 2016-08-11 단국대학교 천안캠퍼스 산학협력단 치료약물 및 세포전달용 마이크로입자 및 이의 제조방법
KR101892731B1 (ko) 2017-08-07 2018-08-29 한국기계연구원 구형 세라믹 과립 및 이의 제조방법

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5639467A (en) * 1992-05-29 1997-06-17 The Regents Of The University Of California Electrostatic process for manufacturing coated transplants and product
US20050170012A1 (en) * 2001-03-02 2005-08-04 Stryker Corporation Porous beta-tricalcium phosphate granules for regeneration of bone tissue
KR20140007546A (ko) * 2012-07-09 2014-01-20 주식회사 메가젠임플란트 인산칼슘계 다공성 골 대체재의 제조 방법 및 이에 의하여 제조된 인산칼슘계 다공성 골 대체재
KR20160122657A (ko) * 2015-04-13 2016-10-24 서울대학교산학협력단 이중가교된 생분해성 고분자 하이드로겔-인산칼슘 복합체 및 이의 제조방법

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NEMETHOV A ET AL.: "Vibration technology for microencapsulation: the restrictive role of viscosity", BIOPROCESSING & BIOTECHNIQUES, vol. 5, no. 1, 1 May 2015 (2015-05-01), pages 199 - 201, XP055559413, Retrieved from the Internet <URL:doi:10.4172/2155-9821.1000199> *

Also Published As

Publication number Publication date
KR102227720B1 (ko) 2021-03-16
KR20180116162A (ko) 2018-10-24

Similar Documents

Publication Publication Date Title
Lin et al. Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration
EP3313944A1 (fr) Bio-encre à deux constituants, biomatériau 3d la comprenant et son procédé de préparation
Gentile et al. Composite scaffolds for controlled drug release: Role of the polyurethane nanoparticles on the physical properties and cell behaviour
Lee et al. A biomimetic macroporous hybrid scaffold with sustained drug delivery for enhanced bone regeneration
Kim et al. Microspheres of collagen-apatite nanocomposites with osteogenic potential for tissue engineering
US9889234B2 (en) Scaffold for hard tissue regeneration containing active ingredient for treating osteoporosis and preparing method thereof
EP0314109A2 (fr) Composition biorésorbable de collagène pour le traitement de blessures sur la peau
WO2018030612A1 (fr) Microsphère polymère poreuse pour la prévention ou le traitement de maladies des tissus mous et son procédé de préparation
WO2016032197A1 (fr) Matériau de greffe osseuse ayant une protéine morphogénétique enrobée et une matrice extracellulaire, et procédé de préparation
WO2014092239A1 (fr) Produit d&#39;étanchéité de tissu, dans lequel sont mélangés du collagène et de la fibrine, et son procédé de préparation
WO2022124508A1 (fr) Composition injectable pour réparation tissulaire et son procédé de préparation
WO2016043547A1 (fr) Composition pour réparation tissulaire et son procédé de préparation
US20100143439A1 (en) Hybrid Biomimetic Particles, Methods of Making Same and Uses Therefor
Gaihre et al. Thermoresponsive injectable microparticle–gel composites with recombinant BMP-9 and VEGF enhance bone formation in rats
WO2022050694A1 (fr) Patch d&#39;hydrogel biomimétique adhérant au tissu pour la prévention ou le traitement de maladies du cartilage ou des os
WO2018190687A1 (fr) Procédé de fabrication de granulés céramiques sphériques
WO2018190688A1 (fr) Granules composites organiques et inorganiques et leur procédé de production
Qin et al. Construction of a BMP‐2 gene delivery system for polyetheretherketone bone implant material and its effect on bone formation in vitro
KR101892731B1 (ko) 구형 세라믹 과립 및 이의 제조방법
Balmayor et al. Starch-poly-ε-caprolactone microparticles reduce the needed amount of BMP-2
Jayasuriya et al. Rapid biomineralization of chitosan microparticles to apply in bone regeneration
WO2013119045A1 (fr) Différenciation neurale de cellules souches mésenchymateuses dans un hydrogel thermosensible et composition destinée à la différenciation neurale
WO2021040249A1 (fr) Matériau de greffe osseuse dérivé de foraminifère
WO2013012132A1 (fr) Procédé de fabrication d&#39;un échafaudage poreux en ciment de phosphate de calcium
Liu et al. Hierarchical microstructure design of multifunctional soft collagen-incorporated 3D hard polyetherketoneketone scaffolds for augmented bone regeneration

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: 18784272

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: 18784272

Country of ref document: EP

Kind code of ref document: A1