WO2020106118A1 - Composé polymère médical, composite médical et procédé de production de composite médical - Google Patents

Composé polymère médical, composite médical et procédé de production de composite médical

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Publication number
WO2020106118A1
WO2020106118A1 PCT/KR2019/016200 KR2019016200W WO2020106118A1 WO 2020106118 A1 WO2020106118 A1 WO 2020106118A1 KR 2019016200 W KR2019016200 W KR 2019016200W WO 2020106118 A1 WO2020106118 A1 WO 2020106118A1
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Prior art keywords
formula
plga
particles
pbmp
polymer compound
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PCT/KR2019/016200
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English (en)
Korean (ko)
Inventor
이연
강민지
김성환
강선아
박성배
박지웅
서지훈
Original Assignee
서울대학교 산학협력단
고려대학교 산학협력단
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Publication of WO2020106118A1 publication Critical patent/WO2020106118A1/fr

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    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0003—Not used, see subgroups
    • A61C8/0004—Consolidating natural teeth
    • A61C8/0006—Periodontal tissue or bone regeneration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A61F2/2846—Support means for bone substitute or for bone graft implants, e.g. membranes or plates for covering bone defects
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A61F2002/2817—Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
    • A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses

Definitions

  • R 1 is ,
  • the second aspect of the present invention is a substrate capable of supporting a bioactive material; And it includes a coating layer provided on the substrate, it is a polymer compound comprising a structural unit represented by the structural unit represented by the formula A and the formula B of the first aspect described above, provides a medical composite.
  • Formula A and Formula B of the first aspect of the present invention may be arranged in a line.
  • structural units of Chemical Formula A and Chemical Formula B may be provided in various forms such as a random copolymer, an alternating copolymer, a triblock copolymer, and a graft copolymer.
  • R 1 of Formula A of the first aspect of the present invention may be combined with a substrate, and R 2 of Formula B may be capable of binding with calcium ions.
  • the substrate may be sustained-release particles carrying a bioactive material, and R 1 may include a hydrophobic residue and interact with a hydrophobic substrate to enable stable binding.
  • the calcium ion may be a calcium-based biomaterial including teeth and bones, such as hydroxyapatite, and the R 2 may include a phosphate group to interact with the calcium ion to enable stable binding.
  • the term "scaffold" of the present invention means a solid support having a certain skeleton.
  • the scaffold may be a structure made of fibers having a diameter of 100 nm to 500 ⁇ m, but is not limited thereto.
  • hydroxyapatite (HA) in the present invention has the formula Ca 5 (PO 4 ) 3 (OH), but indicates that the crystal unit cell consists of two entities. It is usually written as Ca 10 (PO 4 ) 6 (OH) 2 . It is a compound of inorganic components that make up bones and teeth, that is, inorganic components composed of calcium and phosphorus. Therefore, it means that it is commonly used as a filler for replacing the cut bone or as a coating agent for promoting bone growth toward the artificial implant.
  • the term "calcium” of the present invention is a chemical element, the symbol in the periodic table is Ca, the atomic number is 20, and the atomic weight is 40.078. It is the most abundant metal element in living things. In particular, it is essential for humans and animals, and is present in bones and teeth and is one of the components of hydroxyapatite.
  • phosphate group of the present invention generally refers to a functional group derived from orthophosphoric acid.
  • the formula is represented by HOPO (OH) O- for monoesters, -OPO (OH) O- for diesters, and -OPO (O-) 2 for triesters.
  • Phosphoric acid esters are present in nature, and phosphoric acid groups play an important role in bioreactions, meaning that they are capable of strong binding with calcium ions, one of the components of hydroxyapatite.
  • the molecular weight of the polymer compound may be 1,000 to 500,000, but is not limited thereto.
  • the molecular weight of the polymer compound may be 40,000 to 60,000 passing through the glomerulus.
  • M and n in Formula 1 may be m: n 1:20 to 20: 1, but is not limited thereto.
  • the PBMP can be prepared as in Scheme 1 below.
  • the PBMP (4) is a butyl group of the BMA monomer, and can interact with the sustained-release particles through hydrophobic interactions, and the phosphomonoester group (phosphoric acid group) has teeth and bones like HA through electrostatic interaction. It can be stably bound by interacting with calcium ions on the surface of a biological material that is calcium-based.
  • the medical complex includes a substrate capable of supporting a bioactive material; And a coating layer provided on the substrate, wherein the coating layer may be a polymer compound comprising a structural unit represented by Formula A of the first aspect and a structural unit represented by Formula B below.
  • the substrate is polylactide-co-glycolide (PLGA), polyglycolide (PGA), polylactide, PLA ), Or polyepsilon caprolactone (poly ( ⁇ -caprolactone), P ( ⁇ -CL)), but is not limited thereto.
  • polylactide-co-glycolide (PLGA) of the present invention is a polymer material approved for medical use by the U.S. Food and Drug Administration and has no toxicity problem, so it is a drug delivery system or a biomaterial compared to other polymers. Direct medical applications, such as materials, have the advantage of being easier. In addition, it has a feature that can control the release behavior of the drug by changing the rate of decomposition of the polymer according to the control of the fraction or molecular weight of the glycolide and lactide during copolymerization. Means formulation.
  • the substrate may be PLGA
  • the polymer compound may be PBMP.
  • the polymer PBMP is coated on the PLGA to form PLGA / PBMP microparticles to provide a composite.
  • bioactive material of the present invention means a material capable of acting on physiological activity such as biofilm inhibition, antibiotic effect, anticancer effect, bone formation promotion, and inflammation inhibition.
  • the physiologically active substances are decay inhibitors Furanone C-30, antibiotic vancomycin, bone stimulating substance bone morphogenetic protein, inflammation inhibitor dexamethasone (dexamethasone) ), Or an immunosuppressive agent cyclosporine, but is not limited thereto.
  • the furanone C-30 refers to a tooth decay inhibitor that inhibits the adhesion and growth of the biofilm (Streptococcus mutans) present on the tooth surface.
  • the complex size may be 50 nm to 500 ⁇ m, but is not limited thereto.
  • the size of the complex When the size of the complex is less than 50 nm, its stability may be greatly deteriorated, and when it exceeds 500 ⁇ m, adhesion efficiency may be reduced on a calcium-based biomaterial.
  • the size of the complex may be about 50 nm to 100 ⁇ m.
  • the size of the complex may be about 100 nm to 500 ⁇ m.
  • the complex may be for drug delivery system use.
  • the complex is stably attached to the surface of the calcium-based biomaterial including HA and stably binds to the substrate, and there is no biotoxicity problem, so that the in vivo application may be safe. Therefore, it may be a drug delivery system that releases a bioactive substance carried in a substrate for a long period of time without side effects in the body.
  • the method of manufacturing a complex comprises: a first step of supporting a bioactive substance in sustained-release particles; And a second step of coating a polymer containing a sustained-release particle and a functional group that interacts with calcium ions on the sustained-release particle.
  • the first step it may be supported by adding 0.01 to 30% by weight of the bioactive substance relative to the sustained-release particles, but is not limited thereto.
  • the period of drug release may be short, resulting in insignificant physiological activity, and when it exceeds 30% by weight, a long duration may cause side effects.
  • the first step of loading may be carried at 0 to 60 ° C. for 1 to 12 hours, but is not limited thereto.
  • the physiologically active substance may not be sufficiently supported. If it exceeds 12 hours, the bioactive substance may be lost, and the uniformity of the sustained-release particles may be deteriorated. .
  • the polymer may be coated by adding 0.1 to 10% by weight of the sustained-release particles in the second step, but is not limited thereto.
  • the sustained-release particles When the polymer is less than 0.1% by weight, the sustained-release particles may not be completely enclosed, and when it exceeds 10% by weight, the sustained-release particles are weakened to lose physiologically active substances, and the uniformity and yield of the particles may be lowered.
  • the second step may be to coat by stirring for 0.25 hours to 6 hours, but is not limited thereto.
  • the coating efficiency of the polymer may be lowered, and if it exceeds 6 hours, the bioactive material may be lost and the yield may be lowered.
  • the polymer according to the first aspect of the present invention and the complex according to the second aspect are constituted by a drug delivery system, and thus are non-toxic, and the surface of the calcium-based biological material including teeth and bones, such as HA. It was confirmed that it can be applied to bacterial pathology and prevention by stably binding and releasing bioactive substances for a long time.
  • PLGA poly (lactide-co-glycolide) 75:25 (average Mw 48000 ⁇ 76000, catalog number 769797), polyvinyl alcohol (PVA) (average Mw 13000 ⁇ 23000, catalog number 348406), 2-hydride Hydroxyethyl methacrylate (HEMA), pyridine, butyl methacrylate (BMA), chloroform, 2,2'-azobis (2-methylpropio Nitrile) (AIBN: 2,2'-azobis (2-methylpropionitrile)), ethanol (EtOH), hydroxyapatite (HA), tetrahydrofuran (THF), crystal violet ( crystal violet (CV)) was purchased from Sigma-Aldrich (St. Louis, USA).
  • Dimethyl chlorophosphate was purchased from Acros-organics (Geel, Belgium). Furanone C-30 was purchased from Adipogen (San Diego, USA). Bromotrimethylsilane (TMSBr) was purchased from TCI (Tokyo, Japan). Dichloromethane (DCM), methanol (MeOH), and acetonitrile (ACN) were purchased from Samchun (Seoul, Korea). Minimum essential medium MEM) was purchased from Gibco (Waltham, USA).
  • Dulbecco's phosphate-buffered saline (DPBS) and fetal bovine serum (FBS) were purchased from WElGENE (Gyeongsan, Korea) Cell counting kit-8 (CCK-8)) was purchased from Dojindo (Tokyo, Japan) Brain heart infusion (BHI) was purchased from KisanBio (Seoul, Korea) S. mutans (ATCC 25175) It was purchased from KCTC (Daejeon, Korea) The LIVE / DEAD BacLight bacterial viability kit was purchased from Molecular Probes (ThermoFisher Scientific, MA, USA) Insert well was SPL Life Sciences ( Pocheon, Korea).
  • HA hydroxyapatite
  • PLGA / PBMP particles were dispersed in deionized water at a concentration of 50 mg / mL.
  • the HA disk prepared in Preparation Example 3 was immersed in a suspension at room temperature (ambient temperature) for 15 minutes. The disc was washed several times with deionized water and dried under vacuum for 12 hours.
  • PBMP The molecular weight distribution of PBMP was evaluated using GPC (Superdex200 10/300 GL column, GE Healthcare, UK). Phosphate buffered saline (PBS; 50 mM, pH 7.4, 150 mM NaCl) was used as the mobile phase. The flow rate was set to 0.5 mL / min, and polyethylene glycol (PEG) was used as standard.
  • PBS Phosphate buffered saline
  • PEG polyethylene glycol
  • Mn 9,860 g / mol and Mw is 23,300 g / mol for PBMP.
  • the multidispersity (PD Mw / Mn) value of 2.36 was in the typical molecular weight distribution range for free radical polymerization.
  • PBMP was designed as a polymer capable of binding to PLGA particles and stably binding to the HA surface, and was prepared in Reaction Scheme 1.
  • 1H-NMR analysis of (2) MOEP monomer, (3) poly (BMA-co-DMOEP) and (4) PBMP of Scheme 1 is shown in FIG. 10.
  • the material prepared in Preparation Example 2 was photographed with an electron microscope to analyze the shape of the fine particles.
  • the surface atomic composition of the PLGA and PLGA / PBMP particles of the present invention was analyzed using an XPS instrument (SIGMA PROBE, ThermoFisher Scientific, UK) equipped with a micro-focused monochromatic Al X-ray source. The C 1S , O 1S and P 2p regions were examined to confirm the presence of the PBMP coating.
  • PBMP polymer As shown in Figure 3, the presence of PBMP polymer on the surface of PLGA particles was confirmed by XPS.
  • PLGA and PLGA / PBMP particles showed C 1s and O 1s peaks at 286 and 532 eV, respectively.
  • the P 2p peak at 133 eV which is a characteristic of the phosphoric acid group, was observed only in the PLGA / PBMP particles, indicating the presence of PBMP in the outermost layer of the PLGA particles, indicating that PBMP was coated on the PLGA.
  • Comparative Example 1 Comparison of PLGA particles and PLGA / PBMP particles
  • the PLGA particles show a slight surface negative charge due to the terminal carboxylate, but do not have a high binding affinity to the HA surface. Therefore, after forming the PLGA fine particles, PBMP was added to coat the PLGA sustained-release particles. Both uncoated PLGA and PBMP coated (PLGA / PBMP) particles were generated in FIG. 2. (Size about 40-50 ⁇ m; Table 1).
  • the zeta potential of uncoated PLGA particles was about -11 mV, while the zeta potential of PBMP coated PLGA / PBMP particles was about -26 Mv.
  • PLGA / PBMP particles had a negative zeta potential compared to PLGA, and supported the successful coating of PBMP on the surface of PLGA particles.
  • Example 4 and Comparative Example 1 show that PBMP is coated and attached to the surface of PLGA particles without changing the spherical shape of PLGA.
  • Example 5 HA, PLGA, PLGA / PBMP particle adhesion test
  • the adhesive strength was tested by observing after shaking in water.
  • the PLGA / PBMP particles inhibited the decaying bacteria S. mutans by continuously releasing the decay inhibitor furanone C-30. Therefore, the particles of the present invention are effective to effectively suppress the physiological activity without side effects by stably attaching the particles carrying the bioactive inhibitor to surrounding tissues related to hydroxyapatite such as teeth and bones and continuously releasing the bioactive inhibitor.
  • the particles carrying the bioactive inhibitor are effective to effectively suppress the physiological activity without side effects by stably attaching the particles carrying the bioactive inhibitor to surrounding tissues related to hydroxyapatite such as teeth and bones and continuously releasing the bioactive inhibitor.
  • Example 11 Toxicity to osteoblasts against PLGA / PBMP particles
  • PLGA particles are widely accepted for their high biocompatibility, but the possibility of cytotoxicity of PLGA / PBMP particles to osteoblasts (MC3T3-E1 cells) was investigated.
  • the osteoblast cell line Preosteoblast (MC3T3-E1) cells were cultured in MEM and CO 2 (5% concentration) atmosphere supplemented with 10% FBS at 37 ° C. Cells were seeded on each HA disk sample coated with PLGA and PLGA / PBMP particles in 24-well plates at a density of 1 ⁇ 105 cells / well. After 24 hours incubation, the medium was removed and the disc was washed twice with DPBS. CCK-8 (Cell Counting Kit-8) solution was added to each disk and incubated at 37 ° C for 1 hour. The absorbance of the solution was measured using a microplate reader at 450 nm.
  • the complex coated with PLB particles that release the substance in a sustained release form with PBMP stably adheres to the bone-related tissues without cytotoxicity, and inhibits bacteria and physiology through continuous drug release. It can be seen that providing a drug delivery system that is easy for activity.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Developmental Biology & Embryology (AREA)
  • Dentistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un composé polymère médical, un composite médical et un procédé de production composite, et concerne un polymère, un composite ayant une particule formée par revêtement d'une base avec le polymère, et un procédé de production composite, le polymère comprenant : un groupe phosphate capable d'interagir avec un ion calcium sur la surface d'un biomatériau à base de calcium tel que l'hydroxyapatite ; et un résidu hydrophobe capable de se lier de manière stable à une particule à libération prolongée.
PCT/KR2019/016200 2018-11-23 2019-11-22 Composé polymère médical, composite médical et procédé de production de composite médical WO2020106118A1 (fr)

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KR10-2018-0146741 2018-11-23

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR19980084302A (ko) * 1997-05-22 1998-12-05 김윤 국소 투여형 생분해성 서방형 치주염 치료제 조성물 및 그 제조 방법
KR20160122656A (ko) * 2015-04-13 2016-10-24 서울대학교산학협력단 서방형 약물 전달체로서 히드록시아파타이트-칼슘설페이트 마이크로스피어
WO2018106666A1 (fr) * 2016-12-05 2018-06-14 Isp Investments Llc Copolymères et compositions pour soins buccaux et procédés d'utilisation

Patent Citations (3)

* Cited by examiner, † Cited by third party
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