FR2778847A1 - Implants for sub-gingival injection comprising bio-resorbable microspheres containing an antiseptic or antibiotic - Google Patents
Implants for sub-gingival injection comprising bio-resorbable microspheres containing an antiseptic or antibiotic Download PDFInfo
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- FR2778847A1 FR2778847A1 FR9806415A FR9806415A FR2778847A1 FR 2778847 A1 FR2778847 A1 FR 2778847A1 FR 9806415 A FR9806415 A FR 9806415A FR 9806415 A FR9806415 A FR 9806415A FR 2778847 A1 FR2778847 A1 FR 2778847A1
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- microspheres
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- 239000004005 microsphere Substances 0.000 title claims abstract description 36
- 239000007943 implant Substances 0.000 title claims abstract description 16
- 230000002421 anti-septic effect Effects 0.000 title claims abstract description 6
- 230000003115 biocidal effect Effects 0.000 title claims abstract description 6
- 238000002347 injection Methods 0.000 title abstract 2
- 239000007924 injection Substances 0.000 title abstract 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000008119 colloidal silica Substances 0.000 claims abstract description 8
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 6
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 6
- 229920001577 copolymer Polymers 0.000 claims abstract description 5
- DTOUUUZOYKYHEP-UHFFFAOYSA-N 1,3-bis(2-ethylhexyl)-5-methyl-1,3-diazinan-5-amine Chemical compound CCCCC(CC)CN1CN(CC(CC)CCCC)CC(C)(N)C1 DTOUUUZOYKYHEP-UHFFFAOYSA-N 0.000 claims abstract description 3
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960003260 chlorhexidine Drugs 0.000 claims abstract description 3
- OQLKNTOKMBVBKV-UHFFFAOYSA-N hexamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCCOC1=CC=C(C(N)=N)C=C1 OQLKNTOKMBVBKV-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960001915 hexamidine Drugs 0.000 claims abstract description 3
- 229960004867 hexetidine Drugs 0.000 claims abstract description 3
- 239000003120 macrolide antibiotic agent Substances 0.000 claims abstract description 3
- 229940041033 macrolides Drugs 0.000 claims abstract description 3
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960000282 metronidazole Drugs 0.000 claims abstract description 3
- 235000019260 propionic acid Nutrition 0.000 claims abstract description 3
- 229940095574 propionic acid Drugs 0.000 claims abstract description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims abstract description 3
- 229920000642 polymer Polymers 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 5
- 229920002385 Sodium hyaluronate Polymers 0.000 claims description 3
- 229940010747 sodium hyaluronate Drugs 0.000 claims description 3
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 3
- 102000016736 Cyclin Human genes 0.000 claims description 2
- 108050006400 Cyclin Proteins 0.000 claims description 2
- 229920002988 biodegradable polymer Polymers 0.000 claims description 2
- 239000004621 biodegradable polymer Substances 0.000 claims description 2
- 239000000835 fiber Substances 0.000 claims description 2
- 208000028169 periodontal disease Diseases 0.000 claims description 2
- 210000002379 periodontal ligament Anatomy 0.000 claims description 2
- PJRSUKFWFKUDTH-JWDJOUOUSA-N (2s)-6-amino-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(N)=O PJRSUKFWFKUDTH-JWDJOUOUSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 108010021753 peptide-Gly-Leu-amide Proteins 0.000 claims 2
- 208000005888 Periodontal Pocket Diseases 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 210000002256 epithelial attachment Anatomy 0.000 claims 1
- 239000003349 gelling agent Substances 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 2
- ACTOXUHEUCPTEW-BWHGAVFKSA-N 2-[(4r,5s,6s,7r,9r,10r,11e,13e,16r)-6-[(2s,3r,4r,5s,6r)-5-[(2s,4r,5s,6s)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-[(2s,5s,6r)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-4-hydroxy-5-methoxy-9,16-dimethyl-2-o Chemical compound O([C@H]1/C=C/C=C/C[C@@H](C)OC(=O)C[C@@H](O)[C@@H]([C@H]([C@@H](CC=O)C[C@H]1C)O[C@H]1[C@@H]([C@H]([C@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(O)C2)[C@@H](C)O1)N(C)C)O)OC)[C@@H]1CC[C@H](N(C)C)[C@@H](C)O1 ACTOXUHEUCPTEW-BWHGAVFKSA-N 0.000 abstract 1
- JJTUDXZGHPGLLC-IMJSIDKUSA-N 4511-42-6 Chemical compound C[C@@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-IMJSIDKUSA-N 0.000 abstract 1
- 239000004187 Spiramycin Substances 0.000 abstract 1
- 239000002245 particle Substances 0.000 abstract 1
- 229920000747 poly(lactic acid) Polymers 0.000 abstract 1
- 239000004626 polylactic acid Substances 0.000 abstract 1
- 229960001294 spiramycin Drugs 0.000 abstract 1
- 229930191512 spiramycin Natural products 0.000 abstract 1
- 235000019372 spiramycin Nutrition 0.000 abstract 1
- 239000000499 gel Substances 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 229920002545 silicone oil Polymers 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000004568 cement Substances 0.000 description 3
- 238000005354 coacervation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000013265 extended release Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229940014041 hyaluronate Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 231100000956 nontoxicity Toxicity 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000003239 periodontal effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 241000243321 Cnidaria Species 0.000 description 1
- 229920000544 Gore-Tex Polymers 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0063—Periodont
-
- 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
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
La présente invention concerne un implant injectable en sous gingivalThe present invention relates to an injectable subgingival implant
résorbable en un temps déterminé. absorbable in a determined time.
Le domaine d 'utilisation de cet implant est la parodontologie et plus généralement tous les soins de chirurgie dentaire et le comblement des poches parodontales ou pyorées alvéo-dentaires L ' implant doit The field of use of this implant is periodontology and more generally all dental surgery care and the filling of periodontal or alveo-dental pyorea pockets. The implant must
permettre la restructuration et la reconstruction du sillon gingival et de I 'at- allow the restructuring and reconstruction of the gingival sulcus and the
tache épithéliale et. par son effet fibrosant, la mise en place d ' un faisceau de fibres secondaires en soutien du ligament parodontal et de la ligne amélo-cémentaire L 'implant pourra également colmater voire epithelial spot and. by its fibrosing effect, the establishment of a bundle of secondary fibers in support of the periodontal ligament and the amelo-cementary line The implant may also clog or even
remplacer le cément.replace the cement.
L' implant injectable est constitué de microsphères bio-résorbables en une période de 6 mois à 1 an et en suspension dans un gel également bio-résorbable en 3 mois. Les microsphères contiennent un ou plusieurs principes actifs de type antiseptique: hexétidine acide propionique, chlorhexidine, hexamidine ou de type antibiotique: macrolides, spiramicine cycline, métronidazole. Le rôle des principes actifs de type antiseptique ou antibiotique est, en se libérant lentement au fur et à mesure de la bio-dégradation des microsphères, de stopper toute prolifération The injectable implant consists of bio-absorbable microspheres in a period of 6 months to 1 year and suspended in a gel also bio-absorbable in 3 months. The microspheres contain one or more active principles of antiseptic type: hexetidine propionic acid, chlorhexidine, hexamidine or of antibiotic type: macrolides, spiramicin cyclin, metronidazole. The role of active principles of antiseptic or antibiotic type is, by slowly releasing as bio-degradation of the microspheres, to stop any proliferation
bactérienne et partant, de maintenir un environnement parodontal sain. bacterial and hence to maintain a healthy periodontal environment.
La dégradation des microsphères de polymères biodégradables de type copolymére d ' acide lactique - co-glycolique ( PLGA) en milieu Degradation of microspheres of biodegradable polymers of the lactic acid-co-glycolic acid (PLGA) type in medium
biologique se fait par un mécanisme chimique d ' hydrolyse non spécifique. biological is done by a chemical mechanism of non specific hydrolysis.
Les produits de cette hydrolyse sont ensuite métabolisés puis catabolisés The products of this hydrolysis are then metabolized and then catabolized
par le corps humain. L' hydrolyse chimique du PLGA est complète. by the human body. The chemical hydrolysis of PLGA is complete.
Les matières premières entrant dans la préparation de cet implant appartiennent à la famille des bio-matériaux d ' origine végétale, minérale ou bio-génétique Les microsphères sont réalisees à partir de deux copolymères d ' acide lactique -co-glycolique (PLGA): Poly (D.L-Lactide-co glycolide) 50:50 Resomer' RG 502 et Poly (DL-Lactide- co-glycolide) 75:25 The raw materials used in the preparation of this implant belong to the family of bio-materials of plant, mineral or bio-genetic origin. The microspheres are made from two copolymers of lactic-co-glycolic acid (PLGA): Poly (DL-Lactide-co glycolide) 50:50 Resomer 'RG 502 and Poly (DL-Lactide- co-glycolide) 75:25
Resomer' RG756. Le PLA cristallin peut également être utilisé. Resomer 'RG756. Crystalline PLA can also be used.
Les caractéristiques et les avantages du produit sont la facilité d' utilisation la seringuabilité du produit; la bio-disponibilité et résorbabilité contrôlée des microsphères de PLGA comme celle du gel vecteur; I' efficacité renforcée des microparticules de PLGA à libération contrôlée quant à leur effet désinfectant comblant, fibrosant etrestructurant au niveau de la ligne amélo-céméntaire le concept naturel du produit par sa formulation d ' origine végétale, minérale The characteristics and the advantages of the product are the ease of use and the syringability of the product; the bioavailability and controlled resorbability of PLGA microspheres like that of the vector gel; The enhanced effectiveness of PLGA microparticles with controlled release in terms of their filling disinfectant, fibrosing and restructuring effect on the amelo-cemetary line the natural concept of the product by its formulation of vegetable, mineral origin
et bio - génétique excluant tout test d' allergénicité préalable. and bio - genetics excluding any prior allergenicity test.
Les microsphères de PLGA à libération prolongée incorporées dans un gel de hyaluronates ou de silice colloldale proposent une alternative naturelle aux traitement des parodontopathies avec -2- déchaussement des dents par rapport aux traitements classiques: extraction The extended-release PLGA microspheres incorporated in a hyaluronate or colloidal silica gel offer a natural alternative to the treatment of periodontal disease with -2- loosening of the teeth compared to conventional treatments: extraction
dentaire, corail, goretex, implant suédois etc... souvent decevants. dental, coral, goretex, Swedish implant etc ... often disappointing.
Une technique de fabrication des micro-particules à libération prolongée incorporées dans un gel de hyaluronates ou de silice colloïdale a été retenue. Il s ' agit de la technique de coacervation simple par ajout d ' un second polymère au PLGA. Cette méthode consiste à disperser le principe actif retenu: antiseptique ou antibiotique dans une solution de polymère de type PLGA préalablement dissout dans une solution d' acétate d ' éthyle et à introduire un second polymère de type huile de silicone qui fait coacerver le polymère autour du principe actif sous forme d' un enrobage continu jusqu ' à la formation de microsphères. Le coacervat est ensuite dispersé dans un bain d 'heptane afin de durcir les microsphères par extraction du solvant organique et solubilisation de A technique for manufacturing sustained-release microparticles incorporated in a hyaluronate or colloidal silica gel was chosen. This is the simple coacervation technique by adding a second polymer to PLGA. This method consists in dispersing the active principle retained: antiseptic or antibiotic in a polymer solution of PLGA type previously dissolved in an ethyl acetate solution and in introducing a second polymer of silicone oil type which causes the polymer to coacerve around the active ingredient in the form of a continuous coating until the formation of microspheres. The coacervate is then dispersed in a heptane bath in order to harden the microspheres by extraction of the organic solvent and solubilization of.
I' huile de silicone. Une filtration permet de récupérer les microsphères. Silicone oil. Filtration makes it possible to recover the microspheres.
La méthode de coacervation simple permet d ' obtenir des micro- The simple coacervation method provides micro-
sphères bien individualisées de taille comprise entre 20 et 10qum, avec well individualized spheres of size between 20 and 10qum, with
une valeur moyenne de 50um.an average value of 50um.
Les microsphères de PLGA sont incluses dans un gel physiologique stérile et apyrogène dosé a 0,8% d ' acide hyaluronique de haut poids moléculaire ( sel de sodium). La teneur en hyaluronate de sodium est (2.5.22) ou de silice colloïdale à 5 %. Ce gel est utilisé uniquement comme vecteur afin de maintenir les microsphères en suspension. Il est résorbable en 3 mois environ, ce qui permet aux micospheres de PLGA à libération prolongée de réaliser lentement leur effet restructurant et fibrosant Les différents essais de seringuabilité du produit fini < microsphères de PLGA dans un gel physiologique d'acide hyaluronique à 0.8%) ont déterminé une viscosité suffisante du gel lui permettant de passer dans The PLGA microspheres are included in a sterile, pyrogen-free physiological gel dosed with 0.8% high molecular weight hyaluronic acid (sodium salt). The sodium hyaluronate content is (2.5.22) or 5% colloidal silica. This gel is used only as a vector in order to keep the microspheres in suspension. It is absorbable in about 3 months, which allows the PLGA micospheres of prolonged release to slowly realize their restructuring and fibrosing effect. The various tests of seringuability of the finished product (PLGA microspheres in a physiological gel of hyaluronic acid at 0.8%) have determined a sufficient viscosity of the gel allowing it to pass into
une aiguille de taille gauge 26 à gauge 30 et de préférence gauge 28. a needle of size gauge 26 to gauge 30 and preferably gauge 28.
Les microsphères de PLGA peuvent également être incluses dans un gel physiologique stérile et apyrogène dosé à 5% de silice colloïdale Partiellement résorbable à 3 mois la silice colloïdale possède la remarquable PLGA microspheres can also be included in a sterile and pyrogen-free physiological gel dosed with 5% colloidal silica Partially absorbable at 3 months colloidal silica has the remarkable
propriété - en se déshydratant - de former autour de la ligne amélo- property - when dehydrating - to form around the amelo-line
cémentaire un véritable ciment protecteur et. partant, de bloquer toutes migrations bactériennes au niveau du sillon gingival dont elle assure la cementitious a real protective cement and. therefore, to block all bacterial migrations at the level of the gingival groove which it ensures the
reconstruction.reconstruction.
Les deux gels décrits plus haut garderont leur bonne viscosité si le pourcentage de microsphères de PLGA dans les gels est de 5% à 40% et de préférence de 7% à 25% Le produit fini a été testé sur le lapin et le rat afin de s ' assurer de la non toxicité du produit et également afin de vérifier les périodes de résorbabilité du gel ( 3 mois) et des microsphères ( 6 mois à 1 an) -3- le PLGA dans une solution d ' acétate d' éthyle et à introduire un second polymère de type huile de silicone fait coacerver le polymère sous forme de micosphères. Le coacervat est ensuite dipersé dans un bain d 'heptane afin de durcir les microsphères par extraction du solvant organique et solubilisation de I ' huile de silicone. Une filtration permet de récupérer les microsphères The two gels described above will keep their good viscosity if the percentage of PLGA microspheres in the gels is from 5% to 40% and preferably from 7% to 25% The finished product has been tested on rabbits and rats in order to ensure the non-toxicity of the product and also in order to verify the periods of resorbability of the gel (3 months) and of the microspheres (6 months to 1 year) -3- the PLGA in a solution of ethyl acetate and at introducing a second polymer of silicone oil type makes the polymer coacerve in the form of micospheres. The coacervate is then dipers in a heptane bath in order to harden the microspheres by extraction of the organic solvent and solubilization of the silicone oil. Filtration to recover microspheres
La méthode de coacervation simple permet d ' obtenir des micro- The simple coacervation method provides micro-
sphères bien individualisées de taille comprise entre 20 et 100jum. avec well individualized spheres of size between 20 and 100jum. with
une valeur moyenne de 50um -an average value of 50um -
Les microsphères de PLGA sont incluses dans un gel physiologique stérile et apyrogène dosé a 0,8% d ' acide hyaluronique de haut poids moléculaire ( sel de sodium). La teneur en hyaluronate de sodium est (2.5.22) - Ce gel est utilisé uniquement comme vecteur afin de maintenir les microsphères en suspension. Il est résorbable en 3 mois environ. ce qui permet aux micosphères de PLGA à libération prolongée de réaliser The PLGA microspheres are included in a sterile, pyrogen-free physiological gel dosed with 0.8% high molecular weight hyaluronic acid (sodium salt). The sodium hyaluronate content is (2.5.22) - This gel is used only as a vector to keep the microspheres in suspension. It is absorbable in about 3 months. which allows the extended release PLGA micospheres to achieve
lentement leur effet restructurant et fibrosant. slowly their restructuring and fibrosing effect.
Les différents essais de seringuabilité du produit fini ( microsphères de PLGA dans un gel physiologique d'acide hyaluronique à 0.8%) ont déterminé une viscosité suffisante du gel lui permettant de passer dans The various tests for syringability of the finished product (PLGA microspheres in a physiological gel of hyaluronic acid at 0.8%) determined a sufficient viscosity of the gel allowing it to pass into
une aiguille de taille gauge 26 à gauge 30 et de préférence gauge 28. a needle of size gauge 26 to gauge 30 and preferably gauge 28.
Les microsphères de PLGA peuvent également être incluses dans un PLGA microspheres can also be included in a
gel physiologique sterile et apyrogène dosé à 5% de silice cololdale. sterile and pyrogen-free physiological gel dosed with 5% cololdal silica.
Partiellement résorbable à 3 mois la silice cololdale possède la remarquable Partially absorbable at 3 months, colloidal silica has the remarkable
propriété - en se déshydratant - de former autour de la ligne amélo- property - when dehydrating - to form around the amelo-line
cémentaire un véritable ciment protecteur et, partant, de bloquer toutes migrations bactériennes au niveau du sillon gingival dont elle assure la reconstruction Les deux gels decrits plus haut garderont leur bonne viscosité si le pourcentage de microsphères de PLGA dans les gels est de 5% à 40% et cementitious a real protective cement and, consequently, to block all bacterial migrations at the level of the gingival groove of which it ensures the reconstruction. The two gels described above will keep their good viscosity if the percentage of PLGA microspheres in the gels is from 5% to 40 % and
de préférence de 7% à 25%.preferably from 7% to 25%.
Le produit fini a été testé sur le lapin et le rat afin de s 'assurer de la non toxicité du produit et également afin de vérifier les périodes de The finished product has been tested on rabbits and rats to ensure the non-toxicity of the product and also to check the periods of
résorbabilité du gel < 3 mois) et des microsphères ( 6 mois à 1 an). resorbability of the gel <3 months) and of the microspheres (6 months to 1 year).
- 4 -- 4 -
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9806415A FR2778847A1 (en) | 1998-05-20 | 1998-05-20 | Implants for sub-gingival injection comprising bio-resorbable microspheres containing an antiseptic or antibiotic |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9806415A FR2778847A1 (en) | 1998-05-20 | 1998-05-20 | Implants for sub-gingival injection comprising bio-resorbable microspheres containing an antiseptic or antibiotic |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| FR2778847A1 true FR2778847A1 (en) | 1999-11-26 |
Family
ID=9526575
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR9806415A Withdrawn FR2778847A1 (en) | 1998-05-20 | 1998-05-20 | Implants for sub-gingival injection comprising bio-resorbable microspheres containing an antiseptic or antibiotic |
Country Status (1)
| Country | Link |
|---|---|
| FR (1) | FR2778847A1 (en) |
Cited By (8)
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| WO2001028591A2 (en) * | 1999-10-15 | 2001-04-26 | Genentech, Inc. | Injection vehicle for polymer-based formulations |
| EP1105095A2 (en) * | 1998-08-11 | 2001-06-13 | Quadrant Healthcare (UK) Limited | Biodegradable microparticles gel composition |
| FR2840193A1 (en) * | 2002-05-31 | 2003-12-05 | Textile Hi Tec | GASTRIC BAND |
| US6716251B1 (en) * | 1997-06-13 | 2004-04-06 | Aventis Pharmaceuticals Holdings, Inc. | Implant for subcutaneous or intradermal injection |
| US7651703B2 (en) | 1999-10-15 | 2010-01-26 | Genentech, Inc. | Injection vehicle for polymer-based formulations |
| RU2613299C1 (en) * | 2015-12-21 | 2017-03-15 | Федеральное государственное автономное образовательное учреждение высшего образования "Крымский федеральный университет имени В.И. Вернадского" | Method for treating diseases of parodontium, periodontium and oral cavity mucosa |
| CN110327497A (en) * | 2019-07-31 | 2019-10-15 | 易浦润（上海）生物技术有限公司 | A kind of injection gel and preparation method thereof containing microballoon |
| WO2020245074A1 (en) * | 2019-06-01 | 2020-12-10 | Lupin Holdings B.V. | Monodisperse resorbable polyester polymer compositions |
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6716251B1 (en) * | 1997-06-13 | 2004-04-06 | Aventis Pharmaceuticals Holdings, Inc. | Implant for subcutaneous or intradermal injection |
| US8414657B2 (en) | 1997-06-13 | 2013-04-09 | Valeant International Bermuda | Method for subcutaneous or intradermal injection |
| US7731758B2 (en) | 1997-06-13 | 2010-06-08 | Aventis Pharmaceuticals Holdings, Inc. | Implant for subcutaneous or intradermal injection |
| EP1105095A2 (en) * | 1998-08-11 | 2001-06-13 | Quadrant Healthcare (UK) Limited | Biodegradable microparticles gel composition |
| US7582311B1 (en) | 1999-10-15 | 2009-09-01 | Genentech, Inc. | Injection vehicle for polymer-based formulations |
| WO2001028591A2 (en) * | 1999-10-15 | 2001-04-26 | Genentech, Inc. | Injection vehicle for polymer-based formulations |
| US7651703B2 (en) | 1999-10-15 | 2010-01-26 | Genentech, Inc. | Injection vehicle for polymer-based formulations |
| WO2001028591A3 (en) * | 1999-10-15 | 2002-03-07 | Genentech Inc | Injection vehicle for polymer-based formulations |
| WO2003101352A1 (en) * | 2002-05-31 | 2003-12-11 | Textile Hi Tec | Gastric ring |
| FR2840193A1 (en) * | 2002-05-31 | 2003-12-05 | Textile Hi Tec | GASTRIC BAND |
| RU2613299C1 (en) * | 2015-12-21 | 2017-03-15 | Федеральное государственное автономное образовательное учреждение высшего образования "Крымский федеральный университет имени В.И. Вернадского" | Method for treating diseases of parodontium, periodontium and oral cavity mucosa |
| WO2020245074A1 (en) * | 2019-06-01 | 2020-12-10 | Lupin Holdings B.V. | Monodisperse resorbable polyester polymer compositions |
| CN114269327A (en) * | 2019-06-01 | 2022-04-01 | 纳诺米公司 | Monodisperse absorbable polyester polymer compositions |
| CN110327497A (en) * | 2019-07-31 | 2019-10-15 | 易浦润（上海）生物技术有限公司 | A kind of injection gel and preparation method thereof containing microballoon |
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