WO2009046418A1 - Polymérisation par dépôt chimique en phase vapeur (cvd) sur des surfaces nucléophiles - Google Patents

Polymérisation par dépôt chimique en phase vapeur (cvd) sur des surfaces nucléophiles Download PDF

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WO2009046418A1
WO2009046418A1 PCT/US2008/078937 US2008078937W WO2009046418A1 WO 2009046418 A1 WO2009046418 A1 WO 2009046418A1 US 2008078937 W US2008078937 W US 2008078937W WO 2009046418 A1 WO2009046418 A1 WO 2009046418A1
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Prior art keywords
lactone
polymerization
bone
substrate
nucleophilic
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Jody Redepenning
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University of Nebraska Lincoln
University of Nebraska System
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00—Processes for applying liquids or other fluent materials
    • B05D1/60—Deposition of organic layers from vapour phase
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D167/00—Coating compositions based on polyesters obtained by reactions forming a carboxylic ester link in the main chain; Coating compositions based on derivatives of such polymers
    • C09D167/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones

Definitions

  • the material properties of bone are based on determinations of the elastic modulus, compressive arid tensile strengths. As a general rule, bone is stronger in compression than in tension and cortical is stronger than trabecular bone. Ranges of reported elastic modulus have been from 10 MPa to 25 GPa (10 MPa to 2 GPa for cancellous bone; 4 to 25 GPa far cortical and cancellous bone); compressive strength between 40 and 280 MPa (40 to 280 MPa for cancellous bone; 138 So 193 MPa for cortical bone); and tensile strength between 3.5 MPa and 150 MPa (3.5 to 150 MPa for cancellous bone; 69 to 133 MPa for cortical bone) (Friedlaender and Goldberg, Bone and Cartilage Allografts Park Ridge: American Academy of Orthopedic Surgeons 1991; Jarcho, "Calcium Phosphate Ceramics as Hard Tissue Prosthetics" Clin. Orthopedics and Related Research 157, 259
  • Mechanisms by which bone may fail include brittle fracture from impact loading and fatigue from constant or cyclic stress. Stresses may act in tension, compression, or shear along one or more of the axes of the bone- A synthetic bone substitute must resist failure by any of these stresses at their physiological levels. A factor of safety on the strength of the implant may ensure that the implant will be structurally sound when subject to hyperpliysiofogicai stresses.
  • a graft may be necessary when bone fails and does not repair itself in the normal amount of time or when bone loss occurs through fracture or tumor.
  • Bone grafts must serve a dual function: to provide mechanical stability and to be a source of osteogenesis. Since skeletal injuries are repaired by the regeneration of bone rather than by the formation of scar tissue, grafting is a viable means of promoting healing of osseous defects, as reviewed by Friediaeadef, G. £., "'Current Concepts Review: Bone Grafts," Journal of Bone and Joint Surgery, 69A(S), 786-790 (1987).
  • Osteoinduction and osteoconduction are two mechanisms by which a graft may stimulate the growth of new bone, ⁇ n the former case, inductive signals of little- understood nature lead to the plienotypic conversion of connective Ussuc cells to bone cells.
  • the implant provides a scaffold for bony ingrowth.
  • the bone remodeling cycle is a continuous event involving the resorption of pre-existing bone by osteoclasts and the formation of new bone by the work of osteoblasts. Normally, these two phases are synchronous and bone mass remains constant. However, the processes become uncoupled when bone defects heal and grafts are incorporated. Osteoclasts resorb the graft, a process which may take months. More porous grafts revascularize more quickly and graft resorption is more complete; After graft has been resorbed, bone formation begins. Bone mass and mechanical strength return to near normal.
  • grafts of organic and synthetic construction Three types of organic grafts are commonly used: autografts, allografts, and xenografts.
  • An autograft is tissue transplanted from one site to another In the patient. The benefits of using the patient's tissue are that the graft will not evoke a strong immune response and that the material is vascularized, which allows for speedy incoiporation.
  • using an autograft requires a second surgery, which increases the risk of infection and introduces additional weakness at the harvest site. Further, bone available for grafting may be removed from a limited number of site, for example, the fibula, ribs and iliac crest.
  • An allograft is tissue taken from a different organism of the same species, and a xenograft from an organism of a different species.
  • the latter types of tissue are readily available in larger quantities than autografts, but genetic differences between the donor and recipient may lead to rejection of the graft.
  • Synthetic implants may obviate many of the problems associated with organic grafts. Further, synthetics can be produced in a variety of stock shapes and sizes, enabling the surgeon to select implants as his needs dictate, as described by Coombes, A. D. A. and J. D. Heckjnan, "Gel Casting of Resorbable Polymers: Processing and Applications," Biomaterials, 13(4), 217-224 (1992). Metals, calcium phosphate ceramics and polymers have all been used in grafting applications.
  • Calcium phosphate ceramics are used as implants in the repair of bone defects because these materials are non-toxic, nott-immunogenic, and are composed of calcium and phosphate ions, the main constituents of bone r in an apatitic structure (Jarcho, 1981; Frame, J. W., "Hydroxyapatite as a biomaterial for alveolar ridge augmentation," M. J. Oral Maxillofacial Surgery, 16, 642-55 (1987); Parsons, et al. "Osteoconductive Composite Grouts for Orthopedic Use," Annals N.Y. Academy of Sciences, 523, 190-207 (1988)).
  • Calcium phosphate ceramics have a degree of bioresorbability which is governed by their chemistry and material structure, High density HA and TCP implants exhibit little resorption, while porous ones are more easily broken down by dissolution in body ⁇ uids and resorbed by phagocytosis. However, TCP degrades mure quickly than HA structures of the same porosity in vitro. In fact, FTA is relatively insoluble in aqueous environments.
  • the use of calcium phosphates in bone grafting has been investigated because of the chemical similarities between the ceramics and the mineral matrix found in the teeth and bones of vertebrates. This characteristic of the material makes it a good candidate as a source of osteogenesis.
  • the mechanical properties of calcium phosphate ceramics make them ill-suited to serve as a structural element. Ceramics are brittle and have low resistance to impact loading.
  • Biodegradable polymers are used in medicine as suture and pins for fracture fixation. These materials are well suited to implantation as they can serve as a temporary scaffold to be replaced by host tissue, degrade by hydrolysis to non-toxic products, and be excreted, as described by Kulkami, et al, J. Biomedical Materials Research, 5, 169-81 (1971); Hotlinger, J. O. and G. C. Battisto ⁇ c, "Biodegradable Bone Repair Materials.” Clinical Orthopedics and Related Research, 207, 290-305 (1986).
  • PDS poly(lactie acid)
  • PLA poly(glycolic acid)
  • PLAGA poly(glycolic acid)
  • PLAGA copolymers Copolynierization enables modulation of the degradation time of the material By changing the ratios of crystalline to amorphous polymers during polyme ⁇ zatioru properties of the resulting material can be altered to suit the needs of the application.
  • PLA is crystalline and a higher PLA content in a PLAGA copolymer results in a longer degradation time, a characteristic which may be desirable if a bone defect requires structural support for an extended period of time.
  • polyglycolide PGA
  • poly(lactide-co-glycolide PLGA
  • poly ⁇ D.L-lactide-co-trimethylene carbonate polyhydroxybutyrate
  • polyanhydrides such as poly(anhydride-co-imide) and co-polymers thereof are known to bioerode and are suitable for use in the present invention.
  • bioacfive glass compositions such as compositions including S1O2, Na ⁇ O, CaO, PiOs, AI 2 O3 and/or CaFs, maybe used.
  • Other useful bioer ⁇ dible polymers may include polysaccharides, peptides and fatty acids.
  • Bioerodible polymers are advantageously used in the preparation of bioresorbable hardware, such as but not limited to i ⁇ te ⁇ nedulary nails, pins, screws, plates and anchors for implantation at a bone site
  • the supplementary material itself is bioresorbable and is added to the PCA calcium phosphate in particulate or fiber form at volume fractions of 1 -50% and preferably, 1 -20 wt %.
  • the bioresorbable fiber is in the form of whiskers which interact with calcium phosphates according to the principles of composite design and fabrication known in the art.
  • Such hardware may be formed by pressing a powder particulate mixture of the PCA calcium phosphate and polymer.
  • a PCA calcium phosphate matrix is reinforced with PLLA fibers, using PLLA fibers similar to those described by Tormala el al., which is incorporated herein by reference, for the fabrication of biodegradable self reinforcing composites (Clin. Mater. 10:29-34 (1992)).
  • the implantable bioceramic composite may be prepared as a paste by addition of a fluid, such as water or a physiological fluid, to a mixture of a PCA calcium phosphate and a supplemental material.
  • a mixture of the supplementary material with hydrated precursor powders to the PCA calcium phosphate can be prepared as a paste or putty, [n cases where the supplementary material is to be dispersed within or reacted with a PCA calcium phosphate matrix, water maybe added to one of the precursor calcium phosphates to form a hydrated precursor paste, the resulting paste is mixed with the supplementary material, and the second calcium phosphate source is then added.
  • the calcium phosphate sources which make up the PCA calcium phosphate precursor powder may be premixed, water may then be added and then the supplementary material is added.
  • the fully hardened PCA calcium phosphate will be prepared in the desired form which will most often be of controlled particle size, and added directly to the matrix forming reaction (e.g., to gelling collagen). These materials may then be introduced into molds or be otherwise formed into the desired shapes and hardened at temperatures ranging from about 35-100° C.
  • a particularly useful approach is to form the composite precursor paste into the approximate shape or size and then harden the material in a m ⁇ sst environment at 37° C, The hardened composite may then be precisely milled or machined to the desired shape for use in the surgical setting.
  • the amount of particular PCA caicium phosphate to be incorporated into the supplemental material matrix will most often be determined empirically by testing the physical properties of the hardened composite according to the standards known to the art.
  • Composites comprising a porous, inorganic bone matrix derived from hone tissue and a compatible, bioabsorbable polymer or copolymer of a lactone monomer or mixture thereof have also been proposed wherein the composite is preferably prepared by the apatitic calcium phosphate, or an osteoinductive, bioabsorbable derivative thereof, initiated ring-opening polymerization or copolymerization of the lactone monomer within the pores of the porous inorganic bone matrix.
  • the invention in its broadest embodiment, relates to the chemical vapor deposition (CVD) polymerization or copoiyrnsrization of monomers onto nucleophiiic substrates that initiate or catalyze the polymerization of the monomers to form an adherent surface layer of the polymer or copolymer on the substrate
  • CVD chemical vapor deposition
  • a specific example of the method of the invention comprises the polymerization of a cyclic lactone such as L-lactide onto a nucleophilic substrate such as hydroxyapatite.
  • the mechanisms of chemical vapor deposition methods are, of course, well known in the art ["Chemical Vapor Polymerization: The Growth and Properties of ParySene Thin Films," J. B. Forttn and T.-H.
  • the method of the invention involves heating the monomer (e.g., L-lactide) under vacuum in the presence of the substrate (e.g., hydroxyapatite),
  • the substrate e.g., hydroxyapatite
  • the substrate is in contact only with the gas phase of the monomer.
  • the method of the invention forces gas phase monomer to collide with the nucleophilic surface.
  • the monomer can either react with the substrate or remain in the gas phase.
  • thin films of low molecular weight polymer are formed on the substrate surfaces exposed to the chemical vapor. As the reaction proceeds for longer times, both the thickness of the polymer coating and the molecular weight generally increase,
  • the method of the invention is particularly efficacious for porous samples wherein it is desired to provide a thin coating of polymer on the surface, but not to fit i the pores thereof. Because liquid monomer does not come in contact with the surface to be coated, there is no need to remove excess monomer from the surfaces of the final product. If porous samples are placed in contact with liquid monomer, the monomer has a tendency to stay within the pores due to capillary forces. In the CVD polymerization, method of the invention, the small amount of excess monomer remaining in the gas phase upon completion of the process is conveniently trapped in the monomer reservoir by cooling the reservoir before cooling the coated sample, As a result, the gas-phase monomer condenses into the monomer reservoir, not onto the sample,
  • lactone monomers that may be polymerized or copolymcrized according to the method of the invention include those having the formula:
  • -R.4 may be the same or different and are H 5 C1-C 1 6 straight or branched chain alkyl or HOCH 2 -.
  • Suitable lactone monomers that may be employed in the practice of the invention include any that form abioabsorbable polymer or copolymer such as, but not limited to caprolactone, t-butyl caprolactone, zeta-enantholactone, deltavalerolactones, the monoalkyl- dclta-valerolactones, e.g., the monomethyl-, monoethyl-, monohexyl-deltavalcroiactoncs, and the like; the nonalkyl, dialkyl, and trialkyl-epsilon-caprotactones, e g., the monomethyl-, monoethyl-, monohexyl-, dimethyl-, di-n-propyl-, di-n-hexyl-, trimethyl-, trielhyl-, tri- n-epsilon caprolactones, 5-nonyl-oxepan-2-one,
  • beta-butyrolactone gamma-lactones e.g., gammabutyrolactone or pivalolactone
  • dilactones e.g., lactide, dilactides, glycoHdes ⁇ e.g., tetramethyl glycolidcs, alkyl derivatives thereof and the like, ketodioxanones, e g> l ,4-dioxan-2-one, i,5-dioxepan-2-one, and the like.
  • the lactones can consist of the optically pure isomers or two or more optically different isomers or can consist of mixtures of isomers.
  • Any suitable substrate may be coated according to the CVD method described herein; e.g., those described herein below, as well as any nucleophilic surface that will initiate the cyclic lactone polymerization (metal oxides such as magnesium oxide), hydroxyapatite surfaces (including coralline, coral, bone, trabecular bone and bone that has been treated to convert at least apart of the surface thereof to calcium carbonate), BioGlass, and nucleophilic surface of biological sources of CaCO3, including for example nacre from gastropods (such as snails and abalone), cephalopoda (such as nacre from nautilus or cutilebone from cuttlefish), bivalve nacre (from scallops, clams, oysters or mussels), lobster shells, crab shells, and chicken egg shells, it will be understood by those skilled in the art that any of the nucleophilic surfaces described herein may also comprise derivatives wherein some fraction, of the native carbonate has been OH ⁇ exchanged with oxide, alkoxide or al
  • substitutions could be mad to hydroxyapatite and that the surface would still initiate polymerization of cyclic iations from the gas phase.
  • Such substitutions could include alkali metal ions (such as iilhium ions, sodium ions, and potassium ions), alkaline earth ions (such as magnesium Ions, strontium ions, and barium ions), transitions rnetal ions such as ferric ions, halide ions
  • Tiie rate of the CVD polymerization reaction is controlled by, inter alia, temperature. At least two mechanisms are believed to be involved. First, the vapor pressure of the monomer, i.e., the concentration of the monomer in the gas phase, is controlled by the temperature. The relationship between the vapor pressure of the monomer and the temperature is generally described by the well-known Clausius-ClapeyroB equation. Briefly, the vapor pressure of the gaseous monomer increases as the temperature increases. As the vapor pressure of the monomer increases, the number of collisions between the monomer and the substrate increase.
  • Carrying out the reaction in the presence of an inert gas may alter the resulting coating morphology and the rate of polymerization might well be somewhat different. Moreover, the rate of reaction would almost certainly be slower in the presence of an inert gas; depending, of course, on the amount of inert gas present.
  • Figure 1 shows a simple reaction vessel that can be used to perform the CVD polymerization of L-lactide onto hydroxyapatite.
  • the reaction vessel is a glass tube that is ultimately sealed while the contents are under vacuum just prior to initiating the process.
  • L-lactide is place in the bottom of the glass tube containing a constriction.
  • the sample to be coated via CVD polymerization is then added to the top of the glass tube, but the constriction in the tube prevents the sample from coming in contact with the solid L-lactide at the bottom of the vessel.
  • the glass tube is then sealed under vacuum.
  • the entire reaction vessel is then introduced into a convection oven that maintains the vessel (and its contents) at a constant temperature. For certain applications it might be desirable to ramp the temperature.
  • the temperature at which the reaction is performed is often above the melting temperature of the monomer, but the reaction is not limited thereto. Temperatures below the melting point may also be used.
  • the reaction is often run isothermally so that the vessel, the liquid (or solid) monomer, the sample, and the gas phase monomer moleewels are nominally at the same temperature.
  • the sample to be coated may, if desired, be held at a temperature higher than that of the monomer, If the temperature of the sample is lower than that of the monomer source, condensation of monomer may occur on the sample.
  • reaction vessel dimensions and sample configurations will produce CVD polymerizations in a manner that is consistent with the CVD polymerizations produced using the configuration shown in Figure I .
  • Biomet, Inc. markets ®Pro Osteon, a coralline hydraxyapatite that resembles the porous structure of trabecular bone.
  • Pro Osteon which is produced by converting a fraction of the calcium carbonate in goniopora coral to hydroxyapatite, is utilized as a substrate in the following examples to investigate the parameters necessary to control the CVD polymerization of L-lactide onto a porous surface. It will be understood, however, that the method of the invention is applicable to the CVD coating of any suitable porous surface.
  • Figure 2 shows a scanning electron micrograph (SEM) of as received coralline hydroxyapatite.
  • Figure 3 shows coralline hydroxyapatite after a thin coat of poly-L-lactide (PLLA) has been applied using the CVD polymerization method of the invention. Note that a relatively thin, but uniform coating of PLLA has been successfully applied by the method of the invention to this highly irregular substrate.
  • PLLA poly-L-lactide
  • the polymerization occurs within and throughout the macroscopic pores of the coralline hydroxyapatite because these pores are large compared to the mean free path of the gas phase monomer.
  • the pores of the coralline hydroxyapatite are filled with gas phase monomer during the course of the reaction.
  • the concentration of monomer in ihe gas phase is far lower than what is observed for liquid phase reactions and reactions from a melt, but the concentration in the gas phase is high enough to make the CVD polymerization viable.
  • EXAMPLE i provides additional details for one set of reaction conditions that are sufficient to execute CVD polymerizations of L-lactide onto coralline hydroxy apatite.
  • EXAMPLE 2 shows that the rate at which coralline hydroxyapatite can be coated with PLLA (by CVD polymerization) can be accelerated by heating the coralline hydroxyapatite to a temperature that is sufficient to convert a fraction of any residual calcium carbonate to calcium oxide.
  • the resulting mixture of hydroxyapatite, calcium ox ⁇ de r and residual calcium carbonate (in those cases where the conversion of calcium carbonate to calcium oxide is not driven to completion) serves as an effective nucleophilic surface for the CVD polymerization of L-lactide.
  • EXAMPLE 3 shows that goniopora coral can be dried at 400 C and then coated with PLLA (via CVD polymerization) without being converted to hydroxyapatite, as is done, for example, to produce Pro Osteon.
  • pure calcium carbonate is not a good nucleophilic surface for the polymerization of L-lactide, and although calcium carbonate is, by far, the predominant inorganic constituent in goniopora coral, it was found that goniopora coral is an effective heterogeneous initiator for the polymerization of L-lactide.
  • goniopora coral once it is dried, naturally contains a nucIcophiJc that is present at concentrations sufficient to initiate the polymerization at a rate that is useful.
  • a possible alternative is that approved procedures for isolating and processing goniopora corai introduce an effective nucleophile.
  • EXAMPLE 4 demonstrates that goniopora coral cars be thermally processed at elevated temperatures so that it can be coated rapidly with PLLA via the CVD polymerization method of the invention.
  • the process (described in more detail below) involves heating the goniopora coraf to a temperature sufficient to drive off carbon dioxide and convert some of the calcium carbonate to calcium oxide, The resulting oxide is a very strong nucleophile that is highly effective in initiating the desired ring opening polymerizations,
  • EXAMPLE 5 shows that the CVD polymerization of cyclic lactones is not limited to samples of goniopora coral or to samples derived from goruopora coral.
  • EXAMPLE 5 describes conditions that are efficacious for the CVD polymerization of L-Iactide into trabecular (porous) bone derived from bovine femurs.
  • CVD polymerizations we describe here are not limited to hydroxyapatite or to L-lactide.
  • Other cyclic lactones e.g., racemic lactide, glycolide, dioxanone and ⁇ -eaprolact ⁇ ne] will also react via lhis mechanism, as will other ⁇ cleophi Hc surfaces.
  • the coralline hydroxyapatite was supported inside the tube atop a constriction in the wall of the tube (See Figure 1.) This constriction prevented direct contact between the coralline hydroxyapatite samples, which remained above the constriction, and the solid (or liquid) L-lactide below the constriction in the bottom of the tube
  • the tubes were sealed under vacuum and then heated at temperatures that typically ranged from 75° C to 180° C for periods that typically ranged from 1 day to 10 days.
  • the samples were cooied to room temperature and then opened to give samples of coralline hydroxyapatite that were coated with poly-L-!actide, An SEM image of a coralline hydroxyapatite sample before it was coated with PLLA is shown in Figure 2.
  • the calcium carbonate that may be fo und in c ⁇ rall ine hydroxyapatite is a weak nucleophile that is not an efficacious initiator of L-lactide polymerization.
  • CaO is a very strong nucleophile that readily initiates the ring opening polymerization of L-lactide to PLLA.
  • Thermal processing of calcium carbonate can be used to convert it to CaO.
  • the calcium carbonate in coralline hydroxyapatite is slowly converted to calcium oxide.
  • the amount of calcium oxide that is produced can be controlled. Consequently, thermal processing can be used to increase the number of sites in coralline hydroxyapatite that can initiate L-lactide polymerization.
  • a specific example is described below.
  • a cylindrical rod of coralline hydroxyapatite (6 mm diameter by 12 mm length, 0.277 g) was heated to 600° C for a period of approximately 68 hours to remove deleterious water and to convert the majority of the CaCO 3 to CaO.
  • the sample which weighed 0.169 g, was removed from the heating oven and allowed to cool in a desiccator under vacuum.
  • approximately 0.3 g samples of L-lactide were placed in the bottom of c.a. 8 mm diameter glass tubes. The coral was supported inside the tube atop a constriction in the wail of the tube.
  • the sample was cooled to 400° C, and then transferred to a vacuum desiccator where it was allowed to cool to room temperature, During this time the sample experienced a 30% mass loss, which indicates that approximately two thirds of the original calcium carbonate had been converted to calcium oxide.
  • approximately 0.35 g of L-lactide were placed in the bottom of c.a. 8 mm diameter glass tubes.
  • the coral was supported inside the tube atop a constriction in the wall of the tube. (See Figure. 1.) This constriction prevented direct contact between the coral samples, which remained above the constriction, and the solid (or liquid) L-lactide below the constriction in the bottom of the tube.
  • Figure 10 shows the time dependent weight loss observed upon heating goniopora coral to 600° C in air.
  • Figure 10 serves only as an example.
  • the rate of conversion cars be controlled by controlling the temperature. Generally speaking, temperatures higher than 600° C produce faster rates of conversion than the rate shown in Figure 10. Temperatures lower than 600° C produce slower rates of conversion than the rate shown in Figure 10.
  • Figure 11 shows a sample of gon ⁇ opora com! for which the CaCO 3 has been converted, effectively completely, to CaO, The porosity of this material on a length scale less than 10 ⁇ m is particularly noteworthy,
  • Cylindrical plugs (6 mm dia and 20 imrt length) of trabecular bone were cut from the proximal end of a bovine femur. These sections were placed in a soxhlet extractor to remove the majority of the organic material from the bone.
  • the solvent mixture used in the soxhlet extractor was 80% ethylcnediamine (240 ml) and 20% deionized water (60 ml). This mixture was observed to reflux at 118-120° C, The samples were extracted for approximately 40 hours, over which time at least one hundred extraction cycles were executed, At the end of this time, the extracted organic material ethylenediamine/water mixture was removed from the soxhlet extractor and replaced with deionized water.
  • Soxhlet extraction of trabecular bone using water was continued until washings from individual extractions were found to be neutral. At this point the samples were white to the unaided eye,, but a few percent organic material (by weight) remained. The remaining organic material was removed by heating the extracted sample to 600° C in air for approximately 40 hours. The samples were then cooled to room temperature under vacuum in a desiccator. The desiccator was brought into a nitrogen box.

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  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

Procédé de préparation d'un composite qui comprend un polymère ou un copolymère bio-absorbable d'un ou de plusieurs monomères de lactone et un substrat. Le procédé comprend le déclenchement d'une polymérisation ou d'une copolymérisation par ouverture du cycle de la lactone. Le déclenchement de la polymérisation ou de la copolymérisation de la lactone peut être effectué par un procédé de dépôt chimique en phase vapeur. Le substrat peut être positionné dans un réacteur de dépôt chimique en phase vapeur et exposé à une vapeur de monomères de lactone dans des conditions qui permettent de déclencher une polymérisation ou une copolymérisation par ouverture de cycle de la lactone par le substrat et un dépôt du polymère ou du copolymère sur le substrat.
PCT/US2008/078937 2007-10-04 2008-10-06 Polymérisation par dépôt chimique en phase vapeur (cvd) sur des surfaces nucléophiles Ceased WO2009046418A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108456868A (zh) * 2018-02-06 2018-08-28 江苏微导纳米装备科技有限公司 一种聚内酯薄膜制备方法

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US5620698A (en) * 1995-03-06 1997-04-15 Ethicon, Inc. Blends of absorbable polyoxaesters containing amines and/or amido groups
US5747390A (en) * 1994-11-30 1998-05-05 Ethicon, Inc. Hard tissue bone cements and substitutes
US6436481B1 (en) * 1996-12-23 2002-08-20 Novartis Ag Method of producing a reactive coating by after-glow plasma polymerization
US6630243B2 (en) * 1999-05-20 2003-10-07 Bausch & Lomb Incorporated Surface treatment of silicone hydrogel contact lenses comprising hydrophilic polymer chains attached to an intermediate carbon coating

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5747390A (en) * 1994-11-30 1998-05-05 Ethicon, Inc. Hard tissue bone cements and substitutes
US5620698A (en) * 1995-03-06 1997-04-15 Ethicon, Inc. Blends of absorbable polyoxaesters containing amines and/or amido groups
US6436481B1 (en) * 1996-12-23 2002-08-20 Novartis Ag Method of producing a reactive coating by after-glow plasma polymerization
US6630243B2 (en) * 1999-05-20 2003-10-07 Bausch & Lomb Incorporated Surface treatment of silicone hydrogel contact lenses comprising hydrophilic polymer chains attached to an intermediate carbon coating

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108456868A (zh) * 2018-02-06 2018-08-28 江苏微导纳米装备科技有限公司 一种聚内酯薄膜制备方法

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