WO2007093662A1 - Monomères et polymères acryliques dérivés de l'eugénol, préparations et compositions les contenant et leurs applications biomédicales - Google Patents

Monomères et polymères acryliques dérivés de l'eugénol, préparations et compositions les contenant et leurs applications biomédicales Download PDF

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WO2007093662A1
WO2007093662A1 PCT/ES2007/070031 ES2007070031W WO2007093662A1 WO 2007093662 A1 WO2007093662 A1 WO 2007093662A1 ES 2007070031 W ES2007070031 W ES 2007070031W WO 2007093662 A1 WO2007093662 A1 WO 2007093662A1
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eugenol
butyl
methacrylate
ethyl
methyl
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PCT/ES2007/070031
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Spanish (es)
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Luis Rojo Del Olmo
Maria Blanca Vazquez Lasa
Julio San Roman Del Barrio
Sanjukta Deb
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Consejo Superior De Investigaciones Científicas
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/40—Esters of unsaturated alcohols, e.g. allyl (meth)acrylate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C13/00—Dental prostheses; Making same
    • 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
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
    • C07C69/533—Monocarboxylic acid esters having only one carbon-to-carbon double bond
    • C07C69/54—Acrylic acid esters; Methacrylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
    • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
    • C08F20/10—Esters
    • C08F20/12—Esters of monohydric alcohols or phenols
    • C08F20/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
    • C08F20/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents

Definitions

  • This invention is part of the self-healing formulations that are used as controlled release systems for medications in minimally invasive surgery and dental applications.
  • Eugenol (4-allyl-2-methoxyphenol) is a product of natural origin that is found as the main component of essential oils, specifically it is the main constituent of clove essence. This compound has analgesic and antiseptic properties, being one of the most commonly used products for pain relief of irritated or diseased dental pulp (Sticht FD, Smith PM. "Eugenol: Some pharmacologic observations”. J Dent Res 1971, 50, 1531-1535). Low concentrations of Eugenol have anti-inflammatory effects on dental pulp but high concentrations can be cytotoxic.
  • the present invention is related to the preparation of monomeric compounds derived from Eugenol, the synthesis of polymers and copolymers from the derivatives obtained as well as the development of self-healing acrylic formulations bearing Eugenol with acrylic and polyacrylic components. These systems have analgesic and antiseptic properties from the chemically anchored Eugenol molecule to macromolecular chains. These self-healing formulations can be applied directly when used as dental resins, or they can be injected when used in the treatment of osteoporotic fractures in minimally invasive surgery.
  • the present invention is based on the fact that the inventors have developed a monomeric acrylic compound derived from Eugenol of general structure such as that presented in Formula (I), capable of polymerizing and copolymerizing with acrylic monomers and of being part in liquid phase compositions of self-healing formulations.
  • the polymers or copolymers thus obtained can be used in the preparation of the solid phase composition of self-healing formulations alone or in conjunction with other commercial polymers. In relation to these polymers it was observed that cell viability is not affected by the presence of the extracts of any of these released polymers or copolymers (see Example 6).
  • an object of the present invention is an acrylic monomer derived from Eugenol, hereinafter acrylic monomer of the invention, of general formula (I)
  • n 0, 2, 6 or 11
  • Ri is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • R.2 is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • R 3 is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • the acrylic monomer of the invention can group several families of compounds. So, an object Particular of the invention is an acrylic monomer of the general formula Ia:
  • Ri is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • R.2 is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • R 3 is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • a particular embodiment of the invention is the acrylic compound of the invention, belonging to the formula Ia, eugenyl methacrylate
  • Another particular object of the invention is an acrylic monomer of the general formula Ib
  • n 2, 6 or 11.
  • Ri is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • R.2 is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • R 3 is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical.
  • Another particular embodiment of the invention is the acrylic compound derived from Eugenol, belonging to the formula Ib, ethoxyieugenyl methacrylate (EEgMA) (Example 2).
  • Another object of the invention is a process for obtaining the acrylic monomer of the invention, hereinafter procedure for obtaining the acrylic monomer, and more preferably of the compounds belonging to the general formula Ia which is carried out under mild conditions and because it comprises the following steps (see Example 1): i) Eugenol is dissolved with triethylamine in stoichiometric amounts, using diethyl ether as a solvent at room temperature, ii) under a nitrogen atmosphere, a stoichiometric amount of methacryloyl chloride is added dropwise to the solution of i) and allowed to react for 48 hours at room temperature under stirring, and iii) the acrylic monomer is isolated and purified as a reaction product.
  • Another particular object is a process for obtaining an acrylic monomer of the invention, preferably belonging to the general formula Ib characterized in that it is carried out under mild conditions and because it comprises the following steps: i) synthesis of 1-hydroxy, n- alkyl Eugenol by treatment of Eugenol with the corresponding OC, G ⁇ -chloro-alkyl alcohol in a hydroalcoholic medium, applying a Williamson reaction [March 's advanced organic chemictry (5th Edition) BM Smith and J. March. John Wiley and Sons. New York 2001].
  • the purification of the Eugenol acrylic monomer of the invention can be carried out by different techniques, preferably by a silica chromatographic column.
  • the acrylic monomer of the invention can also be used for the preparation of a polymer or a copolymer carrying Eugenol.
  • Another object of the invention is a polymer carrying Eugenol, hereinafter acrylic polymer of the invention, comprising an acrylic monomer derived from
  • Another particular object of the invention is the acrylic polymer of the invention where the polymer is a copolymer comprising an acrylic monomer derived from Eugenol of general formula (I) and a second acrylic monomer different from the previous one belonging, by way of illustration and without limit the scope of the invention, to the following group: methyl methacrylate (MMA) or ethyl methacrylate (EMA).
  • MMA methyl methacrylate
  • EMA ethyl methacrylate
  • Another particular embodiment of the invention is a copolymer of the invention, by way of illustration and without limiting the scope of the invention, belonging to the following group: eugenyl methacrylate-ethyl methacrylate (EgMA / EMA) copolymer and methacrylate copolymer of ethyl ethoxynethylene methacrylate (EEgMA / EMA) (see Example 4).
  • EgMA / EMA eugenyl methacrylate-ethyl methacrylate
  • EEgMA / EMA methacrylate copolymer of ethyl ethoxynethylene methacrylate
  • Another object of the invention is a process for obtaining the acrylic polymer of the invention comprising a radical polymerization step of any of the monomeric compounds of general formula (I), and is carried out by dissolving the corresponding monomer in toluene, using azobisisobutyronitrile (AIBN) as a radical initiator and at a temperature of 50-60 ° C.
  • AIBN azobisisobutyronitrile
  • the process for obtaining comprises a copolymerization step in the presence of a radical initiator of any of the compounds of general formula (I) as the first monomer, with a different acrylic monomer as the second belonging monomer, by way of illustration and without limiting the scope of the invention, to the following group: methyl methacrylate (MMA) or ethyl methacrylate (EMA).
  • MMA methyl methacrylate
  • EMA ethyl methacrylate
  • the Eugenol-derived acrylic monomers and polymers of the invention can be used in the preparation of a self-curable formulation comprising a system of two compositions or phases: a liquid phase and a solid phase.
  • another object of the invention is a self-curable formulation, hereinafter self-curable formulation of the invention, of acrylic systems derived from Eugenol comprising two compositions or phases: a liquid phase and a solid phase.
  • Another particular object of the invention is a self-curable formulation of the invention in which the self-healing acrylic liquid phase composition comprises one or more of the Eugenol-derived acrylic monomers of the invention, in an amount between 20-60% - p with respect to the total weight of the liquid phase, and a second acrylic monomer in an amount between 80-40% -p with respect to the total weight of the liquid phase belonging, by way of illustration and without limiting the scope of the invention, to the following group: methyl methacrylate (MMA) or ethyl methacrylate (EMA).
  • MMA methyl methacrylate
  • EMA ethyl methacrylate
  • the self-curing liquid phase acrylic composition of the formulation of the invention comprises an aromatic tertiary amine as an activator in an amount between 0.5-2.5% -p, preferably 2% -p, and one or more inhibitors in an amount of up to 0.01% -p.
  • the inhibitor used may, for example, belong to the family of quinones.
  • Another particular object of the invention is a self-curable formulation of the invention in which the self-curing solid-phase acrylic composition comprises prepolymerized poly (methyl methacrylate) (PMMA), or prepolymerized poly (ethyl methacrylate) (PEMA) particles.
  • PMMA methyl methacrylate
  • PEMA prepolymerized poly (ethyl methacrylate) particles.
  • copolymers of MMA or EMA with other monomers present in an amount comprised between 20-80% -p with respect to the total weight of the solid phase.
  • other polymers or copolymers that can be used in the solid phase composition are the polymers or copolymers described in the present invention.
  • the self-healing acrylic solid phase composition of the formulation of the invention can also comprise zinc oxide (ZnO) in an amount between 50-80% -p with respect to the total weight of the solid phase (see Example 8).
  • the self-curing acrylic solid phase composition may also comprise one or more initiators in an amount of up to 3% -p, for example benzoyl peroxide, and / or one or more radiopaque agents in an amount between 20-25% -p with respect to the total weight of the solid phase belonging, by way of illustration and without limiting the scope of the invention: barium sulfate, zirconium dioxide, tantalum oxide, strontium oxide and organic compounds.
  • Another particular embodiment of the invention is a self-curable formulation of the invention comprising a liquid phase composition with monomers of eugenyl methacrylate (EgMA) and methyl methacrylate
  • MMA in varying proportions, with the compound (4-N, N-dimethylaminophenyl) -methanol (DMOH) as activator, and a solid phase composition based on poly (methyl methacrylate) (PMMA), or similarly with ethoxyethylene methacrylate without or with zinc oxide (see Examples 7 and 8).
  • acrylic compositions - liquid and solid - of the formulation of the invention once mixed allow their handling and application for a controlled time and harden or cure, by means of a radical polymerization process of the liquid phase, to give rise to polymeric systems that are They adapt perfectly to dental and bone cavities where they are applied.
  • another object of the invention is the use of the self-curable formulation of the invention, by mixing the liquid and solid phase compositions that compose it and its direct application or by injection and finally curing "in situ" for reconstruction. , temporary or permanent, dental and bone.
  • Another particular embodiment is the use of the self-curable formulation of the invention in which bone reconstruction consists of a vertebra fixation or biomechanical fixation of osteoporotic fractures in minimally invasive surgery in the field of traumatology and orthopedic surgery.
  • FIGURES Figure 1.- Diagram of the 95% confidence limit for the values of the reactivity ratios of the EgMA / EMA and EEgMA / EMA copolymers determined by the treatment proposed by Tidwell and Mortimer.
  • Figure 4 ESEM images (scanning electron microscope) of the colonization of human fibroblasts on the TMX control and on PEMA, PEgMA, PEEgMA, EgMA / EMA 50/50 copolymer and EEgMA / EMA 50/50 copolymer, at 24 and 48 hours after planting.
  • Figure 5 Results of the MTT cytotoxicity test for the TMX control and for the systems studied, PEMA, PEgMA (designated Eg), copolymers EgMA / EMA (designated E Eg), PEEgMA (designated EEg) and copolymers EEgMA / EMA (designated E EEg).
  • the purity of the analyzed product is greater than 98% and its chemical structure is shown in the following Figure:
  • the synthesis of ethoxyethylene methacrylate proceeds in two steps.
  • the reaction medium is refluxed for 24 h.
  • the reaction product is purified by chromatographic column with ethyl acetate / hexane 30/70.
  • the second step carries with it the esterification reaction of 2-eugenyl ethanol which is carried out by dissolving it in diethyl ether in a three-mouth flask. An equimolecular amount of triethylamine is added to the solution as the reaction catalyst and constant stirring is maintained. An equimolecular amount of methacryloyl chloride is then added dropwise under a nitrogen atmosphere. Stirring is maintained and allowed to react for 48 h at room temperature. The reaction mixture is filtered to separate the amine hydrochloride formed. Finally, the reaction solid is isolated by solvent extraction under reduced pressure.
  • Etoxieugenyl methacrylate (EEgMA) is purified by chromatographic column with 10/90 ethyl acetate / hexane. The resulting product is characterized by nuclear magnetic resonance (NMR) using deuterated chloroform (CI 3 DC) as solvent and tetramethylsilane (TMS) as internal reference.
  • NMR nuclear magnetic resonance
  • CI 3 DC deuterated chloroform
  • TMS tetramethylsilane
  • Example 3 Preparation of poly (eugenyl methacrylate) (PEgMA) and poly (ethoxygiene) methacrylate (PEEgMA) polymers.
  • the polymerization reaction of the corresponding Eugenol derivative is carried out in dissolution of the monomer in toluene (IM) and azobisisobutyronitrile (AIBN) is used as the radical initiator at a concentration of 1% -p with respect to the monomer.
  • the reaction temperature is 50 ° C and the reaction time is 24 hours to obtain high conversion polymers or the reaction time is adjusted to achieve conversions below 10% -p.
  • the reaction mixture is precipitated in hexane, the precipitated solid is filtered, washed successively and dried until constant weighing.
  • the polymers obtained at conversion less than 10% -p are soluble white powders and are characterized by proton nuclear magnetic resonance ( 1 H-NMR).
  • reaction yields are 60% and 70% for PEgMA and PEEgMA, respectively.
  • the reaction products are subjected to extraction in Soxhlet with toluene for 48 hours and percentages of soluble polymer of 1.06 and 0.6% are obtained for the PEgMA and PEEgMA respectively.
  • the reactivity ratios are calculated from the composition values using both the Finemann-Ross and Kelen-Tüdos linear methods, as well as the non-linear methods of Tidwell-Mortimer and Levenberg-Marquardt. The values of the reactivity ratios are shown in Table I.
  • FIG.1 the diagram of 95% confidence obtained by application of the mathematical treatment proposed by Tidwell and Mortimer is shown. From the values of the reactivity parameters it can be deduced that both macromolecular radicals whose active end in growth is a unit of EMA and a unit of the acrylic derivative of eugenyl have a greater reactivity against the carrier monomer of Eugenol. The product of the reactivity ratios (rix r 2 ) less than the unit in both systems indicates that the copolymers prepared under the reaction conditions above These have a distribution of predominantly random units.
  • Example 5 Cytotoxicity of EgMA and EEgMA. compared to that of Eugenol.
  • the culture medium is Minimal Essential Medium Eagle (MEM) modified with HEPES and enriched with 10% fetal bovine serum (FBS), 200 rtiM L-glutamine, 100 units / ml penicillin and 100 ⁇ g / ml streptomycin.
  • the culture medium is changed at selected time intervals.
  • Thermanox® (TMX) is used as a negative control.
  • the corresponding monomer is mixed with the Tween 80 surfactant in a 3: 1 weight ratio.
  • the mixture is dispersed in serum-free medium to obtain a solution of the mixture containing 0.0075% -p of monomer and 0.025% -p of surfactant.
  • This solution is diluted successively with serum free medium.
  • Human fibroblasts are seeded at a density of 11 x 10 4 cells / ml in complete medium in a 96-well culture plate and incubated until confluence. After 24 hours of incubation, the medium is replaced with the corresponding dilution and incubated at 37 ° C in an atmosphere of humidified air with 5% CO2 for 24 h.
  • a solution of 3- (4, 5-dimethylthiazol-2-yl) -2.5-diphenyltetrazolium (MTT) bromide in a warm phosphate buffer (PBS) solution (0.5 mg / ml) is prepared and the plates are incubated at 37 ° C for 4 h.
  • PBS warm phosphate buffer
  • DMSO dimethylsulfoxide
  • Relative cell viability 100 x (D0 M - D0 B ) / D0 c
  • Example 6 Biocompatibility of PEgMA, PEEgMA. and copolymers EgMA / EMA and EEgMA / EMA.
  • the biocompatibility of polymers and copolymers is evaluated by direct contact of the cells with the corresponding material.
  • the corresponding material is placed in a 24-well plate (in duplicate) that are seeded with human fibroblasts at a density of 14 x 10 4 cells / ml and incubated at 37 ° C for 24 hours.
  • the cells are then fixed with 1.5% glutaraldehyde buffered with a 0.1 M phosphate buffer.
  • the dried samples are coated with a gold layer before being examined by scanning electron microscopy (ESEM) using a voltage of 15 KeV
  • ESEM scanning electron microscopy
  • the cells adopt a normal morphology and appear well extended on the surface of any of the Eugenol-bearing polymers or copolymers, indicating the formation of stable adhesions and contacts, and this fact can be considered as a sign of good Biocompatibility for all these materials.
  • the cytotoxicity from any extract of the material is analyzed by the MTT test.
  • disks (10 mm in diameter and 1 mm thick) of the corresponding polymers and copolymers obtained at high conversion by reaction of the monomer or mass monomers are used, using AIBN as a radical initiator, at 50 ° C temperature and during a reaction time of 24 hours.
  • the discs are washed and dried before use.
  • the disks thus obtained and the negative control TMX is immersed in 5 ml of FBS-free MEM. Then introduced into a rotary mixer at 37 0 C, the medium at different times (1, 2 and 7 days) is removed and replaced with another 5 ml of fresh medium. All extracts are obtained under sterile conditions.
  • Human fibroblasts are seeded at a density of 11 x 10 4 cells / ml in complete medium in a sterile 96-well culture plate and incubated at confluence. Then, the medium is replaced with the corresponding eluted extract and incubated at 37 ° C in a humidified air atmosphere with 5% CO2 for 24 hours. A solution of MTT in a warm phosphate buffer (PBS) solution is prepared and filtered before use. 10 ⁇ l of MTT is added to each well to give a final concentration of 0.5 mg / ml, and the plates are incubated at 37 ° C for 4 hours.
  • PBS phosphate buffer
  • Example 7 Self-healing acrylic formulations of eugenyl methacrylate with acrylic and polyacrylic components.
  • Self-healing compositions of acrylic systems are formulated using a two-phase system as mentioned in the Detailed Description of the Invention.
  • One of the phases is a liquid composed of the monomers of eugenyl methacrylate (EgMA) and methyl methacrylate (MMA) in varying proportions, using the compound (4-N, N-dimethylaminophenyl) -methanol (DMOH) as activator.
  • EgMA eugenyl methacrylate
  • MMA methyl methacrylate
  • DMOH 4-N, N-dimethylaminophenyl
  • the second phase consists of a solid based on poly (methyl methacrylate) (PMMA). It is possible to use this component directly (for example commercial PMMA pearls such as Bonar, or the beads of a "Self-curing Resin, etc.) or the solid component of other commercial formulations such as DuraLay. As a solid phase in Example 7, they have been used the pearls of the "Self-curing Resin” and the solid phase of the Duralay commercial formulation, which are referred to herein as Res. Autopol. and DuraLay respectively.
  • PMMA poly (methyl methacrylate)
  • Curing parameters are determined according to ISO 5833 (International Standard ISO 5833. Implants for Surgery-Acrylic Resins Cements. 1992).
  • the time of the pasty state (t p ) represents the time in which the two phases are mixed forming the paste prior to its introduction to the mold, a moment that is considered when the paste does not adhere to the surgical glove.
  • the setting time (tf) is determined as the time at which the cement mass temperature is the arithmetic mean of the maximum temperature in ° C and the ambient temperature, 23 ⁇ 1 ° C.
  • the working time (t t ) is calculated as the difference between the setting time and the time of the pasty state.
  • the peak or maximum temperature (T max ) is defined as the maximum temperature reached during the polymerization reaction.
  • Table III Maximum temperature values (T 3 ⁇ 13x ), pasty state times (t p ), setting (t f ), and work (t t ) obtained in curing acrylic formulations with eugenyl methacrylate.
  • Example 8 Self-healing acrylic formulations of eugenyl methacrylate with acrylic and polyacrylic components in the presence of zinc oxide.
  • Autocurable compositions of acrylic systems are formulated using a liquid phase composed of the monomers of eugenyl methacrylate (EgMA) and methyl methacrylate (MMA), using as compound the compound (4- N, N-dimethylaminophenyl) -methanol (DMOH).
  • EgMA eugenyl methacrylate
  • MMA methyl methacrylate
  • the solid phase is composed of zinc oxide (ZnO) particles and poly (methyl methacrylate) (Plexigum, Merck) particles, in different proportions, using benzoyl peroxide (BPO) as the radical initiator.
  • BPO benzoyl peroxide
  • MMA Methyl Methacrylate
  • Table V Maximum temperature values (T 2 S 113x ), pasty state times (t p ), setting (t f ), and work (t t ) obtained in curing acrylic formulations with eugenyl methacrylate and in the presence of zinc oxide particles.

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Abstract

La présente invention concerne des composés monomères dérivés de l'eugénol, la synthèse de polymères et de copolymères à partir des dérivés obtenus ainsi que la production de préparations acryliques autopolymérisables. Ces systèmes présentent des propriétés analgésiques et antiseptiques provenant de la molécule d'eugénol ancrée chimiquement dans les chaînes macromoléculaires. Ces préparations autopolymérisables peuvent être appliquées directement lorsqu'elles sont utilisées comme résines dentaires ou peuvent être injectées lors d'une utilisation pour traiter des fractures ostéoporotiques en chirurgie mini-invasive.
PCT/ES2007/070031 2006-02-15 2007-02-14 Monomères et polymères acryliques dérivés de l'eugénol, préparations et compositions les contenant et leurs applications biomédicales WO2007093662A1 (fr)

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ES200600347A ES2303430B1 (es) 2006-02-15 2006-02-15 Monomeros y polimeros acrilicos derivados de eugenol, formulaciones y composiciones que los contienen y sus aplicaciones biomedicas.

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2340241A1 (es) * 2008-05-21 2010-05-31 Consejo Superior De Investigaciones Cientificas (Csic) Copolimeros acrilicos hidrofilos derivados de eugenol, preparacion, caracterizacion y su uso como lentes oftalmicas.
WO2011141341A1 (fr) 2010-05-14 2011-11-17 Iberhospitex, S.A. Composés pour la synthèse de polyuréthane, de polyurée ou de polymères polyurée uréthane biostables
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WO2019030643A1 (fr) * 2017-08-07 2019-02-14 Foundation For Neglected Disease Research Compositions de dérivés d'eugénol pour le traitement de la leishmaniose viscérale

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