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    • 专利摘要:
    Sanitary product for antimicrobial treatment using photothermia. The invention relates to a system that subjected to a light is capable of killing the bacteria or fungi of the environment. More specifically, it is a system for insertion or implantation in living organisms comprising a substrate grafted with a polymer, and gold nanoparticles deposited on the surface of said substrate. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2637035A1
    申请号:ES201730591
    申请日:2017-03-31
    公开日:2017-10-10
    发明作者:Carmen Isabel ALVAREZ LORENZO；Sonia CABANA MONTENEGRO；Silvia BARBOSA FERNANDEZ；Pablo TABOADA ANTELO；Angel Concheiro Nine
    申请人:Universidade de Santiago de Compostela；
    IPC主号:
    专利说明:

    Medical device for antimicrobial treatment by phototennia
    Technical sector
    The invention relates to a material for destroying microorganism s. More specifically, it refers to a material with a photothermal effect that is capable of killing microorganisms of its surface or its surroundings.
    Background of the invention
    The polymeric components of medical devices that are used as inserts or implants are easily colonized by microorganisms, creating a source of infection.
    10 from which they can migrate to other parts of the body. In addition, these microorganisms that colonize said medical devices can form a biofilm that acts as a barrier to obvious antirnicl agents and favors the appearance of antibiotic-resistant microorganisms. Thus, work has been done on the development of medical devices that incorporate a technology that incorporates eliminate microorganisms that could colonize them.
    15 A very recent strategy is the coating of polymeric components with nanostructures (of adequate size and shape) of gold, which when irradiated with a frequency radiation in the near-infrared region undergo local heating capable of killing microorganisms. Khantamat et al. (AppI.Mat.Interf. 7 (2015) 39813993), have described the irradiation of nanospheres attached to the surface of a catheter
    20 model as a method to kill the EllterococclIs Jaecafis bacteria. However, in order to anchor the nanospheres to the surface of the catheter, it was necessary the previous functionalization of the gold nanoparticles with organic sulfur-containing ligands, and the previous functionalization of the substrate employed, polydimethylsiloxane, with chains having tenninal amino groups. And then through a chemical reaction they anchored
    25 covalently modified gold nanoparticles to the modified substrate. The preparation of this model catheter requires several stages of functionalization and subsequent chemical reaction, which lengthens and makes the process more complex. In addition, after irradiating 10 minutes, an average temperature of 73 ° C was reached, which is very high if this product is intended to be used as an implantable medical device.
    It should be noted that in other investigations in which a multilayer prepared by the layer-to-layer deposition technique of poly (allylamine hydrochloride), poly (f1uorescein isocyanate allylamine hydrochloride) and
    poly (4-styrenesulfonate sodium), interspersing layers of preformed gold nanoparticles, the temperature increase after irradiation of this material is high and not controllable, even forming water vapor bubbles when the material is in an aqueous medium (Adv. Funct. Mater. 22 (2012) 294-303). These results make it impossible to use this material as an implantable medical device.
    Abdou Mohamed et al. (Biomaterials 97 (2016) 154-163) use a combination of a thermosensitive and biocompatible polymer with gold nanobars (l1al1orods) to kill Gram-positive and Gram-negative bacteria. The gold nanobars were prepared by a modification with cetyl trimethylammonium bromide (CTAB) and coated with polyethylene glycol to avoid the toxic effects of the ammonium compound used. In addition to the use of CTAB, the final product has the disadvantage that when irradiated to kill bacteria there is a temperature increase of up to 25 ° C, which is very high taking into account a baseline temperature of 36 ° C. In addition, the high temperature increase changes the shape of the nanobars preventing the reuse of the system due to the release of the plasmonic band.
    According to what has been described, it is still necessary to develop suitable materials to be used as components of medical devices that, due to radiation, experience a controlled temperature increase that allows the elimination of microorganisms without causing damage to the personnel who use it or to the person or animal in which the medical device is placed / inserted / implanted, so that the material can be prepared by a simple method, avoiding toxic components and that the temperature increase is regulated precisely.
    Brief Description of the Invention
    The howls of the present invention have described "Ollado a suitable product to be used as a medical device in photogenic therapy. More specifically, they have developed a suitable system to be placed, inserted or implanted in a
    living organism, which when irradiated with light increases the temperature of its surface andmedium in which it is found and the heat released is capable of killing microorganisms, such asbacteria and fungi The system has the advantage that by irradiating, the increase intemperature is controlled and is also suitable not to cause burns or5 discomforts in the organism in which it is inserted or implanted. The increase oftemperature that has been detected for the systems of the invention is below 10 ° C (seeexample 4). Thus, an additional advantage of the invention is that the moderate increase in
    the temperature causes the nano particles to not deteriorate, so that it is possible to use the system of the invention in subsequent irradiations.
    Thus, a first aspect of the invention relates to a system for placement, insertion or implantation in living organisms comprising a substrate grafted with a polymer, and
    Gold nanoparticles on the surface of said substrate.
    A second aspect of the invention relates to a process for preparing the systems of the invention.
    A third aspect of the invention relates to a medical device comprising the system of the invention.
    A fourth aspect of the invention relates to the use of the systems of the invention as antibacterial or antifungal.
    20 Description of the figures
    Figure 1. Dependence of the percentage of acrylic acid graft (AAc) on the silicone rubber film (SR) as a function of (a) the temperature for an absorbed dose of 40 kGy, a monomer concentration of SO% v / v in toluene and 180 minutes of reaction time; (b) absorbed dose at 60 ° C, 180 minutes of reaction and a concentration of the monomer of SO% v / v in tollene; (c) reaction time for a dose of 40 kGy, a monomer concentration of 50% v / v in toluene at 60 ° C; and (d) concentration of
    monomer for a dose of 40 kGy, a concentration of the monomer of 50% v / v in toluene and 180 minutes of reaction at 60 ° C.
    Figure 2. Photographs of SR and SR-g-AAc films with 38% and 61% graft after
    of a) stirring at 10mM HAuC "for 18h at 20'C, followed by b) adding 20mM NaBH4 and washing with water; and c) stirring at 10mM HAuCk for 18h at 60 ° C, followed by d) adding 20rnM NaBH4 and water wash.
    5 Figure 3. Record of the temperature increase a) in a nanoparticle dispersionof gold and b) in films of SR and SR-g-AAc grafted at 14% and 38% before (symbolsempty) and after the immobilization of gold nanoparticles (full symbols) duringirradiation with a 514 nm laser (0.5W / cm2).
    Figure 4. Colony formation units (CFU) of SlaphylococclIs oureus attached to
    10 SR and SR-g-AAc films with and without gold nanoparticles immobilized on the surface (prepared according to example 3).
    Figure 5. UV-Vis spectrum of gold nanoparticles prepared in Example 2, gold nanoparticles released from the SR-g-AAc film with 38% grafting to the aqueous medium and an SR-g-AAc film with 38% graft with nano gold particles
    15 fixed assets, after autoclaving.
    Detailed description of the invention
    A first aspect of the invention relates to a system for placement, insertion or implantation in living organisms comprising a substrate grafted with a polymer, and 20 gold nanoparticles on the surface of said substrate.
    The systems of the invention are suitable to be placed, inserted or implanted in living beings. Thus, all materials that are incompatible with this particular use are excluded from the invention, such as glass.
    "Substrate" means that which serves as a seat for the other components of the
    25 system In a particular embodiment, the substrate used in the systems of the invention is selected from silicone rubber, polyurethane, polypropylene, polyethylene, polyethylene terephthalate, polyvinyl chloride, nylon, cellulose acetate, polylactic acid, poly (Lactic acid). -co-glycolic), and polyurethane.
    In the system of the invention, the substrate is grafted with a polymer. For purposes of the invention, the grafted polymer is a biocompatible polymer. Forthe
    S In a particular embodiment, the grafted polymer in the substrate is selected from polyacrylic acid, polymethacrylic acid, cross-linked citric acid, carboxymethyl cellulose, dextran sulfate, agar agar, polylactic acid, poly (lactic-co-glycolic acid), derived polymers of maleic acid, poly (4-hydroxybenzoic acid), poly (3-hidoxybutyric acid), poly (itaconic acid), and poly (styrenesulfonic acid).
    10 The percentage of polymer grafting on the substrate may vary depending on the conditions used in the process. A suitable percentage for the purposes of the invention is between 8% and 120%, more preferably between 13% and 100%, more preferably between 10% and 65%. Bearing in mind that when the material has a higher graft degree, less nanoparticles are deposited, then a preferred embodiment of the invention is between 10% and 45%.
    fifteen The system of the invention that comprises a substrate with a polymer also comprises gold nanoparticles that are deposited on its surface.grafted,
    twenty Surprisingly, the previously prepared gold nanoparticles were not deposited on the substrate after a period of incubation, as shown in example 2. Only when the gold nanoparticles were prepared in situ in the presence of the grafted substrate was the coating feasible of the substrate. Furthermore, said gold nanoparticles thus prepared are not modified or coated by any substance.
    The gold nanoparticles deposited on the substrate have an average size of between 500 nm and 1 nm, preferably between 100 nm and 1 nm, more preferably between 50 nm and 1 nm, even more preferably between 35 nm and 1 nm.
    25 In a particular embodiment, the system of the invention comprises a silicon rubber grafted with a bioeompatible polymer, and gold nanoparticles deposited on the surface, with an average nanoparticle size between 500 nm and I nm, preferably between 100 nm and l nm.
    In another particular embodiment, the system of the invention comprises a substrate as previously grafted with poly acrylic acid, and gold nano particles.
    deposited on the surface, with an average nanoparticle size between 500 nm and 1 nm, preferably between 100 nm and 1 nm.
    In another particular embodiment, the system of the invention comprises a silicone rubbergrafted with polyacrylic acid, and gold nanoparticles deposited on the surface, with5 an average size of the nanoparticles between 500 nm and 1 nm, preferably between 100nrn and 1 nm.
    In another particular embodiment, the system of the invention comprises a silicone rubber grafted with polyacrylic acid with a graft percentage of between 8% and 120%, and gold nanoparticles deposited on the surface, with an average size of the
    10 nanoparticles between 500 nm and 1 nm, preferably between 100 nm and 1 nm.
    In another particular embodiment, the system of the invention comprises a silicone rubber grafted with polyacrylic acid with a graft percentage of between 10% and 65%, and gold nanoparticles deposited on the surface, with an average size of the nanoparticles between 500 nm and 1 nm, preferably between 100 nm and I nm.
    In a second aspect, the invention relates to a process for preparing the system of the invention as described above, comprising:
    a) contacting a grafted substrate with a polymer with auric chlorine acid
    or a gold salt in aqueous medium, 20 b) optionally add a reducer.
    Surprisingly, gold nanoparticles are formed during stage a) of the spontaneous fonna procedure, as shown in example 3. Although if you are looking for a larger deposit of nanoparticles you can also choose to perform stage b). After stage b) the amount of gold nanoparticles deposited is higher than in stage
    25 a).
    The process of the invention has the advantage that nanoparticles are formed directly on the substrate, it is not necessary to pre-pre-order or modify them.
    This makes the process of the invention simple and proceeds in a single step.
    Step a) takes place under stirring at a temperature between 15 and 70 ° C, preferably between 15 and 60 ° C. The spontaneous deposition that occurs at this stage is higher when the temperature is between 15 and 30 ° C, more preferably at 20 ° C.
    The graft degree of the substrate can vary between 8% and 120%, more preferably between 13% and 100%, more preferably between 10% and 65%. Taking into account that when the material has a lower degree of grafting, more nanoparticles are deposited, then a preferred embodiment of the invention is between 10% and 45%.
    In step b) a reduction of the gold compound occurs and nanoparticles are formed massively deposited in the grafted substrate. The reducer will be a usual reducer in the chemical industry such as sodium borohydride, aluminum lithium hydride, sodium or potassium thiosulfite, sodium citrate. Preferably the reaction proceeds under mild conditions. Preferably, the reductant is sodium borohydride.
    The process may further include an intermediate step between stage a) and stage b) in which the aqueous medium is removed and water is added.
    In a further aspect, the invention is directed to a system obtainable by the method described above.
    In a third aspect, the invention is directed to a medical device comprising a system as described above.
    "Health product" means a device used in healthcare that is regulated by health regulations, such as surgical implants, ophthalmological implants, osteoarticular implants, patches, dressings, catheters, probes, bandages, bags, canalization systems for administration of medications, systems
    25 channeling of biological fluids, dressings, tubes, sutures, or prostheses.
    In a particular embodiment, the invention relates to surgical implants, ophthalmological implants, osteoarticular implants, patches, apos, catheters, probes, bandages, bags, canalization systems for medication administration, biological fluid channeling systems, dressings, tubes , sutures, or prostheses that comprise the
    system of the invention as described above.
    A fourth aspect of the invention refers to the systems of the invention as they have been
    described above, and to the medical device, for use as an antibacterial or5 antifungal.
    Another embodiment of the invention relates to a method for destroying microorganisms comprising exposing to radiation a system in contact with bacteria or fungi, said system comprising a substrate grafted with a polymer, and
    Gold nanoparticles deposited on the surface of said substrate, as described above, or a medical device as described above.
    In a particular embodiment, the radiation has a wavelength between 450 nm and 1000 nm, preferably between 500 and 900 nm.
    The following examples should be interpreted as illustrative of the invention and not as limiting thereof. Example 1. Preparation of grafts of polyacrylic acid (PAAc) in silicone films
    (SR-g-AAc).Materials employedThe silicone rubber (SR) film was supplied by Goodfellow (Huntingdon,
    20 United Kingdom), cut into 2.5 cm x 1 cm portions and washed with ethanol for 3 h three times before drying at 50 ° C under vacuum. Acrylic acid (AAc), boric acid, sodium citrate dihydrate, tribasic sodium phosphate dodecahydrate, tetrachlorouric acid
    (lll) (HAuCL,) and sodium borohydride (NaBH4) were supplied by Sigma Aldrich (St Louis, MO, USA). AAc was distilled under reduced pressure before use. Toluene, monobasic potassium phosphate and sodium hydroxide were from 8aker (Mexico). Distilled water was used in all experiments.
    The SR films were irradiated in air using a GOCo gamma radiation source (Gammabeam 65 1 PT, Nordion Inc. Callada, installed at the Institute of Nuclear Sciences 30 of UNAM, Mexico) at a dose rate of 9.9 kGy / h. After the
    irradiation, the films were introduced in glass ampoules containing AAc solutions in toluene (concentrations in Table 1). The oxygen was then removed by cooling the blisters for 15 minutes by immersion in liquid nitrogen and applying
    vacuum to remove air. This process was repeated four times. The ampoules were sealed and heated under different conditions (Table 1) to fomulate the graft copolymer. After the reaction, the films were washed in ethanol three times (replacing the medium every 12 h) and dried in vacuo. The percentage of graft was calculated as follows:
    Wg
    Graft (%) = --Wo · 100 Eq. (one)
    w,
    Where Wo and Wg represent the mass of the films before and after grafting,
    10 respectively. Table 1. Experimental conditions for grafting acrylic acid (AAc) into SR films by the pre-irradiation method.
    Evaluation parameter DoseAAcinI fear peratureWeatherfrom
    (kGy) Toluene(%r C)reaction
    vlv) (min)
    Dose 20-100fifty60180
    Temperature 40fifty50-80180
    Reaction time 40fifty6030-180
    Monomer concentration from4030-8060180
    At 50 ° C or at lower temperatures it was not possible to graft the SR films, but at 60 ° C
    15 the percentage of grafting was significant. At temperatures above 60 ° C the percentage of grafting was extremely high, exceeding 200%, but material deterioration occurred. The percentage of grafting on the SR film depends on the dose of radiation previously absorbed. In a dose range of 20 to 60 kG and graft percentages of up to
    20 100% For a fixed dose of 40 kG and the graft range is between 8% and 65%, at times of 8 and 180 minutes respectively. By varying the concentration of monomers between 30 to 80% v / v, the percentage of grafting varies between 13 and 120%.
    SR, PAAc and SR-g-AAc films were characterized by Fourier transform infrared spectroscopy (FT-IR) using a PerkinElmer Spectrum 100 spectrometer (PerkinElmer Cetus lnstruments, Norwalk, CT). For the SR-g-AAc grafted films, characteristic signals of the SR film and the PAAc polymer were observed, the band being
    5 corresponding to group C = O more intense the higher the percentage of grafting. Thermogravimetric analysis (TGA) and differential scanning calorimetry analysis (DSC) confined the grafting of PAAc on the SR film The thermogravimetric analysis was carried out on a TGA Q50 (TA Instruments, New Castle, DE) heating equipment. at SOO ° C at IO ° C / min under nitrogen atmosphere. Scanning calorimetry analyzes
    10 differential (DSC) were recorded using an OSC 20 I O calorimeter (T A lnstruments, New CaSI le, DE) between 25 and 300 ° C at 10 ° C / rnin. The pH response capacity of the grafted copolymers was evaluated by measuring the degree of swelling in aqueous medium at pH between 2 and 10 for S h. The swollen copolymer films were weighed after drying their surface with foil.
    15 fi lter to eliminate free water. The swelling percentages were quantified as follows: Swelling (%) == Ws-Wd .100 Eq. 2
    W
    In this equation Wd and Ws represent, respectively, the mass of the dry film and the swollen film. The SR film does not swell in water due to its hydrophobic nature.
    20 Materials with 3 different graft percentages were evaluated and different degrees of swelling were observed in each of them, the critical pH being 4.5. The mechanical properties were also evaluated, recording the storage (G ') and loss (G ") modules of SR and SR-g-AAc films on a Rheolyst AR 1000N rheometer (TA lnstruments, New Castle, DE) equipped with a torsion kit
    25 solid and a data analyzer (AR2500). The films were analyzed in duplicate at 20 oC in the angular frequency range of 0.05-50 rad / s with 0.5% deformation. SR-g-AAc films with a graft grade of 14% maintained the viscoelastic parameters of SR with G 'and G "values of 2.4' 106 and IS · 105 Pa, respectively. When the graft grade was 3S%, obtained G 'values of 7.6' 106 Pa and G "of
    30 3.0 '105 Pa, while when the graft was 61% the values of G' and G "were
    17. S · 1 06 and 5.9 '105 Pa, respectively.
    Example 2. Immobilization of gold nanoparticles in basic medium. Citrate-protected gold nanoparticles (AuNPs) were prepared by adding sodium citrate (10 mg / ml, 2.5 ml) to a solution of HAuCL (0.5 mM, 50 ml) with stirring
    continuous at 100 ° C for 15 min. Upon cooling, gold nanoparticles with a size of about 10-15 nm in diameter and with a plasma band centered at 520 run were obtained. Next, a method previously described by Jans et al. (H. Jans, K. Jans,
    L. Lagae, G. Borghs, G. Maes, Q. Huo, Poly (acrylic acid) -stabilized colloidal gold nanoparticles: synthesis and properties, Nanotechnol. 21 (2010) 455702) for coating AuNPs with PAAc with some modifications. The SR-g-AAc films were cut into 8 mm diameter discs and kept separately (3 replicates) for 3 h at 20 oC in vials with I mL of the AuNPs dispersion (463 f.1M) and 40 J1L of NaOH (0.5 M). After 3 h under magnetic stirring (250 rpm), 40 ~ NaOH (0.5 M) was added. The vials were kept under agitation for another 18 h. After removing the medium, the films were washed with plenty of water for 24 h, replacing the water three times. However, after this incubation time, the gold nanoparticles were not immobilized in the SR-g-AAc film.
    Example 3. Immobilization of gold nanoparticles in a reducing medium. SR or SR-g-AAc films with 14.38 and 61% graft (8 mm diameter discs) were immersed in 2 ml of HAuC4 (10 mM) and kept for 24 h under magnetic stirring (250 rpm) at 20 oC or 60 oc. A color change was observed, indicating the spontaneous deposition of gold nanoparticles after a few minutes at both 20 ° C and 60 ° C. Although the color change was more intense at 20 ° C (Figures 2a and 2c). Then, the medium was carefully removed, the films were transferred to new vials and Na8H4 solution (2 ml, 20 mM, freshly prepared in cold water) was added to the films and the remaining HAuClt solution. All vials were kept under agitation for another 15 minutes. Finally, the films were washed with plenty of water for 24 h, replacing the water three times. In all cases, at least four independent replicates were tested. A more intense color change to violet was observed, indicating a massive reduction of gold and a greater deposition of the nanoparticles on the films. It was vigorously stirred and the color was not attenuated, demonstrating that the nano particles are associated with grafted films.
    The deposition of the gold nanoparticles was greater the lower the graft grade, and thus for a graft grade between 14% and 38% the color was more intense than when the graft grade was 6 1% (Figures 2b and 2d).
    On the other hand, after adding Na8H4 to the excess HAuCl, under the same conditions as on the film, nanoparticles were obtained which were analyzed using a Philips CM-12 transmission electron microscope (TEM) (FEI Company, The Netherlands). The size of these nanoparticles was between 10 and 20 nm, which should be similar to the nanoparticles fused in situ on the grafted substrate. The prepared films were visualized with three magnifications (I000x, 3000x and 10000x) in an EVO-LS 15 device (Zeiss, Germany) coupled with an X-ray energy dispersion spectrometry accessory (EDX). In some cases, in order to perform this analysis, the samples were subjected to plasma ablation (Plasma Cleaner FISCHIONE Model 1020, Denmark) for 10 minutes to remove the graft and make possible a detailed visualization of the deposited gold nanoparticles. And so the presence of gold nanoparticles on the surface of the films was confirmed, being more abundant when the process was carried out at 20 ° C. The SR and SR-g-AAc 14% and 38% graft films showed high physical stability and resistance to autoclave and ultrasound treatment with a lower release of gold nanoparticles. The discs did not lose the violet color after these treatments.
    Example 4. Answer fototénni ca. The photothermal responsiveness of preformed AuNPs was evaluated using a 514 nm laser (Changchun New Industries Optoelectronics Technology, China) radiating aqueous dispersions of AuNPs (2 mL, 9.26 to 463 JlM) at room temperature with a spot of 0 , 37 cm2 at a power density of 0.5 W / cm2 for 20 minutes. The AuNPs dispersions were maintained at a distance of 5.5 cm from the laser under magnetic agitation. SR and SR-g-AAc 14% and 38% graft films (8 mm diameter discs) without further modification and after immobilization of gold (obtained according to example 3) were irradiated at room temperature with a 514 laser nm (Changchun New Industries Optoelectronics Technology, China) with a spot size of 0.37 cm2 at a power density of 0.5 W / cm2 for 20 min. Samples were kept at a distance of 5.5 cm from the laser. The temperature rise was recorded with a K type thermocouple and a multimeter (Keithley 2000, USA). The experiments were performed in triplicate.
    The gold nanoparticles in solution experienced a temperature increase that
    5 is dependent on the concentration of nanoparticles in aqueous dispersion. Thus, the highest concentrations experienced a temperature increase of 1.3 ° C after irradiating 5 minutes, and 2.5 ° C after 20 minutes of irradiation (Figure 3a). In the case of SR-g-AAc films, the temperature increase was greater due to the higher density of gold nanoparticles. After 5 minutes of irradiation the
    The temperature was increased between 6 and 7 ° C when SR-g-AAc films were used with 14% and 38% grafting and immobilizing gold nanoparticles (Figure 3b). When gold nanoparticles were formed on SR films without grafting, the temperature increase was limited to 3.5-4 ° C.
    15 Example s. Antimicrobial activity Discs (8 mm in diameter) of 14% SR and SR-g-AAc films and 38% graft without further modification and with immobilized AuNPs, prepared according to Example 3 at 20 ° C, were immersed separately in 2 mL of Tryticase soybean culture medium (TSC) inoculated with 3.6x109 CFU / ml of StaphylococclIs aureus ATCC 25923 and incubated
    20 for 2 h at 3rc. Four discs of each material were tested. After incubation, the discs were washed with water and two of them were irradiated for 5 min with a laser of 5 14 nm at a power density of 0.5 W / cm2 • Then, both the irradiated and non-irradiated discs they were placed in a vial containing 2 mL of PBS (pH 7.4) and sonicated for 1 min. Dilutions of each medium were prepared and brought to
    25 tripticase soy agar plates (TSA). Plates were incubated at 37 ° C for 24 h and colonies were counted. It was found that the presence of immobilized gold nanoparticles in the films did not prevent adhesion and proliferation. However, irradiation of the films led to a significant reduction of bacteria (Figure 4). No effect of the
    30 SR films that did not have gold nanoparticles. These results continue the death of bacteria induced by phototennia due to a rapid conversion of light into thermal energy. The film with greater efficiency was the grafted to 14% probably by a
    higher gold particle density.
    Example 6. Autoclave
    5 The films SR and SR-g-AAc 14% and 38% graft with immobilized gold and previouslyused for antimicrobial tests underwent a sterilization cycle bymoist heat in autoclave (121 ° C, 30 min, Trade Raypa AES-12, Spain) separatelyin vials containing 2 mL of water. After autoclaving the absorbance of the medium isrecorded using a UV-vis spectrophotometer (Agilent 8453, Germany).
    10 Plasmon resonance spectra were recorded using a UVvis photometer spectrum (Agilent 8453, Germany).
    The gold nanoparticles prepared in Example 2 and the nanoparticles released from the substrate showed a similar plasma profile (Figure 5).
    权利要求:
    Claims (11)
    [1]
     Claims
    l. System for placement, insertion or implantation in living beings comprising a substrate grafted with a polymer, and gold nanoparticles on the surface of said substrate.
    S 2. System according to claim I wherein the substrate is selected from silicone rubber, polyurethane, polypropylene, polyethylene, polyethylene terephthalate, polyvinyl chloride, nylon, cellulose acetate, polylactic acid, poly (lactic-coglycolic acid), and polyurethane.
    [3]
    3. System according to claim 1, wherein the polymer is selected from among
    10 polyacrylic, polymethacrylic acid, cross-linked citric acid, carboxymethyl cellulose, dextran sulfate, agar agar, polylactic acid, poly (lactic-co-glycolic acid), polymers derived from maleic acid, poly (4-hydroxybenzoic acid), poly acid (3-hydroxybutyric acid), poly (itaconic acid), and poly (styrenesulfonic acid).
    [4]
    4. System according to any of the preceding claims, wherein
    15 gold nanoparticles have an average size between 500 nm and I nm, preferably between 100 nm and I nm, more preferably between 50 nm and I nm, even more preferably between 35 nm and I nm.
    [5]
    5. System according to any of the preceding claims, comprising a silicone rubber grafted with a biocompatible polymer, and gold nanoparticles
    20 deposited on the surface, with an average nanoparticle size between 500 nm and 1 nm.
    [6]
    6. System according to any of the preceding claims, comprising a substrate grafted with polyacrylic acid, and gold nanoparticles deposited on the surface, with an average size of nanoparticles between 500 nm and I nOl.
    System according to any one of the preceding claims, comprising a silicone rubber grafted with polyacrylic acid, and gold nanoparticles deposited on the surface, with an average size of the nanoparticles between 500 nm and 1 nm.
    [8]
    8. System according to any of the preceding claims, comprising a
    30 silicone rubber grafted with polyacrylic acid with a graft percentage of between 8% and 120%, and gold nanoparticles deposited on the surface, with an average size of nanoparticles between 500 nm and 1 nm.
    [9]
    9. Procedure forpreparehesystemdescribedintherei vindicationone,that
    understands:
    to) contacting a grafted substrate with a polymer with auric chlorine acid
    or a golden salt in aqueous medium,
    s b)optionally add a reducer.
    [10]
    10. Procedure accordingtheclaim9 whereinthestage a)themixturebe
    maintains between 15 ° C and 70 ° C.
    [11]
    11. Method according to claim 9, wherein between stage a) and stage b)
    Remove the aqueous medium and add water.
    10 12. System obtainable by the method described according to claim 9.
    [13]
    13. Product sanitarythatunderstandsasystemaccordinganyonefromthe
    claims 1-8, and 12.
    [14]
    14. Implants surgicalimplantsophthalmologic,implantsosteoarticular,
    patches, dressings, catheters, probes, bandages, bowls, canalization systems for
    lS medication administration, biological fluid channeling systems,
    dressings, tubes, sutures, or prostheses comprising the system according to any of
    claims 1-8, and 12.
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    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    CN102286185A|2011-06-29|2011-12-21|天津大学|Temperature sensitive composite gold nano particles and preparation method and catalytic application thereof|
    US20160067354A1|2014-08-29|2016-03-10|University Of South Carolina|Preparations of gold/mesoporous silica hybrid nanoparitcle and applications|
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