CN100596332C - Medicine-carrying contact lens and preparation method thereof - Google Patents
Medicine-carrying contact lens and preparation method thereof Download PDFInfo
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- CN100596332C CN100596332C CN200810021962A CN200810021962A CN100596332C CN 100596332 C CN100596332 C CN 100596332C CN 200810021962 A CN200810021962 A CN 200810021962A CN 200810021962 A CN200810021962 A CN 200810021962A CN 100596332 C CN100596332 C CN 100596332C
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Abstract
The invention relates to a drug-loaded contact lenses and a corresponding preparation method. The drug-loaded contact lenses are obtained firstly through UV-curing or heat-curing and then through drug-liquid immersion. The drug-loaded contact lenses can be particularly defined as a combination of a contact lenses material containing cyclodextrin and drug molecules and comprise the contact lenses formed by combining a crosslinked polymer hydrogel formed by copolymerizing mono-substituted cyclodextrin monomers, polymerization monomers and crosslinkers with one kind or a plurality of acetazolamide, methazolamide, puerarin or prostaglandin. The characteristic of forming inclusion compounds between the cyclodextrin molecules and drug molecules is adopted to increase the quantity of loaded drugsso as to reduce the stimulation to eyes by drugs and control the drug release speed for eye diseases of curing glaucoma, etc.
Description
Technical field
The present invention relates to a kind of medicine carrying contact lenses and preparation method thereof, it is characterized in that cause solidifying by ultraviolet light or heat and obtain, the immersion by soup obtains the medicine carrying contact lenses.Specifically, in the present invention single substituted cyclodextrin molecule is introduced in the contact lens material, utilize cyclodextrin molecular can and drug molecule between form the characteristic of inclusion compound, increase drug loading, the release rate of control medicine.Be specially adapted to lipophilic drugs, have the dosing eyes of the medicine of irritating medicine of strong eye and poor stability, be used for the treatment of eye diseases such as glaucoma.
Background technology
Soft contact lens mainly is divided into hydrophilic contact lens and high oxygen flow contact lenses at present.Hydrophilic contact lens mainly is as bulk material with polymethylacrylic acid-2-hydroxyl ethyl ester (PHEMA), in order to improve the water cut of material, improve the performance of material, in the PHEMA material, introduce hydrophilic monomers such as N-vinyl pyrrolidone (NVP) or methacrylic acid.High oxygen flow contact lens material is the silicone-hydrogel material, and it has high oxygen permeability coefficient, is suitable for wearing continuously.
Cyclodextrin be a class by the cyclic oligomer sugar compounds that glucose molecule links, have the lipophilicity hole of hollow, molecular surface has a plurality of hydroxyls.The research of cyclodextrin at present mainly concentrates on three directions: 1) be that cyclodextrin and other reagent carry out the synthetic cyclodextrin of polycondensation reaction; 2) introduce unsaturated link in the cyclodextrin molecular, be prepared into polymerisable vinyl monomer, and then cause the formation homopolymerization or prepare cyclodextrin with other monomer copolymerizations; 3) cyclodextrin is immobilized on macromolecular scaffold.
Because contain a large amount of hydroxyls in the cyclodextrin molecular, so less about the relevant report of vinyl cyclodextrin monomer, the research of particularly mono-substituted vinyl cyclodextrin monomer seldom.Representative mono-substituted vinyl cyclodextrin monomer mainly contains following synthetic route:
People (Harada such as Harada A, Furue M, Nozakum S.Cyclodextrin-containingpolymers.1.Preparation of polymers.Macromolecules, 1976,9:701-704) reported a kind of preparation method of single substituted ethylene basic ring dextrin monomer as far back as 1976, he at first uses metanitrophenol the acryloyl chloride esterification, utilize metanitrophenol and cyclodextrin formation inclusion compound then and ester exchange reaction takes place, successfully synthesize single substituted ethylene basic ring dextrin monomer. (Synthesis andCharacterization of β-Cyclodextrin Based Functional Monomers and itsCopolymers with N-isopropylacrylamide.Macromol.Biosci.2003 such as Liu Yuyang, 3,715-719.) utilize same principle, also synthesized single substituted ethylene basic ring dextrin monomer through three-step reaction.
Diester and cyclodextrin that Dirk vetter etc. discloses in patent US005488102A with both-end position vinyl react; successfully prepared single substituted ethylene basic ring dextrin monomer .Stephenhannessian that two kinds of ester bonds connect etc. and in patent US005959089A, disclose the mono-substituted cyclodextrin monomer of allyl ether, equally compound has been protected.
There is the pertinent literature report that cyclodextrine derivatives is introduced in the contact lens material at present.
Patent US005391592A derives to the hydroxylic moiety of cyclodextrin and is unsaturated double-bond, utilizes the addition reaction of si-h bond and two keys then, cyclodextrin molecular is incorporated in the silastic material, as contact lens material.Utilize polyhydric water wettability in the cyclodextrin molecular, increase the water wettability of material.
Patent WO96/13511 discloses in contact lens material polymerization and has gone into carbohydrates such as cyclodextrin, but the unsaturated cyclodextrine derivatives for preparing in this patent is to contain two or more than two polymerisable unsaturated group, uses as crosslinking chemical with it.
Jap.P. JP3475252 has prepared the linear cyclodextrin polymkeric substance with cyclodextrin and PEG. and patent EP1852454A1 has introduced acrylic acid groups on the basis of this linear polymer, obtain photo curable cyclodextrin macromonomer, prepares hydrogel material.
The application of cyclodextrin in the dosing eyes system starts from the nineties in 20th century.Thereby cyclodextrin molecular can form the physicochemical property that inclusion changes medicine with multiple medicine, as increase the solubleness of fat-soluble medicine and stability, the bioavailability of medicament that improves, the pungency etc. that reduces, therefore, cyclodextrin is subject to people's attention day by day in the application of dosing eyes system, has been widely used as excipient substance at present. the high hydroxypropyls of water-soluble that use in ophthalmic remedy more.
Mostly the application of cyclodextrin in ophthalmic remedy at present is the preparation eye drops, as US2007149480-A1, WO2007012974-A2, US2006258617-A1 etc., cyclodextrin molecular (being generally the bigger hydroxypropyl of solubleness in the water) is joined in the eye drops as auxiliary material. utilize the inclusion character of cyclodextrin to improve the physicochemical property of medicine, or improving the formulation shortcoming. the ophthalmic medicine that wherein relates to has multiple, as: acetazolamide, PILO, cyclosporine, dexamethasone, Dipivefrine, prostaglandin etc.
The main formulation of ophthalmic remedy is eye drops or spongaion, run off easily at eye in order to overcome eye drops, the spongaion formulation shortcoming of the tolerance difference that causes such as affect one's power of vision, developed gel-type preparation, intraocular implant and medicine carrying contact lenses, contact lenses are used for medicine carrying and treat the existing relevant report of eye disease.
Derya Gulsen (Anuj Chauhan, Dispersion of microemulsion drops in HEMAhydrogel:a potential ophthalmic drug delivery vehicle.Int J Pharm2005; 292 (1-2): 95-117.) wait and in contact lens material, to load nanoparticle or liposome, utilize wherein nanoparticle or liposome to carry out medicine carrying; Uchida R (Uchida R, Sato T, Tanigawa H, Uno K.Azulene incorporation and release by hydrogel containing methacrylamidepropyltrimenthylammonium chloride, and its application to soft contactlens.J Controlled Release 2003; 92 (3): 259-64.) grade has prepared the ion-type hydrogel material, and the electrostatic attraction of using positive and negative charge improves the adhesion of ionic drug in material; Hiratani H (Hiratani H, Alvarez-Lorenzo C.The nature of backbone monomersdetermines the performance of imprinted soft contact lenses as timololdrug delivery systems.Biomaterials 2003; 25 (6): 1105-13.) wait, slow down the release rate of medicine with molecular engram method increase drug loading; Siddarth Venkatesh (SiddarthVenkatesh, Stephen P.Sizemore, et al, Biomimetic hydrogels for enhancedloading and extended release of ocular therapeutics, Biomaterials 28 (2007) 717-724) specific binding capacity of analog antibody and antigen such as has prepared the hydrogel of biomimetic type.
What this patent related to is a kind of medicine carrying contact lenses and preparation method thereof, be different from existing contact lenses and medicine-carrying method thereof, it is characterized in that single substituted ethylene basic ring dextrin monomer covalency of high-load is aggregated in the cross-linked polymer hydrogel contact lens binding site as medicine, the preparation method is a polymerization single polymerization monomer, crosslinking chemical and cyclodextrin monomer mix, add initiating agent, ultraviolet light or heat cause curing and obtain the macromolecule network hydrogel, and medicine carrying is finished by soaking in certain density soup.This medicine carrying contact lenses can prolong drug action time, bioavilability is provided, be used for the treatment of eye diseases such as glaucoma.
Summary of the invention
Technical matters: the purpose of this invention is to provide a kind of medicine carrying contact lenses and preparation method thereof.
Technical scheme: the present invention relates to a kind of medicine carrying contact lenses and preparation method thereof, different with the preparation method of in the past medicine carrying contact lenses, this medicine carrying contact lenses are single substituted cyclodextrin molecules of introducing high-load in contact lens material, utilize cyclodextrin molecular can form the characteristics of clathration with drug molecule, increase the affinity of contact lenses to drug molecule, increase drug loading, and the release rate of control medicine.
The present invention relates to the medicine carrying contact lenses, comprise one or more contact lenses that combine in cross-linked polymer hydrogel that single substituted cyclodextrin monomer, polymerization single polymerization monomer, crosslinking chemical copolymerization obtain and acetazolamide, methazolamide, Puerarin or the prostaglandin.
Described single substituted cyclodextrin monomer is:
, wherein:
Be alpha-cyclodextrin or beta-schardinger dextrin-or gamma-cyclodextrin; A is N or 0 heteroatoms, R
1For alkyl or contain N, the hydrocarbon of O atom, R
2Be methyl or H.
Described polymerization single polymerization monomer is: 2-hydroxyethyl methacry-late, the N-vinyl pyrrolidone, (methyl) methyl acrylate or (methyl) ethyl acrylate, (methyl) acrylic acid, the N-vinylamide, DMAA, 3-methacryloxypropyl three (trimethylsiloxy) silane, the big monomer of organosilicon, the potpourri of wherein one or more.
Described crosslinking chemical is: two or three (methyl) acrylic acid multielement alcohol ester.The big monomer of organosilicon is:
R wherein
1Be methyl or hydrogen; R
2, R
3, R
4, R
5Be C
1～C
12Alkyl or trimethylsiloxane group group; X is-NHCOO-or-OOCNH-R-NHCOO-, wherein R is C
4～C
13Alkyl; A, c are that 1～20 integer, d are that 2～30 integer, b are 0～20 integer; Y is the combination of following structure 1 and structure 2,
Wherein structural units is 0.1～10 than e/f; R
6, R
7Be C
1～C
12Hydrocarbon group or fluorine-containing C
1～C
12Hydrocarbon group, R
8, R
9For hydrocarbon group or contain the hydrocarbon group of oxygen atom.
The preparation method of medicine carrying contact lenses: polymerization single polymerization monomer, crosslinking chemical, single substituted cyclodextrin monomer and initiating agent are mixed, inject mould, cause curing with ultraviolet light or heating, immerse in the solvent after the demoulding, remove unreacted monomer, obtain the cross-linked polymer hydrogel contact lens, be placed on concentration then and be in the aqueous solution of 0.01%～10% medicine and soak, described medicine is one or more in acetazolamide, methazolamide, Puerarin, prostaglandin, PILO, cyclosporine, dexamethasone, the Dipivefrine.
Described solvent is one or more in water, saline solution, isopropyl alcohol, ethanol, the phosphate buffer.
Add thinning agent when polymerization single polymerization monomer, crosslinking chemical, single substituted cyclodextrin monomer and initiating agent are mixed, described thinning agent is one or more in water, isopropyl alcohol, the n-propanol.
The medicine that loads is an ophthalmic administration, as acetazolamide, methazolamide, Puerarin, PILO, cyclosporine, dexamethasone, Dipivefrines etc. comprise above-mentioned medicine but are not subject to described medicine, feature is an ophthalmic remedy, and this ophthalmic remedy can form inclusion compound with cyclodextrin molecular.
Above mentioned cyclodextrin is an alpha-cyclodextrin, beta-schardinger dextrin-, one or more in the gamma-cyclodextrin.
Technique effect: compared to medicine carrying contact lenses of present bibliographical information and preparation method thereof, the medicine carrying contact lenses that the present invention relates to have following technological merit:
1) the medicine carrying contact lenses that the present invention relates to are the cross-linked polymer hydrogels that obtained by mono-substituted cyclodextrin monomer and polymerization single polymerization monomer, crosslinking chemical polymerization, and the cyclodextrin structure unit can stably be fixed in the cross-linked network structure.
2) cyclodextrin monomer of Jia Ruing is a mono-vinyl substituted cyclodextrin monomer, changes the addition of cyclodextrin monomer in can be in a big way, thus the drug loading of control contact lenses.
3) the medicine carrying contact lenses that the present invention relates to are that the cross-linked polymer hydrogel is immersed in the soup, drug molecule is attached in the hydrophobic cavity of cyclodextrin molecular, and by changing the concentration of soaking soup, the content of control glasses Chinese traditional medicine, simple, the easily control of preparation technology.
4) the medicine carrying contact lenses Chinese traditional medicine molecule that the present invention relates to combines with cyclodextrin, can effectively delay the release of medicine.
5) the medicine carrying contact lenses that the present invention relates to are size constancy before and after drug.
6) the medicine carrying contact lenses that the present invention relates to can the sustained release acetazolamide, methazolamide, Puerarin, PILO, cyclosporine, dexamethasone, one or more medicines such as Dipivefrine.
For the convenience of statement has adopted the statement of medicine carrying contact lenses, but its application is not limited to as the medicine carrying contact lenses, and purposes is as eye disease medicine for treatment film widely, as intraocular implant etc.
Description of drawings
Fig. 1. the drug curve of the contact lenses of load Puerarin (soak solution Puerarin concentration 0.16mg/ml)
Fig. 2. the drug curve of the contact lenses of load Puerarin (soak solution Puerarin concentration 0.802mg/ml)
Fig. 3. wear behind the medicine carrying contact lenses Puerarin concentration and time relation in the rabbit tear.Contact lenses are (A): 0.334mg/ml in Puerarin concentration in advance; (B): immersion treatment medicine carrying in the solution of 0.802mg/ml.
Fig. 4. wear behind the medicine carrying contact lenses Puerarin concentration and time relation in the rabbit aqueous humor.Contact lenses are immersion treatment medicine carrying in the solution of 0.802mg/ml in Puerarin concentration in advance.
Embodiment
The present invention relates to the medicine carrying contact lenses, it is characterized in that the medicine carrying contact lenses are cross-linked polymer hydrogels that contain cyclodextrin of specific bond drug molecule.The cross-linked polymer hydrogel is the cross-linked polymer hydrogel that contains cyclodextrin that is obtained by following monomer copolymerization.(1) mono-substituted cyclodextrin monomer:
Wherein:
Be alpha-cyclodextrin or beta-schardinger dextrin-or gamma-cyclodextrin; A is N or O heteroatoms, R
1For alkyl or contain N, the hydrocarbon of O atom, R
2Be methyl or H;
(2) polymerization single polymerization monomer: 2-hydroxyethyl methacry-late (HEMA), N-vinyl pyrrolidone (NVP), (methyl) methyl acrylate or (methyl) ethyl acrylate, (methyl) acrylic acid, N-vinylamide (VMA), DMAA (DMA), 3-methacryloxypropyl three (trimethylsiloxy) silane (TRIS), one or more in the big monomer of organosilicon; The big monomer of organosilicon is:
(3) crosslinking chemical: the polymerization system of two or three (methyl) acrylic acid multielement alcohol ester.
Drug molecule is an acetazolamide, methazolamide, and Puerarin, PILO, cyclosporine, dexamethasone, one or more in the Dipivefrine are attached in the cyclodextrin hydrophobic cavity.
The preparation method who the present invention relates to the medicine carrying contact lenses mixes polymerization single polymerization monomer, crosslinking chemical, mono-substituted cyclodextrin monomer and initiating agent, inject mould, cause curing with ultraviolet light or heating, immerse in the solvent after the demoulding, remove unreacted monomer, obtain the cross-linked polymer hydrogel contact lens, be placed on concentration then and be in the aqueous solution of 0.01%～10% drug molecule and soak.
The preparation method who the present invention relates to the medicine carrying contact lenses is that polymerization single polymerization monomer, crosslinking chemical, single substituted cyclodextrin monomer and initiating agent and mixing diluents is even, inject mould, cause curing with ultraviolet light or heating, immerse in the solvent after the demoulding, remove unreacted monomer, obtain the cross-linked polymer hydrogel contact lens, be placed on concentration then and be in the aqueous solution of 0.01%～10% medicine and soak, described medicine is one or more in acetazolamide, methazolamide, Puerarin, prostaglandin, PILO, cyclosporine, dexamethasone, the Dipivefrine.Described thinning agent is one or more in water, isopropyl alcohol, the n-propanol.
The medicine that loads is an ophthalmic administration, as acetazolamide, and methazolamide, Puerarins etc. comprise above-mentioned medicine but are not subject to described medicine, and feature is an ophthalmic remedy, and this ophthalmic remedy can form inclusion compound with cyclodextrin molecular.
Above mentioned cyclodextrin is an alpha-cyclodextrin, beta-schardinger dextrin-, one or more in the gamma-cyclodextrin.Cyclodextrin Determination on content in the contact lenses:
According to document (Koh, G.L., Tucker, I.G., 1986.Variability in thephenol-sulphuric acid assay for sodium carboxymethylcellulose.Int.J.Pharm.34, method 183-184.) is measured cyclodextrin content.
Take by weighing the dry contact lenses that contain cyclodextrin (approximately 25mg), be immersed in 15ml, 0.5molL
-1In the concentrated sulphuric acid, reaction is 8 hours under 100 ℃ of temperature, so that the cyclodextrin complete hydrolysis in the polymeric material. hydrolyzate shifts constant volume fully in the 50ml volumetric flask, get said hydrolyzed liquid 1.25ml and add 0.75ml, 5% (m/m) phenol solution and the 4.5ml concentrated sulphuric acid, chromogenic reaction is carried out in vibration, and 490nm measures absorbance.
Transmittance is measured:
Compare with pure HEMA gel mould, do not have the vision difference to think that promptly light transmission is good. moisture measurement:
Carrying out according to weight method. the film of preparation soaked 6 hours in 70 ℃ of water, extracted unreacted monomer. and get the membrane material of swelling equilibrium, with the water of filter paper absorption surface adsorption, put into 105 ℃ of baking ovens 24 hours, taking-up is weighed.
Water cut (%)=(W
w-W
d)/Ww
W
wFilm weight for swelling equilibrium; W
dWeight for dry film.
Mechanical strength is measured:
Instron mechanics analyzer, condition determination: 14 ℃ of temperature, humidity 60%, the preparation of the single substituted ethylene basic ring of rate of extension 20mm/min. dextrin monomer GMA-EDA-CD:
According to document (Synthesis and Characterization of β-Cyclodextrin BasedFunctional Monomers and its Copolymers with N-isopropylacrylamide.Macromol.Biosci.2003,3, the structural formula that synthetic method 715-719.) prepares .GMA-EDA-CD is:
Method according to document (A.L.Lewis, A.C.Marie, et al.[P] .US0152786A1,2003,08,14) is synthetic.
Below by specific embodiment this patent is described, but the present invention and being not limited by the following examples.
Embodiment 1
Take by weighing 1g monomer HEMA, the ratio of according to the form below 1 adds above-mentioned single substituted ethylene basic ring dextrin monomer GMA-EDA-CD, the Ethylene glycol dimethacrylate (EGDMA) that adds 0.3% (total monomer weight) is a crosslinking chemical, 0.4% Darocur 1173 is as initiating agent, stir, after the vacuum outgas, be added in the polypropylene contact lens molds, at wavelength is 365nm, intensity 30mW/cm
2Ultraviolet light solidified 30 minutes down, open mould, put into the warm water demoulding, extract unreacted monomer then, obtain hydrogel contact lens.
Hydrogel contact lens to preparation characterizes, and the hydrogel contact lens light transmission that contains cyclodextrin is good, water cut 40%～60%, and relevant mechanical property sees the following form:
Cyclodextrin content and mechanical property in table 1 contact lenses
Take by weighing the HEMA of 0.5g, 0.5gNVP, the methyl acrylate that adds 0.0824g, the above-mentioned single substituted ethylene basic ring dextrin monomer GMA-EDA-CD of 0.33g, the Ethylene glycol dimethacrylate of adding 0.0039g, the Darocur 1173 of 0.4wt.% is as initiating agent, stir, after the vacuum outgas, be added in the polypropylene contact lens molds, wavelength 365nm, intensity 30mW/cm
2Ultraviolet light solidified 30 minutes down, open mould, put into the warm water demoulding, extract unreacted monomer, obtain hydrogel contact lens. the hydrogel contact lens light transmission that contains cyclodextrin is good, water cut 65%.
Take by weighing the HEMA of 0.5g, 0.5gNVP, the ethyl acrylate that adds 0.0821g, the above-mentioned single substituted ethylene basic ring dextrin monomer GMA-EDA-CD of 0.33g, the Ethylene glycol dimethacrylate of adding 0.0038g, the Darocur 1173 of 0.4wt.% is as initiating agent, stir, after the vacuum outgas, be added drop-wise in the polypropylene contact lens molds, wavelength 365nm, intensity 30mW/cm
2Ultraviolet light solidified 30 minutes down, open mould, put into the warm water demoulding, obtain hydrogel contact lens, light transmission is good, water cut 64%.
Embodiment 4
Take by weighing 1gHEMA, the single substituted ethylene basic ring dextrin monomer GMA-EDA-CD that adds 0.0221g methacrylic acid and 0.33g, the Ethylene glycol dimethacrylate that adds 0.0038g is made crosslinking chemical, the Darocur 1173 of 0.4wt.% is as initiating agent, stir, after the vacuum outgas, be added in the polypropylene contact lens molds, wavelength 365nm, intensity 30mW/cm
2Ultraviolet light solidified 30 minutes down, open mould, put into the warm water demoulding, obtain hydrogel contact lens, light transmission is good, water cut 67%.
Take by weighing HEMA and the 0.5gVMA of 0.5g, 0.33g above-mentioned single substituted ethylene basic ring dextrin monomer GMA-EDA-CD, 0.0038g Ethylene glycol dimethacrylate, 1.33g water make solvent, the Darocur 1173 of 0.4wt.% stirs as initiating agent, after the vacuum outgas, be added drop-wise in the polypropylene contact lens molds wavelength 365nm, intensity 30mW/cm
2Ultraviolet light solidified 30 minutes down, open mould, put into the warm water demoulding, characterize, product hydrogel contact lens light transmission is good, water cut 71%.
Take by weighing TRIS and the 0.5gDMA of 0.5g, 0.33g above-mentioned single substituted ethylene basic ring dextrin monomer GMA-EDA-CD, 0.0037g Ethylene glycol dimethacrylate, the Darocur 1173 of 0.4wt.% stirs as initiating agent, after the vacuum outgas, be added in the polypropylene contact lens molds wavelength 365nm, intensity 30mW/cm
2Ultraviolet light solidified 30 minutes down, open mould, put into the warm water demoulding, obtain hydrogel contact lens, water cut 41%, good mechanical properties.
Embodiment 7
Take by weighing the TRIS of 0.35g, 0.35g MA-PDMS-MA and the DMA of 0.3g, 0.33g above-mentioned single substituted ethylene basic ring dextrin monomer, the Ethylene glycol dimethacrylate of 0.0037g, the ethanol of 1.33g is made solvent, the Darocur 1173 of 0.4wt.% is as initiating agent, stir, after the vacuum outgas, be added in the polypropylene contact lens molds, wavelength 365nm, intensity 30mW/cm
2Ultraviolet light solidified 60 minutes down, open mould, put into the warm water demoulding, obtain hydrogel contact lens, water cut 38%, good mechanical properties.
Drug loading and release in vitro
Adopting the contact lenses of embodiment 1 preparation, is model drug with the Puerarin, carries out drug loading and release in vitro.
Configuration 0.16mgml
-1Puerarin solution, the contact lenses that contain the different rings dextrin content of embodiment 1 preparation are immersed in the soup, measured the absorbance (250nm) of soup every 2 hours, monitor the medicine load condition of contact lens material, after absorbance is stable, the medicine extracorporeal releasing test is carried out in taking-up. and extracorporeal releasing test carries out in 37 ℃ of incubators, and hunting speed is that the cumulative release amount after the 100r/min. drug loading discharges fully according to medicine is calculated. the drug loading of each contact lenses and release profiles See Figure 1. (weight of each contact lenses is pressed 40mg and calculated).
Embodiment 9
Adopting the contact lens sample 3 of embodiment 1 preparation, is model drug with the Puerarin, carries out the intraocular drug release experiment.
The contact lens sample 3 (cyclodextrin content 30.34%) of embodiment 1 preparation was soaked 24 hours in Puerarin soup (concentration is 0.334mg/ml or 0.802mg/ml), carry out medicine carrying, blot the soup on surface with filter paper, wear in the rabbit left eye (5), 1% listing Puerarin eye drops 50 μ l splash into right eye in contrast 1, the contact lenses reference substance of embodiment 1 preparation contrasts 2 according to contact lens sample 3 same routine processes as the contact lenses that do not contain cyclodextrin, get tear at the time point of setting with the quantitative kapillary of 1 μ l, transfer to 10 μ l, 0.5M perchloric acid solution in, add 40 μ l ultrapure waters again, content of puerarin in the high effective liquid chromatography for measuring tear the results are shown in Figure 3.
The contact lenses (cyclodextrin content 30.34%) of embodiment 1 preparation soak medicine carrying in Puerarin soup (concentration 0.802mg/ml), blot the soup on surface with filter paper, wear in the rabbit left eye (4/sampling spot), 1% listing Puerarin eye drops 50 μ l splash into right eye in contrast, at the time point of setting, get aqueous humor 0.1ml with the 1ml disposable syringe, centrifugal, get content of puerarin in the supernatant high effective liquid chromatography for measuring aqueous humor, the results are shown in Figure 4.
Claims (8)
1. medicine carrying contact lenses is characterized in that a kind of mixing in cross-linked polymer hydrogel that these medicine carrying contact lenses comprise that single substituted cyclodextrin monomer, polymerization single polymerization monomer, crosslinking chemical copolymerization obtain and acetazolamide, methazolamide, Puerarin or the prostaglandin.
2. a kind of medicine carrying contact lenses according to claim 1 is characterized in that described single substituted cyclodextrin monomer is:
Wherein:
Be alpha-cyclodextrin or beta-schardinger dextrin-or gamma-cyclodextrin; A is N or O heteroatoms, R
1For alkyl or contain N, the hydrocarbon of O atom, R
2Be methyl or H.
3. a kind of medicine carrying contact lenses according to claim 1, it is characterized in that described polymerization single polymerization monomer is: 2-hydroxyethyl methacry-late, the N-vinyl pyrrolidone, (methyl) methyl acrylate or (methyl) ethyl acrylate, (methyl) acrylic acid, N-vinylamide, DMAA, 3-methacryloxypropyl three (trimethylsiloxy) silane, the big monomer of organosilicon, the potpourri of wherein one or more.
4. a kind of medicine carrying contact lenses according to claim 1 is characterized in that described crosslinking chemical is: two or three (methyl) acrylic acid multielement alcohol ester.
5. medicine carrying contact lenses according to claim 3 is characterized in that the big monomer of organosilicon is:
R wherein
1Be methyl or hydrogen; R
2, R
3, R
4, R
5Be C
1~ C
12Alkyl or trimethylsiloxane group group; X is-NHCOO-or-OOCNH-R-NHCOO-, wherein R is C
4~ C
13Alkyl; A, c are that 1 ~ 20 integer, d are that 2 ~ 30 integer, b are 0 ~ 20 integer; Y is the combination of following structure 1 and structure 2,
Wherein structural units is 0.1 ~ 10 than e/f; R
6, R
7Be C
1~ C
12Hydrocarbon group or fluorine-containing C
1~ C
12Hydrocarbon group, R
8, R
9For hydrocarbon group or contain the hydrocarbon group of oxygen atom.
6. the preparation method of medicine carrying contact lenses as claimed in claim 1, it is characterized in that: with polymerization single polymerization monomer, crosslinking chemical, single substituted cyclodextrin monomer and initiating agent mix, inject mould, cause curing with ultraviolet light or heating, immerse in the solvent after the demoulding, remove unreacted monomer, obtain the cross-linked polymer hydrogel contact lens, be placed on concentration then and be in the aqueous solution of 0.01% ~ 10% medicine and soak, described medicine is an acetazolamide, methazolamide, Puerarin, prostaglandin, PILO, cyclosporine, dexamethasone, in the Dipivefrine one or more.
7. the preparation method of medicine carrying contact lenses according to claim 6 is characterized in that described solvent is one or more in water, saline solution, isopropyl alcohol, ethanol, the phosphate buffer.
8. the preparation method of medicine carrying contact lenses according to claim 6, it is characterized in that: add thinning agent when polymerization single polymerization monomer, crosslinking chemical, single substituted cyclodextrin monomer and initiating agent are mixed, described thinning agent is one or more in water, isopropyl alcohol, the n-propanol.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| TW201302244A (en) | 2011-07-08 | 2013-01-16 | Univ Nat Chiao Tung | Drug-carrying contact lens and manufacturing method thereof |
| US9827250B2 (en) | 2012-07-31 | 2017-11-28 | Johnson & Johnson Vision Care, Inc. | Lens incorporating myopia control optics and muscarinic agents |
| US8820924B2 (en) * | 2012-07-31 | 2014-09-02 | Johnson & Johnson Vision Care, Inc. | Inversion marking for contact lenses |
| KR101371685B1 (en) * | 2012-10-30 | 2014-03-10 | 김선호 | Therapeutic contact lens |
| CN104877068B (en) * | 2015-05-21 | 2017-08-25 | 爱生华(苏州)光学有限公司 | A kind of preparation method of practical silicone hydrogel contact mirror |
| US10564076B2 (en) | 2015-06-16 | 2020-02-18 | Agilent Technologies, Inc. | Compositions and methods for analytical sample preparation |
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| TW202009013A (en) * | 2018-08-14 | 2020-03-01 | 優你康光學股份有限公司 | Contact lenses with functional components and products thereof |
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| CN114545658B (en) * | 2022-02-25 | 2023-07-14 | 金陵科技学院 | Preparation method of drug-sustained-release interpenetrating network hydrogel contact lens |
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