CN113136012A

CN113136012A - Medical device and manufacturing method thereof

Info

Publication number: CN113136012A
Application number: CN202010067072.3A
Authority: CN
Inventors: 闫文霞; 隋信策; 禹杰; 解江冰
Original assignee: Abbott Beijing Medical Technology Co ltd
Current assignee: Abbott Beijing Medical Technology Co ltd; Eyebright Medical Technology Beijing Co Ltd
Priority date: 2020-01-20
Filing date: 2020-01-20
Publication date: 2021-07-20
Also published as: WO2021147919A1

Abstract

The present invention relates to a medical device and a method of manufacturing the same. Further, the present invention relates to a medical device such as a contact lens having durable moisture retention. More particularly, the present invention relates to a medical device having a long-lasting moisture retention property manufactured by immobilizing a hydrophilic polymer on a substrate.

Description

Medical device and manufacturing method thereof

Technical Field

Background

As consumers' interest in eye health increases, more and more people are pursuing comfort and health of contact lens wear. The silicon hydrogel contact lenses are on the market, so that the defects of the traditional hydrogel material lenses in the aspects of oxygen permeability, comfort, health, cleanness and the like are overcome one by one.

The silicone hydrogel, also called silicone hydrogel polymer, is an organic high molecular material, has hydrophilicity and a two-phase material framework, namely has two channels of silicone and hydrogel. Simply speaking, the silicone molecules and the hydrogel material are polymerized together. The organic silicon monomer has loose structure, small intermolecular force and large free space volume, and is always used as an oxygen-enriched film polymer material with the highest oxygen permeation coefficient to be widely applied to medical instruments such as contact lenses and the like. The water in the silicone hydrogel contact lens provides the desired softness, and a higher water content is beneficial for its biocompatibility and comfort. However, a water content that is too high (above 80%) can affect not only the mechanical strength and rigidity, but also the oxygen permeability of the material.

The structure and material composition of the contact lens surface can significantly affect the surface properties of the contact lens, such as wettability, friction, adhesion, or lubricity. Silicones are hydrophobic and surface modification methods are generally needed to reduce or eliminate silicone exposure on the surface of silicone hydrogel contact lenses, maintain their hydrophilic surface, and improve comfort during wear. The prior art includes the preparation of hydrophilic polysiloxanes and the modification of the lens surface. Hydrophilic polysiloxanes are prepared by grafting hydrophilic segments onto the backbone or side chains of siloxane macromolecules to increase their hydrophilicity (e.g. the Baimine contact lenses manufactured by Kubo,

) (ii) a Lens surface modification includes plasma treatment (e.g., Eler)Contact lenses of the day and night type, CIBA, manufactured by KANG corporation

Clear vision contact lenses manufactured by bos & lun corporation,

) And physically and/or chemically embedding an internal wetting agent (e.g., Enchand oxygen contact lens, ACUVUE, manufactured by Johnson corporation) in the silicone hydrogel polymer matrix

)。

Researchers have alleviated this problem by coating the surface of a silicone hydrogel contact lens with a hydrophilic coating, such as a plasma coating. For example, there is a patent (CN1189506C) that discloses improving the compatibility of lenses with ocular surfaces by applying a plasma coating to the surface of a contact lens or treating the surface of a contact lens with a reactive hydrophilic polymer. The hydrophilic surface is created by chemically linking reactive functional groups of the contact lens substrate with reactive functional groups of the hydrophilic polymer. The reaction conditions generally required by the technology are harsh, a catalyst needs to be added, the reaction is carried out in a high-pressure environment, the operation process is complicated, and the requirement is high; in addition, the selection range of the technology for the contact lens substrate is narrow, and the lens needs to contain a large number of active functional groups such as amino, carboxyl, epoxy and the like, so that the application range of the technology is limited. Secondly, besides the narrow application range of the lens, the active hydrophilic polymer needs additional steps such as synthesis, preparation, separation and purification, etc., so that the production period of the contact lens is prolonged, and the cost is increased. For example, the vinyl pyrrolidone- (4-vinyl cyclohexyl-1, 2-epoxide) copolymer needs to be prepared, and the hydrophilic polymer is fixed on the surface of the lens by utilizing the reaction of the epoxy group of the hydrophilic polymer and the carboxyl group in the contact lens substrate, and the synthesis, preparation, separation and purification processes of the vinyl pyrrolidone- (4-vinyl cyclohexyl-1, 2-epoxide) copolymer need to be added in the technology, so that the cost is increased, and pollution and waste are caused.

Another more established technique is to incorporate hydrophilic wetting agents into the monomer composition from which the contact lens is made. The difficulty with this technique is the problem of incompatibility of the silicone macromolecules with the hydrophilic polymer, and the problem of the incorporation of hydrophilic wetting agents which, due to their non-covalent bonding with the lens matrix material, may leach out of the lens over time resulting in a reduction in effectiveness. There is a known technique for adding poly (N-vinyl-2-pyrrolidone) (PVP) to silicone hydrogel compositions to form interpenetrating networks having a low degree of surface friction, a low dehydration rate, and a high degree of resistance to biological deposits. PVP of high molecular weight (Mw greater than 300,000) can be embedded within the crosslinked silicone hydrogel matrix. However, a small loss of high molecular weight PVP (less than 10%) was still observed during the organic solvent extraction purification. Thus, there is a published patent (CN100578263C) that incorporates an active hydrophilic wetting agent into a monomer composition for making contact lenses, significantly improving the wettability of the contact lens surface. The end group of the active hydrophilic wetting agent contains unsaturated double bonds, and the active hydrophilic wetting agent is polymerized and fixed in the lens making process, so that the loss in the subsequent extraction and purification process is low. However, the active hydrophilic wetting agent also has the problems of synthetic preparation, separation and purification.

Chinese patent CN104774288B discloses a manufacturing technique of super-hydrophilic silicone hydrogel lens, which adds free hydrophilic polymers during the silicone hydrogel lens forming process, and the free hydrophilic polymers inside the lens react with the hydrophilic polymers added in addition during the post-treatment process (heating and then gradually cooling) to form a large amount of hydrophilic networks, so as to obtain super-hydrophilicity.

The present inventors have desired to find a simple, efficient, and inexpensive post-treatment technique for moisturizing silicone hydrogel lenses, which not only "locks" the hydrophilic polymer (moisturizing agent) in the interior and/or on the surface of the lens, but also covalently bonds the hydrophilic polymer to the substrate material, thereby achieving a long-lasting improvement in the comfort of the lens.

Disclosure of Invention

Problems to be solved by the invention

The invention aims to solve the problems that the moisture retention of the medical device in the prior art, particularly the contact lens is difficult to last, the hydrophilic polymer and the substrate can not be firmly combined, and the hydrophilicity and the lubricating effect of the surface are poor in a wearing state, and develops a medical device which has the advantages that the moisture retention is lasting, the hydrophilic polymer and the substrate are firmly combined, and the hydrophilicity and the lubricating effect of the surface are kept for at least more than half a year in the wearing state.

Means for solving the problems

The invention fixes the hydrophilic polymer or the hydrophilic polymer prepared by the hydrophilic monomer on the contact lens substrate in a chemical crosslinking way, so as to manufacture medical devices with lasting moisture retention, lubrication and hydrophilic characteristics, in particular contact lenses, and reduce or even eliminate the wearing discomfort phenomena of lens hydrophobicity, adhesion, acerbity and the like caused by the migration and exposure of siloxane on the surface of the lens.

Specifically, the present invention proposes the following technical solutions.

[1] The present invention provides a medical device having a substrate, and a hydrophilic polymer immobilized on the substrate by chemical crosslinking, wherein the chemical crosslinking occurs between alkyl chain radical active sites of the hydrophilic polymer and/or between alkyl chain radical active sites of the hydrophilic polymer and radical active sites of the substrate; these free radical reactive sites are generated by the reaction of an oxidizing agent with the hydrophilic polymer and/or substrate material.

[2] The medical device according to the above [1], wherein the hydrophilic polymer fixed on the substrate accounts for 0.1 to 20 mass%, preferably 5 to 15 mass% of the total dry mass of the substrate.

[3] The medical device according to the above [1], wherein the hydrophilic polymer is one or more selected from the group consisting of hydrophilic polymers having a cyclic amide or cyclic imine structure in the main chain, poly-N, N-dimethylacrylamide, polyvinyl alcohol, polyethylene glycol, polyacrylic acid, polyethylene oxide, poly-2-ethyl-oxazoline, polymers containing a phosphorylcholine vinyl monomer, and polysaccharides, and is preferably polyvinylpyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-piperidone, poly-N-vinyl-2-piperidone, poly-vinyl-N-methyl-2-piperidone, poly-amide, poly-N-vinyl-2-methyl-oxazoline, poly-amide, poly-N-vinyl-2-methyl-amide, poly-N-amide, poly-2-amide, poly-amide, and poly-amide, and poly-amide, poly-amide, poly-amide, poly-2-amide, poly-amide, and poly, One or more of poly N-vinyl-4-methyl-2-caprolactam, poly N-vinyl-3-ethyl-2-pyrrolidone, poly N-vinyl-4, 5-dimethyl-2-pyrrolidone and polyvinyl imidazole.

[4] The medical device according to [1] above, wherein the weight average molecular weight of the hydrophilic polymer is 50000 or more, preferably 50000 to 1500000, and more preferably 200000 to 1500000.

[5] The medical device according to the above [1], wherein the oxidizing agent is one or more selected from the group consisting of peroxides and persulfides, preferably one or more selected from the group consisting of hydrogen peroxide, potassium persulfate, sodium persulfate and ammonium persulfate.

[6] The medical device according to any one of the above [1] to [5], wherein it satisfies at least one of the following characteristics:

(1) the medical device has a sustained release rate of less than 5%, preferably less than 1%, more preferably less than 0.1% after being soaked in a standard salt solution for 1 year;

(2) the water content of the medical device is 20-60%, preferably 30-50%, more preferably 35-45%;

(3) compared with the substrate, the water content of the medical device is improved by 0.5-5%, preferably 1-2%;

(4) the medical device has a coefficient of friction of less than 0.2, preferably less than 0.05;

(5) the static water contact angle of the surface of the medical device is less than 90 °, preferably less than 60 °, more preferably less than 40 °.

[7] The medical device according to any one of the above [1] to [6], wherein the medical device is a contact lens, and the substrate is a contact lens substrate, preferably a silicone hydrogel contact lens substrate.

[8] The medical device according to any one of the above [1] to [7], wherein the material of the substrate is copolymerized from at least a silicon-containing monomer and/or a prepolymer of a silicon-containing monomer and a hydrophilic monomer, and the mass ratio of the silicon-containing monomer and/or the prepolymer of a silicon-containing monomer to the hydrophilic monomer, that is, the mass ratio of the silicon-containing monomer and/or the prepolymer of a silicon-containing monomer: the mass ratio of the hydrophilic monomer is (40-70) to (30-60); preferably, the substrate material further comprises a diluent; more preferably, the diluent is a solvent and/or a hydrophilic polymer.

[9] The medical device according to the above [8], wherein the silicon-containing monomer and/or the prepolymer of the silicon-containing monomer is selected from one or more of a mono-or di-terminated acryloxy or methacryloxy and acrylamido or methacrylamido terminated silicone monomer, and/or acryloxy or methacryloxy and acrylamido or methacrylamido mono-or di-terminated polysiloxane;

preferably, the silicon-containing monomer is selected from the group consisting of 3- [ tris (trimethylsiloxy) silyl ] propyl methacrylate, 3- (trimethylsiloxy) propyl acrylate, 3- [ diethoxy (meth) silyl ] propyl methacrylate, 3- (trimethoxysilyl) propyl methacrylate, 3- [ dimethoxy (meth) silyl ] propyl methacrylate, 3- (methoxydimethylsilyl) propyl acrylate, 3- (triethoxysilyl) propyl methacrylate, allyltris (trimethylsiloxy) silane, allyltrimethoxysilane, 1,1,1,5,5, 5-hexamethyl-3- [ (trimethylsiloxy) oxy ] -3-vinyltrisiloxane, allyltriethoxysilane, vinyltrimethoxysilane, a mixture thereof, and a mixture thereof, One or more of triethoxyvinylsilane, vinyltris (2-methoxyethoxy) silane, 2- (trimethylsiloxy) ethyl methacrylate, tetrakis [ dimethyl (vinyl) siloxy ] silane, acrylamidopropyltrimethoxysilane, (3-methacrylamidopropyl) triethoxysilane, 3-acrylamidopropyltris (trimethylsiloxy) silane, (3-methacrylamidopropyl) tris (trimethylsiloxy) silane;

preferably, the prepolymer of the silicon-containing monomer is selected from one or more of acryloxy or methacryloxy and acrylamide or methacrylamide mono-terminated or di-terminated polydimethylsiloxane, and the weight average molecular weight of the prepolymer of the silicon-containing monomer is more than 1000, preferably 1500 to 50000, more preferably 2000 to 20000;

the hydrophilic monomer is selected from one or more of acrylate monomer, acrylamide monomer and vinyl monomer;

preferably, the hydrophilic monomer is selected from the group consisting of hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxypropyl acrylate, vinylpyrrolidone, ethoxyethyl methacrylate, ethoxyethyl acrylate, methoxyethyl methacrylate, methoxyethyl acrylate, ethylene glycol (meth) acrylate, glycidyl methacrylate, glycerol monomethacrylate, glycidyl acrylate, acrylic acid, methacrylic acid, 2- (trifluoromethyl) acrylic acid, dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate, N-dimethylmethacrylamide, N-dimethylacrylamide, N-diethylaminoethyl acrylate, N-diethylaminoethyl methacrylate, N-tert-butylacrylamide, N-butylacrylamide, and mixtures thereof, One or more of N-tert-butyl methacrylamide, N-isopropyl acrylamide, N-isopropyl methacrylamide, phenylacrylic acid, acrylamide, methacrylamide, N-methylol acrylamide and N-methylol methacrylamide.

[10] The present invention also provides a method of manufacturing the medical device according to any one of the above [1] to [9], including: manufacturing a substrate, immersing the substrate in a solution containing the hydrophilic polymer and/or the hydrophilic monomer and an oxidizing agent, followed by a chemical reaction, thereby manufacturing the medical device.

[11] The method according to the above [10], wherein the chemical reaction is a chemical crosslinking reaction, and the temperature of the chemical reaction is 20 to 200 ℃, preferably 50 to 150 ℃, and more preferably 70 to 120 ℃.

[12] The method according to any one of the above [10] to [11], wherein the immersing of the substrate in the solution containing the hydrophilic polymer and/or the hydrophilic monomer and the oxidizing agent comprises: simultaneously adding the hydrophilic polymer and/or the hydrophilic monomer and the oxidant into a solvent to form a mixed solution, and then soaking the substrate in the mixed solution; or, respectively dissolving the hydrophilic polymer and/or the hydrophilic monomer and the oxidant in a solvent, and then soaking the substrate in the hydrophilic polymer solution and/or the hydrophilic monomer solution and the oxidant solution respectively;

preferably, the substrate is soaked in the oxidant solution and then soaked in the hydrophilic polymer solution and/or the hydrophilic monomer solution;

preferably, the mass concentration of the hydrophilic polymer solution is 0.1-20%, preferably 0.3-15%, and more preferably 0.5-10%;

preferably, the mass concentration of the hydrophilic monomer solution is 0.1-20%, preferably 1-15%, more preferably 3-10%;

preferably, the mass concentration of the oxidant solution is 0.01% to 10%, preferably 0.05% to 7%, and more preferably 0.1% to 5%.

ADVANTAGEOUS EFFECTS OF INVENTION

In the medical device of the present invention, the hydrophilic polymer attracts water molecules by hydrogen bonds in an aqueous environment, not only increasing the hydrophilicity of the surface of the medical device (e.g., contact lens), but also suitably increasing the water content of the medical device, for example, by about 2%. In addition, the hydrophilic polymer immobilized by chemical crosslinking can control the coating density of the hydrophilic polymer on the lens surface of a medical device, such as a contact lens, by controlling the crosslinking density, reduce the friction coefficient (<0.2, preferably <0.05) of the lens surface of a medical device, such as a contact lens, and improve lubricity.

Since the hydrophilic polymer is fixed by chemical crosslinking, it has substantially no dissolution loss and a very low sustained release rate (α < 5%, preferably α < 1%, more preferably α < 0.1%) in the medical device. Therefore, the medical device of the invention has lasting moisture retention, the hydrophilic polymer is firmly combined with the substrate, and the hydrophilic and lubricating effects on the surface of the medical device are maintained for at least more than half a year in a wearing state.

Drawings

FIG. 1 is a thermodynamic diagram (glass transition temperature T) of a substrate prepared in example 2_g/℃)。

FIG. 2 is a thermodynamic diagram (melting point temperature T) of a substrate prepared in example 2_m/℃)。

FIG. 3 is a thermodynamic diagram (glass transition temperature T) of a medical device prepared in example 8_g/℃)。

FIG. 4 is a thermodynamic diagram (melting point temperature T) of a medical device prepared in example 8_m/℃)。

Detailed Description

< medical device >

The present invention provides a medical device having a substrate, and a hydrophilic polymer immobilized on the substrate by chemical crosslinking, wherein the chemical crosslinking occurs between alkyl chain radical active sites of the hydrophilic polymer and/or between alkyl chain radical active sites of the hydrophilic polymer and radical active sites of the substrate; these free radical reactive sites are generated by the reaction of an oxidizing agent with the hydrophilic polymer and/or substrate material.

The substrate is made of at least a silicon-containing monomer and/or a prepolymer of the silicon-containing monomer and a hydrophilic monomer through copolymerization, and the hydrophilic polymer fixed on the substrate accounts for 0.1-20% of the total dry mass of the substrate, preferably 5-15%.

In the present invention, the immobilization of the hydrophilic polymer on the substrate may be achieved by: the hydrophilic polymer is singly swelled into the substrate and then fixed by chemical crosslinking, or the hydrophilic monomer is swelled into the substrate, and in-situ polymerized on the substrate framework to generate the polymer, and then the polymer is alternately interpenetrated with the substrate framework and fixed by chemical crosslinking, or the combination of the two.

In the invention, chemical crosslinking is generated between alkyl chain free radical active points of the hydrophilic polymer and/or between alkyl chain free radical active points of the hydrophilic polymer and free radical active points of the substrate, so that more crosslinking points can be formed, the bonding firmness of the hydrophilic polymer and the substrate is increased, and the slow release speed of the hydrophilic polymer is reduced. These free radical reactive sites may be generated by reacting an oxidizing agent with the hydrophilic polymer and/or substrate material.

In the present invention, the medical device satisfies at least one of the following characteristics:

The release rate of the hydrophilic polymer, the water content of the medical device, the water content of the substrate, the friction coefficient of the medical device, and the static water contact angle of the surface of the medical device can be measured according to the respective measurement methods described in the examples.

< hydrophilic Polymer and hydrophilic monomer for polymerization to form hydrophilic Polymer >

In the present invention, the hydrophilic polymer is preferably a hydrophilic polymer having a cyclic amide or cyclic imine structure in the main chain.

The hydrophilic polymer may be selected from the group consisting of polyvinylpyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone, poly-N-vinyl-4, 5-dimethyl-2-pyrrolidone, polyvinylimidazole, poly-N, N-dimethylacrylamide, poly-N-vinyl-2-piperidone, poly-N-vinyl-4-methyl-2-piperidone, poly-N-vinyl-3-ethyl-2-pyrrolidone, poly-vinylimidazole, poly-N, N-dimethylacrylamide, poly-N-2-pyrrolidone, poly-vinyl-pyrrolidone, poly (N-methyl-2-pyrrolidone), poly (N-vinyl-methyl-2-pyrrolidone), poly (N-vinyl-methyl-2-pyrrolidone), poly (N-methyl pyrrolidone), poly (N-vinyl-2-methyl pyrrolidone), poly (N-vinyl-2-methyl pyrrolidone), poly (N-vinyl-2-vinyl-2-methyl pyrrolidone), poly (N-vinyl-pyrrolidone), poly (N-vinyl-2-vinyl-2-vinyl-2-pyrrolidone), poly (N-vinyl-2-vinyl-pyrrolidone), poly (N-vinyl-2-vinyl pyrrolidone), poly (vinyl-vinyl pyrrolidone), poly (vinyl-vinyl pyrrolidone) and poly (vinyl pyrrolidone) and, One or more (including block, random, graft, comb or star polymers) of polyvinyl alcohol, polyethylene glycol, polyacrylic acid, polyethylene oxide, poly-2-ethyl-oxazoline, polymer containing choline phosphate vinyl monomer and polysaccharide (preferably heparin polysaccharide), preferably one or more hydrophilic polymers containing cyclic amide or cyclic imine structure in the main chain, such as polyvinylpyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, and the like. The above polymers may also be used in the form of copolymers.

In the present invention, hydrophilic monomers may also be used to form hydrophilic polymers by in situ polymerization on a substrate backbone. The hydrophilic monomer used in the in situ polymerization to form the hydrophilic polymer may be selected from the group consisting of vinyl pyrrolidone, N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4, 5-dimethyl-2-pyrrolidone, vinylimidazole, N-dimethylacrylamide, N-vinyl-2-pyrrolidone, N-methyl-2-pyrrolidone, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4, 5-dimethyl-2-pyrrolidone, and mixtures thereof, One or more of vinyl alcohol, ethylene glycol, acrylic acid, ethylene oxide, 2-ethyl-oxazoline and choline-containing vinyl monomers are preferably one or more of hydrophilic monomers containing cyclic amide or cyclic imine structures, such as vinyl pyrrolidone, N-vinyl-2-piperidone and N-vinyl-2-caprolactam.

In the present invention, the hydrophilic polymer fixed on the substrate accounts for 0.1 to 20 mass%, preferably 5 to 15 mass%, of the total dry mass of the substrate. When the mass percentage is less than 0.1%, hydrophilicity, lubricity, and durability of the medical device may be affected, and when the mass percentage is more than 20%, appearance and dimensional stability of the medical device may be affected.

The weight average molecular weight of the hydrophilic polymer is 50000 or more, preferably 50000-1500000, and more preferably 200000-1500000.

< substrate >

In the invention, the material of the substrate is at least copolymerized by a silicon-containing monomer and/or a prepolymer of the silicon-containing monomer and a hydrophilic monomer.

The silicon-containing monomer is selected from one or more of single-end-capped or double-end-capped acryloyloxy or methacryloyloxy and acrylamide-end-capped or methacrylamide-end-capped small molecule organic silicon monomers; preferably 3- [ tris (trimethylsiloxy) silyl ] propyl methacrylate, 3- (trimethylsiloxy) propyl acrylate, 3- [ diethoxy (meth) silyl ] propyl methacrylate, 3- (trimethoxysilyl) propyl methacrylate, 3- [ dimethoxy (meth) silyl ] propyl methacrylate, 3- (methoxydimethylsilyl) propyl acrylate, 3- (triethoxysilyl) propyl methacrylate, allyltris (trimethylsiloxy) silane, allyltrimethoxysilane, 1,1,1,5,5, 5-hexamethyl-3- [ (trimethylsilyl) oxy ] -3-vinyltrisiloxane, allyltriethoxysilane, vinyltrimethoxysilane, vinyltrisiloxane, One or more of triethoxyvinylsilane, vinyltris (2-methoxyethoxy) silane, 2- (trimethylsiloxy) ethyl methacrylate, tetrakis [ dimethyl (vinyl) siloxy ] silane, acrylamidopropyltrimethoxysilane, (3-methacrylamidopropyl) triethoxysilane, 3-acrylamidopropyltris (trimethylsiloxy) silane, and (3-methacrylamidopropyl) tris (trimethylsiloxy) silane.

The prepolymer of the silicon-containing monomer is selected from one or more of acryloyloxy or methacryloyloxy and acrylamide-based or methacrylamide-based mono-terminated or di-terminated long-chain polysiloxane. Preferably one or more of acryloxy or methacryloxy and acrylamido or methacrylamido mono-or di-endblocked polydimethylsiloxanes. The weight average molecular weight of the prepolymer containing the silicon monomer is more than 1000, preferably 1500-50000, and more preferably 2000-20000.

The hydrophilic monomer forming the substrate material is selected from one or more of acrylate monomer, acrylamide monomer and vinyl monomer; preferably, the hydrophilic monomer is selected from the group consisting of hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxypropyl acrylate, vinylpyrrolidone, ethoxyethyl methacrylate, ethoxyethyl acrylate, methoxyethyl methacrylate, methoxyethyl acrylate, ethylene glycol (meth) acrylate, glycidyl methacrylate, glycerol monomethacrylate, glycidyl acrylate, acrylic acid, methacrylic acid, 2- (trifluoromethyl) acrylic acid, dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate, N-dimethylmethacrylamide, N-dimethylacrylamide, N-diethylaminoethyl acrylate, N-diethylaminoethyl methacrylate, N-tert-butylacrylamide, N-butylacrylamide, and mixtures thereof, One or more of N-tert-butyl methacrylamide, N-isopropyl acrylamide, N-isopropyl methacrylamide, phenylacrylic acid, acrylamide, methacrylamide, N-methylol acrylamide and N-methylol methacrylamide.

The mass ratio of the silicon-containing monomer and/or the prepolymer of the silicon-containing monomer to the hydrophilic monomer in the substrate material is as follows, namely the mass ratio of the silicon-containing monomer and/or the prepolymer of the silicon-containing monomer: the mass ratio of the hydrophilic monomer is (40-70) to (30-60). When the ratio is out of this range, the substrate cannot be cured or the yield is extremely low, thereby affecting the production and cost of the medical device of the present invention.

In the present invention, the substrate is produced by copolymerizing at least a silicon-containing monomer and/or a silicon-containing monomer prepolymer with a hydrophilic monomer, and then molding or turning the copolymer. In the copolymerization of the silicon-containing monomer and/or the prepolymer of the silicon-containing monomer with the hydrophilic monomer, it is usually necessary to contain an initiator, and a photoinitiator or a thermal initiator may be used. The photoinitiator may be selected from, but is not limited to, benzoin methyl ether, diethoxyacetophenone, benzoylphosphine oxide type initiators, ethyl dimethylaminobenzoate, 2-isopropylthioxanthone, 1-hydroxycyclohexyl phenyl ketone, Darocure series initiators or Irgacure series initiators, and the like. The thermal initiators include, but are not limited to, azo-based or peroxy-based initiators, such as azobisisoheptonitrile, azobisisobutyronitrile, benzoyl peroxide, Trigonox series initiators, Perkdox series initiators, or the like. Irgacure-819 or Darocure-1173 is preferred.

In the present invention, the substrate material may contain a bifunctional or polyfunctional monomer for forming a crosslinked structure in the substrate material, and the monomer may be ethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, tri (ethylene glycol) dimethacrylate, tri (ethylene glycol) divinyl ether, propylene glycol dimethacrylate, glycerol dimethacrylate, 1- (acryloyloxy) -3- (methacryloyloxy) -2-propanol, or the like.

In the present invention, the substrate material may also contain ultraviolet absorbers, blue light absorbers, and dyes that enable the material to achieve different colors. Ultraviolet absorbers include, but are not limited to: selected from compounds having a highly efficient absorption function for ultraviolet rays having a wavelength range of 380nm or less. Benzophenone compounds and/or benzotriazole compounds with high safety are preferable. More preferably, the benzophenone-based compound and/or the benzotriazole-based compound contain a polymerizable group selected from a vinyl group, an allyl group, a butenyl group, an ethynyl group, an acryloyloxy group, a methacryloyloxy group, an acrylamido group, a methacrylamido group, a vinyl ether group and the like. Blue light absorbers include, but are not limited to: the blue light selective filter is selected from compounds with selective filtering function on blue light with the wavelength range of 400-500 nm. Preferably a yellow dye compound with a molecular structural formula containing azo groups. More preferred are yellow dye compounds containing a polymerizable group selected from vinyl, allyl, butenyl, ethynyl, acryloxy, methacryloxy, acrylamido, methacrylamido, vinyl ether groups, and the like. Dyes are selected from, but not limited to, compounds approved by the FDA in the united states for use in contact lenses, such as copper phthalocyanine, reactive blue 4, reactive blue 19, reactive blue 21, reactive yellow 15, reactive orange 78, reactive red 11, titanium dioxide, reactive black 5, D & C green 4, D & C blue 6, D & C green 6, D & C yellow 10, and the like.

The substrate material may also contain diluents such as solvents and/or hydrophilic polymers, etc. When the substrate material contains a diluent, the reactive components are typically mixed in the diluent to form a reaction mixture. Suitable classes of diluents for the silicone hydrogel reaction mixture include alcohols having 2 to 20 carbons, carboxylic acids having 8 to 20 carbon atoms, poly N, N-dimethylacrylamide, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, amides derived from primary amines having 10 to 20 carbon atoms and carboxylic acids having 8 to 20 carbon atoms, and the like.

Specifically, the diluent may include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3, 7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, 1-tert-butoxy-2-propanol, 3-dimethyl-2-butanol, tert-butoxyethanol, 2-octyl-1-dodecanol, di-iso-propylaminoethanol, isopropanol, 3, 7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-butanol, 2-butanol, or the like, One or more of capric acid, caprylic acid, dodecanoic acid, 2- (diisopropylamino) ethanol, poly (N, N-dimethylacrylamide), polyvinyl alcohol, polyethylene glycol and polyvinylpyrrolidone.

In the present invention, the medical device is a contact lens, particularly a long-wear contact lens, and the substrate is a contact lens substrate, preferably a silicone hydrogel contact lens substrate.

< method for producing medical device >)

The invention also provides a method of manufacturing a medical device according to the invention, comprising: manufacturing a substrate, immersing the substrate in a solution containing the hydrophilic polymer and/or the hydrophilic monomer and an oxidizing agent, followed by a chemical reaction, thereby manufacturing the medical device.

In this production method, specific types of the silicon-containing monomer or the prepolymer of the silicon-containing monomer, the hydrophilic monomer, and the hydrophilic polymer used are the same as those described above.

The oxidant is selected from one or more of peroxide or persulfate, preferably one or more of hydrogen peroxide, potassium persulfate, sodium persulfate and ammonium persulfate.

The oxidizing agent plays a key role in immobilizing the hydrophilic polymer in the interior or on the surface of the substrate.

The following equation, which is exemplified by polyvinylpyrrolidone, illustrates the mechanism by which an oxidizing agent reacts with the hydrophilic polymer and/or substrate material to generate free radicals, thereby causing the hydrophilic polymer to undergo a crosslinking reaction with the substrate material and become immobilized on a contact lens.

That is, in the prepared contact lens substrate, an oxidizing agent is dissolved in advance in the substrate, and after the hydrophilic polymer diffuses into the substrate, the alkyl chain position of the hydrophilic polymer is oxidized by the oxidizing agent to deprive a hydrogen atom, and further a radical active site is generated, and at the same time, the alkyl chain position on the substrate is also oxidized by the oxidizing agent to generate a radical active site. Free radical reaction occurs between alkyl chain free radical active points of the hydrophilic polymer and/or between the alkyl chain free radical active points of the hydrophilic polymer and the free radical active points of the substrate to generate chemical cross-linking points, so that the combination firmness is increased, and the slow release speed of the hydrophilic polymer in the medical device is reduced.

In addition, in the presence of hydrophilic monomer, the oxidizing agent may initiate polymerization, and the produced hydrophilic polymer may continue to crosslink with the substrate in the presence of excessive oxidizing agent.

The temperature of the crosslinking reaction is 20-200 ℃, preferably 50-150 ℃, and more preferably 70-120 ℃. When the temperature of the chemical reaction is outside this range, the appearance, size and properties of the prepared medical device may be affected, and the hydrophilic polymer may exist in a non-chemically crosslinked form on the substrate or may not be immobilized, thereby affecting the properties of the medical device of the present invention.

In the present invention, the immersing of the substrate in the solution containing the hydrophilic polymer and/or the hydrophilic monomer and the oxidizing agent comprises: simultaneously adding the hydrophilic polymer and/or the hydrophilic monomer and the oxidant into a solvent to form a mixed solution, and then soaking the substrate in the mixed solution; alternatively, the hydrophilic polymer and/or the hydrophilic monomer and the oxidizer are each dissolved in a solvent, and then the substrate is soaked in the hydrophilic polymer solution and/or the hydrophilic monomer solution and the oxidizer solution, respectively.

Preferably, the substrate is soaked in the oxidant solution and then soaked in the hydrophilic polymer solution and/or the hydrophilic monomer solution.

The solvent for dissolving the hydrophilic polymer and/or the hydrophilic monomer and the oxidizing agent may be the same or different, and the solvent may be selected from at least one of ethyl acetate, ethanol, propanol, isopropanol, butanol, and water.

Preferably, the mass concentration of the hydrophilic polymer solution is 0.1% to 20%, preferably 0.3% to 15%, and more preferably 0.5% to 10%.

Preferably, the mass concentration of the hydrophilic monomer solution is 0.1% to 20%, preferably 1% to 15%, and more preferably 3% to 10%.

When the mass concentration of the hydrophilic polymer solution or the hydrophilic monomer solution or the oxidant solution is not in the above range, the properties such as hydrophilicity and lubricity of the produced medical device are affected.

Examples

The present invention will be further described with reference to the following examples. It is to be understood that one skilled in the art would recognize that the present invention is not limited to the specific embodiments described.

EXAMPLES 1-5 preparation of silicon hydrogel contact lens substrates

The following Table 1 lists the types and amounts of the silicon-containing monomer or the prepolymer of the silicon-containing monomer and the hydrophilic monomer used in examples 1 to 5.

The preparation method of the substrate comprises the following steps:

the reaction components listed in Table 1 were mixed with a diluent (absolute ethanol) and stirred at room temperature for about 20 minutes until all the components were dissolvedAnd (4) decomposing to obtain a reaction preparation. Using N₂The solution was purged for about 15 minutes. Approximately 40-50 microliters of the above reaction formulation was pipetted into a clean polypropylene female mold half, followed by capping the mating polypropylene male mold half. The mold halves were pressed together and subsequently irradiated with light (PhilipsTL03, 1.6 mW/cm)²15 minutes) to carry out photopolymerization to obtain the silicone hydrogel contact lens substrates of examples 1-5.

The prepolymer containing silicon monomers used therein, i.e. Polydimethylsiloxane (PDMS), was prepared synthetically by the applicant, and the other components are commercially available. The weight average molecular weight of PDMS in Table 1 is about 4000 and the specific preparation steps are as follows:

bishydroxy-terminated silicone oil (362g, 0.2mol) and dibutyltin dilaurate (0.25g, 0.0004mol) were added to a 1000mL three-necked round bottom flask equipped with a stirring paddle and a nitrogen inlet. Isophorone diisocyanate (22.2g, 0.1mol) was weighed into a dropping funnel, the dropping speed was adjusted to complete the dropping for about 3 hours, and the reaction was continued for 1 hour with prolonged duration. Isocyanoethyl methacrylate (31g, 0.2mol) was then transferred to a dropping funnel, and the dropping speed was adjusted to complete the dropping for about 1 hour, and the reaction was continued for an extended period of 4 hours. The temperature to which the reaction mixture was heated throughout was 40 ℃. And after the reaction is finished, closing the heating device and the stirring device, and subpackaging for later use after the product is naturally cooled.

TABLE 1

Examples	PDMS	TRIS	NVP	DMA	HEMA	TMPTMA	D1173	RB19	UV416	ETOH
											1	28	17	28	5	1.43	0.05	0.5	0.02	/	20
2	43	/	40	5	5.42	0.05	1.0	0.03	0.5	5
											3	65	/	/	29	1.92	0.05	1.5	0.03	0.5	2
4	/	48	42	5	3.78	0.20	0.5	0.02	0.5	/
											5	/	41	/	45	12.78	0.20	0.5	0.02	0.5	/

Note: the amounts of the respective components in table 1 are in terms of mass percentage based on the total mass (100%) of the respective components.

PDMS: polydimethylsiloxane

TRIS: methacryloxypropyl tris (trimethylsiloxy) silane

NVP: vinyl pyrrolidone

DMA: n, N-dimethylacrylamide

HEMA: hydroxy ethyl methacrylate

TMPTMA: trimethylolpropane trimethacrylate

D1173: 2-hydroxy-2-methyl-1-phenyl-1-propanone

RB 19: reactive blue 19

UV 416: 2- (4-benzoyl-3-hydroxyphenoxy) ethyl 2-acrylate

ETOH: anhydrous ethanol

Examples 6-12 preparation of contact lenses with Long-lasting moisture Retention

In these examples, experiments were conducted with the contact lens substrates prepared in examples 1-5. At room temperature, the contact lens substrates prepared in examples 1 to 5 were respectively placed in a standard phosphate buffer solution for overnight equilibration, then transferred to a vacuum drying oven at 60 ℃ for drying to constant weight, and the samples were taken out and placed in a dryer for cooling.

The hydrophilic monomer is vinyl pyrrolidone (NVP), the hydrophilic polymer is polyvinyl pyrrolidone (PVP K90, molecular weight is about 130 ten thousand), and the oxidant is Ammonium Persulfate (APS) and/or potassium persulfate (KPS). Wherein, in the embodiment 7-8, the mass ratio of the oxidant (APS) to the oxidant (KPS) is 1: 1; in examples 9 to 11, the mass ratio of the hydrophilic monomer (NVP) and the hydrophilic polymer (PVP K90) in the solution was 1: 1.

The preparation process is as follows.

Dissolving PVP and NVP in absolute ethyl alcohol respectively, and obtaining PVP and NVP solutions respectively after shaking and uniform mixing. And respectively dissolving APS and KPS in water, and uniformly mixing by oscillation to obtain APS and KPS solutions, wherein the mass concentrations of all the solutions are listed in Table 2.

The contact lens substrates prepared in examples 1-5 were immersed in an APS and/or KPS aqueous solution for 20 minutes and then immersed in a PVP and/or NVP solution for 20 minutes, followed by high temperature treatment (each reaction temperature is shown in table 2) to react the PVP and/or NVP diffused into the contact lens substrates. Finally, the prepared contact lens was hydrated in purified water at 80 ℃ for 5 hours to remove the residue. The contact lens was removed and sealed in a PP cup with a standard saline solution for 30 minutes of moist heat sterilization to obtain the final product.

TABLE 2

Note: the mass% in table 2 represents the mass concentration of the corresponding solution.

Comparative examples 1 to 5 preparation of comparative contact lenses

In these comparative examples, experiments were conducted with the contact lens substrate prepared in example 2. The hydrophilic monomer is vinyl pyrrolidone (NVP), the hydrophilic polymer is polyvinyl pyrrolidone (PVP K90, molecular weight is about 130 ten thousand), and the oxidant is Ammonium Persulfate (APS) and/or potassium persulfate (KPS). Wherein, the mass ratio of the oxidant (APS) to the oxidant (KPS) in comparative example 1 is 1: 1; in comparative examples 3 to 5, the mass ratio of the hydrophilic monomer (NVP) and the hydrophilic polymer (PVP K90) in the solution was 1: 1.

The specific preparation process was the same as in examples 6 to 12, except that the oxidant solution, the hydrophilic monomer solution, and the hydrophilic polymer solution used in these comparative examples were different in mass concentration and different in reaction temperature as shown in table 3 below.

TABLE 3

Note: the mass% in table 3 represents the mass concentration of the corresponding solution.

Test method

1. Moisture content test

In the present invention, the water content of the substrate and the medical device (particularly, contact lens) is tested according to the following method.

At room temperature,samples of the substrates or contact lenses prepared in examples 1 to 5, 6 to 12 and comparative examples 1 to 5 were equilibrated overnight in a standard phosphate buffer solution, taken out and blotted dry, and the mass in the hydrated state was recorded by means of a mass balance and was counted as m₁. Then, the sample is placed in a vacuum drying oven at 60 ℃ to be dried to constant weight, the sample is taken out and placed in a dryer, after cooling, the sample is weighed and the mass is recorded, and the mass is m₂. The water content of the sample was calculated according to equation 1. The test results are shown in Table 4.

2. Static Water contact Angle test

In the present invention, the static water contact angles of the substrate and medical device (particularly contact lenses) are tested according to the following method. The static water contact angle can reflect the hydrophilicity of the surfaces of substrates and medical devices, particularly contact lenses.

At room temperature, 2. mu.l of the standard salt solution was dropped on the surfaces of the substrate or contact lens samples prepared in examples 1 to 5, 6 to 12 and comparative examples 1 to 5, and the samples were tested for static water contact angle using a static contact angle tester (model: JGW-360A). The test results are shown in Table 4.

3. Lubricity and coefficient of friction (CCOF) test

In the present invention, lubricity and coefficient of friction (CCOF) tests of substrates and medical devices, particularly contact lenses, were carried out according to the test methods in example 1 and example 29 of chinese patent (CN103293707B), respectively, and the test results are shown in table 4.

And (3) lubricity test: the substrate or contact lens samples prepared in examples 1-5, examples 6-12, and comparative examples 1-5 were rinsed with purified water at least 3 times and then transferred to a PBS solution (phosphate buffered saline) for at least 3 hours. The sample was rubbed between the fingers to feel lubricity.

Wherein the class 1 lubricity is defined as the lubricity of the oil in combination with Oasys^TMThe same lubricity as for contact lenses, class 4 lubricity being defined as Air Optix^TMThe same lubricity of contact lenses. If the sample lubricity is better than Air Optix^TMA contact lens is defined as grade 3, whereas if the sample lubricity is worse than Air Optix^TMContact lenses are defined as grade 5. Similarly, if the sample lubricity is better than Oasys^TMContact lenses are defined as grade 0, whereas if the sample lubricity is worse than Oasys^TMThe contact lens is defined as class 2.

Coefficient of friction (CCOF) test: the substrates or contact lens samples prepared in examples 1-5, examples 6-12, and comparative examples 1-5 were placed in a PBS solution for at least 6 hours. The glass plate was rinsed with soap solution and then rinsed in DI water for about 2 minutes. The glass plate was placed on pads of various heights of the plastic reservoir and the height of the plane was measured with a micrometer. The reservoir was filled with PBS solution to ensure complete submersion of the sample. The sample was placed on the "start line" and a 0.79g loop was dropped onto the sample surface. The time it took for the sample to travel 96mm was recorded as it slid down the plate. The repetition is carried out 3 times, and the friction coefficient of the sample is obtained by calculating the tangent function value of the critical angle theta.

4. Hydrophilic Polymer content test

In the present invention, the content of the hydrophilic polymer in the medical device (particularly, contact lens) is tested according to the following method.

Experimental groups:

at room temperature, the contact lens substrates prepared in examples 1 to 5 were respectively placed in a standard phosphate buffer solution to be balanced overnight, then transferred to a vacuum drying oven at 60 ℃ to be dried to constant weight, the samples were taken out and placed in a dryer, and after cooling, the total dry mass of each substrate was respectively weighed and recorded, and the total dry mass was m₁. Subsequently, the substrates were subjected to the conditions of the corresponding parameters shown in tables 2 and 3 to prepare contact lens samples of examples 6 to 12 and comparative examples 1 to 5.

Taking out all contact lens samples from the PP cups, placing the samples in a vacuum drying oven at 60 ℃ for drying until the samples are constant in weight, weighing and recording the total dry mass of the contact lenses after cooling in a dryer, wherein the total dry mass is m₂. The sample weight gain was calculated according to equation 2. Because of the small mass of the substrate and contact lens, the experiment has been carried outThe tests were all 20 pieces in one group.

Blank control group:

it should be noted that, since the sample may be dissolved out with the loss of the chain segment of the substrate during the soaking process of the oxidant solution and the hydrophilic monomer and/or hydrophilic polymer solution, and during the chemical crosslinking reaction, the blank control group is required to be used for the content test of the hydrophilic polymer fixed in the lens. The blank control sample was treated in the same manner as the test group except that the hydrophilic monomer and/or hydrophilic polymer solution was replaced with the pure solvent used in the solution, and the weight gain of the sample was calculated according to equation 2, in the same manner as the test group. The final hydrophilic polymer content (mass%) fixed in the lens is the weight gain of the experimental group sample minus the weight gain of the blank control group sample. The test results are shown in Table 4.

TABLE 4

The results show that the mass concentration or reaction temperature of the hydrophilic monomer solution, the hydrophilic polymer solution or the oxidant solution of the contact lenses prepared in comparative examples 1-5 is out of the range of the present invention, so that the static water contact angle and the friction coefficient are far higher than those of examples 6-12, the hydrophilicity is poor, the surface is rough, the lubricity is 4 grade and far lower than those of examples 6-12, and the content of the hydrophilic polymer is far lower than those of examples 6-12.

5. Surface element content test

The test method shows the change in atomic concentration at the surface of a contact lens sample as compared to the surface of a substrate after immobilizing a hydrophilic polymer in the contact lens substrate. An X-ray photoelectron spectrometer (model: Thermo ESCALAB 250) was used to perform the test under ultra-high vacuum using K.alpha.rays from an Al target as a detection source, and the results are shown in Table 5 below.

TABLE 5

Sample (I)	O	N	C	K	Si	Ca	S
								Example 2	21.73	3.31	64.85	0.32	9.28	0.04	0.46
Example 8	18.20	6.64	68.08	0.25	6.50	0.06	0.27

Note: the atomic concentrations (%) of the surfaces of the respective samples are shown in Table 5.

The results showed that the nitrogen content of the contact lens sample surface increased from 3.31% to 6.64% of the sample surface, while the silicon content of the exposed contact lens sample surface decreased from 9.28% to 6.5% of the substrate surface, indicating that the contact lens sample surface was covered with a large amount of polyvinylpyrrolidone (PVP).

6. Hydrophilic polymer sustained release rate alpha test

The test method measures the length of time the hydrophilic polymer remains on the contact lens to assess the durability of the surface property improvement after treatment of the contact lens substrate.

The hydrophilic polymer release rate α is defined as the release rate of the hydrophilic polymer when the contact lens is immersed in a standard phosphate solution at 37 ℃ for 1 year.

The test was conducted using the contact lens sample of example 8, where the hydrophilic polymer was polyvinylpyrrolidone (PVP) and thus α ═ m in example 8_{Dissolved PVP}/m _{Fixed PVP}100%. The amount of PVP eluted from the contact lens samples was calculated by subtracting the difference in PVP content in standard phosphate solutions using liquid chromatography. The results are shown in Table 6 below.

TABLE 6

The result shows that the slow release rate of the hydrophilic polymer fixed in the contact lens sample is extremely low, the slow release rate alpha of the hydrophilic polymer after being soaked in a standard salt solution for 1 year at 37 ℃ is 0.09 percent, and the slow release rate alpha of the hydrophilic polymer after being soaked in an isopropanol solvent for 120 hours is 0.11 percent, so that the hydrophilic polymer is firmly combined with the substrate and is not easy to precipitate.

7. Glass transition temperature and melting point testing

Model number Q20 manufactured by TA instruments of AmericaThe melting point (T) of the contact lens sample and the corresponding substrate is calculated and analyzed_m) And glass transition temperature (T)_g) The results are shown in Table 7.

TABLE 7

Sample (I)	Glass transition temperature (T)_g)	Melting Point (T)_m)
			Example 2	44.23℃	128.97℃
Example 8	44.39℃	133.13℃

As can be seen from Table 7, the contact lenses treated with the hydrophilic polymer had higher melting points and glass transition temperatures.

Industrial applicability

The medical devices of the invention, particularly contact lenses, can be used in a wide variety of consumer medical and everyday applications.

Claims

1. A medical device having a substrate, and a hydrophilic polymer immobilized on the substrate by chemical cross-linking, characterized in that the chemical cross-linking occurs between alkyl chain radical active sites of the hydrophilic polymer and/or between alkyl chain radical active sites of the hydrophilic polymer and radical active sites of the substrate; these free radical reactive sites are generated by the reaction of an oxidizing agent with the hydrophilic polymer and/or substrate material.

2. Medical device according to claim 1, characterized in that the hydrophilic polymer fixed to the substrate is present in an amount of 0.1 to 20% by mass, preferably 5 to 15% by mass, based on the total dry mass of the substrate.

3. The medical device according to claim 1, wherein the hydrophilic polymer is selected from one or more of hydrophilic polymers containing cyclic amide or cyclic imine structures in the backbone, poly-N, N-dimethylacrylamide, polyvinyl alcohol, polyethylene glycol, polyacrylic acid, polyethylene oxide, poly-2-ethyl-oxazoline, polymers containing phosphorylcholine vinyl monomers, and polysaccharides, preferably from the group consisting of polyvinylpyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-piperidone, poly-N-vinyl-2-piperidone, poly-N, N-vinyl-2-piperidone, poly-2-methyl-and poly-N-amide, One or more of poly N-vinyl-4-methyl-2-caprolactam, poly N-vinyl-3-ethyl-2-pyrrolidone, poly N-vinyl-4, 5-dimethyl-2-pyrrolidone and polyvinyl imidazole.

4. The medical device according to claim 1, characterized in that the weight average molecular weight of the hydrophilic polymer is 50000 or more, preferably 50000 to 1500000, more preferably 200000 to 1500000.

5. The medical device according to claim 1, characterized in that the oxidizing agent is selected from one or more of peroxides or per-sulfides, preferably one or more of hydrogen peroxide, potassium persulfate, sodium persulfate, ammonium persulfate.

6. A medical device according to any of claims 1-5, characterized in that it satisfies at least one of the following characteristics:

7. A medical device according to any of claims 1 to 6, wherein the medical device is a contact lens and the substrate is a contact lens substrate, preferably a silicone hydrogel contact lens substrate.

8. The medical device according to any one of claims 1 to 7, wherein the substrate is made of a material obtained by copolymerizing at least a silicon-containing monomer and/or a prepolymer of a silicon-containing monomer and a hydrophilic monomer at a mass ratio of the silicon-containing monomer and/or the prepolymer of a silicon-containing monomer to the hydrophilic monomer, that is, the ratio of the silicon-containing monomer and/or the prepolymer of a silicon-containing monomer: the mass ratio of the hydrophilic monomer is (40-70) to (30-60); preferably, the substrate material further comprises a diluent; more preferably, the diluent is a solvent and/or a hydrophilic polymer.

9. The medical device according to claim 8, characterized in that the silicon-containing monomer and/or prepolymer of silicon-containing monomer is selected from one or more of mono-or di-terminated acryloxy or methacryloxy and acrylamido or methacrylamido terminated silicone monomers, and/or acryloxy or methacryloxy and acrylamido or methacrylamido mono-or di-terminated polysiloxanes;

10. A method of manufacturing a medical device according to any one of claims 1 to 9, comprising: manufacturing a substrate, immersing the substrate in a solution containing the hydrophilic polymer and/or the hydrophilic monomer and an oxidizing agent, followed by a chemical reaction, thereby manufacturing the medical device.

11. The method according to claim 10, wherein the chemical reaction is a chemical crosslinking reaction, and the temperature of the chemical reaction is 20 to 200 ℃, preferably 50 to 150 ℃, and more preferably 70 to 120 ℃.

12. The method according to any one of claims 10 to 11, wherein immersing the substrate in a solution containing the hydrophilic polymer and/or the hydrophilic monomer and the oxidizing agent comprises: simultaneously adding the hydrophilic polymer and/or the hydrophilic monomer and the oxidant into a solvent to form a mixed solution, and then soaking the substrate in the mixed solution; or, respectively dissolving the hydrophilic polymer and/or the hydrophilic monomer and the oxidant in a solvent, and then soaking the substrate in the hydrophilic polymer solution and/or the hydrophilic monomer solution and the oxidant solution respectively;