CN111744055A

CN111744055A - Hydrophilic implant product and preparation method thereof

Info

Publication number: CN111744055A
Application number: CN202010605202.4A
Authority: CN
Inventors: 金明君
Original assignee: Beijing Xingyun Zhongyu Technology Co ltd
Current assignee: Beijing Xingyun Zhongyu Technology Co ltd
Priority date: 2020-06-29
Filing date: 2020-06-29
Publication date: 2020-10-09

Abstract

The invention provides a hydrophilic implant product and a preparation method thereof. The hydrophilic implant product comprises an implant body and a hydrophilic layer, wherein the surface of the implant body is a hydrophilic surface, the hydrophilic layer is a coating layer of a water-soluble chitosan derivative or an attachment film with the water-soluble chitosan derivative, the attachment film is an attachment film formed by attaching an aqueous solution of the water-soluble chitosan derivative to the surface of the implant body, and the substitution degree of the water-soluble chitosan derivative is 0.6-1.9. The hydrophilic layer with the water-soluble chitosan derivative is arranged on the implant body of the hydrophilic implant product, the hydrophilic property of the water-soluble chitosan derivative is utilized to keep the hydrophilicity of the implant, and the sealing operation is not needed, so that the hydrophilic implant product is simple to manufacture and easy to operate. When the degree of substitution of the water-soluble chitosan derivative is 0.6 to 1.9, the water-soluble chitosan derivative is preferably hydrophilic. The water-soluble chitosan derivative also has biological functions and good biocompatibility.

Description

Hydrophilic implant product and preparation method thereof

Technical Field

The invention relates to the field of implant modification, in particular to a hydrophilic implant product and a preparation method thereof.

Background

The oral implant is an artificial tooth root used for repairing a missing tooth, and is implanted into the missing tooth area of a jaw bone in a surgical mode. The osseointegration between the implant and the alveolar bone refers to the mechanical integration between the surface of the implant and the new bone without soft tissue intervention. Currently, most oral implant surfaces are hydrophobic, only a small fraction being hydrophilic. The average osseointegration rate of hydrophilic surfaces is significantly faster than that of hydrophobic surfaces when the implant surface physical morphology (including average surface roughness, surface uniformity, surface cleanliness) is otherwise identical. The surface treatment of the implant is a main core technology in the aspects of improving the success rate of the implant, shortening the treatment period and the like.

The implant surface treatment technology is a technology for accelerating the generation of osseointegration on the surface of an implant which is simply machined by physical, chemical, biological and other methods.

According to the form and characteristics of the implant surface, the implant surface treatment techniques can be classified into the following categories:

(one), uncoated rough implant surface (hydrophobic)

The original implant surface just produced is hydrophilic, but becomes hydrophobic after being contaminated by carbon elements in the air, so most uncoated rough implant surfaces are hydrophobic. Such implant surfaces are intended to improve the stability (retention) of the implant and shorten the treatment period, mainly by increasing the implant surface area (increasing the bone contact area). For example, SLA (large particle blasting followed by acid etching) surfaces, where relatively smooth original implant surfaces are blasted with alumina particles and then acid-etched with a strong acid to roughen the implant surface. Other more common uncoated rough surfaces are: RBM (hydroxyapatite blasting) surfaces, OSSEOTITE (double acid etching) surfaces, TiUnite (anodic oxidation) surfaces, etc.

(II) chemical coating of implant surface (hydrophobicity)

For example, a method of forming a chemical coating having a certain thickness by spraying powder containing hydroxyapatite as a main component onto the surface of an implant in a high-temperature molten state on the surface of HA (hydroxyapatite coating). Other more common chemical coating surfaces are: NANOTEE (crystal deposition treatment surface, further performing deposition treatment of nano-scale calcium phosphate crystal on the basis of double acid etching treatment surface), and the like. Such surfaces, which are typically dry in morphology, have surface chemistries associated with promoting osseointegration (e.g., hydroxyapatite, tricalcium phosphate, calcium carbonate crystals, etc.).

(III) common hydrophilic implant surface

The following method is used in U.S. Pat. No. US6702855B 1: the implant surface treatment is carried out under the inert gas environment (such as nitrogen), so that the original implant surface which is originally hydrophilic is prevented from contacting with air and becoming a hydrophobic surface. Then soaking the hydrophilic surface implant which is not polluted by the air into an ionic solution (such as a sodium chloride aqueous solution) with a certain concentration for sealing so as to maintain the hydrophilic characteristic of the implant surface.

However, since the hydrophilic implant uses an inert gas and an ionic solution to protect the surface of the implant, the implant needs to be strictly sealed, which results in a complicated process and a high difficulty in operation.

Disclosure of Invention

The invention mainly aims to provide a hydrophilic implant product and a preparation method thereof, and aims to solve the problems of complex process and difficult operation of a hydrophilic implant in the prior art.

In order to achieve the above object, according to one aspect of the present invention, there is provided a hydrophilic implant product comprising an implant body and a hydrophilic layer, wherein the surface of the implant body is a hydrophilic surface, the hydrophilic layer is a coating layer of a water-soluble chitosan derivative or an attachment film having a water-soluble chitosan derivative, the attachment film is an attachment film in which an aqueous solution of the water-soluble chitosan derivative is attached to the surface of the implant body, and the substitution degree of the water-soluble chitosan derivative is 0.6 to 1.9.

Further, the hydrophilic layer is a coating layer, and the thickness of the coating layer is preferably 10nm to 150 μm.

Further, the hydrophilic layer is an attachment film with a water-soluble chitosan derivative, the hydrophilic implant product further comprises an aqueous solution of the water-soluble chitosan derivative, the aqueous solution forms the attachment film on the implant body, and the mass fraction of the water-soluble chitosan derivative in the aqueous solution is preferably 1-4%.

Further, the water-soluble chitosan derivative is one or more of carboxylated chitosan, chitosan salts, chitosan sulfate, chitosan oligosaccharide and hyaluronic acid-like chitosan, preferably carboxylated chitosan is carboxymethyl chitosan, carboxyethyl chitosan and carboxypropyl chitosan, and preferably chitosan salts are chitosan hydrochloride, chitosan quaternary ammonium salt, chitosan lactate and chitosan glutamate.

Further, the carboxymethyl chitosan is N, O-carboxymethyl chitosan, and the substitution degree of the N, O-carboxymethyl chitosan is preferably 0.6 to 1.9.

According to another aspect of the present invention, there is provided a method of preparing a hydrophilic implant product according to any one of the above, the method comprising: carrying out ultraviolet treatment on the raw material implant body to obtain an implant body, wherein the surface of the implant body is a hydrophilic surface; coating a water-soluble chitosan derivative coating on the implant body or soaking the implant body in an aqueous solution of the water-soluble chitosan derivative to obtain a hydrophilic implant product.

Further, the wavelength of the ultraviolet ray used for the ultraviolet ray treatment is 150 to 300nm, preferably 180 to 254 nm.

Further, the ultraviolet ray irradiation intensity is 15-1000 mW/cm in the ultraviolet ray treatment²Preferably 24-200 mW/cm²。

Further, in the ultraviolet treatment, the irradiation time of the ultraviolet ray is 1 to 90min, preferably 60 to 90 min.

Further, the temperature of the aqueous solution of the water-soluble chitosan derivative is 10 to 45 ℃ during the soaking.

By applying the technical scheme of the invention, the hydrophilic layer with the water-soluble chitosan derivative is arranged on the implant body of the hydrophilic implant product, the hydrophilic property of the water-soluble chitosan derivative is utilized to ensure that the implant keeps hydrophilic, and the sealing operation is not needed, so that the hydrophilic implant product is simple to manufacture and easy to operate. When the degree of substitution of the water-soluble chitosan derivative is 0.6 to 1.9, the water-soluble chitosan derivative is preferably hydrophilic. The water-soluble chitosan derivative also has biological functions, and mainly has the functions of stopping bleeding, inhibiting bacteria, relieving pain, healing wound, promoting osteoblast growth and the like. Meanwhile, the water-soluble chitosan derivative can be completely degraded in vivo, and has no toxicity, immunogenicity, tissue irritation and biocompatibility.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the invention and, together with the description, serve to explain the invention and not to limit the invention. In the drawings:

fig. 1 is a view showing the result of blood movement in an implant according to embodiment 1 of the present invention;

fig. 2 is a view showing the result of blood movement in the implant of comparative example 1 of the present invention.

Detailed Description

It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail below with reference to the embodiments with reference to the attached drawings.

Interpretation of terms:

oral implant: when the artificial tooth root is used for repairing the missing tooth, the artificial tooth root is implanted into the missing tooth area of a jaw bone in a surgical mode.

Osseointegration: the implant surface and the new bone are mechanically combined without soft tissue intervention.

The implant surface treatment technology comprises the following steps: the technology of the osseointegration can be generated on the surface of the implant which is simply machined by physical, chemical, biological and other methods as soon as possible. For example, a smooth machined surface is changed to a rough surface or a hydrophobic surface is changed to a hydrophilic surface, etc.

Hydrophilicity: the molecules with polar groups have strong affinity to water and can attract water molecules, and the surfaces of the solid materials are easy to be wetted by water.

Hydrophobicity: hydrophobic molecules are biased to be non-polar, and generally gather together in water, while water forms a large contact angle and is in the form of drops on a hydrophobic surface.

Implant stability (retention force): is the sum of the implant primary stability (the mechanical retention force generated between the implant thread and the alveolar bone at the initial stage of implantation) and the implant secondary stability (the biological retention force generated between the implant surface and the alveolar bone with the formation of new bone).

As analyzed in the background of the present application, the prior art technique of maintaining the hydrophilic property in a sealing manner is complicated and difficult to operate practically, and in order to solve this problem, the present application provides a hydrophilic implant product and a method for preparing the same.

In an exemplary embodiment of the present application, a hydrophilic implant product is provided, which includes an implant body and a hydrophilic layer, wherein the surface of the implant body is a hydrophilic surface, the hydrophilic layer is a coating layer of a water-soluble chitosan derivative or an attachment film with a water-soluble chitosan derivative, the attachment film is an attachment film in which an aqueous solution of the water-soluble chitosan derivative is attached to the surface of the implant body, and a substitution degree of the water-soluble chitosan derivative is 0.6 to 1.9.

The hydrophilic implant product is provided with the hydrophilic layer with the water-soluble chitosan derivative on the implant body, the hydrophilic characteristic of the water-soluble chitosan derivative is utilized to enable the implant to keep hydrophilic, and sealing operation is not needed, so that the hydrophilic implant product is simple to manufacture and easy to operate. When the degree of substitution of the water-soluble chitosan derivative is 0.6 to 1.9, the water-soluble chitosan derivative is preferably hydrophilic. The water-soluble chitosan derivative also has biological functions, and mainly has the functions of stopping bleeding, inhibiting bacteria, relieving pain, healing wound, promoting osteoblast growth and the like. Meanwhile, the water-soluble chitosan derivative can be completely degraded in vivo, and has no toxicity, immunogenicity, tissue irritation and biocompatibility.

When the hydrophilic layer is a coating, the thickness of the coating is preferably 10nm to 150 μm in order to ensure sufficient hydrophilicity, to ensure strength of the implant body, and to prevent the coating from falling off due to excessive thickness.

In order to maintain the quality and hydrophilic quality of the hydrophilic implant product for a long period of time, it is preferable that the hydrophilic layer is an attachment film having a water-soluble chitosan derivative, and the hydrophilic implant product further includes an aqueous solution of the water-soluble chitosan derivative, the aqueous solution forming the attachment film on the implant body. On the basis of forming a water-soluble chitosan derivative with sufficient concentration by using an aqueous solution, in order to avoid the waste of the water-soluble chitosan due to excessive concentration caused by excessive water-soluble chitosan derivative and excessive solution viscosity, the mass fraction of the water-soluble chitosan derivative in the aqueous solution is preferably 1-4%.

The presence of the water-soluble chitosan derivative as a coating is preferable to the presence of a film because the flocculation phenomenon may occur when the aqueous solution of the water-soluble chitosan derivative is at a temperature below zero degrees celsius, so that the uniform distribution of the water-soluble chitosan derivative in the aqueous solution may be affected by the non-uniform distribution of the water-soluble chitosan derivative on the surface of the implant, and the coating does not have this problem.

The water-soluble chitosan derivative used in the present application may be a water-soluble chitosan derivative commonly used in the medical field, for example, the water-soluble chitosan derivative is any one or more of carboxylated chitosan, chitosan salts, chitosan sulfate, chitosan oligosaccharide, and hyaluronic acid-like chitosan. To further improve the safety, preferably the carboxylated chitosan is carboxymethyl chitosan, carboxyethyl chitosan and carboxypropyl chitosan. The chitosan salt is chitosan hydrochloride, chitosan quaternary ammonium salt, chitosan lactate and chitosan glutamate.

The carboxymethyl chitosan is preferably N, O-carboxymethyl chitosan, more preferably N, O-carboxymethyl chitosan with a degree of substitution of 0.6 to 1.9, even more preferably 0.6 to 1.5.

In general, N, O-carboxymethyl chitosan is insoluble at pH 2 to 6, and is soluble at other pH. The pH value in blood generally varies from 7.35 to 7.45. Therefore, the N, O-carboxymethyl chitosan can be dissolved in blood. The preparation requirement of the O-carboxymethyl chitosan is relatively high, such as reaction temperature and the like, and specifically: the solubility of O-carboxymethyl chitosan is closely related to the dissolution conditions, O-carboxymethyl chitosan prepared under the action of chitosan and chloroacetic acid at 0-20 ℃ is soluble in all pH ranges, and O-carboxymethyl chitosan prepared at the reaction temperature higher than 20 ℃ has an insoluble region when the pH is about 7. Therefore, the preparation conditions of O-carboxymethyl chitosan are relatively harsh, so that O-carboxymethyl chitosan is not preferred. The prepared O-carboxymethyl chitosan is almost the same as N, O-carboxymethyl chitosan in biological function in all aspects according to a specific temperature (a proper temperature not higher than 20 ℃). Therefore, although not preferred, it can also be used to make coatings. N-carboxymethyl chitosan, which has an influence on the ratio of monocyte/macrophage, and thus on T cell proliferation, and INF-gamma cell production, is preferred to N, O-carboxymethyl chitosan, because of its simplicity of preparation and biosafety.

In another exemplary embodiment of the present application, there is provided a method of preparing a hydrophilic implant product according to any one of the above, the method comprising: carrying out ultraviolet treatment on the raw material implant body to obtain an implant body, wherein the surface of the implant body is a hydrophilic surface; coating a water-soluble chitosan derivative coating on the implant body or soaking the implant body in an aqueous solution of the water-soluble chitosan derivative to obtain a hydrophilic implant product.

By utilizing the preparation method, the surface of the raw material implant body is endowed with a hydrophilic function by ultraviolet irradiation, and meanwhile, the function of cleaning impurities on the surface of the implant is also realized, so that the cleanliness of the surface of the implant is improved, and a subsequently formed hydrophilic layer is firmly attached; set up hydrophilic layer through the mode of coating or soaking on planting the body, the thickness of hydrophilic layer that the coating mode formed is comparatively even, and the mode that the mode of soaking formed hydrophilic layer is comparatively convenient. The hydrophilic layer with the water-soluble chitosan derivative is arranged on the implant body, the hydrophilic property of the water-soluble chitosan derivative is utilized to keep the implant hydrophilic, and the sealing operation is not needed, so that the hydrophilic implant product is simple to manufacture and easy to operate. When the degree of substitution of the water-soluble chitosan derivative is 0.6 to 1.9, the water-soluble chitosan derivative has better hydrophilicity. The water-soluble chitosan derivative also has biological functions, and mainly has the functions of stopping bleeding, inhibiting bacteria, relieving pain, healing wound, promoting osteoblast growth and the like. Meanwhile, the water-soluble chitosan derivative can be completely degraded in vivo, and has no toxicity, immunogenicity, tissue irritation and biocompatibility.

Compared with the soaking mode, the mode of arranging the coating is preferably the coating because the flocculation phenomenon is likely to occur when the water solution of the water-soluble chitosan derivative is lower than zero centigrade, so that the uniform distribution of the water-soluble chitosan derivative in the water solution is influenced due to the nonuniform distribution of the water-soluble chitosan derivative, and the coating does not have the problem.

When the raw material implant body is subjected to ultraviolet treatment, the ultraviolet wavelength, the ultraviolet irradiation intensity and the ultraviolet irradiation time can all refer to the prior art.

In a preferred embodiment, the wavelength of the ultraviolet light used for the ultraviolet light treatment is 150 to 300nm, preferably 180 to 254 nm. Under the irradiation of ultraviolet rays in the wavelength range, the hydrophilization reaction generated on the surface of the implant body is most active, and the method is more favorable for removing a pollution source on the surface of the implant which changes the surface of the raw material implant into hydrophobic, thereby forming a hydrophilic surface.

In another preferred embodiment, the ultraviolet ray treatment is carried out at an irradiation intensity of 15 to 1000mW/cm²Preferably 24-200 mW/cm². Under the irradiation of ultraviolet rays within the irradiation intensity range, the hydrophilization reaction generated on the surface of the implant body is most active, and the method is more favorable for removing a pollution source on the surface of the implant body which changes the surface of the raw material implant into hydrophobic, thereby forming a hydrophilic surface.

In another preferred embodiment, the ultraviolet irradiation time is 1 to 90min, preferably 60 to 90 min. The longer the ultraviolet irradiation time is, the more thorough the contamination removal is, and the better the surface hydrophilicity is. When the ultraviolet rays with the wavelength and the irradiation intensity are used for irradiating for 60min to 90min, the surface contact angle is less than 5 degrees. The smaller the contact angle of a water droplet on the implant surface, the better the hydrophilicity is indicated.

In order to improve the uniformity of the hydrophilic layer, it is preferable that the temperature of the aqueous solution of the water-soluble chitosan derivative is adjusted to 10 to 45 ℃ during the immersion.

The advantageous effects of the present application will be further described below with reference to examples and comparative examples.

Example 1

Comparison of N, O-carboxymethyl chitosan coated surface to glucose coated surface with respect to the degree of protein attachment:

the materials or articles used in this example are as follows: shinuokang AF +4310 implant (raw material implant without coating hydrophobic surface) and N, O-carboxymethyl chitosan aqueous solution.

The apparatus used in this example was as follows:

the product name of the ultraviolet irradiation device used is AC-6; the product name of the mixer used is HR-200; the drying apparatus used has a product name WOF-W105 and the caliper has a product name Elcometer-F1.

Hydrophilization pretreatment (UV irradiation): inserting the Shinuokang AF +4310 implant into the positioner, and then placing the positioner inserted with the implant into the ultraviolet irradiation device. At a wavelength of 182nm, 56mW/cm²The irradiation intensity of (2) was 60 minutes to obtain an implant body having a hydrophilic surface. And (3) soaking the implant body obtained after the hydrophilization pretreatment (UV irradiation) into an N, O-carboxymethyl chitosan aqueous solution with the substitution degree of 0.6 and the mass fraction of 2%. The temperature of the aqueous solution at this time was set to 37 ℃ and stirring was carried out at 680rpm for 10 minutes.

And taking the implant out of the solution, and drying the implant for 3 hours at the temperature of 40 ℃ by using a drying device to finish the preparation of the N, O-carboxymethyl chitosan coating, wherein the thickness of the N, O-carboxymethyl chitosan coating is between 35 and 40 mu m.

Example 2

The difference from example 1 is that N, O-carboxymethyl chitosan coating was prepared using an N, O-carboxymethyl chitosan aqueous solution having a substitution degree of 1.5 and a mass fraction of 2%, wherein after the implant was taken out of the solution, it was dried at 40 ℃ for 3.3 hours using a drying apparatus, and the preparation of N, O-carboxymethyl chitosan coating was completed, and the thickness of the N, O-carboxymethyl chitosan coating was between 35 μm and 40 μm.

Example 3

The difference from example 1 is that N, O-carboxymethyl chitosan coating was prepared using an N, O-carboxymethyl chitosan aqueous solution having a substitution degree of 1.9 and a mass fraction of 2%, wherein after the implant was taken out of the solution, it was dried at 40 ℃ for 3.5 hours using a drying apparatus, and the preparation of N, O-carboxymethyl chitosan coating was completed, and the thickness of the N, O-carboxymethyl chitosan coating was between 35 μm and 40 μm.

Example 4

The difference from the embodiment 1 is that the O-carboxymethyl chitosan coating is prepared by adopting an O-carboxymethyl chitosan aqueous solution with the substitution degree of 0.6 and the mass fraction of 2 percent, and the thickness of the O-carboxymethyl chitosan coating is between 35 and 40 mu m.

Example 5

The difference from example 1 is that an N-carboxymethyl chitosan coating was prepared using an N-carboxymethyl chitosan aqueous solution having a degree of substitution of 0.6 and a mass fraction of 2%, wherein the N-carboxymethyl chitosan coating was prepared by taking the implant out of the solution and drying the implant at 40 ℃ for 3.5 hours using a drying apparatus, and the thickness of the N-carboxymethyl chitosan coating was between 35 μm and 40 μm.

Example 6

Preparing 2 percent of N, O-carboxyethyl chitosan aqueous solution by mass fraction. An aqueous solution prepared by mixing 2g of N, O-carboxyethyl chitosan having a degree of substitution of 0.6 with 98g of distilled water in a mass fraction of 2% exhibited a slightly uneven turbid liquid state.

Neutral aqueous solutions were prepared using N, O-carboxyethyl chitosan with degrees of substitution of 0.5, 0.55, 0.58, 0.6, 0.65, 0.68, 0.7, 0.75, 0.78, 0.8, 0.85, 0.88. As a result, it was found that when the degree of substitution was 0.5, 0.55, 0.58, a significantly uneven turbid state was exhibited; when the degree of substitution is 0.6, 0.65, 0.68, 0.7, 0.75, 0.78, 0.8, a slightly uneven turbid state is exhibited; n, O-carboxyethyl chitosan with a degree of substitution greater than 0.8 is initially completely soluble in distilled water. The larger the substitution degree of the N, O-carboxyethyl chitosan is, the better the water solubility is; under the same substitution degree, the water solubility of the N, O-carboxymethyl chitosan is superior to that of the N, O-carboxyethyl chitosan. N, O-carboxyethyl chitosan having a degree of substitution in the range of 0.6 to 0.8 is also suitable for use in the present invention, but is not preferred because the effect is slightly reduced as compared with N, O-carboxyethyl chitosan having a degree of substitution of more than 0.8.

Example 7

The difference from the example 1 is that the chitosan hydrochloride coating is made by adopting the chitosan hydrochloride aqueous solution with the substitution degree of 0.6 and the mass fraction of 2 percent, and the thickness of the chitosan hydrochloride coating is between 27 and 32 mu m.

Example 8

The difference from the example 1 is that the N, O-carboxymethyl chitosan coating is prepared by adopting the N, O-carboxymethyl chitosan aqueous solution with the substitution degree of 0.6 and the mass fraction of 1 percent, and the thickness of the N, O-carboxymethyl chitosan coating is between 18 and 23 mu m.

Example 9

The difference from the example 1 is that the N, O-carboxymethyl chitosan coating is prepared by adopting N, O-carboxymethyl chitosan aqueous solution with the substitution degree of 0.6 and the mass fraction of 4 percent, and the thickness of the N, O-carboxymethyl chitosan coating is between 51 and 56 mu m.

From 40 μm, the exfoliation was increased with increasing thickness. The main manifestation is that when the implant is implanted into the alveolar bone with thick cortical bone and hard bone, the probability of exfoliation between the coating on the surface of the implant and the implant is increased. Therefore, 35 μm to 40 μm in example 1 is a more desirable coating thickness, which ensures a sufficient amount of the effective ingredient and also reduces the possibility of the coating peeling off when the implant is implanted into the alveolar bone to some extent. However, coatings having a thickness in the range of 40 μm to 150 μm may also be used, but the range of indications is limited, and are more suitable for cases where the bone mass is relatively soft, such as the posterior maxillary dental area, because the soft bone mass reduces the probability of coating exfoliation.

Example 10

The difference from example 1 is that the aqueous solution of N, O-carboxymethyl chitosan having a degree of substitution of 0.6 and a mass fraction of 5% exhibits a non-uniform turbid liquid state, not a uniform transparent solution state.

Example 11

The difference from example 1 is that the ultraviolet treatment conditions were: at a wavelength of 300nm, 15mW/cm²The irradiation intensity of (2) is 90 minutes, and an implant body with a hydrophilic surface is obtained.

The contact angle of the water droplet was almost the same as that of example 1, and it was found that the effect of the hydrophilization pretreatment was almost the same at about 5 degrees. The wavelength has the most reactivity in the range of 150-300 nm, so compared with the embodiment 1, the wavelengths are all in the range with higher reactivity, and no obvious difference exists; although the irradiation intensity was lower than that in example 1, the irradiation time was extended by 30 minutes, and the effect of the final hydrophilization pretreatment was almost the same.

Example 12

The difference from example 1 is that the ultraviolet treatment conditions were: at a wavelength of 250nm, 24mW/cm²The irradiation intensity of (2) is 90 minutes, and an implant body with a hydrophilic surface is obtained.

Example 13

The difference from example 1 is that the ultraviolet treatment conditions were: at a wavelength of 150nm, 1000mW/cm²The irradiation intensity of (2) was 50 minutes to obtain an implant body having a hydrophilic surface.

The contact angle of the water droplet was almost the same as that of example 1, and it was found that the effect of the hydrophilization pretreatment was almost the same at about 5 degrees. The wavelength has the most reactivity in the range of 150-300 nm, so compared with the embodiment 1, the wavelengths are all in the range with higher reactivity, and no obvious difference exists; although the irradiation time was reduced by 10 minutes, the irradiation intensity was increased by about 17.85 times, and the effect of the hydrophilization pretreatment was limited, so that the final hydrophilization pretreatment effect was almost the same.

Example 14

The difference from example 1 is that the ultraviolet treatment conditions were: at a wavelength of 180nm, 200mW/cm²The irradiation intensity of (2) was 60 minutes to obtain an implant body having a hydrophilic surface.

The contact angle of the water droplet was almost the same as that of example 1, and it was found that the effect of the hydrophilization pretreatment was almost the same at about 5 degrees. The wavelength has the most reactivity in the range of 150-300 nm, so compared with the embodiment 1, the wavelengths are all in the range with higher reactivity, and no obvious difference exists; the irradiation time is the same; the irradiation intensity is enhanced by about 3.57 times. However, the effect of hydrophilic speech treatment is limited, so the same effect as in example 1 is achieved, but not significantly surpassed, and is almost the same.

Example 15

The difference from example 1 is that the ultraviolet treatment conditions were: at a wavelength of 220nm, 150mW/cm²The irradiation intensity of (2) is 90 minutes, and an implant body with a hydrophilic surface is obtained.

The contact angle of the water droplet was almost the same as that of example 1, and it was found that the effect of the hydrophilization pretreatment was almost the same at about 5 degrees. The wavelength has the most reactivity in the range of 150-300 nm, so compared with the embodiment 1, the wavelengths are all in the range with higher reactivity, and no obvious difference exists; the irradiation time is the same; the irradiation intensity is enhanced by about 2.67 times. However, the effect of hydrophilic speech treatment is limited, so the same effect as in example 1 is achieved, but not significantly surpassed, and is almost the same.

Comparative example 1

The same method as in example 1 was used to perform ultraviolet irradiation treatment on the Shinokang AF +4310 implant, and an implant body having a hydrophilic surface was obtained.

And soaking the implant body with the hydrophilic surface into the same 2% glucose aqueous solution by mass fraction. The temperature of the aqueous solution at this time was set to 37 ℃ and stirring was carried out at 680rpm for 10 minutes.

And taking the implant out of the solution, and drying the implant for 3 hours at the temperature of 40 ℃ by using a drying device to finish the preparation of the glucose coating, wherein the thickness of the glucose coating is between 30 and 35 mu m.

Comparative example 2

The difference from the example 1 is that the N, O-carboxymethyl chitosan coating is prepared by adopting the N, O-carboxymethyl chitosan aqueous solution with the substitution degree of 0.5 and the mass fraction of 2 percent, and the thickness of the N, O-carboxymethyl chitosan coating is between 35 and 40 mu m.

The implant with the coating in the example and the implant with the coating specifically in the comparative example were placed in a mixed solution of osteoblasts and physiological saline at a concentration of 12000 cells/100. mu.L, respectively. After 3.5 hours, the absorbance at 595nm was measured by crystal violet staining (crystal violet) using a special instrument for enzyme linked immunosorbent assay (ELISAreader). The higher the absorbance, the more favorable the N, O-carboxymethyl chitosan coating is for osteoblast aggregation and attachment, and it is also theorized that it is more favorable for promoting the osseointegration reaction between the implant and the bone tissue.

The implant with the water-soluble chitosan derivative coating surface and the implant with the glucose coating surface prepared in the examples and the comparative examples were immersed in a culture dish filled with blood in a zone with 4 pitches from the tip upward while being vertically downward, and were kept still. The higher the height of blood along the threaded automated plate within a defined time, the better the hydrophilicity of the implant surface. The experimental time was set to 15 seconds. After 15 seconds, each implant was observed for the number of pitches the blood came along the threaded disc and the number of pitches remaining, as noted in table 1.

TABLE 1

	Number of rising pitches	Number of residual pitches
			Example 1	7	2
Example 2	7.5	1.5
			Example 3	8	1
Example 4	7	2
			Example 5	7	2
Comparative example 1	4	5
			Comparative example 2	3	6

In addition, as shown in fig. 1, blood ascended a height of 7 pitches along the implant of example 1 having the N, O-carboxymethyl chitosan coating, and a height of 2 pitches remained. As shown in FIG. 2, blood was along the glucose-coated implant of comparative example 1 at a height of 4 pitches along the threaded disk, and at a height of 5 pitches remained.

From the above description, it can be seen that the above-described embodiments of the present invention achieve the following technical effects:

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The hydrophilic implant product is characterized by comprising an implant body and a hydrophilic layer, wherein the surface of the implant body is a hydrophilic surface, the hydrophilic layer is a coating layer of a water-soluble chitosan derivative or an attachment film with the water-soluble chitosan derivative, the attachment film is an attachment film attached to the surface of the implant body by an aqueous solution of the water-soluble chitosan derivative, and the substitution degree of the water-soluble chitosan derivative is 0.6-1.9.

2. The hydrophilic implant product of claim 1, wherein the hydrophilic layer is the coating, preferably the coating has a thickness of 10nm to 150 μ ι η.

3. The hydrophilic implant product according to claim 1, wherein the hydrophilic layer is an attachment film with a water-soluble chitosan derivative, the hydrophilic implant product further comprising an aqueous solution of a water-soluble chitosan derivative forming the attachment film on the implant body, preferably the mass fraction of the water-soluble chitosan derivative in the aqueous solution is 1-4%.

4. The hydrophilic implant product of claim 1, wherein the water soluble chitosan derivative is any one or more of carboxylated chitosan, chitosan salts, chitosan sulfate, chitosan oligosaccharide, hyaluronic acid-like chitosan, preferably the carboxylated chitosan is carboxymethyl chitosan, carboxyethyl chitosan and carboxypropyl chitosan, preferably the chitosan salts are chitosan hydrochloride, chitosan quaternary ammonium salt, chitosan lactate and chitosan glutamate.

5. The hydrophilic implant product of claim 4, wherein the carboxymethyl chitosan is N, O-carboxymethyl chitosan, preferably the degree of substitution of the N, O-carboxymethyl chitosan is 0.6 to 1.9.

6. A method of preparing the hydrophilic implant product of any one of claims 1 to 5, comprising:

carrying out ultraviolet treatment on the raw material implant body to obtain an implant body, wherein the surface of the implant body is a hydrophilic surface;

and coating a water-soluble chitosan derivative coating on the implant body or soaking the implant body in an aqueous solution of a water-soluble chitosan derivative to obtain the hydrophilic implant product.

7. The method according to claim 6, wherein the ultraviolet light has a wavelength of 150 to 300nm, preferably 180 to 254 nm.

8. The production method according to claim 6, wherein the ultraviolet irradiation intensity in the ultraviolet treatment is 15 to 1000mW/cm²Preferably 24-200 mW/cm²。

9. The method according to claim 6, wherein the UV irradiation time is 1 to 90min, preferably 60 to 90 min.

10. The method according to claim 6, wherein the temperature of the aqueous solution of the water-soluble chitosan derivative is 10 to 45 ℃ during the soaking.