JP6432860B2 - Method for producing hybrid gel - Google Patents

Description

  The present invention relates to a hybrid gel and a method for producing a hybrid gel.

  A method for producing a PVA gel (FT gel) in which PVA is physically cross-linked by repeatedly freezing and thawing a polyvinyl alcohol (PVA) solution is conventionally known (Non-patent Document 1). Further, a method for producing a PVA gel (CD gel) in which PVA is physically cross-linked by casting a PVA solution on a support and drying is conventionally known (Non-patent Document 2).

K. Tamura, O. Ike, S. Hitomi, J. Isobe, Y. Shimizu, M. Nambu, A New Hydrogel and Its Medical Application, ASAIO Trans. 32 (1986) 605-609. E. Otsuka and A. Suzuki, A Simple Method to Obtain a Swollen PVA Gel Crosslinked by Hydrogen Bonds, Journal of Applied Polymer Science, 114 (2009) 10-16.

  The PVA gel obtained by the conventional repeated freeze-thaw method is not sufficient in physical properties such as friction characteristics, wear characteristics, swelling characteristics, rigidity, and tensile strength so as to be used as a material that substitutes for biological functions in medical applications. For this reason, the PVA gel which has the more outstanding physical property is calculated | required.

This invention is made | formed in view of the said situation, and makes it a subject to provide the hybrid gel which has the surface whose dynamic friction coefficient (micro | micron | mu) _k is lower than the conventional PVA gel, and its manufacturing method.

The present invention has the following aspects [9] to [21]. The following [1] to [8] are inventions related to the present invention.
[1] The second PVA aqueous solution is cast on the surface of the freeze-thawed gel obtained by freezing and thawing the first PVA aqueous solution, dried, and then swollen with water. A hybrid gel characterized in that cast dry gel is laminated on the surface.
[2] The hybrid gel according to [1], wherein a part of the cast dry gel forms a boundary layer that penetrates into a surface layer of the freeze-thawed gel.
[3] The hybrid gel according to [1] or [2], wherein the freeze-thaw gel is formed by repeating the freezing and thawing a plurality of times.
[4] The weight swelling ratio (W _t / W _d ) between the weight (W _t ) of the hybrid gel in an equilibrium swelling state with respect to water and the weight (W _d ) of the hybrid gel in a dry state, 3-7
The hybrid gel according to any one of [1] to [3] above, wherein
[5] The hybrid according to any one of [1] to [4], wherein a thickness of the cast dry gel of the hybrid gel in an equilibrium swelling state with respect to water is 0.5 mm or more. gel.
[6] The hybrid gel according to any one of [1] to [5], wherein the freeze-thaw gel is formed by repeating the freeze and thaw 2 to 6 times.
[7] In the hybrid gel in an equilibrium swelling state with respect to water, the water permeability of the freeze-thawed gel is 10 times or more larger than the water permeability of the cast dry gel [1] The hybrid gel according to any one of to [6].
[8] The above-mentioned [1] to [1], wherein the freeze-thawed gel is a gel obtained by freezing and thawing the first PVA aqueous solution, followed by drying and further swelling with water. [7] The hybrid gel according to any one of [7].

[9] After the second PVA aqueous solution is cast and dried on the surface of the freeze-thawed gel obtained by freezing and thawing the first PVA aqueous solution, A method for producing a hybrid gel, characterized in that a hybrid gel obtained by laminating cast dry gel on a surface is obtained.
[10] The method for producing a hybrid gel according to [9], wherein the first PVA aqueous solution is repeatedly frozen and thawed to form a freeze-thawed gel.
[11] The method for producing a hybrid gel according to [9] or [10], wherein the cast second PVA aqueous solution is subjected to a treatment for allowing the surface layer portion to penetrate from the surface of the freeze-thawed gel.
[12] The above-mentioned [9] to [9], wherein the freeze-thawed gel is a gel obtained by freezing and thawing the first PVA aqueous solution, followed by drying and further swelling with water. [11] The method for producing a hybrid gel according to any one of [11].
[13] The method according to any one of [9] to [12], wherein the freeze-thawed gel is immersed in water, and a process of eluting uncrosslinked PVA polymer from the frozen-thawed gel is performed. A method for producing a hybrid gel.
[14] The production of the hybrid gel according to any one of [9] to [13], wherein a drying temperature after casting the second aqueous PVA solution is 4 to 12 ° C. Method.
[15] The method according to any one of [9] to [14], wherein the cast second PVA aqueous solution is dried in a state where the freeze-thaw gel is constrained on a support. A method for producing a hybrid gel.
[16] A support having at least a porous surface is used as the support, and after the third PVA aqueous solution is applied to the surface, the freeze-thaw gel is brought into contact with the application surface, and the third The method for producing a hybrid gel according to [15], wherein the freeze-thawed gel is adhered to the surface of the support by drying an aqueous PVA solution.
[17] The above [15] or [16], wherein the support comprises one or more materials selected from the group consisting of metals, metal oxides, glass, ceramics, and calcium-containing materials. A method for producing a hybrid gel.
[18] The method for producing a hybrid gel as described in [16] or [17] above, wherein the average pore diameter of the porous material is 0.1 μm to 600 μm.
[19] The hybrid gel production according to any one of [16] to [18], wherein the second PVA aqueous solution and the third PVA aqueous solution are simultaneously dried. Method.
[20] The hybrid gel according to any one of [9] to [19], wherein the cast second PVA aqueous solution is dried in an atmosphere having a relative humidity of 30 to 90% rh. Production method.
[21] The method for producing a hybrid gel according to [20], wherein the relative humidity of the atmosphere is changed stepwise during the drying period.

The hybrid gel of the present invention has a structure in which a cast dry gel (CD gel) is laminated on a freeze-thaw gel (FT gel). The CD gel constituting the surface of the hybrid gel has a lower dynamic coefficient of friction μ _k compared to a single CD gel. For this reason, the hybrid gel of the present invention can be a promising material as a substitute material for the cartilage of an artificial joint in the medical field.

  In the hybrid gel of the present invention, any functional substance can be contained in the FT gel and the CD gel. For example, a hybrid gel containing chondroitin sulfate and hyaluronic acid that are often present in human joints can be a promising material as the alternative material.

According to the manufacturing method for a hybrid gel of the present invention, as compared with the conventional CD gel, to easily manufacture a hybrid gel having a lower dynamic friction coefficient mu _k. Further, by adjusting the capacities of the first PVA aqueous solution and the second PVA aqueous solution, the dynamic friction coefficient μ _k of the CD gel constituting the outermost surface can be easily adjusted. Furthermore, a hybrid gel having a desired shape can be easily obtained by adjusting the shape of the container when the first PVA aqueous solution and the second PVA aqueous solution are gelled.

Three types of conventional CD gel (CD), hybrid gel (Hybrid) as an example of the present invention, conventional FT gel (FT), and dried FT gel (FTD gel) (FTD) It is a bar graph which compares the dynamic friction coefficient (micro | micron | mu) _k measured by applying a vertical load (0.98N, 2.94N, 5.88N). It is a figure which shows the friction curve of each gel in the case of the vertical load 5.88N of FIG. For the same four gel with 1, it is a bar graph comparing the wear rate e _w measured by applying a same vertical load. It is the figure which plotted the result of CD gel (CD) in FIG. 3A, a hybrid gel (Hybrid), and an FTD gel (FTD). It is a plot figure which shows the elution density | concentration (unit: g / L) of PVA which eluted to the water which immersed each gel in the abrasion test at the time of obtaining the result of FIG. 3A and FIG. 3B. Weight swelling ratios obtained from the weight W _d during the drying and the weight W _t during swelling of the gel _(W t _/ W _d), and is a bar graph representing the 30% compressive stress of each gel. Weight swelling ratios obtained from the weight W _d during the drying and the weight W _t during swelling of the gel _(W t _/ W _d), and is a bar graph representing the 50% compressive stress of each gel. It is a figure which shows the friction curve measured using the spherical probe made from stainless steel about the hybrid gel (Q1) obtained by room temperature drying (25 degreeC), and the hybrid gel (Q2) obtained by low temperature drying (8 degreeC). It is a figure which shows the friction curve measured using the spherical probe made from a ceramic about the hybrid gel (Q1) obtained by room temperature drying (25 degreeC), and the hybrid gel (Q2) obtained by low temperature drying (8 degreeC). It is the photograph which reflected the whole cross section of FT4 gel and CD gel which comprise a hybrid gel (S4). It is the photograph which expanded the boundary part of FT4 gel and CD gel of the hybrid gel (S4) of FIG. It is the photograph which expanded the boundary part of FT4 gel and CD gel of a hybrid gel (S1). A dry thickness of the hybrid gels made by changing the time of infiltration (S1) ~ (S5) ( t f), is a plot showing the thickness (t _g) at the time of swelling. About the hybrid gels (S1) to (S5) produced by changing the time of the permeation treatment, the weight swelling ratio (W _t / W _d ) determined from the weight W _t at the time of swelling and the weight W _d at the time of drying, and the thickness swell ratio calculated from the thickness _{t f} during the drying the thickness _{t g} and _(t g / t _f), is a plot showing. CD gel, FT gel, regardless of the type of hybrid gel, the dynamic friction coefficient mu _k is small gel is a plot showing that smaller the wear rate e _w. It is a plot figure which shows the change of the dynamic friction coefficient (micro | micron | mu) _k when changing the frequency | count of the freeze-thaw cycle of FT gel which comprises a hybrid gel. Is a plot showing the change in the wear rate e _w in the case of changing the number of freeze-thaw cycles of FT gel constituting the hybrid gel. For the hybrid gels (1 _FT ) to (8 _FT ) manufactured by changing the number of freeze-thaw cycles of the FT gel, the weight swelling ratio (W _t / W _d) determined from the weight W _t during swelling and the weight W _d during drying Is a plot diagram showing. It is a plot figure which shows the breaking stress of the hybrid gel (P0)-(P6) produced by changing the relative weight of FT4 gel and CD gel. It is a plot figure which shows the fracture | rupture distortion of the hybrid gel (P0)-(P6) produced by changing the relative weight of FT4 gel and CD gel. It is a plot figure which shows the elastic modulus of the hybrid gel (P0)-(P6) produced by changing the relative weight of FT4 gel and CD gel. It is a graph which shows the friction curve of hybrid gel (Y1)-(Y4) produced by increasing the quantity of CD gel laminated | stacked on a fixed amount of FT4 gel in steps. FIG. 21 is a graph showing superimposed friction curves in the case of a vertical load of 600 gf (5.88 N) in FIG. 20. It is a bar graph which shows each dynamic friction coefficient (micro | micron | mu) _k of the hybrid gel (Y1)-(Y4) at the time of applying three types of perpendicular | vertical load obtained by analyzing the friction curve of FIG. Each dynamic friction coefficient μ _k in the case of the vertical load 600 gf (5.88 N) in FIG. 22 is plotted with a white circle (◯), and each wear rate e _w in the case of the vertical load 600 gf (5.88 N) in FIG. It is the figure plotted by ●). Is a bar graph showing the wear rate e _w of gradually increasing the weight of the CD gel laminated on the constant weight of FT4 gel hybrid gels prepared (Y1) ~ (Y4). It is a schematic diagram which shows the shape of the type | mold of the dumbbell cutter based on JIS-6251-8 standard. It is the graph which compared the dynamic friction coefficient (micro | micron | mu) _k of the hybrid gel (Q2) concerning this invention, and (W1). In the figure, the result of the hybrid gel (Q2) was labeled “no sticking”, and the result of the hybrid gel (W1) was labeled “sticking”. 4 is a graph comparing dynamic friction coefficients μ _k of hybrid gels (Z1) to (Z3) according to the present invention. In the figure, the results of hybrid gels (Z1), (Z2), and (Z3) are “AL60-Hyb-8 ° C 80%”, “AL100-Hyb-8 ° C 80%”, “AL180-Hyb-8 ° C”, respectively. (Refrigerator drying) "label was attached. It is the graph which compared the peeling force when peeling the hybrid gel (Z4)-(Z6) concerning this invention from the alumina plate which is a support body. In the figure, the results of hybrid gels (Z4), (Z1), and (Z2) were labeled “20 μm”, “60 μm”, and “100 μm”, respectively. It is the graph which compared the dynamic friction coefficient (micro | micron | mu) _k (Friction coefficient) of the hybrid gel (J1)-(J3) concerning this invention. In the figure, the results of hybrid gels (J1), (J2), and (J3) are “Hybrid FT4-CD8 ° C 50% rh”, “Hybrid FT4-CD8 ° C60% rh”, “Hybrid FT4-CD8 ° C80”, respectively. Labeled “% rh”. It is the graph which compared the dynamic friction coefficient (micro | micron | mu) _k (Friction coefficient) of the hybrid gel (K1)-(K4) concerning this invention. In the figure, the results of hybrid gels (K1), (K2), (K3), and (K4) are “Hybrid (K1)”, “Hybrid (K2)”, “Hybrid (K3)”, “Hybrid (K4), respectively. ) "Label. It is the photograph which compared the gel surface state of the hybrid gel (K1) concerning this invention before the friction test (a) and after the friction test (b). It is the photograph which compared the gel surface state of the hybrid gel (K3) concerning this invention before the friction test (a) and after the friction test (b). It is the photograph which compared the gel surface state of the hybrid gel (K4) concerning this invention before a friction test (a) and after a friction test (b). It is a cross-sectional schematic diagram of the apparatus structure in the method (2) of a friction test.

  Hereinafter, the present invention will be described based on preferred embodiments.

≪Hybrid gel and manufacturing method thereof≫
The hybrid gel of the first aspect of the present invention is swollen with water after the second PVA aqueous solution is cast and dried on the surface of the freeze-thawed gel obtained by freezing and thawing the first PVA aqueous solution. By this, it is a laminated gel in which a cast dry gel is laminated on the surface of the freeze-thawed gel.

  In the method for producing a hybrid gel according to the second aspect of the present invention, after the second PVA aqueous solution is cast and dried on the surface of the freeze-thawed gel obtained by freezing and thawing the first PVA aqueous solution, This is a method for obtaining a hybrid gel in which a cast dry gel is laminated on the surface of the freeze-thawed gel by swelling with water.

The freeze-thaw gel constituting the hybrid gel is formed by freezing and thawing the first PVA aqueous solution. In the present specification, the freeze-thaw gel may be referred to as “FT gel”.
The cast dry gel constituting the hybrid gel is formed by casting the second aqueous PVA solution on the surface of the freeze-thawed gel (Cast), drying (Dry), and then swelling with water. In the present specification, the cast dry gel may be referred to as “CD gel”.

<PVA aqueous solution>
The first PVA aqueous solution and the second PVA aqueous solution are aqueous solutions in which polyvinyl alcohol (PVA) is dissolved. The first PVA aqueous solution and the second PVA aqueous solution may be the same solution or different solutions. That is, the type and concentration of PVA dissolved in the first PVA aqueous solution may be the same as or different from the type and concentration of PVA dissolved in the second PVA aqueous solution. Below, when only calling it "PVA aqueous solution", it does not distinguish between 1st and 2nd, but points out both PVA aqueous solution.

PVA (polyvinyl alcohol) which is a material of the PVA aqueous solution preferably has a saponification degree of 95% or more and a polymerization degree of 1000 or more.
The upper limit of the saponification degree of PVA is 100%, but from the viewpoint of increasing the solubility of PVA, the saponification degree is preferably less than 100%.
When the degree of polymerization of PVA is 1000 or more, a hybrid gel with high structural strength can be obtained. The upper limit of the degree of polymerization is not particularly limited, but is preferably 3000 or less from the viewpoint of increasing the solubility. Usually, the higher the degree of polymerization of the PVA used, the higher the structural strength of the resulting hybrid gel. PVA having the physical properties exemplified here can be purchased as a commercial product.

Although it does not restrict | limit especially as a density | concentration of the said PVA aqueous solution, Preferably it is 5-25 mass%, More preferably, it is 15-20 mass%.
By setting the PVA aqueous solution concentration within the above range, the density of the physical crosslink formed can be sufficiently increased, and sufficient structural strength can be imparted to the hybrid gel. Moreover, it can prevent that the viscosity of PVA aqueous solution increases and it becomes difficult to inject | pour into a container, and gelatinization of PVA aqueous solution advances during the preservation | save at low temperature.

  The aqueous PVA solution may contain various drugs and functional substances as long as it is not a substance that prevents physical cross-linking of PVA. For example, the functional substance can be supported in the hybrid gel to be formed by previously mixing, dispersing, or dissolving the functional substance in the PVA aqueous solution.

Examples of the functional substance include biological substances existing in human joints such as chondroitin sulfate and hyaluronic acid, inorganic fine particles such as titanium dioxide, organic molecules such as polysaccharides and proteins, and high heat-responsive properties such as N-isopropylacrylamide. A molecule can be exemplified.
The functional substance may be a naturally derived substance or a chemically synthesized substance.
The organic molecule may be a low molecular compound or a high molecular polymer.

  The concentration of the functional substance in the PVA aqueous solution may be, for example, about 10 to 20% by volume, although it depends on the size and physical properties of the functional substance to be used.

<Preparation of freeze-thawing gel (FT gel)>
The FT gel constituting the hybrid gel can be obtained by freezing and thawing the first PVA aqueous solution. For example, it can be obtained by pouring the first PVA aqueous solution into a container such as a petri dish and performing freezing and thawing in a sealed state.

  The shape of the container is not particularly limited, and examples thereof include a plate shape, a cylindrical shape, a rod shape, a box shape, and a spheroid shape. Here, the shape of the container means the shape of the space that fills the PVA aqueous solution. Therefore, the shape of the PVA aqueous solution contained in the container and the hybrid gel to be produced follow the shape of the container.

The temperature of freezing is not particularly limited as long as the temperature capable of freezing the aqueous PVA solution, the freezing point _{T f} of -80 ° C. above the freezing point T _f (15 wt% PVA aqueous solution of about -15.5
Less than -60 ° C and less than the freezing point _Tf , more preferably -30 ° C and less than the freezing point.
The time for the freezing treatment at the freezing temperature is not particularly limited. For example, when a 15% by mass PVA aqueous solution is poured into a container with a thickness of about 1 to 5 mm, it can usually be frozen in about 8 to 24 hours.

The thawing temperature is not particularly limited as long as the frozen PVA aqueous solution can be thawed and does not re-dissolve the physically cross-linked PVA. For example, 0 to 50 ° C is preferable, 4 to 30 ° C is more preferable, and 4 to 15 ° C is still more preferable.
By thawing at a temperature as low as possible within the above range, an FT gel having a high crystallinity, a low swelling ratio, and a strong structural strength can be obtained.
By using FT gel such high strength, the FT dynamic friction coefficient mu _k and wear rate e _w of surface of CD gel to be laminated (the surface of the hybrid gel) on the gel is lower, frictional properties and wear A hybrid gel having excellent properties can be obtained.

  The time for the thawing process at the thawing temperature is not particularly limited. For example, when a 15 mass% PVA aqueous solution is poured into a container with a thickness of about 1 to 5 mm and frozen, it can be thawed usually for about 8 to 24 hours to obtain a wet FT gel.

  From the viewpoint of increasing the structural strength of the FT gel to be formed, the freezing and thawing treatment is preferably repeated a plurality of times. That is, it is preferable that the wet FT gel (FT1 gel) obtained by first freezing and thawing is frozen again and thawed several times.

  In this specification, the FT gel obtained by performing the freeze and thaw cycle once is referred to as FT1 gel, and the FT gel obtained by performing the cycle twice is referred to as FT2 gel. The same applies to the FT gel obtained in the cycle. That is, an FT gel obtained by performing the cycle n times is called an FTn gel.

The FTn gel constituting the hybrid gel is preferably FT2 gel to FT10 gel with n of 2 to 10, more preferably FT2 gel to FT8 gel with n of 2 to 9, and FT2 gel to FT6 gel with n of 2 to 6. Is more preferable.
The number n of cycles of freezing and thawing is not particularly limited, but an FT gel with high structural strength can be obtained by being in the above range. By laminating the CD gel on a FT gel such high strength, the hybrid dynamic friction coefficient mu _k and wear rate e _w a CD gel constituting the outermost surface lower gel, friction characteristics and wear characteristics An excellent hybrid gel can be obtained.

The thickness of the FT gel constituting the hybrid gel can be appropriately set according to the application. For example, a sheet-like hybrid gel can be obtained by using a sheet-like FT gel having a thickness of 0.5 mm to 10 mm.
If the thickness of the sheet-like FT gel is too thin (for example, less than 0.1 mm), the structural strength of the hybrid gel may be weakened. Further, the dynamic friction coefficient μ _k of the surface of the CD gel constituting the hybrid gel and it may be difficult to reduce sufficiently the wear rate e _w.

<Preparation of freeze-thaw dried gel (FTD gel)>
The FT gel constituting the hybrid gel may be a gel obtained by freezing and thawing the first PVA aqueous solution, and then drying and swelling with water. The gel obtained by adding this drying and swelling treatment is called a freeze-thaw dried gel (FTD gel).

  Usually, the structural strength of FTD gel tends to be higher than the structural strength of FT gel. Therefore, by replacing the FT gel constituting the hybrid gel with the FTD gel, the hybrid gel having more excellent friction characteristics and wear characteristics. May be obtained.

  In order to prepare an FTD gel, first, a wet FT gel is prepared by freezing and thawing the first PVA aqueous solution as described above. Subsequently, a dried body obtained by drying the FT gel is obtained, and the dried body is swollen with water, whereby a swollen FTD gel can be obtained.

The FT gel to be dried may be an FT1 gel obtained by performing the freeze and thaw cycle once or an FTn gel obtained by repeating the cycle n times.
The temperature and method for drying the FT gel are not particularly limited, and examples thereof include a method of naturally drying (air drying) until the mass becomes constant under an air atmosphere of about 4 to 40 ° C.

When FTD gel comprises a hybrid gel, the thickness of the FTD gel can be suitably set according to a use. For example, a sheet-like hybrid gel can be obtained by using a sheet-like FTD gel having a thickness of 0.5 mm to 10 mm.
If the thickness of the sheet-like FTD gel is too thin (for example, less than 0.1 mm), the structural strength of the hybrid gel may be weakened. Further, the dynamic friction coefficient μ _k of the surface of the CD gel constituting the hybrid gel and it may be difficult to reduce sufficiently the wear rate e _w.

<In-water immersion treatment of FT gel and FTD gel>
Before laminating the CD gel on the surface of the FT gel or FTD gel constituting the hybrid gel, the uncrosslinked PVA polymer is eluted from the FT gel or FTD gel by immersing the FT gel or FTD gel in water. Is preferred.
By performing this immersion treatment in water, the efficiency with which the second PVA solution permeates the surface of the FT gel or FTD gel can be increased. As a result, it becomes relatively easy for a part of the CD gel to form a boundary layer that penetrates the surface layer of the FT gel or the FTD gel.

As a specific method of the water immersion treatment, for example, FT gel or FTD gel is immersed in ultrapure water of about 20 to 30 ° C., and gently stirred as necessary for about 1 hour to 5 days. The method of immersing is mentioned.
What is necessary is just to set immersion time suitably according to the magnitude | size of a gel. From the viewpoint of sufficiently elution of the uncrosslinked gel, it is usually preferable to immerse the FT gel or FTD gel for a longer time than that required for equilibrium swelling with water.

<Lamination of CD gel>
The second PVA aqueous solution is cast on the surface of the FT gel or FTD gel, dried, and then swollen with water to obtain a hybrid gel in which the CD gel is laminated on the surface of the FT gel or FTD gel.

  After the second PVA aqueous solution is cast on the surface of the FT gel or FTD gel, it is preferable to perform a treatment for allowing the second PVA aqueous solution to penetrate from the surface of the FT gel or FTD gel to the surface layer portion by waiting for a predetermined time. By performing this infiltration treatment, the CD gel can be laminated on the FT gel or the FTD gel while forming a boundary layer in which a part of the CD gel has infiltrated the surface layer of the FT gel or FTD gel.

The time for the infiltration treatment is preferably about 6 hours to 14 days, more preferably about 24 hours to 10 days, and further preferably about 48 hours to 7 days, when it is performed at 8 ° C.
Usually, it is difficult to perform substantial permeation only by allowing it to stand at room temperature for 1 hour. The longer the permeation time, the greater the permeation, so that the boundary layer formed tends to be thicker. However, even if the permeation treatment is continued for more than 14 days, the permeation stagnate and the increase in the thickness of the boundary layer formed tends to reach a peak.

When the temperature of the permeation treatment is higher than room temperature, for example, 40 to 60 ° C., the time required for the permeation treatment may be shortened.
The permeation method may be allowed to stand after casting the second PVA aqueous solution on the FT gel or FTD gel. As described above, since the permeation treatment is performed for a relatively long period of time, it is preferable that the permeation treatment is performed in a sealed state to prevent the cast CD gel from being dried unintentionally.

  After casting the second PVA aqueous solution on the FT gel or the FTD gel, it may be dried immediately or after the permeation treatment, but preferably after the permeation treatment. .

When the permeation treatment is performed and the boundary layer is formed between the FT gel or the FTD gel constituting the hybrid gel and the CD gel, the dynamic friction coefficient μ _k and the wear rate e _w of the surface of the CD gel constituting the hybrid gel are obtained. The friction and wear characteristics are further improved.
Although this mechanism is not clear, the density of PVA in the boundary layer is increased, the amount of PVA microcrystals in the boundary layer is increased, the strength of the boundary layer is increased, etc. It is thought that it contributes to the improvement of the friction characteristics and wear characteristics (that is, the decrease in μ _k and e _w ).

  After the casting or after the infiltration treatment, the FT gel or the FTD gel that has been in a wet state or an equilibrium swelling state when the second PVA aqueous solution is cast, and the second PVA aqueous solution cast thereon are dried. As a result, a dry body is obtained. At this time, it is preferable to dry naturally until the mass becomes constant. If the drying process is stopped in the state of being dried, the physical cross-linking of the CD gel may be insufficient.

The method for drying the second PVA aqueous solution cast on the FT gel or FTD gel is not particularly limited, and for example, it can be dried at about 0 to 30 ° C. in the air or in a reduced pressure atmosphere. The drying temperature is preferably 2 to 20 ° C, more preferably 3 to 16 ° C, and further preferably 4 to 12 ° C. By drying at such a relatively low temperature, the CD gel to be laminated becomes more flexible and can improve the friction and wear properties of its surface (ie, reduce μ _k and e _w ). .

  As the CD gel is formed by drying the cast second PVA aqueous solution, the FT gel or the FTD gel may shrink due to the drying. In order to prevent loss of flatness due to shrinkage and to form a hybrid gel with better frictional properties, the FT gel or FTD gel is restrained or fixed (adhered) to the support in advance before the casting. It is preferable to keep it.

  As a specific restraining method, for example, a method of adhering the peripheral portion of the FT gel or FTD gel to the surface of the support by applying a commercially available adhesive or a third PVA aqueous solution to the surface of the support. It is done. By constraining the peripheral edge, a force is exerted on the FT gel or FTD gel to shrink toward the center of the gel along with the drying, while the peripheral edge of the gel is constrained, which is opposite to the shrinkage. A tensile force acts in the direction of, and a hybrid gel can be formed along the surface shape of the support. When stronger restraint or fixing to the support is required, the adhesive or the third PVA aqueous solution may be applied and adhered to the entire surface of the FT gel or FTD gel. In consideration of medical use, it is preferable to bond using a third PVA aqueous solution in order to avoid elution of chemical substances from commercially available adhesives. The PVA concentration of the third PVA aqueous solution is not particularly limited, and for example, it can be set to the same PVA concentration as the second PVA aqueous solution.

  The FT gel or the adhesive for bonding the FTD gel to the support or the drying of the third PVA aqueous solution may be performed in advance before casting the second PVA aqueous solution on the FT gel or the FTD gel. The drying may be performed simultaneously with the drying of the cast second PVA aqueous solution. By simultaneously carrying out the drying treatment, the production efficiency of the hybrid gel can be improved. Note that it is preferable to apply a small amount of the adhesive or the third PVA aqueous solution used for adhesion so that the adhesion proceeds faster than the formation of the CD gel even when the drying process is simultaneously performed. If the adhesion proceeds faster than the formation of the CD gel, the FT gel or the FTD gel can be sufficiently restrained or fixed to the support during the drying treatment.

  The support preferably has a flat plate shape, and more preferably has a porous surface that restrains the hybrid gel. By using a flat plate-like support, a hybrid gel having excellent frictional properties that is flat and easy to use can be obtained. In addition, by using a porous surface support, the FT gel or FTD gel can be easily restrained on the surface, and the shrinkage of the gel due to drying can be further suppressed. A hybrid gel is obtained.

The average pore diameter of the porous material is not particularly limited, but is preferably 0.1 μm to 600 μm, more preferably 60 μm to 580 μm, and still more preferably 100 μm to 300 μm.
When the FT gel or FTD gel is adhered to the support, the adhesive or the third PVA aqueous solution penetrates the surface in the porous in a short time by being at least the lower limit of the above range. FT gel or FTD gel can be more strongly restrained or fixed to the body.
By being below the upper limit of the above range, the possibility that the excellent friction properties of the CD gel constituting the hybrid gel will be reduced due to the influence of pores on the porous surface. The mechanism by which pores on the porous surface affect the friction characteristics is not clear, but a part of the FT gel or FTD gel falls into the pores on the porous surface, and a fine uneven pattern is formed on the gel surface. One possibility is considered to be a cause.

  The material of the support is not particularly limited, and for example, a support including one or more materials selected from the group consisting of metals, metal oxides, glass, ceramics, and calcium-containing materials is preferable. The metal is not particularly limited, and examples thereof include aluminum, titanium, stainless steel, and gold. The metal oxide is not particularly limited, and examples thereof include alumina (aluminum oxide) and titania (titanium oxide). As the calcium-containing material, for example, hydroxyapatite is a suitable material. Hydroxyapatite is a material suitable for medical use.

  When drying the 2nd PVA aqueous solution cast on FT gel or FTD gel, it is preferable to control temperature and relative humidity. Specifically, when drying at 4 to 25 ° C., the relative humidity is preferably 30 to 90% rh, and when drying at 4 to 15 ° C., the relative humidity is preferably 30 to 80% rh. The relative humidity is more preferably 30 to 70% rh, and the relative humidity is further preferably 30 to 60% rh.

  The temperature and relative humidity when drying the cast second PVA aqueous solution may be uniform (constant) from the start of drying until the end of drying until the mass of the gel becomes constant, gradually or in stages. May be changed. For example, the friction characteristics and wear characteristics can be improved by adopting a drying method in which the temperature is kept constant and the relative humidity is lowered stepwise. Moreover, the friction characteristics and the wear characteristics can be improved by adopting a drying method in which the temperature is raised stepwise and the relative humidity is lowered stepwise. In addition, by controlling the temperature and humidity so that drying progresses slowly in the early stage of the drying process and rapidly proceeds in the later stage of the drying process (drying progresses faster than the initial stage), the friction characteristics and Wear characteristics can be improved. Although the mechanism by which these properties are improved by controlling the temperature and humidity in the drying process is not clear, the minute crystal structure formed in the CD gel that constitutes the hybrid gel contributes to the improvement of the above properties. Can be considered as a cause.

  The drying treatment of the second PVA aqueous solution cast on the FT gel or the FTD gel is preferably dried until the mass of the entire gel becomes constant from the viewpoint of making the physical properties of the gel uniform for each production lot. The moisture content of the dried hybrid gel formed by the drying process varies depending on the temperature and relative humidity of the atmosphere during drying. The moisture content of the hybrid gel after the drying treatment is preferably 5 to 20% by mass with respect to the total mass of the hybrid gel. By performing the drying treatment so that the moisture content is in this range, the microcrystalline structure in the CD gel can be an advantageous structure for improving the friction characteristics and wear characteristics. The water content is determined by measuring the weight Wa of the PVA aqueous solution poured into the petri dish and the film weight Wb when the weight is constant until the weight becomes constant, and the water content = (Wb−Wa × 0.15) ÷ ( It is calculated by the formula of Wa × 0.15) × 100 (%). In this calculation formula, “0.15” is the ratio of the mass of PVA contained in the first PVA aqueous solution.

<Weight and thickness of each gel constituting the hybrid gel>
The weight (W ₂ ) of the second PVA aqueous solution cast on the FT gel or the FTD gel is a relative ratio (W ₁ ) to the weight (W ₁ ) of the first PVA aqueous solution used for the preparation of the FT gel or FTD gel. ₁ / W ₂ ) can be set. Here, since the area of the FT gel or FTD gel and the area of the CD gel to be laminated are basically the same, if the swelling ratio of both phases is constant, the relative ratio of the weights is FT gel or FTD. It is equivalent to the relative ratio between the thickness of the gel and the thickness of the CD gel to be laminated.

Hereinafter, among the PVA aqueous solution used in making the hybrid gel, the thickness of the PVA aqueous solution making the FT gel or FTD gel is referred to as T _1, is cast on the FT gel when stacking the CD gel the thickness of the PVA aqueous solution is referred to as _{T 2,} called the thickness of the PVA aqueous solution to penetrate into the surface layer of the FT gel and _{T 3.}

The relative ratio of the weight (W ₁ / W ₂ ) and the relative ratio of the thickness (T ₁ / T ₂ ) are not particularly limited, but it is preferably adjusted within a range of 0.1 to 10, for example.

When the sum of the weight W ₁ and the weight W ₂ is constant, or when the sum of the thickness T ₁ and the thickness T ₂ is constant, the relative ratio of the weight and the thickness is 1.0 or less. Is preferable, 0.5 or less is more preferable, and 0.2 or less is more preferable. Moreover, the lower limit value of the relative ratio of the weight and the thickness is not particularly limited, but it is usually preferable to set it to 0.1 or more.
By setting the relative ratio to 1.0 or less, the breaking stress, breaking strain and elastic modulus of the hybrid gel can be improved, and the structural strength of the hybrid gel can be increased.

The absolute value of the thickness T ₁ corresponding to the FT gel or FTD gel constituting the hybrid gel can be appropriately set according to the use of the hybrid gel. For example, in medical applications and agricultural applications, it is preferable that the thickness _{T 1} is 0.1mm or more, more preferably 0.5mm or more, more preferably 1.0mm or more. The upper limit of the thickness T ₁ is not particularly limited, as the upper limit value, for example about 50mm can be envisaged.
By appropriately examining in the above range, a hybrid gel having a structural strength suitable for medical use and agricultural use can be obtained.

The absolute value of the thickness T ₂ corresponding to the CD gel constituting the hybrid gel can be appropriately set according to the use of the hybrid gel. For example, in medical applications and agricultural applications, it is preferable that the thickness _{T 2} are at 0.1mm or more, more preferably 0.5mm or more, more preferably 1.0mm or more. The upper limit of the thickness T ₂ are not particularly limited, as the upper limit value, for example about 50mm can be envisaged.
By appropriately discussed above range, it is possible to obtain surface properties suitable for medical applications and agricultural applications, especially dynamic friction coefficient mu _k and / or wear rate e _w low characteristics, a hybrid gel having a.

From the viewpoint of improving the structural strength and the surface characteristics, for example, the thickness T ₁ corresponding to FT gel or FTD gel is set to 1.0 mm to 20 mm, 1.0 mm to 10 mm, or 1.0 mm to 5. set to about 0 mm, and, corresponding to the CD gel to be stacked on the FT gel or FTD gel, the thickness _{T 2, 1.0mm~30mm, 1.5mm~20mm,} or about 2.0mm~10mm Can be set. In addition, the combination shown here is an example and the thickness of the hybrid gel based on this invention is not limited to this.

After setting the weight W ₁ or the thickness T ₁ of the FT gel or FTD gel so as to ensure the structural strength suitable for the hybrid gel applications, securing the weight W ₁ or the thickness T ₁ constant When setting the weight W ₂ or the thickness T ₂ of the CD gel to be laminated, it is preferable that the relationship of weight W ₂ ≧ weight W ₁ or thickness T ₂ ≧ thickness T ₁ is satisfied.
By satisfying the above relationship, it is possible to lower the dynamic friction coefficient mu _k and / or wear rate e _w of surface of CD gel constituting the hybrid gel. Such surface characteristics may be particularly suitable for medical applications.

CD gel corresponds to the thickness of the boundary layer formed in a state of being penetrated into the surface layer portion of the FT gel or FTD gel constituting the hybrid gel, the thickness T ₃ is not particularly limited. According to the above-described infiltration process, usually in the range of 1Myuemu～1000myuemu, preferably capable of adjusting the thickness _{T 3} corresponding to the thickness of the boundary layer in the range of 10 m to 500 m.
From the viewpoint of reducing the dynamic friction coefficient mu _k and / or wear rate e _w of surface of CD gel constituting the hybrid gel, the thickness T ₃ corresponding to the thickness of the boundary layer in the above preferred range, it is preferable as much as possible thick . The thickness T ₂ corresponding to the thickness of the CD gel described above does not include the thickness T ₃ corresponding to the thickness of the boundary layer.

When the thickness of the FT gel or FTD gel constituting the prepared hybrid gel is in an equilibrium swollen state with respect to water, it tends to be thicker than the thickness T ₁ , for example, 1.05 times the thickness T ₁ or more. 1. It may be about 20 times thicker.
The thickness of the CD gel constituting the prepared hybrid gel tends to be thinner than the thickness T ₂ when it is in an equilibrium swelling state with respect to water, for example, 0.90 times to 0.95 times the thickness T _2. May be about twice as thin.
Moreover, each thickness of FT gel, CD gel, and boundary layer which comprises the hybrid gel after preparation can be measured by observing the cross section of a hybrid gel with a phase contrast microscope.

<Weight swelling ratio of hybrid gel>
The weight swelling ratio (W _t / W _d ) between the weight (W _t ) of the hybrid gel in an equilibrium swollen state with respect to water and the weight (W _d ) of the hybrid gel in a dry state is 2 to 10 Are preferable, 3-7 are more preferable, and 4-6 are more preferable. By being in the above range, a hybrid gel having high structural strength can be obtained.

<Water permeability of hybrid gel>
When the hybrid gel described above is in an equilibrium swollen state with respect to water, the water permeability (water permeability) of the CD gel constituting the hybrid gel is determined based on the water permeability of the FT gel or FTD gel constituting the hybrid gel. The ratio can be reduced to about 1/100.
That is, in the hybrid gel in an equilibrium swelling state with respect to water obtained by the above-described production method, the water permeability of the FT gel or FTD gel is 10 times or more than the water permeability of the CD gel, It can be enlarged 100 times or more. According to the production method described above, for example, the ratio of (water permeability of the FT gel or FTD gel) / (water permeability of the CD gel) can be set to about 10 to 100.

For example, by applying a water pressure of 6 kPa on the surface of the FT gel having a thickness of 0.5 mm and the surface of the CD gel having a thickness of 0.5 mm constituting the hybrid gel, the time change of the amount of water that permeates the hybrid gel is changed. The water permeability was calculated from the Hagen-Poiseuille equation. As a result, the water permeability of the CD gel constituting the hybrid gel is about 1 × 10 ^{−15 to} 9 × 10 ⁻¹⁵ (unit: m ⁴ / Ns), and the water permeability of the FT gel is about 1 × 10 ^{−13 to} 9 × 10 ⁻¹³ (unit: m ⁴ / Ns).
Thus, the hybrid gel in which the FT gel has a significantly higher water permeability than the CD gel (the CD gel has a much lower water permeability than the FT gel) is useful in medical and agricultural applications. is there.

<Use of hybrid gel>
Next, an example of a method of using the hybrid gel according to the present invention as an alternative material for artificial cartilage in medical applications will be described.
Examples of the structure of the artificial cartilage include a structure in which the hybrid gel covers the surface of a support member made of calcium phosphate, known ceramics, or the like. At this time, it is preferable to arrange the FT gel or FTD gel of the hybrid gel so as to face the support member, and to arrange the CD gel of the hybrid gel exposed on the surface. The surface of the CD gel thus exposed on the surface can function as the surface of the artificial cartilage. This surface, since it has a conventional low dynamic friction coefficient than PVA gel mu _k and wear rate e _w, in applications where rubbed by the joint can exert particularly excellent friction characteristics and wear characteristics.

  EXAMPLES Next, although an Example demonstrates this invention further in detail, this invention is not limited by these examples.

<Preparation of PVA aqueous solution>
PVA powder (model number: PVA117, manufactured by Kuraray Co., Ltd.) having an average degree of polymerization of 1700 and a degree of saponification of 98.00 to 99.00%, and ultrapure water ion-exchanged with a Milli-Q filter after distillation of ion-exchanged water And were used as materials.
This PVA powder and ultrapure water are put into a screw-cap bottle, prepared to have a PVA concentration of 15.0% by mass, hot water roasted with sufficient stirring (about 2 hours) in warm water of 90 ° C. or higher, The PVA aqueous solution in which the PVA powder was completely dissolved was obtained.
Using this PVA aqueous solution, a sample was prepared by the following method.

<Preparation of comparative freeze-thaw gel (FT gel)>
(1) 30 g of PVA aqueous solution was poured into a petri dish made of polyethylene (PE) having an inner diameter of 85 mm and sealed.
(2) A wet FT gel (thickness: about 2 mm) in which a petri dish was put into a freezer, frozen at −20 ° C. for 8 hours, and gelated by repeating the cycle of thawing at 4 ° C. for 16 hours 1 to 8 times. Got.
Here, the gel obtained in one cycle is called FT1 gel according to the number of cycles of freezing and thawing repeated at the time of FT gel preparation. Similarly, the gel obtained in cycles 2 to 8 is respectively FT2 gel. ~ Called FT8 gel.
(3) In the following comparative test for evaluating physical properties, the FT gel obtained in (2) was immersed in ultrapure water for 3 days, and the uncrosslinked PVA polymer in the FT gel was eluted in water. An equilibrium swollen FT gel (thickness: about 2.5 mm) was used.

<Production of FT gel (FTD gel) with drying treatment for comparison>
(1) 30 g of PVA aqueous solution was poured into a petri dish made of polyethylene (PE) having an inner diameter of 85 mm and sealed.
(2) The petri dish was charged into a freezer, frozen at −20 ° C. for 8 hours, and thawed at 4 ° C. for 16 hours. The cycle was repeated 4 times.
(3) The wet FT4 gel obtained in (2) was dried slowly at 8 ° C. until the mass of the FT4 gel in a wet state became constant, thereby obtaining a dry film. The dried film was immersed in ultrapure water for 3 days to obtain an equilibrium swollen gel (thickness: about 2.5 mm). The gel made of PVA obtained by this production method is hereinafter referred to as FTD gel. When the physical properties of this FTD gel were compared with those of the FT4 gel, the strength increased, the crystallinity increased, and the swelling ratio decreased.
(4) In addition, the outer part (peripheral part) of the wet FT4 gel obtained in (2) is fixed to the plane of the petri dish with an adhesive, and slowly dried at 8 ° C. until the mass of the gel becomes constant. A flat gel having a larger area can be produced by a method of obtaining a dry film.

<Preparation of comparative cast dry gel (CD gel)>
(1) 30 g of PVA aqueous solution was poured into a petri dish made of polyethylene (PE) having an inner diameter of 85 mm.
(2) It was slowly dried until the mass became constant at 8 ° C. to obtain a cast film made of PVA.
(3) The cast film prepared in (2) was immersed in ultrapure water for 24 hours to obtain an equilibrium swollen gel (thickness: 1.2 mm). The CD gel obtained by this production method was used for a comparative test.

<< Comparison of friction and wear characteristics of hybrid gel, CD gel, FTD gel, and FT gel >>

<Preparation of hybrid gel (1)>
A hybrid gel (Q1) in which one layer of cast dry gel was laminated on the FT4 gel was produced as follows. Hereinafter, the cast dry gel is referred to as a CD gel.

A wet FT4 gel was prepared by the same method as the FT gel preparation method described above except that the amount of the PVA aqueous solution used was changed to 15 g.
15 g of the PVA aqueous solution was cast on the surface of this FT4 gel, and dried naturally until the mass became constant at room temperature (about 20 to 30 ° C.) to obtain a dried laminated film. Subsequently, the laminated film is immersed in ultrapure water and swollen, whereby a hybrid gel (Q1) in which one layer of CD gel is laminated on the surface of the FT4 gel (thickness: 2.3 to 2.. 7 mm). In addition, the said PVA aqueous solution used in order to produce a hybrid gel (Q1) is a total of 30g.

<Preparation of hybrid gel (2)>
A hybrid gel (Q2) in which one layer of cast dry gel was laminated on the FT4 gel was prepared as follows. Hereinafter, the cast dry gel may be referred to as a CD gel.

A wet FT4 gel was prepared by the same method as the FT gel preparation method described above except that the amount of the PVA aqueous solution used was changed to 15 g.
15 g of the PVA aqueous solution was cast on the surface of this FT4 gel and dried slowly naturally until the mass became constant at 8 ° C. to obtain a dried laminated film. Subsequently, the laminated film is immersed in ultrapure water and swollen, whereby a hybrid gel (Q2) in which one layer of CD gel is laminated on the surface of the FT4 gel (thickness: 2.3 to 2.. 7 mm). In addition, the said PVA aqueous solution used in order to produce a hybrid gel (Q2) is 30g in total.

《Comparison of friction characteristics》
The CD gel, hybrid gel (Q1, Q2), FTD gel, and FT4 gel obtained above were equilibrated and swollen with ultrapure water, and the friction characteristics in ultrapure water were evaluated. Specifically, a spherical probe (ceramic head, φ = 26 mm) is applied to the surface of each sample by a friction test method (1) described later, and a vertical load of 100 gf (0.98 N), 300 gf (2.94 N). ) Or 600 gf (5.88 N) and repeatedly rubbing, the dynamic friction coefficient μ _k of each sample was measured. In addition, about the hybrid gel (Q1, Q2), the said probe was applied to the outermost CD gel which comprises a hybrid gel (Q1, Q2), and it tested.

As a result, as shown in FIG. 1, the dynamic friction coefficient μ _k of the hybrid gel (Q2) indicated by the label “Hybrid” was the lowest at any vertical load.
Here, in the friction test for obtaining the result shown in FIG. 1, the friction curve of each gel when the vertical load is 600 gf (5.88 N) is shown in FIG. 2, the horizontal axis represents the number of reciprocations of the probe (Reciprocating number The), the vertical axis represents the dynamic friction coefficient mu _k.

From the above results, it is understood that the hybrid gel according to the present invention is more resistant to friction and less worn out than the conventional CD gel, FTD gel, and FT gel.
Moreover, it can be said that the hybrid gel according to the present invention is suitable for uses where a material having a low coefficient of dynamic friction is required, such as a substitute material for cartilage of an artificial joint.

<Comparison of wear characteristics>
The CD gel, hybrid gel (Q1, Q2), FTD gel, and FT4 gel obtained above were equilibrated and swollen with ultrapure water, and their wear characteristics were evaluated. Specifically, a spherical probe (ceramic head, φ = 26 mm) is applied to the surface of each sample by a method described later, and a vertical load of 100 gf (0.98 N), 300 gf (2.94 N), or 600 gf (5 .88N), by rubbing repeatedly while applying, to measure the friction factor _{e w} of each sample. In addition, about the hybrid gel (Q1, Q2), the said probe was applied to the outermost CD gel which comprises a hybrid gel (Q1, Q2), and it tested.

As a result, as shown in FIG. 3A, the friction factor e _w hybrid gels indicated by the label of "Hybrid" (Q2) is the lowest in any of the vertical load.
From this result, it is clear that the hybrid gel according to the present invention is more resistant to friction and less worn out than conventional CD gels, FTD gels, and FT gels.
Moreover, it can be said that the hybrid gel according to the present invention is suitable for uses where a material with a low wear rate is required, such as a substitute material for cartilage of an artificial joint.

Here, the result shown in FIG. 3A is changed to a plot diagram and shown in FIG. 3B. In FIG. 3B, the horizontal axis indicates the vertical load (W _N (N)), and the vertical axis indicates the wear rate e _w (Wear ratio [%]).
Moreover, in the abrasion test when obtaining the results of FIG. 3A and FIG. 3B, the elution amount (unit: g / L) of PVA eluted in the water in which each gel was immersed is shown in FIG. In FIG. 4, the horizontal axis represents the vertical load (Normal load [gf]), and the vertical axis represents the elution amount (Concentration [g / L]).

<< Comparison of swelling ratio and compressive stress of hybrid gel, CD gel, FTD gel, FT gel >>

<Measurement of weight swelling ratio>
The CD gel, hybrid gel (Q2), FT4 gel, and FTD gel were equilibrated and swollen with ultrapure water, respectively, and a 10 mm square test piece was cut out from each gel. The weight W _t of each specimen was measured by an electronic balance. Moreover, the dry body (dry film) which dried each test piece was obtained.
The weight W _d of each dried body was measured by an electronic balance.

For each specimen was weighed, and determined the weight swelling ratios obtained by dividing the weight _{W t} in weight _{W d} a _(W t / W _d). The results are shown by black bar graphs in FIGS.

<< Measurement of 30% compressive stress >>
The CD gel, hybrid gel (Q2), FT4 gel, and FTD gel obtained above were equilibrated and swollen with ultrapure water, and subjected to repeated compression tests by the method described below, and 30% compression stress σ ₃₀ ( Unit: MPa). The result is shown by a white bar graph in FIG.
In addition, it shows that the force required in order to crush the said gel in the thickness direction is so large that compressive stress (sigma) ₃₀ is large.

<< Measurement of 50% compressive stress >>
The CD gel, hybrid gel (Q2), and FT4 gel obtained above were equilibrated and swollen with ultrapure water, and subjected to repeated compression tests by the method described later. 50% compression stress σ ₅₀ (unit: MPa) of each gel ) Was measured. The result is shown by a white bar graph in FIG.
In addition, it shows that the force required in order to crush the said gel in the thickness direction is so large that compressive stress (sigma) ₅₀ is large.

<Comparison of weight swelling ratio and compressive stress>
From the results of FIGS. 5 and 6, the weight swelling ratio (W _t / W _d ) of the hybrid gel (Q2) indicated by the label “Hybrid” was lower than the weight swelling ratio of the conventional CD gel and FT gel. .
Moreover, about 30% compression stress (sigma) ₃₀ and 50% compression stress (sigma) ₅₀ , the hybrid gel (Q2) was higher than the conventional CD gel and FT gel.
From the above measurement results, it is understood that the hybrid gel (Q2) according to the present invention has a stronger shape retention force (rigidity) when subjected to physical compression than the conventional CD gel and FT gel. The Moreover, it can be said that the hybrid gel according to the present invention is suitable for uses where a material having high rigidity is required, such as a substitute material for cartilage of an artificial joint.

<< Physical properties of FTD gel >>
From the results of FIG. 5, it is understood that the FTD gel has high rigidity. However, the dynamic friction coefficient μ _k of the FTD gel labeled “FTD” in FIG. 2 is significantly higher than that of the hybrid gel (Q2) labeled “Hybrid”. Therefore, since the hybrid gel according to the present invention has both high rigidity and a low dynamic friction coefficient μ _{k, it} is more suitable for applications requiring high rigidity and a low dynamic friction coefficient, such as an alternative material for cartilage of an artificial joint, than FTD. It can be said that it is preferable.

<< Comparison of hybrid gel (Q1) and hybrid gel (Q2) >>
The hybrid gels (Q1) and (Q2) obtained above were equilibrated and swollen with ultrapure water, and their friction characteristics were compared. Specifically, two kinds of spherical probes (stainless steel balls, φ = 10 mm; ceramic head, φ = 26 mm) are attached to the outermost CD gel constituting each hybrid gel by the friction test method (1) described later. The sample was subjected to repeated rubbing while applying a vertical load of 600 gf (5.88 N) to measure the dynamic friction coefficient μ _k of each sample. The friction curve obtained by the measurement is shown in FIG. 7A (result using a stainless steel sphere) and FIG. 7B (result using a ceramic bone head). Figure 7A, 7B, the horizontal axis represents the number of reciprocations of the probe (Reciprocating number), the vertical axis represents the dynamic friction coefficient mu _k.

From the results of FIGS. 7A and 7B, the hybrid gel (Q2) subjected to the treatment of drying slowly at 8 ° C. rather than the hybrid gel (Q1) subjected to the treatment of drying at room temperature, regardless of the type of the spherical probe. It is clear that it has a lower dynamic friction coefficient μ _k .
Therefore, it can be said that the hybrid gel (Q2) according to the present invention is more suitable for uses where a material having a low dynamic friction coefficient is required, such as a substitute material for cartilage of an artificial joint.

<< Evaluation of Osmosis Treatment during Hybrid Gel Production >>

<Preparation of hybrid gel (3)>
Hybrid gels (S1) and (S4) in which one layer of cast dry gel was laminated on FT4 gel were prepared as follows. Hereinafter, the cast dry gel may be referred to as a CD gel.

When preparing the hybrid gel (S1), a wet FT4 gel was prepared by the same method as the FT gel preparation method described above except that the amount of the PVA aqueous solution used was changed to 15 g.
15 g of the PVA aqueous solution was cast on the surface of this FT4 gel and dried slowly naturally until the mass became constant at 8 ° C. to obtain a dried laminated film. Subsequently, this laminated film was immersed in ultrapure water and swollen to obtain a hybrid gel (S1) in which one CD gel was laminated on the surface of the FT4 gel.

When preparing the hybrid gel (S4), a wet FT4 gel was prepared by the same method as the FT gel preparation method described above, except that the amount of the PVA aqueous solution used was changed to 15 g.
On the surface of this FT4 gel, 15 g of the PVA aqueous solution was cast, and left to stand for about 5 days (120 hours) in a state of being sealed and preventing drying. A part of the PVA aqueous solution was infiltrated into the surface layer of the FT4 gel by this stationary treatment (penetration treatment). Next, the sealed state was released, and the film was naturally dried at 8 ° C. until the mass became constant, thereby obtaining a dried laminated film. Subsequently, this laminated film was immersed in ultrapure water and swollen to obtain a hybrid gel (S4) in which one CD gel was laminated on the surface of the FT4 gel.

<< Cross-sectional structure of hybrid gels (S1) and (S4) >>
In the cross sections of the hybrid gels (S1) and (S4), the boundary portion between the FT4 gel and the CD gel was observed with a phase contrast microscope.
FIG. 8 shows a photograph showing the entire cross section of the FT4 gel and the CD gel constituting the hybrid gel (S4). The vicinity of the center shows the boundary portion between the FT4 gel and the CD gel.
FIG. 9 shows an enlarged photograph of the boundary portion of the hybrid gel (S4). T = 120h in the photograph indicates that the time for the stationary treatment is 120 hours.
FIG. 10 shows an enlarged photograph of the boundary portion of the hybrid gel (S1). T = 0h in the photograph indicates that the time for the stationary treatment is 0 hour.

  From the cross-sectional photograph, it was confirmed that a boundary layer in which a part of the CD gel penetrated the surface layer of the FT4 gel was formed at the boundary portion of the hybrid gel (S4).

<Preparation of hybrid gel (4)>
One layer of CD on the FT4 gel for the purpose of examining the thickness, weight swelling ratio, and thickness swelling ratio of the hybrid gel when the time of the above-mentioned stationary treatment (penetration treatment) at the time of hybrid gel production is changed. Hybrid gels (S1) to (S5) in which gels were laminated were prepared as follows.

In the preparation of the hybrid gels (S1) and (S4), as described above, the permeation treatment was performed for 0 days (0 hours) or 5 days (120 hours), respectively.
The method for producing the hybrid gel (S2) is the same as the method for producing the hybrid gel (S4), except that the permeation treatment time was changed to 1 day (24 hours).
The method for producing the hybrid gel (S3) is the same as the method for producing the hybrid gel (S4), except that the permeation treatment time was changed to 3 days (72 hours).
The method for producing the hybrid gel (S5) is the same as the method for producing the hybrid gel (S4), except that the permeation treatment time was changed to 15 days (360 hours).

  Using the hybrid gels (S1) to (S5) obtained above, the thickness, weight swelling ratio, and thickness swelling ratio of the hybrid gel when the above-described permeation treatment during hybrid gel production was changed are as follows. I investigated.

<< Thickness of hybrid gel (S1)-(S5) >>
After the permeation treatment, the laminated films (s1) to (s5) were obtained by naturally drying at 8 ° C. until the mass became constant. These thickness t _f of the dried film was measured with calipers. The result is shown by a white circle (◯) plot in FIG.
Thereafter, the thickness t _g of ultrapure water in a hybrid gel obtained by equilibrium swelling of each dry film (S1) ~ (S5) measured by calipers. The result is shown by a black circle (●) plot in FIG.
In FIG. 11, the horizontal axis indicates the number of days t (day) of the permeation treatment, and the vertical axis indicates the thickness (unit: mm).

In the result of FIG. 11, the thickness at the time of swelling of the hybrid gel subjected to the permeation treatment for 1 day to 5 days is thicker than the thickness of the hybrid gel subjected to the permeation treatment for a long period exceeding 5 days. This result is considered to indicate that the PVA aqueous solution gradually permeates from the surface of the FT4 gel into the inside during the infiltration treatment for 1 day to 5 days. Therefore, it is clear that by performing the permeation treatment for 1 to 5 days, the PVA aqueous solution can permeate the surface portion of the FT4 gel and a boundary layer in which a part of the CD gel permeates the surface layer of the FT4 gel can be formed. .
On the other hand, since the thickness of the hybrid gel does not change even after the infiltration treatment for more than 5 days, in this test example, the infiltration of the PVA aqueous solution cast on the FT4 gel peaked out in about 5 days. It is thought that.

<< Weight Swell Ratio and Thickness Swell Ratio of Hybrid Gels (S1) to (S5) >>
Dry laminated films (s1) to (s5) were obtained by the same method as above. These thickness t _f of the dried film was measured with calipers. Thereafter, a 10 mm square test piece was cut out from the hybrid gels (S1) to (S5) which were equilibrium-swelled with ultrapure water. The thickness t _g of each specimen was measured with calipers, and the weight W _t of each specimen was measured by an electronic balance.
Moreover, the dry body (dry film) which dried each test piece at 60 degreeC for 3 days was obtained. The weight W _d of each dried body was measured by an electronic balance.

For each measured hybrid gel, the weight swelling ratio (W _t / W _d ) obtained by dividing the weight W _t by the weight W _d was determined. The result is shown by a white circle (◯) plot in FIG.
About each measured hybrid gel, the weight swelling ratio ( _tg / tf) which divided _| segmented thickness _tg by thickness tf was calculated _| required. The result is shown by a black circle (●) plot in FIG.
In FIG. 12, the horizontal axis indicates the number of days t (day) of the permeation treatment, and the vertical axis indicates the weight swelling ratio or the thickness swelling ratio.

  From the results of FIG. 12, as the penetration time increases, the amount of penetration of the PVA aqueous solution into the FT4 gel increases, and the network density and crystallinity increase at the boundary layer between the CD gel and the FT4 gel. It is believed that the gel thickness has decreased and the hybrid gel strength has increased.

<< Relationship between dynamic friction coefficient and wear rate in CD gel, FT gel, and hybrid gel >>
With respect to the comparative CD gel, the comparative FT4 gel, the hybrid gels (Q1) and (Q2), and the hybrid gels (S1) to (S4), the dynamic friction coefficient μ _k and the wear rate e by the above-described method. _w was measured. The measurement results are shown in FIG. 13, the horizontal axis represents the dynamic friction coefficient mu _k, and the vertical axis shows the wear rate e _w.
About each gel, the measured value at the time of using the said stainless steel spherical probe is shown by the white circle ((circle)) plot in FIG. In addition, the measured values when the ceramic spherical probe is used are shown by black circles (●) in FIG.

In FIG. 13, the correspondence between individual plots and gel types is not shown. Moreover, since the result obtained by measuring several times about the same kind of gel is also included, the number of plots and the number of types of the measured gel do not match.
It can be understood from FIG. 13 that the CD gel, the FT gel, and the hybrid gel have a small wear coefficient e _{w of a} gel having a small dynamic friction coefficient μ _k regardless of the type of the gel.

<< Relationship between the number of freeze-thaw cycles and physical properties of FT gel constituting the hybrid gel >>

<Preparation of hybrid gel (5)>
Hybrid gels (1 _FT ) to (8 _FT ) in which one layer of cast dry gel (CD gel) was laminated on FT1 gel to FT8 gel were prepared as follows.

A wet FT1 gel was prepared by the same method as the FT gel preparation method described above, except that the amount of the PVA aqueous solution used was changed to 15 g. On the surface of this FT1 gel, 15 g of the PVA aqueous solution was cast, and dried naturally at 8 ° C. until the mass became constant, thereby obtaining a dried laminated film. Subsequently, this laminated film was immersed in ultrapure water and swollen to obtain a hybrid gel (1 _FT ) in which one layer of CD gel was laminated on the surface of the FT1 gel.

When preparing a hybrid gel (2 _FT ), a single layer of CD gel is formed on the surface of the FT2 gel by the same method as the method of preparing the hybrid gel (1 _FT ) except that FT2 gel is used instead of FT1 gel. A hybrid gel (2 _FT ) obtained by laminating was obtained.

By using FT3 to FT8 gel instead of FT1 gel in the same manner, hybrid gel (3 _FT ) to hybrid gel (8 _FT ) in which one layer of CD gel is laminated on the surface of FT3 to FT8, respectively Obtained.

In each of the prepared hybrid gels (1 _FT ) to (8 _FT ), the weight of the PVA constituting the FT gel and the weight of the PVA constituting the CD gel were prepared so as to be substantially the same between the hybrid gels. .

_<< Friction characteristics of hybrid gels (1 _FT ) to (8 _FT ) >>
The hybrid gels (1 _FT ) to (8 _FT ) prepared as described above were equilibrated and swollen with ultrapure water, and their friction characteristics were evaluated. Specifically, a spherical probe (ceramic head, φ = 26 mm) is applied to the CD gel constituting the outermost surface of each hybrid gel by a method described later, and a vertical load of 300 gf (2.94 N) or 600 gf (5. The friction coefficient μ _k was measured by repeatedly rubbing while applying 88 N), and the dependence of the FT gel constituting each hybrid gel on the number of freezing and thawing cycles (N _FT ) was examined. The result is shown in FIG.

In FIG. 14, “0 _FT ” is a comparative CD gel obtained by the same method as the preparation of the comparative CD gel and obtained by equilibrium swelling with ultrapure water after drying at 8 ° C. Further, in FIG. 14, the white circle (◯) plot shows the result of the vertical load 300 gf (2.94 N), and the black circle (●) plot shows the result of the vertical load 600 gf (5.88 N).

As shown in FIG. 14, until the number of times to 4 times, the dynamic friction coefficient mu _k decreases as the number increases, the number was almost equal coefficient of dynamic friction mu _k For 4-8 times. From this result, it was found that the frictional properties of the hybrid gels (4 _FT ) to (8 _FT ) are superior to the hybrid gels (1 _FT ) to (3 _FT ).
From the above results, hybrid gels (2 _FT ) to (8 _FT ) are suitable for applications requiring a material having a low dynamic friction coefficient, such as a substitute material for cartilage of an artificial joint, and hybrid gels (3 _FT ) to ( _8FT ) is more suitable, and it can be said that hybrid gels ( _4FT ) to ( _8FT ) are more suitable.

_<< Abrasion characteristics of hybrid gels (1 _FT ) to (8 _FT ) >>
The hybrid gels (1 _FT ) to (8 _FT ) produced as described above were subjected to equilibrium swelling with ultrapure water, and their wear characteristics were evaluated. Specifically, a spherical probe (ceramic head, φ = 26 mm) is applied to the CD gel constituting the outermost surface of each hybrid gel by a method described later, and a vertical load of 300 gf (2.94 N) or 600 gf (5. by rubbing repeatedly while applying 88N), to measure the friction factor e _w, it was investigated the dependence on freezing and the number of thaw cycles FT gel constituting each hybrid gel (N _FT). The result is shown in FIG.

In FIG. 15, “0 _FT ” is a comparative CD gel obtained by the same method as the preparation of the comparative CD gel and obtained by equilibrium swelling with ultrapure water after drying at 8 ° C. Further, in FIG. 15, the white circle (◯) plot shows the result of the vertical load 300 gf (2.94 N), and the black circle (●) plot shows the result of the vertical load 600 gf (5.88 N).

As shown in FIG. 15, until the number of 1 to 4 times, the number of friction ratio e _w decreases with increases, the number was almost the same coefficient of friction e _w For 4-8 times. From these results, it was found that the wear characteristics of the hybrid gels (4 _FT ) to (8 _FT ) were superior to the hybrid gels (1 _FT ) to (3 _FT ).
From the above results, hybrid gels (2 _FT ) to (8 _FT ) are suitable for applications where a material with a low wear rate is required, such as a substitute material for artificial joint cartilage, and hybrid gels (3 _FT ) to ( _8FT ) is more suitable, and it can be said that hybrid gels ( _4FT ) to ( _8FT ) are more suitable.

_<< Weight swelling ratio of hybrid gels (1 _FT ) to (8 _FT ) >>
In order to examine the swelling characteristics of each of the hybrid gels (1 _FT ) to (8 _FT ), the weight swelling ratio was measured. A 10 mm square test piece was cut out from each of the hybrid gels (1 _FT ) to (8 _FT ) equilibrated and swollen with ultrapure water. Wipe off water attached to the surface of the specimen with a paper towel was measured equilibrium swelling weight W _t. Next, a dried product obtained by drying each hybrid gel (1 _FT ) to (8 _FT ) at 60 ° C. for 3 days was obtained, and its weight (dry weight) W _d was measured.
The measured equilibrium swelling weight W _t was divided by the dry weight W _d to calculate the weight swelling ratio (W _t / W _d ).
As a result, as shown in FIG. 16, the number of times increased up to 1-4 times and the weight swelling ratio decreased as the number of times increased, and when the number of times was 4-8 times, the weight swelling ratio was almost equivalent. .

In FIG. 16, “0 _FT ” is a comparative CD gel obtained by equilibrium swelling with ultrapure water after drying at 8 ° C., obtained by the same method as the preparation of the comparative CD gel.

<< Relationship between “FT gel and CD gel thickness ratio” constituting the hybrid gel and physical properties (1) >>

<Preparation of hybrid gel (6)>
Hybrid gels (P0) to (P6) in which one layer of cast dry gel (CD gel) was laminated on FT4 gel were prepared as follows.

The difference between the hybrid gels (P0) to (P6) is that the ratio of the weight of the PVA aqueous solution when preparing the FT4 gel and the weight of the PVA aqueous solution when preparing the CD gel is different. is there. Therefore, the thickness of the FT4 gel increases and the thickness of the CD gel decreases in the order of the hybrid gels (P0) to (P6).
The following table shows the weight of the PVA aqueous solution when preparing the FT4 gel and CD gel of each of the hybrid gels (P0) to (P6).

  As understood from the above table, the hybrid gel (P0) is a CD gel without an FT4 gel. Moreover, a hybrid gel (P6) is FT4 gel which does not have CD gel. Here, for convenience, the CD gel is referred to as a hybrid gel (P0), and the FT4 gel is referred to as a hybrid gel (P6).

  When producing a hybrid gel (P0), that is, a CD gel, a 30 g PVA aqueous solution is poured into a petri dish made of polyethylene (PE) having an inner diameter of 85 mm, and dried until the mass becomes constant at room temperature (about 20 to 30 ° C.). A cast film made of PVA was obtained. This cast film was immersed in ultrapure water for 24 hours to obtain an equilibrium swollen CD gel (thickness: about 1.2 mm) as a hybrid gel (P0).

When preparing the hybrid gels (P1) to (P5), first, each FT gel was obtained by the following method.
(1) A PVA aqueous solution having the weight shown in the above table was poured into a petri dish made of polyethylene (PE) having an inner diameter of 85 mm and sealed.
(2) The petri dish was charged into a freezer, frozen at −20 ° C. for 8 hours, and thawed at 4 ° C. for 16 hours. The cycle was repeated 4 times.
(3) On the surface of the wet FT4 gel obtained in (2), cast the PVA aqueous solution having the weight described in the above table until the mass becomes constant at room temperature (about 20 to 30 ° C.). By drying, a dried laminated film was obtained. Subsequently, the laminated film was immersed in ultrapure water and subjected to equilibrium swelling to obtain hybrid gels (P1) to (P5) in which one layer of CD gel was laminated on the surface of the FT4 gel.

  When preparing a hybrid gel (P6), that is, FT4 gel, pour 30 g of PVA aqueous solution into a polyethylene (PE) petri dish with an inner diameter of 85 mm, seal it, put the petri dish into a freezer and freeze at −20 ° C. for 8 hours. The cycle of thawing at 4 ° C. for 16 hours was repeated four times. Thereafter, the obtained wet FT4 gel was immersed in ultrapure water to obtain an equilibrium swollen FT4 gel (thickness: about 2 mm) as a hybrid gel (P6).

<< Tensile strength of hybrid gels (P0) to (P5) >>
The hybrid gels (P0) to (P5) produced as described above were equilibrated and swollen with ultrapure water, and the tensile strength was evaluated. Specifically, the weight of the PVA aqueous solution used in the preparation of the FT4 gel constituting each hybrid gel was measured by measuring the breaking stress (MPa) and breaking strain by the method described later. The dependence on W was examined.
As a result, as shown in FIG. 17, when the weight W was in the range of 0 to 10 g, the breaking stress decreased as the weight W increased (as the weight ratio of FT4 gel / CD gel increased). When the weight W was in the range of 10 to 25 g, the breaking stress was almost constant even when the weight W increased. On the other hand, as shown in FIG. 18, the breaking strain decreased as the weight W increased (the weight ratio of FT4 gel / CD gel increased). When the weight W exceeded 15 g, the decrease in breaking strain became significant.

<< Elastic modulus of hybrid gels (P0) to (P5) >>
The hybrid gels (P0) to (P5) produced as described above were equilibrated and swollen with ultrapure water, and the elastic modulus was evaluated. The elastic modulus is obtained as the slope of the low strain portion (straight portion) of the stress-strain curve obtained by taking the breaking stress measured as described above on the horizontal axis and the breaking strain on the vertical axis. Based on this elastic modulus, the dependence on the weight W of the PVA aqueous solution used when preparing the FT4 gel constituting each hybrid gel was examined.
As a result, as shown in FIG. 19, the elastic modulus (unit: MPa) decreased as the weight W increased (as the weight ratio of FT4 gel / CD gel increased).

<< "Thickness ratio of FT gel and CD gel" constituting hybrid gel and physical properties (2) >>

<Preparation of hybrid gel (7)>
Hybrid gels (Y1) to (Y4) in which one layer of cast dry gel (CD gel) was laminated on FT4 gel were prepared as follows.

The difference between the hybrid gels (Y1) to (Y4) is that the weight of the PVA aqueous solution is different when the CD gel is laminated on a certain amount (constant thickness) of the FT4 gel.
Therefore, the thickness of the CD gel and the thickness of the hybrid gel increase in the order of the hybrid gel (Y1) to (Y4).
The following table shows the weight of the aqueous PVA solution when producing the FT4 gel and CD gel of each of the hybrid gels (Y1) to (Y4).

When producing the hybrid gels (Y1) to (Y4), first, each FT gel was obtained by the following method.
(1) A PVA aqueous solution having the weight (15 g) described in the above table was poured into a polyethylene (PE) petri dish having an inner diameter of 85 mm and sealed.
(2) The petri dish was charged into a freezer, frozen at −20 ° C. for 8 hours, and thawed at 4 ° C. for 16 hours. The cycle was repeated 4 times.
(3) On the surface of the wet FT4 gel obtained in (2), cast the PVA aqueous solution having the weight described in the above table until the mass becomes constant at room temperature (about 20 to 30 ° C.). By drying, a dried laminated film was obtained. Subsequently, the laminated film was immersed in ultrapure water and subjected to equilibrium swelling to obtain hybrid gels (Y1) to (Y4) in which one layer of CD gel was laminated on the surface of the FT4 gel.

<< Friction Characteristics of Hybrid Gels (Y1) to (Y4) >>
The hybrid gels (Y1) to (Y4) produced as described above were equilibrated and swollen with ultrapure water, and the friction characteristics thereof were evaluated. Specifically, a spherical probe (ceramic head, φ = 26 mm) is applied to a CD gel constituting the outermost surface of each hybrid gel by a friction test method (1) described later, and a vertical load of 100 gf (0.98 N) is applied. ), 300 gf (2.94 N), or 600 gf (5.88 N), while repeatedly rubbing, the dynamic friction coefficient μ _k is measured, and the PVA aqueous solution used in the preparation of the CD gel constituting each hybrid gel The dependence on the weight W _s (that is, the weight W _{s of the} PVA aqueous solution cast on the FT4 gel) was examined.

First, FIGS. 20 and 21 show friction curves showing the relationship between the measured dynamic friction coefficient μ _k and the reciprocating number of the probe.
20 and 21, the friction curve labeled “5 g” is the friction curve of the hybrid gel (Y1), and the friction curves labeled “10 g”, “15 g”, “30 g” are It is a friction curve of hybrid gel (Y2), (Y3), and (Y4), respectively.
In FIG. 20, the friction curves when different vertical loads (100 gf (0.98 N), 300 gf (2.94 N), and 600 gf (5.88 N)) are applied to each hybrid gel are shown in an overlapping manner.
In FIG. 21, the friction curve of each hybrid gel when a vertical load of 600 gf (5.88 N) is applied is superimposed.

Next, as a result of analyzing the above friction curve, as shown in FIG. 22, when the weight W _s is in the range of 5 to 15 g, the weight W _s increases and the weight ratio of the CD gel to the FT4 gel increases. The dynamic friction coefficient μ _k tended to be low. On the other hand, when the weight W _s was in the range of 15 to 30 g, the dynamic friction coefficient μ _k was almost the same even when the weight W _s increased and the weight ratio of the CD gel to the FT4 gel increased.
These results are shown by a white circle (◯) plot in FIG. 23 for a vertical load of 600 gf (5.88 N).

From the above results, it was found that the friction properties of the hybrid gels (Y2), (Y3), and (Y4) are superior to those of (Y1).
Furthermore, hybrid gels (Y2) to (Y4) are preferable and hybrid gels (Y3) to (Y4) are more suitable for applications where a material with a low dynamic friction coefficient is required, such as a substitute material for artificial joint cartilage. It can be said that it is preferable.

<< Abrasion characteristics of hybrid gels (Y1) to (Y4) >>
The hybrid gels (Y1) to (Y4) produced as described above were equilibrated and swollen with ultrapure water, and their wear characteristics were evaluated. Specifically, a spherical probe (ceramic head, φ = 26 mm) is applied to the CD gel constituting the outermost surface of each hybrid gel by a method described later, and vertical loads of 100 gf (0.98 N) and 300 gf (2. 94N), or 600 gf (5.88 N), by rubbing repeatedly while applying, to measure the friction factor _{e w,} the weight _{W s} of the PVA aqueous solution used during the production CD gel constituting each hybrid gel (i.e., The dependence of the PVA aqueous solution cast on the FT4 gel on the weight W _s ) was examined.

Trend As a result, as shown in FIG. 24, in a range weight _{W s} is 5 to 15 g, the higher the weight ratio of CD gel for FT4 gel increases the weight _{W s} is increased, the friction factor _{e w} is low was there. On the other hand, the weight _{W s} is in the range of 15 to 30 g, even increased the weight ratio of CD gel for FT4 gel increases the weight _{W s,} the friction factor _{e w} are almost the same.
These results are shown by black circles (●) in FIG. 23 for a vertical load of 600 gf.

From the above results, it was found that the wear characteristics of the hybrid gels (Y2), (Y3), and (Y4) were superior to (Y1).
Furthermore, hybrid gels (Y2) to (Y4) are preferable and hybrid gels (Y3) to (Y4) are more suitable for applications where a material with a low dynamic friction coefficient is required, such as a substitute material for artificial joint cartilage. It can be said that it is preferable.

<< Formation of CD gel in a state where FT gel is constrained on a support in producing hybrid gel >>

<Preparation of hybrid gel (8)>
A wet FT4 gel was prepared by the same method as the FT gel preparation method described above except that the amount of the PVA aqueous solution used was changed to 15 g.
A 15 wt% PVA aqueous solution was applied to the surface of a polyethylene (PE) petri dish having an inner diameter of 85 mm, and the FT4 gel and the petri dish surface were adhered. This adhesion prevented the FT4 gel from shrinking in the in-plane direction in the subsequent drying step.
Next, 15 g of the PVA aqueous solution was cast on the FT4 gel adhered and fixed on a petri dish, and dried naturally at 8 ° C. until the mass became constant, thereby obtaining a dried laminated film. Subsequently, this laminated film is immersed in ultrapure water and swollen so that a single layer of CD gel is laminated on the surface of the FT4 gel (W1) (thickness: about 2.3 to 2). 0.7 mm). The obtained hybrid gel (W1) was removed from the petri dish used for fixation and used for the following evaluation.
In addition, the said PVA aqueous solution used in order to produce a hybrid gel (W1) is 30g in total.

《Comparison of friction characteristics》
The hybrid gel (W1) and the hybrid gel (Q2) obtained above were each subjected to equilibrium swelling with ultrapure water, and the friction characteristics in ultrapure water were compared. Specifically, by the friction test method (1) described later, a spherical probe is applied to the surface of the CD gel constituting each hybrid gel and repeatedly rubbed while applying a vertical load of 600 gf (5.88 N). The dynamic friction coefficient μ _k of each sample was measured. In this test, an alumina bone head, φ = 26 mm was used.

As a result, as shown in FIG. 26, than the hybrid gel (Q2) as shown by the label "no sticking", towards the dynamic friction coefficient mu _k hybrid gel (W1) shown in the label "with sticking" low And it was stable.
In Figure 26, the horizontal axis below shows the number of reciprocations of the probe (Reciprocating number The), shows a horizontal axis sliding distance of the upper (Sliding Distance (m)), the vertical axis represents the dynamic friction coefficient mu _k.

  From the above results, when the PVA aqueous solution cast on the FT4 gel was dried to form a CD gel, the dynamic friction coefficient was further reduced by performing the above-mentioned drying in a state where the FT4 gel was constrained on the support. It is understood that a hybrid gel is obtained.

<< Humidity control in drying process for forming CD gel during hybrid gel production >>

<Preparation of hybrid gel (9)>
Except that the PVA aqueous solution was poured into a styrene case having an inner size of 59.5 mm × 28.5 mm, and the amount of the PVA aqueous solution used was changed to 5 g, the wet state was obtained by the same method as the FT gel preparation method described above. FT4 gel was prepared.
By applying 3 g of the PVA aqueous solution to the surface of a porous alumina plate having an average pore diameter of 60 μm and allowing to stand for 2 minutes under reduced pressure, a part of the PVA aqueous solution penetrates into the porous surface of the alumina plate. It was.
Next, the FT4 gel is placed on the coated surface, and further 3 g of the PVA aqueous solution is cast on the FT4 gel, and left in a temperature-controlled room with a humidity control function, at 8 ° C. and a relative humidity of 80%. By drying naturally until the mass became constant under an atmosphere of rh, a dried laminated film adhered to the surface of the alumina plate was obtained. Subsequently, the alumina plate is immersed in ultrapure water to swell the laminated film fixed to the surface, thereby swelling the hybrid gel (Z1) (thickness) in which one CD gel is laminated on the surface of the FT4 gel. : About 1.7 to 2.3 mm). The obtained hybrid gel (Z1) was kept fixed on the surface of the alumina plate.

  A single layer of CD gel is formed on the surface of the FT4 gel fixed to the surface of the alumina plate in the same manner as the above-described method for producing the hybrid gel (Z1) except that a porous alumina plate having an average pore diameter of 100 μm is used. A laminated hybrid gel (Z2) (thickness: about 1.7 to 2.3 mm) was produced.

Except for the following (a) and (b), a single layer of CD gel is laminated on the surface of the FT4 gel fixed to the surface of the alumina plate in the same manner as the method for producing the hybrid gel (Z1) described above. The resulting hybrid gel (Z3) (thickness: about 1.7 to 2.3 mm) was produced.
(A) A porous alumina plate having an average pore diameter of 180 μm was used.
(B) The PVA aqueous solution cast on the FT4 gel was naturally dried until the mass became constant in an 8 ° C. refrigerator where humidity control was not performed.

《Comparison of friction characteristics》
The hybrid gels (Z1), (Z2), and (Z3) supported on the alumina plate obtained above were each swelled in equilibrium with ultrapure water, and the friction characteristics in ultrapure water were compared. Specifically, by the friction test method (1) described later, a spherical probe is applied to the surface of the CD gel constituting each hybrid gel and repeatedly rubbed while applying a vertical load of 600 gf (5.88 N). The dynamic friction coefficient μ _k of each sample was measured. In this test, an alumina bone head, φ = 26 mm was used.

As a result, as shown in FIG. 27, the label “AL60-Hyb-8 ° C. 80%” was shown rather than the hybrid gel (Z3) indicated by the label “AL180-Hyb-8 ° C. (refrigeration drying)”. The dynamic friction coefficient μ _k of the hybrid gel (Z1) and the hybrid gel (Z2) indicated by the label “AL100-Hyb-8 ° C. 80%” was lower and more stable.
27, the horizontal axis represents the number of reciprocations of the probe (Reciprocating number The), the vertical axis represents the dynamic friction coefficient mu _k.

  From the above results, when the PVA aqueous solution cast on the FT4 gel is dried to form a CD gel, the above-mentioned drying is performed in an atmosphere in which the temperature and relative humidity are controlled, so that the dynamic friction coefficient is further reduced. It is understood that a gel is obtained.

<Preparation of hybrid gel (10)>
Using a porous alumina plate having an average pore diameter of 20 μm, a single layer of CD gel is laminated on the surface of the FT4 gel fixed to the surface of the alumina plate in the same manner as the above-described method for producing the hybrid gel (Z1). A hybrid gel (Z4) (thickness: about 1.7 to 2.3 mm) was prepared.

<Evaluation of bonding strength to support>
For the above hybrid gels (Z1), (Z2) and (Z4), the bonding force of each hybrid gel to the alumina plate is evaluated by measuring the peeling force when each hybrid gel is peeled from the alumina plate of the support. did.
The peel force was measured (peel test) using a universal testing machine (Instron 5965, manufactured by Instron) at a speed of 1.0 mm / second and a peel angle of 90 °.

As a result, as shown in FIG. 28, in the order of the hybrid gels (Z4), (Z1), and (Z2) indicated by the labels “20 μm”, “60 μm”, and “100 μm”, the peeling force, that is, the alumina plate The bond strength was increasing. Although the results are not shown, the friction characteristics of each of the above hybrid gels were measured. As a result, it was observed that the average pore diameter of the alumina plate was larger, and the greater the binding force of the hybrid gel to the alumina plate, the smaller the dynamic friction coefficient. It was done.
In FIG. 28, the horizontal axis indicates the peel distance (Peel Distance (mm)), and the vertical axis indicates the peel force (Peel Force (N / m)).

<Preparation of hybrid gel (11)>
A wet FT4 gel was prepared by the same method as the FT gel preparation method described above except that the amount of the PVA aqueous solution used was changed to 15 g.
By casting 15 g of the PVA aqueous solution on the FT4 gel, leaving it in a temperature-controlled room with a humidity control function, and naturally drying it until the mass becomes constant in an atmosphere of 8 ° C. and a relative humidity of 50% rh. A dried laminated film was obtained. Subsequently, the laminated film was immersed in ultrapure water and swollen to obtain a hybrid gel (J1) (thickness: about 2 mm) in which one layer of CD gel was laminated on the surface of the FT4 gel. .

<Preparation of hybrid gel (12)>
The hybrid gel (J2) (thickness) was obtained in the same manner as the hybrid gel (J1) except that the drying conditions of the PVA aqueous solution cast on the FT4 gel were changed to an atmosphere of 8 ° C. and a relative humidity of 60% rh. : About 2 mm).

<Preparation of hybrid gel (13)>
The hybrid gel (J3) (thickness) was obtained in the same manner as the hybrid gel (J1) except that the drying conditions of the PVA aqueous solution cast on the FT4 gel were changed to an atmosphere of 8 ° C. and a relative humidity of 80% rh. : About 2 mm).

《Comparison of friction characteristics》
The hybrid gels (J1), (J2), and (J3) obtained as described above, which had no support, were each swelled in equilibrium with ultrapure water, and the friction characteristics in physiological saline were compared. Specifically, according to the friction test method (2) described later, each hybrid gel is placed on an elliptical probe and applied to a flat glass plate in physiological saline, and 300 gf (2.94 N) vertical. The dynamic friction coefficient μ _k of each sample was measured by repeatedly rubbing while applying a load.

As a result, as shown in FIG. 29, the hybrid indicated by each label of “Hybrid FT4-CD8 ° C. 50% rh”, “Hybrid FT4-CD8 ° C. 60% rh”, “Hybrid FT4-CD8 ° C. 80% rh” The dynamic friction coefficient was low and stable in the order of gels (J1), (J2), and (J3).
In FIG. 29, the horizontal axis indicates the sliding distance (Sliding distance [m]) of the probe, and the vertical axis indicates the dynamic friction coefficient μ _k (friction coefficient).

  From the above results, when the PVA aqueous solution cast on the FT4 gel is dried to form a CD gel, the above-mentioned drying is performed in an atmosphere in which the temperature and relative humidity are controlled, so that the dynamic friction coefficient is further reduced. It is understood that a gel is obtained.

<Preparation of hybrid gel (14)>
A wet FT4 gel was prepared by the same method as the FT gel preparation method described above except that the amount of the PVA aqueous solution used was changed to 15 g.
Cast 15 g of the PVA aqueous solution on the FT4 gel, and leave it in a temperature-controlled room with a humidity control function, and set the initial conditions of the drying process to an atmosphere of 15 ° C. and a relative humidity of 80% rh. After drying for 3 days, reduce the relative humidity by 10% rh every day while continuing to dry, and take 5 days to reach an atmosphere of 15 ° C. and a relative humidity of 30% rh as the latter condition of the drying process. Thus, a dried laminated film was obtained by naturally drying until the mass became constant under the latter conditions. Subsequently, the laminated film was immersed in ultrapure water and swollen to obtain a hybrid gel (K1) (thickness: about 2 mm) in which one layer of CD gel was laminated on the surface of the FT4 gel. .

<Preparation of hybrid gel (15)>
The drying conditions of the PVA aqueous solution cast on the FT4 gel were the same as those of the hybrid gel (K1) except that the drying conditions were performed under a constant condition of 15 ° C. and a relative humidity of 30% rh (the latter conditions). By this method, a hybrid gel (K2) (thickness: about 2 mm) was obtained.

<Preparation of hybrid gel (16)>
A wet FT4 gel was prepared by the same method as the FT gel preparation method described above except that the amount of the PVA aqueous solution used was changed to 15 g.
15 g of the PVA aqueous solution is cast on this FT4 gel, left in a temperature-controlled room with a humidity control function, and the initial conditions of the drying process are set to an atmosphere of 8 ° C. and a relative humidity of 50% rh. After drying for 7 days, it was switched to an atmosphere of 20 ° C. and a relative humidity of 40% rh as the latter condition of the drying process, and dried naturally until the mass became constant in the latter condition, thereby obtaining a dried laminated film. . Subsequently, the laminated film was immersed in ultrapure water and swollen to obtain a hybrid gel (K3) (thickness: about 2 mm) in which one layer of CD gel was laminated on the surface of the FT4 gel. .

<Preparation of hybrid gel (17)>
Hybrid gel, except that the drying conditions of the PVA aqueous solution cast on the FT4 gel were dried until the mass was constant under a uniform condition in an atmosphere of 8 ° C. and a relative humidity of 50% rh (the above initial conditions). Hybrid gel (K4) (thickness: about 2 mm) was obtained by the same method as (K3).

《Comparison of friction characteristics》
The hybrid gels (K1), (K2), (K3), and (K4) obtained as described above, which were not supported, were each allowed to equilibrately swell with ultrapure water, and the friction characteristics in physiological saline were compared. Specifically, according to the friction test method (2) described later, each hybrid gel is placed on an elliptical probe and applied to a flat glass plate in physiological saline, and 300 gf (2.94 N) vertical. The dynamic friction coefficient μ _k of each sample was measured by repeatedly rubbing while applying a load.

As a result, as shown in FIG. 30, when the hybrid gels (K1) and (K2) were compared, the hybrid gel (K1) had a lower dynamic friction coefficient and was more stable. Further, when the hybrid gels (K3) and (K4) were compared, the hybrid gel (K3) had a lower dynamic friction coefficient and was more stable.
In FIG. 30, the horizontal axis indicates the sliding distance (Sliding distance [m]) of the probe, and the vertical axis indicates the dynamic friction coefficient μ _k (friction coefficient).

  From the above results, when the PVA aqueous solution cast on the FT4 gel is dried to form a CD gel, the drying rate is relatively slow in the initial stage of the drying process in an atmosphere in which the temperature and relative humidity are controlled. It is understood that a hybrid gel having a further reduced dynamic friction coefficient can be obtained by drying in an atmosphere and drying in an atmosphere where the drying speed is relatively accelerated in the later stage of the drying process.

<Comparison of wear characteristics>
The friction portions of the hybrid gels (K1), (K3), and (K4) after the above-described friction property test was examined with an optical microscope to evaluate the surface wear state.
As a result, as shown in FIGS. 31 (a) and 31 (b), slight cutting marks were observed on the surface of the friction part of the hybrid gel (K1), and the gel structure on the surface was almost damaged. It wasn't. Further, as shown in FIGS. 32 (a) and 32 (b), the surface structure of the wrinkles that existed before the friction test is maintained on the surface of the friction portion of the hybrid gel (K3) even after the friction test. The surface gel structure was hardly damaged. On the other hand, as shown in FIGS. 33 (a) and 33 (b), the surface structure of the wrinkles that existed before the friction test was lost on the surface of the hybrid gel (K4) after the friction test. It was confirmed that a part of the surface gel structure was worn away.

  From the above results, when the PVA aqueous solution cast on the FT4 gel is dried to form a CD gel, the drying rate is relatively slow in the initial stage of the drying process in an atmosphere in which the temperature and relative humidity are controlled. It is understood that a hybrid gel having a further excellent abrasion resistance on the surface of the CD gel can be obtained by drying in an atmosphere and then drying in an atmosphere where the drying speed is relatively accelerated in the latter stage of the drying process.

<< Details of each test method >>

<Method of friction test (1)>
A ball-on-plate repeated friction test was performed using a spherical probe (ceramic head, φ = 26 mm). The test machine used TRIBOGEAR TYPE38 special (made by HEIDON), and performed it in the following procedures.
(1) A strip-shaped (plate-shaped) test piece having a length of 10 mm, a width of 45 mm, and a predetermined thickness was cut out from the test target gel.
(2) After adhering the test piece to the bottom surface in the PE plastic case using Aron Alpha (registered trademark), ultrapure water was poured into the case. At this time, the weight of ultrapure water was 50 times the gel weight.
(3) The PE plastic case was fixed to the stage, and the test was performed by reciprocating while applying a predetermined vertical load while the probe was in contact with the test piece.
(4) The relationship between the number of probe reciprocations and the dynamic friction coefficient μ _k was determined as a friction curve.

Specific test conditions are as follows.
・ Sliding speed: 20 mm / second ・ Reciprocating stroke: 25 mm
・ Number of reciprocations: 2000 times (sliding distance: 100m)
Vertical load: 0.98N (100gf), 2.94N (300gf), 5.88N (600gf)
-Lubricating liquid: Ultrapure water Since the spherical probe is reciprocated at a stroke of 25 mm, 2000 reciprocating movements (Reciprocating Number of Cycle) correspond to 100 m of the sliding distance of the probe. Accordingly, the sliding distance corresponding to the number of reciprocating movements is shown on the upper horizontal axis in FIG. 2, FIG. 7A, FIG. 7B, FIG. 20, FIG.

<Method of friction test (2)>
A test piece of a predetermined shape was cut out from the hybrid gel to be tested, and fixed along a curved surface of an elliptical probe having a cross section of major axis / minor axis = 45 mm / 25 mm via a commercially available adhesive. At this time, the FT gel side of the test piece was adhered, and the CD gel side was exposed (see FIG. 34).
The hybrid gel fixed to the elliptical probe is immersed in physiological saline, and the surface of the CD gel constituting the hybrid gel is brought into contact with a glass plate horizontally disposed in the physiological saline. A ball-on-plate repeated friction test was performed by reciprocating with a vertical load. Through this test, the relationship between the friction distance (Sliding distance (m)) of the probe and the friction coefficient was determined as a friction curve.

Specific test conditions are as follows.
・ Sliding speed: 20 mm / second ・ Reciprocating stroke: 35 mm
・ Slip distance: 140m
・ Vertical load: 2.94N (300gf)
・ Lubricant: Saline

<Method of wear test>
The abrasion test was performed in parallel with the friction test described above.
First, the weight (W _d ) when the gel to be tested was naturally dried until the mass became constant at room temperature was determined. Thereafter, the above-described friction test was performed using the gel to be tested which was equilibrium-swelled with ultrapure water. After finishing the friction test after a predetermined number of reciprocations, the weight (W _e ) of the PVA polymer eluted in the ultrapure water in the plastic case is divided by the weight (W _d ), and the wear rate e _w = W _e / W _d × 100 (%) was calculated.
However, the weight (W _e ) of the PVA polymer eluted by friction (abrasion) is the same as that of the PVA polymer eluted without immersing the test object gel in ultrapure water under the same immersion conditions without conducting the friction test. It is the weight which deducted the weight of as a reference (reference value). Thereby, the weight (W _e ) can be accurately obtained.

The weight (W _e ) of the PVA polymer eluted in the ultrapure water was measured using a total organic carbon analyzer (manufactured by Shimadzu Corporation, model number: TOC-V _CSN ).

<Method of compression test>
Compression tester TA. Using XT plus (manufactured by Stable Micro Systems Ltd.), a compression test was repeatedly performed according to the following procedure.
(1) A square test piece was cut out from each gel balanced and swollen with ultrapure water, and after measuring the lengths of both sides with a caliper, repeated compression tests were performed.
(2a) A flat probe having a larger area than the test piece was pressed, and the test piece was compressed to a strain ε = 30% at a compression speed of 0.01 mm / sec in the air at room temperature. At this time, the test piece was compressed to a strain ε = 30%, released at the same speed, and once returned to zero, the operation of compressing the test piece to the strain ε = 30% was repeated in the same manner. From this result, 30% compression stress σ ₃₀ (unit: MPa) was obtained.
(2b) A flat probe having a larger area than that of the test piece was pressed, and the test piece was compressed to a strain ε = 50% at a compression speed of 0.01 mm / second in the air at room temperature. At this time, the test piece was compressed to a strain ε = 50%, released at the same speed, and after returning to zero, the operation of compressing the test piece to the strain ε = 50% was repeated in the same manner. From this result, 50% compressive stress σ ₅₀ (unit: MPa) was obtained.

<Method of tensile test>
The tensile strength of each sample of the prepared hybrid gel was measured by the following procedure.
(1) Using a dumbbell cutter (see FIG. 25) based on the JIS-6251-8 standard, a test piece cut out from each sample that was balanced and swollen with ultrapure water was prepared.
(2) Two test marks were attached to the test piece using food red, and the distance between the test marks was measured with a caliper.
(3) The width and thickness of the test piece were measured using a micrometer.
(4) A test piece was set on a tensile tester and tested in an equilibrium swelling state where the test piece was immersed in ultrapure water at room temperature while acquiring image data. The tensile tester used was a phosphor bronze leaf spring (length: 145 mm, width: 20 mm, thickness: 2 mm), stepping motor (made by Oriental Motor, model number: EZ-300), strain gauge (made by Kyowa Denki Co., model number: KFG) -2-120-C116L1M2R).
(5) Based on the image data, the change in distance between the gauge points was measured.
(6) From the obtained data, the breaking stress (Breaking Stress) and the breaking strain (Breaking Strain) were obtained.

  The configurations and combinations thereof in the embodiments described above are examples, and the addition, omission, replacement, and other modifications of the configurations can be made without departing from the spirit of the present invention.

Claims (13)

By casting and drying the second PVA aqueous solution on the surface of the freeze-thawed gel obtained by freezing and thawing the first PVA aqueous solution,
A method for producing a hybrid gel, comprising obtaining a hybrid gel in which a cast dry gel is laminated on the surface of the freeze-thaw gel. The method for producing a hybrid gel according to claim 1 , wherein the first PVA aqueous solution is frozen and thawed a plurality of times to form a freeze-thawed gel. Method for producing a hybrid gel of claim 1 or 2, characterized in that the processing of the second aqueous PVA solution described above cast, to penetrate the surface layer portion from the surface of the freeze-thaw gel. As the freeze-thaw gel, after freezing and thawing the first PVA aqueous solution, dried, claims 1 to any one of 3, further characterized by using the obtained gel by swelling with water The method for producing a hybrid gel according to item. The method for producing a hybrid gel according to any one of claims 1 to 4 , wherein the freeze-thawed gel is immersed in water, and a process of eluting uncrosslinked PVA polymer from the frozen-thawed gel is performed. . The method for producing a hybrid gel according to any one of claims 1 to 5 , wherein a drying temperature after casting the second aqueous PVA solution is 4 to 12 ° C. The method for producing a hybrid gel according to any one of claims 1 to 6 , wherein the cast second PVA aqueous solution is dried in a state where the freeze-thawed gel is constrained on a support. A support having at least a porous surface is used as the support. After the third PVA aqueous solution is applied to the surface, the freeze-thawed gel is brought into contact with the application surface to obtain the third PVA aqueous solution. The method for producing a hybrid gel according to claim 7 , wherein the freeze-thawed gel is adhered to the surface of the support by drying. The method for producing a hybrid gel according to claim 7 or 8 , wherein the support includes one or more materials selected from the group consisting of metals, metal oxides, glass, ceramics, and calcium-containing materials. . The method for producing a hybrid gel according to claim 8 or 9 , wherein the porous average pore diameter is 0.1 µm to 600 µm. The method for producing a hybrid gel according to any one of claims 8 to 10 , wherein the drying of the second PVA aqueous solution and the drying of the third PVA aqueous solution are performed simultaneously. The method for producing a hybrid gel according to any one of claims 1 to 11 , wherein the cast second PVA aqueous solution is dried in an atmosphere having a relative humidity of 30 to 90% rh. The method for producing a hybrid gel according to claim 12 , wherein the relative humidity of the atmosphere is changed stepwise during the drying period.