JP5521189B2 - Film and film manufacturing method - Google Patents

Description

  The present invention relates to a film having temperature responsiveness and a film manufacturing method.

  In the optical field and the electronic field, a so-called porous material having a plurality of fine holes is required. As a material having a fine porous structure that meets such a demand, there is a polymer film having a honeycomb structure, that is, a honeycomb structure in which a large number of fine pores on the μm scale are formed. In the medical field, a film having a fine porous structure is demanded. As a need in the medical field, there is a microporous film used as a regenerative medical material, and for example, it is used as a scaffold for cell culture.

  As a method for producing a porous film, a film having a honeycomb structure of μm scale is formed by casting a solution of a predetermined polymer to form a cast film, and condensing and drying on the cast film. There is. And in this method, many fine holes are formed in the cast film so as to have a honeycomb structure. To make the shape and diameter of the pores as uniform as possible, a hydrophobic polymer (polymer) and an amphiphilic polymer are dissolved in an organic solvent, and a cast film is formed with this solution. Has been proposed (see, for example, Patent Document 1).

  A film having a honeycomb structure that can be used as a super-water-repellent substrate in addition to cell culture and has a through-hole having a pore diameter of 0.01 to 100 μm and made of a water-insoluble polymer has also been proposed (for example, Patent Document 2).

  In many cases, the cultured cells are required to be detached from the scaffold material during culture (hereinafter referred to as a cell culture substrate). Thus, a film composed of a temperature-responsive material that exhibits hydrophilicity at low temperatures and becomes hydrophobic at high temperatures has been proposed (see, for example, Patent Document 3). When cells are cultured on this film, the cultured cells can be easily detached from the film by cooling the temperature of the film in close contact with the cultured cells below a predetermined temperature. A temperature-responsive porous body in which a temperature-responsive material is grafted on the surface of a porous material using such a property of temperature-responsiveness has been proposed (for example, see Patent Document 4).

JP 2007-291367 A JP 2007-319006 A International Publication No. 2002/010349 Pamphlet JP 2005-133080 A

  However, in the porous film of Patent Document 1 and the film of Patent Document 2, although fine pores are formed relatively uniformly, for example, when these are used as a cell culture substrate, cultured cells can be easily treated. It cannot be said that it can be peeled off. Therefore, the use is limited to applications that can be used in close contact with the film, or some chemical treatment or physical treatment is required to peel the cultured cells. When such a treatment is applied, the cultured cells may be changed, the activity of the cultured cells may be lost, or the membrane-shaped cultured cells may be torn off. Therefore, it is desirable to make a film of a material whose surface state or properties change due to other factors without chemical treatment or physical treatment.

  In addition, the temperature-responsive material of Patent Document 3 changes its surface properties due to temperature as a factor. For example, when this is used for cell culture, it is effective in facilitating the detachment of cultured cells. However, since the film obtained from this temperature-responsive material has a smooth surface or a honeycomb structure on the scale of several hundred μm, it cannot be said that there is a wide range of applications. For example, even when used as a cell culture substrate, there is a problem in terms of its culture function. And since the temperature-responsive porous body of patent document 4 has a non-uniform | heterogenous hole, it cannot expect the spread of a use similarly. For example, even when used as a cell culture substrate, there is a problem that the types of cells that can be cultured are extremely limited.

  Then, an object of this invention is to provide the manufacturing method of the film which has a fine structure, and the film which has temperature responsiveness in which a property changes with temperature as a factor.

The film of the present invention has a plurality of holes having the same diameter, or a plurality of protrusions formed on the film surface so that the distance between each is the same, and the hydrophobic portion and the hydrophilic portion It is characterized by being formed of a first polymer having a temperature-responsive portion that reversibly changes at a predetermined temperature between a property and a hydrophobic property .

The first polymer has preferably have a second repeating unit constituting the first repeat unit and a temperature responsive unit constituting the hydrophobic portion. The mass ratio of the temperature responsive part to the first polymer is preferably 1% or more and 95% or less.

  The first repeating unit preferably has a structure represented by the following formula (1), and the second repeating unit preferably has a structure represented by the following formula (2).

In addition, the present invention has a plurality of holes having the same diameter, or a plurality of protrusions formed on the film surface so that the distance between each is the same, and the above formula (1) first polymer that having a second repeating unit represented by the first repeating unit and the formula (2) is configured to include a film, wherein the contained represented in.

The film of the present invention preferably comprises a second Polymer hydrophobic. The mass ratio of the first polymer is preferably in the range of 1% to 90%, and the second polymer is preferably polystyrene or poly (ε-caprolactone).

Furthermore, the method for producing a porous film of the present invention includes a first polymer having a hydrophobic part and a temperature-responsive part that reversibly changes between hydrophilicity and hydrophobicity at a predetermined temperature, and a hydrophobic second polymer. A casting film forming step of casting a solution dissolved in an organic solvent onto a support to form a casting membrane, a dew condensation step for condensing the casting membrane, and the solvent and the dew condensation step. the resulting water droplet is evaporated from the casting film, and is configured as characterized by chromatic and evaporation step to porous film in which a plurality of holes are formed on the film surface. The first polymer preferably has a first repeating unit constituting a hydrophobic part and a second repeating unit constituting a temperature responsive part. The mass ratio of the temperature responsive part to the first polymer is preferably 1% or more and 95% or less. It is preferable to change the response temperature by changing the ratio of the first compound that generates the first repeating unit and the second compound that generates the second repeating unit. The first repeating unit preferably has the structure of the above formula (1), and the second repeating unit preferably has the structure of the above formula (2).

  Further, in the present invention, the porous film in which the plurality of holes are formed so as to have a honeycomb structure is cut at a central portion in the thickness direction, and the film surface side on which the holes are formed is removed. By this, it is comprised including the film manufacturing method made into the film which has a some protrusion on a film surface.

  According to the present invention, the property is remarkably changed due to temperature as a factor, specifically, it has a temperature responsiveness that the property of hydrophilicity and hydrophobicity is reversibly changed, and has a fine uniform structure. Since the film can be easily produced, it can be expected to be used in various applications including a cell culture substrate in which the cultured cells can be easily detached.

It is a top view of the porous film which concerns on this invention. It is sectional drawing which follows the II-II line of FIG. It is sectional drawing which follows the III-III line of FIG. (A) is sectional drawing of the porous film without a partition, (B) is sectional drawing of the porous film with a partition. It is the schematic of the installation which manufactures the porous film of this invention. It is sectional drawing of the film which is another embodiment of this invention. It is explanatory drawing regarding the manufacturing method of the film of FIG. It is sectional drawing of the film which is another embodiment of this invention. It is a NMR chart of the temperature-responsive polymer of this invention. It is a NMR chart of the temperature-responsive polymer of this invention. It is a NMR chart of the temperature-responsive polymer of this invention. It is a NMR chart of the temperature-responsive polymer of this invention. It is explanatory drawing of each coupling | bonding corresponding to the peak of a NMR chart in a temperature-responsive polymer. It is a FT-IR chart of the temperature-responsive polymer of this invention. It is explanatory drawing of each coupling | bonding corresponding to the absorption peak of a FT-IR chart in a temperature-responsive polymer. It is an optical microscope photograph of the porous film of this invention. It is a scanning electron micrograph of the porous film of this invention. It is a scanning electron micrograph of the film which is another embodiment of this invention. It is a graph of the contact angle of the water droplet in the film of this invention. It is an optical microscope photograph of the porous film of this invention. It is a graph showing the relationship between the running speed of a casting belt and opening diameter AP. It is a graph showing the relationship between the light transmittance of the solution of a temperature-responsive polymer, and temperature.

  The film of the present invention contains a temperature-responsive polymer, and this temperature-responsive polymer is a polymer obtained by a polymerization reaction of first and second compounds different from each other.

  One first compound is a substance capable of producing an amphiphilic first homopolymer by polymerization, and this first homopolymer has a hydrophobic part and a hydrophilic part. Shows amphipathic properties. The first homopolymer may have a structure having a main chain as a hydrophobic part and a hydrophilic group as a hydrophilic part, or a hydrophilic part as a hydrophilic part at the end of the main chain as a hydrophobic part. A structure with a group may be used. The hydrophobic part has a structure in which a plurality of first repeating units are continuous, and the first compound has a structure that becomes a first repeating unit by polymerizing with the hydrophilic part.

  The other second compound is a substance capable of producing a temperature-responsive second homopolymer (homopolymer) by polymerization. The temperature responsiveness of the second homopolymer is a property that reversibly changes between hydrophilicity and hydrophobicity at a predetermined temperature, that is, temperature responsiveness relating to hydrophobicity and hydrophilicity. That is, when the temperature is lowered and reaches a predetermined temperature, the second homopolymer changes to hydrophilicity and becomes soluble in water. The second homopolymer has a structure in which a plurality of second repeating units are continuous as a temperature responsive part that exhibits such temperature responsiveness, and the second compound has a structure that becomes a second repeating unit by polymerization. The temperature at which the property changes from hydrophobic to hydrophilic and from hydrophilic to hydrophobic is referred to as “response temperature” in the following description.

  The temperature-responsive polymer is produced by the polymerization reaction of the first compound and the second compound as described above, and has a hydrophobic portion of the first homopolymer and a temperature-responsive portion of the second homopolymer. It is structured. With this structure, hydrophobicity and hydrophilicity can be controlled by temperature control. As a result, this temperature-responsive polymer can produce a temperature-responsive material that reversibly changes between hydrophobic and hydrophilic at a predetermined temperature. Examples of the temperature-responsive material include a cell culture substrate that can control the adhesion force with cells by temperature, and a water-capturing material that selectively captures moisture in the air. And since said temperature-responsive polymer can also be shape-processed by control of a polymerization degree and molecular weight, formation of a shape suitable as a cell culture base material or a water capture | acquisition material material is possible.

  When cell culture is performed on a cell culture substrate using a temperature responsive polymer, that is, on the cell culture substrate made of this temperature responsive polymer or this temperature responsive polymer is mixed with other materials. When cells are cultured on a cell culture substrate, the hydrophobicity is reduced by gradually lowering the temperature of the cell culture substrate in close contact with the cultured cells from the temperature at the time of culturing and lowering the response temperature or lower. The hydrophilicity is increased, and the cultured cells can be peeled from the material without adding chemical treatment or physical treatment to the cultured cells. Therefore, it becomes possible to use cells that have been maintained in a cultured state. When the cell culture substrate that is in close contact with the cultured cells is placed in water or physiological saline having a response temperature or lower, the cultured cells can be easily detached from the material in water or physiological saline.

  When cell culture is performed on a cell culture substrate containing such a temperature-responsive polymer, (1) in the case of a use in which three-dimensionally cultured cells, that is, spheroids are required, without reducing the spheroid thickness. Since it can be peeled off while maintaining the thickness, for example, hepatocyte aggregates excellent in liver function can be obtained. (2) Thin-film cultured cells such as monolayer cultured cells, However, since it can be peeled off without damaging it, there is an effect that cultured cells can be obtained as a membrane.

  In addition, when a film as a water-capturing material containing a temperature-responsive polymer is produced, a mixture of water and a hydrophobic substance is brought into contact with the film from one side, and the temperature of the film is adjusted. When cooled below the response temperature, only water can be retained or passed through the film to separate the water and the hydrophobic material.

  Furthermore, since the temperature-responsive polymer as described above has a hydrophobic part, it has the advantage that it is easily dissolved in an organic solvent to form a film, and further has a temperature-responsive part, so it is kept at a low temperature. Then, there exists an advantage that the film etc. which have a several fine hole can be easily manufactured by formation and holding | maintenance of the water droplets which are mentioned later.

  The mass ratio of the temperature responsive part in the temperature responsive polymer is preferably 1% or more and 95% or less. When this mass ratio is less than 1%, the temperature responsiveness may not be expressed. On the other hand, when it is more than 95%, when it is necessary to dissolve in the hydrophobic organic solvent, Solubility may be too low to dissolve. In addition, this mass ratio is a percentage calculated | required by the type | formula of 100 * x1 / y1, when the formula weight of a temperature-responsive part is x1 and the molecular weight of a temperature-responsive polymer is y1.

  The temperature at which hydrophilicity should be expressed, that is, the temperature at which response is to be made, is controlled by the structure of the second repeating unit.

  The temperature-responsive polymer is preferably a copolymer of a hydrophobic part and a temperature-responsive part in which the hydrophobic part and the temperature-responsive part form a main chain of the polymer. Thus, compared with a copolymer in which one of the hydrophobic part and the temperature-responsive part is a main chain and the other is a side chain, the copolymer is used as a material for culturing cells as a thin film, that is, a film. When it is formed, the strength is large, and the temperature-responsive portion tends to be exposed on the film surface. Such an effect is the same when the copolymer is mixed with a hydrophobic polymer material to form a polymer blend or polymer alloy, and a film is formed from the polymer blend or polymer alloy.

  And it is preferable that the temperature-responsive polymer of this invention is the structure by which the temperature-responsive part was provided to the hydrophilic part at the time of producing | generating a 1st homopolymer. Since the abundance of the hydrophilic portion in the first homopolymer can be predicted, the abundance of the temperature responsive portion when the temperature responsive portion is added can also be predicted. Therefore, in the temperature-responsive polymer to be produced, the amount of the temperature-responsive part can be determined in advance, and this facilitates the detachment of cultured cells at a temperature that changes from hydrophobic to hydrophilic. It becomes possible to control.

  Regarding a temperature-responsive polymer having a structure in which a temperature-responsive part is added to the hydrophilic part when the first homopolymer is produced, the first example is that the first homopolymer is a hydrophobic part. The first compound having a structure having a main chain as a hydrophilic part and a side chain as a hydrophilic part is used as a raw material, and the temperature-responsive polymer obtained in this case is used as a hydrophobic part. It has a main chain and a side chain as a temperature responsive part. The second example is a case where the first homopolymer is used as a raw material such that the first homopolymer has a structure having a hydrophilic group at the terminal, and the temperature-responsive polymer obtained in this case is It is a copolymer in which a hydrophobic part and a temperature-responsive part form a main chain. In both the first and second examples, the temperature-responsive part may be imparted to the hydrophilic group that is the hydrophilic part by an addition reaction, or a part or the whole of the hydrophilic group may be obtained by a substitution reaction. May be substituted. Further, the second example includes a copolymer obtained by an addition polymerization reaction such as a radical polymerization reaction.

  It should be noted that the degree of hydrophilicity of the temperature-responsive polymer when it exhibits hydrophilicity can be changed by changing the mass ratio of the first compound and the second compound. In the present invention, “hydrophobic” refers to a case where the surface has a smooth surface (for example, a film) and the contact angle of the water droplet when the water droplet is placed on the surface is 90 ° or more. “Hydrophilic” refers to the case of less than 90 °. Here, smoothing means that the arithmetic average roughness Ra is less than 10 nm.

  As the first compound, N-dodecylacrylamide (DAm) (molecular weight Mw: 239.4) represented by the following structural formula (3) is preferable. In addition, when this DAm is polymerized, the 1st homopolymer which has a 1st repeating unit represented by following formula (1) is obtained.

  As the second compound, N-isopropylacrylamide (NIPAm) (molecular weight Mw: 113.16) represented by the following structural formula (4) is preferable. In addition, when this NIPAm is polymerized, the 2nd homopolymer which has a 2nd repeating unit represented by following formula (2) is obtained. This second homopolymer is poly N-isopropylacrylamide (PNIPAm), which exhibits hydrophobicity at a temperature higher than about 32 ° C. and hydrophilicity at a temperature lower than about 32 ° C. This is because PNIPAm has an amide and isopropyl group in the side chain, and becomes hydrophobic due to the action of the isopropyl group at a temperature higher than about 32 ° C., compared with a temperature higher than 32 ° C. below about 32 ° C. This is because the affinity of the amide bond with water is very high.

  The temperature-responsive polymer obtained by DAm and NIPAm has a hydrophobic part having a plurality of repeating units of the formula (1) and a temperature-responsive part having a plurality of repeating units of the formula (2). It consists of a first structural unit represented by (5-I) and a second structural unit represented by the following formula (5-II). In the formula (5) representing this temperature-responsive polymer, m represents an integer of 5 to 5000, and n represents an integer of 5 to 5000.

  The temperature-responsive polymer represented by the formula (5) (poly (N-dodecylcyclamide-co-N-isopropylamide), abbreviated as P (DAm-co-NIPAm)) has a number average molecular weight Mn in the range of 4200 to 27322, The weight average molecular weight Mn is preferably in the range of 10,000 to 70,000, and the Mw / Mn is preferably in the range of 2.5 to 4.0.

  In the temperature-responsive polymer represented by the formula (5), the mass ratio of the second structural unit as the temperature-responsive part to the temperature-responsive polymer is 1% or more and 95% or less as described above. preferable. In addition, by changing the ratio of DAm to be copolymerized and NIPAm, the response temperature of the temperature-responsive polymer represented by the formula (5) can be changed in the range of 10 ° C. or more and 50 ° C. or less.

  The temperature-responsive polymer represented by the formula (5) can be obtained by radical polymerization by dissolving DAm and NIPAm together with a radical initiator in a solvent. In this reaction, the molar ratio of DAm to NIPAm is adjusted so that m and n in the formula (5) are in the range of 1 to 5000 in P (DAm-co-NIPAm) to be synthesized. After determining the amount of substances and dissolving each of these components in a solvent, polymerization is carried out at a temperature equal to or higher than the cleavage temperature of the reaction initiator. In addition, the solvent used in this case shall have a boiling point higher than the cleavage temperature of the reaction initiator.

The reaction initiator in radical polymerization of DAm and NIPAm is not particularly limited, but azoisobutyronitrile (2,2′-azobis (2-methylpropionitrile) represented by the formula (6), abbreviated as AIBN, C ₈ H ₁₂ N ₄ , molecular weight Mw: about 160), benzoyl peroxide (BPO) and the like are preferable, and AIBN is particularly preferable. However, the reaction initiator is not limited to these.

  As a solvent in radical polymerization of DAm and NIPAm, benzene, toluene, xylene, chloroform and tetrahydrofuran are preferable, and benzene is particularly preferable. However, the solvent is not limited to these.

  In addition to the 1st compound and the 2nd compound, you may use the 3rd compound different from these 1st and 2nd compounds for the polymer of this invention. That is, the polymer of a 1st compound, a 2nd compound, and a 3rd compound may be sufficient. However, the third compound is used in an amount that does not impair the temperature responsiveness due to the polymerization part of the second repeating unit.

  By using the temperature-responsive polymer as described above, a film capable of easily peeling cultured cells is produced. In the following examples, a film including a temperature-responsive polymer using DAm as the first compound and NIPAm as the second compound, and a method for producing the film will be described.

  1 is a schematic plan view of a first film of the present invention, FIG. 2 is a cross-sectional view taken along line II-II in FIG. 1, and FIG. 3 is a cross-sectional view taken along line III-III in FIG. FIG. 3A shows an embodiment without partition walls, and FIG. 3B shows an embodiment with partition walls. The film 11 is a so-called honeycomb structure porous film having a plurality of holes 12 on one film surface. The holes 12 have a substantially constant shape and size, and are regularly arranged. As shown in FIGS. 2 and 3, the hole 12 may be formed as a depression on one film surface, or may be formed so as to penetrate from one film surface to the other film surface. In some cases (not shown), the present invention includes any aspect.

  In the following description, the opening diameter on the film surface, that is, the diameter of the hole 12 in the plan view when the porous film 11 is viewed as a plane, is the opening diameter AP, the maximum value of the diameter in the hole 12 is the hole diameter D, and the two adjacent holes 12 The distance between the centers is the center-to-center distance L1, the thickness of the porous film 11 is the thickness TA, the thickness of the porous film at the bottom of the hole 12, that is, the minimum thickness of the porous film is the bottom thickness T1, and the depth of the hole 12 is The distance in the plan view of the hole depth L2 and the adjacent holes 12 and the holes 12 is referred to as an inter-hole distance L3, and the thickness of the partition wall 13 between the holes 12 and 12 is denoted by the symbol TP.

  The opening diameter AP is in the range of 10 nm to 100 μm. Thereby, the effect of wettability can be made larger than a so-called flat film having a smooth surface. Moreover, in the porous film 11 in which the holes 12 are formed and the film surface is uneven, the apparent wettability of the surface is more emphasized and expressed as compared with the flat film. Therefore, in the porous film 11, the opening diameter AP is constant within the above range. Thereby, the wettability becomes uniform. When the wettability becomes uniform, the cell culture conditions are made more uniform and the water trapping action is made more uniform than when the wettability is made uniform.

  That the aperture diameter AP is constant means that the aperture diameter variation coefficient is 10% at the maximum, that is, in the range of 0% to 10%. The opening diameter variation coefficient is obtained by the following method. First, in the plan view, n (n is a natural number) adjacent areas of 1 mm × 1 mm are taken in an arbitrary direction. And the average value of opening diameter AP in each area is calculated | required, and let each average value be APS (1), APS (2), ... APS (n-1), APS (n). Then, an average APA of each of these average values is obtained by an expression {APS (1) + APS (2) +... + APS (n−1) + APS (n)} / n. Then, the aperture diameter variation coefficient of the first area having the average value APS (1) is obtained by 100 × | APS (1) −APA | / APA. That is, the aperture diameter variation coefficient is a value obtained for each area of 1 mm × 1 mm, and the aperture diameter variation coefficient of the nth area having the average value APS (n) is 100 × | APS (n) −APA | / APA. Ask for.

  The hole diameter D is constant within a predetermined range. Thereby, the said effect that opening diameter AP is constant increases more.

  The constant pore diameter D means that the coefficient of variation in pore diameter is at most 10%, that is, in the range of 0% to 10%. The hole diameter variation coefficient is obtained by replacing the opening diameter AP with the hole diameter D in the above-described method for obtaining the opening diameter variation coefficient. That is: First, the average value of the hole diameter D in each area divided as described above is obtained, and the average value is defined as DS (1), DS (2),... DS (n−1), DS (n). . Then, the average DSA of these average values is obtained by the formula {DS (1) + DS (2) +... + DS (n−1) + DS (n)} / n. Then, the pore diameter variation coefficient of the first area having the average value DS (1) is obtained by 100 × | DS (1) −DSA | / DSA, and the pore diameter variation coefficient of the nth area having the average value DS (n) is , 100 × | DS (n) −DSA | / DSA.

  When the hole 12 is formed as a depression on one side of the film surface like the porous film 11, the hole diameter D is larger than the opening diameter AP. That is, the thickness TP of the partition wall 13 gradually decreases from the film surface toward the inside. The center-to-center distance L1 may be smaller than the hole diameter D, but may be larger as shown in FIG. In the film 11 of FIG. 3A, the holes 12 and the holes 12 are formed to be continuous with each other. Therefore, a communication path is formed inside the porous film 11 having the honeycomb structure, and there are no partition walls 13. Thus, the porous film 11 having a honeycomb structure having a communication path is an example of the present invention, and the present invention is not limited to this embodiment. For example, as shown in FIG. 3A, a porous film 11 is also included in which the holes are not connected to each other and are independent by the partition wall 13 and there is no communication path inside the film. Is also included.

  The larger the contact angle of the material for culturing cells with water, the easier it is to form spheroids in cell culture. And the contact angle with respect to water tends to increase as the ratio of the opening area to the total area in the plan view of the porous film 11 increases. The ratio of the opening area to the total area is a value obtained by SAP / SU, where SU is the unit area in the plan view, and SAP is the sum of the areas of the hole openings in the unit area SU. Therefore, the contact angle with respect to water can be controlled by controlling the opening diameter AP and the inter-hole distance L3.

  The depth L2, the bottom thickness T1, and the degree of density of the holes 12 are the time from the start of water droplet generation until the water droplet evaporates in the manufacturing method described later, the speed and time for evaporating the solvent, and the solidity of the solution to be cast. It is controlled by the concentration of the fraction.

  The size of the hole 12 determined by the opening diameter AP, the hole diameter D, and the like tends to depend on the thickness TA. That is, when the hole 12 is formed so that the opening diameter AP and the hole diameter D become smaller, the porous film 12 may be made so that the thickness TA becomes smaller. Moreover, when forming the hole 12 large, it is good to make the porous film 12 so that thickness TA may become large. A method for controlling the thickness TA will be described later.

  The porous film 11 is manufactured when the porous film 17, 33, 34 having a thickness L1 of 0.05 μm or more and 100 μm or less, or when the diameter D1 of the hole 31 is 0.05 μm or more and 100 μm or less and the center distance L2 between adjacent holes 31 is L2. This is particularly effective when producing a porous film 17 having a thickness of 0.1 μm or more and 120 μm or less.

  The porous film 11 is made of a mixture of a hydrophobic polymer and a temperature-responsive polymer. However, when the polymerization degree m of the hydrophobic part represented by the formula (5-I) of the temperature-responsive polymer represented by the formula (5) is as large as 100 or more and 5000 or less, the hydrophobic polymer is not used. Only the temperature-responsive polymer may be used as the porous film 11.

  When the mass ratio of the temperature-responsive polymer in the porous film 11 is increased, more temperature-responsive parts are included. Therefore, when the temperature of the porous film 11 is set to be equal to or lower than the response temperature of the temperature-responsive part. It is possible to further improve the ease of cell detachment and to increase the amount of trapped moisture as the moisture trapping material. The mass ratio of the temperature-responsive polymer in the porous film 11 is preferably in the range of 1% to 90%, more preferably in the range of 20% to 80%. When this mass ratio is less than 1%, the function of the temperature-responsive polymer, that is, the temperature responsiveness is not sufficiently developed, and the cultured cells cannot be easily detached, or the moisture trapping action as a moisture trapping material is not achieved. It may not be obtained sufficiently. On the other hand, when the mass ratio is larger than 90%, there is a case where sufficient solubility in the solvent by the hydrophobic portion may not be obtained, and therefore, a solution for producing a film may not be prepared. In addition, said mass ratio is a percentage calculated | required by the type | formula of 100 * x2 / y2, when the mass of a thermoresponsive polymer is x2 and the mass of the porous film 11 is y2.

  The hydrophobic polymer and the temperature-responsive polymer may be in the form of a polymer blend or a polymer alloy, and it does not matter whether or not they are bonded to each other. However, when making a solution for film formation, or before casting the produced solution to form a film, phase separation with a size larger than the opening diameter AP of the hole to be formed does not occur. It is preferable to mix by the method. Therefore, it is preferable that the hydrophobic polymer and the hydrophobic part of the temperature-responsive polymer have affinity. When a large phase separation is observed, a so-called compatibilizing agent for improving the affinity between the hydrophobic polymer and the hydrophobic part of the temperature-responsive polymer may be used.

The method for producing the mixture of the hydrophobic polymer and the temperature-responsive polymer is not particularly limited, and the following methods (1) to (3) can be given as examples.
(1) Put the first compound and the second compound, which are raw materials of the temperature-responsive polymer, in a polymerization solvent, and at any timing before the start of the polymerization reaction, during the polymerization reaction, or after the completion of the polymerization reaction, A hydrophobic polymer is added to the solution and stirred. After stirring, the solvent is removed.
(2) A temperature-responsive polymer is added to a solution in which a hydrophobic polymer is dissolved, and the mixture is stirred and mixed. Thereafter, the solvent is removed.
(3) The hydrophobic polymer and the temperature-responsive polymer are mixed together using a known melt kneader.

  As the hydrophobic polymer constituting the mixture with the temperature-responsive polymer represented by the formula (5), polystyrene represented by the formula (7) is preferable. As the polystyrene, any of atactic, isotactic and syndiotactic can be used. Further, instead of polystyrene, poly (ε-caprolactone), which is a biodegradable polymer, can be used as the hydrophobic polymer. Biodegradable polymers are known to be metabolized in vivo. For this reason, the use of a biodegradable polymer as the hydrophobic polymer greatly increases the expectation that cell release can be performed not only in vitro but also in vivo. Thus, the film of the present invention made using a biodegradable polymer as a hydrophobic polymer is further biodegraded while having temperature responsiveness. For example, it can be used as a biodegradable cell culture substrate. Can be expected.

  FIG. 4 is a schematic view of a porous film manufacturing facility 41. A casting film forming step in which a solution 42 in which a temperature-responsive polymer and a hydrophobic polymer are dissolved is cast on a support to form a casting film 22, and water droplets are formed by condensation on the casting film 22. The condensation process to be formed and the evaporation process for evaporating the solvent and water droplets generated by the condensation from the casting film 22 are both performed in the casting chamber 43. The solvent that has become gas in the casting chamber 43 is recovered by a recovery device (not shown) provided outside the casting chamber. In the present embodiment, the first area 46 for performing the casting process and the dew condensation process, the second area 47 for growing the water droplets and evaporating the solvent, and the third area 48 for evaporating the water droplets are partitioned. Although the integral casting chamber 43 is used, each area may be made independent. However, the first area and the second area are preferably provided as close as possible to each other. By passing through the first to third areas 46 to 48 as described above, the casting film 22 is self-assembled to become the porous film 11 having voids in a predetermined form.

  A casting belt 21 used as a support is stretched around rollers 52 and 53, and a casting die 56 is provided above the casting belt 21. At least one of the rollers 52 and 53 is rotated by a driving device (not shown), whereby the casting belt 21 runs continuously. The temperature of the rollers 52 and 53 is adjusted by the temperature controller 54, whereby the temperature of the casting belt 21 that contacts the rollers 52 and 53 is controlled.

  In the first area 46, when the solution 42 flows out from the casting die 56, the casting film 22 is formed on the casting belt 21. A blower suction unit 61 is provided above the traveling path of the casting film 22. The blower suction unit 61 includes a blower port 61a that flows humidified air in the vicinity of the casting film 22, and an intake port 61b that sucks and exhausts the gas around the cast film 22, and the wind temperature and dew point in the blower system. And a ventilation controller (not shown) for independently controlling the humidity, wind speed, and suction force in the intake system. The air outlet 61a is provided with a filter for maintaining the dustiness, that is, the cleanliness of the humidified air. A plurality of blower units 61 a may be provided side by side in the running direction of the casting belt 21.

Here, when the dew point of the wind from the air outlet 61a is TD, the value obtained by TD-TS is ΔT. At least one of the surface temperature TS and the dew point TD is controlled so that ΔT satisfies the following formula (I). The surface temperature TS of the casting film 22 can be measured by providing non-contact temperature measuring means such as a commercially available infrared thermometer in the vicinity of the casting film 22. If ΔT is less than 3 ° C., water droplets are less likely to be generated, while if ΔT is greater than 30 ° C., water droplets abruptly occur and the size of the water droplets becomes non-uniform, There are cases in which they do not line up on a plane but overlap in three dimensions. In the first area 46, ΔT is preferably changed from a large value to a small value. Thereby, the generation speed of the water droplets and the size of the generated water droplets can be controlled, and the two-dimensional water droplets having a uniform diameter in the surface direction of the casting film 22 can be formed.
3 ° C. ≦ ΔT ≦ 30 ° C. (I)

  In the first area 46, the surface temperature TS of the casting film 22 is controlled by the casting belt 21 and a temperature control plate (not shown) arranged to face the casting belt 21. It may be controlled by either one. Further, the dew point TD is controlled by controlling the condition of the humidified air emitted from the blower suction unit 61.

  In the second area 47, a plurality of air intake / intake units 63 are arranged in order along the traveling path of the casting film 22. Although FIG. 4 illustrates two air intake / intake units, the number is not limited to this. One of the plurality of air intake / intake units 63 on the most upstream side is immediately downstream of the air intake / intake unit 61 in the first area 46. This is because the water droplets formed in the first area 46 are uniformly grown. The more the first area 46 and the second area 47 are separated from each other, that is, the longer the time from the formation of the water droplet to the entry into the second area 47, the more uneven the size of the water droplet when it has grown. End up.

In the second area 47, at least one of the surface temperature TS and the dew point TD is controlled so that ΔT satisfies the following formula (II). The surface temperature TS is mainly controlled by a temperature control plate (not shown). This temperature control plate has basically the same structure as the temperature control plate in the first area, and can change the temperature along the running direction of the casting belt 21. The dew point TD is controlled by controlling the condition of the humidified air from the blower port 63a. In the second area 47, the surface temperature TS of the casting film 22 can be measured by providing a temperature measuring means similar to the above in the vicinity of the casting film 22. By setting the conditions of the second area 47 in this way, it is possible to grow water droplets slowly and promote the arrangement of the water droplets by capillary force, so that uniform water droplets can be formed densely. When ΔT is 0 ° C. or less, the growth of water droplets is not sufficient and does not form a dense state, and the shape and size of the holes and the arrangement of the holes in the porous film may be uneven. On the other hand, when ΔT is larger than 10 ° C., water droplets are locally multilayered, that is, formed in a three-dimensional manner, and the shape and size of the holes and the arrangement of the holes in the porous film may be uneven.
0 ℃ <ΔT ≦ 10 ℃… (II)

  In the second area 47, it is desirable that the surface temperature TS is substantially equal to the dew point temperature TD.

  It is preferable to evaporate as much solvent from the casting film 22 as possible while growing the water droplets. By setting the surface temperature TS and the dew point TD in the second area 47 within the above ranges, the solvent can be sufficiently evaporated and rapid evaporation can be suppressed. Further, it is preferable to selectively evaporate only the solvent without evaporating the water droplets. Therefore, a solvent having a higher evaporation rate than water droplets under the same temperature and pressure is preferable. This makes it easier for water droplets to enter the casting film 22 as the solvent evaporates.

  In the third area 48, a plurality of air intake / intake units 71 to 74 are arranged in order along the traveling path of the casting film 22. In FIG. 4, four air intake / intake units are illustrated, but the number is not limited to this. The air intake / intake unit 71 has the same configuration as the air intake / intake unit 61 described above, but is not limited thereto.

At least one of the surface temperature TS and the dew point TD is controlled so that the surface temperature TS and the dew point TD satisfy the following formula (III). The surface temperature TS is controlled mainly by the temperature control plate 76. Further, the dew point TD control is performed by controlling the condition of the dry air from the air blowing port 63a. In the third area 48, the surface temperature TS of the casting film 22 can be measured by providing a temperature measuring means similar to the above in the vicinity of the casting film 22. By setting the conditions of the third area 48 in this manner, it is possible to produce a porous film 17 having uniform pores by stopping the growth of water droplets and evaporating. When TS ≦ TD, further condensation may occur on the water droplets and the formed porous structure may be destroyed.
TS> TD (III)

  In the third area 48, the main purpose is to evaporate water droplets, but the solvent that could not be evaporated before reaching the third area 48 is also evaporated.

  In the water droplet evaporation process in the third area 48, a reduced pressure drying apparatus may be used instead of the blower suction units 71 to 74. It is easier to adjust the evaporation rates of the solvent and the water droplets by performing the reduced-pressure drying in which the air inside the third area 48 is sucked to reduce the pressure. As a result, the evaporation of the organic solvent and the evaporation of the water droplets can be made better, and the water droplets can be formed better inside the casting film 22, so the size and shape are controlled at the position where the water droplets are present. The formed hole 31 can be formed.

  The film manufacturing equipment 41 further includes a peeling roller 57 that supports the porous film 17 peeled off from the casting belt 21 when the casting film 22 is peeled off from the casting belt 21, and the porous film is sent to the next process. It is done. The next step is, for example, a function providing step for applying various functions to the porous film 17, a winding step for winding the porous film 17 into a roll shape, or the like.

  In the present invention, the air blowing speed of the humidified air from the air blowing / suction units 61, 63, 64 is such that the moving speed of the casting film 22, that is, the relative speed with the running speed of the casting belt 21 is 0.05 m / second or more and 20 m / second. It is preferably in the range of seconds or less. When the relative speed is less than 0.05 m / sec, the casting film 22 may be introduced into the third area 48 (see FIG. 4) before the water droplets are formed in a finely arranged manner. On the other hand, when the relative speed exceeds 20 m / sec, the exposed surface of the casting film 22 may be disturbed or the condensation may not sufficiently proceed.

  In the present embodiment, the case where the long porous film 17 is manufactured by continuously casting the solution 42 is exemplified, but the present invention is not limited to this. For example, the case where the solution 42 is intermittently cast to sequentially produce sheet-like porous films is also included. Moreover, in this embodiment, although the conveyance direction from the 2nd area 47 to the 3rd area 48 and the conveyance direction from the 3rd area 48 to peeling are made into a curve, all the steps from casting to obtaining the porous film 11 are used. The conveyance direction may be a straight line so that the conveyance path is flat.

  It is also possible to form a casting film having a small width by arranging a plurality of casting dies having a length in the width direction shorter than the casting die 56 in the width direction of the support. Furthermore, a plurality of smaller cast films can be formed on the support by intermittently transporting the support in the casting process at shorter time intervals. In addition, a strip-shaped porous film can be produced one after another by dividing the solution outlet of the casting die into a plurality in the width direction and casting the solution 42 intermittently. Furthermore, the manufacturing conditions of the porous film of Unexamined-Japanese-Patent No. 2007-291367 are applicable.

  The porous film 11 can also be manufactured by batch casting. For example, it is the following method. A glass plate or the like is used as a support for casting, and a cast film is formed by placing the solution on the support and spreading it. Then, the support is cooled to cool the casting film, or dew condensation is performed by flowing humidified air around the casting film. A solvent and water droplets generated by dew condensation are evaporated from the cast film to form a porous film 11. When the porous film 11 is formed from a cast film formed on a support such as glass, the dew point, humidity, temperature, etc. are independently controlled for the cast film on the glass plate as shown in FIG. It is preferable to place them sequentially in the first area 46 to the third area 48.

  FIG. 5 is a sectional view of the film of the second embodiment of the present invention. The film 81 has a plurality of protrusions 82 on one side of the film surface. The protrusion 82 has a columnar shape whose diameter increases toward the lower side of the film surface. The heights of the protrusions 82 are the same as each other. The diameter L3 at the end of the protrusion 82 is 1 nm to 5 μm, the center-to-center distance L4 between the adjacent protrusion 82 and the protrusion 82 is 10 nm to 100 μm, and the distance L5 between the protrusion 82 and the protrusion 82 is 5 nm to 100 μm. It is constant.

  The film 81 is manufactured by cutting a honeycomb structure porous film having a plurality of holes having the same diameter on one film surface at the center in the thickness direction and removing the one film surface side. be able to. The central portion is not limited to the center in the thickness direction, and may be between the upper surface and the lower surface. In the porous film having the honeycomb structure, the holes are formed so that the hole diameter D is larger than the opening diameter AP, and the position where the hole diameter D is maximum in the thickness direction, that is, the partition wall 13 is the thinnest. It is preferable to cut at a position. As shown in FIG. 6, the film 81 has a film 84 having a pressure-sensitive adhesive on the surface, to which one of the holes of the porous film 11 is formed, and the film 84 is pulled in the direction indicated by the arrow A. It can be easily manufactured by pulling it off. According to this method, the porous film 11 is easily cut at a position where the hole diameter D is substantially maximum in the thickness direction, that is, at a position where the polymer portion between the holes, that is, the thickness TP of the partition wall 13 is the smallest. The film 81 can be manufactured.

  FIG. 7 shows a third embodiment of the film of the present invention and is a cross-sectional view of the film. The film 91 is provided with a protrusion 92 on one film surface. The protrusion 92 is a needle-like protrusion whose diameter decreases as it approaches the tip. Instead of this shape, only the tip of the protruding portion extending with the same diameter may have a sharp shape. The heights of the protrusions 92 are the same. In the film 91, the distance L5 between the tips of adjacent protrusions 92 is the opening diameter, and the distance L5 is constant in the range of 5 nm to 100 μm. The film 91 has a larger contact angle with water than the film 81 (see FIG. 5) having the same opening diameter AP, and has a greater effect in spheroidizing cells. Thus, since the contact angle with respect to water increases in the order of the porous film 11, the film 81, and the film 91, the hydrophobic strength when exhibiting hydrophobicity increases. Therefore, it can be said that the strength of the hydrophobicity when controlling the hydrophobicity can be controlled by such a shape.

  Similarly to the film 81, the film 91 can be made from the porous film 11 by the same method. That is, the film 81 and the film 91 can be made different by controlling the opening diameter AP, the hole diameter D, and the center distance L1 in the porous film 11. In addition, when the holes of the porous film 11 having a honeycomb structure are communicated to form a communicating path, cutting at the central portion in the thickness direction by the same method as the film 81 manufacturing method, Easy to cut. This is because the position where the communication path is formed has the weakest strength in the thickness direction, and the manufacturing method by stripping using the film 84 as in this embodiment has the properties of such a honeycomb structure. It can be said that this is a simple manufacturing method that takes advantage of this.

  Examples of the present invention will be described below, but the present invention is not limited thereto.

[Experiment 1] to [Experiment 5]
By changing the substance amount ratio (molar ratio) between DAm as the first compound and NIPAm as the second compound as shown in Table 1, five temperature-responsive polymers represented by the formula (5) were synthesized. Before carrying out the polymerization reaction, DAm, NIPAm, and AIBN were each purified by recrystallization. DAm was recrystallized from ethyl acetate, NIPAm was recrystallized from toluene: hexane = 1: 1, and AIBN was recrystallized from methanol.

  DAm and NIPAm are dissolved in benzene as a solvent at each mass shown in Table 1. AIBN as an initiator is then added to this solution. After freezing and degassing the reaction solution, the inside of the reactor containing the reaction solution is purged with nitrogen. Then, the reaction solution is heated to about 65 ° C. to initiate the polymerization reaction. After the polymerization reaction for 6 hours, the temperature of the reaction solution was returned to room temperature (for example, 25 ° C. ± 5 ° C.) and precipitated by reprecipitation. For reprecipitation, the reaction solution was placed in acetonitrile or hot hexane, and a white precipitate was obtained by centrifugation. The resulting white precipitate was dried under reduced pressure at room temperature (for example, 25 ° C. ± 5 ° C.) overnight. A responsive polymer solid was obtained.

  About each obtained temperature-responsive polymer, yield (unit; g), number average molecular weight Mn, weight average molecular weight Mw, Mw / Mn, 1H-NMR measurement, and FT-IR measurement were implemented, respectively. These results are shown in Table 1. However, for Experiment 3, the FT-IR measurement was not performed because the substance amount ratio of the monomer was the same as in Experiment 2.

  In the “NMR measurement result” column of Table 1, a drawing number indicating an absorption spectrum chart by a nuclear magnetic resonance measuring apparatus (manufactured by JEOL Ltd., model: ECX-400) is described.

  In the “FT-IR measurement result” column of Table 1, a drawing number indicating a spectrum chart by a Fourier transform infrared spectrophotometer (manufactured by JASCO Corporation, model: FT-200) is described. This measurement was conducted in the KBr pellet.

  According to the NMR charts of FIGS. 8 to 11, it is confirmed that in each of Experiments 1 to 5, there is no double bond peak of monomers DAm and NIPAm, and each peak showing the structure of formula (5) is observed. It was done. In FIG. 12, reference numerals are given to the respective bonds in the structure of the formula (5).

  According to the IR charts of (a) to (d) of FIG. 13, none of Experiments 1, 2, 4 and 5 has absorption peaks of double bonds of monomers DAm and NIPAm, and the formula (5) It was confirmed that each peak indicating the structure was observed. In FIG. 14, reference numerals are given to the respective structures in the structure of the formula (5).

  A porous film 11 composed of polystyrene and each temperature-responsive polymer obtained in Experiment 1, Experiment 2, Experiment 4, and Experiment 5 of Example 1 was produced. First, 90 parts by mass of polystyrene and 10 parts by mass of the temperature-responsive polymer are dissolved in a solvent so that the mass ratio of the temperature-responsive polymer in the porous film 11 is 10%, and the solid content concentration is 10 mg / mL. Solution 42 was made. The solvent is chloroform. 35 mL to 40 mL of this solution 42 was cast on a glass plate as a casting support to form a casting film 22.

  In place of the film manufacturing equipment 41 of FIG. 4, the first area 46, the second area 47, and the third area 48 are linearly arranged, and the porous film manufacturing equipment includes the first area 46 without the casting die 56. The porous film 11 was manufactured using (not shown). This perforated film manufacturing facility includes a transport means for transporting a glass plate as a support from the first area 46 to the third area 48. The cast film 22 passed through the first area 46, the second area 47, and the third area 48 in order by running the glass plate using this conveying means. The conditions of ΔT in the first to third areas 46 to 48 were 10 ° C. ≦ ΔT ≦ 20 ° C., 0 ° C. <ΔT ≦ 5 ° C., and −30 ° C. ≦ ΔT ≦ −0.5 ° C., respectively. However, ΔT is set to be smaller in the downstream area than in the upstream area. Each porous film 11 is a porous film 11 having partition walls 13 as shown in FIG. An optical micrograph of the surface of each porous film 11 is shown in FIG. 15, and a scanning electron micrograph of the cross section is shown in FIG. The experiment number described in each photograph in FIGS. 15 and 16 is the experiment number in Example 1 in which the temperature-responsive polymer used was produced. The optical microscope is Olympus BX51, and the scanning electron microscope is Hitachi Miniscope TM1000.

  A film 81 having columnar protrusions 82 was produced from the porous film 11 obtained in Example 2 and having the partition walls 13. The used porous film 11 is a porous film 11 using the temperature-responsive polymer obtained in Experiment 1 of Example 1, and is a porous film 11 whose photograph is shown as “Experiment 1” in FIG.

  A scanning electron micrograph of the obtained film 81 is shown in FIG. The microscope used is the aforementioned Hitachi Miniscope TM1000. In the obtained film 81, the diameter L3 at the end of the protrusion 82 is constant at 0.8 μm, the center-to-center distance L4 between the adjacent protrusion 82 and the protrusion 82 is constant at 5.0 μm, and the distance between the protrusion 82 and the protrusion 82 L5 was constant at 4.3 μm.

  Of the porous film 11 obtained in Example 2, each of the three porous films 11 using each temperature-responsive polymer obtained in Experiments 1, 2, and 4 of Example 1 has columnar protrusions 82. Film 81 was made. And about each film 81, the contact angle CAs of the water droplet on the film surface with the protrusion 82 was measured by changing the temperature of the film 81.

  The graph of FIG. 18 is a graph of the contact angle of water drops on the three films 81. The vertical axis represents the contact angle CAs (unit: °), and the horizontal axis represents the temperature of each film 81 (unit: ° C). “Experiment 1” indicated by the square in FIG. 18 means that the temperature-responsive polymer contained in the film 81 is obtained in Experiment 1 of Example 1, and “Experiment 2” indicated by the triangle is “ Means “Experiment 4” in Example 1 and “Experiment 4” indicated by a circle means that it was obtained in Experiment 4 in Example 1.

  As a result of Example 4, as shown in FIG. 18, at a temperature of 30 ° C. or higher, the contact angle CAs is about 150 °, which is a so-called super water-repellent region, but the temperature is around 8 ° C. The contact angle CAs decreased to 90 ° or less when cooled to. This shows that the film of the present invention containing the temperature-responsive polymer changes from high hydrophobicity to hydrophilicity by lowering the temperature.

  The polystyrene in Example 2 was replaced with poly (ε-caprolactone) which is a kind of biodegradable polymer. And the porous film 11 which consists of this poly ((epsilon) -caprolactone) and the temperature-responsive polymer obtained by Experiment 1 of Example 1 was manufactured. Other conditions such as the mass ratio of poly (ε-caprolactone) and the temperature-responsive polymer are the same as in Example 2. As shown in FIG. 3B, the obtained film 11 has partition walls 13 formed thereon.

  An optical micrograph of the surface of the obtained porous film 11 is shown in FIG. The aperture diameter AP of the porous film 11 was 2.5 μm, and the thickness TP of the partition wall 13 in the cross section where the partition wall 13 was the thinnest was 500 nm. From this result, even when poly (ε-caprolactone), which is a biodegradable polymer, is used as the hydrophobic polymer, a multi-solution having temperature responsiveness is formed in the porous film 11 as in the case of using polystyrene. It turns out that it is obtained. Note that the length of the white line in the photograph of FIG. 19 is 5 μm.

  The porous film 11 was manufactured using the porous film manufacturing equipment 41 of FIG. The solution 42 is the same as the solution 42 using polystyrene and the temperature-responsive polymer obtained in Experiment 1 of Example 1 among the solutions used in Example 2. The flow rate of the solution 42 from the casting die 56 was kept constant, and the thickness of the casting film 22 was changed by changing the running speed of the casting belt 21 by changing the rotational speed of the rollers 52 and 53. And the opening diameter AP of the obtained porous film was calculated | required for every running speed of the casting belt 21. FIG. FIG. 20 shows the relationship between the casting belt 21 and the opening diameter AP of the obtained porous film 11.

  In the graph of FIG. 20, the vertical axis represents the opening diameter AP (unit: μm), and the horizontal axis represents the traveling speed (unit: μm / s) of the casting belt 21. From this result, it can be seen that the porous film 11 having a smaller opening diameter AP can be manufactured as the running speed of the casting belt 21 is increased. For example, the porous film 11 having an opening diameter AP of about 2 μm can be produced by changing the traveling speed when the opening diameter AP is 6 μm to a traveling speed twice as large. When the flow rate of the solution 42 is constant, the thickness of the casting film 22 decreases as the traveling speed of the casting belt 21 increases. Therefore, as the thickness of the casting film 22 is reduced, the porous film 11 having a smaller opening diameter AP can be formed. In addition, since the hole diameter D becomes small, so that the opening diameter AP is small, the hole diameter D can also be made small, so that the thickness of the casting film 22 is made small. In place of the solution 42 used in Example 6, a solution 42 using polystyrene and the temperature-responsive polymer obtained in Experiment 2 or Experiment 4 of Example 1 among the solutions used in Example 2 was used. Even if it is used, the opening diameter AP and the traveling speed show the same tendency as the result of the sixth embodiment.

  Moreover, since the film 81 having the protrusions 82 and the films 81 and 91 having the protrusions 92 can be formed from the porous film 11, the film 81 having a smaller distance L5 between the protrusions as the thickness of the casting film 22 is reduced. , 91 can be made. Therefore, by controlling the thickness of the casting film 22, the contact angle of the films 81 and 91 with respect to water can be controlled. Thereby, it turns out that the hydrophilic strength in the temperature which shows hydrophilic property can be adjusted also by control of thickness.

  The temperature responsiveness of the temperature responsive polymer obtained in Experiment 1 of Example 1 was examined. The temperature responsiveness of the polymer can be examined by determining the light transmittance of a solution in which the polymer is dissolved. The lower critical solution temperature LCST (also referred to as lower critical solution temperature, also referred to as lower critical solution temperature) determined in this way is the response temperature of the temperature-responsive polymer. In addition, when a film having a smooth film surface is produced using only this temperature-responsive polymer, the temperature at which hydrophobicity and hydrophilicity change based on the contact angle matches the LCST as described above. .

  The method for obtaining LCST is specifically as follows. First, a temperature-responsive polymer is dissolved in chloroform to form a solution having a concentration of 200 mg / ml. This solution is put into a quartz cell having an optical path length of 1 cm, and this quartz cell is set in a cell holder of an ultraviolet-visible spectrophotometer. The cell holder is provided with a temperature variable jacket, and the temperature of the solution in the quartz cell changes to a predetermined temperature by this jacket. And the transmittance | permeability of the solution in the light whose wavelength (lambda) is 600 nm was each measured at mutually different temperature in the range of 10 to 30 degreeC. The measurement results are shown in FIG. In addition, the used ultraviolet-visible spectrophotometer is JASCO Corporation V-530.

  In the graph of FIG. 21, the vertical axis represents light transmittance (unit:%), and the horizontal axis represents temperature (unit: ° C.). Note that the maximum transmittance is theoretically 100%, but the refractive index of the solution of the temperature-responsive polymer varies depending on the temperature, so a value exceeding 100% may be measured. This may be regarded as an error range. A point indicated by a square is a measured value. When each measured value is connected by a straight line in order from the lowest temperature, it becomes convex downward near 15 ° C. and convex upward near 27 ° C. Assuming that each point is connected by a curve, an inflection point that changes from a downward convex portion to a convex portion is obtained, and the inflection point is about 24 ° C. Therefore, the LCST of this temperature-responsive polymer was 24 ° C., and it was confirmed that the temperature-responsive polymer produced in Experiment 1 of Example 1 had a response temperature of 24 ° C.

DESCRIPTION OF SYMBOLS 11 Porous film 12 Hole 21 Support body 22 Casting film 41 Film manufacturing equipment 42 Solution 46-48 1st-3rd area 81,91 Film 82,92 Protrusion

Claims (14)

The film surface has a plurality of holes having the same diameter, or a plurality of protrusions formed so that the distance between each is the same,
A film formed of a first polymer having a hydrophobic part and a temperature-responsive part that reversibly changes between hydrophilicity and hydrophobicity at a predetermined temperature . Before SL film of claim 1, wherein the first Polymer is characterized and a second repeating unit constituting the first repeating unit and the temperature-responsive portion constituting the hydrophobic portion. 3. The film according to claim 1, wherein a mass ratio of the temperature-responsive portion to the first polymer is 1% or more and 95% or less. The first repeating unit has a structure represented by the following formula (1), and the second repeating unit has a structure represented by the following formula (2). 3. The film according to 3.
The film surface has a plurality of holes having the same diameter, or a plurality of protrusions formed so that the distance between each is the same,
Film characterized to include first Polymer that having a second repeating unit represented by the first repeating unit and the formula represented by the following formula (1) (2).
Film of claims 1 to 5 any one of claims, characterized in that it comprises a second Polymer hydrophobic. The film according to claim 6, wherein a mass ratio of the first polymer is in a range of 1% to 90%. The film according to claim 6 or 7, wherein the second polymer is polystyrene or poly (ε-caprolactone). A solution in which a first polymer having a hydrophobic part and a temperature-responsive part that reversibly changes between hydrophilicity and hydrophobicity at a predetermined temperature and a hydrophobic second polymer are dissolved in an organic solvent. A casting film forming step of casting on a support to form a casting film;
A dew condensation step for dew condensation on the cast film;
Film production method characterized by chromatic and evaporation steps of the solvent and the the water droplets generated by the condensation step is evaporated from the casting film, the porous film having a plurality of holes in the film surface is formed. The film manufacturing method according to claim 9, wherein the first polymer has a first repeating unit constituting the hydrophobic portion and a second repeating unit constituting the temperature responsive portion. 11. The film manufacturing method according to claim 9, wherein a mass ratio of the temperature-responsive portion to the first polymer is 1% or more and 95% or less. The response temperature is changed by changing a ratio of the first compound that generates the first repeating unit and the second compound that generates the second repeating unit. The film manufacturing method of Claim 11 to quote. 13. The film according to claim 10, wherein the first repeating unit has a structure represented by the following formula (1), and the second repeating unit has a structure represented by the following formula (2).
By cutting the porous film in which the plurality of holes are formed so as to have a honeycomb structure at the center in the thickness direction, and removing the film surface side on which the holes are formed,
The film manufacturing method according to claim 9, wherein the film has a plurality of protrusions on the film surface.