JP7075403B2 - A method for manufacturing a porous hydrogel sheet and a porous hydrogel sheet manufactured by the manufacturing method. - Google Patents

Description

The present invention relates to a method for producing a porous hydrogel sheet and a porous hydrogel sheet produced by the method, and more particularly, the liquid absorption is improved by including a step of pre-freezing and freeze-drying the hydrogel sheet. The present invention relates to a method for producing a porous hydrogel sheet and a porous hydrogel sheet produced by the method.

Hydrogel is a network of hydrophilic polymer chains that use water as a dispersion medium. The hydrogel swells insoluble in water and can contain a large amount of water in its structure, exhibiting flexibility very similar to natural tissue.

Due to its unique hydrophilicity and flexibility, the hydrogels are used in pharmaceutical fields such as tissue engineering, cell culture, sustained-release drug delivery system, biosensors, soft. It is used for lenses, medical electrodes, etc., and its application fields are also diversified, such as absorbents for sanitary products and transmission media for beauty agents.

As a conventional technique using such a hydrogel, Patent Document 1 (Korean Patent Publication No. 10-2014-0116325) states (a) a liquid natural polymer substance and a plasticizer, an electrolyte, and a functional cosmetic. Steps of mixing ingredients, preservatives and water in specific proportions; (b) heating the composition to a temperature of 70-90 ° C. for the mixture of steps (a) above to create a gelled hydrogel composition. A method for producing a hydrogel composition is described, which comprises a step of making a substance; (c) a step of putting the heated composition into a molding die to produce a gel-like hydrogel molded product. At this time, the hydrogel composition is one selected from 0.1 to 3% by weight of Cassia Gum, which is a natural polymer substance, Carrageenan Gum, or Xanthan Gum, or a mixture thereof. 0.1 to 2% by weight, polyhydric alcohols 5 to 30% by weight as plasticizer, 0.5 to 2% by weight of polymer, 0.1 to 10% by weight of functional cosmetic ingredient that imparts skin beauty function, preservative According to the above-mentioned Patent Document 1, a hydrogel film having an excellent tear strength can be provided, which contains 0.001 to 0.5% by weight and the balance of water.

However, in the case of the hydrogel produced according to Patent Document 1, since the water content of the hydrogel is high, when the functional ingredient is applied to the hydrogel, the concentration of the active ingredient is diluted. Percutaneous transmission efficiency may be inferior. In addition, the water contained in the hydrogel can pose a risk of putrefaction due to the growth of microorganisms, and therefore can have a negative effect on the stability of the active ingredient within the effective period of the product.

As another conventional technique, in Patent Document 2 (Korean Patent Registration No. 10-1212504), polyvinyl alcohol and succinic acid are added to (Sl) distilled water, and the temperature is increased to 90 ° C. while stirring for 6 hours. The stage of producing a polyvinyl alcohol / succinic acid solution by heating; (S2) Carboxymethyl cellulose is added to the polyvinyl alcohol / succinic acid solution, and the mixture is stirred at 90 ° C. for 3 hours to prepare polyvinyl alcohol / succinic acid /. A step of producing a carboxymethyl cellulose solution; (S3) a step of adding a yellow chain extract to the polyvinyl alcohol / succinic acid / carboxymethyl cellulose solution and stirring at 90 ° C. for 30 minutes; and (S4) a step of mixing in the above step (S3). Described is a method for producing an antibacterial hydrogel comprising a step of spreading a mixture of polyvinyl alcohol / succinic acid / carboxymethyl cellulose solution and a yellow ream extract and drying at room temperature at 48% RH for 48 hours; ing.

According to the above-mentioned Patent Document 2, by reducing the water content of the hydrogel, the problem of hydrogel spoilage due to the propagation of microorganisms conventionally generated due to the high water content is solved, so that the stability is ensured. Since the problem of concentration dilution can be solved, a hydrogel that can be applied by quantifying the active ingredient can be produced. However, in order to enhance the transdermal transmission effect of hydrogel, it is necessary to develop a dosage form having a higher liquid absorption.

Korean Patent Application Publication No. 10-2014-0116325A Korean Patent No. 10-1212504B

An object to be solved by the present invention is to provide a method for producing a porous hydrogel sheet having an improved liquid absorption.

Another problem to be solved by the present invention is to provide a porous hydrogel sheet produced by the above-mentioned production method.

In order to solve the above-mentioned problems, the present invention is in the stage of producing (1) a composition solution for a hydrogel sheet containing a cellulose ether, a gelling agent, a gelation accelerator and a solvent; (2) the hydrogel sheet. Step of applying the composition solution for hydrogel sheet in the form of a sheet; (3) Step of gelling the composition solution for the hydrogel sheet applied in the form of the sheet to produce a hydrogel sheet; (4) Pre-freezing the hydrogel sheet. Steps; and (5) Provided are a method for producing a porous hydrogel sheet, which comprises a step of freezing and drying the pre-frozen hydrogel sheet.

The step (1) is a step of mixing the cellulose ether, a gelling agent and a gelation accelerator to produce a composition for a hydrogel sheet; and the composition for a hydrogel sheet is heated at 70 ° C to 100 ° C. (Hot water) can be charged and stirred to include the step of producing a composition solution for a hydrogel sheet.

Further, a defoaming step of removing air bubbles from the composition solution for hydrogel sheet produced in the step (1) can be further included.

The cellulose ethers include methyl cellulose (methyl cellulose), hydroxyethyl methyl cellulose (hydroxyethyl cellulose cellulouse), hydroxypropylmethyl cellulose (hydroxypolylyl methyl cellulose), hydroxyethyl cellulose (hydroxyethyl cellulose), and hydroxyethyl cellulose (hydroxyethyl cellulose). The gelling agent can include one or more selected from the group consisting of: Carrageenan, Locust bean gum, Mannose and water-chestnut floor. The gelation accelerator can include one or more selected from the group consisting of magnesium chloride, potassium chloride, calcium chloride and sodium chloride.

In the step (2), the composition solution for a hydrogel sheet can be cast into a sheet form while maintaining the composition solution within the range between the gelation temperature of the composition solution and the boiling point of the solvent.

The gelation temperature of the composition solution for a hydrogel sheet or the boiling point of the solvent may be 50 to 100 ° C.

In the step (3), the composition solution for a hydrogel sheet coated in the form of a sheet can be cooled and gelled to produce a hydrogel sheet.

In step (4), the pre-freezing can be performed at -196 to −15 ° C. for 5 minutes to 24 hours.

In step (5), the lyophilization can be performed at −90 to −40 ° C. for 12 to 72 hours.

The present invention also provides a porous hydrogel sheet produced by the above-mentioned production method.

The thickness of the sheet may be 0.1 to 10.0 mm.

The liquid absorption of the sheet may be 8 to 18 g / g.

The sheet is used in cosmetic mask packs or transdermal transfer formulations, or in the medical field selected from the group consisting of wound dressings and anti-adhesion agents.

According to the present invention, by providing a method for producing a hydrogel sheet including a step of pre-freezing and freeze-drying the hydrogel sheet, a porous hydrogel sheet having a low water content can be produced. Therefore, it is possible to solve the problem of water content of the conventional hydrogel, for example, the problem of diluting the concentration of the active ingredient and the problem of putrefaction of the hydrogel due to the propagation of microorganisms.

Further, since the hydrogel sheet produced by the production method of the present invention has a porous structure, it exhibits a higher liquid absorption rate than the conventional dry hydrogel sheet. Therefore, according to the present invention, it is possible to produce a porous hydrogel sheet having excellent transdermal transmission efficiency.

FIG. 1 compares the SEM image (× l00) (A) of the cross section of the hydrogel sheet produced by Example 3 and the SEM image (× 500) (B) of the cross section of the hydrogel sheet produced by Comparative Example 1. It is shown by.
FIG. 2 compares the SEM image (x100) (C) of the surface of the hydrogel sheet produced by Example 3 and the SEM image (xl00) (D) of the surface of the hydrogel sheet produced by Comparative Example 1. It is shown by.

The present invention relates to a method for producing a porous hydrogel sheet and a porous hydrogel sheet produced by the method.

First, a method for producing a porous hydrogel sheet will be described. The production method is a step of (1) producing a composition solution for a hydrogel sheet containing a cellulose ether, a gelling agent, a gelation accelerator and a solvent; (2). The step of applying the composition solution for a hydrogel sheet in the form of a sheet; (3) the step of gelling the composition solution for a hydrogel sheet applied in the form of the sheet to produce a hydrogel sheet; (4) the step of producing the hydrogel sheet. Preliminary freezing; and (5) include a step of freezing and drying the prefrozen hydrogel sheet.

Hereinafter, a method for producing a porous hydrogel sheet according to an embodiment of the present invention will be described in detail step by step.

(1) Production Stage of Composition Solution for Hydrogel Sheet This stage is a stage for producing a composition solution for a hydrogel sheet containing a cellulose ether, a gelling agent, a gelation accelerator and a solvent. As used herein, the term "composition solution for hydrogel sheet" means a liquid state in which solids are dispersed, dissolved or partially dissolved in hot water, and is a dispersion, solution or partial solution. It contains the concept of.

The step (1) is a step of mixing the cellulose ether, a gelling agent and a gelation accelerator to produce a composition for a hydrogel sheet; and the composition for a hydrogel sheet is heated at 70 ° C to 100 ° C. (Hot water) can be charged and stirred to include the step of producing a composition solution for a hydrogel sheet. When the temperature of the hot water is less than 70 ° C., the composition for the hydrogel sheet is not well dispersed and partially dissolved, which may make it difficult to produce the composition solution for the hydrogel sheet. Physical properties may deteriorate.

On the other hand, the composition for a hydrogel sheet is put into hot water and stirred to apply a physical force using a mechanical stirrer in the process of producing a composition solution for a hydrogel sheet. However, at this time, a large amount of bubbles will be generated in the solution. If the bubbles are not removed from the solution, the bubbles can interfere with the formation of the three-dimensional network of hydrogels, causing problems that reduce gel strength. Thereby, the method for producing a hydrogel sheet according to the present invention can further include a defoaming step of removing bubbles from the composition solution for a hydrogel sheet produced in the above step (1). Such a defoaming step is preferably performed at 55 to 65 ° C. for 20 to 60 minutes.

The cellulose ethers include methyl cellulose (methyl cellulose), hydroxyethyl methyl cellulose (hydroxyethyl cellulose cellulose), hydroxypropylmethyl cellulose (hydroxypropyl methyl cellulose), hydroxyethyl cellulose (hydroxyethyl cellulose), and hydroxyethyl cellulose (hydroxyethyl cellulose). It can contain one or more selected from the group consisting of.

The gelling agent is added for gel formation, strength regulation, regulation of syneresis, and improvement of usability. As such a gelling agent, it is preferable to use a natural polymer rather than a water-soluble synthetic polymer in consideration of toxicity to the skin, for example, carrageenan, locust bean gum, mannose ( It can contain one or more selected from the group consisting of Mannose) and water-chestnut floor.

The gelling accelerator serves to crosslink the gelling agent. The gelation accelerator may be a salt of a Group 1 or Group 2 metal, and may contain, for example, one or more selected from the group consisting of magnesium chloride, potassium chloride, calcium chloride and sodium chloride.

(2) Application stage of the composition solution for hydrogel sheet This stage is a stage of applying the composition solution for hydrogel sheet produced in the above step (1) in the form of a sheet.

This step can be cast in sheet form while maintaining the composition solution for hydrogel sheet within the range between the gelation temperature of the composition solution and the boiling point of the solvent.

When the temperature of the composition solution for a hydrogel sheet is lower than the gelation temperature of the solution, gelation proceeds during coating, causing a concentration deviation of solid content, resulting in surface characteristics of the final sheet. Can have a negative impact. On the other hand, when the temperature of the composition solution for a hydrogel sheet exceeds the boiling point of the solvent of the solution, the solvent evaporates and the concentration changes, so that a uniform product may not be obtained. Considering the above points, the gelation temperature of the composition solution or the boiling point of the solvent is preferably 50 to 100 ° C, more preferably 55 to 90 ° C.

Then, for the application of the composition solution for a hydrogel sheet, a commonly known method used in the art can be used without limitation, for example, a caster or a caster capable of applying the composition solution in the form of a sheet. A coating machine or the like is used. As a specific example, the coating machine is selected from the group consisting of a gravure coating machine, a comma coating machine, a slot die coating machine and a spray coating machine.

At this time, the composition solution for the hydrogel sheet is 0. It can be applied with a thickness of lmm to 10.0 mm. The thickness is 0. If it is less than lmm, the strength of the hydrogel sheet is reduced and the problem of tearing may occur. On the other hand, when the thickness exceeds l0 mm, the skin adhesion of the hydrogel sheet in a gel state is inferior, and the transmission efficiency of the active ingredient may be inferior.

(3) Gelling stage This stage is a stage for producing a hydrogel sheet by gelling the composition solution for a hydrogel sheet applied in the form of a sheet in the above step (3).

At this stage, the composition solution for a hydrogel sheet can be cooled and gelled to produce a hydrogel sheet.

At this time, the cooling can be performed by an ordinary method belonging to the field belonging to the present invention, for example, among a method using natural cooling left naturally at room temperature, a method using a cooling tunnel, and a method using these in combination. It can be done by any one method.

(4) Pre-freezing stage This stage is a stage of pre-freezing the hydrogel sheet produced in the above-mentioned step (3).

By freezing the water existing in the hydrogel sheet through the pre-freezing process to form ice crystals, and sublimating the frozen ice crystals without going through a liquid state through "(5) Freezing and drying step" described later. , A hydrogel sheet in a porous form can be obtained. If the pre-freezing step is not performed, the water content in the hydrogel sheet evaporates before it freezes, so that it is difficult to obtain a porous product.

The pre-freezing is preferably carried out at -196 to −15 ° C. for 5 minutes to 24 hours. If the pre-freezing temperature exceeds -15 ° C or the time is less than 5 minutes, the water in the hydrogel sheet is not sufficiently frozen, and it may be difficult to secure pores of a certain size or larger in the freeze-drying process. .. On the other hand, if the preliminary freezing temperature is less than -196 ° C. or the time exceeds 24 hours, the economic efficiency in comparison with energy may be inferior.

(5) Freeze-drying stage This stage is a stage in which the hydrogel sheet pre-frozen by the above-mentioned step (4) is freeze-dried. Here, freeze-drying is a method of sublimating ice by freezing an aqueous solution or a material containing a large amount of water and reducing the pressure below the water vapor pressure to obtain a porous dried product from which water has been removed. To say. Such freeze-drying can be used for long-term storage of heat-sensitive materials, which are unstable mainly when the water content is high, and a product having excellent resolubility in water can be obtained. ..

In the present invention, ice crystals present in the hydrogel sheet prefrozen through freeze-drying are sublimated into gaseous vapors, and pores are formed at the sites where the ice crystals have escaped to form porous hydro. A gel sheet is obtained.

Such freeze-drying can be performed at a temperature of −90 to −40 ° C. for 12 to 72 hours. Since the freeze-drying conditions have a great influence on the quality of the hydrogel sheet, great care must be taken in its adjustment. That is, if the conditions are not met during freeze-drying, a hydrogel sheet having a desired pore structure may not be obtained, so the freeze-drying conditions must be carefully adjusted.

On the other hand, according to the present invention, the porous hydrogel sheet produced by the above-mentioned production method is provided.

The thickness of the porous hydrogel sheet is preferably 0.1 to 10.0 mm, and the thickness is 0. If it is less than l mm, the strength may decrease and a problem of tearing may occur. On the other hand, if it exceeds 10.0 mm, the skin adhesion of the gelled hydrogel sheet is inferior and the active ingredient is transdermal. Transmission efficiency may be inferior.

Similar to the conventional dry hydrogel sheet, the porous hydrogel sheet exhibits a reversible property of gelling when impregnated with water and has a low water content, so that the stability of the active ingredient can be guaranteed. .. Further, since the hydrogel sheet according to the present invention exhibits a porous structure by freeze-drying, it exhibits a liquid absorption range of 8 to 18 g / g, which is higher than that of the conventional dried hydrogel, and has excellent transdermal transmission efficiency. show.

Such a porous hydrogel sheet can be widely applied to various products such as in the cosmetic field or the pharmaceutical field, preferably used in a cosmetic mask pack or a transdermal transfer product, or a wound dressing and an adhesion. It is used in the medical field selected from the group consisting of preventive agents. When the hydrogel sheet is used as a mask pack or transdermal transfer product, it can contain more functional active ingredients than general non-woven fabric sheets and conventional dry hydrogel sheets, and when used as a wound dressing, exudates. It is effective for absorption of.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to such examples.

<Example 1>
Hydrogel sheet composition by mixing hydroxypropylmethylcellulose (HPMC) (manufactured by Lotte Precision Chemical Co., Ltd., HPMC2910), carrageenan (MSC), locust bean gum (LBG sililia) and potassium chloride (Sigma Aldrich). Manufactured. At this time, per 1 mol of glucose unit (glucose unit) of the HPMC, the carrageenan was 0.3 mol (repeated unit standard), the locust bean gum was 0.1 mol (repeated unit standard), and the potassium chloride was 0. It was mixed at a molar ratio of 07 mol.

5 g of the composition for a hydrogel sheet is put into 95 g of hot water at 85 ° C. and stirred to produce a composition solution for a hydrogel sheet, and then the solution is stored in a constant temperature bath at 60 ° C. for 60 minutes. As a result, bubbles in the solution were floated and removed.

While maintaining the composition solution from which bubbles have been removed at 60 ° C., the solution is transferred to casters (Pl-1210, Hohsen, Japan), and the casters are used to make the composition solution uniform on a glass plate to a thickness of 0.2 mm. Was applied to.

The composition solution applied on the glass plate was cooled to room temperature by a method of natural cooling and gelled to produce a hydrogel sheet.

The hydrogel sheet was pre-frozen at −75 ° C. for 1 hour using a deep freezer (DFU-374CE, Operon, South Korea).

The pre-frozen hydrogel sheet was freeze-dried at −80 ° C. for 48 hours using a freeze-dryer (FDS8512, ilShinBioBase, South Korea) to produce a porous hydrogel sheet.

<Examples 2 to 4>
A hydrogel sheet was produced by the same method as in Example 1 except that the preliminary freezing temperature was adjusted as shown in Table 1 below.

<Comparative example l>
The hydrogel sheet gelled according to Example 1 was dried at room temperature to produce a dried hydrogel sheet.

〔Evaluation method〕
1. 1. Liquid absorption (g / g)
After cutting the porous hydrogel sheet produced by Examples 1 to 4 and the dry hydrogel sheet produced by Comparative Example 1 into a size of 50 mm × 50 mm, the initial weight of the cut hydrogel sheet was measured. Then, the hydrogel sheet was immersed in an excessive amount of purified water for 10 minutes, then taken out to remove water on the gel surface, and the weight of the absorbed hydrogel sheet was measured. After calculating the liquid absorption by the following formula 1 using each of the measured weights, the results are shown in Table 1.

Liquid absorption (g / g) = (measured weight-initial weight) / initial weight ... (1)

However, in the above formula (1), the initial weight indicates the initial weight (g) of the cut hydrogel sheet, and the measured weight indicates the weight (g) of the absorbed hydrogel sheet.

2. 2. SEM (Scanning Electron Microscope) Analysis To confirm the cross-sectional and surface structures of the porous hydrogel sheet produced by Example 3 and the dried hydrogel sheet produced by Comparative Example 1, a scanning electron microscope (SNE-3000M,). Observations were performed using SEC (Korea), and the results are shown in FIGS. 1 and 2.

Referring to Table 1, the porous hydrogel sheet produced through the preliminary freezing and freeze-drying steps according to Examples 1 to 4 of the present invention absorbs liquid as compared with the dried hydrogel sheet of Comparative Example 1 dried at room temperature. It can be confirmed that the degree appears remarkably well.

In addition, FIGS. 1 and 2 show SEM images of the cross section and the surface of the hydrogel sheet produced by Example 3 and Comparative Example 1, and with reference to these, freeze-dried Hydro of Example 3 is shown. It can be confirmed that the gel sheet has a porous cross section (A) and a surface (C), whereas the hydrogel sheet of Comparative Example 1 dried at room temperature does not show a porous structure. .. At this time, in the case of SEM images of the cross section (A) and the surface (C) manufactured by Example 3 and the surface (D) of the hydrogel sheet manufactured by Comparative Example 1 in FIGS. 1 and 2, 100. A double-magnified image was shown, and in the case of the SEM image of the cross section of the hydrogel sheet produced by Comparative Example 1, a 500-fold magnified image was shown in order to more clearly show the presence or absence of internal pores.

As described above, the examples disclosed in the present invention are not intended to limit the technical idea of the present invention, but are intended to explain the present invention, and the scope of the present invention should be understood by the following claims. It should be understood that all the technical ideas which are, and are within the same range, are included in the claims of the present invention.

Claims (10)

(1) A stage for producing a composition solution for a hydrogel sheet containing a cellulose ether, a gelling agent, a gelation accelerator and a solvent;
(2) A step of applying the composition solution for a hydrogel sheet in the form of a sheet;
(3) A stage for producing a hydrogel sheet by gelling the composition solution for a hydrogel sheet applied in the form of the sheet;
(4) A method for producing a porous hydrogel sheet, which comprises a step of pre-freezing the pre-frozen hydrogel sheet; and (5) a step of freeze-drying the pre-frozen roselle sheet.
The step (1) is a step of mixing the cellulose ether, a gelling agent and a gelation accelerator to produce a composition for a hydrogel sheet; and the composition for a hydrogel sheet is heated at 70 ° C to 100 ° C. A method for producing a porous hydrogel sheet, which comprises a step of charging into (hot water) and stirring to produce a composition solution for a hydrogel sheet. The method for producing a porous hydrogel sheet according to claim 1, further comprising a defoaming step of removing bubbles from the composition solution for a hydrogel sheet produced in the step (1). The cellulose ethers include methyl cellulose (methyl cellulose), hydroxyethyl methyl cellulose (hydroxyethyl cellulose cellulose), hydroxypropylmethyl cellulose (hydroxypropyl methyl cellulose), hydroxyethyl cellulose (hydroxyethyl cellulose), and hydroxyethyl cellulose (hydroxyethyl cellulose). The method for producing a porous hydrogel sheet according to claim 1, which comprises one or more selected from the group consisting of. The gelling agent is characterized by containing one or more selected from the group consisting of carrageenan, locust bean gum, mannose and water-chestnut floor. The method for producing a porous hydrogel sheet according to claim 1. The method for producing a porous hydrogel sheet according to claim 1, wherein the gelation accelerator contains at least one selected from the group consisting of magnesium chloride, potassium chloride, calcium chloride and sodium chloride. The step (2) is characterized in that casting is performed in the form of a sheet while maintaining the temperature of the composition solution for a hydrogel sheet within the range between the gelation temperature of the composition solution and the boiling point of the solvent. The method for producing a porous hydrogel sheet according to claim 1. The method for producing a porous hydrogel sheet according to claim 6 , wherein the gelation temperature of the composition solution for a hydrogel sheet or the boiling point of the solvent is 50 to 100 ° C. The method for producing a porous hydrogel sheet according to claim 1, wherein the step (3) is to cool and gel the composition solution for a hydrogel sheet applied in the form of the sheet. The method for producing a porous hydrogel sheet according to claim 1, wherein the pre-freezing is performed at -196 to −15 ° C. for 5 minutes to 24 hours. The method for producing a porous hydrogel sheet according to claim 1, wherein the freeze-drying is performed at −90 to −40 ° C. for 12 to 72 hours.

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