KR102686652B1 - Method of manufacturing porous hydrogel sheet and porous hydrogel sheet manufactured by the method - Google Patents

Abstract

The present invention includes the steps of (1) preparing a composition solution for a hydrogel sheet containing cellulose ether, a gelling agent, a gelling accelerator, and a solvent; (2) applying the hydrogel sheet composition solution in a sheet form; (3) manufacturing a hydrogel sheet by gelling the composition solution for a hydrogel sheet applied in the form of a sheet; (4) pre-freezing the hydrogel sheet; and (5) a method of manufacturing a porous hydrogel sheet comprising the step of freeze-drying the pre-frozen hydrogel sheet, and a hydrogel sheet manufactured according to the manufacturing method. The method for producing a hydrogel sheet according to the present invention can provide a porous hydrogel sheet with improved liquid absorption while enabling quantification and stability of the active ingredient.

Description

Method of manufacturing a porous hydrogel sheet and a porous hydrogel sheet manufactured by the method {Method of manufacturing porous hydrogel sheet and porous hydrogel sheet manufactured by the method}

The present invention relates to a method for manufacturing a porous hydrogel sheet and a porous hydrogel sheet manufactured by the method, and more specifically, to a porous hydrogel sheet with improved liquid absorption by including the steps of pre-freezing and freeze-drying the hydrogel sheet. It relates to a method of manufacturing a gel sheet and a porous hydrogel sheet manufactured by the method.

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

The hydrogel is used in medical fields such as tissue engineering, cell culture, sustained-release drug delivery system, biosensor, soft lens, medical electrode, etc. due to its unique hydrophilicity and flexibility. , In addition, its application fields are diversifying, including as an absorbent for hygiene products and as a delivery medium for beauty agents.

As a conventional technology using such hydrogel, Patent Document 1 (Korean Patent Publication No. 10-2014-0116325) discloses (a) liquid natural polymer material, plasticizer, electrolyte, functional cosmetic ingredient, preservative and water in a specific ratio; mixing with; (b) heating the mixture from step (a) to a temperature of 70 to 90° C. to produce a gel-like hydrogel composition; (c) manufacturing a gel-like hydrogel molded body by placing the heated composition in a mold. At this time, the hydrogel composition contains 0.1 to 3% by weight of Cassia Gum, a natural polymer material, 0.1 to 2% by weight of one type selected from Carrageenan Gum or Xanthan Gum, or a mixture thereof. , 5 to 30% by weight of polyhydric alcohols as plasticizers, 0.5 to 2% by weight of electrolytes, 0.1 to 10% by weight of functional cosmetic ingredients that provide skin beauty functions, 0.001 to 0.5% by weight of preservatives, and the balance of water. According to Patent Document 1, it is stated that a hydrogel film with excellent tear strength can be provided.

However, in the case of the hydrogel manufactured according to Patent Document 1, the hydrogel has a high moisture content, so when applying the functional ingredient to the hydrogel, the concentration of the active ingredient may be diluted and the transdermal delivery efficiency may be reduced. . Additionally, the moisture contained in the hydrogel may cause the risk of spoilage due to microbial growth, which may negatively affect the stability of the active ingredient within the product's shelf life.

As another conventional technique, Patent Document 2 (Korean Patent Publication No. 10-1212504) describes (S1) adding polyvinyl alcohol and succinic acid to distilled water and heating to 90°C while stirring for 6 hours to prepare a polyvinyl alcohol/succinic acid solution. manufacturing step; (S2) adding carboxymethyl cellulose to the polyvinyl alcohol/succinic acid solution and stirring at 90°C for 3 hours to prepare a polyvinyl alcohol/succinic acid/carboxymethyl cellulose solution; (S3) adding yellow lotus extract to the polyvinyl alcohol/succinic acid/carboxymethyl cellulose solution and stirring at 90°C for 30 minutes; And (S4) spreading the mixture of the polyvinyl alcohol/succinic acid/carboxymethylcellulose solution mixed in step (S3) and the yellow lotus extract and drying it for 48 hours at room temperature and 48%RH. A method for producing hydrogels is described.

According to Patent Document 2, by lowering the moisture content of the hydrogel, the problem of hydrogel corruption due to microbial growth that previously occurred due to high moisture content is resolved, thereby ensuring stability, and the concentration dilution problem is resolved, allowing the active ingredient to be Hydrogels that can be quantified and applied can be produced. However, in order to increase the transdermal delivery effect of hydrogel, the development of a formulation with higher absorption is necessary.

KR 1020140116325 A KR 101212504 B

The problem to be solved by the present invention is to provide a method for manufacturing a porous hydrogel sheet with improved liquid absorption.

Another problem to be solved by the present invention is to provide a porous hydrogel sheet manufactured according to the above manufacturing method.

In order to solve the above problems, the present invention includes the steps of (1) preparing a composition solution for a hydrogel sheet containing cellulose ether, a gelling agent, a gelling accelerator, and a solvent; (2) applying the hydrogel sheet composition solution in a sheet form; (3) manufacturing a hydrogel sheet by gelling the composition solution for a hydrogel sheet applied in the form of a sheet; (4) pre-freezing the hydrogel sheet; and (5) freeze-drying the pre-frozen hydrogel sheet.

Step (1) includes preparing a composition for a hydrogel sheet by mixing the cellulose ether, a gelling agent, and a gelling accelerator; And it may include the step of preparing a composition solution for a hydrogel sheet by adding the composition for a hydrogel sheet to hot water at 70°C to 100°C and stirring it.

In addition, a degassing process of removing air bubbles from the hydrogel sheet composition solution prepared according to step (1) may be further included.

The cellulose ether is methyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose. and carboxymethyl cellulose, and the gelling agent may include carrageenan, locust bean gum, mannose, and water chestnut powder ( The gelation accelerator may include at least one selected from the group consisting of magnesium chloride, potassium chloride, calcium chloride, and sodium chloride.

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

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

In step (3), a hydrogel sheet can be manufactured by cooling and gelling the solution of the composition for a hydrogel sheet applied in the form of a sheet.

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

In step (5), the freeze-drying may be carried out at -90 to -40°C for 12 to 72 hours.

Additionally, the present invention provides a porous hydrogel sheet manufactured according to the above manufacturing method.

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

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

The sheet can be used as a cosmetic mask pack or transdermal delivery agent, or can be used in medical fields selected from the group consisting of wound dressing and anti-adhesion agents.

According to the present invention, a porous hydrogel sheet with low moisture content can be manufactured by providing a method for manufacturing a hydrogel sheet including the steps of pre-freezing and freeze-drying the hydrogel sheet. Therefore, problems caused by the moisture contained in existing hydrogels, such as dilution of active ingredient concentration and hydrogel corruption due to microbial growth, can be solved.

In addition, the hydrogel sheet manufactured according to the manufacturing method of the present invention exhibits a porous structure and thus exhibits a higher degree of liquid absorption compared to existing dry hydrogel sheets. Therefore, according to the present invention, a porous hydrogel sheet with excellent transdermal delivery efficiency can be produced.

Figure 1 shows a comparison between the SEM image (×100) (A) of a cross section of a hydrogel sheet prepared according to Example 3 and the SEM image (×500) (B) of a cross section of a hydrogel sheet prepared according to Comparative Example 1. will be.
Figure 2 shows a comparison of the SEM image (×100) (C) of the surface of the hydrogel sheet prepared according to Example 3 and the SEM image (×100) (D) of the surface of the hydrogel sheet prepared according to Comparative Example 1. will be.

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

First, looking at the manufacturing method of a porous hydrogel sheet, the manufacturing method includes (1) preparing a composition solution for a hydrogel sheet containing a cellulose ether, a gelling agent, a gelling accelerator, and a solvent; (2) applying the hydrogel sheet composition solution in a sheet form; (3) manufacturing a hydrogel sheet by gelling the composition solution for a hydrogel sheet applied in the form of a sheet; (4) pre-freezing the hydrogel sheet; and (5) freeze-drying the pre-frozen hydrogel sheet.

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

(1) Preparation step of composition solution for hydrogel sheet

This step is to prepare a composition solution for a hydrogel sheet containing cellulose ether, a gelling agent, a gelling accelerator, and a solvent. In this specification, “composition solution for hydrogel sheet” refers to a liquid state in which solids are dispersed, dissolved, or partially dissolved in hot water, and includes the concepts of dispersion, solution, or partial solution.

Step (1) includes preparing a composition for a hydrogel sheet by mixing the cellulose ether, a gelling agent, and a gelling accelerator; And it may include the step of preparing a composition solution for a hydrogel sheet by adding the composition for a hydrogel sheet to hot water at 70°C to 100°C and stirring it. If the temperature of the hot water is less than 70°C, dispersion and partial dissolution of the composition for the hydrogel sheet may be difficult, making it difficult to prepare a solution for the composition for the hydrogel sheet, and this may deteriorate the physical properties of the hydrogel sheet.

Meanwhile, in the process of preparing the composition solution for hydrogel sheets by adding the composition for hydrogel sheets to hot water and stirring, physical force is applied using a mechanical stirrer. At this time, a large amount of bubbles are in the solution. It happens. If air bubbles are not removed from the solution, the bubbles may interfere with the formation of a three-dimensional network structure of the hydrogel, causing a problem of lowering gel strength. Accordingly, the method for producing a hydrogel sheet according to the present invention may further include a degassing process for removing air bubbles from the solution of the composition for a hydrogel sheet prepared according to step (1) above. This degassing process is preferably performed at 55 to 65°C for 20 to 60 minutes.

The cellulose ether is methyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose. and carboxymethyl cellulose.

The gelling agent is added to form a gel, control strength, control syneresis, and improve feeling of use. As such gelling agents, it is preferable to use natural polymers rather than water-soluble synthetic polymers in consideration of their toxicity to the skin, such as carrageenan, locust bean gum, mannose, and water chestnut powder. -chestnut flour) may be included.

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

(2) Application step of composition solution for hydrogel sheet

This step is a step of applying the hydrogel sheet composition solution prepared according to step (1) above in the form of a sheet.

In this step, the hydrogel sheet composition solution may be cast into a sheet form while maintaining the range between the gelation temperature of the composition solution and the boiling point of the solvent.

If the temperature of the solution for the hydrogel sheet composition is lower than the gelation temperature of the solution, gelation progresses during application, resulting in a deviation in solid content concentration, which may have a negative effect on the final sheet surface characteristics. On the other hand, if the temperature of the hydrogel sheet composition solution exceeds the boiling point of the solvent of the solution, the solvent evaporates and the concentration changes, so there is a risk of not obtaining a uniform product. Considering the above points, the gelation temperature of the composition solution or the boiling point of the solvent may be preferably 50 to 100°C, and more preferably 55 to 90°C.

In addition, the application of the composition solution for the hydrogel sheet can be done without limitation by any known method used in the art. For example, a caster or a coater capable of applying the composition solution in the form of a sheet can be used. . As a specific example, the coating machine may be selected from the group consisting of a gravure coater, a comma coater, a slot die coater, and a spray coater.

At this time, the composition solution for the hydrogel sheet may be applied to a thickness of 0.1 mm to 10.0 mm. If the thickness is less than 0.1 mm, the strength of the hydrogel sheet may decrease and tearing may occur. On the other hand, if the thickness exceeds 10 mm, the skin adhesion of the hydrogel sheet in a gel state may decrease and the delivery efficiency of the active ingredient may decrease.

(3) Gelation step

This step is to manufacture a hydrogel sheet by gelling the composition solution for a hydrogel sheet applied in a sheet form according to step (3) above.

In this step, the hydrogel sheet composition solution can be cooled and gelled to produce a hydrogel sheet.

At this time, the cooling may be performed according to a conventional method belonging to the field belonging to the present invention, for example, a method selected from a method using natural cooling left at room temperature, a method using a cooling tunnel, and a method of using these together. It can be performed as:

(4) Preliminary freezing step

This step is to pre-freeze the hydrogel sheet prepared according to step (3) above.

Through the preliminary freezing process, the moisture present in the hydrogel sheet is frozen to form ice crystals, and through the "(5) freeze-drying step" described later, the frozen ice crystals are sublimated without going through the liquid state to form a porous form. You can obtain a hydrogel sheet. If this preliminary freezing step is not performed, the moisture in the hydrogel sheet evaporates before freezing, making it difficult to obtain a porous result.

The preliminary 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 moisture in the hydrogel sheet is not sufficiently frozen, making it difficult to secure pores of a certain size or larger during the freeze-drying process. On the other hand, if the preliminary freezing temperature is less than -196°C or the time exceeds 24 hours, there is a risk that economic efficiency relative to energy will decrease.

(5) Freeze-drying step

This step is to freeze-dry the hydrogel sheet pre-frozen according to step (4) above. Here, freeze-drying refers to a method of obtaining a porous dried product from which moisture has been removed by freezing an aqueous solution or material containing a large amount of moisture and sublimating the ice by reducing the pressure below the water vapor pressure. This freeze-drying can be mainly used for long-term storage of materials that are unstable and sensitive to heat when there is a lot of moisture, and can produce products with excellent re-solubility in water.

In the present invention, the ice crystals present in the pre-frozen hydrogel sheet are sublimated into gaseous vapor through freeze-drying, and pores are formed in the places where the ice crystals escape, forming a porous hydrogel sheet. is obtained.

This freeze drying can be carried out for 12 to 72 hours at a temperature of -90 to -40°C. Since the freeze-drying conditions greatly affect the quality of the hydrogel sheet, careful attention is required to control them. In other words, if the above conditions are exceeded during freeze-drying, there is a risk that a hydrogel sheet with the desired pore structure may not be obtained, so the freeze-drying conditions must be carefully controlled.

Meanwhile, according to the present invention, a porous hydrogel sheet manufactured according to the above manufacturing method is provided.

The thickness of the porous hydrogel sheet is preferably 0.1 to 10.0 mm. If the thickness is less than 0.1 mm, the strength may decrease and tearing problems may occur, whereas if it exceeds 10.0 mm, the hydrogel in a gel state The sheet's adhesion to the skin may decrease and the transdermal delivery efficiency of the active ingredient may decrease.

The porous hydrogel sheet, like a conventional dry hydrogel sheet, exhibits a reversible property of gelling when impregnated with water, and has a low moisture content, thereby ensuring the stability of the active ingredient. In addition, since the hydrogel sheet according to the present invention exhibits a porous structure by freeze-drying, it exhibits a high liquid absorption in the range of 8 to 18 g/g compared to existing dry hydrogels and exhibits excellent transdermal delivery efficiency.

This porous hydrogel sheet can be widely applied to various products in the cosmetics or pharmaceutical fields, and can preferably be used as a cosmetic mask pack or transdermal delivery agent, or as a wound coating material and an anti-adhesion agent selected from the group consisting of an anti-adhesion agent. It can be used in medical fields. When the hydrogel sheet is used as a mask pack or transdermal delivery agent, it can contain more functional active ingredients than a general non-woven sheet or existing dry hydrogel sheet, and when used as a wound dressing, it is effective in absorbing exudate.

Hereinafter, the present invention will be described in more detail through examples, but the present invention is not limited to these examples.

Example 1

A composition for a hydrogel sheet was prepared by mixing hydroxypropyl methyl cellulose (HPMC) (HPMC 2910, manufactured by Lotte Fine Chemical Co., Ltd.), carrageenan (MSC), locust bean gum (LBG sicilia), and potassium chloride (Sigma Aldrich). Manufactured. At this time, per 1 mole of glucose unit of the HPMC, the carrageenan was mixed at a molar ratio of 0.3 mole (based on the repeating unit), the locust bean gum was 0.1 mole (based on the repeating unit), and the potassium chloride was mixed at a molar ratio of 0.07 mole.

5 g of the composition for hydrogel sheets was added to 95 g of hot water at 85°C and stirred to prepare a composition solution for hydrogel sheets, and then the solution was stored in a constant temperature bath at 60°C for 60 minutes to remove air bubbles in the solution. It was levitated and removed.

The composition solution from which the bubbles were removed was transferred to a caster (PI-1210, Hohsen, Japan) while maintaining the temperature at 60°C, and was uniformly applied to a glass plate with a thickness of 0.2 mm using the caster.

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

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

The pre-frozen hydrogel sheet was freeze-dried at -80°C for 48 hours using a freeze dryer (FDS8512, Ilshin Biobase, Korea) to prepare a porous hydrogel sheet.

Examples 2 to 4

A hydrogel sheet was manufactured in the same manner as Example 1, except that the preliminary freezing temperature was adjusted as shown in Table 1 below.

Comparative Example 1

A dry hydrogel sheet was prepared by drying the gelled hydrogel sheet at room temperature according to Example 1.

< Evaluation method >

1. Liquid absorption (g/g)

The porous hydrogel sheet prepared according to Examples 1 to 4 and the dry hydrogel sheet prepared according to Comparative Example 1 were cut to a size of 50 mm × 50 mm, and then 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, taken out, moisture on the gel surface was removed, and the weight of the absorbed hydrogel sheet was measured. The liquid absorption degree was calculated according to Equation 1 below using each of the measured weights, and the results are shown in Table 1.

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

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

2. SEM (Scanning Electron Microscope) analysis

In order to confirm the cross-section and surface structure of the porous hydrogel sheet prepared according to Example 3 and the dry hydrogel sheet prepared according to Comparative Example 1, observation was made using a scanning electron microscope (SNE-3000M, SEC, Korea). and the results are shown in Figures 1 and 2.

Pre-freezing temperature (℃) Liquid absorption (g/g) Example 1 -75 11.03 Example 2 -55 12.14 Example 3 -35 11.79 Example 4 -15 11.30 Comparative Example 1 No preliminary freezing 6.74

Looking at Table 1, in the case of the porous hydrogel sheet manufactured through pre-freezing and freeze-drying steps according to Examples 1 to 4 of the present invention, the degree of liquid absorption was significantly higher than that of the dried hydrogel sheet of Comparative Example 1 dried at room temperature. You can see that it appears excellent.

In addition, Figures 1 and 2 show cross-sectional and surface SEM images of the hydrogel sheet prepared according to Example 3 and Comparative Example 1, and looking at these, the freeze-dried hydrogel sheet of Example 3 shows a porous cross-section ( While it has A) and surface (C), it can be seen that the hydrogel sheet of Comparative Example 1 dried at room temperature does not exhibit a porous structure. At this time, in the case of the SEM image of the cross section (A), surface (C) prepared according to Example 3, and surface (D) of the hydrogel sheet prepared according to Comparative Example 1 in FIGS. 1 and 2, the image is magnified 100 times. In the case of the cross-sectional SEM image of the hydrogel sheet prepared according to Comparative Example 1, the image was magnified 500 times to more clearly indicate whether there were internal pores.

As mentioned above, the embodiments disclosed in the present invention are not intended to limit the technical idea of the present invention, but rather to explain it, and the scope of the present invention should be interpreted in accordance with the scope of the patent claims below and all technical ideas within the equivalent scope thereof. should be interpreted as included in the scope of rights of the present invention.

Claims (16)

(1) preparing a composition solution for a hydrogel sheet containing cellulose ether, a gelling agent, a gelling accelerator, and a solvent;
(2) applying the hydrogel sheet composition solution in a sheet form;
(3) manufacturing a hydrogel sheet by gelling the composition solution for a hydrogel sheet applied in the form of a sheet;
(4) pre-freezing the hydrogel sheet; and
(5) comprising the step of freeze-drying the pre-frozen hydrogel sheet,
Step (2) is casting the hydrogel sheet composition solution into a sheet form while maintaining the temperature in a range between the gelation temperature of the composition solution and the boiling point of the solvent,
The preliminary freezing is carried out at -196 to -15°C for 5 minutes to 24 hours,
The freeze-drying is carried out at -90 to -40°C for 12 to 72 hours,
Method for manufacturing porous hydrogel sheet. According to paragraph 1,
A method for producing a porous hydrogel sheet, characterized in that it further comprises a degassing process of removing air bubbles from the solution of the composition for a hydrogel sheet prepared according to step (1). According to paragraph 1,
Step (1) includes preparing a composition for a hydrogel sheet by mixing the cellulose ether, a gelling agent, and a gelling accelerator; And a method for producing a porous hydrogel sheet, comprising the step of preparing a composition solution for a hydrogel sheet by adding the composition for a hydrogel sheet to hot water at a temperature of 70°C to 100°C and stirring it. According to paragraph 1,
The cellulose ethers include methyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose. And a method for producing a porous hydrogel sheet, comprising at least one selected from the group consisting of carboxymethyl cellulose. According to paragraph 1,
The gelling agent is a porous hydrogel comprising at least one selected from the group consisting of carrageenan, locust bean gum, mannose, and water-chestnut flour. Method for manufacturing gel sheets. According to paragraph 1,
A method for producing a porous hydrogel sheet, wherein the gelation accelerator includes at least one selected from the group consisting of magnesium chloride, potassium chloride, calcium chloride, and sodium chloride. delete According to paragraph 1,
A method for producing a porous hydrogel sheet, characterized in that the gelation temperature of the composition solution for the hydrogel sheet and the boiling point of the solvent are 50 to 100°C. According to paragraph 1,
The step (3) is a method of producing a porous hydrogel sheet, characterized in that the solution of the composition for a hydrogel sheet applied in the form of a sheet is cooled and gelled. delete delete A porous hydrogel sheet manufactured according to the manufacturing method of any one of claims 1 to 6, 8, and 9. According to clause 12,
A porous hydrogel sheet, characterized in that the thickness of the sheet is 0.1 to 10.0 mm. According to clause 12,
A porous hydrogel sheet, characterized in that the sheet has a liquid absorption of 8 to 18 g/g. According to clause 12,
A porous hydrogel sheet, characterized in that the sheet is used as a cosmetic mask pack or transdermal delivery agent. According to clause 12,
A porous hydrogel sheet, characterized in that the sheet is used in medical fields selected from the group consisting of wound dressings and anti-adhesion agents.