KR101609104B1

KR101609104B1 - Hydrogel patch compositions for iontophoresis, hydrogel patch containing the same and the preparing method thereof

Info

Publication number: KR101609104B1
Application number: KR1020150136745A
Authority: KR
Inventors: 송해용; 김성은; 윤영필
Original assignee: (주)오스힐; 고려대학교 산학협력단
Priority date: 2015-09-25
Filing date: 2015-09-25
Publication date: 2016-04-20

Abstract

The present invention reduces the content of polymer that maintains the physical properties of the hydrogel, increases the content of water, and induces ion migration more actively. The cross-linking and sterilization of polymer are performed simultaneously with radiation, And a hydrogel patch composition for percutaneous delivery capable of simultaneously carrying out cross-linking and sterilization of a polymer even if it does not contain a preservative, a hydrogel patch for transdermal delivery comprising the same, and a method for producing the same. According to the present invention, it is possible to produce a gel by cross-linking a polymer by a radiation treatment, and sterilization can be performed at the same time, so that it does not contain a cross-linking agent and a preservative that cause skin irritation, and has excellent skin improving effect. In particular, it is possible to provide wrinkle-improving and whitening effect at the same time, and it is possible to increase the transdermal delivery efficiency of the active ingredient through iontophoresis. In addition, So that the delivery efficiency of the active ingredient is very high.

Description

TECHNICAL FIELD The present invention relates to a hydrogel patch composition for transdermal delivery, a transdermal delivery hydrogel patch containing the composition, a hydrogel patch containing the same and a preparation method thereof,

The present invention relates to a transdermal delivery hydrogel patch composition, a transdermal delivery hydrogel patch and a preparation method thereof, and more particularly to a transdermal delivery hydrogel patch for transdermal delivery, which comprises crosslinking a polymer by physical crosslinking at low temperatures such as freezing and thawing, The present invention also relates to a hydrogel patch composition for transdermal delivery which does not contain a cross-linking agent and a preservative which can sterilize through retort sterilization at high temperature and high pressure to induce skin irritation and has an excellent skin improving effect, The present invention relates to a hydrogel patch for transdermal delivery and a method for producing the same.

The wrinkles of the skin are caused by the decrease of sebaceous glands due to aging and the resulting skin dryness and skin elasticity. In other words, skin wrinkles are caused by reduced elasticity of the collagen and dermis components of the dermis due to aging of the skin, and wrinkles are further exacerbated by absorption of subcutaneous fat. Therefore, various methods of wrinkle management are being carried out in order to restore normal skin function in addition to dermatological treatment.

The skin is equipped with physiochemical UV protection factors and has a defense mechanism that minimizes the skin disorder caused by various photochemical reactions. Among them, melanin is produced to protect the skin from ultraviolet rays. As the activity of tyrosinase is promoted in the melanin-forming cells, the melanin production increases and the skin can be blackened and the ultraviolet rays can be blocked. However, when melanin is excessively produced, skin diseases such as blackening and staining of the skin may occur due to melanin deposition.

Methods for inducing skin whitening by suppressing wrinkle improvement and production of melanin pigment include surgical methods such as peeling and botox, and cosmetic creams, lotions and mask pack products including adenosine, arbutin, ascorbic acid, There is a method to use it by attaching to or attaching to skin for a period. However, many of the side effects have been reported in the surgical method. In the non - surgical method, the penetration rate is slow due to the inability of the skin to penetrate easily, and the effect is also lower than the surgical method.

Therefore, a method designed for effective delivery of active ingredients is iontophoresis (iontophoresis). This is a method in which a minute current is caused to flow through the skin to allow an ionized nutrient or drug to be ionized by an artificial potential difference to penetrate the transdermal tissue through an electric repulsive force. This method is more effective than a method of delivering an effective ingredient by a lotion, The transdermal delivery power of the component is excellent. In addition, it is possible to control the intensity of the electric current and the application time, so that the dose of the active ingredient can be controlled.

At this time, in the case of the electrode patch used in the iontophoresis, a sheet material having a high degree of flexibility and adhesiveness to the skin such as conductive resin or conductive silicone rubber is mainly used as a patch form including an electrode for ion introduction, but the water content is low, Since the ion content is high due to the high polymer content, the release efficiency of the active ingredient is lowered, and preservatives are essentially contained for the long-term storage and distribution of patches, which may cause skin irritation. In addition, the available fires added to the crosslinking of the polymer may be a factor that may cause skin irritation.

Korean Patent Publication No. 10-2009-0101668 (2009.09.29.) Korean Registered Patent No. 10-1012289 (Feb.

SUMMARY OF THE INVENTION Accordingly, the present invention has been made in order to solve the above-mentioned problems, and it is an object of the present invention to provide a method for manufacturing a hydrogel, which is capable of reducing the content of a polymer to maintain physical properties of a hydrogel, And sterilization at the same time to provide a crosslinking agent for skin irritation and a method of preparing a hydrogel patch for transdermal delivery which can simultaneously carry out crosslinking and sterilization of a polymer even if it does not contain preservatives.

Accordingly, the present invention provides a hydrogel patch composition for transdermal delivery comprising 20 to 40 parts by weight of a gel-forming agent and 85 to 150 parts by weight of a natural product as an active ingredient, based on 100 parts by weight of the water-soluble polymer.

In one preferred embodiment of the present invention, the water-soluble polymer is selected from the group consisting of an acrylic polymer, a vinyl polymer, a cellulose derivative, an alkylene polymer, a glycol polymer, a urea polymer, a melamine polymer and an epoxy polymer And may include one or more species.

In one preferred embodiment of the present invention, the acrylic polymer is one kind selected from the group consisting of polyacrylic acid, methyl acrylate, ethyl acrylate, and butyl acrylate. Or more.

In one preferred embodiment of the present invention, the vinyl polymer may include at least one selected from the group consisting of polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl acetate, and polyvinyl chloride.

In a preferred embodiment of the present invention, the gel-forming agent is selected from the group consisting of agar, carrageenan gum, kerberine gum gum, locust gum gum, xanthan gum, cellulose gum, guar gum, gum arabic, gellan gum and gelatin Or more.

In a preferred embodiment of the present invention, the natural product may include at least one selected from the group consisting of blueberry extract, herbal extract and blackberry extract.

In one preferred embodiment of the present invention, the wrinkle-improving agent may further comprise 0.1 to 0.5 parts by weight of a wrinkle-reducing agent based on 100 parts by weight of the water-soluble polymer, wherein the wrinkle-improving agent is adenosine, ascorbyl glucoside, kinetin, auxin, Hydroxypropylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone,

In a preferred embodiment of the present invention, the whitening agent may further comprise 1.0 to 6.0 parts by weight of a whitening agent based on 100 parts by weight of the water-soluble polymer. The whitening agent may be selected from the group consisting of arbutin, niacinamide, ascorbic acid, magnesium ascorbyl phosphate, Acid-2-glucoside, mulberry extract, ethyl ascorbyl ether, and an oil-soluble licorice extract.

In one preferred embodiment of the present invention, 0.01 to 0.05 parts by weight of sodium chloride may be added to 100 parts by weight of the water-soluble polymer.

In a preferred embodiment of the present invention, the water-soluble polymer comprises polyvinyl alcohol, the gel-forming agent comprises carrageenan gum, xanthan gum and locust bean gum, the natural product comprises a blackberry extract, 10 to 20 parts by weight of carrageenan gum, 7 to 13 parts by weight of xanthan gum, 4 to 8 parts by weight of locust bean gum and 85 to 165 parts by weight of blackberry extract, based on 100 parts by weight of polyvinyl alcohol.

In a preferred embodiment of the present invention, the water-soluble polymer comprises polyvinyl alcohol, the gel-forming agent comprises carrageenan gum, xanthan gum and locust bean gum, the natural product comprises a blackberry extract, 10 to 20 parts by weight of carrageenan gum, 7 to 13 parts by weight of xanthan gum, 4 to 8 parts by weight of locust bean gum, and 85 to 165 parts by weight of blackberry extract, based on 100 parts by weight of vinyl alcohol.

In one preferred embodiment of the present invention, the hydrogel patch composition may have a viscosity ranging from 10 × 10 ⁴ to 15 × 10 ⁴ cP (27 ° C.).

Another aspect of the present invention provides a transdermal delivery hydrogel patch comprising a shaped body in which the transdermal delivery hydrogel patch composition is physically crosslinked.

In a preferred embodiment of the present invention, the hydrogel patch may have a thickness of 0.5 to 3 mm.

In a preferred embodiment of the present invention, the hydrogel patch may have an electrical conductivity of 6 × 10 ^-1 to 10 × 10 ^-1 s / cm.

In a preferred embodiment of the present invention, the hydrogel patch may have a reduction rate of the wrinkle depth of 10% or more when attached to the skin of the eye when the patch is applied for 15 to 25 minutes for 20 days or more once a day.

In a preferred embodiment of the present invention, the hydrogel patch may have a crosslinking ratio of 70% or more according to the following formula (1).

[Formula 1]

Crosslinking ratio [%] = W _d / W _i x 100

Where W _i is the weight of the hydrogel patch composition after the primary drying and W _d is the weight after the secondary drying.

In a preferred embodiment of the present invention, the hydrogel patch may have a water content of 90 to 97%.

The present invention relates to a method for preparing a mixed solution by mixing the transdermal delivery hydrogel patch composition at 60 to 70 캜, And a second step of physically crosslinking the mixed solution to prepare a hydrogel patch. The present invention also provides a method for producing a hydrogel patch for transdermal delivery.

In a preferred embodiment of the present invention, the two-stage freezing may be performed one or more times at a temperature of -75 ° C to -50 ° C for 1 to 3 hours.

In one preferred embodiment of the present invention, the crosslinked hydrogel patch in the second step may have a crosslinking ratio of 70% or more according to the following formula (1).

[Formula 1]

Crosslinking ratio [%] = Wd / Wi x 100

Here, Wi represents the weight of the hydrogel patch according to the present invention after the primary drying, and Wd represents the weight after the secondary drying.

Another aspect of the present invention provides a hydrogel patch for skin care comprising a shaped body obtained by physically crosslinking the transdermal delivery hydrogel patch composition.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to crosslink the polymer by physical crosslinking at a low temperature to prepare it in a gel form, and sterilize it by the retort sterilization method, so that it does not contain a crosslinking agent and a preservative which cause skin irritation, . In particular, it is possible to provide wrinkle-improving and whitening effect at the same time, and it is possible to increase the transdermal delivery efficiency of the active ingredient through iontophoresis. In addition, So that the delivery efficiency of the active ingredient is very high.

1 is a graph showing the crosslinking rate of a transdermal delivery hydrogel patch according to a preferred embodiment of the present invention.
2 is a graph showing the mechanical strength of a transdermal delivery hydrogel patch according to a preferred embodiment of the present invention.
FIG. 3 is a graph showing the viscosity of a transdermal delivery hydrogel patch according to a preferred embodiment of the present invention.
4 is a graph showing an electrical conductivity of a transdermal delivery hydrogel patch according to a preferred embodiment of the present invention.
FIG. 5 is a schematic view showing a reaction mechanism upon pressurization of a transdermal delivery hydrogel patch according to a preferred embodiment of the present invention. FIG.
FIG. 6 is an image showing the pressing-effect of the transdermal delivery hydrogel patch according to one preferred embodiment of the present invention.
7 is an image showing a wrinkle-reducing effect of the transdermal delivery hydrogel patch according to an embodiment of the present invention.
8 is an image showing a whitening effect of a transdermal delivery hydrogel patch according to a preferred embodiment of the present invention.

The electrode patch used in the conventional iontophoresis is a patch form including an electrode for introducing ions, and mainly a sheet material having a high degree of flexible skin adhesion such as conductive resin or conductive silicone rubber is mainly used. However, Since the ion content is high due to the high polymer content, the release efficiency of the active ingredient is lowered, and preservatives are essentially contained for the long-term storage and distribution of patches, which may cause skin irritation. In addition, the available fires added to the crosslinking of the polymer may be a factor that may cause skin irritation.

Accordingly, the present invention provides a hydrogel patch composition for transdermal delivery comprising a water-soluble polymer, a gel-forming agent, and a natural substance as an active ingredient, thereby providing a hydrogel patch composition for transdermal delivery, Gel patches can be prepared. The present invention includes physical crosslinking and retort sterilization at a low temperature by the above-mentioned components, and a cross-linking agent for inducing skin irritation and a hydrogel patch for transcutaneous delivery capable of simultaneously crosslinking and sterilizing the polymer even if the preservative is not contained therein to provide. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The transdermal delivery hydrogel patch composition according to the present invention comprises a water-soluble polymer. The water-soluble polymer can be physically crosslinked at a low temperature, and sterilized by retort sterilization, so that the gel can be prepared without containing a cross-linking agent and a preservative that cause skin irritation.

At this time, the water-soluble polymer is crosslinked through physical crosslinking at a low temperature, and is crosslinked in the form of a gel and is composed of an acrylic polymer, a vinyl polymer, a cellulose derivative, an alkylene polymer, a glycol polymer, a urea polymer, a melamine polymer and an epoxy polymer And may preferably be an acrylic polymer or a vinyl polymer.

The water-soluble polymer preferably comprises 1 to 20% by weight, more preferably 3 to 10% by weight, based on the total weight of the hydrogel patch composition for transdermal delivery. If the water-soluble polymer is contained in an amount of less than 1% by weight based on the total weight of the transdermal delivery hydrogel patch composition, the crosslinking ability may be lowered and the physical properties of the gel-state hydrogel patch may be deteriorated. There is a problem that the water containing the active ingredient is difficult to move in the gel-state hydrogel patch due to the high crosslinking ratio.

At this time, the acrylic polymer may include at least one selected from the group consisting of polyacrylic acid, methyl acrylate, ethyl acrylate, and butyl acrylate. The vinyl polymer may include at least one selected from the group consisting of polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl acetate, and polyvinyl chloride, and the cellulose derivative may be at least one selected from the group consisting of hydro-ethyl cellulose, carboxy Methylcellulose, and methylhydroxypropylcellulose, and the alkylene-based polymer may include at least one selected from the group consisting of polyalkylene glycols and polyoxyalkylene xylene And the glycol-based polymer may include at least one member selected from the group consisting of polyethylene glycol and propylene glycol. The urea-based polymer may include polyurethane, and the melamine polymer may include at least one member selected from the group consisting of hexamethoxymethyl melamine, hexa epoxymethyl melamine, and hexapentyl melamine, The epoxy-based polymer may include at least one selected from the group consisting of diclclycidyl aniline, 1,3-bis (N, N-glycidylaminomethyl) cyclohexane and ethylene glycol diclycidyl ether .

At this time, the gel-forming agent may include at least one member selected from the group consisting of agar, carrageenan gum, kerberine gum gum, locust gum gum, xanthan gum, cellulose gum, guar gum, gum arabic, gellan gum and gelatin May include carrageenan gum, locust bean gum and xanthan gum. The gel-forming agent may be included in an amount of 20 to 40 parts by weight, preferably 20 to 30 parts by weight, based on 100 parts by weight of the water-soluble polymer. When the gel-forming agent is contained in an amount of less than 20 parts by weight based on 100 parts by weight of the water-soluble polymer, physical properties of the hydrogel before the gel formation are lowered and molding is difficult. When the amount is more than 40 parts by weight, There is a problem.

The transdermal delivery hydrogel patch composition according to the present invention may further comprise a wrinkle-reducing agent, wherein the wrinkle-improving agent is selected from the group consisting of adenosine, ascorbyl glucoside, kinetin, auxin, peptide, alpha-hydroxy acid Or more, and preferably adenosine is preferably used. The wrinkle-improving agent is preferably contained in an amount of 0.5 to 2 parts by weight, preferably 0.5 to 1.5 parts by weight, based on 100 parts by weight of the water-soluble polymer. When the wrinkle-improving agent is contained in an amount of less than 0.5 parts by weight based on 100 parts by weight of the water-soluble polymer, the effect of improving wrinkles is insignificant and the duration of wrinkle improvement is shortened. When the amount is more than 3 parts by weight, skin irritation There is a problem.

The hydrogel patch composition for transdermal delivery according to the present invention may further comprise a whitening agent, and the whitening agent may be selected from the group consisting of arbutin, niacinamide, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl acid-2-glucoside, Ethyl ascorbyl ether, and an oil soluble licorice extract. Preferably, arbutin is used. The whitening agent is preferably contained in an amount of 10 to 20 parts by weight, more preferably 12 to 18 parts by weight, based on 100 parts by weight of the water-soluble polymer. When the whitening agent is contained in an amount of less than 10 parts by weight based on 100 parts by weight of the water-soluble polymer, the whitening effect is insignificant. When the whitening agent is used in an amount of more than 20 parts by weight, skin irritation may be caused and deterioration of physical properties of the hydrogel patch There is a problem.

At this time, the natural product may have at least one kind selected from the group consisting of blueberry extract, herbal extract and blackberry extract, and it is preferable to use blackberry extract. The natural product preferably contains 85 to 150 parts by weight, more preferably 100 to 150 parts by weight, based on 100 parts by weight of the water-soluble polymer. When the natural product is contained in an amount of less than 85 parts by weight based on 100 parts by weight of the water-soluble polymer, the effect of improving wrinkles is deteriorated. When the natural product is contained in an amount exceeding 150 parts by weight, the physical properties of the hydrogel patch deteriorate.

In addition, the whitening agent may further include Angelica gigas Nakai extract. The Angelica giganta extract may be contained in an amount of 20 to 50 parts by weight, and preferably 30 to 50 parts by weight, based on 100 parts by weight of the water-soluble polymer. When the Angelica keiskei radix extract is contained in an amount of less than 20 parts by weight based on 100 parts by weight of the water-soluble polymer, the whitening effect is reduced. When the angelica extract is contained in an amount of more than 50 parts by weight, the color of the hydrogel patch may be browned .

The hydrogel patch composition for transdermal delivery according to the present invention may further comprise 0.01 to 0.05 part by weight of sodium chloride relative to 100 parts by weight of the water-soluble polymer, preferably 0.03 to 0.05 part by weight of sodium chloride relative to 100 parts by weight of the water- . The sodium chloride is dissolved in purified water and exists in a charged ionic state to facilitate the flow of current. When the amount of sodium chloride is less than 0.01 part by weight based on 100 parts by weight of the water-soluble polymer, When the amount of the hydrogel is more than 0.05 part by weight, the pH of the hydrogel may be basic, which may interfere with the crosslinking reaction of the hydrogel.

In the hydrogel patch composition for transdermal delivery according to the present invention, the water-soluble polymer includes polyvinyl alcohol, the gel-forming agent includes carrageenan gum, xanthan gum and locust bean gum, and the natural product contains blackberry extract , 10 to 20 parts by weight of carrageenan gum, 7 to 13 parts by weight of xanthan gum, 4 to 8 parts by weight of locust bean gum and 85 to 165 parts by weight of blackberry extract, based on 100 parts by weight of the polyvinyl alcohol, , 10 to 15 parts by weight of carrageenan gum, 7 to 10 parts by weight of xanthan gum, 4 to 6 parts by weight of locust bean gum and 100 to 165 parts by weight of blackberry extract, based on 100 parts by weight of polyvinyl alcohol. If the pH exceeds the above range, the mechanical and electrical properties of the hydrogel patch for transdermal delivery may be deteriorated, and the water content may be lowered, resulting in a problem that migration of ions is not smooth.

The hydrogel patch composition according to the present invention may have a viscosity of 10 x 10 ⁴ cP to 15 x 10 ⁴ cP, and preferably a viscosity of 11 x 10 ⁴ cP to 15 x 10 ⁴ cP. The hydrogel patch shows a tendency to increase in viscosity as the amount of the water-soluble polymer added increases.

The present invention also provides a transdermal delivery hydrogel patch comprising a shaped article obtained by cross-linking the transdermal delivery hydrogel patch composition with radiation. The hydrogel patch can be manufactured in the form of a gel by cross-linking the polymer by radiation treatment, and sterilization can be performed at the same time. Thus, the hydrogel patch does not contain a cross-linking agent and a preservative that cause skin irritation and has excellent skin improving effect. In particular, it is possible to provide wrinkle-improving and whitening effect at the same time, and it is possible to increase the transdermal delivery efficiency of the active ingredient through iontophoresis. In addition, So that the delivery efficiency of the active ingredient is very high.

At this time, the hydrogel patch may have a crosslinking ratio of 70% or more, preferably 80% or more, according to the following formula (1). When the cross-linking ratio is less than 70%, the hydrogel patch can not be produced in a gel form, resulting in deterioration of physical properties, which makes it difficult to maintain the shape.

[Formula 1]

Crosslinking ratio [%] = W _d / W _i x 100

Where W _i is the weight of the hydrogel patch composition after the primary drying and W _d is the weight after the secondary drying. Specifically, W _i is the weight of the hydrogel patch after primary drying at 55 to 65 ° C for 40 to 60 hours, and W _d is the weight of the primary dried hydrogel patch at 55 to 65 ° C for 40 to 60 hours, It is the weight after drying.

At this time, the hydrogel patch may have a thickness of 0.5 to 3 mm, preferably 1 to 2 mm. If the thickness of the hydrogel patch is less than 0.5 mm, the ion conductivity may be increased, but the physical properties of the hydrogel patch may be deteriorated. If the thickness is more than 3 mm, the ion conductivity may be lowered, There is a problem.

The hydrogel patch may have an electrical conductivity of 6 × 10 ^-1 to 10 × 10 ^-1 s / cm, preferably an electrical conductivity of 6 × 10 ^-1 to 10 × 10 ^-1 s / cm have. At this time, the higher the content of the water-soluble polymer, the lower the electric conductivity. Thus, it is preferable to prepare the hydrogel patch using the hydrogel patch composition having the optimum concentration.

In addition, the hydrogel patch may have a water content of 90 to 97%, and preferably a water content of 95 to 97%. If the water content of the hydrogel patch is less than 90%, the ion mobility may not be smooth and the electrical conductivity may be lowered. If the hydrogel patch content exceeds 97%, the water content of the polymer decreases and the mechanical properties of the hydrogel patch deteriorate There is a problem.

In the hydrogel patch according to the present invention, the hydrogel patch may have a wrinkle depth reduction rate of 10% or more when adhered to the skin of the eye for 20 days or more for 15 to 25 minutes once a day, 25 minutes 28 days or more when attaching to the skin of the eye, the wrinkle depth reduction rate may be over 14%.

The present invention relates to a method for preparing a mixed solution by mixing the transdermal delivery hydrogel patch composition at 60 to 70 캜, And a second step of physically cross-linking and sterilizing the mixed solution to prepare a hydrogel patch. The present invention also provides a method for producing a hydrogel patch for transdermal delivery. Hereinafter, the present invention will be described in detail by steps.

The step 1 is a step of mixing the hydrogel patch composition for transdermal delivery at 60 to 70 캜 to prepare a mixed solution, and the hydrogel patch composition for transdermal delivery may be homogeneously mixed.

The second step is a step of physically crosslinking and sterilizing the mixed solution to freeze and thaw at a low temperature to physically crosslink and sterilize the hydrogel patch to produce a hydrogel patch, It is possible to prepare a hydrogel patch without additives that cause skin troubles.

At this time, the freezing can be carried out at least once at a temperature of -75 ° C to -50 ° C for 1 to 3 hours, and the mixture can be physically crosslinked by thawing at room temperature, preferably at -60 to -50 ° C The process of freezing for 1 to 2 hours can be performed 2 to 3 times to physically crosslink the mixture. If it is outside the above range, physical crosslinking of the hydrogel patch is difficult.

The sterilization is preferably performed at 100 to 150 ° C for 20 to 40 minutes, more preferably at 120 to 140 ° C for 20 to 25 minutes using the retort sterilization method. If the sterilization is performed under the above temperature and time conditions, sterilization is not sufficiently performed and the sterilization effect is difficult to sustain. If the sterilization is performed under the above conditions, the physical properties of the hydrogel patch deteriorate.

The crosslinked hydrogel patch in the step 2 may have a crosslinking ratio of 70% or more, preferably 80% or more, according to the following formula (1).

[Formula 1]

Crosslinking ratio [%] = Wd / Wi x 100

Here, Wi represents the weight of the hydrogel patch according to the present invention after the primary drying, and Wd represents the weight after the secondary drying. Specifically, W _i is the weight of the hydrogel patch after primary drying at 55 to 65 ° C for 40 to 60 hours, and W _d is the weight of the primary dried hydrogel patch at 55 to 65 ° C for 40 to 60 hours, It is the weight after drying. The crosslinking ratio represents the weight ratio of the crosslinked hydrogel patch except for the evaporation amount of the non-crosslinked polymer.

In addition, the present invention provides a hydrogel patch for skin care comprising a formed article obtained by physically crosslinking the transdermal delivery hydrogel patch composition. Can be produced by the same method as described above, and a related explanation will be omitted.

Hereinafter, the present invention will be described with reference to the following examples. The following examples are provided to illustrate the present invention, but the scope of the present invention is not limited by the following examples.

[Example 1]

Example 1. Preparation of hydrogel patch for transdermal delivery

A mixture of 41.9 g of polyvinyl alcohol (PAA), 5.6 g of carrageenan, 3.7 g of xanthan gum, 2.3 g of locust bean gum, 0.5 g of adenosine, 6.0 g of arbutin and 46.5 g of blackberry extract was mixed with a homomixer (TK Homomixer, Tokushu kika The solution was mixed with 548.5 ml of purified water, and the mixture was uniformly dispersed and mixed while being heated to 65 ° C. Then, the completely dissolved aqueous solution was coated on a foil and a release paper at room temperature, For 120 minutes, frozen and then thawed at room temperature to prepare a hydrogel-type hydrogel patch for transcutaneous delivery.

Examples 2 to 5. Preparation of hydrogel patch for transdermal delivery

A hydrogel patch for transdermal delivery was prepared in the same manner as in Example 1, except that the experiment was carried out under the composition and condition as shown in Table 1 below.

Unit (g) Example 2 Example 3 Example 4 Example 5 Composition Polyvinyl
Alcohol 41.9 41.9 41.9 41.9 Carrageenan sword 5.6 6.6 7.6 8.6 Xanthan gum 3.7 3.7 3.7 2.7 Locust Blind Sword 2.3 1.3 0.3 0.3 Blackberry extract 46.5 46.5 46.5 46.5 Angelica extract 4 4 4 4 Adenosine 0.5 0.5 0.5 0.5 Arbutin 6 6 6 6 Sodium chloride 0.05 0.05 0.05 0.05 Bridging condition Temperature (℃) -75 -75 -75 -75 Time (minutes) 60 60 60 60

Example 6: Preparation of hydrogel patch for transdermal delivery

A hydrogel patch for transdermal delivery was prepared in the same manner as in Example 2 except that the freezing and thawing in Example 2 were carried out twice under the same conditions as in Example 2 above.

Example 7. Preparation of hydrogel patch for transdermal delivery

A hydrogel patch for transcutaneous delivery was prepared in the same manner as in Example 2, except that the freezing and thawing in Example 2 were carried out three times under the same conditions as in Example 2 above.

Comparative Examples 1 to 4. Preparation of hydrogel patch for transdermal delivery

A transdermal delivery hydrogel patch was prepared in the same manner as in Example 1, except that a composition such as the ingredient contents shown in the following Table 2 was used.

ingredient Content (weight: g) Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Polyvinyl alcohol 13.9 27.9 55.9 69.9 Carrageenan sword 5.6 5.6 5.6 5.6 Xanthan gum 3.7 3.7 3.7 3.7 Locust Blind Sword 2.3 2.3 2.3 2.3 Blackberry extract 46.0 46.0 46.0 46.0 Adenosine 0.5 0.5 0.5 0.5 Arbutin 6.0 6.0 6.0 6.0

Experimental Example 1. Measurement of Crosslinking Rate of Hydrogel Patch

The crosslinking ratios of the hydrogel patches prepared in Examples 1 to 7 and Comparative Examples 1 to 4 were measured and the results are shown in Table 3 below. Specifically, the hydrogel patches of Examples 1 to 7 and Comparative Examples 1 to 4 were dried in an oven at 60 DEG C for 48 hours and the initial weight ( _W.sub.i ) was measured. The hydrogel was washed again in distilled water at room temperature for 48 hours to remove the remaining crosslinked polymer in the primary dried hydrogel patch, and then the hydrogel was again dried in an oven at 60 DEG C for 48 hours to obtain a weight (W _d ) was measured. The crosslinking rate can be measured by the weight ratio percentage after the second drying to the weight after the primary drying as shown in the following formula 1. The results are shown in Table 2 and FIG.

[Formula 1]

Crosslinking ratio [%] = W _d / W _i x 100

Example 1 Example 2 Example 3 Example 4 Example 5 Crosslinking ratio (%) 77.73 75.12 69.54 65.89 60.54 Example 6 Example 7 Crosslinking ratio (%) 81.09 91.38 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Crosslinking ratio (%) 32.48 40.45 82.99 89.32

The results are shown in Table 3 and FIG. 1, showing that the examples according to the present invention exhibit excellent crosslinking ratios as compared with those of Comparative Examples 1 and 2. Among them, Examples 1 to 2 and Examples 6 to 7 have crosslinking ratios of 70 % Or more and exhibits a relatively excellent crosslinking ratio. In this case, it was confirmed that the content of polyvinyl alcohol was relatively low in Comparative Examples 1 to 2 as compared with Examples 1 to 7, and thus, the present invention provides an optimal composition ratio for producing a hydrogel patch having excellent crosslinking ratio . In addition, it was confirmed that the crosslinking ratio of Examples 6 to 7 is the most excellent, and it is understood that the crosslinking rate is increased by performing physical crosslinking more than two times.

Therefore, it was found that the hydrogel patch for skin stimulation delivery according to the present invention exhibits the best crosslinking ratio when physical crosslinking is performed at least two times, preferably three times, in combination at an optimum composition ratio.

Experimental Example 2 Measurement of mechanical strength according to the content of polyvinyl alcohol

In order to evaluate the mechanical strength of the hydrogel patch prepared in Example 1 and Comparative Examples 1 to 4, the compressive strength was measured at room temperature using an universal material tester (Instron UTM, model 4467, Canton). At this time, the diameter of the specimen was 12 mm, the thickness was 3 mm, the cross-head speed was 5 mm / min, and the load was 5 kN. The results are shown in Table 4 and FIG.

Example 1 Example 2 Example 3 Example 4 Example 5 Compressive strength (kPa) 89.62 82.15 80.54 75.45 69.25 Example 6 Example 7 Compressive strength (kPa) 96.46 104.56 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Compressive strength (kPa) 20.32 30.25 97.31 109.93

According to Table 4 and FIG. 2, it was confirmed that the examples according to the present invention exhibited excellent compressive strength as compared with Comparative Examples 1 and 2. Among them, in Examples 1 to 3 and Examples 6 to 7, the crosslinking ratio was 80 % Or more, indicating a relatively excellent compressive strength. In this case, it was confirmed that the content of polyvinyl alcohol was relatively low in Comparative Examples 1 and 2 as compared with Examples 1 to 7, and thus the present invention provides an optimum composition ratio for producing a hydrogel patch having excellent compressive strength . In addition, it was confirmed that the compressive strengths of Examples 6 to 7 are relatively excellent, and that the compressive strength is increased by performing physical crosslinking more than two times. Therefore, it was found that the hydrogel patch for skin stimulation delivery according to the present invention exhibits the most excellent compressive strength when physical crosslinking is performed at least two times, preferably three times, in combination at an optimum composition ratio.

Experimental Example 3. Viscosity Measurement of Hydrogel Patch Composition

In order to measure the viscosity of the mixed solution of the hydrogel patch composition according to the content of the water-soluble polymer in the hydrogel patch composition according to the present invention, the following experiment was conducted. The viscosity of the mixed solution of the hydrogel patch compositions of Examples 1 to 7 and Comparative Examples 1 to 4 was measured at 30 rpm using a viscometer (Brookfield) using a spindle four times at 60 ° C. The results are shown in Table 5 and FIG. At this time, the viscosity measurement represents the average value of the test value three times in total.

Example 1 Example 2 Example 3 Example 4 Example 5 Viscosity (cP) 11.28 10.2 8.24 8.01 7.65 Example 6 Example 7 Viscosity (cP) 16.91 22.49 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Viscosity (cP) 8.29 10.12 12.18 14.86

Table 5 and FIG. 3 show the viscosities of the mixed solution of the hydrogel patch compositions prepared in Examples 1 to 7 and Comparative Examples 1 to 4, wherein the viscosity of the mixed solution increases as the content of the water-soluble polymer increases . As a result, it was found that the water-soluble polymer content in the hydrogel patch composition affected the viscosity of the hydrogel patch to be produced.

Experimental Example 4. Measurement of Electrical Conductivity of Hydrogel Patch

In order to measure the electrical conductivity of the hydrogel patch according to the present invention, the hydrogel patches of Example 1 and Comparative Examples 1 to 4 were attached to a porous separator having a structure similar to the skin, And the electrical conductivity was measured using an impedance analyzer (IM6, ZAHNER-electric, Germany) under the frequency range of 6 MHz to 1 kHz and the amplitude of ± 10 mV. The results are shown in Tables 6 and 7 4. At this time, the electric conductivity represents the average value of the total of three experiments.

Example 1 Example 2 Example 3 Example 4 Example 5 Electrical conductivity
(S / cm) 7.79 E-04 6.14 E-04 6.01 E-04 6.24 E-04 Example 6 Example 7 Electrical conductivity
(S / cm) 1.20 E-04 9.00 E-05 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Electrical conductivity
(S / cm) 1.00.E-03 1.10E-03 5.33E-04 3.27E-04

According to Table 6 and FIG. 4, when the hydrogel of 6% by weight or less is used, the electric conductivity is high because the content of the polymer is low and the water content is high. When the hydrogel of 6% by weight or more is used, the content of polyvinyl alcohol The electric conductivity was lowered. Therefore, the higher the content of the polymer, the higher the electrical resistance, which is not suitable as a hydrogel formulation for iontophoresis. That is, the lower the content of the polymer is, the higher the moisture content is, so that the water content should be higher in order for the ion movement to be smooth.

EXPERIMENTAL EXAMPLE 5. Measurement of Effective Component Release Performance of Hydrogel Patch

In order to evaluate the release performance of the hydrogel patches according to the present invention, a sample of Example 1 was attached to a watt mannier to evaluate the release performance of the blackberry extract, and classified into an experimental group to which electric and ultrasonic stimulation were applied and a non- A visual evaluation of the release of blackberry extract after stimulation was performed and the results are shown in Figures 5 and 6 below. .

According to FIG. 5 and FIG. 6, it can be confirmed that the blackberry extract is released from the electric stimulation applied sample group and the wattmann paper is observed. As a result, it is confirmed that the amount of the effective ingredient is increased when the external stimulus is applied.

Experimental Example 6. Measurement of wrinkle improvement effect by increasing transdermal absorption

The wrinkle-improving effect of the hydrogel patch prepared in Example 1 and Comparative Examples 1 to 4 was measured, and the detailed evaluation method was as follows. The wrinkle-reducing effect was measured by applying 20 g of water to the skin of the eye for 20 minutes once a day for 20 women aged 30 to 60 years old, and using a portable iontophoresis device (low frequency stimulator SFT-502, hubdic CO., LTD ) And the wrinkle depth was measured every week for up to 4 weeks after attachment. At this time, the equipment for measuring the depth of the wrinkles was skin-visioscan (VC98, Germany) of CK electronics, and the CCD camera attached to the measuring equipment was cleaned, The initial value was set and the above measurement position was designated to measure the reduction rate of the wrinkle depth after applying the cosmetic composition. At this time, the initial wrinkle depth was set to '0', the wrinkle depth reduction rate was measured as a percentage, the evaluation criteria were determined, and the average value of the measurement object was calculated and rounded to one decimal place or more. The results are shown in Table 7 and FIG.

Measurement period Example 1 Example 2 Example 3 Example 4 Example 5 1 week 5.7 5.5 5.2 5.8 5.7 2 weeks 7.2 7.2 6.5 7.1 7.2 3 weeks 10.1 9.2 9.4 9.8 9.7 4 weeks 14.7 13.2 14.4 14.5 14.2 Measurement period Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 1 week Not measurable Not measurable 2.1 1.9 2 weeks 3.6 2.4 3 weeks 5.2 4.1 4 weeks 6.3 4.9

According to Table 6, it can be seen that the hydrogel patch of Example 1 according to the present invention has a reduction rate of the wrinkle depth more improved than that of the hydrogel patch of the comparative example. These results indicate that the hydrogel patch composition according to the present invention increased the transdermal absorption efficiency of the active ingredient by iontophoresis and thus increased the wrinkle-improving effect.

Experimental Example 7. Measurement of whitening effect by increasing transdermal absorption

The whitening effect of the hydrogel prepared in Example 1 and Comparative Examples 1 to 4 was measured before and after skin application, and the detailed evaluation method was as follows. The results are shown in Table 8 and FIG.

The skin whitening effect was measured in 20 women aged 30 to 60 years. The hydrogel was attached to the front of the face for 20 minutes once a day. The photographs were taken before and after applying the skin using a camera. The results of the photographs were compared three times before and after application and the whitening effect was evaluated. More specifically, the hydrogels are applied to the skin after cleansing for 20 minutes, and the images are taken at intervals of one week, compared with the images before hydrogel application, and the pictures are taken at the same place and at the same brightness of light. At this time, the skin brightness before application is evaluated by comparing the photos after one week application and two weeks after application. The criterion was evaluated by comparing the photographs before and after application of the hydrogels, indicating that the improvement of the skin brightness was 'improved' and the improvement of the brightness was 'no effect'.

Measurement period Example 1 Example 2 Example 3 Example 4 Example 5 1 week Improving Improving Improving Improving Improving 2 weeks Improving Improving Improving Improving Improving Measurement period Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 1 week Not measurable Not measurable Improving Improving 2 weeks Improving Improving

According to Table 8, it can be seen that the hydrogel of Example 1 according to the present invention has a wrinkle depth reduction ratio higher than that of the hydrogel of the comparative examples. These results show that the hydrogel composition according to the present invention increased the transdermal absorption efficiency of the active ingredient by iontophoresis and thus increased the wrinkle-improving effect.

Experimental example 8. Skin irritation test

The skin irritation of the hydrogel patch compositions of Example 1 and Comparative Examples 1 to 4 was measured. Specifically, the skin irritation was judged by clogging with 15 subcutaneous portions of healthy male and female subjects. The results are shown in Table 9 below.

(Criteria)

0: No stimulation

1: minimal stimulus

2: Weak stimulation (erythema)

3: Severe irritation (erythema, edema)

Example 1 Example 2 Example 3 Example 4 Example 5 Skin irritation (%) 0 0 0 0 0 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Skin irritation (%) 0 0 0 0

As shown in Table 9, all of the hydrogel patches according to the present invention and the comparative examples have no stimulation to the skin and can be safely applied to the skin. These results indicate that skin irritation does not occur because the hydrogel formulation does not contain cross-linking agents and preservatives that induce cross-linking of the hydrogel by irradiation and sterilization to induce skin irritation.

Claims

In a transdermal delivery hydrogel patch composition,
The hydrogel patch composition for transdermal delivery is prepared by mixing 10 to 15 parts by weight of carrageenan gum, 7 to 10 parts by weight of xanthan gum, 4 to 6 parts by weight of locust bean gum and 100 to 150 parts by weight of blackberry extract per 100 parts by weight of polyvinyl alcohol As an active ingredient,
0.5 to 2 parts by weight of a wrinkle-improving agent, 10 to 20 parts by weight of a whitening agent and 0.01 to 0.05 part by weight of sodium chloride,
A viscosity of 10 x 10 ⁴ to 15 x 10 ⁴ cP (27 캜)
The hydrogel patch prepared by crosslinking the transdermal delivery hydrogel patch composition is a transdermal delivery hydrogel patch composition having a crosslinking ratio of 70% or more according to the following formula 1:
[Formula 1]
Crosslinking ratio [%] = W _d / W _i x 100
Here, W _i is the weight of the hydrogel patch according to the present invention after the first drying, and W _d is the weight after the second drying.

delete

The method according to claim 1,
The anti-wrinkle agent may be selected from the group consisting of adenosine, ascorbyl glucoside, kinetin, auxin, peptide, retinol, retinyl palmitate, Wherein the composition comprises at least one selected from the group consisting of Polyethoxylated Retinamide and Alpha-hydroxyl acid.

The method according to claim 1,
The whitening agent may be selected from the group consisting of arbutin, niacinamide, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl acid-2-glucoside, , Ethyl ascorbyl ether, and an extract of licorice licorice. The transdermal patch for hydrogel patch according to claim 1,

delete

A hydrogel patch for transdermal stimulation delivery comprising a shaped body obtained by physically crosslinking the transdermal delivery hydrogel patch composition of any one of claims 1, 7, and 8.

13. The method of claim 12,
Wherein the hydrogel patch has a thickness of 0.5 to 3 mm.

13. The method of claim 12,
The hydrogel patch hydrogel patch for transdermal delivery, characterized in that the electrical conductivity of ^{6 × 10 -1 ~ 10 × 10} -1 s / cm.

13. The method of claim 12,
Wherein the hydrogel patch has a reduction rate of an eye wrinkle depth of 10% or more when adhered to the skin of the eye when adhering for at least 15 days for 15 to 25 minutes once a day for at least 20 days.

delete

14. The method of claim 13,
Wherein the hydrogel patch has a water content of 90 to 97%.

Mixing the hydrogel patch composition for percutaneous delivery according to claim 11 at 60 to 70 캜 to prepare a mixed solution; And
And a second step of preparing a hydrogel patch in which the mixed solution is physically cross-linked by freezing and thawing, thereby producing a hydrogel patch for transdermal delivery.

19. The method of claim 18,
Wherein the step of performing the freezing in the second step is performed at a temperature of -75 ° C to -50 ° C for 1 to 3 hours at least once.

19. The method of claim 18,
Wherein the hydrogel patch crosslinked in step 2 has a crosslinking ratio of 70% or more according to the following formula 1:
[Formula 1]
Crosslinking ratio [%] = W _d / W _i x 100
Here, W _i is the weight of the hydrogel patch according to the present invention after the first drying, and W _d is the weight after the second drying.

A hydrogel patch for skin care comprising a shaped article obtained by physically crosslinking the transdermal delivery hydrogel patch composition of any one of claims 1, 7, and 8.