KR100772494B1 - Therapeutic hydrogels for atopic dermatitis using irradiation - Google Patents

Abstract

An atopic dermatitis therapeutic hydrogel is provided to inhibit the moisture release, continuously deliver drugs, adequately absorb percolate, show excellent gel strength, prevent the infection by bacteria and satisfy the storage property and sterilizing effect, thereby being effectively used for atopic dermatitis. A hydrogel for treating atopic dermatitis through irradiation is prepared by a method comprising the steps of: (a) after dissolving 1-50 wt.% of a biocompatible polymer and 1-20 wt.% of a polyhydric alcohol in 1-10 wt.% of at least one extract of a plant medicinal herb selected from the group consisting of Houttuynia cordata, persimmon leaves, Chelidonium majus var. asiaticum, pine needles, Canavalia gladiata, rosemary, lavender, spearmint, chamomile and rooibos, casting the solution; (b) freeze-drying the casted gel at a temperature of -100 to -15 deg.C and thawing it at a temperature of 5-50 deg.C; and (c) applying radioactive rays to the thawed hydrogel to crosslink and sterilize.

Description

Therapeutic hydrogels for atopic dermatitis using irradiation}

1 is a view showing a method for testing a contact dermatitis animal according to an embodiment of the present invention ((a): control group not treated with hydrogel; (b): experimental group treated with hydrogel; DNFB: 2,4-D Nitrofluorobenzene h: hours (eg h1 is 1 hour).

Figure 2 is a photograph showing the degree of back edema in mice with contact dermatitis over time with or without hydrogel treatment according to an embodiment of the present invention ((a): a control group not treated with hydrogel; (b): hydrogel Treated group).

3 is an ear edema measurement picture of a mouse with contact dermatitis according to an embodiment of the present invention.

: DNFB만 사용하였을 때;

: DNFB를 사용 후, 수화겔 처리를 하였을 때; DNFB: 2,4-디니트로플루오로벤젠). Figure 4 is a graph showing the degree of ear edema in mice with contact dermatitis over time with or without pre-treatment of the hydrogel according to an embodiment of the present invention (

When only DNFB is used;

: Hydrogel treatment after use of DNFB; DNFB: 2,4-dinitrofluorobenzene).

5 is a photograph of a mouse having atopic dermatitis according to an embodiment of the present invention (compound 48/80: polypolymer of N-methyl-p-methoxyphenethylamine and formaldehyde).

: 아무것도 투여하지 않을 때(대조군);

: compound 48/80을 투여하였을 때;

: 수화겔 전처리 후 compound 48/80을 투여하였을 때; compound 48/80: N-메틸-p-메톡시페네틸아민과 포름알데히드의 다중합체). FIG. 6 is a graph showing the number of times of scratching of mice with atopic dermatitis over time with or without pre-treatment of hydrogel according to one embodiment of the present invention (

: When nothing is administered (control);

when compound 48/80 is administered;

: When compound 48/80 was administered after hydrogel pretreatment; compound 48/80: polypolymer of N-methyl-p-methoxyphenethylamine and formaldehyde).

The present invention relates to a hydrogel for treating atopic dermatitis, comprising a biocompatible polymer, a polyhydric alcohol, and a medicinal plant extract.

Atopic disorders generally involve allergic reactions, atopic dermatitis, chronic or recurrent dermatitis, with a genetic predisposition with the characteristic shape and distribution of skin lesions and a personal or family history of atopic dermatitis. In other words, atopic dermatitis is a very common skin disease that occurs when born. Most infants or infants begin in the form of a stool, especially around 2 months of age, with about 50% occurring before 2 years of age and showing symptoms before 5 years of age. It is known that the first symptoms of adulthood are very rare, and most of them are accompanied by growth and alleviation or disappearance, and half of infants who develop infants improve before 2 years of age.

The symptoms of atopic dermatitis include pruritus (itch), chronic skin dryness, exudates, elution, and the formation of dermabrasion, double skin dermabrasion, deprivation, etc., which is caused by pruritus and may cause secondary bacterial infection. In addition, atopic dermatitis is mostly accompanied by dry skin, dry skin exacerbates pruritus, and skin irritation caused by pruritus worsens atopic dermatitis. Therefore, it is important to prevent dry skin in order to treat atopic dermatitis.

The exact pathophysiology of the atopic dermatitis is not yet fully understood, but it is thought that immunological and non-immunological mechanisms may be involved with genetic predisposition. Exogenous atopic dermatitis, which accounts for the majority of atopic dermatitis, is caused by an immune mechanism associated with immunoglobulin E (IgE), and many reports indicate that the primary immune response is caused by T-cell abnormalities rather than a secondary immune response to a particular allergen. As cell-mediated immune dysfunction is associated with an increase in immunoglobulin E in patients with atopic dermatitis, there are increasing reports claiming that the primary immune response is involved in the pathogenesis of atopic dermatitis in addition to the secondary immune response (Kee Young, et al. , Korean Medicine, Seoul, 2001, pp23-52).

In patients with atopic dermatitis, up to 80% of cell-mediated immune disorders are known to occur, and sensitivity to skin infections caused by viruses and skin filaments is increased and sensitivity to contact allergens tends to decrease. In the past, T-cell maturation deficiency and the decrease of CD8 + inhibitory T-cells have been reported, but recently, the role of CD4 + T-cells is known to be more important. In other words, T-cells secreting interleukin 4, 5 that induces or promotes the production of immunoglobulin E from B cells, and interleukin 6 that amplify are Th2 cells among CD4 + T-cells, which are Th1 cells in the skin of atopic patients. It was found that Th2 cells were present higher than that of the cells. These cytokines stimulate immune cells such as mast cells, macrophages and basophils to promote secretion of histamine, leukotrien, prostaglandin and nitric oxide (NO). These inflammatory mediators are known to promote skin inflammation.

In view of the etiology, mechanisms, and symptoms of atopic dermatitis as described above, a therapeutic agent for atopic dermatitis has been developed. As a result, a large number of natural or synthetic immunosuppressants, steroids, and antihistamines have been developed. However, steroids and antihistamines, which are conventionally used as treatments for atopic dermatitis, have the effect of temporarily relieving symptoms but do not maintain a sustained effect.

In addition, one of the important things to treat atopic dermatitis is to prevent drying of the skin, such as moisturizers such as bees wax, glycerine, propylene glycol, fatty acids, etc. Does not effectively control the evaporation of water and cannot effectively maintain the moisturizing effect.

On the other hand, the hydrogel is a material used for the purpose of burn treatment or skin regeneration that requires a constant wet state can be used for this purpose only if the hydrogel contains usually 60% or more moisture. The hydrogel has affinity with blood, body fluids and biological tissues and can be used as a wound dressing, and can also be used for contact lenses and cartilage.

In order to produce a hydrogel that can be used for this purpose, the selection of a polymer capable of forming a hydrogel must be preceded. The polymer should have a three-dimensional network structure, including water-including a hydrophilic functional group, such as -carboxyl group (COOH), -amide group (CONH ₂ ), -amide group (CONH), -sulfonic acid group (SO ₃ H). Absorption should not dissolve in water. More specifically, the polymers that can be used in the hydrogel absorb water by capillary and osmotic phenomena due to the nature of the structure and contain water, and due to the covalent structure between the polymer chains as well as electrostatic and lipophilic interactions. It should be characterized by its insoluble in water.

In general, the polymer used in the hydrogel is made of synthetic polymer, natural polymer or a mixture thereof, and the synthetic polymer is hydrophilic synthesis of polyvinyl alcohol, polyethylene oxide, polyhydroxyethyl methacrylate, polyvinylpyrrolidone and the like. The polymer may be selected and used, and the natural polymer may be selected from carrageenan, gelatin, agar (agar), alginate, collagen, chitosan, and the like.

Methods of preparing such hydrogels include chemical methods and methods using irradiation technology. Among them, by irradiating radiation rather than a chemical method prepared by adding a chemical cross-linking agent or initiator, it is not necessary to remove the chemical cross-linking agent or initiator, solves the toxicity problem due to the remaining of these substances, and can crosslink and sterilize at the same time The use of radiation technology is drawing attention. In addition, the method using the irradiation technique has the advantage that not only do not apply heat in the cross-linking process, but also can be cross-linked even in the frozen state, it is possible to freely adjust the physical properties only by adjusting the radiation dose without changing the composition.

As a conventional technique for the hydrogel, step of preparing an aqueous solution by mixing a polyvinylpyrrolidone synthetic polymer with chitosan, chitosan and polyethylene oxide, or sodium alginate and polyethylene oxide in Korea Patent Publication No. 2001-0086864 (step 1 ); Molding the aqueous solution of step 1 into a sheet form (step 2); Packing the sheet of step 2 (step 3); And irradiating the packaged sheet of step 3 with radiation (step 4) to disclose a method for preparing a hydrogel dressing for wound treatment.

In addition, Korean Patent Publication No. 2003-0060458 discloses an aqueous solution of a biocompatible polymer selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, and chitosan, and mixtures thereof, or an aqueous solution of a mixture of the biocompatible polymer and glycerin. Applying onto the membrane and performing freezing and thawing to form a prehydrogel; Packaging the preformed hydrogel on the membrane using a packaging material; And a method for preparing a wound hydrogel prepared by irradiating the packaged preliminary hydrogel with radiation.

Furthermore, Korean Patent Publication No. 2004-0085646 discloses a hydrogel dressing, a tray, and a method of preparing the same by irradiation with a composition comprising polyvinylpyrrolidone, polyhydric alcohol, and carrageenan, and a wound dressing or skin care pack using the same. Started.

However, there are no examples of hydrogels applied for the treatment of atopic dermatitis.

Therefore, the present inventors use a radiation crosslinking technique and the hydrogel containing the medicinal plant extract does not cause side effects, and the moisture and drugs are continuously and effectively supplied, and the polymer membrane is attached to the epidermal layer of the hydrogel so that it is prevented from scratching and caused by scratching. The present invention has been accomplished by preventing secondary wounds and confirming that it can be usefully used for treating atopic dermatitis.

An object of the present invention is to provide a hydrogel for treating atopic dermatitis by irradiation.

In order to achieve the above object, the present invention provides a hydrogel for treating atopic dermatitis by irradiation.

Hereinafter, the present invention will be described in detail.

The present invention provides a hydrogel for treating atopic dermatitis, comprising a biocompatible polymer, a polyhydric alcohol, and a medicinal plant extract.

In the hydrogel according to the present invention, the content of the biocompatible polymer is 1 to 50% by weight, the content of polyhydric alcohol is 1 to 20% by weight, and the content of the medicinal plant extract is preferably 1 to 10% by weight.

In the hydrogel according to the present invention, the biocompatible polymer should have a three-dimensional network structure and include a hydrophilic functional group to absorb water as well as to be insoluble in water. Therefore, the biocompatible polymer constituting the hydrogel is composed of a synthetic polymer such as polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, polyethylene oxide, or a natural polymer such as sodium carboxymethyl cellulose, gelatin, agar, alginate, chitosan, or the like. Any one polymer selected from the group may be used alone or in combination of two or more polymers, preferably polyvinyl alcohol alone, or polyvinylpyrrolidone or a mixture of polyacrylic acid and carrageenan. At this time, from the viewpoint of maintaining the strength of the hydrogel properly, the content of the polyvinyl alcohol is 1 to 50% by weight, the content of polyvinylpyrrolidone is 1 to 30% by weight, the content of polyacrylic acid is 1 ~ 20 wt%, and the content of carrageenan is preferably 1 to 5 wt%.

Specifically, the polyvinyl alcohol is a hydrophilic polymer, which is suitable as a biomaterial, has excellent mechanical and thermal strength, and can be crosslinked by a physical method after performing freezing and thawing several times, to prepare various hydrogels and membranes. Mainly used for manufacturing.

The polyvinylpyrrolidone is widely used as a biomaterial as a hydrophilic polymer and a biocompatible polymer. In addition, since polyvinylpyrrolidone contains oxygen and nitrogen in the unit structure, the polyvinylpyrrolidone can hydrogen bond with water molecules, thereby forming a network structure, which contains a large amount of water, which is suitable for treating atopic dermatitis. It is a polymer.

The carrageenan is a natural polymer, which is completely harmless to the skin, and has a characteristic of softening and calming the skin and preventing skin redness.

The other biopolymers also have a three-dimensional network structure, which is excellent in the ability to contain moisture.

In addition, in the hydrogel according to the present invention, the polyhydric alcohol serves to improve the adhesion and flexibility of the hydrogel of the present invention. However, it is required that there is no toxicity to the living body. The polyhydric alcohol is preferably composed of one or more selected from alcohols such as glycerin, ethylene glycol, propylene glycol, 1-3-butylene glycol, hexylene glycol, sorbitol, mannitol, polyethylene glycol, among which glycerin is More preferred.

In addition, in the hydrogel according to the present invention, the medicinal plant extract can be used if it is a plant extract that is effective in atopic dermatitis, such as itching and inflammation, preferably aloe vera, persimmon leaf, celandine, pine needles, bean beans, rosemary, lavender, spear It may be one or more mixed extracts selected from herbs such as mint, chamomile, rooibos and the like.

The mixing ratio of the medicinal plants in the mixed extract is 5 to 25% by weight, 5 to 25% by weight persimmon leaf, 5 to 25% by weight of celandine grass, 5 to 25% by weight pine needles, 5 to 10% by weight bean, and 5 to 30 herbs. It is preferable that it is weight%. The medicinal plant extracts can be used according to methods well known in the art or those that are commercially available.

Medicinal plants according to the present invention can be used without limitation, such as cultivated or commercially available, it is used to wash clean. The dried medicinal plant is ground to an appropriate size and put in an extraction container, and an appropriate amount of distilled water or an organic solvent is added thereto. After extracting it for 24 to 36 hours at an appropriate temperature, it can be filtered with a filter paper and the like to obtain a medicinal plant extract according to the present invention.

At this time, the distilled water is preferably tertiary distilled water, the organic solvent may be preferably used ethanol.

The extraction temperature is preferably 80 to 100 ° C. when the solvent is distilled water, and 50 to 70 ° C. for the organic solvent.

In the case of extracting with the organic solvent, after extraction, the solid is filtered and then used after removing the organic solvent component using a vacuum evaporator or the like.

The non-dried medicinal plants can be extracted in the same manner as the dried medicinal plants extract except that the juice is put into distilled water.

Since the extract prepared by the method as described above is a natural ingredient, there is no irritation to the human body and is effective in atopic dermatitis.

A hydrogel for treating atopic dermatitis according to an embodiment of the present invention,

Dissolving the biocompatible polymer and the polyhydric alcohol in the medicinal plant extract and then casting (step a);

Freezing and thawing the gel cast in step a) (step b); And

It can be prepared by a method comprising the step of crosslinking and sterilizing (step c) by irradiating the hydrogel thawed in step b) with radiation.

Step a) is a step of dissolving the biocompatible polymer and polyhydric alcohol in the medicinal plant extract, and then casting.

At this time, the content of the biocompatible polymer contained in the aqueous solution of the biocompatible polymer is preferably adjusted to a concentration of 1 to 50% by weight relative to the total aqueous solution, in order to maintain the gel strength appropriately. When the content of the biocompatible polymer is less than 1% by weight, it is impossible to maintain the gel strength enough to accommodate the drug for treating the wound, and when it exceeds 50% by weight, it is difficult to prepare an aqueous solution.

In addition, the content of the polyhydric alcohol is preferably 1 to 20% by weight based on the total aqueous solution. When the content of the polyhydric alcohol is less than 1% by weight, the adhesion and flexibility cannot be sufficiently improved, and when the content of the polyhydric alcohol is more than 20% by weight, the gel strength sufficient to accommodate the drug cannot be maintained.

Step b) freezes and thaws the gel cast and formed in step a).

Physical freezing can be introduced into the cast gel through the freezing and thawing process. At this time, it is preferable that the thickness of the hydrogel layer is properly adjusted, and more preferably adjusted to a thickness of 1 to 5 mm. In order to form effective physical crosslinking, the freezing temperature is preferably in the range of -100 to -15 ° C, more preferably -70 to -40 ° C. Further, for the same purpose, the thawing temperature is preferably in the range of 5 to 50 ° C, more preferably in the range of 20 to 30 ° C.

Freezing at temperatures lower than -100 ° C has no significant difference in the formation of physical crosslinks, while the hydrogel is not frozen at temperatures higher than -15 ° C. In addition, there is a problem in that a proper thawing time cannot be secured at a thawing temperature lower than 5 ° C., and the physical crosslinking can be weakened at a thawing temperature higher than 50 ° C.

The time for performing the freezing process may be changed depending on the freezing temperature, usually 5 minutes to 1 hour is preferred. If the freezing time is less than 5 minutes, effective freezing may not be achieved, and if the freezing time is more than 1 hour, only unnecessary waste of time is caused in the hydrogel manufacturing process.

The freezing and thawing process may be repeated to ensure stable physical crosslinking. The number of times performed is preferably 1 to 10 times, and about 1 to 3 times is preferable for the simplification of the process.

Next, step c) is a step of crosslinking and sterilizing by irradiating the hydrogel thawed in step b) with radiation.

The hydrogel formed by the irradiation has the advantage that there is no problem of residual toxicity present in the hydrogel produced by the chemical method, and at the same time crosslinking and sterilization effect can be obtained. In this case, the radiation used may be gamma rays, ultraviolet rays, electron beams, and the like.

The radiation dose of the radiation is preferably 2 to 200 kGy, more preferably 5 to 100 kGy. If less than 2 kGy, effective cross-linking between the biocompatible polymers cannot be expected by irradiation, and in the case of 200 kGy, the flexibility of the hydrogel decreases due to the increase of the gel strength due to the increase in the amount of crosslinking, and the radiation of the polymer. Deterioration problem occurs.

In addition, the hydrogel for treating atopic dermatitis according to another embodiment of the present invention,

Dissolving the biocompatible polymer and polyhydric alcohol in distilled water or medicinal plant extract, and then casting the film into a film form (step a);

Heat treating and crosslinking the film cast in step a) (step b);

Swelling the film heat-treated in step b) with medicinal plant extracts or distilled water (step c); And

It can be prepared by a method comprising the step (step d) of crosslinking and sterilizing by irradiating the film swelled in step c) with radiation.

The step a) is a step of dissolving the above-described biocompatible polymer and polyhydric alcohol in distilled water or medicinal plant extract, and then casting it in the form of a film.

The distilled water may be preferably used tertiary distilled water, the polymer solution is cast in the form of a film.

Step b) is a step of heat-treating the film cast in step a).

Crosslinking may be introduced into the cast film through the heat treatment process. At this time, it is preferable that the thickness of the hydrogel layer is properly adjusted, and more preferably adjusted to a thickness of 1 to 5 mm. In order to ensure a stable crosslinking of the cast film, the temperature during heat treatment is preferably 80 ~ 120 ℃.

The step c) is a step of swelling the film heat-treated in step b) with medicinal plant extracts or distilled water.

When the swelling process is included, since the strength of the gel film can be improved in the form of a tape can be effectively used for atopic dermatitis symptoms in a wide area. The solvent upon swelling is selected according to the solvent used in step a). For example, if distilled water is used as the solvent in step a), medicinal plant extract is used for swelling, and distilled water is used for swelling if medicinal plant extract is used as solvent in step a).

Step d) is a step of crosslinking and sterilizing by irradiating the film swollen in the step c) with radiation.

The hydrogel is completely sterilized by the radiation and the degree of crosslinking is improved, thereby obtaining a hydrogel having excellent strength. In this case, as the radiation used, gamma rays, ultraviolet rays, electron beams, and the like may be used in the same manner as the radiation used in the method of preparing the hydrogel through freezing / thawing.

The radiation dose of the radiation is preferably 2 to 200 kGy, more preferably 5 to 100 kGy. If less than 2 kGy, effective cross-linking between the biocompatible polymers cannot be expected by irradiation, and in the case of 200 kGy, the flexibility of the hydrogel decreases due to the increase of the gel strength due to the increase in the amount of crosslinking, and the radiation of the polymer. Deterioration problem occurs.

Furthermore, the hydrogel for treating atopic dermatitis according to another embodiment of the present invention is directly irradiated by direct irradiation without undergoing freezing / thawing (step b) or primary crosslinking (step b) by heat treatment in the two manufacturing methods described above. It can be prepared by performing only crosslinking.

In this case, the radiation source and the radiation dose of the irradiated radiation can use the same source and dose as the above-mentioned manufacturing method.

The hydrogel for treating atopic dermatitis prepared by the above method inhibits the release of water, thus exhibits moisturizing action, can continuously deliver the drug, gives a cool feeling, adequately absorbs the exudates, has good gel strength, Not only can infection be prevented, but radiation can also be used to satisfy both storage and sterilization effects. In addition, animal experiments in which contact dermatitis and atopic dermatitis were induced, it was confirmed that effectively alleviate dermatitis diseases and itching. Therefore, the hydrogel according to the present invention can be effectively used for atopic dermatitis.

Hereinafter, the present invention will be described in more detail by the following examples. However, the following examples merely illustrate the present invention, and the contents of the present invention are not limited by the following examples.

< Production Example  1> Medicinal Plant Extract Preparation 1

20 g of dried vinegar, persimmon leaf, celandine, pine needles, green beans and herbs (rosemary, lavender, spearmint, chamomile or rooibos) were put in 1 L of tertiary distilled water and heated to 80 DEG C for 24 hours. Thereafter, the solid was filtered to obtain an extract.

< Production Example  2> Medicinal Plant Extract Preparation 2

20 g of the medicinal plant used in Preparation Example 1 was placed in 1 L of 70% ethanol (water: ethanol = 30: 70) and heated to 60 ° C. for 24 hours. Thereafter, the solid was filtered and the remaining liquid was removed using an evaporator under vacuum to obtain an extract.

< Production Example  3> Medicinal Plant Extract Preparation 3

An extract was obtained in the same manner as in Preparation Example 1 or 2, except that the dried medicinal plants were used instead of the dried medicinal plants.

< Production Example  4> Medicinal Plant Mixture Extract Preparation

Extracts were obtained in the same manner as in Preparation Examples 1 to 3, except that 8 g of Eoseongcho, 2 g of persimmon leaves, 8 g of celandine grass, 10 g of pine needles, 1 g of green beans, and 20 g of herbs were placed in 1 L of distilled water.

< Example  1 to 4> by freezing / thawing Polyvinyl alcohol Hydrogel  Produce

20% by weight of polyvinyl alcohol and 5% by weight of glycerin were mixed and dissolved in the medicinal plant extracts prepared according to Preparation Examples 1 to 4 at 120 ° C to cast a solution having a thickness of 1 to 3 mm. The cast formed gel was frozen at -76 ° C for 5-10 minutes, and then thawed at room temperature. The thawed gel was irradiated at 25, 35, 50 and 75 kGy doses using a Co-60 gamma ray source to crosslink and sterilize to prepare a hydrogel.

< Example  5 ~ 8> by freezing / thawing Polyvinyl alcohol Hydrogel  Manufacture 2

A hydrogel was prepared in the same manner as in Examples 1 to 4 except that an electron beam accelerator was used instead of the gamma ray source.

< Example  9 ~ 12> by freezing / thawing Polyvinyl alcohol Hydrogel  Manufacture 3

A hydrogel was prepared in the same manner as in Examples 1 to 4, except that a photoinitiator was added to the hydrogel preparation solution, and UV light was used instead of the gamma ray source.

< Example  13 ~ 16> by heat treatment Polyvinyl alcohol Hydrogel  Manufacture 1

20% by weight of polyvinyl alcohol and 5% by weight of glycerin were mixed and dissolved in the medicinal plant extracts prepared in Preparation Examples 1 to 4 at 120 ° C to cast a solution having a thickness of 1 to 3 mm. The cast film was dried and then heat treated at 120 ° C. to obtain a crosslinked film. The crosslinked film was sealed packed by swelling with distilled water at 70 ° C. The packaged films were irradiated at 25, 35, 50 and 75 kGy doses using Co-60 gamma radiation sources to crosslink and sterilize to prepare hydrogels.

< Example  17-20> By heat treatment Polyvinyl alcohol Hydrogel  Manufacture 2

A hydrogel was prepared in the same manner as in Examples 13 to 16, except that an electron beam accelerator was used instead of the gamma ray source.

< Example  21 ~ 24> by heat treatment Polyvinyl alcohol Hydrogel  Manufacture 3

The hydrogel was prepared in the same manner as in Examples 13 to 16, except that ultraviolet rays were used by using a UV-lamp (230 to 400 nm) instead of the gamma ray source after adding a photoinitiator to the hydrogel preparation solution.

< Example  25 ~ 28> by heat treatment Polyvinyl alcohol Hydrogel  Manufacture 4

20% by weight of polyvinyl alcohol and 5% by weight of glycerin were mixed, and the solution prepared by dissolving in tertiary distilled water at 120 ° C. was cast to have a thickness of 1 to 3 mm. The cast film was dried and then heat treated at 120 ° C. to obtain a crosslinked film. The crosslinked film was swollen and sealed by medicinal plant extracts prepared in Preparation Examples 1 to 4 at 70 ° C. The packaged films were irradiated at 25, 35, 50 and 75 kGy doses using Co-60 gamma radiation sources to crosslink and sterilize to prepare hydrogels.

< Example  29 ~ 32> by heat treatment Polyvinyl alcohol Hydrogel  Manufacture 5

A hydrogel was prepared in the same manner as in Examples 25 to 28 except that an electron beam accelerator was used instead of the gamma ray source.

< Example  33 ~ 36> by heat treatment Polyvinyl alcohol Hydrogel  Manufacture 6

The hydrogel was prepared in the same manner as in Examples 25 to 28, except that after the photoinitiator was added to the hydrogel preparation solution, ultraviolet rays were used instead of the gamma-ray source (230-400 nm).

< Example  37-40> Polyvinylpyrrolidone Hydrogel  Manufacture 1

7% by weight of polyvinylpyrrolidone and 3% by weight of carrageenan were mixed, and the solution prepared by dissolving at 80 ° C. in medicinal plant extracts (Preparation Examples 1 to 4) was cast to a thickness of 1 to 3 mm. The cast film was irradiated at 25, 35, 50 and 75 kGy doses using a Co-60 gamma ray source to crosslink and sterilize to prepare a hydrogel.

< Example  41-44> Polyvinylpyrrolidone Hydrogel  Manufacture 2

A hydrogel was prepared in the same manner as in Examples 37 to 40 except that an electron beam accelerator was used instead of the gamma ray source.

< Example  45-48> Polyvinylpyrrolidone Hydrogel  Manufacture 3

The hydrogel was prepared in the same manner as in Examples 37 to 40, except that ultraviolet rays were used by using a UV-lamp (230-400 nm) instead of the gamma ray source after adding a photoinitiator to the hydrogel preparation solution.

< Example  49-52> Polyacrylic acid Hydrogel  Manufacture 1

10% by weight of polyacrylic acid and 3% by weight of carrageenan were mixed and dissolved in a medicinal plant extract (Preparation Examples 1 to 4) to cast a solution having a thickness of 1 to 3 mm. The cast film was irradiated at 25, 35, 50 and 75 kGy doses using a Co-60 gamma ray source to crosslink and sterilize to prepare a hydrogel.

< Example  53-56> Polyacrylic acid Hydrogel  Manufacture 2

A hydrogel was prepared in the same manner as in Examples 49 to 52 except that an electron beam accelerator was used instead of the gamma ray source.

< Example  49-52> Polyacrylic acid Hydrogel  Manufacture 3

The hydrogel was prepared in the same manner as in Examples 49 to 52, except that UV was used by using a UV-lamp (230 to 400 nm) instead of the gamma ray source after adding a photoinitiator to the hydrogel preparation solution.

< Experimental Example  1> Contact phase  Dermatitis Reducing Effects of Animals

In order to find out the effect of the hydrogel according to the present invention on contact dermatitis was carried out the following experiment.

<1-1> Reduction effect of back edema

As shown in FIG . 1 , the hairs of C57BL / 6 mice were removed from the experimental group and the control group, and DNFB (2,4-dinitrofluorobenzenz, St. Louis, MO, USA) was diluted with acetone: olive oil = 4: 1 mixed solution. Edema was caused by applying the prepared 0.5% DNFB solution to the back of the mouse.

Thereafter, no action was taken on the control group, and the experimental group was applied to the sensitized site by applying the hydrogel prepared by Examples 1 to 12 or 37 to 48 once a day for 8 days. The state of dermatitis was observed for 8 days and the results are shown in FIG. 2 .

As shown in FIG . 2 , the control group that did not take any action showed that the edema became larger and worsened over time, whereas the sensitized area of the mouse applied with the hydrogel became smaller and recovered over time.

<1-2> ear edema of  Reduction effect

After the experiment, the hydrogel prepared by Examples 1 to 12, or 37-48, as shown in Figure 1, was pretreated by applying one days's ear once C57BL / 6 mice for four days. After 4 days, 0.2% DNFB solution was applied to the ears of the hydrogel-coated mice and the mice without the hydrogel-coated mice as a comparison group, causing ear edema. Since then over time, using the ear swelling measurements (thickness gauge, Mitutoyo Corp., Japan) as shown in Fig. 3 the ear of the test group and the control group mice measure the degree of ear swelling in accordance with the result also 4 is shown.

As shown in Figure 4 , mice without hydrogel treatment increased ear edema over time, reaching 70%, whereas mice pretreated with hydrogel according to the present invention initially had ear edema about 20%. This increase gradually reached 0, and it was confirmed that ear edema was reduced in the experimental group subjected to hydrogel pretreatment.

Therefore, the hydrogel according to the present invention can be usefully used as a dermatitis treatment agent because it reduces contact dermatitis.

< Experimental Example  2> Atopic Dermatitis Reduces Dermatitis in Animals

In order to find out the effect of the hydrogel according to the present invention on atopic dermatitis, the following experiment was performed.

 The hydrogels prepared in Examples 1-12 or 37-48 were pretreated by applying to the dorsal neck of BALB / c mice once daily for 7 days. After 7 days, 50 μg of N-methyl-p-methoxyphenethylamine and a formaldehyde polypolymer were introduced into the dermis of the skin applied with the hydrogel and the dorsal neck skin of the mouse without the hydrogel applied. compound 48/80, Sigma, St. Louis, MO, USA, hereinafter referred to as compound 48/80).

As a result, as shown in Figure 5 , it was confirmed that the rash of the skin is increased to cause atopic dermatitis. The experimental and comparative mice in which the atopic dermatitis was induced were placed in cages and photographed by observing the behavior of the mice for 60 minutes.

In order to measure the degree of itching of the skin, the mouse was observed to scratch the neck using a method proposed by the Orito group, and the number of times was counted by time, and the results are shown in FIG. 6 .

As shown in Figure 6 , the mice (comparison group) induced atopic dermatitis without pretreatment with the hydrogel prepared by Examples 1 to 12 or 37 to 48 was about 100 times the number of scratches for 30 minutes, time Although it gradually decreased, the number of scratches reached about 40 times after 60 minutes. However, mice with atopic dermatitis induced pretreatment with a hydrogel according to the present invention had a maximum number of scratches of less than 40 times, and decreased over time, so that after 60 minutes, the number of scratches approached 0, the experimental group pretreated with hydrogels. It was confirmed that the number of scratches in the decrease.

Therefore, the hydrogel according to the present invention can be useful for the prevention and treatment of atopic dermatitis because it alleviates the itching caused by atopic dermatitis.

As described above, the hydrogel according to the present invention inhibits the release of water, thereby exhibiting moisturizing effect, continuously delivering the drug, giving a cool feeling, adequately absorbing the exudates, excellent gel strength, and bacteria from bacteria. In addition to the prevention of infection, radiation storage can be used to satisfy both storage and sterilization effects. In addition, animal experiments in which contact dermatitis and atopic dermatitis were induced, it was confirmed that effectively alleviate dermatitis diseases and itching. Therefore, the hydrogel according to the present invention can be effectively used for atopic dermatitis.

Claims (19)

Dissolving the biocompatible polymer and the polyhydric alcohol in at least one extract selected from the group consisting of fish leaf, persimmon leaf, celandine, pine needles, pea beans, rosemary, lavender, spearmint, chamomile, and rooibos, and then casting (step a); Freezing and thawing the gel cast in step a) (step b); and A hydrogel for treating atopic dermatitis by radiation prepared by the method comprising the step of crosslinking and sterilizing by irradiating the hydrogel thawed in step b) with radiation (step c). According to claim 1, wherein the content of the biocompatible polymer is 1 to 50% by weight, the content of polyhydric alcohol is 1 to 20% by weight, the content of the extract is characterized in that 1 to 10% by weight Hydrogel for the treatment of atopic dermatitis. According to claim 1, wherein the biocompatible polymer is at least one synthetic polymer selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone polyacrylic acid and polyethylene oxide, or sodium carboxymethyl cellulose, gelatin, agar, alginate and For treatment of atopic dermatitis by irradiation, characterized in that the mixture of at least one natural polymer selected from the group consisting of chitosan or at least one polymer selected from the synthetic polymer group and at least one polymer selected from the natural polymer group. Hydrogel. The hydrogel of claim 1, wherein the biocompatible polymer is polyvinyl alcohol alone or a mixture of polyvinylpyrrolidone or polyacrylic acid and carrageenan. According to claim 4, wherein the content of the polyvinyl alcohol is 1 to 50% by weight, the content of polyvinylpyrrolidone is 1 to 30% by weight, the content of polyacrylic acid is 1 to 20% by weight, the content of carrageenan A hydrogel for treating atopic dermatitis by radiation, characterized in that 1 to 5% by weight. The polyhydric alcohol of claim 1, wherein the polyhydric alcohol is selected from the group consisting of glycerin, ethylene glycol, propylene glycol, 1-3-butylene glycol, hexylene glycol, sorbitol, mannitol, or polyethylene glycol. Hydrogel for treating atopic dermatitis by irradiation with radiation, characterized in that a mixture of alcohols. delete delete According to claim 1, wherein the extract is 5 to 25% by weight Eoseongcho, 5 to 25% by weight persimmon leaf, 5 to 25% by weight of celandine grass, 5 to 25% by weight pine needles, 5 to 10% by weight green beans and rosemary, lavender, spearmint , Chamomile, rooibos any one or more selected from the group consisting of 5 to 30% by weight of hydrogel for treatment of atopic dermatitis by irradiation. delete According to claim 1, wherein the freezing temperature used in step b) is -100 ~ -15 ℃, thawing temperature is 5 ~ 50 ℃ hydrogel for treating atopic dermatitis by irradiation, characterized in that. The hydrogel of claim 11, wherein the freezing temperature is -70 ~ -40 ℃, the thawing temperature is 20 ~ 30 ℃. Dissolving the biocompatible polymer and polyhydric alcohol in one or more extracts selected from the group consisting of distilled water or horseweed, persimmon leaf, celandine, pine needles, green beans, rosemary, lavender, spearmint, chamomile, and rooibos, and then casting them into a film form ( Step a); Heat treating and crosslinking the film cast in step a) (step b); Swelling the film heat-treated in step b) with one or more extracts or distilled water selected from the group consisting of eochocho, persimmon leaves, celandine, pine needles, peas, rosemary, lavender, spearmint, chamomile, and rooibos (step c); And A hydrogel for treating atopic dermatitis by radiation produced by the method comprising the step of crosslinking and sterilizing by irradiating the film swelled in step c) with radiation (step d). The hydrogel for treating atopic dermatitis by irradiation with radiation according to claim 13, wherein the heat treatment temperature of step b) is 80 to 120 ° C. The hydrogel for treating atopic dermatitis by radiation according to claim 1 or 13, which is prepared by performing crosslinking only by irradiation without performing crosslinking by freezing / thawing or heat treatment. The radiation according to any one of claims 1 to 6, 9 and 11 to 14, wherein the radiation to be irradiated is any one selected from the group consisting of gamma rays, ultraviolet rays and electron beams. Hydrogel for the treatment of atopic dermatitis by irradiation. The hydrogel for treating atopic dermatitis according to claim 16, wherein the radiation dose is 2 to 200 kGy. The hydrogel of claim 15, wherein the irradiated radiation is any one selected from the group consisting of gamma rays, ultraviolet rays, and electron beams. 19. The hydrogel for treating atopic dermatitis by radiation according to claim 18, wherein the radiation dose is 2 to 200 kGy.

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