KR20170139962A - Hydrogel patch containing peptides regulating neurotransmitter for benefit ingredient - Google Patents

Abstract

The present invention provides a hydrogel patch containing a skin cosmetic bioactive peptide. The hydrogel patch can improve skin permeation efficiency of substances capable of controlling release of a neurotransmitter having a wrinkle reducing effect.

Description

[0001] The present invention relates to a hydrogel patch containing a peptide for regulating a neurotransmitter as a useful ingredient,

The present invention relates to a hydrogel patch, and more particularly, to a hydrogel patch having a skin wrinkle improving effect.

Hydrogels using gelation of water-soluble polymeric materials have been studied as drug delivery systems for the efficient delivery of cosmetic and pharmaceutical ingredients. In particular, hydrogels are molecularly insoluble in a three-dimensional network structure, and have a property of absorbing and discharging a large amount of water. Therefore, it has been utilized for the purpose of cosmetic and cosmetic based on the transdermal delivery system containing a functional substance.

In particular, in the case of hydrogel masks used for cosmetic purposes, it is a skin care system designed to continuously and effectively deliver the efficacy and effects by storing effective cosmetic ingredients inside a water-soluble polymer structure constituting a hydrogel.

In order to utilize it as a useful ingredient, various skin delivery drugs have been developed for improvement of skin diseases and skin moisturizing effect, and studies using peptides have been actively carried out.

Delivery of the drug through the skin has been used in a variety of fields and forms due to its ease of use. Drugs that pass through the skin are mainly intended to be delivered to the systemic circulation through the skin. In addition, medicines such as an atopy treatment agent, a whitening agent, or a cosmetic agent for improving wrinkles may be used for the purpose of delivering the drug to the skin's own organs . Despite this convenience and functionality, there are many limitations in delivering a drug through the skin in the structure of the skin, and it is necessary to increase the amount of drug passing through the skin. The stratum corneum of the skin is composed of a brick structure composed of keratin-rich keratinocytes and a lipid-filled mortar such as ceramide, fatty acid, or wax. Structure. This structure acts as a barrier and has very low permeability to materials. In general, only low molecular weight components of 500 Da or less can be delivered into the skin by the diffusion method, and only substances having excellent lipid affinity can easily pass through the skin.

On the other hand, the release of neurotransmitters is caused by the formation of a passage between the two boundaries after fusion of the synaptic vesicle and the presynaptic membrane located at the nerve endings containing the neurotransmitter. The SNARE protein, a three-protein complex consisting of the vaprotein VAMP (synaptobrevin) and the plasma membrane-binding proteins Syntaxin 1a and SNAP-25, provides a fundamental force for the fusion of synaptic vesicles and synaptic membrane. Here, the neurotransmitter release pathway is opened by membrane fusion between the synaptic vesicle and the synaptic membrane. The synaptic 1a protein attached to the target membrane and the t-SNARE and vesicle (complex of two SNAP-25 proteins) vesicle) of the v-SNARE. During the membrane fusion, rearrangement of the lipid bilayer occurs. Since the biomembranes push strongly against each other, these membranes are supposed to overcome the repulsion between the membranes by giving them strong force from the outside without being spontaneously fused. It is known that SNARE protein provides this force. Thus, the formation of the SNARE complex is a key phenomenon of exocytosis involving the release of neurotransmitters.

In recent years, there has been development of a peptide having a similar role to Botox, which reduces muscle contraction without toxic side effects in a non-invasive manner. These peptides temporarily block the secretion of neurotransmitters such as acetylcholine, which is responsible for the contraction of muscle cells, and play a role in relieving wrinkles. However, in spite of the development of a peptide having a role similar to that of Botox, there is a problem in that the effect is insufficient when applied to skin as a formulation such as cream, and the original efficacy can not be exhibited.

Thus, the present inventors have utilized the hydrogel system to contain the wrinkle-improving peptide, thereby promoting the delivery of the skin and enhancing the effect.

A problem to be solved by the present invention is to provide a method for controlling the release of neurotransmitters to exert the efficacy of a peptide having a wrinkle-reducing effect.

The present invention provides a hydrogel patch capable of increasing the efficiency of delivering a substance having a skin wrinkle reducing effect into the skin by regulating the release of a neurotransmitter.

An embodiment of the present invention provides a hydrogel patch containing a skin cosmetic bioactive peptide.

More preferably, the hydrogel patch enhances the wrinkle-reducing effect by improving the delivery of the skin-care bioactive peptide, which is a useful ingredient.

More specifically, in general, a peptide used in cosmetics is an oligopeptide composed of 2 to 10 amino acids and has a molecular weight ranging from about 200 to about 1500 Da. In general, the molecular weight of the skin absorbable in the natural state is less than 500 Da, and thus, when the oligopeptide is applied in a conventional formulation, the permeation amount of the peptide having a molecular weight of 500 Da or more is significantly reduced. In particular, in the case of peptides for achieving the effect of inhibiting muscle contraction at the neuromuscular junction, it was necessary to search for a method for effectively delivering the active ingredient to the muscle region.

The inventors of the present invention found that when a skin cosmetic physiologically active peptide, particularly an oligopeptide of 500 Da or more, is delivered using a hydrogel patch, the fluidity of the skin is increased through continuous water supply, And the present invention has been completed.

The skin-beauty biologically active peptide refers to a peptide used in the cosmetics, cosmetics, and pharmaceutical fields in order to obtain a skin condition-improving effect, and peptides having an anti-wrinkle effect are most typical.

In one embodiment of the present invention, the skin-aqua physiologically active peptide contained in the hydrogel patch comprises i) a peptide which plays a role of increasing or changing collagen synthesis and inhibiting collagen degradation by collagenase, ii) A peptide that inhibits muscle contraction at the neuromuscular junction and exhibits an effect like a botox, iii) a peptide that transports a metal such as copper, and may include peptides that move the cofactor essential for dermatological construction to the dermis.

Thr-Thr-Lys-Ser (KTTKS), Val-Gly (KTTKS), and the like, which function to increase or alter collagen synthesis and inhibit collagen degradation by collagenase, Lys-Thr-Thr-Lys-Ser (pal-KTTKS), Tyr-TyrArg-Ala-Asp-Asp-Arg (YYRADDR) and the like.

ii) Peptides that inhibit muscle contraction at neuromuscular junctions and exhibit botox-like effects can regulate neurotransmitter release and have wrinkle-reducing effects. For ^{example, Acetyl hexapeptide (ARGIRELINE ®),} Infinitec社of X50 Myocept ^TM, (Pal) -Tyr-Pro-Trp-The-Gln-Arg ([Pal] DdPQRR), Palmitoyl-hexapeptide-52 -Phe ([Pal] YPWTQRF), Argireline (TM), Acetyl-EEMQRR), GABA (gamma-amino butyric acid), botulinum toxin, ≪ / RTI >

Also included are peptides having the formula 1, isomers thereof, racemic compounds, their cosmetic or pharmaceutically acceptable salts, and the like.

[Chemical Formula 1]

R ₁ -AA-R ₂

Wherein AA can be an amino acid sequence comprising 3-40 amino acids, and R ₁ can be any _one of H or C ₃ to C ₂₄ alkyl, aryl, or acyl groups;

R ₁ of the peptide of formula 1 may be an acyl group having 3 to 24 carbon atoms and the acyl group may be saturated or unsaturated and may be linear, branched or cyclic ).

More preferably, R ₁ is an acyl group of the formula CH ₃ - (CH ₂ ) _m -CO-, and m may be any one selected from 1 to 22.

More preferably, R < ₁ > may be a polyethylene glycol polymer having a molecular weight of 200 to 35,000 Da.

Preferably the AA is MAEDADMRNELEEMQRRADQL, ADESLESTRRMLQLVEESKDAGI, ELEEMQRRADQLA, ELEEMQRRADQL, ELEEMQRRADQ, ELEEMQRRAD, ELEEMQRRA, ELEEMQRR, LEEMQRRADQL, LEEMQRRADQ, LEEMQRRAD, LEEMQRRA, LEEMQRR, EEMQRRADQL, EEMQRRADQ, EEMQRRAD, EEMQRRA, EEMQRR, LESTRRMLQLVEE, NKDMKEAEKNLT, KNLTDL, IMEKADSNKTRIDEANQRATKMLGSG, SNKTRIDEANQRATKMLGSG , TRIDEANQRATKMLGSG, DEANQRATKMLGSG, NQRATKMLGSG and QRATKMLGSG.

Wherein R ₂ of the peptide of Formula 1 is a C ₁ to C ₂₄ aliphatic or cyclic group and the C ₁ to C ₂₄ aliphatic or cyclic group is unsubstituted or substituted with one or more substituents selected from the group consisting of An amino group, a hydroxyl group or a thiol group.

The AA may also include an amino acid sequence derived from the amino and carboxy domain of SNAP-25 protein.

For example, the substituents of R 1 and R 2 in the above formula (1) may be those known from US 2010-0021510 A1, and the entire contents of US 2010-0021510 A1 are incorporated herein. The compounds of the above formula (1) can be used in the examples disclosed in US 2010-0021510 A1.

iii) Peptides that move the cofactor to the dermis, essential for dermis construction, include the tripeptide GHK and may also contain GHK-Cu.

A preferred embodiment of the present invention may include acetyl hexapeptide-8 as a skin cosmetic bioactive peptide.

The hydrogel patch according to an embodiment of the present invention may include a natural polymer for the purpose of gel formation, intensity control, control of a false-positive image, and improvement in feeling. Specific examples thereof include konjac, Carrageenan, Gellan gum ), Locust bean gum (LBG), gelatin, agar, alginate, acacia gum, gum arabic, starch, Pullulan, galactomannan, guar gum, One or more selected from the group consisting of Pluronic, Algin, xanthan gum, pectin and cellulose can be used in combination. Preferably, locust bean gum, carrageenan or a mixture thereof can be used, and most preferably, locust bean gum and carrageenan can be used together.

When the locust-type gelled polymer, locust bean gum, and carrageenan, which is an electrolytic gelling polymer, are used together, the skin-transmitting physiologically active peptide of the present invention is excellent in skin transplantation efficiency and excellent skin wrinkle-reducing effect can be obtained. In addition, it is possible to actively adsorb (absorb) and discharge a large amount of solvent (water-soluble substances including water), that is, water release can be actively performed, and skin adhesion of skin cosmetic bioactive peptide Can be improved.

The hydrogel patch according to an embodiment of the present invention may further include a moisturizing agent, a pH adjusting agent, a sequestering agent, and the like.

The humectant may be at least one selected from the group consisting of glycerin, dipropylene glycol, propylene glycol, butyleneglycol, phage-60 hydrogenated castor oil, betaine and squalane, preferably glycerin Can be used.

The components used as the moisturizing agent can reduce the dissolution time of the gel-forming polymer for producing the hydrogel patch of the present invention. In particular, the carrageenan and the locust bean gum can be dissolved without aggregation when they are dissolved in water.

The hydrogel patch of the present invention may further include components used in the manufacture of cosmetics. For example, the hydrogel patch of the present invention can be applied to gelatin, casein, albumin, hyaluronate, starch, gum arabic, locust bean gum, Cellulose, hydroxyethyl cellulose, cellulose acetate, stearyl cellulose, phosphorylated starch, cyanoethylated starch, carboxymethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose, carboxymethylcellulose, Hydroxyethylated starch, polyacrylic acid, polymethylacrylic acid, polystyrene sulfonic acid, styrene-malic anhydride copolymer, polyethyleneimine, polyvinylpyridine, polydiethylaminoethylacrylic acid, polyvinyl alcohol, polyacrylamide , Alkyd, polyvinylpyrrolidone, polyethylene glycol, and Polyethylene glycol, polyethylene glycol, and polyethylene polyvinyl methyl ether.

The hydrogel patch of the present invention may contain 0.1 to 10% by weight of the skin care physiologically active peptide relative to the total weight of the hydrogel patch, and can provide excellent skin wrinkle improving effect and skin contact feeling of the patch in the above content range.

The hydrogel patch according to another embodiment of the present invention comprises acetyl hexapeptide-8, carrageenan gum and locust bean gum as a gelling polymer, and the weight ratio of the acetylhexapeptide to the gelled polymer is acetylhexapeptide: gelling polymer 0.01 to 10: 1 by weight.

Further, the present invention provides a hydrogel patch system comprising the above-mentioned peptide as a useful component.

As used herein, the term "patch" refers to an adhesive agent containing an active ingredient, meaning any form of preparation (or drug delivery system) that is used by attaching the active ingredient to the site necessary for penetration through the skin into the body Respectively. The shape of the patch is not particularly limited, but preferably the patch of the present invention may be provided in the form of a mask, a sheet type pack, or the like. More preferably in the form for adhering to the face, especially in the skin.

The hydrogel patch of the present invention can be produced by a method for producing a conventional hydrogel patch in the industry, and the production method is not particularly limited.

The present invention also provides a skin absorption method using a hydrogel patch according to the present invention, wherein the skin permeation efficiency of a peptide is improved, and a neurotransmitter release controlling substance skin absorption method.

In addition, the present invention provides a wrinkle-improving use of a hydrogel patch containing a substance having a wrinkle-reducing effect by controlling the release of the neurotransmitter.

The present invention provides a hydrogel patch for improving skin wrinkles containing a skin cosmetic biologically active peptide.

In one embodiment, the hydrogel patch comprises carrageenan gum and locust bean gum as gelling polymer, and acetyl hexapeptide-8 is contained in an amount of 0.1 to 10 wt% based on the total weight of the hydrogel patch. Gel patches.

The present invention provides a hydrogel patch comprising a skin cosmetic biologically active peptide, particularly a peptide having a skin wrinkle-improving effect, as a useful component.

The present invention provides a hydrogel patch capable of improving the skin permeation efficiency of substances capable of controlling release of a neurotransmitter having a wrinkle-reducing effect.

The present invention also provides a skin permeation method of a peptide, which uses such a hydrogel patch.

BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate preferred embodiments of the invention and are incorporated in and constitute a part of this specification, do.
1 is a hydrogel mask prepared according to the present invention.
2 shows a Franz diffusion cell for evaluating drug release behavior of a micro needle according to the present invention.
FIG. 3 is a graph showing the skin permeation amount of a peptide measured using a peptide hydrogel mask of the present invention and a Franz diffusion cell of a peptide cream.
FIG. 4 shows the effect of the peptide hydrogel mask and the peptide cream of the present invention on skin wrinkles.

Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

≪ Preparation of hydrogel >

For the preparation of the hydrogel, the solution was uniformly mixed and stirred at 80 for about 10 minutes. The hydrogels without peptides had the composition of Example 1 of Table 1 and the hydrogels containing the peptides were prepared with the composition of Example 2 of Table 1. The homogeneously prepared solution was thinly and uniformly applied on the release-treated plipropylene film to a thickness of 1 mm using a doctor blade. Thereafter, it was cut into a certain size and put in an aluminum pouch for cosmetics so that moisture was not evaporated, and then packed and stored with a heat-sealer.

ingredient Example 1 Example 2 Carrageenan One One Locust bean sword One One glycerin 8 8 Acetyl hexapeptide-8 - One water 90 89 Total amount 100 (%) 100 (%)

≪ Preparation of an emulsion type cream containing peptide impregnated >

In order to compare the skin permeation amount of the peptide impregnated in the hydrogel, the peptide was impregnated with a general oil-in-water (O / W) cream as a comparative example and compared.

ingredient Formulation Example C14-22 alcohol, C12-20 alkyl glucoside
(Mixture C14-22 alcohol: C12-20 alkyl glucoside = 80: 20 weight ratio) 1.5 Glyceryl stearate, phage-100 stearate
(Mixture 50:50 weight ratio) 1.2 Glyceryl stearate 0.9 Cetearyl alcohol 1.5 Polyglyceryl-3 methyl glucoside distearate 1.5 Hydrogenated polydecene 4.5 Cyclohexasiloxane 3.5 Carbomer 0.2 Tromethamine 0.2 glycerin 3.0 Dipropylene glycol 5.0 1,2-hexanediol 2.0 Acetyl hexapeptide-8 1.0 Purified water Remaining amount (To 100)

<Drug Release Behavior>

Peptide (Acetyl hexapeptide-8) release from the hydrogel mask prepared above was evaluated using a Franz diffusion cell equipped with pig skin (Fig. 2). As an acceptor solution, a PBS solution containing 30% by weight of DPG was used.

In other words, using Franz diffusion cell, peptide content of pig skin tissue and acceptor solution with time was measured by Liquid Chromatography.

The amount of peptides contained in the cream was about 0.1 ㎍ in the amount of permeation through the skin, but the amount of the peptide impregnated in the hydrogel was directly transmitted to the skin due to skin expansion and sealing effect, and its permeation amount was 10 μg or more The skin permeability was 100 times higher than that of cream.

These results are shown in Fig.

&Lt; Wrinkle improvement effect &

The peptide cream was treated daily for 4 weeks on the wrinkles of the eyes and the hydrogel mask impregnated with the peptides was treated on the entire face for 4 weeks and once every 2 days to measure the degree of wrinkle improvement on the silicone replica and wrinkle image analysis Respectively. (N = 20)

It was found that the hydrolytic gel of the present invention showed an improvement of more than three times in the hydrogel mask impregnated with the peptide as compared with the peptide cream. This confirmed that the ppt tide effectively penetrated into the skin by the hydrogel mask and the wrinkle improving effect was high. These results are shown in Fig.

Claims (9)

A hydrogel patch containing a skin cosmetic bioactive peptide. The hydrogel patch according to claim 1, wherein the skin cosmetic bioactive peptide is a peptide which modulates neurotransmitter release and has a wrinkle-improving effect. The hydrogel patch according to claim 1, wherein the skin cosmetic bioactive peptide is acetyl hexapeptide-8. The method of claim 1, wherein the hydrogel patch is selected from the group consisting of purified water, glycerin, dipropylene glycol, propylene glycol, butyleneglycol, Piggy-60 hydrogenated castor oil, dipotassium glycyrrhetate, Wherein the hydrogel patch further comprises at least one selected from the group consisting of polymers. The method of claim 4, wherein the gel-forming polymer is selected from the group consisting of gelatin, casein, albumin, hyaluronate, starch, gum arabic, locust bean gum, xanthan gum, tragacanth, capectin, alginic acid, carrageenan, agar, carboxymethylcellulose, Hydroxyethylated starch, polyacrylic acid, polymethylacrylic acid, polystyrenesulfonic acid, styrene, hydroxypropylmethylcellulose, ethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, stearylcellulose, phosphorylated starch, cyanoethylated starch, carboxymethyl starch, hydroxyethylated starch, Polyvinylpyrrolidone, polyvinylpyrrolidone, polyethylene glycol, and polyvinylpyrrolidone copolymers such as polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, Any one or more selected from the group The hydrogel patch of claim. The hydrogel patch according to claim 1, wherein the hydrogel patch comprises 0.1 to 10% by weight of the skin care physiologically active peptide based on the total weight of the hydrogel patch. The method of claim 1, wherein the hydrogel mask comprises acetylhexapeptide-8,
Carrageenan gum and locust bean gum as gelling polymers,
Wherein the weight ratio of the acetylhexapeptide-8 to the gelled polymer is in the range of 0.01 to 10: 1 by weight of acetylhexapeptide: gelled polymer. A hydrogel patch for improving skin wrinkles containing a skin cosmetic bioactive peptide. The method according to claim 1,
The hydrogel patch comprises carrageenan gum and locust bean gum as a gelled polymer,
Acetyl hexapeptide-8 in an amount of 0.1 to 10% by weight based on the total weight of the hydrogel patch.
A hydrogel patch for improving skin wrinkles.

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