WO2016167545A1

WO2016167545A1 - Soluble microneedle containing ingredient for controlling release of neurotransmitters

Info

Publication number: WO2016167545A1
Application number: PCT/KR2016/003845
Authority: WO
Inventors: 강내규; 이현종; 장윤희; 김태윤; 김기영; 심우선
Original assignee: 주식회사 엘지생활건강
Priority date: 2015-04-13
Filing date: 2016-04-12
Publication date: 2016-10-20

Abstract

The present invention relates to a skin administration system capable of improving the efficiency of skin delivery of an ingredient for controlling release of neurotransmitters and, particularly, to a microneedle containing an ingredient for controlling release of neurotransmitters.

Description

Soluble microneedle with ingredients that regulate the release of neurotransmitters

This application is filed in Korean Patent Application No. 10-2015-0052043, filed April 13, 2015, Korean Patent Application No. 10-2015-0159978, filed April 13, 2015, and April 14, 2015. Claims priority based on Korean Patent Application No. 10-2015-0052575, and Korean Patent Application No. 10-2015-0144855, filed October 16, 2015, and all other contents disclosed in the specification and drawings of that application. Is incorporated in this application.

FIELD OF THE INVENTION The present invention relates to soluble microneedles and relates to skin administration systems capable of delivering to the skin a substance that controls the release of neurotransmitters.

Delivering drugs through the skin has been used in a variety of fields and forms because of their ease of use. Drugs that pass through the skin are mainly intended for delivery through the skin to the systemic circulation, but in addition to drugs such as atopy treatments, whitening or anti-wrinkle cosmetics may be used for the purpose of delivery to the organs of the skin itself. . Despite these conveniences and functionalities, there are many difficulties in delivering drugs through the skin due to the structure of the skin, and it is not easy to develop drugs that cross the skin. The stratum corneum of the skin is a brick structure consisting of keratin-rich keratinocytes, and a mortar filled with lipids such as ceramide, fatty acids, or waxes between the keratinocytes. It consists of a structure. This structure acts as a barrier and has a very low material permeability. Only low molecular structure components of 500 Da or less can be delivered into the skin by diffusion, and only substances with good lipid affinity can pass through the skin.

On the other hand, the release of neurotransmitters is caused by the formation of a pathway between the two boundaries after the synaptic vesicle and the presynaptic membrane are fused at the nerve terminal containing the neurotransmitter. SNARE proteins, a protein complex consisting of the vesicle protein VAMP (synaptobrevin) and the plasma membrane binding proteins Syntaxin 1a and SNAP-25, provide a fundamental force for the fusion of synaptic vesicles with the entire synaptic membrane. . Herein, the neurotransmitter excretion pathway is opened by membrane fusion between synaptic vesicles and the synaptic epithelium, t-SNARE and vesicles (a complex of syntaxin 1a protein and SNAP-25 protein attached to the target membrane). This is the result of the operation of v-SNARE attached to the vesicle. When the membrane is fused, rearrangement of the lipid bilayer occurs. Since the biofilms push strongly against each other, these membranes are not spontaneously fused and have a strong force from outside to overcome the repulsion between the membranes, which is known to provide SNARE protein. As such, the formation of the SNARE complex is a key phenomenon of extracellular exocytosis, including the release of neurotransmitters.

Recently, efforts have been made to apply cosmetics or botox in a situation in which it is not possible to use botox by using the plant polyphenols, which control the neurotransmitter and exhibit similar effects to botox. Due to poor solubility, the amount that can be contained in the cosmetic formulation is limited, and thus there is a problem in that the amount of skin permeation is very low and the efficacy is difficult to be exhibited.

On the other hand, calcium channel blocker (Calcium channel blocker) is known to reduce the contraction of the muscle by acting to inhibit the calcium, which is an important factor for contracting the muscle to enter the muscle vascular fiber cells. Facial movements are caused by the contraction of muscles under the skin, allowing different muscles to move different parts of the face.

In order to reduce the muscle contraction and to relax the muscles, the calcium channel blocker had to be delivered to the muscle layer, so that the simple application of cosmetics had difficulty in absorbing the drug to the muscle layer.

Injecting calcium channel blockers into the skin can be limited to use by individuals because they involve pain and require treatment, and side effects can occur because oral administration affects the whole body.

There are attempts to deliver calcium channel blockers to cosmetics to improve wrinkles and lines to the skin, but there are no considerations for improving skin permeation.

Therefore, the problem to be solved by the present invention is to provide a soluble microneedle excellent skin penetration amount.

It impregnates soluble microneedle with components that have excellent wrinkle improvement by blocking neurotransmission and are applied to skin without pain by microneedle and applied to skin, while microneedles are dissolved by moisture in skin and deliver drugs into skin. To provide a soluble microneedle.

The present invention allows the effective needle to be delivered into the skin while the fine needle is dissolved by the water in the skin.

The present invention aims to reduce the release of neurotransmitter by the active ingredient delivered into the skin to relax the muscles to improve wrinkles and facial lines and to suppress pain.

The present invention is to solve the problem that the solubility is not good in the general cosmetic composition limited the amount of polyphenols used, improve the solubility of polyphenols to provide a skin delivery system that can be applied to the skin.

In order to solve the above problems, the present invention provides a microneedle comprising a component for controlling the release of neurotransmitter, preferably the microneedle is a soluble microneedle.

The component that modulates the release of neurotransmitters may be i) polyphenols or derivatives thereof, ii) calcium channel blockers, or iii) mixtures thereof.

According to one embodiment of the invention, the microneedle preferably contains the microneedle containing a component for controlling the release of neurotransmitter, and has a wrinkle improvement effect. The material forming the microneedles may be dissolved or biodegradable in the skin, and the microneedles are dissolved or decayed when the microneedles are applied to the skin, thereby releasing components that control the release of the neurotransmitter, and the release of the neurotransmitter. Ingredients that regulate the ability to be delivered to the skin stably.

According to an embodiment of the present invention, the components included in the microneedle include polyphenols or derivatives thereof.

The present inventors have studied a variety of administration systems, and as mentioned above, any system has a low solubility, and thus the application of the polyphenol to the general cosmetics is limited only by application to the skin. The inventors have made a surprising invention that, after various efforts, by containing polyphenols in the soluble microneedle in the skin, it can effectively reduce the transmission of neurotransmitters to exhibit wrinkle improvement.

To achieve this task, microneedles must be soluble in the skin, and hyaluronic acid, sodium carboxymethyl cellulose (Na-CMC, Sodium carboxymethyl cellulose) and vinyl blood to form soluble microneedles. Water-soluble polymers such as a rollidone-vinylacetate copolymer, poly vinyl alcohol, and poly vinyl pyrrolidone; Sugars such as xylose, sucrose, maltose, lactose, trehalose and the like; Or mixtures thereof may be used. In particular, considering the skin penetration intensity of microneedles and the dissolution rate in the skin, hyaluronic acid, sodium carboxymethyl cellulose (Na-CMC), and sugars (More preferably, a mixture of trehalose) is further preferred, and even more preferably mixed up to glycerin, which will be described later. Preferably, the microneedle according to the present invention may further include a plasticizer, a surfactant, a preservative, an anti-inflammatory agent and the like in addition to the above-mentioned components forming the microneedle.

As the plasticizer, for example, polyols such as ethylene glycol, propylene glycol, dipropylene glycol, dipropylene glycol, butylene glycol, glycerin, etc. may be used alone. Or may be used in admixture.

Preferably, the microneedle of the present invention controls the neurotransmitter discharge, and may contain 0.01 to 10% by weight, more preferably 0.1 to 5% by weight of polyphenol having a wrinkle improvement effect relative to the total weight of the microneedle. have.

The microneedle may comprise a high content of polyphenol components and may provide a polyphenol skin delivery system in which the amount delivered to the skin is significantly increased compared to formulations of common cosmetic compositions.

The polyphenol component was poorly soluble, so that the amount contained in the cosmetic composition was extremely low, but the microneedle of the present invention was extremely low in water so that it could be delivered to the skin by applying a high content to the microroll needle without precipitation of the polyphenol component.

The polyphenols are camphorol, quercetin, myricetin, luteolin, delchinidine, cyanidin, butane, ellagic acid, ampelopsin, hesperydine, aurantinidin, europinidin, pella May be at least one selected from the group consisting of Peargonidin, Malvidin, Peonidin, Peunidin, Petunidin, and Rossinidin, and derivatives thereof. May be any one or more selected from the group consisting of ampelopsin, hesperidin or derivatives thereof.

Derivatives of the polyphenols herein are free form (free acid or base form) and all prodrugs, polymorphs, hydrates, solvates, tautomers, steric Unless otherwise specified, isomers include all pharmaceutically acceptable forms as described above and are used in the sense to include all active forms of the compounds. In accordance with an embodiment of the present invention, the microneedle containing polyphenols inhibits the formation of SNARE complexes and inhibits membrane fusion. As a result, the microneedles inhibit the release of neurotransmitters such as acetylcholine. Shrinkage can be suppressed.

In addition, the present invention provides a microneedle patch system for administration (delivery) of polyphenols or derivatives thereof to which the microneedle is attached.

The microneedles of the present invention can be prepared by a method of manufacturing conventional soluble microneedles in the art, and the production method is not particularly limited.

For example, the microneedle manufacturing method of the present invention (S1) is a solution containing a component (for example, calcium channel blocker, polyphenol or derivatives thereof, or mixtures thereof) to control the release of neurotransmitters. Manufacturing step; (S2) injecting the solution into the microneedle mold; And (S3) drying and separating the microneedle from the mold.

The present invention also provides a method for administering the skin of polyphenols having improved solubility and improved skin delivery, characterized by using the microneedle according to the present invention.

In another aspect, the present invention provides a wrinkle improvement use of the microneedle containing the polyphenol having the effect of improving the wrinkles, and control the neurotransmitter discharge.

According to one embodiment of the present invention, the present invention provides microneedles containing polyphenols and inhibiting SNARE complex formation.

According to another embodiment of the present invention the present invention provides a skin wrinkle improvement of the microneedle containing a component for controlling the release of neurotransmitter.

According to yet another embodiment, the present invention provides a microneedle containing a calcium channel blocker, and has an effect of improving wrinkles or improving facial contour through muscle relaxation. More preferably, the material forming the microneedle is dissolved in the skin to release or disintegrate the calcium channel blocker upon application of the microneedle to the skin, and the calcium channel blocker can be stably delivered to the skin.

The inventors have studied a variety of dosage systems and have, after many efforts, contained calcium channel blockers in soluble microneedles in the skin, effectively reducing the delivery of neurotransmitters, inhibiting muscle contraction, and improving skin wrinkles or facial The contours have been improved to create an amazing invention that can produce lifting effects.

When applied to the cosmetic formulations such as creams, lotions, etc. containing a calcium channel blocker, the poor skin penetration effect was not achieved properly, when using the injection there was a disadvantage that can not be applied to individuals at home. The present inventors have completed the present invention as a result of finding a way to easily improve the skin wrinkles without pain while solving these problems.

Preferably, the microneedle of the present invention contains 0.0001 to 20% by weight of calcium channel blocker to the total weight of the microneedle preparation solution, and more preferably 0.001 to control the release of neurotransmitter and control skin muscle contraction. To 5% by weight.

As used herein, a "calcium channel blocker" is also referred to as a calcium antagonist and refers to a substance that blocks calcium from entering the muscle and thereby inhibits muscle contraction. The calcium channel blocker is at least one member of the group consisting of copper gluconate, zinc gluconate, magnesium sulfate, magnesium gluconate and magnesium aspatate. Organometallic compounds selected; At least one dihydropyridine calcium channel blocker selected from the group consisting of amlodipine, lercanidipine, felodipine, nifedipine, nicardipine, isradinine, nisoldipine and pharmaceutically acceptable salts thereof; Phenylalkylamine based calcium channel blockers including verapamil; Benzothiapine-based calcium channel blockers including dithiazem; And N-type calcium channel blockers selected from the group consisting of gabapentinoids and zinconotides; It may be any one or more selected from the group consisting of, any material capable of muscle relaxation by blocking calcium flowing into the calcium channel may be included, and the type is not particularly limited.

The calcium channel blocker may preferably use magnesium gluconate.

In addition, the present invention provides a microneedle patch system, preferably a microneedle patch system for calcium channel blocker administration (for delivery), comprising a component for controlling the release of neurotransmitters to which the microneedle is attached. .

The present invention also provides a method of skin administration of a component for controlling the release of neurotransmitters with improved skin delivery rate, preferably a method of skin administration of a calcium channel blocker, characterized in using the microneedle according to the invention.

In another aspect, the present invention provides a microneedle for facial muscle relaxation and its facial muscle relaxation uses, including a microneedle containing a component for controlling the discharge of the neurotransmitter.

The facial muscle relaxation is a concept including the use of improving the wrinkles by inhibiting the muscle contraction of the skin, the use of improving the contour of the face, the use of having a lifting effect by preventing the sagging of the skin.

According to an embodiment of the present invention, there is provided a method of skin administration of a component for controlling the release of neurotransmitters using the microneedle of the present invention, preferably a method of skin administration of a calcium channel blocker for wrinkle improvement.

The present invention provides a microneedle having a skin wrinkle improvement effect.

The present invention provides a microneedle for skin administration, which can improve the skin permeation efficiency of the polyphenol having a wrinkle improvement effect. The present invention also provides a method for administering the skin of a component that modulates the release of neurotransmitter, characterized by using such microneedles.

The present invention provides a microneedle having a skin wrinkle improvement effect or facial contour line improvement effect.

The present invention can transmit the active ingredient into the skin without pain by the microneedle.

The present invention can inhibit the calcium channel of nerve cells to block the release of neurotransmitters to relax the muscles to improve wrinkles and facial lines.

The following drawings, which are attached to this specification, illustrate preferred embodiments of the present invention, and together with the contents of the present invention serve to further understand the technical spirit of the present invention, the present invention is limited to the matters described in such drawings. It should not be construed as limited.

1 is a view showing an example of several methods for manufacturing a microneedle according to the present invention. The soluble microneedle may be prepared by a solution casting method, and the solution may be cast into a mold to fill a fine mold with a vacuum and / or centrifuge, followed by drying. As the material forming the microneedle structure, general synthetic and natural water-soluble polymers may be used.

Figure 2 shows a Franz diffusion cell for evaluating the drug release behavior of the microneedle according to the present invention.

3 exemplarily shows a polyphenol having a Botox-like effect of the present invention. Myricetin, delchinidine, cyanidin, camphorol, quercetin, pisetin, butane, luteolin, ellagic acid, EGCG (Epigallocatechin gallate), ampfellopsin, hesperidin and derivatives thereof can be used.

Figure 4 shows the results confirmed the inhibition of SNARE formation of camphorol, myricetin, and ampelopsin. (Cell line: C2C12 (muscle cell) + NG108-15 (nerve cell) condition, concentration: ppm)

Figure 5 is a graph showing the results of comparing the ampelopsin content in pig skin and acceptor solution.

Figure 6 is a graph showing the results of confirming the wrinkle improvement effect of the Amfellopsin cream and Amfellopsin microneedle in the human body.

Fig. 7 shows the results of confirming the muscle contraction inhibitory effect of camphorol, myricetin, and ampelopsin.

8 is a graph confirming magnesium gluconate content in pig skin and acceptor solution of magnesium gluconate cream and magnesium gluconate microneedle.

Figure 9 shows the results of measuring the inhibitory effect of In Vitro muscle contraction of magnesium gluconate. After incubation of myocytes and neuroblasts in vitro and treatment of magnesium gluconate by concentration, the results show that the number of muscle contractions decreases after 10 minutes.

Figure 10 graphically shows the wrinkle improvement index of magnesium gluconate cream and magnesium gluconate microneedle.

Hereinafter, examples and the like will be described in detail to help understand the present invention. However, embodiments according to the present invention can be modified in many different forms, the scope of the invention should not be construed as limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

Soluble Micro Needle is manufactured by solution casting method. The solution is cast into a mold, filled with liquid in a micro mold by vacuum or centrifuge, and then dried. At this time, general synthetic and natural water-soluble polymers are used to form the micro needle structure. .

To prepare a microneedle having the composition of Table 1. Dissolve Hyaluronic acid (Oligo-HA ™), Sodium carboxymethyl cellulose (Na-CMC) and Trehalose in purified water, and then use a solution of Glycerin, PEG-40 hydrogenated castor oil (HCO-40 ™) and Amfellopsin (10% Amfellopsin, DPG 90). %) Was added to prepare an amfellopsin solution (DPG: Dipropylene glycol). The prepared polyphenol dispersion solution was cast on a silicone micro needle mold, and then centrifuged at 3,000 rpm for 10 minutes to fill the liquid in the micro mold.

After the solution was filled and dried in a drying oven (70 ° C.) for 3 hours, the micro needle was separated from the silicone mold using an adhesive film. The content of Table 1 is expressed in weight percent.

The manufacturing process is shown in FIG.

In order to compare the skin permeation amount of the polyphenol impregnated with the microneedle, the polyphenol was impregnated and compared with a general oil-in-oil type cream as a comparative example.

Amphelopsin release from the microneedle prepared above was evaluated using a Franz diffusion cell equipped with pig skin (see FIG. 2). As an aqueous solution (acceptor solution) was used a PBS solution containing 30% by weight of DPG.

In other words, using a Franz diffusion cell, the ampelopsin content of the pig skin tissue and acceptor solution over time was measured using Liquid Chromatography.

The cream containing ampelopsin was minimal in permeation through the skin, but the ampoulescin impregnated in the Micro Needle penetrated directly into the skin by the needle, and the permeation amount was higher than that of the cream.

Cream containing ampelopsin was about 1ug permeated through the skin, but the amount was small.However, polyphenol impregnated in the microneedle penetrated directly into the skin by the needle, and its permeation amount was 13ug or more, which was 13 times higher than the cream. Skin permeation amount is shown. The result is shown in FIG.

Ampelopsin cream and Ampelopsin-impregnated Microneedle were treated daily for 12 weeks on the wrinkles of the eyes, and the degree of wrinkle improvement was confirmed by a silicone replica and a wrinkle image analysis method. (N = 20)

Compared to ampellopsin cream, ampellopsin-impregnated microneeedle showed more than 5 times better improvement, and it was confirmed that ampelopsin was effectively penetrated into the skin by the microneedle, resulting in a high wrinkle improvement effect. These results are shown in FIG.

Inhibition of SNARE complex formation

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis was performed to determine whether the polyphenols such as ampelopsin, camphorol and myricetin inhibit SNARE complex formation. It was confirmed whether the complex formed when the SNARE25, SynH3, and Vps proteins, SNARE proteins, were mixed at a molar concentration of 1: 1: 1 was inhibited by the addition of a polyphenol compound at a concentration of 1-50 ppm. Each protein was dropped into a 1 ml tube, and then mixed with a polyphenol compound, followed by reaction at room temperature for 30 minutes. Thereafter, electrophoresis on 12% SDS-PAGE confirmed the formation of SNARE complexes.

Camperol, myricetin and ampelopsin have all been found to effectively inhibit the SNARE complex in a concentration dependent manner. As a result, it was confirmed that the activity of inhibiting SNARE complex formation at low concentrations of camphorol and ampelopsin was higher than that of myricetin. Inhibition of SNARE formation of myricetin, ampfellopsin (dihydroxymyricetin), camphorol, and A440 was confirmed and shown in FIG. 4. (Cell line: C2C12 (muscle cell) + NG108-15 (nerve cell) condition, concentration: ppm)

Muscle contraction suppression experiment

C2C12 cells were cultured in DMEM medium containing 10% fetal calf serum and 1% antibiotics on plates. Neuroblasts were then further co-cultured on the same plate. After that, when the cell contraction of C2C12 cells starts, measure the number of contractions of C2C12 cells for 30 seconds, remove all the medium, wash them three times with PBS, and add the calf serum-containing medium and 50 ppm of polyphenolic compound for 2 hours. I was. Afterwards, the contraction frequency of C2C12 cells was measured again for 30 seconds to confirm the degree of muscle contraction inhibition.

Camperol, myricetin and ampelopsin inhibited the release of neurotransmitters from neurons, reducing the number of C2C12 cell contractions. Among them, the effect of inhibiting the release of amfellopsin and camphorol compared to myricetin was relatively high. The result is shown in FIG.

When preparing a cosmetic composition comprising ampelopsin of the present invention, it may include less than 0.5% (PEG400 5%, based on 70% water) ampelopsin, the microneedle manufactured by the method of manufacturing the microneedle of the present invention Amfellopsin content can be increased to around 5% of the microneedle dry weight. Thus, a product containing a high concentration of polyphenols can be produced.

Soluble microneedle is manufactured by the solution casting method, the solution was cast by casting the mold to the mold by vacuum or centrifuge the liquid was prepared by drying.

As the material for forming the microneedle structure, general synthetic and natural water-soluble polymers were used.

After dissolving Oligo-HA (Hyaluronic acid), Na-CMC (Sodium carboxymethyl cellulose) and Trehalose in purified water, Glycerin, HCO-40 and magnesium gluconate were added to prepare a magnesium gluconate solution. (DPG: Dipropylene glycol)

The magnesium gluconate dispersion solution was cast into a silicone microneedle mold, and then centrifuged at 3000 rpm for 10 minutes to fill the micro mold with liquid. After the solution was filled and dried for 3 hours in a drying oven (70 ℃), the microneedle was separated from the silicone mold by using an adhesive film.

Oil-in-water emulsion impregnated with magnesium gluconate

In order to compare the skin permeation amount of magnesium gluconate impregnated in the microneedle, magnesium gluconate was impregnated into the cream of the general oil-in-water emulsion as an example.

Using a Franz diffusion cell, the magnesium gluconate content of pig skin tissue and acceptor solution over time was measured by Liquid Chromatography. Magnesium gluconate cream was applied to porcine skin or microneedle impregnated with magnesium gluconate was used to compare skin penetration of magnesium gluconate over time.

Cream containing magnesium gluconate is less than about 1 ug permeated through the skin, but the amount of magnesium gluconate impregnated in the microneedle penetrates directly into the skin by the needle, and the permeation amount is 20 ug or more, about 20 times or more. It showed a higher skin penetration than the cream. The results are shown in FIG.

In Vitro muscle contraction inhibitory effect

As can be seen in Figure 9, when treated with magnesium gluconate, it was confirmed that the increase in the concentration of magnesium gluconate showed a tendency to significantly reduce the number of muscle contractions.

Magnesium gluconate cream and Magnesium gluconate-impregnated Microneedle was treated daily for 12 weeks on the wrinkles around the eyes, and the degree of wrinkle improvement was confirmed by using a silicone replica and a wrinkle image analysis method. (N = 20)

As can be seen in Figure 10, compared with magnesium gluconate creams showed an improvement of more than two to three times in the magnesium gluconate-impregnated microneeedle, which effectively penetrates the skin by the microneedle, wrinkle improvement effect Was found to be high.

The present invention can be used for cosmetics, pharmaceuticals for skin wrinkle improvement.

The microneedle of the present invention can expect excellent skin wrinkle reduction effect.

Claims

Microneedles containing ingredients that regulate the release of neurotransmitters.
The microneedle of claim 1, wherein the component that modulates the release of neurotransmitters is i) polyphenols or derivatives thereof, ii) calcium channel blockers, or iii) mixtures thereof.
The method of claim 2, wherein the polyphenol or derivatives thereof are camphorol, quercetin, myricetin, luteolin, delcinidine, cyanidin, butane, ellagic acid, ampfellopsin, hesperidin, aurantinidine, eurofini. Microneedle, characterized in that any one or more selected from the group consisting of dine, pelagonidine, malbidine, peonidine, petronidine, and rosinidine and derivatives thereof.
The microneedle of claim 3, wherein the polyphenol is ampelopsin, hesperidin or a derivative thereof.
The microneedle of claim 1, wherein the microneedle contains 0.01 to 10% by weight of polyphenol or a derivative thereof based on the total weight of the microneedle.
The method of claim 2, wherein the calcium channel blocker is copper gluconate, zinc gluconate, magnesium sulfate, magnesium gluconate, and magnesium aspatate. Organometallic compounds selected from the group consisting of one or more;

At least one dihydropyridine calcium channel blocker selected from the group consisting of amlodipine, lercanidipine, felodipine, nifedipine, nicardipine, isradinine, nisoldipine and pharmaceutically acceptable salts thereof;

Phenylalkylamine based calcium channel blockers including verapamil;

Benzothiapine-based calcium channel blockers including dithiazem; And

N-type calcium channel blockers selected from the group consisting of gabapentinoids and zinconotides; Microneedle, characterized in that any one or more selected from the group consisting of.
7. The microneedle of claim 6, wherein the calcium channel blocker is magnesium gluconate.
The microneedle of claim 1, wherein the microneedle is dissolved in the skin.
The material of claim 1, wherein the material forming the microneedle is hyaluronic acid, sodium-carboxymethyl cellulose, sodium carboxymethyl cellulose (Na-CMC), vinylpyrrolidone-vinylacetate copolymer, or polyvinyl alcohol ( Poly vinyl alcohol), poly vinyl pyrrolidone, microneedle, characterized in that the sugar or a mixture thereof.
10. The microneedle of claim 9, wherein the microneedle further comprises a plasticizer in addition to the material forming the microneedle.
A microneedle for improving skin wrinkles, comprising the microneedle according to any one of claims 1 to 10.
Claim 1 to 10, characterized in that to improve the wrinkles of the skin using the microneedle according to any one of claims 1 to 10, the method of skin administration of a component for controlling the release of neurotransmitters.
Skin wrinkle improvement for microneedles containing ingredients that regulate the release of neurotransmitters.