KR20180011837A - Composition for microstructure comprising organic solvent, and Method of preparing microstructure using the same - Google Patents

Abstract

The present invention relates to a composition for a microstructure, which can manufacture a structure by dissolving a hydrophobic drug or a hydrophilic drug with a biocompatible material by only an organic solvent, and to a method for manufacturing a microstructure using the composition. The microstructure of the present invention can manufacture a microneedle structure containing a drug by using an organic solvent without using water at all. The micro-structure of the present invention uses a biocompatible material soluble in water as well as in an organic solvent as a skeletal material. Thus, a hydrophobic drug or a hydrophilic drug can be contained in a needle structure, and the structure is easily dissolved when the being inserted into the skin to transfer the drug into the skin. The composition or the method of the present invention do not use water, and thus is very efficient because the drying time of the structure can be reduced and the process and drying temperatures can be lowered. In addition, the present invention uses only an organic solvent, and thus can improve solubility of a liposoluble drug compared to a conventional method in which water is added only. As a result, the present invention can contain a large amount of hydrophobic drugs in the structure compared to the conventional method. Accordingly, the number of needles required to deliver a desired amount of a drug can be reduced, and a size occupied by a patch can be reduced.

Description

TECHNICAL FIELD The present invention relates to a composition for a microstructure including an organic solvent and a method for manufacturing a microstructure using the same,

  The present invention relates to a composition for a microstructure comprising an organic solvent and a method for producing a microstructure using the same, and more particularly to a composition for a microstructure capable of producing a structure by dissolving a hydrophobic or hydrophilic drug and a biocompatible material only in an organic solvent And a method of manufacturing a microstructure using the same.

Currently, commercialized drug delivery systems are largely divided into oral preparations, injections, and transdermal preparations. Among them, oral administration is the most common and convenient method, but it causes limitation of drug degeneration and absorption due to gastrointestinal tract, and most of proteins and DNA constructs such as insulin and hormone drugs are decomposed by the gastrointestinal tract and are difficult to be effectively used.

Injection is also the fastest and most effective method of drug delivery, but patient suffering and rejection of needles not only causes mental stress on the patient, but also requires the help of professional medical personnel and difficulties in repeated administration.

To overcome these disadvantages, new methods of transdermal administration have been developed. In the case of the transdermal drug delivery system, it is possible to avoid the gastrointestinal disorder by transferring the drug through the skin, and it is possible to reduce the pain and rejection of the patient when the drug is administered. However, in the case of transdermal drug delivery, the molecular weight of the drug delivered by the stratum corneum present in the outermost layer of the skin is only 500 Da or less, and there is a limit to an effective drug delivery system due to differences in the amount and rate of delivery depending on the type of drug .

In order to overcome this problem, new systems such as iontophoresis, electrophoresis, heating, microneedle, and chemical enhancer have been developed. However, there are limitations in transferring a sufficient amount of the drug.

In the case of the micro needle, the length of the drug can be adjusted to 90 ~ 1500 ㎛ according to the purpose of drug delivery by transmitting a drug through a small hole on the surface of the skin. This form is a physical puncture of the horny layer, which is the outermost layer of the skin, through which the drug is delivered. However, these conventional microneedle systems are difficult to transfer sustained drug delivery due to the small size of the holes formed and the holes of the skin due to the passage of time. Especially, it is difficult to transfer nanocarrier such as nanoparticle and liposome through the holes formed.

In addition, when a drug is coated on a needle or a drug is added to a water-soluble needle, a water-soluble drug is limited due to limitations of the water-based manufacturing process, and it is difficult to transfer a large amount of drug due to the solubility limit of the drug.

References (Polymer microneedles for transdermal drug delivery

, Journal of Drug Targeting April 2013, Vol. 21, No. 3, Pages 211-223), the materials that are transferred to the micro needle or under development are hydrophilic materials, which is due to limitations in the needle manufacturing process. Therefore, if a hydrophobic drug can be delivered through the skin using a microdevice, many drugs that have been developed or under development can be delivered and applications will increase.

       [Model drugs currently being delivered or developed using micro-needles]

Hydrophobic drugs have a high distribution coefficient to lipid, which is faster in transduction and absorption than other routes in transdermal delivery. Therefore, the transdermal delivery method of a hydrophobic drug using a microdevice is capable of delivering a drug with a high molecular weight and a high molecular weight.

The inventors of the present invention prepared a micro needle by mixing a hydrophobic drug and a biocompatible material using a mixed solvent of water and alcohol (Patent Registration No. 10-1513812). The above-mentioned patent effectively contained hydrophobic drugs compared to conventional micro needles and was able to deliver them into the body. However, there is still a need for a method of manufacturing microstructures that can increase the content of hydrophobic drugs and improve the manufacturing time and process conditions of the needle compared to the above-mentioned registered patent. At the same time, the manufactured micro needles must have the strength to penetrate the skin.

  In the case of microneedles, the needle structure is small, so that the content of drugs that can be contained based on water, which is a widely used solvent, is low. The present invention provides microstructures that can contain large amounts of hydrophobic drugs or hydrophilic drugs.

The present invention provides a method for lowering the processing time and temperature of a structure.

The present invention provides a smart transdermal drug delivery structure capable of delivering target-directed drugs to a desired site or cell by controlling the amount and rate of drug release.

The present invention relates to a composition comprising a biocompatible material, a hydrophobic drug and an organic solvent, wherein the biocompatible material forms a skeleton of a microstructure as a polymer soluble in water as well as the organic solvent, Which is a dissolvable drug.

The present invention relates to a composition comprising a biocompatible material, a hydrophilic drug and an organic solvent, wherein the biocompatible material forms a skeleton of a microstructure as a polymer soluble in water as well as the organic solvent, And to a composition for producing microstructures which is a dispersible drug.

The present invention relates to a method for producing microstructures using the composition.

The microstructure of the present invention can be used to prepare a drug-containing micro needle structure using an organic solvent without using any water. Since the microstructure of the present invention uses a biocompatible material soluble in water as well as an organic solvent as a skeleton material, it can contain a hydrophobic drug or a hydrophilic drug in the needle structure, and when the structure is inserted into the skin, To the inside of the skin. Since the composition and the manufacturing method of the present invention do not use water, the drying time of the structure can be reduced and the process and the drying temperature can be lowered, which is very efficient.

In addition, since the present invention is used only as an organic solvent, the solubility of the hydrophobic drug can be increased as compared with the conventional method in which water is added. As a result, the present invention can contain a large amount of hydrophobic drug . This reduces the area of the microneedles needed to deliver the appropriate amount of drug.

The method of the present invention can produce a desired amount of hydrophobic drug through the skin or the mucous membrane without loss of drug during the manufacturing process.

The microstructure of the present invention can selectively and locally deliver hydrophobic drugs effectively and stably to desired sites such as cancer, muscle, and cell.

1 is a schematic view showing a microstructure which is one embodiment of the present invention.
2 is a schematic view showing a step of manufacturing the microstructure of the present invention.
3 is an image of microstructures prepared in Examples 1 and 2, Comparative Example 1, and Reference Example 1.
4 is a graph showing the degree of permeation after inserting the microstructures prepared in Examples 1 to 4 and Comparative Example 1 into the skin.
FIG. 5 is an image showing a time-course that the microstructure prepared in Example 1 is dissolved in the skin after it is inserted.
FIG. 6 is a graph showing the drying time of the structure according to Examples 5 and 6 and Comparative Examples 2 to 4; FIG.
Fig. 7 shows the microstructure produced in Example 7. Fig.
8 is an image photograph of the microstructure manufactured in Example 8. Fig.

The present invention relates to a composition for a microstructure comprising an organic solvent and a method for producing a microstructure using the same.

The composition for a microstructure of the present invention includes a biocompatible material, a hydrophobic drug, and an organic solvent.

The biocompatible material uses a material capable of forming a skeleton of a microstructure as a polymer soluble in water as well as the organic solvent. That is, when the biocompatible material is dissolved in an organic solvent together with the hydrophobic drug in the process of constructing the structure, the skeleton of the structure containing the hydrophobic drug should be formed when it is dried, and when the structure is inserted into the skin, The substance must be able to dissolve and release the drug by the water present in the skin layer.

In addition, the biocompatible material is a substance having affinity with a hydrophobic drug, and is preferably a material usable as a thickener or a coating agent. When the biocompatible material is dissolved in the organic solvent And may have a viscosity in the range of 6 to 3000 cps.

In addition, in order to be used as a biocompatible material, it is preferable to use a polymer material having biological stability as a material having a predetermined mechanical strength. Furthermore, the biocompatible material for use in the present invention should be capable of being degraded by body fluids, microorganisms, and the like in vivo. The biocompatible materials satisfying the above conditions are cellulose acetate, fructose, hydroxypropyl betadex, hydroxypropyl cellulose (USP grade), hypromellose (HPMC), lactose anhydrous, Macrogol 15 hydroxystearate, maltodextrin, methylcellulose, poloxamer, polydextrose, It may be at least one selected from the group consisting of polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene stearates, povidone, propylene glycol alginate, sodium acetate, sorbitol, sucrose, xylitol, zein and zinc acetate.

The organic solvent may suitably be selected from those capable of dissolving the biocompatible material and the hydrophobic or hydrophilic drug. The organic solvents may be appropriately selected to have appropriate volatility and not remain in the structure after the production of the microstructure is finished, so as not to cause toxicity.

The organic solvent may be at least one selected from the group consisting of Dibutyl phthalate, Dimethyl phthalate, Ethyl lactate, Glycerin, Isopropyl alcohol, Lactic acid, Lauric acid, Linoleic acid, Propylene carbonate, Propylene glycol, Pyrrolidone and tricaprylin.

The hydrophobic drug may be a chemical drug, a protein drug, a peptide drug, a nucleic acid molecule and nanoparticle for gene therapy, an efficacy substance used in cosmetics, and the like. More specific examples include A-Methapred, Ziagen (Abacavir sulfate), Abiraterone acetate (Zytiga), Abraxane, Isotretinoin (Absorica), Abstral (Fentanyl Sublingual Tablets), Acantha gel (Clindamycin phosphate 1.2% and Benzoyl Peroxide 2.5% (Acarbose), Zafirlukast (Accolate), AccuNeb (Albuterol sulfate inhalation solution), Quinapril hydrochloride (Accupril), Accutane (isotretinoin), Accuzyme (Papain and urea), Acebutolol hydrochloride (Sectral), Aceon (Perindopril erbumine), Acetylcystein Acetylcysteine (Acetadote), Aciphex (Rabeprazole sodium), Acetylcholine Chloride (Acetylcholine Chloride), Acetylcholine (Acetaminophen), Acetaminophen, Acetaminophen, Isomethophene and Dicholraphenazone (Midrin), Acetazolamide, Acetic acid, Gantrisin , Acitretin (Soriatane), Aclidinium bromide (Tudorza pressair), Acrivastin and pseudoephedrine hydrochloride (Semprex-d), Acthrel (Corticorelin ovine triflutate), Acticin (Permethrin), Aclidinium b but are not limited to, trombiculone (Tudorza Pressair), Fentanyl citrate (Actiq), Tetracycline periodontal (Actisite), Alteplase (Activase), ACTOPLUS MET® (pioglitazone hydrochloride and metformin hydrochloride), Cyclosporine A, and Triamcinolone.

The composition may contain 1 to 250 parts by weight, preferably 1 to 100 parts by weight, and 500 to 3,000 parts by weight, preferably 600 to 2,000 parts by weight, of the hydrophobic drug with respect to 100 parts by weight of the biocompatible material .

The present invention can further add an increasing agent to the mixed solution to increase the mechanical strength of the microstructure. The amount of the thickener may be 0 to 100 parts by weight based on 100 parts by weight of the biocompatible material.

The increment may be selected from the group consisting of trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melitose, dextran, sorbitol, xylitol, palatinite, mannitol, poly (lactide) Polyether sulfone, poly (glycolide), poly (lactide-co-glycolide), polyanhydride, polyorthoester, polyetherester, polycaprolactone, but are not limited to, polyesteramide, poly (butyric acid), poly (valeric acid), polyurethanes, polyacrylates, ethylene-vinyl acetate polymers, acrylic substituted cellulose acetate, non-degradable polyurethanes, polystyrene, polyvinyl chloride, Poly (vinylimidazole), chlorosulfonate, chlorosulphonate polyolefins, polyethylene oxide, polyvinylpyrrolidone (PVP), poly (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethylcellulose, cyclodextrin, and monomers forming these polymers Or a combination of two or more substances selected from the group consisting of.

The composition of the present invention may further comprise a surfactant for enhancing the interaction between the drug and the biocompatible material. The surfactant may be added in an amount of 0 to 20 parts by weight based on 100 parts by weight of the biocompatible material.

Examples of the surfactant include, but are not limited to, polyethylene glycol, polyoxyethylene (n = 10) oleyl ether, polyoxyethylene-9-nonylphenyl ether, polyethylene glycol-40 -Hydrogenated castor oil or octosinol-11 may be used.

The composition of the present invention can increase the solubility of the hydrophobic drug by using an organic solvent in which no water is added. As a result, the composition of the present invention can contain a large amount of hydrophobic drug in the structure .

In addition, the composition of the present invention may be a solution in which a hydrophilic drug is mixed with an organic solvent together with the biocompatible material. The aforementioned biocompatible materials, organic solvents, thickeners and surfactants can be referred to above.

The hydrophilic drug may be a drug that can be dispersed in the organic solvent. The hydrophilic drug may be an efficacious substance used in a protein / peptide drug, a chemical drug, or a cosmetic product. The protein / peptide medicament is not particularly limited, and includes a hormone, a hormone analogue, an enzyme, an enzyme inhibitor, a signal transduction protein or a part thereof, an antibody or a part thereof, a single chain antibody, a binding protein or a binding domain thereof, But are not limited to, proteins, regulatory proteins, toxin proteins, cytokines, transcription factors, blood coagulation factors, and vaccines. More specifically, the protein / peptide medicament may be selected from the group consisting of insulin, insulin-like growth factor 1 (IGF-1), growth hormone, erythropoietin, granulocytecolony stimulating factors (G-CSFs), granulocyte / interleukin-2, EGFs (epidermal growth factors), calcitonin, interleukin-1, interleukin-1, interleukin-3, interleukin- The compounds of the present invention may be used in combination with other therapeutic agents such as ACTH (adrenocorticotropic hormone), TNF (tumor necrosis factor), atobisban, buserelin, cetrorelix, deslorelin, desmopressin, Dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, growth hormone releasing hormone-II (GHRH-II), gonadolerin gonadorelin, goserelin, histrelin, leuprorelin, lyphresin, pressin), octreotide, oxytocin, pitressin, secretin, sincalide, terlipressin, thymopentin, thymosine, ) alpha 1, triptorelin, bivalirudin, carbetocin, cyclosporine, exedine, lanreotide, luteinizing hormone-releasing hormone (LHRH) But are not limited to, nafarelin, parathyroid hormone, pramlintide, T-20 (enfuvirtide), thymalfasin, chiconotide, Donepezil Hydrochloride (Aricept) or Lidocaine HCl.

The composition may contain 1 to 250 parts by weight, preferably 1 to 100 parts by weight, and 500 to 3,000 parts by weight, preferably 600 to 2,000 parts by weight, of the hydrophilic drug relative to 100 parts by weight of the biocompatible material .

In another aspect, the invention relates to a method of making microstructures using the composition.

1 is a schematic view showing a microstructure fabricated by the above method. Referring to FIG. 1, the microstructure includes a support plate 10 and a needle 20.

The microstructure may be formed of a micro needle, a micro spike, a micro blade, a micro knife, a micro fiber, a micro probe, a micro bar, a micro array or a micro electrode, more preferably a micro needle.

The present invention can be fabricated by a variety of methods known in the art using the above-described compositions described above.

The above-mentioned structure manufacturing method can use any conventionally known methods without limitation. For example, Japanese Patent Application Laid-Open No. 2005154321 proposed by Nano Device & And " Sugar Micro Needles as Transdermic Drug Delivery System " (Biomedical Microdevices 7: 3, 185-188, 2005). Further, a method of producing a biodegradable polymer micro-needle by making a template by photolithography (Fabrication, mechanics and transdermal drug delivery, Journal of Controlled Release 104, 51-66, 2005) can be referred to.

In addition, a known soft lithography technique may be used to prepare an elastomeric mold such as PDMS (polydimethylsiloxane) and use it in the production of liposome-microstructures. The PDMS mold manufacturing technology is a kind of plastic processing technique, and a desired molding structure can be obtained by various methods such as casting, injection, hot-embossing, and the like. For example, a photosensitive material is coated on a substrate such as a silicon wafer or glass, and patterned using a photomask, resulting in a master. When the PDMS is cast and sintered with the mold, a PDMS mold having a stamp function can be completed.

The microstructure may be prepared by injecting the composition into a micro mold (PDMS mold) and then drying the microstructure.

More specifically, the manufacturing method using a micro-mold includes the steps of injecting the composition into a micro-mold, drying to remove the organic solvent, and removing the micro-mold.

2 is a schematic view showing a step of manufacturing a microstructure of the present invention using a micro-mold. Referring to Figure 2, the method comprises the steps of: (a) providing a micro-mold, (b) feeding the composition onto the micro-mold, (c) injecting the composition into a hole formed in the mold, (d) Drying, and (e) removing the mold.

In addition, the present invention can produce microstructures in various forms using the micro mold and the composition of FIG.

The preparation method of the present invention comprises the steps of preparing the composition containing a hydrophilic or hydrophobic drug, firstly injecting a composition containing the hydrophilic or hydrophobic drug into the tip region of the micro-mold, A step of injecting a biocompatible material containing a hydrophilic or hydrophobic drug or a biocompatible material not containing a drug onto the tip region of the micro mold in a second order, drying and removing the organic solvent, and removing the micro mold, ≪ / RTI >

For example, a composition containing the hydrophilic drug is supplied onto a mold so that only a part of the hole (for example, within 1/2 of the hole of the needle) is filled, and then the drug- The composition consisting solely of a compatible material may be injected into the hole. In the case of manufacturing by such a method, hydrophilic drugs can be contained only in the needle tip portion of the microstructure to enable quantitative transfer. Also, a composition containing the hydrophilic drug may be supplied onto the mold, and injected to fill the entire hole.

Likewise, the manufacturing method of the present invention can be manufactured by injecting a composition containing a hydrophobic drug into a part of the hole and then injecting a composition in which the drug is not present, and filling a composition containing the hydrophobic drug into the hole As shown in FIG.

Another method of fabricating the microstructure is to apply the composition onto a substrate, and then use the support to lift and dry the composition.

More specifically, a method of making using lifting includes coating the composition on a substrate, contacting the support with the composition, and lifting to form a microstructure.

The support has a protrusion, and the protrusion contacts the composition. The method involves drawing the composition by raising the lift to a predetermined height when the composition is in contact with the projection.

The drying step for evaporating the solvent can be carried out at the same time as before or after the lifting. When the microstructure is dried and solidified, the structure can be separated from the support.  

Hereinafter, the present invention will be described in more detail with reference to examples, but these examples should not be construed as limiting the scope of protection of the present invention.

Example  1 to 4, Reference example , Comparative Example  One

(C = 10%, 25 ^o C water) and CyA (Cyclosporin A) as a hydrophobic drug were mixed in methanol at the ratios shown in Table 2, .

The composition was mixed with 0.25 g of the mixed solution in a hole formed in the mold, followed by centrifugation at 10 DEG C at 3000 rpm (1942 g) for 20 minutes. After drying at 25 ° C for 4 to 6 hours, the mold was removed to obtain a drug delivery microstructure.

division HPC: CyA (weight ratio) Methanol Reference example 10: 0 (HPC + CyA) was dissolved in methanol to prepare 21.8% (w / w) Example 1 9: 1 Example 2 5: 5 Comparative Example 1 3: 7

3 is an image of microstructures prepared in Examples 1 and 2, Comparative Example 1, and Reference Example 1. Referring to FIG. 3, it can be seen that, in the case of Comparative Example 1 (containing 70% or more of CyA), a portion of the tip is distorted during removal of the structure from the mold.

Table 3 below shows the drug content of the prepared microstructure by HPLC. (Example 3 was a microstructure prepared by using HPC: CyA (weight ratio) of 9.5: 0.5.

division CyA expected content
(In 1.2 mg needle tip) Measured value (㎍) ratio Example 3 60 58.9654 + 0.3889 98.9654 + 0.3889 Example 1 120 113.5124 ± 2.1004 94.5937 + 1.7504 Example 2 600 595.1965 ± 12.3160 99.1994 ± 2.0527

Table 3 shows that there is no significant difference in the content of the drug contained in the microstructure relative to the injected drug.

4 is an image and a graph showing the degree of permeation after inserting the microstructures prepared in Examples 1 to 4 and Comparative Example 1 into the skin. In Example 4, a microstructure was prepared in the same manner as in Example 1, except that HPC: CyA (weight ratio) was changed to 7: 3.

4, when the content of the drug (CyA) exceeds 50% of the biocompatible material, the mechanical strength starts to decrease. Particularly, when the drug content is 70% (Comparative Example 1) . ≪ / RTI > In contrast, Example 1, Example 3 and Example 4 show a very high transmittance of 90%. In the case of Example 2, the transmittance is as high as about 85%. FIG. 4 shows that the microstructure can function as a drug delivery system efficiently when it contains less than 50% of the drug.

FIG. 5 is an image showing a time-course that the microstructure prepared in Example 1 is dissolved in the skin after it is inserted. Referring to FIG. 5, it is shown that more than 50% of the structure is decomposed after 5 minutes, and most of the structure is dissolved when 10 minutes have elapsed. That is, the microstructure of the present invention carries a hydrophobic drug, but when it is inserted into the skin, it is mostly dissolved within 10 minutes, so that it can be an effective drug delivery system.

Example  5

1 g of HPC (Sigma aldrich, average Mw ~ 80,000, viscosity 250-800 cps (c = 10%, 25 ^o C water)) was added to 5 ml of methanol to prepare a composition (no drug added).

The composition was mixed with 0.25 g of the mixed solution in a hole formed in the mold, followed by centrifugation at 10 DEG C at 3000 rpm (1942 g) for 20 minutes. After drying at 25 ° C for 4 to 6 hours, the mold was removed to obtain a drug delivery microstructure.

Example  6

Was prepared in the same manner as in Example 5, except that 5 ml of ethanol was used instead of methanol.

Comparative Example  2

Was prepared in the same manner as in Example 5, except that 5 ml of water was used in place of methanol.

Comparative Example  3

Was prepared in the same manner as in Example 5, except that 5 ml of a mixed solvent of methanol and water (80% methanol) was used instead of methanol.

Comparative Example  4

Was prepared in the same manner as in Example 5, except that 5 ml of a mixed solvent of ethanol and water (80% of ethanol) was used instead of methanol.

FIG. 6 is a graph showing the drying time of the structure according to Examples 5 and 6 and Comparative Examples 2 to 4; FIG.

Referring to FIG. 6, in Examples 5 and 6, the drying speed was 2.5 times or more as compared with Comparative Example 2 where water was used as a solvent. In addition, Examples 5 and 6 show higher drying rates than Comparative Example 3.4 where water and organic solvent are mixed.

Example  7

0.9 g of HPC (Sigma aldrich, average Mw ~ 80,000, viscosity 250-800 cps (c = 10%, 25 ^o C water)) was added to 5 ml of methanol to prepare a mixed composition of 18% (no drug was added) . About 10 ml of the mixed composition was applied onto the substrate. And was dried for about 10 to 15 seconds at an air speed of 300 L / min while the temperature was raised to 50 DEG C while being lifted upwards using a tweezers.

Fig. 7 shows the microstructure produced in Example 7. Fig. Referring to FIG. 7, the composition of the present invention shows that a microstructure can be prepared by a drawing method.

Example  8

0.36 g of HPC (Sigma aldrich, average Mw ~ 80,000, viscosity 250-800 cps (c = 10%, 25 ^o C water)) and 0.04 g of Donepezil HCl or Lidocaine HCl as a hydrophilic drug were mixed in 1.6 ml of methanol to prepare a composition .

The composition was mixed with 0.25 g of the mixed solution in a hole formed in the mold, followed by centrifugation at 10 DEG C at 3000 rpm for 20 minutes. After drying at 25 ° C for 4 to 6 hours, the mold was removed to obtain a drug delivery microstructure.

8 is an image photograph of the microstructure manufactured in Example 8. Fig. to be. Referring to Fig. 8, the microstructure produced in Example 8 has a sharp needle tip without distortion.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. Those skilled in the art will readily appreciate that various changes, modifications, and variations may be made without departing from the spirit and scope of the invention, the foregoing description and the annexed drawings.

Claims (8)

A composition comprising a biocompatible material, a hydrophilic drug and an organic solvent, wherein the biocompatible material forms a skeleton of a microstructure as a polymer soluble in water as well as the organic solvent, and the hydrophilic drug is a drug capable of dispersing in the organic solvent Wherein the microstructure comprises at least one of the following. The biocompatible material of claim 1, wherein the biocompatible material is selected from the group consisting of cellulose acetate, fructose, hydroxypropyl betadex, hydroxypropyl cellulose (USP grade), hypromellose (HPMC), lactose anhydrous, Macrogol 15 hydroxystearate, maltodextrin, methylcellulose, poloxamer, polydextrose, characterized in that it is at least one selected from the group consisting of polyoxyethylene alkyl ethers, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene stearates, povidone, propylene glycol alginate, sodium acetate, sorbitol, sucrose, xylitol, Composition. The composition for preparing a microstructure according to claim 1, wherein the organic solvent is at least one selected from the group consisting of alcohols, glycerin, isopropyl alcohol, propylene carbonate and propylene glycol. The composition for preparing a microstructure according to claim 1, wherein the hydrophilic drug is a protein / peptide drug, a chemical drug, a nucleic acid molecule for gene therapy, nanoparticles, or an efficacious substance used in cosmetics. The composition of claim 1, wherein the composition comprises about 100 parts by weight of the biocompatible material
1 to 100 parts by weight of the hydrophilic drug and 500 to 3,000 parts by weight of an organic solvent. Preparing a composition of claim 1;
Injecting the composition into a micro-mold;
Drying the organic solvent to remove the organic solvent; And
And removing the micro-mold to obtain a microstructure. Preparing a composition of claim 1;
Coating the composition on a substrate;
Contacting the support with the composition and lifting to draw the microstructure,
Wherein the method comprises the step of drying the organic solvent before or after the drawing step. Preparing a composition of claim 1;
Injecting the composition of claim 1 first into the tip region of the micro-mold;
Injecting the composition or biocompatible material of claim 1, which has not been injected in the first injection step, onto the tip region of the micro mold secondarily;
Drying the organic solvent to remove the organic solvent; And
And removing the micro-mold to obtain a microstructure.

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