KR20170044049A - Microstructure and method for fabricating thereof using gel-type polymer material - Google Patents

Abstract

The present invention relates to a microstructure and a production method thereof. The microstructure is produced by the following steps: a step (a) for forming a polymeric substance-containing gelated base region on a support; and a step (b) for forming an external region on the gelated base region. According to the present invention, formation of the microstructure can be easily conducted even when the polymeric substance having high weight average molecular weight is used.

Description

TECHNICAL FIELD [0001] The present invention relates to a microstructure using a gel-like polymer material and a method of manufacturing the microstructure,

The present invention relates to a microstructure using a gel polymeric material and a method of manufacturing the same.

Subcutaneous drug injection methods are one of the methods commonly used for various disease treatment and drug delivery. Subcutaneous drug injection has advantages such as lower drug degradation and degradation rate, higher drug delivery efficiency in the body, and reduced side effects through drug delivery in comparison with the oral drug delivery method which is absorbed while passing through the internal digestive organs. Currently, hypodermic needles of various diameters are widely used as subcutaneous drug injection methods.

 Conventional hypodermic needles are used in most drug delivery methods. However, skin damage and pain are inevitable when the skin is inserted according to the length and diameter of the hypodermic needle, and side effects such as allergic reaction due to metal materials and needle phobia due to pain occur. Particularly, in the case of a specific disease requiring repetitive drug injection for a short period of time, it is impossible to perform the same site injection due to the scarring which occurs when the conventional subcutaneous injection is used, and there are problems such as reduction of convenience of patient and reduction of drug injection efficiency.

In order to solve the problem of conventional hypodermic needles, a micro needle which can be injected subcutaneously into a microsize has been developed. The micro needle is a micro-sized structure that can solve problems such as pain, trauma, and reduced patient convenience of existing hypodermic needles, and biodegradable micro needles can be minimally invasive and deliver painless drugs. Research field. Existing biodegradable micro needles were fabricated by cast molding, tensile molding, tensile blow molding. In the case of the molding process, it is essential to fill the micro-sized mold with the viscous solution. Thus, there is a disadvantage that the length of the biodegradable microneedle that can be manufactured is high and the loss rate is high in the manufacturing process. The stretching method and the tension blowing method are performed by forming a micro needle structure by using a viscosity of a viscous solution to form a biodegradable micro needle by a drying process. However, when a high molecular weight polymer material is used, it is impossible to produce a viscous solution. However, when a low molecular weight polymer material is used, the structure of the biodegradable micro needle is difficult to form and the strength thereof becomes weak.

(A) forming a gel-like base region comprising a polymeric material on a support; And (b) forming an outer region on the gel-type base region.

However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.

(A) forming a gel-like base region comprising a polymeric material on a support; And (b) forming an outer region on the gel base region

A method of manufacturing a microstructure is provided.

In (a), the weight average molecular weight of the polymeric material may be from 50 kDa to 2,500 kDa.

The viscosity of the gel-like base region in (a) may be 5 Pa · s to 400 Pa · s at 25 ° C.

In the step (a), the gel strength of the gel-type base region may be 0.03 N to 5N.

In the step (a), the gel base region may be divided into multiple base regions.

The drug may be further loaded in the gel-type base region in step (a) or inside the outer region in step (b).

In the step (a), the formation of the gel base region may be performed by discharging, attaching, punching or molding.

A pre-coating layer may be formed on the support in advance.

The method may further include the step of modifying the gel base region simultaneously with the formation of the gel base region in the step (a), or after the formation of the gel base region in the step (a).

In the step (b), the formation of the outer region is performed by coating the coating region including the second polymeric material on the gel base region, and the second polymeric material has a weight average molecular weight or viscosity . ≪ / RTI >

In the step (b), formation of the outer region may be performed through attachment of the second micro-structure on the gel-type base region.

The coating area can be divided into multiple coating areas.

The coating can be carried out by discharging, immersing or spraying.

After the coating, the coating region may be formed, or a separate microstructure may be deposited on the coating region.

The molding may be performed by one or more methods selected from the group consisting of molding, drawing, blowing, suction, centrifugal force application, and magnetic field application.

In one embodiment of the present invention, microstructures prepared according to the above method are provided.

According to another embodiment of the present invention, there is provided a semiconductor device comprising: a base layer including a polymer material; And an outer layer comprising a second polymeric material formed on the base layer, wherein the second polymeric material has a smaller weight average molecular weight or viscosity than the polymeric material.

The weight average molecular weight of the polymer material may be from 50 kDa to 2,500 kDa.

The viscosity of the polymeric material may be from 5 Pa · s to 400 Pa · s at 25 ° C.

In the case of the method for producing a microstructure using the gel polymer material according to the present invention, even when a polymer material having a high weight average molecular weight is used, the structure of the microstructure is easily formed and the strength of the microstructure can be improved. In addition, when applied to human body, it is possible to administer a high-molecular-weight substance or drug in the human body.

1 is a view illustrating a method of manufacturing a microstructure using a gel polymer material according to various embodiments of the present invention.
2 is a view showing various materials and various types of supports.
Figure 3 is a view showing a gel base region formed in various diameters, various heights, and various shapes.
Figure 4 is a diagram illustrating the formation of a gel base region by various methods.
FIG. 5 is a view showing a precoat layer of various materials. FIG.
6 is a view showing various modifications of the gel base region.
7 is a view showing a coating region formed in various shapes.
8 is a view showing the molding of the coating region.
9 is an electron micrograph showing the gel base region and microstructures prepared according to Examples 1 to 3. FIG.
10 is an electron micrograph showing the gel-type base region and microstructure fabricated according to Example 4. FIG.
11 is an electron micrograph showing the gel base region and microstructure fabricated according to Example 5. FIG.
12 is an electron micrograph showing a microstructure fabricated according to Example 6. Fig.

The inventors of the present invention have confirmed that microstructures having improved strength can be successfully prepared by forming a gel-like base region containing a polymer substance having a high weight average molecular weight, and have completed the present invention.

As used herein, the term "gel polymer material" refers to a polymer material having a high weight average molecular weight for forming a gel-like base region. The polymer material may be formed by crosslinking two or more low molecular materials, The two or more polymeric materials, which are the same or different, may form cross-linking.

As used herein, the term "gel-like" refers to a state in which the dispersion phase is solid and the dispersion medium is a liquid, which is a colloidal dispersion system, That is, the gel is a concept distinct from liquid (viscous solution) or solid.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings, which will be readily apparent to those skilled in the art to which the present invention pertains. The present invention may be embodied in many different forms and is not limited to the embodiments described herein.

In the drawings, the thickness is enlarged to clearly represent the layers and regions. In the drawings, for the convenience of explanation, the thicknesses of some layers and regions are exaggerated.

Hereinafter, the formation of an arbitrary structure in the above-mentioned "upper (or lower)" means not only that an arbitrary structure is formed in contact with the upper (or lower) And the present invention is not limited to the configuration including any other configuration.

Hereinafter, the present invention will be described in detail.

(A) forming a gel-like base region comprising a polymeric material on a support; And (b) forming an outer region on the gel-like base region.

1 is a view illustrating a method of manufacturing a microstructure using a gel polymer material according to various embodiments of the present invention.

As shown in FIG. 1, after forming a gel-like base region 20 containing a polymeric material on the support 10 (step (a)), a gel- Forming the outer region through the coating 30 and the molding 30 'of the coating region or by applying the coating 30 of the coating region comprising the second polymeric material on the gel base region 20 and the attachment of a separate microstructure (Step (b)) to form an outer region through the first microstructure 31, or to form an outer region through the attachment 40 of the second microstructure on the gel-like base region, to fabricate microstructures according to various embodiments (Step (c)).

First, a method of manufacturing a microstructure according to the present invention includes a step (a) of forming a gel-type base region containing a polymer material on a support.

The support is used for supporting a gel-like base region comprising a polymeric material.

2 is a view showing various materials and various types of supports.

As shown in FIG. 2, the support 10 may be formed of various materials such as a metal or a polymer material, and may have various shapes such as a substrate and a column. At this time, when the support is a substrate, it may have various surface shapes.

The present invention is characterized in that a gel base region containing a polymer material is used in order to overcome the limit of the weight average molecular weight of the polymer substance which can be included in the conventional viscous solution.

The present invention can be applied not only to a case where a gel base region including a polymer material formed directly on the support is used but a separate viscous solution is first formed on the support, And a gel base region including a polymer material formed thereon may be used.

The weight average molecular weight of the polymer material is preferably 50 kDa to 2,500 kDa, more preferably 1000 kDa to 2,500 kDa, but is not limited thereto. When the weight average molecular weight of the polymer material is less than the above range, there is a problem that gel formation is difficult. When the weight average molecular weight of the polymer material exceeds the above range, molding is difficult after gel formation.

At this time, the concentration of the polymer material may be dependent on the weight average molecular weight, and is preferably 5% (w / v) to 95% (w / v), but is not limited thereto. In this case, when the concentration of the polymer substance is less than 5% (w / v), gel formation itself is difficult, and when the concentration of the polymer substance exceeds 95% (w / v) .

That is, the polymeric material can effectively form a gel-type base region by simultaneously maintaining a weight average molecular weight of 50 kDa to 2,500 kDa and a concentration of 5% (w / v) to 95% (w / v).

In particular, the polymeric material may be a biocompatible or biodegradable material.

As used herein, the term " biodegradable material "refers to a material that is substantially non-toxic to the human body, chemically inert and non-immunogenic, and the term" biodegradable material " Material.

Examples of the biocompatible or biodegradable material include hyaluronic acid, polyester, polyhydroxyalkanoate (PHAs), poly (? -Hydroxyacid), poly (? -Hydroxyacid) Poly (3-hydroxyhexanoate, PHH), poly (4-hydroxyacid), poly (3-hydroxypropionate) (4-hydroxybutyrate), poly (4-hydroxyvalerate), poly (4-hydroxyhexanoate), poly (ester amide), polycaprolactone, polylactide, polyglycolide, poly (Glycolide-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane (polyglycolic acid), polyoxyethylene , Poly (amino acid), polycyanoacrylate, Poly (ethylene glycol), poly (trimethylene carbonate), poly (iminocarbonate), poly (tyrosine carbonate), polycarbonate, poly (tyrosine arylate), polyalkylene oxalate, polyphosphazene, PHA- (EVOH), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alpha olefin copolymers, styrene-isobutylene-styrene triblock copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers , Polyvinyl chloride, polyvinyl ether, polyvinyl methyl ether, polyvinylidene halide, polyvinylidene fluoride, polyvinylidene chloride, polyfluoroalkene, polyperfluoroalkene, polyacrylonitrile, polyvinyl ketone, Polyvinylaromatics, polystyrene, polyvinyl esters, polyvinyl acetate, ethylene-methyl methacrylate Acrylonitrile-styrene copolymers, ABS resins and ethylene-vinyl acetate copolymers, polyamides, alkyd resins, polyoxymethylene, polyimides, polyethers, polyacrylates, polymethacrylates, polyacrylic acid- (PHAs), poly (alpha -hydroxyapatite), polyglycerol, polyglycerol, polyglycerol, polyglycerol, Seed), poly (beta -hydroxyacid), poly (3-hydrobutyrate-co-valerate; PHB), poly (3-hydroxypropionate), poly (3-hydroxyhexanoate), poly (4-hydroxyacid) Poly (lactide-co-glycolide) (PLGA), poly (4-hydroxyhexanoate), poly (ester amide), polycaprolactone, polylactide, polyglycolide, (Polydioxanone), polyorthoesters, polyether esters, polyanhydrides, poly (glycolic acid-co-trimethylene carbonate), polyphosphoesters, polyphosphoester urethanes, poly (Polyacrylonitrile), polyalkylene oxalate, polyphosphazenes, PHA-PEG, chitosan, polyacrylonitrile, polyacrylonitrile, poly (trimethylene carbonate) Dextran, cellulo , Heparin, alginate, one desirable to use inulin, starch or glycogen, and the like.

Drugs may be further loaded within the gel base region.

As the drug, known drugs can be used. For example, the drug includes chemical drugs, protein drugs, peptide drugs, nucleic acid molecules for gene therapy and nanoparticles. Drugs that can be used in the present invention include, for example, anti-inflammatory agents, analgesics, antiarthritics, antispasmodics, antidepressants, antipsychotics, neurotransmitters, anxiolytics, drug antagonists, antiparkins disease drugs, cholinergic agonists, An anti-angiogenesis inhibitor, an immunosuppressant, an antiviral agent, an antibiotic, an appetite suppressant, an analgesic, an anticholinergic, an antihistamine, an anti-migraine agent, a hormone agent, a coronary blood vessel, a cerebrovascular or peripheral vasodilator, a contraceptive, Antihypertensive agents, therapeutic agents for cardiovascular diseases, cosmetic ingredients (e.g., anti-wrinkle agents, skin aging inhibitors and skin lightening agents), and the like.

The viscosity of the gel base region may be in the range of 5 Pa · s to 400 Pa · s at 25 ° C and is preferably 100 Pa · s to 400 Pa · s, but is not limited thereto. In this case, when the viscosity of the gel base region is less than the above range, it is difficult to form a uniform gel base region. When the viscosity of the gel base region exceeds the above range, There is a difficult problem.

The gel strength of the gel base region is preferably 0.03 N to 5 N, but is not limited thereto. When the gel strength of the gel base region is less than 0.03N, there is a problem that the gel base is broken at the time of insertion, and when the gel strength of the gel base region exceeds 5N, There is a problem of pain in insertion.

 The gel base region can be divided into multiple base regions, which can be classified according to the type of polymer substance (kind, weight average molecular weight, concentration, etc.) and the drug (type, concentration, etc.) will be.

Figure 3 is a view showing a gel base region formed in various diameters, various heights, and various shapes.

As shown in FIGS. 3 (a) to 3 (c), the diameter, height, and shape of the gel base region can be variously controlled according to a polymer material (kind, weight average molecular weight, concentration, etc.) The strength of the final microstructure, the degree of administration of the macromolecular substance or drug (the administration rate, the dose, and the depth of administration) can be variously adjusted. As shown in FIG. 3 (d), the gel base region may be a single base region, but the gel base region may be formed by different polymer materials (kind, weight average molecular weight, concentration, etc.) And then repeating the formation of the base region.

The formation of the gel base region may be performed by a method known in the art, and is preferably, but not limited to, performed by discharging, attaching, punching or molding.

Figure 4 is a diagram illustrating the formation of a gel base region by various methods.

As shown in Fig. 4, the formation of the gel base region can be performed by ejection, attachment or punching. Along with this, curing can occur.

On the other hand, a pre-coating layer may be formed on the support in advance.

The precoat layer may be formed in advance before forming the gel base region on the support wherein the precoat layer not only facilitates the separation of the gel base region from the support, , The skin penetration ability due to the improvement of the strength can be imparted, and the drug loading function can be given.

The precoat layer may be formed by a method known in the art, and is preferably formed by discharging, immersing and spraying, but is not limited thereto. Along with this, curing can occur.

FIG. 5 is a view showing a precoat layer of various materials. FIG.

As shown in FIG. 5, the precoat layer may include the same polymeric material as the polymeric material contained in the gel-like base region (FIG. 5), or may include a polymeric material different from the polymeric material contained in the gel- (Figure below).

The thickness of the precoat layer can be variously controlled according to the type of the polymer material (type, weight average molecular weight, concentration, etc.) included in the precoat layer, the forming method, and the like.

The method may further include modifying the gel base region concurrently with formation of the gel base region or after formation of the gel base region.

Deformation of the gel base region may be accomplished by cutting or drying. At this time, the concentration of the polymer substance in the gel-type base region can be further increased through drying.

6 is a view showing various modifications of the gel base region.

As shown in Fig. 6 (a), the gel base region can deform the shape of the gel-like base region through cutting, and the entirety of the gel base region can be deformed by the entire drying process, Dried), or the gel base region may be deformed by cutting, cutting, and drying after drying, as shown in FIG. 6 (c).

Next, a method of manufacturing a microstructure according to the present invention includes a step (b) of forming an outer region on the gel base region.

Formation of the outer region may be carried out through coating of the coating region comprising the second polymeric material on the gel base region or through attachment of the second microstructure onto the gel base region.

First, when the formation of the outer region is carried out through coating of a coating region comprising the second polymeric material on the gel base region, the coating region is formed on the gel base region, May be present in solution. That is, the weight average molecular weight of the second polymer material included in the coating region is lower than the weight average molecular weight of the polymer material contained in the gel base region.

Also, the viscosity of the outer region may be 0.15 Pa · s to 400 Pa · s at 25 ° C., and is preferably 0.15 Pa · s to 40 Pa · s, but is not limited thereto.

The second polymeric material may be a biocompatible or biodegradable material, and specific types of the biocompatible or biodegradable material are as described above.

That is, the second polymer material may be the same as or different from the above-mentioned polymer material.

In addition, the coating area may further include a drug, and the specific kind of the drug is also as mentioned above. The coating region may be formed such that the gel base region is entirely coated, or the gel base region may be partially coated.

In addition, the coating region can be divided into multiple coating regions, which can be classified according to the material (kind, weight average molecular weight, concentration, etc.) and the drug (kind, concentration, etc.) .

7 is a view showing a coating region formed in various shapes.

As shown in FIG. 7, the shape of the coating region can be variously controlled depending on the material (kind, weight average molecular weight, concentration, etc.), forming method, and the like, Accordingly, the strength, penetration, etc. of the finally fabricated microstructure can be variously adjusted. As shown in Fig. 7 (c), the coating region may be a single coating region, but the formation of the coating region is repeated by changing the material (kind, weight average molecular weight, concentration, etc.) and the loaded drug The coating may be divided into multiple coating areas.

After the coating, the coating region may be formed, or a separate microstructure may be deposited on the coating region.

At this time, the molding may be performed by one or more methods selected from the group consisting of molding, drawing, blowing, suction, centrifugal force application and magnetic field application by applying an exertion force to a coating area or a viscous droplet. Along with this, curing can occur.

8 is a view showing the molding of the coating region.

As shown in FIG. 8, the forming of the coating region in (c-1) may have various arrangements of the coating layer 30 'according to the molding method. According to various shapes and arrangements of the coating layer 30 ', strength, penetration, etc. of the microstructure to be finally produced can be controlled.

The present invention also provides a microstructure produced according to the above method.

In the case of microstructures prepared according to the above method, the strength is improved. In addition, when applied to human body, it is possible to administer a high-molecular-weight substance or drug in the human body.

The present invention also relates to a base material comprising a polymer material; And an outer layer comprising a second polymeric material formed on the base layer, wherein the second polymeric material has a weight average molecular weight or viscosity lower than that of the polymeric material.

The weight average molecular weight of the polymer material may be from 50 kDa to 2,500 kDa.

The viscosity of the polymeric material may be from 5 Pa · s to 400 Pa · s at 25 ° C.

The base layer is formed from a gel base region, and the outer layer is formed from an outer region, and the gel base region, the outer region, and a method of manufacturing the same are as described above.

The microstructure according to the present invention can be used in addition to a micro needle, a micro blade, a micro knife, a micro fiber, a micro spike, a micro probe, a microbarb, a microarray or a micro electrode.

Accordingly, in the case of the method for producing a microstructure using the gel polymer material according to the present invention, the use of the polymer material having a high weight average molecular weight facilitates the structure formation of the microstructure and improves the strength of the microstructure have. In addition, when applied to human body, it is possible to administer a high-molecular-weight substance or drug in the human body.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.

[ Example ]

Example  One

(1250 kDa) 25% (w / v)% gel was injected onto an aluminum column having a diameter of 190 탆 using a nozzle (MUSASHI engineering, SN-27G-LF) having an inner diameter of 190 탆 for 4 seconds at a speed of 100 탆 / The gel base area was formed by discharging and curing for 6.6 seconds, and then cut using a blade.

Thereafter, the viscosity of the discharged gel base region was measured using a Rheosys hardener (25 ° C, 30 mm Parallel Plate 1.0 mm Gap). As a result, it was confirmed that the gel base region was successfully manufactured at a viscosity of 203 Pa · s.

9A is an electron micrograph showing a gel base region formed according to Example 1. In FIG. 9A, the diameter of the gel base region is about 62.02 μm and the heights are about 394.12 μm and about 659.52 μm, respectively, It was confirmed that the gel base region was successfully fabricated.

40% (w / v)% solution of hyaluronic acid (30 kDa) was discharged onto the gel-type base region at 0.2 MPa for 0.22 sec using a dispenser (MUSASHI engineering, ML-5000XII) to form a coating area. Thereafter, the aluminum substrate on which the precoat layer had been previously formed was brought into contact with the top of the coating region, and then vertically drawn for 3.3 seconds at a speed of 100 占 퐉 / s. Thereafter, after curing for one minute, the microstructures were finally prepared by vertically raising the aluminum substrate on which the precoat layer had been previously formed at a rate of 100 mu m / s.

Then, the formed gel base region was measured for strength at a rate of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel base region was successfully manufactured at an average intensity of 1.3 N.

Example  2

(1250 kDa) 25% (w / v)% gel was sprayed on an aluminum column having a diameter of 190 탆 by using nozzles (MUSASHI engineering, SN-23G-LF and SN-20G-LF) having an inner diameter of 330 탆 and a diameter of 580 탆 The gel base area was formed by discharging and curing at a speed of 100 占 퐉 / s for 6 seconds and 6.5 seconds, and then cut using a blade. Thereafter, the microstructure was finally prepared in the same manner as in Example 1.

Thereafter, the viscosity of the discharged gel base region was measured using a Rheosys hardener (25 ° C, 30 mm Parallel Plate 1.0 mm Gap). As a result, it was confirmed that the gel base region was successfully manufactured at a viscosity of 203 Pa · s.

9 (b) is an electron micrograph showing the gel base region formed according to Example 2. In Fig. 9 (b), the gel base regions have diameters of about 341.37 탆 and about 575.54 탆, respectively, As a result, it was confirmed that the gel-type base region was successfully fabricated at about 444.44 탆.

Then, the formed gel base region was measured for strength at a rate of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel base region was successfully manufactured at an average intensity of 2.2 N.

Example  3

Carboxymethylcellulose (Sigma-Aldrich, Inc.) precoat layer 30 μm was previously formed on an aluminum substrate, and then hyaluronic acid (1250 kDa) 25 (w / v)% gel was applied. Subsequently, a nozzle (MUSASHI engineering, SN-27G-LF) having an inner diameter of 190 탆 was vertically lowered at a rate of 100 탆 / s to the applied hyaluronic acid gel, and the applied hyaluronic acid gel was mounted inside the nozzle. Subsequently, the nozzle equipped with the hyaluronic acid gel was placed at a height of 500 mu m on the aluminum substrate on which the precoat layer had been formed in advance, and was discharged at a pressure of 0.5 MPa using a dispenser (MUSASHI engineering, ML-5000XII) . Thereafter, the microstructure was finally prepared in the same manner as in Example 1.

Thereafter, the viscosity of the discharged gel base region was measured using a Rheosys hardener (25 ° C, 30 mm Parallel Plate 1.0 mm Gap). As a result, it was confirmed that the gel base region was successfully manufactured at a viscosity of 203 Pa · s.

Then, the formed gel base region was measured for strength at a rate of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel base region was successfully fabricated with an average intensity of 1.8 N.

9C is an electron micrograph showing the gel-type base region formed according to Example 3. In Fig. 9C, the diameter of the gel-type base region is about 218.64 mu m and about 196.11 mu m, respectively, and the height is about 368.34 mu m and It was confirmed that the gel-type base region was successfully manufactured at about 446.52 탆.

FIG. 9 (d) is an electron micrograph showing the microstructures finally prepared according to Example 3, confirming that microstructures were successfully produced.

Example  4

After precoating 30 m of carboxymethylcellulose (Sigma-Aldrich, Inc.) precoat layer on an aluminum substrate, a gel of hyaluronic acid (800 kDa) 10 (w / v) TPND-25G). Then, the nozzle equipped with the hyaluronic acid gel was placed at a height of 100 mu m on the aluminum substrate on which the precoat layer had been formed in advance, and was discharged at a pressure of 0.2 MPa using a dispenser (MUSASHI engineering, ML-5000XII). Thereafter, the viscosity of the discharged gel base region was measured using a Rheosys hardener (25 ° C, 30 mm Parallel Plate 1.0 mm Gap). As a result, it was confirmed that the gel base region was successfully produced at a viscosity of 180 Pa · s.

Then, a carboxymethyl cellulose precoat layer was attached to a height of 1.0 mm, and the mixture was dried for 5 minutes and separated to prepare a gel-type base region.

55% (w / v)% solution of hyaluronic acid (39 kDa) was discharged onto the gel-type base region with a dispenser (MUSASHI engineering, ML-5000II) at a pressure of 0.2 MPa for 0.22 seconds to form a coating region. Thereafter, the gel base region on which the coating region was formed was mounted on a centrifuge (Hanil, Combi 514-R), and then the aluminum substrate on which the precoat layer had been formed was placed at 1.0 mm intervals from the gel base region where the coating region was formed. Thereafter, after rotating for 60 seconds at a speed of 2000 rpm, the microstructure was finally prepared after curing for 1 minute.

Then, the formed gel base region was measured for strength at a rate of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel base region was successfully manufactured at an average intensity of 1.5 N.

10 (a) is an electron micrograph showing the gel-type base region formed according to Example 4. In FIG. 10 (a), the gel-type base region has a diameter of about 557.69 μm and a height of about 365.38 μm, Was successfully fabricated.

10 (b) and 10 (c) are electron micrographs showing the microstructures finally prepared according to Example 4, confirming that microstructures were successfully produced.

Example  5

Carboxymethylcellulose (Sigma-Aldrich, Inc.) precoat layer 30 μm was previously formed on an aluminum substrate, and then 10% (w / v) gel of hyaluronic acid 1400 kDa (MUSASHI engineering, TPND-25G). Then, the nozzle equipped with the hyaluronic acid gel was placed at a height of 100 mu m on the aluminum substrate on which the precoat layer had been formed in advance, and was discharged at a pressure of 0.2 MPa using a dispenser (MUSASHI engineering, ML-5000XII). Thereafter, the viscosity of the discharged gel base region was measured using a Rheosys hardener (25 ° C, 30 mm Parallel Plate 1.0 mm Gap). As a result, it was confirmed that the gel base region was successfully manufactured at a viscosity of 193 Pa · s.

Then, a carboxymethyl cellulose precoat layer was attached to a height of 1.0 mm, and the mixture was dried for 5 minutes and separated to prepare a gel-type base region.

Thereafter, the microstructure was finally prepared in the same manner as in Example 4.

Then, the formed gel base region was measured for strength at a rate of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel base region was successfully manufactured at an average intensity of 1.5 N.

11 (a) is an electron micrograph showing the gel base region formed according to Example 5. In Fig. 11 (a), the gel base region has a diameter of about 324.74 占 퐉 and a height of about 247.77 占 퐉, Was successfully fabricated.

FIG. 11 (b) is an electron micrograph showing the microstructure finally produced according to Example 5, and it can be confirmed that the microstructure was successfully manufactured.

Example  6

A gel-type base region was prepared in the same manner as in Example 5. At this time, the viscosity of the discharged gel base region was measured using a Rheosys hardener (25 ° C, 30 mm Parallel Plate 1.0 mm Gap). As a result, it was confirmed that the gel base region was successfully manufactured at a viscosity of 193 Pa · s.

55% (w / v)% solution of hyaluronic acid (39 kDa) was dispensed onto the gel-type base region using a dispenser (MUSASHI engineering, ML-5000II) at a pressure of 0.2 MPa for 0.40 seconds to form a coating area. Thereafter, the gel base region on which the coating region was formed was mounted on a centrifuge (Hanil, Combi 514-R), and then the aluminum substrate on which the precoat layer had been formed was placed at 1.0 mm intervals from the gel base region where the coating region was formed. Thereafter, after rotating for 60 seconds at a speed of 2000 rpm, the microstructure was finally prepared after curing for 1 minute.

Then, the formed gel base region was measured for strength at a rate of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel base region was successfully manufactured at an average intensity of 1.5 N.

Figures 12 (a) and 12 (b) are electron micrographs showing microstructures prepared according to Example 6, wherein the gel base regions have diameters of about 485 占 퐉 and about 610 占 퐉, respectively, About 317 mu m, and the height of the microstructure was 461 mu m and about 495 mu m, respectively, and it was confirmed that the microstructure was successfully manufactured.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.

Claims (19)

(a) forming a gel-type base region comprising a polymeric material on a support; And
(b) forming an outer region on the gel base region
A method of manufacturing a microstructure.
The method according to claim 1,
In the above (a), the weight average molecular weight of the polymer substance is from 50 kDa to 2,500 kDa
A method of manufacturing a microstructure.
The method according to claim 1,
In (a), the viscosity of the gel base region is from 5 Pa · s to 400 Pa · s at 25 ° C.
A method of manufacturing a microstructure.
The method according to claim 1,
In the step (a), the gel strength of the gel base region is 0.03 N to 5 N
A method of manufacturing a microstructure.
The method according to claim 1,
In the step (a), the gel base region is divided into multiple base regions
A method of manufacturing a microstructure.
The method according to claim 1,
In the step (a), in the gel-type base region or in the step (b)
A method of manufacturing a microstructure.
The method according to claim 1,
In the step (a), the formation of the gel-like base region is performed by discharging, attaching, punching or molding
A method of manufacturing a microstructure.
The method according to claim 1,
A pre-coating layer is formed on the support in advance
A method of manufacturing a microstructure.
The method according to claim 1,
Further comprising the step of modifying the gel base region at the same time as the formation of the gel base region in the step (a), or after the formation of the gel base region in the step (a)
A method of manufacturing a microstructure.
The method according to claim 1,
In the step (b), formation of the outer region is performed through coating of the coating region including the second polymer material on the gel base region,
Wherein the second polymeric material has a smaller weight average molecular weight or viscosity than the polymeric material
A method of manufacturing a microstructure.
The method according to claim 1,
In the step (b), formation of the outer region is performed through attachment of the second micro-structure on the gel-like base region
A method of manufacturing a microstructure.
11. The method of claim 10,
The coating area is divided into multiple coating areas
A method of manufacturing a microstructure.
11. The method of claim 10,
The coating is applied by ejection, immersion or spraying
A method of manufacturing a microstructure.
11. The method of claim 10,
After the coating, the coating area is formed, or a separate microstructure is attached on the coating area
A method of manufacturing a microstructure.
15. The method of claim 14,
The molding is performed in one or more methods selected from the group consisting of molding, drawing, blowing, suction, centrifugal force application and magnetic field application
A method of manufacturing a microstructure.
A microstructure produced according to the method of claim 1.
A base layer comprising a polymeric material; And
And an outer layer comprising a second polymeric material formed on the base layer,
Wherein the second polymeric material has a smaller weight average molecular weight or viscosity than the polymeric material
Microstructures.
18. The method of claim 17,
The weight average molecular weight of the polymeric material is in the range of 50 kDa to 2,500 kDa
Microstructures.
18. The method of claim 17,
The viscosity of the polymeric material ranges from 5 Pa · s to 400 Pa · s at 25 ° C.
Microstructures.

Images