KR102249513B1 - A candle-typed microstructure for transdermal delivery and a method for manufacturing the same - Google Patents

Abstract

A candle-type microstructure and a method of manufacturing the same are provided. The method of manufacturing a candle-type microstructure of the present invention comprises the steps of: (a) placing a first viscous composition on a substrate; (b) molding the first viscous composition; (c) placing a second viscous composition on the molded first viscous composition; And (d) stretching the first viscous composition and the second viscous composition by centrifugal force. Here, (b) forming the first viscous composition includes forming a lower portion of the body portion, the neck portion, and the head portion on the substrate, and (b-1) placing the upper plate on the upper portion of the substrate; (b-2) contacting the first viscous material with the upper plate; And (b-3) comprising the step of removing the upper plate, (d) the step of stretching the second viscous composition is to increase the extension length of the candle-type microstructure including the first viscous composition and the second viscous composition than the previous step. It is formed long, and the end of the head part is sharply extended.

Description

Candle-type microstructure and its manufacturing method {A candle-typed microstructure for transdermal delivery and a method for manufacturing the same}

The present invention relates to a candle-type microstructure and a method of manufacturing the same. In more detail, it relates to a candle-type microstructure that can be used for transdermal delivery and a method of manufacturing the same.

Numerous drugs and therapeutics have been developed for the treatment of diseases, but in delivering drugs into the body, problems with passage of biological barriers (e.g., skin, oral mucosa, and brain-vascular barriers) and efficiency of drug delivery Remains to be improved.

Drugs are generally administered orally in tablet form or capsule form, but for reasons such as digestion or absorption in the gastrointestinal tract or loss by the mechanism of the liver, such drugs cannot be effectively delivered by the above administration method alone. In addition, some drugs cannot effectively diffuse through the intestinal mucosa. In addition, patient compliance is also an issue (for example, in critically ill patients who have to take medication at certain intervals or cannot take medication).

Another common technique for drug delivery is the use of a conventional needle. While this method is effective compared to oral administration, there are problems of causing pain at the injection site, local damage to the skin, bleeding, and disease infection at the injection site.

In order to solve the above problems, various microstructures including microneedles have been developed. Microstructures developed to date have been mainly used for drug delivery in vivo, blood collection, and detection of analytes in the body.

Existing biodegradable microstructures or microstructures required a separate adhesive sheet to adhere to the skin and fix it for a long time. Due to the use of the adhesive sheet, the user may feel a foreign body, and an allergic reaction may occur. In addition, there is a problem that there is a limitation in application to the joints where movement is severe, skin with curves, and skin with hair.

In addition, when applying the patch to the skin, in order to effectively penetrate the microstructure into the skin, it is pressed with a finger. In some cases, a difference in the pressing force occurs, and because the force is not evenly distributed over the penetration area with the finger, there is a problem of penetration. There is.

In addition, even if all the microstructures on the same array have completely penetrated into the skin, it takes several minutes to several hours for the polymer matrix to be completely dissolved in the skin, depending on the type of the polymer, and during this time, the user feels uncomfortable.

In order to solve this problem, the need for microstructures in which the microstructures penetrating into the skin are completely fixed without being separated from the base and capable of accurate drug delivery is possible, and the need for microstructures in which the parts penetrating the skin can be easily separated from the base is increasing.

KR 2014-0131879 A

According to an embodiment of the present invention, it is intended to provide a candle-type microstructure and a method of manufacturing a candle-type microstructure that are firmly inserted into the skin to enable accurate drug delivery and are not separated from the skin by an external force.

According to an aspect of the present invention, a body portion formed on a substrate and having a first cross-section; The body portion includes a second cross-section smaller than the first cross-section, and includes a neck portion formed on the body portion so as to extend in a direction away from the substrate, and a third cross-section wider than the second cross-section of the neck portion, and the substrate And a head portion formed on the neck portion so as to extend in a direction away from the head portion, and the third end face of the head portion has a cross section that is wider than an end surface of the neck portion far from the substrate, and when viewed in a direction away from the substrate, the head portion It is the widest cross section among the cross-sections, and the head part is implanted into the skin while the third cross-section is inserted into the skin, and 60 to 90% of the total volume is in the range of 60% of the total height from the tip of the head part. A method for manufacturing a candle-type microstructure comprising a continuous curved surface in a direction away from the substrate in which the outer surface of the body part, the neck part, and the head part so as to have a volume, comprising the steps of: (a) placing a first viscous composition on a substrate ; (b) stretching the first viscous composition; (c) placing a second viscous composition on the stretched first viscous composition; And (d) stretching the first viscous composition and the second viscous composition by an additional centrifugal force; and (b) stretching the first viscous composition includes a body part, a neck part, and a Forming a lower portion of the head, and (b-1) placing an upper plate on the substrate; (b-2) applying a centrifugal force to the first viscous composition to bring the first viscous material into contact with the upper plate; And (b-3) removing the upper plate, and (d) stretching the second viscous composition includes the extension length of the candle-type microstructure including the first viscous composition and the second viscous composition. There is provided a method of manufacturing a candle-type microstructure in which is formed longer than the previous step and sharply extends the end of the head portion.

In this case, positioning the second viscous composition on the stretched first viscous composition may include applying or dropping the second viscous composition on the first viscous composition.

According to another aspect of the present invention, (a) placing a first viscous composition on a substrate; (b) molding the first viscous composition; (c) placing a second viscous composition on the molded first viscous composition; And (d) stretching the first viscous composition and the second viscous composition by a centrifugal force; and, (b) forming the first viscous composition includes a body part, a neck part, and a head on the substrate. Forming a lower portion of the negative, and (b-1) placing an upper plate on the upper portion of the substrate; (b-2) contacting the first viscous material with the upper plate; And (b-3) removing the upper plate, and (d) stretching the second viscous composition includes the extension length of the candle-type microstructure including the first viscous composition and the second viscous composition. There is provided a method of manufacturing a candle-type microstructure in which is formed longer than the previous step and sharply extends the end of the head portion.

According to another aspect of the present invention, there is provided a candle-type microstructure manufactured according to the manufacturing method as described above.

In this case, the neck portion may be physically or chemically cut while the head portion and a portion of the neck portion of the candle-type microstructure are inserted into the skin, so that the head portion may be implanted into the skin.

In this case, the force to physically cut the neck portion may be a force that presses the neck portion in a transverse direction with respect to the extension direction of the neck portion while the head portion is inserted into the skin.

In this case, the force pressing the neck portion may be provided from a driving portion for moving the substrate in the transverse direction.

In this case, the body portion, the neck portion, and the head portion may be integrally formed.

In this case, the neck portion and the head portion may be formed of different materials.

In this case, the body part, the neck part, and the head part may be filled in the inside.

In this case, when a force is applied from the end of the microstructure, while the microstructure is collapsed, as the displacement applied to the force increases, the resistance force may increase and then decrease at two or more inflection points.

In the candle-type microstructure according to an exemplary embodiment of the present invention, when the skin is inserted, the cross-section of the head inserted into the body is wider than the cross-sectional area of the neck, so that the neck of the candle-type microstructure is physically or chemically cut. The large volume of the head part can be maintained in the skin so that many drugs can be delivered into the skin.

In addition, in the candle-type microstructure according to an exemplary embodiment of the present invention, when the skin is inserted, the cross-section of the head inserted into the body is wider than the cross-sectional area of the neck, so that the neck of the candle-type microstructure is physically or chemically cut. The large volume of the head portion can be maintained in the skin in the condition that the head portion is inserted into the skin, so that the head portion can be well fixed to the skin without being removed.

The candle-type microstructure according to an exemplary embodiment of the present invention can determine various skin injection depths by adjusting the length, width, and cross-sectional area of the head, neck, and body, and the amount of drug administered can be adjusted. It is possible to provide a microstructure of the form.

A substrate or patch having a candle-type microstructure according to an exemplary embodiment of the present invention separates the substrate, patch, or film from the microstructure with a predetermined force after the microstructure is embedded in the skin. Since it is not provided, it has the advantage of being easy to use, and due to the curved shape and the candle structure having a neck part, the effect of reducing skin damage that occurs during skin penetration and speeding up the recovery speed is obtained.

1 is a cross-sectional view of a candle-type microstructure according to an embodiment of the present invention.
2 is a diagram showing numerical values of a candle-type microstructure according to an embodiment of the present invention.
3 is a diagram showing a manufacturing process of a candle-type microstructure according to an embodiment of the present invention.
4 is a case in which the candle-type microstructure according to an embodiment of the present invention is formed of an HA material (a), when formed of a Rhodamine material (b), a neck portion is formed of an HA material, and a head portion is formed of a Rhodamine material. This is a picture showing case (c).
5 is a diagram illustrating a process of physically cutting a candle-type microstructure according to an embodiment of the present invention after being inserted into the skin.
6 is a view showing a process of chemically cutting after inserting a candle-type microstructure according to an embodiment of the present invention into the skin.
7 is a diagram illustrating a state in which a candle-type microstructure according to an embodiment of the present invention is inserted into the skin at different depths.
8 is a diagram illustrating a case in which a candle-type microstructure according to an embodiment of the present invention is inserted into the skin and a case where a conventional microstructure is inserted into the skin in order to compare the amount of drug delivery.
9 is a diagram for comparing the distribution of drugs in a longitudinal direction between a candle-type microstructure and a conventional microstructure according to an embodiment of the present invention.
10 is a diagram illustrating a degree of easy skin separation when a candle-type microstructure according to an embodiment of the present invention is inserted into the skin and when a conventional microstructure is inserted into the skin.
FIG. 11 is a photograph experimentally showing FIG. 10, and the degree of ease of skin separation is experimentally examined when the candle-type microstructure according to an embodiment of the present invention is inserted into the skin and when the conventional microstructure is inserted into the skin. This is a picture showing.
FIG. 12 is a diagram illustrating a resistance force according to a displacement applied when a force is applied when each of the microstructures collapses when a force is applied from the end of the candle-type microstructure (a) and the conventional microstructure (b) according to an embodiment of the present invention. This is a graph comparing the size change.
13 is a graph showing a ratio of a microstructure according to an embodiment of the present invention and a drug contained in a conventional microstructure according to an embodiment of the present invention are administered to the skin over time.
14 is a photograph showing a comparison of the amount of material remaining on the substrate after a predetermined period of time after the microstructure (a) according to an embodiment of the present invention and the conventional microstructure (b) are injected into the skin.
15 is a photograph for comparing a microstructure and a conventional microstructure according to an embodiment of the present invention,
(1) is a picture taken with the microstructure formed,
(2) is a plan view of the state in which the drug was injected on the skin after 0 hours, 10 minutes, and 30 minutes after being in contact with the skin,
(3) is a cross-sectional picture of the drug administered inside the skin.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those of ordinary skill in the art may easily implement the present invention. The present invention may be implemented in various different forms and is not limited to the embodiments described herein. In the drawings, parts irrelevant to the description are omitted in order to clearly describe the present invention, and the same reference numerals are assigned to the same or similar components throughout the specification.

In the present specification, terms such as "comprise" or "have" are intended to designate the presence of features, numbers, steps, actions, components, parts, or a combination thereof described in the specification, but one or more other features. It is to be understood that the presence or addition of elements or numbers, steps, actions, components, parts, or combinations thereof, does not preclude in advance the possibility of the presence or addition.

1 is a cross-sectional view of a candle-type microstructure according to an embodiment of the present invention. 2 is a diagram showing numerical values of a candle-type microstructure according to an embodiment of the present invention.

1 and 2, the candle-type microstructure 10 according to an embodiment of the present invention may include a body portion 20, a neck portion 30, and a head portion 40.

Referring to FIG. 1, a candle-type microstructure may be formed on a substrate 2.

As shown in FIG. 1, the body portion 20 is positioned on the substrate 2, and the neck portion 30 and the head portion 40 are on the body portion 20 in a direction away from the substrate (z-axis direction). It is arranged to extend.

In one embodiment of the present invention, the body portion 20, the neck portion 30, and the head portion 40 forming the candle-type microstructure 10 are integrally formed using the same material or formed of different materials. I can.

According to an embodiment of the present invention, the material forming the candle-type microstructure 10 used in the present invention includes a biocompatible or biodegradable material. In the present specification, the term "biocompatible substance" refers to a substance that is substantially non-toxic to the human body, is chemically inactive, and is not immunogenic. In the present specification, the term “biodegradable material” refers to a material that can be degraded by body fluids or microorganisms in a living body.

Specifically, biocompatible and/or biodegradable materials that can be used in the present invention are, for example, polyester, polyhydroxyalkanoate (PHAs), poly(α-hydroxyacid), poly(β- Hydroxyacid), poly(3-hydrosicbutyrate-co-valerate; PHBV), poly(3-hydroxypropionate; PHP), poly(3-hydroxyhexanoate; PHH), poly (4-hydroxyacid), poly(4-hydroxybutyrate), poly(4-hydroxyvalerate), poly(4-hydroxyhexanoate), poly(esteramide), polycaprolactone, poly Lactide, polyglycolide, poly(lactide-co-glycolide; PLGA), polydioxanone, polyorthoester, polyetherester, polyanhydride, poly(glycolic acid-co-trimethylene carbonate), Polyphosphoester, polyphosphoester urethane, poly(amino acid), polycyanoacrylate, poly(trimethylene carbonate), poly(iminocarbonate), poly(tyrosine carbonate), polycarbonate, poly(tyrosine arylate) ), polyalkylene oxalate, polyphosphazens, PHA-PEG, ethylene vinyl alcohol copolymer (EVOH), polyurethane, silicone, polyester, polyolefin, polyisobutylene and ethylene-alphaolefin copolymer, 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, polyvinyl aromatics, polystyrene, polyvinyl ester, polyvinyl acetate, ethylene-methyl methacrylate copolymer, acrylonitrile- Styrene copolymer, ABS resin and ethylene-vinyl acetate copolymer, polyamide, alkyd resin, polyoxymethylene, polyimide, polyether, polyacrylate, polymethacrylate, polyacrylic acid-co-maleic acid, chitosan, dex Tran, cellulose , Heparin, hyaluronic acid, alginate, inulin, starch or glycogen, preferably polyester, polyhydroxyalkanoate (PHAs), poly(α-hydroxy acid), poly(β-hydroxy acid) ), poly(3-hydrosoxybutyrate-co-valerate; PHBV), poly(3-hydroxypropionate; PHP), poly(3-hydroxyhexanoate; PHH), poly(4-hydroxyacid), poly(4-hydroxybutyrate), poly (4-hydroxyvalerate), poly(4-hydroxyhexanoate), poly(esteramide), polycaprolactone, polylactide, polyglycolide, poly(lactide-co-glycolide; PLGA) , Polydioxanone, polyorthoester, polyetherester, polyanhydride, poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acid), Polycyanoacrylate, poly(trimethylene carbonate), poly(iminocarbonate), poly(tyrosine carbonate), polycarbonate, poly(tyrosine arylate), polyalkylene oxalate, polyphosphazene, PHA-PEG , Chitosan, dextran, cellulose, heparin, hyaluronic acid, alginate, inulin, starch or glycogen.

In this case, according to an embodiment of the present invention, the body portion 20 may be formed in a cylindrical shape having a circular cross section. In this embodiment, the body portion 20 has a first cross-section in contact with the substrate, and the first cross-section, that is, a length L1 of the diameter of the body portion in contact with the substrate may be 10 to 1,000 μm. However, the length of the diameter of the body portion 20 is not limited thereto.

In an embodiment of the present invention, the body portion 20 may be formed such that the area of the cross-section becomes narrower toward a direction away from the substrate 2. The extending length H1 of the body 20 in a direction away from the substrate 2 may be 10 to 500 μm, but is not limited thereto. The upper surface of the body portion 20 may have a cross-section smaller than the first end surface of the body portion, and in this case, the diameter L4 of the cross-section of the upper surface of the body portion may be 5 to 750 μm.

Referring to FIGS. 1 and 2, when viewed in FIG. 1, a neck portion 30 is positioned on an upper portion of the body portion 20, that is, at an end portion of the body portion 20 in a direction away from the substrate 2.

The neck portion 30 may be formed to extend continuously or discontinuously from the upper surface of the body portion 20, and may include a second cross-section smaller than the first cross-section of the body portion 20. The neck portion 30 may be formed in a cylindrical shape having a circular cross section.

In an embodiment of the present invention, the neck portion 30 may be formed to have a cross section of the narrowest area at the central portion of the neck portion 30 when viewed in a direction away from the substrate. In the present embodiment, a cross-section of the narrowest area among the cross-sections of the neck portion, which is located at the center portion of the neck portion, is defined as the second cross-section.

In one embodiment of the present invention, the diameter L2 of the second cross section may be 5 to 500 μm.

In this embodiment, the neck portion 30 may be made symmetrically around the second cross-section when viewed in the extending direction of the neck portion 30, and such a shape is obtained by tensioning the neck portion 30 by centrifugal force or the like, as described later. It may be a form that is formed.

Meanwhile, the extension length H4 from the substrate 2 to the second end face of the neck portion 30 may be 50 to 1,000 um, and the extension length H2 of the neck portion may be 50 to 1,000 um.

In this embodiment, the length of the top surface of the neck portion 30 is L5, and may be formed equal to the length of L4, and the head portion 40 may be formed thereon. The head portion 40 may be connected to the neck portion 30 continuously or discontinuously, and may be formed in a column shape having a circular cross section extending from the neck portion 30.

The head portion 40 has a third cross-section having a larger area than the second cross-section of the neck portion 30. In this embodiment, the third cross-section may be defined as a cross-section having the largest area among cross-sections forming the head portion. In this embodiment, the diameter L3 of the third cross section may be 100 to 500 μm. In this case, the distance H5 from the substrate to the third end surface may be 100 to 1,000 μm, and the distance H6 from the third end surface to the tip of the head may be 100 to 1,000 μm. In addition, the extension length (H3) of the body portion may be 100 ~ 1,000um.

Accordingly, the head portion 40 has a cross section that is wider in the extending direction from the bottom having a narrower cross-section than the third cross-section, and has the widest cross-section in the third cross-section. It is formed to be narrow in width, and is formed to be finished in a sharp shape at one end in the extending direction of the head portion.

In one embodiment of the present invention, the head portion 40 is a first volume region 42 located at a first extension length from one end of the neck portion 30 to the third end face in a direction away from the substrate 2 , A second volume region 44 positioned at an extension length equal to twice the first extension length from the third cross-section and a third volume region 46 positioned above the second volume region. The length of the top surface of the second volume region is L6. L6 may be less than or equal to L5. In this case, the combined volume of the first volume region 42 and the second volume region 44 may be 2 to 1000 times the volume of the third volume region 46. In addition, the head portion may have a volume of 1.5 to 100 times the volume of the body portion and the neck portion. In this embodiment, the head portion 40 may be a portion containing a drug that is injected into the skin while the microstructure 10 is inserted into the skin. The amount of medication that can be increased can be high.

Accordingly, the microstructure according to an embodiment of the present invention including the body portion 20, the neck portion 30, and the head portion 40 is formed to form a candle shape as a whole. In the present specification, such a candle-shaped microstructure is defined as a candle-type microstructure. In this case, in the present embodiment, it is illustrated that the body part 20, the neck part 30, and the head part 40 form a candle shape as a whole, but the shape of the microstructure of the present invention is not limited thereto.

In this case, the outer surfaces of the body portion 20, the neck portion 30, and the head portion 40 may be formed as a continuous curved surface in a direction away from the substrate 2. However, according to the manufacturing process of the body portion 20, the neck portion 30, and the head portion 40, the body portion 20, the neck portion 30, and the head portion 40 may be formed to have a discontinuous surface.

In this case, the total length of extension from the substrate 2 to the tip of the head of the microstructure may be 200 to 2,000 μm, but is not limited thereto.

The microstructure 10 according to an embodiment of the present invention may be formed in a form filled with the inside, and may be formed to contain a drug for administration to the skin therein.

In describing the microstructure according to the present embodiment, the microstructure is divided into a body portion, a neck portion, and a head portion, and the length of one cross section of the body portion, the neck portion, and the head portion is exemplarily described, but the microstructure is a single material. When manufactured and integrally formed, the body portion, the neck portion, and the head portion may not be clearly partitioned, and those skilled in the art will readily understand that the length of each cross-section described in the present embodiment is exemplary. Also, depending on the manufacturing process, the body portion may not be formed in the microstructure.

A process for manufacturing a microstructure configured as described above is shown in FIG. 3.

Referring to FIG. 3, in a method of manufacturing a candle-type microstructure according to an embodiment of the present invention, a first viscous composition 1 is placed on a substrate 2 as a first process. (3(a)) Positioning the first viscous composition 1 on the substrate may be achieved through a dropping (dropping) process. In this case, the viscous composition 1 may be formed by a biocompatible or biodegradable material as described above, or a drug that can be injected into the body, and a combination thereof.

Thereafter, the first viscous composition 1 is stretched in a direction away from the substrate. (3(b)) At this time, stretching the first viscous composition (1) may be performed using a centrifugal force (F1).

In this way, before the first viscous composition 1 is stretched using a centrifugal force, as shown in FIG. 3, the upper plate 4 is placed on the upper portion of the substrate 2 in the tensile direction of the first viscous composition 1, 1 When a tensile force is applied to the viscous composition (1), the end of the first viscous composition (1) is in contact with one surface of the top plate (4) as the first viscous composition (1) is stretched.

As described above, when the first viscous composition 1 contacts one surface of the top plate 4, the body portion 20 and the neck portion 30, and the head portion 40 of the candle-type microstructure according to an embodiment of the present invention The lower part of is formed by the first viscous composition (1). After that, the top plate 4 is removed, and the second viscous composition 3 is placed on the first viscous composition 1. (Fig. 3(d))

In this case, the second viscous composition (3) may be the same composition as the first viscous composition (1) or may be a different composition. 4 shows a case in which the first and second viscous compositions of the candle-type microstructure according to an embodiment of the present invention are formed of an HA material (a), and the first and second viscous compositions are formed of a Rhodamine material. (b), a photograph showing a case (c) is shown in which the body part and the neck part are formed of HA material using the first viscous composition and the second viscous composition is formed of Rhodamine material.

The second viscous composition may be placed on the first viscous composition (1) by application or dropping (dropping) method, with the second viscous composition (3) placed on the first viscous composition (1) Tensile force, for example, a centrifugal force is applied (FIG. 3(e)) to form a longer extension length of the microstructure comprising the first viscous composition 1 and the second viscous composition 3, and to make the end of the head part Can be elongated sharply. (FIG. 3(f))

In this embodiment, the process of manufacturing the candle-type microstructure was described by placing the second viscous composition (3) on top of the first viscous composition (1), but the process of manufacturing the candle-type microstructure was described. The present invention is not limited thereto, and a candle-type microstructure may be manufactured through various known processes.

Features of the candle-type microstructure formed by the above process will be described with reference to the drawings.

5 is a diagram illustrating a process of physically cutting a candle-type microstructure according to an embodiment of the present invention after being inserted into the skin. 6 is a view showing a process of chemically cutting after inserting a candle-type microstructure according to an embodiment of the present invention into the skin.

5A to 5C and 6A to 6C, the candle-type microstructure according to an embodiment of the present invention includes a head portion 40 and a portion of the neck portion 30. While the is inserted into the skin, one side of the neck part 30 may be physically or chemically cut so that the head part may be positioned in the skin.

In this case, as an embodiment, the force to physically cut the neck portion may be a force (F2) that presses the neck portion in a transverse direction or a longitudinal direction with respect to the extension direction of the neck portion while the head portion is inserted into the skin. In this case, the force F2 for pressing the neck portion in the transverse or longitudinal direction may be applied to the substrate, or may be applied to the body portion 20 or one end side of the neck portion 30 adjacent to the substrate 2.

When the force F2 cutting the neck portion 30 is physically applied to the neck portion, the neck portion may be broken at the second cross-section having the narrowest cross-section at the neck portion, or the neck portion may be cut at other positions.

In this case, a separate driver may be provided to apply a force to the substrate 2 as described above, or a predetermined cutting knife may be provided to cut the neck portion 30 in the transverse direction. The magnitude of the force applied to cut the neck portion 30 may be selectively made according to the shape, material, and size of the microstructure 10.

Meanwhile, referring to FIG. 6, in order to chemically cut the neck portion 30, a chemical substance 6 capable of causing a chemical reaction with a material constituting the neck portion may be provided. Such a chemical substance may be experimentally selected depending on the material constituting the neck part 30.

For example, an aqueous solution containing water, an anhydrous or aqueous lower alcohol having 1-4 carbon atoms, acetone, ethyl acetate, chloroform, 1,3-butylene glycol, hexane, diethyl ether or butyl acetate, a water-insoluble agent, propylene glycol, Polyethylene glycol, oily ingredients, injectable esters such as ethyl oleate, etc. can be used. In addition, as an oil that can be mainly used as an oily component, at least one selected from vegetable oils, mineral oils, silicone oils, and synthetic oils may be used. More specifically, mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitis vinifera seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, dime Chicon, cyclopentasiloxane, and sunflower seed oil can be used.

As described above, in the candle-type microstructure 10 according to an embodiment of the present invention, a part of the neck part 30 is physically or chemically applied in a state in which a part of the head part 40 and the neck part 30 are inserted into the skin. Since the neck portion 30 is cut, the head portion 40 and the neck portion 30 of the candle-type microstructure 10 can be held firmly in position in the skin even after the neck portion 30 is cut, while the neck portion 30 is being cut. It may not fall outside the skin.

7 is a diagram illustrating a state in which a candle-type microstructure according to an embodiment of the present invention is inserted into the skin at different depths to be inserted into the skin.

Referring to FIGS. 7A to 7C, the candle-type microstructure according to an embodiment of the present invention has the strength to insert the type of the drug solution inserted into the skin and the depth of the inner skin layer to which the drug is to be administered. The insertion depth of the candle-type microstructure inserted into the skin may be varied depending on the size and the like. For example, the magnitude of the force may be 0.001 N or more.

Figure 7 (a) is a case in which the deepest microstructure is inserted, and in the order of (b) and (c) of Figure 7 is a case in which a shallow depth is inserted. Even in the case where the microstructure is inserted into the skin at various depths (Hs) as described above, the microstructure 10 should have the third cross-sectional portion having the widest cross-section of the head portion 40 disposed at a position deeper than the epidermal layer of the skin. There is a need.

If the third cross-sectional portion having the widest cross-section of the head portion 40 passes through the epidermal layer of the skin and does not enter the skin, the microstructure 10 cannot be embedded in the skin due to the elasticity of the skin and It can be deviated outward.

In the microstructure 10 according to an embodiment of the present invention, the substrate on which the candle-type microstructure 10 is formed is pressed against the skin so that the portion having the widest cross-section of the microstructure, that is, the head portion, is inserted into the skin. By breaking the neck of the micro-structure 10, the micro-structure can be positioned inside the skin.

At this time, in the candle-type microstructure 10 according to an embodiment of the present invention, the neck portion 30 is moved in a transverse direction to remove the substrate while the head of the microstructure is inserted in the skin in a direction perpendicular to the skin. It is configured to break, and since the substrate 2 can be removed immediately while the head portion 40 is inserted in a direction perpendicular to the skin, it is possible to implant the chemicals contained in the conventional microstructure microstructure into the skin for a long time. Time Microstructure Compared with maintaining a state in which the substrate on which the microstructure is formed in contact with the skin, the time required for maintaining the state in which the substrate on which the microstructure is formed is in contact with the skin is significantly shortened, which has the advantage of being easy to use.

8A and 8B are diagrams illustrating a case in which a candle-type microstructure according to an embodiment of the present invention is inserted into the skin and a case where a conventional microstructure is inserted into the skin to compare the amount of drug delivery. to be. 9 is a view for comparing the distribution of drugs in the height direction of the candle-type microstructure and the conventional microstructure according to an embodiment of the present invention, FIG. 9A is a height direction to compare the distribution of drugs in the length direction. It is a diagram showing the ratio of drugs contained in each division area after being divided into five, and FIG. 9B is a ratio in which the microstructure according to an embodiment of the present invention and the drug contained in the conventional microstructure are contained according to the height of the microstructure. It is a graph showing the accumulation of (%).

Referring to FIGS. 8A and 8B and FIGS. 9A and 9B, a candle-type microstructure 10 according to an embodiment of the present invention is a conventional microstructure of a pointed triangular shape. Compared to 100, a larger amount of drugs can be stored in the head portion 40 of the microstructure than in the conventional microstructure. This is according to the shape characteristic of the head portion of the candle-type microstructure 10 according to an embodiment of the present invention. As can be seen in (a) and (b) of FIG. 9, only about 31% of drugs can be contained in the height range of the upper 60% corresponding to the head part in the height direction of the conventional microstructure, The candle-type microstructure according to an embodiment of the present invention may contain about 60% of the drug in the head in an amount greater than that of the conventional microstructure. In this case, the ratio of the drug that the candle-type microstructure may contain may vary depending on the shape of the head portion and the neck portion. The candle-type microstructure of the present invention may have a volume of 60 to 90% of the total volume in the height range of the upper 60% in the height direction, but is not limited thereto.

The candle-type microstructure 10 according to an embodiment of the present invention is formed such that the head portion 40 of the microstructure has a wider cross section than the neck portion 30 of the microstructure 10, and has a shape close to a spherical or elliptical shape. Consisting, it is possible to store a large amount of drugs in the interior (A), and the neck part 30 is cut in the transverse direction while the head part 40 is completely inserted into the skin, so that the head part 40 is positioned inside the skin. It has the advantage of injecting a large amount of drugs into the skin.

In addition, in the case of the triangular microstructure 100 of the prior art, the microstructure including the substrate must be in contact with the skin for a long time before the drug penetrates the skin while the drug is located inside the microstructure (B). However, in the candle-type microstructure 10 according to an embodiment of the present invention, the neck portion 30 can be quickly cut while the head portion is inserted into the skin to position the head portion 40 inside the skin. , In order to insert the head part 40 into the skin, it is possible to shorten the time for the substrate to contact the skin.

Figure 10 (a) and (b) is a case in which the candle-type microstructure according to an embodiment of the present invention is inserted into the skin (a) and when the conventional microstructure is inserted into the skin (b) it is easy to remove the skin. It is a drawing shown to explain one degree. 11 is a photograph experimentally showing (a) and (b) of FIG. 10, when a candle-type microstructure according to an embodiment of the present invention is inserted into the skin and when a conventional microstructure is inserted into the skin This is a photograph that experimentally shows the degree of easy departure.

Referring to Figures 10 (a) and (b) and Figure 11 (a) and (b), the candle-type microstructure 10 according to an embodiment of the present invention has a portion having the widest cross-section of the head When inserted into the skin, the candle-type microstructure does not easily come off the skin. That is, as can be seen in (a) and (b) of Figs. 10 and (a) and (b) of Fig. 11, the candle-type microstructure 10 does not fall out of the skin and Raise and support. This is because after the head of the candle-type microstructure 10 is inserted into the skin, the head may be fixed inside the skin due to the elasticity of the skin.

In an embodiment of the present invention, the head portion of the microstructure 10 inserted into the skin is fixed inside the skin, and as compared to the cross section of the neck portion, the widest cross section of the head portion is formed so that it is difficult to be removed from the skin. That is, as the head portion is larger and wider, the amount of force for removing the head portion from the inside of the skin increases. Compared to this, the conventional microstructure 100 in a triangular shape has a wider cross section toward the substrate in a state in which the tip of the microstructure is inserted inside the skin, so that the microstructure can be easily removed or separated from the skin even by a small force. have.

Therefore, the conventional triangular microstructure 100 has the inconvenience of maintaining a state in which the substrate supporting the microstructure is kept in contact with the skin in order to inject the drug located at the end side of the microstructure into the skin. there was.

In comparison, in the candle-type microstructure 10 according to an embodiment of the present invention, since the head portion is not easily removed from the skin while the head portion is inserted into the skin, the neck portion is broken in the transverse direction while the head portion is inserted into the skin. Thus, if the head portion is kept inserted into the skin, since the drug inside the head portion can penetrate into the skin, it has the advantage of being able to simply administer the microstructured drug into the skin.

FIG. 12 is a diagram illustrating a resistance force according to a displacement applied when a force is applied when each of the microstructures collapses when a force is applied from the end of the candle-type microstructure (a) and the conventional microstructure (b) according to an embodiment of the present invention. This is a graph comparing the size change.

Referring to FIG. 12, a displacement and rigid member in which the rigid member is moved while the needle is collapsed by the steel bar by moving the rigid member from the upper side of the microstructure while the microstructure is erected upright. The magnitude of the repulsive force applied to the was measured. According to the experimental results according to such an experiment, in the conventional microstructure (b), the repulsive force gradually increases as the displacement increases, and then 1 at a specific force (first force: 0.4N) at a specific position (first position: 0.2mm). There was an inflection point where the car collapsed, the magnitude of the repulsive force decreased slightly at the inflection point, and then the repulsive force increased rapidly according to the displacement.

In comparison, the microstructure (a) according to an embodiment of the present invention has a force smaller than the first force (0.25N) at the second position (0.14mm), which is a displacement smaller than the first position, when compared with the conventional microstructure. ), the inflection point of the first collapse occurred, and then the second collapse of the inflection point occurred at a position less than the first position. In the microstructure according to an embodiment of the present invention, after the secondary collapse, the repulsive force decreased significantly compared to that of the conventional microstructure, and the repulsive force rapidly increased after passing through the first position again. When the microstructure according to an embodiment of the present invention collapses, the repulsive force and the tendency of the force have a morphological characteristic of the candle-type microstructure, that is, the neck portion is smaller than the head portion of the microstructure, and the volume of the head portion is larger than the neck portion. Due to that.

13 is a graph showing a ratio of a microstructure according to an embodiment of the present invention and a drug contained in a conventional microstructure according to an embodiment of the present invention are administered to the skin over time.

Referring to FIG. 13, the candle-type microstructure according to an embodiment of the present invention contains a large amount of drugs in the head, so that a large amount of drugs can be injected into the skin within a short time compared to the conventional microstructure. , After a certain period of time, it can be seen that the conventional microstructure shows a drug administration rate of 90% or more compared to that of the conventional microstructure showing a drug administration rate of about 60%, so that there is an effect of more effectively administering the drug.

14 is a photograph showing a comparison of the amount of material remaining on the substrate after a predetermined period of time after the microstructure (a) according to an embodiment of the present invention and the conventional microstructure (b) are put into the skin.

As shown in FIG. 14, in the microstructure according to an embodiment of the present invention, since the neck portion and the body portion are small in volume after drug injection, there is almost no residue left on the substrate. However, the microstructure according to the prior art has a large amount of It was confirmed that the residue remained on the substrate. Accordingly, it can be seen that the microstructure according to an embodiment of the present invention has a superior effect on the drug administration rate and efficiency than the microstructure according to the prior art.

15 is a photograph for comparing a microstructure according to an embodiment of the present invention and a conventional microstructure, where (1) is a picture taken in a state in which the microstructure is formed, and (2) is 0 in a state in contact with the skin. Time, 10 minutes, and 30 minutes later are plane photographs of the state in which the drug is injected onto the skin, and (3) is a cross-sectional photograph of the drug administered inside the skin.

Referring to FIG. 15, when comparing the amount of the drug injected into the skin after a certain period of time has elapsed after the substrate provided with the microstructure is brought into contact with the skin, the microstructure according to an embodiment of the present invention is uniform and However, it can be seen that the drug is injected into the skin in a large amount clearly and evenly distributed after a predetermined period of time, but in the conventional microstructure, the state in which the drug is injected into the skin is not uniform, and the injection amount is also remarkably small. In the above experiment, the microstructure according to an embodiment of the present invention separates the patch with a predetermined force immediately after contacting the substrate, that is, the patch to which the candle-type microstructure is bonded to the skin, or after a short period of time. Although it has a convenient advantage when administering drugs using a structure, the conventional microstructure is used because the patch must be in contact with the skin until the drug contained in the microstructure is continuously injected into the skin and injection is no longer made. This has an inconvenient drawback.

In addition, in order to inject a microstructured drug into the skin, a conventional patch with microstructures has to be adhered to the skin when using by applying or attaching an adhesive material to the patch or substrate. , Pain may be felt when the patch or substrate is removed from the skin. However, in the substrate or patch having a candle-type microstructure according to an embodiment of the present invention, the substrate or patch is applied with a predetermined force after the microstructure is embedded in the skin. Since it is separated from the microstructure, it has the advantage of being easy to use because it does not have a separate adhesive material or adhesive layer.

Although an embodiment of the present invention has been described above, the spirit of the present invention is not limited to the embodiment presented in the present specification, and an average technician in the art who understands the spirit of the present invention is within the scope of the same idea. In, it will be possible to easily propose another embodiment by adding, changing, deleting, adding, or the like of components, but it will also be said to belong to the scope of the present invention.

2 substrate
4 tops
10 microstructure
20 Body
30 neck

Claims (11)

A body portion formed on the substrate and having a first cross section; The body portion includes a second cross-section smaller than the first cross-section, and includes a neck portion formed on the body portion so as to extend in a direction away from the substrate, and a third cross-section wider than the second cross-section of the neck portion, and the substrate And a head portion formed on the neck portion so as to extend in a direction away from the head portion, and the third end face of the head portion has a cross section that is wider than an end surface of the neck portion far from the substrate, and when viewed in a direction away from the substrate, the head portion It is the widest cross section among the cross-sections, and the head part is implanted into the skin while the third cross-section is inserted into the skin, and a volume of 60 to 90% of the total volume is in the range of 60% of the total height from the tip of the head part. As a method for manufacturing a candle-type microstructure comprising a continuous curved surface in a direction away from the substrate, the outer surface of the body part, the neck part, and the head part so as to have a
(a) placing the first viscous composition on a substrate;
(b) stretching the first viscous composition;
(c) placing a second viscous composition on the stretched first viscous composition; And
(d) tensioning the first viscous composition and the second viscous composition by an additional centrifugal force; including,
(b) stretching the first viscous composition may include forming a lower portion of a body, a neck, and a head on the substrate, and (b-1) placing an upper plate on the upper portion of the substrate; (b-2) applying a centrifugal force to the first viscous composition to bring the first viscous material into contact with the upper plate; And (b-3) removing the upper plate,
(d) tensioning the second viscous composition comprises forming the extension length of the candle-type microstructure including the first viscous composition and the second viscous composition longer than the previous step, and sharply extending the end of the head portion Method of manufacturing a candle-type microstructure to be made. The method of claim 1,
Positioning the second viscous composition on the stretched first viscous composition comprises applying or dropping the second viscous composition on the first viscous composition. (a) placing a first viscous composition on a substrate;
(b) molding the first viscous composition;
(c) placing a second viscous composition on the molded first viscous composition; And
(d) tensioning the first viscous composition and the second viscous composition by a centrifugal force; including,
(b) forming the first viscous composition includes forming a lower portion of a body portion, a neck portion, and a head portion on the substrate, and (b-1) placing an upper plate on the upper portion of the substrate; (b-2) contacting the first viscous material with the upper plate; And (b-3) removing the upper plate,
(d) stretching the second viscous composition comprises forming the extension length of the candle-type microstructure including the first viscous composition and the second viscous composition longer than the previous step, and sharply extending the end of the head portion. Method of manufacturing a candle-type microstructure. delete delete delete delete delete delete delete delete

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