WO2010140760A2 - Flexible microneedle patch system and method for manufacturing the same - Google Patents

Flexible microneedle patch system and method for manufacturing the same Download PDF

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Publication number
WO2010140760A2
WO2010140760A2 PCT/KR2010/001862 KR2010001862W WO2010140760A2 WO 2010140760 A2 WO2010140760 A2 WO 2010140760A2 KR 2010001862 W KR2010001862 W KR 2010001862W WO 2010140760 A2 WO2010140760 A2 WO 2010140760A2
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WO
WIPO (PCT)
Prior art keywords
microneedle
flexible substrate
photocurable resin
patch system
support film
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PCT/KR2010/001862
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French (fr)
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WO2010140760A3 (en
Inventor
Seung Seob Lee
Boo Joon Sul
Man Hee Han
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Miti Systems Inc.
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Publication date
Application filed by Miti Systems Inc. filed Critical Miti Systems Inc.
Publication of WO2010140760A2 publication Critical patent/WO2010140760A2/en
Publication of WO2010140760A3 publication Critical patent/WO2010140760A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/162—Needle sets, i.e. connections by puncture between reservoir and tube ; Connections between reservoir and tube
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023—Drug applicators using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053—Methods for producing microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0061—Methods for using microneedles

Definitions

  • the present invention relates to a flexible microneedle patch system and method for manufacturing the same, and more particularly to an improved flexible microneedle patch system which imparts flexibility so that it can be easily applied to even a face surface with a large curvature, and a method for manufacturing the same.
  • a method of delivering a drug into the body includes orally administering a drug or percutaneously administering a drug to allow the drug to be absorbed into the skin, injecting a drug into the human body through a syringe, and the like.
  • the method of orally administering a drug i.e., the oral administration method may cause adverse effects on central nervous system such as headache, dizziness, nervousness, etc., and adverse effects on gastrointestinal system such as emesis, dyspepsia, diarrhea, peptic ulcer, gastrointestinal hemorrhage, perforation etc., it is limited to only a short-term therapy.
  • transdermal administration method is one which generally applies a drug in the form of liquid formulation, cream formulation, gel formulation, etc., on the skin or simply attaches a patch (i.e., mask pack, etc.) containing a drug to the skin.
  • a transdermal administration method has a merit in that a user easily utilizes it irrespective of time and place, but still has a disadvantage a shortcoming in that since the stratum corneum which is an outermost layer of the epidermis of the skin and is 10-60 ⁇ m in depth inhibits the outflow of internal body substances and the penetration of external substances into the human body, transdermal absorption of active ingredients is extremely low.
  • the method of injecting a drug into the human body through a syringe has an advantage in that since a syringe needle is inserted into the skin to directly inject the drug into the body, active ingredients can be effectively delivered into the texture of the skin.
  • a syringe needle is inserted into the skin to directly inject the drug into the body, active ingredients can be effectively delivered into the texture of the skin.
  • such a intracutaneous injection method entails a shortcoming in that the syringe needle stimulates a plurality of pain spots widely distributed in the skin, which gives a considerable pain to a subject in use.
  • this method encounters a disadvantage in that since it is mainly used in a hospital or a professional skin care agency, it cannot be readily utilized in general homes.
  • the method involves a drawback in that since the drug is concentratedly injected only around the skin texture into which the syringe needle is inserted, the method is difficult to apply in the case where the supply of a drug to a wide area of the skin is required.
  • microneedle In order to address and solve the above problem, a microneedle has been developed which has a diameter of several tens to several hundreds of micrometers ( ⁇ m) and a length of a few hundreds to a few thousands of micrometers ( ⁇ m). Since this microneedle is relatively small in diameter and length as compared to the conventional needles, the number of pain spots stimulated is reduced, thereby resulting in significant alleviation of a pain given to the subject and making its use in general homes convenient.
  • the microneedle is used in the form of a microneedle array in which a plurality of microneedles is arranged in rows and columns.
  • microneedle has an advantage in that the drug can be supplied to even a wider area of the skin unlike the drug injection using the syringe due to the morphological characteristics of the microneedle array.
  • a research on the microneedle array particularly a research is actively in progress on a microneedle patch system in which a microneedle array and a patch attachable to the skin are combined with each other.
  • U.S. Patent No. 6,451,240 discloses a method of manufacturing a microneedle array in which a heated plastic resin is provided into a temperature-controlled microneedle mold
  • U.S. Patent Application Publication No. 2007/0191761 discloses a method of manufacturing a microneedle array through a injection molding process using a negative mold insert
  • Korean Patent No. 846,195 discloses a patch having micro-projections whose mass-production is facilitated due to a short process and a manufacturing method thereof.
  • the microneedle array and a substrate are formed integrally with each other or the microneedle array is made very thick. Since it is required that the microneedles of the microneedle array should penetrate through the stratum corneum which is an outermost layer of the epidermis of the skin and is 10-60 ⁇ m in depth, it must be fabricated by using a high-strength polymer.
  • the substrate and the microneedle array are formed integrally with each other as in the above-mentioned methods, flexibility is not imparted to the substrate. As a result, the microneedle array is applied to only a skin region without any curvature or a gentle curvature, but is difficult to apply to a skin region having a large curvature.
  • the present invention has been made in order to solve the above-described problems occurring in the prior art, and it is an object of the present invention to provide a microneedle patch system which imparts flexibility so that it can be closely adhered to even a face surface with a large curvature.
  • Another object of the present invention is to provide a method for manufacturing such a flexible microneedle patch system.
  • Yet another object of the present invention is to provide a drug delivery system adopting such a flexible microneedle patch system.
  • the present invention provides a microneedle patch system (10), including: (a) a plurality of microneedle array (11) each including a plurality of microneedles arranged therein, each microneedle being made of a photocurable resin material; (b) a flexible substrate (12) having one surface on which the microneedle array (11) is fixedly formed; and (c) a rigid support film (13) separably formed on the other surface of the flexible substrate (12) formed with the microneedle array (11).
  • each of the microneedles preferably includes a microneedle support (11a) having an extended surface bonded to the flexible substrate.
  • the flexible substrate preferably has a modulus of elasticity ranging from 1 KPa to 1 GPa, and a thickness ranging from 0.01 mm to 0.2 mm.
  • the material of the flexible substrate is preferably one any one selected from the group consisting of polyurethane, low-density polyethylene (LDPE) and high-density polyethylene (HDPE), or a mixture of at least two thereof.
  • the support film preferably has a modulus of elasticity ranging from 1 GPa to 10 GPa, and a thickness ranging from 0.05 mm to 0.5 mm.
  • the material of the support film is preferably any one selected from the group consisting of polyethylene terephtalate (PET) and polycarbonate (PC), and a mixture thereof.
  • the surface of the plurality of microneedle arrays (11) or the flexible substrate may be coated with metal, ceramic, skin-compatible polymer or the like.
  • the present invention provides a method for manufacturing a microneedle patch system (10), including the steps of: (A) applying a photocurable resin on a mold for microneedle arrays (11), and then removing air bubbles contained in the photocurable resin; (B) sequentially seating a flexible substrate and a support film (13) on the photocurable resin applied on the mold, or seating a flexible substrate and a support film (13), which have been previously laminated together, on the photocurable resin applied on the mold; (C) irradiating ultraviolet (UV) rays onto the top surface of the support film (13) to cure the photocurable resin while pressing the top surface of the support film (13), thus forming a molded product; and (D) removing the molded product from the mold.
  • A applying a photocurable resin on a mold for microneedle arrays (11), and then removing air bubbles contained in the photocurable resin
  • B sequentially seating a flexible substrate and a support film (13) on the photocurable resin applied on
  • the method for manufacturing a microneedle patch system further includes, between step (A) and (B) or step (B) and (C), a step of removing residual photocurable resin from the mold.
  • At least one of the flexible substrate and the support film is preferably made of a material having an ultraviolet (UV) ray-transmitting property.
  • UV ultraviolet
  • a secondary curing step may be further performed so as to increase the strength of the microneedles.
  • the present invention provides a drug delivery system (20) including: (a) a microneedle patch system (10) according to Claim 1 or 2; (b) an in vivo delivery substance (22) applied on a substrate surface on which a plurality of microneedle arrays (11) of the microneedle patch system are formed; and (c) a protective film (21) for preventing separation of the in vivo delivery substance (22) and damage of a plurality of microneedles constituting of each of the microneedle arrays.
  • microneedle patch system 10 which imparts flexibility so that it can be closely adhered to even a face surface with a large curvature.
  • the microneedle patch system 10 includes a support film 13 so that a flexible microneedle patch system can be prevented from being deformed or damaged in the course of manufacturing or handling the microneedle patch system 10.
  • a drug delivery system 20 adopting a flexible microneedle patch system 10 is provided so that transdermal drug delivery is further facilitated.
  • FIG. 1 shows an example of a microneedle patch system including microneedle arrays and a flexible substrate.
  • FIG. 2 shows an example of a microneedle patch system according to the present invention.
  • FIG. 3 shows an example of a microneedle patch system including a microneedle support according to the present invention.
  • FIG. 4 shows a manufacturing process of a microneedle patch system according to the present invention.
  • FIG. 5 shows a use process of a drug delivery system according to the present invention.
  • FIG. 2 shows an example of a flexible microneedle patch system according to the present invention which includes a microneedle array 11 having a plurality of microneedles arranged therein, a flexible substrate 12 having one surface on which the microneedle array 11 is fixedly formed, and a rigid support film 13 separably formed on the other surface of the flexible substrate 12 formed with the microneedle array 11.
  • a conventional patch system formed with the microneedle array is problematic in that since the microneedle array and the substrate are formed integrally with each other or the microneedle array is made very thick, the substrate cannot be bent along the curved surface of the skin.
  • the microneedle patch system according to the present invention has merits in that since the microneedle array is formed separately from the substrate as well as is made very thin, the substrate can be bent along the curved surface of the skin.
  • each microneedle preferably has a length of more than 50 ⁇ m so that micro-holes are formed in the stratum corneum of the skin to allow an in vivo delivery substance 22 (i.e., a substance to be delivered into the human body) to be penetrated into the stratum corneum.
  • an in vivo delivery substance 22 i.e., a substance to be delivered into the human body
  • the microneedle array 11 is made of a photocurable resin material.
  • the photocurable resin uses a mixture of 3,4-epoxy cyclohexyl methyl-3,4 epoxy cyclohexene carboxylate and 1 mol% of triarylsulfonium salt, but is not limited thereto. It is of course natural that a typical photocurable resin can be used. Also, the photocurable resin may contain a variety of additives for enhancement of curing speed and adjustment of viscosity
  • the microneedle patch system 10 is preferably constructed such that each of the microneedles further includes a microneedle support (11a) having an extended surface bonded to the flexible substrate as shown in FIG. 3.
  • the microneedle support 11a allows the bonding area between the microneedle and the flexible substrate 12 to be increased so that the microneedle is more rigidly fixed to the flexible substrate 12, thereby preventing separation between the microneedle array and the substrate which may occur during the use of the microneedle patch system 10.
  • the microneedle support 11a may be constructed independently from adjoining microneedle supports 11a as shown in FIG. 3(A), and may be preferably constructed such that more than two adjoining microneedle supports are connected so as to further improve the adhesion between the microneedle support 11a and the flexible substrate 12 as shown in FIG. 3(B).
  • the microneedle support 11a preferably has a thickness ranging from 0.01 mm to 0.05 mm. In this case, if too many microneedles are connected by the microneedle support 11a having the above thickness range, flexibility of the microneedle patch system is deteriorated. Thus, if the thickness of the microneedle support 11a is set to between 0.01 mm to 0.05 mm, the number of the microneedles is preferably set to less than 20% of the entire microneedle.
  • the microneedles of the microneedle array may be all connected by means of the microneedle support 11a.
  • the microneedle support 11a preferably has a thickness of less than 0.01 mm. If the thickness of the microneedle support is larger than 0.01 mm, the thickness of the entire microneedle array is increased. As a result, the entire microneedle array is not bent flexibly. Since the term thickness refers to the degree in which a target material is thick, the thickness must be larger than 0. Thus, in the present invention, the lower limit of the thickness of the microneedle substrate has no meaning.
  • the flexible substrate 12 having one surface on which the microneedle array 11 is fixedly formed has a modulus of elasticity ranging from 1 KPa to 1 GPa, and a thickness ranging from 0.01 mm to 0.2 mm so that it can be attached to even a face surface with a large curvature. If the modulus of elasticity of the flexible substrate 12 is more than 1 GPa, the flexible substrate 12 is too stiff and thus it is difficult to closely adhere the flexible substrate 12 along the curved surface of a face. On the contrary, if the modulus of elasticity of the flexible substrate 12 is less than 1 KPa, the microneedle sheet is too easily folded, making it difficult to handle.
  • a phenomenon may occur in which the flexible substrate stretches in a step of removing a molded product from the mold during the manufacturing process.
  • the thickness of the flexible substrate 12 is larger than 0.2 mm, the flexible substrate 12 is too stiff and thus it is difficult to closely adhere the flexible substrate 12 along the curved surface of a face.
  • the thickness of the flexible substrate 12 is smaller than 0.01 mm, the flexible substrate 12 is too thin and thus is apt to be torn. Consequently, the manufacture and handling of the microneedle patch system may not be facilitated.
  • the material of the flexible substrate 12 preferably has a ultraviolet (UV) rays-transmitting property so that ultraviolet (UV) rays can be transferred to a photocurable resin of which the microneedle array 11 is made so as to promote the curing of the photocurable resin during the process of manufacturing the microneedle patch system 10 which will be described later.
  • UV ultraviolet
  • the material of the flexible substrate 12 uses polyurethane, but may be properly selected from the group consisting of low-density polyethylene (LDPE), high-density polyethylene (HDPE), and a mixture thereof by those skilled in the art.
  • FIG. 1 shows an example of a microneedle patch system 10 including microneedle arrays 11 and a flexible substrate 12. If the microneedle patch system 10 includes only the flexible substrate 12 and the microneedle array 11 as constituent elements, the flexible substrate 12 is easily bent or folded so that a manufacturer of the microneedle patch system 10 including the flexible substrate 12 or a user of a drug delivery system 20 employing the microneedle patch system 10 must pay considerable attention to the handling of the system.
  • a support film 13 made of a material which is relatively rigid as compared to that of the flexible substrate 12 is formed on the other surface of the flexible substrate 12 formed with the microneedle array 11 so that the flexible substrate 12 can be effectively prevented from bent or folded in the course of manufacturing and using the microneedle patch system 10.
  • the support film 13 preferably has a modulus of elasticity ranging from 1 GPa to 10 GPa, and a thickness ranging from 0.05 mm to 0.5 mm. If the modulus of elasticity and the thickness of the flexible substrate 12 is less than 1 GPa and 0.05 mm, respectively, a function of preventing the flexible substrate 12 from being bent or folded can be deteriorated.
  • the material of the support film 13 preferably has a ultraviolet (UV) rays-transmitting property so that ultraviolet (UV) rays can be transferred to a photocurable resin of which the microneedle array 11 is made so as to promote the curing of the photocurable resin during the process of manufacturing the microneedle patch system 10 which will be described later similarly to the case of the flexible substrate 12.
  • UV ultraviolet
  • the material of the support film 13 uses polyethylene terephtalate (PET), but may be properly selected from the group consisting of polycarbonate (PC), polymethylmethalcrylate (PMMA), polypropylene (PP), polyimide, etc., by those skilled in the art.
  • the support film 13 is preferably constructed separately from the flexible substrate 12 so as to removed from the flexible substrate 12 so that when a drug delivery system 20 which will be described alter is attached to the skin, the flexible substrate 12 of the drug delivery system 20 can be closely adhered completely along the curved surface of the skin.
  • the microneedle patch system 10 is preferably coated with a metal material such as gold, a ceramic material such as titanium dioxide (TiO 2 ), titanium nitride (TiN) or the like, a hydrophilic polymer material such as ethylene-vinyl alcohol (EVOH), a skin-compatible polymer material such as parylene or polyurethane, or the like to improve the compatibility between the microneedle and the skin and achieve a uniform application of a drug to be delivered into the body.
  • a metal material such as gold
  • a ceramic material such as titanium dioxide (TiO 2 ), titanium nitride (TiN) or the like
  • a hydrophilic polymer material such as ethylene-vinyl alcohol (EVOH)
  • EVOH ethylene-vinyl alcohol
  • parylene or polyurethane a skin-compatible polymer material
  • the microneedle patch system is manufactured by a method for manufacturing the microneedle patch system.
  • the method includes: (A) applying a photocurable resin on a mold for microneedle arrays 11, and then removing air bubbles contained in the photocurable resin; (B) sequentially seating a flexible substrate 12 and a support film 13 on the photocurable resin applied on the mold, or seating a flexible substrate 12 and a support film 13, which have been previously laminated together, on the photocurable resin applied on the mold; (C) irradiating ultraviolet (UV) rays onto the top surface of the support film (13) to cure the photocurable resin while pressing the top surface of the support film (13), thus forming a molded product; and (D) removing the molded product from the mold.
  • UV ultraviolet
  • FIG. 4 shows a manufacturing process of a microneedle patch system according to the present invention.
  • a hot embossing process is a molding technique which presses a polymeric material heated to a temperature more than a glass transition temperature using a molding device having micropatterns imprinted thereon to form a micro-pattern of a mold.
  • Such a hot embossing process has an advantage in that a number of micropatterns or microstructures can be formed by performing a press process one time.
  • the manufacturing method of the microneedle patch system 10 employs a UV embossing process.
  • microneedle patch system 10 The manufacturing method of the microneedle patch system 10 according to the present invention will be described in detail hereinafter.
  • the mold is formed such that the shape of the microneedle is carved in intaglio. Since the mold can be manufactured by a known technique, a separate description thereof will be omitted.
  • the mold is preferably made of a material which can transmit UV rays to allow the UV rays to reach the photocurable resin in a step of curing the photocurable resin.
  • a photocurable resin is applied on a mold for microneedle arrays 11, and then air bubbles contained in the photocurable resin is removed.
  • the photocurable resin is applied on the mold by using a photocurable resin dispenser, but the photocurable resin application method may be selected properly according to the convenience of those skilled in the art.
  • the mold applied with the photocurable resin is placed in a vacuum chamber, and then air bubbles, i.e., air entrained in the resin is removed using a vacuum pump P.
  • a residual photocurable resin remained on the surface of the mold is removed.
  • all the photocurable resins on the surface of the mold except a negative mold having the shape of the microneedle are removed.
  • the photocurable resin remained on the surface of the mold is removed so that is has a thickness of less than 0.01mm.
  • a doctor blade method, a press roller or the like may be selected by those skilled in the art.
  • the step of removing the residual photocurable resin may be performed after first seating the flexible substrate 12 and the support film 13 on the photocurable resin applied on the mold according to the convenience of those skilled in the art.
  • the doctor blade method is one in which the residual photocurable resin is scratched.
  • the step of removing the residual photocurable resin is performed before seating the flexible substrate 12 and the support film 13 on the photocurable resin, a resin removing effect is excellent, but the step of removing the residual photocurable resin may be performed after seating the flexible substrate 12 and the support film 13.
  • the press roller seats the flexible substrate 12 and the support film 13 in such a fashion as to squeeze the residual photocurable resin and then the step of removing the residual photocurable resin is performed, a resin removing effect is excellent, but the step of removing the residual photocurable resin may be performed before seating the flexible substrate 12 and the support film 13.
  • the respective microneedles are connected together or the microneedle array itself becomes thick, thereby degrading flexibility of the entire microneedle patch system 10.
  • the polymer as the material of the flexible substrate 12 and the support film 13 is seated on the photocurable resin applied on the mold.
  • a laminated film is used in which the polymer films as the material of the flexible substrate 12 and the support film 13 have been previously laminated.
  • the laminated film may be used in the form of a predetermined size, i.e., in the form cut into a size similar to that of the mold, but is preferably used in the form of a roll for the purpose of a continuous process so that the laminated film is seated on the photocurable resin and then cut to a given size.
  • UV rays are irradiated onto the top surface of the support film 13 to cure the photocurable resin.
  • a phenomenon occurs in which the polymeric film is released from the photocurable resin.
  • the UV curing process is preferably performed under the pressing conditions in which a pressure ranges from 10 KPa to 1,000 KPa of in order to improve the adhesion between the photocurable resin and the polymeric film. If the pressure is less than 10 KPa, the adhesion between the photocurable resin and the polymeric film is decreased.
  • UV rays were irradiated onto the top surface of the support film 13 for 300 seconds using a 15 mW mercury lamp as a UV lamp, but the UV irradiation conditions are not limited thereto and may be of course changed by those skilled in the art depending to the kinds of the photocurable resin.
  • the UV rays should be transferred to the photocurable resin through the mold and the polymeric film (i.e., the flexible substrate 12 and the support film 13), at least on of the mold and the polymeric film is preferably made of a material which transmits the UV rays.
  • a molded product i.e., a microneedle patch system 10 is removed from the mold. Thereafter, a secondary curing step may be further performed so as to increase the strength of the microneedles.
  • the drug delivery system 20 includes the above-mentioned microneedle patch system 10, an in vivo delivery substance 22 applied on the surface of a flexible substrate 12 on which a plurality of microneedle arrays 11 of the microneedle patch system are formed, and a protective film (21) for preventing separation of the in vivo delivery substance (22) and damage of the distal ends of microneedles.
  • a hormone formulation, a vitamin formulation or the like may be properly selected as the in vivo delivery substance 22 depending on the use purpose.
  • the in vivo delivery substance 22 contains an adhesive component for easy attachment to the skin. Since the adhesive component can be properly selected by those skilled in the art using a known technique, a separate description thereof will be omitted in the present invention.
  • the protective film 21 is preferably made of a soft material such as rubber or sponge. If the protective film 21 is made of a material which is hard and stiff, a problem may occur in which the distal end of the microneedle becomes rather blunt or is broken by hardness or stiffness of the protective film 21.
  • FIG. 5 shows the case where after the drug delivery system 20 is attached to the skin and then the support film 13 is removed from the drug delivery system 20. In this case, the support film 13 may be removed from the drug delivery system 20 immediately before attaching the drug delivery system 20 to the skin.

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Abstract

The present invention relates to a flexible microneedle patch system and method for manufacturing the same. The microneedle patch system includes: a microneedle array (11) each including a plurality of microneedles arranged therein, each microneedle being made of a photocurable resin material; a flexible substrate (12) having one surface on which the microneedle array (11) is fixedly formed; and a rigid support film (13) separably formed on the other surface of the flexible substrate (12) formed with the microneedle array (11). Also, a method for manufacturing a microneedle patch system (10), including the steps of: (A) applying a photocurable resin on a mold for microneedle arrays (11), and then removing air bubbles contained in the photocurable resin; (B) sequentially seating a flexible substrate and a support film (13) on the photocurable resin applied on the mold, or seating a flexible substrate and a support film (13), which have been previously laminated together, on the photocurable resin applied on the mold; (C) irradiating ultraviolet (UV) rays onto the top surface of the support film (13) to cure the photocurable resin while pressing the top surface of the support film (13), thus forming a molded product; and (D) removing the molded product from the mold.

Description

FLEXIBLE MICRONEEDLE PATCH SYSTEM AND METHOD FOR MANUFACTURING THE SAME
The present invention relates to a flexible microneedle patch system and method for manufacturing the same, and more particularly to an improved flexible microneedle patch system which imparts flexibility so that it can be easily applied to even a face surface with a large curvature, and a method for manufacturing the same.
In general, a method of delivering a drug into the body includes orally administering a drug or percutaneously administering a drug to allow the drug to be absorbed into the skin, injecting a drug into the human body through a syringe, and the like.
Among these methods, since the method of orally administering a drug, i.e., the oral administration method may cause adverse effects on central nervous system such as headache, dizziness, nervousness, etc., and adverse effects on gastrointestinal system such as emesis, dyspepsia, diarrhea, peptic ulcer, gastrointestinal hemorrhage, perforation etc., it is limited to only a short-term therapy.
The method of percutaneously administering a drug, i.e., transdermal administration method is one which generally applies a drug in the form of liquid formulation, cream formulation, gel formulation, etc., on the skin or simply attaches a patch (i.e., mask pack, etc.) containing a drug to the skin. Such a transdermal administration method has a merit in that a user easily utilizes it irrespective of time and place, but still has a disadvantage a shortcoming in that since the stratum corneum which is an outermost layer of the epidermis of the skin and is 10-60 ㎛ in depth inhibits the outflow of internal body substances and the penetration of external substances into the human body, transdermal absorption of active ingredients is extremely low.
The method of injecting a drug into the human body through a syringe has an advantage in that since a syringe needle is inserted into the skin to directly inject the drug into the body, active ingredients can be effectively delivered into the texture of the skin. However, such a intracutaneous injection method entails a shortcoming in that the syringe needle stimulates a plurality of pain spots widely distributed in the skin, which gives a considerable pain to a subject in use. Also, this method encounters a disadvantage in that since it is mainly used in a hospital or a professional skin care agency, it cannot be readily utilized in general homes. In addition, the method involves a drawback in that since the drug is concentratedly injected only around the skin texture into which the syringe needle is inserted, the method is difficult to apply in the case where the supply of a drug to a wide area of the skin is required.
In order to address and solve the above problem, a microneedle has been developed which has a diameter of several tens to several hundreds of micrometers (㎛) and a length of a few hundreds to a few thousands of micrometers (㎛). Since this microneedle is relatively small in diameter and length as compared to the conventional needles, the number of pain spots stimulated is reduced, thereby resulting in significant alleviation of a pain given to the subject and making its use in general homes convenient. The microneedle is used in the form of a microneedle array in which a plurality of microneedles is arranged in rows and columns. Such a microneedle has an advantage in that the drug can be supplied to even a wider area of the skin unlike the drug injection using the syringe due to the morphological characteristics of the microneedle array. Thus, a research on the microneedle array, particularly a research is actively in progress on a microneedle patch system in which a microneedle array and a patch attachable to the skin are combined with each other.
In order to solve such an inconvenience, U.S. Patent No. 6,451,240 discloses a method of manufacturing a microneedle array in which a heated plastic resin is provided into a temperature-controlled microneedle mold, and U.S. Patent Application Publication No. 2007/0191761 discloses a method of manufacturing a microneedle array through a injection molding process using a negative mold insert, and Korean Patent No. 846,195 discloses a patch having micro-projections whose mass-production is facilitated due to a short process and a manufacturing method thereof.
However, according to the above conventional methods, the microneedle array and a substrate are formed integrally with each other or the microneedle array is made very thick. Since it is required that the microneedles of the microneedle array should penetrate through the stratum corneum which is an outermost layer of the epidermis of the skin and is 10-60 ㎛ in depth, it must be fabricated by using a high-strength polymer. However, if the substrate and the microneedle array are formed integrally with each other as in the above-mentioned methods, flexibility is not imparted to the substrate. As a result, the microneedle array is applied to only a skin region without any curvature or a gentle curvature, but is difficult to apply to a skin region having a large curvature.
The present invention has been made in order to solve the above-described problems occurring in the prior art, and it is an object of the present invention to provide a microneedle patch system which imparts flexibility so that it can be closely adhered to even a face surface with a large curvature.
Another object of the present invention is to provide a method for manufacturing such a flexible microneedle patch system.
Yet another object of the present invention is to provide a drug delivery system adopting such a flexible microneedle patch system.
(A) Microneedle patch system
To achieve the above objects, in one aspect, the present invention provides a microneedle patch system (10), including: (a) a plurality of microneedle array (11) each including a plurality of microneedles arranged therein, each microneedle being made of a photocurable resin material; (b) a flexible substrate (12) having one surface on which the microneedle array (11) is fixedly formed; and (c) a rigid support film (13) separably formed on the other surface of the flexible substrate (12) formed with the microneedle array (11).
In the microneedle patch system (10), each of the microneedles preferably includes a microneedle support (11a) having an extended surface bonded to the flexible substrate.
The flexible substrate preferably has a modulus of elasticity ranging from 1 KPa to 1 GPa, and a thickness ranging from 0.01 mm to 0.2 mm. Also, the material of the flexible substrate is preferably one any one selected from the group consisting of polyurethane, low-density polyethylene (LDPE) and high-density polyethylene (HDPE), or a mixture of at least two thereof.
The support film preferably has a modulus of elasticity ranging from 1 GPa to 10 GPa, and a thickness ranging from 0.05 mm to 0.5 mm. In addition, the material of the support film is preferably any one selected from the group consisting of polyethylene terephtalate (PET) and polycarbonate (PC), and a mixture thereof.
Besides, the surface of the plurality of microneedle arrays (11) or the flexible substrate may be coated with metal, ceramic, skin-compatible polymer or the like.
(B) Manufacturing method of microneedle patch system
To achieve the above objects, in another aspect, the present invention provides a method for manufacturing a microneedle patch system (10), including the steps of: (A) applying a photocurable resin on a mold for microneedle arrays (11), and then removing air bubbles contained in the photocurable resin; (B) sequentially seating a flexible substrate and a support film (13) on the photocurable resin applied on the mold, or seating a flexible substrate and a support film (13), which have been previously laminated together, on the photocurable resin applied on the mold; (C) irradiating ultraviolet (UV) rays onto the top surface of the support film (13) to cure the photocurable resin while pressing the top surface of the support film (13), thus forming a molded product; and (D) removing the molded product from the mold.
Preferably, the method for manufacturing a microneedle patch system further includes, between step (A) and (B) or step (B) and (C), a step of removing residual photocurable resin from the mold.
At least one of the flexible substrate and the support film is preferably made of a material having an ultraviolet (UV) ray-transmitting property.
After step (D), a secondary curing step may be further performed so as to increase the strength of the microneedles.
(C) Drug delivery system
To achieve the above objects, in yet another aspect, the present invention provides a drug delivery system (20) including: (a) a microneedle patch system (10) according to Claim 1 or 2; (b) an in vivo delivery substance (22) applied on a substrate surface on which a plurality of microneedle arrays (11) of the microneedle patch system are formed; and (c) a protective film (21) for preventing separation of the in vivo delivery substance (22) and damage of a plurality of microneedles constituting of each of the microneedle arrays.
As described above, according to the present invention, it is possible to provide a microneedle patch system 10 which imparts flexibility so that it can be closely adhered to even a face surface with a large curvature.
The microneedle patch system 10 according to the present invention includes a support film 13 so that a flexible microneedle patch system can be prevented from being deformed or damaged in the course of manufacturing or handling the microneedle patch system 10.
In addition, a drug delivery system 20 adopting a flexible microneedle patch system 10 is provided so that transdermal drug delivery is further facilitated.
FIG. 1 shows an example of a microneedle patch system including microneedle arrays and a flexible substrate.
FIG. 2 shows an example of a microneedle patch system according to the present invention.
FIG. 3 shows an example of a microneedle patch system including a microneedle support according to the present invention.
FIG. 4 shows a manufacturing process of a microneedle patch system according to the present invention.
FIG. 5 shows a use process of a drug delivery system according to the present invention.
Hereinafter, the present invention will be described in detail in connection with the preferred embodiments with reference to the accompanying drawings. However, these embodiments are for illustrative purposes, and the scope of the present invention is not limited thereto. Also, it will be understood by those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit and scope of the appended claims based on the illustrative embodiments.
FIG. 2 shows an example of a flexible microneedle patch system according to the present invention which includes a microneedle array 11 having a plurality of microneedles arranged therein, a flexible substrate 12 having one surface on which the microneedle array 11 is fixedly formed, and a rigid support film 13 separably formed on the other surface of the flexible substrate 12 formed with the microneedle array 11.
A conventional patch system formed with the microneedle array is problematic in that since the microneedle array and the substrate are formed integrally with each other or the microneedle array is made very thick, the substrate cannot be bent along the curved surface of the skin. On the contrary, the microneedle patch system according to the present invention has merits in that since the microneedle array is formed separately from the substrate as well as is made very thin, the substrate can be bent along the curved surface of the skin.
Since a concrete shape of each of the microneedles constituting the microneedle array 11 can apply a known technique, it is not referred separately in the present invention. But, each microneedle preferably has a length of more than 50㎛ so that micro-holes are formed in the stratum corneum of the skin to allow an in vivo delivery substance 22 (i.e., a substance to be delivered into the human body) to be penetrated into the stratum corneum.
The microneedle array 11 is made of a photocurable resin material. In the present invention, the photocurable resin uses a mixture of 3,4-epoxy cyclohexyl methyl-3,4 epoxy cyclohexene carboxylate and 1 mol% of triarylsulfonium salt, but is not limited thereto. It is of course natural that a typical photocurable resin can be used. Also, the photocurable resin may contain a variety of additives for enhancement of curing speed and adjustment of viscosity
The microneedle patch system 10 according to the present invention is preferably constructed such that each of the microneedles further includes a microneedle support (11a) having an extended surface bonded to the flexible substrate as shown in FIG. 3. The microneedle support 11a allows the bonding area between the microneedle and the flexible substrate 12 to be increased so that the microneedle is more rigidly fixed to the flexible substrate 12, thereby preventing separation between the microneedle array and the substrate which may occur during the use of the microneedle patch system 10.
The microneedle support 11a may be constructed independently from adjoining microneedle supports 11a as shown in FIG. 3(A), and may be preferably constructed such that more than two adjoining microneedle supports are connected so as to further improve the adhesion between the microneedle support 11a and the flexible substrate 12 as shown in FIG. 3(B). The microneedle support 11a preferably has a thickness ranging from 0.01 mm to 0.05 mm. In this case, if too many microneedles are connected by the microneedle support 11a having the above thickness range, flexibility of the microneedle patch system is deteriorated. Thus, if the thickness of the microneedle support 11a is set to between 0.01 mm to 0.05 mm, the number of the microneedles is preferably set to less than 20% of the entire microneedle.
In order to maximize the adhesion between the microneedle array 11 and the flexible substrate 12, the microneedles of the microneedle array may be all connected by means of the microneedle support 11a. In this case, the microneedle support 11a preferably has a thickness of less than 0.01 mm. If the thickness of the microneedle support is larger than 0.01 mm, the thickness of the entire microneedle array is increased. As a result, the entire microneedle array is not bent flexibly. Since the term thickness refers to the degree in which a target material is thick, the thickness must be larger than 0. Thus, in the present invention, the lower limit of the thickness of the microneedle substrate has no meaning.
Preferably, the flexible substrate 12 having one surface on which the microneedle array 11 is fixedly formed has a modulus of elasticity ranging from 1 KPa to 1 GPa, and a thickness ranging from 0.01 mm to 0.2 mm so that it can be attached to even a face surface with a large curvature. If the modulus of elasticity of the flexible substrate 12 is more than 1 GPa, the flexible substrate 12 is too stiff and thus it is difficult to closely adhere the flexible substrate 12 along the curved surface of a face. On the contrary, if the modulus of elasticity of the flexible substrate 12 is less than 1 KPa, the microneedle sheet is too easily folded, making it difficult to handle. Also, a phenomenon may occur in which the flexible substrate stretches in a step of removing a molded product from the mold during the manufacturing process. Meanwhile, if the thickness of the flexible substrate 12 is larger than 0.2 mm, the flexible substrate 12 is too stiff and thus it is difficult to closely adhere the flexible substrate 12 along the curved surface of a face. On the contrary, if the thickness of the flexible substrate 12 is smaller than 0.01 mm, the flexible substrate 12 is too thin and thus is apt to be torn. Consequently, the manufacture and handling of the microneedle patch system　may not be facilitated.
The material of the flexible substrate 12 preferably has a ultraviolet (UV) rays-transmitting property so that ultraviolet (UV) rays can be transferred to a photocurable resin of which the microneedle array 11 is made so as to promote the curing of the photocurable resin during the process of manufacturing the microneedle patch system 10 which will be described later. In the present invention, it is of course natural that the material of the flexible substrate 12 uses polyurethane, but may be properly selected from the group consisting of low-density polyethylene (LDPE), high-density polyethylene (HDPE), and a mixture thereof by those skilled in the art.
FIG. 1 shows an example of a microneedle patch system 10 including microneedle arrays 11 and a flexible substrate 12. If the microneedle patch system 10 includes only the flexible substrate 12 and the microneedle array 11 as constituent elements, the flexible substrate 12 is easily bent or folded so that a manufacturer of the microneedle patch system 10 including the flexible substrate 12 or a user of a drug delivery system 20 employing the microneedle patch system 10 must pay considerable attention to the handling of the system.
To this end, the microneedle patch system 10 as shown in FIGs. 2 and 3, a support film 13 made of a material which is relatively rigid as compared to that of the flexible substrate 12 is formed on the other surface of the flexible substrate 12 formed with the microneedle array 11 so that the flexible substrate 12 can be effectively prevented from bent or folded in the course of manufacturing and using the microneedle patch system 10. The support film 13 preferably has a modulus of elasticity ranging from 1 GPa to 10 GPa, and a thickness ranging from 0.05 mm to 0.5 mm. If the modulus of elasticity and the thickness of the flexible substrate 12 is less than 1 GPa and 0.05 mm, respectively, a function of preventing the flexible substrate 12 from being bent or folded can be deteriorated.
The material of the support film 13 preferably has a ultraviolet (UV) rays-transmitting property so that ultraviolet (UV) rays can be transferred to a photocurable resin of which the microneedle array 11 is made so as to promote the curing of the photocurable resin during the process of manufacturing the microneedle patch system 10 which will be described later similarly to the case of the flexible substrate 12. In the present invention, it is of course natural that the material of the support film 13 uses polyethylene terephtalate (PET), but may be properly selected from the group consisting of polycarbonate (PC), polymethylmethalcrylate (PMMA), polypropylene (PP), polyimide, etc., by those skilled in the art.
The support film 13 is preferably constructed separately from the flexible substrate 12 so as to removed from the flexible substrate 12 so that when a drug delivery system 20 which will be described alter is attached to the skin, the flexible substrate 12 of the drug delivery system 20 can be closely adhered completely along the curved surface of the skin.
The microneedle patch system 10 according to the present invention is preferably coated with a metal material such as gold, a ceramic material such as titanium dioxide (TiO2), titanium nitride (TiN) or the like, a hydrophilic polymer material such as ethylene-vinyl alcohol (EVOH), a skin-compatible polymer material such as parylene or polyurethane, or the like to improve the compatibility between the microneedle and the skin and achieve a uniform application of a drug to be delivered into the body. In this case, it is of course natural that the coated material is not harmful to the human body.
The microneedle patch system is manufactured by a method for manufacturing the microneedle patch system. The method includes: (A) applying a photocurable resin on a mold for microneedle arrays 11, and then removing air bubbles contained in the photocurable resin; (B) sequentially seating a flexible substrate 12 and a support film 13 on the photocurable resin applied on the mold, or seating a flexible substrate 12 and a support film 13, which have been previously laminated together, on the photocurable resin applied on the mold; (C) irradiating ultraviolet (UV) rays onto the top surface of the support film (13) to cure the photocurable resin while pressing the top surface of the support film (13), thus forming a molded product; and (D) removing the molded product from the mold.
FIG. 4 shows a manufacturing process of a microneedle patch system according to the present invention.
Generally, a hot embossing process is a molding technique which presses a polymeric material heated to a temperature more than a glass transition temperature using a molding device having micropatterns imprinted thereon to form a micro-pattern of a mold. Such a hot embossing process has an advantage in that a number of micropatterns or microstructures can be formed by performing a press process one time.
However, in the present invention, since the materials of the microneedle array 11 and the flexible substrate 12 are different from each other, when a general hot embossing process is performed, there is caused a problem in that a polymer film as a material of the flexible substrate 12 is melt or deformed. In order to solve this problem, the manufacturing method of the microneedle patch system 10 employs a UV embossing process.
The manufacturing method of the microneedle patch system 10 according to the present invention will be described in detail hereinafter.
The mold is formed such that the shape of the microneedle is carved in intaglio. Since the mold can be manufactured by a known technique, a separate description thereof will be omitted. The mold is preferably made of a material which can transmit UV rays to allow the UV rays to reach the photocurable resin in a step of curing the photocurable resin.
First, a photocurable resin is applied on a mold for microneedle arrays 11, and then air bubbles contained in the photocurable resin is removed.
In the present invention, the photocurable resin is applied on the mold by using a photocurable resin dispenser, but the photocurable resin application method may be selected properly according to the convenience of those skilled in the art. The mold applied with the photocurable resin is placed in a vacuum chamber, and then air bubbles, i.e., air entrained in the resin is removed using a vacuum pump P.
When the removal of the air bubbles contained in the resin has been completed, a residual photocurable resin remained on the surface of the mold is removed. In this case, preferably, all the photocurable resins on the surface of the mold except a negative mold having the shape of the microneedle are removed. Alternatively, preferably, the photocurable resin remained on the surface of the mold is removed so that is has a thickness of less than 0.01mm. As a method of removing the residual photocurable resin, a doctor blade method, a press roller or the like may be selected by those skilled in the art.
The step of removing the residual photocurable resin may be performed after first seating the flexible substrate 12 and the support film 13 on the photocurable resin applied on the mold according to the convenience of those skilled in the art. For example, the doctor blade method is one in which the residual photocurable resin is scratched. When the step of removing the residual photocurable resin is performed before seating the flexible substrate 12 and the support film 13 on the photocurable resin, a resin removing effect is excellent, but the step of removing the residual photocurable resin may be performed after seating the flexible substrate 12 and the support film 13. When the press roller seats the flexible substrate 12 and the support film 13 in such a fashion as to squeeze the residual photocurable resin and then the step of removing the residual photocurable resin is performed, a resin removing effect is excellent, but the step of removing the residual photocurable resin may be performed before seating the flexible substrate 12 and the support film 13.
Unless the residual photocurable resin is removed, the respective microneedles are connected together or the microneedle array itself becomes thick, thereby degrading flexibility of the entire microneedle patch system 10.
After removing the residual photocurable resin, the polymer as the material of the flexible substrate 12 and the support film 13 is seated on the photocurable resin applied on the mold. Preferably, for the sake of convenience of work and reduction in the number of the processes, a laminated film is used in which the polymer films as the material of the flexible substrate 12 and the support film 13 have been previously laminated. The laminated film may be used in the form of a predetermined size, i.e., in the form cut into a size similar to that of the mold, but is preferably used in the form of a roll for the purpose of a continuous process so that the laminated film is seated on the photocurable resin and then cut to a given size.
Subsequently, ultraviolet (UV) rays are irradiated onto the top surface of the support film 13 to cure the photocurable resin. In this case, when a general UV curing process is performed, a phenomenon occurs in which the polymeric film is released from the photocurable resin. Thus, the UV curing process is preferably performed under the pressing conditions in which a pressure ranges from 10 KPa to 1,000 KPa of in order to improve the adhesion between the photocurable resin and the polymeric film. If the pressure is less than 10 KPa, the adhesion between the photocurable resin and the polymeric film is decreased. On the contrary, if the pressure is more than 1,000 KPa, the adhesion between the photocurable resin and the polymeric film is no longer increased, deteriorating the efficiency. In the present invention, ultraviolet (UV) rays were irradiated onto the top surface of the support film 13 for 300 seconds using a 15 mW mercury lamp as a UV lamp, but the UV irradiation conditions are not limited thereto and may be of course changed by those skilled in the art depending to the kinds of the photocurable resin.
In this case, since it is required that the UV rays should be transferred to the photocurable resin through the mold and the polymeric film (i.e., the flexible substrate 12 and the support film 13), at least on of the mold and the polymeric film is preferably made of a material which transmits the UV rays.
When the photocurable resin is cured, a molded product, i.e., a microneedle patch system 10 is removed from the mold. Thereafter, a secondary curing step may be further performed so as to increase the strength of the microneedles.
In addition, the drug delivery system 20 according to the present invention includes the above-mentioned microneedle patch system 10, an in vivo delivery substance 22 applied on the surface of a flexible substrate 12 on which a plurality of microneedle arrays 11 of the microneedle patch system are formed, and a protective film (21) for preventing separation of the in vivo delivery substance (22) and damage of the distal ends of microneedles.
A hormone formulation, a vitamin formulation or the like may be properly selected as the in vivo delivery substance 22 depending on the use purpose. Preferably, the in vivo delivery substance 22 contains an adhesive component for easy attachment to the skin. Since the adhesive component can be properly selected by those skilled in the art using a known technique, a separate description thereof will be omitted in the present invention.
The protective film 21 is preferably made of a soft material such as rubber or sponge. If the protective film 21 is made of a material which is hard and stiff, a problem may occur in which the distal end of the microneedle becomes rather blunt or is broken by hardness or stiffness of the protective film 21.
The use method of the drug delivery system 20 according to the present invention will be described in brief hereinafter with reference to FIG. 5.
After the protective film 21 is removed from the drug delivery system 20 in which the in vivo delivery substance 22 is applied on the flexible substrate 12, the drug delivery system 20 is attached to a skin region to which it will be applied. Thereafter, the support film 13 is removed from the microneedle patch system 10, and the drug delivery system 20 is closely adhered to the curved surface of the skin so that the in vivo delivery substance 22 applied on the flexible substrate 12 can be transferred to the texture of the stratum corneum of the skin through the microholes formed on the skin by the microneedles. FIG. 5 shows the case where after the drug delivery system 20 is attached to the skin and then the support film 13 is removed from the drug delivery system 20. In this case, the support film 13 may be removed from the drug delivery system 20 immediately before attaching the drug delivery system 20 to the skin.
While the present invention has been described with reference to the particular illustrative embodiments, it is not to be restricted by the embodiments but only by the appended claims. It is to be appreciated that those skilled in the art can change or modify the embodiments without departing from the scope and spirit of the present invention.

Claims (12)

  1. A microneedle patch system (10), comprising:
    (a) a plurality of microneedle array (11) each including a plurality of microneedles arranged therein, each microneedle being made of a photocurable resin material;
    (b) a flexible substrate (12) having one surface on which the microneedle array (11) is fixedly formed; and
    (c) a rigid support film (13) separably formed on the other surface of the flexible substrate (12) formed with the microneedle array (11).
  2. The microneedle patch system (10) according to Claim 1, wherein each of the microneedles includes a microneedle support (11a) having an extended surface bonded to the flexible substrate.
  3. The microneedle patch system (10) according to Claim 1 or 2, wherein the flexible substrate has a modulus of elasticity ranging from 1 KPa to 1 GPa, and a thickness ranging from 0.01 mm to 0.2 mm.
  4. The microneedle patch system (10) according to Claim 1 or 2, wherein the support film has a modulus of elasticity ranging from 1 GPa to 10 GPa, and a thickness ranging from 0.05 mm to 0.5 mm.
  5. The microneedle patch system (10) according to Claim 3, wherein the material of the flexible substrate is one any one selected from the group consisting of polyurethane, low-density polyethylene (LDPE) and high-density polyethylene (HDPE), or a mixture of at least two thereof.
  6. The microneedle patch system (10) according to Claim 4, wherein the material of the support film is any one selected from the group consisting of polyethylene terephtalate (PET) and polycarbonate (PC), and a mixture thereof.
  7. The microneedle patch system (10) according to Claim 1 or 2, wherein the surface of the plurality of microneedle arrays (11) or the flexible substrate is coated with any one of metal, ceramic and polymer.
  8. A method for manufacturing a microneedle patch system (10), comprising the steps of:
    (A) applying a photocurable resin on a mold for microneedle arrays (11), and then removing air bubbles contained in the photocurable resin;
    (B) sequentially seating a flexible substrate and a support film (13) on the photocurable resin applied on the mold, or seating a flexible substrate and a support film (13), which have been previously laminated together, on the photocurable resin applied on the mold;
    (C) irradiating ultraviolet (UV) rays onto the top surface of the support film (13) to cure the photocurable resin while pressing the top surface of the support film (13), thus forming a molded product; and
    (D) removing the molded product from the mold.
  9. The method according to claim 8, further comprising, between step (A) and (B) or step (B) and (C), a step of removing residual photocurable resin from the mold.
  10. The method according to claim 8 or 9, wherein at least one of the mold, the flexible substrate and the support film is made of a material having an ultraviolet (UV) ray-transmitting property.
  11. The method according to claim 8 or 9, wherein after step (D), a secondary curing step is further performed.
  12. A drug delivery system (20) comprising:
    (a) a microneedle patch system (10) according to Claim 1 or 2;
    (b) an in vivo delivery substance (22) applied on a substrate surface on which a plurality of microneedle arrays (11) of the microneedle patch system are formed; and
    (c) a protective film (21) for preventing separation of the in vivo delivery substance (22) and damage of a plurality of microneedles constituting of each of the microneedle arrays.
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JP2014113318A (en) * 2012-12-10 2014-06-26 Toppan Printing Co Ltd Device and method for producing needle-like structure
CN104069585A (en) * 2014-07-03 2014-10-01 游学秋 Separable microneedle system and manufacturing method thereof
CN104140075A (en) * 2014-07-15 2014-11-12 中国科学院半导体研究所 Method for manufacturing hard microneedle array on surface of flexible substrate
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