WO2017176077A1 - Microneedle using biodegradable metal - Google Patents

Microneedle using biodegradable metal Download PDF

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Publication number
WO2017176077A1
WO2017176077A1 PCT/KR2017/003792 KR2017003792W WO2017176077A1 WO 2017176077 A1 WO2017176077 A1 WO 2017176077A1 KR 2017003792 W KR2017003792 W KR 2017003792W WO 2017176077 A1 WO2017176077 A1 WO 2017176077A1
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WO
WIPO (PCT)
Prior art keywords
microneedle
skin
metal
drug
present
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PCT/KR2017/003792
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French (fr)
Korean (ko)
Inventor
조성윤
김종택
추현욱
Original Assignee
랩앤피플주식회사
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Priority claimed from KR1020160162337A external-priority patent/KR20170115429A/en
Application filed by 랩앤피플주식회사 filed Critical 랩앤피플주식회사
Priority to ES17779377T priority Critical patent/ES2913153T3/en
Priority to US16/091,718 priority patent/US11135415B2/en
Priority to EP17779377.5A priority patent/EP3444003B1/en
Priority to PL17779377.5T priority patent/PL3444003T3/en
Priority to CN201780021995.1A priority patent/CN109069814A/en
Priority to BR112018070666A priority patent/BR112018070666A2/en
Priority to JP2019503883A priority patent/JP6794528B2/en
Priority to MX2018012236A priority patent/MX2018012236A/en
Publication of WO2017176077A1 publication Critical patent/WO2017176077A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • 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

Definitions

  • the present invention relates to an apparatus for delivering a drug to the body, and more particularly to a microneedle using a biodegradable metal and a microneedle patch comprising the same.
  • the microneedles When the microneedles are inserted into the skin, the microneedles must maintain a sufficiently high physical strength so that the microneedles can be inserted without being bent or broken.
  • stainless steel was used as the material of the microneedle, but inflammation occurred when small particles remained in the body, and polymers (PLA, PGA, and biodegradable copolymer) were used. There was a problem of not being penetration.
  • Korean Laid-Open Patent No. 2016-0058261 uses polyglycolide (PGA), polylactide-glycolide copolymer (PLGA), hyaluronic acid, alginic acid, pectin and the like.
  • PGA polyglycolide
  • PLGA polylactide-glycolide copolymer
  • hyaluronic acid alginic acid
  • pectin pectin and the like.
  • One water-soluble microneedle and a method of manufacturing the same have been disclosed
  • Korean Patent No. 1622388 discloses a silicon microneedle stamp and a method of manufacturing the same.
  • Korean Patent Application Publication No. 2015-0121053 discloses silicon, silicon dioxide, ceramics, and metals (stainless steel).
  • Titanium, nickel, molybdenum, chromium, cobalt and the like) and synthetic or natural resins have been disclosed.
  • the present inventors have made efforts to solve the above problems, as a result of using a microdegradable metal such as magnesium, calcium, zinc as the material of the microneedle, not only skin invasion is possible but also its own mineral components and hydrogen gas when left under the skin. It was confirmed that the supply can improve the skin by improving the wrinkle response and inflammatory response to complete the present invention.
  • a microdegradable metal such as magnesium, calcium, zinc
  • An object of the present invention is to solve the disadvantages of the existing drug delivery device, the pain causing and infection concerns, and medical waste, metal that can be used as a mineral for skin improvement while having physical properties that can penetrate the skin
  • the present invention provides a microneedle including a material and a microneedle patch including the same.
  • the present invention is represented by the formula (1), inserted into the subcutaneous or epithelium, absorbed and decomposed to release the magnesium or zinc metal ions and decomposition products in the body using a micro-degradable metal Serve the needle.
  • X is at least one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P
  • the biodegradable metal is characterized in that pure Mg or pure Zn containing inevitable impurities.
  • the biodegradable metal is characterized in that the decomposition rate is accelerated by creating a galvanic circuit of two or more metal phases.
  • the microneedle is characterized in that it comprises an Mg 2 Ca phase.
  • the microneedle is characterized in that it comprises an MgZn phase.
  • the microneedle is characterized in that it comprises a Ca 2 Mg 6 Zn 3 phase.
  • the microneedle is characterized in that a second kind of metal is coated on the metal surface to form a galvanic circuit.
  • the second metal is composed of sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver, gold, manganese and calcium It is characterized in that the at least one metal selected from the group.
  • the microneedle is characterized in that the drug is coated or supported.
  • the microneedle is characterized in that the thin plate-like.
  • the invention also provides a microneedle patch comprising the microneedle.
  • microneedle or microneedle patch to which the biodegradable metal of the present invention is applied can realize sufficient strength to penetrate the skin due to the metal's unique mechanical properties, and when inserted into the subcutaneous body to deliver the drug, By providing the generated decomposition products and gases to the skin, there is an effect that can swell the skin to improve wrinkles.
  • 1 to 3 is a state diagram according to the content of magnesium, zinc and calcium (circular number means an embodiment).
  • FIG. 4 is an exploded view of microneedles in which microneedles for penetrating skin and supporting drugs are formed on sheets composed of biodegradable metals.
  • 5 is a microneedle bent to machine the microneedle through the skin; It is a schematic diagram of the needle formed grooves on the outside of the needle and the grooves formed on the outside and inside to improve the drug carrying capacity.
  • FIG. 6 is a schematic diagram of a microneedle and microneedle holder in the form of a tip.
  • FIG. 7 is a prototype (A) of the microneedle manufactured according to an embodiment of the present invention (A) and a photograph (B) showing the stretching characteristics thereof.
  • FIG 8 is a photograph of a microneedle patch prepared according to one embodiment of the present invention (A: before use, B: after use).
  • FIG. 9 is a photograph of the microneedle prepared according to an embodiment of the present invention applied to the skin.
  • FIG. 10 is a schematic diagram of an apparatus (Eudiometer) for measuring the hydrogen generation amount according to the immersion time of the microneedle manufactured in accordance with an embodiment of the present invention.
  • FIG. 11 is a graph showing the hydrogen generation amount according to the immersion time of the microneedle prepared in accordance with an embodiment of the present invention.
  • FIG. 12 is a graph showing the results of a clinical experiment on the dermal density of the microneedle prepared in accordance with an embodiment of the present invention.
  • Figure 13 is a graph showing the results of clinical experiments on the skin thickness of the microneedle prepared in accordance with an embodiment of the present invention.
  • Figure 14 is a graph showing the results of clinical trials on the eye wrinkles of the microneedle prepared in accordance with an embodiment of the present invention.
  • Figure 15 is a photograph showing the results of clinical experiments on the eye wrinkles of the microneedle prepared in accordance with an embodiment of the present invention.
  • 16 is a photograph evaluating the polymer penetration capability of the microneedle patch prepared according to an embodiment of the present invention.
  • 17 is a photograph evaluating the drug penetration ability of the microneedle patch prepared according to an embodiment of the present invention.
  • the microneedle is made of at least one metal selected from the group consisting of Mg, Zn, Ca, Fe, Mn, Si, Na, Zr, Ce and P, not only skin invasion is possible but also subcutaneous. In addition, it did not cause inflammation, but rather to supply its own minerals to check that it can improve the skin.
  • a microneedle made of magnesium or zinc alone and a microneedle made of a biodegradable metal obtained by mixing another metal such as calcium with the metal, and invasiveness and skin improvement of the manufactured microneedle Ability was measured.
  • the microneedles made of magnesium, calcium or zinc as the sole material and the microneedles made of an alloy in which a different type of metal is mixed in the metal in a specific range have excellent invasiveness and skin improvement ability.
  • the present invention in one aspect, represented by the formula (1), is inserted into the subcutaneous or epithelium, absorbed and decomposed to release the magnesium or zinc metal ions and decomposition products in the body microneedle using a biodegradable metal It is about.
  • X is at least one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P
  • microneedles are used for the purpose of delivering drugs to the skin, but unlike the conventional microneedles, the microneedles are inserted into the subcutaneous or epithelium for drug injection, and then absorbed and decomposed to form metal ions and powders. It is characterized in that seafood is released into the body.
  • Magnesium (Mg), calcium (Ca), zinc (Zn) and the like used as the material of the microneedle of the present invention are alkali-based biodegradable metals, and a mechanism for releasing hydrogen gas by reacting with water as shown in the following formula.
  • the microneedle made of the metal material releases ions and decomposition products when absorbed and decomposed subcutaneously, and the hydrogen gas generated by the by-product can swell the subcutaneous effect and induce wrinkle improvement effect, and inflammation. It can reduce the erythema caused by skin and prevent skin damage caused by the sun (YOON, KS et al, Histological study on the effect of electrolyzed reduced water-bathing on UVB radiation-induced skin injury in hairless mice.
  • ZnO and MgCl may act as a drug delivery enhancer that enhances drug absorption even on the skin surface without penetrating subcutaneously. Therefore, the needle composed of the biodegradable metal can further enhance the drug delivery effect carried thereon.
  • the microneedles are made of magnesium (Mg), zinc (Zn) or the like as a single material, or two or more metals are used to accelerate the decomposition rate in the subcutaneous or epithelium, that is, to create a galvanic circuit. It can be manufactured as a material.
  • FIG. 1 to 3 is a state diagram according to the content of magnesium and zinc, calcium. As shown in Figures 1 to 3, magnesium, zinc and calcium may be present in various states depending on the content, Mg 2 Ca (C14_B) can create a galvanic circuit to increase the decomposition rate.
  • the microneedle is characterized in that a second kind of metal is coated on the surface of the biodegradable metal represented by Chemical Formula 1 to produce a galvanic circuit.
  • the second metal may include sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver, gold, manganese, calcium, and the like. It is not limited. At this time, when manufacturing the microneedle using the iron (Fe) should not include stainless.
  • the microneedles may be manufactured by a method of manufacturing conventional soluble microneedles in the industry, such as laser cutting, sheet metal processing, casting, etching, and the like, and the manufacturing method is not particularly limited.
  • the microneedle may be manufactured by bending in a jig press.
  • the microneedle is characterized in that the drug is coated or supported.
  • Fig. 5 shows the microneedle 11, in which the processed microneedle is bent to penetrate the skin; It is a schematic diagram of the needle (12) formed grooves on the outside of the needle and the needle (13) formed on the outside and inside to improve the drug carrying capacity.
  • the drug may include a drug or a genetic material for disease prevention and treatment, and may be loaded with EGF (Epitermal Growth Factor) or hyaluronic acid (Hyaluronic acid) for skin care.
  • EGF Epidermal Growth Factor
  • Hyaluronic acid Hyaluronic acid
  • the microneedles with biodegradable metal applied for drug loading can be coated by dip coating, and a pocket for drug delivery inside the microneedles can be formed to deliver drugs inside the body. Can be.
  • the pocket method when the pocket method is applied, a part of the drug contained in the microneedle patch is released immediately after attachment by controlling the rate of decomposition of the biodegradable metal, and the other drug decomposes the rate of drug release as the pocket formed on the biodegradable metal needle is decomposed. You can also adjust.
  • the microneedle according to the present invention may be formed in one piece or may be composed of the microneedle 20 and the microneedle holder 21 as shown in FIG. 6.
  • the microneedle utilizing the form of the microneedle holder 21 may be artificially left in the subcutaneously by applying a twist after the needle is inserted into the subcutaneous skin rather than simply injecting a drug to the skin.
  • FIG. 7 is a prototype (A) of the microneedle manufactured according to an embodiment of the present invention (A) and a photograph (B) showing the stretching characteristics thereof.
  • the present invention also relates to a microneedle patch comprising the microneedle.
  • the microneedle patch is for fixing the microneedle to the skin, and is composed of a microneedle and a patch portion formed on an opposite side of the microneedle.
  • the size, shape and material of the patch can be used without particular limitation.
  • the microneedles used may be ionized and discolored subcutaneously.
  • the drug After injecting the drug into the microneedle sheet, the drug may be injected subcutaneously through a slit generated in the microneedle by attaching to the skin and applying pressure.
  • a microneedle was manufactured using a laser marking machine (JTY FIBER MA20, JT Y System) (FIG. 9). At this time, the tip angles of the microneedles were 15 °, 30 °, and 35 °, and the needle heights were 0.5 mm, 1.0 mm, and 1.5 mm.
  • Skin invasiveness evaluation was performed on the microneedle of Example 1 having the lowest physical properties (tensile strength: average 212.09 MPa, elongation: 11.32%, self-retained material evaluation results) in Examples 1 to 9, and as a result Is shown in Table 2.
  • the skin invasiveness evaluation was performed whether the microneedles can invade the eyes and pig skin of the human body, whether the invasion is maintained for 1 minute or more after the invasion on the rough skin of the back of the human body (see Fig. 9).
  • Example 2 From Table 2, it was confirmed that the microneedle of Example 1 having a tip angle of 15 to 35 ° and a needle height of 0.5 to 1.5 mm was excellent in skin invasive ability, and the tensile strength was increased by adding calcium and zinc. It could be deduced that the microneedles of Examples 2 to 9 also have excellent skin invasiveness.
  • the microneedles of Examples 2 to 5 in which the Mg 2 Ca phase was not produced showed hydrogen gas generation amount due to stable decomposition, but the microneedles of Examples 6 and 7 in which the Mg 2 Ca phase was produced were decomposed. It was confirmed that the speed was increased.
  • the microneedle patch was prepared by attaching a hydrocolloid patch coated with an adhesive to the opposite side where the needle of the microneedle prepared in Example 1 was produced.
  • the prepared microneedle patch was packaged and sterilized.
  • the average age of 30 subjects was 39.47 years old, consisting of 6 in 20s, 5 in 30s, 18 in 40s and 1 in 50s.
  • Subject preliminary survey The subject survey was conducted.
  • -Skin condition Skin disease, itching, stinging, erythema, cosmetic side effects, side effects of medicine, light sensitivity, atopy experience
  • the visual evaluation of the tester was based on the Frosch & Kligman, CTFA guideline, and the skin reactivity was calculated and calculated as the skin irritation index. The degree was divided.
  • the microneedle patch was patched for 24 hours, and the skin reaction after 1 hour and 24 hours after patch removal was visually evaluated by the tester to determine the skin irritation index and the degree of skin irritation.
  • the dermal density increased by 8.67%
  • the skin thickness increased by 5.31%
  • the wrinkles on the eyes were decreased by 2.11% after two weeks of use, compared to the microneedle patch.
  • methylene blue dye was supported on the microneedle patch instead of the drug, and then attached to the pig skin. After attachment, the dye penetration was accelerated by continuous pressure for 5 minutes, and after 30 minutes, the microneedle patch was removed, the cross section of the pig skin was incised, and the drug delivery ability was evaluated by the optical microscope.
  • microneedle or the microneedle patch of the present invention can be used for drug delivery for skin prevention and disease prevention through vaccine delivery in addition to drug delivery for treatment.

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Abstract

The present invention relates to an apparatus for delivering a drug to a body and, more specifically, to a microneedle using a biodegradable metal and to a microneedle patch comprising the same. The microneedle is represented by chemical formula 1, and is absorbed and degraded after the subcutaneous or epithelial insertion to release metal ions and degraded products in the body. In chemical formula 1, a, b, and c represent weight percents of respective ingredients; a + b + c = 100 wt%; and a or b has the highest value in the ranges of 0 ≤ a ≤ 100, 0 ≤ b ≤ 100, and 0 ≤ c ≤ 10; and X is at least one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce, and P. The microneedle using a biodegradable metal of the present invention can realize sufficient strength to penetrate the skin due to unique mechanical characteristics of a metal. In addition, the microneedle is subcutaneously inserted to deliver a drug, and then provides the skin with degraded products and gas generated at the time of degradation as well as intrinsic minerals thereof, thereby allowing the skin to swell to ameliorate wrinkles. Therefore, the microneedle can be utilized for drug delivery for therapy, disease prevention through vaccine delivery, drug delivery for skin care, and the like.

Description

생체분해성 금속을 이용한 마이크로 니들Micro Needle Using Biodegradable Metal
본 발명은 신체에 약물을 전달하기 위한 장치에 관한 것으로, 더욱 상세하게는 생체분해성 금속을 이용한 마이크로 니들 및 이를 포함하는 마이크로니들 패치에 관한 것이다.The present invention relates to an apparatus for delivering a drug to the body, and more particularly to a microneedle using a biodegradable metal and a microneedle patch comprising the same.
종래의 약물 전달 방식은 경구 투여를 통한 방식 또는 바늘을 이용하여 피부에 구멍을 뚫어 약물을 전달하는 주사 방식이 사용되어 왔다. 그 중 효과적인 약물 전달 방식이라 할 수 있는 주사 방식은 주사기 사용 지식을 보유한 접종자가 필요하고, 주입시 고통을 수반하고 반복접종의 번거로움과 관리 소홀로 인한 바늘의 재사용으로 인해 감염이 발생할 수 있다. 또한, 사용된 주사기는 의료 폐기물로서 취급에 각별한 주의가 필요하게 된다. 최근 이러한 단점을 극복하기 위하여 피부에 분포한 통각 신경을 자극하지 않고 표피를 투과하여 약물을 전달할 수 있는 기기로서 마이크로 니들이 개발되었다. 마이크로 니들은 1998년 미국 조지아공대 프라우스니츠 그룹에서 반도체 공정기술을 이용하여 실리콘소자로 마이크로 니들 어레이를 만들어 약물전달에의 응용 가능성을 제시한 것을 시초로 많은 연구들이 활발하게 진행되고 있다. 마이크로 니들은 피부에 삽입할 때, 마이크로 니들이 구부러지거나 부러짐 없이 삽입될 수 있도록 충분히 높은 물리적 강도를 유지해야 하므로 그에 적합한 강도와 형상 제어가 가능한 특성이 요구된다. 이러한 특성을 만족시키기 위하여 마이크로 니들의 소재로 스테인레스 스틸(stainless steel)이 사용되었으나 작은 particle이 몸에 남을 경우 염증(inflammation)이 발생하는 문제가 있었고, 폴리머(PLA, PGA, 생분해성 Copolymer)의 경우 침습(penetration)이 되지 않는 문제점이 있었다.Conventional drug delivery methods have been used by oral administration or by injection method for puncturing the skin by using a needle. Among them, the injection method, which is an effective drug delivery method, requires an inoculator with knowledge of syringe usage, and infection may occur due to pain in the injection and reuse of the needle due to the hassle of repeated vaccinations and neglect of management. In addition, the syringe used is medical waste and requires special care in handling. Recently, microneedles have been developed as devices capable of delivering drugs through the epidermis without stimulating pain nerves distributed in the skin. Many researches have been actively conducted since the microneedles were proposed in 1998 by the Frausnits Group of Georgia Institute of Technology to make microneedle arrays of silicon devices using semiconductor process technology. When the microneedles are inserted into the skin, the microneedles must maintain a sufficiently high physical strength so that the microneedles can be inserted without being bent or broken. In order to satisfy these characteristics, stainless steel was used as the material of the microneedle, but inflammation occurred when small particles remained in the body, and polymers (PLA, PGA, and biodegradable copolymer) were used. There was a problem of not being penetration.
한국공개특허 제2016-0058261호는 폴리글리코라이드(PGA), 폴리락타이드-글리코라이드공중합체(PLGA), 히아루로닉 산(hyaluronic acid), 알지닉 산(alginic acid), 펙틴 등을 소재로 한 수용성 마이크로니들 및 이의 제조방법을 개시하였고, 한국등록특허 제1622388호는 실리콘 마이크로 니들 스탬프 및 그 제조방법을 개시하였고, 한국 공개특허 제2015-0121053호는 실리콘, 이산화규소, 세라믹, 금속(스테인리스, 티탄, 니켈, 몰리브덴, 크롬, 코발트 등) 및 합성 또는 천연의 수지를 소재로하여 일본 뇌염 백신 항원을 코팅시킨 마이크로 니들을 개시하였다. 하지만 이들은 앞서 설명한 바와 같이, 염증을 유발하거나 피부 침습이 되지 않는 문제점이 있다.Korean Laid-Open Patent No. 2016-0058261 uses polyglycolide (PGA), polylactide-glycolide copolymer (PLGA), hyaluronic acid, alginic acid, pectin and the like. One water-soluble microneedle and a method of manufacturing the same have been disclosed, and Korean Patent No. 1622388 discloses a silicon microneedle stamp and a method of manufacturing the same. Korean Patent Application Publication No. 2015-0121053 discloses silicon, silicon dioxide, ceramics, and metals (stainless steel). , Titanium, nickel, molybdenum, chromium, cobalt and the like) and synthetic or natural resins have been disclosed. However, as described above, there is a problem that does not cause inflammation or skin invasion.
이에, 본 발명자들은 상기 문제점들을 해결하기 위하여 노력한 결과, 마그네슘, 칼슘, 아연 등의 생체분해성 금속을 마이크로 니들의 소재로 사용할 경우 피부 침습이 가능할 뿐만 아니라 피하에 남을 경우 자체적인 미네랄 성분 및 수소가스를 공급하여 주름 개선 및 염증 반응을 개선하여 피부를 개선시킬 수 있다는 것을 확인하고, 본 발명을 완성하게 되었다.Therefore, the present inventors have made efforts to solve the above problems, as a result of using a microdegradable metal such as magnesium, calcium, zinc as the material of the microneedle, not only skin invasion is possible but also its own mineral components and hydrogen gas when left under the skin. It was confirmed that the supply can improve the skin by improving the wrinkle response and inflammatory response to complete the present invention.
본 발명의 목적은 기존의 약물 전달 기기의 단점인 통증 유발과 감염 우려 및 의료 폐기물에 대한 해결을 위한 것으로서, 피부를 관통할 수 있는 물리적 특성을 가지면서 피부 개선을 위한 미네랄로 이용될 수 있는 금속 소재를 포함하는 마이크로 니들 및 이를 포함하는 마이크로니들 패치를 제공하는데 있다. An object of the present invention is to solve the disadvantages of the existing drug delivery device, the pain causing and infection concerns, and medical waste, metal that can be used as a mineral for skin improvement while having physical properties that can penetrate the skin The present invention provides a microneedle including a material and a microneedle patch including the same.
상기 목적을 달성하기 위하여, 본 발명은 화학식 1로 표시되며, 피하 또는 상피에 삽입된 후 흡수 및 분해되어 마그네슘 또는 아연 금속 이온과 분해산물을 체내에 방출하는 것을 특징으로 하는 생체분해성 금속을 이용한 마이크로 니들을 제공한다.In order to achieve the above object, the present invention is represented by the formula (1), inserted into the subcutaneous or epithelium, absorbed and decomposed to release the magnesium or zinc metal ions and decomposition products in the body using a micro-degradable metal Serve the needle.
[화학식 1] [Formula 1]
MgaZnbXc Mg a Zn b X c
화학식 1에서 a, b 및 c는 각 성분의 중량%로서, a+b+c=100중량%이고, 0≤a≤100, 0≤b≤100, 0≤c≤10 범위중 a 또는 b가 가장 크며, X는 Ca, Fe, Mn, Si, Na, Zr, Ce 및 P로 구성된 군에서 선택되는 1종 이상임In Formula 1, a, b, and c are weight percents of each component, and a + b + c = 100 wt%, where a or b is in a range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, and 0 ≦ c ≦ 10. X is at least one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P
본 발명에 있어서, 상기 화학식 1의 a, b 및 c는 각 성분의 중량%로서, a+b+c=100중량%이고, i) 90≤a≤100, 0≤b≤10, 0≤c≤10 또는 ii) 0≤a≤10, 90≤b≤100, 0≤c≤10이며, X는 Ca, Fe, Mn, Si, Na, Zr, Ce 및 P로 구성된 군에서 선택되는 1종 이상인 것을 특징으로 한다. In the present invention, a, b and c in the formula (1) is a weight percent of each component, a + b + c = 100% by weight, i) 90≤a≤100, 0≤b≤10, 0≤c ≤ 10 or ii) 0 ≤ a ≤ 10, 90 ≤ b ≤ 100, 0 ≤ c ≤ 10, and X is at least one member selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P It is characterized by.
본 발명에 있어서, 상기 생체분해성 금속은 불가피한 불순물을 포함한 순수 Mg 또는 순수 Zn인 것을 특징으로 한다.In the present invention, the biodegradable metal is characterized in that pure Mg or pure Zn containing inevitable impurities.
본 발명에 있어서, 상기 생체분해성 금속은 2 이상의 금속 상(phase)이 갈바닉 회로를 생성하여 분해속도가 가속화되는 것을 특징으로 한다.In the present invention, the biodegradable metal is characterized in that the decomposition rate is accelerated by creating a galvanic circuit of two or more metal phases.
본 발명에 있어서, 상기 마이크로 니들은 Mg2Ca 상을 포함하는 것을 특징으로 한다.In the present invention, the microneedle is characterized in that it comprises an Mg 2 Ca phase.
본 발명에 있어서, 상기 마이크로 니들은 MgZn 상을 포함하는 것을 특징으로 한다.In the present invention, the microneedle is characterized in that it comprises an MgZn phase.
본 발명에 있어서, 상기 마이크로 니들은 Ca2Mg6Zn3 상을 포함하는 것을 특징으로 한다.In the present invention, the microneedle is characterized in that it comprises a Ca 2 Mg 6 Zn 3 phase.
본 발명에 있어서, 상기 마이크로 니들은 갈바닉 회로를 형성시키기 위하여 금속 표면에 다른 종류의 제2의 금속이 코팅된 것을 특징으로 한다.In the present invention, the microneedle is characterized in that a second kind of metal is coated on the metal surface to form a galvanic circuit.
본 발명에 있어서, 상기 제2의 금속은 나트륨, 마그네슘, 칼륨, 철, 니켈, 아연, 갈륨, 셀레늄, 스트론튬, 지르코늄, 몰리브덴, 니오븀, 탄탈륨, 타이타늄, 규소, 은, 금, 망간 및 칼슘으로 구성된 군에서 선택되는 1종 이상의 금속인 것을 특징으로 한다.In the present invention, the second metal is composed of sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver, gold, manganese and calcium It is characterized in that the at least one metal selected from the group.
본 발명에 있어서, 상기 마이크로 니들은 약물이 코팅되거나 담지되어 있는 것을 특징으로 한다.In the present invention, the microneedle is characterized in that the drug is coated or supported.
본 발명에 있어서, 상기 마이크로 니들은 박판 형인 것을 특징으로 한다.In the present invention, the microneedle is characterized in that the thin plate-like.
본 발명은 또한 상기 마이크로 니들을 포함하는 것을 특징으로 하는 마이크로 니들 패치를 제공한다. The invention also provides a microneedle patch comprising the microneedle.
본 발명의 생체분해성 금속을 적용한 마이크로 니들 또는 마이크로 니들 패치는 금속 특유의 기계적 특성으로 인해 피부를 관통할 수 있는 충분한 강도를 구현할 수 있고, 피하에 삽입되어 약물을 전달한 후, 자체 미네랄 뿐만 아니라 분해시 발생되는 분해산물과 가스를 피부에 제공함으로써, 피부에 팽윤을 주어 주름을 개선시킬 수 있는 효과가 있다. The microneedle or microneedle patch to which the biodegradable metal of the present invention is applied can realize sufficient strength to penetrate the skin due to the metal's unique mechanical properties, and when inserted into the subcutaneous body to deliver the drug, By providing the generated decomposition products and gases to the skin, there is an effect that can swell the skin to improve wrinkles.
도 1 내지 3은 마그네슘, 아연 및 칼슘의 함량에 따른 상태도이다(원형 숫자는 실시예를 의미함).1 to 3 is a state diagram according to the content of magnesium, zinc and calcium (circular number means an embodiment).
도 4는 생체분해성 금속으로 구성된 시트에 피부 관통과 약물 담지를 위한 마이크로 니들을 가공한 마이크로 니들의 전개도이다.FIG. 4 is an exploded view of microneedles in which microneedles for penetrating skin and supporting drugs are formed on sheets composed of biodegradable metals.
도 5는 가공된 마이크로 니들을 피부 관통을 위해 굽힘 가공한 마이크로 니들; 약물 담지 능력 향상을 위해 니들 외부에 홈을 형성한 니들 및 외부와 내부에 홈을 형성한 니들의 개략도이다.5 is a microneedle bent to machine the microneedle through the skin; It is a schematic diagram of the needle formed grooves on the outside of the needle and the grooves formed on the outside and inside to improve the drug carrying capacity.
도 6은 팁 형태의 마이크로 니들과 마이크로 니들 홀더의 개략도이다.6 is a schematic diagram of a microneedle and microneedle holder in the form of a tip.
도 7은 본 발명의 일 실시예에 따라 제조된 마이크로 니들의 시제품 사진(A) 및 이의 연신 특성을 나타낸 사진(B)이다.7 is a prototype (A) of the microneedle manufactured according to an embodiment of the present invention (A) and a photograph (B) showing the stretching characteristics thereof.
도 8은 본 발명의 일 실시예에 따라 제조된 마이크로 니들 패치의 사진이다(A: 사용 전, B: 사용 후).8 is a photograph of a microneedle patch prepared according to one embodiment of the present invention (A: before use, B: after use).
도 9는 본 발명의 일 실시예에 따라 제조된 마이크로 니들을 피부에 적용시킨 사진이다.9 is a photograph of the microneedle prepared according to an embodiment of the present invention applied to the skin.
도 10은 본 발명의 일 실시예에 따라 제조된 마이크로 니들의 침지시간에 따른 수소 발생량을 측정하는 장치(Eudiometer)의 개략도이다.10 is a schematic diagram of an apparatus (Eudiometer) for measuring the hydrogen generation amount according to the immersion time of the microneedle manufactured in accordance with an embodiment of the present invention.
도 11은 본 발명의 일 실시예에 따라 제조된 마이크로 니들의 침지시간에 따른 수소발생량을 나타낸 그래프이다. 11 is a graph showing the hydrogen generation amount according to the immersion time of the microneedle prepared in accordance with an embodiment of the present invention.
도 12는 본 발명의 일 실시예에 따라 제조된 마이크로 니들의 진피치밀도에 대한 임상실험 결과를 나타낸 그래프이다.12 is a graph showing the results of a clinical experiment on the dermal density of the microneedle prepared in accordance with an embodiment of the present invention.
도 13은 본 발명의 일 실시예에 따라 제조된 마이크로 니들의 피부두께에 대한 임상실험 결과를 나타낸 그래프이다.Figure 13 is a graph showing the results of clinical experiments on the skin thickness of the microneedle prepared in accordance with an embodiment of the present invention.
도 14는 본 발명의 일 실시예에 따라 제조된 마이크로 니들의 눈가주름에 대한 임상실험 결과를 나타낸 그래프이다.Figure 14 is a graph showing the results of clinical trials on the eye wrinkles of the microneedle prepared in accordance with an embodiment of the present invention.
도 15는 본 발명의 일 실시예에 따라 제조된 마이크로 니들의 눈가주름에 대한 임상실험 결과를 나타낸 사진이다.Figure 15 is a photograph showing the results of clinical experiments on the eye wrinkles of the microneedle prepared in accordance with an embodiment of the present invention.
도 16은 본 발명의 일 실시예에 따라 제조된 마이크로 니들 패치의 고분자 침투능을 평가한 사진이다. 16 is a photograph evaluating the polymer penetration capability of the microneedle patch prepared according to an embodiment of the present invention.
도 17은 본 발명의 일 실시예에 따라 제조된 마이크로 니들 패치의 약물 침투능을 평가한 사진이다. 17 is a photograph evaluating the drug penetration ability of the microneedle patch prepared according to an embodiment of the present invention.
본 발명에서는 Mg, Zn, Ca, Fe, Mn, Si, Na, Zr, Ce 및 P로 구성된 군에서 선택되는 1종 이상의 금속을 소재로 하여 마이크로 니들을 제조할 경우, 피부 침습이 가능할 뿐만 아니라 피하에 남아도 염증 유발을 하지 않고, 오히려 자체적인 미네랄 성분을 공급하여 피부를 개선시킬 수 있다는 것을 확인하고자 하였다. In the present invention, when the microneedle is made of at least one metal selected from the group consisting of Mg, Zn, Ca, Fe, Mn, Si, Na, Zr, Ce and P, not only skin invasion is possible but also subcutaneous. In addition, it did not cause inflammation, but rather to supply its own minerals to check that it can improve the skin.
본 발명에서는 마그네슘 또는 아연을 단독 소재로 한 마이크로 니들과 상기 금속에 칼슘 등의 다른 종류의 금속을 혼합한 생체분해성 금속을 소재로 한 마이크로 니들을 제조하고, 제조된 마이크로 니들의 침습능 및 피부개선능을 측정하였다. 그 결과 마그네슘, 칼슘 또는 아연을 단독 소재로 하여 제조된 마이크로 니들과 상기 금속에 다른 종류의 금속이 특정범위로 혼합된 합금으로 제조된 마이크로 니들은 침습능 및 피부개선능이 우수하다는 것을 확인할 수 있었다. In the present invention, a microneedle made of magnesium or zinc alone and a microneedle made of a biodegradable metal obtained by mixing another metal such as calcium with the metal, and invasiveness and skin improvement of the manufactured microneedle Ability was measured. As a result, it was confirmed that the microneedles made of magnesium, calcium or zinc as the sole material and the microneedles made of an alloy in which a different type of metal is mixed in the metal in a specific range have excellent invasiveness and skin improvement ability.
따라서, 본 발명은 일 관점에서, 화학식 1로 표시되며, 피하 또는 상피에 삽입된 후 흡수 및 분해되어 마그네슘 또는 아연 금속 이온과 분해산물을 체내에 방출하는 것을 특징으로 하는 생체분해성 금속을 이용한 마이크로 니들에 관한 것이다. Therefore, the present invention, in one aspect, represented by the formula (1), is inserted into the subcutaneous or epithelium, absorbed and decomposed to release the magnesium or zinc metal ions and decomposition products in the body microneedle using a biodegradable metal It is about.
[화학식 1] [Formula 1]
MgaZnbXc Mg a Zn b X c
화학식 1에서 a, b 및 c는 각 성분의 중량%로서, a+b+c=100중량%이고, 0≤a≤100, 0≤b≤100, 0≤c≤10 범위중 a 또는 b가 가장 크며, X는 Ca, Fe, Mn, Si, Na, Zr, Ce 및 P로 구성된 군에서 선택되는 1종 이상임In Formula 1, a, b, and c are weight percents of each component, and a + b + c = 100 wt%, where a or b is in a range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, and 0 ≦ c ≦ 10. X is at least one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P
상기 마이크로 니들은 마그네슘 또는 아연을 가장 많이 포함하는 것이 바람직하다. 따라서, 상기 화학식 1에서 a, b 및 c는 각 성분의 중량%로서, a+b+c=100중량%이고, i) 90≤a≤100, 0≤b≤10, 0≤c≤10 또는 ii) 0≤a≤10, 90≤b≤100, 0≤c≤10이며, X는 Ca, Fe, Mn, Si, Na, Zr, Ce 및 P로 구성된 군에서 선택되는 1종 이상인 것을 특징으로 한다.The microneedles preferably contain the most magnesium or zinc. Accordingly, in Formula 1, a, b and c are weight percent of each component, and a + b + c = 100 wt%, i) 90 ≦ a ≦ 100, 0 ≦ b ≦ 10, 0 ≦ c ≦ 10 or ii) 0 ≦ a ≦ 10, 90 ≦ b ≦ 100, 0 ≦ c ≦ 10, and X is at least one member selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce, and P do.
통상적으로 마이크로 니들은 약물을 피부에 전달하기 위한 목적으로 사용되지만 본 발명에 따른 마이크로 니들은 통상적인 마이크로 니들과는 달리 약물 주입을 위하여 피하 또는 상피에 삽입된 후, 흡수 및 분해되어 금속 이온 및 분해산물을 체내에 방출되는 것을 특징으로 한다.Typically, microneedles are used for the purpose of delivering drugs to the skin, but unlike the conventional microneedles, the microneedles are inserted into the subcutaneous or epithelium for drug injection, and then absorbed and decomposed to form metal ions and powders. It is characterized in that seafood is released into the body.
본 발명의 마이크로 니들의 소재로 사용되는 마그네슘(Mg), 칼슘(Ca), 아연(Zn) 등은 알카리토금속 계열의 생체분해성 금속으로서, 하기의 수식과 같이 물과 반응하여 수소가스를 방출하는 메커니즘을 갖는다. 따라서, 상기 금속을 소재로 한 마이크로 니들은 피하에서 흡수, 분해시 이온 및 분해산물을 방출하며, 부산물로 인해 생성되는 수소 가스가 피하 내에서 팽윤효과를 주어 주름 개선 효과를 유도할 수 있고, 염증에 의한 피부 홍반을 감소시키는 효과와 태양으로 인해 야기되는 피부손상을 방지할 수 있다(YOON, K. S. et al, Histological study on the effect of electrolyzed reduced water-bathing on UVB radiation-induced skin injury in hairless mice. Biological and Pharmaceutical Bulletin 34, 1671-7, 2011; IGNACIO, R. M., et al, The balneotherapy effect of hydrogen reduced water on UVB-mediated skin injury in hairless mice. Molecular & Cellular Toxicology 9, 15-21, 2013).Magnesium (Mg), calcium (Ca), zinc (Zn) and the like used as the material of the microneedle of the present invention are alkali-based biodegradable metals, and a mechanism for releasing hydrogen gas by reacting with water as shown in the following formula. Has Therefore, the microneedle made of the metal material releases ions and decomposition products when absorbed and decomposed subcutaneously, and the hydrogen gas generated by the by-product can swell the subcutaneous effect and induce wrinkle improvement effect, and inflammation. It can reduce the erythema caused by skin and prevent skin damage caused by the sun (YOON, KS et al, Histological study on the effect of electrolyzed reduced water-bathing on UVB radiation-induced skin injury in hairless mice. Biological and Pharmaceutical Bulletin 34, 1671-7, 2011; IGNACIO, RM, et al, The balneotherapy effect of hydrogen reduced water on UVB-mediated skin injury in hairless mice.Molecular & Cellular Toxicology 9, 15-21, 2013).
마그네슘(Mg)과 아연(Zn)이 생체 내에 삽입되어 생성되는 부산물인 ZnO 및 MgCl은 피하에 침투하지 않고 피부 표면에만 있어도 약물 흡수를 향상시키는 약물 전달 강화제(Drug delivery enhancer)로서 역할이 가능하다. 따라서, 생체분해성 금속으로 구성된 니들은 자체에 담지하고 있는 약물 전달 효과를 더욱 상승시킬 수 있다.By-products produced by the insertion of magnesium (Mg) and zinc (Zn) in vivo, ZnO and MgCl may act as a drug delivery enhancer that enhances drug absorption even on the skin surface without penetrating subcutaneously. Therefore, the needle composed of the biodegradable metal can further enhance the drug delivery effect carried thereon.
Mg + 2H2O → Mg(OH)2 + H2 (gas)Mg + 2H 2 O → Mg (OH) 2 + H 2 (gas)
Ca + 2H2O → Ca(OH)2 + H2 (gas)Ca + 2H 2 O → Ca (OH) 2 + H 2 (gas)
Zn + H2O → Zn(OH)2 + H2 (gas)Zn + H 2 O → Zn (OH) 2 + H 2 (gas)
본 발명에 있어서, 상기 마이크로 니들은 마그네슘(Mg), 아연(Zn) 등을 단독 소재로 하여 제조되거나, 피하 또는 상피에서의 분해속도를 가속화시키기 위하여, 즉 갈바닉 회로를 생성시키기 위하여 2 이상의 금속을 소재로 하여 제조될 수 있다. In the present invention, the microneedles are made of magnesium (Mg), zinc (Zn) or the like as a single material, or two or more metals are used to accelerate the decomposition rate in the subcutaneous or epithelium, that is, to create a galvanic circuit. It can be manufactured as a material.
도 1~3은 마그네슘과 아연, 칼슘의 함량에 따른 상태도이다. 도 1~3에 도시된 바와 같이, 마그네슘, 아연 및 칼슘은 그 함량에 따라 다양한 상태로 존재할 수 있는데, Mg2Ca(C14_B)는 갈바닉 회로를 생성하여 분해속도를 증진시킬 수 있다.1 to 3 is a state diagram according to the content of magnesium and zinc, calcium. As shown in Figures 1 to 3, magnesium, zinc and calcium may be present in various states depending on the content, Mg 2 Ca (C14_B) can create a galvanic circuit to increase the decomposition rate.
본 발명에 있어서, 상기 마이크로 니들은 갈바닉 회로를 생성하기 위하여 상기 화학식 1로 표시되는 생체분해성 금속 표면에 다른 종류의 제2의 금속이 코팅된 것을 특징으로 한다. 상기 제2의 금속은 나트륨, 마그네슘, 칼륨, 철, 니켈, 아연, 갈륨, 셀레늄, 스트론튬, 지르코늄, 몰리브덴, 니오븀, 탄탈륨, 타이타늄, 규소, 은, 금, 망간, 칼슘 등을 예시할 수 있으나 이에 한정되는 것은 아니다. 이때, 상기 철(Fe)을 이용하여 마이크로 니들을 제조시에는 스테인레스가 포함되지 않아야 한다.In the present invention, the microneedle is characterized in that a second kind of metal is coated on the surface of the biodegradable metal represented by Chemical Formula 1 to produce a galvanic circuit. The second metal may include sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver, gold, manganese, calcium, and the like. It is not limited. At this time, when manufacturing the microneedle using the iron (Fe) should not include stainless.
본 발명에 있어서, 마이크로 니들은 레이저 커팅, 판금 공정, 캐스팅 공법, 에칭 공법 등 업계의 통상적인 용해성 마이크로니들을 제조하는 방법으로 제조될 수 있으며, 제조방법은 특별히 제한되지 않는다. 예를 들어 도 4와 같이 생체분해성 금속으로 구성된 박판형 시트(10)를 제조한 후 레이저 커팅기(마킹기)를 이용하여 일정 형태로 성형 후, 지그 프레스로 벤딩함으로써 마이크로 니들을 제조할 수 있다. In the present invention, the microneedles may be manufactured by a method of manufacturing conventional soluble microneedles in the industry, such as laser cutting, sheet metal processing, casting, etching, and the like, and the manufacturing method is not particularly limited. For example, after manufacturing the thin sheet 10 made of a biodegradable metal as shown in FIG. 4 and then molded in a certain shape using a laser cutting machine (marker), the microneedle may be manufactured by bending in a jig press.
상기 마이크로 니들은 약물이 코팅되거나 담지되어 있는 것을 특징으로 한다. 도 5는 가공된 마이크로 니들을 피부 관통을 위해 굽힘 가공한 마이크로 니들(11); 약물 담지 능력 향상을 위해 니들 외부에 홈을 형성한 니들(12) 및 외부와 내부에 홈을 형성한 니들(13)의 개략도이다.The microneedle is characterized in that the drug is coated or supported. Fig. 5 shows the microneedle 11, in which the processed microneedle is bent to penetrate the skin; It is a schematic diagram of the needle (12) formed grooves on the outside of the needle and the needle (13) formed on the outside and inside to improve the drug carrying capacity.
상기 약물은 질병 예방과 치료를 위한 약물 또는 유전자 물질을 포함할 수 있으며, 피부미용을 위한 EGF(Epidermal Growth Factor: 상피세포 성장인자)나 히알루론산(Hyaluronic acid)이 담지될 수 있다. 약물 담지를 위해 제작된 생체분해성 금속을 적용한 마이크로 니들을 침지하는 방식(dip coating)으로 코팅할 수 있으며, 마이크로 니들 내부에 약물을 담지할 수 있는 포켓(pocket)을 성형하여 약물을 신체 내부에 전달할 수 있다. 이때 포켓 방식을 적용할 경우 생체분해성 금속의 분해 속도를 조절하여 마이크로 니들 패치에 담지 된 약물의 일부는 부착 즉시 방출하고, 나머지 약물은 생체분해성 금속 니들에 성형된 포켓이 분해되면서 약물 방출의 속도를 조절할 수도 있다.The drug may include a drug or a genetic material for disease prevention and treatment, and may be loaded with EGF (Epitermal Growth Factor) or hyaluronic acid (Hyaluronic acid) for skin care. The microneedles with biodegradable metal applied for drug loading can be coated by dip coating, and a pocket for drug delivery inside the microneedles can be formed to deliver drugs inside the body. Can be. In this case, when the pocket method is applied, a part of the drug contained in the microneedle patch is released immediately after attachment by controlling the rate of decomposition of the biodegradable metal, and the other drug decomposes the rate of drug release as the pocket formed on the biodegradable metal needle is decomposed. You can also adjust.
본 발명에 따른 마이크로 니들은 일체형으로 구성되거나 도 6과 같이 마이크로 니들(20)과 마이크로 니들 홀더(21)로 구성될 수 있다. 마이크로 니들 홀더(21)형태를 활용한 마이크로 니들은 단순히 피부에 접근하여 약물을 주입만이 아닌 피하에 니들이 삽입 된 후 비틀림을 가하여 인위적으로 니들이 피하에 잔존하도록 할 수도 있다.The microneedle according to the present invention may be formed in one piece or may be composed of the microneedle 20 and the microneedle holder 21 as shown in FIG. 6. The microneedle utilizing the form of the microneedle holder 21 may be artificially left in the subcutaneously by applying a twist after the needle is inserted into the subcutaneous skin rather than simply injecting a drug to the skin.
도 7은 본 발명의 일 실시예에 따라 제조된 마이크로 니들의 시제품 사진(A) 및 이의 연신 특성을 나타낸 사진(B)이다.7 is a prototype (A) of the microneedle manufactured according to an embodiment of the present invention (A) and a photograph (B) showing the stretching characteristics thereof.
본 발명은 또한, 상기 마이크로 니들을 포함하는 것을 특징으로 하는 마이크로 니들 패치에 관한 것이다.The present invention also relates to a microneedle patch comprising the microneedle.
도 8에 도시된 바와 같이, 상기 마이크로 니들 패치는 마이크로 니들을 피부에 고정시키기 위한 것으로서, 마이크로 니들 및 상기 마이크로 니들의 반대 면에 형성된 패치부로 구성되어 있다. 상기 패치부의 크기, 모양 및 소재는 특별한 제한없이 이용 가능하다. 도 8의 B에 도시된 바와 같이, 사용된 마이크로 니들은 피하에서 이온화되어 변색될 수 있다.As shown in FIG. 8, the microneedle patch is for fixing the microneedle to the skin, and is composed of a microneedle and a patch portion formed on an opposite side of the microneedle. The size, shape and material of the patch can be used without particular limitation. As shown in FIG. 8B, the microneedles used may be ionized and discolored subcutaneously.
상기 마이크로 니들 시트에 약물을 주입한 후, 피부에 부착시키고 압력을 가하게 되면 마이크로 니들에 생성된 슬릿(slit)을 통하여 약물이 피하에 주입될 수 있다.After injecting the drug into the microneedle sheet, the drug may be injected subcutaneously through a slit generated in the microneedle by attaching to the skin and applying pressure.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다. Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.
실시예 1~9: 마그네슘 또는 아연을 주 소재로 제조한 마이크로 니들Examples 1 to 9 microneedle made of magnesium or zinc as the main material
하기 표 1의 조성(중량%)으로 시트를 제작한 후, 레이저 마킹기(JTY FIBER MA20, 제이티와이시스템)를 이용하여 마이크로 니들을 제조하였다(도 9). 이때, 마이크로 니들의 선단각은 15°, 30° 및 35°로 하였고, 니들 높이는 0.5㎜, 1.0㎜ 및 1.5㎜로 하였다.After preparing the sheet in the composition (wt%) of Table 1, a microneedle was manufactured using a laser marking machine (JTY FIBER MA20, JT Y System) (FIG. 9). At this time, the tip angles of the microneedles were 15 °, 30 °, and 35 °, and the needle heights were 0.5 mm, 1.0 mm, and 1.5 mm.
실시예Example MgMg CaCa ZnZn
1One 99.99*99.99 * -- --
22 98.3598.35 0.050.05 1.601.60
33 98.9598.95 0.050.05 1.001.00
44 98.998.9 0.100.10 1.001.00
55 98.8598.85 0.150.15 1.001.00
66 96.996.9 0.100.10 3.003.00
77 96.8596.85 0.150.15 3.003.00
88 0.000.00 0.000.00 99.99*99.99 *
99 10.0010.00 0.000.00 90.0090.00
* 제조시 발생되는 불가피한 불순물을 포함한 순수 금속* Pure metals containing unavoidable impurities generated during manufacturing
실험예 1: 마이크로 니들의 피부 침습능 평가Experimental Example 1: Evaluation of Skin Invasiveness of the Microneedle
실시예 1~9에서 가장 낮은 물리적 특성(인장강도: 평균 212.09MPa, 연신율: 11.32%, 자체 보유 소재 평가 결과)을 가지는 실시예 1의 마이크로 니들을 대상으로 피부 침습능 평가를 수행하고, 그 결과를 표 2에 나타내었다. 상기 피부 침습능 평가는 마이크로 니들이 인체의 눈가 및 돼지 피부에 침습 가능한지, 인체 부위 중 거친 손등 피부 위에 침습 후 1분 이상 침습이 유지되는지 여부를 수행하였다(도 9 참조). Skin invasiveness evaluation was performed on the microneedle of Example 1 having the lowest physical properties (tensile strength: average 212.09 MPa, elongation: 11.32%, self-retained material evaluation results) in Examples 1 to 9, and as a result Is shown in Table 2. The skin invasiveness evaluation was performed whether the microneedles can invade the eyes and pig skin of the human body, whether the invasion is maintained for 1 minute or more after the invasion on the rough skin of the back of the human body (see Fig. 9).
니들 높이(mm)Needle height (mm) 선단각(°)Tip angle (°) 니들간 간격(mm)Distance between needles (mm) 피부 침습능Skin invasiveness
0.50.5 1515 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
3030 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
3535 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
1.01.0 1515 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
3030 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
3535 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
1.51.5 1515 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
3030 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
3535 1.01.0 피부 침습 후 유지Keep after skin invasion
1.21.2 피부 침습 후 유지Keep after skin invasion
1.51.5 피부 침습 후 유지Keep after skin invasion
2.02.0 피부 침습 후 유지Keep after skin invasion
표 2로부터, 선단각이 15~35°이고, 니들 높이가 0.5~1.5㎜인 실시예 1의 마이크로 니들은 피부 침습능이 우수하다는 것을 확인할 수 있었고, 칼슘 및 아연이 추가되어 인장강도가 증가된 실시예 2 내지 9의 마이크로 니들 또한 피부 침습능이 우수하다는 것을 유추할 수 있었다. From Table 2, it was confirmed that the microneedle of Example 1 having a tip angle of 15 to 35 ° and a needle height of 0.5 to 1.5 mm was excellent in skin invasive ability, and the tensile strength was increased by adding calcium and zinc. It could be deduced that the microneedles of Examples 2 to 9 also have excellent skin invasiveness.
실험예 2: 마이크로 니들의 분해속도 평가Experimental Example 2: Evaluation of the decomposition rate of the microneedle
실시예 2 내지 7에서 제조된 마이크로 니들을 표 3의 조성을 갖는 생체 모사용액을 포함하는 유디오미터(Eudiometer)에 침지시킨 후(도 10 참조), 침지시간에 따른 수소 발생량으로 분해속도를 평가하고 그 결과를 도 11에 나타내었다.After immersing the microneedles prepared in Examples 2 to 7 in an edometer (Eudiometer) containing a biological mother liquor having a composition of Table 3 (see FIG. 10), the decomposition rate was evaluated by the amount of hydrogen generated according to the immersion time The results are shown in FIG.
성분ingredient 몰농도[mM/L]Molarity [mM / L] 질량[g]Mass [g]
CaCl2·2H2OCaCl 2 · 2H 2 O 1.261.26 0.1850.185
KClKCl 5.375.37 0.4000.400
KH2PO4 KH 2 PO 4 0.440.44 0.0600.060
MgSO4·H2OMgSO 4 H 2 O 0.810.81 0.2000.200
NaClNaCl 136.89136.89 8.0008.000
Na2HPO4·2H2ONa 2 HPO 4 2H 2 O 0.340.34 0.0600.060
NaHCO3 NaHCO 3 4.174.17 0.3500.350
D-GlucoseD-Glucose 5.555.55 1.0001.000
도 11에 나타난 바와 같이, Mg2Ca 상이 생성되지 않는 실시예 2 내지 5의 마이크로 니들은 안정적인 분해에 따른 수소가스 발생량을 보였으나, Mg2Ca 상이 생성되는 실시예 6 및 7의 마이크로 니들은 분해속도가 상승되었음을 확인할 수 있었다. As shown in FIG. 11, the microneedles of Examples 2 to 5 in which the Mg 2 Ca phase was not produced showed hydrogen gas generation amount due to stable decomposition, but the microneedles of Examples 6 and 7 in which the Mg 2 Ca phase was produced were decomposed. It was confirmed that the speed was increased.
실시예 10: 마이크로 니들 패치의 제조Example 10 Preparation of Microneedle Patches
실시예 1에서 제조된 마이크로 니들의 바늘이 생성된 반대쪽 면에 접착제가 도포된 하이드로 콜로이드 패치를 부착하여 마이크로 니들 패치를 제조하였다. 제조된 마이크로 니들 패치는 포장 및 멸균시켰다.The microneedle patch was prepared by attaching a hydrocolloid patch coated with an adhesive to the opposite side where the needle of the microneedle prepared in Example 1 was produced. The prepared microneedle patch was packaged and sterilized.
실험예 3: 마이크로 니들 패치의 피부 자극평가Experimental Example 3: Evaluation of skin irritation of the microneedle patch
실시예 10에서 제조된 마이크로 니들 패치의 인체 피부에 대한 일차자극 유무를 확인하기 위하여 피부임상연구센터에 평가를 의뢰하였다.In order to confirm whether the microneedle patch prepared in Example 10 had primary stimulation on human skin, an evaluation was requested to the skin clinical research center.
<시험방법><Test method>
(1) 시험물질 적용부위(1) Application area of test substance
- 시험대상자의 척추를 제외한 등의 평평한 부위로 착색이나 피부손상이 없는 부위-A flat area, except the spine of the subject, with no pigmentation or skin damage
(2) 시험물질 적용 전(2) Before applying test substance
- 시험부위의 사진촬영 및 시험대상자 피부조건에 대한 설문평가 등을 실시하였다.-Photographs of the test site and questionnaire evaluation were conducted on the skin conditions of the test subjects.
(3) 시험물질 적용(3) Application of test substance
- IQ chamber에 20㎕ loading하고 피부에 밀착시킨 후 3M Micropore Tape로 고정하였다.-20μL loaded into the IQ chamber and adhered to the skin and fixed with 3M Micropore Tape.
- 시험물질을 적용한 IQ chamber는 시험부위에 24시간동안 적용하였다.-IQ chamber with test material was applied to test site for 24 hours.
- 24시간 후 IQ chamber를 제거하고 1시간 후 시험물질 적용부위의 사진촬영 및 시험자에 의한 피부반응 정도를 평가하였다.-After 24 hours, the IQ chamber was removed, and after 1 hour, photographs of the test substance application site and the degree of skin reaction by the tester were evaluated.
- IQ chamber 제거 후 24시간에 시험물질 적용부위의 사진촬영 및 시험자에 의한 피부반응 정도를 평가하였다.-24 hours after removal of the IQ chamber, photographs of the test substance application site and the degree of skin reaction by the tester were evaluated.
(4) 시험 대상자(4) Test subject
시험대상자 30명의 평균 연령은 만 39.47세로 20대 6명, 30대 5명, 40대 18명, 50대 1명으로 구성되었으며 성별은 남성 3명, 여성 27명이었다.The average age of 30 subjects was 39.47 years old, consisting of 6 in 20s, 5 in 30s, 18 in 40s and 1 in 50s.
<평가방법><Evaluation Method>
(1) 시험대상자 사전조사 : 시험대상자 설문으로 조사하였다.(1) Subject preliminary survey: The subject survey was conducted.
- 피부상태 : 건성, 중건성, 중성, 중지성, 지성, 문제성 피부의 해당 여부-Skin condition: Whether dry, neutral, neutral, middle to oily, oily or problematic skin
- 피부조건 : 피부질환, 가려움, 따가움, 홍반, 화장품부작용, 의약품 부작용, 광 민감성, 아토피경험-Skin condition: Skin disease, itching, stinging, erythema, cosmetic side effects, side effects of medicine, light sensitivity, atopy experience
(2) 평가항목(2) Evaluation item
- 시험자 육안평가 : 시험물질 적용부위에 나타나는 피부자극의 정도-Visual assessment of the tester: The degree of skin irritation at the site of application of the test substance
(3) 피부자극정도 평가방법(3) Evaluation method of skin irritation degree
-시험자 육안평가는 Frosch & Kligman, CTFA guideline에 근거하여 피부반응도를 판독하고, 피부자극지수로 산출하였으며, Draize 방법을 응용하여 생성된 피부자극 지수표(표 4)를 참조하여 시험 물질의 피부자극 정도를 구분하였다.-The visual evaluation of the tester was based on the Frosch & Kligman, CTFA guideline, and the skin reactivity was calculated and calculated as the skin irritation index. The degree was divided.
피부자극 지수Skin irritation index 구분division
0.00~0.250.00-0.25 비(무) 자극성Non-irritant
0.26~1.000.26-1.00 약한 자극성Mild irritant
1.01~2.501.01-2.50 중등도 자극성Moderate irritant
2.51~4.002.51-4.00 강한 자극성Strong irritant
마이크로니들 패치를 24시간 첩포하고, 첩포 제거 1시간, 24시간 후의 피부반응을 시험자가 육안으로 평가하여 피부자극지수 및 피부 자극 정도를 판정한 결과, 약한 자극성으로 판정되었다(표 5).The microneedle patch was patched for 24 hours, and the skin reaction after 1 hour and 24 hours after patch removal was visually evaluated by the tester to determine the skin irritation index and the degree of skin irritation.
시험제품Test Product 피부자극지수Skin irritation index 피부자극정도 Skin irritation degree
1시간후1 hour later 24시간후24 hours later 종합Synthesis
마이크로 니들 패치Micro needle patch 0.930.93 0.330.33 0.630.63 약한 자극성Mild irritant
실험예 4: 마이크로 니들 패치의 임상평가Experimental Example 4: Clinical Evaluation of the Microneedle Patch
실시예 10에서 제조된 마이크로 니들 패치의 임상평가를 수행하였다. 선정기준에 부합하고 선정제외기준에 해당하지 않는 눈가주름을 보유한 만 29~55세의 여성 20명의 시험자에게 마이크로 니들 패치를 적용시킨 후, 사용전과 사용 2주 후의 진피치밀도, 피부두께 및 눈가주름의 변화유무를 확인하고, 그 결과의 평균치를 도 12~14에 나타내었다.Clinical evaluation of the microneedle patch prepared in Example 10 was performed. After applying the microneedle patch to 20 test subjects aged 29-55 years old who meet the selection criteria and do not meet the exclusion criteria, the dermal density, skin thickness and wrinkles before and after 2 weeks of use The change was confirmed and the average value of the result is shown in FIGS.
※ 선정기준※ Selection criteria
1. 눈가주름을 보유한 여성1. Women with eye wrinkles
2. 시험책임자 또는 시험책임자의 위임을 받은 사람이 시험대상자에게 알려주어야 할 사항에 대하여 충분히 설명을 듣고 자발적으로 동의서를 작성하고 서명한 자 2. A person who has been fully informed and informed of what the examiner or the person in charge of the investigator should inform the subject, and has voluntarily completed and signed the agreement.
3. 피부 질환을 포함하는 급, 만성 신체질환이 없는 건강한 자3. Healthy person without grade or chronic physical disease including skin disease
4. 시험기간 동안 추적 관찰이 가능한 자4. Anyone who can follow up during the trial
※ 선정 제외 기준※ Selection Exclusion Criteria
1. 정신과적 질환이 있는 사람1. a person with a psychiatric illness
2. 감염성 피부질환이 있는 사람2. People with infectious skin disease
3. 시험 시작 전 3개월 내에 면역억제제 치료를 받은 사람3. Those who received immunosuppressive treatment within 3 months before starting the test
4. 시험 시작 전 1개월 내에 전신 스테로이드 또는 광선치료를 받은 사람4. Anyone who received systemic steroids or phototherapy within one month prior to the start of the study
5. 시험부위에 병변이 있어 측정이 곤란한 사람5. Person who has difficulty in measuring because of lesion on test site
진피치밀도, 피부두께 및 눈가주름의 측정방법은 하기 표 6 및 표 7과 같다.Dermal pitch density, skin thickness and eye wrinkle measurement methods are shown in Tables 6 and 7.
진피치밀도 및 피부두께 측정 방법How to measure dermal density and skin thickness
시험방법Test Methods Skin scanner 측정Skin scanner measurement
시험부위Test site 눈가Snow
측정구간Measurement section 사용전, 사용 2주후Before use, 2 weeks after use
DATADATA 수치제공Figures
비고Remarks 얼굴좌측 : 마이크로 니들 패치 + 세럼얼굴우측 : 마이크로 니들 패치Face Left: Micro Needle Patch + Serum Face Right: Micro Needle Patch
눈가주름 측정 방법How to measure eye wrinkles
시험방법Test Methods Primos premium 촬영 후 Ra 분석Ra analysis after Primos premium
시험부위Test site 눈가Snow
측정구간Measurement section 사용전, 사용 2주후Before use, 2 weeks after use
DATADATA 수치/이미지 제공Provide figures / images
비고Remarks 얼굴좌측 : 마이크로 니들 패치 + 세럼얼굴우측 : 마이크로 니들 패치Face Left: Micro Needle Patch + Serum Face Right: Micro Needle Patch
※ 측정 조건 : 항온 항습 조건에서 측정※ Measurement condition: measured under constant temperature and humidity
그 결과, 도 12~14에 도시된 바와 같이, 마이크로 니들 패치 사용 전에 비하여 사용 2주 후 진피치밀도는 8.67% 증가하였고, 피부두께는 5.31% 증가하였고, 눈가주름은 2.11% 감소하였다. 또한, 도 15의 사진으로부터도, 눈가의 주름이 확연하게 감소된 것을 확인할 수 있었다.As a result, as shown in FIGS. 12 to 14, the dermal density increased by 8.67%, the skin thickness increased by 5.31%, and the wrinkles on the eyes were decreased by 2.11% after two weeks of use, compared to the microneedle patch. In addition, it was confirmed from the photograph of FIG. 15 that the wrinkles around the eyes were significantly reduced.
실험예 5: 마이크로 니들 시트의 약물전달 평가Experimental Example 5: Evaluation of Drug Delivery of Micro Needle Sheet
5-1: 고분자 피부 침투능 평가5-1: Evaluation of polymer skin penetration
실시예 10에서 제조된 마이크로 니들 패치의 고분자 피부 전달능을 평가하기 위하여 립스틱을 피부에 바르고, 마이크로 니들 패치를 부착하고 30분 후, 패치를 제거하고 씻어냈다. 참고로 500da 이상의 분자량을 갖는 물질들은 피부에 잘 흡수되지 않는 특성이 있다.To evaluate the polymer skin delivery ability of the microneedle patch prepared in Example 10, a lipstick was applied to the skin, and 30 minutes after the microneedle patch was attached, the patch was removed and washed off. For reference, substances having a molecular weight of 500 da or more have a property of being poorly absorbed by the skin.
그 결과, 도 16에 도시된 바와 같이 마이크로 니들 패치를 부착하지 않은 경우, 립스틱이 흡수되지 않아 씻겨나갔지만, 마이크로 니들 패치를 부착시킨 경우에는 립스틱이 피부에 흡수되었음을 확인할 수 있었다.As a result, when the microneedle patch was not attached as shown in FIG. 16, the lipstick was not absorbed and washed away, but when the microneedle patch was attached, the lipstick was confirmed to be absorbed into the skin.
5-2: 돼지 스킨을 이용한 약물 전달 평가5-2: Drug Delivery Evaluation Using Pig Skin
실시예 10에서 제조된 마이크로 니들 패치의 약물 피부 전달능을 평가하기 위하여 약물을 대신하여 메틸렌 블루 염료를 마이크로 니들 패치에 담지한 후, 돼지 스킨에 부착시켰다. 부착 후, 5분간 지속적인 압력을 가하여 염료 침투를 가속화 시켰으며, 30분 후 마이크로 니들 패치를 제거한 후, 돼지 스킨의 단면을 절개한 후 광학 현미경으로 약물 전달능을 평가하였다.In order to evaluate the drug skin delivery ability of the microneedle patch prepared in Example 10, methylene blue dye was supported on the microneedle patch instead of the drug, and then attached to the pig skin. After attachment, the dye penetration was accelerated by continuous pressure for 5 minutes, and after 30 minutes, the microneedle patch was removed, the cross section of the pig skin was incised, and the drug delivery ability was evaluated by the optical microscope.
도 17에 도시된 바와 같이, 마이크로 니들이 침투한 곳에는 염료가 진하게 침착된 것을 확인할 수 있었다.As shown in FIG. 17, it was confirmed that the dye was thickly deposited where the microneedles penetrated.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적 기술은 단지 바람직한 실시 양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.As described above in detail specific parts of the present invention, it will be apparent to those skilled in the art that these specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. will be. Thus, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
본 발명의 마이크로 니들 또는 마이크로 니들 패치는 치료를 위한 약물 전달 외에도 백신 전달을 통한 질병 예방과 피부 미용을 위한 약물 전달 등에 활용될 수 있다.The microneedle or the microneedle patch of the present invention can be used for drug delivery for skin prevention and disease prevention through vaccine delivery in addition to drug delivery for treatment.

Claims (13)

  1. 화학식 1로 표시되며, 피하 또는 상피에 삽입된 후 흡수 및 분해되어 마그네슘 또는 아연 금속 이온과 분해산물을 체내에 방출하는 것을 특징으로 하는 생체분해성 금속을 이용한 마이크로 니들:A microneedle using a biodegradable metal, which is represented by Formula 1 and inserted into the subcutaneous or epithelium and is absorbed and decomposed to release magnesium or zinc metal ions and decomposition products in the body:
    [화학식 1][Formula 1]
    MgaZnbXc Mg a Zn b X c
    화학식 1에서 a, b 및 c는 각 성분의 중량%로서, a+b+c=100중량%이고, 0≤a≤100, 0≤b≤100, 0≤c≤10 범위중 a 또는 b가 가장 크며, X는 Ca, Fe, Mn, Si, Na, Zr, Ce 및 P로 구성된 군에서 선택되는 1종 이상임.In Formula 1, a, b, and c are weight percents of each component, and a + b + c = 100 wt%, where a or b is in a range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, and 0 ≦ c ≦ 10. X is the one or more selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P.
  2. 제1항에 있어서, 상기 화학식 1의 a, b 및 c는 각 성분의 중량%로서, a+b+c=100중량%이고, i) 90≤a≤100, 0≤b≤10, 0≤c≤10 또는 ii) 0≤a≤10, 90≤b≤100, 0≤c≤10이며, X는 Ca, Fe, Mn, Si, Na, Zr, Ce 및 P로 구성된 군에서 선택되는 1종 이상인 것을 특징으로 하는 생체분해성 금속을 이용한 마이크로 니들.The method of claim 1, wherein a, b and c in the formula (1) is a weight percent of each component, a + b + c = 100% by weight, i) 90≤a≤100, 0≤b≤10, 0≤ c ≦ 10 or ii) 0 ≦ a ≦ 10, 90 ≦ b ≦ 100, 0 ≦ c ≦ 10, and X is one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce, and P Microneedle using a biodegradable metal, characterized in that above.
  3. 제1항에 있어서, 상기 생체분해성 금속은 불가피한 불순물을 포함한 순수 Mg인 것을 특징으로 하는 생체분해성 마이크로 니들.The biodegradable microneedle of claim 1, wherein the biodegradable metal is pure Mg including inevitable impurities.
  4. 제1항에 있어서, 상기 생체분해성 금속은 불가피한 불순물을 포함한 순수 Zn인 것을 특징으로 하는 마이크로 니들. The microneedle of claim 1, wherein the biodegradable metal is pure Zn including inevitable impurities.
  5. 제1항에 있어서, 상기 생체분해성 금속은 2 이상의 금속 상(phase)이 갈바닉 회로를 생성하여 분해속도가 가속화되는 것을 특징으로 하는 마이크로 니들.The microneedle of claim 1, wherein the biodegradable metal has two or more metal phases to generate a galvanic circuit, thereby accelerating the decomposition rate.
  6. 제5항에 있어서, 상기 마이크로 니들은 Mg2Ca 상을 포함하는 것을 특징으로 하는 마이크로 니들.6. The microneedle of claim 5, wherein the microneedle comprises an Mg 2 Ca phase.
  7. 제5항에 있어서, 상기 마이크로 니들은 MgZn 상을 포함하는 것을 특징으로 하는 마이크로 니들.6. The microneedle of claim 5 wherein the microneedle comprises an MgZn phase.
  8. 제5항에 있어서, 상기 마이크로 니들은 Ca2Mg6Zn3 상을 포함하는 것을 특징으로 하는 마이크로 니들.6. The microneedle of claim 5, wherein the microneedle comprises a Ca 2 Mg 6 Zn 3 phase.
  9. 제1항에 있어서, 상기 마이크로 니들은 갈바닉 회로를 형성시키기 위하여 금속 표면에 다른 종류의 제2의 금속이 코팅된 것을 특징으로 하는 마이크로 니들.2. The microneedle of claim 1, wherein the microneedle is coated with a second kind of metal on a metal surface to form a galvanic circuit.
  10. 제9항에 있어서, 상기 제2의 금속은 나트륨, 마그네슘, 칼륨, 철, 니켈, 아연, 갈륨, 셀레늄, 스트론튬, 지르코늄, 몰리브덴, 니오븀, 탄탈륨, 타이타늄, 규소, 은, 금, 망간 및 칼슘으로 구성된 군에서 선택되는 1종 이상의 금속인 것을 특징으로 하는 마이크로 니들.10. The method of claim 9, wherein the second metal is sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver, gold, manganese and calcium. Microneedle, characterized in that at least one metal selected from the group consisting of.
  11. 제1항에 있어서, 상기 마이크로 니들은 약물이 코팅되거나 담지되어 있는 것을 특징으로 하는 마이크로 니들.The microneedle of claim 1, wherein the microneedle is coated or supported with a drug.
  12. 제1항에 있어서, 상기 마이크로 니들은 박판 형인 것을 특징으로 하는 마이크로 니들.The microneedle of claim 1, wherein the microneedle is thin.
  13. 제1항의 마이크로 니들을 포함하는 것을 특징으로 하는 마이크로 니들 패치.A microneedle patch comprising the microneedle of claim 1.
PCT/KR2017/003792 2016-04-07 2017-04-07 Microneedle using biodegradable metal WO2017176077A1 (en)

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US16/091,718 US11135415B2 (en) 2016-04-07 2017-04-07 Microneedle using biodegradable metal
EP17779377.5A EP3444003B1 (en) 2016-04-07 2017-04-07 Microneedle using biodegradable metal
PL17779377.5T PL3444003T3 (en) 2016-04-07 2017-04-07 Microneedle using biodegradable metal
CN201780021995.1A CN109069814A (en) 2016-04-07 2017-04-07 Utilize the micropin of biodegradable metal
BR112018070666A BR112018070666A2 (en) 2016-04-07 2017-04-07 micro-needle using biodegradable metal
JP2019503883A JP6794528B2 (en) 2016-04-07 2017-04-07 Microneedle using biodegradable metal
MX2018012236A MX2018012236A (en) 2016-04-07 2017-04-07 Microneedle using biodegradable metal.

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