WO2012124869A1 - Drug delivery system including laminated structure - Google Patents

Drug delivery system including laminated structure Download PDF

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Publication number
WO2012124869A1
WO2012124869A1 PCT/KR2011/006945 KR2011006945W WO2012124869A1 WO 2012124869 A1 WO2012124869 A1 WO 2012124869A1 KR 2011006945 W KR2011006945 W KR 2011006945W WO 2012124869 A1 WO2012124869 A1 WO 2012124869A1
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Prior art keywords
delivery system
polymer
drug delivery
drug
layer
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PCT/KR2011/006945
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French (fr)
Korean (ko)
Inventor
조동일
홍석준
이상민
안재현
유형정
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서울대학교산학협력단
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Priority claimed from KR1020110045827A external-priority patent/KR101314127B1/en
Priority claimed from KR1020110045828A external-priority patent/KR101345442B1/en
Priority claimed from KR1020110045826A external-priority patent/KR101314126B1/en
Application filed by 서울대학교산학협력단 filed Critical 서울대학교산학협력단
Priority to US14/004,670 priority Critical patent/US9351924B2/en
Priority to US14/004,670 priority patent/US20140005600A1/en
Publication of WO2012124869A1 publication Critical patent/WO2012124869A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to a drug delivery system comprising a laminated structure.
  • the drug In order for the drug to function effectively in vivo, it must be able to be expressed at the intended target and the body's concentration of the drug at the target site must be maintained within the therapeutic range for a period of time. If the drug is present in the body in excess, it is toxic and if it is in too small a therapeutic effect, the drug delivery system may play a role in controlling it.
  • the present invention is to provide a drug delivery system that can release the drug sequentially to maintain a high drug concentration of the target site, and can easily control the rate or amount of drug release.
  • One aspect of the present invention provides a drug delivery system including a layer structure in which a drug layer and a biodegradable polymer layer for controlling drug release are alternately stacked.
  • the drug delivery system according to the present invention includes a layer structure in which the drug layer and the biodegradable polymer layer for controlling drug release are alternately stacked, so that the drug may be sequentially released, thereby maintaining the drug concentration at the target site at an appropriate level. Drug release rates or release rates can be readily controlled.
  • 1 is an example of a drug delivery system that includes a layered structure according to one aspect of the present invention.
  • drug delivery system refers to a formulation of a drug designed to control the rate of drug release or to deliver the drug efficiently to a target site.
  • polymer means a compound having a molecular weight of 10,000 or more
  • biodegradability means a property that can be degraded in vivo.
  • Drug delivery systems made of biodegradable polymers are highly clinically useful in that they can be administered by selecting a specific site and are simple to administer and do not require separate surgical procedures, such as pharmacy, polymer chemistry, and biotechnology. It is one of the advanced technologies that are widely studied in various fields.
  • the drug delivery system made of conventional biodegradable polymers is made entirely of one biodegradable polymer, and its shape is simple. Therefore, it is not easy to have a special function other than the simple drug release due to biodegradation, and it is difficult to maintain practically high drug concentration around the target site, and thus could not be widely applied in the clinical medicine field.
  • One aspect of the present invention provides a drug delivery system including a layer structure in which a drug layer and a biodegradable polymer layer for controlling drug release are alternately stacked.
  • the biodegradable polymer layer for controlling drug release must be decomposed to release the drug in the drug layer underneath, so that the thickness and width of the biodegradable polymer layer for controlling drug release or the kind of polymer The drug release rate or release amount of the drug can be adjusted according to the method.
  • the drug delivery system enables precise control of the drug release rate or release amount than the conventional drug delivery system, thereby adjusting the release concentration of the drug or the release amount at the site to adjust the concentration of the drug at the target site. Can be kept high.
  • each drug layer includes a different drug, it may be possible to release the other drug in the drug delivery system over time after entering the body. This will be particularly useful when the drug delivery system needs to release a different drug at each site in its pathway as it moves in vivo.
  • the layer structure of the drug delivery system may vary depending on the number of drugs to be released or the site to which the drugs are to be released.
  • the layer structure may comprise 2 to 10 layers, specifically 4 to 8 layers.
  • the number of laminated drug layers and biodegradable polymer layers for controlling drug release may be the same or different.
  • biodegradable polymer layers for controlling drug release of a drug delivery system
  • polymers of each polymer layer may have different biodegradation rates.
  • Biodegradable polymer layer of the drug delivery system may be 2 to 5, specifically 2 to 4.
  • the biodegradable polymer is poly-caprolactone (PCL), L-poly-lactide (L-poly-lactides, LPLA), poly-glycolic acid, PGA), poly-D-lactide (PDLA), poly-lactic acid (PLA), poly-lactic-co-glycolic acid (PLGA) ), Polyvinylacetate phthalate, one or more selected from the group consisting of methacrylic acid polymers and hydroxypropyl methylcellulose phthalate, but is not limited thereto.
  • the drug layer of the drug delivery system may be a layer consisting of drugs only.
  • the drug layer may be a drug layer comprising a biodegradable polymer, that is, a layer prepared based on the biodegradable polymer and containing a drug.
  • the drug delivery system may further include a biodegradable polymer outer layer surrounding the layer structure.
  • a biodegradable polymer outer layer surrounding the layer structure.
  • Such a drug delivery system can control the release rate, release rate or release amount of the drug by controlling the biodegradation rate of the outer layer polymer.
  • the polymer outer layer may have a thickness of 10 ⁇ m to 30 ⁇ m, specifically 15 ⁇ m to 20 ⁇ m. In the case of having the thickness in the above range, not only is the present invention suitable for exhibiting the intended effect, but also satisfies both the stability and safety of the drug delivery system, and may be appropriate in terms of cost-effectiveness.
  • the polymer outer layer may include an opening, wherein in order to set the drug release order of the drug layer, specifically to allow the drug of the drug layer close to the opening to be released first,
  • the polymer may be a polymer having a lower biodegradation rate than the polymer of the polymer layer in the layer structure.
  • the drug delivery system further comprises a polymer cover covering the opening, the biodegradation rate of the polymer may be low in the order of the polymer of the outer layer, the polymer of the polymer layer of the layer structure and the polymer of the cover.
  • the cover serves to determine the time point of drug release of the drug delivery system, and the time point may be determined by adjusting the thickness and width of the cover or the type of cover polymer.
  • the polymer of the outer layer comprises poly-caprolactone (PCL) or L-poly-lactide (L-poly-lactides, LPLA), biodegradation for controlling drug release in the layer structure
  • PCL poly-caprolactone
  • L-poly-lactide L-poly-lactides
  • LPLA L-poly-lactides
  • the polymer of the polymer layer includes poly-glycolic acid (PGA) or poly-D-lactide (PDLA), and the polymer on the cover is poly-lactic acid. , PLA) or poly-lactic-co-glycolic acid (PLGA).
  • the outer layer may have a thickness of 10 ⁇ m to 30 ⁇ m, specifically 15 ⁇ m to 20 ⁇ m
  • the biodegradable polymer layer for controlling drug release in the layer structure is 400 ⁇ m 2 to 10,000 ⁇ m 2 It can have an area of 4,000 ⁇ m 2 to 6,000 ⁇ m 2
  • the lid can have an area of 5,000 ⁇ m 2 to 12,000 ⁇ m 2 , specifically an area of 6,000 ⁇ m 2 to 8,000 ⁇ m 2 .
  • the present invention is not only suitable for achieving the intended effect, but also satisfies both the stability and safety of the drug delivery system, and may be appropriate in terms of cost-effectiveness.
  • the drug delivery system of the drug delivery system may be two or more, and each drug layer may include the same or different drugs.
  • the drug includes all substances applicable to animals or plants, including humans, for treating or preventing diseases or wounds, and biochemicals such as general therapeutic drugs, enzymes or miRNAs. It is a concept that is also widely included.
  • the drug may be liquid or solid.
  • the drug is a nonsteroidal anti-inflammatory analgesic agent, calcium channel blocker, angiotensin II antagonist, hyperlipidemia treatment, diabetes treatment, lipase inhibitor, antihistamine, digestive system disease treatment, platelet aggregation inhibitor, osteoporosis treatment, anti Viral agents, antibiotics, antifungal agents, immunosuppressive agents, hormonal agents, antitumor agents, salts thereof, and pharmaceutical derivatives thereof.
  • the drug comprises a nonsteroidal anti-inflammatory analgesic including acetaminophen, acetylsalicylic acid, ibuprofen, flubiprofen, indomethacin, naproxen, ketoprofen, pyoxycampin or aceclofenac; Calcium channel blockers including nifedipine or nimodipine; Angiotensin II antagonists, including valsartan, irbesartan, candersartan, olmesartanjan or losartan; Agents for treating hyperlipidemia, including atorvastatin, lovastatin, simvastatin, fluvastatin, gemfibrozil or fenofibrate; Antidiabetic agents, including rosiglitazone or metformin; Lipase inhibitors including orlistat; Antihistamines, including phenylamine or fexofenadine; Therapeutic agents for the digestive system, including omeprazol
  • the drug delivery system according to one aspect of the present invention may have the shape of a sphere.
  • the drug delivery system according to another aspect of the present invention may have a polyhedron shape, and the polyhedron may include 3 to 10 polyhedrons, specifically 4 to 8 polyhedrons, more specifically 4 to 6 polyhedrons, but are not limited thereto. no.
  • Conventional drug delivery systems are mostly spherical in shape to maintain linear drug release by biodegradation. In the case of surface treatment to impart various functions to such spherical biodegradable polymer drug delivery system, it is difficult to divide the surface into several areas and to surface only a specific area because of the characteristics of the sphere. It was difficult to give functionality.
  • the drug delivery system according to one aspect of the present invention has a polyhedral shape, thereby more precisely dividing the surface of the micro-sized drug delivery system into several areas, which is impossible in the conventional drug delivery system, and applying the surface treatment to only a part of the targeted area It is possible to do
  • the polyhedron is a rectangular parallelepiped, it is particularly easy to divide the outer surface into several regions and to surface-treat only a portion of the regions.
  • the drug delivery system according to one aspect of the invention may include one or more exterior surfaces that have been surface treated to impart function to the drug delivery system.
  • the drug delivery system according to another aspect of the present invention may include two or more outer surfaces that have been surface treated, and each outer surface that has been surface treated may have a different surface treatment.
  • the surface treatment may be performed only on a portion of the surface even in the surface treatment.
  • the surface treatment comprises one or more of physical etching, chemical etching, chemical coating and microbial adsorption.
  • the chemicals include bovine serum albumin (BSA).
  • BSA bovine serum albumin
  • the drug delivery system according to the present invention can maximize the effect in the surface treatment having a straightness, such as plasma treatment or chemical vapor deposition.
  • the microorganism includes a microorganism having mobility using flagella and the like, specifically, having mobility to the source of stimulation in response to external stimuli, that is, taxis. More specifically, the microorganism includes a microorganism having a main character for cancer cells. If the drug delivery system has a surface treatment in which such microorganisms are adsorbed, the adsorbed microorganisms move in response to a disease such as a specific environment or cancer, thereby causing the drug delivery system to move to a target site. do.
  • the microorganism may be a microorganism capable of increasing its own population so that the microorganism can give sufficient mobility to the drug delivery system until the drug delivery system reaches the target site.
  • the drug delivery system in the case of adsorbing microorganisms on the outer surface of the drug delivery system including a polymer outer layer having a low biodegradation rate, the drug delivery system is mobile by the microorganisms adsorbed on the outer surface while the drug is released through the opening. Can still hold.
  • the microorganism may include bacteria, specifically Escherichia Coli , Serratia Marcescens or Salmonella Typhimurium , but is not limited thereto. It is not.
  • One aspect of the present invention provides a method for manufacturing a drug delivery system comprising alternately stacking a drug layer and a biodegradable polymer layer for controlling drug release.
  • the step of alternately stacking the drug layer and the biodegradable polymer layer for controlling drug release may include injecting the drug and the polymer alternately.
  • Another aspect of the invention comprises the steps of preparing a polymer outer layer; And it provides a drug delivery system manufacturing method comprising a polymer outer layer comprising the step of alternately laminating the drug layer and the biodegradable polymer layer for controlling drug release.
  • Another aspect of the present invention comprises the steps of preparing a polymer outer layer; Alternately laminating the drug layer and the biodegradable polymer layer for controlling drug release; And it provides a drug delivery system manufacturing method comprising a polymer cover comprising forming a polymer cover covering the opening.
  • the forming of the polymer cover may include injecting the polymer into the opening of the outer layer by a micro syringe.

Abstract

One aspect of the present invention relates to a drug delivery system comprising a layered structure where a drug layer and a biodegradable polymer layer for controlling the release of drugs are alternately laminated. The drug delivery system can easily control an in-vivo drug release rate and a release amount.

Description

적층 구조를 포함하는 약물 전달 시스템Drug Delivery System Including Laminated Structures
본 발명은 적층 구조를 포함하는 약물 전달 시스템에 관한 것이다.The present invention relates to a drug delivery system comprising a laminated structure.
약물이 생체 내에서 효과적으로 작용하기 위해서는 의도하는 타겟에서 발현될 수 있어야 하며, 타겟 부위에서 약물의 체내 농도가 일정 기간 이상 치료 효과 범위(therapeutic range) 내에 유지되어야 한다. 약물이 체내에 과량으로 존재하면 독성을 나타내고 너무 적은 양으로 존재하면 치료 효과가 나타나지 않는데, 약물 전달 시스템은 이를 조절하는 역할을 할 수 있다.In order for the drug to function effectively in vivo, it must be able to be expressed at the intended target and the body's concentration of the drug at the target site must be maintained within the therapeutic range for a period of time. If the drug is present in the body in excess, it is toxic and if it is in too small a therapeutic effect, the drug delivery system may play a role in controlling it.
본 발명은 순차적으로 약물이 방출되어 타겟 부위의 약물 농도를 높게 유지시킬 수 있고, 약물 방출 속도 또는 방출량을 용이하게 조절할 수 있는 약물 전달 시스템을 제공하고자 한다.The present invention is to provide a drug delivery system that can release the drug sequentially to maintain a high drug concentration of the target site, and can easily control the rate or amount of drug release.
본 발명의 일측면은 약물층과 약물 방출 조절용 생분해성 고분자층이 번갈아 적층되어 있는 층 구조를 포함하는 약물 전달 시스템을 제공한다.One aspect of the present invention provides a drug delivery system including a layer structure in which a drug layer and a biodegradable polymer layer for controlling drug release are alternately stacked.
본 발명에 따른 약물 전달 시스템은 약물층과 약물 방출 조절용 생분해성 고분자층이 번갈아 적층되어 있는 층 구조를 포함함으로써, 순차적으로 약물을 방출할 수 있으므로 타겟 부위의 약물 농도를 적정선에서 유지시킬 수 있으며, 약물 방출 속도 또는 방출량을 용이하게 조절할 수 있다.The drug delivery system according to the present invention includes a layer structure in which the drug layer and the biodegradable polymer layer for controlling drug release are alternately stacked, so that the drug may be sequentially released, thereby maintaining the drug concentration at the target site at an appropriate level. Drug release rates or release rates can be readily controlled.
도 1은 본 발명의 일측면에 따른 층 구조를 포함하는 약물 전달 시스템의 일예시이다.1 is an example of a drug delivery system that includes a layered structure according to one aspect of the present invention.
본 명세서에서 “약물 전달 시스템”은 약물 방출 속도를 조절하거나 약물을 타겟 부위에 효율적으로 전달하기 위해 설계한 약물의 제형을 의미한다.As used herein, "drug delivery system" refers to a formulation of a drug designed to control the rate of drug release or to deliver the drug efficiently to a target site.
본 명세서에서 “고분자”는 분자량 1만 이상의 화합물을 의미하며, “생분해성”은 생체 내에서 분해 가능한 성질을 의미한다.As used herein, "polymer" means a compound having a molecular weight of 10,000 or more, and "biodegradability" means a property that can be degraded in vivo.
생분해성 고분자로 제작된 약물 전달 시스템은 특정 부위를 선택하여 약물을 투여할 수 있으며 그 투입이 간단하고 별도의 제거 수술이 필요 없다는 점에서 임상 의학적으로 유용성이 높아, 약학, 고분자 화학, 생명 공학 등 다양한 분야에서 널리 연구되고 있는 첨단 기술 중 하나이다.Drug delivery systems made of biodegradable polymers are highly clinically useful in that they can be administered by selecting a specific site and are simple to administer and do not require separate surgical procedures, such as pharmacy, polymer chemistry, and biotechnology. It is one of the advanced technologies that are widely studied in various fields.
기존의 생분해성 고분자로 제작된 약물 전달 시스템은 전체가 1종의 생분해성 고분자로 제작되고, 그 형상이 단순하다. 따라서 생분해에 따른 단순한 약물 방출 외에 특별한 기능을 가지기 쉽지 않으며, 타겟 부위 주변에서 특히 높은 약물 농도를 유지시키는 것이 어렵기 때문에 임상 의학 분야에서 실질적으로 널리 응용될 수는 없었다.The drug delivery system made of conventional biodegradable polymers is made entirely of one biodegradable polymer, and its shape is simple. Therefore, it is not easy to have a special function other than the simple drug release due to biodegradation, and it is difficult to maintain practically high drug concentration around the target site, and thus could not be widely applied in the clinical medicine field.
이하, 본 발명을 상세하게 설명한다.EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.
본 발명의 일측면은 약물층과 약물 방출 조절용 생분해성 고분자층이 번갈아 적층되어 있는 층 구조를 포함하는 약물 전달 시스템을 제공한다. 이와 같은 약물 전달 시스템을 생체 내에 투여하는 경우 약물 방출 조절용 생분해성 고분자층이 분해되어야 그 아래에 있는 약물층의 약물이 방출될 수 있으므로, 약물 방출 조절용 생분해성 고분자층의 두께 및 넓이 또는 고분자의 종류에 따라 약물의 약물 방출 속도 또는 방출량을 조절할 수 있다. 이와 같이 본 발명의 일측면에 따른 약물 전달 시스템은 기존의 약물 전달 시스템보다 약물 방출 속도 또는 방출량의 정밀한 조절이 가능하므로 약물의 방출 부위 또는 그 부위에서의 방출량을 조절하여 타겟하는 부위의 약물 농도를 높게 유지시킬 수 있다. 또한 각 약물층들이 각각 다른 약물을 포함하도록 하는 경우, 체내 투입 후 시간의 흐름에 따라 약물 전달 시스템에서 다른 약물이 방출되도록 할 수도 있다. 이는 약물 전달 시스템이 생체 내에서 이동할 때 그 경로에 있는 각 부위에서 각각 다른 약물이 방출될 필요가 있을 때 특히 유용할 것이다.One aspect of the present invention provides a drug delivery system including a layer structure in which a drug layer and a biodegradable polymer layer for controlling drug release are alternately stacked. In the case of administering such a drug delivery system in vivo, the biodegradable polymer layer for controlling drug release must be decomposed to release the drug in the drug layer underneath, so that the thickness and width of the biodegradable polymer layer for controlling drug release or the kind of polymer The drug release rate or release amount of the drug can be adjusted according to the method. As described above, the drug delivery system according to an aspect of the present invention enables precise control of the drug release rate or release amount than the conventional drug delivery system, thereby adjusting the release concentration of the drug or the release amount at the site to adjust the concentration of the drug at the target site. Can be kept high. In addition, when each drug layer includes a different drug, it may be possible to release the other drug in the drug delivery system over time after entering the body. This will be particularly useful when the drug delivery system needs to release a different drug at each site in its pathway as it moves in vivo.
본 발명의 일측면에 따른 약물 전달 시스템의 층 구조는 방출하고자 하는 약물의 개수 또는 약물을 방출하고자 하는 부위에 따라 달라질 수 있다. 본 발명의 다른 일측면에서, 층 구조는 2 내지 10개의 층, 구체적으로 4 내지 8개의 층을 포함할 수 있다. 이 때 적층된 약물층과 약물 방출 조절용 생분해성 고분자층의 개수는 동일하거나 상이할 수 있다.The layer structure of the drug delivery system according to one aspect of the present invention may vary depending on the number of drugs to be released or the site to which the drugs are to be released. In another aspect of the invention, the layer structure may comprise 2 to 10 layers, specifically 4 to 8 layers. In this case, the number of laminated drug layers and biodegradable polymer layers for controlling drug release may be the same or different.
본 발명의 일측면에 따른 약물 전달 시스템의 약물 방출 조절용 생분해성 고분자층은 복수 개이고, 각 고분자층의 고분자는 서로 다른 생분해 속도를 가질 수 있다. 이와 같이 서로 다른 생분해 속도를 가지는 각 고분자층의 고분자를 이용하여 각 고분자층과 번갈아 적층된 각 약물층의 약물 방출 속도 또는 방출량을 용이하고 정밀하게 조절할 수 있다. 본 발명의 다른 일측면에 따른 약물 전달 시스템의 생분해성 고분자층은 2개 내지 5개, 구체적으로 2개 내지 4개일 수 있다. 본 발명의 다른 일측면에서, 생분해성 고분자는 폴리-카프로락톤(poly-caprolactone, PCL), L-폴리-락타이드(L-poly-lactides, LPLA), 폴리-글리콜산(poly-glycolic acid, PGA), 폴리-D-락타이드(poly-D-lactide, PDLA), 폴리-락트산(poly-lactic acid, PLA), 폴리-락틱-코-글리콜산(poly-lactic-co-glycolic acid, PLGA), 폴리비닐아세테이트 프탈레이트(polyvinylacetate phthalate), 메타크릴산 공중합체(methacrylic acid polymer) 및 하이드록시프로필 메틸셀룰로오즈 프탈레이트(hydroxypropyl methylcellulose phthalate)로 이루어진 군에서 선택된 하나 이상을 포함하나, 이에 제한되는 것은 아니다.According to an aspect of the present invention, there are a plurality of biodegradable polymer layers for controlling drug release of a drug delivery system, and polymers of each polymer layer may have different biodegradation rates. Thus, by using the polymer of each polymer layer having a different biodegradation rate, the drug release rate or release amount of each drug layer alternately stacked with each polymer layer can be easily and precisely controlled. Biodegradable polymer layer of the drug delivery system according to another aspect of the present invention may be 2 to 5, specifically 2 to 4. In another aspect of the invention, the biodegradable polymer is poly-caprolactone (PCL), L-poly-lactide (L-poly-lactides, LPLA), poly-glycolic acid, PGA), poly-D-lactide (PDLA), poly-lactic acid (PLA), poly-lactic-co-glycolic acid (PLGA) ), Polyvinylacetate phthalate, one or more selected from the group consisting of methacrylic acid polymers and hydroxypropyl methylcellulose phthalate, but is not limited thereto.
본 발명의 일측면에 따른 약물 전달 시스템의 약물층은 약물만으로 이루어진 층일 수 있다. 본 발명의 다른 일측면에서, 약물층은 생분해성 고분자를 포함하는 약물층, 즉 생분해성 고분자를 기반으로 제조되고, 약물을 포함하는 층일 수 있다.The drug layer of the drug delivery system according to one aspect of the present invention may be a layer consisting of drugs only. In another aspect of the present invention, the drug layer may be a drug layer comprising a biodegradable polymer, that is, a layer prepared based on the biodegradable polymer and containing a drug.
본 발명의 일측면에 따른 약물 전달 시스템은 층 구조를 감싸는 생분해성 고분자 외층을 더 포함할 수 있다. 이와 같은 약물 전달 시스템은 외층 고분자의 생분해 속도를 조절함으로써, 약물 방출 시점, 방출 속도 또는 방출량을 조절할 수 있다. 본 발명의 다른 일측면에서, 고분자 외층은 10 ㎛ 내지 30 ㎛, 구체적으로 15 ㎛ 내지 20 ㎛의 두께를 가질 수 있다. 상기 범위의 두께를 가지는 경우 본 발명이 의도한 효과를 나타내기에 적절할 뿐만 아니라, 약물 전달 시스템의 안정성 및 안전성을 모두 만족할 수 있으며, 비용 대비 효과의 측면에서도 적절할 수 있다.The drug delivery system according to one aspect of the present invention may further include a biodegradable polymer outer layer surrounding the layer structure. Such a drug delivery system can control the release rate, release rate or release amount of the drug by controlling the biodegradation rate of the outer layer polymer. In another aspect of the invention, the polymer outer layer may have a thickness of 10 ㎛ to 30 ㎛, specifically 15 ㎛ to 20 ㎛. In the case of having the thickness in the above range, not only is the present invention suitable for exhibiting the intended effect, but also satisfies both the stability and safety of the drug delivery system, and may be appropriate in terms of cost-effectiveness.
본 발명의 일측면에서, 고분자 외층은 개구부를 포함할 수 있고, 이 때 약물층의 약물 방출 순서를 설정하기 위해, 구체적으로는 개구부에 가까운 약물층의 약물이 먼저 방출되도록 하기 위해, 고분자 외층의 고분자는 층 구조 중 고분자층의 고분자보다 생분해 속도가 낮은 고분자일 수 있다.In one aspect of the invention, the polymer outer layer may include an opening, wherein in order to set the drug release order of the drug layer, specifically to allow the drug of the drug layer close to the opening to be released first, The polymer may be a polymer having a lower biodegradation rate than the polymer of the polymer layer in the layer structure.
본 발명의 일측면에서, 약물 전달 시스템은 개구부를 덮는 고분자 덮개를 더 포함하고, 상기에서 외층의 고분자, 층 구조 중 고분자층의 고분자 및 덮개의 고분자 순으로 고분자의 생분해 속도가 낮을 수 있다. 상기 덮개는 약물 전달 시스템의 약물 방출 시점을 결정하는 역할을 하며, 덮개의 두께 및 넓이 또는 덮개 고분자의 종류를 조절함으로써 상기 시점을 결정할 수 있다. 본 발명의 다른 일측면에서, 외층의 고분자는 폴리-카프로락톤(poly-caprolactone, PCL) 또는 L-폴리-락타이드(L-poly-lactides, LPLA)를 포함하고, 층 구조 중 약물 방출 조절용 생분해성 고분자층의 고분자는 폴리-글리콜산(poly-glycolic acid, PGA) 또는 폴리-D-락타이드(poly-D-lactide, PDLA)를 포함하며, 덮개의 고분자는 폴리-락트산(poly-lactic acid, PLA) 또는 폴리-락틱-코-글리콜산(poly-lactic-co-glycolic acid, PLGA)을 포함할 수 있다.In one aspect of the invention, the drug delivery system further comprises a polymer cover covering the opening, the biodegradation rate of the polymer may be low in the order of the polymer of the outer layer, the polymer of the polymer layer of the layer structure and the polymer of the cover. The cover serves to determine the time point of drug release of the drug delivery system, and the time point may be determined by adjusting the thickness and width of the cover or the type of cover polymer. In another aspect of the invention, the polymer of the outer layer comprises poly-caprolactone (PCL) or L-poly-lactide (L-poly-lactides, LPLA), biodegradation for controlling drug release in the layer structure The polymer of the polymer layer includes poly-glycolic acid (PGA) or poly-D-lactide (PDLA), and the polymer on the cover is poly-lactic acid. , PLA) or poly-lactic-co-glycolic acid (PLGA).
본 발명의 일측면에서, 외층, 층 구조 중 약물 방출 조절용 생분해성 고분자층 또는 덮개의 넓이 및 두께를 조절함으로써, 약물의 방출 부위 또는 방출 속도를 조절할 수 있다. 본 발명의 다른 일측면에서, 외층은 10 μm 내지 30 μm의 두께, 구체적으로 15 μm 내지 20 μm의 두께를 가질 수 있으며, 층 구조 중 약물 방출 조절용 생분해성 고분자층은 400 μm2 내지 10,000 μm2의 넓이, 구체적으로 4,000 μm2 내지 6,000 μm2의 넓이를 가질 수 있고, 덮개는 5,000 μm2 내지 12,000 μm2의 넓이, 구체적으로 6,000 μm2 내지 8,000 μm2의 넓이를 가질 수 있다. 상기 범위의 두께 또는 넓이를 가지는 경우 본 발명이 의도한 효과를 나타내기에 적절할 뿐만 아니라, 약물 전달 시스템의 안정성 및 안전성을 모두 만족할 수 있으며, 비용 대비 효과의 측면에서도 적절할 수 있다.In one aspect of the present invention, by controlling the width and thickness of the outer layer, biodegradable polymer layer or cover for controlling drug release in the layer structure, it is possible to control the release site or release rate of the drug. In another aspect of the invention, the outer layer may have a thickness of 10 μm to 30 μm, specifically 15 μm to 20 μm, and the biodegradable polymer layer for controlling drug release in the layer structure is 400 μm 2 to 10,000 μm 2 It can have an area of 4,000 μm 2 to 6,000 μm 2 , and the lid can have an area of 5,000 μm 2 to 12,000 μm 2 , specifically an area of 6,000 μm 2 to 8,000 μm 2 . In the case of having a thickness or a width in the above range, the present invention is not only suitable for achieving the intended effect, but also satisfies both the stability and safety of the drug delivery system, and may be appropriate in terms of cost-effectiveness.
도 1(100: 약물 전달 시스템 외층, 110: 약물층, 111: 약물 방출 조절용 생분해성 고분자층, 120: 약물 전달 시스템 덮개)은 본 발명의 일측면에 따른 약물 전달 시스템의 일예시이나, 이는 일예시일 뿐 본 발명의 범위가 이에 의해 제한되는 것은 아니다.1 (100: drug delivery system outer layer, 110: drug layer, 111: biodegradable polymer layer for drug release control, 120: drug delivery system cover) is an example of a drug delivery system according to an aspect of the present invention, The scope of the present invention is by way of example only and is not limited thereto.
본 발명의 일측면에 따른 약물 전달 시스템의 약물층은 두 개 이상일 수 있고, 각 약물층은 동일하거나 상이한 약물을 포함할 수 있다. 본 발명의 다른 일측면에서, 약물은 질병이나 상처를 치료하거나 예방하기 위해 인간을 포함하는 동물 또는 식물에 적용할 수 있는 모든 물질을 포함하며, 일반적인 치료용 약물, 효소 또는 miRNA와 같은 생화학적 물질도 널리 포함하는 개념이다. 본 발명의 또 다른 일측면에서, 약물은 액상 또는 고상일 수 있다. 본 발명의 또 다른 일측면에서, 약물은 비스테로이드성 소염 진통제, 칼슘 통로 차단제, 안지오텐신 II 길항제, 고지혈증 치료제, 당뇨병 치료제, 리파아제 억제제, 항히스타민제, 소화기계 질환 치료제, 혈소판 응집 억제제, 골다공증 치료제, 항바이러스제, 항생제, 항진균제, 면역 억제제, 호르몬제, 항종양제, 이들의 염 및 이들의 약제학적 유도체 중 선택된 하나 이상을 포함할 수 있다. 본 발명의 또 다른 일측면에서, 약물은 아세트아미노펜, 아세틸살리실산, 이부프로펜, 플루비프로펜, 인도메타신, 나프록센, 케토프로펜, 피록시캄　또는 아세클로페낙을 포함하는 비스테로이드성 소염 진통제; 니페디핀 또는 니모디핀을 포함하는 칼슘 통로 차단제; 발사르탄, 이르베사르탄, 칸데르사르탄, 올메사르탄　또는 로사르탄을 포함하는 안지오텐신 II 길항제; 아토르바스타틴, 로바스타틴, 심바스타틴, 플루바스타틴, 겜피브로질 또는 페노피브레이트를 포함하는 고지혈증 치료제; 로지글리타존　또는 메트포민을 포함하는 당뇨병 치료제; 오를리스타트를 포함하는 리파아제 억제제; 페닐아민　또는 펙소페나딘을 포함하는 항히스타민제; 오메프라졸, 판토프라졸, 파모티딘 또는 시메티딘을 포함하는 소화기계 질환 치료제; 실로스타졸 또는 클로피도그렐을 포함하는 혈소판응집 억제제; 랄록시펜을 포함하는 골다공증 치료제; 아시클로버, 팜시클로버 또는 라미부딘을 포함하는 항바이러스제; 클라리스로마이신, 씨플로플록사신　또는 세푸록심을 포함하는 항생제; 이트라코나졸, 암포테리신 비, 테르비나핀, 플루코나졸　또는 케토코나졸을 포함하는 항진균제; 사이클로스포린, 타크로리무스 또는 라파마이신을 포함하는 면역 억제제; 테스토스테론, 프레드니솔론, 에스트로겐, 코티손, 하이드로코티손　또는 덱사메타손을 포함하는 호르몬제; 파클리탁셀, 도세탁셀, 독소루비신, 또는 부설판을 포함하는 항종양제; 이들의 염; 및 이들의 약제학적 유도체 중 선택된 하나 이상을 예로 들 수 있으나, 이에 제한되는 것은 아니다.The drug delivery system of the drug delivery system according to one aspect of the present invention may be two or more, and each drug layer may include the same or different drugs. In another aspect of the invention, the drug includes all substances applicable to animals or plants, including humans, for treating or preventing diseases or wounds, and biochemicals such as general therapeutic drugs, enzymes or miRNAs. It is a concept that is also widely included. In another aspect of the invention, the drug may be liquid or solid. In another aspect of the invention, the drug is a nonsteroidal anti-inflammatory analgesic agent, calcium channel blocker, angiotensin II antagonist, hyperlipidemia treatment, diabetes treatment, lipase inhibitor, antihistamine, digestive system disease treatment, platelet aggregation inhibitor, osteoporosis treatment, anti Viral agents, antibiotics, antifungal agents, immunosuppressive agents, hormonal agents, antitumor agents, salts thereof, and pharmaceutical derivatives thereof. In another aspect of the invention, the drug comprises a nonsteroidal anti-inflammatory analgesic including acetaminophen, acetylsalicylic acid, ibuprofen, flubiprofen, indomethacin, naproxen, ketoprofen, pyoxycampin or aceclofenac; Calcium channel blockers including nifedipine or nimodipine; Angiotensin II antagonists, including valsartan, irbesartan, candersartan, olmesartanjan or losartan; Agents for treating hyperlipidemia, including atorvastatin, lovastatin, simvastatin, fluvastatin, gemfibrozil or fenofibrate; Antidiabetic agents, including rosiglitazone or metformin; Lipase inhibitors including orlistat; Antihistamines, including phenylamine or fexofenadine; Therapeutic agents for the digestive system, including omeprazole, pantoprazole, pamotidine or cimetidine; Platelet aggregation inhibitors, including cilostazol or clopidogrel; Osteoporosis therapies including raloxifene; Antiviral agents including acyclovir, famcyclovir or lamivudine; Antibiotics including clarithromycin, ciflofloxacin or cefuroxime; Antifungal agents, including itraconazole, amphotericin ratio, terbinafine, fluconazole or ketoconazole; Immunosuppressive agents including cyclosporin, tacrolimus or rapamycin; Hormones including testosterone, prednisolone, estrogen, cortisone, hydrocortisone or dexamethasone; Anti-tumor agents including paclitaxel, docetaxel, doxorubicin, or busulfan; Salts thereof; And one or more selected from pharmaceutical derivatives thereof, but is not limited thereto.
본 발명의 일측면에 따른 약물 전달 시스템은 구(球)의 형상을 가질 수 있다. 본 발명의 다른 일측면에 따른 약물 전달 시스템은 다면체의 형상을 가질 수 있으며, 상기 다면체는 3 내지 10면체, 구체적으로 4 내지 8면체, 더 구체적으로 4 내지 6면체를 포함하나, 이에 제한되는 것은 아니다. 종래 약물 전달 시스템들은 생분해에 의한 약물 방출을 선형적으로 유지하고자 대부분 구(球)의 형상을 가진다. 이러한 구 형상의 생분해성 고분자 약물 전달 시스템에 다양한 기능을 부여하기 위해 표면 처리를 하는 경우, 구의 특성상 표면을 몇 개의 영역으로 나누고 특정 영역에만 표면 처리를 하는 것이 용이하지 않기 때문에 약물 전달 시스템들에 다양한 기능을 부여하기가 어려웠다. 본 발명의 일측면에 따른 약물 전달 시스템은 다면체 형상을 가짐으로써, 기존의 약물 전달 시스템에서는 불가능했던 마이크로 크기의 약물 전달 시스템의 표면을 여러 영역으로 보다 정밀하게 나누고, 타겟하는 일부 영역에만 표면 처리를 하는 것이 가능하다. 본 발명의 또 다른 일측면에서, 다면체가 직육면체일 경우 외면을 몇 개의 영역으로 나누고 일부 영역에만 표면 처리하는 것이 특히 용이하여 보다 바람직할 수 있다.The drug delivery system according to one aspect of the present invention may have the shape of a sphere. The drug delivery system according to another aspect of the present invention may have a polyhedron shape, and the polyhedron may include 3 to 10 polyhedrons, specifically 4 to 8 polyhedrons, more specifically 4 to 6 polyhedrons, but are not limited thereto. no. Conventional drug delivery systems are mostly spherical in shape to maintain linear drug release by biodegradation. In the case of surface treatment to impart various functions to such spherical biodegradable polymer drug delivery system, it is difficult to divide the surface into several areas and to surface only a specific area because of the characteristics of the sphere. It was difficult to give functionality. The drug delivery system according to one aspect of the present invention has a polyhedral shape, thereby more precisely dividing the surface of the micro-sized drug delivery system into several areas, which is impossible in the conventional drug delivery system, and applying the surface treatment to only a part of the targeted area It is possible to do In another aspect of the present invention, when the polyhedron is a rectangular parallelepiped, it is particularly easy to divide the outer surface into several regions and to surface-treat only a portion of the regions.
본 발명의 일측면에 따른 약물 전달 시스템은 약물 전달 시스템에 기능을 부여하기 위한 표면 처리가 된 하나 이상의 외면을 포함할 수 있다. 본 발명의 다른 일측면에 따른 약물 전달 시스템은 표면 처리가 된 두 개 이상의 외면을 포함할 수 있으며, 이 때 표면 처리가 된 각 외면은 서로 다른 표면 처리가 되어 있을 수 있다. 본 발명의 또 다른 일측면에서, 표면 처리가 된 면 내에서도 일부의 영역에만 표면 처리가 될 수 있다.The drug delivery system according to one aspect of the invention may include one or more exterior surfaces that have been surface treated to impart function to the drug delivery system. The drug delivery system according to another aspect of the present invention may include two or more outer surfaces that have been surface treated, and each outer surface that has been surface treated may have a different surface treatment. In still another aspect of the present invention, the surface treatment may be performed only on a portion of the surface even in the surface treatment.
본 발명의 일측면에서, 표면 처리는 물리적 식각(etching), 화학적 식각, 화학 물질 코팅 및 미생물 흡착 중 하나 이상을 포함한다. 상기에서 화학 물질은 소 혈청 알부민(bovine serum albumin, BSA)을 예로 들 수 있다. 본 발명에 따른 약물 전달 시스템은 플라즈마 처리 또는 화학 물질 증착과 같이 직진성을 가지는 표면 처리를 함에 있어 그 효과가 극대화될 수 있다. In one aspect of the invention, the surface treatment comprises one or more of physical etching, chemical etching, chemical coating and microbial adsorption. Examples of the chemicals include bovine serum albumin (BSA). The drug delivery system according to the present invention can maximize the effect in the surface treatment having a straightness, such as plasma treatment or chemical vapor deposition.
본 발명의 일측면에서, 상기 미생물은 편모 등을 이용한 이동성, 구체적으로 외부의 자극에 반응하여 그 자극원에 대한 방향성을 가지는 이동성, 즉 주성(taxis)을 가지는 미생물을 포함한다. 더 구체적으로 상기 미생물은 암세포에 대해 주성을 가지는 미생물을 포함한다. 약물 전달 시스템에 상기와 같은 미생물을 흡착시킨 표면 처리가 되어 있는 경우, 흡착된 미생물이 특정 환경 또는 암을 예로 들 수 있는 질병에 반응하여 이동하므로, 그에 의해 약물 전달 시스템이 타겟하는 부위로 이동하게 된다. 본 발명의 다른 일측면에서, 약물 전달 시스템이 타겟 부위에 도달할 때까지 미생물이 약물 전달 시스템에 이동성을 충분히 부여할 수 있도록, 미생물은 스스로 개체 수를 증가시킬 수 있는 미생물일 수 있다. 본 발명의 또 다른 일측면에서, 생분해 속도가 낮은 고분자 외층을 포함하는 약물 전달 시스템의 외면에 미생물을 흡착시키는 경우, 개구부를 통해 약물이 방출되는 중에도 약물 전달 시스템은 외면에 흡착된 미생물에 의한 이동성을 여전히 보유할 수 있다.In one aspect of the invention, the microorganism includes a microorganism having mobility using flagella and the like, specifically, having mobility to the source of stimulation in response to external stimuli, that is, taxis. More specifically, the microorganism includes a microorganism having a main character for cancer cells. If the drug delivery system has a surface treatment in which such microorganisms are adsorbed, the adsorbed microorganisms move in response to a disease such as a specific environment or cancer, thereby causing the drug delivery system to move to a target site. do. In another aspect of the present invention, the microorganism may be a microorganism capable of increasing its own population so that the microorganism can give sufficient mobility to the drug delivery system until the drug delivery system reaches the target site. In another aspect of the present invention, in the case of adsorbing microorganisms on the outer surface of the drug delivery system including a polymer outer layer having a low biodegradation rate, the drug delivery system is mobile by the microorganisms adsorbed on the outer surface while the drug is released through the opening. Can still hold.
본 발명의 또 다른 일측면에서, 미생물은 세균, 구체적으로 에스체리치아 콜리(Escherichia Coli), 세라티아 마르세센스(Serratia Marcescens) 또는 살모넬라 티피뮤리움(Salmonella Typhimurium)을 포함할 수 있으나, 이에 제한되는 것은 아니다.In another aspect of the invention, the microorganism may include bacteria, specifically Escherichia Coli , Serratia Marcescens or Salmonella Typhimurium , but is not limited thereto. It is not.
본 발명의 일측면은 약물층과 약물 방출 조절용 생분해성 고분자층을 번갈아 적층하는 단계를 포함하는 약물 전달 시스템 제조 방법을 제공한다. 상기 약물층과 약물 방출 조절용 생분해성 고분자층을 번갈아 적층하는 단계는 약물과 고분자를 번갈아 주입하는 과정을 포함할 수 있다. 본 발명의 다른 일측면은 고분자 외층을 제조하는 단계; 및 약물층과 약물 방출 조절용 생분해성 고분자층을 번갈아 적층하는 단계를 포함하는 고분자 외층을 포함하는 약물 전달 시스템 제조 방법을 제공한다. 본 발명의 또 다른 일측면은 고분자 외층을 제조하는 단계; 약물층과 약물 방출 조절용 생분해성 고분자층을 번갈아 적층하는 단계; 및 개구부를 덮는 고분자 덮개를 형성하는 단계를 포함하는 고분자 덮개를 포함하는 약물 전달 시스템 제조 방법을 제공한다. 상기 고분자 덮개를 형성하는 단계는 외층의 개구부에 고분자를 미세 주사(micro syringe)로 주입하는 과정을 포함할 수 있다.One aspect of the present invention provides a method for manufacturing a drug delivery system comprising alternately stacking a drug layer and a biodegradable polymer layer for controlling drug release. The step of alternately stacking the drug layer and the biodegradable polymer layer for controlling drug release may include injecting the drug and the polymer alternately. Another aspect of the invention comprises the steps of preparing a polymer outer layer; And it provides a drug delivery system manufacturing method comprising a polymer outer layer comprising the step of alternately laminating the drug layer and the biodegradable polymer layer for controlling drug release. Another aspect of the present invention comprises the steps of preparing a polymer outer layer; Alternately laminating the drug layer and the biodegradable polymer layer for controlling drug release; And it provides a drug delivery system manufacturing method comprising a polymer cover comprising forming a polymer cover covering the opening. The forming of the polymer cover may include injecting the polymer into the opening of the outer layer by a micro syringe.
상기 설명으로부터, 당업자라면 본 발명의 의도 및 범위를 벗어나지 않으면서 여러 용도 및 조건에 적합하도록 본 발명을 다양하게 변경 또는 변형시킬 수 있다. 이러한 변경 또는 변형은 본 발명의 범위에 포함되는 것으로 본다.From the above description, those skilled in the art can variously change or modify the present invention to suit various uses and conditions without departing from the spirit and scope of the present invention. Such changes or modifications are intended to be included within the scope of this invention.

Claims (11)

  1. 약물층과 약물 방출 조절용 생분해성 고분자층이 번갈아 적층되어 있는 층 구조를 포함하는 약물 전달 시스템.A drug delivery system comprising a layer structure in which a drug layer and a biodegradable polymer layer for controlling drug release are alternately stacked.
  2. 제 1 항에 있어서,The method of claim 1,
    층 구조는 2 내지 10개의 층을 포함하는 것을 특징으로 하는 약물 전달 시스템.Drug delivery system, characterized in that the layer structure comprises 2 to 10 layers.
  3. 제 1 항에 있어서,The method of claim 1,
    약물 방출 조절용 생분해성 고분자층은 복수 개이고, 각 고분자층의 고분자는 서로 다른 생분해 속도를 가지는 것을 특징으로 하는 약물 전달 시스템.A plurality of biodegradable polymer layers for controlling drug release, wherein the polymer of each polymer layer has a different biodegradation rate drug delivery system.
  4. 제 1 항에 있어서,The method of claim 1,
    약물 전달 시스템은 층 구조를 감싸는 생분해성 고분자 외층을 더 포함하는 것을 특징으로 하는 약물 전달 시스템.The drug delivery system further comprises a biodegradable polymer outer layer surrounding the layer structure.
  5. 제 4 항에 있어서,The method of claim 4, wherein
    고분자 외층은 개구부를 포함하는 것을 특징으로 하는 약물 전달 시스템.Drug delivery system, characterized in that the polymeric outer layer comprises an opening.
  6. 제 5 항에 있어서,The method of claim 5,
    약물 전달 시스템은 개구부를 덮는 고분자 덮개를 더 포함하고,The drug delivery system further comprises a polymer covering covering the opening,
    상기에서 외층의 고분자, 층 구조 중 약물 방출 조절용 생분해성 고분자층의 고분자 및 덮개의 고분자 순으로 고분자의 생분해 속도가 낮은 것을 특징으로 하는 약물 전달 시스템.The drug delivery system, characterized in that the low biodegradation rate of the polymer in order of the polymer of the outer layer, the polymer of the biodegradable polymer layer for controlling drug release in the layer structure and the polymer of the cover.
  7. 제 6 항에 있어서,The method of claim 6,
    외층의 고분자는 폴리-카프로락톤(poly-caprolactone, PCL) 또는 L-폴리-락타이드(L-poly-lactides, LPLA)를 포함하고,The polymer of the outer layer comprises poly-caprolactone (PCL) or L-poly-lactides (L-poly-lactides, LPLA),
    층 구조 중 고분자층의 고분자는 폴리-글리콜산(poly-glycolic acid, PGA) 또는 폴리-D-락타이드(poly-D-lactide, PDLA)를 포함하며,The polymer of the polymer layer of the layer structure includes poly-glycolic acid (PGA) or poly-D-lactide (poly-D-lactide, PDLA),
    덮개의 고분자는 폴리-락트산(poly-lactic acid, PLA) 또는 폴리-락틱-코-글리콜산(poly-lactic-co-glycolic acid, PLGA)을 포함하는 것을 특징으로 하는 약물 전달 시스템.The drug delivery system is characterized in that the polymer of the cover comprises poly-lactic acid (PLA) or poly-lactic-co-glycolic acid (PLGA).
  8. 제 1 항에 있어서,The method of claim 1,
    약물 전달 시스템은 3 내지 10면체의 형상을 가지는 것을 특징으로 하는 약물 전달 시스템.Drug delivery system, characterized in that it has a shape of 3 to 10 octahedron.
  9. 제 8 항에 있어서,The method of claim 8,
    약물 전달 시스템은 표면 처리가 된 하나 이상의 외면을 포함하는 것을 특징으로 하는 약물 전달 시스템.The drug delivery system includes one or more outer surfaces that have been surface treated.
  10. 제 9 항에 있어서,The method of claim 9,
    표면 처리는 물리적 식각(etching), 화학적 식각, 화학 물질 코팅 및 미생물 흡착 중 하나 이상을 포함하는 것을 특징으로 하는 약물 전달 시스템.Surface treatment comprises drug etching, chemical etching, chemical coating, and microbial adsorption.
  11. 제 10 항에 있어서,The method of claim 10,
    미생물은 에스체리치아 콜리(Escherichia Coli), 세라티아 마르세센스(Serratia Marcescens) 및 살모넬라 티피뮤리움(Salmonella Typhimurium)으로 이루어진 군에서 선택된 하나 이상을 포함하는 것을 특징으로 하는 약물 전달 시스템.The microorganism is a drug delivery system, characterized in that it comprises at least one selected from the group consisting of Escherichia Coli , Serratia Marcescens and Salmonella Typhimurium .
PCT/KR2011/006945 2011-03-11 2011-09-20 Drug delivery system including laminated structure WO2012124869A1 (en)

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KR10-2011-0021973 2011-03-11
KR10-2011-0045827 2011-05-16
KR1020110045827A KR101314127B1 (en) 2011-03-11 2011-05-16 Method for preparing polyhedral drug delivery system
KR10-2011-0045828 2011-05-16
KR1020110045828A KR101345442B1 (en) 2011-03-11 2011-05-16 Drug delivery system comprising laminated structure
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR950003918B1 (en) * 1987-04-06 1995-04-20 알자 코포레이숀 Dosage form comprising parallel laminare
KR20020072290A (en) * 2000-01-20 2002-09-14 델시스 파머수티컬 코포레이션 Multi-step drug dosage forms
KR20100126830A (en) * 2008-03-25 2010-12-02 데이고꾸세이약꾸가부시끼가이샤 Transdermally absorbable preparation

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR950003918B1 (en) * 1987-04-06 1995-04-20 알자 코포레이숀 Dosage form comprising parallel laminare
KR20020072290A (en) * 2000-01-20 2002-09-14 델시스 파머수티컬 코포레이션 Multi-step drug dosage forms
KR20100126830A (en) * 2008-03-25 2010-12-02 데이고꾸세이약꾸가부시끼가이샤 Transdermally absorbable preparation

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