WO2012124869A1 - Système d'administration de médicament comprenant une structure stratifiée - Google Patents

Système d'administration de médicament comprenant une structure stratifiée 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
Authority
WO
WIPO (PCT)
Prior art keywords
delivery system
polymer
drug delivery
drug
layer
Prior art date
Application number
PCT/KR2011/006945
Other languages
English (en)
Korean (ko)
Inventor
조동일
홍석준
이상민
안재현
유형정
Original Assignee
서울대학교산학협력단
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.)
Filing date
Publication date
Priority claimed from KR1020110045826A external-priority patent/KR101314126B1/ko
Priority claimed from KR1020110045827A external-priority patent/KR101314127B1/ko
Priority claimed from KR1020110045828A external-priority patent/KR101345442B1/ko
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/fr

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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.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

Selon un aspect, la présente invention porte sur un système d'administration de médicament comprenant une structure feuilletée où une couche de médicament et une couche de polymère biodégradable pour commander la libération de médicaments sont laminées de manière alternée. Le système d'administration de médicament peut commander facilement une vitesse de libération de médicament in vivo et une quantité de libération.
PCT/KR2011/006945 2011-03-11 2011-09-20 Système d'administration de médicament comprenant une structure stratifiée WO2012124869A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US14/004,670 US9351924B2 (en) 2011-03-11 2011-09-20 Drug delivery system including laminated structure
US14/004,670 US20140005600A1 (en) 2011-03-11 2012-09-20 Drug delivery system including laminated structure

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
KR10-2011-0021973 2011-03-11
KR10-2011-0021981 2011-03-11
KR20110021981 2011-03-11
KR20110021973 2011-03-11
KR20110021971 2011-03-11
KR10-2011-0021971 2011-03-11
KR1020110045826A KR101314126B1 (ko) 2011-03-11 2011-05-16 다면체 형상의 약물 전달 시스템
KR1020110045827A KR101314127B1 (ko) 2011-03-11 2011-05-16 다면체 형상의 약물 전달 시스템 제조 방법
KR10-2011-0045828 2011-05-16
KR10-2011-0045826 2011-05-16
KR1020110045828A KR101345442B1 (ko) 2011-03-11 2011-05-16 적층 구조를 포함하는 약물 전달 시스템
KR10-2011-0045827 2011-05-16

Publications (1)

Publication Number Publication Date
WO2012124869A1 true WO2012124869A1 (fr) 2012-09-20

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Application Number Title Priority Date Filing Date
PCT/KR2011/006945 WO2012124869A1 (fr) 2011-03-11 2011-09-20 Système d'administration de médicament comprenant une structure stratifiée

Country Status (1)

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WO (1) WO2012124869A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR950003918B1 (ko) * 1987-04-06 1995-04-20 알자 코포레이숀 박막적층배열로 구성된 제형
KR20020072290A (ko) * 2000-01-20 2002-09-14 델시스 파머수티컬 코포레이션 다단계 약물 투여 형태
KR20100126830A (ko) * 2008-03-25 2010-12-02 데이고꾸세이약꾸가부시끼가이샤 경피 흡수 제제

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR950003918B1 (ko) * 1987-04-06 1995-04-20 알자 코포레이숀 박막적층배열로 구성된 제형
KR20020072290A (ko) * 2000-01-20 2002-09-14 델시스 파머수티컬 코포레이션 다단계 약물 투여 형태
KR20100126830A (ko) * 2008-03-25 2010-12-02 데이고꾸세이약꾸가부시끼가이샤 경피 흡수 제제

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