KR20140000841A - Organic-inorganic composite nanoparticles for diagnosis and therapy, and producing the same - Google Patents
Organic-inorganic composite nanoparticles for diagnosis and therapy, and producing the same Download PDFInfo
- Publication number
- KR20140000841A KR20140000841A KR1020120068300A KR20120068300A KR20140000841A KR 20140000841 A KR20140000841 A KR 20140000841A KR 1020120068300 A KR1020120068300 A KR 1020120068300A KR 20120068300 A KR20120068300 A KR 20120068300A KR 20140000841 A KR20140000841 A KR 20140000841A
- Authority
- KR
- South Korea
- Prior art keywords
- nanoparticles
- polyaniline
- present
- mri
- composition
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/12—Macromolecular compounds
- A61K49/122—Macromolecular compounds dimers of complexes or complex-forming compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
- A61K47/6931—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
- A61K49/1878—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles the nanoparticle having a magnetically inert core and a (super)(para)magnetic coating
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S607/00—Surgery: light, thermal, and electrical application
- Y10S607/901—Cancer detection
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
본 발명은 자기 공명 영상을 위한 조영제 역할의 무기 물질과 광열 치료가 가능한 유기물질로 구성된 복합 나노입자 및 그 제조방법 등에 관한 것이다.
The present invention relates to a composite nanoparticle composed of an inorganic material serving as a contrast agent and an organic material capable of photothermal treatment for magnetic resonance imaging, a method for producing the composite nanoparticle, and the like.
암의 치료 가능성을 높이는데 있어서 가장 중요한 것은 암세포의 조기 진단과 그에 따른 적합한 치료이다. 암세포의 조기 진단에 있어서는 암세포가 분화 초기 단계에서 진단하는 것이 매우 중요하다. 이러한 암의 조기 진단에 있어서 나노 입자는 중요한 역할을 담당할 수 있다.The most important thing in increasing the therapeutic potential of cancer is the early diagnosis of cancer cells and the appropriate treatment accordingly. In the early diagnosis of cancer cells, it is very important that the cancer cells diagnose at the early stage of differentiation. Nanoparticles can play an important role in the early diagnosis of these cancers.
나노 입자를 이용하면 그 크기로 인해 암세포에서의 축적이 가능하고 암 특이적인 리간드를 결합시켜서 암을 조기에 진단할 수 있는 가능성이 있다. 상자성 특성을 지닌 산화철 나노 입자의 경우 이미 MRI T2 조영제로서 상용화되어 쓰여지고 있는 실정이다.Using nanoparticles, it is possible to accumulate in cancer cells due to their size, and to bind cancer-specific ligands, which can lead to early diagnosis of cancer. Iron oxide nanoparticles with paramagnetic properties have already been commercialized as MRI T2 contrast agents.
잘 설계된 나노입자는 외과적인 개입 없이 레이저-유도 광원으로 종양위치를 찾아내어 치료할 수 있기 때문에 암을 정확히 진단하고 효과적으로 치료에 접근하는 수단으로서 많은 과학자들의 흥미를 끌고 있다.Well-designed nanoparticles attract many scientists as a means of accurately diagnosing cancer and effectively accessing treatment because it can detect and treat tumor sites with laser-induced light sources without surgical intervention.
진단뿐만 아니라 암의 치료에 있어서도 나노 물질은 앞으로 중요한 역할을 할 것으로 보인다. 최근 들어 비파괴적인 열치료 방법에 대한 연구가 많이 보고되었다. Rice 대학의 Halas 교수와 West 교수 연구팀에서는 금 나노 쉘을 합성하여 이를 열치료에 의한 암세포의 괴사에 응용하였다.Nanomaterials are expected to play an important role in the diagnosis as well as the treatment of cancer. Recently, many studies on non-destructive heat treatment methods have been reported. Halas and West professors at Rice University synthesized gold nanoshells and applied them to necrosis of cancer cells by heat treatment.
한편, 폴리아닐린(Polyaniline; PANI)은 가공성, 안정성, 경제성, 기계적 물성, 전도성이 우수하여 다양한 분야로 응용 가능성이 큰 후보 물질로 인식되었다(Cardillo, L.; wift, D.; Meritt, J. J Imaging Sci Technol 1998, 42,300. 및 Travers, J. P. Synth Met 1990, 35, 159.). 폴리아닐린은 근적외선(Near infrared ray; NIR) 빛을 흡수하면 암-세포 제거를 위해 사용되는 많은 양의 열에너지를 발생시키는 특성이 있다. 폴리아닐린은 염화수소(HCl)에 의해서 양자를 방출하는 염과 산화제로서 암모늄 아황산염을 사용하여 합성한다. 화학적 산화에 의한 중합공정에 의해 진한 초록색의 침전물 ES를 얻고, 이를 다시 수산화나트륨으로 도핑하여 자색의 중합체 분말인 EB를 얻는다. 생체 내외의 양쪽에서 EB(자색) 폴리아닐린 나노입자(Polyaniline nano particle;PANP)는 생물학적 도핑공정에 의해서 NIR빛을 흡수한 ES PANP로 전환된다. NIR 빛에 PANP를 노출시켜 발생된 광열 에너지는 세포 성장과 배양에 필요한 DNA 및/또는 RNA 합성을 차단하는 세포성분을 파괴할 수 있다. 특히 광열 처리는 단백질을 퇴화시키고 세포골격 필라멘트 중합체를 단절시켜 결과적으로 세포를 죽인다. 그러므로 PANPs와 NIR의 조합은 광열에 의한 암-제거가 가능하여 암-치료에 매우 효과적이다(Jaemoon Yang, Jihye Choi, Eun-Kyung Lim and Seungjoo Haam “Convertible Organic Nanoparticles for Near-Infrared Photothermal Ablation of Cancer Cells” Angew. Chem. Int. Ed. 50, 2011, pp.441444).Polyaniline (PANI) has been recognized as a candidate substance having high applicability in various fields due to its excellent processability, stability, economical efficiency, mechanical properties and conductivity (Cardillo, L .; Wift, D .; Meritt, J Imaging Sci Technol 1998, 42, 300 and Travers, JP Synth Met 1990, 35, 159.). Polyaniline absorbs near infrared ray (NIR) light and has the property of generating large amounts of heat energy used for cancer-cell clearance. Polyaniline is synthesized by using a salt that releases both by hydrogen chloride (HCl) and ammonium sulfite as an oxidizing agent. A dark green precipitate ES is obtained by a polymerization process by chemical oxidation, which is doped again with sodium hydroxide to obtain a purple polymer powder EB. EB (purple) polyaniline nanoparticles (PANP) are converted to ES PANP, which absorbs NIR light by biological doping, both in vitro and in vivo. Light heat energy generated by exposure of PANP to NIR light can destroy cell components that block DNA and / or RNA synthesis necessary for cell growth and culture. In particular, photothermal processing degenerates proteins and breaks down cytoskeleton filament polymers, resulting in cell killing. Therefore, the combination of PANPs and NIR is highly effective for cancer-treatment by allowing light-induced cancer-elimination (Jaemoon Yang, Jihye Choi, Eun-Kyung Lim and Seungjoo Haam "Convertible Organic Nanoparticles for Near-Infrared Photothermal Ablation of Cancer Cells "Angew Chem. Int. Ed., 50, 2011, pp. 441444).
본 발명자들은 암세포의 진단과 치료를 효과적으로 동시에 수행할 수 있는 나노 물질에 대해 연구를 계속한 결과, 암 진단에 널리 사용되고 있는 MRI를 이용한 진단과 비파괴적인 근적외선을 이용한 열치료를 동시에 가능케 하는 다기능성 나노 물질을 발명하였다.
As a result of continuing research on nanomaterials capable of simultaneously performing the diagnosis and treatment of cancer cells, the inventors of the present invention have found that multifunctional nano-particles capable of simultaneously performing diagnosis using MRI and heat treatment using nondestructive near- Invented material.
본 발명자들은 MRI를 이용한 진단과 비파괴적인 근적외선을 이용한 열치료를 동시에 가능케 하는 다기능성 나노 물질을 발명하였다. 따라서 본 발명은 폴리아닐린 파티클 표면에 자성체가 부착된 진단 및 치료용 나노입자를 제공하는 것을 목적으로 한다. 또한 상기 나노 입자의 제조 방법 및 이를 포함하는 조성물을 제공하는 것을 그 목적으로 한다.The present inventors invented a multifunctional nanomaterial that enables simultaneous diagnosis using MRI and heat treatment using nondestructive near infrared rays. Accordingly, it is an object of the present invention to provide a diagnostic and therapeutic nanoparticle having a magnetic substance attached to the surface of a polyaniline particle. It is another object of the present invention to provide a method for producing the nanoparticles and a composition containing the nanoparticles.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.
However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.
본 발명은 폴리아닐린 파티클 표면에 자성체가 부착된, 진단 및 치료용 나노 입자를 제공한다.The present invention provides diagnostic and therapeutic nanoparticles having a magnetic substance attached to the surface of a polyaniline particle.
본 발명의 일 구현예로서, 상기 나노 입자는 자기 공명 영상 장치(Magnetic Resonance Imaging;MRI)용 조영제 및 광열치료제 기능을 갖는 것을 특징으로 한다.In one embodiment of the present invention, the nanoparticles are characterized by having a function as a contrast agent for Magnetic Resonance Imaging (MRI) and a photothermal therapeutic agent.
또한 본 발명은 Also,
a) 블록 공중합체를 제조하는 단계;a) preparing a block copolymer;
b) 상기 블록 공중합체를 폴리아닐린에 처리하는 단계; b) treating the block copolymer with polyaniline;
c) 상기 폴리아닐린이 파티클화되는 단계;및c) particle-forming the polyaniline; and
d) 상기 폴리아닐린 파티클 표면에 자성체를 부착시키는 단계를 포함하는, 나노 입자의 제조 방법을 제공한다.d) attaching a magnetic substance to the surface of the polyaniline particle.
본 발명의 일 구현예로서, a)단계는 다이 에틸렌 테트라아민 펜타-아세트산(diethylene tetraamine penta-acetic acid)에 계면활성제를 첨가하여 제조하는 것을 특징으로 한다. 그러나 블록 공중합체의 제조 방법은 이에 제한되지 않는다.In one embodiment of the present invention, step a) is characterized in that a surfactant is added to diethylene tetraamine penta-acetic acid. However, the production method of the block copolymer is not limited thereto.
본 발명의 다른 구현예로서, 상기 계면활성제는 폴리소베이트 80 (polysorbate 80)인 것을 특징으로 한다. 그러나 계면활성제의 종류는 이에 제한되지 않는다.In another embodiment of the present invention, the surfactant is polysorbate 80. However, the kind of the surfactant is not limited thereto.
본 발명의 또 다른 구현예로서, d)단계의 자성체는 Fe3O4, Fe2O4, 및 MnFe2O4로 이루어지는 군으로부터 선택되는 것임을 특징으로 한다. 그러나 자성체의 종류는 이에 제한되지 않으며, MRI용 T1 조영제 또는 T2 조영제로 작용할 수 있는 자성체를 모두 포함한다.According to another embodiment of the present invention, the magnetic substance in step d) is selected from the group consisting of Fe 3 O 4 , Fe 2 O 4 , and MnFe 2 O 4 . However, the type of the magnetic substance is not limited thereto, and it includes all the magnetic substances capable of acting as T1 contrast medium for MRI or T2 contrast medium.
본 발명의 또 다른 구현예로서, d)단계의 나노 입자는 자기 공명 영상 장치(MRI)용 조영제 및 광열치료제 기능을 갖는 것을 특징으로 한다.In another embodiment of the present invention, the nanoparticle of step d) is characterized by having a function as a contrast agent and a photo-thermal treatment agent for a magnetic resonance imaging (MRI) apparatus.
또한 본 발명은 폴리아닐린 파티클 표면에 자성체가 부착된 복합 나노입자 및 가능한 담체를 포함하는 약학적 조성물을 제공한다.The present invention also provides a pharmaceutical composition comprising a complex nanoparticle to which a magnetic substance is attached on the surface of a polyaniline particle and a possible carrier.
본 발명의 일 구현예로서, 상기 조성물은 세포증식성 질병 또는 종기의 치료용으로 사용하는 것을 특징으로 한다. 그러나 본 발명의 조성물로 치료 가능한 질병은 이에 제한되지 않으며, 광열치료로 치료 가능한 질병을 모두 포함한다. In one embodiment of the present invention, the composition is characterized in that it is used for the treatment of cell proliferative diseases or offspring. However, the diseases treatable with the composition of the present invention are not limited thereto, and include all diseases treatable by photothermal therapy.
또한 본 발명은 Also,
a) 상기 조성물을 개체에 주입하는 단계; a) injecting the composition into a subject;
b) 자기 공명 영상 장치(MRI)를 이용하여 상기 조성물에 의해 발산되는 영상을 확인하여 표적 부위를 확인하는 단계; 및 b) confirming the target region by confirming the image emitted by the composition using a magnetic resonance imaging (MRI) apparatus; And
c) 상기 표적 부위에 근적외선을 조사시킴으로써 열을 발생시켜 표적 부위에 존재하는 세포를 사멸시키는 단계를 포함하는 진단 및 광열치료방법을 제공한다.c) generating heat by irradiating the target site with near-infrared light to kill cells present in the target site.
본 발명의 일 구현예로서, 상기 b)단계는 세포증식성 질병을 진단하고 치료하기 위한 것임을 특징으로 한다. 그러나 본 발명의 조성물을 이용하여 진단하고 치료할 수 있는 질병은 이에 제한되지 않으며, MRI를 사용하여 진단하고 광열치료로 치료할 수 있는 질병을 모두 포함한다. In one embodiment of the present invention, the step b) is for diagnosing and treating cell proliferative diseases. However, the diseases that can be diagnosed and treated using the composition of the present invention are not limited thereto, and include all diseases that can be diagnosed using MRI and treated with photothermal therapy.
본 발명의 나노 입자를 이용한 MRI 용 조영제 및 광열치료제는 MRI를 이용한 진단을 동시에 할 수 있고 낮은 세기의 에너지를 조사하여도 국소적인 열을 낼 수 있다. 따라서 암을 조기 진단 후 비침습적으로 국소적인 부위에 집중적인 치료를 하는 데 중요하게 응용될 수 있을 것으로 기대된다.
The contrast agent and photothermal therapeutic agent using the nanoparticles of the present invention can simultaneously perform diagnosis using MRI and can generate local heat even when irradiated with low intensity energy. Therefore, it is expected to be an important application for intensive treatment of localized areas non-invasively after early diagnosis of cancer.
도 1은 본원 발명의 나노 입자의 제조 공정의 모식도이다.
도 2는 (a) 도핑된 본 발명 나노입자 (MDPANI)의 흡광 스펙트럼, (b) 본 발명 나노입자 (MDPANI)의 크기를 측정한 결과이다.
도 3은 본 발명 나노입자인 유-무기복합 폴리아닐린 나노파티클의 투과전자현미경 사진 결과이다. 1 is a schematic view of a process for producing nanoparticles of the present invention.
FIG. 2 shows the absorption spectra of (a) the doped nanoparticles of the present invention (MDPANI) and (b) the results of measuring the sizes of the nanoparticles of the present invention (MDPANI).
FIG. 3 is a transmission electron microscope photograph of the organic-inorganic composite polyaniline nanoparticles of the present invention nanoparticles.
본 명세서에서 블록 공중합체란 두가지 이상의 고분자가 공유결합으로 서로 연결되어 있는 구조로 자기조립성질을 가지고 있어 원자간의 공유결합으로 이루어진 고분자가 분자 간의 상호인력에 의하여 특정 나노구조를 자발적으로 형성할 수 있도록 하는 물질을 말한다.In the present specification, a block copolymer is a structure in which two or more polymers are covalently bonded to each other and has a self-assembling property so that a polymer having a covalent bond between atoms can form a specific nano structure by mutual attraction between molecules .
본 명세서에서 자기공명영상(MRI, Magnetic Resonance Image)은 자기장 안에서 수소 원자의 스핀이 이완되는 현상을 이용해 신체의 생화학적 정보를 영상으로 얻는 방법이다. 자기 또는 전파는 골에 방해를 받지 않기 때문에 단단한 골 주위 또는 뇌나 골수의 종양에 대하여 종단, 횡단, 임의의 각도에서 선명한 입체적인 단층상을 얻을 수 있다.In the present specification, magnetic resonance imaging (MRI) is a method of acquiring biochemical information of a body by using a phenomenon in which a spin of a hydrogen atom is relaxed in a magnetic field. Since the magnetic or radio waves are not disturbed by the bone, a sharp three-dimensional tomographic image can be obtained at the end, transverse, or any angle with respect to the hard bone around or the brain or the bone marrow.
본 명세서에서 나노입자란 크기가 수 내지 수백 나노미터(nm, 10억분의 1 미터인 물질, 크기로 인해 원자와 벌크물질의 중간적인 성질을 갖는다)인 입자를 말한다.As used herein, nanoparticle refers to particles having a size in the range of several to several hundred nanometers (nm, a material having an atomic weight of one billionth of a meter and having an intermediate property between atoms and bulk materials due to its size).
본 명세서에서의 조영제란 MRI 검사시에 조직간의 음영 대비를 증가시키는 물질을 말한다. MRI 조영제의 종류에는 T1 조영제와 T2 조영제가 있다. T1 조영제는 T1 이완시에 조직간의 음영대비를 증가시키는 물질로 가돌리늄 제제인 Gd-DTPA 나 망간 제제인 Mn-DTPA 등 금속 이온 착화물이 사용되고 있다. T2 조영제는 T2 이완시에 조직간의 음영대비를 증가시키는 물질로 현재 자성을 띄는 산화철 제제인 Feridex 등이 사용되고 있다.In the present specification, the contrast agent refers to a substance that increases contrast between tissues during MRI examination. Types of MRI contrast agents include T1 contrast agents and T2 contrast agents. T1 contrast agents are metal ion complexes such as Gd-DTPA, which is a gadolinium agent, and Mn-DTPA, which is a manganese agent, in order to increase contrast between tissues during T1 relaxation. T2 contrast agent is Feridex which is an iron oxide preparation which is now magnetic and which increases contrast between tissues during T2 relaxation.
본 발명에 따른 조성물은 의약 분야에서 통상적으로 이용되는 경로를 통해 투여될 수 있으며, 비경구 투여가 바람직하고 예를 들어 정맥내, 복강내, 근육내, 피하 또는 국부 경로를 통하여 투여할 수 있다.The composition according to the present invention may be administered through a route commonly used in the medical field, and parenteral administration is preferred and may be administered, for example, intravenously, intraperitoneally, intramuscularly, subcutaneously or via a local route.
본 발명에 따른 조성물에 사용되는 담체는 의약 분야에서 통상 사용되는 담체 및 비히클을 포함한다. 본 발명의 조성물에 사용될 수 있는 약제학적으로 허용되는 담체로는 이들로 한정되는 것은 아니지만 이온교환, 알루미나, 알루미늄 스테아레이트, 레시틴, 혈청 단백질, 완충 물질, 물, 염 또는 전해질, 교질성 실리카, 마그네슘 트리실리케이트, 폴리비닐피롤리돈, 셀룰로즈계 기질, 폴리에틸렌 글리콜, 나트륨 카르복시메틸셀룰로즈, 폴리아릴레이트, 왁스, 폴리에틸렌 글리콜 및 양모지 등이 포함된다. 본 발명의 조성물은 상기 성분들 이외에 윤활제, 습윤제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다.The carrier used in the composition according to the present invention includes a carrier and a vehicle commonly used in the medical field. Pharmaceutically acceptable carriers that can be used in the compositions of the present invention include but are not limited to ion exchange, alumina, aluminum stearate, lecithin, serum proteins, buffer substances, water, salts or electrolytes, colloidal silicas, magnesium Trisilicate, polyvinylpyrrolidone, cellulose-based substrate, polyethylene glycol, sodium carboxymethylcellulose, polyarylate, wax, polyethylene glycol and wool. The composition of the present invention may further comprise a lubricant, a wetting agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components.
한 양태로서, 본 발명에 따른 조성물은 비경구 투여를 위한 수용성 용액으로 제조할 수 있다. 바람직하게는 한스 용액(Hank's solution), 링거 용액(Ringer's solution) 또는 물리적으로 완충된 염수와 같은 완충용액을 사용할 수 있다. 수용성 주입 현탁액은 소디움 카르복시메틸셀룰로즈, 솔비톨 또는 덱스트란과 같이 현In one embodiment, the composition according to the invention may be prepared in an aqueous solution for parenteral administration. Preferably, a buffer solution such as Hanks' solution, Ringer's solution, or physically buffered saline may be used. Water-soluble injection suspensions may contain, for example, sodium carboxymethylcellulose, sorbitol or dextran,
탁액의 점도를 증가시킬 수 있는 기질을 첨가할 수 있다.Substrates capable of increasing the viscosity of the suspension can be added.
본 발명의 바람직한 조성물은 멸균 주사용 수성 또는 유성 현탁액으로서 멸균 주사용 제제의 형태일 수 있다. 이러한 현탁액은 적합한 분산제 또는 습윤제 및 현탁화제를 사용하여 본 분야에 공지된 기술에 따라 제형될 수 있다. 멸균 주사용 제제는 또한 무독성의 비경구적으로 허용되는 희석제 또는 용매 중의 멸균 주사 용액 또는 현탁액일 수 있다. 사용될 수 있는 비히클 및 용매로는 만니톨, 물, 링거 용액 및 등장성 염화나트륨 용액이 있다. 또한, 멸균 비휘발성 오일이 통상적으로 용매 또는 현탁화 매질로서 사용된다. 이러한 목적을 위해 합성 모노 또는 디글리세라이드를 포함하여 자극성이 적은 비휘발성 오일을 사용할 수 있다.A preferred composition of the present invention can be in the form of a sterile injectable preparation as a sterile injectable aqueous or oily suspension. Such suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent. Vehicles and solvents that may be used include mannitol, water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, nonvolatile oils are conventionally used as a solvent or suspending medium. For this purpose it is possible to use non-irritating non-volatile oils, including synthetic mono or diglycerides.
본원 발명의 나노 입자 또는 이를 포함하는 조성물은 다음의 단계를 거쳐 진단 및 치료에 응용할 수 있다. The nanoparticles of the present invention or a composition containing the nanoparticles of the present invention can be applied to diagnosis and treatment through the following steps.
즉, (1) 전술된 양태의 나노입자와 약제학적으로 허용되는 담체를 포함한 조성물을 검체에 주입하는 단계; (1) injecting a sample into a composition comprising a nanoparticle of the above-described mode and a pharmaceutically acceptable carrier;
(2) 검체로부터 MRI상에서 상기 나노입자에 의해 발산되는 영상을 확인하여 표적 부위를 확인하는 단계; 및 (2) confirming an image emitted from the specimen by the nanoparticles on the MRI to identify a target site; And
(3) 표적 부위에 근적외선을 조사시킴으로써 열을 발생시켜 표적 부위에 존재하는 세포를 사멸시켜 표적 부위를 치료하는 단계를 포함한 질병의 진단 및 치료방법을 제공한다.(3) A method for diagnosis and treatment of diseases including a step of generating heat by irradiating near infrared rays to a target site to kill cells present in the target site and treating the target site.
여기서, 단계 (1)을 거쳐 단계 (2)에서 종료된다면 질병의 진단만이 이루어진 것이며, 단계 (1) 및(2)를 거쳐 단계 (3)까지 진행된다면 질병의 진단과 치료가 모두 이루어질 수 있다.Here, if only the diagnosis of the disease is made if it is finished in the step (2) through the step (1), and if it goes to the step (3) through the steps (1) and (2) .
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.
Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.
[[ 실시예Example ]]
실시예 1. 블록 공중합체의 합성Example 1. Synthesis of block copolymer
다이 에틸렌 테트라아민 펜타-아세틱 산과 계면활성제인 폴리소베이트 80을 사용하여 블록 공중합체를 합성하였다. 다이 에틸렌 테트라아민 펜타-아세틱 산 4.5 mmol과 폴리소베이트80 1.5 mmol을 다이메틸설폭시드 용액에 용해시키고, 80℃로 24시간 동안 반응 시켰다. 이 용액을 일주일 동안 투석시킨 후 동결건조하였다.
A block copolymer was synthesized using diethylene tetraamine penta-acetic acid and polysorbate 80 as a surfactant. 4.5 mmol of diethylenetetraamine penta-acetic acid and 1.5 mmol of Polysorbate 80 were dissolved in a dimethylsulfoxide solution and reacted at 80 DEG C for 24 hours. This solution was dialyzed for one week and then lyophilized.
실시예 2. 폴리아닐린의 파티클화 및 자성체의 부착Example 2. Partialization of polyaniline and attachment of magnetic material
실시예 1에서 만들어진 300 mg의 블록 공중합체를 20 mL 증류수에 분산시킨 후 교반한 다음, 폴리아닐린 10mg을 1.5 mL 노말 메틸 피롤리돈 용액에 용해시킨 것을 첨가하였다. 이 과정을 통해 수상에 분산되지 않는 폴리아닐린을 수상에 안정되게 분산되게 하여 파장 800 nm에서 최대 흡광을 가지는 지름 100 nm 크기의 폴리아닐린 파티클을 만들었다. 그런 다음 10 mg의 MnFe2O4자성체를 넣어준 후 24 시간 동안 교반하고, 원심분리를 통하여 정제하였다. 이 과정을 통해 조영제 역할이 가능한 지름 12 nm 크기의 자성체가 폴리아닐린 파티클 표면에 부착되었다.300 mg of the block copolymer prepared in Example 1 was dispersed in 20 mL of distilled water and stirred. Then, 10 mg of polyaniline dissolved in 1.5 mL of normal methylpyrrolidone solution was added. Through this process, the polyaniline which is not dispersed in the water phase was stably dispersed in the water phase, and polyaniline particles having a diameter of 100 nm and having the maximum absorption at a wavelength of 800 nm were produced. Then, 10 mg of MnFe 2 O 4 magnetic substance was added thereto, followed by stirring for 24 hours and purification by centrifugation. Through this process, a 12 nm diameter magnetic substance capable of acting as a contrast agent was attached to the surface of the polyaniline particle.
도 3에서 코어부분에 폴리아닐린 파티클 표면에 자성체가 안정적으로 부착됨을 확인할 수 있다.
3, it can be confirmed that the magnetic substance is stably attached to the surface of the polyaniline particle in the core portion.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술 분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며, 한정적이 아닌 것으로 이해해야 한다.
It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. Therefore, the above-described embodiments are to be understood in all respects as illustrative and not restrictive.
Claims (11)
Diagnostic and therapeutic nanoparticles having a magnetic body attached to a polyaniline particle surface.
상기 나노 입자는 자기 공명 영상 장치(Magnetic Resonance Imaging;MRI)용 조영제 및 광열치료제 기능을 갖는 것을 특징으로 하는, 나노입자.
The method of claim 1,
The nanoparticles, characterized in that the magnetic resonance imaging device (Magnetic Resonance Imaging; MRI) has a contrast agent and a photothermal therapeutic agent, nanoparticles.
b) 상기 블록 공중합체를 폴리아닐린에 처리하는 단계;
c) 상기 폴리아닐린이 파티클화되는 단계; 및
d) 상기 폴리아닐린 파티클 표면에 자성체를 부착시키는 단계를 포함하는, 나노 입자의 제조 방법.
a) preparing a block copolymer;
b) treating the block copolymer with polyaniline;
c) particle-forming the polyaniline; And
d) attaching a magnetic material to the polyaniline particle surface.
a)단계는 다이 에틸렌 테트라아민 펜타-아세트산(diethylene tetraamine penta-acetic acid )에 계면활성제를 첨가하여 블록 공중합체를 제조하는 것을 특징으로 하는, 나노 입자의 제조 방법.
The method of claim 3, wherein
Step a) is a method for producing nanoparticles, characterized in that the block copolymer is prepared by adding a surfactant to diethylene tetraamine penta-acetic acid (diethylene tetraamine penta-acetic acid).
상기 계면활성제는 폴리소베이트 80 (polysorbate 80)인 것을 특징으로 하는, 제조 방법.
5. The method of claim 4,
The surfactant is polysorbate 80 (polysorbate 80), characterized in that the manufacturing method.
d)단계의 자성체는 Fe3O4, Fe2O4, 및 MnFe2O4로 이루어지는 군으로부터 선택되는 것임을 특징으로 하는, 제조 방법.
The method of claim 3, wherein
The magnetic body of step d) is characterized in that it is selected from the group consisting of Fe 3 O 4 , Fe 2 O 4 , and MnFe 2 O 4 .
상기 나노 입자는 자기 공명 영상 장치(MRI)용 조영제 및 광열치료제 기능을 갖는 것을 특징으로 하는, 제조 방법.
The method of claim 3, wherein
The nanoparticles are characterized in that the magnetic resonance imaging device (MRI) contrast agent and photothermal therapeutic agent function.
A pharmaceutical composition comprising nanoparticles having a magnetic body attached to a polyaniline particle surface and a possible carrier.
상기 조성물은 세포증식성 질병 또는 종기의 치료용으로 사용하는 것을 특징으로 하는, 조성물.
The method of claim 8,
The composition, characterized in that used for the treatment of cell proliferative diseases or boils.
b) 자기 공명 영상 장치(MRI)를 이용하여 상기 조성물에 의해 발산되는 영상을 확인하여 표적 부위를 확인하는 단계; 및
c) 상기 표적 부위에 근적외선을 조사시킴으로써 열을 발생시켜 표적 부위에 존재하는 세포를 사멸시키는 단계를 포함하는, 진단 및 광열치료방법.
a) injecting the composition of claim 8 into a subject;
b) identifying a target site by checking an image emitted by the composition using a magnetic resonance imaging device (MRI); And
c) generating heat by irradiating the target site with near-infrared rays to kill cells present at the target site.
상기 방법은 세포증식성 질병을 진단하고 치료하기 위한 것임을 특징으로 하는, 진단 및 광열치료방법.
The method of claim 10,
The method is characterized in that for diagnosing and treating cell proliferative diseases, diagnostic and photothermal treatment method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020120068300A KR101432364B1 (en) | 2012-06-26 | 2012-06-26 | Organic-inorganic composite nanoparticles for diagnosis and therapy, and producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020120068300A KR101432364B1 (en) | 2012-06-26 | 2012-06-26 | Organic-inorganic composite nanoparticles for diagnosis and therapy, and producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20140000841A true KR20140000841A (en) | 2014-01-06 |
| KR101432364B1 KR101432364B1 (en) | 2014-08-20 |
Family
ID=50138571
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020120068300A KR101432364B1 (en) | 2012-06-26 | 2012-06-26 | Organic-inorganic composite nanoparticles for diagnosis and therapy, and producing the same |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101432364B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101384977B1 (en) * | 2013-08-20 | 2014-04-21 | 연세대학교 산학협력단 | Nmps solubilization apparatus having coaxial nozzle |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100796985B1 (en) | 2006-06-30 | 2008-01-22 | 연세대학교 산학협력단 | Multi-Functional Nanoparticles Partially-Deposited with Gold Film |
-
2012
- 2012-06-26 KR KR1020120068300A patent/KR101432364B1/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101384977B1 (en) * | 2013-08-20 | 2014-04-21 | 연세대학교 산학협력단 | Nmps solubilization apparatus having coaxial nozzle |
Also Published As
| Publication number | Publication date |
|---|---|
| KR101432364B1 (en) | 2014-08-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Su et al. | Cetuximab-conjugated iodine doped carbon dots as a dual fluorescent/CT probe for targeted imaging of lung cancer cells | |
| Cheng et al. | PEGylated Prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy | |
| Tian et al. | Poly (acrylic acid) bridged gadolinium metal–organic framework–gold nanoparticle composites as contrast agents for computed tomography and magnetic resonance bimodal imaging | |
| Zhang et al. | Graphene oxide-BaGdF5 nanocomposites for multi-modal imaging and photothermal therapy | |
| Chen et al. | Fabrication of fluorescent nanoparticles based on AIE luminogens (AIE dots) and their applications in bioimaging | |
| Zhou et al. | Gadolinium complex and phosphorescent probe-modified NaDyF4 nanorods for T1-and T2-weighted MRI/CT/phosphorescence multimodality imaging | |
| Liu et al. | Manganese (II) chelate functionalized copper sulfide nanoparticles for efficient magnetic resonance/photoacoustic dual-modal imaging guided photothermal therapy | |
| Shi | Integrated multifunctional nanosystems for medical diagnosis and treatment | |
| Nafiujjaman et al. | Ternary graphene quantum dot–polydopamine–Mn 3 O 4 nanoparticles for optical imaging guided photodynamic therapy and T 1-weighted magnetic resonance imaging | |
| Zhang et al. | Sub-10 nm water-dispersible β-NaGdF4: X% Eu3+ nanoparticles with enhanced biocompatibility for in vivo x-ray luminescence computed tomography | |
| Wang et al. | Targeted and imaging-guided chemo-photothermal ablation achieved by combining upconversion nanoparticles and protein-capped gold nanodots | |
| Yin et al. | Folic acid-conjugated organically modified silica nanoparticles for enhanced targeted delivery in cancer cells and tumor in vivo | |
| Liu et al. | Microwave-assisted one-step rapid synthesis of near-infrared gold nanoclusters for NIRF/CT dual-modal bioimaging | |
| CN105363043A (en) | RGD-labeled fluorescent gold nano-cluster preparation method | |
| Chen et al. | Facile synthesis of β-lactoglobulin capped Ag 2 S quantum dots for in vivo imaging in the second near-infrared biological window | |
| Du et al. | Improving the MR imaging sensitivity of upconversion nanoparticles by an internal and external incorporation of the Gd3+ strategy for in vivo tumor-targeted imaging | |
| Chen et al. | Nanoparticle probes for structural and functional photoacoustic molecular tomography | |
| Ma et al. | Image-guided selection of Gd@ C-dots as sensitizers to improve radiotherapy of non-small cell lung cancer | |
| KR101507645B1 (en) | Organic/inorganic nanocomposite for diagnosis and treatment of cancer | |
| Yin et al. | Fluorescent oligo (p-phenyleneethynylene) contained amphiphiles-encapsulated magnetic nanoparticles for targeted magnetic resonance and two-photon optical imaging in vitro and in vivo | |
| US20180161461A1 (en) | Rare Earth Oxide Particles and Use Thereof in Particular In Imaging | |
| Cai et al. | Exfoliation and in situ functionalization of MoS2 nanosheets for MRI-guided combined low-temperature photothermal therapy and chemotherapy | |
| Shang et al. | Synergistic effect of oxygen-and nitrogen-containing groups in graphene quantum dots: Red emitted dual-mode magnetic resonance imaging contrast agents with high relaxivity | |
| Kim et al. | Dynamic Nuclear Polarization of Selectively 29Si-Enriched Core@ shell Silica Nanoparticles | |
| US9782499B2 (en) | Block copolymer (BCP) encapsulated nanoparticles and methods of use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| N231 | Notification of change of applicant | ||
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| GRNT | Written decision to grant | ||
| LAPS | Lapse due to unpaid annual fee |