TWI722061B - 磁性元素離子植入奈米鑽石內以形成用於醫療用途之組成物 - Google Patents
磁性元素離子植入奈米鑽石內以形成用於醫療用途之組成物 Download PDFInfo
- Publication number
- TWI722061B TWI722061B TW105139122A TW105139122A TWI722061B TW I722061 B TWI722061 B TW I722061B TW 105139122 A TW105139122 A TW 105139122A TW 105139122 A TW105139122 A TW 105139122A TW I722061 B TWI722061 B TW I722061B
- Authority
- TW
- Taiwan
- Prior art keywords
- composition
- magnetic
- ion implantation
- nanodiamond
- nano
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B34/00—Computer-aided surgery; Manipulators or robots specially adapted for use in surgery
- A61B34/70—Manipulators specially adapted for use in surgery
- A61B34/73—Manipulators for magnetic surgery
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- 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
- A61K47/6941—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 granulate or an agglomerate
-
- 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
-
- 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
-
- 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
- A61K49/1827—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 having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/183—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 having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an inorganic material or being composed of an inorganic material entrapping the MRI-active nucleus, e.g. silica core doped with a MRI-active nucleus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N2/00—Magnetotherapy
- A61N2/004—Magnetotherapy specially adapted for a specific therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
- C23C14/06—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the coating material
- C23C14/14—Metallic material, boron or silicon
- C23C14/18—Metallic material, boron or silicon on other inorganic substrates
-
- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
- C23C14/22—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
- C23C14/48—Ion implantation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/36—Image-producing devices or illumination devices not otherwise provided for
- A61B90/37—Surgical systems with images on a monitor during operation
- A61B2090/374—NMR or MRI
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F2007/009—Heating or cooling appliances for medical or therapeutic treatment of the human body with a varying magnetic field acting upon the human body, e.g. an implant therein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/02—Compresses or poultices for effecting heating or cooling
- A61F2007/0261—Compresses or poultices for effecting heating or cooling medicated
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Nanotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Surgery (AREA)
- Radiology & Medical Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Metallurgy (AREA)
- Mechanical Engineering (AREA)
- Materials Engineering (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Vascular Medicine (AREA)
- Robotics (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Plasma & Fusion (AREA)
- Otolaryngology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Magnetic Treatment Devices (AREA)
- Medicinal Preparation (AREA)
Abstract
本發明提供一種用於醫療用途之組成物及其製備方法。該組成物包含至少一磁性奈米粒子包括一奈米鑽石和至少一磁性元素,其中該至少一磁性元素是藉由一離子佈植系統嵌入至該至少一奈米鑽石內。該奈米鑽石可與不同的成分合成以增進該組成物之醫療效果。
Description
本發明是關於一種用於醫療用途之組成物及其製備方法,尤其是關於一種藉由將磁性元素以離子植入技術植入奈米鑽石內以形成磁性奈米粒子,其中該磁性奈米粒子可被作為一組成物以進一步使用在各種醫療目的中。
近來,關於治療癌症病患之研究的領域,已致力於發展藉由磁性奈米粒子在體內產生局部的熱效應。多年來,科學家們已做過很多研究和發表有關使用熱治療的潛力,其可用於治療或縮小腫瘤。利用熱能來破壞癌症腫瘤的高溫治療(Hyperthermia therapy)已被廣泛地應用於癌症治療中。在高溫治療中(即,在癌症治療中使用高溫治療法)可發揮將癌細胞加熱的效果是已知的,故可藉由電磁場直接將該磁性奈米粒子加熱以將熱能集中在局部部位,進而使得癌細胞處的溫度上升。並且,當同時結合熱能與放射能時,從病患存活率和腫瘤消退的成效評估來看,其是優異的。一般而言,在細胞單獨暴露在熱能或者是同時暴露在熱能與放射能結合的情況下,正常細胞的復原能力會快於癌症細胞。此外,相較於癌症組織,正常的組織具有較多的血流量,使得正常組織可較快地將熱能疏散,故此
特點有利於進行結合熱能與放射能的癌症治療方法。
在傳統的高溫治療中,磁性的鐵或氧化鐵奈米粒子,例如三氧化二鐵(Fe2O3)、四氧化三鐵(Fe3O4)、鐵(Fe)等等之奈米粒子,其可與標靶藥物合成以進行高溫治療。將磁性的鐵或氧化鐵奈米粒子導向癌症細胞,接著藉由將奈米粒子暴露到交流射頻磁場中以誘導它們產生熱能,使得癌細胞被來自於磁性的鐵或氧化鐵奈米粒子因磁滯損耗(hysteresis loss)而產生的熱能加熱。
然而,上述的磁性鐵或氧化鐵奈米粒子具有數個缺點,包括細胞毒性和較差的生物相容性。並且,由於該磁性鐵或氧化鐵奈米粒子在表面具有少數碳氫鍵(carbon-hydrogen bond)或離子鍵,因此難以將大量的化療藥物或標靶媒介與該磁性鐵或氧化鐵奈米粒子合成。有鑑於此,有必要提供一種新型的磁性奈米粒子,其應用在醫療用途中具有毒性較小的副作用,並且能輕易地與大量的化療藥物或標靶媒介合成以解決習知技術中存在的問題。
為了解決上述技術問題,本發明之一目的在於提供一種組成物及其製備方法。該組成物包含磁性奈米粒子,其是藉由離子佈值技術將磁性元素嵌入奈米鑽石內而形成。該組成物還可進一步與靶向媒介合成,藉此將該組成物傳遞至腫瘤細胞以進行高溫治療。並且,在該組成物內的該磁性奈米粒子可供核磁共振造影(magnetic resonance imaging,MRI)使用,以精確地診斷腫瘤的位置和分布。因此,利用核磁共振造影可監測組成物通過與靶向媒介合成後的傳遞能力,藉此判斷是否有足夠濃度的組成
物到達在主體內的一目標位置以發揮適當的治療效果。此外,該組成物可進一步與其他的醫療媒介合成,例如抗菌劑,使得該組成物可藉由施加一外部磁場而被引導至集中在主體內的一目標側,以治療細菌感染或者是其他的疾病。
為了達到上述目的,本發明提供一種用於醫療用途的組成物,包含:至少一磁性奈米粒子,包括一奈米鑽石和至少一磁性元素,其中該至少一磁性元素是藉由一離子佈植系統及離子佈值技術嵌入至該至少一奈米鑽石內。
在本發明之一較佳實施例中,該至少一磁性元素選自於由鐵(Fe)、錳(Mn)、鈷(Co)、以及鎳(Ni)元素所組成的群組。
在本發明之一較佳實施例中,該組成物進一步包含至少一靶向媒介,與該至少一磁性奈米粒子之該奈米鑽石合成,用於將該組成物靶向傳遞至在一主體內之一目標位置以進行一高溫治療。
在本發明之一較佳實施例中,在該組成物內的該磁性奈米粒子可供核磁共振造影技術使用以精確地診斷在該目標位置的環境中腫瘤的位置和分布。因此,藉由該核磁共振造影技術可監控通過所述至少一靶向媒介傳遞該組成物之傳遞能力,以判斷該組成物是否到達該主體中的該目標位置並且具有一期望的濃度,以發揮適當的治療效果。
在本發明之一較佳實施例中,該組成物進一步包含至少一醫療媒介,例如抗菌劑,與該至少一磁性奈米粒子之該奈米鑽石合成,其中藉由施加一外部磁場將該組成物適當地引導至集中在一主體內的一目標位置。
在本發明之一較佳實施例中,該離子佈植系統包含:一離子源組件,用於產生離子;一擷取組件,用於從該離子源組件擷取該離子以形成一離子束;一分析磁鐵,用於從該離子束選取該至少一磁性元素;以及一終端,用於承載一工件。該奈米鑽石保持在該工件上,且該工件位在該離子束之一行經路徑上,使得該至少一磁性元素植入到該工件內,進而使得該至少一磁性元素嵌入至該奈米鑽石內。
在本發明之一較佳實施例中,該離子佈植系統包含一電漿離子佈植系統。
本發明還提供一種用於醫療用途之組成物之製備方法,包含:提供一工件,其持有至少一奈米鑽石;將該工件設置在一離子佈植系統中;以及藉由該離子佈植系統將至少一磁性元素嵌入至該至少一奈米鑽石內以形成至少一磁性奈米粒子,進而獲得一組成物。
在本發明之一較佳實施例中,該製備方法進一步包含:將至少一靶向媒介與該至少一磁性奈米粒子之該至少一奈米鑽石合成以獲得該組成物,使得該組成物被靶向傳遞至在一主體內之一目標位置以進行一高溫治療。
在本發明之一較佳實施例中,該製備方法進一步包含:將至少一醫療媒介與該至少一磁性奈米粒子之該至少一奈米鑽石合成以獲得該組成物,並且藉由施加一外部磁場將該組成物適當地引導至集中在一主體內的一目標位置。
在本發明之一較佳實施例中,該至少一醫療媒介包含至少一抗菌劑。
在本發明之一較佳實施例中,藉由該離子佈植系統將至少一磁性元素嵌入至該至少一奈米鑽石內以形成至少一磁性奈米粒子的步驟包含:藉由該離子佈植系統之一離子源組件產生離子;藉由該離子佈植系統之一擷取組件從該離子源組件擷取該離子以形成一離子束;藉由該離子佈植系統之一分析磁鐵從該離子束選取該至少一磁性元素;以及將該至少一磁性元素植入該工件,使得該至少一磁性元素嵌入至該至少一奈米鑽石內。
在本發明之一較佳實施例中,在將該至少一磁性元素植入該工件的步驟後,該製備方法進一步包含:將該工件進行退火。
本發明還提供一種藉由前述之組成物用於製備具以下效果之至少一者的藥物的用途:治療癌症、診斷癌症和治療細菌感染。
10、20、30‧‧‧組成物
100‧‧‧磁性奈米粒子
110‧‧‧奈米鑽石
120‧‧‧磁性元素
130‧‧‧未參雜的奈米鑽石
200‧‧‧靶向媒介
300‧‧‧醫療媒介
400‧‧‧離子佈植系統
410‧‧‧高壓電源供應器
420‧‧‧離子源組件
422‧‧‧電弧腔體
424‧‧‧擷取組件
430‧‧‧分析磁鐵
440‧‧‧終端
450‧‧‧工件
462‧‧‧第一離子束
464‧‧‧第二離子束
500‧‧‧磁性過濾器
600‧‧‧電漿離子佈植系統
610‧‧‧轟擊標靶
為了更清楚地說明本發明實施例或習知技術中的技術方案,下面將對實施例或習知技術描述中所需要使用的所附圖式作一簡單地介紹。下面描述中的所附圖式只是本發明的一些實施例,對於所屬領域的技藝人士而言,在不付出創造性勞動性的前提下,還可以根據這些圖式獲得其他的圖式。
第1A圖顯示根據本發明之第一較佳實施例之組成物的示意圖;第1B圖顯示第1A圖之部分放大視圖;第1C圖顯示將磁性元素植入奈米鑽石內以獲得第1A圖之該組成物之示意圖;第2圖顯示根據本發明之第二較佳實施例之組成物的示意圖;
第3圖顯示根據本發明第三較佳實施例之組成物之示意圖,其中該組成物之磁性奈米粒子進一步與醫療媒介合成;第4圖顯示根據本發明之一較佳實施例之利用一離子佈植系統製備磁性奈米粒子之方法之示意圖;第5A圖和第5B圖分別顯示從第4圖之該離子佈植系統之一工件上獲取奈米粒子之示意圖,以及顯示如何將第5A圖中之奈米粒子分離為磁性奈米粒子與非磁性奈米粒子之示意圖;以及第6圖繪示利用一電漿離子佈植系統製備組成物之方法之示意圖。
請參照附圖中的圖式,其中相同的組件符號代表相同的組件。以下的說明是基於所例示的本發明具體實施例,其不應被視為限制本發明未在此詳述的其它具體實施例。
參照第1A圖,其顯示根據本發明之第一較佳實施例之組成物10的示意圖。第1B圖顯示第1A圖之該組成物10部分放大視圖,以及第1C圖顯示將磁性元素120植入奈米鑽石110內以獲得第1A圖之該組成物10之示意圖。如第1B圖所示,該組成物10包含複數個奈米鑽石110和複數個磁性元素120,其中該磁性元素120選自於由鐵(Fe)、錳(Mn)、鈷(Co)、以及鎳(Ni)元素所組成的群組。並且,如第1B圖和第1C圖所示,該磁性元素120是藉由一離子佈植系統直接植入每一該奈米鑽石110內,使得該複數個磁性元素120被嵌入該奈米鑽石110內以形成一磁性奈米粒子100。
應當注意的是,在本發明中,由於該奈米鑽石110對於人體細胞而言不會展現細胞毒性,且在細胞功能中不會引起明顯地異常,因此
特別有益於將該組成物10應用於生醫和各種醫學應用中,例如藥物傳遞、治療、和診斷技術。然而,本發明的範圍不應只限定在使用該奈米鑽石,任何其他同樣在用於癌症診斷和治療中可展現無明顯毒性和優異的生物相容性之奈米粒子皆可被選用。再者,由於該奈米鑽石110具有較大的表面積對體積比(surface area to volume ratio),故該奈米鑽石110具有較大的承載能力,可用於與各種類型的化合物和/或藥物進行合成,因此可有益於改變和利用該奈米鑽石110的表面功能特性,以針對特定的目的或多種目的用途,將其與治療媒介共軛連接。舉例來說,將局部分佈的藥物傳遞至癌症細胞、限制擴散以增加癌症細胞對藥物的攝取量、提供圖像能力以精確地定位到癌症細胞以及增加藥物保留期以進行癌症治療。此外,相較於正常細胞,由於癌症細胞通常有過度表現的葉酸受體,故可藉由改變該磁性奈米粒子100的表面以形成具有葉酸的改造物(folate moieties)的鏈鍵,進而有效地將該磁性奈米粒子100靶向癌症細胞。因此,由鍵結有葉酸的改造物的該磁性奈米粒子100所靶向的癌症細胞,其在進行高溫治療後,會有較高的死亡率。
參照第2圖,其顯示根據本發明之第二較佳實施例之組成物20的示意圖。該組成物20包含至少一磁性奈米粒子100,其中該磁性奈米粒子100之該奈米鑽石110進一步與靶向媒介200合成。由於該磁性元素120具有鐵磁性,該組成物20適合應用在高溫治療,其中該奈米鑽石110是作為一載具,用於在體內傳遞該磁性元素120至一主體中的一目標位置。該主體包含人類或動物。具體而言,在該主體中進行該高溫治療包含以下步驟:首先,將該組成物20施用至該主體。該磁性奈米粒子100會藉由該靶向媒介200
被引導至接近該目標位置的位置或該目標位置的內部。接著,當該磁性奈米粒子100位在該目標位置之後,該目標位置會被暴露在一電磁場,以從該磁性奈米粒子100產生熱能,使得該目標位置內的溫度上升,進而發揮破壞癌症細胞之功效。此外,在本發明中,由於該組成物20之該磁性奈米粒子100包含該磁性元素120,故該磁性奈米粒子100可供核磁共振造影使用以精確地診斷在病患體內的腫瘤的位置和分布。因此,利用核磁共振造影技術可監控該目標位置的環境和該組成物20通過與該靶向媒介200合成後的傳遞能力,以判斷該組成物20和其所期待的濃度是否被有效地傳送和到達該主體中的該目標位置,以發揮適當的治療效果。在該主體中應用該核磁共振造影技術的方法在所屬領域中為已知的。應當注意的是,由於該組成物20包含該磁性元素120,其在活體內具有優異的核磁共振造影訊號增強能力,因此組成物20也可被用在其他疾病的診斷中。
另一方面,為了確保包含醫療媒介(例如抗菌劑)的施用藥物可被成功地集中在一主體(例如人類)內的正確位置,該藥物可進一步與本發明的該磁性奈米粒子100合成。參照第3圖,其顯示根據本發明第三較佳實施例之組成物30之示意圖。該組成物30包含至少一磁性奈米粒子100,其中該磁性奈米粒子100之該磁性奈米粒子110進一步與醫療媒介300合成。由於該磁性元素120具有鐵磁性,故該組成物30可藉由施加一外部磁場而被輕易地導向期望的位置。因此,該醫療媒介300的傳遞效果可被提升,使得可將藥物(即該組成物30)的總攝取量減少,以防止該醫療媒介300施用所導致之相關聯的副作用。此外,若將該磁性奈米粒子100進一步與抗菌劑合成,該組成物30則適合用在細菌感染的治療。
參照第4圖,其顯示根據本發明之一較佳實施例之利用一離子佈植系統400製備磁性奈米粒子之方法之示意圖。該離子佈植系統400包含一高壓電源供應器410、一離子源組件420、一電弧腔體422、擷取組件424、一分析磁鐵430和一終端440。根據本發明,該磁性奈米粒子的製備方法包含以下步驟:首先,提供一工件450,該工件450上持有奈米鑽石,並且該工件450是被設置在該離子佈植系統400的該終端440上。具體而言,持有奈米鑽石之該工件450的製造方法包含以下步驟:將奈米鑽石粉末溶解在去離子水中以形成一溶液。將該溶液滴在一基板(例如氧化矽晶圓)上。藉由將該基板放置在一燈源底下,以將該基板加熱進而去除該基板上的去離子水,以形成持有該奈米鑽石之該工件450。
當將持有該奈米鑽石之該工件450放置在該終端440之後,將該離子佈植系統400開啟,並且將材料置入該電弧腔體422內,以藉由該離子源組件420產生離子。接著,藉由該擷取組件424從該離子源組件420擷取該離子以形成一第一離子束462,其中該擷取組件424在該離子源組件420和該擷取組件424之間產生電位差,使得該第一離子束462獲得離開該離子源組件420的能量並朝往下游前進。
當將該第一離子束462導向該分析磁鐵430之後,藉由該分析磁鐵430從該第一離子束462中選取期望的磁性元素,因而形成一第二離子束464,其僅包含該磁性元素,並且該第二離子束464被從該分析磁鐵430的位置引導至該終端440。在該終端440上,持有該奈米鑽石之該工件450位在該第二離子束464的行經路徑上。因此,在將該第二離子束464導向該終端440之後,藉由將具有最終控制能量的該第二離子束464植入該工件450,以
將該磁性元素嵌入該奈米鑽石內,進而形成該磁性奈米粒子。
應當注意的是,在進行離子佈值步驟之後,該奈米鑽石之晶格結構可能會被破壞,因此可藉由採用一退火步驟修復該奈米鑽石之晶格結構損傷。具體而言,當將該磁性元素植入該奈米鑽石之後,將該工件450進行退火。並且,藉由進行該退火步驟可成功地修復該奈米鑽石的晶格結構,此功效可藉由採用拉曼(Raman)光譜來檢測進行離子步驟之前、進行離子佈值步驟之後、和進行退火步驟之後的奈米鑽石來證實。舉例來說,根據實驗結果,原始的奈米鑽石可能因為表面石墨結構的影響會在波長1332.5cm-1的位置具有一鑽石峰(diamond peak)以及在波長1579cm-1的位置具有一寬峰(broad peak)。該鑽石峰的半最大值全寬度(full width at half maximum。FWHM)為10.1cm-1。當將鐵離子植入該奈米鑽石後,該鑽石峰會平移至波長1317cm-1的位置,且具有較寬的FWHM(98.5cm-1)。拉曼峰的藍移以及FWHM的加寬都明顯地表示該奈米鑽石的晶格結構受損。再者,在退火之後,該鑽石峰變得較強且會被恢復至原本位在波長1332.4cm-1的位置,且該FWHM也會減少為11.1cm-1。並且,關於表面sp2鍵的其他峰也相應消失。上述結果清楚地表示,鑽石結構被恢復,並且其餘不想要的表面石墨結構或它的化合物被同時消除。
參照第5A圖和第5B圖,其分別顯示從第4圖之該離子佈植系統400之工件450上獲取奈米粒子之示意圖,以及顯示如何將第5A圖中之奈米粒子分離為磁性奈米粒子100與非磁性奈米粒子(即未參雜的奈米鑽石130)之示意圖。如第5A圖所示,在將該磁性元素120嵌入該奈米鑽石110內以形成該磁性奈米粒子100之後,該磁性奈米粒子100與部分未參雜的奈
米鑽石130藉由使用去離子水的超聲波浴一起從該工件450上移除。在本實施例中,由於該奈米鑽石110是以多層的方式堆疊在該基板(例如矽基板)上,因此只有部分的該奈米鑽石110會被植入該磁性元素120。如第5B圖所示,藉由使用一磁性過濾器500可將該磁性奈米粒子100分離出來。該磁性過濾器500可為一細胞分選裝置(magnetic activated cell sorting,MACS® Separator,Miltenyi Biotec Co.)。嵌入有該磁性元素120的該磁性奈米粒子100會被該磁性過濾器500吸引,並且當將奈米鑽石溶液流穿過該磁性過濾器500時,該磁性奈米粒子100會被收集在鄰近的側壁上。該奈米鑽石溶液是藉由將從該工件上250移除的奈米粒子溶解在去離子水中而製備。另外,該未參雜的奈米鑽石130會直接地通過該磁性過濾器500並朝下游前進。接著,被吸引的該磁性奈米粒子100可藉由注入去離子水而排出。最後,獲得該磁性奈米粒子100,並且可將該磁性奈米粒子100收集在承裝有去離子水的燒杯內。
參照第6圖,其繪示利用一電漿離子佈植系統600製備組成物之方法之示意圖。在本實施例中,該電漿離子佈植系統600是用於將磁性元素嵌入奈米鑽石內,其中該奈米鑽石是被放置在該電漿離子佈植系統600之一轟擊標靶610上。
綜上所述,在本發明中,該組成物之該磁性奈米粒子是藉由離子佈值技術將磁性元素植入奈米鑽石內,以用於醫療用途使用。由於該磁性元素是被嵌入不帶有毒性的奈米鑽石內,因此能有效地將疾病治癒的同時也不會使正常的細胞展現毒性。舉例來說,該組成物之該磁性奈米粒子可進一步與靶向媒介合成,使得該組成物可被精確地傳遞至腫瘤細胞以
進行高溫治療。並且,該組成物之該磁性奈米粒子可進一步供核磁共振造影使用,以精確地診斷出在病患體內之腫瘤的位置與分布。因此,利用核磁共振造影可監測組成物通過與靶向媒介合成後用於腫瘤治療的傳遞能力,藉此判斷是否有足夠的磁性奈米粒子到達在病患內的一目標位置以發揮適當的治療效果。此外,該組成物可進一步與其他的醫療媒介合成,例如抗菌劑,使得該組成物可藉由施加一外部磁場而被引導至集中在病患內的一目標位置,以治療細菌感染或者是其他的疾病。
雖然本發明已以較佳實施例揭露如上,但上述較佳實施例並非用以限制本發明,所屬領域中的技藝人士,在不脫離本發明的精神和範圍內,均可作各種更動與潤飾,因此本發明的保護範圍以申請專利範圍中界定的範圍為准。
10‧‧‧組成物
100‧‧‧磁性奈米粒子
110‧‧‧奈米鑽石
120‧‧‧磁性元素
Claims (4)
- 一種組成物,包含:至少一磁性奈米粒子,包括一奈米鑽石和至少一鐵(Fe)元素,其中該至少一鐵元素位在該奈米鑽石內,且該至少一鐵元素是藉由一離子佈植系統嵌入至該奈米鑽石內。
- 一種組成物之製備方法,包含:提供一工件,其持有一奈米鑽石;將該工件設置在一離子佈植系統中;以及藉由該離子佈植系統將至少一鐵(Fe)元素嵌入至該奈米鑽石內以形成一磁性奈米粒子,進而獲得一組成物。
- 如申請專利範圍第2項所述之組成物之製備方法,其中藉由該離子佈植系統將至少一鐵元素嵌入至該奈米鑽石內以形成一磁性奈米粒子的步驟包含:藉由該離子佈植系統之一離子源組件產生離子;藉由該離子佈植系統之一擷取組件從該離子源組件擷取該離子以形成一離子束;藉由該離子佈植系統之一分析磁鐵從該離子束選取該至少一鐵元素;以及將該至少一鐵元素植入該工件,使得該至少一鐵元素嵌入至該奈米鑽石內。
- 如申請專利範圍第3項所述之組成物之製備方法,其中在將該至少一鐵元素植入該工件的步驟後,該製備方法進一步包含:將該工件進行退火。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/180,309 US20170354601A1 (en) | 2016-06-13 | 2016-06-13 | Ion implantation of magnetic elements into nanodiamond particles to form composition for medical usage |
US15/180,309 | 2016-06-13 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201742634A TW201742634A (zh) | 2017-12-16 |
TWI722061B true TWI722061B (zh) | 2021-03-21 |
Family
ID=60573467
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW105139122A TWI722061B (zh) | 2016-06-13 | 2016-11-28 | 磁性元素離子植入奈米鑽石內以形成用於醫療用途之組成物 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20170354601A1 (zh) |
EP (1) | EP3470083A4 (zh) |
JP (1) | JP2019519552A (zh) |
CN (1) | CN107485715A (zh) |
TW (1) | TWI722061B (zh) |
WO (1) | WO2017215309A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10514361B2 (en) * | 2017-08-29 | 2019-12-24 | National Technology & Engineering Solutions Of Sandia, Llc | Tattletale ion-implanted nanoparticles |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4874751B2 (ja) * | 2006-09-27 | 2012-02-15 | 株式会社イオンテクノセンター | Mr画像法に利用する生体標識用ナノダイヤモンド |
US7619228B2 (en) * | 2006-09-29 | 2009-11-17 | Varian Semiconductor Equipment Associates, Inc. | Technique for improved ion beam transport |
CA2766912A1 (en) * | 2009-05-28 | 2010-12-02 | Northwestern University | Nanodiamond particle complexes |
US8193808B2 (en) * | 2009-09-11 | 2012-06-05 | Hewlett-Packard Development Company, L.P. | Optically integrated biosensor based on optically detected magnetic resonance |
JP2011178668A (ja) * | 2010-02-26 | 2011-09-15 | Osaka Univ | Mri造影剤 |
CN102008733A (zh) * | 2010-11-24 | 2011-04-13 | 首都医科大学 | 一种抗肿瘤控释纳米复合物及制备方法 |
TWI588258B (zh) * | 2011-11-17 | 2017-06-21 | 國立交通大學 | 經標記細胞的分離方法及其用途 |
CN103203024B (zh) * | 2013-04-11 | 2014-07-30 | 山西大学 | 一种靶向纳米钻石载体和靶向药物及其制备方法和应用 |
CN104382919A (zh) * | 2014-10-29 | 2015-03-04 | 山西大学 | 一种纳米钻石靶向药物的制备方法和应用 |
-
2016
- 2016-06-13 US US15/180,309 patent/US20170354601A1/en not_active Abandoned
- 2016-11-25 CN CN201611054610.5A patent/CN107485715A/zh active Pending
- 2016-11-28 TW TW105139122A patent/TWI722061B/zh active
-
2017
- 2017-03-27 WO PCT/CN2017/078338 patent/WO2017215309A1/zh unknown
- 2017-03-27 EP EP17812423.6A patent/EP3470083A4/en not_active Withdrawn
- 2017-03-27 JP JP2018566397A patent/JP2019519552A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
TW201742634A (zh) | 2017-12-16 |
EP3470083A4 (en) | 2020-02-19 |
WO2017215309A1 (zh) | 2017-12-21 |
JP2019519552A (ja) | 2019-07-11 |
CN107485715A (zh) | 2017-12-19 |
US20170354601A1 (en) | 2017-12-14 |
EP3470083A1 (en) | 2019-04-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Chao et al. | Iron nanoparticles for low-power local magnetic hyperthermia in combination with immune checkpoint blockade for systemic antitumor therapy | |
Gupta et al. | Manganese-doped magnetic nanoclusters for hyperthermia and photothermal glioblastoma therapy | |
Munaweera et al. | Chemoradiotherapeutic magnetic nanoparticles for targeted treatment of nonsmall cell lung cancer | |
Krukemeyer et al. | Mitoxantrone-iron oxide biodistribution in blood, tumor, spleen, and liver—magnetic nanoparticles in cancer treatment | |
Ribeiro et al. | Nanomaterials in cancer: Reviewing the combination of hyperthermia and triggered chemotherapy | |
US20100106181A1 (en) | In-situ filter | |
JP2009513722A (ja) | 磁性ナノスケール粒子組成物、及びそれに関連した治療方法 | |
KR20100014809A (ko) | 열치료 서셉터 및 이를 사용하는 방법 | |
WO2017193723A1 (zh) | 通过离子植入形成用于中子俘获治疗的组成物 | |
CN114786763A (zh) | 更改交变电场的电阻抗的合成物和方法 | |
Engelmann | Assessing magnetic fluid hyperthermia: magnetic relaxation simulation, modeling of nanoparticle uptake inside pancreatic tumor cells and in vitro efficacy | |
TWI722061B (zh) | 磁性元素離子植入奈米鑽石內以形成用於醫療用途之組成物 | |
WO2016015172A9 (zh) | 一种基于金属富勒烯单晶纳米颗粒特异性阻断肿瘤血管的癌症治疗方法 | |
Ahn et al. | Feasibility study of Fe3O4/TaOx nanoparticles as a radiosensitizer for proton therapy | |
Vukadinović et al. | 90Y-CA/SPIONs for dual magnetic hyperthermia-radionuclide nanobrachytherapy of solid tumours | |
Thong et al. | Multifunctional nanocarriers of Fe3O4@ PLA-PEG/curcumin for MRI, magnetic hyperthermia and drug delivery | |
US20150157872A1 (en) | Device for Treating Cancer by Hyperthermia and the Method Thereof | |
KR20170070978A (ko) | 약물방출 및 열치료 기능을 갖는 스텐트와 이를 이용한 체외 전자기장 구동형 치료 시스템 | |
Zhang et al. | Recent advances in functionalized ferrite nanoparticles: from fundamentals to magnetic hyperthermia cancer therapy | |
Sarkar et al. | A review of nanoferrites: synthesis and application in hyperthermia | |
EP3895734B1 (en) | Iron oxide magnetic particles comprising copper(i)halides | |
Pinank et al. | Revolutionary therapies and manipulation of nanoparticles to cure cancer | |
Li et al. | Magnetic modulation of lysosomes for cancer therapy | |
Engelmann et al. | Magnetic Fluid Hyperthermia in Biomedical Application [M] | |
Shen et al. | NIR and magnetism dual-response multi-core magnetic vortex nanoflowers for boosting magneto-photothermal cancer therapy |