CN105997878B - Reduce the compound micellar carrier medical component of free radical injury - Google Patents

Reduce the compound micellar carrier medical component of free radical injury Download PDF

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CN105997878B
CN105997878B CN201610455627.5A CN201610455627A CN105997878B CN 105997878 B CN105997878 B CN 105997878B CN 201610455627 A CN201610455627 A CN 201610455627A CN 105997878 B CN105997878 B CN 105997878B
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free radical
amifostine
carrier
mentioned
drug
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CN105997878A (en
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陈嘉宏
王朝晖
林炯森
邱铁雄
陈静仪
廖碧虹
苏家琪
廖伟全
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Original Biomedicals Co Ltd
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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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • 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
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K47/02—Inorganic 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers

Abstract

The present invention provides a kind of compound micellar carrier medical component for reducing free radical injury, which includes: at least one metal or its ion；At least one drug or the free radical resisting oxide protected and modified by carrier；And pharmaceutical carrier.Carrier of the invention can be reserved for the activity of drug or polyphenoils, it is made to be not easy to reduce effect by the natural free radical in environment or body fluid, achieve the effect that extend protection, can be applied to mitigate radiation injury and chemotherapeutics side effect.

Description

Reduce the compound micellar carrier medical component of free radical injury
The application is China application No. is 201280054773.7, entitled " to reduce the compound micro- of free radical injury The divisional application of the patent application of born of the same parents' carrier medical component ", the applying date of original application are on November 22nd, 2012.
Technical field
The present invention provides a kind of compound micellar carrier medical component, espespecially a kind of compound micella for reducing free radical injury Carrier medical composition.
Background technique
Amifostine (Amifostine) also known as WR-2721 are the compounds that WR-1065 adds phosphate radical, to protect antioxygen Change active derivative, having obtained multinational pharmaceuticals regulation organ, world core at present can be used as the injury of prevention radiation cure And the indication for the treatment of platinum-based chemotherapy adverse drug (pair) effect.Amifostine can pass through the mode of nature hydrolysis, with life The intracorporal alkaline phosphatase of object (alkaline phosphatase) effect, after the fracture of the bond of its phosphate radical and WR-1065, Ingredient of the WR-1065 as intracellular free radical resisting is discharged, to reduce cytotoxicity.But Amifostine is in the intracorporal distribution half of people The phase declined less than 1 minute, excluding half-life period is 8 minutes, and the Amifostine for only remaining 10% after vein is offerd medicine 6 minutes exists.It is not arranged The Amifostine removed can rapidly be converted into active mercaptan metabolin WR1065 (active free thiol Metabolite), start from acting in vivo.Therefore, clinical use suggests that the vein administering of Amifostine is in radiation cure First three minute is to administer for first 15 minutes in chemotherapy, loses activity to avoid drug.Therefore, most important using Amifostine and Must overcome the problems, such as be half-life period it is too short, and caused by using difficulty.
Past, many researchs were attempted to penetrate different pharmaceutical dosage form or carrier from document, and Amifostine is designed as slowly releasing The mode that non-vein is given is put or can pass through to be administered, although these researchs can extend half-life period or increase Oral Availability, But still can not efficiently control the internal release of Amifostine and the distributed effect of Organic selection is provided, so can not mention It seem the radiation injury etc. prevented when nuclear power plant's radiation leaks for the treatment benefit of clinically more different indications.
Other polyphenoils may also be because of being difficult to save activity, or is easy by body metabolism and when can not provide longer Between free radical resisting protection, so being difficult to apply in prevention radiation injury and reducing the effect of chemotherapeutics ill-effect.
Summary of the invention
In view of in above-mentioned background of invention, in order to meet special demand in industry, the present invention utilizes preceding case (Taiwan case Shen Please Reference Number 101128939) it is a kind of utilize the compound micella technology coating medicine Amifostine of metal ion or other polyphenoils, to answer For reducing radiation injury and chemotherapeutics ill-effect.Compound micella pharmaceutical carrier will reach following purposes, such as extend medicine Object biology Half-life in vivo, changes drug distribution at protection pharmaceutical activity.The compound micella energy of institute's applied metal ion of the present invention Delay the rate of release of drug and change distribution in vivo, achievees the effect that reduce radiation injury and chemotherapeutics side effect.Metal The compound micella of ion can design that different rouge is water-soluble and partial size etc. on demand, to reach specific intracorporeal organ distribution and protection Effect.
The active pharmaceutical ingredient such as Amifostine that compound micella pharmaceutical carrier releases, WR-1065 or other polyphenoils, can The injury for reducing the free radical normal tissue organ that radioactive ray or chemotherapeutic agent generate achievees the effect that reduce toxicity.
The purpose of the present invention is to provide a kind of compound micellar carrier medical component for reducing free radical injury, the composition Object includes: at least one metal or its ion；At least one drug or the polyphenoils protected and modified by carrier；And drug carries Body.
To reach aforementioned invention purpose, above-mentioned metal ion core be selected from one of following group or any combination thereof or Its derivative: iron (Fe), copper (Cu), nickel (Ni), indium (In), calcium (Ca), cobalt (Co), chromium (Cr), gadolinium (Gd), aluminium (Al), tin (Sn), zinc (Zn), tungsten (W), scandium (Sc) and titanium (Ti).
Above-mentioned pharmaceutical carrier is selected from one of following group or any combination thereof or derivatives thereof: polyethylene glycol (poly (ethylene glycol)), poly-aspartic-acid (poly (aspartic acid)), poly- Vetsin (poly (glutamic Acid)), polylysine (poly (lysine)), polyacrylic acid (poly (acrylic acid)), chitosan (chitosan), polyethyleneimine (poly (ethyleneimine)), polymethylacrylic acid (poly (methacrylic Acid)), hyaluronic acid (hyaluronic acid), collagen (collagen), poly- N-isopropylacrylamide (poly (N-isopropyl acrylamide)), amylose (amylose), cellulose (cellulose), poly butyric ester (poly (hydroxybutyrate)), polylactic acid (poly (lactic acid)), poly- succinic acid butyl ester (poly (butylenesuccinate)), polycaprolactone (poly (caprolactone)), carboxymethyl cellulose (carboxymethylcellulose), dextrin (dextran), cyclodextrin (cyclodextrin), polyethylene glycol Vetsin Block copolymer (poly (ethylene glycol)-b-poly (glutamic acid)), Phospholipids (phospholipid).
Above-mentioned pharmaceutical carrier is selected from one of following group or any combination thereof: micro- rouge body (liposome), micella or Macromolecule micella (micelle/polymeric micelle) and dendrimer (dendrimer).
Above-mentioned compound micellar carrier medical component can be bonded with metal or not be bonded, and above-mentioned drug is selected from lower column family One of group or any combination thereof or derivatives thereof: Amifostine (amifostine), WR-1065, vitamin C (ascorbic Acid, Vitamin C) the sweet peptide of, Grains Guang (glutathione), Melatonin (melatonin), tocopherol (tocopherols), tocotrienols (tocotrienols, Vitamin E), L-carnitine (L-carnitine), carrot Element (carotenes), reduced form ubiquinone (ubiquinol), lipoic acid (lipoic acid), polyphenol (polyphenols), youngster Tea phenol amine (catecholamine), curcumin (curcumin), resveratrol (resveratrol), polydatin (piceid), acetylcysteine (acetylcysteine), tetramethyl croak pyridine oxide (Tempo), asarone (asarone), aminoguanidine (aminoguanidine), vitamin E monoglycosides (tocopherol monoglucoside), Radix Glycyrrhizae Acid (glycyrrhizic acid), epicatechin (epicatechin), flavonoids (flavonoid), orientin (Orientin), Wei Caining (vicenin), 2- mercapto radical propionyl group-glycine (MPG (2-mercaptopropionyl )) and mesna (Mesna (2-mercaptoethanesulfonic acid)) glycine.
One kind is for reducing the compound micellar carrier medical component of free radical injury, which includes: iron ion；Ammonia Phosphorus spit of fland；And pharmaceutical carrier, the carrier are polyethylene glycol Vetsin block copolymer.
To reach aforementioned invention purpose, the drug can restore the biomolecule aoxidized, as reducing agent with extensive Its multiple function；Free radical can be prevented persistently to transmit and attack according to its antioxidant effect；Radiation, ultraviolet light, chemotherapeutic can be reduced Free radical caused by product, Electromagnetic Environmental Effect etc. achievees the effect that protect free radical injury and reduces its toxicity.
Detailed description of the invention
In conjunction with attached drawing the following detailed description, when reading, be will be more readily understood by the general introduction of front and the present invention.So And, it should be understood that the preferred embodiment the invention is not limited to shown in.
Fig. 1: the compound micella pharmaceutical carrier with metallic core for showing the formation of embodiment according to the present invention one shows It is intended to.
Fig. 2: showing Comet Assay (Comet Assay) striograph, there is CON (negative sense control group), UV (forward direction control respectively Processed group), API 40X (2 hours), API 40X (30 minutes), FeP 40X (2 hours), FePA 20X (2 hours), FePA 20X (30 minutes).
Fig. 3: showing Comet Assay (Comet Assay) DNA hangover rate (%) datagram, there is CON (negative sense control respectively Group), UV (positive control group), API 40X (2 hours), API 40X (30 minutes), FeP 40X (2 hours), (2 is small by FePA 20X When), FePA 20X (30 minutes).P < 0.001 * * compared to UV group have significant difference,#P < 0.05 is compared to API 40X 2 hours groups have significant difference,▲▲▲P < 0.001 has significant difference compared to 2 hours groups of FePA 20X.
Specific embodiment
The present invention is demonstrated with the following examples and is illustrated, but the present invention is not limited by following embodiments.
Embodiment one
The compound micella pharmaceutical carrier controlled release form of metallic core is prepared
Fig. 1 is the compound micella pharmaceutical carrier schematic diagram with metallic core.Center is metal or metal ion 120；In It is polyphenoils or other similar drug 110 by heart metal or metal ion；It is peripheral then be carrier 100.
Active material
Amifostine is polyphenoils, is derivative of the WR-1065 plus phosphate radical protection antioxidant activity, the world is more Traditional Chinese medical science drug act organ core can be used as the indication of the injury of prevention radiation cure and platinum-based chemotherapy drug side effect.
Compound micella pharmaceutical carrier
Raw material is provided, which includes that 15g γ-benzyl-L-glutamate, 7.5gtriphosgene are dissolved in 150mL Anhydrous tetrahydrofuran (THF) is stirred to react in lower 55 DEG C of nitrogen environment to clear solution, is deposited in 400mL after concentration N-hexane is recrystallized with 300mL n-hexane/ethyl acetate (1/1) after removing n-hexane, list can be obtained after filtering Body N-carboxy- γ-benzyl-L-glutamate anhydride (BLG-NCA)；15g BLG-NCA and 2.1g α- Amino- ω-methoxy-poly (ethylene glycol) (PEG-NH2) is dissolved in 43mL dimethyl sulfoxide (DMSO), it is stirred to react 72 hours for 40 DEG C, crude product is deposited in 215mL diethyl ether after the completion, removes diethyl 315mL ethanol is added after ether and 25 DEG C of 210mL 1N NaOH is stirred to react 24 hours, then with 35%HCl ice bath PH value is adjusted to 7.0, using 3500 dialysis membrane dialysis purification of MWCO, polyethylene glycol Vetsin block can be obtained after freeze-drying Copolymer (PEG-b-PGA).
Raw material is provided, which includes 206.44mg Amifostine, 825.50mg polyethylene glycol Vetsin block copolymer (PEG-b-PGA) with 206.44mg frerrous chloride (FeCl24H2O)；The raw material is placed in 41.288ml buffer HEPES [4- (2-hydroxyethyl) -1-piperazinee-thanesulfonic acid)] in, at 25 DEG C, pH value 7.0, revolving speed 200rpm carries out even dynamic program of interfering with or disturb each other.
Composite FePA allotment ratio PEG-b-PGA:FeCl24H2O:amifostine=4:1:1 (w:w:w, with Weight is as ratio), preferable Amifostine reaction density: 5mg/mL.Whereby, the Amifostine is via the ferrous ion (Fe2+) and should Polyethylene glycol Vetsin block copolymer (PEG-b-PGA) directly carries out self assembly (self-assembly) by coordinate bond Reaction.
Formulation Example 1 (FePA)
Antioxidant effect-in vitro test of the compound micella pharmaceutical carrier of metallic core
This experiment is simulated using UV irradiating cell by being influenced caused by radiating, and with comet test (Comet Assay) as detection method.Comet test is a kind of method of quick, sensitive, easy inspection DNA damage, is widely applied In DNA radiation insult, the detection of DNA crosslinking, the genetoxic assessment of drug, the work such as apoptosis identification.
Experiment is divided into seven groups, wherein
API is Amifostine 1mg/mL；
FePA ingredient is frerrous chloride 1mg/mL, PEG-b-PGA 4mg/mL, Amifostine 1mg/mL；
FeP ingredient is frerrous chloride 1mg/mL and PEG-b-PGA 4mg/mL；
1mL is respectively bestowed in each experimental group.Processing mode is as shown in following table one:
Table one
Title Disk number Condition processing
CON 2 It does not handle completely, does not irradiate UV
UV 2 Directly shine UV
API 40x 2 According to dosing in 30 minutes before UV
FePA 20x 2 According to dosing in 30 minutes before UV
API 40x 2 According to dosing in two hours before UV
FeP 40x 2 According to dosing in two hours before UV
FePA 20x 2 According to dosing in two hours before UV
CON: negative sense control group (Negative Control)
UV: positive control group (Positive Control)
As forward direction controls
40X:40 times dilutes
20X:20 times dilutes
By mice embryonic liver cell (BNLCL.2) with 3*105The density of cell/mL is inoculated in 35mm culture dish, and is trained It is tested again after supporting at least 20 hours.Supernatant is removed, control group and experimental group compound is added according to time order and function individually Concentration mixes the fresh medium containing serum.It is slightly cleaned using PBS, culture dish is allowed to irradiate UVB (100Jm-2UVB Doses) after UV, 2mL fresh medium is added, then at incubator (incubator) (37 DEG C/4%CO of temperature2) carry out culture 4 Hour.To drug effect, with glue stick gently by under cell scraper, metastatic cells liquid calculates total cell number, then into centrifuge tube It carries out centrifugation (1200rpm, 5 minutes), with PBS (Ca2+, Mg2+Free) cleaning is primary, and PBS, which is added, makes its cell number 1* 105cell/mL。
Low melting point agar glue bottle cap is turned into pine and is placed in 95 DEG C of boiled water water proof heating and melting after five minutes, then is placed in 37 DEG C of water It is cooled down within domain slot at least 20 minutes.The combination cell (1 × 10 at 37 DEG C5/ ml) with melting low melting point agar glue with 7 μ L: 70 μ L are mixed, and draw 60 μ L to CometSlide after mixing and immediatelyTM.Slide (slides) is laid flat and is protected from light and is placed in ice Upper 10 minute.After slide to be immersed in the lysate (lysis solution) of pre-cooling, it is placed in 4 DEG C of refrigerators 30 minutes.Gently After striking buffer extra on slide (buffer), slide is soaked in the fresh alkaline uncoiling solution (Alkaline to purchase Unwinding Solution) after, at room temperature, it is protected from light 60 minutes.The alkaline electrophoresis that 950mL pre-cooling is added on electrophoresis tank is molten Liquid (Alkaline Electrophoresis Solution), then slide is put, slide Tray Overlay is covered, is run Adhesive tape part is 21V, 30 points.Electrophoresis liquid is lightly excluded, is then soaked in deionized water 2 times, every time 5 minutes.It is soaked in 70% Ethyl alcohol 5 minutes.The drying sample 15 minutes in exhaust gas cabinet (hood), drying can make cell that single plane be presented, convenient for observing, Sample can be put under desiccant in this stage and store at room temperature.SYBR Green I after 100 μ L dilution is added on dry Colloid is being put in 4 DEG C of refrigerators 5 minutes.It gently pats and removes extra SYBR solution, and be protected from light slide, dry at room temperature Afterwards, through luminescence microscope (fluorescence microscopy) carry out filming image (I maximum excitation Light and scattering light are respectively 494nm/521nm. and adjust fluorescent filter to enough light sources) 200X.
Experimental result such as Fig. 2, Fig. 3 are it is found that give FePA20X, API in 30 minutes or first 2 hours before either irradiation UV 40X, FeP 40X, compared to positive control group (UV), the % average value that trails all is significantly reduced, and with normally without irradiation UV Control group (CON) indifference, it can thus be appreciated that the damage for truly having obvious protection cell caused from UV irradiation of FePA is given, and Its state almost with normally without irradiation the cell of UV it is identical.
The experimental result that other living body radiation injuries or chemotherapy ill-effect improve
Efficacy results (Efficacy Result)
In animal experiment, the test of mouse NMRI (every 20-30 grams) 30 days acute radiation protections, radiation control group: In the radioactive ray for receiving 1,4,8 dagger-axe thunder (Gy) dosage in 10 minutes；Standard care group: receive the drug ammonia phosphorus of FDA license listing Receive the radiation of 8Gy dosage after the intravenous injection of spit of fland (6.25mg/kg) in 30 minutes, 10 minutes.A-01 is FePA, allotment ratio PEG-b-PGA:FeCl2·4H2O:amifostine=4:1:1 (w:w:w).A-01 experimental group: receive A-01 trial drug Receive in 120 minutes, 10 minutes after 37.5mg/kg (having identical Amifostine medicament contg with standard care group) intravenous injection The radiation of 8Gy dosage.Observe white blood cell the 30th day number and survival rate analysis.
Experimental result is as shown in following table two, and white blood cell count is up to the 3-4 times of simple control for receiving radiation in A-01 experimental group Processed group, obvious drug A-01 has at least two hours or more hemopoietic system protections, can be effectively reduced radiation cause vulnerable to The ill-effect of infection.And in this test, Amifostine is 6.25mg/kg in the A-01 drug with mouse of offeing medicine, and is scaled The dosage that the human body of 60kg is about 30mg has protection, and (the A01 drug micellar carrier containing PEG-b-PGA etc. is total 180mg), can prevent dosage when incidence cancer patient receives Amifostine treatment through U.S. FDA core compared to original Amifostine is 200mg/m2, and be only capable of being administered in or so first three minute of radiation cure, and only glandula protection has significant difference, conversion It is 320mg (200mg/m that 60kg adult, which about needs Amifostine drug,2), it is seen that the drug of A-01 can with throughout curve accumulate with Slow release reaches superior anti-radiation curative effect.
Table two
(- the indicate experiment is because of dose radiation is not enough to generate serious hemopoietic system injury therefore does not administer drug；
-- group is not because the rats and mice safety testing in other acute toxicities occurs any side effect, in normal range (NR) Therefore white blood cell number is not presented.)
In conclusion provided by this case it is a kind of using the compound micella technology coating medicine Amifostine of metal ion or other The method of polyphenoils really belongs to innovation to be applied to reduce radiation injury and chemotherapeutics side effect, in past known techniques simultaneously No effective mode removes the drug release of control Amifostine, and provides intracorporeal organ selective distribution.Above-mentioned multinomial effect is real Category fully complies with novel and progressive Statutory Invention patent requirement, and whence is filed an application in accordance with the law, earnestly asks that your office checks and approves this part hair Bright patent application case, to encourage invention.

Claims (4)

1. the purposes that a kind of compound micellar carrier medical component reduces the drug of free radical injury as preparation, it is characterised in that The compound micellar carrier medical component includes:
One ferrous ion；
One Amifostine, wherein above-mentioned Amifostine is that coordination is bonded to above-mentioned ferrous ion；And
One pharmaceutical carrier, which is polyethylene glycol Vetsin block copolymer, wherein above-mentioned pharmaceutical carrier is to match Position is bonded to above-mentioned ferrous ion；
Wherein above-mentioned Amifostine can be accumulated with throughout curve and achieve the effect that reduce free radical injury with slow release.
2. the use that compound micellar carrier medical component as described in claim 1 reduces the drug of free radical injury as preparation On the way, it is characterised in that wherein the Amifostine can prevent free radical from persistently transmitting and attack according to its antioxidant effect.
3. the use that compound micellar carrier medical component as described in claim 1 reduces the drug of free radical injury as preparation On the way, it is characterised in that wherein the Amifostine can reduce free radical caused by radiation, ultraviolet light, chemotherapeutic drugs, reach protection Free radical injury and the effect for reducing its toxicity.
4. the purposes that a kind of compound micellar carrier medical component reduces the drug of free radical injury as preparation, it is characterised in that The constituent includes:
Iron ion；Amifostine；And pharmaceutical carrier, the carrier are polyethylene glycol Vetsin block copolymer；
Wherein above-mentioned Amifostine is that coordination is bonded to above-mentioned iron ion, wherein above-mentioned pharmaceutical carrier is that coordination is bonded to The iron ion stated；
Wherein above-mentioned Amifostine can be accumulated with throughout curve and achieve the effect that reduce free radical injury with slow release.
CN201610455627.5A 2012-11-22 2012-11-22 Reduce the compound micellar carrier medical component of free radical injury Active CN105997878B (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1890295A (en) * 2003-12-10 2007-01-03 株式会社东京大学Tlo Coordination complex of diaminocyclohexaneplatinum(II) with block copolymer containing poly(carboxylic acid) segment and antitumor agent comprising the same

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120197060A1 (en) * 2009-06-18 2012-08-02 University Of Utah Research Foundation Radiation enhanced macromolecular delivery of therapeutic agents for chemotherapy technology
JP2011105792A (en) * 2009-11-12 2011-06-02 Japan Science & Technology Agency Block copolymer, block copolymer-metal complex composite material, and hollow structure carrier using the same
HUE027711T2 (en) * 2010-03-26 2016-11-28 Onconova Therapeutics Inc Improved stable aqueous formulation of (e)-4-carboxystyryl-4-chlorobenzyl sulfone
WO2012058552A1 (en) * 2010-10-29 2012-05-03 Intezyne Technologies, Incorporated Iron stabilized polymer micelles for drug delivery applications

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1890295A (en) * 2003-12-10 2007-01-03 株式会社东京大学Tlo Coordination complex of diaminocyclohexaneplatinum(II) with block copolymer containing poly(carboxylic acid) segment and antitumor agent comprising the same

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Micelles Based on Biodegradable Poly(L-glutamic acid)-b-Polylactide with Paramagnetic Gd Ions Chelated to the Shell Layer as a Potential Nanoscale MRI-Visible Delivery System;Zhang Guodong et al.;《Biomacromolecules》;20071130;第9卷(第1期);36-42 *
Preparation of amifostine polylactide-co-glycolide microspheres and its irradiation protective to mouse through oral administration;Lu et al.;《Drug Development and Industrial Pharmacy》;20111231;第37卷(第12期);1473-1480 *
Superparamagnetic iron oxide nanoparticles：magnetic nanoplatforms as drug carriers;Wahajuddin，Sumit Arora.;《International Journal of Nanomedicine》;20120705;第7卷;3445-3471 *

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