CN105997878A - Composite micelle carrier pharmaceutical composition capable of reducing damage caused by free radicals - Google Patents
Composite micelle carrier pharmaceutical composition capable of reducing damage caused by free radicals Download PDFInfo
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- CN105997878A CN105997878A CN201610455627.5A CN201610455627A CN105997878A CN 105997878 A CN105997878 A CN 105997878A CN 201610455627 A CN201610455627 A CN 201610455627A CN 105997878 A CN105997878 A CN 105997878A
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- A61K9/127—Liposomes
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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Abstract
The invention provides composite micelle carrier pharmaceutical composition capable of reducing damage caused by free radicals. The composition comprises at least one type of metal or an ion of the metal, at least one drug or carrier protected or modified free-radical-resistant oxide and a drug carrier. The carrier can reserve activity of the drug or the antioxidant, so that the efficacy of the drug or the antioxidant is not easily reduced by natural free radicals in the environment or body fluid, the lasting time of the protective efficacy is prolonged, and the composition can be used for relieving radiation injury and side effects of chemotherapy drugs.
Description
The application is China's Application No. 201280054773.7, invention entitled " reduction free radical wound
The compound micellar carrier medical component of evil " the divisional application of patent application, the applying date of original application
It it is on November 22nd, 2012.
Technical field
The present invention provides a kind of compound micellar carrier medical component, espespecially a kind of reduction free radical injury
Compound micellar carrier medical composition.
Background technology
Amifostine (Amifostine), has another name called WR-2721, is the WR-1065 compound that adds phosphate radical,
For protecting the derivant of antioxidant activity, having obtained multinational pharmaceuticals regulation office of world core can
The indication acted on as injury and treatment platinum-based chemotherapy adverse drug (secondary) of prevention radiation cure.
Amifostine can pass through the mode of nature hydrolysis, with the alkali phosphatase (alkaline in organism
Phosphatase) effect, after the bond of its phosphate radical with WR-1065 being ruptured, discharges WR-1065
As the composition of intracellular free radical resisting, to reduce cytotoxicity.But amifostine in human body point
The cloth half-life is less than 1 minute, and the eliminating half-life is 8 minutes, only remains 10% after vein is offerd medicine 6 minutes
Amifostine exist.The amifostine not being excluded can be converted into active mercaptan metabolite rapidly
WR1065 (active free thiol metabolite), and start from internal effect.Therefore, face
It is first three minute that bed uses the vein of suggestion amifostine to cast at radiation cure, is front in chemotherapy
Within 15 minutes, cast, to avoid medicine to lose activity.Therefore, use amifostine most important and must overcome
Problem is i.e. that the half-life is too short, and the use difficulty caused.
Past much research is attempted from document, through different pharmaceutical dosage forms or carrier, being set by amifostine
It is calculated as slowly discharging or can pass through the mode that non-vein gives to be administered, although these researchs can extend partly
Decline phase or increase Oral Availability, but still cannot efficiently control the internal release of amifostine with
And provide the selective distributed effect of organ, so controlling of the most more different indication cannot be provided
Curative effect benefit, seems that prevention nuclear power plant radiates the radiation injury etc. when leaking.
Other polyphenoils are likely to because being difficult to preserve activity, or easily cannot by body metabolism
There is provided the free radical resisting protection of long period, so being difficult to apply in prevention radiation injury and reductionization
Treat the effect of adverse drug effect.
Summary of the invention
In view of in above-mentioned background of invention, in order to meet special demand in industry, before the present invention utilizes
Case (Taiwan case Application No. 101128939) one utilizes metal ion to be combined micella technology coating medicine
Amifostine or other polyphenoils, to be applied to reduce radiation injury and chemotherapeutics ill effect.Multiple
Close micella pharmaceutical carrier and will reach following purpose, as extended medicine biology Half-life in vivo, protection medicine
Thing activity, change drug distribution.Institute of the present invention applied metal ion is combined micella and can delay medicine
Rate of release and change distribution in vivo, reduce the effect of radiation injury and chemotherapeutics side effect.
Metal ion is combined micella can design different fat water solublity and particle diameter etc., on demand to reach particular volume
The distribution of interior organ and the effect of protection.
Active constituents of medicine such as the amifostine that compound micella pharmaceutical carrier discharges, WR-1065 or other are anti-
Oxide, can reduce the wound of the radical pair normal structure organ of lonizing radiation or chemotherapeutic agent generation
Evil, reduces the effect of toxicity.
The purpose of the present invention is i.e. providing a kind of compound micellar carrier medicine composition reducing free radical injury
Thing, this constituent comprises: at least one metal or its ion；At least one medicine or protected by carrier
And the polyphenoils modified；And pharmaceutical carrier.
For reaching aforementioned invention purpose, above-mentioned metal ion core selected from one of following group or its
Combination in any or derivatives thereof: ferrum (Fe), copper (Cu), nickel (Ni), indium (In), calcium (Ca), cobalt (Co),
Chromium (Cr), gadolinium (Gd), aluminum (Al), stannum (Sn), zinc (Zn), tungsten (W), scandium (Sc) and titanium (Ti).
Above-mentioned pharmaceutical carrier is selected from one of following group or its combination in any or derivatives thereof: poly-second
Glycol (poly (ethylene glycol)), poly-aspartic-acid (poly (aspartic acid)),
Poly-glutamic acid (poly (glutamic acid)), polylysine (poly (lysine)), polyacrylic acid
(poly (acrylic acid)), spherical chitosan (chitosan), polymine
(poly (ethyleneimine)), polymethylacrylic acid (poly (methacrylic acid)), thoroughly
Bright matter acid (hyaluronic acid), collagen protein (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)), poly-oneself
Lactone (poly (caprolactone)), carboxymethyl cellulose (carboxymethylcellulose),
Dextrin (dextran), cyclodextrin (cyclodextrin), polyethylene glycol glutamic acid block copolymer
(poly (ethylene glycol)-b-poly (glutamic acid)), phospholipid
(phospholipid)。
Above-mentioned pharmaceutical carrier is selected from one of following group or its combination in any: micro-fat body
(liposome), micella or macromolecule micella (micelle/polymeric micelle) and dendroid are high
Molecule (dendrimer).
Above-mentioned compound micellar carrier medical component can be with metal bond or non-bond, above-mentioned medicine
Selected from one of following group or its combination in any or derivatives thereof: amifostine (amifostine),
WR-1065, vitamin C (ascorbic acid, Vitamin C), the sweet peptide of Guang (glutathione),
Melatonin (melatonin), tocopherol (tocopherols), tocotrienols (tocotrienols,
Vitamin E), L-carnitine (L-carnitine), carotene (carotenes), reduced form
Ubiquinone (ubiquinol), thioctic acid (lipoic acid), polyphenol (polyphenols), catecholamine
(catecholamine), curcumin (curcumin), resveratrol (resveratrol), white hellebore
Alcohol glycosides (piceid), acetylcysteine (acetylcysteine), tetramethyl croak pyridine oxide
(Tempo), asarone (asarone), aminoguanidine (aminoguanidine), vitamin E monosaccharide
Glycosides (tocopherol monoglucoside), glycyrrhizic acid (glycyrrhizic acid), epicatechin
(epicatechin), flavonoid (flavonoid), orientin (Orientin), Wei Caining (vicenin),
2-mercapto radical propionyl group-glycine (MPG (2-mercaptopropionyl glycine)) and mesna
(Mesna(2-mercaptoethanesulfonic acid))。
One is used for reducing the compound micellar carrier medical component of free radical injury, and this constituent comprises:
Iron ion；Amifostine；And pharmaceutical carrier, this carrier is polyethylene glycol glutamic acid block copolymer.
For reaching aforementioned invention purpose, described medicine can be as reducing agent, the life that reduction is aoxidized
Thing molecule, to recover its function；Free radical can be stoped persistently to transmit and attack according to its antioxidant effect；
The free radical that radiation, ultraviolet, chemotherapeutic drugs, Electromagnetic Environmental Effect etc. are caused can be reduced, reach
Protection free radical injury and the effect reducing its toxicity.
Accompanying drawing explanation
General introduction above, and the present invention combining accompanying drawing the following detailed description, will more hold during reading
Change places understanding.It will be appreciated, however, that the invention is not limited in shown preferred embodiment.
Fig. 1: show, according to what embodiments of the invention one were formed, there is answering of metallic core
Close micella pharmaceutical carrier schematic diagram.
Fig. 2: show Comet Assay (Comet Assay) striograph, have respectively CON (negative sense control group),
UV (forward control group), API 40X (2 hours), API 40X (30 minutes), FeP 40X (2 hours),
FePA 20X (2 hours), FePA 20X (30 minutes).
Fig. 3: show Comet Assay (Comet Assay) DNA hangover rate (%) datagram, have respectively
CON (negative sense control group), UV (forward control group), API 40X (2 hours), API 40X (30 minutes),
FeP 40X (2 hours), FePA 20X (2 hours), FePA 20X (30 minutes).* * P < 0.001 phase
Compared with UV group have significant difference,#P < 0.05 has significant difference compared to 2 hours groups of API 40X
Different,▲▲▲P < 0.001 has significant difference compared to 2 hours groups of FePA 20X.
Detailed description of the invention
The present invention gives demonstration with the following examples and illustrates, but the present invention is not limited by following embodiment
System.
Embodiment one
Metallic core is combined the preparation of micella pharmaceutical carrier controlled release form
Fig. 1 is the compound micella pharmaceutical carrier schematic diagram with metallic core.Center is metal or metal
Ion 120；Central metal or metal ion side are polyphenoils or other similar medicines 110；Periphery is then
For carrier 100.
Active substance
Amifostine is polyphenoils, is that WR-1065 adds that phosphate radical protects the derivant of antioxidant activity,
The multinational pharmaceuticals in world regulation office core can be as prevention radiation cure injury and platinum-based chemotherapy
The indication of medicine side effect.
Compound micella pharmaceutical carrier
Thering is provided raw material, this raw material comprises 15g γ-benzyl-L-glutamate, 7.5g
Triphosgene is dissolved in the anhydrous tetrahydrofuran of 150mL (THF) in nitrogen environment lower 55 DEG C
Stirring reaction is to settled solution, and concentration postprecipitation is in 400mL n-hexane, after removing n-hexane
With 300mL n-hexane/ethyl acetate (1/1) recrystallization, monomer after filtration, can be obtained
N-carboxy-γ-benzyl-L-glutamate anhydride(BLG-NCA)；15g BLG-NCA
It is dissolved in 2.1g α-amino-ω-methoxy-poly (ethylene glycol) (PEG-NH2)
43mL dimethyl sulfoxide (DMSO), 40 DEG C of stirrings are reacted 72 hours, slightly produce after completing
Thing is deposited in 215mL diethyl ether, adds 315mL ethanol after removing diethyl ether
With 210mL 1N NaOH 25 DEG C stirring reaction 24 hours, then adjust pH value with 35%HCl ice bath
To 7.0, utilize MWCO 3500 dialyzer dialysis purification, polyethylene glycol bran after lyophilization, can be obtained
Amino acid block copolymer (PEG-b-PGA).
Thering is provided raw material, this raw material comprises 206.44mg amifostine, 825.50mg polyethylene glycol bran
Amino acid block copolymer (PEG-b-PGA) and 206.44mg ferrous chloride (FeCl2 4H2O)；Should
41.288ml buffer HEPES [4-(2-hydroxyethyl)-1-piperazinee inserted by raw material
-thanesulfonic acid)] in, with at 25 DEG C, pH value be 7.0, rotating speed 200rpm carries out
Even dynamic program of interfering with or disturb each other.
The allotment ratio PEG-b-PGA:FeCl2 4H2O:amifostine=4 of composite FePA:
1:1 (w:w:w, using weight as ratio), preferable amifostine reaction density: 5mg/mL.Thereby,
This amifostine is via this ferrous ion (Fe2+) and this polyethylene glycol glutamic acid block copolymer
(PEG-b-PGA) self assembly (self-assembly) reaction is directly carried out by coordinate bond.
Formulation Example 1 (FePA)
Metallic core is combined the antioxidant effect-in vitro tests of micella pharmaceutical carrier
This experiment utilizes the simulation of UV irradiating cell to be affected by radiating to be caused, and with comet test
(Comet Assay) is as detection method.Comet test is a kind of quick, sensitive, easy inspection
The method of DNA damage, is widely used in DNA radiation injury, the detection of DNA crosslinking, the something lost of medicine
Pass toxicity evaluation, the work such as apoptosis qualification.
Experiment is divided into into seven groups, wherein
API is amifostine 1mg/mL；
FePA composition is ferrous chloride 1mg/mL, PEG-b-PGA 4mg/mL, amifostine
1mg/mL；
FeP composition is ferrous chloride 1mg/mL and PEG-b-PGA 4mg/mL；
Respectively bestow 1mL in each experimental group.Processing mode is as shown in following table one:
Table one
| Title | Dish number | Condition processes |
| CON | 2 | Do not process, do not irradiate UV |
| UV | 2 | Directly according to UV |
| API 40x | 2 | According to UV dosing in first 30 minutes |
| FePA 20x | 2 | According to UV dosing in first 30 minutes |
| API 40x | 2 | According to dosing in before UV two hours |
| FeP 40x | 2 | According to dosing in before UV two hours |
| FePA 20x | 2 | According to dosing in before UV two hours |
CON: negative sense control group (Negative Control)
UV: forward control group (Positive Control)
Such as forward control
40X:40 times dilutes
20X:20 times dilutes
By mice embryonic hepatocyte (BNLCL.2) with 3*105The density of cell/mL is inoculated in 35mm training
Support in ware, and test again after cultivating at least 20 hours.Remove supernatant, individually according to the time first
Rear addition control group and the experimental group compound concentration mixing fresh medium containing serum.Use PBS a little
Clean, after allowing culture dish irradiate UVB (100J m-2UVB doses) UV, add the fresh training of 2mL
Nutrient solution, then at incubator (incubator) (37 DEG C/4%CO of temperature2) carry out cultivating 4 hours.Treat
Medicine effect, with glue stick being scraped by cell gently, in transfer Cell sap to centrifuge tube, calculates total thin
Born of the same parents' number, is then centrifuged precipitation (1200rpm, 5 minutes), with PBS (Ca2+, Mg2+Free) clear
Wash once, add PBS and make its cell number be 1*105cell/mL。
Low melting point Eucheuma gelatinosum glue bottle cap is turned pine and is placed in 95 DEG C of boiled water water proof heating and melting after 5 minutes, then
It is placed in 37 DEG C of waters grooves to cool down at least 20 minutes.Cell (1 × 10 is combined at 37 DEG C5/ ml) with
Melted low melting point Eucheuma gelatinosum glue mixes with 7 μ L:70 μ L, after mixing and draws 60 μ L immediately
To CometSlideTM.Slide (slides) is kept flat and lucifuge is placed in 10 minutes on ice.Slide is soaked
Bubble, after the lysate (lysis solution) of pre-cooling, is placed in 4 DEG C of refrigerators 30 minutes.Rap
After buffer (buffer) unnecessary on slide, slide is soaked in the fresh alkaline uncoiling purchased molten
After liquid (Alkaline Unwinding Solution), at room temperature, lucifuge 60 minutes.At electrophoresis tank
Alkaline electrophoresis solution (the Alkaline Electrophoresis of upper addition 950mL pre-cooling
Solution), then slide is put, covers slide Tray Overlay, run adhesive tape part be 21V,
30 points.Get rid of electrophoresis liquid lightly, be then soaked in deionized water 2 times, each 5 minutes.It is soaked in
70% ethanol 5 minutes.Drying sample 15 minutes in exhaust gas cabinet (hood), dry meeting makes cell present list
The plane of one, it is simple to observing, sample can be put under desiccant in this stage and store at room temperature.By 100
SYBR Green I after μ L dilution is added on dry colloid, is being put in 4 DEG C of refrigerators 5 minutes.Gently
Pat and remove unnecessary SYBR solution, and make slide lucifuge, after drying at room temperature, show through fluorescent
Micro mirror (fluorescence microscopy) carry out filming image (I maximum excitation light
It is respectively 494nm/521nm. with scattered light and adjusts fluorescent filter to enough light sources) 200X.
Experimental result such as Fig. 2, Fig. 3 understand, and either irradiate first 30 minutes of UV or front 2 little
Time give FePA20X, API 40X, FeP 40X, compared to forward control group (UV), its
Hangover % meansigma methods all significantly reduces, and with normal without irradiating UV control group (CON) indifference
It is different, it can thus be appreciated that the substantially protection cell that truly has giving FePA avoids what UV irradiation was caused
Damage, and its state is almost identical with the normal cell without irradiating UV.
The experimental result that other live body radiation injuries or chemotherapy ill effect improve
Efficacy results (Efficacy Result)
In animal experiment, mice NMRI (every 20-30 gram) the acute radiation protection of 30 days is tested,
Radiation control group: accepted the lonizing radiation of 1,4,8 dagger-axe thunder (Gy) dosage in 10 minutes；Standard care group:
Accept FDA license listing medicine amifostine (6.25mg/kg) intravenous injection after 30 minutes, in 10 minutes
Accept the radiation of 8Gy dosage.A-01 is FePA, allocates ratio PEG-b-PGA:FeCl2·4H2O:
Amifostine=4:1:1 (w:w:w).A-01 experimental group: accept A-01 trial drug
After 37.5mg/kg (having identical amifostine medicament contg with standard care group) intravenous injection 120 minutes,
The radiation of 8Gy dosage is accepted in 10 minutes.Observe leukocyte the 30th day number and survival rate analysis.
Experimental result is as shown in following table two, and in A-01 experimental group, white blood cell count is simple up to 3-4 times accepts
The control group of radiation, obvious medicine A-01 has the hemopoietic system protection of more than at least two hours,
Can effectively reduce radiation and cause the ill effect of susceptible.And in this test, offer medicine with mice
A-01 medicine in amifostine be 6.25mg/kg, the human body being scaled 60kg is about the dosage of 30mg
I.e. there is protection (180mg altogether such as the A01 medicine micellar carrier containing PEG-b-PGA etc.), compare original ammonia phosphorus
It is 200mg/m that spit of fland can prevent incidence cancer patient to accept dosage when amifostine is treated through U.S. FDA core2,
And be only capable of in about first three minute of radiation cure being administered, and only glandula protection has significant difference,
It is 320mg (200mg/m that conversion 60kg adult about needs amifostine medicine2), it is seen that the medicine of A-01 is permissible
Throughout curve accumulation and slowly release reach more excellent radioprotective curative effect.
Table two
This experiment of (-represent is because dose radiation is not enough to produce the injury of serious hemopoietic system therefore does not casts
Medicine；
--organize because any side effect does not occurs in the big mice safety testing in other acute toxicities, in
In normal range therefore do not present leukocyte numeral.)
In sum, the one that this case is provided utilizes metal ion to be combined micella technology cladding medicine
Thing amifostine or the method for other polyphenoils, to be applied to reduce radiation injury and chemotherapy
Drug side effect really belongs to innovation, there is no effective manner and go to control amifostine in past known techniques
Drug release, and provide intracorporeal organ selective distribution.Above-mentioned multinomial effect is real to be belonged to fully
Meeting the Statutory Invention patent requirement of novelty and progressive, filing an application in whence in accordance with the law, earnestly asks your office
Check and approve this part application for a patent for invention case, to encourage invention.
Claims (9)
1. a compound micellar carrier medical component is as the use preparing the medicine reducing free radical injury
On the way, it is characterised in that this compound micellar carrier medical component comprises:
At least one metal or its ion；
At least one medicine or by carrier protection and the polyphenoils modified, the most above-mentioned medicine or be subject to
Carrier protection and the polyphenoils modified are that coordination is binding on above-mentioned metal or its ion；And
Pharmaceutical carrier, the most above-mentioned pharmaceutical carrier is that coordination is binding on above-mentioned metal or its ion；
The most above-mentioned medicine or the polyphenoils by carrier protection and modification can be accumulated with throughout curve
With the effect that slowly release reduces free radical injury.
2. compound micellar carrier medical component as claimed in claim 1 reduces free radical as preparation
The purposes of the medicine of injury, it is characterised in that the most above-mentioned metal ion core is in following group
One or its combination in any or derivatives thereof: ferrum (Fe), copper (Cu), nickel (Ni), indium (In), calcium
(Ca), cobalt (Co), chromium (Cr), gadolinium (Gd), aluminum (Al), stannum (Sn), zinc (Zn), tungsten (W), scandium (Sc)
And titanium (Ti).
3. compound micellar carrier medical component as claimed in claim 1 reduces free radical as preparation
The purposes of the medicine of injury, it is characterised in that the most above-mentioned pharmaceutical carrier is selected from one of following group
Or its combination in any or derivatives thereof: Polyethylene Glycol (poly (ethylene glycol)), poly-Radix Asparagi
Propylhomoserin (poly (aspartic acid)), poly-glutamic acid (poly (glutamic acid)), poly-rely
Propylhomoserin (poly (lysine)), polyacrylic acid (poly (acrylic acid)), spherical chitosan
(chitosan), polymine (poly (ethyleneimine)), polymethylacrylic acid
(poly (methacrylic acid)), hyaluronic acid (hyaluronic acid), collagen protein
(collagen), poly-N-isopropylacrylamide (poly (N-isopropyl acrylamide)),
Amylose (amylose), cellulose (cellulose), poly butyric ester
(poly (hydroxybutyrate)), polylactic acid (poly (lacticacid)), poly-succinic acid butyl ester
(poly (butylenesuccinate)), polycaprolactone (poly (caprolactone)), carboxymethyl
Cellulose (carboxymethylcellulose), dextrin (dextran), cyclodextrin
(cyclodextrin), polyethylene glycol glutamic acid block copolymer (poly (ethylene
Glycol)-b-poly (glutamic acid)), phospholipid (phospholipid).
4. compound micellar carrier medical component as claimed in claim 1 reduces free radical as preparation
The purposes of the medicine of injury, it is characterised in that the most above-mentioned pharmaceutical carrier is selected from one of following group
Or its combination in any: micro-fat body, micella or macromolecule micella and dendrimer.
5. compound micellar carrier medical component as claimed in claim 1 reduces free radical as preparation
The purposes of the medicine of injury, it is characterised in that it further includes one or various medicine, and this medicine can be with metal
Bond or non-bond, the most above-mentioned medicine is selected from one of following group or its combination in any or it spreads out
Biological: amifostine (amifostine), WR-1065, vitamin C (ascorbicacid, Vitamin
C), glutathion (glutathione), Melatonin (melatonin), tocopherol
(tocopherols), tocotrienols (tocotrienols, Vitamin E), L-carnitine
(L-carnitine), carotene (carotenes), reduced form ubiquinone (ubiquinol), thioctic acid
(lipoicacid), polyphenol (polyphenols), catecholamine (catecholamine), curcumin
(curcumin), resveratrol (resveratrol), polydatin (piceid), mucolyticum
Acid (acetylcysteine), tetramethyl croak pyridine oxide (Tempo), asarone (asarone), ammonia
Base guanidine (aminoguanidine), vitamin E monoglycosides (tocopherol monoglucoside), sweet
Oxalic acid (glycyrrhizicacid), epicatechin (epicatechin), flavonoid (flavonoid),
Orientin (Orientin), Wei Caining (vicenin), 2-mercapto radical propionyl group-glycine
(MPG (2-mercaptopropionyl glycine)) and mesna (Mesna
(2-mercaptoethanesulfonic acid))。
6. the compound micellar carrier medical component as according to any one of claim 1 to 5 is as system
The purposes of medicine of low free radical of making preparation for dropping injury, it is characterised in that wherein this medicine can as reducing agent,
The biomolecule that reduction is aoxidized, to recover its function.
7. the compound micellar carrier medical component as according to any one of claim 1 to 5 is as system
The purposes of the medicine of low free radical of making preparation for dropping injury, it is characterised in that wherein this medicine can be imitated according to its antioxidation
Fruit stops free radical persistently to transmit and attack.
8. the compound micellar carrier medical component as according to any one of claim 1 to 5 is as system
The purposes of medicine of low free radical of making preparation for dropping injury, it is characterised in that wherein this medicine can reduce radiation,
The free radical that ultraviolet, chemotherapeutic drugs, Electromagnetic Environmental Effect etc. are caused, reaches to protect free radical injury
With the effect reducing its toxicity.
9. a compound micellar carrier medical component is as the use preparing the medicine reducing free radical injury
On the way, it is characterised in that this constituent comprises:
Iron ion；Amifostine；And pharmaceutical carrier, this carrier is polyethylene glycol glutamic acid block copolymerization
Thing；
The most above-mentioned amifostine is that coordination is binding on above-mentioned iron ion, the most above-mentioned pharmaceutical carrier
It is that coordination is binding on above-mentioned iron ion；
The most above-mentioned amifostine can reduce free radical wound with throughout curve accumulation with slowly release
The effect of evil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610455627.5A CN105997878B (en) | 2012-11-22 | 2012-11-22 | Reduce the compound micellar carrier medical component of free radical injury |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610455627.5A CN105997878B (en) | 2012-11-22 | 2012-11-22 | Reduce the compound micellar carrier medical component of free radical injury |
| CN201280054773.7A CN104114188A (en) | 2012-11-22 | 2012-11-22 | Pharmaceutical composition used for reducing damage caused by free radicals |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280054773.7A Division CN104114188A (en) | 2012-11-22 | 2012-11-22 | Pharmaceutical composition used for reducing damage caused by free radicals |
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| WO2023036347A1 (en) * | 2021-09-09 | 2023-03-16 | 原创生医股份有限公司 | Metal composite for ultrasonic contrast and use thereof |
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