CN105348410A - Iodine-containing polysaccharide as well as synthetic method and application thereof - Google Patents
Iodine-containing polysaccharide as well as synthetic method and application thereof Download PDFInfo
- Publication number
- CN105348410A CN105348410A CN201510929052.1A CN201510929052A CN105348410A CN 105348410 A CN105348410 A CN 105348410A CN 201510929052 A CN201510929052 A CN 201510929052A CN 105348410 A CN105348410 A CN 105348410A
- Authority
- CN
- China
- Prior art keywords
- polysaccharide
- iodine
- containing iodine
- phenyl triiodide
- derivatize
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0438—Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B31/00—Preparation of derivatives of starch
- C08B31/02—Esters
- C08B31/04—Esters of organic acids, e.g. alkenyl-succinated starch
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0018—Pullulan, i.e. (alpha-1,4)(alpha-1,6)-D-glucan; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
Abstract
The invention discloses a kind of polysaccharide containing iodine, it is characterized in that, for its molecular structure using hydrophilic natural polysaccharide as skeleton, general structure is as follows:
Wherein, R base is selected from the triiodo benzoyl of hydrogen or derivatization, and R is not all hydrogen; The structural formula of the triiodo benzoyl of derivatization are as follows:
Wherein, R ' base is selected from one or both of hydrogen, methyl, methylamino, acetylamino, N '-methylcarbamoyl, methoxyacetamido, N- methylacetamido or alkyl. High substitution polysaccharide containing iodine in the present invention is relative to small molecule containing iodine, and outstanding advantages are small molecules containing iodine by after producing high-molecular, and cytotoxicity substantially reduces, and there is no the small molecule leakage problems caused by spreading; In addition, CT contrast agent content of iodine of the invention is high, contrasting effects are good, cytotoxicity is low, clinical CT examination and diagnosis can be used for as a kind of blood pool contrast agent.
Description
Technical field
The invention belongs to macromolecular material and CT contrast medium field, particularly, relate to a kind of containing iodine polysaccharide and synthetic method thereof, and the application in preparation nanometer CT contrast medium.
Background technology
X-ray tomography (CT) is current one of most widely used noninvasive test method clinically, and it has wide range of applications, efficiency is high, speed is fast, expense is relatively low, can provide high precision non-overlapping three-dimensional tissue density image; In addition, CT technology the is had more wide application/upgrading space of the appearance (PET/CT, SPECT/CT) of some Combining diagnosis methods in the last few years.But the similar density of human body soft tissue, has close X-ray absorption coefficient; Some soft tissue is checked, CT contrast medium must be used to improve the contrast effect between tissue.At present, Clinical practice is the small molecules contrast medium containing iodine the most widely.Some contrast medium, such as Urogranoic acid
tM, is the ionic benzoic acid derivative containing phenyl triiodide, is expelled to after in body and can produces very high osmotic pressure, and the probability producing serious side effects is higher, and untoward reaction even may be caused even to suffer a shock, death; Small molecules contrast medium after some improvement, such as utravist (Ultravist)
tM, Omnipaque (Omnipaque)
tM, by ionic compound is changed into non-ionic type, or small molecules coupling is become dimer, can toxicity be reduced, reduce osmotic pressure, improve patient's tolerance.But, this micromolecular CT contrast medium because molecular weight low, in vivo circulation time can rapidly by kidney remove get rid of external, thus cause can development time short, interval check take and will need duplicate injection; In addition small molecules Iodine contrast medium can have distribution at Ink vessel transfusing and extravascular tissue, does not have tissue selectivity, causes CT radiography deterioration in accuracy.
Particle CT contrast medium containing the nanometer of iodine exists mainly with the form of micella, nanoparticle or nano-emulsion greatly, size is between 20-200 nanometer, can not be removed by kidney in blood, be distributed with specificity in vivo, may be used for blood pond radiography and liver, spleen, lymphography.Commercial nanoparticle contrast agent is as FenestraLC
tMand FenestraVC
tM, be contain iodine Witepsol W-S 55 emulsion, FenestraLC by the liquid state of polymeric surface active agent parcel
tMcan as liver cancer passive target contrast medium, FenestraVC
tMcan as long circulating contrast medium.Patent US20050036946A1 discloses a kind of common bio-medical material PEG, PEO-PPO-PEO, amphipathic degradable poly ester molecule etc. of using and modifies the method for phenyl triiodide formyl radical at chain end group, what it can be formed in aqueous solution self-assembly contains iodine nanoparticle, but the highest iodine content of its theory is low; Patent US8258190B2 will be loaded in as CT contrast medium in nanoparticle containing iodine small molecules bag, and its method is easy, but theoretical iodine content is low, and there is the shortcoming of leaking containing iodine small molecules.What have report to be formed by emulsion copolymerization by Triiodobenzoic acid methacrylate and other monomers in the document that can consult contains iodine microballoon or nanoparticle as CT contrast medium, its reaction is controlled, the nano-particles size of preparation is homogeneous, but this type of material is not biodegradable; What also have the lipiodol of use phosphatide, amphipathic nature polyalcohol and synthetic to prepare contains iodine nano-emulsion as CT contrast medium, and its iodine content is very high, but this type of emulsion intercalation method is not enough.By containing iodine group replace natural polysaccharide self-assembly preparation containing iodine nanoparticle CT contrast medium only have one example report (
biomaterials 2009,
30(29), 5667), the document, at cellulose acetate side chain graft 2,3,5-phenyl triiodide formyl radical, contains iodine nanoparticle CT contrast medium by the method preparation precipitated in the tween 80 aqueous solution; In the method, polysaccharide main chain is hydrophobic, cannot be self-assembled into nanoparticle in aqueous, can only form nanoparticle under the help of tensio-active agent after 2,3,5-phenyl triiodide formyl radicals of grafted hydrophobic; In addition, the iodine content of 2,3, the 5-phenyl triiodide formyl radical cellulose acetates that this method obtains is lower, and the nanoparticle poor stability of preparation, actual application value is low.Therefore, the nanoparticle CT contrast medium of high, the good stability of a kind of amount of iodine of preparation is needed badly.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, provide a kind of containing iodine polysaccharide.Of the present invention have higher iodine content containing iodine polysaccharide, and cytotoxicity reduces greatly, and do not exist by spreading the small molecules leakage problem caused.
Another object of the present invention is to provide the above-mentioned synthetic method containing iodine polysaccharide.
Another object of the present invention is to provide above-mentioned preparing containing the application in iodine nanoparticle CT contrast medium containing iodine polysaccharide.
Above-mentioned purpose of the present invention is achieved by the following technical programs.
A kind of containing iodine polysaccharide, its molecular structure is with hydrophilic natural polysaccharide for skeleton, and general structure is as follows:
Wherein, R is selected from alone the phenyl triiodide formyl radical of hydrogen or derivatize, and R is not hydrogen entirely; The structural formula of the phenyl triiodide formyl radical (TIB) of derivatize is:
Wherein, R ' base is selected from hydrogen (-H), methyl (-CH
3), methylamino-(-NHCH
3), kharophen (-NHCOCH
3), N '-methylcarbamoyl (-CONHCH
3), methoxyacetamido (-NHCOCH
2oCH
3), N-methylacetamido (-N (CH
3) COCH
3) or alkyl (-(CH
2) nCH
3) in one or both.Be modal situation when wherein R ' is two hydrogen, structure is the simplest, and in the phenyl triiodide formyl radical of now derivatize, the massfraction of iodine is the highest; When R ' for hydrogen and other substituting groups or be one or both in other substituting groups time, because substituent molecular weight is compared little with the molecular weight of three base benzoyls, so now derivatize group still has higher iodine content, what have the structure of this phenyl triiodide formyl radical also still has considerable iodine content containing iodine polysaccharide; And all possible R ' group chemical character is all very stable, all synthetic schemess of the present invention can be used to prepare.
Wherein long chain molecule is the schematic diagram of natural polysaccharide, is linked between sugared ring by glycosidic link, different natural polysaccharides have different chemical structures, conformation sugared ring element (
l,D), the mode of connection (α-Isosorbide-5-Nitrae glycosidic link, α-1,6 glycosidic link, α-2,6 glycosidic link, β-(1,3) glycosidic link) of different sugar interannular and different branching regime.
Natural polysaccharide wide material sources described in the present invention, good biocompatibility, can degradation in vivo, and unit mass number of functional groups on polysaccharide molecule is many, each sugared ring element contains three hydroxyls can be used for grafting containing iodine group, ensure that the final iodine polysaccharide that contains also has higher iodine content.
In the present invention containing iodine polysaccharide, be characterized in, when high graft(ing) degree (every 100 the sugared ring elements in DS=160 ~ 300), there is high iodine content, but be hydrophobic molecule; In low graft(ing) degree (DS=20 ~ 150) time be amphipathic molecule, have higher iodine content, can be self-assembled into stable containing iodine nanoparticle in aqueous, and still stablize under very high density; Lower graft(ing) degree containing iodine polysaccharide water soluble (DS=1 ~ 19).
Preferably, described natural polysaccharide is dextran, Pulan polysaccharide, starch, chitosan or schizophyllum abamectin.
Preferably; the phenyl triiodide formyl radical of described derivatize is 2; 3; 5-phenyl triiodide formyl radical, 4-methyl-6-acetylaminohydroxyphenylarsonic acid 2; 3,5-phenyl triiodide formyl radical, 4-methylamino--6-methoxyacetamido-2,3; 5-phenyl triiodide formyl radical, 2; 4,6-phenyl triiodide formyl radical, 3,5-dimethylaminos-2; 4; 6-phenyl triiodide formyl radical, 3-(N '-methylcarbamoyl)-5-(N-methylacetamido)-2,4,6-phenyl triiodide formyl radical or 3-methyl-5-alkyl-2; 4,6-phenyl triiodide formyl radical.The phenyl triiodide formyl radical of the derivatize of said structure all prepares by existing general chemical synthesis process.More preferably, the phenyl triiodide formyl radical of described derivatize is 2,3,5-phenyl triiodide formyl radical or 2,4,6-phenyl triiodide formyl radical.The structure of the phenyl triiodide formyl radical of above-mentioned two kinds of derivatizes is simple, and raw materials cost is low.
Preferably, on described polysaccharide molecule, the graft(ing) degree of the phenyl triiodide formyl radical of derivatize is 8 ~ 300, and above-mentioned graft(ing) degree is by every 100 sugared ring elements.More preferably; on described polysaccharide molecule, the graft(ing) degree of the phenyl triiodide formyl radical of derivatize is that 20 ~ 150(is by every 100 sugared ring elements); the iodine polysaccharide that contains within the scope of this graft(ing) degree not only has higher iodine content, and can be self-assembled into nanoparticle in aqueous.
A kind of described synthetic method containing iodine polysaccharide, adopt acyl chloride esterification method, be specially: described natural polysaccharide is heated to 90 DEG C under nitrogen protection condition, it is made to be dissolved in completely in solvent, cooling, add phenyl triiodide formyl chloride and the acid binding agent of derivatize under room temperature, after reaction for some time, purifying obtains containing iodine polysaccharide; The consumption of the phenyl triiodide formyl chloride of described derivatize is 0.1 ~ 4 times of natural polysaccharide sugar ring element (AGU) molar weight.
The structural formula of the phenyl triiodide formyl chloride (TIBC) of above-mentioned derivatize is:
Wherein, R ' is selected from alone hydrogen (-H), methyl (-CH
3), methylamino-(-NHCH
3), kharophen (-NHCOCH
3), N '-methylcarbamoyl (-CONHCH
3), methoxyacetamido (-NHCOCH
2oCH
3), N-methylacetamido (-N (CH
3) COCH
3) or alkyl (-(CH
2)
ncH
3) in one or both.
Preferably, the phenyl triiodide formyl chloride of described derivatize is 2,3,5-phenyl triiodide formyl chloride, 2,4,6-phenyl triiodide formyl chlorides.
Adopt acyl chloride esterification method, preferably, described natural polysaccharide is dextran, Pulan polysaccharide or starch.
Adopt acyl chloride esterification method, preferably, the consumption of the phenyl triiodide formyl chloride of described derivatize is 0.25 ~ 2 times of natural polysaccharide sugar ring element (AGU) molar weight, what obtain under this feed ratio contains iodine polysaccharide graft degree (by every 100 sugared ring elements) between 20 ~ 150, the iodine polysaccharide that contains within the scope of this graft(ing) degree not only has higher iodine content, and can be self-assembled into nanoparticle in aqueous.
Adopt acyl chloride esterification method, according to the difference of natural polysaccharide kind, preferably, described solvent is water, sodium hydroxide solution, N, dinethylformamide (DMF), the mixing of one or more in N,N-DIMETHYLACETAMIDE (DMAc), methane amide (formamide) or N-Methyl pyrrolidone (NMP) solvent.
Adopt acyl chloride esterification method, according to the difference of natural polysaccharide kind, preferably, be dissolved in completely in the process of solvent also add solubility promoter at described natural polysaccharide, described solubility promoter is Lithium chloride (anhydrous) (LiCl) or anhydrous lithium bromide (LiBr).
Adopt acyl chloride esterification method, according to the difference of natural polysaccharide kind, preferably, while the solution of phenyl triiodide formyl chloride adding derivatize, also catalyzer is added, described catalyzer is triethylamine (TEA), DMAP (DMAP) or 4-tetramethyleneimine pyridine (PP).
Adopt acyl chloride esterification method, according to the difference of natural polysaccharide kind and solvent for use, preferably, described acid binding agent is triethylamine, DMAP, pyridine (Py) or Anhydrous potassium carbonate (K
2cO
3).
Adopt acyl chloride esterification method, the phenyl triiodide formyl chloride of described derivatize, by conventional chemical synthetic method, such as, is obtained by reacting by the Triiodobenzoic acid of corresponding derivatize and thionyl chloride.
Adopt acyl chloride esterification method, preferably, the temperature of described reaction is 0 ~ 100 DEG C; The time of reaction is 1 ~ 24 hour.
Adopt acyl chloride esterification method, preferably, the concrete steps of described purifying are: dissolved in organic solvent by product, precipitate to remove remaining small molecules, several times repeatedly in methyl alcohol or ethanol, precipitate in water for the last time, dialysis, the hydrochloride that removing is remaining, freeze-drying, obtain white powder product, be containing iodine polysaccharide.
A kind of described synthetic method containing iodine polysaccharide, adopt DCC condensation esterification process, be specially: described natural polysaccharide is dissolved in organic solvent, N is added again after adding the Triiodobenzoic acid of DMAP (DMAP), derivatize, N'-dicyclohexylcarbodiimide (DCC), stirring at room temperature is reacted, and obtains containing iodine polysaccharide after purifying; The Triiodobenzoic acid of described derivatize, the consumption of N, N'-dicyclohexylcarbodiimide are 0.1 ~ 4 times of natural polysaccharide sugar ring element molar weight.
The structural formula of the Triiodobenzoic acid (TIBA) of above-mentioned derivatize is:
Wherein, R ' is selected from alone hydrogen (-H), methyl (-CH
3), methylamino-(-NHCH
3), kharophen (-NHCOCH
3), N '-methylcarbamoyl (-CONHCH
3), methoxyacetamido (-NHCOCH
2oCH
3), N-methylacetamido (-N (CH
3) COCH
3) or alkyl (-(CH
2) nCH
3) one or both.
Preferably, the Triiodobenzoic acid of described derivatize is 2,3,5 triiodobenzoic acid, 2,4,6-Triiodobenzoic acids.
Adopt DCC condensation esterification process, preferably, described natural polysaccharide is dextran, Pulan polysaccharide or starch.
Adopt DCC condensation esterification process, preferably, the consumption of the Triiodobenzoic acid of described derivatize is 0.25 ~ 2 times of natural polysaccharide sugar ring element (AGU) molar weight.What obtain under this kind of feed ratio contains iodine polysaccharide graft degree (by every 100 sugared ring elements) between 20 ~ 150, and the iodine polysaccharide that contains within the scope of this graft(ing) degree not only has higher iodine content, and can be self-assembled into nanoparticle in aqueous.
Adopt DCC condensation esterification process, preferably, the time of described reaction is 12 ~ 48 hours.
Adopt DCC condensation esterification process, according to the difference of natural polysaccharide kind, preferably, described organic solvent is N, dinethylformamide (DMF), the mixing of one or more in N,N-DIMETHYLACETAMIDE (DMAc), methane amide (formamide) or N-Methyl pyrrolidone (NMP) or methylene dichloride.
Adopt DCC condensation esterification process, according to the difference of natural polysaccharide kind, preferably, while described natural polysaccharide is dissolved in organic solvent, also add solubility promoter, described solubility promoter is Lithium chloride (anhydrous) (LiCl) or or anhydrous lithium bromide (LiBr).
Adopt DCC condensation esterification process, preferably, the concrete steps of described purifying are: be dissolved in by product in a small amount of organic solvent, be added drop-wise to after cold filtration in methyl alcohol and precipitate with the DCU generated except dereaction and unreacted small molecules, several times repeatedly, vacuum-drying, obtains containing iodine polysaccharide.
A kind of described synthetic method containing iodine polysaccharide, adopt CDI condensation esterification process, be specially: the Triiodobenzoic acid of derivatize is dissolved in organic solvent, add N, N '-carbonyl dimidazoles (Carbonyldiimidazole, CDI), 60 DEG C are reacted room temperature after 4 hours and continue reaction 20 hours, obtain Orazamide intermediate; Be dissolved in organic solvent by described natural polysaccharide again, join in Orazamide midbody solution, stirring at room temperature reacts 24 hours, obtains containing iodine polysaccharide after purifying; The Triiodobenzoic acid of described derivatize, N, N ' consumption of-carbonyl dimidazoles (CDI) is equal, and be 0.1 ~ 4 times of polysaccharide sugar ring molar weight.
The structural formula of the Triiodobenzoic acid (TIBA) of above-mentioned derivatize is:
Wherein, R ' is selected from alone hydrogen (-H), methyl (-CH
3), methylamino-(-NHCH
3), kharophen (-NHCOCH
3), N '-methylcarbamoyl (-CONHCH
3), methoxyacetamido (-NHCOCH
2oCH
3), N-methylacetamido (-N (CH
3) COCH
3) or alkyl (-(CH
2) nCH
3) in one or both.
Preferably, described Triiodobenzoic acid is 2,3,5 triiodobenzoic acid, 2,4,6-Triiodobenzoic acids.
Adopt CDI condensation esterification process, preferably, described natural polysaccharide is dextran, Pulan polysaccharide or starch.
Adopt CDI condensation esterification process, preferably, the consumption of the Triiodobenzoic acid of described derivatize is 0.25 ~ 2 times of natural polysaccharide sugar ring element (AGU) molar weight.What obtain under this kind of feed ratio contains iodine polysaccharide graft degree (by every 100 sugared ring elements) between 20 ~ 150, and the iodine polysaccharide that contains within the scope of this graft(ing) degree not only has higher iodine content, and can be self-assembled into nanoparticle in aqueous.
Adopt CDI condensation esterification process, according to the difference of natural polysaccharide kind, preferably, described organic solvent is dimethyl sulfoxide (DMSO) (DMSO), DMF (DMF), the mixing of one or more in N,N-DIMETHYLACETAMIDE (DMAc) or N-Methyl pyrrolidone (NMP).
Adopt CDI condensation esterification process, according to the difference of natural polysaccharide kind, preferably, while described natural polysaccharide is dissolved in organic solvent, also add solubility promoter, described solubility promoter is Lithium chloride (anhydrous) (LiCl), anhydrous lithium bromide (LiBr) or tetrabutyl ammonium fluoride (TBAF).
Adopt CDI condensation esterification process, preferably, the concrete steps of described purifying are: dissolved in organic solvent by product, be added drop-wise in methyl alcohol and precipitate to remove unreacted small molecules, several times repeatedly, vacuum-drying, obtain containing iodine polysaccharide.
The described iodine polysaccharide that contains is being prepared containing the application in iodine nanoparticle CT contrast medium.
Preferably, be dissolved in organic solvent, be slowly added drop-wise to described in water under agitation condition containing iodine polysaccharide with the concentration of 2 ~ 50mg/mL, dialysis removing organic solvent, namely obtains described CT contrast medium after centrifugal concentrating.
Preferably, the described graft(ing) degree containing iodine polysaccharide is 20 ~ 150, and above-mentioned graft(ing) degree is by every 100 sugared ring elements.
Preferably, described organic solvent is dimethyl sulfoxide (DMSO) (DMSO) or N,N-DIMETHYLACETAMIDE (DMAc).
Compared with prior art, beneficial effect of the present invention is: in the present invention containing iodine polysaccharide, its iodine content greatly exceed the urethane replaced containing iodine group in bibliographical information, with containing the poly(lactic acid) of iodine chainextender chain extension, or other classes reported are containing iodine macromolecular material.In the present invention, high replacement, contains iodine polysaccharide relative to the small molecules containing iodine, and its outstanding advantages is containing iodine small molecules by after high molecular, very low to the toxicity of cell, and does not exist by spreading the small molecules leakage problem caused; In addition, the high iodine content in nanoparticle and the stability under high density ensure that this nanoparticle CT contrast medium has good contrasting effects.
CT contrast medium of the present invention, its highest iodine content can reach 150mgI/mL, and external CT experiment shows to have extraordinary contrast ability.
Accompanying drawing explanation
Fig. 1 be use in embodiment 1 different feed ratio be the different graft(ing) degrees obtained containing iodine polysaccharide product proton nmr spectra (
1h-NMR).(a) dextran; B () feed ratio 0.3, containing iodine polysaccharide DS=0.26; C () feed ratio 1.0, containing iodine polysaccharide DS=0.9; D () feed ratio 3.0, containing iodine polysaccharide DS=2.8.
Fig. 2 is transmission electron microscope (TEM) photo containing iodine nanoparticle in embodiment 9.
Fig. 3 is the external contrasting effects that in embodiment 10, nanoparticle CT contrast medium is tested on Micro-CT machine.
Embodiment
Below in conjunction with Figure of description and specific embodiment, the present invention is described in further details, but embodiment does not limit in any form the present invention.Unless stated otherwise, the present invention adopts reagent, method and apparatus are the art conventional reagent, method and apparatus.
Embodiment 1 ~ 6 is the dissimilar embodiment containing iodine polysaccharide and synthetic method thereof.Synthesize in embodiment containing iodine polysaccharide graft degree by proton nmr spectra (
1h-NMR) test, iodine content uses oxygen combustion to clear up the test of rear chemistry titration by Sch niger method.
Embodiment 7 ~ 9 for use synthesis containing iodine polysaccharide prepare containing the embodiment applied in iodine nanoparticle CT contrast medium.Containing iodine nanoparticle by dynamic light scattering method test fluid flow mechanics radius, by transmission electron microscope observing nanoparticle pattern; The external contrast ability of nanoparticle suspension is measured by Micro-CT.
Embodiment 10 is the specific implementation method using Micro-CT vitro test contrast ability containing iodine nanoparticle CT contrast medium.
embodiment 1(dextran 2,3,5 triiodobenzoic acid ester-acyl chloride esterification method)
Dextran 2,3,5 triiodobenzoic acid ester, its general formula of molecular structure is as follows:
Wherein, R is selected from hydrogen or 2,3,5-phenyl triiodide formyl radical, and R is not hydrogen entirely, and the graft(ing) degree of 2,3,5-phenyl triiodide formyl radical is that 8 ~ 300(is in every 100 sugared ring elements).
The above-mentioned iodine polysaccharide that contains synthesizes as follows: join in 50mLDMAc by dextran (Dextran, 2g, 12.3mmolAGU) and lithium chloride (2g) under nitrogen protection condition, be heated to 90 DEG C, make it dissolve completely, cooling; Catalytic amount DMAP is added under room temperature, and acid binding agent triethylamine (with 2,3,5-phenyl triiodide formyl chloride equivalent) and different 2,3, the 5-phenyl triiodide formyl chloride (1.23 ~ 49.2mmol measured, namely the ratio of 2,3,5-phenyl triiodide formyl chlorides and dextran AGU molar weight is 0.1 ~ 4) DMF solution 50mL, 70 DEG C of reactions 1 hour, methanol extraction, dissolved with DMSO repeatedly, precipitate in methyl alcohol repeatedly, finally dissolve in DMSO, precipitate in water, dialysis, freeze-drying white powder is containing iodine polysaccharide.After tested, in dextran 2,3,5 triiodobenzoic acid ester, the graft(ing) degree of 2,3,5-phenyl triiodide formyl radicals increases along with the charging capacity increase of 2,3,5-phenyl triiodide formyl chloride, is 8 ~ 300, by every 100 sugared rings.When feed ratio is 0.1, be that 8(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is minimum, is 15%; When feed ratio is 4, be that 300(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is the highest, is 71%; Thus this is 15 ~ 71% containing iodine polysaccharide iodine content.
The proton nmr spectra of the dextran 2,3,5 triiodobenzoic acid ester of raw material dextran and three kinds of graft(ing) degrees as shown in Figure 1, (a) dextran; B () feed ratio 0.3, containing iodine polysaccharide DS=0.26; C () feed ratio 1.0, containing iodine polysaccharide DS=0.9; D () feed ratio 3.0, containing iodine polysaccharide DS=2.8.
embodiment 2 (dextran 2,4,6-Triiodobenzoic acid ester DCC method)
Dextran 2,4,6-Triiodobenzoic acid ester, its general formula of molecular structure is as follows:
Wherein, R is selected from hydrogen or 2,4,6-phenyl triiodide formyl radical, and R is not hydrogen entirely, and the graft(ing) degree of 2,3,5-phenyl triiodide formyl radical is that 8 ~ 300(is in every 100 sugared ring elements).
The above-mentioned iodine polysaccharide that contains synthesizes as follows: join in 50mLDMAc by dextran (Dextran, 2g, 12.3mmolAGU) and lithiumbromide (2g) under nitrogen protection condition, be heated to 90 DEG C, make it dissolve completely, cooling; Add 2 of catalytic amount DMAP and different amount, 4,6-Triiodobenzoic acid (1.23 ~ 49.2mmol, namely 2,4, the ratio of 6-Triiodobenzoic acid and dextran AGU molar weight is 0.1 ~ 4) after add DCC(and 2 again, 4,6-Triiodobenzoic acid equivalent), stirring at room temperature is reacted, methanol extraction after filtering, obtains after purifying containing iodine polysaccharide.After tested, in dextran 2,4,6-Triiodobenzoic acid ester, the graft(ing) degree of 2,4,6-phenyl triiodide formyl radicals increases along with the charging capacity increase of 2,4,6-Triiodobenzoic acid, is that 8 ~ 300(is by every 100 sugared rings).When feed ratio is 0.1, be that 8(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is minimum, is 15%; When feed ratio is 4, be 300 by every 100 sugared rings containing iodine polysaccharide graft degree, iodine content is the highest, is 71%; Thus this is 15 ~ 71% containing iodine polysaccharide iodine content.
embodiment 3 (Pulan polysaccharide 2,3,5 triiodobenzoic acid ester DCC method)
Pulan polysaccharide 2,3,5 triiodobenzoic acid ester, its general formula of molecular structure is as follows:
Wherein, R is selected from hydrogen or 2,3,5-phenyl triiodide formyl radical, and R is not hydrogen entirely, and the graft(ing) degree of 2,3,5-phenyl triiodide formyl radical is that 8 ~ 300(is in every 100 sugared ring elements).
The above-mentioned iodine polysaccharide that contains synthesizes as follows: join in 50mLDMF by Pulan polysaccharide (Pullulan, 2g, 12.3mmolAGU) and lithium chloride (2g) under nitrogen protection condition, be heated to 90 DEG C, make it dissolve completely, cooling; Add catalytic amount DMAP, 2,3,5 triiodobenzoic acid (1.23 ~ the 49.2mmol of different amount, namely 2, the ratio of 3,5-Triiodobenzoic acid and Pulan Polysaccharide A GU molar weight is 0.1 ~ 4) after add DCC(and 2 again, 3,5-Triiodobenzoic acid equivalent), stirring at room temperature is reacted, methanol extraction after filtering, and obtains containing iodine polysaccharide after purifying.After tested, in the polysaccharide 2,3,5 triiodobenzoic acid ester of Pulan, the graft(ing) degree of 2,3,5-phenyl triiodide formyl radicals increases along with the charging capacity increase of 2,3,5-phenyl triiodide formylamino acid, is that 8 ~ 300(is by every 100 sugared rings).When feed ratio is 0.1, be that 8(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is minimum, is 15%; When feed ratio is 4, be 300 by every 100 sugared rings containing iodine polysaccharide graft degree, iodine content is the highest, is 71%; Thus this is 15 ~ 71% containing iodine polysaccharide iodine content.
embodiment 4 (Pulan polysaccharide 2,4,6-Triiodobenzoic acid ester CDI method)
Pulan polysaccharide 2,4,6-Triiodobenzoic acid ester, general formula of molecular structure is as follows:
Wherein, R is selected from hydrogen or 2,3,5-phenyl triiodide formyl radical, and R is not hydrogen entirely, and the graft(ing) degree of 2,3,5-phenyl triiodide formyl radical is that 8 ~ 300(is in every 100 sugared ring elements).
The above-mentioned iodine polysaccharide that contains synthesizes as follows: by 2 of difference amount, 4,6-Triiodobenzoic acid (1.23 ~ 49.2mmol, namely 2,4, the ratio of 6-Triiodobenzoic acid and Pulan Polysaccharide A GU molar weight is 0.1 ~ 4) be dissolved in DMSO, add equivalent CDI(and 2,4,6-Triiodobenzoic acid equivalent), 60 DEG C are reacted room temperature after 4 hours and continue reaction 20 hours, obtain Orazamide intermediate; After Pulan polysaccharide (2g, 12.3mmolAGU) is directly dissolved into DMSO, join in Orazamide midbody solution, stirring at room temperature reacts 24 hours, methanol extraction, obtains containing iodine polysaccharide after purifying.After tested, in Pulan polysaccharide 2,4,6-Triiodobenzoic acid ester, the graft(ing) degree of 2,4,6-phenyl triiodide formyl radicals increases along with the charging capacity increase of 2,4,6-Triiodobenzoic acid, is 8 ~ 300, by every 100 sugared rings.When feed ratio is 0.1, be that 8(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is minimum, is 15%; When feed ratio is 4, be that 300(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is the highest, is 71%; Thus this is 15 ~ 71% containing iodine polysaccharide iodine content.
embodiment 5 (starch 2,3,5 triiodobenzoic acid ester CDI method)
Starch 2,3,5 triiodobenzoic acid ester, its general formula of molecular structure is as follows:
Wherein, R is selected from hydrogen or 2,3,5-phenyl triiodide formyl radical, and R is not hydrogen entirely, and the graft(ing) degree of 2,3,5-phenyl triiodide formyl radical is that 8 ~ 300(is in every 100 sugared ring elements).
The above-mentioned iodine polysaccharide that contains synthesizes as follows: by 2 of difference amount, 3,5-Triiodobenzoic acid (1.23 ~ 49.2mmol, namely 2,3, the ratio of 5-Triiodobenzoic acid and starch AGU molar weight is 0.1 ~ 4) be dissolved in DMAc, add equivalent CDI(and 2,3,5 triiodobenzoic acid equivalent), 60 DEG C are reacted room temperature after 4 hours and continue reaction 20 hours, obtain Orazamide intermediate; Starch (Amylose, 2g, 12.3mmolAGU) and lithium chloride (2g) are heated to 90 DEG C to be dissolved in DMAc, and join in Orazamide midbody solution after cooling, stirring at room temperature reacts 24 hours, methanol extraction, obtains containing iodine polysaccharide after purifying.After tested, in starch 2,3,5 triiodobenzoic acid ester, the graft(ing) degree of 2,3,5-phenyl triiodide formyl radicals increases along with the charging capacity increase of 2,3,5 triiodobenzoic acid, is 8 ~ 300, by every 100 sugared rings.When feed ratio is 0.1, be that 8(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is minimum, is 15%; When feed ratio is 4, be that 300(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is the highest, is 71%; Thus this is 15 ~ 71% containing iodine polysaccharide iodine content.
embodiment 6(starch 2,4,6-Triiodobenzoic acid ester-acyl chloride esterification method)
Starch 2,4,6-Triiodobenzoic acid ester, general formula of molecular structure is as follows:
Wherein, R is selected from hydrogen or 2,4,6-phenyl triiodide formyl radical, and R is not hydrogen entirely, and the graft(ing) degree of 2,4,6-phenyl triiodide formyl radical is that 8 ~ 300(is in every 100 sugared ring elements).
The above-mentioned iodine polysaccharide that contains synthesizes as follows: by starch (Amylose, 2g, 12.3mmolAGU) join in 50mLDMF with lithiumbromide (2g) under nitrogen protection condition, be heated to 90 DEG C, it is made to dissolve completely, cooling, adds DMAP(and 2,4 under room temperature, 6-phenyl triiodide formyl chloride equivalent) and different amount 2,4,6-phenyl triiodide formyl chloride (1.23 ~ 49.2mmol, namely 2,4, the ratio of 6-phenyl triiodide formyl chloride and starch AGU molar weight is 0.1 ~ 4) DMF solution 50mL, 100 DEG C reaction 5 hours, methanol extraction; Product dissolves with DMSO repeatedly, precipitates repeatedly, finally precipitating in water in methyl alcohol, dialysis, and freeze-drying obtains white powder containing iodine polysaccharide.After tested, in starch 2,4,6-Triiodobenzoic acid ester, the graft(ing) degree of 2,4,6-phenyl triiodide formyl radicals increases along with the charging capacity increase of 2,4,6-phenyl triiodide formyl chloride, is 8 ~ 300, by every 100 sugared rings.When feed ratio is 0.1, be that 8(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is minimum, is 15%; When feed ratio is 4, be that 300(is by every 100 sugared rings containing iodine polysaccharide graft degree), iodine content is the highest, is 71%; Thus this is 15 ~ 71% containing iodine polysaccharide iodine content.
embodiment 7
Starch 2,4,6-Triiodobenzoic acid ester, is prepared by embodiment 6, and the graft(ing) degree choosing wherein 2,4,6-phenyl triiodide formyl radicals is that 20(is by every 100 sugared ring elements) product for the preparation of CT contrast medium.This graft(ing) degree obtains product when being using the reaction of 2,4, the 6-phenyl triiodide formyl chlorides (feed ratio is 0.25) of 3.08mmol containing iodine polysaccharide, and its iodine content is 34% after measured.
Be dissolved in DMSO containing iodine polysaccharide with the concentration of 2mg/mL by above-mentioned, be then under agitation slowly added drop-wise in pure water, dialysis removing organic solvent, high speed centrifugation concentrates, and to obtain final product.
After tested, this nanoparticle CT contrast medium iodine concentration is 50mgI/mL, is 250nm containing iodine nano particle diameter.
embodiment 8
Pulan polysaccharide 2,4,6-Triiodobenzoic acid ester, is prepared by embodiment 4, and the graft(ing) degree choosing wherein 2,4,6-phenyl triiodide formyl radicals is that 90(is by every 100 sugared ring elements) product for the preparation of CT contrast medium.This graft(ing) degree obtains product when being using the reaction of 2,4, the 6-phenyl triiodide formyl chlorides (feed ratio is 1) of 12.30mmol containing iodine polysaccharide, and its iodine content is 58% after measured.
Be dissolved in DMSO containing iodine polysaccharide with the concentration of 50mg/mL by above-mentioned, be then under agitation slowly added drop-wise in pure water, dialysis removing organic solvent, high speed centrifugation concentrates, and to obtain final product.
After tested, this nanoparticle CT contrast medium iodine concentration is 150mgI/mL, is 40nm containing iodine nano particle diameter.
embodiment 9
Dextran 2,3,5 triiodobenzoic acid ester, is prepared by embodiment 1, and the graft(ing) degree choosing wherein 2,3,5-phenyl triiodide formyl radicals is that 150(is by every 100 sugared ring elements) product for the preparation of CT contrast medium.This graft(ing) degree obtains product when being using the reaction of 2,4, the 6-phenyl triiodide formyl chlorides (feed ratio is 2) of 24.60mmol containing iodine polysaccharide, and its iodine content is 65% after measured.
Be dissolved in DMAc containing iodine polysaccharide with the concentration of 10mg/mL by above-mentioned, be then under agitation slowly added drop-wise in pure water, dialysis removing organic solvent, high speed centrifugation concentrates, and to obtain final product.
After tested, this nanoparticle CT contrast medium iodine concentration is 110mgI/mL, is 120nm containing iodine nano particle diameter.
Fig. 2 is transmission electron microscope (TEM) photo that the present embodiment contains iodine nanoparticle.
embodiment 10
Containing iodine polysaccharide nano particle CT contrast medium, being prepared by embodiment 9, be 120nm, CT contrast medium iodine concentration is wherein 110mgI/mL containing iodine nano particle diameter.
Get containing iodine polysaccharide nano particle CT contrast medium the gland plastic centrifuge tube that about 0.5mL puts into 2mL by above-mentioned; Micro-CT instrument is used to carry out testing (Nano-X/CT; TriFoilImaging; USA); experiment condition is as follows: bulb voltage 65kVp; tube current 0.123mA, detector size 77 μm; Pitch 0.4mm, preposition aluminium filter thickness is 0.5mm.Test result shows that its CT value is 2991 ± 234HU with this understanding, and the CT value that the content of its CT value and the iodine contained by it should have is corresponding.
Fig. 3 is the comparison diagram of external contrasting effects and the pure water tested on Micro-CT machine containing iodine polysaccharide nano particle CT contrast medium in the present embodiment.
Claims (10)
1., containing an iodine polysaccharide, it is characterized in that, its molecular structure is with hydrophilic natural polysaccharide for skeleton, and general structure is as follows:
Wherein, R base is selected from the phenyl triiodide formyl radical of hydrogen or derivatize, and R is not hydrogen entirely; The structural formula of the phenyl triiodide formyl radical of described derivatize is:
Wherein, R ' base is selected from one or both in hydrogen, methyl, methylamino-, kharophen, N '-methylcarbamoyl, methoxyacetamido, N-methylacetamido or alkyl.
2. according to claim 1 containing iodine polysaccharide, it is characterized in that, described natural polysaccharide is dextran, Pulan polysaccharide, starch, chitosan or schizophyllum abamectin.
3. according to claim 1 containing iodine polysaccharide; it is characterized in that; the phenyl triiodide formyl radical of described derivatize is 2; 3,5-phenyl triiodide formyl radical, 4-methyl-6-acetylaminohydroxyphenylarsonic acid 2,3; 5-phenyl triiodide formyl radical, 4-methylamino--6-methoxyacetamido-2; 3,5-phenyl triiodide formyl radical, 2,4; 6-phenyl triiodide formyl radical, 3; 5-dimethylamino-2,4,6-phenyl triiodide formyl radical, 3-(N '-methylcarbamoyl)-5-(N-methylacetamido)-2; 4; 6-phenyl triiodide formyl radical or 3-methyl-5-n-heptyl-2,4,6-phenyl triiodide formyl radical.
4. according to claim 1 containing iodine polysaccharide, it is characterized in that, on described polysaccharide molecule, the graft(ing) degree of derivatize phenyl triiodide formyl radical is 8 ~ 300, and above-mentioned graft(ing) degree is by every 100 sugared ring elements.
5. described in any one of claim 1 ~ 4, contain the synthetic method of iodine polysaccharide, it is characterized in that, adopt acyl chloride esterification method, be specially: described natural polysaccharide is heated to 90 DEG C under nitrogen protection condition, make it be dissolved in completely in solvent, cooling, adds phenyl triiodide formyl chloride and the acid binding agent of derivatize under room temperature, after reaction for some time, purifying obtains containing iodine polysaccharide; The consumption of the phenyl triiodide formyl chloride of described derivatize is 0.1 ~ 4 times of natural polysaccharide sugar ring element molar weight.
6. described in any one of claim 1 ~ 4, contain the synthetic method of iodine polysaccharide, it is characterized in that, adopt DCC condensation esterification process, be specially: described natural polysaccharide is dissolved in organic solvent, N is added again after adding the Triiodobenzoic acid of DMAP, derivatize, N'-dicyclohexylcarbodiimide, stirring at room temperature is reacted, and obtains containing iodine polysaccharide after purifying; The Triiodobenzoic acid of described derivatize, the consumption of N, N'-dicyclohexylcarbodiimide are 0.1 ~ 4 times of natural polysaccharide sugar ring element molar weight.
7. described in any one of claim 1 ~ 4, contain the synthetic method of iodine polysaccharide, it is characterized in that, adopt CDI condensation esterification process, be specially: the Triiodobenzoic acid of derivatize is dissolved in organic solvent, add N, N '-carbonyl dimidazoles, 60 DEG C are reacted room temperature after 4 hours and continue reaction 20 hours, obtain Orazamide intermediate; Be dissolved in organic solvent by described natural polysaccharide again, join in Orazamide midbody solution, stirring at room temperature reacts 24 hours, obtains containing iodine polysaccharide after purifying; The Triiodobenzoic acid of described derivatize, N, N ' consumption of-carbonyl dimidazoles is equal, and be 0.1 ~ 4 times of polysaccharide sugar ring molar weight.
8. preparing containing the application in iodine nanoparticle CT contrast medium containing iodine polysaccharide described in any one of claim 1 ~ 4.
9. application according to claim 8, is characterized in that, is dissolved in organic solvent, is added drop-wise to described in pure water under agitation condition containing iodine polysaccharide with the concentration of 2 ~ 50mg/mL, and dialysis removing organic solvent, namely obtains described CT contrast medium after centrifugal concentrating.
10. application according to claim 9, is characterized in that, the described graft(ing) degree containing iodine polysaccharide is 20 ~ 150, and above-mentioned graft(ing) degree is by every 100 sugared ring elements.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510929052.1A CN105348410B (en) | 2015-12-14 | 2015-12-14 | One kind polysaccharide containing iodine and its synthetic method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510929052.1A CN105348410B (en) | 2015-12-14 | 2015-12-14 | One kind polysaccharide containing iodine and its synthetic method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105348410A true CN105348410A (en) | 2016-02-24 |
| CN105348410B CN105348410B (en) | 2019-02-26 |
Family
ID=55324488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510929052.1A Active CN105348410B (en) | 2015-12-14 | 2015-12-14 | One kind polysaccharide containing iodine and its synthetic method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105348410B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111825776A (en) * | 2020-06-10 | 2020-10-27 | 青岛海大生物集团有限公司 | Preparation process and application of halogenated algal polysaccharide |
| US10918742B2 (en) * | 2016-03-25 | 2021-02-16 | Nanoprobes, Inc. | Iodine-based particles |
| CN114573721A (en) * | 2022-03-17 | 2022-06-03 | 今禾方吟科技(深圳)有限责任公司 | Quickly degradable biological plastic and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5886169A (en) * | 1987-02-13 | 1999-03-23 | Guerbet S.A. | Iodinated polymers, processes for preparing them and their applications as contrast media |
| CN101544701A (en) * | 2009-04-28 | 2009-09-30 | 山东省医疗器械研究所 | Developable iodic polymer and embolic material thereof |
| WO2009158290A2 (en) * | 2008-06-25 | 2009-12-30 | Abbott Cardiovascular Systems Inc. | Implantable medical devices fabricated from radiopaque polymers with high fracture toughness |
| CN101945672A (en) * | 2007-12-21 | 2011-01-12 | 艾奥弗尔玛科技公司 | Biodegradable contrast agents |
| CN102100933A (en) * | 2010-08-10 | 2011-06-22 | 微创医疗器械(上海)有限公司 | Embolic material composition and preparation method thereof |
-
2015
- 2015-12-14 CN CN201510929052.1A patent/CN105348410B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5886169A (en) * | 1987-02-13 | 1999-03-23 | Guerbet S.A. | Iodinated polymers, processes for preparing them and their applications as contrast media |
| CN101945672A (en) * | 2007-12-21 | 2011-01-12 | 艾奥弗尔玛科技公司 | Biodegradable contrast agents |
| WO2009158290A2 (en) * | 2008-06-25 | 2009-12-30 | Abbott Cardiovascular Systems Inc. | Implantable medical devices fabricated from radiopaque polymers with high fracture toughness |
| CN101544701A (en) * | 2009-04-28 | 2009-09-30 | 山东省医疗器械研究所 | Developable iodic polymer and embolic material thereof |
| CN102100933A (en) * | 2010-08-10 | 2011-06-22 | 微创医疗器械(上海)有限公司 | Embolic material composition and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| ZVI COHEN ET AL.: ""Iodinated Starch Particles：New Contrast Materials for Computed Tomography of the Liver"", 《JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10918742B2 (en) * | 2016-03-25 | 2021-02-16 | Nanoprobes, Inc. | Iodine-based particles |
| CN111825776A (en) * | 2020-06-10 | 2020-10-27 | 青岛海大生物集团有限公司 | Preparation process and application of halogenated algal polysaccharide |
| CN114573721A (en) * | 2022-03-17 | 2022-06-03 | 今禾方吟科技(深圳)有限责任公司 | Quickly degradable biological plastic and preparation method thereof |
| CN114573721B (en) * | 2022-03-17 | 2023-07-25 | 壹科环塑新材料科技(深圳)有限公司 | Rapidly degradable biological plastic and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105348410B (en) | 2019-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ooi et al. | Cellulose nanocrystals extracted from rice husks as a reinforcing material in gelatin hydrogels for use in controlled drug delivery systems | |
| US7030208B2 (en) | Biocompatible materials and probes | |
| CN111621038B (en) | Albumin hydrogel, and preparation method and application thereof | |
| CN107096036B (en) | Preparation method and application of pH-sensitive hyaluronic acid-doxorubicin nano prodrug | |
| US8445465B2 (en) | Glycol chitosan derivative, preparation method thereof and drug delivery system comprising the same | |
| CN103656652B (en) | A kind of sensitive response type polymer nano-micelle and its preparation method and application | |
| CN105348410A (en) | Iodine-containing polysaccharide as well as synthetic method and application thereof | |
| Elshaarani et al. | Dextran-crosslinked glucose responsive nanogels with a self-regulated insulin release at physiological conditions | |
| CN101979096B (en) | Gold and iodine element-supported arborescent macromolecular computed tomography (CT) targeted contrast medium and preparation thereof | |
| Yu et al. | Grafting modification of chitosan | |
| Vildanova et al. | Preparation and rheological properties of hydrogels based on N-succinyl chitosan and hyaluronic acid dialdehyde | |
| CN105859990B (en) | The polymer of side chain sulfur-bearing caprylyl, its preparation method and polymer vesicle prepared therefrom and its application | |
| WO2014190849A1 (en) | Doxorubicin prodrug, method of preparing same, and injectable combination | |
| Peng et al. | Cyclodextrin/dextran based drug carriers for a controlled release of hydrophobic drugs in zebrafish embryos | |
| Pourbadiei et al. | Synthesis and characterization of dual light/temperature-responsive supramolecular injectable hydrogel based on host-guest interaction between azobenzene and starch-grafted β-cyclodextrin: Melanoma therapy with paclitaxel | |
| CN109044963A (en) | A kind of injection pH sensitivity nano-hydrogel and preparation method thereof | |
| CN113801344B (en) | Oxygen-loaded fluorine-containing temperature-sensitive hydrogel and preparation method and application thereof | |
| Tao et al. | Modular synthesis of amphiphilic chitosan derivatives based on copper-free click reaction for drug delivery | |
| Chisty et al. | PEGylated chitin and chitosan derivatives | |
| Jeon et al. | pH-Responsive hyaluronic acid-based nanocarrier for treatment of rheumatoid arthritis | |
| JP2000086538A (en) | Contrast medium for mri | |
| WO2012021046A9 (en) | Radial shape of polymer compound containing iodine, preparation method thereof, and ct contrast medium composition containing same | |
| CN104622813A (en) | Nano microspheres formed based on host-guest interaction as well as preparation method and application of nano microspheres | |
| CN111603565A (en) | Anti-inflammatory nano-drug carrier, pharmaceutical composition thereof, preparation method and application | |
| CN107337653B (en) | tetraiodothyronine-N-carboxyl internal acid anhydride, poly-tetraiodothyronine and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |