CN105582020A - Application of linear polythiourea and hyperbranched polythiourea in preparation of anti-tumor medicines and anti-virus or anti-bacterial medicines - Google Patents
Application of linear polythiourea and hyperbranched polythiourea in preparation of anti-tumor medicines and anti-virus or anti-bacterial medicines Download PDFInfo
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Abstract
The invention discloses an application of linear polythiourea in preparation of anti-tumor medicines and anti-virus or anti-bacterial medicines. The linear polythiourea has the structural formula represented as the formula (I), wherein R1 and R2 are independently selected from hydrogen, C1-C10 alkyl groups and aryl groups, or a hetero atom group containing N, O and S. The number-average molecular weight of the linear polythiourea is 50-50000. The invention also discloses an application of hyperbranched polythiourea in preparation of anti-tumor medicines and anti-virus or anti-bacterial medicines. The hyperbranched polythiourea is prepared by dissolving a monomer containing at least two isothiocyanic acid groups or dissolving thiourea with a monomer containing at least two amine groups in an organic solvent, performing a heating condensation polymerization reaction under protection of an inert gas, and purifying a reaction product to prepare the hyperbranched polythiourea.
Description
Technical field
The invention belongs to the technical field of polymer applications, be specifically related to a kind of linear polythiourea and over-expenseChange polythiourea in the application of preparing in antineoplastic and antiviral or antibacterials.
Background technology
Polymer is widely used in biological medicine, particularly in medicament as pharmaceutic adjuvant,Give medicine with effects such as certain formulations, but most polymers itself do not have biologically active. WillThere is bioactive molecule as monomer polymerization, can obtain thering is bioactive polymer. As,(the Tangetal.Curcuminpolymersasanticancerconjugates. such as Shen YouqingBiomaterials31,7139-49 (2010)) with the traditional Chinese medicine ingredients curcumin conduct with antitumor activityOne of monomer, has prepared the curcumin polymer with anti-tumor capacity.
Thiourea (TUs) refer to and in molecular structure, there is thiourea group (NH-CS-NH-,TU) a compounds. Many have the micromolecular compound that contains thiourea group and have goodBiologically active, as antibacterial, the sterilization of wide spectrum, the character such as antiviral (LiuJ, YangS, LiXetal.,SynthesisandantiviralbioactivityofchiralthioureascontainingleucineandPhosphonatemoieties.Molecules15,5112-5123 (2010)). Containing of another kind of complexityThe compound of thiourea group also have antitumor curative effect (ManjulaS, MalleshappaNoolviN,VipanPariharKetal.,Synthesisandantitumoractivityofopticallyactivethioureaandtheir2-aminobenzothiazolederivatives:AnovelclassofAnticanceragents.Eur.J.Med.Chem.44,2923-2929 (2009)), still, but thisA little compounds are all only containing a thiourea group, and water-soluble extreme difference, and they are still cell toxicant class chemical drugsThing, they are to realize antineoplastic ability by directly killing tumour cell.
The polymer that main chain or side chain contain multiple thiourea groups is polythiourea type polymer. Thiocarbamide polymerizationIt is less that thing is directly used in the report of disease treatment. The Chinese patent of issuing on December 18th, 1996A kind of water miscible sulfonic acid anion type aromatic series polythiourea is disclosed in CN1138323A, for havingDerivative recurring unit and the number-average molecular weight of 3～50 aromatic diamines that replaced by anionic group is littleThe oligomer of the polythiourea in 10,000. This polythiourea has resisting HIV activity, canBe directly used in treatment mankind's AIDS complexs relevant with AIDS (ARC). But the linear polythiourea of this classThe preparation process of molecule is extremely loaded down with trivial details, and the toxicity of the raw material adopting is extremely strong, and they workMechanism be that its anion and rigidity aromatic radical polymer backbone adhere to virus, not due to institute ownThe thiourea group having.
Sulfur-bearing urea polymers and hyperbranched macromolecular in the present invention, by reducing in neoplastic disease human body andExcess copper element in knurl, block tumor neovasculature generation and reach antitumous effect. CopperAt the necessary trace element of human body, normal human contains and is subject to strict control. But this human body of tumourCopper content is higher in interior copper and tumour, promoted the hyperplasia of tumour medium vessels and the infiltration of tumour growth andShift (Ishida, S., Andreux, P., Poitry-Yamate, C., Auwerx, J.&Hanahan, D.BioavailablecoppermodulatesoxidativephosphorylationandgrowthofTumors.Proc.Natl.Acad.Sci.USA110,19507-19512 (2013)). By reducing in bodyCopper, can suppress growth and transfer (Hassouneh, the B.etal. of tumourTetrathiomolybdatepromotestumornecrosisandpreventsdistantmetastasesbysuppressingangiogenesisinheadandneckcancer.Mol.CancerTher.6,1039-1045 (2007)). In the present invention can be by Cu containing thiocarbamide linearity and dissaving polymer2+AlsoOriginally be Cu+And complexing with it (Krzewska, S., Pajdowski, L.&H.Studiesonthereactionofcopper(II)withthiourea—II:Themodificationofbjerrum'smethod.ThedeterminationofequilibriuminsimultaneousredoxandComplexationreactions.J.Inorg.Nucl.Chem.42,87-88 (1980)), thereby reduce bodyInterior effectively copper concentration, stops the new Angiogenesis of tumour, plays antitumor and anti-transfer effect. Meanwhile,Thiourea group can reduce the superoxide radical ROS in tumour cell effectively, also plays antitumor action.Because this is not cell toxicant compound containing thiocarbamide linearity and dissaving polymer, there is no cytotoxicity,Thereby normal cell and tissue are not had to toxicity, toxic and side effect is few.
Summary of the invention
The invention provides the application of a kind of linear polythiourea and hyperbranched poly thiocarbamide. Containing the straight chain of thiocarbamideIn type and hyperbranched type polymer, contain a large amount of thiourea groups, tumor tissues is had to significant growth and press downMake use, normal cell is shown to very low cytotoxicity simultaneously, can be used for preparing antineoplastic;Also multiple bacterial strain is all had to good fungistatic effect, can be used for preparing antiviral or antibacterials.
Linear polythiourea is in an application of preparing in antitumor, antiviral and antibacterials, describedLinear polythiourea has suc as formula the structural formula shown in I:
In formula, R1、R2The alkyl that is 1～10 independently selected from hydrogen, carbon number, aromatic radical or containing N,The heteroatom group of O, S, the number-average molecular weight of described linear polythiourea is 50～50000.
As preferably, for the preparation of the application in antitumor, antiviral and antibacterials, described lineThe structural formula of shape polythiourea is selected from the one in following formula:
The preparation method of described linear polythiourea:
Under catalyst action, by containing the monomer of two isothiocyanate groups or thiocarbamide with contain two amidosMonomer is dissolved in organic solvent, under inert gas shielding, and after heating polycondensation reaction, more purified placeReason obtains described linear polythiourea.
The present invention also provides a kind of hyperbranched poly thiocarbamide in antitumor, the antiviral and antibacterials of preparationIn application, the preparation method of described hyperbranched poly thiocarbamide is: will be containing at least two isothiocyanic acid basesThe monomer of group or thiocarbamide with contain the monomer of at least two amidos and be dissolved in organic solvent, protect at inert gasProtect after lower polycondensation reaction, more purified processing obtains described hyperbranched poly thiocarbamide.
As preferably, the described monomer containing at least two isothiocyanate groups is thiocarbamide, succinyl twoIsothiocyanates, 4,4 '-methylene two (phenyl isothiocyanate) or Isosorbide-5-Nitrae-bis-sulphur isocyanates butane;
The described monomer containing at least two amidos is ethylenediamine, 2-hydroxyl-1,3-propane diamine, lysineOr three-(2-amido ethyl) amine.
Described catalyst is selected the conventional catalyst of this area polycondensation reaction, as p-methyl benzenesulfonic acid,One or more in camphorsulfonic acid etc.; By adjusting catalyst amount, can obtain different molecular weightAbove-mentioned polythiourea molecule.
Described organic solvent is selected the conventional organic solvent of this area polycondensation reaction, as dimethylSulfoxide (DMSO), DMF (DMF), DMA (DMAc),1-METHYLPYRROLIDONE (NMP) etc., preferably DMAc, NMP.
The described reaction time carries out preferably according to the difference of selected mode of heating.
Described purification process is purified according to the characteristic solvent deposition of the polythiourea molecule preparing, after generally adopting absolute ether to precipitate, then with a small amount of frozen water washing purifying.
Further preferably, the number-average molecular weight of described hyperbranched poly thiocarbamide is 200～200000, superThe repetitive of branching polythiourea is selected from formula II-1 or formula II-2:
Described linear or hyperbranched poly thiocarbamide molecule dissolves in by molecular structure or water insoluble solution,Water-fast polythiourea can connect hydrophilic polymer PEG can be water-soluble.
Described linear or hyperbranched thiocarbamide polymer is for the application of antineoplastic, its effective doseFor 1mg/kg is to their maximum permissible dosage (starting to show more highly toxic dosage);
The present invention also provides a kind of anti-tumor composition, with described linear polythiourea or over-expenseChange polythiourea as active component, be suitable for pharmacy the medicament that additives are prepared from. Described medicamentBy oral or intravenously administrable.
The present invention also provides a kind of bactericidal composition, with described linear polythiourea or hyperbranched poly sulphurUrea, as active component, is suitable for pharmacy the antimicrobial agent that additives are prepared from.
Compared with prior art, tool of the present invention has the following advantages:
The invention discloses the new purposes of a kind of linear polythiourea and hyperbranched poly thiocarbamide, through cell in vitroToxicity test shows, described linear polythiourea and hyperbranched poly thiocarbamide are to human tumor cell line or peopleThe equal no cytotoxicity of class normal cell strain; But anti-tumor in vivo experiment shows, described linear poly-sulphurUrea and hyperbranched poly thiocarbamide have significant growth inhibition effect to tumor tissues, especially to human lung adenocarcinomaCell (A549), human breast cancer cell (BCap-37), human mouth epidermoid carcinoma cell (KB),People's lung fibroblast (HFL1) and human bronchial epithelial cell (BEAS-2B) all show very lowCytotoxicity, there is good antitumous effect simultaneously.
If described linear polythiourea and hyperbranched poly thiocarbamide are water-soluble, can directly use, if dredgeWater-based, under conventional medicinal formula, has a significant restrained action to tumor tissues tool.
If described linear polythiourea and hyperbranched poly thiocarbamide are water-soluble, can directly use, if dredgeWater-based, under conventional medicinal formula, has inhibitory action to the microorganisms such as bacterium and viral growth.
Brief description of the drawings
Fig. 1 be preparation in embodiment 1 Pegylation containing the people large intestine of thiocarbamide linear polymer to nude miceThe tumor suppression design sketch of tumor model;
Fig. 2 be preparation in embodiment 2 Pegylation containing the National People's Congress of thiocarbamide dissaving polymer to nude miceThe tumor suppression design sketch of intestinal cancer tumor model;
Fig. 3 is the toxic effect figure of the polythiourea molecule prepared of embodiment 3 to normal cell and cancer cell;
Fig. 4 is gross tumor volume variation diagram in the vivo antitumor experiment of the polythiourea molecule prepared of embodiment 3, andWith PBS buffer solution as a comparison, lower same;
Fig. 5 is nude mice body weight variation diagram in the vivo antitumor experiment of the polythiourea molecule prepared of embodiment 3;
Fig. 6 is the tumor weight stripping after the vivo antitumor experiment of the polythiourea molecule prepared of embodiment 3 finishesFigure.
Detailed description of the invention:
Embodiment 1 utilizes Isosorbide-5-Nitrae-bis-sulphur isocyanates butane and reacting ethylenediamine to prepare linear thiocarbamide polymerReaction equation is as follows:
By Isosorbide-5-Nitrae-bis-sulphur isocyanates butane (0.69g, 4mmol) and ethylenediamine (0.24g, 4mmol)Be mixed in 2mL carrene, at room temperature stir 24 hours. With after ether sedimentation 3 times, obtainColourless dope, productive rate 90%, number-average molecular weight is 14500.
By above-mentioned gained dope (0.7g) and PEG550-NH2(1g) be dissolved in the dichloromethane of 5mLAlkane. After reactant liquor at room temperature stirs and spends the night, use ether sedimentation 3 times, obtain containing of PegylationThiocarbamide linear polymer (1.0g).
With the synthetic Pegylation of embodiment 1 containing the human large intestine cancer of thiocarbamide linear polymer to nude miceTumor model carries out inhibition test in body, and control group and experimental group are set, every group of 7 tumor bearing nude mices,Each dosage is 50 μ mol thiourea group/kg, altogether administration 5 times. Before each administration, record nakedThe size of mouse tumour and the body weight of nude mice, concrete outcome respectively as shown in Figure 1. Wherein, tumour bodyLong-pending by following formula calculating:
Gross tumor volume=length x width x width/2;
As can be seen from Figure 1: this Pegylation containing the growth of thiocarbamide linear polymer to tumor tissuesAlso there is good inhibition ability. Experimental group all has extremely remarkable with control group aspect gross tumor volumeDifference. This Pegylation containing thiocarbamide linear polymer to nude mice without general toxicity.
Embodiment 2 utilizes Isosorbide-5-Nitrae-bis-sulphur isocyanates butane and three-(2-amido ethyl) amine to react and prepare sulfur-bearingUrea dissaving polymer
Reaction equation is as follows:
By Isosorbide-5-Nitrae-bis-sulphur isocyanates butane (0.69g, 4mmol) and three-(2-amido ethyl) amine (0.58g,4mmol) be mixed in 3mL carrene, at room temperature stir 24 hours. With ether sedimentation 3 timesAfter, obtain colourless dope, productive rate 93%, number-average molecular weight is 4500.
PEG550-COOH (2g) is dissolved in after the carrene of 20mL, adds carbonyl dimidazoles(1g), under room temperature, stir after 15min, then add above-mentioned dope (0.5g). Reactant liquor is in room temperatureAfter lower stirring is spent the night, with ether sedimentation 3 times, obtain Pegylation containing thiocarbamide dissaving polymer(1.2g)。
With the synthetic Pegylation of embodiment 2 containing the people large intestine of thiocarbamide dissaving polymer to nude miceTumor model carries out inhibition test in body, and control group and experimental group are set, every group of 7 tumor bearing nude mices,Each dosage is 50mg/kg, altogether administration 5 times. Before each administration, record the large of nude mice tumourThe body weight of little and nude mice, concrete outcome respectively as shown in Figure 2. As can be seen from Figure 2: this polythioureaDissaving polymer also has good inhibition ability to the growth of tumor tissues. Experimental group is at tumour bodyLong-pending aspect all has extremely significant difference with control group. This polythiourea dissaving polymer to nude mice alsoWithout general toxicity.
Embodiment 3 utilizes thiocarbamide molecule and 2-hydroxyl-1, the linear thiocarbamide polymer of 3-propane diamine reaction preparationReaction equation is as follows:
1.0000g thiocarbamide, 1.1839g1,3-diaminourea-2-hydroxy propane and 20mg p-methyl benzenesulfonic acid are dissolved inIn 5mLNMP, under argon shield, spend the night 160 DEG C of reactions, after product precipitates with absolute ether,With a small amount of frozen water washing, obtain the end product shown in 1.35g formula I again, productive rate 76%, number is divided equallySon amount is 5000～6000.
1H-NMR(400MHz,DMSO):δ(ppm)7.76(s,2H),5.13(d,J＝3.1Hz,1H),3.89(d,J＝3.2Hz,1H),3.16(d,J＝11.8Hz,2H),2.92(d,J＝12.0Hz,2H)。
The polythiourea molecule (being called for short L-PTU) of preparing taking embodiment 3 is example, utilizes this area generalDetection cell survival and MTT (3-(4,5-dimethylthiazole-2)-2,5-diphenyl four nitrogen of growthAzoles bromine salt) method detect L-PTU to human lung adenocarcinoma cell (A549), human breast cancer cell (BCap-37),Human mouth epidermoid carcinoma cell (KB), people's lung fibroblast (HFL1), human bronchial epithelial are thinBorn of the same parents' (BEAS-2B) cytotoxicity. Concrete outcome as shown in Figure 3.
Wherein, the detection principle of mtt assay is: outside the Intramitochondrial succinate dehydrogenase of living cells can makeProperty MTT in source is reduced to water-insoluble bluish violet crystallization first a ceremonial jade-ladle, used in libation (Forman) and is deposited in cell,And dead cell is without this function. The first a ceremonial jade-ladle, used in libation of DMSO in can dissolved cell, surveys with enzyme-linked immunosorbent assay instrumentFixed its absorbance value, can reflect living cells quantity indirectly. Within the scope of certain cell number, MTT knotThe brilliant amount forming is directly proportional to cell number.
Taking BCap-37 cell as example. The BCap-37 cell of taking the logarithm growth period, with 0.25% pancreas eggAfter white enzymic digestion, then with containing 10% calf serum, 100U/mL penicillin and streptomysinRPMI-1640 nutrient solution is diluted to 4.5 × 107The single cell suspension of individual/L concentration, is inoculated in 96Orifice plate, every hole 100 μ L,, establish 6 multiple holes for every group by totally 9 groups. Cultivate after 24 hours and change and cultivateBase, each hole adds the L-PTU nutrient solution of variable concentrations. After dosing 48 hours, add containing MTTRPMI-1640 nutrient solution 100 μ L, continue cultivate 3 hours. Centrifugal abandoning after supernatant, every hole adds100 μ LDMSO, vibration is dissolved, and measuring when measuring wavelength with enzyme linked immunosorbent assay is 562nm, reference wavelengthThe absorbance in every hole (A) during for 620nm. Calculate cell survival rate by following formula:
Cell survival rate=(experimental group A value/blank group A value) × 100%.
As can be seen from Figure 3: L-PTU is to A549 cell, BCap-37 cell, KB cell, HFL1Cell, the equal no cytotoxicity of BEAS-2B cell. This shows that L-PTU overall safety is nontoxic. At noteAfter injecting in body, even if L-PTU spreads other normal structures of entering in cyclic process in vivo, alsoCan not cause damage by normal tissue.
In the tumor bearing nude mice in vivo studies of example, control group is set at the polymer synthetic taking embodiment 3And experimental group, every group of 6 tumor bearing nude mices, each dosage is 50 μ mol thiourea group/kg, altogetherAdministration 5 times. Before each administration, record the size of nude mice tumour and the body weight of nude mice, concrete outcomeRespectively as shown in Figure 3 and Figure 4. Administration finished after 4 days, put to death nude mice according to animal Ethical Demand,Strip tumour, take weight, result as shown in Figure 6.
Can find out from Fig. 4 and Fig. 6: L-PTU has good inhibition ability to the growth of tumor tissues.Experimental group all has extremely significant difference with control group aspect gross tumor volume or tumor weight. FromFig. 5 can find out: L-PTU to nude mice without general toxicity.
Optimal antineoplastic should be a kind of without any cytotoxicity or only to tumour cell toolThere is cytotoxicity, but medicine that but can fine inhibition tumor growth. Consider above-mentioned L-PTU coupleThe equal no cytotoxicity of normal cell or tumour cell, but show the inhibition good to tumor growthAbility, this shows that polythiourea molecule of the present invention has great potentiality as cancer therapy drug.
Anti-microbial property test:
With the synthetic Pegylation of embodiment 1 containing thiocarbamide linear polymer (be called for short L-PPTU),The synthetic Pegylation of embodiment 2 containing thiocarbamide dissaving polymer (being called for short B-PPTU), implementPolythiourea molecule L-PTU prepared by example 3 is example, measures it to staphylococcus aureus(Staphylococcusaureus), enterococcus faecalis (Enterococcusfaecalis), Escherichia coli(Escherichiacoli), MRSE (Staphylococcusepidermidis), aerogenesis intestinesThe bacterium such as bacillus (Enterobactercloacae) and proteus vulgaris (Proteusvalgaris)The minimum inhibitory concentration (MIC) of strain.
Get frozenly in the bacterial strain to be measured of-20 DEG C, streak inoculation is in M-H agar plate, 37 DEG C of incubatorsMiddle overnight incubation, inferior daily oese picking monoclonal bacterium colony, is inoculated in 3mL nutrient broth,37 DEG C, 220r/min, rises in value to logarithmic growth after date, bacterium liquid is diluted to 0.5 Maxwell with M-H meat soupThan turbid standard. Then for subsequent use after above-mentioned bacteria suspension 1:100 being diluted with M-H meat soup. After dilutionBacterium liquid should be inoculated in 15min. L-PPTU, B-PPTU and L-PTU are diluted with sterilized waterBecome 200mg/mL, filtration sterilization, packing is for subsequent use. Gentamicin and amikacin are blue as leather respectivelyThe positive control of family name's negative bacterium and gram-positive bacteria. Get 60 holes, the aseptic 96 non-edge of orifice plate, every holeAdd respectively 100 μ LM-H meat soups, every row adds successively according to flag sequence in the 1st row hole100 μ LL-PPTU, B-PPTU, L-PTU, antibiotic, M-H meat soup. Fully mix with the volley of rifle fireAfter, join the 2nd corresponding hole from every hole sucking-off 100 μ L, the like, 2 doubling dilutions are extremelyThe 10th is listed as, and discards 100 μ L liquid of last sucking-off. Then every hole adds the above-mentioned preparation of 100 μ LBacteria suspension to be measured to make the whole bacterial concentration of every Kongzui be 5 × 105CFU/mL. In the periphery of 96 orifice plates,Add 200 μ L bacteria suspension to be measured (not containing medicine) as aseptic contrast. Get bacteria suspension to be measured exists simultaneouslyAgar plate is uploaded culture, to examine bacteria-checking liquid purity. 96 orifice plates of having inoculated are vibrated at traceOn device, shake 1min, fully mix and be placed in wet box, in 37 DEG C of incubators, hatch 24h. With naked eyesObserve the lowest concentration of drug MIC of medicine for this reason in limpid hole, should check the thin of growth control hole simultaneouslyWhether bacteria growing situation is good, and whether aseptic control wells is limpid, checks that the flat board of bacteria suspension is cultivated situationTo determine whether it pollutes, whether the MIC value of Quality Control bacterial strain is in Quality Control scope. This measures and repeats 3Inferior.
Table 1
Note:*Gentamicin,**Amikacin
Table 1 be the synthetic Pegylation of embodiment 1 containing thiocarbamide linear polymer L-PPTU, enforcementPreparing containing thiocarbamide dissaving polymer B-PPTU, embodiment 3 of the synthetic Pegylation of example 2Polythiourea molecule L-PTU is minimum antibacterial dense to common Gram-negative bacteria and gram-positive bacteriaDegree. As can be seen from Table 1, all kinds of sulfur-bearing urea polymers are the growth of anti-bacteria preferably all, itsMIC value is all positioned at 25～100 μ g/mL. It is blue that its fungistatic effect for gram-positive bacteria is better than leatherFamily name's negative bacterium.
Claims (10)
1. the application of linear polythiourea in antitumor, the antiviral and antibacterials of preparation, itsBe characterised in that, described linear polythiourea has suc as formula the structural formula shown in I:
In formula, R1、R2The alkyl that is 1～10 independently selected from hydrogen, carbon number, aromatic radical or containing N,The heteroatom group of O, S, the number-average molecular weight of described linear polythiourea is 50～50000.
2. linear polythiourea according to claim 1 is antitumor, antiviral and antibacterial in preparationApplication in medicine, is characterized in that, the structural formula of described linear polythiourea is selected from following formulaA kind of:
3. linear polythiourea according to claim 1 is antitumor, antiviral and anti-in preparationApplication in bacterium medicine, is characterized in that, the antitumor dosage of described linear polythiourea is 1mg/kgTo its maximum tolerated dose.
4. the application of hyperbranched poly thiocarbamide in antitumor, the antiviral and antibacterials of preparation,It is characterized in that, the preparation method of described hyperbranched poly thiocarbamide is: will be containing at least two different sulphur cyanogenThe monomer of acid groups or thiocarbamide and be dissolved in organic solvent containing the monomer of at least two amidos, in inertiaUnder gas shield, after heating polycondensation reaction, more purified processing obtains described hyperbranched poly thiocarbamide.
5. hyperbranched poly thiocarbamide according to claim 4 is antitumor, antiviral and anti-in preparationApplication in bacterium medicine, is characterized in that, the described list containing at least two isothiocyanates groupsBody is the different sulfo-cyano group of Isosorbide-5-Nitrae-bis-butyl ester, succinyl diisothio-cyanate, 4,4 '-methylene two (different sulphurPhenyl-cyanate) or Isosorbide-5-Nitrae-bis-sulphur isocyanates butane;
The described monomer containing at least two amidos is ethylenediamine, 2-hydroxyl-1,3-propane diamine, lysineOr three-(2-amido ethyl) amine.
6. hyperbranched poly thiocarbamide according to claim 5 is antitumor, antiviral and anti-in preparationApplication in bacterium medicine, is characterized in that, the number-average molecular weight of described hyperbranched poly thiocarbamide is200～200000, the repetitive of hyperbranched poly thiocarbamide is selected from formula II-1 or formula II-2:
7. hyperbranched poly thiocarbamide according to claim 4 is antitumor, antiviral and anti-in preparationApplication in bacterium medicine, is characterized in that, the antitumor dosage of described hyperbranched poly thiocarbamide is 1mg/kgTo its maximum tolerated dose.
8. an anti-tumor composition, is characterized in that, with described linear polythiourea or superBranching polythiourea, as active component, is suitable for pharmacy the medicament that additives are prepared from.
9. anti-tumor composition according to claim 8, is characterized in that, describedMedicament is by oral or intravenously administrable.
10. a bactericidal composition, is characterized in that, with described linear polythiourea or hyperbranchedPolythiourea, as active component, is suitable for pharmacy the antimicrobial agent that additives are prepared from.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017047733A1 (en) * | 2015-09-16 | 2017-03-23 | 国立大学法人東京大学 | Novel underwater adhesive compound |
| CN110551274A (en) * | 2019-08-06 | 2019-12-10 | 中山大学 | Intrinsic self-repairing and recyclable polythiourea polymer and preparation method and application thereof |
| WO2021230241A1 (en) * | 2020-05-11 | 2021-11-18 | 国立大学法人 東京大学 | Self-healing polymer material |
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| CN1138323A (en) * | 1994-01-03 | 1996-12-18 | 默里尔药物公司 | Pharmaceutical formulations comprising polythiourea and method of use thereof |
| JP2010114122A (en) * | 2008-11-04 | 2010-05-20 | Konica Minolta Medical & Graphic Inc | Organic piezoelectric body, ultrasonic resonator, ultrasonic probe and ultrasonic image detector |
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| CN1138323A (en) * | 1994-01-03 | 1996-12-18 | 默里尔药物公司 | Pharmaceutical formulations comprising polythiourea and method of use thereof |
| JP2010114122A (en) * | 2008-11-04 | 2010-05-20 | Konica Minolta Medical & Graphic Inc | Organic piezoelectric body, ultrasonic resonator, ultrasonic probe and ultrasonic image detector |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017047733A1 (en) * | 2015-09-16 | 2017-03-23 | 国立大学法人東京大学 | Novel underwater adhesive compound |
| JPWO2017047733A1 (en) * | 2015-09-16 | 2018-08-09 | 国立大学法人 東京大学 | New underwater adhesive compound |
| CN110551274A (en) * | 2019-08-06 | 2019-12-10 | 中山大学 | Intrinsic self-repairing and recyclable polythiourea polymer and preparation method and application thereof |
| CN110551274B (en) * | 2019-08-06 | 2020-06-16 | 中山大学 | Intrinsic self-repairing and recyclable polythiourea polymer and preparation method and application thereof |
| WO2021230241A1 (en) * | 2020-05-11 | 2021-11-18 | 国立大学法人 東京大学 | Self-healing polymer material |
| JP7468932B2 (en) | 2020-05-11 | 2024-04-16 | 国立大学法人 東京大学 | Self-healing polymer materials |
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