- Self-assembled micelles from an amphiphilic hyperbranched copolymer with polyphosphate arms for drug delivery
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A novel type of amphiphilic hyperbranched multiarm copolymer [H40-star-(PLA-b-PEP-OH)] was synthesized through a two-step ring-opening polymerization (ROP) procedure and applied to drug delivery. First, Boltorn H40 was used as macroinitiator for the ROP of l-lactide to form the intermediate (H40-star-PLA-OH). Then, the ROP of ethyl ethylene phosphate was further initiated to produce H40-star-(PLA-b-PEP-OH). The resulting hyperbranched multiarm copolymers were characterized by 1H, 13C, and 31P NMR, GPC, and FTIR spectra. Benefiting from the amphiphilic structure, H40-star-(PLA-b-PEP-OH) was able to self-assemble into micelles in water with an average diameter of 130 nm. In vitro evaluation of these micelles demonstrated their excellent biocompatibility and efficient cellular uptake by methyl tetrazolium assay, flow cytometry, and confocal laser scanning microscopy measurements. Doxorubicin-loaded micelles were investigated for the proliferation inhibition of a Hela human cervical carcinoma cell line, and the Doxorubicin dose required for 50% cellular growth inhibition was found to be 1 μg/mL. These results indicate that H40-star-(PLA-b-PEP-OH) micelles can be used as safe, promising drug-delivery systems.
- Liu, Jinyao,Huang, Wei,Pang, Yan,Zhu, Xinyuan,Zhou, Yongfeng,Yan, Deyue
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- Synthesis and ring-opening polymerization of glycidyl ethylene phosphate with a formation of linear and branched polyphosphates
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Newly obtained cyclic monomer, glycidyl ethylene phosphate, readily forms branched or linear polymers via ring-opening polymerization catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene or by [(BHT)Mg(OBn)(THF)]2, respectively. The polymers obtained are promising for biomedical applications.
- Nifant'ev, Ilya E.,Shlyakhtin, Andrey V.,Bagrov, Vladimir V.,Komarov, Pavel D.,Kosarev, Maxim A.,Tavtorkin, Alexander N.,Minyaev, Mikhail E.,Roznyatovsky, Vitaly A.,Ivchenko, Pavel V.
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- Synthesis and micellization of amphiphilic biodegradable methoxypolyethylene glycol/poly(d,l-lactide)/polyphosphate block copolymer
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A new amphiphilic biodegradable methoxypolyethylene glycol/poly(d,l- lactide)/poly(ethyl ethylene phosphate) (MPEG-b-PLA-b-PEEP) block copolymer was synthesized by ring-opening polymerization of ethyl ethylene phosphate (EEP) with methoxypolyethylene glycol/poly(d,l-lactide) (MPEG-b-PLA) as a macroinitiator, which was prepared by ring-opening polymerization of d,l-lactide (LA) initiated by methoxypolyethylene glycol (MPEG) using stannous octoate as catalyst. The structures of the block copolymers were confirmed by IR, 1H NMR and GPC analysis. Fluorescence measurements were applied to determine the critical micelle concentration (CMC) of the copolymer micelle solutions. The diameter and the distribution of micelles were characterized by dynamic light scattering (DLS) and the shape was perceived using transmission electron microscopy (TEM). The results prove that the copolymers can self-assemble into nano-micelles in aqueous solutions. The CMC of the copolymer solutions increased and the size of the micelles reduced with increasing of the proportion of PEEP segments. TEM images demonstrate that all micelles are spherical.
- Wu, Qiuhua,Wang, Chuang,Zhang, Dan,Song, Ximing,Verpoort, Francis,Zhang, Guolin
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- Breathing air as oxidant: Optimization of 2-chloro-2-oxo-1,3,2-dioxaphospholane synthesis as a precursor for phosphoryl choline derivatives and cyclic phosphate monomers
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Phosphoryl choline derivatives are important compounds for drug development. Also other phosphoesters have received increased demand in recent years. Many of such compounds rely 2-chloro-2-oxo-1,3,2-dioxaphospholane (COP) as an intermediate. COP is available in a two-step reaction from the cyclic adduct of phosphorus chloride and ethylene glycol after oxidation. Although commercially available, in-house synthesis of COP is often required due to pricing, purity, and delivery issues. Air is a convenient and economical oxidizing agent, yet not used for synthesis of COP. While slow consumption of the P(III)-precursor 2-chloro-1,3,2-dioxaphospholane with molecular oxygen from a gas bottle, high amounts of unreacted oxygen are lavished and even may cause an explosion. Oxygen from air is a reasonable and safer alternative. Additionally, catalytic amounts of cobalt(II)chloride increase the reaction kinetics remarkably. The results presented allow a controlled and fast access to a variety of phosphoesters by optimized reaction conditions of COP and its derivatives.
- Becker, Greta,Wurm, Frederik R.
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- Biomimetic Honeycomb-Structured Surfaces Formed from Block Copolymers Incorporating Acryloyl Phosphorylcholine
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We report the preparation of biomimetic honeycomb-structured porous films. These regular arrays were obtained by casting block copolymers composed of polystyrene and poly(acryloyl phosphorylcholine), so that they mimicked a cell membrane. The size of the pores and regularity of the hexagonal array is strongly dependent on the block length. The block copolymers were prepared via RAFT (reversible addition fragmentation transfer) polymerization leading to well-defined products with a good control over block sizes.
- Stenzel, Martina H.,Davis, Thomas P.
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- Interaction between zwitterionic surfactants and amphiphilic drug: A tensiometric study
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The physicochemical properties, viz, critical micelle concentration (cmc), surface excess concentration (Γmax), minimum area per head group (Amin) of zwitterionic surfactants (designated as n(-)-2-m(+); n = 8, 10, 12 and m = 12, 14, 16) and their mixtures with amphiphilic antidepressant drug amitriptyline hydrochloride (AMT) were determined by using surface tension measurements. The cmc and ideal cmc (cmcid) values along with interaction parameters, βm and β α (calculated using Rubingh's and Rosen's models), suggest attractive interactions among the components. The Krafft temperature measurements also indicate strong attractive interactions. Γmax (or Amin) increases (or decreases) with the addition of gemini surfactant; the values being closer to that of the drug. These values and micellar mole fraction (Xm-calculated from Rubingh's model and X 1Moto-calculated from Motomura's model) indicate larger contribution of gemini surfactants in mixed micelles and smaller contribution at air/solution interface (as mole fraction values at interface, X σ1, are slightly smaller than X1m). The standard Gibbs energy of micellization (ΔG°mic) and adsorption (ΔG°ad) as well as excess energy of mixing (ΔGexm) are all negative. All these results suggest higher stability of the mixed systems. UV absorbance results also suggest that the mixed micelles are stable for several days. by Oldenbourg Wissenschaftsverlag.
- Ansari, Wajid H.,Noori, Sahar,Naqvi, Andleeb Z.,Kabir-Ud-Din
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- Effect of Asymmetric Dimeric Zwitterionic Surfactants on Micellization Behavior of Amphiphilic Drugs
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Abstract The micellization process in mixtures of amphiphilic drugs and asymmetric dimeric zwitterionic surfactants have been investigated tensiometrically. The drugs used are from two families: imipramine hydrochloride (IMP) - a tricyclic antidepressant and ibuprofen (IBF) - a nonsteroidal antiinflammatory drug, whereas zwitterionic dimeric surfactants are heterogemini surfactants that contain quaternary ammonium and phosphate groups as heads. The results show that the cmc of drug-surfactant mixtures decreases with the increase in stoichiometric mole fraction of surfactants (α 1), suggesting attractive interaction among the two components. This is supported by the values of cmc id (critical micelle concentration values for ideal mixing) which are always greater than experimental cmc values. Also, the decrease in magnitude is more in IBF-dimeric surfactant mixed systems than in IMP-dimeric surfactant mixed systems. Micellar mole fraction values, obtained using Rubingh's (Formula presented.) and Motomura's (Formula presented.) models, are lower than the micellar mole fraction for ideal mixing (Formula presented.). The micellar interaction parameter (βm) follows the order: 8(-)-2-16(+) > 10(-)-2-16(+) > 10(-)-2-14(+) > 8(-)-2-14(+). The results are explained on the basis of difference in tail lengths. Interfacial mole fraction (Formula presented.) values, evaluated using Rosen's model, are higher than (Formula presented.) values for IMP-10(-)-2-16(+) and IMP-10(-)-2-14(+) systems while for all other systems (except 8(-)-2-14(+)) the values are smaller than (Formula presented.). The interaction parameter at the interface (βσ) is negative and (Formula presented.) values are greater than (Formula presented.) in magnitude. All the results indicate that the dimeric surfactants are mostly in cationic form.
- Noori, Sahar,Naqvi, Andleeb Z.,Ansari, Wajid H.,Kabir-Ud-Din
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- Preparation method of cyclic chlorinated phosphate
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The present invention relates to a cyclic chlorinated phosphate preparation method, wherein phosphorus oxychloride and alkyl siloxane are subjected to a cyclization reaction in the presence of an aprotic solvent to prepare cyclic chlorinated phosphate, the structural formula of alkyl siloxane is shown in the specification, the structural formula of the cyclic chlorinated phosphate is shown in thespecification, and n is a number between 1 and 5. According to the invention, synthesis is a one-step reaction, the reaction avoids an oxidation reaction (the oxidation reaction is a high-risk process), and the method is high in reaction selectivity and yield, few in reaction steps and suitable for industrial production.
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Paragraph 0025-0039
(2021/01/29)
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- Five-membered ring phosphate compound, and preparation method and application thereof
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The invention belongs to the technical field of flame retardance, and especially relates to a five-membered ring phosphate compound. The structural general formula of the five-membered ring phosphatecompound is represented by formula 1 shown in the description; and in the formula, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R and R are independently selected from hydrogen, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkynyloxy group, an enyloxy group, a silyl group, a siloxane group, aryl silicon, an arylsilyl group, an arylsiloxy group, a halogenated phenyl group, a halogenated biphenyl group, a phenolic group, an alkyl-containing phenolic group, an alkenyl-containing phenolic group, an alkynyl-containing phenolic group, a nitrile-containing phenolic group, a monohalogenated phenolic group and a polyhalogenated phenolic group. The five-membered ring phosphate compound provided by the invention has excellent flame retardancy, can effectively prevent electrolytes from being oxidized when being applied to the field of batteries, reduces oxygenolysis of the electrolytes on positive electrodes, and remarkably improves the comprehensive properties of high temperature, circulation, storage and the like of the batteries.
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Paragraph 0091-0095
(2020/06/17)
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- Flame-retardant additive, preparation method therefor and application of flame-retardant additive
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The invention discloses a flame-retardant additive, a preparation method therefor and an application of the flame-retardant additive. In view of that phosphorus-containing flame retardants in the prior art have many performance disadvantages and the problem of high manufacturing and service costs, the invention provides a novel phosphorus-containing flame retardant. The flame retardant is used asa flame-retardant additive in an electrolyte of a non-aqueous electrolytte secondary battery. The invention simultaneously provides the preparation method for the flame retardant. The phosphorus-containing flame retardant prepared by the method not only can effectively improve safety of batteries, but also has a specific positive-negative pole membrane forming function, and thus, comprehensive properties such as high-/low-temperature, cycling and storage properties of the secondary battery can be remarkably improved. The preparation method for the flame retardant, provided by the invention, has the advantages that the raw material cost is low, the preparation process is simple in step, the operation is safe, the product purity is high, and the environmental pollution is light.
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Paragraph 0053-0062
(2020/01/03)
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- Preparation method 2 -chloro -2 - oxo -1, 3, 2 - dioxaphospholane (by machine translation)
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The invention discloses 2 - chlorine -2 - oxo -1, and discloses a preparation method thereof. The method. 3, 2 -dioxaphospholane. The preparation method comprises the following steps: in a solvent and a fluorine-containing solvent, 2 - chlorine -1, 3, 2 - dioxaphospholane and oxygen are subjected to an oxidation reaction as shown in the following manner. By introducing the fluorine-containing solvent into the reaction system 2 - chlorine -2 - oxo -1, 3, 2 - dioxolane, the reaction can be carried out at normal temperature and normal pressure, operation is simple, and reaction time is shortened, and the reaction time is shortened. The reaction yield, the product purity is high, the product purity is high, the fluorine-containing solvent can be separated, the fluorine-containing solvent can be recycled, and the high yield, the solvent can be recycled after being used repeatedly . the method is a low-cost, green chemical reaction, and has the potential. (by machine translation)
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Paragraph 0042-0060
(2019/08/20)
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- Synthesis of pillar[5]arenes with a PH-containing fragment
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The reactions of phosphorus(III) chloride and 2-chloro-1,3,2-dioxaphospholane with monohydroxypillar[5]arene afforded for the first time the corresponding PH-phosphonates. It was found that the newly formed P–O(Ar) bond is characterized by considerably reduced reactivity, which was rationalized by essential shielding of the phosphorus atom by the pillar[5]arene macrocycle. The pillar[5]arene scaffold stabilizes the highly reactive PIII–Cl fragment, so that the formation of macrocyclic dichlorophosphite can be detected under normal conditions.
- Nazarova,Makhmutova,Stoikov
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p. 1941 - 1945
(2017/10/27)
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- Preparation and application of reducing sensitive nano-micelle
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The invention relates to preparation and application of a reducing sensitive nano-micelle, belonging to preparation and application of an amphiphilic block polymer. A hydrophilic section and a hydrophobic section of the amphiphilic block polymer are connected with each other by a reducing responsive sulfur-sulfur bond; the nano-micelle is formed by self-assembling; the reducing sensitive nano-micelle consists of a shell and an inner core, wherein the shell is a hydrophilic polymer, and the inner core is a hydrophobic polymer; the hydrophilic section of the amphiphilic block polymer is polyphosphate, the hydrophobic section of the amphiphilic block polymer is poly(benzyl glutamate), and the hydrophilic section and the hydrophobic section of the amphiphilic block polymer are connected with each other by the reducing responsive sulfur-sulfur bond. The reducing sensitive nano-micelle has the advantages that the drug-loaded nano-micelle is difficult to dissociate outside the cells or in the blood, so that the drug encapsulated in the nano-micelle is enabled to be stable; once the nano-micelle enters the cancer cell, the sulfur-sulfur bond can be disconnected by glutathione which is a reducing matter in the cell, so that the nano-micelle is rapidly dissociated, the anti-cancer drug encapsulated in the nano-micelle can be rapidly and effectively released out, and an effective treatment effect is achieved; the reducing sensitive nano-micelle overcomes the defects that the drug is easy to leak in vivo, low in transport efficiency, slow in intracellular release speed, and the like.
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Paragraph 0032; 0064; 0067
(2017/07/19)
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- BLOCK COPOLYMER, LIQUID COMPOSITE THEREOF, NUCLEIC ACID PREPARATION, PREPARATION METHODS THEREFOR, AND USE THEREOF
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Provided are a polycaprolactone-polyphosphate block copolymer, a liquid composite formed by the block copolymer, a nucleic acid preparation, preparation methods for the copolymer and the liquid composite, and the use of the copolymer and the liquid composite in a nucleic acid medicine delivery system. The block copolymer prepared using the present invention has good biocompatibility, low cytotoxicity, and good biodegradability. The micelles provided in the present invention self-assemble into nano-particles in an aqueous solution, and have good stability, biocompatibility, and biodegradability, and low cytotoxicity. The preparation method is simple, has high repeatability, as a vector can protect small nucleic acids such as siRNA from biodegradation, can combine with the scale effect of nano-particles, and can be used for treating different diseases. Additionally, bonding targeting groups enable specificity recognition of different cancer cells.
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Paragraph 0093
(2015/04/15)
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- Multifunctional poly(phosphoester)s with two orthogonal protective groups
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A novel cyclic phosphate monomer, 2-(2-(benzyloxy)ethoxy)-1,3,2-dioxaphospholane-2-oxide (BnEEP), was developed to generate poly(phosphoester)s containing protected pendant hydroxyl groups by anionic ring-opening polymerization. The hydroxyl-groups were released by a mild catalytic hydrogenation leaving the polymer backbone intact. In addition, the number of pendant hydroxyl groups was varied by copolymerization of BnEEP with ethyl ethylene phosphate (EEP). Furthermore, copolymers of BnEEP with an acetal protected cyclic phosphate, 2-(2,2-dimethyl-1,3-dioxolan-4-yl-methoxy)-2-oxo-1,3,2-dioxaphospholane (GEP), were prepared in order to establish a selective deprotection of the acetal or the benzyl protective groups by acidic hydrolysis or catalytic hydrogenation respectively. No degradation of the polyester backbone was detected under the reported conditions. The novel monomer allows adjustment of the chemical and physical properties of the poly(phosphoester)s and gives access to various side chain functionalities.
- Müller, Laura K.,Steinbach, Tobias,Wurm, Frederik R.
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p. 42881 - 42888
(2015/05/27)
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- Synthesis and self-assembly of thermoresponsive amphiphilic biodegradable polypeptide/poly(ethyl ethylene phosphate) block copolymers
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We report the design and synthesis of new fully biodegradable thermoresponsive amphiphilic poly(γ-benzyl L-glutamate)/poly(ethyl ethylene phosphate) (PBLG-b-PEEP) block copolymers by ring-opening polymerization of N-carboxy-γ-benzyl L-glutamate anhydride (BLG-NCA) with amine-terminated poly(ethyl ethylene phosphate) (H2N-PEEP) as a macroinitiator. The fluorescence technique demonstrated that the block copolymers could form micelles composed of a hydrophobic core and a hydrophilic shell in aqueous solution. The morphology of the micelles as determined by transmission electron microscopy (TEM) was spherical. The size and critical micelle concentration (CMC) values of the micelles showed a decreasing trend as the PBLG segment increased. However, UV/Vis measurements showed that these block copolymers exhibited a reproducible temperature-responsive behavior with a lower critical solution temperature (LCST) that could be tuned by the block composition and the concentration.
- Wu, Qiuhua,Zhou, Dan,Kang, Renyu,Tang, Xiuping,Yang, Qi,Song, Ximing,Zhang, Guolin
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p. 2850 - 2858
(2015/02/19)
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- THE PREPARTION AND THE USE OF ETHOXY COMBRETASTATINS AND THEIR PRODRUGS
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The invention disclosed a total synthesis process of novel ethoxy combretastatins and their prodrugs. Combretastatins are chemically modified by ethoxy substituted on the 4'-position of their B aryl ring and are converted to be their soluble prodrugs of phosphate or their inner salt of phosphorylcholine by modifying the hydroxyl on the 3'-position of their B aryl ring. Similarly, 3'-amino combretastatin is 4'-ethoxy chemically modified and further side chain of amino acid can be introduced to the amino to form soluble prodrug of amino acidamide. The structure of the said compound is showed as formula (I). Ethoxy combretastatins possess potent tubulin polymerization inhibitory activity and can be used for the treatment of inhibiting tumor or neovascular.
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Page/Page column 13
(2009/06/27)
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- PREPARATION AND THE USE OF ETHOXY COMBRETASTATINS AND THEIR PRODRUGS
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The invention disclosed a total synthesis process of novel ethoxy combretastatins and their prodrugs. Combretastatins are chemically modified by ethoxy substituted on the 4′-position of their B aryl ring and are converted to be their soluble prodrugs of phosphate or their inner salt of phosphorylcholine by modifying the hydroxyl on the 3′-position of their B aryl ring. Similarly, 3′-amino combretastatin is 4′-ethoxy chemically modified and further side chain of amino acid can be introduced to the amino to form soluble prodrug of amino acidamide. The structure of the said compound is showed as formula (I). Ethoxy combretastatins possess potent tubulin polymerization inhibitory activity and can be used for the treatment of inhibiting tumor or neovascular.
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Page/Page column 9
(2009/07/17)
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- Phosphate based biodegradable polymers
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Featured are biodegradable polymers comprising repeat units derived from cyclic phosphate monomers and optionally further comprising repeat units derived from lactide or caprolactone monomers. Also featured are methods for preparing the biodegradable polymers of the invention and biodegradable polymer compositions comprising a biologically active substance and a biodegradable polymer. Additionally featured are articles and microspheres prepared from biodegradable polymers and polymer compositions of the invention. Further, methods for the controlled release of a biologically active substance using the biodegradable polymers of the invention are also described.
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- Fumaric acid derivative and polymer therefrom
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A polymer obtained by polymerizing a fumaric acid derivative represented by the following general formula (1): STR1 in which R1 represents an alkyl group having 1-6 carbon atoms and A denotes a radical of STR2 in which R2 and R3 represent each an alkyl group having 1-4 carbon atoms and may be identical with or different from each other, R4 denotes an alkyl group having 1-6 carbon atoms or a benzyl group and m and n denote each an integer of 1-6.
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- High yield synthesis of cyclic phosphites, phosphates, sulphites and sulphates of catechol and glycol mediated by hypervalent silicon centres
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Room temperature reactions of both tris(catecholato)silicate, M2[Si(o-C6H4O2)3] {M=Na, Et3NH} and glycolato silicate, K2[Si2(O2C2H4)5] with PCl3, POCl3, SOCl2 and SO2Cl2 proceed exothermally and afford easy isolation of the corresponding cyclic derivatives of catechol/glycol (1-8) in high yield, exemplifying the merit of hypervalent silicon centres in synthesis. (Et3NH)2[Si(o-C6H4O2)3] afford near quantitative conversions.
- Kingston,Sudheendra Rao
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p. 4841 - 4844
(2007/10/03)
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- Process for preparing organophosphates useful for increasing the ocular haemo- and biocompatibility of synthetic polymers
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STR1 A process for treating suitable synthetic polymers comprising the steps of (a) where appropriate, activating the surface to be treated, and, if necessary, providing spacer groups thereon; and (b) treating the surface with a compound of formula (I), wherein Y' is an alkylene group optionally containing an aryl group, a poly(ethylene glycol) or a glycerol group; R may be the same or different and each is a straight or branched C1-4 alkyl group, n is from 1 to 4 and X is a group which reacts with functional groups of the polymer. Polymeric surfaces and materials thus produced and shaped articles containing such surfaces and materials.
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