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79 results about "Phosphoramides" patented technology

Amide derivatives of phosphoric acid such as compounds that include the phosphoric triamide (P(=O)(N)(N)(N)) structure.

Flame-retardant cyclic phosphamide eutectic electrolyte and preparation method and application thereof

The invention belongs to the technical field of battery electrolyte, and particularly relates to flame-retardant cyclic phosphamide eutectic electrolyte as well as a preparation method and application thereof. According to the invention, through reasonable molecular design, the flame-retardant cyclic phosphamide eutectic electrolyte is obtained. Through the design of the annular structure, a film is formed on the positive and negative electrode interface of the electrode in the battery operation process, so that the stability of the battery is improved. Phosphamide groups are introduced into the cyclic structure, hydroxyl radicals generated in the battery operation process are captured through phosphorus-oxygen bonds, and the chain reaction of combustion is blocked. Meanwhile, different designs of amino groups on phosphamide can achieve a self-cleaning effect, hydrofluoric acid and water generated in a battery circulation process are removed, and the battery is protected from electrode structure collapse caused by the hydrofluoric acid and the water in an operation process. The safety performance of the lithium battery in the cycle process is obviously improved, and the development of the lithium battery with high safety and stable operation is effectively promoted. The preparation process is simple, safe to operate, high in purity and suitable for industrialization.
Owner:GUANGDONG JUSHI CHEM CO LTD +2

Synthesis and application of 5-terminal phosphorothioation modified oligonucleotide

The invention relates to the technical field of biological medicines, and particularly discloses synthesis and application of oligonucleotide with a spacer group embedded between 5-terminal oxygen and thiophosphoric acid. The chemical modification strategy comprises the following steps: preparing a modified nucleotide phosphoramidite monomer in which a spacer group is embedded between O5'and thiophosphoric acid P (V); performing solid-phase synthesis on the modified nucleotide phosphoramidite monomer to construct a target oligonucleotide molecule; a spacer group is embedded between oxygen at the 5 '-terminal of the oligonucleotide and thiophosphoric acid P (V) to form a 5'-terminal thiophosphoric acid structure; as the terminal modified thiophosphoric acid belongs to a non-phosphatase substrate, the terminal modified thiophosphoric acid can resist exonuclease degradation and improve the biological activity of siRNA after being modified.
Owner:SUZHOU SHENGNUOWEI BIOTECH CO LTD

Method for detecting related substances of 5 '(E)-VPA phosphoramidite monomer

The invention discloses a method for detecting 5 '(E)-VPA phosphoramidite monomer related substances, and belongs to the technical field of liquid chromatography detection. Related substances comprise 5 '-(E)-VP-2'-OMe-A (Bz), 5 '(Z)-VPA, 5'-(E)-VP-2 '-OMe-A-CE-P and 5' (E)-VPA-OX, and chromatographic detection conditions comprise that the column temperature is 23-27 DEG C, a stationary phase of a chromatographic column is octadecyl bonded silica gel, a mobile phase A is an ammonium acetate solution, a mobile phase B is acetonitrile, gradient elution is performed, and the like. According to the method, four related substances in the 5 '(E)-VPA phosphoramidite monomer are effectively separated through specific liquid chromatography conditions, the system adaptability, specificity, linearity and range, detection limit, quantitation limit and accuracy verification of the method all meet acceptable standards of pharmacopoeia, and detection of multiple related substances can be completed within a short time; and a reliable means is provided for detecting and controlling the quality of the 5 '(E)-VPA phosphoramidite monomer.
Owner:QINGDAO TANGZHI PHARM TECH CO LTD

Synthesis of 5-nucleotide dithiophosphamide and application of 5-nucleotide dithiophosphamide in oligonucleotide

The invention discloses synthesis of 5-nucleotide phosphorodithioamide and application of the 5-nucleotide phosphorodithioamide in oligonucleotide. The oligonucleotide modified by the phosphorodithioamide comprises nucleotide structural units shown in a formula I or a formula II,..., the formula I,..., the formula II. According to the invention, through specific limitation of the structure of a nucleotide dithiophosphoramide monomer, the prepared oligonucleotide comprises a 5-nucleotide dithiophosphoramide structural unit. Compared with a traditional oligonucleotide molecule, the oligonucleotide molecule modified by nucleotide dithiophosphoramide shows better enzymatic degradation resistance and pharmaceutical stability. In addition, the binding performance between the modified oligonucleotide molecules and environmental ions can be improved through nucleotide dithiophosphamide modification, and a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.
Owner:SUZHOU SHENGNUOWEI BIOTECH CO LTD

Synthesis of 5-amino-3-nucleotide phosphamide and application of 5-amino-3-nucleotide phosphamide in oligonucleotide

The invention discloses synthesis of 5 '-amino-3-nucleotide phosphamide and application of the 5'-amino-3-nucleotide phosphamide in oligonucleotide. The phosphamide modified oligonucleotide comprises a nucleotide structural unit shown as a formula I or a formula II,..., the formula I; ... formula II; through specific limitation of a nucleotide phosphamide monomer structure, the prepared oligonucleotide contains a phosphamide structural unit; compared with a traditional oligonucleotide molecule, the oligonucleotide molecule with the phosphamide modified nucleotide structure has more excellent effects on pharmaceutical parameters such as enzymatic degradation resistance, stability and the like, and in addition, phosphamide modification can improve the binding performance between the modified oligonucleotide molecule and environmental ions; a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.
Owner:SUZHOU SHENGNUOWEI BIOTECH CO LTD

Non-aqueous electrolyte and lithium ion battery thereof

The invention provides a non-aqueous electrolyte and a lithium ion battery thereof. The non-aqueous electrolyte comprises an electrolyte salt, a non-aqueous organic solvent and an additive, wherein the additive comprises a bis (aziridinyl) phosphamide compound as shown in a structural formula I. Wherein R1 is selected from substituted or unsubstituted C1-C6 alkyl or substituted amino, the structural formula of the substituted amino is shown as a structural formula II or a structural formula III, R2, R3, R4, R5, R6, R7, R8, R9, R13, R14, R15 and R16 are respectively and independently selected from hydrogen and substituted or unsubstituted C1-C6 alkyl, and R11 and R12 are respectively and independently selected from substituted or unsubstituted C1-C6 alkyl. The mass ratio of the bis (aziridinyl) phosphamide compound is 0.01 to 1.00 percent. The non-aqueous electrolyte contains a specific flame retardant, can realize excellent flame retardant property only by low content, and has the flame retardant property and better high-temperature cycle and high-temperature storage performance when being used in the lithium ion battery. Structural formula I, structural formula II and structural formula III
Owner:HEFEI SMOOTHWAY ELECTRONIC MATERIALS CO LTD +2

P-chiral phosphine oxides containing alkynyl or triazole functional groups, and methods of making and using the same

The application discloses a five-membered ring containing alkynyl or triazole functional group P The chiral phosphine oxide compound is obtained through Domino Heck-Sonogashira cascade reaction by taking a prochiral tertiary phosphine oxide compound containing a double ethylene group and phenylacetylene as raw materials, transition metal palladium catalyst and chiral TADDOL phosphoramidite ligand under the protection of inert gas P The chiral phosphine oxide compound has a product yield of 96% and an enantioselectivity ee value of 99%, and a diastereoselectivity dr value of greater than 20:1. The application adopts an asymmetric desymmetrization strategy, uses a Heck reaction to start and a Sonogashira reaction to end a cascade reaction, simultaneously constructs P The chiral and quaternary carbon chiral center has mild reaction conditions, simple operation and good substrate universality, provides a compound skeleton with diversity, and is successfully applied to a palladium-catalyzed asymmetric allyl substitution reaction as a chiral ligand.
Owner:GUANGDONG UNIV OF TECH

Stable target editing guide RNA (Ribonucleic Acid) with introduction of phosphate modification

Provided is an oligonucleotide having excellent stability and capable of inducing ADAR editing activity in a cell. The oligonucleotide comprises a first oligonucleotide and a second oligonucleotide linked to the 5'side thereof, and induces site-specific editing against a target RNA. The first oligonucleotide is composed of a target-corresponding nucleotide residue, an oligonucleotide having 3 to 6 residues complementary to the target RNA on the 5'side thereof, and an oligonucleotide having 10 to 24 residues complementary to the target RNA on the 3 'side thereof. And at least one of a phosphorus-containing linking group connecting the nucleoside residues at the first position and the second position and a phosphorus-containing linking group connecting the nucleoside residues at the fourth position and the fifth position is an alkyl phosphonic acid residue, an alkyl phosphate residue or a substituted phosphamide residue. The second oligonucleotide has a nucleotide residue corresponding to the target RNA deleted at the 3'terminal, or has a nucleotide residue that does not form a complementary pair with the target RNA, the number of residues being 2 to 10, and the nucleotide residues other than the 3 'terminal being complementary to the target RNA.
Owner:FUKUOKA UNIV +1

A flame-retardant biodegradable polyester material and its preparation method

This invention relates to the field of polyester materials technology, and discloses a flame-retardant biodegradable polyester material and its preparation method. The polyester material of this invention is composed of 65-80 parts by weight of aromatic polyester, 20-35 parts by weight of aliphatic polyester, and 5-25 parts by weight of polylactic acid-based flame retardant. The aromatic polyester is selected from polyethylene terephthalate (PET), and the aliphatic polyester includes biodegradable components such as polylactic acid (PLA). The PLA-based flame retardant of this invention improves the compatibility between aliphatic polyesters such as PLA and aromatic polyesters such as PET, resulting in better mechanical properties. Simultaneously, the main chain contains a large number of phosphoramide groups, forming a nitrogen-phosphorus flame-retardant system, thereby improving the flame-retardant performance of the polyester material.
Owner:YANTAI JIAHE PLASTIC TECH CO LTD

Processes for producing nitriles and phosphorus-containing catalysts for use in such processes

A process for the hydrocyanation of an organic compound containing at least one olefinic group comprising reacting the organic compound with hydrogen cyanide in the presence of a catalyst complex comprising at least one transition metal and a phosphorus-containing ligand comprising a calixarene backbone and at least two aryl phosphite or aryl phosphoramidite groups chemically bonded to the backbone.
Owner:INV NYLON CHEMICALS AMERICAS LLC

An oligonucleotide cleavage reagent

This invention provides an oligonucleotide cleavage reagent (JS2 & S4 reagent) and its preparation method, as well as a method for cleaving oligonucleotides. The oligonucleotide cleavage reagent comprises NaOH, KOH, methanol, and a cleavage buffer. The oligonucleotide cleavage reagent JS2 & S4 and the cleavage method using it provided by this invention can efficiently cleave oligonucleotides, especially those synthesized using solid-phase phosphorous acid cleavage. This reduces chain breakage and side reactions caused by high-temperature cleavage, and also reduces equipment costs. While shortening the cleavage time, it can effectively reduce oligonucleotide quality problems caused by cleavage.
Owner:JIANGSU GENSCRIPT BIOTECH CO LTD

Ultra-dispersed ceramic white switch panel master batch as well as preparation method and application thereof

PendingCN121293630APolymer scienceTriazine
The invention discloses an ultra-dispersed ceramic white switch panel master batch as well as a preparation method and application thereof. Relates to the field of polymer materials. The ultra-dispersed ceramic white switch panel master batch comprises the following components: carrier resin, a modified flame retardant, a dispersing agent and a pigment, molecules of the modified flame retardant contain a triazine ring, benzyl, a phosphamide group and chloroethyl, and the benzyl serves as a connecting unit and is connected with the triazine ring, the phosphamide group and the chloroethyl. According to the ultra-dispersed ceramic white switch panel master batch disclosed by the invention, multi-performance optimization is realized through a synergistic effect of specific components.
Owner:ZHONGSHAN HUAYANG PLASTIC PIGMENT CO LTD

High-strength concrete and curing method thereof

The invention discloses high-strength concrete and a curing method thereof, and belongs to the technical field of concrete. The high-strength concrete comprises the following components: 300-400 kg / m < 3 > of cement, 100-130 kg / m < 3 > of silica fume, 50-80 kg / m < 3 > of fly ash, 700-850 kg / m < 3 > of sand, 850-950 kg / m < 3 > of gravel, 5-9 kg / m < 3 > of a modified polycarboxylate superplasticizer and 140-170 kg / m < 3 > of water. The modified polycarboxylate superplasticizer is formed by copolymerizing a methacrylate functional monomer containing a phosphamide anchoring group, an imidazolium zwitterionic monomer containing a styryl group, an acrylic monomer, a monoethyl fumarate monomer and an allyl polyoxyethylene ether monomer. Through molecular design, a strong anchoring phosphamide group and a mud-resistant zwitterionic structural monomer are introduced into the polycarboxylate superplasticizer, so that the strength of concrete is improved, and the service life of the concrete is prolonged.
Owner:TAISHAN JUNQIANG ELECTRIC POWER TELECOMM EQUIP CO LTD

Terminal thiophosphorylation modified threose nucleic acid and application thereof in oligonucleotide

The invention relates to the technical field of biological medicine, and particularly discloses synthesis and application of oligonucleotide with threose nucleic acid 3-oxygen at the tail end indirectly connected with thiophosphoric acid. The chemical modification strategy comprises the following steps: O < 3->-oxygen of threose nucleic acid is connected with thiophosphoric acid through a spacer group, and O < 2->-hydroxyl is combined with a nucleotide monomer of phosphoramidite; carrying out solid-phase synthesis on the threose nucleic acid O2 '-phosphoramidite monomer to construct an oligonucleotide molecule; the oxygen of the threose nucleic acid at the terminal of the oligonucleotide is linked to the thiophosphoric acid through a spacer group, and since the type of phosphonic acid does not belong to a substrate of phosphatase, the modified oligonucleotide can resist exonuclease degradation and improve its in vivo biological activity.
Owner:SUZHOU SHENGNUOWEI BIOTECH CO LTD

Method of synthesizing 4'-phosphate analog nucleotide phosphoramidite

PendingUS20260184736A1NucleotidePhosphoramides
Methods are disclosed for making a 4′-phosphate analog phosphoramidite known as MeMOP, which can be used in the synthesis of oligonucleotides such as therapeutic oligonucleotides.
Owner:ELI LILLY & CO

An imidazole-phosphoramidite bidentate ligand, a synthesis method thereof, a metal catalyst prepared by the same, and application thereof

The application provides an imidazole-phosphoramidite bidentate ligand, a synthesis method thereof, a metal catalyst prepared from the imidazole-phosphoramidite bidentate ligand and application of the metal catalyst, and relates to the technical field of catalyst preparation.The imidazole-phosphoramidite bidentate ligand developed by the application has stable chemical properties and is not easy to be oxidized, and solves the problems of poor stability of an imidazole-based bidentate ligand, harsh use and storage conditions in the prior art, and the synthesis method is simple, and the total yield can reach 59%; the imidazole-phosphoramidite bidentate ligand has strong coordination ability, the metal nickel catalyst prepared from the imidazole-phosphoramidite bidentate ligand has high catalytic activity, and in a carbon dioxide carboxylation reaction, the metal nickel catalyst exhibits excellent reaction activity, and is a ligand with very good industrial application prospect.
Owner:CHINA PETROLEUM & CHEMICAL CORP +1

Method for efficiently preparing various substituted chiral phosphamides

The invention provides a method for efficiently preparing various substituted chiral phosphoramides, which comprises the following steps: in the presence of an organic solvent, alkali, a chiral ligand and a catalyst, reacting a nucleoside compound or alcohol with racemic amino phosphoryl dichloride or alkoxy phosphoryl dichloride to generate chiral phosphoryl chloride; and reacting the chiral phosphoryl chloride with a nucleophilic reagent to obtain the chiral phosphamide. The synthesis method provided by the invention is simple to operate, high in yield and good in diastereoselectivity or enantioselectivity, and the obtained target compound has the characteristics of good functional group compatibility and wide substrate universality. The obtained product is diversified in structure and good in controllability, and has good application potential in the field of medicine synthesis.
Owner:SHANGHAI JIAOTONG UNIV

Nucleoside dimers, methods of making and use in DNA synthesis

The application provides a nucleoside dimer, a preparation method thereof and application in DNA synthesis. The nucleoside dimer of the application adopts a mixed skeleton of methyl phosphate and beta-cyanoethyl phosphoramidite, a new preparation method of the nucleoside dimer is obtained by optimizing a synthesis method and a purification process, and a foundation for high-quality DNA synthesis is laid. On this basis, the nucleoside dimer with the new skeleton is applied to DNA synthesis, an oligonucleotide fragment synthesis method suitable for the dimer is established, and an oligonucleotide fragment with a length of 100 nt is synthesized. Fidelity experiment shows that the error rate of the DNA fragment synthesized by using the dimer is only 3.75 errors / Kb, and high-fidelity DNA synthesis is realized. The preparation method of the nucleoside dimer with the new skeleton can realize large-scale and high-purity preparation, the nucleoside dimer can play an important role in improving the length and fidelity of oligonucleotide synthesis, and has practical value.
Owner:ACADEMY OF MILITARY MEDICAL SCIENCES

Phosphoramidite lipid molecule and use thereof in rnai molecule

The present invention belongs to the technical field of biochemistry, and specifically relates to a phosphoramidite lipid molecule and a use thereof in an RNAi molecule. In the present invention, a series of lipid molecules containing phosphoramidite are prepared and reacted with oligonucleotides to prepare an RNAi molecule. The RNAi molecule can effectively target extrahepatic tissues, while not interfering with the effect of inhibiting a target gene. The lipid molecule prepared in the present invention has good prospects in extrahepatic delivery vectors, and the RNAi molecule prepared in the present invention has important value for the research and development and clinical application of RNAi drugs.
Owner:LEADERNA THERAPEUTICS LTD

Application of spacer nucleic acid combined with threose or ethylene glycol nucleic acid in oligonucleotide

The invention relates to the technical field of biological medicines, and particularly discloses application of nucleotide with oxygen and phosphoramidite embedded spacer groups, threose nucleic acid TNA and ethylene glycol ribose GNA in oligonucleotides. The chemical modification strategy comprises the following steps: embedding nucleotide phosphoramidite of a spacer group between O3'and P (III), TNA phosphoramidite and GNA phosphoramidite to construct a target oligonucleotide molecule through solid-phase synthesis; the oligonucleotide comprises a nucleic acid unit with a spacer group embedded between O3'and phosphate P (V) and TNA or GNA, and the former can be directly coupled with the TNA or GNA and can also be linked with the TNA or GNA at an interval of one or more nucleotide units; the prepared and synthesized oligonucleotide contains a nucleotide unit of an O3 '-spacer group-P (V), can release O2'-hydroxyl, and is closer to the structure of natural nucleic acid. By finely adjusting the space structure of the modified oligonucleotide, the stability of the modified oligonucleotide drug molecule can be effectively improved, and the pharmacokinetic (PK) and pharmacodynamic (PD) performance can be optimized at the same time.
Owner:SUZHOU SHENGNUOWEI BIOTECH CO LTD

Anti-aging ethylene propylene diene monomer rubber compound

PendingCN121203325APolymer sciencePtru catalyst
The invention provides an anti-aging ethylene propylene diene monomer rubber compound which comprises a main material and an auxiliary material, the main material comprises the following components in parts by mass: 50-100 parts of maleic anhydride modified ethylene propylene diene monomer, 60-100 parts of a reinforcing filler, 40-60 parts of a plasticizer, 10-30 parts of N330 carbon black, 10-25 parts of mineral oil, 2-4 parts of an anti-aging agent, 1-5 parts of polyethylene glycol, 2-4 parts of a modifier, 2-5 parts of a compound containing a peroxy (O-O) structure, 3-10 parts of hyperbranched phosphamide modified graphene oxide and 5-10 parts of a calcium compound; 5-10 parts of hydrogenated silicone oil and 1.5-5 parts of an anti-aging agent; the auxiliary materials comprise the following components in parts by mass: 0.5-2 parts of stearic acid, 2-5 parts of zinc oxide, 10-15 parts of a solubilizer, 0.01-0.02 part of a catalyst and 0.2-0.5 part of a vulcanization accelerator; according to the present invention, with the synergistic effect of the peroxide (O-O) structure-containing compound, the hyperbranched phosphamide modified graphene oxide, the calcium compound and the hydrogenated silicone oil crosslinking, the strength and the toughness of the ethylene propylene diene monomer are enhanced, the damping performance of the ethylene propylene diene monomer is improved, the micro-damage is self-repaired in the thermal environment, the aging resistance of the rubber is increased, and the service life is prolonged.
Owner:ANHUI DINGLIAN POLYMER MATERIAL TECH CO LTD

Nucleotide modified by terminal thiophosphorylation and application of nucleotide in oligonucleotide

The invention relates to the technical field of biological medicine, and particularly discloses synthesis and application of oligonucleotide with a spacer group embedded in C4-oxygen and thiophosphoric acid at the tail end. The chemical modification strategy comprises the following steps: connecting C4-oxygen of nucleotide with thiophosphoric acid through a spacer group Y, and combining O3-hydroxyl with a nucleotide monomer of phosphoramidite; carrying out solid-phase synthesis on the nucleotide phosphoramidite to construct an oligonucleotide molecule; c4-oxygen at the tail end of the oligonucleotide is connected with thiophosphoric acid through a spacer group Y, the formed O4-Y-PSO22 < 2-> structure is phosphonic acid in a non-natural form and does not belong to a substrate of phosphatase, and the modified oligonucleotide can resist exonuclease degradation and improve the biological activity of the oligonucleotide.
Owner:SUZHOU SHENGNUOWEI BIOTECH CO LTD

Semi-aromatic nylon resin and synthesis method thereof

The invention discloses semi-aromatic nylon resin and a synthesis method thereof. The semi-aromatic nylon resin is synthesized from the following raw materials: decamethylene diamine, terephthalic acid, caprolactam, phosphamide-containing salt, toluene diisocyanate, organic copper chromite black, an acrylate copolymer and a high-temperature-resistant antioxidant. The semi-aromatic nylon resin has excellent mechanical properties, flame retardance and laser direct structuring performance, and can be widely applied to the communication field requiring flame retardance and laser direct structuring.
Owner:JIANGXI ZHONGSU NEW MATERIAL TECH CO LTD

LAT1-targeted phosphoramidated tyrosine PET molecular probe as well as preparation method and application thereof

The invention belongs to the field of nuclear medicine imaging agents, and relates to an LAT1 targeted phosphoramidated tyrosine PET molecular probe as well as a preparation method and application thereof. The probe has a structure as shown in a formula I. The LAT1-targeted phosphoramidated tyrosine PET molecular probe provided by the invention can be used for high-specificity uptake of bones, and has excellent in-vivo metabolism performance and bone uptake retention capacity. The targeted PET molecular probe provided by the invention has a clear tumor ratio, can be rapidly metabolized out of a body through a kidney, and has important application value for early and accurate diagnosis of bone tumors and bone metastatic tumors.
Owner:BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL

Process for the synthesis of phosphorodiamidate morpholino oligonucleotides

The application discloses a synthesis method of phosphorodiamidate morpholino oligonucleotide, belongs to the technical field of solid-phase synthesis of phosphorodiamidate morpholino oligonucleotide, and specifically relates to the following steps: adding 9-fluorenylmethyloxycarbonyl-piperazine-succinic acid into Wang resin to mix and react to synthesize 9-fluorenylmethyloxycarbonyl-piperazine-succinic acid-Wang resin, then adding phosphoramidite monomers to perform coupling reaction after deprotection treatment, performing cap treatment after the coupling is completed, then repeatedly performing deprotection treatment, coupling reaction and cap treatment until the coupling of all phosphoramidite monomers is completed, then removing the protecting group of the last phosphoramidite monomer, and then performing cleavage treatment and deprotection treatment of a base protecting group to obtain a phosphorodiamidate morpholino oligonucleotide (PMO) reaction solution. The application provides a synthesis method of phosphorodiamidate morpholino oligonucleotide with high coupling efficiency, low impurity level, high yield and high purity.
Owner:CHINESE PEPTIDE CO

Wide-temperature-range nonaqueous electrolyte, lithium ion battery, battery module, battery pack, power consuming device

This invention relates to the field of power battery technology, and in particular to a wide-temperature-range non-aqueous electrolyte, a lithium-ion battery, a battery module, a battery pack, and an electrical device. The non-aqueous electrolyte comprises lithium salts, solvents, and functional additives, wherein the functional additives include ammonium nitrate compounds represented by Formula I and phosphoramide compounds represented by Formula II. Both types of additives contain nitrogen (N), and they can mutually promote decomposition, jointly forming a dense, uniform, and thermally stable interface layer. This layer exhibits excellent ion conductivity at low temperatures and is not easily decomposed or broken at high temperatures.
Owner:ROLECHEM (JIANGSU) CO LTD +2