Soluble unsaturated diphosphonic acid quaternary ammonium double salt

Abstract

The invention provides a soluble unsaturated diphosphonic acid quaternary ammonium double salt and a preparation method thereof. The molecular structure of the soluble unsaturated diphosphonic acid quaternary ammonium double salt contains a plurality of units such as methyl diacryloyloxy or diacryloyloxy, tertiary amino, quaternary ammonium cations, diphosphonate or phosphonic acid choline and the like, and can be used for crosslinking copolymerization modification of methacrylate; the obtained copolymerized modified PMMA has antibacterial and bacteriostatic properties, medical efficacy of diphosphonate, biological activity of calcium-like phosphate, water absorption expansibility in a medium, reduced elasticity modulus of PMMA, improved tensile strength of PMMA, reduced curing heat effect of MMA, improved biocompatibility of PMMA and the like.

Description

Technical Field

[0001] The present invention relates to a soluble unsaturated phosphonate, in particular to a quaternary ammonium double salt of bisphosphonic acid containing bisacryloyloxy in its molecular structure and a preparation method thereof, which can be used for copolymer modification of polymethacrylate and belongs to the field of medical functional polymer materials. Technical Background

[0002] Polymethyl methacrylate (PMMA) is an artificially synthesized bio-inert polymer material, which has the characteristics of low density, good processing performance and good plasticity compared with metal materials and inorganic materials. As a bone cement for substituting bone materials, it is implanted into the body without triggering a host reaction, can remain biochemically stable when staying in the body for a long time, and has no cytotoxicity and no degradation. Compared with titanium metal, ceramics and other polymer-based bone substitution materials (such as polyethylene, polyaryletherketone and polyetheretherketone, etc.), PMMA-based bone cement can be cured at room temperature, and its good fluidity ensures that it can be made into a geometric shape completely matching the bone defect site during the operation, which is its greatest advantage in the bone tissue process. PMMA bone cement is composed of a powder component and a liquid component. The powder component is PMMA or modified PMMA micropowder with a mass percentage content of 80-89%, plus a developer, an initiator, an antibiotic, a modifier, etc.; the liquid component is methyl methacrylate (MMA) with a mass percentage content of 90-98%, and is externally equipped with a promoter, a stabilizer, a modifier, etc. Among them, whether using the powder component of modified PMMA or adding a modifier to the powder component and the liquid component respectively, the purpose is to eliminate the defects of PMMA-based bone cement.

[0003] The main defects revealed by PMMA-based bone cement used for more than half a century include: ① The elastic modulus of PMMA-based bone cement is extremely large. The elastic modulus of PMMA-based bone cement is 2552 MPa, which is much higher than the elastic modulus of trabecular bone (100-700 MPa). This difference will produce a stress shielding effect and a change in stress load transfer, resulting in an increased risk of adjacent vertebral fractures. ② The heat release during room temperature curing of PMMA-based bone cement is large. The heat released by the addition polymerization reaction of 1 g of MMA monomer in the liquid component of PMMA-based bone cement at room temperature is as high as 560 joules, causing a significant increase in the temperature of the bone cement. The maximum temperature of PMMA-based bone cement can reach 80-120 °C, which can cause necrosis of bone cells and bone tissue near the bone cement. ③ The shrinkage volume of the PMMA-based bone cement cured at room temperature is large. During the curing process of PMMA-based bone cement, the low-density MMA monomer (ρ = 0.94 g / cm 3 ) in the liquid component is polymerized into a PMMA polymer with a higher density (ρ = 1.19 g / cm 3) This leads to volume shrinkage after bone repair and filling, which is an important issue that must be paid attention to in clinical applications. ④ As an in-vivo implantable bio-inert polymer material, PMMA-based bone cement cannot be biodegradable in the body, nor can it induce the growth of bone cells and bone tissue, resulting in a low bone interface bonding force between it and the host. Therefore, the bone cement is prone to loosening after a period of time at the implantation site, ultimately causing bone repair failure. ⑤ Introducing antibiotics into PMMA-based bone cement is of great significance for preventing and treating acute and chronic osteoarticular infections after operations such as osteomyelitis, bone replacement, and fractures. ⑥ Incorporating some bisphosphonates with bone resorption inhibitory effects into PMMA-based bone cement has a positive effect on promoting the differentiation of osteoblasts and inhibiting the generation of osteoclasts.

[0004] According to the raw material types, preparation techniques, and usage methods of the above PMMA-based bone cement, relevant researchers, scholars, and medical workers at home and abroad have conducted targeted experimental studies and technical improvements on the defects of PMMA-based bone cement and achieved remarkable results. For example, filling and blending inorganic materials in the powder component of PMMA-based bone cement, including hydroxyapatite, bioactive glass, bentonite, TiO 2 nanofibers, halloysite nanotubes, carbon nanotubes, graphene oxide, etc., and using γ-methacryloxypropyltrimethoxysilane to surface-modify hydroxyapatite, bioactive glass, bentonite, etc., can all reduce the elastic modulus and heat release during curing of PMMA-based bone cement, enhance its tensile strength and flexural strength, and improve the bioactivity of PMMA-based bone cement. However, blending inorganic materials in the powder component will also cause some problems. For example, after the PMMA-grade bone cement is cured, the residual amount of MMA will gradually increase with the increase in the blending amount of inorganic materials, indicating that the inorganic material powder blocks the chain reaction of the free radical polymerization process. There are also cases where when preparing PMMA powder, some functional monomers are added to MMA, including acrylic acid, hydroxyethyl methacrylate, butyl methacrylate, 2-ethylhexyl acrylate, methacrylate quaternary ammonium salt, methacryloyl betaine, γ-methacryloxypropyltrimethoxysilane, ethylene glycol dimethacrylate, etc. for copolymerization modification, resulting in a reduction in the elastic modulus and cured body shrinkage of the copolymerization-modified PMMA-based bone cement, and significant improvement in its bioactivity and antibacterial properties. In short, so far, most of the modifications of PMMA-based bone cement through blending methods or copolymerization techniques are completed for single properties or functions, and it is relatively rare to have multiple modification effects taken into account.

[0005] Based on the properties, functions, and usage requirements of PMMA-based bone cement, aiming at the defects and deficiencies of existing modification technologies and methods, according to the chemical principle of molecular design, the present invention creates a double phosphonate quaternary salt containing bisacryloxy groups in its molecular structure as a functional bisacrylate crosslinking agent for copolymer crosslinking in MMA, expecting to play a positive role in improving and enhancing the antibacterial and bacteriostatic properties, medical efficacy of bisphosphonates, biocompatibility, water absorption and swelling properties in media, tensile strength of PMMA-based bone cement, as well as reducing the curing heat effect and elastic modulus, etc., realizing the optimization of many technical indicators of PMMA-based bone cement, and ensuring the safe, stable, and long-lasting applicability of PMMA-based bone cement. Summary of the Invention

[0006] The present invention provides a soluble unsaturated double phosphonate quaternary salt, which is characterized by having the structure shown in general formula (Ⅰ):

[0007]

[0008] Wherein R in general formula (Ⅰ) is selected from H or CH 3 , R 1 , R 2 and R 3 are respectively selected from C 1 ~C 18 hydrocarbon groups, X - refers to Cl - , Br - , NO 3 - , M n+ is selected from Na + , K + , NH 4 + , Ag + , Ca 2+ , Co 2+ , Cu 2+ , Zn 2+ , Sr 2+ , Mn 2+ , Mg 2+ , Al 3+ , Bi 3+ , Cr 3+ , Fe 3+ , Sn 4+ , Ti 4+ , Zr 4+, one of N-benzyl-N,N,N-trimethylammonium cation, N-benzyl-N,N,N-triethylammonium cation, N-benzyl-N,N,N-tributylammonium cation, N,N,N,N-tetrabutylammonium cation, N-dodecyl-N,N-dimethyl-N-benzylammonium cation, N-dodecyl-N,N-diethyl-N-benzylammonium cation, N-tetradecyl-N,N-dimethyl-N-benzylammonium cation or N-tetradecyl-N,N-diethyl-N-benzylammonium cation, where n is selected from 1, 2, 3 or 4.

[0009] The preparation method of the soluble unsaturated quaternary ammonium bisphosphonate complex salt of general formula (I) is as described below:

[0010] Step 1. Preparation of N,N-bis(2-hydroxy-3-(N’,N’-di-alkyl-N’-(ethyl-2-phosphonic acid) ammonium) propyl)-N-alkylamine of general formula (II)

[0011] At room temperature, put the solvent and N-glycidyl-N-(2-(bis-alkoxyphosphonyl) ethyl)-N,N-di-alkylammonium chloride into the reaction kettle to prepare a solution of N-glycidyl-N-(2-(bis-alkoxyphosphonyl) ethyl)-N,N-di-alkylammonium chloride with a mass percentage concentration of 5-50%. Control the temperature of the materials in the reaction kettle between -5 and 25 °C. Slowly add the primary amine. After the addition of the primary amine is completed, slowly raise the temperature to 50-60 °C and stir for 8-12 hours. Then use an aqueous acid solution with a mass percentage concentration of 15-50% to adjust the pH value of the materials in the reaction kettle ≤ 2. Raise the temperature of the materials in the reaction kettle to 80-120 °C and continue stirring for hydrolysis reaction for 6-24 hours. Lower the temperature of the materials in the reaction kettle to room temperature. Use an alkali to adjust the pH value of the materials in the reaction kettle to 7.0-9.0. Let it stand to precipitate the solid crude product. After filtration, recrystallization and drying to constant weight, obtain N,N-bis(2-hydroxy-3-(N’,N’-di-alkyl-N’-(ethyl-2-phosphonic acid) ammonium) propyl)-N-alkylamine with the structure shown in general formula (II):

[0012]

[0013] Wherein R in general formula (II) 1 , R 2 and R 3 are respectively selected from C 1 ~C 18 hydrocarbon groups.

[0014] The dosage of the primary amine is 0.48 - 0.50 times the molar amount of N-glycidyl-N-(2-(bis(alkoxyphosphoryl))ethyl)-N,N-dialkylammonium chloride, the dosage of the solvent is 0.5 - 5.0 times the mass of N-glycidyl-N-(2-(bis(alkoxyphosphoryl))ethyl)-N,N-dialkylammonium chloride, and the dosage of the aqueous acid solution is 1 - 10 times the mass of N-glycidyl-N-(2-(bis(alkoxyphosphoryl))ethyl)-N,N-dialkylammonium chloride.

[0015] The N-glycidyl-N-(2-(bis(alkoxyphosphoryl))ethyl)-N,N-dialkylammonium chloride has the structure shown in the general formula (Ⅲ):

[0016]

[0017] Among them, R in the general formula (Ⅲ) 2 and R 3 respectively select C 1 -C 18 alkyl groups, and R 4 selects one of methyl or ethyl; the alkyl group in the N-glycidyl-N-(2-(bis(alkoxyphosphoryl))ethyl)-N,N-dialkylammonium chloride refers to R 4 .

[0018] The solvent refers to one or more of water, methanol, ethanol, propanol, dichloromethane, chloroform, tetrahydrofuran, 1,4-dioxane, cyclohexane, decalin, acetonitrile, benzene, toluene, chlorobenzene or dimethyl sulfoxide.

[0019] The primary amine has the structure shown in the general formula (Ⅳ):

[0020] R 1 -NH 2

[0021] General formula (Ⅳ)

[0022] Among them, R in the general formula (Ⅳ) 1 selects C 1 -C 18 alkyl groups.

[0023] The aqueous acid solution refers to one of an aqueous hydrochloric acid solution or an aqueous sulfuric acid solution.

[0024] The base refers to one of sodium hydroxide, potassium hydroxide, sodium bicarbonate, sodium carbonate, potassium carbonate or ammonia water with a mass percentage concentration of 18 - 30%.

[0025] The preparation method of the general formula (III) N-glycidyl-N-(2-(bis(alkoxyphosphonyl))ethyl)-N,N-dialkylammonium chloride is as follows: An organic solvent and dimethyl vinylphosphonate or diethyl vinylphosphonate are added into a reaction kettle, and the temperature of the materials in the reaction kettle is controlled between -5°C and 25°C. Then, a secondary amine is slowly added into the reaction kettle. After the addition of the secondary amine is completed, the temperature is slowly raised to 50°C to 60°C and stirred for 8 to 12 hours. Then, epichlorohydrin is added, and the mixture is continuously stirred at a constant temperature for 12 to 48 hours. The temperature of the materials in the reaction kettle is lowered to 0°C to 20°C, and after filtration, washing, and drying to constant weight, the N-glycidyl-N-(2-(bis(alkoxyphosphonyl))ethyl)-N,N-dialkylammonium chloride with the structure shown in the general formula (III) is obtained:

[0026]

[0027] wherein R in the general formula (III) 2 and R 3 are respectively selected from C 1 to C 18 hydrocarbyl groups, and R 4 is selected from one of methyl or ethyl.

[0028] The dosage of the dimethyl vinylphosphonate or diethyl vinylphosphonate is 2.0 to 5.0 times the molar amount of the secondary amine, the dosage of the epichlorohydrin is 1.0 to 5.0 times the molar amount of the secondary amine, and the dosage of the organic solvent is 0 to 5 times the mass of the dimethyl vinylphosphonate or diethyl vinylphosphonate.

[0029] wherein the secondary amine has the structure shown in the general formula (V):

[0030]

[0031] wherein R in the general formula (V) 2 and R 3 are respectively selected from C 1 to C 18 hydrocarbyl groups.

[0032] The organic solvent refers to one or more of dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran, 1,4-dioxane, cyclohexane, decalin, acetonitrile, benzene, toluene, or chlorobenzene.

[0033] Step 2. Preparation of the soluble unsaturated bisphosphonic acid quaternary ammonium double salt of the general formula (I)

[0034] Add a non-protic solvent, a compound of the general formula (II) N,N-bis(2-hydroxy-3-(N’,N’-di-alkyl-N’-(ethyl-2-phosphonic acid) ammonium) propyl)-N-alkylamine, and an inhibitor into a reaction kettle. Control the temperature of the materials in the reaction kettle between 5 °C and 25 °C. After purging with nitrogen to remove oxygen, slowly add acryloyl chloride or methacryloyl chloride into the reaction kettle. After the feeding of acryloyl chloride or methacryloyl chloride is completed, raise the temperature of the materials in the reaction kettle to 50 °C - 60 °C and stir for 4 - 6 hours. Adjust the pH value of the materials in the reaction kettle to ≥ 7.5 using a 30% sodium hydroxide aqueous solution by mass concentration. Lower the temperature of the materials in the reaction kettle to room temperature, and then conduct negative pressure rotary evaporation for concentration, filtration, recrystallization, and vacuum drying to obtain a solid inner salt product; dissolve the solid inner salt product in deionized water in another reaction kettle to prepare an aqueous solution of the solid inner salt product with a mass concentration of 5% - 50%. Add an aqueous solution of inorganic salt under rapid stirring and conduct a metathesis reaction at room temperature for 0.5 - 5 hours. Then conduct negative pressure rotary evaporation for concentration, filtration, recrystallization, and drying to obtain a soluble unsaturated quaternary ammonium bisphosphonate complex salt with the structure shown in the general formula (I):

[0035]

[0036] wherein R in the general formula (I) is selected from H or CH 3 , R 1 , R 2 and R 3 are respectively selected from C 1 -C 18 alkyl groups, X - refers to Cl - , Br - , NO 3 - , M n+ is selected from Na + , K + , NH 4 + , Ag + , Ca 2+ , Co 2+ , Cu 2+ , Zn 2+ , Sr 2+ , Mn 2+ , Mg 2+ , Al 3+ , Bi 3+ , Cr 3+ , Fe 3+ , Sn 4+ , Ti 4+ , Zr 4+ ​, one of N-benzyl-N,N,N-trimethylammonium cation, N-benzyl-N,N,N-triethylammonium cation, N-benzyl-N,N,N-tributylammonium cation, N,N,N,N-tetrabutylammonium cation, N-dodecyl-N,N-dimethyl-N-benzylammonium cation, N-dodecyl-N,N-diethyl-N-benzylammonium cation, N-tetradecyl-N,N-dimethyl-N-benzylammonium cation or N-tetradecyl-N,N-diethyl-N-benzylammonium cation, where n is selected from one of 1, 2, 3 or 4.

[0037] The amount of the aprotic solvent is 0.5 to 15 times the mass of the N,N-bis(2-hydroxy-3-(N’,N’-di(hydrocarbyl)-N’-(ethyl-2-phosphonate)ammonio)propyl)-N-hydrocarbylamine, the amount of acryloyl chloride or methacryloyl chloride is 2.0 to 2.2 times the molar amount of the N,N-bis(2-hydroxy-3-(N’,N’-di(hydrocarbyl)-N’-(ethyl-2-phosphonate)ammonio)propyl)-N-hydrocarbylamine, the amount of the polymerization inhibitor is 0.013 to 0.03 times the mass of acryloyl chloride or methacryloyl chloride, the amount of deionized water is 0.5 to 5.0 times the mass of the N,N-bis(2-hydroxy-3-(N’,N’-di(hydrocarbyl)-N’-(ethyl-2-phosphonate)ammonio)propyl)-N-hydrocarbylamine, and the amount of the inorganic salt is 0.5 to 2.5 times the molar amount of the N,N-bis(2-hydroxy-3-(N’,N’-di(hydrocarbyl)-N’-(ethyl-2-phosphonate)ammonio)propyl)-N-hydrocarbylamine.

[0038] Wherein the polymerization inhibitor refers to one or more of hydroquinone, p-methoxyphenol, tert-butylhydroquinone, 2,6-dibutylhydroquinone, 2,6-di-tert-butyl-p-cresol or 2,4,6-tri-tert-butylphenol.

[0039] The aprotic solvent refers to one or more of tetrahydrofuran, 1,4-dioxane, cyclohexane, decalin, acetonitrile, chloroform, carbon tetrachloride, benzene, toluene, chlorobenzene, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide or N,N-dimethylacetamide.

[0040] The inorganic salt aqueous solution refers to dissolving the inorganic salt in deionized water, filtering to remove insoluble solid impurities, and preparing an inorganic salt aqueous solution with a mass percentage concentration of 5 to 50%.

[0041] The inorganic salts herein refer to one or more of sodium chloride, potassium chloride, ammonium chloride, sodium bromide, potassium bromide, ammonium bromide, sodium nitrate, potassium nitrate, ammonium nitrate, silver nitrate, calcium chloride, cobalt chloride hexahydrate, cobalt nitrate hexahydrate, copper chloride, basic copper chloride, ferrous chloride, magnesium hydroxide, zinc chloride, manganese nitrate, strontium dichloride, aluminum nitrate, aluminum chloride hexahydrate, basic bismuth nitrate, chromium chloride, ferric trichloride, tin tetrachloride pentahydrate, titanium nitrate, zirconium nitrate, basic zirconium chloride octahydrate, N-benzyl-N,N,N-trimethylammonium chloride, N-benzyl-N,N,N-triethylammonium chloride, N-benzyl-N,N,N-tributylammonium chloride, N,N,N,N-tetrabutylammonium chloride, N-dodecyl-N,N-dimethyl-N-benzylammonium chloride, N-dodecyl-N,N-diethyl-N-benzylammonium chloride, N-tetradecyl-N,N-dimethyl-N-benzylammonium chloride, N-tetradecyl-N,N-diethyl-N-benzylammonium chloride, N-benzyl-N,N,N-trimethylammonium bromide, N-benzyl-N,N,N-triethylammonium bromide, N-benzyl-N,N,N-tributylammonium bromide, N,N,N,N-tetrabutylammonium bromide, N-dodecyl-N,N-dimethyl-N-benzylammonium bromide, N-dodecyl-N,N-diethyl-N-benzylammonium bromide, N-tetradecyl-N,N-dimethyl-N-benzylammonium bromide, or N-tetradecyl-N,N-diethyl-N-benzylammonium bromide.

[0042] The beneficial effects of the soluble unsaturated bisphosphonic acid quaternary ammonium double salt of general formula (I) of the present invention are as follows:

[0043] ① The raw materials for preparing the soluble unsaturated bisphosphonic acid quaternary ammonium double salt of general formula (I) of the present invention are all commercially available products. The product yields in each step of the preparation process are high, the purification technology is simple and reliable, and the process is simple and easy to implement.

[0044] ② The molecular structure of the soluble unsaturated bisphosphonic acid quaternary ammonium double salt of general formula (I) of the present invention contains multiple units such as diallyloxy, tertiary amine group, quaternary ammonium cation, bisphosphonate, or phosphocholine. Theoretical prediction shows that when it is mixed into methyl methacrylate for copolymerization reaction, the resulting copolymer-modified PMMA will not only have the cross-linking modification effect, but also have antibacterial and bacteriostatic properties, the medical efficacy of bisphosphonate, the bioactivity of calcium phosphate-like, the water absorption and swelling in the medium, as well as the reduction of the elastic modulus of PMMA, the increase of the tensile strength of PMMA, the reduction of the curing heat effect of MMA, and the improvement of the biocompatibility of PMMA, etc., which can endow PMMA with various properties and optimized functions. Detailed implementation mode

[0045] For a further understanding of the present invention, the soluble unsaturated quaternary ammonium bisphosphonate salt of the present invention will be specifically described by way of examples, with the aim of better understanding the content of the present invention. Therefore, the omission of the soluble unsaturated quaternary ammonium bisphosphonate salt and its preparation method in the examples should not be regarded as a limitation on the protection scope of the present invention.

[0046] Example 1 Preparation of N-Glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibutylammonium Chloride

[0047] Charge 30 g of tetrahydrofuran, 60 g of diethyl vinylphosphonate and 45 g of dibutylamine into a reaction kettle. After reacting at a temperature of 20-25 °C for 2 hours, raise the temperature to 50-60 °C and stir for 12 hours. Then add 38 g of epichlorohydrin and continue to stir at a constant temperature for 36 hours. Lower the temperature of the materials in the reaction kettle to room temperature, let it stand to precipitate solids, filter, wash, and vacuum dry to constant weight to obtain 118.3 g of a white crystal product. Calculated based on dibutylamine, the yield of this white crystal product is 87.9%.

[0048]

[0049] The free chlorine content of this white crystal product was measured by titration analysis to be 9.15%. Other elemental analysis (%): C 51.78, H 9.73, N 3.61, P 8.01, which is basically in agreement with the calculated values of C 17 H 37 ClNO 4 P: C 52.91, H 9.66, Cl 9.19, N 3.63, P 8.03; its IR (KBr tablet, cm -1 ): 2973, 2878, 1537, 1435, 1362, 1256, 1108, 1073, 926 are respectively attributed to the characteristic vibration absorption peaks of methyl C-H, methylene C-H, C-N, P=O, C-O, P-O. 1 H-NMR (using TMS as the internal standard, DMSO-d 6 , δ): 0.87 (t, 6H), 1.13 (m, 6H), 1.34 (m, 4H), 1.73 (m, 4H), 2.22 (t, 2H), 2.38 (d, 2H), 3.16 (m, 1H), 3.24-3.48 (m, 8H), 4.09 (q, 4H). From the spectral analysis results of elemental analysis, IR and 1 H-NMR, it is confirmed that this white crystal product has the structural characteristics of N-Glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibutylammonium Chloride of formula (Ⅲ-1).

[0050] Preparation of Comparative Example 1: N-Glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibutylammonium Chloride

[0051] Charge 60 g of diethyl vinylphosphonate into the reaction kettle, control the temperature of the materials in the reaction kettle at 5 - 8 °C, slowly add 45 g of dibutylamine, after reacting for 12 hours, raise the temperature to 50 - 60 °C and stir and react for 12 hours, then charge 120 g of epichlorohydrin, continue to keep warm and stir and react for 36 hours, lower the temperature of the materials in the reaction kettle to room temperature, let it stand to precipitate solid products, filter, wash with chloroform, and vacuum dry to constant weight to obtain 120.7 g of white crystal products. The product yield calculated based on dibutylamine is 89.6%. Using the same analysis and characterization method as in Example 1, it is confirmed that the white crystal products have the structural characteristics of N-glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibutylammonium chloride of formula (Ⅲ-1).

[0052] Preparation of Example 2: N-Glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibenzylammonium Chloride

[0053] According to the method and steps of Example 1, change dibutylamine in Example 1 to dibenzylamine, then white solid products are obtained. The product yield calculated based on dibenzylamine is 65.3%. Using the same analysis and characterization method as in Example 1, it is confirmed that the white solid products have the structural characteristics of N-glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibenzylammonium chloride of formula (Ⅲ-2):

[0054]

[0055] Preparation of Example 3: N-Glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N-dodecyl-N-benzylammonium Chloride

[0056] According to the method and steps of Example 1, change dibutylamine in Example 1 to N-dodecyl-N-benzylamine, then white solid products are obtained. The product yield calculated based on N-dodecyl-N-benzylamine is 67.6%. Using the same analysis and characterization method as in Example 1, it is confirmed that the white solid products have the structural characteristics of N-glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N-dodecyl-N-benzylammonium chloride of formula (Ⅲ-3):

[0057]

[0058] Preparation of Example 4: N,N-Bis(2-hydroxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonate)ammonio)propyl)-N-benzylamine

[0059] Into a reaction kettle, 100 g of deionized water and 25 g of N-glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibutylammonium chloride of formula (III-1) were added. After stirring and dissolving, the temperature of the materials in the reaction kettle was controlled between 0 and 5 °C. Among them, a mixture of 3.5 g of benzylamine and 5 g of ethanol was slowly added. After the addition of the benzylamine ethanol solution was completed, the temperature was slowly raised to 50 - 60 °C and stirred for 12 hours. Then, 12 g of concentrated hydrochloric acid was added and the temperature of the materials in the reaction kettle was raised to 80 - 90 °C, and stirring was continued for the hydrolysis reaction for 12 hours. The temperature of the materials in the reaction kettle was lowered to room temperature, and the solid product was filtered out. The solid product was just dissolved with an appropriate amount of deionized water, and the pH value was adjusted to 7.5 with a 30% by mass aqueous sodium hydroxide solution and then concentrated. After filtration, recrystallization with ethanol, and vacuum drying to constant weight, a white solid product was obtained. The elemental analysis (%) of the white solid product: C 52.38, H 9.63, N 3.61, P 8.01, which is basically in agreement with the calculated values of C 33 H 65 N 3 O 8 P 2 52.91, H 9.66, Cl 9.19, N 3.63, P 8.03; its IR (KBr tablet, cm -1 ): 3246, 2963, 2873, 1537, 1435, 1362, 1256, 1108, 1037, 974, 926 are respectively attributed to the characteristic vibration absorption peaks of methyl O-H, C-H, methylene C-H, C-N, P=O, C-O, P-O. 1 H-NMR (using TMS as the internal standard, DMSO-d 6 , δ): 0.96 (t, 12H), 1.31 (m, 8H), 1.73 (m, 8H), 1.84 (m, 4H), 2.08 - 2.12 (s, 4H), 2.68 (d, 4H), 3.22 - 3.34 (m, 16H), 3.64 (s, 2H), 4.08 (m, 2H), 7.12 - 7.36 (m, 5H). From the spectral analysis results of elemental analysis, IR, and 1 H-NMR, it was confirmed that the white crystal product has the structural characteristics of N,N-bis(2-hydroxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonic acid)ammonio)propyl)-N-benzylamine of formula (II-1):

[0060]

[0061] Example 5 Preparation of N,N-bis(2-hydroxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonic acid)ammonio)propyl)-N-benzylamine

[0062] According to the method and steps of Example 4, change N-glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibutylammonium chloride of formula (Ⅲ-1) in Example 1 to N-glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibenzylammonium chloride of formula (Ⅲ-2), and change benzylamine to dodecylamine, then a white solid product is obtained. Using the same analysis and characterization method as in Example 4, it is confirmed that this white solid product has the structural characteristics of N,N-bis(2-hydroxy-3-(N',N'-dibenzyl-N'-(ethyl-2-phosphonic acid)ammonio)propyl)-N-dodecylamine of formula (Ⅱ-2):

[0063]

[0064] Example 6 Preparation of N,N-bis(2-hydroxy-3-(N'-dodecyl-N'-benzyl-N'-(ethyl-2-phosphonic acid)ammonio)propyl)-N-benzylamine

[0065] According to the method and steps of Example 4, change N-glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N,N-dibutylammonium chloride of formula (Ⅲ-1) in Example 1 to N-glycidyl-N-(2-(diethoxyphosphoryl)ethyl)-N-dodecyl-N-benzylammonium chloride of formula (Ⅲ-3), then a white solid product is obtained. Using the same analysis and characterization method as in Example 4, it is confirmed that this white solid product has the structural characteristics of N,N-bis(2-hydroxy-3-(N'-dodecyl-N'-benzyl-N'-(ethyl-2-phosphonic acid)ammonio)propyl)-N-benzylamine of formula (Ⅱ-3):

[0066]

[0067] Example 7 Preparation of Soluble Unsaturated Bisphosphonic Acid Quaternary Ammonium Silver Double Salt of Formula (Ⅰ-1)

[0068] Add 42 g of 1,4-dioxane, 14.3 g of N,N-bis(2-hydroxy-3-(N',N'-dibutyl-N'-(ethyl-2-phosphonic acid)ammonio)propyl)-N-benzylamine of formula (Ⅱ-1) and 0.38 g of 2,6-di-tert-butyl-p-cresol into the reaction kettle. Control the temperature of the materials in the reaction kettle between 5 and 25 °C. After filling with nitrogen to remove oxygen and stirring evenly, slowly add 8.3 g of methacryloyl chloride to the reaction kettle. After the methacryloyl chloride feeding is completed, raise the temperature of the materials in the reaction kettle to 50 - 60 °C and stir for 6 hours. After concentration under negative pressure, filtration, washing, and vacuum drying, a white solid primary product is obtained.

[0069] The free chlorine content of the primary white solid product was measured by titration analysis to be 7.64%. The elemental analysis (%) of the primary white solid product: C 54.08, H 8.37, N 3.61, P 8.01, which is basically consistent with the calculated values of C 41 H 75 Cl 2 N 3 O 10 P 2 C 55.54, H 8.37, Cl 7.85, N 4.65, P 6.86; its IR (KBr tablet, cm -1 ): 3246, 3022, 2932, 2876, 1725, 1633, 1538, 1438, 1259, 1106, 1036, 968 are respectively attributed to characteristic vibration absorption peaks such as O-H, C═C-H, methyl C-H, methylene C-H, C═O, C═C, C-N, P═O, C-O, P-O, etc. 1 1H-NMR (TMS as internal standard, DMSO-d 6 , δ): 0.89 (t, 12H), 1.12 (m, 12H), 1.34 (m, 8H), 1.74 (m, 8H), 1.93 (s, 4H), 2.23 (q, 2H), 2.38 (d, 4H), 3.16 (m, 2H), 3.24 - 3.48 (m, 12H), 4.50 (q, 2H), 5.42 - 5.84 (s, 4H), 7.14 - 7.68 (m, 5H). From the spectral analysis results of elemental analysis, IR and 1 1H-NMR, it was confirmed that the primary white solid product has the structural characteristics of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonic acid) ammonium chloride) propyl)-N-benzylamine of formula (Ⅱ-1-1):

[0070]

[0071] 15 g of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonic acid) ammonium chloride) propyl)-N-benzylamine of formula (Ⅰ-1-1) was dissolved in 50 g of deionized water to prepare an aqueous solution of the primary solid product. At room temperature, the pH value of the aqueous solution of the primary solid product was adjusted to ≥7.5 with a 30% sodium hydroxide aqueous solution by mass concentration. Then, it was concentrated by negative pressure rotary evaporation, filtered, recrystallized with ethanol, and dried in vacuum to obtain a white crystalline product. By the same analysis and characterization methods as in Example 7, it was confirmed that the white crystalline product has the structure of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonic acid) ammonium) propyl)-N-benzylamine shown in formula (Ⅰ-1-2):

[0072]

[0073] At room temperature, 15 g of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonate)ammonium)propyl)-N-benzylamine of formula (I-1-2) was dissolved in 50 g of deionized water to prepare an aqueous solution, and then rapidly stirred. While avoiding light, 50 g of an aqueous silver nitrate solution with pH = 5.5 and molar concentration = 0.053 M was slowly added. After negative pressure concentration, filtration, recrystallization, and vacuum drying, a grayish-white powdery product was obtained. By the same analysis and characterization methods as in Example 7, it was confirmed that this grayish-white powdery product was a soluble unsaturated quaternary ammonium silver bisphosphonate complex salt having the structure shown in formula (I-1):

[0074]

[0075] Example 8 Preparation of Soluble Unsaturated Quaternary Ammonium Zinc Bisphosphonate Complex Salt of Formula (I-2)

[0076] According to the method and steps of Example 7, 15 g of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonate)ammonium)propyl)-N-benzylamine of formula (I-1-2) was dissolved in 50 g of deionized water to prepare an aqueous solution. At room temperature, while rapidly stirring, 50 g of an aqueous zinc chloride solution with pH = 5.5 and molar concentration = 0.25 M was added. After negative pressure concentration, filtration, recrystallization, and vacuum drying, a white powdery product was obtained. By the same analysis methods and characterization as in Example 7, it was confirmed that this white powdery product was a soluble unsaturated quaternary ammonium zinc bisphosphonate complex salt having the structure shown in formula (I-2):

[0077]

[0078] Example 9 Preparation of Soluble Unsaturated Quaternary Ammonium Chromium Bisphosphonate Complex Salt of Formula (I-3)

[0079] According to the method and steps of Example 7, 15 g of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonate)ammonium chloride)propyl)-N-benzylamine of formula (I-1-2) was dissolved in 50 g of deionized water to prepare an aqueous solution. While rapidly stirring, 50 g of an aqueous chromium chloride solution with pH = 5.5 and molar concentration = 0.25 M was added. After negative pressure concentration, filtration, recrystallization, and vacuum drying, a blue-violet crystal product was obtained. By the same analysis methods and characterization as in Example 7, it was confirmed that this blue-violet crystal product was a soluble unsaturated quaternary ammonium chromium bisphosphonate complex salt having the structure shown in formula (I-3):

[0080]

[0081] Preparation of Soluble Unsaturated Quaternary Ammonium Silver Bisphosphonate Complex Salt of Formula (Ⅰ-4) in Example 10

[0082] According to the method and steps of Example 7, change N,N-bis(2-hydroxy-3-(N’,N’-dibutyl-N’-(ethyl-2-phosphonate) ammonium) propyl)-N-benzylamine of formula (Ⅱ-1) in Example 7 to N,N-bis(2-hydroxy-3-(N’,N’-dibenzyl-N’-(ethyl-2-phosphonate) ammonium) propyl)-N-dodecylamine of formula (Ⅱ-2). Similarly, prepare N,N-bis(2-methacryloyloxy-3-(N’,N’-dibenzyl-N’-(ethyl-2-phosphonate) ammonium chloride) propyl)-N-dodecylamine of formula (Ⅱ-2-1) and N,N-bis(2-methacryloyloxy-3-(N’,N’-dibenzyl-N’-(ethyl-2-phosphonate) ammonium) propyl)-N-dodecylamine of formula (Ⅱ-2-2) respectively.

[0083]

[0084] Take 21 g of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibenzyl-N’-(ethyl-2-phosphonate) ammonium) propyl)-N-dodecylamine of formula (Ⅱ-2-2) and dissolve it in 63 g of deionized water to prepare an aqueous solution. Stir rapidly at room temperature, and then add 50 g of silver nitrate aqueous solution with pH = 5.5 and molar concentration = 0.103 M thereto in the dark. After negative pressure concentration, filtration, recrystallization, and vacuum drying, a grayish-white powdery product is obtained. Through the same analysis method and characterization as in Example 7, it is confirmed that the grayish-white powdery product is a soluble unsaturated quaternary ammonium silver bisphosphonate complex salt with the structure shown in formula (Ⅰ-4):

[0085]

[0086] Preparation of Soluble Unsaturated Quaternary Ammonium Calcium Bisphosphonate Complex Salt of Formula (Ⅰ-5) in Example 11

[0087] According to the method and steps of Example 10, take 21 g of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibenzyl-N’-(ethyl-2-phosphonate) ammonium) propyl)-N-dodecylamine of formula (Ⅱ-2-2) and dissolve it in 50 g of deionized water to prepare an aqueous solution. Stir rapidly at room temperature, and then add 50 g of calcium chloride aqueous solution with molar concentration = 0.15 M thereto in the dark. After negative pressure concentration, filtration, recrystallization, and vacuum drying, a white powdery product is obtained. Through the same analysis method and characterization as in Example 7, it is confirmed that the white powdery product is a soluble unsaturated quaternary ammonium calcium bisphosphonate complex salt with the structure shown in formula (Ⅰ-5):

[0088]

[0089] Preparation of Soluble Unsaturated Quaternary Ammonium Calcium Salt of Bisphosphonic Acid of Formula (Ⅰ-6) in Example 12

[0090] According to the method and steps of Example 10, 18 g of N,N-bis(2-methacryloyloxy-3-(N’,N’-dibenzyl-N’-(ethyl-2-phosphonic acid) ammonium) propyl)-N-dodecylamine of formula (Ⅱ-2-2) was dissolved in 50 g of deionized water to prepare an aqueous solution, which was rapidly stirred at room temperature. Then, 50 g of an aqueous solution of tetrabutylammonium bromide with a molar concentration of 0.15 M was added thereto in the dark. After concentration under negative pressure, filtration, recrystallization, and vacuum drying, a white crystalline product was obtained. Through the same analysis method and characterization as in Example 7, it was confirmed that the white crystalline product was a soluble unsaturated quaternary ammonium calcium salt of bisphosphonic acid having the structure shown in formula (Ⅰ-6):

[0091]

[0092] Example 13 Solubility of Soluble Unsaturated Quaternary Ammonium Salts of Bisphosphonic Acid in Examples 7 to 12

[0093] In a certain amount of deionized water, ethanol, ethyl acetate, acetonitrile, and toluene, the soluble unsaturated quaternary ammonium salts of bisphosphonic acid in Examples 7 to 12 were respectively added, and the temperature was controlled and oscillated for dissolution for 24 hours. The dissolution of the soluble unsaturated quaternary ammonium salts of bisphosphonic acid was observed, and the results are shown in Table 1.

[0094] Table 1 Solubility of Soluble Unsaturated Quaternary Ammonium Salts of Bisphosphonic Acid in Examples 7 to 12 *

[0095]

[0096] * Note: The term "soluble" means that the room temperature dissolution amount of the soluble unsaturated quaternary ammonium salt of bisphosphonic acid in 100 g of the solvent is greater than 10 g; the term "hot soluble" means that at a temperature of 60 °C, the dissolution amount of the soluble unsaturated quaternary ammonium salt of bisphosphonic acid in 100 g of the solvent is greater than 10 g; the term "thermally soluble" means that at a temperature of 60 °C, the dissolution amount of the soluble unsaturated quaternary ammonium salt of bisphosphonic acid in 100 g of the solvent is less than 10 g; the term "thermally slightly soluble" means that at a temperature of 60 °C, the dissolution amount of the soluble unsaturated quaternary ammonium salt of bisphosphonic acid in 100 g of the solvent is less than 2 g.

Claims

1. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt, characterized in that The soluble unsaturated bisphosphonic acid quaternary ammonium double salt has a structure shown in general formula (I): Wherein R in the general formula (I) is selected from H or CH3, R1, R2 and R3 are selected from C1 to C 18 Hydrocarbon, X - Refers to Cl - Br - 、NO3 - , M n+ Select Na + , K + NH4 + 、Ag + , Ca 2+ 、Co 2+ , Cu 2+ , Fe 2+ Mg 2+ , Mn 2+ 、Zn 2+ , Sr 2+ 、Al 3+ 、Bi 3+ Cr 3+ , Fe 3+ Sn 4+ 、Ti 4+ 、Zr 4+ , N-benzyl-N,N,N-trimethylammonium cation, N-benzyl-N,N,N-triethylammonium cation, N-benzyl-N,N,N-tributylammonium cation, N,N,N,N-tetrabutylammonium cation, N-dodecyl-N,N-dimethyl-N-benzylammonium cation, N-dodecyl-N,N-diethyl-N-benzylammonium cation, N-tetradecyl-N,N-dimethyl-N-benzylammonium cation or N-tetradecyl-N,N-diethyl-N-benzylammonium cation, wherein n is selected from one of 1, 2, 3 or 4; The preparation method of the soluble unsaturated bisphosphonic acid quaternary ammonium double salt is achieved by taking the following steps: Step 1: Preparation of N,N-di(2-hydroxy-3-(N',N'-dialkyl-N'-(ethyl-2-phosphonic acid)ammonium)propyl)-N-alkylamine At room temperature, a solvent and N-glycidyl-N-(2-(bisalkoxyphosphonyl)ethyl)-N,N-dialkylammonium chloride are added to a reaction kettle to prepare a 5-50% N-glycidyl-N-(2-(bisalkoxyphosphonyl)ethyl)-N,N-dialkylammonium chloride solution, and then the temperature of the material in the reaction kettle is controlled between -5 and 25°C, and the primary amine is slowly added. After the primary amine is added, the temperature of the material in the high-temperature reaction kettle is slowly increased to 50-60°C, and the reaction is stirred for 8-12 hours. The mass percentage concentration is used. 15-50% acid aqueous solution is used to adjust the pH value of the material in the reactor to ≤ 2, the temperature of the material in the reactor is increased to 80-120°C, and the stirring is continued to carry out the hydrolysis reaction for 6-24 hours, and the temperature of the material in the reactor is reduced to room temperature. The pH value of the material in the reactor is adjusted to 7.0-9.0 with alkali, and the solid crude product is precipitated by standing, filtered, recrystallized, and dried to constant weight to obtain N,N-di(2-hydroxy-3-(N',N'-dialkyl-N'-(ethyl-2-phosphonic acid)ammonium)propyl)-N-alkylamine of the structure shown in general formula (II): Wherein R1, R2 and R3 in the general formula (II) are selected from C1 to C 18 Hydrocarbon; The amount of the primary amine is 0.48 to 0.50 times the molar amount of N-glycidyl-N-(2-(dialkoxyphosphonyl)ethyl)-N,N-dialkylammonium chloride, the amount of the solvent is 0.5 to 5.0 times the mass of N-glycidyl-N-(2-(dialkoxyphosphonyl)ethyl)-N,N-dialkylammonium chloride, and the amount of the acid aqueous solution is 1 to 10 times the mass of N-glycidyl-N-(2-(dialkoxyphosphonyl)ethyl)-N,N-dialkylammonium chloride; The N-glycidyl-N-(2-(bisalkoxyphosphonyl)ethyl)-N,N-dialkylammonium chloride has a structure shown in the general formula (III): Wherein R2 and R3 in the general formula (III) are selected from C1 to C 18 Hydrocarbyl, R4 is selected from methyl or ethyl; The primary amine has a structure shown in general formula (IV): R1 - NH2 General formula (Ⅳ) Wherein R1 of the general formula (Ⅳ) is selected from C1~C 18 Hydrocarbon; Step 2: Preparation of Soluble Unsaturated Bisphosphonic Acid Quaternary Ammonium Double Salt of General Formula (I) A nonprotonic solvent, general formula (II) N,N-di(2-hydroxy-3-(N',N'-dialkyl-N'-(ethyl-2-phosphonic acid) ammonium)propyl)-N-alkylamine and a polymerization inhibitor are added to a reactor, the temperature of the material in the reactor is controlled between 5 and 25°C, acryloyl chloride or methacryloyl chloride is slowly added to the reactor after nitrogen filling and deoxygenation, and after acryloyl chloride or methacryloyl chloride is added, the temperature of the material in the reactor is raised to 50-60°C, and the reaction is stirred for 4-6 hours, and a caustic soda aqueous solution with a mass percentage concentration of 30% is used to adjust the reaction temperature of the reactor. The pH value of the material is ≥7.5, the temperature of the material in the reactor is reduced to room temperature, and then concentrated by negative pressure rotary evaporation, filtered, recrystallized, and dried in vacuo to obtain a solid inner salt product; the solid inner salt product is dissolved in deionized water in another reactor to prepare a solid inner salt product aqueous solution with a mass percentage concentration of 5 to 50%, an inorganic salt aqueous solution is added thereto under rapid stirring, and a double decomposition reaction is carried out at room temperature for 0.5 to 5 hours, and then concentrated by negative pressure rotary evaporation, filtered, recrystallized, and dried to obtain a soluble unsaturated bisphosphonic acid quaternary ammonium double salt with a structure shown in general formula (I); The amount of the aprotic solvent is 0.5 to 15 times the mass of the N,N-di(2-hydroxy-3-(N',N'-dialkyl-N'-(ethyl-2-phosphonic acid)ammonium)propyl)-N-alkylamine, the amount of acryloyl chloride or methacryloyl chloride is 2.0 to 2.2 times the molar amount of the N,N-di(2-hydroxy-3-(N',N'-dialkyl-N'-(ethyl-2-phosphonic acid)ammonium)propyl)-N-alkylamine, and the amount of the inhibitor is acryloyl chloride. or 0.013 to 0.03 times the mass of methacryloyl chloride, the amount of deionized water is 0.5 to 5.0 times the mass of the N,N-di(2-hydroxy-3-(N',N'-dialkyl-N'-(ethyl-2-phosphonic acid)ammonium)propyl)-N-alkylamine, and the amount of the inorganic salt is 0.5 to 2.5 times the molar amount of the N,N-di(2-hydroxy-3-(N',N'-dialkyl-N'-(ethyl-2-phosphonic acid)ammonium)propyl)-N-alkylamine.

2. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt according to claim 1, characterized in that The solvent refers to one or more of water, methanol, ethanol, propanol, dichloromethane, chloroform, tetrahydrofuran, 1,4-dioxane, cyclohexane, decahydronaphthalene, acetonitrile, benzene, toluene, chlorobenzene or dimethyl sulfoxide.

3. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt according to claim 1, characterized in that The acid aqueous solution refers to one of a hydrogen chloride aqueous solution or a sulfuric acid aqueous solution.

4. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt according to claim 1, characterized in that The alkali refers to sodium hydroxide, potassium hydroxide, sodium bicarbonate, sodium carbonate, potassium carbonate or one of ammonia water with a mass percentage concentration of 18-30%.

5. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt and a preparation method thereof according to claim 1, characterized in that The polymerization inhibitor refers to one or more of hydroquinone, p-methoxyphenol, tert-butylhydroquinone, 2,6-dibutylhydroquinone, 2,6-di-tert-butyl-p-cresol or 2,4,6-tri-tert-butylphenol.

6. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt according to claim 1, characterized in that The aprotic solvent refers to one or more of tetrahydrofuran, 1,4-dioxane, cyclohexane, decahydronaphthalene, acetonitrile, chloroform, carbon tetrachloride, benzene, toluene, chlorobenzene, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide or N,N-dimethylacetamide.

7. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt according to claim 1, characterized in that The inorganic salt aqueous solution refers to dissolving the inorganic salt in deionized water, filtering to remove insoluble solid impurities, and preparing an inorganic salt aqueous solution with a mass percentage concentration of 5 to 50%; The inorganic salts include sodium chloride, potassium chloride, ammonium chloride, sodium bromide, potassium bromide, ammonium bromide, sodium nitrate, potassium nitrate, ammonium nitrate, silver nitrate, calcium chloride, cobalt chloride hexahydrate, cobalt nitrate hexahydrate, cupric chloride, basic cupric chloride, ferrous chloride, magnesium hydroxide, zinc chloride, manganese nitrate, strontium dichloride, aluminum nitrate, hydrated aluminum chloride, basic bismuth nitrate, chromium chloride, ferric chloride, tin tetrachloride pentahydrate, titanium nitrate, zirconium nitrate, basic zirconium chloride octahydrate, N-benzyl-N,N,N-trimethylammonium chloride, N-benzyl-N,N,N-triethylammonium chloride, N-benzyl-N,N,N-tributylammonium chloride, N,N,N,N-tetrabutylammonium chloride, N-dodecyl-N,N-dimethyl-N-benzyl chloride ammonium, N-dodecyl-N,N-diethyl-N-benzyl ammonium chloride, N-tetradecyl-N,N-dimethyl-N-benzyl ammonium chloride, N-tetradecyl-N,N-diethyl-N-benzyl ammonium chloride, N-benzyl-N,N,N-trimethylammonium bromide, N-benzyl-N,N,N-triethylammonium bromide, N-benzyl-N,N,N-tributylammonium bromide, N,N,N,N-tetrabutylammonium bromide, N-dodecyl-N,N-dimethyl-N-benzyl ammonium bromide, N-dodecyl-N,N-diethyl-N-benzyl ammonium bromide, N-tetradecyl-N,N-dimethyl-N-benzyl ammonium bromide, or one or more of N-tetradecyl-N,N-diethyl-N-benzyl ammonium bromide.

8. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt according to claim 1, characterized in that The preparation method of the general formula (III) N-glycidyl-N-(2-(bisalkoxyphosphonyl)ethyl)-N,N-dialkylammonium chloride is as follows: an organic solvent and dimethyl vinylphosphonate or diethyl vinylphosphonate are added into a reaction kettle, the temperature of the materials in the reaction kettle is controlled between -5 and 25° C., a secondary amine is slowly added into the reaction kettle, after the secondary amine is added, the temperature is slowly raised to 50 to 60° C. and stirred for reaction for 8 to 12 hours, epichlorohydrin is added, the temperature is kept warm and stirred for reaction for 12 to 48 hours, the temperature of the materials in the reaction kettle is lowered to 0 to 20° C., the reaction is filtered, washed, and dried to constant weight to obtain N-glycidyl-N-(2-(bisalkoxyphosphonyl)ethyl)-N,N-dialkylammonium chloride with a structure shown in the general formula (III): Wherein R2 and R3 in the general formula (III) are selected from C1 to C 18 Hydrocarbyl, R4 is selected from methyl or ethyl; The amount of the dimethyl vinylphosphonate or diethyl vinylphosphonate is 2.0 to 5.0 times the molar amount of the secondary amine, the amount of epichlorohydrin is 1.0 to 5.0 times the molar amount of the secondary amine, and the amount of the organic solvent is 0 to 5 times the mass of the dimethyl vinylphosphonate or diethyl vinylphosphonate; The secondary amine has a structure shown in the general formula (V): Wherein R2 and R3 in the general formula (V) are selected from C1 to C 18 Hydrocarbon.

9. A soluble unsaturated bisphosphonic acid quaternary ammonium double salt according to claim 8, characterized in that The organic solvent refers to one or more of dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran, 1,4-dioxane, cyclohexane, decahydronaphthalene, acetonitrile, benzene, toluene or chlorobenzene.

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