CN106928398A - A kind of medical acrylic acid class thickener and preparation method thereof - Google Patents
A kind of medical acrylic acid class thickener and preparation method thereof Download PDFInfo
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- CN106928398A CN106928398A CN201710256545.2A CN201710256545A CN106928398A CN 106928398 A CN106928398 A CN 106928398A CN 201710256545 A CN201710256545 A CN 201710256545A CN 106928398 A CN106928398 A CN 106928398A
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
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Abstract
The invention discloses a kind of preparation method of medical acrylic acid class thickener, comprise the following steps：Step 1：Under nitrogen protection, to the first monomer, solvent, dispersant is added in reactor, stir and be warming up to 55~80 DEG C；Step 2：To the initiator for adding 15~20wt% in the reactor of step 1 in the way of being added dropwise respectively, time for adding is 0.5~1 hour；Then second comonomer and remaining initiator, isothermal reaction 2~6 hours are added in the way of being added dropwise；The first described monomer and the weight ratio of second comonomer are 1:3~4；Step 3：Reaction terminates rear suction filtration, and again disperses sediment with solvent after being washed for several times with solvent；Step 4：The mixture of step 3 is dried in the form of being spray-dried, dried dust is collected and is obtained final product.It is an object of the invention to provide a kind of preparation method of the few medical acrylic acid class thickener of monomer residue, and the medical acrylic acid class thickener prepared using the method.
Description
Technical field
The present invention relates to thickener field, particularly a kind of medical acrylic acid class thickener and preparation method thereof.
Background technology
Medical acrylic acid class thickener is widely used in gel preparation, such as the ointment for external application and for taking orally
Fluid preparation such as slop, monomer residue is less when this requires acrylic thickener in medical field.
In this area, monomer residue is mostly from polymerization temperature, post-processing temperature, the choosing for triggering system in reducing polymer
Select, the selection aspect of emulsification system is set about, and product is improved by high temperature, redox initiation system and microemulsified systems
Monomer residue.
In order to solve the problems, such as monomer residue, Chinese patent ZL201210165229.1 discloses a kind of low monomer residue third
The preparation method of the ester modified waterborne polyurethane pressure-sensitive adhesives of olefin(e) acid, belongs to adhesive technical field.1) using homemade hydroxyl
Acrylate quasi-oligomer replaces acrylic ester monomer modified aqueous polyurethane, makes acrylate that grafting occur with polyurethane anti-
Should, then network structure is formed by cross-linking agents, reaction more fully, realizes that monomer is residual compared with acrylic ester monomer is modified
Allowance is low, preparation process is simple, the purpose of energy-conserving and environment-protective；2) product is post-processed using redox initiation system, is entered
One step reduction level of residual monomers, obtains the green adhesive products of ultralow monomer residue；The program uses acrylic monomers with low
The form of polymers is added in reaction system, and uses redox initiation system to control the monomer residue of reaction system.But
It is that for the acrylic thickener of medical grade, shadow can be produced to the viscosity of product and light transmittance using acrylic acid oligomer
Ring.
Chinese patent ZL98811506.9 is disclosed one kind and is produced with low residual by acrylic acid and/or acrylic acid derivative
The method for staying the water solubility or water-swellable polymer product of content of monomer, the method is characterized in that, by nitrogen-containing compound plus
Enter in the monomer solution to be polymerized, and then polymer is heated at a temperature of 120-240 DEG C.The polymerization produce for being produced
Thing is suitable as flocculant, dispersant and absorbent.Monomer residual can be controlled in below 10ppm, and the program is solved well
The problem of the monomer residue determined in polymer, but the new problem brought is that nitrogen compound brings not for polymer
The performance of the aspects such as the too high color that can influence product of medical-risk and heating-up temperature, the viscosity of determination.
Chinese patent ZL2011800254110 discloses a kind of for removing residual monomer from water-absorbing polymeric particles
Method, wherein water-absorbing polymeric particles in the mixer equipped with rotary mixing tool at a temperature of at least 60 DEG C in water
Heat treatment is carried out in the presence of steam.It is included in the mixer equipped with rotary mixing tool the heat treatment in the presence of air-flow
Water-absorbing polymeric particles, temperature of the water-absorbing polymeric particles during heat treatment is at least 60 DEG C and water capacity
It is at least 3 weight %, and the air-flow contains at least 0.01kg vapor per kg dry gas.The program has more outstanding
Residue removal effect, but the problem deposited is, and traditional acrylic thickener is powder, in the air-flow containing vapor
In easily reunite agglomerating, the use for the later stage is very inconvenient.
Therefore, be directed to for acrylic thickener, the change of Study Polymer Melts structure, and post processing it is corresponding
Adjust meaning of the influence to monomer residue with more practicality.
The content of the invention
The present invention is intended to provide a kind of preparation method of the few medical acrylic acid class thickener of monomer residue, and use should
The medical acrylic acid class thickener that method is prepared.
Its concrete scheme is：A kind of preparation method of medical acrylic acid class thickener, comprises the following steps：
Step 1：Under nitrogen protection, to the first monomer, solvent, dispersant is added in reactor, stir and be warming up to 55
~80 DEG C；The first described monomer is made up of unsaturated carboxylic acid monomer and sucrose base allyl ether series crosslinking agent, sucrose base allyl
The weight of base ethers crosslinking agent accounts for the 1.0~1.2% of the first total weight of monomer；
Step 2：To the initiator for adding 15~20wt% in the reactor of step 1 in the way of being added dropwise respectively, during dropwise addition
Between be 0.5~1 hour；Then second comonomer and remaining initiator are added in the way of being added dropwise, is reacted 2~6 hours；Described
Polyalkenyl ether of the second comonomer by unsaturated carboxylic acid monomer and with two or three polymerizable ethylenical unsaturated double bonds；Institute
The weight of the polyalkenyl ether stated accounts for the 0.4~0.8% of second comonomer weight；
The first described monomer and the weight ratio of second comonomer are 1:3~4；
Step 3：And again disperse sediment with solvent after being washed for several times with solvent；
Step 4：The mixture of step 3 is dried in the form of being spray-dried, dried dust is collected and is obtained final product.
In the preparation method of above-mentioned medical acrylic acid class thickener, in described step 4, the charging speed of spray drying
It is 10-20ml/min to spend, and EAT is 110~145 DEG C；Leaving air temp is 50-90 DEG C, and atomizing pressure is 0.3-0.7Mpa,
Carrier gas is inert gas.
Preferably, first sediment is washed with the solvent of 1-2 times equivalent to the first monomer and second comonomer gross weight in step 4
Wash, then disperseed with the solvent of 2-4 times equivalent to the first monomer and second comonomer gross weight.
In the preparation method of above-mentioned medical acrylic acid class thickener, described unsaturated carboxylic acid monomer is acrylic acid,
One or more in methacrylic acid, crotonic acid, maleic acid, fumaric acid, itaconic acid of combination.
In the preparation method of above-mentioned medical acrylic acid class thickener, step 1, the solvent described in 3 are independently selected
One or more combination from benzene, toluene, hexamethylene, ethyl acetate, dichloromethane, dichloroethanes, in described step 1
Solvent load is 5-8 times of the first monomer and second comonomer gross weight.
In the preparation method of above-mentioned medical acrylic acid class thickener, initiator is benzoyl peroxide, peroxidating month
Osmanthus acyl, acetyl peroxide cyclohexylsulfonyl, the new certain herbaceous plants with big flowers acid α-isopropyl phenyl ester of peroxidating, the new certain herbaceous plants with big flowers acid -1,1- dimethyl -3- hydroxyls of peroxidating
Base butyl ester, peroxy dicarbonate two (3- methoxybutyls), the di-isopropyl peroxydicarbonate, (2- of peroxy dicarbonate two
Octyl Nitrite), the new enanthic acid α-isopropyl phenyl ester of peroxidating, peroxy dicarbonate di-n-propyl ester, in new peroxide tert-butyl caprate
One or more combination, the weight of described initiator equivalent to the first monomer and second comonomer gross weight 0.1%~
0.8%.
In the preparation method of above-mentioned medical acrylic acid class thickener, described dispersant is sorbitan fatty
Acid esters, polyglyceryl fatty acid ester, sucrose fatty ester, alkylbenzenesulfonate, polyoxyethylene fatty acid ester, polyoxyethylene alkyl ether
One or more combination of sulfonate weight, described dispersant weight is equivalent to the first monomer and the 0.3- of second comonomer gross weight
1.0%.
In the preparation method of above-mentioned medical acrylic acid class thickener, two or three described polymerizable olefinics are not
The polyalkenyl ether of saturation double bond is pentaerythritol diallyl ether, pentaerythritol triallyl ether, trimethylolpropane diene
One or more mixing in propyl ether, trimethylolpropane tris allyl ether.
Described sucrose base allyl ether series crosslinking agent is sucrose diallyl ether, sucrose triallyl ether.
Meanwhile, the invention also discloses a kind of medical acrylic acid class thickener, prepared by method described above.
The beneficial effects of the present invention are：
The present invention carries out pre-polymerization using partial monosomy first, and the crosslinking agent that the pre-polymerization is used is handed over for sucrose base allyl ether series
Connection agent, sucrose base allyl ether series crosslinking agent, due to its architectural characteristic, can be crosslinked its stratum nucleare equal in the preparation process of stratum nucleare
Even property is improved, in the case of certain consumption, beneficial to the particulate porous gap structure in later stage decompression spray process
Formed, improve the degree of volatility of solvent and monomer, specifically, sucrose base allyl ether series crosslinking agent is due to being with disaccharides structure
Based on its have its crosslink density in the case of five yuan, hexa-atomic oxygen heterocycle, same amount be less than other crosslinking agents, when by
When environmental pressure is plummeted to low pressure by high pressure, the hole formation to the network structure of stratum nucleare is favourable.The crosslinking agent of shell can
To carry out the selection of diversification, it is preferred that being the crosslinking agent and trimethylolpropane class crosslinking agent of Pentaerythritols, the type
Crosslinking agent be favourable for the intensity of shell, prevent when environmental pressure is plummeted to low pressure by high pressure, polymer molecule knot
The deterioration of viscosity and light transmittance caused by structure destruction.
Above-mentioned polymer is for the contribution that residual monomer is removed, poly- in particle when unexpected decompression operation is carried out
Polymeric network can uniform diastole, beneficial to the quick effusion of solvent in particle, and then take away what is remained in the solvent of quick volatilization
Monomer, making the monomer residue of product significantly reduces to ppm ranks.
Specific embodiment
With reference to specific embodiment, technical scheme is described in further detail, but do not constitute it is right
Any limitation of the invention.
In order to more clearly the present invention will be described, it is listed below embodiment to illustrate superiority of the invention.
Embodiment 1
Step 1：Under nitrogen protection, to addition 25g first monomers, 500g ethyl acetate and hexamethylene in four-hole boiling flask
(mass ratio of ethyl acetate and hexamethylene is 4：1), 0.5g sorbitan fatty esters, stir and are warming up to 65 DEG C；Institute
The first monomer stated is made up of acrylic acid and 0.28g sucrose diallyl ethers；
Step 2：The peroxidating for accounting for initiator total amount 16wt% is added in the reactor of step 1 in the way of being added dropwise respectively
The neodecanoic acid tert-butyl ester (gross weight of used initiator is 0.5g in this step 2), time for adding is 0.5 hour；Then with drop
Plus mode add 75g second comonomers and remaining new peroxide tert-butyl caprate, time for adding is 6 hours；Described second
Monomer is made up of acrylic acid and 0.38g pentaerythritol diallyl ethers；Reaction temperature in this step is 60 DEG C.
Step 3：Reaction terminates rear suction filtration, and (mass ratio of ethyl acetate and hexamethylene is with ethyl acetate and hexamethylene
4：1) wash 3 times, each cleaning solvent consumption is 40g, collects filter residue；
Step 4：To 400g ethyl acetate and hexamethylene is added in filter residue, (mass ratio of ethyl acetate and hexamethylene is 4：
1), stir 2 hours；
Step 5：To be dried in the form of being spray-dried after the mixture stirring of step 4, collect dried dust
Obtain final product；The equipment of spray drying is the small spraying drying instrument B-290 of BUCHI Laboratory Instruments company of Switzerland, and charging rate is
20ml/min, EAT is 125 DEG C；Leaving air temp is 80 DEG C, and atomizing pressure is 0.7Mpa, and carrier gas is inert gas.
Embodiment 2
Step 1：Under nitrogen protection, to addition 20g first monomers, 700g ethyl acetate and hexamethylene in four-hole boiling flask
(mass ratio of ethyl acetate and hexamethylene is 1：2), 1g sucrose fatty esters, stir and are warming up to 80 DEG C；Described first is single
Body is made up of acrylic acid and 0.24g sucrose triallyl ethers；
Step 2：To (the 3- of peroxy dicarbonate two for adding 20wt% in the reactor of step 1 in the way of being added dropwise respectively
Methoxybutyl) (gross weight of used initiator is 0.8g in this step 2), time for adding is 1 hour；Then with dropwise addition
Mode adds 80g second comonomers and remaining peroxy dicarbonate two (3- methoxybutyls), and time for adding is 4 hours；It is described
Second comonomer be made up of acrylic acid and 0.32g trimethylolpropane allyl ethers；Reaction temperature in this step is 80 DEG C.
Step 3：Reaction terminates rear suction filtration, and (mass ratio of ethyl acetate and hexamethylene is with ethyl acetate and hexamethylene
1：2) wash 3 times, each cleaning solvent consumption is 60g, collects filter residue；
Step 4：To 200g ethyl acetate and hexamethylene is added in filter residue, (mass ratio of ethyl acetate and hexamethylene is 1：
2), stir 2 hours；
Step 5：To be dried in the form of being spray-dried after the mixture stirring of step 4, collect dried dust
Obtain final product；The equipment of spray drying is the SD-06 Laboratary type spray-dried instruments of Labplant companies of Britain, and charging rate is
10ml/min, the EAT of spray drying is 120 DEG C, and leaving air temp is 60 DEG C；Atomizing pressure is 0.4Mpa.
Embodiment 3
Step 1：Under nitrogen protection, to addition 22g first monomers, 600g benzene, 0.8g polyoxyethylene fat in four-hole boiling flask
Fat acid esters, stirs and is warming up to 70 DEG C；The first described monomer is made up of acrylic acid and 0.22g sucrose triallyl ethers；
Step 2：To the peroxy dicarbonate two positive third for adding 18wt% in the reactor of step 1 in the way of being added dropwise respectively
Ester (gross weight of used initiator is 0.4g in this step 2), time for adding is 1 hour；Then added in the way of being added dropwise
78g second comonomers and remaining peroxy dicarbonate di-n-propyl ester, time for adding are 5 hours；Described second comonomer is by propylene
Acid and 0.62g pentaerythritol triallyl ethers composition；Reaction temperature in this step is 70 DEG C.
Step 3：Reaction terminates rear suction filtration, and is washed with benzene 3 times, and each cleaning solvent consumption is 50g, collects filter residue；
Step 4：To 300g benzene is added in filter residue, stir 4 hours；
Step 5：To be dried in the form of being spray-dried after the mixture stirring of step 4, collect dried dust
Obtain final product；The equipment of spray drying is the SD-06 Laboratary type spray-dried instruments of Labplant companies of Britain, and charging rate is
15ml/min, the EAT of spray drying is 100 DEG C, and leaving air temp is 70 DEG C；Atomizing pressure is 0.6Mpa.
Embodiment 4
Step 1：Under nitrogen protection, to addition 21g first monomers, 500g ethyl acetate and hexamethylene in four-hole boiling flask
(mass ratio of ethyl acetate and hexamethylene is 1：4), 0.8g polyoxyethylene fatty acid esters, stir and are warming up to 70 DEG C；Described
First monomer is made up of acrylic acid and 0.22g sucrose diallyl ethers；
Step 2：To the peroxy dicarbonate two positive third for adding 18wt% in the reactor of step 1 in the way of being added dropwise respectively
Ester (gross weight of used initiator is 0.4g in this step 2), time for adding is 1 hour；Then added in the way of being added dropwise
78g second comonomers and remaining peroxy dicarbonate di-n-propyl ester, time for adding are 5 hours；Described second comonomer is by propylene
Acid and 0.62g pentaerythritol triallyl ethers composition；
Step 3：Reaction terminates rear suction filtration, and is washed with benzene 3 times, and each cleaning solvent consumption is 50g, collects filter residue；
Step 4：To 300g benzene is added in filter residue, stir 4 hours；
Step 5：To be dried in the form of being spray-dried after the mixture stirring of step 4, collect dried dust
Obtain final product；The equipment of spray drying is the SD-06 Laboratary type spray-dried instruments of Labplant companies of Britain, and charging rate is
15ml/min, the EAT of spray drying is 95 DEG C, and leaving air temp is 70 DEG C；Atomizing pressure is 0.6Mpa.
Embodiment 5
Step 1：Under nitrogen protection, to addition 21g first monomers, 500g ethyl acetate and hexamethylene in four-hole boiling flask
(mass ratio of ethyl acetate and hexamethylene is 1：4), 0.8g polyoxyethylene fatty acid esters, stir and are warming up to 70 DEG C；Described
First monomer is made up of acrylic acid and 0.22g sucrose diallyl ethers；
Step 2：To the peroxy dicarbonate two positive third for adding 18wt% in the reactor of step 1 in the way of being added dropwise respectively
Ester (gross weight of used initiator is 0.4g in this step 2), time for adding is 1 hour；Then added in the way of being added dropwise
78g second comonomers and remaining peroxy dicarbonate di-n-propyl ester, time for adding are 5 hours；Described second comonomer is by propylene
Acid and 0.62g sucrose triallyls ether composition；
Step 3：Reaction terminates rear suction filtration, and is washed with benzene 3 times, and each cleaning solvent consumption is 50g, collects filter residue；
Step 4：To 300g benzene is added in filter residue, stir 4 hours；
Step 5：To be dried in the form of being spray-dried after the mixture stirring of step 4, collect dried dust
Obtain final product；The equipment of spray drying is the small spraying drying instrument B-290 of BUCHI Laboratory Instruments company of Switzerland, and charging rate is
15ml/min, the EAT of spray drying is 90 DEG C, and leaving air temp is 70 DEG C；Atomizing pressure is 0.6Mpa.
Comparative example 1：
10 parts of commercially available cross-linking type agent for polyacrylic acid thickening.
Comparative example 2：
It is substantially the same with embodiment 1, different places are that the first monomer is by acrylic acid and 0.28g trimethylolpropanes
Triallyl ether is constituted.
Comparative example 3：
Step 1：Under nitrogen protection, to addition 20g first monomers, 700g ethyl acetate and hexamethylene in four-hole boiling flask
(mass ratio of ethyl acetate and hexamethylene is 1：2), 1g sucrose fatty esters, stir and are warming up to 80 DEG C；Described first is single
Body is made up of acrylic acid and 0.24g sucrose diallyl ethers；
Step 2：To (the 3- of peroxy dicarbonate two for adding 20wt% in the reactor of step 1 in the way of being added dropwise respectively
Methoxybutyl) (gross weight of used initiator is 0.8g in this step 2), time for adding is 1 hour；Then with dropwise addition
Mode adds 80g second comonomers and remaining peroxy dicarbonate two (3- methoxybutyls), and time for adding is 4 hours；It is described
Second comonomer be made up of acrylic acid and 0.32g trimethylolpropane allyl ethers；
Step 3：Reaction terminates rear suction filtration, and is dried in vacuum drying chamber under conditions of 70 DEG C, in vacuum drying chamber-
0.095Mpa。
Performance test and analysis
Method of testing：
1st, 1% gel viscosity measuring method：
200g deionized waters are weighed in the beaker of 500mL, add product 2g, by beaker be placed under electric blender in
1000rpm is stirred until homogeneous；Then 18wt% sodium hydroxide solutions are used while stirring under the speed of 300rpm, pH value is adjusted
For：6.8~7.3, stir, froth breaking is centrifuged, measure viscosity.
2nd, the measure of light transmittance
Is fitted into partial gel in 1cm cuvettes after one hour by the gel constant temperature 25 DEG C of above-mentioned centrifugation, bottom is then placed in
Centrifuge froth breaking is used in being lined with paper handkerchief (playing cushioning effect) plastic centrifuge tube in portion.Centrifugal rotational speed 3500rmp, time 30min.
With ultraviolet specrophotometer under 420nm, its light transmittance is surveyed.
3rd, monomer residue method of testing：
Scope
The measure of residual acrylic acid level of this standard suitable for acrylic thickener.
Normative reference
The preparation of GB/T602-2002 chemical reagent impurity determination standard liquids
Principle
This method is set up for residual acrylic acid in measure polymer emulsion sample.Polymer samples are in alcoholic solution
Extraction 1.5h~2.0h, extract is by after centrifugation, filtering, dilute with water uses efficient liquid phase chromatographic analysis.The peak area of acquisition
Content is relatively drawn with standard curve.
Determine
Instrument
3.1.1 Agilent high performance liquid chromatographs, VWD detectors, Ezchrom chromatographic work stations；
3.1.2 C185um(150mm*4.6mm)；
3.1.4 the water system of 0.45um, organic system solvent filter film；
3.1.5 the water system sample filter of 0.45um；
3.1.6 ultrasonic cleaner；
3.1.7 pH meter：Scale division value is 0.01pH；
3.1.8 electronic balance：Scale division value is 0.0001g；
3.1.9 magnetic stirring apparatus；
3.1.10 vacuum apparatus；
Routine Test Lab glassware.
3.2 reagents and solution
3.2.1 acrylic acid：AR, mass fraction is more than 98.0%；
3.2.3 methyl alcohol：Chromatographically pure, membrane filtration is filtered using preceding use 0.45um organic systems；
3.2.4 potassium dihydrogen phosphate：AR；
3.2.5 phosphoric acid：AR；
3.2.6 potassium dihydrogen phosphate buffer solution (0.01mol/L)：Weigh the biphosphate of 0.54g (being accurate to 0.001g)
Potassium is in 1000mL beakers, plus 800mL water stirring and dissolving is uniform, and pH value is adjusted to 3 ± 0.1 with SPA, aqueous with band 0.45um
The vacuum apparatus filtering of filter membrane.
3.2.7 the preparation of 1000mg/L Standard Stock solutions：
Precision weighs the acrylic acid standard sample of (0.1 ± 0.001) g (being accurate to 0.0001g) to the volumetric flask of 100mL
In, scale constant volume is slowly diluted to water, concentration is the Standard Stock solutions of 1000mg/L.
3.2.8100mg/L the preparation of standard liquid：
1000mg/L Standard Stock solutions 10mL is pipetted in the volumetric flask of 100mL, scale constant volume, concentration is diluted with water to
It is the Standard Stock solutions of 100mg/L.
3.2.9 the preparation of standard liquid：
It is the Standard Stock solutions of 100mg/L to 5 100mL's to draw 1mL, 5mL, 10mL, 25mL, 50mL concentration respectively
In volumetric flask, scale is added water to, shaken up, the acrylic acid standard of 1mg/L, 5mg/L, 10mg/L, 25mg/L, 50mg/L is made into respectively
Solution.
3.3 liquid phase chromatogram conditions
3.3.1 mobile phase：Jia Chun ︰ potassium dihydrogen phosphate buffer solution=2 ︰ 8；
3.3.2 flow velocity：1.0mL/min；
3.3.3 sample size：20uL；
3.3.4 chromatographic column：C184.6*150mm；
3.3.5 detector wavelength：200nm；
Before experiment starts, high performance liquid chromatograph is started with conditions above, lead to mobile phase until obtaining the baseline of stabilization, so
Sample introduction afterwards.
3.4 analytical procedures
3.4.1 the formulation of standard curve
The acrylic acid standard liquid of 1mg/L, 5mg/L, 10mg/L, 25mg/L, 50mg/L is carried out into liquid chromatogram point respectively
Analysis, measures acrylic acid peak area (the secondary parallel sample introduction of standard specimen), draws the standard curve at acrylic acid peak.
If curve crosses origin, it is also possible to which single-point method is tested.
3.4.2 the preparation of sample
Accurately weigh in (0.2 ± 0.1) g (being accurate to 0.0001g) samples to the polyethylene bottle with cover of 60mL, add
50.00mL methyl alcohol, adds magnet rotor, screws bottle cap, is put into and 2h is stirred on magnetic stirring apparatus.10min is stood, supernatant liquor is turned
Enter in 10mL centrifuge tubes, sealed with preservative film, under 3500r/min, centrifugation 40min.
3.4.3 determine
Pipette in supernatant liquor to the 10mL volumetric flasks of 2.00mL, use water constant volume, shake up, and with 0.45 μm of water system sample
Filter is filtered.This filtrate is taken, after ultrasound (1-2) min, sample introduction carries out liquid-phase chromatographic analysis, draws the chromatogram of residual acrylic acid
Peak area.And its concentration c is found from standard curve.
3.5 calculate：
The mass fraction w1 of residual acrylic acid, numerical value is represented with %, calculated by following equation (1)：
In formula：
C --- the concentration checked on standard curve, mg/L；
M --- sample quality, g.
3.6 points for attention
3.6.1 the degree of fitting of standard curve needs more than >=0.9995, because degree of fitting is higher, the degree of accuracy is higher, therefore such as
Can reach four it is 9 best.
3.6.2 standard curve can be done once with one month, but because standard sample standing time it is more long after, its result can be relatively low,
And standing time result more long is smaller.So needing to carry out single point correction using the solution of existing preparation daily.Single point correction is mainly anticipated
Whether justice is the state for reflecting instrument as state when doing standard curve.If error very little (≤0.1mg/L), can see
It is not changed in as instrument state；If difference religion it is big (>0.1mg/L), please first confirm whether pillar cleans up, instrument set and
Whether the method for use is consistent with former, such as inconsistent, then now instrument is bent with the standard of drafting to the response signal of same concentration
Had any different during line, standard curve need to have been repainted.
3.6.3 the term of validity of acrylic acid Standard Stock solutions is one month.
Test result such as table 1 below：
The viscosity and monomer residue test result of the embodiment 1-3 of table 1 and comparative example 1-3
Can be seen that the present processes by above-mentioned test can effectively improve the monomer in spray-drying process
Eradicating efficacy, significantly reduces the monomer residue in product.
Stratum nucleare crosslinking agent can reduce monomer residue for sucrose base allyl ether series crosslinking agent, and shell monomers are preferably season penta
Tetrol diallyl ether, pentaerythritol triallyl ether, trimethylolpropane allyl ether, trimethylolpropane tris pi-allyl
One or more in ether mixing, the intensity beneficial to shell is improved, and prevents from being caused in spray-drying process viscosity loss and thoroughly
Light rate is lost.
It is above-described be only presently preferred embodiments of the present invention, it is all made in the range of the spirit and principles in the present invention appoint
What modification, equivalent and improvement etc., should be included within the scope of the present invention.
Claims (9)
1. a kind of preparation method of medical acrylic acid class thickener, it is characterised in that comprise the following steps：
Step 1：Under nitrogen protection, to the first monomer, solvent, dispersant is added in reactor, stir and be warming up to 55~80
℃；The first described monomer is handed over by unsaturated carboxylic acid monomer and sucrose base allyl ether series crosslinking agent, sucrose base allyl ether series
The weight for joining agent accounts for the 1.0~1.2% of the first total weight of monomer；
Step 2：To the initiator for adding 15~20wt% in the reactor of step 1 in the way of being added dropwise respectively, time for adding is
0.5~1 hour；Then second comonomer and remaining initiator, isothermal reaction 2~6 hours are added in the way of being added dropwise；Described
Polyalkenyl ether group of the second comonomer by unsaturated carboxylic acid monomer and with two or three polymerizable ethylenical unsaturated double bonds
Into；The weight of described polyalkenyl ether accounts for the 0.4~0.8% of second comonomer weight；
The first described monomer and the weight ratio of second comonomer are 1:3~4；
Step 3：Reaction terminates rear suction filtration, and again disperses sediment with solvent after being washed for several times with solvent；
Step 4：The mixture of step 3 is dried in the form of being spray-dried, dried dust is collected and is obtained final product.
2. the preparation method of medical acrylic acid class thickener according to claim 1, it is characterised in that described step 4
In, the charging rate of spray drying is 10-20ml/min, and EAT is 90~125 DEG C；Leaving air temp is 50-90 DEG C, atomization
Pressure is 0.3-0.7Mpa, and carrier gas is inert gas.
3. the preparation method of medical acrylic acid class thickener according to claim 1, it is characterised in that described unsaturation
Carboxylic acid monomer is the combination of one or more in acrylic acid, methacrylic acid, crotonic acid, maleic acid, fumaric acid, itaconic acid.
4. the preparation method of medical acrylic acid class thickener according to claim 1, it is characterised in that step 1,3, middle institute
The solvent stated is respectively and independently selected from one or more group in benzene, toluene, hexamethylene, ethyl acetate, dichloromethane, dichloroethanes
Close, the solvent load in described step 1 is 5-8 times of the first monomer and second comonomer gross weight.
5. the preparation method of medical acrylic acid class thickener according to claim 1, it is characterised in that initiator is peroxide
Change benzoyl, lauroyl peroxide, acetyl peroxide cyclohexylsulfonyl, the new certain herbaceous plants with big flowers acid α-isopropyl phenyl ester of peroxidating, the new certain herbaceous plants with big flowers of peroxidating
Acid -1,1- dimethyl -3- hydroxybutyls ester, peroxy dicarbonate two (3- methoxybutyls), di-isopropyl peroxydicarbonate,
Peroxy dicarbonate two (2- Octyl Nitrites), the new enanthic acid α-isopropyl phenyl ester of peroxidating, peroxy dicarbonate di-n-propyl ester, peroxidating
One or more combination in the neodecanoic acid tert-butyl ester, the weight of described initiator is equivalent to the first monomer and second comonomer
The 0.1%~0.8% of gross weight.
6. the preparation method of medical acrylic acid class thickener according to claim 1, it is characterised in that described dispersant
It is sorbitan fatty ester, polyglyceryl fatty acid ester, sucrose fatty ester, alkylbenzenesulfonate, Polyoxyethylene fatty
Acid esters, one or more of polyoxyethylene alkyl ether sulfonate weight combination, described dispersant weight equivalent to the first monomer and
The 0.3-1.0% of second comonomer gross weight.
7. the preparation method of medical acrylic acid class thickener according to claim 1, it is characterised in that described two or
Three polyalkenyl ethers of polymerizable ethylenical unsaturated double bonds are pentaerythritol diallyl ether, pentaerythrite triallyl
One or more mixing in ether, trimethylolpropane allyl ether, trimethylolpropane tris allyl ether.
8. the preparation method of medical acrylic acid class thickener according to claim 1, it is characterised in that described sucrose base
Allyl ether series crosslinking agent is sucrose diallyl ether, sucrose triallyl ether.
9. a kind of medical acrylic acid class thickener, it is characterised in that be prepared into by the method as described in claim 1-8 is any
Arrive.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108670159A (en) * | 2018-06-06 | 2018-10-19 | 浙江大学 | Split cup automatic cleaning system based on ul-trasonic irradiation |
| CN111440580A (en) * | 2020-04-23 | 2020-07-24 | 东莞市中凌包装材料有限公司 | Aqueous APAO-based disposable medical packaging hot melt adhesive and preparation process thereof |
| CN112538142A (en) * | 2020-11-24 | 2021-03-23 | 贵州省欣紫鸿药用辅料有限公司 | Preparation method and application of thickening polymer |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103153277A (en) * | 2010-09-02 | 2013-06-12 | 路博润高级材料公司 | Polymers and compositions |
| CN104861104A (en) * | 2015-06-08 | 2015-08-26 | 广州天赐高新材料股份有限公司 | Quick-wetting carboxylic acid copolymer thickening agent and preparation method thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103153277A (en) * | 2010-09-02 | 2013-06-12 | 路博润高级材料公司 | Polymers and compositions |
| CN104861104A (en) * | 2015-06-08 | 2015-08-26 | 广州天赐高新材料股份有限公司 | Quick-wetting carboxylic acid copolymer thickening agent and preparation method thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108670159A (en) * | 2018-06-06 | 2018-10-19 | 浙江大学 | Split cup automatic cleaning system based on ul-trasonic irradiation |
| CN108670159B (en) * | 2018-06-06 | 2020-06-23 | 浙江大学 | Separation type cup automatic cleaning system based on ultrasonic action |
| CN111440580A (en) * | 2020-04-23 | 2020-07-24 | 东莞市中凌包装材料有限公司 | Aqueous APAO-based disposable medical packaging hot melt adhesive and preparation process thereof |
| CN112538142A (en) * | 2020-11-24 | 2021-03-23 | 贵州省欣紫鸿药用辅料有限公司 | Preparation method and application of thickening polymer |
| CN112538142B (en) * | 2020-11-24 | 2023-03-24 | 贵州省欣紫鸿药用辅料有限公司 | Preparation method and application of thickening polymer |
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