CN1895258A - Diflunisal slow-releasing preparation and its making method - Google Patents
Diflunisal slow-releasing preparation and its making method Download PDFInfo
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- CN1895258A CN1895258A CN 200610052155 CN200610052155A CN1895258A CN 1895258 A CN1895258 A CN 1895258A CN 200610052155 CN200610052155 CN 200610052155 CN 200610052155 A CN200610052155 A CN 200610052155A CN 1895258 A CN1895258 A CN 1895258A
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- diflunisal
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- releasing agent
- slow releasing
- pure water
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- 229960000616 diflunisal Drugs 0.000 title claims abstract description 49
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims description 16
- 239000013078 crystal Substances 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- 239000000243 solution Substances 0.000 claims description 35
- 239000003795 chemical substances by application Substances 0.000 claims description 31
- 239000000126 substance Substances 0.000 claims description 19
- 229910002651 NO3 Inorganic materials 0.000 claims description 16
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 238000013019 agitation Methods 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 229910052599 brucite Inorganic materials 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 239000011261 inert gas Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 150000001450 anions Chemical class 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- -1 diflunisal anion Chemical class 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 150000001449 anionic compounds Chemical class 0.000 claims description 2
- 229910001412 inorganic anion Inorganic materials 0.000 claims description 2
- 238000009830 intercalation Methods 0.000 claims description 2
- 230000002687 intercalation Effects 0.000 claims description 2
- 239000002648 laminated material Substances 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 abstract description 5
- 229960001545 hydrotalcite Drugs 0.000 abstract description 5
- 229910001701 hydrotalcite Inorganic materials 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 5
- 125000000129 anionic group Chemical group 0.000 abstract description 2
- 230000000146 antalgic effect Effects 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 12
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 12
- 239000008367 deionised water Substances 0.000 description 11
- 229910021641 deionized water Inorganic materials 0.000 description 11
- 239000003814 drug Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 230000000202 analgesic effect Effects 0.000 description 6
- 238000007086 side reaction Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 238000011160 research Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- VNZCGWSZJOIBAK-ACGXKRRESA-N (2s)-2-[[4-[1-(2-amino-4-oxo-1h-pteridin-6-yl)ethylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1C(C)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VNZCGWSZJOIBAK-ACGXKRRESA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 230000001458 anti-acid effect Effects 0.000 description 2
- 239000008366 buffered solution Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000011229 interlayer Substances 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 238000011175 product filtration Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A slow-releasing diflunisal with high anti-inflammatory and antalgic effect and its preparing process are disclosed. It uses the anionic laminar hydrotalcite as its main body and has the intercalated hydrotalcite crystal structure.
Description
(1) technical field
The present invention relates to slow releasing agent of a kind of NSAID (non-steroidal anti-inflammatory drug) and preparation method thereof, particularly a kind of diflunisal slow releasing agent and preparation method thereof.
(2) background technology
Non_steroidal anti_inflammatory drug (NSAIDs) has antiinflammatory, rheumatism, pain relieving, bring down a fever and effect such as anticoagulation, is widely used in the alleviation of osteoarthritis, rheumatoid arthritis, multiple heating and various pain symptoms clinically.NSAIDs is that one of maximum medicament categories is used in the whole world at present.The whole world has 3,000 ten thousand people using about every day.But treatment also brings some side reactions, serious entail dangers to people's life simultaneously.Therefore, along with increasing that NSAIDs uses, the safe handling problem of this class medicine also more and more receives the concern of clinicist, pharmacist, patient, society and government.The side reaction that reduces this type of medicine promptly becomes the hot issue of research.
Use one of them method that reduces its side reaction in the anti-anti-inflammatory analgesic of non-steroidal (NSAIDs) process to be and the coupling of acid-resisting material, therefore, exploitation acid-resisting medicinal slow release agent just becomes focus.As everyone knows, brucite has stronger antiacid effect, so can be used as antacid and NSAIDs coupling.Discover that simultaneously because the interlayer anion of brucite has interchangeability, the hydrotalcite layers anion can exchange with various aniones.Contain on its laminate than the strong basicity position, can introduce some organic acidity groups, the inorganic-organic composite material that obtains having special nature and function.Along with going deep into of this area research, brucite more and more is subjected to people's attention in the application aspect medicinal slow release agent (particularly non_steroidal anti_inflammatory drug) in recent years.There are some researches show, can reduce this medicine to duodenal infringement after NSAIDs and brucite are compound, improve the dissolubility of NSAIDs, even can also alleviate its stimulation stomach.People such as Choy (Choy J H., Jung J S., Oh J M., etal.Biomaterials, 2004,25 (15): 3059～3064) adopt ion exchange that 9-methylpteroylglutamic acid (MTX) is inserted the LDHs interlayer, expectation reaches the controllable sustained-release of MTX, found that synthetic product is more much better than than MTX to the inhibitory action of pathogenic bacteria.
At present, the research to the diflunisal slow releasing agent yet there are no report.Diflunisal is as a kind of novel non_steroidal anti_inflammatory drug, and advantage such as have antiinflammatory, analgesic activity is strong, and untoward reaction is few is compared curative effect with similar anti-anti-inflammatory analgesic (as ibuprofen, aspirin) and will be got well.Therefore, diflunisal is inserted hydrotalcite layers becomes a kind of medicinal slow release agent, can improve its antiinflammatory, analgesic activity, can reduce the side reaction that medicine brings again, can be described as and kills two birds with one stone, to having great importance on the diseases such as treatment rheumatism.
(3) summary of the invention
The purpose of this invention is to provide and a kind ofly can improve medicine antiinflammatory, analgesic activity, can reduce diflunisal slow releasing agent of medicine side reaction and preparation method thereof again.
The technical solution adopted in the present invention is as follows:
A kind of diflunisal slow releasing agent is based on the anion laminated material brucite, and diflunisal is the intercalated houghite crystal structure of intercalation object, and chemical composition is:
(M
2+)
1-x(M
3+)
x(OH)
2(Dif)
a(B
n-)
b·m?H
2O
M wherein
2+Be Mg
2+, Zn
2+, Cu
2+, Ni
2+, Co
2+, Mn
2+In a kind of, M
3+Be Al
3+, Fe
3+, Cr
3+In a kind of, Dif represents diflunisal anion, B
N-Be that electric charge is the inorganic anion of n, a=0.1～1, x=M
3+/ (M
2++ M
3+), 0＜x＜1, x: a=1～3: 1, b=0～1 and satisfy x=a+nb, m and n are positive number.
Further, the M described in the chemical formula
2+Preferred Mg
2+, Zn
2+In a kind of, described M
3+Preferred Al
3+, described B
N-Be NO
3 -, the scope of described x is 0.2＜x＜0.5, x: a recommended 1: 1.
The present invention also provides the method for two kinds of described diflunisal slow releasing agents of different preparations.A kind of is coprecipitation, and step is as follows:
A. with M
2+, M
3+Nitrate compare M by amount of substance
2+/ M
3+Be dissolved in 5 part pure water, with M at=1～5: 1
2+, M
3+Nitrate quality and be 1 part of meter, wiring solution-forming A;
B. get the diflunisal solid and be dissolved in 10～20 parts of pure water, the amount of diflunisal is M
3+1～3 times of nitrate amount of substance, regulator solution are alkalescence, mixing material B;
C. logical inert gas shielding under agitation, splashes in the solution B solution A in 50～80 ℃ of reactions 40～60 hours, filters, and the Cake Wash after drying promptly gets described diflunisal slow releasing agent.
Described noble gas refers to the gas of energy secluding air, recommends to use nitrogen.
Concrete, described coprecipitation is carried out as follows:
A. with M
2+, M
3+Nitrate compares M by amount of substance
2+/ M
3+Be dissolved in 5 part pure water wiring solution-forming A at=1～5: 1;
The amount of b. getting diflunisal is M
3+1 times of the nitrate amount of substance is dissolved in 15 parts of pure water, and regulating pH value with NaOH solution is 10, gets mixing material B;
C. under the strong agitation, solution A is splashed in the solution B N
2Protection, 65 ℃ of reaction 48h.Product filters, and is dry in the Cake Wash final vacuum, promptly gets described diflunisal slow releasing agent.
The present invention also provides a kind of ion exchange to prepare the method for diflunisal slow releasing agent, and step is as follows:
A. with M
2+, M
3+Nitrate compares M by amount of substance
2+/ M
3+Be dissolved in 5 part pure water, with M at=1～5: 1
2+, M
3+Nitrate quality and be 1 part of meter obtains solution A;
B. get alkali metal hydroxide and be dissolved in the pure water, obtain the aqueous slkali that concentration is 1～3mol/L
C; Described alkali metal hydroxide is a kind of among NaOH, the KOH.
C. inert gas shielding under strong agitation, is added drop-wise to solution A, solution C in 5 parts of pure water simultaneously simultaneously, keep the solution pH value between 9～10, abundant mixing, the serosity that obtains is in 50～70 ℃ of following crystallization 15～20h, filter, Cake Wash is to neutral after drying;
D. the amount of getting is M
3+The diflunisal solid that the nitrate amount of substance is 2～3 times is dissolved in 15 parts of pure water, wiring solution-forming D;
E. the product of getting step c is dissolved in 50 parts of pure water, wiring solution-forming E;
F. fully stir down, mixed solution D and E, regulating pH is 8～11, under the inert gas shielding, 50～70 ℃ of reaction 40～50h keep PH constant in the reaction, filter, and with filtration cakes torrefaction, promptly get described diflunisal slow releasing agent after the washing.
Concrete, the method is carried out according to following steps:
A. with M
2+, M
3+Nitrate compares M by amount of substance
2+/ M
3+Be dissolved in 5 part pure water at=1～5: 1, obtains solution A;
B. get the NaOH solid and be dissolved in the pure water, obtaining concentration is the aqueous slkali C of 2mol/L;
C. nitrogen protection; under agitation solution A, solution C are added drop-wise to simultaneously in 5 parts of pure water; the control rate of addition is regulated pH value between 9～10, drips the back and continues to stir, fully mixing; the serosity that obtains is in 60～70 ℃ of following crystallization 15～20h; filter, filter cake washs to neutrality with pure water, and 60～70 ℃ dry down; grind, weigh, be stored in the exsiccator.
D. getting amount of substance is M
3+The diflunisal solid that the nitrate amount of substance is 3 times is dissolved in 15 parts of pure water, wiring solution-forming D;
E. the product of getting step c is dissolved in 50 parts of pure water, wiring solution-forming E;
F. fully stir down, mixed solution D and E, regulating pH is 8～11, logical nitrogen protection, 65 ℃ of reaction 48h keep pH constant in the reaction, filter, and with the filter cake vacuum drying, promptly get described diflunisal slow releasing agent after the washing.
Pure water described in the preparation method of aforesaid diflunisal slow releasing agent is a redistilled water.
In above-mentioned preparation method, change the amount of substance or the mixed proportion of obtain solution, all be fine as long as can obtain meeting the end product of structural formula proportionate relationship.
The present invention inserts hydrotalcite layers with diflunisal, and the diflunisal slow releasing agent that obtains is a supramolecular structure, and diflunisal anion and brucite are not compound simply, but bonded by the interaction force between the Subjective and Objective.By adjusting the M in the reaction condition
2+, M
3+Type, M
2+/ M
3+Ratio, hold the factors such as medium of anionic amount of body and release, can realize control to diflunisal-hydrotalcite structure, composition, burst size, rate of release etc.
The present invention is directed to diflunisal a kind of slow releasing agent is provided, not only improved medicine antiinflammatory, analgesic activity, also reduce the side reaction of medicine, have the using value on the industry.
(4) description of drawings:
Fig. 1 is the X-ray powder diffraction figure of the Dif-LDHs of embodiment 2 preparations, and as seen from Figure 1, Dif-LDHs has the crystal structure of houghite material.
Fig. 2 is the supramolecular structured composition of the Dif-LDHs of embodiment 1, example 2 preparations.
Fig. 3 is the Dif-LDHs of embodiment 1, the example 2 preparations release profiles of (pH=7.4) in the mixed phosphate salt buffer solution.
(5) specific embodiment:
Below with specific embodiment technical scheme of the present invention is described, but protection scope of the present invention is not limited thereto:
Embodiment 1
Get 1.53g (6mmol) Mg (NO
3)
26H
2O and 0.75g (2mmol) Al (NO
3)
39H
2O is dissolved in the 10mL deionized water, stir make its dissolve mixing material A; Get 1.79g (6mmol) diflunisal (full name diflunisal is called for short Dif) and be dissolved in the 30mL deionized water, regulating pH value with the NaOH solution of 2mol/L is 10, gets mixing material B.Under the strong agitation, solution A is splashed in the solution B N
2Protection, 65 ℃ of reaction 48h.Dry in product filtration, the Cake Wash final vacuum.Employed deionized water is redistilled water in the process.
According to sign, the chemical composition of the Dif-LDHs that obtains is: Mg
0.70Al
0.30(OH)
2(Dif)
0.300.70H
2O, wherein the content of diflunisal is 49.7%.
Embodiment 2
(1) gets 11.88g (0.04mol) Zn (NO
3)
26H
2O and 7.5gAl (NO
3)
39H
2O (0.02mol) is dissolved in the 100mL deionized water, wiring solution-forming A; Get 4.8g NaOH solid again and be dissolved in the appropriate amount of deionized water, be made into the 2mol/L solution C; N
2Protection is added drop-wise to solution A, solution C in the 100ml deionized water with certain speed that oozes down, and the pH value that remains solution drips the back and continues to stir half an hour between 9～10.Behind 65 ℃ of following crystallization 18h, sucking filtration,, grinds, weighs 65 ℃ of dryings to neutral with deionized water wash, is stored in the exsiccator with the serosity that obtains.Note is made LDHs-NO
3 -
(2) get 1.79g (6mmol) Dif and be dissolved in the 30mL deionized water and get solution D, get 1gLDHs-NO again
3Be dissolved in the 50mL deionized water and get solution E, fully stir down, D and E two solution are mixed, regulate pH=10, strong agitation, N
2Protection, 65 ℃ of reaction 48h.PH value remains unchanged in the reaction.Product after filtration, dry in the Cake Wash final vacuum.
The equal redistilled water of employed deionized water in the process.
According to sign, the chemical composition of the Dif-LDHs that obtains is: Zn
0.70Al
0.30(OH)
2(Dif)
0.21(NO
3)
0.091.2H
2O, wherein the content of diflunisal is 39.5%.
Embodiment 3～4
Press the method for embodiment 2, change the pH value among the embodiment 2 (2), be respectively 9,11, other are operated with embodiment 2.Employed deionized water is redistilled water in the process.
Found that pH value is at 10 o'clock, the crystal structure of the Dif-LDHs material that obtains is better, and represents the d of interlamellar spacing
003Maximum.Concrete XRD data are as follows: pH=9, d
003=1.91nm; PH=10, d
003=1.96nm; PH=11, d
003=1.84nm.
Embodiment 5 effect embodiment
Get each 50mg of Dif-LDHs of embodiment 1, example 2 preparations, drop into respectively (pH=7.4) in the 200mL phosphate buffered solution, 37 ± 0.5 ℃ of following strong agitation discharge 12 hours.From solution, draw the solution of 5mL at set intervals, measure the wherein content of Dif, replenish the phosphate buffered solution of equal volume simultaneously.The content of Dif uses ultraviolet spectrophotometry to measure at 315 ± 1nm place, goes out the release percentage ratio of different time according to the Dif cubage of mensuration, also can be described as release.
Concrete release performance is seen accompanying drawing 3.
Claims (10)
1. a diflunisal slow releasing agent is characterized in that described slow releasing agent is based on the anion laminated material brucite, and diflunisal is the intercalated houghite crystal structure of intercalation object, and chemical composition is:
(M
2+)
1-x(M
3+)
x(OH)
2(Dif)
a(B
n-)
b·m?H
2O
M wherein
2+Be Mg
2+, Zn
2+, Cu
2+, Ni
2+, Co
2+, Mn
2+In a kind of, M
3+Be Al
3+, Fe
3+, Cr
3+In a kind of, Dif represents diflunisal anion, B
N-Be that electric charge is the inorganic anion of n, a=0.1～1, x=M
3+/ (M
2++ M
3+), 0＜x＜1, x: a=1～3: 1, b=0～1 and satisfy x=a+nb, m and n are positive number.
2. diflunisal slow releasing agent as claimed in claim 1 is characterized in that described M
2+Be Mg
2+, Zn
2+In a kind of.
3. diflunisal slow releasing agent as claimed in claim 1 is characterized in that described M
3+Be Al
3+
4. diflunisal slow releasing agent as claimed in claim 1 is characterized in that described B
N-Be NO
3 -
5. diflunisal slow releasing agent as claimed in claim 1, the scope that it is characterized in that described x is 0.2＜x＜0.5.
6. diflunisal slow releasing agent as claimed in claim 1 is characterized in that described x: a=1: 1.
7. the preparation method of a diflunisal slow releasing agent as claimed in claim 1 is characterized in that described method step is as follows:
A. with M
2+, M
3+Nitrate compare M by amount of substance
2+/ M
3+Be dissolved in 5 part pure water, with M at=1～5: 1
2+, M
3+The quality summation of nitrate be 1 part of meter, wiring solution-forming A;
B. get the diflunisal solid and be dissolved in 10～20 parts of pure water, the amount of diflunisal is M
3+1～3 times of nitrate amount of substance, regulator solution are alkalescence, mixing material B;
C. logical inert gas shielding under agitation, splashes in the solution B solution A in 50～80 ℃ of reactions 40～60 hours, filters, and the Cake Wash after drying promptly gets described diflunisal slow releasing agent.
8. the preparation method of diflunisal slow releasing agent as claimed in claim 7 is characterized in that in the described method that regulator solution PH is 9-11 among the step b.
9. the preparation method of a diflunisal slow releasing agent as claimed in claim 1 is characterized in that described method step is as follows:
A. with M
2+, M
3+Nitrate compares M by amount of substance
2+/ M
3+Be dissolved in 5 part pure water, with M at=1～5: 1
2+, M
3+The quality summation of nitrate be 1 part of meter, obtain solution A;
B. get alkali metal hydroxide and be dissolved in the pure water, obtaining concentration is the aqueous slkali C of 1～3mol/L;
C. under the inert gas shielding, under agitation solution A, solution C are added drop-wise to simultaneously in 5 parts of pure water, the pH value that keeps solution is between 9～10, and abundant mixing, the serosity that obtains filter in 50～70 ℃ of following crystallization 15～20h, and Cake Wash is to neutral after drying;
D. get the diflunisal solid and be dissolved in 15 parts of pure water, the amount of diflunisal is M
3+2～3 times of nitrate amount of substance, wiring solution-forming D;
E. the product of getting step c is dissolved in 50 parts of pure water, wiring solution-forming E;
F. fully stir down, mixed solution D and E, regulating pH is 8～11, logical inert gas shielding, 50～70 ℃ of reaction 40～50h keep PH constant in the reaction; Filter, the Cake Wash after drying promptly gets described diflunisal slow releasing agent.
10. as the preparation method of the described diflunisal slow releasing agent of one of claim 7～9, it is characterized in that described pure water is a redistilled water.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103127900A (en) * | 2013-03-07 | 2013-06-05 | 清华大学 | Hydrotalcite precursor adsorbent and preparation method thereof |
| CN109758432A (en) * | 2017-11-09 | 2019-05-17 | 郑州泰丰制药有限公司 | A kind of Diflunisal enteric coatel tablets and preparation method thereof |
| CN116196222A (en) * | 2023-02-28 | 2023-06-02 | 上海沐良医疗器械有限公司 | Caries preventing additive, caries preventing material, dental diaphragm and invisible appliance |
-
2006
- 2006-06-27 CN CN 200610052155 patent/CN1895258A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103127900A (en) * | 2013-03-07 | 2013-06-05 | 清华大学 | Hydrotalcite precursor adsorbent and preparation method thereof |
| CN103127900B (en) * | 2013-03-07 | 2015-08-19 | 清华大学 | A kind of Hydrotalcite precursor adsorbent and preparation method thereof |
| CN109758432A (en) * | 2017-11-09 | 2019-05-17 | 郑州泰丰制药有限公司 | A kind of Diflunisal enteric coatel tablets and preparation method thereof |
| CN116196222A (en) * | 2023-02-28 | 2023-06-02 | 上海沐良医疗器械有限公司 | Caries preventing additive, caries preventing material, dental diaphragm and invisible appliance |
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