CN104262138A - 4-biphenylacetic acid and pharmaceutical composition thereof - Google Patents
4-biphenylacetic acid and pharmaceutical composition thereof Download PDFInfo
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- CN104262138A CN104262138A CN201410416465.5A CN201410416465A CN104262138A CN 104262138 A CN104262138 A CN 104262138A CN 201410416465 A CN201410416465 A CN 201410416465A CN 104262138 A CN104262138 A CN 104262138A
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- felbinac
- compound
- recipe quantity
- pharmaceutical composition
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- QRZAKQDHEVVFRX-UHFFFAOYSA-N biphenyl-4-ylacetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1C1=CC=CC=C1 QRZAKQDHEVVFRX-UHFFFAOYSA-N 0.000 title claims abstract description 64
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
- 239000000865 liniment Substances 0.000 claims abstract description 11
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 7
- 239000002674 ointment Substances 0.000 claims abstract description 6
- 239000013078 crystal Substances 0.000 claims abstract description 4
- 239000007924 injection Substances 0.000 claims abstract description 4
- 238000002347 injection Methods 0.000 claims abstract description 4
- 229960000192 felbinac Drugs 0.000 claims description 95
- -1 felbinac compound Chemical class 0.000 claims description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 238000003756 stirring Methods 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 13
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 claims description 11
- 229940040145 liniment Drugs 0.000 claims description 10
- 239000008215 water for injection Substances 0.000 claims description 10
- 239000001433 sodium tartrate Substances 0.000 claims description 9
- 229960002167 sodium tartrate Drugs 0.000 claims description 9
- 235000011004 sodium tartrates Nutrition 0.000 claims description 9
- 239000012065 filter cake Substances 0.000 claims description 8
- 239000002994 raw material Substances 0.000 claims description 7
- 238000003556 assay Methods 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 206010013786 Dry skin Diseases 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 230000008961 swelling Effects 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000011049 filling Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 238000011068 loading method Methods 0.000 claims description 3
- 238000005374 membrane filtration Methods 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims 1
- 230000008018 melting Effects 0.000 claims 1
- 239000006071 cream Substances 0.000 abstract 1
- 239000000499 gel Substances 0.000 abstract 1
- 238000001228 spectrum Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 9
- 239000003814 drug Substances 0.000 description 7
- 238000011835 investigation Methods 0.000 description 5
- 239000000470 constituent Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- NPPJLSILDPVHCM-UHFFFAOYSA-N Felbinac ethyl Chemical group C1=CC(CC(=O)OCC)=CC=C1C1=CC=CC=C1 NPPJLSILDPVHCM-UHFFFAOYSA-N 0.000 description 2
- 206010034464 Periarthritis Diseases 0.000 description 2
- 208000004760 Tenosynovitis Diseases 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000019365 chlortetracycline Nutrition 0.000 description 2
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 2
- 229960001395 fenbufen Drugs 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 206010039361 Sacroiliitis Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to 4-biphenylacetic acid and a pharmaceutical composition thereof. The 4-biphenylacetic acid is in a crystal form. A spectrum measured by X-ray powder diffraction of the 4-biphenylacetic acid has characteristic peaks (2theta +/- 0.2 degree) at 5.8 degrees, 9.6 degrees, 11.7 degrees, 15.0 degrees, 16.3 degrees, 18.9 degrees, 19.4 degrees, 22.1 degrees, 25.2 degrees, 26.8 degrees, 28.5 degrees, 30.3 degrees, 33.2 degrees and 35.5 degrees. The pharmaceutical composition is 4-biphenylacetic acid gel, liniments, ointment, cream or injections which are prepared from the 4-biphenylacetic acid. The prepared 4-biphenylacetic acid is high in purity and good in stability. The pharmaceutical composition is good in stability.
Description
Technical field
The invention belongs to medical art, relate to a kind of felbinac compound and pharmaceutical composition thereof.
Background technology
Felbinac is the medicine that Japanese Lederle [strain] went on the market in 1986 with the exploitation of " Napageln " ointment, and it is a kind of NSAID (non-steroidal anti-inflammatory drug), is effective meta-bolites of fenbufen, the similar fenbufen of its anti-inflammatory activity.Indication is: modification sacroiliitis, scapulohumeral periarthritis, tenosynovitis, peritendinitis, myalgia, wound swelling, pain etc.Meanwhile the Lederle [strain] of Japan develops again the derivative felbinac ethyl of felbinac.Felbinac ethyl is anti-inflammatory analgesic, and in 1989 first in Japan's listing, its preparation is lipomul injection, and after administration, internal metabolism is that felbinac works.Its anti inflammation and heat resolution effect comparatively di-lysine-aspirin is strong, and analgesic activity comparatively pentazocine is strong, and be used for the treatment of rheumatic arthritis, pain in the back, scapulohumeral periarthritis, trauma pain, postoperative pain has good effect, has better effect especially for treatment of cancer pain.
Because the positive therapeutic of felbinac, studying a kind of more stable felbinac compound has active effect for the application of felbinac.The present inventor long-term to a large amount of research process of felbinac in obtain a kind of felbinac compound of crystalline form unexpectedly, this compound has high quality stability, add the security of medication, obviously be better than prior art, work out the felbinac pharmaceutical composition that stability is high simultaneously, be obviously better than prior art.
Summary of the invention
The invention provides a kind of stable felbinac compound.
Felbinac structural formula of compound provided by the invention is as shown in formula I:
Formula I
Described felbinac compound is crystal, adopt X-ray powder diffraction to measure, in its collection of illustrative plates, characteristic peak ° is 5.8 °, 9.6 °, 11.7 °, 15.0 °, 16.3 °, 18.9 °, 19.4 °, 22.1 °, 25.2 °, 26.8 °, 28.5 °, 30.3 °, 33.2 °, 35.5 ° displays in 2 θ ± 0.2.
The X-ray powder diffraction figure of described felbinac compound is shown in Fig. 1.
The fusing point of described felbinac compound is 172 ~ 175 DEG C.
Felbinac compounds process for production thereof of the present invention comprises the steps:
1, by felbinac raw material, volume ratio (g/ml) 1:4 is dissolved in volume ratio is by weight in the methyl alcohol of 8:2 and the mixing solutions of acetone.
2, solution temperature is kept to be 24 ~ 33 DEG C, under the stirring velocity of 130 ~ 150 revs/min, the water and alcohol mixed solution that volume ratio that volume is methyl alcohol in step 1 and acetone mixing solutions 10 ~ 12 times is 9:1 is added while stirring with the solution of 80ml ~ 100ml/min speed in step 1, mixing solutions adds rear stopping and stirring, 2 ~ 4 DEG C are cooled to 0.4 ~ 0.6 DEG C/min speed, leave standstill growing the grain 8 hours, filter, obtain filter cake.
3, will filter the water washing 2 times of the filter cake 2 times of weight obtained in step 2,75 DEG C ~ 80 DEG C dryings 8 hours, namely obtain described felbinac compound.
Felbinac raw material in felbinac preparation of compounds of the present invention is marketable material medicine.
It should be noted that, a kind of formation of crystal formation is subject to the impact of several factors, even if there is very little change in any one factor such as temperature of reaction, time, mixing speed, reactant concn, crystallization condition control just may produce unexpected change, the present inventor experiences a lot of failure in research process, but finally take great effort to study control details, finally obtain felbinac compound of the present invention, each key control point in above preparation of compounds of the present invention is most important to result.
The present invention second object is to provide effective constituent to be the pharmaceutical composition of felbinac compound of the present invention, based on the feature of felbinac prepared by the present invention, felbinac compound the present invention can prepared with existing public technology makes multi-medicament composite preparation, comprise gelifying agent, liniment, ointment, ointment or injection, the invention provides and a kind ofly prepare the splendid felbinac pharmaceutical composition gel of stability and felbinac drug composition liniment based on felbinac compound of the present invention.
Described felbinac pharmaceutical composition gel, specification is 10g:0.3g.
It consists of:
Felbinac compound 30g
Acritamer 940 12g
Sodium hydroxide 18g
Propylene glycol 50g
Poly(oxyethylene glycol) 400 100g
Sodium tartrate 10g
Water for injection 500g
Dehydrated alcohol adds to 1000g
Make 100
Its preparation method is:
1, the sodium tartrate of recipe quantity is dissolved in the water for injection of half recipe quantity, then adds the Acritamer 940 of recipe quantity, fully swelling, stir, make Blank gel;
2, be dissolved in the water for injection of surplus by the sodium hydroxide of recipe quantity, the poly(oxyethylene glycol) 400 of the propylene glycol and recipe quantity that then add recipe quantity stirs, then adds the felbinac of recipe quantity, stirring and dissolving;
3, the liquid in step 2 is slowly added in the Blank gel in step 1, then add dehydrated alcohol to full dose, constantly stir.
4, intermediate after the assay was approved, flexible pipe loading, packs and get final product.
The present inventor surprisingly finds, in the prescription of felbinac gel, add the basis that the sodium tartrate of amount of the present invention and poly(oxyethylene glycol) 400 have very high stability at felbinac compound of the present invention long, can improve the stability of felbinac further.Below test and this illustrated:
The felbinac gel of the different prescription of table 1
| Prescription | 1 | 2 | 3 | 4 |
| Felbinac (g) | 30 | 30 | 30 | 30 |
| Acritamer 940 (g) | 12 | 12 | 12 | 12 |
| Sodium hydroxide (g) | 18 | 18 | 18 | 18 |
| Propylene glycol (g) | 50 | 50 | 50 | 50 |
| Poly(oxyethylene glycol) 400 (g) | — | 100 | — | 100 |
| Sodium tartrate (g) | — | — | 10 | 10 |
| Water for injection (g) | 500 | 500 | 500 | 500 |
| Dehydrated alcohol adds to | 1000g | 1000g | 1000g | 1000g |
Above 4 prescriptions are prepared into by preparation method of the present invention the felbinac gel that specification is 10g:0.3.
The felbinac gel of prescription 1 ~ prescription 4 and commercially available same specification is carried out influence factor test respectively 60 DEG C, high light (4500lx ± 500lx) places 20 days, respectively at sampling calibrating in the 20th day, result compared with 0 day, investigated the stability result of sample and to see the following form 2 ~ table 3.
Table 2 60 DEG C of influence factor test-results
Table 3 high light influence factor test-results
Test-results show effective constituent be felbinac compound prepared by the present invention felbinac gel compared to existing technology stability be significantly increased, the sodium tartrate of amount of the present invention and the conbined usage of poly(oxyethylene glycol) 400, can improve the stability of felbinac gel further.
Described felbinac drug composition liniment, specification is 10ml:0.3g.
It consists of:
Felbinac compound 30g
Dehydrated alcohol adds to 1000ml
Make 100
Its preparation method is:
Be dissolved in the dehydrated alcohol of recipe quantity by the felbinac compound of recipe quantity, 0.22 μm of membrane filtration, intermediate is after the assay was approved, filling, packs and get final product.
accompanying drawing illustrates:
Fig. 1 is the X-ray powder diffraction pattern of felbinac compound prepared by the embodiment of the present invention 1.
Embodiment
The preparation of embodiment 1 felbinac compound
1, felbinac raw material being dissolved in volume ratio is that in the methyl alcohol of 8:2 and the mixing solutions of acetone, the weightmeasurement ratio (g/ml) of felbinac and methyl alcohol and acetone mixing solutions is 1g:4ml.
2, solution temperature in step 1 is kept to be 24 DEG C, under the stirring velocity of 130 revs/min, the water and alcohol mixed solution that volume ratio that volume is methyl alcohol in step 1 and acetone mixing solutions 10 times is 9:1 is added while stirring with the solution of 80ml/min speed in step 1, mixing solutions adds rear stopping and stirring, 2 DEG C are cooled to 0.4 DEG C/min speed, leave standstill growing the grain 8 hours, filter, obtain filter cake.
3, will filter the water washing 2 times of the filter cake 2 times of weight obtained in step 2,75 DEG C of dryings 8 hours, namely obtain described felbinac compound.
X-ray powder diffraction pattern is shown in accompanying drawing 1, and in its collection of illustrative plates, characteristic peak ° is 5.8 °, 9.6 °, 11.7 °, 15.0 °, 16.3 °, 18.9 °, 19.4 °, 22.1 °, 25.2 °, 26.8 °, 28.5 °, 30.3 °, 33.2 °, 35.5 ° displays in 2 θ ± 0.2.Content: 99.97%.Fusing point: 172 ~ 175 DEG C.
The preparation of embodiment 2 felbinac compound
1, felbinac raw material being dissolved in volume ratio is that in the methyl alcohol of 8:2 and the mixing solutions of acetone, the weightmeasurement ratio (g/ml) of felbinac and methyl alcohol and acetone mixing solutions is 1g:4ml.
2, solution temperature in step 1 is kept to be 33 DEG C, under the stirring velocity of 150 revs/min, the water and alcohol mixed solution that volume ratio that volume is methyl alcohol in step 1 and acetone mixing solutions 12 times is 9:1 is added while stirring with the solution of 100ml/min speed in step 1, mixing solutions adds rear stopping and stirring, 4 DEG C are cooled to 0.6 DEG C/min speed, leave standstill growing the grain 8 hours, filter, obtain filter cake.
3, will filter the water washing 2 times of the filter cake 2 times of weight obtained in step 2,80 DEG C of dryings 8 hours, namely obtain described felbinac compound.
X-ray powder diffraction pattern is consistent with embodiment 1.Content: 99.95%.Fusing point: 172 ~ 175 DEG C.
The preparation of embodiment 3 felbinac pharmaceutical composition gel, specification: 10g:0.3g.
Prescription:
Felbinac compound 30g
Acritamer 940 12g
Sodium hydroxide 18g
Propylene glycol 50g
Poly(oxyethylene glycol) 400 100g
Sodium tartrate 10g
Water for injection 500g
Dehydrated alcohol adds to 1000g
Make 100
Its preparation method is:
1, the sodium tartrate of recipe quantity is dissolved in the water for injection of half recipe quantity, then adds the Acritamer 940 of recipe quantity, fully swelling, stir, make Blank gel;
2, be dissolved in the water for injection of surplus by the sodium hydroxide of recipe quantity, the poly(oxyethylene glycol) 400 of the propylene glycol and recipe quantity that then add recipe quantity stirs, then adds the felbinac of recipe quantity, stirring and dissolving;
3, the liquid in step 2 is slowly added in the Blank gel in step 1, then add dehydrated alcohol to full dose, constantly stir.
4, intermediate after the assay was approved, flexible pipe loading, packs and get final product.
The preparation of embodiment 4 felbinac drug composition liniment, specification: 10ml:0.3g.
Prescription:
Felbinac compound 30g
Dehydrated alcohol adds to 1000ml
Make 100
Its preparation method is:
Be dissolved in the dehydrated alcohol of recipe quantity by the felbinac compound of recipe quantity, 0.22 μm of membrane filtration, intermediate is after the assay was approved, filling, packs and get final product.
The invention provides following test and comparing result:
Sample 1: felbinac compound prepared by the embodiment of the present invention 1.
Sample 2: commercially available felbinac raw material.
Sample 3: felbinac gel prepared by the embodiment of the present invention 3.
Sample 4: felbinac gel commercially available product.
Sample 5: the felbinac gel prepared by Chinese patent CN102525904A.
Sample 6: felbinac liniment prepared by the embodiment of the present invention 4.
Sample 7: commercially available felbinac liniment.
Sample 1 is carried out influence factor test respectively 60 DEG C, high light (4500lx ± 500lx) places 20 days, respectively at sampling calibrating in the 20th day, result compared with 0 day, and the stability result of investigation sample sees the following form 4.
The factorial experiments of table 4 felbinac compounds affect
| Time project | Proterties | Content (%) | Related substance (%) |
| 0 day | White crystalline powder | 99.97 | 0.02 |
| 60 DEG C 20 days | White crystalline powder | 99.97 | 0.02 |
| High light 20 days | White crystalline powder | 99.96 | 0.02 |
Sample 1 ~ sample 2 is carried out permanent stability investigation (25 DEG C ± 2 DEG C, RH 60% ± 10%), the results are shown in Table 5.
Table 5 felbinac compound long-term test results
Sample 1 ~ sample 2 is carried out accelerated stability investigation (40 DEG C ± 2 DEG C, RH 75% ± 5%), the results are shown in Table 6.
Table 6 felbinac accelerated test result
Above-mentioned test-results shows, felbinac compound stability prepared by the present invention is good, and foreign matter content is low, compares have obvious advantage with prior art.Felbinac compound prepared by other embodiments of the invention has also carried out identical test, obtains similar result.
Sample 3 ~ sample 5 is carried out accelerated stability investigation (40 DEG C ± 2 DEG C, RH 75% ± 5%), the results are shown in Table 7.
Table 7 felbinac gel accelerated test result
Above-mentioned test-results shows, effective constituent prepared by the present invention is that the felbinac gel stability of felbinac compound prepared by the present invention is good, and low the comparing with prior art of foreign matter content has obvious advantage
Sample 6 ~ sample 7 is carried out accelerated stability investigation (40 DEG C ± 2 DEG C, RH 75% ± 5%), the results are shown in Table 8.
Table 8 felbinac liniment accelerated test result
Above-mentioned test-results shows, effective constituent prepared by the present invention is the felbinac liniment good stability of felbinac compound prepared by the present invention, and low the comparing with prior art of foreign matter content has obvious advantage.
Claims (9)
1. felbinac compound, structural formula is such as formula shown in I:
Formula I
It is characterized in that: described felbinac compound is crystal, adopt X-ray powder diffraction to measure, in its collection of illustrative plates, characteristic peak ° is 5.8 °, 9.6 °, 11.7 °, 15.0 °, 16.3 °, 18.9 °, 19.4 °, 22.1 °, 25.2 °, 26.8 °, 28.5 °, 30.3 °, 33.2 °, 35.5 ° displays in 2 θ ± 0.2.
2. felbinac compound according to claim 1, is characterized in that: described felbinac melting point compound is 172 ~ 175 DEG C.
3. the preparation method of the felbinac compound described in claim 1 or 2, comprises the steps:
(1) felbinac raw material being dissolved in volume ratio is that in the methyl alcohol of 8:2 and the mixing solutions of acetone, the amount ratio of the mixing solutions of felbinac raw material and methyl alcohol and acetone is 1g:4ml;
(2) step (1) solution temperature is kept to be 24 ~ 33 DEG C, under the stirring velocity of 130 ~ 150 revs/min, with 80ml ~ 100ml/min speed, toward the solution in step (1), to add volume be the volume ratio of methyl alcohol and acetone mixing solutions 10 ~ 12 times in step (1) is water and the alcohol mixed solution of 9:1 while stirring, mixing solutions adds rear stopping and stirring, 2 ~ 4 DEG C are cooled to 0.4 ~ 0.6 DEG C/min speed, leave standstill growing the grain 8 hours, filter, obtain filter cake;
(3) will filter the water washing 2 times of the filter cake 2 times of weight obtained in step (2), 75 DEG C ~ 80 DEG C dryings 8 hours, namely obtain described felbinac compound.
4. felbinac pharmaceutical composition, is characterized in that: containing the felbinac compound described in claim 1 or 2.
5. felbinac pharmaceutical composition according to claim 4, is characterized in that: described felbinac pharmaceutical composition is gelifying agent, liniment, ointment, ointment or injection.
6. felbinac pharmaceutical composition according to claim 5, it is characterized in that: described gelifying agent, by 30g felbinac compound, 12g Acritamer 940,18g sodium hydroxide, 50g propylene glycol, 100g poly(oxyethylene glycol) 400,10g sodium tartrate, 500g water for injection, dehydrated alcohol adds to 1000g and prepares.
7. felbinac pharmaceutical composition according to claim 5, is characterized in that: described liniment, is added to 1000ml prepared by 30g felbinac compound, dehydrated alcohol.
8. the preparation method of felbinac pharmaceutical composition described in claim 6, is characterized in that comprising the following steps:
(1) sodium tartrate of recipe quantity is dissolved in the water for injection of half recipe quantity, then adds the Acritamer 940 of recipe quantity, fully swelling, stir, make Blank gel;
(2) be dissolved in the water for injection of surplus by the sodium hydroxide of recipe quantity, the poly(oxyethylene glycol) 400 of the propylene glycol and recipe quantity that then add recipe quantity stirs, then adds the felbinac of recipe quantity, stirring and dissolving;
(3) liquid in step (2) is slowly added in the Blank gel in step (1), then add dehydrated alcohol to full dose, constantly stir;
(4) intermediate after the assay was approved, flexible pipe loading, packs and get final product.
9. the preparation method of felbinac pharmaceutical composition described in claim 7, is characterized in that:
Be dissolved in the dehydrated alcohol of recipe quantity by the felbinac compound of recipe quantity, 0.22 μm of membrane filtration, intermediate is after the assay was approved, filling, packs and get final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410416465.5A CN104262138B (en) | 2014-08-22 | 2014-08-22 | A kind of felbinac compound and pharmaceutical composition thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410416465.5A CN104262138B (en) | 2014-08-22 | 2014-08-22 | A kind of felbinac compound and pharmaceutical composition thereof |
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| CN104262138A true CN104262138A (en) | 2015-01-07 |
| CN104262138B CN104262138B (en) | 2016-05-11 |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0338291A1 (en) * | 1988-04-21 | 1989-10-25 | American Cyanamid Company | Antiinflammatory Gel |
| GB2217596A (en) * | 1988-04-26 | 1989-11-01 | American Cyanamid Co | Anti-arthritic liposome composition |
| CN1073094A (en) * | 1991-10-01 | 1993-06-16 | 美国氰胺公司 | The pharmaceutical composition that contains felbinac (FELBINAC) |
| EP1342472A1 (en) * | 1999-10-01 | 2003-09-10 | Teikoku Seiyaku Co., Ltd. | Analgesic and anti-inflammatory patches for external use containing 4-biphenylylylacetic acid |
| JP2008069127A (en) * | 2006-09-15 | 2008-03-27 | Toko Yakuhin Kogyo Kk | Anti-inflammatory and analgesic cream preparation and method for producing the same |
| CN102503805A (en) * | 2011-10-26 | 2012-06-20 | 上海图帕医药科技有限公司 | Method for preparing 4-felbinac through rearrangement reaction |
| CN102525904A (en) * | 2012-02-08 | 2012-07-04 | 山东省医药工业研究所 | Stable felbinac gel and preparation method thereof |
-
2014
- 2014-08-22 CN CN201410416465.5A patent/CN104262138B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0338291A1 (en) * | 1988-04-21 | 1989-10-25 | American Cyanamid Company | Antiinflammatory Gel |
| GB2217596A (en) * | 1988-04-26 | 1989-11-01 | American Cyanamid Co | Anti-arthritic liposome composition |
| CN1073094A (en) * | 1991-10-01 | 1993-06-16 | 美国氰胺公司 | The pharmaceutical composition that contains felbinac (FELBINAC) |
| EP1342472A1 (en) * | 1999-10-01 | 2003-09-10 | Teikoku Seiyaku Co., Ltd. | Analgesic and anti-inflammatory patches for external use containing 4-biphenylylylacetic acid |
| JP2008069127A (en) * | 2006-09-15 | 2008-03-27 | Toko Yakuhin Kogyo Kk | Anti-inflammatory and analgesic cream preparation and method for producing the same |
| CN102503805A (en) * | 2011-10-26 | 2012-06-20 | 上海图帕医药科技有限公司 | Method for preparing 4-felbinac through rearrangement reaction |
| CN102525904A (en) * | 2012-02-08 | 2012-07-04 | 山东省医药工业研究所 | Stable felbinac gel and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 郭坚固等: "联苯乙酸搽剂的制备与质量研究", 《今日药学》, vol. 17, no. 1, 31 December 2008 (2008-12-31) * |
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