CN102908311B - Tolfenamic acid injection and preparation method and application thereof - Google Patents
Tolfenamic acid injection and preparation method and application thereof Download PDFInfo
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- CN102908311B CN102908311B CN201210436937.4A CN201210436937A CN102908311B CN 102908311 B CN102908311 B CN 102908311B CN 201210436937 A CN201210436937 A CN 201210436937A CN 102908311 B CN102908311 B CN 102908311B
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- tolfenamic acid
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- YEZNLOUZAIOMLT-UHFFFAOYSA-N tolfenamic acid Chemical compound CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O YEZNLOUZAIOMLT-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 229960002905 tolfenamic acid Drugs 0.000 title claims abstract description 59
- 238000002347 injection Methods 0.000 title claims abstract description 38
- 239000007924 injection Substances 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000008215 water for injection Substances 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 11
- 235000010234 sodium benzoate Nutrition 0.000 claims description 11
- 239000004299 sodium benzoate Substances 0.000 claims description 11
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 10
- 229960004194 lidocaine Drugs 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 8
- 239000012467 final product Substances 0.000 claims description 8
- 230000001954 sterilising effect Effects 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 5
- 239000003002 pH adjusting agent Substances 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 abstract description 11
- 230000036407 pain Effects 0.000 abstract description 11
- 239000006184 cosolvent Substances 0.000 abstract description 10
- 241000282472 Canis lupus familiaris Species 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 241000282326 Felis catus Species 0.000 abstract description 3
- 206010003246 arthritis Diseases 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 239000000730 antalgic agent Substances 0.000 abstract description 2
- 230000002917 arthritic effect Effects 0.000 abstract description 2
- 239000003755 preservative agent Substances 0.000 abstract description 2
- 229940121657 clinical drug Drugs 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 230000002421 anti-septic effect Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 238000012216 screening Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000036592 analgesia Effects 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 229960004365 benzoic acid Drugs 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 208000004550 Postoperative Pain Diseases 0.000 description 2
- 238000009360 aquaculture Methods 0.000 description 2
- 244000144974 aquaculture Species 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- DJGAAPFSPWAYTJ-UHFFFAOYSA-M metamizole sodium Chemical compound [Na+].O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 DJGAAPFSPWAYTJ-UHFFFAOYSA-M 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 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
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 2
- 238000009806 oophorectomy Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229960003885 sodium benzoate Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- -1 3-chloro-2-methyl phenyl Chemical group 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007159 enucleation Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000008533 pain sensitivity Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013190 sterility testing Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a tolfenamic acid injection and a preparation method and application thereof. The tolfenamic acid injection disclosed by the invention comprises a main drug, a cosolvent, a pH regulator, a preservative agent and a local analgetic agent. The tolfenamic acid injection disclosed by the invention is safe and convenient to use and controllable in quality; the preparation process of the tolfenamic acid injection is stable, suitable for industrial production and low in cost; and the tolfenamic acid injection enriches veterinary clinical drugs and has obvious effect if being used for treating arthritis, arthritic pain and surgical pain of dogs, cats and the like.
Description
Technical field
The present invention relates to veterinary formulations field, be specifically related to a kind of tolfenamic acid injection and preparation method thereof.
Background technology
In recent years along with the raising of living standards of the people, also increasing to the demand of the raising of house pet, the wide market space accelerates aquaculture and the fast development of house pet industry especially.While aquaculture and the fast development of house pet industry, to inflammation, pain that the treatment of house pet disease brings, also more and more receive the concern of house pet master, along with the status of house pet in the heart of people strengthens gradually, the health status of house pet causes the attention of people more.How to reduce pet treat or ill time produce pain, market there is a lot of antiinflammatory, analgesic drug, to reduce the sick and wounded injury brought of house pet.Calculate according to data, domestic have house pet 100,000,000 (head) at least, and house pet quantity is by growth by 5 times in the five-year, the market potential of pets economy at least can reach 15,000,000,000 yuans, and the antipyretic-antalgic anti-inflammatory agent thing that wherein curative effect is good must occupy a tiny space.
Tolfenamic acid is the anthranilic acid derivative (Tolfenamic acid) developed by GEA company of Denmark, is a kind of widely used nonsteroidal anti-inflammatory drug.Its chemical name is: 2-[(3-chloro-2-methyl phenyl) is amino] benzoic acid, molecular formula: C
14h
12clNO
2, molecular weight: 261.70, chemical structural formula:
Tolfenamic acid belongs to non_steroidal anti_inflammatory drug, has antiinflammatory, analgesia and refrigeration function.Tolfenamic acid has stronger selectivity to COX-2, and the mechanism of action mainly plays anti-inflammatory analgesic action by suppressing Cycloxygenase (COX) to reduce arachidonic acid (AA) to inflammatory mediator prostaglandin (PGs) conversion.Tolfenamic acid is since the eastern Pedicellus et Pericarpium Trapae pharmaceutical industries of Japan in May nineteen eighty-three is using the trade name of Clotam as treatment arthritis and first listing of migraine people medication, and the manufacturer that market is main abroad is at present France and Canadian Vetoquinol company.Tolfenamic acid listed a company for veterinary clinic in 1994 by Vetoquinol, was mainly used in the antiinflammatory of dog, cat etc., antipyretic, analgesia therapy.Research data shows, tolfenamic acid has higher safety, can safety applications in veterinary clinic, have a wide range of applications.Domestic at present not yet have the clinical practice of tolfenamic acid on animal,
Tolfenamic acid is poorly soluble, and be prepared into liquid preparation instability, the present invention proposes a solution, solve the problem of injection instability, we have developed the injection of tolfenamic acid for this reason, for reducing the sensitivity of dog to pain, reduce inflammation reaction, alleviates postoperative pain.
Summary of the invention
The present invention provides a kind of tolfenamic acid injection being used for the treatment of the arthritis such as Canis familiaris L., cat, Arthritic pain and operation pain first.
One object of the present invention is the preparation method providing above-mentioned tolfenamic acid injection.
Another object of the present invention is the purposes providing above-mentioned tolfenamic acid injection.
Above-mentioned purpose of the present invention is achieved by the following technical programs:
The invention provides a kind of tolfenamic acid injection, consisting of of this injection: tolfenamic acid, cosolvent, pH adjusting agent, antiseptic, local analgesia agent and solvent for injection.
The present invention, the composition of each component by weight:
PH value is 9.5.
Preferably, formula of the present invention is composed as follows:
PH value is 9.5.
Preferred further, formula of the present invention is composed as follows:
PH value is 9.5.
Wherein, described cosolvent is one or more in propylene glycol, glycerol, dimethyl formamide, N-Methyl pyrrolidone, ethanol, preferred N-Methyl pyrrolidone.Described pH adjusting agent is NaOH, Na
2cO
3, NaHCO
3, triethanolamine, one or more in ethanolamine, preferred NaOH.Described antiseptic is one in benzyl alcohol, methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, benzoic acid, sodium benzoate, preferred sodium benzoate.Described local analgesia agent is one in benzyl alcohol, chlorobutanol, procaine hydrochloride or lignocaine, preferred lignocaine.
Formula composition of the present invention is through screening acquisition, and screening process is as follows:
Table 1, the dissolubility of tolfenamic acid in different cosolvent:
Therefore, preferred co-solvents is one or more in propylene glycol, glycerol, dimethyl formamide, N-Methyl pyrrolidone, ethanol.According to the dissolving situation of tolfenamic acid at cosolvent, the dosage of cosolvent there is preferably 20-40ml.
Described antiseptic be benzyl alcohol, methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, benzoic acid, sodium benzoate one of them.
Table 2, tolfenamic acid injection of the present invention adopts the different preservatives accelerated test Sterility testing result of 3 months:
Described aqueous slkali is selected from NaOH, Na of 1%-20%
2cO
3or NaHCO
3.
Table 3, described in tolfenamic acid injection of the present invention, aqueous slkali screening table is as follows:
According to the result of trial test adjuvant screening, find that cosolvent, antiseptic, pH value three factors all have a certain impact to tolfenamic acid injection stability.Therefore form three variable factors with cosolvent, antiseptic, pH value, each factor selectes three levels, in table 4, by statistical analysis (L
9) 3
3orthogonal trial is tested.
Table 4 Three factors-levels designs
Processing method adds each adjuvant according to each recipe quantity of the Three factors listed by table 4, preparation tolfenamic acid injection 1. ~ 9. injection.Get sample segment and be placed in 4 ° of C preservations, observed in 1 month in medicinal liquid and separate out with or without medicine; Separately get sample segment to preserve under 60 ° of C hot conditionss, respectively at sampling in the 5th, 10 day, investigate solution colour change, and measure tolfenamic acid content.
Performance assessment criteria and standards of grading place 10d butt that acid content fragrant with 60 ° of C high temperature, the change of medicinal liquid color and low tempertaure storage were performance assessment criteria with or without Precipitation after 1 month, concrete standards of grading are that tolfenamic acid content often declines and 0.5 to add 1 point (>=0.25 enters, and < 0.25 gives up); The most shallow person of color is 0 point, and often a dark color solution adds 5 points; Be 0 point without Precipitation, have precipitation to add 5 points.
Table 5, orthogonal test observed result
From showing 10-5, after 60 ° of C high temperature place 10d, No. 6 injection colors the most shallow (color is equivalent to yellow No. 8 standard color solutions), obtain 0 point, remaining injection liquid color is slightly dark, all obtains 5 points.1 ~ No. 9 injection, 4 ° of C preserve one monthly without Precipitation phenomenon.In 9 kinds of prescription compages, score the lowest (best prescription combination) is No. 6 prescriptions, i.e. A
2b
3c
1.
Screened by prescription orthogonal test and optimize, the best adjuvant prescription determining tolfenamic acid injection is cosolvent is 30, and antiseptic is 2, and pH value is 9.5.
Therefore, the most preferred formula of the present invention is as follows:
Tolfenamic acid 4g
N-Methyl pyrrolidone 30g
Sodium benzoate 2g
Lignocaine 0.1g
Water for injection is added to 100ml
PH adjusting agent is appropriate, regulates pH value to be 9.5.
The preparation method of tolfenamic acid injection of the present invention, comprises the steps:
(1) by formula ratio, tolfenamic acid is added in 60-80 DEG C of cosolvent, tolfenamic acid is dissolved, cooling, for subsequent use;
(2) dissolve antiseptic and local analgesic with appropriate water for injection, mix with the reserve liquid in step (1), add water for injection to full dose, stir 10 minutes, add the pH to 8.5-10 that pH adjusting agent regulates solution;
(3) filter, embedding, sterilizing 100 DEG C, 30min, to obtain final product.
The color of tolfenamic acid injection of the present invention is faint yellow, may be used for reducing dog to the sensitivity of pain, and reduce inflammation reaction, alleviates postoperative pain.Its route of administration can be, but not limited to subcutaneous injection.
Three batch samples of table 6, embodiment 1, checked for impurities content:
| Sample | Impurity content % |
| 1st batch | 0.52 |
| 2nd batch | 0.64 |
| 3rd batch | 0.38 |
From test data, three batches of injection impurity contents of embodiment 1 are few.
Another experimental group room temperature places 90 days, then checked for impurities content three batches, and result is as following table:
| Sample | Impurity content % |
| 1st batch | 0.67 |
| 2nd batch | 0.68 |
| 3rd batch | 0.62 |
From test data, three batches of injection impurity contents of embodiment 1 are less than 1%, show that product stability is good.Formula of the present invention is through screening acquisition, has following beneficial effect:
(1) tolfenamic acid injection formulation of the present invention is stablized, quality controllable, can suitability for industrialized production;
(2) tolfenamic acid injection Clinical practice of the present invention is convenient, for veterinary clinic provides quality product, has filled up domestic blank.
(3) compared to the prior art, formulation stability of the present invention is good, and standing time is long, and clarity is high, and bioavailability is high.
Detailed description of the invention
Explain the present invention further below in conjunction with embodiment, but embodiment does not limit in any form to the present invention.
Embodiment 1
The tolfenamic acid getting 40g adds in 300gN-methyl pyrrolidone, and 60-80 DEG C of heating makes tolfenamic acid dissolve, cooling, for subsequent use; Separately get 200ml water for injection and add 20g sodium benzoate and 1g lignocaine, dissolve, mix with reserve liquid; Add water for injection to full dose 1000ml, stir 10 minutes, add the pH to 9.5 that NaOH regulates solution; Filter, embedding, sterilizing 100 DEG C, 30min, to obtain final product.
Embodiment 2
The tolfenamic acid getting 20g adds in 100gN-methyl pyrrolidone, and 60-80 DEG C of heating makes tolfenamic acid dissolve, cooling, for subsequent use; Separately get 200ml water for injection and add 10g sodium benzoate and 1.5g lignocaine, dissolve, mix with reserve liquid; Add water for injection to full dose 1000ml, stir 10 minutes, add the pH to 8.5 that NaOH regulates solution; Filter, embedding, sterilizing 100 DEG C, 30min, to obtain final product.
Embodiment 3
The tolfenamic acid getting 100g adds in 200gN-methyl pyrrolidone, and 60-80 DEG C of heating makes tolfenamic acid dissolve, cooling, for subsequent use; Separately get 200ml water for injection and add 30g sodium benzoate and 1g lignocaine, dissolve, mix with reserve liquid; Add water for injection to full dose 1000ml, stir 10 minutes, add the pH to 10 that NaOH regulates solution; Filter, embedding, sterilizing 100 DEG C, 30min, to obtain final product.
Embodiment 4
The tolfenamic acid getting 40g adds in 500g propylene glycol, and 60-80 DEG C of heating makes tolfenamic acid dissolve, cooling, for subsequent use; Separately get 200ml water for injection and add 10g sodium benzoate and 15g lignocaine, dissolve, mix with reserve liquid; Add water for injection to full dose 1000ml, stir 10 minutes, add the pH to 8.5-10 that NaOH regulates solution; Filter, embedding, sterilizing 100 DEG C, 30min, to obtain final product.
Embodiment 5
The tolfenamic acid getting 50g adds in 200g propylene glycol, and 60-80 DEG C of heating makes tolfenamic acid dissolve, cooling, for subsequent use; Separately get 300ml water for injection and add 10g sodium benzoate and 1g lignocaine, dissolve, mix with reserve liquid; Add water for injection to full dose 1000ml, stir 10 minutes, add the pH to 8.5-10 that NaOH regulates solution; Filter, embedding, sterilizing 100 DEG C, 30min, to obtain final product.
Clinical trial
The clinical health dog of plant 18, selects uterus oophorectomy (OHE) as pain model.Before anesthesia, press 4mg/kg injected sc tolfenamic acid injection, then carry out ovary and uterus enucleation, adopt Melbourne Pain Scale (MPS) method to mark to its pain.
After this result of the test statistical analysis, tolfenamic acid administration group and analgin injection drug control group with process not administration matched group gained pain score through statistical analysis difference extremely significantly (P<0.01), until postoperative 24h administration group with process not administration matched group and still there is significant difference (P<0.01), result shows, tolfenamic acid injection has obvious analgesic effect, and effect is better than analgin injection control drug.
Claims (3)
1. a tolfenamic acid injection, is characterized in that, the composition of each component is by weight:
Water for injection is added to 100ml
Adjust ph is 9.5.
2. the preparation method of the tolfenamic acid injection of claim 1, it is characterized in that, step is as follows:
(1) by formula ratio, tolfenamic acid is added in the N-Methyl pyrrolidone of 60-80 DEG C, tolfenamic acid is dissolved, cooling, for subsequent use;
(2) dissolve sodium benzoate and lignocaine with appropriate water for injection, mix with the reserve liquid in step (1), add water for injection to full dose, stir 10 minutes, add the pH to 9.5 that pH adjusting agent regulates solution;
(3) filter, embedding, sterilizing 100 DEG C, 30min, to obtain final product.
3. a preparation method for tolfenamic acid injection, is characterized in that, step is as follows:
The tolfenamic acid getting 40g adds in 300gN-methyl pyrrolidone, and 60-80 DEG C of heating makes tolfenamic acid dissolve, cooling, for subsequent use; Separately get 200ml water for injection and add 20g sodium benzoate and 1g lignocaine, dissolve, mix with reserve liquid; Add water for injection to full dose 1000ml, stir 10 minutes, add the pH to 9.5 that NaOH regulates solution; Filter, embedding, sterilizing 100 DEG C, 30min, to obtain final product.
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| 托芬那酸的药理毒理研究;付海宁等;《中国兽药杂志》;20101231;第44卷(第8期);52-56 * |
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