CN101485650B - Diclofenac sodium and lidocaine hydrochloride injection and preparation method thereof - Google Patents
Diclofenac sodium and lidocaine hydrochloride injection and preparation method thereof Download PDFInfo
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- CN101485650B CN101485650B CN 200910014260 CN200910014260A CN101485650B CN 101485650 B CN101485650 B CN 101485650B CN 200910014260 CN200910014260 CN 200910014260 CN 200910014260 A CN200910014260 A CN 200910014260A CN 101485650 B CN101485650 B CN 101485650B
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- 229960001193 diclofenac sodium Drugs 0.000 title claims abstract description 70
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 title claims abstract description 70
- 229960004393 lidocaine hydrochloride Drugs 0.000 title claims abstract description 58
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 238000002347 injection Methods 0.000 title claims abstract description 55
- 239000007924 injection Substances 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 239000000243 solution Substances 0.000 claims description 92
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 48
- 238000003756 stirring Methods 0.000 claims description 26
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 22
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 19
- 239000002202 Polyethylene glycol Substances 0.000 claims description 16
- 229920001223 polyethylene glycol Polymers 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 14
- 235000010265 sodium sulphite Nutrition 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 239000003643 water by type Substances 0.000 claims description 10
- 230000001954 sterilising effect Effects 0.000 claims description 9
- 239000008215 water for injection Substances 0.000 claims description 8
- 230000001105 regulatory effect Effects 0.000 claims description 7
- 239000011734 sodium Substances 0.000 claims description 7
- 238000004659 sterilization and disinfection Methods 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 3
- 238000012856 packing Methods 0.000 claims description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 230000007547 defect Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000047 product Substances 0.000 description 18
- 238000012360 testing method Methods 0.000 description 8
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- 239000007864 aqueous solution Substances 0.000 description 3
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- 230000017074 necrotic cell death Effects 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229960003511 macrogol Drugs 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
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- 206010030113 Oedema Diseases 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
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- 238000000151 deposition Methods 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
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- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
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- 239000003112 inhibitor Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
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- 206010033675 panniculitis Diseases 0.000 description 1
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- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
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- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
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- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to the technical field of medicines, in particular to a diclofenac sodium lidocaine hydrochloride injection and a method for preparing the same. The invention aims to overcome defects in the prior art and provides the diclofenac sodium lidocaine hydrochloride injection with stable quality. Moreover, the invention also provides a method for preparing the diclofenac sodium lidocaine hydrochloride injection, which can avoid the technical difficult problem that the active ingredient, namely diclofenac sodium is separated out during the preparation of the injection.
Description
Technical field
The invention belongs to medical technical field, particularly, the present invention relates generally to a kind of diclofenac sodium lidocaine hydrochloride injection, and the present invention provides its preparation method simultaneously.
Background technology
Diclofenac sodium, chemical name is 2-[(2, the 6-Dichlorobenzene base) amino] phenylacetic acid list sodium salt, this product is applied to various rheumatism, rheumatoid arthritis, neuritis, lupus erythematosus, ankylosing spondylitis, the heating that the pain that causes behind the cancer operation and a variety of causes cause etc., it can reduce the synthetic of prostaglandin, prostacyclin and thromboxane product as the potent inhibitor of Cycloxygenase, thereby reaches the purpose of easing pain and diminishing inflammation.When the diclofenac sodium injection used in injection, the sense of patient's feels pain was strong.Lidocaine hydrochloride is a kind of preparation for callouse, after being prepared into the diclofenac sodium lidocaine hydrochloride injection, can reduce patient's local injection pain.
The dissolubility of diclofenac sodium in water is less, and common process prepares in the diclofenac sodium lidocaine hydrochloride injection process, occurs the diclofenac sodium problem that crystallization is separated out in aqueous solution easily.
Among the CN1711996A, once mentioned and utilize beta-schardinger dextrin-to improve diclofenac sodium dissolubility in aqueous solution, but, even utilize above-mentioned technology, when diclofenac sodium concentration in aqueous solution reaches 30mg/ml and when above, again lidocaine hydrochloride is joined in the diclofenac sodium water solution, the problem that the diclofenac sodium crystallization is separated out also takes place easily.
Simultaneously, product colour flavescence, the too much problem of product content decline often take place, unstable product quality in the diclofenac sodium lidocaine hydrochloride injection of prior art for preparing when sterilizing with routine techniques.
Summary of the invention
The present invention seeks to overcome the prior art deficiency, a kind of stay-in-grade diclofenac sodium lidocaine hydrochloride injection is provided.
The invention provides a kind of preparation method of diclofenac sodium lidocaine hydrochloride injection, the technical barrier that this method can avoid the active ingredient diclofenac sodium to separate out in the preparation of product process.
Diclofenac sodium lidocaine hydrochloride injection of the present invention contains diclofenac sodium, lidocaine hydrochloride, disodiumedetate, reaches in propylene glycol, Polyethylene Glycol, the sodium sulfite one or more.
Diclofenac sodium lidocaine hydrochloride injection of the present invention, optimizing prescriptions is: containing diclofenac na concn content is 30～50mg/ml, lidocaine hydrochloride content is 10～15mg/ml, disodiumedetate content is 1～3mg/ml, content of propylene glycol is 10%～20% (V/V), and polyethyleneglycol content is 15%～30% (V/V).
Diclofenac sodium lidocaine hydrochloride injection of the present invention, best prescription is: containing the diclofenac sodium content is 37.5mg/ml, lidocaine hydrochloride content is 11.5mg/ml, disodiumedetate content is 1.25mg/ml, content of propylene glycol is 15% (V/V), and polyethyleneglycol content is 21%.
The invention described above diclofenac sodium lidocaine hydrochloride injection, the preferred PEG400 of Polyethylene Glycol wherein.
The invention described above diclofenac sodium lidocaine hydrochloride injection, disodiumedetate wherein can replace with calcio-disodium edetate.
The invention provides a kind of preparation method of diclofenac sodium lidocaine hydrochloride injection, wherein comprise following preparation process:
1. get an amount of sodium sulfite and disodiumedetate, join in 35～45 ℃ of waters for injection, stir and make dissolving, be prepared into the mixed solution that disodiumedetate content is 4～12mg/ml, get solution A;
2. proportioning by volume, propylene glycol: Polyethylene Glycol: solution A=(40～80): (60～120): 100, get propylene glycol and Polyethylene Glycol, join in the above-mentioned solution A, mix, get solution B;
3. get 2/3 of above-mentioned solution B volume, add diclofenac sodium, stir and make dissolving, get solution C;
4. get 1/3 of above-mentioned solution B volume, add lidocaine hydrochloride, stir and make dissolving, get solution D;
5. getting above-mentioned solution C, solution D, mix, replenish water for injection to 4 times of the solution A volume, is the Na of 100mg/ml with concentration
2CO
3Solution is regulated pH value to 8.0～8.5, gets solution E;
6. get solution E, conventional method is filtered, fill, and sterilization, packing namely gets diclofenac sodium lidocaine hydrochloride injection of the present invention.
In above-mentioned preparation method step, step 1. in preferred 40 ℃ of the temperature of water for injection.
In above-mentioned preparation method step, step 5. in, Na
2CO
3Solution is regulated pH value preferably to 8.2.
In order to illustrate that diclofenac sodium lidocaine hydrochloride injection of the present invention has good stability and safety, according to embodiment 1 preparation diclofenac sodium lidocaine hydrochloride injection of the present invention, sterilising conditions is selected 115 ℃ of pressure sterilizing 30min, gets product one of the present invention.Place it in the room temperature environment, during respectively at firm placement, place sample thief check in 3,6,12,24 months, observe its outward appearance and measure diclofenac sodium and lidocaine hydrochloride content and its related substances, result of the test is as follows:
Table 1 diclofenac sodium lidocaine hydrochloride injection room temperature is investigated the stability test result
As can be seen from Table 1, diclofenac sodium lidocaine hydrochloride injection of the present invention is after room temperature is deposited 24 months, and product content and related substance do not change than basic with depositing preliminary phase, illustrate that quality stability of the present invention is good.
Get 6 of the healthy new zealand rabbits of body weight 2.1-2.5kg, benefit people pharmaceutical factory provides by Shandong, and the male and female dual-purpose is divided into two groups, i.e. medicine group and matched group at random.Rabbit is placed in the holder, medicine group rabbit left side auricular vein instillation product one 10ml/kg of the present invention, the matched group rabbit left side auricular vein 0.9% normal saline 10ml/kg that instils, drip velocity is 1ml/min, every day 1 time, for three days on end.During the instillation and after instiling, note observing the instillation position and have or not stimulations such as redness, hyperemia, hemorrhage and necrosis., with sacrifice of animal, cut the left side rabbit ear and draw materials apart from inserting needle position proximal part 1cm place after 24 hours in the last administration, carry out histopathologic examination.
Result of the test:
Perusal: irritant reaction such as tangible redness, hyperemia, necrosis do not appear in instillation product of the present invention one rabbit ear position, with the rabbit ear no significant difference of the 0.9% sodium chloride injection group that instils.
Pathological examination: 9% sodium chloride injection matched group: sending specimen is rabbit ear tissue.The skin histology structure is normal, and epidermis does not have and thickens, and subcutaneous tissue is not seen morphological changes such as hyperemia, edema.Auricular vein is not seen expansion, and vascular endothelial cell do not see yet and increase and change such as arrangement disorder, and blood vessel wall does not have and thickens changes such as no mural thrombus and inflammatory cell infiltration in the official jargon.
Product one administration group of the present invention: the same matched group of microscopy rabbit ear tectology, tube wall is not seen mural thrombus, significances such as inorganization degeneration or necrosis stimulate, and do not have obvious pathomorphology and change.
Conclusion: intravenous drip product one no obvious vascular stimulation effect of the present invention.
Get not through product of the present invention one solution of sterilization, be semi-finished product; Remove the disodiumedetate in the embodiment 1 product prescription, other steps are constant, preparation test specimen one; Sterilising conditions is changed to 100 ℃ of pressure sterilizing 30min, and other conditions are same as preparation test products one, preparation test specimen two.Observe the said goods outward appearance, measure diclofenac sodium content and related substance, the result is as follows:
Table 2 diclofenac sodium lidocaine hydrochloride injection engineer testing result
Illustrate in the diclofenac sodium lidocaine hydrochloride injection of the present invention, add disodiumedetate and can effectively improve the quality of products.
Another contribution of the present invention has been to provide a kind of preparation method of diclofenac sodium lidocaine hydrochloride injection, and this method has solved in this preparation of product process, and diclofenac sodium is separated out the prior art deficiency of crystallization.
According to the embodiment of the invention 1～7 preparation diclofenac sodium lidocaine hydrochloride injection of the present invention, find all that in the preparation of product process two sodium chlorate separate out crystalline polamer and take place.
According to prior art for preparing diclofenac sodium lidocaine hydrochloride injection, preparation method is as follows:
Test one:
1. get weight portion sodium sulfite 3g, disodiumedetate 1g joins in 35 ℃ of waters for injection of 250ml, stirs and makes dissolving, gets solution A;
2. get an amount of propylene glycol 150ml and Polyethylene Glycol 210ml, join in the above-mentioned solution A, mix, get solution B;
3. get above-mentioned solution B, add diclofenac sodium 30g, stir and make dissolving, get solution C;
4. get above-mentioned solution C, add lidocaine hydrochloride 10g, stirred 5 minutes, have crystal to separate out, filtration must be separated out crystal, detects to be diclofenac sodium.
Test two:
Get diclofenac sodium 30g, join among the water for injection 1000ml, stir make dissolve diclofenac sodium solution b.Add lidocaine hydrochloride 10g again in solution b, stirred 5 minutes, have crystal to separate out, filter, detecting and separating out crystal is diclofenac sodium.
Specific embodiment
In order to understand better and to implement the present invention, the specific embodiment of the invention is explained, but the present invention never only limits to this
Embodiment 1
1. get weight portion sodium sulfite 3g, disodiumedetate 1.25g joins in 40 ℃ of waters for injection of 250ml, stirs and makes dissolving, gets solution A;
2. get propylene glycol 150ml and Polyethylene Glycol 210ml, join in the above-mentioned solution A, mix, get solution B;
3. get 2/3 of above-mentioned solution B volume, add diclofenac sodium 37.5g, stir and make dissolving, get solution C;
4. get 1/3 of above-mentioned solution B volume, add lidocaine hydrochloride 11.5g, stir and make dissolving, get solution D;
5. getting above-mentioned solution C, solution D, mix, replenish water for injection to 1000ml, is the Na of 100mg/ml with concentration
2CO
3Solution is regulated pH value to 8.2, gets solution E;
6. get solution E, conventional method is filtered, fill, and sterilization, packing namely gets diclofenac sodium lidocaine hydrochloride injection of the present invention.
Embodiment 2
1. get weight portion sodium sulfite 3g, disodiumedetate 1g joins in 35 ℃ of waters for injection of 250ml, stirs and makes dissolving, gets solution A;
2. get propylene glycol 100ml and Polyethylene Glycol 150ml, join in the above-mentioned solution A, mix, get solution B;
3. get 2/3 of above-mentioned solution B volume, add diclofenac sodium 30g, stir and make dissolving, get solution C;
4. get 1/3 of above-mentioned solution B volume, add lidocaine hydrochloride 10g, stir and make dissolving, get solution D;
Other steps namely get diclofenac sodium lidocaine hydrochloride injection of the present invention with embodiment 1.
Embodiment 3
1. get weight portion sodium sulfite 3g, disodiumedetate 3g joins in 45 ℃ of waters for injection of 250ml, stirs and makes dissolving, gets solution A;
2. get propylene glycol 200ml and Liquid Macrogol ml, join in the above-mentioned solution A, mix, get solution B;
3. get 2/3 of above-mentioned solution B volume, add diclofenac sodium 50g, stir and make dissolving, get solution C;
4. get 1/3 of above-mentioned solution B volume, add lidocaine hydrochloride 15g, stir and make dissolving, get solution D;
5. getting above-mentioned solution C, solution D, mix, replenish water for injection to 1000ml, is the Na of 100mg/ml with concentration
2CO
3Solution is regulated pH value to 8.5, gets solution E;
Other steps namely get diclofenac sodium lidocaine hydrochloride injection of the present invention with embodiment 1.
Embodiment 4
1. get weight portion sodium sulfite 3g, disodiumedetate 3g joins in 45 ℃ of waters for injection of 250ml, stirs and makes dissolving, gets solution A;
2. get propylene glycol 200ml and Liquid Macrogol ml, join in the above-mentioned solution A, mix, get solution B;
3. get 2/3 of above-mentioned solution B volume, add diclofenac sodium 50g, stir and make dissolving, get solution C;
4. get 1/3 of above-mentioned solution B volume, add lidocaine hydrochloride 15g, stir and make dissolving, get solution D;
5. getting above-mentioned solution C, solution D, mix, replenish water for injection to 1000ml, is the Na of 100mg/ml with concentration
2CO
3Solution is regulated pH value to 8.0, gets solution E;
Other steps namely get diclofenac sodium lidocaine hydrochloride injection of the present invention with embodiment 1.
Embodiment 5
1. get weight portion sodium sulfite 4g, disodiumedetate 2g joins in 40 ℃ of waters for injection of 250ml, stirs and makes dissolving, gets solution A;
2. get propylene glycol 180ml and Polyethylene Glycol 250ml, join in the above-mentioned solution A, mix, get solution B;
3. get 2/3 of above-mentioned solution B volume, add diclofenac sodium 35g, stir and make dissolving, get solution C;
4. get 1/3 of above-mentioned solution B volume, add lidocaine hydrochloride 13g, stir and make dissolving, get solution D;
Other steps namely get diclofenac sodium lidocaine hydrochloride injection of the present invention with embodiment 1.
Embodiment 6
1. get weight portion sodium sulfite 2g, disodiumedetate 2.5g joins in 40 ℃ of waters for injection of 250ml, stirs and makes dissolving, gets solution A;
2. get propylene glycol 130ml and Polyethylene Glycol 210ml, join in the above-mentioned solution A, mix, get solution B;
Other steps namely get diclofenac sodium lidocaine hydrochloride injection of the present invention with embodiment 1.
Embodiment 7
1. get weight portion sodium sulfite 3g, calcio-disodium edetate 1.25g joins in 40 ℃ of waters for injection of 250ml, stirs and makes dissolving, gets solution A;
Other steps namely get diclofenac sodium lidocaine hydrochloride injection of the present invention with embodiment 1.
Claims (5)
1. the preparation method of a diclofenac sodium lidocaine hydrochloride injection is characterized in that comprising following preparation process:
1. get an amount of sodium sulfite and disodiumedetate, join in 35～45 ℃ of waters for injection, stir and make dissolving, be prepared into the mixed solution that disodiumedetate content is 4～12mg/ml, get solution A;
2. proportioning by volume, propylene glycol: Polyethylene Glycol: solution A=(40～80): (60～120): 100, get propylene glycol and Polyethylene Glycol, join in the above-mentioned solution A, mix, get solution B;
3. get 2/3 of above-mentioned solution B volume, add diclofenac sodium, stir and make dissolving, get solution C;
4. get 1/3 of above-mentioned solution B volume, add lidocaine hydrochloride, stir and make dissolving, get solution D;
5. getting above-mentioned solution C, solution D, mix, replenish water for injection to 4 times of the solution A volume, is the Na of 100mg/ml with concentration
2CO
3Solution is regulated pH value to 8.0～8.5, gets solution E;
6. get solution E, the conventional method fill, sterilization, packing namely gets the diclofenac sodium lidocaine hydrochloride injection;
Described diclofenac sodium lidocaine hydrochloride injection, the diclofenac sodium content is 30～50mg/ml, lidocaine hydrochloride content is 10～15mg/ml, disodiumedetate content is 1～3mg/ml, content of propylene glycol is 10%～20% (V/V), and polyethyleneglycol content is 15%～30% (V/V).
2. the preparation method of diclofenac sodium lidocaine hydrochloride injection as claimed in claim 1, it is characterized in that the diclofenac sodium content is 37.5mg/ml, lidocaine hydrochloride content is 11.5mg/ml, disodiumedetate content is 1.25mg/ml, content of propylene glycol is 15% (V/V), and polyethyleneglycol content is 21%.
3. the preparation method of diclofenac sodium lidocaine hydrochloride injection as claimed in claim 1 is characterized in that Polyethylene Glycol is PEG400.
4. the preparation method of diclofenac sodium lidocaine hydrochloride injection as claimed in claim 1 is characterized in that the temperature of water for injection was 40 ℃ during step 1..
5. the preparation method of diclofenac sodium lidocaine hydrochloride injection as claimed in claim 1 is characterized in that step 5., is the Na of 100mg/ml with concentration
2CO
3Solution is regulated pH value to 8.2.
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| CN102078290B (en) * | 2009-11-26 | 2014-01-15 | 华北制药集团制剂有限公司 | Method for preparing carbonate lidocaine injection |
| CN104274436B (en) * | 2013-07-03 | 2017-05-10 | 成都力思特制药股份有限公司 | Diclofenac sodium lidocaine hydrochloride compound drug injection liquid and preparation method thereof |
| CN104288096A (en) * | 2014-06-24 | 2015-01-21 | 郑州百瑞动物药业有限公司 | Injection for treating pyrexia and hoof disease of dairy cows, and its preparation method |
| CN104434893A (en) * | 2014-11-14 | 2015-03-25 | 海南通用康力制药有限公司 | Diclofenac sodium lidocaine hydrochloride freeze-dried powder injection for injection and preparation method of freeze-dried powder injection |
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