CN102138891A - Ketorolac tromethamine injection - Google Patents
Ketorolac tromethamine injection Download PDFInfo
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- CN102138891A CN102138891A CN2010101153684A CN201010115368A CN102138891A CN 102138891 A CN102138891 A CN 102138891A CN 2010101153684 A CN2010101153684 A CN 2010101153684A CN 201010115368 A CN201010115368 A CN 201010115368A CN 102138891 A CN102138891 A CN 102138891A
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Abstract
The invention discloses a ketorolac tromethamine injection characterized by being prepared from the following components in percentage by weight: 0.1-15 percent of ketorolac tromethamine, 0.01-10 percent of buffering agent and 0.001-5 percent of pH value regulator. In the invention, because a traditional menstruum, such as ethanol is replaced by a phosphate buffer solution, the ketorolac tromethamine injection with good stability, less irritation, safety and more convenience is obtained so as to improve the medicament compliance of patients and the clinical medication convenience.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, specifically, the present invention relates to a kind of NSAID (non-steroidal anti-inflammatory drug) Ketoralac ammonia butanetriol injection system.
Background technology
Ketorolac tromethamine (Ketorolac Tromethamine) belongs to nonsteroidal anti-inflammatory drug.In clinical being mainly used in, severe pain such as postoperative, fracture, sprain, the pain relieving of toothache and carcinomas pain etc.It is a kind of cox-2 inhibitors, the generation of alternative arachidonic Cycloxygenase of blocking-up and prostaglandin, thereby excellent analgesia, antiinflammatory and the usefulness of bringing down a fever of performance.It does not directly act on opiate receptor, thereby does not have addiction trend, does not more have the untoward reaction of nervus centralis or opioid analgesics.
Ketorolac tromethamine does not have the addiction and the taboo symptom of morphine, it is behind intravenous injection 30mg, on average the highest blood level can occur in 2.9 ± 1.8 minutes, intramuscular injection absorbs rapidly and is complete, the highest blood level can occur in 30～60 minutes behind the single dose intramuscular injection 60mg, because ketorolac tromethamine has the multicell Distribution Effect, protein binding rate is about 99%, the distribution volume of CONCENTRATION STATE is 0.11L/kg in the average stabilised blood, the distribution volume of draining phase is 0.17～0.25L/kg, on average drains the half-life to be about 5.3 hours.
Ketorolac tromethamine can be dissociated into the anion kenel under physiology pH value environment, and the decline situation of its blood level can be described by excretory two Room property in central compartment or three Room sexual norms.Mainly via liver metabolism, being combined into the non-activity thing with glycuronic acid is main metabolic pathway.
The pH value of this medicine must just can be guaranteed effectiveness, safety, stability at the pH value 6.9～7.9 of certain limit, so need to adjust with soda acid or buffer agent.The tradition Ketoralac ammonia butanetriol injection contains the injection of ethanol or other solvent, yet the injection that contains organic solvent such as ethanol has certain toxicity, and is easy to generate zest during injection, reduces patient dependence.In addition, clinically, the ketorolac tromethamine injection share with injection such as morphines often, and ethanol has certain influence to the absorption metabolism of morphine, increase the untoward reaction probability of happening, thereby use tradition to contain the danger that alcoholic acid ketorolac tromethamine injection has the increase untoward reaction clinically.
Summary of the invention
In view of traditional Ketoralac ammonia butanetriol injection has above-mentioned deficiency, the present invention with a kind of phosphate buffer as solvent, provide good stability, zest littler, safer, Ketoralac ammonia butanetriol injection more easily, thereby promote the convenience of patient's medication compliance and clinical application.Ketoralac ammonia butanetriol injection of the present invention is characterised in that with phosphate buffer and replaces for example ethanol etc. of traditional solvent.
A first aspect of the present invention provides a kind of Ketoralac ammonia butanetriol injection, it is characterized in that, calculates by weight percentage, and it contains 1 to 15% ketorolac tromethamine, 0.01 to 10% buffer agent and 0.001 to 5% pH value regulator.
Percentage ratio of the present invention all is weight percentage.
Preferably, Ketoralac ammonia butanetriol injection of the present invention contains 0.5 to 8% ketorolac tromethamine, 0.05 to 5% buffer agent and and 0.01 to 2% pH value regulator.
More preferably, Ketoralac ammonia butanetriol injection of the present invention contains 1 to 5% ketorolac tromethamine, 0.1 to 3% buffer agent and 0.05 to 1% pH value regulator.
According to the present invention, described buffer agent is anhydrous or contains the phosphate solution of water of crystallization, acetate buffer, citrate buffer, triethylamine buffer solution, borate buffer solution etc., or its mixture.The preferably phosphoric acid salt buffer can contain single one or more phosphate, mixes according to different proportion.
Phosphoric acid or its esters be for example: phosphoric acid (H
3PO
4), sodium phosphate (sodium orthophosphate Na
3PO
4), sodium hydrogen phosphate (Na
2HPO
4), sodium dihydrogen phosphate (NaH
2PO
4), potassium phosphate (K
3PO
4), dipotassium hydrogen phosphate (K
2HPO
4), potassium dihydrogen phosphate (KH
2PO
4), ammonium hydrogen phosphate ((NH
4)
2HPO
4), Ammonium biphosphate (NH
4H
2PO
4), ammonium phosphate ((NH
4)
3PO
4), dalcium biphosphate (Ca (H
2PO
4)
2), calcium hydrogen phosphate (C
aHPO
4), zinc phosphate ((Z
n)
3(PO
4)
2) in waiting one or more, preferably phosphoric acid sodium (sodium orthophosphate Na
3PO
4), sodium hydrogen phosphate (Na
2HPO
4), sodium dihydrogen phosphate (NaH
2PO
4), potassium phosphate (K
3PO
4), dipotassium hydrogen phosphate (K
2HPO
4), potassium dihydrogen phosphate (KH
2PO
4) etc., more than can contain or not contain water of crystallization.
According to the present invention, described concentration anhydrous or that contain the phosphate solution of water of crystallization is 0.005-0.25mol/L, preferred 0.01-0.1mol/L.
Ketorolac tromethamine, then can produce precipitation, and be higher than at 8.5 o'clock less than 6 o'clock at pH value, then caused product and produced variable color.Therefore must add pH value regulator adjustment pH value in the Ketoralac ammonia butanetriol injection of the present invention and make it to be in 6.9-7.9.
Described pH value regulator can be selected from (1) basifier: organic base, sodium hydroxide (NaOH), potassium hydroxide (KOH), Tris (Tromethamine), ethanolamine (Monoethanolamine), potassium citrate (Pot.Citrate), triethanolamine (Triethanolamine), sodium citrate (Sod.Citrate), diethanolamine (Diethanolamine), sodium bicarbonate (Sod.Bicarlanate); (2) acidulant: organic acid, citric acid (Citric Acid), hydrochloric acid (HCl), tartaric acid, lactic acid.
Preferred pH value regulator is sodium hydroxide or hydrochloric acid.
The pH value of Ketoralac ammonia butanetriol injection of the present invention is 6.9 to 7.9, is preferably 7.2 to 7.7, meets the pH value regulation of American Pharmacopeia about Ketoralac ammonia butanetriol injection.
Except ketorolac tromethamine, buffer agent and pH value regulator, Ketoralac ammonia butanetriol injection of the present invention can also contain other additives that contained in the conventional Ketoralac ammonia butanetriol injection, for example isoosmotic adjusting agent etc.
Therefore, preferably, the composition and the content of Ketoralac ammonia butanetriol injection of the present invention are as follows:
0.1 ketorolac tromethamine to 15%;
0.01 buffer agent to 10%;
0.1 isotonic agent to 10%;
0.001 pH value regulator to 5%; With
Water adds to 100%.
According to the present invention, described isotonic agent can be at least a in sodium chloride and the potassium chloride, or other any other isotonic agents well known to those skilled in the art.
According to the present invention, described injection is used for intravenous injection or intramuscular injection.
Ketoralac ammonia butanetriol injection of the present invention is characterised in that with phosphate buffer and replaces for example ethanol etc. of traditional solvent, therefore, do not contain ethanol in the injection of the present invention.The present invention adopts sterile water for injection as solvent.
According to of the present invention one preferred embodiment, the composition and the content of Ketoralac ammonia butanetriol injection of the present invention are as follows:
Ketorolac tromethamine 3%
Potassium dihydrogen phosphate 0.5%
Sodium chloride 0.45%
PH value regulator 0.15%
Water adds to 100%.
The pH value of above-mentioned injection is 6.9-7.9.
More than comprehensive, injection of the present invention system is that binding buffer agent, pH value are adjusted agent and water for injection is formed, phosphate accounts for gross weight 0.01-10% in the buffer system, and the pH value regulator accounts for gross weight 0.001～5%, and the finished product that it made up can be made comparisons according to following project.
A second aspect of the present invention provides the method for the described Ketoralac ammonia butanetriol injection of preparation, it is characterized in that, mixes described ketorolac tromethamine, buffer agent, optional isotonic agent, pH value regulator and water.
The concrete operations step of ketorolac tromethamine aseptic injection of the present invention is as follows:
1) gets buffer agent and optional isotonic agent and add in the proper amount of water for injection, be stirred to dissolving, be mixed with buffer solution; Get ketorolac tromethamine or its salt and add an amount of water for injection and be stirred to dissolving, ketorolac tromethamine solution; Get the pH value regulator and be mixed with alkali liquor or acid solution with an amount of water for injection, standby.
2) get above-mentioned alkali liquor or the acid solution of joining the pH value of the buffer solution of being joined is adjusted to 7.2-7.7;
3) with 2) buffer of being joined adds 1) in ketorolac tromethamine solution, abundant mix homogeneously;
4) get aforementioned alkali liquor or acid solution and regulate 3) solution makes pH to 7.2-7.7, adds the injection water quantitatively to recipe quantity, mix homogeneously, get its solution with 0.22 μ m aseptic filtration, logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, 121 ℃ of temperature, 20 minutes time;
5) if be filled in the ampoule, then need carry out leak test methyl blue solution, the person then exempts from the filling small bottle;
6) carry out conventional inspection of foreign substance and comprise foreign bodies such as clarity, microgranule, cotton-wool, crystallization, utilize automatization's foreign body checking machine, it is a kind of light projecting apparatus, and its principle is promptly checked the projection of foreign body in the ampoule inner liquid medicine;
7) label;
8) packing.
The particular content of preparation method of the present invention is described as follows:
This preparation method is earlier preparation ketorolac tromethamine solution and buffer solution, adds ketorolac tromethamine solution after pH of buffer is transferred to 7.2-7.7, fully mix homogeneously.If the ketorolac tromethamine solution pH value of just joining is lower than 6 and produce muddy shape, then belong to normal phenomenon.Look its osmotic pressure, can add or not add isotonic agent, adjustment makes the requirement that meets pH value 6.9-7.9 according to actual pH again.
The specific embodiment
Embodiment 1
A: injection is formed
Ketorolac tromethamine (Ketorolac Tromethamine) 1800g
Sodium chloride (NaCl) 261g
Potassium phosphate (K
3PO
4) 445g
Potassium dihydrogen phosphate (KH
2PO
4) 41g
Sodium hydroxide (NaOH) or hydrochloric acid (HCl) q.s.
Water for injection (Water For Injection) adds to 60L
B: preparation method
1) gets phosphate and sodium chloride and add in the proper amount of water for injection, be stirred to dissolving, be mixed with phosphate solution; Get ketorolac tromethamine or its salt and add an amount of water for injection and be stirred to dissolving, ketorolac tromethamine solution; Get sodium hydroxide or hydrochloric acid and be mixed with alkali liquor or acid solution with an amount of water for injection, standby.
2) get above-mentioned alkali liquor or the acid solution of joining the pH value of the phosphate buffer of being joined is adjusted to 7.2 ± 0.1;
3) with 2) buffer of being joined adds 1) in ketorolac tromethamine solution, abundant mix homogeneously;
4) get aforementioned alkali liquor or acid solution and regulate 3) solution makes pH to 7.2 ± 0.1, adds the injection water quantitatively to recipe quantity, mix homogeneously, get its solution with 0.22 μ m aseptic filtration, logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, 121 ℃ of temperature, 20 minutes time;
The cooling wiping after, through inspection of foreign substance, get final product this finished product.
Embodiment 2
A: injection is formed
Ketorolac tromethamine (Ketorolac Tromethamine) 600g
Sodium chloride (Sodium Chloride) 261g
Sodium hydrogen phosphate (Na
2HPO
4.12H
2O) 215g
Tris (Tromethamine) or hydrochloric acid (HCl) are an amount of
Water for injection (Water For Injection) adds to 60L
B: preparation method
1) gets phosphate and sodium chloride and add in the proper amount of water for injection, be stirred to dissolving, be mixed with phosphate solution; Get ketorolac tromethamine or its salt and add an amount of water for injection and be stirred to dissolving, ketorolac tromethamine solution; Get Tris or hydrochloric acid and be mixed with alkali liquor or acid solution with an amount of water for injection, standby.
2) get above-mentioned alkali liquor or the acid solution of joining the pH value of the phosphate buffer of being joined is adjusted to 7.4 ± 0.1;
3) with 2) buffer of being joined adds 1) in ketorolac tromethamine solution, abundant mix homogeneously;
4) get aforementioned alkali liquor or acid solution and regulate 3) solution makes pH to 7.4 ± 0.1, adds the injection water quantitatively to recipe quantity, mix homogeneously, get its solution with 0.22 μ m aseptic filtration, logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, 121 ℃ of temperature, 20 minutes time;
The cooling wiping after, through inspection of foreign substance, get final product this finished product.
Embodiment 3
A: injection is formed
Ketorolac tromethamine (Ketorolac Tromethamine) 3000g
Sodium chloride (NaCl) 261g
Potassium dihydrogen phosphate (KH
2PO
4) 300g
Sodium hydroxide (NaOH) or hydrochloric acid (HCl) are an amount of
Water for injection (Water For Injection) adds to 60L
B: preparation method
1) gets phosphate and sodium chloride and add in the proper amount of water for injection, be stirred to dissolving, be mixed with phosphate solution; Get ketorolac tromethamine or its salt and add an amount of water for injection and be stirred to dissolving, ketorolac tromethamine solution; Get sodium hydroxide or hydrochloric acid and be mixed with alkali liquor or acid solution with an amount of water for injection, standby.
2) get above-mentioned alkali liquor or the acid solution of joining the pH value of the phosphate buffer of being joined is adjusted to 7.5 ± 0.1;
3) with 2) buffer of being joined adds 1) in ketorolac tromethamine solution, abundant mix homogeneously;
4) get aforementioned alkali liquor or acid solution and regulate 3) solution makes pH to 7.5 ± 0.1, adds the injection water quantitatively to recipe quantity, mix homogeneously, get its solution with 0.22 μ m aseptic filtration, logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, 121 ℃ of temperature, 20 minutes time;
The cooling wiping after, through inspection of foreign substance, get final product this finished product.
Embodiment 4
A: injection is formed
Ketorolac tromethamine (Ketorolac Tromethamine) 1800g
Sodium dihydrogen phosphate (NaH
2PO
4) 720g
Sodium hydroxide (NaOH) is an amount of
Water for injection (Water For Injection) adds to 60L
B: preparation method
1) gets phosphate and add in the proper amount of water for injection, be stirred to dissolving, be mixed with phosphate solution; Get ketorolac tromethamine or its salt and add an amount of water for injection and be stirred to dissolving, ketorolac tromethamine solution; Get sodium hydroxide and be mixed with alkali liquor with an amount of water for injection, standby.
2) get above-mentioned alkali liquor or the acid solution of joining the pH value of the phosphate buffer of being joined is adjusted to 7.5 ± 0.1;
3) with 2) buffer of being joined adds 1) in ketorolac tromethamine solution, abundant mix homogeneously;
4) get aforementioned alkali liquor or acid solution and regulate 3) solution makes pH to 7.5 ± 0.1, adds the injection water quantitatively to recipe quantity, mix homogeneously, get its solution with 0.22 μ m aseptic filtration, logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, 121 ℃ of temperature, 20 minutes time;
The cooling wiping after, through inspection of foreign substance, get final product this finished product.
Embodiment 5
A: injection is formed
Ketorolac tromethamine (Ketorolac Tromethamine) 1800g
Dipotassium hydrogen phosphate (K
2HPO
4) 470g
Sodium chloride (NaCl) 261g
Sodium hydroxide (KOH) or hydrochloric acid (HCl) are an amount of
Water for injection (Water For Injection) adds to 60L
B: preparation method
1) gets phosphate and sodium chloride and add in the proper amount of water for injection, be stirred to dissolving, be mixed with phosphate solution; Get ketorolac tromethamine or its salt and add an amount of water for injection and be stirred to dissolving, ketorolac tromethamine solution; Get sodium hydroxide or hydrochloric acid and be mixed with alkali liquor or acid solution with an amount of water for injection, standby.
2) get above-mentioned alkali liquor or the acid solution of joining the pH value of the phosphate buffer of being joined is adjusted to 7.6 ± 0.1;
3) with 2) buffer of being joined adds 1) in ketorolac tromethamine solution, abundant mix homogeneously;
4) get aforementioned alkali liquor or acid solution and regulate 3) solution makes pH to 7.6 ± 0.1, adds the injection water quantitatively to recipe quantity, mix homogeneously, get its solution with 0.22am aseptic filtration, logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, 121 ℃ of temperature, 20 minutes time;
The cooling wiping after, through inspection of foreign substance, get final product this finished product.
Embodiment 6
A: injection is formed
Ketorolac tromethamine (Ketorolac Tromethamine) 1800g
Sodium phosphate (Na
3PO4) 393g
Sodium chloride (NaCl) 261g
Sodium hydroxide (KOH) or citric acid (Citric Acid) are an amount of
Water for injection (Water For Injection) adds to 60L
B: preparation method
1) gets phosphate and sodium chloride and add in the proper amount of water for injection, be stirred to dissolving, be mixed with phosphate solution; Get ketorolac tromethamine or its salt and add an amount of water for injection and be stirred to dissolving, ketorolac tromethamine solution; Get sodium hydroxide or citric acid and be mixed with alkali liquor or acid solution with an amount of water for injection, standby.
2) get above-mentioned alkali liquor or the acid solution of joining the pH value of the phosphate buffer of being joined is adjusted to 7.3 ± 0.1;
3) with 2) buffer of being joined adds 1) in ketorolac tromethamine solution, abundant mix homogeneously;
4) get aforementioned alkali liquor or acid solution and regulate 3) solution makes pH to 7.3 ± 0.1, adds the injection water quantitatively to recipe quantity, mix homogeneously, get its solution with 0.22 μ m aseptic filtration, logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, 121 ℃ of temperature, 20 minutes time;
The cooling wiping after, through inspection of foreign substance, get final product this finished product.
Comparative Examples 1:
A: injection is formed
Ketorolac tromethamine (Ketorolac Tromethamine) 1800g
Sodium chloride (NaCl) 261g
Dehydrated alcohol 6000g
Sodium hydroxide (NaOH) is an amount of
Water for injection (Water For Injection) adds to 60L
B: preparation method
1) get ketorolac tromethamine or its salt, sodium chloride, dehydrated alcohol adds an amount of water for injection (about 85% recipe quantity) and is stirred to dissolving, ketorolac tromethamine solution; Get sodium hydroxide and be mixed with alkali liquor with an amount of water for injection, standby.
2) with sodium hydroxide solution the pH of ketorolac tromethamine solution is transferred to 7.4 ± 0.1;
3) add the injection water quantitatively to recipe quantity, mix homogeneously is got its solution with 0.22 μ m aseptic filtration, and logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, and 121 ℃ of temperature, 20 minutes time;
The cooling wiping after, through inspection of foreign substance, get final product this finished product.
Comparative Examples 2:
A: injection is formed
Ketorolac tromethamine (Ketorolac Tromethamine) 1800g
Dehydrated alcohol 5400g
1,2-propylene glycol 12L
Sodium hydroxide (NaOH) is an amount of
Water for injection (Water For Injection) adds to 60L
B: preparation method
1) get ketorolac tromethamine or its salt, dehydrated alcohol and 1, the 2-propylene glycol adds an amount of water for injection (about 85% recipe quantity) and is stirred to dissolving, gets ketorolac tromethamine solution; Get sodium hydroxide and be mixed with alkali liquor with an amount of water for injection, standby.
2) with sodium hydroxide solution the pH of ketorolac tromethamine solution is transferred to 7.3 ± 0.1;
3) add the injection water quantitatively to recipe quantity, mix homogeneously is got its solution with 0.22 μ m aseptic filtration, and logical nitrogen was filled in the appropriate containers after 10 minutes, then with its autoclaving, and 121 ℃ of temperature, 20 minutes time;
The cooling wiping after, through inspection of foreign substance, get final product this finished product.
The study on the stability test
1. sample preparation
By each 1 batch of the formulation and technology pilot sample of embodiment of the invention 1-6 and Comparative Examples 1-2, totally 8 batches, 40,000 every batch, lot number is respectively: RP001, RP002, RP003, RP004, RP005, RP006, D001, D002 all meet the requirements through checking each batch sample.
2. pilot project
2.1 hot test and exposure experiments to light
Press Chinese Pharmacopoeia (2005 editions) appendix XIX C crude drug and pharmaceutical preparation stability test guideline, sample is removed outer package, learnt from else's experience and examined qualified ketorolac tromethamine injection entirely, place strong illumination (4500 ± 500Lx) respectively, high temperature (60 ℃) was placed 10 days down, the sampling and measuring respectively in the 5th day and 10 days, and with 0 day with the contrast of batch sample data, the results are shown in Table 1 with table 2.
As can be seen from Table 1, this product is being removed outer package, places 10 days under 60 ℃ of hot conditionss, and its appearance characteristics, pH value, related substance and content have no significant change.
As can be seen from Table 2, this product is being removed outer package, and (its related substances slightly raises under 4500 ± 500Lx) conditions, but still in prescribed limit in strong illumination.Investigate result of the test by illumination and temperatures involved factor and show that injection liquid samples is basicly stable to heat, light, adopt ordinary packing according to above experimental result explanation this product, shading is stored and is got final product.
2.2 accelerated test
Press Chinese Pharmacopoeia (2005 editions) appendix XIX C crude drug and pharmaceutical preparation stability test guideline, to place in the climatic chamber of 40 ℃ ± 2 ℃ of temperature, relative humidity RH75% ± 5% through the qualified ketorolac tromethamine injection of full inspection and store six months, each sampling is once checked the 1st, 2,3,6 the end of month, and with 0 day with batch sample data contrasts, the results are shown in Table 3.
Result of the test shows, and compares before the test, and the pH value of this injection is basicly stable, changes within normal range, and active substance and active constituent content are basicly stable.
2.3 long term test
Press Chinese Pharmacopoeia (2005 editions) appendix XIX C crude drug and pharmaceutical preparation stability test guideline, to place under 25 ℃ ± 2 ℃ of temperature, relative humidity RH60% ± 10% condition through the qualified ketorolac tromethamine injection of full inspection and place 24 months, each sampling is once checked the 1st, 3,6,9,12,24 the end of month, and in 0 day with batch sample data contrasts, the results are shown in Table 4.
Result of the test shows that the pH value of this injection is basicly stable, changes very for a short time, and within normal range, related substance and active component content change very little, up to specification, have good stability.
3. conclusion (of pressure testing)
Ketorolac tromethamine injection of the present invention shows under the condition of exposure experiments to light, hot test, accelerated test, long term test in above influence factor's experimental result, the basicly stable property of its pH value is good, active component content does not have significant change, its related substances increases to some extent, but still within the scope of regulation.Therefore, compare with the ketorolac tromethamine injection that contains ethanol or propylene glycol of prior art, the stability of ketorolac tromethamine injection of the present invention is suitable with it, but toxicity, zest have but reduced, and can with injection of morphia agent compatibility.
Claims (20)
1. a Ketoralac ammonia butanetriol injection is characterized in that, calculates by weight percentage, and it contains 0.1 to 15% ketorolac tromethamine, 0.01 to 10% buffer agent and 0.001 to 5% pH value regulator.
2. Ketoralac ammonia butanetriol injection according to claim 1 is characterized in that, calculates by weight percentage, and it contains 0.5 to 8% ketorolac tromethamine, 0.05 to 5% buffer agent and 0.01 to 2% pH value regulator.
3. Ketoralac ammonia butanetriol injection according to claim 2 is characterized in that, calculates by weight percentage, and it contains 1 to 5% ketorolac tromethamine, 0.1 to 3% buffer agent and 0.05 to 1% pH value regulator.
4. according to the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 3, it is characterized in that described buffer agent is anhydrous or contains the phosphate of water of crystallization, acetate, citrate, triethylamine buffer solution, borate buffer solution, or its mixture.
5. Ketoralac ammonia butanetriol injection according to claim 4 is characterized in that, described buffer agent is anhydrous or contains the phosphate solution of water of crystallization.
6. Ketoralac ammonia butanetriol injection according to claim 5 is characterized in that, described concentration anhydrous or that contain the phosphate solution of water of crystallization is 0.005-0.25mol/L.
7. Ketoralac ammonia butanetriol injection according to claim 6 is characterized in that, described phosphatic concentration anhydrous or that contain water of crystallization is 0.01-0.1mol/L.
8. the arbitrary described Ketoralac ammonia butanetriol injection of claim 4 to 7, it is characterized in that described phosphate anhydrous or that contain water of crystallization is selected from one or more in sodium dihydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium phosphate, tripotassium phosphate, dibastic sodium phosphate, potassium hydrogen phosphate, ammonium hydrogen phosphate, Ammonium biphosphate, ammonium phosphate, dalcium biphosphate, calcium hydrogen phosphate or the zinc phosphate.
9. the described Ketoralac ammonia butanetriol injection of claim 8, it is characterized in that described phosphate anhydrous or that contain water of crystallization is selected from least a in sodium dihydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium phosphate, tripotassium phosphate, dibastic sodium phosphate or the potassium hydrogen phosphate.
10. according to the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 9, it is characterized in that described pH value regulator is selected from sodium hydroxide, potassium hydroxide, Tris, ethanolamine, potassium citrate, triethanolamine, sodium citrate, diethanolamine, sodium bicarbonate, citric acid, hydrochloric acid, tartaric acid or lactic acid.
11., it is characterized in that described pH value regulator is selected from sodium hydroxide or hydrochloric acid according to the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 10.
12., it is characterized in that it also contains 0.1 to 10% isotonic agent according to the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 11.
13. Ketoralac ammonia butanetriol injection according to claim 12 is characterized in that, described isotonic agent is selected from least a in sodium chloride and the potassium chloride.
14., it is characterized in that the pH value of described injection is 6.9 to 7.9 according to the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 13.
15. Ketoralac ammonia butanetriol injection according to claim 14 is characterized in that, the pH value of described injection is 7.2 to 7.7.
16., it is characterized in that described injection is used for intravenous injection or intramuscular injection according to the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 15.
17. according to the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 16, it is characterized in that, do not contain ethanol in the described injection.
18. according to the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 16, it is characterized in that, described injection with water as solvent.
19. the Ketoralac ammonia butanetriol injection according to claim 12 is characterized in that, calculates by weight percentage, its composition and content are as follows:
Ketorolac tromethamine 3%
Potassium dihydrogen phosphate 0.5%
Sodium chloride 0.45%
PH value regulator 0.15%
Water adds to 100%.
20. preparation is characterized in that according to the method for the arbitrary described Ketoralac ammonia butanetriol injection of claim 1 to 19, mixes described ketorolac tromethamine, buffer agent, optional isotonic agent, pH value regulator and water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101153684A CN102138891A (en) | 2010-01-28 | 2010-01-28 | Ketorolac tromethamine injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101153684A CN102138891A (en) | 2010-01-28 | 2010-01-28 | Ketorolac tromethamine injection |
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| Publication Number | Publication Date |
|---|---|
| CN102138891A true CN102138891A (en) | 2011-08-03 |
Family
ID=44406837
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101153684A Pending CN102138891A (en) | 2010-01-28 | 2010-01-28 | Ketorolac tromethamine injection |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830171A (en) * | 2014-03-04 | 2014-06-04 | 鲁南制药集团股份有限公司 | Ketorolac tromethamine injection and preparation method thereof |
| CN107854429A (en) * | 2017-12-25 | 2018-03-30 | 南京正科医药股份有限公司 | A kind of dexketoprofen trometamol parenteral solution and its preparation technology |
| CN111481501A (en) * | 2020-05-19 | 2020-08-04 | 南京锐志生物医药有限公司 | Ketorolac tromethamine injection capable of reducing irritation and free of organic solvent |
| CN113384524A (en) * | 2021-07-05 | 2021-09-14 | 四川尚锐生物医药有限公司 | Preparation method of stable ketorolac tromethamine injection |
| CN113679676A (en) * | 2020-05-19 | 2021-11-23 | 南京海融医药科技股份有限公司 | Pharmaceutical composition of levoketorolac and preparation method thereof |
| CN114191384A (en) * | 2021-12-20 | 2022-03-18 | 成都倍特药业股份有限公司 | Instant ketorolac tromethamine and etazocine hydrobromide combined liquid preparation |
| CN115518035A (en) * | 2021-06-24 | 2022-12-27 | 上海博志研新药物技术有限公司 | Ketorolac liquid composition, preparation method and application thereof |
-
2010
- 2010-01-28 CN CN2010101153684A patent/CN102138891A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830171A (en) * | 2014-03-04 | 2014-06-04 | 鲁南制药集团股份有限公司 | Ketorolac tromethamine injection and preparation method thereof |
| CN103830171B (en) * | 2014-03-04 | 2015-11-18 | 鲁南制药集团股份有限公司 | A kind of Ketorolac tromethamine injection and preparation method thereof |
| CN107854429A (en) * | 2017-12-25 | 2018-03-30 | 南京正科医药股份有限公司 | A kind of dexketoprofen trometamol parenteral solution and its preparation technology |
| CN111481501A (en) * | 2020-05-19 | 2020-08-04 | 南京锐志生物医药有限公司 | Ketorolac tromethamine injection capable of reducing irritation and free of organic solvent |
| CN113679676A (en) * | 2020-05-19 | 2021-11-23 | 南京海融医药科技股份有限公司 | Pharmaceutical composition of levoketorolac and preparation method thereof |
| CN111481501B (en) * | 2020-05-19 | 2022-04-29 | 南京锐志生物医药有限公司 | Ketorolac tromethamine injection capable of reducing irritation and free of organic solvent |
| CN115518035A (en) * | 2021-06-24 | 2022-12-27 | 上海博志研新药物技术有限公司 | Ketorolac liquid composition, preparation method and application thereof |
| CN115518035B (en) * | 2021-06-24 | 2024-02-27 | 上海云晟研新生物科技有限公司 | Ketorolac liquid composition, preparation method and application thereof |
| CN113384524A (en) * | 2021-07-05 | 2021-09-14 | 四川尚锐生物医药有限公司 | Preparation method of stable ketorolac tromethamine injection |
| CN114191384A (en) * | 2021-12-20 | 2022-03-18 | 成都倍特药业股份有限公司 | Instant ketorolac tromethamine and etazocine hydrobromide combined liquid preparation |
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