Ketoprofen solution and preparation method thereof

Abstract

The invention discloses a ketoprofen solution. The ketoprofen solution comprises the following components in every 100mL: 0.1-1g of ketoprofen, 0.1-10g of sodium acetate, glacial acetic acid used for regulating the pH value to 5.5-6.5, and the balance of injection water. A preparation method of the ketoprofen solution comprises the following steps: adding the sodium acetate with the prescribed amount into 50-80mL of injection water, uniformly stirring and mixing; adding ketoprofen with the prescribed amount into the mixture, stirring under a condition of 50+ / -5 DEG C until the ketoprofen is completely dissolved; cooling the liquid medicine to room temperature, and regulating the pH value to 5.5-6.5 with glacial acetic acid; fixing the volume to 100mL by using the injection water, uniformly mixing, and filtering. According to the ketoprofen solution, the sodium acetate is used as a cosolvent of ketoprofen, so that the defect of an existing ketoprofen cosolvent can be overcome; the sodium acetate and the glacial acetic acid or ketoprofen form a buffering pair, and play an important role in stabilizing the pH value of the solution; the ketoprofen solution is simple in preparation process, good in repeatability and low in cost, is suitable for industrial large-scale production, does not contain an organic solvent, benzyl alcohol or other component, is safer in clinical application, can be produced into an oral solution and small-dose injection, as well as a preparation for venous transfusion.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and relates to a ketoprofen preparation and a preparation method thereof. Background technique [0002] Ketoprofen (ketoprofen), also known as ketoprofen, chemical name is 3-benzoyl-α-methylphenylacetic acid, almost insoluble in water, easily soluble in methanol, soluble in ethanol, acetone or ether. Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAIDs), and is recognized as one of the safest drugs among NSAIDs, with anti-inflammatory, analgesic and antipyretic effects, clinically used for surgery. Post-traumatic pain, acute renal colic, various mild and moderate cancer pains (severe cancer pain can be used as an adjunct to opioid analgesics), pain caused by gout attacks, rheumatic and rheumatoid arthritis, rigidity spondylitis, osteoarthritis, etc. According to the three-step analgesic method recommended by the World Health Organization (WHO), NSAIDs s...

AI Technical Summary

Problems solved by technology

However, CO2 will be generated when the injection is diluted with acidic solution such as normal saline or 5% glucose injection. 2 Gas, if the exhaust operation is improper, it may cause the pollution of the liquid medicine, if the CO infusion process 2 Air bubbles entering the patient's blood may form a gas embolism

[0005] Chinese patent application CN1376670A prepares ketoprofen and arginine into freeze-dried powder after chemical reaction to generate double salt. Not only the production process is complicated, vacuum freeze-drying technology and equipment are needed, the production cost is high, and more importantly, due to The product has a high alkalinity, and it is easy to precipitate crystals in neutral or slightly acidic injection solvents such as sodium chloride solution or glucose solution

But this method is only applicable to dexketoprofen, and the current commercially available dexketoprofen raw material is oral grade, and it is easy to produce uncontrollable consequences by making it into preparation and direct intravenous injection. Therefore, oral grade dexketoprofen is needed Refining (recrystallization with organic solvent) of ketoprofen bulk drug will not only increase production cost, time-consuming and labor-intensive, but also may increase environmental pollution

[0008] Chinese patent application CN1621034A and CN1264505C disclose a kind of ketoprofen freeze-dried powder injection, adopt sodium hydroxide as cosolvent, and it is more irritating to human body when injection is used

Moreover, compared with solution-type injections, the production process of freeze-dried powder injections is complicated, and the production environment and equipment requirements are high; non-terminal sterilized products have a low level of sterility assurance; they need to be dissolved in injection solvents before use, which is inconvenient and Increase the chance of infection

[0009] Chinese patent application CN1709232A prepares ketoprofen or ketoprofen axetil into an injectable lipid microsphere emulsion, not only the preparation process is complicated, the cost is high, but also the production difficulty is large, and the emulsion droplet size and its dispersion uniformity are difficult to control. Emulsions are prone to changes such as stratification, flocculation, phase inversion, merger, rupture and rancidity during storage

Wherein, both ketoprofen arginine injection and ketoprofen lysine injection contain benzyl alcohol, which has analgesic effect, but is prone to adverse reactions such as hemolysis. Therefore, the above two injections are only suitable for intramuscular injection. rather than intravenous infusion

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