A kind of ketorolac tromethamine injection that reduces irritation and does not contain organic solvents

Abstract

The invention provides a ketorolac tromethamine injection that reduces irritation and does not contain organic solvents. By using the tromethamine-acidulant buffer system as a protective agent, the adverse effects of ethanol and potassium dihydrogen phosphate on the packaging material and the serious irritation at the injection site in the prior art are avoided. The production process of the invention is simple and controllable, the physical and chemical properties of the medicinal liquid are relatively stable, and the drug safety and compliance of patients can be improved.

Description

technical field [0001] The invention relates to a ketorolac tromethamine injection, in particular to a ketorolac tromethamine injection which reduces irritation and does not contain an organic solvent, and belongs to the field of pharmaceutical preparations. Background technique [0002] Ketorolac tromethamine is a non-steroidal anti-inflammatory drug, mainly by reducing the activity of peripheral cyclooxygenase and prostaglandin synthase, thereby reducing the effect of endogenous inflammatory factors on nociceptive fine fibers (such as A-δ and C) stimulation and excitatory effects, so as to achieve the therapeutic effect of pain relief and anti-inflammation. This product rarely occurs central nervous system adverse reactions such as respiratory depression, and does not act on opioid receptors or stimulate the release of opioid peptides in the body. Therefore, it is a relatively safe drug that can replace opioids to a certain extent. Short-term treatment of acute moderate t...

AI Technical Summary

Problems solved by technology

It can be seen that the formulations disclosed in the above patents cannot fully meet the clinical requirements, and the marketed ketorolac tromethamine injection still has the following technical problems:

[0005] 1) When patients are injected with potassium-containing solutions, the excessively high extracellular concentration of potassium ions will stimulate nerve fiber cells on the blood vessel wall, resulting in swelling of endothelial cells, vasospasm, and strong pain in patients. For those with poor blood vessel walls For the elderly, the pain will be more obvious; and for the inner packaging container made of glass, phosphate has certain compatibility risks, such as delamination, elemental impurities, particles, etc.

[0006] 2) The ethanol formula using organic solvents requires more production process control and finished product testing due to its volatile characteristics, which affects manufacturing costs and efficiency; in addition, for products containing a large amount of ethanol, although the existing packaging is airtight and complete Sexuality control measures can guarantee the sterility of the product, but it cannot completely avoid the volatilization of ethanol during long-term storage. Without the solubilization of ethanol, ketorolac tromethamine may precipitate to varying degrees, and the precipitates are insoluble particles, or even white point

[0007] 3) The ethanol formula does not contain a buffer system with a certain protective effect. During storage, a reaction may occur between the liquid medicine and the ampoule bottle of suboptimal quality, so that harmful substances in the glass of the ampoule bottle are immersed in the liquid medicine, thereby increasing The safety risk of the liquid medicine;

[0008] 4) In clinical use, ethanol is more irritating, especially intramuscular injection; when used in combination with morphine and other injections, ethanol has a certain impact on the absorption and metabolism of morphine, increasing the probability of adverse reactions; when used in combination with cephalosporin antibiotics, A disulfiram reaction can occur, resulting in a drop in blood pressure, rapid heartbeat, or partial changes in the ECG

Therefore, the ketorolac tromethamine injection containing ethanol has certain unsafety

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