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

A technology of ketorolac tromethamine and ketorolac tromethamine, which is applied in the field of ketorolac tromethamine injection, can solve the problems of patients with strong pain, vasospasm, and obvious pain, and achieve insoluble particles and Reduced white spots, reduced risk of vascular embolism, and improved overall quality

Active Publication Date: 2022-04-29
南京锐志生物医药有限公司
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  • Abstract
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  • Claims
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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

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] A: Prescription composition

[0096] Ketorolac tromethamine 10g trometamol 11.78g Sodium chloride 2.70g hydrochloric acid Appropriate amount, adjusted to pH about 7.3 Water for Injection to 1L batch 1000 pieces

[0097] B: Preparation method:

[0098] 1. Add tromethamine and sodium chloride into 95% prescription water for injection cooled to room temperature, and stir until completely dissolved;

[0099] 2. Add ketorolac tromethamine and stir until completely dissolved;

[0100] 3. Add 1M hydrochloric acid aqueous solution to adjust the pH of the liquid to about 7.26;

[0101] 4. Use the remaining amount of water for injection to adjust the concentration of ketorolac tromethamine to 10 mg / mL;

[0102] 5. The liquid medicine is filtered through a 0.2μm filter element to the buffer tank of the filling machine;

[0103] 6. Under the protection of nitrogen, fill the liquid medicine into the cleaned and dry heat sterilized gla...

Embodiment 2

[0108] A: Prescription composition

[0109]

[0110]

[0111] B: Preparation method:

[0112] 1. Add tromethamine and sodium chloride into 95% prescription water for injection cooled to room temperature, and stir until completely dissolved;

[0113] 2. Add ketorolac tromethamine and stir until completely dissolved;

[0114] 3. Add 1M hydrochloric acid aqueous solution to adjust the pH of the liquid to about 7.29;

[0115] 4. Use the remaining amount of water for injection to adjust the concentration of ketorolac tromethamine to 15 mg / mL;

[0116] 5. The liquid medicine is filtered through a 0.2μm filter element to the buffer tank of the filling machine;

[0117] 6. Under the protection of nitrogen, fill the liquid medicine into the cleaned and dry heat sterilized glass ampoule, and seal it;

[0118] 7. Moist heat sterilization, F 0 ≥12;

[0119] 8. Inspection and elimination of unqualified products;

[0120] 9. Outsource the labeling of qualified products.

Embodiment 3

[0122] A: Prescription composition

[0123] Ketorolac tromethamine 30g trometamol 2.46g Sodium chloride 4.03g hydrochloric acid Appropriate amount, adjusted to pH about 7.3 Water for Injection to 1L batch 1000 pieces

[0124] B: Preparation method:

[0125] 1. Add tromethamine and sodium chloride into 95% prescription water for injection cooled to room temperature, and stir until completely dissolved;

[0126] 2. Add ketorolac tromethamine and stir until completely dissolved;

[0127] 3. Add 1M hydrochloric acid aqueous solution to adjust the pH of the liquid to about 7.32;

[0128] 4. Use the remaining amount of water for injection to adjust the concentration of ketorolac tromethamine to 30mg / mL;

[0129] 5. The liquid medicine is filtered through a 0.2μm filter element to the buffer tank of the filling machine;

[0130] 6. Under the protection of nitrogen, fill the liquid medicine into the cleaned and dry heat sterilized gla...

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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...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/08A61K31/407A61K47/18A61P29/00
CPCA61K31/407A61K47/18A61K9/08A61K9/0019A61P29/00
Inventor 孙蕴哲沙向阳郑枫
Owner 南京锐志生物医药有限公司
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