阅读说明：本技术 一种用于治疗复杂性***的注射液及其制备方法 (Injection for treating complicated urinary tract infection and preparation method thereof ) 是由 孙亚敏 李锡勇 刘振华 董济军 于 2020-05-21 设计创作，主要内容包括：本发明属于医药技术领域,具体涉及一种用于治疗复杂性尿路感染的注射液及其制备方法。一种用于治疗复杂性尿路感染的注射液主要由活性成分plazomicin sulfate、硫代硫酸钠、稀醋酸溶液和注射用水组成。本发明制备的用于治疗复杂性尿路感染的注射液提高了活性成分plazomicin sulfate在处方中的溶解度,节约了制剂制备过程中的生产成本,方便了产品的运输,同时也给临床用药带来了便利。(The invention belongs to the technical field of medicines, and particularly relates to an injection for treating complicated urinary tract infection and a preparation method thereof. An injection for treating complicated urinary tract infection is prepared from the active component of prazomicin sulfate, sodium thiosulfate, diluted acetic acid solution and water for injection. The injection for treating complicated urinary tract infection, prepared by the invention, improves the solubility of the active ingredient, namely the prazomicin sulfate, in a prescription, saves the production cost in the preparation process of the preparation, facilitates the transportation of the product and brings convenience to clinical medication.)

1. An injection for treating complicated urinary tract infection is characterized by mainly comprising active ingredients of placomicinsufate, sodium thiosulfate, dilute acetic acid solution and water for injection.

2. The injection according to claim 1, wherein the concentration of the active ingredient, namely the placomicin sulfate, is 200-300 mg/ml.

3. The injection according to claims 1 and 2, wherein the concentration of the active ingredient, namely the plasmomicin sulfate, is 250 mg/ml.

4. The injection according to claim 1, wherein the concentration of the sodium thiosulfate is 1.5 to 2.5 mg/ml.

5. The injection according to claims 1 and 4, wherein the concentration of sodium thiosulfate is 2.0 mg/ml.

6. The injection according to claim 1, wherein the pH value of the injection is in the range of 3.5 to 4.5.

7. The injection according to claims 1 and 6, wherein the pH of the injection is 4.0.

8. The injection according to claim 1, wherein the pH regulator is a dilute acetic acid solution.

9. A preparation method of an injection for treating complicated urinary tract infection comprises the following steps:

weighing sodium thiosulfate and a azomicin sulfate in a formula amount, dissolving the sodium thiosulfate and the azomicin sulfate in water for injection accounting for 50-60% of the total volume, heating to 55-65 ℃, and stirring for dissolving for 10-16 min; cooling to room temperature, adjusting pH with appropriate amount of dilute acetic acid solution, diluting to desired volume with injectable water, stirring, mixing and dissolving; filtering, bottling, sterilizing, and inspecting by eye to obtain the final product.

10. The preparation method of the injection for treating complicated urinary tract infection according to claim 9, wherein the preparation process comprises the following steps: weighing sodium thiosulfate and a plastomicin sulfate in a prescription amount, dissolving the sodium thiosulfate and the plastomicin sulfate in water for injection accounting for 55% of the total volume, heating to 60 ℃, and stirring for dissolving for 13 min; cooling to room temperature, adjusting pH with appropriate amount of dilute acetic acid solution, diluting to desired volume with injectable water, stirring, mixing and dissolving; filtering, bottling, sterilizing, and inspecting by eye to obtain the final product.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to an injection for treating complicated urinary tract infection and a preparation method thereof.

Background

Complicated urinary tract infection refers to serious injury of renal function caused by repeated or sustained urinary tract infection when there is anatomical or functional abnormality (such as obstruction, calculus, etc.) or renal exogenous concomitant diseases (such as diabetes, abuse of phenacetin-containing analgesic, sickle cell disease, etc.).

More than 95% of urinary tract infections are caused by a single bacterium. Among them, 90% of outpatients and about 50% of inpatients have pathogenic bacteria of Escherichia coli, and the serotyping of the pathogenic bacteria can reach more than 140, so that the urine-sensitive Escherichia coli and the Escherichia coli separated from the feces of the patients belong to the same bacterial type, and are mostly seen in asymptomatic bacteriuria or urine sensation without complications; proteus, aerobacter, Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus faecalis, etc. are seen in re-infection, indwelling catheter, and urinary sensation with complications; candida albicans and cryptococcus neoformans infections are frequently seen in patients with diabetes and using glucocorticoids and immunosuppressive drugs and after kidney transplantation; staphylococcus aureus is commonly seen in bacteremia and septicemia caused by skin wounds and drug addicts, and virus and mycoplasma infection is rare and tends to increase in recent years. Various bacterial infections are found in indwelling catheters, neurogenic bladders, stones, congenital malformations and fistulas in the vagina, intestines, urethra, etc.

The plazomicin is a new generation of aminoglycoside antibiotics, and can inhibit the translation process of bacterial proteins. The plazomicin is obtained by carrying out chemical modification on the basis of sisomicin (sisomicin), and can avoid the loss of activity caused by the damage of main aminoglycoside antibiotic inactivating enzyme (AME). The plazomicin was developed for the treatment of severe infections caused by MDR gram negative bacteria enterobacteriaceae, including enterobacteriaceae that are resistant to carbapenem antibiotics.

Achaogen obtained FDA in the united states and EMA in the european union, approved us zemdri (placomicin) for adult patients with complicated urinary tract infections (cluti, including pyelonephritis) caused by certain enterobacteriaceae bacterial infections with very limited or no treatment options, respectively, 6 months 2018. Based on the data from phase III clinical studies with EPIC, Zemdri achieved non-inferior efficacy with meropenem (meropenm).

Plazomicin sulfate

Chemical name: (2"R,3"R,4"R,5"R)-2"-[(1S,2S,3R,4S,6R)-4-amino-6-[(2'"S)-4'"-amino-2'"-hydrox-

ybutan amido)amino]-3-[(2'S,3'R)-3'-amino-6'-((2-hydroxyethylamino)methyl)-3',4'-dihydro-2H

-pyran-2'-yloxy]-2-hydroxycyclohexyloxy]-5''-methyl-4''-(methylamino)tetrahydro-2H-pyran-3'',5''-diol sulfate

The molecular formula is as follows: c₂₅H₄₈N₆O₁₀∙2.5H₂SO₄

Molecular weight: 837.89

The molecular structure is as follows:

the U.S. FDA approved zemdri (placomicin) by achalogen corporation also publishes its prescription, which consists of:

plasmicin sulfate (in a plasmicin freebase)	50g
		Adjusting the pH value of the sodium hydroxide solution	6.5
The injection water is constant volume	1000ml

The inventor finds in experiments that the concentration of the zemdri (placomicin) injection of Achaogen company is 50mg/ml and the filling amount is 10ml, so that the production cost is greatly increased, and the inconvenience is brought to transportation.

Disclosure of Invention

In view of the current disadvantages, the present invention provides an injection for treating complicated urinary tract infection: mainly comprises an active ingredient of the azomicin sulfate, sodium thiosulfate, dilute acetic acid solution and water for injection.

The injection provided by the invention comprises the following components: the concentration of the active ingredient, namely the prazomicin sulfate, is 200-300 mg/ml, and preferably 250 mg/ml.

The injection provided by the invention comprises the following components: the concentration of the sodium thiosulfate is 1.5-2.5 mg/ml, and preferably 2.0 mg/ml.

The injection provided by the invention comprises the following components: the pH value regulator is a dilute acetic acid solution, and the pH value is 3.5-4.5, preferably 4.0.

The invention further provides a preparation method of the injection for treating complicated urinary tract infection, which comprises the following steps:

(1) weighing sodium thiosulfate and a azomicin sulfate in a formula amount, dissolving the sodium thiosulfate and the azomicin sulfate in water for injection accounting for 50-60% of the total volume, heating to 55-65 ℃, and stirring for dissolving for 10-16 min;

(2) cooling to room temperature, adjusting pH with appropriate amount of dilute acetic acid solution, diluting to desired volume with injectable water, stirring, mixing and dissolving;

(3) filtering, bottling, sterilizing, and inspecting by eye to obtain the final product.

The preparation method provided by the invention further preferably comprises the following steps:

(1) weighing sodium thiosulfate and a plastomicin sulfate in a prescription amount, dissolving the sodium thiosulfate and the plastomicin sulfate in water for injection accounting for 55% of the total volume, heating to 60 ℃, and stirring for dissolving for 13 min;

(2) cooling to room temperature, adjusting pH with appropriate amount of dilute acetic acid solution, diluting to desired volume with injectable water, stirring, mixing and dissolving;

(3) filtering, bottling, sterilizing, and inspecting by eye to obtain the final product.

Compared with the prior art, the injection for treating complicated urinary tract infection and the preparation method thereof have the following advantages: the formula is stable, the process is simple, and the reasonability of the formula process is proved through accelerated test investigation; meanwhile, the invention improves the solubility of the active ingredient of the prazomicin sulfate in the prescription through the optimization of the prescription process, saves the production cost in the preparation process of the preparation, facilitates the transportation of the product and brings convenience to clinical medication.

Detailed Description