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CN-121987793-A - Injection for treating ICU severe and cancer postoperative patients delirium, and preparation method and application thereof

CN121987793ACN 121987793 ACN121987793 ACN 121987793ACN-121987793-A

Abstract

The invention discloses an injection for preventing and treating ICU severe and cancer postoperative patients from delirium, and a preparation method and application thereof, and belongs to the technical field of medicinal preparations. The injection comprises 0.0010.5% of melatonin receptor agonist, 530% of injection oil, 0.55% of phospholipid, 00.5% of auxiliary emulsion, 0.55% of isotonic regulator, 0.011.0% of pH regulator, and the balance of water for injection, wherein the pH is 5.010.0. The preparation process comprises the steps of oil phase preparation, water phase preparation, emulsification, high-pressure homogenization, sterilization and the like. The injection has average particle diameter (D50) of 100350nm, large emulsion particle of 5 μm of 0% -0.05%, release degree within 1 hr not less than 80%, and main medicine content within 24 months effective period not less than 90%. The invention realizes the accessibility of the existing ICU critical illness and the drug treatment for delirium after cancer operation. The medicine has rapid onset of action after administration, can realize smooth transition of short-term injection administration after ICU/severe operation and oral administration in the recovery period, and has remarkable clinical compliance advantage.

Inventors

  • DONG YANBIN
  • CHEN KAIJUN
  • YIN LEI
  • HUANG JIANGUO
  • CAI WEI
  • ZHANG YINGYE
  • LU MINFEI
  • HUANG JILONG

Assignees

  • 广东国标医药科技有限公司

Dates

Publication Date
20260508
Application Date
20260203

Claims (10)

  1. 1. An injection for preventing and treating delirium of patients after ICU severe and cancer operation is characterized by mainly comprising the following components in percentage by weight: 0.001% to 0.5% melatonin receptor agonist; 5.0% to 30.0% of an oil for injection; 0.5% to 5.0% of a phospholipid; 0% to 0.5% of a co-emulsion; 0.5% to 5.0% of an isotonicity adjusting agent; 0.01% to 1.0% of a pH adjuster; The balance of water for injection; The pH value of the injection is 5.0 to 10.0.
  2. 2. The injection according to claim 1, wherein the melatonin receptor agonist is ramelteon or tasimelteon.
  3. 3. The injection according to claim 1, wherein the injectable oil is at least one of soybean oil, medium-chain oil, olive oil, and fish oil, and the phospholipid is at least one of egg yolk lecithin and soybean lecithin.
  4. 4. The injection according to claim 1, wherein the emulsion aid is at least one of oleic acid and sodium oleate.
  5. 5. The injection according to claim 1, wherein the volume average particle diameter D50 of the injection is 100nm to 350nm.
  6. 6. The injection according to any one of claims 1 to 5, wherein the proportion of milk particle volume with particle size greater than 5 μm in the injection to total milk volume is less than 0.05%.
  7. 7. The injection according to any one of claims 1 to 6, wherein the injection is in a phosphate buffer release medium at 37 ° C, pH 7.4.4 in vitro, and the cumulative release of melatonin receptor agonist over 1 hour is not less than 80%.
  8. 8. A method for preparing the injection according to any one of claims 1 to 7, comprising the steps of: (a) Forming an oil phase by shear mixing the melatonin receptor agonist, the injectable oil, the phospholipid and optionally the co-emulsion; (b) Dissolving the isotonic regulator and the pH regulator in part of water for injection to form an aqueous phase; (c) Mixing the oil phase and the water phase and performing high-speed shearing emulsification to obtain coarse emulsion; (d) Homogenizing the crude milk under high pressure to obtain refined milk; (e) And supplementing the water for injection to the full amount, filtering, filling and sterilizing to obtain a finished product.
  9. 9. The method of claim 8, wherein the high pressure homogenization treatment pressure in step (d) is from 200 bar to 1500 bar and the number of homogenization is from 1 to 10.
  10. 10. Use of an injection according to any one of claims 1 to 7 for the preparation of a medicament for the prevention and/or treatment of ICU severe, cancer postoperative delirium in patients.

Description

Injection for treating ICU severe and cancer postoperative patients delirium, and preparation method and application thereof Technical Field The invention relates to the technical field of medicinal preparations, in particular to an injection and a preparation method thereof, and application of the injection in preparing medicaments for preventing and/or treating ICU severe diseases and delirium of patients after cancer operation. Background Delirium is a common and severe acute brain dysfunction syndrome characterized by acute, fluctuating disturbances of attention and conscious levels, with altered cognitive function or sensory impairment. The incidence of this disease is markedly increased in clinical settings, especially in Intensive Care Units (ICU) and in patients undergoing major surgical procedures such as cardiovascular surgery, oncology. According to clinical guidelines such as "expert consensus for prevention and cure of delirium after operation" of elderly patients in China, delirium not only leads to prolonged hospitalization time and sharp increase of medical cost of patients, but also increases independent risk factors of postoperative complications, long-term decline of cognitive function and death rate of illness, and constitutes a heavy burden for patients in prognosis and medical systems. Currently, there is no formally approved specific therapeutic drug for ICU severe and cancer postoperative patients. The clinical practice generally has the phenomenon of drug administration beyond the specification, and often depends on the intervention of drugs such as benzodiazepine sedatives, atypical antipsychotics and the like. The strategy has obvious limitations that firstly, the curative effect lacks high-level evidence-based medical evidence support and is inaccurate in intervention on a core pathophysiological link of delirium, and secondly, the medicine possibly brings serious adverse reactions such as excessive sedation, respiratory depression, cardiovascular events, extrapyramidal reactions and the like, and the application risk is particularly prominent in perioperative patients with complicated conditions. Therefore, developing a safe, effective and specific therapeutic means suitable for treating ICU severe and cancer postoperative delirium is a critical problem to be solved in clinic. Melatonin receptor agonists (such as ramelteon and tasimelteon) show unique therapeutic potential in the pathophysiological links of delirium by regulating the disordered sleep-wake cycle and biological rhythm, and relevant basic and clinical researches indicate that the melatonin receptor agonists have good application prospects in the fields of ICU severe diseases and delirium diseases after cancer operation. There is a significant unmet clinical need in the special medical setting of ICU severe, cancer postoperative delirium: 1. there is currently no worldwide approved therapeutic drug for ICU severe and postoperative delirium of cancer. 2. The clinic treatment at home and abroad mainly adopts drugs such as anesthesia, sedative hypnotic drugs, antipsychotic drugs and the like for super-indication, has uncertain effectiveness, multiple and serious adverse reactions and has great potential safety hazard. 3. Oral administration of melatonin receptor agonists for the treatment of delirium is subject to large individual differences, resulting in significant clinical inadequacies. 4. For patients with dysphagia, unconsciousness, or fasting due to therapeutic needs, the oral route of administration is not practical, resulting in a treatment gap. Based on the above limitations, the development of therapeutic drugs for ICU severe cases, cancer postoperative delirium, is an important direction in drug development. Among them, the preparation of melatonin receptor agonists into injections for intravenous administration is a promising technological route. None of the prior art discloses the use of melatonin receptor agonists as injectables for the prevention or treatment of ICU severe and postoperative delirium in cancer. Therefore, the development of the product can fill the technical and product blank in the field, and has important clinical significance and commercial value. Disclosure of Invention Aiming at the current clinical treatment blank and deficiency of ICU severe symptoms and delirium after cancer operation, the invention aims to provide a complete technical solution. In order to achieve the above purpose, the invention adopts the following technical scheme: In a first aspect, the present invention provides an injection. The injection comprises the following components in percentage by weight: Active pharmaceutical ingredient comprising 0.001% to 0.5% of melatonin receptor agonist, which is the basis for therapeutic action. The oil phase carrier contains 5.0 to 30.0 percent of oil for injection, and the oil phase is used as a dissolution carrier of medicines, and the type and the proportion of the oil