Reservoir type ropivacaine pharmaceutical composition as well as preparation method and application thereof

Abstract

The invention provides a reservoir type ropivacaine pharmaceutical composition as well as a preparation method and application thereof. The pharmaceutical composition comprises: ropivacaine, a pharmaceutical solvent, a medicinal phospholipid, medicinal oil, and pharmaco enhancers, a non-essential antioxidant and a non-essential acid-base regulator. The pharmaceutical composition has a controllable release behavior and a sustained release effect, can significantly reduce the peak serum concentration of the drug, maintain a stable plasma concentration in the body, prolong the effective treatment time, reduce the effective therapeutic dose, improve the utilization of the drug, and reduce the risk of neurotoxicity. The pharmaceutical composition has a long-lasting analgesic effect and can be used for pain treatment.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a storage type ropivacaine pharmaceutical composition, a preparation method thereof, and an application thereof for preparing a medicine for treating postoperative pain. The pharmaceutical composition has controllable release behavior and sustained release effect, can significantly reduce the peak plasma concentration of the drug, maintain a stable blood drug concentration in the body, prolong the effective treatment time, reduce the effective treatment dose, improve the utilization rate of the drug, and reduce neurological stress. Risk of toxicity, long-acting analgesic effect, can be used to treat postoperative pain. Background technique [0002] Postoperative pain is a comprehensive response to soft tissue trauma during hypersensitive surgery that stimulates the central nervous system. Cause various complications, have a strong impact on the postoperative rehabil...

AI Technical Summary

Problems solved by technology

However, the preparation has high viscosity and poor needle passability, which brings inconvenience to clinical use.

At the same time, the effective bioavailability of its drugs is low, which will lead to the waste of drugs

[0010] CN109316602A provides a compound slow-release drug delivery system composed of local anesthetics, non-steroidal anti-inflammatory drugs, solvents and slow-release materials. Although it has a certain slow-release analgesic effect and the function of promoting wound healing, the non-steroidal anti-inflammatory drug Body anti-inflammatory drugs have a capping effect, and have the disadvantages of easily causing gastrointestinal adverse reactions, nervous system and cardiovascular system toxicity

At the same time, the proportion of organic solvents is relatively large, reaching 30-40%, which is easy to cause irritation at the injection site and poses a safety hazard

[0011] CN108743952A provides a kind of phospholipid-miscible solvent-oil as carrier local anesthetic slow release preparation and preparation method, it adopts benzyl benzoate, ethanol and benzyl alcohol as solvent, the total amount of solvent is as high as 40~50%, it is easy to cause injection Partial irritation and systemic adverse reactions, there are potential safety hazards

Similarly, non-steroidal anti-inflammatory drugs have a capping effect and have the disadvantages of easily causing gastrointestinal adverse reactions, nervous system and cardiovascular system toxicity

In addition, the delivery carrier is composed of polyorthoester, polar aprotic solvent and viscosity reducing agent triglyceride, the viscosity of the obtained composition is relatively high, the needle penetration is poor, and the convenience of clinical administration is poor

[0014] In addition, according to the literature Anesth Analg.2006Sep; 103(3):608-14, when nerve fibers are exposed to low concentrations of local anesthetics for a long time, it will lead to a significant delay in the growth of neurites, and the axonal transport of actin Destroyed, causing damage to nerve fibers, producing symptoms such as neuroinflammation or neurofibrosis

[0015] At present, the above-mentioned patent documents all use commonly used excipients in this field. Although the resulting composition has a certain sustained-release effect, it has low drug availability, high irritation at the injection site, large safety hazards, poor needle penetration, and complicated processes. , poor stability and other shortcomings

The composition of the present invention is improved on the basis of existing research techniques, and an appropriate amount of drug effect enhancer is added, which can not only maintain the slow-release effect and good stability of the composition, but also prolong the duration of conventional sustained-release preparations under the same dosage. The duration of the drug effect, and can reduce the effective therapeutic dose under the same analgesic drug effect, improve the motor nerve block situation, and improve the safety of medication, which has not been reported in this field

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