Study On Dihydroetorphine Hydrochloride Nasal Spray

As a powerful opium analgesic drug, DHE made its first appearance in the 1980s before being synthesized by AMMS. During its initial screening it was 12000 times as effective as morphine. It was clinically used mainly for acute pain in the late stage of cancer. Because of its strong first-pass effect and its property as a micro drug, DHE was ineffective orally and was mainly used as sublingual tablets. Not only does injection require specific conditions of patients who are chronic users of analgesic , but causes suffering to patients due to injection. Therefore, daily administration was undesirable .On the other hand, While oral tablets are easy to use, they can' t be conveniently applied to critically ill patients and coma patients.A nasal spray was developed to maximize the instant effect and strong analgesic properties on the basis of its physical, chemical and pharmaceutical properties. Alteration of the administration route can accelerate its effect and prevent the first-pass effect, Leading to improved biological utilization and facilitating its administration to victims of pain for whom oral use or injection is difficult under clinical or wartime conditions.This study started by screening prescriptions of DHE nasal spray. Adequate solutions and pH were selected by studying the physical and chemical properties and stability of raw materials. The ideal pH was4.0 and water was found to be the best solution. To enhance the absorption of the drug by mucous membrane of nose.The result suggested the way that 1%D was added had effect on improvement of osmosing drug.This study established the method of measurement of the content of DHE in nasal spray. The findings of Methodological studies suggested that the content of solution was determined using UV spectrophotography and content of each press was determined using HPLC methods, both of which were reasonably accurate and precise. Preparation-related substances could be determined by means of self-contrast of the main components, which was a highly sensitive and specific method, without any interference with the main components from the degradation product .Experiments of acceleration of three months showed that each value was up to the standard, pointing to the good physical and chemical stability.To inspect the local toxicity of nasal spray, tests on lagophthalmos, cilium of hoptoad superior jaw and nasal cilium of big rats were employed. The markers were measured repectly by eyes, light microscope and scanning eletron microscope. The result shows that al 1 of these methods can be used to evaluate the toxicity on mucous membrane. They all have merits and defects .DHE nasal spray was approved.to have no obvious toxicity.The dosage of DHE to adminstrated is very small. From the literature, contentration in blood that can be detected is only several ng mL-1. Considered the confines of instrument, evaluating the analgesic effect with pharmacodynamics .By determining painthreshold at different dosages and administration routes .The study protracted the content effect curves and calculated the ED95 and equivalent doses. The time-effect curves were protracted according to the data. The result suggests that DHE is adminstrated by nasal could be effctive in short time , the speed that it produces analgesic effect is the biggest contrast to administration by subcutaneous and sublingual. The dosages for small rats to administrated by subcutaneous, nasal and sublingual routes respectively were1. 3ug kg-1, 2. 0ug kg-1 and 3. 0ug kg-1. The dosages for big rats were2.0ug kg-1. 3.0ug kg-1 and 5.0ug kg-1.By studying the nasal spray of DHE pharmacologically, this paper shows that this spray was stable in physical and chemical properties and controllable in quality. Nasal administration can produce quicker effect than sublingual administration of the same dose, which suggests its better absorption. A smaller dosage of intranasal administration can be as effective as a larger dosage of sublingual administration, which is the evidence that intranasal administ...