Extended release analgesic for pain control

#This invention relates to extended release analgesic for pain control.

#Analgesics are used to control pain in various situations such as post surgical, post injury, cancer treatment, AIDS treatment and more. Analgesics used include steroidal, non-steroidal, opioid, and non-opioid analgesics. Many of these drugs have very short residence times in the body, ranging from 6 to 12 hours for steroids and non-steroids, to as low as 1 to 3 hours for opioids. Pain from the procedures described can last several days. These analgesics thus must be administered many times in order to be effective in controlling pain.

#There are several methods for extending the time over which analgesics are effective. One is advanced chemical entities. Whereas analgesics such as morphine have a mean residence time of only a few hours, advanced synthetic analgesics such as OxyContin® have an effective residence time in the body of 8 hours. Some drawbacks to this material are the fact that it is orally delivered, and as a result the unit dose may be improperly modified by a patient, resulting in a dangerous overdose, or the patient may not be capable of swallowing the medication.

#Other objects, features and advantages will occur to those skilled in the art from the following description of the preferred embodiments, and the accompanying drawings, in which:

#FIG. 1 is a graph of blood morphine concentrations over time resulting from the injection of aqueous morphine sulfate, and several extended release compounds of the invention;

#FIG. 2 is a graph of blood morphine concentrations resulting from the injection of aqueous morphine sulfate, and two different extended release compounds of the invention using different amounts of calcium as the counter-ion; and

#The following is a description of the preferred embodiment of the invention. The preferred polymer is hyaluronic acid having an average molecular weight of over 1 million Daltons. Purified sterile polymer that is pyrogen free is placed in a clean environment (class 100 or cleaner). The amount of analgesic required for the duration of treatment is weighed out and dissolved in sterile saline for injection. The solution is then sterile filtered since the analgesic powder was not sterile. The polymer is then added and the material is mixed for 24 hours, or until all polymer is dissolved. All beakers, stirbars and instruments were sterilized via autoclaving prior to product contact.

#In the following examples, four prototypes were tested to determine the release rates for the various conditions explained. These prototypes were formulated as follows:

#Sodium hyaluronate with morphine: All work was performed in a class 100 clean hood. 54 mg of morphine hexahydrate was placed in a depyrogenated beaker. 3 ml of sterile saline (0.9% NaCl) was added to the morphine and swirled until it was dissolved. The solution was then drawn up into a syringe. The syringe was fitted with a sterilizing filter, and the solution was passed through the filter into a clean sterile beaker. 45 mg of sterile and pyrogen free hyaluronic acid was weighed, and placed in the beaker with the solution. The hyaluronic acid had a molecular weight in excess of 1 million Daltons. A sterilized stir-bar was placed in the beaker, and the solution was stirred for 24 hours. The solution was then placed in syringes (1 ml per syringe) and stored for subsequent animal tests.