# US 5,346,903 A · Aqueous suspension preparation for injection, method for producing the same and use thereof for producing pain relief > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,346,903 A - Document ID: US5346903A - Status: Granted - Kind: A - Application number: 07/979,128 - Filed: 1992-11-20 - Granted: 1994-09-13 - Earliest claimed: 1990-03-20 - Assignees: Stichting Catharina Ziekenhuis - Inventors: Eric W. Ackerman; Rene J. E. Grouls; Hendrikus H. M. Korsten - Web page: https://patentgrep.com/patent/US5346903A ## CPC - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 31/245: Amino benzoic acid types, e.g. procaine, novocaine (salicylic acid esters A61K31/60) - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61P 23/02: Local anaesthetics - A61P 25/02: for peripheral neuropathies - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to an aqueous suspension preparation for injection and to a method for producing the same and further relates to the use of said preparation for producing pain relief. The invention particularly relates to a preparation as indicated hereinabove, comprising a water-insoluble local anesthetic and/or narcotic analgesic suspended in an aqeuous medium, which preparation can be succesfully used for epidural and intrathecal pain relief and for conduction anesthesia and infiltration anesthesia. The preparation is stabilized by the addition of a non-ionic surface-active agent in an amount of less than 1 wt. %. The particles of the water-insoluble active agent have a mean particle diameter of less than 20 .mu.m. More than 99% of the particles have a diameter of less than 100 .mu.m and more than 90% have a diameter of less than 50 .mu.m. ## Claims ### Claim 1 An aqueous suspension preparation for injection to combat pain comprising a water-insoluble local anesthetic and/or narcotic analgesic in the form of particles wherein more than 99% of said particles have a diameter of less than 100 .mu.m and more than 90% have a diameter of less than 50 .mu.m, the mean particle diameter being less than 20 .mu.m, said particles being suspended in an aqueous medium wherein the sole agent for stabilizing the suspension is a non-ionic surface-active agent in an amount of less than 1 wt. %. ### Claim 2 (depends on 1) The preparation according to claim 1, wherein said local anesthetic and/or narcotic analgesic is or are present in an amount of from 1 to 15 wt. %. ### Claim 3 (depends on 1) The preparation according to claim 1, wherein said local anesthetic is of the ester-type or of the amide type, or a water-insoluble salt thereof. ### Claim 4 (depends on 3) The preparation according to claim 3, wherein said local anesthetics is a lower alkyl ester of p-aminobenzoic acid. ### Claim 5 (depends on 4) The preparation according to claim 4, wherein said local anesthetic is the n-butylester of p-aminobenzoic acid. ### Claim 6 (depends on 1) The preparation according to claim 1, wherein said narcotic analgesic is a natural or (semi-) synthetic opioid or a water-insoluble salt thereof. ### Claim 7 (depends on 1) The preparation according to claim 1, wherein said non-ionic surface-active agent comprises a polyoxyalkylene ether of a polyhydroxy alcohol which is partially esterified with a higher fatty acid. ### Claim 8 (depends on 7) The preparation according to claim 7, wherein said non-ionic surface-active agent comprises a polysorbate. ### Claim 9 (depends on 8) The preparation according to claim 8, wherein said non-ionic surface-active agent comprises polysorbate 80. ### Claim 10 (depends on 1) The preparation according to claim 1, wherein said non-ionic surface-active agent is present in an amount of less than 0.4 wt. %. ### Claim 11 (depends on 10) The preparation according to claim 10, wherein said non-ionic surface-active agent is present in an amount in the range of from 0.01 to 0.2 wt. %. ### Claim 12 (depends on 1) The preparation according to claim 1, comprising a mixture of a water-insoluble local anesthetic and narcotic analgesic in a weight ratio from 10:1 to 1:10. ### Claim 13 (depends on 1) The preparation according to claim 1, wherein said aqueous medium is a physiological salt solution or a diluted glucose solution. ### Claim 14 A process for producing an aqueous suspension preparation for injection to combat pain comprising a water-insoluble local anesthetic and/or narcotic analgesic in the form of particles wherein more than 99% of said particles have a diameter of less than 100 .mu.m and more than 90% have a diameter of less than 50 .mu.m, the mean particle diameter being less than 20 .mu.m, said particles being suspended in an aqueous medium wherein the sole agent for stabilizing the suspension is a non-ionic surface-active agent in an amount of less than 1 wt. %, said process comprising: suspending the water-insoluble local anesthetic in powder form in the aqueous medium containing the non-ionic surface-active agent to form a suspension; sterilizing the suspension thus obtained at about 120 deg. C. for about 20 minutes to form a wholly liquid mixture; cooling the wholly liquid mixture to room temperature while vigorously stirring or shaking said liquid mixture; then freezing the cooled liquid mixture at a temperature between 0 deg. C. and -25 deg. C. to form a frozen mixture; and defrosting the frozen mixture while vigorously shaking the frozen mixture. ### Claim 15 (depends on 14) The process according to claim 14, wherein the freeze-defrost cycle is repeated once or twice while the mixture is vigorously shaken during the defrost period. ### Claim 16 A method for epidurally treating pain in patients in need for pain relief, comprising administering epidurally to said patient an aqueous suspension preparation for injection to combat pain comprising a water-insoluble local anesthetic and/or narcotic analgesic: in the form of particles wherein more than 99% of said particles have a diameter of less than 100 .mu.m and more than 90% have a diameter of less than 50 .mu.m, the mean particle diameter being less than 20 .mu.m, said particles being suspended in an aqueous medium wherein the sole agent for stabilizing the suspension is a non-ionic surface-active agent in an amount of less than 1 wt. %.