Classifications

• • C—CHEMISTRY; METALLURGY
  • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
  • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
  • C09K3/00—Materials not provided for elsewhere
  • C09K3/30—Materials not provided for elsewhere for aerosols
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/10—Dispersions; Emulsions
  • A61K9/12—Aerosols; Foams

Definitions

• This invention relates to an aerosol anesthetic preparation. More particularly, this invention is concerned with a liquid anesthetic preparation in an aerosol container for topical application which is characterized by resistance to low temperatures.
• the prepartion is designed for relief of surface pain and itching, and provides soothing temporary relief of minor burns, sunburn, cuts, scratches, nonpoisonous insect bites, poison ivy, and minor skin irritations. It may also be used for post-partum care.
• the preparation is nonstinging and nonchilling even when applied to open cuts and wounds.
• the solution of the benzocaine in the polyethylene glycol ester contains at least 10% by weight of benzocaine.
• the liquified propellant is miscible with the polyethylene glycol solvent solution, and the preparation preferably consists of a substantially single phase system, although the benzocaine is not appreciably soluble in the propellant.
• a high proportion of the propellant, particularly the high proportion of the dichlorodifluoromethane, makes it difficult to maintain the desired concentration of benzocaine in solution, especially at temperatures below ordinary room temperature, as may be encountered in the storage, shipping, or use of such preparations.
• This invention is based on the discovery that nonstinging, nonchilling aerosol anesthetic preparations can be prepared While at the same time providing preparations which are single phase systems and which are temperature resistant, being easily reconstitutatable and/or adapted for use at low temperatures.
• the alkyl chain length in the ester groups is critical for achieving these objectives, when the preparation utilizes the propellant mixture described in Serial No. 380,945 and a high concentration of benzocaine.
• Fatty acids derived from coconut oil are normally regarded as having relatively short alkyl groups, as compared with the fatty acids derived from other naturally occurring fats and oils.
• coconut oil For example, a typical analysis of coconut oil shows that it contains from 60 to 65% of fatty acids (principally lauric acid) having chain lengths of C to C and from 35 to 40% of fatty acids (principally myristic acid) having chain lengths of from C to C Nevertheless, during the experimental Work leading to the present invention, it was found that polyethylene glycol diesters formed from mixed coconut oil fatty acids, such as the diester of nonaethylene glycol, failed to produce preparations which could be packed and distributed as essentially single phase systems.
• fatty acids principally lauric acid
• fatty acids principally myristic acid
• the solvent should be formed of diesters wherein the alkyl groups are composed substantially entirely of C to C chain lengths.
• the polyethylene glycol ester solvent for the benzocaine should contain at least by weight of compounds represented by the formula 0 0 II I! R '(J O(CHZCH20)D C RI wherein n is an integer from 7 to 15 and R and R are alkyls containing from 7 to 11 carbons.
• the solvent is composed substantially entirely to of compounds falling within the above formula.
• the polyethylene glycol portion of the solvent molecule can be conveniently provided by starting with compounds such as Polyethylene Glycol 400 (or Carbowax 400) which are composed predominantly of nonaethylene glycol. As indicated, the number of ethylene glycol groups in the compound may vary from 7 to 15. Optimally from 8 to 10 ethylene glycol groups are present.
• a mixed polyethylene glycol can be used where the predominate or average chain lengths correspond with the ranges set out.
• Such polyethylene glycol compounds can be esterified with C to C fatty acids or with mixtures thereof including specifically caprylic, pelargonic, capric, undecanoic, and lauric acids. Specific preferred compounds are polyethylene glycol dicaprylate, dipelargonate, dicaprate, and dilaurate. Other suitable compounds include the caprate caprylate, the laurate caprylate, the caprylate pelargonate, the laurate pelargonate, the laurate caprate, and the caprate pelargonate.
• the propellant consist of at least 70% (viz. from 70 to 100%) by weight of dichlorodifluoromethane. From to 30% of trichlorofluoromethane based on the total weight of the propellant can also be included.
• the utilization of a propellant containing at least 80% (viz. from 80 to 100%) by weight of dichlorodifluoromethane and from 0 to 20% of trichlorofluoromethane is preferred.
• an optimum formulation comprises 80 to 95% dichlorodifiuoromethane in admixture with to 20% trichlorofluoromethane.
• propellant per part of the solvent.
• at least 1.5 parts of the propellant are employed per part of solvent.
• for each part of solvent from 1.5 to 2.5 parts of propellant can be used.
• the solvent solution (excluding the propellant) should contain at least by weight of benzocaine. It will be understood that this is based on the combined weight of the benzocaine and solvent. In certain preferred embodiments, at least by weight of benzocaine is present in the solvent solution.
• the benzocaine concentration can range up to about 22%. It will be understood of course that the benzocaine can only be employed up to its saturation solubility in the solvent solution, or in the mixture of the solvent solution with the propellant.
• Example 1 A single phase, temperature resistant aerosol topical anesthetic is prepared according to the following formulation:
• Formulation A Wt. percent Nonaethylene glycol (Polyethylene Glycol
• the benzocaine is dissoived in the nonaethylene glycol .dilaurate at room temperature (e.g. 70 F.).
• the solvent solution is then introduced into the aerosol containers in a manner well known in the art.
• the propellant is introduced as a premixed liquid.
• the containers are then shaken to form a single liquid phase.
• the preparation is easily reconstitutable if a multiple phase system results from temperature reduction or after the preparation is solidified by freezing.
• auxiliary agents may be incorporated in the formula, such as oil-soluble antiseptics like benzethonium chloride, oxyquinoline, oxyquinolinebenzoate, hexachlorophene, etc.
• Example 2 Another aerosol preparation is produced as described in Example 1, except that the following formulation is used:
• Formulation B Wt. percent Nonaethylene glycol (Polyethylene Glycol 400) caprate caprylate 28.9 Benzocaine 5.8 Dichlorodifiuoromethane 55.4 Trichlorofiuoromethane 9.9
• the preparation of Formulation B is particularly useful under relatively cold conditions.
• the product remains as a single liquid phase in the container down to temperatures as low as 0 F.
• Example 3 Additional preparations can be prepared by procedures similar to that used for the preparation of Examples 1 and 2, but utilizing one of the following formulations:
• Formulation C Wt. percent Nonaethylene glycol (Polyethylene Glycol While in the foregoing specification this invention has been described in relation to certain preferred embodiments thereof, and many details have been set forth for purposes of illustration, it will be apparent to those skilled in the art that the invention is susceptible to other embodiments and that many of the details described herein can be varied considerably without departing from the basic principles of the invention.
• a liquid anesthetic preparation in an aerosol container said reparation consisting essentially of a single phase mixture of a liquefied chlorofiuoroalkane propellant and a solution of benzocaine in a polyethylene glycol diester solvent
• said propellant being selected from the group consisting of dichlorodifiuoromethane, and mixtures of dichlorodifluoromethane with trichlorofiuoromethane, at least 1.5 parts by weight of said propellant being employed per part of said solvent, said propellant containing at least 70% by weight of dichlorodilluoromethane, said solution of said benzocaine in said solvent containing at least 10% benzocaine by Weight
• said solvent consisting essentially of polyethylene glycol diesters at least by weight of which diesters are represented by the formula wherein n is an integer from 7 to 15 and R and R are alkyls containing from 7 to 11 carbons.
• diesters represented by said formula are nonaethylene glycol diesters having ester groups selected from the group consisting of dilaurate, caprate caprylate, dicaprate, dipelargonate, and mixtures of said diesters.
• diesters represented by said formula are nonaethylene glycol diesters having ester groups selected from the group consisting of dilaurate, caprate caprylate, dicaprate, dipelargonate, and mixtures of said diesters.
• a liquid anesthetic preparation in an aerosol container consisting essentially of a single phase mixture of a liquefied chlorofluoroalkane propellant and a solution of benzocaine in a polyethylene glycol diester solvent, said propellant being a mixture of dichlorodifluoromethane with trichlorofluoromethane and containing at least 70% by weight of said dichlorodifluoromethane, from 1.5 to 2.5 parts by weight of said propellant being employed per part of said solvent, said solution of said benzocaine in said solvent containing at least by weight of benzocaine, said solvent consisting essentially of polyethylene glycol diesters at least 90% by Weight of which diesters are represented by the formula:
• n is an integer from 7 to and R and R are alkyls containing from 7 to 11 carbons.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Dispersion Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Materials Engineering (AREA)
• Dermatology (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Medicinal Preparation (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Priority Applications (5)

Applications Claiming Priority (2)

Publications (1)

Family

ID=27009179

Family Applications (1)

Country Status (4)

Cited By (6)

Citations (3)

• 1964
  • 1964-10-01 US US400949A patent/US3322624A/en not_active Expired - Lifetime
• 1967
  • 1967-01-18 GB GB2713/67A patent/GB1122153A/en not_active Expired
  • 1967-05-29 CH CH754567A patent/CH478083A/de not_active IP Right Cessation
  • 1967-05-30 DE DE19671617292 patent/DE1617292A1/de active Pending

Patent Citations (3)

Also Published As

Similar Documents