Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/16—Amides, e.g. hydroxamic acids
  • A61K31/18—Sulfonamides

Definitions

• This invention relates to antibacterial compositions and to methods of treatment with said compositions.
• Burn wound infection and septicemia refractory to topical and systemic antibiotic therapy are the chief causes of death in severely burned patients, the major pathogen in many instances being Pseuaomonas aeruginosa.
• Parenteral antibiotics are only partially effective in the majority of cases, probably because the devascularized tissue in the area of the burn is not reached by the antibiotic. Therefore, effective topical medication which penetrates the devascularized area and burn surface is needed to suppress bacterial growth substantially.
• the hydrochloride of p-aminomethylbenzenesulfonamide has been used with some success for the treatment of burns.
• the use of this compound undesirably produces a change in the acid-base balance of the patient and, specifically, it reduces significantly the carbon dioxide combining power of the blood.
• Significant changes in the acid-base balance cause hyperventilation as the body seeks to compensate for the imbalance, and this can be especially hazardous to patients with impaired renal or pulmonary function.
• the instant invention resides in the concept of a new composition of matter which is a therapeutic preparation adapted to be topically applied as a protective antibacterial mantle in the treatment of burn wounds of humans which comprises a pharmaceutically-acceptable hydrophilic base having incorporated therein in antibacterially effective amount a water-soluble salt of paminomethylbenzenesulfonamide with a rapidly-metabolizable and pharmaceutically-acceptable organic acid.
• this invention resides in the concept of ice a new method of treating burn wounds of humans which comprises applying topically to the burned area as a protective antibacterial mantle my new therapeutic preparation.
• the water-soluble salt of p-aminomethylbenzenesulfonamide used in the practice of this invention is incorporated into my new therapeutic compositions in antibacterially effective amount; for the purposes of this invention the amount of the salt is approximately 5-20 percent by weight of the composition, 7-15 percent ordinarily being the preferred range.
• the mixing and blending procedures conventional in the pharmaceutical art can be employed to distribute the p-aminornethylbenzenesulfonamide salt uniformly throughout the hydrophilic base.
• the new therapeutic composition afforded by the present invention is highly effective in suppressing bacterial growth in burn wounds of humans and moreover it has the very important advantage that it can be used in relatively large quantity in the treatment of large and severe burns with minimal effect on the acid-base balance of the patient, so that little or no acidosis is produced, nor is any other major untoward response produced.
• the p-aminomethylbenzenesulfonamide salts useful in the practice of this invention are generally speaking the water-soluble salts obtained by interaction of p-aminomethylbenzenesulfonamide with a suitable pharmaceutically-acceptable organic acid, the anion of which is susceptible to rapid metabolism when absorbed through the human skin into the blood stream.
• the acids of this type which are well-known, are illustrated by, but not limited to, acetic acid, propion-ic acid, citric acid, isocitric acid, cis-aconitic acid, succinic acid, fuman'c acid, malic acid, and glutamic acid.
• the preferred salts of the above-indicated type are those which yield aqueous solutions with pH in the approximate range 6.07.0.
• p-Aminomethylbenzenesulfonamide acetate is the preferred salt species.
• the therapeutically-acceptable hydrophilic vase used in formulating the antibacterial preparations of this invention is a Well-known and conventional class in the pharmaceutical art.
• emusion bases sometimes referred to as water removable ointment bases, which consist of an aqueous phase, one or more emulsifying agents, and an oleaginous phase.
• the aqueous phase usually forms 10-80 percent of the total base, and additional water can be incorporated if desired.
• a humectant for example glycerol, propylene glycol, or a polyethylene glycol, is generally included in the aqueous phase.
• the oleaginous phase generally includes one or more Waxes, petrolatum, mineral oils, fats, and higher aliphatic alcohols, and the like.
• the emulsifiers are soaps, polyglycol esters, quaternary ammonium compounds, alkyl sulfates, alkyl aryl sulfonates, and the like.
• Antioxidants and preservative agents may be also added to the hydrophilic base to improve stability and shelf life.
• the new preparations of this invention can be obtained in the form of semi-solid or paste-like ointments and creams for topical application by spreading, smearing, spraying, or the like, on the area to be treated.
• my new therapeutic preparations can be formulated to include a suitable propellant for application from a pressurized container in the form of an aerosol.
• Treatment should be started as soon as the patients burn is debrided, cleaned, and evaluated.
• My new thera Treatment is applied in amount and in frequency sufficient to provide and maintain a complete mantle for the burn wound, a layer about one-sixteenth of an inch thick applied twice daily being generally satisfactory.
• Dressings are ordinarily not applied, and if used should be coarse and loose.
• the burn surface may be cleaned by hydrotherapy and the therapeutic preparation replaced.
• the duration of application generally ranges from a few days to several weeks depending on the severity of the burn, the degree of infection, and the rate of healing. Since there are no significant electrolyte changes produced, there is no necessity for close monitoring of electrolytes during the course of treatment.
• second and third degree burns covering 30-40 percent of the body area of a 70 kg. patient, it is usually satisfactory to use approximately one-half pound per application, that is, a total of one pound per day, when there is applied a one-sixteenth inch layer of a pherapeutic preparation containing 10-12 percent of the p aminomethylbenzenesulfonamide salt, for instance the acetate.
• a pherapeutic preparation containing 10-12 percent of the p aminomethylbenzenesulfonamide salt, for instance the acetate.
• the amount of the therapeutic preparation used par day will vary according to the nature and site of the burn; for example, when burns in the gluteal area are involved, the preparation may be accidentally rubbed off and need replacement more often than will usually be the case when an arm burn is involved.
• my new therapeutic preparation is particularly adapted to the treatment of burn wounds, it is also highly effective in the topical antibacterial treatment of open wounds generally, the method of application being similar to that used in treating burns.
• p-Aminomethylbenzenesulfonamide salts The required p-aminomethylbenzenesulfonamide salts are conveniently obtained by interacting appropriate quantities of p-aminomethylbenzenesulfonamide and a suitable weak organic acid in a solvent and then isolating the salt thus produced by conventional means. This procedure is illustrated below.
• This salt was soluble in water at 25 C. to the extent of 20 percent, the pH of the 1 percent aqueous solution being 6.8.
• p-aminomethylbenzenesulfonamide salts are incorporated into pharmaceutically-acceptable hydrophilic vehicles using manipulative techniques well-known in the art. Illustrated below is the preparation of a cream containing p-aminomethylbenzenesulfonamide acetate; hydrophilic creams containing this salt represent preferred embodiments of this invention and have been found especially effective and convenient in the treatment of burn wounds of humans.
• a mixture of 2.7 parts of cetyl alcohol, 9.0 parts of stearyl alcohol, and 9.0 parts of spermaceti is melted and to this melt there are added 0.03 part of n-propyl phydroxybenzoate and 0.25 part of methyl p-hydroxybenzoate.
• Separate aqueous solutions of 2.0 parts of polysorbate (polyoxyethylene 20 sorbitan monooleate) and of 11.6 parts of glycerol are prepared and each is warmed to the same temperature as the first solution, and then the three solutions are mixed and stirred until the resulting mixture has cooled to room temperature.
• the therapeutic preparations provided by this invention have been used in the manner above-indicated in treatment of first, second, and third degree burns covering 3 to 60 percent of the body surface area of humans, and in every instance have afforded safe and effective control of burn wound infection. In no case where death of the patient occurred was septicemia a primary cause of death.
• a therapeutic preparation which comprises a pharmaceutically-acceptable hydrophilic base having incorpo rated therein in antibacterially effective amount a watersoluble salt of p-aminomethylbenzenesulfonamide with a rapidly-metabolizable, pharmaceutically-acceptable organic acid.
• a therapeutic preparation in accordance with claim 1 wherein the water-soluble salt is p-aminomethylbenzenesulfonamide acetate.
• a therapeutic cream which comprises a pharmaceutically-acceptable hydrophilic base having incorporated therein 7-15 percent by weight of p-aminomethylbenzenesulfonamide acetate.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Medicinal Preparation (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=24133821

Family Applications (1)

Country Status (6)

Cited By (2)

Citations (1)

• 1966
  • 1966-03-18 US US535356A patent/US3497599A/en not_active Expired - Lifetime
• 1967
  • 1967-03-06 GB GB10534/67A patent/GB1145193A/en not_active Expired
  • 1967-03-13 IL IL27594A patent/IL27594A/en unknown
  • 1967-03-15 FR FR98829A patent/FR6287M/fr not_active Expired
  • 1967-03-17 BE BE695694D patent/BE695694A/xx unknown
  • 1967-03-17 NL NL6704087A patent/NL6704087A/xx unknown

Patent Citations (1)

Also Published As

Similar Documents