Classifications

• • 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
  • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers

Definitions

• ABSTRACT An improved liquid vehicle for a pharmaceutical composition of a mixture of propylene glycol and glycerine, a novel pharmaceutical composition of theophylline and this vehicle, comprising a composition which serves to solubilize the theophylline without ethyl alcohol, and the process for making the vehicle and the pharmaceutical composition are disclosed.
• compositions which include the type of compounds as the above agent have been used for the treatment in human patients of bronchiospasm, cardiac asthma, and as a diuretic, and in the veterinary field as an asthma remedy and heart mediamlant for animals.
• compositions are administered to humans orally, rectally or parenterally.
• rectal administration may produce local irritation and parenteral administration is often painful and sometimes dangerous, theophylline is commonly taken orally.
• an aqueous mixture of propylene glycol and glycerin have been found to be an effective liquid vehicle for a therapeutically active agent.
• the active ingredient for treatment of bronchial and cardiac asthma in the novel compositions of the invention is theophylline, its salts, complexes or derivatives thereof.
• These compounds include theophylline-ethylenediamine (aminophylline), theocin soluble (theophyllinesodium acetate), oxytocphylline (choline theophyllinate), theophylline-choline and 7-hydroxyethyltheophylline.
• the process according to the invention includes the mixing of a solution of the active agent suspended in glycerin with propylene glycol.
• various sweetening, flavoring, and coloring agents are preferably employed in preparing oral dosage forms of the present type.
• the pharmaceutical composition thus resulting is an oral dosage form of pure theophylline without alcohol which is stable at room temperature.
• the preferred form of theophylline is anhydrous in this composition, although other forms could be used by adjustment to correspond to differing molecular weights.
• the key ingredients in the solubilizing vehicle are propylene glycol (about 20%) and glycerine (about 3 10%). These maintain physical stability in variations of temperature.
• the therapeutically effective dosage level of theophylline was about 2-3 mg./kg. of body weight.
• the individual dosage of the oral theophylline for an adult is about 45cc, or 3 tablespoons, taken three times a day, with an additional 2 tablespoons at night. This may be increased for severe asthmatic attacks up to 5 tablespoons, but is limited for children to about a teaspoonful per pounds of body weight.
• Specific dosage generally varies with body weight, metabolism, and other individual characteristics.
• EXAMPLE The following example shows the ingredients used, methods of preparation, and therapeutic results obtained from the preferred embodiment of the invention.
• the theophylline is separately suspended with gentle agitation in heated glycerine at a temperature of 65-70C (Solution 2).
• Solution 2 is then dissolved in propylene glycol, previously heated to 65-70C, with gentle mixing while maintaining the temperature at 6570C until the resulting mixture becomes completely clear, after which time the mixing is continued for about 10 minutes.
• Solution 2 is then mixed with Solution 1.
• a heated sorbitol solution of about C is added with stirring.
• the mixture is cooled to 38C before adding flavor and bringing to final volume with purified water.
• the resulting syrup is cooled for a day and then filtered through a filter press at 30-40 psi.
• the mixture should have a pH of about 4.5 to maintain stability.
• results obtained The efficacy and acceptability of the preferred embodiment of the present invention has been shown in recent studies. For example, children ranging in ages between 8-12 suffering from asthma wheezing on a day-to-day basis were treated. Pulmonary function tests show improvement in overall condition. Blood serum concentration was also measured. Good blood levels were obtained, i.e., about 5 micrograms/ml. or greater in 15 to 30 minutes, and, in a few cases, in 5 minutes. The blood levels remained for up to 6 hours some as long as 8 hours. A blood concentration of 5 micrograms/ml. of theophylline is generally accepted by the art as a therapeutic concentration.
• a non-alcoholic composition for the treatment of bronchiospasm, cardiac asthma and as a diuretic consisting essentially of an effective amount of anhydrous theophyllin and a pharmaceutically acceptable vehicle consisting essentially of 20% propylene glycol and 10% glycerine and water.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Engineering & Computer Science (AREA)
• General Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Priority Applications (8)

Applications Claiming Priority (1)

Publications (1)

Family

ID=23366547

Family Applications (1)

Country Status (8)

Cited By (5)

Families Citing this family (3)

Citations (5)

• 1973
  • 1973-04-05 US US348076A patent/US3928609A/en not_active Expired - Lifetime
• 1974
  • 1974-03-18 CA CA195,262A patent/CA1029657A/en not_active Expired
  • 1974-03-21 AU AU66941/74A patent/AU474309B2/en not_active Expired
  • 1974-04-03 DE DE2416216A patent/DE2416216C2/de not_active Expired
  • 1974-04-04 ZA ZA00742156A patent/ZA742156B/xx unknown
  • 1974-04-05 JP JP3807474A patent/JPS5427881B2/ja not_active Expired
  • 1974-04-05 GB GB1522874A patent/GB1453234A/en not_active Expired
  • 1974-04-05 FR FR7412199A patent/FR2224160A1/fr not_active Withdrawn

Patent Citations (5)

Also Published As

Similar Documents