US3928609A - Non-alcoholic theophylline product - Google Patents

Non-alcoholic theophylline product Download PDF

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Publication number
US3928609A
US3928609A US348076A US34807673A US3928609A US 3928609 A US3928609 A US 3928609A US 348076 A US348076 A US 348076A US 34807673 A US34807673 A US 34807673A US 3928609 A US3928609 A US 3928609A
Authority
US
United States
Prior art keywords
theophylline
vehicle
alcoholic
pharmaceutical composition
propylene glycol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US348076A
Other languages
English (en)
Inventor
George D Behrakis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dooner Laboratories Inc
Original Assignee
Dooner Laboratories Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dooner Laboratories Inc filed Critical Dooner Laboratories Inc
Priority to US348076A priority Critical patent/US3928609A/en
Priority to CA195,262A priority patent/CA1029657A/fr
Priority to AU66941/74A priority patent/AU474309B2/en
Priority to DE2416216A priority patent/DE2416216C2/de
Priority to ZA00742156A priority patent/ZA742156B/xx
Priority to FR7412199A priority patent/FR2224160A1/fr
Priority to GB1522874A priority patent/GB1453234A/en
Priority to JP3807474A priority patent/JPS5427881B2/ja
Application granted granted Critical
Publication of US3928609A publication Critical patent/US3928609A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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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)
US348076A 1973-04-05 1973-04-05 Non-alcoholic theophylline product Expired - Lifetime US3928609A (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
US348076A US3928609A (en) 1973-04-05 1973-04-05 Non-alcoholic theophylline product
CA195,262A CA1029657A (fr) 1973-04-05 1974-03-18 Theophylline liquide
AU66941/74A AU474309B2 (en) 1973-04-05 1974-03-21 Nonalcoholic theophylline product
DE2416216A DE2416216C2 (de) 1973-04-05 1974-04-03 Oral verabreichbares pharmazeutisches Gemisch
ZA00742156A ZA742156B (en) 1973-04-05 1974-04-04 Improvements in or relating to vehicles for pharmaceutical compositions
FR7412199A FR2224160A1 (fr) 1973-04-05 1974-04-05
GB1522874A GB1453234A (en) 1973-04-05 1974-04-05 Liquid vehicle for pharmaceutical compositions
JP3807474A JPS5427881B2 (fr) 1973-04-05 1974-04-05

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US348076A US3928609A (en) 1973-04-05 1973-04-05 Non-alcoholic theophylline product

Publications (1)

Publication Number Publication Date
US3928609A true US3928609A (en) 1975-12-23

Family

ID=23366547

Family Applications (1)

Application Number Title Priority Date Filing Date
US348076A Expired - Lifetime US3928609A (en) 1973-04-05 1973-04-05 Non-alcoholic theophylline product

Country Status (8)

Country Link
US (1) US3928609A (fr)
JP (1) JPS5427881B2 (fr)
AU (1) AU474309B2 (fr)
CA (1) CA1029657A (fr)
DE (1) DE2416216C2 (fr)
FR (1) FR2224160A1 (fr)
GB (1) GB1453234A (fr)
ZA (1) ZA742156B (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4117132A (en) * 1976-04-02 1978-09-26 Dr. Adolf Seebach Ag Process for the production of stabilized pure theophylline in neutral, aqueous solution
US4364922A (en) * 1980-10-14 1982-12-21 University Of Virginia Alumni Patents Foundation Adenosine antagonists in the treatment and diagnosis of A-V node conduction disturbances
US4708957A (en) * 1984-08-29 1987-11-24 Schering Aktiengesellschaft Injection solution
US5077296A (en) * 1987-12-03 1991-12-31 Hyal Pharmaceutical Corporation Method for treating equine navicular disease with pentoxifylline, and composition containing pentoxifylline for administrating to horses
US5409619A (en) * 1993-08-23 1995-04-25 Reckitt & Colman Inc. Ironing aid composition

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2531337A1 (fr) * 1982-08-04 1984-02-10 Hoechst Lab Nouvelles formes galeniques administrables par voie orale, des derives de la dimethylxanthine solubles
ZA853488B (en) * 1984-05-10 1986-12-30 American Home Prod Transdermal dosage form
GB2551971B (en) * 2016-06-29 2020-09-16 Syri Ltd Taste masked liquid pharmaceutical composition of mebeverine or pharmaceutically acceptable salts thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3109773A (en) * 1961-10-25 1963-11-05 Mead Johnson & Co Bronchodilator expectorant composition containing theophylline and a guaiacol
US3134720A (en) * 1962-06-27 1964-05-26 Bristol Myers Co Medicated gels
US3309271A (en) * 1963-08-30 1967-03-14 Manuf Prod Pharma Methods and composition for inducing choleresis
US3467754A (en) * 1966-08-10 1969-09-16 Mead Johnson & Co Bronchodilator expectorant elixir
US3728346A (en) * 1971-07-16 1973-04-17 Degussa Hydroxyphenylhydroxyalkylaminoalkyltheophyllines

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3109773A (en) * 1961-10-25 1963-11-05 Mead Johnson & Co Bronchodilator expectorant composition containing theophylline and a guaiacol
US3134720A (en) * 1962-06-27 1964-05-26 Bristol Myers Co Medicated gels
US3309271A (en) * 1963-08-30 1967-03-14 Manuf Prod Pharma Methods and composition for inducing choleresis
US3467754A (en) * 1966-08-10 1969-09-16 Mead Johnson & Co Bronchodilator expectorant elixir
US3728346A (en) * 1971-07-16 1973-04-17 Degussa Hydroxyphenylhydroxyalkylaminoalkyltheophyllines

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4117132A (en) * 1976-04-02 1978-09-26 Dr. Adolf Seebach Ag Process for the production of stabilized pure theophylline in neutral, aqueous solution
US4364922A (en) * 1980-10-14 1982-12-21 University Of Virginia Alumni Patents Foundation Adenosine antagonists in the treatment and diagnosis of A-V node conduction disturbances
US4708957A (en) * 1984-08-29 1987-11-24 Schering Aktiengesellschaft Injection solution
AU588242B2 (en) * 1984-08-29 1989-09-14 Asche Aktiengesellschaft Injection solution
US5077296A (en) * 1987-12-03 1991-12-31 Hyal Pharmaceutical Corporation Method for treating equine navicular disease with pentoxifylline, and composition containing pentoxifylline for administrating to horses
US5409619A (en) * 1993-08-23 1995-04-25 Reckitt & Colman Inc. Ironing aid composition

Also Published As

Publication number Publication date
ZA742156B (en) 1975-04-30
AU6694174A (en) 1975-09-25
AU474309B2 (en) 1976-07-15
FR2224160A1 (fr) 1974-10-31
DE2416216C2 (de) 1984-10-31
GB1453234A (en) 1976-10-20
JPS505522A (fr) 1975-01-21
CA1029657A (fr) 1978-04-18
JPS5427881B2 (fr) 1979-09-12
DE2416216A1 (de) 1974-10-24

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