Theophylline is a xanthine derivative commonly used for its bronchodilator effects. It is a naturally occurring compound found in tea leaves and cocoa beans and is widely used in the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).

Chemical Composition and Structure

The chemical structure of theophylline is similar to that of caffeine and theobromine. It is composed of a methylxanthine core with the chemical formula C7H8N4O2. The molecular structure includes a fused double-ring system with nitrogen atoms at positions 1 and 3, and methyl groups at positions 1 and 3.

Physical Properties

Theophylline typically appears as a white, crystalline powder that is slightly soluble in water and alcohol. It has a bitter taste and is odorless. The melting point of theophylline is around 270°C.

Production Process

The production of theophylline involves several steps:

• Extraction: Theophylline can be extracted from natural sources such as tea leaves and cocoa beans, although synthetic production is more common.
• Chemical Synthesis: Synthetic production involves the chemical modification of xanthine. The process includes methylation and oxidation steps to produce theophylline.
• Purification: The synthesized theophylline is purified using crystallization or chromatography techniques to ensure a high degree of purity.
• Formulation: The pure theophylline is then formulated into various dosage forms, including tablets, capsules, and solutions for oral or intravenous administration.
• Packaging: The final product is packaged under controlled conditions to ensure stability and purity.

Applications

• Medical: Theophylline is primarily used in the medical field as a bronchodilator. It helps relax the smooth muscles of the airways, making it easier to breathe (1). It is used in the treatment of asthma, COPD, and other respiratory conditions (2).
• Pharmaceutical: Theophylline is included in various pharmaceutical formulations for oral and intravenous administration. It is often used in combination with other medications to enhance its therapeutic effects.

Research: Theophylline is used in research settings to study its pharmacological effects and potential new therapeutic applications.

Environmental and Safety Considerations

Environmental Impact: The production of theophylline has a moderate environmental impact. Waste products from chemical synthesis and purification processes must be managed to minimize environmental contamination.

Safety: Theophylline is generally safe when used as directed. However, it has a narrow therapeutic index, meaning that the difference between a therapeutic dose and a toxic dose is small. It is essential to monitor blood levels of theophylline in patients to avoid toxicity. Side effects can include nausea, vomiting, insomnia, and, in severe cases, cardiac arrhythmias and seizures.

Cosmetics - INCI Functions

Skin conditioning agent - Miscellaneous.  This ingredient has the task of modifying and improving the condition of the skin when it is damaged or dry, reducing flaking and restoring its elasticity.

Molecular Formula  C₇H₈N₄O₂

Molecular Weight    180.16 g/mol

CAS     58-55-9

UNII    C137DTR5RG    0I55128JYK

EC Number  200-385-7

Synonyms:

1,3-Dimethylxanthine

Elixophyllin

References__________________________________________________________________________

(1) Scurek M, Brat K. A narrative review of theophylline: is there still a place for an old friend? J Thorac Dis. 2024 May 31;16(5):3450-3460. doi: 10.21037/jtd-23-1781. Epub 2024 May 29. PMID: 38883616; PMCID: PMC11170423.

(2) Park SJ, Hahn HJ, Oh SR, Lee HJ. Theophylline Attenuates BLM-Induced Pulmonary Fibrosis by Inhibiting Th17 Differentiation. Int J Mol Sci. 2023 Jan 5;24(2):1019. doi: 10.3390/ijms24021019.

Abstract. Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there are two approved drugs for IPF, they were not able to completely cure the disease. Therefore, the development of new drugs is required for the effective treatment of IPF. In this study, we investigated the effect of theophylline, which has long been used for the treatment of asthma, on pulmonary fibrosis. The administration of theophylline attenuated the fibrotic changes of lung tissues and improved mechanical pulmonary functions in bleomycin (BLM)-induced pulmonary fibrosis. Theophylline treatment suppressed IL-17 production through inhibiting cytokines controlling Th17 differentiation; TGF-β, IL-6, IL-1β, and IL-23. The inhibition of IL-6 and IL-1β by theophylline is mediated by suppressing BLM-induced ROS production and NF-κB activation in epithelial cells. We further demonstrated that theophylline inhibited TGF-β-induced epithelial-to-mesenchymal transition in epithelial cells through suppressing the phosphorylation of Smad2/3 and AKT. The inhibitory effects of theophylline on the phosphorylation of Smad2/3 and AKT were recapitulated in BLM-treated lung tissues. Taken together, these results demonstrated that theophylline prevents pulmonary fibrosis by inhibiting Th17 differentiation and TGF-β signaling.

Poe RH, Utell MJ. Theophylline in asthma and COPD: changing perspectives and controversies. Geriatrics. 1991 Apr;46(4):55-6, 61-5. PMID: 2010095.

Abstract. Theophylline's role in the treatment of airway obstruction has been challenged, yet it remains a useful agent in the management of obstructive lung disease. It has a narrow therapeutic range and frequent side effects. Drug interactions are common, and variations in theophylline clearance among patients arise from individual differences in its absorption, metabolism, and elimination. Acute bronchospasm is best treated with inhaled sympathomimetic agents, but the nonbronchodilator effects of theophylline offer therapeutic benefits for the patient with non-reversible disease. When properly monitored by serum level determinations, theophylline may be used as an adjunct to aerosol therapy and corticosteroids in asthma. However, the patient with COPD may benefit the most from an empiric trial of the drug, using lower doses than were commonly employed in the past.

Scholle S. Theophylline in the treatment of sleep-related breathing disorders. Z Arztl Fortbild Qualitatssich. 2001 Jan;95(1):35-8. German. PMID: 11233493.

Abstract. The methylxanthine derivates are known to have respiratory stimulant properties. Therefore theophylline is used in sleep related disturbances of breathing. Theophylline reduces central apneas and periodic breathing in infants. The efficiency of theophyllin is confirmed in reducing central apneas in patients with neurologic diseases or Cheyne Stokes breathing in patients with congestive heart failure. In patients with obstructive sleep apnoea the effect of theophylline is doubtful. An effect of therapy exists in some mild forms of sleep apnoea (apnoea index < 20/h total sleep time). Further studies are necessary to investigate the precise mechanism of of theophylline in obstructive sleep apnoea.