Detailed Analysis of the Scope and Claims of United States Patent 4,088,750
Introduction
United States Patent 4,088,750, titled "Method and preparation for increasing bioavailability of digoxin," is a significant innovation in the field of pharmaceuticals, particularly in the administration of the cardiac glycoside digoxin. This patent, issued to Burroughs Wellcome Co., addresses the critical issue of bioavailability in digoxin therapy.
Background of the Invention
Digoxin, a medication used to treat heart conditions such as atrial fibrillation and congestive heart failure, has a narrow therapeutic window. The blood levels required for therapeutic efficacy are close to those that can cause toxic symptoms. Traditional oral formulations often suffer from variable and incomplete absorption, posing a risk to patients, especially those with abnormal gastrointestinal uptake[1].
Scope of the Invention
The patent introduces a novel method and preparation to enhance the bioavailability of digoxin. Here are the key aspects:
Formulation
The invention involves administering digoxin in a soft gelatin capsule containing a solution of digoxin. This formulation is designed to dissolve rapidly in the upper gastrointestinal tract, typically within 15 minutes, ensuring quick release and absorption of the drug[1].
Bioavailability
The use of a soluble capsule shell significantly increases the bioavailability of digoxin compared to conventional tablets. This method achieves blood levels similar to those obtained through intravenous administration, but with the convenience and safety of an oral formulation[1].
Dosage
The patent specifies that the dosage in these capsules is approximately 80% of the dosage used in conventional tablets, yet it achieves substantially the same blood levels of digoxin. This reduction in dosage helps in minimizing the risk of toxicity while maintaining therapeutic efficacy[1].
Claims of the Patent
The patent includes several claims that define the scope of the invention:
Method of Administration
- The method involves administering digoxin in a solution form within a soft gelatin capsule that dissolves in the upper gastrointestinal tract[1].
Formulation Composition
- The capsule contains a solution of digoxin, and the shell may include components like glycerin, sorbitol, water, preservatives, coloring agents, and opacifying agents[1].
Bioavailability Enhancement
- The invention claims that the use of this formulation results in higher bioavailability compared to traditional oral tablets and pediatric elixirs[1].
Clinical Benefits
- The patent highlights that this method reduces the risk of variable uptake and toxicity associated with conventional oral digoxin preparations, especially in patients with abnormal gastrointestinal mobility[1].
Patent Landscape
The patent landscape surrounding US 4,088,750 is complex and involves several related patents and technologies:
Prior Art
- Earlier patents, such as US 2765256A, dealt with injectable solutions of digoxin using solvents like propylene glycol, water, and alcohol. These solutions were aimed at improving the stability and potency of digoxin but did not address oral bioavailability[5].
Related Patents
- Other patents, like US 4002718A, also focused on gelatin-encapsulated digoxin solutions but did not achieve the same level of bioavailability enhancement as described in US 4,088,750[5].
Continuations and References
- The patent is a continuation-in-part of earlier applications (Ser. No. 444,961 and Ser. No. 453,000), which were abandoned. It also references other patents and publications, such as Remington's Practice of Pharmacy, for the manufacture of soft gelatin capsules[1].
Impact and Significance
The invention described in US 4,088,750 has significant clinical and practical implications:
Clinical Efficacy
- By enhancing the bioavailability of digoxin, this formulation improves the therapeutic outcomes for patients with heart conditions, reducing the risk of toxicity and variability in drug absorption[1].
Patient Safety
- The reduced dosage required to achieve the same therapeutic effect minimizes the risk of adverse effects, making the treatment safer for patients[1].
Pharmaceutical Innovation
- This patent represents a milestone in pharmaceutical formulation technology, demonstrating how innovative delivery systems can improve drug efficacy and safety.
Key Takeaways
- Enhanced Bioavailability: The patent introduces a method to significantly increase the bioavailability of digoxin using a soft gelatin capsule.
- Reduced Dosage: The formulation achieves therapeutic blood levels with a lower dosage, reducing the risk of toxicity.
- Clinical Benefits: It improves therapeutic outcomes and patient safety by minimizing variability in drug absorption.
- Patent Landscape: The invention is part of a broader landscape of pharmaceutical innovations aimed at improving drug delivery and efficacy.
Frequently Asked Questions (FAQs)
What is the main innovation of US 4,088,750?
The main innovation is the use of a soft gelatin capsule containing a solution of digoxin to enhance its bioavailability.
How does this formulation improve bioavailability?
The soft gelatin capsule dissolves rapidly in the upper gastrointestinal tract, releasing the digoxin solution quickly and ensuring higher absorption rates.
What are the clinical benefits of this formulation?
It reduces the risk of toxicity and variability in drug absorption, improving therapeutic outcomes and patient safety.
How does the dosage compare to conventional tablets?
The dosage in these capsules is approximately 80% of the dosage used in conventional tablets, yet it achieves substantially the same blood levels of digoxin.
What other patents are related to this invention?
Related patents include those dealing with injectable solutions and other gelatin-encapsulated digoxin formulations, such as US 2765256A and US 4002718A.
Cited Sources
- US4088750A - Method and preparation for increasing bioavailability of digoxin - Google Patents
- US2765256A - Injectable solutions of digoxin - Google Patents
- US4002718A - Gelatin-encapsulated digoxin solutions and method of preparing the same - Google Patents
