Detailed Analysis of the Scope and Claims of United States Patent 5,288,505
Introduction
United States Patent 5,288,505, titled "Extended release form of diltiazem," was granted on February 22, 1994, to inventors Deboeck et al. This patent is significant in the pharmaceutical field, particularly for the development of extended-release formulations of the drug diltiazem.
Background of the Invention
Diltiazem, a calcium channel blocker, has been known for over 20 years and is used to treat hypertension, angina, and certain heart rhythm disorders. The synthesis of diltiazem is described in earlier patents, such as German patent 1,805,714 and U.S. Pat. No. 3,562,257[1][4].
Scope of the Invention
The patent introduces novel galenic forms of diltiazem characterized by an extended-release mechanism. This innovation allows for excellent bioavailability while avoiding peak plasma concentrations, enabling the maintenance of diltiazem plasma concentrations within a desired effective range with simplified once-daily administration[1][4].
Key Components
- Beads: The medicine is constituted by beads containing diltiazem or its salt (such as the hydrochloride) and at least one wetting agent.
- Coating: The beads are coated with at least one polymer-based microporous membrane.
- Dosage Forms: The coated beads are contained in capsules, little bags, or dosage dispensers[1][4].
Claims of the Patent
The patent includes several claims that define the scope of the invention:
Claim 1
The patent claims a medicine containing diltiazem or its salt for extended release, comprising beads with diltiazem or its salt and a wetting agent, coated with a polymer-based microporous membrane[1].
Claim Details
- The beads are prepared using conventional techniques.
- The coating process involves applying a coating suspension to the beads, which can be done using various methods such as fluidized bed coating or top spraying[1][4].
- The coating suspension may include a variety of components such as fatty acid esters of sucrose or xylose, glycerides of sucrose, and other polymers[1].
Manufacturing Process
The patent describes a detailed process for obtaining the extended-release form of diltiazem:
Bead Preparation
- Beads are prepared by mixing diltiazem or its salt with a wetting agent.
- This mixture is then formed into beads using conventional techniques[1][4].
Coating Process
- The beads are coated with a polymer-based microporous membrane.
- Examples include using a fluidized bed coater equipped with a "wurster" system or a top spraying technique in a fluidized bed[1][4].
Examples and Testing
The patent provides several examples of how the beads were prepared and coated, along with the results of dissolution tests:
Example 1
- Beads were coated in a STREA-1 (Aeromatic) fluidized bed using the "top spraying" technique.
- The coated beads were dried at 50°C for 16 hours[4].
Example 2
- Beads were coated using a fluidized bed coater equipped with a "wurster" system.
- The coated beads were dried at 45°C for 15 hours[4].
Patent Landscape
The patent 5,288,505 is part of a broader patent landscape related to extended-release formulations of diltiazem.
Related Patents
- U.S. Pat. No. 5,529,791: This patent, also related to extended-release forms of diltiazem, was issued as a continuation of the application that led to U.S. Pat. No. 5,288,505. It involves similar claims and manufacturing processes[2][4].
Litigation and Enforcement
The patent was involved in litigation, notably in the case of Biovail Corp. Intern. v. Andrx Pharmaceuticals, Inc., where Biovail alleged infringement of the '791 patent by Andrx's filing of an Abbreviated New Drug Application (ANDA) for a bioequivalent formulation of Tiazac®, a brand name drug covered by the '791 patent[2].
Impact and Significance
The extended-release form of diltiazem described in this patent has significant clinical and commercial implications:
Clinical Benefits
- Simplified administration: Once-daily dosing improves patient compliance.
- Reduced peak plasma concentrations: Minimizes side effects and maintains therapeutic levels[1][4].
Commercial Impact
- The patent protected the intellectual property of the inventors and their assignees, allowing them to market the drug exclusively.
- The litigation surrounding this patent highlights the importance of patent protection in the pharmaceutical industry[2].
Key Takeaways
- Extended-Release Mechanism: The patent introduces a novel extended-release form of diltiazem, enhancing bioavailability and reducing peak plasma concentrations.
- Manufacturing Process: Beads containing diltiazem or its salt and a wetting agent are coated with a polymer-based microporous membrane.
- Patent Landscape: Part of a broader landscape including related patents and litigation.
- Clinical and Commercial Impact: Simplifies administration, reduces side effects, and protects intellectual property.
FAQs
What is the main innovation of U.S. Pat. No. 5,288,505?
The main innovation is the development of an extended-release form of diltiazem, allowing for once-daily administration and maintaining therapeutic plasma concentrations without peak levels.
How are the beads prepared and coated according to the patent?
Beads are prepared by mixing diltiazem or its salt with a wetting agent and then coated with a polymer-based microporous membrane using techniques such as fluidized bed coating or top spraying.
What are the clinical benefits of the extended-release form of diltiazem?
The extended-release form simplifies administration to once daily, improves patient compliance, and reduces peak plasma concentrations, thereby minimizing side effects.
Was this patent involved in any litigation?
Yes, the patent was involved in litigation, notably in the case of Biovail Corp. Intern. v. Andrx Pharmaceuticals, Inc.
How does the patent protect the intellectual property of the inventors?
The patent protects the specific method of preparing and coating the beads, as well as the composition of the extended-release formulation, preventing others from manufacturing and selling a bioequivalent formulation without permission.
Sources
- US5288505A - Extended release form of diltiazem - Google Patents
- Biovail Corp. Intern. v. Andrx Pharmaceuticals, Inc. - Justia
- Patent Analytics - SLWIP
- US5529791A - Extended release form of diltiazem - Google Patents
- US5288505.pdf - Google Patent Images
