United States Patent 4,880,631: Scope, Claim Structure, and US Landscape for Diltiazem L-Malate Osmotic Pumps
What does US 4,880,631 claim in plain scope terms?
US Patent 4,880,631 claims an osmotic pump drug-delivery device for controlled release of diltiazem L-malate. The claim center of gravity is a specific core composition plus a water-insoluble, water-permeable, solute-reflecting wall whose permeability and porosity are engineered using a pH-insensitive pore-forming additive dispersed through the wall matrix.
Core limitation (claims 1 and 20)
The drug reservoir (core) must include:
- Therapeutically effective amount of diltiazem L-malate
- Sodium bitartrate in an amount between 80 and 150% by weight relative to the diltiazem L-malate core component (as written: “diltiazem L-malate and between 80 and 150 percent by weight of sodium bitartrate”)
Claim 20 is broader in form but identical in substance: it claims an admixture of diltiazem L-malate with 80 to 150% by weight sodium bitartrate for use in a controlled-release delivery device.
Rate-controlling wall limitation (claim 1)
The osmotic pump wall must be:
- Rate controlling
- Water insoluble
- Fluid permeable with a permeability window:
- 6.96×10−18 to 6.96×10−14 cm³ sec/g
- Reflection coefficient < 0.5 (and dependent claim 6 narrows to < 0.1)
The wall is prepared from:
- (i) a polymer permeable to water but impermeable to solute
- (ii) 0.1 to 60 wt% of at least one pH-insensitive pore forming additive, dispersed throughout the wall
The pore forming additive is defined by functional “pH-insensitive” character, and claim 15 narrows the preferred additive species.
What are the technical claim pillars (and how narrow are they)?
Claim 1 builds a layered construct. Each layer narrows design space and increases enforceability by tying device function to measurable physical parameters.
1) Composition of the drug core
- Sodium bitartrate ratio: 80 to 150% by weight
- This is a hard numerical boundary that can screen-around by changing salt or ratio (but only if the alternative does not still fall within the claimed ratio).
2) Wall permeability and solute rejection
- Fluid permeability must fall in a defined range: 6.96×10−18 to 6.96×10−14 cm³ sec/g
- Reflection coefficient:
- independent: < 0.5
- dependent claim 6: < 0.1
These values matter because they tie scope to experimentally measurable transport properties rather than solely material identity.
3) Wall formulation via pH-insensitive pore-forming additive
- Pore-former load: 0.1 to 60 wt% (claim 1)
- Wall pores must meet dependent diameter ranges (claim 5 and claim 8)
- Dependent claim 15 further identifies specific pH-insensitive pore-former compounds (PEG, sorbitol, glucose).
4) Polymer selection tied to water-permeable/solute-impermeable behavior
- Claim 9 gives polymer classes for (i), including:
- cellulose esters
- acylated polysaccharides
- polyurethanes
- polymers of acrylic/methacrylic acid and esters
- poly(ortho ester)s
- polyacetals
- plus mixtures
Sub-claims 10-12 lock the family further.
What do the dependent claims add beyond claim 1?
The dependent claims primarily tighten numerical ranges and expand the optional architecture (external layer + other cardiovascular agents).
Drug load and salt load bands (claims 2 and 3)
- Diltiazem L-malate in core: 30 to 500 mg (claim 2)
- Sodium bitartrate in core: 30 to 500 mg (claim 3)
These constrain commercial formulations that use different fill amounts per device.
Pore-former composition control (claims 4 and 14)
- Pore forming additive may be:
- 0.1 to 50 wt% solid additive, and/or
- 0.1 to 40 wt% liquid additive
- Total pore forming additive not to exceed 60 wt% (claim 4)
- Claim 14 restates/clarifies: 0.1 to 50 wt% pore forming additive is used
Wall thickness and pore diameter (claims 5 and 8)
- Wall thickness: 20 to 500 microns (claim 5)
- Wall pore diameter: 10 angstroms to 25 microns (claim 5)
Claim 8 adds a broader wall thickness and pore distribution:
- Wall thickness: 1 to 1,000 microns
- 5 to 95% of pores between 10 angstroms and 100 microns
Reflection coefficient tightening (claim 6)
- Reflection coefficient < 0.1
Optional additives in wall system (claim 7)
- Plasticizer/flux regulating additives:
- 0 to 50 parts per 100 parts of (i) and (ii)
- Surfactant additive:
- 0 to 40 parts per 100 parts of (i) and (ii)
This gives formulation flexibility while keeping the core inventive transport properties.
Polymer subclassing (claims 9–13)
Claim 13 sets the pore forming additive species class:
- water
- alkali metal salts
- alkaline earth metal salts
- saccharides
- aliphatic polyols
- aromatic polyols
- mixtures
Claim 15 narrows pH-insensitive pore forming additive to:
- polyethylene glycol
- sorbitol
- glucose
- mixtures
External layer for additional cardiovascular therapy (claims 16–19)
Claim 16 adds:
- an external layer
- containing a pharmaceutically acceptable carrier
- and a therapeutically effective amount of a cardiovascular agent
Claim 17 lists cardiovascular agent families (broad enumeration), and claim 18 narrows to:
- angiotensin converting enzyme inhibitors (ACE inhibitors)
Claim 19 narrows further to specific ACE inhibitors:
- captopril
- enalapril
- lisinopril
Where does the patent sit in the US osmotic pump landscape?
US 4,880,631 is best positioned as an engineering claim set within osmotic delivery. The scope is not merely “diltiazem L-malate in an osmotic pump.” It requires a salt selection and loading ratio (sodium bitartrate 80–150%), plus a constructed wall with transport metrics (permeability and reflection coefficient) and a pH-insensitive pore former incorporated into a water-permeable/solute-impermeable polymer matrix.
That structure is the practical difference versus older osmotic pump claims that are often framed around general membrane formation and osmotic agents without tying to:
- specific permeability windows, and
- explicit “pH-insensitive pore-forming additive dispersed throughout said wall,” and
- measurable reflection coefficient thresholds.
Enforcement consequence: a competitor can potentially adopt the general osmotic pump concept while steering clear by altering any of these three anchors:
1) salt identity/ratio,
2) wall permeability/reflection,
3) pore-former identity/load.
Claim map for infringement-relevant design parameters
Below is a parameter-to-claim mapping for device builders.
| Parameter |
Must meet what |
Claim(s) |
| Drug |
diltiazem L-malate (therapeutically effective) |
1, 2 |
| Osmotic/solubilizing salt in core |
sodium bitartrate at 80–150% by weight |
1, 20 |
| Fill amount |
diltiazem L-malate 30–500 mg |
2 |
| Salt fill amount |
sodium bitartrate 30–500 mg |
3 |
| Wall polymer function |
water permeable/solute impermeable polymer (class list) |
1, 9 |
| Wall fluid permeability |
6.96×10−18 to 6.96×10−14 cm³ sec/g |
1 |
| Reflection coefficient |
< 0.5 (or < 0.1) |
1, 6 |
| Pore former dispersion |
0.1–60 wt% pH-insensitive pore former in wall |
1 |
| Pore former chemistry (preferred) |
PEG/sorbitol/glucose |
15 |
| Pore former wt% controls |
total pore former limits + solid/liquid splits |
4, 14 |
| Wall thickness |
20–500 microns (or 1–1,000 microns) |
5, 8 |
| Pore diameter |
10 angstroms–25 microns (or 10 angstroms–100 microns with distribution %) |
5, 8 |
| Optional excipients in wall |
plasticizer/flux regulating 0–50 pph; surfactant 0–40 pph |
7 |
| Optional external layer |
cardiovascular agent + carrier |
16 |
| External layer agent |
ACE inhibitor family |
18 |
| ACE inhibitor species |
captopril/enalapril/lisinopril |
19 |
How does claim 20 broaden or differ from claim 1?
Claim 20 is an admixture claim:
- “An admixture of diltiazem L-malate with between 80 and 150 percent by weight of sodium bitartrate in a drug delivery device…”
This can matter for enforcement strategy because an admixture claim can be used to attack conduct tied to formulation preparation, even if a party argues differences in the device architecture, depending on how the claim is construed and how “in a drug delivery device” is interpreted.
Where is the strongest risk area for generic or alternative formulators?
The highest risk sits where all anchors overlap:
1) Salt ratio: sodium bitartrate at 80–150% by weight relative to diltiazem L-malate.
2) Membrane transport: wall permeability and reflection coefficient within the numeric windows.
3) Pore forming additive: pH-insensitive additive dispersed at 0.1–60 wt%, with dependent constraints on pore size distribution.
If any one anchor is removed, the claim set can become easier to avoid because the device no longer meets the measurable transport constraints or does not contain the specific engineered pore-former system.
Practical patent landscape takeaways (US)
The core of US 4,880,631 is a narrow but technically deep osmotic-pump implementation for a single drug substance and salt system. In the US market, this typically means:
- Differentiation against earlier osmotic systems is grounded in transport metrics and pore-former engineering rather than only in “osmotic pump + drug.”
- Design-around is most feasible by changing:
- the core solubilizing/salt system,
- membrane polymer class,
- membrane permeability/reflection properties, or
- pore-former type and loading.
If a competitor keeps the salt ratio and only changes the pore former or polymer, they still may fall within the polymer and additive ranges unless they move outside the claimed species and load boundaries (and the wall transport parameters).
Key Takeaways
- US 4,880,631 claims an osmotic pump for controlled release of diltiazem L-malate built on two hard anchors: (i) sodium bitartrate core loading of 80–150% by weight and (ii) a rate-controlling water-insoluble wall with defined fluid permeability and reflection coefficient.
- Scope depends on measured membrane transport properties (permeability window and reflection coefficient thresholds), not only on polymer category and pore presence.
- The wall must incorporate 0.1–60 wt% pH-insensitive pore-forming additive dispersed throughout, with dependent claims tightening pore sizes, wall thickness, and pore distribution.
- The patent also includes formulation-related protection via an admixture claim (claim 20) and architecture-related extension via an external layer using specific cardiovascular agent classes (ACE inhibitors and specific ACE inhibitor examples).
FAQs
1) Is the salt system (sodium bitartrate) essential to claim scope?
Yes. Claim 1 requires a core containing diltiazem L-malate plus 80–150% by weight sodium bitartrate, and claim 20 claims the corresponding admixture.
2) Do the claims require specific wall permeability and reflection coefficient values?
Yes. Claim 1 requires fluid permeability 6.96×10−18 to 6.96×10−14 cm³ sec/g and reflection coefficient < 0.5, with dependent claim 6 narrowing to < 0.1.
3) Can a different pore former still fall within the claims?
Yes, if it is a pH-insensitive pore forming additive in the required 0.1–60 wt% range, but claim 15 lists preferred pore-formers (PEG, sorbitol, glucose).
4) Does the patent cover only the osmotic core, or also optional external layers?
It covers both. Claim 16 adds an optional external layer with a therapeutically effective cardiovascular agent, with claims 18–19 narrowing to ACE inhibitors and then to specific ACE inhibitor examples.
5) Is there protection beyond device structure?
Yes. Claim 20 covers an admixture of diltiazem L-malate with 80–150% by weight sodium bitartrate “in a drug delivery device,” which can broaden enforcement beyond membrane and wall microstructure arguments.
References
[1] US Patent 4,880,631, “Osmotic pump for the controlled release of diltiazem L-malate,” claims 1–20 (as provided in the prompt).
