Zwitterionic polymer-insulin compositions and related methods
Inventors
Assignees
Publication Number
US-12257309-B2
Publication Date
2025-03-25
Expiration Date
2038-01-17
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Glucose-responsive zwitterionic polymer-insulin-saccharide compositions are provided according to aspects of the present disclosure which include a zwitterionic polymer, an insulin moiety, a saccharide moiety, and a saccharide binding molecule. Methods of use of glucose-responsive zwitterionic polymer-insulin-saccharide compositions according to aspects of the present disclosure include administration to human patients to alleviate conditions, such as diabetes, which are responsive to administration of insulin.
Core Innovation
The invention provides glucose-responsive zwitterionic polymer-insulin-saccharide compositions that comprise a zwitterionic polymer, an insulin moiety, a saccharide moiety, and a saccharide binding molecule such as a lectin. The compositions are formed so that the lectin binds to the saccharide incorporated within the zwitterionic polymer-insulin-saccharide structure, enabling glucose-responsiveness. This structure allows the controlled release of insulin in response to ambient glucose concentration, as the interaction between the saccharide and the lectin is competed by glucose.
The compositions may be formulated by polymerizing a zwitterionic monomer, an insulin-containing monomer, and a saccharide-containing monomer, with additional variants including a hydrogel carrier that encapsulates these components to form a hydrogel-encapsulated, glucose-responsive composition. Specific saccharides such as mannose can be used to target selectivity towards certain lectins like Concavalin A, enabling precise glucose-triggered insulin release. These materials are also amenable to further modification, such as covalent linkage of the saccharide binding molecule to another polymer or hydrogel, further improving retention and tunability.
The problem addressed by this invention is the ongoing need for compositions including insulin that can treat diabetes and other disorders where exogenously administered insulin is beneficial. Current insulin therapies do not provide glucose-responsivity in a self-regulated manner, leading to risks of hypoglycemia or suboptimal glycemic control. The described compositions directly respond to glucose levels, thereby aiming to maintain euglycemia and reduce risks associated with insulin therapy.
Claims Coverage
The claims cover two main inventive features related to compositions containing a zwitterionic polymer-insulin-saccharide complex and its physical mixture with lectins to achieve glucose-responsivity, including further encapsulation in a hydrogel carrier.
Glucose-responsive zwitterionic polymer-insulin-saccharide composition with lectin binding
A composition comprising: - a zwitterionic polymer-insulin-saccharide composition that includes a zwitterionic polymer-insulin component covalently bonded to a saccharide or saccharide monomer; - a lectin in physical mixture with the zwitterionic polymer-insulin-saccharide composition, where the lectin binds specifically to the saccharide portion of the composition; - the combination forms a glucose-responsive system due to the competitive binding of glucose to the lectin, enabling insulin release in response to elevated glucose levels. This inventive feature enables the formulation of compositions that directly modulate insulin release based on glucose concentration through specific molecular interactions.
Hydrogel encapsulation of glucose-responsive zwitterionic polymer-insulin-saccharide composition
A composition comprising: - the glucose-responsive zwitterionic polymer-insulin-saccharide composition (as above), where the physical mixture is further encapsulated by a hydrogel carrier; - formation of a hydrogel-encapsulated glucose-responsive zwitterionic polymer-insulin-saccharide composition. This enables the immobilization and controlled release of the active composition, providing structural support and improving in vivo application potential.
The claim coverage establishes protection for compositions that combine zwitterionic polymer-insulin-saccharide molecules with lectins to create glucose-responsive insulin delivery systems, including formulations where these entities are encapsulated within a hydrogel carrier for enhanced performance.
Stated Advantages
Provides glucose-responsive release of insulin, enabling correction of hyperglycemia at high glucose concentrations and prevention of hypoglycemia at low glucose concentrations.
Conjugation of zwitterionic polymer to insulin does not reduce bioactivity and improves pharmacokinetics and pharmacological activity compared to unconjugated insulin.
Allows for tunable control of insulin release kinetics by modifying the composition or using hydrogel encapsulation.
Compositions such as the macrogel formulation show sustained insulin release and durability for long-term blood glucose control after subcutaneous implantation.
Hydrogel encapsulation and covalent anchoring of the lectin minimize leaching and improve stability of the delivery system.
Documented Applications
Treatment or management of type 1 diabetes, type 2 diabetes, gestational diabetes, or pre-diabetes by administering the described compositions.
Subcutaneous implantation of hydrogel-encapsulated, glucose-responsive zwitterionic polymer-insulin-saccharide compositions to provide long-term glucose control.
Use in medical devices including implantable sensors, prostheses, artificial joints, breast implants, cochlear implants, dental implants, contact lenses, artificial heart valves, artificial blood vessels, pacemakers, left ventricular assist devices, blood vessel grafts, stents, and various tubing such as urinary catheters or endotracheal tubes, by coating or incorporating the composition on or within the device.
Systemic or local administration in human or animal subjects via intravenous, intramuscular, subcutaneous, oral, or other common drug administration routes.
Interested in licensing this patent?