Adiponectin peptidomimetics formulations
Inventors
Barman, Shikha P • Ward, Kevin L • Chen, Yugang
Assignees
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Publication Number
US-12201668-B2
Publication Date
2025-01-21
Expiration Date
Abstract
Disclosed are compositions and methods for the use of adiponectin peptidomimetics in therapeutic applications. The compositions can include a peptide, for example, D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH2, a solubilizer, a surfactant(s), a buffer, optionally boric acid and optionally mannitol. The osmolality of the composition can be between 260 to 330 mOsm/kg and the pH can be between 4.5 to 5.5. Methods of using the compositions in treating certain eye disease(s) are also disclosed.
Core Innovation
The disclosed invention relates to an ophthalmic therapeutic composition comprising a therapeutically effective amount of an adiponectin peptidomimetic having the formula of D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH2. The composition further includes a generally recognized as safe solubilizer and one or more generally recognized as safe surfactants, and the composition is formulated with specific physicochemical constraints.
The composition includes a buffer comprising boric acid and mannitol, wherein the osmolality is between 260 to 330 mOsm/kg and the pH is between 4.5 to 5.5. The disclosure also provides specific GRAS solubilizer and surfactant selections and describes acetate buffer systems using acetic acid and sodium acetate in combination with boric acid and mannitol.
In an atropine-induced dry-eye context, the disclosed formulations reduce corneal staining and maintain or increase tear break-up time and improve tear volume in a rabbit irritation and efficacy testing context, including corneal fluorescein staining, tear break-up time, and tear volume measurements.
Claims Coverage
The independent claim recites a composition with an adiponectin peptidomimetic plus GRAS solubilizer and GRAS surfactants, constrained to a buffer comprising boric acid and mannitol with osmolality 260–330 mOsm/kg and pH 4.5–5.5. The dependent claims refine the independent claim by selecting specific solubilizer and surfactant members and by specifying alternative and example weight-percent formulations including acetate buffer components and boric acid/mannitol buffer.
Adiponectin peptidomimetic-containing therapeutically effective composition
A composition comprising a therapeutically effective amount of an adiponectin peptidomimetic having the formula of D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH2.
Gras solubilizer and one or more gras surfactants
A generally recognized as safe solubilizer and one or more generally recognized as safe surfactants included in the composition.
Boric acid and mannitol buffer with constrained osmolality
A buffer comprising boric acid and mannitol, wherein the osmolality is between 260 to 330 mOsm/kg.
Constrained pH
Wherein the pH is between 4.5 to 5.5.
Specific gras solubilizer and specific surfactant members
The solubilizer is selected from polypropylene glycol, glycerol, PEG400 and propylene glycol; the surfactant is selected from Polysorbate 80, Tyloxapol, Poloxamer, PEG 40 Hydrogenated Caster Oil, PEG 35 Caster Oil and PEG 40 Sterate; and the buffer further comprises an acetate buffer.
By-weight composition ranges including peptide and acetate components
A composition that contains, by weight, specified ranges of D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH2, propylene glycol, Tyloxapol or Poloxamer, acetic acid, and sodium acetate.
Concrete by-weight formulation including boric acid and mannitol
A composition defined by weight percentages of the peptide D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH2 and excipients including propylene glycol, Tyloxapol, acetic acid, sodium acetate, boric acid, and mannitol.
Alternative enumerated percentage compositions
A composition selected from specific alternative formulations that vary the percentage of D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH2 along with differing amounts of propylene glycol, Tyloxapol or Poloxamer 188, acetic acid, and sodium acetate.
Specific weight-percent example including boric acid and mannitol
A specific weight-percent composition comprising D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH2, propylene glycol, Tyloxapol, acetic acid, sodium acetate, boric acid and mannitol.
Overall, the claim set covers an ophthalmic therapeutic composition built around an adiponectin peptidomimetic, combined with GRAS solubilizer and GRAS surfactants, and specifically buffered with boric acid and mannitol under constrained osmolality and pH. Dependent claims further narrow the scope via selectable solubilizer and surfactant members and by enumerating or exemplifying weight-percent formulations that include acetate buffer components and explicit boric acid and mannitol inclusion.
Stated Advantages
Reduced corneal staining.
Maintained or increased tear break-up time (TBUT).
Improved tear volume (TV).
Documented Applications
Ophthalmic therapy in an atropine-induced dry-eye model, including rabbit irritation studies with corneal fluorescein staining, tear break-up time (TBUT), and tear volume (TV) measurements.
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