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US-20260124160-A1 - PHARMACEUTICAL FORMULATIONS OF CURCUMIN AND/OR RESVERATROL COMPOUNDS

US20260124160A1US 20260124160 A1US20260124160 A1US 20260124160A1US-20260124160-A1

Abstract

A pharmaceutical composition comprising: (a) a resveratrol compound such as resveratrol, a curcumin compound such as curcumin, or a combination thereof; (b) an osmolality adjusting agent, and (c) a non-ionic surfactant, the pharmaceutical composition having an osmolality value ranging from 300±70 mOsm/kg. Also provided herein are therapeutic applications for the pharmaceutical compositions provided herein.

Inventors

  • Yu-Fang LING

Assignees

  • CALIWAY BIOPHARMACEUTICALS CO., LTD.

Dates

Publication Date
20260507
Application Date
20251106

Claims (18)

  1. 1 . A pharmaceutical composition, comprising a biologically active agent, a non-ionic surfactant hydrophilic-lipophilic balance (HLB) value ≥10, and an osmolality adjusting agent; wherein the biologically active agent comprises a curcumin compound, a resveratrol compound, or a combination thereof, wherein the pharmaceutical composition has an osmolality value ranging from 300±70 mOsm/kg, optionally wherein the pharmaceutical composition has a pH value ranging from 3 to 8.5.
  2. 2 . The pharmaceutical composition of claim 1 , wherein the curcumin compound is curcumin; and/or wherein the resveratrol compound is resveratrol.
  3. 3 . The pharmaceutical composition of claim 2 , wherein the biologically active agent comprises curcumin, the concentration of which in the composition is 0.04% to 5% by weight.
  4. 4 . The pharmaceutical composition of claim 3 , wherein the concentration of curcumin in the composition is about 0.1% to 2.5% by weight.
  5. 5 . The pharmaceutical composition of claim 3 , wherein the pH of the composition ranges from about 5.5 to about 8.5.
  6. 6 . The pharmaceutical composition of claim 2 , wherein the biologically active agent comprises resveratrol, the concentration of which in the composition is 0.04% to 20% by weight.
  7. 7 . The pharmaceutical composition of claim 6 , wherein the concentration of resveratrol in the composition is about 0.05% to 5% by weight.
  8. 8 . The pharmaceutical composition of claim 6 , wherein the composition has a pH ranging from about 4.5 to about 8.5.
  9. 9 . The pharmaceutical composition of claim 1 , wherein the non-ionic surfactant comprises PEGylated oils, polyoxyethylene, polyoxyethylene castor oil derivatives, or a combination thereof.
  10. 10 . The pharmaceutical composition of claim 9 , wherein the non-ionic surfactant comprises polyoxyl-35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 15 hydroxystearate or a combination thereof.
  11. 11 . The pharmaceutical composition of claim 1 , wherein the composition comprises the non-ionic surfactant at a concentration of 5% to 99% by weight.
  12. 12 . The pharmaceutical composition of claim 1 , wherein the osmolality adjusting agent comprises an organic agent selected from the group consisting of dextrose, mannitol, sorbitol, glycerin, and propylene glycol, an inorganic compound selected from the group consisting of sodium chloride, potassium chloride, dibasic potassium phosphate, sodium hydrogen phosphate, sodium citrate dihydrate, and sodium sulfite.
  13. 13 . The pharmaceutical composition of claim 12 , wherein the osmolality adjusting agent at a concentration of 0.05% to 0.9% by weight; optionally wherein the osmolality adjusting agent is sodium chloride.
  14. 14 . The pharmaceutical composition of claim 1 , wherein the composition has a weight ratio of the biologically active agent to non-ionic surfactant ranging from 1:5 to 1:500.
  15. 15 . The pharmaceutical composition of claim 1 , wherein the non-ionic surfactant and the biologically active agent form a plurality of nanoparticles.
  16. 16 . The pharmaceutical composition of claim 15 , wherein the nanoparticles have an average particle size of up to 200 nm and a polydispersity index (PDI) value of up to 0.4.
  17. 17 . A method for reducing fat or adipocytes in a subject, comprising: administering to a subject in need thereof an effective amount of a pharmaceutical composition set forth in claim 1 .
  18. 18 . A method for alleviating a condition caused by lipoma in a subject, comprising: administering to a subject in need thereof an effective amount of a pharmaceutical composition set forth in claim 1 .

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of the filing date of U.S. Provisional Application No. 63/716,970, filed Nov. 6, 2024, the entire contents of which is incorporated by reference herein. BACKGROUND Curcumin and resveratrol are naturally-occurring compounds with various beneficial effects, including anti-inflammatory and anti-oxidant activities. As such, they are widely used in pharmaceutical compositions to benefit treatment of various diseases and disorders. Subcutaneous (SC) administration of pharmaceutical formulations is widely used to effectively deliver different drugs to human patients. SC offer highs bioavailability and rapid onset of action and is considered near-ideal pharmacokinetically, less painful, and less prone to infections. Nonetheless, SC injections can involve a delayed response due to absorption at injection site and can cause injection site reactions, including pain that may lead to non-adherence. Injection site pain (ISP) is a subjective side effect that can impact treatment experience and patient adherence. It can be caused by various factors, such as needle features, volume, site and speed of injection, as well as features associated with the formulation (e.g., osmolality, viscosity, and pH). St Clair-Jones et al., Rheumatology and Therapy, vol. 7(4):741-757 (2020). SUMMARY The present disclosure is based, at least in part, on the development of compositions comprising curcumin, resveratrol, or a combination thereof with suitable osmolality values. Such compositions are expected to improve patient experience when delivered by subcutaneous injection (e.g., less pain at the injection site, less edema at the injection site, less inflammatory response at the injection site and/or no or slight subcutaneous hemorrhage). Accordingly, the present disclosure provides, in some aspects, a pharmaceutical composition, comprising a biologically active agent, a non-ionic surfactant hydrophilic-lipophilic balance (HLB) value ≥10, and an osmolality adjusting agent. The biologically active agent may comprise a curcumin compound (e.g., curcumin), a resveratrol compound (e.g., resveratrol), or a combination thereof. The pharmaceutical composition may have an osmolality value ranging from 300±70 mOsm/kg (e.g., 300±30 mOsm/kg). In some instances, the pharmaceutical composition has a pH value ranging from 3 to 8.5, for example, from 4 to 8.2, or from 4.5 to 7.8. In some examples, the pharmaceutical composition has a pH value ranging from 5.0 to 6.0, for example, 5.6. In some embodiments, the pharmaceutical composition may comprise curcumin at a concentration ranging from 0.04% to 5% by weight. In some examples, the concentration of curcumin in the composition ranges from 0.1% to 2.5% by weight. In one specific example, the concentration of curcumin in the composition can be about 0.4% by weight. In such a curcumin-containing pharmaceutical composition, the pH of the composition may range from about 5.5 to about 8.5. Alternatively or in addition, the pharmaceutical composition may comprise or further comprise resveratrol at a concentration of 0.04% to 20% by weight. In some examples, the concentration of resveratrol in the composition ranges from 0.05% to 5% by weight. In some specific examples, the concentration of resveratrol in the composition ranges from 0.05% to 2.5% by weight. When the pharmaceutical composition comprises resveratrol, its pH value may range from about 4.5 to about 8.5. In some embodiments, the pharmaceutical composition provided herein comprises one or more non-ionic surfactants. Examples include a PEGylated oils, polyoxyethylene, polyoxyethylene castor oil derivatives, polyoxy ethylene, polyoxyl castor oil, polyoxyl hydrogenated castor oil, or a combination thereof. In some examples, the non-ionic surfactant comprises polyoxyl-35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 15 hydroxystearate. or a combination thereof. Alternatively or in addition, the composition comprises the non-ionic surfactant at a concentration of 5% to 99% by weight (e.g., 5% to 95%, 5% to 90%, 5% to 85%, 5% to 80%, or 5% to 75%). In some instances, the composition is free of water. In some embodiments, the osmolality adjusting agent in the composition may comprise an organic agent capable of adjusting osmolality values. Examples include dextrose, mannitol, sorbitol, glycerin, and/or propylene glycol. Alternatively or in addition, the osmolality adjusting agent can comprise an inorganic compound, for example, sodium chloride, potassium chloride, dibasic potassium phosphate, sodium hydrogen phosphate, sodium citrate dihydrate, and/or sodium sulfite. In some examples, the osmolality adjusting agent may comprise sodium chloride at a concentration of 0.05% to 0.9% by weight. In some embodiments, the composition has a weight ratio of the biologically active agent to the non-ionic surfactant ranging from 1:5 to 1:500. In some instances, the non-ionic surfactant