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JP-2026514362-A - Sustained-release cancer treatment

JP2026514362AJP 2026514362 AJP2026514362 AJP 2026514362AJP-2026514362-A

Abstract

This specification discloses compositions for treating tumors in subjects requiring such treatment, comprising an emulsion comprising: an aqueous carrier; a liquid lipid phase dispersed as droplets in the aqueous carrier; and a first chemotherapeutic agent in the lipid phase. In certain embodiments, the first chemotherapeutic agent comprises a plurality of first chemotherapeutic agent crystals. In certain alternative embodiments, the first chemotherapeutic agent is dissolved in the lipid phase. In certain embodiments, the composition further comprises a plurality of second chemotherapeutic agent crystals in the aqueous carrier rather than in the lipid phase, the second plurality of chemotherapeutic agent crystals dissolve and elute from the emulsion at a faster rate than the first plurality of chemotherapeutic agent crystals. In certain embodiments, the composition further comprises one or more additional chemotherapeutic agents different from the first chemotherapeutic agent. [Selection Diagram] Figure 1

Inventors

  • テイラー，ウィリアム・ジェイ
  • プフレプセン，ケルシー

Assignees

  • インシツ バイオロジクス、インク．

Dates

Publication Date
20260511
Application Date
20240325
Priority Date
20230324

Claims (20)

  1. A composition for treating tumors in subjects requiring it, A composition comprising an emulsion containing an aqueous carrier; a liquid lipid phase dispersed as droplets in the aqueous carrier; and a first chemotherapeutic agent in the lipid phase.
  2. The composition according to claim 1, wherein the first chemotherapeutic agent comprises a plurality of first chemotherapeutic agent crystals.
  3. The composition according to claim 1, wherein the first chemotherapeutic agent is dissolved in the lipid phase.
  4. The composition according to claim 2, further comprising a second plurality of chemotherapeutic agent crystals in an aqueous carrier rather than in a lipid phase, wherein the second plurality of chemotherapeutic agent crystals dissolve and elute from the emulsion at a faster rate than the first plurality of chemotherapeutic agent crystals.
  5. The composition according to claim 1, further comprising one or more additional chemotherapeutic agents different from the first chemotherapeutic agent.
  6. The composition according to claim 1, wherein the lipid phase contains triglycerides.
  7. The composition according to claim 1, wherein the aqueous carrier further comprises an emulsifier and a polyol, the emulsifier being tyramine-substituted hyaluronic acid, and the polyol being glycerol, present in an amount of about 0.25 to about 2.5% (w/v) of the composition.
  8. The composition according to claim 1, wherein the lipid phase further comprises phospholipids present in an amount of about 0.1% to about 2.0% of the lipid phase.
  9. The composition according to claim 1, wherein the lipid phase is approximately 10% to approximately 40% (w/v).
  10. The composition according to claim 1, wherein the stable emulsion further contains lecithin, the lecithin present in an amount of 0.1 to 5% (w/v) of the emulsion.
  11. The composition according to claim 1, wherein the emulsion further contains dextrose, the dextrose present in an amount of about 1-2% (w/v) of the emulsion.
  12. The composition according to claim 1, wherein the emulsion further contains sorbitol, the sorbitol present in an amount of about 0.1 to 2% (w/v) of the emulsion.
  13. The composition according to claim 1, wherein the lipid phase comprises about 15% to 80% (v/v) of soybean oil and about 15% to about 20% (v/v) of one or more medium-chain triglycerides.
  14. The composition according to claim 13, wherein the chemotherapeutic agent is present in an amount ranging from approximately 0.1 mg/g of soybean oil to approximately 300 mg/g of soybean oil.
  15. The composition according to claim 1, wherein the chemotherapeutic agent is selected from anthracyclines, mTOR inhibitors, VEGF-TKI agents, and immunostimulants.
  16. The composition according to claim 1, wherein the lipid phase comprises triptylate and/or stearate.
  17. The composition according to claim 2, wherein the lipid phase further comprises an oil and/or wax that is solid at 25°C in an amount (w/w) of about 5% to about 30% of the lipid phase, and the oil and/or wax coats the chemotherapeutic agent crystals.
  18. The composition according to claim 1, wherein the emulsion is stable for at least six months.
  19. The composition according to claim 1, wherein the chemotherapeutic agent is docetaxel and/or doxorubicin.
  20. A composition for treating tumors in subjects requiring it, A composition comprising an emulsion containing a lipid carrier phase; an aqueous phase dispersed as droplets in the lipid carrier phase; and a first chemotherapeutic agent in the aqueous phase.

Description

Cross-reference of related applications [001] This application claims priority to U.S. Provisional Patent Application No. 63/454,507, filed on 24 March 2023, pursuant to Section 119(e) of the U.S. Patent Act, which is incorporated herein by reference in its entirety. [002] Multifocal tumors, such as liver cancer, pancreatic cancer, kidney cancer, and lung cancer, offer few surgical treatment options. In the art, there is a need for effective compositions and methods to provide sustained local delivery of antitumor agents to maximize efficacy and minimize systemic effects. Similarly, there is a need for targeted therapy to a single tumor prior to tumor resection. [003] This specification discloses a composition for treating tumors in a target requiring such treatment, comprising an emulsion comprising: an aqueous carrier; a liquid lipid phase dispersed as droplets in the aqueous carrier; and a first chemotherapeutic agent in the lipid phase. In certain embodiments, the first chemotherapeutic agent comprises a plurality of first chemotherapeutic agent crystals. In certain alternative embodiments, the first chemotherapeutic agent is dissolved in the lipid phase. In certain embodiments, the composition further comprises a plurality of second chemotherapeutic agent crystals in the aqueous carrier rather than in the lipid phase, the second plurality of chemotherapeutic agent crystals dissolve and elute from the emulsion at a faster rate than the first plurality of chemotherapeutic agent crystals. In certain embodiments, the composition further comprises one or more additional chemotherapeutic agents different from the first chemotherapeutic agent. [004] According to certain embodiments, the lipid phase constitutes about 10% to about 40% (w/v) of the composition. In certain embodiments, the lipid phase comprises one or more triglycerides. In certain embodiments, the lipid phase comprises about 15% to 80% (v/v) of soybean oil and about 15% to about 20% (v/v) of one or more medium-chain triglycerides. In certain embodiments, the lipid phase comprises triptylate and/or stearate. In certain further embodiments, the lipid phase also comprises one or more oils and/or waxes. [005] In certain embodiments, the lipid phase further comprises oils and/or waxes that are solid at 25°C in an amount of about 5% to about 30% (w/w) of the lipid phase, the oils and/or waxes coating the chemotherapeutic agent crystals. [006] In certain embodiments, the aqueous carrier further comprises an emulsifier and a polyol. In certain embodiments, the emulsifier is, for example, a hyaluronic acid such as tyramine-substituted hyaluronic acid. In certain embodiments, the polyol is glycerol and is present in an amount of about 0.25 to about 2.5% (w/v) of the composition. [007] According to certain embodiments, the lipid phase further comprises phospholipids. In certain embodiments, the phospholipids are present in an amount of about 0.1% to about 2.0% of the lipid phase. According to certain further embodiments, the lipid phase further comprises antioxidants. In exemplary embodiments, the antioxidants are present in an amount of about 0.01% to about 1% (w/v) of the composition. [008] According to a particular embodiment, the emulsion further comprises lecithin. In a particular embodiment, lecithin is present in an amount of 0.1 to 5% (w/v) of the emulsion. [009] In a particular embodiment, the emulsion further comprises dextrose, which is present in an amount of about 1-2% (w/v) of the emulsion. [010] In certain embodiments, the chemotherapeutic agent is present in an amount ranging from about 0.1 mg/g soybean oil to about 300 mg/g soybean oil. In certain embodiments, the chemotherapeutic agent is selected from anthracyclines, mTOR inhibitors, VEGF-TKI agents, and immunostimulants. In further embodiments, the chemotherapeutic agent is docetaxel or doxorubicin. [011] Furthermore, this specification discloses a composition for treating tumors in a subject requiring such treatment, the composition comprising an emulsion comprising an aqueous carrier; a liquid lipid phase dispersed as droplets in the aqueous carrier; and a first chemotherapeutic agent in the lipid phase, wherein the first chemotherapeutic agent comprises a plurality of first chemotherapeutic agent crystals, and the liquid lipid phase further comprises one or more oils and/or waxes having a melting point greater than 25°C, the one or more oils and/or waxes coating the first plurality of chemotherapeutic agent crystals. In certain embodiments, the one or more oils and/or waxes are coconut oil and/or carnauba wax. In certain embodiments, the coconut oil and/or carnauba wax is present in an amount of about 3% to about 30% (w/w) of the lipid phase. [012] Furthermore, this specification discloses a composition for treating tumors in a target requiring such treatment, comprising an emulsion comprising: a lipid carrier phase; an aqueous phase dispersed as droplets in the lipid carrier phase;