JP-2026514370-A - Flexible implantable depot for controlled drug release

Abstract

Implantable depots for delivering therapeutic agents, as well as related systems and methods, are provided. In some embodiments, an implantable depot for treating pain includes a therapeutic area comprising a polymer, an analgesic, and a plasticizer. The therapeutic area may be configured to release the analgesic over a treatment period of at least three days when implanted in vivo. The implantable depot may have a flexural modulus in the range of 1 MPa to 400 MPa.

Inventors

• ハンコック， ジャッキー ジョー
• シート， ダニエル ブーン リム
• スチュワート， クレア アイリーン
• スー， ジェイムス
• テウ， クーン キアト
• ガーティ－タゴエ， エシ ビー．
• ヒューイット， デイビッド ジェイ．
• リー， シンシア アール．
• リー， ウェイ リ
• リム， ミン シュー
• ウン， イー テン
• ルアン， パトリック エイチ．
• サムスディン， ノーファティン

Assignees

• ファウンドリー セラピューティクス， インコーポレイテッド

Dates

Publication Date

20260511

Application Date

20240328

Priority Date

20230329

Claims (20)

1. An implantable depot for treating pain comprises a therapeutic area containing a polymer, an analgesic, and a plasticizer, and is configured to release the analgesic over a treatment period of at least three days when implanted in vivo. The implantable depot has a flexural modulus in the range of 1 MPa to 400 MPa. Planted depot.
2. The planted depot according to claim 1, wherein the plasticizer is hydrophilic.
3. The planting-type depot according to claim 1, wherein the plasticizer is hydrophobic.
4. The implantable depot according to any one of claims 1 to 3, wherein the plasticizer comprises one or more of the following: triglycerides, fatty acid esters, lactic acid esters, citrates, phthalates, glycerol esters, sebacates, monoglyceride esters, benzyl derivatives, polyethylene glycol, polysorbates, diols, or triols.
5. The implantable depot according to any one of claims 1 to 4, wherein the plasticizer comprises one or more of triacetin, diethyl phthalate, benzyl benzoate, or glycerol.
6. The implantable depot according to any one of claims 1 to 5, wherein the relative energy difference (RED) between the plasticizer and the polymer is equal to or less than 1.
7. The implantable depot according to any one of claims 1 to 6, wherein the vapor pressure of the plasticizer is equal to or less than 0.5 Pa at 25°C.
8. The implantable depot according to any one of claims 1 to 7, wherein the logP value of the plasticizer is within the range of -1.5 to 6, 0 to 4, or 2 to 4.
9. The implantable depot according to any one of claims 1 to 8, wherein the plasticizer constitutes 0.1% to 20% of the total mass of the therapeutic agent area.
10. The implantable depot according to any one of claims 1 to 9, wherein the plasticizer constitutes 0.1% to 20% of the total mass of the implantable depot.
11. The implantable depot according to any one of claims 1 to 10, wherein the therapeutic agent area comprises only a single plasticizer.
12. The implantable depot according to any one of claims 1 to 10, wherein the plasticizer is a first plasticizer, and the therapeutic area further comprises a second plasticizer.
13. The implantable depot according to claim 12, wherein the first plasticizer is triacetin and the second plasticizer is glycerol.
14. The implantable depot according to claim 12 or 13, wherein the therapeutic agent area further comprises a third plasticizer.
15. The implantable depot according to claim 14, wherein the first plasticizer is triacetin, the second plasticizer is glycerol, and the third plasticizer is benzyl benzoate.
16. The implantable depot according to any one of claims 1 to 15, wherein the therapeutic agent region has a first surface, a second surface opposite to the first surface, and an outer surface between the first surface and the second surface.
17. The implantable depot according to claim 16, wherein the first surface, the second surface, and the outer surface of the therapeutic agent region are exposed.
18. The implantable depot according to claim 16, further comprising a first control region covering the first surface of the therapeutic agent region, wherein the first control region comprises a polymer.
19. The implantable depot according to claim 18, wherein the first control region does not contain any plasticizer.
20. The implantable depot according to claim 18, wherein the first control region contains a plasticizer.

Description

Cross-reference to related applications This application claims priority to U.S. Provisional Application No. 63/492,980, filed on 29 March 2023, which is incorporated herein by reference in its entirety. Technical field: The present invention relates in general to implantable depots, and more particularly to implantable depots and related systems and methods for delivering therapeutic agents. Background: Implantable systems for controlled release of therapeutic agents offer advantages over other drug delivery methods, such as oral or parenteral administration. Devices fabricated from biocompatible and/or biodegradable polymers and therapeutic agents can be implanted in clinically desirable anatomical locations, thereby resulting in local delivery of the selected drug. This local delivery allows a significant proportion of the drug to reach the intended target, while avoiding undesirable systemic side effects. However, these systems often suffer from a lack of a true controlled release mechanism, typically resulting in a burst release of the therapeutic agent upon contact with surrounding physiological fluids, followed by the release of the remaining drug. The controlled, sustained release of therapeutic agents can offer clinical benefits in certain environments. In particular, implanting biodegradable carriers that hold large doses of therapeutic agents may be desirable for controlled, sustained release over time. This can be especially valuable when the therapeutic agent-loaded carrier is implanted in conjunction with an intervention or surgical procedure, either together with or as part of an implantable medical device. Therefore, a biocompatible implantable system capable of providing highly controlled release of therapeutic agents is needed. Figure 1A is a partial schematic diagram of an implantable depot configured according to an embodiment of the present invention. Figure 1B is a partial schematic diagram of another implantable depot configured according to an embodiment of the present invention. Figure 1C is a partial schematic diagram of yet another implantable depot configured according to an articulation of the present invention. Figure 2A is a top view of a rectangular depot configured according to an embodiment of the technology of the present invention. Figure 2B is a side view of the rectangular depot shown in Figure 2A. Figure 3A is a top view of a triangular depot having holes, configured according to an embodiment of the present invention. Figure 3B is a side view of the triangular depot shown in Figure 3A. Figure 4A is a top view of a triangular depot having holes configured according to an embodiment of the present invention. Figure 4B is a side view of the triangular depot shown in Figure 4A. Figure 4C is a top view of another triangular depot having holes configured according to an articulation of the present invention. Figure 4D is a top view of yet another triangular depot having holes configured according to an articulation of the present invention. Figure 4E is a top view of a triangular depot having holes configured according to an articulation of the present invention. Figure 4F is a top view of another triangular depot having holes configured according to an articulation of the present invention. Figure 4G is a top view of a triangular depot having holes configured according to an embodiment of the present invention. Figure 4H is a top view of yet another triangular depot having holes configured according to an articulation of the present invention. Figure 5A is a top view of an arrowhead-shaped depot configured according to an embodiment of the present invention. Figure 5B is a top view of a rhomboid-shaped depot configured according to an embodiment of the present invention. Figure 5C is a top view of a rectangular depot configured according to an embodiment of the present invention. Figure 5D is a top view of a cross-shaped depot configured according to an embodiment of the present invention. Figure 5E is a top view of an L-shaped depot configured according to an embodiment of the present invention. Figure 5F is a top view of a circular depot configured according to an embodiment of the present invention. Figure 5G is a perspective view of a spherical depot configured according to an embodiment of the present invention. Figure 5H is a top view of a rhomboid-shaped depot configured according to an articulation of the present invention. Figure 6 is a scanning electron microscope image of a portion of an implantable depot. Figure 7A is a graph showing in vitro elution data for implantable depots. Figure 7B is another graph showing in vitro elution data for implantable depots. Figure 8A is a scanning electron microscope image of an implanted depot in which approximately 25% of the material has been eluted. Figure 8B is a scanning electron microscope image of an implanted depot in which approximately 75% of the material has been eluted. Figure 9A is a graph showing the mean bupiva