Mineral coated microparticles for sustained delivery of biologically active molecules

Patent metadata

Field	Value
Publication number	US-12465654-B2
Application number	US-201816500017-A
Country	US
Kind code	B2
Filing date	Apr 3, 2018
Priority date	Apr 3, 2017
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

Disclosed are formulations for providing an active agent. Formulations include a carrier including an active agent and mineral coated microparticles wherein an active agent is adsorbed to the mineral. Other formulations include a carrier including mineral coated microparticles wherein mineral coated microparticles include an active agent. Also disclosed are methods for sustained delivery of an active agent and methods for treating inflammatory diseases using a formulation for providing sustained delivery of an active agent.

First claim

What is claimed is:

1 . A formulation for providing an active agent comprising:
a carrier solution comprising:
at least a first unbound active agent; and
a mineral coated microparticle comprising a core and a mineral coating; and at least a second active agent bound to the mineral coated microparticle, wherein the mineral coated microparticle comprises the second active agent in an amount of 11.2 micrograms to 217.5 micrograms second active agent per milligram of microparticle, the first unbound active agent and the second active agent are an IL-1 antagonist, wherein the first unbound active agent and the second active agent are present in the carrier solution in a combined amount of 0.1 mg/ml to 10 mg/ml,
wherein the first unbound active agent, and the second active agent bound to the mineral coated microparticle are formulated together, and
wherein the formulation is in unit dose form.

2 . The formulation of claim 1 , wherein the second bound active agent is adsorbed to the mineral coating.

3 . The formulation of claim 1 , wherein the second bound active agent is adsorbed to the mineral coating, incorporated within the mineral coating, and combinations thereof.

4 . The formulation of claim 1 , wherein the first unbound active agent is selected from the group consisting of an IL-1 antagonist; an IL-1F2 antagonist; an IL-1F3 antagonist; an IL-1F4 antagonist; an IL-IFS antagonist; an IL-1F6 antagonist; an IL-1F7 antagonist; an IL-1F8 antagonist; an IL-1F9 antagonist; an IL-IF 10 antagonist; an IL-1F 11 antagonist; an IL-1R antagonist; abatacept; rituximab; tocilizumab; anakinra; adalimumab; etanercept; infliximab; certolizumab; golimumab; and combinations thereof.

5 . The formulation of claim 1 , wherein the mineral coating comprises calcium, phosphate, carbonate, and combinations thereof.

6 . The formulation of claim 1 , wherein the mineral coating further comprises a halogen selected from the group consisting of chlorine, bromine, iodine, astatine and combinations thereof.

7 . The formulation of claim 1 , wherein the mineral coated microparticle comprises a core chosen from polymers, ceramics, metals, glass and combinations thereof.

8 . The formulation of claim 1 , wherein the second bound active agent is incorporated within the mineral coating.

9 . The formulation of claim 1 , wherein the mineral coated microparticle comprises a plurality of layers of mineral coating.

10 . A method for sustained delivery of active agents, the method comprising: administering the formulation of claim 1 .

11 . A method for treating an inflammatory disease in a subject in need thereof, the method comprising:
administering a formulation to the subject, wherein the formulation comprises a carrier solution comprising:
at least a first unbound active agent; and
a mineral coated microparticle comprising a mineral coating; and at least a second active agent bound to the mineral coated microparticle, and wherein the mineral coated microparticle comprises the second active agent in an amount of 11.2 microgram to 217.5 micrograms second active agent per milligram of microparticle, the second active agent and the first unbound active agent both being an IL-1 antagonist, wherein the first unbound active agent and the second active agent are present in the carrier solution in a combined amount of 0.1 mg/ml to 10 mg/ml,
wherein the first unbound active agent and the second active agent bound to the mineral coated microparticle are formulated together, and wherein the formulation is in unit dose form.

12 . The method of claim 11 , wherein the first unbound active agent is selected from the group consisting of an IL-1 antagonist; an IL-1F2 antagonist; an IL-1F3 antagonist; an IL-1F4 antagonist; an IL-1F5 antagonist; an IL-1F6 antagonist; an IL-1F7 antagonist; an IL-1F8 antagonist; an IL-1F9 antagonist; an IL-1F 10 antagonist; an IL-1F 11 antagonist; an IL-1R antagonist; abatacept; rituximab; tocilizumab; anakinra; adalimumab; etanercept; infliximab; certolizumab; golimumab; and combinations thereof.

13 . The method of claim 11 , wherein the mineral coating comprises calcium, phosphate, carbonate, and combinations thereof.

14 . The method of claim 11 , wherein the mineral coating further comprises a halogen.

15 . The method of claim 11 , wherein the mineral coated microparticle comprises a core chosen from polymers, ceramics, metals, glass and combinations thereof.

16 . The method of claim 11 , wherein the second bound active agent is adsorbed to the mineral coating, is incorporated within the mineral coating, and combinations thereof.

17 . The method of claim 11 , wherein the mineral coated microparticle comprises a plurality of layers of mineral coating.

18 . A method for treating post-surgery inflammation in a subject in need thereof, the method comprising administering the formulation of claim 1 to the subject.

19 . The formulation of claim 1 , wherein the microparticle has a binding efficiency of second active agent of from 17% to 90%.

20 . The formulation of claim 1 , wherein the mineral coated microparticle is coated with two or more mineral coatings.

21 . The formulation of claim 20 , wherein each mineral coated layer independently comprises an active agent.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Murphy William L
• Clements Anna
• Chamberlain Connie
• Vanderby Ray

Classifications

• A61K9/167 Primary

  with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface (with further drug-free outer coating A61K9/5073) · CPC title

• A61K9/1611

  Inorganic compounds · CPC title

• A61K47/6927

  the form being a solid microparticle having no hollow or gas-filled cores · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• A61K2039/505

  comprising antibodies · CPC title