Immune-modifying nanoparticles for the treatment of inflammatory diseases

• US 9,913,883 B2
• Filed: 03/13/2014
• Issued: 03/13/2018
• Est. Priority Date: 03/13/2013
• Status: Active Grant

• Current Assignee: Oncour Pharma, Inc.
• Original Assignee: COUR Pharmaceuticals Development Company
• Inventors: Getts, Daniel
• Primary Examiner(s): Vanhorn, Abigail
• Application Number:
  US14/210,136
• Publication Number:
  US 20150010631A1
• Time in Patent Office: 1,461 Days
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/01 Hydrocarbons
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 31/78 of acrylic acid or derivatives thereof
• CPC Class Codes: A61K 39/0005 Vertebrate antigens from snakes A61K39/38
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: G01N 2800/7095 : Inflammation
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The current invention involves the administration of negatively charged particles, such as polystyrene, PLGA, or diamond particles, to subjects to ameliorate inflammatory immune responses. Additionally, the present invention describes methods of treating inflammatory diseases by administering these same negatively charged particles.

Claims

1. A method of inducing monocyte and/or neutrophil apoptosis in a subject comprising administering to said subject in need thereof an effective amount of a pharmaceutical composition comprising negatively charged poly(lactic-co-glycolic acid) (PLGA) particles and a pharmaceutically acceptable carrier, wherein said particles are free from attached or embedded peptides, antigens, and additional drugs or therapeutics, wherein the subject has an autoimmune disorder, an inflammatory disease is a transplant recipient, has ischemic reperfusion injury, atherosclerosis, has suffered from a cardiac infraction, or has a bacterial or viral infection, and wherein the administration induces monocyte and/or neutrophil apoptosis in the subject.

2. The method of claim 1, wherein the particles are carboxylated.

3. The method of claim 1, wherein the particles have a zeta potential between −

75 mV and 0 mV.

4. The method of claim 1, wherein the diameter of said negatively charged particles is between about 0.1 μ

m to about 10 μ

m.

5. The method of claim 1, wherein the subject has an ischemic reperfusion injury, atherosclerosis, or has suffered from a cardiac infarction.

6. The method of claim 1, wherein the diameter of said negatively charged particles is about 0.5 μ

m.

7. A method for removing pro-inflammatory mediators from the inflammatory milieu in a subject in need thereof with an inflammatory disorder comprising intravenously administering to said subject an effective amount a pharmaceutical composition comprising negatively charged poly(lactic-co-glycolic acid) (PLGA) particles and a pharmaceutically acceptable carrier, wherein said particles are free from attached or embedded peptides, antigens, and additional drugs or therapeutics, wherein the subject has an autoimmune disorder, an inflammatory disease is a transplant recipient, has ischemic reperfusion injury, atherosclerosis, has suffered from a cardiac infarction, or has a bacterial or viral infection, and wherein the administration removes pro-inflammatory mediators from the inflammatory milieu in the subject.

8. The method of claim 7, wherein said particles are carboxylated.

9. The method of claim 7, wherein the particles have a zeta potential between −

75 mV and 0 mV.

10. The method of claim 7, wherein the diameter of said negatively charged particles is between about 0.1 μ

m to about 10 μ

m.

11. The method of claim 7, wherein the subject has an ischemic reperfusion injury, atherosclerosis, or has suffered from a cardiac infarction.

12. The method of claim 7, wherein the diameter of said negatively charged particles is about 0.5 μ

m.

13. A method of inducing monocyte and/or neutrophil apoptosis in a subject in need thereof comprising intravenously administering to said subject an effective amount of a pharmaceutical composition comprising negatively charged particles and a pharmaceutically acceptable carrier, wherein said particles are free from attached or embedded peptides, antigens, and additional drugs or therapeutics;

wherein said particles are poly(lactic-co-glycolic acid) (PLGA) particles;

wherein said particles have a molar ratio of polylactic acid to polyglycolic acid of about 50;

50;

wherein said particles have a zeta potential between −

100 mV and 0 mV, wherein the subject has an autoimmune disorder, an inflammatory disease, is a transplant recipient, has ischemic reperfusion injury, atherosclerosis, has suffered from a cardiac infarction, or has a bacterial or viral infection and wherein the administration induces monocyte and/or neutrophil apoptosis in the subject.

14. The method of claim 13, wherein the particles are carboxylated.

15. The method of claim 13, wherein the diameter of said negatively charged particles is between 0.1 μ

m and 10 μ

m.

16. The method of claim 13, wherein the diameter of said negatively charged particles is about 0.5 μ

m.

17. The method of claim 13, wherein the subject has an ischemic reperfusion injury, atherosclerosis, or has suffered from a cardiac infarction.

18. A method for removing pro-inflammatory mediators from the inflammatory milieu in a subject in need thereof with an inflammatory disorder comprising intravenously administering to said subject an effective amount of a pharmaceutical composition comprising negatively charged particles and a pharmaceutically acceptable carrier, wherein said particles are free from attached or embedded peptides, antigens, and additional drugs or therapeutics;

wherein said particles are poly(lactic-co-glycolic acid) (PLGA) particles;

wherein said particles have a molar ratio of polylactic acid to polyglycolic acid to about 50;

50;

wherein particles have a zeta potential between −

100 mV and 0 mV wherein the subject has an autoimmune disorder, an inflammatory disease, is a transplant recipient, has ischemic reperfusion injury, atherosclerosis, has suffered from a cardiac infarction, or has a bacterial or viral infection, and wherein the administration removes pro-inflammatory mediators from the inflammatory milieu in the subject.

19. The method of claim 18, wherein said particles are carboxylated.

20. The method of claim 18, wherein the diameter of said negatively charged particles is between about 0.1 μ

m to about 10 μ

m.

21. The method of claim 18, wherein the subject has an ischemic reperfusion injury, atherosclerosis, or has suffered from a cardiac infarction.

22. The method of claim 18, wherein the diameter of said negatively charged particles is about 0.5 μ

m.

23. A method for removing pro-inflammatory mediators from the inflammatory milieu in a subject in need thereof with an inflammatory disorder comprising intravenously administering to said subject an effective amount of a pharmaceutical composition comprising negatively charged particles and a pharmaceutically acceptable carrier, wherein said particles are free from attached or embedded peptides, antigens, and additional drugs or therapeutics;

wherein said particles are poly(lactic-co-glycolic acid) (PLGA) particles;

wherein said particles have a molar ratio of polylactic acid to polyglycolic acid of about 50;

50;

wherein said particles have a zeta potential between −

100 mV and 0 mV;

wherein said subject has an ischemic reperfusion injury, atherosclerosis, or has suffered from a cardiac infarction, and wherein the administration removes pro-inflammatory mediators from the inflammatory milieu in the subject.