DEVICE THAT DELIVERS A SUSTAINED LOW-DOSE OF A MYOPIA-SUPPRESSING DRUG, WHILE PRESERVING PUPILLARY FUNCTION AND ACCOMMODATION

• US 20160338947A1
• Filed: 05/19/2016
• Published: 11/24/2016
• Est. Priority Date: 05/19/2015
• Status: Active Grant

• Current Assignee: Amorphex Therapeutics Llc
• Original Assignee: Amorphex Therapeutics Llc
• Inventors: Leahy, Charles D., Ellis, Edward J.
• Granted Patent: US 10,010,502 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: G02B 1/043 Contact lenses
• CPC Class Codes: G02C 7/04 Contact lenses for the eyes disinfection or sterilisation of contact lenses A61L12/00

Abstract

A non-degradable topical ocular drug delivery device includes about 0.001% to about 10% w/w of at least one myopia-suppressing agent complexed with an immobile acid within a crosslinked polymer matrix. The cross-linked polymer matrix is configured to deliver the least one myopia-suppressing agent over an extended period of time at a concentration and rate that controls myopia progression while preserving pupillary function and accommodation.

Claims

1. A non-degradable topical ocular drug delivery device comprising about 0.001% to about 10% w/w of at least one myopia-suppressing agent complexed with an immobile acid within a crosslinked polymer matrix, the cross-linked polymer matrix being configured to deliver the at least one myopia-suppressing agent over an extended period of time at a concentration and rate that at least one of impedes, prevents, and controls myopia progression while preserving pupillary function and accommodation.

2. The device of claim 1, wherein the crosslinked polymer matrix defines a preformed body that is configured to be held on the sclera of an eye such that the preformed body is free of contact with and spaced from the cornea of the eye.

3. The device of claim 2, wherein the preformed body has an anterior surface and an opposing posterior surface for placement on the sclera, the posterior surface having a concave curved shape that is defined by a base curve shaped to fit the sclera.

4. The device of claim 1, wherein the cross-linked matrix defines a preformed body having a mass between about 50 mg to about 150 mg.

5. The device of claim 1, wherein the cross-linked matrix has a glass transition temperature less than 20°

C. and a water content less than 2% by weight.

6. The device of claim 5, wherein the cross-linked matrix includes at least 30% by weight of an alkyl ether.

7. The device of claim 6, wherein the alkyl ether is derived from at least one of a monomer having a formula:

8. The device of claim 7, further including at least one of acrylic and methacrylic acid.

9. The device of claim 6, wherein the alkyl ether is derived from at least one of a monomer having a formula:

10. The device of claim 1, wherein the cross-linked polymer matrix is formed of

an alkyl ether containing methacrylate monomer;

an alkyl ether crosslinking agent; and

methacrylic acid which comprises the immobile acid within the cross-linked polymer matrix.

11. The device of claim 10, wherein the alkyl ether containing methacrylate monomer comprises Di(ethyleneglycol) ethyl ether methacrylate.

12. The device of claim 10, wherein the alkyl ether crosslinking agent comprises polyethyleneglycol dimethacrylate.

13. The device of claim 1, wherein the myopia-suppressing agent comprises an anti-muscarinic drug selected from a group consisting of:

atropine, atropine sulphate monohydrate and pirenzepine.

14. The device of claim 1, wherein the myopia-suppressing agent comprises an anti-muscarinic drug selected from a group consisting of:

racanisodamine, cyclopentolate, homatropine, scopolamine, telenzepine, nuvenzepine and rispenzepine.

15. The device of claim 1, wherein the myopia-suppressing agent comprises a dopamine agonist selected from a group consisting of:

apomorphine, bromocriptine, quinpirole, levodopa or an adenosine agonist selected from the group consisting of adenosine, 7-methylxanthine, ATL-146e, 2-(1-octynyl)adenosine, CGS-21680, DPMA, regadenoson, UK-432,097, Limonene and 5′

-(N-Ethylcarboxamido)adenosine (NECA).

16. The device of claim 1, wherein the myopia-suppressing agent comprises atropine in a concentration range between about 0.02 and about 0.2% w/w polymer.

17. The device of claim 1, wherein the myopia-suppressing agent comprises atropine in a concentration range between about 0.02 and about 0.07% w/w polymer.

18. The device of claim 1, wherein the myopia-suppressing agent comprises pirenzepine in a concentration range between about 0.1 and about 3% w/w polymer.

19. The device of claim 18, wherein the concentration range is between about 0.1 and 1% w/w polymer.

20. The device of claim 1, wherein the extended period of time comprises at least 30 days.

21. The device of claim 1, wherein the extended period of time comprises at least 60 days.

22. The device of claim 1, wherein the extended period of time comprises at least 76 days.

23. The device of claim 1, wherein the preservation of pupillary function corresponds to a pupil dilation that is no more than 3 mm greater than a baseline pupil diameter and after the device has been in the eye for at least 24 hours.

24. The device of claim 23, wherein the pupil dilation is predominantly no more than 2 mm greater than the baseline pupil diameter and after the device has been in the eye for at least 24 hours.

25. The device of claim 1, wherein the myopia-suppressing agent comprises atropine having a concentration of about 0.05% w/w polymer.

29. A method for at least one of impeding, preventing, and controlling myopia progression, while maintaining functional pupil constriction and dilation and accommodative ability comprising the steps of:

inserting the non-degradable topical ocular drug delivery device of claim 1 into an eye.

26. A non-degradable topical ocular drug delivery device for at least one of impeding, preventing, and controlling myopia progression, the non-degradable topical ocular drug delivery device comprising:

a preformed body that is configured to fit and be held on an eye, the preformed body being formed of a cross-linked polymer matrix; and

about 0.001% to about 10% w/w of at least one myopia-suppressing agent complexed with an immobile acid within the crosslinked polymer matrix;

wherein the cross-linked polymer matrix is configured to deliver the at least one myopia-suppressing agent in sustained, controlled micro doses over an extended period of time while maintaining a pupil size increase of no greater than about 3 mm relative to a pupil dilation baseline after the preformed body has been in the eye for at least 24 hours and up to at least 30 days after insertion of the device in the eye.

27. The device of claim 26, wherein the pupil size increase is maintained between about 1 mm to about 3 mm relative to the pupil dilation baseline after the preformed body has been in the eye for at least 24 hours and up to at least 30 days after insertion of the device in the eye.

28. The device of claim 26, wherein the myopia-suppressing agent comprises atropine having a concentration of about 0.05% w/w polymer.