Intravaginal ring comprising polyurethane composition for drug delivery

Patent metadata

Field	Value
Publication number	US-9393311-B2
Application number	US-201113885665-A
Country	US
Kind code	B2
Filing date	Nov 15, 2011
Priority date	Nov 15, 2010
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

The invention is directed to an intravaginal drug delivery device comprising at least one pharmaceutically active substance, and a polyurethane copolymer, wherein the copolymer has the structure according to formula (I):

The invention is further directed to administering one or more pharmaceutically active substances to a patient in need thereof.

First claim

The invention claimed is:

1. An intravaginal drug delivery ring comprising at least two pharmaceutically active substances wherein the pharmaceutically active substances are tenofovir and UC781, and
a polyurethane copolymer, wherein the copolymer has the structure according to formula (I):

wherein,
SME1 and SME2 can be the same or different and denote a surface modifying end-group comprising a methylpolyethylene glycyol (MPEG), having a number average molecular weight ranging from 200 to 8000, linked to the polymer via a urethane or urea bond resulting from the reaction of an amine- or alcohol-terminated surface modifying end group with an isocyanate group;
SS1, SS2, and SS3 denote soft-segments, wherein
SS 1 is a polyether diol selected from polyethylene oxide (PEO) diol, polytetramethylene oxide (PTMO) diol, polyhexamethylene oxide diol (PHMO), polypropylene oxide (PPO) diol, copolymer of ethylene glycol and propylene glycol (PEG-co-PPO) diol, and mixtures thereof;
SS2 is a hydroxyl or amine-terminated silicone polymer having a number average molecular weight ranging from 500 to 5000 g/mol; and
SS3 is a soft-segment selected from polycarbonate diol and polyester diol, and mixtures thereof;
HS denotes a hard-segment comprising a diisocyanate selected from the group consisting of hexamethylene diisocyanate (HMDI) and isophorone diisocyanate (IPDI) and combinations thereof,
x, y and z are the same or different and each is an integer equal to or greater than zero and at least two of x, y and z are not zero; and
wherein the copolymer has a number average molecular weight ranging from 50,000 to 350,000 g/mol and a swollen hardness of at least 30 A, and
wherein two or more pharmaceutically active substances are homogeneously distributed throughout the polyurethane copolymer.

2. Device according to claim 1 , wherein the mean daily flux of at least one of the pharmaceutically active substances is greater than 0.1 μg/mm 2 /d.

3. Device according to claim 1 , wherein the polyurethane copolymer comprises 15-35 weight % of at least one soft segment, 20-40 weight % of at least one hard segment and 0-2 weight % of a surface modifying end group; all related to the total weight of the dry polyurethane copolymer.

4. Device according to claim 1 , wherein the polyurethane copolymer is capable of absorbing water up to 50% by weight related to the total weight of the dry copolymer.

5. Device according to claim 1 , wherein the polyurethane composition is made by a process wherein the catalyst is stannous octoate is used.

6. Device according to claim 1 , further comprising antioxidants.

7. Device according to claim 1 , wherein the polymer is non-cytotoxic.

8. A method for administering one or more pharmaceutically active substances to a patient in need thereof, comprising inserting the device of claim 1 into the patient, whereby the active substance is released from the delivery device while the device resides in a subject's body.

Assignees

• Ward Robert S
• Wang Shanger
• Li Li
• Chalasani Durgaprasad
• Kiser Patrick
• Clark Meredith Roberts
• Dsm Ip Assets Bv
• Dsm Biomedical Inc

Inventors

• Ward Robert S
• Wang Shanger
• Li Li
• Chalasani Durgaprasad
• Kiser Patrick
• Clark Meredith Roberts

Classifications

• C08G18/73

  acyclic · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• A61K47/34 Primary

  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 title

• A61K9/0036 Primary

  Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms · CPC title

• A61K31/341

  not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine · CPC title