Intravaginal ring comprising polyurethane composition for drug delivery

Patent metadata

Field	Value
Publication number	US-9603932-B2
Application number	US-201614993826-A
Country	US
Kind code	B2
Filing date	Jan 12, 2016
Priority date	Nov 15, 2010
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

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):

Also, method comprising administering one or more pharmaceutically active substances to a patient in need thereof.

First claim

What is claimed is:

1. An intravaginal drug delivery device comprising:
a polyurethane copolymer having a number average molecular weight ranging from 50,000 to 350,000 g/mol and a swollen hardness of at least 30 A, the copolymer having the structure according to formula (I):

wherein,
SS1, SS2, and SS3 denote soft segments, with SS1 being 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 being a hydroxyl or amine-terminated silicone polymer having a number average molecular weight ranging from 500 to 5000 g/mol, and SS3 being 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 and z are the same or different and each is an integer equal to or greater than zero, y is an integer equal to or greater than one, and at least two of x, y, and z are not zero; and
SME1 and SME2 can be the same or different and each denotes a surface modifying endgroup comprising a methyl polyethylene glycol (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, and
at least one hydrophobic pharmaceutically active substance and at least one hydrophilic pharmaceutically active substance, said pharmaceutically active substances being homogenously distributed throughout the polyurethane copolymer.

2. The device according to claim 1 , wherein
said at least one hydrophobic pharmaceutically active substance comprises a compound selected from the group consisting of dapivirine, UC781, valdecoxib, allopurinol, acetohexamide, benzthiazide, chlorpromazine, chlordiazepoxide, haloperidol, indomethacine, lorazepam, methoxsalen, methylprednisone, nifedipine, oxazepam, oxyphenbutazone, prednisone, prednisolone, pyrimethamine, phenindione, sulfisoxazole, sulfadiazine, temazepam, sulfamerazine, and trioxsalen, and
said at least one hydrophilic pharmaceutically active substance comprises a compound selected from the group consisting of 17β-estradiol, acyclovir, estriol, raloxifene, pravastatin, atenolol, aminoglycosides, polysaccharide, cyclodextrins, and chitosan.

3. The 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.

4. The 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. The device according to claim 1 , wherein the polyurethane composition is made by a process wherein the catalyst stannous octoate is used.

6. The device according to claim 1 , further comprising antioxidants.

7. The 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 the patient's body.

9. The device according to claim 1 , wherein the percentage of the silicone soft segment is up to 40 weight % of the total weight of the polyurethane copolymer.

10. The device according to claim 1 , wherein the percentage of the silicone soft segment is up to 20 weight % of the total weight of the polyurethane copolymer.

Assignees

• Dsm Ip Assets Bv
• Dsm Ip Assets Bv

Inventors

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

Classifications

• A61K31/675

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

• C08G18/73

  acyclic · 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

• A61K31/341

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