Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.


  1. Advanced Patent Search
Publication numberUS3920805 A
Publication typeGrant
Publication dateNov 18, 1975
Filing dateDec 17, 1973
Priority dateDec 9, 1971
Publication numberUS 3920805 A, US 3920805A, US-A-3920805, US3920805 A, US3920805A
InventorsRoseman Theodore J
Original AssigneeUpjohn Co
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Pharmaceutical devices and method
US 3920805 A
Abstract  available in
Previous page
Next page
Claims  available in
Description  (OCR text may contain errors)

United States Patent [191 Roseman Nov. 18, 1975 PHARMACEUTICAL DEVICES AND METHOD [75] Inventor:- Theodore J. Roseman, Portage,


[731 Assignee: The Upjohn Company, Kalamazoo,


[22] Filed: Dec. 17, 1973 [21] Appl. No.: 425,600

Related US. Application Data [63] Continuation of Ser. No. 206,437, Dec. 9, 1971,

3,566,874 3/1971 Shepherd et a1 128/349 OTHER PUBLICATIONS Mishell et al. Am. J. Obstet. Gynec. 107: 100-107 May 1, 1970, Contraception by Means of a Silastic Vaginal Ring lmpregnated with medroxyprogesterone Acetate.

Mishell et al. Fertility & Sterility 21199-103 Feb. 1970, Contraceptive Effect of Varying Dosages of Progestogen in Silastic Vaginal Rings.

Barkor Candd. Vet. J1. 7/912189-192 Sept. 1966, Progestin Impregnated Vaginal Pessaries for Estrous Cycle Synchronization in Sheep.

Primary Examiner-Shep K. Rose Attorney, Agent, or Firm-John J. Killinger; Roman Saliwanchik [57] ABSTRACT A solid pharmaceutical device formed of a nontoxic resilient polymer and medication releasable therefrom during residence in a living mammal. The device has a nonmedicated core of the polymer encircled by a medicated coating of the polymer. Reduced content of diffusible medication is achieved.

2 Claims, 8 Drawing Figures US. Patent Nov. 18, 1975 Sheet 1 of3 3,920,805

figure f/yure 3 U8. Patent Nov. 18, 1975 Sheet 2 of 3" 3,920,805

figure 5 figure 4 figure 6 4 RATE (mg./day ring) U.S. Patent Nov. 18, 1975 Sheet3 of3 3,920,805

il O o o l l I l l l l l J 4 a 12 1e 20 TIME (Days) In virro release rates of medraxypragesre'rane acetate from dimethylpolysiloxane rings.

0 Ring MM /00 mg. owe/sea f/zroz/g/muf, .05 1'0 Figures 6 0/20 7.

O fP/ng w/ffi 6/.96 mg. 075 arsed /'/2 outer coo/mg,

0s m F/gz/res 4 and PHARMACEUTICAL DEVICES AND METHOD This application is a continuation of Ser. No. 206,437, filed Dec. 9, 1971, now abandoned.

BACKGROUND OF THE INVENTION This invention arises in the field of medicated devices for placement or implantation in a living body. Such devices release the medication whilst the carrier substance of which the device is formed is not absorbed but merely acts as a matrix and is itself substantially unchanged during the time of residence in the body. This is in contrast to release of a medication by solution of the substance used to transport the medication as in an oral or implanted tablet or an aqueous solution or like medicament.

It is known that a rubbery silicone-type polymer provides a nonabsorbed carrier matrix from which medication will diffuse into a surrounding liquid; Dziuk and Cook, Passage of Steroids through Silicone Rubber, Endocrinology, 781208 (1966). US. Pat. No. 3,279,996 discloses the use of a polysiloxane rubber as an implantation agent for devices dispensing diffusible medication. US. Pat. No. 3,545,439 discloses a ring device for body placement containing a resilient polymeric substance such as a polysiloxane or polyurethrane elastomer, also nylon, dacron, teflon, polyethylene. A wide variety of medication for dispensing via the polymeric devices is disclosed in US. Pat. No. 3,279,996 and US. Pat. No. 3,545,439. Other relevant descriptions and disclosures are found in several publications, viz., Folkman and Edmonds, Circulation Research 101632 (1962); Folkman and Long, J. Surg. Res. 432139 (1964) and Powers, J. Parasitology 512153 (Apr. 1965).

Widely varying types of polymeric material are suitable in providing compatible, nontoxic and nonabsorbable properties, for example organopolysiloxane of the linear type converted to rubber by heat curing (vulcanization). These linear organopolysiloxanes are known as the conventional type, for example dimethylpolysiloxane. Likewise suitable are those known as the RTV type which are converted to the rubbery state at room temperature in the presence of a catalyst. US. Pat. No. 3,279,996 describes various conventional silicone rubbers which may or may not contain fillers, such as silica, to enhance tensile strength and the other physical properties of the cured rubber. This patent also describes commercially available RTV silicone rubbers.

Other patent literature shows the preparation of conventional silicone rubbers, illustratively US. Patents Warwick, US. Pat. No. 2,504,137; Konkle et al., US. Pat. No. 2,890,188; and other patents set forth in the US. Pat. to Long et al., No. 3,279,966. Other suitable nontoxic, nonabsorbable, compatible, drugpermeable polymeric materials are, for example, nylon, a polyamide resin made by polymerization of the hexamethylenediamine salt of adipic acid; dacron, a synthetic fiber made by E. I. DuPont de Nemours and Co. from teraphthalic acid and ethylene glycol; teflon, a tetrafluoroethylene polymer manufactured by E. I. DuPont de Nemours and Co.; polyurethane elastomer prepared according to known methods from polyisocyanate and polyhydroxyl material. The polyhydroxyl materials, for example polyesters, polyethers and the like, are reacted with isocyanates to yield rubberlike products for use as rnillable gums or in casting systems or as thermo processable resins. See US. Pat. Nos. 2,871,218 and 2 3,015,650. Another exemplary polymer is polyethylene, prepared by polymerization of ethylene, usually prepared from natural gas or the cracking of crude oil. Modern Plastics Encyclopedia for 1968, Sept. 1967, Vol. 45, No. la, McGrawJ-Iill, New York, N.Y., describes the preparation of the aforesaid suitable plastic materials, especially in reference to their molding qualities, compression molding temperatures, and compression molding pressures. Details on the aforesaid polymers are given in the plastic properties chart of the aforesaid Encyclopedia, pages 29 through 46, inclusive. In reference to the non-absorbability and nontoxic nature of the aforesaid polymeric material, US. Pat. No. 3,272,204 refers to the use of vinyon N, nylon, orlon, dacron, teflon, and the like as nonabsorbably, reinforcing strands for the preparation of prostheses. Such strands have the advantage that they do not become a part of the body tissues. So it is with the improved device of the present invention, which is particularly advantageous because of its ready insertion and ready retention but does not become or form any part of the tissue of the mammal utilizing the device, for example human and animal, such as dogs, cattle, and horses. In this respect, the present device, with its medication contained therein for continued medication as desired, is greatly superior due to economy of medication.

The aforesaid polymeric substances are compatible with a body environment in which they are used in that no breakdown or absorption of the polymer occurs nor is there any deleterious effect on the body environment, only the medication being absorbed for the desired local or systemic effects.

BRIEF SUMMARY OF THE INVENTION This invention relates to an improved pharmaceutical device formed of compatible polymeric substance and containing therein difiusible medication. The device is suited for placement within a living mammalian body, for example man and valuable warm blooded animals such as dogs, sheep, cattle and horses. The medication diffuses through'the polymeric device, is absorbed by the surrounding body fluids and exerts its desired effect as long as the device is retained within the body. The polymeric substance is compatible and nonabsorbable being removable in total unchanged when it is desired to terminate treatment with the medication. Thus, continuing treatment is provided during the bodys retention of the device and treatment is terminated upon removal. The present invention provides improvement by reducing the amount of medication required in the device by locating the medication in an outer coating of polymeric material which encircles a core of nonmedicated polymeric material.

An in vitro method of test utilizes polymeric material, e.g., polysiloxane tubing which is loaded with the par ticular drug and plugged at the ends with polysiloxane cement. After allowing about 48 hours for setting or curing, the filled link of tubing is placed in, for example, 50 ml. of normal saline in a suitable container and shaken at approximately body temperature for about 24 hours. Spectroscopic analysis of the liquid, for example by the isonicotinic hydrazide method for medroxyprogesterone acetate, shows that the drug is capable of permeating through the silastic into the saline material, in which it can be demonstrated by the in vitra test. For in vivo testing, placement of a suitable size device containing a known amount of medicaments, e. g., medroxyprogesterone acetate in a polysi- 3 loxane, molded-rubber ring and retention in the vagina of the monkey for a period of about 2 months shows that the initial content of the drug is appreciably reduced.

An additional, in vivo, technique for determining the suitability of the polymeric material for use in the preparation of the inventive device is as follows: 150 mg. of medroxyprogesterone acetate is well mixed with 615 mg. of polysiloxane elastomer 382 (Dow Corning Company) to prepare resilient containers approximately 4 cm. long and 0.48 cm. in diameter. Different dosages of the drug are obtained by cutting the required length of the material. The material is sterilized and can be inserted subcutaneously into the scapular region of normally cycling female rats. Daily records of vaginal cytology, which reflect the release of the medroxprogesterone acetate, are made for periods of 2 to 6 weeks at dosages of 18.75 mg. for 6 weeks in four animals, 37.5 mg. for 2 weeks in four animals, and 56.25 mg. for 2 weeks in four animals. Cycling is prevented in the otherwise normally cycling female rats. This shows that the active medicament is released by diffusion through the drug-permeable polymer and exerts its physiological efi'ect via the vaginal tract. In addition to the in vivo data in the rats, it was found by measuring the final content of the medicament in the silastic material that average total release of 4.4 mg, mg. and 5.2 mg. occurred from elastomeric carrier material of 0.5, 1.0 and 1.5 cm. in size, respectively.

The amount of medication in each of the devices is that sufficient for bringing about the desired physiologic effect, for example, the amount sufficient for controlling fertility. Given in ranges of active ingredients, suitable amounts for individual drugs in the device are as follows: digitoxin, 5 to 50 mg; triiodothyronine, l to mg.; isoproterenol, 100 mg. to 2 Gm.; atropine, 10 to 250 mg.; histamine, l to 10 mg.; nitrogen mustard, 50 mg. to 2 Gm.; vitamin B 0.5 to 100 mg.; pyrimethamine, 50 mg. to l Gm.; estradiol, 0.5 to 100 mg; progesterone, 50 mg. to 2 Gm.; androstenedione, 50 mg. to 2 Gm.; testosterone, 50 mg. to 2 Gm.; cortisol, 100 mg. to 2.5 Gm.; medroxyprogesterone acetate, 50 mg. to 2 Gm.; melengestrol acetate, 50 mg. to 2 Gm.; chlormadinone, 50 mg. to 2 Gm. The amount of any additive medication, for example locally effective antimicrobial agent, is calculated on the basis of the known amounts useful in similar vaginal applications. Other principal active medicaments are, for example, antiulcer and antisecretory agents, for example methscopolamine, 75 mg. to 2 Gm.; anticoagulant, for example diphenadione, 75 mg. to l Gm.; hypocholesteremic agent, for example 3-methyl-5-isoxazole carboxylic acid, 200 mg. to 2 Gm.; anti-tumor drugs, for example cytarabine, 100 mg. to 3 Gm.; appetite depressant, for example D- amphetamine, 100 mg. to 2 Gm.; tranquilizers and sedatives, thiothixene and haloperidol, 50 mg. to 2 Gm.; hypoglycemic agent, 1 p-2-(5-chloro-o-anisamido) ethyl phenyl sulfonyl-3-cyclohexylurea, 100 mg. to 2.5 Gm.; hypotensive agent, mecamylamine, 100 mg. to 1.5 Gm.; antibacterial and antimalarial agents, 7- deoxy-7(S)-chlorolincomycin, 2 to 7 Gm., N-demethyl lincomycin, 2 to 7 Gm., 4'-pentyl-N-demethyl-7(S)- chlorolincomycin, l to 5 Gm.; antihypertensive agent, for example angiotensin amide, 100 mg. to 2 Gm.; glucocorticoid, for example dexamethasone, 10 to 250 mg.; prostaglandins, for example PGE PGE PGA, as antiulcer and antisecretory agents and for inhibition of blood platelet-stickiness, 0.5 to 10 mg.; PGF for control of fertility, 0.5 20 mg. The aforesaid amounts are ranges of active ingredients to be included in the device, the exact amount depending upon the age, condition of the patient, and the particular effect desired. These amounts are calculated to provide predetermined daily release dosages as follows: for the cardiac stimulant digitoxin, 0.1 to 0.2 mg; for the metabolic stimulant triiodothyronine, 5 to mcg.; for the bronchodilator isoproterenol, 5 to 30 mg; for the antianemia agent vitamin B 10 to 300 mcg.; for the antimalarial pyrimethamine, l to 5 mg; for the estrogen estradiol, l to 500 mcg.; for the progestogen progesterone, 0.1 to 20 mg; for the androgens androstenedione and testosterone, 0.1 to 10 mg.; for the glucocorticoid cortisol, 5.0 to 50 mg; for the progestogens medroxyprogesterone acetate, melengestrol acetate, and chlormadinone, 0.01 to 10 mg.; for the methscopolamine, 3 to 20 mg; for the diphenadione, 3 to 5 mg; for the 3-methyl- 5-isoxazole carboxylic acid, 10 to 30 mg; for the antitumor drug cytarabine, 60 to 300 mg.; for D-amphetamine, 5 to 30 mg; for thiothixene, 2 to 30 mg.; for haloperidol, 2 to 15 mg.; for the hypoglycemic cyclohexylurea compound, 5 to 50 mg; for the hypotensive mecamylamine, 2 to 10 mg; for the antibacterial, antimalarial lincomycin agents, 250 to 500 mg, 250 to 500 mg. and to 300 mg., respectively; for the angiotensin amide, 0.7 to 30 mg; for the dexamethasone, 0.2 to 2 mg; and for the prostaglandins, l to 100 mcg.

Depending upon the anatomyl the anatomy particular species involved, the improved ring device will vary in size, for example in the case of the human from about 60 mm. diameter to about 80 mm. diameter, these dimensions being overall dimensions; the diameter of the actual ring itself will be in the neighborhood of about 5 to 10 mm. In the case where an endless helical spring or flat spring structure is used for additional tensing property, the diameter of this metallic part of the ring will vary with that of the device itself. Overall dimensions of the improved medicated ring for use in other species are approximately as follows: for sheep and swine, 20 to 65 mm.; for dogs, 5 to 50 mm.; for cats, 5 to 30 mm.; for cattle, 50 to 100 mm.; and for horses, 50 to mm. These dimensions are overall dimensions. As will be apparent, the actual diameter of the ring itself varies with the overall size and with the particular species. Suitably the annular devices may incorporate a tab for assistance in removal. The polymeric materials are, as disclosed in the aforesaid Modern Plastics Encylopedia, those that are suitable for molding in manners known to those familiar with this art. Those polymeric materials, for instance the organopolysiloxanes, which are in a liquid state or paste state, can be directly mixed with the drug, for example melengestrol acetate or medroxyprogesterone acetate, and the semifiuid material placed into the mold for compression molding with the addition of a catalyst, for example stannous octoate. In case the device is to contain a spring structure for tension properties, this is usually centered in the semifluid material while it is in the mold and thereafter covered by additional drug-containing polymeric material for the compression moldmg.

BRIEF DESCRIPTION OF THE DRAYVING FIG. 1 is a perspective view of a tangible embodiment of the concept of the invention.

FIG. 2 is a sectional view taken along the line II II in FIG. 1.

FIG. 3 is a perspective view of an alternate embodiment.

FIG. 4 is a photographic cross-sectional view of a ring emodirnent with central core and outer coating.

FIG. 5 is a photographic cross-sectional view of the ring of FIG. 4 after three weeks leaching in distilled water.

FIG. 6 is a photographic cross-sectional view of a conventional ring device without central core and outer coating.

FIG. 7 is a photographic cross-sectional view of the ring of FIG. 6 after three weeks leaching in distilled water.

FIG. 8 is a graphic representation of release rates of medication.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS As set forth in FIGS. 1 and 2 which portray together a preferred embodiment of the invention a device of the invention takes the form of a resilient individual ring 10 for vaginal placement with a centered nonmedicated polymeric core 11 and a polymeric coating 12 containing the medication 13. To avoid too close proximity of the edge of the core to the edge of the ring, a three step molding process is used to provide a precisely centered core as in FIG. 2.

First Step. Add 0.36% by weight of stannous octoate to q.s. dimethylpolysiloxane (Dow Corning Silastic 382). Mix well. Place the mix into two halves of a mold to provide a centered polymeric core of 62.2 mm. outside diameter and 3.6 mm. cross-sectional diameter. Tighten the mold with wing nut. Cure.

Second Step. Place the cored nonmedicated polymeric core into one-half of its mold. Fill one-ha1f of an outer mold (65 mm. outside diameter and 6.4 mm. cross-sectional diameter) with medicated polymeric mixture containing 1.386% medroxyprogesterone acetate and 0.36% stannous octoate. Place the filled one-half over the core of the first step and cure.

Third Step. After the mold of the second step is cured,

the other half of the outer mold is filled with the medicated polymeric mixture. This half plus the cured half of the second step are bonded together and the whole is cured again.

The average weight of the outer coating of 10 rings is 4.49 Gm. with an average core weight of 2.17 Gm. At

6 61.96 mg. As shown in FIG. 8 the release rates are substantially the same despite the lesser overall amount of medication.

Under in vitro and in vivo conditions a zone of depletion results as medication diffuses from the polymer. This zone is void of solid medication particles. In order for the medication to be released from the core ring at the same rate as a completely filled ring, the zone of depletion over the given time interval must not be greater than the distance from the surface of the device to the surface of the core. The dimensions of the placebo core are designed to meet this requirement.

FIGS. 4 and 5 show the zones which result upon use of the ring of FIG 1. In FIG. 4 there is the medication filled outer coating 13 and the inner nonmedicated core 11. After use as shown in FIG. 5 there is a zone of depletion 14 as the medication diffuses out of the coating 12. In the conventionally filled ring of FIG. 6 there is the medication containing area 13 which remains the same in FIG. 7 except for the zone of depletion 14. The zones of depletion 14 in FIG. 5 and also 14 in FIG. 7 are the same.

FIG. 3' is a perspective view of an alternate embodiment of the inventive concept. It is a solid cylinder for implantation. For example, in the ear region of an animal such as a cow.

It will be apparent to those of skill in the revelant art that there are obvious structural variants by means of which the inventive concept can be practiced. Included therein but not limited thereto are a plurality of outer medicated coatings of different concentrations of the same medicament or coatings of different medicaments useful in combination. Also spring or equivalent means can be included in the core to provide tension.

I claim:

1. A solid pharmaceutical device formed as a vaginal ring of a nontoxic resilient medication diffusing organopolysiloxane polymer and an effective vaginal dosage amount of a medication diffusible therein which releases said medication during residence in the vaginal cavity of a living mammal consisting essentially of, in

combination, a nonmedicated central core of said poly-' mer and an encircling finite thickness of a medicated coating of said polymer.

2. The device of claim 1 which is formed of dimethylpolysiloxane with a centered metallic, endless, helical or flat tensioning spring molded in the nonmedicated central core and the diffusible medication is medroxyprogesterone acetate.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3312215 *Aug 2, 1963Apr 4, 1967Silber Max NUterocervical cannula
US3545349 *Aug 1, 1968Dec 8, 1970Henrich GottfriedSelf-propelling paving machine
US3566874 *Aug 13, 1968Mar 2, 1971Nat Patent Dev CorpCatheter
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4012496 *Oct 17, 1975Mar 15, 1977Schering AktiengesellschaftVaginal ring
US4012497 *Sep 23, 1975Mar 15, 1977Schering AktiengesellschaftDrug excipient of silicone rubber
US4155991 *Mar 3, 1977May 22, 1979Schering AktiengesellschaftVaginal ring
US4191741 *Sep 22, 1978Mar 4, 1980Eli Lilly And CompanyRemovable drug implant
US4215691 *Oct 11, 1978Aug 5, 1980Alza CorporationVaginal contraceptive system made from block copolymer
US4237885 *Oct 23, 1978Dec 9, 1980Alza CorporationDelivery system with mated members for storing and releasing a plurality of beneficial agents
US4264575 *Apr 8, 1980Apr 28, 1981Eli Lilly And CompanyContraceptive methods and compositions
US4264576 *Apr 8, 1980Apr 28, 1981Eli Lilly And CompanyContraceptive methods and compositions
US4264577 *Apr 8, 1980Apr 28, 1981Eli Lilly And CompanyContraceptive methods and compositions
US4264578 *Apr 8, 1980Apr 28, 1981Eli Lilly And CompanyContraceptive methods and compositions
US4292965 *Dec 29, 1978Oct 6, 1981The Population Council, Inc.Intravaginal ring
US4402695 *Mar 30, 1981Sep 6, 1983Alza CorporationDevice for delivering agent in vagina
US4411658 *Feb 17, 1981Oct 25, 1983Roussel UclafDevice for administering
US4469671 *Feb 22, 1983Sep 4, 1984Eli Lilly And CompanyContraceptive device
US4589880 *Jul 14, 1983May 20, 1986Southern Research InstituteDisposable spermicide-releasing diaphragm
US4871543 *Jun 12, 1987Oct 3, 1989Aktiebolaget LeoIntravaginal devices
US4888074 *Jul 21, 1988Dec 19, 1989Dow Corning France S.A.Therapeutic rings
US4961931 *Sep 9, 1988Oct 9, 1990Alza CorporationMethod for the management of hyperplasia
US5224493 *Jan 30, 1991Jul 6, 1993Cadco CorporationContraceptive intracervical device and novel nonsystemic agents for the prevention of conception and disease
US5398698 *Nov 15, 1989Mar 21, 1995Hoechst AktiengesellschaftProcess for preparing an intravaginal application system
US5660187 *Dec 29, 1994Aug 26, 1997Hoechst AktiengesellshaftProcess for preparing an intravaginal application system
US5694947 *Jun 15, 1994Dec 9, 1997Leiras OyIntravaginal delivery system
US5972372 *May 2, 1997Oct 26, 1999The Population Council, Inc.Intravaginal rings with insertable drug-containing core
US6126958 *May 21, 1999Oct 3, 2000The Population Council, Inc.Intravaginal rings with insertable drug-containing core
US6207717 *Jan 12, 1999Mar 27, 2001Dow Corning CorporationEntrapment of vitamins with an elastomeric silicone polyether
US6394094 *May 3, 1999May 28, 2002Enhance Pharmaceuticals, Inc.Method for injection molding manufacture of controlled release devices
US6416780May 7, 1998Jul 9, 2002Galen (Chemicals) LimitedIntravaginal drug delivery devices for the administration of testosterone and testosterone precursors
US6423039Apr 30, 1997Jul 23, 2002InteragSynchronizing of animal oestrus and intra vaginal devices useful therein
US6663608Oct 11, 2001Dec 16, 2003InteragSynchronizing of animal oestrus and intra vaginal devices useful therein
US6770288Feb 9, 1999Aug 3, 2004Pfizer Products Inc.Drug delivery system
US7829112May 22, 2008Nov 9, 2010The General Hospital CorporationMethods and devices for the sustained release of multiple drugs
US7833545Apr 29, 2004Nov 16, 2010The General Hospital CorporationMethods and devices for the sustained release of multiple drugs
US7838024May 22, 2008Nov 23, 2010The General Hospital CorporationMethods and devices for the sustained release of multiple drugs
US7883718May 22, 2008Feb 8, 2011The General Hospital CorporationMethods and devices for the sustained release of multiple drugs
US7910126Mar 20, 2007Mar 22, 2011Teva Women's Health, Inc.Flexible, compressed intravaginal rings, methods of making and using the same, and apparatus for making the same
US8217219Dec 29, 2003Jul 10, 2012Kimberly-Clark Worldwide, Inc.Anatomically conforming vaginal insert
US8323679Jan 5, 2011Dec 4, 2012Teva Women's Health, Inc.Flexible, compressed intravaginal rings, methods of making and using the same, and apparatus for making the same
US8399013 *Sep 8, 2004Mar 19, 2013Poly-Med, Inc.Partially absorbable fiber-reinforced composites for controlled drug delivery
US8404272 *Jun 3, 2004Mar 26, 2013Poly-Med, Inc.Fiber-reinforced composite rings for intravaginal controlled drug delivery
US8419793 *Mar 12, 2010Apr 16, 2013Mentor Worldwide LlcCoating with antimicrobial agents
US8420153 *Sep 19, 2008Apr 16, 2013Mentor Worldwide LlcCoating with antimicrobial agents
US8506543Jun 11, 2012Aug 13, 2013Kimberly-Clark Worldwide, Inc.Anatomically conforming vaginal insert
US8580294Oct 19, 2011Nov 12, 2013International Partnership For MicrobicidesPlatinum-catalyzed intravaginal rings
US8715712Nov 28, 2012May 6, 2014Forsight Vision5, Inc.Ocular insert apparatus and methods
US8939948Sep 14, 2012Jan 27, 2015Forsight Vision5, Inc.Ocular insert apparatus and methods
US20040265355 *Jun 3, 2004Dec 30, 2004Shalaby Shalaby W.Composite absorbable/biodegradable rings for controlled drug delivery
US20050053639 *Sep 8, 2004Mar 10, 2005Shalaby Shalaby WPartially absorbable fiber-reinforced composites for controlled drug delivery
US20130195950 *Mar 13, 2013Aug 1, 2013Titan Pharmaceuticals, Inc.Heterogeneous implantable devices for drug delivery
DE3040978A1 *Oct 28, 1980May 27, 1982Schering AgVaginalring
EP0025699A1 *Sep 11, 1980Mar 25, 1981Eli Lilly And CompanyDevice for drug delivery to ruminants
EP0253109A1 *May 27, 1987Jan 20, 1988Kabi Pharmacia ABIntravaginal device and method of preparing the same
EP0330786A1 *Dec 30, 1988Sep 6, 1989Masao IgarashiTopical drug delivery systems containing danazol
EP1061987A1 *Feb 9, 1999Dec 27, 2000Graham Francois DuirsDrug delivery system
EP2246062A1Jul 19, 2006Nov 3, 2010The Population Council, Inc.Methods and compositions for emergency contraception using endothelin receptor antagonists
EP2641602A1Mar 23, 2012Sep 25, 2013PregLem S.A.Method for treating gynecological diseases
WO1995000199A1 *Jun 15, 1994Jan 5, 1995Matti LehtinenIntravaginal delivery system
WO1995009641A1 *Oct 3, 1994Apr 13, 1995Lectin Biopharma IncUsing lectins for contraception, prophylaxis and therapy
WO1997040776A1 *Apr 30, 1997Nov 6, 1997Craig Robert BuntSynchronising of animal oestrus and intra vaginal devices useful therein
WO1998050016A2 *May 7, 1998Nov 12, 1998Galen Chemicals LtdIntravaginal drug delivery devices for the administration of testosterone and testosterone precursors
WO1999056934A1May 3, 1999Nov 11, 1999John F ClineMethod for injection molding manufacture of controlled release devices
WO2011163358A2 *Jun 22, 2011Dec 29, 2011Anu MahashabdeIntravaginal devices comprising anticholinergic agents, and methods of making thereof
WO2013140372A1Mar 22, 2013Sep 26, 2013Preglem SaMethod for treating gynecological diseases
WO2014167510A2Apr 9, 2014Oct 16, 2014Preglem SaProgesteron receptor modulators for use in the therapy of uterine fibroids
U.S. Classification424/432, 128/832
International ClassificationA61M31/00, A61K9/20, A61D7/00, A61K9/00
Cooperative ClassificationA61K9/0036, A61D7/00, A61M31/002, A61K9/2036
European ClassificationA61M31/00D, A61K9/20H6D2, A61K9/00M8B, A61D7/00