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Publication numberUS3699951 A
Publication typeGrant
Publication dateOct 24, 1972
Filing dateJan 19, 1970
Priority dateJan 19, 1970
Publication numberUS 3699951 A, US 3699951A, US-A-3699951, US3699951 A, US3699951A
InventorsZaffaroni Alejandro
Original AssigneeAlza Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Device for suppressing fertility
US 3699951 A
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Description  (OCR text may contain errors)

United States Patent Zaffaroni [54] DEVICE FOR SUPPRESSING FERTILITY [72] Inventor: Alejandro Zaffaroni, Atherton,

Calif.

[73] Assignee: ALZA Corporation [22] Filed: Jan. 19, 1970 [21] Appl.No.: 3,852

[52] U.S.Cl ..128/130, 424/16 [51] Int. Cl. ..A41b 3/12 [58] Field ofSearch ..128/127131,215, 128/260, 285

[56] References Cited UNITED STATES PATENTS 3,312,215 4/1967 Silber ..128/131 1,982,001 11/1934 Haas ..128/130 I 2,896,614 7/1959 Schmitt etal ..l28/131 FOREIGN PATENTS OR APPLICATIONS 981,389 1/1965 Great Britain ..l28/130 51 Oct. 24, 1972 3/1962 Great Britain 1 28/130 OTHER PUBLICATIONS American Journal Obstet Gynec, May 1, 1967, pages 126 and 127.

[57] ABSTRACT Fertility suppression in a female mammal is achieved with a device for insertion and retention in the uterus in the form of a flexible, resilient body of polymeric material having an elastic memory. The body has an ellipsoidal shape and a fluted-surface. When inserted into the uterine cavity in a compacted state, the body assumes an ellipsoidal configuration. Preferably, the device contains an anti-fertility agent, most preferably progesterone, and is permeable to passage of the antifertility agent at a low rate. Upon insertion in the uterus, the device releases a fertility suppressing amount of the anti-fertility agent to the uterus.

4 Claims, 10 Drawing Figures PATENTED 24 I973 3 699,951

sum 1 0F 2 l INVENTOR. Alejandro Zaffaroni fww,

Attorney PATENTEU 0m 24 I972 SHEET 2 OF 2 DEVICE FORSUPPRESSING FERTILITY BACKGROUND OF THE INVENTION This invention relates to an anti-fertility device, and more especially, to an anti-fertility device for insertion and retention in the uterus.

Intrauterine contraceptive devices have become an increasingly popular method of birth control. Widely used devices include the Lippes Loop, Margulies Spiral, Birnberg Bow, and Grafenberg Ring. In general, these devices are formed of thin rods or tubes of polymeric material bent to a shape which will abut against the walls of the uterus. Forces exerted by uterine contraction frequently expel these intrauterine devices. And the constant contact of the uterine walls with the bent rod-like configuration of such intrauterine devices has caused irritation, erosion and even puncture of the uterine walls.

To reduce uterine contractility and hopefully to overcome these disadvantages, it has been proposed to incorporate progestational agents into intrauterine devices. See Doyle et al., Amer. J. Obstet. Gynecol., 101, 564-568 (1968). Other investigators have incorporated progestational agents in these intrauterine devices with the aim of controlling fertility by the hormonal effect from the gradual release of the progestational agent. See Scommegna et al., Intrauterine Administration of Progesterone by a Slow Releasing Device, presented at annual meeting of the American Fertility Society, April 1969. While there are indications that problems of expulsion, erosion, and irritation may be minimized by use of a progestational agent, these problems are inherent in the conventional bent rod configuration of the intrauterine device and have not been overcome by the incorporation of such chemical agents.

More Recently, various inflatable intrauterine contraceptive devices have been proposed. These, however, have substantial inherent disadvantages and dangers which have prevented their acceptance by the medical community. The theory of these devices is that they will be inserted into the uterus in a collapsed condition and, when in place, inflated by means of air or liquid under pressure. Inflation of such devices creates substantial dangers of uterine rupture unless done with the most extreme care. Moreover, there is a serious risk of infection unless the air or liquid is highly sterile.

SUMMARY OF THE INVENTION Accordingly, it is an object of this invention to provide an improved intrauterine birth control device which overcomes problems inherent in related devices previously proposed.

Another object of this invention is to provide an intrauterine device of improved shape which is non-irritating to the uterus, does not cause erosion or perforation of the uterine walls, can be easily inserted, and will remain in place for long periods of time.

Still another object of this invention is to provide an intrauterine contraceptive device of improved configuration containing and gradually releasing to the uterus an anti-fertility agent.

In attaining these objects, one feature of this invention resides in an intrauterine device comprised of a flexible, resilient body of polymeric material having an elastic memory. The body has an ellipsoidal shape and a fluted surface. When inserted into the uterine cavity in a compacted state, the body will assume an ellipsoidal configuration and resist expulsion.

A further feature of this invention resides in an intrauterine device for suppressing fertility, as described above, containing an anti-fertility agent and being permeable to passage of the anti-fertility agent so that when inserted in the uterine cavity of a female mammal the body will release a fertility suppressing amount of the anti-fertility agent to the uterus over a prolonged period of time.

Other objects, features and advantages of this invention will become more apparent from the following description and from the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings:

FIG. 1 is a frontal section through the uterus showing one embodiment of the intrauterine contraceptive device placed in the uterine cavity;

FIG. 2 is an end view of the intrauterine device of FIG. 1;

FIG. 3 is a side view, partially in cross-section, of the intrauterine device of FIG. 1 within an insertion device;

FIG. 4 is a side view, partially in cross-section, of the intrauterine device of FIG. 1 partially ejected from an insertion device;

FIG. 5 is an end view of another embodiment of the intrauterine device of the invention;

FIG. 6 is a side view of the intrauterine device of FIG. 5;

FIG. 7 is a side view of the intrauterine device of FIG. 5 partially ejected from an insertion device;

FIG. 8 is an end view of still another embodiment of the intrauterine device of the invention;

FIG. 9 is a side view of the intrauterine device of FIG. 8; and

FIG. 10 is a side view of the intrauterine device of FIG. 8 partially ejected from an insertion device.

DETAILED DESCRIPTION OF THE INVENTION In accordance with this invention, there is provided a device for suppressing fertility having shape and physical characteristics compatible with long-term retention in the uterus of a female mammal without undesirable side effects.

As illustrated in FIGS. 1 and 2, the device 10 of the invention is adapted for placement in a uterus generally defined by side walls 11 and top wall 12. Device 10 is an ellipsoidal body having a central core 13 and a fluted surface, defined by multiple projections 14 running longitudinally of the body. As used, herein, an ellipsoidal body need not be a true ellipsoid but includes any rounded body having no sharp edges or points and not necessarily of symmetrical configuration. It includes spheres, pear-shapes, egg-shapes, etc. In the preferred embodiment of the invention illustrated in FIG. 1, the device is tapered toward its lower end and therefore has a larger cross-sectional area toward its top 15 than toward its bottom 16.

Intrauterine device of the invention is formed of a flexible, resilient polymeric material having an elastic memory. It can be compacted or folded about its longitudinal axis and inserted in the uterine cavity in the compacted state. Due to the elastic memory of the polymeric material from which it is formed, the intrauterine device will assume its ellipsoidal configuration upon placement in the uterus.

Thus, as illustrated in FIG. 3, device can be placed in a compacted or folded configuration within a suitable cylindrical insertion insertion device 17 having plunger 18. Front portion 19 of insertion device 17 is placed within the uterine cavity and plunger 18 moved forward expelling device 10 into the uterine cavity. As it is expelled from insertion device 17, device 10 unfurls to assume its ellipsoidal configuration, as illustrated in FIG. 4.

Because of its bulbous fluted shape, the device of the invention is well adapted for comfortable long-term retention in the uterus. When force is applied to the device by uterine contractions, the device absorbs the force and yields, rather than reacting against the uterine walls as takes place with a conventional intrauterine device formed from rods or tubes. While conventional intrauterine devices have sharp or hard edges and surfaces which can erode and even perforate the uterine walls, the flexible, resilient ellipsoidal uterine device of the invention has a physiologic shape well suited to its role.

FIGS. 5, 6, and 7 illustrate another embodiment of the intrauterine device 10 of the invention wherein the projections or ridges 14 are disposed helically about the longitudinal axis of the ellipsoidal body. Device 10 can be compacted by rolling or folding projections 14 about the longitudinal axis. As best shown in FIG. 7, when expelled within the uterine cavity (not shown) form a suitable insertion device 17, projections 14 resume their helical disposition and the device again assumes its ellipsoidal shape. In this manner, the intrauterine device can be easily inserted in place. Projections 14 are formed of flexible resilient materials, allowing the device to comfortably remain within the uterine cavity for long periods of time.

Still a further embodiment of the intrauterine device 10 is illustrated in FIGS. 8, 9, and 10. As best shown in FlG. 9, device 10 can have projections 14 arranged horizontally about its longitudinal axis. Varying numbers of tiers of such projections can be present. To compact device 10 for insertion, projections 14 are folded downwardly. Upon placement in the uterus with an insertion device 17, projections 14 spring upwardly and the ellipsoidal shape of the body is restored. This shape too is well suited for long-term retention in the uterus.

Various flexible, resilient polymeric materials having elastic memory can be used to form the intrauterine device of the invention. Illustrative materials include polybutylmethacrylate, plasticized polyvinylchloride, plasticized nylon, silicone rubbers, and other biologically acceptable polymeric materials.

While the intrauterine device of the invention can be employed alone to provide an effective means of birth control, it is preferred to incorporate an anti-fertility agent which will be gradually released to the uterus from the device. When this is done, the device of the invention acts as a depot or drug reservoir, containing and releasing at a pre-determined rate an anti-fertility agent. Commencement and termination of action are controlled by insertion and removal of the device from the uterus. Within these time limits, the amount of antifertility agent available is controlled by release of the agent from the device at a pre-determined rate.

When the device of the invention is used as a drug reservoir, a wide variety of anti-fertility agents can be incorporated in and gradually released from the device.

Anti-fertility agent is used herein in its broadest sense as meaning any chemical agent that will suppress development of the fetus. It includes for example agents which are: spermicidal, or inhibit egg implantation, or inhibit egg mobility, or prevent ovulation, or inhibit sperm capacitation or increase thickness of the cervical mucosa.

Generally preferred for use in the invention are progestational agents. Suitable progestogens include, without limitation: progesterone; progesterone cyclopentyl enol ether; 6-dehydroretorprogesterone, l 7a-hydroxy-progesterone caproate; 6a-methyl- 1 7aacetoxyprogesterone, 6-methyl-6-dehydrol 7a-acetoxyprogesterone;6-methyll 6-methylene-6-dehydro-l 7aacetoxyprogesterone; 6-chloro-l 7a-acetoxy-6- dehydr'oprogesterone; 6,17a-dimethyl-6- dehydroprogesterone; 6, l oa-dimethyl--dehydro- 1 7aacetoxyprogesterone; l7a-acetoxyprogesterone-3- cyclopentyl enol ether; l7-ethinyltestosterone; dimethylethinyltestosterone; l9-norprogesterone, 19- nor- 1 7-ethinytestosteron e; l9-nor-l 7-ethin yltestosterone acetate; l7-ethinyl-l7B-hydroxy-5( l0)- estren-3-one; l 7-ethinyl-4-estrene-3/3 l 7B-diol diacetate; l7a-vinyl-estr- 5( lO)-en-17B-ol-3-one; 19- nor- 3-desoxy- 1 7-ethinyltestosterone; l 9-nor-3-desoxyl 7-allyltestosterone; and l7-ethinyll 9-testostero ne acetate 3-cyclopentyl enol ether.

With progestational agents lacking the desired release characteristics from the device, simple pharmacologically acceptable derivatives of the hormones can be Employed. Suitable derivatives include esters with pharmaceutically acceptable acids, such as the acetate, maleate, citrate, oxalate, succinate, caproate, benzoate, tartrate, fumarate, malate, mandelate, ascorbate, and the like; ethers, especially lower alkyl ethers; acetals, etc. These derivatives should be such as to convert to the parent progestational agent on release from the device, by enzymatic transformation, pl-l assisted hydrolysis, and the like.

Progesterone, the natural progestational agent, is the preferred anti-fertility agent for use in this invention. By locally applying progesterone to the uterus, the desired progestational activity is obtained in the uterus. Progesterone is rapidly metabolized in the uterine walls to metabolites which are progestationally inactive out side of the uterus. Thus, the situs of progestational activity is circumscribed within the uterus. Undesired systemic progestational activity is not obtained and a physiologic means of birth control is provided.

The amount of progestational agent incorporated in the device to obtain the desired fertility suppression will vary depending on the particular hormone used and the length of time the device is to remain in place. Since these devices are intended to control fertility for an extended period of time, such as three months to one year or more, there is no critical upper limit on the amount of hormone incorporated in the device. For when the capsule is removed and disposed of, it makes little difference whether any hormone remains in the device. The lower limit will depend on the activity of the progestational' agent and its capability of being released to the uterus. Thus, it is not practical to define a range for the fertility suppressing amount of progestational agent incorporated in or released from these devices. However, with devices containing progesterone and intended to remain. in place for one year, typically, from 40 to 500' milligrams of progesterone are incorporated in the devices. Such devices are designed to release progesterone at a rate of from 100 micrograms to l milligram per day. With devices containing a more highly active progestational agent, such as 6-chloro-l7a-acetoxy-6- dehydroprogesterone, and also designed for one year of use, from 10 to 100 milligrams of hormone is incorporated inthe device and the device is designed to release the hormone at a rate of between and 200 micrograms per day. For devices containing other progestational agents, the progestational agent is incorporated in and released from the device in an amount equivalent in activity to these ranges. v

In lieu of the progestational agents described above, one can incorporate in the device of this invention a locally contraceptively active metabolite of progesterone, as described in my copending patent application Ser. No. 864,174, filed Oct. 6, l969assigned to the assignee of this invention. The disclosure of that copending application is relied upon and incorporated herein by reference. I

Additionally, pregnenolone and other chemical agents that may be converted to progesterone by the endometrium can be used as the anti-fertility agent, as described in my copending patent application Ser. No. 884,305, filed Dec. 1 l, 1969, assigned to the assignee of this invention.- The disclosure of that copending application is relied upon and incorporated herein by reference.

Another class of suitable anti-fertility agents which can be used are the prostaglandins, especially prostaglandin F 01.

Still another class, of suitable anti-fertility agents is represented by cyclic AMP and its derivatives, as dis- I at least in part of a material permeable to the agent, as

by diffusion, to permit passage of the agent through the walls or body of the device at a relatively low rate. Normally, the rate of passage of the agent through the wall or body is dependent on the porosity of the wall or body or the solubility of the anti-fertility agent in the wall or body, as well as on the wall or body thickness. This means that selection of appropriate materials for fabricating the device will be dependent on the particw lar anti-fertility agent to be used. By varying the composition, porosity, and thickness of the device wall or body, the release rate per area of device can be controlled; for the wall or body of the device act as solubility membranes or diffusion control systems to regulate or meter the flow of anti-fertility agent from the device to the uterus. Thus, fertility suppressing devices of the same surface area can provide different release rates and therefore different daily dosages ofthe anti-fertility agent by varying the characteristics of the device.

Suitable devices can be formed by molding into the form of a hollow container of appropriate fluted ellipsoidal shape with the anti-fertility agent contained therein. While the device walls can be of any convenient thickness, usually they have a thickness of from 0.01 to 3 millimeters. Alternatively, the device can comprise a resilient, flexible solid or gel matrix having the anti-fertility agent distributed therethrough. This can be accomplished by adding the agent to the matrix material in liquid form and subsequently converting the matrix to a solid or gel by curing or cooling; or by immersing the solid matrix in the anti-fertility agent or a solution of the anti-fertility agent to effect diffusion of the agent into the matrix. In a further embodiment, the anti-fertility agent can be encapsulated with a material permeable to passage of the agent and the microcapsules distributed throughout the solid or gel matrix. By microencapsulating the agent, further control over the rate of release of the anti-fertility agent from the device is provided. In lieu of the above forms, the device can be a resilient, flexible polymeric foam or cellular body with the anti-fertility agent distributed throughout its cell walls. Such foams can be formed by mixing the anti-fertility agent with the monomers or prepolymer prior to foaming to form the cellular device. Although the foregoing forms of the device in which the anti-fertility agent is dispersed throughout a matrix or foam can provide good control of release rate, it is often desirable to coat the matrix or foam with a thin film of another polymer to further enhance precise control over release rate. In such case, release of anti-fertility agent from the device is determined by passageof the agent through the matrix and the film coating.

Thus, the device of the invention can take various physical forms. Anti-fertility agent is metered through the walls or body of the deviceto the uterus, with the rate of release controlled by the composition, porosity, and thickness of the walls or body of the device. In each instance, the device acts as a depot for the storage and continuous release of anti-fertility agent to the uterus.

Materials used to form this embodiment of the device are those capable of forming film walls, encapsulating coatings or matrices (solid, gel, or foam through which the anti-fertility agents can pass at a relatively low rate. In each instance, they must provide a flexible, resilient body with elastic memory. At leastthe outer surface of the device is a non-irritating polymeric material insoluble in uterine fluids. Use of soluble polymers is to be avoidedsince dissolution or erosion-of the device would effect the constancy of the anti-fertility agent release, 'as well as the ability of the device to remain in place. Fabrics, fibrous masses and the like, which merely absorb and release drugs or drug solutions in a gross and uncontrollable manner are unsuitable since predictable release of the anti-fertility methacrylic acid (as described in US. Pats. Nos. 2,976,576 and 3,220,960 and Belgian Pat. No. 701,813), modified collagen, cross-linked polyvinylalcohol, cross-linked partially hydrolyzed polyvinylacetate, and surface treated silicone rubbers (as described in US. Pat. No. 3,350,216). When the device is formed of a hydrophobic polymeric material, it can be coated with a hydrophilic material to provide a soft hydrophilic surface. Suitable hydrophilic coating materials include those hydrophilic polymers just mentioned. By using a hydrophilic coating with a hydrophobic polymeric membrane, an excellent device is obtained; for the hydrophobic material, such as silicone rubber, provides the desired anti-fertility agent metering effect while the hydrophilic coating gives desired tissue compatibility and retards absorption of lipoidal materials by the device. When plasticizers are added to the polymeric materials to further impart flexibility, various plasticizers known to the art can be employed, such as long-chain fatty amides, higher alcohols, and dioctylphthalate. v

The following examples will serve to illustrate the invention without in any way being limiting thereon.

EXAMPLE 1 Dry crystalline progesterone (300 milligrams) is mixed with hydroxyethylmethacrylate (9.9 grams; water (l.1 grams) and isopropyl percarbonate (0.2 gram). The mixture is poured into a Teflon lined mold having an ellipsoidal ridged cavity 1 inch by 1.5 inch containing 0.5 inch of a 6 inch nylon-string-and polymerized at 60C for 2 hours under a nitrogen at mosphere. After removal from the mold, the capsule is soaked-in distilled water for 48 hours to leach out residual monomer. The capsule is then coated with a flexible membrane having a thickness of 0.5 millimeter by dipping in a chloroform solution of 50-50 copolymer of n-butyl and isobutylmethacrylate. After drying, a hydrophilic coating is applied to the capsule by dipping in a prepolymer of polyhydroxyethylmethacrylate (prepared from hydroxyethylmethacrylate and 0.02 percent isopropylpercarbonate at 35C for 0.5 hour) containing 0.02 percent fresh isopropylpercarbonate; the coating is cured at 55C for 1 hour in a nitrogen atmosphere after which residual monomer is removed by soaking in distilled water for 48 hours.

The resulting flexible resilient, bulbous capsule has a soft hydrophilic surface and contains 290 milligrams of progesterone. It has the configuration illustrated in FIG. 1. When inserted in the uterus, it releases about 0.3 milligram of progesterone per day and provides an effective means of birth control for up to 1 year. Progesterone release rate from the capsule is constant over time as lipoidal materials are not absorbed by the capsule surface. The capsule is removed by pulling on the nylon string.

EXAMPLE 2 The procedure of Example 1 is repeated except that the progesterone is replaced with 50 milligrams of 6- methyl- 1 6-methylene-6-dehydro-, 1 7a -acetoxyprogesterone (melengestrol acetate). The resulting uterine capsule provides an effective means of birth control by releasing about 60 micrograms per day of the progestational agent.

- i EXAMPLE3 Dry crystalline progesterone (100 milligrams) is mixed with room temperature vulcanizing liquid polydimethylsiloxane 13.5 grams, Dow Corning medical Silastic 382 elastomer). After uniformly mixing the hormone with the unvulcanized silicone rubber, a stannous octoate (0.5 percent by weight) is added and the mixture molded in the form of a sphere having a diameter of 25 millimeters and a fluted surface. After allowing the: progesterone impregnated silicone rubber sphere to cure for 4 days at room temperature, the silicone rubber surface is rendered hydrophilic by immersing the sphere in a 6 percent solution of tetraisopropyltitanate in hexane for 5 minutes. After withdrawing the sphere from the solution, it is dried in air for 2 hours. Then the sphere is immersed for 2 hours in refluxing distilled water and finally, immersed in room temperature distilled water. The resulting uterine capsule has a hydrophilic surface and contains milligrams of progesterone. When inserted into the uterus, the capsule releases about 350 micrograms of progesterone per day to the uterine wall. It is found that the uterine capsule is non-irritating to the uterus and provides for contraception over a period of eight months after which it is removed, discarded, and replaced with an identical sphere.

EXAMPLE 4 The procedure of Example 3 is repeated except that 25 milligrams of 6-chloro-l7a -acetoxy-6- dehydroprogesterone (chlormadinone acetate) is substituted for the progesterone. The resulting spheroidal uterine capsule is effective to release about 50 micrograms of 6-chlorol 7a -acetoxy-6- dehydroprogesterone per day to the uterine wall.

EXAMPLE 5 methacrylate coating is applied as in Example 1 The resulting capsule is effective to control fertility by releasing about 325 micrograms per day of progesterone to the uterine walls.

Thus, this invention provides a reliable means of fertility suppression. A flexible, resilient intrauterine device having an ellipsoidal shape and a fluted surface is provided. The device is adapted for comfortable, long-term retention in the uterus, without the undesired toxicity and frequent ejection associated with previously proposed related devices. In addition, an anti-fertility agent can be incorporated in and gradually released from the device to the uterus, effecting fertility regulation through chemical action.

Although the forgoing has emphasized the device of the invention for fertility suppression, it will be recognized that other biologically or pharmacologically active agents can be administered to the uterus from this uterine capsule. Thus, the device can contain and release hormones such as estrogens and progestens for hormone replacement therapy; anti-inflammatory agents; anti-biotics', fungicides; muscle relaxants; and others.

While the invention has been described and illustrated with reference to certain preferred embodiments thereof, those skilled in the art will appreciate that various modifications, changes, omissions and substitutions can be made without departing from the spirit of the invention. It is intended, therefore, that the invention be limited only by the scope of the following claims.

What is claimed is: a

1. An intrauterine contraceptive device, non-irritating to the uterus and which does not cause erosion or perforation of the uterine walls, said device being adapted for comfortable long-term retention in the uterus, and which device comprises. a flexible, resilient body of polymeric material having an elastic memory, said body having a central core provided with a fluted surface and defining a bulbous ellipsoidal shape, the

said fluted surface comprising continuous projections running geometrically about an axis of the said central core and being wholly integral therewith, and the said fluted surface also being adapted to absorb force applied in any direction to the device by uterine contractions and defining the sole means by which the device is mechanically retained in proper place abutting against the walls of the uterus, whereby the said body can be inserted into the uterine cavity in compacted state and thereupon will assume the bulbous ellipsoidal configuration.

' 2. The intrauterine device of claim 1 wherein the flutes are disposed substantially longitudinally of said body.

3. The intrauterine device of claim 1 wherein the flutes are disposed substantially helically about said body.

4. The intrauterine device of claim 1, wherein the flutes are disposed substantially horizontally about said body.

Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3888975 *Dec 27, 1972Jun 10, 1975Alza CorpErodible intrauterine device
US3898986 *Dec 27, 1972Aug 12, 1975Alza CorpBiotransformable intrauterine device
US3905360 *Jul 23, 1973Sep 16, 1975Alza CorpIntrauterine device for governing the reproductive process
US3933153 *Mar 18, 1974Jan 20, 1976Laszlo Kalman CsataryIntra-uterine contraceptive device
US3949750 *Oct 7, 1974Apr 13, 1976Freeman Jerre MPunctum plug and method for treating keratoconjunctivitis sicca (dry eye) and other ophthalmic aliments using same
US3971367 *Jun 4, 1975Jul 27, 1976Alza CorporationIntrauterine device having means for changing from uterine-retentive shape to nonuterine-retentive shape
US4326510 *Nov 20, 1979Apr 27, 1982World Health OrganizationBarrier contraceptive torus
US8282612 *Mar 6, 2009Oct 9, 2012Denise H. MillerMethods and devices for intrauterine absorption
Classifications
U.S. Classification128/839, 128/833, 424/432
International ClassificationA61F6/00, A61K9/00, A61F6/14
Cooperative ClassificationA61F6/14, A61K9/0039
European ClassificationA61K9/00M8D, A61F6/14