US 3865108 A
A drug delivery device having a drug containing zone associated with and partially defined by a material which swells on contact with body fluids. When swelling occurs, the pressure on the drug containing zone expels the drug from the device.
Description (OCR text may contain errors)
111111661 @tates Fatent 1 1 [111 gamma Marion 1 Feb. 11, 1975 1 1 EXPANDABLE DRUG DIEUVERY DEVICE 2.6431027 6/1953 2.687.729 8/1965  Inventor: William L. Hartop, Bernardsvtlle, 2959250 H960 NJ. 3,102.540 9/1963 3.202.324 8/1965  Assignee. ggliitgrlllhrjrjnaceutical Corporation, 3'490454 H1970 3.559.646 2/1971  Filed: July 9, 1973 3,760,805 973 3.760.984 9/1973 Theeuwes 128/260 X  Appl. No.: 377,350
Related Application Data Primary Examiner-Richard A. Gaudet  Continuation-impart of Ser. No. 144,174, May 17. Assistant Examiner-J. C. McGowan 1971. flbandoned- Attorney, Agent, or Firm-Benjamin F. Lambert 152] 11.5. C1 128/260, 128/270, 222/95  int. CI A6111 31/00 [57 ABSTRACT  Field of Search 128/260, 127, 130. 268,
128/215, 216, 253, 213, 2 W, 2 R, 1 R, 329, A drug delivery device having a drug containing zone 330, 333, 314, 315, 270, 271, 285; 222/92, associated with and partially defined by a material 95, 206, 103, 105 which swells on contact with body fluids. When swelling occurs, the pressure on the drug containing zone (56] References Cited expels the drug from the device.
UNlTED STATES PATENTS 10 Cl 14 D F 706,778 8/1902 Pond 128/270 rawmg gums PATENIED FEB] 1 I975 SHEET 10F 2 INVENTOR Maw/n4. hM/QTOP BY mm, (1 Mg ATTORNEY I EXPANDABILE DRUG DELIVERY DEVICE This is a continuation-in-part of co-pending application Ser. No. 144,174 filed May 17,-1971, now abandoned.
Current methods of introducing medicaments such as prostaglandins, for example, into the uterine cavity for the purpose of abortion and the like require the use of in-dwelling catheters and the continual attention of medical personnel to deliver the drug by use of a syringe or by hydrostatic pressure from an outside reservoir. The device of this invention obviates the need for an indwelling catheter and, more. importantly, eliminates the need for an operator to monitor the administration of the drug.
The device of this invention comprises a generally cylindrical or prismatic base incorporating a substance which swells upon contact with natural body fluids. The base of the device either defines a hollow core containing a medicament or has disposed in a relatively restrained position around or adjacent its outer surface a medicament containing tube or sheath. In other words, the base at least partially defines a medicament containing zone of restricted dimensions. In either case, the medicament is dispensed into the body cavity due to the pressure generated on the medicament containing zone by virtue of the swelling of the base.
The invention may be better understood by reference to the attached drawings, wherein FIG. 1 is a longitudinal cross-section of a device of this invention;
FIG. 2 is a vertical cross-section of the device of FIG. 1 taken along lines 22;
FIG. 3 is a longitudinal cross-section of the device of FIGS. 1 and 2 after use;
FIG. 4 is a vertical cross-section of the used device of FIG. 3 taken along lines 4--4;
FIG. 5 is a longitudinal cross-section of another de vice of this invention;
FIG. 6 is a vertical cross-section of the device of FIG. 5 taken along lines 6-6;
FIG. 7 is a vertical cross-section of still another device of this invention illustrating the same both before and after exposure;
FIG. 8 also is a vertical cross-section of another device of this invention illustrating the same both before and after exposure;
FIG. 9 is a vertical cross-section of yet another device of this invention illustrating the same both before and after exposure;
FIG. 10 is a view in perspective of still another device of this invention;
FIG. 11 is a cross-section of the device of FIG. 10 taken along lines Ill-I1;
FIG. 12 is a vertical cross-section of another device of this invention;
FIG. 13 is a top view of another device of this invention;
FIG. 14 is a top view of yet another device of this invention.
FIGS. 1 through 11 illustrate embodiments of the invention wherein the base of the device defines a hollow medicament filled core. The device of FIGS. 1 and 2 consists ofa base, 1, formed of a material which will expand multi-directionally upon contact with body fluids, the base defining a hollow core, 2. The hollow core, 2, contains a medicament. 3, which is encased in a col- 2 lapsible tube, 4, having a closed end, 5,,projecting outward from the end, 6, of the base, I. When in use, the end of the collapsible tube is severed and the device inserted into a body cavity such as the cervix. The base, 1, will expand multi-directionally upon contact with body fluid and the resistance to expansion offered by the cervix causes the tube to collapse andthe medicament to be dispensed into the body cavity. The cervical canal is gradually enlarged to accommodate thev increased dimensions. Thus, when used to dispense a medicament for the termination of pregnancy, for example, the dilation of the cervix will facilitate the abortion.
FIGS. 3 and 4 illustrate the device of FIGS. I and 2 after use. In FIGS. 3 and 4, the capillary tube, 4, has been compressed and its contents have been expelled into the uterine cavity.
While the device may be of any shape, it is preferred that it be prismatic or cylindrical for enhancing comfort and facilitating insertion. The device also preferably has a tail, 7, to assist in its removal after use. It may also be advantageous to mold the base of the device with an enlarged end portion, 8, to prevent the device from accidentally being inserted completely into the uterus. It is not practical to give a particular dimension for the device since the size employed will depend upon whether the device is used in the nostrils, vagina, for treating rectal disorders, etc.
The base of the device is made either primarily of a material which will itself expand upon contact with body fluids, or is made of an expandable material having incorporated therein a substance which will expand upon contact with body fluids. By expandable material is meant a material which will swell or expand beyond its original or normal limits. Examples of such expandable materials include brown algae, in particular species of the genus Laminaria; polysaccharides derived from brown and red seaweeds, such as alkali metal and ammonium salts of alginic acids and carrageenan; biosynthetic polysaccharides such as xanthan gum; natural gums, such as guar gum, karaya, tragacanth, psyllium seed, and locust bean; cellulose derivatives such as microcrystallinecellulose; synthetic resins derived from cellulose, such as carboxymethylcellulose, and nonionic cellulose gums such as methylcellulose and hydroxypropyl cellulose; synthetic water-absorbing polymers such as polyvinyl alcohol, polyacrylamide, polyvinylpyrrolidone, and ethylene oxide polymers; and modified starches such as pre-gelatinized corn starch. Preferred among the expandable materials are those derived from brown algae and in particular those derived from species of the genus Laminaria.
In practice, the capillary tube may be constructed of any thin, easily collapsible metal or plastic material such as aluminum or Teflon. The material must have sufficient strength to protect the medicament during storage prior to use, but at the time of use must be eas- -ily severable and collapsible. The collapsible tube, and
the hollow core, preferably have an oval cross-section to facilitate collapse under pressure; however, any convenient shape may be utilized.
In some cases, it may be desirable to encase the base in an outer skin of highly flexible water-permeable material, 9a, such as is illustrated in FIGS. 5 and 6. Such a skin assures that the device will not break apart upon softening and swelling when in contact with body fluids. It may be advantageous to form such a skin ofa material having a high modulus of elasticity so as to exert added pressure on the medicament containing zone as the base attempts to expand.
It is possible to further improve the operation of the device by modifying the collapsible tube to prevent entrapment of the drug-due to irregular collapse of segments of the tube. Irregular collapse can be avoided by molding a longitudinal 'rib, b, inside the tube as shown in FIG. 7. Thus, the rib will allow passage of a medicament on either side of it after the tube has collapsed. This may also be accomplished by disposing ribs, 100, at each side of the tube as shown in FIG. 8. Irregular collapse may also be overcome by providing a tube with a rectangular cross-section of appropriate stiffness so that the short side walls, 11d, tend to resist collapse and thus permit passage of the drug through the spaces adjacent them as illustrated in FIG. 9.
While it was indicated at the outset that the device is preferably cylindrical or prismatic, this does not mean that the base must be formed of only one such solid. As illustrated in FIG. 10, the base may be of any shape as long as it has smooth sides and corners, and defines a hollow core into which the medicament or a capillary containing the medicament may be inserted. The device of FIG. 10 consists of a series of four rods, 101, of a material which swells when in contact with body fluids, arranged in a bundle so as to leave an open core, 102, sufficient to hold a small capillary, 104, containing the active drug, 103. The rods may be kept in their illustrated configuration by an outer water-permeable covering, 109, such as the type previously described. The expansion of the rods will fill the void occupied by the capillary and thus extrude the contents into the body cavity.
A particularly adaptable substance for a device of this design is the stalk of the seaweed of the Laminaria family which, when dried, becomes rigid and bone-like. When exposed to water, the stalk will increase in diameter nearly three-fold and become soft and flexible.
As an example of the device illustrated in FIGS. 10 and ll, and the manner in which it functions, four rods of Laminaria, each about 2V2 inches long and about A; of an inch in diameter are bound firmly together by means of fine copper wire. A catheter having an inside diameter of 0.025 inches and an outside diameter of 0.047 inches is inserted longitudinally through the space between the rods, is filled with a vegetable dye solution and one end is clamped off. When the device is immersed in water, within 12 minutes the dye solution can be observed issuing from the open end of the catheter. The dye continues to be expelled very slowly at what appears to be a uniform rate for a total of one hour and minutes. Calculations indicate that the rate of expulsion of the dye cannot have exceeded 1 X l0 ml. per minute. This rate conforms to the concept of the delivery of very small doses of highly active medicaments in a continuous fashion.
FIGS. 12 through 14 illustrate embodiments of the invention wherein the base of the device has a medicament containing tube or sheath disposed in a relatively restrained position around or adjacent its outer surface. Referring specifically to FIG. 12, the base, 201, of the device illustrated constitutes a solid core surrounded by medicament, 203, encased in a sheath,.209. The sheath is not permeable to fluids but the base absorbs body fluids through its ends thus causing the desired effect.
Referring to FIG. 13, the medicament containing tube, 304, of the device illustrated therein is helically wound around the base, 301, and anchored by passing it through the base at either end, 310. As the base expands, medicament is delivered through one of the ends, 310.
Finally, referring to FIG. 14, the medicament containing tube, 404, of the device illustrated therein is secured adjacent to the surface of the base, 401, by pass ing the same through the base at either end, 410. As the base expands, medicament is delivered through one of the ends, 410.
What is claimed is:
l. A device for the delivery of a medicament to a body cavity comprising a base, said base at least partially defining a medicament containing zone of restricted dimensions, said base being expandable and incorporating a material which expands sufficiently upon contact with body fluids to expand said base, said material being selected from the group consisting of brown algae, polysaccharides derived from brown and red seaweeds, biosynthetic polysaccharides, natural gums, cellulose derivatives, synthetic resins derived from cellulose, polyacrylamide, polyvinylpyrrolidone, ethylene oxide polymers, and modified starches, and said medicament containing zone being disposed in pressure responsive relation to said expandable base such that upon insertion of the device into a body cavity pressure is exerted on the medicament containing zone as a result of resistance to expansion by the base within the body cavity which causes the base to compress the medicament containing zone resulting in the medicament contained therein being dispensed into the body cavity.
2. The device of claim 1 wherein said base is comprised of a polymeric material and defines a hollow core which constitutes said medicament containing zone. I,
3. The device of claim 1 wherein said expandable material is Laminaria.
4. The device of claim 2 wherein said core contains a collapsible capillary tube containing said medicament.
5. The device of claim 4 in which said capillary is of oval cross-section.
6. The device of claim 1 in which a collapsible capillary tube containing said medicament is disposed in fixed position adjacent the surface of said base and the peripheral surface of said tube defining an annular medicament containing zone.
7. The device of claim 4 in which said capillary contains an inner rib along substantially its entire length.
8. The device of claim 4 in which the capillary contains a plurality of inner ribs along substantially its entire length.
9. The device of claim 4 in which the capillary tube is of rectangular cross-section.
10. The device of claim 6 in which said capillary contains an inner rib along substantially its entire length.