Drug units and methods for using same

Medical materials for use in treating maladies in living beings, such as ulcers and other conditions of the digestive tract. In one form, a container is provided for a medication which container also contains an adhesive material which is operatively released from the container or exposed at the surface thereof upon biodegradation or dissolution of a protective coating or wall portion of the container under the effects of fluid in the digestive tract in which the container is exposed, such as by swallowing, to permit such adhesive to temporarily bond and retain the container at a select location in the digestive tract so that it may slowly release its contents thereafter to a select portion of the digestive tract. In another form, a multitude of microcapsules, each containing a small quantity of medication, is mixed with an adhesive material, such as a sucralfate other material which may be swallowed as a tablet or dissolved in a liquid such as water. Such microcapsules are carried with the adhesive material to be bonded temporarily therewith to a select portion of the wall of the digestive tract such that, upon biodegradation or dissolution of the walls of the capsules, the contents thereof may be released over an extended period of time to cooperate with the adhesive material in protecting the lining of the digestive tract from acids secreted by the body, food roughage and the like.

SUMMARY OF THE INVENTION 
This invention relates to improvements in medical materials adapted to be 
ingested by swallowing and to retain their integrity until they reach 
select locations in the digestive tract, such as a location in the small 
intestine or the large intestine where they operate to treat or cure a 
disease or malady, such as an ulcer, fistula or the like or to prevent the 
spread or degrading of same. While in a preferred form of the invention, 
the medical material is employed to coat and protect a select portion of 
the lower intestine from erosive or chemical or biological attach, such as 
effected by sucralfate which temporarily binds to the intestinal wall upon 
its release therein, other forms of the invention are operable to treat 
such intestinal maladies and protect the diseased or wound portions from 
the degenerative effects of body fluids and food. 
In the preferred form of the invention, a quantity of a sucralfate formed 
of particles of a-D-Glucopyranoside, B-D-fructofuranosol-, 
octakis-(hydrogen sulfate), aluminum complex manufactured by Marion 
Laboratories, Inc. of Kansas City, Mo., is pressed into a tablet about one 
to two grams in weight and is coated with a biodegradeable or dissolvable 
coating which retains the integrity of the tablet until it reaches a 
select location of the lower intestine after which the coating degrades or 
dissolves allowing intestinal fluid to penetrate and cause release of the 
contents as a paste-like material which coats the intestine at and below 
the point of release. One or more additional treatment drugs mixed with 
the sucralfate or in microcapsules mixed in the tablet may also be 
provided to treat the wound(s) or diseased section of the intestine or 
cure same while the coating material protects the intestinal wall. 
Accordingly it is a primary object of this invention to provide a new and 
improved method for medically protecting and treating diseases of the 
intestinal tract and drug units for effecting such treatment. 
Another object is to provide a method for treating colitis of the lower 
intestinal tract by means of a protective medical agent which is ingested 
by mouth as a tablet or capsule and which remains intact until it reaches 
or approaches the lower intestine and thereafter releases its contents. 
Another object is to provide a method for treating colitis of the lower 
intestinal tract with a material released from encapsulation in that 
portion of the intestinal tract containing ulcers or inflamation. 
Another object is to provide a method and drug units for treating diseases 
of the lower intestine, which drug units are ingested by mouth and remain 
intact as they travel through the digestive tract, until they reach a 
select portion of the intestine located either just before or at a section 
or sections thereof containing a disease, such as ulcers or colitis 
condition, whereupon they release their medication which coats or 
otherwise treats the disease condition to the exclusion of other portions 
of the digestive tract. 
Another object is to provide drug units and methods for treating diseases, 
deficiencies and injuries to the intestinal tract by the combined action 
of a coating and protecting material, such as a sucralfate and a drug 
operable to heal reduce or eliminate diseased or ulcerated conditions. 
Another object is to provide improved time released drug units or mixtures 
operable to treat stomach and intestinal disease conditions and means for 
delivering same to such organs without affecting the organ or organs 
leading thereto. 
With the above and such other objects in view as may hereinafter more fully 
appear, the invention consists of the novel constructions, combinations 
and arrangements of parts as will be more fully described and illustrated 
in the accompanying drawings, but it is to be understood that changes, 
variations and modifications may be resorted to which fall within the 
scope of the invention as claimed.

In FIG. 1 is shown a first form of the invention in the form of a drug unit 
defining capsule or tablet 10 adapted to be swallowed by a person. The 
core 11 of the drug unit 10 is formed of a compressed amount of sucralfate 
provided as a solid oblong shape 12 having rounded or semispherical end 
portions 13 and 14. The mass of core 11 is formed of compressed particles 
of a normally dry material which easily and rapidly absorbs liquids and 
becomes adhesive, upon subjecting same to liquid material such as water or 
fluid of the digestive tract, to permit such material to temporarily 
adhere to surfaces, such as the lining of the digestive tract. Compressed 
particles of sucralfate may form the mass. Such material is formed of 
alpha-D-Glucopyrano-side, B-D-Fructofuranosyl-, octakis[Hydrogen 
Sulphate], aluminum complex. One such form of such material is 
manufactured as a tablet by Marion Lab. Inc., Kansas City, Mo. 64137 under 
the name of Carafate, the tablets of which weigh about one gram, and is 
utilized to treat ulcers and inflammation of the lower esophagus and 
stomach by coating same after the tablet disintegrates under the effect of 
saliva and stomach fluids or after such tablet is placed in a small 
quantity of water to effect such disintegration, which water and tablet 
mixture is swallowed by a patient. The result is a sucralfatealbumin film 
coated on the esophagus and stomach walls, which inhibit certain gastric 
juice activity and coats ulcers or inflammed areas thereof protecting same 
against mechanical and chemical attrition. 
Surrounding and coating the entire outer surface 12S of core 11 including 
center portion 11C and end portions 13 and 14 thereof, is a thin layer 15 
of a dissolvable material, such as a polymer, which dissolves in water or 
body fluid, the thickness and chemical-physical characteristics of which 
coating are such that it will remain surrounding the core 11 and prevent 
intestinal fluids from passing to the material of the core as the capsule 
travels the digestive tract until it reaches a select portion thereof, 
such as that portion of the large intestine which is ulcerated or inflamed 
with colitis or other condition requiring protection from body fluids 
and/or digested food products passing therethrough. At such select 
digestive tract portion, a portion or portions of the coating is 
completely removed by dissolution, erosion or biodegradation such that 
intestinal fluid passes to and is absorbed by the material of the core 11 
allowing such material to expand, break up and flow with body fluid in a 
manner to pass close to and contact a select portion or portions of the 
intestinal wall and to form a coating which adheres thereto for a period 
of time during which it is temporarily adhered to the the intestinal wall 
and protects same against physical attrition and the effects of intestinal 
fluid and bacteria. 
If layer or coating 15 is of non-uniform thickness, a select thin portion 
thereof may dissolve or degrade before the main portion allowing the 
capsule to remain in tact and continue its travel down the intestine while 
its contents slowly flow therefrom to beneficially affect and coat an 
extending portion of the intestinal wall. 
In FIG. 2 is shown a modified form of capsule 20 having a biodegradeable or 
dissolvable coating or preformed shell 22 formed with a cylindrical or 
oblong center portion 23 and rounded end portions 24, 25 and made of 
biodegradeable material such as a polymer, copolymer, starch or the like 
as described hereafter. Completely filling the shell 22 are loose 
particles 21 of a solid material, such as sulcralfate which may rapidly 
absorb and become mixed with intestinal fluid when all or part of the 
material of the shell dissolves or biodegrades at a select location in the 
upper or lower intestine, as described above. 
In a third form of the invention shown in FIG. 3 a swallowable drug unit 30 
is provided defined by an oblong shell or capsule 32 made of gelatin or 
other suitable solid biodegradeable material, the wall 33 of which is of a 
thickness such that the capsule will dissolve or degrade under the effects 
of digestive tract fluid to a degree such that the contents thereof will 
be released when the drug unit reaches a select portion of the upper or 
lower intestinal tract. Filling the interior of the capsule 32 is a liquid 
31 which may serve to coat and/or treat a disease, such as colitis or 
other malady existing at or near the location of the digestive tract where 
such liquid is released from the capsule. 
The capsule 32 has a side wall 33 with a central portion 34 of 
substantially cylindrical shape and semi-spherically shaped end wall 
portions 35 and 36. The wall 33 may be of constant thickness along the 
side and/or end wall portions or may vary in thickness with one or more 
thinner portions thereof adapted to dissolve or degrade before the entire 
capsule degrades to permit the liquid contents to slowly flow therefrom as 
the capsule travels a distance along the intestine. 
In the embodiments of the invention illustrated in FIGS. 1 to 3, it is 
noted that the active contents of the capsules or tablets may comprise a 
coating material, such as a sulcralfate or other material or in 
combination therewith as a mixture or disposed as one or more subcapsules 
or solid units to be dispensed from the main capsule when it dissolves or 
biodegrades at a select location or locations of the intestine, for the 
purpose of treating and curing or reducing the malady being treated. 
Where a second drug or a number of drugs are disposed in microcapsules 
disposed in the sucralfate materials of FIGS. 1 and 2, they may be 
temporarily adhesively bonded to and be retained against a select portion 
of the intestinal wall while they biodegrade and release their contents to 
treat such portion of the intestine to which they are so bonded. 
In the forms of the invention illustrated in the drawings and described 
above, which utilize an intestinal fluid dissolvable coating or capsule, 
it is noted that the dissolving characteristics thereof and the 
thicknesses of the capsules are such that suitable partial or complete 
dissolution to start and effect release of the contained medication, is a 
function not only of such dissolving characteristics but also of the 
thickness of the coating or capsule. Accordingly, in one form of the 
invention, the coatings or capsule walls may be of constant thickness to 
provide substantially simultaneous release or access of intestinal tract 
fluid to the contents of the drug units. In another form, the thickness of 
the coating or containing capsule may vary along its length such that one 
or more portions thereof may dissolve and initiate the release of contents 
or admission of intestinal tract fluid to the interior of the container or 
drug unit prior to the dissolution and release or admission of other 
portions of the container or coating so as to effect a delay or delays in 
the release of the entire contents to provide such medication for 
treatment purposes over an extended period of time and along an extended 
portion of the digestive tract beyond that portion in which initial 
release is effected. 
A number of groups of polymers may be applied to form the capsules 
described or the coatings on the tablets and may be coated or formed in 
thicknesses such as ro effect release of their contents at a select 
location of the digestive tract upon dissolution or biodegradation. Such 
polymers as hydrogels, polyvinyl pyrolodione, poly(vinyl) alcohol, 
ethylene-vinyl acetate copolymer, copolymer of hydroxyethyl methacrylate, 
etc. as well as certain natural waxes may also be employed for the 
coatings and capsules described in wall thicknesses which will effect 
their degradation or dissolution at the descired location of the upper or 
lower intestine. 
Other forms of the invention are noted as follows: 
1. The described drug unit or units which release their contents after 
being swallowed and allowed to travel down the digestive tract, may 
contain a quantity or quantities of a healing substance, such as the 
healing protein epidermal growth factor (EGF) or other medication useful 
in treating and/or healing disease conditions of the stomach, upper or 
lower intestine where release thereof from encapsulation is effected as 
described herein. Such epidermal growth factor may be provided in dry 
powdered form as the sole contents of the dissolvable or biodegradeable 
capsule or microcapsules therein or a mixture of same with the described 
sucralfate to be released therewith to the intestine. The released mixture 
may serve to coat a select area of the intestinal wall adjacent and below 
the location at which release is effected and to treat one or more wounds, 
fistulas or ulcers therein with the growth factor which may serve one or 
both of two purposes. A first of the functions of the growth factor is to 
effect and accelerate healing of the ulcer(s) or wound(s). A second is to 
effect or accelerate the growth of new tissue at the wound and/or along 
that portion of the intestinal lining where the medication is released 
and/or held against the lining as the medication per se and/or 
microcapsules containing same. 
2. A multitude of body fluid dissolvable microcapsules containing a 
suitable medication, such as epidermal growth factor or other medication 
for treating a condition of the intestinal track or stomach, may be mixed 
with a temporary adhesive material, such as sucralfate which mixture is 
pressed into tablet form and coated with dissolvable material as described 
or made to fill a dissolvable capsule to be released therefrom at a select 
location in the upper or lower intestine for retention and release as 
described, after ingestion by mouth or placement by a tool at a select 
location. Biodegradeable adhesives other than sucralfate such as natural 
or synthetic liquid adhesives, may be mixed with the microcapsules or 
disposed therein for release therefrom at a select location or locations 
of the digestive track as described. 
3. If the drug unit contains a coating material or a medication which is 
not sufficiently adhesive to retain it against that portion of the wall of 
the intestinal track adjacent which it is released from encapsulation, a 
suitable biodegradeable adhesive material may be mixed with same or coated 
on the microcapsules containing same within the main container to serve to 
bond such coating material or microcapsules of drug to the portion of the 
intestinal wall against which it is disposed upon release from the main 
container. In other words, the adhesive may be disposed within the main 
container mixed with the particulate coating material, coating the 
microspheres of medication therein and/or contained within such 
microspheres or microcontainers. 
4. In yet another embodiment, the drug and/or coating material contained 
within the main container may be released therefrom by means other than by 
biodegradation or dissolution of the wall of the container. The main 
container may be operable to pass completely through the intestinal tract 
without degrading and may contain a valve operated by a miniature 
actuator, motor or solenoid to open and release all or part of the drug 
and/or coating contents of the container in response to a short wave 
signal, radiation such as microwave radiation, ultrasonic signal or 
magnetic field applied by suitable instrumentation and generating means 
located exterior of the body such as aligned with that portion of the 
intestinal tract containing the disease or ulcer condition. 
Where employed herein and in the claims, the term "biodegradable" or 
"biodegradation" refers to processes whereby body fluid, such as 
intestinal fluid and fluid of the stomach serves to either degrade by 
biological action and/or dissolve an encapsulating material or coating 
surrounding a drug unit or small quantity of drug. 
5. In yet another form of the invention, the containers of FIGS. 1-3 may 
each contain a small permanent magnet which is operable to hold the 
container at a select location of the intestinal tract under the 
attraction force of another magnet, such as a permanent or electro-magnet 
disposed against a select portion of the skin aligned with the abdominal 
wall adjacent said select portion of intestine. Release of the drug or 
medical coating material contents of the magnetically held container or 
drug unit may be effected thereafter by one or more means, such as 
biodegradation or dissolution of a portion, portions or the entire wall of 
the main container or by the operation of a valve in or aligned with an 
opening or openings in the container wall. Such valve or valves in the 
container may be opened from a closed condition by magnetic force or 
radiation, such as a short wave energy field applied from the exterior of 
the body to suitable receiving and valve actuating means. After the drug 
contents of the container have received body fluid to condition same for 
release or have completely or partly flowed from the container past such 
valve, the container may be released from its magnetically held position 
by removal of the magnetic field from its vicinity, and may travel down 
the intestine to the next location where its contents are required to be 
released in a similar manner or excreted from the intestine thereafter. 6. 
In the treatment of diseases of the lower digestive tract such as 
ulcerated colitis, a substantially greater amount of the drug or drug 
mixture released when the encapsulation means therefor degrades or 
dissolves will contact and coat the wall of the lower intestine if the 
waste or feces in the lower intestine is rendered in a loose or highly 
fluid state. Such condition may be effected during treatment by ingesting 
and swallowing a suitable cathartic prior to injesting the drug unit 
described or including such a cathartic in the drug unit. If the stools 
formed in the lower intestine are kept highly fluid or liquid by ingesting 
one or more doses of a cathartic or laxative, release of the drug contents 
of the drug unit while in and/or just prior to the entry of the drug unit 
into the large intestine will permit the contents thereof to flow to and 
contact a substantially larger portion of the wall of the intestine than 
if the waste matter is solid or less fluid. For certain treatment 
procedures, the taking of a suitable dose of a cathartic by mouth and the 
inclusion of a cathartic with the medication of the drug unit will be 
necessary to effect suitable treatment as described. 
In yet another form of treatment procedure involving drug units as 
described above, several liters of a solution of water and the salts of 
sodium chloride,, sodium bicarbonate and potassium chloride taken by mouth 
over a period of several hours will result in clearing the lower intestine 
of solid matter. If one or more of such drug containing pills or capsules 
are taken during or after the drinking of the latter amount of such a 
solution as defined by the medication NuLYTELY (marketed by Braintree 
Laboratories of Braintree, Mass.) and each drug unit is operable to 
release its contents at a select portion of the large intestine, then a 
maximum amount of the described medication or medications contained 
thereby will contact, coat and react on the tissue of the wall of the 
large or lower intestine as described above. Similarly, if it is required 
to coat and treat an ulcer or ulcers in the wall of the stomach or 
duodenum with an epidermal growth factor as described to aid and 
accelerate healing of the ulcer or ulcers, each drug unit may be taken 
between meals with a liquid such as water to assure its dissolution in the 
stomach or duodenum and its contacting the wound tissue or ulcer with the 
epidermal growth factor with or without the sucralfate or other surface 
coating medical material or bioadhesive. 
Thus it is seen that in additional to the encapsulating coating or 
container, the contents thereof may comprise one or more of the following: 
(a) a surface coating medical material such as a sucralfate (b) an 
epidermal growth factor, such as a quantity of a biologically engineered 
and grown growth factor such as G-CSF, GM-CSF or erythropoietin which 
promote the growth of select digestive tract cells such as the cells of a 
wound or ulcer in the intestine, stomach or duodenum and (c) a laxative or 
cathartic if treatment is to be effected of tissue of the lower or large 
intestine. 
7. To help fight infection and further promote healing of an internal wound 
or ulcer, a quantity of the growth factor M-CSF may also be included in 
the drug unit to stimulate the production of interlukins 1 and 3 and 
macrophages. 
8. If the digestive tract wound is bleeding, such as if the wound is a 
bleeding ulcer, a quantity of the growth factor PDGF which promotes blood 
clotting, may also be included in the drug unit to be released in the 
general area of the wound and to cooperate with the one or more other 
medications described in promoting and effecting healing of such wound or 
wounds. 
9. Two or more growth factors, such as one or more promoting select tissue 
growth (erythropoietin), another such aa G-CSF to promote reproduction of 
granulocytes and macrophages, one or more such as M-CSF to promote the 
growth of interlukins and macrophages or platelet derived growth factor 
(PDGF), may be included in the simgle drug unit capsule or tablet to 
cooperate in treating select wounds or wound tissue of the wall of the 
digestive track when delivered, as described, to s select portion or 
portions of the stomach, duodenum, upper or lower digestive tract.