Method of drug delivery and coated oral dosage forms for use in the method

A coating for a drug wherein said coating is formed from seaweed and/or kelp, the seaweed and/or kelp being of a type which is impervious to gastric acidity but denaturable by alkali found in the intestines. Suitably, the coating comprises a capsule which also incorporates a binder or the coating may comprise barium sulfate or other acid-resistant bulking agents.

FIELD OF THE INVENTION 
THIS INVENTION relates to a method of drug delivery and coated oral dosage 
forms such as capsules for use in the method. 
BACKGROUND OF THE INVENTION 
In order to deliver drugs which may include medicines, vitamins and other 
substances directly to the intestines by oral means, such active 
substances are usually coated with gelatin based materials such as 
capsules or caplets. This is due to the fact that if such substances are 
not coated with a protective coating, such substances would be broken down 
in the highly acidic environment of the stomach. 
Capsules are usually made in rigid or soft form wherein powders or granules 
of a drug or other active ingredient are enclosed in a rigid gelatin shell 
or in soft gelatin shell which soft shell may also contain glycerol as 
well as gelatin to maintain plasticity of the outer shell. Powder 
semi-solids or liquids that do not soften or dissolve the gelatin shell 
can be enclosed. Powder and semi-solids can be encapsulated in a two part 
shell i.e. cap and body whereas liquids may be encapsulated in a capsule 
that is formed, fitted and heat sealed all in one operation using 
especially designed apparatus. 
In addition to inert polymers that control drug diffusion, polymers can be 
designed to dissolve, swell, or degrade in a controlled manner, thereby 
releasing the incorporated drug. It is, however, necessary that the 
polymer be transformed into a water-soluble product that evokes no 
limiting toxic response if the spent product is not to be reclaimed. The 
drug is locked into a polymer matrix (i.e. a drug reservoir) before its 
transformation. The surface area of the polymer-drug mass, the drug 
concentration and solubility characteristics, and the rate of polymer 
transformation affect the rate at which the drug is delivered. The polymer 
structure undergoes a phase change during which it or its by-products are 
removed or eliminated from the body, either during drug release or when 
most of the drug is deployed. 
The polymers investigated for such systems include polyesters, 
polyorthoesters, polyacids, hydrogels, celluloses, polypeptides, 
polyaminotriazoles, and albumin beads. Therapeutic agents investigated for 
delivery from polymeric matrices include narcotic antagonists (naloxone), 
steroids, antimalarials, insulin, enzymes, antibacterials, ophthalmic 
agents, vitamins and anticarcinogens. 
Encapsulation with liposomes promotes the passage of drugs across 
cell-membrane barriers, prolongs plasma lifetime of drugs with short 
biological half-lives, and directs drug disposition. The aqueous 
compartments bounded by bimolecular lipid layers carry the drug-containing 
platform closer to the target site, thus providing higher concentrations 
than the usual systemic therapy. The quantity of the drug or agent 
administered can, therefore, be reduced considerably. 
Active ingredients which are required to be released in different parts of 
the alimentary tract may be coated or packaged in materials which react 
differently with body fluids having varying pH values in different parts 
of the alimentary tract. 
Coatings which resist the action of gastric acids but dissolve under the 
less acidic conditions in the duodenum and intestines are generically 
known as enteric coatings and are applied to capsules as well as tablets. 
Although enteric capsules have been known since the end of the 19th century 
their development has not paralleled that of enteric-coated tablets. This 
has been mainly due to the difficulties in making enteric capsules 
completely resistant to gastric acids. 
Gelatin-based capsules, however, may be made acid resistant by treating 
them with formaldehyde. This process has a disadvantage in that the 
chemical cross linkage changes to the gelatin as a result of the 
formaldehyde treatment can continue during a storage period resulting in 
an undesirable hardening of the capsules. 
Furthermore, trace amounts of formaldehyde in foods and pharmaceuticals 
because of the toxic properties of this substance also raises problems 
with food and drug administration authorities. 
Gelatin capsules may also be coated with a solution of cellacephate, as 
described in U.S. Pat. Nos. 2,491,475 and 2,575,789. Cellacephate is a 
composition consisting of a mixture of gelatin and an alkali metal salt of 
a partial ester of a polycarboxylic acid and a suitable cellulose ether. 
For example, a solution of sodium carbonate in which cellacephate was 
dissolved was mixed with gelatin. Capsules were then made from this 
mixture. U.S. Pat. No. 2,718,667 refers to enteric capsules prepared 
solely from an alkali metal salt of cellacephate. 
Capsules produced by cellacephate/gelatin mixtures however have the 
unfortunate disadvantage of being somewhat unstable on storage because of 
the decomposition of the cellacephate which liberates acetic acid. This 
results in a brittle capsule which is less soluble in the intestines and 
markedly reduces product yield. 
Derivatives of cellulose with enteric properties have also been developed. 
An example of this is U.S. Pat. No. 3,826,666 which refers to a 
preparation of enteric capsules from a mixture of gelatin and the alkali 
metal salt of hypromellose phthalate. This resulted in an effective yield 
of capsules of between 80% and 90%. Further, soft single piece capsules 
with an improved film strength have also been produced by a mixture of 
cellacephate and hypromellose phthalate with gelatin and the addition of 
casein and latex. 
Enteric capsules produced from polymers not based on cellulose have also 
been developed. For example, JP 7310522 refers to a capsule prepared from 
a mixture of gelatin and acrylic copolymers. Commercial gelatin-based 
encapsulation of medicinal substances are disclosed in, for example, 
(i) HUT853800-A, which refers to capsules formed from an emulsion 
containing surfactant, antioxidant and an aqueous solution of alkali metal 
alginate; 
(ii) U.S. Pat. No. 5,362,564, which refers to a seamless capsule containing 
a C.sub.2 -C.sub.6 fatty acid ester of sucrose sandwiched between 
hydrophobic layers and a coating film formed from a ester soluble 
polyhydric alcohol; 
(iii) JO4027352-A, which refers to an enteric soft capsule obtained from 
gelatin, a plasticiser film base and water-soluble polysaccharide 
cross-linked by calcium ions; 
(iv) U.S. Pat. No. 5,204,111, which refers to a capsule containing a 
hydrophobic substance, an isobutylene viscous oil and a polyvalent alcohol 
film coating; 
(v) U.S. Pat. No. 5,330,835, which refers to an alginate capsule formed 
from addition of an alginate solution to a polyvalent metal salt solution; 
and 
(vi) JP59036540-A, which refers to microcapsules formed from gelatin and 
gum arabic, sodium alginate or carrageenan wherein the microcapsules are 
coated with flour, starch, powdered fat, cellulose protein, inorganic 
salt, organic acid salt, amino acid and sugar. 
In all the above mentioned prior art specifications relating to capsules, 
survival of the capsule in the digestive environment of the stomach is 
primarily a function of both the thickness and the resistance to gastric 
acids of the encapsulating material. However, such capsules required the 
employment of complex chemicals such as polymers such as those described 
above and thus the production of such capsules was expensive. Such expense 
was often exacerbated when it was necessary to also employ special 
additives such as agar, glycerine, pectin and various water soluble 
alcohols. 
Other substances which have been used for formation of capsules include 
sucrose, starch, talcum powder, kanzo powder (liquorice powder), rubber, 
grape sugar, crystalline cellulose, lactose titanium dioxide, calcium 
carbonate, ammonium phthalate, cellulose and other associated cellulose 
derivatives, sorbitol, juran gum and polyvinyl alcohol. 
Another major disadvantage of the manufacture of capsules was that such 
manufacture necessitated the use of expensive apparatus especially adapted 
for this purpose. 
Another major disadvantage of the prior art capsules was that the above 
materials had a tendency to break down in the stomach and thus the 
solution of overcoming this problem was to increase the thickness of the 
capsule which, however, could not be universally applied in operation. 
SUMMARY OF THE INVENTION 
It therefore is an object of the present invention to provide a method of 
drug delivery which is effective in use and which may alleviate the 
disadvantages of the prior art. 
The invention therefore, in one aspect, provides a an oral dosage form 
containing a drug for drug delivery incorporating a coating which is 
formed at least partly from seaweed and/or kelp or extracts derived from 
seaweed and/or kelp which is impervious to gastric acidity but denaturable 
by alkali found in the intestines. 
Preferably the seaweed and/or kelp is bound by binder which is also 
impervious to gastric acid(s) but also denaturable by alkali formed in the 
intestines. 
The drug may be dipped in the seaweed and/or kelp or extract derived from 
the seaweed and/or kelp. Preferably the coating may comprise a capsule as 
discussed hereinafter. 
In a preferred form, a sheet is formed at least partly from seaweed and/or 
kelp also using the binder wherein the drug is retained within the capsule 
which is formed by a folding operation wherein adjacent parts of the sheet 
are bonded to each other by the binder. 
The invention also provides a method of manufacture of the capsule which 
includes the steps of (i) placing a drug on the sheet formed from seaweed 
and/or kelp; (ii) folding said sheet to retain said drug within the 
confines of said sheet and (iii) sealing or bonding adjacent parts of said 
sheet with said binder. 
In another arrangement, a capsule may be formed from capsule components 
which incorporate at least some seaweed and/or kelp also incorporating 
said binder wherein each capsule component is formed by extrusion, 
moulding or other suitable process and then each capsule component is 
attached to each other to form a complete shell with the drug retained 
within a hollow interior of the complete shell. 
Suitably a complete shell is formed from two half shell components. Such a 
capsule is suitable for encapsulating drugs in the form of powders or 
semi-solids. 
Alternatively, a capsule may be formed in one operation from seaweed and/or 
kelp at least in part. Liquid drugs, for example, may be encapsulated in 
the capsule that is formed in the single operation. 
Suitably the seaweed or kelp comprises a preparation of seaweed or kelp of 
the genus laminaria known as "konbu" or "kombu" in Japanese or seaweed of 
the variety undaria pinnatifada also known as "wakame" in Japanese. 
However, it will be appreciated that the seaweed sheet may be formed from 
any other variety which may be pressed to form a dry film thickness as 
hereinafter described and which is suitable for this purpose. 
Most preferably the seaweed or kelp is of the shiraita konbu variety, known 
in Japan as "white board kelp". More broadly a family of kelps known as 
macrosystis or sarcophycus may be used which include laminaria. 
Suitably the binder or bonding agent is an alginate of an alkali metal such 
as sodium alginate solution or potassium alginate solution. The alginate 
may have a concentration of between 0.05% and 20% by weight in water. 
However, a preferred concentration is between 0.1% and 3%. 
The alginate binder may operate between temperatures of 1.degree. C. and 
150.degree. C. However the preferred temperature range for its use is 
between 10.degree. C. and 30.degree. C. as this does not result in damage 
to the drug to be encapsulated. Other alginates may be utilised inclusive 
of alginates of Fe, Ag, Sr, Al, Mn, Se, Ca, K or Zn. 
Preferably in the method of the invention the drug is moulded into 
individual pellets which may be of any suitable shape such as cylindrical 
or spherical before being placed on the sheet in one embodiment as 
described which is an especially preferred embodiment. The pellets may 
also be wetted with the binder prior to being placed on the sheet or when 
the pellets are on the sheet. 
The folding of the sheet may be effected by any suitable means such as by a 
manual operation wherein adjacent longitudinal edges of the sheet may be 
folded initially in a transverse or lateral direction and subsequently the 
ends of the folded sheet are further folded to form the capsule. 
Alternatively, one end of the sheet may be wound in a rolling operation by 
suitable apparatus as hereinafter described. 
The seaweed and/or kelp may be initially prepared for encapsulation of the 
drug by a process which may include the steps of: 
(i) application of preservative to the seaweed or kelp which may include 
granular salt in the case of wakame or ash in the case of konbu; 
(ii) washing of the seaweed or kelp to remove the preservative and other 
foreign matter; 
(iii) immersion of the seaweed or kelp in water to allow absorption of 
water or physiological salt solution; 
(iv) removal of the seaweed or kelp from the water and placing of pieces 
thereof on a flat surface; 
(v) covering of the seaweed or kelp with absorbent or blotting material to 
remove excess water in the case of wakame or alternatively with a 
non-blotting material in the case of konbu; and 
(vi) compressing the seaweed or kelp into a flexible film. 
The immersion in water may be for a period to allow absorption of water 
resulting in the seaweed or kelp attaining four or five times its original 
size. The immersion time may be of the order of 5-10 minutes. 
The absorbent material for removal of excess water may be filter paper or 
blotting paper or cloth. 
Compression of the blotted seaweed or kelp is for a suitable period 
resulting in a flexible film of between 0.01 to 0.2 mm uniform thickness. 
More preferably the flexible film is 0.1 mm uniform thickness. The 
compression may be carried out with a board with a weight placed on top or 
other form of commercial fluid actuated pressing apparatus. The 
compression time may be 24 hours in the case of wakame or 20 minutes in 
the case of konbu. 
Alternatively, the seaweed or kelp may be powdered, shredded and/or thinly 
sliced and used with an alginate binder in this form and/or with other 
ingredients such as gelatin, glycerine or other suitable filler and rolled 
prior to being compressed or otherwise processed into a flexible film, 
coating or sheet. 
Alternatively, the seaweed or kelp may be processed into a paste prior to 
being compressed into a flexible film or sheet. The paste is formed by 
reducing the seaweed or kelp to a powder before mixing with sodium 
alginate solution and optionally with water based gelatin solution as a 
filler. The powdered seaweed or kelp is allowed to absorb the solution 
resulting in a paste. 
The sodium alginate solution is most preferably a concentration of 0.2 to 
0.3% in water. The gelatin solution more specifically is of the 
concentration of 50 parts water or 80 parts water to 1 part gelatin 
powder. 
In another variation, the powdered seaweed or kelp may be mixed with the 
sodium alginate and optionally with gelatin filler and allowed to form a 
film on a screen, similar to a silk screen as used for printing, before 
being peeled off and compressed. 
Alternatively small pieces or fine shreds of seaweed or kelp may be bound 
together to form a single flexible sheet by use of the binder. 
Preferably the ash used to dry and preserve the seaweed or kelp is wood 
ash. However, ash from the burning of other suitable materials may be 
used. 
The non-blotting material used to cover the seaweed or kelp may be any 
suitable impervious and non-absorbent sheet material. 
Other variations to the invention include the hand-making of seaweed and/or 
kelp coated capsule by pressing the drug into a sheet of seaweed and/or 
kelp laid over a heavily recessed mould such as a dish, funnel or hole in 
a board. 
The drug, in the form of a powder or paste, is pressed lightly into the 
mould and the neck of the capsule is closed. The neck of the capsule is 
then sealed with sodium alginate solution. 
Preferably an amount of barium sulfate or similar acid resistant 
essentially inert bulking agent that is non-toxic to humans may be added 
to the seaweed or kelp. Preferably 2-50% and more preferably 6-30% of 
bulking agent may be added. The addition of the bulking agent provides 
improved resistance to moisture. The addition of gelatin has a similar 
effect but it is not as satisfactory as barium sulfate. This enables the 
seaweed or kelp preparation to be less affected by humidity. 
According to another aspect of the invention, there is disclosed an 
apparatus for forming a capsule as described above, said apparatus 
comprising: 
(i) a base member having a concave surface; 
(ii) a roller member attached to the base member and capable of 
reciprocatable movement thereto; and 
(iii) a flexible belt rigidly attached to opposed ends of the base member 
in such a manner that the flexible belt is slackly supported on the 
concave surface and interposed between the roller member and the concave 
surface; 
whereby a sheet formed from seaweed and/or kelp which is impervious to 
gastric acidity but denaturable by alkali formed in the intestines is 
initially supported on the flexible belt and subjected to a folding 
operation by movement of the roller member wherein adjacent parts of the 
sheet are bonded to each other by the use of binder applied to the sheet 
to enclose a drug within the sheet. Suitably the roller member is 
cylindrical.

DETAILED DESCRIPTION 
In FIG. 1A is shown a sheet formed from seaweed and/or kelp 1 on which is 
placed drugs 2 for delivery to the intestines. 
In FIG. 1B, binder solution 4 is applied to both ends 5, 6 of the capsule 3 
by means of a brush 7. The ends 5, 6 are then folded over in the direction 
of the arrow 8 resulting in a triangular configuration 8a. The ends 8a are 
then folded over resulting in a capsule 9 as shown in FIG. 1C. 
FIG. 1C shows the capsule 9 in which the ends 10 and 11 have been folded 
over following the application of binder solution. Further binder solution 
is added to the edges 12, 13 and 14 to completely seal the package. 
In FIGS. 2A and 2B, drugs 15 to be encapsulated are placed on sheet 16. 
Binder solution 17 according to the invention is applied along the free 
edges 18 of the wrapping material 16 by means of a brush 19. 
By operation of a lever 20 in the direction 21 the cylindrical roller 22 is 
caused to roll in the direction 23. The lever 20 is pivotally connected to 
operating arms 20a and 20b which are pivotally attached to the base member 
25 and cylindrical roller axle 22a at pivot point 20c and 20d 
respectively. The cylindrical roller axles 22a are located in slotted 
guides 22b (only one side shown for illustrative purposes). There is also 
shown a flexible belt 24 which is attached to base member 25 by fasteners 
28 and in such a manner that it is slackly supported on concave surface 29 
of base member 25. 
In FIG. 2C is shown a cylindrical capsule 26 with crimped ends 27 formed as 
a result of operating the apparatus hereinbefore described and shown by 
FIGS. 2A and 2B. 
Binder solution is applied to the crimped ends 27 to ensure that the 
capsule 26 is completely sealed. 
The term "drug" as used herein includes vitamins, medicines, vaccines, 
proteins, food including health food or any other substance suitable for 
human or animal consumption. The drugs are not limited to solid pills or 
pellets but can extend to oil, wax or jelly-based drugs which are 
suspended, dissolved or otherwise carried in liquids. 
In order to demonstrate the utility of the invention, the following 
experiments were conducted by the applicant in respect of capsules 
constructed in accordance with the invention from konbu or wakame and 
sodium alginate as a binder. 
EXAMPLE 1 
Immersion in fluid 
______________________________________ 
FLUID TESTED RESULT 
______________________________________ 
10-20% Hydrochloric Acid 
No effect 
20% acetic acid No effect 
Plum Vinegar No effect after one week 
Brewing Vinegar No effect after one week 
Artificial Stomach Acid 
No effect after one week 
______________________________________ 
EXAMPLE 2 
Immersion in artificial stomach acid for two hours prior to immersing in 
the following fluids 
______________________________________ 
FLUID TESTED RESULT 
______________________________________ 
Sodium Biocarbonate with pH 8.3 
Peels or breaks open 
within five minutes 
Artificial Intestinal Fluid (pH 7.5) 
Peels or breaks open 
within five minutes 
______________________________________ 
From the results obtained, it is shown that the capsules of the invention 
are impervious to acids inclusive of artificial stomach acids but breaks 
apart in alkali solutions such as artificial intestinal fluid. 
EXAMPLE 3 
In one form of manufacture of capsules in accordance with the invention, 
well dried, salted wakame or other suitable seaweed or kelp is processed 
into a powder of consistency of about 70-120 mesh by high speed grinding, 
blade slicer, ball mill or equivalent. This powder is then rinsed with 
water and adhesive such as sodium alginate (0.3%) is added and optionally 
an additional binder such as gelatin or glycerine is added. The wakame 
powder is then allowed to swell as it absorbs liquid. A layer of the 
thickened or swollen liquid or paste like material is then formed with the 
intention of forming a membrane. In this arrangement, a fine mesh screen 
on a frame (e.g. like a silk screen frame) is obtained, e.g. as used for 
hand crafting paper. This facilitates the production of a flat 
reconstituted seaweed-based membrane or film. 
EXAMPLE 4 
Powdered wakame of 70-120 mesh is obtained as described above in Example 3 
and mixed with sodium alginate solution and further mixed with gelatin, 
glycerine or other binder that provides a suitable surface coating for a 
capsule containing a drug which has already been formed as described 
above. 
EXAMPLE 5 
The powdered wakame of 70-120 mesh prepared as described above in Example 3 
is mixed with sodium alginate and also mixed with conventional raw 
materials used for making capsule shells such as glycerine, gelatin, 
pectins or other binder so as to produce a capsule shell component by a 
conventional process such as by moulding or extrusion. This shell 
component is then be combined with another shell component to provide a 
complete capsule with drug incorporated within the hollow interior of the 
completed shell. Calcium is then added to provide additional opacity if 
required. 
EXAMPLE 6 
A small amount of wakame that has been harvested and cleaned has been 
bagged in a damp state together with granules of salt which acts as a 
preserving agent. The wakame is washed to remove salt and other foreign 
matter and left standing in tepid or room temperature water for 5-10 
minutes (approx.). The wakame absorbs water growing 4-5 times its original 
size. The wakame is removed and excess water drained off and subsequently 
placed within a cotton or nylon cloth and squeezed to obtain the slimy 
liquid extract which exists within. Viscosity between 1500-2000 centipores 
of the liquid extract is optimum. 
6% by weight of barium sulfate is mixed with the extract. In this way, an 
exceedingly acid resistant and to some extent water resistant seaweed 
extract liquid coating material provided. 
EXAMPLE 7 
An extract prepared as described above in Example 6 is mixed with 30% by 
weight barium sulfate. Nine parts of the resulting liquid is then mixed 
with one part of melted gelatin (block or powder form) in a container 
jacketed in hot water. The resultant mix is poured out onto an 
easy-release flat surface such as Teflon PP or PE and dried in a 
refrigerator. The resultant thin sheet is impervious to acid but easily 
broken down by alkalis. This sheet then becomes the raw material for 
making capsules which possess the same excellent acid/alkali performance 
characteristics. 
EXAMPLE 8 
Two standard empty gelatin capsules are taken and 0.8 g of bifidus bacteria 
in powder form is placed in each capsule. One capsule is dipped in the 
liquid extract obtained from the procedure described in Example 6 (i.e. 
without the addition of barium sulfate). The other capsule is dipped in 
the liquid coating material also obtained from the procedure described in 
Example 6 (i.e. with barium sulfate). The two dipped capsules are then 
dried in a refrigerator for 10 hours. The resultant two coated capsules 
are then designated test capsule (1) and test capsule (2). 
For the purpose of a batch test, six test capsules (1) and six test 
capsules (2) were prepared and subjected to the following tests: 
______________________________________ 
Artificial Stomach Acid 
Artificial Intestinal Fluid 
______________________________________ 
Test Capsule (1) 
all 6 unchanged after 1 
all 6 break up in 5 mins 
hour 
Test Capsule (2) 
all 6 unchanged after 2 
all 6 break up in 5 mins 
hrs 
______________________________________ 
EXAMPLE 9 
Three test capsules (1) and three test capsules (2) were prepared as 
described above in Example 7. Each capsule were then placed in the 
following liquids and left for one hour, with regular agitation. Results 
are as shown: 
______________________________________ 
Acid Details Test Capsule (1) 
Test Capsule (2) 
______________________________________ 
10% hydrochloric acid 
not affected 
not affected 
20% acetic acid not affected 
not affected 
Artificial Stomach Fluid pH1.2 
not affected 
not affected 
______________________________________ 
As shown above in regard to test capsules (1) and (2), when these capsules 
are placed in an acid environment, the coating material does not weaken 
but rather becomes stronger. Wakame is used as an ingredient in food is 
popular in Japan and its properties of becoming stronger when served with 
vinegar or other acidic liquids can easily be verified. 
EXAMPLE 10 
Test capsules (1) and (2) when placed in a water environment tend to swell 
or bloat out. Capsules (1) and (2), however, after soaking for one hour in 
an acid environment, if removed and cut open, exhibit a damp and flexible 
outer skin but the condition of the internal material within remains dry 
and unchanged. The condition and strength observed in regard to the outer 
skin suggests that the outer skin can comfortably resist acidity. 
EXAMPLE 11 
A selection of readily available overseas sourced (i.e. non-Japanese 
manufacture) medicines and health foods were obtained which included the 
following: 
(a) elongated but rounded seamless capsules with soft skins which included 
royal jelly and liquid garlic extract); 
(b) soft coatings obtained from tree resin which were used as a coating for 
liquid vitamin E; and 
(c) solid tablets which included bifidus tablets. 
Each health food (a), (b) and (c) were tested in artificial stomach acid of 
pH 1.2. Without exception, all broke down in 20 minutes or less. However, 
when coated with the liquid prepared as described above in Example 6, all 
these health foods survived more than one hour with ease in the same pH 
1.2 environment. During these tests, it was established that ultimate 
survival times varied according to the properties of the surface coating, 
i.e. its absorption properties and the ability of the coating to adhere. 
Improved survival times could be improved by coating a second or even a 
third time. 
EXAMPLE 12 
The addition of barium sulfate also performs the excellent role of allowing 
the progress of coated capsules etc. to be accurately monitored within the 
body by means of x-ray photography. 
In the first clinical trial of this technique, three capsules were loaded 
with powdered bifidus bacteria preparation, coated with the coating 
material prepared as described above in Example 6 and taken orally by a 
healthy patient on an empty stomach. X-ray photos were taken at the 3, 20, 
30 and 60 minute marks, showing the capsules clearly and proving 
conclusively that the coating was working as expected. However, at between 
the 60 and 70 minute mark, each of the tablets passed into the opening of 
the small intestine, beginning to break down almost immediately, 
disappearing fully from the X-ray photos within minutes. 
The performance of the coating of the invention, therefore, is ideal as a 
capsule or coating for oral usage, i.e. the coating survives an hour in 
stomach acid pH 1.2 but breaks down quickly in artificial intestinal fluid 
pH 6.8. To date, no known coating has come close to fulfilling these aims. 
Advantages of the capsules or coatings of the present invention include the 
following: 
(i) the use of seaweed makes a thin but exceedingly strong coating for a 
drug due to the fibrous or cellulosic value of the veins of seaweed leaves 
which are resistant to stomach acids such as dilute HCI but which readily 
breaks down in the alkaline conditions of the intestines. 
(ii) the use of an alginate binder strongly resembles the alginate 
constituents of seaweed and thus the sealant soaks into the fibrous or 
cellulosic structure of the seaweed thereby facilitating strong bonding 
between seaweed pieces or shreds. A possible explanation for this is that 
cation exchange may occur between calcium ions in the seaweed and alkali 
metal ions found in the sealant. 
(iii) the capsules due to their seaweed coating cannot be degraded due to 
excessively high temperatures and are readily transported down the 
intestinal tract and hence are subjected to the same absorption process as 
food particles; 
(iv) the capsules are especially adapted for drugs that are designed to be 
broken down in the small intestine such as: 
(a) bifudus bacteria which are normal flora of the small intestine but 
which reduce in adulthood rendering the small intestine to colitis 
infection; 
(b) vitamins B1, B12, A and C, which require being absorbed through the 
intestines; 
(c) ginseng; 
(d) royal jelly; and 
(e) vitamins and minerals which upon reaching the intestines reduce 
internal discomfort from disorders such as diahorrea and constipation. 
(v) the capsules of the invention are extremely inexpensive to produce 
thereby providing substantive savings on raw material costs when compared 
to the prior art; 
(vi) the capsules are formed from natural products which are part of the 
normal Japanese diet thereby substantially eliminating approval from 
pharmaceutical regulatory authorities such as the FDA; 
(vii) the dosage of the drug which may be encapsulated by the capsules or 
coatings of the invention may be substantially reduced when compared to 
prior art capsules owing to the (a) improved resistance to stomach acids 
and (b) extreme durability in the intestines which properties are unique 
to the present invention; and 
(viii) the capsule technology of the invention will dramatically reduce the 
cost of adminstration of vaccines. The capsules of the invention will 
allow the oral adminstration, in particular, of the synthetic vaccines 
based on peptides. It will therefore eliminate the need for injections and 
nurses and can be reduced to the administration of encapsulated pills 
only.