(cid:38)(cid:68)(cid:83)(cid:86)(cid:88)(cid:74)(cid:72)(cid:79)(cid:3)(cid:40)(cid:91)(cid:75)(cid:76)(cid:69)(cid:76)(cid:87)(cid:3)(cid:20)(cid:19)(cid:20)(cid:19)
`
`Page 1 of 20
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`FOR THE PURPOSES OF INFORMATION ONLY
`
`Codes used to identify States party to the PCI‘ on the front pages of pamphlets publishing international applications under the PCT.
`
`Slovenia
`Slovakia
`Senegal
`Swaziland
`Chad
`Togo
`Tajikistan
`Turkmenistan
`Turkey
`Trinidad and Tobago
`Ukraine
`Uganda
`United States of America
`Uzbekistan
`Viet Nam
`Yugoslavia
`Zimbabwe
`
`
`
`
`
`
`AL
`AM
`AT
`All
`AZ
`BA
`BB
`BE
`BF
`BG
`3.]
`BR
`BY
`CA
`CF
`CG
`CH
`Cl
`CM
`CN
`CU
`CZ
`DR
`DK
`EE
`
`Albania
`Armenia
`Austria
`Australia
`Azerbaijan
`Bosnia and Herzegovina
`Barbados
`Belgium
`Burkina Past)
`Bulgaria
`Benin
`Brazil
`Belarus
`Canada
`Central African Republic
`Congo
`Switzerland
`Cble d'lvoire
`Cameroon
`China
`Cuba
`Czech Republic
`Germany
`Dcnm ark
`Estonia
`
`ES
`Fl
`FR
`GA
`GB
`GE
`GI!
`GN
`GR
`III]
`[E
`1L
`IS
`IT
`JP
`KE
`KG
`KP
`
`KR
`KZ
`LC
`Ll
`LK
`LR
`
`Gabon
`United Kingdom
`Georgia
`Ghana
`Guinea
`Greece
`Hungary
`Ireland
`Israel
`Iceland
`Italy
`Japan
`Kenya
`Kyrgyzstan
`Democratic People's
`Republic of Korea
`Republic of Korea
`Kazakstan
`Saint Lucia
`Liechtenstein
`Sri Lanka
`Liberia
`
`SI
`SK
`SN
`52.
`TD
`TG’
`TJ
`TM
`TR
`TT
`UA
`UG
`US
`UZ
`VN
`YU
`1W
`
`LS
`LT
`LU
`LV
`MC
`MD
`MG
`MK
`
`MI.
`MN
`MR
`MW
`MX
`NE
`NI.
`NO
`NZ
`PL
`PT
`RO
`RU
`SD
`SE
`SG
`
`Lesotho
`Lithuania
`Luxembourg
`Latvia
`Monaco
`Republic of Moldova
`Madagascar
`The former Yugoslav
`Republic of Macedonia
`Mali
`Mongolia
`Mauritania
`Malawi
`Mexico
`Niger
`Nolherlands
`Norway
`New Zealand
`Poland
`Portugal
`Romania
`Russian Federation
`Sudan
`Sweden
`Singapore
`
`Page 2 of 20
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`Page 2 of 20
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`

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`W0 00128976
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`PCTI'U599127093
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`Eield Of The Ingention
`
`The present invention is directed to soft capsules. typically gelatin capsules,
`
`which are used to encapsulate a wide variety of products including pharmaceutical,
`
`nutritional, neutraceutical, cosmetic, cosmeceutical, food, and fertilizer products, and
`
`the like. The capsule contains at least two chambers which are separated from each
`
`other by a substantially impermeable barrier so that different substances may be
`
`encapsulated within the separate Chambers.
`
`c
`
`n
`
`f
`
`elnve 'on
`
`10
`
`15
`
`Protein and protein-like materials, especially gelatin and gelatin derivatives are
`
`used to encapsulate the products produced in several industries. Examples of gelatin
`
`and derivatives thereof and the formation of capsules therefrom are described in
`
`Simpson et at, US. Patent No. 5,074,102 which is incorporated herein by reference.
`
`Such capsules can be used to encapsulate medicinal compounds such as drugs or
`
`vitamins; as a food packaging mechanism for packaging food products such as
`
`powdered instant coffee or spices; in candy manufacturing; in fertilization of plants by
`
`encapsulation of fertilizers, in packing of sensitive seeds in combination with protective
`
`agents and/or fertilizers; and in the packaging of single dyestuffs or mixtures thereof.
`
`More recently such capsules have been used for nutritional, neutraceutical, cosmetic
`
`and cosmetical encapsulated ingredients as well. Such capsules are limited to the
`
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`WO 00128976
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`PCTIUS99I'27093
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`encapsulation of a single substance or compatible substances because the capsule
`
`itself has but a single chamber for storage of the active ingredient.
`
`Some capsules have been designed to provide for multiple dosage units. For
`
`example, Goodheart et al.. US. Patent No. 5,074,426 discloses a capsule which is
`
`divisible into accurate individual dosage units for administering a medicine. The
`
`capsule is easily separated by pulling it into capsule units. The capsule comprises a
`
`first and second capsule unit, each for holding a desired medicinal preparation. The
`
`first and second capsule units are of cylindrical shape and have a longitudinal axis. The
`
`first and second capsule units have first and second ends wherein the first ends are
`
`10
`
`rounded and the second ends are sealed by a closure. The closures of the respective
`
`capsule units abut each other and are detachablv joined to each other.
`
`Another such multiple dosage capsule is disclosed in Makiej, U.S. Patent Nos.
`
`4,793,493 and 4,936,461. These references disclose multiple dose capsules that may
`
`be broken into separately administratable dosages. The hard gelatin capsule
`
`15
`
`comprises a longitudinal tube with a dividing section between respective first and
`
`second ends. The tube has a severable portion relative to first and second walls.
`
`Nugent, US. Patent No. 4,601,896 discloses a pharmaceutical capsule for oral
`
`administration of gastric—sensitive therapeutic agents. The capsule has an outer
`
`housing made from a gastric-fluid impervious composition in which the housing contains
`
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`Page 4 of 20
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`

`

`Wt) 00.928976
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`PCTIU 899197093
`
`a first chamber containing a gastric sensitive therapeutic agent and a second chamber
`
`containing an activator material capable of dissolving the capsule. Prior to taking the
`
`capsule, the patient applies pressure to the capsule to rupture the second chamber
`
`thereby releasing the activator which dissolves the capsule in a predetermined time
`
`thereby releasing the gastric sensitive therapeutic agent in the patient's intestinal tract.
`
`Soft gelatin capsules are a desirable oral dosage form because they are easy
`
`to swallow and are readily digestible. They also provide an adequate encapsulation of
`
`a therapeutically active agent with often prompt release in the gastrointestinal tract.
`
`However, it is often desirable for a patient to receive two or more active agents, which
`
`10
`
`may not be compatible with each other (e.g. may react with each other) in a manner
`
`which irreversibly changes at least one of the active agents.
`
`It would therefore be a significant benefit in the art to provide a soft capsule,
`
`such as a soft gelatin capsule, which enables the administration of two or more
`
`materials (e.g. active agents) at the same time.
`
`15
`
`it would be a further significant benefit in the art to provide a soft capsule which
`
`contains at least two chambers or compartments which are separated by a substantially
`
`non-permeable barrier so that the different materials contained within the separated
`
`compartments cannot adversely affect each other during storage or administration of
`
`the capsule.
`
`Page 5 of 20
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`Page 5 of 20
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`W0 00.328976
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`'PCTI'US99I27093
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`Summary Of The Invention
`
`The present invention is generally directed to a soft capsule typically made out
`
`of gelatin or derivatives thereof having a chamber subdivided into at least two
`
`subchambers. The subchambers are separated from each other by a barrier which is
`
`5
`
`substantially impermeable to the contents of the respective subchambers.
`
`In particular,
`
`the present invention is directed to
`
`a soft capsule for housing at least one agent comprising:
`
`a)
`
`b)
`
`a chamber; and
`
`at least one barrier dividing the chamber into at least two subchambers,
`
`10
`
`said barrier being at least substantially non-permeable to the at least one agent.
`
`In a preferred form of the invention, the barrier comprises a membrane which is
`
`at least substantially non-permeable to the contents of the subchambers.
`
`In another aspect of the present invention, there is provided a method of forming
`
`a soft capsule having a chamber subdivided into at least two subchambers by the
`
`15
`
`barrier as described above.
`
`In a particular aspect of the invention the method
`
`comprises passing at least one ribbon of a material which is at least substantially non-
`
`permeable to said at least one agent between opposed ribbons of a soft capsule-
`
`forming material at a temperature and under pressure sufficient to produce a soft
`
`Page 6 of 20
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`Page 6 of 20
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`W_O 00,-‘28976
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`'PCTIUS991'27093
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`capsule having at least two subchambers separated by a barrier of said substantially
`
`non-permeable material.
`
`Brief Description Of The Drawings
`
`The following drawings in which like reference characters indicate like parts are
`
`5
`
`illustrative of embodiments of the invention and are not intended to limit the invention
`
`as encompassed by the claims forming part of the application.
`
`Figure 1 is schematic view of an apparatus for forming soft capsules having a
`
`chamber subdivided into two subchambers in accordance with the present invention;
`
`Figure 2 is a cross-sectional view of an embodiment of a dual subchamber soft
`
`10
`
`capsule formed by the apparatus shown in Figure 1; and
`
`Figure 3 is a cross-sectional view of another embodiment of a dual chamber soft
`
`capsule formed by the apparatus shown in Figure 1.
`
`Detailed Description Q: The invention
`
`The making of soft capsules especially soft gelatin capsules is well known in the
`
`15
`
`art. Methods for producing soft gelatin capsules are disclosed for example in U.S.
`
`Page 7 of 20
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`Page 7 of 20
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`W9 00:28976
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`PCTI'US99I'27093
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`Patent No. 5,074,102 and references cited therein including US. Patent No. 4,655,027,
`
`US. Patent No. 4,817,367 and US. Patent No.
`
`2.775.267, each of which is
`
`incorporated herein by reference.
`
`The employment of ribbons of soft gelatin material to form a soft gelatin capsule
`
`through the pressure exerted by opposed rotatable dies is well known.
`
`In accordance
`
`with the present invention, at least one additional ribbon of an additional material.
`
`preferably at least a substantially non-permeable material as hereinafter described is
`
`placed between the opposed ribbons of the soft gelatin material. The additional
`
`material is one which is at least preferably substantially non-permeable to the agents
`
`contained within the subchambers. As used herein the term "at least substantially non-
`
`permeable" shall mean a material which does not allow passage of an agent contained
`
`within a subchamber into another subchamber to the extent that the function and/or
`
`structure of the agent is adversely affected. The additional material provides at least
`
`a substantially non-permeable barrier dividing the soft gelatin capsule into at least two
`
`subchambers in which the contents of the respective subchambers do not permeate
`
`into any other subchamber to the detriment of any one of the agents contained with the
`
`subchambers.
`
`10
`
`15
`
`The substantially non-permeable material as defined herein and which is used
`
`to provide a barrier between subchambers will vary depending on the type of agents
`
`20
`
`that are contained within the subchambers. The selection of a suitable substantially
`
`Page 8 of 20
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`Page 8 of 20
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`

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`W0 0008976
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`PCT[US99327093
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`non-permeable material is within the skill of the art. However. a preferred embodiment
`
`of the invention is to employ the same material as used to form the soft capsule since
`
`the soft capsule material is typically selected to be generally at least substantially non-
`
`permeable to the agents contained within the subchambers. Thus, if the capsule is
`
`made of gelatin, the barrier material may be made by gelatin or derivatives thereof. The
`
`barrier material can be made from, in addition to soft gelatin, such materials as cellulose
`
`and derivatives thereof, lipids and derivatives thereof, poiyols and derivatives thereof,
`
`starches and derivatives thereof and the like. The selection of a suitable barrier
`
`material will, of course, depend in part on the agents which are to be contained within
`
`10
`
`the subchambers.
`
`In accordance with the present invention, the barrier material should
`
`be at least substantially non-permeable to the agents if there mixing together would
`
`adversely affect at least one of the agents.
`
`Referring to Figure 1, there is shown a portion of the capsule forming apparatus
`
`employed in the present invention which brings together the respective ribbons of
`
`15
`
`material to form the capsules of the present invention having at least two subchambers.
`
`Other portions of the capsule forming apparatus which are not shown are known and
`
`within the skill of the art.
`
`In particular, the present invention provides for a split wedge comprised of a left
`
`wedge 8 and a right wedge 9. The split wedge is situated above a nip created between
`
`20
`
`a pair of opposed rotatable die rolls, a left die roll 13 and a right die roll 14, which rotate
`
`Page 9 of 20
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`Page 9 of 20
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`W0 0028976
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`PCTI'US99I27093
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`in opposite directions.
`
`In the particular embodiment shown in Figure 1, the left die roll
`
`13 is rotating in a clockwise direction and the right die roll 14 is rotating in a
`
`counterclock direction.
`
`A first or left ribbon 6 of soft material, for example, soft gelatin material is fed
`
`between the left wedge 8 and the left die roll 13. A second ribbon or right ribbon 7 of
`
`soft gelatin material is fed between the right wedge 9 and the right die roll 14.
`
`in accordance with the present invention. a third ribbon or central ribbon 1 of a
`
`barrier material such as a soft gelatin material is fed between the left wedge 8 and the
`
`right wedge 9.
`
`10
`
`Rotation of the respective left and right die rolls 13 and 14 thereby creates the
`
`formation of a multi—chamber soft gelatin capsule 15.
`
`The filling of the left and right subchambers 23a and 23b of the soft gelatin
`
`capsule (see Figures 2 and 3) is accomplished by feeding a first substance “A" through
`
`a right injection lead 4 and simultaneously feeding a second substance "B" through a
`
`15
`
`left injection lead 5 to the nip as the die rolls 13 and 14 rotate and the multi—chamber
`
`capsules 15 are being formed. The gelatin ribbons 1 . 6 and 7 are delivered to the ieft
`
`and right die rolls 13, 14 such that the gelatin ribbons are drawn into the nip from both
`
`sides as the die rolls 13, 14 rotate. Pumps (not shown) control injection leads 4 and 5
`
`Page 10 of 20
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`Page 10 of 20
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`WO 00198976
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`PCTJ'US99I27093
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`via left and right shut-off valves 2 and 3 and will. therefore, operate simultaneously to
`
`achieve the simultaneous filling of subchambers 23a and 23b with an agent such as a
`
`pharmaceutical, vitamin or the like.
`
`Each die roll 13, 14 is formed with a plurality of hemispherical recesses 12
`
`defined at the die roll surface by cutting edges or surfaces 20.
`
`In use. the die rollers 13.
`
`14 rotate in synchrony with each other such that the recesses 12 are in registry at the
`
`nip. and with injection leads 4 and 5. As a result, the fill material is injected between
`
`ribbons 1 and 6 and 1 and 7 when they are reSpectively located over the juxtaposed
`
`recesses 12. The injected fill material forces ribbons 6 and 7 away from central ribbon
`
`10
`
`1 into the respective recess 12 until the capsule is closed by the coming together of the
`
`cutting edges and surfaces 20. Multi-chamber capsules 15 are thus produced
`
`sequentially with a length of laminated gelatin netting 19 therebetween. The cutting
`
`edges and surfaces 20 separate the gelatin netting 19 from the capsules 15 so that the
`
`capsules are produced individually.
`
`15
`
`In rotary die encapsulation machines of the kind illustrated in Figure 1. each die
`
`roll will normally have sufficient axial length to have a substantial number or recesses
`
`raised along its width. As a consequence, whereas the capsules 15 are produced
`
`individually, the laminated ribbon 19 takes the form of a perforated sheet which is drawn
`
`away as waste or recycled.
`
`Page 11 of 20
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`W0 0008976
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`The apparatus of Figure 1 includes left and right wedge heaters 10 and left and
`
`right temperature probes 11 to maintain proper temperature control during capsule
`
`formation and filling.
`
`Once the multi-chamber capsule 15 is formed it is separated from the laminated
`
`gelatin ribbons 19 via a chute assembly 16. The present invention also illustrates left
`
`and right flippers 17 to dislodge capsule material that has not discharged from the die
`
`rolis 13 and 14.
`
`The multi-chamber capsule forming mechanism described above in Figure 1 can
`
`be applied to filled capsules containing, but not limited to. liquids. semi-solids and.
`
`10
`
`powders and particulates with some modification to the mechanism of capsule
`
`formation as discussed in U.S. Patent 5,740,660. incorporated herein by reference.
`
`Embodiments of soft capsules produced in accordance with the present
`
`invention are shown in Figure 2. Referring to Figure 2, a capsule 30 is comprised of an
`
`outer shell 21 formed from the respective ribbons 6 and 7 discussed above in
`
`15
`
`connection with Figure 1. A barrier 22 is formed from the ribbon 1 which is comprised
`
`of a substantially non-permeable material discussed above in connection with Figure
`
`1. The barrier 22 divides the capsule 30 into two subchambers 23a and 23b. Each of
`
`the subchambers 233 and 23b can contain a separate agent even if the active agents
`
`are incompatible with each other since the barrier 22 prevents one agent from
`
`10
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`W0 80128976
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`PCT/US99I27093
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`contacting the other to the extent that neither of the agents are adversely affected with
`
`respect to structure and function.
`
`A further embodiment of a soft capsule is shown in Figure 3. This embodiment
`
`is similar to the embodiment of Figure 2 except that it includes a twist off seal 24. Such
`
`capsules are particularly useful for topical applications and personal care products.
`
`It will be understood that the capsule can contain a plurality of subchambers by
`
`adding additional ribbons of material as discussed above in connection with Figure 1.
`
`Thus, capsules containing three or more subchambers may be constructed within the
`
`spirit and scope of the present invention.
`
`10
`
`15
`
`The capsules of the present invention can be used to house a wide variety of
`
`incompatibie as well as compatible agents including, but not limited to pharmaceutical,
`
`nutritional, nutraceutical, cosmetic and cosmeticeuticai.
`
`The contents of the
`
`subchambers as contemplated in the present invention include, but are not limited to,
`
`active agents such as prescription and non-prescription medications, drugs and the iike,
`
`cosmetics, nutrients, vitamins, neutraceuticals, and the like. The subchambers can also
`
`include one or more non-active agents such as emulsifiers, pH indicators, esterifiers,
`
`surface active agents and the like.
`
`11
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`Page 13 of 20
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`By way of example, a dual subchamber capsule can contain two different active
`
`agents (e.g. an antihistamine and a vitamin complex), the same active agent in different
`
`phases (e.g. a solid phase in one subchamber for slow release and a liquid phase in
`
`another subchamber for rapid release of the active agent), two agents which react
`
`together to form a desired active agent through chemical reaction such as hydrolysis,
`
`oxidation. ester’rfication, salt formation and the like. oil-aqueous phase agents such as
`
`oil soluble vitamins in one subchamber and water-soluble vitamins in another
`
`subchamber. These represent but a few of the possible combinations which may be
`
`employed in capsules prepared in accordance with the present invention.
`
`10
`
`15
`
`The capsules prepared in accordance with the present invention can be used for
`
`internal applications as illustrated above and for external or topical applications. For
`
`example, a capsule can contain a hair relaxing formulation typically including an alkaline
`
`component and a hair treating emulsion formation in another subchamber.
`
`In another
`
`example, a vitamin C emulsion can be used in one subchamber while an alpha—hydroxy
`
`acid formulation having a relatively low pH can be placed in another subchamber.
`
`it will be understood in accordance with the present invention that gelatin and
`
`derivatives thereof are the most common soft capsule forming materials.
`
`It will be
`
`appreciated that other soft capsule forming materials may be employed within the spirit
`
`and scope of the present invention.
`
`12
`
`Page 14 of 20
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`Page 14 of 20
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`

`

`WO 00228976
`
`PCTIUSQ912'TD93
`
`What Is Claimed:
`
`‘l.
`
`a)
`
`b)
`
`A soft capsule for housing at least one agent comprising:
`
`a chamber; and
`
`at least one banter dividing the chamber into at least two subchambers,
`
`said barrier being at least substantially non-permeable to the at least one agent.
`
`2.
`
`The soft capsule of claim 1 wherein the capsule comprises at least one
`
`material selected from the group consisting of gelatin, cellulose, lipids, polyols, starch
`
`and respective derivatives thereof.
`
`3.
`
`The soft capsule of claim 1 comprising more than two subchambers.
`
`4.
`
`The soft capsule of claim 1 wherein the barrier comprises at least one
`
`material selected from the group consisting of gelatin. cellulose, lipids, polyols, starch
`
`and respective derivatives thereof.
`
`5.
`
`The soft capsule of claim 4 wherein the barrier comprises gelatin or a
`
`derivative thereof.
`
`6.
`
`A method of forming a soft capsule for housing at least one agent, said
`
`method comprising passing at least one ribbon of a substantially non-permeable
`
`10
`
`15
`
`13
`
`Page 15 of 20
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`Page 15 of 20
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`

`

`WO 00198976
`
`PCTI'US99I27093
`
`material between opposed ribbons of a soft material to produce a soft capsule having
`
`at least two subchambers separated by a barrier of said substantially non-permeable
`
`material.
`
`7.
`
`The method of claim 6 wherein the opposed ribbons comprise gelatin or
`
`a derivative thereof.
`
`8.
`
`The method of claim 6 comprising passing a plurality of ribbons of a
`
`substantially non-permeable material between said opposed ribbons to produce a soft
`
`capsule having more than two subchambers.
`
`9.
`
`The method of claim 6 wherein the substantially non-permeable material
`
`is selected from the group consisting of gelatin, cellulose, lipids. polyols, starch and
`
`reSpective derivatives thereof.
`
`10.
`
`The method of claim 9 wherein the substantially non-permeable material
`
`is gelatin or derivatives thereof.
`
`11.
`
`Apparatus for the formation of a soft capsule comprising:
`
`a)
`
`first soft material delivery means for delivering a first soft capsule material
`
`between a first wedge and a first roller;
`
`10
`
`15
`
`14
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`Page 16 of 20
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`Page 16 of 20
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`

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`W0 0038976
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`PCTIUS99I'27093
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`b)
`
`second soft material delivery means for delivering a second ribbon of soft
`
`capsule material between a second wedge and a second roller;
`
`0)
`
`at least one barrier material delivering means for delivering a barrier
`
`material between said first and second wedges, said barrier material being substantially
`
`non-permeable to any agent contained within the capsule, said barrier material dividing
`
`the capsule into at least two subchambers; and
`
`d)
`
`active agent delivering means for delivering at least one active agent to
`
`at least one of said subchambers.
`
`12.
`
`The apparatus of claim 11 wherein the first and second soft capsule
`
`10
`
`materials are selected from the gelatin, cellulose, lipids, polyols, starch and derivatives
`
`thereof.
`
`13.
`
`The apparatus of claim 1 1 wherein the barrier material(s) is selected from
`
`the grow consisting of gelatin, cellulose, lipids, polyois, starch and derivatives thereof.
`
`14.
`
`The apparatus of claim 13 wherein the barrier material is gelatin or a
`
`15
`
`derivative thereof.
`
`15.
`
`The apparatus of claim 11 wherein the barrier material is the same
`
`material as at least one of the first and second capsule materials.
`
`15
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`Page 17 of 20
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`PCTIUS99I27093
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`GD
`
`/;
`4/4)
`//
`
`":33.
`
`w
`
`; /
`
`_-— E
`
`iiéfigifi
`4‘ .I-
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`'
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`=
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`t
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`- fiafisafim 6—3f
`1-- 4
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`Page 19 of 20
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`Page 19 of 20
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`

`

`INTERNATIONAL SEARCH REPORT
`
`lateroational application No.
`PCTI'US99f27093
`
`A.
`
`CLASSIFICATION OF SUBJECT MATTER
`
`$61K W48
`lPCU)
`US CL 3124145]. 452, 454. 456
`According to International Patent Classification (IPC) or to both national classification ant. IPC
`B.
`FIELDS SEARCHED
`
`Minimum documentation searched (clarification ayatem followed by classification symbols)
`
`U.S.
`
`:
`
`424M“. 452. 454. 456
`
`Documentation searched other than minimum documentation to the extent that such document: are included in the fields searched
`
`Electronic data base consulted during the international aearch (name of data but: and. where practicable, search tonne used)
`
`WEST search terms: capsule. gelatin. barrier. membrane, ribbon. multidoae. chamber. cellulose, starch. divide. third. compartment.
`aeetion, semipermeable. aeolian
`
`C.
`
`DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Citation of document. with indication. where appropriate. of the relevant passages
`
`Relevant to claim Na.
`
`US 3,732,865 A (HIGUCHI et al) 15 May 1973, see figure 3,
`column 6, lines 25-68, column 7, lines 30-50, column 8, lines 40-
`56, claim 1.
`
`US 4,936,461 A (MAKIEI, Jr.) 26 June 1990, see entire document.
`
`US 5,740,660 A (ROWE) 21 April 1998, see entire document.
`
`Y
`
`Y A
`
`D Further documents are listed in the continuation of Boa C.
`Spa-rial eaIagoi-iea or cited omens:
`document «ran. the [meal atata oa‘ the art which ia llal nominated
`to be all parheular nheaoee
`earlier domment pnhliahad. on or after the international filing date
`duet-neat which may thro- aauhla on priority elaimia} or whiah ia
`cited to eatahliah the publication date or another eltatwn or outer
`apaeial ration tee apaaified)
`document "I'm. to In oral diaoloallfl. uae. aahihition or other
`null“
`
`”unabashed prior to the international filial; data but later than
`the prior-try date :Ia'med
`
`A!
`
`D See patent family annex.
`later doeuetam publialterl alter the mumtioael filing date or priority
`data and not in conflict with the application but and. to meager-ad
`the prizeiple or theory until-lying the luv-um
`doorman: of paelieular I'Ilaaaneo: the claimed invention eanaot be
`Mad novel or mot he eonaiderad to involve an inverting atop
`than Ihe document is taken alone
`
`Want of particular toluenoa: the claimed invention m be
`oonaidarad to involve an attentive mp than tire document
`I:
`eel-hind with one or not. other Iueh Mil-ma. Inch mum“
`beingohviomloapemakifledinunm
`downer“ member of the lane patent family
`
`Date of the actual completion of the international search
`
`23 FEBRUARY 2000
`
`Date of mail? of the international search report
`MAR 2000
`
`
`
`Name and mailing address of the ISNUS
`Cominioner of Fannie and Trademarks
`Box PCT
`Weanington. no. 20231
`(703) 308-1235
`03) 305-3230
`Telephone No.
`Form PCTIISMIO (second aheetXJuly 1992)a
`
`JAMES M. SPEAR
`
`Aull'tol'ized officer
`
`Page 20 of 20
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