(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:24)
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`Page 1 of 27
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`Page 1 of 27
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`TITLE MODIFIED
`
`4
`
`.
`
`see front page
`
`S P E C I F I C A T I 0 N
`
`MULTICELLULAR SOFT CAPSULES AND PROCESS
`
`AND APPARATUS FOR PRODUCING SAME
`
`TECHNICAL FIELD
`
`5
`
`The present invention relates to multicellular soft
`
`capsules containing a medicinal, cosmetics or food, and to
`
`a process and an apparatus for producing the same.
`BACKGROUND ART
`
`Soft capsules having, for example, a medicinal
`
`enclosed therein are known which comprise a first shell at one
`
`10
`
`side and a second shdfl.at
`
`the other side and which has only
`
`one space between the smflls for containing the contents.
`
`Such capsules are produced by the planar process which
`
`comprises placing over a lower die a first film for forming
`
`the first shell, pouring a liquid medicinal onto the film,
`
`15
`
`placing over the medicinal a second film for forming the
`
`second shell, placing an upper die over the second film and
`
`applying pressure to the upper die to compress the two films
`
`together except at capsule forming portions thereof so that
`
`the nedicinal is enclosed in a space between the two films
`
`20
`
`at the capsule forming portions. or hp the rotary process
`
`which comprises continuously feeding first and second films
`
`to the space between a pair of die rolls and compressing the
`
`two films together except at capsule forming portions thereof
`
`while placing a medicinal into a space between the two films
`
`Page 2 of 27
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`Page 2 of 27
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`Z
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`
`at the capsule forming portions. However,
`
`the conventional
`
`processes are unable to form more than one containing space
`
`between the first shell and the second shell, so that it is
`
`impossible to stably enclose in a single capsule two or more
`
`5 medications which, for example, are pharmaceutically incom—
`
`patible. Further when there is a need for a drug which is
`
`decomposed
`
`in the stomach and a drug which is not so, it
`
`is necessary to separately administer a capsule made of an
`
`enteric film and another capsule made of an intragastrically
`
`10
`
`soluble film. Also when there is a need for a medicinal with
`
`sustained release action, it is necessary to separately give
`
`a rapid release capsule of rapidly soluble film and a delayed
`
`release capsule of prolonged release or enteric film.
`
`15
`
`An object of the present invention is to provide
`
`a soft capsule of novel structure which, although single,
`
`is
`
`adapted to stably enclose at least two kinds of incompatible
`
`contents and which, although in the form of a single soft
`
`capsule, can be made to have one portion of rapidly soluble
`
`20
`
`or intragastrically soluble properties and the other portion
`
`of prolonged release or enteric properties, or to have one
`
`portion with a rapid release action and the other portion with
`
`a delayed release action.
`
`Another object of the present invention is to
`
`Page 3 of 27
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`Page 3 of 27
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`
`provide a process and an apparatus for producing a soft
`
`capsule of novel structure in which the interior space defined
`
`by a shell is divided into a plurality of compartments by
`
`at least one partition.
`DISCLOSURE OF THE INVENTION
`
`The multicellular soft capsule of the present
`
`invention has a shell defining an interior space which is
`
`divided into a plurality of compartments or cells by at least
`
`one partition.
`
`with the multicellular soft capsule of the present
`
`10
`
`invention, different contents can be enc105ed in the different
`
`cells.
`
`'One portion of the capsule can be made different from
`
`the other portion thereof in properties by suitably selec-
`
`tively determining the properties of the partition and of
`
`the constituent portions of the shell as well as the properties
`
`15
`
`of contents to be contained in the plurality of cells.
`
`Accordingly,
`
`two or more kinds of medicinals which. for
`
`example, are incompatible with each other can be stably
`
`enclosed in a single capsule and can be administered in the
`
`form of only one capsule.
`
`A single sustained release capsule
`
`20
`
`can he obtained by
`
`enclosing a rapid release medicinal and
`
`a prolonged release medicinal separately in the plurality of
`
`cells.
`
`The partition and a shell portion on
`
`one
`
`side
`
`thereof may be made to have prolonged release or enteric
`
`properties. and the other shell portion made rapidly soluble.
`
`25
`
`to render one portion of the capsule slow acting and the
`
`Page 4 of 27
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`Page 4 of 27
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`other portion thereof rapidly acting, whereby a single
`
`sustained release capsule can also be obtained.
`
`Further—
`
`more when the partition and a shell portion on one side thereof
`
`are made enteric with the remaining portion made soluble in
`
`S
`
`the stomach, a medicinal which is decomposed
`
`in the stomach
`
`and another medicinal which is not so can be administered as
`
`enclosed in a single capsule.
`
`The process of the invention produces multicellular
`
`soft capsules comprising a first shell and a second shell
`
`10
`
`defining a space therebetween and at least one partition
`
`provided between the shells and dividing the space into a
`
`plurality of cells,
`
`the process comprising feeding to capsule
`
`forming means a first film for forming the first shell, a
`
`second film for forming the second shell and at least one
`
`15
`
`sheet of third film for forming the partition with the third
`
`film positioned between the first and second films, and
`
`compressing the first, second and third films together
`
`except at capsule forming portions thereof so that contents
`
`are placed into spaces between the films at the capsule
`
`20
`
`forming portions.
`
`The apparatus of the invention produces multicellular
`
`soft capsules comprising a first shell and a second shell
`
`defining a Space therebetween and at least one partition
`
`provided between the shells and dividing the space into a
`
`25
`
`plurality of cells,
`
`the apparatus comprising capsule forming
`
`Page 5 of 27
`
`Page 5 of 27
`
`
`
`(a
`
`2
`
`3;.
`
`'dgiijgioz'si 2“».
`
`means composed of a pair of die rolls, first film feeding
`
`means for continuously feeding between the die rolls a first
`
`film for forming the first shell. second film feeding means
`
`for continuously feeding between the die rolls a second
`
`film for forming the second shell. third film feeding means
`
`for continuously feeding at least one sheet of third film
`
`for forming the partition from between the first film and
`
`the second film to between the die rolls, and a plurality of
`
`contents feeding means for
`
`separately placing contents into
`
`spaces between the films at capsule forming portions thereof.
`
`The process and apparatus of the invention produce
`
`multicellular soft capsules having an interior space which
`
`is defined by a shell and divided into a plurality of cells
`
`by a partition.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`Fig.
`
`l is a view in vertical section showing an
`
`' example of multicellular soft capsule according to the
`
`invention;
`
`Fig.
`
`2 is a fragmentary view in vertical section
`
`showing an apparatus of the invention'for producing multi-
`
`cellular soft capsules:
`
`Fig. 3'is a View in vertical section showing a
`modified example of multicellular soft capsule: and
`
`Fig.
`
`4 is a view in vertical section showing
`
`10
`
`15
`
`20
`
`Page 6 of 27
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`Page 6 of 27
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`
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`0211079
`t
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`another modified example of multicellular soft capsule.
`
`DESCRIPTION OF THE PREFERRED EMBODIMENTS
`
`The present invention will be described below in
`
`greater detail with reference to the accompanying drawings.
`
`5
`
`‘
`Fig.
`1 shows an oval soft capsule 10.
`The capsule
`10 comprises an approximately semispherical first shell 11
`
`at one side, an approximately semispherical second shell 12
`
`at the other side and a partition 13 provided therebetween.
`
`The three members 11, 12, 13 are joined together at their peri—
`
`10
`
`pheries by compression.
`
`The two shells ll, 12 define there-
`
`between a space, which is divided into two cells 14, 15 by the
`partition 13.
`The first cell 14 between the partition 13
`
`and the first shell 11 contains first contents A (e.g.
`
`liquid
`
`medicinal), while the_second cell 15 between the partition
`
`15
`
`l3 and the second shell 12 Contains second contents B (e.g.
`
`liquid medicinal).
`
`Fig.
`
`2 shows an example of apparatus for producing
`
`the soft capsule 10.
`
`The production apparatus comprises a capsule former
`
`20
`
`18 composed of a pair of die rolls 16, 17, a first film feeder
`
`20 for continuously feeding between the die rolls 16, 1? a
`
`first film 19 for forming the first shell 11, a second film
`
`feeder 22 for continuou51y feeding between the die rolls l6,
`
`17 a second film 21 for forming the second shell 12,
`
`a third
`
`Page 7 of 27
`
`Page 7 of 27
`
`
`
`film feeder 24 for continuously feeding.a third film 23 for
`
`forming the partition 13 from between the first film 19 and
`
`the second film 21 to between the die rolls 16. 1?, a first
`
`contents feeder 25 for placing the contents A into a space
`
`between the third film 23 and the first film 19 at capsule
`
`forming portions thereof, and a second contents feeder 26
`
`for placing the contents B
`
`into a space between the third
`
`film 23 and the second film 21 at capsule forming portions
`
`thereof.
`
`10
`
`15
`
`20
`
`25
`
`The die rolls 16,
`
`l? are the same as those used
`
`for the conventional rotary apparatus for producing soft
`
`capsules.
`
`The outer peripheral surface of the first die roll
`
`16 is formed with a multiplicity of generally semispherical
`
`film suction cavities 27 for shaping specified portions of
`
`the first film 19 to the form of the first shell 11 by
`
`vacuum suction.
`
`The cavities 27 are arranged at a predeter—
`
`mined spacing axially of the die roll 16 as well as circum—
`
`ferentially thereof. Although not shown.
`
`these cavities 27
`
`communicate with a vacuum pump via a Channel in the die roll
`
`16.
`
`The outer peripheral surface of the second die roll 17
`
`is also similarly formed with film suction cavities 28
`
`corresponding to the cavities 27.
`The mating die rolls 16, 17
`are arranged side by side horizontally and are rotated in
`
`the directions of arrows shown in Pig.
`
`2 at the same speed
`
`so that the corresponding cavities 2?, 28 are opposed to each
`
`Page 8 of 27
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`Page 8 of 27
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`
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`
`other at the nip of the rolls and move downward at the same
`
`speed.
`
`Although not shown,
`
`the first film feeder 20 is
`
`so adapted that a solution {e.g. gelatin solution} serving
`
`as the material for the first film 19 is supplied from a tank
`
`to a preheated rotating film forming roller to continuously
`
`'form the first film 19 in the form of a strip.
`
`The film is
`
`passed over a plurality of unillustrated rollers,
`
`led to a
`
`guide roller 29 positioned close to the first die roll 16
`
`10
`
`thereabove, and fed to the nip of the die rolls 16, 17
`
`obliquely from thereabove.
`
`The second film feeder 22 also
`
`has the same construction as above;
`
`the second film 21 is
`
`passed over a guide roller 30 close to and above the second
`
`die roll 17 and obliquely fed to the nip of the die rolls
`
`15
`
`16, 1? from thereabove.
`
`The third film feeder 24 also has
`
`the same construction as above.
`
`The third film 23 is passed
`
`over a guide roller 31 disposed above the nip of the die
`
`rolls 16,
`
`l? and fed between the die rolls 16. 17 from
`
`immediately thereabove.
`
`20
`
`25
`
`The first contents feeder 25 comprises a multi-
`
`- plicity of pumps 32 which are arranged immediately above the
`
`nip of the die rolls 16, 17. between the first film 19 and
`
`the third film 23-at the first die roll (16} side. These
`
`pumps 32 are arranged axially of the die roll 16 in corre-
`
`sponding relation to the cavities 27 of the die roll 16.
`
`Page 9 of 27
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`Page 9 of 27
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`
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`
`The casings of these pumps 32 also serve to guide and heat
`
`the films 19, 23.
`
`The second contents feeder 26, which has
`
`the same construction as hove, comprises a multiplicity of
`
`pumps 33 arranged immediately above the nip of the die rolls
`
`16. 17, between the second film 21 and the third film 23 at
`
`the second die roll
`
`(1?) side.
`
`of the three films 19, 21, 23 to be fed to the nip
`
`of the pair of die rolls 15, 17 in the above production
`
`apparatus,
`
`the first and second films 19,'21 are drawn into
`
`10
`
`the cavities 27, 28 and shaped to the form of the first and
`
`second shells ll, 12 by vacuum suction before reaching the
`
`nip of the rolls 16, 1?, whereby spaces are formed to provide
`
`interior cells 14, 15. While passing through the nip of the
`
`die rolls 16, 17,
`
`the three films 19, 21, 23 are compressed
`
`15
`
`together progressively from below upward except at the capsule
`
`forming portions corresponding to the cavities 27, 28. When
`
`the films have been compressed together below and around the
`
`capsule forming portions, specified quantities of contents
`
`A,_B are placed into eachspmm between the third film 23 and
`
`20
`
`the first film 19 now shaped in the form of the first shell
`
`11 and into each meme oetween the third film 23 and the second
`
`film 21 in the form of the second shell 12, respectively by
`
`I
`
`the corresponding pumps 32. 33.
`
`The three films are there-
`
`after compressed together above and around the capsule form—
`
`25
`
`ing portions to completely shape capsules 10. The three
`
`Page 10 of 27
`
`Page 10 of 27
`
`
`
`4°
`
`2
`
`‘:.:I..IE"-o'2'121’o'7i§i."
`
`films 19, 21, 23 delivered downward from the nip of the die
`
`rolls 16,
`
`l? are in the form of a compressed sheet 34
`
`except at the portions of capsules 10. While the sheet
`
`further moves downward,
`
`the soft capsules 10 are blanked out
`
`5
`
`by the same device 35 as heretofore used.
`
`The capsules 10
`
`are cleaned and dried in the same manner as conventionally
`
`practiced, whereby multicellular soft capsules 10 like.the
`
`one shown in Fig.
`
`l are produced.
`
`with the production apparatus described above,
`
`the
`
`10
`
`pumps 32, 33 are used for injecting the contents A, B into
`
`the spaces, so that the encapsulation process involves only
`
`greatly reduced variations in the quantity of injection.
`
`With no contents injected into the compressed portion of the
`
`films 19, 21, 23,
`
`the loss of contents can be minimized to
`
`15
`
`achieve a very high yield. Furthermore, highly viscous
`
`contents can be encapsulated similarly.
`
`However,
`
`the multicellular soft capsule of the
`
`present invention can be prepared also by the conventional
`
`planar process.
`
`In this case, a first film for forming the
`
`20
`
`first shell 11 is placed on a lower die, and a predetermined
`
`amount of first contents A are poured onto the film. Next,
`
`a third film for forming the partition 13 is placed over
`
`the contents, a specified amount of second contents B are
`
`poured onto the third film, and a second film for forming
`
`25
`
`the second shell 12 is placed over the contents B. An upper
`
`-10..
`
`Page 11 of 27
`
`Page 11 of 27
`
`
`
`die is placed over the second film, and pressure is applied
`
`to the die to compress the three films together except at
`
`the capsule forming portions thereof. Finally,
`
`the resulting
`
`capsule 10 is blanked out from the sheet by suitable means,
`
`5
`
`followed by the same treatment as above.
`
`Any of the materials usually used for the shell of
`
`soft capsules is usable for forming the shells and partition
`
`of the multicellular soft capsule of the present invention.
`
`An example of useful material is one consisting chiefly of
`
`10
`
`gelatin and further containing a plasticizer, perfume, pigment,
`
`solubility adjusting agent, etc. added thereto as desired.
`
`The medicinals and like contents to be enclosed in
`
`the multicellular soft capsule of the present invention are
`
`preferably liquid. When a solid is to be enclosed, it is
`
`15
`
`preferably encapsulated in the form of a solution or suspension.
`
`The multicellular soft capsule of the present
`
`invention is not limited to the oval shape described but may
`
`be of any shape, such as oblong form,
`
`round form,
`
`tubular
`
`form as seen in Fig. 3, or in the form of a suppository as
`
`20
`
`shown in Fig. 4. Throughout Figs. 1,
`
`3 and 4,
`
`like parts are
`
`referred to by like numerals.
`
`The multicellular soft capsule of the present
`
`invention is usable not only for medicinals but also for
`
`cosmetics,
`
`food, etc.
`
`For cosmetics,
`
`tubular capsules are
`
`25
`
`especially useful.
`
`«all...
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`Page 12 of 27
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`Page 12 of 27
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`
`
`42
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`'2
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`
`« 202'1107-95- .
`n
`
`‘
`
`One portion of the multicellular soft capsule of
`
`the present
`
`invention can be made different from the other
`
`portion thereof in pr0perties by suitably selectively using
`
`the rapidly soluble film, enteric film, prolonged release
`
`5
`
`film, etc. exemplified below for the shells and partition of
`
`the capsule and by placing suitably selected contents into
`
`the two cells.
`
`In this case,
`
`the soft capsule can be given
`
`a beautiful appearance by making the first shell and the
`
`second shell different in color.
`
`The combination of such
`
`10
`
`colors, when associated with the contents, is useful also
`
`for the quality control of the product to be obtained.
`
`A
`
`rapidly' soluble film is formed in the afore—
`
`mentioned manner, for example,
`
`from a gelatin solution
`
`prepared by heating 400 g of gelatin, 100 g of
`
`15
`
`glycerin and 500 g of distilled water at about 600 C with
`
`stirring.
`
`An enteric film is prepared, for example, by
`
`dissolving 30 g of hydroxypropylmethylcellulose phthalate
`
`in 30 ml of 1N aqueous solution of sodium hydroxide, adding
`
`20
`
`the solution to the mixture of 220 g of gelatin,
`
`50 g
`
`of
`
`glycerin and 270 ml of distilled water, heating
`
`the mixture and treating the resulting gelatin solution in
`
`the same manner as above.
`
`A prolonged release film is prepared, for example,
`
`25
`
`from 250 g of gelatin, 30 g of agar powder,
`
`-12—
`
`Page 13 of 27
`
`Page 13 of 27
`
`
`
`50 g
`
`of
`
`glycerin and 300 ml of distilled water,
`
`by
`
`treating these materials in the same manner as in the case
`
`of the rapidly soluble film.
`
`Specific examples of multicellular soft capsules
`
`5
`
`of the present
`
`invention will be described below.
`
`The
`
`formulations in these examples show the quantities of
`
`compounds to be enclosed in one capsule.
`
`Example 1
`
`A 50 g qnantity of 2—rdtroxymethyl—S—chlorou
`pyridine is dissolved in 250 g of polyethylene glycol 400
`
`10
`
`and 400 g of glycerin to prepare contents A. Separately from
`
`this,12 q of ethylcellulose is dissolsed in 600 g of Miglyol
`
`{registered trademark) 812, and 50 g of 2Hnitroxymethylu
`
`6-chlor0pyridine is added to the solution to prepare
`
`15
`
`contents B.
`
`Using a rapidly soluble film {0.8 mm in thickness]
`
`prepared by the foregoing method as the first, second and
`
`third films 19. 21, 23 and further using the foregoing
`
`production apparatus which is equipped with No.
`
`5 oval dies
`
`20
`
`as the pair of die rolls 16, 1?,
`
`the contents A. B are
`
`uniformly injected into first cells 14 and second cells 15
`
`at the same time,
`
`in an amount of OilZ ml
`
`in each cell, by
`
`the contents feeders 25, 26, respectively.
`
`The die rolls 16,
`
`l? are rotated at a film compres—
`
`25
`
`sion temperature of 40 to 50° C to produce 260 multicellular
`
`-13-
`
`Page 14 of 27
`
`Page 14 of 27
`
`
`
`1w
`
`2
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`-:.-:?".-hté'1_‘1'oi7_;93”.
`
`soft capsules per minute, each capsule weighing 485 mg.
`
`A: Z—Nitroxymethyl—6—chlor0pyridine
`
`Polyethylene glycol 400
`
`Glycerin
`
`B: 2—Nitroxymethyl—6~chloropyridine
`
`Miglyol 812
`
`Ethylcellulose
`
`Example 2
`
`10 mg
`
`50 mg
`
`80 mg
`
`10 mg
`
`120 mg
`
`2.4 mg
`
`Multicellular soft capsules are obtained in the
`
`10
`
`same manner as in Example 1 except that the following contents
`
`A, B are placed into the first and second cells 14. 15,
`
`respectively.
`
`A: Thioctic acid amide
`
`Riboflavin
`
`15
`
`Vegetable oil
`
`B: Thiamine nitrate
`
`Tocopheryl acetate
`
`Vegetable oil
`
`Example 3
`
`5 mg
`
`4 mg
`
`100 mg
`
`10 mg'
`
`50 mg
`
`50 mg
`
`20
`
`25
`
`Multicellular soft capsules are obtained in the
`
`same manner as in Example 1 except that the following contents
`
`A, B are placed into the first and second cells 14, 15,
`
`respectively.
`
`A: Nitroglycerin
`
`Propylene glycol
`
`2.5 mg
`
`100 mg
`
`-14-
`
`Page 15 of 27
`
`Page 15 of 27
`
`
`
`It?
`
`i
`
`B: Nitroglyoerin
`
`-
`
`Sudan Blue
`
`Ethylcellulose
`
`c
`
`-
`
`n.
`
`.q..- :[.oziqogggg
`
`.
`
`2.5 mg
`
`‘0.2 mg
`
`2 mg
`
`Panacet 800
`
`'
`
`'_
`
`100 mg
`
`5
`
`Examgle 4
`
`Sustained release soft capsules are prepared, using
`
`the above—mentiOned rapidly soluble film for the first shell
`
`11 and the aforementioned enteric film for the partition 13
`
`and for the second shell 12 and placing the following same
`
`10
`
`contents into the two cells 14, 15.
`
`A: 6—(3.4—DimethoxyphenylJ—l-ethyl-4-mesitylimino-
`
`3—methyl—3,4-dihydro-2(lHJ‘PYrimidinone
`
`10 mg
`
`Vegetable oil
`
`100 mg
`
`B: 6—[3,4-Dimethoxyphenyl)-1-ethyl-4-meSitylimino-
`
`15
`
`3—methy1-3, 4—ainyaro-2 (11-1 1 -pyrimidinone '
`
`.10 mg
`
`Vegetable oil
`
`I
`
`100 mg
`
`ExamEle 5
`
`Sustained release soft capsules are prepared in
`
`the same manner as in Example 4 with the exception of using
`
`20
`
`the aforementioned prolonged release film for the partition
`
`13 and the second shell 12.
`
`A: nitroglycerin
`
`Vegetable oil
`
`B: Nitroglyoerin
`
`25
`
`Vegetable oil
`
`'
`
`2
`
`3 mg
`
`100 mg
`
`3 mg
`
`100 mg
`
`-15—
`
`Page 16 of 27
`
`Page 16 of 27
`
`
`
`.
`r e.
`'
`
`t
`
`..
`
`l-I'
`(a
`_-_', :::'
`
`49:
`
`' :9'2'1'1022939
`
`Example 6
`
`Sustained release multicellular soft capsules in
`
`suppository type are prepared in the same manner as in
`
`Example 1 except that the following contents'a, B are placed
`
`'5
`
`into the first and second cells 14, 15, respectively.
`
`A: Diclofenac sodium
`
`Miglyol 812
`
`B: Diclofenac sodium
`
`15 mg
`
`150 mg
`
`35 mg
`
`Metolose {registered trademark] BUSH 100
`
`50 mg
`
`10
`
`Carbopol
`
`(registered trademark) 940
`
`10 mg
`
`Miglyol 812
`
`100 mg
`
`Examgle 7
`
`Reinforcement multicellular soft capsules are
`
`prepared in the same manner as in Example 1 except that the '
`
`15 .
`
`following contents A, B are placed into the first and second
`
`cells 14, 15 respectively.
`
`A: Vitamin A oil
`
`100.000 IU
`
`L—ascorbic acid
`
`Pyridoxine phosphate
`
`20
`
`Miglyol 812
`
`-
`
`B: L-lysine hydrochloride
`
`L-valine
`
`L-leucine
`
`-
`
`L-threonine
`
`25
`
`L—tryptophan
`
`-15—
`
`50 mg
`
`10 mg
`
`40 mg
`
`5 mg
`
`5 mg
`
`5 mg
`
`5 mg
`
`5 mg
`
`Page 17 of 27
`
`Page 17 of 27
`
`
`
`L-methionine
`
`L—phenylalanine
`Miglyol 812
`
`ExamEIe 8
`
`.5111" 139‘1‘151'6
`
`319'. .
`
`.
`
`-5 mg
`
`5 mg
`l30 mg
`
`I
`
`S
`
`Cream-containing tubular multicellular soft capsules
`
`are prepared in the same manner as in Example 1 except that
`
`the following contents A, B are placed into the first and
`
`second cells 14, 15, respectively.
`
`10
`
`15
`
`A: Vitamin A oil
`Tocopheryl acetate
`
`'
`
`I
`
`200,000 10
`.10 mg
`
`Monostearic acid glyceride
`
`B: L—ascorbic acid
`
`Polysorbate 80 ’
`
`-
`
`2 mg
`
`10 mg
`
`2 mg
`
`Propylene glycol
`Before use,
`
`'_
`'
`I 150 mg
`the tip of the capsnle is out off,
`
`and the contents A, B are mixed together on the palm and
`
`then applied to the skin.
`
`-17-
`
`Page 18 of 27
`
`Page 18 of 27
`
`
`
`CLAIMS
`
`1. A multicellular soft capsule having an interior
`
`space defined by a shell and divided into a plurality of
`
`cells by at least one partition.
`
`2. A multicellular soft capsule as defined in claim
`
`1 wherein the shell comprises a first shell portion at one
`
`side and a second shell portion at the other side. and said
`
`at least one partition is provided between
`
`the
`
`shell
`
`portions.
`
`3. A multicellular soft capsule as defined in claim
`
`1 wherein the cells are two in number.
`
`4. A multicellular soft capsule as defined in claim
`
`3 wherein the shell comprises a first shell portion at one
`
`side and a second shell portion at the other side. and
`
`one partition is provided between the shell portions.
`
`5. A multicellular soft capsule as defined in claim
`
`4 wherein the first shell portion,
`
`the second shell portion
`
`and the partition are each a rapidly or intragastrically
`
`soluble film or a prolonged release or enteric film.
`
`6. A multicellular soft capsule as defined in claim
`
`4 wherein the first shell portion is a rapidly or intragastri-
`
`cally soluble film, and the second shell portion and the
`
`partition are a prolonged release or enteric film.
`
`7. A multicellular soft capsule as defined in claim
`
`3 or 4 wherein a rapidly soluble medicinal is enclosed in one
`
`Page 19 of 27
`
`Page 19 of 27
`
`
`
`J,
`
`.
`
`‘
`
`- n
`:
`I
`
`nun-A..—
`
`19.
`
`r.
`
`a
`
`IIJI
`
`'-". 6211073
`IllilllI
`at
`
`of the cells, and a prolonged release medicinal is enclosed
`
`in the other cell.
`
`8. A process for producing_multicellular soft
`
`capsules which comprise a first_she11 and a second shell
`
`defining a space_therebetween and at least_one partition
`
`provided between the shells and dividing the space into a
`
`5
`
`.plurality of cellst the process comprising_feeding to capsule
`
`forming means a first film for forming the first shell. 3
`
`second film for forming the second shell.and at least one
`
`sheet of third film for forming the partition with the third
`
`film positioned between the first and second-films, and
`
`10
`
`compressing the first, second and third films together
`
`except at capsule forming portions thereof so that contents
`
`are placed into spaces between the films at the capsule
`
`forming portions.
`
`9. A process for producing multicellular soft
`capsules which comprise a first shell and a second shell
`defining a space therebetween_and one partition provided
`between the shells and dividing the space into too cells,
`the process comprising feeding to capsule forming means a
`
`first film for forming the first shell. a second film for
`
`forming the second shell and one sheet of third film for
`forming one partition with t he third film peeitioned between
`the first and second Ifilms, and compressing the three films
`together except at capsule forming portions thereof so that
`
`5
`
`10
`
`Page 20 of 27
`
`Page 20 of 27
`
`
`
`20
`
`;.a0 9;.-
`
`contents are placed into a space between the third film and
`
`the first film and into a space between the third film and
`
`the second film at the capsule forming portions.
`
`10. A process for producing multicellular soft
`
`capsules as defined in claim 9 wherein the capsule forming
`
`means is a pair of die rolls, and the three films are
`
`continuously fed between the die rolls,
`
`the three films being
`
`5
`
`compressed together except at the papsule forming portions
`
`thereof while placing the contents into the space between
`
`the third film and the first film and into the space betWeen
`
`the third film and the second film at the capsule forming
`
`portions.
`
`11. An apparatus for producing multicellular soft
`
`capsules which comprise a first shell and a second shell
`
`defining a space therebetween and at least one partition
`provided between the shells and dividing the space into a
`
`S
`
`plurality of cells,
`
`the appmmtus comprising capsule forming
`
`means composed of a pair of die rolls, first film feeding
`
`means for continuously feeding between the die rolls a first
`
`film for forming the first shell. second film feeding means
`
`for continuously feeding between the die rolls a second
`
`_lO
`
`film for forming the second shell, third film feeding means
`
`for continuously feeding at least one sheet of third film
`
`for forming the partition from between the first film and
`
`the second film to between the die rolls, and a plurality of
`
`Page 21 of 27
`
`Page 21 of 27
`
`
`
`-.-;»
`
`21
`
`0211079
`
`contents feeding means for separately placing centents into_;
`spaces between the films at capsule forming portions thereof1
`I
`12. An apparatus for pfoducing multicellular soft-
`capsules which comprise a first shell and a second shell
`defining a space therebetween and_one partition provided
`between the shells and dividing the space into two cells.
`apparatus comprising capsule forming means composed of al
`
`the
`
`15
`
`5
`
`pair of die rolls. first film feeding means for continuously
`
`feeding between the die rolls a first film for forming the
`
`first shellr second film feeding means for continuously feed—
`
`ing between the die rolls a second film for forming the second
`
`10
`
`shell, third film feeding means for continuously feeding one
`
`sheet of third film for forming one partition from between
`
`the first film and the second film to between the die rolls,
`
`first contents feeding means for placing contents into a
`
`Space between the third film and the first film at capsule
`
`15
`
`forming portions thereof, and second contents feeding means
`
`for placing contents into a space between the third film and
`
`the second film at capsule forming portions thereof.
`
`13. An apparatus for producing multicellular soft
`
`capsules as defined in claim 12 wherein the pair of die rolls
`
`are arranged side by side horizontally, and the third film
`
`feeding means feeds its film to between the die rolls from
`
`5
`
`immediately thereabove,
`
`the first and second film feeding
`
`means being adapted to feed their films to between the die
`
`Page 22 of 27
`
`Page 22 of 27
`
`
`
`22
`
`l'
`
`1 2g,«¢g1ggaot-s:z
`
`l "
`
`o
`
`rolls_obliquely from thereabove.
`
`the contents feeding means
`
`being adapted to place the contents into the spaces between
`
`the films from thereabove at the capsule forming portions.
`
`14. An apparatus for producing multicellular soft
`
`capsules as defined in claim 13 wherein each of the contents
`
`feeding means comprises pumps arranged between the films
`
`concerned immediately above the die roll.
`
`Page 23 of 27
`
`Page 23 of 27
`
`
`
`0211079
`
`
`
`Page 24 of 27
`
`Page 24 of 27
`
`
`
`Q'oz119?9;
`
`
`
`
`
`Page 25 of 27
`
`Page 25 of 27
`
`
`
`INTERNATIONAL SEARCH REPORT
`unnnumuuumnunun. PCT/J985/0004L--
`
`O 2 1 1 0 7 9
`
`may Inlnlcrnlhonll Patent Cllulficwm «monommcuummmulc '
`1mm" A61K 7/00, A61K 9/48, am 3/07. 123? 1/04
`
`A61K 7/00, A61K 9/48, A61J 3/07,
`A611 1/00, A61K 9/00, 3653 9/04
`
`Jitsuyo Shinan Koho
`Kokai Jitsuyo Shinan Koho
`III; DOCUMENT: CONSIDERED TO I! RELEVAN? "
`cutsonovoocumem "minoocanon. vim-Wan «mum-Mum"
`
`1926 - 1985
`1971 - 1985
`
`macaw-Nun
`
`Apr1l 22,1985 (22. 04- 85)
`
`_
`DE, A, 2317140 (Walla AG) 17 October 1974
`(17. 10. 74) Column 9,
`lines 2 to 10 (Family nashi)
`
`DE, A, 2052668 (Gillette Co.) 6 May 1971
`(06.05. 71) Column 11, lines 2 to 26 5
`SE, B, 355492 & CA, A1, 942673 6
`AT, B, 316757
`
`JP, A; 55-122710 (Kyoto Ceramic Kabushiki Knisha)
`20 September 1980 (20. 09. 80) Column 4, line 12 to
`column 5, line 9 5 DE, A1, 3005350 6
`GB, BZ, 2043444 & US, A, 4293540
`
`JP, Bl, 45-359 (Jacob A. Glassman)
`8 January 1970 (08. 01. 70) Column 4, lines 32 to 40,
`(Family nashi)
`
`JP, Y1, 16--1127 (Takeuchi Kintaro) 1 February 1941-
`(01. 02. 41) Column 1
`(Family nashi)
`
`JP, Y1, 16- 11981 (Takeuchi Kintaro) 16 August 1941
`(16 08. 41) Column 1
`(Family nashi)
`
`'W angering a! dud documents: “
`mmmdmmM‘b-m -
`. 1- .MM «mung
`W In be a! pamcular Monaco
`
`“1" WMMWIWWMGWNWI‘ .
`:f mail.
`1." down-m Much my mm 00001: on M emu) or
`whicnlocmdnuuummo kahuna-mum
`Mummlruaon moan-d)
`‘0' dawn-M "1011111qu on! Guam. uu swim or
`'- Clam
`"P mmwwsmdwmmmmommamm
`mmmmmnmm
`
`‘T‘ but mum MWWMWM
`_muumnmmmmmw
`NMUWWNW
`.T mmummmmmWw
`Wine,
`'7' «mamuummmmfim
`NWbMMmmm-nnnmm
`h mwmwm m mm. Inch
`mmmuo-mmnhm
`
`- “I‘M‘md'h-MAMM -
`
`.
`
`.-
`
`mnemuwdmwmm'
`
`.
`
`qqgg1nnAuuuComanamaatnomunummus.u0n-
`April 6,19854
`(06. 04. 85)
`‘WSourchingAmhomy'
`:‘ggpanesg Patent 0ff1Cg.
`Fm PUMA/210 (mood amen (Detour 1981)
`
`"
`
`Page 26 of 27
`
`Page 26 of 27
`
`
`
`I
`
`I Mural ruronumou corr'nuuso mm: 11-13 sacoun sneer
`
`Inltmltlonlunullnllonflo. PCTIJPSSIDOOGI
`
`O 2 1 1 O 7 9
`
`JP, A, 59-22552 (Fuji Capsule Kabushiki Kaisha)
`4 February 1984 (04. 02. Bé) Column 5, Fig. 1
`(Family nashi)
`
`1?, A, 57-86351 (Tokai Capsule Kabushiki Kaisha)
`29 May 1982 (29. 05. 82) Column 3, Fig. 1
`(Family nashi)
`
`-
`
`10-14
`
`10-14
`
`
`
`
`
`
`
`
`
`
`V. D OBSERVATIONS “HERE CERTAIN CLAIMS WERE FOUND UHSEAHCI'IAILE"
`
`This mismamnai search room In: he! been ambushed In manual of mm claim um Huck 1H2) In} In! the {allowing rum:
`
`LE Clam nummra.......... _ because may rum to subnct manor u no! mulmd ta In nurcmd by lhia Authority. namely:
`
`1U Churn numbers.......... -. Manna may relm In part: all ma inurnttlonll lnnilcltlofl that no rum comnrywitn 1h- [gr-scrim mun.
`merlta no such an extent an: no meanmgful inlcrnauarul search can be can-50d out '3. ”mule-fur:
`
`VLD OBSEIWAT‘IBNS WHERE UNITY OF INVENTION IS UCKING “
`
`Yflis Inlemltional Snitching AutI'IorIly found Munich inuntionl In his imamnmnll apdrcalbon u Ioiim:
`
`
`
`
`
`AI III mum nudiilomi March in» arm flrnaIy paid by tho manual. tI‘III INIITIIHMII search upon cm III ull'chl DH claim. 01' I11!
`mum-l mmlunon.
`
`
`
`3D As any m or m. mum ldfllhonli much fans won um paid by the apmlcant. mi: mum-ml uuca rum cow-r; onry than
`
`churned 1h- :niernltronll applicauon for which I." were paid. $.21!me calm:
`
`No mun-Id 16¢“me search I." mrl umly paid by Ira Imliclnl. GMuarlw. fill-i Intimaflonal "mm mm I: minded to lilo
`mum lira mmbonad :n In. churns: it I ounrod by claim I'Iul'anI'I:
`
`
`
`
`
`
`
`
`
`
`4 D M an ulrchlma clllml mum In ”ITEM will-Ion! effort iuflll'yina I.l'| Idclflonul In. In. Intnmtlonal Sunshine Authofll'y dld not inn!-
`umm 0! my naamaml In.
`“9m on PM"!
`D
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