EP0228067B1 - Capsules molles sans soudure - Google Patents

Capsules molles sans soudure Download PDF

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Publication number
EP0228067B1
EP0228067B1 EP86117918A EP86117918A EP0228067B1 EP 0228067 B1 EP0228067 B1 EP 0228067B1 EP 86117918 A EP86117918 A EP 86117918A EP 86117918 A EP86117918 A EP 86117918A EP 0228067 B1 EP0228067 B1 EP 0228067B1
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EP
European Patent Office
Prior art keywords
stream
film
forming
composite jet
substance
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP86117918A
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German (de)
English (en)
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EP0228067A2 (fr
EP0228067A3 (en
Inventor
Tadashi Kosaka
Kazuki Omata
Tatsuo Hashimoto
Teruaki Yamazaki
Kazuo Hayashi
Tomiya Hosoi
Kenichi Ikuta
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Taisho Pharmaceutical Co Ltd
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Taisho Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Taisho Pharmaceutical Co Ltd filed Critical Taisho Pharmaceutical Co Ltd
Priority to AT86117918T priority Critical patent/ATE67401T1/de
Publication of EP0228067A2 publication Critical patent/EP0228067A2/fr
Publication of EP0228067A3 publication Critical patent/EP0228067A3/en
Application granted granted Critical
Publication of EP0228067B1 publication Critical patent/EP0228067B1/fr
Expired legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use

Definitions

  • the invention relates to a seamless soft capsule containing encapsulated filling substances, at least one encapsulating wall being formed of a material different from a material forming another encapsulating wall.
  • the invention relates to a method for producing said soft capsule, which comprises:
  • a multicellular soft capsule having its inside partitioned by a film was recently proposed in JP-A-60/109 520 (see PATENT ABSTRACTS OF JAPAN, Vol. 9, No. 254 (308), 1977, October 11, 1985).
  • This document states that the multicellular soft capsule is obtained by partitioning a soft capsule shell composed of an upper film and a lower film into two cells by means of a partitioning film, and filling different drugs into the two cells.
  • two drugs which are not desired to be mixed can be stably included in a single soft capsule.
  • materials having different solubilities and dissolving speeds it is possible to cause one part of a single capsule to be released and absorbed in the stomach and the other part, in the intestines. It is also possible to make one part of the capsule fast-releasing and the other part slow-releasing.
  • the capsule shell Since the proposed multicellular soft capsule is produced by a rotary method or a flat plate method, the capsule shell has seams. Hence, in spite of the aforesaid advantages, it has the defect that the filled drugs leak from the seams, or air comes through the seams to deteriorate the contents oxidatively. Furthermore, by the rotary method or the flat plate method, it is difficult to produce multicellular soft capsules having a small size, and moreover, the cost of production becomes high. Furthermore, since both surfaces of the partitioning film in the aforesaid multicellular soft capsule are formed of the same material, if a drug to be filled in one of the cells reacts with the components of the partitioning film, it cannot be included in such a capsule.
  • EP-A-0 116 311 discloses a multiple soft capsule wherein one or more inner soft capsules are contained together with outer capsule liquor in an outer soft capsule, i.e. the filling of the outer soft capsule consists of the outer capsule liquor and an inner soft capsule "swimming" within said liquor.
  • the inner capsule in turn can have a filling consisting of an inner capsule liquor and a secondary inner capsule "swimming" within said inner capsule liquor, etc.
  • EP-A-0 116 311 proposes a concentric multi-circular soft capsule.
  • a soft capsule of such structure as disclosed in EP-A-0 116 311 has some significant disadvantages.
  • One of these disadvantages is, that the release of a liquor contained in an inner capsule is not independent of the release of the outer capsule liquor. If e.g. two different liquid pharmaceutical substances which must be stored separately within the capsule, are to be released at the same time, this will not be possible.
  • Another disadvantage is, that the selection of wall materials is limited because the wall material of an inner capsule "swimming" in the liquor of the outer capsule has to be stable against both the liquor contained within this inner capsule and the outer capsule liquor.
  • Another object of this invention is to provide a simple and inexpensive method of producing the aforesaid seamless soft capsule, which can easily give capsules of a small size as well.
  • a seamless soft capsule of the type mentioned in the beginning which is characterized in that said soft capsule being composed of a plurality of cells, coalesced to each other, said filling substances being encapsulated in the individual cells, the wall of at least one of said cells being formed of a material different from a material forming the wall of at least one of the other cells.
  • the seamless soft capsule of this invention is produced by a method of the type mentioned in the beginning which is characterized in that
  • the reference numeral l represents a tank holding a film-forming liquid substance A for forming a cell wall; 2, a tank holding a film-forming substance B which is different from the substance A; 3, a tank holding a filling substance C; and 4, a tank holding another filling substance D.
  • the tanks l, 2, 3 and 4 are individually provided with heating means (not shown) for maintaining the substances A, B, C and D at suitable temperatures for maintaining them flowable.
  • the substances A, B, C and D are supplied to the tanks l, 2, 3 and 4 respectively.
  • Metering pumps ll, 2l, 3l and 4l are provided for feeding the substances A, B, C and D of the tanks l, 2, 3 and 4 to a composite nozzle 5.
  • the composite nozzle 5 is a duplex nozzle consisting of outside nozzles 5l and 52 having a semielliptical cross sectional shape resulting from partitioning an elliptical tube by a partitioning wall 50 at its center and inside nozzles 5a and 5b of a smaller diameter disposed nearly centrally in the outside nozzles 5l and 52 respectively.
  • the outside nozzles 5l and 52 communicate with the tanks l and 2, and the inside nozzles 5a and 5b, with the tanks 3 and 4.
  • the composite nozzle 5 faces downwardly along a downwardly flowing stream of a liquid medium e within a capsule-forming tank 6.
  • the specification of the composite nozzle 5 may be freely changed according, for example, to the use of the capsule to be produced.
  • a typical specification is that in Figure 2, the elliptical tube has an outside long diameter d l of 5 to 20 mm and an outside short diameter d s of 3 to l2 mm, and the inside nozzles have an outside diameter of d i of 2 to 9 mm, and the individual tubes have a thickness of 0.l to 2 mm.
  • the liquid medium e formed, for example, of liquid paraffin is sent to a heat exchanger 72 from a recovery hopper 7 concurrently acting as a storage tank by means of a pump 7l.
  • a heat exchanger 72 it is cooled to a moderate temperature of, for example, about 5°C and supplied to the upper portion of the capsule-forming tank 6. It becomes a downwardly flowing stream within the capsule-forming tank 6, and is circulated to the recovery hopper 7 via a capsule recovery tube 6l.
  • a part of the liquid medium e is supplied to a pulse stream-forming device 74 by means of a pump 73 from the hopper 7. It is converted to a regular pulse stream in the pulse stream-forming device 74 and supplied to a pulse stream nozzle 8 provided within the capsule-forming tank 6.
  • the pulse stream nozzle 8 is a circular nozzle provided immediately below, and coaxially with, the composite nozzle 5 and having a slightly larger diameter than the diameter of the elliptical tube of the composite nozzle 5.
  • a pulsating stream of the liquid medium e from the nozzle 8 is extruded toward the center of the nozzle 8 from an annular slit formed within the nozzle 8 in such a manner as to surround a single composite jet stream formed by the composite nozzle 5
  • Film-forming liquid substances A and B for cell wall formation and filling substances C and D to be filled in a capsule are sent under pressure to nozzles 5l, 52, 5a and 5b constituting the composite nozzle 5 by means of the metering pumps ll, 2l, 3l and 4l.
  • nozzles 5l, 52, 5a and 5b constituting the composite nozzle 5 by means of the metering pumps ll, 2l, 3l and 4l.
  • a composite jet stream composed of a stream of the film-forming substance A and a single stream of the filling substance C is extruded into, and along, the downwardly flowing liquid medium flow within the capsule-forming tank 6, and from the nozzle 52, a composite jet stream composed of a stream of the film-forming substance B and a stream of the filling substance D is likewise extruded into, and along, the downwardly flowing liquid medium stream within the capsule-forming tank 6.
  • the two composite jet streams extruded as above, nearly simultaneously with their formation, are coalesced to each other into a single composite jet stream within the downwardly flowing stream of the liquid medium e owing to the surface tensions of the film-forming liquid substances A and B.
  • the speeds of extruding the composite jet streams, and the flow rate of the downwardly flowing stream of the liquid medium e can be varied depending upon, for example, the types of the film-forming liquid substances forming the composite jet streams, the type of the liquid medium e and the size of the composite nozzle, and any skilled person in the art would be able to determine optimum conditions easily by routine experiments. As tentative standards, it is convenient to adjust the extruding speed of each composite jet stream to about 4 to 40 m/min., and the flow rate of the downwardly flowing liquid medium stream to about 5 to 50 m/min.
  • the single composite jet stream so formed undergoes impact of the regular pulse stream of the liquid medium e from the pulse stream nozzle 8, whereby as shown in Figure l, necks or narrowed parts are formed at certain intervals beginning with its leading end.
  • the jet stream is drawn downwardly by the downwardly flowing stream of the liquid medium e , and successively cut off at the neck portions by the downwardly drawing force.
  • Each cut droplet f contains the filling substances C and D encapsulated in the film-forming liquid substances A and B by the surface tension of the substances A and B, and is formed into a seamless capsule, which is roundish as a whole, while moving down through the downwardly flowing stream of the liquid medium e .
  • the capsules formed advance to the hopper 7 via the recovery tube 6l while being cooled and solidified.
  • the capsules are separated from the liquid medium e by a separator 70, supplied to a conveyor 9 provided on one side of the separator 70, and sent to a drying step where they are dried to produce a final product.
  • unitary seamless soft capsules l0 in which a cell a formed of the film-forming substance A and the filling substance C encapsulated in it is coalesced to a cell b formed of the film-forming substance B which is different from the substance A and the filling substance D encapsulated in it, and the cell wall is of a double structure at the coalesced part, as shown in Figure 3.
  • the film-forming substance for cell formation may be any material which can be formed into a thin film from its melt or solution, and after film formation can be solidified by cooling and/or drying.
  • Substances usually employed in forming the shell of a soft capsule may be used in this invention. Examples include film-forming substances composed of gelatin or gelatin derivatives such as succinic gelatin and incorporated therein, plasticizers [such as glycerol, sorbitol, propylene glycol and Carbowax (polyethylene glycol)], essences and flavors (such as peppermint oil, cinnamon oil and strawberry), dyes (such as yellow No. 4, yellow No. 5, red No. l, blue No.
  • opacifying agents such as titanium dioxide and red iron oxide
  • solubility controlling agents such as cellulose acetate phthalate, alkali metal salts of hydroxypropylmethyl cellulose, alkali metal salts of hydroxymethyl cellulose acetate succinate, alkali metal salts of alginic acid, alkali metal salts of polyacrylic acid, methyl cellulose, carboxymethyl cellulose, casein, collagen, agar powder, polyvinyl alcohol and pectin)), etc. selected as desired. It is generally used as a liquid by dissolving it in water under heat.
  • the filling substance to be encapsulated in each cell of the soft capsule of this invention can be any drug which does not dissolve the cell wall nor react with the components of the cell wall. It is preferably liquid when it is to be filled in the cell in accordance with the method of this invention. Accordingly, when the drug is a solid, it is desirably filled in a flowable state as a solution, emulsion or suspension.
  • At least one of a plurality of cells constituting the resulting soft capsule can have a different dissolving time in the digestive tract from at least one of the other cells (for example, whether fast-releasing or slow-releasing), or at least one cell may have different dissolving characteristic from at least one of the other cells (for example, whether released and adsorbed in the stomach or the intestines).
  • the filling substances to be encapsulated in the cells may be varied from cell to cell.
  • a single capsule may be obtained in which a drug expected to be fast-acting is filled in a fast-dissolving cell and a drug desired to be slow-acting is filled in a slow-dissolving cell.
  • a single capsule cell may be obtained in which a drug expected to develop its effect in the stomach is filled in a cell soluble at the stomach, and another drug expected to develop its effect in the intestines is filled in a cell soluble at the intestines.
  • the shape of the soft capsule l0 can be selected by changing the shape of the end surface of the composite nozzle 5 on the extrusion side. Some modified examples of the composite nozzle 5 will be described below.
  • the composite nozzle 5 shown in Figure 4 is composed of duplex outside nozzles 5l and 52 having a cocoon-shaped cross section and smaller-diameter inside nozzles 5a and 5b disposed coaxially within the outside nozzles 5l and 52 respectively.
  • the capsule l0 obtained by using this composite nozzle 5 has a cocoon-shaped cross-section as shown in Figure 5. It is a seamless soft capsule in which filling substances c and d are independently encapsulated in cells a and b .
  • Figures 6 and 8 show other examples of the composite nozzle 5.
  • These nozzles 5 are each divided into three outside nozzles 5l, 52 and 53 by two or three partitioning walls 50 and smaller-diameter inside nozzles 5a, 5b and 5c are disposed centrally in the outside nozzles 5l, 52 and 53 respectively.
  • Figure l0 shows still another example of the composite nozzle 5 in which a large-diameter tube of an elliptical cross-sectional shape is divided into a large-diameter outside nozzle 5l and a small-diameter outside nozzle 52 by a partitioning wall 50 at a site about l/3 as viewed from one end surface of the tube, inside nozzles 5a and 5b having a smaller diameter are disposed in the large-diameter outside nozzle 5l in spaced-apart relationship, and an inside nozzle 5c having a smaller diameter is disposed centrally in the small-diameter outside nozzle 52.
  • the soft capsule l0 produced in this way is a seamless soft capsule composed of a unitary structure of a cell a and two filling substances c and h independently encapsulated in it and a cell b and one filling substance d encapsulated in it, as shown in Figure ll.
  • the soft capsule l0 shown in Figure ll and the method of production using the composite nozzle shown in Figure l0 give a caspsule in which two filling substances c and h are independently encapsulated in a cell having a cell wall of the same material. Hence, they are beneficial when different drugs which are to be released simultaneously from one cell a but should not be mixed beforehand are used as the filling substances c and h .
  • the single composite jet stream formed along the flow of the liquid medium e may be cut to a predetermined length from its leading end in the flowing direction by intermittently increasing the speed of the downwardly flowing stream of the liquid medium e , and intermittently pulling off the composite jet stream downwardly by the quickened downwardly flowing liquid stream, instead of applying a pulsating flow of the liquid medium e sideways to the composite jet stream in the embodiments described above.
  • the single composite jet stream can be cut successively to a predetermined length.
  • one capsule contains a plurality of cells whose cell walls are made of different materials.
  • the present invention is suitable for filling both a substance to be released and absorbed in the stomach and a substance to be released and absorbed in the intestines, or at least two substances having different dissolving times, in a separated state in a single capsule. Since the soft capsule of the invention is seamless, the filled substances can be retained stably while preventing their deterioration by oxidation or otherwise.
  • capsules of any desired sizes can be produced, and capsules having a smaller size than in the prior art can be easily produced at low cost.
  • a film-forming substance A was filled in tank l, and a film-forming substance B, in tank 2.
  • These film-forming substances A and B were extruded from composite nozzle 5 having a outside long diameter (d l ) of l3 mm, an outside short diameter (d s ) of 9 mm and a thickness of l mm ( Figure 2) by metering pumps ll and 2l.
  • the amount of each of the film-forming substances A and B was 65.7 g/min.
  • a filling substance C was filled in tank 3, and another filling substance D, in tank 4.
  • the filling substances C and D were extruded from nozzles 5a and 5b having an outside diameter (di) of 3 mm, an inside diameter of 2 mm and a thickness of 0.5 mm ( Figure 2) by metering pumps 3l and 4l.
  • the amount of each of the filling substances extruded was 36 g/min.
  • Composite jet streams composed of the film-forming subtances A and B and the filling substances C and D flowed at a rate of l0 meters/min.
  • a paraffin oil as a cooling medium e within vessel 7 and heat-exchanger 72 was maintained at 3°C, and flowed downwardly in capsule-forming tank 6 at a flow rate of l5 m/min.
  • a pulsating flow of the paraffin oil generated from pulse flow generator 74 was extruded at equal time intervals from pulse flow nozzle 8 accurately l5 times per second.
  • capsules were formed at a rate of l5 per second at intervals of about ll mm. After drying, each of the caspsules had a long diameter of 8 mm and a short diameter of 6 mm, and the amount of each of the filling substances was 40 mg per capsule.
  • the film-forming substance A is a solution consisting of 20 parts of gelatin, 5 parts by weight of glycerol, 8 parts by weight of sorbitol and 67 parts by weight of purified water which was maintained at about 60°C.
  • the film-forming substance B was a solution consisting of 18 parts by weight of gelatin, 5 parts by weight of glycerol, 2.5 parts by weight of sodium alginate and 74.5 parts by weight of purified water which was maintained at about 60°C.
  • the filling substances C and D were solutions composed of different drugs which were maintained at about 25°C.
  • the film a dissolved in several minutes to release the core c , whereas the film b did not dissolve for more than 2 hours.
  • both the films a and b dissolved within 2 to 3 minutes.
  • film-forming substances A and B were extruded from a composite nozzle having an outside long diameter (D l ) of 7.5 mm, an outside short diameter (D s ) of 3.5 mm and a thickness of 0.5 mm.
  • the amount of each of the film-forming substances A and B extruded was 2l.9 g/min.
  • filling substances C and D were extruded extruded from nozzles 5a and 5b having an outside diameter (d i ) of l mm and a thickness of 0.l mm.
  • the amount of each of the substances C and D extruded was l8.6 g/min.
  • the speed of the composite jet stream at this time was 6 m/min.
  • a paraffin oil was used as a cooling medium e and caused to flow in capsule-forming tank 6 at a rate of 22.5 m/min.
  • a pulsating flow of the paraffin oil generated from the pulse stream generator 74 was extruded from pulse stream nozzle 8 at equal time intervals accurately 50 times per second.
  • capsule-forming tank 6 fifty capsules were formed per second at intervals of about 7.5 mm. After drying, each of the capsule had a long diameter of 3.5 mm and a short diameter of 2.5 mm. The amount of each of the filling substances C and D was about 6.2 mg.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Rigid Containers With Two Or More Constituent Elements (AREA)
  • Wrappers (AREA)

Claims (9)

  1. Capsule molle sans soudure (10) contenant des substances de remplissage encapsulées (c, d, h), l'une au moins des parois encapsulantes étant formée d'une matière (A, B) différente d'une matière (A, B) formant une autre paroi encapsulante, caractérisée en ce que ladite capsule molle (10) est composée de plusieurs cellules (a, b, g) fusionnées entre elles, lesdites substances de remplissage (c, d, h) étant encapsulées dans les cellules individuelles (a, b, g), la paroi d'au moins l'une desdites cellules (a, b, g) est formée d'une matière (A, B) différente d'une matière (A, B) formant la paroi d'au moins l'une des autres cellules (a, b, g).
  2. Capsule molle (10) selon la revendication 1, caractérisée en ce qu'au moins l'une des cellules (a, b, g) et au moins l'une des autres cellules (a, b, g) sont formées de matières de paroi cellulaire (A, B) ayant des temps de dissolution différents dans le tube digestif ou des caractéristiques de dissolution différentes dans le tube digestif.
  3. Capsule molle (10) selon la revendication 1, caractérisée en ce que les substances de remplissage (C, D) encapsulées dans les diverses cellules (a, b, g) sont différentes entre elles.
  4. Capsule molle (10) selon la revendication 1, caractérisée en ce que ladite capsule (10) est composée de deux (a, b) ou trois (a, b, g) cellules.
  5. Procédé de production de la capsule molle (10) de la revendication 1, qui consiste à :
    (a) préparer un courant de jet composé consistant en un courant d'une substance filmogène liquide (A, B) destinée à former une paroi encapsulante et, à l'intérieur dudit courant de substance filmogène (A, B), un courant unique ou plusieurs courants indépendants d'une substance de remplissage (C, D) capable de s'écouler,
    (b) faire avancer le courant de jet composé dans et à travers un courant d'un milieu liquide (e) sensiblement incapable de dissoudre la substance filmogène liquide (A, B), dans le sens d'écoulement du courant de milieu liquide (e),
    (c) former des capsules molles (10) dans le courant de milieu liquide (e) à partir d'une longueur prédéterminée du courant de jet composé, successivement à partir de son extrémité avant, et
    (d) solidifier les parois des capsules molles (10) résultantes ;

    caractérisé en ce que
    (1) l'étape (a) consiste à préparer plusieurs courants de jet composés consistant chacun en un courant de substance liquide filmogène (A, B) destinée à former une paroi cellulaire et, à l'intérieur dudit courant de substance liquide filmogène (A, B), un courant unique ou plusieurs courants indépendants d'une substance de remplissage (C, D) capable de s'écouler, la substance filmogène liquide (A, B) de l'un au moins des courants de jet composés étant différente de la substance filmogène liquide (A, B) de l'un au moins des autres courants de jet composés,
    (2) l'étape (b) consiste à faire avancer lesdits courants de jet composés, en relation d'étroite proximité, dans et à travers ledit courant de milieu liquide (e) sensiblement incapable de dissoudre la substance filmogène liquide (A, a), dans le sens d'écoulement du courant de milieu liquide (e),
    (3) une étape supplémentaire est prévue entre les étapes (b) et (c), ladite étape supplémentaire consistant à fusionner entre eux les courants de jet composés adjacents pour former un courant de jet composé unique dans le courant de milieu liquide (e),
    (4) l'étape (c) consiste à sectionner à une longueur prédéterminée ledit courant de jet composé unique obtenu par ladite fusion, successivement à partir de son extrémité avant dans le courant de milieu liquide (e), et
    (5) l'étape (d) consiste à solidifier les parois cellulaires de la capsule molle (10) résultante.
  6. Procédé selon la revendication 5, caractérisé en ce que chacun desdits courants de jet composés est formé en utilisant une tuyère composée (5) constituée d'une tuyère extérieure (51, 52, 53) et d'au moins une tuyère intérieure de petit diamètre (5a, 5b, 5c) disposée dans celle-ci et en extrudant simultanément la substance filmogène liquide (A, B) par la tuyère extérieure et la substance de remplissage (C, D) par la tuyère intérieure (5a, 5b, 5c).
  7. Procédé selon la revendication 5, caractérisé en ce que le sectionnement du courant de jet composé unique est effectué en appliquant périodiquement un courant pulsatoire d'un milieu liquide (e) par une tuyère (8) de courant pulsatoire entourant le courant de jet composé unique.
  8. Procédé selon la revendication 5, caractérisé en ce que la substance filmogène liquide (A, B) d'au moins l'un des plusieurs courants de jet composés présente un temps de dissolution différent dans le tube digestif ou une caractéristique de dissolution différente dans le tube digestif de ce que présente la substance filmogène liquide (A, B) d'au moins l'un des autres courants de jet composes.
  9. Procédé selon la revendication 5, caractérisé en ce que les courants de jet composés contiennent des substances de remplissage différentes.
EP86117918A 1985-12-26 1986-12-23 Capsules molles sans soudure Expired EP0228067B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT86117918T ATE67401T1 (de) 1985-12-26 1986-12-23 Weiche nahtlose kapseln.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP297182/85 1985-12-26
JP29718285 1985-12-26

Publications (3)

Publication Number Publication Date
EP0228067A2 EP0228067A2 (fr) 1987-07-08
EP0228067A3 EP0228067A3 (en) 1988-06-01
EP0228067B1 true EP0228067B1 (fr) 1991-09-18

Family

ID=17843233

Family Applications (1)

Application Number Title Priority Date Filing Date
EP86117918A Expired EP0228067B1 (fr) 1985-12-26 1986-12-23 Capsules molles sans soudure

Country Status (6)

Country Link
EP (1) EP0228067B1 (fr)
JP (1) JPH06104193B2 (fr)
AT (1) ATE67401T1 (fr)
DE (1) DE3681572D1 (fr)
ES (1) ES2024418B3 (fr)
GR (1) GR3002754T3 (fr)

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US8147871B2 (en) 2004-03-12 2012-04-03 Capsugel Belgium Bvba Pharmaceutical formulations
US8367101B2 (en) 2001-01-30 2013-02-05 Capsugel Belgium Nv Pharmaceutical formulation
US8440224B2 (en) 1999-07-30 2013-05-14 Capsugel Belgium Nv Multi-component pharmaceutical dosage form
US8673350B2 (en) 2003-07-21 2014-03-18 Capsugel Belgium Nv Pharmaceutical formulations
EP2781156B1 (fr) * 2011-11-16 2017-06-14 Morishita Jintan Co., Ltd. Insectifuge

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US5800829A (en) * 1991-04-25 1998-09-01 Brown University Research Foundation Methods for coextruding immunoisolatory implantable vehicles with a biocompatible jacket and a biocompatible matrix core
WO1992019195A1 (fr) * 1991-04-25 1992-11-12 Brown University Research Foundation Vehicule implantable immuno-isolateur et biocompatible servant a apporter des produits therapeutiques selectionnes
GB2338896B (en) * 1998-07-02 2003-05-21 Reckitt & Colmann Prod Ltd Chewable Capsules
CN1109627C (zh) * 2000-01-26 2003-05-28 依钟康 包装不同物料的软胶囊的制造设备和方法
US7670612B2 (en) 2002-04-10 2010-03-02 Innercap Technologies, Inc. Multi-phase, multi-compartment capsular delivery apparatus and methods for using same
JP5105705B2 (ja) 2002-05-09 2012-12-26 中外製薬株式会社 光安定化軟カプセル剤
JP2004105282A (ja) * 2002-09-13 2004-04-08 Freunt Ind Co Ltd 口腔内即溶シームレスカプセルの製造方法
US7025911B2 (en) 2002-09-13 2006-04-11 Freund Corporation Manufacturing method for oral quick-dissolving seamless capsule
EP1608347B1 (fr) * 2003-03-28 2014-08-13 Sigmoid Pharma Limited Forme posologique solide s'administrant par voie orale qui contient des microcapsules sans soudure
WO2005044174A1 (fr) * 2003-11-07 2005-05-19 Freund Corporation Procede et dispositif de production de capsules sans soudure, et capsule sans soudure
US20070134493A1 (en) * 2005-12-08 2007-06-14 Kanji Meghpara Compositions and capsules with stable hydrophilic layers
JP5183104B2 (ja) * 2006-06-19 2013-04-17 森下仁丹株式会社 口臭除去用多重ソフトカプセル
EP2051776A2 (fr) * 2006-08-09 2009-04-29 Koninklijke Philips Electronics N.V. Dispositif et procédé d'activation d'une substance physiologiquement efficace par des ondes ultrasonores, et capsule
JP2009119148A (ja) * 2007-11-16 2009-06-04 Freunt Ind Co Ltd 多色シームレスカプセルの製造装置及び製造方法
JP6091679B1 (ja) * 2016-03-29 2017-03-08 株式会社松風 液滴生成装置

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* Cited by examiner, † Cited by third party
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JPS59131355A (ja) * 1983-01-17 1984-07-28 森下仁丹株式会社 多重軟カプセルの製法
JPS60109520A (ja) * 1983-11-16 1985-06-15 Fujisawa Pharmaceut Co Ltd 多室軟カプセル剤
JPS61151119A (ja) * 1984-12-24 1986-07-09 Taisho Pharmaceut Co Ltd ソフトカプセル

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8440224B2 (en) 1999-07-30 2013-05-14 Capsugel Belgium Nv Multi-component pharmaceutical dosage form
US7883721B2 (en) 2001-01-30 2011-02-08 Smithkline Beecham Limited Pharmaceutical formulation
US8367101B2 (en) 2001-01-30 2013-02-05 Capsugel Belgium Nv Pharmaceutical formulation
US8673350B2 (en) 2003-07-21 2014-03-18 Capsugel Belgium Nv Pharmaceutical formulations
US8147871B2 (en) 2004-03-12 2012-04-03 Capsugel Belgium Bvba Pharmaceutical formulations
EP2781156B1 (fr) * 2011-11-16 2017-06-14 Morishita Jintan Co., Ltd. Insectifuge

Also Published As

Publication number Publication date
JPH06104193B2 (ja) 1994-12-21
ATE67401T1 (de) 1991-10-15
EP0228067A2 (fr) 1987-07-08
GR3002754T3 (en) 1993-01-25
EP0228067A3 (en) 1988-06-01
DE3681572D1 (de) 1991-10-24
JPS62234542A (ja) 1987-10-14
ES2024418B3 (es) 1992-03-01

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