EP0531257A1 - Méthode et dispositif pour contenir et administrer une dispersion contenant des peptides - Google Patents

Méthode et dispositif pour contenir et administrer une dispersion contenant des peptides Download PDF

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Publication number
EP0531257A1
EP0531257A1 EP92810655A EP92810655A EP0531257A1 EP 0531257 A1 EP0531257 A1 EP 0531257A1 EP 92810655 A EP92810655 A EP 92810655A EP 92810655 A EP92810655 A EP 92810655A EP 0531257 A1 EP0531257 A1 EP 0531257A1
Authority
EP
European Patent Office
Prior art keywords
vessel
peptide
containing dispersion
gas
volume
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.)
Withdrawn
Application number
EP92810655A
Other languages
German (de)
English (en)
Inventor
Bruno Dr. Galli
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Ciba Geigy AG
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.)
Filing date
Publication date
Application filed by Ciba Geigy AG filed Critical Ciba Geigy AG
Publication of EP0531257A1 publication Critical patent/EP0531257A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D83/00—Containers or packages with special means for dispensing contents
    • B65D83/0005—Containers or packages provided with a piston or with a movable bottom or partition having approximately the same section as the container
    • B65D83/0033—Containers or packages provided with a piston or with a movable bottom or partition having approximately the same section as the container the piston being a follower-piston and the dispensing means comprising a hand-operated pressure-device at the opposite part of the container
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/02—Membranes or pistons acting on the contents inside the container, e.g. follower pistons
    • B05B11/028—Pistons separating the content remaining in the container from the atmospheric air to compensate underpressure inside the container
    • B05B11/029—Pistons separating the content remaining in the container from the atmospheric air to compensate underpressure inside the container located on top of the remaining content
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/1001—Piston pumps
    • B05B11/1023—Piston pumps having an outlet valve opened by deformation or displacement of the piston relative to its actuating stem
    • B05B11/1026—Piston pumps having an outlet valve opened by deformation or displacement of the piston relative to its actuating stem the piston being deformable and its deformation allowing opening of the outlet

Definitions

  • the invention relates to a method for the stable storage of peptide-containing dispersions according to the preamble of patent claim 1. Furthermore, the invention also relates to a device suitable for the stable storage of peptide-containing dispersions according to the preamble of patent claim 11.
  • Dispersions containing peptides have a wide range of uses in many diseases of the human body.
  • the peptides often correspond to human or animal hormones.
  • Insulin, glucagon and calcitonin are particularly important peptides.
  • Calcitonin is mainly used for the treatment of Paget's disease, especially cases of severe hypercalcaemia, for cancerous bone diseases and especially for the treatment of postmenopausal osteoporosis.
  • the widely used animal calcitonins for example eel calcitonin, porcine calcitonin and in particular salmon calcitonin, show good effectiveness, but have the disadvantage that they are identified by the body as foreign substances and corresponding neutralizing antibodies can be formed.
  • these animal calcitonins in particular Salm calcitonin (eg Grauer et al. 1990, J. Bone Min. Res. 5, 387-391 or Levy et al. 1988, J. Clin. Endocrinal. Metab. 67, 541-545 and further literature cited therein) with time its effectiveness, it gets used to and can even lead to the formation of antibodies and induced counter-reactions.
  • Human calcitonin which corresponds to the human hormone, the so-called human calcitonin.
  • Human calcitonin is considered to be less effective than animal calcitonins and therefore administered in higher concentrations, but has the great advantage that the body regards it as the body's own substance and therefore does not form any neutralizing antibodies against human calcitonin.
  • dispersions containing calcitonin or aqueous solutions show physical instabilities due to aggregation phenomena. In particular, they tend to form fibrils and can thus increase and even gel the viscosity of the dispersion, in particular of the aqueous solution.
  • the human calcitonin is usually in a storage-stable lyophilized form in its own container and is dissolved in the desired dispersant.
  • a significant simplification of the provision of this desired dispersion or solution is that the lyophilisate and the solvent are stored in separate chambers in a double-chamber syringe and are only combined immediately before the injection. Since the injection as a method of administration is perceived as unpleasant by many patients, methods of administration via the mucous membranes, in particular the nasal mucous membranes, are often used. However, the use of nasal applicators is in turn restricted by the problem that dispersions containing peptides, in particular those containing higher concentrations of human calcitonin, have a very limited shelf life.
  • a two-chamber solution, as with the two-chamber syringe does not appear to be expedient either, since the lyophilized human calcitonin is not immediately and completely soluble in the solvent in the event of a spray.
  • peptide-containing, in particular human calcitonin-containing, dispersions in particular aqueous solutions
  • the process for the stable storage of the peptide-containing dispersion should also not require any additional effort with regard to special storage conditions.
  • the device used for stable storage should be simple and inexpensive to manufacture.
  • the device should also be usable for the application of the peptide-containing dispersion.
  • the device according to the invention can be used particularly well for nasal application of peptide-containing dispersions, in particular for the application of human calcitonin.
  • the device according to the invention is designated as a whole by 1 in FIGS. 1 and 2.
  • the same components and elements of the device are provided with the same reference numerals in FIGS. 1 and 2.
  • the two illustrated exemplary embodiments are, in particular, so-called nasal applicators.
  • the nasal applicator 1 has an approximately cylindrical vessel 2 with an inner wall 21 of the vessel. the vessel is closed on one side with a metering and application device 3.
  • the dosing and application device 3 is, for example, screwed onto one end of the vessel 2 or welded on by friction and closes this one end of the vessel 2 in a gas-tight, in particular air-tight manner.
  • a useful volume 10 is provided in the interior of the vessel, which is designed to hold a peptide-containing dispersion C and can be changed with the aid of a gas-tight, in particular air-tight, displacement device 9.
  • the peptide-containing dispersion C is preferably a peptide-containing aqueous solution which is contained in the useful volume with the exclusion of air. It is preferably an aqueous solution of a calcitonin, in particular human calcitonin, in a concentration of up to 100 mg / ml, preferably of up to 5 mg / ml.
  • the metering and application device 3 comprises a pressure-operated disposable metering valve 4.
  • the valve 4 is of conventional design, so that the same can be described in more detail is waived.
  • an approximately conical nasal adapter 5 is plugged onto the dosing and application device 3 and has a central passage 6.
  • the metering valve 4, which is designed for the passage of the peptide-containing dispersion C, is connected on the output side to the passage channel 6 and thus represents a connection between the useful volume 10 in the interior of the vessel and the passage channel 6 in the nasal adapter.
  • the nasal adapter 5 can, as in FIG 1, can also be covered with an attachable closure cap 7. At the end of the nasal adapter 5 opposite the outlet opening of the passage 6, the latter has a flange-like widening 8, which serves as a contact surface for the fingers when the metering valve is actuated.
  • the gas-tight displacement device 9, which limits the usable volume 10 on one side, is preferably designed as a drag piston which is arranged inside the vessel 2 and can be displaced along the vessel wall 21 without tilting and thus changes the available usable volume 10.
  • the drag piston has circumferential sealing lips which slide along the inner wall of the vessel and thus seal the usable volume 10 in a gas and liquid-tight manner.
  • the useful volume 10 for the peptide-containing dispersion C is limited by the metering and application device 3, the inner wall 21 of the vessel and the drag piston 9.
  • the end of the cylindrical vessel 2 opposite the metering and application device 3 is open. As shown, it can be closed by a base 14, which may be removable. This has the advantage that this increases the stability of the device. However, the base 14 has at least one air inlet opening 15 in order to ensure the function of the device 1.
  • the exemplary embodiment of the device 1 according to the invention shown in FIG. 2 has a slightly modified structure.
  • the vessel 2 has a vessel bottom 22.
  • the usable volume 10 is limited by the trailing piston 9, the inner wall 21 of the vessel and the bottom 22 of the vessel.
  • the metering and application device 3, in particular the metering valve 4, is provided with a riser 11 which passes through the trailing piston 9 approximately in the middle and extends to the bottom 22 of the vessel.
  • the ventilation opening (s) is (are) preferably provided in the vessel wall 21 and / or in the metering and application device 3.
  • the vessel 2 is preferably made of glass.
  • the dosing and application device 3 and the riser 11 are preferably made of a plastic that is inert to the peptide-containing dispersion C.
  • the metering valve 4 can be made of plastic or metal.
  • the nasal adapter 5, the covering cap 7 and the optionally removable base 14 are made of plastic.
  • the trailing piston 9 is preferably made of rubber. The dimensioning of the drag piston 9 is preferably selected such that a reliable sealing of the usable volume 10 against gas, in particular air, and liquid is ensured.
  • the dimensions are chosen so that the frictional force between the drag piston 9 and the inner wall 21 of the vessel is large enough that the drag piston 9 is not displaced when the metering valve 4 is actuated, on the other hand the external air pressure is sufficient, the usable volume 10 by the amount expelled To reduce peptide-containing dispersion C.
  • a certain amount of the dispersion C is filled into the useful volume 10 of the evacuated device 1 with the exclusion of gas.
  • suitable devices on the one hand ensuring the evacuation of the vessel 2 and on the other hand overriding the disposable character of the metering valve 4.
  • the technology required for this is conventional, so that a detailed description of the filling process is dispensed with.
  • the dosing and application device 3 is actuated.
  • the metering and application device 3 in particular the metering valve 4, is actuated by pressure on the flange-like widening 8 of the conical nasal adapter 5.
  • the pressure exerted is transferred to the dispersion C located in the useful volume 10.
  • the dispersion in turn presses on the closure member of the metering valve 4 until the path for the human calcitonin-containing dispersion C into the passage 6 of the nasal adapter 5 is thereby opened.
  • the peptide-containing, in particular human calcitonin-containing, dispersion, in particular solution, located within the useful volume 10 is in this way under
  • the shelf life of the aqueous solution containing human calcitonin is significantly increased by the method and the device according to the invention, in particular the required shelf life of 1 1/2 to 2 years is achieved.
  • the method according to the invention is simple to use and can be carried out using conventional technologies.
  • the device according to the invention is simple, inexpensive and can be produced using conventional production methods.
  • the use of the device is simple and easy to do.
  • the device according to the invention in one of the described embodiment variants for the nasal application of peptide-containing dispersions, in particular for the nasal application of aqueous solutions containing human calcitonin, in order to spare the patient other administration methods which are often perceived as unpleasant.
  • the method according to the invention and the devices according to the invention are not restricted solely to nasal applications or to nasal applicators.
  • the method according to the invention can also be used, for example, in injection devices or other active substance dispensers.
  • the basic idea of the method according to the invention for the stable storage of peptide-containing dispersions is to fill a certain amount of a peptide-containing dispersion with the exclusion of gas into an evacuated useful volume of a vessel such that the boundary surfaces of the useful volume are always the only interfaces for the peptide-containing dispersion form.
  • a device according to the invention suitable for this purpose comprises an approximately cylindrical vessel and an evacuable useful volume arranged inside the vessel for a quantity of the peptide-containing dispersion.
  • the usable volume is sealed gas-tight from the environment. The boundaries of the useful volume are always the only interfaces for the peptide-containing dispersion contained in the useful volume.

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  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Medicinal Preparation (AREA)
EP92810655A 1991-09-05 1992-08-26 Méthode et dispositif pour contenir et administrer une dispersion contenant des peptides Withdrawn EP0531257A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP91810710 1991-09-05
EP91810710 1991-09-05

Publications (1)

Publication Number Publication Date
EP0531257A1 true EP0531257A1 (fr) 1993-03-10

Family

ID=8208875

Family Applications (1)

Application Number Title Priority Date Filing Date
EP92810655A Withdrawn EP0531257A1 (fr) 1991-09-05 1992-08-26 Méthode et dispositif pour contenir et administrer une dispersion contenant des peptides

Country Status (2)

Country Link
EP (1) EP0531257A1 (fr)
JP (1) JPH05192380A (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0737519A2 (fr) * 1995-04-13 1996-10-16 Monturas, S.A. Pulvérisateur à pompe à précompression
WO1997006842A1 (fr) * 1995-08-18 1997-02-27 Pharmasol Limited Applicateur d'aerosol
GB2319485A (en) * 1995-08-18 1998-05-27 Pharmasol Ltd Spray applicator
US6145703A (en) * 1995-08-18 2000-11-14 Pharmaso Limited Spray applicator
WO2001058260A1 (fr) * 2000-02-11 2001-08-16 Bayer Aktiengesellschaft Moyen permettant de lutter contre le carpocapse
WO2009093720A1 (fr) * 2008-01-25 2009-07-30 Canon Kabushiki Kaisha Appareil éjecteur de médicament et son procédé de commande
FR2971775A1 (fr) * 2011-02-23 2012-08-24 Valois Sas Distributeur de produit fluide
CN103706006A (zh) * 2013-12-13 2014-04-09 中山市美捷时包装制品有限公司 一种医用喷雾器

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB959835A (en) * 1961-10-31 1964-06-03 County Lab Ltd Improvements relating to dispensers for viscous liquids
EP0193054A1 (fr) * 1985-02-21 1986-09-03 Ing. Erich Pfeiffer GmbH & Co. KG Distributeur de substances susceptibles de couler
EP0143183B1 (fr) * 1983-10-28 1988-06-08 Ing. Erich Pfeiffer GmbH & Co. KG Distributeur de matières actives
EP0276983A2 (fr) * 1987-01-28 1988-08-03 Unilever Plc Dispensateur à pompe pour fluides visqueux

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB959835A (en) * 1961-10-31 1964-06-03 County Lab Ltd Improvements relating to dispensers for viscous liquids
EP0143183B1 (fr) * 1983-10-28 1988-06-08 Ing. Erich Pfeiffer GmbH & Co. KG Distributeur de matières actives
EP0193054A1 (fr) * 1985-02-21 1986-09-03 Ing. Erich Pfeiffer GmbH & Co. KG Distributeur de substances susceptibles de couler
EP0276983A2 (fr) * 1987-01-28 1988-08-03 Unilever Plc Dispensateur à pompe pour fluides visqueux

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0737519A3 (fr) * 1995-04-13 1997-11-26 Monturas, S.A. Pulvérisateur à pompe à précompression
EP0737519A2 (fr) * 1995-04-13 1996-10-16 Monturas, S.A. Pulvérisateur à pompe à précompression
US6145703A (en) * 1995-08-18 2000-11-14 Pharmaso Limited Spray applicator
GB2319485A (en) * 1995-08-18 1998-05-27 Pharmasol Ltd Spray applicator
AU707525B2 (en) * 1995-08-18 1999-07-15 Pharmasol Limited Spray applicator
GB2319485B (en) * 1995-08-18 1999-09-22 Pharmasol Ltd Spray applicator
WO1997006842A1 (fr) * 1995-08-18 1997-02-27 Pharmasol Limited Applicateur d'aerosol
WO2001058260A1 (fr) * 2000-02-11 2001-08-16 Bayer Aktiengesellschaft Moyen permettant de lutter contre le carpocapse
WO2009093720A1 (fr) * 2008-01-25 2009-07-30 Canon Kabushiki Kaisha Appareil éjecteur de médicament et son procédé de commande
US8607783B2 (en) 2008-01-25 2013-12-17 Canon Kabushiki Kaisha Drug ejecting apparatus and control method thereof
FR2971775A1 (fr) * 2011-02-23 2012-08-24 Valois Sas Distributeur de produit fluide
CN103706006A (zh) * 2013-12-13 2014-04-09 中山市美捷时包装制品有限公司 一种医用喷雾器
CN103706006B (zh) * 2013-12-13 2015-12-23 中山市美捷时包装制品有限公司 一种医用喷雾器

Also Published As

Publication number Publication date
JPH05192380A (ja) 1993-08-03

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