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    • 专利摘要:
    CARTRIDGE AND DEVICE OF MINISTRATION OF UNITARY DOSE OF MEDICINE. A dry powder drug delivery device is described, comprising: a drug container containing a unit dose of powdered drug; a drug delivery set; and optionally an air source.
    公开号:BR112014014594B1
    申请号:R112014014594-6
    申请日:2012-12-14
    公开日:2021-02-17
    发明作者:Robert Nichol Boyes；Philip Wilson Braithwaite
    申请人:Indosys Limited；
    IPC主号:
    专利说明:

    [0001] [001] The present invention relates to a new dry powder drug delivery device, its uses and manufacturing methods.
    [0002] [002] More particularly, the invention relates to a new dry powder drug delivery device, which is suitable for use as, for example, a nasal drug delivery device for administering drugs, for example, for the treatment of a respiratory disorder, and especially for administration of a vaccine or a hormone, such as glucagon, in dry powdered form. The medication delivery device is also suitable for use when administering a medication, for example, in powder form, into an infusion bag, the medication then being administered to the patient, as an infusion of fluids , for example, as an “IV drip” (IV drip).
    [0003] [003] The invention also relates to a new medication carrier cartridge for use in a medication delivery device. BACKGROUND OF THE INVENTION
    [0004] [004] In recent years, drug formulations have been developed in dry powder form, for example, administered by inhalation, or by mixing in a solution for administration via intravenous infusion. Such dry powder formulations include existing compounds reformulated in dry powder form and newly developed compounds used to treat many conditions and diseases.
    [0005] [005] Drug formulations, in dry, inhalable powder form, offer advantages over other forms, such as liquids and tablets, particularly when considering stability and storage.
    [0006] [006] The oral or nasal administration of a drug, using a dry powder drug delivery device, is a particularly attractive method of drug delivery, since such devices can be relatively easy for a patient to use, as well as medication administration for the local treatment of diseases of the respiratory tract and other respiratory disorders, dry powder medication delivery devices have also, more recently, been used to administer drugs into the bloodstream through the nasal passages or the lungs, avoiding thus, for example, the need for injections.
    [0007] [007] An advantage of administering a drug in dry powder form is that very low dosages of the drug can be used. However, in many situations, the disadvantage of using dry powder formulations lies in the complication of effective delivery to the treatment area and / or measurement of very low doses of medication to the patient. The main problem is found in the exact measurement and containment of a unit dose, and subsequent release or administration adequately controlled of the unit dose. This is a significant obstacle for the pharmaceutical industry in the potential development of dry powder formulations for obtaining finished products.
    [0008] [008] Dry powder delivery devices are most commonly known in the form of dry powder inhalers, which range from fixed dose devices, such as Clickhaler®, where the dry powder medicine is stored in a reservoir and measured by the functioning of the device, up to unit dose devices, where the medicine is stored in individual unit doses in capsules (for example, Spinhaler®) or blisters (for example, Diskhaler®). These devices are, in general, complicated and complex in their construction and, although suitable for the intended use for administering medication to the lung, their adaptation for administration to other treatment areas, such as the nasal and / or nasal cavity routes, is generally unsatisfactory.
    [0009] • aspirar um volume específico de fluido de infusão para dentro de uma seringa; • com uma agulha na seringa, injetar solução de infusão em um frasco tampado com borracha contendo a quantidade dosada de substância do fármaco em pó; • misturar a solução de infusão com a substância em pó; • aspirar a mistura em pó ou solução do fármaco de volta para dentro da seringa; • transferir a solução/ mistura da seringa para a solução da injeção de grande volume, normalmente contida numa bolsa de plástico flexível. [009] In addition, for the administration of a dry powdered medicine, by means of an intravenous infusion, the process of mixing a powdered drug in an infusion bag may involve the following steps: • aspirate a specific volume of infusion fluid into a syringe; • with a needle in the syringe, inject the infusion solution into a rubber-capped vial containing the metered amount of powdered drug substance; • mix the infusion solution with the powdered substance; • aspirate the powder mixture or drug solution back into the syringe; • transfer the solution / mixture from the syringe to the large volume injection solution, usually contained in a flexible plastic bag.
    [0010] • o processo pode ser complicado, envolvendo várias etapas; • agulhas são envolvidas para facilitar a injeção para dentro do frasco contendo o fármaco; • o armazenamento pode ser um problema, porque o frasco do fármaco precisa ter capacidade suficiente para acomodar o volume de fluido; • erros de dosagem podem ser gerados no processo de transferência; • a manipulação de fármacos de quimioterapia pode ser complicada através do processo de transferência. [0010] However, there are a number of problems associated with this process: • the process can be complicated, involving several steps; • needles are wrapped to facilitate injection into the vial containing the drug; • storage can be a problem, because the drug bottle needs to have enough capacity to accommodate the volume of fluid; • dosing errors can be generated in the transfer process; • handling chemotherapy drugs can be complicated by the transfer process.
    [0011] [0011] The present invention aims to provide a dry powder drug delivery device that overcomes, or substantially alleviates, problems with conventional inhalation devices and / or infusion devices. In particular, the invention aims to provide a device having a considerably simpler construction than that of known devices. The dry powder drug delivery device of the present invention is also easier to manufacture, assemble and use, in addition to being cheaper to manufacture.
    [0012] [0012] The present invention now described offers a means of measuring a unit dose of dry powder within a container or cartridge, which is easily adaptable to a range of devices designed to suit a diverse range of types of treatment. An advantage of the delivery device of the present invention is that it is able to accurately deliver a fixed dose of a powdered medicine, being easy to operate, inexpensive and disposable.
    [0013] [0013] Another advantage of the present invention is that the dry powder measurement / filling method in the unit dose cartridge or container is capable of being easily dimensioned, from manual filling in the laboratory to mass production.
    [0014] [0014] Furthermore, intranasal dry powder vaccines have recently been developed. There are a number of advantages for intranasal drug delivery, in particular, in the form of dry powder. Giving intranasal drug provides rapid absorption into the bloodstream by absorption through nasal mucus; the possibility of reducing, or eliminating, the management of the vaccine cooling chain during storage and transportation; and the elimination of needles and the possibility of needlestick injuries.
    [0015] [0015] Intranasal vaccination represents an attractive non-invasive alternative to needle-based injection and provides superior protection on mucosal surfaces. However, new formulations and delivery devices are needed to improve efficacy and reduce distribution and cold storage requirements associated with conventional liquid vaccines.
    [0016] [0016] Vaccines formulated as liquids may be subject to chemical degradation, for example, aggregation, denaturation, hydrolysis and oxidation, which can result in their inactivation. Liquid vaccine formulations can also be temperature sensitive: elevated temperatures can increase inactivation, and freezing temperatures can result in ice, which can damage the antigen in the vaccine. Thus, to avoid inactivation, liquid vaccines must often be stored at a temperature of around 2-8 ° C.
    [0017] [0017] How a vaccine is administered can play an important role in its effectiveness. One mode of delivery, non-parental delivery (for example, nasal delivery), can induce and stimulate systemic and mucosal immune reactions. In addition, the nasal mucosa can help fix a virus or other pathogen on the mucosal surface, preventing the pathogen from accessing the deeper tissues and / or decreasing the likelihood of infection altogether.
    [0018] [0018] Another advantage of the delivery device of the present invention is the use of a new medication carrier cartridge. US Patent Application No. 2007/060868 and U.S. Patent No. 6,398,074 describe drug delivery devices that, when triggered, deliver a powdered drug with a generally linear flow. Such devices generally suffer from a lack of de-agglomeration of the powder. This contrasts with the new medicine carrier cartridge, described below, which provides a non-linear path for the powder, helping to de-agglomerate, inter alia. SUMMARY OF THE INVENTION
    [0019] [0019] Therefore, according to a first aspect of the invention, a dry powder drug delivery device is provided, comprising: a medicine container, for example a cartridge, containing a unit dose of dry powdered medicine; a medication dispensing set; and optionally, an air source.
    [0020] [0020] According to another aspect of the invention, the dry powder drug delivery device includes an air source.
    [0021] [0021] The medication container may comprise a unit dose cartridge or drug container, which comprises an elongated member, provided with an insertion cavity, which functions as a medication reservoir and a closure sleeve. Such a container or cartridge is described in more detail below and with reference to figures 7a to 7c of the present document.
    [0022] [0022] An important aspect of the cartridge, comprising an elongated member and a sliding outer sleeve, is that, in use, the powdered medicine is forced to flow in a non-linear path, before being expelled from the delivery device. In effect, the cartridge of that aspect of the invention is such that the powdered medicine is forced to flow, substantially, through at least two angular turns, for example, turning at right angles, that is, a first turning at an angle straight, followed by a second right-angled turn when it is ejected from the release device. Preferably, two angular turns are present. This provides a significant advantage in the efficient de-agglomeration of the powder, while it does not prevent the efficient cleaning of the entire dose of the cartridge drug cavity, with a speed sufficient for the powder to reach its intended target, for example, the nasal cavity. In addition, the elongated member and the sliding outer sleeve provide a safe and simple storage compartment for the powdered medicine, which, when activated, also provides an effective means of de-agglomerating the powder, as previously described herein.
    [0023] [0023] However, while it is preferred that a cartridge comprises an elongated member and a slidable outer sleeve, it will be understood by the person skilled in the art that a variety of known unit dose medicine containers can be suitably used in the medicine delivery device. dry powder. Thus, for example, the unit dose dry powder formulation may comprise a pre-packaged capsule or blister, where each contains an individual dose, generally in the form of a powder dose, which has been measured accurately and consistently. .
    [0024] [0024] A medication dispensing set generally comprises a body and a mouthpiece. More particularly, the drug dispensing assembly comprises a body, a mouthpiece and an airway, for example, two airways, an inlet and an outlet. For an intranasal delivery device, the mouthpiece is desirably sized and formed to be suitable for placement inside a patient's nostril. While it is understood by the person skilled in the art that the drug dispensing set can also be designed to be suitable for oral delivery, such as an inhaler for delivery to the lungs (respiratory tract). For intravenous administration, for example, through an infusion bag, the medication dispensing set comprises a body, a mouthpiece, an inlet and an outlet, wherein the outlet comprises means for connecting to a fluid bag, for example , an infusion bag.
    [0025] [0025] The airway may comprise a release pump, for example, it may comprise a syringe. Such a syringe may, for example, comprise a syringe with conventionally known property, for example, a disposable syringe, or it may comprise a conventionally known means for ejecting an air flow, for example, an insufflator or other apparatus suitable for blowing air or gas after activation, such as a cylinder and piston, bellows, a compressible bulb, or a source of gas or compressed air, such as a compressed air reservoir or a compressed air system equipped with a suitable pressure control device and volume.
    [0026] [0026] Alternatively, in another embodiment for use as a nasal drug delivery device, the syringe can be replaced with a tube, thus formed, so that the patient can place the open end between his lips and blow the drug dry powder for your nasal cavity.
    [0027] [0027] In yet another embodiment, the syringe can be replaced with a straw and the mouthpiece can be replaced with an alternative mouthpiece, thus formed in order to facilitate the user to be able to suck the liquid through the device by discharging the drug dry powder into the liquid. It will be understood by the person skilled in the art that the powdered medicament can be discharged in any suitable liquid, for example, an aqueous vehicle, including, but not limited to, a gel.
    [0028] [0028] In particular, with the intranasal delivery device of the invention, it is desirable that the speed and volume of air, which passes through the device, be controlled. Therefore, it may be desirable to use a dedicated air speed / volume control system, instead of a regular syringe. Such a dedicated air speed / volume control system may comprise a dedicated (air) pump. Alternatively, a dedicated air speed / volume control system may comprise a rupture diaphragm or a release valve. In addition, the use of a resilient and flexible diaphragm valve element, or rupture diaphragm, can be advantageous in that, through the positioning of a dry dispersible powder material, for example, a medicament material, downstream of a resilient and flexible diaphragm valve element, or rupture diaphragm, the realization with which the valve element flexes or diaphragm ruptures, will produce a rapid decrease in air pressure upstream of the valve or diaphragm through the air path in the device, which disperses and / or de-agglomerates the material.
    [0029] [0029] When the delivery device comprises a dry powder inhaler, for example, an intranasal inhaler, an air source may be provided, although it is understood by the person skilled in the art, that the air source may comprise a syringe. In addition, a rupture diaphragm or release valve can, for example, be placed between the air source and the release device (intranasal), so that when the diaphragm ruptures or bursts, or the release valve opens , at a certain predetermined air pressure, the speed of air passing through the device will unblock it very effectively. For example, it is possible for air from a rupture diaphragm to disperse the powder twice as far as the same volume of air from a syringe being compressed quickly by hand.
    [0030] [0030] Thus, according to the invention, there is provided a method for producing an aerosol from a dry powder, which comprises positioning a disposable dry powder material, for example, a medicament material, downstream of an insulating element. resilient and flexible diaphragm valve or rupture diaphragm; where to cause the valve element to flex, or the diaphragm to rupture, will produce a rapid decrease in air pressure upstream of the valve or diaphragm through the air path in the device, which disperses and / or de-agglomerates the material.
    [0031] [0031] The flexible and resilient delivery valve may comprise a resilient and flexible diaphragm valve element. Such a valve element is described in EP 0 160 336. European Patent Application No. 0 160 336 describes a flexible container, for example, a spray gel container, including a self-sealing release valve. The valve generally comprises a flexible resilient diaphragm, with at least one groove. This valve is closed until pressure is applied to the flexible container, which causes the valve to assume a convex shape and the groove to open. The self-sealing valve, described in the prior art, is known to be used, for example, in containers for storage and administration of viscous gels and / or liquids, since the resilient valve element will close when the pressure is removed from the walls of the release container. Such a valve is ideally suited for release devices that are reversed in use.
    [0032] [0032] Thus, the preferred valve comprises a concave, elastically deformable part, with its optionally impermeable perimeter, fixed through a discharge orifice. The valve, which will generally be self-sealing, can be fixed through an orifice, so that it is in a closed position. The valve can be placed in an arrangement, by which it is concave inwards, or, alternatively, it can be concave outwards, when in the closed position. The concave-shaped part of the valve can include at least one substantially linear groove that extends through the thickness of the wall, comprising the concave part of the valve. The valve requires the reach of a limit opening pressure, in order to reverse the concave position at rest, in order to dispense the material. When opened, the valve will generally move to a convex arrangement, so the valve may have an outward-facing convex surface or an inward-facing convex surface when opened.
    [0033] [0033] The circumferential wall of the valve element may be provided with a plurality of circumferential bubbles spaced on the inner surface of the wall. The bubbles are especially advantageous in the embodiment, in which the valve is in a concave position for the interior, at rest, and in a convex position for the interior, when opened. Thus, when the valve is forced into an open position, the bubbles can react against the distortion of the side wall and, therefore, propel the valve back to a closed position. Thus, a pressure differential is essential to reopen the valve element of the invention.
    [0034] [0034] Many different materials can be used as the diaphragm valve element. The material may vary, depending on the nature of the material intended to pass through the valve. It is of utmost importance that it is flexible, resilient and / or elastomeric. The material can preferably be non-porous. More particularly, when the valve mechanism is used, in such a way that it is driven by a gas pressure differential, then the membrane material is non-permeable to gas. Thus, plastic materials are well suited for use as a valve element material, an elastomer, such as silicone rubber, being an example of such a plastic material. Other examples include, but are not limited to, polyvinyl chloride, urethane, ethylene vinyl acetate and styrene-butadiene copolymer.
    [0035] [0035] It will be understood by the person skilled in the art, that the flexible and resilient release valve can be replaced by a rupture diaphragm (not shown). Such a rupture diaphragm can comprise a frangible membrane, for example, a plastic membrane, which is adapted to rupture under pressure. Such a rupture diaphragm assembly is especially suitable for use with a disposable device, since it would be suitable for a single operation. This contrasts with a device, which comprises a resilient and flexible release valve element, which can be operated again and again.
    [0036] [0036] In one embodiment, the dry powder drug delivery device comprises a drug delivery device, for example, a nasal inhaler. However, in another embodiment, drug carrier is used in a device to facilitate the application of the drug in the form of dry powder, through an air flow to the vagina or rectum, such a device can be equipped with a feature for dilate the vagina or rectum.
    [0037] [0037] The dry powder drug delivery device, in accordance with this aspect of the invention, may be suitable for administering a variety of medications and may be suitable for use in the treatment of a variety of disorders.
    [0038] [0038] So, for example, for use as an inhaler, for example, an inhaler for drug delivery by the oral route, or a nasal powder drug delivery device, for example, a nasal inhaler, a variety of medications can be taught. Such drugs are generally suitable for the treatment of asthma, COPD (chronic obstructive pulmonary disease) and respiratory infections. Such drugs include, but are not limited to [beta] 2-agonists, for example, fenoterol, formoterol, pyrbuterol, reproterol, rimiterol, salbutamol, salmeterol and terbutaline; non-selective beta stimulants, such as isoprenaline; xanthine bronchodilators, for example, theophylline, aminophylline and choline theophyllinate; anticholinergics, for example, ipratropium bromide; mast cell stabilizers, for example, sodium cromoglycate and ketotifen; bronchial anti-inflammatory agents, for example, nedocromil sodium; and steroids, for example, beclomethasone dipropionate, fluticasone, budesonide, flunisolide and ciclesonide, and isomers and / or their salts or derivatives.
    [0039] [0039] Specific drug combinations, which may be mentioned, include combinations of steroids, such as beclomethasone dipropionate and formoterol; beclomethasone dipropionate and salmeterol; fluticasone and formoterol; fluticasone and salmeterol; budesonide and formoterol; budesonide and salmeterol; flunisolide and formoterol; and flunisolide and salmeterol. It is also within the scope of this invention to include combinations of one or more of the aforementioned steroids, with one or more of the aforementioned β2-agonists.
    [0040] [0040] However, there is a growing interest in pulmonary or intravenous medication administration, due, among other things, to the rapid onset of its effective effect. Thus, other drugs, which may be mentioned include, systemically active materials, such as protein compounds and / or macromolecules, for example, hormones and mediators, such as insulin, glucagon, human growth hormone, leuprolide and alpha interferon, growth factors , anticoagulants, immunomodulators, cytokines and nucleic acids. Other drugs, which may be mentioned, are those for the treatment of neurological disorders, such as Parkinsonism, such as, levodopa, carbidopa, benserazide, selegiline, tolcapone, entacapone, bromocriptine, lisuride, pergolide, ropinirole and cabergoline; or migraine, such as sodium divalroex, ergotamine, methysergide, metoprolol, propranolol, zolmitriptan, vigabatrin, clonidine, ganaxolone, lysine acetylsalicylate, sumatriptan, naratriptan, timolol, almotriptan, cyproeptadine, diizizarotizine, dyizizarotizine, timizizarotizine, dyizizamine eletriptan, prochloroperazine, nadolol and frovatriptan. In addition, drugs for the treatment of sexual dysfunction can be mentioned. Such disorders include erectile dysfunction, where treatments include administration of phosphodiesterase type 5 (PDTE5) inhibitors, such as tadalafil, vardenafil and sildenafil; and premature ejaculation, where treatments include administration of serotonin reuptake inhibitors, such as dapoxetine.
    [0041] [0041] However, a particular aspect of the present invention provides the dry powder drug delivery device, as previously described, as a nasal dry powder drug delivery device. A nasal powder dry drug delivery device, in accordance with this aspect of the invention, may be suitable for the delivery of any of the medications previously described.
    [0042] [0042] Another particular aspect of the present invention provides the drug delivery device, as described herein, as an intravenous delivery device or, more particularly, a device for measuring a desired dose of drug suitable for intravenous administration, for example example, through a fluid bag, for example, an infusion bag.
    [0043] [0043] An important use of the delivery device of the present invention is for the delivery of an emergency therapy. Intranasal or intravenous drug delivery routes can provide rapid drug absorption into the bloodstream. For example, the intranasal route may also provide a less invasive route of drug delivery, as compared to some other routes, such as intravenous or intramuscular injection. Such rapid and effective administration of the drug can be useful in the treatment of crisis situations, such as pain, seizures, severe hypoglycemic reactions, etc ...
    [0044] [0044] The delivery device of the present invention proves to be especially advantageous in administering a medication in an emergency situation, for example, when the patient is unconscious. The nasal delivery device of the invention is especially useful in situations where medical assistance is not available. Such a specific treatment is the intranasal administration of a therapeutically effective amount of glucagon to a diabetic, who is experiencing a severe hypoglycemic reaction. Glucagon is a hormone, which causes the liver to release glucose into the blood and is used to rapidly increase blood sugar levels in diabetics with hypoglycaemia (reduced blood sugar). Glucagon is usually supplied in powder form and given as an injection, either into a vein, a muscle in the arm or leg, or under the skin, as directed generally to an unconscious patient. The glucagon powder must first be dissolved in a diluent fluid and must be used immediately after mixing.
    [0045] Therefore, according to a particular aspect of the present invention, a method of administering glucagon to a patient is provided, which comprises the use of a drug delivery device, as described herein, especially the use of a nasal device of dry powder medicine release.
    [0046] [0046] Another category of patients, for whom intravenous or intramuscular injection may be problematic, is that of infants and young children, therefore, the use of the delivery device of the present invention, as an intranasal, oral or rectal drug, can be beneficial.
    [0047] [0047] In addition, when used as an inhaler, for example, an oral inhaler and especially a dry powdered medicine delivery device, the drug delivery device, as previously described here, can be used appropriately for administration one or more dry powder vaccines.
    [0048] [0048] Dry powder vaccine compositions for intranasal administration are described in International Patent Application No. WO 2011/129120. Therefore, a dry powder vaccine for use in combination with a drug delivery device, such as a dry powder drug delivery nasal device of the present invention, can be useful for the prevention and / or treatment of infection by any virus. .
    [0049] [0049] However, it will be understood by the person skilled in the art that the dry powder medications mentioned herein can be administered using the delivery device of the present invention, to deliver a dry powder medicament, for example, to an intravenous infusion bag.
    [0050] [0050] In another embodiment, a drug carrier can be used in a device to facilitate the application of the drug in the form of dry powder, by discharging the powder into a gel for administration to a body orifice.
    [0051] [0051] In yet another embodiment, a drug carrier can be used in a device to facilitate the application dermally or transdermally of the drug in the form of dry powder, by means of a gel applicator.
    [0052] [0052] It will be noted that the above description may apply to the treatment of animals as well as humans.
    [0053] [0053] The preferred unit dose medicine container, for example, a cartridge, for use in combination with the dry powder medicine delivery device of the present invention, is new in itself.
    [0054] [0054] The invention further provides a method for delivering a drug, for example, a dry powdered drug, to a patient, which comprises using a dry powdered drug delivery device, as previously described herein.
    [0055] • o corpo principal é primeiro ligado a uma bolsa de fluido (diretamente ou através de um tubo de ligação). O fluido é impedido de fluir para fora da bolsa através da utilização de grampo ou torneira de fechamento; • uma seringa é ligada na extremidade oposta do corpo principal; • o transportador de medicamento ou fármaco é deslocado para sua posição aberta; • o grampo/ torneira de fechamento é aberto, permitindo que fluido flua para fora da bolsa; • o êmbolo da seringa é puxado para trás e, no processo de arrastar o fluido para fora da bolsa de fluido, descarrega e mistura o pó dentro do fluido; • o êmbolo da seringa é comprimido, passando a mistura de pó/ fluido de volta, através do transportador de fármaco/ corpo principal, para dentro da bolsa de fluido. [0055] When the method, according to that aspect of the invention, comprises administering intravenous drug, the method may include a process of mixing a powdered medicine in an infusion bag, for example, an intravenous infusion bag. An example of the process may involve, by way of illustration only, the following steps: • the main body is first connected to a fluid bag (either directly or via a connecting tube). The fluid is prevented from flowing out of the bag through the use of a clamp or stopcock; • a syringe is attached to the opposite end of the main body; • the medication or drug carrier is moved to its open position; • the closing clamp / tap is opened, allowing fluid to flow out of the bag; • the syringe plunger is pulled back and, in the process of dragging the fluid out of the fluid bag, it discharges and mixes the powder into the fluid; • the syringe plunger is compressed, passing the powder / fluid mixture back through the main body / drug carrier into the fluid bag.
    [0056] [0056] Fluid can be prevented from leaking out of the device, by a seal, which has a circumferential sealing element to seal against a sealing box inside the main body, and a face sealing element to seal against the face of the medication carrier.
    [0057] [0057] The invention further provides a method of treating a patient with a disorder, which comprises administering a drug using a drug delivery device, as previously described herein.
    [0058] The method of treatment, according to that aspect of the invention, may comprise the administration of one or more of the therapeutically active agents described herein. However, a method for delivering a vaccine, for example, a dry powder vaccine, to a patient is especially provided.
    [0059] [0059] More particularly, the invention provides a method of treating a patient, which comprises administering a therapeutically effective amount of glucagon to a diabetic undergoing a hypoglycemic reaction.
    [0060] Therefore, according to another aspect of the present invention, there is provided a unit dose medicine container, which comprises an elongated member provided with an insertion cavity; and a sliding outer sleeve.
    [0061] [0061] The outer sliding sleeve is able to slide to close or to show a little or the entire cavity. As previously described, the unit dose medicine container is generally suitable for delivering a dry powdered medicine, for example, for a dry powder nasal inhaler or an intravenous infusion bag.
    [0062] [0062] Although the elongated member and the sliding outer sleeve can comprise a variety of suitable materials and can be made by a variety of methods, the member and sleeve can optionally comprise the same material, for example, a plastic material.
    [0063] [0063] Desirably, the elongate member comprises a suitable first plastic material and the sliding sleeve comprises a second alternative plastic material. The preferred device, i.e., comprising first and second plastic materials, can be manufactured by a variety of methods, preferably including a method known as two-stroke molding. The two-stroke molding method is a molding process, which allows the combined components, that is, the limb (first plastic material) and the sleeve (second plastic material) to be produced in a single machine cycle without subsequent assembly. Such a method results in significant savings.
    [0064] [0064] The term "suitable" plastic material, as described above, is intended to mean, for example, the first and second plastic material, which do not bond to each other. The lack of connection between the first and second plastic material allows the sleeve to slide over the elongated member.
    [0065] Thus, according to another aspect of the invention, a two-stroke molding method of a medicine container is provided, comprising an elongated member, comprising a suitable first plastic material and the sliding sleeve comprising a second alternative plastic material .
    [0066] [0066] The unit dose medicine container, as previously described here, is advantageous in that, among other things, it is easy and economical to manufacture and can be easily filled on individual bases, or by moving quickly on a production line. A filling method is described in the specific embodiments of this document.
    [0067] [0067] In accordance with another aspect of the invention, a dry powder drug delivery device kit is provided, comprising: a medicine container, for example a cartridge, containing a unit dose of dry powdered medicine; a medication dispensing set; and optionally, an air source.
    [0068] [0068] In one aspect of the invention, the kit comprises an air source. The air source of the kit, as described above, may comprise a delivery pump, such as a syringe or bellows, etc.
    [0069] [0069] The kit, according to that aspect of the invention, can optionally include a dry powder inhaler. Alternatively, the kit can optionally include an intravenous infusion bag.
    [0070] [0070] The invention will now be described, by way of example only and with reference to the accompanying drawings, in which Figure 1a is a perspective view of the drug delivery device of the invention; Figure 1b is a cross-sectional view of the drug delivery device; Figure 1c is a cross-sectional view of the drug delivery device, with the dry powdered drug present; Figure 2a is a perspective view of the drug delivery device in the charged position; Figure 2b is a cross-sectional view of the drug delivery device in the loaded position, with the dry powdered drug present; Figure 2c is a cross-sectional view of the drug delivery device being actuated; Figure 3 is a cross-sectional view of the drug delivery device employing a bellows equipped with a release valve; Figure 4a is a perspective view of a valve of the invention, in the closed position; Figure 4b is a cross-sectional view of a valve of the invention, in the closed position; Figure 5a is a perspective view of a valve of the invention in the open position; Figure 5b is a cross-sectional view of a valve of the invention, in the open position; Figures 6a and 6b are a perspective view of a valve of the invention, illustrating the bubbles on the valve; Figure 7a is a cross-sectional view of the unit dose medicine container, in the open position; Figure 7b is a cross-sectional view of the unit dose medicine container, in the closed position; Figure 7c is a side view of the unit dose medicine container, in the closed position; Figures 8a to 8d are schematic representations of the unit dose medicine container being filled; Figures 9a and 9b are schematic representations of the cross section of the unit dose medicine container being filled; Figures 10a and 10b are schematic representations of the unit dose medicine container being filled by an alternative filling method; Figure 11a is a cross-sectional view of the drug delivery device for use in the infusion, the device being in the closed position; and Figure 11b is a cross-sectional view of the drug delivery device for use in infusion, with the device in the open position.
    [0071] [0071] Referring to Figures 1a to 1c, 2a to 2c and 7a to 7c, a dry powder medicine delivery device 1 comprises a medicine container 2, which contains a unit dose of dry powder medicine 12, a medication dispensing set 3 and, optionally, a syringe 4. Release set 3 comprises a body 5, a nozzle 6 and airways 7 and 8. The medication container 2 comprises a member 9, a cavity 10 and a sleeve 11.
    [0072] [0072] To administer a vaccine with dry powdered medicine, a user (patient or doctor) connects a syringe 4, first extending the syringe 4 to its open position (required capacity), to the release set 3. The nozzle 5 is then compressed towards syringe 4 and, in doing so, pushing member 9 through sleeve 11, to align cavity 10 with airways 7 and 8. Nozzle 6 is inserted into the patient's nostril (not shown) and the syringe 4 is compressed, forcing air through airways 8 and cavity 10, discharging the powdered medicine 12 through airways 7 into the patient's nasal cavity (not shown).
    [0073] [0073] The device, in its preferred embodiment, is a single-use device, the device can therefore be a disposable device, which is discarded after use.
    [0074] [0074] Referring to Figures 7a-c, the unit dose drug container 2, or cartridge, comprises a member 9, into which a cavity 10 is inserted; a sleeve 11 is positioned on the member 9. The member 9 is produced from a suitable polymer and the sleeve 11 is produced from a suitable alternative polymer, by a method known as two-stroke molding; this molding process allows the combined component (member 9 and sleeve 11) to be produced in a single machine cycle, without any subsequent assembly, producing significant savings.
    [0075] [0075] Referring to Figure 3, the body 5 is modified to incorporate the functionality 5a to house the release valve 32 retained by the collar 33 and also retaining the bellows 31; when the bellows 31 are compressed enough to generate the necessary pressure, the valve 32 opens and releases air at high speed into the airway 8.
    [0076] [0076] With reference to Figures 4a and 4b, a diaphragm valve (101) comprises a circular peripheral flange (102) around a concave valve member (103). The flange is connected to an annular part (104). The concave valve member (103) comprises a flexible material and is provided with a groove (105) or a pair of grooves in its body. The illustrated version shows a pair of grooves in the shape of a cross, although it can be appreciated that a variety of groove arrangements may be suitable for the invention to operate satisfactorily. The concave valve member (103) is provided with a release surface (106) and a non-release surface (107). Generally, the release surface (106) is the upper surface and the non-release surface (107) is the lower surface.
    [0077] [0077] Referring to Figures 5a and 5b, when the valve (101) is actuated, pressure is applied directly or indirectly to the non-releasing surface (107) of the valve member (103). This causes the concave valve member (103) to flex and assume a concave shape. The groove (105) opens to generate a hole (108).
    [0078] [0078] Referring to Figures 6a and 6b, the valve member of the present invention is provided with a plurality of spaced circumferential bubbles (112) on the inner surface (113) of the wall (104) of the valve member (103). When the valve is forced into an open position, the bubbles (112) react against the distortion of the side wall and, therefore, propel the valve back to a closed position. Thus, a pressure differential is essential to reopen the valve member of the invention.
    [0079] [0079] Referring to Figures 7a to 7d, 8a and 8b, the medication container 2 (member 9, cavity 10 and sleeve 11) is loaded into a barrel 13 of a filling mechanism or device 14. In Fig.7a , the upper surface of the member 9 has a radius to correspond to the radius of the drum 13, the drum 13 is rotated to align the cavity 10 in the member 9 (Fig. 7b) with the funnel 15, powdered medicine 12 contained in the funnel 15 fills the cavity 10. In Fig. 5c, the drum 13 is further rotated, the surface 16 of the drum 13 closes the funnel 15, the surface 16 of the drum box 17 closes the cavity 17, retaining the powder.
    [0080] [0080] The member 9 is then pushed, through the sleeve 11, so that the sleeve 11 covers the cavity 10 (note, shown as schematic of the position b and c in Fig. 7.). The drum 13 is further rotated to facilitate the removal of the filled sub-assembly 3.
    [0081] [0081] It will be appreciated that the above description is limited to describing the progress of a subset 3 through the filling mechanism, in practice, the drum 13 will facilitate a number of subsets 3 at a time, in a continuous process.
    [0082] [0082] Referring to Figures 10a and 10b, in another embodiment of a filling method and device, subset 3 is loaded onto a disc 18. The upper surface of member 9 is flat (not shown), the disc 18 is rotated to align the cavity 10 in the member 9 with the funnel 19, the powdered medicine 12 contained in the funnel 19 fills the cavity 10. The disk 18 is further rotated and the surface of the disk 18 closes the cavity 10, retaining the medicine powder 12. The member 9 is then pushed through the sleeve 11, so that the sleeve 11 covers the cavity 10. The disk 18 is further rotated to facilitate the removal of the filled subset 4.
    [0083] [0083] The above two descriptions of filling methods and devices are by way of example only, it will be appreciated that those skilled in the art will identify variations to these basic descriptions, for example, by adding means of automation.
    [0084] [0084] Referring to Figures 11a and 11b, the medication device 20 for use in infusion is assembled from four parts, a main body assembly 21, a drug carrier (dry powder) 22, a cover sleeve of the drug well 23 and a sealing component 24.
    [0085] (a)o corpo principal 21 e o selo 24; e (b)o transportador de fármaco 22 e manga de cobertura 23. [0085] These four parts are desirably assembled as two subsets: (a) main body 21 and seal 24; and (b) the drug carrier 22 and cover sleeve 23.
    [0086] [0086] The main body assembly 21 is a release assembly comprising a body 25, a nozzle 26 and fluid / powder channels 27 and 28. The nozzle 26 is provided with lockable ends 29 and 30. In the embodiment shown, end 29 comprises a standard male luer lock and end 30 comprises a standard female luer lock.
    权利要求:
    Claims (13)
    [0001]
    Dry powder drug delivery device (1) comprising: a medicine container (2) containing a unit dose of dry powdered medicine (12); a medication dispensing set (3); and optionally, an air source; wherein said medicine container (2) comprises an elongated member (9) provided with an insertion cavity (10) that functions as a medicine reservoir and the container (2) provides a non-linear path for the flow of the medicine in powder (12); CHARACTERIZED by the fact that the medicine container (2) comprises a sliding closing sleeve (11) capable of sliding to close or reveal part or all of the cavity (10).
    [0002]
    Dry powder drug delivery device (1) according to claim 1, CHARACTERIZED by the fact that the device includes an air source.
    [0003]
    Dry powder medication delivery device (1) according to claim 1 or 2, CHARACTERIZED by the fact that the air source is a delivery pump.
    [0004]
    Dry powder medication delivery device (1) according to any one of claims 1 to 3, CHARACTERIZED by the fact that the medication dispensing set (3) generally comprises a body (5) and a mouthpiece (6 ).
    [0005]
    Dry powder drug delivery device (1) according to any one of claims 1 to 4, CHARACTERIZED by the fact that the drug delivery set (3) comprises an intranasal delivery device.
    [0006]
    Dry powder medicine delivery device (1) according to any one of claims 1 to 5, CHARACTERIZED by the fact that the delivery pump is a syringe (4).
    [0007]
    Dry powder drug delivery device (1) according to any one of claims 1 to 6, CHARACTERIZED by the fact that the air source or delivery pump is a bellows (31).
    [0008]
    Dry powder drug delivery device (1) according to any one of claims 1 to 7, CHARACTERIZED by the fact that the air source or delivery pump is a compressible bulb.
    [0009]
    Dry powder medicine delivery device (1) according to any one of claims 1 to 8, CHARACTERIZED by the fact that the delivery pump comprises an air source and is provided with a rupture diaphragm (101) or valve release.
    [0010]
    Dry powder drug delivery device (1) according to any one of claims 1 to 9, CHARACTERIZED by the fact that the device is an inhaler.
    [0011]
    Dry powder medication delivery device (1) according to claim 10, CHARACTERIZED by the fact that the delivery device is a dry powder nasal inhaler.
    [0012]
    Dry powder drug delivery device (1) according to claim 1, CHARACTERIZED by the fact that the dry powder drug delivery device is for releasing a therapeutically effective amount of glucagon to a diabetic experiencing a reaction hypoglycemic.
    [0013]
    Dry powder drug delivery device (1) according to any one of claims 1 to 12, CHARACTERIZED by the fact that the device is suitable for the delivery of one or more dry powder vaccines.
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    同族专利:
    公开号 | 公开日
    DK2790758T3|2017-11-20|
    JP6218747B2|2017-10-25|
    ES2644922T3|2017-12-01|
    EP2790758A2|2014-10-22|
    EP2790758B1|2017-08-09|
    US9795773B2|2017-10-24|
    CN104159633B|2018-10-12|
    WO2013088112A2|2013-06-20|
    IN2014DN06108A|2015-08-14|
    BR112014014594A2|2017-06-13|
    CA2858997C|2020-03-31|
    CA2858997A1|2013-06-20|
    CN104159633A|2014-11-19|
    WO2013088112A3|2013-10-03|
    US20140364837A1|2014-12-11|
    JP2015500116A|2015-01-05|
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    法律状态:
    2018-12-04| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|
    2019-11-19| B06U| Preliminary requirement: requests with searches performed by other patent offices: suspension of the patent application procedure|
    2020-12-01| B09A| Decision: intention to grant|
    2021-02-17| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 14/12/2012, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    GBGB1121683.5A|GB201121683D0|2011-12-16|2011-12-16|Dry powder medicament unit dose packaging and delivery device|
    GB1121683.5|2011-12-16|
    GB1208854.8|2012-05-18|
    GBGB1208854.8A|GB201208854D0|2012-05-18|2012-05-18|Medicament unit dose packaging and delivery device|
    PCT/GB2012/000907|WO2013088112A2|2011-12-16|2012-12-14|Medicament unit dose cartridge and delivery device|
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