Drug containing device for solid oral preparation and oral administration delivery device containing the same

Abstract

The present invention discloses a drug containing device for solid oral preparations and an oral drug delivery device containing the same. The drug containing device includes a filter component and a support component. The filter component and the support component cooperate with each other to form a space for carrying drug particles or multiple pills. The filter component has one or more channels that allow liquid to pass through; the channels are distributed in an intricate and cross-sectional manner inside the filter component, and / or a water-soluble polymer material layer is provided on the filter component. Alternatively, the drug containing device is a cylindrical structure with an opening at the top and a screen at the bottom. A water-soluble polymer material layer is provided on the inner surface of the screen, and the inner cavity of the cylindrical structure above it is used to accommodate drug particles or multiple pills. The drug containing device of the present invention can overcome the problems of leakage of drug particles or multiple pills and large fluid resistance during sipping.

Description

Technical Field

[0001] The present invention relates to the field of medical devices, and in particular to a drug containing device for solid oral preparations and an oral drug delivery device containing the same. Background Art

[0002] Tablets and capsules are the most convenient and acceptable oral dosage forms. However, some patients, especially children and the elderly, usually have difficulty swallowing large-sized tablets and capsules; some patients are unwilling to take such drugs due to unacceptable taste. Therefore, the prior art proposes various drug delivery devices that can facilitate the swallowing of large-sized tablets and capsules and minimize the patient's perception of the dosage and taste. Among the various drug delivery devices, there are drug containing components that can contain and store drugs. The following patents and applications related to drug containing components of sipping devices are incorporated herein by reference.

[0003] EP 0383503 A1 describes an improved device in which the drug containing component is a screen having a surface area greater than the cross-sectional area of ​​the inner cavity of the tube, which is used to retain and position a unit dose of therapeutic agent in the tube, and the device is adapted to deliver the dose through the tube by liquid flow through the tube by the patient's normal sipping action.

[0004] US Patent 6096003 describes a sipping device, in which the drug containing component is a plug, which can be used to contain active drug ingredients and drive the plug to slide upward in the lumen through liquid, thereby completing the delivery of the drug.

[0005] US Patent No. 6,109,538 discloses a sipping device, the receiving part of which is a pair of screens with rectangular grids, which are arranged in a tube cavity to restrict the seasoning object.

[0006] US Patent 6333050 B2 describes a sipping device, in which the drug receiving component of the device is a one-way valve, which is used to receive drugs when in a non-sipping state and deforms in a sipping state to allow liquid to pass through.

[0007] US patent 8334003 B2 describes a sipping device comprising an elongated tubular member having a pair of filter means at each end of the tubular member to retain flavouring particles within the filter means so that flavouring agents can be introduced into a normal beverage by normal suction.

[0008] US Patent 6224908 B1 describes a delivery device for active pharmaceutical ingredients with a fluid controller. The fluid controller is a porous plug with low friction with the tube wall, which contains the drug in a non-sip state, and accelerates the delivery of the drug to the patient's mouth under the push of the fluid during sip.

[0009] The drug containing parts involved in the above patents will cause many problems in practical application. It is well known that the particles or pellets containing API prepared by wet granulation, dry granulation, extrusion spheronization, melt granulation and other processes generally have a relatively wide particle size distribution, including particles or pellets much larger than the average particle size, and fine powder particles and pellets much smaller than the average particle size. Therefore, for the function of the drug containing part, on the one hand, it is required that the liquid can pass through the drug containing part smoothly with little resistance, so that the patient does not have to sip effortlessly; at the same time, it is required that the aperture of the drug containing part is smaller than the diameter of all particles or pellets to ensure that the particles or pellets will not leak through the drug containing part. These two requirements are contradictory in themselves. The aperture must be large enough to ensure that the resistance to liquid passing through is small; but the larger the aperture, the greater the probability of leakage of particles and pellets with smaller particle sizes. This limits the scope of application. Materials containing particles or pellets with a particle size less than or equal to the aperture of the drug containing part cannot use this device unless they are manually screened, which reduces the yield and increases the cost. Summary of the invention

[0010] The technical problem to be solved by the present invention is to overcome the defects of the prior art devices for promoting drug swallowing, such as leakage of drug particles or multiple pills and large fluid resistance during sip, and provide a drug containing device for solid oral preparations and an oral drug delivery device containing the same. The drug containing device of the present invention is used as a whole with a straw when in use, and is used to contain particles or multiple pills containing active drug ingredients with a particle size greater than, equal to or less than the aperture of the drug containing device.

[0011] The inventors of the present invention discovered at the beginning of research and development that reducing liquid resistance and reducing drug leakage are theoretically opposite propositions and it is difficult to strike a balance. Therefore, the technical difficulty of the present invention lies in finding a reasonable solution that can ensure that the liquid resistance is small while ensuring that the carried particles and multi-pills do not leak.

[0012] From a mechanistic point of view, the present invention allows for the accommodation of drug particles or multiple pills with a particle size less than or equal to the pore size of the filter component by two mechanisms: one is to retain fine particles in the filter component through irregularly interlaced channels in the filter component, and this filter component is required to have a certain thickness, for example, a thickness of more than 0.5 mm; the other is to form a film on the filter component through a water-soluble polymer material to block the pores of the filter component. When sipping, the polymer material instantly dissolves, water flows through, and drives the drug into the patient's mouth. This mechanism has no requirements for the thickness of the filter component.

[0013] One of the objects of the present invention is to provide a drug containing device for solid oral preparations, which includes a filter component and a supporting component for supporting the filter component, the filter component and the supporting component cooperate with each other to form a space for carrying drug particles or multiple pills, and the filter component has one or more channels allowing liquid to pass through; when the thickness of the filter component is greater than 0.5 mm, the channels are distributed in an up and down intricate and cross-shaped manner inside the filter component, so that the drug particles or multiple pills cannot pass through.

[0014] The following is a detailed description of the method of setting the channels of the filter component to a vertically interlaced structure:

[0015] In the present invention, the filter element is a common type in the art, preferably a filter membrane. The filter membrane is preferably cylindrical. The thickness of the filter membrane is preferably 0.5 to 20 mm, more preferably 0.5 to 15 mm, and further preferably 0.5 to 10 mm, for example 2 mm.

[0016] That is to say, the filter membrane has a certain thickness, so the pores of the filter membrane are set to a structure that is intricately crossed up and down. It is preferred that the upper and lower surfaces of the filter membrane and the internal pores are all set to an irregular and intricately crossed structure, such as a sponge-like porous structure, or a fluffy structure formed by irregularly stacking and pressing multiple layers of fibers. In this way, even if the particle size of the drug particles or multi-pills is less than or equal to the pore size of the filter membrane, they will not pass directly through the drug containing device like through a screen. Due to the twists and turns and intricate intersections of the filter membrane pores, drug particles or multi-pills with very small particle sizes will accumulate on its surface and inside. When the liquid passes through, the drug particles or multi-pills accumulated on the surface and inside of the filter membrane are delivered into the patient's mouth.

[0017] The following is a detailed description of the material, pore size, and preparation process of the filter component (e.g., filter membrane):

[0018] Among them, the material of the filter membrane is a conventional filter membrane material in the art, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate, cellulose acetate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, glass fiber, nylon, polyether sulfone, polyvinylidene fluoride and polytetrafluoroethylene.

[0019] The shape of the raw material of the filter membrane is conventional in the art, including but not limited to granular, flaky, fibrous, etc.

[0020] The pore size of the filter membrane is conventional in the art, such as 1-500 μm, preferably 20-400 μm, more preferably 40-300 μm, such as 150 μm, 200 μm, 250 μm, 300 μm.

[0021] The diameter of the filter membrane can be conventional in the art. The diameter of the filter membrane is defined as the effective diameter for retaining solids and passing liquids. For design and installation process considerations, if the outermost circle of the filter membrane diameter is pressed in the middle by the upper and lower support components used to fix the filter membrane, for example, a 10mm diameter membrane has 1mm of the edge pressed by the support component, and the effective diameter is only 8mm. The commonly used effective diameter range of the filter membrane is generally 4-20mm, preferably 6-15mm, more preferably 8mm-12mm, for example 10mm.

[0022] The preparation process of the filter membrane is a conventional process in the art, including but not limited to sintering, injection molding, pressing, weaving, etc.

[0023] The structure of the supporting component is described in detail below:

[0024] In the present invention, the supporting component has a conventional meaning in the art, and its function is to support the filter component without affecting the filterability and liquid permeability of the filter component. Its structure is preferably: arranged on the upper and lower surfaces of the filter component, sandwiching the filter component in the middle, that is, sandwiching the filter component in the middle; or wrapping the filter component inside in a cage-like structure.

[0025] In a preferred embodiment of the present application, the support component includes an upper support component and a lower support component, the upper support component and the lower support component can cover each other and clamp the filter component in the middle, and the space above the upper support component and the filter component is used to accommodate drug particles or multiple pills. This structure is similar to a sandwich form.

[0026] In another preferred embodiment of the present application, the support component includes a filter component accommodating component and a drug accommodating component, the filter component accommodating component and the drug accommodating component both have a porous structure end and an open end, the porous structure end has one or more holes that allow liquid to pass through, the open end of the filter component accommodating component and the porous structure end of the drug accommodating component can be covered to form a cavity for accommodating the filter component; the open end of the drug accommodating component is an open tubular structure for accommodating drug particles or pills. Those skilled in the art should understand that the actual function of the filter component accommodating component in this embodiment is to form a cavity with the drug accommodating component for accommodating the filter component, and this structure is also similar to a sandwich form. In addition, the size of the porous structure of the drug accommodating component and the filter component accommodating component does not affect the filterability and liquid permeability of the filter component.

[0027] In another preferred embodiment of the present application, the support component includes a cage-shaped support component with an opening upward and an upper cover matched with the cage-shaped support component, the upper cover is provided with a channel for the circulation of drug particles or multiple pills and liquid, the cage-shaped support component and the upper cover can enclose to form a hollow space and confine the filter component in the space, and the space above the upper cover and the filter component is used to accommodate drug particles or multiple pills. This structure is similar to the form of a cage structure.

[0028] Among them, the material of the supporting component is a conventional material in the field, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride, polytetrafluoroethylene, polyethylene terephthalate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, ceramics, silicon dioxide, and silicone.

[0029] The preparation process of the support component is conventional in the art, including but not limited to sintering, injection molding, etc.

[0030] The following is a detailed description of the forms and types of drug granules or pellets:

[0031] In the present invention, the drug granules or pellets have the conventional meaning in the art, and generally refer to granules, powders or pellets containing active drug ingredients.

[0032] The particle size of the drug particles or pellets is conventional in the art, generally 1-5000 μm, preferably 25-2000 μm, and more preferably 50-1000 μm.

[0033] Preferably, when the particle size of the drug particles or pellets is in the range of 50-1000 μm, the pore size of the filter component is in the range of 40-300 μm.

[0034] The active pharmaceutical ingredients contained in the drug particles or pellets are conventional in the art, including but not limited to one or more of the following: dabigatran etexilate or a pharmaceutically acceptable salt thereof (e.g., dabigatran mesylate), apixaban, rivaroxaban, levodopa-carbidopa, montelukast, lansoprazole, omeprazole, esomeprazole, amoxicillin, clarithromycin, azithromycin, metronidazole, rifampicin, sulfasalazine, acetaminophen, dextromethorphan, doxylamine, pseudoephedrine, diphenhydramine, amphetamine, methylphenidate, deferasirox, ivacaftor, lumacaftor, tacrolimus, diazepam, clobazam, vigabatrin, bosentan, melatonin, biotin, sodium disodium thiosulfate, amlodipine and esmolol.

[0035] The preparation process of the drug granules or pellets includes but is not limited to one or more of the following processes: wet granulation, dry granulation, extrusion spheronization, melt granulation, ion exchange resin granulation, and pellet spraying.

[0036] The second object of the present invention is to provide an oral drug delivery device, which includes the drug containing device described in the first object, and the oral drug delivery device also includes a tubular member, the tubular member has two openings and an inner cavity, one end opening is a first opening, and the other end opening is a second opening, and the inner cavity connects the first opening and the second opening; the drug containing device is externally connected to the free end of the first opening, and the space for carrying drug particles or multiple pills is connected to the inner cavity.

[0037] The following specifically describes the manner in which the drug containing device is externally disposed at the free end of the first opening:

[0038] In this solution, preferably, the drug containing device is placed outside the tubular member and is maintained at the first opening of the tubular member by a fixed sleeve method or a threaded connection method.

[0039] In this solution, particles or pills containing active pharmaceutical ingredients are placed in the cavity of the drug containing device. When in use, one end of the supporting component contacts the liquid, and the liquid is sucked into the tubular component through the filtering component by the suction action. The particles or pills containing active pharmaceutical ingredients enter the tubular component with the liquid and then enter the mouth.

[0040] In this solution, preferably, a top cover for sealing is further provided at the second opening to ensure that after the oral drug delivery device is loaded with drugs, even if the device is bumped or completely inverted during transportation, the drug particles or multiple pills will not leak from the second opening. Furthermore, the oral drug delivery device loaded with drugs can be directly stored or transported after being sealed in an independent outer packaging to play a role in waterproofing and moisture-proofing.

[0041] The structure of the tubular member is described in detail below:

[0042] In a preferred embodiment of the present application, the tubular component is a straight straw. The straight straw preferably has at least one pleated structure. Preferably, the pleated structure has a pair of wings and a turning end; the pleated structure can be stretched or contracted along the axial direction of the tubular component and form turbulence when stretched.

[0043] In another preferred embodiment of the present application, the tubular component has at least two tube segments, which are sealed and connected to each other and can be stretched or contracted axially along the tubular component; when the tubular component is in a stretched state, a turbulence generating component having at least one step structure is formed.

[0044] Among them, when the number of the pipe segments is 3: the inner diameter of the first pipe segment in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe segment, the outer diameter of the second pipe segment is smaller than the inner diameter of the first pipe segment, and each pipe segment can be stretched or contracted axially along the other pipe segments; or, the inner diameter of the first pipe segment, the outer diameter of the second pipe segment, the inner diameter and the outer diameter of the third pipe segment in the direction from the first opening to the second opening gradually decrease, and each pipe segment can be stretched or contracted axially along the other pipe segments.

[0045] Among them, when the number of the pipe segments is 4: the inner diameter of the first pipe segment in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe segment, and the inner diameter of the second pipe segment is the same as the inner diameter of the fourth pipe segment, wherein the inner diameter of the second pipe segment is smaller than that of the first pipe segment, and each pipe segment can be stretched or contracted axially along the other pipe segments; or, the inner diameters of the first pipe segment to the fourth pipe segment in the direction from the first opening to the second opening gradually decrease, and each pipe segment can be stretched or contracted axially along the other pipe segments.

[0046] The third object of the present invention is to provide an oral drug delivery device, which includes the drug containing device described in the first object, and the oral drug delivery device also includes a tubular member, the tubular member has two openings and an inner cavity, one end opening is a first opening, and the other end opening is a second opening, and the inner cavity connects the first opening and the second opening; the drug containing device is arranged in the inner cavity and is close to the first opening, and the space for carrying drug particles or multiple pills is connected to the second opening; the diameter of the first opening is smaller than the minimum diameter of the drug containing device.

[0047] In this solution, by limiting the diameter of the first opening to be smaller than the minimum diameter of the drug containing device, the drug containing device can be maintained in the inner cavity in any manner and will not fall off from the first opening of the tubular member.

[0048] In this solution, preferably, the diameter of the second opening is smaller than the minimum diameter of the drug containing device.

[0049] In this solution, preferably, a top cover for sealing is also provided at the second opening to ensure that after the oral drug delivery device is loaded with drugs, even if it is bumped or completely inverted during transportation, the drug particles or pills will not leak from the second opening.

[0050] In this solution, the specific description of the structure of the tubular component is the same as described in the second part of the purpose.

[0051] A fourth object of the present invention is to provide a drug containing device for a solid oral preparation, the structure of which is structure 1 or structure 2:

[0052] Structure 1: The drug containing device comprises a filter component and a support component for supporting the filter component, the filter component and the support component cooperate with each other to form a space for carrying drug particles or multiple pills, the filter component has one or more holes allowing liquid to pass through; the filter component is also provided with a water-soluble polymer material layer, so that the drug particles or multiple pills cannot pass through;

[0053] Structure 2: The drug containing device is a cylindrical structure with an opening at the top and a screen at the bottom. A water-soluble polymer material layer is provided on the inner surface of the screen. The inner cavity of the cylindrical structure above the water-soluble polymer material layer is used to accommodate drug particles or pills.

[0054] The present solution has a wide range of applications, and is particularly suitable for situations where, in the particle size distribution of the drug particles or pellets, some particle sizes are smaller than or equal to the pore size of the pore channel.

[0055] The following is a detailed description of the structure, material, pore size, and preparation process of the filter component in Structure 1:

[0056] In the present invention, the filter component is of a conventional type in the art, preferably a filter membrane. The filter membrane is preferably a disc-shaped structure. The thickness of the filter membrane is preferably 0.01-0.5 mm, more preferably 0.1-0.3 mm, for example 0.2 mm. In this case, since the thickness of the filter membrane is thin and its function is similar to a screen, when the resistance of the liquid passing through the screen is very small, the drug particles or pills with a particle size less than or equal to the pore size of the filter membrane will leak out from the filter component, therefore, a water-soluble polymer material layer is provided on the filter membrane.

[0057] The material of the filter membrane is a conventional filter membrane material in the art, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate, cellulose acetate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, glass fiber, nylon, polyether sulfone, polyvinylidene fluoride and polytetrafluoroethylene. The shape of the raw material of the filter membrane includes but is not limited to granular, sheet, fiber, etc.

[0058] The shape and structure of the pores in the filter membrane may be regular structures conventional in the art, such as connecting and penetrating the upper and lower surfaces of the filter membrane in a straight line.

[0059] The pore size of the filter membrane is conventional in the art, such as 1-500 μm, preferably 20-400 μm, more preferably 40-300 μm, such as 150 μm, 200 μm, 250 μm, 300 μm.

[0060] The diameter of the filter membrane can be conventional in the art. The diameter of the filter membrane is defined as the effective diameter for retaining solids and passing liquids. For design and installation process considerations, the outermost circle of the filter membrane diameter will be pressed in the middle by the upper and lower support members to fix the filter membrane. For example, a 10mm diameter membrane has 1mm of the edge pressed by the support member, and the effective diameter is only 8mm. The commonly used effective diameter range of the filter membrane is generally 4-20mm, preferably 6-15mm, more preferably 8mm-12mm, for example 10mm.

[0061] The preparation process of the filter membrane is a conventional process in the art, including but not limited to sintering, injection molding, pressing, weaving, etc.

[0062] The following is a detailed description of the configuration of the water-soluble polymer material layer:

[0063] In the present invention, the water-soluble polymer material layer is formed in a conventional manner in the art, preferably by adsorbing, coating or spraying a polymer material solution on the upper surface and / or lower surface of the filter membrane, or immersing the filter membrane in a polymer material solution, and then drying. After drying, the polymer material is dispersed in the membrane pores and membrane material of the filter membrane to form a skeleton with a certain hardness, while blocking the pores of the filter membrane, so that drug particles or pellets smaller than or equal to the pore size of the filter membrane will not leak during storage and transportation.

[0064] Specifically, the structures formed by the water-soluble polymer material layer are preferably the following two: a continuous water-soluble polymer material layer is formed on the upper surface or lower surface of the filter membrane, or the polymer material completely blocks the pores of the filter membrane to form a complete and dense water-soluble polymer material layer (for example, such a structure is formed by using an immersion method); more preferably, a continuous water-soluble polymer material layer is formed only on the upper surface or lower surface of the filter membrane (for example, such a structure is formed by adsorption, coating, or spraying only on a certain surface of the filter membrane); further preferably, a continuous water-soluble polymer material layer is formed on the lower surface of the filter membrane.

[0065] The dissolution time of the water-soluble polymer material layer is preferably less than or equal to 10 seconds, for example, 2 seconds. When in use, the patient places the drug containing device in the liquid and sips it. At the same time, the water-soluble polymer material layer dissolves in a very short time, and the liquid passes through the drug containing device with very little resistance, delivering the drug particles or multiple pills into the patient's mouth. Since the water-soluble polymer material layer dissolves very quickly, the patient cannot feel the change in resistance when using it.

[0066] In order to better shape the polymer material on the surface of the filter membrane, the water-soluble polymer material layer is preferably selected from polymer materials with good water solubility and film-forming properties and small molecular weight, and is formed into a polymer material solution and then shaped through a certain process.

[0067] The molecular weight of the polymer material is preferably 2000-200000, more preferably 2000-100000. The type of the polymer material is preferably selected from one or more of hydroxypropyl methylcellulose, copovidone, hydroxypropyl cellulose, hydroxyethyl cellulose (HEC), povidone, polyethylene glycol (PEG), gelatin, poloxamer, xanthan gum and Eudragit.

[0068] The preparation method of the polymer material solution is a conventional method in the art, and specifically comprises the following steps: uniformly mixing the polymer material with a solvent, wherein the solvent is a conventional solvent in the art that can dissolve the polymer material and is volatile, such as water, ethanol, acetone, etc.

[0069] In the process of forming the water-soluble polymer material layer, the viscosity of the polymer material solution is a key parameter in the forming process, and the viscosity depends on three parameters, the concentration, molecular weight and chemical structure of the polymer. The viscosity range is generally 2 centipoise (cP)-5000 centipoise (cP), preferably 2cP-1000cP. In the process of forming the water-soluble polymer material layer, the weight gain of the polymer material is generally 0.01-60mg / cm 2 , preferably 0.5-30mg / cm 2 , for example 6.4 mg / cm 2 The “weight gain of polymer material” means the weight of the water-soluble polymer material layer formed on each square centimeter of the filter component (such as a filter membrane) or the screen after solidification and drying, and the weight unit is milligrams.

[0070] In a preferred embodiment of the present application, the polymer material solution is a 10% concentration of hydroxypropyl methylcellulose E3 solution.

[0071] The structure of the supporting component in structure 1 is described in detail below:

[0072] In the present invention, the supporting component has a conventional meaning in the art, and its function is to support the filtering component without affecting the filtering property and liquid permeability of the filtering component.

[0073] In a preferred embodiment of the present application, the support component includes an upper support component and a lower support component, the upper support component and the lower support component can cover each other and clamp the filter component in the middle, and the space above the upper support component and the filter component is used to accommodate drug particles or multiple pills. This structure is similar to a sandwich form.

[0074] In another preferred embodiment of the present application, the support component includes a filter component accommodating component and a drug accommodating component, the filter component accommodating component and the drug accommodating component both have a porous structure end and an open end, the porous structure end has one or more holes that allow liquid to pass through, the open end of the filter component accommodating component and the porous structure end of the drug accommodating component can be covered to form a cavity for accommodating the filter component; the open end of the drug accommodating component is an open tubular structure for accommodating drug particles or pills. Those skilled in the art should understand that the actual function of the filter component accommodating component in this embodiment is to form a cavity with the drug accommodating component for accommodating the filter component, and this structure is also similar to a sandwich form. In addition, the size of the porous structure of the drug accommodating component and the filter component accommodating component does not affect the filterability and liquid permeability of the filter component.

[0075] Among them, the material of the supporting component is a conventional material in the field, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride, polytetrafluoroethylene, polyethylene terephthalate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, ceramics, silicon dioxide, and silicone.

[0076] The preparation process of the support component is conventional in the art, including but not limited to sintering, injection molding, etc.

[0077] The following is a detailed description of the cylindrical structure in Structure 2:

[0078] The material and preparation process of the cylindrical structure are the same as those described in the supporting component part.

[0079] The size of the sieve is conventional in the art, for example, 200 μm.

[0080] The following is a detailed description of the forms and types of drug granules or pellets:

[0081] In the present invention, the drug granules or pellets have the conventional meaning in the art, and generally refer to granules, powders or pellets containing active drug ingredients.

[0082] The particle size of the drug particles or pellets is conventional in the art, generally 1-5000 μm, preferably 25-2000 μm, and more preferably 50-1000 μm.

[0083] Preferably, when the particle size of the drug particles or pellets is in the range of 50-1000 μm, the aperture of the filter component in structure 1 or the screen in structure 2 is 40-300 μm.

[0084] The active pharmaceutical ingredients contained in the drug particles or pellets are conventional in the art, including but not limited to one or more of the following: dabigatran etexilate or a pharmaceutically acceptable salt thereof, apixaban, rivaroxaban, levodopa-carbidopa, montelukast, lansoprazole, omeprazole, esomeprazole, amoxicillin, clarithromycin, azithromycin, metronidazole, rifampicin, sulfasalazine, acetaminophen, dextromethorphan, doxylamine, pseudoephedrine, diphenhydramine, amphetamine, methylphenidate, deferasirox, ivacaftor, lumacaftor, tacrolimus, diazepam, clobazam, vigabatrin, bosentan, melatonin, biotin, sodium disodium thiosulfate, amlodipine and esmolol.

[0085] The preparation process of the drug granules or pellets includes but is not limited to one or more of the following processes: wet granulation, dry granulation, extrusion spheronization, melt granulation, ion exchange resin granulation, and pellet spraying.

[0086] The fifth object of the present invention is to provide an oral drug delivery device, which includes the drug containing device described in the fourth object, and the oral drug delivery device also includes a tubular member, the tubular member has two openings and an inner cavity, one end opening is a first opening, and the other end opening is a second opening, and the inner cavity connects the first opening and the second opening; the drug containing device is externally connected to the free end of the first opening, and the space for carrying drug particles or multiple pills is connected to the inner cavity.

[0087] The following specifically describes the manner in which the drug containing device is externally disposed at the free end of the first opening:

[0088] In the present invention, the drug containing device is placed outside the tubular member, and is preferably maintained at the first opening outside the tubular member by a fixed sleeve method or a threaded connection method.

[0089] In this embodiment, particles or pills containing active pharmaceutical ingredients are placed in the cavity of the drug containing device. When in use, one end of the supporting component contacts the liquid, and the liquid is sucked into the tubular component through the filtering component by the suction action. The particles or pills containing active pharmaceutical ingredients enter the tubular component with the liquid and then enter the mouth.

[0090] In the present invention, preferably, a top cover for sealing is also provided at the second opening to ensure that after the oral drug delivery device is loaded with drugs, even if it is bumped or completely inverted during transportation, the drug particles or pills will not leak from the second opening.

[0091] The structure of the tubular member is described in detail below:

[0092] In a preferred embodiment of the present application, the tubular component is a straight straw. The straight straw preferably has at least one pleated structure. Preferably, the pleated structure has a pair of wings and a turning end; the pleated structure can be stretched or contracted along the axial direction of the tubular component and form turbulence when stretched.

[0093] In another preferred embodiment of the present application, the tubular component has at least two tube segments, which are sealed and connected to each other and can be stretched or contracted axially along the tubular component; when the tubular component is in a stretched state, a turbulence generating component having at least one step structure is formed.

[0094] Among them, when the number of the pipe segments is 3: the inner diameter of the first pipe segment in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe segment, the outer diameter of the second pipe segment is smaller than the inner diameter of the first pipe segment, and each pipe segment can be stretched or contracted axially along the other pipe segments; or, the inner diameter of the first pipe segment, the outer diameter of the second pipe segment, the inner diameter and the outer diameter of the third pipe segment in the direction from the first opening to the second opening gradually decrease, and each pipe segment can be stretched or contracted axially along the other pipe segments.

[0095] Among them, when the number of the pipe segments is 4: the inner diameter of the first pipe segment in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe segment, and the inner diameter of the second pipe segment is the same as the inner diameter of the fourth pipe segment, wherein the inner diameter of the second pipe segment is smaller than that of the first pipe segment, and each pipe segment can be stretched or contracted axially along the other pipe segments; or, the inner diameters of the first pipe segment to the fourth pipe segment in the direction from the first opening to the second opening gradually decrease, and each pipe segment can be stretched or contracted axially along the other pipe segments.

[0096] The sixth object of the present invention is to provide an oral drug delivery device, which includes the drug containing device described in the fourth object, and the oral drug delivery device also includes a tubular member, the tubular member has two openings and an inner cavity, one end opening is a first opening, and the other end opening is a second opening, and the inner cavity connects the first opening and the second opening; the drug containing device is arranged in the inner cavity and close to the first opening, and the space for carrying drug particles or multiple pills is connected to the second opening; the diameter of the first opening is smaller than the minimum diameter of the drug containing device.

[0097] In the present invention, by limiting the diameter of the first opening to be smaller than the minimum diameter of the drug containing device, the drug containing device can be maintained in the inner cavity in any manner and will not fall off from the first opening of the tubular member.

[0098] In the present invention, preferably, the diameter of the second opening is smaller than the minimum diameter of the drug containing device.

[0099] In the present invention, preferably, a top cover for sealing is also provided at the second opening to ensure that after the oral drug delivery device is loaded with drugs, even if it is bumped or completely inverted during transportation, the drug particles or pills will not leak from the second opening.

[0100] In the present invention, the specific description of the structure of the tubular member is the same as described in the fifth part of the object.

[0101] The seventh object of the present invention is to provide a drug containing device for solid oral preparations, which includes a filter component and a supporting component for supporting the filter component, the filter component and the supporting component cooperate with each other to form a space for carrying drug particles or multiple pills, the filter component has one or more channels allowing liquid to pass through; the channels are distributed in an up and down intricate and cross-shaped manner inside the filter component, and a water-soluble polymer material layer is also provided on the filter component, so that the drug particles or multiple pills cannot pass through.

[0102] The present solution has a wide range of applications, and is particularly suitable for situations where, in the particle size distribution of the drug particles or pellets, some particle sizes are smaller than or equal to the pore size of the pore channel.

[0103] The mechanism of this solution is that since the particle size distribution of drug particles or pills is a range, it is impossible to completely eliminate particles or pills smaller than a certain size due to process limitations. In this case, in order to ensure less resistance during sipping, a relatively large pore size will be selected when setting up an intricate and intersecting pore structure. In order to meet the requirement of no leakage, it is necessary to set a filter component (such as a filter membrane) as a intricate and intersecting pore structure and provide a water-soluble polymer material layer on the filter membrane.

[0104] The following is a detailed description of the structure, material, pore size, and preparation process of the filter element:

[0105] In the present invention, the filter element is a common type in the art, preferably a filter membrane. The filter membrane is preferably a cylindrical structure. The thickness of the filter membrane is preferably 0.3 to 20 mm, more preferably 0.5 to 15 mm, and further preferably 0.5 to 10 mm, for example 2 mm.

[0106] That is to say, the filter membrane has a certain thickness, so the pores of the filter membrane are arranged to have an intricate and intertwined structure up and down. Preferably, the upper and lower surfaces of the filter membrane and the internal pores are arranged to have an irregular and intricate and intertwined structure, such as a sponge-like porous structure, or a fluffy structure formed by irregularly stacking and pressing multiple layers of fibers.

[0107] The material of the filter membrane is a conventional filter membrane material in the art, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate, cellulose acetate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, glass fiber, nylon, polyether sulfone, polyvinylidene fluoride and polytetrafluoroethylene. The shape of the raw material of the filter membrane includes but is not limited to granular, sheet, fiber, etc.

[0108] The shape and structure of the pores in the filter membrane may be regular structures conventional in the art, such as connecting and penetrating the upper and lower surfaces of the filter membrane in a straight line.

[0109] The pore size of the filter membrane is conventional in the art, such as 1-500 μm, preferably 20-400 μm, more preferably 40-300 μm, such as 150 μm, 200 μm, 250 μm, 300 μm.

[0110] The diameter of the filter membrane can be conventional in the art. The diameter of the filter membrane is defined as the effective diameter for retaining solids and passing liquids. For design and installation process considerations, the outermost circle of the filter membrane diameter will be pressed in the middle by the upper and lower support members to fix the filter membrane. For example, a 10mm diameter membrane has 1mm of the edge pressed by the support member, and the effective diameter is only 8mm. The commonly used effective diameter range of the filter membrane is generally 4-20mm, preferably 6-15mm, more preferably 8mm-12mm, for example 10mm.

[0111] The preparation process of the filter membrane is a conventional process in the art, including but not limited to sintering, injection molding, pressing, weaving, etc.

[0112] The following is a detailed description of the configuration of the water-soluble polymer material layer:

[0113] In the present invention, the water-soluble polymer material layer is formed in a conventional manner in the art, preferably by adsorbing, coating or spraying a polymer material solution on the upper surface and / or lower surface of the filter membrane, or immersing the filter membrane in a polymer material solution, and then drying. After drying, the polymer material is dispersed in the membrane pores and membrane material of the filter membrane to form a skeleton with a certain hardness, while blocking the pores of the filter membrane, so that drug particles or pellets smaller than or equal to the pore size of the filter membrane will not leak during storage and transportation.

[0114] Specifically, the structures formed by the water-soluble polymer material layer are preferably the following two: a continuous water-soluble polymer material layer is formed on the upper surface or lower surface of the filter membrane, or the polymer material completely blocks the pores of the filter membrane to form a complete and dense water-soluble polymer material layer (for example, such a structure is formed by using an immersion method); more preferably, a continuous water-soluble polymer material layer is formed only on the upper surface or lower surface of the filter membrane (for example, such a structure is formed by adsorption, coating, or spraying only on a certain surface of the filter membrane); further preferably, a continuous water-soluble polymer material layer is formed on the lower surface of the filter membrane.

[0115] The dissolution time of the water-soluble polymer material layer is preferably less than or equal to 10 seconds, for example, 2 seconds. When in use, the patient places the drug containing device in the liquid and sips it. At the same time, the water-soluble polymer material layer dissolves in a very short time, and the liquid passes through the drug containing device with very little resistance, delivering the drug particles into the patient's mouth. Since the water-soluble polymer material layer dissolves very quickly, the patient cannot feel the change in resistance when using it.

[0116] In order to make the polymer material solution better formed on the surface of the filter membrane, it is preferred to select a polymer material solution with good water solubility and film-forming properties and a small molecular weight. The molecular weight of the polymer material is generally 2000-200000, preferably 2000-100000. More preferably, the type of the polymer material is selected from one or more of hydroxypropyl methylcellulose (HPMC), copovidone, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), povidone, polyethylene glycol (PEG), gelatin, poloxamer, xanthan gum and Eudragit.

[0117] The preparation method of the polymer material solution is a conventional method in the art, and specifically comprises the following steps: uniformly mixing the polymer material with a solvent, wherein the solvent is a conventional solvent in the art that can dissolve the polymer material and is volatile, such as water, ethanol, acetone, etc.

[0118] In the process of forming the water-soluble polymer material layer, the viscosity of the polymer material solution is a key parameter in the forming process. The viscosity depends on three parameters: the concentration, molecular weight and chemical structure of the polymer. The viscosity range is generally 2 centipoise (cP)-5000 centipoise (cP), preferably 2cP-1000cP. In the process of forming the water-soluble polymer material layer, the viscosity of the polymer material solution is a key parameter in the forming process. The viscosity range is generally 2 centipoise (cP)-5000 centipoise (cP), preferably 2cP-1000cP. In the process of forming the water-soluble polymer material layer, the viscosity of the polymer material solution is preferably 0.1%-30%, for example 10%, and the concentration is the mass percentage concentration. The weight gain of the polymer material is generally 0.01-60mg / cm 2 , preferably 0.5-30mg / cm 2, for example 6.4 mg / cm 2 .

[0119] In a preferred embodiment of the present application, the polymer material solution is a 10% concentration of hydroxypropyl methylcellulose E3 solution.

[0120] The structure of the supporting component is described in detail below:

[0121] In the present invention, the supporting component has a conventional meaning in the art, and its function is to support the filtering component without affecting the filtering property and liquid permeability of the filtering component.

[0122] In a preferred embodiment of the present application, the support component includes an upper support component and a lower support component, the upper support component and the lower support component can cover each other and clamp the filter component in the middle, and the space above the upper support component and the filter component is used to accommodate drug particles or multiple pills. This structure is similar to a sandwich form.

[0123] In another preferred embodiment of the present application, the support component includes a filter component accommodating component and a drug accommodating component, the filter component accommodating component and the drug accommodating component both have a porous structure end and an open end, the porous structure end has one or more holes that allow liquid to pass through, the open end of the filter component accommodating component and the porous structure end of the drug accommodating component can be covered to form a cavity for accommodating the filter component; the open end of the drug accommodating component is an open tubular structure for accommodating drug particles or pills. Those skilled in the art should understand that the actual function of the filter component accommodating component in this embodiment is to form a cavity with the drug accommodating component for accommodating the filter component, and this structure is also similar to a sandwich form. In addition, the size of the porous structure of the drug accommodating component and the filter component accommodating component does not affect the filterability and liquid permeability of the filter component.

[0124] Among them, the material of the supporting component is a conventional material in the field, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride, polytetrafluoroethylene, polyethylene terephthalate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, ceramics, silicon dioxide, and silicone.

[0125] The preparation process of the support component is conventional in the art, including but not limited to sintering, injection molding, etc.

[0126] The following is a detailed description of the forms and types of drug granules or pellets:

[0127] In the present invention, the drug granules or pellets have the conventional meaning in the art, and generally refer to granules, powders or pellets containing active drug ingredients.

[0128] The particle size of the drug particles or pellets is conventional in the art, generally 1-5000 μm, preferably 25-2000 μm, and more preferably 50-1000 μm.

[0129] Preferably, when the particle size of the drug particles or pellets is in the range of 50-1000 μm, the pore size of the filter component is in the range of 40-300 μm.

[0130] The active pharmaceutical ingredients contained in the drug particles or pellets are conventional in the art, including but not limited to one or more of the following: dabigatran etexilate or a pharmaceutically acceptable salt thereof, apixaban, rivaroxaban, levodopa-carbidopa, montelukast, lansoprazole, omeprazole, esomeprazole, amoxicillin, clarithromycin, azithromycin, metronidazole, rifampicin, sulfasalazine, acetaminophen, dextromethorphan, doxylamine, pseudoephedrine, diphenhydramine, amphetamine, methylphenidate, deferasirox, ivacaftor, lumacaftor, tacrolimus, diazepam, clobazam, vigabatrin, bosentan, melatonin, biotin, sodium disodium thiosulfate, amlodipine and esmolol.

[0131] The preparation process of the drug granules or pellets includes but is not limited to one or more of the following processes: wet granulation, dry granulation, extrusion spheronization, melt granulation, ion exchange resin granulation, and pellet spraying.

[0132] The eighth object of the present invention is to provide an oral drug delivery device, which includes the drug containing device described in the seventh object, and the oral drug delivery device also includes a tubular member, the tubular member has two openings and an inner cavity, one end opening is a first opening, and the other end opening is a second opening, and the inner cavity connects the first opening and the second opening; the drug containing device is externally connected to the free end of the first opening, and the space for carrying drug particles or multiple pills is connected to the inner cavity.

[0133] The following specifically describes the manner in which the drug containing device is externally disposed at the free end of the first opening:

[0134] In the present invention, the drug containing device is placed outside the tubular member, and is preferably maintained at the first opening outside the tubular member by a fixed sleeve manner or a threaded connection manner.

[0135] In this embodiment, particles or pills containing active pharmaceutical ingredients are placed in the cavity of the drug containing device. When in use, one end of the supporting component contacts the liquid, and the liquid is sucked into the tubular component through the filtering component by the suction action. The particles or pills containing active pharmaceutical ingredients enter the tubular component with the liquid and then enter the mouth.

[0136] In the present invention, preferably, a top cover for sealing is also provided at the second opening to ensure that after the oral drug delivery device is loaded with drugs, even if it is bumped or completely inverted during transportation, the drug particles or pills will not leak from the second opening.

[0137] The structure of the tubular member is described in detail below:

[0138] In a preferred embodiment of the present application, the tubular component is a straight straw. The straight straw preferably has at least one pleated structure. Preferably, the pleated structure has a pair of wings and a turning end; the pleated structure can be stretched or contracted along the axial direction of the tubular component and form turbulence when stretched.

[0139] In another preferred embodiment of the present application, the tubular component has at least two tube segments, which are sealed and connected to each other and can be stretched or contracted axially along the tubular component; when the tubular component is in a stretched state, a turbulence generating component having at least one step structure is formed.

[0140] Among them, when the number of the pipe segments is 3: the inner diameter of the first pipe segment in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe segment, the outer diameter of the second pipe segment is smaller than the inner diameter of the first pipe segment, and each pipe segment can be stretched or contracted axially along the other pipe segments; or, the inner diameter of the first pipe segment, the outer diameter of the second pipe segment, the inner diameter and the outer diameter of the third pipe segment in the direction from the first opening to the second opening gradually decrease, and each pipe segment can be stretched or contracted axially along the other pipe segments.

[0141] Among them, when the number of the pipe segments is 4: the inner diameter of the first pipe segment in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe segment, and the inner diameter of the second pipe segment is the same as the inner diameter of the fourth pipe segment, wherein the inner diameter of the second pipe segment is smaller than that of the first pipe segment, and each pipe segment can be stretched or contracted axially along the other pipe segments; or, the inner diameters of the first pipe segment to the fourth pipe segment in the direction from the first opening to the second opening gradually decrease, and each pipe segment can be stretched or contracted axially along the other pipe segments.

[0142] The ninth object of the present invention is to provide an oral drug delivery device, which includes the drug containing device described in the seventh object, and the oral drug delivery device also includes a tubular member, the tubular member has openings at both ends and an inner cavity, one end opening is a first opening, and the other end opening is a second opening, and the inner cavity connects the first opening and the second opening; the drug containing device is arranged in the inner cavity and close to the first opening, and the space used to carry drug particles or multiple pills is connected to the second opening; the diameter of the first opening is smaller than the minimum diameter of the drug containing device.

[0143] In the present invention, by limiting the diameter of the first opening to be smaller than the minimum diameter of the drug containing device, the drug containing device can be maintained in the inner cavity in any manner and will not fall off from the first opening of the tubular member.

[0144] In the present invention, preferably, the diameter of the second opening is smaller than the minimum diameter of the drug containing device.

[0145] In the present invention, preferably, a top cover for sealing is also provided at the second opening to ensure that after the oral drug delivery device is loaded with drugs, even if it is bumped or completely inverted during transportation, the drug particles or pills will not leak from the second opening.

[0146] In the present invention, the specific description of the structure of the tubular component is the same as described in Part 8 of the object.

[0147] Those skilled in the art should understand that, in the present invention, the descriptions of "first opening", "second opening", "first pipe section", "second pipe section", "third pipe section", "fourth pipe section", etc. are for the convenience of explanation and should not be understood as limitations on specific positions or orders.

[0148] On the basis of being in accordance with the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0149] The reagents and raw materials used in the present invention are commercially available.

[0150] The positive and progressive effects of the present invention are: the drug containing device of the present invention can better solve the problems of drug particle leakage and large fluid resistance during sipping, and the oral drug delivery device formed after being combined with the tubular component can be used as a drug packaging material that directly contacts the drug and has a storage function. When the oral drug delivery device of the present invention is in use, it has been tested that when the length of the straw is 20 cm, the time for the liquid filling the straw to be emptied under the action of gravity alone is less than 12 seconds. BRIEF DESCRIPTION OF THE DRAWINGS

[0151] Figure 1 1 is a schematic diagram of the structure of the support component and the filter component in the drug containing device of Example 1, 1a is the lower support component, 1b is the filter component, and 1c is the upper support component;

[0152] Figure 2 2a is a schematic diagram of the assembly of the support component and the filter component in the drug containing device of Example 1, 2a is before the assembly, and 2b is after the assembly;

[0153] Figure 3 is a schematic structural diagram of a built-in oral drug delivery device formed by assembling the drug containing device of Example 1 with a straw;

[0154] Figure 4 4a is a structural schematic diagram of a support component and a filter component of a drug containing device of Example 2, 4b is a cage-shaped support component, 4c is an upper cover of the cage-shaped support component;

[0155] Figure 5 is a schematic diagram of the assembly of the support component and the filter component of the drug containing device of Example 2;

[0156] Figure 6 is a schematic diagram of a built-in oral drug delivery device formed by assembling the drug containing device of Example 2 with a straw;

[0157] Figure 7 7a is a schematic diagram of the built-in oral drug delivery device of Examples 1 to 3 when used with a straw, 7b is before sipping, and 7a is after sipping;

[0158] Figure 8 8a is a schematic structural diagram of a filter component accommodating component, a filter component and a drug accommodating component in a drug accommodating device of Example 4, 8b is a filter component, and 8c is a drug accommodating component;

[0159] Fig. 9 9a is a schematic diagram of the assembly of the filter component, the filter component and the drug containing component in the drug containing device of Example 4, 9a is before the assembly, and 9b is after the assembly;

[0160] Fig.10 is a schematic diagram of an external oral drug delivery device formed after the drug containing device of Example 4 is assembled with a straw;

[0161] Fig.11 11a is a schematic diagram of the external oral drug delivery device of Example 4 when used with a straw, 11a is before sipping, and 11b is after sipping;

[0162] Fig.12 A cross-sectional view of the filter component in the embodiment in which the internal channels are irregular and intricately crossed;

[0163] Fig.13 is a schematic structural diagram of a drug containing device according to Example 8;

[0164] Fig.14 Schematic diagram of the structure of the oral drug delivery device of Example 8. DETAILED DESCRIPTION

[0165] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0166] Example 1 (water-soluble polymer material layer + built-in)

[0167] like Figures 1 to 3 As shown, a filter membrane with a pore size of 150 μm, a thickness of 0.2 mm, and a material of polypropylene was cut into a disc with a diameter of 1 cm. The above filter membrane was soaked in a 10% hydroxypropyl methylcellulose E3 solution and then dried in an oven. After drying (weight gain of 6.4 mg / cm 2 ), and place it between two polyethylene discs with a diameter of 1 cm and a thickness of 3 mm. The two polyethylene discs are covered with 2 mm×2 mm grids that are transparent from top to bottom. One of the polyethylene discs has four protrusions with a diameter of 2 mm on the surface, and the other polyethylene disc has four pits with a diameter of 2 mm at symmetrical positions on the surface. The two discs are mechanically condensed with the concave and convex structures to tightly fix the filter membrane in the middle to form a drug containing device. The device is placed from the nozzle at the end that contacts the liquid into a wrinkled straw with an inner diameter of 1.05 cm, and the nozzle is bent inward, so that the drug containing device can be retained in the straw.

[0168] Embodiment 2 (intricate cross-channel structure + built-in)

[0169] like Figures 4 to 6 As shown, a filter membrane with a pore size of 300 μm, a thickness of 6 mm, and a material of polypropylene (the filter membrane is provided with intricate and cross-shaped irregular channels) ( Fig.12 yes Figure 4 and Figure 8 Schematic diagram of the internal channel structure of the filter component in the middle), cut into a cylinder with a diameter of 8mm. The above cylindrical filter membrane is placed in a cylindrical filter membrane containing device with an inner cavity diameter of 8.1mm and a height of 6mm; the bottom and cover of the cylinder are covered with 2mm×2mm vertically transparent grids; the cylinder cover is fixed to the cylinder body by mechanical condensation, and the filter membrane is wrapped therein to form a drug containing device. The device is placed from the end of the tube that contacts the liquid into a wrinkled straw with an inner diameter of 1.2cm, and the tube mouth is bent inward, so that the drug containing device can be retained in the straw.

[0170] Example 3 (intricate cross-channel structure + water-soluble polymer material layer + built-in)

[0171] like Figures 1 to 3 As shown, a polypropylene filter membrane with a pore size of 300 μm, a thickness of 1.5 mm, and a material of 1 cm diameter was cut into discs. The above filter membrane was soaked in a 10% hydroxypropyl methylcellulose E3 solution and then dried in an oven. After drying (weight gain of 25.5 mg / cm 2), and place it between two polyethylene discs with a diameter of 1 cm and a thickness of 3 mm. The two polyethylene discs are covered with 2 mm×2 mm grids that are transparent from top to bottom. One of the polyethylene discs has four protrusions with a diameter of 2 mm on the surface, and the other polyethylene disc has four pits with a diameter of 2 mm at symmetrical positions on the surface. The two discs are mechanically condensed with the concave and convex structures to tightly fix the filter membrane in the middle to form a drug containing device. The device is placed from the nozzle at the end that contacts the liquid into a wrinkled straw with an inner diameter of 1.05 cm, and the nozzle is bent inward, so that the drug containing device can be retained in the straw.

[0172] The schematic diagram of the structure of the device of Embodiments 1, 2 and 3 when in use is as shown in Figure 7 shown.

[0173] Embodiment 4 (intricate cross-channel structure + external)

[0174] like Figures 8 to 11 As shown, a filter membrane with a pore size of 100 μm, a thickness of 2 mm, and a material of polypropylene (the filter membrane is provided with intricate and cross-shaped irregular channels) is cut into a disc with a diameter of 12 mm. The accommodating component of the filter component and the drug accommodating component are prepared by injection molding. The above-mentioned filter component accommodating component is a cylindrical structure with an inner diameter of 12.1 mm and an inner height of 4 mm, and the bottom of the cylinder has a circular hole with a diameter of 8 mm that is transparent from top to bottom; the above-mentioned drug accommodating component is a cylindrical structure with an inner diameter of 9.1 mm and an inner height of 1.5 cm. The filter membrane is placed in the cylindrical structure of the filter component accommodating component, and then the lower end of the drug accommodating component is pressed on it. The two are condensed by a mechanical structure to fix the filter membrane in the middle to obtain a drug accommodating device. Then the upper end of the drug accommodating device is connected to the nozzle of the liquid contact end with a pleated straw (inner diameter 8.6 mm). The dabigatran mesylate granules (containing 75mg dabigatran etcxilate, particle size distribution is shown in Table 1) of 504.1mg hot-melt granulation are filled into the above-mentioned medicine accommodating device by the upper end of straw, and no granules are leaked by the medicine accommodating device. During use, one end of straw with medicine accommodating device is placed in liquid, and the patient sucks liquid in the straw by sipping, and liquid easily passes through the medicine accommodating device and promotes the dabigatran mesylate granules to enter the patient's mouth, completes medication.

[0175] Table 1 Particle size distribution of dabigatran etexilate mesylate particles by hot melt granulation

[0176] Particle size range percentage >355μm 23.8％ 250-355μm 7.6％ 180-250μm 35.9％ 180μm 32.7％

[0177] Example 5 (intricate cross-channel structure + water-soluble polymer material layer + external)

[0178] like Figures 8 to 11As shown, a filter membrane with a pore size of 300 μm, a thickness of 1.5 mm, and a material of polypropylene, with intricate and irregular pores, was cut into a disc with a diameter of 12 mm. The above filter membrane was soaked in 10% Killidon VA64 (copolyvidone) ethanol solution, and then dried in an oven. The weight gain after drying was 16.0 mg / cm 2 . The filter component receiving component and the drug receiving component were prepared by injection molding. The filter component receiving component is a cylindrical structure with an inner diameter of 12.1 mm and an inner height of 4 mm, and the bottom of the cylinder has a round hole with a diameter of 8 mm that is transparent from top to bottom; the drug receiving component is a cylindrical structure with an inner diameter of 9.1 mm and an inner height of 1.5 cm. The filter membrane is placed in the cylindrical structure of the filter component receiving component, and then the lower end of the drug receiving component is pressed on it. The two are condensed by a mechanical structure to fix the filter membrane in the middle to obtain a drug receiving device. Then the upper end of the drug receiving device is connected to the nozzle of the liquid contact end with a pleated straw (inner diameter 8.6 mm). 500 mg of D-mannitol pellets with a particle size range of 75 μm-150 μm are filled into the cylinder of the above-mentioned drug receiving device through the upper end of the straw, and no small pills leak through the drug receiving device.

[0179] Example 6 (water-soluble polymer material layer + external placement)

[0180] like Figures 8 to 11 As shown, a filter membrane with a pore size of 250 μm, a thickness of 0.3 mm, and a material of polypropylene was cut into a disc with a diameter of 12 mm. The above filter membrane was soaked in 10% Killidon VA64 (copolyvidone) ethanol solution and then dried in an oven. The weight gain after drying was 8.9 mg / cm 2 . The filter component accommodating component and the drug accommodating component are prepared by injection molding. The filter component accommodating component is a cylindrical structure with an inner diameter of 12.1mm and an inner height of 3mm. The bottom of the cylinder has a round hole with a diameter of 8mm that is transparent from top to bottom; the drug accommodating component is a cylindrical structure with an inner diameter of 9.1mm and an inner height of 1.5cm. The filter membrane is placed in the cylindrical structure of the filter component accommodating component, and then the lower end of the drug accommodating component is pressed on it. The two are condensed by a mechanical structure to fix the filter membrane in the middle to obtain a drug accommodating device. The upper end of the drug accommodating device is then connected to the nozzle of the liquid-contacting end with a pleated straw (inner diameter 8.6mm).

[0181] Example 7 (intricate cross-channel structure + external)

[0182] The drug containing device in Example 4 was assembled with a straw having a total length of 20 cm, an inner diameter of 8.6 mm, and a fold length of 4 cm. The lower end of the drug containing device was blocked with a finger, and the straw was filled with liquid from the upper end. Under the action of gravity, the liquid in the device was emptied in about 2 to 3 seconds.

[0183] Example 8 (water-soluble polymer material layer + external placement)

[0184] like Figures 13-14 As shown, the drug containing device is prepared by injection molding process. The above drug containing device is a cylindrical structure with an inner diameter of 9mm, a height of 2cm, and a wall thickness of 1mm; the inner diameter of the bottom of the cylinder is 9mm, and there are multiple screens with a pore size of 200μm; the inner wall of the cylinder mouth is designed with two circles of raised ring structures for connecting the straw in an external way. 7.5% HPMC E3 aqueous solution is applied to the inner surface of the bottom of the cylinder and dried, and the weight gain is 17.7mg / cm 2 , and obtain a drug containing device.

[0185] Embodiment 9 (intricate cross-channel structure + external)

[0186] like Figures 8 to 11 As shown, a filter membrane with a pore size of 100 μm, a thickness of 2 mm, and a material of polypropylene (the filter membrane is provided with intricate and cross-shaped irregular channels) is cut into a disc with a diameter of 16 mm. The filter component receiving component and the drug receiving component are prepared by injection molding. The filter component receiving component is a cylindrical structure with an inner diameter of 16.1 mm and an inner height of 4 mm, and the bottom of the cylinder has a round hole with a diameter of 12 mm that is transparent from top to bottom; the drug receiving component is a cylindrical structure with an inner diameter of 12.5 mm and an inner height of 1.5 cm. The filter membrane is placed in the cylindrical structure of the filter component receiving component, and then the lower end of the drug receiving component is pressed on it. The two are condensed by a mechanical structure to fix the filter membrane in the middle to obtain a drug receiving device. Then the upper end of the drug receiving device is connected to the nozzle of the liquid contact end with a pleated straw (inner diameter 12 mm). 320mg omeprazole enteric-coated multi-pills (containing 20mg omeprazole), 1334mg amoxicillin granules (containing 1000mg amoxicillin) and 840mg clarithromycin granules (containing 500mg clarithromycin) were filled into the drug containing device through the upper end of the straw, and no multi-pills or granules leaked through the drug containing device. During use, the end of the straw with the drug containing device was placed in the liquid, and the patient sucked the liquid into the straw by sipping, and the liquid easily passed through the drug containing device and pushed the multi-pills into the patient's mouth to complete the medication. The particle size range of the omeprazole enteric-coated multi-pills is 0.25-0.355mm. The particle size distribution of the amoxicillin granules and the clarithromycin granules is shown in Tables 2 and 3.

[0187] Table 2 Amoxicillin particle size distribution

[0188] Particle size range percentage 425-600μm 22.8％ 250-425μm 33.6％ 150-250μm 25.7％ <150μm 17.9％

[0189] Table 3 Clarithromycin particle size distribution

[0190] Particle size range percentage 425-600μm 32.1％ 250-425μm 16.7％ 150-250μm 28.9％ <150μm 22.3％

Claims

1. A drug containing device for solid oral preparations, It is characterized in that It includes a filter component and a support component for supporting the filter component. The filter component and the support component cooperate with each other to form a space for carrying drug particles or multiple pills. The filter component has one or more channels that allow liquid to pass through; the channels are distributed in an up and down intricate and cross-shaped manner inside the filter component, so that the channels extend up and down through the filter component. A water-soluble polymer material layer is also provided on the filter component, so that the drug particles or multiple pills cannot pass through. The thickness of the filter component is more than 0.5 mm.

2. The drug containing device according to claim 1, It is characterized in that The filtering component is a filter membrane.

3. The drug containing device according to claim 1, It is characterized in that The particle size of the drug particles or pellets is 1-5000 μm.

4. The drug containing device according to claim 1, It is characterized in that The active pharmaceutical ingredients contained in the pharmaceutical granules or pellets include, but are not limited to, one or more of the following: dabigatran etexilate or a pharmaceutically acceptable salt thereof, apixaban, rivaroxaban, levodopa-carbidopa, montelukast, lansoprazole, omeprazole, esomeprazole, amoxicillin, clarithromycin, azithromycin, metronidazole, rifampicin, sulfasalazine, acetaminophen, dextromethorphan, doxylamine, pseudoephedrine, diphenhydramine, amphetamine, methylphenidate, deferasirox, ivacaftor, lumacaftor, tacrolimus, diazepam, clobazam, vigabatrin, bosentan, melatonin, biotin, sodium disodium thiothreitol, amlodipine and esmolol.

5. The drug containing device according to claim 2, It is characterized in that The filter membrane is in the shape of a cylindrical structure.

6. The drug containing device according to claim 2, It is characterized in that The thickness of the filter membrane is 0.5-20 mm.

7. The drug containing device according to claim 2, It is characterized in that The upper and lower surfaces of the filter membrane and the internal pores are arranged in an irregular and intricately intersecting structure.

8. The drug containing device according to claim 2, It is characterized in that The pore size of the filter membrane is 1-500 μm.

9. The drug containing device according to claim 2, It is characterized in that The effective diameter of the filter membrane is 4-20 mm.

10. The drug containing device according to claim 6, It is characterized in that The thickness of the filter membrane is 0.5-15 mm.

11. The drug containing device according to claim 10, It is characterized in that The thickness of the filter membrane is 0.5-10 mm.

12. The drug containing device according to claim 7, It is characterized in that The irregular and intricately intersecting structure is a sponge-like porous structure.

13. The drug containing device according to claim 7, It is characterized in that The irregular and intricately interlaced structure is a fluffy structure formed by pressing multiple layers of fibers in an irregularly stacked arrangement.

14. The drug containing device according to claim 8, It is characterized in that The pore size of the filter membrane is 20-400 μm.

15. The drug containing device according to claim 14, It is characterized in that The pore size of the filter membrane is 40-300 μm.

16. The drug containing device according to claim 9, It is characterized in that The effective diameter of the filter membrane is 6-15 mm.

17. The drug containing device according to claim 16, It is characterized in that The effective diameter of the filter membrane is 8mm-12mm.

18. The drug containing device according to claim 3, It is characterized in that The particle size of the drug particles or pellets is 25-2000 μm.

19. The drug containing device according to claim 18, It is characterized in that The particle size of the drug granules or pellets is 50-1000 μm.

20. The drug containing device according to claim 19, It is characterized in that When the particle size of the drug particles or pellets is in the range of 50 to 1000 μm, the pore size of the filter component is in the range of 40 to 300 μm.

21. The drug containing device according to any one of claims 2 and 5-17, It is characterized in that The water-soluble polymer material layer has two structures as follows: forming a continuous water-soluble polymer material layer on the upper surface or lower surface of the filter membrane, or completely blocking the pores of the filter membrane and forming a complete and dense water-soluble polymer material layer.

22. The drug containing device according to any one of claims 2 to 20, It is characterized in that The dissolution time of the water-soluble polymer material layer is less than or equal to 10 seconds.

23. The drug containing device according to any one of claims 2 to 20, It is characterized in that The molecular weight of the polymer material in the water-soluble polymer material layer is 2000-200000.

24. The drug containing device according to any one of claims 2 to 20, It is characterized in that The type of the polymer material in the water-soluble polymer material layer is selected from one or more of hydroxypropyl methylcellulose, copovidone, hydroxypropyl cellulose, hydroxyethyl cellulose, povidone, polyethylene glycol, gelatin, poloxamer, xanthan gum and Eudragit.

25. The drug containing device according to any one of claims 2 to 20, It is characterized in that During the forming process of the water-soluble polymer material layer, the polymer material weight gain is 0.01-60 mg / cm 2 .

26. The drug containing device according to claim 23, It is characterized in that The molecular weight of the polymer material in the water-soluble polymer material layer is 2000-100000.

27. The drug containing device according to claim 25, It is characterized in that The polymer material weight gain is 0.5-30 mg / cm 2 .

28. The drug containing device according to claim 1, It is characterized in that The structure of the supporting component is any one of the following structures: The support component comprises an upper support component and a lower support component, the upper support component and the lower support component cover each other and clamp the filter component in the middle, and the space above the upper support component and the filter component is used to accommodate drug particles or multiple pills; Alternatively, the supporting component includes a filter component accommodating component and a drug accommodating component, the filter component accommodating component and the drug accommodating component both having a porous structure end and an open end, the porous structure end having one or more holes allowing liquid to pass through, the open end of the filter component accommodating component and the porous structure end of the drug accommodating component are covered to form a cavity for accommodating the filter component; the open end of the drug accommodating component is an open tubular structure for accommodating drug particles or pills.

29. An oral drug delivery device, It is characterized in that It includes the drug containing device as described in any one of claims 1 to 28, and the oral drug delivery device also includes a tubular member, the tubular member has openings at both ends and an inner cavity, one end opening is a first opening, and the other end opening is a second opening, and the inner cavity connects the first opening and the second opening; the drug containing device is externally connected to the free end of the first opening, and the space for carrying drug particles or multiple pills is connected to the inner cavity.

30. The oral drug delivery device of claim 29, It is characterized in that The drug containing device is placed outside the tubular component and is maintained at the first opening of the tubular component by a fixed sleeve manner or a threaded connection manner.

31. The oral drug delivery device of claim 29, It is characterized in that The second opening is also provided with a top cover for sealing.

32. The oral administration delivery device of claim 29, It is characterized in that The tubular component is a straight straw.

33. The oral drug delivery device of claim 29, It is characterized in that The tubular member has at least two tube sections, the tube sections are sealed and connected to each other and stretched or contracted along the axial direction of the tubular member; when the tubular member is in a stretched state, a turbulence generating component having at least one step structure is formed; Wherein, when the number of the pipe segments is 3: the inner diameter of the first pipe segment in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe segment, the outer diameter of the second pipe segment is smaller than the inner diameter of the first pipe segment, and each pipe segment stretches or contracts axially along the other pipe segments; or, the inner diameter of the first pipe segment, the outer diameter of the second pipe segment, the inner diameter of the second pipe segment, and the outer diameter of the third pipe segment in the direction from the first opening to the second opening gradually decrease, and each pipe segment stretches or contracts axially along the other pipe segments; Among them, when the number of the pipe segments is 4: the inner diameter of the first pipe segment in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe segment, and the inner diameter of the second pipe segment is the same as the inner diameter of the fourth pipe segment, wherein the inner diameter of the second pipe segment is smaller than that of the first pipe segment, and each pipe segment is axially stretched or contracted along the other pipe segments; or, the inner diameters of the first pipe segment to the fourth pipe segment in the direction from the first opening to the second opening gradually decrease, and each pipe segment is axially stretched or contracted along the other pipe segments.

34. The oral drug delivery device of claim 32, It is characterized in that The straight straw has at least one pleated structure.

35. The oral drug delivery device of claim 34, It is characterized in that The pleated structure has a pair of wings and a turning end. The pleated structure stretches or contracts along the axial direction of the tubular member and forms turbulence when stretched.

36. An oral drug delivery device, It is characterized in that It includes a drug containing device as described in any one of claims 1 to 28, and the oral drug delivery device also includes a tubular member, the tubular member has openings at both ends and an inner cavity, one end opening is a first opening, and the other end opening is a second opening, and the inner cavity connects the first opening and the second opening; the drug containing device is arranged in the inner cavity and close to the first opening, and the space for carrying drug particles or multiple pills is connected to the second opening; the diameter of the first opening is smaller than the minimum diameter of the drug containing device.

37. The oral drug delivery device of claim 36, It is characterized in that The diameter of the second opening is smaller than the minimum diameter of the drug containing device.

38. The oral drug delivery device of claim 36, It is characterized in that The second opening is also provided with a top cover for sealing.

39. The oral drug delivery device of claim 36, It is characterized in that The structure of the tubular member is as described in any one of claims 32-35.

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