WO2021062987A1 - 固体口服制剂的药物容置装置及含其的口服给药递送装置 - Google Patents

固体口服制剂的药物容置装置及含其的口服给药递送装置 Download PDF

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Publication number
WO2021062987A1
WO2021062987A1 PCT/CN2020/079017 CN2020079017W WO2021062987A1 WO 2021062987 A1 WO2021062987 A1 WO 2021062987A1 CN 2020079017 W CN2020079017 W CN 2020079017W WO 2021062987 A1 WO2021062987 A1 WO 2021062987A1
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WIPO (PCT)
Prior art keywords
opening
pipe section
filter
drug
accommodating
Prior art date
Application number
PCT/CN2020/079017
Other languages
English (en)
French (fr)
Inventor
董良昶
雷杨
吴刚
张世忠
石劲敏
陈溪山
Original Assignee
上海汉都医药科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Priority claimed from CN201910939687.8A external-priority patent/CN110559185A/zh
Priority claimed from CN201921652286.6U external-priority patent/CN211634348U/zh
Application filed by 上海汉都医药科技有限公司 filed Critical 上海汉都医药科技有限公司
Priority to EP20870819.8A priority Critical patent/EP4042999A4/en
Priority to JP2022516463A priority patent/JP7457411B2/ja
Priority to US17/625,260 priority patent/US20220257471A1/en
Publication of WO2021062987A1 publication Critical patent/WO2021062987A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J7/00—Devices for administering medicines orally, e.g. spoons; Pill counting devices; Arrangements for time indication or reminder for taking medicine
    • A61J7/0015—Devices specially adapted for taking medicines
    • A61J7/0038—Straws

Definitions

  • the invention relates to the field of medical devices, and in particular to a medicine containing device for a solid oral preparation and an oral drug delivery device containing the same.
  • Tablets and capsules are the most convenient and accepted oral dosage forms. However, some patients, especially children and the elderly, often have difficulty swallowing large-sized tablets and capsules; some patients are reluctant to take this drug due to unacceptable taste. Therefore, the prior art proposes various drug delivery devices, which can promote the swallowing of large-size tablets and capsules, and minimize the patient's perception of the dose and taste of the drug.
  • Various drug delivery devices involve a drug containing member capable of containing and storing drugs. The following patents and applications related to the drug containing member of a sipping device are incorporated herein by reference.
  • EP0383503 A1 describes an improved device.
  • the drug containing part of the device is a screen.
  • the surface area of the screen is larger than the cross-sectional area of the inner cavity of the tube. It is used to hold and position a unit dose of therapeutic agent in the tube.
  • the device is adapted to deliver the dose through the tube with a fluid stream through the patient's normal sipping action.
  • U.S. Patent No. 6,096,003 describes a sipping device.
  • the drug containing component of the device is a stopper.
  • the stopper can be used to contain the active drug ingredient, and the liquid drives the stopper to slide upward in the lumen to complete the delivery of the drug.
  • US Patent No. 6109538 discloses a sipping device.
  • the accommodating part of the device is a pair of screens with rectangular grids, which are arranged in the lumen and used to limit the seasoning objects.
  • U.S. Patent No. 6,330,050 B2 describes a sipping device.
  • the drug containing part of the device is a one-way valve, which is used to accommodate drugs when it is not a sippy body, and deforms when sipped, allowing liquid to pass through.
  • U.S. Patent No. 8334003 B2 describes a sipping device, which includes an elongated tubular member with a pair of filter devices at each end of the tubular member to keep the flavor particles in the filter device, so that the flavoring agent can enter through normal suction In ordinary drinks.
  • US Patent No. 6,224,908 B1 describes an active pharmaceutical ingredient delivery device with a fluid controller.
  • the fluid controller is a porous plug, which has low friction with the tube wall and accommodates the medicine in a non-sucking state. When sipping, it is pushed by the fluid to accelerate the delivery of the medicine into the patient's mouth.
  • API-containing particles or pellets prepared by wet granulation, dry granulation, extrusion spheronization, melt granulation and other processes generally have a relatively wide particle size distribution, including particles that are much larger than the average particle size. Or multi-pills, there are also fine powder particles and multi-pills that are much smaller than the average particle size.
  • the liquid can pass through the medicament accommodating part smoothly with low resistance, so that the patient does not take effort when sipping; at the same time, the aperture of the medicament accommodating part is required to be smaller than the diameter of all particles or multiple pills , To ensure that the particles or multi-pill will not leak through the medicine containing part.
  • the pore size is large enough so that the resistance to liquid passage is small; but the larger the pore size, the greater the probability of leakage of particles and multiple pellets with smaller diameter. This limits the scope of application, and materials containing particles or multiple 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 sieved, which reduces the yield and increases the cost.
  • the technical problem to be solved by the present invention is to overcome the defects of the leakage of drug particles or multiple pills in the device for promoting drug swallowing in the prior art and the large fluid resistance during sipping, and to provide a drug containing device for solid oral preparations And an oral drug delivery device containing the same.
  • the drug accommodating device of the present invention is integrated with the straw when used, and is used for accommodating particles or multiple pills containing active drug ingredients with a particle size greater than, equal to or smaller than the aperture of the drug accommodating device.
  • the inventor 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 achieve a balance. Therefore, the technical difficulty of the present invention lies in finding a reasonable solution. It is necessary to ensure that the liquid resistance is small, but also to ensure that the loaded particles and multi-pill do not leak.
  • the present invention allows two mechanisms for accommodating drug particles or multiple pellets with a particle size less than or equal to the pore size of the filter element: one is to trap fine particles in the filter element through irregularly staggered pores in the filter element
  • This kind of filter component requires a certain thickness, such as a thickness of 0.5mm or more; the other is to form a membrane on the filter component through a water-soluble polymer material to block the holes of the filter component.
  • the polymer material dissolves instantaneously, and the water flows through it to drive the medicine into the patient's mouth. This mechanism does not require the thickness of the filter component.
  • One of the objectives of the present invention is to provide a medicine containing device for a solid oral preparation, which comprises a filter member and a support member for supporting the filter member, and the filter member and the support member cooperate with each other to form A space that carries drug particles or multiple pellets, the filter element has one or more pores that allow liquid to pass through; when the thickness of the filter element is 0.5 mm or more, the pores intersect up and down in the interior of the filter element It is distributed in such a way that the drug particles or pills cannot pass through.
  • the filter component is a common type in the field, preferably a filter membrane.
  • the shape of the filter membrane is preferably a cylindrical structure.
  • the thickness of the filter membrane is preferably 0.5-20 mm, more preferably 0.5-15 mm, still more preferably 0.5-10 mm, for example 2 mm.
  • the filter membrane has a certain thickness, so the pores of the filter membrane are arranged in an intricately intersecting structure, preferably the upper and lower surfaces of the filter membrane and the inner pores are arranged in an irregular and intricate structure, For example, a sponge-like porous structure, or a fluffy structure formed by multiple layers of fibers randomly stacked and pressed.
  • the pores of the filter membrane are arranged in an intricately intersecting structure, preferably the upper and lower surfaces of the filter membrane and the inner pores are arranged in an irregular and intricate structure, For example, a sponge-like porous structure, or a fluffy structure formed by multiple layers of fibers randomly stacked and pressed.
  • the particle size of the drug particles or pellets is less than or equal to the pore size of the filter membrane, they will not directly pass through the drug containing device as through a screen. Due to the tortuous and intricate intersection of the membrane pores, small drug particles or pellets will accumulate on the surface and inside. When the liquid passes, the drug particles or pellets accumulated on the surface and inside of the filter membrane are delivered into
  • the material of the filter membrane is a conventional filter membrane material in the field, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyvinyl chloride Ethylene phthalate, cellulose acetate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, glass fiber, nylon, polyethersulfone, polyvinylidene fluoride and polytetrafluoroethylene.
  • the shape of the raw material of the filter membrane is conventional in the art, including but not limited to granular, flake, fibrous, etc.
  • the pore size of the filter membrane is conventional in the art, such as 1-500 ⁇ m, preferably 20-400 ⁇ m, more preferably 40-300 ⁇ m, such as 150 ⁇ m, 200 ⁇ m, 250 ⁇ m, 300 ⁇ m.
  • the diameter of the filter membrane can be conventional in the field, and the diameter of the filter membrane is defined as the effective diameter that can retain solids and pass liquid.
  • the diameter of the filter membrane is defined as the effective diameter that can retain solids and pass liquid.
  • the upper and lower support parts of the fixed filter membrane are pressed in the middle, for example, a membrane with a diameter of 10mm, 1mm on the side is pressed by the support part, 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.
  • the preparation process of the filter membrane is a conventional process in the field, including but not limited to sintering, injection molding, pressing, weaving, etc.
  • the support member has a conventional meaning in the art, and its function is to support the filter member without affecting the filterability and liquid permeability of the filter member.
  • the structure is preferably: set on the upper and lower surfaces of the filter component, clamp the filter component in the middle, that is, sandwich the filter component in the middle like a sandwich; or clamp the filter component in a cage-like structure Wrapped inside.
  • the supporting member includes an upper supporting member and a lower supporting member, and the upper supporting member and the lower supporting member can cover each other and clamp the filter member in the middle.
  • the space above the upper support member and the filter member is used for accommodating drug particles or multiple pills. This structure is similar to a sandwich form.
  • the support member includes a filter member accommodating member and a medicine accommodating member, and both the filter member accommodating member and the medicine accommodating member have a hole-like structure end. And an open end, the pore-like structure end has one or more holes that allow liquid to pass through, and the open end of the filter component accommodating component and the pore 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 multiple pills.
  • 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.
  • the size of the pore-like structure of the medicine containing part and the filtering part containing part does not affect the filterability and liquid permeability of the filtering part.
  • the support member includes a cage-shaped support member with an upward opening and an upper cover that cooperates with the cage-shaped support member, and the upper cover is provided with drug particles or more. Pills and channels through which the liquid flows, the cage-shaped support member and the upper cover can enclose a hollow space and confine the filter member in the space. The upper cover and the upper space of the filter member can be enclosed to form a hollow space. Used to hold drug particles or multiple pills. This structure is similar to the form of a cage structure.
  • the material of the supporting member 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, poly Tetrafluoroethylene, polyethylene terephthalate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, ceramics, silicon dioxide, silicone.
  • the preparation process of the supporting member is conventional in the art, including but not limited to sintering, injection molding and the like.
  • the drug particles or pellets have conventional meanings in the art, and generally refer to particles, powders or pellets containing active pharmaceutical ingredients.
  • the particle size of the drug particles or pellets is conventional in the art, and is generally 1-5000 ⁇ m, preferably 25-2000 ⁇ m, and more preferably 50-1000 ⁇ m.
  • the pore size of the filter component is 40-300 ⁇ m.
  • the active pharmaceutical ingredients contained in the pharmaceutical particles or pills are conventional in the art, including but not limited to one or more of the following: dabigatran etexilate or a pharmaceutically acceptable salt thereof (for example, dabigatran etexilate) Bigatran etexilate), apixaban, rivaroxaban, levodopa-carbidopa, montelukast, lansoprazole, omeprazole, esomeprazole, amoxicillin, Clarithromycin, Azithromycin, Metronidazole, Rifampicin, Sulfasalazine, Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine, Diphenhydramine, Amphetamine, Methylphenidate, Delarose , Ivacaftor, lumacaftor, tacrolimus, diazepam, clobazam, vigabatri
  • the preparation process of the drug particles or multiple 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, pellet spraying Apply medicine.
  • 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 further includes a tubular member with openings at both ends And an inner cavity, one end of which is a first opening, and the other end is a second opening, the inner cavity is connected to the first opening and the second opening; the medicine containing device circumscribes the free space of the first opening And the space used to carry the drug particles or multiple pills is connected to the inner cavity.
  • the drug accommodating device is placed outside the tubular member and maintained at the first opening of the tubular member through a fixed sleeve method or a threaded connection method.
  • particles or pellets containing active pharmaceutical ingredients are placed in the cavity of the drug containing device.
  • one end of the supporting member contacts the liquid, and the liquid is sucked into the tubular member through the filter member by sipping, and contains the active
  • the granules or pellets of the drug component enter the tubular member with the liquid, and then enter the mouth.
  • the second opening is also provided with a top cover for sealing to ensure that after the oral drug delivery device is loaded with drugs, even if bumps or completely inverted during transportation, there will be more drug particles. The pill will not leak from the second opening.
  • the oral drug delivery device loaded with medicine can also be stored or transported directly after being sealed by a separate outer package, which plays a role of waterproof and moisture-proof.
  • the tubular member is a straight straw.
  • the straight straw has at least one fold structure.
  • the corrugated portion structure has a pair of wings and a turning end; the corrugated portion structure can be stretched or contracted along the axial direction of the tubular member, and forms turbulence during stretching.
  • the tubular component has at least two pipe sections, and the pipe sections are connected in a sealed manner and can be stretched or contracted along the axial direction of the tubular member; the tubular member is in a stretched state At this time, a turbulence generating part having at least one step structure is formed.
  • the inner diameter of the first pipe section in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe section, and the outer diameter of the second pipe section is smaller than that of the third pipe section.
  • the inner diameter of the first pipe section, and each pipe section can be stretched or contracted along the axial direction of other pipe sections; or, the inner diameter of the first pipe section and the second pipe section in the direction from the first opening to the second opening
  • the outer diameter, inner diameter, and outer diameter of the third pipe section gradually decrease, and each pipe section can be stretched or contracted along the axis of other pipe sections.
  • the inner diameter of the first pipe section in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe section
  • the inner diameter of the second pipe section is the same as that of the fourth pipe section.
  • the inner diameters of the pipe sections are the same, wherein the inner diameter of the second pipe section is smaller than the first pipe section, and each pipe section can be stretched or contracted in the axial direction of other pipe sections; or, it extends from the first opening to the second pipe section.
  • the inner diameters of the first pipe section to the fourth pipe section in the opening direction gradually decrease, and each pipe section can be stretched or contracted along the axial direction of the other pipe sections.
  • 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 further includes a tubular member with openings at both ends And an inner cavity, one end of which is a first opening, and the other end is a second opening, the inner cavity is connected to the first opening and the second opening; the medicine containing device is arranged in the inner cavity, and A space close to the first opening and used for carrying drug particles or pills is communicated with the second opening; the diameter of the first opening is smaller than the minimum diameter of the drug containing device.
  • the medicine containing device can be maintained in the inner cavity in any manner without being separated from the second part of the tubular member. Shedding from an opening.
  • the diameter of the second opening is smaller than the smallest diameter of the medicine containing device.
  • the second opening is also provided with a top cover for sealing to ensure that after the oral drug delivery device is loaded with drugs, even if bumps or completely inverted during transportation, there will be more drug particles. The pill will not leak from the second opening.
  • the fourth object of the present invention is to provide a medicine containing device for a solid oral preparation, the structure of which is structure one or structure two:
  • the drug containing device includes a filter member and a support member for supporting the filter member, the filter member and the support member cooperate with each other to form a space for carrying drug particles or multiple pills, so
  • the filter component has one or more pores that allow liquid to pass through;
  • the filter component is also provided with a water-soluble polymer material layer, so that the drug particles or pills cannot pass through;
  • the drug accommodating device is a cylindrical structure with an open top and a screen at the bottom.
  • the inner surface of the screen is provided with a water-soluble polymer material layer, and the tube above the water-soluble polymer material layer
  • the inner cavity of the shaped structure is used to contain drug particles or multiple pills.
  • the filter component is a common type in the field, preferably a filter membrane.
  • the filter membrane is preferably a disc-shaped structure.
  • the thickness of the filter membrane is preferably 0.01 to 0.5 mm, more preferably 0.1 to 0.3 mm, for example 0.2 mm.
  • a water-soluble polymer material layer is arranged on the filter membrane.
  • the material of the filter membrane is a conventional filter membrane material in the field, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyvinyl chloride Ethylene phthalate, cellulose acetate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, glass fiber, nylon, polyethersulfone, polyvinylidene fluoride and polytetrafluoroethylene.
  • the shape of the raw material of the filter membrane includes, but is not limited to, granular, sheet, fibrous, and the like.
  • the shape and structure of the pores in the filter membrane can be conventional regular structures in the art, for example, connecting and penetrating the upper and lower surfaces of the filter membrane in a straight line.
  • the pore size of the filter membrane is conventional in the art, such as 1-500 ⁇ m, preferably 20-400 ⁇ m, more preferably 40-300 ⁇ m, such as 150 ⁇ m, 200 ⁇ m, 250 ⁇ m, 300 ⁇ m.
  • the diameter of the filter membrane can be conventional in the field, and the diameter of the filter membrane is defined as the effective diameter to retain solids and pass liquid.
  • the outermost circle of the filter membrane diameter will be up and down.
  • the support member is pressed in the middle to fix the filter membrane, for example, a membrane with a diameter of 10mm, with 1mm on the side being 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.
  • the preparation process of the filter membrane is a conventional process in the field, including but not limited to sintering, injection molding, pressing, weaving, etc.
  • the forming method of the water-soluble polymer material layer is conventional in the art, preferably: adsorbing, coating or spraying a polymer material solution on the upper surface and/or lower surface of the filter membrane, or
  • the filter membrane is immersed in a polymer material solution and dried. After drying, the polymer materials are dispersed in the membrane pores and membrane materials of the filter membrane to form a framework with a certain hardness, and at the same time block the pores of the filter membrane, so that the drug particles or pellets smaller than or equal to the pore size of the filter membrane are stored and It will not leak during transportation.
  • the structure formed by the water-soluble polymer material layer preferably has the following two types: a continuous layer of water-soluble polymer material is formed on the upper or lower surface of the filter membrane, or the polymer material will be completely blocked
  • the pores of the filter membrane form a complete and dense layer of water-soluble polymer material (for example, the structure is formed by dipping), and it is better to form a continuous water-soluble layer only on the upper or lower surface of the filter membrane.
  • the polymer material layer (for example, the structure is formed by adsorption, coating, or spraying only on a certain surface of the filter membrane), and it is more preferable to form a continuous layer of high water solubility on the lower surface of the filter membrane.
  • Molecular material layer for example, the structure is formed by adsorption, coating, or spraying only on a certain surface of the filter membrane.
  • the dissolution time of the water-soluble polymer material layer is preferably less than or equal to 10s, such as 2s.
  • the patient puts the drug containing device in the liquid to sip, and at the same time, the water-soluble polymer material layer is dissolved in a very short time, and the liquid passes through the drug containing device with very little resistance, and the drug particles or Multiple pills are delivered into the patient's mouth. Because the water-soluble polymer material layer dissolves quickly, the patient does not feel the change in resistance during use.
  • the water-soluble polymer material layer is preferably selected as a polymer material with better water solubility and film-forming properties and a small molecular weight to form a high After the molecular material solution, it is formed through a certain process.
  • the molecular weight of the polymer material is preferably 2,000 to 200,000, more preferably 2,000 to 100,000.
  • the type of the polymer material is preferably selected from hypromellose, copovidone, hydroxypropyl cellulose, hydroxyethyl cellulose (HEC), povidone, polyethylene glycol (PEG), gelatin One or more of, poloxamer, xanthan gum and Eudragit.
  • the preparation method of the polymer material solution is a conventional method in the art, and specifically includes the following steps: mixing the polymer material and the solvent uniformly.
  • the solvent is a volatile solvent that can dissolve polymer materials and is conventional in the art, such as water, ethanol, acetone, and the like.
  • the viscosity of the polymer material solution is a key parameter in the forming process, and the viscosity depends on three parameters, the polymer concentration, molecular weight and chemical structure.
  • the viscosity range is generally 2 centipoise (cP)-5000 centipoise (cP), preferably 2cP-1000cP.
  • the concentration of the polymer material solution is preferably 0.1%-30%, such as 10%, and the concentration is a mass percentage concentration.
  • the weight gain of the polymer material is generally 0.01-60 mg/cm2, preferably 0.5-30 mg/cm2, for example 6.4 mg/cm2.
  • "weight gain of polymer material” means the weight of the water-soluble polymer material layer formed on each square centimeter of the filter element (such as filter membrane) or screen after curing and drying, and the weight unit is in milligrams.
  • a hypromellose E3 solution with a concentration of 10% is selected as the polymer material solution.
  • the support member has a conventional meaning in the art, and its function is to support the filter member without affecting the filterability and liquid permeability of the filter member.
  • the supporting member includes an upper supporting member and a lower supporting member, and the upper supporting member and the lower supporting member can cover each other and clamp the filter member in the middle.
  • the space above the upper support member and the filter member is used for accommodating drug particles or multiple pills. This structure is similar to a sandwich form.
  • the support member includes a filter member accommodating member and a medicine accommodating member, and both the filter member accommodating member and the medicine accommodating member have a hole-like structure end. And an open end, the pore-like structure end has one or more holes that allow liquid to pass through, and the open end of the filter component accommodating component and the pore 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 multiple pills.
  • 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.
  • the size of the pore-like structure of the medicine containing part and the filtering part containing part does not affect the filterability and liquid permeability of the filtering part.
  • the material of the supporting member 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, poly Tetrafluoroethylene, polyethylene terephthalate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, ceramics, silicon dioxide, silicone.
  • the preparation process of the supporting member is conventional in the art, including but not limited to sintering, injection molding and the like.
  • the material and preparation process of the cylindrical structure are the same as the description of the support part.
  • the size of the mesh is conventional in the art, for example, 200 ⁇ m.
  • the drug particles or pellets have conventional meanings in the art, and generally refer to particles, powders or pellets containing active pharmaceutical ingredients.
  • the particle size of the drug particles or pellets is conventional in the art, and is generally 1-5000 ⁇ m, preferably 25-2000 ⁇ m, and more preferably 50-1000 ⁇ m.
  • the pore size of the filter element in the first structure or the sieve in the second structure is 40-300 ⁇ m.
  • the active pharmaceutical ingredients contained in the pharmaceutical particles or pills 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, Fuppin, sulfasalazine, acetaminophen, dextromethorphan, doxylamine, pseudoephedrine, diphenhydramine, amphetamine, methylphenidate, deferasirox, ivacaftor, lumacaftor, tacrolimus, dichloromethane Zepam, clobazam, vigabatrin, bosentan, melatonin, biotin, disodium dimercaptos, am
  • the preparation process of the drug particles or multiple 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, pellet spraying Apply medicine.
  • 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 further includes a tubular member with openings at both ends And an inner cavity, one end of which is a first opening, and the other end is a second opening, the inner cavity is connected to the first opening and the second opening; the medicine containing device circumscribes the free space of the first opening And the space used to carry the drug particles or multiple pills is connected to the inner cavity.
  • 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.
  • the particles or pellets containing the active drug ingredient are placed in the cavity of the drug containing device.
  • one end of the supporting member contacts the liquid, and the liquid is sucked into the tubular member through the filter member by sipping.
  • the particles or pellets of the active pharmaceutical ingredient enter the tubular member with the liquid, and then into the mouth.
  • the second opening is also provided with a top cover for sealing to ensure that after the oral drug delivery device is loaded with drugs, even if bumps occur or are completely inverted during transportation, the drug particles may be too large. The pill will not leak from the second opening.
  • the tubular member is a straight straw.
  • the straight straw has at least one fold structure.
  • the corrugated portion structure has a pair of wings and a turning end; the corrugated portion structure can be stretched or contracted along the axial direction of the tubular member, and forms turbulence during stretching.
  • the tubular component has at least two pipe sections, and the pipe sections are connected in a sealed manner and can be stretched or contracted along the axial direction of the tubular member; the tubular member is in a stretched state At this time, a turbulence generating part having at least one step structure is formed.
  • the inner diameter of the first pipe section in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe section, and the outer diameter of the second pipe section is smaller than that of the third pipe section.
  • the inner diameter of the first pipe section, and each pipe section can be stretched or contracted along the axial direction of other pipe sections; or, the inner diameter of the first pipe section and the second pipe section in the direction from the first opening to the second opening
  • the outer diameter, inner diameter, and outer diameter of the third pipe section gradually decrease, and each pipe section can be stretched or contracted along the axis of other pipe sections.
  • the inner diameter of the first pipe section in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe section
  • the inner diameter of the second pipe section is the same as that of the fourth pipe section.
  • the inner diameters of the pipe sections are the same, wherein the inner diameter of the second pipe section is smaller than the first pipe section, and each pipe section can be stretched or contracted in the axial direction of other pipe sections; or, it extends from the first opening to the second pipe section.
  • the inner diameters of the first pipe section to the fourth pipe section in the opening direction gradually decrease, and each pipe section can be stretched or contracted along the axial direction of the other pipe sections.
  • 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 further includes a tubular member with openings at both ends And an inner cavity, one end of which is a first opening, and the other end is a second opening, the inner cavity is connected to the first opening and the second opening; the medicine containing device is arranged in the inner cavity, and A space close to the first opening and used for carrying drug particles or pills is communicated with the second opening; the diameter of the first opening is smaller than the minimum diameter of the drug containing device.
  • the medicine containing device by restricting the diameter of the first opening to be smaller than the minimum diameter of the medicine containing device, the medicine containing device can be maintained in the inner cavity in any manner without being separated from the second part of the tubular member. Shedding from an opening.
  • the diameter of the second opening is smaller than the minimum diameter of the medicine containing device.
  • the second opening is also provided with a top cover for sealing to ensure that after the oral drug delivery device is loaded with drugs, even if bumps occur or are completely inverted during transportation, the drug particles may be too large. The pill will not leak from the second opening.
  • the seventh object of the present invention is to provide a medicine containing device for a solid oral preparation, which comprises a filter part and a support part for supporting the filter part, and the filter part and the support part cooperate with each other to form A space for carrying drug particles or multiple pills, the filter component has one or more pores that allow liquid to pass through; the pores are distributed in an intricately intersecting manner inside the filter component, and the filter component is also provided with a The water-soluble polymer material layer prevents the drug particles or pellets from passing through.
  • the mechanism of this solution is: because the particle size distribution of the drug particles or multi-pills is within a range, due to the limitation of the process, it is impossible to eliminate all the particles or multi-pills smaller than a certain size. In this case, in order to ensure that the sip Smaller resistance, a relatively large pore size will be selected when setting up and down intricately crossing pore structures. In order to meet the requirements of no leakage, it is necessary to set the filter components (such as filter membranes) as up and down intricately crossing pore structures. , Setting a water-soluble polymer material layer on the filter membrane.
  • the filter component is a common type in the field, preferably a filter membrane.
  • the filter membrane is preferably a cylindrical structure.
  • the thickness of the filter membrane is preferably 0.3-20 mm, more preferably 0.5-15 mm, still more preferably 0.5-10 mm, for example 2 mm.
  • the filter membrane has a certain thickness, so the pores of the filter membrane are arranged in an intricately intersecting structure, preferably the upper and lower surfaces of the filter membrane and the inner pores are arranged in an irregular and intricate structure, For example, a sponge-like porous structure, or a fluffy structure formed by multiple layers of fibers randomly stacked and pressed.
  • the material of the filter membrane is a conventional filter membrane material in the field, including but not limited to one or more of the following materials: polypropylene, polyethylene, polyvinyl chloride, polyvinylidene chloride, polyvinyl chloride Ethylene phthalate, cellulose acetate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, glass fiber, nylon, polyethersulfone, polyvinylidene fluoride and polytetrafluoroethylene.
  • the shape of the raw material of the filter membrane includes, but is not limited to, granular, sheet, fibrous, and the like.
  • the shape and structure of the pores in the filter membrane can be conventional regular structures in the art, for example, connecting and penetrating the upper and lower surfaces of the filter membrane in a straight line.
  • the pore size of the filter membrane is conventional in the art, such as 1-500 ⁇ m, preferably 20-400 ⁇ m, more preferably 40-300 ⁇ m, such as 150 ⁇ m, 200 ⁇ m, 250 ⁇ m, 300 ⁇ m.
  • the diameter of the filter membrane can be conventional in the field, and the diameter of the filter membrane is defined as the effective diameter to retain solids and pass liquid.
  • the outermost circle of the filter membrane diameter will be up and down.
  • the support member is pressed in the middle to fix the filter membrane, for example, a membrane with a diameter of 10mm, with 1mm on the side being 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.
  • the preparation process of the filter membrane is a conventional process in the field, including but not limited to sintering, injection molding, pressing, weaving, etc.
  • the forming method of the water-soluble polymer material layer is conventional in the art, preferably: adsorbing, coating or spraying a polymer material solution on the upper surface and/or lower surface of the filter membrane, or
  • the filter membrane is immersed in a polymer material solution and dried. After drying, the polymer materials are dispersed in the membrane pores and membrane materials of the filter membrane to form a framework with a certain hardness, and at the same time block the pores of the filter membrane, so that the drug particles or pellets smaller than or equal to the pore size of the filter membrane are stored and It will not leak during transportation.
  • the structure formed by the water-soluble polymer material layer preferably has the following two types: a continuous layer of water-soluble polymer material is formed on the upper or lower surface of the filter membrane, or the polymer material will be completely blocked
  • the pores of the filter membrane form a complete and dense layer of water-soluble polymer material (for example, the structure is formed by dipping), and it is better to form a continuous water-soluble layer only on the upper or lower surface of the filter membrane.
  • the polymer material layer (for example, the structure is formed by adsorption, coating, or spraying only on a certain surface of the filter membrane), and it is more preferable to form a continuous layer of high water solubility on the lower surface of the filter membrane.
  • Molecular material layer for example, the structure is formed by adsorption, coating, or spraying only on a certain surface of the filter membrane.
  • the dissolution time of the water-soluble polymer material layer is preferably less than or equal to 10s, such as 2s.
  • the patient puts the drug containing device in the liquid to sip, and 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 to deliver the drug particles Into the patient's mouth. Because the water-soluble polymer material layer dissolves quickly, the patient does not feel the change in resistance during use.
  • the molecular weight of the polymer material is generally 2,000 to 200,000, preferably 2,000 to 100,000. More preferably, the type of polymer material is selected from hypromellose (HPMC), copovidone, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), povidone, polyethylene One or more of glycol (PEG), gelatin, poloxamer, xanthan gum, and Eudragit.
  • the preparation method of the polymer material solution is a conventional method in the art, and specifically includes the following steps: mixing the polymer material and the solvent uniformly.
  • the solvent is a volatile solvent that can dissolve polymer materials and is conventional in the art, such as water, ethanol, acetone, and the like.
  • the viscosity of the polymer material solution is a key parameter in the forming process, and the viscosity depends on three parameters, the polymer concentration, molecular weight and chemical structure.
  • the viscosity range is generally 2 centipoise (cP)-5000 centipoise (cP), preferably 2cP-1000cP.
  • the concentration of the polymer material solution is preferably 0.1%-30%, such as 10%, and the concentration is a mass percentage concentration.
  • the weight gain of the polymer material is generally 0.01-60 mg/cm2, preferably 0.5-30 mg/cm2, for example 6.4 mg/cm2.
  • a hypromellose E3 solution with a concentration of 10% is selected as the polymer material solution.
  • the support member has a conventional meaning in the art, and its function is to support the filter member without affecting the filterability and liquid permeability of the filter member.
  • the supporting member includes an upper supporting member and a lower supporting member, and the upper supporting member and the lower supporting member can cover each other and clamp the filter member in the middle.
  • the space above the upper support member and the filter member is used for accommodating drug particles or multiple pills. This structure is similar to a sandwich form.
  • the supporting member includes a filter member accommodating member and a medicine accommodating member, and both the filter member accommodating member and the medicine accommodating member have a hole-like structure end. And an open end, the pore-like structure end has one or more holes that allow liquid to pass through, and the open end of the filter member accommodating member and the pore-like structure end of the drug accommodating member can be covered to form A cavity containing the filter component; the open end of the drug containing component is an open tubular structure for accommodating drug particles or multiple pills.
  • 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.
  • the size of the pore structure of the drug accommodating member and the filter accommodating member does not affect the filterability and liquid permeability of the filter member.
  • the material of the supporting member 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, poly Tetrafluoroethylene, polyethylene terephthalate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, ceramics, silicon dioxide, silicone.
  • the preparation process of the supporting member is conventional in the art, including but not limited to sintering, injection molding and the like.
  • the drug particles or pellets have conventional meanings in the art, and generally refer to particles, powders or pellets containing active pharmaceutical ingredients.
  • the particle size of the drug particles or pellets is conventional in the art, and is generally 1-5000 ⁇ m, preferably 25-2000 ⁇ m, and more preferably 50-1000 ⁇ m.
  • the pore size of the filter component is 40-300 ⁇ m.
  • the active pharmaceutical ingredients contained in the pharmaceutical particles or pills 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, Fuppin, sulfasalazine, acetaminophen, dextromethorphan, doxylamine, pseudoephedrine, diphenhydramine, amphetamine, methylphenidate, deferasirox, ivacaftor, lumacaftor, tacrolimus, dichloromethane Zepam, clobazam, vigabatrin, bosentan, melatonin, biotin, disodium dimercaptos, am
  • the preparation process of the drug particles or multiple 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, pellet spraying Apply medicine.
  • the eighth object of the present invention is to provide an oral drug delivery device, which includes the drug containing device of the seventh object, and the oral drug delivery device further includes a tubular member with openings at both ends And an inner cavity, one end of which is a first opening, and the other end is a second opening, the inner cavity is connected to the first opening and the second opening; the medicine containing device circumscribes the free space of the first opening And the space used to carry the drug particles or multiple pills is connected to the inner cavity.
  • the drug accommodating device is placed outside the tubular member, and is preferably maintained at the first opening outside the tubular member by means of a fixed sleeve or threaded connection.
  • the particles or pellets containing the active drug ingredient are placed in the cavity of the drug containing device.
  • one end of the supporting member contacts the liquid, and the liquid is sucked into the tubular member through the filter member by sipping.
  • the particles or pellets of the active pharmaceutical ingredient enter the tubular member with the liquid, and then into the mouth.
  • the second opening is also provided with a top cover for sealing to ensure that after the oral drug delivery device is loaded with drugs, even if bumps occur or are completely inverted during transportation, the drug particles may be too large. The pill will not leak from the second opening.
  • the tubular member is a straight straw.
  • the straight straw has at least one fold structure.
  • the corrugated portion structure has a pair of wings and a turning end; the corrugated portion structure can be stretched or contracted along the axial direction of the tubular member, and forms turbulence during stretching.
  • the tubular component has at least two pipe sections, and the pipe sections are connected in a sealed manner and can be stretched or contracted along the axial direction of the tubular member; the tubular member is in a stretched state At this time, a turbulence generating part having at least one step structure is formed.
  • the inner diameter of the first pipe section in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe section, and the outer diameter of the second pipe section is smaller than that of the third pipe section.
  • the inner diameter of the first pipe section, and each pipe section can be stretched or contracted along the axial direction of other pipe sections; or, the inner diameter of the first pipe section and the second pipe section in the direction from the first opening to the second opening
  • the outer diameter, inner diameter, and outer diameter of the third pipe section gradually decrease, and each pipe section can be stretched or contracted along the axis of other pipe sections.
  • the inner diameter of the first pipe section in the direction from the first opening to the second opening is the same as the inner diameter of the third pipe section
  • the inner diameter of the second pipe section is the same as that of the fourth pipe section.
  • the inner diameters of the pipe sections are the same, wherein the inner diameter of the second pipe section is smaller than the first pipe section, and each pipe section can be stretched or contracted in the axial direction of other pipe sections; or, it extends from the first opening to the second pipe section.
  • the inner diameters of the first pipe section to the fourth pipe section in the opening direction gradually decrease, and each pipe section can be stretched or contracted along the axial direction of the other pipe sections.
  • the ninth object of the present invention is to provide an oral drug delivery device, which includes the drug containing device of the seventh object, and the oral drug delivery device further includes a tubular member with openings at both ends And an inner cavity, one end of which is a first opening, and the other end is a second opening, the inner cavity is connected to the first opening and the second opening; the medicine containing device is arranged in the inner cavity, and A space close to the first opening and used for carrying drug particles or pills is communicated with the second opening; the diameter of the first opening is smaller than the minimum diameter of the drug containing device.
  • the medicine containing device by restricting the diameter of the first opening to be smaller than the minimum diameter of the medicine containing device, the medicine containing device can be maintained in the inner cavity in any manner without being separated from the second part of the tubular member. Shedding from an opening.
  • the diameter of the second opening is smaller than the minimum diameter of the medicine containing device.
  • the second opening is also provided with a top cover for sealing to ensure that after the oral drug delivery device is loaded with drugs, even if bumps occur or are completely inverted during transportation, the drug particles may be too large. The pill will not leak from the second opening.
  • first opening “second opening”, “first pipe section”, “second pipe section”, “third pipe section”, “fourth pipe section”, etc.
  • the description is for the convenience of explanation, and should not be construed as a limitation on a specific position or sequence.
  • the positive progress effect of the present invention is that: the drug containing device of the present invention can better solve the problem of drug particle leakage and large fluid resistance during sipping, and the oral drug delivery device formed by matching the tubular member can be used as a direct contact drug
  • the medicine packaging material is used and has a storage function.
  • Fig. 1 is a schematic diagram of the structure of the support member and the filter member in the medicine containing device of embodiment 1, 1a is the lower support member, 1b is the filter member, and 1c is the upper support member;
  • FIG. 2 is a schematic diagram of the assembly of the supporting part and the filter part in the medicine containing device of embodiment 1, 2a is before assembly, and 2b is after assembly;
  • FIG. 3 is a schematic structural diagram of a built-in oral drug delivery device formed after assembly of the drug containing device and the straw of Embodiment 1;
  • Figure 4 is a structural schematic diagram of the support part and the filter part of the medicine containing device of embodiment 2, 4a is a cage support part, 4b is a filter part, and 4c is an upper cover of the cage support part;
  • FIG. 5 is a schematic diagram of the assembly of the supporting part and the filter part of the medicine containing device of Embodiment 2;
  • FIG. 6 is a schematic diagram of a built-in oral drug delivery device formed after assembly of the drug containing device and the straw of Embodiment 2;
  • Figure 7 is a schematic diagram of the built-in oral drug delivery device of Examples 1 to 3 when the straw is used, 7a is before sipping, and 7b is after sipping;
  • 8 is a structural schematic diagram of the filter component accommodating component, the filter component, and the drug accommodating component in the drug accommodating device of Embodiment 4.
  • 8a is the filter component accommodating component
  • 8b is the filter component
  • 8c is the drug accommodating component;
  • Figure 9 is a schematic diagram of the assembly of the filter component accommodating component, the filter component and the drug accommodating component in the drug accommodating device of Embodiment 4.
  • 9a is before assembly, and 9b is after assembly;
  • FIG. 10 is a schematic diagram of an external oral drug delivery device formed after assembly of the drug containing device and the straw of Embodiment 4; FIG.
  • 11 is a schematic diagram of the external oral drug delivery device of Example 4 when the straw is in use, 11a is before sip, and 11b is after sip;
  • Figure 12 is a cross-sectional view of an irregular and intricate cross-section of the internal pores of the filter element in the embodiment
  • FIG. 13 is a schematic diagram of the structure of the medicine containing device of Embodiment 8.
  • Example 14 is a schematic diagram of the structure of the oral drug delivery device of Example 8.
  • the above filter membrane was soaked in a 10% hypromellose E3 solution, and then placed in an oven to dry. After drying (weight gain is 6.4mg/cm 2 ), place it between two polyethylene discs with a diameter of 1cm and a thickness of 3mm. The two polyethylene discs are covered with a 2mm ⁇ 2mm transparent net. grid.
  • One of the polyethylene discs has four protrusions with a diameter of 2mm on the surface, and the symmetrical position on the surface of the other polyethylene disc is four pits with a diameter of 2mm.
  • the two discs are mechanically condensed by the concave-convex structure to filter
  • the membrane is tightly fixed in the middle to form a medicine containing device. This device is placed in a wrinkled straw with an inner diameter of 1.05 cm from the nozzle at the end that is in contact with the liquid, and the nozzle is twisted so that the drug containing device can stay in the straw.
  • the filter membrane with a pore size of 300 ⁇ m, a thickness of 6mm and a material made of polypropylene (the filter membrane is provided with intricate and irregular pores) (Figure 12 is the filter part of Figure 4 and Figure 8 Schematic diagram of the internal channel structure), cut into a cylinder with a diameter of 8mm.
  • the mechanical condensation is fixed with the cylinder body, and the filter membrane is wrapped in it to form a drug containing device.
  • the device is placed in a wrinkled straw with an inner diameter of 1.2 cm from the nozzle at the end that is in contact with the liquid, and the nozzle is twisted so that the drug containing device can stay in the straw.
  • the above filter membrane was soaked in a 10% hypromellose E3 solution, and then placed in an oven to dry. After drying (weight gain is 25.5mg/cm 2 ), place it between two polyethylene discs with a diameter of 1cm and a thickness of 3mm. The two polyethylene discs are covered with a 2mm ⁇ 2mm transparent net. grid.
  • One of the polyethylene discs has four protrusions with a diameter of 2mm on the surface, and the symmetrical position on the surface of the other polyethylene disc is four pits with a diameter of 2mm.
  • the two discs are mechanically condensed by the concave-convex structure to filter
  • the membrane is tightly fixed in the middle to form a medicine containing device. This device is placed in a wrinkled straw with an inner diameter of 1.05 cm from the nozzle at the end that is in contact with the liquid, and the nozzle is twisted so that the drug containing device can stay in the straw.
  • FIG. 7 The schematic diagrams of the structures of the devices of Examples 1, 2 and 3 in use are shown in FIG. 7.
  • the injection molding process is used to prepare the accommodating part of the filter part and the medicine accommodating part.
  • the above-mentioned filter component accommodating component is a cylindrical structure with an inner diameter of 12.1mm and an internal height of 4mm, and the bottom of the cylinder has a circular hole with a diameter of 8mm from top to bottom; the above-mentioned drug accommodating component has an inner diameter of 9.1mm and an internal height of 1.5cm
  • the cylindrical structure is a cylindrical structure with an inner diameter of 12.1mm and an internal height of 4mm, and the bottom of the cylinder has a circular hole with a diameter of 8mm from top to bottom; the above-mentioned drug accommodating component has an inner diameter of 9.1mm and an internal height of 1.5cm The cylindrical structure.
  • 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, and the two are condensed through a mechanical structure, and the filter membrane is fixed in the middle to obtain the drug accommodating device. Then connect the upper end of the drug containing device to the nozzle of the liquid-contacting end with a corrugated straw (inner diameter of 8.6 mm). Fill 504.1mg hot-melt granulated dabigatran etexilate mesylate particles (containing 75mg dabigatran etexilate, particle size distribution see Table 1) through the upper end of the straw into the above-mentioned drug containing device, and no particles pass through the drug container. The device leaks.
  • Particle size range percentage >355 ⁇ m 23.8% 250-355 ⁇ m 7.6% 180-250 ⁇ m 35.9% 180 ⁇ m 32.7%
  • a filter membrane with a pore size of 300 ⁇ m, a thickness of 1.5 mm and a material made of polypropylene is provided with intricate and irregular pores and cut into a disc with a diameter of 12 mm.
  • the filter membrane was soaked in a 10% Killidon VA64 (copovidone) ethanol solution, and then placed in an oven to dry, and the weight gain after drying was 16.0 mg/cm 2 .
  • the injection molding process is used to prepare the accommodating part of the filter part and the medicine accommodating part.
  • the above-mentioned filter component accommodating component is a cylindrical structure with an inner diameter of 12.1mm and an internal height of 4mm, and the bottom of the cylinder has a circular hole with a diameter of 8mm, which is transparent up and down;
  • the cylindrical structure 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, and the two are condensed through a mechanical structure, and the filter membrane is fixed in the middle to obtain the drug accommodating device. Then connect the upper end of the drug containing device to the mouth of the liquid-contacting end with a corrugated straw (inner diameter of 8.6 mm).
  • a 500 mg D-mannitol pellet core with a particle size ranging from 75 ⁇ m to 150 ⁇ m was filled into the cylinder of the drug containing device through the upper end of the straw, and no pellets leaked through the drug containing device.
  • a filter membrane with a pore size of 250 ⁇ m, a thickness of 0.3 mm, and a material made of polypropylene was cut into discs with a diameter of 12 mm.
  • the filter membrane was soaked in 10% Killidon VA64 (copovidone) ethanol solution, and then dried in an oven. After drying, the weight gain was 8.9 mg/cm 2 .
  • the injection molding process is used to prepare the accommodating part of the filter part and the medicine accommodating part.
  • the above-mentioned filter component accommodating component is a cylindrical structure with an inner diameter of 12.1mm and an internal height of 3mm, and the bottom of the cylinder has a circular hole with a diameter of 8mm that is transparent from top to bottom; the above-mentioned drug accommodating component has an inner diameter of 9.1mm and an internal 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, and the two are condensed through a mechanical structure, and the filter membrane is fixed in the middle to obtain the drug accommodating device. Then connect the upper end of the drug containing device to the mouth of the liquid-contacting end with a corrugated straw (inner diameter of 8.6 mm).
  • Embodiment 7 (intricate cross tunnel structure + external)
  • the drug containing device in Example 4 was assembled with a straw with a total length of 20 cm, an inner diameter of 8.6 mm, and a wrinkle length of 4 cm.
  • the lower end of the drug containing device is blocked with fingers, and the suction tube is filled with liquid from the upper end. Under the action of gravity, the emptying time of the liquid in the device is about 2 seconds to 3 seconds.
  • an injection molding process is used to prepare the drug containing device.
  • the above-mentioned 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, with a plurality of screens with upper and lower permeable apertures of 200 ⁇ m; the inner wall of the cylinder mouth is designed with two circles of convex
  • the ring structure is used to connect the straws externally.
  • the 7.5% HPMC E3 aqueous solution was coated on the inner surface of the bottom of the cylinder and dried, and the weight gain was 17.7 mg/cm 2 to obtain a drug containing device.
  • a filter membrane with a pore size of 100 ⁇ m, a thickness of 2 mm and a material of polypropylene (the filter membrane is provided with intricate and irregular pores) is cut into a disc with a diameter of 16 mm.
  • the injection molding process is used to prepare the accommodating part of the filter part and the medicine accommodating part.
  • the above-mentioned filter component accommodating component is a cylindrical structure with an inner diameter of 16.1mm and an internal height of 4mm, and the bottom of the cylinder has a circular hole with a diameter of 12mm that is transparent from top to bottom; the above-mentioned drug accommodating component has an internal diameter of 12.5mm and an internal height of 1.5cm
  • the cylindrical structure is a cylindrical structure with an inner diameter of 16.1mm and an internal height of 4mm, and the bottom of the cylinder has a circular hole with a diameter of 12mm that is transparent from top to bottom; the above-mentioned drug accommodating component has an internal diameter of 12.5mm and an internal height of 1.5cm The cylindrical structure.
  • 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, and the two are condensed through a mechanical structure, and the filter membrane is fixed in the middle to obtain the drug accommodating device. Then connect the upper end of the drug containing device to the mouth of the liquid-contacting end with a corrugated straw (inner diameter of 12 mm).
  • a corrugated straw inner diameter of 12 mm.
  • Fill 320mg omeprazole enteric-coated multiple pills containing 20mg omeprazole
  • 1334mg amoxicillin granules containing 1000mg amoxicillin
  • 840mg clarithromycin granules containing 500mg clarithromycin
  • omeprazole enteric-coated multi-pill In the accommodating device, no multiple pills or particles leak through the drug accommodating device.
  • the end of the straw with the drug accommodating device is placed in the liquid, and the patient sucks the liquid into the straw.
  • the liquid easily passes through the drug accommodating device and pushes the multiple pills into the patient's mouth to complete the medication.
  • the particle size range of omeprazole enteric-coated multi-pill is 0.25-0.355mm. See Table 2 and Table 3 for the particle size distribution of amoxicillin particles and clarithromycin particles.
  • Embodiment 10 (intricate cross tunnel structure + built-in)

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Abstract

一种固体口服制剂的药物容置装置及含其的口服给药递送装置，该药物容置装置包括过滤部件和支撑部件，过滤部件和支撑部件相互配合形成用于承载药物颗粒或多丸的空间，过滤部件具有一个或多个允许液体通过的孔道；孔道在过滤部件的内部以上下错综交叉的方式分布，和/或，过滤部件上设有一水溶性高分子材料层。或者，药物容置装置为顶端开口、底部为筛网的筒状结构，筛网的内表面设有一水溶性高分子材料层，其上方的筒状结构的内腔用于容纳药物颗粒或多丸。该药物容置装置能够克服药物颗粒或多丸泄漏和啜吸时流体阻力大的问题。

Description

固体口服制剂的药物容置装置及含其的口服给药递送装置
本申请要求申请日为2019/9/30的中国专利申请CN201910939687.8和申请日为2019/9/30的中国专利申请CN201921652286.6的优先权。本申请引用上述中国专利申请的全文。
技术领域
本发明涉及医疗器械领域，尤其涉及一种固体口服制剂的药物容置装置及含其的口服给药递送装置。
背景技术
片剂和胶囊是最方便和容易接受的口服剂型。但是一些病人，特别是儿童和老人，通常难以吞咽大尺寸的药片和胶囊；有些病人因不可接受的口感而不愿意服用这种药物。因此，现有技术提出了各种给药装置，其能促进大尺寸片剂和胶囊的吞咽，并尽可能减少患者对给药剂量和味觉的感知。各种给药装置中，均涉及到能够容纳和贮存药物的药物容置部件，以下与啜吸装置药物容置部件相关的专利和申请通过引用结合于此。
EP 0383503 A1描述了一种改进的装置，该装置的药物容置部件为筛网，该筛网的表面积大于管的内腔横截面积，其用于将单位剂量的治疗剂保持和定位在管中，该装置适应于通过患者的正常啜吸动作将液体流通过管输送该剂量。
美国专利6096003描述了一种啜吸装置，该装置的药物容置部件为塞子，该塞子可以用于容置活性药物成分，并通过液体带动塞子在管腔内向上滑动，从而完成药物的递送。
美国专利6109538揭示了一种啜吸装置，该装置的容置部件为一对具长方形网格的筛网，设置在管腔中，用于限制调味对象。
美国专利6333050 B2描述了一种啜吸装置，该装置的药物容置部件为单向阀，非啜吸状体时用于容置药物，啜吸状态时发生形变，允许液体通过。
美国专利8334003 B2描述了一种啜吸装置，其包括细长管状构件，在管状构件的每一端具有一对过滤装置，以将调味颗粒保持在过滤装置内，从而通过正常抽吸使调味剂进入普通饮料中。
美国专利6224908 B1描述了一种具有流体控制器的活性药物成分的递送装置。所述的流体控制器为多孔塞，其与管壁摩擦小，非啜吸状态容置药物，啜吸时在流体的推动 下，加速将药物递送至患者口内。
上述专利所涉及的药物容置部件，在实际应用时会产生诸多问题。众所周知，通过湿法制粒、干法制粒、挤出滚圆、熔融制粒等工艺制备的含有API的颗粒或多丸，一般具有相对较宽的粒径分布，既有比平均粒径大很多的颗粒或多丸，也有比平均粒径小很多的细粉颗粒和多丸。因此对于药物容置部件的功能，一方面，要求液体能够顺利通过药物容置部件且阻力很小，患者啜吸时不费力；同时要求药物容置部件的孔径，小于所有颗粒或者多丸的直径，保证颗粒或多丸不会通过药物容置部件泄漏。这两个需求本身是相悖的，保证孔径足够大，液体通过的阻力才小；但孔径越大，则粒径较小的颗粒和多丸泄漏的概率就越大。这样就限制了应用范围，含有粒径小于等于药物容置部件孔径的颗粒或者多丸的物料无法使用此装置，除非通过人为的筛分，这样降低了收率，增加了成本。
发明内容
本发明所要解决的技术问题在于克服现有技术中的促进药物吞咽的装置存在的药物颗粒或多丸泄漏和啜吸时流体阻力大的缺陷，而提供了一种固体口服制剂的药物容置装置及含其的口服给药递送装置。本发明的药物容置装置在使用时与吸管作为一个整体，用于容纳粒径大于、等于或小于药物容置装置孔径的含有活性药物成分的颗粒或多丸。
本发明的发明人在研发之初就发现，降低液体阻力和降低药物泄漏是一个从理论上讲相反的命题，很难做到平衡，因而本发明的技术难点在于找到一种合理的解决方案，既要保证液体阻力小，又要保证承载的颗粒和多丸不泄漏。
从机理上看，本发明允许容置粒径小于等于过滤部件孔径的药物颗粒或多丸的机理有两个：一种是通过过滤部件内不规则交错的孔道，将细小颗粒截留在过滤部件内，这种过滤部件要求要有一定的厚度，例如厚度为0.5mm以上；另一种是通过水溶性的高分子材料，在过滤部件上形成膜，堵住过滤部件的孔眼，当啜吸时，高分子材料瞬间溶解，水流通过，带动药物进入患者口中，此种机理对过滤部件的厚度没有要求。
本发明的目的之一在于提供一种固体口服制剂的药物容置装置，其包括一过滤部件和用于支撑所述过滤部件的支撑部件，所述过滤部件和所述支撑部件相互配合形成用于承载药物颗粒或多丸的空间，所述过滤部件具有一个或多个允许液体通过的孔道；所述过滤部件的厚度为0.5mm以上时，所述孔道在所述过滤部件的内部以上下错综交叉的方式分布，从而使所述药物颗粒或多丸无法通过。
以下，对将所述过滤部件的孔道设置为上下错综交叉的结构的方式进行具体说明：
本发明中，所述的过滤部件为本领域常见的类型，较佳地为一滤膜。所述滤膜的形状较佳地为圆柱状结构。所述滤膜的厚度较佳地为0.5～20mm，更佳地为0.5～15mm，进一步更佳地为0.5～10mm，例如2mm。
也就是说，滤膜具有一定的厚度，因此将滤膜的孔道设置为上下错综交叉的结构，优选是将滤膜的上下表面以及内部的孔道都设置为不规则的、且错综交叉的结构，例如海绵状的多孔结构，或者由多层纤维无规则层叠排列、压制而成的蓬松结构。这样即使药物颗粒或多丸的粒径小于或等于滤膜的孔径，也不会像通过筛网那样直接通过药物容置装置。由于滤膜孔道的曲折和错综交叉，粒径很小的药物颗粒或多丸会堆积在其表面和内部。当液体通过时，把堆积在滤膜的表面和内部的药物颗粒或多丸递送入患者口中。
以下，对过滤部件(例如滤膜)的材质、孔径、制备工艺的设置条件进行具体说明：
其中，所述的滤膜的材质为本领域常规的滤膜材质，包括但不限于以下材质中的一种或多种：聚丙烯、聚乙烯、聚氯乙烯、聚偏二氯乙烯、聚对苯二甲酸乙二酯、醋酸纤维素、聚乳酸、聚羟基乙酸、聚乳酸-羟基乙酸共聚物、玻璃纤维、尼龙、聚醚砜、聚偏氟乙烯和聚四氟乙烯。
其中，所述滤膜的原材料的形状为本领域常规，包括但不限于颗粒状，片状，纤维状等。
其中，所述的滤膜的孔径大小为本领域常规，例如1-500μm，优选为20～400μm，更优选为40-300μm，例如150μm，200μm，250μm，300μm。
其中，所述的滤膜的直径可为本领域常规，滤膜的直径定义为发挥截留固体和通过液体的有效直径，出于设计和安装工艺的考虑，滤膜直径的最外圈若被用于固定滤膜的上下支撑部件压在中间，例如10mm直径的膜，边上1mm被支撑部件压边，有效直径只有8mm。滤膜常用的有效直径范围一般为4-20mm，较佳地为6-15mm，更佳地为8mm-12mm，例如为10mm。
其中，所述的滤膜的制备工艺为本领域常规工艺，包括但不限于烧结，注塑，压制，编织等。
以下，对支撑部件的结构进行具体说明：
本发明中，所述支撑部件具有本领域常规含义，其作用在于能支撑所述过滤部件、但不影响所述过滤部件的过滤性和透液性。其结构较佳地为：设置在所述过滤部件的上下表面、将所述过滤部件夹持在中间，即类似三明治形式将所述过滤部件夹在中间；或以笼状结构将所述过滤部件包裹在内部。
在本申请一较佳实施方式中，所述支撑部件包括一上支撑部件、一下支撑部件，所 述上支撑部件和所述下支撑部件可相互盖合、并将所述过滤部件夹持在中间，所述上支撑部件与所述过滤部件的上方空间用于容纳药物颗粒或多丸。这种结构类似三明治形式。
在本申请另一较佳实施方式中，所述支撑部件包括一过滤部件容置部件和一药物容置部件，所述过滤部件容置部件和所述药物容置部件均具有一孔状结构端和一开放端，所述孔状结构端具有一个或多个允许液体通过的孔，所述过滤部件容置部件的开放端与所述药物容置部件的孔状结构端可盖合形成用于容纳所述过滤部件的腔体；所述药物容置部件的开放端为开口的管状结构，用于容纳药物颗粒或多丸。本领域技术人员均应理解，本实施方式中过滤部件容置部件的实际功能为与药物容置部件形成腔体，用于容纳过滤部件，这种结构也类似三明治形式。另外药物容置部件和过滤部件容置部件的孔状结构的尺寸不影响所述过滤部件的过滤性和透液性。
在本申请另一较佳实施方式中，所述支撑部件包括一开口向上的笼状支撑部件和一与所述笼状支撑部件配合的上盖，所述上盖上开有供药物颗粒或多丸以及液体流通的孔道，所述笼状支撑部件和所述上盖可围合形成一个中空空间、并将所述过滤部件限制在该空间中，所述上盖与所述过滤部件的上方空间用于容纳药物颗粒或多丸。这种结构类似笼状结构的形式。
其中，所述支撑部件的材质为本领域常规材质，包括但不限于以下材质中的一种或多种：聚丙烯、聚乙烯、聚氯乙烯、聚偏二氯乙烯、聚偏氟乙烯、聚四氟乙烯、聚对苯二甲酸乙二酯、聚乳酸、聚羟基乙酸、聚乳酸-羟基乙酸共聚物、陶瓷、二氧化硅、有机硅。
其中，所述支撑部件的制备工艺为本领域常规，包括但不限于烧结，注塑成型等。
以下，对药物颗粒或多丸的形态和种类进行具体说明：
本发明中，所述药物颗粒或多丸具有本领域常规含义，一般是指含有活性药物成分的颗粒、粉末或多丸。
其中，所述药物颗粒或多丸的粒径为本领域常规，一般为1-5000μm，优选为25-2000μm，更优选为50-1000μm。
较佳地，当所述药物颗粒或多丸的粒径范围为50-1000μm时，所述过滤部件的孔径为40-300μm。
其中，所述药物颗粒或多丸包含的活性药物成分为本领域常规，包括但不限于以下的一种或多种：达比加群酯或其药学上可接受的盐(例如甲磺酸达比加群酯)、阿哌沙班、利伐沙班、左旋多巴-卡比多巴、孟鲁司特、兰索拉唑、奥美拉唑、埃索美拉唑、阿莫西林、克拉霉素、阿奇霉素、甲硝唑、利福平、柳氮磺吡啶、对乙酰氨基酚、右美沙芬、 多西拉敏、伪麻黄碱、苯海拉明、安非他命、哌甲酯、地拉罗司、ivacaftor、lumacaftor、他克莫司、地西泮、氯巴占、氨己烯酸、波生坦、褪黑素、生物素、二巯基丁二钠、氨氯地平和艾司洛尔。
其中，所述药物颗粒或多丸的制备工艺，包括但不限于以下工艺的一种或几种：湿法制粒、干法制粒、挤出滚圆、熔融制粒、离子交换树脂制粒、小丸喷涂上药。
本发明的目的之二在于提供一种口服给药递送装置，其中包括目的之一所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置外接于所述第一开口的自由端，并使用于承载药物颗粒或多丸的空间与所述内腔相连通。
以下，对药物容置装置外设于所述第一开口的自由端的方式进行具体说明：
本方案中，较佳地，所述药物容置装置置于所述管状构件外，并通过固定套设方式或螺纹连接方式维持于所述管状构件的第一开口处。
本方案中，含活性药物成分的颗粒或多丸置于药物容置装置的腔体中，使用时，支撑部件的一端接触液体，通过啜吸作用将液体通过过滤部件吸入管状构件内，含活性药物成分的颗粒或多丸随液体进入管状构件内，进而进入口中。
本方案中，较佳地，所述第二开口处还设有一用于封口的顶盖，以保证口服给药递送装置在载药后，即使运输过程中发生颠簸或者完全倒置，药物颗粒或多丸也不会从第二开口处泄漏。进一步地，还可以使用独立的外包装将已载药的口服给药递送装置密封后，直接存储或运输，起到防水防潮的作用。
以下，对于管状构件的结构进行具体说明：
在本申请一较佳实施方式中，所述管状部件为一直吸管。所述直吸管上较佳地具有至少1个褶皱部结构。较佳地，所述褶皱部结构具有1对翼部和1个转折端；所述褶皱部结构可沿所述管状构件轴向拉伸或收缩，并在拉伸时形成湍流。
在本申请另一较佳实施方式中，所述管状部件具有至少2个管段，所述管段之间密封连接并可沿所述管状构件轴向拉伸或收缩；所述管状构件呈拉伸状态时形成具有至少1个台阶结构的湍流产生部件。
其中，当所述管段的数量为3个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的外径小于所述第一管段的内径，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段的内径、第二管段的外径、内径和第三管段的外径逐渐减小，且每一管段可沿 其他管段轴向拉伸或收缩。
其中，当所述管段的数量为4个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的内径与第四管段的内径相同，其中，所述第二管段的内径小于所述第一管段，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段至第四管段的内径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩。
本发明的目的之三在于提供一种口服给药递送装置，其中包括目的之一所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置设于所述内腔中、且靠近所述第一开口处，并使用于承载药物颗粒或多丸的空间与所述第二开口相连通；所述第一开口的直径小于所述药物容置装置的最小直径。
本方案中，通过限定第一开口的直径小于药物容置装置的最小直径，从而使得所述药物容置装置可以以任何方式维持于所述内腔中，而不会从所述管状构件的第一开口处脱落。
本方案中，较佳地，所述第二开口的直径小于所述药物容置装置的最小直径。
本方案中，较佳地，所述第二开口处还设有一用于封口的顶盖，以保证口服给药递送装置在载药后，即使运输过程中发生颠簸或者完全倒置，药物颗粒或多丸也不会从第二开口处泄漏。
本方案中，管状构件的结构的具体说明同目的之二部分所述。
本发明的目的之四在于提供一种固体口服制剂的药物容置装置，其结构为结构一或结构二：
结构一：所述的药物容置装置包括一过滤部件和用于支撑所述过滤部件的支撑部件，所述过滤部件和所述支撑部件相互配合形成用于承载药物颗粒或多丸的空间，所述过滤部件具有一个或多个允许液体通过的孔道；所述过滤部件上还设有一水溶性高分子材料层，从而使所述药物颗粒或多丸无法通过；
结构二：所述的药物容置装置为顶端开口、底部为筛网的筒状结构，所述筛网的内表面设有一水溶性高分子材料层，所述水溶性高分子材料层上方的筒状结构的内腔用于容纳药物颗粒或多丸。
本方案的适用范围广泛，尤其适用于所述药物颗粒或多丸的粒径分布中，部分粒径小于或等于所述孔道的孔径的情形。
以下，对结构一中过滤部件的结构、材质、孔径、制备工艺的设置条件进行具体说明：
本发明中，所述的过滤部件为本领域常规常见的类型，较佳地为一滤膜。所述滤膜较佳地为圆片状结构。所述滤膜的厚度较佳地为0.01～0.5mm，更佳地为0.1～0.3mm，例如0.2mm。在这种情况下，由于滤膜的厚度薄，功能类似筛网，当液体通过筛网的阻力很小时，粒径小于或等于滤膜孔径的药物颗粒或多丸会从所述过滤部件中泄漏出来，因此，在所述滤膜上设置一水溶性高分子材料层。
其中，所述的滤膜的材质为本领域常规的滤膜材质，包括但不限于以下材质中的一种或多种：聚丙烯、聚乙烯、聚氯乙烯、聚偏二氯乙烯、聚对苯二甲酸乙二酯、醋酸纤维素、聚乳酸、聚羟基乙酸、聚乳酸-羟基乙酸共聚物、玻璃纤维、尼龙、聚醚砜、聚偏氟乙烯和聚四氟乙烯。所述滤膜的原材料的形状包括但不限于颗粒状，片状，纤维状等。
其中，所述的滤膜中的孔道的形状和结构可为本领域常规的规则结构，例如以直线方式连接和贯通所述滤膜的上下表面。
其中，所述的滤膜的孔径大小为本领域常规，例如1-500μm，优选为20～400μm，更优选为40-300μm，例如150μm，200μm，250μm，300μm。
其中，所述的滤膜的直径可为本领域常规，滤膜的直径定义为发挥截留固体和通过液体的有效直径，出于设计和安装工艺的考虑，滤膜直径的最外圈会被上下支撑部件压在中间，用于固定滤膜，例如10mm直径的膜，边上1mm被支撑部件压边，有效直径只有8mm。滤膜常用的有效直径范围一般为4-20mm，较佳地为6-15mm，更佳地为8mm-12mm，例如为10mm。
其中，所述的滤膜的制备工艺为本领域常规工艺，包括但不限于烧结，注塑，压制，编织等。
以下，对所述水溶性高分子材料层的设置方式进行具体说明：
本发明中，所述水溶性高分子材料层的成型方式为本领域常规，较佳地为：在所述滤膜的上表面和/或下表面吸附、涂布或喷涂高分子材料溶液，或者将所述滤膜浸渍在高分子材料溶液中，干燥即可。干燥后，高分子材料分散在滤膜的膜孔和膜材中，形成具有一定硬度的骨架，同时堵住了滤膜的孔道，这样小于或等于滤膜孔径的药物颗粒或多丸在存储和运输过程中也不会泄漏。
具体的，所述水溶性高分子材料层形成的结构较佳地有如下两种：在滤膜的上表面或下表面形成一层连续的水溶性高分子材料层，或者高分子材料会完全堵塞滤膜的孔道、形成一个完整、致密的水溶性高分子材料层(例如通过使用浸渍方式形成这种结构)，更 佳地为仅在滤膜的上表面或下表面形成一层连续的水溶性高分子材料层(例如，通过仅在滤膜的某一表面吸附、涂布、或者喷涂的方式形成这种结构)，进一步更佳地为在滤膜的下表面形成一层连续的水溶性高分子材料层。
其中，所述的水溶性高分子材料层的溶解时间较佳地为小于等于10s，例如2s。在使用时，患者将药物容置装置置于液体中啜吸，与此同时水溶性高分子材料层在极短的时间内溶解，液体以极小的阻力通过药物容置装置，将药物颗粒或多丸递送入患者口中。由于水溶性高分子材料层溶解很快，患者使用时感觉不到阻力的变化。
其中，为了使高分子材料更好地成型在滤膜的表面，所述的水溶性高分子材料层较佳地选择具有较好的水溶性和成膜性而且分子量小的高分子材料，形成高分子材料溶液后，通过一定工艺成型制得。
其中，所述的高分子材料的分子量较佳地为2000-200000，更佳地为2000-100000。所述高分子材料的种类较佳地选自羟丙甲纤维素、共聚维酮、羟丙基纤维素、羟乙基纤维素(HEC)、聚维酮、聚乙二醇(PEG)、明胶、泊洛沙姆、黄原胶和尤特奇(Eudragit)中的一种或多种。
其中，所述高分子材料溶液的制备方法为本领域常规方法，具体包括如下步骤：将高分子材料与溶剂混合均匀即可。其中，所述溶剂为本领域常规的能溶解高分子材料、易挥发的溶剂，例如水，乙醇，丙酮等。
其中，所述水溶性高分子材料层的成型过程中，高分子材料溶液的粘度是成型过程中的关键参数，粘度取决于三个参数，聚合物的浓度、分子量和化学结构。粘度范围一般为2厘泊(cP)-5000厘泊(cP)，较佳地为2cP-1000cP。其中，所述高分子材料溶液的浓度较佳地为0.1％-30％，例如10％，所述浓度为质量百分比浓度。所述水溶性高分子材料层的成型过程中，高分子材料增重一般为0.01-60mg/cm2，较佳地为0.5-30mg/cm2，例如6.4mg/cm2。其中，“高分子材料增重”的含义是在每平方厘米的过滤部件(例如滤膜)或者筛网上形成的水溶性高分子材料层在固化干燥后的重量，重量单位以毫克计。
在本申请一较佳实施方式中，所述高分子材料溶液选择浓度为10％的羟丙甲纤维素E3溶液。
以下，对结构一中支撑部件的结构进行具体说明：
本发明中，所述支撑部件具有本领域常规含义，其作用在于能支撑所述过滤部件、但不影响所述过滤部件的过滤性和透液性。
在本申请一较佳实施方式中，所述支撑部件包括一上支撑部件、一下支撑部件，所述上支撑部件和所述下支撑部件可相互盖合、并将所述过滤部件夹持在中间，所述上支 撑部件与所述过滤部件的上方空间用于容纳药物颗粒或多丸。这种结构类似三明治形式。
在本申请另一较佳实施方式中，所述支撑部件包括一过滤部件容置部件和一药物容置部件，所述过滤部件容置部件和所述药物容置部件均具有一孔状结构端和一开放端，所述孔状结构端具有一个或多个允许液体通过的孔，所述过滤部件容置部件的开放端与所述药物容置部件的孔状结构端可盖合形成用于容纳所述过滤部件的腔体；所述药物容置部件的开放端为开口的管状结构，用于容纳药物颗粒或多丸。本领域技术人员均应理解，本实施方式中过滤部件容置部件的实际功能为与药物容置部件形成腔体，用于容纳过滤部件，这种结构也类似三明治形式。另外药物容置部件和过滤部件容置部件的孔状结构的尺寸不影响所述过滤部件的过滤性和透液性。
其中，所述支撑部件的材质为本领域常规材质，包括但不限于以下材质中的一种或多种：聚丙烯、聚乙烯、聚氯乙烯、聚偏二氯乙烯、聚偏氟乙烯、聚四氟乙烯、聚对苯二甲酸乙二酯、聚乳酸、聚羟基乙酸、聚乳酸-羟基乙酸共聚物、陶瓷、二氧化硅、有机硅。
其中，所述支撑部件的制备工艺为本领域常规，包括但不限于烧结，注塑成型等。
以下，对结构二中的筒状结构进行具体说明：
所述筒状结构的材质和制备工艺与支撑部件部分的描述相同。
所述筛网的尺寸为本领域常规，例如200μm。
以下，对药物颗粒或多丸的形态和种类进行具体说明：
本发明中，所述药物颗粒或多丸具有本领域常规含义，一般是指含有活性药物成分的颗粒、粉末或多丸。
其中，所述药物颗粒或多丸的粒径为本领域常规，一般为1-5000μm，优选为25-2000μm，更优选为50-1000μm。
较佳地，当所述药物颗粒或多丸的粒径范围为50-1000μm时，结构一中所述过滤部件或结构二中所述筛网的孔径为40-300μm。
其中，所述药物颗粒或多丸包含的活性药物成分为本领域常规，包括但不限于以下的一种或多种：达比加群酯或其药学上可接受的盐、阿哌沙班、利伐沙班、左旋多巴-卡比多巴、孟鲁司特、兰索拉唑、奥美拉唑、埃索美拉唑、阿莫西林、克拉霉素、阿奇霉素、甲硝唑、利福平、柳氮磺吡啶、对乙酰氨基酚、右美沙芬、多西拉敏、伪麻黄碱、苯海拉明、安非他命、哌甲酯、地拉罗司、ivacaftor、lumacaftor、他克莫司、地西泮、氯巴占、氨己烯酸、波生坦、褪黑素、生物素、二巯基丁二钠、氨氯地平和艾司洛尔。
其中，所述药物颗粒或多丸的制备工艺，包括但不限于以下工艺的一种或几种：湿 法制粒、干法制粒、挤出滚圆、熔融制粒、离子交换树脂制粒、小丸喷涂上药。
本发明的目的之五在于提供一种口服给药递送装置，其中包括目的之四所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置外接于所述第一开口的自由端，并使用于承载药物颗粒或多丸的空间与所述内腔相连通。
以下，对药物容置装置外设于所述第一开口的自由端的方式进行具体说明：
本发明中，所述药物容置装置置于所述管状构件外，较佳地通过固定套设方式或螺纹连接方式维持于所述管状构件外的第一开口处。
本实施方式中，含活性药物成分的颗粒或多丸置于药物容置装置的腔体中，使用时，支撑部件的一端接触液体，通过啜吸作用将液体通过过滤部件吸入管状构件内，含活性药物成分的颗粒或多丸随液体进入管状构件内，进而进入口中。
本发明中，较佳地，所述第二开口处还设有一用于封口的顶盖，以保证口服给药递送装置在载药后，即使运输过程中发生颠簸或者完全倒置，药物颗粒或多丸也不会从第二开口处泄漏。
以下，对于管状构件的结构进行具体说明：
在本申请一较佳实施方式中，所述管状部件为一直吸管。所述直吸管上较佳地具有至少1个褶皱部结构。较佳地，所述褶皱部结构具有1对翼部和1个转折端；所述褶皱部结构可沿所述管状构件轴向拉伸或收缩，并在拉伸时形成湍流。
在本申请另一较佳实施方式中，所述管状部件具有至少2个管段，所述管段之间密封连接并可沿所述管状构件轴向拉伸或收缩；所述管状构件呈拉伸状态时形成具有至少1个台阶结构的湍流产生部件。
其中，当所述管段的数量为3个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的外径小于所述第一管段的内径，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段的内径、第二管段的外径、内径和第三管段的外径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩。
其中，当所述管段的数量为4个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的内径与第四管段的内径相同，其中，所述第二管段的内径小于所述第一管段，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段至第四管段的内径逐渐减小，且每 一管段可沿其他管段轴向拉伸或收缩。
本发明的目的之六在于提供一种口服给药递送装置，其中包括目的之四所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置设于所述内腔中、且靠近所述第一开口处，并使用于承载药物颗粒或多丸的空间与所述第二开口相连通；所述第一开口的直径小于所述药物容置装置的最小直径。
本发明中，通过限定第一开口的直径小于药物容置装置的最小直径，从而使得所述药物容置装置可以以任何方式维持于所述内腔中，而不会从所述管状构件的第一开口处脱落。
本发明中，较佳地，所述第二开口的直径小于所述药物容置装置的最小直径。
本发明中，较佳地，所述第二开口处还设有一用于封口的顶盖，以保证口服给药递送装置在载药后，即使运输过程中发生颠簸或者完全倒置，药物颗粒或多丸也不会从第二开口处泄漏。
本发明中，管状构件的结构的具体说明同目的之五部分所述。
本发明的目的之七在于提供一种固体口服制剂的药物容置装置，其包括一过滤部件和用于支撑所述过滤部件的支撑部件，所述过滤部件和所述支撑部件相互配合形成用于承载药物颗粒或多丸的空间，所述过滤部件具有一个或多个允许液体通过的孔道；所述孔道在所述过滤部件的内部以上下错综交叉的方式分布，所述过滤部件上还设有一水溶性高分子材料层，从而使所述药物颗粒或多丸无法通过。
本方案的适用范围广泛，尤其适用于所述药物颗粒或多丸的粒径分布中，部分粒径小于或等于所述孔道的孔径的情形。
本方案的机理在于：由于药物颗粒或多丸的粒径分布是一个范围，由于工艺的限制，不可能将小于一定粒径的颗粒或多丸全部消除，这种情况下，为了保证啜吸时较小的阻力，设置上下错综交叉的孔道结构时会选择相对较大的孔径，为了满足不泄漏的需求，因此，需要在将过滤部件(例如滤膜)设置为上下错综交叉的孔道结构的同时，在所述滤膜上设置一水溶性高分子材料层。
以下，对所述过滤部件的结构、材质、孔径、制备工艺的设置条件进行具体说明：
本发明中，所述的过滤部件为本领域常规常见的类型，较佳地为一滤膜。所述滤膜较佳地为圆柱状结构。所述滤膜的厚度较佳地为0.3～20mm，更佳地为0.5～15mm，进一步更佳地为0.5～10mm，例如2mm。
也就是说，滤膜具有一定的厚度，因此将滤膜的孔道设置为上下错综交叉的结构，优选是将滤膜的上下表面以及内部的孔道都设置为不规则的、且错综交叉的结构，例如海绵状的多孔结构，或者由多层纤维无规则层叠排列、压制而成的蓬松结构。
其中，所述的滤膜的材质为本领域常规的滤膜材质，包括但不限于以下材质中的一种或多种：聚丙烯、聚乙烯、聚氯乙烯、聚偏二氯乙烯、聚对苯二甲酸乙二酯、醋酸纤维素、聚乳酸、聚羟基乙酸、聚乳酸-羟基乙酸共聚物、玻璃纤维、尼龙、聚醚砜、聚偏氟乙烯和聚四氟乙烯。所述滤膜的原材料的形状包括但不限于颗粒状，片状，纤维状等。
其中，所述的滤膜中的孔道的形状和结构可为本领域常规的规则结构，例如以直线方式连接和贯通所述滤膜的上下表面。
其中，所述的滤膜的孔径大小为本领域常规，例如1-500μm，优选为20～400μm，更优选为40-300μm，例如150μm，200μm，250μm，300μm。
其中，所述的滤膜的直径可为本领域常规，滤膜的直径定义为发挥截留固体和通过液体的有效直径，出于设计和安装工艺的考虑，滤膜直径的最外圈会被上下支撑部件压在中间，用于固定滤膜，例如10mm直径的膜，边上1mm被支撑部件压边，有效直径只有8mm。滤膜常用的有效直径范围一般为4-20mm，较佳地为6-15mm，更佳地为8mm-12mm，例如为10mm。
其中，所述的滤膜的制备工艺为本领域常规工艺，包括但不限于烧结，注塑，压制，编织等。
以下，对所述水溶性高分子材料层的设置方式进行具体说明：
本发明中，所述水溶性高分子材料层的成型方式为本领域常规，较佳地为：在所述滤膜的上表面和/或下表面吸附、涂布或喷涂高分子材料溶液，或者将所述滤膜浸渍在高分子材料溶液中，干燥即可。干燥后，高分子材料分散在滤膜的膜孔和膜材中，形成具有一定硬度的骨架，同时堵住了滤膜的孔道，这样小于或等于滤膜孔径的药物颗粒或多丸在存储和运输过程中也不会泄漏。
具体的，所述水溶性高分子材料层形成的结构较佳地有如下两种：在滤膜的上表面或下表面形成一层连续的水溶性高分子材料层，或者高分子材料会完全堵塞滤膜的孔道、形成一个完整、致密的水溶性高分子材料层(例如通过使用浸渍方式形成这种结构)，更佳地为仅在滤膜的上表面或下表面形成一层连续的水溶性高分子材料层(例如，通过仅在滤膜的某一表面吸附、涂布、或者喷涂的方式形成这种结构)，进一步更佳地为在滤膜的下表面形成一层连续的水溶性高分子材料层。
其中，所述的水溶性高分子材料层的溶解时间较佳地为小于等于10s，例如2s。在 使用时，患者将药物容置装置置于液体中啜吸，与此同时水溶性高分子材料层在极短的时间内溶解，液体以极小的阻力通过药物容置装置，将药物颗粒递送入患者口中。由于水溶性高分子材料层溶解很快，患者使用时感觉不到阻力的变化。
其中，为了使高分子材料溶液更好地成型在滤膜的表面，较佳地选择具有较好的水溶性和成膜性而且分子量小的高分子材料溶液。其中，所述的高分子材料的分子量一般为2000-200000，较佳地为2000-100000。更佳地，所述高分子材料的种类选自羟丙甲纤维素(HPMC)、共聚维酮、羟丙基纤维素(HPC)、羟乙基纤维素(HEC)、聚维酮、聚乙二醇(PEG)、明胶、泊洛沙姆、黄原胶和尤特奇(Eudragit)中的一种或多种。
其中，所述高分子材料溶液的制备方法为本领域常规方法，具体包括如下步骤：将高分子材料与溶剂混合均匀即可。其中，所述溶剂为本领域常规的能溶解高分子材料、易挥发的溶剂，例如水，乙醇，丙酮等。
其中，所述水溶性高分子材料层的成型过程中，高分子材料溶液的粘度是成型过程中的关键参数，粘度取决于三个参数，聚合物的浓度、分子量和化学结构。粘度范围一般为2厘泊(cP)-5000厘泊(cP)，较佳地为2cP-1000cP。其中，所述高分子材料溶液的浓度较佳地为0.1％-30％，例如10％，所述浓度为质量百分比浓度。高分子材料增重一般为0.01-60mg/cm2，较佳地为0.5-30mg/cm2，例如6.4mg/cm2。
在本申请一较佳实施方式中，所述高分子材料溶液选择浓度为10％的羟丙甲纤维素E3溶液。
以下，对支撑部件的结构进行具体说明：
本发明中，所述支撑部件具有本领域常规含义，其作用在于能支撑所述过滤部件、但不影响所述过滤部件的过滤性和透液性。
在本申请一较佳实施方式中，所述支撑部件包括一上支撑部件、一下支撑部件，所述上支撑部件和所述下支撑部件可相互盖合、并将所述过滤部件夹持在中间，所述上支撑部件与所述过滤部件的上方空间用于容纳药物颗粒或多丸。这种结构类似三明治形式。
在本申请另一较佳实施方式中，所述支撑部件包括一过滤部件容置部件和一药物容置部件，所述过滤部件容置部件和所述药物容置部件均具有一孔状结构端和一开放端，所述孔状结构端具有一个或多个允许液体通过的孔，所述过滤部件容置部件的开放端与所述药物容置部件的孔状结构端可盖合形成用于容纳所述过滤部件的腔体；所述药物容置部件的开放端为开口的管状结构，用于容纳药物颗粒或多丸。本领域技术人员均应理解，本实施方式中过滤部件容置部件的实际功能为与药物容置部件形成腔体，用于容纳过滤部件，这种结构也类似三明治形式。另外药物容置部件和过滤部件容置部件的孔状 结构的尺寸不影响所述过滤部件的过滤性和透液性。
其中，所述支撑部件的材质为本领域常规材质，包括但不限于以下材质中的一种或多种：聚丙烯、聚乙烯、聚氯乙烯、聚偏二氯乙烯、聚偏氟乙烯、聚四氟乙烯、聚对苯二甲酸乙二酯、聚乳酸、聚羟基乙酸、聚乳酸-羟基乙酸共聚物、陶瓷、二氧化硅、有机硅。
其中，所述支撑部件的制备工艺为本领域常规，包括但不限于烧结，注塑成型等。
以下，对药物颗粒或多丸的形态和种类进行具体说明：
本发明中，所述药物颗粒或多丸具有本领域常规含义，一般是指含有活性药物成分的颗粒、粉末或多丸。
其中，所述药物颗粒或多丸的粒径为本领域常规，一般为1-5000μm，优选为25-2000μm，更优选为50-1000μm。
较佳地，当所述药物颗粒或多丸的粒径范围为50-1000μm时，所述过滤部件的孔径为40-300μm。
其中，所述药物颗粒或多丸包含的活性药物成分为本领域常规，包括但不限于以下的一种或多种：达比加群酯或其药学上可接受的盐、阿哌沙班、利伐沙班、左旋多巴-卡比多巴、孟鲁司特、兰索拉唑、奥美拉唑、埃索美拉唑、阿莫西林、克拉霉素、阿奇霉素、甲硝唑、利福平、柳氮磺吡啶、对乙酰氨基酚、右美沙芬、多西拉敏、伪麻黄碱、苯海拉明、安非他命、哌甲酯、地拉罗司、ivacaftor、lumacaftor、他克莫司、地西泮、氯巴占、氨己烯酸、波生坦、褪黑素、生物素、二巯基丁二钠、氨氯地平和艾司洛尔。
其中，所述药物颗粒或多丸的制备工艺，包括但不限于以下工艺的一种或几种：湿法制粒、干法制粒、挤出滚圆、熔融制粒、离子交换树脂制粒、小丸喷涂上药。
本发明的目的之八在于提供一种口服给药递送装置，其中包括目的之七所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置外接于所述第一开口的自由端，并使用于承载药物颗粒或多丸的空间与所述内腔相连通。
以下，对药物容置装置外设于所述第一开口的自由端的方式进行具体说明：
本发明中，所述药物容置装置置于所述管状构件外，较佳地通过固定套设方式或螺纹连接的方式维持于所述管状构件外的第一开口处。
本实施方式中，含活性药物成分的颗粒或多丸置于药物容置装置的腔体中，使用时，支撑部件的一端接触液体，通过啜吸作用将液体通过过滤部件吸入管状构件内，含活性 药物成分的颗粒或多丸随液体进入管状构件内，进而进入口中。
本发明中，较佳地，所述第二开口处还设有一用于封口的顶盖，以保证口服给药递送装置在载药后，即使运输过程中发生颠簸或者完全倒置，药物颗粒或多丸也不会从第二开口处泄漏。
以下，对于管状构件的结构进行具体说明：
在本申请一较佳实施方式中，所述管状部件为一直吸管。所述直吸管上较佳地具有至少1个褶皱部结构。较佳地，所述褶皱部结构具有1对翼部和1个转折端；所述褶皱部结构可沿所述管状构件轴向拉伸或收缩，并在拉伸时形成湍流。
在本申请另一较佳实施方式中，所述管状部件具有至少2个管段，所述管段之间密封连接并可沿所述管状构件轴向拉伸或收缩；所述管状构件呈拉伸状态时形成具有至少1个台阶结构的湍流产生部件。
其中，当所述管段的数量为3个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的外径小于所述第一管段的内径，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段的内径、第二管段的外径、内径和第三管段的外径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩。
其中，当所述管段的数量为4个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的内径与第四管段的内径相同，其中，所述第二管段的内径小于所述第一管段，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段至第四管段的内径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩。
本发明的目的之九在于提供一种口服给药递送装置，其中包括目的之七所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置设于所述内腔中、且靠近所述第一开口处，并使用于承载药物颗粒或多丸的空间与所述第二开口相连通；所述第一开口的直径小于所述药物容置装置的最小直径。
本发明中，通过限定第一开口的直径小于药物容置装置的最小直径，从而使得所述药物容置装置可以以任何方式维持于所述内腔中，而不会从所述管状构件的第一开口处脱落。
本发明中，较佳地，所述第二开口的直径小于所述药物容置装置的最小直径。
本发明中，较佳地，所述第二开口处还设有一用于封口的顶盖，以保证口服给药递送装置在载药后，即使运输过程中发生颠簸或者完全倒置，药物颗粒或多丸也不会从第二开口处泄漏。
本发明中，管状构件的结构的具体说明同目的之八部分所述。
本领域技术人员均应理解，本发明中，对于“第一开口”、“第二开口”、“第一管段”、“第二管段”、“第三管段”、“第四管段”等的描述，是为了便于说明，不应理解为对特定的位置或顺序的限定。
在符合本领域常识的基础上，上述各优选条件，可任意组合，即得本发明各较佳实例。本发明所用试剂和原料均市售可得。
本发明的积极进步效果在于：本发明的药物容置装置可以较好地解决药物颗粒泄漏和啜吸时流体阻力大的问题，配合管状构件后形成的口服给药递送装置可作为直接接触药物的药包材使用，具有存储功能。本发明的所述口服给药递送装置在使用时，经检测，当吸管长度为20cm时，充满吸管的液体仅在重力作用下排空的时间小于12s。
附图说明
图1是实施例1的药物容置装置中支撑部件和过滤部件的结构示意图，1a为下支撑部件，1b是过滤部件，1c是上支撑部件；
图2是实施例1的药物容置装置中支撑部件和过滤部件的组装示意图，2a为组装前，2b是组装后；
图3是实施例1的药物容置装置与吸管组装后形成内置式口服给药递送装置的结构示意图；
图4是实施例2的药物容置装置的支撑部件和过滤部件的结构示意图，4a为笼状支撑部件，4b是过滤部件，4c是笼状支撑部件的上盖；
图5是实施例2的药物容置装置的支撑部件和过滤部件的组装示意图；
图6是实施例2的药物容置装置与吸管组装后形成内置式口服给药递送装置的示意图；
图7是实施例1～3的内置式口服给药递送装置在吸管使用时的示意图，7a为啜吸前，7b是啜吸后；
图8是实施例4的药物容置装置中过滤部件容置部件、过滤部件和药物容置部件的结构示意图，8a为过滤部件容置部件，8b是过滤部件，8c是药物容置部件；
图9是实施例4的药物容置装置中过滤部件容置部件、过滤部件和药物容置部件的 组装示意图，9a为组装前，9b是组装后；
图10是实施例4的药物容置装置与吸管组装后形成外置式口服给药递送装置的示意图；
图11是实施例4的外置式口服给药递送装置在吸管使用时的示意图，11a为啜吸前，11b是啜吸后；
图12为实施例中过滤部件的内部孔道为不规则、错综交叉结构的剖视图；
图13为实施例8的药物容置装置的结构示意图；
图14为实施例8的口服给药递送装置的结构示意图。
具体实施方式
实施例1(水溶性高分子材料层+内置)
如图1～3所示，将孔径为150μm、厚度为0.2mm、材质为聚丙烯的滤膜，剪裁为直径为1cm的圆片。将上述滤膜置于10％羟丙甲纤维素E3溶液中浸润，然后置于烘箱中干燥。干燥后(增重为6.4mg/cm 2)，将其置于直径为1cm，厚度为3mm的两个聚乙烯圆片之间，两个聚乙烯圆片上布满2mm×2mm上下通透的网格。其中一个聚乙烯圆片表面具有四个直径为2mm的凸起，另一个聚乙烯圆片表面的对称位置为四个直径为2mm的凹坑，两个圆片通过凹凸结构的机械缩合，将滤膜紧紧的固定在中间，组成药物容置装置。将此装置从接触液体一端的管口，置于内径为1.05cm的带有褶皱的吸管中，将管口内拗，药物容置装置便可以滞留在吸管中。
实施例2(错综交叉孔道结构+内置)
如图4～6所示，将孔径为300μm、厚度为6mm、材质为聚丙烯的滤膜，(滤膜设置了错综交叉的不规则孔道)(图12是图4和图8中过滤部件的内部孔道结构示意图)，切割为直径为8mm的圆柱。将上述圆柱状滤膜置于内腔直径为8.1mm、高6mm的圆筒状的滤膜容置装置中；筒底和筒盖上布满2mm×2mm上下通透的网格；筒盖通过机械缩合与筒身固定，将滤膜包裹其中，组成药物容置装置。将此装置从接触液体一端的管口，置于内径为1.2cm的带有褶皱的吸管中，将管口内拗，药物容置装置便可以滞留在吸管中。
实施例3(错综交叉孔道结构+水溶性高分子材料层+内置)
如图1～3所示，将孔径为300μm、厚度为1.5mm、材质为聚丙烯的滤膜(滤膜设置了错综交叉的不规则孔道)，剪裁为直径为1cm的圆片。将上述滤膜置于10％羟丙甲纤维素E3溶液中浸润，然后置于烘箱中干燥。干燥后(增重为25.5mg/cm 2)，将其置于直 径为1cm，厚度为3mm的两个聚乙烯圆片之间，两个聚乙烯圆片上布满2mm×2mm上下通透的网格。其中一个聚乙烯圆片表面具有四个直径为2mm的凸起，另一个聚乙烯圆片表面的对称位置为四个直径为2mm的凹坑，两个圆片通过凹凸结构的机械缩合，将滤膜紧紧的固定在中间，组成药物容置装置。将此装置从接触液体一端的管口，置于内径为1.05cm的带有褶皱的吸管中，将管口内拗，药物容置装置便可以滞留在吸管中。
实施例1、2和3的装置在使用时的结构示意图如图7所示。
实施例4(错综交叉孔道结构+外置)
如图8～11所示，将孔径为100μm、厚度为2mm、材质为聚丙烯的滤膜(滤膜设置了错综交叉的不规则孔道)，剪裁为直径为12mm的圆片。采用注塑成型的工艺，制备过滤部件的容置部件和药物容置部件。上述过滤部件容置部件为内径为12.1mm、内部高度为4mm的圆筒状结构，筒底具有直径8mm上下通透的圆孔；上述药物容置部件为内径为9.1mm、内部高度为1.5cm的圆筒状结构。将滤膜置于过滤部件容置部件的筒状结构中，然后将药物容置部件的下端压在上面，两者通过机械结构缩合，将滤膜固定在中间，得到药物容置装置。然后将药物容置装置的上端与带有褶皱吸管(内径8.6mm)的接触液体一端的管口连接。将504.1mg热熔制粒的甲磺酸达比加群酯颗粒(含75mg达比加群酯，粒径分布见表1)通过吸管上端填充至上述药物容置装置中，没有颗粒通过药物容置装置泄漏。使用时，将吸管带有药物容置装置的一端置于液体中，患者通过啜吸，将液体吸入吸管内，液体轻松的通过药物容置装置并推动着甲磺酸达比加群酯颗粒进入患者口中，完成用药。
表1热熔制粒的甲磺酸达比加群酯颗粒粒径分布
粒径范围 百分比
＞355μm 23.8％
250-355μm 7.6％
180-250μm 35.9％
180μm 32.7％
实施例5(错综交叉孔道结构+水溶性高分子材料层+外置)
如图8～11所示，通将孔径为300μm、厚度为1.5mm、材质为聚丙烯的滤膜，滤膜设置了错综交叉的不规则孔道，剪裁为直径为12mm的圆片。将上述滤膜置于10％KillidonVA64(共聚维酮)乙醇溶液中浸润，然后置于烘箱中干燥，干燥后增重为16.0mg/cm 2。采用注塑成型的工艺，制备过滤部件的容置部件和药物容置部件。上述过滤部件容置部件为内径为12.1mm、内部高度为4mm的圆筒状结构，筒底具有直径8mm上下通透的圆 孔；上述药物容置部件为内径为9.1mm、内部高度为1.5cm的圆筒状结构。将滤膜置于过滤部件容置部件的筒状结构中，然后将药物容置部件的下端压在上面，两者通过机械结构缩合，将滤膜固定在中间，得到药物容置装置。然后将药物容置装置的上端与带有褶皱吸管(内径8.6mm)的接触液体一端的管口连接。将500mg粒径范围为75μm-150μm的D-甘露醇丸芯通过吸管上端填充至上述药物容置装置的圆筒中，没有小丸通过药物容置装置泄漏。
实施例6(水溶性高分子材料层+外置)
如图8～11所示，将孔径为250μm、厚度为0.3mm、材质为聚丙烯的滤膜，剪裁为直径为12mm的圆片。将上述滤膜置于10％Killidon VA64(共聚维酮)乙醇溶液中浸润，然后置于烘箱中干燥，干燥后增重为8.9mg/cm 2。采用注塑成型的工艺，制备过滤部件的容置部件和药物容置部件。上述过滤部件容置部件为内径为12.1mm、内部高度为3mm的圆筒状结构，筒底具有直径8mm上下通透的圆孔；上述药物容置部件为内径为9.1mm、内部高度为1.5cm的圆筒状结构。将滤膜置于过滤部件容置部件的筒状结构中，然后将药物容置部件的下端压在上面，两者通过机械结构缩合，将滤膜固定在中间，得到药物容置装置。然后将药物容置装置的上端与带有褶皱吸管(内径8.6mm)的接触液体一端的管口连接。
实施例7(错综交叉孔道结构+外置)
将实施例4中的药物容置装置，与总长为20cm、内径8.6mm、褶皱长度为4cm的吸管装配。将药物容置装置的下端用手指堵上，从上端将吸管充满液体，在重力作用下，装置中液体的排空时间约为2秒-3秒。
实施例8(水溶性高分子材料层+外置)
如图13～14所示，采用注塑成型工艺，制备药物容置装置。上述药物容置装置为内径为9mm、高度为2cm、壁厚1mm的圆筒状结构；筒底内径9mm，具多个上下通透孔径为200μm的筛网；筒口内壁设计有两圈凸起的环状结构，用于以外接方式连接吸管。将7.5％HPMC E3水溶液涂布至筒底内表面并干燥，增重为17.7mg/cm 2，得到药物容置装置。
实施例9(错综交叉孔道结构+外置)
如图8～11所示，将孔径为100μm、厚度为2mm、材质为聚丙烯的滤膜(滤膜设置了错综交叉的不规则孔道)，剪裁为直径为16mm的圆片。采用注塑成型的工艺，制备过滤部件的容置部件和药物容置部件。上述过滤部件容置部件为内径为16.1mm、内部高度为4mm的圆筒状结构，筒底具有直径12mm上下通透的圆孔；上述药物容置部件为内径 为12.5mm、内部高度为1.5cm的圆筒状结构。将滤膜置于过滤部件容置部件的筒状结构中，然后将药物容置部件的下端压在上面，两者通过机械结构缩合，将滤膜固定在中间，得到药物容置装置。然后将药物容置装置的上端与带有褶皱吸管(内径12mm)的接触液体一端的管口连接。将320mg奥美拉唑肠溶多丸(含20mg奥美拉唑)、1334mg阿莫西林颗粒(含1000mg阿莫西林)和840mg克拉霉素颗粒(含500mg克拉霉素)通过吸管上端填充至药物容置装置中，没有多丸或颗粒通过药物容置装置泄漏。使用时，将吸管带有药物容置装置的一端置于液体中，患者通过啜吸，将液体吸入吸管内，液体轻松的通过药物容置装置并推动着上述多丸进入患者口中，完成用药。其中奥美拉唑肠溶多丸的粒径范围是0.25-0.355mm。阿莫西林颗粒和克拉霉素颗粒的粒径分布见表2和表3。
表2阿莫西林颗粒粒径分布
粒径范围 百分比
425-600μm 22.8％
250-425μm 33.6％
150-250μm 25.7％
＜15Oμm 17.9％
表3克拉霉素颗粒粒径分布
粒径范围 百分比
425-600μm 32.1％
250-425μm 16.7％
150-250μm 28.9％
＜15Oμm 22.3％
实施例10(错综交叉孔道结构+内置)
本实施例与实施例2的结构和其他参数均相同，得到的防泄漏效果也相同，不同之处仅在于将实施例2中的滤膜替换为海绵状的多孔结构，从而使其具有不规则的、且错综交叉的结构。
实施例11(错综交叉孔道结构+外置)
本实施例与实施例4的结构和其他参数均相同，得到的防泄漏效果也相同，不同之处仅在于将实施例4中的滤膜替换为多层纤维无规则层叠排列、压制而成的蓬松结构，从而使其具有不规则的、且错综交叉的结构。
虽然以上描述了本发明的具体实施方式，但是本领域的技术人员应当理解，这些仅是举例说明，在不背离本发明的原理和实质的前提下，可以对这些实施方式做出多种变 更或修改。因此，本发明的保护范围由所附权利要求书限定。

Claims (23)

  1. 一种固体口服制剂的药物容置装置，其特征在于，其包括一过滤部件和用于支撑所述过滤部件的支撑部件，所述过滤部件和所述支撑部件相互配合形成用于承载药物颗粒或多丸的空间，所述过滤部件具有一个或多个允许液体通过的孔道；所述过滤部件的厚度为0.5mm以上，所述孔道在所述过滤部件的内部以上下错综交叉的方式分布，从而使所述药物颗粒或多丸无法通过。
  2. 如权利要求1所述的药物容置装置，其特征在于，所述的过滤部件为滤膜；
    所述滤膜的形状较佳地为圆柱状结构；
    所述滤膜的厚度较佳地为0.5～20mm，更佳地为0.5～15mm，进一步更佳地为0.5～10mm；
    较佳地，将所述滤膜的上下表面以及内部的孔道都设置为不规则的、且错综交叉的结构，更佳地为海绵状的多孔结构，或者由多层纤维无规则层叠排列、压制而成的蓬松结构；
    所述的滤膜的孔径较佳地为1-500μm，更佳地为20～400μm，进一步更佳地为40-300μm；
    所述的滤膜的有效直径较佳地为4-20mm，更佳地为6-15mm，进一步更佳地为8mm-12mm；
    和/或，
    所述药物颗粒或多丸的粒径为1-5000μm，较佳地为25-2000μm，更佳地为50-1000μm；
    较佳地，当所述药物颗粒或多丸的粒径范围为50-1000μm时，所述过滤部件的孔径为40-300μm；
    和/或，
    所述药物颗粒或多丸包含的活性药物成分包括但不限于以下的一种或多种：达比加群酯或其药学上可接受的盐、阿哌沙班、利伐沙班、左旋多巴-卡比多巴、孟鲁司特、兰索拉唑、奥美拉唑、埃索美拉唑、阿莫西林、克拉霉素、阿奇霉素、甲硝唑、利福平、柳氮磺吡啶、对乙酰氨基酚、右美沙芬、多西拉敏、伪麻黄碱、苯海拉明、安非他命、哌甲酯、地拉罗司、ivacaftor、lumacaftor、他克莫司、地西泮、氯巴占、氨己烯酸、波生坦、褪黑素、生物素、二巯基丁二钠、氨氯地平和艾司洛尔。
  3. 如权利要求1-2中至少一项所述的药物容置装置，其特征在于，所述支撑部件的结构为：设置在所述过滤部件的上下表面、将所述过滤部件夹持在中间；或以笼状结构 将所述过滤部件包裹在内部；
    较佳地，所述支撑部件的结构为如下结构中的任意一种：
    所述支撑部件包括一上支撑部件、一下支撑部件，所述上支撑部件和所述下支撑部件可相互盖合、并将所述过滤部件夹持在中间，所述上支撑部件与所述过滤部件的上方空间用于容纳药物颗粒或多丸；
    或者，所述支撑部件包括一过滤部件容置部件和一药物容置部件，所述过滤部件容置部件和所述药物容置部件均具有一孔状结构端和一开放端，所述孔状结构端具有一个或多个允许液体通过的孔，所述过滤部件容置部件的开放端与所述药物容置部件的孔状结构端可盖合形成用于容纳所述过滤部件的腔体；所述药物容置部件的开放端为开口的管状结构，用于容纳药物颗粒或多丸；
    或者，所述支撑部件包括一开口向上的笼状支撑部件和一与所述笼状支撑部件配合的上盖，所述上盖上开有供药物颗粒或多丸以及液体流通的孔道，所述笼状支撑部件和所述上盖可围合形成一个中空空间、并将所述过滤部件限制在该空间中，所述上盖与所述过滤部件的上方空间用于容纳药物颗粒或多丸。
  4. 一种口服给药递送装置，其特征在于，其包括如权利要求1～3至少一项所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置外接于所述第一开口的自由端，并使用于承载药物颗粒或多丸的空间与所述内腔相连通。
  5. 如权利要求4所述的口服给药递送装置，其特征在于，所述药物容置装置置于所述管状构件外，并通过固定套设方式或螺纹连接方式维持于所述管状构件的第一开口处；
    和/或，所述第二开口处还设有一用于封口的顶盖；
    和/或，所述管状部件为一直吸管；所述直吸管上较佳地具有至少1个褶皱部结构；较佳地，所述褶皱部结构具有1对翼部和1个转折端，所述褶皱部结构可沿所述管状构件轴向拉伸或收缩，并在拉伸时形成湍流；
    和/或，所述管状部件具有至少2个管段，所述管段之间密封连接并可沿所述管状构件轴向拉伸或收缩；所述管状构件呈拉伸状态时形成具有至少1个台阶结构的湍流产生部件；
    其中，当所述管段的数量为3个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的外径小于所述第一管段的内径，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的 第一管段的内径、第二管段的外径、内径和第三管段的外径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩；
    其中，当所述管段的数量为4个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的内径与第四管段的内径相同，其中，所述第二管段的内径小于所述第一管段，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段至第四管段的内径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩。
  6. 一种口服给药递送装置，其特征在于，其包括如权利要求1～3至少一项所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置设于所述内腔中、且靠近所述第一开口处，并使用于承载药物颗粒或多丸的空间与所述第二开口相连通；所述第一开口的直径小于所述药物容置装置的最小直径。
  7. 如权利要求6所述的口服给药递送装置，其特征在于，所述第二开口的直径小于所述药物容置装置的最小直径；
    和/或，所述第二开口处还设有一用于封口的顶盖；
    和/或，所述管状构件的结构如权利要求5所述。
  8. 一种固体口服制剂的药物容置装置，其特征在于，其结构为结构一或结构二：
    结构一：所述的药物容置装置包括一过滤部件和用于支撑所述过滤部件的支撑部件，所述过滤部件和所述支撑部件相互配合形成用于承载药物颗粒或多丸的空间，所述过滤部件具有一个或多个允许液体通过的孔道；所述过滤部件上还设有一水溶性高分子材料层，从而使所述药物颗粒或多丸无法通过；
    结构二：所述的药物容置装置为顶端开口、底部为筛网的筒状结构，所述筛网的内表面设有一水溶性高分子材料层，所述水溶性高分子材料层上方的筒状结构的内腔用于容纳药物颗粒或多丸。
  9. 如权利要求8所述的药物容置装置，其特征在于，所述的过滤部件为滤膜；
    所述滤膜的形状较佳地为圆片状结构；
    所述滤膜的厚度较佳地为0.01～0.5mm，更佳地为0.1～0.3mm；
    较佳地，将所述滤膜中的孔道以直线方式连接和贯通所述滤膜的上下表面；
    所述的滤膜的孔径较佳地为1-500μm，更佳地为20～400μm，进一步更佳地为40-300μm；
    所述的滤膜的有效直径较佳地为4-20mm，更佳地为6-15mm，进一步更佳地为8mm-12mm；
    和/或，
    所述药物颗粒或多丸的粒径为1-5000μm，较佳地为25-2000μm，更佳地为50-1000μm；
    较佳地，当所述药物颗粒或多丸的粒径范围为50-1000μm时，结构一中所述过滤部件或结构二中所述筛网的孔径为40-300μm；
    和/或，
    所述药物颗粒或多丸包含的活性药物成分包括但不限于以下的一种或多种：达比加群酯或其药学上可接受的盐、阿哌沙班、利伐沙班、左旋多巴-卡比多巴、孟鲁司特、兰索拉唑、奥美拉唑、埃索美拉唑、阿莫西林、克拉霉素、阿奇霉素、甲硝唑、利福平、柳氮磺吡啶、对乙酰氨基酚、右美沙芬、多西拉敏、伪麻黄碱、苯海拉明、安非他命、哌甲酯、地拉罗司、ivacaftor、lumacaftor、他克莫司、地西泮、氯巴占、氨己烯酸、波生坦、褪黑素、生物素、二巯基丁二钠、氨氯地平和艾司洛尔。
  10. 如权利要求8-9中至少一项所述的药物容置装置，其特征在于，所述水溶性高分子材料层形成的结构为如下两种：在所述的滤膜的上表面或下表面形成一层连续的水溶性高分子材料层，或者完全堵塞所述的滤膜的孔道、形成一个完整、致密的水溶性高分子材料层；
    和/或，所述的水溶性高分子材料层的溶解时间为小于等于10s；
    和/或，所述的水溶性高分子材料层中高分子材料的分子量为2000-200000，较佳地为2000-100000；
    和/或，所述的水溶性高分子材料层中所述高分子材料的种类选自羟丙甲纤维素、共聚维酮、羟丙基纤维素、羟乙基纤维素、聚维酮、聚乙二醇、明胶、泊洛沙姆、黄原胶和尤特奇中的一种或多种；
    和/或，所述水溶性高分子材料层的成型过程中，高分子材料增重为0.01-60mg/cm 2，较佳地为0.5-30mg/cm 2。
  11. 如权利要求8-10中至少一项所述的药物容置装置，其特征在于，所述支撑部件的结构为如下结构中的任意一种：
    所述支撑部件包括一上支撑部件、一下支撑部件，所述上支撑部件和所述下支撑部件可相互盖合、并将所述过滤部件夹持在中间，所述上支撑部件与所述过滤部件的上方空间用于容纳药物颗粒或多丸；
    或者，所述支撑部件包括一过滤部件容置部件和一药物容置部件，所述过滤部件容 置部件和所述药物容置部件均具有一孔状结构端和一开放端，所述孔状结构端具有一个或多个允许液体通过的孔，所述过滤部件容置部件的开放端与所述药物容置部件的孔状结构端可盖合形成用于容纳所述过滤部件的腔体；所述药物容置部件的开放端为开口的管状结构，用于容纳药物颗粒或多丸。
  12. 一种口服给药递送装置，其特征在于，其包括如权利要求8～11至少一项所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置外接于所述第一开口的自由端，并使用于承载药物颗粒或多丸的空间与所述内腔相连通。
  13. 如权利要求12所述的口服给药递送装置，其特征在于，所述药物容置装置置于所述管状构件外，并通过固定套设方式或螺纹连接方式维持于所述管状构件的第一开口处；
    和/或，所述第二开口处还设有一用于封口的顶盖；
    和/或，所述管状部件为一直吸管；所述直吸管上较佳地具有至少1个褶皱部结构；较佳地，所述褶皱部结构具有1对翼部和1个转折端，所述褶皱部结构可沿所述管状构件轴向拉伸或收缩，并在拉伸时形成湍流；
    和/或，所述管状部件具有至少2个管段，所述管段之间密封连接并可沿所述管状构件轴向拉伸或收缩；所述管状构件呈拉伸状态时形成具有至少1个台阶结构的湍流产生部件；
    其中，当所述管段的数量为3个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的外径小于所述第一管段的内径，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段的内径、第二管段的外径、内径和第三管段的外径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩；
    其中，当所述管段的数量为4个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的内径与第四管段的内径相同，其中，所述第二管段的内径小于所述第一管段，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段至第四管段的内径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩。
  14. 一种口服给药递送装置，其中包括如权利要求8～11至少一项所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口； 所述药物容置装置设于所述内腔中、且靠近所述第一开口处，并使用于承载药物颗粒或多丸的空间与所述第二开口相连通；所述第一开口的直径小于所述药物容置装置的最小直径。
  15. 如权利要求14所述的口服给药递送装置，其特征在于，所述第二开口的直径小于所述药物容置装置的最小直径；
    和/或，所述第二开口处还设有一用于封口的顶盖；
    和/或，所述管状构件的结构如权利要求13所述。
  16. 一种固体口服制剂的药物容置装置，其特征在于，其包括一过滤部件和用于支撑所述过滤部件的支撑部件，所述过滤部件和所述支撑部件相互配合形成用于承载药物颗粒或多丸的空间，所述过滤部件具有一个或多个允许液体通过的孔道；所述孔道在所述过滤部件的内部以上下错综交叉的方式分布，所述过滤部件上还设有一水溶性高分子材料层，从而使所述药物颗粒或多丸无法通过。
  17. 如权利要求16所述的药物容置装置，其特征在于，所述的过滤部件为滤膜；
    所述滤膜的形状较佳地为圆柱状结构；
    所述滤膜的厚度较佳地为0.3～20mm，更佳地为0.5～15mm，进一步更佳地为0.5～10mm；
    较佳地，将所述滤膜的上下表面以及内部的孔道都设置为不规则的、且错综交叉的结构，更佳地为海绵状的多孔结构，或者由多层纤维无规则层叠排列、压制而成的蓬松结构；
    所述的滤膜的孔径较佳地为1-500μm，更佳地为20～400μm，进一步更佳地为40-300μm；
    所述的滤膜的有效直径较佳地为4-20mm，更佳地为6-15mm，进一步更佳地为8mm-12mm；
    和/或，
    所述药物颗粒或多丸的粒径为1-5000μm，较佳地为25-2000μm，更佳地为50-1000μm；
    较佳地，当所述药物颗粒或多丸的粒径范围为50-1000μm时，所述过滤部件的孔径为40-300μm；
    和/或，
    所述药物颗粒或多丸包含的活性药物成分包括但不限于以下的一种或多种：达比加群酯或其药学上可接受的盐、阿哌沙班、利伐沙班、左旋多巴-卡比多巴、孟鲁司特、兰索拉唑、奥美拉唑、埃索美拉唑、阿莫西林、克拉霉素、阿奇霉素、甲硝唑、利福平、 柳氮磺吡啶、对乙酰氨基酚、右美沙芬、多西拉敏、伪麻黄碱、苯海拉明、安非他命、哌甲酯、地拉罗司、ivacaftor、lumacaftor、他克莫司、地西泮、氯巴占、氨己烯酸、波生坦、褪黑素、生物素、二巯基丁二钠、氨氯地平和艾司洛尔。
  18. 如权利要求16-17至少一项所述的药物容置装置，其特征在于，所述水溶性高分子材料层形成的结构为如下两种：在所述的滤膜的上表面或下表面形成一层连续的水溶性高分子材料层，或者完全堵塞所述的滤膜的孔道、形成一个完整、致密的水溶性高分子材料层；
    和/或，所述的水溶性高分子材料层的溶解时间为小于等于10s；
    和/或，所述的水溶性高分子材料层中高分子材料的分子量为2000-200000，较佳地为2000-100000；
    和/或，所述的水溶性高分子材料层中所述高分子材料的种类选自羟丙甲纤维素、共聚维酮、羟丙基纤维素、羟乙基纤维素、聚维酮、聚乙二醇、明胶、泊洛沙姆、黄原胶和尤特奇中的一种或多种；
    和/或，所述水溶性高分子材料层的成型过程中，高分子材料增重为0.01-60mg/cm 2，较佳地为0.5-30mg/cm 2。
  19. 如权利要求16-18至少一项所述的药物容置装置，其特征在于，所述支撑部件的结构为如下结构中的任意一种：
    所述支撑部件包括一上支撑部件、一下支撑部件，所述上支撑部件和所述下支撑部件可相互盖合、并将所述过滤部件夹持在中间，所述上支撑部件与所述过滤部件的上方空间用于容纳药物颗粒或多丸；
    或者，所述支撑部件包括一过滤部件容置部件和一药物容置部件，所述过滤部件容置部件和所述药物容置部件均具有一孔状结构端和一开放端，所述孔状结构端具有一个或多个允许液体通过的孔，所述过滤部件容置部件的开放端与所述药物容置部件的孔状结构端可盖合形成用于容纳所述过滤部件的腔体；所述药物容置部件的开放端为开口的管状结构，用于容纳药物颗粒或多丸。
  20. 一种口服给药递送装置，其特征在于，其包括如权利要求16-19至少一项所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置外接于所述第一开口的自由端，并使用于承载药物颗粒或多丸的空间与所述内腔相连通。
  21. 如权利要求20所述的口服给药递送装置，其特征在于，所述药物容置装置置于所 述管状构件外，并通过固定套设方式或螺纹连接方式维持于所述管状构件的第一开口处；
    和/或，所述第二开口处还设有一用于封口的顶盖；
    和/或，所述管状部件为一直吸管；所述直吸管上较佳地具有至少1个褶皱部结构；较佳地，所述褶皱部结构具有1对翼部和1个转折端，所述褶皱部结构可沿所述管状构件轴向拉伸或收缩，并在拉伸时形成湍流；
    和/或，所述管状部件具有至少2个管段，所述管段之间密封连接并可沿所述管状构件轴向拉伸或收缩；所述管状构件呈拉伸状态时形成具有至少1个台阶结构的湍流产生部件；
    其中，当所述管段的数量为3个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的外径小于所述第一管段的内径，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段的内径、第二管段的外径、内径和第三管段的外径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩；
    其中，当所述管段的数量为4个时：其由所述第一开口至所述第二开口方向上的第一管段的内径与第三管段的内径相同，第二管段的内径与第四管段的内径相同，其中，所述第二管段的内径小于所述第一管段，且每一管段可沿其他管段轴向拉伸或收缩；或，其由所述第一开口至所述第二开口方向上的第一管段至第四管段的内径逐渐减小，且每一管段可沿其他管段轴向拉伸或收缩。
  22. 一种口服给药递送装置，其特征在于，其包括如权利要求16-19至少一项所述的药物容置装置，所述口服给药递送装置还包括一管状构件，所述管状构件具有两端开口及内腔，其一端开口为第一开口，另一端开口为第二开口，所述内腔连通所述第一开口和第二开口；所述药物容置装置设于所述内腔中、且靠近所述第一开口处，并使用于承载药物颗粒或多丸的空间与所述第二开口相连通；所述第一开口的直径小于所述药物容置装置的最小直径。
  23. 如权利要求22所述的口服给药递送装置，其特征在于，所述第二开口的直径小于所述药物容置装置的最小直径；
    和/或，所述第二开口处还设有一用于封口的顶盖；
    和/或，所述管状构件的结构如权利要求21所述。
PCT/CN2020/079017 2019-09-30 2020-03-12 固体口服制剂的药物容置装置及含其的口服给药递送装置 WO2021062987A1 (zh)

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