CN110731949A - capsules and application method thereof - Google Patents
capsules and application method thereof Download PDFInfo
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- CN110731949A CN110731949A CN201810796311.1A CN201810796311A CN110731949A CN 110731949 A CN110731949 A CN 110731949A CN 201810796311 A CN201810796311 A CN 201810796311A CN 110731949 A CN110731949 A CN 110731949A
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- capsule
- capsules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
Abstract
The invention provides capsules, which comprise an outermost outer-layer capsule, wherein at least inner-layer capsules or at least membranes are contained in the outer-layer capsule, the outer-layer capsule has toughness, when the outer-layer capsule is acted by external force, the inner-layer capsules or the membranes are damaged or opened, but the outer-layer capsules are not damaged, each layer of capsules or each compartment independently bears content, such as medicinal components, biological reaction reagents or solutions, the capsules are independent and do not contact with each other during manufacturing, transportation and storage, the components are mixed when the capsules are needed to be taken or used, and the reaction is completed in the capsules.
Description
Technical Field
The present invention pertains to containers for medical or pharmaceutical purposes, in particular capsules carrying pharmaceutical agents or bioreaction solutions and methods of use thereof.
Background
The capsule is a container for holding medicines, such as powder or granular medicines which are irritant to esophagus and gastric mucosa, and can also effectively solve the problems by coating the capsule for medicines which are volatile, easily decomposed by saliva or have poor taste.
The present biomacromolecule medicine plays more and more important roles in clinical treatment of diseases, particularly protein medicines, but the purification process of the biomacromolecule medicine is complex, the storage condition is generally higher in requirement, and the biomacromolecule medicine is easily influenced by external environment, such as pH value, protease existing in the environment, and the like, which greatly increases the use cost of the medicine and limits the universal use of the medicine, the treatment effect of the freshly synthesized biomacromolecule medicine is optimal, a high-efficiency in-vitro biosynthesis system (including an in-vitro protein synthesis system) convenient for transportation and use can meet the requirement, but the transportation condition and the reaction condition of the existing in-vitro protein synthesis system can not meet the requirement.
Disclosure of Invention
In view of the above, the present invention solves the disadvantages of the existing capsule structure, and provides capsules and a method for using the same, which can independently carry contents, such as pharmaceutical ingredients, bioreaction reagents or solutions, in each layer or each separate compartment of the capsule, are independent from each other and do not contact each other during manufacturing, transportation and storage, and when the capsule needs to be taken or used, the ingredients are mixed and the reaction is completed in the capsule, thereby achieving the purpose of fresh production of pharmaceutical molecules, convenient preparation and storage, avoiding the mutual reaction of the ingredients and improving the use effect.
The technical scheme adopted by the invention for solving the technical problems is that capsules can be multilayer capsules, the multilayer capsules can be at least two layers, and can be 2 layers, 3 layers, 4 layers or even more, the multilayer capsules comprise outermost outer capsules, at least inner capsules are contained in the outer capsules, the outer capsules have toughness, the inner capsules have definite brittleness or cracking property, so that when the outer capsules are subjected to external force, such as extrusion, pressing, biting force and the like, the inner capsules are broken or opened, substances stored in different capsule intervals are mixed, the outer capsules are not broken in vitro, the outer capsules can be dissolved and/or digested in vivo, so that the inner capsules are broken under the external force when the outer capsules need to be taken or used, the contents in the inner capsules are mixed or reacted in reaction containers of the outer capsules, and the contents are mixed or reacted before the taking or use, the problems of content inactivation in advance or the effect reduction and the like are avoided, and the contents in the outer capsules and/or the outer capsules are effectively dissolved in vivo.
capsules are optionally provided, which have a plurality of compartments, and specifically, which have an outer capsule, wherein at least layers of membranes are arranged in the outer capsule to separate the outer capsule into a plurality of chambers, wherein the membranes have a brittleness or a crack-splitting property of , so that when the outer capsule is subjected to external force, such as squeezing, pressing, biting force and the like, the membranes are broken or opened to mix substances stored in different chambers, and the outer capsule is not broken in vitro, and the outer capsule can be dissolved and/or digested in vivo.
, the inner layer capsule can be wrapped layer by layer in the form of a collar, or at least or more independent inner layer capsules can be arranged in the outer layer capsule.
Further , the inner capsule can be divided into at least two distinct compartments.
, the inner side of the inner capsule or part of the membrane is provided with a protrusion, under the action of external force, the protrusion of the inner capsule (or membrane) punctures itself, preferably, the inner side of the inner capsule is provided with a protrusion and a corresponding bubble part protruding to the inner capsule, or another position of the membrane or another membrane is provided with a bubble part, during the application of force, the protrusion punctures the corresponding bubble part, so that the contents in different capsules are mixed, the protrusion is structure of the inner capsule, concretely, the protrusion is in any shape with tip, such as triangle, circle, square, ellipse, etc.
Alternatively, the inner side of each layer of capsules may be provided with at least inwardly projecting lugs which will pierce through the inner capsules during application of force to mix the contents of the different layers of capsules, in particular the lugs may be of any shape having a pointed tip, or of course only the inner side of the outer capsules may be provided with at least inwardly projecting lugs which pierce through each inner capsule (or each membrane) during application of force to mix the contents of the capsules.
Alternatively, the inner capsule (or membrane) is supported by the outer capsule by at least connection portions, and the outer capsule is pressed open and broken by the connection portions during the application of force, so that the contents in the different capsules are mixed, and in particular, the connection portions are in any shape for connecting the inner capsule (or membrane) and the outer capsule, and the connection portions can be arranged at any position.
Or the inner capsule (or the diaphragm) is provided with a movable plug, preferably, the movable plug is head large and head small structure, so that the movable plug is conveniently separated under the action of external force, when the external force is applied, the movable plug on the inner capsule moves towards the outer capsule or towards the inner capsule under the action of internal or external pressure, so that the contents in different capsules are mixed, and for the diaphragm, when the external force is applied, the movable plug on the diaphragm is separated, so that the contents in different cavities are mixed.
Alternatively, at least part of the inner capsule (or septum) is a frangible portion which is broken by external force or pressure of the contents therein during application of force to mix the contents in different capsules (or different compartments), the frangible portion being a portion which is more frangible than the rest of the inner capsule (or septum) and which is more easily broken.
Or, besides the required contents, the inner capsule or the compartment between the two layers of membranes is additionally filled with gas, so that the expansion degree of the inner capsule or the compartment between the two layers of membranes is close to the critical value of breakage, and the inner capsule or the compartment is easy to break when external force is applied, and the filling gas is selected from any gases of helium, neon, argon, krypton, xenon, nitrogen, oxygen and the like or the combination thereof, which can help to protect the stability of the inner substances, and can also be the gas environment required by the reaction when the contents to be mixed need certain gas conditions to react, such as oxygen.
It should be noted that are optional for the means of breaking or opening, and any combination of the above means may be used.
, the bubble portion and the protrusion of the inner capsule (or septum) are molded with the inner capsule (or septum) , and the protrusion is molded with the capsule .
Further , the contents of the inner capsule (or membrane) and the outer capsule are not required to be in the form of solution, suspension, solid, semi-solid, gas, emulsion, suspension, flowable powder, granules, etc., the contents can be in the form of a biopharmaceutical ingredient, such as an active pharmaceutical ingredient, or a material for a cell-free protein synthesis system, preferably the outer capsule and the inner capsule (or membrane closest to the outer capsule) carry a liquid, such as water or an aqueous solvent, while the inner capsule (or membrane) in direct contact with the contents of the outer capsule is not dissolved or is hydrophobic to ensure the independence of the contents carried by the inner and outer capsules (or compartments) prior to administration or use, preferably the outer surface of the inner capsule (or membrane) is coated or coated with a protective coating, or the inner capsule (or membrane) is composed of water-insoluble ingredients.
For the protective coating, ingredients may be selected from, but are not limited to, vegetable oils such as, but not limited to, canola oil, peanut oil, sunflower oil, safflower oil, linseed oil, tung oil, rapeseed oil, soybean oil, olive oil, sesame oil, coffee oil, brown rice oil, almond oil, hazelnut oil, coconut oil, wheat germ oil, castor oil, shea butter oil, corn oil, camellia oil, cottonseed oil, evening primrose oil, jojoba oil, palm oil, peppermint oil, vanilla oil, rose hip oil, macadamia nut oil, orange oil, lemon oil, grapefruit oil, lime oil, cherry oil, apple oil, strawberry oil, grape seed oil, etc., of the above ingredients may also be selected in any combination.
The modified vegetable oil, such as alkoxylated sunflower oil or soybean oil, synthetic (tri) glycerides, such as industrial mixtures of C-C fatty acids, di-and triglycerides, fatty acid alkyl esters, such as methyl or ethyl esters of vegetable oils, fatty acid alkyl esters based on C-C fatty acids, mineral oil and mixtures thereof suitable hydrophobic protective coatings are, but not limited to, esters of fatty alcohols with 6-18, preferably 8-10 carbon atoms, such as lauryl fatty alcohol, linear C-C fatty acids with linear or branched C-C fatty alcohols, such as fatty alcohol di-or lauryl fatty acids, such as fatty alcohol di-or lauryl fatty alcohol, fatty alcohol di-or lauryl fatty alcohol with linear or branched fatty alcohol, such as fatty alcohol di-or lauryl fatty alcohol, fatty alcohol di-or lauryl fatty acid, fatty alcohol di-or lauryl fatty alcohol, or lauryl fatty alcohol, fatty alcohol di-or lauryl fatty alcohol, lauryl alcohol, stearyl alcohol, lauryl alcohol, stearyl alcohol, lauryl.
More specifically, the silicone oil includes cyclopentasiloxane, cyclohexasiloxane, cycloheptasiloxane, cyclomethicone, methylphenylmethylsilicone, cyclotetrasiloxane, cyclotrisiloxane, dimethicone, decanoyldimethicone, octylpolytrimethylsiloxane, octylmethicone, cetearylmethylsiloxane, polyhexamethylsiloxane, hexylmethicone, dodecylmethicone, tetradecylpmethicone, phenyl methicone, stearyl dimethicone, trifluoropropylmethicone, cetyl dimethicone, tolylpolysiloxane, decamethylcyclopentasiloxane, methylpolytrimethicone, phenyl trimethicone, and the like, but is not limited thereto.
The animal fat and oil can be, but not limited to, beef tallow, mutton tallow, lamb tallow, lard, sperm oil, egg yolk oil, shark liver oil, emu oil, mink oil, etc.
The mineral oil may be paraffin, vaseline, ceresin, liquid paraffin, beeswax, carnauba wax, and combinations thereof, but is not limited thereto.
The synthetic oil may be a silicone oil, a hydrocarbon oil, an ester oil, or the like, and each specific component is the same as in the case of removing the natural oil from the silicone oil, the hydrocarbon oil, and the ester oil as described above.
The protective coating may also be selected from the group consisting of fat soluble vitamins (e.g., vitamins A, D, E and K), tocotrienols, carotenoids, xanthophylls (e.g., lycopene, lutein, astaxanthin, zeaxanthin), fat soluble nutraceuticals including phytosterols, phytosterols and esters thereof, coenzyme Q10 and panthenol, hydrophobic amino acids and peptides, essential oils and extracts, and fatty acids suitable omega-3 fatty acids include, for example, Conjugated Linolenic Acid (CLA), omega-6 fatty acids, and omega-3 fatty acids suitable omega-3 fatty acids include, for example, short chain omega-3 fatty acids such as α -linolenic acid (ALA) derived from plant sources such as linseed, and long chain omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) long chain omega-3 fatty acids may be derived from, for example, marine or fish oils such oils may be extracted from various types of fish or marine animals such as anchovies, capelin, cod, menhaden, sarns and shark, salmon and other marine tissues including marine oils such as omega-3 fatty acids, and any combination thereof.
The protective coating can also be selected from arachidonic acid, prostaglandin and its derivatives, sucrose fatty acid ester, propylene glycol fatty acid ester, glycerin fatty acid ester, long chain fatty acid triglyceride, medium chain fatty acid triglyceride, zwitterionic emulsifier, and lecithin.
Fats, oils, waxes, resins, emulsifiers or mixtures thereof, preferably of food grade. Preferably, animal oils and fats, fully hydrogenated vegetable or animal oils, unsaturated, fully hydrogenated vegetable or animal oils, partially hydrogenated vegetable or animal oils, unsaturated, partially hydrogenated or fully hydrogenated fatty acids, monoglycerides and diglycerides of unsaturated, partially hydrogenated or fully hydrogenated fatty acids, monoglycerides or diglycerides of unsaturated, partially hydrogenated or fully hydrogenated esterified fatty acids, unsaturated, partially hydrogenated or fully hydrogenated free fatty acids, other emulsifiers, animal waxes, vegetable waxes, mineral oils, synthetic waxes, natural and synthetic resins and mixtures thereof. Free fatty acids such as but not limited to stearic acid, palmitic acid and oleic acid. Other emulsifiers such as, but not limited to, polyglycerol esters, sorbitol esters of fatty acids. Animal waxes such as, but not limited to, beeswax, lanolin, shell wax, or insect wax. Vegetable waxes are such as, but not limited to, carnauba wax (carnauba wax), candelilla wax (candelilla wax), bayberry wax (bayberry wax), sugar cane wax (sugar cane wax). Mineral oils such as, but not limited to, paraffin, microcrystalline petroleum, ozocerite (ozocerite), ceresin (ceresin), or montan (montan). Natural resins such as rosin, balsam, shellac and zein.
As a non-limiting example of , the cellulose-based polymer compound may be any one or more selected from ethyl cellulose, cellulose acetate such as cellulose acetate propionate and cellulose acetate butyrate, nitrocellulose, cellulose acetate butyrate and the like, the polystyrene-based polymer compound may be any one or more selected from polystyrene, poly-p-methylstyrene, poly-m-methylstyrene, poly-ethyl styrene, poly-m-ethyl styrene, poly-p-chlorostyrene, poly-m-chlorostyrene, poly-chloromethyl styrene, poly-m-chloromethyl styrene, poly-p-butoxy styrene, poly-m-butoxy styrene and poly-t-butoxy styrene and the like, and the acrylate-based polymer compound may be any one or more selected from polymethyl methacrylate, polyethyl methacrylate, polypropylene methacrylate, n-butyl methacrylate, polyisobutyl methacrylate, poly-tert-butyl methacrylate, poly-2-ethylhexyl methacrylate, poly-n-lauryl methacrylate, poly-octyl methacrylate, poly-octadecyl methacrylate, poly-glycidyl methacrylate and poly (ethylene glycol methacrylate).
The water-insoluble polymer component may be selected from polyethylene, polypropylene, polyvinyl chloride, polyvinyl acetate, polyurethane, polyester, ammonio methacrylate copolymer, acrylic resin, shellac, zein starch, acrylate, methacrylate, a mixture of acrylate and methacrylate, polycarbonate, polyethylene terephthalate (polyethylene terephthalate), and polyurethane, but is not limited thereto.
, the inner layer capsule and the outer layer capsule are both body structures or the inner layer capsule and the outer layer capsule are both composed of split structures of a capsule body and a capsule cap or the inner layer capsule and the outer layer capsule are the combination of the body structure and the split structures, preferably, the inner layer capsule is composed of a capsule body and a capsule cap, and the outer layer capsule is body structure, so that the outer layer capsule is prevented from being undesirably separated to generate leakage when external force is applied, the capsule body and the capsule cap of the inner layer capsule are separated under the action of external force, the reaction or mixing of contents in the multilayer capsule is facilitated, the leakage is prevented, if the inner layer capsule is body structure, the inner layer capsule is damaged under the action of external force, if the inner layer capsule is split structure, the inner layer capsule is damaged or the capsule body and the capsule cap are opened under the action of external force, and for the multi-compartment capsule, the diaphragm and the multilayer capsule body are molded or spliced to form the multi-compartment capsule.
, the outer layer of the capsule has elasticity, and can be partially or completely recovered by elastic recovery after the external force disappears.
Further , the outer layer capsule is made transparent or provided with viewing ports to allow for a determination of whether the inner layer capsule (or membrane) is broken, i.e., whether the contents of the inner layer capsule have been mixed.
, the inner layer capsule (or membrane) and the outer layer capsule can be the same or different, and the inner layer capsule and the outer layer capsule can be the same or different, and the shape is not limited in detail, and can be any shape suitable for capsule in existence;
, the outer layer capsule is made of bio-friendly material which can be dissolved and/or digested in the environment of digestive system;
, the inner capsule (or membrane) can be fixed at any position inside the outer capsule or can be free inside the outer capsule, when the inner capsule is free inside the outer capsule, it is preferable that the inner side of the outer capsule has a protrusion to facilitate the breakage or opening of the free inner capsule;
, the minimum external force of the inner capsule (or membrane) is determined according to the thickness, composition, water content, etc of the inner capsule (or membrane);
, the capsule contents can be the reaction material of medicine or cell-free protein synthesis system, or the nutritive components.
Meanwhile, kinds of capsules are provided, when in use, the outer capsule is acted by external force, so that the inner capsule or the diaphragm is broken or opened, the outer capsule is not broken, and the contents in each layer or each partition cavity are mixed or reacted in the outer capsule.
The capsule has the advantages and positive effects that corresponding contents such as medicinal ingredients, biological reaction reagents or solutions can be filled in the inner and outer capsules or different separate cavities, when the capsule needs to be taken or used, the inner capsule or the diaphragm is damaged through the action of external force, so that the contents in the inner and outer capsules or different separate cavities are mixed or react, according to the concept of 'existing preparation in use', the existing contents are prevented from being mixed at to generate chemical reaction, the medicinal effect is reduced or tends to disappear before the capsule is taken or used, and the protein medicaments such as antibodies generated by a cell-free protein synthesis system can be prevented from generating unnecessary inactivation and degradation in the change of an external environment.
Drawings
Corresponding reference characters indicate corresponding parts throughout the several views of the drawings, in which: 1-outer layer capsule; 2-inner layer capsule; 3-a viewing port; 4-a bubble portion; 5-a protrusion; 6-a projection; 7-a connecting part; 8-a movable plug 8; 9-a fragile portion 9; 10-a separator;
FIG. 1a is a schematic view of a multi-layer capsule;
FIG. 1b is a schematic view of a multilayer capsule comprising a viewing port;
FIG. 2a is a schematic view of a multi-layer capsule in the form of a layer-by-layer wrap in the form of a collar;
FIG. 2b is a schematic view of a multi-layered capsule with an inner capsule secured within an outer capsule;
FIG. 2c is a schematic view of a multilayer capsule with inner capsules free within outer capsules;
FIG. 2d is a schematic view of a multi-layered capsule comprising an inner capsule formed by chambers;
FIG. 2e is a schematic view of a multi-layered capsule comprising a layer-by-layer wrapped inner layer capsule in the form of a collar and a single layer inner layer capsule;
FIG. 3a is a schematic view of a multi-layered capsule having an inner layer capsule with a bubble portion and a protrusion portion;
FIG. 3b is a schematic view of a multi-layered capsule with a protrusion in the inner layer;
FIG. 4 is a schematic view of a multi-layered capsule having a bulge in the outer layer of the capsule;
FIG. 5a is a schematic view of a multi-layered capsule with the attachment portion in a left-right position;
FIG. 5b is a schematic view of a multi-layered capsule with the connecting portion in an up-down position;
FIG. 6 is a schematic view of a multi-layer capsule with a movable plug;
FIG. 7 is a schematic view of a multi-layer capsule having a frangible portion;
fig. 8 is a schematic view of another embodiment of the present application of a multi-compartment capsule.
Detailed Description
The capsule according to the present invention will be described in detail below with reference to the accompanying drawings. The drawings described below are provided by way of example in order to fully convey the concept of the invention to those skilled in the art. Therefore, the present invention is not limited to the drawings set forth below, and may be embodied in other forms, and the drawings set forth below are provided to clarify the idea of the present invention.
Example 1
kinds of capsules, which are multilayer capsules, the multilayer capsules are at least two layers, which can be 2 layers, 3 layers, 4 layers or even more, as shown in fig. 1a, taking a double-layer capsule as an example, the multilayer capsule comprises an outermost outer capsule 1, at least inner capsules 2 are contained in the outer capsule 1, the outer capsule 1 has toughness, the inner capsules 2 have definite brittleness or cracking property, so that when the outer capsule 1 is acted by external force, such as extrusion, pressing, biting force and the like, the inner capsules 2 are broken or opened, so that substances stored in different capsule regions are mixed, the outer capsule 1 is not broken when the outer capsule 1 is acted by the external force, the outer capsule 1 can be dissolved and/or digested in vivo, so that when the inner capsule 2 is broken under the external force when taking or using, the contents in each inner capsule 2 are mixed or reacted in a reaction container of the outer capsule 1, so that the contents are mixed or reacted before taking or using, and the multilayer capsule 1 and the effective ingredients in the body are released.
The outer capsule is made transparent or provided with viewing ports 3 (fig. 1 b) so that it can be determined whether the inner capsule is broken, i.e. the contents of the inner capsule are mixed, as shown in fig. 2a, the inner capsule can be wrapped layer by layer in the form of a collar, as shown in fig. 2b and 2c, or at least or more inner capsules independent of each other can be provided inside the outer capsule, the inner capsules can be fixed at any position inside the outer capsule (fig. 2 b) or free inside the outer capsule (fig. 2 c), the exemplary illustrations in fig. 2b and 2c have 2 inner capsules, but not limited thereto, the inner capsules can be provided in the form of or more inner capsules, as shown in fig. 2d, the inner capsules can be divided into different chambers, at least two chambers, it should be noted that the inner capsules located inside the outer capsule can also be wrapped layer by layer in the form of a collar and at least or a combination of multiple independent inner capsules, i.e. both the inner capsules are provided in the form of a collar ;
in fig. 3a, the inner layer capsule is shown to have the bubble portion 4 and the protrusion portion 5, specifically, the inner side of the inner layer capsule 2 may be provided with at least bubble portions 4 protruding towards the inside of the capsule and the protrusion portions 5 protruding towards the inside of the capsule correspondingly, during the application of force, the protrusion portions 5 pierce the corresponding bubble portions 4, so as to mix the contents in the capsules of different layers, the protrusion portion 5 is body structure of the inner layer capsule, specifically, the protrusion portion 5 is any shape with tip, such as triangle, circle, square, ellipse, etc., the bubble portion 4 and the protrusion portion 5 of the inner layer capsule 2 are formed with the body of the inner layer capsule 2 , of course, as shown in fig. 3b, the bubble portion 4 may be omitted, and under the external force, at least protrusion portions 5 of the inner layer capsule 2 may pierce themselves.
The contents filled in the inner capsule 2 and the outer capsule 1 are not particularly required, and can be solution, suspension, solid, semisolid, gas, emulsion, suspension, flowable powder, particles and the like; the contents may be a biopharmaceutical ingredient, e.g., an active pharmaceutical ingredient, or a raw material for a cell-free protein synthesis system; preferably, the outer capsule 1 and the inner capsule 2 carry a liquid (i.e., the outer capsule carries a liquid such as water or an aqueous solvent) therebetween, while the inner capsule 2, which is in direct contact with the contents of the outer capsule 1, is not dissolved by the liquid or has hydrophobicity to ensure independence of the contents carried by the inner and outer capsules prior to administration or use; preferably, a protective coating is applied or coated on the outer surface of the inner capsule 2, or the inner capsule 2 is composed of water-insoluble components. The choice of protective coating and water-insoluble ingredients can be any of those known in the art that can act as a barrier to liquid contact with the inner capsules or are hydrophobic, preferably the various components mentioned in the summary section, and will not be described further herein.
The inner layer capsule 2 and the outer layer capsule 1 are both body structures or the inner layer capsule 2 and the outer layer capsule 1 are both composed of split structures of a capsule body and a capsule cap or the inner layer capsule 2 and the outer layer capsule 1 are the combination of the body structure and the split structures, preferably, the inner layer capsule 2 is composed of the capsule body and the capsule cap, and the outer layer capsule 1 is body structure, so that the outer layer capsule 1 is prevented from being undesirably separated to generate leakage when external force is applied, the capsule body and the capsule cap of the inner layer capsule 2 are separated under the action of the external force, the content in the capsule is favorably reacted or mixed without leakage, if the inner layer capsule 2 is body structure, the inner layer capsule is damaged under the action of the external force, and if the inner layer capsule 2 is split structure, the inner layer capsule is damaged or the capsule body and the capsule cap are opened under the action of the external force.
The inner layer capsule 2 and the outer layer capsule 1 may be made of the same or different materials, and the inner layer capsule 2 and the outer layer capsule 1 may be the same or different in shape, and the shape is not particularly limited, and may be any shape suitable for a capsule. Preferably, the material of the outer layer capsule 1 has elasticity, and can be partially or completely restored by the elasticity after the external force disappears. The raw materials for making the inner layer capsule 2 and the outer layer capsule 1 are not particularly limited, and can be any raw materials suitable for making capsules in the prior art; preferably, the outer capsule 1 is made of a bio-friendly material that can be dissolved and/or digested in the digestive system. The minimum external force value that the inner capsule 2 can bear is determined according to factors such as the thickness, the composition, the water content and the like of the inner capsule 2. The content of the capsule can be a reaction raw material of a medicine or a cell-free protein synthesis system, and can also be any reactant needing to be mixed, such as nutritional ingredients.
alternatively, as shown in FIG. 4, at least the inner side of the outer capsule 1 is provided with at least inwardly protruding projections 6, and during the application of force, the projections 6 will pierce the inner capsule 2 to mix the contents of the different capsules, specifically, the projections 6 may be of any shape having pointed tips, or, of course, only the inner side of the outer capsule 1 may be provided with at least inwardly protruding projections 6, and during the application of force, the projections 6 pierce each of the inner capsules to mix the contents of the different capsules, and when the inner capsule 2 is free inside the outer capsule 1, it is preferred that the inner side of the outer capsule 1 is provided with projections 6 to facilitate the breakage or opening of the free inner capsule, wherein the projections 6 are integrally formed with the capsule .
alternatively, the inner capsule 2 is supported on the outer capsule 1 by at least connecting parts 7, and during the application of force, the inner capsule 2 is pressed open and broken by the connecting parts 7, so that the contents in the different capsules are mixed, specifically, the connecting parts 7 are any shape connecting the inner capsule and the outer capsule, and the connecting parts 7 can be arranged at any position, illustratively, at the left and right ends of the inner capsule 2 (fig. 5 a) or at the upper and lower ends of the inner capsule 2 (fig. 5 b).
alternatively, as shown in FIG. 6, the inner capsule 2 has a movable plug 8, the movable plug 8 can be arranged at any position on the inner capsule 2, when external force is applied, the movable plug 8 on the inner capsule 2 is acted by internal or external pressure and moves towards the outer capsule 1 or the inner capsule 2, so as to mix the content in the different capsules, preferably, the movable plug 8 is with a big head and a small head, with a small head, so as to be conveniently detached when external force is applied.
alternatively, at least part of the inner capsule is a brittle portion 9, as shown in fig. 7, wherein the brittle portion 9 is broken under the pressure of external force or internal content during the application of force, so as to mix the content in different capsules, and the brittle portion 9 is a portion which is more brittle than other parts of the inner capsule, and is easy to break.
alternatively, the inner capsule is filled with a gas selected from any or combination of helium, neon, argon, krypton, xenon, nitrogen, oxygen, etc. which helps to stabilize the contents to be mixed and also provides a gas environment for the reaction, such as oxygen, when the contents to be mixed require certain gas conditions to react.
It should be noted that are optional for the means of breaking or opening, and any combination of the above means may be used.
Example 2
capsules, which are multi-compartment capsules, the multi-compartment capsules comprise an outermost outer capsule 1, wherein at least layers of membranes 10 are contained in the outer capsule 1, the outer capsule 1 has toughness, and the membranes 10 have -determined brittleness or cracking performance, so that when the outer capsule 1 is acted by external force, such as squeezing, pressing, biting force and the like, the membranes 10 are broken or opened, so that substances stored in different compartments are mixed, the outer capsule 1 is not broken when the external force is acted, the outer capsule 1 can be dissolved and/or digested in vivo, so that when the capsules are needed or used, the membranes 10 are broken under the external force, the contents in different compartments are mixed or reacted in a reaction container of the outer capsule 1, so that the contents are mixed before the capsules are taken or used, and after the multi-compartment capsules are taken or used, the outer capsule 1 is dissolved and/or digested in vivo, so that effective ingredients in the multi-compartment capsules are released into the body.
The outer layer capsule is made to be transparent or is provided with viewing ports 3, so that whether the diaphragm 10 is broken or not can be judged, namely whether the contents in different compartments are mixed or not can be judged, the diaphragm 10 can be provided with bubble parts 4 and protrusions 5, specifically, the end of the diaphragm 10 can be provided with at least protruding bubble parts 4, the other end of the diaphragm 10 or the other diaphragm 10 is correspondingly provided with protruding protrusions 5, the protrusions 5 puncture the corresponding bubble parts 4 in the process of applying force, so that the contents in different compartments are mixed, the protrusions 5 are body structures of the diaphragm 10, specifically, the protrusions 5 are in any shapes with pointed tips, such as triangles, circles, squares, ellipses and the like, the bubble parts 4 and the protrusion parts 5 of the diaphragm 10 are molded with the 10 body of the diaphragm 10, of course, the bubble parts 4 can be omitted, and the at least protrusion parts 5 of the diaphragm 10 can be directly punctured under the action of external force.
For the contents, the contents filled in different compartments have no specific requirement, and can be solution, suspension, solid, semisolid, gas, emulsion, suspension, flowable powder, particles and the like; the contents may be a biopharmaceutical ingredient, e.g., an active pharmaceutical ingredient, or a raw material for a cell-free protein synthesis system; preferably, the outer capsule 1 carries a liquid, such as water or an aqueous solvent, between its closest membrane, while the membrane 10 in direct contact with the content of the outer capsule 1 is not dissolved by this liquid, or is hydrophobic, to ensure independence of the content carried in the different compartments before administration or use; preferably, a protective coating is applied or coated on the outer surface of the separator 10, or the separator 10 is composed of a water-insoluble component. The choice of protective coating and water-insoluble ingredients can be any of those known in the art that can act as a barrier to liquid contact with the inner capsules or are hydrophobic, preferably the various components mentioned in the summary section, and will not be described further herein.
The diaphragm 10 and the outer capsule 1 are both body structures or the outer capsule 1 is composed of a split structure of a capsule body and a capsule cap, preferably, the outer capsule 1 is body structure, thereby ensuring that the outer capsule 1 does not have unexpected separation to generate leakage when external force is applied.
The material of the membrane 10 and the outer capsule 1 may be the same or different, and the shape of the membrane 10 and the outer capsule 1 is not particularly limited, and may be any shape suitable for the membrane and the capsule. Preferably, the material of the outer layer capsule 1 has elasticity, and can be partially or completely restored by the elasticity after the external force disappears. The raw materials for making the membrane 10 and the outer layer capsule 1 are not particularly limited, and can be any raw materials suitable for making in the prior art; preferably, the outer capsule 1 is made of a bio-friendly material that can be dissolved and/or digested in the digestive system. The minimum external force value that the separator 10 can withstand is determined according to the thickness, composition, moisture content, etc. of the separator 10. The content of the capsule can be a reaction raw material of a medicine or a cell-free protein synthesis system, and can also be any reactant needing to be mixed, such as nutritional ingredients.
alternatively, at least inwardly protruding projections 6 are provided on the inside of the outer capsule 1, which projections 6 will pierce the septum 10 during application of force, thereby allowing the contents of the different compartments to mix, and in particular, the projections 6 may be of any shape having a pointed tip, wherein the projections 6 are formed integrally with the capsule .
alternatively, the diaphragm 10 is supported by the outer capsule 1 by at least connecting portion 7, and during the application of force, the diaphragm 10 is pressed open and broken by the connecting portion 7, so that the contents in different compartments are mixed, and specifically, the connecting portion 7 is any shape that links the diaphragm and the outer capsule, and the connecting portion 7 can be disposed at any position.
alternatively, the septum 10 has a movable plug 8, the movable plug 8 can be disposed at any position on the septum 10, when an external force is applied, the movable plug 8 is pressed to separate from the septum, so as to mix the contents in different cavities, preferably, the movable plug 8 has a structure heads and heads, so as to be conveniently separated when the external force is applied.
alternatively, at least part of the diaphragm 10 is a frangible portion 9, wherein during the application of force, the frangible portion 9 is broken first by external pressure or pressure of the internal contents to mix the contents in different compartments, and the frangible portion 9 is a portion which is more fragile than other portions of the inner capsule and is easily broken.
alternatively, the two membranes may be filled with a gas other than the desired contents so that the degree of expansion within the compartment is close to the critical value of rupture, so that the membranes are susceptible to rupture when subjected to external forces, and the filling gas may be selected from any or combination of helium, neon, argon, krypton, xenon, nitrogen, oxygen, etc., which may help to stabilize the contents and provide a gas environment for the reaction, such as oxygen, when the contents to be mixed require certain gas conditions for reaction.
It should be noted that are optional for the means of breaking or opening, and any combination of the above means may be used.
Example 3
A method of using the capsule of embodiment 1 or 2, wherein the outer capsule is acted by external force to break or open the inner capsule or membrane, while the outer capsule is not broken, and the contents of each layer or each compartment are mixed or reacted in the outer capsule.
While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention.
Claims (20)
- The capsules comprise an outermost outer capsule, wherein at least inner capsules or at least diaphragms are contained in the outer capsule, and the outer capsule is characterized by having toughness, and when the outer capsule is subjected to external force, the inner capsules or the diaphragms are broken or opened while the outer capsule is kept unbroken.
- 2. The capsule according to claim 1, wherein: the outer capsules are dissolved and/or digested in vivo.
- 3. The capsule of claim 1, wherein the outer layer of the capsule is transparent or has viewing ports.
- 4. The capsule of claim 1, wherein the inner layer capsule is a collar-type layer-by-layer wrap, or at least inner layer capsules are fixed at any position inside the outer layer capsule, or at least two inner layer capsules are independent of each other and free inside the outer layer capsule.
- 5. The capsule of claim 1, wherein the inner capsule and the outer capsule are both body structures or the inner capsule and the outer capsule are both composed of split structures of capsule bodies and capsule caps or the inner capsule and the outer capsule are a combination of the body structure and the split structures.
- 6. The capsule according to claim 1, wherein: the inner layer capsule is composed of at least two different chambers.
- 7. The capsule according to any of claims 1-6, wherein the contents filled in the capsule are any combination of solution, suspension, solid, semi-solid, gas, emulsion, suspension, flowable powder, and granules.
- 8. The capsule according to any of of claims 1-6, wherein the inner capsule or membrane in direct contact with the contents of the outer capsule is not dissolved by the liquid or is hydrophobic when the liquid is carried in the outer capsule.
- 9. The capsule according to claim 8, wherein: the means that is not dissolved by the liquid or is hydrophobic is to apply or coat a protective coating.
- 10. The capsule of claim 9, wherein the protective coating is a natural oil, a synthetic oil, or a mixture thereof, wherein the natural oil is or more of vegetable oil, animal fat, and mineral oil.
- 11. The capsule of claim 9, wherein the protective coating is selected from the group consisting of emulsifiers, animal waxes, vegetable waxes, mineral oils, synthetic waxes, natural resins, and synthetic resins.
- 12. The capsule according to claim 8, wherein: the non-liquid soluble or hydrophobic means is that the inner capsule or membrane in direct contact with the contents of the outer capsule is composed of water insoluble ingredients.
- 13. The capsule according to any of claims 1-6, wherein the inner side of the inner capsule or the portion of the membrane is provided with protrusions, the protrusions are body structures of the inner capsule or the membrane, and the protrusions are in any shape with cusps.
- 14. The capsule according to claim 13, wherein: the inner side of the inner layer capsule or the corresponding position of the diaphragm is provided with a protruding bubble part corresponding to the protruding part.
- 15. The capsule of any one of claims 1 to 6 to , wherein at least the inner side of the outer capsule is provided with at least inwardly protruding lugs, which may be any shape having pointed tips.
- 16. The capsule according to any of claims 1-6 to , wherein the inner capsule or membrane is supported within the outer capsule by at least connecting portion, the connecting portion being any shape that connects the inner capsule or membrane to the outer capsule.
- 17. The capsule according to any of of claims 1-6, wherein the inner capsule or the membrane has a movable plug thereon.
- 18. The capsule of any one of claims 1 to 6 to , wherein at least the portion of the inner capsule or the membrane is a frangible portion.
- 19. The capsule according to any of claims 1-6, wherein the inner capsule or the membrane is filled with a gas in addition to the desired contents so that the degree of expansion of the compartment formed by the inner capsule or the membrane approaches the breakage threshold.
- 20, method for using the capsule, wherein the capsule is the capsule of any of claims 1-19, and the method is characterized in that, in use, the outer capsule is acted by external force, so that the inner capsule or the diaphragm is broken or opened, while the outer capsule is not broken, and the contents of the layers or the cavities are mixed or reacted in the outer capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810796311.1A CN110731949A (en) | 2018-07-19 | 2018-07-19 | capsules and application method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810796311.1A CN110731949A (en) | 2018-07-19 | 2018-07-19 | capsules and application method thereof |
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| CN110731949A true CN110731949A (en) | 2020-01-31 |
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| CN201810796311.1A Pending CN110731949A (en) | 2018-07-19 | 2018-07-19 | capsules and application method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111956625A (en) * | 2020-08-17 | 2020-11-20 | 江苏大地动物保健品有限公司 | An edible veterinary drug for livestock breeding for treating diarrhea |
| CN113789100A (en) * | 2021-07-19 | 2021-12-14 | 河南省路嘉路桥股份有限公司 | Waterproof material for concrete matrix and preparation method thereof |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1990002655A1 (en) * | 1988-09-06 | 1990-03-22 | Encapsulation Systems, Inc. | Realease assist microcapsules |
| WO1999059556A1 (en) * | 1998-05-15 | 1999-11-25 | Nasa/Johnson Space Center | Externally triggered microcapsules |
| CN2506254Y (en) * | 2001-11-12 | 2002-08-21 | 郑东阳 | Huweidan capsule |
| US20030150832A1 (en) * | 2000-07-20 | 2003-08-14 | Massoud Bakhshaee | Delivery device |
| CN2614676Y (en) * | 2003-04-25 | 2004-05-12 | 杨再福 | Capsules for multi-layer medicines |
| KR20050020195A (en) * | 2003-08-21 | 2005-03-04 | 안병옥 | Ginseng-hotpack |
| CN201186054Y (en) * | 2008-05-15 | 2009-01-28 | 王次霞 | Multi-layer structure capsules |
| CN101385892A (en) * | 2008-10-08 | 2009-03-18 | 陈东 | Stuffy nose with capsule |
| CN202568887U (en) * | 2012-04-18 | 2012-12-05 | 广西双蚁药业有限公司 | Structural improved capsule |
| CN104893827A (en) * | 2015-06-24 | 2015-09-09 | 云南中烟工业有限责任公司 | Preparation method of composite encapsulation capsules for cigarettes |
| CN205145144U (en) * | 2015-09-28 | 2016-04-13 | 浙江药联胶丸有限公司 | Modular capsule |
-
2018
- 2018-07-19 CN CN201810796311.1A patent/CN110731949A/en active Pending
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1990002655A1 (en) * | 1988-09-06 | 1990-03-22 | Encapsulation Systems, Inc. | Realease assist microcapsules |
| WO1999059556A1 (en) * | 1998-05-15 | 1999-11-25 | Nasa/Johnson Space Center | Externally triggered microcapsules |
| US20030150832A1 (en) * | 2000-07-20 | 2003-08-14 | Massoud Bakhshaee | Delivery device |
| CN2506254Y (en) * | 2001-11-12 | 2002-08-21 | 郑东阳 | Huweidan capsule |
| CN2614676Y (en) * | 2003-04-25 | 2004-05-12 | 杨再福 | Capsules for multi-layer medicines |
| KR20050020195A (en) * | 2003-08-21 | 2005-03-04 | 안병옥 | Ginseng-hotpack |
| CN201186054Y (en) * | 2008-05-15 | 2009-01-28 | 王次霞 | Multi-layer structure capsules |
| CN101385892A (en) * | 2008-10-08 | 2009-03-18 | 陈东 | Stuffy nose with capsule |
| CN202568887U (en) * | 2012-04-18 | 2012-12-05 | 广西双蚁药业有限公司 | Structural improved capsule |
| CN104893827A (en) * | 2015-06-24 | 2015-09-09 | 云南中烟工业有限责任公司 | Preparation method of composite encapsulation capsules for cigarettes |
| CN205145144U (en) * | 2015-09-28 | 2016-04-13 | 浙江药联胶丸有限公司 | Modular capsule |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111956625A (en) * | 2020-08-17 | 2020-11-20 | 江苏大地动物保健品有限公司 | An edible veterinary drug for livestock breeding for treating diarrhea |
| CN113789100A (en) * | 2021-07-19 | 2021-12-14 | 河南省路嘉路桥股份有限公司 | Waterproof material for concrete matrix and preparation method thereof |
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