CN105963282B - A kind of medical metered dose inhalation aerosol - Google Patents
A kind of medical metered dose inhalation aerosol Download PDFInfo
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- CN105963282B CN105963282B CN201610288344.6A CN201610288344A CN105963282B CN 105963282 B CN105963282 B CN 105963282B CN 201610288344 A CN201610288344 A CN 201610288344A CN 105963282 B CN105963282 B CN 105963282B
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- metered dose
- tank
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- medical
- dose inhalation
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- 239000000443 aerosol Substances 0.000 title claims abstract description 62
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052782 aluminium Inorganic materials 0.000 claims abstract description 29
- NDAUXUAQIAJITI-LBPRGKRZSA-N (R)-salbutamol Chemical compound CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-LBPRGKRZSA-N 0.000 claims abstract description 28
- 229950008204 levosalbutamol Drugs 0.000 claims abstract description 28
- 239000004411 aluminium Substances 0.000 claims abstract description 27
- 238000002360 preparation method Methods 0.000 claims abstract description 27
- 239000000470 constituent Substances 0.000 claims abstract description 19
- 239000003380 propellant Substances 0.000 claims abstract description 13
- 208000006673 asthma Diseases 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 235000019441 ethanol Nutrition 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 239000004094 surface-active agent Substances 0.000 claims description 5
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 3
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 3
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 3
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000005642 Oleic acid Substances 0.000 claims description 3
- 239000006184 cosolvent Substances 0.000 claims description 3
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 3
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 230000003014 reinforcing effect Effects 0.000 claims description 2
- 229910001051 Magnalium Inorganic materials 0.000 claims 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims 1
- 239000010931 gold Substances 0.000 claims 1
- 229910052737 gold Inorganic materials 0.000 claims 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 claims 1
- 229960003132 halothane Drugs 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 13
- -1 ether compound Chemical class 0.000 abstract description 9
- 230000000144 pharmacologic effect Effects 0.000 abstract description 6
- 239000012535 impurity Substances 0.000 description 14
- 239000003814 drug Substances 0.000 description 9
- 238000007789 sealing Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 4
- 229910000861 Mg alloy Inorganic materials 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000000857 drug effect Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- NWGKJDSIEKMTRX-MDZDMXLPSA-N Sorbitan oleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)C1OCC(O)C1O NWGKJDSIEKMTRX-MDZDMXLPSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 150000005828 hydrofluoroalkanes Chemical group 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229910000838 Al alloy Inorganic materials 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical group [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229960002052 salbutamol Drugs 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 125000005909 ethyl alcohol group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010829 isocratic elution Methods 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000003405 preventing effect Effects 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005028 tinplate Substances 0.000 description 1
Classifications
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
- A61K9/124—Aerosols; Foams characterised by the propellant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0001—Details of inhalators; Constructional features thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/0063—Storages for pre-packed dosages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0065—Inhalators with dosage or measuring devices
- A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0086—Inhalation chambers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/10—Trunk
- A61M2210/1025—Respiratory system
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Anesthesiology (AREA)
- Biophysics (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of medical metered dose inhalation aerosols, pressurised metered dose inhalers including aerosol preparation and for containing said preparation, the aerosol preparation includes the active constituent and liquefied propellant for treating asthma, the pressurised metered dose inhalers include container tank, metering valve and driver, and the container tank is aluminium pot.Container tank of the present invention by using aluminium pot as aerosol, avoids the generation of ether compound in aerosol, it is ensured that the pharmacological property of active constituent Levalbuterol and human body it is healthy and safe.
Description
Technical field
The present invention relates to treatment asthma aerosol products technical fields, and in particular to a kind of medical metered dose inhalation aerosol.
Background technique
Aerosol generally comprises aerosol preparation and the pressurised metered device for containing said preparation.Currently, pressurised metered suction
Entering device (MDIs) is human airway low dose is accurately administered most effective and most can received mode.Typical MDIs packet
The anti-autoclave that therapeutic agent is housed is included, wherein therapeutic agent is mostly and is dissolved in the drug of liquefied propellant or is suspended in liquefaction to throw
The micronized drug particles in agent are penetrated, are additionally provided with metering valve on MDIs, by touching metering valve to discharge a certain amount for the treatment of
Agent.
Currently, the dissolving of pressurised metered dose inhalers (MDIs), using wiredrawn edge can, wiredrawn edge can is adopted
It is prepared with extrusion molding process, containing about in the active constituent Levalbuterol product for treating asthma used both at home and abroad
5% ethyl alcohol.
The aerosol preparation in aerosol is easily led to using pressurised metered dose inhalers made of wiredrawn edge can to contain greatly
The ether compound of amount, the presence of ether compound not only influence whether the pharmacological property of aerosol preparation active constituent, but also can shadow
It rings and arrives human health.
Summary of the invention
The purpose of the present invention is to provide a kind of medical metered dose inhalation aerosols, solve the aerosol system in existing aerosol
Agent contains the problem of a large amount of ether compound, to improve the pharmacological property of active constituent in aerosol preparation and improve aerosol
Safety.
The present invention is achieved through the following technical solutions:
A kind of medical metered dose inhalation aerosol, the pressurised metered sucking including aerosol preparation and for containing said preparation
Device, the aerosol preparation include the active constituent and liquefied propellant for treating asthma, the pressurised metered dose inhalers packet
Container tank, metering valve and driver are included, the container tank is aluminium pot.
In the prior art, in order to ensure the hardness of container tank, shape distortion is avoided, generallys use wiredrawn edge can,
Wiredrawn edge can specifically refers to a kind of using tank body made of tinplate, and the filling mouth of tank body is wiredrawn edge structure, wiredrawn edge structure tool
Body refers to structure made of the axial end portion of tubular body turns down outward.Contain micro heavy ion in wiredrawn edge can, such as
It is chromium, nickel, violent；And the active constituent of the treatment asthma in aerosol is Levalbuterol, contains ethyl alcohol in Levalbuterol,
The structural formula of Levalbuterol are as follows:Levalbuterol and ethyl alcohol exist
Ether degradation reaction occurs under the catalytic action of heavy metal ion and generates ether compound, that is, impurity A and impurity B, reaction equation is such as
Under:
Ether compound is the substance being harmful to the human body, and the presence of ether compound not only influences whether active constituent Levalbuterol
Pharmacological property, and the health of human body is influenced whether after being absorbed by the body together with active constituent.
Container tank of the present invention is aluminium pot, and aluminium pot is specifically referred to using tank body made of aluminum material, and aluminum material is existing
Technologic material will not usually be used as the container tank of aerosol, the present invention is in use since aluminium material is soft in this field
In order to overcome the problems, such as that aluminium material is soft, the outer wall of aluminium pot can be provided with reinforcing rib or be arranged the higher shell of hardness, by
Without the heavy metal ion such as chromium, nickel, violent in aluminium pot, and then lack Levalbuterol and second in aerosol of the present invention
The catalyst of ether degradation reaction occurs for alcohol, and then Levalbuterol will not react with ethyl alcohol, it is ensured that institute of the present invention
Ether compound will not be generated in the aerosol stated, it is ensured that the pharmacological property of active constituent Levalbuterol and the health peace of human body
Entirely.
Further, container tank includes tank body and Guan Kou, and the tank mouth is notch, and the tank mouth includes seal groove, locking
Slot and stop collar, seal groove, locking slot and stop collar are sequentially connected with from top to bottom.
Existing container tank is wiredrawn edge can, and the pressurised metered dose inhalers are arranged in container tank, metering valve
Sealing between the filling mouth of container tank is realized by setting gasket, since the filling mouth of existing wiredrawn edge can is light
Sliding planar structure, in use, the drive rod in pressurised metered dose inhalers move back and forth under the action of driver,
A thrust can be applied in moving process to gasket, gasket be subjected to displacement under the action of thrust or even fall off and metering valve
Between the filling mouth of container tank, and then the leakproofness of metering valve and container tank filled between mouth is caused to reduce, leakproofness reduces by one
Aspect will lead to liquefied propellant and leak under condition of storage, so that always pressing time decline, liquor strength be caused to increase,
The homogeneity for causing delivering to be measured is unqualified, on the other hand also results in more moisture and enters medical fluid, moisture penetrates into mixed
It can adhere to surface of drug particles after outstanding type MDI to cause aggregation between drug granule and cause particle in valve and tank
Absorption on wall.
The port surface that notch of the present invention specifically refers to fill mouth is plane, described to be specifically referred to from top to bottom by filling mouth
To tank body, the seal groove specifically refers to a kind of groove structure for fixing seal pad, and the locking slot specifically refers to one kind
The structure filled between mouth that gasket is fixed on to metering valve and container tank is further realized, the stop collar specifically refers to one kind
The structure to glide for baffle seal pad.
Gasket is further fixed on metering valve and container tank by seal groove clamping gasket of the present invention, locking slot
Filling mouth between and stop collar baffle seal pad glide, being realized by the mutual cooperation of seal groove, locking slot and stop collar will
Gasket is firmly fixed between metering valve and the filling mouth of container tank, and be will not be subjected to displacement under the action of thrust, more
It will not fall off, it is ensured that the leakproofness of aerosol, and then improve the stability of drug effect.
Further, the internal diameter of locking slot is in the trend being gradually reduced from bottom to top；The stop collar is tank body and locking
The inwardly protruded structure in slot junction；The seal groove be annular groove, seal groove it is interior connect without leave with locking slot it is end-to-end
Mouth presents and is gradually increased the trend being gradually reduced again.
Specifically, the maximum inner diameter of locking slot of the present invention is more than or equal to the internal diameter of tank body；The seal groove uses
Gasket can be preferably clamped in seal groove by above structure, can avoid to a certain extent gasket on move down
It is dynamic, improve the fixed effect of gasket；The protrusion further avoids moving down for gasket, and the locking slot is using the above structure
Also gasket can be avoided to glide to a certain extent, further increases clamping effect of the gasket in seal groove.
Further, the neonychium that mouth cooperation is filled with container tank is provided on the outer wall of the metering valve.
The neonychium specifically refers to the annular that container tank filling mouth end is gradually increased to metering valve outer end without leave outside one kind
Bulge-structure, the metering valve outer end specifically refer to one end that metering valve is arranged in outside container tank, and the present invention passes through setting
Neonychium, on the one hand can further prevent gasket to move up, and on the other hand can be avoided metering valve and fall completely within container
In tank.
Further, aluminium pot is made of magnesium alloy；The aluminium pot uses deep draw continuous forming process.
The magnesium alloy is the prior art, in particular to magnesium ion is added in aluminium alloy, improves the hardness of aluminium alloy,
And then improve the structural stability of aluminium pot.
The structural stability of magnesium alloy can be further increased using deep draw continuous forming process.
Further, active constituent is Levalbuterol and its salt；The Levalbuterol is in aerosol preparation
Content be 0.01-0.5wt%.
The drug effect of the Levalbuterol is 80 times of dextrorotation salbutamol, and the absorptivity of Levalbuterol is than the right side
It is high to revolve salbutamol；Levalbuterol has better curative effect, and has the advantages that Small side effects, dosage are small.
Currently, standard content of the Levalbuterol in aerosol is 0.065-0.33wt%, it is comprehensive in use process
In do not press medicament contg allow fluctuation 30%, in fluctuation range, applicant it is proved by many experiments that, in Levalbuterol
Content in aerosol preparation is that 0.01-0.5wt% has preferable drug effect and preservation effect.
Further, aerosol preparation is medical suspension type aerosol.
Further, liquefied propellant is hydrofluoroalkane or hydrofluorocarbon.
Chlorofluorocarbons is used in traditional aerosol formulations, to ozone layer after being discharged into atmospheric environment
It destroys larger, is unfavorable for environmental protection.
Hydrofluoroalkane of the present invention or hydrofluorocarbon are smaller to the destruction of ozone layer, are conducive to environmental protection.
Further, hydrofluorocarbon is the mixture of HFA 134a or HFA 227 or both.
Further, the mixture in liquefied propellant also containing cosolvent or surfactant or both, the hydrotropy
Agent is ethyl alcohol, and the surfactant is the mixture of one or more of oleic acid, sorbester p17, phosphatide.
Ethyl alcohol can help drug dispersion to play the role of suspending in Levalbuterol aerosol；The surface-active
Agent can reduce the surface tension of suspension aerosol drug microparticles, increase the physical stability of preparation.
Compared with prior art, the present invention having the following advantages and benefits:
1, container tank of the present invention by using aluminium pot as aerosol, avoids the life of ether compound in aerosol
At, it is ensured that active constituent Levalbuterol pharmacological property and human body it is healthy and safe.
2, the filling mouth of the container tank in aerosol of the present invention is notch features, fills mouth and is provided with mutual cooperation for card
Seal groove, locking slot and the stop collar of close packing, it is ensured that gasket be firmly clamped on metering valve and container tank filling mouth it
Between, and then improve the leakproofness of metering valve and container tank filled between mouth, can have the effective leakage for reducing liquefied propellant,
Moisture enters medical fluid, advantageously ensure that product in aerosol storage process Ou Nuo quality stability.
3, aerosol of the present invention is small to the destruction of ozone layer, is conducive to environmental protection.
Detailed description of the invention
Attached drawing described herein is used to provide to further understand the embodiment of the present invention, constitutes one of the application
Point, do not constitute the restriction to the embodiment of the present invention.In the accompanying drawings:
Fig. 1 is the structural schematic diagram of aerosol；
Fig. 2 is the structural schematic diagram of container tank；
Fig. 3 is the structural schematic diagram of metering valve.
Label and corresponding parts title in attached drawing:
1- container tank, 2- metering valve, 3- driver, 4- gasket, 5- neonychium, 11- tank body, 21- valve body, 22- spring,
23- sealing ring, 24- drive rod, 121- seal groove, 122- locking slot, 123- stop collar.
Specific embodiment
To make the objectives, technical solutions, and advantages of the present invention clearer, below with reference to embodiment and attached drawing, to this
Invention is described in further detail, and exemplary embodiment of the invention and its explanation for explaining only the invention, are not made
For limitation of the invention.
Embodiment 1:
As shown in Figure 1, Figure 3, a kind of medical metered dose inhalation aerosol, including aerosol preparation and for containing said preparation
Pressurised metered dose inhalers, the aerosol preparation include the active constituent and liquefied propellant for treating asthma, the pressurization
Metered dose inhaler includes container tank 1, metering valve 2 and driver 3, and the container tank 1 is aluminium pot.
Specifically, the metering valve 2 includes valve body 21, is provided with spring 22 and sealing ring 23, sealing ring 23 in valve body 21
On be connected with drive rod 24 for braking sealing circle 23, drive rod 24 is connected with driver 3, in terms of through the braking of driver 3
It measures valve 2 and realizes dosed administration, suction side, outlet side and the measurement chamber of metering valve 2 are arranged in the cavity of valve body 21.
The present invention, as container tank 1, avoids active constituent Levalbuterol and ethyl alcohol in a huge sum of money by using aluminium pot
Etherization reaction occurs under the catalytic action of category, improves drug effect.
Embodiment 2:
For figure such as 1 to shown in Fig. 3, the present embodiment is based on embodiment 1, and the container tank 1 includes tank body 11 and Guan Kou, the tank
Mouth is notch, and the tank mouth includes seal groove 121, locking slot 122 and stop collar 123, seal groove 121, locking slot 122 and limit
Ring 123 is sequentially connected with from top to bottom；The internal diameter of the locking slot 122 is in the trend being gradually reduced from bottom to top；The stop collar
123 be tank body 11 and the inwardly protruded structure in 122 junction of locking slot；The seal groove 121 is annular groove, seal groove 121
Interior the trend for being gradually increased and being gradually reduced again is presented to port with 122 connecting pin of locking slot without leave；The locking slot 122 is most
Large diameter is more than or equal to the internal diameter of tank body 11.
Using container tank 1 described in the present embodiment, it is ensured that gasket 4 is firmly clamped on seal groove 121, realizes container
Tank 1 fills the sealing between mouth and metering valve 2, improves sealing effect.
Embodiment 3:
The present embodiment is based on embodiment 2, and the protection that mouth cooperation is filled with container tank 1 is provided on the outer wall of the metering valve 2
Pad 5.
Embodiment 4:
The present embodiment is based on embodiment 1, and the aluminium pot is made of magnesium alloy；The aluminium pot using deep draw continuously at
Type technique.
Embodiment 5:
The present embodiment is based on embodiment 1, and the active constituent is Levalbuterol and its salt；The Levalbuterol
Content in aerosol preparation is 0.11wt%；The aerosol preparation is medical suspension type aerosol；The liquefaction is thrown
Penetrating agent is hydrofluoroalkane or hydrofluorocarbon；The hydrofluorocarbon specifically selects HFA 134a, be also possible to HFA 227 or HFA 134a and
The mixture of HFA 227；Also contain ethyl alcohol in the liquefied propellant, ethyl alcohol and oleic acid or ethyl alcohol and sorbester p17 can also be contained
Or phosphatide or sorbester p17 and phosphatide.
Embodiment 6:
The present embodiment is based on embodiment 5, and content of the Levalbuterol in embodiment 5 in aerosol preparation is replaced
At 0.01wt%.
Embodiment 7:
The present embodiment is based on embodiment 5, and content of the Levalbuterol in embodiment 5 in aerosol preparation is replaced
At 0.5wt%.
Compare the catabolite and leak preventing effect of notch aluminium pot and wiredrawn edge can using comparative test.
Following comparative testing uses high performance liquid chromatography (HPLC) catabolite condition are as follows:
Chromatographic column: Phenomenex Gemini C18 110A；
Mobile phase A: 0.08mol/L sodium dihydrogen phosphate buffer, pH3.1；
Mobile phase B: methanol；
Mobile phase A: Mobile phase B=93:7 (volume/volume), isocratic elution；
Column temperature: 30 DEG C；
Sample volume: 50 μ L；
Flow velocity: 1.0mL/min；
Detection wavelength: 225nm；
Runing time: 35min.
Medical fluid moisture content is measured using ten thousand logical coulombs of moisture tellers:
Prescription containing ethyl alcohol and liquefied propellant HFA 134a carries out accelerated test 2 in 40 DEG C under the conditions of RH=75%de
A month, set two formulas: as shown in table 1, formula two is as shown in table 2 for formula one:
Table 1
| Component | Weight | Shared weight fraction |
| Levalbuterol | 17.40mg | 0.11% |
| Ethyl alcohol | 0.5g | 5.0% |
| HFA134a | 9.5g | 94.89% |
Table 2
| Component | Weight | Shared weight fraction |
| Levalbuterol | 17.40mg | 0.11% |
| Ethyl alcohol | 1.0g | 10.0% |
| HFA134a | 9.0g | 89.89% |
Extract is detected using HPLC, the testing result of wiredrawn edge can extract is as shown in table 3, table 4, wherein W/W
For weight ratio.
Table 3
Table 4
The testing result of notch aluminium pot extract is as shown in table 5, table 6:
Table 5
Table 6
It is compared by the experimental data of table 3 and table 5, table 4 and table 6 are experimental data comparisons, are concluded that
Notch aluminium pot is compared with wiredrawn edge horse mouthful tank:
In formula one: the content of impurities of first month reduces 37%.The content of impurities of second month reduces
40%, the slip of first month reduces 41%, and the slip of second month reduces 50%.
In formula two: the content of impurities of first month reduces 47%.The content of impurities of second month reduces
56%, the slip of first month reduces 60%, and the slip of second month reduces 57%.
I.e. the present invention is by the way that by container tank 1, by being made of notch aluminium pot, impurity content is significantly reduced, and slip is also bright
It is aobvious to reduce.
When the content of active constituent in formula is 0.01, notch aluminium pot is compared with wiredrawn edge horse mouthful tank:
In formula one: the content of impurities of first month reduces 36%.The content of impurities of second month reduces
4%, the slip of first month reduces 38%, and the slip of second month reduces 45%.
In formula two: the content of impurities of first month reduces 40%.The content of impurities of second month reduces
50%, the slip of first month reduces 48%, and the slip of second month reduces 52%.
When the content of active constituent in formula is 0.5wt%, notch aluminium pot is compared with wiredrawn edge horse mouthful tank:
In formula one: the content of impurities of first month reduces 43%.The content of impurities of second month reduces
47%, the slip of first month reduces 44%, and the slip of second month reduces 54%.
In formula two: the content of impurities of first month reduces 51%.The content of impurities of second month reduces
59%, the slip of first month reduces 57%, and the slip of second month reduces 60%.
Above-described specific embodiment has carried out further the purpose of the present invention, technical scheme and beneficial effects
It is described in detail, it should be understood that being not intended to limit the present invention the foregoing is merely a specific embodiment of the invention
Protection scope, all within the spirits and principles of the present invention, any modification, equivalent substitution, improvement and etc. done should all include
Within protection scope of the present invention.
Claims (8)
1. a kind of medical metered dose inhalation aerosol, the pressurised metered dose inhalers including aerosol preparation and for containing said preparation,
The aerosol preparation includes the active constituent and liquefied propellant for treating asthma, and the pressurised metered dose inhalers include holding
Device tank (1), metering valve (2) and driver (3), which is characterized in that the container tank (1) is aluminium pot；The container tank (1) includes
Tank body (11) and tank mouth, the tank mouth are notch, and the tank mouth includes seal groove (121), locking slot (122) and stop collar
(123), seal groove (121), locking slot (122) and stop collar (123) are sequentially connected with from top to bottom；The tank of the container tank (1)
It is provided with gasket (4) between mouth and metering valve (2), described gasket (4) one end is clamped in seal groove (121)；The lock
The internal diameter of tight slot (122) is in the trend being gradually reduced from bottom to top；The stop collar (123) is tank body (11) and locking slot
(122) the inwardly protruded structure in junction；The seal groove (121) be annular groove, seal groove (121) it is interior without leave with locking
The trend for being gradually increased and being gradually reduced again is presented to port for slot (122) connecting pin；The active constituent be Levalbuterol and
Its salt；The outer wall of the aluminium pot (1) is provided with reinforcing rib.
2. a kind of medical metered dose inhalation aerosol according to claim 1, which is characterized in that outside the metering valve (2)
The neonychium (5) with the cooperation of container tank (1) tank mouth is provided on wall.
3. a kind of medical metered dose inhalation aerosol according to claim 1, which is characterized in that the aluminium pot is closed using magnalium
Gold is made；The aluminium pot uses deep draw continuous forming process.
4. a kind of medical metered dose inhalation aerosol according to claim 1, which is characterized in that the Levalbuterol exists
Content in aerosol preparation is 0.01-0.5wt%.
5. a kind of medical metered dose inhalation aerosol according to claim 1, which is characterized in that the aerosol preparation is doctor
With suspension type aerosol.
6. a kind of medical metered dose inhalation aerosol according to claim 1, which is characterized in that the liquefied propellant is hydrogen
Fluothane or hydrofluorocarbon.
7. a kind of medical metered dose inhalation aerosol according to claim 6, which is characterized in that the hydrofluorocarbon is HFA
The mixture of 134a or HFA 227 or both.
8. a kind of medical metered dose inhalation aerosol according to claim 1, which is characterized in that in the liquefied propellant also
Mixture containing cosolvent or surfactant or both, the cosolvent are ethyl alcohol, and the surfactant is oleic acid, department
The mixture of one or more of disk 80, phosphatide.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101849928A (en) * | 2009-03-30 | 2010-10-06 | 北京利乐生制药科技有限公司 | Inhalation preparation for treating asthma, preparation method and application thereof |
| CN102573791A (en) * | 2009-10-16 | 2012-07-11 | 雅戈泰克股份公司 | Improved formulations |
| CN104225739A (en) * | 2014-09-30 | 2014-12-24 | 四川普锐特医药科技有限责任公司 | Medical quantitative inhalation aerosol |
| CN104661931A (en) * | 2012-09-20 | 2015-05-27 | 普莱斯博有限两合公司 | Canister for a metered dose inhaler and method of manufacturing such a canister |
-
2016
- 2016-05-04 CN CN201610288344.6A patent/CN105963282B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101849928A (en) * | 2009-03-30 | 2010-10-06 | 北京利乐生制药科技有限公司 | Inhalation preparation for treating asthma, preparation method and application thereof |
| CN102573791A (en) * | 2009-10-16 | 2012-07-11 | 雅戈泰克股份公司 | Improved formulations |
| CN104661931A (en) * | 2012-09-20 | 2015-05-27 | 普莱斯博有限两合公司 | Canister for a metered dose inhaler and method of manufacturing such a canister |
| CN104225739A (en) * | 2014-09-30 | 2014-12-24 | 四川普锐特医药科技有限责任公司 | Medical quantitative inhalation aerosol |
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