CN106619658A - Medical aerosol preparation and quantitatively-inhaled aerosol - Google Patents
Medical aerosol preparation and quantitatively-inhaled aerosol Download PDFInfo
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- CN106619658A CN106619658A CN201611236776.9A CN201611236776A CN106619658A CN 106619658 A CN106619658 A CN 106619658A CN 201611236776 A CN201611236776 A CN 201611236776A CN 106619658 A CN106619658 A CN 106619658A
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- aerosol
- medical
- span
- metered dose
- preparation
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- 239000000443 aerosol Substances 0.000 title claims abstract description 95
- 238000002360 preparation method Methods 0.000 title claims abstract description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000003380 propellant Substances 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 32
- NWGKJDSIEKMTRX-MDZDMXLPSA-N Sorbitan oleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)C1OCC(O)C1O NWGKJDSIEKMTRX-MDZDMXLPSA-N 0.000 claims description 25
- 239000002245 particle Substances 0.000 claims description 19
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 18
- 238000009472 formulation Methods 0.000 claims description 18
- 229920000642 polymer Polymers 0.000 claims description 14
- 238000000576 coating method Methods 0.000 claims description 12
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 12
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 12
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 claims description 11
- 239000011248 coating agent Substances 0.000 claims description 10
- 239000001530 fumaric acid Substances 0.000 claims description 9
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 7
- 239000003595 mist 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 3
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 claims description 3
- 238000007334 copolymerization reaction Methods 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 17
- 239000004094 surface-active agent Substances 0.000 abstract description 7
- OBRNDARFFFHCGE-PERKLWIXSA-N (S,S)-formoterol fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1=CC(OC)=CC=C1C[C@H](C)NC[C@@H](O)C1=CC=C(O)C(NC=O)=C1.C1=CC(OC)=CC=C1C[C@H](C)NC[C@@H](O)C1=CC=C(O)C(NC=O)=C1 OBRNDARFFFHCGE-PERKLWIXSA-N 0.000 abstract description 6
- 229960000193 formoterol fumarate Drugs 0.000 abstract description 6
- 239000010419 fine particle Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 abstract 7
- 235000019441 ethanol Nutrition 0.000 abstract 1
- 230000001050 lubricating effect Effects 0.000 abstract 1
- 229960002744 mometasone furoate Drugs 0.000 abstract 1
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 abstract 1
- 239000000725 suspension Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 32
- 239000003795 chemical substances by application Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 5
- 239000005642 Oleic acid Substances 0.000 description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 4
- 238000000280 densification Methods 0.000 description 4
- 238000005461 lubrication Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 3
- 230000001133 acceleration Effects 0.000 description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 description 3
- 210000003123 bronchiole Anatomy 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000008249 pharmaceutical aerosol Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 229910000838 Al alloy Inorganic materials 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000000621 bronchi Anatomy 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000010422 painting Methods 0.000 description 2
- 235000010603 pastilles Nutrition 0.000 description 2
- BLUGYPPOFIHFJS-UUFHNPECSA-N (2s)-n-[(2s)-1-[[(3r,4s,5s)-3-methoxy-1-[(2s)-2-[(1r,2r)-1-methoxy-2-methyl-3-oxo-3-[[(1s)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 BLUGYPPOFIHFJS-UUFHNPECSA-N 0.000 description 1
- JRHNUZCXXOTJCA-UHFFFAOYSA-N 1-fluoropropane Chemical compound CCCF JRHNUZCXXOTJCA-UHFFFAOYSA-N 0.000 description 1
- 208000007934 ACTH-independent macronodular adrenal hyperplasia Diseases 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- REDXJYDRNCIFBQ-UHFFFAOYSA-N aluminium(3+) Chemical compound [Al+3] REDXJYDRNCIFBQ-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229940124748 beta 2 agonist Drugs 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- UKACHOXRXFQJFN-UHFFFAOYSA-N heptafluoropropane Chemical group FC(F)C(F)(F)C(F)(F)F UKACHOXRXFQJFN-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- -1 polytetrafluoroethylene Polymers 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a medical aerosol preparation and quantitatively-inhaled aerosol. The preparation comprises active components and a liquid propellant which is used as a solvent of the active components, wherein the active components comprise mometasone furoate and formoterol fumarate; the liquid propellant is hydrofluorocarbon; the medical aerosol preparation also comprises ethyl alcohol and span-80 which are added into the liquid propellant; the weight ratio of the span-80 in the aerosol preparation is 0.01-0.1%w/w; medical liquid in the aerosol is the medical aerosol preparation. According to the scheme, span-80 is added into the aerosol preparation and is used as a surfactant; span-80 is capable of maintaining uniform concentration of the medical liquid for a long time, so that the purpose of improving the stability of the medical liquid is achieved; the addition amount of span-80 is limited, so that the influence on generation of the medical aerosol and reduction of dosage of fine particles caused by excessive span-80 can be avoided when span-80 achieves the effects of assisting suspension and lubricating.
Description
Technical field
The present invention relates to medicinal aerosol products field, more particularly to a kind of medicinal aerosol formulation and gas is quantitatively sucked
Mist agent.
Background technology
At present, pressurised metered dose inhalers (MDIs) are the most effective of administration low dose of accurate to human airway and most can quilt
The mode of acceptance.The general therapeutic agent for delivering by this way includes the bronchodilator of the adrenaline excitants of β 2, especially
It is β2agonists and hydrocortisone and combinations thereof.Typical MDIs includes an anti-autoclave equipped with therapeutic agent, wherein controlling
Treat agent to be mostly dissolved in the medicine of liquefied propellant or be suspended in micronized particle in liquefied propellant, meter is additionally provided with MDIs
Amount valve, by touching metering valve to discharge a certain amount of therapeutic agent.
Dissection and physiological make-up according to bronchus bronchiole and lung, to make medicine effectively be distributed or being deposited on
Above-mentioned position, it is desired to which the granularity of medicine or pastille droplet is in 5 microns.Excessive (10 microns of ＞'s) or too small (1 micron of ＜)
Granularity can not make drug deposition at above-mentioned position, and lessen the curative effect.So inhaling people's aerosol for medicine or pastille droplet
Granularity typically requires control at 10 microns, and wherein great majority should be less than 5 microns.Drug microparticles are respectively provided with larger at 5 microns
Surface energy, is readily adsorbed in vessel surface, so that liquid drug concentration is reduced, affects pharmaceutical effectiveness.
Describe in CN1196478 using the aerosol containing momestasone furoate and the pharmaceutical composition of formoterol fumarate
Treat obstructive or airway inflammatory disease.
It is 1 that CN101856362 specifically describes momestasone furoate and the weight ratio of formoterol fumarate:1 to 50:1, throw
It is HFA-227e to penetrate agent, while adding ethanol to adjust propellant output pressure, adds oleic acid to play dispersion medicine for surfactant
The effect of thing and lubrication valve.
Because fumaric acid good fortune model sieve is slightly soluble in ethanol, after long-time is placed, diameter of aspirin particle can be assembled, and cause liquor strength
It is uneven, so as to affect medicine delivery dose uniformity.How described above medicine delivery dose uniformity is solved the problems, such as,
It is those skilled in the art's technical problem urgently to be resolved hurrily.
The content of the invention
For being slightly soluble in ethanol because of fumaric acid good fortune model sieve in above-mentioned prior art, after long-time is placed, diameter of aspirin particle
Can assemble, cause liquor strength uneven, so as to affect the problem of medicine delivery dose uniformity.The invention provides a kind of doctor
With aerosol preparations and metered dose inhalation aerosol, the medicinal aerosol formulation remains able to effectively guarantor after storage certain hour
Demonstrate,prove its interior minuteness particle dosage, it is ensured that dosage delivered homogeneity.
To solve the above problems, a kind of medicinal aerosol formulation and metered dose inhalation aerosol that the present invention is provided passes through following
Technical essential carrys out solve problem：A kind of medicinal aerosol formulation, including active component and the liquid as the active component solvent
Change propellant, the active component includes momestasone furoate and fumaric acid good fortune model sieve, and the liquefied propellant is HFC, also
Including the ethanol and sorbester p17 that make an addition in liquefied propellant, weight ratio of the sorbester p17 shared by aerosol preparations is
0.01%-0.1%w/w.
Specifically, for the problem of above-mentioned influence of ethanol medicine delivery dose uniformity, to aerosol system in prior art
Add oleic acid in agent, but with the lengthening of aerosol preparations standing time, medicine delivery dose uniformity is gradually deteriorated.
In this programme, it is used as surfactant by adding sorbester p17 in aerosol preparations, when the sorbester p17 can be long
Between keep liquor strength uniform, so as to reach the purpose for increasing liquid medicine stability.Above to the restriction of sorbester p17 addition, it is intended to
While so that sorbester p17 plays suspending and lubrication, being unlikely to content excessively affects the generation of pharmaceutical aerosol, reduces
Fine particle dosage.
It is to cause in aerosol preparations as a kind of further technical scheme of above-described medicinal aerosol formulation
Active ingredient effectively branch or can be deposited in the bronchus of human body, bronchiole and lung, the momestasone furoate and
Fumaric acid good fortune model sieve is micro mist of the median particle diameter obtained Jing after air-flow crushing less than 5 microns.In this programme, due in gas
A certain amount of sorbester p17 is with the addition of in sol preparation, although the active ingredient of above median particle diameter has larger surface energy, but
It is still to be difficult to adsorb on vessel surface.
Used as a kind of liquefied propellant implementation beneficial to environmental protection, the HFC is HFA 134a, HFA 227
The mixture of any one in both or both.
Meanwhile, the invention also discloses a kind of medical metered dose inhalation aerosol, including medicinal aerosol formulation and for containing
The pressurised metered dose inhalers of dress said preparation, the medicinal aerosol formulation that the preparation is provided for one scheme of any of the above.
Above aerosol has used the aerosol preparations that as above any one scheme is provided, due to the aerosol preparations
Property, so, this aerosol products can be caused for a long time to keep liquor strength uniform, keep this aerosol so as to reach
The purpose of agent properties of product stability.
Used as the further technical scheme of the medical metered dose inhalation aerosol of one of the above, the pressurised metered dose inhalers include
Accommodating tank, metering valve and driver, the material of the accommodating tank is magnadure, houses inside tank partially or fully wall coated lining
There is perfluoroparaffin high polymer.
More than accommodating tank as aerosol preparations storage container, due to common surface of magnesium aluminium alloy natural oxide film both
Thin and soft, low density, surface irregularity easily adsorbs the particulate in medicine, while magnesium, the aluminium element of accommodating tank superficial layer
It is into the liquid etc. oozing.In this programme, by accommodating top tank structure partially or fully coated lining perfluoroparaffin high polymer, so, coated lining
Position can form the coating of one layer of densification, while the coating surface densification is smooth, be difficult to adsorb drug particles, it is to avoid gas is molten
Glue preparation and accommodating tank body contacts, so, in storing process, drug particles therein are not only difficult to be inhaled aerosol preparations
It is attached, while aerosol preparations will not also be subject to polluting for the metal ion for discharging, so, can effectively ensure that aerosol preparations performance
Stability.
Preferably, it is to reduce impact of the magnadure to aerosol preparations composition as far as possible, the accommodating tank inside is all
Wall is applied and is lined with perfluoroparaffin high polymer.
Preferably, as the specific implementation of the perfluoroparaffin high polymer, the perfluoroparaffin high polymer is following material
In one kind：PTFE, PEP, PFA, by PTFE, PEP, PFA three in the copolymer that arbitrarily both or three are formed.
The invention has the advantages that：
In this programme, it is used as surfactant by adding sorbester p17 in aerosol preparations, when the sorbester p17 can be long
Between keep liquor strength uniform, so as to reach the purpose for increasing liquid medicine stability.Above to the restriction of sorbester p17 addition, it is intended to
While so that sorbester p17 plays suspending and lubrication, being unlikely to content excessively affects the generation of pharmaceutical aerosol, reduces
Fine particle dosage.
Description of the drawings
Fig. 1 is a kind of structural representation of one specific embodiment of metered dose inhalation aerosol that the present invention is provided.
Reference in Fig. 1 is respectively：1st, tank is housed, 2, metering valve, 3, driver.
Specific embodiment
The invention provides a kind of medicinal aerosol formulation and metered dose inhalation aerosol, for solving：In prior art because
Ethanol is slightly soluble in for fumaric acid good fortune model sieve, after long-time is placed, diameter of aspirin particle can be assembled, and cause liquor strength uneven, from
And affect the problem of medicine delivery dose uniformity.The medicinal aerosol formulation is remained able to effectively after storage certain hour
Ensure its interior minuteness particle dosage, it is ensured that dosage delivered homogeneity.
The scheme that the present invention is provided is to be used as surfactant by adding sorbester p17 in aerosol preparations, while passing through
Restriction to sorbester p17 addition, can reach and keep that liquor strength is uniform, increase the purpose of liquid medicine stability for a long time.Tie below
The present invention is described in further detail to close embodiment, but the device of the present invention is not limited only to following examples：
Embodiment 1：
A kind of medicinal aerosol formulation, including active component and the liquefied propellant as the active component solvent, institute
Active component is stated including momestasone furoate and fumaric acid good fortune model sieve, the liquefied propellant is HFC, also including making an addition to
Ethanol and sorbester p17 in liquefied propellant, weight ratio of the sorbester p17 shared by aerosol preparations is 0.01%-
0.1%w/w.
Specifically, for the problem of above-mentioned influence of ethanol medicine delivery dose uniformity, to aerosol system in prior art
Add oleic acid in agent, but with the lengthening of aerosol preparations standing time, medicine delivery dose uniformity is gradually deteriorated.
In this programme, it is used as surfactant by adding sorbester p17 in aerosol preparations, when the sorbester p17 can be long
Between keep liquor strength uniform, so as to reach the purpose for increasing liquid medicine stability.Above to the restriction of sorbester p17 addition, it is intended to
While so that sorbester p17 plays suspending and lubrication, being unlikely to content excessively affects the generation of pharmaceutical aerosol, reduces
Fine particle dosage.
In the present embodiment, verified using comparative testing below and add sorbester p17 in aerosol preparations to liquid minuteness particle
Metering (FPD) and the impact of delivering metering homogeneity (DCU).
Comparative testing below includes five kinds of prescriptions, and the data in each prescription on the right side of each composition are the composition in aerosol system
Shared weight ratio in agent, wherein " to 100% " represent in addition to composition of other specified weights than content, aerosol preparations its
He is heptafluoro-propane by composition.
Prescription 1：
Prescription 2：
Prescription 3：
Prescription 4
Prescription 5
Above prescription is contained using PTFE (polytetrafluoroethylene (PTFE)) as the accommodating tank of coating, the aerosol system of above-mentioned formula
Agent is carried out Acceleration study June in 40 DEG C under conditions of RH=75%, and using American Pharmacopeia device dosage delivered homogeneity is determined
(DCU), minuteness particle dosage (FPD) is determined using Anderson Cascade Impactor.
As a result such as following table：
Knowable to above testing result, using sorbester p17 for 40 DEG C of the prescription of surfactant accelerate to place after June DCU and
The indexs such as FPD are superior to use the prescription of oleic acid.DCU and FPD is excellent when sorbester p17 concentration is 0.01%-0.1%w/w.
MMAD is significantly increased after i.e. prescription 1 accelerates to place, and illustrates that drug particles particle diameter increases, and causes inhalable active drug dosage
FDA is decreased obviously, and illustrates that oleic acid is acted on after placing and declines.
Meanwhile, the present embodiment also discloses a kind of medical metered dose inhalation aerosol, including medicinal aerosol formulation and is used for
Contain the pressurised metered dose inhalers of said preparation, the medicinal aerosol formulation that the preparation is provided for one scheme of any of the above.
Above aerosol has used the aerosol preparations that as above any one scheme is provided, due to the aerosol preparations
Property, so, this aerosol products can be caused for a long time to keep liquor strength uniform, keep this aerosol so as to reach
The purpose of agent properties of product stability.
Embodiment 2：
The present embodiment is further qualified on the basis of embodiment 1, used as a kind of above-described medicinal aerosol system
The further technical scheme of agent, is the gas for enabling the effective branch of the active ingredient in aerosol preparations or being deposited on human body
In pipe, bronchiole and lung, the momestasone furoate and fumaric acid good fortune model sieve are in obtaining Jing after air-flow crushing
Micro mist of the value particle diameter less than 5 microns.In this programme, due to the addition of a certain amount of sorbester p17 in aerosol preparations, although with
The active ingredient of upper median particle diameter has larger surface energy, but is still difficult to adsorb on vessel surface.
Used as a kind of liquefied propellant implementation beneficial to environmental protection, the HFC is HFA 134a, HFA 227
The mixture of any one in both or both.
Embodiment 3：
The present embodiment is further qualified on the basis of embodiment 1, used as the medical metered dose inhalation aerosol of one of the above
Further technical scheme, the pressurised metered dose inhalers include accommodating tank 1, metering valve 2 and driver 3, the accommodating tank 1
Material is magnadure, and partially or fully coating wall is lined with perfluoroparaffin high polymer inside accommodating tank 1.
Tank 1 is housed above as the storage container of aerosol preparations, due to the natural oxide film of common surface of magnesium aluminium alloy
Not only thin but also soft, low density, surface irregularity easily adsorbs the particulate in medicine, while magnesium, the aluminium of the accommodating superficial layer of tank 1
Element etc. can ooze into the liquid.In this programme, by the accommodating inwall of tank 1 partially or fully coated lining perfluoroparaffin high polymer, so,
Coated lining position can form the coating of one layer of densification, while the coating surface densification is smooth, be difficult to adsorb drug particles, it is to avoid
Aerosol preparations and the body contacts of accommodating tank 1, so, in storing process, drug particles therein are not only not for aerosol preparations
It is easily adsorbed, while aerosol preparations will not also be subject to polluting for the metal ion for discharging, so, can effectively ensure that aerosol system
The stability of agent performance.
In the present embodiment, using comparative testing below checking in the inner surface coated lining perfluoroparaffin high polymer of accommodating tank 1 in it
The impact of aerosol preparations composition, the data in following prescription on the right side of each composition are the shared weight in aerosol preparations of the composition
Amount ratio, wherein " to 100% " represents that the other compositions of aerosol preparations are seven in addition to composition of other specified weights than content
Fluoro-propane.Wherein, the material of accommodating tank 1 for being used to contain aerosol preparations in the aerosol is magnadure.
Containing momestasone furoate and formoterol fumarate micro mist and propellant HFA227e (HFC) aerosol, prescription is such as
Under：
The aerosol of above-mentioned formula is carried out Acceleration study June in 40 DEG C under conditions of RH=75%, is determined in accommodating tank 1
Surface drug residual quantity, assay method is continuously to spray aerosol up to spraying without liquid, by accommodating tank 1 in the dry ice bath
Freezing, then accommodating tank is cut, to remove metering valve 2 and take apart, the cleaning accommodating inner surface of tank 1 determines furancarboxylic acid not after constant volume with HPLC
The residual quantity of meter Song and formoterol fumarate obtains following data：
| Container tank | PTFE | Not coating |
| Momestasone furoate (mg/ bottles) | 0.07 | 1.86 |
| Formoterol fumarate (mg/ bottles) | 0.10 | 0.52 |
Wherein, the PTFE shown in above table represents that whole inner surfaces of accommodating tank 1 are applied and is lined with polytetrafluorethylecoatings coatings；
Shown not coating represents the inner surface directly contact of aerosol preparations and accommodating tank 1, i.e., not in the painting of the accommodating inner surface setting of tank 1
Layer.
The aerosol of above-mentioned formula, in 40 DEG C, is carried out Acceleration study June under conditions of RH=75%, determines magnesium in liquid
The content of ion, aluminium ion and Formoterol hydrolysate obtains following data：
Wherein, the PTFE shown in above table represents that whole inner surfaces of accommodating tank 1 are applied and is lined with polytetrafluorethylecoatings coatings；
Shown not coating represents the inner surface directly contact of aerosol preparations and accommodating tank 1, i.e., not in the painting of the accommodating inner surface setting of tank 1
Layer.
Embodiment 4：
The present embodiment is further qualified on the basis of embodiment 1, it is preferred that to reduce magnadure as far as possible to gas
The impact of sol preparation composition, the whole walls in the inside of the accommodating tank 1 are applied and are lined with perfluoroparaffin high polymer.
Preferably, as the specific implementation of the perfluoroparaffin high polymer, the perfluoroparaffin high polymer is following material
In one kind：PTFE, PEP, PFA, by PTFE, PEP, PFA three in the copolymer that arbitrarily both or three are formed.
Above content is to combine the further description that specific preferred embodiment is made to the present invention, it is impossible to assert this
The specific embodiment of invention is confined to these explanations.For general technical staff of the technical field of the invention,
The other embodiment drawn under without departing from technical scheme, should be included in protection scope of the present invention.
Claims (7)
1. a kind of medicinal aerosol formulation, including active component and the liquefied propellant as the active component solvent, it is described
Active component includes momestasone furoate and fumaric acid good fortune model sieve, it is characterised in that the liquefied propellant is HFC, is also wrapped
The ethanol and sorbester p17 made an addition in liquefied propellant is included, weight ratio of the sorbester p17 shared by aerosol preparations is
0.01%-0.1%w/w.
2. a kind of medicinal aerosol formulation according to claim 1, it is characterised in that the momestasone furoate and fumaric acid
Good fortune model sieve is micro mist of the median particle diameter obtained Jing after air-flow crushing less than 5 microns.
3. a kind of medicinal aerosol formulation according to claim 1, it is characterised in that the HFC be HFA 134a,
The mixture of any one in both HFA 227 or both.
4. a kind of medical metered dose inhalation aerosol, including medicinal aerosol formulation and the pressurised metered suction for containing said preparation
Device, it is characterised in that the medicinal aerosol formulation that the preparation is provided for any one in claims 1 to 3.
5. a kind of medical metered dose inhalation aerosol according to claim 4, it is characterised in that the pressurised metered dose inhalers
Including accommodating tank (1), metering valve (2) and driver (3), the material of the accommodating tank (1) is magnadure, is housed in tank (1)
Partially or fully coating wall is lined with perfluoroparaffin high polymer in portion.
6. a kind of medical metered dose inhalation aerosol according to claim 4, it is characterised in that the accommodating tank (1) is internal
Whole walls are applied and are lined with perfluoroparaffin high polymer.
7. a kind of medical metered dose inhalation aerosol according to claim 4, it is characterised in that the perfluoroparaffin high polymer is
One kind in following material：PTFE, PEP, PFA, by PTFE, PEP, PFA three in the copolymerization that arbitrarily both or three are formed
Thing.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1186447A (en) * | 1995-04-14 | 1998-07-01 | 葛兰素惠尔康公司 | Metered dose inhaler for slameterol |
| WO2008102128A2 (en) * | 2007-02-19 | 2008-08-28 | Cipla Limited | Pharmaceutical combinations of at least two bronchodilators or of a bronchodilator with a corticosteroid |
| CN101856362A (en) * | 2001-08-28 | 2010-10-13 | 先灵公司 | Pharmaceutical compositions for the treatment of asthma |
| 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 |
-
2016
- 2016-12-28 CN CN201611236776.9A patent/CN106619658B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1186447A (en) * | 1995-04-14 | 1998-07-01 | 葛兰素惠尔康公司 | Metered dose inhaler for slameterol |
| CN101856362A (en) * | 2001-08-28 | 2010-10-13 | 先灵公司 | Pharmaceutical compositions for the treatment of asthma |
| WO2008102128A2 (en) * | 2007-02-19 | 2008-08-28 | Cipla Limited | Pharmaceutical combinations of at least two bronchodilators or of a bronchodilator with a corticosteroid |
| 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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