CN114796166A - Aerosol containing terpene volatile oil and preparation method thereof - Google Patents
Aerosol containing terpene volatile oil and preparation method thereof Download PDFInfo
- Publication number
- CN114796166A CN114796166A CN202111098769.8A CN202111098769A CN114796166A CN 114796166 A CN114796166 A CN 114796166A CN 202111098769 A CN202111098769 A CN 202111098769A CN 114796166 A CN114796166 A CN 114796166A
- Authority
- CN
- China
- Prior art keywords
- volatile oil
- aerosol
- propellant
- pinene
- limonene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000341 volatile oil Substances 0.000 title claims abstract description 68
- 239000000443 aerosol Substances 0.000 title claims abstract description 63
- 235000007586 terpenes Nutrition 0.000 title abstract description 20
- 238000002360 preparation method Methods 0.000 title abstract description 18
- 150000003505 terpenes Chemical class 0.000 title abstract description 11
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims abstract description 64
- GRWFGVWFFZKLTI-UHFFFAOYSA-N α-pinene Chemical compound CC1=CCC2C(C)(C)C1C2 GRWFGVWFFZKLTI-UHFFFAOYSA-N 0.000 claims abstract description 63
- 239000003380 propellant Substances 0.000 claims abstract description 49
- GRWFGVWFFZKLTI-IUCAKERBSA-N 1S,5S-(-)-alpha-Pinene Natural products CC1=CC[C@@H]2C(C)(C)[C@H]1C2 GRWFGVWFFZKLTI-IUCAKERBSA-N 0.000 claims abstract description 32
- MVNCAPSFBDBCGF-UHFFFAOYSA-N alpha-pinene Natural products CC1=CCC23C1CC2C3(C)C MVNCAPSFBDBCGF-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229960005233 cineole Drugs 0.000 claims abstract description 32
- 235000001510 limonene Nutrition 0.000 claims abstract description 32
- 229940087305 limonene Drugs 0.000 claims abstract description 32
- 239000006184 cosolvent Substances 0.000 claims abstract description 22
- 239000004094 surface-active agent Substances 0.000 claims abstract description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- -1 sorbitan fatty acid ester Chemical class 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 13
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 238000009472 formulation Methods 0.000 claims description 10
- 238000007789 sealing Methods 0.000 claims description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- 229920000136 polysorbate Polymers 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 229950008882 polysorbate Drugs 0.000 claims description 5
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 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
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 239000004359 castor oil Substances 0.000 claims description 3
- 235000019438 castor oil Nutrition 0.000 claims description 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 3
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 3
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 3
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 2
- 150000005828 hydrofluoroalkanes Chemical class 0.000 claims description 2
- 239000001282 iso-butane Substances 0.000 claims description 2
- 239000001294 propane Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 34
- 230000000694 effects Effects 0.000 abstract description 12
- 210000003437 trachea Anatomy 0.000 abstract description 6
- 230000001737 promoting effect Effects 0.000 abstract description 5
- 210000003097 mucus Anatomy 0.000 abstract description 4
- 239000006186 oral dosage form Substances 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 description 33
- 238000011049 filling Methods 0.000 description 10
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000000227 grinding Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 5
- 206010006451 bronchitis Diseases 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007901 soft capsule Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000005507 spraying Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 206010062717 Increased upper airway secretion Diseases 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 208000026435 phlegm Diseases 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 238000004088 simulation Methods 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 230000000857 drug effect Effects 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 239000010419 fine particle Substances 0.000 description 3
- 238000010579 first pass effect Methods 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 229940041682 inhalant solution Drugs 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 208000023504 respiratory system disease Diseases 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 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 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010006458 Bronchitis chronic Diseases 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 208000007451 chronic bronchitis Diseases 0.000 description 2
- 230000032798 delamination Effects 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 206010039083 rhinitis Diseases 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 201000009151 chronic rhinitis Diseases 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- RFFOTVCVTJUTAD-UHFFFAOYSA-N cineole Natural products C1CC2(C)CCC1(C(C)C)O2 RFFOTVCVTJUTAD-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- UKACHOXRXFQJFN-UHFFFAOYSA-N heptafluoropropane Chemical compound FC(F)C(F)(F)C(F)(F)F UKACHOXRXFQJFN-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000510 mucolytic effect Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000013588 oral product Substances 0.000 description 1
- 229940023486 oral product Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Images
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- 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
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to the technical field of pharmaceutical preparations, in particular to an aerosol containing terpene volatile oil and a preparation method thereof. The aerosol containing terpene volatile oil provided by the invention comprises: volatile oil containing (1,8) -cineole, limonene and alpha-pinene; a propellant; a cosolvent; a surfactant. The aerosol can directly deliver the medicine to the effective part, and plays the role of dissolving and promoting the discharge of mucus in the trachea section, and has the advantages of convenient use, quick effect and increased medicine concentration at the target part compared with the existing oral dosage form.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to an aerosol containing terpene volatile oil and a preparation method thereof.
Background
The combination of natural terpene volatile oil (1,8) -cineole, limonene and alpha-pinene can improve the movement of tracheal mucosa cilium, promote the secretion of respiratory tract gland, increase the movement speed of mucus, and facilitate the discharge of sputum. The preparation on the market at present has an enteric soft capsule dosage form, and is clinically used for treating acute and chronic nasosinusitis and acute and chronic bronchitis. Because patients suffering from bronchitis, asthma and other diseases often suffer from dyspnea, most of the common clinical dosage forms are inhalation preparations, and the use compliance of the common clinical dosage forms to solid oral preparations such as soft capsules is low. In addition, the existing preparation needs to be absorbed through gastrointestinal tract after being taken orally, has a first-pass effect on liver, is delivered to a target site through systemic circulation after being taken into blood, is difficult to rapidly relieve the symptoms of excessive phlegm, and has slow effect and low bioavailability.
The aerosol is prepared by packaging the medicated solution or suspension and proper propellant in a pressure-resistant container with a special valve system, spraying the content into mist under the pressure of the propellant, and inhaling by the patient to exert local or systemic therapeutic effect. The quantitative inhalation aerosol is a common preparation for treating respiratory system diseases, has the characteristics of accurate dosage, positioning action, quick response and good stability, can avoid the first pass effect of the liver and the damage of gastrointestinal tracts, and improves the compliance and the bioavailability of patients.
CN103893165B aerosol inhalant for treating respiratory system diseases is prepared by making terpene compounds, nonionic surfactant and osmotic pressure regulator into inhalation solution for atomization, and using atomizer or nebulizer to form medicinal vapor for treating respiratory system diseases. As the terpene compounds are volatile oil substances, more surfactants are required to be added in the prepared inhalation solution, and potential adverse reaction risks are caused. In addition, the inhalation solution needs to be added into an atomizer when in use, and is inconvenient for patients to carry and use daily.
Therefore, there is a need to develop a drug containing terpene-based volatile oil which has improved bioavailability and can rapidly take effect.
Disclosure of Invention
The present invention is directed to solving, at least to some extent, one of the technical problems in the related art. Accordingly, it is an object of the present invention to provide an aerosol containing a volatile terpene oil. The aerosol can directly deliver the medicine to the trachea at the target position, is convenient for quick effect and improves the bioavailability. And the aerosol is convenient for the patient to carry and use in daily life, and improves the patient compliance.
To this end, in one aspect, the present invention provides an aerosol formulation. According to an embodiment of the invention, the aerosol comprises:
1) volatile oil containing (1,8) -cineole, limonene and alpha-pinene;
2) a propellant.
No related report that (1,8) -cineole, limonene and alpha-pinene compound terpene volatile oil is prepared into a dosage form of a quantitative inhalation aerosol is available in the existing literature. The invention prepares (1,8) -cineole, limonene and alpha-pinene into aerosol, and provides a novel inhalation phlegm-eliminating preparation which is convenient to use and takes effect quickly for patients with excessive sputum symptoms such as asthma, chronic obstructive pulmonary disease and the like. Meanwhile, the inhalation aerosol prepared by the invention does not need an atomizer, and is convenient for carrying and using by patients.
The pharmaceutical composition consisting of (1,8) -cineole, limonene and alpha-pinene has obvious mucolytic and excretion promoting effects, and is commonly used for acute and chronic rhinitis and acute and chronic bronchitis. The preparation on the market at present is an oral soft capsule, and has the problems of dysphagia and poor compliance. In addition, since the oral preparation needs to be absorbed through gastrointestinal tract, has a first-pass effect on liver, and reaches respiratory tract after entering blood to exert the drug effect, the oral soft capsule has the defect of low bioavailability and cannot directly reach a target site to exert the drug effect. The inventor finds that the aerosol containing the terpene volatile oil obtained by using the special propellant can directly deliver the medicine to an action part to play a role in dissolving and promoting the excretion of mucus in a trachea section, and has the advantages of convenient use, quick response and improvement on the concentration of the medicine at the target part compared with the oral dosage form in the market.
According to an embodiment of the invention, the aerosol comprises 1-60 parts by weight of the volatile oil;
and 20-99 parts by weight of the propellant.
According to a preferred embodiment of the invention, the aerosol comprises 3-60 parts by weight of the volatile oil;
and 45-95 parts by weight of the propellant.
In such aerosols, the propellant may be used in amounts which, if too low, result in fluctuating doses of the ejected drug. The amount of the sprayed medicine meets the requirement at the beginning, and the pressure in the tank is reduced due to insufficient propellant after the spraying agent is used, so that the amount of the sprayed medicine is reduced, and the medicine amount is not constant. And if the dosage of the propellant is too high, the corresponding drug content is low, and the drug effect is influenced.
According to the embodiment of the invention, the mass ratio of the (1,8) -cineole, the limonene and the alpha-pinene in the volatile oil is (5-70): (5-65): (5-40).
According to the embodiment of the invention, the mass ratio of the (1,8) -cineole, the limonene and the alpha-pinene in the volatile oil is (45-60): (30-43): (10-12).
According to an embodiment of the invention, the propellant is selected from one or more of hydrofluoroalkanes, dimethyl ether, saturated alkanes, compressed gas.
According to an embodiment of the invention, the saturated alkane is selected from one or more of propane, n-butane, isobutane.
By using the special propellant, the content difference of the medicine per gram is small under the initial gram and the last gram, and the medicine can be quantitatively sprayed out in the early stage and the later stage of use. And the content difference of other propellants is larger in each press of the medicament in the early stage and the later stage of the spraying, so that the effect is poorer and the requirements are not met when the propellant is applied to the aerosol of the invention.
According to an embodiment of the invention, the aerosol further comprises a surfactant and/or a co-solvent.
According to an embodiment of the invention, the surfactant is selected from one or more of polysorbate, sorbitan fatty acid ester, polyoxyethylene castor oil, oleic acid, phosphatidylcholine.
The polysorbate is Tween surfactant, and the sorbitan fatty acid ester is span surfactant.
According to an embodiment of the invention, the surfactant is polysorbate.
According to an embodiment of the present invention, the cosolvent is selected from one or more of absolute ethyl alcohol, polyethylene glycol and propylene glycol.
According to an embodiment of the invention, the co-solvent is selected from one or more of absolute ethanol and polyethylene glycol.
The absolute ethyl alcohol and the polyethylene glycol have good mutual dissolving effect with the volatile oil, and the layering phenomenon can not occur.
According to an embodiment of the present invention, the surfactant is 0 to 10 parts by weight.
According to the embodiment of the invention, the cosolvent is 5-50 parts by weight.
The invention prepares the terpene medicine composition (1,8) -cineole, limonene and alpha-pinene and proper surfactant and/or cosolvent and propellant into aerosol, and can directly deliver the medicine to the effective part to play the role of dissolving and promoting the excretion of mucus in the trachea segment. In pharmacodynamic tests of the rat phlegm-discharging promoting effect, compared with an oral preparation, the aerosol prepared by the invention can obviously increase the phlegm-discharging amount of the trachea section of the rat under a lower administration dosage, and the onset time is about 1 hour earlier than that of the oral preparation. Therefore, compared with the existing oral dosage form, the aerosol prepared by the invention has the advantages of convenient use, quick response and improvement of the concentration of the target part medicament.
In a second aspect, the present invention provides a method of producing an aerosol formulation according to the first aspect. According to an embodiment of the invention, the method comprises:
charging the raw materials into a pressure-resistant container, inserting a valve into the pressure-resistant container, sealing the valve, charging a propellant to prepare the aerosol,
wherein the raw materials comprise volatile oil containing (1,8) -cineole, limonene and alpha-pinene.
According to an embodiment of the invention, the feedstock further comprises a surfactant and/or a co-solvent.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 shows the structure of a bipolar impactor, wherein A is a nozzle adapter; a B simulation part; c, simulating a neck; d is a first-level distribution bottle; e is a connecting pipe; f is an outlet three-way pipe; g is a spray head; h is a two-stage distribution bottle, and the length of each part is represented by numbers in the figure and is in mm.
Detailed Description
According to the specific embodiment of the invention, the prescription composition of the terpene volatile oil inhalation aerosol provided by the invention comprises a medicament, a surfactant, a cosolvent and a propellant. The composition of the compound terpene volatile oil inhalation aerosol is as follows:
(1) (1,8) -cineole, limonene and alpha-pinene, wherein the component of the compound volatile oil is 3-60 parts by weight;
(2) 0-10 parts of surfactant;
(3) 5-50 parts of cosolvent;
(4) 40-95 parts of propellant;
the medicine is a mixed raw material of (1,8) -cineole, limonene and alpha-pinene, wherein the mass ratio of the (1,8) -cineole, limonene and alpha-pinene in the volatile oil is (5-70): (5-65): (5-40).
According to another embodiment of the invention, the compound terpene volatile oil inhalation aerosol provided by the invention comprises the following components:
(1) (1,8) -cineole, limonene and alpha-pinene, wherein the component of the compound volatile oil is 1-60 parts by weight;
(2) 20-99 parts of propellant;
the medicine is a mixed raw material of (1,8) -cineole, limonene and alpha-pinene, wherein the mass ratio of the (1,8) -cineole, limonene and alpha-pinene in the volatile oil is (5-70): (5-65): (5-40).
According to another embodiment of the invention, the compound terpene volatile oil inhalation aerosol provided by the invention comprises the following components:
(1) (1,8) -cineole, limonene and alpha-pinene, wherein the component of the compound volatile oil is 3-60 parts by weight;
(2) propellant HFA or dimethyl ether 40-95 weight portions;
the medicine is a mixed raw material of (1,8) -cineole, limonene and alpha-pinene, wherein the mass ratio of the (1,8) -cineole, limonene and alpha-pinene in the volatile oil is (45-60): (30-43): (10-12).
The following describes embodiments of the present invention in detail. The following examples are illustrative only and are not to be construed as limiting the invention.
The examples, where specific techniques or conditions are not indicated, are to be construed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or instruments used are conventional products which are commercially available, and are not indicated by manufacturers.
Example 1
(1) The compound volatile oil component composed of (1,8) -cineole, limonene and alpha-pinene is 7.41%;
(2) propellant HFA-134a 92.59%.
Wherein the compound volatile oil contains (1,8) -cineol 50%, limonene 35% and alpha-pinene 15%.
The preparation method comprises the following steps: filling the compound volatile oil into a pressure-resistant container, inserting a valve, sealing the valve, filling 10g of propellant HFA-134a, detecting leakage in a water bath at 50 ℃, and preparing into an inhalation aerosol.
Example 2
A compound terpene volatile oil inhalation aerosol comprises the following components in percentage by weight:
(1) (1,8) -20% of compound volatile oil consisting of cineole, limonene and alpha-pinene;
(2) surfactant span 852%;
(3) and 78% of propellant dimethyl ether.
Wherein the compound volatile oil contains (1,8) -cineol 45%, limonene 43% and alpha-pinene 12%.
The preparation method comprises the following steps: mixing the above volatile oil with span 85, packaging in pressure-resistant container, inserting valve, sealing valve, packaging propellant, and performing water bath leakage detection at 50 deg.C to obtain inhalation aerosol.
Example 3
A compound terpene volatile oil inhalation aerosol comprises the following components in percentage by weight:
(1) (1,8) -cineole, limonene and alpha-pinene to form 60% of compound volatile oil;
(2) surfactant tween 801%;
(3) cosolvent anhydrous ethanol 10%;
(4) the propellant compresses air 29%.
Wherein the compound volatile oil contains (1,8) -cineol 60%, limonene 30% and alpha-pinene 10%.
The preparation method comprises the following steps: mixing the above volatile oil with tween 80 and anhydrous ethanol, filling into a pressure-resistant container, inserting valve, sealing valve, filling propellant, and performing water bath leakage detection at 50 deg.C to obtain inhalation aerosol.
Example 4
A compound terpene volatile oil inhalation aerosol comprises the following components in percentage by weight:
(1) (1,8) -cineole, limonene and alpha-pinene, 10 percent of compound volatile oil;
(2) 50% of cosolvent absolute ethyl alcohol;
(3) propellant HFA-22740%.
Wherein the compound volatile oil contains (1,8) -cineole 50%, limonene 40% and alpha-pinene 10%.
The preparation method comprises the following steps: mixing the above compound volatile oil and anhydrous ethanol, filling into pressure-resistant container, inserting valve, sealing valve, filling propellant, and performing water bath leakage detection at 50 deg.C to obtain inhalation aerosol.
Example 5 propellant screening
2.0g of the compound volatile oil in the embodiment 1 is put into a pressure-resistant container, 10g of different types of propellants are filled in the container through inserting a valve and sealing the valve, and the inhalation aerosol is prepared by comparing the content of the medicaments with different knock times. The results of the tests are given in the following table:
TABLE 1
The test result shows that the propellant tetrafluoroethane HFA-134a, the heptafluoropropane HFA-227 and the dimethyl ether have small difference in the content of the medicine per gram under the initial gram and the last gram, and the quantitative ejection of the medicine in the early stage and the later stage of use can be ensured. The propellant compressed air, the compressed nitrogen and the n-butane have different drug contents in the early stage and the later stage of the injection, but can also be used as the propellant of the aerosol, and can meet the requirement of the field on the aerosol. Therefore, to ensure the uniformity of the formulation during use, HFA-134a, HFA227 or dimethyl ether is preferably selected as the propellant in the formulation.
Example 6 cosolvent species screening
2.0g of the compound volatile oil in the embodiment 1 is put into a pressure-resistant glass transparent container, 2.0g of different cosolvents are respectively added, 10.0g of propellant HFA134a is injected after sealing, the container is placed at 25 ℃ for 48 hours, and whether the solution is layered or not is observed. The results of the tests are given in the following table:
TABLE 2
| Numbering | Cosolvent | Phenomenon(s) |
| 1 | Is free of | Non-delamination of liquid |
| 2 | Anhydrous ethanol | Non-delamination of liquid |
| 3 | Propylene glycol | Layering |
| 4 | Polyethylene glycol 400 | Non-delamination of liquid |
| 5 | Glycerol | Layering |
Test results show that the absolute ethyl alcohol and the polyethylene glycol 400 have good mutual solubility with the compound volatile oil, and the propylene glycol and the glycerol cannot be mutually dissolved and have a layering phenomenon when being added into the compound volatile oil and the propellant. Therefore, absolute ethanol and polyethylene glycol 400 are more suitable as co-solvents in the formulation.
EXAMPLE 7 Co-solvent dosage screening
2.0g of the compound volatile oil in the embodiment 1 and absolute ethyl alcohol or polyethylene glycol 400 with different concentrations are filled into a pressure-resistant glass transparent container, the container is sealed and then injected with 134a 10g of propellant HFA134, and whether the solution is layered or not is observed. The results of the tests are given in the following table:
TABLE 3
| Numbering | Cosolvent | Amount of prescription | Phenomenon(s) |
| 1 | Is free of | 0 | Not layering |
| 2 | Anhydrous ethanol | 0.5g | Without delamination |
| 3 | Anhydrous ethanol | 1.0g | Not layering |
| 4 | Anhydrous ethanol | 2.0g | Without delamination |
| 5 | Anhydrous ethanol | 3.0g | Not layering |
| 6 | Anhydrous ethanol | 4.0g | Not layering |
| 7 | Polyethylene glycol 400 | 0.5g | Not layering |
| 8 | Polyethylene glycol 400 | 1.0g | Not layering |
| 9 | Polyethylene glycol 400 | 2.0g | Not layering |
| 10 | Polyethylene glycol 400 | 3.0g | Layering |
| 11 | Polyethylene glycol 400 | 4.0g | Layering |
When the prescription amount of the polyethylene glycol 400 is more than 3.0g, the liquid medicine has a layering phenomenon, the mutual dissolving effect of the absolute ethyl alcohol, the compound volatile oil and the propellant is good, and 0.5g-4.0g of the absolute ethyl alcohol can be selected as the cosolvent of the product.
EXAMPLE 8 selection of the type and amount of surfactant
2.0g of the compound volatile oil in the embodiment 1 and the surfactant with different concentrations are filled into a pressure-resistant glass transparent container, the container is sealed and then injected with 134a 10g of propellant HFA, and whether the solution is layered or not is observed. The results of the tests are given in the following table:
TABLE 4
According to test results, polysorbate 80 has the best mutual dissolving effect in the compound volatile oil and the propellant, and can generate a surface activity effect. Span 85 has certain surface activity, polyoxyethylene (35) castor oil, oleic acid and phosphatidylcholine can only be dissolved in a small amount in the compound volatile oil and the propellant, and the dosage needs to be controlled. Thus, polysorbate 80 is more suitable as a prescription surfactant.
EXAMPLE 9 screening of Compound volatile oil to propellant ratio
Respectively filling 0.3g, 0.5g, 0.8g and 1.0g of the compound volatile oil in the embodiment 1 into a pressure-resistant container, inserting a valve, sealing the valve and filling a propellant HFA134a 10g to prepare the compound volatile oil inhalation aerosol.
Taking 1 bottle of the test product, shaking, discarding 5 sprays, immersing an aluminum can and a driver into a beaker containing a proper amount of methanol absorption liquid, spraying for 10 times, wherein the spraying interval is 5s, slowly shaking, taking out, washing the driver with methanol, combining a washing solution and the absorption liquid, and measuring the content of each press of the three components of the compound volatile oil by adopting a gas chromatography.
The content of each drug in the aerosol with different compound volatile oil contents is as follows:
TABLE 5
| Content of compound volatile oil | Content of medicine per press |
| 0.3g | 1.70mg |
| 0.5g | 2.84mg |
| 0.8g | 4.68mg |
| 1.0g | 5.89mg |
The daily dose of the currently marketed enteric soft capsules is 900 mg/day, and the calculated amount of the medicine which can reach the bronchus is about 1%, so that the amount of the medicine in the trachea section after the medicine is taken is about 9 mg. Therefore, the aerosol with the content of 0.8-1.0 g of effective components is suitable to be used as a substitute product of an oral product through preliminary judgment, and the daily administration frequency can be adjusted according to individual conditions.
Example 10 Total knock times per bottle
Filling 0.8g of the compound volatile oil in the example 1 into a pressure-resistant container, inserting a valve, sealing the valve, filling a propellant HFA134a 10g, and performing water bath leakage detection at 50 ℃ to prepare the compound volatile oil inhalation aerosol. 5 bottles of samples were taken and the total number of strokes per bottle was determined. The test results are as follows:
TABLE 6
Since each bottle contains 0.8g of the compound volatile oil, the marked amount of the inhalation aerosol is 4.5 mg/press.
EXAMPLE 11 delivered dose uniformity of Aerosol
Taking a compound volatile oil inhalation aerosol 1 bottle, and respectively measuring the drug content of each press of 1-10 presses, 80-90 presses and 150-160 presses. The test results are as follows;
TABLE 7
| Different number of press buttons | Content of medicine per press (mg) | Percent of indicated amount (%) |
| 1-10 | 4.32 | 96.0％ |
| 80-90 | 4.57 | 101.6％ |
| 150-160 | 5.02 | 111.6％ |
The results show that there is an increasing trend in the last strokes of the aerosol, but the limit requirement of 80% -120% is met.
EXAMPLE 12 Aerosol Fine ion aerodynamic Properties determination
15g of the sample prepared according to the ratio of the number 3 in the example 7 is put into a pressure-resistant container, a valve is inserted and sealed, and the propellant HFA134a 10g is filled to prepare the compound volatile oil inhalation aerosol which is used by a double-stage impactor (glass instrument manufacturing factory in the great wall of the Tian Chang).
The structure of the two-stage impactor is shown in fig. 1, wherein A is a suction nozzle adapter used for connecting a suction device; the simulation part B is made of a modified 50ml round-bottom flask, the inlet of the simulation part is an 29/32 ground pipe, and the outlet of the simulation part is a 24/29 ground pipe; c, simulating a neck; d is a first-level distribution bottle made of 24/29 ground 100ml round bottom flask, and the outlet is 14/23 ground pipe; e is a connecting pipe which is connected with D by a 14-port grinding plug; f is an outlet three-way pipe, the outlet on the side surface is a grinding plug with 14 ports, the upper end of the grinding plug is connected with a plastic screw cap to seal the grinding plug with E and F, and the outlet on the lower end of the grinding plug is a grinding plug with 24/29 ports; g is a nozzle made of a polypropylene material, the bottom of the nozzle is provided with 4 spray holes with the diameter of 185mm +/-0.123 mm, and the center of each spray hole is provided with a projection with the diameter of 2mm and the height of 2 mm; h is a two-stage distribution bottle, 24/29 ground 250mL Erlenmeyer flask. The structures of the parts A-G are connected in sequence in the figure.
The amount of fine particles in the aerosol was measured by the above two-stage impactor, and the results are shown in Table 8 below.
TABLE 8
| Active ingredient | First-level distribution bottle receiving ratio | Two-stage distribution bottle acceptance ratio | Amount of fine particles |
| (1,8) -cineole | 13.2％ | 86.8％ | 86.8％ |
| Limonene | 15.0％ | 85.0％ | 85.0％ |
| Alpha-pinene | 14.7％ | 85.3％ | 85.3％ |
The three effective components in the fine particles can reach more than 85%, and the fine ions have a large proportion, so that the medicine can be effectively distributed to the lung.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.
Claims (10)
1. An aerosol formulation, comprising:
1) volatile oil containing (1,8) -cineole, limonene and alpha-pinene;
2) a propellant.
2. Aerosol formulation according to claim 1, comprising 1 to 60 parts by weight of the volatile oil;
and 20-99 parts by weight of the propellant.
3. Aerosol according to claim 2, characterized in that the mass ratio of the (1,8) -cineol, limonene to alpha-pinene in the volatile oil is (5-70): (5-65): (5-40);
optionally, the mass ratio of the (1,8) -cineole, limonene and alpha-pinene in the volatile oil is (45-60): (30-43): (10-12).
4. Aerosol according to claim 1, wherein the propellant is selected from one or more of hydrofluoroalkanes, dimethyl ether, saturated alkanes, compressed gases;
optionally, the saturated alkane is selected from one or more of propane, n-butane, isobutane.
5. The aerosol formulation of claim 2, further comprising a surfactant and/or a co-solvent.
6. The aerosol formulation of claim 5, wherein the surfactant is selected from one or more of polysorbate, sorbitan fatty acid ester, polyoxyethylene castor oil, oleic acid, phosphatidyl choline;
optionally, the surfactant is a polysorbate.
7. Aerosol according to claim 5, wherein the co-solvent is selected from one or more of absolute ethanol, polyethylene glycol, propylene glycol, glycerol;
optionally, the co-solvent is selected from one or more of absolute ethanol and polyethylene glycol.
8. Aerosol according to claim 6 or 7, characterized in that the surfactant is present in an amount of 0 to 10 parts by weight;
optionally, the cosolvent is 5-50 parts by weight.
9. A method of producing an aerosol formulation as claimed in any one of claims 1 to 8, comprising:
charging the raw materials into a pressure-resistant container, inserting a valve into the pressure-resistant container, sealing the valve, charging a propellant to prepare the aerosol,
wherein the raw materials comprise volatile oil containing (1,8) -cineole, limonene and alpha-pinene.
10. The method of claim 9, wherein the feedstock further comprises a surfactant and/or a co-solvent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2021101351518 | 2021-01-29 | ||
| CN202110135151 | 2021-01-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114796166A true CN114796166A (en) | 2022-07-29 |
Family
ID=82525453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111098769.8A Pending CN114796166A (en) | 2021-01-29 | 2021-09-18 | Aerosol containing terpene volatile oil and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114796166A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1331581A (en) * | 1998-11-25 | 2002-01-16 | 奇斯药制品公司 | Pharmaceutical aerosol compsn. contg. HFA227 and HFA 137 |
| CN101569684A (en) * | 2008-05-04 | 2009-11-04 | 浙江省中药研究所有限公司 | Inhalation aerosol of plant extract for treating asthma and preparation method |
| WO2010052466A2 (en) * | 2008-11-04 | 2010-05-14 | Cipla Limited | Pharmaceutical aerosol composition |
| CN103893165A (en) * | 2014-03-27 | 2014-07-02 | 北京九和药业有限公司 | Nebulizer for treating respiratory system diseases |
| CN105456234A (en) * | 2014-09-12 | 2016-04-06 | 天津新济复兴药业科技有限公司 | Novel propellant asarone inhalation aerosol and preparation method thereof |
| CN108815234A (en) * | 2018-08-23 | 2018-11-16 | 北京九和药业有限公司 | A kind of application of pharmaceutical composition in the drug of preparation treatment pulmonary disease |
-
2021
- 2021-09-18 CN CN202111098769.8A patent/CN114796166A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1331581A (en) * | 1998-11-25 | 2002-01-16 | 奇斯药制品公司 | Pharmaceutical aerosol compsn. contg. HFA227 and HFA 137 |
| CN101569684A (en) * | 2008-05-04 | 2009-11-04 | 浙江省中药研究所有限公司 | Inhalation aerosol of plant extract for treating asthma and preparation method |
| WO2010052466A2 (en) * | 2008-11-04 | 2010-05-14 | Cipla Limited | Pharmaceutical aerosol composition |
| CN103893165A (en) * | 2014-03-27 | 2014-07-02 | 北京九和药业有限公司 | Nebulizer for treating respiratory system diseases |
| CN105456234A (en) * | 2014-09-12 | 2016-04-06 | 天津新济复兴药业科技有限公司 | Novel propellant asarone inhalation aerosol and preparation method thereof |
| CN108815234A (en) * | 2018-08-23 | 2018-11-16 | 北京九和药业有限公司 | A kind of application of pharmaceutical composition in the drug of preparation treatment pulmonary disease |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2129424C1 (en) | Aerosol pharmaceutical composition, a method of treatment of patients with respiratory diseases | |
| CA2115065C (en) | Ultrafine particle powder for inhalation and method for production thereof | |
| CN104055765B (en) | Therapeutic alliance for COPD | |
| McDonald et al. | Transition to CFC-free metered dose inhalers—into the new millennium | |
| EP1073429B1 (en) | Aerosol formulations of salmeterol xinafoate | |
| AU2011316124B2 (en) | Nasal spray device | |
| WO1995017195A1 (en) | Flunisolide aerosol formulations | |
| BG98897A (en) | Medicaments | |
| BG65883B1 (en) | Stable pharmaceutical solution formulations for pressurised metered dose inhalers | |
| EA018547B1 (en) | Metered dose inhaler actuator | |
| CN105101955A (en) | Composition comprising at least two dry powders obtained by spray drying to increase the stability of the formulation | |
| Deb et al. | Aerosols in pharmaceutical product development | |
| RU2567040C2 (en) | Aerosol formulation for treating chronic obstructive pulmonary disease | |
| TWI449523B (en) | Pharmaceutical aerosol formulations of formoterol and beclometasone dipropionate | |
| CA2909124C (en) | A pharmaceutical composition containing budesonide and formoterol | |
| CN114796166A (en) | Aerosol containing terpene volatile oil and preparation method thereof | |
| CN104208701A (en) | Compound inhalation preparation containing antifungal drug | |
| US20230057979A1 (en) | Medicinal compositions for carbon dioxide based metered dose inhalers | |
| EP2167042B1 (en) | Pharmaceutical aerosol compositions comprising fluticasone | |
| AU2021200396B2 (en) | Pharmaceutical composition containing budesonide and formoterol | |
| KR20220108047A (en) | Stainless steel cans for pressurized metered dose inhalers | |
| Mao et al. | Pharmaceutical aerosols | |
| Pritchard | Recent advances in drug delivery via pressured metered-dose inhalers | |
| KR20040086370A (en) | Carboxylic acid compounds for use as surfactants | |
| AU2015201102A1 (en) | Nasal spray device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |