US2868691A - Self-propelling compositions for inhalation therapy containing a salt of isoproterenol or epinephrine - Google Patents

Self-propelling compositions for inhalation therapy containing a salt of isoproterenol or epinephrine Download PDF

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US2868691A
US2868691A US572788A US57278856A US2868691A US 2868691 A US2868691 A US 2868691A US 572788 A US572788 A US 572788A US 57278856 A US57278856 A US 57278856A US 2868691 A US2868691 A US 2868691A
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medicament
composition
freon
self
isoproterenol
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US572788A
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Porush Irving
George L Maison
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Riker Laboratories Inc
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Riker Laboratories Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/007Pulmonary tract; Aromatherapy
    • A61K9/0073Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/008Sprays 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]
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • a number of previous eflorts have been directed to the preparation of medicament-containing, pharmaceutical preparations for use in inhalation therapy.
  • Thes'e preparations suffer from one or more shortcomings. In many cases they require cumbersome mechanical devices to dispense the medicament. Some of these devices employ a rubber airbulb to aspirate the medicament. This often requires substantial physical effort on the "part of the user. In other cases the vehicle for the medicament may possess irritating properties which mitigate against the use of the compositions for inhalation therapy where delicate mucous membranes may be aflected. In some cases Where a fixed dosage is required these'compositions are not conveniently dispensed in measured, constant amounts. For these reasons, as well as others, the benefits of inhalation therapy have not'been fully realized and progress in this mode of medication has lagged.
  • compositions invide a self-propelling therapeutic composition for inhalation therapy which maybe packaged with safety in suitable low pressure containers,;such as frangible containers, or in containers having a dispensing valve construction which will permit dispensing jmeasui'ed, constant doses of "the medicament.
  • Still another object of the present invention is to provide a stable therapeutic composition containing a liquified non-toxic propellent material which is not subject to erratic pressure variations and which imparts easily controlled pressures at room or ambient temperatures to the container in which the composition is stored and dispensed from.
  • compositions of the present invention comprise a medicament dissolved in a non-toxic
  • liquid propellant in thenature of a fluorinated or fluorochlorinated lower aliphatic hydrocarbon, preferably with the aid of a co-solvent for both the medicament and the a medicament in aerosol form for inhalation therapy.
  • the non-toxic, liquid propellant shall be a fluorinated or a fluorochlorinated lower saturated aliphatic hydrocarbon, and preferably a halogenated alkane containing not more than 2 carbon atoms and at least 1 fluorine atom, or mixtures thereof.
  • the propellants shall possess a boiling point of less than F. at 760 mm. pressure.
  • propellants examples include dichlorodifiuoromethane (Freon 12), dichlorotetrafluoroethane (Freon 114) CCIF CClF trichloromonofluoromethane (Freon 11), dichloromonofiuoromethane (Freon 21), and Propellants with improved vapor pressure characteristics may be obtained by using certain mixtures of these compounds, e.
  • Freon 11 and Freon 12, or Freon 12 and Freon 114 For example, dichlorodifluoromethane, which has a vapor pressure of about 70 pounds per square inch .gauge and 1,2-dichloro-1,1,2,2-tetrafluoroethane (Freon 114), with a vapor pressure of about -13 pounds per square inch. gauge at 70 F., may be mixed in various proportions to form a propellant having an intermediate vapor pressure which is well suited for use in relatively low pressure containers.
  • the vapor pressure of the propellant employed shall itself be between about 25 and 65 pounds per square inch gauge at 70 F., and preferably between about 30 and 40 pounds per square inch gauge at that temperature.
  • a one-component propellant defined'for use in thecomposition was found to give a'composition with gaugepressures in the rangeof 55to 65 pounds per square inch at 70 F., which are usable safely with metal containers.
  • the two-component propellants such as equalweight mixtures of Freon 12 and "Freon 11, were found to give gauge pressures in the range of 2 0 to 40 pounds per square inch at 70 F., which are usable safely with specially reinforced glass containers.
  • the medicament employed in a composition according to this invention can be one which is therapeutically ef fective when administered'by inhalation and which may be brought into stable solution in any of the above defined liquified propellants, if necessary, with the aid of a cosolvent and/ or stabilizing substance.
  • One type of medicament which can be employed satisfactorily is the vasoconstrictive amines and their acid-addition salts.
  • other types of medicaments such :as hormones, enzymes, alkaloids, steroids, analgesics, broncho-dilators,. antihistamines, 'antitussives, anginal preparations, antibiotics and sulfonamides and synergistic combinations of these,v
  • Examples of the medicaments which may be employed in producing the compositions of this invention are: isoproterenol hydrochloride [u-(isopropylaminomethyl) protocatechuyl alcohol], phenylephrine, epinephrine, ephedrine, narcotine, codeine, atropine, ergotamine, scopolamine, colchicine, cortisone and alkyl nitrites, such'as amyl nitrite or octyl nitrite.
  • the co-solvent maybe any liquid substance which assists in. dissolving the medicament in the liquified propellant and which is chemically inert to the medicament in the sense that it does not promote the decomposition of this substance.
  • Suitable co-solvents are intermediate in polarity between the propellant and the medicament.
  • the co-solvents have the property of being a solvent for the medicament and soluble in the propellants prescribed for use in this invention.
  • the co-solvent beside being chemically inert toward the medicament, should benontoxic andwithout undesirable effects on inhalation in the amount present in the aersol produced.
  • the co-solvent shall have as low a boiling point as possible and prefer-. ably not higher than 212 F. at atmospheric pressure. Examples of satisfactory co-solvents include non-toxic loweralcohols and eth ers, e. g., ethanol, diethyl ether, chloroform, mixtures of ethanol and wate r, and mixtures of chloroform and ethanol.
  • the stabilizers or anti-oxidants which .may be employed are stronger reducing agents than the medicament and which are non-toxic, such as the alkali-metal bisu'lfites (sodium bisulfite), alkali-metal ascorbates (sodium ascorbate), ascorbic acid, nordihydroguaiaretic acid, 2- tertiarybutyl-4-hyd'roxy anisole, 3-tertiarybutyl-4-hydroxy anisole, butylated hydroxytoluene' (sold under the trademark Tenox BHT), ethylhydro-caffeate, etc. It is normallynot necessary to employ -a stabilizer in an amount in excess'of 0.25% by-weight ofthe composition.
  • Spray pattern involves the delivery rate, the particle size distribution and the spray angle.
  • the spray pattern is affected by mechanical factors, e. g., valve construction and orifice size and shape, and by the characteristics of the composition, e. g., viscosity, vapor pressure, type and percentage of propellant.
  • thecomposition lack-suificient propellent force and consequently the'inadequate aerosolization of the medicament results in a particle size distribution which is not efiiciently absorbed in-the' bronchioles and alveoli.
  • the composition may become unstable during storage and-the medicament may precipitate from the composition.
  • thecompositions may develop undesirably high pressures.
  • the open container and its contents are then cooled, preferably to a temperature below the boiling point of the propellant to be employed. A temperature of 25 F. is usually satisfactory.
  • a measured quantity of the liquified propellant which also has been cooled below its boiling point is then introduced into the container and mixed with the solution already present. The quantities of the components introduced into the container are calculated to provide the desired concentration of each in the final composition.
  • the container is sealed with a closure equipped with asuitable dispensing valve arrangement. Upon warming to room temperature the Q mnts of the container are mixed by agitation of the containerto insure complete solution of the medicament.
  • the liquid propellant constitute at least about 50% by weight of the total composition upward to about 90%. It is preferred that the propellant constitute between about 55% or 60% and 80% by weight of the total composition.
  • the amount and constitution of the co-solvent is largely dependent upon the solubility characteristics of the medicament employed. In most cases it has been found that satisfactory results are obtained where the co-solvent constitutes between about 5% or 10% and 40%, and preferably between abont 20% and 40%'-- v we hto the t a .cQmP s t Qn- .lf to!
  • the amout of medicament shall generally constitute from about 0.1% to 20%, and preferably from about 0.1% to 2% by weight of the'composition.
  • the propellant makes-upthe difference 'betwen the proportions of medicamennco-solvent, stabilizer and 100%.
  • novel compositions of the-invention maybe-prepared and containers filled with them by-means of-the following process:
  • Asuitable measured quantity-of the medicament- is mixed with, and dissolved in, a measured amountof the co-solvent. .A stabilizer, if desired,- is added.
  • A- measured quantity-zof the resultingsolution isythea ntra used percentages bysweight of the total composition.
  • Example 3 I Percent Isoproterenol l ICl ate Ethan We Trichloromonotiuoromethane (Freon 1-1)
  • Example 6 g 1 V H Percent Narcotine v 1 Water 0.65 Ethanol (absolute) a 12.35 Chloroform 20.6
  • Dichlorodifiuorornethane (Freon 12) i f-'3 4.8
  • Example 10 I I I P ercent Atropine 0.1 Ethanol 95% a 9.9 Dichlorodifluoromethane (Freon 12) 45 Dichlorotetrafluoroethane (Freon 114) 45 1 100
  • Example 11 i t Percent Octyl nitrite 0.1 Ethanol 95 9.9 Dichlorotetrafiuoroethane .(Freon 114) 55.4 Dichlorodifiuoromethane (Freon 12) 34.6
  • colchicine cortisone, amyl nitrite, etc.
  • compositions in accordance with this invention are characterized by a clear, sparkling appearancewith the advantage that it is easy to observe when the'container is nearly empty. It is recommended for added safety that the glass bottles be coated with a plastic film, preferably clear.
  • 'Aldip-tube of suitable material may be connected with the opening containing the valve arrangement and extendingfto the bottom of the container or an inverted system without a dip-tube may be'-used.
  • the composition is expelled through the opening in the form of a fine stream to form an aerosol of the medicament.
  • the opening is desirably constructed to provide a small orifice so as to expel a fine spray of the composition.
  • a self-propelling pharmaceutical composition capable of providing a medicament in aerosol formsuitable for inhalation therapy, comprising as the medicament a water-soluble acid-addition salt of a bronchodi lator amine selected from the class consisting of isoproterenol and epinephrine, said medicament comprising between about 0.1% and 2% of the composition, as a co solvent for said medicament, an aqueous ethanol mixture in an amount comprising between about 20% to 40% of the composition, the water in said cosolvent comprising between about 1.5% and 2% 'of the total com'-' position, and as a liquefied non-toxic propellant componut 21 halogenated lower alkane containing at least 1 fluorine atom and not more than 2 carbon atoms and having a vapor pressure of between about 20 and 65 pounds per square inch gauge at F., said liquefied propellantfcomponent comprising substantially the re mainder of the composition.
  • a self-propelling pharmaceutical composition as defined by claim .1 containing about 0.25% ,isoprotera enol hydrochloride, about-1.5% water, about 33.25%- ethanol, and the remainder being a liquefied'non-toxie propellant as ,defi ne d by claim 1.
  • a package comprising a pressure-tight container having a valve-controlled opening and containing a selfpropelling pharmaceutical composition capable of providing a medicament in aerosol form suitable forinhal-ation therapy, comprising as a medicament a water-soluble acid-addition salt ofa bronchodilator' amine selected from the. class consisting of. isoproterenol and epinephrine,- said medicament comprising between about 0.1% and 2% of the composition, as. a .cosolvent-for said medicament an aqueous ethanol mixture. in an. amount comprising- -betwee about 20%. and 40% of the composition, the waterin said cosolvent comprising between about 1.5% and 2% of the total.
  • a selfpropelling pharmaceutical composition capable of providing a medicament in aerosol form suitable forinhal-ation therapy, comprising as a medicament a water-soluble acid-addition salt ofa bronchodilator' amine selected from the. class consisting of. isoproterenol and
  • said liquefied propellant component comprising substantia l lythe remainder of the composition.
  • a method oi producing a measured dose ofimedicament in aerosol form suitable for inhalation therapy whi omprise f rm n a q d mposition oira' msdis mentqnthetorm o a atqrs luhleaci d ition altof abronchodilatoramine selected from the class consisting otisoproterenol and epinephrine, said medicamom.
  • composition comprising between about 0.1% and 2% of the composition, said medicament being dissolved ina mixture of a co-solvent and a liquefied non-toxic propellant component, said co-solvent comprising an aqueous ethanol gniggtpre i n an amount comprising between about 2 1 and 49% oi the total.
  • nqns9lve n t comprising between about l.5'%.wand'2%' or the total composition, said liquefied non-toxic; propellant component comprising a halogenated lower alkane containing at least 1 fluorine atom and not more than 2 carbon atoms and having a--.v-ap,or pressure of between ab9u-t'20 and pounds per square inch gauge at F., said liquefied propellant component comprising substan-v a ly e .remainder ofthe. composition,v .and dispensing he. l iq isl .qq l position. from. a. pressure-tight. container through a control valve for-self-propelled delivery in the f rm of an. a lQS01' l'QSU1l1l1g from the rapidvaporization of...the propellant.
  • propellant component comprising a halogenated lower alkane containing at least 1 fluorine atom

Description

United States Patent SELF-PROPELLING COMPOSITIONS FOR INHALA-I TION THERAPY CONTAINING A SALT OF ISO- PROIERENOL R EPINEPHRIYE Claims. (Cl. 167-54) This invention relates to novel medicament-containing,
self-propelling compositions for inhalation'therapy.'-
A number of previous eflorts have been directed to the preparation of medicament-containing, pharmaceutical preparations for use in inhalation therapy. Thes'e preparations suffer from one or more shortcomings. In many cases they require cumbersome mechanical devices to dispense the medicament. Some of these devices employ a rubber airbulb to aspirate the medicament. This often requires substantial physical effort on the "part of the user. In other cases the vehicle for the medicament may possess irritating properties which mitigate against the use of the compositions for inhalation therapy where delicate mucous membranes may be aflected. In some cases Where a fixed dosage is required these'compositions are not conveniently dispensed in measured, constant amounts. For these reasons, as well as others, the benefits of inhalation therapy have not'been fully realized and progress in this mode of medication has lagged.
It is, therefore, one object of this invention to overcome the disadvantages of the prior art compositions invide a self-propelling therapeutic composition for inhalation therapy which maybe packaged with safety in suitable low pressure containers,;such as frangible containers, or in containers having a dispensing valve construction which will permit dispensing jmeasui'ed, constant doses of "the medicament.
Still another object of the present invention is to provide a stable therapeutic composition containing a liquified non-toxic propellent material which is not subject to erratic pressure variations and which imparts easily controlled pressures at room or ambient temperatures to the container in which the composition is stored and dispensed from.
Other objects will be apparent to those skilled in the .art from reading the description which follows.'
The self-propelling compositions of the present invention comprise a medicament dissolved in a non-toxic,
liquid propellant in thenature of a fluorinated or fluorochlorinated lower aliphatic hydrocarbon, preferably with the aid of a co-solvent for both the medicament and the a medicament in aerosol form for inhalation therapy.
'monochlorotrifluoromethane (Freon l3) "ice In carrying out the invention it is contemplated that the non-toxic, liquid propellant shall be a fluorinated or a fluorochlorinated lower saturated aliphatic hydrocarbon, and preferably a halogenated alkane containing not more than 2 carbon atoms and at least 1 fluorine atom, or mixtures thereof. The preferred halogenated lower alkane compounds may be represented generally by the formula C H Cl F wherein an integer less than 3, n is an integer or zero, yis aninteger or zero, and z is an integer, such that n+y+z=2m+2. The propellants shall possess a boiling point of less than F. at 760 mm. pressure. Examples of the propellantsare dichlorodifiuoromethane (Freon 12), dichlorotetrafluoroethane (Freon 114) CCIF CClF trichloromonofluoromethane (Freon 11), dichloromonofiuoromethane (Freon 21), and Propellants with improved vapor pressure characteristics may be obtained by using certain mixtures of these compounds, e. g., Freon 11 and Freon 12, or Freon 12 and Freon 114, For example, dichlorodifluoromethane, which has a vapor pressure of about 70 pounds per square inch .gauge and 1,2-dichloro-1,1,2,2-tetrafluoroethane (Freon 114), with a vapor pressure of about -13 pounds per square inch. gauge at 70 F., may be mixed in various proportions to form a propellant having an intermediate vapor pressure which is well suited for use in relatively low pressure containers.
It is desired that the vapor pressure of the propellant employed shall itself be between about 25 and 65 pounds per square inch gauge at 70 F., and preferably between about 30 and 40 pounds per square inch gauge at that temperature. A one-component propellant defined'for use in thecomposition was found to give a'composition with gaugepressures in the rangeof 55to 65 pounds per square inch at 70 F., which are usable safely with metal containers. The two-component propellants, such as equalweight mixtures of Freon 12 and "Freon 11, were found to give gauge pressures in the range of 2 0 to 40 pounds per square inch at 70 F., which are usable safely with specially reinforced glass containers.
The medicament employed in a composition according to this invention can be one which is therapeutically ef fective when administered'by inhalation and which may be brought into stable solution in any of the above defined liquified propellants, if necessary, with the aid of a cosolvent and/ or stabilizing substance. One type of medicament which can be employed satisfactorily is the vasoconstrictive amines and their acid-addition salts. However, other types of medicaments, such :as hormones, enzymes, alkaloids, steroids, analgesics, broncho-dilators,. antihistamines, 'antitussives, anginal preparations, antibiotics and sulfonamides and synergistic combinations of these,v
may be employed successfully. Examples of the medicaments which may be employed in producing the compositions of this invention are: isoproterenol hydrochloride [u-(isopropylaminomethyl) protocatechuyl alcohol], phenylephrine, epinephrine, ephedrine, narcotine, codeine, atropine, ergotamine, scopolamine, colchicine, cortisone and alkyl nitrites, such'as amyl nitrite or octyl nitrite.
The co-solvent maybe any liquid substance which assists in. dissolving the medicament in the liquified propellant and which is chemically inert to the medicament in the sense that it does not promote the decomposition of this substance. Suitable co-solvents are intermediate in polarity between the propellant and the medicament.
The co-solvents have the property of being a solvent for the medicament and soluble in the propellants prescribed for use in this invention. The co-solvent beside being chemically inert toward the medicament, should benontoxic andwithout undesirable effects on inhalation in the amount present in the aersol produced. The co-solvent shall have as low a boiling point as possible and prefer-. ably not higher than 212 F. at atmospheric pressure. Examples of satisfactory co-solvents include non-toxic loweralcohols and eth ers, e. g., ethanol, diethyl ether, chloroform, mixtures of ethanol and wate r, and mixtures of chloroform and ethanol.
The stabilizers or anti-oxidants which .may be employed are stronger reducing agents than the medicament and which are non-toxic, such as the alkali-metal bisu'lfites (sodium bisulfite), alkali-metal ascorbates (sodium ascorbate), ascorbic acid, nordihydroguaiaretic acid, 2- tertiarybutyl-4-hyd'roxy anisole, 3-tertiarybutyl-4-hydroxy anisole, butylated hydroxytoluene' (sold under the trademark Tenox BHT), ethylhydro-caffeate, etc. It is normallynot necessary to employ -a stabilizer in an amount in excess'of 0.25% by-weight ofthe composition.
One of the important features of this invcntionisthe discovery that the components 'ofthe compositions must be present within certain critical proportions, as otherwise the benefits of the invention are not obtained. One of the most important characteristics of a spray product is the spray pattern. Spray pattern involves the delivery rate, the particle size distribution and the spray angle. The spray pattern is affected by mechanical factors, e. g., valve construction and orifice size and shape, and by the characteristics of the composition, e. g., viscosity, vapor pressure, type and percentage of propellant. For example, where less than the minimum proportion of pro= pellant is employed, thecomposition lack-suificient propellent force and consequently the'inadequate aerosolization of the medicament results in a particle size distribution which is not efiiciently absorbed in-the' bronchioles and alveoli. Where more than the allowable maximum proportion of propellant is employed, the composition may become unstable during storage and-the medicament may precipitate from the composition. Also, thecompositions may develop undesirably high pressures.
into an open container. The open container and its contents are then cooled, preferably to a temperature below the boiling point of the propellant to be employed. A temperature of 25 F. is usually satisfactory. A measured quantity of the liquified propellant which also has been cooled below its boiling point is then introduced into the container and mixed with the solution already present. The quantities of the components introduced into the container are calculated to provide the desired concentration of each in the final composition. Without permitting the temperature of the container and its contents to-rise above the boilingpoint of the propellant, the container is sealed with a closure equipped with asuitable dispensing valve arrangement. Upon warming to room temperature the Q mnts of the container are mixed by agitation of the containerto insure complete solution of the medicament. The sealed container is then ready to dispense the composition and provide the medicament naerosol form- In prder more clearly to disclose the nature of the present invention, the following examples illustrating compositions in accordance with the invention will now be described. ;It sohuld be understood, however, that this is done, solely by way of example and is intended neither to delineate the scope of the invention nor limit the. ambitofthe appended claims. .In the examples which follow, the processdescribed above was employed. In the cxampleswhich follow and throughout the specification, the quantities of material are expressed in termsof One I of the essential characteristics of the compositions of'this I invention is that the medicament shall remain'dissolved and uniformly dispersed throughout the composition. To this end a co-solvent is often necessary in order to maintain the medicament in the dissolved, uniformly dispersed state, both at the time the compositions are prepared and during normal periodsand conditions of storage.
While the proportions of components may varysomewhat depending upon the specific medicament and liquificd propellant employed, in general it has been found desirable that the liquid propellant constitute at least about 50% by weight of the total composition upward to about 90%. It is preferred that the propellant constitute between about 55% or 60% and 80% by weight of the total composition. The amount and constitution of the co-solvent is largely dependent upon the solubility characteristics of the medicament employed. In most cases it has been found that satisfactory results are obtained where the co-solvent constitutes between about 5% or 10% and 40%, and preferably between abont 20% and 40%'-- v we hto the t a .cQmP s t Qn- .lf to! to ch c -so n s s e hanol; is us th int rnattern ,is affected, resulting-in a wetsprayor stream rather thanan aerosol cloud. The amout of medicament shall generally constitute from about 0.1% to 20%, and preferably from about 0.1% to 2% by weight of the'composition. Desirably the propellant makes-upthe difference 'betwen the proportions of medicamennco-solvent, stabilizer and 100%.
"The novel compositions of the-invention maybe-prepared and containers filled with them by-means of-the following process:
Asuitable measured quantity-of the medicament-is mixed with, and dissolved in, a measured amountof the co-solvent. .A stabilizer, if desired,- is added. A- measured quantity-zof the resultingsolution isythea ntra used percentages bysweight of the total composition.
E le
P s-.4 1 Isoproterenol H61 0.25 ate 11.
thane? wer I fluerqmohaa wn 211-.-
Example 2 v Percent Isoproterenol HCl 2 0.25 Water V i 1. 5 Ethanol (absolute) 33.25 Dichlorotetrafluoroethane (Freon 114) 40 Dichlorodifluorornethane (Freon 12) 25.0
Example 3 I Percent Isoproterenol l ICl ate Ethan We Trichloromonotiuoromethane (Freon 1-1) Example 6 g 1 V H Percent Narcotine v 1 Water 0.65 Ethanol (absolute) a 12.35 Chloroform 20.6 Dichlorodifiuorornethane (Freon 12) i f-'3 4.8 Dichlorotetrafluoroethane (Freon 114) 30.6
' -Example 7 p t A Percent Nicotine "1 Ethanol 95% T 34 Dicblorodifiuoromethane (Freon 12) 25 Dichlorotetrafluoroethane (Freon 114) 40 g 100 --Example 8 i r Q 'Percent Isoproterenol HCl 0.25 Water 1 1.5 Ethanol (absolute) 33.25 Dichlorotetrafluoroethane-(Freon- -1 14) 45.5 Dichlorodifluor ometha'ne (Freon 12.) 19.5
Example 9 I Percent Octyl nitrite 0.1- Ethanol 95% p 20 Dichlorotetrafluoroethane (Freon 114) 49.2 Dichlorodifluoromethane (Freon '12) 30.7
Example 10 I I I P ercent Atropine 0.1 Ethanol 95% a 9.9 Dichlorodifluoromethane (Freon 12) 45 Dichlorotetrafluoroethane (Freon 114) 45 1 100 Example 11 i t Percent Octyl nitrite 0.1 Ethanol 95 9.9 Dichlorotetrafiuoroethane .(Freon 114) 55.4 Dichlorodifiuoromethane (Freon 12) 34.6
Y 100 Example 12 Percent O ctyl nitrite 0.1 Diethyl ether 14.9 'Dichlorotetrafluoroethane (Freon 114) 45 Dichlorodifluoromethane (Freon 12) 40 Other medicaments than those employed in the above examples may be used, such as ergot-amine, scopolamine,
" colchicine, cortisone, amyl nitrite, etc.
' is liquified and cooled at 25 F., added to the chilled concentrate and mixed in. Keeping it at the same temperature, the mixture is measured into the container to 4' be filled and the container is sealed with a closure equipped with a suit-able dispensing valve arrangement. An alternative process, known as pressure filling," is paricularly suitable where the closure employed has, a special valve construction, for'example, that of the type disclosed .in U. S. Patent 2,721,010, issued Octoberl8, 1955. Such a valve' construction permits dispensing a measured dose of medicament'in aerosol form;
It is desirable to enclose the composition in accordance with this invention in apressure-tight container having a suitable outlet valve secured in an opening in the top wall of the container. With the compositions of the invention the pressure rangeis such that it is permissible to use glass bottles instead of metal containers. The compositions and the bottles are characterized by a clear, sparkling appearancewith the advantage that it is easy to observe when the'container is nearly empty. It is recommended for added safety that the glass bottles be coated with a plastic film, preferably clear. 'Aldip-tube of suitable material may be connected with the opening containing the valve arrangement and extendingfto the bottom of the container or an inverted system without a dip-tube may be'-used.-- Upon opening the valve the composition is expelled through the opening in the form of a fine stream to form an aerosol of the medicament. Toaccomplish suitable aerosolization of the medicatnent the opening is desirably constructed to provide a small orifice so as to expel a fine spray of the composition., The container just described is typical of thesecalled aerosol bomb. One typical form of device which iseminently satisfactory for dispensing accurately measured quantities of the medicament in a suitable aerosol form and insuring eflective administration is that disclosed in our copending' application entitled, Aerosol Dispensing Apparatus, Serial No. 572,965,--filed concurrently with this application. I "The terms and expressions which we have employed are used as terms-of description and not of limitation, and we have no intention, in the use of suchterms and expressions, of excluding any equivalents of the features shown and described or portions thereof, but recognize that various modifications are possible within the scop of the invention claimed.
, .What is claimed is: a
1. A self-propelling pharmaceutical composition capable of providing a medicament in aerosol formsuitable for inhalation therapy, comprising as the medicament a water-soluble acid-addition salt of a bronchodi lator amine selected from the class consisting of isoproterenol and epinephrine, said medicament comprising between about 0.1% and 2% of the composition, as a co solvent for said medicament, an aqueous ethanol mixture in an amount comprising between about 20% to 40% of the composition, the water in said cosolvent comprising between about 1.5% and 2% 'of the total com'-' position, and as a liquefied non-toxic propellant componut 21 halogenated lower alkane containing at least 1 fluorine atom and not more than 2 carbon atoms and having a vapor pressure of between about 20 and 65 pounds per square inch gauge at F., said liquefied propellantfcomponent comprising substantially the re mainder of the composition.
2.- A self-propelling pharmaceutical composition as defined by claim 1, wherein the liquefied non-toxic propellantcomponent comprises a mixture of said halogenated lower alkanes.
3. A self-propelling pharmaceutical composition as defined by claim 1, wherein the liquefied non-toxic propellant component has a vapor pressure of between about a 20 and 40 pounds per square inch gauge at 70 F.
4. A self-propelling pharmaceutical composition as defined by claim I, wherein the liquefied non-toxic propellant component is selected from the group consisting of dichlorodifluoromethane and a mixture of dichlorodifiuoromethane and dichlorotetrafiuoroethane.
'5. A self-propelling pharmaceutical composition as deinedby c im. 1, whe e h m c m compr se a water s'oliibleiacid addition salt of epinephrine.
Aseiep o onia pharmaceutical composition as defined by claim 1, wherein the medicament comprises isoproterenol hydrochloride.
,8 A s lfr e lin ha a tica c m osi as. efi y fs i .1. he e n th h q sam nt om ses epinephrine hydrochloride.
se -swellin Ph r aceut ca o po t on si efined by claim '1, containing about 0.2% isoproterenol hydrochloride, about 2% wate about 37.8% ethanol, 3 91 .39 li uefied tsi hls qmh ofluorom hane. and shq li e i d. is lomdiflu sm th .A- Ql -Pmps in pharm seu l mp sition as defined'by claim 1, containing about 0.25% epinephrine, about 0.5%,oj a 3% .normal solution ofhydrochloric acid, about 0.15% ascorbic acid, about; 1% a ditional-water, about 33. 1%, ethanol, about 25% liquefiedv dichlorodisfiuoromethane, and about 40% liquefied ,dichlorotetra: fluoroethane.
11 A self-propelling pharmaceutical composition as defined by claim .1 containing about 0.25% ,isoprotera enol hydrochloride, about-1.5% water, about 33.25%- ethanol, and the remainder being a liquefied'non-toxie propellant as ,defi ne d by claim 1.
12. Asel-f-propelling pharmaceutical composition as definedby claim 11, containing about 0.25%l.isoproter-. enol hydrochloride, about 1.5% water, about "33.25% ethanol, and the remainder being liquefied dichlorodifluoromethane. i 13. A self-propelling pharmaceutical composition as defined by claim 11, containing about 0.25% isoproterenol hydrochloride, about 1.5 water, about 33.25% ethanol, about 40% liquefied dichlorotetrafiuoroethane, and-about 25% liquefied dichlorodifluoromethane. V
14. A package comprising a pressure-tight container having a valve-controlled opening and containing a selfpropelling pharmaceutical composition capable of providing a medicament in aerosol form suitable forinhal-ation therapy, comprising as a medicament a water-soluble acid-addition salt ofa bronchodilator' amine selected from the. class consisting of. isoproterenol and epinephrine,- said medicament comprising between about 0.1% and 2% of the composition, as. a .cosolvent-for said medicament an aqueous ethanol mixture. in an. amount comprising- -betwee about 20%. and 40% of the composition, the waterin said cosolvent comprising between about 1.5% and 2% of the total. composition, and as a liquefiedinontoxic propellant component a halogenated lower allgane containing at least '1 fluorine atom and not more that-n2 carbon atoms and. having a vapor pressure ofbetween abqutZO: and 65 pounds per square inch gauge at- 70" =F.',
8 said liquefied propellant component comprising substantia l lythe remainder of the composition.
15. A method oi producing a measured dose ofimedicament in aerosol form suitable for inhalation therapy whi omprise f rm n a q d mposition oira' msdis mentqnthetorm o a atqrs luhleaci d ition altof abronchodilatoramine selected from the class consisting otisoproterenol and epinephrine, said medicamom. comprising between about 0.1% and 2% of the composition, said medicament being dissolved ina mixture of a co-solvent and a liquefied non-toxic propellant component, said co-solvent comprising an aqueous ethanol gniggtpre i n an amount comprising between about 2 1 and 49% oi the total. c mpos the Waterfih said nqns9lve n t comprising between about l.5'%.wand'2%' or the total composition, said liquefied non-toxic; propellant component comprising a halogenated lower alkane containing at least 1 fluorine atom and not more than 2 carbon atoms and having a--.v-ap,or pressure of between ab9u-t'20 and pounds per square inch gauge at F., said liquefied propellant component comprising substan-v a ly e .remainder ofthe. composition,v .and dispensing he. l iq isl .qq l position. from. a. pressure-tight. container through a control valve for-self-propelled delivery in the f rm of an. a lQS01' l'QSU1l1l1g from the rapidvaporization of...the propellant.
References Cited in thefile 'of this patent UNITED STATES PATENTS 2,232,976- Fox Nov. 26,1240,
Fulton: Propellents for Low-Pressure Liquefied Gas Aerosols, Ind. and Eng. Chem, vol. 40, No. 4, April 1948, pp. 699 and 700.
Fulton: Germicidal Aerosols, Soap and Sanitary Chemicals, May 1948, pp. -127, 157 and 1 59..
Mina-z Glass-Aerosols for Cosmetics, Amer. Peri. and'EsscOil Rev- Iune 1954, pp. 429-31;
Downing:- Formulation of- Aerosol Products, Soap and; Sanitary Chem., September 1953, pp. 142, 143, 145, 147; 149, 153, 155, 177 and 178.
U. S. Disp., 25th Ed., J; B. Lippincott Co., pp. 38 and 39,- Philadelphia, Pa.
Drugand Cos. Ind., vol. 65, No. 4, October 1949,. pp, 396-98-and- 470-73. I
New'and- Non-oificial Remedies, J. B; Lippincott Co.,v Philadelphia, Pa., 1955, pp. 225-227;
Merck Index, 6th ed., Merck and Co., Inc., 1952, pp. 72, 73, 387-89, 664 and, 674-75..

Claims (1)

1. A SELF-PROPELLING PHARMACEUTICAL COMPOSITION CAPABLE OF PROVIDING A MEDICAMENT IN AERSOL FROM SUITABLE FOR INHALATION THERAPY, COMPRISING AS THE MEDICANENT A WATER-SOLUBLE ACID-ADDITON SALT OF A BRONCHODILATOR AMINE SELECTED FROM THE CLASS CONSISTING OF ISOPROTERENOL AND EPINEPHRINE, SAID MEDICAMENT COMPRISING BETWEEN ABOUT 0.1% AND 2% OF THE COMPOSITION, AS A COSOLVENT FOR SAID MEDICAMENT, AN AQUEOUS ETHANOL MIXTURE IN AN AMOUNT COMPRISING BETWEEN ABOUT 20% TO 40% OF THE COMPOSITION, THE WATER IN SAID COSOLVENT COMPRISING BETWEEN ABOUT 1.5% AND 2% OF THE TOTAL COMPOSITION, AND AS A LIQUEFIED NON-TOXIC PROPELLANT COMPONENT A HALOGENATED LOWER ALKANE CONTAINING AT LEAST 1 FLUORINE ATOM AND NOT MORE THAN 2 CARBON ATOMS AND HAVING A VAPOR PRESSURE OF BETWEEN ABOUT 20 AND 65 POUNDS PER SQUARE INCH GAUGE AT 70* F., SAID LIQUEFIED PROPELLANT COMPONENT COMPRISING SUBSTANTIALLY THE REMAINDER OF THE COMPOSITION.
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Cited By (133)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3039929A (en) * 1960-03-17 1962-06-19 Abbott Lab Stable isoproteronol compositions
US3039928A (en) * 1960-03-17 1962-06-19 Abbott Lab Stable aqueous isoproteronol compositions
US3050443A (en) * 1960-02-16 1962-08-21 James F Schuyler Headache remedy containing ammonia
US3051621A (en) * 1959-10-22 1962-08-28 Grove Lab Inc Gel composition, pressurized container with same, and method of preparation
US3088874A (en) * 1960-05-23 1963-05-07 Union Carbide Corp Powder aerosol
US3155574A (en) * 1962-05-24 1964-11-03 Revlon Aerosol composition
US3169095A (en) * 1962-10-30 1965-02-09 Rexall Drug Chemical Self-propelling powder-dispensing compositions
US3282781A (en) * 1960-11-25 1966-11-01 Merck & Co Inc Inhalant compositions
US3341604A (en) * 1963-01-28 1967-09-12 Exxon Research Engineering Co Color stable ketone solvent composition
US3710782A (en) * 1969-10-01 1973-01-16 Hauser Res And Eng Co Method of treating human skin with a composition for electromedical applications
DE2703119A1 (en) * 1976-01-30 1977-08-04 Fisons Ltd SODIUMCROMOGLYCAT WITH LESS THAN 5% WATER AND THIS COMPREHENSIVE PHARMACEUTICAL PREPARATIONS
DE2831419A1 (en) * 1977-07-19 1979-02-01 Fisons Ltd Aerosol compsn., pref. contg. fine medicament
US4352789A (en) * 1980-03-17 1982-10-05 Minnesota Mining And Manufacturing Company Aerosol compositions containing finely divided solid materials
EP0148748A2 (en) * 1984-01-09 1985-07-17 Ab Leo Improved snuff and preparation thereof
US4576949A (en) * 1984-05-07 1986-03-18 The Upjohn Company Use of 5,6,7,8-tetrahydroquinolines and 5,6-dihydropyrindines as leukotriene and lipoxygenase inhibitors and the novel 3-substituted compounds therein
EP0213108A2 (en) * 1985-06-26 1987-03-04 Kurt Dr. Burghart Pharmaceutical preparation containing an antihypotonic as the active agent
FR2625677A1 (en) * 1988-01-07 1989-07-13 Cosnier Alain Medicinal composition intended for administration in aerosol form
US4919919A (en) * 1987-09-30 1990-04-24 Nippon Kayaku Kabushiki Kaisha Nitroglycerin spray
WO1992005781A1 (en) * 1990-09-28 1992-04-16 The Procter & Gamble Company Composition containing ephedrine base and alkyl salicylate for the delivery of ephedrine base in vapor form
US5118494A (en) * 1990-03-23 1992-06-02 Minnesota Mining And Manufacturing Company Use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations
US5225183A (en) * 1988-12-06 1993-07-06 Riker Laboratories, Inc. Medicinal aerosol formulations
US5292884A (en) * 1991-10-31 1994-03-08 Biomide Investment Limited Partnership Cyclic hydroxamic acids
WO1994013262A1 (en) * 1992-12-09 1994-06-23 Boehringer Ingelheim Pharmaceuticals, Inc. Stabilized medicinal aerosol solution formulations
US5439670A (en) * 1989-11-28 1995-08-08 Riker Laboratories, Inc. Medicinal aerosol formulations
EP0703216A1 (en) 1994-09-20 1996-03-27 Ono Pharmaceutical Co., Ltd. Amidinophenol derivatives as protease inhibitors
US5514713A (en) * 1993-12-03 1996-05-07 Ono Pharmaceutical Co., Ltd. Amidinophenol derivatives
US5534536A (en) * 1993-08-24 1996-07-09 Ono Pharmaceuticals Co. Ltd. Fused phenol derivatives
WO1996033913A1 (en) * 1995-04-28 1996-10-31 Great Lakes Chemical Corporation Novel uses of heptafluoropropane
EP0757037A2 (en) 1995-07-28 1997-02-05 Ono Pharmaceutical Co., Ltd. Sulfonylamino acid derivatives as metalloproteinase inhibitors
US5653962A (en) * 1991-12-12 1997-08-05 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicaments
US5658549A (en) * 1991-12-12 1997-08-19 Glaxo Group Limited Aerosol formulations containing propellant 134a and fluticasone propionate
US5674472A (en) * 1991-12-12 1997-10-07 Glaxo Group Limited Canisters containing aerosol formulations containing P134a and fluticasone propionate
US5674471A (en) * 1991-12-12 1997-10-07 Glaxo Group Limited Aerosol formulations containing P134a and salbutamol
US5736124A (en) * 1991-12-12 1998-04-07 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
US5744123A (en) * 1991-12-12 1998-04-28 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicaments
US5766573A (en) * 1988-12-06 1998-06-16 Riker Laboratories, Inc. Medicinal aerosol formulations
US5776433A (en) * 1993-12-20 1998-07-07 Minnesota Mining And Manufacturing Company Flunisolide aerosol formulations
US5776432A (en) * 1990-10-18 1998-07-07 Minnesota Mining And Manufacturing Company Beclomethasone solution aerosol formulations
US5785952A (en) * 1990-11-09 1998-07-28 Glaxo Group Limited Aerosol medicament formulation having a surface coating of surfactant
US5817293A (en) * 1991-12-12 1998-10-06 Glaxo Group Limited Canister containing aerosol formulations containing P134a and particulate medicaments
US5840213A (en) * 1995-04-28 1998-11-24 Great Lakes Chemical Corporation Uses of heptafluoropropane
US5861268A (en) * 1996-05-23 1999-01-19 Biomide Investment Limited Partnership Method for induction of tumor cell apoptosis with chemical inhibitors targeted to 12-lipoxygenase
US5891419A (en) * 1997-04-21 1999-04-06 Aeropharm Technology Limited Environmentally safe flunisolide aerosol formulations for oral inhalation
US5891420A (en) * 1997-04-21 1999-04-06 Aeropharm Technology Limited Environmentally safe triancinolone acetonide aerosol formulations for oral inhalation
US5916540A (en) * 1994-10-24 1999-06-29 Glaxo Group Limited Aerosol formulations containing P134A and/or P227 and particulate medicament
US5919435A (en) * 1990-11-09 1999-07-06 Glaxo Group Limited Aerosol formulation containing a particulate medicament
US5922306A (en) * 1991-12-12 1999-07-13 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
US6022893A (en) * 1995-08-08 2000-02-08 Ono Pharmaceutical Co., Ltd. Hydroxamic acid derivatives
US6054488A (en) * 1996-06-11 2000-04-25 3M Innovative Properties Company Medicinal aerosol formulations of formoterol
AU721920B2 (en) * 1996-08-01 2000-07-20 Norton Healthcare Limited Aerosol formulations
US6129905A (en) * 1997-04-21 2000-10-10 Aeropharm Technology, Inc. Aerosol formulations containing a sugar as a dispersant
US6136294A (en) * 1998-09-22 2000-10-24 Aeropharm Technology Inc. Amino acid stabilized medical aerosol formulation
US6416743B1 (en) 1991-06-10 2002-07-09 Schering Corporation Aerosol formulations of albuterol and 1,1,1,2-tetrafluoroethane
US6458338B1 (en) 1998-09-22 2002-10-01 Aeropharm Technology Incorporated Amino acid stabilized medicinal aerosol formulations
US6461591B1 (en) 1997-02-05 2002-10-08 Jago Research Ag Medical aerosol formulations
US6475467B1 (en) 1998-08-04 2002-11-05 Jago Research Ag Medicinal aerosol formulations
US20030089369A1 (en) * 1998-11-25 2003-05-15 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
US20030096802A1 (en) * 1993-06-01 2003-05-22 Ono Pharmaceutical Co., Ltd. Pentanoic acid derivatives
US6585958B1 (en) 1998-07-24 2003-07-01 Jago Research Ag Medicinal aerosol formulations
US20030223939A1 (en) * 2002-04-17 2003-12-04 Andreas Kordikowski Particulate materials
US20040033201A1 (en) * 1999-06-18 2004-02-19 3M Innovative Properties Company Process for making chemically stable C-17/21 OH 20-ketosteroid aerosol products
US20040062720A1 (en) * 1997-06-13 2004-04-01 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
WO2004031118A1 (en) 2002-10-03 2004-04-15 Ono Pharmaceutical Co., Ltd. Lpa receptor antagonists
WO2004032965A1 (en) 2002-10-10 2004-04-22 Ono Pharmaceutical Co., Ltd. Endogenous repair factor production promoters
US6743413B1 (en) 1991-12-18 2004-06-01 3M Company Suspension aerosol formulations
US20050069918A1 (en) * 2003-05-29 2005-03-31 Francois Claret JAB1 as a prognostic marker and a therapeutic target for human cancer
US20050107306A1 (en) * 2003-05-16 2005-05-19 Barr Philip J. Treatment of respiratory disease associated with matrix metalloproteases by inhalation of synthetic matrix metalloprotease inhibitors
WO2005063704A1 (en) 2003-12-25 2005-07-14 Ono Pharmaceutical Co., Ltd. Azetidine ring compounds and drugs comprising the same
US20050175680A1 (en) * 2002-06-25 2005-08-11 Acrux Dds Pty Ltd. Transdermal delivery rate control using amorphous pharmaceutical compositions
US20050181032A1 (en) * 2002-06-25 2005-08-18 Acrux Dds Pty Ltd. Metastable pharmaceutical compositions
US20050186141A1 (en) * 2002-06-25 2005-08-25 Acrux Dds Pty Ltd. Transdermal aerosol compositions
US20060018840A1 (en) * 2004-06-28 2006-01-26 Nektar Therapeutics Aerosolizable formulation comprising nicotine
US20060110328A1 (en) * 2004-11-24 2006-05-25 Cagle Gerald D Method of delivering nasal spray
US20060128810A1 (en) * 2002-10-10 2006-06-15 Kyoto University Remedies for allergic diseases
US7101534B1 (en) 1991-12-18 2006-09-05 3M Innovative Properties Company Suspension aerosol formulations
US7105152B1 (en) 1991-12-18 2006-09-12 3M Innovative Properties Company Suspension aerosol formulations
US20070021323A1 (en) * 1997-05-27 2007-01-25 Government of the USA, represented by the Secretary, Use of a nitroxide or a prodrug thereof in the prophylactic and therapeutic treatment of cancer
US20070065370A1 (en) * 1990-02-03 2007-03-22 Boehringer Ingelheim Kg Suspension aerosol formulationis of pharmaceutical products
US20070071803A1 (en) * 1996-02-19 2007-03-29 Acrux Dds Pty Ltd Dermal penetration enhancers and drug delivery systems involving same
WO2007049771A1 (en) 2005-10-28 2007-05-03 Ono Pharmaceutical Co., Ltd. Compound containing basic group and use thereof
WO2007069565A1 (en) 2005-12-12 2007-06-21 Ono Pharmaceutical Co., Ltd. Bicyclic heterocyclic compound
WO2007069671A1 (en) 2005-12-15 2007-06-21 Ono Pharmaceutical Co., Ltd. Bicyclic heterocyclic compound
US20070253913A1 (en) * 2003-09-10 2007-11-01 Nahed Mohsen Aerosol formulations for delivery of dihydroergotamine to the systemic circulation via pulmonary inhalation
US20080064674A1 (en) * 2003-10-20 2008-03-13 Schering Corporation Pharmaceutical Compositions
WO2008136377A1 (en) 2007-04-26 2008-11-13 Ono Pharmaceutical Co., Ltd. Bicyclic heterocyclic compound
US20080287451A1 (en) * 2007-02-11 2008-11-20 Cook Robert O Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile
US20090191134A1 (en) * 2006-06-12 2009-07-30 Medispray Laboratoriespvt. Ltd. Stable aerosol pharmaceutical formulations
EP2085071A1 (en) 2008-02-01 2009-08-05 Infectopharm Arzneimittel und Consilium GmbH Orally or nasally administrable preparations containing epinephrine with improved characteristics
US20100037890A1 (en) * 2005-05-18 2010-02-18 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US20100087416A1 (en) * 2008-10-07 2010-04-08 Mpex Pharmaceuticals, Inc. Aerosol fluoroquinolone formulations for improved pharmacokinetics
US20100087386A1 (en) * 2008-10-07 2010-04-08 Mpex Pharmaceuticals, Inc. Topical use of levofloxacin for reducing lung inflammation
EP2206698A1 (en) 2008-12-22 2010-07-14 ONO Pharmaceutical Co., Ltd. Ethynylindole compounds
EP2243493A1 (en) 2002-07-03 2010-10-27 Ono Pharmaceutical Co., Ltd. Immunopotentiative composition
EP2253642A1 (en) 1997-12-26 2010-11-24 ONO Pharmaceutical Co., Ltd. Polypeptides, cDNAs encoding the same and utilization thereof
EP2255829A2 (en) 2001-07-23 2010-12-01 Ono Pharmaceutical Co., Ltd. Pharmaceutical composition for treatment of diseases associated with decrease in bone mass comprising EP4 agonist as active ingredient
WO2010147133A1 (en) 2009-06-17 2010-12-23 小野薬品工業株式会社 Novel imidazopyridine compound
EP2270051A2 (en) 2003-01-23 2011-01-05 Ono Pharmaceutical Co., Ltd. Antibody specific for human PD-1 and CD3
EP2281818A1 (en) 2002-02-19 2011-02-09 Ono Pharmaceutical Co., Ltd. Fused pyridazine derivative compounds and drugs containing these compounds as the active ingredient
WO2011066537A1 (en) 2009-11-30 2011-06-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Nitroxide therapy for the treatment of von hippel - lindau disease (vhl) and renal clear cell carcinoma (rcc)
US20110171141A1 (en) * 2009-06-26 2011-07-14 Kellerman Donald J Administration of dihydroergotamine mesylate particles using a metered dose inhaler
EP2364982A1 (en) 2003-04-18 2011-09-14 ONO Pharmaceutical Co., Ltd. Spiro-piperidine compounds as chemokine receptor antagonists and medicinal use thereof
EP2385040A1 (en) 2003-03-14 2011-11-09 ONO Pharmaceutical Co., Ltd. Nitrogen-containing heterocyclic derivatives and drugs containing the same as the active ingredient
US8080236B2 (en) 2002-04-17 2011-12-20 Nektar Therapeutics Uk, Ltd Particulate materials
WO2011162222A1 (en) 2010-06-21 2011-12-29 小野薬品工業株式会社 Novel crystalline forms of 4,4'-[4-fluoro-7-({4-[4-(3-fluoro-2-methylphenyl)butoxy]phenyl}ethynyl)-2-methyl-1h-indole-1,3-diyl]dibutanoic acid, 4,4'-[2-methyl-7-({4-[4-(pentafluorophenyl)butoxy]phenyl}ethynyl)-1h-indole-1,3-diyl]dibutanoic acid, and 4,4'-[4-fluoro-2-methyl-7-({4-[4-(2,3,4,6-tetrafluorophenyl)butoxy]phenyl}ethynyl)-1h-indole-1,3-diyl]dibutanoic acid
EP2422814A1 (en) 2003-07-25 2012-02-29 Ono Pharmaceutical Co., Ltd. Remedy for cartilage-related diseases
WO2012074069A1 (en) 2010-12-02 2012-06-07 小野薬品工業株式会社 Novel compound and medical use thereof
EP2465538A2 (en) 2004-10-21 2012-06-20 Ono Pharmaceutical Co., Ltd. Use of immunesuppressant receptor
EP2481732A1 (en) 2003-09-01 2012-08-01 Ono Pharmaceutical Co., Ltd. Condensed ring compound and use thereof
WO2012106382A1 (en) 2011-01-31 2012-08-09 Genoa Pharmaceuticals, Inc. Aerosol pirfenidone and pyridone analog compounds and uses thereof
WO2012127885A1 (en) 2011-03-18 2012-09-27 小野薬品工業株式会社 Tetrahydrocarboline derivative
EP2508204A2 (en) 2002-06-26 2012-10-10 Ono Pharmaceutical Co., Ltd. Remedies for diseases caused by vascular contraction or dilation
US20120316246A1 (en) * 2005-06-17 2012-12-13 Fahl William E Topical vasoconstrictor preparations and methods for protecting cells during cancer chemotherapy and radiotherapy
EP2594272A2 (en) 2005-05-18 2013-05-22 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
WO2013161919A1 (en) 2012-04-26 2013-10-31 小野薬品工業株式会社 Trk-INHIBITING COMPOUND
WO2014129431A1 (en) 2013-02-19 2014-08-28 小野薬品工業株式会社 Trk-INHIBITING COMPOUND
EP2883865A1 (en) 2003-08-29 2015-06-17 Ono Pharmaceutical Co., Ltd. Compound capable of binding S1P receptor and pharmaceutical use thereof
WO2015115673A1 (en) 2014-01-31 2015-08-06 Ono Pharmaceutical Co., Ltd. Fused imidazole compounds
US9522143B2 (en) 2005-02-02 2016-12-20 Mitos Pharmaceuticals, Inc. Nitroxides for use in treating or preventing diabetes and obesity
US9700564B2 (en) 2009-09-04 2017-07-11 Horizon Orphan Llc Use of aerosolized levofloxacin for treating cystic fibrosis
WO2018101309A1 (en) 2016-11-30 2018-06-07 大日本住友製薬株式会社 Wt1 helper peptide, and combination of said peptide and cancer antigen peptide conjugate
US10028966B2 (en) 2014-01-10 2018-07-24 Avalyn Pharma Inc. Aerosol pirfenidone and pyridone analog compounds and uses thereof
WO2018181648A1 (en) 2017-03-30 2018-10-04 大日本住友製薬株式会社 Wt1 cancer antigen peptide and peptide conjugate body containing same
WO2019049891A1 (en) 2017-09-06 2019-03-14 小野薬品工業株式会社 METHOD FOR TREATING CANCER BY COMBINATION OF Trk INHIBITOR AND KINASE INHIBITOR
WO2019230919A1 (en) 2018-05-31 2019-12-05 小野薬品工業株式会社 Biomarker for judging efficacy of immune checkpoint inhibitor
WO2020075790A1 (en) 2018-10-11 2020-04-16 小野薬品工業株式会社 Sting-agonist compound
WO2021025031A1 (en) 2019-08-05 2021-02-11 小野薬品工業株式会社 Biomarker for accessing efficacy of immune checkpoint inhibitor
EP3782604A1 (en) 2013-07-31 2021-02-24 Windward Pharma, Inc. Aerosol tyrosine kinase inhibitor compounds and uses thereof
WO2021107125A1 (en) 2019-11-29 2021-06-03 小野薬品工業株式会社 Compound having lysophosphatidic acid receptor agonistic activity and pharmaceutical use of said compound
WO2021205631A1 (en) 2020-04-10 2021-10-14 小野薬品工業株式会社 Sting agonistic compound
WO2021230247A1 (en) 2020-05-12 2021-11-18 大日本住友製薬株式会社 Pharmaceutical composition for treating cancer
WO2022240897A1 (en) 2021-05-10 2022-11-17 Sepelo Therapeutics, Llc Pharmaceutical composition comprising delafloxacin for administration into the lung
WO2022251679A1 (en) 2021-05-27 2022-12-01 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Nitroxide radicals for use as antiviral treatment for coronavirus infection
WO2023028364A1 (en) 2021-08-27 2023-03-02 Sepelo Therapeutics, Llc Targeted compositions and uses therof

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE68915203T2 (en) * 1988-03-22 1994-09-22 Fisons Plc Pharmaceutical blends.

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2222976A (en) * 1937-11-15 1940-11-26 Sharp & Dohme Inc Nasal drops
US2728495A (en) * 1951-04-19 1955-12-27 Little Inc A Liquid dispensing device and composition therefor

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2222976A (en) * 1937-11-15 1940-11-26 Sharp & Dohme Inc Nasal drops
US2728495A (en) * 1951-04-19 1955-12-27 Little Inc A Liquid dispensing device and composition therefor

Cited By (238)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3051621A (en) * 1959-10-22 1962-08-28 Grove Lab Inc Gel composition, pressurized container with same, and method of preparation
US3050443A (en) * 1960-02-16 1962-08-21 James F Schuyler Headache remedy containing ammonia
US3039929A (en) * 1960-03-17 1962-06-19 Abbott Lab Stable isoproteronol compositions
US3039928A (en) * 1960-03-17 1962-06-19 Abbott Lab Stable aqueous isoproteronol compositions
US3088874A (en) * 1960-05-23 1963-05-07 Union Carbide Corp Powder aerosol
US3282781A (en) * 1960-11-25 1966-11-01 Merck & Co Inc Inhalant compositions
US3155574A (en) * 1962-05-24 1964-11-03 Revlon Aerosol composition
US3169095A (en) * 1962-10-30 1965-02-09 Rexall Drug Chemical Self-propelling powder-dispensing compositions
US3341604A (en) * 1963-01-28 1967-09-12 Exxon Research Engineering Co Color stable ketone solvent composition
US3710782A (en) * 1969-10-01 1973-01-16 Hauser Res And Eng Co Method of treating human skin with a composition for electromedical applications
DE2703119A1 (en) * 1976-01-30 1977-08-04 Fisons Ltd SODIUMCROMOGLYCAT WITH LESS THAN 5% WATER AND THIS COMPREHENSIVE PHARMACEUTICAL PREPARATIONS
DE2831419A1 (en) * 1977-07-19 1979-02-01 Fisons Ltd Aerosol compsn., pref. contg. fine medicament
US4352789A (en) * 1980-03-17 1982-10-05 Minnesota Mining And Manufacturing Company Aerosol compositions containing finely divided solid materials
EP0148748A2 (en) * 1984-01-09 1985-07-17 Ab Leo Improved snuff and preparation thereof
EP0148748A3 (en) * 1984-01-09 1988-01-07 Ab Leo Improved snuff and preparation thereof
US4576949A (en) * 1984-05-07 1986-03-18 The Upjohn Company Use of 5,6,7,8-tetrahydroquinolines and 5,6-dihydropyrindines as leukotriene and lipoxygenase inhibitors and the novel 3-substituted compounds therein
EP0213108A2 (en) * 1985-06-26 1987-03-04 Kurt Dr. Burghart Pharmaceutical preparation containing an antihypotonic as the active agent
EP0213108A3 (en) * 1985-06-26 1987-07-15 Kurt Dr. Burghart Pharmaceutical preparation containing an antihypotonic as the active agent
US4919919A (en) * 1987-09-30 1990-04-24 Nippon Kayaku Kabushiki Kaisha Nitroglycerin spray
FR2625677A1 (en) * 1988-01-07 1989-07-13 Cosnier Alain Medicinal composition intended for administration in aerosol form
US5720940A (en) * 1988-12-06 1998-02-24 Riker Laboratories, Inc. Medicinal aerosol formulations
US5225183A (en) * 1988-12-06 1993-07-06 Riker Laboratories, Inc. Medicinal aerosol formulations
US5674473A (en) * 1988-12-06 1997-10-07 Riker Laboratories, Inc. Medicinal aerosol formulations
US5766573A (en) * 1988-12-06 1998-06-16 Riker Laboratories, Inc. Medicinal aerosol formulations
US5695743A (en) * 1988-12-06 1997-12-09 Riker Laboratories, Inc. Medicinal aerosol formulations
US5683677A (en) * 1988-12-06 1997-11-04 Riker Laboratories, Inc. Medicinal aerosol formulations
US6352684B1 (en) 1988-12-06 2002-03-05 Riker Laboratories Inc. CRC-free medicinal aerosol formulations of 1,1,1,2-tetrafluoroethane (134A) with polar adjuvant
US5605674A (en) * 1988-12-06 1997-02-25 Riker Laboratories, Inc. Medicinal aerosol formulations
US5681545A (en) * 1988-12-06 1997-10-28 Riker Laboratories, Inc. Medicinal aerosol formulations
US5439670A (en) * 1989-11-28 1995-08-08 Riker Laboratories, Inc. Medicinal aerosol formulations
US20090104127A1 (en) * 1990-02-03 2009-04-23 Boehringer Ingelheim Kg Suspension aerosol formulations of pharmaceutical products
US20110014134A1 (en) * 1990-02-03 2011-01-20 Boehringer Ingelheim Kg Suspension aerosol formulations of pharmaceutical products
US20070065370A1 (en) * 1990-02-03 2007-03-22 Boehringer Ingelheim Kg Suspension aerosol formulationis of pharmaceutical products
US5118494A (en) * 1990-03-23 1992-06-02 Minnesota Mining And Manufacturing Company Use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations
US5175152A (en) * 1990-09-28 1992-12-29 Singh Nikhilesh N Composition containing ephedrine base and alkyl salicylate for the delivery of ephedrine base in vapor form
WO1992005781A1 (en) * 1990-09-28 1992-04-16 The Procter & Gamble Company Composition containing ephedrine base and alkyl salicylate for the delivery of ephedrine base in vapor form
US6346232B1 (en) 1990-10-18 2002-02-12 3M Innovative Properties Company Method of forming conductive lines
US5776432A (en) * 1990-10-18 1998-07-07 Minnesota Mining And Manufacturing Company Beclomethasone solution aerosol formulations
US5785952A (en) * 1990-11-09 1998-07-28 Glaxo Group Limited Aerosol medicament formulation having a surface coating of surfactant
US6306368B1 (en) 1990-11-09 2001-10-23 Glaxo Group Limited Aerosol formulation containing a particulate medicament
US5919435A (en) * 1990-11-09 1999-07-06 Glaxo Group Limited Aerosol formulation containing a particulate medicament
US6503482B1 (en) 1991-06-10 2003-01-07 Schering Corporation Non-chlorofluorocarbon aerosol formulations
US6416743B1 (en) 1991-06-10 2002-07-09 Schering Corporation Aerosol formulations of albuterol and 1,1,1,2-tetrafluoroethane
US5292884A (en) * 1991-10-31 1994-03-08 Biomide Investment Limited Partnership Cyclic hydroxamic acids
US20030165437A1 (en) * 1991-12-12 2003-09-04 Glaxo Group Limited Aerosos formulations containing P134a and particulate medicament
US20050207991A1 (en) * 1991-12-12 2005-09-22 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
US5683676A (en) * 1991-12-12 1997-11-04 Glaxo Group Limited Canister containing aerosol formulations containing P134a and particulate medicaments
US6303103B1 (en) 1991-12-12 2001-10-16 Glaxo Group Limited Aerosols containing salmeterol xinafoate and an anticholinergic medicament
US20050089477A1 (en) * 1991-12-12 2005-04-28 Glaxo Group Limited Medicaments
US5736124A (en) * 1991-12-12 1998-04-07 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
US5744123A (en) * 1991-12-12 1998-04-28 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicaments
US6893628B2 (en) 1991-12-12 2005-05-17 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
US6251368B1 (en) 1991-12-12 2001-06-26 Glaxo Group Limited Pharmaceutical aerosol formulation containing a particulate medicament, a propellant and substantially free of a surfactant
US20030198600A1 (en) * 1991-12-12 2003-10-23 Glaxo Group Limited Aerosol formulation containing particulate formoterol, propellant and polar cosolvent
US6238647B1 (en) 1991-12-12 2001-05-29 Glaxo Group Limited Aerosol formulations containing salmeterol xinafoate, an anticholinergic agent and tetrafluoroethane
US6306369B1 (en) 1991-12-12 2001-10-23 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
US5817293A (en) * 1991-12-12 1998-10-06 Glaxo Group Limited Canister containing aerosol formulations containing P134a and particulate medicaments
US5674472A (en) * 1991-12-12 1997-10-07 Glaxo Group Limited Canisters containing aerosol formulations containing P134a and fluticasone propionate
US20030143163A1 (en) * 1991-12-12 2003-07-31 Glaxo Group Limited Medicaments
US6919069B2 (en) 1991-12-12 2005-07-19 Glaxo Group Limited Aerosol formulation containing particulate formoterol, propellant and polar cosolvent
US20090188491A1 (en) * 1991-12-12 2009-07-30 Glaxo Group Limited Medicaments
US5653962A (en) * 1991-12-12 1997-08-05 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicaments
US7498020B2 (en) 1991-12-12 2009-03-03 Glaxo Group Limited Medicaments
US5922306A (en) * 1991-12-12 1999-07-13 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
US5676929A (en) * 1991-12-12 1997-10-14 Glaxo Group Limited Canister containing aerosol formulations containing P134a and particulate medicaments
US20050232873A1 (en) * 1991-12-12 2005-10-20 Glaxo Group Limited Aerosol formulation containing particulate formoterol, propellant and polar cosolvent
US6221339B1 (en) 1991-12-12 2001-04-24 Glaxo Group Limited Medicaments
US6333023B1 (en) 1991-12-12 2001-12-25 Glaxo Group Limited Aerosol formulation containing particulate formoterol, propellant and polar cosolvent
US5658549A (en) * 1991-12-12 1997-08-19 Glaxo Group Limited Aerosol formulations containing propellant 134a and fluticasone propionate
US5674471A (en) * 1991-12-12 1997-10-07 Glaxo Group Limited Aerosol formulations containing P134a and salbutamol
US6200549B1 (en) 1991-12-12 2001-03-13 Glaxo Group Limited Aerosol formulation containing P134a and particulate medicament
US6743413B1 (en) 1991-12-18 2004-06-01 3M Company Suspension aerosol formulations
US7101534B1 (en) 1991-12-18 2006-09-05 3M Innovative Properties Company Suspension aerosol formulations
US7105152B1 (en) 1991-12-18 2006-09-12 3M Innovative Properties Company Suspension aerosol formulations
US20040197273A1 (en) * 1991-12-18 2004-10-07 3M Company Suspension aerosol formulations
WO1994013263A1 (en) * 1992-12-09 1994-06-23 Jager Paul D Stabilized medicinal aerosol solution formulations
AU680227B2 (en) * 1992-12-09 1997-07-24 Boehringer Ingelheim Pharmaceuticals, Inc. Stabilized medicinal aerosol solution formulations
WO1994013262A1 (en) * 1992-12-09 1994-06-23 Boehringer Ingelheim Pharmaceuticals, Inc. Stabilized medicinal aerosol solution formulations
GB2288978A (en) * 1992-12-09 1995-11-08 Boehringer Ingelheim Pharma Stabilized medicinal aerosol solution formulations
GB2288978B (en) * 1992-12-09 1997-04-09 Boehringer Ingelheim Pharma Hydrocarbon inhalant solutions stabilised by organic or inorganic acids
US20050261371A1 (en) * 1993-06-01 2005-11-24 Ono Pharmaceutical Co., Ltd. Pentanoic acid derivatives
US20050267168A1 (en) * 1993-06-01 2005-12-01 Ono Pharmaceutical Co., Ltd. Pentanoic acid derivatives
US20050267167A1 (en) * 1993-06-01 2005-12-01 Ono Pharmaceutical Co., Ltd. Pentanoic acid derivatives
US7176240B2 (en) 1993-06-01 2007-02-13 Ono Pharmaceutical Co., Ltd. Pentanoic acid derivatives
US7569609B2 (en) 1993-06-01 2009-08-04 Ono Pharmaceutical Co., Ltd. Pentanoic acid derivatives
US7569608B2 (en) 1993-06-01 2009-08-04 Ono Pharmaceutical Co., Ltd. Pentanoic acid derivatives
US20030096802A1 (en) * 1993-06-01 2003-05-22 Ono Pharmaceutical Co., Ltd. Pentanoic acid derivatives
US5534536A (en) * 1993-08-24 1996-07-09 Ono Pharmaceuticals Co. Ltd. Fused phenol derivatives
US5750544A (en) * 1993-08-24 1998-05-12 Ono Pharmaceuticals Co., Ltd. Fused phenol derivatives
US5514713A (en) * 1993-12-03 1996-05-07 Ono Pharmaceutical Co., Ltd. Amidinophenol derivatives
US5980867A (en) * 1993-12-20 1999-11-09 3M Innovative Prperties Company Flunisolide aerosol formulations
US5776433A (en) * 1993-12-20 1998-07-07 Minnesota Mining And Manufacturing Company Flunisolide aerosol formulations
EP0703216A1 (en) 1994-09-20 1996-03-27 Ono Pharmaceutical Co., Ltd. Amidinophenol derivatives as protease inhibitors
US5916540A (en) * 1994-10-24 1999-06-29 Glaxo Group Limited Aerosol formulations containing P134A and/or P227 and particulate medicament
US5679287A (en) * 1995-04-28 1997-10-21 Great Lakes Chemical Corporation Uses of heptafluoropropane
WO1996033913A1 (en) * 1995-04-28 1996-10-31 Great Lakes Chemical Corporation Novel uses of heptafluoropropane
US5840213A (en) * 1995-04-28 1998-11-24 Great Lakes Chemical Corporation Uses of heptafluoropropane
EP0757037A2 (en) 1995-07-28 1997-02-05 Ono Pharmaceutical Co., Ltd. Sulfonylamino acid derivatives as metalloproteinase inhibitors
US6022893A (en) * 1995-08-08 2000-02-08 Ono Pharmaceutical Co., Ltd. Hydroxamic acid derivatives
US20070071803A1 (en) * 1996-02-19 2007-03-29 Acrux Dds Pty Ltd Dermal penetration enhancers and drug delivery systems involving same
US20080131494A1 (en) * 1996-02-19 2008-06-05 Acrux Dds Pty Ltd. Dermal Penetration enhancers and drug delivery systems involving same
US5861268A (en) * 1996-05-23 1999-01-19 Biomide Investment Limited Partnership Method for induction of tumor cell apoptosis with chemical inhibitors targeted to 12-lipoxygenase
US6054488A (en) * 1996-06-11 2000-04-25 3M Innovative Properties Company Medicinal aerosol formulations of formoterol
US20090246148A1 (en) * 1996-08-01 2009-10-01 Norton Healthcare Ltd Medicinal aerosols and methods of delivery thereof
US7566445B1 (en) 1996-08-01 2009-07-28 Norton Healthcare Limited Medicinal aerosols and methods of delivery thereof
US8834849B2 (en) 1996-08-01 2014-09-16 Norton Healthcare Limited Medicinal aerosols and methods of delivery thereof
US9650203B2 (en) 1996-08-01 2017-05-16 Norton Healthcare Limited Medicinal aerosols and methods of delivery thereof
AU721920B2 (en) * 1996-08-01 2000-07-20 Norton Healthcare Limited Aerosol formulations
US6461591B1 (en) 1997-02-05 2002-10-08 Jago Research Ag Medical aerosol formulations
US5891419A (en) * 1997-04-21 1999-04-06 Aeropharm Technology Limited Environmentally safe flunisolide aerosol formulations for oral inhalation
US6129905A (en) * 1997-04-21 2000-10-10 Aeropharm Technology, Inc. Aerosol formulations containing a sugar as a dispersant
US5891420A (en) * 1997-04-21 1999-04-06 Aeropharm Technology Limited Environmentally safe triancinolone acetonide aerosol formulations for oral inhalation
US20070021323A1 (en) * 1997-05-27 2007-01-25 Government of the USA, represented by the Secretary, Use of a nitroxide or a prodrug thereof in the prophylactic and therapeutic treatment of cancer
US20040062720A1 (en) * 1997-06-13 2004-04-01 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
EP2253642A1 (en) 1997-12-26 2010-11-24 ONO Pharmaceutical Co., Ltd. Polypeptides, cDNAs encoding the same and utilization thereof
EP2264059A1 (en) 1997-12-26 2010-12-22 ONO Pharmaceutical Co., Ltd. Polypeptides, cDNAs encoding the same and utilization thereof
US6585958B1 (en) 1998-07-24 2003-07-01 Jago Research Ag Medicinal aerosol formulations
US6475467B1 (en) 1998-08-04 2002-11-05 Jago Research Ag Medicinal aerosol formulations
US6458338B1 (en) 1998-09-22 2002-10-01 Aeropharm Technology Incorporated Amino acid stabilized medicinal aerosol formulations
US6136294A (en) * 1998-09-22 2000-10-24 Aeropharm Technology Inc. Amino acid stabilized medical aerosol formulation
US20050142071A1 (en) * 1998-11-25 2005-06-30 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
US20030089369A1 (en) * 1998-11-25 2003-05-15 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
US20040033201A1 (en) * 1999-06-18 2004-02-19 3M Innovative Properties Company Process for making chemically stable C-17/21 OH 20-ketosteroid aerosol products
US20050220717A1 (en) * 1999-06-18 2005-10-06 3M Innovative Properties Company Steroid solution aerosol products with enhanced chemical stability
EP2255829A2 (en) 2001-07-23 2010-12-01 Ono Pharmaceutical Co., Ltd. Pharmaceutical composition for treatment of diseases associated with decrease in bone mass comprising EP4 agonist as active ingredient
EP2281818A1 (en) 2002-02-19 2011-02-09 Ono Pharmaceutical Co., Ltd. Fused pyridazine derivative compounds and drugs containing these compounds as the active ingredient
US10251881B2 (en) 2002-04-17 2019-04-09 Nektar Therapeutics Particulate materials
US8080236B2 (en) 2002-04-17 2011-12-20 Nektar Therapeutics Uk, Ltd Particulate materials
US9616060B2 (en) 2002-04-17 2017-04-11 Nektar Therapeutics Particulate materials
US20030223939A1 (en) * 2002-04-17 2003-12-04 Andreas Kordikowski Particulate materials
US8828359B2 (en) 2002-04-17 2014-09-09 Nektar Therapeutics Particulate materials
US8470301B2 (en) 2002-04-17 2013-06-25 Nektar Therapeutics Particulate materials
US7582284B2 (en) 2002-04-17 2009-09-01 Nektar Therapeutics Particulate materials
US20100166674A1 (en) * 2002-06-25 2010-07-01 Acrux Dds Pty Ltd Transdermal delivery rate control using amorphous pharmaceutical compositions
US8784878B2 (en) 2002-06-25 2014-07-22 Acrux DDS Pty Ltc. Transdermal delivery rate control using amorphous pharmaceutical compositions
US8357393B2 (en) 2002-06-25 2013-01-22 Acrux Dds Pty Ltd. Transdermal delivery rate control using amorphous pharmaceutical compositions
US20050175680A1 (en) * 2002-06-25 2005-08-11 Acrux Dds Pty Ltd. Transdermal delivery rate control using amorphous pharmaceutical compositions
US20050181032A1 (en) * 2002-06-25 2005-08-18 Acrux Dds Pty Ltd. Metastable pharmaceutical compositions
US20050186141A1 (en) * 2002-06-25 2005-08-25 Acrux Dds Pty Ltd. Transdermal aerosol compositions
EP2508204A2 (en) 2002-06-26 2012-10-10 Ono Pharmaceutical Co., Ltd. Remedies for diseases caused by vascular contraction or dilation
EP2243493A1 (en) 2002-07-03 2010-10-27 Ono Pharmaceutical Co., Ltd. Immunopotentiative composition
WO2004031118A1 (en) 2002-10-03 2004-04-15 Ono Pharmaceutical Co., Ltd. Lpa receptor antagonists
EP2565178A1 (en) 2002-10-03 2013-03-06 Ono Pharmaceutical Co., Ltd. LPA Receptor Antagonists
WO2004032965A1 (en) 2002-10-10 2004-04-22 Ono Pharmaceutical Co., Ltd. Endogenous repair factor production promoters
EP2465537A1 (en) 2002-10-10 2012-06-20 ONO Pharmaceutical Co., Ltd. Microspheres comprising ONO-1301
US20060128810A1 (en) * 2002-10-10 2006-06-15 Kyoto University Remedies for allergic diseases
EP2270051A2 (en) 2003-01-23 2011-01-05 Ono Pharmaceutical Co., Ltd. Antibody specific for human PD-1 and CD3
EP2385040A1 (en) 2003-03-14 2011-11-09 ONO Pharmaceutical Co., Ltd. Nitrogen-containing heterocyclic derivatives and drugs containing the same as the active ingredient
EP2364982A1 (en) 2003-04-18 2011-09-14 ONO Pharmaceutical Co., Ltd. Spiro-piperidine compounds as chemokine receptor antagonists and medicinal use thereof
US20050107306A1 (en) * 2003-05-16 2005-05-19 Barr Philip J. Treatment of respiratory disease associated with matrix metalloproteases by inhalation of synthetic matrix metalloprotease inhibitors
US20050069918A1 (en) * 2003-05-29 2005-03-31 Francois Claret JAB1 as a prognostic marker and a therapeutic target for human cancer
US8722340B2 (en) 2003-05-29 2014-05-13 Board Of Regents, The University Of Texas System JAB1 as a prognostic marker and a therapeutic target for human cancer
EP2422814A1 (en) 2003-07-25 2012-02-29 Ono Pharmaceutical Co., Ltd. Remedy for cartilage-related diseases
EP2883865A1 (en) 2003-08-29 2015-06-17 Ono Pharmaceutical Co., Ltd. Compound capable of binding S1P receptor and pharmaceutical use thereof
EP2481732A1 (en) 2003-09-01 2012-08-01 Ono Pharmaceutical Co., Ltd. Condensed ring compound and use thereof
US20070253913A1 (en) * 2003-09-10 2007-11-01 Nahed Mohsen Aerosol formulations for delivery of dihydroergotamine to the systemic circulation via pulmonary inhalation
US20080064674A1 (en) * 2003-10-20 2008-03-13 Schering Corporation Pharmaceutical Compositions
WO2005063704A1 (en) 2003-12-25 2005-07-14 Ono Pharmaceutical Co., Ltd. Azetidine ring compounds and drugs comprising the same
EP2308562A2 (en) 2003-12-25 2011-04-13 Ono Pharmaceutical Co., Ltd. Azetidine ring compounds and drugs comprising the same
US20060018840A1 (en) * 2004-06-28 2006-01-26 Nektar Therapeutics Aerosolizable formulation comprising nicotine
EP2465538A2 (en) 2004-10-21 2012-06-20 Ono Pharmaceutical Co., Ltd. Use of immunesuppressant receptor
EP3115057A1 (en) 2004-10-21 2017-01-11 ONO Pharmaceutical Co., Ltd. Use of immunesuppressant receptor
US20060110328A1 (en) * 2004-11-24 2006-05-25 Cagle Gerald D Method of delivering nasal spray
AU2005309951B2 (en) * 2004-11-24 2011-07-07 Alcon, Inc. Method of delivering nasal spray
US9522143B2 (en) 2005-02-02 2016-12-20 Mitos Pharmaceuticals, Inc. Nitroxides for use in treating or preventing diabetes and obesity
US10245256B2 (en) 2005-02-02 2019-04-02 Mitos Pharmaceuticals, Inc. Nitroxides for use in treating or preventing diabetes and obesity
US9522144B2 (en) 2005-02-02 2016-12-20 Mitos Pharmaceuticals, Inc. Nitroxides for use in treating or preventing diabetes and obesity
US10987357B2 (en) 2005-05-18 2021-04-27 Horizon Orphan, LLC Aerosolized fluoroquinolones and uses thereof
US20100166673A1 (en) * 2005-05-18 2010-07-01 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8357696B2 (en) 2005-05-18 2013-01-22 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8546423B2 (en) 2005-05-18 2013-10-01 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US20100158957A1 (en) * 2005-05-18 2010-06-24 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8524735B2 (en) 2005-05-18 2013-09-03 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8524734B2 (en) 2005-05-18 2013-09-03 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
EP2594272A2 (en) 2005-05-18 2013-05-22 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US20100037890A1 (en) * 2005-05-18 2010-02-18 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US20100040560A1 (en) * 2005-05-18 2010-02-18 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US20120316246A1 (en) * 2005-06-17 2012-12-13 Fahl William E Topical vasoconstrictor preparations and methods for protecting cells during cancer chemotherapy and radiotherapy
US11197836B2 (en) 2005-06-17 2021-12-14 Wisconsin Alumni Research Foundation Topical vasoconstrictor preparations and methods for protecting cells during cancer chemotherapy and radiotherapy
WO2007049771A1 (en) 2005-10-28 2007-05-03 Ono Pharmaceutical Co., Ltd. Compound containing basic group and use thereof
EP2657235A1 (en) 2005-10-28 2013-10-30 Ono Pharmaceutical Co., Ltd. Compound containing basic group and use thereof
WO2007069565A1 (en) 2005-12-12 2007-06-21 Ono Pharmaceutical Co., Ltd. Bicyclic heterocyclic compound
WO2007069671A1 (en) 2005-12-15 2007-06-21 Ono Pharmaceutical Co., Ltd. Bicyclic heterocyclic compound
US20090191134A1 (en) * 2006-06-12 2009-07-30 Medispray Laboratoriespvt. Ltd. Stable aerosol pharmaceutical formulations
US20100284940A1 (en) * 2007-02-11 2010-11-11 Map Pharmaceuticals, Inc. Method of therapeutic administration of dhe to enable rapid relief of migraine while minimizing side effect profile
US7994197B2 (en) 2007-02-11 2011-08-09 Map Pharmaceuticals, Inc. Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile
US8148377B2 (en) 2007-02-11 2012-04-03 Map Pharmaceuticals, Inc. Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile
US8119639B2 (en) 2007-02-11 2012-02-21 Map Pharmaceuticals, Inc. Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile
US20100081663A1 (en) * 2007-02-11 2010-04-01 Map Pharmaceuticals, Inc. Method of therapeutic administration of dhe to enable rapid relief of migraine while minimizing side effect profile
US20080287451A1 (en) * 2007-02-11 2008-11-20 Cook Robert O Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile
US20100081664A1 (en) * 2007-02-11 2010-04-01 Map Pharmaceuticals, Inc. Method of therapeutic administration of dhe to enable rapid relief of migraine while minimizing side effect profile
US9833451B2 (en) 2007-02-11 2017-12-05 Map Pharmaceuticals, Inc. Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile
US10172853B2 (en) 2007-02-11 2019-01-08 Map Pharmaceuticals, Inc. Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile
WO2008136377A1 (en) 2007-04-26 2008-11-13 Ono Pharmaceutical Co., Ltd. Bicyclic heterocyclic compound
DE102008007198A1 (en) 2008-02-01 2009-08-13 Infectopharm Arzneimittel Und Consilium Gmbh Oral or nasally administrable formulations containing epinephrine with improved properties
EP2085071A1 (en) 2008-02-01 2009-08-05 Infectopharm Arzneimittel und Consilium GmbH Orally or nasally administrable preparations containing epinephrine with improved characteristics
US9717738B2 (en) 2008-10-07 2017-08-01 Horizon Orphan Llc Aerosol fluoroquinolone formulations for improved pharmacokinetics
US10722519B2 (en) 2008-10-07 2020-07-28 Horizon Orphan Llc Aerosol fluoroquinolone formulations for improved pharmacokinetics
US20100087416A1 (en) * 2008-10-07 2010-04-08 Mpex Pharmaceuticals, Inc. Aerosol fluoroquinolone formulations for improved pharmacokinetics
US8815838B2 (en) 2008-10-07 2014-08-26 David C. Griffith Aerosol fluoroquinolone formulations for improved pharmacokinetics
US11020481B2 (en) 2008-10-07 2021-06-01 Horizon Orphan Llc Topical use of levofloxacin for reducing lung inflammation
US9326936B2 (en) 2008-10-07 2016-05-03 Raptor Pharmaceuticals, Inc. Aerosol fluoroquinolone formulations for improved pharmacokinetics
US20100087386A1 (en) * 2008-10-07 2010-04-08 Mpex Pharmaceuticals, Inc. Topical use of levofloxacin for reducing lung inflammation
US10149854B2 (en) 2008-10-07 2018-12-11 Horizon Orphan Llc Aerosol fluoroquinolone formulations for improved pharmacokinetics
US8629139B2 (en) 2008-10-07 2014-01-14 Mpex Pharmaceuticals, Inc. Topical use of Levofloxacin for reducing lung inflammation
EP2206698A1 (en) 2008-12-22 2010-07-14 ONO Pharmaceutical Co., Ltd. Ethynylindole compounds
WO2010147133A1 (en) 2009-06-17 2010-12-23 小野薬品工業株式会社 Novel imidazopyridine compound
US20110171141A1 (en) * 2009-06-26 2011-07-14 Kellerman Donald J Administration of dihydroergotamine mesylate particles using a metered dose inhaler
US9700564B2 (en) 2009-09-04 2017-07-11 Horizon Orphan Llc Use of aerosolized levofloxacin for treating cystic fibrosis
US10231975B2 (en) 2009-09-04 2019-03-19 Horizon Orphan Llc Use of aerosolized levofloxacin for treating cystic fibrosis
US10792289B2 (en) 2009-09-04 2020-10-06 Horizon Orphan Llc Use of aerosolized levofloxacin for treating cystic fibrosis
WO2011066537A1 (en) 2009-11-30 2011-06-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Nitroxide therapy for the treatment of von hippel - lindau disease (vhl) and renal clear cell carcinoma (rcc)
US8853277B2 (en) 2009-11-30 2014-10-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Nitroxide therapy for the treatment of von Hippel—Lindau disease (VHL) and renal clear cell carcinoma (RCC)
WO2011162222A1 (en) 2010-06-21 2011-12-29 小野薬品工業株式会社 Novel crystalline forms of 4,4'-[4-fluoro-7-({4-[4-(3-fluoro-2-methylphenyl)butoxy]phenyl}ethynyl)-2-methyl-1h-indole-1,3-diyl]dibutanoic acid, 4,4'-[2-methyl-7-({4-[4-(pentafluorophenyl)butoxy]phenyl}ethynyl)-1h-indole-1,3-diyl]dibutanoic acid, and 4,4'-[4-fluoro-2-methyl-7-({4-[4-(2,3,4,6-tetrafluorophenyl)butoxy]phenyl}ethynyl)-1h-indole-1,3-diyl]dibutanoic acid
WO2012074069A1 (en) 2010-12-02 2012-06-07 小野薬品工業株式会社 Novel compound and medical use thereof
WO2012106382A1 (en) 2011-01-31 2012-08-09 Genoa Pharmaceuticals, Inc. Aerosol pirfenidone and pyridone analog compounds and uses thereof
EP4059499A1 (en) 2011-01-31 2022-09-21 Avalyn Pharma Inc. Aerosol pirfenidone and pyridone analog compounds and uses thereof
WO2012127885A1 (en) 2011-03-18 2012-09-27 小野薬品工業株式会社 Tetrahydrocarboline derivative
WO2013161919A1 (en) 2012-04-26 2013-10-31 小野薬品工業株式会社 Trk-INHIBITING COMPOUND
EP3459935A1 (en) 2013-02-19 2019-03-27 ONO Pharmaceutical Co., Ltd. Trk-inhibiting compound
EP3800183A1 (en) 2013-02-19 2021-04-07 ONO Pharmaceutical Co., Ltd. Urea derivatives as trk-inhibiting compounds
WO2014129431A1 (en) 2013-02-19 2014-08-28 小野薬品工業株式会社 Trk-INHIBITING COMPOUND
EP3782604A1 (en) 2013-07-31 2021-02-24 Windward Pharma, Inc. Aerosol tyrosine kinase inhibitor compounds and uses thereof
US10028966B2 (en) 2014-01-10 2018-07-24 Avalyn Pharma Inc. Aerosol pirfenidone and pyridone analog compounds and uses thereof
WO2015115673A1 (en) 2014-01-31 2015-08-06 Ono Pharmaceutical Co., Ltd. Fused imidazole compounds
WO2018101309A1 (en) 2016-11-30 2018-06-07 大日本住友製薬株式会社 Wt1 helper peptide, and combination of said peptide and cancer antigen peptide conjugate
WO2018181648A1 (en) 2017-03-30 2018-10-04 大日本住友製薬株式会社 Wt1 cancer antigen peptide and peptide conjugate body containing same
WO2019049891A1 (en) 2017-09-06 2019-03-14 小野薬品工業株式会社 METHOD FOR TREATING CANCER BY COMBINATION OF Trk INHIBITOR AND KINASE INHIBITOR
WO2019230919A1 (en) 2018-05-31 2019-12-05 小野薬品工業株式会社 Biomarker for judging efficacy of immune checkpoint inhibitor
WO2020075790A1 (en) 2018-10-11 2020-04-16 小野薬品工業株式会社 Sting-agonist compound
WO2021025031A1 (en) 2019-08-05 2021-02-11 小野薬品工業株式会社 Biomarker for accessing efficacy of immune checkpoint inhibitor
WO2021107125A1 (en) 2019-11-29 2021-06-03 小野薬品工業株式会社 Compound having lysophosphatidic acid receptor agonistic activity and pharmaceutical use of said compound
EP4066895A1 (en) 2019-11-29 2022-10-05 ONO Pharmaceutical Co., Ltd. Compound having lysophosphatidic acid receptor agonistic activity and pharmaceutical use of said compound
WO2021205631A1 (en) 2020-04-10 2021-10-14 小野薬品工業株式会社 Sting agonistic compound
WO2021230247A1 (en) 2020-05-12 2021-11-18 大日本住友製薬株式会社 Pharmaceutical composition for treating cancer
WO2022240897A1 (en) 2021-05-10 2022-11-17 Sepelo Therapeutics, Llc Pharmaceutical composition comprising delafloxacin for administration into the lung
WO2022251679A1 (en) 2021-05-27 2022-12-01 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Nitroxide radicals for use as antiviral treatment for coronavirus infection
WO2023028364A1 (en) 2021-08-27 2023-03-02 Sepelo Therapeutics, Llc Targeted compositions and uses therof

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