CA1136547A - Aerosol anesthetic compositions - Google Patents
Aerosol anesthetic compositionsInfo
- Publication number
- CA1136547A CA1136547A CA000345059A CA345059A CA1136547A CA 1136547 A CA1136547 A CA 1136547A CA 000345059 A CA000345059 A CA 000345059A CA 345059 A CA345059 A CA 345059A CA 1136547 A CA1136547 A CA 1136547A
- Authority
- CA
- Canada
- Prior art keywords
- composition
- propellant
- benzocaine
- solvent
- polyethylene glycol
- 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.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE - Novel liquid anesthetic aerosol compositions compri-sing high concentrations of benzocaine in a water washable base with propellants which are resistant to cold temperatures are disclosed.
Description
AHP-7000 - cl 113~7 AEROSOL ANESTHETIC COMPOSITIONS
BACKGROUND OF THE INVENTION
1. Field of the Invention:
;This invention relates to liquid compositions of anesthetic agents in aerosol con-tainers. More specifically, this invention relates to liquid compositions of the anesthetic -I benzocaine which form single phase mixtures in combination with solvent and ~ hydrocarbon propellants, and which remain single phase at low temperatures and high i concentrations of benzocaine.
,
BACKGROUND OF THE INVENTION
1. Field of the Invention:
;This invention relates to liquid compositions of anesthetic agents in aerosol con-tainers. More specifically, this invention relates to liquid compositions of the anesthetic -I benzocaine which form single phase mixtures in combination with solvent and ~ hydrocarbon propellants, and which remain single phase at low temperatures and high i concentrations of benzocaine.
,
2. Description of the Prior Art:
Benzocaine, the ethyl ester, ester of p-aminobenzoic acid, is a well known local anesthetic which has been topically administered in the form of ointments, lotions, sprays, gels and as an impregnant in first aid pads. In order to enhance or prolong benzo-eaine's anesthetic activity, various efforts have been made to increase the concentration of benzocaine in various solvents or to more effectively maintain the anesthetic at its site of administration. Increasing the concentration of benzocaine, however, had to be balanced against the increasing probability of benzocaine precipitation, particularly at colder temperatures, thereby limiting their field of use. The goal of formulating highly concentrated benzocaine compositions characterized by cold temperature resistance is even greater in aerosol anesthetic compositions wherein even small amounts of precipitate can clog valves and orifices, and wherein sufficient pressure must be maintained to both completely deliver all the benzocaine solution within the container and evenly distribute the benzocaine solution with desirable spray characteristics.
Many solvents have been disclosed for benzocaine. For example, U. S. Patent 2,187,597 discloses anesthetic formulations containing up to five percent of the anesthetic agent in a mixture of benzyl alcohol and ethyl chloride. Other formulations q~
Benzocaine, the ethyl ester, ester of p-aminobenzoic acid, is a well known local anesthetic which has been topically administered in the form of ointments, lotions, sprays, gels and as an impregnant in first aid pads. In order to enhance or prolong benzo-eaine's anesthetic activity, various efforts have been made to increase the concentration of benzocaine in various solvents or to more effectively maintain the anesthetic at its site of administration. Increasing the concentration of benzocaine, however, had to be balanced against the increasing probability of benzocaine precipitation, particularly at colder temperatures, thereby limiting their field of use. The goal of formulating highly concentrated benzocaine compositions characterized by cold temperature resistance is even greater in aerosol anesthetic compositions wherein even small amounts of precipitate can clog valves and orifices, and wherein sufficient pressure must be maintained to both completely deliver all the benzocaine solution within the container and evenly distribute the benzocaine solution with desirable spray characteristics.
Many solvents have been disclosed for benzocaine. For example, U. S. Patent 2,187,597 discloses anesthetic formulations containing up to five percent of the anesthetic agent in a mixture of benzyl alcohol and ethyl chloride. Other formulations q~
3~S47 containing up to 10% benzocaine in mixtures with a procaine salt, water, water miscible poly-hydroxy aliphathic alcohols and their ethers have been disclosed in U. S. Patent 2,382,546. U. S. Patent 2,457,188 discloses benzocaine solutions containing at least 10%
benzocaine at 20 C utilizing solvents selected from certain polyoxyalkylene glycols, aliphatic ethers of dihydric alcohols, aromatic ethers of aliphatic dihydric alcohols, carboxylic acid esters of aliphatic dihydric alcohols, and carboxylic acid esters of aromatic and aliphatic ethers of aliphatic dihydric alcohols. In U. S. Patent 2,682,182, benzocaine solutions containing up to 16% benzocaine at 0 C were disclosed in a mixture employing a major amount of propylene glycol and a polyoxyethylene (8-25) hexitan monolaurate.
Anesthetic aerosol preparations containing at least 1~% benzocaine in diesters of i 11 C8-C12 carboxylic acids and polyethylene glycols having a molecular weight of approximately 300 - 600, and a propellant system made *om mixture of chlorofluoro-hydrocarbons have been disclosed in U. S. Patent 3,322,634. These aerosol formulations, however, are no longer acceptable because of certain atmospheric effects associated with chlorofluorohydrocarbons.
Benzocaine has also been employed in formulations containing certain other therapeutic ingredients, for example, as disclosed in U. S. Patent 3,808,319 wherein the solvent is volatile alcohol such as ethyl alcohol or isopropyl alcohol. Solvents of this type, however, are generally counterproductive to desirable anesthetic properties because of their stinging nature to sensitive or wounded skin and the like. Compositions containing up to 15% benzocaine are further disclosed in U. S. Patent 4,052,513 in the form of oil in water emulsions.
.
~ SUMMARY OF THE INVENTION
' This invention provides liquid anesthetic compositions in aerosol containers. The - composition of this invention comprises a single phase mixture of a water washable base of the preferred anesthetic benzocaine in a solvent and a hydrocarbon propellant.
., ~A 2 ~ 1~3~5~7 The weight percent of the benzocaine in the solvent is from about 0.5% up to its maximum solubility in the solvent. Selection of the solvent is made from at least one of polyoxyethylene sorbitan trioleate which has an average of about 20 units of ethylene oxide in the polyoxyethylene chain, polyethylene glycol monolaurate wherein the polyethylene glycol has an average molecular weight of about 200 to about 600 and polyethylene glycol dilaurate wherein the polyethylene glycol has an average molecular weight of about 400. The hydrocarbon propellant of the compositions of this invention is selected from difluoroethane and at least one of n-butane, iso-butane and n-propane.
This invention is further defined by the provision that the composition is a single phase mixture after exposure to temperatures of about -20 C when the benzocaine comprises about 20% by weight of the water washable base of benzocaine and solvent.
While the invention is illustrated with the anesthetic benzocaine, it will be apparent to those skilled in the art that the composition of this invention is also suitable for other therapeutic agents deliverable from aerosol containers in which water washability, single phase cold temperature resistance and nonstinging of solvents are desirable characteristics.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to liquid anesthetic compositions in aerosol containers comprising a single phase mixture of a water washable base of benzocaine in a solvent and a hydrocarbon propellant. The weight percent of benzocaine in the water washable base is from about 0.5% up to its maximum solubility in the solvent. For most effective anesthetic properties, the benzocaine comprises at least 10% by weight of the base and preferred compositions conWn about 20% by weight of benzocaine.
Solvents useful in this invention are selected from at least one of polyoxyethylene sorbitan trioleate having an average of about 20 units of ethylene oxide in the polyoxy-ethylene chain, polyethylene glycol monolaurate and polyethylene glycol dilaurate 1~3~547 wherein the polyethylene glycol has an average molecular weight of about 400. Although wider ranges of one solvent to another are acceptable, the solvent is preferably selected from two of the herein listed class of solvents in a ratio of 40:60 to each other, and most desirably in a ratio of 50:50.
The propellant system comprises difluoroethane and at least one of n-butane, isobutane and n-propane. In the preferred system which utilîzes n-butane, the difluoro-ethane comprises about 35 - 70% by weight of the propellant system. In the most preferred embodiments each of the propellants in a two propellant system comprise about 50% of the total propellant.
Further, the water washable base of benzocaine in solvent and the propellant each comprise about 45% to about 55% by weight of the liquid anesthetic composition, and in preferred embodiments, about 50%.
, I
The compositions of this invention are further defined by the provision that thecompositions form a single phase, clear liquid solution following exposure to tempera-tures of -20C, when the benzocaine comprises about 20% of said water washable base, I and in preferred embodiments, the composition is a single phase mixture at about -20 C.
A ,I Compositions having the preferred single phase characteristics at -20C employ poly-~ ethyleneglycol monolaurate, or mixtures of polyoxyethylene sorbitan trioleate with the g polyethyleneglycol mono- or di- laurate as the solventO
.. ..
In formulating the compositon of this invention, other ingredients, such as anti-pruritic agents, anti-infectives, anti-fungal agents and anti-bacterial agents are typically incorporated.
'' ;' r `' ;;
~ .~
113~S47 i The following composition is an illustration of a preferred embodiment of this invention:
Water Washable Base ¦ Benzocaine 200.0 g Menthol 5.0 g i Methylparaben 10.0 g Polyoxyethylene 20 Sorbitan Trioleate 392.5 g Il Polyethyleneglycol 400 Monolaurate 392.5 g 'I i I I
The composition of the invention may be prepared by charging the solvent into a suitable container equipped with a stirrer, adding the benzocaine and/or other active ingredients and mixing until dissolution. The solution is then filtered through a suitable l screen and loaded into an aerosol container along with the propellants in R conventional i~ manner.
., A suitable container for the composition of this invention is a can having a "2P"
rating as specified by the United States Department of Transportation. Among the valve systems which have been employed satisfactorily in any position are those similar to a Seaquist NS-36 or NS-34 (Seaquist Valve Co., Cary, Ill.) or those similar to ARC-KN-37 ., (Ethyl Products Co., North Riverside, Ill.).
The invention is further illustrated by the following examples:
, I
~;, , .
; ; The following bulk concentrates were prepared for further evaluation, , .
_5~
. AHP-7000 1~3~547 BULK CO2~CENTRATES
, I i I II III
il Benzocaine 20 % 20 % 20 %
Menthol 0.5 % 0.5 % 0-5 %
Methylparaben1.0 % 1.0 % 1 .0 %
Polyoxyethylene 20 Sorbitan Trioleate 78.5 %
PEG 400 Monolaurate - 78.5 %
PEG 400 Dilaurllte - - 78.5 %
113~iS47 ~HP-70~0 il Example Bulk Concentrates Propellants Pressure Phvsical Stability # _ I 11 111 d fluoroethane n-butane psi~ ~ 70 F RT -20 C (for I dav) 1. 25% 25% - 25% 25% 57 OK ~ OK
2. 22.5% 22.5% - 27.5% 27.5% 71~ OK OK
3. 27.5% 27.5% - 22.5% 22.5% 71~1' OK OK
1 4. 25% 25% 25% 25% 57 OK OK
; 5. 22.596 - 22.5% 27.5% 27.5% - OK OK
6. 27.5% - 27.5% 22.5% 22.5% - OK OK
~¦ 7. - 25% 25% 25% 25% 45 OK Wt. ppt.
1, wt. ppt (a RT
I 8. - 22.5% 22.5% 27.5% 27.5% - OK Wt. ppt.
i wt. ppt. @ RT
9. - 27.5% 27.5% 22.5% 22.5% - OK Wt. ppt.
: v~, pp~. @ p ;' ~' .~ ~
, ' i ,i Example Bulk Concentrates Propellants Pressure Phvsical Stability 11 111 dilluoroethane n-butane psi~ @ 70 F RT -20 C for I day) ~ - 50% - 350~ 15% - OK OK
Il. _ 50% 30% 20% 57 OK ;)K @ RT
12. - 50% - 25~ 25% 56 OK Wt. ppt 13. - 50% - 20% 3û% 51 OK Wt. ppt ¦¦ 14. _ 50% 35% 15% - OK OK @ RT
15. 50% 30% 20% - OK Wt. ppt.
16. - - 50% 25% 25% OK Wt. ppt.
17. - - 50% 20% 30% - OK \vt. ppt.
wt. ppt @ RT
l 18. - - 50% 15% 35% 43 OK wt ppt @ RT
1 - 19. - - 50% 10% 40% 39 OK Wt. ppt.
wt. ppt. @ RT
20. - - 50% 5% 45% 31 OK Wt. ppt.
l wt. ppt. @ RT
¦ ¦ 21. 25% 25% - 35% ; 15% 63 OK OK
Il 22. 10% 40% - 30% 20% 60 OK OK
j 1 23. 25% 25% - 30% 20% 58 OK OK
24. 25% 25% - 25% 25% 57 OK OK
25. 25% 25% 20% 30% 52 OK OK
26. 25% 25% - 15% 35% - Separation 27. 25% 25% - 18% 32% - OK OK
28. 25% _ 25% 35% 15% - OK Ppt.
29. 10% - 40% 30% 20% - OK Ppt.
30. Z5% - 25% 30% 20% 60 OK OK
I
,, ~13~4~7 AHP-7000 .
ij Exalnple Bulk Concentrates Propellants Pressure Phvsical Stability ~ I 11 lll difluo hane n-butane ~ ~ 70 F RT -20 C (for I dav) 31. 25% - 25C6 25% 25% 57 OK OK
32. 25~ - 25% 20% 30q6 50 OK Wt. ppt.
i OK @ RT
33. - 25% 25% 35% 15% - OK Wt. ppt.
I! OK @ RT
¦~ 34. - 25% 25% 30% 20% - OK Wt. ppt.
¦ OK (3 RT
l 35. - 25% 25% 256 25% 45 OK Wt. ppt.
i wt. ppt. @ RT
36. - 25~ 25~ 20% 30% 50 OK Wt. ppt.
OK @ RT
, 37. - 25% 25~ 15% 35% 45 OK Wt. ppt.
wt. ppt. @ RT
,1 ~ ~ 9 , I
~' 1.13654q AHP-7000 .~
r-~xa nple ~ulk Concentrates ProDellants Pressure Ph~sical Stabililv Ij~7 __ 11 111 dif oethane n-butane psi~ ~. 70 F RT -20 C (f~r I dav) I l 38.25?5 25% _ 25~ 25~6 57 OK OK
¦139. 20~6 30% - 25% 25% 79~ OK OK
40. 30620% - 25% 25% 78~ OK OK
41. 25% - 25% 2596 25% 57 OK Ol;
42. 20~6 - 30% 25% 25% - OK PDt.
ppt. @ RT
l 43. 356 - 20% 25% 25% - OK Ppt.
i ppt. @ RT
l 44. - 25% 25% 25~i 25% 45 OK Wt. ppt.
i wt. ppt. @ RT
1 45. - 20~6 30% 25% 25% - OK Ppt.
i ppt. @ RT
46. - 30% 20% 25% 25% - OK Ppt.
ppt. (~ RT
One phase sys~em, clear solu~ion ' leasured at RT
i
benzocaine at 20 C utilizing solvents selected from certain polyoxyalkylene glycols, aliphatic ethers of dihydric alcohols, aromatic ethers of aliphatic dihydric alcohols, carboxylic acid esters of aliphatic dihydric alcohols, and carboxylic acid esters of aromatic and aliphatic ethers of aliphatic dihydric alcohols. In U. S. Patent 2,682,182, benzocaine solutions containing up to 16% benzocaine at 0 C were disclosed in a mixture employing a major amount of propylene glycol and a polyoxyethylene (8-25) hexitan monolaurate.
Anesthetic aerosol preparations containing at least 1~% benzocaine in diesters of i 11 C8-C12 carboxylic acids and polyethylene glycols having a molecular weight of approximately 300 - 600, and a propellant system made *om mixture of chlorofluoro-hydrocarbons have been disclosed in U. S. Patent 3,322,634. These aerosol formulations, however, are no longer acceptable because of certain atmospheric effects associated with chlorofluorohydrocarbons.
Benzocaine has also been employed in formulations containing certain other therapeutic ingredients, for example, as disclosed in U. S. Patent 3,808,319 wherein the solvent is volatile alcohol such as ethyl alcohol or isopropyl alcohol. Solvents of this type, however, are generally counterproductive to desirable anesthetic properties because of their stinging nature to sensitive or wounded skin and the like. Compositions containing up to 15% benzocaine are further disclosed in U. S. Patent 4,052,513 in the form of oil in water emulsions.
.
~ SUMMARY OF THE INVENTION
' This invention provides liquid anesthetic compositions in aerosol containers. The - composition of this invention comprises a single phase mixture of a water washable base of the preferred anesthetic benzocaine in a solvent and a hydrocarbon propellant.
., ~A 2 ~ 1~3~5~7 The weight percent of the benzocaine in the solvent is from about 0.5% up to its maximum solubility in the solvent. Selection of the solvent is made from at least one of polyoxyethylene sorbitan trioleate which has an average of about 20 units of ethylene oxide in the polyoxyethylene chain, polyethylene glycol monolaurate wherein the polyethylene glycol has an average molecular weight of about 200 to about 600 and polyethylene glycol dilaurate wherein the polyethylene glycol has an average molecular weight of about 400. The hydrocarbon propellant of the compositions of this invention is selected from difluoroethane and at least one of n-butane, iso-butane and n-propane.
This invention is further defined by the provision that the composition is a single phase mixture after exposure to temperatures of about -20 C when the benzocaine comprises about 20% by weight of the water washable base of benzocaine and solvent.
While the invention is illustrated with the anesthetic benzocaine, it will be apparent to those skilled in the art that the composition of this invention is also suitable for other therapeutic agents deliverable from aerosol containers in which water washability, single phase cold temperature resistance and nonstinging of solvents are desirable characteristics.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to liquid anesthetic compositions in aerosol containers comprising a single phase mixture of a water washable base of benzocaine in a solvent and a hydrocarbon propellant. The weight percent of benzocaine in the water washable base is from about 0.5% up to its maximum solubility in the solvent. For most effective anesthetic properties, the benzocaine comprises at least 10% by weight of the base and preferred compositions conWn about 20% by weight of benzocaine.
Solvents useful in this invention are selected from at least one of polyoxyethylene sorbitan trioleate having an average of about 20 units of ethylene oxide in the polyoxy-ethylene chain, polyethylene glycol monolaurate and polyethylene glycol dilaurate 1~3~547 wherein the polyethylene glycol has an average molecular weight of about 400. Although wider ranges of one solvent to another are acceptable, the solvent is preferably selected from two of the herein listed class of solvents in a ratio of 40:60 to each other, and most desirably in a ratio of 50:50.
The propellant system comprises difluoroethane and at least one of n-butane, isobutane and n-propane. In the preferred system which utilîzes n-butane, the difluoro-ethane comprises about 35 - 70% by weight of the propellant system. In the most preferred embodiments each of the propellants in a two propellant system comprise about 50% of the total propellant.
Further, the water washable base of benzocaine in solvent and the propellant each comprise about 45% to about 55% by weight of the liquid anesthetic composition, and in preferred embodiments, about 50%.
, I
The compositions of this invention are further defined by the provision that thecompositions form a single phase, clear liquid solution following exposure to tempera-tures of -20C, when the benzocaine comprises about 20% of said water washable base, I and in preferred embodiments, the composition is a single phase mixture at about -20 C.
A ,I Compositions having the preferred single phase characteristics at -20C employ poly-~ ethyleneglycol monolaurate, or mixtures of polyoxyethylene sorbitan trioleate with the g polyethyleneglycol mono- or di- laurate as the solventO
.. ..
In formulating the compositon of this invention, other ingredients, such as anti-pruritic agents, anti-infectives, anti-fungal agents and anti-bacterial agents are typically incorporated.
'' ;' r `' ;;
~ .~
113~S47 i The following composition is an illustration of a preferred embodiment of this invention:
Water Washable Base ¦ Benzocaine 200.0 g Menthol 5.0 g i Methylparaben 10.0 g Polyoxyethylene 20 Sorbitan Trioleate 392.5 g Il Polyethyleneglycol 400 Monolaurate 392.5 g 'I i I I
The composition of the invention may be prepared by charging the solvent into a suitable container equipped with a stirrer, adding the benzocaine and/or other active ingredients and mixing until dissolution. The solution is then filtered through a suitable l screen and loaded into an aerosol container along with the propellants in R conventional i~ manner.
., A suitable container for the composition of this invention is a can having a "2P"
rating as specified by the United States Department of Transportation. Among the valve systems which have been employed satisfactorily in any position are those similar to a Seaquist NS-36 or NS-34 (Seaquist Valve Co., Cary, Ill.) or those similar to ARC-KN-37 ., (Ethyl Products Co., North Riverside, Ill.).
The invention is further illustrated by the following examples:
, I
~;, , .
; ; The following bulk concentrates were prepared for further evaluation, , .
_5~
. AHP-7000 1~3~547 BULK CO2~CENTRATES
, I i I II III
il Benzocaine 20 % 20 % 20 %
Menthol 0.5 % 0.5 % 0-5 %
Methylparaben1.0 % 1.0 % 1 .0 %
Polyoxyethylene 20 Sorbitan Trioleate 78.5 %
PEG 400 Monolaurate - 78.5 %
PEG 400 Dilaurllte - - 78.5 %
113~iS47 ~HP-70~0 il Example Bulk Concentrates Propellants Pressure Phvsical Stability # _ I 11 111 d fluoroethane n-butane psi~ ~ 70 F RT -20 C (for I dav) 1. 25% 25% - 25% 25% 57 OK ~ OK
2. 22.5% 22.5% - 27.5% 27.5% 71~ OK OK
3. 27.5% 27.5% - 22.5% 22.5% 71~1' OK OK
1 4. 25% 25% 25% 25% 57 OK OK
; 5. 22.596 - 22.5% 27.5% 27.5% - OK OK
6. 27.5% - 27.5% 22.5% 22.5% - OK OK
~¦ 7. - 25% 25% 25% 25% 45 OK Wt. ppt.
1, wt. ppt (a RT
I 8. - 22.5% 22.5% 27.5% 27.5% - OK Wt. ppt.
i wt. ppt. @ RT
9. - 27.5% 27.5% 22.5% 22.5% - OK Wt. ppt.
: v~, pp~. @ p ;' ~' .~ ~
, ' i ,i Example Bulk Concentrates Propellants Pressure Phvsical Stability 11 111 dilluoroethane n-butane psi~ @ 70 F RT -20 C for I day) ~ - 50% - 350~ 15% - OK OK
Il. _ 50% 30% 20% 57 OK ;)K @ RT
12. - 50% - 25~ 25% 56 OK Wt. ppt 13. - 50% - 20% 3û% 51 OK Wt. ppt ¦¦ 14. _ 50% 35% 15% - OK OK @ RT
15. 50% 30% 20% - OK Wt. ppt.
16. - - 50% 25% 25% OK Wt. ppt.
17. - - 50% 20% 30% - OK \vt. ppt.
wt. ppt @ RT
l 18. - - 50% 15% 35% 43 OK wt ppt @ RT
1 - 19. - - 50% 10% 40% 39 OK Wt. ppt.
wt. ppt. @ RT
20. - - 50% 5% 45% 31 OK Wt. ppt.
l wt. ppt. @ RT
¦ ¦ 21. 25% 25% - 35% ; 15% 63 OK OK
Il 22. 10% 40% - 30% 20% 60 OK OK
j 1 23. 25% 25% - 30% 20% 58 OK OK
24. 25% 25% - 25% 25% 57 OK OK
25. 25% 25% 20% 30% 52 OK OK
26. 25% 25% - 15% 35% - Separation 27. 25% 25% - 18% 32% - OK OK
28. 25% _ 25% 35% 15% - OK Ppt.
29. 10% - 40% 30% 20% - OK Ppt.
30. Z5% - 25% 30% 20% 60 OK OK
I
,, ~13~4~7 AHP-7000 .
ij Exalnple Bulk Concentrates Propellants Pressure Phvsical Stability ~ I 11 lll difluo hane n-butane ~ ~ 70 F RT -20 C (for I dav) 31. 25% - 25C6 25% 25% 57 OK OK
32. 25~ - 25% 20% 30q6 50 OK Wt. ppt.
i OK @ RT
33. - 25% 25% 35% 15% - OK Wt. ppt.
I! OK @ RT
¦~ 34. - 25% 25% 30% 20% - OK Wt. ppt.
¦ OK (3 RT
l 35. - 25% 25% 256 25% 45 OK Wt. ppt.
i wt. ppt. @ RT
36. - 25~ 25~ 20% 30% 50 OK Wt. ppt.
OK @ RT
, 37. - 25% 25~ 15% 35% 45 OK Wt. ppt.
wt. ppt. @ RT
,1 ~ ~ 9 , I
~' 1.13654q AHP-7000 .~
r-~xa nple ~ulk Concentrates ProDellants Pressure Ph~sical Stabililv Ij~7 __ 11 111 dif oethane n-butane psi~ ~. 70 F RT -20 C (f~r I dav) I l 38.25?5 25% _ 25~ 25~6 57 OK OK
¦139. 20~6 30% - 25% 25% 79~ OK OK
40. 30620% - 25% 25% 78~ OK OK
41. 25% - 25% 2596 25% 57 OK Ol;
42. 20~6 - 30% 25% 25% - OK PDt.
ppt. @ RT
l 43. 356 - 20% 25% 25% - OK Ppt.
i ppt. @ RT
l 44. - 25% 25% 25~i 25% 45 OK Wt. ppt.
i wt. ppt. @ RT
1 45. - 20~6 30% 25% 25% - OK Ppt.
i ppt. @ RT
46. - 30% 20% 25% 25% - OK Ppt.
ppt. (~ RT
One phase sys~em, clear solu~ion ' leasured at RT
i
Claims (12)
1. A liquid anesthetic composition in an aerosol container comprising a single phase mixture of a water washable base of benzocaine in a solvent and a hydrocarbon propellant wherein, (a) the weight percent of said benzocaine in the solvent is from 0.5% up to its maximum solubility in the solvent;
(b) the solvent is selected from at least one of polyoxyethylene sorbitan trioleate having an average of about 20 units of ethylene oxide in the polyoxyethylene chain, polyethylene glycol monolaurate and polyethylene glycol dilaurate wherein the polyethylene glycol has an average molecular weight of about 400; and (c) the propellant is selected from difluoroethane and at least one of n-butane;
isobutane and n-propane;
with the proviso that the composition is a single phase mixture after exposure to temperatures of about -20°C when the benzocaine comprises about 20% of said base.
(b) the solvent is selected from at least one of polyoxyethylene sorbitan trioleate having an average of about 20 units of ethylene oxide in the polyoxyethylene chain, polyethylene glycol monolaurate and polyethylene glycol dilaurate wherein the polyethylene glycol has an average molecular weight of about 400; and (c) the propellant is selected from difluoroethane and at least one of n-butane;
isobutane and n-propane;
with the proviso that the composition is a single phase mixture after exposure to temperatures of about -20°C when the benzocaine comprises about 20% of said base.
2. The composition of claim 1 wherein the propellant comprises about 35% to about 70% by weight of difluoroethane.
3. The composition of claim 1 wherein the solvent comprises polyoxyethylene sorbitan trioleate having an average of about 20 units of ethylene oxide in the polyoxyethylene chain and one of polyethylene glycol monolaurate and polyethylene glycol dilaurate wherein the polyethylene glycol has an average molecular weight of about 400.
4. The composition of claim 1 wherein the benzocaine comprises at least 10% of said base.
5. The composition of claim 1 which is a single phase mixture at about -20°C when the benzocaine comprises about 20% of said base.
6. The composition of claim 1 wherein the base and the propellant each comprise about 45% to about 55% by weight of the composition.
7. The composition of claim 1 comprising at least 10% benzocaine in the base; the solvent comprises polyoxyethylene sorbitan trioleate having an average of about 20 units of ethylene oxide in the polyoxyethylene chain and polyethylene glycol monolaurate wherein the polyethylene glycol has an average molecular weight of about 400; and the propellant comprises difluoroethane and n-butane.
8. The composition of claim 1, 3 or 5 wherein the polyoxyethylene sorbitan trioleate comprises about 40% to about 60% of the solvent; the di-fluoroethane comprises about 35% to about 70% of the propellant; and the propellant comprises about 45% to about 55% of the composition.
9. The composition of claim 7 wherein the polyoxyethylene sorbitan trioleate comprises about 40% to about 60% of the solvent; the difluoroethane comprises about 35% to about 70% of the propellant; and the propellant com-prises about 45% to about 55% of the composition.
10. The composition of claim 1, 3 or 5 wherein the polyoxyethylene sorbitan trioleate comprises about 40% to about 60% of the solvent; the di-fluoroethane comprises about 35% to about 70% of the propellant; the propellant comprises about 45% to about 55% of the composition; and wherein the composition comprises about 20% benzocaine.
11. The composition of claim 7 wherein the polyoxyethylene sorbitan trioleate comprises about 40% to about 60% of the solvent; the difluoroethane comprises about 35% to about 70% of the propellant; the propellant comprises about 45% to about 55% of the composition; and wherein the composition comprises about 20% benzocaine.
12. A liquid anesthetic composition in an aerosol container comprising a single phase mixture of a water washable base of benzocaine in a solvent and a propellant wherein said base comprises by weight about 20% benzocaine, about 40% polyoxyethylene sorbitan trioleate having an average of about 20 units of ethylene oxide in the polyoxyethylene chain and about 40% polyethylene glycol monolaurate, said polyethylene glycol having an average molecular weight of about 400; said propellant comprises about a 50:50 by weight mixture of difluoroethane and n-butane; and wherein each of said base and propellant comprise about 50% of the composition.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1853579A | 1979-03-08 | 1979-03-08 | |
| US18,535 | 1979-03-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1136547A true CA1136547A (en) | 1982-11-30 |
Family
ID=21788426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000345059A Expired CA1136547A (en) | 1979-03-08 | 1980-02-05 | Aerosol anesthetic compositions |
Country Status (8)
| Country | Link |
|---|---|
| KR (1) | KR830001642A (en) |
| CA (1) | CA1136547A (en) |
| CY (1) | CY1310A (en) |
| GB (1) | GB2046093B (en) |
| HK (1) | HK85085A (en) |
| KE (1) | KE3558A (en) |
| MY (1) | MY8600371A (en) |
| SG (1) | SG66285G (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5766573A (en) * | 1988-12-06 | 1998-06-16 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
| US5225183A (en) * | 1988-12-06 | 1993-07-06 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
| GB8828477D0 (en) * | 1988-12-06 | 1989-01-05 | Riker Laboratories Inc | Medical aerosol formulations |
| US5439670A (en) * | 1989-11-28 | 1995-08-08 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
| DE4003270A1 (en) | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | NEW SPEED GASES AND THEIR USE IN MEDICINE PREPARATIONS |
| EP0536235B1 (en) * | 1990-06-29 | 1997-01-22 | FISONS plc | Pressurised aerosol compositions |
| GB9103302D0 (en) * | 1991-02-16 | 1991-04-03 | Smithkline Beecham Plc | Pharmaceutical formulations |
| NZ244439A (en) * | 1991-09-25 | 1994-01-26 | Fisons Plc | Pressurised aerosol compositions comprising hydrofluoroalkane, dispersed |
| 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 |
| US6129905A (en) * | 1997-04-21 | 2000-10-10 | Aeropharm Technology, Inc. | Aerosol formulations containing a sugar as a dispersant |
| US6458338B1 (en) | 1998-09-22 | 2002-10-01 | Aeropharm Technology Incorporated | Amino acid stabilized medicinal aerosol formulations |
-
1980
- 1980-02-05 CA CA000345059A patent/CA1136547A/en not_active Expired
- 1980-03-07 KR KR1019800000950A patent/KR830001642A/en unknown
- 1980-03-07 GB GB8007867A patent/GB2046093B/en not_active Expired
- 1980-03-07 CY CY1310A patent/CY1310A/en unknown
-
1985
- 1985-09-09 SG SG66285A patent/SG66285G/en unknown
- 1985-09-12 KE KE3558A patent/KE3558A/en unknown
- 1985-10-31 HK HK850/85A patent/HK85085A/en not_active IP Right Cessation
-
1986
- 1986-12-30 MY MY371/86A patent/MY8600371A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK85085A (en) | 1985-11-08 |
| GB2046093A (en) | 1980-11-12 |
| CY1310A (en) | 1986-03-28 |
| KR830001642A (en) | 1983-05-18 |
| SG66285G (en) | 1986-06-13 |
| GB2046093B (en) | 1983-04-20 |
| KE3558A (en) | 1985-10-04 |
| MY8600371A (en) | 1986-12-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |