GB1576935A - Aerosol propellants - Google Patents

Description

(54) AEROSOL PROPELLANTS (71) We, W. R. GRACE & CO., a Corporation organised and existing under the laws of the State of Connecticut, United States of America, of.62 Whittemore Avenue, Cambridge, Massachusetts 02140, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: This invention relates to aerosol propellants.

The task of finding acceptable replacements for the widely used halocarbon aerosol propellants is not an easy one. Over the years, most compounds capable of generating the necessary pressures under packing conditions have been tried, and the industry has settled, for reasons of performance, safety and cost, on a relatively limited number of gaseous liquefiable hydrocarbons, chlorofluorocarbons and a few other common non-toxic gases such as nitrous oxide and carbon dioxide.

Until recently, chiorofluorocarbons such as propellant 11 (trichloromonofluoromethane) and propellant 114 (dichlorotetrafluoroethane), in particular, appeared ideally suited for aerosol propulsion in terms of stability, chemical inertness, compatibility with aerosol package ingredients, lack of toxicity and pressuregenerating capacity. While they do benefit from this excellent combination of physical and chemical properties, their continued use in the aerosol pack area is being increasingly challenged because of their alleged deleterious effect on the layer of ozone in the upper atmosphere. In these circumstances, the search for acceptable substitutes has become imperative.Gases must be located that possess essentially the same assortment of properties as the chlorofluorocarbons but are free of chlorine which is believed to be responsible for the ozone attack.

In this respect, a review of chlorine-free, stable compounds capable of generating the necessary pressures has not proved very fruitful.

For instance, the use of dimethyl ether as aerosol propellant has been proposed but the extreme flammability of this compound, however, accounts for its lack of favour over the years even though attempts have been made to circumvent part of its disadvantages by using it together with an aqueous aerosol phase. The possibility of altering this undesirable facet of what might otherwise be an acceptable propellant in particular by fluorination, is not promising. In terms of chemical stability, it is known that halogenation of the alphacarbon of methyl ethers causes instability in the molecule.

Thus, compounds such as CHF2.O.CH3 decompose either on standing or on distillation, CH2F.O.CHF2 decomposes in glass, while other fluorinated methyl ethers are unstable under hydrolytic conditions such as may be found in aerosol preparations. The fluorinated methyl ethers did not therefore appear very promising for this reason.

More importantly, from the point of view of ecology, safety and health, it must be realised that whatever limited knowledge was available on the physiological properties of fluorinated ethers was certainly not conducive to the selection of such compounds for use as propellants in aerosol packaging, especially of personal products such as toiletries and medicinals. Thus Larsen on page 20 of Fluorine Chemistry Rev., Vol. 3 (1969) stated that "as a class, fluorinated ethers show the widest spectrum of unpredictable biological response, with some being extremely potent convulsants while others are excellent anesthetics." Obviously, neither of these properties has any appeal for the contemplated uses.A striking illustration of what can be expected from fluorinated ethers in general is afforded by the fact that bis (2,2,2-trifluoroethyl)-ether, a compound very closely related chemically to those of the present invention, can evoke seizures in rats at concentrations as low as 30 parts per million (weight/volume). It is interesting to note also that this particular diethyl ether finds use as a therapeutic convulsant in mental therapy [see Goodman & BR< Gilman, The Pharmaceutical Basis of Therapeutics, 4th Edition, pages 355-6, The Macmillan Co. (1970)1.

It has now been discovered, according to the present invention, that bis(difluoromethyl)ether and perfluorodimethyl ether may be used as propellants in aerosol containers in any proportion that will yield useful pressure. These compounds do not contain any chlorine and one would therefore not expect them to contribute to the destruction of atmospheric ozone in contrast to the conventional chlorine-containing propellant gases. Furthermore, the two compounds have been found to be stable and non-toxic, unlike other known fluorinated methyl ethers. Accordingly, the present invention provides an aerosol container containing, as propellant, bis(difluoromethyl)ether or perfluorodimethyl ether or a mixture thereof.The invention also provides a process for pressurising an aerosol container with a propellant which comprises introducing therein, as propellant, bis(difluoromethyl)ether or perfluorodimethyl ether or a mixture thereof.

The compounds used in the present invention are symmetrical dimethyl ethers in which at least two of the hydrogen atoms of each methyl group have been replaced by fluorine atoms.

The two compounds used have been found to possess the correct combination of physical, chemical and biological properties which allows their use in aerosol packaging. They are substantially stable on storage, resistant to alkaline hydrolysis and not flammable, even in direct contact with a torch. Their boiling points are -2" and -55 C for the bis(difluoromethyl)ether and the perfluorodimethyl ether respectively, which corresponds to vapour pressures ranging from 20 to 210 psig under standard conditions of temperature and pressure.

The two compounds can be obtained by, for example, electrolytic fluorination of dimethyl ether using liquid hydrogen fluoride (see, for example, United States Patents No.

2,500,388 and 3,511,760).

In preparing an actual aerosol package, the desired pressure can be achieved by mixing one or more of these propellants with other liquids (if any) involved in the aerosol preparation in whatever proportions are indicated by the conditions at hand. The propellants used in this invention may also be used together with other conventional gaseous aerosol propellants in order to achieve changes in compatibility with specific aerosol preparation ingredients, cost and rate of delivery, for example. Among such usable propellants are conventional gases such as nitrous oxide, carbon dioxide, nonhalogenated hydrocarbons as well as fluorohydrocarbons, preferbly, in order not to destroy a principal object of the present invention, those that do not contain any chlorine atoms; typically a mixture of bis (difluoromethyl) ether and carbon dioxide is used.Suitable liquid carriers for the product to be dispensed, which affects the ultimate vapour pressure include conventional materials such as ethyl alcohol, perchloroethylene, tri chloroethylene, acetone, amyl acetate and water. The dimethyl ether generally represents up to 50% by weight of the propellant. If the propellant is bis(difluoromethyl) ether it may be mixed with, for example, denatured ethanol in a weight ratio of about 50:50.

It will be evident to the man skilled in the art that the aerosol pressurising systems disclosed here can be employed with a large number of conventionally aerosol packaged materials, in particular those for personal use.

They can be used with, for example, toiletries, household and personal hygienic products, pharmaceuticals and medicines, and generally any other type of product generally packed with the conventional chlorofluoroalkanes, especially when the mode of use of such product involves a toxicity potential for living species. Specific examples of aerosol packs in which the present propellants hold particular promise include such products as hair sprays, shaving preparations, colognes, perfumes, drugs for respiratory relief, antibiotics, anti perspirants and household insecticides.

Furthermore, in many instances, in terms of compatibility with both organic and inorganic materials, the ethers used in the present invention are superior to the oxygen-free molecules of the chlorofluoroalkanes.

In addition to the properties already described for the ethers, it should be noted that at the concentrations likely to be encountered when aerosol products with which they are packed are dispensed, substantially no deleterious physiological effects take place. The compounds are not toxic and do not cause convulsions. In terms of anesthetic effects, their behaviour ranges from mild activity on two-hour exposure in mice for the tetrafluoro homologue to no activity at all for the hexafluoro homologue. The active species, the tetrafluoro compound, compares favourably with plain dimethyl ether in that it has a greater safety margin than the latter, as indicated by the standard anesthetic index (A.I.) value for each compound, said values being > 3 and 1.3, respectively (as demonstrated below).

In view of the known chemical instability of ethers in which hydrogen atoms on the alpha-carbon have been replaced by fluorine atoms, an instability which yields toxic products such as hydrogen fluoride for example, and also in view of the number of known fluorinated dialkyl ethers which cause convulsion when administrated to mammals in small concentrations, the ethers used in this invention were tested for biological activity.

The conventional tests that were carried out yielded the following data: BIOLOGICAL TESTING OF FLUORINATED ETHERS Bis(difluoromethyl)ether Mice were exposed to various concentrations of the ether in a chamber equipped with a bed of soda lime to absorb carbon dioxide. The procedure used is standard for evaluation of inhalation anesthetic and is similar to that of Robbins [Pharmacology and Experimental Therapeutics 86, 197 (1946)] Ten mice were exposed to each concentration tested for a period of two hours. It was thus determined that bis(difluoromethyl)ether is anesthetic but not toxic at concentrations of up to slightly more than 20% by volume and that the recovery time of mice anesthetised with the material is about 2 minutes. No deaths were observed during and after exposure at those levels.The anesthetic index of the tetrafluoromethyl ether was determined to be > 3 which compares favourably, from the safety point of view with that of dimethyl ether (1.3). The safety of the fluorinated ether was further determined by exposing rats to a 5% concentration during 3 hours a day for 5 days, with no signs of convulsions nor deaths being noted.

Perfluorodimethyl ether This compound was tested by exposing 6 mice to a concentration of vapours as high as 75% by volume for a period of 60 minutes. No recognisable biological effect was noted during and after exposure. This is quite different from the behaviour of the hexafluorodiethyl ether discussed in the prior section which causes convulsions in rats at 30 ppm.

Pen tafluorodimethyl ether This compound was tested for comparative purposes, again by exposing six mice to various vapour concentrations for a period of 60 minutes. All mice died either within 75 minutes of exposure or by the next morning when concontrations of 50, 25 and 12.5% were used. No discernable effects were noted at 6 and 9% vapour concentrations. Upon autopsy, it appeared that the mice died of pulmonary edema. Stable concentrations of the ether during the test and the results of gas chromatography monitoring the vapours substantially ruled out the presence of both initial impurities and later breakdown or metabolic products of the ether.

The picture that emerges from these tests is that the two ethers with which this invention is concerned are surprisingly different from most such alkyl ethers, and especially from the pentafluorodimethyl ether which has recently been said to have some utility in an azeotropic mixture with dimethyl ether. However, as the data just disclosed shows, that pentafluoro compound is not suited for use in aerosolized personal products, such as toiletries and medicines, which must frequently come in intimate contact with the user in order to be effective.

The following Examples further illustrate the present invention. Unless otherwise noted, all proportions used are on a weight basis. Also in each preparation the propellant, the ethyl alcohol and the aerosol can are cooled to -25 C to facilitate the loading operation.

EXAMPLE 1 A mixture consisting of 9.01% perfluorodimethyl ether and 90.99% bis(difluoromethyl) ether was formed and showed a vapour pressure of 36 psig at room temperature. Adding this mixture, 55.5 g, to denatured ethanol, 55 g, yielded a vapour pressure of 26 psig. When transferred to an aerosol can fitted with a valve assembly, it provided a fine aerosol spray on activation of the valve.

EXAMPLE 2 A mixture consisting of 23.08% perfluorodimethyl ether and 76.92% bis(difluoromethyl) ether had a vapour pressure of 50 psig when tested by puncturing the bottom of an aerosol can with a special pressure gauge.

EXAMPLE 3 A mixture consisting of 50.4% dimethyl ether and 49.57% bis(difluoromethyl)ether was found to have a vapour pressure of 40 psig.

When this mixture, 46 g, was placed in an aerosol can with denatured ethanol, 45 g, giving a 1:1 mix, a fine aerosol spray chould be produced.

Mixtures of this type are particularly suitables as propellants for inhaled aerosols. These are metered and of small capacity, so that the flammability and abuse potential of dimethyl ether are not of concern. The technique, on the other hand, renders available the virtues of dimethyl ether, namely its benign action on the heart, a vapour pressure sufficiently high (62 psi at room temperatures) to permit blending with bis(difluoromethyl) ether, and, because of solvent capacity, a probably high compatability with drugs.

EXAMPLE 4 Bis(difluoromethyl)ether, 23.1 g, was added to denatured ethanol, 26.7 g. The resulting mixture had a vapour pressure of 5 psig.

Despite this low pressure value, an aerosol system activated by this mixture formed a good aerosol spray.

This particular type of low pressure formulation is singularly suitable for pressurising glass-contained aerosol systems such as are preferred for esthetic reasons for dispensing perfumes, colognes and other toiletries.

EXAMPLE5 A mixture consisting of 27.32% perfluorodimethyl ether and 72.68% bis(difluoromethyl) ether was made up in a metal cylinder. The pressure of the system was found to be 75 psig.

The tetrafluoromethyl ether used in this Example contained a significant quantity of a trifluoroethane which served to raise the vapour pressure of the mixture above the value to be expected from the ethers alone.

EXAMPLE 6 Again, perfluorodimethyl ether was mixed with bis(difluoromethyl)ether in proportions of 22.2% to 77.80% respectively. The tetrafluoro ether used was that of Example 5, i.e. containing a significant quantity of a trifluoroethane. The propellant mixture 107.2 g, was placed into an aerosol can with an equal weight of denatured ethanol, the can was fitted with a valve and sealed. A good aerosol spray was obtained on activation. On puncturing the can with a pressure gauge, a reading of 56 psig was observed.

EXAMPLE 7 A 3% by weight solution of sorbitan trioleate was made in bis(difluoromethyl)ether.

There appeared to be no miscibility problems.

Sorbitan trioleate is commonly used as a vehicle for pharmaceutical aerosols such as, for instance, isoproterenol -sulphate.

EXAMPLE 8 A fragrance aerosol was prepared in a glass bottle, using the following ingredients: Weight Fragrance oil 2.5% Ethanol, 95% 47.5% Bis(difluoromethyl) ether 47.5% Perfluorodimethyl ether 2.5% A good spray was produced and, after one month storage, no change in colour or odour could be observed.

WHAT WE CLAIM IS: 1. An aerosol container containing, as propellant, bis(difluoromethyl)ether or perfluorodimethyl ether or a mixture thereof.

2. A container according to claim 1 in which the propellant further comprises nitrous oxide, carbon dioxide or a non-halogenated hydrocarbon or fluorohydrocarbon propellant.

3. A container according to claim 2 in which the propellant comprises a mixture of bis (difluoromethyl) ether and carbon dioxide.

4. A container according to claim 1 or 2 which contains a mixture of bis(difluoromethyl) ether and perfluoromethyl ether.

5. A container according to any one of claims 1 to 4 wherein the propellant comprises up to 50% by weight of the dimethyl ether.

6. A container according to claim 1 or 2 wherein the propellant is bis(difluoromethyl) ether which is mixed with denatured ethanol ethanol in a weight ratio of about 50:50.

7. A container according to any one of the preceding claims which contains at least one of the ethyl alcohol, perchloroethylene, trichloroethylene, acetone, amyl acetate and water.

8. A container according to any one of the preceding claims which contains, as active ingredient, a toiletry, hygienic preparation or pharamaceutical.

9. A container according to any one of the preceding claims which contains a hair spray.

10. A container according to any one of claims 1 to 8 which contains a shaving preppartion.

11. A counter acording to any one of claims 1 to 8 which contains an anti-perspirant.

12. A container according to any one of claims 1 to 8 which contains a household insecticide.

13. A container according to claim 1 substantially as hereinbefore described.

14. A container according to claim 1 substantially as described in any one of the Examples.

15. A process for pressurising an aerosol container with a propellant which comprises introducing therein, as propellant, bis(difluoromethyl)ether or perfluorodimethyl ether or a mixture thereof.

16. A process according to claim 15 substantially as hereinbefore described.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (16)

**WARNING** start of CLMS field may overlap end of DESC **. with bis(difluoromethyl)ether in proportions of 22.2% to 77.80% respectively. The tetrafluoro ether used was that of Example 5, i.e. containing a significant quantity of a trifluoroethane. The propellant mixture 107.2 g, was placed into an aerosol can with an equal weight of denatured ethanol, the can was fitted with a valve and sealed. A good aerosol spray was obtained on activation. On puncturing the can with a pressure gauge, a reading of 56 psig was observed. EXAMPLE 7 A 3% by weight solution of sorbitan trioleate was made in bis(difluoromethyl)ether. There appeared to be no miscibility problems. Sorbitan trioleate is commonly used as a vehicle for pharmaceutical aerosols such as, for instance, isoproterenol -sulphate. EXAMPLE 8 A fragrance aerosol was prepared in a glass bottle, using the following ingredients: Weight Fragrance oil 2.5% Ethanol, 95% 47.5% Bis(difluoromethyl) ether 47.5% Perfluorodimethyl ether 2.5% A good spray was produced and, after one month storage, no change in colour or odour could be observed. WHAT WE CLAIM IS:

1. An aerosol container containing, as propellant, bis(difluoromethyl)ether or perfluorodimethyl ether or a mixture thereof.

2. A container according to claim 1 in which the propellant further comprises nitrous oxide, carbon dioxide or a non-halogenated hydrocarbon or fluorohydrocarbon propellant.

3. A container according to claim 2 in which the propellant comprises a mixture of bis (difluoromethyl) ether and carbon dioxide.

4. A container according to claim 1 or 2 which contains a mixture of bis(difluoromethyl) ether and perfluoromethyl ether.

5. A container according to any one of claims 1 to 4 wherein the propellant comprises up to 50% by weight of the dimethyl ether.

6. A container according to claim 1 or 2 wherein the propellant is bis(difluoromethyl) ether which is mixed with denatured ethanol ethanol in a weight ratio of about 50:50.

7. A container according to any one of the preceding claims which contains at least one of the ethyl alcohol, perchloroethylene, trichloroethylene, acetone, amyl acetate and water.

8. A container according to any one of the preceding claims which contains, as active ingredient, a toiletry, hygienic preparation or pharamaceutical.

9. A container according to any one of the preceding claims which contains a hair spray.

10. A container according to any one of claims 1 to 8 which contains a shaving preppartion.

11. A counter acording to any one of claims 1 to 8 which contains an anti-perspirant.

12. A container according to any one of claims 1 to 8 which contains a household insecticide.

13. A container according to claim 1 substantially as hereinbefore described.

14. A container according to claim 1 substantially as described in any one of the Examples.

15. A process for pressurising an aerosol container with a propellant which comprises introducing therein, as propellant, bis(difluoromethyl)ether or perfluorodimethyl ether or a mixture thereof.

16. A process according to claim 15 substantially as hereinbefore described.