US 2605087 A
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y 29, 71952 DAUTREBANDE 2,605,087
' APPARATUS FOR OBTAINING AEROSOLS Filed July 27, 19 8 INVENTOR. LUCIEN DAUTREBANDE -l IS AT TORN EYS- Patented July 29, 1952 UNITED STATES PATENT OFFICE 2,605,087 7 APPARATUS non OBTAINING AEROSOLS Lucien Dautrebande, Washington, D. 0., assignor to Aerosol Corporation of America, New York, N. Y., a corporation of Delaware Application July 2'7, 1948, Serial No. 40,946
' most passages or zones in the lungs (alveoli). For
this purpose, aerosols of not over 0.5 micron mean particle size are to be preferred, and in general the aerosols should be substantially free of particles of more than 1 micron diameter. The larger aerosol particles attract the smaller ones, they tend to deposit in the nasal and throat passages, and in some instances such deposit leads either to serious difficulties or to a lack of effectiveness of the substances dispersed.
In accordance with the invention, it has been found that aerosols of a mean particle size of not over 0.5 micron may be obtained readily by means of a convenient apparatus.
One of the objects of the invention is to produce improved aerosols having a mean particle size of not over 0.5 micron. Anotherobject of the invention is the provision of apparatus for obtaining improved aerosols. Other objects of the invention will be apparent as details or embodiments of the invention are set forth hereinafter.
In accordance with the invention, a liquid is dispersed by means of a compressed gas, such as air, to form a cloud of stable and unstable dispersed liquid particles in the gas, and the cloud is directed upwardly and passed into a turbulent body of liquid, then into a non-liquid zone; and preferably then into a jet energized by compressed air to crack aggregates of liquid particles, and then directed onto a baflle plate and then out of the aerosol generator. Generally, the aerosol resulting from the atomizing jet and the turbulent body of liquid has a mean particle size of 0.50 micron, whereas that resulting from the atomizing jet plus the turbulent body of liquid followed by the cracking jet has a mean particle size of 0.36 micron. This is true for an aqueous solution, regardless of the molecular weight or concentration of solute Within usual concentration ranges suitable for aerosol therapy, e. g., 1 to by weight of therapeutic agent.
Referring to the drawing, Figure 1 illustrates 1 Claim. (Cl. 261-21) 2 an apparatus suitable for carrying out the method of the invention, partially in section and partially in elevation.
Figure 2 shows a cross-sectional view along the lines 22 of Figure 1.
The vessel I is provided with a liquid reservoir at the bottom, preferably detachably connected,
e. g., by screw threads, for holding the liquid to be dispersed 5, a jet member made up of air inlet 3 and liquid supply tube 4 which extends into the liquid to be dispersed. A frusto-conical member 6 is provided directly over the aerosol generating zone 2. An optional skirt baffle member I0 may be suitably mounted within conical member 6, and in addition an optional screen or foraminous member I I may be provided across the lower opening of the conical member. The upper or narrow end of member 6 may optionally fit into a jet member having an air inlet tube 3A.
vided, having openings or slits near the periphery thereof, to permit the aerosol to pass to exit 9, at the top of vessel I. I
Figure 2, a cross-sectional view along the lines 22 of Figure 1, shows the space, e. g., 2-3 mm. distance, between the upper edge surface of the optional cylindrical skirt member ID and the conical member 6. It, also shows three jet apertures in the jet assembly.
The total free area across the bottom of member 6 preferably equals the cross-sectional area of outlet member 9, The total cross-sectional area of the openings near the periphery of mem her I, and also the total cross-sectional area of the openings in baffle member 8 each preferably equal the cross-sectional area of member 9. If any one of these areas is smaller than the exit crosssecticna1 area above it, there will tend to be a positive pressure differential, impeding efiicient operation of the jets. If any one of these areas is larger than the exit area, there will tend to be poor eiliciency in eliminating the larger size liquid particles. Generally, the diameter of exit member 9 is of the order of 1 to 3 cm., and the diameter of vessel I is about five timesthat of member 9. The conical member 6 has a total angle at the maximum longitudinal section in the range of 30 to 50, and. the height of member 6 is of the order of to 8 cm. The length of the skirt member H] is of the order of A1. to /3 the the height of member 6. Preferably, the distance between the upper edge of member l0 and member 6 is of the order of 1 to 3 mm. Generally, member 1 will be about the same height as member 6, but of a larger total angle, so as to reach across the complete cross-sectional area of vessel I.
4 to reduce the mean particle size of the final aerosol.
Each of the jet members may have one, two or three sets of air and liquid apertures, three each being shown in the drawings. For example, the lower jet member may have one set of apertures and the upper jet member three sets, or viceversa, or 2 by 2. Likewise, tube 3A may have three jets, tube 3B one, tube 3 two jets and so on. The variety of combinations of air-liquid mixtures is thus very large and adaptable to any therapeutic or industrial requirements.
If desired, vessel 1 may be elongated, and provided with additional assemblies of frusto-conical members and jet assemblies similar to I and 33,
below baffle member 8. If desired, .vessel' I may f be made up of sections, which may be joined by suitable means, e. g., by screw threads, each section having a frusto-conical member and an air inlet member similar to l and 3B, e. g., upto twelve such sections. Where there are several members similar to 'i and 313, an aerosol outlet member, provided with a suitable valve, may be provided in the sidewall intermediate each of these conical and jet assembly members for takim; off aerosols of desired mean particle size or of desired concentration of liquid particles in the gas.
It desired, the liquid reservoir in vessel I may have a conical shaped bottom, or be provided with a suitable feeding device for maintaing constant level of liquid therein, or it may be provided with means for continually removing liquid therefrom and replacing it'with solution of controlled concentration. If desired, the liquid to be dispersed may be fed directly under pressure into tube 4,
e. g., from an outside supply through suitable connections, not shown. 1
In operation, compressed air or other suitable gas is introduced into tube 3 under such conditions that liquid will be drawn up through tube 4 and dispersed in the form of a cloud or a mist at zone 2 and impelled upwardly into the member 6, no air or gas being introduced in tube 3A. Conditions are selected so that the cloud passing into member 6 contains a substantial amount of unstable liquid particles, which coalesce and form a very turbulent liquid body in the member 6. This liquid body is maintained in dynamic equilibrium, e. g., by balancing the amount of liquid supplied thereto against the amount running downward therefrom. In this turbulent'liquid body, the larger and unstable liquid particles are removed'from the cloud, and the resulting aerosol passed around the lower edge of member 6 and upward into member I. Compressed air is introduced through tube 3B. This will draw the aerosol from within member I and form and direct a jet of aerosol against bafile member 8; and the resulting aerosol then passes through the openings in member 8 to the exitin member 9. A relatively small portion of the aerosol may pass through the apertures in member 1 and there may be a liquid film formed across the apertures in member 1, due to coalescence of relatively'unstable liquid particles, and this fihn willjte'nd to remove unstable particles from zerosol passing therethrough.
' If desired, compressed air may be introduced through tube 3A, and this will enrich or increase the concentration of stable particles in the aerosol passing into member I.
Member 1 serves to break up agglomerates of liquid particles which are not coalesced, and also In general, the size of the apertures is preferably such as to deliver a rate of air flow per aperture in the range of to liters per minute,
for conventional relatively low air pressures of the order of 7 to 55 pounds per square inch gauge. For such an air flow, the rate of dispersion of liquid in the lower jet :assembly is preferablyin the range of 10 to 20 cc. per hour.
Ina typical example of low particle size aerosols and their preparation, there is used an apparatus'as illustrated in Figure l, with only one set of air and liquid apertures in the lower jet assem: bly, and having three sets o'f apertures in the upper jet assembly; no air being introduced in inlet 3A, with a 10 aqueous solution of eosin in the liquid reservoir, an air input of pounds per square inch on the upper and th lower jets, 3 and 3B. The resulting aerosols are passed into a chamber of 225 cubic meters capacity, the interior of which is maintained at atmospheric pressure. After 10 minutes, the aerosols are allowed 'to settle on collector plates, coated with a thin film of petrolatum, e.'g., foran hour, then the plates are protected by a cover, cemented at the edges, e. g., with Duco cement, and immediately examined by means of an optical microscope, e. g., with oil immersion objective and 1125 magnification. The mean particle size of the aerosolsis found to be 0.36 microns.
In another example, following the above procedure except without introducing any air into the upper jet member, 3B, the mean particle size of the resulting aerosol is 0.50 microns. This shows that the upper jet member substantially reduces the number of larger particles in the aerosol.
Aerosols of this mean particle size are obtained, using a gas inlet pressure in the range of 7 to pounds per square inch gauge, aqueous solutions of materials ofdifi'erent molecular weights, or of different concentrations within suitable therapeutic concentration ranges, e. g., l to 10% by weight of the therapeutic agent.
If desired, the mean particle size may be determined by nephelometric methods or by electron microscope means. In the latter method, there. are. observed aerosol particles which are toosmall to. be seen by means of the optical microscope, and when these are taken into consideration, the mean particle size of the aerosol will be even smaller, e. g., 0.07 microns for the. first of the above examples as compared with 0.10 microns for the second as determined after collecting, freezing and drying.
. It is known that aerosols of the size described have a tendency to form aggregates. In combating dust, these aggregates are very useful. In
some cases,however, it is desirable to avoid ag-j gregation of. the dispersed particles, mainly for penetration into the respiratory depths of very powerful pharmacologic substances. The process of cracking not only reduces theflparticle size of the discrete micellae but also prevents the formation of large aggregates. For instance, with the generator described, results obtained are summarized below:
Without cracking (i. e., without introducing air into member 3B) General mean'size micron 0.1 Percentage of particles below 0.1 micron per cent 81.1 Mean size of particles below 0.1 micron Angstrom U 566 Mean size of particles above 0.1 micron micron 0.30 Mean size of optically visible aggregates micron 2.1 Largest singleparticle do 1.4 Largest aggregate do 4.3
With cracking 1 General mean size micron 0.07 Percentage of particles below 0.1 micron per cent 84.0 Mean size of particles below 0.1 micron Angstrom U. 425 Mean size of particles above 0.1 micron micron 0.20 Mean size of optically visible aggregates micron" 0.64 Largest single particle do 0.6 Largest aggregate do 1.2
This process thus permits not only the production of smaller micellae but also considerable reduction in the size of the aggregates.
Using a lower nozzle with one jet and an upper nozzle with three jets and with an air pressure in both nozzles of 42.5 pounds per square inch gauge, the following results are obtained:
Percentage of particles below 1 micron This aerosol contains not a single aggregate and the micellary size is strikingly low and uniform. The apparatus or parts thereof may be made of glass, metal, plastic, or the like suitable material; and although various members are described as being substantially circular in cross section, other shapes may be used provided the critical relationships disclosed are retained.
The particular jet members discussed above are admirably adapted for producing aerosols. However, known types of jet members may be used, providing the resulting mist or cloud contains both very fine liquid particles and also a substantial amount of larger relatively unstable particles. The unstable particles will tend to be removed in the turbulent liquid body or in the treatments subsequent to contact with the turbulent body, or both.
The existence and maintenance of the turbulent liquid body is of great importance in carrying out my invention as disclosed herein. I have found that the formation and utilization of one or more turbulent liquid masses is critical in the production of aerosols of the preferred small size and uniformity. myriad of liquid films comprising the turbulent mass which are available to act upon the aerosols as they pass through the apparatus.
The relatively uniform aerosols of very low mean particle size, having substantially all particles of less than 1 micron maximum size, are particularly suitable for use in aerosol therapy, particularly in the treatment of the innermost passages or regions (alveoli) in the lungs. If it is desired to simultaneously treat or medicate the nasal or throat passages, larger mean particle size aerosols, having some particles of the order of 1 to 5 microns diameter, may be used.
The aerosols produced in accordance with the invention may be suitable for other uses, e. g., precipitation or agglutination of very fine dust particles, which dust particles are so fine that they pass through a liquid layer, through the nasal and throat passages, and into the innermost regions of the lungs where they may deposit and produce very undesirable effects, e. g., silicosis. The very fine aerosol particles tend to agglomerate and coalesce with the very fine dust particles, to produce larger size particles which may be precipitated or settled.
In view of the foregoing disclosures, variations and modifications thereof will be apparent to those skilled in the art, and all such variations and modifications are broadly contemplated within the invention.
In an apparatus for producing an improved aerosol, a vessel provided with a liquid reservoir, atomizing means comprising a liquid feed tube in communication with the said reservoir and an upwardly directed air inlet tube, a first frus-toconical member set axially about vertically above said atomizing means, a skirt baiile member within said first frusto-conical member, a fine meshed screen across the larger end of said first frusto-conical member, a second and larger frusto-conical member set above said first mem- V ber and dividing said vessel into an upper and a lower zone, said second member being apertured near the periphery thereof, the narrow end of said second member communicating with a second atomizing means, a baffle member set above said second atomizing means, and an aerosol outlet tube.
REFERENCES CITED The following references are of record in the file of this patent:
UNITED STATES PATENTS This may be due to the