|Publication number||US3584115 A|
|Publication date||Jun 8, 1971|
|Filing date||May 31, 1968|
|Priority date||May 31, 1968|
|Publication number||US 3584115 A, US 3584115A, US-A-3584115, US3584115 A, US3584115A|
|Inventors||Bonduris Angelo Thomas, Gebhart Arthur Ira|
|Original Assignee||Bonduris Angelo Thomas, Gebhart Arthur Ira|
|Export Citation||BiBTeX, EndNote, RefMan|
|Referenced by (40), Classifications (27)|
|External Links: USPTO, USPTO Assignment, Espacenet|
United States Patent Othce 3,584,115 METHOD OF APPLYING VISIBLE AEROSOL COMPOSITIONS Arthur Ira Gebhart, 109 Oakwood Drive, Largo, Fla. 33540, and Angelo Thomas Bonduris, 57 Ross Ave., Metuchen, NJ. 08840 No Drawing. 'Continuation-in-part of application Ser. No. 561,738, June 30, 1966. This application May 31, 1968, Ser. No. 733,263
Int. Cl. A61k 9/00 US. Cl. 424-45 '9 Claims ABSTRACT OF THE DTSCLOSURE Pressurized topical compositions exhibiting the property of becoming substantially colorless under ambient temperature conditions comprising a major proportion of a liquefied normally gaseous propellant and a minor proportion of a mixture of C C fatty alcohols and Wherein at least 50% by weight of said fatty alcohol mixture comprises a C -C fatty alcohol.
The present invention relates in general to compositions specifically and advantageously adapted for dispensing by propellant from pressurized containers and in particular to the provision of improved topical compositions for such purposes.
The present application is a continuation-in-part of US. 561,738 filed June 30, 1966, now abandoned.
As is well-known, the provision of compositions beneficially adapted for use in connection with aerosol applications has assumed considerable commercial importance and particularly in view of the manifold advantages inherent in aerosol dispensing vis a vis more conventional methods as typified by pad, roller application, and the like. Aerosol dispensing affords the significant advantage that more highly efficient utilization of product is obtainable, i.e., more area can be treated with a given amount of product than is possible with other methods of dispensing.
The advantages made possible by aerosol dispensing methods have been exploited in connection with a relatively wide variety of applications including, for example, analgesic compositions adapted to locally desensitize the human body whereby to relieve a patient from certain types of pain stress and discomfort, as well as numerous compositions adapted to perform primarily an antibiotic function, e.g., to provide therapeutic relief in the case of burns, abrasions or other wounds. Compositions adapted for the foregoing purposes are usually provided with one or more medicants capable of performing the requisite antibiotic function. It will be understood that application to human skin may be for other than therapeutic, as, for example, the depositing of sun-screening compositions whereby to promote tanning, to provide protection against insects, e.g., repellent compositions, etc.
Regardless of the particular utility contemplated for the aerosol composition in question, it is in many instances essential that the product composition be capable of ready visual discernment, substantially immediately upon dispensing in order to permit ready visual comprehension as to the extent of the area being subjected to treatment. Compositions of this type are often characterized as being topical being specifically and beneficially adapted for local application to a given surface. It will be Patented June 8, 1971 recognized, of course, that the surface being treated may constitute substances other than human skin; thus, the aerosol product in question may be adapted for application to fabrics, walls, floors and the like as in the case of cleaning and stain removing compositions.
Heretofore, it has been a recognized practice to incorporate in topical compositions one or more materials specifically adapted to impart thereto the property of forming a visually detectable color or hue upon dispensing to a surface. Materials thus far promulgated in the art for such purposes include, for example, pigments, powders and the like in particulate form capable of being deposited in the form of a visible film. Although compositions so constituted have proved somewhat satisfactory for the vast'majority of aerosol applications, their use is nevertheless accompanied by one or more serious objections tending to detract from their commercial desirability. Perhaps the primary objections are attributable to the tendency of such pigment materials to remain upon the treated skin area for extended periods of time in visible form. As will be appreciated, the topical composition in question may well present the appearance of a stain; such a condition is highly undesirable since the deposit thus persisting may be extremely aesthetically displeasing. In addition, problems are frequently encountered in connection with the provision of the pigment-containing composition in the form of a uniform and homogeneous dispersion having the requisite particle size. It is self-evident, of course, that each of the solid components present in the aerosol composition must be of a particle size which permits their ready dispensing through a spray orifice of conventional design. It is further imperative that the composition be totally devoid of any tendency to form needle-like substances since the latter can serve to matter or clog the spray orifice. Consequently, it is encumbent upon the formulator when preparing aerosol compositions containing one or more pigment or powder materials to provide the latter in finely triturated form in order to ameliorate the aforedescribed and related problems. In many instances, resort to the use of special solvents or other materials serving to expedite homogeneous dispersion of the involved ingredients is necessitated thereby presenting problems which may well be prohibitive from a handling and economic standpoint.
Other factors which tend to militate against the use of pigment materials in topical, aerosol compositions arise from the limitations imposed upon the processor as re gards selection of co-ingredients. Accordingly, the propellant and/ or solvent employed must of necessity be one which tends to suppress crystal growth of contained solid particles upon standing. Departures from the aforedescribed requirements may well result in an aerosol product subject to wide variations in viscosity, particle size, etc., thereby rendering efiicient dispensing of the aerosol ingredients extremely difficult if not practically impossible.
In an effort to overcome or otherwise mitigate the aforedescribed and related problems considerable industrial activity has centered around the'research and development of means whereby to render compositions suitable for aerosol dispensing in connection with topical applications and wherein problems of the aforedescribed nature are substantially eliminated.
In accordance with the discovery forming the basis of the present invention, it has been ascertained that aerosol compositions beneficially adapted for local application to a surface, i.e., topical compositions may be synergistically modified to advantage by including therein as essential addenda a mixture of fatty alcohols selected from a relatively limited class of materials.
Thus, the primary object of the present invention resides in the provision of topical compositions beneficially and advantageously adapted to be dispensed by propellant from pressurized containers wherein the aforedescribed and related problems are eliminated or at least mitigated to a substantial extent.
Another object of the present invention resides in the provision of aerosol topical compositions capable of being deposited in the form of a visually detectable film whereby to promote ready visual discernment of the area being treated.
A further object of the present invention resides in the provision of aerosol topical compositions capable of depositing films which exhibit the property of becoming substantially colorless under ambient temperature conditions.
A still further object of the present invention resides in the provision of aerosol topical compositions wherein any necessity for the use of pigment or related materials is completely obviated.
Other objects and advantages of the present invention will become apparent hereinafter as the description proceeds.
The attainment of the foregoing and related objects is made possible in accordance with the present invention which in its broader aspects includes the provision of pressurized topical compositions capable of depositing a visually detectable film upon discharge from the containing package said film exhibiting the property of becoming substantially colorless under ambient temperature conditions, said composition comprising a major proportion of a liquefied normally gaseous propellant and a minor proportion of a mixture of C to C fatty alcohols and wherein at least 50% by Weight of said fatty alcohol mixture comprises a C to C fatty alcohol.
The pressurized topical compositions of the present invention are uniquely characterized in their capability of depositing a visually perceptible film material to a surface, the film in question assuming substantially colorless form when the temperature in the immediate environs of said film approximates ambient conditions. In this manner the objectionable features invariably attending the use of pressurized compositions containing pigment, e.g., the tendency of such compositions to form unsightly deposits of a relatively permanent nature are completely eliminated. In contrast to analogous compositions heretofore promulgated in the art, the topical compositions of the present invention exhibit the property of rapidly melting when subjected to ambient temperature conditions. Thus, and with specific reference to applications to human skin, the aerosol composition as sprayed provides a film deposit having an initial whitish coloration thereby enabling the user to precisely determine the extent of the area being treated. As will be readily evident, the temperature of the aerosol composition when sprayed is considerably below that of the human skin. In fact, the instant compositions are primarily adapted for application to surfaces which would, in the ordinary course of events, be maintained under ambient temperature conditions. Thus, the sprayed film deposit upon warming to ambient conditions undergoes relatively rapid melting, the latter being accompanied by a corresponding dissipation or extinguishing of the coloration characterizing said deposit. Accordingly, the film deposit upon substantially complete melting, assumes colorless form to the extent that any possibility of detection by the human eye is virtually eliminated.
The advantages made possible by the present invention depend vitally upon the utilization of the aforedescribed mixture of fatty alcohols within the proportions stated. Thus, it is critically imperative that the C to C fatty alcohol component comprise at least 50% by weight of the total alcohol mixture. Departures from such range will inevitably vitiate any possibility of obtaining an optimum product. As examples of C to C fatty alcohols admirably suited for use in accordance with the present invention there may be mentioned without necessary limitation the following:
pentadecyl alcohol (palmityl) hexadecyl alcohol (cetyl) heptadecyl alcohol octadecyl alcohol eicosyl alcohol (C H OH) carnaubyl alcohol (C H OH) ceryl alcohol (C H OH) melissyl alcohol (C H OH) Other alcohols found to be suitable for use herein include:
dodecyl alcohol (lauryl) tridecyl alcohol tetradecyl alcohol (Myristic) In order to assure the obtention of optimum results, it is recommended that the alcohol mixture be employed in amounts approximating at least about 7% by weight of the total pressurized composition with a range of about 9% to about 30% being found particularly beneficial. It will be further understood that the alcohol mixture involved may comprise two or more of the aforementioned materials and accordingly, the term mixture as used herein is to be so understood. However, regardless of the nature of the alcohol mixture employed, it is mandatory that the aforestipulated requirement as regards relative proportions of alcohol materials be complied with, i.e., that the C to C alcohol constitute at least 50% by weight of the mixture.
The propellant material employed in formulating the aerosol compositions of the present invention may be selected from any of those well known in the art for such purposes. Thus, the propellant comprises preferably a liquefied normally gaseous substance or mixture thereof. In general, it is preferred to use liquefied, normally gaseous, low molecular weight halogenated hydrocarbon propellants such as halogenated ethane, methane and mixtures thereof. The halogenated hydrocarbon propellants comprises a well-known class of materials being conventionally referred to as the Freons and Genetrons. Specific examples of such materials include without necessary limitation, dichlorodifluorolmethane (Freon l2), dichlorotetrafluorolethane (Freon 114), trichlorornonofluorolmethane (Freon 11) and the like.
In addition, any of the liquefied, normally gaseous, hydrocarbon propellants may be employed such as the aliphatic hydrocarbons containing from 3 to 4 carbon atoms, e.g., propane, butane, isobutane, and mixtures thereof. The propellant material provides the necessary solvent medium for the mixture of fatty alcohols.
The amount of propellant employed is not a particularly critical factor in the practice of the present invention the primary requirement with respect thereto being, of course, that such material be present in amounts sufficient to permit substantially complete expulsion of the contents, i.e., the topical composition, from the pressurized container. Thus, the particular amount required in connection with a given application will vary depending upon the requirements of the processor. In general, however, it is found that highly efiicacious compositions may be formulated with the use of the propellant in amounts ranging from about 70% to about 93% by Weight of the aerosol product.
It will be understood that the aforedescribed propellant materials may be employed either singly or in admixture depending somewhat upon the ultimate use contemplated for the composition being formulated. Thus, in those instances wherein flammability considerations are germane, it may be preferable to utilize propellants of the halogenated hydrocarbon type. In any event, the determination of optimum propellant materials as well as proportions Within the ranges specified in a particular circumstance may be readily effected according to relatively routine laboratory investigation.
The compositions of the present invention may be employed to pronounced advantage in connection with the formulation of analgesic products. In such instances, the composition may simply comprise a mixture of the propellant material and fatty alcohol system. As is well known, a particularly effective method of relieving certain types of body pain, e.g., musculoskeletal pain arising from injury to the muscle itself or to tendons comprises merely spraying the affected area with a pressurized propellant composition, e.g., one comprising mixtures of fiuorinated halo-hydrocarbons such as the aforementioned Freons and Genetrons. Methods of this type are described, for example, in an article by Dr. Janet Travell in the Archives of Physical Medicine, May 1952, volume XXXIII, pages 291-298. It is hypothesized that the propellant stream functions to desensitize the body area contacted, i.e., the threshold sensitivity level of pain is significantly reduced, thereby relieving the patient from pain and discomfort. The compositions described herein are advantageously adapted to such uses since the area subjected to the aerosol spray is manifested in the form of a visible deposit. Spraying of the skin area will invariably be accompanied by a relatively precipitous drop in temperature of the affected area. During this period of depressed temperature, the spray deposit is readily visibly detectable; however, within a relatively short period of time, the temperature characterizing the sprayed area approaches the temperature of the immediate surroundings, i.e., in the case of application to the human skin, the body temperature. During this transition period, the visible spray deposit covering the skin area melts rapidly, thereby becoming substantially invisible.
Analgesic compositions in accordance with the present invention may be readily prepared by merely first melting the normally solid fatty alcohols so as to provide a fluid mixture and thereafter introducing same to a pressurized aerosol dispenser previously charged with the propellant material. Eificacious analgesic compositions may be obtained by the use of the fatty alcohol mixture in concentrations ranging from about 7 to about 30% by weight, the remainder comprising the propellant material selected for use. Compositions so constituted afford the advantage that significant improvement in product covering power or covering efficiency is attainable, i.e., more skin area can be effectively treated than is possible with the use of ointments or, alternatively, aerosols of the foam type.
The basic ingredients of the composition herein described, i.e., the fatty alcohol mixture and propellant, lend themselves advantageously to a wide variety of diversified applications. Thus, by the incorporation of one or more medicants, antiseptics, bactericidal materials, antibiotics, etc., the composition may be rendered therapeutically effective such as for purposes of promoting the healing of burns, infections, and the like. Suitable medicants for such purposes are well known in the art and include, for example, merthiolate, an antiseptic, tyrothricin, an antibiotic, thiomerosal, an antiseptic, neomycin, the latter a powerful bactericidal and antibiotic medicant, neomycin sulfate and active neomycin salts of organic acids, e.g., caprylic, propionic and the like. Other ingredients of an optional nature include, medicinal ointments, e.g., polyethylene containing gels as well as other oleaginous ointment bases. If desired, antioxidants and preservatives for the prevention of mold growth may also be added. Other materials found to be particularly effective in the treatment of burns, wounds, lesions involving the skin of the face, elbows, sacrum, buttocks, knees, ankles, etc.; dermatitis, e.g., diaper rash, prickly heat include without necessary limitation vitamins A and D, Panthenol (d-pantothenyl alcohol), etc.
In any event, optional ingredients of the foregoing type may be present in amounts varying over a relatively wide range. Thus, in the case of medicants and other therapeutic agents, concentrations ranging from about .001% to about 2% and higher by weight of the composition are eminently suitable. Again, optimum values in this regard are largely matters of discretion depending inter alia upon the potency desired in the final product, the particular use contemplated, etc.
The propellant/fatty alcohol-containing compositions of the present invention may be further and advantageously employed in the preparation of cleaning, polishing, stain-removing, etc., formulations contemplated for use in connection with the treatment of a vast number of surfaces including fabrics, ceramics, glass, metal, wood, and the like. The preparation of such compositions may be readily and easily effected by merely including in the basic composition the desired quantities of ingredients necessary to the function or use contemplated, e.g., detergent, abrasive, polishing agent, etc.
It is thus manifestly clear that the propellant-fatty alcohol compositions are admirably suited for a vast number of uses; thus, it is envisaged that many types of ingredients may be incorporated for purposes of adapting the product composition as desired. The nature or function of the ultimate composition is not particularly critical with one major exception; namely, the composition in question must be one which would otherwise be capable of yielding a colorless, substantially water clear film upon dispensing from an aerosol container. As clearly indicated her'einbefore, the instant compositions are singularly adapted for use in topical applications, i.e., those applica tions necessarily requiring the deposition of a visibly detectable deposit and wherein it is desired that the latter be transitory or temporary in nature.
In some instances, it may also be desirable to include one or more ingredients for purposes of promoting compatibility, solubility, etc., of one or more of the af mentioned ingredients. Thus, it has been found that the conjoint use of a polyunsaturated oil, e.g., vegetable oil, is particularly valuable when formulating vitamin-containing compositions, the oil serving as a vitamin carrier while expediting the incorporation of greater quantities of the C C fatty alcohol component. The specific nature of the polyunsaturated oil is not particularly critical apart from the requirement that it be capable of deposition in colorless form when dispersed from an aerosol container. In any event, vegetable oils in general are found to be particularly preferred in this regard with suitable representatives including, without necessary limitation, corn oil, sesame oil, safflower oil, rape seed oil, cotton seed oil, etc. The proportions of polyunsaturated oil employed may range within relatively wide values. However, for the vast majority of applications, it is found that amounts falling within the range of 0.1% to 10% by Weight of the composition are eminently suitable, with a range of 0.5 to 6% being found particularly beneficial.
It may, in addition, be advisable in the preparation of medicant-containing compositions to employ one or more solvents whereby to expedite homogeneous dispersion of the involved ingredients. Thus, it has been ascertained that nontoxic polyhydric alcohols miscible with the propellant employed tend to promote more effective dissolu tion of the involved ingredients. As examples of suitable polyhydric alcohols there may be mentioned ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol glycerol, etc.
It is to be clearly understood that compositions prepared in accordance with the present invention may comprise simply a mixture of the propellant material and fatty alcohol system within the concentration stated such compositions having excellent utility in analgesic applications. Thus, the auxiliary ingredients enumerated hereinbefore are essentially of an optional nature, their use being dictated solely by the function contemplated for the aerosol composition in question. In any event, optional ingredients other than those specifically mentioned may be added so long as the salient property characterizing the aerosol compositions contemplated herein he not affected, i.e., the property of forming a temporarily visible deposit upon dispensing, such deposit becoming invisible to the naked eye upon warming to ambient temperature conditions.
The following examples are given for purposes of illustration only and should not be considered as necessarily constituting a limitation on the scope of the present invention.
EXAMPLE 1 This example illustrates the preparation of an analgesic composition comprising simply a mixture of propellant and fatty alcohols.
A mixture of fatty alcohols consisting of 60% by weight cetyl alcohol and 40% by weight myristyl alcohol is warmed until melted. The mixture is agitated in order to promote homogeneity of dispersion; approximately 10 grams of the liquefied alcohol mixture thus obtained is charged to a 4 ounce aerosol can and pressure-filled with 90 grams of a 30/70 mixture of dichlorodifluoromethane (Freon 12) and dichlorotetrafiuoroethane (Freon 114). The aerosol can is provided with a vapor tap type valve in order to ameliorate somewhat the chilling effects of the aerosol composition, whereby to minimize, if not eliminate, any possibility of freezing the skin area to be treated.
The above composition is then sprayed upon predetermined areas of the body indicated by the diagnosis of the muscular pain and discomfort in rhythmic intermittent sweeps ranging from about 5 to 15 seconds in duration, the spraying being continued for a period of about 8 minutes. In each instance, the area subjected to the aerosol spray is immediately visible due to the formation of a whitish deposit in such areas. The visible areas afiord excellent means for determining the extent of the area treated within seconds after completion of the spraying operation. The visible spray deposit totally dissappears within a matter of seconds leaving nothing in the nature of a visible residue. Moreover, the desired pain and discomfort-relieving action obtains in each instance without excess chilling or after pain.
EXAMPLES 2-8 The procedure described in Example 1 is repeated but employing in lieu of the cetyl alcohol-myristyl alcohol mixture the following:
Results similar to those described in Example 1 are obtained, i.e., the desired visible deposit of aerosol composition is obtained providing a readily visible marking area, the deposit in each instance disappearing rapidly as the temperature in the immediate vicinity of said deposit approaches ambient conditions. Moreover, the compositions provide excellent relief in the case of muscular pain and discomfort.
The following examples illustrate the preparation of vitamin-containing aerosol compositions found to be particularly effective as regards therapeutic treatment of various skin irritations such as diaper rash pricking heat, etc. In each instance the active ingredients comprise vitamins A, D and Panthenol. As'explained hereinbefore, the concentration of such ingredients may vary within relatively wide ranges. However, the attainment of optimum results is assured with the use of, for example, vitamins A and D in amounts sufficient to provide a concentration on the order of about l l0 U.S.P. units of vitamin A palmitate and l l0 U.S.P. units of vitamin D-2 per gram of deposit material. The Panthenol ingredient is preferably employed in amounts approximating 1-2% of the composition. The non-toxic dipropylene glycol employed serves to promote solubility of the Panthenol in the propellant blend.
EXAMPLE 9 The following composition is prepared.
1 1X10 U.S.P. units vitamin A per gram.
2 1 X 10 U.S.P. units vitamin D per gram.
' The above-described ingredients provide a highly effective aerosol composition for purposes of treating skin rashes, irritations, and other disorders as well as skin burns and other similar wounds.
EXAMPLE 10 Example 9 is repeated with the exception that the propellant blend employed consists of a 30/70 mixture of dichloridifiuoromethane/dichlorotetrafluoroethane (61.34% by weight of the total compositions) and trichloromonofiuoromethane (15.0% by weight of the total composition).
The results obtained are similar to those described in Example 9, i.e., the aerosol composition provides highly effective means for the treatment of skin disorders, burns, etc.
The compositions illustrated in Example 9 and 10 can be readily and easily prepared according to the following sequence of operations. The dipropylene glycol and dipanthenol are thoroughly admixed and heated to a temperature of approximately 60 C., the heating operation being preferably carried out on a water bath. Agitation of the mixture: is maintained throughout the heating operation. Heating of the mixture is continued until a clear viscous solution results, the occurrence of the latter condition marking the termination point of the heating operation. The mixture is then immediately removed from the source of heat. I
The fatty alcohol materials and polyunsaturated oil are mixed and heated until the alcohols completely melt. Agitation is maintained during the heating operation. Upon completion of heating thereis obtained a yellow, homogeneous solution.'The latter is added to the previously prepared Panthenol-dipropylene glycol solution with agitation. The vitamin A and D materials are thereafter incorporated with agitation. In each of the examples, 26.83 grams of the mixture so obtained are charged to a 4 ounce aerosol can which is then pressure filled with 86.57 grams of the propellant blend.
In accordance with preferred practice, it is desirable that the compositions possess acloud point on the order of about 68 F. and a clear point on the order of about 72 F. This condition is, of course, highly desirable as regards compositions intended primarily for application to human skin. However, it will be understood that the selection of specific values for each of such properties lies largely within the discretion of the formulator. It is found, for example, that the cloud potint of the propellant-fatty EXAMPLES 11-15 Example 9 is repeated with the exception with the cetyl alcohol/myristyl alcohol mixture is replaced with equivalent amounts of the materials specified in the following examples:
Alcohol w ht t eig re. 10 (b) 11 octadecyl Tetradeeyl 60/40 Heptadecyl Dodecyl 65/35 13- Carnaubyl "do 70/30 14 Ceryl Tetradecyl 60/40 15 Melissyl Dodecyl 75/25 In each instance the aerosol composition obtained is similar in effectiveness to those described in Examples 9 and 10.
The present invention has been described with respect to certain perfect embodiments thereof and there will become obvious to persons skilled in the art other variations, modifications and equivalents which are to be understood as coming within the scope of the present invention.
What is claimed is:
1. A method of topically applying to the skin a visible white film indicating the area of application which comprises applying to the skin a pressurized, topical aerosol composition containing as essential ingredients from 70- 93 percent of a liquified normally gaseous propellent and from 7-30 perecnt of a mixture of C -C fatty alcohols wherein at least by weight of said fatty alcohol mixture comprises C -C fatty alcohols, said white film is visible for a short period of time until the temperature characterizing the sprayed area approaches the temperature of the immediate surroundings.
2. A method according to claim 1 wherein said alcohol mixture consists of by Weight octadecyl alcohol and 40% by weight tetradecyl alcohol.
3. A method according to claim 1 wherein said alcohol mixture consists of by weight heptadecyl alcohol and 35% by weight dodecyl alcohol.
4. A method according to claim 1 wherein said alcohol mixture consists of by weight carnaubyl alcohol and 30% by weight dodecyl alcohol.
5. A method according to claim 1 wherein said alcohol mixture consists of 60% by weight ceryl alcohol and 40% by weight tetradecyl alcohol.
6. A method according to claim 1 wherein said alcohol mixture consists of by weight melissyl alcohol and 25% by weight dodecyl alcohol.
7. A method according to claim 1 wherein said alcohol mixtuer consists of 75 by weight cetyl alcohol and 25 by weight myristyl alcohol.
8. A method according to claim 1 wherein said alcohol mixture consists of by weight cetyl alcohol and 10% by weight myristyl alcohol.
9. A method according to claim 1 wherein the composition further contains from about .001 to about 2% by weight of total composition of a member selected from the group consisting of vitamin A, vitamin D, Panthenol, and mixtures thereof.
References Cited UNITED STATES PATENTS 2,983,650 5/ 1961 Rubin 424-47 2,987,438 6/ 1961 Ashkenaz 424-45 3,052,607 9/1962 Hirsh 424-343 3,095,355 6/1963 Abramson et al. 424-46 3,226,295 12/1965 Goetz et al. 424-343 ALBERT T. MEYERS, Primary Examiner N. A. DREZIN, Assistant Examiner US. Cl. X.R. 424-237, 343
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|U.S. Classification||424/45, 514/168|
|International Classification||A61K8/34, C09K3/30, A61K8/04, A61K31/16, A61K8/67, A61K8/30, A61K9/12, A61K8/42, A61Q19/00|
|Cooperative Classification||A61Q17/00, A61K9/12, C09K3/30, A61K8/67, A61K8/42, A61K8/046, A61Q19/00, A61K8/342|
|European Classification||C09K3/30, A61K9/12, A61K8/34C, A61K8/67, A61K8/04F, A61Q19/00, A61K8/42, A61Q17/00|