CA1095410A - Sprayable germicidal foam compositions - Google Patents

Abstract

ABSTRACT OF INVENTION
A sprayable germicidal foam composition containing a therapeutically sufficient quantity of the microbicidally active agent; an aliphatic fatty alcohol and an aliphatic fatty acid, each agent being in critical ratio to each other, in parts by weight of from 1:2 with a preferred range for this critical ratio of from 0.5 parts to 2.0 parts by weight of the fatty alcohol, to 1 to 3 parts by weight of the fatty acid; a nonionic surface tension reducing agent in concen-tration of at least equal to one-half of the combined weight of the fatty alcohol and fatty acid moieties but not greater than three times the weight of the fattyalcohol present; and aqueous-aliphatic glycol mixture, in critical proportion offrom 1 part aliphatic glycol to 15 parts of water, with a preferred range of critical ratio of from 0.5 to 1.5 parts by weight of said glycol, to 7.5 parts to 30 parts by weight of water, and a suitable aerosol propellant, in sufficient quantity to provide a ratio of from 0.5 parts to 3 parts by weight of said pro-pellant to 7 to 9.5 parts by weight of sprayable composition, the whole being packaged in a pressurized container fitted with a release valve. When the con-tainer pressure is released, a durable foam is extruded to provide a safe and effective, pain-free, germicidal barrier to burned, abraded or wounded skin and mucous membranes of humans and animals, when applied form 1 to 6 times daily.

Description

lO~S-llo ll 1 This invention relates to novel sprayable germicidal compositions which

2 ¦ may be applied as a foam directly to an injured tissue surface to provide a du-

3 ¦ rable semi-permeable germicidal protective barrier to skin and mucous mem-

4 ¦ branes in a manner which is essentially pain-free. A particularly desirable

5 ¦ feature of the new compositions is that these may be adapted for convenient

6 ! dispensing from pressurized containers so that the formed germicidal foam

7 ~ may be applied directly to a wounded, abraded, burned or injured t1ssue sur-

8 face with minimum tissue manipulation and tissue injury`.

9 In particular, the present invention relates to sprayable compositions

10 comprising an active germicidal agent selected from the group consisting of

11 silver sulfadia3ine and silver sulfaphenazole; antibiotic compounds and their

12 ¦ salts; iodophor substances including povidone-iodine; and complexes of elemen

13 tal iodine with detergents; a silicone compound, as for example, dimethylpoly-

14 l siloxane; a nonionic surface active agent; a fatty alcohol and a fatty acid and

15 1 an a9ueous glycol solvent to provide a stable foam matrix, the whole being

16 packaged in a pressurized container with gas aerosol propellant.

17 When the germicidal composition i9 applied to the injured tissue surface,

18 the resultant foam possesses especially desirable long-lasting and durable 9 properties of a kind which were previously unobtainable with pressurized foam known in the art. The lasting, durable properties of the formed foam, toget-21 her with its uniform micropore character, provide a desirable semi-permeabl 22 germicidal barrier to wounded tissue surfaces to inhibit infection and at the 23 same time avoid tissue maceration by allowing vapor interchange. Further-24 more, the excruciating pain which is ordinarily encountered when germicidal preparations, as are presently used, are applied to the skin of the patient in 26 the treatment and prevention of infection of burned, wounded, or injured skin, 27 l is now eliminatcd when the new sprayable germicide-containing Compositions 28 1 are used.

~095410 Skin which has been burned, abraded, wounded or otherwise injured is 2 extremely vulnerable to infection so that it becomes necessary to provide a ger 3 micidal barrier to avoid infection which, in the presence of extensive tissue in-4 jury, may result in death. It has been recognized that infection is one of the S rI~a jor factors to complicate the treatment in the severely burned patient, and 6 thc therapcutic need to degerm burned, wounded or abraded skin is essential 7 to recovery.
8 The entire gamut of microbicidal agents have been used to degerm in-9 jured skin and mucous membranes. While it is generally acknowledged that 10 iodine is perhaps the best germicidal agent, in view of its broad microbicidal 11 spectrum, and that the newer organic iodine derivatives known as iodophors, 12 provide a substantial benefit in reducing the noxious, toxic properties of iodine, 13 there still remain many inherent limitations to the use of elemental iodine pro-14 ducts in the treatment of the seriously burned patient and the patient with se-15 verely abraded, wounded skin and mucous membranes.
16 The attempt to utilize the metal salts of the sulfa drugs also failed be-? cause of the inherent allergic reactions known for this class of antiseptic medi-18 ~ations, when these are used topically, and also because of the added toxic ef-1g ¦fects of the silver ion when the silver salts of the sulfa drugs, such as silver 20 ¦sulfadiazine are used. These agents not only do not relieve patient morbi~lity 21 ¦but they also increase the number Of toxic reactions and serious side effects 22 ¦ reported for these agents, The silver salts Of the sulfa drugs such as silver 23 ¦sulfadiazene and silver sulfaphenazole also present the further limitation to 24 ¦their use,in the well known reaction between silver iOllS and halide ions such as 25 j are found in all physiologic exudates. These chemical reactions not only de-26 ¦stroys the ionic balance Of the injured tissue surface but also poisons the tissue 27 ¦cell through the combination of the cellular proteins with the silver ion. Simi-28 ¦larly, the salts of the antibiotics provide either an acid pH or an al!caline pH
29 Iwhich leads to inherent problems of pain and tissue irritation, as well as vari-30 able drug activity bccausc oL neutralizing properticS exerted byphySiologic fluid.
I

~ . I
~0954~0 ¦ Another problem limiting the degerming of injured skin arises from the 2 ~ature of the pharmaceutical compositions used to carry the germicidal active 3 1ingredient and the methods for their use. A common method to obtain a topical 4 ¦degerming action is to apply an antiseptic ointment,or solution,to the injured 5 Isurface of such thickness as to provide a germicidal barrier over the entire 6 ~wounded area. However, the mechanical spreading of such germicidal oint-7 ¦ments and/or solutions causes such severe pain that in many instances admin-8 ¦istration of anesthetics and narcotics are required. Since the application of 9 ¦the presently utilized germicidal agents must be repeated many times during 0 ¦the day, and because these compositions lack sustaining power and are subject 11 Ito being washed away by physiologic exudates, the noxious effects caused by 12 1the pain and consequent analgesic, anesthetic and narcotic medications pose a u ¦serious threat to the patient~s life, as well as to greatly increase morbidity.
14 ¦ Still another limitation inherent to the compositions used to degerm se-15 ¦ vere~y injured, burned or abraded skin surfaces is their inability to provide for 16 ¦vapor exchange in order to avoid maceration of the wounded skin surface. Thu , 17 ¦ the spreading of a thick ointment over the injured area Inay effectively exclude 18 ¦air-borne contaminents but it also prevents the exchange of essential gases and

19 ¦moisture vapor necessary to the healing process. Moreover, the exclusion of

20 ¦ air provides anaerobic pockets which serve as incubators for foci of infectior,

21 ¦ When solutions are applied to the slcin, these are rapidly washed away by the

22 ¦tissue exudates and transudates.

23 ¦ In view of the inherent limitations known for microbicidal compositions

24 ¦presently used to degerm burned, wounded or injur~d skin, the ideal antimicro 2s ¦bicide composition to be used for the purpose should possess the following pro-26 ¦ perties:
27 ¦ (a) Be essentially pain-free upon application to the injured tissue 28 1 even when rcpeated, multiplc therapeutic procedures are re-29 quired each day.

3~ ~ (b) Provide an effective germicidal barrier anc~ w]1ich would permlt ~ 4 an exchange of the moisture and gases thereby avoiding 2 ` tissue maceration.
3 (c) That the germicidal compositions have a sustained, lasting 4 capacity when applied to abraded and/or burned skin and not be washed away by tissue exudates.
6 (d) That the germicidal compositions be conveniently and 7 easily applied to the injured skin surface.
8 (e) That the germicidal compositions be pharmaceutically 9 stable~ have reproducible and homogenous characteris-tics as well as to be microbicidally effective.
Il (f) That the germicidal compositions be safe for use on hu-It mans and animals.
13 Sprayable compositions have been proposed in the art as a mean9 of14 overcoming certain Of the limit~tions Of the compositions and methods used to15 degerm burned, injured and abraded tissues, but the formulations proposed for16 such use as a topic21 spray have failed to achieve their desired goals and in17 fact have added new problems. Thus for exalnple, the pain of application of the 18 spray compc.sitions ~as not eliminated and spray formulations to degerm injure 19 skin contain local anesthetics. (See for example, U. S. Patent 2, 782, 975 and 20 U. S. Patent 2, 801, 201).
21 Both solutions and ointments have been utilized as sprayable composi-2t tions but these failed to overcome the problem of porosity for gaseous inter-23 change and also gave rise to pockets which acted to incubate microorganism.
24 Furthermore, when hydrophilic compositions, either as an ointment or a solu:

25 tion, were utilized these were rapidly washed away and did not provide any last~ .

26 ing adherent to the injured skin surface. When hydrophobic compositions were

27 utilizcd, as for example, mineral oil preparations, thcy unevenly coated the t8 ~vet abraded skin surface and again resulted in pockets which served as foci Of t9 infection by incubating microorganisms. Thus we find the goal of providing an30 ~ c s s ially pain - f l o c ~ c I In icidi~ I icr wllicl~ pos s cs 3 c s s us talncd 1~ s ti~t ~_ I

10954iO

adherent capacity still remains to be achieved with the prior art sprayable 2 composition,~ .
It was unexpectedly found that the application to burned, abraded or 4 wounded slcin and mucous membranes of a sprayable composition containing:
a) a therapeutically sufficient quantity of a microbicidally active 6 a gent, 7 b) an aliphatic fatty alcohol and an aliphatic fatty acid, each 8 agent being in critical ratio to each other, in parts by weight 1~ op7~/m~vt7 9 of ~1:2~with a preferred range for this critical ratio of lo from 0. 5 parts to 2. 0 parts by ~.veight of the fatty alcohol, 11 ~ to 1 to 3 parts by weight of the fatty acid, 12 c) a nonionic surface tension reducing agent in concentration of 13 at least equal to one-half of the combined weight of the fatty 14 alcohol and fatty acid moi.eties but not greater than three tirrles the weight of the fatty alcohol present, 16 d) an aqueous aliphatic glycol mixture in critical proportion of ~f/~c~
17 of from 1 part aliphatic glycol to 15 parts of wate,~, with a 18 preferred range in critical ratio of from 0. 5 to 1. 5 parts by 19 weight of said glycol, to 7. 5 parts to 30 parts by weight of water, 21 e) a suitable aerosol propellant, in sufficient quantity to pro'-~ ferr~l .
~2 vide a"~ratio of from 0. 5 parts to 3 parts by weight of said 23 propellant to 7 to 9. 5 parts by weight of sprayable compo-24 s ition, 25 the whole being packaged in a pressurized container, resulted in a du..able foam 26 which possessed all of the properties of the ideal agent described above to pro-27 vide a safe and effective pain-free, germicidal barricr to burned, abraded or

28 wounded skin and mucous membranes. Upon release oI the pressure, the com-

29 position is delivered from the container to the burned~ abraded or injured skin

30 or mucous membranc s-1rIacc iJI tl~e Iorm of a foam whicll pOSsesses dcsirable f, 10954~L0 lasting qualities, and a uniform and reproducible micropore matrix which per-2 mits a gaseous exchange while providing an effective germicidal barrier to the 3 tissue surface. The active germicidal agent is fully available from the topical 4 ¦ foam to the injured tissue and the release rate of active ingredient is such as t ¦ avoid a rapid flooding of the area. The foam retains its structure on the expos 6 ed tissue surface for periods up to 9 hours after application.
7 It was further unexpectedly found that the inclusion of from 0. l parts by 8 weight to 5 parts by weight of a pharmaceutically acceptable silicone compound, 9 as for example, dimethylpolysiloxane, dimethylsiloxane ~and methylsiloxane, to ¦ the above described composition prevented the coalescence of the micropore 11 matrix, with the consequent modification in foam properties, when pH active 12 germicides are used. Thus, agents capable of shifting the hydrogen i~n poten-13 tial of the composition, which in turn affect the properties of the formed foam 14 will require the silicone stabilizer to prevent foam-coalescence and thereby re duce vapor exchange on the moist skin.
16 The ease of application of the foam avoids tissue irritation and pain.
17 1 However, it is important to recognize that the pain-free characteristics of the 18 ¦ herein described sprayable compositions are not due to its being a foam or to 19 ¦ the ease of its application since side-by-side comparison testing of the presPnt ¦ germicidal foams with those known in the art reveals that other foam formu-21 ¦ lations utilizing the same ingredients do cause pain upon application to injured 22 ¦ skin, in contrast to the present sprayable compositions. The preparations de-23 scribed herein are stable and homogenous with reproducible physical and phar 24 maceutical properties as well as being safe and effective for use in degerming the tissue of humans and animals.
26 In order to achieve effective degerming, it is preferred to use a broad 27 spectrum antimicrobial agent. While it is generally recognized that elementa 28 ¦ iodine is perhaps the most effec~ gerrnicidal agent, its corrOsive~ tissue ir 29 ¦ ritating properties have restricted its usage to degerm wounded tissue. I~ow-~ ever, thc newer iodinc derivativcs such as the members of the class known as

31 ~ iodophor COmpOUtl(lS l~avc C]imitlatCCI many of tllC lloxiOUs limi~,atinS Ol ClemCI~

32 1I tal iodine, ~llilc r ctaini)-lg its dCsiral~lc l)rad Spcctrum a"~;"liclobial pl opcrlitS
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... . .. . .. . .

109S4~0 The preferred iodophor compound of the class of iodophor compounds re-2 mains its first discovered metmber, povidone-iodine, which is marketed under . . ~r~
¦ 3 the trade ~e of BETADINE and has been extensively scientifically studied ¦ since its inclusion i,n U. S. Patent Z, 739, 922. It is important to recognize that S ¦the class of organic iodophor compounds consist of essentially two different 6 ¦ types of iodine derivatives; those formed as a loose mixture complex of elemen .
7 1 tal iodine with a surface active detergent and the non-detergent organic iodine 8 1 compound. Povidone-iodine is the only known non-detergent iodophor compounc 9 ~ established to be safe and effective for use in humans and animals and consists ¦ of the complex compound formed from elemental iodine and povidone. The othe ll organic chemical members of the general class of iodophor compounds, consis 12 of a loosely-bound complex of iodine with a detergent surface active agent, as 13 for example, such surface-active detergents as nonylphenoxypoly(ethyleneoxy)-14 ethanol, polyoxypropy]enepolyoxyethanol, sodium N-coco-N methyltaurate, co-15 conut oil-fatty amides, and undecoylium chloride, to form the corresponding 6 iodine iodophor complexes. When a member of the class of iodophor germicida l 17 ¦agents described above is desired for use as the active degerming agentthen 18 the concentration of the particular iodophor compound selected is from 1 to lS
19 percent by weight of the weight of the composition.
20 l Antibiotic substances may also be utilized as a degerming active ingredi-21 ¦ ent in the present composition and the entire range o antibiotic compounds as 22 is used in topical anti-inective therapy may be included in the new composition .
23 Examples of the separate classes of antibiotics which are useful as germicidal t4 active ingredients in the present compositions include:
zs I (a) Aminoglycosides which are characterized in that they contain 26 one or more amino-sugars, such as glucosamine or neosa_ 28 minc, and are linked by glucoside linkagcs to a basic 6-membcred ~albon rinr, at for e:~ample, streptidille or _.
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~095410 ¦ strephine. Examples of such antibiotics are gentam~ycin, 2 ¦ kanamycin sulfate, s~:reptomycin sulfate and other salts, 3 ¦ neomycin sulfate and neomycin undecylenate.
4 ¦ (b) The cephalosporins, characterized by the cephalo-¦ sporanic acid moiety include such agents as cephalexin, 6 ¦ cephaloglycin, cephaloridins, cephalothin sodium cefa-7 ¦ zolin sodium and cephapirin sodium.
8 ¦ (c) The macrolides are a special group of antibiotic com-9 ¦ pounds containing a macrocylic lactone moiety contain-lo ¦ ing 12 or more carbon atoms in the primary ring. Macro-Il ¦ lides useful as active germicidal agents in the present 12 ¦ compositions include such agents as erthromycin, l3 ¦ nystatin, rifampin, amphotericin-B, mitasamycin, 14 ¦ oleandomycin, spromycin, proleandomycin and their 15 ¦ salts and mixtures of the same.
16 (d) Penicillin antibiotics which are natural products obtained 17 by culturing Pencillium species, and now also includes 18 synthetic antibiotic compounds which are 6--f;-carboxy-19 amino derivatives, include such agents as ampicillin, penicillin G and its salts, carbenicillin disodium, di-21 cloxacillin sodium, methicillin sodium, nafcillin sodium 22 oxacillin sodium and phenethicillin potassium.
23 (e) The tetracycline antibiotics include tetracycline and 24 its salts, chlortetracycline hydrochlide, demecly-cline and its acid, salts, doxycycline and its salts, 26 methacycline hydrochloride, minacycline hydrochloride, 27 oxytetracycline and its salts.
28 (f) Miscellaneous antibiotic substances include bacitracin 29 and its metal salts, colistin, capreomycin sulfate, .
gramici<lin, and Polymyxin B sulfate.

9 _ . .~

The range in concentration for the antibiotic substances used in the 2 ¦ subject compositions will vary with the particular compound and ranges from 3 ~ 0. 1% by weight to 15% by weight, of the weight of the compositions. The exact 4 ¦ concentration of the selected antibiotic agent to be incorporated in the compo-sition will vary with the patient's needs, as well as the germicidal potency and6 sensitivity of the organisms being treated.
7 ~ Those members of the class of p-aminobenzene sulfonamide derivatives B which are known as sulfa drugs and are useful dermatologic therapy have a9 special use in the degerming burned skin. In particular such sulfa drugs as silver sulfacetamide, silver sulfadiazine, silver sulfaphenazole, and sulfa-11 ¦ mylon are preferred compounds of this class to be incorporated in the present 12 1 compositions. When the sulfa drugs are used to degerm the skin the usual 13 concentration in the composition is between 0. 5 and 5% of the weight of the 14 composition.
Other antimicrobial agents useful to provide a degerming action in the 16 1 present composijtions include silver nitrate, silver proteinate, the nitrofurane 17 ¦ compounds, hexachlorophene, gentian violet and the quaternary ammonium 18 j germicides which includes alkylbenzyldimethyl amino salts.
19 ¦ When the germicidal compositions are used to disinfect, treat or de-¦ germ wounded, abraded or burned skin, these are applied topically as a forme~
21 foam which involves a three-phase system.
22 (a) The foam matrix which comprises a hydrogen-bonded complex 23 of an aliphatic fatty alcohol of the formula ROH wherein R is 24 an unsaturated and/or saturated hydrocarbon chain consisting 25 1 of from 10 to 18 carbon atoms in chain length, hydrogen-26 bonded with a saturated and/or unsaturated aliphatic fatty 27 acid of the formula R- COOH wherein R is from ld~ to 18 28 carbon atoms in chain length;

1, -10- ' ~
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(b) a s olution and/ ~r s uspeD s ion of a th-rapeutically a cti~e ingredient in a specially formulated aqueous solution having 3 ¦ a dielectric ~onstant at strength to support the formed hy-4 ~ drogen-bond between the fatty alcohol and the fatty acid, and 6 I (c) an immiscible liquid aerosol propellant having an interfacial 7 ¦ tension of less than 2 dynes/cmZ at the interface of the liquid 8 ¦ aqueous solvent.
9 ¦ It is essential to recognize thc interrelationship of the separate phases 10 ¦ to the unexpected new and novel properties of the new hydrogen-bonded foams 11 ¦which distinguish these compositions from the foam compositions of the prior 12 ¦ art. The hydrogen-bonded foam matrix provides a micellular structure to the 13 ¦ formed foam which engulfs the liquid germicidal composition, at the same time 14 providing a rigidity to the foam. Water, a strongly polar solvent, has the de-15 sirable dielectric constant to form a hydrogen-bonded complex through a sol-16 1 vation reaction but it also has certain inherent physical-chemical limitations 17 ¦ for use in foam formulations. It becomes necessary therefore to formulate 18 ¦ the aqueous solvent to overcome the physical limitations of water at the same 19 ¦ time that the dielectric constant of the solvent is preserved at a strength to 20 ¦ support the formation of a hydrogen-bonded complex through a solvation re-Zl action. The interfacial tension limit of less than Z dynes/cm2 between the im-22 miscible liquid aerosol propellant and the germicidal composition, is essential 23 ¦ to form a uniform micropore character to the foam so that the micelle porosit 24 ¦ is less than 40 microns in diameter, and thereby provide for optimal release r~
25 ¦ of active ingredient to the skin surface as well as to enable the exchange of 26 ¦ gaseous vapors to prevent maceratioll of the covered tissues.
27 l It was unexpectedly found that when the amounts of the components mak-28 ¦ ing up the separatc phases ~vere altered so that these amOuntS exceeded the 29 ¦ quantities set forth abovc, that the ormcd foam did not h~vc the desirablé
30 ! properties of the new ~oam compositions. ~urthermorC. ~vhen the ratio of tllc ll separate phases to each other was altered rom those set forth above, that the 2 formed foam did not have the` desirable physical properties determined for the 3 nevl foams and also did not release the active ingredient at the desired rate.
4 It is the special characteristics of the novel three-phase foam composition that distinguish the subject foams from those of the prior art, 6 It is known that polar solvents are made up of strong dipolar molecules, 7 have marked hydrogen-bonding properties and react vith dissociated chemical 8 compounds. The interreaction between a solvent and a dissociable chemical 9 compound is termed, solvation, and involves the orientation of the solvent molecules about the ormed ions and/or charged particles of the solute. Such 11 orientation however only occurs when the dipoles of the solvent are directed to 12 and complexed with the charged particles or ions of the solute through hydro-13 gen-bonding. A polar solvent that enters into and forms a solvated hydrogen-4 bonded complex must possess the ability to keep the solvate-charged particles apart with minimunl energy expenditure and this property is reflected in the 16 dielectric constant for the solvent.
17 l Chemicals having a strong tendency to dissociate and form hydrogen-18 1 bonded complexes are not as readily fragmented or dissociated by strong polar 19 ¦ solvents than are compounds having a lesser tendency to form hydrogen bonds.
20 l It is recogni~ed that water is a strongly polar solvent with a dielectric constan 21 ¦ of 78. 5, a molar dipolari~ation of 17. 4 and dipole moment of 1. 85, and there-22 ¦ fore enters into solvation reactions to form strong hydrogen-bonded complcxes 23 ¦ While water has highly desirable electricalproperties as a polar solventfor 24 general use in foams, its use as a solvent wherein a hydrogen-bonded matrix 25 1 is formed between two hydrophobic moieties, as for example a fatty alcohol 26 and a fatty acid, presents certain problems si!nce complex formation would be 27 interferred with by the strong solvation reaction characteristic of water. More 2~ over, its use in forn~ulations of rmedicament foams has several other in~lerent 29 limitations which necessitate the necd to modify thc properties of water as a ~ solvent in a oan~ formulation.

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The high vapor pressure, volatility and high evaporation index of water 2 provides a foam of limited durability. When such aqueous foams are exposed 3 to the atmosphere any solvation-reaction, hydrogen-bonded complex as may 4 I be formed are destroyed and the foam rapidly collapses. This foam matrix 5 ~ collapse would result in the formation of a water and vapor resistant barrier 6 1 over denuded skin which would not permit the interchange of gases and vapor.7 ¦ Since the continuous external phase of the foam matrix is hydrophobic, 10 then th :rele~se Clf active ing ed~ent contained In the enclc~sed aqueous fluid 11, 13_ ll !

1 ~09S4~0 solvent is impeded and therapeutic efficacy is hindered. The overall volatility 2 and high vapor pressure of the aqueous solvent, together with the solvated col-3 lapse of the foam matrix, causes rapid drying after topical application of the 4 foam,together with less-than-satisfactory release of the active ingredient.
5It was unexpectedly found that when a critical quantity of a semi-polar, 6 non-volatile, humectant solvent is added to the strongly polar solvent, water,7 that there is a modification in the overall di-electric properties of the solvent-8 mixture which results in a reduced di-electric constant for the solvent-mixtur~ , 9 which does not destroy the hydrogen-bonded formed foam matrix through sol-10 vation. This reduced di-electric constant for the solvent-mixture now support Il the hydrogen-bonding o the formed foam matrix to stabili~;e the complex form-12 ed between the fatty-alcohol - fatty-acid which results in new and unexpected t3lasting properties of the foam; an increase in gas and vapor exchange of the .
14 foam,as well as a highly desirable release of the active ingredient from the 15 foam to the skin and mucous membrane surface. Since the process of dissoci-16 ation is a basic step in the hydrogen-bonding process and involves separation l? of cations and anions followed by an orientation of the molecules of the solvent 18 about the charged iO115, the di-electric strcngth and type of polarity of the sol-19 vent becomes the important determinant to its capacity to support a formed 20 covalent hydrogen bond. A-s electrical solvation forces of the solvent decrease 21 the more lasting becomes the formed complex between a hydrophobic fatty al-2t cohol and a hydrophob-c fatty acid, which constitute the foam matrix.
23Propylene glycol, glycerinc and a poloxyethylene glycol compound hav-24ing a molecular ~veight of from ~00 to 800, are utili~ed as semi-polar solvents 25 to modify the electrical properties of the polar water solvent. These semi-26 polar solvents, i. e., propylene glycol, glycerine and polyoXyethyleneglycol, 27 are strong dipolar molecules, but they do not enter into solvation reactions to 28 form solvatcd hyclrogen bonds and thercby decrease the solvation capacity of 29 a mixed solvcnt. .he modification of the strongly polar electrical prOpcrtics 30 o~ ~vater by propylene glycol, glycerine and the polyoxyctllylelleglycol not only Il I

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0~541(~

contributes materially to the strength of the fatty alcohol-fatty acid formed matrix, but also conveys humectant, nonvolatile properties to maintain a polar-semi-polar fluid balance which controls overall foam stability, gas and vapor interchange as well as the release of active ingredient, all of which are re-flected in the improved highly desirable therapeutic activity of these foams.
It was further unexpectedly found that the proportion of fatty acid to fatty alcohol was critical to the formation of the hydrogen-bonded complex of the foam matrix and that the proportion of this formed complex to the volume of polar solvent was also important, as was the proportion of semi-polar solvent to polar solvent in establishing a desirable electrical balance for the solvent.The critical ratio of fatty alcohol to fatty acid was found to be one part fattyalcohol to two parts fatty acid optimum, with a preferred range being from 0.5 to 1.5 parts by weight of fatty alcohol to 1.0 to 3.0 parts by weight of fatty acid. The critical ratio of the semi-polar solvent to polar solvent was found to be 1:15 optimum, with a preferred range of from 0.5 to 2.0 parts by volume ofsemi-polar solvent for each 7.5 parts to 30 parts by volume of water, as the *
strongly polar solvent. The optimum ratio of the combined fatty acid-fatty alcohol component to semi-polar solvent is 1:27, with a preferred range in such ratio of from 1.5 to 4.5 parts by weight of combined fatty alcohol-fatty acid component to 45.0 parts by weight of solvent.
When the above-described compositions are mixed with one part of a suitable aerosol gas propellant for each nine parts of composition and the whole packagedin a pressurized container fitted with a release valve, a highly desirable ger-micidal foam is formed when the pressure is released. This foam possesses superior lasting properties and is capable of providing a desirable germicidal topical coating to skin and mucous membranes. It is necessary to achieve a uniform dispersion or solution of the aerosol gas propellant in the fluid compo-sition to produce a uniform porosity within the formed foam in order to permit satisfactory gaseous interchange while providing a germicidal barrier. It was found that when a nonionic surface tension reducing agent is present in r ~

~0~5410 ¦ critical concentration of from 1 to 3 parts by weight, said amount being at 2 1 least equal to one-half the combined weight of the fatty alcohol - fatty acid 3 ~ matrix, there was a lowering of the interfacial tension between the fluid germ-4 ¦ icidal concentrate and the gas propellant, to less than 2 dynes/cmZ and thereby 5 ¦ causing a uniform microporosity to the formed foam.
6 ¦ A nonionic surface tension reducing agent selected from the known 7 1 groups of nonionic surface tension reducing agents and/or mixtures of these 8 ¦ may be used to reduce the interfacial tension between the liquified propellant 9 ¦ phase and the fluid phase to provide a uniform distribution of phases to result lo ¦ in a fine micropore character to the formed foam and such nonionic surface ll tension reducing agents may be advantageously used:
12 (a) the poly(oxyethylene)-poly(oxypropylene)-polyethylene 3 polyol compounds, known in the trade as Pluronic Polyols 14 and are marketed by the BASF Wyandotte Corporation and which are described in U. S. Patent 2, 674, 619, 16 (b) the octylphenoxypoly-(ethylenoxy)-ethanol compounds, 17 known in the trade as Igepal CA compounds and are marketed by GAF Corporation, New York City, l9 (c) the fatty acid-polyoxyalkyl esters of hexahydric alco-hols known in the trade as Spans and Tweens and which 2l are described in the Carolina Journal of Pharmacy, 22 Vol. 33, p. 465, (1952) and the Merck Index, 8th ~dition, 23 P- 973.
24 Furthermore, the lowered surface tension of the aqueous phase and the 25 reduced interfacial tension to below 2 dynes/cm2 between the liquid propellant 26 and fluid phase serves to provide a ~niform distribution of the liquified gas 27 propellant within fluid iipophilic a1ld hydrophilic p~ases to result in a uniform 28 microporc charactcr to t1le formed foam. This micropore foaln ser~eS to en-29 hance the release of gernlicidal agent and exchange of gaseouS vapors to mate-30 rially cnha1lce tllc gcrmicidal activity and ~1tility o~ the formCd foam barrier.
~Trade ~

10~5410 Any pha: maceutlcally acceptable llqul~iable ~as aerosol propellant suit-2 , able to prepare pharmaceutical foams may be used as the propellant for the 3 ¦present compositions. Such liquid aerosol propellants as the fluorinated hy-4 drocarbons, the 1uorochlorinated hydrocarbons, hydrocarbons and inert gases 5 are pref~rred propellants. The halogenated hydrocarbons are primarily de-6 rived from methane, ethane and cyclobutane and are prepared by replacing one 7 or more of the hydrogen atoms of these compounds with one or more chlorine 8 and/or fluorine atoms. The fluorinated and/or chlorinated hydrocarbons are 9 non-polar compounds that are miscible with non-polar solvents and for the 0 most part these agents are not miscible with water.
Il Among the preferred halogenated hydrocarbon propellants are trichloro-12 fluoromethane, with a boiling point of about Z4 C.; dichlorofifluoromethane, t3 with a boiling point of about -30 C.; dichlorofluoromethane, with a boiling point 14 of about 9C.; chlorodifluoromethane, with a boiling point of about 48C., and 15 dichlorotetrafluoroethane, with a boiling point of about 4C. Mixtures of the 16 ¦halogenated hydrocarbon propellants may also be used and a mixture of trich-17 ¦lorofluoromethane and dichlorodifluoromethane is particularly useful.
18 ¦ The hydrocarbon propellants are also useful in forming germicidal 19 ¦foams but their flammability limits their general use. However, mixing with 20 la fluoronated and/or chlorinated hydrocarbons and/or the inert gases such as 21 ¦ carbon dioxide and nitrogen makes it possible to reduce the flammability ha-22 zard. The hydrocarbon propellants have several special advantageous prop-23 erties which is desirable to tlle present three-phase aerosol foam system in 24 that these have a unique chemical stability, do not react with halogens and po-ssess a better solubility characteristic than the other liquified gas propellants.
26 When the selectcd aerosol propcllant is used, a prefcrrcd ratio of gas 27 propellant to composition is one part gas propcllant and ninc parts of the com-28 position and the whole packaged in a suitable pressurizecl container fitted with !
29 a suitablc relea~e valvc. ~hen tl-e container prCssure is released and the 30 formcd foam C~;tlnldCS as a higl~ly dcsir~ lc con~posi~ n to provicle a gc i , !
- ,, .. ... _ . _ . .. _ _ _ _ _ . ~ . _ .

cover to protect and degerm burned, injured and/or abraded skin and mucous 2 membranes. The formed foam has an average pore size of less than 20 microns 3 lin diameter with a range of from 5 to 40 microns in pore diameter. After one 4 hour open exposure, the foam height is 100% of its initial value with a s calculated half-life of about 5-7 hours. There is no phase separation after 6 four hours of closed exposure at room temperature.
7 A preferred composition providing effective germicidal foam cover to 8 wounded, burned and/or abraded skin is prepared by placing 75 parts by weight g of purified water in a suitable container, fitted with a stirrer and warming o device, and adding 5 parts by weight of propylene glycol; 0.3 parts by weight of nonylphenoxypolyethyleneoxyethanol and 1.7 parts by weightof poly)oxyethylene -poly(oxypropylene)-polyethylenepolyol, whiCh is known in the trade as Pluronic B3 F-68, and the whole warmed, under constant stirring until a clear solution is1; 14 obtained.
S In a separate vessel, 1 part by weight of cetyl alcohol is mixed with I6 2 parts by weight of stearic acid and the whole melted. The melt of the .cetyl alcohol-stearic acid mixture is added with vigorous stirring to the warmed I I8 aqueous-propylene glycol solution, which was earlier prepared and maintained 19 at the same temperature. The pH of the composition is adjusted to be not less than pH and not greater than pH-6 and the heat source removed. As the composi-21 tion cools, 10 parts by weight of povidone-iodine is added and the composition 22 ~ stirred until complete solution is achieved. The pH of the solution is adjusted 23 Ito be not less than pH 4.8 and not greater than pH 6Ø The finished composi-24 tion is a thiCk, amber-colored liquid, with a surface tension of less than 2s 30 dynes/cm2.
26 The composition is filled into suitable pressurized containers, and a 17 suitable liquid aerosol propellant added so that the ratio of liquid propellant 28 to composition is from 1 part b~ wei~Jilt of propellant and 9 parts by weight of 29 Icomposition, with a preferred range of from 1 part by wei9ht o-F propellant and !4 parts by weight of coml)osition, to 1 part by weight of propellant to 14 partS ¦

I * Jr~ rk - 1~3 - 1l , .

10~5410 1 ¦by weight of composition. A preferred propellant for the above described 2 ¦composition is 1 part by weight of a 1.5 to 1.0 parts by weight mixture of 3 Idichlorodifluoromethane and dichlorotetrafluoromethane, although a 9.1 parts to 4 ¦1 part mixture of isobutane and propane may also be used. The fill per ¦container is such that a vapor pressure of not more than 55 psig and not less 6 than 35 psig at 70F iS obtained.
7 I When the pressure is released, the formed foam extrudes at a uniform s ¦rate and has the following properties:
9 ¦ (a) Micropore Size and Distribution: The preferred pore-size for the formed lo ¦ foam is not less than 1 micron in diameter and not greater than 40 Il ¦ microns in diameter ~ith a preferred range in micropore distribution of:
12 I Pore Size% Range inFound - %
13 I (microns)Distribution Distribution .
I 1 - 5 0 - 10 % 8 %
14 1 5 - 10 10 - 20 % 14 %
10 - 20 45 - 60 % 53 %
~5 1 20 - 30 20 - 30 % 22 %
30 - 40 0 - 10 % 3 %
~6 ¦ (b) Foam Stabillty: After one hour of atmospheric exposure the height 8 ¦ of a two-inch foam column was unchanged but cdlapsed after 9 hours ~9 I of standing. The calculated range for the half-life of the extruded I foam is 5 to 7 hours.
I (c) Phase Reversal: The phase reversal index for a 1 gm. sample of the 2l 1 formed foam is not more than 1% after 4 hours of covered exposure at 23 I room temperature as evidenced by separation, seepage and draina9e.
24 ¦TO the above described formulation may be added suitable pharmaceutical aids 25 ¦as for example buffering agents, silicone compounds as for example, dimethyl-26 ¦polysiloxane, methylpolysiloxane and phenyldimethylpolysiloxane.
27 ¦ When this foam is applied to burned, abraded and/or injured skin of 28 ~ humans or animals, there is virtllally no pain experienced in contrast to the 29 Isevere pain and trauma caused by the use of the conventional de9erming agents.
;Repeated daily applications of up to four times per day for extended Perjods of -19- ! -Il l ~0~54~0 . .

time, did not r'eveal any tendency to tissue sensitization and/or local z ¦irritation. Effective degerming of the skin and mucous membrane is rapidly 3 achieved so that uneventful recovery with minimal neEd for skin grafting.
~ When the above described germicidal foam was used to degerm the skin s of a patient with 35% partial and full thickness burns of the face, forearms, 6 hands and both legs, there was no pain on appiication of the germicidal foam 7 and the patient was discharged after lO days of treatment without any sign of 8 topical infection or the need for skin grafting.
g In the other study of burn patients, it was found that multiple appli-o cation of the present foam resulted in rapid degerming of the skin so that there I1 was no occurrence of topical infection during the treatment period with : uneventful healing. When the foam was used to cover abraded skin resulting .
13 after industrial injuries, a rapid pain-free degerming occurred without any 14 evidence of topical infection during the treatment period. When the foam was used under a bandage there was no maceration of the skin as sometimes occurs :16 when the conventional topical preparations are used and which seal the skin.
17 The following examples illustrate the scope of the present invention 8 ¦but it is not intended to be limited thereby.
19 ¦ - _XAMPLE 1 When it is desired to prepare a germicidal foam, then, 21 Step 1. In a suitable container fitted with a stirrer and heating ~2 device, is placed 15 pounds of propylene glycol; 4.5 pounds of Poloxamer-188, 23 which is marketed as Pluronic F-68 Wyandotte Chemicals Corporation of 24 Michigan; 3 pounds of disodium phosphate; 2.2 pounds of citric acid anhydrous and 220 pounds of purified water. The mixture is stirred until complete 26 ¦ solution is achieved and then l pound of Igepal-C0-630, which is marketed by 27 ¦ General Aniline and Film Corporation, New York is added to the solution.
28 IThe solution is heated to about 70C and filtered.
29 ~ Step 2. In a separate container, 3 pounds of cetyl alcohol is melted . , . _ . , 3~ I and 6 pounds of stearic acid dissolved to this nlelt witn the aid o-f yentle I¦ ~ Ir~6le marK

!

heating. The temperature is maintained at about 65C. to 70~C. and 0.3 pound 2 of dimethylpolysiloxane is added to the melt of cetyl alcohol and stearic acid.
3 The mix is stirred while the temperature is maintained at 65C. to 70C.
4 Step 3. Add the molten cetyl alcohol, stearic acid, silicone mixture obtained as a result of Step 2, to the solution obtained as a result of Step 1 6 and stir until a homogenous dispersion results.
7 Step 4. When the dispersion cools to 30C., add 30 pounds of povidone-8 iodine powder and stir until it has been completely dissolved. The pH is g continually monitored so that it is never below pH 4.0 nor greater than pH 6.
o Step 5. Add sufficient purified water to bring the batch weight of 300 pounds and continue stirring until the temperature is that of the room 2 temperature. Allow the composition to stand overnight in a tightly-stoppered 3 container. This product is now known as the concentrate-dispersion and has a 4 surface tension of between 25 and 28 dynes/cm2 at 25C. and a pH of 5.5.
Step 6. After suitable period of standing, the concentrate-dispersion 6 is packaged in a pressurized container with a liquid aerosol propellant such as 7 isobutane and/or propane or the halogenated hydrocarbons. The ratio of 8 concentrate-dispersion to propellant is 9 parts by weight of concentrate-lg dispersion to 1 part by weight of liquid propellant. The interfacial tension 20 between the concentrate and liquid propellant is between 0.5 and 1.5 dynes/cm2 21 at 4.0C. When the liquid propellant-concentrate dispersion is filled into a 22 pressurized container, the container pressure should be not less than 35 psig 23 and not greater than 55 psig at 70F.
24 The pore size distribution of the formed foam is:
Pore SizePercent ~crons)Distribution 26 I 0 - 5 7 %
27 1 5 - 10 13 %
I lO- 20 5l %
28 20 - 30 ;~4 %
29 30 - 40 - 5%

1. i 10~$5410 The heig t of a 2 inch foam column remains unchanged after one hour exposure 2 to the atmosphere and collapsed after nine hours of standing. After four hours 3 1f standing under covered exposure at room temperature conditions, a 1 gm.
4 aliquote foam sample showed no phase reversal.
s EXAMPLE 2 6 In a suitable container fitted with a stirrer and heating device is 7 placed 10 gm. of polyethyleneglycol-400; 15 gm. of Igepal C0-630 and 150 gm.
8 of purified water. The mixture is stirred until complete solution is achieved 9 and then warmed to about 70C; a melt of 10 gm. of lauryl alcohol and o 20 gm. of linoleic acid is added under vigorous s~irring to achieve a uniform dispersion. The pH of the dispersion is adjusted to pH 5.5; cooled to room ~2 temperature and 5% by weight of silver sulfadiazine is added. The mixture is stirred to achieve a uniform distribution of the silver sulfadiazine and the whole allowed to stand overnight at room temperature. The surface tension of the concentrate is 24 dynes/cm2 at 25C. The concentrate dispersion is packaged 6 in a pressurized container fitted with a release valve utilizing a mixture of 40~ dichlorodifluoromethane and 60~ dichlorotetrafluoroethane. The interfacial 18 tension between the propellant and concentrate is 0.7 dynes. The range in 19 container pressure is not less than 35 psig and not greater than 55 psig at 20 70F. The micropore distribution of the formed foam is:
21 Pore SizePercent 2t (MicronsLDistribution 0 - 5 5 %
23 5 - 10 12 %
. 10 - 20 54 %
24 20 - 30 24 %

30 - 40 4 %

26 The pH of the formed foam is pH 5.5.

28 Stearyl alcohol, 0.5 gm. and lauric acid 1.5 gm. are mixed with 29 3 gm. of glycerine and the whole warmed to 70C. W~len solution is achieved a solution of 1 (Jm. of Plllrr)nic E-h~ dissnlve~ in ~s nl11. of ~3trr i~ ~ddcd I z~ !
I

1095~10 ¦and the mixture vigorously stirred, while temperature is maintained at 7Q C.
¦The temperature is allowed to cool to room temperature and 3% by weight of 3 lerythromycin is added. The surface tension of the concentrate is 27 dynes/cm~
4 ¦at 25C. The concentrate-dispersion is then packaged in suitable pressurized ~container using a liquified fluorinated hydrocarbons which is known in the art B as Freon and marketed by Dupont Chemical Corp. as the propellant. The inter-7 1facial tension between the propellant and concentrate is 0.8 dynes. The 8 ~resultant sprayable composition forms a desirable foam that is useful in the g ¦treatment of burned, wounded and abraded skin and which has the following ¦micro-pore distribution:
ll ¦ Pore Size Percent 12 ¦ (Microns) Distribution I 0 - 5 7 %
13 1 5 - lO 25 %
1 lO - 20 49 %
14 1 20 - 30 18 %
30 - 40 l %

6 ¦The pH of the formed foam is pH 3.2.

1S In place of the fatty alcohol described in Examples l through 3 above, 19 there may be substituted in equal parts by weight a saturated or unsaturated 20 fatty alcohol selected from the group consisting of decyl alcohol, dodecyl 21 alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, 22 oleyl alcohol, linoleyl alcohol and mixtures of these. The ratio of the 23 fatty alcohol to the fatty acids as used in Examples l through 3 above and 24 Example S below is l:2, with a preferred range of from 0.5 to l.5 parts by 2s weight of fatty alcohol to l:3 parts by weight of fatty acid. The remainder 26 of the steps being the same and the formed foam is useful to de9erm burned, 27 abraded or injured skin and mucous membranes.

29 In place of the fatty acid set forth in Examples l through 3 above, there~
Imay be substituted in equal parts l)y wei(Jht a f~tty 3cid select~d fr~ the ~ro~lp r~e ~arK
-Z3~

1095~10 ¦ consisting of lauric acid, myristic acid, stearic acid, linolenic acid, 2 ¦ linoleic acid, oleic acid and mixtures of these. The remainder of the steps¦ being the same and the formed foam resulting is useful to degerm burned, 4 ¦ abraded or injured skin and mucous membranes.
¦ EXAMPLE 6 6 ¦ In place of the nonionic surface tension reducing agent described in 7 IExamples l through 5 above there may be substitutèd in equal parts by weight 8 ¦ of a nonionic surface tension reducing agent selected from the group consisting 9 lof the poly(oxyethylene)-poly(oxypropylene)-polyethylene polyol compounds, B Iknown in the trade as Pluronic Polyols; the octylphenoxypoly-(etheneoxy)-11 ¦ethanon compounds, known in the trade as Igepal CA compoundsi the fatty-acid-12 ¦polyoxyalkyli esters of hexahydric alcohols, known in the trade as Spans and13 ¦Tweens, and mixtures of these. The preferred concentration of the nonionic 14 ¦surface tension reducing agent is at least equal in parts by weight to one-half ¦of the combined weight of the fatty alcohol and fatty acid moieties but not 16 Igreater than three times the weight of the fatty alcohol present. The 17 ¦remainder of the steps being the same and the formed foam is useful to degerm 18 ¦burned, abraded, or injured skin and mucous membranes.
19 ¦ EXAMPLE 7 20 ¦ In place of the aliphatic glycol used in Examples l through 3 above,21 Ithere may be substituted in equal parts by weight of liquid glycol compound 22 ¦selected from the group consisting ôf polyoxyethylene glycols having a 23 Imolecular weight of from 200 to 800, propylene glycol, glycerin and mixtures 24 ¦ of these. The ratio of the selected glycol compound to the amount of water25 present in the finished formulation is l part by weight of selected glycol to26 l5 parts by weight of water with a preferred range of from 0.5 to l.5 parts by 27 weight of the selected glycol comnound to 7.5 to 30 partS by weight of water,28 the remainder of the steps being the same and the formed foam resulting is use- ¦
29 ful to degerm bu~ned, abraded, or injured skin and mUcuS Inembrane5.

I -2~-. .
¦ EXAMPLE 8 2 ¦ In place of the dimethylpolysiloxane used in Example 1 above, there 3 ¦may be substituted in equal parts by weight another pharmaceutically 4 Iacceptable silicone compound as for example, methylpolysiloxane and 5 ¦phenyldimethylpolysiloxane. The preferred range of concentration of the 6 ¦selected silicone compound is from 0.05% to 1.0% by weight.
7 ¦ The silicone compound as set forth above may also be included in the 8 ¦foam formulation set forth in Examples 2 through 7 above and is used in a 9 ¦preferred range in concentration of from 0.05% to 1.0% by weight.
o EXAMPLE 9 l1 When it is desired to demonstrate the release of the active germicidal lt agent from the formed foan, then trypticase soy agar plates are innoculated 13 with a test microorganism as for example, staphylococcus aureus, ATCC6538;
14 escherichia coli, ATCC 11229; proteus vulyaris, ATCC 13315;
streptococcus fecalis, ATCC 8043; pseudomonas seruginosa, ATCC 104145;
16 aerobacter aerogenes, ATCC 13048; streptococcus pyogenes. Approximately 0.5 17 gram of the formed foam as for example the formed foam obtained as a result 18 of Examples 1 through 7 above, is placed on thP surface of each innoculated 19 plate and the plates are then incubated at 37C. for seven days and the 70rie 20 of inhibition measured. Representative results of this test with the formed 2~ foam, obtained as a result of Examples 1, 2 and 3 above are:
22 Zone of Inhibition of Microbicidal Growth w th a Foam,_Obtained as a Resu t of:
23 TEST QRGANISM Example 1 _ample 2 Example 3 24 Staphylococcus aureus, ATCC 6538 27 mm. 19 mm18 mm.
Escherichia coli, ATCC 11229 26 mm. 21 mm.16 mm.
26 Proteus vulgaris, ATCC 13315 25 mm. 20 mm.12 mm.
27 Streptococcus fecalis, ATCC 8043 27 mm. 21 mm.19 mm.
28 Pseudonlonas seruginosa, ATCC 104145 24 mm. 22 mm.17 mm.
29 Aerobacter aerogenes, ATCC 13048 28 mm. 19 mm.14 mm.
Strel)tococcus pyogenes 22 nlm. 19 mn. 17 mm.
~, i .~ s 109~410 1 EXAMPLE lO
When it is desired to degerm burned skin of humans and animals, then 3 the foam formed as a result of Examples l through 8 above is applied to the 4 injured tissue and/or mucous membranes from l to 6 times daily. A foam layer s of at least one-half inch in height is applied to the injured area which may be 6 covered or left uncovered, depending upon the particular patient's need.
7 he film surface formed by the foam over the injured skin serves to provide s a microbicidal barrier at the same time permitting a gaseous interchange to-g avoid maceration. The treated burn sites heal rapidly so that minimal skin o grafting was required. A notable effect is the absence of pain during-and-after application of the germicidal foam to the injured area.
12 In a similar manner, abraded and wounded skin and mucous membranes 13 may be degermed through the application of the germicidal foam from l to 6 ts ~ times dai .

26 i `

_~o_ .. .. . . _, . . . . _ , .

Claims (20)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A sprayable pharmaceutical composition of pH not greater than 6, for topical application to the injured skin of humans and animals, comprising:
(a) an aliphatic fatty alcohol of the formula ROH, wherein R is a saturated or unsaturated alkyl group of from 10 to 18 carbon atoms in chain length, and mixtures of these;
(b) an aliphatic fatty acid of the formula RCOOH, wherein R is a saturated or unsaturated alkyl group of from 14 to 18 carbon atoms in chain length and mixtures of these, the concentration of said fatty acid being from 1 to 3 parts by weight of fatty acid for about 0.5-2 parts by weight of fatty alcohol;
(c) a nonionic surface tension reducing agent selected from the group consisting of poly(oxyethylene)-poly(oxypropylene)polyethylene polyol compounds, the octylphenoxypoly(ethyleneoxy)ethanol compounds, the fatty acid polyoxyalkyl esters of hexahydric alcohols, and mixtures of these, the concentration of said non-ionic surface tension reducing agent being at least equal to one-half the combined weight of the fatty alcohol and fatty acid moieties, but not greater than three times the weight of the fatty alcohol present;
(d) an aqueous-aliphatic glycol mixture, said glycol selected from the group consisting of polyoxyethylene glycol, having a molecular weight of from 200 to 800, propylene glycol, glycerin, and mixtures of these in critical proportion of from 0.5 to 2.0 parts by weight of said glycol to 7.5 to 30 parts by weight of water;

(e) a therapeutically sufficient quantity of a microbicidal agent;
(f) a suitable aerosol propellant which is gaseous at normal pressure and liquid at increased pressure;
the whole being packaged in a suitable pressurized container fitted with a release valve, so that upon release of pressure the composition is released in the form of a stable foam for application to the injured skin.

2. The composition of claim 1, wherein the proportion of aliphatic fatty alcohol plus aliphatic fatty acid to aqueous-aliphatic glycol mixture in parts by weight is 1.5-4.5:45.

3. The sprayable pharmaceutical composition of claim 1, wherein the ratio of propellant to the sum of components (a), (b), (c), (d) and (e) is 1 part by weight to 9 parts by weight.

4. The sprayable pharmaceutical composition of claim 3, wherein the propellant is selected from the group consisting of propane, isobutane, dichlorodifluoromethane, dichlorofluoromethane, chlorodifluoromethane, 1,1,2-trichloro-1,2,2-trifluoroethane, dichlorotetrafluoroethane, carbon dioxide, nitrogen and mixtures thereof.

5. The sprayable pharmaceutical composition of claim 1 or 2, wherein the fatty alcohol used is cetyl alcohol.

6. The sprayable pharmaceutical composition of claim 1 or 2, wherein the fatty alcohol used is stearyl alcohol.

7. The sprayable pharmaceutical composition of claim 1 or 2, wherein the aliphatic acid used is stearic acid.

8. The sprayable pharmaceutical composition of claim 1 or 2, wherein the aliphatic acid used is palmitic acid.

9. The sprayable pharmaceutical composition of claim 1 or 2, wherein the aliphatic alcohol is cetyl alcohol and the fatty acid is stearic acid.

10. The sprayable pharmaceutical composition of claim 1 or 2, wherein the nonionic surface tension reducing agent is Igepal C0-630*.

11. The sprayable pharmaceutical composition of claim 1, wherein the nonionic surface tension reducing agent is Pluronic F-68*.

12. The sprayable pharmaceutical composition of claim 1, wherein the aliphatic glycol is propylene glycol.

13. The sprayable pharmaceutical composition of claim 1, wherein the microbicidally active agent is povidone-iodine.

14. The sprayable pharmaceutical composition of claim 1, wherein the microbicidally active agent is nonylphenoxyethyleneoxyethanol iodine.

15. The sprayable pharmaceutical composition of claim 1, wherein the microbicidally active agent is silver sulfadiazine.

16. The sprayable pharmaceutical composition of claim 1, wherein the microbicidally active agent is silver sulfathiazine.

17. The sprayable pharmaceutical composition of claim 1, wherein the microbicidally active agent is sulfamylon.

18. A method for preparing the sprayable composition of claim 1, comprising the steps of:
(a) mixing from 0.5 to 2.0 parts by weight of an aliphatic glycol selected from the group consisting of polyoxyethylene glycol, having a molecular weight of from 200 to 800, propylene glycol and glycerin with from 7.5 to 30 parts by weight of water;
(b) adding a nonionic surface tension reducing agent selected from the group consisting of poly(oxyethylene)-poly(oxypropylene)-polyethylene polyol compounds, the octylphenoxypoly(ethyleneoxy)-ethanol compounds, the fatty acid polyoxyalkyl esters of hexa-hydric alcohols, and mixtures of these, in concentration of at least equal to one-half but not greater than three times the combined weight of fatty alcohol and fatty acid moieties set forth in step (c) below;

(c) melting 0.5 to 2 parts by weight of a fatty alcohol selected from the group consisting of a fatty alcohol of the formula ROH, wherein R is a saturated or unsaturated alkyl group of from 10 to 18 carbon atoms in chain length, and from one to three parts by welght of a fatty acid of the formula RCOOH, wherein R is a saturated or unsaturated alkyl group of from 14 to 18 carbon atoms in chain length;
(d) mixing the molten fatty alcohol-fatty acid mixture of step (c) with the aqueous-glycol solution obtained as a result of step (b) and stirring until a homogeneous dispersion results;
(e) if necessary, adjusting the pH of the dispersion to a value not greater than 6;
(f) adding a therapeutically sufficient quantity of a germicidal agent and stirring until a homogeneous dispersion results;
(g) adding a pharmaceutically acceptable aerosol propellant which is gaseous at normal pressure and liquid at increased pressure, and packing into a suitable pressurized container fitted with a release valve.

19. The method of claim 17, wherein the fatty alcohol-fatty acid mixture of step (c) is mixed with the aqueous-glycol solution of step (b) in a proportion in parts by weight of 1.5-4.5:45.

20. The method of claim 17 or 18, further comprising the addition of suitable pharmaceutically acceptable buffers to maintain the pH of the concen-trate at between pH 4 and pH 6.