CA1075151A - Inhibiting production of undesirable products on body surfaces and environs - Google Patents
Inhibiting production of undesirable products on body surfaces and environsInfo
- Publication number
- CA1075151A CA1075151A CA317,237A CA317237A CA1075151A CA 1075151 A CA1075151 A CA 1075151A CA 317237 A CA317237 A CA 317237A CA 1075151 A CA1075151 A CA 1075151A
- Authority
- CA
- Canada
- Prior art keywords
- acid
- samples
- acid compound
- amino acid
- menstrual
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
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- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 208000002557 hidradenitis Diseases 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000029561 pustule Diseases 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical class O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229940080236 sodium cetyl sulfate Drugs 0.000 description 1
- GGHPAKFFUZUEKL-UHFFFAOYSA-M sodium;hexadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCOS([O-])(=O)=O GGHPAKFFUZUEKL-UHFFFAOYSA-M 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- WHNXAQZPEBNFBC-UHFFFAOYSA-K trisodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(2-hydroxyethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].OCCN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O WHNXAQZPEBNFBC-UHFFFAOYSA-K 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
The disclosure describes an absorbent catamenial dressing comprising an absorbent core and a liquid pervious cover around the core. The dressing contains within the struc-ture on at least the portions of the surface area thereof first to intercept menstrual fluids in use, an amino acid com-pound in an amount of at least about 0.001 gram per square inch. The dressing enables to control menstrual malodor, with-out significant kill of most bacterial flora.
The disclosure describes an absorbent catamenial dressing comprising an absorbent core and a liquid pervious cover around the core. The dressing contains within the struc-ture on at least the portions of the surface area thereof first to intercept menstrual fluids in use, an amino acid com-pound in an amount of at least about 0.001 gram per square inch. The dressing enables to control menstrual malodor, with-out significant kill of most bacterial flora.
Description
Thi~ applicakion is a dlvi~;ion O:e Application Serial No. 230,087, ~iled June 12, 1975.
The present invention is directed to methods and means ror controlling undesirable problem~ arising from mlcrobial action on body ~luids secreted or discharged f'rom the body.
One sf the long existing problems has been the unpleasant odors o~ menstrual fluid. Menstrual ~luid contains a variety of substances including proteins and lipids. Noxmally, present in menstrual ~luid are a wide number of gram negative and gram positive organisms which may act on these natural products. Bacterial action on proteins has been recognized as a source of amine malodor. Bacterial action on lipids could give rise to malodorous materials whlch are fatty acids.
Axillary malodor also has been a long existing problem.
Axillary sweat is composed o~ secretions of both eccrine and apocrine sweat glands whlch are present in the axillary area.
While eccrine sweat consi ~ largely o~ water and salt~ apocrine sweat is composed o~ a ~ariety o~ substances including protein3 c~rbohydrates and liplds. Numerous microorganisms including Staphylococci and Corynebacteria are present on the dermal ~urfaces o~ the axlllary region~ Microbial decomposition of lipids ln apocrine sweat which results in production of low~r :;
~atty acids has bee~ established as a primary cause o~ unpleasant odors in the axillary region. (Borick et alJ Anti_ crobial Agents Annual - 1960, pp~ 647-651, Plenum Press3 Inc., N.Y.) ''`, ' ;~ ' ~.
: -- 2 --.
L5~
PPC 1~5 Another problem, seemingl~r unrelated, ls inflammatory skin disorders such as acne. Sebum is a lipid mixture secreted by the sebaceous glands and having a variety of ~atty ~cids (Baughton et al~ J. In~est, Dermat, 33, 49-559 1959).
F~ee fatty aclds which have thelr source in the llpids are believed to be primarily responsible for the in~lammatory disorder of the skin known a~ acne vulgarls (Freinkel et al, New Eng. J. Med 273, 850-854, 1965). Microorganisms, especially Coryne~ cterium acne, an organism presenk in both normal and diseased ~ollicles~ are reported to cause the formation o~
fatty aclds (Scheimann et al, J0 Invest, Dermat4 349 171-174, 1960~
Germicides and antibiotics ha~e been emp~oyed for the control of unpleasant odors o~ body products such as perspira-tion and menstrual ~luid and for the alleviation o~ undesirable di~orders such as acne. T~us, hexachlorophene9 at one time was .
a popular constituent of preparatlons for controlling perspiration odors and antlbi~otics such a~ tetracycline have been ~uccessfully employ~ed in the treatment of acne~ However, germicldes and antlbiotics have accomplished these results by kill of the organisms, thereby disturbing the normal microbial balance.
As is well-known9 the kill of non-pathogenic organisms lnvites lnYasion by opportun~s~ organlsms such as pathogenlc baeteria, yeast or fungig whose presence may become mani~est in ~ebrile, in~lammatory, dermatitic or other undesirable response. Thus, it i~ deslrable th~t the control of unpleasant body odors or o*
disorders such as acne ar~sing from microbial actlon on llplds . .
7 5~ ~
be accomplished without significant k:ill o~ non-pathogenic microbial flora. It is further desirable that the results be accomplished without having adverse effects on hu~an subjects.
3 Other methods for the control of the undeslrable problems have been by the use o~ products which act on the causative a~ent after lts f'ormatlon. This approach is generai~y unsatisfactory tending to require employing relatively large amounts o~ treating agent and/or over an extended period. Moreover, the results have not ~een always ompletely satis~actory both in terms of completeness of control and in terms o~ avoidance o~ side reactions. It is highly desirable to control the undesirable problems by preventing the formation of the causative agent of these ~5 problems.
The present invenkion is based on the disco~ery that the foregoing problems as well as a number of other undesirable effects, ma~ be attributed to microorganisms acting in a ~; similar fashion and therefore, that the various p~oblems may ~O be controlled in a similar manner. It has further been discovered that this control may be brought about without -` significant kill of most bacterlal flora.
.', ' ' ,' It has been discovered according to the present invention that many of the undesirable problems such as menstrual malodor, - , ' 4 :: :
:~7~
axillary malodor and inflammatory disorders such as acne, caused by formation of undesirable products on body surfaces and environs as a result of microbial action on lipoidal mat-erials in body secretions may be alleviated by inhibiting the formation of the undesirable products by applying to the situ~
of formation of the undesirable products, an inhihitory amount of an amino acid compound.
More specifically, tlle invention relates to an ab-sorbent catamenial dressing comprising an absorben~ core and a liquid pervious cover around said core, said dressing contain~
ing within the structure on at least the portions of t'he surface area thereof ~irst to intercept menstrual fluids ln use, an amino acid compound in an amount of at least about OoO01 gram per square inch.
By "lipoidal materials in body secretion" i~ meant lipids (as understood in chemical terminology~ which are pres-ent in body fluids which are secreted, excreted, discharged or exuded. Thus, "secretions" as herein employed include waste fluid~ Typical secretions are sebum, perspiration, menstrual fluid, etc..
Lipids of importance in the present context are not only triglycerides but also phospholipidsO The triglycerides may be represented by E'ormula I:
Il CH2 ~ 0-C-R
.''~ I fi~ .
I ~ I
CH2 -o-c -R
wherein in this and succeading formulas, each R is a hydro-carbon radical derived from fatty acids and may be same or different. The phospholipids of primary concern in the present context are phosphotriglycerides which may be . . ... .
, 7 ~
represented by the formula:
CH2-0 C~P~
. O
:H-O-C R
O
II
. H~-O- i-O-B
. , .
wherein R is as previousl~ de~ined and B is a residue o~ an alcohol-amine cornpound such as an amlno alcohol, a hydroxy- -quaternary ammonium base or a hydroxyamlno acid~
.. . .
.~ The products which are formed or may be ~ormed by ~; microbial actlon on lipoidal materials are slmllar to those whlch may be formed on ch~mical hydrolysis. Thusg ratty acids and glycerol are produced f'rom the triglycerides o~
Formula I as follows:
.~ ' CH20H .
, ; I ~ ~ C~OH ~t 3 RCOOH
''' I .
~, ' C~OEI
~, .
Slnceeach R may be d~fferent, various ~atty acids may be formedO
. ~mong the acids which may be formPd are malodorous lower fatty .; ~cids such as butyric, isobutyric~ iso~alerlcJ etcO which are `: problems ln ~xillary and menstrual malodorO These and other ~atty acids including hlgher fatty acids (to Clg) may be sources i o~ other undesirable problems such as infla~matory disorders Or the skin.
7 S~ ~ ~
Fatty acids may also arise from the phospholipids Or Formula II:
, CH~OH
., CHOH ~ 2 RCOOH ~ H3PO4 ~ BO~
In preliminary experiments hereinaf'ter described~ phospholipids as a source o~ malodorous fatty acids was established.
'' It is ~urther recognized that the undesirable fatty aci~s may arise in other ways as a result of microbial action and control of such ~atty acids are intended to be embraced.
Howe~er, the foregoin~ is believed to be a major source o~
fatty ac~ds. -, ~ - .
The expression "situ~ o~ formation" refers to the loci where the lipoidal secretions are retained or received and .. , ~.;
subject to microbial attack.
Normally~ the "situs of formation" o~ primary concern are body or dermal sur~aces and environs. These includa skin, `~ 15 vagina and materials in ~lose proxlmity to body sur~aces such as catamenial devices, clothing, bed pads, etcO which are ;~
intend~d to receive or do receive the body fluids.
.. :
. ~ .
~ 7 1~75~1 Amino acid compounds use.ful f'or the practice of the present invention generally have in the structure at least one arrangement of the amln~ group to acid group as follows:
.
l` l amino~ C ~ tC)o 1~ acid . . I 1 .
The acid group is pre~erably carboxyllc, -COOH~ but may be sulfonic, -SO20H, or phosphonic, ~PO(OH)2. The amino may be substituted and the carbon chaln may contain groups such as hydroxyl -OH, sulfhydryl ~SH~ and ether ~O-. Generally more -~han one acid containing group is present in the molecule andrthe acid containing group may be attached to the same amino nitrogen. The compounds may be termed ~'amino polyacid compounds . "
An important group of compounds which inhibits the rormation of fatty aclds are the aminopolycarboxylic acid compounds. By "aminopolycarboxylic acid compound'l is meant an amino acid or water-soluble salt thereo~ in which there is two or more substituent groups of the general skructure:
: ' , . '~.
_ ~ l ~ ~ ( c ~o ~ ~ COOH
~' I . I ' in ~he molecule which are attached to'one or more amino groups.
. Where there are more than two such substituent groups, the excess ;
carboxyl groups may be esterified as long as at least two of the ~ ~oregoing groups are present.
.
. ~ .
~7~5~
PPC 1~5 Preferred salts, e~peclally ~or certain applications are monovalent salts such as sodiwn and potasslum salts. For certain other applications~ alkanolamine salts are preferred, especially di- and trialkanolamines such as triethanolamlne, diethanolamine, triisopropanolamlne, etc. The besk known aminopolycarboxylic acid compounds are the acid~ and salts of ethylenediaminetetraacetic (EDTA) acid, diethylenetriamine pentaacetic (DTPA) acld and N-~hydroxyethylethylenediaminetria acetic (HEDX'A) acid, These compounds are available ~ 10 commercially through trade names such as VERSENE3 VERSENEX, ; VERSENOL, SEQIJESTRENE, etc. Other typical compounds in . this class include triethylenetetraamlnehexaacetlc acid~
1,2-diaminocyclohexane-N~N'-tetraacetic acid, NgN-dihydroxy-eth~lethylenediaminediacetic acid, iminodiacetic acid, ~5 hydroxyethyliminodiacetic acid, and nitrilotrlacetic acid and their salts as well as the propionic acid analogs.
Other compounds include N~N'-dihexadecyl ester of ethylenediam netetraacetic acid, N,N'-dioctadecyl ester o~
: et~hylenediaminetetraacetic acid~ Ng~'-di(15-carboxypentadecyl) 20 ester o~ ethylenediaminetetraacetic acld, N-(~5-carboxy 9-; pentadecnyl)iminobis(ethylenenitrllo)tetracetic acid, N- -methoxyethyl-~iminodiacetic acid, ethylenebis(oxypropylamino-diacetic acid)~ ethylenebis(oxyethyliminodiacetic acid)~
aminoethyl-N--methyliminodiacetic acid, a-mercaptoethylimino-diacetic acid, a-methylmercaptoethyliminodiacetic acid, etc.
., .
! .. ~, . ~ 9 .~:
~ ~ . . . , , ~ . .. ..
3L~97S~Sl Amino acid compounds o~ other classes which are Or special interest for certain applications are those which also have more than one acid group containing substituent attached to the amino group but in which the acid groups are generally phosphonlc or sulfonic. Howe~er, these amino acid compoun~s may have mixed acid groups, i.e., have one or more carboxyl groups in the same molecule as that containlng the phosphonic or sulfonic acid groups. Representative amino acid of this type include ethylenediaminotekra(methylene-O phosphonic acid), nitrilstris(methylenephosphonic acid), iminobis(methylenesulfonic acid), aminomethylphosphonic acid-(N,N-diacetic acid), etc.
, ' "
- The amino acid compounds are available as free acids~
acid salts and salts. It is pre~erred that the ~orm o~ the ; 3 amino acid compound or combination thereof employed be suchthat at the situs o~ operation, the pH be near neutrality, about 6.2 to about 8.5. However, useful results may be obtained i~ the pH is at least as high as 4.o. FrequentlyJ
- it is convenient to prepare the salt or acid salt by mixing ~ ~ theracid and base in the composition, ,`, ~ The amino acid compounds are useful in such amounts , . . -as would give a final concentration of at least 0.01~ by weight o~ the body secretion. The upper limit is dictated primarily by practical considerations. Generally ~peak~ng, not much advanta~e is gained by adding an amount which ~ould give a concentration greater than about 0.5% by welght of : !
'' ' 75~5~
PE'C 185 body secretion. The pre~erred amounts depend on the purpose, place and method o~ application and on the particular compound. Thus9 where microbial population læ expected to be high, such as in menstrual f'luid, larger amounts preferably are employed. Thus, ~or control of menstrual malodorJ at least about 0.04% by weight of menstrual ~luld ~ deslrable and 0.10% or more is preferred.
Within the broad scope, pre~'erred ranges are hereina~ter disclosed ln the context o~ the particular use and method of application.
The amino acid compound may be applied to the situs : Or formation o~ microblally produced undesirable prod~cts ln various ways. In its use for the inhlbition of ~ormation o~ malodorous materials ln menstrual fluldg th~ amlno acid compound is conven~ently applied to receptacles ~or the *luid such as catamenial dressings or to such other material~
which may receive the fluid such as bed pads~ clo~hingJ etc.
. By "catamenial dressings" is meant sanitary napkinsJ tampons and interlabial pads which usually conslst o~ a core o~ one .~ ~0 or more la~ers o~ highly absorbent, relatively dense materials which have a flu1d permeable~ æoftg knitted, woven or non ~oven wrapper~ The cores are conventionally made ~f layers ;:
o~ fibers such as carded cotton webs~ air-layered cellulosic fiber webs, comminuted wood pulp bats, tissue pulp or like ~5 materials but may be made of newer synthetic mater~als such as synthetic polymer ~oams and fibers. Although the amino :~ ~cid compound may be.distributed uniformly thrDugh the !
-~7~i~S~
PPC 1~5 catamenial dressing, lt is more userul to place ik ln that portion which flrst contacts the body dlscharge, Thus, lt is preferably applied to the surface of the absorbent cores of the dressings or to the covers or both in such a manner that the amlno acid compound is presenk on the sur~aces thereo~ in an amount ranging from about 0.001 g. per square lnch to about 0.1 g. per square inch. Such amounts have been found to pro~ide the desired concentration in terms o~
the amount o~ amino acid compound to total body secretion.
A preferred range ~or catamenial dressings ls from about 0~004 to 0. o6 g . per square inch.
.
The amino acid compounds may be applied to the cata- 7 menial dress1ngs during manufacture or use. When applied during manu~acture, it may be applied by spraying either an aqueous spray or an aerosol spray, pad~ ng, soaklng, or by ..
dustlng or any known method ~or applying materials thereko.
An aerosol spray may employ such propellants as dichloro-di~luoromethane, tri~hlorofluoromethane; a solvent spray may employ substantially inert solvents such as isopropanol.
The use of a propellant or inert organic solvent is preferred over an aqueous solution or suspension to minimize drying o~ the catamenial dressing subsequent to the application of the amino acid compound. In addition~ the amino acid comp~und may be applied to the dress~ngs prior to use in dry powder ~ormulationsc ' ,; .
.~ "
: ' "' ` " ' ~ ' ' ~' '' . , 5~
The application of the amino acid compoun~ may be made topically to the dermal surfaces pre~erably in a suitable carrier such that it is distributed on the dermal surfaces in amounts sufficient to provide at least 0.01% by weight of body secretion as hereinbefore specified. The application preferably is made prior to the secretion of the body fluid to preclude substantially completely the forrnation of the undesirable pro-ducts. However, application may be made subsequent ther~to by minimizing microbial action on the body secretions. Topical applications ~o dermal surfaces are suitable for inhibiting malodor development~ When the application is to be topical, the carrier may be in solid, liquid, spray or semi solid form in cosmetic or pharmaceutical carriers intended for topical use.
Carriers into which the amino acid compound may be incorporated include lotions, ointments, aerosols, water solutions, creams, pulverized mixtures, geI sticks and the like. me various additives and diluents include ointment additives such as poly-sorbate 80, polyoxyethylene sorbitan trioleate; surfactants and emulsifiers such as lauryl sul~ate, sodium cetyl sulfate, glyceryl monostearate, diethylaminoethyl alkyl amide phosphate, isopropyl myristate, octyl alcohol, glyceryl and ylycol esters of stearic acids: glycols such as propylene glycol, other polyhydroxy compounds such as glycerol, sorbitol, alcohols such as ethanol, isopropanol, witch hazel (Hamameli~ water~;
perfumes: essential oils, propellants such as halogenated !
hydrocarbons, e.g., dichlorodi~luoromethane, trichlorofluoro~
ethaneJ etc., carbon dioxide and nitrogen; solid diluents such as calcium carbonate, starch~ bentonite, talc; and silicone-type fluids such as polysiloxane fluid. Selection o~ the particular carrier varie~; with use. In dermal preparations for the control Or inflammatory skin condltions, aqueous compositlons are desirable. Preferred compositions for such applications are khose comprising wikch hazel as a carrier component.
In compositions for topical application, the amino acid compound is employed in an amount of at least 0.05~ by .welght. This is desirable in ~iew of the diluting and possible partial deactivating effect o~ the carrier. The amino acid compound may be present in larger amounts and may even constitute the major portion of the composition although less desirable from practical considerations. For topical application, the amino acid compounds are preferably employed i~ the form o~ alkanolamine salts. When the carrier is aqueous, the salt may be formed in the composition by admixing the free acid and the alkanolamine in the aqueous carrier.
' ` ' . ' , .
~ .
.~' ..
. , .
"'; ~ ' , '.' . . ': :, , 7 ~
PPC 1~5 In preparatiorsfor the control of inrlan~atory skin conditlons, the amino acid compounds employed are preferably in the form of acid or water soluble mono-valent salt or mixtures therelof in an aqueous composition ln an amount of from about ~ to about 15% by weight when based on the weight o~ free ~cid.
When incorporating the amino acid compound into a lotion, cream or aerosol, the amlno acid compound may be added in a solvent compatlble with the system in which it is incorporated such as water~ glycerol~ propylene glycol, tripropylene gl~colJ methyl ether, ethanolJ etc. Alternatively, - ~he amino acid compound may be added to the ~inal composition : and int~mately admixed therewith~ Such would be the pre~erred . method for preparing dusbng powders as well as aqueous ~5 solutions such as in witch hazel.
The compositions abov~ described are applied to the situs o~ production o~ undesirable materlals by the various microorganisms. The ml~roorganisms associated with the production of materials contributing tv menstrual malodor include Gram Negatlve or~anisms such as Proteus mir ebs1ells ~ ~ Aerobacter ~ 5 Escherich~s c~
Pseudomonas ,~eruginosa~ etc. J Gram Positi~e organisms such as s aureus, ~ cc~ faecal _~ etc~ and yeast ~` such as Candida ~ , etc. The mlcroorganlsms associated with the pro~uction of' substances contributing to axll3~ry . ..
!
. . .
~s~
P~C 1~5 malodor are those normally present on the skin surfaces of which those of the genera Cor~nebacte~rium and - , Staphylococcus are the most important. Coryn,ebac-teria are also associated with the production of acids contri-buting to the undesirable in~lammatory condltlons o~ the skin. By employing the compounds and compositions in accordance with the present 'inventlon, the action o~
the microorganisms which results in the production of undesirable acids is somehow inhibited or al~ered, The amino acid compound is believed to be proceeding by removal of the necessary metallic co-factor for the . . .
enzymatic production of fatty acids~ HOwever, the lnven-tlon is not llmited to any particular theory and the preventative control of fatty ac-ld productlon may be ~' 15 achieved without necessaril,y causing detrimental e~fect on microbial ~lora.
The ef~ectiveness of the amino acld compound in inhibiting the formation of undesirable fatty acids from lipids was determined by gas chromatographic analyses and the effectiveness in odor control was determined by organ-'~ ~0 oleptic techniques.
. .
'~ Gas chromatographic analyses employed comparisons with known acids. The method employed was as ~ollows:
., . .
! 16 .~
..... , .. , . .. , ... .. , ., . , ~ ., . ", . " .. .. .
~5~.
PPc L85 Fatty acids extracted in diethyl ether frcm acidified test samples were determined by gas chromatvgraphic procedures using a Hewlett-Packard 76XOA instrument and Porapak ~S 80/100 mesh in a 6 ft. x 2mm. I,D. glass col~n. The instrument was pro grammed from 135 c to an upper limit o~ 235 c at the rate of 4 C temperature rise per minute, holding the upper limit~ for ~ix minutes. Helium was used as a carrier gas at a pre~ure of 60 PSI and a flow rate of 40 ml./m.in.
For ev~luation o~ the ~fectiveness o~ catamenial ; O dressin~s in odor control~ quantitative organoleptic evaluation method was employed referred to as the Modified Ratio Scale Organoleptic Evaluation method as follows, ' , " , The Modified Ratio Scale Organoleptic Evaluation Method -i This method is devised so that data obtalned ~rom an organoleptic appraisal panel may produce an evaluat,ion of a sample characterized as an absolute value ~or odor intensity.
Thus, not only can the dif~erence between two samples o~ an odorant placed in di~erent en~ironments (e~g.g on a pad . -.
w~th and without deodorizer) be detected~ but further, the evaluation will indicate, quantitatively3 as to whether the , ~ odor intensities o~ the ~amples are strong or wealcO For - example, one sample may contain a deodorizer which i5 many tlmes as ef~ectlve as that contained in a second sample~
This notwithstandlng, both deodorizers may only produce a small decrease in the odor intensity, all of which is indicated by the sub~e~t evaluation methodO
' `, ' .
:.: . ; : . : . . . . . . . .
.'LO'7S~5i$
PPC 1~5 The flrst step in this method is to determine the threshold concentration of the odorant, The method used is described by Fred H~ Steiger in Chemlcal Technology, Volume 1, pg, 225, April 1971, wherein the dekerminati.on o~ the odor threshold concentration for ethylamlne is describedJ applying the Weibull distribution ~unction.
Generally~ this procedure requlres the gathe~ing Or organoleptic data from a panel presenked with a series of sa~ples containing odorant in increasing concentrations in order to determine the concentratlon level at which an arbitrary percentage of the paneli~ts can detect the odor.
For the purposes of the current, evaluation that arbitrary percentage is chosen as the cumulative 50% level, As so determined, the threshold concentration o~ the odorant isPspeci~ic to the odorant and the condltions of the sampling procedure.
- The method employed herein ~or panel evaluation is to present each panelist with a series o~ samples, ln a ~ampling apparatus which conslsts of an opaque, one pint~
polyethylene Mason Jar having a pol~ethylene screw cap fitted onto :Lts neck. The ~ar is internally lined with a polyethylene bag and a Buchner funnel is fitted about ~he cap, wlth the narrow outlet portion of the ~unnel, below the ~ilter plate of the funnel, extending through the cap and into the llned jar. A sample is placed in the jar, the Jar is capped wit,h the Buchner funnel fitted in place and a watch glass is placed across the wide inlet portion o~ the funnel.
.
~: ' ~ 1 ,~
..; ,;
. .. ~
~7S~L5~
PPC 1~5 The sample is then allowed to equilibrate for one hour at ambient conditions. For the purpose o~ the threshold determination, the samples each comprise a specific concentration of the odorant in a water solution, a total o~ 3 ml. o~ solution being placed in the jar. A panel o~
about 30 women are presented with a series Or equilibrated samples o~ increasing concentration and, start~ng with a sample at zero concentration (water only), are asked to report the ~irst sample having a detectable odor. The panellsts are instructed to snif~ each sample in turn, pausing 30 seconds between samplings. The accumulated data is organized to establish the cumulative percentage of the panel which detects an odor at each concentration level correspondlng to each sampleO The data7 ~o organized, is plotted as described in the a~orementioned Steiger article on Weibull Probability Paper with the concentrakion as the abscissa and the cumulative percentage of the panel as the ordinate. The concentratlon ak 50~ is then taken as the threshold concentrationD
~0 Havlng established the threshold value, the ~odified Ratio Scale Method is applled by preparing a master curve.
Using the same testin~ apparatusJ a series of samples are prepared and presented to the panel wherein the concentra-tlons o~ odorant can be expressed as multiples of the threshold concentration or odor unlts. One of these samples is 20 t~mes the threshold concentration (20 odor units)O
:
., .:
.~
~ ~ . . . .. . .
s~
PPC 1~35 In accordance with the standard method of Ratio Scaling, each panelist is asked to evaluate the set of samples berore her and to assign a value to the odor inten-slty of each sample in proportion to the intensity of the other samples, The panelists are ~ree to choose whatever scale they wish. For exampleg a panelist may ~ssign 10 to the strongest sample. A sample having half that i.ntensity~
in accordance with this panelist's evaluatlon, would then be assigned a value o~ 5. The accumulated data then consists Or a series of evaluations ~or each panellst, each serles being bas~d upon the individual panelists' scale. Arbi-trarily~ a ratio scale value of 100 is assigned to the sample concentration of 20 times threshold concentration. Each of the panelists' evaluations are then proportioned to bring their individual scales to the basis of 100 for 20 times threshold concentration. For ex~nple, the evaluations of a panelist assigning a value of 10 to a firsk sample having a concentration o~ 20 times threshold concentratlon will be proportioned to show, for that panelist~ a value of 100 ror the flrst sample and a ~alue o~ 50 ~or tile second sample.
me data is now organized so that, ~or each sample corres-ponding to a specific multiple of the threshold concentration, there is a series o~ Ratio Values, all on the same scale (20 timPs Threshold Concentration -- 100) corresponding to each panelist's evaluation o~ this sampleO The geometric means o~ the ratio values for each sample is calculated and that value is taken as the Ratio Value for that multiple of threshold concentration.
,, - ,. .. .
. . . ..
.. ~ . . . . . . . .
~75~
When the log of the Ratio Value is plotted, as the ordinate, against the lo~ o~ the multiple of threshold concentration, a straight line, ~itted to the data points between 3 to 20 times threshold concentration gives an excellent correlation.
It has been discove~ed that irrespective of which amine odorankis testedJ when a threshold concentratlon is determined ~or that specific odorantand the method ~ constructing a Master Cur~e as described above is followed, the resultlng Master Curves are superimposable between multiples of thres~
hold concentration of about 3 to about 20.
, The curve obtalned ln this way ~or isobutyric acid, a chemically dissimilar material also was superimposable on the Master Curves *or the amines. Thus, the reference odorant in any test may be chemically dissimilar to the odor constltuent or constituents belng tested. ~~
The Master Curve may now be used to evaluate the odor intensity of any odorant when placed in any environment such as, for example, on a pad of untre,,-~ted cellulosic ~ibers or :
on a pad of ~ibers containing deodorizing material and, in addi~ion to obtaining comparisons between the relative inten-sity o~ the samples tested, an absolute measure of the intensity o~ each samp:Le may be obtained. To do this, the p~nel is presented with a series o~ samples, one of which is a standard sample consisting o~ known concentrat~on o~ the odorant being tested in an enYironment identical to that . ' ~1 ": . ~ , .
3L~7~LS~
PPC 1~35 used in producing the Master Curve~ Preferably, this standard sample is chosen as having 20 times the threshold concentration arld hence, a Ratio Value of 100 on the Master Curve.
The panelists are again asked to evaluate the series of samples usln~ whatever scale they choose. ~ased on the value which each panellst gives to the intensity of the standard sample, all other values given by the paneli.sts are proportioned so as to be consistent with the rating Or the standard sample, e.g.~ a panelist asslgning a value of 50 to the standard sample and 5 to a second sample of ~ unknown intensity will have these values proportioned so the standard will be given a Ratio Value of 100 and the unknown sample given a Ratio Value of 10. By referring to the Master Curve, lt can be determined that the panelists now proportioned Ratio Value of 10 for the ~,econd sample is equivalent to an odor intensity of a certain number of multiple~ o~ threshold concentration as read ~rom the Master Curve were 1.2, the odor intensity o~ the s~mple of unknown intensity, in the test environment, is the same as a sample having an odorant concentration o~ 1.2 times the threshold concentration in the standard environment.
Prel.iminary determinations were made in connection with the menstrual malodor aspect o~ the present invention to establish the presence of phospholipids in menstrual ~luid and to establish malodorous fatty acid production by microbial flora commonly present in menstrual fluid~
--~ .. .. .
The presence of s~gnificant amounts of phosphollpids in menstrual fluid was established by a procedure consisting of heating the phospholipids with perchloric acid to oxidize the organic portion of the molecule and convert the phosphorus to a blue phosphomolybdate which may be read colorimetrically as more fully described on pp. 375-376 o~ "Bray's Clinical Laboratory Methods" by Bauer et al, 17th Edition, C. W. Mosby Co., 1969. Ten samples of menstrual fluld were collected in cups and subJected to phospholipid analyse~ The analyses established the presence o~ ~rom 2250 to 4140 ppm of phospho lipids amounting to ~rom 0.225 to 0.4% of the fluid.
To establish the ability of microorganisms commonly present in menstrual ~luld to produce malodorous fatty acids, separate samples of sterile human blood were inoculated with dir~erent organisms previously lsolated from menstrual fluid, f~llowed by incubation and analysis by gas chromatogr~phy as hereina~tar described. In the determination~ blood was employed in~tead of menstrual fluid because o~ ~he avaiLability of sterlle blood and the desirability of a sterile substrate to identi~y ~atty acid production as being caused by the organism used ln lnoculation, The suitability o~ substituting blood was based on the known fact of the presenee of triglycerides in both blood and men~trual fluld and on pre~iminary experi- -ment~ on ~ix samples e~ch of human blood and menstrual fluid which showed average total phospholipids to be 2807 ppm and 2771 ppm respectively. The methods employed and the resul~s obtained were as follows:
~3 .
~5~ ~
The present invention is directed to methods and means ror controlling undesirable problem~ arising from mlcrobial action on body ~luids secreted or discharged f'rom the body.
One sf the long existing problems has been the unpleasant odors o~ menstrual fluid. Menstrual ~luid contains a variety of substances including proteins and lipids. Noxmally, present in menstrual ~luid are a wide number of gram negative and gram positive organisms which may act on these natural products. Bacterial action on proteins has been recognized as a source of amine malodor. Bacterial action on lipids could give rise to malodorous materials whlch are fatty acids.
Axillary malodor also has been a long existing problem.
Axillary sweat is composed o~ secretions of both eccrine and apocrine sweat glands whlch are present in the axillary area.
While eccrine sweat consi ~ largely o~ water and salt~ apocrine sweat is composed o~ a ~ariety o~ substances including protein3 c~rbohydrates and liplds. Numerous microorganisms including Staphylococci and Corynebacteria are present on the dermal ~urfaces o~ the axlllary region~ Microbial decomposition of lipids ln apocrine sweat which results in production of low~r :;
~atty acids has bee~ established as a primary cause o~ unpleasant odors in the axillary region. (Borick et alJ Anti_ crobial Agents Annual - 1960, pp~ 647-651, Plenum Press3 Inc., N.Y.) ''`, ' ;~ ' ~.
: -- 2 --.
L5~
PPC 1~5 Another problem, seemingl~r unrelated, ls inflammatory skin disorders such as acne. Sebum is a lipid mixture secreted by the sebaceous glands and having a variety of ~atty ~cids (Baughton et al~ J. In~est, Dermat, 33, 49-559 1959).
F~ee fatty aclds which have thelr source in the llpids are believed to be primarily responsible for the in~lammatory disorder of the skin known a~ acne vulgarls (Freinkel et al, New Eng. J. Med 273, 850-854, 1965). Microorganisms, especially Coryne~ cterium acne, an organism presenk in both normal and diseased ~ollicles~ are reported to cause the formation o~
fatty aclds (Scheimann et al, J0 Invest, Dermat4 349 171-174, 1960~
Germicides and antibiotics ha~e been emp~oyed for the control of unpleasant odors o~ body products such as perspira-tion and menstrual ~luid and for the alleviation o~ undesirable di~orders such as acne. T~us, hexachlorophene9 at one time was .
a popular constituent of preparatlons for controlling perspiration odors and antlbi~otics such a~ tetracycline have been ~uccessfully employ~ed in the treatment of acne~ However, germicldes and antlbiotics have accomplished these results by kill of the organisms, thereby disturbing the normal microbial balance.
As is well-known9 the kill of non-pathogenic organisms lnvites lnYasion by opportun~s~ organlsms such as pathogenlc baeteria, yeast or fungig whose presence may become mani~est in ~ebrile, in~lammatory, dermatitic or other undesirable response. Thus, it i~ deslrable th~t the control of unpleasant body odors or o*
disorders such as acne ar~sing from microbial actlon on llplds . .
7 5~ ~
be accomplished without significant k:ill o~ non-pathogenic microbial flora. It is further desirable that the results be accomplished without having adverse effects on hu~an subjects.
3 Other methods for the control of the undeslrable problems have been by the use o~ products which act on the causative a~ent after lts f'ormatlon. This approach is generai~y unsatisfactory tending to require employing relatively large amounts o~ treating agent and/or over an extended period. Moreover, the results have not ~een always ompletely satis~actory both in terms of completeness of control and in terms o~ avoidance o~ side reactions. It is highly desirable to control the undesirable problems by preventing the formation of the causative agent of these ~5 problems.
The present invenkion is based on the disco~ery that the foregoing problems as well as a number of other undesirable effects, ma~ be attributed to microorganisms acting in a ~; similar fashion and therefore, that the various p~oblems may ~O be controlled in a similar manner. It has further been discovered that this control may be brought about without -` significant kill of most bacterlal flora.
.', ' ' ,' It has been discovered according to the present invention that many of the undesirable problems such as menstrual malodor, - , ' 4 :: :
:~7~
axillary malodor and inflammatory disorders such as acne, caused by formation of undesirable products on body surfaces and environs as a result of microbial action on lipoidal mat-erials in body secretions may be alleviated by inhibiting the formation of the undesirable products by applying to the situ~
of formation of the undesirable products, an inhihitory amount of an amino acid compound.
More specifically, tlle invention relates to an ab-sorbent catamenial dressing comprising an absorben~ core and a liquid pervious cover around said core, said dressing contain~
ing within the structure on at least the portions of t'he surface area thereof ~irst to intercept menstrual fluids ln use, an amino acid compound in an amount of at least about OoO01 gram per square inch.
By "lipoidal materials in body secretion" i~ meant lipids (as understood in chemical terminology~ which are pres-ent in body fluids which are secreted, excreted, discharged or exuded. Thus, "secretions" as herein employed include waste fluid~ Typical secretions are sebum, perspiration, menstrual fluid, etc..
Lipids of importance in the present context are not only triglycerides but also phospholipidsO The triglycerides may be represented by E'ormula I:
Il CH2 ~ 0-C-R
.''~ I fi~ .
I ~ I
CH2 -o-c -R
wherein in this and succeading formulas, each R is a hydro-carbon radical derived from fatty acids and may be same or different. The phospholipids of primary concern in the present context are phosphotriglycerides which may be . . ... .
, 7 ~
represented by the formula:
CH2-0 C~P~
. O
:H-O-C R
O
II
. H~-O- i-O-B
. , .
wherein R is as previousl~ de~ined and B is a residue o~ an alcohol-amine cornpound such as an amlno alcohol, a hydroxy- -quaternary ammonium base or a hydroxyamlno acid~
.. . .
.~ The products which are formed or may be ~ormed by ~; microbial actlon on lipoidal materials are slmllar to those whlch may be formed on ch~mical hydrolysis. Thusg ratty acids and glycerol are produced f'rom the triglycerides o~
Formula I as follows:
.~ ' CH20H .
, ; I ~ ~ C~OH ~t 3 RCOOH
''' I .
~, ' C~OEI
~, .
Slnceeach R may be d~fferent, various ~atty acids may be formedO
. ~mong the acids which may be formPd are malodorous lower fatty .; ~cids such as butyric, isobutyric~ iso~alerlcJ etcO which are `: problems ln ~xillary and menstrual malodorO These and other ~atty acids including hlgher fatty acids (to Clg) may be sources i o~ other undesirable problems such as infla~matory disorders Or the skin.
7 S~ ~ ~
Fatty acids may also arise from the phospholipids Or Formula II:
, CH~OH
., CHOH ~ 2 RCOOH ~ H3PO4 ~ BO~
In preliminary experiments hereinaf'ter described~ phospholipids as a source o~ malodorous fatty acids was established.
'' It is ~urther recognized that the undesirable fatty aci~s may arise in other ways as a result of microbial action and control of such ~atty acids are intended to be embraced.
Howe~er, the foregoin~ is believed to be a major source o~
fatty ac~ds. -, ~ - .
The expression "situ~ o~ formation" refers to the loci where the lipoidal secretions are retained or received and .. , ~.;
subject to microbial attack.
Normally~ the "situs of formation" o~ primary concern are body or dermal sur~aces and environs. These includa skin, `~ 15 vagina and materials in ~lose proxlmity to body sur~aces such as catamenial devices, clothing, bed pads, etcO which are ;~
intend~d to receive or do receive the body fluids.
.. :
. ~ .
~ 7 1~75~1 Amino acid compounds use.ful f'or the practice of the present invention generally have in the structure at least one arrangement of the amln~ group to acid group as follows:
.
l` l amino~ C ~ tC)o 1~ acid . . I 1 .
The acid group is pre~erably carboxyllc, -COOH~ but may be sulfonic, -SO20H, or phosphonic, ~PO(OH)2. The amino may be substituted and the carbon chaln may contain groups such as hydroxyl -OH, sulfhydryl ~SH~ and ether ~O-. Generally more -~han one acid containing group is present in the molecule andrthe acid containing group may be attached to the same amino nitrogen. The compounds may be termed ~'amino polyacid compounds . "
An important group of compounds which inhibits the rormation of fatty aclds are the aminopolycarboxylic acid compounds. By "aminopolycarboxylic acid compound'l is meant an amino acid or water-soluble salt thereo~ in which there is two or more substituent groups of the general skructure:
: ' , . '~.
_ ~ l ~ ~ ( c ~o ~ ~ COOH
~' I . I ' in ~he molecule which are attached to'one or more amino groups.
. Where there are more than two such substituent groups, the excess ;
carboxyl groups may be esterified as long as at least two of the ~ ~oregoing groups are present.
.
. ~ .
~7~5~
PPC 1~5 Preferred salts, e~peclally ~or certain applications are monovalent salts such as sodiwn and potasslum salts. For certain other applications~ alkanolamine salts are preferred, especially di- and trialkanolamines such as triethanolamlne, diethanolamine, triisopropanolamlne, etc. The besk known aminopolycarboxylic acid compounds are the acid~ and salts of ethylenediaminetetraacetic (EDTA) acid, diethylenetriamine pentaacetic (DTPA) acld and N-~hydroxyethylethylenediaminetria acetic (HEDX'A) acid, These compounds are available ~ 10 commercially through trade names such as VERSENE3 VERSENEX, ; VERSENOL, SEQIJESTRENE, etc. Other typical compounds in . this class include triethylenetetraamlnehexaacetlc acid~
1,2-diaminocyclohexane-N~N'-tetraacetic acid, NgN-dihydroxy-eth~lethylenediaminediacetic acid, iminodiacetic acid, ~5 hydroxyethyliminodiacetic acid, and nitrilotrlacetic acid and their salts as well as the propionic acid analogs.
Other compounds include N~N'-dihexadecyl ester of ethylenediam netetraacetic acid, N,N'-dioctadecyl ester o~
: et~hylenediaminetetraacetic acid~ Ng~'-di(15-carboxypentadecyl) 20 ester o~ ethylenediaminetetraacetic acld, N-(~5-carboxy 9-; pentadecnyl)iminobis(ethylenenitrllo)tetracetic acid, N- -methoxyethyl-~iminodiacetic acid, ethylenebis(oxypropylamino-diacetic acid)~ ethylenebis(oxyethyliminodiacetic acid)~
aminoethyl-N--methyliminodiacetic acid, a-mercaptoethylimino-diacetic acid, a-methylmercaptoethyliminodiacetic acid, etc.
., .
! .. ~, . ~ 9 .~:
~ ~ . . . , , ~ . .. ..
3L~97S~Sl Amino acid compounds o~ other classes which are Or special interest for certain applications are those which also have more than one acid group containing substituent attached to the amino group but in which the acid groups are generally phosphonlc or sulfonic. Howe~er, these amino acid compoun~s may have mixed acid groups, i.e., have one or more carboxyl groups in the same molecule as that containlng the phosphonic or sulfonic acid groups. Representative amino acid of this type include ethylenediaminotekra(methylene-O phosphonic acid), nitrilstris(methylenephosphonic acid), iminobis(methylenesulfonic acid), aminomethylphosphonic acid-(N,N-diacetic acid), etc.
, ' "
- The amino acid compounds are available as free acids~
acid salts and salts. It is pre~erred that the ~orm o~ the ; 3 amino acid compound or combination thereof employed be suchthat at the situs o~ operation, the pH be near neutrality, about 6.2 to about 8.5. However, useful results may be obtained i~ the pH is at least as high as 4.o. FrequentlyJ
- it is convenient to prepare the salt or acid salt by mixing ~ ~ theracid and base in the composition, ,`, ~ The amino acid compounds are useful in such amounts , . . -as would give a final concentration of at least 0.01~ by weight o~ the body secretion. The upper limit is dictated primarily by practical considerations. Generally ~peak~ng, not much advanta~e is gained by adding an amount which ~ould give a concentration greater than about 0.5% by welght of : !
'' ' 75~5~
PE'C 185 body secretion. The pre~erred amounts depend on the purpose, place and method o~ application and on the particular compound. Thus9 where microbial population læ expected to be high, such as in menstrual f'luid, larger amounts preferably are employed. Thus, ~or control of menstrual malodorJ at least about 0.04% by weight of menstrual ~luld ~ deslrable and 0.10% or more is preferred.
Within the broad scope, pre~'erred ranges are hereina~ter disclosed ln the context o~ the particular use and method of application.
The amino acid compound may be applied to the situs : Or formation o~ microblally produced undesirable prod~cts ln various ways. In its use for the inhlbition of ~ormation o~ malodorous materials ln menstrual fluldg th~ amlno acid compound is conven~ently applied to receptacles ~or the *luid such as catamenial dressings or to such other material~
which may receive the fluid such as bed pads~ clo~hingJ etc.
. By "catamenial dressings" is meant sanitary napkinsJ tampons and interlabial pads which usually conslst o~ a core o~ one .~ ~0 or more la~ers o~ highly absorbent, relatively dense materials which have a flu1d permeable~ æoftg knitted, woven or non ~oven wrapper~ The cores are conventionally made ~f layers ;:
o~ fibers such as carded cotton webs~ air-layered cellulosic fiber webs, comminuted wood pulp bats, tissue pulp or like ~5 materials but may be made of newer synthetic mater~als such as synthetic polymer ~oams and fibers. Although the amino :~ ~cid compound may be.distributed uniformly thrDugh the !
-~7~i~S~
PPC 1~5 catamenial dressing, lt is more userul to place ik ln that portion which flrst contacts the body dlscharge, Thus, lt is preferably applied to the surface of the absorbent cores of the dressings or to the covers or both in such a manner that the amlno acid compound is presenk on the sur~aces thereo~ in an amount ranging from about 0.001 g. per square lnch to about 0.1 g. per square inch. Such amounts have been found to pro~ide the desired concentration in terms o~
the amount o~ amino acid compound to total body secretion.
A preferred range ~or catamenial dressings ls from about 0~004 to 0. o6 g . per square inch.
.
The amino acid compounds may be applied to the cata- 7 menial dress1ngs during manufacture or use. When applied during manu~acture, it may be applied by spraying either an aqueous spray or an aerosol spray, pad~ ng, soaklng, or by ..
dustlng or any known method ~or applying materials thereko.
An aerosol spray may employ such propellants as dichloro-di~luoromethane, tri~hlorofluoromethane; a solvent spray may employ substantially inert solvents such as isopropanol.
The use of a propellant or inert organic solvent is preferred over an aqueous solution or suspension to minimize drying o~ the catamenial dressing subsequent to the application of the amino acid compound. In addition~ the amino acid comp~und may be applied to the dress~ngs prior to use in dry powder ~ormulationsc ' ,; .
.~ "
: ' "' ` " ' ~ ' ' ~' '' . , 5~
The application of the amino acid compoun~ may be made topically to the dermal surfaces pre~erably in a suitable carrier such that it is distributed on the dermal surfaces in amounts sufficient to provide at least 0.01% by weight of body secretion as hereinbefore specified. The application preferably is made prior to the secretion of the body fluid to preclude substantially completely the forrnation of the undesirable pro-ducts. However, application may be made subsequent ther~to by minimizing microbial action on the body secretions. Topical applications ~o dermal surfaces are suitable for inhibiting malodor development~ When the application is to be topical, the carrier may be in solid, liquid, spray or semi solid form in cosmetic or pharmaceutical carriers intended for topical use.
Carriers into which the amino acid compound may be incorporated include lotions, ointments, aerosols, water solutions, creams, pulverized mixtures, geI sticks and the like. me various additives and diluents include ointment additives such as poly-sorbate 80, polyoxyethylene sorbitan trioleate; surfactants and emulsifiers such as lauryl sul~ate, sodium cetyl sulfate, glyceryl monostearate, diethylaminoethyl alkyl amide phosphate, isopropyl myristate, octyl alcohol, glyceryl and ylycol esters of stearic acids: glycols such as propylene glycol, other polyhydroxy compounds such as glycerol, sorbitol, alcohols such as ethanol, isopropanol, witch hazel (Hamameli~ water~;
perfumes: essential oils, propellants such as halogenated !
hydrocarbons, e.g., dichlorodi~luoromethane, trichlorofluoro~
ethaneJ etc., carbon dioxide and nitrogen; solid diluents such as calcium carbonate, starch~ bentonite, talc; and silicone-type fluids such as polysiloxane fluid. Selection o~ the particular carrier varie~; with use. In dermal preparations for the control Or inflammatory skin condltions, aqueous compositlons are desirable. Preferred compositions for such applications are khose comprising wikch hazel as a carrier component.
In compositions for topical application, the amino acid compound is employed in an amount of at least 0.05~ by .welght. This is desirable in ~iew of the diluting and possible partial deactivating effect o~ the carrier. The amino acid compound may be present in larger amounts and may even constitute the major portion of the composition although less desirable from practical considerations. For topical application, the amino acid compounds are preferably employed i~ the form o~ alkanolamine salts. When the carrier is aqueous, the salt may be formed in the composition by admixing the free acid and the alkanolamine in the aqueous carrier.
' ` ' . ' , .
~ .
.~' ..
. , .
"'; ~ ' , '.' . . ': :, , 7 ~
PPC 1~5 In preparatiorsfor the control of inrlan~atory skin conditlons, the amino acid compounds employed are preferably in the form of acid or water soluble mono-valent salt or mixtures therelof in an aqueous composition ln an amount of from about ~ to about 15% by weight when based on the weight o~ free ~cid.
When incorporating the amino acid compound into a lotion, cream or aerosol, the amlno acid compound may be added in a solvent compatlble with the system in which it is incorporated such as water~ glycerol~ propylene glycol, tripropylene gl~colJ methyl ether, ethanolJ etc. Alternatively, - ~he amino acid compound may be added to the ~inal composition : and int~mately admixed therewith~ Such would be the pre~erred . method for preparing dusbng powders as well as aqueous ~5 solutions such as in witch hazel.
The compositions abov~ described are applied to the situs o~ production o~ undesirable materlals by the various microorganisms. The ml~roorganisms associated with the production of materials contributing tv menstrual malodor include Gram Negatlve or~anisms such as Proteus mir ebs1ells ~ ~ Aerobacter ~ 5 Escherich~s c~
Pseudomonas ,~eruginosa~ etc. J Gram Positi~e organisms such as s aureus, ~ cc~ faecal _~ etc~ and yeast ~` such as Candida ~ , etc. The mlcroorganlsms associated with the pro~uction of' substances contributing to axll3~ry . ..
!
. . .
~s~
P~C 1~5 malodor are those normally present on the skin surfaces of which those of the genera Cor~nebacte~rium and - , Staphylococcus are the most important. Coryn,ebac-teria are also associated with the production of acids contri-buting to the undesirable in~lammatory condltlons o~ the skin. By employing the compounds and compositions in accordance with the present 'inventlon, the action o~
the microorganisms which results in the production of undesirable acids is somehow inhibited or al~ered, The amino acid compound is believed to be proceeding by removal of the necessary metallic co-factor for the . . .
enzymatic production of fatty acids~ HOwever, the lnven-tlon is not llmited to any particular theory and the preventative control of fatty ac-ld productlon may be ~' 15 achieved without necessaril,y causing detrimental e~fect on microbial ~lora.
The ef~ectiveness of the amino acld compound in inhibiting the formation of undesirable fatty acids from lipids was determined by gas chromatographic analyses and the effectiveness in odor control was determined by organ-'~ ~0 oleptic techniques.
. .
'~ Gas chromatographic analyses employed comparisons with known acids. The method employed was as ~ollows:
., . .
! 16 .~
..... , .. , . .. , ... .. , ., . , ~ ., . ", . " .. .. .
~5~.
PPc L85 Fatty acids extracted in diethyl ether frcm acidified test samples were determined by gas chromatvgraphic procedures using a Hewlett-Packard 76XOA instrument and Porapak ~S 80/100 mesh in a 6 ft. x 2mm. I,D. glass col~n. The instrument was pro grammed from 135 c to an upper limit o~ 235 c at the rate of 4 C temperature rise per minute, holding the upper limit~ for ~ix minutes. Helium was used as a carrier gas at a pre~ure of 60 PSI and a flow rate of 40 ml./m.in.
For ev~luation o~ the ~fectiveness o~ catamenial ; O dressin~s in odor control~ quantitative organoleptic evaluation method was employed referred to as the Modified Ratio Scale Organoleptic Evaluation method as follows, ' , " , The Modified Ratio Scale Organoleptic Evaluation Method -i This method is devised so that data obtalned ~rom an organoleptic appraisal panel may produce an evaluat,ion of a sample characterized as an absolute value ~or odor intensity.
Thus, not only can the dif~erence between two samples o~ an odorant placed in di~erent en~ironments (e~g.g on a pad . -.
w~th and without deodorizer) be detected~ but further, the evaluation will indicate, quantitatively3 as to whether the , ~ odor intensities o~ the ~amples are strong or wealcO For - example, one sample may contain a deodorizer which i5 many tlmes as ef~ectlve as that contained in a second sample~
This notwithstandlng, both deodorizers may only produce a small decrease in the odor intensity, all of which is indicated by the sub~e~t evaluation methodO
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PPC 1~5 The flrst step in this method is to determine the threshold concentration of the odorant, The method used is described by Fred H~ Steiger in Chemlcal Technology, Volume 1, pg, 225, April 1971, wherein the dekerminati.on o~ the odor threshold concentration for ethylamlne is describedJ applying the Weibull distribution ~unction.
Generally~ this procedure requlres the gathe~ing Or organoleptic data from a panel presenked with a series of sa~ples containing odorant in increasing concentrations in order to determine the concentratlon level at which an arbitrary percentage of the paneli~ts can detect the odor.
For the purposes of the current, evaluation that arbitrary percentage is chosen as the cumulative 50% level, As so determined, the threshold concentration o~ the odorant isPspeci~ic to the odorant and the condltions of the sampling procedure.
- The method employed herein ~or panel evaluation is to present each panelist with a series o~ samples, ln a ~ampling apparatus which conslsts of an opaque, one pint~
polyethylene Mason Jar having a pol~ethylene screw cap fitted onto :Lts neck. The ~ar is internally lined with a polyethylene bag and a Buchner funnel is fitted about ~he cap, wlth the narrow outlet portion of the ~unnel, below the ~ilter plate of the funnel, extending through the cap and into the llned jar. A sample is placed in the jar, the Jar is capped wit,h the Buchner funnel fitted in place and a watch glass is placed across the wide inlet portion o~ the funnel.
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PPC 1~5 The sample is then allowed to equilibrate for one hour at ambient conditions. For the purpose o~ the threshold determination, the samples each comprise a specific concentration of the odorant in a water solution, a total o~ 3 ml. o~ solution being placed in the jar. A panel o~
about 30 women are presented with a series Or equilibrated samples o~ increasing concentration and, start~ng with a sample at zero concentration (water only), are asked to report the ~irst sample having a detectable odor. The panellsts are instructed to snif~ each sample in turn, pausing 30 seconds between samplings. The accumulated data is organized to establish the cumulative percentage of the panel which detects an odor at each concentration level correspondlng to each sampleO The data7 ~o organized, is plotted as described in the a~orementioned Steiger article on Weibull Probability Paper with the concentrakion as the abscissa and the cumulative percentage of the panel as the ordinate. The concentratlon ak 50~ is then taken as the threshold concentrationD
~0 Havlng established the threshold value, the ~odified Ratio Scale Method is applled by preparing a master curve.
Using the same testin~ apparatusJ a series of samples are prepared and presented to the panel wherein the concentra-tlons o~ odorant can be expressed as multiples of the threshold concentration or odor unlts. One of these samples is 20 t~mes the threshold concentration (20 odor units)O
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PPC 1~35 In accordance with the standard method of Ratio Scaling, each panelist is asked to evaluate the set of samples berore her and to assign a value to the odor inten-slty of each sample in proportion to the intensity of the other samples, The panelists are ~ree to choose whatever scale they wish. For exampleg a panelist may ~ssign 10 to the strongest sample. A sample having half that i.ntensity~
in accordance with this panelist's evaluatlon, would then be assigned a value o~ 5. The accumulated data then consists Or a series of evaluations ~or each panellst, each serles being bas~d upon the individual panelists' scale. Arbi-trarily~ a ratio scale value of 100 is assigned to the sample concentration of 20 times threshold concentration. Each of the panelists' evaluations are then proportioned to bring their individual scales to the basis of 100 for 20 times threshold concentration. For ex~nple, the evaluations of a panelist assigning a value of 10 to a firsk sample having a concentration o~ 20 times threshold concentratlon will be proportioned to show, for that panelist~ a value of 100 ror the flrst sample and a ~alue o~ 50 ~or tile second sample.
me data is now organized so that, ~or each sample corres-ponding to a specific multiple of the threshold concentration, there is a series o~ Ratio Values, all on the same scale (20 timPs Threshold Concentration -- 100) corresponding to each panelist's evaluation o~ this sampleO The geometric means o~ the ratio values for each sample is calculated and that value is taken as the Ratio Value for that multiple of threshold concentration.
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When the log of the Ratio Value is plotted, as the ordinate, against the lo~ o~ the multiple of threshold concentration, a straight line, ~itted to the data points between 3 to 20 times threshold concentration gives an excellent correlation.
It has been discove~ed that irrespective of which amine odorankis testedJ when a threshold concentratlon is determined ~or that specific odorantand the method ~ constructing a Master Cur~e as described above is followed, the resultlng Master Curves are superimposable between multiples of thres~
hold concentration of about 3 to about 20.
, The curve obtalned ln this way ~or isobutyric acid, a chemically dissimilar material also was superimposable on the Master Curves *or the amines. Thus, the reference odorant in any test may be chemically dissimilar to the odor constltuent or constituents belng tested. ~~
The Master Curve may now be used to evaluate the odor intensity of any odorant when placed in any environment such as, for example, on a pad of untre,,-~ted cellulosic ~ibers or :
on a pad of ~ibers containing deodorizing material and, in addi~ion to obtaining comparisons between the relative inten-sity o~ the samples tested, an absolute measure of the intensity o~ each samp:Le may be obtained. To do this, the p~nel is presented with a series o~ samples, one of which is a standard sample consisting o~ known concentrat~on o~ the odorant being tested in an enYironment identical to that . ' ~1 ": . ~ , .
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PPC 1~35 used in producing the Master Curve~ Preferably, this standard sample is chosen as having 20 times the threshold concentration arld hence, a Ratio Value of 100 on the Master Curve.
The panelists are again asked to evaluate the series of samples usln~ whatever scale they choose. ~ased on the value which each panellst gives to the intensity of the standard sample, all other values given by the paneli.sts are proportioned so as to be consistent with the rating Or the standard sample, e.g.~ a panelist asslgning a value of 50 to the standard sample and 5 to a second sample of ~ unknown intensity will have these values proportioned so the standard will be given a Ratio Value of 100 and the unknown sample given a Ratio Value of 10. By referring to the Master Curve, lt can be determined that the panelists now proportioned Ratio Value of 10 for the ~,econd sample is equivalent to an odor intensity of a certain number of multiple~ o~ threshold concentration as read ~rom the Master Curve were 1.2, the odor intensity o~ the s~mple of unknown intensity, in the test environment, is the same as a sample having an odorant concentration o~ 1.2 times the threshold concentration in the standard environment.
Prel.iminary determinations were made in connection with the menstrual malodor aspect o~ the present invention to establish the presence of phospholipids in menstrual ~luid and to establish malodorous fatty acid production by microbial flora commonly present in menstrual fluid~
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The presence of s~gnificant amounts of phosphollpids in menstrual fluid was established by a procedure consisting of heating the phospholipids with perchloric acid to oxidize the organic portion of the molecule and convert the phosphorus to a blue phosphomolybdate which may be read colorimetrically as more fully described on pp. 375-376 o~ "Bray's Clinical Laboratory Methods" by Bauer et al, 17th Edition, C. W. Mosby Co., 1969. Ten samples of menstrual fluld were collected in cups and subJected to phospholipid analyse~ The analyses established the presence o~ ~rom 2250 to 4140 ppm of phospho lipids amounting to ~rom 0.225 to 0.4% of the fluid.
To establish the ability of microorganisms commonly present in menstrual ~luld to produce malodorous fatty acids, separate samples of sterile human blood were inoculated with dir~erent organisms previously lsolated from menstrual fluid, f~llowed by incubation and analysis by gas chromatogr~phy as hereina~tar described. In the determination~ blood was employed in~tead of menstrual fluid because o~ ~he avaiLability of sterlle blood and the desirability of a sterile substrate to identi~y ~atty acid production as being caused by the organism used ln lnoculation, The suitability o~ substituting blood was based on the known fact of the presenee of triglycerides in both blood and men~trual fluld and on pre~iminary experi- -ment~ on ~ix samples e~ch of human blood and menstrual fluid which showed average total phospholipids to be 2807 ppm and 2771 ppm respectively. The methods employed and the resul~s obtained were as follows:
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2~5 ml. test samples of sterile whole human blood were separately inoculated with a 0.2 ml. bacterial cell suspension of various test organisms previously isolated by conventional methods from menstrual fluido The test samples as well as an un~inocula~ed control sample were incubated at 3~C. ror 24 hours in a constant tempexature bath with constant shaking at 200 r.p.m. Thereafter, all samples were subjected to gas chromatographic analyses, The results are seen in Table A.
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TABLE A
Iso-butyric Butyric Iso-valeric Unihoculated Control 0 0 - 3~5 Gram Negative Bacteria Proteus mirabllis ~9.5 9 111.7 Klebsiella ~ 0 0 11.3 a~ F~F~ aerogenes 0 8.7 15~0 ; ~ ~scherichi-a coI~i~~ 0 0 0 Pseudomonas~ aeru~inosa 0 0 0 Gram Positive Bacteria . .. .. ...
Staphylococcus aureus 1307 0 50,5 Cbco~~ ~~raecalis O o 39 1 . . _ _ O
) Yeast : i ~ Candida albicans 12 0 38-$
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The ~ollowing examples illustrate the various aspects of tAe present invention but are not to be construed as limiting:
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PPC 1~5 ~XAMPLE I
Two menstrual fluid saoples were ccllected a.nd analyses were rnade initlally f'or ~atty acids: isobutyrl~, : butyric and isovaleric by gas chromatography on untreated, unincubated fluid. The~eafter, te~t samples o~ about 2 ml.
of ehch menstrual ~luid were preparedO Two sets, each set containing twv di~ferent samples o~ menstrual fluid ~Jere treated as follows: to one set~ disodlum ethylenediaminete-traacetate was added to provide a flnal concentration thereof of 0.2~ by weight of menstrual fluid and the other set was le~t untreated. Both treated and untreated samples were incubated at 37C. for 24 hours and thereafter analyzed by gas chromatography for the fatt,y acids previously named.
The results are seen in Table I~
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: TABLE I
~ATTY ACIDS (ppm~
~: ~ ~ Isovaleric Sample 1 Freshly Obtalned Unlncubated, Un-treated Control 0 36 0 .
Incubated ~` Untreated 685.7 1014.0 857.1 Incubated Na2EDTA Treated 0 1606 14.3 Sample 2 Freshly Obtained -: Un~ncubated Untreated Control O O O
Incubated Untreated 475.0 307.0 336.o Incubated .
Na2EDTA Treated 4.0 13.0 9.0 .~ .
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EXAMPLE II
Five samples of 2.5 ml. o~ sterile human blood were inoculated with 0.2 ml. of Proteus mirsbilis suspension.
To ~our of the samples, dlsodium ethylenedi~minetetraacetate was added to supply amounts ranging from 0.04% ko 0.2%.
O~e sample was an inoculated control containing no ED'M
compound. In addition/ an uninoculated control sample ~ras prepared o~ 2.5 ml. Or the blood ko whlch 0.2 ml. Or sterile distilled water was added. The treated and untreated inoculated sampl~s and ~n uninoculated control sample were .0 then lncubated ~or 24 hours at 37C. in a constant tempera-ture water bath with shaking at 200 r.p.m. At the end of : th~s period aliquots were tested for th~ presence of the acids by gas chromatography. The results are given in Table II~
, TABLE II
IREATMENT ~ Acids_(~pm~
N~2EDTA .IsobutyricIsovaleric .
Proteus ~ No Na2 EDTA 102.7 98.2 Proteus ~ 0.04~ Na2 EDTA 28.4 52.3 : Proteus ~ 0.1% Na2 EDTA 6.6 17.5 Proteus -~ 0.2% Na2EDTA 7.9 17.6 ; Untreated Sterile Blood 0 0 :'. :
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PPC 1~5 . EXAMPLE III
Sterile blood inoculated with Proteus mirabilis was placed on treated and un1;reated samples o~ fluf~ pads and sanitary napkins~ To pre~pare treated samples, a 14 percent aqueous solution of a blend of disodium and tetrasodium ethylenediaminetetraacetate (pE~ 7) first was applied at various positions and concentratlons to samples of rlu~f pads or samples of sanitary napkins by soaking, spraying or padding on th0 cover. ~lhe samples were there~
~: a~ter dried and the amount of the ethylenediaminetetraacetate salts dispersed in the samples determined by weighing.
Blood previously inoculated wlth Proteus mirabilis was .. . .
added to the ~arious treated samples as well aæ.to an untreated sample and to a dimethylamine reference odorant sample. ~Three milliliters were used for fluf~ pads and :~
fiYe milliliters were used for the sanltary napklns)~
The samples khen were incubated at 37C ~or '24 hours and therea~ter sub~ected to organoleptic tesking ln the msnner previously descrlbed. The results showing signi~icant odor reduction are ~een ln Table III~
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ppt~ 1~5 XAMPI ~ I
In an experlmen~ carried ou~ over a perlod o~ ~Ix month~, a panel of s~ven ~ub3ect~ wore ~nitary napklns menstrually for a minimum of four hours or un~ he dis-charge o menstrual fluld wa~ such that a ehange o napkin 5 ~aR neces~ary. Within thirty mirlu~ces ater removal, the napkins were inspected and physica:L da~a suoh as weight, physical appearance and stain area were recordetl. There-~fter, the napkins were incubated at 30C. for one hour and thereafter evalua~ed for odor.
Thls procedure was r~peated by each panelis~ ~ith a txea~ed and untreated (con~rol) napkins but on alter-nate month3. In ~om¢ ea~es, the da~ca was collec~ed over the etltire six^month period while in other cases, the data was only for two mo~ths or for four months. The 15 ~election of product to ~ E~iven panelist was rando~zed .
80 that factors such a~ climate or activity changes would have minimum influence.
me 'created napkir~s employed had be~n prepa~eed by ~~
re~oving the ~on-woven fabric cover o a MûD~SS* Sanitary 20 Napkin, passing the abæorbent ti~sue ir~ner padding through a solu~ion of a bl~nd o~ disotlilm~ and tetrasodium ethylerle-diaminetetraacel:ate (prepared as described in Exa~ple III), drying and replacing ila t~e 1u~d perviou~ eover. T~e cor~-centxation of the ~alt ater drying was 0.004 gr~m per ~5 square inch of f-abric.
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The odor data from all sub~ects for this period were pooled and the odor intensity responses for test products compared wlth a control~ The odor response for twenty fi~e treated and twenty-~ive untreated napkins were described in odor units of from zero to 21 (m~ximum). The untreated napkins had odor unlts ranging from 3 to 21 wlth rive napkins above 15. Ten o~ the treated napkins had odor unlts Or less than 3 and none above 11 EXAMPLE V
Two milliliter portlons o~ dilute human plasma (1 part of plasma to 2 parts of sterile distilled wat~r) were i~oculated with ~ eb~cter~w . To three of the samples, disodium ethylenediaminetetraacetate was added to produce a concentration thereo~ of 0~ 0.2% and 0.5~.
One sample containing no sodium ethylenediamlnetetraacetate . served as an untreated control. Xn addition, an uninocu-lated control sample of unmodified dilute human plasma was prepared. The teæt and control samples were incubated at 37C. wlth shaking at approximately 200 r.p.m. ~or 24 hours.
At the end of this ~eriod, the samples were tested for ~ree fatty acids by gas chromatography. The results obtained were ~s ro110ws:
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~5~1 Sl TABLE IV
Treatment Fatky Acids (ppr~
Iso ~ Isovaleri __ _ Untreated sterile plasma 0 Corynebacterium Inoculum -No Na2EDTA 155 56~
Corynebacterium Inoculum 12 22 - + 0.5% Na2EDT~
Corynebacterium Inoculum 25 49 0.2~ Na2EDTA
Corynebacterium Inoculum 22 41 0.1~ Na2EDTA
. . ~ EXAMP~E VI
. Disodium ethylenediaminetetraacetate was added to a two milliliter portion o~ a brain-heart in~usion (BHI) broth containing natural axillary flora conslstlng primarily of Corynebacterium and ~5~ 1nocccu~ to produce a ~inal concentration of 0.5~ by weight. A second two milliliter portion o~ inoculated broth contained no disodium ethylenediaminetetraacetate. In addition~ a two milliliter portion of sterile BHI broth served a~ an uninoculated ~ontrol. The test and control samples were incubated at . 37C with shaking at 200 r.p.m. ~or 24 hours~ At the end ; ~0 o~ thls periodg samples were determined for free fatty acids by gas chromatQgraphy~ m e results are seen in T~bl~ V.
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PPC 1~5 TABLE V
Treatment F'A~t~ Aci~ D
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Isobutyric Isovaleric __ _____ Sterile BHI O O
BHI inoculated with underarm culture 32 57 BHI inoculated with -underarm culture + 0-5~ Na2EDTA O o .
EXAMPLE VII
An aqueous solution containing 0~45 percent by weight o~ a mixture Na2EDTA and Nal~EDTA (prepared as described in Exo III) was applied to one axilla of a test sub~ect by means o~ a sterile guaze pad which had been wetted with the solu-tion. Sterile distilled water was applied in a similar manner to the other axilla and served as the untreated controlO Both axilla were evaluated by ol~actory sensing twice daily to determine compartiYe odor development and intensity. The treated axilla exhibited a substantial deodorant effect.
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EXAMPLE VIII
_ _ _ A cream suitable ~or application to the ~od~ for . inflammatory disorders of the skin is prepared by (1) heating Part A (below) ~o 70 t2) Part B ~below) to 75C~ (3) adding Part B to Part A with agitation and (4) adJ'usting the pH to 505 with dilute sodium hydroxide.
Part A
Cetyl alcohol 2.5 : Stearyl alcohol 5,0 Isopropyl myristate 2,0 Light silicone oil 1.0 "Emplex'l Methyl paraben2 0,15 Propyl paraben3 0~05 ,`' ~"' ~ Part B
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Delonized water 7~o8 Disodium salt of EDTA 4.0 Propylene glycol 500 , . --- .
lSodium salt of reaction product of lactic and stearic ; acid tPatcv Products~ Kansas City, Missouri) - Trademark . .
Methyl hydroxybenzoate- Trademark --3Propyl hydroxybenzoate - Trademark ;:
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EXAMPLE IX
A lotion ~uitable as a skin lotion is prepared by ~1) heating Part A (below) to 7~C, (2) Part B (below) to 75C t3) adding Part B to Part A with agitatlon and (4) ad~usting khe pH to 5.3 with dilute sodium hydroxide.
' Par~ A
Cetyl alcohol 1.9 Stearyl alcohol 3~0 Isoprop~l myristat~ 1~3 I~ght silicone oil o.8 "Efflplex" 1.1 10 . ~ Methyl paraben 0.15 . Propyl paraben ~ 0.05 : , ., . -Part B
Deionized water 81.7 Propylene glycol 300 _-Dlsodium ~alt o~ EDT~ 7.0 . :
EXAMPLE X
;; 15 The compositions descrlbed in Examples VIII and IX
: may be ~pplied to dermal sur~aces to reduce ~ormation o~
tty acids by the act:ion of Corynebacterium species o~
exuded sebum, said ~atty acids b~ng unde~irable in ln~lammatory skin dlsordersO
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. EXAMPLE Xl .. . .. _ . A hand and body lotion suitable f'or ~nalo~or control is prepared by (1) heating Part A (belo~r) to 82~C, (2) heating Part B ~belsw) to 78C, (3) adding Part A to P~rt B wlth stirring and (4) coollng to 46C and addin~
Part C.
Part A ~ Wei~t Mineral Oil 3,oo Glyceryl monostearate 5.00 ~sopropyl palmit~te 3.00 ' Amerchol-H-91 1. 00 Stearic acid 1.50 ~, Propyl paraben 0.05 :
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Methyl paraben 0.15 Onyxide 5002 0.20 Propylene glycol - VSP 4,00 Glycerine 96% - USP 3.00 Standapol SHC-3013 2~50 ~ Disodium salt of EDTA 5.00 :~ Deionlzed water 71.35 , . . . .
part C
Fragra.nce 0.25 Sterolatum (Amerchol Products~ Inc. 3 - Trademark 2 2-Bromo-2-nitropropane-193-diol (onYx CoO)- Trademark ~: 3 Sulfosuccinate hal~ ester tHen~el Co-) _ Trademark ;~ !
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PPC 1~5 EXAMPLE XII
A body powder suitable for topical application is ~repared by thoroughly mixing the followlng:
Trisodium ethylenedlaminetetra~cetate 10 g~
Talc 787 g.
Fr~grancei . 3 g.
EXAMPLE XIXI
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The composition described in ~xample XII may be applied to dermal surfaces to inhibit formation o~
malodorous fatty acids by the acitioni of ~JoryAebac~er~un . species on exuded sebum.
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EXAMPLE XIV
A sanitary napkin is prepared ha~in~ an absorbent core o~ commiinuted wood pulp and a non~oven porous cover~
and having on the upper surface of the wood pulp core ~odium nitrilotrlacetate in an amount of loO milligram per ~quare inch of surface area. In ltæ preparatlon, the nltrllotriacetate iæ applied to the absorbent core in dry state li`rom an aerosol spray employing dichlorodi~luoro-:, methane as a propellant after wh~ch the nonwoven cover is placed aro~md the core.
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PPC 1~5 ' ' ~
A ~anltary napkin similar to th~t de~cribed ln ~xample XIV except ~hat bokh~ the upper sur~ace o~ th~
~ood pulp core and the ~luld perYlous coYer ha~ ~pplied ~ho~eto sodlum N-hydroxyethylethylenediamlnetrlacet~
~EDT~ ~lt) at ~ rate o~ ~o6 mg~ per ~qu~r~ inch o~
surrace are~.
EXAI~Pl:E XV~
A catamenlal tampon i8 prepaxed having ~n ~- absorbent compre~e~, cylindrlcal core o~ tl~#ue pulp ~ nd ~hort ~ayo~ ~ibers~ The leading one-hal~ o~ th~
. ~urface o~ the cor~ h~s applled thereto 1~5 mgO per ~quar~ lnch o~ a neut~al blend o~ di- and tetra~odium ethyl~nedlamlnetetraacetate. The ~alt iæ applied to the cox~ ~ur~ace in a dry state fro~ an aerosol .~pray a~ployln~ d~chlorodirluoromethane propel~antO A nonwov~n ~5 co~er i~ wr~pped axound the core and ~ wlthdrawal ~tring otte~ around the core at its tr~llqng endO
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, ~ catamenial tampon ~imllar to that de~cribe~ ~n : ~xample XVI but whereln the l~ading two thiPds sur~ace o~
~oth the ab~30r~ent core and ~luid per~iou~ cover h~v~
~ppIl~d thereto 1.0 mg. ~er square inch o~ tri~od~u~
~thylenedi~nine tetra~cet~te~
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PPC 1~5 EXAMPLE XVIII
A cream stick was prepared by admixin~ at about 60C the ~ollowing materials in the indicated proportion~:
Wei ght ln ~ ~:rams Ozokerite wax ~ 48.o Car~auba wax 32.0 Candellila wax 64 ~ 0 Emcol 249~3K1 42 . o Tenox 42 0 . 8 Benton M-203 8090 Talc 120. 0 Propyl paraben o.8 Neutral blen~ of Na2EDTA 40. 0 plus Na4EDTA
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1 Alkoxylated alcohol (Witco Chemical Company) ~ Trademark 20~ Butylated hydroxy anisole~ 20~ butyla,ted hydroxy toluene, 60% corn oil (Eastman Chemical Products Inc.) Trademark ~ . .
', J Modi~ied bentoni~e (National Lead Compan;,~) _ Tradema.rk Prepared as described in the Footnote 5 ~o Table III.
~, Therea~ter the mixture was poured inko chilled molds to provide a final product in chilled stick form.
~0 Test panelists were provided with two coded cream stlcks ~or axillary deodorant use, one stick being of the above composition and the other stick of similar composition but not containing the blend of the two sodium ethylene-. . .
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TABLE A
Iso-butyric Butyric Iso-valeric Unihoculated Control 0 0 - 3~5 Gram Negative Bacteria Proteus mirabllis ~9.5 9 111.7 Klebsiella ~ 0 0 11.3 a~ F~F~ aerogenes 0 8.7 15~0 ; ~ ~scherichi-a coI~i~~ 0 0 0 Pseudomonas~ aeru~inosa 0 0 0 Gram Positive Bacteria . .. .. ...
Staphylococcus aureus 1307 0 50,5 Cbco~~ ~~raecalis O o 39 1 . . _ _ O
) Yeast : i ~ Candida albicans 12 0 38-$
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The ~ollowing examples illustrate the various aspects of tAe present invention but are not to be construed as limiting:
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PPC 1~5 ~XAMPLE I
Two menstrual fluid saoples were ccllected a.nd analyses were rnade initlally f'or ~atty acids: isobutyrl~, : butyric and isovaleric by gas chromatography on untreated, unincubated fluid. The~eafter, te~t samples o~ about 2 ml.
of ehch menstrual ~luid were preparedO Two sets, each set containing twv di~ferent samples o~ menstrual fluid ~Jere treated as follows: to one set~ disodlum ethylenediaminete-traacetate was added to provide a flnal concentration thereof of 0.2~ by weight of menstrual fluid and the other set was le~t untreated. Both treated and untreated samples were incubated at 37C. for 24 hours and thereafter analyzed by gas chromatography for the fatt,y acids previously named.
The results are seen in Table I~
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: TABLE I
~ATTY ACIDS (ppm~
~: ~ ~ Isovaleric Sample 1 Freshly Obtalned Unlncubated, Un-treated Control 0 36 0 .
Incubated ~` Untreated 685.7 1014.0 857.1 Incubated Na2EDTA Treated 0 1606 14.3 Sample 2 Freshly Obtained -: Un~ncubated Untreated Control O O O
Incubated Untreated 475.0 307.0 336.o Incubated .
Na2EDTA Treated 4.0 13.0 9.0 .~ .
.
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EXAMPLE II
Five samples of 2.5 ml. o~ sterile human blood were inoculated with 0.2 ml. of Proteus mirsbilis suspension.
To ~our of the samples, dlsodium ethylenedi~minetetraacetate was added to supply amounts ranging from 0.04% ko 0.2%.
O~e sample was an inoculated control containing no ED'M
compound. In addition/ an uninoculated control sample ~ras prepared o~ 2.5 ml. Or the blood ko whlch 0.2 ml. Or sterile distilled water was added. The treated and untreated inoculated sampl~s and ~n uninoculated control sample were .0 then lncubated ~or 24 hours at 37C. in a constant tempera-ture water bath with shaking at 200 r.p.m. At the end of : th~s period aliquots were tested for th~ presence of the acids by gas chromatography. The results are given in Table II~
, TABLE II
IREATMENT ~ Acids_(~pm~
N~2EDTA .IsobutyricIsovaleric .
Proteus ~ No Na2 EDTA 102.7 98.2 Proteus ~ 0.04~ Na2 EDTA 28.4 52.3 : Proteus ~ 0.1% Na2 EDTA 6.6 17.5 Proteus -~ 0.2% Na2EDTA 7.9 17.6 ; Untreated Sterile Blood 0 0 :'. :
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PPC 1~5 . EXAMPLE III
Sterile blood inoculated with Proteus mirabilis was placed on treated and un1;reated samples o~ fluf~ pads and sanitary napkins~ To pre~pare treated samples, a 14 percent aqueous solution of a blend of disodium and tetrasodium ethylenediaminetetraacetate (pE~ 7) first was applied at various positions and concentratlons to samples of rlu~f pads or samples of sanitary napkins by soaking, spraying or padding on th0 cover. ~lhe samples were there~
~: a~ter dried and the amount of the ethylenediaminetetraacetate salts dispersed in the samples determined by weighing.
Blood previously inoculated wlth Proteus mirabilis was .. . .
added to the ~arious treated samples as well aæ.to an untreated sample and to a dimethylamine reference odorant sample. ~Three milliliters were used for fluf~ pads and :~
fiYe milliliters were used for the sanltary napklns)~
The samples khen were incubated at 37C ~or '24 hours and therea~ter sub~ected to organoleptic tesking ln the msnner previously descrlbed. The results showing signi~icant odor reduction are ~een ln Table III~
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t~ S~i3 . bD n3 n3 u ~d q~ ~' P ~ ~1 P ~1 ~1 ~ ~--~ 4t ~ O a) (U ~ n3 rt H r~l 4~ I ~ LS~ I g ~ rl ~ t3~ n3 ~i ~
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a3 ~ C ~ ~ ~rl ~ rl l ~r p C P~ I ~O I I ~ C ~ ~ W
O a3 0 ~ ~ u~ u~ O S ~ ~ ~ r-l 1 S ~ ~rl H ~r O ~ r~ ~ aO ~ ~33 '13 H~ :~ O d ~ O ~ u~,t ~,J a ~,~ H ~ O r~t ~ ~¢ r~ 3 ~; ~ a,q-' qt ~t ~~ r~ ~ ' a3 S~
~:. Lu ~ nn3 O ~ 4 h O ~ uO a O ~ ~rl ~ 5 : ~a ~ a) ~ ~LU ~ 5~-r O ~ ~: ~ c3 rdR~ a30 ~: r~
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rl ~ ~ bD rH ~ t S~ U
S ~ IH LU ~ ~ rlO ~O ~ r ~: ~4 ~ ~ S
X
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a' n3 ~ cd ~ r~ o H
E~ bD ~ r~ U~ rn ~ O C) 9 0 ~) ~ JI
O O O O C) O O O O r l C~ ~ Lr~
O S~ ~t " ~ bD O
ppt~ 1~5 XAMPI ~ I
In an experlmen~ carried ou~ over a perlod o~ ~Ix month~, a panel of s~ven ~ub3ect~ wore ~nitary napklns menstrually for a minimum of four hours or un~ he dis-charge o menstrual fluld wa~ such that a ehange o napkin 5 ~aR neces~ary. Within thirty mirlu~ces ater removal, the napkins were inspected and physica:L da~a suoh as weight, physical appearance and stain area were recordetl. There-~fter, the napkins were incubated at 30C. for one hour and thereafter evalua~ed for odor.
Thls procedure was r~peated by each panelis~ ~ith a txea~ed and untreated (con~rol) napkins but on alter-nate month3. In ~om¢ ea~es, the da~ca was collec~ed over the etltire six^month period while in other cases, the data was only for two mo~ths or for four months. The 15 ~election of product to ~ E~iven panelist was rando~zed .
80 that factors such a~ climate or activity changes would have minimum influence.
me 'created napkir~s employed had be~n prepa~eed by ~~
re~oving the ~on-woven fabric cover o a MûD~SS* Sanitary 20 Napkin, passing the abæorbent ti~sue ir~ner padding through a solu~ion of a bl~nd o~ disotlilm~ and tetrasodium ethylerle-diaminetetraacel:ate (prepared as described in Exa~ple III), drying and replacing ila t~e 1u~d perviou~ eover. T~e cor~-centxation of the ~alt ater drying was 0.004 gr~m per ~5 square inch of f-abric.
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;~ , . .. ' . ' * ~rademark of ~OHNSI:)N & JOHNSON
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The odor data from all sub~ects for this period were pooled and the odor intensity responses for test products compared wlth a control~ The odor response for twenty fi~e treated and twenty-~ive untreated napkins were described in odor units of from zero to 21 (m~ximum). The untreated napkins had odor unlts ranging from 3 to 21 wlth rive napkins above 15. Ten o~ the treated napkins had odor unlts Or less than 3 and none above 11 EXAMPLE V
Two milliliter portlons o~ dilute human plasma (1 part of plasma to 2 parts of sterile distilled wat~r) were i~oculated with ~ eb~cter~w . To three of the samples, disodium ethylenediaminetetraacetate was added to produce a concentration thereo~ of 0~ 0.2% and 0.5~.
One sample containing no sodium ethylenediamlnetetraacetate . served as an untreated control. Xn addition, an uninocu-lated control sample of unmodified dilute human plasma was prepared. The teæt and control samples were incubated at 37C. wlth shaking at approximately 200 r.p.m. ~or 24 hours.
At the end of this ~eriod, the samples were tested for ~ree fatty acids by gas chromatography. The results obtained were ~s ro110ws:
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~5~1 Sl TABLE IV
Treatment Fatky Acids (ppr~
Iso ~ Isovaleri __ _ Untreated sterile plasma 0 Corynebacterium Inoculum -No Na2EDTA 155 56~
Corynebacterium Inoculum 12 22 - + 0.5% Na2EDT~
Corynebacterium Inoculum 25 49 0.2~ Na2EDTA
Corynebacterium Inoculum 22 41 0.1~ Na2EDTA
. . ~ EXAMP~E VI
. Disodium ethylenediaminetetraacetate was added to a two milliliter portion o~ a brain-heart in~usion (BHI) broth containing natural axillary flora conslstlng primarily of Corynebacterium and ~5~ 1nocccu~ to produce a ~inal concentration of 0.5~ by weight. A second two milliliter portion o~ inoculated broth contained no disodium ethylenediaminetetraacetate. In addition~ a two milliliter portion of sterile BHI broth served a~ an uninoculated ~ontrol. The test and control samples were incubated at . 37C with shaking at 200 r.p.m. ~or 24 hours~ At the end ; ~0 o~ thls periodg samples were determined for free fatty acids by gas chromatQgraphy~ m e results are seen in T~bl~ V.
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: ! 31 .. . . . . . .. .
~L~753~S~
PPC 1~5 TABLE V
Treatment F'A~t~ Aci~ D
~ ~ . _ . .
Isobutyric Isovaleric __ _____ Sterile BHI O O
BHI inoculated with underarm culture 32 57 BHI inoculated with -underarm culture + 0-5~ Na2EDTA O o .
EXAMPLE VII
An aqueous solution containing 0~45 percent by weight o~ a mixture Na2EDTA and Nal~EDTA (prepared as described in Exo III) was applied to one axilla of a test sub~ect by means o~ a sterile guaze pad which had been wetted with the solu-tion. Sterile distilled water was applied in a similar manner to the other axilla and served as the untreated controlO Both axilla were evaluated by ol~actory sensing twice daily to determine compartiYe odor development and intensity. The treated axilla exhibited a substantial deodorant effect.
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EXAMPLE VIII
_ _ _ A cream suitable ~or application to the ~od~ for . inflammatory disorders of the skin is prepared by (1) heating Part A (below) ~o 70 t2) Part B ~below) to 75C~ (3) adding Part B to Part A with agitation and (4) adJ'usting the pH to 505 with dilute sodium hydroxide.
Part A
Cetyl alcohol 2.5 : Stearyl alcohol 5,0 Isopropyl myristate 2,0 Light silicone oil 1.0 "Emplex'l Methyl paraben2 0,15 Propyl paraben3 0~05 ,`' ~"' ~ Part B
.
Delonized water 7~o8 Disodium salt of EDTA 4.0 Propylene glycol 500 , . --- .
lSodium salt of reaction product of lactic and stearic ; acid tPatcv Products~ Kansas City, Missouri) - Trademark . .
Methyl hydroxybenzoate- Trademark --3Propyl hydroxybenzoate - Trademark ;:
: - 33 , : . .
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EXAMPLE IX
A lotion ~uitable as a skin lotion is prepared by ~1) heating Part A (below) to 7~C, (2) Part B (below) to 75C t3) adding Part B to Part A with agitatlon and (4) ad~usting khe pH to 5.3 with dilute sodium hydroxide.
' Par~ A
Cetyl alcohol 1.9 Stearyl alcohol 3~0 Isoprop~l myristat~ 1~3 I~ght silicone oil o.8 "Efflplex" 1.1 10 . ~ Methyl paraben 0.15 . Propyl paraben ~ 0.05 : , ., . -Part B
Deionized water 81.7 Propylene glycol 300 _-Dlsodium ~alt o~ EDT~ 7.0 . :
EXAMPLE X
;; 15 The compositions descrlbed in Examples VIII and IX
: may be ~pplied to dermal sur~aces to reduce ~ormation o~
tty acids by the act:ion of Corynebacterium species o~
exuded sebum, said ~atty acids b~ng unde~irable in ln~lammatory skin dlsordersO
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5~
. EXAMPLE Xl .. . .. _ . A hand and body lotion suitable f'or ~nalo~or control is prepared by (1) heating Part A (belo~r) to 82~C, (2) heating Part B ~belsw) to 78C, (3) adding Part A to P~rt B wlth stirring and (4) coollng to 46C and addin~
Part C.
Part A ~ Wei~t Mineral Oil 3,oo Glyceryl monostearate 5.00 ~sopropyl palmit~te 3.00 ' Amerchol-H-91 1. 00 Stearic acid 1.50 ~, Propyl paraben 0.05 :
;'.' .
` Part B
Methyl paraben 0.15 Onyxide 5002 0.20 Propylene glycol - VSP 4,00 Glycerine 96% - USP 3.00 Standapol SHC-3013 2~50 ~ Disodium salt of EDTA 5.00 :~ Deionlzed water 71.35 , . . . .
part C
Fragra.nce 0.25 Sterolatum (Amerchol Products~ Inc. 3 - Trademark 2 2-Bromo-2-nitropropane-193-diol (onYx CoO)- Trademark ~: 3 Sulfosuccinate hal~ ester tHen~el Co-) _ Trademark ;~ !
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PPC 1~5 EXAMPLE XII
A body powder suitable for topical application is ~repared by thoroughly mixing the followlng:
Trisodium ethylenedlaminetetra~cetate 10 g~
Talc 787 g.
Fr~grancei . 3 g.
EXAMPLE XIXI
.
The composition described in ~xample XII may be applied to dermal surfaces to inhibit formation o~
malodorous fatty acids by the acitioni of ~JoryAebac~er~un . species on exuded sebum.
.~
EXAMPLE XIV
A sanitary napkin is prepared ha~in~ an absorbent core o~ commiinuted wood pulp and a non~oven porous cover~
and having on the upper surface of the wood pulp core ~odium nitrilotrlacetate in an amount of loO milligram per ~quare inch of surface area. In ltæ preparatlon, the nltrllotriacetate iæ applied to the absorbent core in dry state li`rom an aerosol spray employing dichlorodi~luoro-:, methane as a propellant after wh~ch the nonwoven cover is placed aro~md the core.
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PPC 1~5 ' ' ~
A ~anltary napkin similar to th~t de~cribed ln ~xample XIV except ~hat bokh~ the upper sur~ace o~ th~
~ood pulp core and the ~luld perYlous coYer ha~ ~pplied ~ho~eto sodlum N-hydroxyethylethylenediamlnetrlacet~
~EDT~ ~lt) at ~ rate o~ ~o6 mg~ per ~qu~r~ inch o~
surrace are~.
EXAI~Pl:E XV~
A catamenlal tampon i8 prepaxed having ~n ~- absorbent compre~e~, cylindrlcal core o~ tl~#ue pulp ~ nd ~hort ~ayo~ ~ibers~ The leading one-hal~ o~ th~
. ~urface o~ the cor~ h~s applled thereto 1~5 mgO per ~quar~ lnch o~ a neut~al blend o~ di- and tetra~odium ethyl~nedlamlnetetraacetate. The ~alt iæ applied to the cox~ ~ur~ace in a dry state fro~ an aerosol .~pray a~ployln~ d~chlorodirluoromethane propel~antO A nonwov~n ~5 co~er i~ wr~pped axound the core and ~ wlthdrawal ~tring otte~ around the core at its tr~llqng endO
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, ~ catamenial tampon ~imllar to that de~cribe~ ~n : ~xample XVI but whereln the l~ading two thiPds sur~ace o~
~oth the ab~30r~ent core and ~luid per~iou~ cover h~v~
~ppIl~d thereto 1.0 mg. ~er square inch o~ tri~od~u~
~thylenedi~nine tetra~cet~te~
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PPC 1~5 EXAMPLE XVIII
A cream stick was prepared by admixin~ at about 60C the ~ollowing materials in the indicated proportion~:
Wei ght ln ~ ~:rams Ozokerite wax ~ 48.o Car~auba wax 32.0 Candellila wax 64 ~ 0 Emcol 249~3K1 42 . o Tenox 42 0 . 8 Benton M-203 8090 Talc 120. 0 Propyl paraben o.8 Neutral blen~ of Na2EDTA 40. 0 plus Na4EDTA
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1 Alkoxylated alcohol (Witco Chemical Company) ~ Trademark 20~ Butylated hydroxy anisole~ 20~ butyla,ted hydroxy toluene, 60% corn oil (Eastman Chemical Products Inc.) Trademark ~ . .
', J Modi~ied bentoni~e (National Lead Compan;,~) _ Tradema.rk Prepared as described in the Footnote 5 ~o Table III.
~, Therea~ter the mixture was poured inko chilled molds to provide a final product in chilled stick form.
~0 Test panelists were provided with two coded cream stlcks ~or axillary deodorant use, one stick being of the above composition and the other stick of similar composition but not containing the blend of the two sodium ethylene-. . .
3~3 .
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.. - . ... ., . : .' '- . :. ' ' dlamlnetetraacetate saltsO The test panelists were not informed as to which stick contained ~he EDTA salts~
The sub~ects applied one stick to one axllla and the other ~tick to the othe;r axilla and a~t~r e~ch appllcat~on the ~ub~cts made qualltative evaluations on odor lntensity. The re~uit.s are given i~ Table VI.
; TABLE VI
Odor Intensity by Sel~-Evaluatlon Panelist Control Axilla Te~t Axilla A Strong No odor B Very Str~ng No Odor . C ~ery Strong No Odor D Strong No Odor E Strong No Odor ~5 F ~ Very Strong Slight G Yery Strong Sligh~ ~~
H Stro~g Sllght I V~ry Strong Sllgh~
J Very Strong Sl~ght ~O K Strong Slight L Strong Slight ; M V~ry Strong Sli~ht .
~ EXoMPLE XIX
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An ~erosol co~posltion is prepar~d by ~irst admixing the ~ollo.wing materials in the indicated pr~portions:-' .
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Micropulverized Talc 2,50 Micropulverlzed Na3EDTA a 0 50 Fragra2lce 0. 16 Anhydrous ethanol 0, 20 Isopropyl myristate o.60 Therea~ter, the mlxture ls placed ln vesselssuitable for pressurization (cans) and the followln~
propellants added ln the indicated proportions:
reon 11 47002 ~reon 122 47.20 Trichloromono~luoromethane (E.I. duPont de Nemours & Co.) 2Dlchlorodifluoromethane (E~Io duPont de Nemours & Co.~
- ~ra emark ` . - '.
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PPC 1~5 EXAMPLE XX
~_ . .
In an experlment carrled out in a manner ~lm~lar to tha~
de6crlbed in Example ~, t¢st samples were prepar~d by ~ddlng ~o samples o~ sterlle plasma in6~culated with ~,orynebacteritlm one of the following aminopolycarboxyllc acid compounds:
dl~odlum ethylenediamlnetetraacetake (Na2EDTA)~ N~hydroxy~
ethylethylenediamlnetriacetlc acld (HEDT~), dle~hyl~netr~amine-pentaacetlc acid (DTPA~, eth~lene.glycol bl~(~minoethyl ether)~
ketracetic acid (EGT~), and a triethanolamine salk o~
ethylenedl~minetetraceti~ acId (TEDTA~ prepared by addlng triethanolamine to aqueous ethylenedlaminetetraac~tic acld to a pH of 6.3. The amount o~ ~minopolycarboxyllc acid compound added to the samples w~s that su~ficl~nt to p~ovlde ln the te~t medla 0.2% by weight Or the am~nopolycarboxyllc acid co~pound (calculated as the ~ree acld3. In ~ddition two cont~ol samples wer~ prepared~ One c~ntrol ~ample W~8 0 unmodified ~terlle pla~ma ~unlnoculated and containln~ no amlnopolycarboxylic acid compound~ and the ~econ~ control ~ample was an inoculated ~ample conta~nlng no am-7n3~olycarboxyllc A acid compound and ~erved a~ untr~ated control. The ~mple~
~0 were incubated ~nd t~ted ~or ~ree ~atty acids a~ pr~iously ~ ~e~cribed. Th~ re~ults obtalned were as ~ol.o~sO
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1~5~S~
PP~ 18 TA~ VII
~.
~ I~o~aleric Unkreated Sterile Plasma 0 0 Corynebacterium Inocul~
No AminopolycarboxYIic Acid C~mpound 105 187 Coryneb~c terlum Inoculum 0 0 0.1% Na~EDTA
Corynebacke~ium Inoculum O . O
O.1% HEDTA
Corynebacterlum Inoculum O
0.1% DTPA
Corynebacterlum Inoculum O O
~ 0~1~ EGTA
.Corynebacterium Inoculum O
~ 0~1% TE~TA
.
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~; Sanitary napklr~s ar~ prep~red ha~rlng an aminopolycarboxy-llc acid compound lmpregr~ated on th~ up~er sur~a~ce o~ ~he ~bsorbent core ~nd fluid perv~ious cover ln a m~nner ~imil~ GO that . .
d~cribed in Example. XIV and XV except that they ~rs modlried w~th respect to the amlnopolycarboxyllc ~cid c~mpound ~nd O amount employed per square lnch o~ surrace area a~ ~oll~ws: -Di~odium e1;hylene glycol'bi~ninoethy~ ~l;her) ~ :
tetracetate3 3 mg. p~r squar~ inchO
, ~ . . .
Sodium lminodi~cetate9 2 mg. per ~u~re inGh.
~ 3thylenediQmlnetetra(methylenephospho~lc ~cid~
; ~ neutralized with dlethanolamine to p~ 6030 1~5 mg~ per . , .
- sguare inch.
]?enta~odl~n nltrilotrls ~methylerl~phosphor!at2 ) 3 ' 2 mg., per square 'i~nch.
~3thylenedi~nirlete1;ra (methylenes~t~on:Lc ac ld ) neutra-zed wlth tri~thanolamine to pH 6.3D 2 mg, p¢r square inchO
.y~ _ ~75 . ~ I
A cream stick is prepared ln the mann~r described in Example X~III by ~dmixing the ~ollowing materials in the indicated proportions:
Welght lnrams Ozokerite wax 48.o Carnauba wax 3200 : Candellila wax 64.o Emcol 249-3K * 42.0 Tenox 4 * o.~
Benton M~20 * 80~0 Talc ~20.0 ; Propyl paraben * 0.8 Triethanolamlne salt of ethylanediaminetetraacetic acid 50DO .' , ~.
The stick. may be applled to the dermal sur~aces of the axilla to inhibit ~ormatlon o~ odorous ~atty acids by actlon of --; ~ on lipoidal materlalsO
: Compositions suitable ~or topical applic~tion to inhibit ~atty acid productlon ~rom llpoidal materials by 5~æ;~__ cterium may be prepared by intimately admixlng the components specir~ed ~0 below in the amounts ind1cated to obt~n treating compositions:
* Trademark ~ . ' ' .
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5~S~
PP~ 185 Composition A
N~Hydroxyethylethylene~
diaminetetraacetlc acid 10 parts by weight Triethanolamlne 10 part~ by weight Wltch haxel 80 parg~ by weight Compositlon ~ ..
Ethylene glycol bls(amino~thyl- .
ether)tetraacetic acid 13 par~s by w~ight-Triethanolamine13.8 part~ b~ weight ~ltch hazel73.2 part8 by weleht Composi~1on C
, ~:thylenedi~mlnetetr~acetic acid 10 ~rtæ by wei~3ht Triisopropanolamine17~7 ~arts by weighJc ~iteh hazel7203 parts by weighti , , ~PIE xxrv , A composition suitable ~or ap~llcatlon to dermal ti3~ue ~s ~repared by Int~mately admixlng the.follow~ng:
~ ' ' '' thylenedlaminetetracetlc acid10 part~ by welght Trlethanolamlne 13.8 p~rts by ~elght :~
Wltch hazel 76.? p~rts by w~lght . . :
Thi~ composition may be applled to de~mal tlssue~ ~o lnhIblt t~v~l~pment o~ in~l~mmatory ~kin c~nditlon~ resul~ing from . ., , , ' 5~
PP~ 185 fatty acid~ arising ~rom secreted llpoidal materi~ls b~
the action of C -~Ae _ t;hereon. In auch use daily application is made by swabbing the af~ected area o~ the dermal ~urface and repeating such appllcatlnn untIl the i conditlon is allevlated. Further ap~lic~tion may be made on the appearance Or development of the undesirable conditions to prevent ~urther develo~ment o~ said co~dltlons.
EXAMPLE X_V_ The composition o~ Example XXIV was employed to determine efflcacy in lnhibiting unde~lra~le infla~matory conditions of the skin typical of acne~ ~he undeslr~ble condltions may be tho6e descr~béd as the exi~tence o~
erythema and the presence o~ papules and pu~tules.
' In the determine,tiong 81x sub~ects wi th ælmilar degreP
of ~nflammator~r conditions on both sides of` the :E~ce æ,pplied the abo~e composition to one side of th~ ~ace a~ter ~lrst maklng determlnations on the number o~ ~rythem~u~ papules ~nd pustules on each ~ide o~ the face~ herein termed '~lesi~ns, "
The other side o~ the f~ce served as control. T~e applicatlon~
~ i .~. 20 were made twice daily to one slde o~ the face ~ter ~irst ~eparateIy clleaning each side of the faee9 and the application ; wa~ contlnued ror a period of three w~eksO At the e~d of thls per~od the percent change ln the number o~ les~ons on t~ treated and untreated sides of the race were determlned7 The results wl~re as follows: :
`: :
TAB
Percent Chang~
Panellet Treeted ~
70% Reduction 6% Reduction 2 7Q% " 55% Increa~e 3 5~'~6 " 7
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.. - . ... ., . : .' '- . :. ' ' dlamlnetetraacetate saltsO The test panelists were not informed as to which stick contained ~he EDTA salts~
The sub~ects applied one stick to one axllla and the other ~tick to the othe;r axilla and a~t~r e~ch appllcat~on the ~ub~cts made qualltative evaluations on odor lntensity. The re~uit.s are given i~ Table VI.
; TABLE VI
Odor Intensity by Sel~-Evaluatlon Panelist Control Axilla Te~t Axilla A Strong No odor B Very Str~ng No Odor . C ~ery Strong No Odor D Strong No Odor E Strong No Odor ~5 F ~ Very Strong Slight G Yery Strong Sligh~ ~~
H Stro~g Sllght I V~ry Strong Sllgh~
J Very Strong Sl~ght ~O K Strong Slight L Strong Slight ; M V~ry Strong Sli~ht .
~ EXoMPLE XIX
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An ~erosol co~posltion is prepar~d by ~irst admixing the ~ollo.wing materials in the indicated pr~portions:-' .
' .: . . ..
.
Micropulverized Talc 2,50 Micropulverlzed Na3EDTA a 0 50 Fragra2lce 0. 16 Anhydrous ethanol 0, 20 Isopropyl myristate o.60 Therea~ter, the mlxture ls placed ln vesselssuitable for pressurization (cans) and the followln~
propellants added ln the indicated proportions:
reon 11 47002 ~reon 122 47.20 Trichloromono~luoromethane (E.I. duPont de Nemours & Co.) 2Dlchlorodifluoromethane (E~Io duPont de Nemours & Co.~
- ~ra emark ` . - '.
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PPC 1~5 EXAMPLE XX
~_ . .
In an experlment carrled out in a manner ~lm~lar to tha~
de6crlbed in Example ~, t¢st samples were prepar~d by ~ddlng ~o samples o~ sterlle plasma in6~culated with ~,orynebacteritlm one of the following aminopolycarboxyllc acid compounds:
dl~odlum ethylenediamlnetetraacetake (Na2EDTA)~ N~hydroxy~
ethylethylenediamlnetriacetlc acld (HEDT~), dle~hyl~netr~amine-pentaacetlc acid (DTPA~, eth~lene.glycol bl~(~minoethyl ether)~
ketracetic acid (EGT~), and a triethanolamine salk o~
ethylenedl~minetetraceti~ acId (TEDTA~ prepared by addlng triethanolamine to aqueous ethylenedlaminetetraac~tic acld to a pH of 6.3. The amount o~ ~minopolycarboxyllc acid compound added to the samples w~s that su~ficl~nt to p~ovlde ln the te~t medla 0.2% by weight Or the am~nopolycarboxyllc acid co~pound (calculated as the ~ree acld3. In ~ddition two cont~ol samples wer~ prepared~ One c~ntrol ~ample W~8 0 unmodified ~terlle pla~ma ~unlnoculated and containln~ no amlnopolycarboxylic acid compound~ and the ~econ~ control ~ample was an inoculated ~ample conta~nlng no am-7n3~olycarboxyllc A acid compound and ~erved a~ untr~ated control. The ~mple~
~0 were incubated ~nd t~ted ~or ~ree ~atty acids a~ pr~iously ~ ~e~cribed. Th~ re~ults obtalned were as ~ol.o~sO
: .:
' ' . 4 ;' ' ' ... . :
1~5~S~
PP~ 18 TA~ VII
~.
~ I~o~aleric Unkreated Sterile Plasma 0 0 Corynebacterium Inocul~
No AminopolycarboxYIic Acid C~mpound 105 187 Coryneb~c terlum Inoculum 0 0 0.1% Na~EDTA
Corynebacke~ium Inoculum O . O
O.1% HEDTA
Corynebacterlum Inoculum O
0.1% DTPA
Corynebacterlum Inoculum O O
~ 0~1~ EGTA
.Corynebacterium Inoculum O
~ 0~1% TE~TA
.
~' ' ~ ' .
~; Sanitary napklr~s ar~ prep~red ha~rlng an aminopolycarboxy-llc acid compound lmpregr~ated on th~ up~er sur~a~ce o~ ~he ~bsorbent core ~nd fluid perv~ious cover ln a m~nner ~imil~ GO that . .
d~cribed in Example. XIV and XV except that they ~rs modlried w~th respect to the amlnopolycarboxyllc ~cid c~mpound ~nd O amount employed per square lnch o~ surrace area a~ ~oll~ws: -Di~odium e1;hylene glycol'bi~ninoethy~ ~l;her) ~ :
tetracetate3 3 mg. p~r squar~ inchO
, ~ . . .
Sodium lminodi~cetate9 2 mg. per ~u~re inGh.
~ 3thylenediQmlnetetra(methylenephospho~lc ~cid~
; ~ neutralized with dlethanolamine to p~ 6030 1~5 mg~ per . , .
- sguare inch.
]?enta~odl~n nltrilotrls ~methylerl~phosphor!at2 ) 3 ' 2 mg., per square 'i~nch.
~3thylenedi~nirlete1;ra (methylenes~t~on:Lc ac ld ) neutra-zed wlth tri~thanolamine to pH 6.3D 2 mg, p¢r square inchO
.y~ _ ~75 . ~ I
A cream stick is prepared ln the mann~r described in Example X~III by ~dmixing the ~ollowing materials in the indicated proportions:
Welght lnrams Ozokerite wax 48.o Carnauba wax 3200 : Candellila wax 64.o Emcol 249-3K * 42.0 Tenox 4 * o.~
Benton M~20 * 80~0 Talc ~20.0 ; Propyl paraben * 0.8 Triethanolamlne salt of ethylanediaminetetraacetic acid 50DO .' , ~.
The stick. may be applled to the dermal sur~aces of the axilla to inhibit ~ormatlon o~ odorous ~atty acids by actlon of --; ~ on lipoidal materlalsO
: Compositions suitable ~or topical applic~tion to inhibit ~atty acid productlon ~rom llpoidal materials by 5~æ;~__ cterium may be prepared by intimately admixlng the components specir~ed ~0 below in the amounts ind1cated to obt~n treating compositions:
* Trademark ~ . ' ' .
, .. ..... . ...
5~S~
PP~ 185 Composition A
N~Hydroxyethylethylene~
diaminetetraacetlc acid 10 parts by weight Triethanolamlne 10 part~ by weight Wltch haxel 80 parg~ by weight Compositlon ~ ..
Ethylene glycol bls(amino~thyl- .
ether)tetraacetic acid 13 par~s by w~ight-Triethanolamine13.8 part~ b~ weight ~ltch hazel73.2 part8 by weleht Composi~1on C
, ~:thylenedi~mlnetetr~acetic acid 10 ~rtæ by wei~3ht Triisopropanolamine17~7 ~arts by weighJc ~iteh hazel7203 parts by weighti , , ~PIE xxrv , A composition suitable ~or ap~llcatlon to dermal ti3~ue ~s ~repared by Int~mately admixlng the.follow~ng:
~ ' ' '' thylenedlaminetetracetlc acid10 part~ by welght Trlethanolamlne 13.8 p~rts by ~elght :~
Wltch hazel 76.? p~rts by w~lght . . :
Thi~ composition may be applled to de~mal tlssue~ ~o lnhIblt t~v~l~pment o~ in~l~mmatory ~kin c~nditlon~ resul~ing from . ., , , ' 5~
PP~ 185 fatty acid~ arising ~rom secreted llpoidal materi~ls b~
the action of C -~Ae _ t;hereon. In auch use daily application is made by swabbing the af~ected area o~ the dermal ~urface and repeating such appllcatlnn untIl the i conditlon is allevlated. Further ap~lic~tion may be made on the appearance Or development of the undesirable conditions to prevent ~urther develo~ment o~ said co~dltlons.
EXAMPLE X_V_ The composition o~ Example XXIV was employed to determine efflcacy in lnhibiting unde~lra~le infla~matory conditions of the skin typical of acne~ ~he undeslr~ble condltions may be tho6e descr~béd as the exi~tence o~
erythema and the presence o~ papules and pu~tules.
' In the determine,tiong 81x sub~ects wi th ælmilar degreP
of ~nflammator~r conditions on both sides of` the :E~ce æ,pplied the abo~e composition to one side of th~ ~ace a~ter ~lrst maklng determlnations on the number o~ ~rythem~u~ papules ~nd pustules on each ~ide o~ the face~ herein termed '~lesi~ns, "
The other side o~ the f~ce served as control. T~e applicatlon~
~ i .~. 20 were made twice daily to one slde o~ the face ~ter ~irst ~eparateIy clleaning each side of the faee9 and the application ; wa~ contlnued ror a period of three w~eksO At the e~d of thls per~od the percent change ln the number o~ les~ons on t~ treated and untreated sides of the race were determlned7 The results wl~re as follows: :
`: :
TAB
Percent Chang~
Panellet Treeted ~
70% Reduction 6% Reduction 2 7Q% " 55% Increa~e 3 5~'~6 " 7
4 6~% " 2~
- 62% i~ 3% Reduction 6 595~ " ~%
Although in the past, unde~irable produçts re~ul~ g ~rom microbial actlon on body ~creti~n~ ha~e been inl:libited 10 by klll o~ mlcroor~anl~ms, It ha~ now ~een disco~ePed that by u~e of ~he composition~ of the pre~ent :Ln~entior~ the desired :-~nhibitory action may be acc~nplished without th~ necessity o~ kill o~ the organi~ms. ThU~ or ex~mple,~ ~rhen gr~l~Jth o~
Proteue mirabills in he~arinlzed blood at 37 wi~h arld ~5 without added ~isodlum ethylenediaminetetraac~tate was followed over a 24-hour periodJ there W~8 ~o~nd ~o be no detrimerltal eîfect on the growth o~ or~anism~ as c~n b~
~een in the ~ollowirlg table:
__ Bacterial Count Blood Ixloculated '------~L~ O Hours : . 24 Hours No Na2EDTA 100 x 104 182 x 107 2% Na2E~TP~ 100 x 104 : 23:L x 1t:)7 . , .
.
:
!
. , `
~ 6 .
- 62% i~ 3% Reduction 6 595~ " ~%
Although in the past, unde~irable produçts re~ul~ g ~rom microbial actlon on body ~creti~n~ ha~e been inl:libited 10 by klll o~ mlcroor~anl~ms, It ha~ now ~een disco~ePed that by u~e of ~he composition~ of the pre~ent :Ln~entior~ the desired :-~nhibitory action may be acc~nplished without th~ necessity o~ kill o~ the organi~ms. ThU~ or ex~mple,~ ~rhen gr~l~Jth o~
Proteue mirabills in he~arinlzed blood at 37 wi~h arld ~5 without added ~isodlum ethylenediaminetetraac~tate was followed over a 24-hour periodJ there W~8 ~o~nd ~o be no detrimerltal eîfect on the growth o~ or~anism~ as c~n b~
~een in the ~ollowirlg table:
__ Bacterial Count Blood Ixloculated '------~L~ O Hours : . 24 Hours No Na2EDTA 100 x 104 182 x 107 2% Na2E~TP~ 100 x 104 : 23:L x 1t:)7 . , .
.
:
!
. , `
~ 6 .
Claims (4)
1. An absorbent catamenial dressing comprising an absor-bent core and a liquid pervious cover around said core, said dressing containing within the structure on at least the por-tions of the surface area thereof first to intercept menstrual fluids in use, an amino acid compound in an amount of at least about 0.001 gram per square inch.
2. An absorbent catamenial dressing according to Claim 1 wherein the amino acid compound is an aminopolycarboxylic acid compound.
3. An absorbent catamenial dressing according to Claim 2 wherein the aminopolycarboxylic acid compound is an ethylene-diaminetetraacetic acid compound.
4. An absorbent catamenial dressing as defined in Claim 1 wherein the amino acid compound is present in an amount ranging from about 0.004 gram per square inch to about 0.1 gram per square inch.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA317,237A CA1075151A (en) | 1974-06-12 | 1978-12-01 | Inhibiting production of undesirable products on body surfaces and environs |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US478662A US3920020A (en) | 1974-06-12 | 1974-06-12 | Inhibiting production of undesirable products on body surfaces and environs |
US57448875A | 1975-05-05 | 1975-05-05 | |
CA230,087A CA1066624A (en) | 1974-06-12 | 1975-06-12 | Inhibiting production of undesirable products on body surfaces and environs |
CA317,237A CA1075151A (en) | 1974-06-12 | 1978-12-01 | Inhibiting production of undesirable products on body surfaces and environs |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1075151A true CA1075151A (en) | 1980-04-08 |
Family
ID=27425849
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA317,237A Expired CA1075151A (en) | 1974-06-12 | 1978-12-01 | Inhibiting production of undesirable products on body surfaces and environs |
Country Status (1)
Country | Link |
---|---|
CA (1) | CA1075151A (en) |
-
1978
- 1978-12-01 CA CA317,237A patent/CA1075151A/en not_active Expired
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