CA1195619A - Non-irritating dentifrice - Google Patents
Non-irritating dentifriceInfo
- Publication number
- CA1195619A CA1195619A CA000423485A CA423485A CA1195619A CA 1195619 A CA1195619 A CA 1195619A CA 000423485 A CA000423485 A CA 000423485A CA 423485 A CA423485 A CA 423485A CA 1195619 A CA1195619 A CA 1195619A
- Authority
- CA
- Canada
- Prior art keywords
- protein
- dentifrice
- dentifrice according
- weight
- fraction
- 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
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
- A61K8/463—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfuric acid derivatives, e.g. sodium lauryl sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/75—Anti-irritant
Abstract
Abstract of the Disclosure A dentifrice composition containing an anionic surfactant, and a minor amount of a water soluble positively charged protein hydrolysate having an isoionic point above 7, and a Bloom gel value of zero, selected from the group consisting of a protein hydrolysate fraction containing high concentrations of basic amino acids or a quaternary derivative of a protein hydrolysate, which counters the irritation to the oral tissue and reduces the bitterness caused by said anionic surfactant, without reducing its foaming and cleansing properties.
Description
The present invention reLates to novel oral compositions wh;ch are substantlally non-irritating to the oral tissue, comprising Ull anionic surEactant and a positively charged water soluble protein hy~lrolysate fraction containing a high concentration oE basic amino ~.lCi~s or a qttaterna.ry derivative o a protein hydrolysate. The protein hyclrolysate raction is obtained by extractlon Erom a partially hydrolyzed protein mixture by means oE ion exchange separation with an anion exchange resin. The quaternary derivative is obtained by quaternizing a protein hydrolysate mixture by chemically modifying the available terminal amino groups of the protein.
11'356~9 9~ _n~ ~n~ ~rior Ar~
. . I' Sodium lauryl sulfate (S~S) in den-tifrices is known to cause adverse reactions to oral tissue as shown in R. C.
Caldwell and R. E. Stallard~
196, W. B. Saunders (1977); L. J. Guarnieri, No. 661 (1974); and L. J. Guarnieri, ~hesis, University of Indiana (1970). One example is gingival irritation. It is al50 believed that SLS is responsible for sloughirl~ of the oral mucosa. ~n addition, SLS is responsible for an adverse effect on taste buds causing certain foods to have a bitter tas-te.
Furthermore, the SLS itself, in the dentifrice tas-tes bitter.
U~ S. Patent No. 2,812,284 shows that the soaps and ~yrlthe-tic detergents in dentifrices cause a h~r~h an~/or ~itlcr tu3te, which patente0 has overcome by u~ing a mixture of two specific groups of anionic surf`act~lts7 i-eO~ the sulfonate ~alts o~ monoglycerides of C10-Cl8 fatty acids and the sulfate salts o~ ClO~C18 fatty alcohols, in a 3:1 ratio respectively.
However, the problem of oral irritation due to the presence of anionic surfactants in the dentifrice is not mentioned in
11'356~9 9~ _n~ ~n~ ~rior Ar~
. . I' Sodium lauryl sulfate (S~S) in den-tifrices is known to cause adverse reactions to oral tissue as shown in R. C.
Caldwell and R. E. Stallard~
196, W. B. Saunders (1977); L. J. Guarnieri, No. 661 (1974); and L. J. Guarnieri, ~hesis, University of Indiana (1970). One example is gingival irritation. It is al50 believed that SLS is responsible for sloughirl~ of the oral mucosa. ~n addition, SLS is responsible for an adverse effect on taste buds causing certain foods to have a bitter tas-te.
Furthermore, the SLS itself, in the dentifrice tas-tes bitter.
U~ S. Patent No. 2,812,284 shows that the soaps and ~yrlthe-tic detergents in dentifrices cause a h~r~h an~/or ~itlcr tu3te, which patente0 has overcome by u~ing a mixture of two specific groups of anionic surf`act~lts7 i-eO~ the sulfonate ~alts o~ monoglycerides of C10-Cl8 fatty acids and the sulfate salts o~ ClO~C18 fatty alcohols, in a 3:1 ratio respectively.
However, the problem of oral irritation due to the presence of anionic surfactants in the dentifrice is not mentioned in
-2~
r---~I ~L9S~
aforesaicl ~atentO
Likewise~ the use of proteins in oral preparations for . sundry purposes is shown in U. S~ Patent NoO 19470p794 wherein casein, gelatin and the like is pre~ent in the dentifrice as a means o~ retarding the rate of the production of carbonic acid. U. S. Patent No. 2,154,168 disclos~s an edible denti.~rice ¦
containing casein or o~her animal or vegetable protein adhesive carrier as a mean~ of buffering the pH o~ the compssi-tion to prevent accumulations of tooth-destroying acids~ U. S. Patent No. 4,154,813 utilizes peptides as the pH adjusting means in order to combat caries which occurs at low pH. U~ S. Patent No~ 4,165,368 uses gelatin as a viscosity modifier to improve the flowability of the toothpaste, Ho~Jever~ none of aforesaid pat.ent compositions contain an anionic surfaetant, nor reco~-nize th~ problems of or~l tissue irri-tation and the bitter taste associated with the presence of said anionic sur.f~Lc tarlt.
Oral compositions co~taining both an;.onic surfactants and protein~ are also well known in the art as disclosecl in U. S. Patent No. 359~5,957~ wherein gelatin is used as a cor~
rosion inhibitor~ In U. S, Patent No, 396~8,974, a water insoluble partial salt of collagen is used in the formation
r---~I ~L9S~
aforesaicl ~atentO
Likewise~ the use of proteins in oral preparations for . sundry purposes is shown in U. S~ Patent NoO 19470p794 wherein casein, gelatin and the like is pre~ent in the dentifrice as a means o~ retarding the rate of the production of carbonic acid. U. S. Patent No. 2,154,168 disclos~s an edible denti.~rice ¦
containing casein or o~her animal or vegetable protein adhesive carrier as a mean~ of buffering the pH o~ the compssi-tion to prevent accumulations of tooth-destroying acids~ U. S. Patent No. 4,154,813 utilizes peptides as the pH adjusting means in order to combat caries which occurs at low pH. U~ S. Patent No~ 4,165,368 uses gelatin as a viscosity modifier to improve the flowability of the toothpaste, Ho~Jever~ none of aforesaid pat.ent compositions contain an anionic surfaetant, nor reco~-nize th~ problems of or~l tissue irri-tation and the bitter taste associated with the presence of said anionic sur.f~Lc tarlt.
Oral compositions co~taining both an;.onic surfactants and protein~ are also well known in the art as disclosecl in U. S. Patent No. 359~5,957~ wherein gelatin is used as a cor~
rosion inhibitor~ In U. S, Patent No, 396~8,974, a water insoluble partial salt of collagen is used in the formation
-3 . I
~95~
of a stable gel for use in cosmetics containing anionic surfac-tants. U. S. Patents No. 4,0589595 and 4?05~596 disclose stable enzymatic toothpastes containing a neutral protease and a partially hydrolyzed protein~ plus anionic or nonionic sur-factant.
The purposesof the proteins ln the above clted patents are to impart vlscoslty, provide enzymatic activity, inhibit corrosion, malntain a high pH in the dentifrice, or retard the rate of development of carbonic acid. None of sald proteins are reported to counter the irritation to oral mucosa caused by anionic surfactants such as sodium lauryl sulfate.
However, none of the above cited art discloses a substantially non-irritating dentifrice composition comprising an antonic surfactant and a minor amount of a water soluble llydro;Ly7.ed protein fraction rich in posltively charged amino acids or n quatern:L7.ed hydroly7ed proteln~ hav:Lng an isotonLc poin~ ~rea~er than 7 and a Bloom gel value of zero.
Summary_of the Invention It has been unexpectedly found that the additlon oE a partia y hydrolyzed plO e ein frac t i OD rich iD p O A i t i ely charged
~95~
of a stable gel for use in cosmetics containing anionic surfac-tants. U. S. Patents No. 4,0589595 and 4?05~596 disclose stable enzymatic toothpastes containing a neutral protease and a partially hydrolyzed protein~ plus anionic or nonionic sur-factant.
The purposesof the proteins ln the above clted patents are to impart vlscoslty, provide enzymatic activity, inhibit corrosion, malntain a high pH in the dentifrice, or retard the rate of development of carbonic acid. None of sald proteins are reported to counter the irritation to oral mucosa caused by anionic surfactants such as sodium lauryl sulfate.
However, none of the above cited art discloses a substantially non-irritating dentifrice composition comprising an antonic surfactant and a minor amount of a water soluble llydro;Ly7.ed protein fraction rich in posltively charged amino acids or n quatern:L7.ed hydroly7ed proteln~ hav:Lng an isotonLc poin~ ~rea~er than 7 and a Bloom gel value of zero.
Summary_of the Invention It has been unexpectedly found that the additlon oE a partia y hydrolyzed plO e ein frac t i OD rich iD p O A i t i ely charged
-4-~95~
amino acids or a qua~ernized hydrolyzed protein, having an isoionic point above 7 and a Bloom gel value of zero, to an anionic surface active agent-containing dentifrice counters the adverse reactions of said anionics which include reduced gingival inflammation, reduced sloughing of the oral mucosa, reduced bitterness of foods, reduced bitterness of the dentifrice itselfJ but surpri.singly not a con-comitant :Loss .in foaming power or detergency.
Accordingly, a primary object of present invention is to reduce the adverse ef:Eect that anionic surfactants in a dentifrice 1~ have on human oral tissue.
The present invention attempts to provide a substantially non-irritating dentifrice of improved flavor contai.ning an anionic surfactant and a positively charged partially hydrolyzed protein fraction rich in amino acids or a quaternized protein hydrolysate m:i~ture.
Pre:ferably, the dentifrice of the present invention has foaming and detergency properties of the aniollic surfactant which are not decreased by the presence of the water soluble posi.tively cl~ rgecl p~rt:i.ally hyd.rolyzed protein :fraction or the quaterni.zecl l~ydrolyzed protein.
6~
Additional, advantages and novel features of the inven-tion will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention.
In accordance with the present invention there is pro-vided a substantially non-irritating dentifrice composition compris-ing an anionic surfactant, and a water soluble positively charged partially hydrolyzed protein having an isoionic point above 7, and a Bloom gel value of zero, selected from the group consisting of a protein hydrolysate fraction containing a high concentrati.on of basic amino acids, and a quaternary derivative of the partially hydrolyzed protein, in a dental vehicle.
More specifically, present invention relates to a dentifrice composition, which may be in the form of a powder, paste or l:iquid, comprising an anionic sur:Eace active agent and about 0.2 - 5% of a positively charged partially hydrolyzed protein _~ ~ ~ ~S6~l~
~rac~ion contalning high conc~ntra~ion~ of ba~ic ami~o acids obtained by extraction from a partially hydroly~d protein mix-ture ~nd isolatiora by ion exchange ~r~atmen~ wi~h an a~ion exchange resin9 or a positive~r charged quaternized hydrolyæed protein, in a dental vehicl~0 The positively charged protein hydrolysat~ fraction utili~ed in present inven~ion con~ins a high eoncentration o~ ba~ic amino acids~ ha~ an isoioniG poin~ greater tha~ 7 ~nd a Bloom g~l value of æero; aI~d a molecular weight of about 600 to 12,000, and is a solid powdered water ~olubls mat~rial9 The positively charged quaternlze~ hydrolyzed pro~ein used in pres~nt lnve~tion i~ a catio~ic qua~ernary derivative of hyàrolyz~d collagen protein,, a product of Crnda IncO of New York, kno~n as Cro~ein Q~, having a m~ni~ pI of 905-1005, and is an off-white free flowing powder5, The free amlno groups in the protein molecul~ r~ac~ with the quater~a~ ammonium r~aat~n~ to ~orm the qua~arnized d~rivatlve,D
The positively chargad prot~in constltutes about 002 to 5~ and preferab~r 0~,7 ~o 1..3j~ by weight o.~ ~he dentifrice containing about 0~5 5% and pre.~erably 1~3~ by we~;h~ o:f an anioni~ surfactan~ Said positively charged pro~sins r~d~lc~
the oral irritation ~nd th- bitter fla~sr og~ the anionic sur~
119561'~
factant witihout decr~asi~g ~he :Eoaa~ng and d~ergenc~ properti~s I
of the compo~i~ioll5 The po~ikively eharged, partially hydroly~ed protein ~ractior~ having a high concen~ration of basic amino acids is prepar~d by ex~rac~ion from a ~lydroly~ed protei~ mix~ure and ~solakion o~ the pos~tivel~ charged fraction by mean~ of ion e~cchangz trea~men~ with a~ anio~ ¢xchange resi~., More specific~
ally~ said protei~ mixture i~ treated with an aniorl sxchang~
resi~i9 f`ollowed by dialy~is. The hydrol~sate fraction may be used as such or may op~ionally be fre~e dried ~o remove the water therefrom. The pro~ein mixtur~ may ~e an animal collageIa h~rdrolysat~, re~ultilig from ~ha hydrolysi~ o~ ~ protein with an acid or base or e~zyme. Wh~n th~ protei~ is hydrolyz~d by an acid or base9 i~ is n~cessary to remove ~ho salts (NaCl) ~ormed during sa.id hy~roly~is~ prior to treakment of said prow ~e~n h~droly~ata mix~ure with ~he ~Ilion exchallg~a resixi~ The ~alt~ can be removed b~r dialy~1~ of ~he pro~;ein hydro:lysate m:Lx-~ure., The ~our~e of the an:lmal collag~n hydro.~ysate may be lea~her ~crap~ pi~s :~ee~ a~ hoove~9 bollas3 skin or fee~ of E~ork or be~f~ Coms~lea~cial prod~ck~ suc~ as Sgelpan PP 37~ from StE3pa~ Chemical Co." Ghicago~ ïlli~oi~, a~ a~imal cellag~ ¦
h~drol~sa~e hydrolyæed at high pH (~a~OH32) ~ro~ l~ath~r ~craps,o, ' ~I/D~D
1, _ _ S631 ~
and Lexein lO0 P from Inolex Corporation, Chicago, Illinois, an animal collagen hydrolysate from pigs feet and hooves, hydro-lyzed by means of steam and/or acid followed by enzyme treatment, are typical collagen protein mixtures from which the positively charged protein hydrolysate fractions may be extracted and iso-lated.
More specifically, the process of preparing the posi-tively charged protein hydrolysate fraction containing a high concentration of basic amino acids comprises the steps of treat-~0 ing a partially hydrolyzed protein mixture with an anionexchange resin to absor~ negatively charged groups from the pro-tein onto the resin and to substitute acetate groups or other negative]y charged groups therefor on the resin and dialyzing the resultant anion-exchanged protein hydrolysate fraction to remove said resin-substituted negatively charged groups. A pre-ferred additional first step comprises dialysis of the hydrolyzed protein mixture prior to treatment with the anion exchange resin .in order to remove salts and other impuri-ties which may be present as a result of protein hydrolysis. ~n optionally adcli-t.ional fi.na]. step comprises Ereeze drying the positively chargedprotein h~drolysate ~raction to remove the water therefrom and res~rve it for Euture use. Ion exchange chromatography is a well lcncwn procedure described in the prior art. The batch phase ion exchange chromatography procedure for separation of proteins, based on charge, is described in an article by S.M. Vratsanos and I.D. ~andel entitled "Isolation of Cationic Salivary Proteins"
in the Journal of Dental ~esearch, Volume 56, B109, special i~sue B, 1977.
* trade mark g ~$~j~
The column ion exchange chromatography method is described in a 1973 brochure by Pharmacia entitled "Sephadex Ion Exchangers ~ A Guide to Ion Exchange Chromatography". The optimal ratio of ion exchange resin -to protein for fractionation of a hydrolyzed pro-tein mixture by ion exchange Ghromatography is approximately 20:1. This represents the ratio of resin to protein required to just absorb the anionic proteins onto the resin, but not absorb the neutral or cationic proteins.
Any suitable anion exchange resin may be utilized in the process of producing the positively charged protein hydroly-sate fractions containing a high concentration of basic amino acids. The polystyrene- and polysaccharide-based anion exchang~
ers are most often used. The most important class of anion-exchange resins is based on the introduction of basic groups such as ~uaternary amino groups into a styrene-divinylbenzene copolymer a~ter polymerization. These are strongly basic anion exchange resins. E~amples of strong base anion exchangers are Dowex 1 and 2 resins by Dow Chemical Companyr Amberlite IR~
~01 and 410 resins of Rohm and Haas Company, De-Acidite FF and Duolit~s ~-40 and ~ ~2 oE Diamond Shamrock Company and Bio-Rad 1 resin of Bio-* trade mark ~, .., i ~ ! ' ' 9 5 ~
Rad Company~ Wea~ bas~ anion exchangers haY~ primary or second- ¦
ary amino groups at~ached ~o th~ po~ymsr lattic~D Co~mercially a~ailabl~ weak ba e anio~ exchangers inelude Dowex 37 Amberlit~ ¦
IR;459 ~e-Acidi~e G and Duolite ~-14~ Cellulo~e a~ion exchangers9 such as diekhylaminoQth~l-(DEAE~) and ep~chlorhydrin~triethanol amin~ (ECTEOLA-~ CellulOse9 may al.so be us~d in khe fractionation processc The po~itively char~e~ prstein hydroly~a~e fract~ons o~ this in~e~tion are rich in po~itlYely charged amino acid~
as determined by their high ~soionic pQi~S of about 7 ~o 11 whereas9 pro~eins presenkly i~ use commercially, have isoionlc points between 4 and 50 The hydroly~ed protein mix~ures from whlch present noval positi~ely charg~d protein hydrolysat~
~ract~ons ~re extracted, such a~ Lexe~n 100 P and Stepan PP 37, have isoionic pol~s o~ 4r~ and 4~3 respec~ively. The isoionic point (pI) i~ measured on a pro~ein which has been thoroughly ~ialyzed to ~ fr~o of all no~-colloidal ions~ It ls the pH of the pur~ pro~ein in dlstill~d wa~ara Pro~ein3 generally con~ain a m~xture of basic amine a~d imine group~ a~d acidic carbo~lic groups~ in ths form o~
basic and acidic amdno ac~ Pro~e~n~ rich in basic groups are more positiv01y ~harg~d and exhibit high pI valuasg wh~reas 'J l l prote~nR ricll in ncldic grours w~ e ]es~ ro~itlv~ly cllnr~oll and exhibit low pI values. The po~itive char~e8 are caused mainly by the arginine, lysine and histidine moieties. The negative charges are caused mainly by the aspartic and glutamic acid moieties. The overall charge is caused mainly by the ratio of the posltively charged moieties to the negatively charged ones. Ilence, a molecule rich in arginine, lysine and his~idine, and poor in aspartic and glutamic acid would have a high positive charg$. For example, glycylarginine has a positively charged group and no negatively charged group; therefore, its positive charge is very high (pI 11). In order to obtain a protein hydrolysate fraction which contains the compound glycylarginine, the protein hydrolysate should not be dialyzed prior to being contacted with the anion exchange resin because the glycylar- ¦
ginine would be removed along with the inorganic salts by pass-ing through the dialysis membrane. Ilowever, a high pI probably .
Lndicates a slgniflcant concentration of glycylargin.ine mo:Le~ies in the positively charged ion exchange fraction.
It has une~pectedly been found that a correlation exists between the anti-irritant propert:Les of these posltively charged proteins and their pI value as evidenced by Table I~
using vitro tests. The in vltro test measures the degree of curling of epidermis strips lmmersed ln test solutions, by measuring the width of the strip at its narrowest point where curling is most pronouneed. The aqueous test solutions contain 0.15~ SLS and 0.10% protein, adjusted to pll 5.3 and the strips are soaked therein at room temperature for two days prior to m~nsuring the narrowe~t part of the ep:ldermis strip.
` ~
I -12- 1 _ ~ ~L95~
TABLE I
Isoionlc ~ualitative C~rl POINT ~ I) Rankin~** Index~**
TEST MATERIAL
H20 - 1 1.01 SLS ~ Inolex Collagen Hydrolysate Fraction Al 8.7 2 0.78 SLS ~ Inolex Collagen Hydrolysate Fraction Bl 7.~ 3 0.64 SLS ~ Crotein Q* 10.0 4 0.61 SLS ~ Whole Inolex Collagen Uydrolysate Mixture 4.8 5 0.55 SLS ~ Inolex Collagen Hydrolysate Fraction c23,7 6 0.36 SLS 7 0.09 SLS + Inolex Collagen Hydrolysate Fraction23.5 8 0.21 *Crotein Q is manufactured hy Croda, Inc. New York,, NY
lt is a cationic quaternary derivative of hydrolyzed collagen proteln, more specifically described in Brochure 7778 of Croda, Inc.
**The lower the ranking number the more effective the protei~
in preventlng skin curling by SLS.
***Ratio of Half-height width of the stratum cor~leum to the ~nd wldtll; in general, the higher the numbcr the more effective th~ proteln ill preventing skin curling by SLS.
._ ~_ lA postively charged protein hydrolysate fraction obtalned by anion exchange oE dialyzed Lexein lOOP using BioRad AG 1 resin aceeate (50~100 mesh) at a specific pH followed by neutra1ization to pH 7, dialysis and lyophilization. Fraction A represents the filtrate obtained at pH 12; Fraction B repre-sents the filtrate obtained at pH 8. Neutralizations ~o pH 7 were made with dilute hydrochloric acid.
A negatively charged protein hydrolysate fraction obtained by anion exchaDge of dialyzed Lexein lOOP using BioRad AG 1 resin acetate ~50-100 mesh~ at a specific pH. Fractlon C
represents the material retained by the resin at pH 2; Frac~ion D represents the material retalned by the resin at pH 4.
Materials retained by the resin were removed using 2 Molar sodium chloride solution. Neutralizations to pH 7 were made wi~h dilute sodium hydroxide.
~13-~ ~ i6~
Sodlum lauryl sulfate (SLS~ itself causes severe curling . of the ep$dermis. When an Inionic protein fraction is added to the SLS, the protein ha~ no effect. However, when a cationic protein is added to SLS, the protein dramaticall~ counters the curling effect of the ~LS making thi~ strip of epidermis similar to a strip from a wa-ter treatment. Normally one would expect that positively charged proteins would inter~ct with negatively charged de^tergent molecule~l thereby destroying or reducing any mildnes~ ef~ect caused by the protein. In fact, surprisingly it iR enhanced~ Although the cationic proteins neutralize the effect that SLS has on in vitro epidermis9 no difference in ~oam height has been observedO Furthermore, the oation~c pro-teins actually stabilize the fo~ height~
~ he dentifrice contains an anionic ~urface active a~ent -to achieve increased prophylactic action and assist in achieving thorough and complete dispersion of the composition throughout th~ oral cavity. The anionio surface active agen-ts contain a sulfonat~, sulfate, carbox~late or phosphate as the anionic water ~301ubilizing group. Examples of suitable anionic deter-~ents include the soapY 9 such as the water soluble sal-ts of higher fatty acids or rosin acids9 such as may be derived from fats~ oils and waxes of animal9 ve~etable or marine origin, e.g., the sodium soaps o~ tallow, grease, coconut oil, tall oil and mixtures thereof; and the sulfated and sulfonated synthetic ` '' .
- ~ ~s~
detergents, particularly -those having about 8 to 26, and pre- ¦
ferably about 1~ to 22, carbon atoms to the molaculec ~xa~ )les of suitable synthetic anionic detergents include the higher alkyl mononuclear aromatic sulfonates such as the higher alkyl benzene sulfonates containing from 8 -16 carbon atoms in the alkyl group in a straight or branched chain, e.g. the sodiu~
salts of decyl, undecyl, dodecyl (lauryl), -tridecyl, -tetradecyl, pentadecyl, or hexadecyl benzene sulfonate and the C8-C16 al~yl toluene, xylene and phenol sulfonatesA ~-C16 alkyl naphtalene sul _ fonate, ammonium diamyl naphthalene sulfonate, and sodiwn di-nonyl naphthalene sulfona-te; sulfated alipha-tic alcohols such as sodiurn lauryl and hexadecyl ~ulfates, triethanolamine lauryl ~ulfate, and sodium oleyl sulfate; sulfated alcohol ethers, 9UCh as lauryl, tridecyl, or tetradecyl sul~ates includin~ l-S
ethylene oxide moieties; sulfated and ~ulfonated fatty oils, acids or esters, such as the sodium salts of sulfonated castor oil and sulfated red oil; sul~ated hydroxyamides such as 5Ul-f~ted hydroxy-ethyl lauramide; sodium salt of lauryl slAlfoacetate sodium salt of dioctyl sulfosuccinate, and the sodium salt of oleyl methyl tauride.
Also incIuded within the ambit of the invention are ~he s~' f ur i c id es t ers of l~olyhydr ic al ohol s in- mpl et ely ~15--- ~
~ 5~
esterified with higher fatty acidst e.gO, coconut oil monogly~
ceride monosulfate, tallow diglyceride monosulfate; and the hydroxy sulfonated higher fat-ty acid esters such as the hi~her fatty acid esters of low molecular weight alkylol sulfonic aeids, e.g~ oleic acid ester of isethionic a~eid.
The anionic surfactants most often used are the anunonium, mono-~ di- and triethanolamine, and alkali metal (sodium and potassium) sal-ts of -the hi~her alkyl banzene sulfonates 9 the higher allcyl sulfates, the higher fatty acid monoglyceride sul--fates and the sulfated ethoxylated alcohols and mixture~ thereof.
'roothpastes and toothpowders conventionally con-tain a substantially water insoluble polishing a~en-t or abrasive ~hich is compatible with the formulationO Particularly compatible materials include a for example, dicalcium phosphate dihydrate, dicalci~n phosphatc anhydrous, tricalciu~ phosphatep magne~ium c~lrbonate, c~lcium carbonate, calcium pyropho~phate, calcilln sulfate~ polymethylmethacrylate1 bentonite, etc.p and suitable mixtur~s thereor. Abr~sive r~sinous substances such as the condensation products of melamine and urea with forlnaldch~d~
ean ale,o be used~ It is preferred to use dicalc iUI;I ,.)I-O'~
dihydrate, dicalcium phosphate anhydrous, alld c~lciwll carboI1ate. 1 Tho poliJh r~ u~ollt mcy be the eolL ccrrior ~ tcrial cl-L i3 1, ,~
CF~'~. .
present in an amount up to about 95 percent of the carrier and generally about 20-75% of the carrier.
In toothpaste formulations the liquids and solids should necessarily be proportioned to form a creamy mass having the desired consistency which is extrudable from a pressurized container or a collapsible tube (for example, aluminum or lead).
In general, the liquids in the toothpaste will comprise chiefly water, glycerine, aqueous solutions of sorbitol, propylene glycol, polyethylene glycol 400, etc., and suitable mixtures thereof. It is advantageous usually to use a mixture of both water and a humectant or binder such as glycerine or sorbitol.
The total liquid content will generally be about 20-75% of the carrier. The amount of water is generally abut 10-25%, preferably about 12-17% of the carrier. It is preferred to also use a gelling agent in toothpastes such as the natural and synthetic gums and gum-like materials such as Irish moss, gum tragacanth, sodium carboxymethylcellulose, polyvinyl-pyrrolidone, starch, and the like, usually in an amount up to about 10%, and preferably about 0.2 to 5%, of the carrier.
The carrier suitably may contain a fluorine-containing compound having a beneficial effect on the care and hygiene of the oral cavity, for example, diminution of el~mel solu~ility in acid and protection of the teeth against decay. Examples thcreof include stannous fluoride, po-tassium stannous fluoride (SnF2KP), sodi~n hexafluorostannate, stannous chlorofluoride, sodium fluorozirconate, and sodium monofluorophosphate. l`hesc m~terials, whiGh dissociate or release fluorine contairlirl~ ions in water, suitably may be present in the carrier in an effcctive but nontoxic amount, usually within the range of about 0.1 to
amino acids or a qua~ernized hydrolyzed protein, having an isoionic point above 7 and a Bloom gel value of zero, to an anionic surface active agent-containing dentifrice counters the adverse reactions of said anionics which include reduced gingival inflammation, reduced sloughing of the oral mucosa, reduced bitterness of foods, reduced bitterness of the dentifrice itselfJ but surpri.singly not a con-comitant :Loss .in foaming power or detergency.
Accordingly, a primary object of present invention is to reduce the adverse ef:Eect that anionic surfactants in a dentifrice 1~ have on human oral tissue.
The present invention attempts to provide a substantially non-irritating dentifrice of improved flavor contai.ning an anionic surfactant and a positively charged partially hydrolyzed protein fraction rich in amino acids or a quaternized protein hydrolysate m:i~ture.
Pre:ferably, the dentifrice of the present invention has foaming and detergency properties of the aniollic surfactant which are not decreased by the presence of the water soluble posi.tively cl~ rgecl p~rt:i.ally hyd.rolyzed protein :fraction or the quaterni.zecl l~ydrolyzed protein.
6~
Additional, advantages and novel features of the inven-tion will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention.
In accordance with the present invention there is pro-vided a substantially non-irritating dentifrice composition compris-ing an anionic surfactant, and a water soluble positively charged partially hydrolyzed protein having an isoionic point above 7, and a Bloom gel value of zero, selected from the group consisting of a protein hydrolysate fraction containing a high concentrati.on of basic amino acids, and a quaternary derivative of the partially hydrolyzed protein, in a dental vehicle.
More specifically, present invention relates to a dentifrice composition, which may be in the form of a powder, paste or l:iquid, comprising an anionic sur:Eace active agent and about 0.2 - 5% of a positively charged partially hydrolyzed protein _~ ~ ~ ~S6~l~
~rac~ion contalning high conc~ntra~ion~ of ba~ic ami~o acids obtained by extraction from a partially hydroly~d protein mix-ture ~nd isolatiora by ion exchange ~r~atmen~ wi~h an a~ion exchange resin9 or a positive~r charged quaternized hydrolyæed protein, in a dental vehicl~0 The positively charged protein hydrolysat~ fraction utili~ed in present inven~ion con~ins a high eoncentration o~ ba~ic amino acids~ ha~ an isoioniG poin~ greater tha~ 7 ~nd a Bloom g~l value of æero; aI~d a molecular weight of about 600 to 12,000, and is a solid powdered water ~olubls mat~rial9 The positively charged quaternlze~ hydrolyzed pro~ein used in pres~nt lnve~tion i~ a catio~ic qua~ernary derivative of hyàrolyz~d collagen protein,, a product of Crnda IncO of New York, kno~n as Cro~ein Q~, having a m~ni~ pI of 905-1005, and is an off-white free flowing powder5, The free amlno groups in the protein molecul~ r~ac~ with the quater~a~ ammonium r~aat~n~ to ~orm the qua~arnized d~rivatlve,D
The positively chargad prot~in constltutes about 002 to 5~ and preferab~r 0~,7 ~o 1..3j~ by weight o.~ ~he dentifrice containing about 0~5 5% and pre.~erably 1~3~ by we~;h~ o:f an anioni~ surfactan~ Said positively charged pro~sins r~d~lc~
the oral irritation ~nd th- bitter fla~sr og~ the anionic sur~
119561'~
factant witihout decr~asi~g ~he :Eoaa~ng and d~ergenc~ properti~s I
of the compo~i~ioll5 The po~ikively eharged, partially hydroly~ed protein ~ractior~ having a high concen~ration of basic amino acids is prepar~d by ex~rac~ion from a ~lydroly~ed protei~ mix~ure and ~solakion o~ the pos~tivel~ charged fraction by mean~ of ion e~cchangz trea~men~ with a~ anio~ ¢xchange resi~., More specific~
ally~ said protei~ mixture i~ treated with an aniorl sxchang~
resi~i9 f`ollowed by dialy~is. The hydrol~sate fraction may be used as such or may op~ionally be fre~e dried ~o remove the water therefrom. The pro~ein mixtur~ may ~e an animal collageIa h~rdrolysat~, re~ultilig from ~ha hydrolysi~ o~ ~ protein with an acid or base or e~zyme. Wh~n th~ protei~ is hydrolyz~d by an acid or base9 i~ is n~cessary to remove ~ho salts (NaCl) ~ormed during sa.id hy~roly~is~ prior to treakment of said prow ~e~n h~droly~ata mix~ure with ~he ~Ilion exchallg~a resixi~ The ~alt~ can be removed b~r dialy~1~ of ~he pro~;ein hydro:lysate m:Lx-~ure., The ~our~e of the an:lmal collag~n hydro.~ysate may be lea~her ~crap~ pi~s :~ee~ a~ hoove~9 bollas3 skin or fee~ of E~ork or be~f~ Coms~lea~cial prod~ck~ suc~ as Sgelpan PP 37~ from StE3pa~ Chemical Co." Ghicago~ ïlli~oi~, a~ a~imal cellag~ ¦
h~drol~sa~e hydrolyæed at high pH (~a~OH32) ~ro~ l~ath~r ~craps,o, ' ~I/D~D
1, _ _ S631 ~
and Lexein lO0 P from Inolex Corporation, Chicago, Illinois, an animal collagen hydrolysate from pigs feet and hooves, hydro-lyzed by means of steam and/or acid followed by enzyme treatment, are typical collagen protein mixtures from which the positively charged protein hydrolysate fractions may be extracted and iso-lated.
More specifically, the process of preparing the posi-tively charged protein hydrolysate fraction containing a high concentration of basic amino acids comprises the steps of treat-~0 ing a partially hydrolyzed protein mixture with an anionexchange resin to absor~ negatively charged groups from the pro-tein onto the resin and to substitute acetate groups or other negative]y charged groups therefor on the resin and dialyzing the resultant anion-exchanged protein hydrolysate fraction to remove said resin-substituted negatively charged groups. A pre-ferred additional first step comprises dialysis of the hydrolyzed protein mixture prior to treatment with the anion exchange resin .in order to remove salts and other impuri-ties which may be present as a result of protein hydrolysis. ~n optionally adcli-t.ional fi.na]. step comprises Ereeze drying the positively chargedprotein h~drolysate ~raction to remove the water therefrom and res~rve it for Euture use. Ion exchange chromatography is a well lcncwn procedure described in the prior art. The batch phase ion exchange chromatography procedure for separation of proteins, based on charge, is described in an article by S.M. Vratsanos and I.D. ~andel entitled "Isolation of Cationic Salivary Proteins"
in the Journal of Dental ~esearch, Volume 56, B109, special i~sue B, 1977.
* trade mark g ~$~j~
The column ion exchange chromatography method is described in a 1973 brochure by Pharmacia entitled "Sephadex Ion Exchangers ~ A Guide to Ion Exchange Chromatography". The optimal ratio of ion exchange resin -to protein for fractionation of a hydrolyzed pro-tein mixture by ion exchange Ghromatography is approximately 20:1. This represents the ratio of resin to protein required to just absorb the anionic proteins onto the resin, but not absorb the neutral or cationic proteins.
Any suitable anion exchange resin may be utilized in the process of producing the positively charged protein hydroly-sate fractions containing a high concentration of basic amino acids. The polystyrene- and polysaccharide-based anion exchang~
ers are most often used. The most important class of anion-exchange resins is based on the introduction of basic groups such as ~uaternary amino groups into a styrene-divinylbenzene copolymer a~ter polymerization. These are strongly basic anion exchange resins. E~amples of strong base anion exchangers are Dowex 1 and 2 resins by Dow Chemical Companyr Amberlite IR~
~01 and 410 resins of Rohm and Haas Company, De-Acidite FF and Duolit~s ~-40 and ~ ~2 oE Diamond Shamrock Company and Bio-Rad 1 resin of Bio-* trade mark ~, .., i ~ ! ' ' 9 5 ~
Rad Company~ Wea~ bas~ anion exchangers haY~ primary or second- ¦
ary amino groups at~ached ~o th~ po~ymsr lattic~D Co~mercially a~ailabl~ weak ba e anio~ exchangers inelude Dowex 37 Amberlit~ ¦
IR;459 ~e-Acidi~e G and Duolite ~-14~ Cellulo~e a~ion exchangers9 such as diekhylaminoQth~l-(DEAE~) and ep~chlorhydrin~triethanol amin~ (ECTEOLA-~ CellulOse9 may al.so be us~d in khe fractionation processc The po~itively char~e~ prstein hydroly~a~e fract~ons o~ this in~e~tion are rich in po~itlYely charged amino acid~
as determined by their high ~soionic pQi~S of about 7 ~o 11 whereas9 pro~eins presenkly i~ use commercially, have isoionlc points between 4 and 50 The hydroly~ed protein mix~ures from whlch present noval positi~ely charg~d protein hydrolysat~
~ract~ons ~re extracted, such a~ Lexe~n 100 P and Stepan PP 37, have isoionic pol~s o~ 4r~ and 4~3 respec~ively. The isoionic point (pI) i~ measured on a pro~ein which has been thoroughly ~ialyzed to ~ fr~o of all no~-colloidal ions~ It ls the pH of the pur~ pro~ein in dlstill~d wa~ara Pro~ein3 generally con~ain a m~xture of basic amine a~d imine group~ a~d acidic carbo~lic groups~ in ths form o~
basic and acidic amdno ac~ Pro~e~n~ rich in basic groups are more positiv01y ~harg~d and exhibit high pI valuasg wh~reas 'J l l prote~nR ricll in ncldic grours w~ e ]es~ ro~itlv~ly cllnr~oll and exhibit low pI values. The po~itive char~e8 are caused mainly by the arginine, lysine and histidine moieties. The negative charges are caused mainly by the aspartic and glutamic acid moieties. The overall charge is caused mainly by the ratio of the posltively charged moieties to the negatively charged ones. Ilence, a molecule rich in arginine, lysine and his~idine, and poor in aspartic and glutamic acid would have a high positive charg$. For example, glycylarginine has a positively charged group and no negatively charged group; therefore, its positive charge is very high (pI 11). In order to obtain a protein hydrolysate fraction which contains the compound glycylarginine, the protein hydrolysate should not be dialyzed prior to being contacted with the anion exchange resin because the glycylar- ¦
ginine would be removed along with the inorganic salts by pass-ing through the dialysis membrane. Ilowever, a high pI probably .
Lndicates a slgniflcant concentration of glycylargin.ine mo:Le~ies in the positively charged ion exchange fraction.
It has une~pectedly been found that a correlation exists between the anti-irritant propert:Les of these posltively charged proteins and their pI value as evidenced by Table I~
using vitro tests. The in vltro test measures the degree of curling of epidermis strips lmmersed ln test solutions, by measuring the width of the strip at its narrowest point where curling is most pronouneed. The aqueous test solutions contain 0.15~ SLS and 0.10% protein, adjusted to pll 5.3 and the strips are soaked therein at room temperature for two days prior to m~nsuring the narrowe~t part of the ep:ldermis strip.
` ~
I -12- 1 _ ~ ~L95~
TABLE I
Isoionlc ~ualitative C~rl POINT ~ I) Rankin~** Index~**
TEST MATERIAL
H20 - 1 1.01 SLS ~ Inolex Collagen Hydrolysate Fraction Al 8.7 2 0.78 SLS ~ Inolex Collagen Hydrolysate Fraction Bl 7.~ 3 0.64 SLS ~ Crotein Q* 10.0 4 0.61 SLS ~ Whole Inolex Collagen Uydrolysate Mixture 4.8 5 0.55 SLS ~ Inolex Collagen Hydrolysate Fraction c23,7 6 0.36 SLS 7 0.09 SLS + Inolex Collagen Hydrolysate Fraction23.5 8 0.21 *Crotein Q is manufactured hy Croda, Inc. New York,, NY
lt is a cationic quaternary derivative of hydrolyzed collagen proteln, more specifically described in Brochure 7778 of Croda, Inc.
**The lower the ranking number the more effective the protei~
in preventlng skin curling by SLS.
***Ratio of Half-height width of the stratum cor~leum to the ~nd wldtll; in general, the higher the numbcr the more effective th~ proteln ill preventing skin curling by SLS.
._ ~_ lA postively charged protein hydrolysate fraction obtalned by anion exchange oE dialyzed Lexein lOOP using BioRad AG 1 resin aceeate (50~100 mesh) at a specific pH followed by neutra1ization to pH 7, dialysis and lyophilization. Fraction A represents the filtrate obtained at pH 12; Fraction B repre-sents the filtrate obtained at pH 8. Neutralizations ~o pH 7 were made with dilute hydrochloric acid.
A negatively charged protein hydrolysate fraction obtained by anion exchaDge of dialyzed Lexein lOOP using BioRad AG 1 resin acetate ~50-100 mesh~ at a specific pH. Fractlon C
represents the material retained by the resin at pH 2; Frac~ion D represents the material retalned by the resin at pH 4.
Materials retained by the resin were removed using 2 Molar sodium chloride solution. Neutralizations to pH 7 were made wi~h dilute sodium hydroxide.
~13-~ ~ i6~
Sodlum lauryl sulfate (SLS~ itself causes severe curling . of the ep$dermis. When an Inionic protein fraction is added to the SLS, the protein ha~ no effect. However, when a cationic protein is added to SLS, the protein dramaticall~ counters the curling effect of the ~LS making thi~ strip of epidermis similar to a strip from a wa-ter treatment. Normally one would expect that positively charged proteins would inter~ct with negatively charged de^tergent molecule~l thereby destroying or reducing any mildnes~ ef~ect caused by the protein. In fact, surprisingly it iR enhanced~ Although the cationic proteins neutralize the effect that SLS has on in vitro epidermis9 no difference in ~oam height has been observedO Furthermore, the oation~c pro-teins actually stabilize the fo~ height~
~ he dentifrice contains an anionic ~urface active a~ent -to achieve increased prophylactic action and assist in achieving thorough and complete dispersion of the composition throughout th~ oral cavity. The anionio surface active agen-ts contain a sulfonat~, sulfate, carbox~late or phosphate as the anionic water ~301ubilizing group. Examples of suitable anionic deter-~ents include the soapY 9 such as the water soluble sal-ts of higher fatty acids or rosin acids9 such as may be derived from fats~ oils and waxes of animal9 ve~etable or marine origin, e.g., the sodium soaps o~ tallow, grease, coconut oil, tall oil and mixtures thereof; and the sulfated and sulfonated synthetic ` '' .
- ~ ~s~
detergents, particularly -those having about 8 to 26, and pre- ¦
ferably about 1~ to 22, carbon atoms to the molaculec ~xa~ )les of suitable synthetic anionic detergents include the higher alkyl mononuclear aromatic sulfonates such as the higher alkyl benzene sulfonates containing from 8 -16 carbon atoms in the alkyl group in a straight or branched chain, e.g. the sodiu~
salts of decyl, undecyl, dodecyl (lauryl), -tridecyl, -tetradecyl, pentadecyl, or hexadecyl benzene sulfonate and the C8-C16 al~yl toluene, xylene and phenol sulfonatesA ~-C16 alkyl naphtalene sul _ fonate, ammonium diamyl naphthalene sulfonate, and sodiwn di-nonyl naphthalene sulfona-te; sulfated alipha-tic alcohols such as sodiurn lauryl and hexadecyl ~ulfates, triethanolamine lauryl ~ulfate, and sodium oleyl sulfate; sulfated alcohol ethers, 9UCh as lauryl, tridecyl, or tetradecyl sul~ates includin~ l-S
ethylene oxide moieties; sulfated and ~ulfonated fatty oils, acids or esters, such as the sodium salts of sulfonated castor oil and sulfated red oil; sul~ated hydroxyamides such as 5Ul-f~ted hydroxy-ethyl lauramide; sodium salt of lauryl slAlfoacetate sodium salt of dioctyl sulfosuccinate, and the sodium salt of oleyl methyl tauride.
Also incIuded within the ambit of the invention are ~he s~' f ur i c id es t ers of l~olyhydr ic al ohol s in- mpl et ely ~15--- ~
~ 5~
esterified with higher fatty acidst e.gO, coconut oil monogly~
ceride monosulfate, tallow diglyceride monosulfate; and the hydroxy sulfonated higher fat-ty acid esters such as the hi~her fatty acid esters of low molecular weight alkylol sulfonic aeids, e.g~ oleic acid ester of isethionic a~eid.
The anionic surfactants most often used are the anunonium, mono-~ di- and triethanolamine, and alkali metal (sodium and potassium) sal-ts of -the hi~her alkyl banzene sulfonates 9 the higher allcyl sulfates, the higher fatty acid monoglyceride sul--fates and the sulfated ethoxylated alcohols and mixture~ thereof.
'roothpastes and toothpowders conventionally con-tain a substantially water insoluble polishing a~en-t or abrasive ~hich is compatible with the formulationO Particularly compatible materials include a for example, dicalcium phosphate dihydrate, dicalci~n phosphatc anhydrous, tricalciu~ phosphatep magne~ium c~lrbonate, c~lcium carbonate, calcium pyropho~phate, calcilln sulfate~ polymethylmethacrylate1 bentonite, etc.p and suitable mixtur~s thereor. Abr~sive r~sinous substances such as the condensation products of melamine and urea with forlnaldch~d~
ean ale,o be used~ It is preferred to use dicalc iUI;I ,.)I-O'~
dihydrate, dicalcium phosphate anhydrous, alld c~lciwll carboI1ate. 1 Tho poliJh r~ u~ollt mcy be the eolL ccrrior ~ tcrial cl-L i3 1, ,~
CF~'~. .
present in an amount up to about 95 percent of the carrier and generally about 20-75% of the carrier.
In toothpaste formulations the liquids and solids should necessarily be proportioned to form a creamy mass having the desired consistency which is extrudable from a pressurized container or a collapsible tube (for example, aluminum or lead).
In general, the liquids in the toothpaste will comprise chiefly water, glycerine, aqueous solutions of sorbitol, propylene glycol, polyethylene glycol 400, etc., and suitable mixtures thereof. It is advantageous usually to use a mixture of both water and a humectant or binder such as glycerine or sorbitol.
The total liquid content will generally be about 20-75% of the carrier. The amount of water is generally abut 10-25%, preferably about 12-17% of the carrier. It is preferred to also use a gelling agent in toothpastes such as the natural and synthetic gums and gum-like materials such as Irish moss, gum tragacanth, sodium carboxymethylcellulose, polyvinyl-pyrrolidone, starch, and the like, usually in an amount up to about 10%, and preferably about 0.2 to 5%, of the carrier.
The carrier suitably may contain a fluorine-containing compound having a beneficial effect on the care and hygiene of the oral cavity, for example, diminution of el~mel solu~ility in acid and protection of the teeth against decay. Examples thcreof include stannous fluoride, po-tassium stannous fluoride (SnF2KP), sodi~n hexafluorostannate, stannous chlorofluoride, sodium fluorozirconate, and sodium monofluorophosphate. l`hesc m~terials, whiGh dissociate or release fluorine contairlirl~ ions in water, suitably may be present in the carrier in an effcctive but nontoxic amount, usually within the range of about 0.1 to
5~ by weight.
Various other rnaterials may also be incorporated into the carr~er. ~xamples thereof are coloring or whiterlin~ a~ents (for example, titaniwn dioxide), preservatives (for example, sodium benzoa-te), silicones, chlorophyll compounds~ al~noniated m~lterials sucn as ure~, diar.lmonium phosphate, and mixturc3 thereof, alcohol, menthol~ and other constituents. Thesc adju-val~ts arc incorporated irlto the in3t~mt colnpo~itiorls in ;l;;10UrltS' which do not subst~ltially adversely affect the propertics ~nd ch~racteristics and ar~ suitably selectcd arld used in proper amount depending upon the par-ticular type of preparations involved.
' I
~ ~ ~5~
Flavoring or sweetening materlals of the type commonly employed in dentifrices may be included in the carrier. Such materials, if present, aid in modifying the particular tastes of the flavor in the manner desired. Examples of such addi-tional materials include the flavoring oils, for example, oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, and orange, as well as methylsalicylate~ Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, sodium cyclamate, and saccharin.
~0 Suitably, the flavor and sweetening agent may together comprise about 0.01 to 2.0% of the carrier.
The dentifrice may be prepared by suitably mixing the ingredients. For instance in making a toothpaste, a gelling ayent such as sodium carboxymethyl cellulose or Carbopol 93 and a preservative such as sodium benzoate, if employed, is dispersed in a humectant such as glycerine. Water may also be present. Additional humectant and water may then be mixed with the dispersion and a homogeneous paste, ~el or cream is formed.
Dental abrasive agent, surface active agent and flavor are then .D ~clcl~. The toothpaste is then thoroughly deaerated (e.g., in * trade mark ,, -- 19 --~L195619 . I
vacuo) and tubed. The formulation may be deaerated during mixing or after mixing.
~=~
l l The following examples are merely illustrative of the invention, but it is understood that the invention is not - ¦
limited thereto. All amounts of various ingredients are by weight unless otherwise specified.
Dicalcium phosphate dihydrate 50 50 50 Glycerine 20 20 20 .
~lo:lex ll'raotion A (pI 8.7) 1 _ _ Crotein Q
Cellulose g~lm 1~0 loO 1~0 Sodium monofluorophosphate 0076 0~76 0~76 . -20 ~L~L95~ii9 ~ I ~ I
_ _ :
Flavor 00 ~ 0~ ~ O. ~
Te~rasodium pyrophospha~e 0~25 0025 0~.25 Sodium saccharin 0"2 0,.2 0"2 Sodium laur;yl sulfate With water Q~S~ Q~,S. Q.,S.
Orange ~uice ~ests on the aboYe ~ormulatiorls, wherei~
the taste of oraIIge juice was assessed before and after brushing with the dentifa~ice ~or~ulation ga~e th~ :~ollowing r~sults., Orang~ juica had a p:Lea~aIlt tas~e prior to bru~hing w:lth the d~ntifric!l of Example 3,, but a sour or bitter taste after brushing with Example 3 which is a flavor~d forDlula~iQnl, HowQver~ a~t~r brush:lng with the proteirl contalning compositions of ~campl~ 1 and ~ ~le 2? the taste was ~Nch improved, i.e~ ¦
b~ r~ .
Example~; 19 2 a~ld 3 w~re al~o tasted in the absence of orange juice and comparedO ~cample 3" with no protein~ was li more bitter than Exampl~ 1 and 2~ ~
Xt was additionally found that ~he protei~ contsir~ g . , I
~:~L9S~
dentifrice exhibited thre0 tim~s a~ much foaming as the non prot~in de~l~ifrice., variakio~s i21 ~oothpast~ formulations 1 and 2 may bs made by u~ilizing 0-5~,g cellulo~e gum~ 0-5~ sodium fluorophosphate9 ~5~ flavor~ 0-5~o tetrasodi~ pyrophospha~e a~ ~; sodium saccharin~ hout adversely affeG~ing the beneficial properties as to tasto, foaming and no~ irritancy of ~he pro~ein-contai3ling dentifrice~
. . I
.
~ ~ .
~alcium pyrophospha~e 94~3 Sodium lauryl sulfate 3~0 S~annous Fluoride 0~, 5 Flavor 1,2 Inolex Frackion A (pI ~07) 1.0 .
aa~
' ' U~
:
~22 ^
, - ,1 ll ~35~
Sodium lauryl sulfa~e ~,0 Flavor . 2 ~ 3 Color l-S
Sodium saccharin 0. 5 Powd~red Iri~h moss 1G25 Inolex Frac'cion A ( pl ~ ,9 7 )1 ID O
J ;thyl alcohol lOe O
Water Q~, X~D ¦
Variation~ in the above formulatio~s may b~ madeO For cxampl~? o~her anionic ~urfactants such as higher alkyl be~zene sulfonate~, fatty ~cid soaps ~uch as tallow soap, sulfated alco-hol e~hers and the like may be substituted for the sp~cific an~onic su~factant~ in the examplss.
I.ikewls~l other posltlvely char~sed prokeirl hydrolysa~e îractiox~s having a p~ above 7 and obtained ~rom other collagen h:y~rolysate ~ource~ may be substikut~d ~or the particular fra^tion used ~n ~he examples~ ~
Other thickening or gelIing agen~ ca~ b0 subs~itu~ed for the cellulose gum of th~ examples~ Similarl~3 oth~r con--ventional den al abra~ive~ can replace ths ,icaloium phosphate .' _ ~ -23-.
',, 'J
~ 35 abrasive such a~ calclum pyrophosphat~" insolubls sodium meta~
phoqpha~e and the likeO O~her f~orinec contair~ing compounds can be substitutQd for the mono~luorophospha~e such as sodium îluoride~ potas~ium fluoride9 s~aDnous fluoride and the likeO
It is undsrstood tha~ the foregoing d~tailed descriptlo~
is given m~rely by way o~ ~Lllustratior~ d ~ha~ variations may be ~ad~ therein without depar~ing from tha spir~t o~ the illYen- ¦
tiOIl~. The 'IAbstract'l given abov~ is m~rely for the convenienc0 of technical searche2~3 and is no~ to b~ given ~lly weight with rospeot to t u scope Or the invention.
I ~ ~
l ~' l
Various other rnaterials may also be incorporated into the carr~er. ~xamples thereof are coloring or whiterlin~ a~ents (for example, titaniwn dioxide), preservatives (for example, sodium benzoa-te), silicones, chlorophyll compounds~ al~noniated m~lterials sucn as ure~, diar.lmonium phosphate, and mixturc3 thereof, alcohol, menthol~ and other constituents. Thesc adju-val~ts arc incorporated irlto the in3t~mt colnpo~itiorls in ;l;;10UrltS' which do not subst~ltially adversely affect the propertics ~nd ch~racteristics and ar~ suitably selectcd arld used in proper amount depending upon the par-ticular type of preparations involved.
' I
~ ~ ~5~
Flavoring or sweetening materlals of the type commonly employed in dentifrices may be included in the carrier. Such materials, if present, aid in modifying the particular tastes of the flavor in the manner desired. Examples of such addi-tional materials include the flavoring oils, for example, oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, and orange, as well as methylsalicylate~ Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, sodium cyclamate, and saccharin.
~0 Suitably, the flavor and sweetening agent may together comprise about 0.01 to 2.0% of the carrier.
The dentifrice may be prepared by suitably mixing the ingredients. For instance in making a toothpaste, a gelling ayent such as sodium carboxymethyl cellulose or Carbopol 93 and a preservative such as sodium benzoate, if employed, is dispersed in a humectant such as glycerine. Water may also be present. Additional humectant and water may then be mixed with the dispersion and a homogeneous paste, ~el or cream is formed.
Dental abrasive agent, surface active agent and flavor are then .D ~clcl~. The toothpaste is then thoroughly deaerated (e.g., in * trade mark ,, -- 19 --~L195619 . I
vacuo) and tubed. The formulation may be deaerated during mixing or after mixing.
~=~
l l The following examples are merely illustrative of the invention, but it is understood that the invention is not - ¦
limited thereto. All amounts of various ingredients are by weight unless otherwise specified.
Dicalcium phosphate dihydrate 50 50 50 Glycerine 20 20 20 .
~lo:lex ll'raotion A (pI 8.7) 1 _ _ Crotein Q
Cellulose g~lm 1~0 loO 1~0 Sodium monofluorophosphate 0076 0~76 0~76 . -20 ~L~L95~ii9 ~ I ~ I
_ _ :
Flavor 00 ~ 0~ ~ O. ~
Te~rasodium pyrophospha~e 0~25 0025 0~.25 Sodium saccharin 0"2 0,.2 0"2 Sodium laur;yl sulfate With water Q~S~ Q~,S. Q.,S.
Orange ~uice ~ests on the aboYe ~ormulatiorls, wherei~
the taste of oraIIge juice was assessed before and after brushing with the dentifa~ice ~or~ulation ga~e th~ :~ollowing r~sults., Orang~ juica had a p:Lea~aIlt tas~e prior to bru~hing w:lth the d~ntifric!l of Example 3,, but a sour or bitter taste after brushing with Example 3 which is a flavor~d forDlula~iQnl, HowQver~ a~t~r brush:lng with the proteirl contalning compositions of ~campl~ 1 and ~ ~le 2? the taste was ~Nch improved, i.e~ ¦
b~ r~ .
Example~; 19 2 a~ld 3 w~re al~o tasted in the absence of orange juice and comparedO ~cample 3" with no protein~ was li more bitter than Exampl~ 1 and 2~ ~
Xt was additionally found that ~he protei~ contsir~ g . , I
~:~L9S~
dentifrice exhibited thre0 tim~s a~ much foaming as the non prot~in de~l~ifrice., variakio~s i21 ~oothpast~ formulations 1 and 2 may bs made by u~ilizing 0-5~,g cellulo~e gum~ 0-5~ sodium fluorophosphate9 ~5~ flavor~ 0-5~o tetrasodi~ pyrophospha~e a~ ~; sodium saccharin~ hout adversely affeG~ing the beneficial properties as to tasto, foaming and no~ irritancy of ~he pro~ein-contai3ling dentifrice~
. . I
.
~ ~ .
~alcium pyrophospha~e 94~3 Sodium lauryl sulfate 3~0 S~annous Fluoride 0~, 5 Flavor 1,2 Inolex Frackion A (pI ~07) 1.0 .
aa~
' ' U~
:
~22 ^
, - ,1 ll ~35~
Sodium lauryl sulfa~e ~,0 Flavor . 2 ~ 3 Color l-S
Sodium saccharin 0. 5 Powd~red Iri~h moss 1G25 Inolex Frac'cion A ( pl ~ ,9 7 )1 ID O
J ;thyl alcohol lOe O
Water Q~, X~D ¦
Variation~ in the above formulatio~s may b~ madeO For cxampl~? o~her anionic ~urfactants such as higher alkyl be~zene sulfonate~, fatty ~cid soaps ~uch as tallow soap, sulfated alco-hol e~hers and the like may be substituted for the sp~cific an~onic su~factant~ in the examplss.
I.ikewls~l other posltlvely char~sed prokeirl hydrolysa~e îractiox~s having a p~ above 7 and obtained ~rom other collagen h:y~rolysate ~ource~ may be substikut~d ~or the particular fra^tion used ~n ~he examples~ ~
Other thickening or gelIing agen~ ca~ b0 subs~itu~ed for the cellulose gum of th~ examples~ Similarl~3 oth~r con--ventional den al abra~ive~ can replace ths ,icaloium phosphate .' _ ~ -23-.
',, 'J
~ 35 abrasive such a~ calclum pyrophosphat~" insolubls sodium meta~
phoqpha~e and the likeO O~her f~orinec contair~ing compounds can be substitutQd for the mono~luorophospha~e such as sodium îluoride~ potas~ium fluoride9 s~aDnous fluoride and the likeO
It is undsrstood tha~ the foregoing d~tailed descriptlo~
is given m~rely by way o~ ~Lllustratior~ d ~ha~ variations may be ~ad~ therein without depar~ing from tha spir~t o~ the illYen- ¦
tiOIl~. The 'IAbstract'l given abov~ is m~rely for the convenienc0 of technical searche2~3 and is no~ to b~ given ~lly weight with rospeot to t u scope Or the invention.
I ~ ~
l ~' l
Claims (10)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A substantially non-irritating dentifrice composition comprising an anionic surfactant, and a water soluble positively charged partially hydrolyzed protein having an isoionic point above 7, and a Bloom gel value of zero, selected from the group consisting of a protein hydrolysate fraction containing a high concentration of basic amino acids, and a quaternary derivative of the partially hydrolyzed protein, in a dental vehicle.
2. A dentifrice according to claim 1, wherein the posi-tively charged protein hydrolysate constitutes about 0.2 - 5% by weight of the composition.
3. A dentifrice according to claim 2, wherein the anionic surfactant constitutes about 0.5 - 5% by weight of the composi-tion.
4. A dentifrice according to claim 1, containing a posi-tively charged partially hydrolyzed protein fraction having a high concentration of basic amino acids, prepared by extraction from a hydrolyzed protein mixture and isolation of the positively charged fraction by means of ion exchange treatment with an anionic exchange resin to absorb negatively charged groups from the protein mixture.
5. A dentifrice according to claim 1, containing a quater-nary derivative of hydrolyzed collagen protein.
6. A dentifrice according to claim 1, in the form of a toothpaste containing a liquid content of about 20 - 75% by weight of the composition.
7. A dentifrice according to claim 1, containing about 20 - 75% by weight of a water insoluble abrasive.
8. A dentifrice according to claim 1, containing about 0.2 - 5% by weight of a gelling agent.
9. A dentifrice according to claim 1, containing about 0.1 - 5% by weight of a fluorine-containing compound.
10. A dentifrice according to claim 1, wherein the anionic surfactant is sodium lauryl sulfate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US357,918 | 1982-03-15 | ||
| US06/357,918 US4391798A (en) | 1982-03-15 | 1982-03-15 | Non-irritating dentifrice |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1195619A true CA1195619A (en) | 1985-10-22 |
Family
ID=23407567
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000423485A Expired CA1195619A (en) | 1982-03-15 | 1983-03-14 | Non-irritating dentifrice |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4391798A (en) |
| JP (1) | JPS58189108A (en) |
| AU (1) | AU558812B2 (en) |
| CA (1) | CA1195619A (en) |
| CH (1) | CH654203A5 (en) |
| DE (1) | DE3308523A1 (en) |
| FR (1) | FR2522965B1 (en) |
| GB (1) | GB2118835B (en) |
| IT (1) | IT1165582B (en) |
| PH (1) | PH17454A (en) |
| ZA (1) | ZA831587B (en) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4428929A (en) | 1983-03-04 | 1984-01-31 | Wicheta William E | New oral cleansing medium for wearers of partial and full dentures |
| ZA853905B (en) * | 1984-06-12 | 1986-12-30 | Colgate Palmolive Co | Stable dentifrice containing dextranase |
| US5000939A (en) * | 1984-06-12 | 1991-03-19 | Colgate-Palmolive Company | Dentifrice containing stabilized enzyme |
| PH23397A (en) * | 1985-12-11 | 1989-07-26 | Unilever Nv | Oral hygiene product |
| JPS62223115A (en) * | 1986-03-25 | 1987-10-01 | Rooto Seiyaku Kk | Remedy for periodontosis |
| LU86586A1 (en) * | 1986-09-15 | 1988-04-05 | Oreal | TOOTHPASTE CONTAINING A POLY NON-IONIC SURFACTANT (HYDROXYPROPYLETHER) AND A DETERMINED CATIONIC POLYMER |
| US5043154A (en) * | 1987-01-30 | 1991-08-27 | Colgate-Palmolive Co. | Antibacterial, antiplaque, anticalculus oral composition |
| US5080887A (en) * | 1987-01-30 | 1992-01-14 | Colgate-Palmolive Company | Antibacterial antiplaque, anticalculus oral composition |
| US5174989A (en) * | 1987-11-25 | 1992-12-29 | Shiseido Company Ltd. | Oral composition |
| EP0554297B1 (en) * | 1990-10-25 | 1995-04-12 | The Boots Company PLC | Mouthwash |
| US5120528A (en) * | 1991-06-12 | 1992-06-09 | Block Drug Company, Inc. | Taste preserving, mild oral hygiene compositions |
| US5374418A (en) * | 1992-02-13 | 1994-12-20 | Kao Corporation | Composition for use in oral cavity |
| US5370865A (en) * | 1992-05-15 | 1994-12-06 | Kao Corporation | Composition for use in oral cavity |
| US5292502A (en) * | 1992-07-02 | 1994-03-08 | Colgate-Palmolive Co. | Non-irritating dentifrice |
| US5741773A (en) * | 1996-04-26 | 1998-04-21 | Colgate Palmolive Company | Storage stable dentifrice composition containing an antibacterial casein glycomacropeptide adjuvant |
| DE10049656A1 (en) * | 2000-10-07 | 2002-04-11 | Henkel Kgaa | Improving the foaming properties of an aqueous tooth-paste by addition of a plant protein hydrolysate or its condensation product with a 12-22C fatty acid |
| ES2178953B1 (en) * | 2000-12-20 | 2003-09-16 | Sl Para El Desarrollo Cientifi | DENTIFRIC PRODUCT. |
| DE10253217A1 (en) * | 2002-11-15 | 2004-05-27 | Cognis Deutschland Gmbh & Co. Kg | Use of quaternized protein hydrolyzates in washing and cleaning agents |
| US20070183986A1 (en) * | 2006-02-06 | 2007-08-09 | Ultradent Products, Inc. | Methods and systems for mixing a multi-part fluoride varnish composition |
| US7776010B2 (en) * | 2006-05-01 | 2010-08-17 | Ultradent Products, Inc. | Syringe-in-syringe hollow inner barrel/plunger with integral seal and rupturable membrane and related kits, systems, and methods |
| US8454558B2 (en) | 2007-02-09 | 2013-06-04 | Ultradent Products, Inc. | Syringe-in-syringe hollow inner barrel/plunger with integral seal and rupturable membrane and related kits, systems and methods |
| US8383163B2 (en) * | 2008-01-29 | 2013-02-26 | Ultradent Products, Inc. | Fluoride varnish compositions including an organo phosphoric acid adhesion promoting agent |
| CN102378621A (en) | 2009-04-02 | 2012-03-14 | 高露洁-棕榄公司 | Exfoliating dentifrice composition and method of use |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR737220A (en) * | 1931-09-03 | 1932-12-08 | Henkel & Cie Gmbh | Toothpaste and oral hygiene product |
| US2236828A (en) * | 1936-01-11 | 1941-04-01 | Colgate Palmolive Peet Co | Dental cream |
| GB551369A (en) * | 1940-06-11 | 1943-02-19 | Conrad Lawrence Walsh | Improvements in the manufacture of toilette preparations and the like |
| US2812284A (en) * | 1953-04-15 | 1957-11-05 | Procter & Gamble | Oral detergent composition and dentifrice comprising same |
| US3256155A (en) * | 1962-04-11 | 1966-06-14 | Lever Brothers Ltd | Dentifrice composition |
| CA807629A (en) * | 1966-06-30 | 1969-03-04 | Eigen Edward | Lotion and detergent compositions |
| FR6721M (en) * | 1967-06-13 | 1969-02-17 | ||
| US3839590A (en) * | 1970-02-02 | 1974-10-01 | Avicon Inc | Cosmetic compositions containing microcrystalline collagen,a water-insoluble,ionizable,partial salt of collagen |
| JPS4925337B1 (en) * | 1970-03-31 | 1974-06-29 | ||
| US4058596A (en) * | 1971-10-13 | 1977-11-15 | Colgate-Palmolive Company | Stabilized toothpastes containing an enzyme |
| US4195077A (en) * | 1974-01-18 | 1980-03-25 | The Procter & Gamble Company | Detergent compositions comprising modified proteins |
| US4076800A (en) * | 1975-01-13 | 1978-02-28 | The Procter & Gamble Company | Protein-containing detergent compositions for protecting keratinous materials |
| ZA773318B (en) * | 1976-06-18 | 1978-04-26 | I Kleinberg | Means and method for improving natural defenses against caries |
| DE2712228A1 (en) * | 1977-03-19 | 1978-09-28 | Georg Dr Leiderer | Protein hydrolysate from collagen by strong acid hydrolysis - useful as additive for tooth-pastes, textile and hair washing compsns. |
| US4130555A (en) * | 1977-09-06 | 1978-12-19 | Nippi Incorporated | Peptide mixtures derived from collagenous material or gelatin |
| JPS6035507B2 (en) * | 1978-09-21 | 1985-08-15 | 株式会社大林組 | Shear reinforcement method for openings in reinforced concrete members |
| DE3011618A1 (en) * | 1980-03-26 | 1981-10-01 | Württembergische Parfümerie - Fabrik GmbH, 7332 Eislingen | TOOTH CREAM WITH HIGH FOAM RESISTANCE |
-
1982
- 1982-03-15 US US06/357,918 patent/US4391798A/en not_active Expired - Fee Related
-
1983
- 1983-03-08 ZA ZA831587A patent/ZA831587B/en unknown
- 1983-03-10 DE DE19833308523 patent/DE3308523A1/en not_active Withdrawn
- 1983-03-14 CA CA000423485A patent/CA1195619A/en not_active Expired
- 1983-03-14 AU AU12440/83A patent/AU558812B2/en not_active Ceased
- 1983-03-14 PH PH28643A patent/PH17454A/en unknown
- 1983-03-15 GB GB08307103A patent/GB2118835B/en not_active Expired
- 1983-03-15 IT IT47909/83A patent/IT1165582B/en active
- 1983-03-15 CH CH1428/83A patent/CH654203A5/en not_active IP Right Cessation
- 1983-03-15 JP JP58043020A patent/JPS58189108A/en active Granted
- 1983-03-15 FR FR8304227A patent/FR2522965B1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2522965B1 (en) | 1987-06-26 |
| FR2522965A1 (en) | 1983-09-16 |
| GB2118835B (en) | 1986-01-22 |
| GB2118835A (en) | 1983-11-09 |
| IT8347909A0 (en) | 1983-03-15 |
| IT1165582B (en) | 1987-04-22 |
| JPS58189108A (en) | 1983-11-04 |
| AU558812B2 (en) | 1987-02-12 |
| DE3308523A1 (en) | 1983-09-29 |
| PH17454A (en) | 1984-08-29 |
| GB8307103D0 (en) | 1983-04-20 |
| US4391798A (en) | 1983-07-05 |
| CH654203A5 (en) | 1986-02-14 |
| JPH0259803B2 (en) | 1990-12-13 |
| AU1244083A (en) | 1983-09-22 |
| ZA831587B (en) | 1984-10-31 |
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