Download UNITED STATES

Patented Jan. 16, 1934
1,943,467
UNITED STATES PATENT OFFICE
_
1,943,467
PHARMACEUTICAL PREPARATION
Rudolph S. Bley; Washington, D. O.
No Drawing. Application February 8, 1932v
Serial No. 591,755
1.8 Claims. (Cl. 167-93) '
This invention‘relates to an improved anti
1
pounds exert a more powerful germicidal effect
septic dentifrice. I am well aware that numerous than those used up to date in dentifrices.
antiseptics have been already incorporated into
‘
In my copending applications I have claimed a
dentifrices as a means to check pyorrhuea process of producing reaction products of all
5 alveolar-is, a dental disease of bacterial origin. phatic and aromatic acids with monohydric, di
However all these well-known antiseptics are hydric and trihydric phenols.
highly poisonous to animal tissue especially to
By condensng carboxylic or fatty acids of the
the tender mucous membranes, and it is for this type CnH2n+1.(COOI-I):c with monohydric, di—
reason that all of these antiseptics can be used mrdric or trihydric phenolsin presence of con
10 only in very small percentages in dentifrices, densing agents such as zinc chloride and reduc
thus decreasing greatly their germicidal value. ing the intermediate reaction product with zinc
The phenol coef?cient of most of the well-known amalgam, powerful antiseptics oi’ the following 70'
dentifrices is therefore extremely low.
structure are evidently obtained.
The primary object of the present invention
15 is to incorporate into dentifrices antiseptics of i
such type which are non-poisonous to human wherein It represents a hydroxybenz‘ene. The
beings even when swallowed in small quantities. CnH2n+1 radical may be evidently linked to the
Another object of the present invention is to benzol nucleus in the ortho, meta or para posi
incorporate into dentifrices a highlyconcentrated.
2o antiseptic or a mixture of highly concentrated
By condensing for example caproic acid with m
antiseptics without having any harmful effect diphydroxybenzene and reducing the 1,3-dioxy
tion.
upon human teeth and their surrounding tis
.
sues.
_
A further object of this invention is to incorpo
25 rate into dentifrires such antiseptics which are
I
up
'
phenyl-lA-alkylketones, n-hexyl-2,4-dihydroxy
80
benzene is ?nally obtained. The puri?ed, crys
talline reaction product is soluble in‘ water, alco
hol or ether. It has a speci?c gravity of about
characterized by a low surface tension, thus in 1.282, a melting point of about 116° C. and a boil
creasing the property of penetration of said anti ing point of about 276° 0. Its phenol coe?iclent
septics into the cavities of teeth and tissues is 45-55 and its surface tension in aqueous solu
to which such dentifrices are applied. Anti
tion 35-40 dynes per centimeter. By condensing
30 septics of low surface tension penetrate readily other fatty acids with m-dihydroxybenzene and
small crevices and spaces which may harbour reducing the intermediates, a series of ?nal re
microorganisms and moreover they diduse into action compounds may be obtained for example: 90
bacterial cells more readily, thus more rapidly
C-propionyl-m- dihydroxybenzen?e.
destroying the same. Under equivalent condi
C-butyl-m-dihydroxybenzene.
35 tions the efficiency of a germicide is increased the
C-heptyl-m-dihydroxybenzene.
more its surface tension is reduced. Dentifrices
C-octyl-m-dihydroxybenzene.
95
having incorporated therein compounds of low
surface tension are characterized by a better
wetting property which promotes the cleansing
40 action of such dentiirices.
u
l have discovered that reaction products of
C-dodecyl-m-dihydroxybenzene.
C-isobutyl-m-dihydroxybenzene.
C-isoamyl-m-dihydroxybenzene.
C-isohexyl-m-dihydroxybeiizene, etc.
aliphatic and aromatic acids with monohydric, Instead of m-dihydroxybenzene, o-dihydroxy 100
dihydric and‘trihydric phenols exert a powerful benzene or p-dihydroxybenzene may be used to
germicidal action and that they are harmless produce ortho and para compounds respectively.
4.5 to animal tissue even in concentrated form.
Such~ reactions may also be carried out with
When swallowed in small quantities by human hydroxybenzenes or trihydroxybenzenes.
beings they are non-poisonous, but on the con
Instead of reacting aliphatic acids with hy 105
trary some of these compounds, especially n
droxybenzenes and reducing the intermediates,
hexyl-m-dihydroxy-benzene, have a bene?cial ef
aromatic acids may be reacted upon in a similar
60 feet upon the urinary organs when the same are
infected by bacilli of the Coli group.
I prefer to use such reaction products as in
gredients in dentifrices which have a low surface
tension in order to increase the germicidal co
“ efficient of such dentifrices. However I wish to
state that satisfactory results may also be ob
manner.
.
.
‘
I have moreover found that especially hetero
cyclic compounds of the furane group yield reac
.110
tion‘ products with hydroxybenzenes which are
splendid antiseptics for dentifrices.
. .
By condensing for example furoic acid or py
romucic acid with hydroxybenzenes and reducing
the intermediate products, preferably in "statu 115
tained with reaction compounds which do not nascendi”, ?nal reaction products having high
have a very low surface tension. Even such com phencl coef?cients are obtained.
17,048,467
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saponins, quinine, quinine derivatives,
Two isomers are evidently obtainable having‘ starches,
glucosides, peppermint oil, peppermint‘ oil sub
probably the following structures:
, (1) alpha-furfurylhydroxybenzenes:
,
stitutes, clove oil, eucalyptol, terpenyl acetate.
cassia oil, cinnamon oil, thyme oil, nutmeg oil,
anethol, camphor, eugenol, phenethyl alcohol,
H/ xHJI
Caraway oil, orris root powder, alcohols, berga
mot oil, rose-geranium oil, neroli oil, citronellol,
HIS-J11.
benzaldehyde. ‘albumins, myrrh powder, menthol,
methyl, salicylate, thymol, geraniol, ‘lavender oil,
lemon oil, citral, cosine, salol, phloxine, magenta
crystas, erythrosine, sodium-benzoate, carmine,
saffron, glycerine, glycerine of starch, glycerine
wherein It represents a \hydr
(2) beta-furfurylhyroxybenzenes:
10
substitutes, honey, syrup, molasses, lrevulose,
gums, vitamins, irradiated vitamins, radioactive
sébstances,
15 wherein R represents also a hydroxybenzene.
'
e
ferments, bu?er salts,
. . . .
About 2-100% of the finely ground antiseptic
Evidently the furane nucleus may be linked to is added to'the dentifrices as follows. The addi
the benzol nucleus in theortho, meta or para tion of enzymes may vary between l/4--5 per
position.
‘ '
thousand; though more of the same may be in 95
A further object of my invention is to incorpo
20 rate my antiseptics together with enzym_ , for corporated at will.
Example 1: Acid tooth powder
example diastase, into dentifrices. I am aware
that it has been already proposed to use enzymes,
for example pepsin, in dentifrices. Enzymes
Cream of tartar-.. _______________ _i__ 400 grams 100
have also been combined with certain antiseptics,
Kieselguhr ............ _.'. _________ _- 600 grams
25 ' such as thymol, alcohol, phenol, etc.. without de
Erythrosine ______________________ __ 0.5 grams
creasing their activity considerably. However
Oilof peppermint ________________ __
10 cc.
all these antiseptics mustbe used in very dilute
form, otherwise enzymic action is inhibited.
I have found that antiseptics produced by re
30 acting aliphatic or aromatic acids upon hydroxy
benzenes and reducing the intermediates in the
described manner do not inhibit enzymic action‘
' even when added to enzymes in concentrated
35 form.
Citral ____________________________ __
1.5 cc.
N-hexyl-m-dihydroxybenzene for example in
Antiseptic-- 2-100 per thousand of the total mix 135
Example 2: Alkaline toothpowder
sodium bicarbonate ___________ _-_-_-
50 grams
Borax
50 grams
Magnesium carbonate ............ _- 400 grams 111)
Precipitated chalk _____________ _,__ 500 grams
Eucalyptol ____________________ Q...
5 cc
50% aqueous solution does not decrease the en Terpenyl acetate _______________ -zymic action of diastase upon carbohydrates, such Soluble saccharine ______________ .3.
as starches. By incorporating, for example,
diastase in its natural-or isolated form together
40 with n-hexyl-m-dihydroxybenzene into a denti
frice, a splendid commer
product is obtained.
The antiseptic ingredient instantaneously kills
pathogenic microorganisms without aifecting the
‘
5 cc.
1 g.
Antiseptic __________________ _- as in Example 1‘ 115
Example 3: Antacid toothpowder
Precipitated chalk ________________ -_ 700 grams
um carbonate ____________ __ 225 grams
tissue, its germicidal action being greatly s\ip—‘ Borax ___________________________ __
45 ported by its low surface tension. The diastatic Eosine ___________________________ __
oil ________________________ _.
ingredient, on the other hand, rapidly hydrolizes Cassia
,
oil
starchy food particles clinging to crevices and ‘Rose
120
75 grams
1 g.
8 cc.
2
cc.
__________________ _- as in Example 1
cavities of teeth or vtheir surrounding tissues. Antiseptic
By this hydrolysis soluble and digestible sugars Diastase at will; preferably V4-5 per thousand 125,
50 are obtained. Such a dentifrice has not only‘
Example 4: Saponaceous toothpouider
high germicidal, but also therapeutical proper
Powdered castile soap _____________ __ 200 grams
ties.
My antiseptics may be used in combination Chalk precipitated _______________ __ 400 grams 13o
with neutral, alkaline, acid‘or foaming denti Magnesium carbonate _______ __._.'-___ ‘400 grams
frices.
Gluside (600) ____ -._ ______________ _- ‘
“
1 g.
I wish to point out that r am not limited to Peppermint oil ___________________ _.. 1 cc.
speci?c tooth paste combinations, but my anti Lemon oil ______________________ _-__ 9 cc.
septics may be added to any known commercial Antiseptic as in Example 1 or antiseptic plus dias- 135
tooth paste composition. They may be combined
60 , also with dry tooth powders or antiseptic chew
gums.
_
tase as in Example 3
.
Example 5: White toothpaste
As a base for tooth powders or tooth pastes I Precipitated chalk. _______________ __ 500 grams
65
may use: precipitated chalk, amorphous prepared Tricalcium orthophosphate ________ .. 400 grams
chalk, calcium phosphate, kieselguhr, clay, kao Soluble saccharine?m ____________ __ 0.5 g. .
lin, magnesium carbonate, pumice, cattle ?sh Soap powder....__';._-_ ______________ __'100 g.
bone, strontium oxide, soap, catechu, tin oxide, Tragacanth
-_
1 g.
barium sulphate, camphorated chalk, charcoal.
zinc oxide, zinc carbonate, etc. . . . In other words,
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I may use any inorganic or organic base known
in the tooth paste art.
Peppermint oil ___________________ __
Spearmint oil __________ __.. _______ __
Methyl salicylate _________________ __
5 g.
1 g.
2 g.
140
V
145
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‘
honey,
Other modifying and ?avoringcompounds may Clari?ed
proper consistency
be incorporated, such as cream of tartar, sodium Antiseptic or antiseptic plus enzyme as in Ex
bicarbonate, borax, saccharine, sodium chloride,
ampleslanda
boric ‘acid, milk sugar, glucose, higher sugars,
150
3
Example 6; Pink toothpaste
6. An antiseptic dentifrice which does not dele
Add to composition, Example 5, proper amount teriously affect animal tissue comprising a fur
furyl-m-mrdroxybenzene andan enzyme in active
of erythrosine or the like
state.
I wish to point out that the above examples are
7. A dentifrice comprising n-hexyl-m-dihy
merely illustrative, and I do not wish to be limited. droxybenzene and active diastase.
_
to the exact proportions set forth above, which
8. A composition of matter comprising a con
are typical combinations, as certain of these in
gredients may be omitted or replaced by others
10 of similar nature, and the proportions within
limits may be varied. In other words, while I
have found that the ingredients and proportions
above mentioned give the desired results, I do not‘
wish to be limited to the use of all of these in
15 gredients, to these ingredients and no others,
nor to the exact proportions and concentrations
set forth above, as the omission of some ingre
dients or a slight variation of proportions will
centrated solution of an antiseptic and an enzyme
in active state suspended therein, said antiseptic
having the structure R.CnH:n+1.‘wherein R repre
sents a hydroxybenzene.
9. A composition of matter comprising a con
centrated solution of a furfuryl-hydroxybenzene
which acts as a disinfectant and an enzyme in
active state dispersed therein.
10. The method of preserving the activity of
enzyme suspensions which comprises adding
thereto ?nal, reaction products. which are not
not adversely affect the ?nal dentifrice, although deleterious to animal tissue, of an aliphatic acid
20 it may vary somewhat the relative characteristics with a hydroxybenzene having probably the struc
95
of such dentifrice. resulting from such variations. ture R.CnH2n+1, wherein R represents a hydroxy
Moreover I wish to point out that I may combine
one or more different types of my antiseptics in
benzene.
'
11. The method of preserving the activity of
one dentifrice. with other words I may combine, enzyme suspensions which comprises . adding
25
for example the hexyl-m-dihydroxybenzene with thereto final reaction products of an aromatic 100
the furi'uryl-m-dihydroxybenzene etc. . . ., to acid with a hydroxybenzene having probably the
obtain the desired germicidal action.
structure R.R1, wherein R1 represents a phenyl
What I claim and desire to secure by Letters radical and R a hydroxybenzene.
‘
12. The method of preserving the activity of
1. An antiseptic dentifrice, which does not enzyme suspensions which comprises adding 105'
30
deleteriously affect animal tissue comprising ?nal thereto ?nal reaction products of a furane deriva
Patent is:
reaction products of organic acids with hydroxy tive with a hydroxybenzene. '
benzenes and an enzyme in active state.
13. The method of preserving the activity of
2. An antiseptic dentifrice which does not dele diastase suspensions which comprises, adding
35 teriously affect animal tissue comprising a ?nal thereto hexyl resorcinol.
"
110
reaction product of an aliphatic acid with a hy
14. The method of preserving the activity of
droiwbenzene, having probably the structure enzyme suspensions which comprises adding
R.CnH:n+1, wherein R represents a hydroxyben thereto hexyl resorcinol.
zene and an enzyme in active state.
40
15. The method of preserving the activity of
3. An antiseptic dentifrice which does not dele enzyme suspensions which comprises adding 115
teriously affect animal tissue comprising a ?nal thereto a furfuryl-m-Mdroxybenzene.
reaction product of an aromatic acid with a hy
16. The method of preserving the activity of
droxybenzene, having probably the structure diastase which comprises adding thereto furfuryl
BB1, wherein R represents a hydroxybenzene, R: m-dihydroxybenzene.
a phenyl radical, and an enzyme in active state.
17. A composition of matter comprising an 120
4. An antiseptic dentifrice which does not dele alkylresorcinol which acts as an antiseptic and an
teriously affect animal tissue comprising a ?nal enzyme in active state dispersed therein.
reaction product of a furane derivative with a
18. A composition of matter comprising
hydroxybenzene and an enzyme in active state.
alkylresorcinol and active diastase. ‘
'
5. An antiseptic dentifrice which does not dele
125
teriously affect animal tissue comprising n-hexyl
m-ghydroxybenzene and an enzyme in active
LRUDOLPH 8. BLEY.
135.
no
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