Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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TOPICP.L PREPARATION FOR TREATING HERPES SIMPLEX VIRUS
Technical Field
The present invention relates to a method for txeat-
ing Herpes simplex virus and to a top$cal preparation for
application to areas of the human body infected by ~erpPs
simplex virus for inactivating the virus.
Background Art
There are two types of Herpes simplex vlrus which
produce a variety of clinical manifestations. In general,
Herpes simplex type 1 is associated with recurrent labial-
i5 scold sores and Herpes simplex type 2 is associated
with recurrent vulvovaginitis.
Herpes simplex virus appears to find the spongy
area around mucus membranes an attractive place to thrive
and cause infectivity. Once the integrity of an area is
violated by Herpes simplex virus, there seems to be a
triggering mechanism that welcomes repeated infection of
the same area The reason for this phenomenon occurring
is not known at present.
Herpes simplex virus infectivity is primarily de-
pendent upon the intactness of the viral envelope and a
chemical combination which damages or removes the envelope
will reduce infectivity greatly. It is well known that
ether is extremely successful in producing this effect.
However, the normal body temperature is about 4C above
the boiling point of ethyl ether such that treatment in
vivo heretofore has not been successful. See for example
"Topical Ether and Hexpes Simplex Labialis" by Mary E.
Guinan, M.D., Ph.D., et al. JAM, March 14, 1980, Vol. 2~3,
No. 10, pp. 1059-61. Also, due to the extxeme instability
of ether, particularly ethyl ether, at room temperature
or higher ethyl ether has heretofore only been used for
this type of treatment in a controlled environment such as
a hospital or physician's office, and ethyl e~hex has not
been available in a form sultable for use outside of a
controlled (e.g., hospital) environment.
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Rather, ether-, amide-, or ester-linkage compounds,
alone or in combination, have been used. However, the
effectiveness of such compounds in treating Herpes simplex
virus is far lest thin that of a pure ether. An example
of an emulsion including such a compound is disclosed in
the Asculai et alO U.S. Patent No. 4,020,183.
According to the teachings of this patent, non-
ionic surfactants are delivered in a non-irritating car-
rier such as a lotion or oil to an infected area with the
amount of surfactant employed being between 0.5% and 20
by volumeO
It has also been proposed in Alnor U.S. Patent No.
3,949,071 to use an aqueous solution including a base,
fatty acids comprising primarily oleic acid, and a surface-
active agent for treating burns, scalds and other skin ir-
rita~ions. The base is an alkali metal carbonate.
Further it has been proposed in Grove U.S. Patent
No. 2,0~9,166 to use a topical preparation of a soft soap
and stearoptens in a salve for use as a liniment.
Still further it is known from "A simple proof of
the thermodynamic stability ox materials taken up by solu-
tions containing solubilizers such as soup", Amer. Chem.
Soc. 62, 2855-9 (1940) that ether is thermodynamically
stable in soap. More specifically, the colloidal solutions
formed from a solution of ther and soap containing small
additions of silicate or hydroxide are thermodynamically
stable because the vapor pressure is significantly less
than that of the free hydrocarbon until the solution is
approximately saturated.
Moreover, it is known from SOAP MANUFACTURE by J.
Davidsohn, et al. published by Interscience Publishers, Inc.
New York, p. 495, that coconut oil soap was germicidally
more active against Escherichia coli and Eberthella typhosa
than other soaps made from natural fats and oils. Also,
this text teaches at page 503 that coal tar soaps can be
made by adding wood tar to coconut oil soap and at page
505 that sulphur soap can be made by adding sulphur to
coconut oil soap.
I
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As will be descried in greater detail hereinafter,
the method and topical preparation of the present invention
differ from the previously proposed method and preparations
in that according to the method of the preen inventlon
topical preparation comprising an emulsion of anhydrous
ethyl ether (rather than a linkage compound) wherein the
amount of anhydrous ethyl ether used comprises at least
30% by volume of the emulsion and a coconut oil caxrier is
applied to the infected area. Also, the emulsion uses a
coconut oil carrier having a minimum of free fatty acids.
Additionally, the method preferably includes the step of
subsequently applying heat to the infected area.
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DISCLOSURE OF INVENTION
According to the invention there is provided a
topical preparation for treating an epidermal area of a
human being infected with Herpes simplex virus character-
ized by comprising a stable emulsion havinq from approx-
imately 30~ by volume to approximately 50% by volume of
anhydrous ethyl ether in a pharmaceutically acceptable
oil carrier having most of the free fatty acids thereof
removed, said emulsion having a boiling point of at least
100F.
Further according ot the invention there is provi-
ded a method for treating in vivo an epidermal area of
a human being infected with Herpes simplex virus charac-
terized by comprising the step of applying to the infec-
ted area in an amount sufficient to cover the infectedarea a topical preparation including a stable emulsion
having from approximately 30~ by volume to approximately
50~ by volume of anhydrous ethyl ether in a pharmaceut-
tally acceptable oil carrier having most of the free
fatty acids removed, said emulsion having a boiling point
of at least 100F.
Preferably, heat is applied to the infected area
shortly after the topical preparation is applied, e.g.,
heat is applied for a period of between 3 and 15 minutes
approximately three minutes after the topical preparation
is applied.
Preferably, the pharmaceutically acceptable oil
carrier is coconut oil.
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BEST MODE FOR CARRYING OUT THE INVENTION
In accordance with the teachings of the present in-
vention, a topical preparation including an emulsion of
anhydrous ethyl ether end a coconut oil carrier having
most of the free fatty acids removed has been found to
be useful in treating epidermal areas infected with Herpes
simplex virus.
According to the method of the present invention a
stable emulsion of at least 30~ by volume of anhydrous
ethyl ether in a pharmaceuticallv acceptable coconut oil
carrier with most of the free fatty acids removed is ap-
plied to the infected area. Preferably, heat is also ap-
plied to the infected area some time after the application
of the topical preparation for a period of 3 to 15 minutes.
l It has been known for some time that ethyl ether is
very helpful in treating the "cold sore" lesion in an epi-
dermal area infected by Herpes simplex virus. In this re-
spect~ the ether damages or removes the viral envelope
thereby reducing infectivity. However, ether, particularly
ethyl ether, is extremely unstable and has a very low boil-
ing point. Accordingly, one must be very careful in apply-
ing ethyl ether and in the past this has only been done in
a controlled environment such as in a hospital outpatient
ward or in a physician's office. Also, the ethyl ether
evaporates quickly and as a result does not penetrate deep-
ly into the infected area.
In view of the rapid evaporation of ether, it has
been proposed in U.S. Patent NoO 4,020,183 to apply an
ether-linkage compound in a non-irritating carrier such as
a lotion or oil to the infected area. In this way the
ether-linkage compound in the carrier can be maintained
on the infected area for a significant period of time to
allow penetration by the ether-linkage compound. However,
the ekher~linkaga compound iB no as strong and efective
as ethyl ether in destroying the viral envelope.
Ihus, according to the teachings of the present in-
vention, anhydrous ethyl ether which is a highly volatile
chemical, is utilized. However, it must be combined with
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a carrier so that it will be more stable. Anhydrous ethyl
ether is used because it is believed to afford deeper pene-
tration than other ethers or ether linkage compounds hav-
ing a higher boiling point. Also, ethyl ether is more
S readily available for use in the anhydrous form than are
other ethers such as methyl ether, which has a lower boil
ing point. Anhydrous ethyl ether has virtually no (0 01%)
waxer. Thus, by using anhydrous ethyl ether, the infeo~ed
area is kept as dry as possible. In this respect, moistuxe
appears to be a d~terent to the healing process of the "cold
sore" lesion in an area infected with Herpes simplex virus
when applying ether thereto.
The anhydrous ethyl ether utilized in the method of
the present invention has the following American Chemical5 Society specifications:
Butylated Hydroxy-toluene (preservative) 0.5-1 ppm
Assay (C2H5)2 o by CC 98.5%
Color (APHA) 10
Density (gm/ml at 25C Max) .7079
20 Peroxide (as H202) .0001
Residue after evaporation .001
Substances darkened by H2S04 Passable
Alcohol (C2H50H) .01%
H20 (Karl Fisher) .01
~5 Trace I~lpurities PPM
Acid (as CH3C00~) .5
Copper .1
Heavy metals (A5PB~ .1
Nickel (Nlj .1
Further according to the teachings ox the present
invention, coconut oil with most of the free fatty acids
removed is used as the carrier. Although other natural
oils could be used, coconut oil was found to be the most
suitable for emulsification with the anhydrous ethyl ether.
The coconut oil can be refined and bleached or hydro-
genated.
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The refined and bleached or hydrogenated coconut
oil carrier is obtained in the following manner:
First, coconut oil is refined with caustic soda
(NaOH), this process also being known as refining of a
glyceride. Here the natural oil (a glyceride) is broken
down into glycerol and a soap containing most (at least
95~) of the free fatty acids. The glycerol is .retained
and this process of removing free fatty acids found in
the oil (i.e., palmitic, capric, oleic, linoleic and lino-
lenic acids) makes the carrier much less irritating tothe skin. The oil now contains no more than 7~ free fat-
ty acids and preferably between 2.5 and 3.5% free fatty
acids. It is believed that the refined coconut oil car-
rier aids in healing the epidermal area around the "cold
sore" lesion, which area has been leached of moisture by
the anhydrous ethyl ether applications, by sealing that
epidermal area to air and water which can be deterents to
the healing process.
After the refining, the glycerol is further pro-
cessed, i.e., it can be hydrogenated, to produce stearic
acid (cold cream) and the desired product, refined and
hydrogenated coconut oil, the carrier used in the emulsion
with the anhydrous ethyl ether. It has been found empir-
ically that the most suitable refractive index of hydro-
25 genation for the carrier is 1.4540 0.0002 at 25C and aniodine value of 4 5 0.5.
Refining and hydrogenation of oils are well known
processes and the manner in which these processes are carried
out is described in the text entitled: Official and
Tentative Methods of the Americ _ Oil Chemist's Society
(3rd Ed.) 1976, published by the American Oil Chemist's
Society, Champaign, Ill. In this text, refining of oil
techniques are described in A.O.C.S. Official Method Cc
8d-55 pages 1-3 and hydrogenation of oil techniques are
described in A.O.C.S. Recommended Practice Ca 17-~6 pages
1-3.
.
8 ~2~2~0
This hydrogenation process is believed to 510w down
the development of rancidity of the oil, a common problem
of oil based compounds and thus allows a longer shelf and
use life.
Refined and bleached or hydroyenated coconut oil
which has an iodine value of 4.5 0,5, which has no more
than 7% free fatty acids (FFA as oleic) and which has a
refractive index of 1.4540 1 0.0002 at 25~C is commercial-
ly available from:
CPC International
International Plaza
P.O. Box 500
Englewood Cliffs, N.J.,
frQm its subsidiary
sest Foods
CPC International
2841 S. Kilbourne
Chicago, Illinois
and from-
Capital City Products
1200 Route 46
W. New York, N.J.
One preferred partially hardened refined and bleached
(or hydrogenated) coconut oil had the following material
specifications:
Color (Lovibond) Max. 4.0 Red
F.F.A. (as oleic) Max. 7.0
M~I.U. (Moisture Inert:Dist) Max. 1.0
Saponification value Min. 254
(1) Polyunsaturated Acids Max. 0.40%
Iodine Value 4.5 + 0.5
Odor Usual characteristic odor
refractive index 1~4540 0.0002
(lo To be determined by using A.O.C.S. Method Cd 7-58
In the refining of the coconut oil, the free fatty
acids are taken off, i.e., the free fatty acids are conver-
ted to soap which settles and are taken off as "foots"
with glycerols of other fatty acids retained, I
the glycerols C6 to Cl8. The hydrogenation thus chan-
ges the unstable glycerols, e.g., oleic (unstable to ste-
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aric (stable).
Coeonut oil is a mixture of fatty acids of evennumber mole~ulte~ C6 through cl8_1~ The amount ox C6
and C20 are nil.
The distribution is as follows:
Fatty Acid %
C6 ~Caproic) Nil
C8 (Caprylic) 6+1
C10 (capric) 7+1
10 C12 Laurie 48. 5+10 5
C14 (Myristic~ 19.0il.0
C16 (Palmitic) 8.75~ 0.75
C18 tstearic) 5.25+ 0.75
C18_1 (Oleic) 3.00~ 0.50
15 The free fatty acids in the coconut oil will sapon-
ify under certain conditions during the refining of the
crude coconut oil while tha other components will not.
For example, in one refining process, 500 gm of
crude coconut oil is put into a water bath with a mechani-
cal stirrer at a temperature between 30-35C at 250 RPM.
Next an amount of ~0 Baume NaOH is added to effectively
saponify the free fatty acids, e.g., C17Il33COO~ (oleic
acid + NaOH = C17H33COONa -I H2O. The molecular weight ox
the oleic acid is 282.4 and the molecular weight of the
sodium hydroxide is 40.
After the amount of NaOH is determined by conven-
tional calculations, it is added to the water bath which
is then stirred for 5 minutes. Next, decrease speed to
70 RPM and raise the temperature of the water bath quick-
ly to 50-53C. Stir for 10-15 minutes more or until the
"foots" (bottom soap) appeax to be ready to settle out.
Let sit in bath until oil is relatively clear before re-
moving the refined oil.
In bleaching the refined coconut oil, a 60 mush
screen, bleaching earth as per American Oil Chemists
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Society standards,filter paper (Sargent Welch Grade
S 32915-J or equivalent) and rolled cotton are used.
The screen is lined with thin layers of rolled cotton
and 300 gm of refined oil are allowed to filter into a
stainless steel cup which is then placed under a mechan-
ical stirrer. Then, 9 grams of bleaching earth are added
and stirred at a temperature of 100 Jo 110C. The speed
of stirring is fast enough to keep the bleach in suspen-
sion for five minutes. Next the solution is filtered
through a steel funnel having the filter paper therein and
the filtrate of refined and bleached coconut oil is col-
lected in a beaker.
The emulsion of anhydrous etheyl ether and the hy-
drolyzed and hydrogenated coconut oil or the refined and
bleached coconut oil is combined in a ratio of from 1:2
to 1:1, anhydrous ethyl ether by volume to coconut oil
by volume with a ratio of 2.3 being preferred.
From numerous tests it was found that by combining
the coconut oil with the anhydrous ethyl ether in a ratio
of 3:2 by volume, forming thereby a supersaturated emul-
sion, the normal boiling point of the emulsified ethyl
ether is raised to approximately 119F. This numerical
ratio combination of the oil and ether was also observed
to produce the least amount of damage, i.e., necrosis, of
the viable tissue surrounding the herpetic lesion, while
still providing a highly effective agent in destroying the
viral envelope.
The emulsion is applied as a topical preparation to
the infected area or areas in an amount sufficient to cov-
er the infected area or areas once a day for a period offrom one week up to ninety days, if necessary. Empirical
measurements indicate that the amount applied is approxi
mately one cubic centimeter (1 cc1 for approximately each
each 1/4 square inch ~0.4 square centimeter) ox in~cted
surface area. More specifically, the preparation is ap-
plied daily until the "cold sore" lesions in the infected
area are no longer visible.
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Preferably, heat is also applied Jo the infected
area, and it has been observed that the heat application
appears to speed up and assist the healing process, i.e.,
the disappearance of the "cold sore" lesions.
Two types of heat ha been used with goods results.
One is radiant, infra-red or dry heat and the other is wet
heat applied with a hot, wet towel.
The radiant, infra-red heat is applied at a temper-
ature as high as the patient can withstand for a period
of lS to 20 minutes on the morning after the preparation
is applied. The infra-red source is positioned 16 inches
or rnore from the infected area on the patient's face with
a mask provided over the adjacent facial area, particular-
ly over the eyes, to protect them The radiant heat ap-
pears to assist in drying the lesions and was found to bevery effective in drying multiple eruptions.
It is also believed that thP application of heat in-
creases the blood supply to the area of infection and in-
creases oxygenation of the tissue in that area so as to
aid healing further. Also, increased blood flow caused
by application of heat is believed to promote a more rapid
removal of the debris left behind as the lesion is destroyed.
As an alternative to infra-red heat, wet heat in
the form of hot, wet towels can be applied to $he infec-
ted area at a temperature as high as the patient can with-
stand, for a period of 15 to 20 minutes each morning and
each evening with the topical preparation being applied
only once a day in the evening.
For individuals subject to multiple infections at
regular intervals, the topical preparation is applied three
times daily for the first five days followed by applica-
tion of the topical preparation three times a day for the
next five days with each such application being followed
by application of a hot, wet towel (as hot as the indiv-
idual can stand) for 3 to 20 minutes three times a day.
12 3~
In one method of treatment, about 2 cc of the top-
ical preparation is applied to the infected area around,
for example, the lipsD After tnree minuteC~ a wet towel,
as hot as is bearable by the patient, is applied to the
area for about the minute.
It is believed that without heat the ether pene-
trates the infected area as deeply as possible in about
three minutes. Then it is believed the heat from the wet
towel causes the ether what has penetrated to vaporize
allowing it to propel or move up the "trigeminal canal",
killing the viruses that hide there in a dormant state
and become active later causing recurrent infections.
Again, it is believed that about three minutes is a suffi-
cient time to keep the vapors moving in the canal at a suf-
ficient pressure and volume to destroy the virus.
Empirical studies show that one method of treatmentis to apply the topical preparation at least once (prefer-
ably twice) a day for three days. Then, on the third day,
even if the "cold sore" appear to be "cured", the prepar-
ation ancl heat as described above are applied three timesa day for at least three days. It is believed that after
this period the medication has "won the fight" in killing
the virus at the site of infection and the body's immune
system can take over the "battle" forcing the virus to
escape via the trigeminal canal.
I~o individuals who had had on the average one "cold
sore" per year during thy two years prior to treatment with
the method of the present invention were treated with a
topical preparation which comprised 60% by volume coconut
oil with most of the fatty acids removed and 403 by volume
anhydrous ethyl ether and which was applied to the infected
area once a day for seven days together with application
of radian, infra-red heat once a day on the morning after
application of the topical preparation. No recurrence of
the "cold sore" lesion was observed for a period of seven
years after this treatment.
Eight individuals who had had on the average four
"cold sore" lesions per year during the ten year period
,,
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13
prior to treatment with the method of the present inven-
tion were treated with a topical preparation which com-
prised 60~ by volume coconut oil with most of the fatty
acids removed and 40% by volume anhydrous ethyl ether
s and which was appiied to the infected area once a day
for ninety days together with applicat:ion of wet heat by
means of hot, wet towels twice a day for ninety days. Sub-
sequent to this treatment, no recurrence of the "cold sore"
lesions was observed for a period of 2 1/2 years after
treatment. The severity of infection with these individu-
als was such that on the average two of the four appear
ances of "cold sore" lesions were multiple lesions.
Another four individuals who had had on the average
five "cold sore" lesions per year during the ten years pre-
ceeding treatment with the method of the presetn inventlonwere treated with a topical preparation which comprised
60~ by volume of coconut oil with most of the fatty acids
removed and 40% by volume of anhydrous ethyl ether and
which was applied to the infected area once a day for nine-
ty days toge-ther with application of wet heat by means of
hot wet towels twice a day for ninety days. The severity
of the infection with these individuals was such that on
the average four out o five appearances of the "cold sore"
lesions were multiple lesions. No recurrence of the "cold
sores" was observed in these individuals for a period of
two years after treatment.
Still another ten individuals who had had on the
average two "cold sore" lesions per year during the ten
years prior to treatment with the method of the present in-
vention were treated with a topical preparation which com-
prised 60~ by volume of coconut oil with most of the fatty
acids removed and 40% by volume of anhydrous ethyl ether
and which was applied to the infected area once a day for
twenty days together with application of wet h2at by means
of hotl wet towels twice a day for twenty days. Subsequent
to this treatment, no recurrence of the "cold sore" lesions
was observed for a period of two years after treatment.
It will be appreciated that with the topical prepar-
14 ~2~7~ation of the present invention a safe means of delivering
ethyl ether to an epidermal area infected with Herpes
simplex virus is made possible. In this xespect~ the
anhydrous ethyl ether is emulsified in the refined and
bleached coconut oii carrier as described above so that
the heat instability of the anhydrous ethyl ether is
counteracted by the high boiling point of the coconut
oil carrier. In this way, the boiling point of the over-
all emulsion is raised from the normal boiling point of
ethyl ether at 34.6C (approximately 87~F) up to approx-
imately 54.4C (approximately 119F). This increase in
the bioling point of anhydrous ethyl ther in the emul-
sion enables the ethyl ether in the emulsion to be stored
more easily and more safely thereby to permit its use out-
side of the controlled environment of a hospital out-
patient clinic or a physician's office.
Also it will be appreciated that by utilizing ap-
plications of heat to the infected area in addition to the
application of the topical preparation healing of the
"cold sore" lesions is enhanced and expedited. As stated
above, it is believed this is caused by the increase in
blood flow to the infected area as a result of the heat
applied thereto.
Another important feature of the present invention
is that by using at least 30% by volume of anhydrous ethyl
ether in a refined and bleached coconut oil carrier, as op-
posed to an ether-linkage compound, a stronger agent is
used in the treatment of Herpes simplex virus thereby to
provide a more effective treatment. In this respect, the
anhydrous ethyl ether is more effective than the ether-
linkage compounds in destroying the viral envelope of
Herpes simplex virus thereby to prsvide a more effective
treatment. In this respect, the anhydrous ethyl ether
is more effective than the ether-linkage compounds in de-
35 stroying the viral envelope and the emulsion enables oneto apply a sufficient volume of ethyl ether to the infec-
ted area. Moreover, by using anhydrous ethyl ethex, vir-
tually no water is placed in contact with the infected
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area when the ether is applied thereby to aid further the
healing process.
Another advantage of the topical preparation of the
present invention is the use of refined and bleached coco-
nut oil which has much of the skin irritating tree ~attyacids removed therefrom. Moreover, the refined and
bleached coconut oil carrier serves to protect the infect
ted area during treatment thereof fro~l air and water which
are often deterents to the healing process.
From the foregoing description it will be apparent
that the method and topical preparation for treating
Herpes simplex virus of the present invention have a num-
ber of advantages some of which are described above and
others of which are inherent in the invention For exam-
ple, it has been observed that in treating a cold sore
vi.rus according to the teachings of the method of the pres-
ent invention and utilizing the topical preparation of the
present invention, local recurrence of cold sores is great-
ly minimized if not altogether eliminated, and such preven-
tion oE recurrence is greatly desired when treating Herpessimplex virus infectivity.
Moreover, from empirical tests it has been found
that the topical preparation applied according to the
methods of the present invention is effective in treating
in vivo Herpes I, Herpes II, "athlete's foot" fungus,
"jock itch" fungus and yeast infections and may be effec-
tive in treating Chicken Pox, Acne, Eczema, occlusions
and infections of pores tpimples and blackheads3, skin
rashes and canker sores.
