Note: Descriptions are shown in the official language in which they were submitted.
~i(3 3~7
T~EATMENT OF ACNE AND PERIORAL DERMATITIS AS
WELL AS FOR SKIN INFECTED WITH A HERPESVIRUS
Background
1. Field of the Invention
The present invention relates to a method and
composition for treating skin infected with a Herpesvirus,
and more particularly, to a method and composition for
treating skin infected with a Herpesvirus wherein an
ointment is topically applied tc the skin area infected.
10 It also relates to a method and composition for treating
acne and perioral dermatitis, and more particularly, to a
method and composition for treating acne and perioral
dermatitis wherein an ointmen~ is topically applied to the
skin area infected.
15 2 The Prior Art
Herpesviruses come in 70 different varieties, but
only a few are infectious to humans. The viruses
infections to humans include Herpesvirus hominis, which
causes herpes simplex; Herpesvirus varicellae, which
20 causes varicella (chicken pox) and zoster (shingles); the
Epstein-Barr virus, which causes mononucleosis; and
cytomegalovirus, which causes fetal infections.
Herpesviruses are also oEten responsible for fevers,
hepatitis, and pneumonia-like illnesses in children and
25 adults, especially those with lowered resistance. t
Additionally, eczema is caused by Herpesvirus
hominis or Poxvirus officinalis, and perhaps other viruses
such as Coxsackievirus.
A. H rpes Simplex
Of all the Herpesviruses, the effects of
Herpesvirus hominis are by far the most commonly
experienced. Herpesvirus hominis, which is responsible
for herpes simplex, has two different forms: Type I and
Type II. Type I causes ~erpes labialis (oral herpes) in
the form of cold sores and unsightly lesions around the
lips or nose. Type II causes H~rpes genitalis (genital
herpes) in the form of sores that appear below the waist,
primarily in the genital area. The two types vary little
with respect to -the nature of their behavior and either
one can take the other's place. Thus, Type II can cause a
cold sore while Type I can also infect the genitals.
Nevertheless, Type II is responsible for at least about
eighty percent (80~) of genital herpes.
Both Types I and II can be transmitted by sexual
as well as non-sexual contact; however, genital herpes is
generally transmitted through sexual intercourse. A Type
I infection of the genitals or a Type II infection of the
mouth can occur through oral-genital contact. A cold sore
virus may be transmitted when two persons kiss or by means
as simple as the use of the same towel to wipe their
faces. The eyes can be infected simply by rubbing them
after touching an infected area. Thus, there are a
variety of ways in which herpes simplex viruses I and II
can be transmitted. ~oreover, although not the usual
case, transmission of the viruses can even occur before
the symptoms of herpes simplex appear or before the
infected person is aware that he or she has herpes simplex.
The symptoms of herpes simplex infections include
the development of a cluster of tiny bumps or blisters,
sometimes preceded or accompanied by a fever or swollen
lymph glands. The blisters then crust over, and the sores
disappear -- usually within three weeks after the first
symptoms. However, the virus remains in the body for a
lifetime, hibernating in such places as the salivary
glands, the nerve tissue, and the lymph nodes. After
recovery from the first attack, subsequent infections may
occur over the next few years, until gradually the
frequency of attacks diminishes. Occasionally, however,
~ 26~33~7
-- 4 --
recurrences may appear over the rest of the individual's
life. The reappearance of herpes infections is then often
triggered by stress, fatigue, exposure to sun, trauma,
fever or menstruation.
Other complications may develop in those who are
afflicted with a herp~s simplex virus. If a person
suffering from herpes simplex touches a sore or blister
and then rubs his eyes, he may develop a serious eye
infection known as herpes keratitis. Thousands of
Americans annually lose their sight because of this
disease.
` For women, genital herpes simplex carries special
risks~ ~o begin with, genital herpes simplex has been
linked to cancer of the cervix. Female herpes victims are
five to seven times more likely to develop cervical cancer
than non-infected females. Genital herpes simplex can
also cause serious birth defects. A pregnant woman with
an active genital herpes simplex infection faces a fifty
percent (50~) chance of passinglthe disease to her baby as
the child passes through the birth canal. About fifty
percent (50%) of the newborn infants who develop herpes
simplex die of the infection; seventy-five percent (75~)
of those who survive suffer from blindness or brain
damage. Fortunately, if sores are found close to the time
of delivery, the doctor can perform a Caesarean-section to
prevent infection of the newborn as it passes through the
birth canal.
Most Americans have been exposed to the herpes
simplex virus; indeed, eighty percent (80%) of the
American population carries the herpes simplex virus, and
antibodies against the virus have been found in up to
ninety-five (95~) of blood samples tested. Although some
people never experience symptoms, (possibly because their
immune systems repulse the virus so it cannot sustain its
attack), about saven out of eight people who come in
~2~3397
sexual contact with the herpes simplex virus will contract
an infection. It is estimated that from thirty (30) to
seventy (70) million Americans suffer occasionally from
the most common form of herpes simplex infection, that of
coldsores. Moreover, it is estimated that from five (5)
to twenty (20) million Americans suffer from genital
herpes simplex, and that each year, half a million more
Americans join these ranks.
Since there has previously existed no known
effective treatment for herpes simplex, the total number
of persons inflicted with herpes simplex continues to
increase. Scientists have tried and rejected many
different treatments for herpes such as vitamin C, zinc,
ether and ice packs. It is evident that in the absence of
a treatment for herpes simplex, this relatively new
venereal disease could potentially reach epidemic
proportions.
B. Eczema
Another Herpesvirus disorder which plagues many
people is atopic eczema. Eczema occurs in primarily three
forms: (1) the infantile form, ~2) the adult form, and
(3) the localized form.
The infantile form of eczema may first appear
soon after birth, often by the fourth month of the
infant' 9 life. Infantile eczema is generally manifested
as processes which may be red, dry, slightly scaly,
cracked and excoriated, or sometimes moist and oozing.
Infantile eczema is most frequently manifested around the
face, scalp, neck and diaper areas. Older children and
young adults generally experience manifestation of the
disease in the flexural areas and the cheeks. In fewer
than half of the individuals inflected with infantile
eczema, the disease clears up by the age of four; yet even
in these individuals, the disease may occur at a later
age. The majority of eczema victims still experience
33~7
occasional flare ups through the young adult years, up
until about the age of thirty, at which time the disease
usually disappears.
The adult form of eczema is generally manifested
in the antecubital and popliteal areas, and in some cases
around the hands, feet and face. The infected skin is
generally dry, erythematous, and excoriated with bacterial
crusting and redness.
The localized form of eczema which occurs in
diverse individuals, is primarily manifested around the
wrists, ankles, hands, feet and ears, as well as the
perianal, perivulvar, and scrotal regions.
By far the worst consequence of atopic eczema is
the pruritis or itching which is associated with this
disease. ~hose inflicted with atopic eczema often find
pruritis to be a life-long companion. Any relief to be
had from such intolerable itching is gratifying to say the
least. There are many factors which play a role in the
occurrence of atopic eczema, such as dietetic and
emotional factors. Moreover, seasonal fluctuations are an
important factor with atopic eczema generally becoming
worse during the winter season.
One of the greatest fears of those who are
inflicted with antopic ec7ema, is that these individuals
are generally more susceptible to viral infection, and in
particular, to infestation by a herpes simplex virus or a
vaccinia virus. Additionally, those suffering from atopic
eczema are abnormally susceptible to environmental
irritants~ Consequently, those inflicted with the disease
are often advised to wear clothing which is soft and
light; to stay away from heat sources, to take brief baths
or showers not exceeding five minutes and using a minimal
amount of soap; to avoid primary irritants such as paints,
cleansers, solvents, chemical sprays, dusts, and the like;
and sometimes to change their residence to a warm, dry
-- 7 --
temperate, unvarying climate where temperature extremes
are ~arely experienced.
Although there is no known cure for atopic
eczema, there are various helpful treatments which all
have one goal in common: to stop the intolerable itching
that accompanies atopic ec7ema. Examples of these
treatments include antiseptics, for example antibacteral
cleansers such as Betadine (a registered trademark owned
by Purdue Frederick Co.; ~orwalk, Connecticut 06856) and
Hibitaine; topical glucocor-~icoids creams; systemic
glucocortroids; antipruritic agents; and antibiotics.
Although the atopic and systemic glucocorticoid treatments
have proven most effective in treating long-continued
atopic eczema, adverse topical and systemic effects are
often experienced when such treatments are used.
Consequently, adverse effects in those undergoing
glucocorticoid treatments must be carefully monitored.
It would, therefore, be extremely desirable to
provide an effective treatment for various disorders
caused by the Herpesviruses, especially herpes simplex.
Moreover, it would be desirable to provide an improved
treatment for Herpesvirus disorders such as eczema, which
is safe, having no known side effects in any body
locations. Such treatments are described and claimed
herein.
C. Acne
A common skin disorder which plagues nearly all
adolescents at some time or another is that of acne
vulgaris (commonly referred to as 'acne'). The peak
incidence of acne occurs at about fourteen (14) years of
age in girls and sixteen (16) years of age in boys, with
the most severe cases in boys tending to occur even
later. Although acne has generally been considered a
teenage problem, it is a disease for those who are in
their twenties and thirties as well. There are few
3~
diseases which produce more psychic trauma, maladjustment,
insecurity and feelings of inferiority than does acne.
The causes and factors influencing the
development of acne are many, and generally not well
understood. Acne is normally manifested in a variety of
lesions, including comedomes, papules, pustules, cysts,
and scars. These lesions occur in the skin areas having
the greatest concentration of sebaceous glands, e.g. the
face, central chest, and upper back. In severely affected
subjects, lesions may also appear on the arms, back of the
neck, lower back, buttocks and thighs.
In some adolescents, acne is manifested by other
more than a few scattered pustules and comedomes that have
a relatively short duration and produce no permanent
affects. Other adolescents, on the other hand, develop
more extensive acne that not only persists, but also
produces permanent pits and scars. The lesions which are
generally responsible for the scars are the tender, red
pustules and cysts. Some surveys indicate that over two
percent (2~) of all high school students have a severe
form of acne.
Many different treatments for acne have been
developed over the years; however, the effectiveness of
known treatments with respect to relatively difficult acne
problems has been rather limited. For mild cases of acne,
regular shampooing of the scalp and daily use of an
abrasive soap on the acne-infected skin are typical of
recommended treatments~
For treating moderate cases of acne, preparations
for drying and peeling the skin area subject to comedomes,
papules, and pustules are often recommended. Some typical
preparations for the treatment of moderate acne include a
powder-base shake lotion containing resorcinol and sulfur;
benzoyl peroxide; topical antibiotics such as erythromycin
and clindamycin; oral antibiotics such as tetracycline;
39'7
retinoic acid (vitamin A acid); as well as moderate
irradiation with ultraviolet light.
For treating more severe cases of acne where
pustular and cystic lesions cause scarring, a totally safe
treatment has previously not been found. Some
preparations which have been used to treat severe cases of
acne include those containing antibiotics,
glucocorticoids, or hormones. Many systemic antibiotics
carry undesirable or unwarranted side effects and risks,
thus restricting the use of antibiotics to those which are
mild and relatively safe, such as erythromycin and
tetracycline. Undesirable side effects and risks are also
experienced from the use of glucocorticoids and hormones.
For example, some side effects from estrogen-progesten
lS medications (a typical hormone treatment) include
thromboe~bolic disease, gallbladder disease, strokes,
myocardial infarcts, hepatic tumors, hypertension and
endometrial cancer. Moreover, the oral ingestion or
topical application of the female hormone estrogen by
males may result in other undesirable side effects, such
as the emergency of feminine characteristics.
Additionally, antiandrogens, ultraviolet light,
cryotherapy using solid carbon dioxide or liquid nitrogen,
minor surgery, chemosurgery, and even X-ray therapy have
been used in the treatment of severe cases of acne. As
with the other preparations or treatments, certain risks
or undesirable consequences are inherent in each of these
treatments as well. One important undesirable
characteristic of most all of the prior art acne
treatments is that the effects of these treatments are
often felt throughout the body, not just the localized
skin area requiring treatment.
D. Perioral Dermatitis
Another relatively common skin disorder is
perioral dermatitis. Perioral dermatitis, which primarily
3~1~
-- 10 --
plagues young adult women, is less common among men and
occurs occasionally in young children. This disorder is
usually manifested as a localized grouping of red papules,
vesicopapules, and papulopustules around the lips, mouth,
chin, paranasal area, and even the upper eyelids.
Periora~ dermatitis lesions often burn, and exacerbations
and remissions axe frequent. Moreover, the lesions
associated with perioral dermatitis generally worsen with
pregnancy and menstruation. Other factors which aggravate
perioral dermatitis lesions include heat and
perspirationO Generally, after three to six months from
onset, the lesions finally disappear.
Perioral dermatitis has proven to be resistant to
most therapy, although some treatments have been found to
be somewhat beneficial. Some of these treatments include
(1) tetracycline; (2) a 1% hydrocortisone preparation;
(3) the avoidance of all cosmetics, except for lipstick
and mascara, and (4) daily cleansing with soap. The
long-continued use of potent topical glucocorticoids has
been known to produce the adverse effects of perioral
dermatitis. Therefore, glucocorticoid treatments which
are used to treat perioral dermatitis lesions must be
limited in strength, or the disorder can be severely
complicated.
It would, therefore, be a significant advancement
in the field of dermatology to provide a more effective
treatment for acne, and especially for extremely severe
cases of acne, which is safe, having no known side effects
in any body locations. ~dditionally, it would be another
significant advancement to provide an effective treatment
for perioral dexmatitis, and especially a treatment which
would avoid the adverse effects of treatments such as
glucocorticoid treatments. Such treatments are described
and claimed herein.
3~7
-- 11 --
Brief Summary and Oblects of the Invention
The present invention relates to a treatment for
various types of disorders caused by Herpesviruses, and
most importantly, to a treatment for herpes simplex and
eczema. This novel combination herpes sim~lex and eczema
treatment comprises applying a preparation to the infected
skin area; the preparation comprising a carrier medicant
(such as hydrophilic ointment) to which is added a small
amount of triacontanol. This preparation may be
periodically applied to the infected skin area as needed.
The active ingredient in the preparation, triacontanol,
has proven to be safe and has no known side effects
anywhere in the body.
It is, therefore, an object of the present
lS invention to provide an effective treatment for disorders
caused by a Herpesvirus, and most especially, for herpes
simplex, eczema and shingles.
A further object of the present invention is to
provide a topical treatment for disorders caused by a
Herpesvirus in which only the infected skin area is
exposed to the medicant treatment.
The present invention also relates to an improved
acne treatment which is effective even for extremely
severe cases of acne. Moreover, the present invention
relates to an effective treatment for perioral
dermatitis. This novel combination acne and perioral
dermatitis treatment comprises applying a preparation to
the infected skin area; the preparation comprising a
carrier medicant (such as hydrophilic ointment~ to which
is added a small amount of triacontanol. This preparation
may be periodically applied to the infected skin area as
needed. The active ingredient ~n -the preparation,
triacontanol, has proven to be safe and has no known side
effects anywhere in the body.
~6~39~7
- 12 -
It is, therefore, an object of the present
invention to provide an improved acne treatment which i8
safe, and effective against even severe cases of acne.
Another object of the present invention is to
provide an effective treatment of perioral dermatitis.
A further object of the present invention is to
provide a topical treatment for acne and perioral
dermatitis in which only the infected skin area is exposed
to the medicant treatment.
These and other objects of the present invention
will become more fully apparent in view of the following
detailed description and appended claims.
Detailed Description of the Preferred Embodiment
The present invention relates to a method and
composition for treating skin infected with a
Herpesvirus. Each of the treatments for the various types
of Herpesvirus disorders (e.g., herpes simplex, eczema and
shingles~ is substantially the same, and includes the
topical application of a preparation comprising a carrier
medicant containing a small amount of triacontanol. The
triacontanol preparation may be applied periodically to an
infected skin area as needed. Indeed, clinical
experiments indicate that the preparation may be applied
several times daily without iden-tifiable side effects.
Consequently, the preparation may be applied whenever
needed to alleviate discomfort or to clear up lesions.
Shortly after application of thè preparation to a herpes
simplex lesion, the pain and itching as~ociated with
herpes simplex disappear. Repea~ed applica~ion causes the
herpes simplex lesion itself to disappear, often within a
few days.
The pxesent invention also relates to a method
and composition for treating acne and for treating
perioral dermatitis. Each of these treatments is
substantially the same, and includes the topical
- 13 -
application of a preparation comprising a carrier medicant
containing a small amount of triacontanol. The
triacontanol preparation may be applied periodically to an
infected skin area as needed. Indeed, clinical
experiments indicate that the preparation may be applied
several times daily without identifiable side effects.
Consequently, the preparation may be applied whenever
needed to alleviate discomfort or to clear up lesions.
The active ingredient in the preparation is
triacontanolO Triacontanol, also known as melissyl
alcohol, myricyl alcohol, or hydroxytriacontane, is a
straight-chain, aliphatic, thirty carbon waxy alcohol
having the formula CH3(CH2)28CH20H- Although
triacontanol has been found useful for such purposes as
fertilization of crops, to the inventor's knowledge,
triacontanol has not been used as the active ingredient in
any medical treatment~
Ex~erimental application of triacontanol to skin
infected with acne or a Herpesvirus shows that
triacontanol has the following advantageous qualities:
(1) it removes pain and itching; (2) it clears up lesions
associated with Herpesviruses such as herpes simplex
lesions; (3) it is anti-inflammatory; (4) it restores
lipid levels on the skin to normal levels (important with
respect to Herpesvirus disorders such as eczema); (5) it
is virus and bacteria static; and (6) it is safe and has
no known side effects in any body locations.
Experimental application of triacontanol to skin
infected with acne or perioral dermatitis shows that
triacontanol has the following advantageous qualities;
(1) it removes pain and itching; (2) it clears up acne
lesions and perioral dermatitis lesions; (3) it is
anti-inflammatory; (4) it restores lipid levels on the
skin to normal levels; (5) it is virus and bacteria
static; and (6) it is safe and has no known side effects
in any body locations.
03~7
- 14 -
The triacontanol preparation is prepared by
simply mixing a very small quantity of triacontanol, about
one hundredth of one percent (0.01~) by weight, with a
medicant base until thoroughly blended. Although 0.01%
triacontanol has been found sufficient for effective
treatment, quantities much smaller than this are also
likely to provide effective treatment.
An important consideration in the preparation is
the choice of an appropriate medicant base. The selected
medicant base must be compatible with the triacontanol so
as to maintain it in active form for effective
application. One ointment which has been employed in the
present triacontanol invention is a standard USP
hydrophilic ointment; a thousand grams of which contains5 the following compounds in the indicated amounts:
Hydrophilic Ointment - USP
Amount
Compound (grams)
Methylparaben 0.25
Propylparaben 0.15
Sodium lauryl sulfate 10
Propylene glycol 120
Stearyl alcohol 250
White petrolatum 250
Furified water 370
The ingredients of hydrophilic ointment USP,
which ointment is commonly available from a variety of
commercial sources, are combined as followsO First, the
stearyl alcohol and the white petrolatum are melton on a
steam bath and warmed to about 75C. The other
ingredients are dissolved in the purified water and are
also warmed to about 75C. All ingredients are then mixed
together and stirred until the mixture congeals.
It will be understood that the hydrophilic
ointment disclosed above is given by way of example only,
3~7
and that numerous other carrier medicants may also be
suitable, such as an oleic acid ointment base. Again, it
is the triacontanol, not the carrier medicant, which is
the active ingredient in the preparation, the carrier
medicant merely acting as a carrier for the -triacontanol
to provide for the effective application of the
triacontanol in active form to the skin. Thus, it will be
appreciated that one of the most important properties of
the carrier medicant is its ability to provide sufficient
contact between the active triacontanol and the skin to
effectively treat the skin.
The above-described triacontanol-hydrophilic
ointment preparation has been found to be effective in the
treatment of disorders caused by Herpesviruses, such as
herpes simplex, eczema, and zoster (shingles). In
particular, the preparation has especially been found to
be effective against herpes simplex and eczema. Moreover,
the above-described triacontanol-hydrophilic ointment
preparation has been found to be effective in the
treatment of acne and perioral dermatitis, which is
somewhat related to acne. Experimentally, the best
results have been obtained in using the preparation in the
treatment of perioral dermatitis.
Experimentally, the best results have been
obtained in using the preparation in the treatment of
herpes simplex (all types of lesions, particularly cold
sores) and eczema. Although the effect of the
triacontanol preparation on other Herpesvirus disorders
such as chicken pox, mononucleosis, fetal infections,
fevers, hepatitis, and pneumonia-like illnesses is yet
unknown, it is well-anticipated that the preparation may
also be effective in the treatment of these disorders.
Over twenty patients with herpes simplex lesions
in the form of cold sores have been treated with the
above-described triacontanol-bydrophilic ointment
39~
- 16 -
preparation. Upon topical application of the preparation,
these patien~s typically found that the itching associated
with the herpes simplex lesions disappeared after about 30
to 60 seconds and that the pain also disappeared after
about four to eight minutes. The effectiveness of the
preparation in aiding the healing process was found to
vary with the age o~ the lesion. Typically, it was found
that if a lesion was treated within ~our hours after its
initial appearance, the lesion disappeared completely
within only a few hours -- commonly within abou-t six
hours. For older lesions, it was found that treatment
caused the lesions to disappear in about one to seven
days, generally reducing the normal life of the lesion by
at least fifty percent (50%). Overall, the
triacontanol-hydrophilic ointment preparation decreased
the normal healing time for herpes simplex lesions by up
to eighty percent (80%) or more.
About 25 patients with atopic eczema were also
treated with the above-described triacontanol-hydrophilic
ointment preparation. The average patient treated had
experienced the symptoms of atopic eczema for at least ten
years and had suffered from the symptoms of atopic eczema
during at least forty percent (40%) of the previous year.
These patients found that their eczema lesions, which were
four weeks old on the average, were completely healed five
days after beginning treatment with the
triacontanol-hydrophilic ointment preparation. This is in
contrast to the three-week healing period which is
generally required when the well-known cortisone cream
treatments were used. Moreover, the severe itching
associated with the eczema lesions disappeared within two
hours after application of the triacontanol-hydrophilic
ointment preparation, whereas the cortisone creams
required about two weeks to dispell the itching.
Additionally, the pain and soreness associated with the
- 17 -
lesions commonly disappeared within only a few minutes
after application of the triacontanol-hydrophilic ointment
preparation, as opposed to about five days for the
cortisone creams. Finally, the triacontanol-hydrophilic
ointment preparation decreased ~he normal healing time for
the lesions dramatically.
Clinical studies were conducted on about fifteen
patients who, on the average, had experienced perioral
dermatitis over a period of at least three years, and had
experienced manifestations of the disorder at least twice
a year. Normally, three to six months were required to
heal the perioral dermatitis lesions of those patients.
After treatment with the triacontanol-hydrophilic ointment
preparation of the present invention, the time required
for healing was decreased dramatically. Moreover, the
itching associated with perioral dermatitis typically
disappeared within only a few seconds after application of
the triacontanol-hydrophilic ointment preparation to the
lesions.
One of the significant advantages of using
triacontanol as the active ingredient in the treatment of
the present invention is that triacontanol has proven
itself to be safe. Indeed, it occurs naturally in
alfalfa, honey and in the waxy portions of several edible
plants. Recently, it was found that triacontanol
dramatically increases crop yields when used as a
fertilizer. A group at Michigan State University
discovered that when as little as Eive milligrams of
triacontanol were mixed with 30 to 40 gallons of water in
the treatment of one acre of crops, growth was increased
by an average of 12 percent. Since triacontanol is a
common plant constituent, it is not unusual for one to
consume enough triacontanol in one meal to treat at least
an acre o~ crops.
- 18 -
Another indication that triacontanol is safe is
the fact that it is found naturally in beeswax as a
palmitate ester and possibly, in extremely small amounts,
as the simple alcohol itself. Beeswax has been used for
many years as a stiffening agent in many pharmaceutical
preparations such as cerates, ointments, pastes, and
petroxolins. Cerates are mostly used as dressings for
inflamed skin surfaces and contain sufficient beeswax to
give them a desired consistency. Moreover, many cosmetic
preparations such as all-purpose creams, night creams,
vanishing creams, lotions, mascaras, lipsticks, cream lip
rouge, and face and body makeup contain significant
amounts of beeswax. Thus, the long-time use of
beeswax-containing preparations may provide a basis for
the belief that triacontanol is safe when applied
topically.
Although found in many preparations presently on
the market, it is unclear why, if any triacontanol is
present in beeswax as the free alcohol, it is not active
against herpes simplex and other Herpesvirus disorders,
acne and perioral dermatitis. First of all, since it is
present in beeswax as the palmitate, it is thought that
triacontanol is to active when in the form of a palmitate
ester. Moreover, it is conjectured that even if a very
small amount of triacontanol is present as a free alcohol
in beeswax, perhaps the amount is too small to be
effective or perhaps the environment imposed by the other
constituents of beeswax in some way prohibits the
triacontanol from having any effect. This supposed
inhibitive effect could be due in part to hydrophobic
interaction between triacontanol molecules in ~he beeswax
environment. Additionally, the inactivity of any
triacontanol in beeswax might also possibly be explained
by the inability of the skin to effectively absorb any
triacontanol from the beeswax environment. Furthermore,
-- 19 --
it is also possible that very close contact between the
triacontanol and the monomolecular cell wall of the virus
is required for effective treatment. Such close contact
could very well be inhibited by the beeswax environment
surrounding any triacontanol which might be present.
Whatever the reason for the ineffectiveness of beeswax in
treating Herpesvirus disorders, acne and perioral
dermatitis, for purposes of the present invention, it will
be appreciated that the choice of an appropriate carrier
medicant for the triacontanol such as the hydrophilic
ointment described hereinabove, is very important.
It will be appreciated that the invention may be
embodied in other specific forms without departing from
its spirit or essential characteristics. The foregoing
descriptions are to be considered in all respects only as
illustrative and not restrictive. T~e scope of the
invention is, therefore, indicated by the appended claims
rather than by the foregoing description. All changes
which come within the meaning and range of equivalency of
the claims are to be embraced within their scope.
SUPPLEMENTA Y DISCLOSURE
AS originally disclosed, a triacontanol ointment
preparation is applied directly to the infected skin area
for treatment for disorders caused by Herpesviruses such
as herpes simplex, eczema and shingles, as well as for
acne and perioral dermatitis.
In an additional aspec , the invention relates to
a method for treating inflammatory skin disease and more
particularly to a novel method for treating human skin
infected with viral infections such as, for example,
Herpesvirus, but as well as to the treatment of other
infections of the skin where inflammation is a problem.
By inflammation is meant the destruction and
repair of the tissues in response to irritation, and the
means wher~by the irritant is removed.
- 20 -
Such a definition places no limits on the amount
of the response or the degree or kind of irritation.
Because irritation by the normal products of growing and
dying cells is related to the process of intercellular
communication that occurs physiologically, inflammation
merges with the normal behavior of tissues. When minimal
it may differ only in degree from the normal physiological
process by which tissues control their requirements from
their blood supply.
Inflammation is necessary for repair as well as
for -the removal of irritants. However, repair, as in
wound healing, differs only quantitatively from those
processes which control the normal growth and contour of
the tissues.
Swelling of the tissues is initially due to edema
fluid, but in more chronic inflammation white cell
infiltration may make a main contribution. The tissues
themselves often increase in size. Thus acanthosis and an
increase in the papillary vasculature is a usual response
of the epidermis and upper dermis to irritation. A
papular lesion following an insect bite may show a
considerable increase in the bulk of the tissue which may
persist after the initial edema has been resolved.
Pseudo-epithiliomatous hypertrophy is not unusual in
uncontrolled inflammation.
Heat is a usual consequence of increased flow of
blood through the skin. In acute lesions the skin may be
heated as a direct result of local increase in metabolic
rate. In chronic inflammation neither local metabolism
nor blood flow may be increased, and the skin may feel
cold~ Heat loss cannot be e~actly correlated with
redness, because, areas of fast flow may be on the border
of a more congested and slow-flowing system. Thus
conduction of heat to the surface of the skin may be
considerable over a large, deep arteriovenous fistula
3~7
- 21 -
while the upper dermis may show all the effects of severe
statis consequent on raised venous pressure.
The sensations that accompany inflammation of the
skin include burning, stinging, itching and tenderness,
and are thus more varied than in most internal organs.
Which of these sensations predominates depends in part on
the site, depth, intensity and duration of the
inflammatory process. Thus in uticaria stinging may
accompany transient superficial lesions, itching is the
usual sensation in papular uticaria or in lesions due to
histamine release, while pain and tenderness may accompany
deeper lesions of long duration, as in delayed pressure
uticaria.
Inflammation is a response to any irritation, and
the mechanism applies equally to infection, sunburn,
abrasions, contact dermatitis or the various patterns or
angiitis seen in dermatological practice. Studies of the
effects of injury -to the skin show early and delayed
phases of the inflammatory response, and these are similar
whether induced by trauma such as pressure or by
ultraviolet irradiation, or any of the factors listed.
It would be extremely desirable to provide an
effective treatment for inflammatory skin diseases.
This additional aspect of the invention is based
upon the discovery that triacontanol has been found to be
an effective agent for treating inflammatory skin diseases
infected with viral infections such as Herpesvirus or
other skin diseases such as dermatitis (eczema), contact
dermatitis, seborrheic dermatitis, atopic dermatitis,
scaling papular disease~ such as psoriasis and the like.
The invention will be described in greater detail in
con~unction with the treatment of Herpesvirus infections
such as herpes simplex infections and atopic eczema but as
will appear more fully hereinafter the present invention
is not limited to these skin diseases as other skin
diseases where inflammation is a problem have been
successfully treated with triacontanol.
The novel anti-inflammatory of the present
invention, triacontanol, is preferably used in association
with a pharmaceutically acceptable carrier, such as
hydrophilic ointment, designed to be applied topically to
human sXin infected with viral infections or other skin
diseases where inflammation is a problem.
Thus the present invention relates to a method
for treatiny inflammatory skin disease. Each of the
treatments for the various types of dermatitis is
substantially the same, and includes the topical
application of a preparation comprising a suitable
pharmaceutically acceptable carrier containing a small
amount of triacontanol.
The above-described triacontanol-hydrophilic
ointment preparation has been found to be effective in the
treatment of viral disorders such as dermatitis caused by
simplex, eczema, and zoster (shingles). The preparation
has also been found useful in the treatment of other skin
diseases such as seborrheic dermatitis, contact
dermatitis, atopic dermatitis and psoriasis. Moreover,
the triacontanol-hydrophilic ointment preparation has been
found to be effective against acne and perioral dermatitis.
Experimentally, the best results have been
obtained in using the preparation in the treatment of
herpes simplex (all types of lesions, particularly cold
sores) and eczema. Although the effect of the
triacontanol preparation on other Herpesvirus disorders
such as chicken pox, mononucleosis, fetal infections,
fevers, hepatitis, and pneumonia~like illnesses is yet
unknown, it is well~anticipated that the preparation may
also be effective in the treatment of these disorders.
Over thirty patients with herpes simplex lesions
in the form of cold sores have been treat~d with -the
~6~397
- 23 -
above described triacontanol-hydrophilic ointment
preparation. Upon topical application of the preparation,
these patients typically found that the itching associated
with the herpes simplex lesions disappeared after about 30
to 60 seconds and that the pain also disappeared after
about four to eight minutes. The effectiveness of the
preparation in aiding the healing process was found to
vary with the age of the lesion. Typically, it was found
that if a lesion was treated within four hours after its
initial appearance, the lesion disappeared completely
within only a few hours -- commonly within about six
hours. For older lesions, it was found that treatment
caused the lesions to disappear in about one to seven
days, generally reducing the normal life of the lesion by
at least fifty percent (50%). Overall, the
triacontanol-hydrophilic ointment preparation decreased
the normal healing time for herpes simplex lesions by up
to eighty percent (80%) or more.
Analysis of the data from thirty subjects
indicated that they had herpes simplex for variable
lengths of time from one to 45 years, with a mean of 12
years. In this group, herpes reoccurred one to 18 times
per year with a mean of six times per year.
Triacontanol significantly reduced healing time
in the 27 cases where healing time was indicated pre- and
post- treatment (pr. 0.0001). The mean healing time for
previous lesions was 10.9 days with a range from 3 to 21
days. The mean healing time after treatment with
triacontanol was 4.4 days with a range of 1 to 14 days.
Twenty-six out of twenty-eight (93~) subjects
indicated that triacontanol decreased healing time. When
further asked to quantify how much triacontanol decreased
healing time, the mean response was an ~0~ decrease.
Forty patients with atopic eczema were also
treated with the above-described triacontanol-hydrophilic
ointment preparation. The averge patient treated had
experienced the symptoms of atopic eczema for at least ten
years and had suffered from the symptoms of atopic eczem~
during at least forty percent (40%) of the previous year.
These patients found that their eczema lesions, which were
four weeks old on the average, were completely healed five
days after beginning treatment with the triacontanol
ointment preparation. This is in contrast to the three
week healing period which is generally required when the
well-known cortisone cream treatments were used.
As shown below treatment for various types of
disorders caused by skin inflammation and most
importantly, an anti-inflammatory treatment for the
following diseases as set forth in Tables 1-3 has been
15 successfully used.
Table 1
Viral disorders responsive to triacontanol Patients
Herpes Simplex 30
Shingles 5
- 25 -
Table 2
Disorders ~enerally responsive to triacontanol Patients
Seborrheic dermatitis 34
Eczema 40
Lichen Simplex Chronicus 8
Pruritus ani 3
Psoriasis 12
La-ter phase of contact dermatitis 12
Later phase of irritant dermatitis 20
10 Xerosis 22
Table 3
Disorders less responsive to triacontanol Patients
Lichen planus 2
Dermatitis herpetiformis
15 Lichen schlerosis et atrophicans
