CA1260397B - Treatment of acne and perioral dermatitis as well as for skin infected with a herpesvirus - Google Patents

Abstract

ABSTRACT
A treatment for inflammatory disorders such as herpes simplex, exzema, shingles, atopic dermatitis, psoriasis, Seborrheic dermatitis, Lichen Simplex Chronicus, Pruritus ani, later phase of contact dermatiti later phase of irritant dermatitis, Xerosis, Lichen planus, Dermatitis herpetiformis and lichen sclerosis et atrophicans. The treatment include the topical application of an ointment base containing a small quantity of triacontanol. The triacontanol-ointment preparation is applied directly to the infected skin area as often as is needed.

Description

~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 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 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~

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 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 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 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 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 contains 5 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~

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 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.

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, 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.

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 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 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 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

Claims (31)

1. A chemical composition for the treatment of inflammatory skin disease which comprises a hydrophilic ointment and from about 0.01% to about 1% by weight of triacontanol, said triacontanol being present in an effective amount for the treatment of inflammatory skin diseases.

2. A composition for treating skin infected with acne, perioral dermatitis, or Herpesvirus, which comprises an effective amount of from about 0.01 to about 1% by weight of triacontanol together with a pharmaceutically acceptable carrier medicant.

3. A composition as defined in claim 2 wherein the carrier medicant is a hydrophilic ointment.

4. A composition as defined in claim 1 or 2 wherein the percentage of triacontanol blended with the carrier medicant is about 0.01% by weight.

5. A chemical composition as in claim 1 or 2 for treating acne. perioral dermatitis, or Herpesvirus, comprising:
a hydrophilic ointment; and triacontanol, said triacontanol being dispersed throughout the hydrophilic ointment.

6. A chemical composition as in claim 1 or 2 for treating herpes simplex, comprising:
a hydrophilic ointment; and triacontanol, said triacontanol being dispersed throughout the hydrophilic ointment.

7. A chemical composition as in claim 1 or 2 for treating acne and perioral dermatitis comprising:
a hydrophilic ointment; and triacontanol, said triacontanol being dispersed throughout the hydrophilic ointment.

8. A chemical composition as in claim 1 or 2 for treating eczema and shingles comprising:
a hydrophilic ointment; and triacontanol, said triacontanol being dispersed throughout the hydrophilic ointment.

9. A chemical composition for the treatment of inflammatory skin disease which comprises an effective amount of triacontanol together with a pharmaceutically acceptable carrier.

10. A composition for treating skin infected with herpes simplex which comprises an effective amount of triacontanol together with a pharmaceutically acceptable carrier.

11. A composition for treating skin infected with an eczema virus which comprises an effective amount of triacontanol together with a pharmaceutically acceptable carrier.

12. A composition for treating skin infected with a zoster virus which comprises an effective amount of triacontanol together with a pharmaceutically acceptable carrier.

13. A composition as defined in claim 10, 11 or 12 wherein the carrier is a hydrophilic ointment.

14. A composition as defined in claim 10, 11 or 12 wherein the carrier is an oleic acid based carrier.

15. A composition as defined in claim 9 wherein the carrier is in the form of an ointment.

16. A composition for the treatment of seborrheic dermatitis which comprises an effective amount of triacontanol together with a pharmaceutically acceptable carrier.

17. A composition as defined in claim 16 in which the carrier is a hydrophilic ointment.

18. A composition as defined in claim 16 in which the carrier is an oleic acid-based carrier.

19. A composition as defined in claim 18 in which the carrier is in the form of an ointment.

20. A composition for the treatment of psoriasis which comprises an effective amount of triacontanol together with a pharmaceutically acceptable carrier.

21. A composition as defined in claim 20 in which the carrier is a hydrophilic ointment.

22. A composition as defined in claim 20 in which the carrier is an oleic acid-based carrier.

23. A composition as defined in claim 22 in which the carrier is in the form of an ointment.

24. A composition for the treatment of acne which comprises an effective amount of triacontanol together with a pharmaceutically acceptable carrier.

25. A composition as defined in claim 24 in which the carrier is a hydrophilic ointment.

26. A composition as defined in claim 24 in which the carrier is an oleic acid-based carrier.

27. A composition as defined in claim 26 in which the carrier is in the form of an ointment.

28. The use of triacontanol for treating of inflammatory skin disease.

29. The use of triacontanol for treating skin infected with herpes simplex.

30. The use of triacontanol for treating skin infected with an eczema virus.

31. The use of triacontanol for treating skin infected with a zoster virus.
SD32. A chemical composition as in claim 1 or 9 wherein the inflammatory skin disease is one oE Seborrheic dermatitis, Lichen Simplex Chronicus, Pruritus ani, Psoriasis, later phase of contact dermatitis, later phase of irritant dermatitis, Xerosis, Lichen planus, Dermatitis herpetiformis and lichen sclerosis et atrophicans comprising;
a hydrophilic ointment; and triacontanol, said triacontanol being dispersed throughout the hydrophilic ointment.