Treatment of herpes simplex infections and acne

There is disclosed a method of treating inflammatory viral infections, acne and dermatitis conditions comprising the administration of an effective dosage of 3,3-Bis(p-hydroxyphenyl)phthalide (phenolphthalein). The dosage may be administered orally or topically depending on the condition being treated.

BACKGROUND OF THE INVENTION 
This invention relates to the discovery that 3,3-Bis 
(p-hydroxyphenyl)phthalide is an effective treatment for certain 
inflammatory skin conditions, especially those of a viral origin. 
Phenolphthalein has long been known as one of a group of primary 
diphenylmethane cathartics. The cathartic effect of phenolphthalein was 
reportedly discovered in 1902 and since that time it has been widely 
employed in laxative formulas. It is also reported that phenolphthalein is 
relatively nontoxic. Goodman & Gillman, Pharmacological Basis of 
Theraputics (4 Ed. 1977) "Cathartics and Laxatives" pp. 1021 and 1022. 
Phenolphthalein is also used as an indicator in titrations of mineral and 
organic acids and most alkalies. 
Although inflammatory viral infections may be caused by a wide variety of 
viruses, a common virus which produces persistently hard to treat 
conditions is the Herpes Simplex virus. Type I normally produces above 
waist infections while Type II produces lesions below the waist, in the 
genital region. Common manifestations of Herpes Simplex I infections are 
labialis (cold sores, fever blisters, etc.) pharyngitis, keratitis, skin 
infections (herpetic whitlow), encephalitis, and chronic ulcerative 
stomatitis. Herpes Simplex Type II may cause progenitalis oropharyngeal 
infections, meningitis and encephalitis. Other manifestations of 
inflammatory viral infections are canker sores, sun blisters and other 
such skin lesions and ulcerous conditions. 
Inflammatory viral infections have proven very difficult to treat and in 
many instances are allowed to run their course with symptomatic treatment 
such as ointments, local anesthetics and the like. Treatment for Herpes 
Simplex infections includes dusting with bismuth formic iodide, 
application of camphor spirit, ephinephrine, idoxuridine, adenine 
arabinoside, large doses of steroids and X-ray or grenz ray therapy. 
Inflammatory skin conditions (dermatitis) which occur frequently include 
photodermatitis and actinic dermatitis such as sunburn, actinic karatosis 
and the like, eczema, pruritus, acute and chronic lesions, burning, 
swelling and blistering. These conditions are also difficult to treat with 
moisturizing creams, lotions and other topical agents being employed. 
Acne is a disease of the pilosebaceous unit which includes the hair 
follicle and its sebaceous gland. They are most numerous on the face but 
also are found in abundance on the back, chest and upper arms. (L. 
Kaminester, "Acne," Journal of the American Medical Association, May 19, 
1978, Volume 239, No. 20, pages 2171-72) Normally the sebaceous glands 
secrete an oily material called sebum which rises to the top of the hair 
follicle and then flows out onto the skin surface. Acne occurs when the 
canals through which the oily sebum flows become plugged up. Bacteria, 
chiefly Corynebacterium acnes, live in the hair follicles and break down 
complex fats into triglycerides and free fatty acids. 
The plugged hair follicles, or comedo, often ruptures into the lower skin 
areas and dumps free fatty acids, horn, fat, hair and bacterial products 
into the dermis, creating a "toxic" foreign body response which can cause 
scarring. Recently recommended treatment of acne includes oral antibiotics 
that effectively decrease the bacterial count of C acnes. These include 
tetracycline and erythromycin which selectively concentrate around the 
hair follicles, thus reducing the C acnes count and subsequent 
inflammation. Those antibiotics may also be applied in topical 
application. Kaminester reports that topical applications of antibiotics 
are inferior to orally administered antibiotics and should not be used in 
severe cases of inflammatory acne. Topical tretinoin and benzoyl peroxide 
preparations have also had beneficial effects. 
It is an object of the present invention to provide a fast acting, 
effective treatment of inflammatory viral infections. 
It is a further object to provide a topical agent to arrest dermatitis 
conditions. 
It is yet a further object of the invention to provide a topical agent 
which reducts the C acne count in hair follicles and thereby helps prevent 
and aids in curing acne. 
SUMMARY OF THE INVENTION 
The method of the invention provides for the treatment of inflammatory 
viral infections by the administration of an effective oral or topical 
dosage of phenolphthalein. The orally administered dose is preferably 
about 15 to about 30 milligrams of phenolphthalein administered every 8 
hours to treat inflammatory viral infections including Herpes Simplex I 
and II infections, canker sores, cold sores and sun blisters. Although 
higher dosages, for example up to about 100 milligrams, of the oral 
preparation are effective against inflammatory viral infections, the 
preferred dosages are selected to avoid the laxative effect of the 
phenolphthalein. The phenolphthalein may advantageously be formulated with 
other drugs to provide relief from symptoms associated with the disease 
being treated. 
Phenolphthalein may also be applied as a topical agent within the scope of 
the invention to relieve or cure Herpes Labialis, cold sores, sun 
blisters, canker sores, photodermatitis, actinic dermatitis, actinic 
keratosis and dermatitis manifested as pruritus, acute and chronic 
lesions, burning, swelling, and blistering. When applied as a topical 
agent phenolphthalein is mixed with a suitable carrier and may be 
formulated to provide a moisturizing cream with anti-viral action. 
In a topical preparation including antibiotics, phenolphthalein may be 
applied to effectively treat acne. In such applications the suitable 
carrier will be selected to avoid comedogenic agents.

DETAILED DESCRIPTION 
In an informal clinical study 41 patients with symptoms of Herpes Labialis 
were treated with oral dosages of phenolphthalein. The patients were 
treated at different times over a period of about two months. The initial 
dosage was one hundred milligrams administered every 8 hours for the first 
day and every 12 hours thereafter. Due to complaints related to the 
laxative effect of the phenolphthalein, the dosage was reduced to 30 
milligrams in the early stages of the testing. Of the 41 patients treated, 
39 made complete recovery within two days without any noticeable 
development of the cold sore. The other two patients made complete 
recovery with no swelling or visible evidence of the cold sore remaining 
after three days. A control group of 24 patients with Herpes Labialis 
history were selected at random from clinical files as a control group. Of 
the 24 patients, 5 were excluded because of the total absence of early 
indications of infection. The other 19 patients were treated 
conventionally over a 10 day period. Only 4 experienced even partial 
relief from developing cold sores and 15 developed active cold sores and 
blisters which lasted up to 4 weeks. 
Follow-up observations on the 41 patients treated with phenolphthalein 
disclosed no development of Herpes Labialis. The results of this informal 
study indicate that phenolphthalein is a very effective drug for 
preventing and arresting the development of cold sores and blisters at the 
time of initial appearance in patients. 
Oral dosages of phenolphthalein have been successfully administered to 
victims of Herpes Simplex infections, including cold sores, fever blisters 
and Herpes Genitalis. Oral dosages have also proved effective to relieve 
and cure canker sores within a matter of hours. 
Phenolphthalein has successfully been combined with agents to relieve other 
cold and flu symptoms often associated with inflammatory viral infections. 
Tablets were prepared for this purpose having the ingredients listed in 
Table 1. In some formulations the phenolphthalein content was one hundred 
milligrams but this amount was reduced to thirt milligrams because of 
complaints of the laxative effect. Other formulations comprising 
antihistamines, decongestants, analgesics and antipyretics will be readily 
apparent to those skilled in the art and may be selected for specific 
conditions to be treated. 
TABLE I 
______________________________________ 
Nominal Analyzed 
Ingredient Amount Amount 
______________________________________ 
Phenolphthalein 30 mg. 27.6 mg. 
Acetaminophen 325 mg. 316. mg. 
Caffeine 33 mg. 36.1 mg. 
Chlorpheniramine Maleate 
2 mg. 1.9 mg. 
Phenylephrine HCI 10 mg. 9.7 mg. 
______________________________________ 
The inventor has been contacted by more than 20 men and women who indicated 
they were Herpes Simplex sufferers and that they received relief from cold 
sores and other Herpes Simplex inflammations by taking the tablets. The 
recommended dosage is one tablet every eight hours for the first day 
followed by one tablet every twelve hours until symptoms disappear. One 
person reported that she was a cold sore sufferer for years and that her 
ingestion of tablets, having either 30 or 100 milligrams of 
phenolphthalein with the remainder of the ingredients as set forth in 
Table 1, provided satisfactory results in combating cold sores. 
A male who used tablets having the composition set forth in Table 1 
reported that he had suffered from diagnosed Herpes Simplex II since 1972. 
He reported he took the recommended dosages and that the development of 
Herpes Simplex II was haulted. 
Phenolphthalein has also been prepared for topical application by 
formulating it at a concentration of 250 mg. per ounce with Natural 
Callagen Protein with pro-vitamin D-panthenol, lecithin and allantoin. The 
topical formulation provided a moisturizing cream which was effective in 
treating dermatitis conditions including photodermatitis, actinic 
dermatitis, actinic karatosis, eczema, pruritus, acute and chronic 
lesions, burning, swelling, blistering and acne. 
Phenolphthalein was formulated at the same concentration in a topical 
ointment with benzoyl peroxide and calamine base and demonstrated to be 
effective in providing relief from acne vulgaris and acne conglobate. 
In treating dermatitis conditions one formulation included 500 milligrams 
of phenolphthalein combined with 2 ounces of a moisturizing skin cream 
containing purified water (USP), Vitamin E, polyoxyethylene monostearate, 
glyceraol monostearate, propylene glycol, cetyl alcohol, stearyl alcohol 
and parabens. That topical preparation was effective in promoting quick 
healing and growth of new skin in the treatment of rashes, blemishes and 
skin lesions commonly associated with old age. 
As will be readily appreciated by those skilled in the art, phenolphthalein 
for oral application may be formulated with a variety of other agents to 
treat disease conditions associated with the disease for which 
phenolphthalein is selected. While orally administered phenolphthalein is 
effective in dosages at least up to 100 milligrams, the preferred dosage 
is from about 15-30 milligrams in order to avoid the objectionable 
laxative effect. The oral dosage may be administered in tablet, suspension 
or solution form. 
In preparing topical applications for the treatment of dermatitis 
conditions or acne it is within the scope of the invention to formulate 
phenolphthalein with suitable carriers to aid in the application on and 
absorption into the effected area. Such carriers are well known to those 
skilled in the art. In topical applications the concentration of the 
phenolphthalein in the carrier may vary widely. For example 500 mg. in 2 
ounces of carrier is effective against acne. It is believed that a 
concentration of at least about 250 mg. per ounce of carrier will be 
effective. However, the scope of the invention includes all effective 
concentrations. 
While specific formulations have been given above it is not intended that 
they limit the scope of the invention. The invention is limited only by 
the scope of the appended claims set forth below.