GB1601796A

GB1601796A - Topical composition

Info

Publication number: GB1601796A
Application number: GB11779/78A
Authority: GB
Original assignee: Individual
Current assignee: Individual
Priority date: 1977-03-25
Filing date: 1978-03-23
Publication date: 1981-11-04
Also published as: FR2384497B1; FR2384497A1; JPS53133636A; CA1118354A; DE2812501A1

Description

(54) TOPICAL COMPOSITION (71) I, GEORGE FOLK SHERRIL. a citizen of the United States of America, residing at 405 - 39th Street, Newport Island, City of Newport Beach, State of California, United States of America, do hereby declare the invention, for which I pray that a patent may be granted to me, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention relates to a composition suitable for treating viral skin disorders and in particular relates to a composition for treating herpes zoster.

Herpes zoster, which is commonly known as shingles, is a viral disease which frequently causes excruciating, prolonged pain and discomfort. A typical shingles patient suffers a great amount of pain for a period of six weeks to six months. Further, other symptoms of the disease may continue for a year or longer and in some cases even for the rest of the patient's life. Blindness, neuritis. and partial paralysis are some of the severe disabilities which can result from the disease. One particularly bad characteristic of the ailment is that it tends to recur periodically. particularly in older patients.

To describe the disease in technical terms. the virus attacks one or more sensory ganglia, usually on one side of the body but sometimes on both. The inflammatory process can extend inward to the meninges and into the root entry zone of the spinal cord; occasionally it involves the ventral horns. resulting in lower motor neuron paralysis of more or less segmental distribution. The related peripheral nerve or nerves are involved by a true inflammatory neuritis. Encephalitis and myelitis occasionally occur in debilitated patients.

The earliest symptom is pain in the distribution of the affected root or roots around the trunk. or as a linear strip on the upper or lower limb, or in one or more divisions of the trigeminal nerve. It involves the pinna. external auditory meatus, and anterior pillar of the fauces in geniculate herpes. In rare instances the disease is painless. However, in most cases, the skin of the infected zone is hypersensitive even before the rash appears. In some cases muscular paralysis may appear within one or two weeks after the rash has appeared.

Such paralvsis is uncommon except in the case of geniculate herpes, which is usually accompanied by facial paralysis resembling Bell's palsy.

Postherpetic neuralgia is a common sequel, particularly in patients over fifty. The pain is persistent, and is usually aggravated by emotion and fatigue. Initially, the skin is sensitive to touch. but after a year or two this sensitivity disappears.

In ophthalmic herpes there is special danger to the eye, which may in some cases have a secondary bacterial infection. This secondary infection can lead to panophthalmitis.

Further. corneal opacities or glaucoma can also result from the herpes.

In most cases, herpes zoster occurs in otherwise healthy individuals. However, in a minority of cases, it occurs in a background of lymphoma, leukemia, carcinoma, radiation therapy. or the use of immunosuppressive drugs.

Prior methods of treatment of viral skin diseases such as shingles include the use of cortisone. steriods, anesthetics. etc. However, prior methods of treatment have been generally unsuccessful. Therefore. an effective method for the treatment of viral skin diseases is still desired.

The present invention provides a medicinal ointment suitable for topical application, especially for the treatment of viral skin diseases, comprising an amount of 0.01% to 10% by weight of captan and an amount from 0.01cue to 3% by weight of a surface active bactericide, said bactericide being a quaternary ammonium salt. together with an oleaginous ointment base.

In its preferred embodiment, the quaternary, ammonium salt comprises benzethonium chloride. The application of the composition to the infected areas, in many cases results in partial or complete remission of the disease.

The invention is more fully described hereinafter with reference to preferred embodiments.

The present invention provides an improved composition for the treatment of viral skin diseases such as shingles, herpes simplex I and II and warts. In its preferred embodiment, the composition comprises captan and benzethonium chloride. The composition is incorporated into a topical oleaginous vehicle to faciliate its application to the infected areas.

Captan is a known fungicide and bactericide and has the formula N (trichloromethylthio)-4-cyclohexene-1 ,2-dicarboximide. Suitable quaternary ammonium salts for the practice of the present invention include: cetyl pyridinium chloride, benzalkonium chloride, benzethonium chloride, methylbenzethonium chloride, thonzonium bromide, triclobisonium and domiphen bromide. However, it will be obvious to one skilled in the art that other types of surface active bactericides may also be utilized in combination with captan in the practice of the present invention.

The composition is incorporated into an oleaginous ointment base as a topical vehicle to facilitate its application to the infected areas. The topical vehicle functions to dilute the active ingredient and also functions to assist in the absorption of the active ingredients into the skin. Preferably, the vehicle is capable of dissolving substantial amounts of both the captan and the surface bactericide to form a topical preparation. Suitable vehicles are oleaginous ointment bases e.g. hydrophilic petrolatum, anhydrous lanolin, lanolin, hydrophilic ointment, cold cream, petrolatum, propylene glycol, polyoxyl stearate, glycol ethers and derivatives, cetyl and stearyl alcohol, stearic acid, mineral oils, castor oil, glycerin. polyethylene glycol, animal oil and vegatable oils such as olive oil, corn oil, peanut oil and cocoa butter. Other suitable vehicles include Brij 30 and Brij 35. "Brij" is a Registered Trade Mark for a series of polyoxyethylene ethers of fatty alcohols, e.g. cetyl, stearyl. oleyl or laurvl alcohols. Combinations of one or more of the above vehicles may also be utilized in the practice of the present invention. However, it will be obvious to one skilled in the art that other suitable topical vehicles may also be utilized in the practice of the present invention.

It will be obvious to one skilled in the art that the topical vehicle may also comprise, in addition to bodying agents, humectants. saponifying agents, emulsifiers. solvents penetrants, pH regulators, plasticizers, emollients, preservatives, hardening agents, pigments and perfumes.

In the practice of the present invention. it is preferred that the topical preparation further comprise a stabilizer to prevent decomposition of the active ingredients. Suitable stabilizers for the practice of the present invention are butylated hydroxytoluene (BHT) and tocopherol. However, it will be obvious to the art skilled that other suitable stabilizers may also be utilized in the practice of the present invention.

The topical preparation contains an effective amount of captan, i.e. from about 10% by weight to about 0.01% by weight, preferably about 1% by weight and an effective amount of the surface active bactericide, i.e. from about 3% to about 0.01% by weight, preferably about 0.1% by weight. The preparation further preferably contains an effective amount of stabilizer. e.g., from about 0.5% by weight to about 0.005% by weight, preferably about 0.02% by weight. In this regard, it should be noted that increasing the concentration of the captan and the surface active bactericide in the preparation can cause irritation of the skin and in some cases, allergic reactions. Thus, it is preferred that a minimum amount of both compounds which enables effective action and avoids allergic reaction be incorporated into the preparation. However. it will be obvious to one skilled in the art that for more recalcitrant conditions, it may be desired to increase the amount of the active ingredients in the preparation to enable effective action. Suitable topical preparation for the practice of the present invention are as follows: I. Captan --------------------------------- 1.00% III. Captan --------------------------------- 5.00% Benzethonium Chloride ----------- 0.10 Benzethonium Chloride ----------- 0.40 BHT ------------------------------------ 0.02 BHT ------------------------------------ 0.02 Brij 30 ---------------------------------- 10.00 Corn Oil ------------------------------- 30.00 Brij 35 ---------------------------------- 10.00 Petrolatum ---------------------------- 64.58 Cetyl Alcohol ------------------------ 10.00 100.00% Petrolatum ---------------------------- 68.88 100.00% II. Captan --------------------------------- 3.00% IV. Captan --------------------------------- 1.00% Benzethonium Chloride ----------- 0.03 Benzethonium Chloride ----------- 0.10 BHT ------------------------------------ 0.02 BHT ------------------------------------ 0.02 Caster Oil ------------------------------- 10.00 Brij 30 ---------------------------------- 7.50 Brij 35 ---------------------------------- 10.00 Brij 35 ---------------------------------- 7.50 Cetyl Alcohol ------------------------ 10.00 Cetyl Alcohol ------------------------ 7.50 Petrolatum ---------------------------- 66.95 Castor Oil ------------------------------- 7.50 100.00% Petrolatum ---------------------------- 68.88 100.00% All percentages by weight The topical composition is preferably spread thinly over the infected areas of the skin.

The composition is preferably applied to the infected areas once or twice a day until all of the symptoms disappear. In the treatment of shingles, upon the application of the agent to the infected areas, the pain is usually alleviated in a matter of seconds or minutes and the lesions and rashes begin to heal. With the palliation of pain, the patient can usually sleep comfortably, wear conventional clothes and lead a generally normal life. Eventually, the treatment results in remission of the lesions and rashes.

In the treatment of shingles and herpes simplex I and II the composition is most effective when it is applied during the early, active stages of the disease. Thus, in the treatment of shingles, the composition is preferably applied to the infected areas during the first six weeks following the onset of the symtoms of shingles. When the agent is applied more than six weeks, and more particularly, more than two months after onset of the symptoms of shingles, in some cases, the application of the agent does not result in palliation. It is believed that this is because the disease has by that time run its course and there only remains the aftereffects of the disease.

Although the rational for the successful results of the present method are not fully understood, it is believed that the captan and the surface active. bactericide cooperate synergistically to form a combination which enables an effective action against viral skin diseases. In the treatment of shingles, this effect is obtained even though neither ingredient is analgesic or anesthetic.

The composition of the present invention has been tested on several patients suffering from shingles. In each case a diagnosis of shingles was made by a medical doctor. In all cases a topical agent corresponding to that of Example I was applied topically to the infected areas of the skin. However, in some cases the preparation contained no stabilizer (BHT) and in those cases the percentage of petrolatum was 68.90. The topical preparation was prepared by combining the three alcohols (Brij 30, Brij 35 and cetyl) and the petrolatum in a vessel, and then gradually raising the temperature to about 125"F to melt the alcohols and the petrolatum. Purified captan, benzethonium chloride and BHT were then added to the melt with stirring and dissolved in the alcohols. The melt was then cooled with stirring to produce a homogeneous mass of ointment having the general appearance and consistency of petrolatum. The following are case histories of the treatment of these patients. It is to be understood that these histories are given by way of illustration and not of limitation.

Case History No. I A white female developed herpes zoster of the cervical plexus of her neck. Five days after the onset of the ailment. the topical preparation of the present invention was applied to the infected areas. On the day following application of the ointment the pain disappeared and the lesions began to dry out. Her only remaining symptom was a slight itching. All symptoms had disappeared within eleven days after onset of the disease.

Case History No. II A white female developed herpes zoster while hospitalized for treatment of bleeding gastric ulcers. The infected area was ocher right side. adjacent the 4-5 lumbar vertebrae.

The symptom of the disease was a small area of blisters which gradually extended toward the right. in a band about two inches wide and seven inches long. She experienced severe itching, burning and pain. Application of the topical preparation of the present invention gave immediate relief from pain and the eruption disappeared without about one week after application.

Case History No. III A white adult female developed severe pain during a particular day. and by that night the skin on her buttocks and the back of her thighs was very sore and there were spots on her left side. She was unable to sit down with comfort. The topical preparation of the present invention was applied to the infected areas and it substantially alleviated the pain. Three days later she returned to the doctor who had originally diagnosed the ailment as shingles and the doctor found her condition much improved.

Case History No. IV A white adult female had suffered from shingles over a period of several years and in some vears it had recurred several times during the year. No previous remedy had offered any relief. The topical preparation of the present invention was applied to the infected areas and the itching and the burning pain promptly diminished to the point where the patient felt comfortable. She maintained the areas "moist" with a preparation. which seemed to shorten the distress period. The disease has subsequently recurred periociically. but less frequently than prior to the first application of the preparation of the present invention.

Case History No. V A white adult female suffered from itching and knifing pains, and had a rash four to five inches wide on each side of her breasts. The case was diagnosed by a doctor as a well segmented case of shingles which would be expected to last about six weeks to six months.

The topical preparation of the present invention was applied two days after onset of the itching and pains and the first application relieved both itching and pains. With additional applications the rash completely disappeared in approximately two weeks after onset of the ailment.

Case History No. VI An adult male had red blotches on the neck and chest and itching and burning sensations.

Five days later, while still in discomfort, the patient applied the topical preparation of the present invention and achieved prompt relief. No discomfort recurred after application of the preparation.

Case History No. VII An adult female experienced a case of shingles which exhibited symptoms of extreme pain in the upper portion of the left side of her back and extended approximately half way around to her front at the waistline. After a few days of pain, the patient broke out around the waist with a painful rash similar to chicken pox eruptions. The topical preparation of the present invention was applied, and it gave immediate great relief. There was no extension of the rash in contrast with an earlier experience with shingles wherein the rash had extended to both sides of the patient.

Case History No. VIII An adult female who was suffering from shingles was unable to lay down in bed for five days due to the pain. Application of the topical preparation of the present invention to the infected areas achieved prompt relief from the pain. The patient was subsequently able to nightly enjoy several hours of sleep.

Case History No. IX An adult female who was suffering severe pain from shingles achieved relief within moments after the application of the topical preparation of the present invention. Although other preparations had previously been applied, none had alleviated the unbearable pain.

Case History No. X An adult female applied the topical preparation of the present invention to the infected regions after two weeks of suffering from shingles. Minutes after the application, the pain ceased and inflammation of the sores commenced to diminish.

Case History No. XI An adult female applied the topical preparation of the present invention to blisters of shingles which had formed on her face. Several applications were made to each blister which resulted in healing the blisters.

Case History No. XII An adult female suffered extreme discomfort, with related loss of sleep and nervous tension, caused by unrelieved symptoms. Other ointments had been used without success.

The topical preparation of the present invention was applied about three months after onset of the disease and it provided immediate relief. Thereafter, for a period of about a year and a half, the residual symptoms were kept under control by repeated applications of the preparation.

Case History No. XIII An adult female suffering from shingles exhibited symptoms of swelling in one eye, so that the eye was almost swollen shut. The topical preparation of the present invention was applied to the eye-lid and surrounding area. Immediately, all progress of the disease was arrested and eventually with repeated application remission of the disease occurred.

Case History No. XIV An adult female with facial herpes zoster applied the topical preparation of the present invention after scabs had formed. The preparation softened the scabs and relieved all sensitivity in the area.

Claims

WHAT I CLAIM IS:

1. A medicinal ointment suitable for topical application comprising an amount of 0.01% to 10% by weight of captan and an amount from 0.01% to 3% by weight of a surface active bactericide, said bactericide being a quaternary ammonium salt, together with an oleaginous ointment base.

2. The composition of claim 1 wherein the base contains petrolatum.

3. The composition of claim 1 or 2 wherein the base is selected to include hydrophilic petrolatum, anhydrous lanolin, lanolin. hydrophilic ointment, cold cream, propylene glycol, polyoxyl stearate, glycol ethers and derivatives, cetyl and stearyl alcohol, stearic acid, mineral oils, castor oil, glycerin, polyethylene glycol, animal oil, olive oil, corn oil, peanut oil or cocoa butter.

4. The composition of any one of claims 1 to 3 wherein said quaternary ammonium salt is selected from benzalkonium chloride, methylbenzethonium chloride. triclobisonium and domiphen bromide.

5. The composition of any one of claims 1 to 3 wherein said quaternary ammonium salt is benzethonium chloride.

6. The composition of any of the preceding claims which further comprises a stabilizer.

7. The composition of claim 6 wherein said stabilizer is butylated hydroxytoluene or tocopherol.

8. The composition of claim 6 or 7 which comprises from 0.005% to 0.5% by weight of said stabilizer.

9. The composition of claim 1 comprising about 1.0% by weight captan, about 0.1% by weight benzethonium chloride, about 0.02% by weight butylated hydroxytoluene, and about 98.88% by weight of the oleaginous ointment base.

10. The composition of claim 1, substantially as illustrated by preparation I herein.

11. The composition of claim 1, substantially as illustrated by preparation II herein.

12. The composition of claim 1, substantially as illustrated by preparation III herein.

13. The composition of claim 1, substantially as illustrated by preparation of IV herein.