U.S. patent application number 09/976915 was filed with the patent office on 2002-03-21 for method of treating dermatoses using avermectin compound.
Invention is credited to Parks, L. Dean.
Application Number | 20020035076 09/976915 |
Document ID | / |
Family ID | 25524622 |
Filed Date | 2002-03-21 |
United States Patent
Application |
20020035076 |
Kind Code |
A1 |
Parks, L. Dean |
March 21, 2002 |
Method of treating dermatoses using avermectin compound
Abstract
A method for treating dermatoses including transient
acantholytic dermatitis, acne miliaris necrotica, acne
varioliformis, perioral dermatitis, and acneiform eruptions is
disclosed. The method includes topical application of a
dermatological composition containing an avermectin compound to the
affected areas of a patient.
Inventors: |
Parks, L. Dean; (Ocala,
FL) |
Correspondence
Address: |
MELVIN K. SILVERMAN
4901 NORTH FEDERAL HIGHWAY
FORT LAUDERDALE
FL
33308
US
|
Family ID: |
25524622 |
Appl. No.: |
09/976915 |
Filed: |
October 12, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09976915 |
Oct 12, 2001 |
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09605747 |
Jun 29, 2000 |
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6319945 |
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Current U.S.
Class: |
514/28 ;
424/447 |
Current CPC
Class: |
Y10S 514/859 20130101;
A61K 31/704 20130101; A61P 17/00 20180101; A61Q 19/00 20130101;
A61K 31/35 20130101; A61K 8/498 20130101; A61P 17/10 20180101 |
Class at
Publication: |
514/28 ;
424/447 |
International
Class: |
A61K 031/7048; A61L
015/16 |
Claims
What is claimed is:
1. A method of treating a dermatosis comprising topically applying
a therapeutically effective amount of an avermectin compound to an
affected area of a patient, wherein said dermatosis is one disease
selected from the group consisting of transient acantholytic
dermatitis, acne miliaris necrotica, acne varioliformis, perioral
dermatitis, and acneiform eruptions.
2. The method of claim 1, wherein said avermectin compound is in a
dermatological composition comprising an effective amount of said
avermectin compound and a pharmaceutically acceptable carrier.
3. The method of claim 2, wherein said pharmaceutically acceptable
carrier comprises water, glycols, alcohols, lotions, creams, gels,
emulsions, sprays, shampoos, soaps, body washes, facial cleansers,
and facial masks.
4. The method of claim 3, wherein said dermatological composition
is integrated in medicated tape, topical dressing, dermal patch, or
cleansing tissue.
5. The method of claim 4, wherein said avermectin compound
comprises avermectins, avermectin derivatives, ivermectin, or
ivermectin derivatives.
6. The method of claim 5, wherein said avermectin compound in said
dermatological composition is in a concentration greater than about
0.05% (w/v).
7. The method of claim 5, wherein said avermectin compound in said
dermatological composition is in a concentration range from about
0.05% to about 8% (w/v).
8. A method of treating a dermatosis comprising the steps of: (a)
topically applying an initial dosage of a therapeutically effective
amount of an avermectin compound to an affected area of a patient
for an initial treatment period, and (b) thereafter topically
applying a maintenance dosage of an avermectin compound to said
affected areas for maintenance; wherein said dermatosis is one
disease selected from the group consisting of transient
acantholytic dermatitis, acne miliaris necrotica, acne
varioliformis, perioral dermatitis, and acneiform eruptions.
9. The method of claim 8, wherein said initial treatment period is
from about one week to several weeks.
10. The method of claim 8, wherein said avermectin compound
comprises avermectins, avermectin derivatives, ivermectin, or
ivermectin derivatives.
11. A method of treating a dermatosis comprising topically applying
a therapeutically effective amount of ivermectin to an affected
area of a patient, wherein said dermatosis is one disease selected
from the group consisting of transient acantholytic dermatitis,
acne miliaris necrotica, acne varioliformis, perioral dermatitis,
and acneiform eruptions.
12. The method of claim 11, wherein said ivermectin is in a
dermatological composition comprising an effective amount of said
ivermectin and a pharmaceutically acceptable carrier.
13. The method of claim 12, wherein said pharmaceutically
acceptable carrier comprises water, glycols, alcohols, lotions,
creams, gels, emulsions, sprays, shampoos, soaps, body washes,
facial cleansers, and facial masks.
14. The method of claim 13, wherein said dermatological composition
is integrated in medicated tape, topical dressing, dermal patch, or
cleansing tissue.
15. The method of claim 12, wherein said ivermectin in said
dermatological composition is in a concentration greater than about
0.05% (w/v).
16. The method of claim 12, wherein said ivermectin in said
dermatological composition is in a concentration range from about
0.05% to about 8% (w/v).
17. A method of treating a dermatosis comprising the steps of: (a)
topically applying an initial dosage of a therapeutically effective
amount of ivermectin to an affected area of a patient for an
initial treatment period, and (b) thereafter topically applying a
maintenance dosage of ivermectin to said affected area for
maintenance; wherein said dermatosis is one disease selected from
the group consisting of transient acantholytic dermatitis, acne
miliaris necrotica, acne varioliformis, perioral dermatitis, and
acneiform eruptions.
18. The method of claim 17, wherein said initial treatment period
is from about one week to several weeks.
19. A kit for treating transient acantholytic dermatitis, acne
miliaris necrotica, acne varioliformis, perioral dermatitis, or
acneiform eruptions comprising: (a) a dermatological composition in
a container, said dermatological composition comprising an
avermectin compound and a pharmaceutically acceptable carrier, and
(b) a set of instructions on or associated with said container on
how to use said dermatological composition for treating transient
acantholytic dermatitis, acne miliaris necrotica, acne
varioliformis, perioral dermatitis, or acneiform eruptions.
20. The kit of claim 19, wherein said avermectin compound comprises
avermectins, avermectin derivatives, ivermectin, or ivermectin
derivatives.
21. The kit of claim 20, wherein said avermectin compound is
ivermectin.
22. The kit of claim 21, wherein said ivermectin in said
dermatological composition is in a concentration range from about
0.05% to about 8% (w/v).
23. The kit of claim 19, wherein said pharmaceutically acceptable
carrier comprises water, glycols, alcohols, lotions, creams, gels,
emulsions, sprays, shampoos, soaps, body washes, facial cleansers,
and facial masks.
24. The kit of claim 19, said dermatological composition is
integrated in medicated tape, topical dressing, dermal patch, or
cleansing tissue.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of co-pending
patent application Ser. No. 09/605,747 filed Jun. 29, 2000, which
is herein incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to methods for treating
various dermatoses including transient acantholytic dermatitis,
acne miliaris necrotica, acne varioliformis, perioral dermatitis,
and acneiform eruptions.
BACKGROUND OF THE INVENTION
[0003] Transient acantholytic dermatitis, acne miliaris necrotica,
acne varioliformis, perioral dermatitis, and acneiform eruptions
are common dermatological diseases. Each of the dermatoses has its
own etiology and histology.
[0004] 1. Transient acantholytic dermatosis
[0005] Transient acantholytic dermatosis, also called syn Grover's
disease, is an acquired skin disease which is seen as itchy papules
and vesicles resulting in soreness over the area. The lesions
appear on the shoulders, neck, thighs, scalp rapidly. Some of the
papules can become rough and may have crusting. The disease mostly
occurs in meddle to old age, especially in men. Unlike the name of
the disease, the condition is not transient, and can last for
years.
[0006] The cause of the disease is unknown, however, various
factors are thought to precipitate the disease, including sun
exposure and sun burn, heat exposure, sweating, fever, radiation
treatment, and cancers. There is no specific treatment for this
disease. Currently, topical steroids, systemic steroids, oral
vitamin A, etretinate, PUVA (psoralen and long-wave ultraviolet
radiation) and Accutane.RTM. (isotretinoin, manufactured by Roche)
have been used clinically.
[0007] 2. Acne miliaris necrotica and acne varioliformis
[0008] Acne miliaris necrotica, also called scalp folliculitis,
consists of follicular vesicopustules, frequently solitary, usually
very itchy and tender, which appear anywhere in the scalp or
adjacent areas. It can range from an occasional nuisance that many
people experience to a chronic problem that can be quite
troublesome. The severe form of the disease which leaves large
scars is called acne varioliformis. The condition is more common in
people who are doing activities that make them sweat or who wear
occlusive head gear. Stress often seems to trigger outbreaks as
well. Existing treatments range from antibiotic shampoos such as
Capitrol.RTM. (a chloroxine shampoo), astringent compresses,
topical antibiotics or steroids to oral antibiotics. In extreme
cases, Accutane.RTM. has been used, which is well known for the
severe adverse side effects that can cause.
[0009] 3. Perioral dermatitis
[0010] Perioral dermatitis is a chronic papulopustular facial
dermatitis. It mostly occurs in younger women. The incidence is
estimated as 0.5-1% in industrialized countries, independent of
geographical factors. The disease is limited to the skin. Skin
lesions occur as grouped follicular reddish papules, papulovesicles
and papulopustules on erythematous base with a possible confluent
aspect. In an extreme variant of the disease, called lupuslike
perioral dermatitis, granulomatous infiltrates occur with a
yellowish aspect in diascopy. Although perioral dermatitis is
limited to the skin and not life threatening, emotional problems
may occur due to the disfiguring character of the facial lesions
and a possible prolonged course of the disease.
[0011] The etiology of perioral dermatitis is unknown. However,
many causative factors have been suggested, including injudicious
use of topical steroids, fluorinated toothpaste, skin care
ointments and creams, especially with a petrolatum or paraffin base
and the vehicle isopropyl myristate, and old or contaminated
make-up or applicators. It is known that UV light, heat and wind
worsen perioral dermatitis. Further, microbials such as fusiform
spirilla bacteria, candida species and other fungi have been found
from the lesions. Other microbiological factors, such as
candidiasis have been reported to provoke perioral dermatitis. In
addition, hormonal factors, and gastrointestinal disturbances have
been considered as well.
[0012] Known treatments include oral tetracyclines, minocin and
doxycycline, with discontinuing topical corticosteroids, and
avoiding lauryl sulfate toothpaste. However, it is currently
believed there is no medicine that one can apply directly to the
skin which will help perioral dermatitis.
[0013] 4. Acneiform eruptions
[0014] Acneiform eruptions are characterized by papules and
pustules resembling acne lesions, not necessarily confined to the
usual sites of acne vulgaris. The eruptions are distinguished by
their sudden onset, usually in a patient well past adolescence.
Most of the acneiform eruptions originate from skin exposure to
various industrial chemicals. Some eruptions may come from oral
medications. Acneiform eruptions may be induced by exposure of the
skin to the fumes generated in the manufacture of chlorine and its
by-products. Cutting oils, lubricating oils, crude coal tar applied
to the skin for medicinal purposes, have tar distillates, coal tar
pitch, and corticosteroids applied to the skin under occlusive
dressings, and asbestos are known substances that may produce
acneiform eruptions. Some of the acneiform eruptions are induced by
medications such as iodides in vitamins with mineral supplement,
and bromides in drugs such as propantheline bromide, and
corticosteroids.
[0015] Although commonly called "trade acne", "bromine acne", and
"chloracne", acneiform eruptions are not a true acne, even though
they are often ushered in by open comedones. Current treatments of
acneiform eruptions include massive keratinization-suppressing
doses of vitamin A, 300,000 units daily, topical retinoids, such as
Retin-A cream or gel, or even oral Accutane.RTM..
[0016] The above-discussed dermatoses are commonly seen clinically.
Some patients respond well to the existing treatments. However,
many patients suffer from the diseases for many years without
significant improvement after being treated with all existing
treatments. Furthermore, some patients have adverse reactions to
the existing medications, or can not tolerate antibiotics used for
treating these dermatoses. Sometimes, it is not appropriate to use
existing treatment methods or medications for certain patients. For
example, antibiotics and Accutane.RTM. are effective for treating
acute inflammation caused by these dermatoses, however, they should
not be used for pregnant women and nursing mothers. Therefore,
there is apparently a need for new and effective topical treatments
for the above-mentioned dermatoses.
[0017] The preferred compound that is used to illustrate the
present invention is ivermectin. Ivermectin is a semi-synthetic
derivative of avermectin and is generally produced as a mixture of
at least 80% 22,23-dihydroavermectin B.sub.1a and less than 20%
22,23-dihydroavermectin B.sub.1b. The following molecular structure
represents the avermectin series of compounds, which can be
chemically converted to useful derivatives as discussed below.
1
[0018] wherein R is the 4'-(alpha-L-oleandrosyl)-alpha-L-oleandrose
group of the structure: 2
[0019] wherein the broken line indicates a single or double bond;
R.sub.1 is hydroxy and is present only when said broken line
indicates a double bond; R.sub.2 is isopropyl or sec-butyl; and
R.sub.3 is methoxy or hydroxy.
[0020] The avermectins, of which ivermectin, a chemically produced
analog, is a member, are a series of compounds isolated from the
fermentation broth of a C-076 producing strain of Streptomyces
avermitillis and also chemically produced derivatives thereof.
There are eight different but closely related compounds are
produced by S. avermitillis, designated as A.sub.1a, A.sub.1b,
A.sub.2a, A.sub.2b, B.sub.1a, B.sub.1b, B.sub.2a, and B.sub.2b. The
production of these compounds is described in U.S. Pat. No.
4,310,519. The preparation of ivermectin is disclosed in U.S. Pat.
No. 4,199,569. The disclosures of each of the foregoing patents are
incorporated herein by reference. The avermectin family of
compounds is a series of very potent antiparasitic agents known to
be useful against a broad spectrum of endoparasites and
ectoparasites in mammals and also to have agricultural uses against
various nematode and insect parasites found in and on crops and in
soil.
[0021] Some of the avermectins contain a 22,23-double bond. This
may be selectively reduced to prepare the ivermectin compounds. In
addition, the avermectins possess a disaccharide moiety at the
13-position consisting of the
alpha-L-oleandrosyl-alpha-L-oleandrosyl group. One or both of these
saccharide groups may be removed as described in U.S. Pat. No.
4,206,205, and the produced aglycone derivatives have a hydroxy
group at the 13-position. This group may be removed to form the
13-deoxy compound as described in U.S. Pat. Nos. 4,171,314 and
4,173,571; the latter patent also describes the 13-halo
derivatives. The avermectin compounds and derivatives have several
hydroxy groups which may be acylated as described in U.S. Pat. No.
4,201,861. U.S. Pat. No. 5,055,454 describes invert position 13 of
avermectin from a normal alpha stereochemistry to the epimeric
13-beta stereochemistry. U.S. Pat. No. 5,077,308 describes
avermectin aglycone derivatives which incorporate a ketal at
position 13. U.S. Pat. No. 5,162,363 describes avermectin
derivatives where te 23-position ring carbon atom is replaced with
by sulfur atom. U.S. Pat. No. 5,229,416 describes avermectin
aglycone derivatives which incorporate two fluorine atoms at
position 13 and 23. U.S. Pat. No. 5,262,400 describes avermectin
compounds that have various substituents at the 4a-position
including alkyl, alkoxy alkyl, or polyalkoxy alkyl groups. Other
derivatives of avermectin and ivermectin are disclosed in U.S. Pat.
Nos. 4,333,925, 4,963,667, 5,114,930, 5,350,742, and 5,830,875. All
the aforementioned patents are incorporated herein by reference.
The compounds disclosed in the patents mentioned above share the
property of antiparasitic activity with ivermectin.
[0022] All avermectin compounds mentioned and referred to above
share the spectrum of anti-parasitic biological activity of
ivermectin, varying only in degree. It is expected that they will
share the activity spectrum of ivermectin needed for them being
suitable to use for the purpose of the present invention.
[0023] Ivermectin has been used as an antiparasitic agent to treat
various animal parasites and parasitic diseases since mid-1980's.
It is commercially available for animal use as Cardomec (for
felines), Eqvalan (for equines) and Ivomec (for bovines) by Merial,
a company of Merck Sharp & Dohme and Aventis. The medicine is
available in tablets and chewables for heartworm prevention,
topical solution for ear mite treatment, or as oral or injectable
solution for other parasite problems.
[0024] Ivermectin is also commercially available from Merck &
Co., Inc for human use as Stromectol.RTM. for eradication of
threadworm Strongyloides stercoralis, and for eradication of
Onchocerca volvulus. Stromectol.RTM. was approved by the U.S. Food
and Drug Administration to treat nondisseminated intestinal
threadworm (strongyloidiasis) in March 1997. Stromectol.RTM. has
also been cleared by the U.S. Food and Drug Administration to treat
onchocerciasis, or river blindness. The medicine is available in
tablets and is orally administered by the patients. The recommended
dose of Stromectol.RTM. for the treatment of intestinal
strongyloidiasis is a single oral dose, two 6 mg tablets for
average weight adults (200 micrograms per kilogram of body weight).
Stromectol.RTM. can also be used in children who weigh 15 kg (33
lb.) or more, at a dose ranging from 1/2 to 2 tablets.
[0025] Magda et al. Amer. J. Trop. Med. Hyg. 53(6) 1995 pp. 652-653
describe a method of topical application of ivermectin to treat
head lice. Ivermectin is found to have an absolute curative effect
after a single topical application.
[0026] U.S. Pat. No. 5,952,372 (to McDaniel) discloses a method of
treating a form of rosacea associated with the ectoparasite Demodex
by orally administering or topically applying ivermectin to fill
and eliminate Demodex Follicuorum mites from hair follicles in
affected skin. Such treatment results in cessation of the
manifestations of allergic and vasomotor responses to the organism
that cause the symptoms and signs of rosacea.
[0027] U.S. Pat. No. 6,133,310 (to Parks) discloses a method of
treating acne rosacea by topically applying ivermectin to the
affected areas. Acne rosacea is a different dermatological disease,
in term of etiology, and/or histology, from transient acantholytic
dermatitis, acne miliaris necrotica, acne varioliformis, perioral
dermatitis, and acneiform eruptions addressed in the present
invention. Differential diagnosis is important for the patients to
obtain an appropriate treatment and effective prevention of their
conditions.
SUMMARY OF THE INVENTION
[0028] Accordingly, it is an object of the invention to provide an
effective topical treatment of transient acantholytic dermatitis,
acne miliaris necrotica, acne varioliformis, perioral dermatitis,
and acneiform eruptions.
[0029] In one embodiment, the present invention relates to a method
of treating a dermatosis comprising topically applying a
therapeutically effective amount of an avermectin compound to an
affected area of a patient. The dermotosis is one disease selected
from the group consisting of transient acantholytic dermatitis,
acne miliaris necrotica, acne varioliformis, perioral dermatitis,
and acneiform eruptions.
[0030] The avermectin compound is in a dermatological composition
comprising an effective amount of the avermectin compound and a
pharmaceutically acceptable carrier including water, glycols,
alcohols, lotions, creams, gels, emulsions, sprays, shampoos,
soaps, body washes, facial cleansers, and facial masks. The
dermatological composition can also be integrated into medicated
tape, topical dressing, dermal patch, or cleansing tissue. The
avermectin compound includes avermectins, avermectin derivatives,
ivermectin and ivermectin derivatives. The concentration of the
avermectin compound in the dermatological composition is from about
0.05% to about 8% (w/v). In a preferred embodiment, ivermectin is
used.
[0031] In a further embodiment, the present invention relates to a
method of treating a dermatosis selected from the group consisting
of transient acantholytic dermatitis, acne miliaris necrotica, acne
varioliformis, perioral dermatitis, and acneiform eruptions
comprising the steps of: (a) topically applying an initial dosage
of an avermectin compound to an affected area of a patient for an
initial treatment period, and (b) thereafter topically applying a
maintenance dosage of an avermectin compound to the affected area
for maintenance.
[0032] In an additional embodiment, the present invention further
relates to a dermatological kit for treating treating transient
acantholytic dermatitis, acne miliaris necrotica, acne
varioliformis, perioral dermatitis, or acneiform eruptions. The kit
includes a dermatological composition comprising avermectin
compound and a pharmaceutically acceptable carrier in a container,
and an insert, on or inside of said container, with instructions on
how to use the dermatological composition for treating transient
acantholytic dermatitis, acne miliaris necrotica, acne
varioliformis, perioral dermatitis, and acneiform eruptions.
DETAILED DESCRIPTION OF THE INVENTION
[0033] The present invention relates to a method of treating
several common dermatoses including transient acantholytic
dermatitis, acne miliaris necrotica, acne varioliformis, perioral
dermatitis, and acneiform eruptions. The method comprises topical
application of a therapeutically effective amount of an avermectin
compound to affected areas of a patient.
[0034] The avermectin compounds for the purpose of the present
invention include avermectin, avermectin derivatives, ivermectin,
and ivermectin derivatives. The avermectin compound is preferably
mixed with a pharmaceutically acceptable carrier or a base which is
suitable for topical application to dermal tissues, to form a
dermatological composition. Suitable examples of carrier or base
include, but not limited to, water, glycols, alcohols, lotions,
creams, gels, emulsions, and sprays. Furthermore, the
dermatological composition containing an avermectin compound can be
integrated into topic dressing, medicated tape, skin patch, also
called dermal patch, and cleansing tissues. Additionally, the
avermectin compound can be added into shampoo, soap, body wash,
facial cleanser, and facial mask. Examples 1 to 3 provide various
topical dermatological compositions containing an avermectin
compound for treatment of the above-referenced dermatoses.
[0035] In a preferred embodiment, ivermectin is used because it is
readily available commercially. The concentration of ivermectin in
the dermatological composition for the purpose of the present
invention can be in a broad range from about 0.05% to 8% weight by
volume (w/v). It has been found that a lotion or a cream containing
ivermectin at a concentration as low as 0.075% is clinically
effective in treating transient acantholytic dermatitis, acne
miliaris necrotica, acne varioliformis, perioral dermatitis, and
acneiform eruptions.
[0036] The treatment method using ivermectin dermatological
composition for each of these dermatoses is similar. Preferably, in
an initial treatment of these dermatoses the ivermectin
dermatological composition can be applied topically from one to
several times daily for a period of from about one week to several
weeks, to substantially control the condition and clear the
lesions. The initial dosage, including frequency of the topical
application, ivermectin concentration of the dermatological
composition, and the length of the initial treatment period can be
determined depending on a specific disease, severity of the
disease, and the response of the patient to the medication. For
example, acne miliaris necrotica is more difficult to treat, and it
frequently requires an initial treatment of three weeks or longer.
While perioral dermatitis patients can respond to ivermectin
treatment rapidly, and healing of lesions can occur in less than
two weeks. After the initial treatment, a maintenance dosage, that
has less frequent application, and/or a dermatological composition
with less concentration of ivermectin, can be used for maintaining
the condition.
[0037] It has been found in an informal clinical trial using the
method of the present invention that topical application of
ivermectin to skin affected by transient acantholytic dermatitis,
acne miliaris necrotica, acne varioliformis, perioral dermatitis,
or acneiform eruptions has the following advantageous properties:
(1) it removes itching and skin irritation caused by these
dermatoses; (2) it clears up lesions; (3) it is anti-inflammatory
and controls inflammation of the affected area; (4) it has
antimicrobial property and controls dermal infection of the
affected area; and (5) it is safe and has no side effects observed
in any body locations.
[0038] The choice of the ivermectin concentration, and the form of
the dermatological composition for treatment of a particular
condition of the above-referenced dermatoses can be made depending
on the type and severity of the diseases, location of the affected
area, and form of the dermatological composition.
[0039] To treat most patients diagnosed with one of the
above-mentioned dermatoses, a lotion containing about 0.05% to 0.2%
of ivermectin can be used. In the case of treating acute
conditions, a more potent composition containing higher
concentration of ivermectin can be used. On the other hand, for
prolonged maintenance of certain conditions, a low concentration
such as from about 0.05% to about 0.1% is preferred. Further, a low
concentration of ivermectin should be used for pediatric
patients.
[0040] It is known that some of the diseases, such as perioral
dermatitis, the skin on the eyelids can be affected. To treat
eyelids, a high concentration of the medicine should be avoided to
prevent irritation of the eyes. It is found that a 0.075%
ivermectin lotion does not cause eye irritation when it is used on
the face, around the eyes, or directly on the eyelids.
[0041] In the form of shampoo, soap, facial cleanser, and facial
mask the concentration of ivermectin is higher, such as about 2% to
about 8%, because the medicine is not retained on the skin after
rinsing, and treatment time is short. On the contrary, in the forms
of topic dressing, medicated tape, and dermal patch the medicine
stays on the treated area longer than other forms, therefore, the
concentration of ivermectin can be lower.
[0042] The ivermectin shampoo is an appropriate form for treating
transient acantholytic dermatitis, acne miliaris necrotica and acne
varioliformis, when the affected area is on the scalp. The
medicated shampoo can be particularly suitable for maintenance
treatment, or prevention of break out for the patients who have
chronical history of these diseases.
[0043] Optionally, a combination of different forms of topical
treatment can also be used. For example, an ivermectin tape can be
used in the night, and an ivermectin cream or lotion can be used
during the day. The ivermectin shampoo, soap, facial cleanser, and
facial mask can be used in combination with any of other topical
applications.
[0044] The dermatological composition containing ivermectin can be
sold as a kit wherein the composition is packaged in a container,
such as a plastic container. Instructions on how to use the
dermatological composition in accordance with the present invention
are included on or associated with the container, which provides
detailed instructions for treating transient acantholytic
dermatitis, acne miliaris necrotica, acne varioliformis, perioral
dermatitis, or acneiform eruptions.
[0045] Although the inventor is not bound by any theoretical
explanation as to why the composition and the method of the present
invention are effective in treating transient acantholytic
dermatitis, acne miliaris necrotica, acne varioliformis, perioral
dermatitis, or acneiform eruptions, presentation of certain
theoretical understanding may be of value. Based on the clinical
observations, it is believed that one reason for the efficacy of
the composition and the method of the present invention is due in
part to anti-microbial property of ivermectin.
[0046] Another possible reason for the efficacy of the composition
and the method of the present invention is that the ivermectin
dermatological composition has anti-inflammatory effect. It is
believed that ivermectin exerts an anti-inflammatory effect on the
cells of the sebaceous gland unit, thus decreasing production of
neutrophils and lymphocytes which contribute to inflammation.
[0047] Ivermectin has been used as an oral medication for treatment
of river blindness in human caused by Onchocerca volvulus parasite
since late 1980s. With an oral dosage of a moderate ivermectin
concentration, this medicine is safe in human, without serious
adverse side effects. Therefore, topical treatment of dermatoses
using ivermectin dermatological composition and the method of the
present invention is safe to human patients, which was demonstrated
by the clinical examples described hereinafter. Furthermore, as
discussed previously that a dermatological composition having
ivermectin concentration as low as 0.075% is clinically effective
in treating transient acantholytic dermatitis, acne miliaris
necrotica, acne varioliformis, perioral dermatitis, and acneiform
eruptions. Such a low concentration is advantageous because it
reduces risks of adverse side effects, and reduces the possibility
of triggering body's autoimmune responses.
[0048] Operating with the informed consent of the patients who had
suffered from one of the above-mentioned dermatoses, and their
conditions had failed to improve by using existing treatment
methods or were not appropriate to use existing medications, the
patients were treated with the ivermectin dermatological
composition and the method of the present invention. Examples 4 to
12 illustrate clinical effectiveness of the method of the present
invention.
EXAMPLE 1
[0049] A topical dermatological composition containing avermectin
compound is obtained as follows.
[0050] Mix 0.15 g of ivermectin, manufactured by Merck & Co.,
Inc., sufficiently with 100 ml of deionized water to make an
aqueous suspension, wherein the concentration of ivermectin is
0.15% (w/v). Sodium hydroxide and citric acid can be used to
adjusted pH of the suspension to about 7.
[0051] Other suitable composition can be made in accordance with
Example 1 which include ivermectin in the following concentrations:
0.05%, 0.075%, 0.2%, 0.5%, and 1% (w/v).
EXAMPLE 2
[0052] A topical dermatological lotion containing avermectin
compound is obtained as follows.
[0053] Mix 0.075 g of ivermectin, manufactured by Merck & Co.,
Inc., sufficiently with 100 ml of Cetaphil.RTM. moisturizing
lotion, manufactured by Galderma Laboratories, Inc., to make an
ivermectin lotion, wherein the concentration of ivermectin is
0.075% (w/v).
[0054] Other suitable compositions can be made in accordance with
Example 2 which include ivermectin in the following concentrations:
0.05%, 0.1%, 0.2%, 0.5%, 1%, 4%, and 8% (w/v) in the base of
Cetaphil.RTM. moisturizing lotion. Other compatible commercial
available lotions can also be used as a base or carrier.
[0055] The Cetaphil.RTM. moisturizing lotion is a carrier of the
ivermectin, which contains purified water, glycerin, hydrogenated
polyisobutene, cetearyl alcohol and ceteareth-20, macadamia nut
oil, dimethicone, tocopheryl acetate, stearoxytrimethylsilane and
stearyl alcohol, panthenol, farnesol, benzyl alcohol,
phenoxyethanol, acrylates/C10-30 alkyl acrylate crosspolymer,
sodium hydroxide, citric acid.
EXAMPLE 3
[0056] A medicated shampoo containing avermectin compound is
obtained as follows.
[0057] Mix 3 g of ivermectin, manufactured by Merck & Co.,
Inc., sufficiently with 100 ml of a shampoo to make an ivermectin
shampoo, wherein the concentration of ivermectin is 3% (w/v).
[0058] Other suitable compositions can be made in accordance with
Example 3 which include ivermectin in the following concentrations
of 2% 5%, and 8% (w/v) in a base of shampoo.
EXAMPLE 4
[0059] A 76 year old male patient presented with several week
history of pruritic papules on his chest and back. Topical steroids
had no effect. A biopsy showed a papule with mild lymphocytic
infiltration and focal areas of epidermal acantholysis. The patient
was diagnosed with transient acantholytic dermatosis.
[0060] The patient was treated with topical application of the
0.075% ivermectin lotion of Example 2 once to twice daily to wet
skin for two weeks, followed with topical application of the lotion
once or twice weekly at bed time. The patient was also instructed
to stop soap bath, and use weak acetic acids to double rinse
clothes to remove all soap. The patient's condition improved
significantly in three weeks. The patient was instructed to
continue the topical application of the lotion once weekly as
needed. In an over two year follow up, the patient had maintained
remained symptom free.
EXAMPLE 5
[0061] A 63 year old male patient suffered "itchy red bumps" on
chest and back persisting for several months. Topical cortisone did
not improve the condition. Physical examination found pink to red
smooth papules on the chest and back. A biopsy showed only
lymphocytic dermal inflammation, no acantholysis was found. The
patient was diagnosed with transient acantholytic dermatosis. The
patient was treated with topical application of the 0.075%
ivermectin lotion of Example 2 twice daily for ten days, followed
by twice weekly. The patient had nearly total clearing at his four
week follow up visit.
EXAMPLE 6
[0062] A 60 year old male had more than fifteen years history of
tender "pimples" and sores of the vertex scalp. Many past
therapies, including medicated shampoos, oral and topical
antibiotics, were of little or no effect. Physical examination
found vesico-pustules, crusts and thinning hair on the vertex
scalp. The patient was diagnosed with acne miliaris necrotic.
[0063] The patient was treated with topically application of the
0.075% ivermectin lotion of Example 2 daily at bed time for three
weeks, with a decreased sugar consumption in his diet.
[0064] The patient had no new lesions since the first week of
treatment. After three weeks treatment, all old lesions were
completely healed.
EXAMPLE 7
[0065] A 50 year old male patient had a long history of tender
sores on the vertex scalp, associated with hair loss. Physical
examination found typical vesico pustules of acne miliaris of the
vertex scalp, in addition to crusts, excoriations and thinning
hair.
[0066] The patient was treated topically with the 0.075% ivermectin
lotion of Example 2 at bed time for three weeks. The patient's
affected skin was totally cleared in three weeks. A maintenance
dose of topically applying the ivermectin lotion twice weekly was
suggested to the patient for maintenance.
EXAMPLE 8
[0067] A 35 year old female patient had five year history of scalp
tenderness, associated with tender papules. Many prior therapies
failed to treat the condition. The patient was diagnosed with acne
miliaris necrotica on the dorsal and vertex scalp.
[0068] The patient was treated topically with the 0.075% ivermectin
lotion of Example 2 daily at bed time, and washed out in the
morning for three weeks. Three weeks later, all lesions were
healed.
EXAMPLE 9
[0069] A 33 year old female patient had six month history of
perioral dermatitis, which had its onset during the patient's
pregnancy. Previous treatment was withheld because of her
pregnancy. At the time of her first visit after the delivery, she
was nursing the newborn baby and had transmitted the dermatitis to
the baby's lip.
[0070] In lieu of using antibiotics because the mother was nursing,
a treatment of topical application of the 0.075% ivermectin lotion
of Example 2 was given to both mother and the infant daily at bed
time for two weeks. Thereafter, the treatment was reduced to twice
weekly. In three weeks, the baby had a total clearing, and
discontinued the treatment. The mother had near total clearing, and
continued the treatment twice weekly for another three months to
insure healing.
EXAMPLE 10
[0071] A 68 year old male patient with persistent perioral scaly
papules, was diagnosed with perioral dermatitis. Previously, the
patient had adverse reactions to the standard topicals used in this
condition, such as benzoyl peroxide, sulfacetamide, Metrogel.RTM.
from Galderma Laboratories, Inc., and others. In addition, the
patient did not tolerate oral antibiotics.
[0072] The patient was treated with topical application of the
0.075% ivermectin lotion of Example 2 daily for two weeks. After
two weeks, the patient had a total clearing except mild residual
erythema, he was ecstatic with the results achieved.
EXAMPLE 11
[0073] A 35 year old female patient had a many year history of
firm, tender, or mildly pruritic papulo-nodules on the checks and
chin. Past treatments, for acne, were totally ineffective. The
patient was diagnosed with acneiform eruptions without specific
etiology. The patient had no iodine or bromine exposure.
[0074] The patient was treated with topical application of the
0.075% ivermectin lotion of Example 2 daily at bed time for two
weeks, plus elimination of caffeine intake. Thereafter, the dose
was reduced to topical application of the lotion twice a week.
After four weeks, the patient had near total clearing of the
lesions.
EXAMPLE 12
[0075] A 36 year old female patient had a many year history of firm
annoying pink nodules of the face. The patient had no history of
halogen use. This patient previously used numerous acne lotions and
oral tetracycline without effect. The patient was diagnosed with
acneiform eruptions.
[0076] The patient was treated with topical application of the
0.075% ivermectin lotion of Example 2 daily at bed time for two
weeks, followed with topical application of the lotion twice a
week. At the four week return visit, the patient had a total
clearing of the lesions.
[0077] In the informal trials, no adverse side effects or
contra-indications were observed among the patients. The patients
had no complaints of skin irritation during the initial treatment,
or prolonged maintenance treatment. There was no report of
increasing skin sensitivity. For the patients who applied the
ivermectin lotion topically on the eyelids where the lesions were,
there was no eye irritation observed.
[0078] While there has been shown and described the preferred
embodiment of the instant invention it is to be appreciated that
the invention may be embodied otherwise than is herein specifically
shown and described and that, within said embodiment, certain
changes may be made in the form and arrangement of the parts
without departing from the underlying ideas or principles of this
invention as set forth in the claims appended herewith.
* * * * *