U.S. patent application number 09/988914 was filed with the patent office on 2002-05-23 for method of treating acne vulgaris using avermectin compound.
Invention is credited to Parks, L. Dean.
Application Number | 20020061855 09/988914 |
Document ID | / |
Family ID | 27130590 |
Filed Date | 2002-05-23 |
United States Patent
Application |
20020061855 |
Kind Code |
A1 |
Parks, L. Dean |
May 23, 2002 |
Method of treating acne vulgaris using avermectin compound
Abstract
Methods for treating acne vulgaris are disclosed. The treatment
includes topical application of a dermatological composition
containing an avermectin compound to the affected areas of a
patient alone, or in conjunction with other conventional methods of
treating acne vulgaris. The dermatological composition contains an
avermectin compound in a pharmaceutically acceptable carrier,
including water, glycols, alcohols, lotions, creams, gels,
emulsions, sprays, soaps, body washes, facial cleansers, and facial
masks.
Inventors: |
Parks, L. Dean; (Ocala,
FL) |
Correspondence
Address: |
Melvin K. Silverman
Suite 440
4901 North federal Highway
Fort Lauderdale
FL
33308
US
|
Family ID: |
27130590 |
Appl. No.: |
09/988914 |
Filed: |
November 19, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09988914 |
Nov 19, 2001 |
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09976915 |
Oct 12, 2001 |
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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 |
Current CPC
Class: |
Y10S 514/859 20130101;
A61K 8/498 20130101; A61K 31/704 20130101; A61K 31/35 20130101;
A61Q 19/10 20130101; A61P 17/10 20180101; A61Q 19/00 20130101 |
Class at
Publication: |
514/28 |
International
Class: |
A61K 031/7048 |
Claims
What is claimed is:
1. A method of treating acne comprising topically applying a
therapeutically effective amount of an avermectin compound to an
affected area of a patient.
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, 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%.
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%.
8. A method of treating acne vulgaris 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.
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 acne vulgaris comprising topically
applying a therapeutically effective amount of ivermectin to an
affected area of a patient.
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, 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%.
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%.
17. A method of treating acne vulgaris 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.
18. The method of claim 17, wherein said initial treatment period
is from about one week to several weeks.
19. A method of treating acne vulgaris comprising: (a) topically
applying to the affected areas of the patient a therapeutically
effective amount of avermectin compound, and (b) administering to a
patient a therapeutically effective amount of at least one other
anti-acne medication.
20. The method of claim 19, wherein said at least one other
anti-acne medication comprises benzoyl peroxide, sulfur,
resorcinol, salicyclic acid, opioid, tretinoin, antibiotics, and
isotretinoin.
21. The method of claim 19, wherein said avermectin compound
comprises avermectins, avermectin derivatives, ivermectin, or
ivermectin derivatives.
22. The method of claim 21, wherein said avermectin compound is in
a dermatological composition comprising said avermectin compound in
a concentration greater than about 0.05%, and a pharmaceutically
acceptable carrier.
23. A kit for treating acne vulgaris comprising: (a) a
dermatological composition in a container, said dermatological
composition comprising an avermectin compound and a
pharmaceutically acceptable carrier, and (b) instructions on or
associated with said container on how to use said dermatological
composition for treating acne vulgaris.
24. The kit of claim 23, wherein said avermectin compound comprises
avermectins, avermectin derivatives, ivermectin, or ivermectin
derivatives.
Description
REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of co-pending
patent application Ser. No. 09/976,915 entitled "Method of Treating
Dermatoses Using Avermectin Compound" filed on Oct. 12, 2001, which
is a continuation-in-part of co-pending application Ser. No.
09/605,747 filed on Jun. 29, 2000, both of which are herein
incorporated by reference in their entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to methods for treating acne
vulgaris, particularly with topical treatment using avermectin
compound.
BACKGROUND OF THE INVENTION
[0003] Acne vulgaris, known as acne by the general public, is a
common and multifaceted skin disorder of the hair follicles and
sebaceous glands. Although it affects almost 100% of adolescents to
varying degrees and generally wanes as adolescence ends, the
disease may persist into adulthood. Adult women, in particular, may
be affected and may experience premenstrual flares. However, severe
acne vulgaris tends to be more common in adolescent males than in
people of other age-groups.
[0004] At least four factors contribute to the development of acne:
follicular plugging, increased sebum production by the sebaceous
glands, colonization of the sebaceous follicles with
Propionibacterium acnes, and inflammation. Propionibacterium acnes
is the most common gram-positive, non-spore forming bacteria, a
common resident of the pilosebaceous glands of the human skin. It
is the causative agent of acne vulgaris.
[0005] Follicular plugging occurs when desquamating cells lining
the follicular lumen stick together, rather than flowing to the
surface with sebum. This occurs because of abnormal keratinization,
components of which are increased cell division and increased
cohesiveness of cells lining the follicular lumen. These cells mix
with sebum, plug the opening of the hair follicle, and form a
closed comedo (commonly called whitehead). If this mixture
protrudes from the follicular opening, it turns a dark color
(blackheads).
[0006] During adolescence, when sebum production increases, the
sebaceous follicles become colonized with Propionibacterium acnes.
This anaerobic diphtheroid hydrolyzes sebum into free fatty acids,
which serve as the primary proinflammatory substances of acne
vulgaris. Propionibacterium acnes also secrete chemotactic factors
that attract neutrophils. Lysosomal enzyme released from the
neutrophils rupture the follicle wall releasing proinflammatory
mediators including keratin and lipids into the surrounding dermis.
The resulting inflammation forms erythematous papules or pustules,
nodules, cysts, or abscesses. If the inflammation is severe, as in
cystic acne, the skin may eventually scar.
[0007] Therefore, the key features of the pathogenesis of acne
vulgaris can be characterized as 1) increased sebum production, 2)
hyperkeratinization of the neck of the follicles, 3) bacterial
proliferation, and 4) inflammation.
[0008] Acne vulgaris can be classified into three categories:
comedonal, inflammatory, and nodulocystc. Within each category,
acne vulgaris can be further divided into mild, moderate, or
severe, based on the number of lesions and the amount of skin
involved.
[0009] Comedonal acne consists predominantly of open or closed
comedones with generally few, if any, inflammatory lesions.
Comedonal acne generally responds to existing topical keratolytic
agents, which decrease the adhesiveness of follicular cells.
Inflammatory acne consists of comedonal lesions plus inflammatory
lesions, such as erythematous papules and pustules. It generally
requires treatment with both topical agents and systemic
antibiotics. By comparison, nodulocystic acne comprises extensive
comedonal lesions and inflammatory papules and pustules, plus
nodules and cysts or abscesses. Existing topical agents are not
effective for initial treatment of these lesions.
[0010] Effective management of acne vulgaris can be accomplished by
addressing the four key features of the pathogenesis. Topical
therapy is usually the first choice for patients with
mild-to-moderate inflammatory acne. The use of topical therapy
minimizes potential side effects associated with the use of
systemic agents. Topical therapies include benzoyl peroxide, which
is the most commonly used non-prescription acne medication. It is
an important antibacterial oxidizing agent that can decrease the
number of Propionibacterium acnes and frequently the amount of free
fatty acids. Benzoyl peroxide is the first line monotherapy for
mild acne vulgaris and it is available in over-the-counter
preparations. Benzoyl peroxide is applied once or twice daily and
patients often experience mild redness and scaling of the skin
during the first week of usage.
[0011] Tretinoin is the most effective topical comedolytic agent
currently, decreasing the cohesiveness of follicular epithelial
cells, and thereby inhibiting the formation of microcomedones and
increasing cell turnover resulting in expulsion of existing
comedones. This agent also decreases the thickness of the stratum
corneum and potentiates the penetration of topical antibiotic
agents. Tretinoin therapy comprises once daily application. Mild
redness and peeling are a part of the therapeutic effect of the
medication but can result in reduced patient compliance. The
improvement may take as long as 6 to 12 weeks, and flare-ups of
acne vulgaris can occur during the first few weeks of therapy.
[0012] Mild inflammatory acne vulgaris lesions can also be treated
with topical antibiotics including erythromycin ointment,
clindamycin solution, and meclocylcine cream. The primary action of
the antibiotics is to reduce the population of Propionibacterium
acnes in the sebaceous follicle and thereby suppress the free fatty
acid production. The effectiveness of topical antibiotics in the
treatment of acne is limited by their low lipid solubility and
subsequent difficulty in penetrating sebum-filled follicles.
Topical antibiotics are applied twice daily.
[0013] Patients with moderate to severe inflammatory acne often
require oral antibiotics in addition to topical therapy. The most
commonly prescribed agents include tetracycline, erythromycin,
minocycline, and doxycycline. Treatment is usually maintained for
several months. Side effects include the overgrowth of
nonsusceptible organisms, including Candida, which can produce
vaginal and oral yeast infections.
[0014] Patients with severe inflammatory acne vulgaris unresponsive
to other therapy may require treatment with oral isotretinoin.
Isotretinoin is a compound related to vitamin A, and is the only
agent that decreases sebum production and reverses the abnormal
epithelial formation process. This agent can also decrease number
of Propionibactemum acnes in the sebaceous follicle. Duration of
therapy is usually 20 weeks, and the satisfactory response rate is
quite high. However, treatment is often accompanied by many side
effects, including dry skin, pruritus, epistaxis, and
photosensitivity, as well as hypertriglyceridemia, abnormal liver
function tests, electrolyte imbalances, and elevated platelet
counts. Most serious though, is the teratogeric effect of
isotretinoin. Use of isotretinoin during pregnancy is absolutely
contraindicated. So serious is the potential for death or
teratogenic effects to a fetus, isotretinoin is practically
contraindicated in women of child-bearing age. Use of isotretinoin
must be accompanied by a guarantee by the patient that conception
will be avoided at any and all costs.
[0015] Because acne vulgaris is a multifactorial disease which is
manifest to varying degrees, it is important for the physician to
assess the patient to attempt to find therapies which will be
helpful to the patient without causing major side effects. All of
the current conventional treatments are associated with some degree
of adverse side effects that limit their usefulness. Consequently,
there is a need for a drug that can effectively treat acne vulgaris
without side effects.
[0016] 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
[0017] wherein R is the 4'-(alpha-L-oleandrosyl)-alpha-L-oleandrose
group of the structure: 2
[0018] 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.
[0019] 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 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.
[0020] 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 inverting 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 the 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.
[0021] 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.
[0022] 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.RTM. (for
felines), Eqvalan.RTM. (for equines) and Ivomec.RTM. (for bovines)
by Merial, a Merck and Aventis company; as Zimecterin.RTM. (for
equines) by Famam Companies, Inc., Omaha, Nebr. The medicine is
available in tablets and chewables for heartworm prevention,
topical solution for ear mite treatment, and injectable solution,
or oral paste or solution for other parasite problems.
[0023] 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
onchocerdasis, 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.
[0024] 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.
[0025] U.S. Pat. No. 5,952,372 (to McDaniel) disdoses 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.
[0026] U.S. Pat. No. 6,133,310 (to Parks) discioses 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 histology, from acne vulgaris which is
addressed in the present invention. Differential diagnosis is
appropriate treatment and effective prevention of their
conditions.
SUMMARY OF THE INVENTION
[0027] Accordingly, it is an object of the invention to provide an
effective topical treatment of acne vulgaris.
[0028] In one embodiment, the present invention relates to a method
of treating acne vulgaris comprising topically applying a
therapeutically effective amount of an avermectin compound to an
affected area of a patient.
[0029] 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, 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, preferably
ivermectin and ivermectin derivatives. The concentration of the
avermectin compound in the dermatological composition is from about
0.05% to about 8% (w/v, or w/w). In a preferred embodiment,
ivermectin is used.
[0030] In a further embodiment, the present invention relates to a
method of treating acne vulgaris 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.
[0031] In an additional embodiment, the present invention further
relates to a dermatological kit for treating acne vulgaris. The kit
includes a dermatological composition comprising avermectin
compound and a pharmaceutically acceptable carrier in a container,
and written instructions on or associated with the container, on
how to use the dermatological composition for treating acne
vulgaris.
DETAILED DESCRIPTION OF THE INVENTION
[0032] The present invention relates to a method of treating acne
vulgaris. In one embodiment, the method comprises topical
application of a therapeutically effective amount of an avermectin
compound to affected areas of a patient.
[0033] 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 skin, 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 a topical
dressing, medicated tape, dermal patch and cleansing tissues.
Additionally, the avermectin compound can be added into soap, body
wash, facial cleanser, and facial mask. Examples 1 to 3 provide
various topical dermatological compositions containing an
avermectin compound for treatment acne vulgaris.
[0034] 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), or weight by weight (w/w) depending on the form of
the carrier. When the carrier is water, measuring by volume is
convenient. However, when the carrier is gel or cream, measuring by
weight is more convenient. 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 acne vulgaris.
[0035] Preferably, in an initial treatment of acne vulgaris 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 (for example, two to six weeks), to substantially
control the condition and dear 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 type of acne vulgaris, severity of the disease, and the
response of the patient to the medication. 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.
[0036] 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 acne vulgaris has the following
advantageous properties: (1) it removes skin irritation caused by
acne vulgaris; (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.
[0037] The choice of the ivermectin concentration, and the form of
the dermatological composition for treatment of acne vulgaris can
be made depending on the type of acne vulgaris and severity of the
diseases, location of the affected area, and form of the
dermatological composition.
[0038] To treat most patients diagnosed with acne vulgaris, 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.
[0039] Acne vulgaris can occur near the eyes, such as on the eye
brows. To treat skin near eyes, 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, or near the eyes.
[0040] In the form of body wash, 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.
[0041] 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 body wash, soap, facial cleanser,
and facial mask can be used in combination with any of other
topical applications.
[0042] The dermatological composition containing ivermectin can be
sold as a kit wherein the composition is packaged in a container,
such as a plastic container. Written instructions on how to use the
dermatological composition in accordance with the present invention
are included on or associated with the container, which provides
instructions for treating acne vulgaris.
[0043] 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 acne vulgaris, 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.
[0044] 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.
[0045] 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 acne vulgaris
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 acne vulgaris. Such a low concentration is advantageous
because it reduces risks of adverse side effects, and reduces the
possibility of triggering body's autoimmune responses.
[0046] In a further embodiment, the present invention relates to a
method of treating acne vulgaris which comprises (a) topically
applying to the affected areas of the patient a therapeutically
effective amount of avermectin compound; (b) administering to a
patient a therapeutically effective amount of at least one other
conventional anti-acne medication, which includes, but not limited
to, benzoyl peroxide, sulfur, resorcinol, salicyclic acid, opioid,
tretinoin, antibiotics, and isotretinoin. The conventional
medications should be used in conventional doses. In this case, the
avermectin compound is used in conjunction with conventional acne
treatment as an adjuvant. The combinational treatment is beneficial
for treating a multifactorial disease like acne vulgaris.
[0047] Operating with the informed consent of the patients who had
suffered from acne vulgaris, 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 and 5 illustrate clinical effectiveness of
the method of the present invention.
EXAMPLE 1
[0048] A topical dermatological composition containing avermectin
compound is obtained as follows
[0049] 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.
[0050] 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
[0051] A topical dermatological lotion containing avermectin
compound is obtained as follows.
[0052] 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., Fort Worth,
Tex., to make an ivermectin lotion, wherein the concentration of
ivermectin is 0.075% (w/v).
[0053] 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 or w/w) in the base of
Cetaphil.RTM. moisturizing lotion. Other compatible commercial
available lotions can also be used as a base or carrier.
[0054] 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, famesol, benzyl alcohol,
phenoxyethanol, acrylates/C10-30 alkyl acrylate crosspolymer,
sodium hydroxide, citric acid.
EXAMPLE 3
[0055] A medicated body wash containing an avermectin compound is
obtained as follows.
[0056] Mix 5 g of ivermectin, manufactured by Merck & Co.,
Inc., sufficiently with 100 ml of a body wash liquid to make an
ivermectin body wash, wherein the concentration of ivermectin is 5%
(w/v).
[0057] Other suitable compositions can be made in accordance with
Example 3 which include ivermectin in the following concentrations
of 1%, 3%, and 8% (w/v or w/w) in a base of body wash. The body
wash base can be a solution, a gel, or an emulsion.
EXAMPLE 4
[0058] A 20 year old pregnant woman developed pustulocystic acne,
one type of acne vulgaris, during the latter months of pregnancy.
Therapy was limited to topical treatment including benzoyl
peroxide, Retin-A (tretinoin), and hydrocortisone lotion. In spite
of these treatments, her condition continued to worsen even after
delivery. The patient had two large cysts on the right cheek which
her physician had scheduled for surgery. Oral antibiotics were not
a choice of treatment because she was nursing.
[0059] The patient was treated with topical application of the
0.075% ivermectin lotion of Example 2 daily at bed time. In three
weeks, her condition improved substantially, and the "cyst surgery"
was cancelled because it was no longer needed. A maintenance dosage
of topical application of the lotion twice a week was instituted
thereafter for four weeks, and the patient had a total
clearing.
EXAMPLE 5
[0060] A 12 year old girl had extensive comedo-pustular acne
(another type of acne vulgaris) on the brow, nose and malar areas.
She was treated with Retin-A and benzoyl peroxide. The patient was
very distraught because of the redness, inflammation and
pustulation. For this reason she was treated with topical
application of the 0.075% ivermectin lotion of Example 2 once to
twice daily, in addition to her existing conventional treatments.
Within two weeks, all of the redness and pustules were gone.
Retin-A therapy was continued to the residual comedones.
[0061] 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.
[0062] 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.
* * * * *