Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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TITLE OF INVENTION
Gel suitable for use in the treatment of rosacea and acne.
5 FIELD OF INVENTION
This invention relates to the treatment of rosacea and acne. In some
embodiments this invention also finds application not only to the topical treatment
of the skin due to a disease including rosacea, but also to diseases or conditions
like erythemia, telangiectasia and inflammatory lesions, and the reduction of
10 papule and pustule count as well.
This invention also relates to compositions preferably comprising
metronidazole suitable for use in such treatments, the use of such formulations, the
use of metronidazole and methods of carrying out such treatments.
BACKGROUND OF THE INVENTION
Rosacea is a chronic, dermatologic disease (inflammatory disorder)
characterized by redness and telangiectasia of the face and punctuated by
episodes of inflammation and recurrent crops of papules and pustules, and
20 swelling as well. The pathogenesis (etiology) is unknown. Therapy usually
involves administration of an oral antibiotic. Metronidazole has been administered
orally and has been shown to be as effective as tetracycline in the treatment ofrosacea.
However, concerns over possible toxicity associated with long term
therapy prompted the development of topical formulations such as 1% cream,
0.75% water based gel, and even a 5% topical suspension.
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For example, Vehicle Effect on Topical Drug Delivery Mollgaard et al.
Acta. Pharm. Svec. Vol. 20, No. 6, 1983, purports to teach on pages 448-450, a
Metronidazole carbopol aqueous gel which contains propylene glycol.
French Patent Publication No. 2,558,058, published on July 19, 1985,
purports to teach on pages 3, 4, and 5, the use of Metronidazole in topical form,
together with other ingredients in the treatment of acne. Pages 7 and 8 thereof
purports to teach several types of bases which may be incorporated with
Metronidazole, i.e. "One type of support may for example be constituted principally
by the combination of 20 to 70% by volume of ethyl alcohol, the balance being
found by water, glycerol, a polyol such as ethylene glycol, propylene glycol or their
oxyethylene homologues alone in mixture:
The publication also provides:
"In one preferred embodiment of the invention, the base is constituted
by an 'équipondéral' mixture of ethyl alcohol and polyethylene glycol.
It can also be equally associated with in small quantities, less than
10% of the total composition, ketones such as methylisobutyl ketone,
alcohol esters like ethyl acetate as ethers like dimethoxymethane,
which permits contribution of the known effect without causing any
disagreeable effects to the skin.
Furthermore, the dermatological compositions may contain other
additions such as preservatives, perfumes, colouring agents, as
would be expected in formulations of such compositions.
3 2 ~ ~ ~ 7 ~ ~
The dermatological compositions for external topical
application can be introduced in the form of solutions, lotions, gels or
creams. The solutions, gels or lotions may be conditioned in the
classical manners in the form of flakes, aerosols or ampoules".
U.S. Patent 4,247,547, issued on January 27, 1981, purports to teach
the use of hydroxy propyl cellulose as a gelling agent (column 4, line 12-13) and
also the use of an acidic carboxy polymer, i.e. CarbopolTM 940 as a gelling agent
(column 4, line 14-15). It also purports to teach the use of an organic solvent in a
10 gel formulation i.e. ethanol (absolute or 95% by volume ethyl alcohol), isopropanol,
propylene glycol and combination thereof in a gel formulation for treating acne.
U.S. Patent 3,883,661, issued on May 13, 1975, purports to teach the
use of hydrous or anhydrous gels with carbopols as gelling agents in the use with
15 fatty acid amides in the treatment of acne.
The article entitled Metronidazole Suspension Applied Topically for
Rosacea British Journal of Dermatology (1084) Ill, 499-502 purports to teach theuse of metronidazole in a suspension for topical skin application in the treatment of
20 rosacea.
Doring, H.F., et al., Z. Hautkr., Vol. 58, No. 3, pp 141-155 (1983)
purports to teach the use of Metronidazole in the treatment of rosacea.
However, none of these formulations took into account that the sun, among other
environmental factors like the wind or cold, could produce a dermal dystrophy ininherently susceptible individuals which could be the source of the symptoms
observed in rosacea (see Marks et al, Rosacea and Perioral Dermatitis from:
4 2161737
from: Textbook of Dermatology 4th ed. by Rooks et al 1986; Chapter 40: 1605-
161 1). Several papers report that patients with rosacea complained that exposure
to sun made their condition worse.
Since it is well established that sunlight makes rosacea worse, it
would be beneficial to patients with rosacea to apply sunscreens to block the UVradiation from damaging the skin further by exacerbating rosacea.
It is therefore an object of the invention to provide a topical
composition for the treatment of rosacea which includes sunscreens to block UV
radiation from damaging the skin further, preferably the sunscreen blocks UV-A and
UV-B radiation.
It is also another object of the invention to provide a method of treating
rosacea where said method of treatment also includes a sunscreen to block
radiation.
It is also another object of the invention to provide a composition that
is effective against telangiectasia, and against papules and pustules.
It is also another object of the invention to provide a composition in
one embodiment which is substantially in an alcohol base gel exhibiting
bactericidal qualities.
It is a further object of the invention to provide such composition which
because of the use of an alcohol base, minimizes any stinging effect and preferably
substantially has no stinging effect.
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Further and other objects and benefits of the invention will be realized
by those skilled in the art from the disclosure and the accompanying claims.
SUMMARY OF THE INVENTION
Thus, according to one aspect of the invention there is provided a
topical composition for the treatment of rosacea and acne comprising:
(a) an effective amount of metronidazole or salt thereof;
(b) an effective amount of at least one sunscreen compatible with said
metronidazole; and
(c) a suitable vehicle, preferably a substantially alcoholic base.
According to another aspect of the invention there is provided a
topical composition suitable for the treatment of rosacea and acne
comprising:
(a) an effective amount of an antibiotic; preferably metronidazole
(b) an effective amount of a sunscreen; preferably selected from the
group consisting of octyl methoxycinnamate and butyl methoxydibenzoyl methane
(c) an effective amount of an emollient; preferably selected from the
group consisting of dioctyl maleate and isoarachidyl neopentanoate
(d) an effective amount of a lubricant; preferably cyclomethicone
(e) an effective amount of a gelling agent; preferably hydroxypropyl
cellulose, and
(fl an effective amount of a pharmaceutically acceptable diluent or
carrier for the above, preferably isopropyl alcohol 99% USP.
According to yet another aspect of the invention there is provided a
substantially topical gel composition for the treatment of rosacea comprising:
(a) an effective non-toxic amount of an antibiotic; preferably
metronidazole
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(b) an effective non-toxic amount of a sunscreen; preferably selected from
the group consiting of octyl methoxy cinnamate and butyl methoxydibenzoyl
methane
(c) an effective non-toxic amount of an emollient; preferably selected from
5 the group consisting of dioctyl maleate and isoarachidyl neopentanoate
(d) an effective non-toxic amount of a lubricant; preferably
cyclomethicone
(e) an effective non-toxic amount of a gelling agent; preferably
hydroxypropyl cellulose, and~0
(f) an effective amount of a pharmaceutically acceptable diluent or
carrier; preferably isopropyl alcohol 99% USP. .
According to yet another aspect of the invention there is provided you
missed (in one embodiment) atopical composition for the treatment of
rosacea, erythemia, telangiectasia, and inflammatory lesions associated with
rosacea, erythemia, telangiectasia, said topical composition comprising:
a) isopropyl alcohol 99% USP in the amount of about 72.5% - 71.5%
wlw;
b) purified water USP in the amount of about 4.0% w/w;
c) dioctyl maleate MFR in the amount of about 4.85%-5.5% w/w;
d) cyclomethicone NF in the amount of about 2.91%-3.5% w/w;
e) Octyl Methoxycinnamate in the amount of about 7.5%-8.0% w/w;
f) isoarachidyl neopentanoate MFR in the amount of about 3.75%-4.5%
wlw;
g) metronidazole USP in the amount of about 0.50% - 1.50% w/w;
h) Butyl Methoxydibenzoyl methane in the amount of about 2.0%-2.2%
w/w; and
7 2161737
i) hydroxypropyl cellulose NF in the amount of about 1.2%-1.5% w/w, or
pharmaceutically acceptable chemical equivalents of a)-i).
According to yet another aspect of the invention there is provided in
5 one embodiment a composition for the treatment of rosacea and acne comprising: (a) an effective amount of isopropyl alcohol 99% USP
(b) an effective amount of purified water USP
(c) an effective amount of dioctyl maleate MFR
(d) an effective amount of cyclomethicone NF
(e) an effective amount of Octyl Methoxycinnamate
(f) an effective amount of Isoarachidyl neopentanoate MFR
(g) an effective amount of metronidazole USP
(h) an effective amount of Butyl Methoxybenzoyl methane MFR and
(i) an effective amount of hydroxypropyl cellulose NF, or
15 pharmaceutically acceptable equivalents of each of (a) - (i)
According to yet another aspect of the invention there is provided a
method of treating rosacea and acne comprising the topical application of an
effective amount of metronidazole in combination with: an effective amount of at20 least one sunscreen compatible with said metronidazole, preferably selected from
the group consisting of octyl methoxycinnamate and butyl methoxydibenzoyl
methane and a pharmaceutically acceptable vehicle, preferably a substantially
alcoholic base.
According to yet another aspect of the invention there is provided a
method of preparing a pharmaceutical composition for use in treating rosacea,
erythemia, telangiectasia, and inflammatory lesions which method comprises
incorporating an effective non-toxic amount of metronidazole as active ingredient
in the composition together with an effective amount of at least one sunscreen
8 2161737
compatible with said effective non-toxic amount of metronidazole, preferably
selected from the group consisting of octyl methoxy cinnamate and butyl
methoxydibenzoyl methane and preferably in a pharmaceutically acceptable
vehicle, preferably isopropyl alcohol.
According to yet another aspect of the invention there is provided the
use of metronidazole, for the manufacture of a pharmaceutical composition or
compositions for the medical treatment of acne and erythemia, telangiectasia, and
inflammatory lesions associated with rosacea, characterized in that the composition
10 or compositions are for use in humans for the treatment of acne and erythemia,
telangiectasia, and inflammatory lesions, and the composition or compositions
further comprise at least one sunscreen compatible with said metronidazole,
preferably selected from the group consisting of octyl methoxy cinnamate and butyl
methoxydibenzoyl methane and preferably in a pharmaceutically acceptable base
15 for example gel base, preferably using isopropyl alcohol.
According to yet another aspect of the invention there is provided the
use of a non-toxic effective amount of metronidazole in combination with at least
one sunscreen for the treatment of acne and erythemia, telangiectasia and
20 inflammatory lesions associated with rosacea characterized by the use of a
composition which comprises an effective non-toxic amount of metronidazole, an
effective non-toxic amount of sunscreen compatible with said metronidazole and acompatible vehicle.
According to yet another aspect of the invention there is provided a
topical pharmaceutical composition for the treatment of acne and rosacea,
erythemia, telangiectasia, and inflammatory lesions associated with rosacea,
characterized that said composition comprises an effective non-toxic amount of
9 2161737
metronidazole, an effective non-toxic amount of at least one sunscreen compatible
with said metronidazole, where said composition is substantially non-stinging.
According to yet another aspect of the invention there is provided a
5 topical pharmaceutical composition for the treatment of acne and rosacea,
erythemia, telangiectasia, and inflammatory lesions associated with rosacea,
characterized that said composition comprises an effective non-toxic amount of
metronidazole, an effective non-toxic amount of at least one sunscreen compatible
where said composition is substantially preservative free.
In any of the above compositions, it is preferred that said compositions
exhibit substantially at least one of the following characteristics:
(a) substantially non-stinging
(b) substantially non-burning
(c) substantially non-itching
and (d) substantially non-drying.
In any of the above, it is preferred that the sun protection factor (SPF)
20 beatleast15.
The following example is illustrative of the manufacturing process
used to prepare a 1.0% metronidazole gel with sunscreen.
25 Step A
In a suitable stainless steel container equipped with good agitation, charge
1 ) Isopropyl alcohol 99% USP 72.0250 kg
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1 o
2) Purified water USP 4.0 kg
3) Dioctyl maleate MFR 5.0 kg
4) Cyclomethicone NF 3.0 kg
5) Octyl methoxy cinnamate MFR 7.8750 kg
6) Isoarachidyl neopentanoate MFR 4.0 kg
and with stirring, warm to 50~C
Step B
To step A, add and stir until each is completely dissolved.
7) Metronidazole USP 1.0 kg
1 5 then
8) Butylmethoxybenzoylmethane MFR 2.0 kg
Step C
20 Start cooling the batch and in a sprinkling manner during a 5 minute period, add
with good stirring.
9) Hydroxypropyl cellulose NF 1.4 kg
25 Step D
Stir for an additional 10 minutes following the hydroxypropyl cellulose addition,
allow the batch to stand overnight. (preferably >10 hours) and assure the
container is well sealed.
11 21 61 7 37
Step E
Transfer into a holding tank or suitable containers and store in a quarantined area.
5 Label with product name, lot number and quantity.
Step F
Calculate % yield, theoretical and actual, and advise Quality Control for sampling.
10 Compositions having a concentration of metronidazole between 0.50% to 1.50%
w/w were prepared in a similar manner with appropriate adjustments to the amountof Isopropyl alcohol 99% USP. The range being substantially 72.5250% - 71.5250
% w/w equating to 0.50% - 1.50% w/w of metronidazole respectively.
15 The following will provide as illustrative the clinical safety and efficacy of the topical
metronidazole composition prepared according to an embodiment of the invention.
42 patients were initially entered in the study. 30 of them were included in theefficacy analysis for the entire duration of the study. All 42 patients were included
20 in the safety analysis.
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1 2
TABLE I PATIENTS EXCLUDED AT TIME OF WITHDRAWAL OR COMPLETELY
EXCLUDED FROM THE EFFICACY ANALYSIS.
PATIENT # REASON
Completely 1 -Failed to meet inclusion criteria No. 3
excluded from 17 -Withdrawn at Day 3 due to severe stinging
efficacy analysis
34 -Patient on chronic steroid therapy
-Withdrawn at Week 1 due to
unspecified idiosyncratic
papulopustular reaction
39 -Patient on chronic steroid therapy
-Inadequate washout period
Excluded at the 13 -Unable to keep appointment after Week 3
time of withdrawal
or 18 -Withdrawn after Week 9 due to a threatening
protocol violation heart attack
28 -Took a"l b.otics after Week 3
29 -Took antibiotics after Week 3
33 -Patient voluntary withdrawal after Week 3
49 -Took ora H~ ~llun : IE after Week 3
Note: Patient #20 completed the study one week early (Week 1 1 ) to leave
for vacation. This patient was nevertheless fully included in the
efficacy analysis.
10 Study design:
Double-blind, placebo-controlled, randomized, split-face (paired) comparative trial.
Study medication:
1% metronidazole in an alcohol gel with sunscreens made according to
embodiment of the invention.
Placebo: Alcohol gel with sunscreens, (made according to above
20 embodiment of invention without metronidazole).
13 21 61 737
Duration of the study:
The patients were treated for nine weeks. Clinical evaluations were conducted at5 Week 3, 6 and 9. A follow-up evaluation was done at Week 12.
Diagnosis:
All the patients were diagnosed by the investigator as having rosacea. Each
10 patient had a minimum of three papules and/or pustules on each side of the face,
bilateral moderate to severe erythema and bilateral telangiectasia.
Patient demography:
15 Twenty-five women and seventeen men aged between 24 and 71 years
participated in the trial.
Posology:
20 Application of gel occurred twice a day (morning and evening).
Criteria of effectiveness:
The primar,v efficacy variables were the papule and pustule counts and the severity
25 of erythema and telangiectasia. These variables were measured at baseline and at
the end of Weeks 3, 6 and 9 of the treatment. Then, following three weeks off
medication (Week 12), these variables were once more evaluated.
RESULTS:
14 2 i 6 7 ~37
RESULTS:
ASSESSMENT OF EFFICACY
5 Both forms of treatment, particularly the active group, decreased the total number of
inflammatory lesions (papule and pustule). At the end of the treatment (Week 9),the total inflammatory lesion count, compared to baseline, was reduced by 62%
with metronidazole and by 37% with the placebo (Table ll).
10 After three weeks off from the therapy (Week 12), the total number of inflammatory
lesions for both metronidazole and the placebo was still reduced compared to
baseline (Table ll).
TABLE ll GROUP MEAN AND PERCENTAGE DECREASE FROM BASELINE
FOR THE TOTAL INFLAMMATORY LESION COUNT WITH RESPECT
TO TILE AND TREATMENT.
Metronidazole Placebo
Time Mean + SE % Decrease Mean + SE % Decrease
WeekO 8.25 + 0.79 N/A 7.83 + 0.82 33.72
Week 3 5.44 + 0.68 34.06 5.19 + 0.74 33.72
Week6 3.68 + 0.71 55.39 4.61 + 1.11 41.12
Week9 3.16 + 0.94 61.70 4.90 + 1.45 37.42
Week 12 4.30 + 0.92 47.88 5.10 + 1.13 34.87
20 In order to minimize the effect of the variation in the number of inflammatory lesions
at baseline observed among the patients, a statistical analysis was conducted onthe group mean total inflammatory lesion count differences relative to baseline.The results of the statistical analysis, which are presented in Table lll, demonstrate
that both forms of treatment significantly decrease the total papule and pustule25 count and this for all time points of the study.
TABLE lll GROUP MEAN TOTAL PAPULE AND PUSTULE COUNT
DIFFERENCES RELATIVE TO BASELINE AND WITH RESPECT TO
TIME AND TREATMENT.
2 i 6 1 ~3 7
Metronidazole Plac~bo
Time Mean + SE P Value1 Mean +SE P Value1 P Value 2
Week3 2.81 +0.70 0.0003 2.62 +0.69 0.0005 > 0.0
Week6 4.90+0.89 0.0001 3.71 +0.94 0.0004 >0.0
Week9 5.42 + 0.96 0.0001 3.42 + 1.22 0.0086 > 0.0
Week 12 4.43 + 0.87 0.0001 3.33 + 0.94 0.0013 > 0.05
5 1 p value for comparison from baseline within treatment.
2 p value for comparison between treatment.
10 As indicated in Tables Vlll to Xl, the majority of patients did not experience stinging,
burning, itching or dryness. The patients who did experience the above mentionedside effects reported them mostly as mild in nature. These sensations were of short
duration and equally reported for both the placebo and the metronidazole. As thetreatment progressed, the occurrence of these side effects were less frequent and
15 were nearly absent by Week 12.
TABLE Vlll: INCIDENCE OF STINGING AT EACH VISIT
WEEK 3
Absent Mild Moderate Severe
METRONIDAZOLE GEL 22(53.7%) 14(34.2%) 4(9.8%) 1(2.4%)
(n=41)
PLACEBO (n=41) 23(56.1%) 13(31.7%) 4(9.8%) 1(2.4%)
WEEK 6
Absent Mild Moderate Severe
METRONIDAZOLE GEL 27(75.0%) 7(19.4%) 2(5.6%) 0
(n=36)
PLACEBO (n=36) 24(66.7%) 10(27.8%) 2(5.6%) 0
WEEK 9
Absent Mild Moderate Severe
METRONIDAZOLE GEL 25(69.4%) 10(27.8%) 1(2.8%) 0
(n=36)
PLACEBO (n=36) 25(69.4%) 9(25.0%) 2(5.6%) 0
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1 6
WEEK 12 (POSTTREATMENT)
~. i Absent Mild Moderate Severe
METRONIDAZOLE GEL 34(97.1%) 1(2.9%) 0 0
(n=35)
PLACEBO (n=35) 35(100.0%) 0 0 0
TABLE IX: INCIDENCE OF BURNING AT EACH VISIT.
WEEK 3
Absent Mild Moderate Severe
METRONIDAZOLE GEL 30(73.2%) 8(19.5%) 3(7.3%) 0
(n=41)
PLACEBO (n=41) 29(70.7%) 8(19.5%) 3(7.3%) 1(2.4%)
WEEK 6
Absent Mild Moderate Severe
METRONIDAZOLE GEL 26(72.2%) 10(27.8%) 0 0
(n=36)
PLACEBO (n=36) 26(72.2%) 9(25.0%) 1(2.8%) 0
WEEK 9
Absent Mild Moderate Severe
METRONIDAZOLE GEL 30(83.3%) 6(16.7%) 0 0
(n=36)
PLACEBO (n=36) 31(86.1%) 4(11.1%) 1(2.8%) 0
WEEK 12 (POSTTREATMENT)
Absent Mild Moderate Severe
METRONIDAZOLE GEL 35(100.0%) 0 0 0
(n=35)
PLACEBO (n=35) 34(97.1%) 1(2.9%) 0 0
TABLE X: INCIDENCE OF ITCHING AT EACH VISIT.
WEEK 3
Absent Mild Moderate Severe
METRONIDAZOLE GEL 28(68.3%) 10(24.4%) 3(7.3%) 0
(n=41)
PLACEBO (n=41) 28(68.3%) 10(24.4%) 3(7.3%) 0
17 ~'t6!7~7
WEEK 6
~ ~ Absent Mild Moderate Severe
METRONIDAZOLE GEL 28(77.8%) 8(22.2%) 0 0
(n=36)
PLACEBO (n=36) 27(75.0%) 9(25.0%) 0 0
WEEK 9
- ~ Absent Mild Moderate Severe
METRONIDAZOLE GEL 31(86.1%) 5(13.9%) 0 0
(n=36)
PLACEBO (n=36) 30(83.3%) 6(16.7%) 0 0
WEEK 12 (POSTTREATMENT)
~ Absent Mild Moderate Severe
METRONIDAZOLE GEL 34(97.1%) 0 1(2.9%) 0
(n=35)
PLACEBO (n=35) 34(97.1%) 0 1(2.9%) 0
TABLE Xl: INCIDENCE OF DRYNESS AT EACH VISIT.
WEEK 3
Absent Mild Moderate Severe
METRONIDAZOLE GEL 23(56.1%) 10(24.4%) 8(19.5%) 0
(n=41)
PLACEBO (n=41) 20(48.8%) 15(36.6%) 6(14.6%) 0
WEEK 6
Absent Mild Moderate Severe
METRONIDAZOLE GEL 26(72.2%) 8(22.2%) 2(5.6%) 0
(n=36)
PLACEBO (n=36) 26(72.2%) 8(22.2%) 2(5.6%) 0
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1 8
WEEK 9
~ ~ Absent Mild Moderate Severe
METRONIDAZOLE GEL 24(66.7%) 11(30.6%) 1(2.8%) 0
(n=36)
PLACEBO (n=36) 22(61.1 %) 13(36.1 %) 1 (2.8%) 0
WEEK 12 (POSTTREATMENT)
Absent Mild Moderate Severe
METRONIDAZOLE GEL 32)91.4%) 2(5.7%) 1(2.9%) 0
(n=35)
PLACEBO (n=35) 30(85.7%) 4(11.4%) 1 (2.9%) 0
The results showed that, compared to baseline, metronidazole 1 % gel with
sunscreen is effective in significantly decreasing the number of inflammatory
lesions and the level of erythema and telangiectasia associated with rosacea.
15 From the point of safety, most patients did not report side effects.
In conclusion, this study showed evidence of a beneficial effect on the natural
course of rosacea from the topical application of Metronidazole 1% gel.
20 The following provide examples of formulations for metronidazole gel 0.50% w/w
and 1.50% w/w, respectively.
2 ~ 6 1 737
1 9
METRONIDAZOLE GEL 0.5% WITH SUNSCREEN
MANUFACTURING FORMULA FOR 100.0000 kg
.. ~ ~.~ b ~V ~ 5~ 5'~
Isopropyl alcohol 99% USP 72.5250 72.5250
2 Purified Water USP 3.6000 3.6000
3 Dioctyl Maleate MFR 5.0000 5.0000
4 Cyclomethicone NF 3.0000 3.0000
Octylmethoxy cinnamate MFR 7.8750 7.8750
(Parsol MCX MFR + 5% excess)
6 Isoarachidyl neopentanoate MFR 4.0000 4.0000
(Elefac 1-205 MFR)
7 Metronidazole USP 0.5000 0.5000
8 Butylmethoxybenzoyl methane MFR 2.1000 2.1000
(Parsol 1789 MFR + 5 % excess)
9 Hydroxypropyl cellulose NF 1.4000 1.4000
TOTAL 1 00.0000 1 00.000
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.' 20
METRONIDAZOLE GEL 1.5% WITH SUNSCREEN
MANUFACTURING FORMULA FOR 100.0000 kg
Isopropyl alcohol 99% USP 71.5250 71.5250
2 Purified Water USP 3.6000 3.6000
3 Dioctyl Maleate MFR 5.0000 5.0000
4 Cyclomethicone NF 3.0000 3.0000
Octylmethoxy cinnamate MFR 7.8750 7.8750
(Parsol MCX MFR + 5% excess)
6 Isoarachidyl neopentanoate MFR 4.0000 4.0000
(Elefac 1-205 MFR)
7 Metronidazole USP 1.5000 1.5000
8 Butylmethoxybenzoyl methane MFR 2.1000 2.1000
(Parsol 1789 MFR + 5 % excess)
9 Hydroxypropyl cellulose NF 1.4000 1.4000
TOTAL 1 00.0000 1 00.000
5 Although Parsols were described in the preferred embodiment of the inventions as
the sunscreens, other compatible sunscreens can be used. Parsols are preferred
due to their substantially non-sensitizing characteristics as opposed to PABA and
it's ester derivatives that have been demonstrated to cause contact and photo
contact sensitization in treated subjects.
10 As many changes can be made to the examples and embodiments described
herein without departing from the scope of the invention, it is intended that all
material contained herein be interpreted as illustrative of the invention and not in a
limiting sense.
