U.S. patent application number 16/789724 was filed with the patent office on 2020-06-11 for dermatological compositions and methods.
The applicant listed for this patent is Sandoz, Inc.. Invention is credited to Kenneth L. Evenstad, Victoria A. O'Neill, Gloria A. Rood.
Application Number | 20200179405 16/789724 |
Document ID | / |
Family ID | 23136236 |
Filed Date | 2020-06-11 |
United States Patent
Application |
20200179405 |
Kind Code |
A1 |
Rood; Gloria A. ; et
al. |
June 11, 2020 |
DERMATOLOGICAL COMPOSITIONS AND METHODS
Abstract
Dermatological compositions (methods of making and using) that
include one or more anesthetic agents and/or one or more
anti-inflammatory agents and/or a combination of ammonium, sodium,
and potassium salts, preferably of an alpha-hydroxy acid.
Inventors: |
Rood; Gloria A.; (Maple
Grove, MN) ; Evenstad; Kenneth L.; (Wayzata, MN)
; O'Neill; Victoria A.; (Wayzata, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Sandoz, Inc. |
Princeton |
NJ |
US |
|
|
Family ID: |
23136236 |
Appl. No.: |
16/789724 |
Filed: |
February 13, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15914039 |
Mar 7, 2018 |
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16789724 |
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15283593 |
Oct 3, 2016 |
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15914039 |
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14851203 |
Sep 11, 2015 |
9456970 |
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15283593 |
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13198928 |
Aug 5, 2011 |
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14851203 |
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12479524 |
Jun 5, 2009 |
8013017 |
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13198928 |
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10977374 |
Oct 29, 2004 |
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12479524 |
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10159562 |
May 31, 2002 |
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10977374 |
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60295105 |
May 31, 2001 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 31/56 20130101; A61K 2800/524 20130101; A61Q 19/007
20130101; A61K 47/44 20130101; A61K 31/5375 20130101; A61Q 19/00
20130101; A61K 31/573 20130101; A61K 8/31 20130101; A61K 31/535
20130101; A61K 31/573 20130101; A61K 45/06 20130101; A61K 31/535
20130101; A61P 17/08 20180101; A61K 8/345 20130101; A61K 9/0014
20130101; A61K 31/19 20130101; A61K 8/73 20130101; A61K 8/368
20130101; A61P 29/00 20180101; A61K 8/49 20130101; A61P 23/00
20180101; A61K 8/365 20130101; A61K 31/56 20130101; A61P 17/00
20180101; A61K 8/361 20130101; A61K 31/19 20130101 |
International
Class: |
A61K 31/573 20060101
A61K031/573; A61Q 19/00 20060101 A61Q019/00; A61K 31/5375 20060101
A61K031/5375; A61K 8/73 20060101 A61K008/73; A61K 8/368 20060101
A61K008/368; A61K 8/36 20060101 A61K008/36; A61K 8/34 20060101
A61K008/34; A61K 8/31 20060101 A61K008/31; A61K 8/365 20060101
A61K008/365; A61K 47/44 20060101 A61K047/44; A61K 45/06 20060101
A61K045/06; A61K 31/56 20060101 A61K031/56; A61K 31/535 20060101
A61K031/535; A61K 31/19 20060101 A61K031/19; A61K 9/00 20060101
A61K009/00; A61K 8/49 20060101 A61K008/49 |
Claims
1. A dermatological composition comprising: about 8 weight percent
to about 40 weight percent of deodorized ammonium lactate; about 1
weight percent to about 20 weight percent of mineral oil; about 0.5
weight percent to about 3 weight percent of dimethylsiloxane
polymers. a nonionic surfactant; a preservative; about 1 weight
percent to about 10 weight percent of glycerin; about 0.0001 weight
percent to about 10 weight percent of xanthan gum; stearyl alcohol;
about 30% and typically no greater than about 60% by weight of
water; wherein the composition has a pH of about 4.5 to about
5.5.
2. The dermatological composition of claim 1 wherein: the
deodorized ammonium lactate is present in the composition in an
amount of about 19.7 weight percent; the mineral oil is present in
the composition in an amount of about 10 weight percent; the
dimethylsiloxane polymers are present in the composition in an
amount of about 2 weight percent; the glycerin is present in the
composition in an amount of about 4 weight percent; the xanthan gum
is present in the composition in an amount of about 0.2 weight
percent; and the nonionic surfactant comprises glyceryl
stearate.
3. A dermatological composition comprising: about 10 weight percent
to about 15 weight percent of ammonium lactate; about 3 weight
percent to about 7 weight percent of sodium lactate; about 3 weight
percent to about 7 weight percent of potassium lactate; about 1
weight percent to about 20 weight percent of mineral oil; about 0.5
weight percent to about 3 weight percent of dimethylsiloxane
polymers. a nonionic surfactant; a preservative; petrolatum; about
1 weight percent to about 10 weight percent of glycerin; about
0.0001 weight percent to about 10 weight percent of xanthan gum;
stearyl alcohol; about 30% and typically no greater than about 60%
by weight of water; wherein the composition has a pH of about 4.5
to about 5.5.
4. The dermatological composition of claim 3 wherein: the ammonium
lactate is present in the composition in an amount of about 10.5
weight percent; the sodium lactate is present in the composition in
an amount of about 4.2 weight percent; the potassium lactate is
present in the composition in an amount of about 4.2 weight
percent; the mineral oil is present in the composition in an amount
of about 4 weight percent; the dimethylsiloxane polymers are
present in the composition in an amount of about 2 weight percent;
the glycerin is present in the composition in an amount of about 5
weight percent; the xanthan gum is present in the composition in an
amount of about 0.3 weight percent; and the nonionic surfactant
comprises glyceryl stearate.
5. A method of treating skin of a subject, the method comprising
contacting the subject's skin with a dermatologic composition of
claim 1.
6. A method of treating skin of a subject, the method comprising
contacting the subject's skin with a dermatologic composition of
claim 2.
7. A method of treating skin of a subject, the method comprising
contacting the subject's skin with a dermatologic composition of
claim 3.
8. A method of treating skin of a subject, the method comprising
contacting the subject's skin with a dermatologic composition of
claim 4.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation application of Ser. No.
15/283,593, filed on Oct. 3, 2016, which is a continuation
application of Ser. No. 14/851,203, filed Sep. 11, 2015, now U.S.
Pat. No. 9,456,970, which is a continuation application of Ser. No.
13/198,928, filed on Aug. 5, 2011, now abandoned, which is a
continuation application of Ser. No. 12/479,524, filed on Jun. 5,
2009, now U.S. Pat. No. 8,013,017, which is a continuation
application of Ser. No. 10/977,374, filed on Oct. 29, 2004, now
abandoned, which is a divisional application of Ser. No.
10/159,562, filed on May 31, 2002, now abandoned, which claims the
benefit of U.S. Provisional Application Ser. No. 60/295,105 filed
May 31, 2001, each of which is incorporated by reference, in their
entirety.
FIELD OF THE INVENTION
[0002] The invention relates to topical compositions that provide
dermatological benefit, such as for the treatment of inflammation,
itching, pain relief, and/or other conditions associated with skin
disorders.
BACKGROUND OF THE INVENTION
[0003] Severe dry skin disorders, known as ichthyosis, are often
characterized by cracks, flakes, scales, redness, etc. Less severe,
but more common, moderate to mild dry skin disorders are often
characterized by less severe fissures, chaps, cracks, flakes,
redness, etc. Such disorders can also include inflammation and be
quite painful. Typically, such disorders are treated with topical
oils, hydrating emollients, ointments, etc.
[0004] The topical use of alpha-hydroxy and beta-hydroxy acids,
alpha-ketoacids, and esters thereof, is well known in the art to be
effective as a preventative as well as a therapeutic treatment of
dry skin disorders. Treatment is generally effective at acid
concentrations of about 1% to about 20% by weight. Skin irritation
caused by low pH levels may be ameliorated by neutralizing the
acids with a base, such as ammonium hydroxide. See, for example,
U.S. Pat. No. 4,105,783 (Yu et al.).
[0005] Further, it is believed that skin penetration by such
compositions is enhanced using acid/base salts. See, for example,
U.S. Pat. No. 4,888,354 (Chang et al.). In addition, the topical
compositions may contain additional pharmaceutical and cosmetic
additives, provided they do not adversely affect the formulation,
stability, and activity of the acids and/or esters. Such additives
include, for example, antimicrobials, antibiotics, neoplastic
agents, cardiac drugs, antihistamines, anesthetics, antipsychotics,
etc. See, for example, U.S. Pat. No. 4,888,354 (Chang et al.), U.S.
Pat. No. 5,420,106 (Parab), and U.S. Pat. No. 5,705,168
(Parab).
[0006] There is still a need for compositions (e.g., lotions and
creams) that can be used to reduce conditions associated with dry
skin and other skin disorders, such as inflammation, itching,
and/or pain relief.
SUMMARY OF THE INVENTION
[0007] One aspect of the present invention combines
dermatologically acceptable compositions (i.e., dermatological or
dermatologic compositions) with one or more anesthetic and/or
anti-inflammatory agents, preferably steroid anti-inflammatory
agents. The compositions include at least one acid, amide, ester,
or salt of an alpha-hydroxy acid, a beta-hydroxy acid, an
alpha-keto acid, or combinations thereof (preferably at least one
alpha-hydroxy acid, ester, amide, salt thereof, or combinations
thereof). More preferably, the compositions include a combination
of at least two salts, more preferably, at least one ammonium salt
and at least one metal ion salt (preferably sodium or potassium
salt) for enhanced penetration of the composition. Preferably,
certain compositions include an anti-foaming agent.
[0008] A further aspect of the present invention is a composition
including at least one alpha hydroxy acid, at least one ammonium
salt of an alpha hydroxy acid, at least one potassium salt of an
alpha hydroxy acid, and at least one sodium salt of an alpha
hydroxy acid.
[0009] These compositions can also optionally include topical
vehicles such as non-ionic surfactants, thickeners, emollients,
humectants, and preservatives to provide preparations, such as
lotions, creams, etc., for dry skin having enhanced preventative
and therapeutic attributes.
[0010] The present invention provides methods for treating a
subject, preferably a mammal, and more preferably a human, such as
reducing inflammation of the skin, reducing itching and/or pain of
the skin, and treating skin disorders that include contacting the
skin with compounds containing any of the compositions of the
present invention.
[0011] Another aspect of the present invention provides methods for
preparing the dermatological compositions that include combining at
least one acid, amide, ester, or salt of an alpha-hydroxy acid,
beta-hydroxy acid, alpha-keto acid, or combinations thereof
(preferably at least one alpha-hydroxy acid, ester, amide, salt
thereof, or combinations thereof), with one or more anesthetic
agents and/or one or more anti-inflammatory agents. Preferably,
such methods also include adding one or more ammonium salts and/or
one or more metal ion salts. A preferred method of preparing
certain dermatological compositions of the present invention
includes providing an alpha-hydroxy acid and neutralizing at least
a portion of it with ammonium hydroxide in an aqueous solution to
provide a neutralized acid solution that preferably may be combined
with at least one anti-inflammatory agent and/or at least one
anesthetic agent.
[0012] A further method of preparing a dermatologic composition of
the present invention includes combining at least one alpha-hydroxy
acid, beta-hydroxy acid, or alpha-keto acid, or combinations
thereof, with at least one ammonium salt of an alpha-hydroxy acid,
beta-hydroxy add, or alpha-keto acid, or combinations thereof, at
least one sodium salt of an alpha hydroxy acid, beta-hydroxy acid,
or alpha-keto acid, or combinations thereof, and at least one
potassium salt of an alpha hydroxy acid, beta-hydroxy acid, or
alpha-keto acid, or combinations thereof. Preferably, the method
includes combining at least one alpha-hydroxy acid, beta-hydroxy
acid, or alpha-keto acid, or combinations thereof, with at least
two of the above ammonium, sodium, and potassium salts.
[0013] High concentrations, such as from about 10% to about 30% by
weight, of alpha-hydroxy acids in a skin preparation, when
neutralized to yield the ammonium salts, have been found to develop
an unpleasant odor and occasionally may result in yellow coloration
over time. Thus, the present invention also provides a method for
preparing such compositions using activated charcoal for
deodorizing. Compositions of the invention may be contacted with
activated charcoal. Thereafter, the charcoal may be separated from
the composition. Compositions that may be contacted with the
activated charcoal may include compositions that have been
neutralized with ammonium hydroxide. Deodorizing is defined as
removing or significantly reducing a fragrance by neutralization or
adsorption. Odor-free is defined as a fragrance completely or
substantially eliminated from a composition.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
[0014] The invention concerns dermatological compositions that can
be in the form of dermatologically acceptable lotions and creams,
for example. The compositions of the present invention can be used
to treat one or more skin disorders, such as dry skin, ichthyosis,
inflammation, and irritation. Certain preferred compositions can be
used to reduce the amount of inflammation of the skin of a human.
Certain other preferred compositions can be used to reduce the
amount of itching and/or pain of the skin of a human. Certain other
preferred compositions include a combinations of salts that enhance
skin penetration of the active ingredients of the compositions.
[0015] Acids, Amides, Esters, Salts
[0016] The dermatological compositions include at least one active
ingredient selected from an acid, amide, ester, or salt.
Preferably, such active ingredients are racemic mixtures and,
preferably, are selected from the group of an alpha-hydroxy acid, a
beta-hydroxy acid, an alpha-keto acid, an ester thereof, an amide
thereof, a salt thereof, and combinations thereof. More preferably,
such active ingredients are selected from the group of an
alpha-hydroxy acid, an amide thereof, an ester thereof, a salt
thereof, and combinations thereof. Certain preferred embodiments
include a combination of at least one alpha-hydroxy acid and at
least one salt thereof. Preferably the salt is an ammonium salt, a
metal ion salt (e.g., a potassium salt or a sodium salt), or a
combination thereof. More preferably, a combination of such salts
is used. Even more preferably, at least two different salts are
used. Most preferably, a combination of an ammonium salt, a
potassium salt, and a sodium salt is used.
[0017] Examples of such acids, amides, esters, or salts include
citric acid, glycolic acid, glucuronic acid, galacturonic acid,
alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid,
beta-hydroxybutyric acid, lactic acid, malic acid, mandelic acid,
mucic acid, pyruvic acid, saccharic acid, tartaric acid, tartronic
acid, maleic acid, beta-phenyllactic acid, beta-phenylpyruvic acid,
glucuronolactone, gluconolactone, methyl pyruvate, ethyl pyruvate,
salts thereof, and combinations thereof.
[0018] A preferred set of such active ingredients includes the
alpha-hydroxy acids. Alpha-hydroxy acids are aliphatic mono- and
di-carboxylic acids including, but not limited to, citric acid,
glycolic acid, glucuronic acid, galacturonic acid,
alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid, lactic
acid, malic acid, mandelic acid, mucic acid, pyruvic acid,
saccharic acid, tartaric acid, tartonic acid, and the like.
Preferred alpha-hydroxy acids of the present invention are those of
the formula (I): R--CH(OH)--COOH, wherein R is an alkyl group or a
hydrogen. Preferably, R is a C.sub.1 to C.sub.5 alkyl group
including, for example, methyl, ethyl, propyl, butyl, or pentyl as
well as branched groups thereof. Preferred acids include lactic,
glycolic, and malic acids. Most preferred is lactic acid.
[0019] Typically, the compositions include both an acid and a salt
thereof, as for example, an alpha-hydroxy acid and an ammonium salt
thereof. The alpha-hydroxy acids and a base, such as ammonium
hydroxide, are typically reacted in an aqueous solution to provide
a neutralized acid solution. Generally, at least a portion of the
acid is neutralized. Thus, as used herein, a "neutralized" acid
solution or combination of acids in solution is defined as an acid
solution in which at least a portion of the acid is neutralized to
provide the salt of the acid or acids. The neutralized acid
solution, formed when an acid is reacted with an
ammonium-containing base, such as ammonium hydroxide, can be
generally free of unreacted ammonia (herein "unreacted ammonia"
refers to dissolved ammonium ions). This may occur when a
stoichiometrically lesser amount of the base is added to the acid.
A neutralized acid solution, as defined herein, may also include
solutions in which unreacted ammonia is present.
[0020] The compositions preferably include one or more acids,
amides, esters, or salts present in a total amount (e.g., acid plus
salt) of at least about 1% by weight, more preferably at least
about 5% by weight, and even more preferably at least about 8% by
weight, based on the total weight of the composition (e.g., lotion,
cream, etc.). Additionally, the one or more acids, amides, esters,
or salts are present in the compositions in a total amount no
greater than about 50% by weight, more preferably, no greater than
about to about 40% by weight, and even more preferably no greater
than about 15%, based on the total weight of the composition.
Typically, one or more acids, in the form of a free acid, in
combination with one or more salts are present in the compositions.
Preferably, the total amount of one or more free acids is at least
about 1% by weight, and more preferably, at least about 10% by
weight, based on the total weight of the composition. Preferably,
the total amount of one or more free acids is no greater than about
30% by weight, more preferably, no greater than about 20% by
weight, and most preferably no greater than about 15% by weight,
based on the total weight of the composition. Preferably, the total
amount of one or more salts is at least about 1% by weight, and
more preferably, at least about 5% by weight, based on the total
weight of the composition. Preferably, the total amount of one or
more salts is no greater than about 40% by weight, and more
preferably, no greater than about 30% by weight, based on the total
weight of the composition. The pH of the compositions of the
present invention are preferably at least about 3, and more
preferably at least about 4.5, and preferably no greater than about
6, and more preferably no greater than about 5.5.
[0021] In certain preferred embodiments, the compositions include a
combination of one or more ammonium salts, one or more potassium
salts, and one or more sodium salts. Even more preferably, the
compositions include a combination of 2 or more salts. In such
compositions, preferably, the total amount of ammonium salts, if
present, (preferably, of one or more alpha-hydroxy acids) is at
least about 1% by weight, and more preferably, at least about 5% by
weight, based on the total weight of the composition. Preferably,
the total amount of ammonium salts, if present, (preferably, of one
or more alpha-hydroxy acids) is no greater than about 40% by
weight, and more preferably, no greater than about 30% by weight,
based on the total weight of the composition. Most preferably, the
ammonium salt is ammonium lactate and, if present, is present in an
amount of, preferably at least about 10% and more preferably at
least about 15.9%, and preferably no greater than about 29.6%, even
more preferably no greater than about 15%, based on the total
weight of the composition. In such compositions, preferably, the
total amount of potassium salts, if present, (preferably, of one or
more alpha-hydroxy acids) is at least about 1% by weight, and more
preferably, at least about 5% by weight, based on the total weight
of the composition. Preferably, the total amount of potassium
salts, if present, (preferably, of one or more alpha-hydroxy acids)
is no greater than about 30% by weight, and more preferably, no
greater than about 20% by weight, based on the total weight of the
composition. Most preferably, the potassium salt is potassium
lactate and, if present, is present in an amount of at least about
3% and no greater than about 7%, based on the total weight of the
composition. In such compositions, preferably, the total amount of
sodium salts, if present, (preferably, of one or more alpha-hydroxy
acids) is at least about 1% by weight, and more preferably, at
least about 5% by weight, based on the total weight of the
composition. Preferably, the total amount of sodium salts, if
present, (preferably, of one or more alpha-hydroxy acids) is no
greater than about 30% by weight, and more preferably, no greater
than about 20% by weight, based on the total weight of the
composition. Most preferably, the sodium salt is preferably sodium
lactate and, if present, is present in an amount of about 3% and no
greater than about 7%, based an the total weight of the
composition.
[0022] Anesthetic Agents and/or Anti-Inflammatory Agents
[0023] Certain preferred compositions may additionally include one
or more anesthetic agents and/or anti-inflammatory agents to
provide enhanced therapeutic benefits to the skin preparation.
Typically, an anti-inflammatory agent will reduce, and preferably,
eliminate, inflammation of the skin of a subject when the
composition is applied topically. Typically, an anesthetic agent
will reduce, and preferably, eliminate, itching and/or pain of the
skin of a subject when the composition is applied topically.
Various combinations of such agents can be used for desired
effect.
[0024] Anesthetic agents that can be used in the present invention
include topical local anesthetics, such as anesthetics that can be
used topically on the skin or can be injected as a local
anesthetic. Examples of such topical local anesthetic agents
include, but are not limited to, pramoxine HCl, benzocaine, benzyl
alcohol, dibucaine HCl, dyclonine HCl, lidocaine, tetracaine, and
tetracaine HCl. Combinations of such agents can be used. A
preferred anesthetic agent is pramoxine HCl.
[0025] Preferably, the total amount of one or more anesthetic
agents, if present, is at least about 0.5% and more preferably at
least about 0.75%, based on the total weight of the composition.
Preferably, the total amount of one or more anesthetic agent is no
greater than about 20%, and more preferably, no greater than about
5%, based on the total weight of the composition.
[0026] Anti-inflammatory agents that can be used in the present
invention include steroids (i.e., corticosteroids). Examples of
such agents include, but are not limited to, hydrocortisone
acetate, betamethasone dipropionate, amcinonide, betamethasone
valerate, fluocinolone acetonide, triamcinolone acetonide,
clocortolone pivalate, and dexamethasone. Combinations of such
agents can be used. A preferred steroid for use in the present
invention is hydrocortisone acetate.
[0027] Preferably, the total amount of one or more
anti-inflammatory agents, if present, is at least about 0.01%, and
more preferably, at least about 0.05% by weight, based on the total
weight of the composition. Preferably, the total amount of one or
more anti-inflammatory agent is no greater than about 2.5%, and
more preferably, no greater than about 1.5% by weight, based on the
total weight of the composition.
[0028] Anti-Foaming Agents
[0029] Anti-foaming agents, or foam depressants, are optionally
added to the compositions of the present invention to prevent
undesirable creaming upon application of the composition when
rubbed into the skin. "Creaming" is understood by those skilled in
the art to occur when a composition rubbed into the skin forms a
white layer on the skin before penetration. The more vigorously the
composition is rubbed, the whiter the composition becomes. It has
been discovered that by adding an anti-foaming agent to a
dermatological composition, creaming is substantially eliminated.
Although not caused exclusively by anesthetic agents, creaming may
occur when one or more topical anesthetic agents, particularly
pramoxine HCl, is present in the composition. Pramoxine HCl is a
desirable anesthetic agent as compared with other anesthetics, such
as lidocaine and benzocaine, because many people have allergies to
these other anesthetics. Pramoxine HCl does not cause the same
topical sensitivity as compared to these other anesthetics, it is
effective at minimal concentrations, and has a duration of action
longer than that of other anesthetics (see, for example, Fisher, A.
F.; "The Safety of Pramoxine Hydrochloride When Used as a Topical
(Surface) Anesthetic," Cutis, 62:122-123 (1998); Fisher, A. A.;
"Allergic Reactions to Topical (Surface) Anesthetics with Reference
to the Safety of Tronothane," Cutis, 25:584 (1980); and Schmidt, J.
L., Blockus, L. E., Richards, R. K., "The Pharmacology of Pramoxine
Hydrochloride: A New Topical Anesthetic," Anesth. Analg., 32:418
(1953)), but it does have the undesirable side-effect of causing
creaming upon application to the skin when used in the compositions
of the present invention. This problem is solved by including an
anti-foaming agent in the compositions of the present
invention.
[0030] Acceptable anti-foaming agents of the present invention
include silicone-based oils, preferably dimethylsiloxane polymers,
and copolyol waxes. Such dimethylsiloxane polymers are commercially
available under the trade designations DIMETHICONE 250, DIMETHICONE
350, DIMETHICONE 450, CYCLOMETHICONE, and DIMETHICONE, all from Dow
Corning, Midland, Mich. A particularly preferred anti-foaming agent
is DIMETHICONE 350 dimethylsiloxane polymer. Combinations of such
agents can be used. Effective concentrations of DIMETHICONE 350
from Dow Corning, Midland, Mich., or other anti-foaming agents in
the compositions of the present invention, if present, are at least
about 0.25% by weight, more preferably at least about 0.5% by
weight, and most preferably at least about 0.8% by weight.
Preferably, the compositions include no greater than about 3% by
weight, more preferably no greater than about 2% by weight, and
most preferably no greater than about to about 1.2% by weight.
[0031] Non-Ionic Surfactants
[0032] Non-ionic surfactants are present in preferred formulations
to aid in providing an emulsion of the composition. Selection of
surfactant and concentration of the surfactant will have a
significant effect on the overall "feel" of the composition. Also,
a greater stability of the composition may be gained through the
blending of multiple non-ionic surfactants than may be achieved
through the use of any single surfactant. Preferred non-ionic
surfactants that may be used in the compositions of the present
invention include glyceryl stearate, PEG 100-stearate,
polyoxyl-20-cetostearyl ether, glyceryl monooleate, glyceryl
palmitostearate, self-emulsifying wax, polyoxyl-20-stearate,
polyoxyl-40-stearate, polyoxyl-60-stearate, polyoxyl-80-stearate,
polyoxyl-20-oleate, polyoxyl-40-oleate, polyoxyl-60-oleate,
polyoxyl-80-oleate, polyoxyl-20-palmitate, polyoxyl-40-palmitate,
polyoxyl-60-palmitate, polyoxyl-80-palmitate, laureth-2, laureth-4,
laureth-6, and laureth-8. More preferred non-ionic surfactants
include emulsifying wax, such as POLAWAX (available from Croda,
Parsippany, N.J.), laureth-4, and polyoxyl-40-stearate. A most
preferred non-ionic surfactant is self-emulsifying wax.
[0033] Combinations of such agents can be used such as a
combination is glyceryl stearate and PEG-100 stearate. A preferred
non-ionic surfactant of the present invention includes a system of
glyceryl stearate, PEG-100 stearate, polyoxyl-40-stearate, and
laureth-4. Glyceryl stearate and PEG-100 stearate are supplied
pre-blended by Uniqema (formerly ICI Americas, New Castle, Del.).
Effective concentrations of the pre-blended glyceryl stearate and
PEG-100 stearate in the compositions of the present invention are
at least about 2.0% by weight, and more preferably at least about
2.75% by weight, based on the total weight of the composition.
Preferably, compositions of the present invention contain no
greater than about 5.5% by weight, and more preferably no greater
than about to about 5.25% by weight, based on the total weight of
the composition. Polyoxyl-40-stearate is selected because the
stearates tend to enhance composition stability in comparison to
the oleates and palmitates. Polyoxyl-40-stearate is available in
cosmetic grade from Uniqema (New Castle, Del.). Effective
concentrations of polyoxyl-40-stearate in the compositions of the
present invention are preferably at least about 0.5% by weight, and
more preferably at least about 0.75% by weight, based on total
weight of the composition. Preferably, effective concentrations of
polyoxyl-40-stearate in the compositions of the present invention
are no greater than about 5% by weight, and more preferably no
greater than about 1.25% by weight, based on total weight of the
composition. Effective concentrations of laureth-4 in the
compositions of the present invention are preferably at least about
0.5% by weight, and more preferably at least about 1.25% by weight,
based on total weight of the composition. Effective concentrations
of laureth-4 in the compositions of the present invention are
preferably no greater than about 3%, and more preferably no greater
than about 1.75% by weight, based on total weight of the
composition. Effective concentrations of emulsifying wax in
preferred compositions of the present invention are preferably at
least about 2% and preferably no greater than about 10%, based on
the total weight of the composition.
[0034] Thickeners
[0035] Although the non-ionic surfactants impart a certain amount
of thickening to the compositions of the present invention, it is
difficult to find the correct balance of surfactants and
concentrations thereof that will impart the desired stability to
the composition. Therefore, thickeners, also known in the art as
viscosity modifiers, are preferably used to adjust the composition
to the desired consistency without affecting the stability imparted
by the non-ionic surfactant system. Acceptable thickeners that may
be used in the compositions of the present invention include methyl
cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, cetyl
alcohol, cetostearyl alcohol, stearyl alcohol, magnesium aluminum
silicate, xanthan gum, aluminum magnesium silicate, tribeneonite,
kaolin, magnesium trisilicate, monemorillonite, saeonite, stearic
acid, and talc. Combinations of such agents can be used.
[0036] A preferable thickener of the present invention includes a
system of methyl cellulose, cetyl alcohol, and magnesium aluminum
silicate. Magnesium aluminum silicate is particularly preferred
element of the thickener system as it acts as both an emulsion
stabilizer as well as a viscosity modifier. It also imparts to the
composition a smooth, silky, slippery feel without affecting the
stability of the composition contributed by the non-ionic
surfactant system and does not interfere with the creaming
prevention of the anti-foaming agent. Effective concentrations of
methyl cellulose in the compositions of the present invention are
preferably at least about 0.0001% by weight, and more preferably at
least about 0.0005% by weight, based on total weight of the
composition. Effective concentrations of methyl cellulose in the
compositions of the present invention are preferably no greater
than about 1% by weight, and more preferably no greater than about
0.5% by weight, based on total weight of the composition. Effective
concentrations of cetyl alcohol in the compositions of the present
invention are preferably at least about 0.2% by weight, and more
preferably at least about 0.5% by weight, based on total weight of
the composition. Effective concentrations of cetyl alcohol in the
compositions of the present invention are preferably no greater
than about 5% by weight, and more preferably no greater than about
3.25% by weight, based on total weight of the composition.
Effective concentrations of magnesium aluminum silicate in the
compositions of the present invention are preferably at least about
0.5% by weight, more preferably at least about 1% by weight, and
most preferably at least about 1.25% by weight, based on total
weight of the composition. Effective concentrations of magnesium
aluminum silicate in the compositions of the present invention are
preferably no greater than about 10% by weight, more preferably no
greater than about 5% by weight, and most preferably no greater
than about 1.75% by weight, based on total weight of the
composition.
[0037] An additional preferred thickener of compositions of the
present invention includes stearic acid. In these preferred
compositions thickened using stearic acid, the stearic acid is
preferably present in an amount of at least about 1% and no greater
than about 5%, based on total weight of the composition.
[0038] Emollients and Humectants
[0039] Emollients and humectants soften the skin and stabilize and
control the moisture content of a dermatological composition.
Preferred emollients that may be used in the compositions of the
present invention include glycerin 99.5%, glycerin 95%, glycerin
85%, cetyl alcohol, light mineral oil, medium mineral oil, and
heavy mineral oil. Preferred humectants that may be used in the
compositions of the present invention include glycerin 99.5%,
glycerin 95%, glycerin 85%, propylene glycol, and butylene glycol.
Combinations of such agents can be used.
[0040] More preferable emollients and humectants of the present
invention include glycerin 99.5%, propylene glycol, and light
mineral oil. Glycerin 99.5% and propylene glycol, when used
together, typically act synergistically to aid in stabilizing
compositions of the present invention. Further, propylene glycol
enhances penetration of the skin by compositions at concentrations
of 5% by weight or more, based on total weight of the composition.
Conversely, butylene glycol used alone is not a penetration
enhancer, but does work synergistically with glycerin 99.5% to
enhance penetration. Effective concentrations of glycerin 99.5% in
the compositions of the present invention are preferably at least
about 1% by weight, more preferably at least about 3% by weight,
and even more preferably at least about 3.75% by weight, based on
total weight of the composition. Effective concentrations of
glycerin 99.5% in the compositions of the present invention are
preferably no greater than about 10% by weight, more preferably no
greater than about 6% by weight, and even more preferably no
greater than about 4.25% by weight, based on total weight of the
composition. Effective concentrations of propylene glycol in the
compositions of the present invention are preferably at least about
1% by weight, and more preferably at least about 3% by weight,
based on total weight of the composition. Effective concentrations
of propylene glycol in the compositions of the present invention
are preferably no greater than about 15% by weight, and more
preferably no greater than about 10% by weight, based on total
weight of the composition.
[0041] Light mineral oil is preferable as an emollient as it
imparts less of a greasy feel to the composition, giving it a
lighter feel than do the heavier oils. Effective concentrations of
light mineral oil in the compositions of the present invention are
preferably at least about 1% by weight, more preferably at least
about 3% by weight, even more preferably at least about 4% by
weight, and most preferably at least about 5% by weight, based on
total weight of the composition. Effective concentrations of light
mineral oil in the compositions of the present invention are
preferably no greater than about 20% by weight, more preferably no
greater than about 15% by weight, and most preferably no greater
than about 12% by weight, based on total weight of the
composition.
[0042] Preservatives
[0043] Preservatives prolong the useful life of the composition by
killing bacteria, yeasts, and molds which may impair the
effectiveness of the compositions of the present invention.
Preferable preservatives that may be used in the compositions of
the present invention include methylparaben, ethylparaben,
propylparaben, propylparaben potassium salt, propylparaben sodium
salt, and butylparaben. Combinations of such agents can be used.
More preferable preservatives of the present invention include
methylparaben and propylparaben. Methyl and propylparaben attack
water-bourne microbes, and when used together, their effectiveness
is greater than each used alone. Effective concentrations of
methylparaben in the compositions of the present invention are
preferably at least about 0.02% by weight, and more preferably at
least about 0.1% by weight, based on total weight of the
composition. Effective concentrations of methylparaben in the
compositions of the present invention are preferably no greater
than about 1% by weight, more preferably no more than about 0.3% by
weight, and even more preferably no greater than about 0.2% by
weight, based on total weight of the composition. Effective
concentrations of propylparaben in the compositions of the present
invention are preferably at least about 0.01% by weight, more
preferably at least about 0.025% by weight, and even more
preferably at least about 0.1%, based on total weight of the
composition. Effective concentrations of propylparaben in the
compositions of the present invention are preferably no greater
than about 1% by weight, more preferably no greater than about 0.6%
by weight, and even more preferably no greater than about 0.075% by
weight, based on total weight of the composition.
[0044] Fragrance
[0045] If desired, a component may be added to the composition to
impart a fragrance. Fragrances may be used to add a pleasing scent
to a generally unscented composition or, alternatively, may be used
to assist in concealing the odor of a composition having a strong
and/or unpleasant scent. Fragrance components, if included in a
preferred composition, are preferably present in the compositions
in an amount of no greater than about 1% by weight, based on the
total weight of the composition.
[0046] Water, preferably purified water, is typically and
preferably used in the compositions of the invention. Water may be
used in any amount required to prepare the compositions of the
invention, but is typically present in an amount of at least about
30% and typically no greater than about 60% by weight, based on the
total weight of the composition.
[0047] Methods of Preparation
[0048] An acid/acid salt solution is made by mixing a selected
alpha-hydroxy, beta-hydroxy, alpha-keto acid, an ester, amide, or
salt thereof, an ammonium salt, a metal ion salt, or a combination
of any of the above, with purified water or by neutralizing an acid
with a stoichiometrically lesser amount of base, such as ammonium
hydroxide, to form the "neutralized" acid/acid salt solution.
Alternatively, a commercially available salt, such as an ammonium
lactate solution (available from PURAC America, Lincolnshire, Ill.,
or Pfanstiehl Labs, Inc., Waukegan, Ill.) may be combined with an
acid to form an acid/acid salt solution.
[0049] A Gum Phase composition is preferably prepared by mixing a
thickener and, optionally, fillers, into hot, purified water,
mixing until uniform at a temperature of about 80.degree. C. to
about 85.degree. C. A Water Phase composition is preferably
prepared using hot purified water, optionally including
emulsifiers, humectants, lubricants, thickeners, and antimicrobial
agents. The Gum Phase is typically transferred to the Water Phase
and mixed, maintaining a temperature of about 80.degree. C. to
about 85.degree. C. An Oil Phase composition is preferably prepared
by mixing mineral oil with, optionally, one or more of a
surfactant, a lubricant, an emulsifier, a foam stabilizer and an
emollient. The Oil Phase is typically heated to about 80.degree. C.
to about 85.degree. C. An Active Phase composition is preferably
prepared by dissolving and mixing one or more of an anesthetic
agent and/or an anti-inflammatory agent with purified water.
[0050] The Oil Phase is typically added to the Water Phase, mixed,
and cooled. To this, preferably, the acid/acid salt composition is
added, with mixing, and to this the Active Phase is preferably
added, with continued mixing. The pH of the resulting composition
is adjusted to the desired level using either base or acid, and any
desired optional agents, such as anesthetics or anti-inflammatory
agents, are then added to the composition, as disclosed in the
Examples.
[0051] Deodorized Compositions
[0052] One of the problems associated with neutralizing the
alpha-hydroxy acid with ammonium hydroxide is that in the reaction
product, free or unreacted ammonia is present. In dermatological
preparations, such as lotions and creams, that contain low
concentrations of reactive product, the unreacted ammonia is not
often noticeable nor objectionable. At higher concentrations of the
reactive product, however, such as neutralized alpha-hydroxy acid
greater than 10% by weight, unreacted ammonia from the
dermatological preparations can give off a strong, unpleasant
ammonia odor. Currently available products having a high percentage
of unreacted ammonia employ fragrances to mask the unpleasant odor
of ammonia. A disadvantage to the use of fragrances to mask the
odor is that many patients who require treatment with high
concentrations of alpha-hydroxy acids are at the same time allergic
to such fragrances and may experience irritation and stinging.
Often the diseased skin becomes abraded or broken. Use of
fragrances in products applied to the skin may result in unpleasant
side effects. A further problem associated with high concentrations
of the neutralized alpha-hydroxy acids is that the preparations
occasionally develop a yellow coloration over time.
[0053] In order to prepare a deodorized composition of the present
invention, the alpha-hydroxy acid is combined with ammonium
hydroxide, to provide a neutralized acid solution containing
unreacted ammonia. Before combining the neutralized acid solution,
containing unreacted ammonia, with the selected anesthetic and/or
anti-inflammatory agents or other ingredients, the reaction product
is contacted with activated carbon. The activated carbon purifies,
decolorizes, and removes odor from the composition by absorbing
unreacted ammonia, and other impurities that may be present in the
composition, onto the surface of the carbon particles. The
deactivated carbon has an extremely large surface area per unit
weight making it an efficient absorptive material. The `activation`
of carbon in its manufacture produces many pores within the carbon
particles. It is the vast area of the walls within these pores that
accounts for most of the total surface area of the carbon.
[0054] Activated carbon adsorption is a time-release phenomenon
that takes place in three steps. Initially, impurities in solution
contact the external surface of a carbon particle as the liquid
passes through the carbon bed. Secondly, impurities diffuse into
the pores of the carbon particle. Finally, impurities are attracted
to the pore wall and held by electrostatic (physical) or chemical
forces. The adsorption method required to deodorize the
compositions of the present invention is dependent on contact time
with the carbon, unreacted ammonia concentration, impurity
concentration, and adsorption affinity.
[0055] Deodorizing methods of the present invention preferably
include passing the neutralized solution, containing unreacted
ammonia, through an activated carbon cartridge to provide a
deodorized filtrate. The filtrate is then typically combined with
one or more anesthetic agents described above and/or one or more
anti-inflammatory agents described above, providing a composition
for use in dermatological formulations.
[0056] Methods of the present invention alternatively include
forming a slurry of activated carbon particles and neutralized acid
solution containing unreacted ammonia, which is then filtered to
provide the deodorized composition of the present invention. A
preferred method for large scale commercial preparation involves
adding activated carbon to the neutralized solution to form a
slurry which is stirred prior to filtering. The amount of activated
carbon necessary in the method of the present invention may vary
from about 30% to about 75% by weight of the total aqueous solution
of the neutralized alpha-hydroxy acid. The slurry of the activated
carbon and neutralized acid is stirred at ambient temperatures for
about 15 minutes to about 2 hours. Following this treatment, the
carbon is filtered off and the deodorized filtrate is combined with
the selected anesthetic and/or anti-inflammatory agents.
[0057] Optional Additives
[0058] The resulting composition is used to prepare dermatological
formulations in the form of, for example, creams and lotions, in
accordance with well known procedures. Such formulations are well
known to those of skill in the art. Examples of additives, as
indicated above, which may be used in formulating creams include,
but are not limited to, petrolatum, non-ionic surfactants, mineral
oil, long-chain alcohols, and fatty acids. Examples of additives
used in formulating lotions include, but are not limited to,
propylene glycol and non-ionic surfactants.
EXAMPLES
[0059] Objects and advantages of this invention are further
illustrated by the following examples, but the particular materials
and amounts thereof recited in these examples, as well as other
conditions and details, should not be construed to unduly limit
this invention.
Examples 1-4
[0060] Preparation of Compositions Containing Anti-Inflammatory
and/or Anesthetic Agents
[0061] Four preferred formulations, Formulations A-D, of a
moisturizing cream are listed in Table 1. These compositions were
made using the following procedure:
[0062] Ammonium Lactate Solution
[0063] A 50-70% ammonium lactate solution was purchased from
Pfanstiehl Labs (Waukegan, Ill.) or PURAC America (Lincolnshire,
Ill.).
[0064] Gum Phase Preparation
[0065] A portion of the purified water was measured into a jacketed
kettle. The water was haled to about 80.degree. C. to about
85.degree. C. and mixed. With continued mixing, the magnesium
aluminum silicate, NF (Vanderbilt, Norwalk Conn.) and methyl
cellulose, USP, (Dow Chemical, Midland, Mich.) were added to the
water. The Gum Phase was mixed for at least 45 minutes, until
uniform, while maintaining a temperature of about 80.degree. C. to
about 85.degree. C.
[0066] Water Phase Preparation
[0067] To a jacketed compounding kettle the following ingredients
were added using a transfer pump: hot purified water, USP, and
glycerin, 99.5%, USP (Dow Chemical, Midland, Mich.). The transfer
pump was rinsed with additional purified water. The Water Phase was
mixed. The Gum Phase was transferred to the Water Phase using a
transfer pump fitted with a 60 mesh screen. The Gum Phase kettle
was rinsed with additional hot purified water, USP. The Water Phase
and Gum Phase mixture was mixed for at least about 15 minutes while
adjusting the temperature to about 80.degree. C. to about
85.degree. C. The methylparaben (Napp Technologies, Saddlebrook,
Ill.) was added. The Water/Gum Phase was mixed for about 20 minutes
to about 35 minutes while maintaining a temperature of about
80.degree. C. to about 85.degree. C.
[0068] Oil Phase Preparation
[0069] To a jacketed compounding kettle the following ingredients
were added:
[0070] light mineral oil, NF (Penreco, Karns City, Pa.), propylene
glycol, USP (Dow Chemical, Midland, Mich.), laureth-4 (Uniqema, New
Castle, Del.), a glyceryl stearate and PEG-100 stearate blend
(Uniqema, New Castle, Del.), polyoxyl-40-stearate, NF (Uniqema, New
Castle, Del.), cetyl alcohol, NF (Croda, Parsippany, N.J.),
DIMETHICONE 350 (Dow Corning, Midland, Mich.), and propylparaben,
NF (Napp Technologies, Saddlebrook, Ill.). The ingredients were
mixed and heated to about 80.degree. C. to about 85.degree. C.
[0071] Active Phase Preparation
[0072] Into a compounding kettle purified water, USP, was weighed
out. The pramoxine HCl, USP (Abbott Labs, Waukegan, Ill.) was added
to the water. The solution was mixed until the pramoxine HCl was
dissolved.
[0073] Emulsion Phase
[0074] When the temperatures of the water and oil phases were about
80.degree. C. to about 85.degree. C. the oil phase was added to the
water phase using a transfer pump. The emulsion was mixed for at
least about 30 minutes. The emulsion was cooled with ambient water
while mixing until the batch temperature reached was about
45.degree. C. to about 50.degree. C. When this temperature was
reached, the ammonium lactate solution was added using a transfer
pump. The pump was rinsed with purified water, USP. Active vacuum
was applied to the emulsion at about 12 inches Hg. to about 14
inches Hg. Cooling and mixing continued until the emulsion reached
about 39.degree. C. to about 41.degree. C. The vacuum was released
and the active phase was added using a transfer pump with continued
mixing. The transfer pump was rinsed with additional purified
water, USP. Active vacuum was applied at about 12 inches Hg to
about 14 inches Hg. (about 0.40 atm. to about 0.47 atm.) while
cooling continued until a product temperature of about 37.degree.
C. was reached. When the batch reached about 37.degree. C., vacuum
was released, the cooling water drained from kettle jacket and
steam applied to jacket for about 60 seconds to about 90 seconds to
relieve emulsion plating on the kettle walls. The vacuum was
reapplied at about 12 inches Hg to about 14 inches Hg. (about 0.40
atm. to about 0.47 atm). Ambient cooling water was reapplied to the
jacket and the batch was cooled to about 35.degree. C.
[0075] pH Adjustment
[0076] A sample of the emulsion was removed. The pH was measured.
If it was within about 4.5 to about 5.5, the batch was complete. If
the pH was not within this range, either strong ammonia solution
was added to increase the pH or lactic acid, USP was added to
decrease the pH. Mixing was continued while the pH was
adjusted.
TABLE-US-00001 TABLE 1 Percentages by weight Ingredient Formula A
Formula B Formula C Formula D Purified Water, USP 45.80 45.80 44.80
45.9 Methylparaben, NF 0.15 0.15 0.15 0.15 Glycerin, 99%, USP 4.00
4.00 4.00 4.00 Methyl cellulose, NF 0.001 0.001 0.001 0.001
Magnesium Aluminum 1.5 1.50 1.50 1.50 Silicate, NF Light Mineral
Oil, NF 10 10.00 10.00 10.00 Propylene Glycol, USP 5.00 5.00 5.00
5.00 Glyceryl Stearate (and) 5.00 5.00 5.00 5.00 PEG-100 Stearate
(pre-blended) Polyoxyl-40-stearate, NF 1.00 1.00 1.00 1.00 Cetyl
Alcohol, NF 1.00 1.00 1.00 3.00 Propylparaben, NF 0.05 0.05 0.05
0.05 Laureth-4 1.5 1.50 1.50 1.50 DIMETHICONE 350 0 0 0 1.00
Pramoxine HCl, USP 0 1.00 1.00 1.00 Hydrocortisone Acetate, 1.00 0
1.00 0 USP Ammonium Lactate, 24.00 24.00 24.00 21.90 60%.sup.1
Lactic Acid 12.10 12.10 12.10 12.00 Concentration .sup.1Actual
amount varies depending on the potency of ammonium lactate solution
to be equivalent to 12% lactic acid. Ammonium Lactate is a 50%-70%
solution, Formulas A through C, calculation is based on 60%.
Nominal percentage is shown for Formula D.
Examples 4-6
Multiple Counter Ion Cream Formulations
[0077] Three preferred formulations, Formulations E-G, of
moisturizing creams which, according to the present invention,
incorporate ammonium and metal ion salts along with the acid/acid
salt composition, are listed in Table 2. These compositions were
made using the following procedure:
[0078] Hot Water/Active Phase
[0079] Water, methylparaben (Napp Technologies, Saddlebrook, Ill.),
glycerin 99.5% (Dow Chemical, Midland, Mich.), and propylene glycol
(Dow Chemical, Midland, Mich.) were combined and heated with mixing
to about 70.degree. C. to about 75.degree. C. in a covered vessel.
Active ingredients, such as pramoxine HCl (Abbott Labs, Waukegan,
Ill.) or hydrocortisone acetate (Ceres Chemical, White Plains,
N.Y.) were optionally added to the hot water phase to provide a hot
water/active phase.
[0080] Oil Phase
[0081] Mineral oil (Penreco, Karns City, Pa.), stearic acid (Croda,
Parsippany, N.J.), and self-emulsifying wax (POLAWAX, Croda,
Parsippany, N.J.) was combined and heated with stirring to about
68.degree. C. to about 72.degree. C.
[0082] Emulsion Phase
[0083] The hot water/active phase was preferably added to the oil
phase when each phase was within the specified temperature range to
provide an emulsion. The emulsion was cooled until it reached about
40.degree. C. to about 45.degree. C. The lactate solutions were
preferably added and mixing continued until smooth and well
blended.
TABLE-US-00002 TABLE 2 Percentages by weight Ingredient Formula E
Formula F Formula G Water 52.45 45.05 45.05 Methylparaben, USP 0.15
0.15 0.15 Glycerin 99.5%, USP 4.0 4.0 4.0 Propylene Glycol 5.0 5.0
5.0 Light Mineral Oil 10.0 10.0 10.0 Stearic Acid 5.0 8.0 8.0
Self-emulsifying wax (POLAWAX) 7.0 8.0 8 Ammonium Lactate, 70% 5.2
5.8 5.8 Sodium Lactate, 60% 5.6 6.5 6.5 Potassium Lactate, 60% 5.6
6.5 6.5 Pramoxine HCl, USP 0 1.0 0 Hydrocortisone Acetate, USP 0 0
1.0 TOTAL 100 100 100 Actual Lactic Acid Concentration 7.6 8.8
8.8
Examples 7 and 8
Formulation for a Deodorized Lotion and Cream
TABLE-US-00003 [0084] Percentage by Weight Raw Material Lotion
Cream Purified water, USP 49.199 48.799 Ammonium lactate solution
22.00* 22.00* Light mineral oil, NF 10.0 10.00 Glyceryl stearate
(and) PEG-100 stearate 3.00 5.00 Propylene glycol, USP 5.00 5.00
Glycerin, USP 99.5 4.00 4.00 Laureth-4 1.50 1.50 Magnesium aluminum
silicate, NF 1.50 1.50 Polyoxyl-40-stearate, NF 1.00 1.00 Cetyl
alcohol, NF 0.60 1.00 Methylparaben, NF 0.15 0.15 Propylparaben, NF
0.05 0.05 Methylcellulose 0.001 0.001 *Deodorized as described
below.
[0085] Procedure
[0086] All raw materials were weighed and the mixer was
prepared.
[0087] Water Phase
[0088] The purified water was heated to about 90.degree. C. to
about 95.degree. C. At a moderate mixing speed, the magnesium
aluminum silicate (Vanderbilt, Norwalk, Conn.) was added. With
continued moderate mixing, the methylcellulose (Dow Chemical,
Midland, Mich.) and glycerin (Dow Chemical, Midland, Mich.) were
added, maintaining the temperature of about 90.degree. C. to about
95.degree. C. Moderate mixing was continued until the water phase
was uniform, at least about 2 minutes, maintaining a temperature of
about 90.degree. C. to about 95.degree. C. To this composition the
methylparaben (Napp Technologies, Saddlebrook, Ill.) was added,
with continued moderate mixing. Mixing was maintained for at least
about 10 minutes, until the composition was smooth and homogeneous,
while adjusting the temperature to about 80.degree. C. to about
85.degree. C.
[0089] Oil Phase (in a Separate Container)
[0090] In a separate container, the light mineral oil (Penreco,
Karns City, Pa.), the glyceryl stearate and PEG-100 stearate
mixture (Uniqema, New Castle, Del.), propylene glycol (Dow
Chemical, Midland, Mich.), polyoxyl-40-stearate (Uniqema, New
Castle, Del.), cetyl alcohol (Croda, Parsippany, N.J.),
propylparaben (Napp Technologies, Saddlebrook, Ill.), and laureth-4
(Uniqema New Castole, Del.) were combined and mixed at low speed,
150 rpm, while they were heated to about 80.degree. C. to about
85.degree. C. until the ingredients were completely melted and the
composition was uniform.
[0091] Emulsion Phase
[0092] When the temperatures of both the water and oil phases were
at about 80.degree. C. to about 85.degree. C., the oil phase was
added to the water phase while mixing at about 270 revolutions per
minute (rpm) for about 15 minutes. Mixing was continued at about
102 to about 135 rpm for at least about 45 minutes. The composition
was then cooled while mixing at about 141 to about 179 rpm until
the temperature of the composition reached 40.degree. C. or below.
The ammonium lactate (Pfanstiehl Labs, Waukegan, Ill., or PURAC
America, Lincolnshire, Ill.) was then added, and the composition
was cooled, with mixing at about 140 to about 165 rpm, until the
composition was smooth and uniform, with a final temperature of
about 33.degree. C.
[0093] Preparation of a Deodorized Composition
[0094] In addition to preparing a neutralized acid solution from
alpha-hydroxy acid and ammonium hydroxide, such neutralized
preparations may be purchased. Nondeodorized ammonium lactate can
be purchased from several sources, for example, from PURAC America
(Lincolnshire, Ill.). The product is a liquid containing between
58%-64% lactate and 8%-12% ammonium. Lactic acid is produced by
fermentation from sugars and is neutralized with ammonium hydroxide
to produce ammonium lactate. The method for deodorizing ammonium
lactate involves producing a slurry of ammonium lactate with about
30 weight percent per volume of total solution of activated
charcoal and mixing for about 30 minutes. The slurry is then
filtered to remove the activated charcoal. The resulting solution
of ammonium lactate is deodorized. An additional benefit to
filtering with activated charcoal is that any impurities that may
cause an off color are also removed, leaving a clear solution. The
deodorized ammonium lactate is then combined with one or more
anesthetic and/or anti-inflammatory agents.
[0095] Deodorizing Using an Activated Carbon Cartridge
[0096] Using an activated carbon cartridge, one liter of ammonium
lactate is passed through the cartridge. The resulting solution has
no odor or color.
[0097] Deodorizing Using a Slurry
[0098] Five hundred kg of activated carbon/charcoal is added to a
stainless steel vessel containing 1000 liters of ammonium lactate.
The slurry is stirred for a minimum of 30 minutes, then is
filtered. The resulting odorless and colorless filtrate is used to
prepare creams and lotions.
[0099] The complete disclosures of the patents, patent documents,
and publications cited herein are incorporated by reference in
their entirety as if each were individually incorporated. Various
modifications and alterations to this invention will become
apparent to those skilled in the art without departing from the
scope and spirit of this invention. It should be understood that
this invention is not intended to be unduly limited by the
illustrative embodiments and examples set forth herein and that
such examples and embodiments are presented by way of example only
with the scope of the invention intended to be limited only by the
claims set forth herein as follows.
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