Title: Warming and
nonirritating lubricant compositions and method of comparing irritation
United States Patent: 7,005,408
Issued: February 28, 2006
Inventors: Ahmad; Nawaz (Monmouth
Junction, NJ); Sun; Ying (Belle Mead, NJ); Lin; Shun Y. (Plainsboro, NJ)
Assignee: McNeil-PPC, Inc. (Skillman, NJ)
Appl. No.: 137509
Filed: May 1, 2002
Web Seminars -- Pharm/Biotech/etc.
This invention relates to substantially
anhydrous warming, non-toxic and nonirritating lubricating compositions
containing polyhydric alcohols and an insulating agent. The invention also
relates to methods of using such compositions for lubrication,
administration of active ingredients and for preventing or treating
Description of the Invention
FIELD OF THE
This invention relates to personal
lubricant compositions that are warming and nonirritating when applied to
the skin or mucous membranes, especially the vaginal or oral mucosa. The
compositions of this invention are substantially anhydrous and contain one
or more polyhydric alcohol. This invention also relates to the method that
can be used to test and compare the irritation of the compositions of this
invention and other personal lubricants known to the art.
BACKGROUND OF THE
In the field of personal lubricants and
medicaments applied to mucosal membranes, from time to time attempts have
been made to overcome the problem of the perception of cold. When an
individual applies personal lubricant or medicament such compositions to
internal mucosal membranes, often an individual experiences an
uncomfortable, cold feeling due to the difference in temperature between
the body and the ambient temperature.
An appreciable number of personal lubricant compositions are known to the
art. These compositions range from jellies to liquids to vaginal
suppositories and vary from being aqueous to oils to silicone based. The
majority of the compositions actually used today are aqueous jellies or
aqueous liquids. Almost all personal lubricants known and available for
use today are cold to touch, a feeling that can be uncomfortable.
A number of compositions are known to the trade or described in the
literature that claim to impart a warming sensation upon application to
the skin or mucosa. Some of these compositions use plant extracts which
are irritating to the skin and mucous membranes and give a feeling or
perception of warmth by virtue of their irritant action. Others claim to
enhance blood flow in order to cause tissue warming. Still others are
alleged to work on the principle of freezing point depression and are well
suited for heating in a microwave or cooling in a refrigerator. There is
one cosmetic composition rendered self-heating by inclusion of compound
containing a boron-to-boron linkage, which reacts exothermally with water.
One example of a composition known to the trade, Prosensual™, distributed
by Lexie Trading, Inc., Fairlaw, N.J., contains plant extracts such as
Cinnamon cassia (Cinnamon), Zingiber officinalis (Ginger), Mint,
Sandalwood, Orange and Clove, which are all known to be skin irritants.
Such a composition has the disadvantage of causing irritation to the
mucosa, which can be problematic in relation to the vaginal or oral mucosa
as irritation may promote the growth of unwanted bacteria and cause
Another current composition, WET™ Heating Massage Oil, distributed by
International, Valencia, Calif., uses Retinyl Palmitate (Vitamin A
Palmitate), Prunus amygdalis (Prunes), Amara (Almond),
Persica gratissima (Avacado Oil), Macdamia ternifulia Seed Oil,
Kakeri Nut Oil, Helianthus annus (hybrid Sunflower), Cannabis
sativa (Hemp) Seed Oil and Aloe vera. Most of these ingredients are
known irritants that are not suitable for use on mucous membranes.
U.S. Pat. No. 5,895,658, entitled "Delivery of L-Arginine to Cause Tissue
Warming, Sustained Release of Nitric Oxide to treat effects of Diabetes,
Stimulate Hair Growth and Heal Wounds," describes a preparation for
producing enhanced blood flow in tissues thus causing beneficial effects,
such as warming cold tissues of hands and feet.
U.S. Pat. No. 5,513,629 entitled "Microwavable Heat Releasing and
Absorbing Compositions and Container, Pliable Gel Comprising Humectant,
Freezing Point Depressant, Gel Sealer, Polyacrylamide Absorbent, Corn
Starch Binder, Mineral Oil and Plasticizers, Durability, Efficacy"
describes compositions that have a high vapor points and are, therefore,
suited for heating in a microwave oven or cooling in a freezer and
placement in a suitable container or vinyl package, such as a hot-and-cold
pack, but not for human consumption or use.
However, none of the foregoing compositions are actually "warm", or at a
relatively higher temperature than the ambient temperature of the product
or the surrounding environment.
U.S. Pat. No. 4,110,426, entitled "Method of Treating Skin and Hair with a
Self Heated Cosmetic, Organic Boron-Oxygen-Boron Compounds" describes
non-aqueous compositions such as shaving creams, that are rendered
self-heating by including therein a compound containing at least one
boron-oxygen-boron linkage, such as triethoxyboroxine. The
boron-containing compound reacts exothermally with water or other protic
material to increase temperature. Such compositions are not suitable for
vaginal or oral use due to the potential toxicity of boron-containing
compounds to the human reproductive system (Fail P A, et al., general,
reproductive, developmental, and endocrine toxicity of boronated compounds.,
Reprod toxicol 12: 1, 1-18, January-February, 1998).
Physical energy forms have been utilized to enhance material transport
across a membrane for therapeutic purposes. Such energy forms include
electricity, ultrasound and thermal energy (e.g., heat-assisted drug
delivery), (reviewed by Sun, in "Skin Absorption Enhancement by Physical
Means: Heat, Ultrasound, and Electricity", Transdermal and Topical Drug
Delivery Systems, Interpharm Press, Inc., 1997, pages 327-355). Local
heating of a drug delivery system or formulation, as well as the skin or
mucosal tissues, not only increases thermodynamic energy of drug molecules
and membrane permeability to facilitate drug movement across a barrier
membrane, it improves blood circulation in the tissue to expedite drug
removal from the local tissue into the systemic circulation. Both
processes leads to an enhanced absorption of the drug. Experimental
evidence demonstrates that low-level heating (i.e., a tissue temperature
of less than about 42° C.) significantly enhances percutaneous drug
U.S. Pat. No. 5,658,583 describes a heat-generating apparatus for improved
dermal permeation of pharmaceuticals. The apparatus includes a thin drug
formulation reservoir and a heat-generating chamber of oxidation reaction
separated by a non-permeable wall. The drug formulation reservoir houses a
predetermined amount of a formulation containing pharmaceutical agents.
The heat-generating/temperature-regulating chamber includes a
heat-generating medium consisting of carbon, iron, water and/or salt which
is activated upon contact with oxygen in the air. However, a complicated
heating device such as this is not suitable for use in the vaginal or oral
cavity for obvious safety concerns.
Locally applied heat (such as an abdominal heating patch) has also been
used to treat dysmenorrhea, or menstrual cramps, with demonstrated
efficacy (Akin M D et al., Continuous low-level topical heat in
the treatment of dysmenorrhea., Obstet Gynecol 97: 3, 343-9, March,
U.S. Pat. No. 6,019,782 describes disposable thermal body pads with heat
generation via an oxidation reaction intended for relieving menstrual pain
when applied onto the abdominal skin. There is currently a commercial
product in the U.S. market for dysmenorrhea treatment based on abdominal
heating, ThermaCare® Air-Activated Heatwraps, Menstrual Cramp Relief
patches manufactured by Procter & Gamble (Cincinnati, Ohio). However,
there are no products or description of internal localized heating to
SUMMARY OF THE
The compositions and methods of this
invention relate to warming lubricant compositions that are non-toxic and
non-irritating and that can be used as personal lubricants designed to
come into contact with the skin or mucosa. When mixed with water, the
compositions of this invention increase in temperature or generate warmth.
This has a soothing effect on the tissues to which these compositions are
The compositions of this invention may be applied to the skin or mucous
membranes, preferably the vaginal or oral mucosa. The compositions of this
invention are preferably substantially anhydrous and preferably contain at
least one polyhydric alcohol.
We theorize that, when the polyhydric alcohols contained in the
compositions of this invention come into contact with water or body
moisture in humans, they react with the ambient water molecules to cause
an increase in temperature or generate warmth, thus having a soothing
effect on the tissues to which these compositions are applied.
Surprisingly, and contrary to the general belief that polyhydric alcohols
in compositions are irritating to the mucosa, compositions of this
invention containing such polyhydric alcohols have been found to be
non-irritating. In fact, these compositions are very mild to the skin and
mucous membranes. The compositions of this invention are soothing when
applied to oral mucous membranes and may function to relieve minor
irritation of the mouth and throat.
The combination of polyhydric alcohols in the compositions of this
invention may also be used as a vehicle to solubilize otherwise insoluble
drugs, including, but not limited to, antifungals, antibacterials,
antivirals, analgesics, anti-inflammatory steroids, contraceptives, local
anaesthetics, hormones and the like.
The compositions of this invention also preferably contain an insulating
agent which functions to preserve the temperature increase by maintaining
the heat within the composition after it has been applied to the skin or
mucosa. More preferably, honey may be utilized as an insulating agent.
OF THE PREFERRED EMBODIMENTS
The compositions of this invention are
substantially anhydrous, preferably containing less than about 20% water,
more preferably containing less than about 5% water and, most preferably,
containing less than about 3% water. Preferably, the compositions of this
invention contain at least one polyhydric alochol, and more preferably,
two polyhydric alcohols. Preferably the polyhydric alcohol portion of the
compositions of this invention one or more polyhydric alcohols such as
alkylene glycols and others selected from the following group: glycerin,
propylene glycol, butylene glycol, hexalene glycol or polyethylene glycol
of various molecular weight and the like and/or combination thereof. More
preferably, the compositions of this invention contain a polyethylene
glycol; most preferably, the polyethylene glycol may be selected from the
following group: polyethylene glycol 400 or polyethylene glycol 300. The
compositions of this invention should contain polyhydric alcohols in an
amount from about 80% to about 98% by weight of the composition.
The compositions of this invention preferably also contain an insulating
agent. More preferably, the insulating agent should be honey or esters of
isopropyl alcohol and saturated high molecular weight fatty acids such as
myristic or palmitic acid, e.g., isopropyl myristate and isopropyl
palmitate. The insulating agent should be present in the compositions of
this invention in an amount of from about 1% to about 5% by weight of the
The compositions of this invention are unexpectedly self-preserving and
may not require a preservative. However, a preservative may be added to
impart an additional guarantee against microbial growth. A preservative
may be selected from preservatives known to those of skill in the art,
including, but not limited to, one or more of the following: methylparaben,
benzoic acid, sorbic acid, gallic acid, propylparaben or the like. The
preservative may be present in the compositions of this invention in an
amount from about 0.01% to about 0.75% by weight of the composition.
The compositions of this invention may also preferably contain an ester.
More preferably, the ester is a fatty acid ester. Most preferably, the
ester may include, but is not limited to: isopropyl stearate, isopropyl
myristate, isopropyl palmitate, isopropyl laurate and the like. Most
preferably, the ester is isopropyl myristate.
The compositions of this invention may contain one or more water-soluble
cellulose-derived polymers, gums, chitosans or the like. Such polymers
contribute to the viscosity and bioadhesiveness of the compositions of
this invention. Preferably, such cellulose-derived polymers are
hydroxyalkylcellulose polymers. More preferably, the hydroxyalkylcellulose
polymer is hydroxypropylcellulose or Klucel®, available commercially from
Hercules Incorporated, Wilmington, Del.
The polyhydric alcohols used in the compositions of this invention are
theorized to be useful as warming and heat-generating agents. Honey
functions as an insulating agent, protecting the compositions from
becoming too cold. The ester, preferably a fatty acid ester, functions as
an emollient and lubricant. The cellulose polymer is useful as a viscosity
building agent. The compositions of this invention are unique in that they
lubricate, warm and soothe the tissues of the user, especially the oral
and vaginal mucous membranes, without conveying a feeling of cold.
Moreover, they are smooth and lubricating.
The compositions of this invention may be a liquid, a semi-solid, or a
solid depending upon the particular intended use thereof. The compositions
of this invention may also be formulated into soft or hard gelatin
capsules, suppositories and impregnated into fabrics or polymers.
The compositions of this invention may be used as personal lubricants
which convey a feeling of warmth. The feeling of warmth generated by the
compositions of this invention is soothing to the skin or mucous membranes
where they are applied. The compositions of the invention also possess a
sweet and pleasant taste, which is of particular benefit when these
compositions are used orally.
The compositions of this invention may also be used as personal
moisturizers, which convey a feeling of warmth when applied to vaginal or
The compositions of this invention may also be used as a vehicle to
deliver medication or other treatment agents to the biomembranes
including, but not limited to, hormones, antimicrobial or antifungal
agents and the like. The antifungal agents is preferably an azole or
imidazole, including but not limited to, miconazole, econazole,
terconazole, saperconazole, itraconazole, butaconazole, clotrimazole,
tioconazole, fluconazole and ketoconazole, vericonazole, fenticonazole,
sertaconazole, posaconazole, bifonazole, oxiconazole, sulconazole, elubiol,
vorconazole, isoconazole, flutrimazole and their pharmaceutically
acceptable salts and the like. Other antifungal agents may include an
allylamine or one from other chemical families, including but not limited
to, ternafine, naftifine, amorolfine, butenafine, ciclopirox, griseofulvin,
undecyclenic acid, haloprogin, tolnaftate, nystatin, iodine, rilopirox,
BAY 108888, purpuromycin and their pharmaceutically acceptable salts.
Another embodiment of the invention are compositions for vulvovaginal use
containing one or more antibiotics. The antibiotic may be chosen from the
group including, but not limited to, metronidazole, clindamycin,
tinidazole, ornidazole, secnidazole, refaximin, trospectomycin,
purpuromycin and their pharmaceutically acceptable salts and the like.
Another embodiment of the compositions of this invention include
compositions for vulvovaginal use containing one or more antiviral agents.
Antiviral agents may preferably include, but are not limited to,
immunomodulators, more preferably imiquimod, its derivatives, podofilox,
podophyllin, interferon alpha, reticolos, cidofovir, nonoxynol-9 and their
pharmaceutically acceptable salts and the like.
Still other embodiments of the compositions of this invention are
compositions that include one or more spermicides. The spermicides may
preferably include, but are not limited to, nonoxynol-9, octoxynol-9,
dodecaethyleneglycol monolaurate, Laureth 10S, and
Methoxypolyoxyethyleneglycol 550 Laurate and the like.
Still other embodiments of the compositions of this invention are
compositions containing antimicrobial agents. The antimicrobial agents may
preferably include, but are not limited to, chlorohexidine gluconate,
sodium polystyrene sulfonate, sodium cellulose sulfate, silver particles
of micro- and sub-micrometer sizes, silver salts and other antibacterial
agents known to the art.
Yet other embodiments of the compositions of this invention are
compositions that may include local anesthetics. The local anesthetics may
preferably include, but are not limited to, benzocaine, lidocaine,
dibucaine, benzyl alcohol, camphor, resorcinol, menthol and
diphenylhydramine hydrochloride and the like.
Compositions of the invention may also include plant extracts such as
aloe, witch hazel, chamomile, hydrogenated soy oil and colloidal oatmeal,
vitamins such as vitamin A, D or E and corticosteroids such as
Another embodiment of the compositions and methods of this invention
include compositions for vulvovaginal use containing one or more hormones
for treating a decrease in estrogen secretion in the woman in need of
estrogen replacement such as women with vaginal atrophy. The hormones may
preferably include, but are not limited to, estrogen selected from the
group consisting of estradiol, estradiol benzoate, estradiol cypionate,
estradiol dipropionate, estradiol enanthate, conjugated estrogen, estriol,
estrone, estrone sulfate, ethinyl estradiol, estrofurate, quinestrol and
Another embodiment of the compositions and methods of this invention
include compositions for vulvovaginal use containing one or more
analgesics and/or nonsteroidal anti-inflammatory agents for treating
dysmenorrhea or mentrual cramping. The analgesics and nonsteroidal
anti-inflammatory agents may preferably include, but are not limited to,
aspirin, ibuprofen, indomethacin, phenylbutazone, bromfenac, fenamate,
sulindac, nabumetone, ketorolac, and naproxen and the like.
Yet another embodiment of the compositions and methods of this invention
include compositions for oral and vulvovaginal use relates to a method of
enhancing the absorption of active agents from the applied compositions
into the mucosal membrane by increasing the composition and mucosal tissue
temperature via interaction of the polyhydric alcohols in the compositions
and moisture on the mucosa and subsequently released heat.
Yet another embodiment of the compositions of this invention include
compositions for vulvovaginal use relates to compositions and methods for
preventing and/or treating dysmenorrhea by intravaginal warming or
heating. Preferably, the composition heats the intravaginal area to a
temperature preferably between about 37° C. and about 42° C., more
preferably between about 38° C. and about 41° C. The compositions of
invention for use in such a method may optionally contain active agents
such as analgesics and nonsteroidal anti-inflammatory agents for
dysmenorrhea treatment. The composition of the invention may be
administered directly into the vagina by an applicator, or be impregnated
into vaginal devices such as tampon for intravaginal applications.
The compositions of this invention may be manufactured as a coating of a
tampon, or dispersing throughout the absorbent tampon material, or
enclosed inside as a core of a tampon. The compositions of this invention
for the warming tampon for preventing and/or treating dysmenorrhea
preferably include a mixture of polyethylene glycols of various molecular
weights produced by The Dow Chemical Company (Midland, Mich.) under the
trade names of CARBOWAX SENTRY PEG 300 NF, CARBOWAX SENTRY PEG 400 NF,
CARBOWAX SENTRY PEG 600 NF, CARBOWAX SENTRY PEG 900 NF, CARBOWAX SENTRY
PEG 1000 NF, CARBOWAX SENTRY PEG 1450 NF, CARBOWAX SENTRY PEG 3500 NF,
CARBOWAX SENTRY PEG 4000 NF, CARBOWAX SENTRY PEG 4600 NF, and CARBOWAX
SENTRY PEG 8000 NF. The compositions of this invention for dysmenorrhea
prophylaxis and treatment may contain one or more water-soluble
cellulose-derived polymers and gums that form gels around the polyhydric
alcohols such as glycerin, propylene glycol and polyethylene glycols thus
reducing the dissolution of the polyhydric alcohols, prolonging the
salvation heat release, and regulating the elevated temperature in the
preferred temperature range.
Claim 1 of 31 Claims
1. A substantially anhydrous
lubricant composition comprising at least one polyhydric alcohol and an
insulating agent wherein said insulating agent is honey.
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