US005945409A

Ulllted States Patent [19] [11] Patent Number: 5,945,409

Crandall [45] Date of Patent: Aug. 31, 1999

[54] TOPICAL MOISTURIZING COMPOSITION 4,760,096 7/1988 Sakai et a1. ........................... .. 514/786
AND METHOD 4,783,450 11/1988 FaWZi et a1. 514/78
4,981,681 1/1991 Tosti ... ... .... .. . . . . . .. 424/78

[75] Inventor: Wilson Trafton Crandall, Ft. De?ance, 5,238,933 8/1993 CM 9 91- 514/2362
Va_ 5,639,740 6/1997 Crandall .................................. .. 514/78

_ OTHER PUBLICATIONS
[73] Ass1gnee: Wilson T. Crandall, Ft. De?ance, V21.
Elias et 211., The Journal of Investigative Dermatology, v01.
[21] Appl. No.: 08/876,764 731m)- 339348, (1979) _
Lu1s1 et a1., Colloid & Polymer Science, vol. 268, pp.
[22] Filed: Jun. 16, 1997 356_374 (1990)~
ScartaZZini et a1., Journal ofPhysical Chemistry, vol. 92, pp.
Related US. Application Data 829_833 (1988)~
_ _ _ _ _ Schmo1ka,Journal ofBiomedical Material Research, Vol. 6,
[63] Continuation-m-part of application No. 08/403,241, Mar. pp 571_582 (1972)
1O 1995 Pat' NO' 563974O' Wi11iman et 211.,Journal ofPharmaceutical Sciences, Vol. 81
[51] Int. C16 ....................... .. A61K 31/685; A61K 31/23 (9), pp. 871874 (1992).
[52] US. Cl. .......................... .. 514/78; 514/159; 514/552; Merck Index, (9th Edition), p. 711 (1976).
514/847; 514/861; 514/936; 514/937; 514/944 Primary ExaminerShe11ey A. Dodson
[58] Field of Search ............................ .. 514/78, 159, 552, - _
514/847, 861, 936, 937, 944 Attorney, Agent, or Firm Jones & Askew, LLP
[57] ABSTRACT
[56] References Cited
The present invention comprises methods and compositions
U-S- PATENT DOCUMENTS for topically treating and moisturizing keratinous structures
3,062,721 11/1962 Grate ..................................... .. 424/658 of humans and animals including Skin hair ?ngernails
3,952,099 4/1976 Smith .................................... .. 514/152 toena11s> hVeS> and hmS~
3,957,971 5/1976 OleniacZ ............................... .. 424/450
4,701,471 10/1987 Loucks, Sr. et a1. ................. .. 514/784 20 Claims, N0 Drawings
 5,945,409
1 2
TOPICAL MOISTURIZING COMPOSITION Which are all epidermal derivatives. For example, cracked
AND METHOD hooves can result in lameness or in injury to the coronary
band, the primary groWth and nutritional source for the hoof
PRIOR RELATED APPLICATIONS Wall. Injuries to the coronary band can cause serious per
manent defects in the groWth of the hoof Wall.
The present application is a continuation-in-part of US.
application Ser. No. 08/403,241, ?led Mar. 10, 1995, now The formation of organogels containing lecithin dissolved
US. Pat. No. 5,639,740 Which is incorporated herein by With isopropyl palmitate or other solvents, and Water, has
reference in its entirety. been described by Luisi et al., Colloid and Polymer Science
268:356374 (1990) and ScartaZZini et al., The Journal of
10 Physical Chemistry 92:829833 (1988), Which are incorpo
TECHNICAL FIELD
rated herein by reference in their entirety. Williman et al.,
The present invention is related to a process and compo Journal of Pharmaceutical Sciences 81:871874 (1992),
sition for moisturizing and rejuvenating keratinous tissues Which is incorporated herein by reference in its entirety,
including skin, hair, ?ngernails, and toenails of humans and examined the ef?cacy of lecithin organogels for use in the
animals, and also hooves and horns of animals. More 15 transdermal delivery of drugs such as scopolamine and
particularly, the present invention relates to topically apply broxaterol. Williman et al., also observed that lecithin orga
ing the composition disclosed herein in order to treat the nogels had no detrimental effect on skin When compared to
affected keratinous tissue. control samples treated With physiological saline (see page
872, column. 2, paragraph 3, Journal of Pharmaceutical
BACKGROUND OF THE INVENTION 20 Sciences 81:871874 (1992)).
The skin is the largest organ in the body and serves several CatZ et al., in US. Pat. No. 5,238,933, discloses skin
important functions that are essential to life. The skin retards permeation enhancer systems Which increase the permeabil
dehydration and also acts as a barrier to the invasion of ity of the skin to transdermally administered, pharmacologi
various pathogens and noxious substances. Skin is com cally active agents.
25
posed of the epidermis, or upper layer, and the subjacent Smith, in US. Pat. No. 3,952,099, discloses dermatologi
dermis. The epidermis is the super?cial layer and gives rise cal compositions for enhancing the penetration of pharma
to the nails, hair, sebaceous glands, sWeat glands, and the cologically active agents, such compositions comprising a
parenchyma of mammary glands. The epidermis is com sugar ester in combination With a sulfoxide or phosphine
posed of several layers. As cells from the deeper layer, the 30
oxide.
stratum germinativum, move toWard the surface, they begin Loucks, in US. Pat. No. 4,701,471, discloses a cosmetic
to synthesiZe the intracellular protein keratin. During sub and pharmaceutical composition comprising bovine bone
sequent movement, these cells lose their distinct nuclei and marroW acids mixed With lecithin for prevention of the fatty
form the outermost layer of the epidermis knoWn as the acid oxidation and odor putrefacation.
stratum corneum Which is comprised of several layers of 35 In US. Pat. No. 3,957,971, OleniacZ discloses moistur
corni?ed epidermal cells that are embedded in an intercel iZing units for treating keratinous tissue comprising lipo
lular matrix of semi-polar and polar lipids. This layer acts as somes having a ternary lipid mixture of lecithin, dicetyl
a transport route for various drugs, such as hydrocortisone, phosphate, and a sterol.
and also acts as a barrier to the transport of other drugs and
cosmetics (Elias et al.,Journal of Investigative Dermatology Sakai et al., in US. Pat. No. 4,760,096, discloses a skin
40 moisturiZing method and preparation containing a combi
73:339348, 1979). In addition, this lipid layer of the
stratum corneum assists in the retention of Water. The Water nation of a phosphatide such as soy lecithin, and one or more
content of the stratum corneum has a profound in?uence on C1OC3O carboxylic acid sterol esters.
the appearance, ?exibility, texture, and dryness of the skin, US. Pat. No. 4,783,450 to FaWZi et al. discloses the use
and also on the absorption of drugs and other molecules into of lecithin as a skin penetration enhancer for transdermal
45
and through the skin. delivery of the drug procaterol through skin.
With increasing age, the skin gradually loses ceramides A method and composition for increasing the moisture of
and Water and becomes drier, less ?exible and supple, more epidermal structures are needed. The composition should be
Wrinkled, and scaly in appearance. One of the major objec easy to apply topically, enhance moisture retention, and also
tives of the cosmetic industry is to retard the drying and have the capacity to deliver compounds that Will assist in
Wrinkling of the skin that occurs With normal aging or as the moisturiZing and rejuvenating keratinous structures such as
result of exposure to Wind, sun, cold and chemicals. As the the skin hair, ?ngernails, toenails, hooves and horns.
mean age of the population increases, more people are
SUMMARY OF THE INVENTION
seeking products that Will retard the effects of aging on the
skin and Will essentially rejuvenate the skin. Increasing the 55 The present invention is a method of moisturiZing kera
moisture content of the skin is one mechanism for achieving tinous tissue of a human or animal comprising the step of
this objective. Furthermore, enhanced skin hydration facili topically applying to the keratinous tissue of the human or
tates the transport of pharmaceuticals across the epidermis to animal, a composition comprising lecithin, in an organic
reach the underlying dermis and subjacent capillaries of the solvent and Water Whereby the composition is delivered into
lymphatic and circulatory systems. 60 the stratum corneum, epidermis and dermis. Another
Another objective of the cosmetic industry is to retard the embodiment of the present invention comprises a method of
drying of the hair, ?ngernails and toenails, Which all arise treating keratinous tissue of a human or animal comprising
from the epidermis. In addition to enhancing the youthful the step of topically applying to the keratinous tissue of the
appearance of an individual, increased hydration of these human or animal, a composition comprising Water dispers
structures prevents the painful effects of cracked nails and 65 ible lecithin.
itchy, scaly scalp. In animals, similar problems can occur In one embodiment, the present invention provides an
With ?ngernails and toenails and also With horns and hooves easy to use therapeutic and cosmetic process for treating dry
 5,945,409
3 4
skin and for alleviating the associated irritation and cracking Yet another object of the invention is to provide a com
of the skin by topically applying the composition disclosed position and method for treating the cracked teats of animals
herein. Use of this process and composition increases the and humans to prevent mastitis.
moisture content of the skin, reduces Wrinkling, and pro Another object of the invention is to provide a composi
vides a rejuvenated appearance to the skin. In addition, this tion and method for treating dry and thinning hair of humans
invention has great utility for the treatment of dry and brittle and animals.
?ngernails and toenails, and the adjacent skin that often is
dry and cracked. In another embodiment, this invention is a Still another object of the invention is to provide a
therapeutic and cosmetic process for application to animals composition and method for treating calluses, corns, and any
With cracked and damaged horns and/or hooves. A horn or other skin conditions involving drying of the skin.
10
hoof dressing in shoW horses and cattle Would produce a These and other objects, features and advantages of the
more vibrant and healthy appearance. In addition, rapid present invention Will become apparent after a revieW of the
closure of cracks in hooves Would prevent invasion by folloWing detailed description of the disclosed embodiments
foreign material and reduce the incidence of infection. and the appended claims.
An additional embodiment of the invention is a therapeu
15 DETAILED DESCRIPTION OF THE
tic and cosmetic process for the treatment of dry and
thinning hair to provide increased hair groWth and thickness. INVENTION
It is understood that the present invention also encompasses
The present invention is a method of moisturiZing kera
a method and composition for delivery of molecules
including, but not limited, to elastin, collagen and collagen tinous tissue of a human or animal comprising the step of
fragments, glucosamine, glucosamine sulfate, glycerol, topically applying to the keratinous tissue of the human or
urea, ceramides, dimethicone, N-decylmethyl sulfoxide, animal, a composition comprising lecithin, in an organic
salicylic acid, lanolin, chondroitin sulfate, hyaluronic acid, solvent and Water Whereby the composition is delivered into
squalene, and various alpha hydroxy compounds such as the stratum corneum, epidermis and dermis. Another
lactic acid, citric acid, and glycolic acid, into the epidermis, embodiment of the present invention comprises a method of
dermis and other keratinous tissue. 25 treating keratinous tissue of a human or animal comprising
The present invention can include other pharmaceutically the step of topically applying to the keratinous tissue of the
acceptable components such as gelling agents, compounding human or animal, a composition comprising Water dispers
agents, scents and the like. The composition of the present ible lecithin. The present invention can optionally contain a
invention can also include other pharmaceutically active poloxamer With the desired poloxamer being poloxamer
agents such as antibacterial, antifungal, antiprotoZoal or 407.
antiviral agents. A preferred phospholipid for use in the present invention
This invention addresses the need for an easy-to-use is phosphatidylcholine, also knoWn as lecithin. Stedmans
topical treatment for cosmetic and therapeutic purposes of medical dictionary [21st ed., page 879] de?nes lecithin as
keratinous structures including the skin, nails, and hair of any of a group of phospholipids Which upon hydrolysis yield
humans and animals, and also for the treatment of the nails, 35 tWo fatty acid molecules and a molecule each of glycero
hair, hooves, and horns of animals. phosphoric acid and choline. There are several varieties of
Accordingly, it is an object of the invention to provide a lecithin. Lecithin is a mixture of the diglycerides of stearic,
composition and method for treating skin of humans and palmitic, and oleic acids, and palmitoleic, linoleic, linolenic,
animals, especially dry and cracked skin, to increase the and arachidonic acids, linked to the choline ester of phos
moisture of the skin. phoric acid. Soybean lecithin is a preferred lecithin and may
It is another object of the invention to provide a compo contain the folloWing acids; palmitic, stearic, palmitoleic,
sition and method for treating skin of humans and animals oleic, linoleic, linolenic and arachidonic. In some lecithins
to decrease the Wrinkled appearance of the skin. both fatty acids are saturated While others contain only
unsaturated fatty acids for example, oleic, linoleic or arachi
Still another object of the invention is to provide a
45 donic. In other lecithins one fatty acid is saturated, the other
composition and method for treating skin to rejuvenate the
unsaturated. Lecithins are found in nervous tissue, hepatic
skin and decrease the aged appearance of the skin.
tissue, cardiac tissue, in egg yolks and in soy Which consti
It is another object of the invention to provide a method tutes the most common and economical source of phosphati
for topically applying an improved composition to animal or dylcholine. It is therefore to be understood that any reference
human keratinous tissue for enhancing the penetration of herein to lecithin or phosphatidylcholine is intended to
pharmacologically active substances into keratinous tissue, include any combination of lecithin-like phospholipid com
especially the epidermis and dermis of the skin, Without pounds as is Well knoWn in the art. Examples of other
damaging the tissue or causing adverse systemic effects. phospholipids Which can be used in accordance With the
Another object of the invention is to provide a composi present invention include phosphatidylethanolamine,
tion and method for treating psoriasis. 55 phosphatidylserine, phosphatidylinositol, and phosphatidic
Yet another object of the invention is to provide a com acid. A mixture of any of the above phospholipids may be
position and method for treating ecZema and ichthyosis. also be used in the present invention. Mixtures of these
Still another object of the invention is to provide a phospholipids are present in natural soy lecithins.
composition and method for treating Windburn, chapped Lecithin is described as a hygroscopic Waxy solid Which
lips, sunburn, and skin dehyrated due to exposure to chemi only forms an emulsion after dissolution With an organic
cals. solvent. The phosphatidylcholine (PC) may be characteriZed
Another object of the invention is to provide a composi as amphiphilic because a polar head group is hydrophilic
tion and method for treating cracked ?ngernails and toenails and has tWo lipophilic carbon tails. This amphiphilic prop
of humans and animals. erty permits the surface polar heads in the aqueous phase to
Still another object of the invention is to provide a 65 contract, assuming the shape of sphere. Lecithin emulsions
composition and method for treating cracked hooves and are aggregates of micelles in Water and inherently have poor
horns of animals. stability. Williman et al., Journal of Pharmaceutical Sciences
 5,945,409
5 6
81:871874 (1992), found that PC, With a minimum purity imbalances, hypothalamic dysfunction, neurohypophyseal
of 95%, formed giant spaghetti-like micellar gels after it Was dysfunction, or other endocrine abnormalities.
dissolved in an appropriate nontoxic organic solvent. This The present invention includes a composition for topical
structure is called a lecithin organogel and is thought to have treatment of keratinous tissue comprising the folloWing
a linear rather than the usual spherical structure. While not components; lecithin, isopropyl palmitate and Water. The
Wanting to be bound by the folloWing statement, it may be combination of lecithin, isopropyl palmitate, and Water is
reasonable to assume the Water molecules at the polar head called lecithin organogel. The present invention optionally
of the PC promote additional cohesion by hydrogen bonding includes lecithin organogel in combination With an approxi
and thereby promote gel formation. Soy lecithin containing mately 20% solution of PLURONIC F-127 (BASF,
less than 95% PC Will not gel. PC of 95 % purity is expensive 10 Parsippany, N.J.), otherWise knoWn as poloxamer 407, in a
and What is needed is a composition and method Which is ratio of approximately 1:4. Other PLURONICS may be used
cost-effective as Well as safe for daily use. in the present invention. It is to be understood that the soy
lecithin of the present invention is a preferred lecithin source
The term PLURONIC refers to poloxamer compounds
and are sold collectively under the trademark PLURONIC
and may be dissolved in isopropyl palmitate to achieve a
?nal concentration in the composition of from approxi
(BASF, Parsippany, N.J PLURONIC F-127 (PL 127) 15
mately 20%90%, With a more preferred ?nal concentration
corresponds to poloxamer 407, a polyoxypropylene
polyoxyethylene block copolymer described by Schmolka in of from approximately 20%40%. Lecithins may optionally
be derived from eggs, and organs such as heart, brain and
the Journal of Biomedical Materials Research 6:571582,
1972. Other PLURONICS may be used in the present liver, and used at concentrations of approximately
invention. As used in this application, the terms PLURONIC 20 20%99%, With more preferred ?nal concentrations of from
organogel, poloxamer organogel, and polyoxyethylene/ approximately 20%40%. The composition according to the
polyoxypropylene organogel are synonymous. present invention can be in the form of lotions, salves,
creams, ointments, liposomes, sprays, or gels. The desired
The term moisturize or derivatives thereof, relates to the
conservation or enhancement of the Water content of the
form is lotions, ointments, micelles, giant micelles, and
25 salves. Liposomes are described in detail by OleniacZ in
keratinous tissue of animals and humans, With particular US. Pat. No. 3,957,971, the entirety of Which is hereby
reference to the skin, hair, nails, hooves and horns. incorporated by reference.
Topical application is used to mean local administration Solvents used in the preparation of a variety of gels,
of the composition and its various embodiments, for including lecithin gels, all of Which are appropriate in
example, in the treatment of dry skin. practicing the present invention, are described in
30
The term pharmacologically active agent relates to any ScartaZZini, et al. Journal of Physical Chemistry
chemical material or compound suitable for topical admin 92:829833, 1988, and Luisi, P. L. et al. Colloid and
istration Which includes any desired local effect on animal or Polymer Science 268:356374, 1990, both of Which are
human tissue contacted thereWith. incorporated herein by reference in their entirety. Speci?
The term pharmaceutically effective carrier is used 35 cally these solvents include the folloWing: ethyl laurate,
herein to mean any liquid, gel, salve, solvent, liquid, diluent, butyl laurate, ethyl myristate, isopropyl myristate, isopropyl
?uid ointment base, liposome, micelle, giant micelle, and the palmitate, isooctane, cyclooctane, cyclododecane, methyl
like, Which is suitable for use in contact With living animal cyclohexane, tert-butylcyclohexane, phenylcyclohexane,
or human tissue Without causing adverse physiological bicyclohexyl, 1,3,5-triisopropylbenZene, octylbenZene,
responses, and Which does not interact With the other com 40 trans-decalin, (1R)-(+)-trans-pinane, (1R)-(+)-cis-pinane,
ponents of the composition in a deleterious manner. n-pentane, n-hexane, n-heptane, n-octane, n-nonane,
By the term therapeutically effective amount of a n-decane, n-undecane, n-dodecane, n-tridecane,
molecule, drug or pharmacologically active agent is meant n-tetradecane, n-pentadecane, n-hexadecane,
a nontoxic but suf?cient amount to provide the desired n-heptadecane, 2,3-dimethylbutene, 1-hexene, 1,7
therapeutic effect. 45 octadiene, tripropyllamine, tributylamine, triisobutylamine,
The enhanced penetration caused by compositions of trioctylamine, dibutyl ether and 2-dodecen-1-yl succinic
this invention as used in topical application With this anhydride.
method, means increased penetration into the skin, and is In addition to isopropyl palmitate and isopropyl myristate,
achieved With compounds such as lecithin organogel, polox other solvents may be used in the practice of the present
amer organogel, phospholipid gels or poloxamer phospho invention. These solvents include, but are not limited to the
lipid gels including but not limited to folloWing: mineral spirits, kerosene, isooctane, petroleum
phosphatidylethanolamine, phosphatidylserine, ether, diethyl ether, benZene, toluene, methanol, ethanol,
phosphatidylinositol, and phosphatidic acid and phosphati heptanol, methyl isobutyl ketone, cyclohexanone, methyl
dylcholine optionally combined With n-decylmethyl sulfox ene chloride, choloroform, chlorodi?uoromethane,
ide (NDMS), PLURONIC F127, ethoxy diglycol, ethanol, 55 tetrahydrofuran, oleyoleate, 2-octyldodecanol, cetyl and
or cholesterol. Enhanced penetration can be observed in stearyl 2-ethylhexanoate, n-octanol, ethyl laurate, isooctane,
many Ways knoWn to those skilled in the art. cyclopentane, cyclohexane, and cycloheptane.
The term keratinous tissue as used herein, means skin, In a preferred embodiment, lecithin organogel may be
?ngernails, toenails, hooves, horns and hair, and any other made from PHOSPHOLIPON 90 (American Lecithin Co.,
cells containing keratin. The present invention provides a 60 Oxford, Conn.). In this embodiment, lecithin organogel
method and composition for topically treating damaged or comprises 1:1 to 1.5 :5 (Weight/vol) of PHOSPHOLIPON 90
diseased keratinous tissue resulting from any number of to isopropyl palmitate. Water is added to form the desired
causes including, but not limited to: aging; chemical drying; gel. Other penetrating agents including, but not limited to
radiation; burns from Wind, sun, ?re, cold, frostbite, radia cholesterol (2% to 100%) With a preferred range of choles
tion or chemicals; and dehydration resulting from skin 65 terol to PHOSPHOLIPON 90 of 3:7 to 3:10. These ingre
disease, abrasion, sun, chemicals, Wind, cold, ?re, renal dients are combined With sufficient ethanol to solubiliZe the
disease, colonic disease, hemorrhage, vasopressin mixture. Ethanol is subsequently evaporated, leaving a com
 5,945,409
7 8
plex of cholesterolzPHOSPHOLIPON 90. Alternatively, the present invention also encompasses a method and com
3.5%8% ethanol may be retained in the complex to position for delivery of molecules into the skin. These
enhance penetration. molecules optionally include, but are not limited to, elastin,
NDMS (PCAA Kinghurst, Houston, Tex.) is optionally elastin fragments, elastin-glycolic acid, collagen, collagen
present in the composition of the present invention at a fragments, yeast extracts (skin respiratory factor),
concentration of betWeen approximately 0.1% and 1% by glucosamine, glucosamine sulfate, hyaluronic acid,
Weight, With a preferred concentration of betWeen approxi hyaluronate, chondroitin sulfate, cholic acid, deoxycholic
acid, ginseng extract, aloe vera poWder, aloe vera oil, RNA
mately 0.15% and 0.8% by Weight, With the most preferred and DNA fragments, ascorbyl palmitate, ascorbic acid, reti
concentration of approximately 0.5% by Weight. NDMS is nal palmitate, 7-dehydroxycholesterol, vitamin E
dissolved in 10 mL of a 75% solution of ethanol. Finally, 10
tocopherol, vitamin E lineolate, panthenyl ethyl ester, glyc
puri?ed Water is added. Ethanol (98%) may also be used to erol ceramides, glycogen, DL-pyroglutamic acid, urea,
dissolve lecithin and then either boiled off completely or
sodium lactate, lactate, glycerin, sorbitol, oils of borage,
partially to leave a ?nal ethanol concentration of 3% to
evening primrose, black currant, almond and cannola, van
8.5%. While not Wanting to be bound by the following ishing cream (polyaxyl 40 stearate, stearic acid, cetyl alco
statement, it is believed that 3% to 8.5% ethanol may 15
enhance penetration. hol and stearyl alcohol), cholesterol, ?avenoids (rutin,
quercitin, hesperetin, hesperidenn diosmin and noringen),
Another preferred penetrating agent and delivery vehicle Witch haZel (Hamamelis Virginia), camomile (matri-caria
is lecithin organogel Which is a combination of lecithin, Camomilla linne), parsley (Petioselinum crispum), hibiscus
isopropyl palmitate, or isopropyl myristate and Water. Leci (Hibiscus sabdari?alinne), capric and caprylic triglycerides,
20
thin organogels have been described as vehicles that are amino acids (serine, lysine, glycine, alanine, arginine, aspar
useful in facilitating the delivery of loW molecular Weight tic acid, glutamic acid, hydroxyproline, proline, cysteine),
compounds transdermally (Williman, H., et al., Lecithin allantoin, sodium, calcium, potassium, phosphate, and
Organogel as Matrix for Transdermal Transport of Drugs, chloride, sodium lactate), alpha hydroxy acids (lactic,
J. Pharm. Sci., Vol. 81, 1992, Which is incorporated herein glycolic, citric, malonic and ammonium lactate), cocoa
by reference). The lecithin organogels are obtained by butter, coconut oil, jojoba oil, safflower oil, Wheat germ oil,
adding small amounts of Water to a solution of lecithin in sesame oil, selachyl alcohol, shark oil, cerebrosides,
organic solvents. Generally, lecithin organogels are prepared proanthocyanidin, farnestol, candelellila and carnuba Wax,
at room temperature by ?rst dissolving lecithin in an organic vitamin E nicotinate, manganese ascorbate, Zinc, oleyl alco
solvent such as isopropyl palmitate or isopropyl myristate hol and polysorbate 80, spermaceti, glycerol monostearate,
and then adding enough Water While stirring to obtain the beesWax, silicone oil, paraf?n Wax, oZokerit E, PEG 75
desired gel. Lecithin used in the gel preparations of the lanolin. N-decylmethyl sulfoxide is optionally included in
present invention generally contain at least 95% phosphati the composition in a ?nal concentration range of from 0.01%
dylcholine. to 1% With a preferred range of 0.1% to 0.5%.
The method and composition for the delivery of mol 35 By alloWing the passage of collagen fragments and
ecules through the skin for remoisturiZation and rejuvena elastin, for example, into the skin, the present invention
tion utiliZes isopropyl myristate (IPM), isopropyl palmitate increases the Water content in the dermis also contributing to
(IPP), and/or ethanol to dissolve lecithin Which is necessary the visco-elasticity Which decreases the appearance of
to form an emulsion. HoWever, IPP and IPM can be irritating Wrinkles. Glucosamine or glucosamine sulfate stimulates
to sensitive facial skin and may produce comedoWns. The 40 dermal collagen synthesis as Well as glycosaminoglycans in
invention discloses a method and composition Which elimi the epidermis Which are deliquescent. This further contrib
nates these risks. Ethanol is an excellent solvent as Well as utes to a decreased appearance of Wrinkles and to a more
penetration enhancer. Ethanol may be used to dissolve the youthful and healthy skin.
lecithin in the lipid phase. Next the ethanol is evaporated at A gelling agent optionally may be added to the formula
80 C. The aqueous phase, containing the PLURONIC, and tion. Gelling agents that are suitable for use in the present
lipid phase are heated to 60 C. and mixed together While invention include, but are not limited to, cellulose ethers,
stirring to make a PLURONIC organogel. alginates, polyacrylates, bentonite, gelatin, tragacanth, car
AWater dispersible lecithin such as number 8210 or 8140 bomer 940, polyvinylpyrrolidone, polyvinyl alcohol, and
from Central Soya (Fort Wayne, Ind.) is added to an appro polyoxyethylene/polyoxypropylene block copolymers,
priate amount of deioniZed Water containing the other com 50 some of Which are knoWn as poloxamers. The poloxamer
ponents of the aqueous phase Which is heated to 80 C. (heat compounds are sold collectively under the trademark PLU
labile ingredients may be added at the appropriate tempera RONIC (BASE, Parsippany, N.J PLURONIC F-127 cor
ture during cooling). The lipid phase is heated to 80 C. and responds to poloxamer 407. Other PLURONICS may be
then added to the aqueous phase. Cooling With mechanical used in the present invention.
stirring produces a creamy gel Without the use of solvents, 55 Optionally, a preservative, such as benZyl alcohol, EDTA,
such as organic solvents, Which may be irritating to the skin, vitamin E tocopherol, ascorbyl palmitate, ascorbic acid,
such as facial skin. Example 9 presents a method of making alpha lipoic acid or sorbic acid, can be added to the
and using the Water soluble gel to improve the condition of composition. Other preservatives Well knoWn to those of
chapped hands. ordinary skill in the art can be used in the composition.
Although not Wanting to be bound by the folloWing 60 Agents for improving the aroma of the formulation can
hypothesis, it is believed that the method and composition of optionally be added to the composition. A desired aroma
the present invention cause an increase the Water content of improving agent is honey almond oil (PCAA, Kinghurst,
the skin, perhaps by increasing the ?uid content of the Houston, Tex.). Other aroma improving agents include, but
epidermis and dermis. It is believed that the composition of are not limited to, avocado oil, sesame oil, castor oil, olive
the invention enhances diffusion of moisturiZers, 65 oil, grapeseed oil, clove oil, groundnut oil, corn oil, lemon
surfactants, and emollients into and possibly through the oil, coconut oil, lime oil, haZelnut oil, jojoba oil, carthamus
epidermal and dermal layers of the skin. It is understood that oil and Wheatgerm oil. The oils can be added individually or
 5,945,409
9 10
in combination. It is to be understood that various fragrances A cream Was removed and mixed With lecithin organogel
and assorted ?oral scents may be optionally added to the in a 1:1 ratio to create the experimental cream labeled B.
composition and are commercially available (PCAA, The study Was done in a blind manner, volunteers chose
Houston, Tex.). Stabilizers, antioxidants, preservatives, either the A or B cream and Were unaWare Whether they
humectants, regreasing agents, solvents or auxiliaries can be used control or experimental cream. Treatment continued for
added to improve stability and/or adhesiveness of the for 7 days. Repeated application of the cream after Washing and
mulations. before bedtime Was stressed to the participants. After 3
additional days, the volunteers applied the other cream for 7
In addition, antimicrobial agents can be optionally added days. The skin Was subjectively evaluated for softness and
to the composition of the present invention if required. feel. All 10 subjects reported superior results in promoting
Addition of an antimicrobial agent is desirable When treating 10
healing and moisturiZing the skin. The treated skin appeared
in?ammatory conditions associated With acne, psoriasis or smoother, softer and younger and many cracks disappeared.
eczema.
In addition, 2 of the volunteers Were afflicted with ecZema
The composition of the present invention can be admin Which Was asymptomatic after treatment With the experi
istered topically either once daily or several times per day mental cream.
depending upon the nature and severity of the condition 15
being treated. EXAMPLE 4
It Will be appreciated that other embodiments and uses
Will be apparent to those skilled in the art and that the Application of Composition to the Human Face
invention is not limited to these speci?c illustrative
examples. 20
A 46 year old Woman exhibited Wrinkling of the perior
bital skin at the lateral margin of the orbit. The composition
EXAMPLE 1 Was applied topically to this region 2 to 3 times per day.
Within 10 days the Wrinkled appearance of the skin Was
Lecithin Organogel Composition Prepared With dramatically diminished. This skin appeared fuller and
Pluronic smoother. The Wrinkling of the skin Was greatly reduced
25 With ?ne lines generally less evident.
A preferred composition Was prepared as described
beloW. The lecithin organogel Was prepared by dissolving 20 EXAMPLE 5
g of soy lecithin granules (PCAA, Houston, Tex.) in 20 ml
of isopropyl palmitate (PCAA, Houston, Tex.). The mixture Application of the Composition to the Skin
Was stirred periodically for 24 hours until the soy lecithin 30 Adjacent to Fingernails and Toenails
granules Were dissolved. The PLURONIC gel 20% stock
solution Was prepared by dissolving 16 g of PLURONIC Several human volunteer subjects exhibited dry and
F127 poWder (BASE, Parsippany, N.J.), also called polox cracked skin at the bases of the ?ngernails and in the skin at
amer 407, in 80 ml of puri?ed Water. Potassium sorbate (160 the distal tips of the ?ngernails. They applied the cream for
mg; PCAA, Houston, Tex.) Was added to the PLURONIC 3 to 4 times daily for 3 to 7 days and Within 72 hours
35
gel 20% stock solution as a preservative. This Was placed in observed a reduction in the cracked appearance of the skin.
the refrigerator at about 4 C. for about 24 hours and stirred Cracks that had developed into deep grooves began to
periodically. gradually close. Within 7 days, most of these cracks had
completely disappeared and pain Was greatly abated.
The composition Was prepared by mixing 20 ml of the
lecithin organogel With 2 ml of the honey almond oil 40 EXAMPLE 6
(PCAA, Houston, Tex.) until a smooth mixture Was pre
pared. Honey almond oil Was added for fragrance. Next, 80 Treatment of Hair
ml of the PLURONIC gel 20% stock solution Was mixed in
until a gel formed. A blender Was used for this mixing step The fur of rats Was shaved and various treatments applied,
at room temperature With disinfected equipment. The gel including lecithin organogel With PLURONIC, lecithin
45
Was stored at room temperature. organogel With N-decylmethyl sulfoxide and alpha hydroxy
acids (glycolic or lactic acids partially neutraliZed With
EXAMPLE 2 sodium hydroxide), urea and salicylic acid. The results
shoWed a qualitative increase in the hair shaft diameter. In
Lecithin Organogel Composition Prepared Without addition, regroWth of the hair Was faster after treatment With
Pluronic lecithin organogel containing PLURONIC.
In another embodiment of the present invention, the In vitro treatment of hair With alpha hydroxyacids,
composition described in Example 1 Was prepared using N-decylmethyl sulfoxide, salicylic acid and urea increased
lecithin organogel Without the addition of the PLURONIC hair shaft diameter by about 20% When examined With a
gel 20% stock solution. The ?nal concentration of lecithin micrometer under a microscope.
organogel Was in the range of 2040% by modifying the 55 One embodiment of this application to hair is to use alpha
ratio of lecithin organogel to Water. hydroxy compounds Which have a loW pH (about 1.2),
adjust the pH to a value of about 55 .5 With a base such as
EXAMPLE 3 sodium hydroxide, and apply a 2025% concentration to the
hair overnight. The hair Would be Washed the next morning,
Hand Treatment of Human Subjects 60 thereby enhancing absorption of Water into the hair. The
The lecithin organogel composition (not including result Would be thicker and more luxurious hair.
PLURONIC) Was topically applied in cream form to the skin EXAMPLE 7
of one hand of each of 10 human volunteers (965 years of
age) With a history of dry skin (xerosis) consisting of Preparation of Lecithin Organogel
chapped hands While the other hand received treatment With 65
control creams. These control creams labeled A, consisted Approximately 95% pure lecithin may be dissolved in
of three commercial hand creams. Another portion of each isopropyl palmitate or isopropyl myristate on a Weight basis
 5,945,409
11 12
of 1 g of lecithin per about 0.5 to 1.5 g of isopropyl palmitate Procedure
or isopropyl myristate. The preferred ratio of lecithin to Part 1 Was heated to 70 C. With stirring. Part 2 Was heated
these solvents is about 1 g to about 0.75 g to 1 g. Next
to 75 C. With stirring. Parts 1 and 2 Were combined With
ethanol (98%) may be added While stirring at 80 C. until the
stirring. Part 3 Was added to the batch at 35 C. With stirring.
alcohol is boiled off. Water is then added With stirring at
approximately 20 to 40% With a preferred concentration of
about 30%. EXAMPLE 10

EXAMPLE 8 Lecithin Dissolved in Ethanol Which is Then

10
Evaporated
Lecithin Organogel Prepared With PLURONIC
A penetration enhancer of the present invention is PLU Part 1
RONIC F-127 (BASE, Parsippany, N.] which permits use
of lecithins of lesser purity than those required in formation Deionized Water 38.5%
PL127 20% 13%
of lecithin organogels as taught by Williman et al. PLU 15 Glucosamine/glucosamine 2%
RONIC F-127 is employed at concentrations of about 0.1% sulfate
to 45% in a ratio PLURONIC to lecithin of about 1:05 to Allantoin 1%
1:60. A preferred ?nal concentration of PLURONIC F-127 Ammonium lactate 5%
is 5% to 20% in a ratio of PLURONIC to lecithin of 1:2 to dl-pyroglutamic acid 2%
1:4. Lecithins of concentrations of approximately 5% to Part 2
20
90% are ?rst dissolved in isopropyl palmitate, isopropyl Vanishing cream 7%
myristate and/or 98% ethanol. The addition of four parts of Cholesterol 5%
PLURONIC F-127 (20% solution) to the dissolved lecithin Aloe vera oil 5%
produces a cost effective gel. In addition, Water, carboxy Glycerol 5%
safflower oil 2%
ethyl cellulose, carboxymethyl cellulose, other Borage oil 2%
PLURONICS, and other agents knoWn to one skilled in the 25 Phospholipon 90H 7.5%
art may be used. These mixtures are knoWn PLURONIC ethanol 20 ml
organogels or poloxamer organogels. Part 3

EXAMPLE 9 Retinal palmitate 1%

30 7 dehydrocholesterol 1%
Ascorbyl palmitate 2%
Water Dispersible Lecithin Without Organic Vitamin E tocopherol 1%
Solvent Proanthocyanidin 1%
Nurses, aids and other personnel must Wash their hands
after degloving Which may be as frequent as 4080 times in 35
an 810 hour shift. Three nurses at an intensive care unit at Procedure
a local hospital had a chronic problem With chapping and Part 2 Was heated to 60 C. While stirring, thereby
Were stressed by the possibility of HIV or Step A infection. dissolving the lecithin and evaporating the ethanol. Ethanol
All previous products, Whether purchased over the counter Was added to Part 2 at 80 C. While stirring. After the ethanol
or by prescription, had not successfully treated the chapping. evaporated, part 2 Was added to part 1 While stirring
The gel Was prepared as folloWs. Excellent results Were 40 mechanically. This mixture Was stirred until a gel formed at
evident in 35 days. about 60 C. Fragrance Was optionally added With part 3 at
35 C. to the batch While mechanically stirring.
Part 1 This composition Was applied to the skin of a 54 year old
Lecithin 8120 7.5% 45
male and also to the skin of four females of 49, 20, 12, and
Deionized Water 15% 11 years of age. Each of these subjects complained of dry
DL-pyroglutamic acid 5% skin prior to application of the composition. FolloWing
Urea 2% topical application of the composition, each subject exhib
Glucosamine/glucosamine 2% ited superior moisturiZation of the skin in the treated area.
sulfate
Manganese ascorbate 0.5% 50 This composition is an elegant and ef?cacious moisturiZer
PL127 20% 14% Which has no irritating solvent and may be used on the faces
Panthenyl ethyl ester 1%
Part 2 of children, as Well as adults, With sensitive skin.

Glycerol 5% EXAMPLE 11
Aloe vera oil 3% 55
Almond oil 2%
Vanishing cream (stearyl 8.5 g Comparison of Lecithin Dissolved in Isopropyl
alcohol, steric acid, Polyaxyl Palmitate or Isopropyl Myristate With and Without
40 stearate) PLURONIC
Squalene 2%
Part 3 60

Retinal palmitate 10,000 units/gm: 1% Composition 1 Composition 2

7 dehydrocholesterol 1,000 units/gm 0.1%
Part 1
Ascorby paimitate 2 ml 2%
Vitamin E tocopherol 1 ml 1%
Proanthocyanidin 1 ml 1% 65 Deionized Water 53% PL127 20% 53%
Ammonium lactate 5% Ammonium lactate 5%
Citric acid 5% Citric acid 5%
 5,945,409
14
-continued 5. The method of claim 1, further comprising
N-decylmethyl sulfoxide.
Composition 1 Composition 2 6. The method of claim 1, further comprising composi
Part 2 tions selected from the group consisting of antimicrobial,
antibacterial, antifungal, antiprotozoal, and antiviral agents.
Lecithin granules 30% Lecithin granules dissolved 30% 7. The method of claim 1, further comprising glucosamine
dissolved in IPM or IPP in IPM or IPP
or glucosamine sulfate.
Glycerol 5% Glycerol 5%
Capric/caprylic 2% Capric/caprylic 2% 8. The method of claim 1, further comprising molecules
triglycerides triglycerides selected from the group consisting of alpha hydroxy
10 compounds, glycolic acid, citric acid, and lactic acid.
9. The method of claim 1, further comprising molecules
Procedure for Making Composition 1 selected from the group consisting of glycerol, urea,
An equal weight of IPM was dissolved with lecithin ceramides, squalene, elastin, salicylic acid, dimethicone,
granules and allowed to stand overnight. Addition of part 2 lanolin, chondroitin sulfate, hyaluronic acid, collagen, and
to part 1 produced a 2-phase system which did not disperse 15 collagen fragments.
with mixing at 60 C. 10. The method of claim 1, wherein the composition is in
Procedure for Making Composition 2 a form selected from the group consisting of lotions, salves,
Part 1 was heated to 60 C. Part 2 was heated to 60 and creams, liposomes, sprays, micelles, and gels.
added to part 1 with mechanical mixing. The mixture was 11. A method of treating psoriasis comprising the step of
allowed to cool. 20 topically applying to the skin of the human or animal the
Asimilar area on either arm was chosen to test the ef?cacy composition of claim 1.
of the two compositions which were applied three times a 12. A method of treating psoriasis comprising the step of
day for ?ve minutes and then washed off with soap. The topically applying to the skin of the human or animal the
moisture content of the outer stratum corneum may be
composition of claim 2.
evaluated subjectively in that a rough, ?aky appearance is
25 13. A method of treating eczema comprising the step of
obvious and a white dust like material is evident upon
topically applying to the skin of the human or animal the
scratching lightly with a ?nger tip. These impressions are
composition of claim 1.
clinically valuable, but very dif?cult to quantify. 14. A method of treating eczema comprising the step of
D-Squame discs (CuDerm Corp., Dallas Tex.) were used topically applying to the skin of the human or animal the
to quantify dry skin and objectively evaluate relative effi 30 composition of claim 2.
cacy of moisturizers. The disc is applied ?rmly to a similar 15. The method of claim 1, further comprising molecules
area of each arm, pressed ?rmly, and then transferred to a selected from the group consisting of elastin, elastin
black card for evaluation. Normal skin produces a few areas
of small clumps of cells or even a ?ne even single layer. Very
fragments, elastin-glycolic acid, collagen, collagen
fragments, yeast extracts, skin respiratory factor,
dry skin produces heavy amounts of scaling. 35 glucosamine, glucosamine sulfate, hyaluronic acid,
In order to simulate the work conditions which cause hyaluronate, chondroitin sulfate, cholic acid, deoxycholic
chapping the compositions were removed 15 minutes after acid, ginseng extract, aloe vera powder, aloe vera oil, RNA
application by washing with soap and water. and DNA fragments, ascorbyl palmitate, ascorbic acid, reti
After 24 hours the PLO moisturizer was rated 3 on a 15 nal palmitate, 7-dehydroxycholesterol, vitamin E
scale, with 5 being the heaviest clumping. Composition 1 40 tocopherol, vitamin E lineolate, panthenyl ethyl ester, glyc
was a 45 and remained such for 5 days. Over the course of erol ceramides, glycogen, DL-pyroglutamic acid, urea,
the next 4 days, the PLO composition produced less scaling sodium lactate, lactate, glycerin, sorbitol, oils of borage,
25 and was softer to the touch. The ?nger tip could not evening primrose, black currant, almond and cannola, van
produce the white powder as was possible before the trial. ishing cream, cholesterol, ?avenoids, witch hazel,
The production of the PLO allowed an effective delivery 45 camomile, parsley, hibiscus, capric and caprylic
of the active ingredients which produced the moisturization. triglycerides, amino acids, allantoin, sodium, calcium,
Lower grade lecithin dissolved in an organic solvent has potassium, phosphate, chloride, sodium lactate, alpha
poor moisturizing properties. hydroxy acids, cocoa butter, coconut oil, jojoba oil, saf
It should be understood, of course, that the foregoing ?ower oil, wheat germ oil, sesame oil, selachyl alcohol,
relates only to preferred embodiments of the present inven shark oil, cerebrosides, proanthocyanidin, farnestol,
tion and that numerous modi?cations or alterations may be candelellila, carnuba wax, vitamin E nicotinate, manganese
made therein without departing from the spirit and scope of ascorbate, zinc, oleyl alcohol, polysorbate 80, spermaceti,
the invention. glycerol monostearate, beeswax, silicone oil, paraf?n wax,
I claim: ozokerit E, and PEG 75 lanolin.
1. A method of treating keratinous tissue of a human or 55 16. The method of claim 2, further comprising molecules
animal comprising the step of topically applying to the selected from the group consisting of elastin, elastin
keratinous tissue a composition comprising water dispers fragments, elastin-glycolic acid, collagen, collagen
ible lecithin. fragments, yeast extracts, skin respiratory factor,
2. A method of treating keratinous tissue of a human or glucosamine, glucosamine sulfate, hyaluronic acid,
animal comprising the step of topically applying to the 60 hyaluronate, chondroitin sulfate, cholic acid, deoxycholic
keratinous tissue a composition comprising lecithin, a acid, ginseng extract, aloe vera powder, aloe vera oil, RNA
solvent, and water. and DNA fragments, ascorbyl palmitate, ascorbic acid, reti
3. The method of claim 2, wherein the solvent is isopropyl nal palmitate, 7-dehydroxycholesterol, vitamin E
palmitate, isopropyl myristate, ethyl myristate, tocopherol, vitamin E lineolate, panthenyl ethyl ester, glyc
2-octyldodecanol or ethanol. 65 erol ceramides, glycogen, DL-pyroglutamic acid, urea,
4. The method of claim 1, further comprising poloxamer sodium lactate, lactate, glycerin, sorbitol, oils of borage,
407. evening primrose, black currant, almond and cannola, van
 5,945,409
15 16
ishing cream, cholesterol, ?avenoids, Witch hazel, 19. The method of claim 1, Wherein the composition
camomile, parsley, hibiscus, capric and caprylic further comprises Water, pyroglutamic acid, urea,
triglycerides, amino acids, allantoin, sodium, calcium, glucosamine, glucosamine sulfate, manganese ascorbate,
potassium, phosphate, chloride, sodium lactate, alpha poloXamer, panthenyl ethyl ester, glycerol, aloe vera oil,
hydroXy acids, cocoa butter, coconut oil, jojoba oil, saf almond oil, vanishing cream, squalene, retinal palmitate,
?oWer oil, Wheat germ oil, sesame oil, selachyl alcohol, dehydrocholesterol, ascorbyl palmitate, vitamin E toco
shark oil, cerebrosides, proanthocyanidin, farnestol, pherol and proanthocyanidin.
candelellila, carnuba Wax, vitamin E nicotinate, manganese 20. The method of claim 2, Wherein the solvent is ethanol,
ascorbate, Zinc, oleyl alcohol, polysorbate 80, spermaceti, and the composition further comprises poloXamer,
glycerol monostearate, beesWaX, silicone oil, paraffin Wax, glucosamine, glucosamine sulfate, allantoin, ammonium
oZokerit E, and PEG 75 lanolin.
17. Amethod of treating ichthyosis comprising the step of lactate, pyroglutamic acid, vanishing cream, cholesterol,
topically applying to the skin of the human or animal the aloe vera oil, glycerol, safflower oil, borage oil, retinal
composition of claim 1. palmitate, dehydrocholesterol, ascorbyl palmitate, vitamin E
18. Amethod of treating ichthyosis comprising the step of 15 tocopherol and proanthocyanidin.
topically applying to the skin of the human or animal the
composition of claim 2.