Note: Descriptions are shown in the official language in which they were submitted.
CA 02325337 2000-11-09
USE OF LIVE YEAST CELL DERIVATIVE TO TREAT BED SORE PRESSURE
ULCERS
FIELD OF THE INVENTION
The present invention relates to topical treatments for
pressure ulcers also known commonly as bed sores, which most
commonly occur in non-ambulatory, bed ridden medical
patients, or in patients with limited mobility.
BACKGROUND OF THE INVENTION
Pressure ulcers, commonly known as bedsores, are a
vascular problem caused by a patient's constant weight
bearing at a site due to inactivity. The mechanism is
understood to be related to decreased blood flow through
capillaries at the site; this results in deficient
oxygenation of cells in the local area, which causes
morbidity.
Pressure ulcers are wounds that occur as a result of
prolonged pressure due to body weight against a surface such
as a bed or wheel chair. Pressure ulcers, occur where a
bony protuberance concentrates a person's weight against the
skin and its underlying support. This causes vascular
constriction which limits nutrient and oxygen blood flow in
the area of the wound, so that the wound forms and worsens.
The incidence of pressure ulcers is high especially
among certain risk groups including elderly patients
admitted to hospitals for femoral fracture (66% incidence),
critical care patients (33% incidence), and residents of
skilled care facilities and nursing homes (up to 23%
incidence). A study of acute care facilities reported an
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CA 02325337 2008-07-07
incidence of 9.2% while one study of quadriplegic patients
revealed a prevalence of 60%.
Several adjunctive therapies have been used in attempts
to enhance pressure ulcer healing. Among these has been the
application of a variety of topical agents. These have,
included the topical use of zinc oxide (such as "DesitinTM"
OTC ointment). Vitamin A and vitamin D treatments such as
"A&D" OTC ointments, a product known as"GranulexT"'", and
petrolatum and lanolin in an emulsion are also prior art
topical treatments. These have not proven effective in
promoting healing of pressure ulcers.
The prior art also includes reference to the use of
live yeast cell derivative (LYCD) to treat burn victims. A
study by Kaplan, "Acceleration of Wound Healing By A Live
Yeast Cell Derivative", Arch Surg Vol. 119, Sept. 1984 pp.
1005-1008 showed that a concentration of 2,000 units/g of
LYCD in an ointment base was effective in accelerating burn
wound healing.
However, it must be noted that burn damage is
qualitatively different from that of pressure ulcers. Cells
are damaged by burns through de-naturing of the cell's
protein. In contrast, pressure ulcers are caused by a local
vascular deficiency.
In fact, the United States Dept. of Health and Human
Services stated in " Treatment of Pressure Ulcers" Clinical
Practice Guideline, Number 15, HHS, AH CPR Publication No.
95-0652, Dated December, 1994, at page 56 that yeast
extracts, such as live yeast cell derivative (LYCD), are not
recommended for treatment of pressure ulcers because of
limited efficacy. Therefore, the use of live yeast cell
derivative (LYCD) has not been previously proved to be
effective in treatment of pressure ulcers.
U.S. Patent No.5,714,169 of Levin describes treating
wounds, including pressure ulcers with topically applied
medicinal composition in combination with a live yeast cell
derivative (LYCD). However there is no proof that the live
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CA 02325337 2000-11-09
yeast cell derivative (LYCD) is anything but incidental,
since medicinal recombinant growth factors are known as
wound healing agents.
Moreover, US Patent No. 6,143,321 of Needham describes
liposomes as medicinal formulations designed to promote the
effectiveness of poorly water soluble components. In a
liposome, an outer lipid layer, such as a phospholipid,
surrounds and entraps a water soluble component therein.
Furthermore, US patent no. 5,776,441 of Scancarella,
assigned to Avon Products, Inc., describes a lip balm
composition of live yeast cell derivative LYCD in
petrolatum. However, Scancarella '441 describes and gives
examples of liquid or powdered live yeast cell derivative
(LYCD), neither of which are liposome encapsulated.
US patent no. 5,874,479 of Martin, assigned to Warner
Lambert, describes a wound composition that mentions
treating decubitus ulcers among many types of wounds.
However, the studies it conducted were treatment of incision
wounds on mice, not treatment of humans with pressure
ulcers. In Table A of Martin '479, there is a comparison of
four formulations, namely, 1) PREPARATION H , 2) petrolatum
with LYCD, shark oil, and a mixture of pyruvate, vitamin E
and chicken fat, 3) petrolatum with LYCD and shark oil and
4) petrolatum only.
However, Martin '479 does not describe a method of
treating pressure ulcers with a composition comprising
petrolatum with liposome encapsulated live yeast cell
derivative (LYCD )and shark liver oil.
Other wound healing treatment regimens are disclosed in
W. Goodson et al. "Augentation of Some Aspects of Wound
Healing By a 'Skin Respiratory Factor "', J Surg Res 1976
81:125-129, J. Niinikoski "The Effect of Blood and Oxygen
Supply of the Biochemistry of Repair" (TK Hunt ed.) Wound
Healing and Wound Infection: Theory and Surgical Practice,
1980 Appleton-Century-Crofts, NY, and Treatment of Pressure
Ulcers. Clinical Practice Guideline No. 15, US Dept. of
3
CA 02325337 2001-02-13
4
Health and Human Services, AHCPR Pub. No. 95-0652, Maibacvh, HF, Rovee
DT: Epidermal Wound Healinq; Mosby, St. Louis, MO, 1972, Brody, HJ:
Chemical Peeling; Mosby, St. Louis, MO 1992:27-31; and Ghadially, et al.,
"Effects of Petrolatum on Stratum Corneum Structure and Function,". J.
AM.ACAD.DERM. 192:26;387-96 (VA Hospital Study NIH Grant).
Also known are Pulgiese, PT,et.al., "Some Biological Actions of
Alkylglycerols from Shark Liver Oil," J. Ahern Complement Medicine. '98 4
(1):87-89, Loftssson, T., Petersen DS, " Unsaturated Glycerol Monoethers as
Novel Skin Protection Enhancers," Dept. of Pharmacy, Univ. of Iceland,
Reykjavik Pharmzie ' 97 Jun:52(6);463-5.
Live yeast cell derivative (LYCD) has been used to aid in healing and to
reduce patient recovery time and discomfort after facial peeling, which is the
controlled wounding of skin. It is believed that the live yeast cell
derivative
(LYCD) re-generates facial peeled skin with greater collagen levels and
improved cosmetic appearance. Such skin facial wounds which have been
effectively treated with live yeast cell derivative (LYCD) include those
caused by
dermabrasion, chemical burns from application of trichloroacetic acid, of
thermal
burns from a laser. The live yeast cell derivative (LYCD) supports natural
homeostatic regulators found in skin cells and contains tissue respiratory
factor
(TRF) that increases cellular respiration. See footnotes 3,4,5.
However it is not known to provide a topical composition for treatment of
pressure ulcers (bed sores) with biologically active yeast extract, including
live
yeast cell derivative (LYCD).
EMBODIMENTS OF THE INVENTION
It is therefore a feature of one embodiment of the present invention to
promote prevention and treatment of pressure ulcers.
It is also a feature of another embodiment of the present invention to
promote vascularization of capillary blood vessels to counteract the
development of pressure ulcers.
It is yet a feature of another embodiment of the present invention to
CA 02325337 2001-02-13
provide a skin protectant ointment containing live yeast cell derivative
(LYCD)
useful in the treatment of pressure ulcers.
It is a further feature of another embodiment of the present invention to
make the previously ineffective use of live yeast cell derivative (LYCD)
effective
5 in treating pressure ulcers.
It is also a feature of another embodiment of the present invention to
minimize the risk of infection, patient discomfort and recovery times when
treating pressure ulcers.
It is also a feature of another embodiment of the present invention to
provide treatment modalities for all of the various stages of pressure ulcers.
It is also a feature of one embodiment of the present invention to promote
collagen synthesis in fibroblasts by increasing oxygen, thereby, promoting
cellular respiration, for the healing of pressure ulcers.
It is also a feature of one embodiment of the present invention to promote
acceleration of re-epithelialization, angiogenesis, and pain reduction in
patients
with pressure ulcers.
SUMMARY OF THE INVENTION
The present invention relates to a topical composition for treating
pressure ulcer bed sores and related skin disorders including alleviating bed
sores of various degrees, said topical composition comprising a compound
including liposome encapsulated live yeast cell derivative (LYCD), said
composition being provided in a substantially anydrous pharmaceutically
acceptable base.
In a preferred embodiment of the invention, the live yeast cell derivative
(LYCD) is provided in an amount of about 200 to about 600 biologically active
units per 100 grams of the composition, and the composition further comprises
a
skin enhancing penetration solvent.
In a more preferred embodiment, the composition comprises the following
components, listed by percentage of the total composition.
CA 02325337 2001-02-13
5A
Ingredient Ran4e (%w/w)
Petrolatum 10 - 99.5%
Live Yeast Cell
Derivative (LYCD) at least 200 biologically active units per 100
grams of the composition
In yet another preferred embodiment, the composition comprises the
following components, listed by percentage of the total composition:
In req dient Ranae (%w/w)
Petrolatum 87.5%
Live Yeast Cell
Derivative (LYCD) at least 600 biologically active units per 100
grams of the composition
The present invention relates, in another embodiment to a method for
treating patients prone to bed sore problems and related skin disorders,
including alleviating bed sores of various degrees.
The above compositions and methods of the present invention includes
the use of a skin protectant topically applied ointment containing an
effective
amount of live yeast cell derivative (LYCD), preferably as a lipsome
encapsulated composition. The ointment of the present invention is effective
by
virtue of its skin penetration abilities in the treatment of bed sore
CA 02325337 2000-11-09
pressure ulcers, as shown in clinical trials of the use of
the subject matter of the present invention.
This topically applied ointment is used by
dermatologists, plastic surgeons and cosmetic surgeons as
an adjunct therapy to protect the wound and to promote
healing. In its original use, it has been found to minimize
the risk of infection, patient discomfort and recovery
times. Clinical trials have shown similar results in the
treatment of pressure ulcers (bed sores), especially in non-
ambulatory patients.
An ointment of the present invention was shown in the
clinical trials to be therapeutically effective in the
prevention and treatment of inflammation in Stage I and
Stage II pressure ulcers. In one clinical trial, an
ointment of the present invention either resolved pressure
ulcers by returning affected skin to pre-wound status,
prevented further development, or markedly improved the
pressure ulcer wounds treated during a five week clinical
study.
Unlike the previous ineffective attempts to use live
yeast cell derivative (LYCD) to treat pressure ulcers, the
formulation of the present invention is effective because it
enhances deep dermal penetration of the live yeast cell
derivative (LYCD) to the capillaries and wounded tissues.
The deep dermal penetration occurs for three reasons.
First, the live yeast cell derivative (LYCD) is preferably
incorporated as a liposome encapsulated composition, which
enhances deep skin penetration. Second, a pharmacological
solvent, such as shark liver oil, with its component mono-
ethers, enhances skin penetration. Third, the preferably
anhydrous base for the liquid live yeast cell derivative
component formed with an occlusive agent, such as petrolatum
provides an occlusion that keeps air out and opens skin
pores up, causing sweating and resultant absorption of the
live yeast cell derivative (LYCD) deep within the dermis.
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It is further noted that in an alternate embodiment the
liposome encapsulated live yeast cell derivative may be
provided in a petrolatum base, without the shark liver oil
as a penetrating enhancing solvent, since petrolatum is also
a skin penetration enhancer by itself, as well as an
occlusive agent.
Moreover, in an alternate embodiment, the liposome
encapsulated live yeast cell derivative may be provided in a
petrolatum base, but with one or more other penetrating
enhancing solvents, such as oleic acid, trihydroxy
compounds, ethoxydiglycol, propylene gylcol, polyethylene
glycol, terpenes, trichloroethanol, urea, butylene glycol,
alcohols, dimethyl formamide, dimethyl sulfoxide (DMSO), 1
dodecylazacycloheptan-2-one, methyidecyl sulfoxide (DMS) and
N-methyl pyrrolidone.
Therefore, the required components of the formulation
of the present invention include preferably petrolatum, as a
vehicle for the LYCD treatment composition to enhance
occlusion, shark liver oil to enhance penetration and
liposome encapsulation of the live yeast cell derivative
(LYCD), which is provided in biologically active units of
yeast.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention, a method is
provided for the treatment of pressure ulcers, also known as
bedsores, as well as excoriation and treatment of the peri-
wound area. The method includes the topical application of
an ointment of the present invention containing an effective
amount of biologically active live yeast cell derivative
(LYCD) encapsulated liposome as an adjunctive therapy as
appropriate to the particular treatment modalities of the
various stages of pressure ulcers (stage I through IV) as
defined by the National Pressure Ulcer Advisory Panel
Consensus Development Conference (NPUAP, 1989).
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In accordance with the present invention the method for
treating and curing pressure ulcers includes wound cleaning
at least once a day and preferably as often as required
during a day, by topical application of an ointment
containing an effective amount of biologically active live
yeast cell derivative,(LYCD), preferably an ointment
prepared with a petrolatum base or similar water resistant
carrier material for the live yeast cell derivative (LYCD),
which is preferably a liposome encapsulated LYCD compo.sition
and a pharmaceutically acceptable carrier, the applications
of ointment to completely cover the pressure ulcer and
surrounding area of skin, and then preferably applying a
clean dry dressing. In accordance with the invention the
treatment method is continued for at least about two weeks
or longer, if required.
The biologically active live yeast cell derivative
(LYCD) used in the present invention is quantified as a
quantity of biologically active units, of an amount of about
200 more biologically active units per applied dose, such as
for example, 600 biologically active units, or more.
Biologically active live yeast cell derivative (LYCD)
typically is measured as a Warburg assay at not less than 8
biologically active units per milligram of yeast extract. To
obtain 600 biologically active units, it is provided from
raw yeast extract in an amount of about 600 biologically
active units per 100 grams of finished product.
The biologically active live yeast cell derivative (LYCD) is
commercially available as an extract of varying amounts of
active live yeast cell derivative in numerous forms,
including as a liquid, a powder, a concentrate, a gel, a
paste or as a liposome encapsulated LYCD.
Although all of these forms are efficacious, the
preferable form is an extract encapsulated within a
liposome.
The carriers for the liquid or concentrates include
water, alcohols, glycols, and preserved serums. The powders
8
CA 02325337 2008-07-07
have extenders such as, but not limited to, dextrose or
starches. The liposomes can be of any suitable form, such as
for example, with phospolipids.
Among commercially available yeast extract is product
no. 8013-01-2 of Red Star Yeast and Products of Milwaukee,
Wisconsin, which yeast extract is a spray dried yeast
extract fraction.
According to the National Formulary of the United
States Pharmacopeia(1998), yeast extract is a peptone-like
derivative of yeast cells (Saccharomyces) which is water-
soluble.
In a preferred embodiment, the over the-counter (OTC)
skin protectant ointment of the present invention is
predominately petrolatum U.S.P. as a base carrier for live
yeast cell derivative (LYCD) with a pharmaceutically
acceptable delivery topical vehicle, which may also contain
the following optional ingredients: yucca extract,
ceramides, shark liver oil, Vitamin E (tocopherol), benzyl
alcohol, and green tea extract.
Each of these components has been shown in the medical
literature to have effects that promote healing by a variety
of mechanisms.
The yeast extract, which is the source of the live cell
derivative (LYCD),of various biological activity, has been
reported to promote collagen synthesis in fibroblasts by
increasing oxygen, which may be important for promoting
cellular respiration and for the healing of pressure ulcers.
See footnotes 3,4,5. Other related effects of live yeast
cell derivative (LYCD) include the acceleration of re-
epithelialization, angiogenesis, and pain reduction.
Other ingredients that may be included in the topical
ointment of the invention include yeast extract having a
high vitamin B content and which is characterized by a
liposomal delivery system. Further ingredients include yucca
extract, containing complex polysaccharides, which increases
moisturization, which may be important in the treatment of
9
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pressure ulcers, as well as promoting a soothing ingredient
much like aloe vera; ceramides, which normalize barrier
function by regulating fluid levels; and to enhance
moisturization, wherein they are the mortars in the brick
and mortar model of the stratum corneum; a skin penetration
enhancing solvent such as shark liver oil, containing
unsaturated glycerol monoethers, 6, and Vitamin E, which is
a well-known antioxidant, which moderates the inflammation
reaction resulting in accelerated wound recovery 7, 8.
Furthermore, benzyl alcohol is often used as an anti-
microbial in ingestables and injectables 10, 11. It has
topical anesthetic properties. It is also very mild, as
illustrated by its use in intravaginal preparations. Green
tea extract is also used. It is a known antioxidant and
also a source of catechins and polyphenols. It is also a
free radical scavenger and a source of tannin.
To increase shelf life, mineral oil and lanolin
alcohol, such as provided in the AMERCHOLTM L-101 product,
stabilize the formulation.
Clinical studies, which have been conducted with
statistically significant results, reveal that the method of
the present invention including the application of the
topical ointment of the present invention, is effective in
treating and reducing the effects of pressure ulcers (bed
sores) in non ambulatory nursing and adult home patients.
The resultant topical ointment is a comfortable
delivery vehicle, which delivers an effective amount therein
of yeast of extract, and related components to the skin in a
manner which promotes penetration and vascularization of
capillaries and treatment of pressure ulcers.
The following examples illustrate typical topically
applied skin care products, which can be prepared using
conventional procedures, from the following ingredients with
ranges of acceptable percentages shown by weight, and
typical preferred percentage by weight showns
CA 02325337 2000-11-09
Preferably the carrier for the active live yeast cell
derivative (LYCD) component is an anhydrous base, such as
for example, petrolatum.
The live yeast cell derivative (LYCD) is quantified in
the following Formulations 1 through 6 as biologically
active units per 100 grams of finished product.
The formulations are illustrative only:
Formulation #1:
Ingredient Ranqe(%w/w) Preferred (%w/w)
Petrolatum 10-99.5 50-99.5
Live Yeast Cell
Derivative (LYCD) at least 200 about 600
Formulation # 2:
In the aforementioned clinical trials, substantial
improvement occurred with the preferred embodiment of the
following Formulation #2, which quantifies the live yeast
cell derivative (LYCD) as biologically active units per loo
grams of finished product. The reference to Amerchol L-101
refers to a commercial mixture of mineral oil and lanolin
alcohol.
Ingredient(% w/w) Range ($wjw) Preferred
Petrolatum 10-99 88.95
Amerchol L-101 0.1-30 7
Ceramides 0.0-5 0.1
Shark Liver Oil 0.1-25 0.25
Yucca Extract 0.0-50 1.0
Tocopherol (Vitamin E) 0.0-10 0.1
Benzyl Alcohol 0.0-5.0 1.0
Green Tea Extract 0.0-10 0.1
LYCD (Liposome encapsulated)
at least 200 about 600
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Other formulations with anhydrous carriers include:
Formulation 13:
Ingredient Range(%w,(w) Preferred (%wlw)
Petrolatum 10-99.5 50-99.5
(preferred 50-99.5)
Mineral Oil 0.0-99.5 7
Lanolin Alcohol 0.0-10 1
Yucca Glauca Extract 0.0-50 1
Shark Liver Oil 0.0-5. 0.25
Vitamin E 0.0-10.0 0.1
Benzyl Alcohol 0.0-5.0 1.0
Green Tea Extract 0.0-10.0 0.1
Ceramides 0.0-5.0 0.1
Phospholipids 0.0-20.0 1.25
Live Yeast Cell
Derivative (LYCD) at least 200 about 600
The LYCD is expressed as biologically active units per
100 grams of finished product.
Formulation 1 4:
Ingredient Range(%wfw) Preferred (%w/w)
Petrolatum 10-90.0 50-99.5
Mineral Oil 0.0-70.0 10.0
Paraffin Wax 0.0-50.0 5.0
Lanolin Alcohol 0.0-20.0 1.0
Yucca Glauca Extract 0.0-70.0 2.0
Aloe Vera Gel 0.0-70.0 1.0
Shark Liver Oil 0.0-25.0 0.25
Green Tea Extract 0.0-70.0 0.25
Benzyl Alcohol 0.0-10.0 1.0
Vitamin E 0.0-25.0 0.1
Vitamin A 0.0-5.0 0.2
Vitamin D 0.0-1.0 0.2
Ceramides 0.0-5.0 0.25
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Soybean Extract 0.0-25 0.25
Corn Oil 0.0-25 0.25
Phospholipids 0.0-20.0 1.25
Live Yeast Cell
Derivative (LYCD) at least 200 about 600
The LYCD is expressed as biologically active units per
100 grams of biologically active finished product.
In the above noted formulation, Vitamin D is provided
at about 20,000 International units (IU) per gram. Vitamin
A is provided at about 1,000,000 International units (IU)
per gram. Vitamin E is provided at about 1.1 million
International units (IU) per gram, as Tocopheryl Acetate.
Formulation 1 5:
Ingredient Ranqe(%wJwl Preferred (%wlw)
Petrolatum 10-99.5 50-99.5
Mineral Oil 0.0 -5.0 6.5
Lanolin Alcohol 0.0-5.0 0.35
Yucca Glauca Extract 0.0-10.0 1.0
Shark Liver Oil 0.0-10.0 0.30
Green Tea Extract 0.0-25.0 0.1
Benzyl Alcohol 0.0-10.0 0.5
Vitamin E 0.0-10.0 0.1
Ceramides 0.0-5.0 0.1
Hydrogenated Vegetable
Oil 0.0 -99.5 51.05
Phospholipids 0.0-20.0 1.25
Live Yeast Cell
Derivative (LYCD) at least 200 about 600
The LYCD is expressed as biologically active units per
100 grams of biologically active finished product.
In the above formulation, Vitamin E is provided at
about 1.1 million International units (IU) per gram.
13
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While the aforementioned formulations #1 through #5 are
preferably in an anhydrous carrier, such as petrolatum, for
example, it has also been found that a typical cream version
of the topical applied ointment in an aqueous base can be
effective in treating early Stage I pressure ulcers, before
the pressure ulcers bed sores advance to Stage II pressure
ulcers. The following formulation is in an aqueous cream
base.
Formulation # 6:
Inctredient Preferred Rw/w)
Water balance of composition
Ca rbome rTM 0.3
Glycerin 2.0
Methylparaben 0.2
Yucca Extract 1.0
Triethanolamine 0.6
Shark Liver Oil 0.1
Green Tea Extract 0.01
Benzyl alcohol 1.0
Imidazolidinyl Urea 0.3
Vitamin E 0.1
Emulsifying Wax 6.0
PPG-2 Myristyl Ether Propionate 3.5
Ceramides 0.1
Squalane 3.0
White wax 1.0
Dimethicone 1.0
Propylparaben 0.1
Live Yeast Cell from about 200 biologically
Derivative (LYCD) active units per 100 grams
(liposome encapsulated) finished product
The present invention therefore comprises a method for
the prevention and/or treatment of pressure ulcers
(bedsores) and related skin disorders with the compositions
of the present invention.
14
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The method comprises the steps of the topical application of
suitable compositions containing live yeast cell derivative
(LYCD), preferably liposome encapsulated in a suitable base,
such as petrolatum which helps occlusion to increase
penetration of the live yeast cell derivative (LYCD); which
also helps penetration to the wound site in the dermis.
Penetration is also enhanced by the addition of a
pharmacological skin penetration enhancing solvent, such as
shark liver oil, with its component monoethers.
In general, the treatment composition suitable for use
in accordance with the invention containing live yeast cell
derivative (LYCD), may be applied in any dermatological
acceptable vehicle such as a gel, lotion, cream, ointment or
pad applied formulation, which may or may not be emulsified
and may contain ingredients to improve, modify, or stabilize
the formulation physically or cosmetically. Other suitable
formulations will be apparent to those skilled in the art.
However, it has been found that water based cream
formulations are primarily only effective in treating early
Stage I pressure ulcers, so anhydrous bases, such as
petrolatum, are preferred.
The treatment compositions of the invention improves
the fluid and homeostatic regulation of the skin and tissues
to which it is applied, preferably by frequent periodical
application over an extended period of time without undue
irritation to the skin or any other side effects.
Generally, the topical applications are applied periodically
such as one or two times per day.
EXAMPLES
The preferred embodiment of Formulation no. 2 above
noted was used in the following clinical studies, which
disclose the efficacy thereof in treating pressure ulcers on
human patients.
Example 1:
CA 02325337 2000-11-09
The use of petrolatum was compared to the ointment of
the present invention in the Treatment of Pressure Ulcers,
in a study by Kuflik, A., Stillo J., Sanders, D., Roland,
P.T., Sweeney, O.T., and Lemke, P. dated November 19, 1999.
The Formulation No. 2 noted above was a new topically
applied, non-prescription medication that was introduced for
re-epithelization of ulcers and erosions of the skin. It
was found that the formulation of the present invention
combines the nurturing and barrier effect of petrolatum with
several other wound healing ingredients.
The object of this study was to compare therapeutic
effects of the formulation No. 2 noted above against
petrolatum by itself as an active ingredient in treating
pressure ulcers of shallow depth (Stage I & II). It is
noted that petrolatum is the anhydrous base ointment
component in the preferred embodiment of the formulation of
the present invention.
A six-weeks randomized, double-blinded study was
performed on twenty patients with Stage I or Stage II
ulcers. These patients received either Formulation Number 2
of the present invention in an Ointment or petrolatum, which
served as a control.
The results showed complete resolution in a majority of
pressure ulcers after a few weeks while only 1/3 of the
pressure ulcers being treated with petrolatum resolved in
the same period of time.
It was therefore concluded that preliminary results
showed that the ointment of the present invention, as in
Formulation No. 2, is a safe and effective treatment for
Stage I & II pressure ulcers.
Previous treatments for pressure ulcers have included
various topical medications, such as creams, ointments and
hydrocolloid dressings; encouragement for movement; and
cessation of all potentially confounding conditions that
could perpetuate the ulcer. Topically applied medications
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CA 02325337 2000-11-09
include a variety of ingredients that fit into both
prescription and non-prescription categories.
In this clinical study there was compared the
therapeutic effectiveness of the ointment of the present
invention, as a topically applied preparation with a novel
combination of ingredients (see below), against its base
component petrolatum in a scientifically controlled,
randomized, double-blinded, control study.
The study consequently considered the ointment of the
present invention as part of a regimen for treatment of
other types of wounds such as Stage I & Stage II Pressure
Ulcers.
The ingredients in the Formulation No. 2 ointment and
their proposed pharmacological actions include: petrolatum,
which helps control water loss from damaged skin by
providing an occlusive protective layer while promoting
normal skin barrier recovery (See footnote 9); liposome
encapsulated live yeast cell derivative (LYCD) which
promotes collagen synthesis through increased tissue
oxygenation and cellular respiration,(see footnotes 3, 4, 5)
shark liver oil which assists in skin penetration of other
ingredients,(see footnote 6); catechins in green tea extract
and vitamin E, which are free radical antioxidants and
moderators of inflammation; benzyl alcohol, which has
antimicrobial and local anesthetic properties(see footnotes
10, 11); ceramides, which are normal components of the
stratum corneum, where they form a barrier to control
moisture loss from the skin, and yucca extract which is used
for its skin moisturizing properties.
Two separate study groups totaling twenty patients were
conducted. Patients with Stage I or Stage II pressure
ulcers were assigned twice daily (BID) treatment with
formulation number 2 of the present invention, or with
petrolatum by itself as an active ingredient. No other
treatments were used.
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The dispensing tubes containing formulation number 2
noted above, or petrolatum, were randomly numbered and their
contents blinded from the patients, physicians and nursing
staffs.
Patients with pressure ulcers having complex underlying
etiologies such as venous stasis and severe diabetes were
excluded from the study. Pressure ulcers were assessed for
stage, size, erythema, and tenderness at the beginning and
end of the study. Patients were monitored for any adverse
effects, such as hypersensitivity, rash, or itching. Before
and after photographs were taken of the pressure ulcers, the
attending physicians were allowed to terminate patients from
the study.
Nineteen patients having either Stage 1 or Stage II
Pressure Ulcers were entered into this study. Eighteen out
of nineteen patients had one ulcer and one had two ulcers.
These nineteen patients were randomly placed in either the
Group being treated with Formulation No. 2 of the present
invention or the Petrolatum Group.
As noted in Table I here, ten patients totaling eleven
ulcers were in the Group being treated with Formulation No.
2 of the present invention. Eight patients totaling nine
ulcers finished the study. Two patients out of ten did not
finish the study. One patient with a Stage I Ulcer was
terminated because of medical conditions and the other with
a Stage II Ulcer was discontinued because of non-improvement
without deterioration. Nine of the remaining ulcers out of
nine treated with the Formulation No. 2 of the present
invention showed some level of improvement.
With respect to Stage I Pressure Ulcers: five of the
nine pressure ulcers in this group were Stage I. Four out
of five Stage I Ulcers were resolved by the end of the
study. One out of five Stage I Ulcers was improved.
Four of the nine pressure ulcers were Stage II. One of
the four Stage II Ulcers was resolved by the end of the
18
CA 02325337 2000-11-09
study. Three of the four Stage II Ulcers were improved by
the end of the study.
With respect to the Petrolatum Group, as in Table II
herein, nine patients totaling nine ulcers were in the
Petrolatum Group. Two of the patients were terminated from
the study because of worsening. Both had a Stage I Pressure
Ulcer. Five of the remaining seven ulcers were Stage I.
Two of the remaining seven ulcers were Stage II.
Of the Stage I Pressure Ulcers: two out of five Stage I
Ulcers resolved by the end of the study. One out of five
Stage I Ulcers showed no change. Two out of five Stage I
Ulcers worsened. concerning Stage II Pressure Ulcers: two
out of two Stage II Pressure Ulcers worsened by the end of
the study.
There were no complaints of itching, sensitivity or
rash from either of the ointments.
19
CA 02325337 2000-11-09
Table I: Formulation No. 2 Ointment
Patient Ulcer Stage Size (cm/diam) Erythema Tenderness
Start 6 Weeks Start 6 Weeks Start 6 Weeks
1 One 1.5 Resolved Moderate Absent Non Applicable
2 One 1.0 Resolved Moderate Absent Non Applicable
3 One 0.7 Resolved Moderate Absent Non Applicable
4 One 2.0 0.3 Moderate Absent Non Applicable
One 1.2 Terminated because of medical conditions
6 One 2.0 Resolved Moderate Absent Non Applicable
6 Two 1.1 0.7 Severe Mild Non Applicable
7 Two 3.0 1.0 Severe Mild Very 1V1ild
8 Two 4.0 1.5 Severe Mild Very Mild
9 Two 0.8 Resolved Moderate Absent Non Applicable
Two 1.3 Discontinued because of non-improvement
CA 02325337 2000-11-09
Table II: Petrolatum Control Group
Patient Ulcer Stage Size (cm/diam) Erythema Tenderness
Start 6 Weeks Start 6 Weeks Start 6 Weeks
1 One 1.2 Resolved Severe Moderate Mild
2 One 0.7 Resolved Moderate Absent N/A
3 One 0.7 0.7 Moderate Mild N/A
4 One 0.8 1.0 Mild Severe Not Tested
One to Two 0.2 0.4 Mild Mild N/A
6 One 1.5 Terminated because of worsening
7 One 1.3 Terminated because of worsening
8 Two 0.4 1.0 Mild Moderate N/A
9 Two 4.0 6.0 Moderate Severe Very Mild
5 Conclusions:
The ointment of Formulation No. 2 of the present
invention was found to be safe and effective in the
treatment of pressure ulcers. It helped resolve the ulcers
in a timely manner and did not have any side effects. It
also was shown to be more effective than its base of
petrolatum given the period of the study. This may be
secondary to its additional wound healing components. The
ointment of Formulation No. 2 was found therefore to also be
useful in combination with other products for the treatment
of pressure ulcers.
Footnote References:
(1) Chiarello, S. Skin Resurfacing: The Triple
Technique, Cos. Derm. Oct. 1996:26-29.
.20 (2) Resnik, B., and Resnik, S. TCA Cream Skin Peel and
Segmental Laser Resurfacing: Effective Combination
21
CA 02325337 2000-11-09
Treatment of Rhytids and Solar Dyschromia. Cos.
Derm. 1999, 31-34
(3) Bentley JP, Hunt TK, Weiss JB, Taylor CM, Hanson,
AN, Davies GH, Halliday BJ, Peptides from yeast cell
derivative stimulate wound healing. Arch Surg. 1990
May; 125(5):641-64.
(4) Crowe MJ, McNeill RB, Schlemm DJ, Greenbaigh OH.
Topical application of yeast extract accelerates the
wound healing of diabetic mice. J Burn Care Rehab.
1999 Mar-Apr; 2 (2):155-162
(5) Kaplan JZ. Acceleration of wound healing by live
yeast cell derivative. Arch Surg. 19984;
119(9):1005-1008.
(6) Loftsson T, Peterson DS, Le Goffic F, Olafsson JH.
.15 Unsaturated glycerol monoethers as novel skin
penetration enhancers. Pharmazie, 1997, June;
52(6):463-465
(7) Katiyar, S., Matsui, M., Ehmets, C., and Mulchter,
H. Polyphenolic antioxidant (-)- epigallocatechin-3-
gallate from green tea reduces UVB-induced
inflammatory responses and infiltration of
leukocytes in human skin. Photochem, Photobiol,
Feb; 69(2):148-53.
(8) Fuchs, J., Huflejt, M., Rothfuss, L., Wilson, D.,
Carcamo, G., and Packer, L. Impairment of Enzymatic
and Nonenzymatic Antioxidants in Skin by UVB
Irradiation, J. Invest. Dermatol. 93:769-773, 1989.
(9) Ghadially, R., Halkier-Scrensen, L., Elias, P.,
Effects of petrolatum on stratum corneum structure
and function, J. Am. Acad. Dermatol 1992;26:387-96.
(10) Physicians Desk Reference. 1995;49 Edition: See:
Ativan Injection, p2644; Hexadrol Injection, p1751;
Vasotec Injection, p1648.
(11) Federal Register. 1990;55:31778.31780.
22
CA 02325337 2000-11-09
EXAMPLE 2
In another study of the use of Formulation No. 2 of the
present invention for patients with Stage I & II pressure
ulcers, a randomized pilot study in the nursing home was
conducted by J. Shua-Haim MD, M. Sabo MD, J. Smith RNC at
the Dept. of Outpatient Geriatrics, Geropsychiatry & Long
Term Care Services, at the Jersey Shore Medical Center, NJ.
See footnote 12.
The purpose of this study was to investigate the
efficacy of Formulation No. 2 of the present invention, as
compared to the standard treatment for Stage I & II pressure
ulcers in a nursing home facility (including sub-acute
beds).
In this study, all newly admitted patients with Stage I
& II pressure ulcers, were randomized in two groups: a study
group included persons treated with Formulation No. 2 in one
study group and another control group including patients
treated with conventional nursing home pressure ulcer
protocol.
Formulation No. 2 was applied directly to the wound
twice a day for Stage I & II ulcers. No dressing was
applied. For Stage I, the control group was treated with
normal sterile saline (NSS) followed by A&D ointment twice
daily. Stage II ulcers were treated with NSS dressings
twice daily and Replicare hydrocolloid wound dressing every
72 hours. All study patients were turned every 2 hours for
pressure relief. All patients were evaluated daily during
wound care rounds in the facility.
As a result, a total of 23 patients were evaluated.
Eleven patients were treated with Formulation No, 2 and 12
patients were in the control group.
Locations of pressure ulcers included: sacrum & Upper
buttocks (7 occurrences), heel and ankle (8 occurrences),
hip & upper thigh (5 occurrences), lateral calf (2
occurrences), back (1 occurrence). Three Stage I patients
23
CA 02325337 2000-11-09
treated with Formulation No. 2 of the present invention had
complete healing. The average treatment length for cure was
days. Four Stage I patients in the control group showed
the following: three healed, one did not heal after 14
5 days. The average treatment length to cure in control group
was 10 days.
For Stage II wounds, results were collected after 14
days. Results for the eight patients treated with
Formulation No. 2 were: three healed, three improved and two
had no change. Results for the eight patients in the
control group were: four healed, one improved, one had no
change and two deteriorated. It was therefore concluded
that treatment with Formulation No. 2 of the present
invention for Stage I & II pressure ulcers showed a faster
healing rate, with no deterioration, when compared to
traditional nursing home treatment.
12) Shua-Haim, J., Sabo, M., Smith, J., and Ross, J.
Resurfix Treatment for Patients with Stage I and Stage II
Pressure Ulcers: A Randomized Pilot Study in the Nursing
Home, Dept. of Outpatient Geriatric, Geropsychiatry, and
Long Term Care Services, Jersey Shore Med. Center, N.J.,
Accepted for presentation at: The Gerontological Society of
America, 52nd Annual Scientific Meeting: New Perspectives on
Aging in the Post Genome Era, November 19-23, 1999, San
Francisco Hilton and Towers, San Francisco, CA.
EXAMPLE 3:
Another evaluation was conducted of Formulation No. 2
as a novel wound care product in the elderly by B. Cook, E.
Gavanis and P. Lemke.
This study recognized that Formulation No. 2 of the
present invention a multi component non-prescription wound
care ointment product which has been used to enhance healing
24
CA 02325337 2000-11-09
after trichloracetic acid skin peels, laser surgery and
dermabrasion. (See footnote references 13 14).
This study had the objective of establishing the
therapeutic effectiveness over a longer period of
Formulation 2 in treating wounds commonly found in skilled
nursing facilities. These include wounds of various degrees
of severity such as simple inflammation, Pre-Stage I
Pressure Ulcers, Stage I Pressure Ulcers and Stage II
Pressure Ulcers. Formulation No. 2 was evaluated not only
for the ability to reduce or heal the wound but also to
maintain status after healing. Residents exhibiting various
types of wounds were treated with Formulation No. 2 over a
five-week period. The wounds were assessed for size and/or
color on a weekly basis.
The study took place over a period of 5 weeks.
Residents exhibiting the various types of wounds considered
for treatment with Formulation No. 2 were identified and
grouped by a wound care nurse investigator in conjunction
with the nursing staff of the facility where the study was
performed.
Baseline wound status was assessed at the beginning of
the study and once a week for the next 5 weeks by a wound
care nurse investigator. This investigator also monitored
mandatory wound care procedures performed by the nursing
staff and adherence to the study protocol on a daily basis.
These included appropriate hydration, appropriate
nutrition (dietary consult when necessary), turning and
repositioning of residents, use of adaptive devices, use of
wheel chair cushions, air mattresses, rolls, pillows, rest
periods, use of pressure relieving overlays, cleansing of
wounds (where appropriate), and application of Formulation
No. 2 of the present invention.
Residents that were non-compliant were not be
considered for this study. Residents that become non-
compliant were eliminated from the study. Residents were
placed into groups according to their type of wound(s).
CA 02325337 2000-11-09
For example, Group 1 included residents exhibiting
areas of continual inflammation as evidenced by a pink
color. Some of these areas were previous sites of
excoriation or a Stage I Pressure Ulcer. These residents
had experienced excoriation or had Stage I Pressure Ulcers
in spite of preventative wound care procedures, including
topical application of some wound care product. The
protocol for treatment and evaluation for residents in this
group included:
1) cleansing the inflamed area with soap and tepid
water and patting the wound dry once daily or after
each episode of incontinence,
2) applying Formulation No. 2 once daily or after each
episode of incontinence,
3) monitoring on a daily basis other preventative
procedures that were utilized as per existing
nursing facility protocol and,
4) evaluating for color and change of inflamed areas
initially and once a week for 4 weeks.
Group II included residents with pre-existing Stage I
Pressure Ulcers. The protocol for treatment and evaluation
for residents in this group included:
1) cleansing the inflamed area with soap and tepid
water and patting dry once daily or after each
episode of incontinence,
2) application of Formulation No. 2 once daily or
after each episode of incontinence,
3) monitoring on a daily basis other preventative
procedures that were utilized as per existing
nursing facility protocol, and,
4) evaluating for color and size of wound at the
beginning of the study and once a week for 5 weeks.
Color of the wound was noted as "Red","Pink" or
"Resolved ". The size of the wound was measured in
length and width with an accuracy of 0.1
centimeters (cm). Areas of the body that were
26
CA 02325337 2000-11-09
difficult to measure were noted by identifying the
specific anatomical site.
Group III included residents with pre-existing Stage II
Pressure Ulcers. The protocol for treatment and evaluation
for residents in this group included:
1) irrigating the wound gently without force with
Saline Solution (NSS) and patting dry with sterile
gauze pad(s) three times daily,
2) application of Formulation 2 to affected area and
perimeter three times daily,
3) monitoring on a daily basis other preventative
procedures that where utilized as per existing
nursing facility protocol, and,
4) evaluating for color and size of wound at the
beginning of the study and once a week for 5 weeks.
The size of the wound was measured in length and
width and depth with an accuracy of 0.1 centimeters
(cm).
With respect to results of this study in Example 3, the
resident assessments were missed for week number 4 due to a
death in the wound care nurse investigator's family. The
protocols for cleansing of wounds and application of
Formulation No. 2 were continued during this week without
interruption.
The use of the term " resolved " in the study tables
means that the skin had returned to pre wound status.
For Group 1 as to treatment and prevention of
inflammation, eleven residents were entered into this group.
All residents entered the study with inflamed areas. Some
of these areas were sites of previous excoriation or Stage I
Ulcers. Other residents had sites of recent inflammation.
Three residents had previous Stage I Ulcers of their heels.
Two residents had previous excoriation of areas of their
buttock. Two residents had inflamed areas of their
buttocks. One resident had an inflamed perineal and anal
27
CA 02325337 2000-11-09
area. One resident had an inflamed perineal area. One
resident had inflammation of the perineal and back of the
neck areas. One resident had an inflamed groin area.
All residents' wounds had resolved by the end of the
second week of treatment with Formulation No. 2 of the
present invention and this continued for the next three
weeks.
(See Table III Group I Treatment and Prevention of
Inflammation Results.)
For Group II as to treatment and prevention of Stage I
Pressure Ulcers, fourteen of the sixteen residents that
entered this group finished the study. All had Stage I
Pressure Ulcers. Two of the sixteen residents did not
finish the study. One resident expired. The other one
developed severe edema secondary to venous stasis and the
attending physician changed therapies. Thirteen of the
fourteen residents that finished the study had one existing
Stage I Ulcer. One of the fourteen residents had six
existing Stage I Ulcers. This particular resident became
non-compliant by refusing therapy throughout the first week,
however, was not eliminated from the study due to insistence
by the attending physician. This resident was compliant for
the remainder of the study. The results for this resident's
ulcers were analyzed separately. This patient had six Stage
I Pressure Ulcers and refused therapy during week one.
Therapy started at week two on five of the six ulcers and
continued uninterrupted for the rest of the study. One of
the six ulcers under went biopsy during week two and was not
treated this week as per physician request. This particular
ulcer received uninterrupted treatment for the rest of the
study and will be analyzed separately.
In Example 3, there were a total of thirteen Stage I
Ulcers treated with Formulation No. 2. There was some
degree of improvement in all ulcers treated. Two of the
thirteen ulcers were resolved after one week of therapy.
Six of the thirteen ulcers were resolved after two weeks of
28
CA 02325337 2000-11-09
therapy. Seven of the thirteen ulcers were resolved after
three weeks of therapy and eleven of the thirteen ulcers
were resolved after five weeks of therapy.
The two ulcers that had not completely resolved by week
five had shown marked improvement. One of these ulcers went
from a red color and 72.0 cm2 size to a pink color and a 31
cm2 at the end of five weeks. The other went from a bright
red color to a pink color after four weeks where it remained
for week f ive .
One of the five ulcers was resolved after one week of
therapy (noted under week 2 in Table IV). Five of the five
ulcers were resolved after week two of therapy (noted under
week 3 in Table IV).
One ulcer showed improvement after one week of therapy
(noted under week 3 in Table IV). The size decreased from
16.0 cm2 to 12.2 cm2. The ulcer showed further reduction
three weeks of therapy (noted under week five in Table IV).
The size of the ulcer decreased from 16.0 cm2 at baseline to
7.5 cm2. (See Table IV: Group II Treatment and Prevention
of Stage I Pressure Ulcers Results.)
Group III: As to treatment and prevention of Stage II
Pressure Ulcers, six of the nine residents that entered this
group finished the study. All residents entered with one
Stage II Pressure Ulcer. Three of the nine residents were
eliminated from the study. Two of the residents were non-
compliant because of refusing to accept therapy and one
resident was transferred to a hospital. Five of the six
residents received uninterrupted treatment for the remaining
period of the study. One of the residents was in the
hospital for study week 2 and was analyzed separately.
Results at the end of week 1 of therapy: Two of the
five ulcers remained the same size. Three of the five
ulcers decreased in size.
Results at the end of week 2 of therapy: One out of
five remained the same size. Four (4) out of five ulcers
decreased in size.
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Results at the end of week 3 of therapy: Three out of
five ulcers decreased in size. Two out of five ulcers were
resolved.
Results at the end of week 5 of therapy: One out of
five ulcers remained the same size. Four (4) out of five
were resolved.
The Results of the hospitalized patient are as follows: The
ulcer was decreased at the end of week 1. The results were
not available for week 2. The ulcer was treated but
remained the same size for week 3. The ulcer was decreased
in size for week 5. (See Table V: Group III Treatment and
Prevention of Stage II Pressure Ulcers Results.)
CA 02325337 2000-11-09
Table III
a
Group I Results: Treatment and Prevention of Inflammation
Patient Description Baseline Week 1 Week 2 Week 3 Week 5
Number Assessment
1 Groin Pink Pink Resolved Resolved Resolved
2 Recurrent Pink Pink Resolved Resolved Resolved
Stage I of heels
3 Recurrent Pink Pink Resolved Resolved Resolved
Stage I of heels
4 Recurrent Pink Pink Resolved Resolved Resolved
Stage I of heels
Recurrent Pink Pink Resolved Resolved Resolved
Excoriation to
Buttocks
6 Recurrent Pink Pink Resolved Resolved Resolved
Excoriation to
Buttocks
7 Perineal and Pink Pink Resolved Resolved Resolved
Anal areas
8 Perineal area Pink Pink Resolved Resolved Resolved
9 Back of neck Pink Pink Resolved Resolved Resolved
and perineal
areas
Buttocks Pink Pink Resolved Resolved Resolved
11 Buttocks Pink Pink Resolved Resolved Resolved
5
31
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Table IV
Group II: Treatment and Prevention of Stage I Pressure Ulcers
Patient Anatomical Baseline Color or Therapy Therapy Therapy Therapy
Number Site of the Size (cm 0.0) of Week 1 Week 2 Week 3 Week 5
Ulcer Ulcer Length (L)
and Width
1 Bilateral Red Pink Resolved Resolved Resolved
Heels
2 8.0L x 9.0W 8.OL x 9.0W 7.OL x 8.0W 7.OL x 7.0W 6.2L x 5.0W
3 Bilateral Red Red Resolved Pink Resolved
Groin
4 Bilateral Red Red Resolved Resolved Resolved
Inner Thighs
Right Heel 1.5L x 1.5W 1.5L x 1.5W 1.OL x 1.0W Resolved Resolved
6 Bilateral 10.OL x 7.0W Resolved Resolved Resolved Resolved
Buttocks
7 Upper 5.OL x 5.0W Refused 4.2L x 4.4W Resolved Resolved
Posterior Therapy
Knees 5.O1L x 5.OW
7 Right Lower 4.OL x 4.0W Refused Biopsy 3.4L x 3.6W 3.OL x 2.5W
Leg Therapy Taken
4.01L x 4.0W
7 Left Lower 3.OL x 4.0W Refused Resolved Resolved Resolved
Posterior Therapy
3.OL x 4.0W
7 Left Calf 2.OL x 2.0W Refused 2.OL x 2.0W Resolved Resolved
Therapy
2.OL x 2.0W
7 Left Upper 5.OL x 4.0W Refused 4.OL x 2.0W Resolved Resolved
Thigh Therapy
5.OL x 4.0W
7 Left Outer 3.OL x 4.0W Refused 2.OL x 2.0W Resolved Resolved
Knee Therapy
3.OL x 4.0W
8 Perineal Red Pink Pink Resolved Resolved
Area
9 Under Red Resolved Resolved Resolved Resolved
Breasts
6.OL x 5.0W 6.OL x 5.0W 4.OL x 5.0W 4.OL x 4.0W Resolved
Penis, Bright Red Red Pink Pink Pink
11 Scrotum and
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.
Both inner
Thighs
12 11.OL x 8.OW 10.0L x 8.0W 11.OL x 3.8L x 5.OW Resolved
5.0W
13 Groin and Red Red Pink Resolved Resolved
Fold
14 Left Hi 2.OL x 8.0W 11.OL x 6.0W Resolved Resolved Resolved
Table V
Group III: Treatment and Prevention of Stage II Pressure Ulcers
Patient Anatomical Baseline Color or Therapy Therapy Therapy Therapy
Number Site of the Size (cm 0.0) of Week 1 Week 2 Week 3 Week 5
Ulcer Ulcer Length (L)
and Width (W)
and Depth
1 Sacral 1.OL x 1.5W x 0.8L x 1.5W Hospitalized 0.8L x 1.0W 0.2L x 0.5W
O.1D x 0.1D x 1.OD x 0.1D
2 Left 1.OL x 1.OW x 1.OL x 1.OW 0.5L x 0.4W 0.3L x 0.1 W Resolved
Buttock 0.1D x 0.1D x 0.1D x 0.1D
3 Right 1.5L x 1.7W x 1.5L x 1.7W 1.4L x 1.5W 1.3L x 1.4W Resolved
Buttock 0.1D x O.1D x O.1D x 0.1D
4 Sacral 2.OL x 2.0W x 2.OL x 2.5W 1.5L x 1.7W Resolved Resolved
0.4D x 0.2D x 0.1D
5 LeftHip 6.5Lx5.5Wx 4.5Lx2.3W 4.OLx2.3W 3.7Lx2.OW 3.OLx2.OW
(Old incision 0.1D x 0.1D x 0.1D x 0.1D x 0.1D
Site)
6 Left H'ip 0.3L x 0.3W x 0.3L x 0.1W 0.1L x 0.1W Resolved Resolved
0.5D x O.1D x O.1D
As a result of the Example 3 study noted in Tables III,
IV and V. Formulation No. 2 of the present invention was
shown to be therapeutically effective for prevention and
treatment of inflammation, Stage I Pressure Ulcers, and as
to Stage II Pressure Ulcers, Formulation No. 2 either
resolved (returned the skin to pre wound status), prevented
further development, or markedly improved the wounds treated
during this five week study.
33
CA 02325337 2000-11-09
A
The study noted that treatment and prevention of wounds
requires not only the application of an appropriate
medication, such as Formulation No. 2, but just as
importantly, assurance that all other underlying potentially
confounding situations such as diet, hydration,
repositioning, use of appliances, and etc. are controlled.
It was found in this study that Formulation No. 2 was
not only therapeutically effective but was also very easy to
apply and remove. This is especially important in elderly
patients whose skin integrity may be greatly reduced and
application and removal of topical medications may sometimes
cause skin tears.
References:
13) Chiarello, S. Skin Resurfacing: The Triple
Technique, Cos. Derm. Oct 1996:26-29
14) Resnik, B., and Resnik, S. TCA Cream Skin Peel and
Segmental Laser Resurfacing: Effective Combination
Treatment of Rhytids and Solar Dyschromia. Cos. Derm. 1999,
31-34
Other changes to the present invention may be made
without departing from the spirit or scope thereof, when
read in conjunction with the appended claims.
34
