Note: Descriptions are shown in the official language in which they were submitted.
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TITLE: COMPOSITIONS FOR TREATMENT OF BURNS
FIELD OF THE INVENTION
The present invention is directed to compositions for
treatment of burns in which the active agent is a
therapeutic amount of a weak acidic solution, preferably a
solution of a weak organic acid.
BACKGROUND OF THE INVENTION
Since learning the use of fire, burn injuries and
their treatment have been central concerns for human
endeavors. Burns due to skin contact with flame, hot
surfaces, hot liquids etc. are among the three most common
accidents, both at the workplace and at home. In North
America, about 95% of all burn injuries are treated by home
remedies, 2.5 million subjects seek medical advice for
burns annually in the US., about 100,000 of these require
hospitalization [Peate, WF, 1992]. These figures do not
include sunburn injury.
European figures are similar, with about 5% of burn
injuries that come to medical attention admitted to
hospital and a mortality rate of 0.2% [Jonsson, CE, 1980;
Hytonen, M et al., 1987; de Roche, R et al., 1994]. Most of
the burn injuries occur at home, most are scalding
accidents with gender and age distributions varying widely
by region, urbanization and education. The institution of
dedicated burn units is considered the most important step
of progress in burn medicine over the past decades.
The psycho-social impact of burn injuries is dramatic.
Over 95% of costs are incurred by severe injuries, mostly
(- two thirds) in terms of lost working days and to a
lesser extent for direct care [de Roche, R et al., 1994;
Khoo, AK et al., 1994; Hansbrough, JF et al., 1995].
However, there are essentially no published data that
analyze the epidemiology and impact of burn injuries which
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do not reach medical attention, but which often do cause
loss of working days and considerable, if transient
reductions in quality of life [Miller, SF, 1977; Mertens,
DM et al., 1997]. One of the most commonly occurring such
burn injuries are sunburn caused by overexposure to the
ultra violet rays of the sun. While most sunburn injuries
do not require medical attention, they can cause
considerable transient reductions in quality of life and
may also result in loss of working days.
The main immediate burn injury problems include pain
and primary infection. Scarring and functional impairment
characterize the intermediate term. Malignancy represent a
long term risk, although this is rare for most burns except
those from ultraviolet and other radiation.
Beyond the well known misery of burn pains, the
objective threats, severity and prognosis of burn injuries
are all functions of injury extent, i.e. surface area and
depth of tissue destruction. The total tissue destruction
is the sum of cells directly destroyed by heat and the much
larger number of cells dying due to local tissue responses
including edema, leukocytic infiltration, local mediators,
apoptosis and infection. These elements are fundamental
and similar to small as well as massive burn injuries, the
latter adding systemic responses in a critical care
scenario with mortality rates increasing as a quantitative
function of tissue loss, infection and post-burn
immunosuppression.
The principles of burn therapy have changed little
over the past decades, and there is some lack of basic
science and animal models for in depth analysis of the
cellular and molecular events following tissue burn injury.
There is long-standing consensus for rapid and aggressive
intervention following burn injury, including the early use
of skin grafting.
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One conclusion from this recognized need for rapid
intervention is that following the direct tissue
destruction by the hyperthermal insult, it is local and
systemic biological responses that determine much of the
post-injury course. This scenario is analogous to, and may
include, the development of shock syndromes which can be by
themselves life threatening, independently of the nature
and extent of a given injury[Cason, JS, 1981]. However,
other than shock, the immediate interference with tissue
injury responses following thermotrauma has received little
attention beyond general pain relief and precaution against
infection [Baxter, CR and Waeckerle, JF, 1988; Brofeldt, BT
et al., 1989].
Secondary cell death due to tissue burn injury
responses involves the elements of acute phase reactants
such as leukocyte extravasation and mediator release.
Vasoconstriction peripheral to the injury locus but
hyperemia and fluid loss within the injured area conspire
to reduce oxygenation, accumulate detritus, and activate
complement and apoptosis pathways for pronounced secondary
cell death. These events create the viscious circle
characteristic of even small burn injuries and their misery
[Shaw, A et al., 1994; Arturson, G, 1996]. In addition,
the injured tissue represents an ideal, immunologically
underprivileged target site for infectious agents which can
dramatically threaten the recovery process.
While the need to cover burn injuries has long been
recognized, ideal solutions are still elusive, and the
variety of proposed remedies is profuse, ranging from
honey, tree bark and animal urine or dung to potato peels
to amniotic membranes, allografts and modern plastics to
name but a few.
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The use of tannic acids (TA) (or tannic herb eschars)
as a burn remedy had been proposed early this century
[Davidson, EC, 1925] based upon ancient Chinese texts. TA
is the collective name for a group of illdefined substances
which convert putrefiable hide or skin into imputrescible
leather. The acidity of these extracts is uncertain, as
hydroxy groups from the principal trihydroxybenzene
structure are extremely weak proton donors. TA treatment
has been linked to liver necrosis in burn patients, even
death: in one report 14 of 16 TA-treated patients who died
from their burn trauma showed definitive evidence of
serious liver necrosis (reviewed in [Hupkens, P et al.,
1995]).
SUMMARY OF THE INVENTION
The present invention is directed to a composition for
treating burns. The composition comprises a
therapeutically effective amount of a weak organic acid
compatible with human skin in a suitable carrier.
In an aspect of the invention, the weak organic acid
is acetic acid or citric acid.
In another aspect of the invention, the pH of the
composition is between 2,5 and 4.5.
In yet another aspect of the invention, the suitable
carrier is an aqueous based carrier, preferably a gel form,
utilizing CarbopolTM as a gelling agent.
In yet another aspect of the invention, the
composition also includes one or more other agents selected
from sun blocking agents, skin moisturizing agents and herb
extracts.
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In yet another aspect of the invention, there is provided
a method for treating skin thermal trauma. The method comprises
applying to the affected area of the skin a therapeutically
effective amount of a weak organic acid in a suitable carrier.
In yet another aspect of the invention, the skin thermal
trauma is a sunburn.
The invention in one broad aspect comprehends the use of a
composition in an admistratable form for treating burns and
preventing delayed hyperalgesia of an affected area of skin,
wherein the composition comprises a weak organic acid selected
from the group consisting of acetic acid, vinegar, citric acid
and combinations thereof, in a pharmacologically' effective
carrier, wherein the pH of the composition ranges from
approximately 2.5 to 4.5.
Another aspect of the invention pertains to the use of a
composition in an adinistratable form for mediating the
perception of pain in an area of tissue damaged by excessive
exposure to skin thermal trauma, the administratable form being
such as to permit prolonged localized concentration of H+ ions
the source of the H+ ions being a composition containing a
therapeutically effective amount of a weak organic acid selected
from the group consisting of acetic acid, vinegar, citric acid
and combinations thereof, dispersed within a pharmacologically
effective carrier, wherein the pH of the composition is within
the range of approximately 2.5 to 4.5, and wherein said
therapeutically effective amount provides prevention of delayed
hyperalgesia.
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DETAILED DESCRIPTION OF THE PREFERRED EMBODIMEN'I'S OF Z'IIE
INVENTION
The present invention is directed to a composition for
treating burns where the composition is effective to
provide immediate interference with tissue injury responses
following thermotrauma. In contrast to topical local
analgesics, which do not affect aspects of wound healing,
local or systemic responses [Pedersen, JL et al., 1996],
the compositions of the present invention provide bot-h,
analgesia and distinct effects on the tissue in.jury
response which is reflected in the beneficial course of
scar-less healing.
The present invention relies on the observed
effectiveness of weak organic acids compatible with human
skin as a burn therapeutic agent. The effectiveness of
compositions of the invention has been shown using, for
example, food-grade vinegar, diluted acetic acid or citric
acid. Since the common element among these ingredients is
the hydrogen ion (H+), it is thereby thought to be the
active component. Local delivery of appropriately dosed H-+-
has a range of unexpected and largely unexplained
properties beneficial for the treatment of partial skin
thickness thermal injuries due to flame, hot surface
contact, scalding, as well as skin surface damage due to
overexposure to sunlight. The compositions of the invention
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have superior effectiveness when compared to any other
known burn treatment and/or remedy.
The application of a source of H+ in surface burns is
counter-intuitive, as H+ ions can cause burns themselves
when encountered in sufficient concentration.
Sources of concentrated H+ (e.g. acids) can cause
topical burns and should, thus, be avoided. In contrast,
the present invention has established that in small
concentrations, H+ ions, delivered by sources such as, for
example, acetic and citric acid, are effective for burns
therapy. These concentration/dilutions are similar to the
acetic acid content of food-grade vinegar and the citric
acid content of natural lemon juice, respectively.
Vinegar is as old the human use of alcohol, and by
around 1000 AD, hand washing with vinegar was recommended
for - what now would be labeled as - antimicrobial hygiene
in ancient medical texts from China and Arabic sources such
as Shen Tua (1031-1095 AD) [Chan, EL et al., 1994]. Vinegar
is an impure organic acid and a rich source of many
volatile contaminants [De, VM et al., 1987]. It has
possible antibacterial and antiviral effects, although the
mechanisms of this vinegar activity is unknown. Vinegar is
approved for human non-dietary use and performs well as the
main ingredient of vaginal douches although mechanisms are,
again, uncertain [Brinton, LA et al., 1990; Nyirjesy, P et
al., 1997]. None of the vinegar uses implies the new
properties disclosed here as obvious, despite the fact that
many of the now en vogue alternative health care compendia
tend to produce all-encompassing broad and scientifically
unproven claims for exceedingly lengthy lists of compounds
and substances.
The effectiveness of pure acetic acid, sodium acetate
and vinegar have rarely been compared [Brighenti, F et al.,
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19951, and never with respect to antimicrobial activity.
Although sodium acetate is used in some vaginal douches,
their effectiveness has not been measured [Chvapil, M et
al., 1978]. While acid sensitivity of bacteria is one
element of antimicrobial activity, this is insufficient to
explain the antimicrobial effects of vinegar, since some
common food-borne bacteria are highly sensitive to vinegar,
yet they survive gastric acid exposure and cause common
intestinal disease [Nishikawa, Y et al., 1993]. There is a
considerable amount of published literature on the
antimicrobial effects of vinegar [Emili, H et al., 1974;
Larghi, OP et al., 1975; Fasanella, RM, 1991; Karapinar, M
and Gonul, SA, 1992; Nishikawa, Y et al., 1993; Rund, CR,
1996], observations that are finding their way into the
food processing industries [Dickens, JA et al., 1994;
Entani, E et al., 1997].
While vinegar treatment of killed chicken prior to
freezing was shown to significantly reduce bacterial
contamination, there are no published reports on the
effects of vinegar on living skin [Dickens, JA et al.,
1994]. A widely employed skin application of vinegar occurs
in the Pacific Rim Countries where, acting as a nematocyst
inhibitor, vinegar is the recommended first aid treatment
against potentially life threatening jelly fish stings
[Fenner, PJ et al., 1985; Beadnell, CE et al., 1992;
Fenner, PJ et al., 1993].
In vitro tissue culture studies suggested that acetic
acid is toxic to human fibroblasts and keratinocytes in
concentrations of above 0.025% (reviewed in [Rund, CR,
1996]). This stands in obvious contrast to the effects of
the invention consistently observed. These data are also in
disagreement with the frequent use of vinegar douches
tolerated well and over prolonged periods of intravaginal
use [Nyirjesy, P et al., 1997]. The applicability of such
tissue culture studies to in vivo tissue is uncertain.
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Although exact molecular mechanisms remain to be
elucidated, the invention is thought to target the initial
oscillations of the viscious circle leading to secondary
cell death, thereby preventing secondary cell death with
consequent improvement of the post-injury healing process.
Forty two of 43 partial skin thickness burns have been
successfully treated with the composition.
While the effectiveness of the compositions of the
invention has been demonstrated for reasonably small (<5%
body surface), partial skin-thickness burns and sunburns
(<40% body surface) which represent the vast majority of
thermal injuries, the compositions of the invention are
also expected to have utility in wider applications such as
more severe, larger area burns and scalds. Five small (<10
cm2), full thickness skin burns have successfully been
treated with the composition. The molecular and cellular
mechanisms of the invention's effectiveness require study,
but their positive impact on localized burns is dramatic,
reproducible, fast and lasting beyond the 1-2 hrs of
initial application.
As discussed above, it is likely that the effects of
the compositions of the present invention derive from a
direct action on injurious tissue responses, an action that
stops the collateral damage due to the cascade of local
responses to thermal insult. Without the pain and
consequent vasoconstriction, without extravasation and
consequent edema, infiltration, mediator release and
blister formation, healing can and does start unimpeded. It
is possible that the controversial antimicrobial effects of
vinegar contributes to the remedial effects afforded by
sub-neutral pH gels by reducing the local load of
infectious agents and thus the risk for primary
colonization [Emili, H et al., 1974; Larghi, OP et al.,
1975; Fasanella, RM, 1991; Karapinar, M and Gonul, SA,
1992; Nishikawa, Y et al., 1993; Rund, CR, 1996; Entani, E
et al., 1997]. However, infection is not a major problem in
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the typical household burn addressed as initial and tested
target of this invention.
Formulations according to the present invention have
demonstrated efficacy treating a variety of accidental and
planned partial skin thickness first and second degree, as
well as a number of small area third degree burns. In
addition, the compositions of the invention have shown
effectiveness in the treatment of sunburns in adult
volunteers. In these experiments, test subjects were
blinded and treated consecutively with different gel
formulations that did or did not contain the active
ingredient and were otherwise indistinguishable. These
experiments firmly established the effectiveness of
compositions of the invention.
Specifically, the effects of the compositions of the
present invention include:
rapid local analgesia without the numbing of local
anesthetics,
prevention/rapid reduction of hyperemia,
prevention or reduction of local edema,
prevention of blister formation,
acceleration of wound healing,
prevention of depigmentation
prevention of delayed hyperalgesia
absence of wound infection,
absence of scarring and keloid formation.
These effects are newly discovered and disclosed here.
However, a possible antibacterial effect of vinegar and
other apolar weak acids is controversial in the literature
and, if present, could conceivably contribute to the
excellent wound healing characteristics observed following
early, transient application of the invention on surface
burn injuries.
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The compositions of the invention contain a carefully
controlled H+ concentration, typically derived from a weak
organic acid compatible with human skin, preferably, an
organic acid selected from acetic acid, food-grade vinegar
or food-grade citric acid. The composition has a pii in the
range of about 2.5 to about 4.5. The selection of the pl-H
for the composition is dependent upon the formulatiori used
and the ability of the other components in the formulatioi)
to tolerate the acidic pH. Preferably, the pH range foi
optimum effectiveness is generally about 2.5 to about 4.0,
however for the gel formulations based upon Carbopoll, a pH of
about 4.2 is preferred as it improves gelling. Carbopoll is a
trademark for a cross linked acrylic acid based polymer gelling
agent. In a preferred embodiment, the composition comprises
acetic acid or vinegar in an amount to yield up to about 0.5 to
5% acetic acid, and 2 to 8% citric acid. In a most preferred
embodiment, the composition comprises acetic acid or vinegar in
an amount equal to up to about 1% acetic acid and 5% citric acid.
The composition is provided in a form suitable for the
immediate application to the burn area. The compositiori
may be in the form of a liquid, gel, lotion, aerosol, or
may be provided in the form of a dressing for applicatiori
to the skin.
When provided as a liquid, the composition may be
simply the suitable concentration of the weak organic acid
in water with the pH of the solution adjusted to the
desired range if necessary. If desired, other water
soluble agents such as herb extracts useful for soothing
and cosmetic effects may be added provided they do not
deleteriously affect the therapeutic properties of the
composition.
The composition may also be formulated as a gel or
lotion to provide for longer lasting coverage of the
affected areas of the skin. The gel or lotion may be a
water based gel using a suitable gelling or thickening
agent. Alternatively the lotion may be provided'as an
emulsion, either an oil in water emulsion or a water in oil
emulsion. Such emulsions typically are prepared using
conveMtional ingreclients including stiffeners, emollients,
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emulsifying agents and humectants. Stiffeners are usually
oil-soluble fatty alcohols such as stearyl alcohol, cetyl
alcohol, lauryl alcohol and myristyl alcohol. Emollients
are usually isopropyl myristate, lanolin, lanolin
derivatives, isopropyl palmitate, isopropyl stearate and
the corresponding sebacates. Emulsifying agents are
preferably non-ionic and are usually sorbitan monooleate
and polyoxyl 40 stearate. Humectants are usually propylene
glycol, sorbitol, glycerin and mixtures thereof. The
ingredients for the emulsion are selected to be compatible
at the desired pH range of about 2.5 to about 4.5. Typica].
formulations are characterized according to the followinq
where percentages are by weight:
Component % by weight
Petrolatum 0-25
Stiffener 7-45
Emollient 0-15
Emulsifying agent 4-16
Humectant 7-40
Weak Organic acid 5
Water q. s . 100 õ_
The composition of the present invention is preferably
formulated as a water soluble gel which provides sustained,
local H+ concentrations. The gel formulation, for example,
can utilize Carbopoli" as the gelling agent. CarbopolT"' is a
common gelling agent in foods, cosmetics, prescription and
OTC drugs, is highly hydrophilic and rapidly removed under
running water. This allows for ease of re-application to
prolong the analgesic effects of the composition. While
CarbopolT" is one example of a gelling agent, it will be
apparent to those skilled in the art that other known
gelling agents may be utilized in addition to or in place
of CarbopolTw, provided they are effective to form a gel in
the desired pH range and do not affect the usefulness of
the organic acid.
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The composition may also include herb extracts deemed
attractive for their purported soothing and cosmetic
effects. For example, a calibrated extract of Marigold and
Aloe vera may improve odor and provide added soothing
properties. Herb extractions can be performed as short term
(20 min, 250C) vinegar or 5% acetic acid infusions of
dried, powdered herbs at pH 2.7 0.3.
The compositions of the present invention may also be
provided as an aerosol, preferably in a pump container to
provide a suitable mist spray for application to the
affected area. Such aerosol may be simply an aqueous
solution of the weak organic acid or may include other
ingredients typically provided in aerosols such as
stiffeners, humectants, or herb extracts such as aloe vera
so long as the additional ingredients do not affect the
usefulness of the composition for burn therapy. An
advantage of the aerosol form is that it can be applied to
the affected area of the skin without requiring direct
physical contact with the skin.
The compositions of the present invention may also be
provided in the form of a dressing for application to the
skin. The dressing can be gauze, or other suitable
material which is saturated with the composition of the
present invention. The use of the dressing provides a
physical barrier aiding in protection of the affected area
from potentially abrading contact and exposure to microbial
infection. This may aid in the healing of the affected
area, especially for more severe burns.
The compositions of the present invention are of
particular utility for small household and kitchen burns as
well as sunburns, i.e. over 95% of burn/scald accidents in
North America.
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Delivery of the composition of the present invention
as quickly as possible after the injury is an important
element for its full effectiveness. Delayed application of
the formulation shows slowly lessening effectiveness, but
repeated administration hours after the insult has been
tested successfully after sunburns to reduce pain,
hyperemia and blister formation, and produce relief from
thermal hypersensitivity.
Depending on wound depth and area, single or repeated
acute application of the compositions of the invention
leads to a high degree of functional recovery within
minutes and an excellent wound healing course without
blistering and scarring even in subjects that tend to
develop keloid. In subjects tested on one or more occasions
to date, the composition of the invention has not, so far,
allowed development of depigmentation and delayed
hyperalgesia.
While for most small burns, a single application of
the composition of the invention provide effective relief,
for optimum healing it is preferred that the composition be
applied 2-4 times over the first two hours after the burn
trauma.
The present invention has demonstrated, for the first
time, that topical application of H+ (hydrogen ion) through
an acidic formulation eliminates or, at least,
significantly reduces the normal symptoms (hyperesthesia,
blistering, etc.) and subsequent complications (infection,
scarring, etc.) of first, second and small area third
degree thermal injuries. H+ application also accelerates
the healing process.
The effectiveness of compositions of the invention has
been shown using food-grade vinegar, diluted acetic acid
and citric acid. Since the common element among these
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14
ingredients is the hydrogen ion (H+), iL is thereby Llioixght.
to be the active component.
In order to prolong the beneficial. effect of 11-+ with:iri
the burned area of local thermal injury, the composit.ion is
preferabl~ provided as a gel formulation, for example usii-iy
Carbopol'940 NF, a commercially available, commonly used
thickening agent in food, cosmetic and various health car-e
products. In addition, since herbs and/or their extracts
have been traditionally used for their soothing effects,
Aloe Vera, Marigold, their extracts and similar substarice.,;
may be utilized in the acid gel. However, the possible
effects or effectiveness of the latter is independent of
and cannot affect the H+ activities.
The properties and therapeutic effectiveness of H-i-
application in skin thermal trauma especially for sunburn
was empirically established. To date, the exact niolecular
mechanisms of low concentration H+ action is not known.
Preferred embodiments of the invention will now be
described in the following examples. It is to be
appreciated that the invention is not limited to t'Fie
specific examples which are merely illustrative of the
preferred embodiments.
PREPARATION OF ACID GFT.
Acetic acid and citric acid was each made to 5% (wt/v)
in H20 from glacial acetic acid (99.8 %) and solid citric
acid monohydrate, respectively. Powdered dry marigold and
Aloe Vera were then added to these acid solutions or to
commercial, food-grade vinegar to 0.15 % and 0.075 %,
respectively. This step is optional and omission of the
herbs does not affect the potency of the final products.
The mixtures were stirred at room temperature for 20 min,
and cellulose filtered, follqwed by the addition of EDTA to
0.1 %. Subsequently, solid Carbopolm 940 NF was applied
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slowly to 1.8 % while being stirred at high magnetic
setting until the suspension lost granularity. 10N NaOH was
then slowly stirred in to adjust pH of the mixtures to 4.2
for their gelling. For every 100 mL of the vinegar and
acetic acid gels, 2.8 mL of the alkaline was required,
whereas for the citric acid gel, 4.3 mL was required.
Finally, excess air was removed from the gel suspensions by
low speed (2000 rpm) centrifugation at room temperature for
5 min.
As a control to the acid gels, a neutral (pH 7.0) gel
was similarly made from H20-(herb)-EDTA and CarbopolTM 940
NF.
IN VIVO TESTING OF THE ACID GEL IN SUBJECTS WITH THERMAL
SKIN INJURY
Forty three adult volunteers were recruited into these
studies. These subjects had undergone accidental or
voluntary partial skin thickness surface burns. They were
treated with the compositions prepared as above at pH 4.2,
or aqueous solutions of 5% acetic acid at pH 2.7. Some of
the test subjects underwent testing on repeated occasions.
This included two out of five near-full thickness (third
degree) small area burns: both were successfully treated.
The main measured response elements were:
speed and extent of local analgesia,
development and extent of hyperemia,
development and extent of local edema,
development and extent of blister formation,
development and extent of wound infection,
time course of wound healing,
development and extent of depigmentation
development and extent of delayed hyperalgesia
development and extent of scarring and keloid
formation.
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The initial formulations were vinegar-based, but
subsequently formulations based on typically 5% acetic or
citric acid were developed and compared to neutral pH
(water-based) control gels. All formulations with an H+
source performed in a similar fashion, employing a blinded
subsequence (N-of-one) protocol.
The application of a liquid H+ source was reasonably
effective to provide pain relief. However, it is preferred
if the composition is provided in a carrier medium to
maintain the contact of the composition with the skin for
extended periods. Such carrier medium may be either a
physical object such as sponge, gauze, tissue or towel to
contain the liquid in the place of injury or may be a more
viscous composition such as a gel or lotion.
Application of the active ingredients in a clear gel
form is particularly preferred as it adds benefits
intrinsic to a controlled, tested and quality assured
product. In particular, a gel provides sustained delivery
of active ingredient(s) for a reasonable time as well as a
shield from microbial attack. A gel formulation and
packaging in UV resistant containers reduces loss of
volatiles [De, VM et al., 1987] and allows addition of
ingredients to augment its healing properties, smell,
cosmetic appeal, transportability and shelf life.
The effectiveness of the burn therapy of the present
invention is enhanced by quick application, preferably
right after the thermal insult. A period of less than 5
minutes between insult and application is optimal, 10-30
minutes is acceptable. The effectiveness is further
enhanced by 2 to 4 repeat applications over the first 1 to
2 hours, especially for relief of pain associated with the
thermal injury. Beyond that time frame, further
applications of the composition generally do not provide
enhanced therapeutic effect. In sunburns where burn trauma
is acquired over a prolonged period of time, the effect of
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the composition is less immediate, and in severe cases may
require repeated applications over the first several hours
of treatment.
The compositions of the invention are applied
liberally over the affected skin area directly and quickly.
Positive results are essentially immediate. The pain relief
is dramatic, quick and lasting after single or repeated
application within the first 2 hrs of trauma. If the
effect is not complete, the composition of the invention
can be freely re-applied. This is especially true for the
gel which rinses off instantly with water if required.
The immediate perception following application of the
composition of the invention is a cooling, soothing effect,
followed by receding wound pain. It has been typical that
burn victims will pursue whatever activity preceded the
accident within some 5-10 minutes and essentially forget
the insult. In superficial burns the typical post-burn
hyperalgesia disappears within 10-15 minutes, in deeper
injuries this process takes a day, but does not impede the
ability to have, for example, a normal shower, re-applying
if subjective or objective symptoms (edema, hyperemia)
linger, as was the case with several small, but full
thickness skin thermotraumas successfully treated with the
composition of the invention.
The absence of scarring has been observed with all
test applications (including the above third degree burns),
as has the absence of blistering. This applies as well to
superficial, intermediate and deep partial skin thickness
burns.
Scar formation is a serious difficulty in burn
management, yet the understanding of functional tissue
elements and tissue injury responses that drive scar
development are in their infancy [Swann, DA et al., 1988;
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Carr, CJ, 1992; Robson, MC et al., 1992; Garg, HG et al.,
1993; Gibbons, M et al., 1994; Garg, HG et al., 1995;
Ghahary, A et al., 1995; Harland, DL et al., 1997].
Analyses of the mechanisms that prevent scar formation
following treatment with the composition of the invention
may shed new light and delineate possible new therapeutic
strategies in this central area of burn management.
The effectiveness of the composition of the invention
in cases of sunburn, including one serious case with burn
to some 40% of body surface area has been demonstrated. In
sunburns the thermal and radiation injury accumulates
relatively slowly and evenly over the affected areas. The
composition of the invention was applied within one hour
after leaving the sun, i.e. much later in the burn response
process than after acute heat burns. The effect of the
composition of the invention was dramatic, but much slower.
The impressive hyperemia receded within an hour of freely
applying and re-applying the composition of the invention.
By the end of the day, this victim had a lukewarm shower to
remove some dry gel residue - the gel dissolves instantly
in water - and a thin layer was applied for the night.
There was no sign of sunburn next day, the skin was
comfortable to touch. The skin showed no hypersensitivity
to re-exposure to sun. However, sunblocks were used more
freely. There was development of natural tan, indicating
restoration of normal skin functionality.
To the first time user, the effects of H+-based burn
treatment in skin burn injuries is little short of
miraculous. Collaborators and volunteers commonly ridiculed
the process until experienced first hand: pain is very
personal.
Based on purely natural, controlled, food-grade
ingredients and designed for application to unbroken, if
injured skin, the present invention provides a new,
innovative and extremely practical home remedy for small
CA 02255521 1998-12-09
JJ-10 176 19
burn injuries - the most common of such cases. The present
invention provides an attractive, affordable, chemically
stable and easily transportable choice for the majority of
burn accidents.
Based upon the observations of the effectiveness of
the composition in treating small area third degree burns,
the compositions of the invention should be effective in
treating more severely burned victims.
The dramatic effectiveness of the compositions of the
invention in reducing surface trauma responses may imply
alternative applications in human and veterinary medicine.
For example, hypo-oxygenation is a shared aspect of burn
trauma and ulcerations such as those common in diabetes. If
the compositions of the invention affect hypoxic tissue
responses, such ulcerations could become a target for H+
therapy.
Radiation injury derived from radioactivity (e.g.
gamma- or x-ray sources) specifically induce apoptosis, and
if the compositions of the invention affects apoptosis
pathways, such injuries might be targeted by the invention.
Abnormal apoptosis has been suggested in Psoriasis and
several other chronic skin disorders and could thus provide
a possible target of H+ application. Conversely, abnormal
apoptosis is a hallmark of many, if not most cancers.
Further understanding of the mechanism(s) of action of the
present invention could lead to the development of specific
agonists/antagonists that modify tissue apoptosis responses
and provide an adjunct to cancer therapies.
Although various preferred embodiments of the present
invention have been described herein in detail, it will be
appreciated by those skilled in the art, that variations
may be made thereto without departing from the spirit of
the invention or the scope of the appended claims.
CA 02255521 1998-12-09
JJ-10 176 20
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