DESCRIPTION
WOUND DEBRIDEMENT COMPOSITIONS CONTAINING SEAPRQSE AND
METHODS OF WOUND TREATMENT USING SAME
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No.
61/485,503, filed May 12, 201 1. The contents of the referenced application are incorporated
into the present application by reference.
BACKGROUND OF THE INVENTION
A. Field of the Invention
[0002] The present invention generally relates to methods and compositions useful for
the debridement and treatment of wounds. More specifically, the present invention is related
to enzymatic wound debridement compositions comprising Seaprose and methods of wound
treatment using same.
B. Background of the Invention
[0003] The healing of wounds is a complex process which is often further
complicated by the presence of nonviable necrotic tissue in the wound area. The presence of
eschar and other necrotic tissue in a wound can impede the healing process causing the
wound to become a slow-healing or "chronic" wound. Wounds such as diabetic foot ulcers,
venous leg ulcers, arterial leg ulcers, decubitus ulcers, stasis ulcers, dermal ulcers, bums, and
pressure ulcers are examples of wounds which can become chronic wounds with the presence
of necrotic tissue that delays healing, and these wounds can be inhibited from healing.
[0004] Effective wound cleansing and debridement are long recognized prerequisites
for optimal wound healing. Necrotic tissue present in a wound bed is undesirable because it
may serve as a reservoir for bacterial growth, contain elevated levels of inflammatory
mediators that promote chronic inflammation at the wound site, and impair cellular migration
necessary for wound repair. It is increasingly well recognized that clearing a wound bed of
necrotic tissue is an important step that may facilitate the healing process for a variety of
wound types, particularly burn wounds and various chronic wounds.
[0005] A number of different modalities exist for wound debridement. The four most
common debridement methods are surgical, autolytic, enzymatic, and mechanical. Each of
these has its own benefits and shortcomings, depending on the wound type and the condition
of the patient.
[0006] Enzymatic debridement is the process of topically applying an enzymatic
debridement agent to the wound to digest eschar and other necrotic tissue, thereby facilitating
removal of the necrotic tissue. Enzymatic debridement agents are those enzymes that can
rapidly digest necrotic tissue without injury to living cells, thereby speeding the healing
processes. Use of such debridement agents have included the employment of a wide variety
of microbial, plant and animal materials, even things such as maggots or blowfly larvae, but
more commonly, the enzyme papain derived from the papaya tree, the enzyme trypsin
derived from animal pancreas, and the enzyme collagenase derived from the bacteria
Clostridium histolyticum. The mechanism in almost all of these cases has been identified
with enzymatic activity.
[0007] Healing of wounds is delayed by the presence of pus, tissue debris, bacteria,
exudates and eschar. The major constituents of wound eschar are proteins, such as collagen,
fibrin, elastin, fibronectin, and hemoglobin. Of these, various types of wound eschar have
been demonstrated to be predominantly composed of the fibrous proteins collagen, elastin,
and fibrin. The primary purpose of the debridement enzyme is to clean a wound of all of the
various necrotic tissue elements and to thin out thick exudative secretions. When properly
applied to selected patients, certain proteolytic enzymes cleanse infected proteinous surfaces
of their inflammatory exudate without harm to living tissues, facilitate the drainage of areas
of local purulent, sanguineous and fibrinous accumulations, promote the liberation of hidden
bacteria, thereby exposing them to antimicrobial agents and native immune forces, and
increase the rate of repair of previously infected wounds. This enzymatic action can also be
of benefit for the treatment of inflammatory skin diseases such as psoriasis and eczema.
[0008] Topical ointment and cream compositions containing proteolytic enzymes
such as papain, trypsin, and collagenase have been widely employed for enzymatic wound
debridement particularly in patient populations not amenable to surgical debridement.
Compositions containing thermolysin (US patent application 2003/0198631) and bromelain
(US patent 4,197,291) have also been disclosed for use in wound debridement.
[0009] An example of a commercially available enzymatic debridement ointment is
one containing a bacterially derived collagenase used to degrade collagen components in
wounds. Another product is one containing fibrinolysin which is specifically used to digest
fibrin debris. These products contain enzymes that are potent and specific for their
substrates. Such high debridement specificity results in less harm to viable tissue and less
irritation to patients. However, since these enzymes are substrate specific, debridement of
nonviable necrotic tissue may be slow or incomplete because of the various protein elements
present in necrotic tissue of chronic wounds. For example, collagenase is very specific to
digest collagens, but not very effective for other proteins. Likewise, fibrinolysin is
specifically used to digest fibrin debris, but not very effective for other proteins.
[0010] Because of the diversity of proteins in wound eschar and other necrotic tissue,
commercially available compositions containing nonspecific proteases, such as papain, were
used for wound debridement with good clinical efficacy. However, most of these products
are grandfathered (DESI) drugs and are no longer commercially available.
SUMMARY OF THE INVENTION
[001 1] The present invention is generally directed to wound debridement
compositions containing the proteolytic enzyme Seaprose and methods of wound treatment
for the enzymatic debridement of wounds with such compositions. Such wounds being
treated or debrided with the compositions of the present invention can include necrotic tissue
(e.g., eschar).
[0012] In one aspect of the present invention, there is disclosed a method of treating a
wound comprising topically applying to the wound a composition comprising Seaprose,
wherein the wound is in need of debridement. The wound can be present on a person's skin
(e.g., the epidermal and/or dermal layer of the skin can be damaged). The wound can include
necrotic tissue (e.g., eschar). In another aspect, the amount of Seaprose is a wound
debridement effective amount of Seaprose. In one embodiment, the composition further
comprises a pharmaceutically acceptable topical carrier. In one embodiment, the wound is a
chronic wound. In various embodiments, the chronic wound is a diabetic foot ulcer, a venous
leg ulcer, an arterial leg ulcer, a decubitus ulcer, a stasis ulcer, a dermal ulcer, a burn, or a
pressure ulcer.
[0013] In another aspect of the present invention, there is disclosed a method of
enzymatic wound debridement comprising topically applying to a wound in need of
debridement a composition comprising a debridement effective amount of Seaprose. Again,
the wound can be present on a person's skin (e.g., the epidermal and/or dermal layer of the
skin can be damaged). The wound can include necrotic tissue (e.g., eschar). In one
embodiment, the composition further comprises a pharmaceutically acceptable topical carrier.
In one embodiment, the wound is a chronic wound. In various embodiments, the chronic
wound is a diabetic foot ulcer, a venous leg ulcer, an arterial leg ulcer, a decubitus ulcer, a
stasis ulcer, a dermal ulcer, a burn, or a pressure ulcer. The wound can include necrotic
tissue (e.g., eschar).
[0014] In yet another aspect of the present invention, there is disclosed a method of
treating a wound comprising injecting into the wound a composition comprising Seaprose,
wherein the wound is in need of debridement. The wound can be present on a person's skin
(e.g., the epidermal and/or dermal layer of the skin can be damaged). The wound can include
necrotic tissue (e.g., eschar). In another aspect, the amount of Seaprose is a wound
debridement effective amount of Seaprose. In one embodiment, the composition further
comprises a pharmaceutically acceptable carrier suitable for injection. In one embodiment,
the wound is a chronic wound. In various embodiments, the chronic wound is a diabetic foot
ulcer, a venous leg ulcer, an arterial leg ulcer, a decubitus ulcer, a stasis ulcer, a dermal ulcer,
a burn, or a pressure ulcer.
[0015] In still another aspect of the present invention, there is disclosed a method of
enzymatic wound debridement comprising injecting into a wound in need of debridement a
composition comprising a debridement effective amount of Seaprose. The wound can be
present on a person's skin (e.g., the epidermal and/or dermal layer of the skin can be
damaged). The wound can include necrotic tissue (e.g., eschar). In one embodiment, the
composition further comprises a pharmaceutically acceptable carrier suitable for injection. In
one embodiment, the wound is a chronic wound. In various embodiments, the chronic wound
is a diabetic foot ulcer, a venous leg ulcer, an arterial leg ulcer, a decubitus ulcer, a stasis
ulcer, a dermal ulcer, a burn, or a pressure ulcer.
[0016] In another aspect of the present invention, there is disclosed a composition for
the debridement of wounds comprising a wound debridement effective amount of Seaprose
and a pharmaceutically acceptable carrier for topical application to the wound or for injection
into the wound. The wound can be present on a person's skin (e.g., the epidermal and/or
dermal layer of the skin can be damaged). The wound can include necrotic tissue (e.g.,
eschar).
[0017] In one embodiment, the compositions of the present invention are sterile. In
one embodiment, the Seaprose is in a dissolved state in the pharmaceutically acceptable
carrier. In another embodiment, the Seaprose is in a dispersed state in the pharmaceutically
acceptable carrier. Further, the Seaprose can be isolated or purified Seaprose. Also, the
wound debridement capabilities of the compositions of the present invention can be used in
lieu of surgical removal of necrotic tissue.
[0018] Unless otherwise specified, the percent values expressed herein are weight by
weight and are in relation to the total composition.
[0019] As used in this specification and claim(s), the words "comprising" (and any
form of comprising, such as "comprise" and "comprises"), "having" (and any form of having,
such as "have" and "has"), "including" (and any form of including, such as "includes" and
"include") or "containing" (and any form of containing, such as "contains" and "contain") are
inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
[0020] The compositions and methods for their use can "comprise," "consist
essentially of," or "consist of any of the ingredients or steps disclosed throughout the
specification. With respect to the transitional phase "consisting essentially of," in one nonlimiting
aspect, a basic and novel characteristic of the compositions and methods disclosed in
this specification includes the compositions' enhanced enzymatic debridement activity.
[0021] Other objects, features and advantages of the present invention will become
apparent from the following detailed description. It should be understood, however, that the
detailed description and the specific examples, while indicating specific embodiments of the
invention, are given by way of illustration only, since various changes and modifications
within the spirit and scope of the invention will become apparent to those skilled in the art
from this detailed description.
[0022] The term "effective," as that term is used in the specification and/or claims,
means adequate to accomplish a desired, expected, or intended result.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1. A plot of the results of an in-vitro study comparing the degradation of
pig eschar by bromelain, thermolysin, and Seaprose gels at 37°C within a 24-hour period.
[0024] FIG. 2. An image of in vivo pig wounds after 24 hour treatment with a
Seaprose hydrogel compared with a control (moist wound care).
[0025] FIG. 3. A graph of the results of the in-vivo pig study comparing the
debridement of wounds with Seaprose hydrogel compared with a control (moist wound care).
DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0026] The present invention is directed to enzymatic wound debridement
compositions comprising Seaprose and methods of wound treatment and enzymatic wound
debridement using same.
A. Compositions
[0027] The compositions of the present invention are compositions for the
debridement of wounds comprising a debridement effective amount of Seaprose and can
further comprise a pharmaceutically acceptable carrier. The compositions of the invention
may include Seaprose as the sole ingredient or also include a pharmaceutically acceptable
carrier. The compositions of the invention may further comprise pharmaceutically active
ingredients, cosmetically active ingredients, and vulnerary agents (e.g., growth factors)
suitable for topical or injectable administration to wounds.
[0028] In-vitro studies demonstrated that a composition containing Seaprose was
surprisingly more effective in digesting eschar material (FIG. 1) than were compositions of
bromelain and thermolysin.
1. Seaprose
[0029] Seaprose is a semi-alkaline protease produced by the fermentation of the
fungus Aspergillus melleus and is commercially available in a powder form from Amano
Enzyme, Inc., Japan under the trade name SEAPROSE S®. Seaprose may be prepared by
either a liquid or solid fermentation process using techniques known by one of skill in the art.
Seaprose has also been referred to as onoprose, promelase, promelasum, Jeoase,
FLAMINASE® (Prodotti Formenti S.r.l., Milan Italy), and Aspergillus melleus semi-alkaline
proteinase.
[0030] The major protease in Seaprose is a semi-alkaline protease with a molecular
weight around 3 1 kDa. It can also contain other enzymes such as amylase, which is a
hydrolytic enzyme which breaks down carbohydrates. Alternatively, Seaprose can be
purified or isolated by standard techniques known to those of skill in the art. Seaprose shows
great stability at an optimal pH range of from 5 to 9, and an optimal temperature below 50°C.
These conditions are suitable for application of the enzyme in wounds and favorable for drug
formulation and manufacture.
[0031] Seaprose has previously been used for a variety of medical indications and
treatment; however, it has never previously been used in a topical or injectable form for use
as a wound debriding agent. For example, Seaprose has been shown to possess in-vitro
mucolytic activity (Braga 1990) and to effectively treat patients with bronchitis by oral
administration of Seaprose capsules (Braga 1993), (Moretti 1993). Seaprose has shown anti¬
inflammatory activity against many different inflammatory conditions in animal models
(Fossati 1991). Seaprose was shown to be effective in treating patients with inflammatory
venous disease by oral administration of Seaprose tablets (Bracale 1996). Seaprose has been
used to treat abdominal pain due to pancreatitis (US patent 7,459,155). Seaprose has been
used to treat complications of puerperal surgical wounds by oral administration of Seaprose
30 mg tablets (Dindelli 1990).
[0032] According to the present invention, Seaprose may be in a dissolved state
and/or a dispersed state in the pharmaceutically acceptable carrier. The Seaprose may also be
encapsulated. It may also be used neat without a carrier. Seaprose can also be used in a
purified or isolated form.
[0033] The amount of Seaprose in a composition with a pharmaceutically acceptable
carrier is an amount effective for wound debridement and can generally range from about
0.001% w/w to about 10 %w/w; or from about 0.01% to about 9%; or from about 0.1% to
about 8%; or from about 0.1% to about 0.9%; or from about 0.2% to about 0.8%; or from
about 0.3% to about 0.7%; or from about 0.4% to about 0.6%; or about 0.5%; or from about
0.5% to about 7%; or about 1% to about 6%; or from about 1.5% to about 5%; or from about
0.5% to about 1.5%; or from about 0.6% to about 1.4%; or from about 0.7% to about 1.3%;
or from about 0.8% to about 1.2%; or from about 0.9% to about 1.1%; or about 1%. Such
amount will be that amount which effectively debrides necrotic tissue in wounds.
2. Pharmaceutically Acceptable Carriers
[0034] The compositions of the present invention may comprise various
pharmaceutically acceptable carriers suitable for topical delivery and compatible with
Seaprose. Non-limiting examples include lotions, creams, emulsions, ointments, gels, pastes,
solutions, aerosol sprays, aerosol foams, non-aerosol sprays, non-aerosol foams, powders,
liquid solutions, liquid suspensions, films, and sheets. The compositions may be impregnated
in gauzes, bandages, or other wound dressing materials for topical delivery.
[0035] The compositions of the invention may further comprise functional ingredients
suitable for use in topical compositions and compatible with Seaprose. Non-limiting
examples include absorbents, antimicrobial agents, antioxidants, binders, buffering agents
(including Tris buffer solutions), bulking agents, chelating agents, colorants, biocides,
deodorant agents, emulsion stabilizers, film formers, fragrance ingredients, humectants, lytic
agents, enzymatic agents, opacifying agents, oxidizing agents, pH adjusters, plasticizers,
preservatives, reducing agents, emollient skin conditioning agents, humectant skin
conditioning agents, moisturizers, surfactants, emulsifying agents, cleansing agents, foaming
agents, hydrotopes, solvents, suspending agents, viscosity control agents (rheology
modifiers), viscosity increasing agents (thickeners), and propellants. Listings and
monographs of the functional ingredients described herein are disclosed in The International
Cosmetic Ingredient Dictionary and Handbook (INCI), 12th Edition, 2008, hereby
incorporated by reference.
[0036] Suitable pharmaceutically acceptable topical carriers include an anhydrous
hydrophilic wound debrider composition as disclosed in: US patent 6,548,556 herein
incorporated by reference; a spray-on topical wound debrider composition as disclosed in US
patent 7,785,584 herein incorporated by reference; an enzymatic wound debriding
composition as disclosed in international PCT application PCT/US 10/59409 herein
incorporated by reference; a hydrogenated castor oil ointment as disclosed in US patent
6,479,060 herein incorporated by reference; an anhydrous hydrophilic absorbent wound
dressing as disclosed in US patent 6,399,092 herein incorporated by reference; and a
hydrogel wound dressing as disclosed in US patent 5,902,600 herein incorporated by
reference.
[0037] The compositions of the present invention may also comprise various
pharmaceutically acceptable carriers suitable for injectable delivery compatible with
Seaprose.
[0038] The compositions of the present invention may be packaged in any package
configuration suitable for topical or injectable products. Non-limiting examples for topical
products include bottles, lotion pumps, toddles, tubes, jars, non-aerosol pump sprayers,
aerosol containers, syringes, pouches, and packets. The packages may be configured for
single-use (one dose) or multiple-use administration. Non-limiting examples for injectable
products include vials, syringes, micro-needle syringes, or bags.
[0039] The compositions of the present invention may also be sterile. They may be
sterilized via an aseptic manufacturing process or sterilized after packaging by methods
known in the art.
3. Manufacture
[0040] The compositions of the present invention may be manufactured by suitable
processing methods known by one of skill in the art for topical and/or injectable products.
For example, Seaprose can be admixed with the pharmaceutically acceptable carrier.
Alternatively, Seaprose can be applied to a wound in a neat form (e.g., without carrier).
B. Methods of Use
[0041] The composition of the present invention may be used in methods of treatment
for the debridement of wounds in need of debridement. The method comprises applying to
the wound a composition comprising Seaprose either by topical application or by injection.
After topical application, the wound may be covered with a wound dressing such as a gauze
pad. The composition may be applied to a dressing such as a gauze pad first and then applied
to the wound surface. The application amount depends on the severity and type of the wound
and nature of the subject.
[0042] The composition can be applied to the wound periodically, for example, daily.
A therapeutic regiment could be followed to include periodic dressing changes with wound
cleansing and application of fresh composition between changes until the debridement of the
necrotic tissue is complete. Use of the composition could also be discontinued when
debridement of necrotic tissue is complete.
[0043] Bums, acute wounds, or chronic wounds may be treated according to the
methods of the present invention. Non-limiting examples of chronic wounds include diabetic
foot ulcers, venous leg ulcers, arterial leg ulcers, decubitus ulcers, stasis ulcers, dermal ulcers,
burns, and pressure ulcers.
EXAMPLES
[0044] The following examples are included to demonstrate certain non-limiting
aspects of the invention. It should be appreciated by those of skill in the art that the
techniques disclosed in the examples which follow represent techniques discovered by the
applicants to function well in the practice of the invention. However, those of skill in the art
should, in light of the present disclosure, appreciate that many changes can be made in the
specific embodiments which are disclosed and still obtain a like or similar result without
departing from the spirit and scope of the invention.
EXAMPLE 1
(Exemplary Formulations)
[0045] The following Tables provide non-limiting examples of formulations
containing Seaprose of the present invention:
Table 1—Gel*
Process: A gel was made with the HEC and Tris buffer. SEAPROSE S was admixed with the HEC gel. The
viscosity of the gel gradually reduced over time possibly due to the amylase present in the Seaprose material
degrading the HEC.
Table 2—Gel*
Process: SEAPROSE S was admixed with the CURASOL Gel Wound Dressing to form a clear gel. The
viscosity was maintained over time.
Table 3—Cream*
Process: Methylparaben, propylparaben and glycerin were dissolved in the Tris buffer solution at 70°C.
Emulsifying wax and isopropyl palmitate were added to the above solution at 70°C and mixed to form an
emulsion. The emulsion was cooled to 35°C at which time SEAPROSE S was admixed with the emulsion. A
white cream was obtained.
Table 4—Ointment
Process: An Active Phase was made by melting a mixture of half of the amount of PEG-600 and half of the
amount of poloxamer-407 at 70°C, cooling the mixture to 35°C at which time SEAPROSE S was admixed with
the mixture. A Main Phase was made by melting a mixture of white petrolatum and the remaining half of the
amount of PEG-600, and the remaining half of the amount of poloxamer-407 at 70°C, cooling the mixture to
35°C. The Active Phase was then admixed with the Main Phase. The resulting mixture was mixed at RT for 45
minutes.
EXAMPLE 2
(In vitro Digestion of Pig Burn Eschar)
[0046] The gel formula in Table 1 (1% Seaprose Gel) and each of the following two
gel formulas (1% Thermolysin Gel and 10% Bromelain Gel) were used in an in-vitro study to
compare the degradation of pig eschar by each gel formula.
Table 5—1% Thermolysin Gel
[0047] The study was conducted in-vitro using eschar materials obtained from pig
burn wounds. The eschar materials were dried completely. The dry weight was used as
baseline. Samples of the dried eschar weighing 40-60 mg were moisturized with 50 m of
Tris buffered saline. The moisturized eschar samples were immersed in 3 g of each of the
three gel formulas. The gels with eschar were stored at 37°C for 24 hours. After 24 hours,
the samples were centnfuged at 5000 rpm for 5 minutes. The supernatant was discarded and
water was added to wash the precipitates. The samples were centrifuged again. Another
wash step was performed and then the precipitates were freeze-dried. The dry weights of the
precipitates were used to calculate the degradation percentage based on the baseline dry
weights. The results are presented in FIG. .
[0048] The results in FIG. 1 demonstrate that the Seaprose gel was more effective and
exhibited superior potency in digesting the eschar material as compared to the 1%
thermolysin gel (Table 5) and 0% bromelain gel (Table 6) within the 24 hour period. The
quickness at which the Seaprose gel digested the eschar as compared to the 1% thermolysin
gel and the 10% bromelain gel was totally unexpected, because thermolysin and bromelain
are both known in the art to be a fast debriding enzymes {see, e.g., U.S. Patent Publication
2003/0198631 and U.S. Patent 8,1 19,124, respectively). The results of the in-vitro study
indicate that Seaprose can efficiently and effectively target and digest eschar proteins and
therefore, it is suitable as a superior enzymatic wound debrider which can be used for the
treatment of wounds in need of debridement.
EXAMPLE 3
(In vivo Debridement of Pig Burn)
[0049] In this in vivo pig study, eschars were formed on the backs of pigs by
introducing burn wounds using heated brass rods and allowing the formation of dry eschars
over several days. There was a visual effect of Seaprose (SAP) on many wounds in
comparison to control after one day of treatment (FIG. 2). Overall, SAP exhibited more rapid
complete debridement of the eschars when compared against a control (non-adherent premoistened
wound dressing with saline) (FIG. 3).
[0050] The particulars of this in vivo study are as follows. Pigs were anesthetized, the
torso shaved with clippers and a razor, and washed with vedadine. Then an isopropyl rinse
was performed to sterilize the surgical field. Twenty 2-cm wounds were created on the
dorsum of each pig. The wounds were created using solid brass rods, heated to 100°C in
sand baths, held on the skin for 45 seconds. The wounds were left to dry for five days, giving
the eschars time to form, with protective foam dressings being replaced every other day
during eschar formation. After eschar formation and on a daily basis for treatments, the
wounds were cleaned, photographed, treated according to the treatment randomization
scheme, and dressed with non-adherent dressings (pre-moistened with saline) secured with
Transpore tape and occlusive secondary dressings. Statistical significance for the number of
eschars fully debrided was determined using Fisher's Exact test.
[0051] Treatment regimen for this study included use of a Seaprose containing
formulation prepared in the following manner and a control which consisted of a non¬
adherent pre-moistened wound dressing with saline): (1) Seaprose S powder was prepared
(see Table 7 below) and lOOmg of said powder was directly applied to the wound; and (2) a
gel was prepared (see Table 8 below) and 400mg of said gel was applied on top of the
Seaprose S powder. Treatments were performed once a day for a fifteen day period. After
the initial 24 hours of treatment, visual differences were apparent for many Seaprose-treated
wounds, including pitting of the eschar and in some cases limited exposure of healthy wound
tissue (FIG. 2). Over the fifteen day treatment period, Seaprose treatment produced a
consistent trend of complete debridement of more wounds than the control (Seaprose
treatment achieved statistical significance (p<0.05) versus the control on day 13 of treatment)
(FIG. 3).
Table 7—Seaprose S Powder*
*Process: Seaprose S and sorbitol were mixed at room temperature (approximately 20 to 25°C) to obtain a
homogenous powder.
Table 8—Gel*
cooling, Hispagel-200 was added. Clear and transparent gel was obtained.
REFERENCES
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Braga P.C, Moretti M., Piacenza A., Montoli C.C. and Guffanti E.E., Effects of
Seaprose on the Rheology of Bronchial Mucus in Patients with Chronic Bronchitis. IntJClin
Pharmacol Res. 1993;13(3): 179-185.
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US Patent Documents
US Patent 4,197,291 Klein et al.
US Patent 5,902,600 Woller et al.
US Patent 6,172,219 Callegaro et al.
US Patent 6,399,092 Hobson et al.
US Patent 6,479,060 Jones et al.
US Patent 6,548,556 Hobson et al.
US Patent 7,459,155 Margolin et al.
US Patent 7,642,079 Cayouette et al.
US Patent 7,785,584 Jones et al.
US Patent Application 2003/0026794 Fein
US Patent Application 2003/0198631 Shi et al.
US Patent Application 2003/0198632 Shi et al.
US Patent Application 2010/0124549 Studin
US Patent Application 2010/0254968 Desser et al.
Foreign Patent Documents
WO 2008/019417
PCT/USlO/59409
JP 560922 17A (ABSTRACT)
CLAIMS
1. A method of debriding a wound that includes necrotic tissue comprising applying to
the wound a composition comprising Seaprose, wherein application of the
composition debrides necrotic tissue in the wound.
2. The method of claim 1, wherein the necrotic tissue is an eschar.
3. The method of any one of claims 1-2, wherein the composition is topically applied to
the wound.
4. The method of any one of claims 1-3, wherein the composition further comprises a
pharmaceutically acceptable topical carrier.
5. The method of any one of claims 1-4, wherein the wound is a chronic wound.
6. The method of claim 5, wherein the chronic wound is a diabetic foot ulcer, a venous
leg ulcer, an arterial leg ulcer, a decubitus ulcer, a stasis ulcer, a dermal ulcer, a burn,
or a pressure ulcer.
7. The method of any one of claims 1-6, wherein the composition includes 0.1 to 2% by
weight of Seaprose.
8. The method of claim 7, wherein the composition includes 0.5 to 1% by weight of
Seaprose.
9. The method of any one of claims 1-8, wherein the Seaprose is isolated or purified
Seaprose.
10. The method of any one of claims 1-9, wherein the composition is formulated as a gel,
cream, or ointment.
11. The method of any one of claims 1-10, wherein the composition further comprises
glycerin polyacrylate clatharate, glycerin, hydroxyethylcellulose, an emulsifying wax, or
petrolatum, or any combination thereof.
12. The method of any one of claims 1-2 and 5-9, wherein the composition is injected into
the wound.
13. The method of any one of claims 1-2, 5-9, and 12, wherein the composition further
comprises a pharmaceutically acceptable injectible carrier.
14. Use of Seaprose for the preparation of a composition for the debridement of a wound
comprising necrotic tissue.
15. The use of claim 14, wherein the necrotic tissue is an eschar.
16. The use of any one of claims 14-15, wherein the composition further comprises a
pharmaceutically acceptable topical carrier.
17. The use of any one of claims 14-16, wherein the wound is a chronic wound.
18. The use of claim 17, wherein the chronic wound is a diabetic foot ulcer, a venous leg
ulcer, an arterial leg ulcer, a decubitus ulcer, a stasis ulcer, a dermal ulcer, a burn, or a
pressure ulcer.
19. The use of any one of claims 14-18, wherein the composition includes 0.1 to 2% by
weight of Seaprose.
20. The use of claim 19, wherein the composition includes 0.5 to 1% by weight of
Seaprose.
21. The use of any one of claims 14-20, wherein the Seaprose is isolated or purified
Seaprose.
22. The use of any one of claims 14-21, wherein the composition is formulated as a gel,
cream, or ointment.
23. The use of any one of claims 14-22, wherein the composition further comprises
glycerin polyacrylate clatharate, glycerin, hydroxyethylcellulose, an emulsifying wax, or
petrolatum, or any combination thereof.
24. The use of any one of claims 14-15 and 17-21, wherein the composition further
comprises a pharmaceutically acceptable injectible carrier.
25. A topical composition for the debridement of wounds comprising a wound
debridement effective amount of Seaprose and a pharmaceutically acceptable topical
carrier.
26. The topical composition of claim 25, wherein the composition includes 0.1 to 2% by
weight of Seaprose.
27. The topical composition of claim 26, wherein the composition includes 0.5 to 1% by
weight of Seaprose.
28. The topical composition of any one of claims 25-27, wherein the Seaprose is isolated
or purified Seaprose.
29. The topical composition of any one of claims 25-28, wherein the composition is
formulated as a gel, cream, or ointment.
30. The topical composition of any one of claims 25-29, wherein the composition is an
ointment comprising petrolatum.
31. The topical composition of any one of claims 25-29, wherein the composition is a gel
comprising glycerin polyacrylate clatharate.
32. The topical composition of any one of claims 25-29, wherein the composition is a gel
comprising hydroxyethylcellulose.
33. The topical composition of any one of claims 25-29, wherein the composition is a cream
comprising glycerin and an emulsifying wax.