EP0983085A2 - Compositions and means for the treatment of burns and other cutaneous traumas - Google Patents
Compositions and means for the treatment of burns and other cutaneous traumasInfo
- Publication number
- EP0983085A2 EP0983085A2 EP98921713A EP98921713A EP0983085A2 EP 0983085 A2 EP0983085 A2 EP 0983085A2 EP 98921713 A EP98921713 A EP 98921713A EP 98921713 A EP98921713 A EP 98921713A EP 0983085 A2 EP0983085 A2 EP 0983085A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- debriding
- wound
- skin
- debrided
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/38—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F15/00—Auxiliary appliances for wound dressings; Dispensing containers for dressings or bandages
- A61F15/001—Packages or dispensers for bandages, cotton balls, drapes, dressings, gauze, gowns, sheets, sponges, swabsticks or towels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F2013/00089—Wound bandages
- A61F2013/00157—Wound bandages for burns or skin transplants
Definitions
- the present invention relates to the treatment of traumatized skin. More
- the invention relates to compositions and means for promoting
- cutaneous burn trauma onset, severity, complexity, short and long term implications the cutaneous burn trauma will be used here as an example to other cutaneous traumas.
- the traumatized skin (burned tissue) the eschar may be of different depths
- the eschar characteristics may depend on the traumatizing agent
- burn's depth is changing from point to point and the eschar' color
- debridement This removing of the dead tissue is termed "debridement".
- the concept of debridement is as old as
- bleeding tissues is the procedure of choice. In the case of burns, because of
- the severed blood vessels are the ones that will grow
- debrided tissue is typical and made of healthy dermal collagen, subdermal
- Fibrinolysin-desoxyribonuclease (Elase) compounds were or still are in
- microbacterial, vegetable or even animal origin were tested and some even
- Bacillus subtilis Sutilains (Travase), Streptococci:
- Streptokinase-streptodornase plants such as the Papaya (Papain) or
- tissue could not support an autogenous or non autogenous living graft
- burn treatment the following choices of burn treatment protocols may be
- the area that needs to be grafted is
- raw debrided tissue dictates usually an autograft with an additional
- the new treatment means are based on the discovery that both the above
- the first is an undertreatment, leaving the dead eschar
- the second is an overtreatment, debriding aggressively the
- necrotic tissue prevents secondary germ's contamination and sepsis. Its
- neo-vascularization does not proceed as readily in the interface layer as in
- the graft with their host/graft direct anasthomosis or budding potential.
- epithelial remnants in the skin adnexae are given the right conditions for
- epithelialization prevents the formation of the granulation tissue
- these areas may be grafted by
- the present invention provides, inter alia, a skin pre-heahng
- composition for the pre-treatment of traumatized skin, comprising an
- the debriding agent is present in an amount and nature
- the debriding agent comprises:
- the debriding agent is derived from pineapple. Typical debriding
- agents of this kind include, e.g., Bromelain or a derivative or fraction
- the invention is directed to an early coverage set for the
- the Keratocyte described above and promotion of its heahng, comprising a protective dressing that may be provided with Keratocyte growth promoting agent(s).
- the Keratocyte may be provided with Keratocyte growth promoting agent(s).
- growth promoting agent comprises an artificial dermis.
- agent comprises one or more growth hormones.
- the invention further provides a method for treating a patient suffering from trauma of the skin, said method comprising the steps of:
- the debridement procedure is carried out
- Keratocyte propagation in
- Figure 1 is a photography of a fresh, mixed depth, scaled burn of the
- white-gray area 2 is deeper and is of a second-deep (deep-dermal)
- Figure 2 is a photography of the same burn of Fig. 1 after an enzymatic
- Figure 3 is a photography of a deep (nominal third degree) burn of the
- the thickness dermal eschar is present.
- the whitish areas marked 7 shows clearly a very thin LL. with its typical granular pinkish aspect and
- area marked 8 is a full
- Figure 4 is a photography of a wider field and general appearance of
- Figure 5 is a photography of a deep mixed flame burn (similar in
- Figure 6 is a drawing of a soaking dressing whereas 12 represents the
- absorbent material that moisturizes the wound's surface by capillary
- Container 13 represents the germ-free soaking liquids that
- a draining tube 15 drains the access fluids from the wounds site into a collecting
- Figure 7 is a schematic drawing representing the piglet bioassay site
- numbered 19 is the deep, full thickness burn.
- excision 20 represents all the different areas (17, 18 and 19) of the
- FIG 8 is a drawing representing the biopsy (Fig 7 no. 20) where the
- Zone 21 is the
- Fig. 9 is a drawing of a unit dose debriding matrix carrier saturated with lyophihzed enzyme, with an optional rigid frame 125 made of
- inert matrrials such as plastic as in figs. 10 and 11.
- Fig. 10 iUustrates a placing device for the matrix carrier, with or
- debriding matrix carrier, 40 is released.
- Fig. 11 is a drawing of a placing device for the matrix carrier in cross
- Said device comprises a cartridge, 43, which contains one or more unit dose debriding matrix carriers, 44, may be separated one
- debriding agent's solvent may be a part of the matrix carrier itself
- a matrix carrier can be any suitable matrix carrier.
- Fig. 12 is a drawing of a unit dose, uniform, dispersal device in cross section.
- Said device comprises a cartridge, 30, which contains
- peeling blade 36, is moved from close to side 37 to close to side 38, and back to close to side 37. At the first half of each cycle, i.e. when
- the "peehng blade” 36 may be in the form of a "peeling
- Figs. 13a and 13b are drawings of an example of a disposable, unit
- Fig. 13c is a schematic partial cross-section of the round inlet 50 as herinafter described. Said system
- Said container has an enlarged lower end 140 closed by a peel off film
- a special plunger 142 is placed within the tubular container and
- liquid vehicle liquid vehicle, solvent or activating medium gel.
- solvent or activating medium gel On its top there is a
- tubular container 39 and covered with a peel off film 51, and an inner ledge or a groove 52 in the inner surface of said port that engages the
- the quantity of the debriding agent and the solvent vehicle may be any quantity of the debriding agent and the solvent vehicle.
- the tubular container is
- the pressing surface is releasing into a cross bar
- container may be an integral part of the vehicle container (inside or outside) with the plunger system designed to open the communication
- the invention can be carried out using a variety of systems and means,
- This preparatory set is designed to provide specific means for the treatment
- treatment is to preserve as much as possible of the living tissues in the harsh conditions of a traumatized skin with impaired local circulation at the
- the set that provides the protective micro-environment may be composed of
- An occlusive dressing such as
- M.D.O.D. Multipurpose Dynamic Occlusive Dressing
- 4132/96 may provide all the changing, dynamic needs of the wound but a combination of different occlusive and non occlusive dressings may also
- the first needs are to
- hydrating dressings gel, soaking dressing, ointments or creams may be
- occlusive chamber increases the efficacy and the bioactivity of the various
- the M.D.O.D allows a minute control of the occlusive chamber ambient and its continuing changes
- a continuous irrigation/soaking dressing A thick gauze or fibrous
- a traditional heavy gauze or knotted dressing that is soaked with desired liquids at the desired intervals.
- the debridement process is designed to produce within few hours a wound
- the debridement timing is important. The older the eschar is, more
- the macroscopic representation is of a
- the graft adheres to the debrided surface, protects it and serves as a matrix
- epithelial (epidermal keratocytes) cells For the propagation of the remaining epithelial (epidermal keratocytes) cells
- the LL. may also support the second stage of skin graft take: The neo-vascularization phase that is the anastomosis of some of the opened
- the main objective of the treatment modality is to promote
- bioassay test comprising the following steps:
- centimeters mixed depth burns where the center of at least 2x2
- centimeters are of a full thickness burn and the rest gradually bevels
- the debriding agent should have the following
- debriding composition may change from one debriding agent to
- a saline soaking dressing (such as
- the dry Debridase is apphed in unit dose of descending values.
- the unit doses may be achieved by using a unit dose debriding matrix or by
- the dry enzyme is sprinkled with 37 centigrade warm sahne (5 cc. for each
- the air may be sucked out after closure of the film. Special care is taken to
- the debrided areas are soaked as previously described for 2-4 hours. After
- this post-treatment soaking the wound is reassessed for the presence of I.L., eschar, bleeding vessels, exposed fat or deeper tissues.
- the reassessment is confirmed by a radial inscisional biopsy containing at
- the goal of the early cover is to promote a fast, spontaneous
- the early cover for the debrided wound should provide the following
- adherent surfaces provide some of the necessary condition for the
- epithelial cells will originate within the skin remnants and/or may be imported to the wound's site from other areas
- hormone growth factors apphed in the right amount and sequence is essential for an optimal epithehahzation process.
- hormone system This "hormone factory” is the epithehal cell
- Keratocyte culture Keratocyte culture, cell suspension or combined biological dressing
- the coverage set includes a biological cover with the above mentioned
- omograft (a partial thickness skin graft of human donor) in the form of
- the Ortec CCS is a semi synthetic "omograft"
- the living cells the hormones and growing factors for the Keratocytes
- Keratocytes propagation and wound healing enhancement may demand a dressing that will provide the adequate cover, support and
- autograft autogeneous skin grafting
- the late grafting set is designed to provide the means for grafting the areas that were not healed by the early debridement and enhanced heahng
- wound bed is clean without dermal or epidermal remnants that could be used as healing foci.
- the small skin grafts may be meshed and thus
- Such a cover can be used as a carrier for the meshed autograft
- a component of the late heahng process is the epithehahzation and the scar
- the heahng enhancing covers (such as the
- omograft and the Ortec CCS may serve as epithehahzation dressings but
- Such a dressing may be of the film
- medicated gauze such as the Omiderm or Opsite type
- medicated gauze such as the Omiderm or Opsite type
- debriding agents can be used, or different dressings and Keratocyte growth promoting agents can be employed, all without
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Abstract
A skin pre-healing composition, for the pre-treatment of traumatized skin, comprising an interface layer-forming effective amount of a debriding agent.
Description
COMPOSITIONSAND MEANS FOR THE TREATMENT OFBURNS AND OTHER CUTANEOUS TRAUMAS
Field of the Invention
The present invention relates to the treatment of traumatized skin. More
particularly, the invention relates to compositions and means for promoting
the heahng of skin by a suitable selective eschar removal and wound
heahng promotion.
Background of the Invention
Trauma to the skin is the commonest trauma in humans. The trauma may
be acute or chronic due to any kind of offensive physical agent (such as
thermal, chemical, pressure, shearing, degloving etc.). Due to its sudden
onset, severity, complexity, short and long term implications the cutaneous burn trauma will be used here as an example to other cutaneous traumas.
The burn is one of the most severe and dreaded traumas in the modern,
developed parts of the world, and even more so in its less developed areas.
Up to 100,000 American are severely burned each year and need
specialized, intensive burn unit facilities for their treatment. More than a
million Americans each year are treated in general surgery or other
non-speciahzed medical units. The numbers of small burns are practically
unfathomed and may be estimated to be far beyond 10,000,000 each year.
The traumatized skin (burned tissue) the eschar, may be of different depths,
including parts or the entire thickness of the skin and even other, deeper
tissues. The eschar characteristics may depend on the traumatizing agent
(thermal, chemical and electrical), the eschar's age and the conditions that
influenced the eschar since the onset of the trauma. Leaving the dead
eschar in place will extend and deepen the damage into the neighboring, originally undamaged tissues. This dead eschar will serve as a medium for bacteria growth, and a source of infection, contamination and sepsis that
may lead even to the patient's death. Some modern studies highlight the
relation between the presence of the eschar and deterioration of the general
immune and resistance systems, a phenomenon that promotes the oncoming
sepsis.
The assessment of the primary tissue damage in burns is difficult. The
burn's depth is changing from point to point and the eschar' color and
texture may be misleading even to the expert's eye. Very often the burn
depth may be determined only after few days, when the secondary damage
already extends beyond the original burn eschar. In order to prevent the
above mentioned complications, it is imperative to remove at the earliest
stage, as much as possible of the offending eschar. This removing of the
dead tissue is termed "debridement". The concept of debridement is as old as
medicine itself but its execution is extremely difficult and not free of risks.
The most obvious and direct debridement method is surgery. In small,
limited necrotic areas excision of the entire dead tissue up to healthy,
bleeding tissues is the procedure of choice. In the case of burns, because of
the large surfaces of dead eschar, a tangential excision (with the help of
special knives called dermatomes) of the dead eschar, layer after layer is
done. The excision should be carried down into the healthy intact tissue to
make sure that no trace of the dreaded eschar remains. It is estimated that up to 30% -50% of healthy tissue may be sacrificed in this procedure. This
healthy tissue, if preserved, could serve as a source for the natural heahng
processes. These surgical procedures are long, difficult, demanding of
patient's and medical resources with profuse bleeding. Surgery was and still
is the most common debridement technique but because of its cost and
implications should not be chosen lightly without a critical assessment of
each patient and each burn site.
The raw surface that is left after the thorough debridement should be
protected and covered immediately to prevent desiccation and further tissue
death. Due to the depth of the surgical debridement, grafting with
autogenous or non-autogenous grafts is practically the only answer. The
harvesting of the skin graft demands extending surgery into other healthy
skin areas intact until now. In large burns, only few and precious potential
donor sites exist. Thus, hard to find omografts or expensive (and not too
effective) synthetic skin substitutes or biological dressings are used.
Historically, the burn area was defined appropriately debrided only if it
could host a Irving skin graft. This is achieved by removal of tissue deeper
than the eschar, which results in heavy bleeding of the wounded healthy
tissue. The bleeding itself serves as the sign of appropriately debrided
wound, assuming that tissue that does not bleed heavily will not be able to support a skin graft. The severed blood vessels are the ones that will grow
into the graft and provide the necessary blood supply necessary for its
survival. The appearance of the bleeding bed and its "graftability" is crucial
in defining the debridement efficacy according to the known art. In fact, one
of the problems encountered with the chemical debridement of wounds is that some debriding agents have been known to be unsuitable for therapy,
because they did not leave a heavily bleeding tissue bed, and therefore
caused the failure of skin grafting. The appearance of the surgically
debrided tissue is typical and made of healthy dermal collagen, subdermal
tissue and vessels all transected by the tangential excision
Due to the abovementioned difficulties (of treating large traumatized body
areas of a very unstable patient, difficult diagnosis of the damage's extent,
extensive and risky surgery with immense blood loss, need for huge
quantities of grafts (that is only rarely available) there have been always a
tendency to continue a "conservative" treatment of the burned areas leaving
the burn eschar in place. If the eschar is left untreated, autolisis and
decomposition due mainly to the activities of the growing germs within the
dead eschar will lead to what was coined as "spontaneous sloughing" (not
unlike the "laudable pus" of old). Obviously this phenomenon is nothing more than an immense purulent, inflammatory reaction on large areas of
the immune compromised patient's body. The violent sepsis and inflammation process leads to propagation of tissue damage inward:
transforming second degree and partial thickness damage into a full
thickness third degree one. The sloughing phenomenon takes 2-4 weeks
while the patient is severely, and some times terminally, septic. If the
patient survives the ordeal he is left with most of the originally burned
areas completely exposed and raw or covered with granulation tissue that
eventually will evolve (even if grafted at this stage) into deforming and contracted scar tissue. In order to treat the dangerous inflammatory stage
several topical treatment modalities, using topical antiseptic or antibiotic
preparations were developed (some with rather severe side effects). Some of
these treatments do partially prevent some of the inflammatory and sepsis
problem but with a price: A severe delay of the eschar sloughing with
increase granulation/scar tissue formation and late scarring sequels and
increase in heahng time.
The idea of using a debriding enzymes or chemical agents to "dissolve" the
burn eschar and to prevent at least the severely traumatic surgical
debridement is not new. Ideally, it has been postulated that one would wish
for an ointment or other local preparation that could be easily applied, as
soon as possible on the fresh burn without extending the original trauma
and harming undamaged tissues. This ideal debriding agent should separate quickly and selectively only the damaged tissues leaving an intact
raw surface that could support a skin graft.
Many chemicals with proteolitic activity such as Salicilic acid, Benzoic acid,
Malic acid (Aserbin), Collagenase (Naridase, Santyl) , Trypsin (Trypur) and
Fibrinolysin-desoxyribonuclease (Elase) compounds were or still are in
current clinical use since the second world war. Several enzymes, of
microbacterial, vegetable or even animal origin were tested and some even
reached the market. These enzymes derives from microorganisms such as
Bacillus subtilis: Sutilains (Travase), Streptococci:
Streptokinase-streptodornase, plants such as the Papaya (Papain) or
Bromelain from the Pineapple (Debridase, Escharase, Ananain). Even
enzymes made of krill or pancreatic powder were tried. Most of these
compounds demand one or two daily dressing changes for five to ten days.
By the time the entire eschar is removed a rich granulation tissue has been
developed in many areas with a future scar and contracture formation.
Unfortunately all of them, including the newly developed ones such as
Travase and Genzyme Ananain require several daily dressing changes for
no less than five and sometimes more than twelve days. The use of these
enzymes was followed in several cases by a violent sepsis and even septic
shock probably due to bacteremia from exposure of the raw tissues to
several days old, contaminated and partially dissolved eschar. The debrided
tissue could not support an autogenous or non autogenous living graft
without an additional surgical debridement, thus, the debrided tissue
underwent a secondary damage through desiccation and exposure with a
secondary increase of the tissue necrosis.
Based on the above-mentioned data that represent the "state of the art" of
burn treatment the following choices of burn treatment protocols may be
considered to date:
1. The ages-old "conservative" supportive treatment of the eschar using
locally applied antiseptic and antibacterial preparations that results in a
late spontaneous eschar sloughing (two-four weeks), accompanied often by
sepsis and resulting in granulation tissues, the originator of heavy and
deforming scars. Once the burn is clean of the eschar and a healthy
granulation tissue has been developed, an autogenous skin should be
grafted to prevent the late sequel. The area that needs to be grafted is
usually most of the entire second and third degree burn (the second and
mixed depth burns has been transformed into deep burns through the
secondary burn propagation and infection/inflammation process).
2. The "surgical" approach that consists of a tangential excision of the
eschar that sacrifices healthy tissues and needs immediate biological
coverage and grafting to prevent transformation of the new clean raw debrided tissue into a new necrotic one. This protocol shortens hospitalization/healing time and when performed early enough may prevent
sepsis and scar contraction. The drawbacks are that the surgery is
extensive, risky, with a very heavy load on the hospital resources, faculties
and highly trained manpower. The need of an immediate grafting of the
raw debrided tissue dictates usually an autograft with an additional
increase of at least 10-15% of the exposed, denuded TBSA (Total Body
Surface Area) or a scarce and costly omograft or substitutes. Due to the
present surgical techniques the debrided area that need grafting is usually
most of the second and all the third degree burns.
Thus, in both treatment modalities the final tissues death and necrosis and
skin defect that follows is more extensive than the original traumatized
tissue.
Summarv of the Invention
It has now been found, And this is an object of the present invention, that it
is possible to provide means for treating wounds of the type described above,
without suffering from the disadvantages of the state of the art treatments.
The new treatment means are based on the discovery that both the above
mentioned traditional treatment modalities are based on two opposing
misconceptions. The first is an undertreatment, leaving the dead eschar
on the patient with all the severe, often lethal, drawbacks, complications
and sequels. The second is an overtreatment, debriding aggressively the
dead eschar but paying dearly with blood, precious healthy tissues,
dangerous procedures and the necessity of grafting immediately the
exposed, raw, debrided areas.
It is an object of the invention to provide biologically active compositions for
the debridement of dead eschar, which leave what will be termed
hereinafter an "interface layer" (LL.) between the dead, necrotic eschar and
the entirely normal unharmed (graftable) tissues. This interface layer,
achieved by a suitable enzymatic/chemical debridement, is characterized by
a rather normal looking collagen fibers and anatomical microstructure but
with very few open blood vessels (such as encountered in a surgically
debrided wound where the level of incision is entirely within the normal
tissue). The behavior of this interface layer is different compared to the
dead eschar or to the surgically debrided wound. The absence of dead,
necrotic tissue prevents secondary germ's contamination and sepsis. Its
structure does not tend to readily receive a skin graft and when applied, it
may survive only for very few days due to the first stage of "graft tack" that
is a passive serum imbibition. The second and definite stage of
neo-vascularization does not proceed as readily in the interface layer as in
the surgically debrided wounds because of the relative poverty of open blood
vessels. In surgically debrided wounds the open vessels eventually support
the graft with their host/graft direct anasthomosis or budding potential.
Otherwise, this interface layer, if protected from desiccation or heavy
contamination and treated in the correct way, exhibits a remarkable potential for a spontaneous reepithelialization and healing. Once the
epithelial remnants in the skin adnexae are given the right conditions for
proliferation and propagation, the newly debrided collagen bed provides
adequate conditions for a fast reepithelialization. Fast (less than three
weeks) epithelialization prevents the formation of the granulation tissue
that eventually develops into heavy and contracted scar tissue.
Once all the dermal remnants are epithelializated (in the cases of second or
mixed depth burns) only a small percent of the originally damaged skin
(usually part of the full thickness, deep-or third degree burns) remains to
treat. Correctly treated, by the end of second to fourth week post-burn,
most of the burn is healed by epithelialization and the few, relatively small
areas that are not epithelializated are clean, free of necrotic tissue and have
an adequate capillary bed to support and host a graft. At this stage, with
the patient's general condition improved, these areas may be grafted by
autogenous graft. Obviously, as the grafted area is rather small, the donor
site areas and the extent of the graft harvesting and grafting procedure is
very limited.
The conditions for the preservation of the newly debrided skin and provision
of the condition of fast, spontaneous epithelialization depends on the right
cover (such as the natural split thickness graft) of the row, debrided areas.
The required features of this cover are as follows:
- Readily available after debridement
- Adheres to the exposed, debrided areas
- Allows epithelial propagation along and under its structure
- Provides the right physical conditions (temperature, humidity, etc.)
for the wound heahng process
- Optionally provides also the important growth factors for wound
healing and epithelialization process.
Thus, the main advantages of the treatment made possible by the invention
are as follows:
1. Early, complete debridement of all necrotic tissues.
2. Non-traumatic, bloodless and low-risk non-surgical debridement.
3. Accurate early assessment of damage extent (depth and surface).
4. Natural fast epithelialization of most of the burn surface with
little or no scarring.
5. Grafting of only small part of the original burned area.
6. Fast epithelialization and grafting of the debrided areas prevents
scar formation.
7. Very cost effective compared to the state of the art treatment
modahties.
The clinical implications of these advantages are:
1. prevention of tissue secondary damage propagation.
2. preservation of all viable tissue components.
3. prevention of sepsis due to tissue necrosis.
4. early diagnosis of the extent of tissue damage.
5. early enhancement of "spontaneous" skin heahng wherever it is possible
by a maximum exploitation of the tissue's entire regenerative potential .
6. autogenous grafting exclusively of the remaining full thickness defects.
Thus, the present invention provides, inter alia, a skin pre-heahng
composition, for the pre-treatment of traumatized skin, comprising an
interface layer-forming effective amount and application means of a
debriding agent. The debriding agent is present in an amount and nature
that does not interfere with unharmed tissue under or around the eschar, or
induce substantial bleeding after debridement is completed. The
debridement does not harm or dissect the normal dermis or its
collagen/elastin fibers.
According to one preferred embodiment of the invention, the debriding agent
comprises one or more enzymes. In another preferred embodiment of the
invention the debriding agent is derived from pineapple. Typical debriding
agents of this kind include, e.g., Bromelain or a derivative or fraction
thereof, such as Debridase, Escharase or Ananain.
In another aspect, the invention is directed to an early coverage set for the
protection of an interface layer of a wound debrided by a composition as
described above and promotion of its heahng, comprising a protective dressing that may be provided with Keratocyte growth promoting agent(s).
According to a preferred embodiment of the invention, the Keratocyte
growth promoting agent comprises an artificial dermis. According to another
preferred embodiment of the invention, the Keratocyte growth promoting
agent comprises one or more growth hormones.
The invention further provides a method for treating a patient suffering from trauma of the skin, said method comprising the steps of:
(a) pre-treating the wound by humidification;
(b) treating the wound with a debriding agent in an amount and
for a period of time that leave the untraumatized tissues unharmed, do not promote substantial bleeding and/or contamination, and which generate an
interface layer, as defined herein;
(c) covering the debrided wound with a matrix and layer which
promotes keratocytes propagation, for a period of time sufficient to permit
spontaneous heahng of the interface layer; and
(d) grafting areas of deeper wound which were not healed through
keratocytes propagation as described in (c) above.
Preferably, but non-hmitatively, the debridement procedure is carried out
for a period of time that does not exceed 4 hours. Keratocyte propagation , in
turn, is allowed to proceed for about 2 to 4 weeks.
Other objects and advantages of the invention will become apparent as the
description proceeds.
Brief Description of the Drawings
The above and other characteristics and advantages of the invention will be
more readily apparent through the following detailed description of
preferred embodiments thereof, with reference to the appended drawings,
wherein:
Figure 1 is a photography of a fresh, mixed depth, scaled burn of the
right thigh, 2% circa TBSA. Most of the keratin bhster has been
removed, the pink-reddish periphery numbered 1 (seen in greyscale in
the figure) seems to be of a second-superficial depth. The center,
white-gray area 2 is deeper and is of a second-deep (deep-dermal)
depth.
Figure 2 is a photography of the same burn of Fig. 1 after an enzymatic
debridement (Debridase for 4 hours). The periphery of the more
superficial mid depth burn shows some small capillaries punctuate
bleeding, area 3. The central deeper area 4 shows the typical aspect of
the LL. of a second-superficial (mid depth) burn with an abundant
dermis preserved. Few punctuate bleeding vessels with no active,
intense bleeding can be seen. One may note the typical granular
aspect of the LL. due to the irregularity of the original damage: the
tissue around the skin adnexae is better preserved and the epidermal
remnants there presented are the source for the future heahng and
epithelialization process.
Figure 3 is a photography of a deep (nominal third degree) burn of the
arm and forearm. The burn was enzymatically debrided (Debridase for
4 hours). At the lateral and posterior aspect there are two islands of
non debrided tissue that shows clearly the eschar thickness and its
typical yellow-gray color where the original keratin exists (numbered
5) and white area 6 where the keratin was peeled off and only the full
thickness dermal eschar is present. The whitish areas marked 7 shows clearly a very thin LL. with its typical granular pinkish aspect and
shghtly bleeding capillaries. At the center, area marked 8 is a full
thickness burn with the viable fat and thrombosed vein that shows
under the LL. 7. At the right hand side, the elbow area numbered 9 is
of a somewhat thicker LL. and a less damaged dermis.
Figure 4 is a photography of a wider field and general appearance of
the figure 3 burn. One may see areas 5 and 6 of the non debrided
eschar, areas 7 of a deeper burn and thin preserved I.L., area 9 of a
thicker LL. (second deep or deep dermal burns) and areas 10 of a more
superficial burns, a thicker LL. with the typical punctuate capillary
bleeding similar to area 3 in Figure 2 due to the preserved dermal
papillary layer.
Figure 5 is a photography of a deep mixed flame burn (similar in
nature to the burns in Figures 3 & 4) after a formal tangential
excision. It is evident that the nature of the debrided dermis (area 11
where the blood was wiped dry) is different from the LL. It is smooth
and shiny in comparison to the rather opaque and granular nature of
the LL. The profuse bleeding of the surgically excised skin is apparent
in comparison to the sluggish, punctuate, capillary bleeding that stops
spontaneously after a few seconds.
Figure 6 is a drawing of a soaking dressing whereas 12 represents the
dressing that is of an occlusive type (such as the M.D.O.D.)or an open,
absorbent material that moisturizes the wound's surface by capillary
transfer. Container 13 represents the germ-free soaking liquids that
may be within infusion bag or other form of container connected to the
dressing by tube 14. If a vigorous soaking is required, a draining tube 15 drains the access fluids from the wounds site into a collecting
container 16.
Figure 7 is a schematic drawing representing the piglet bioassay site
(see below) whereas 17 represents the healthy, nontraumatized skin,
18 is the area of a mixed depth burn where it is more superficial at the
periphery and deeper as it approaches the center. The central area
numbered 19 is the deep, full thickness burn. The lenticular biopsy
excision 20 represents all the different areas (17, 18 and 19) of the
assay.
Figure 8 is a drawing representing the biopsy (Fig 7 no. 20) where the
different zones are represented in their cross section. Zone 21 is the
healthy skin, 22 is the rather superficial mixed (second degree) depth
burn, 23 is the deeper second degree (deep dermal) burn and 24 is the
full thickness, third degree burn.
Fig. 9 is a drawing of a unit dose debriding matrix carrier saturated with lyophihzed enzyme, with an optional rigid frame 125 made of
inert matrrials such as plastic as in figs. 10 and 11.
Fig. 10 iUustrates a placing device for the matrix carrier, with or
without the frame 225, in cross section. When pressure is applied to
the handles 41, one towards the other, possibly with one hand, the
catches 42, are moved apart from each other and the unit dose
debriding matrix carrier, 40, is released.
Fig. 11 is a drawing of a placing device for the matrix carrier in cross
section. Said device comprises a cartridge, 43, which contains one or
more unit dose debriding matrix carriers, 44, may be separated one
from the other by optional protecting disks, 25. These disks may be in
the form of a rigid frame with large openings for the passage of the
debriding agent's solvent or may be a part of the matrix carrier itself
designed to contain the debriding agent and provide rigidity when
needed. Pressure is apphed on the matrix carriers and protecting disks
towards the opening of the cartridge, by a spring, 26. A spring, 29,
applies pressure on a catch, 28, and thus said catch is held in place to
prevent the release of the disks and matrix carriers. The spring loaded
trigger, 27, is pulled and the catch is moved in such a way that either
one disk or one matrix carrier is released. Thus, a matrix carrier can be
released from a protected, sterile container and placed into an accurate
position using one hand.
Fig. 12 is a drawing of a unit dose, uniform, dispersal device in cross section. Said device comprises a cartridge, 30, which contains
Debridase or other debriding powder, 31, and a spring, 32, which
apphes pressure on a disk, 33, which transfers pressure to the
debriding powder towards the opening of the cartridge. The bottom
side of the cartridge is a flat plate, 34, movable in hnear reciprocal
motion, in the directions of arrow 35. By pulhng the spring loaded
trigger, 27, said side is moved in a full cycle, i.e. in such a way that the
"peeling blade", 36, is moved from close to side 37 to close to side 38,
and back to close to side 37. At the first half of each cycle, i.e. when
said "peeling blade" is moved from close to side 37 to close to side 38, a
uniform layer of powder, consisting a constant quantity of powder, is
"peeled" and released to the outside of the cartridge, and covers a
rectangular area beneath said cartridge with a homogeneous layer of
powder. The "peehng blade" 36 may be in the form of a "peeling
cylinder" that by turning releases a predetermined quantity of powder.
Figs. 13a and 13b are drawings of an example of a disposable, unit
dose, mixing device-system. Fig. 13c is a schematic partial cross-section of the round inlet 50 as herinafter described. Said system
comprises a tubular container 39 containing dry debriding powder.
Said container has an enlarged lower end 140 closed by a peel off film
141. A special plunger 142 is placed within the tubular container and
has an inferior extension rod 143 with two pairs of flexible,
hydrodynamic propelling stirring arms 144 (the superior) and 45 (the
inferior one). On the superior part of the plunger a handle 46 join the
plunger by a bi-directional joint 47 and to the other end of the handle
a "T" like jointed pressing cross bar 48. Another component of the system is a round container 49 for the debriding powder, aqueous or
liquid vehicle, solvent or activating medium gel. On its top there is a
round inlet port 50 that fits inside the lower extended end 140 of the
tubular container 39 and covered with a peel off film 51, and an inner
ledge or a groove 52 in the inner surface of said port that engages the
plunger 142. A second outlet port in the center of the inferior container
surface is closed with flap or cover 54. Two elastic or other kind of
chps 55 & 56 on the container's 49 external wall hold the tubular
container of the debriding powder in place.
The quantity of the debriding agent and the solvent vehicle may be
precisely predetermine. After unchpping the tubular container 39 from
the holding chps, the peel off films 141 and 51 are removed and the
extended end 140 engages the superior, inlet port 50. After
extending-straightening the handle 46 it is pressed downward by
pressing the pressing surface 48 of the cross bar and the plunger being
pressed down pushes-extracts the debriding powder from its container
into the solvent gel. The plunger reaches and locks into the groove 52
and the two pairs of the stirring arms 144 & 45 straighten up into a
straight angle (relative to the center rod 143). The tubular container is
removed over the plunger handle that is bent parallel to the gel
container top. The pressing surface is releasing into a cross bar
position thus forming with the handle a rotating stirring crank,
rotating the stirring arms with the handle thus, mixing the powder
and gel unit doses thoroughly. When the flap cover 54 is opened the
rotation of the arms propels the mixed and activates gel-powder
mixture out of the outlet port. In other configurations the powder
container may be an integral part of the vehicle container (inside or
outside) with the plunger system designed to open the communication
between the two containers, mix the components and expels the
mixture.
Detailed Description of Preferred Embodiments
The invention can be carried out using a variety of systems and means,
one of which is described hereinafter in detail for the purpose of
illustration. The different components of a system according to one
embodiment of the invention, which is useful for the new
comprehensive treatment made possible by the invention are:
1. Pre- and post- debridement sets.
2. Debridement sets.
3. Early coverage sets.
4. Late grafting sets.
5. General dressing sets.
These elements will be described in greater detail hereinafter.
1. Pre- and post-debridement preparation sets
This preparatory set is designed to provide specific means for the treatment
of the traumatized skin before and after debridement. The goal of this
treatment is to preserve as much as possible of the living tissues in the
harsh conditions of a traumatized skin with impaired local circulation at the
periphery of the dead eschar and the denuded wound's bed after the
debridement of the dead eschar.
The set that provides the protective micro-environment may be composed of
an occlusive or open, non-occlusive dressing. An occlusive dressing such as
the Multipurpose Dynamic Occlusive Dressing (M.D.O.D.), (which is the
subject of a copending patent application filed by the same apphcant herein,
on the same day as this apphcation and identified as Attorney Docket no.
4132/96) may provide all the changing, dynamic needs of the wound but a combination of different occlusive and non occlusive dressings may also
fulfill the physical and chemical needs. In principle, the first needs are to
humidify the dry, traumatized tissues (dry eschar) and to provide the
necessary moisture to the surrounding tissues. A water containing
hydrating dressings, gel, soaking dressing, ointments or creams may be
used. The use of these dressings inside the M.D.O.D. or a traditional
occlusive chamber increases the efficacy and the bioactivity of the various
components and a special attention should be paid not to surpass the
therapeutic phase and in some cases, even harming the sensitive tissues. In
the case of non-occlusive dressings the danger is usually the desiccation of
the dressing and the adjacent tissues with sometimes an adverse effect of
the increased concentration of the solutes on the wound. In such cases a
change or correction of the dressing is mandatory. The M.D.O.D allows a
minute control of the occlusive chamber ambient and its continuing changes
and electrical and ionophoretic enhancement of the process according to
need. The following alternative dressings may be used as pre and post
debridement environmental dressings.
1. An occlusive dressing as previously described.
2. A continuous irrigation/soaking dressing. A thick gauze or fibrous
knotted (Kerlix type) dressing with an irrigation tube that is imbedded in
the dressing and allows a continuos irrigation with the desired hquid (Fig
6).
3. A traditional heavy gauze or knotted dressing that is soaked with desired liquids at the desired intervals.
2. The debridement set.
The debridement process is designed to produce within few hours a wound
bed, clean of dead eschar and covered with the above mentioned interface
layer (LL.).
The debridement timing is important. The older the eschar is, more
susceptible it is to contain contaminating germs. The debridement process
(whether surgical or chemical) introduces these germs with their toxic
products into the blood stream causing bacteremia and toxemia. The longer the debridement process, the more germs and toxic materials are inoculated.
In order to prevent this bacteremia and toxemia the debridement should be
performed on the freshest possible eschar and the process should be as short
and as fast as possible.
It is seen in photo no. 2 that the LL. (numeral 4) is the first tissue layer
immediately adjacent to the traumatized tissue and is characterized by a
normal microscopic appearance of the various structures, especially the collagen fibers but most of the patent, functioning blood vessels are not
transacted by the selective debridement process. At the level that most
traumatized vessels are debrided they are still occluded by thrombi or vasoconstriction at their end. This differs from a surgically debrided tissue
where the level of transaction is within a healthy tissue and the vessels are
transacted and bleed freely (Fig. 5) until the natural or artificially assisted
hemostasis phenomenon take place. The macroscopic representation is of a
whitish layer with few (compared to a surgically debrided tissue) bleeding points (Photo nos. 2,3,4, numeral 3,4,7,8,9,10). This layer is able to support
the first imbibition phase of skin graft "take" where the exudate serum from
the raw surface nourishes the graft. In this phase the raw dermal side of
the graft adheres to the debrided surface, protects it and serves as a matrix
for the propagation of the remaining epithelial (epidermal keratocytes) cells
that survived in the skin adnexa and at the wounds perimeters. In spite of
what was said before, in many cases (especially with thin, partial thickness
skin grafts) the LL. may also support the second stage of skin graft take:
The neo-vascularization phase that is the anastomosis of some of the opened
blood vessels with some of the grafts vessels and the ingrown of capillary
endothehal buds into the graft. Meshing the graft (inserting it in a mesh
form) for expansion and drainage may also enhance the healing process.
Nevertheless, the main objective of the treatment modality is to promote
first the spontaneous healing of the wound by epithelialization and not to
graft it permanently. The autogeneous grafting procedure is reserved only
to full thickness wounds without any dermal remains that could not be
epithelialized within 2-4 weeks.
General Procedures
The specific method of producing the LL. by a chemical or enzymatic
debridement will now be fully explained through a standard in vivo,
bioassay test, comprising the following steps:
1. An anesthetized 10 kg. piglet is used for the bioassay. Its back hair
is clipped, the hair should not be shaved or dissolved with epilating
products, in order not to change the skin integrity and fine structure.
Radiant, contact and scald burns are inflicted in order to produce 5x5
centimeters mixed depth burns where the center of at least 2x2
centimeters are of a full thickness burn and the rest gradually bevels
to a superficial burn. Such burn imitates most of the clinical
conditions. Ten burns for each etiologic agent, symmetrically placed
five on each side are inflicted.
2. According to the specific debriding agent the debridement procedure
may change. The debriding agent should have the following
characteristics:
- Does not harm the healthy or untraumatized tissues.
- Does not have toxic side effects in the prescribed uses.
- Fast action (very few hours; less than 12, preferably less than 4
hours).
Throughout this specification Debridase (Bromalein) (described, e.g., in
US 4226854) is used as an example for the debriding agent, it being
understood that the invention is in no way limited to any specific
debriding agent. However, as will be appreciated by the skilled person
the amount and the concentration of the debriding agent in the
debriding composition may change from one debriding agent to
another. For this reason, the appropriate interface layer-forming
effective amount of debriding agent should be determined in each case,
using the standard test described herein, or a comparable test.
After removing epithehal blisters a saline soaking dressing (such as
previously described) is applied on the burns for two hours. After the
soaking the remaining epithehal bhsters and burned epidermis are removed
by rubbing it with a sahne wet gauze. An adherent barrier is applied
around the burns including 1 centimeter of healthy, undamaged skin as
first step for the MDOD occlusive dressing. The burn is sprinkled with
warm sahne at 37 centigrade or covered with thin layer of hydrating gel and
the dry Debridase is apphed in unit dose of descending values.
The unit doses may be achieved by using a unit dose debriding matrix or by
using unit dose powder sprinklers such as described later. It is possible to
mix a predetermine amount of dry Debridase in its hydrating gel using a
device as previously described but in this case the amount of enzyme that is
in actual contact with the eschar is hard to determine. It is important to be
able to determine the exact quantity of the debriding agent in order to find
its efficacy. When using the Debridase of US 4,226,854, an amount of 2
grams for 100 cm2 burn was used.
The dry enzyme is sprinkled with 37 centigrade warm sahne (5 cc. for each
100 cm2) covered with 25 cc. of hydrating gel. (according to U.S. 4,226,854)
and the occluding film is apphed over the adherent barrier in tight contact
with the debriding agent in order to exclude air. When using the M.D.O.D.,
the air may be sucked out after closure of the film. Special care is taken to
keep the piglet back temperature at 37 centigrade.
After 4 hours the dressings are removed, the gel and the enzyme with or
without the carrier matrix are wiped away and the treated areas are
vigorously scraped using dry gauze, 20 times for each burn. The burns are
assessed and photographed. At this stage the overdebrided areas will show
a profuse bleeding from many vessels. A bleeding from very few bleeding
vessels does not mean overdebridement. The LL. will show as whitish
layer with an pink color showing from underneath and several punctuate,
very slowly bleeding points. This will happen wherever dermis exist. At the
center, where the burn is full thickness, the exposed fat with or without bleeding vessels shows. The underdebrided burns will appear as areas with
white or gray, partially digested eschar. Between such island of undebrided
eschar several areas of LL. may exist, as represented and described in
photographs 2, 3 and 4.
The debrided areas are soaked as previously described for 2-4 hours. After
this post-treatment soaking the wound is reassessed for the presence of I.L., eschar, bleeding vessels, exposed fat or deeper tissues.
The reassessment is confirmed by a radial inscisional biopsy containing at
one end the healthy intact skin and at the other end the deepest wound at
the center of the test area as represented and described in Figs. 7 and 8. The
clinical application of the debriding set is essentially the same, using
predetermined quantities of debriding agent in occlusive dressing after
removal of the burned epithehum and blisters and soaking.
3. Early coverage set
The goal of the early cover is to promote a fast, spontaneous
epithelialization of the debrided wound by providing the optimal physical,
chemical and hormone factors needed for the remaining dermal and
epidermal components that were preserved in the debridement process.
The early cover for the debrided wound should provide the following
features:
1. Adherence: The dressing should adhere intimately to the wounds
bed in order to provide the right survival conditions for the exposed
raw tissues. The adherence preserves adequate humidity and protects
against desiccation, contamination and propagation of infection. The
adherent surfaces provide some of the necessary condition for the
Keratocytes propagation.
2. Matrix for Keratocytes (epithelial cells) propagation: The dressing
should enhance or be the matrix for the multiphcation and propagation
of the epithelial cells. These cells will originate within the skin
remnants and/or may be imported to the wound's site from other areas
of the patient (autogeneous graft) or other patients (omograft). The
natural Keratocyte's matrix is the dermis thus, any graft containing
dermis that will not provoke an immune response from the host may be
appropriate. An artificial "dermis" made of various collagen fibers may
under certain circumstances serve as such a matrix (e.g. Ortec's
Composite Cultured Skin - Ortec CCS, Integra artificial dermis etc.).
3. Wound healing and epithelialization enhancement: The right
hormone growth factors apphed in the right amount and sequence is essential for an optimal epithehahzation process. Though, many of the
factors are known and some of them even synthesized, the exact combination and sequence of the entire hormone system is still
unknown. One way to overcome this problem is to graft onto the
heahng wound an exogenous source that will produce the entire
hormone system. This "hormone factory" is the epithehal cell
(Keratocyte) itself and grafting these cells either as omograft,
Keratocyte culture, cell suspension or combined biological dressing
that contain Keratocytes and a collagen matrix may serve this purpose.
The coverage set includes a biological cover with the above mentioned
features and any necessary devices, instruments or dressings (some of these
may be part of the late grafting set). An example for such a coverage is the
omograft (a partial thickness skin graft of human donor) in the form of
plain sheathes or meshed. The Ortec CCS is a semi synthetic "omograft"
made of an artificial collagen layer (serving as a dermis) and live, donor's
Keratocytes suspension. In both cases the dressing's collagen layer provides
the physical condition for protection and heahng of the debrided wound and
the living cells the hormones and growing factors for the Keratocytes
multiphcation and propagation.
Other biological covers may include the Integra artificial dermis, Seprafilm
(Genzyme), and preparations combined with hving cells such as Dermagraft-TC, (Advanced Tissue Science -ATS; La JoUa, Ca), Cariel
(Medical Sciences Inc. Princeton, NJ), Aphgraft (Organogenesis, Canton,
MA ), Adcon-T.N. and Adcon-L (Ghatech inc. Cleveland).
The combination of the LL. and the coverage is the key for the optimal
healing process, where by the end of 2-4 weeks large parts or even most of the burn are covered by newly formed epithelium on a collagen (dermal)
foundation and the coverage remains sloughed off.
The process of Keratocytes propagation and wound healing enhancement may demand a dressing that will provide the adequate cover, support and
protection to the heahng wound but will not interfere with its dynamic
behavior. The traditional cottonwool derivatives such as the gauze provide
good cover and propagation environment but the Keratocytes and the
granulation tissue tend to grow into the fibers and fibers become imbedded
in to the heahng and growing tissues. Dressing changes besides being a
traumatic experience to patients and personnel, disrupts the heahng
process. It has been found, and this is a furthere aspect of the invention
that a silicon impregnated dressing provides all the benefits of the gauze,
without its drawbacks by not allowing the heahng tissues ingrowth.
In several cases of extensive, deep burns some areas may still show raw bed
or with the beginning of development of granulation tissue. These areas
may need an autogeneous skin grafting (autograft) for complete closure or
be left for spontaneous heahng (by secondary intention) and scarring.
4. Late grafting set.
The late grafting set is designed to provide the means for grafting the areas that were not healed by the early debridement and enhanced heahng
procedure previously described. The grafting technique and the use of devices such as prep razor/disposable dermatomes, manual or powered
dermatomes (for skin graft harvesting), manual or powered meshers is well
rooted in the daily practice of wound treatment (US 4,690,139 and patent
application PCT/IL96/00174).
As the heahng of the grafted wound depends very much on the same factors
as the enhanced heahng of the covered I.L., a similar approach may be used
here as well. Basically the wound bed is clean without dermal or epidermal
remnants that could be used as healing foci. An autograft containing
autogeneous dermis and Keratocytes is imported and spread over the
recipient bed. In cases where a large area should be covered, in order to
save healthy donor skin the small skin grafts may be meshed and thus
expanded (Patent Application PCT/IL96/00174). The heahng process and
the final results of meshed grafts are not as good as with plain sheet grafts.
The use of a heahng enhancing coverage as previously described over a
meshed autograft speeds the heahng time and the end results are much
better than without it. The use of early covers as previously described
allows the use of a very widely meshed autografts with a farther save of
donor skin. Such a cover can be used as a carrier for the meshed autograft
for an easier handhng and apphcation on the recipient site. A wound
enhancing coverage of the omograft or Ortec CCS type will serve not only as
a physical carrier and stabilizer for the meshed autograft but by performing all the roles of an early cover for a debrided wound previously mentioned,
will speed the epithehahzation of the mesh defects. A fast epithehalization
will reduce scarring and will lead to a better function and aesthetic results.
5. General dressing set.
A component of the late heahng process is the epithehahzation and the scar
modulation phenomenon. The heahng enhancing covers (such as the
omograft and the Ortec CCS) may serve as epithehahzation dressings but
they are expensive and in many cases a less costly general dressing set may
be used as dressing for the epithehalizing wound. This dressing should be
able to serve as a matrix for the epithelialization process without being
incorporated and/or interfering with it. Such a dressing may be of the film
type (such as the Omiderm or Opsite type), medicated gauze ( such as the
Sofratule or Rafuracin gauze) or the specially prepared silicon-impregnated
dressing that is part of this invention and previously described.
All the above description of preferred embodiments has been provided for
the purpose of illustration, and is not intended to limit the invention. Many
modifications can be made in the various materials and methods employed.
For instance, different debriding agents can be used, or different dressings and Keratocyte growth promoting agents can be employed, all without
exceeding the scope of the invention.
Claims
1. A skin pre-heahng composition, for the pre-treatment of traumatized
skin, comprising an interface layer-forming effective amount of a debriding
agent.
2. A composition according to claim 1, wherein the debriding agent is
present in an amount that does not substantially harm untraumatized
tissue, does not induce substantial bleeding after debridement is completed,
and does not substantially remove healthy collagen or other healthy tissues.
3. A composition according to claim 1, wherein the debriding agent
comprises one or more enzymes.
4. A composition according to claim 3, wherein the enzyme is a proteolitic enzyme.
5. A composition according to claim 3, wherein the debriding agent
comprises a material selected from among maleic acid, collagenase, Trypsin,
Fibrinolisin-desoxyribonuclease, Sutilain, Streptokinase-streptodornase,
Papain, Bromelain, Debridase, Escharase and Ananain, or a mixture of two
or more of said materials.
6. A composition according to claim 3, wherein the debriding agent is
derived from pineapple.
7. A composition according to claim 6, wherein the debriding agent is
Bromelain or a derivative or fraction thereof.
8. A composition according to claim 7, wherein the debriding agent is
Debridase or Escharase.
9. An early coverage set for promoting the heahng of an interface layer of a wound debrided by a composition of any one of claims 1 to 8, comprising a
protective dermis-like dressing made of collagen or collagen derivatives or of
human or animal dermis or dermis derivatives.
10. An early coverage set for promoting the heahng of an interface layer of a
wound debrided by a composition of any one of claims 1 to 8, comprising a
protective dressing provided with Keratocyte growth promoting agent(s).
11. A set according to claim 10, wherein the Keratocyte growth promoting
agent comprises an artificial dermis.
12. A set according to claim 10, wherein the dressing is made of a
non-autogeneous graft (omo- or zynograft).
13. A set according to claim 10, wherein the Keratocyte growth promoting
agent comprises one or more growth hormones.
14. A method for treating a patient suffering from trauma of the skin,
comprising the steps of:
(a) pre-treating the wound by humidification;
(b) treating the wound with a debriding agent in an amount and
for a period of time that do not promote substantial bleeding, and which
generate an interface layer, as defined herein;
(c) covering the debrided wound with a matrix which protects the
interface layer and promotes keratocytes propagation for a period of time
sufficient to permit spontaneous heahng of the interface layer; and
(d) grafting areas of deeper wound which were not healed through
keratocytes propagation as described in (c) above.
15. A method according to claim 14, wherein Keratocyte propagation is
allowed to proceed for about 2 to 4 weeks.
16. A method according to claim 14, wherein the debridement procedure is
carried out for a period of time that does not exceed 12 hours
17. A method according to claim 14, wherein Keratocyte propagation is
allowed to proceed for about 2 to 4 weeks.
18. An impregnated, unite, silicon gauze whereby the gauze does not
adhere to the wound and promotes Keratocyte propagation along its fibers
on the debrided wound or interface layer.
19. A unit dose debriding matrix carrier, comprising a housing containing
lyophihzed or otherwise dried debriding agent, said housing being made of
porous material so as to allow passage of the debriding agent therethrough
when a liquid is apphed thereto, said carrier further having a polygonal shape such that a plurality of identical carriers can be placed around it, to
fill a wound area.
20. A placing device for a unit dose debriding matrix carrier, comprising
elastic holding means to hold the matrix in place within the device and to
release the carrier when a light pressure is apphed on the device.
21. A device according to claim 21, which comprises a container for a
plurahty of debriding matrix carriers, and means for releasing only one
carrier each time a pressure is applied on the device.
22. A placing device for a powder debriding material comprising an
ergonomic holding handle, a powder debriding agent container and means
for activating a unit dose separation and deposition mechanism such as
peeling off an accurate quantity of the powder and releasing it on a given
surface area asepticly.
23. A unit dose powder/vehicle-carrier-gel mixing and placing device
comprising unit dose powder and vehicle containers and means for joining
said containers and mixing the countenance asepticly and extracting the
mixture onto the wound.
24. a method for treating trauma of the skin, essentially as described and
illustrated.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL12090997A IL120909A0 (en) | 1997-05-26 | 1997-05-26 | Compositions and means for the treatment of burns and other cutaneous traumas |
IL12090997 | 1997-05-26 | ||
PCT/IL1998/000237 WO1998053850A2 (en) | 1997-05-26 | 1998-05-25 | Compositions and means for the treatment of burns and other cutaneous traumas |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0983085A2 true EP0983085A2 (en) | 2000-03-08 |
Family
ID=11070172
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98921713A Withdrawn EP0983085A2 (en) | 1997-05-26 | 1998-05-25 | Compositions and means for the treatment of burns and other cutaneous traumas |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0983085A2 (en) |
JP (1) | JP2002501525A (en) |
KR (1) | KR20010012952A (en) |
AU (1) | AU7448198A (en) |
IL (1) | IL120909A0 (en) |
WO (1) | WO1998053850A2 (en) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL137689A0 (en) * | 2000-08-03 | 2001-10-31 | L R Res & Dev Ltd | System for enhanced chemical debridement |
AUPR298901A0 (en) | 2001-02-07 | 2001-03-08 | McComb Foundation, Inc., The | Cell suspension preparation technique and device |
WO2003090598A2 (en) * | 2002-04-23 | 2003-11-06 | Mediwound, Ltd. | Apparatus and methods for enzymatic escharotomy in burn induced compartment syndrome |
WO2004069147A2 (en) * | 2003-02-03 | 2004-08-19 | Mediwound Ltd. | System for enhanced chemical debridement |
WO2004089406A1 (en) * | 2003-04-09 | 2004-10-21 | Harold Armando Gomez Torres | Topical composition in the form of a gel for treating skin burns |
EP2292257A3 (en) * | 2004-07-13 | 2011-06-22 | Mediwound, Ltd. | Compositions and methods for dermatological wound healing |
CA2739243C (en) * | 2008-10-02 | 2017-08-22 | L.R.R.& D. Ltd. | Wound dressing comprising polymeric foam matrix and a hydrophilic polysaccharide disposed therein |
AU2013205148B2 (en) | 2013-03-14 | 2014-10-30 | AVITA Medical Americas, LLC | Systems and methods for tissue processing and preparation of cell suspension therefrom |
IL256675A (en) * | 2017-12-31 | 2018-02-28 | Technion Res & Development Found Ltd | Methods and compositions for prevention and treatment of pressure ulcers |
US10883084B2 (en) | 2018-10-05 | 2021-01-05 | Xenotherapeutics, Inc. | Personalized cells, tissues, and organs for transplantation from a humanized, bespoke, designated-pathogen free, (non-human) donor and methods and products relating to same |
JP7431837B2 (en) | 2018-10-05 | 2024-02-15 | ゼノセラピューティクス インコーポレイテッド | Xenograft products and methods |
WO2020198397A1 (en) | 2019-03-25 | 2020-10-01 | Xenotherapeutics, Inc. | Personalized cells, tissues, and organs for transplantation from a humanized, bespoke, designated-pathogen free, (non- human) donor and methods and products relating to same |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0040862A1 (en) * | 1979-01-11 | 1981-12-02 | Key Pharmaceuticals, Inc. | Burn matrix, method of its preparation and delivery device comprising said matrix |
US4668228A (en) * | 1985-03-12 | 1987-05-26 | Johnson & Johnson Products, Inc. | Debriding tape |
US4784653A (en) * | 1987-06-22 | 1988-11-15 | Johnson & Johnson Patient Care, Inc. | Absorbent adhesive dressing |
US5296222A (en) * | 1989-02-23 | 1994-03-22 | University Of Utah | Percutaneous drug delivery system |
EP0498532A1 (en) * | 1991-01-10 | 1992-08-12 | E.R. SQUIBB & SONS, INC. | Necrotic tissue debridement powder composition containing a proteolytic enzyme |
AU4104093A (en) * | 1992-04-20 | 1993-11-18 | Rufeld, Inc. | Method and compositions for treatment of pyonecrotic processes |
AU1939895A (en) * | 1994-03-01 | 1995-09-18 | E.R. Squibb & Sons, Inc. | Enzymatic debridement compositions and methods |
-
1997
- 1997-05-26 IL IL12090997A patent/IL120909A0/en unknown
-
1998
- 1998-05-25 KR KR1019997010922A patent/KR20010012952A/en not_active Application Discontinuation
- 1998-05-25 WO PCT/IL1998/000237 patent/WO1998053850A2/en not_active Application Discontinuation
- 1998-05-25 EP EP98921713A patent/EP0983085A2/en not_active Withdrawn
- 1998-05-25 AU AU74481/98A patent/AU7448198A/en not_active Abandoned
- 1998-05-25 JP JP50043299A patent/JP2002501525A/en active Pending
Non-Patent Citations (1)
Title |
---|
See references of WO9853850A2 * |
Also Published As
Publication number | Publication date |
---|---|
KR20010012952A (en) | 2001-02-26 |
WO1998053850A3 (en) | 1999-08-12 |
AU7448198A (en) | 1998-12-30 |
WO1998053850A2 (en) | 1998-12-03 |
IL120909A0 (en) | 1997-09-30 |
JP2002501525A (en) | 2002-01-15 |
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