This invention relates generally to devices for promoting closure, healing, and/or prevention of infection in burn wounds, ulcers, donor sites, bites and other shallow wounds. More particularly, this invention pertains to such devices that have a broad spectrum antibiotic effect.
The skin is an essential component of the nonspecific immune system and functions as a first barrier to pathogenic infection. Breaches in the skin, i.e., wounds, predispose the patient to infection. Thermal burns cause massive destruction of the integument as well as suppression of humoral and cellular immunity, enabling opportunistic organisms that do not generally infect a healthy person to infect a burn victim, both topically and systemically. Scratches, bites and ulcers also cause infection by allowing the introduction of microorganisms into deeper, susceptible tissues.
Each year, approximately 2.4 million Americans are burned. Physicians treat about 650,000 of the burn victims, 75,000 of these patients require hospitalization, and 12,000 die of burns. One million people each year sustain substantial temporary or permanent disabilities resulting from burn injuries. Infectious complications are the leading cause of morbidity and mortality in serious burn injury, with approximately 10,000 patients in the U.S. dying of burn-related infections each year.
When skin is damaged or missing due to burns, trauma or toxic injury, the mechanical functions of the skin must be replaced promptly to provide an environment that will optimize cellular regeneration and minimize the chance for sepsis. During this healing process, systemic immunosuppression is induced, placing the patient at greater risk for infection. Burns also predispose the affected area to infection by damaging the protective barrier function of the skin, thus allowing the entry and colonization of opportunistic organisms.
An ultimate goal of burn wound management is closure and healing of the wound. One way in which wound healing is promoted is the use of dressings to cover the wound site. An ideal dressing is one that flexibly covers the wound site and provides a barrier to infectious organisms and an environment that promotes the healing process. A preferred environment is one similar to the patient""s own skin in providing a moisture retaining, germ resistant covering while possibly stimulating the healing. Although biological dressings, e.g., porcine xenografts, have been the dressing of choice since the early 1960""s, new synthetic dressings are being introduced that have the additional benefit of being sterile. Both biological and synthetic dressings serve as temporary coverages for wounds and essentially all provide a barrier that aids in healing.
Burn wound healing has traditionally been augmented by the use of topical antibiotics. Currently, the most common antimicrobial agents used for burn victims are silver sulfadiazene cream, mafenide acetate cream, and silver nitrate, which dramatically decrease the bacterial burden of burn wounds and consequently decrease the rate of infection. These compounds, although effective, have limitations. Silver sulfadiazene is often used initially, but its value is often limited by bacterial resistance. Mafenide acetate is more broad spectrum in effect but it has negative side effects such as metabolic acidosis and hypersensitivity.
Other wounds can also be problematic for the treatment of antibiotic infection, especially wounds that are more likely to expose a subject to infectious agents (e.g., an animal bite), or wounds that are deep and/or difficult to access (e.g., puncture wounds). Animal bites, including human bites, expose the damaged tissue to a variety of pathogens that reflect the oral flora of the biting animal. Antibiotic management of wounds such as animal bites and puncture wounds is thus challenging, since the antibiotics used depend in large part on the potential pathogens that may have infected the wound. This can be especially problematic in individuals with antibiotic allergies, e.g., penicillin allergies, since treatment for these patients may require combination therapies to provide broad spectrum protection. In addition, certain animal bites, such as snake bites, also can result in severe inflammatory responses and/or tissue necrosis, which renders these bites especially prone to infection.
There is a need in the art for devices to promote healing and prevent infection in burns, bites, and other skin lesions that simultaneously provide a physical barrier and a chemical treatment for prevention of infection to aid the healing process. There is also a need for sterile methods of closure that can provide additional antibiotic protection to these wounds.
The present invention provides devices and compositions for the management of infection of topical wounds and lesions wherein the devices and compositions are given broad spectrum antibacterial properties by means of protonated/acidified nucleic acids. These modified nucleic acids may be present on the device surface, or integrated into the device or composition. Protonated/acidified nucleic acids have broad spectrum activity, i.e., are effective as bactericidal and/or bacteriostatic agents without regard to the class of bacteria, so are especially useful when identification of the infectious agent is difficult or when multiple infectious organisms are present. The nucleic acids used in the invention are protonated/acidified to give a pH when dissolved in water of less than pH 7 to about 1, more preferably less than pH 4.5 to about 1, and even more preferably less than pH 2 to about 1.
The nucleic acids of the invention may be protonated/acidified monomers or polymers. Polymers are preferably protonated/acidified oligonucleotides from 2-100 nucleotides in length. The nucleic acids of the invention may have nuclease resistant backbones, acid resistant backbones, and, in the preferred embodiment, have both acid resistant and nuclease resistant backbones.
In a first embodiment, the invention provides dressings for wounds which have protonated/acidified nucleic acids incorporated into or on the dressing to provide sterility and antibiotic activity. Such dressing may be comprised of any materials suitable for this use, e.g., polyester or acrylic mesh, and preferably, the dressings are a polyester mesh netting formed of woven multifilament polyester. Such dressing may also have a polymeric film bonded to one side of the coated solid substrate, preferably of about 0.001 inch +/xe2x88x92 about 0.0005 inch.
In another embodiment, the invention provides sutures having a coating of an effective amount of protonated/acidified nucleic acids. The preferred sutures are nonabsorbable, multifilament sutures, preferably polyester sutures. The protonated/acidified nucleic acid on the suture is preferably from about 0.1 to about 5 percent of the dry weight of the suture. The amount used will be an xe2x80x9ceffective amountxe2x80x9d meaning the amount needed to obtain the desired antibacterial effect over the period of time the dressing would be expected to be worn.
In yet another embodiment, the invention provides an adhesive composition having antibiotic properties for skin contact applications. The concentration of protonated/acidified nucleic acids in said polymer composition is about 0.1% to about 2% by weight. These adhesives contain an adhesive polymer with an effective amount of protonated/acidified nucleic acid dispersed throughout said polymer. The adhesive is preferably comprised of an acrylic polymer, and more preferably is a mixture of a low molecular weight solid acrylic polymer and a medium molecular weight solid acrylic polymer. In addition, the adhesive composition of the invention preferably has an effective amount of a tackifier.
In yet another embodiment, the invention provides wound sealants comprised of an effective amount of protonated/acidified nucleic acids, preferably about 0.1% to about 2% by weight. The wound sealant contains a fibrinogen activator in a concentration sufficient to initiate clot formation and may also contain fibrinogen and/or platelets. Preferably the fibrinogen activator is thrombin or batroxobin.
In yet another embodiment, the invention provides a skin substitute with an effective amount of protonated/acidified nucleic acids on its surface, or which has such modified nucleic acids impregnated into the skin substitute. The protonated/acidified nucleic acids in said skin substitute is preferably about 0.1% to about 2% by weight.
It is an object of the invention to provide a sterile environment for healing of wounds.
It is another object of the invention to provide methods of wound closure with additional antibiotic properties.
It is yet another object of the invention to prevent bacterial infection in burn victims.
It is another advantage of the invention that the mechanism of action of the protonated/acidified nucleic acids appears to be relatively non-specific, allowing them to be effective against any bacterium including clinically relevant pathogenic bacteria.
It is another advantage of the invention that the protonated/acidified nucleic acids are non-toxic to a subject treated with the modified nucleic acids.
It is a further advantage that the antibacterial effectiveness of protonated/acidified nucleic acids is neither length- nor sequence-dependent.
It is yet a further advantage that the protonated/acidified nucleic acids of the invention are economical to produce in large quantities, and thus are cost-effective for larger doses.
These and other objects, advantages, and features of the invention will become apparent to those persons skilled in the art upon reading the details of the antibiotic devices and formulations used in such devices as more fully described below.
USPTO Backgrounds
USPTO Backgrounds