US20040142021A1 - System and methods for local intradermal treatment - Google Patents
System and methods for local intradermal treatment Download PDFInfo
- Publication number
- US20040142021A1 US20040142021A1 US10/755,910 US75591004A US2004142021A1 US 20040142021 A1 US20040142021 A1 US 20040142021A1 US 75591004 A US75591004 A US 75591004A US 2004142021 A1 US2004142021 A1 US 2004142021A1
- Authority
- US
- United States
- Prior art keywords
- pharmaceutical composition
- drug
- dermal
- accordance
- pathogen
- 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.)
- Abandoned
Links
Images
Classifications
-
- 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
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/408—Virucides, spermicides
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- This invention relates generally to systems and methods of dermal drug and chemical delivery, and more particularly, to a system and methods for local intradermal prophylaxis and treatment of pathogens introduced by dermal injury from a known vector.
- the typical clinical course of the disease begins with innoculation through the bite of an infected tick, followed by the appearance of the distinctive, “bulls-eye” erythema migrans rash at the site of innoculation. It is believed that the spirochete initially remains localized in the skin for a period of days before multiplying to establish infection.
- Transdermal drug delivery systems are known. With such systems are used to infuse drugs systemically at a stable rate over an extended period of time of hours or days. These infusion systems, typically in the form of patches, are used, for example, to deliver compositions containing a single systemically acting drug such as nicotine, nitroglycerin, estradiol, or scopolamine.
- a single systemically acting drug such as nicotine, nitroglycerin, estradiol, or scopolamine.
- intradermal, local drug delivery for prophylactic and local treatment of infections resulting from innoculations such as bites or needle-sticks is not known.
- a system and methods for local intradermal treatment of pathogens includes a vector-specific pharmaceutical composition including drugs or chemicals, or combinations thereof, specifically targeted against a pathogen or pathogens, including bacteria, viruses, toxins, protozoa and venoms known to be carried or potentially carried by the identified vector.
- the pharmaceutical composition is applied to an area of skin surrounding the site of a dermal injury inflicted by the known vector, the dermal injury thus carrying the risk of innoculation with a pathogen or pathogens from the identified vector.
- dermal injuries include insect, snake and arthropod bites, accidental needlesticks, and abrasions.
- the pharmaceutical composition includes a drug, multidrug, chemical or multichemical combination, plus an enhancer or enhancers for facilitating the penetration and absorption of the pharmaceutical composition into the dermal layers at the site of dermal injury. More specifically, and in one aspect, the pharmaceutical composition provides local, intradermal drug concentrations which are sufficient to substantially eradicate or inhibit a pathogen while it remains localized.
- the local intradermal system and methods provide intradermal prophylaxis and treatment of innoculations during the early, localized stages of infection or envenomation.
- the system and methods can provide later, ongoing treatment against any surviving pathogens.
- the local intradermal system and methods are targeted against specific, readily identifiable vectors and their associated pathogens, and are simple to use for non-medically trained individuals.
- the system and methods are compact, lightweight and easily packed in gear such as camping gear, emergency gear and the like.
- FIG. 1 is a schematic illustration of a system and method for local intradermal prophylactic treatment of a dermal injury resulting in innoculation of a pathogen.
- FIG. 1 is a schematic illustration of an exemplary embodiment of a system 100 and method for local, intradermal prophylactic treatment of a pathogen 102 introduced by innoculation following a dermal injury 104 to skin 106 .
- dermal injury refers to any dermal injury inflicted by a known pathogen vector, and thus carrying a risk of innoculation with a known pathogen or pathogens associated with the vector.
- dermal injuries include, but are not limited to, insect, snake and arthropod bites, needlesticks, abrasions and other skin wounds.
- pathogen refers to any disease causing agent including a microorgansim such as a bacterium, virus or protozoan, any living organism such as a parasite, or any toxin or venom.
- drug or drugs refers to any pharmaceutically active agent including drugs and chemicals having an effect on identified pathogens, including microorganisms, parasitic organisms, toxins and venoms.
- system 100 includes a dermal patch 108 , to which a pharmaceutical composition (not shown) is applied.
- the pharmaceutical composition includes a single drug or chemical, or a combination of drugs or chemicals targeted against a specific pathogen or pathogens potentially introduced by a specific vector, plus an enhancer or enhancers for facilitating the penetration and absorption of the pharmaceutical composition into the dermal layers. More specifically, and in one aspect, the pharmaceutical composition is formulated to provide local, intradermal concentrations of the active drugs or chemicals which are sufficiently high to eradicate, nearly eradicate, or inhibit the pathogen within the period that it remains intradermally localized.
- system and methods are useful for both local prophylactic treatment immediately after a dermal injury carrying a risk of innoculation with an identified pathogen or pathogens has been identified, and later, ongoing treatment for any persisting localized infection or tissue injury, including treatment of symptoms such as pain or itching, and treatment of opportunistic infections.
- patch 108 is fabricated of plastic material such as that commonly used for transdermal patches for systemic infusion of the drugs nicotine and nitroglycerin, for example.
- the pharmaceutical composition is applied to one surface of patch 108 , adhesive applied to the same surface, and the surface covered with a peel-away backing.
- Patch 108 is then individually packaged in a paper, plastic or foil packet, ready to be stored for later use. Each packet identifies the indications for use of patch 108 , for example by identifying the vector and pathogen for which patch 108 is used.
- multiple patches 108 each having a different pharmaceutical composition targeted against different vectors and associated pathogens, are made available. Once an individual sustains a bite or other type of dermal injury carrying a risk of innoculation, the vector and pathogen or pathogens are identified and the vector specific patch 108 selected and applied as soon as possible to the innoculation site.
- the system and methods can be used to treat a wide range of pathogens introduced by innoculations from different vectors.
- the system and methods can be used for treating pathogens introduced by insect bites, accidental needlesticks, and venoms or toxins or other pathogens introduced from the bites of venomous or infectious arthropods and reptiles, or any pathogen introduced by innoculation through or into the skin.
- the specifically targeted pharmaceutical composition includes active drugs or chemicals chosen from several categories including, but not limited to, the following: antibiotics, antivirals, antipruritics, antihistamines, anti-inflammatories, antitoxins, antivenoms, vasoconstrictors to slow blood flow and retard dissemination of the pathogen from the innoculation site, steroids to minimize adverse dermal reactions, antibodies plus complement to inhibit the pathogen, and local anaesthetics such as lidocaine or benzocaine and topical analgesics for pain or itching
- active drugs or chemical in the pharmaceutical composition depends on the targeted vector and associated pathogen or pathogens.
- the pharmaceutical composition further includes an absorption or penetration enhancer or enhancers chosen to result in a predetermined rate of delivery of the chosen active drugs or chemicals in the pharmaceutical composition.
- Suitable absorption enhancers include, for example, dimethyl sulfoxide (DMSO), DMSO-like compounds, ethanolic compounds, pyroglutamic acid esters and other solvents or compounds known to those skilled in the pharmaceutical art which facilitate dermal penetration of the drugs or chemicals chosen for the pharmaceutical composition.
- DMSO dimethyl sulfoxide
- DMSO-like compounds ethanolic compounds
- pyroglutamic acid esters and other solvents or compounds known to those skilled in the pharmaceutical art which facilitate dermal penetration of the drugs or chemicals chosen for the pharmaceutical composition.
- the absorption enhancer chosen and the relative proportion of the absorption enhancer with respect to the active drugs or chemicals depends on the desired rate of delivery of the drugs or chemicals into the skin, which in turn depends on the targeted pathogen and time course of infection.
- the type and amount of enhancer is chosen so that a sufficiently high concentration of active drugs or chemicals is attained in the skin to treat the infection within the time period that the particular infection typically remains localized.
- the desired rate of delivery is measured in milligrams of active drugs or chemicals infused locally per hour or per day, to reach intradermal concentrations consistent with or exceeding known minimal inhibitory concentrations (MIC's) as known to those skilled in the medical and pharmaceutical arts, depending on the targeted pathogen and the drug or chemical combination used.
- MIC's minimal inhibitory concentrations
- system 100 is used to treat for Lyme borreliosis, commonly known as Lyme disease, and produced by the tick-borne spirochete Borrelia burgdorferi .
- Classic B. burgdorferi infection follows a pattern including an early, localized stage followed by a later, disseminated stage.
- the early localized stage commonly lasts for days, and subsequent to the bite is most often confirmed by the appearance of the distinctive, “bulls-eye” erythema migrans rash surrounding the site of the bite by an infected tick.
- the spirochetes remain loclized in the skin while multiplying to establish the later, disseminated infection.
- both the location of an identified tick bite and the appearance of the rash, or either one alone provide a readily visible indicator for locating the initial, localized site of B. burgdorferi infection, or potential infection.
- B. burgdorferi infection at the early, localized stage is important because the later, disseminated stage of Lyme disease produces serious symptoms such as joint swelling and arthritis, carditis, memory loss, localized paralysis, paresthesias and other symptoms of CNS involvement, and nonspecific symptoms such as severe fatigue. Further, once B. burgdorferi infection advances past the localized stage and becomes disseminated, eradication of the spirochete is much more difficult and expensive. Thus, the chances of successful treatment and prevention of morbidity and disability are greatly enhanced by catching and treating the infection at the early, localized stage.
- the method simply includes the step of applying self-adhesive patch 108 to the skin at the site of the tick bite 104 , wherein patch 108 is approximately centered over site 104 .
- patch 108 is approximately 1 cm to approximately 10 cm in diameter or width, covering an area of skin from about 0.5 cm 2 up to about 80 cm 2 .
- patch 108 is circular and has a diameter of about 1 cm to about 5 cm. In another embodiment, patch 108 is circular and has a diameter of about 1 cm.
- the size and shape of patch 108 varies with the type of innoculation and pathogen being targeted, the area of the body where the innoculation is located, the drugs or chemicals included in the pharmaceutical composition, and the timing of treatment relative to the moment of innoculation. Patch 108 is worn continuously for hours or days depending upon the concentration, half-life and efficacy of the drugs or chemicals used to treat the pathogen or toxin.
- patch 108 to apply the pharmaceutical composition has the advantage of preventing scratching at the innoculation site, thus reducing the chances of scarring and also the chances of introducing an opportunistic infection from, for example, staph or strep bacteria.
- the pharmaceutical composition for treating B. burgdorferi infection includes at least two antibiotic drugs, both effective against B. burgdorferi but with differing half-lives, one having a relatively short half life and the other a relatively long half-life.
- the drug with the shorter half-life is used to rapidly provide a high intradermal concentration of antibiotic which is sufficient to eradicate, or nearly eradicate the spirochete.
- the drug with the longer half-life is used to eradicate any spirochetes which survive to multiply despite the first, shorter-lived antibiotic.
- One suitable pharmaceutical composition includes, for example, doxycycline and azithromycin.
- the pharmaceutical composition includes doxycycline with another of the macrolide antibiotics.
- the absorption enhancer is, for example, a pyroglutamic acid ester.
- the pharmaceutical composition for treating a tick bite includes both antibiotics and antivirals, to treat simultaneously for arthrod-borne infections such as encephalitis and bacterial infection.
- tick-vectored illnesses which follow a similar pattern of localized infection after innoculation, followed by systemic infection, and can be treated using system 100 include, for example, Rocky Mountain Spotted Fever, Q-fever, Babesiosis, Tularemia, HME or HGE Ehrlichiosis, and relapsing fevers.
- the pharmaceutical composition is varied to include combinations of drugs specifically directed toward the multiple pathogens potentially introduced by the specific tick vector.
- the pharmaceutical composition includes a combination of a tetracycline class antibiotic such as doxycycline, plus a macrolide antibiotic such as azithromycin.
- a tetracycline class antibiotic such as doxycycline
- a macrolide antibiotic such as azithromycin.
- This combination provides prohylaxis against all six major North American and European, nonviral tick-borne pathogens, including those responsible for Lyme borreliosis, Rocky Mountain Spotted Fever, Tularemia, Babesiosis, and both HME and HGE Ehrlichiosis.
- the vector-specificity of the local intradermal prophylactic treatment system and methods means that they are especially suitable for addressing the growing incidence of tick-borne co-infections.
- the pharmaceutical composition targeted against the Ixodes tick which carries the pathogens responsible for causing Lyme borreliosis and HGE Ehrlichiosis
- the pharmaceutical composition includes doxycycline, trovafloxacin or a similar drug which treats for both pathogens.
- the pharmaceutical composition includes a combination of doxycycline and trovafloxacin or a similar drug.
- the pharmaceutical composition includes doxycycline and one of azithromycin, atovaquone and clindamycin, or a combination of any of these last three.
- the pharmaceutical composition includes trovafloxacin or a similar drug and azithromycin or another macrolide antibiotic.
- Azithromycin is especially suitable for use in the pharmaceutical compositions because it has a broad antimicrobial spectrum, achieves high tissue concentrations, is generally accepted as very safe, and has a relatively long half-life of several days.
- system 100 is used to treat any other pathogen which is commonly introduced through some type of innoculation of a pathogen, which is followed by a first, intradermally localized stage of infection and then a later disseminated stage.
- pathogens include bacteria, viruses, venoms, toxins, protozoa and parasites such as insects or worms.
- system 100 is used at the site of a mosquito bite to treat for mosquito-vectored malarial infection caused by protozoa.
- the pharmaceutical composition includes, for example, mefloquin or another antimalarial drug.
- the antimalarial drug is combined with an antibiotic such as, for example, doxycycline, azithromycin, or a combination thereof.
- an antibiotic such as, for example, doxycycline, azithromycin, or a combination thereof.
- the bites may be numerous enough that treatment with dermal patches may not be convenient or practical.
- system 100 is implemented as a topically applied cream, ointment or gel including the pharmaceutical composition, as described further below.
- system 100 is used to treat envenomations from bites of arhropods such as the brown recluse spider.
- the pharmaceutical composition includes a specific antivenom plus the penetration or absorption enhancer.
- system 100 is used to treat the bites of poisonous snakes, wherein the pharmaceutical composition includes a combination of drugs chosen to inhibit the action of the venom, inhibit dissemination and reduce inflammation.
- the pharmaceutical composition to treat a snake bite includes snake antivenom for the particular snake, antibodies plus complement, vasoconstrictors, an anti-inflammatory agent such as hydrocortisone, and the penetration enhancer, or any combination thereof.
- the pharmaceutical composition is varied to include other known drug or chemical therapies against a particular type of snake bite.
- accidental needlesticks known to carry the risk of infection with a virus such as the hepatitis-B virus or HIV are also treated with system 100 , wherein the pharmaceutical composition includes a suitable antiviral drug, drug combination or cocktail.
- the pharmaceutical composition includes one of the antivirals zidovudine, lamivudine, or indinavir, or antinucleic acid agents, or any combination thereof.
- the antiviral lamivudine is included.
- Needlesticks are also a potential source for accidental innoculation with the syphilis bacterium.
- a broad spectrum antibiotic such as doxycycline or ceftriaxone, or a combination thereof, is added to a pharmaceutical composition including an antiviral as detailed above.
- the pharmaceutical composition is formulated as a topically applied cream, ointment or gel which is directly applied to the local site of innoculation.
- the cream, ointment or gel includes the pharmaceutical composition in a suitable solvent or carrier such as, for example, a petrolatum or other oil-based carrier.
- a suitable solvent or carrier such as, for example, a petrolatum or other oil-based carrier.
- the cream or ointment is used in areas of hairy skin to which an adhesive patch such as patch 108 does not readily adhere, or used to apply the pharmaceutical composition in cases of involving multiple potential innoculation sites, such as cases of multiple insect bites.
- the system and methods for local intradermal treatment of pathogens, venoms or toxins provides a simple and fast way to treat potentially serious infections or envenomations before they progress beyond an early, intradermally localized stage. More specifically, the vector-specific pharmaceutical composition is targeted against specific vector-associated pathogens, toxins or venoms and locally delivers high intradermal concentrations of specific drugs or chemicals at the vector innoculation site.
- the system and methods act to eradicate or inhibit the pathogen or pathogens, and also to relieve specific symptoms such as pain, itch or swelling which are associated with an innoculation.
- the pharmaceutical composition can include a local anaesthetic, antihistamine, antipruritic, steroid, anti-inflammatory, or any combination thereof, for further pain relief and prevention of tissue damage after an innoculation or potential innoculation.
- the system and methods are simple to practice, and the system in the form of a patch, cream, gel or ointment is compact and easily packed in gear used by military personnel, volunteer workers, campers and other outdoors enthusiasts who are commonly exposed to various disease vectors and venomous animals.
- the vector-directed, prophylactic approach of system 100 toward tick-borne co-infections is especially useful because of the tendency for all tick-borne, antibiotic-sensitive pathogens to clinically present with similar non-specific symptoms such as fever, myalgia, weakness, etc. Further, no sensitive and specific diagnostic tests exist to distinguish among infections of the different pathogens. Therefore, waiting to diagnose and treat a sick, febrile patient for a single, specific tick-borne pathogen is often frustrating, expensive and inconclusive.
- the prophylactic systems and methods provide a way to avoid the costs and health problems associated with waiting to treat for a specific pathogen after an identified tick bite.
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Materials Engineering (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A system and methods for local intradermal treatment of a dermal injury carrying the risk of innoculation with an identified pathogen or pathogens carried by an identified vector is described. In one embodiment, the system includes a multidrug pharmaceutical composition specifically targeting the pathogen or pathogens known to be carried by the identified vector. The pharmaceutical composition is applied to a dermal patch, which is applied to the skin at the site of dermal injury. The pharmaceutical composition further includes an enhancer for facilitating the penetration and absorption of the pharmaceutical composition into the dermal layers. The pharmaceutical composition provides local, intradermal drug concentrations which are sufficient to substantially eradicate or inhibit a pathogen while it remains intradermally localized.
Description
- This invention relates generally to systems and methods of dermal drug and chemical delivery, and more particularly, to a system and methods for local intradermal prophylaxis and treatment of pathogens introduced by dermal injury from a known vector.
- Many disease causing agents, including bacteria, viruses, protozoans, toxins and venoms, are introduced by innoculation into or through the skin, for example by dermal injuries such as insect, spider or snake bites, other skin punctures such as needle sticks, or through abrasions. During the initial stage of infection or envenomation, many of these agents remain localized in an area within centimeters of the initial innoculation site, and only later begin to affect the body systemically. A classic example is Lyme borreliosis, commonly known as Lyme disease, produced by a tick-borne spirochete. The typical clinical course of the disease begins with innoculation through the bite of an infected tick, followed by the appearance of the distinctive, “bulls-eye” erythema migrans rash at the site of innoculation. It is believed that the spirochete initially remains localized in the skin for a period of days before multiplying to establish infection.
- In later stages of infection the spirochetes disseminate and can be found in remote skin sites, blood, cerebrospinal fluid, synovial fluid, and other tissues. Later stage Lyme disease symptoms include joint swelling and arthritis; carditis; memory loss, localized paralysis, paresthesias and other symptoms of CNS involvement; and nonspecific symptoms such as fatigue. Once this stage of infection has been reached, eradication of the spirochete and elimination of Lyme disease symptoms can prove frustratingly difficult. Systemic administration of antibiotic is the standard treatment, but even with aggressive, systemic antibiotic treatment during the early stage of the disease, the treatment failure rate for documented Lyme disease can be as high as 10%. Still, general agreement exists that the earlier and more aggressive the treatment, the better the patient outcome.
- However, aggressive treatment at the earliest stage possible, that is immediately after a feeding tick has been spotted and removed, is controversial. Many health care workers question the advisability of oral systemic, prophylactic antibiotic therapy for tick bites, which entails days or weeks of exposure to systemic antibiotics. The cost and side effects associated with so treating the enormous number of tick bites incurred each year must be weighed against the relatively small chance of actual disease transmission of an admittedly serious illness. The treatment controversy is further complicated by the fact that some other tick-vectored illnesses, particularly Rocky Mountain Spotted Fever and Ehrlichiosis, can and do kill otherwise healthy individuals, especially children. A premium therefore exists on finding a way to safely and effectively treat such infections at the earliest possible stage.
- Like Lyme borreliosis, many other diseases follow a similar pattern of locacied innoculation followed by later systemic infection. These include the other tick-vectored illnesses such as Q-fever, Babesiosis, Tularemia, and relapsing fevers, as well as Rocky Mountain Spotted Fever and Ehrlichiosis. Malarial infection by mosquito vectors follows a similar pattern, as do envenomations from bites of arthropods such as the brown recluse spider. Needlestick injuries also carry the risk of hepatitis-B, syphilis, HIV and other infections following the same pattern of initially localized infection, with devastating later stage systemic effects. As with the treatment of Lyme borreliosis, the chances of treatment success for all of these illnesses are greatly enhanced by catching and treating the infection or envenomation at the site of innoculation before systemic dissemination of the pathogen or toxin. Further, because some of these pathogens are known to remain viable in stored blood for up to about two weeks, early treatment and eradication of pathogens before they invade the circulatory system would improve the safety of the blood supply.
- The known treatments for such infections or envenomations after localized innoculation consist of an aggressive course of antibiotic or antiviral medication administered systemically. Depending on the pathogen involved and the timing of the treatment relative to the moment of innoculation, such treatments can have a high success rate. However, high systemic doses of antibiotics or antivirals frequently have side effects such as allergic reactions, severe gastrointestinal disturbance, ototoxicity, renal toxicity, pericarditis, etc. The risk of such side effects is particularly vexing in combination with the need for early and aggressive treatment in order to reduce the risk of treatment failure. Furthermore, at least in the case of the Lyme disease spirochete, aggressive systemic antibiotic treatment does not preclude survival of viable bacteria in sequestration.
- Transdermal drug delivery systems are known. With such systems are used to infuse drugs systemically at a stable rate over an extended period of time of hours or days. These infusion systems, typically in the form of patches, are used, for example, to deliver compositions containing a single systemically acting drug such as nicotine, nitroglycerin, estradiol, or scopolamine. However, the use of intradermal, local drug delivery for prophylactic and local treatment of infections resulting from innoculations such as bites or needle-sticks is not known.
- It would therefore be desirable to provide systems and methods for local, intradermal prophylaxis and treatment of innoculations. It would also be desirable to provide systems and methods which treat innoculations at the earliest stages of potential infection or envenomation. It would be further desirable to provide such systems and methods which are targeted against specific vectors. It would be still further desirable to provide such systems and methods including both early and later, ongoing treatment of innoculations. It would be yet still further desirable to provide such systems and methods which are simple to use for non-medically trained individuals.
- In an exemplary embodiment, a system and methods for local intradermal treatment of pathogens includes a vector-specific pharmaceutical composition including drugs or chemicals, or combinations thereof, specifically targeted against a pathogen or pathogens, including bacteria, viruses, toxins, protozoa and venoms known to be carried or potentially carried by the identified vector. The pharmaceutical composition is applied to an area of skin surrounding the site of a dermal injury inflicted by the known vector, the dermal injury thus carrying the risk of innoculation with a pathogen or pathogens from the identified vector. For example, such dermal injuries include insect, snake and arthropod bites, accidental needlesticks, and abrasions. The pharmaceutical composition includes a drug, multidrug, chemical or multichemical combination, plus an enhancer or enhancers for facilitating the penetration and absorption of the pharmaceutical composition into the dermal layers at the site of dermal injury. More specifically, and in one aspect, the pharmaceutical composition provides local, intradermal drug concentrations which are sufficient to substantially eradicate or inhibit a pathogen while it remains localized.
- The local intradermal system and methods provide intradermal prophylaxis and treatment of innoculations during the early, localized stages of infection or envenomation. In addition, the system and methods can provide later, ongoing treatment against any surviving pathogens. Further, the local intradermal system and methods are targeted against specific, readily identifiable vectors and their associated pathogens, and are simple to use for non-medically trained individuals. Still further, the system and methods are compact, lightweight and easily packed in gear such as camping gear, emergency gear and the like.
- FIG. 1 is a schematic illustration of a system and method for local intradermal prophylactic treatment of a dermal injury resulting in innoculation of a pathogen.
- FIG. 1 is a schematic illustration of an exemplary embodiment of a
system 100 and method for local, intradermal prophylactic treatment of apathogen 102 introduced by innoculation following adermal injury 104 toskin 106. As used herein, the term dermal injury refers to any dermal injury inflicted by a known pathogen vector, and thus carrying a risk of innoculation with a known pathogen or pathogens associated with the vector. Such dermal injuries include, but are not limited to, insect, snake and arthropod bites, needlesticks, abrasions and other skin wounds. Further, as used herein, the term pathogen refers to any disease causing agent including a microorgansim such as a bacterium, virus or protozoan, any living organism such as a parasite, or any toxin or venom. Still further, as used herein, the term drug or drugs refers to any pharmaceutically active agent including drugs and chemicals having an effect on identified pathogens, including microorganisms, parasitic organisms, toxins and venoms. - In the one embodiment,
system 100 includes adermal patch 108, to which a pharmaceutical composition (not shown) is applied. The pharmaceutical composition includes a single drug or chemical, or a combination of drugs or chemicals targeted against a specific pathogen or pathogens potentially introduced by a specific vector, plus an enhancer or enhancers for facilitating the penetration and absorption of the pharmaceutical composition into the dermal layers. More specifically, and in one aspect, the pharmaceutical composition is formulated to provide local, intradermal concentrations of the active drugs or chemicals which are sufficiently high to eradicate, nearly eradicate, or inhibit the pathogen within the period that it remains intradermally localized. In another aspect, the system and methods are useful for both local prophylactic treatment immediately after a dermal injury carrying a risk of innoculation with an identified pathogen or pathogens has been identified, and later, ongoing treatment for any persisting localized infection or tissue injury, including treatment of symptoms such as pain or itching, and treatment of opportunistic infections. - In one embodiment,
patch 108 is fabricated of plastic material such as that commonly used for transdermal patches for systemic infusion of the drugs nicotine and nitroglycerin, for example. The pharmaceutical composition is applied to one surface ofpatch 108, adhesive applied to the same surface, and the surface covered with a peel-away backing. Patch 108 is then individually packaged in a paper, plastic or foil packet, ready to be stored for later use. Each packet identifies the indications for use ofpatch 108, for example by identifying the vector and pathogen for whichpatch 108 is used. In one embodiment,multiple patches 108, each having a different pharmaceutical composition targeted against different vectors and associated pathogens, are made available. Once an individual sustains a bite or other type of dermal injury carrying a risk of innoculation, the vector and pathogen or pathogens are identified and the vectorspecific patch 108 selected and applied as soon as possible to the innoculation site. - By changing the pharmaceutical composition, the system and methods can be used to treat a wide range of pathogens introduced by innoculations from different vectors. For example, the system and methods can be used for treating pathogens introduced by insect bites, accidental needlesticks, and venoms or toxins or other pathogens introduced from the bites of venomous or infectious arthropods and reptiles, or any pathogen introduced by innoculation through or into the skin. Thus, depending on the vector, associated risk of infection or envenomation, and associated symptoms, the specifically targeted pharmaceutical composition includes active drugs or chemicals chosen from several categories including, but not limited to, the following: antibiotics, antivirals, antipruritics, antihistamines, anti-inflammatories, antitoxins, antivenoms, vasoconstrictors to slow blood flow and retard dissemination of the pathogen from the innoculation site, steroids to minimize adverse dermal reactions, antibodies plus complement to inhibit the pathogen, and local anaesthetics such as lidocaine or benzocaine and topical analgesics for pain or itching The exact combination of active drugs or chemical in the pharmaceutical composition depends on the targeted vector and associated pathogen or pathogens.
- The pharmaceutical composition further includes an absorption or penetration enhancer or enhancers chosen to result in a predetermined rate of delivery of the chosen active drugs or chemicals in the pharmaceutical composition. Suitable absorption enhancers include, for example, dimethyl sulfoxide (DMSO), DMSO-like compounds, ethanolic compounds, pyroglutamic acid esters and other solvents or compounds known to those skilled in the pharmaceutical art which facilitate dermal penetration of the drugs or chemicals chosen for the pharmaceutical composition. The absorption enhancer chosen and the relative proportion of the absorption enhancer with respect to the active drugs or chemicals depends on the desired rate of delivery of the drugs or chemicals into the skin, which in turn depends on the targeted pathogen and time course of infection. More specifically, the type and amount of enhancer is chosen so that a sufficiently high concentration of active drugs or chemicals is attained in the skin to treat the infection within the time period that the particular infection typically remains localized. Generally, the desired rate of delivery is measured in milligrams of active drugs or chemicals infused locally per hour or per day, to reach intradermal concentrations consistent with or exceeding known minimal inhibitory concentrations (MIC's) as known to those skilled in the medical and pharmaceutical arts, depending on the targeted pathogen and the drug or chemical combination used.
- In one embodiment, for example,
system 100 is used to treat for Lyme borreliosis, commonly known as Lyme disease, and produced by the tick-borne spirochete Borrelia burgdorferi. Classic B. burgdorferi infection follows a pattern including an early, localized stage followed by a later, disseminated stage. The early localized stage commonly lasts for days, and subsequent to the bite is most often confirmed by the appearance of the distinctive, “bulls-eye” erythema migrans rash surrounding the site of the bite by an infected tick. During the early localized stage, the spirochetes remain loclized in the skin while multiplying to establish the later, disseminated infection. Thus, both the location of an identified tick bite and the appearance of the rash, or either one alone, provide a readily visible indicator for locating the initial, localized site of B. burgdorferi infection, or potential infection. - Treatment ofB. burgdorferi infection at the early, localized stage is important because the later, disseminated stage of Lyme disease produces serious symptoms such as joint swelling and arthritis, carditis, memory loss, localized paralysis, paresthesias and other symptoms of CNS involvement, and nonspecific symptoms such as severe fatigue. Further, once B. burgdorferi infection advances past the localized stage and becomes disseminated, eradication of the spirochete is much more difficult and expensive. Thus, the chances of successful treatment and prevention of morbidity and disability are greatly enhanced by catching and treating the infection at the early, localized stage.
- Once a feeding tick has been spotted and carefully removed from the skin, the site of innoculation, or potential innoculation, withB. burgdorferi is readily identified by the location of the tick bite.
System 100 is then used to treat the bite and catch the potential B. burgdorferi infection at the localized stage. In the one embodiment as shown in FIG. 1, the method simply includes the step of applying self-adhesive patch 108 to the skin at the site of thetick bite 104, whereinpatch 108 is approximately centered oversite 104. In one embodiment,patch 108 is approximately 1 cm to approximately 10 cm in diameter or width, covering an area of skin from about 0.5 cm2 up to about 80 cm2. In one embodiment,patch 108 is circular and has a diameter of about 1 cm to about 5 cm. In another embodiment,patch 108 is circular and has a diameter of about 1 cm. However, the size and shape ofpatch 108 varies with the type of innoculation and pathogen being targeted, the area of the body where the innoculation is located, the drugs or chemicals included in the pharmaceutical composition, and the timing of treatment relative to the moment of innoculation.Patch 108 is worn continuously for hours or days depending upon the concentration, half-life and efficacy of the drugs or chemicals used to treat the pathogen or toxin. Use ofpatch 108 to apply the pharmaceutical composition has the advantage of preventing scratching at the innoculation site, thus reducing the chances of scarring and also the chances of introducing an opportunistic infection from, for example, staph or strep bacteria. - In one exemplary embodiment, the pharmaceutical composition for treatingB. burgdorferi infection includes at least two antibiotic drugs, both effective against B. burgdorferi but with differing half-lives, one having a relatively short half life and the other a relatively long half-life. The drug with the shorter half-life is used to rapidly provide a high intradermal concentration of antibiotic which is sufficient to eradicate, or nearly eradicate the spirochete. The drug with the longer half-life is used to eradicate any spirochetes which survive to multiply despite the first, shorter-lived antibiotic. One suitable pharmaceutical composition includes, for example, doxycycline and azithromycin. In alternative embodiments, the pharmaceutical composition includes doxycycline with another of the macrolide antibiotics. The absorption enhancer is, for example, a pyroglutamic acid ester. In another alternative embodiment, the pharmaceutical composition for treating a tick bite includes both antibiotics and antivirals, to treat simultaneously for arthrod-borne infections such as encephalitis and bacterial infection.
- Local, intradermal administration of doxycycline which lasts for hours or days avoids the known side effects and problems associated with a longer term of systemic administration of doxycycline or other tetracyclines. Such problems include staining of teeth and dentition problems, especially in the very young. Further, the local, intradermal administration of such antibiotics is prophylactic and effective against several tick-vectored illnesses, including the sometimes fatal HME or HGE Ehrlichiosis. Other tick-vectored illnesses which follow a similar pattern of localized infection after innoculation, followed by systemic infection, and can be treated using
system 100 include, for example, Rocky Mountain Spotted Fever, Q-fever, Babesiosis, Tularemia, HME or HGE Ehrlichiosis, and relapsing fevers. - For vector-specific, prophylactic treatment against more than one or all of these illnesses, the pharmaceutical composition is varied to include combinations of drugs specifically directed toward the multiple pathogens potentially introduced by the specific tick vector. In one embodiment, the pharmaceutical composition includes a combination of a tetracycline class antibiotic such as doxycycline, plus a macrolide antibiotic such as azithromycin. This combination provides prohylaxis against all six major North American and European, nonviral tick-borne pathogens, including those responsible for Lyme borreliosis, Rocky Mountain Spotted Fever, Tularemia, Babesiosis, and both HME and HGE Ehrlichiosis. Thus, the vector-specificity of the local intradermal prophylactic treatment system and methods means that they are especially suitable for addressing the growing incidence of tick-borne co-infections.
- More specifically, in one exemplary embodiment of the pharmaceutical composition targeted against the Ixodes tick which carries the pathogens responsible for causing Lyme borreliosis and HGE Ehrlichiosis, the pharmaceutical composition includes doxycycline, trovafloxacin or a similar drug which treats for both pathogens. Alternatively, the pharmaceutical composition includes a combination of doxycycline and trovafloxacin or a similar drug. In an alternative embodiment which adds prophylaxis against Babesiosis to prohylaxis against Lyme borreliosis and HGE Ehrlichiosis, the pharmaceutical composition includes doxycycline and one of azithromycin, atovaquone and clindamycin, or a combination of any of these last three. In an alternative embodiment for patients allergic to the tetracyclines, the pharmaceutical composition includes trovafloxacin or a similar drug and azithromycin or another macrolide antibiotic. Azithromycin is especially suitable for use in the pharmaceutical compositions because it has a broad antimicrobial spectrum, achieves high tissue concentrations, is generally accepted as very safe, and has a relatively long half-life of several days.
- In alternative embodiments,
system 100 is used to treat any other pathogen which is commonly introduced through some type of innoculation of a pathogen, which is followed by a first, intradermally localized stage of infection and then a later disseminated stage. Such pathogens include bacteria, viruses, venoms, toxins, protozoa and parasites such as insects or worms. For example, in one embodiment,system 100 is used at the site of a mosquito bite to treat for mosquito-vectored malarial infection caused by protozoa. In such an embodiment, the pharmaceutical composition includes, for example, mefloquin or another antimalarial drug. In alternative embodiments, the antimalarial drug is combined with an antibiotic such as, for example, doxycycline, azithromycin, or a combination thereof. In particular for mosquito bites, the bites may be numerous enough that treatment with dermal patches may not be convenient or practical. In an alternative embodiment especially suitable for such cases,system 100 is implemented as a topically applied cream, ointment or gel including the pharmaceutical composition, as described further below. - In another alternative embodiment,
system 100 is used to treat envenomations from bites of arhropods such as the brown recluse spider. For example, in one embodiment to treat a brown recluse spider bite, the pharmaceutical composition includes a specific antivenom plus the penetration or absorption enhancer. In still another alternative embodiment,system 100 is used to treat the bites of poisonous snakes, wherein the pharmaceutical composition includes a combination of drugs chosen to inhibit the action of the venom, inhibit dissemination and reduce inflammation. For example, in one embodiment the pharmaceutical composition to treat a snake bite includes snake antivenom for the particular snake, antibodies plus complement, vasoconstrictors, an anti-inflammatory agent such as hydrocortisone, and the penetration enhancer, or any combination thereof. In alternative embodiments the pharmaceutical composition is varied to include other known drug or chemical therapies against a particular type of snake bite. - In yet still other alternative embodiments, accidental needlesticks known to carry the risk of infection with a virus such as the hepatitis-B virus or HIV, are also treated with
system 100, wherein the pharmaceutical composition includes a suitable antiviral drug, drug combination or cocktail. For example, to treat an accidental needlestick with a needle previously used to treat a patient potentially infected with hepatitis-B or HIV, the pharmaceutical composition includes one of the antivirals zidovudine, lamivudine, or indinavir, or antinucleic acid agents, or any combination thereof. In one alternative embodiment especially suitable for treating against potential hepatitis B infection, the antiviral lamivudine is included. Needlesticks are also a potential source for accidental innoculation with the syphilis bacterium. In one embodiment suitable for treating against both the syphilis bacterium and viral infection, a broad spectrum antibiotic such as doxycycline or ceftriaxone, or a combination thereof, is added to a pharmaceutical composition including an antiviral as detailed above. - In alternative embodiments of
system 100, the pharmaceutical composition is formulated as a topically applied cream, ointment or gel which is directly applied to the local site of innoculation. The cream, ointment or gel includes the pharmaceutical composition in a suitable solvent or carrier such as, for example, a petrolatum or other oil-based carrier. The cream or ointment is used in areas of hairy skin to which an adhesive patch such aspatch 108 does not readily adhere, or used to apply the pharmaceutical composition in cases of involving multiple potential innoculation sites, such as cases of multiple insect bites. - The system and methods for local intradermal treatment of pathogens, venoms or toxins provides a simple and fast way to treat potentially serious infections or envenomations before they progress beyond an early, intradermally localized stage. More specifically, the vector-specific pharmaceutical composition is targeted against specific vector-associated pathogens, toxins or venoms and locally delivers high intradermal concentrations of specific drugs or chemicals at the vector innoculation site. The system and methods act to eradicate or inhibit the pathogen or pathogens, and also to relieve specific symptoms such as pain, itch or swelling which are associated with an innoculation. More specifically, in alternative embodiments the pharmaceutical composition can include a local anaesthetic, antihistamine, antipruritic, steroid, anti-inflammatory, or any combination thereof, for further pain relief and prevention of tissue damage after an innoculation or potential innoculation. Further, the system and methods are simple to practice, and the system in the form of a patch, cream, gel or ointment is compact and easily packed in gear used by military personnel, volunteer workers, campers and other outdoors enthusiasts who are commonly exposed to various disease vectors and venomous animals.
- The vector-directed, prophylactic approach of
system 100 toward tick-borne co-infections is especially useful because of the tendency for all tick-borne, antibiotic-sensitive pathogens to clinically present with similar non-specific symptoms such as fever, myalgia, weakness, etc. Further, no sensitive and specific diagnostic tests exist to distinguish among infections of the different pathogens. Therefore, waiting to diagnose and treat a sick, febrile patient for a single, specific tick-borne pathogen is often frustrating, expensive and inconclusive. The prophylactic systems and methods provide a way to avoid the costs and health problems associated with waiting to treat for a specific pathogen after an identified tick bite. - From the preceding description of various embodiments of the present invention, it is evident that the objects of the invention are attained. Although the invention has been described and illustrated in detail, it is to be clearly understood that the same is intended by way of illustration and example only and is not to be taken by way of limitation. Accordingly, the spirit and scope of the invention are to be limited only by the terms of the appended claims.
Claims (20)
1. A method for treating a dermal injury carrying a risk of innoculation with at least one known pathogen, said method comprising the step of:
providing a pharmaceutical composition comprising at least one drug in an amount sufficient to substantially reduce intradermal levels of the at least one known pathogen when applied to an area of skin surrounding the dermal injury.
2. A method in accordance with claim 1 wherein the dermal injury is caused by a vector of the known pathogen, said method further comprising the step of identifying the at least one known pathogen by identifying the vector of the at least one known pathogen
3. A method in accordance with claim 1 further comprising the step of providing the pharmaceutical composition in a form suitable for topical application to the area of skin surrounding the dermal injury.
4. A method in accordance with claim 3 wherein providing the pharmaceutical composition in a form suitable for topical application to the area of skin surrounding the dermal injury comprises the step of providing the pharmaceutical composition applied to a dermal patch.
5. A method in accordance with claim 4 further comprising the step of applying the dermal patch to the area of skin surrounding the dermal injury.
6. A method in accordance with claim 1 wherein providing the pharmaceutical composition in a form suitable for topical application to the area of skin surrounding the dermal injury comprises the step of providing the pharmaceutical composition as a topical preparation.
7. A method in accordance with claim 6 further comprising the step of applying the topical preparation to the area of skin surrounding the dermal injury.
8. A method in accordance with claim 1 wherein providing the pharmaceutical composition comprises the step of providing a pharmaceutical composition further comprising an enhancer for facilitating at least one of dermal absorption and penetration of the pharmaceutical composition.
9. A method in accordance with claim 1 wherein providing a pharmaceutical composition comprising at least one drug comprises the step of providing a pharmaceutical composition comprising at least a first drug selected from one of the antibiotics, the antivirals, the antimalarials, the antitoxins and the antivenoms.
10. A method in accordance with claim 9 wherein providing a pharmaceutical composition comprising at least one drug comprises the step of providing a pharmaceutical composition further comprising at least the first drug and a second drug, the second drug selected from one of the antibiotics, the antivirals, the antimalarials, the antitoxins, the antivenoms, the antipruritics, the anti-inflammatories, the vasoconstrictors, the steroids, antibodies and complement, the local anaesthetics, and the topical analgesics.
11. A method of using a dermal patch, said method comprising the step of applying to a surface of the dermal patch a pharmaceutical composition comprising at least one drug in an amount sufficient to substantially reduce intradermal levels of a pathogen when applied to an area of skin surrounding a dermal injury carrying a risk of innoculation with the pathogen.
12. A method in accordance with claim 11 further comprising the steps of:
providing the pharmaceutical composition; and
applying the dermal patch to the area of skin surrounding the dermal injury.
13. An intradermal drug delivery system for treating a dermal injury carrying a risk of innoculation of at least one identified pathogen, said intradermal drug delivery system comprising:
a dermal patch having a first surface;
wherein the at least one identified pathogen is identified by identifying the pathogen vector, a pharmaceutical composition applied to said first surface, said pharmaceutical composition comprising at least one drug in an amount sufficient to substantially reduce intradermal levels of the at least one identified pathogen when applied to an area of skin surrounding the dermal injury.
14. An intradermal drug delivery system in accordance with claim 13 wherein said pharmaceutical composition further comprises at least one enhancer for facilitating at least one of dermal absorption and penetration of the pharmaceutical composition.
15. An intradermal drug delivery system in accordance with claim 13 wherein said pharmaceutical composition further comprises one enhancer for facilitating at least one of dermal absorption and penetration of the pharmaceutical composition.
16. An intradermal drug delivery system in accordance with claim 13 herein said at least one drug comprises a first drug, said first drug comprising one of an antibiotic, an antiviral, an antimalarial, an antitoxin and an antivenom.
17. An intradermal drug delivery system in accordance with claim 16 wherein said at least one drug comprises said first drug and a second drug, said second drug comprising one of an antibiotic, an antiviral, an antimalarial, an antitoxin, an antivenom, an antipruritic, an anti-inflammatory, a vasoconstrictor, a steroid, an antibody and complement, a local anaesthetic, and a topical analgesic.
18. An intradermal drug delivery system in accordance with claim 17 wherein said first drug and said second drug both comprise an antibiotic, said first drug and said second drug having substantially differing half-lives.
19. An intradermal drug delivery system in accordance with claim 13 , wherein said at least one drug comprises a plurality of drugs, said pharmaceutical composition further comprising:
an enhancer for facilitating at least one of dermal absorption and penetration of the pharmaceutical composition
at least one drug for treating symptoms associated with an innoculation of the at least one identified pathogen, said at least one drug for treating symptoms comprising one of an antipruritic, an anti-inflammatory, a vasoconstrictor, a steroid, an antibody and complement, a local anaesthetic, and a topical analgesic.
20. A method for prophylactically treating tick-borne pathogens, said method comprising the step of:
providing a topical pharmaceutical composition, the topical pharmaceutical composition comprising at least one antibiotic in an amount sufficient to substantially reduce intradermal levels of the tick-borne pathogens when applied to an area of skin surrounding a tick bite.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/755,910 US20040142021A1 (en) | 1999-07-21 | 2004-01-13 | System and methods for local intradermal treatment |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/359,344 US6696078B1 (en) | 1999-07-21 | 1999-07-21 | System and methods for local intradermal treatment |
US10/755,910 US20040142021A1 (en) | 1999-07-21 | 2004-01-13 | System and methods for local intradermal treatment |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/359,344 Continuation US6696078B1 (en) | 1999-07-21 | 1999-07-21 | System and methods for local intradermal treatment |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040142021A1 true US20040142021A1 (en) | 2004-07-22 |
Family
ID=23413424
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/359,344 Expired - Fee Related US6696078B1 (en) | 1999-07-21 | 1999-07-21 | System and methods for local intradermal treatment |
US10/755,910 Abandoned US20040142021A1 (en) | 1999-07-21 | 2004-01-13 | System and methods for local intradermal treatment |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/359,344 Expired - Fee Related US6696078B1 (en) | 1999-07-21 | 1999-07-21 | System and methods for local intradermal treatment |
Country Status (3)
Country | Link |
---|---|
US (2) | US6696078B1 (en) |
AU (1) | AU6357400A (en) |
WO (1) | WO2001006854A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130289470A1 (en) * | 2010-12-24 | 2013-10-31 | Kamal Cherif Zahar | Kit for the treatment of envenomation |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6696078B1 (en) * | 1999-07-21 | 2004-02-24 | Edwin J. Masters | System and methods for local intradermal treatment |
US6723077B2 (en) | 2001-09-28 | 2004-04-20 | Hewlett-Packard Development Company, L.P. | Cutaneous administration system |
WO2007041314A2 (en) * | 2005-09-30 | 2007-04-12 | Tti Ellebeau, Inc. | Transdermal drug delivery systems, devices, and methods employing novel pharmaceutical vehicles |
AU2007327538B2 (en) * | 2006-06-16 | 2013-07-04 | Dirk Van Helden | Treatment for envenomation |
US20080193514A1 (en) * | 2006-11-02 | 2008-08-14 | Transcu Ltd. | Compostions and methods for iontophoresis delivery of active ingredients through hair follicles |
JPWO2008087803A1 (en) * | 2007-01-16 | 2010-05-06 | 国立大学法人北海道大学 | Liposome preparation for iontophoresis encapsulating antioxidant components |
JP2010187707A (en) * | 2007-06-12 | 2010-09-02 | Hokkaido Univ | Liposome preparation for iontophoresis comprising insulin encapsulated therein |
TW201026347A (en) * | 2008-09-10 | 2010-07-16 | Transcu Ltd | Apparatus and method to dispense HPC-based viscous liquids into porous substrates, e. g., continuous web-based process |
US10292387B1 (en) | 2016-10-31 | 2019-05-21 | James Dill | Tick removal ointment |
Citations (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4645502A (en) * | 1985-05-03 | 1987-02-24 | Alza Corporation | Transdermal delivery of highly ionized fat insoluble drugs |
US4762851A (en) * | 1985-11-29 | 1988-08-09 | Merck & Co., Inc. | Pyroglutamic acid esters used as dermal penetration enhancers for drugs |
US4767750A (en) * | 1985-05-07 | 1988-08-30 | L'oreal | Topical compositions intended for skin treatment containing salicylic acid derivatives |
US4895727A (en) * | 1985-05-03 | 1990-01-23 | Chemex Pharmaceuticals, Inc. | Pharmaceutical vehicles for exhancing penetration and retention in the skin |
US5240917A (en) * | 1991-04-03 | 1993-08-31 | Keimowitz Rudolph M | Suppression of thromboxane levels by percutaneous administration of aspirin |
US5414014A (en) * | 1993-04-08 | 1995-05-09 | Innova Biomed, Inc. | Methods for efficacious removal of attached, sucking antropods from human dermis |
US5460620A (en) * | 1992-07-31 | 1995-10-24 | Creative Products Resource, Inc. | Method of applying in-tandem applicator pads for transdermal delivery of a therapeutic agent |
US5543417A (en) * | 1994-10-21 | 1996-08-06 | Merck & Co., Inc. | Combination method of treating acne using 4-AZA-5α-cholestan-ones and 4-AZA-5α-androstan-ones as selective 5α-reductase inhibitors with anti-bacterial, keratolytic, or anti-inflammatory agents |
US5700457A (en) * | 1994-01-21 | 1997-12-23 | Dixon; Gary W. | Processed product for skin and hair treatment |
US5725875A (en) * | 1993-01-08 | 1998-03-10 | Microbarriers | Protective skin composition |
US5811088A (en) * | 1987-02-20 | 1998-09-22 | Emory University | Antiinfective compounds and methods of use |
US5886003A (en) * | 1996-03-25 | 1999-03-23 | Eli Lilly And Company | Methods of treating or ameliorating the symptoms of venomous bites and stings |
US5994372A (en) * | 1995-09-12 | 1999-11-30 | Regents Of The University Of California | Peripherally active anti-hyperalgesic opiates |
US6333356B1 (en) * | 1996-06-04 | 2001-12-25 | Avon Products, Inc. | Compounds for treating skin conditions |
US20020107174A1 (en) * | 1998-07-02 | 2002-08-08 | Erik J. Paus | Composition comprising endotoxin neutralizing protein and derivatives and uses thereof |
US20030212123A1 (en) * | 1997-05-05 | 2003-11-13 | Pfizer Inc. | COX-2 selective carprofen for treating pain and inflammation in dogs |
US6696078B1 (en) * | 1999-07-21 | 2004-02-24 | Edwin J. Masters | System and methods for local intradermal treatment |
-
1999
- 1999-07-21 US US09/359,344 patent/US6696078B1/en not_active Expired - Fee Related
-
2000
- 2000-07-20 WO PCT/US2000/019796 patent/WO2001006854A1/en active Application Filing
- 2000-07-20 AU AU63574/00A patent/AU6357400A/en not_active Abandoned
-
2004
- 2004-01-13 US US10/755,910 patent/US20040142021A1/en not_active Abandoned
Patent Citations (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4895727A (en) * | 1985-05-03 | 1990-01-23 | Chemex Pharmaceuticals, Inc. | Pharmaceutical vehicles for exhancing penetration and retention in the skin |
US4645502A (en) * | 1985-05-03 | 1987-02-24 | Alza Corporation | Transdermal delivery of highly ionized fat insoluble drugs |
US4767750A (en) * | 1985-05-07 | 1988-08-30 | L'oreal | Topical compositions intended for skin treatment containing salicylic acid derivatives |
US4762851A (en) * | 1985-11-29 | 1988-08-09 | Merck & Co., Inc. | Pyroglutamic acid esters used as dermal penetration enhancers for drugs |
US5811088A (en) * | 1987-02-20 | 1998-09-22 | Emory University | Antiinfective compounds and methods of use |
US5240917A (en) * | 1991-04-03 | 1993-08-31 | Keimowitz Rudolph M | Suppression of thromboxane levels by percutaneous administration of aspirin |
US5460620A (en) * | 1992-07-31 | 1995-10-24 | Creative Products Resource, Inc. | Method of applying in-tandem applicator pads for transdermal delivery of a therapeutic agent |
US5725875A (en) * | 1993-01-08 | 1998-03-10 | Microbarriers | Protective skin composition |
US5414014A (en) * | 1993-04-08 | 1995-05-09 | Innova Biomed, Inc. | Methods for efficacious removal of attached, sucking antropods from human dermis |
US5700457A (en) * | 1994-01-21 | 1997-12-23 | Dixon; Gary W. | Processed product for skin and hair treatment |
US5543417A (en) * | 1994-10-21 | 1996-08-06 | Merck & Co., Inc. | Combination method of treating acne using 4-AZA-5α-cholestan-ones and 4-AZA-5α-androstan-ones as selective 5α-reductase inhibitors with anti-bacterial, keratolytic, or anti-inflammatory agents |
US5994372A (en) * | 1995-09-12 | 1999-11-30 | Regents Of The University Of California | Peripherally active anti-hyperalgesic opiates |
US5886003A (en) * | 1996-03-25 | 1999-03-23 | Eli Lilly And Company | Methods of treating or ameliorating the symptoms of venomous bites and stings |
US6333356B1 (en) * | 1996-06-04 | 2001-12-25 | Avon Products, Inc. | Compounds for treating skin conditions |
US20030212123A1 (en) * | 1997-05-05 | 2003-11-13 | Pfizer Inc. | COX-2 selective carprofen for treating pain and inflammation in dogs |
US20020107174A1 (en) * | 1998-07-02 | 2002-08-08 | Erik J. Paus | Composition comprising endotoxin neutralizing protein and derivatives and uses thereof |
US6696078B1 (en) * | 1999-07-21 | 2004-02-24 | Edwin J. Masters | System and methods for local intradermal treatment |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130289470A1 (en) * | 2010-12-24 | 2013-10-31 | Kamal Cherif Zahar | Kit for the treatment of envenomation |
Also Published As
Publication number | Publication date |
---|---|
AU6357400A (en) | 2001-02-13 |
US6696078B1 (en) | 2004-02-24 |
WO2001006854A1 (en) | 2001-02-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Goldstein | Bite wounds and infection | |
CA2314326C (en) | Transdermal therapeutic device and method with capsaicin and capsaicin analogs | |
KR920005822B1 (en) | Synthetic resin wound pressing | |
US6696078B1 (en) | System and methods for local intradermal treatment | |
BR0316279A (en) | Organic compounds | |
EP0524987A4 (en) | Eriodictyon drug delivery systems | |
RU95101385A (en) | Products containing g-csf and tnf-binding protein | |
Guédénon et al. | Traditional treatment of Buruli ulcer in Benin | |
US20090317451A1 (en) | Pressure-sensitive adhesive for skin surface and/or transdermal substance delivery | |
US4450175A (en) | Method and compositions for treating acne | |
RU2686843C1 (en) | Method of treatment of combined radiation-thermal lesions and agent for implementing it | |
Campbell et al. | Therapy of hydatid disease | |
Greene | Coral snake envenomations in central and South America | |
Butler | Levamisole and immune response phenomena in cutaneous leishmaniasis | |
ES2394313T3 (en) | Transdermal formulation comprising an opioid analgesic and an aloe composition | |
KR20240012417A (en) | pain relief patches | |
Rea et al. | Ivermectin and river blindness: science and philanthropy put an end to blindly following the next generation | |
US20090022767A1 (en) | Composition, device and method for transdermal delivery of insect repellent | |
RU2221550C1 (en) | Medicinal preparation for treatment of bacterial eczema, paraproctitis, burn, trophic ulcer and other sluggish wounds and method for preparing preparation | |
RU2637092C1 (en) | Ointment for skin infections treatment | |
US8563031B2 (en) | Piroxicam-containing matrix patches and methods for the topical treatment of acute and chronic pain and inflammation therewith | |
Rubach | Management of extravasation of antineoplastic agents | |
PT1083900E (en) | USE OF OXAZOLIDIDONES FOR THE PREPARATION OF A MEDICATION FOR TRANSDERMAL DELIVERY | |
RU2770991C2 (en) | Method for preventing and treating acute radiation injury | |
EP0623351B1 (en) | Topical pharmaceutical compositions containing antianthracycline monoclonal antibodies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |