EP1827400A2 - Topical skin patch containing xanthophylls - Google Patents
Topical skin patch containing xanthophyllsInfo
- Publication number
- EP1827400A2 EP1827400A2 EP05852052A EP05852052A EP1827400A2 EP 1827400 A2 EP1827400 A2 EP 1827400A2 EP 05852052 A EP05852052 A EP 05852052A EP 05852052 A EP05852052 A EP 05852052A EP 1827400 A2 EP1827400 A2 EP 1827400A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- adhesive patch
- backing
- formulation
- adhesive
- patch
- 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- Withdrawn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
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0208—Tissues; Wipes; Patches
-
- 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
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- 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
- A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- Acne vulgaris is a chronic disorder of the pilosebaceous follicles (apparatus) characterized by comedones (blackheads), papules, pustules, cysts, nodules, and often scars, that appear on the most visible areas of the skin (e.g., the face, chest, back, neck, and upper arms).
- the pilosebaceous apparatus is largely under the control of endogenous hormones (mainly androgens) which are present in unusually high concentrations in the blood during adolescence and puberty, giving rise to an excessive production of sebum.
- the condition may worsen by a simultaneous increase in the rate of keratinization of the skin's horny layer (the stratum corneum).
- the horny cells proliferate, they can form an occlusive plug or comedone which coupled with the increased production of the sebum, represents an ideal medium for the proliferation of the skin resident strains, such as the Gram positive anaerobic bacterium, Propionibacterium acnes.
- the plugged follicles rupture and allow the discharge of their contents, causing local swelling and inflammation.
- the exposed follicles may darken from the deposition of pigment from damaged cells in the deeper layer of skin. In severe cases, acne can lead to hospitalization of the patient, extensive discomfort, and long term scarring of the skin.
- acne is treated with topical compositions in the form of creams, gels, emulsions or lotions that contain selected agents.
- agents include hormones or hormone agonists and antagonists (EP Al 0 563 813 and U.S. Patent No. 5,439,923), antimicrobial agents (U.S. Patent No. 4,446,145, GB 2,088,717, GB 2,090,135, GB 1,054,124, U.S. Patent No. 5,409,917), salicylic acid (U.S. Patent No. 4,514,385, U.S. Patent No. 4,355,028, EP Al 0 052 705, FR-A 2,581,542, and FR-A 2,607,498).
- hormones or hormone agonists and antagonists EP Al 0 563 813 and U.S. Patent No. 5,439,923
- antimicrobial agents U.S. Patent No. 4,446,145, GB 2,088,717, GB 2,090,135, GB 1,
- Oral administration of acne drugs is currently provided for severe cases of acne. These are reviewed in "Acne, A Review of Optimum Treatment” by Sykes N. I. and Webster G. F in Drugs 48, 59-70 (1994). Numerous side-effects have been described using oral administration of acne drugs. For example, isotretinoin, which is a derivative of vitamin A has associated risks of teratogenicity and may be a risk for women of childbearing age. Oral administration of antibiotics suited for treating acne may induce the appearance of adverse effects which include abdominal cramps, black tongue, cough, diarrhea, fatigue, irritation of the mouth and other undesirable symptoms.
- FDA regulations e.g., 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, April 1, 2000 Edition
- active ingredients i.e., "active ingredients"
- a select number of active ingredients that are able to treat acne, in a specified amount may be included in a composition when the composition is described as treating acne. Consequently, it is difficult to manufacture a composition that includes a topical acne drug, while at the same time maintaining (a) the solubility and stability of the active ingredients in the composition and (b) following FDA regulations.
- the device will preferably be an adhesive patch that effectively controls the rate of penetration and/or effectively controls the depth to which the ointment or gel will penetrate before solidifying.
- the device will include a known, discrete, safe, and effective amount of xanthophylls.
- the device will maintain the stability of the xanthophylls over an extended period of time.
- the device will also be convenient to use. Additionally, the device will allow for the treatment of topical skin disorders (e.g., wrinkles, skin cancer and acne), as well as the treatment of other disorders (e.g., macular degeneration, angiogenesis, cancer, heart disease, and diabetes), utilizing xanthophylls in a known, safe, efficient, and convenient manner.
- topical skin disorders e.g., wrinkles, skin cancer and acne
- other disorders e.g., macular degeneration, angiogenesis, cancer, heart disease, and diabetes
- the present invention provides for the use of an adhesive patch in preventing and/or treating topical skin disorders (e.g., wrinkles and acne), as well as the treatment of other disorders (e.g., macular degeneration, angiogenesis, cancer, heart disease, and diabetes).
- the adhesive patch includes xanthophylls in a known, discrete, safe, and effective amount.
- the adhesive patch maintains the stability of the xanthophylls over an extended period of time.
- the adhesive patch is also convenient to use.
- the present invention provides for an adhesive patch that includes a flexible backing having a front side and a back side and a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing.
- the formulation includes xanthophylls, a solvent that dissolves the xanthophylls, and a pressure sensitive adhesive.
- the present invention also provides an adhesive patch that includes a flexible backing having a front side and a back side and a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing.
- the formulation includes xanthophylls and a hot melt adhesive.
- the present invention also provides a method of locally delivering xanthophylls to a topical skin surface. The method includes topically applying to a skin surface an adhesive patch of the present invention, for a period of time effective to locally deliver xanthophylls to the topical skin surface.
- a method of systemically delivering xanthophylls to a mammal includes topically applying to a skin surface an adhesive patch of the present invention, for a period of time effective to systemically deliver xanthophylls to the mammal.
- the present invention also provides a method for treating or preventing acne or a pimple in a mammal in need thereof.
- the method includes applying to the skin surface of the mammal having the acne or the pimple or the skin surface of the mammal at risk thereof an adhesive patch of the present invention, for an effective period of time to effectively treat or prevent acne or a pimple.
- the present invention also provides a method for exfoliating the skin surface of a mammal.
- the method includes applying to the skin surface of the mammal in need of such exfoliating an adhesive patch of the present invention, for an effective period of time and removing the adhesive patch, thereby effectively exfoliating the skin surface.
- the present invention also provides a method for improving the appearance of skin surface in a mammal.
- the method includes applying to the skin surface of the mammal in need of such appearance improvement, the adhesive patch of the present invention, for an effective period of time to effectively improve the appearance of the skin surface.
- the present invention also provides an adhesive patch of the present invention for use in medical therapy.
- the present invention also provides the use of an adhesive patch of the present invention for the manufacture of a medicament for treating a topical skin condition.
- the present invention also provides the use of an adhesive patch of the present invention for the manufacture of a medicament for treating treating acne in a mammal, treating pimples in a mammal, improving the appearance of skin surface of a mammal, or any combination thereof.
- Figure 1 illustrates the front side of an adhesive patch useful in the present invention.
- Figure 2 illustrates the back side of an adhesive patch useful in the present invention.
- Figure 3 illustrates the front side of an adhesive patch useful in the present invention, with a release liner attached to the patch.
- Figure 4 illustrates the back side of an adhesive patch useful in the present invention, with a release liner attached to the patch.
- Figure 5 illustrates the back side of an adhesive patch useful in the present invention, with a release liner attached to the patch and the patch is partially detached from the release liner.
- Figure 6 illustrates the back side of an adhesive patch useful in the present invention, with a release liner attached to the patch and the patch is partially detached from the release liner.
- Figure 7 illustrates a top view of a specific patch useful in the present invention.
- Figure 8 illustrates a top view of a specific patch useful in the present invention.
- Figure 9 illustrates a specific adhesive skin patch useful in the present invention, wherein the patch is in use.
- Figure 10 illustrates an enlarged cross-sectional view of a specific patch useful in the present invention.
- the present invention provides for an adhesive patch, and for the cosmetic and pharmaceutical uses of the adhesive patch.
- the adhesive patch includes xanthophylls in a known, discrete, safe, and effective amount.
- the adhesive patch maintains the stability of the xanthophylls over an extended period of time.
- the adhesive patch is also convenient to use.
- the present invention provides a unique adhesive vehicle.
- the vehicle has pressure sensitive adhesive qualities due to its composition and viscoelastic nature.
- the adhesive is hydrophilic and therefore water can dissolve into or evaporate from the adhesive, depending on the conditions to which it is exposed.
- the relatively low occlusiveness of the adhesive skin patch can be envisioned to be a special adhesive ointment or gel which is water-breathable, such as a water washable or water soluble ointment or gel.
- the present invention provides an ointment or gel on a backing.
- the ointment or gel includes xanthophylls in a known, discrete, safe, and effective amount.
- the adhesive patch maintains the stability of the xanthophylls over an extended period of time.
- the backing is pliable and/or stretchable. Since the backing can either be porous/vapor permeable or non-porous/vapor impermeable, many consumers typically refer to the device as a "patch,” a "skin patch,” or an "adhesive skin patch.” As such, the device (i.e., the ointment or gel on the backing) will herein be referred to as a patch, a skin patch, an adhesive skin patch. It is appreciated that those skilled in the art understand that the term "patch" is used to refer to the device and is not otherwise limiting in any manner.
- xanthophylls 15 includes the singular (i.e., one xanthophyll) as well as the plural (i.e., two or more xanthophylls).
- holdout refers to the physical properties of a backing, relating to the ability of a specific class of gels or ointments to penetrate, crosslink, wet, and/or cure within the matrix of the backing.
- a specific class of gels or ointments may or may not be able to penetrate a given backing.
- the holdout properties are the ability of the gel or ointment to affect the degree of penetration, cross-linking, wetting, and/or curing within the matrix of the backing.
- Those backings with superior holdout properties will typically prevent, decrease, or lessen the likelihood of the ointment or gel from wetting the backing; will typically increase the likelihood of the ointment or gel to cross-link within the matrix of the backing; will typically increase the likelihood of the ointment or gel to cure within the matrix of the backing; and/or will typically prevent, decrease, or increase the likelihood of the ointment or gel to partially penetrate the matrix of the backing.
- a “topical acne drug” is a compound or combination of compounds that effectively prevents and/or treats acne or a pimple.
- Any suitable topical acne drug 15 can be employed, provided the topical acne drug 15 effectively treats and/or prevents acne or a pimple and the topical acne drug 15 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the patch 1.
- Suitable topical acne drugs are disclosed, e.g., in Physician's Desk
- Suitable topical acne drugs 15 include, e.g., salicylic acid, resorcinol, resorcinol acetate, calcipotriene, benzoyl peroxide, sulfur, retinol, retinoic acid, citric acid, an alpha hydroxy acid, retinal, pharmaceutically acceptable salts thereof, and combinations thereof.
- the topical acne drug 15 is salicylic acid, or a pharmaceutically acceptable salt thereof.
- retinoid refers to vitamin A or vitamin A-like compounds, including, but not limited to, retinoic acid (RA), a natural acidic derivative of vitamin A. Retinoids play a critical role in normal development, growth and differentiation by modulating the expression of target genes.
- anthralin refers to an anthraquinone (the 9, 10 quinone derivative of anthracene; anthraquinones can be made synthetically and also occur in naturally in aloe, cascara sagrada, senna, and rhubarb; the antineoplastic mitoxantrone is a synthetic derivative) derivative that reduces DNA synthesis and mitotic activity in hyperplastic epidermis, restoring the normal rate of epidermal cell proliferation and keratinization; used topically in the treatment of psoriasis and other skin conditions (also called dithranol).
- coal tar refers to a viscous black liquid containing numerous organic compounds that is obtained by the destructive distillation of coal. Coal tar can be distilled into many fractions to yield a number of useful organic products, including benzene, toluene, xylene, naphthalene, anthracene, and phenanthrene. These substances, called the coal-tar crudes, form the starting point for the synthesis of numerous products — notably dyes, drugs, explosives, flavorings, perfumes, preservatives, synthetic resins, and paints and stains. Coal tar is used medically to treat eczema, psoriasis, seborrheic dermatitis, and other skin disorders.
- salicylic acid refers to 2-hydroxybenzoic acid (C6H4(OH)CO2H), which is a colorless, crystalline organic carboxylic acid.
- Salicylic acid is used to treat many skin disorders, such as acne, dandruff, psoriasis, seborrheic dermatitis of the skin and scalp, calluses, corns, common warts, and plantar warts.
- photochemotherapy with ultraviolet A refers to a type of ultraviolet radiation treatment (phototherapy) used for severe skin diseases.
- PUVA is a combination treatment which consists of Psoralen (P) administration and then exposure of the skin to long wave ultraviolet radiation (UVA).
- Psoralens include compounds which make the skin temporarily sensitive to UVA.
- phototherapy with UVB refers to a type of radiation treatment or therapy involving exposure to ultraviolet B light (wavelength 280- 315 nm).
- “synergize” or “synergizes” or “synergistic” refers to the working together of two substances to produce an effect greater than the sum of their individual effects (www.webster-dictionary.org/definition/synergize.).
- potentiate or “potentiates” refers to the ability of one substance to make another substance (e.g., of one drug to make a second drug) effective or active or more effective or more active (http://www.ndif.org/Terms/potentiate.html).
- alleviate refers to a physical or mental lightening, lessening, eliminating or diminishing of the severity or length of time of a condition or symptom underlying the condition.
- calcipotriene refers to a synthetic topical form of vitamin D. It is involved in the growth and development of skin cells. Topical calcipotriene is used to treat plaque psoriasis (psoriasis with scaly patches). Chemically, calcipotriene is (5Z,7E, 22E,24S)-24-cyclopropyl-9,10-secochola- 5,7,10(19), 22-tetraene-l alpha, 3 beta, 24-triol-, with the empirical formula C27H40O3.
- “Therapeutically effective amount” is intended to include an amount of, e.g., xanthophylls useful in the present invention, or an amount of a topical acne drug useful in the present invention, or an amount of the combination of compounds (e.g., xanthophylls and topical acne drug), e.g., to treat the acne or to treat the symptoms of the acne in a host.
- the combination of compounds is preferably a synergistic combination.
- Synergy occurs when the effect (e.g., treatment of skin disorder) of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent.
- a synergistic effect is most clearly demonstrated at suboptimal concentrations of the compounds.
- Synergy can be in terms of lower cytotoxicity, increased activity, or some other beneficial effect of the combination compared with the individual components.
- acne refers to an inflammatory follicular, papular, or pustular eruption involving the sebaceous apparatus.
- Acne is a disease of the skin where sebaceous glands are numerous (e.g., face, upper back, and chest) and characteristic lesions are present, e.g., open (blackhead) comedo, closed (whitehead) comedo, papule, pustule, or nodule. It is believed that acne results from the thickening of the follicular opening, increased sebum production, the presence of bacteria, or the host's inflammatory response.
- the types of acne include, e.g., acne conglobata, chloracne, and rosacea.
- a "pimple” refers to a small papule, pustule, or furnacle. See, e.g., Mosby's Medical, Nursing, & Allied Health Dictionary, (5th Ed.), Mosby: St. Louis, p.1267 (1998).
- fatty acids refers to organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids can be saturated, unsaturated, or partially unsaturated.
- alfalfa refers to lucern (Medicago sativ ⁇ ).
- alpha carotene refers to a compound of the formula:
- beta carotene refers to a compound of the formula:
- Beta-carotene is a proform (prodrug) of vitamin A, and is a lipid-soluble orange pigment found in many vegetables. Beta-carotene is converted to vitamin A in the body with an efficiency of approximately 50 percent.
- vitamin A refers to a compound of the formula:
- cancer includes a type of disease caused by cells that divide and grow uncontrollably, invading and disrupting other tissues and spreading to other areas of the body (metastasis). It is an abnormal uncontrolled growth of tissue that has potential to spread to distant sites of the body. Cancer exerts its deleterious effect on the body by: (a) Destroying the surrounding adjacent tissues: e.g. compressing nerves, eroding blood vessels, or causing perforation of organs; and (b) Replacing normal functioning cells in distant sites: e.g. replacing blood forming cells in the bone marrow, replacing bones leading to increased calcium levels in the blood, or in the heart muscles so that the heart fails.
- ulcer includes a sore, often deep, sometimes inflamed, which heals slowly or not at all.
- macular degeneration includes the breakdown or damage to a portion of the retina known as the macula. Symptoms include blurring of vision (in central visual field), colors appear dim and difficulty reading or performing work up close.
- Alpha-lipoic acid provides superior antioxidant protection due to the fact that it enhances the potency of other antioxidants in the body.
- Alpha-lipoic acid may be added to the formulation 5 of the present invention if desired, in any suitable and appropriate amount.
- Phenolic compounds such oligomeric proanthocyanidins are additional useful antioxidants. Oligomeric proanthocyanidins are found naturally in grape seeds. Phenolic compounds may be added to the composition of the present invention if desired.
- the formulation 5 can further include an antibiotic.
- an "antibiotic” is any compound having activity against either Gram-positive or Gram-negative organisms (i.e., inhibits the growth or destroys the development of either Gram-positive or Gram-negative organisms). Stedman's Medical Dictionary, Illustrated. (25th Ed.), Williams & Wilkins: Baltimore (1990) and Mosbv's Medical, Nursing, & Allied Health Dictionary, (5th Ed.), Mosby: St. Louis (1998).
- Suitable antibiotics are disclosed, e.g., in Physician's Desk Reference (PDR), Medical Economics Company (Montvale, NJ), (53rd Ed.), 1999; Mayo Medical Center Formulary, Unabridged Version, Mayo Clinic (Rochester, MN), January 1998; Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals. (11th Ed.), Merck & Co., Inc.
- Suitable antibiotics include, e.g., aminoglycosides, /3-lactam antibiotics, cephalosporins, macrolides, miscellaneous antibiotics, penicillins, tetracyclines, antifungals, antimalarial agents, antituberculosis agents, antivirals, leprostatics, miscellaneous anti-infectives, quinolones, sulfonamides, urinary anti-infectives, nasal antibiotics, opthalmic antibiotics, opthalmic antivirals, opthalmic quinalones, opthalmic sulfonamides, skin and mucous membrane antibiotics, skin and mucous membrane antifungals, skin and mucous membrane antivirals, skin and mucous membrane miscellaneous anti-infectives, skin and mucous membrane scabicides and pedulicides, skin and mucous membrane antinepolasts, nitrofurans, and oxazolidinones. Physician's Desk Refernce (PDR
- Aminoglycosides include, e.g., Amikacin (amikacin sulfate); Garamycin (gentamicin sulfate); Nebcin (tobramycin sulfate); Netromycin (netilmicin sulfate); Streptomycin Sulfate; and TOBI (tobramycin).
- jS-Lactam antibiotics include, e.g., Azactam (aztreonam); Cefotan (cefotetan); Lorabid (loracarbef); Mefoxin (cefoxitin); Merrem (meropenem); and Primaxin (imipenem and cilastatin for injectable suspension).
- Cephalosporins include, e.g., Ancef (cefazolin); Ceclor (cefaclor); Cedax (ceftibuten); Cefizox (ceftizoxime sodium); Cefobid (cefoperazone sodium); Ceftin (cefuroxime axetil); Cefzil (cefprozil); Ceptaz (ceftazidime); Claforan (cefotaxime); Duricef (cefadroxil monohydrate); Fortaz (ceftazidime); Keflex (cephalexin); Keftab (cephalexin HCl); Kefurox (cefuroxime); Kefzol (cefazolin); Mandol (cefamandole nafate); Maxipime (cefepime HCl); Monocid (cefonicid sodium); Omnicef (cefdinir); Rocephin (ceftriaxone); Suprax (cefixime); Taz
- Macrolides include, e.g., Biaxin (clarithromycin); Dynabac (dirithromycin); E.E.S. 200 (Erythromycin Ethylsuccinate); E.E.S. 400 (Erythromycin Ethylsuccinate); Ery-Ped 200 (Erythromycin Ethylsuccinate); EryPed 400 (Erythromycin Ethylsuccinate); Ery-Tab (Erythromycin delayed- release tablets); Erythrocin Stearate (Erythromycin stearate); Ilosone (erythromycin estolate); PCE Dispertab (erythromycin particles in tablets); Pediazole (erythromycin ethylsuccinate and sulf ⁇ soxazole acetyl for oral suspension); Tao (troleandomycin); Zithromax (azithromycin); and Erythromycin.
- Biaxin clarithromycin
- Dynabac dirithromycin
- E.E.S. 200 Erythromycin Eth
- Miscellaneous antibiotics include, e.g., Cleocin HCl (clindamycin hydrochloride); Cleocin Phosphate (clindamycin phosphate); Coly-Mycin M (colistimethate sodium); and Vancocin HCl (vancomycin hydrochloride).
- Penicillins include, e.g., Amoxil (amoxicillin); Augmentin (amoxicillin/clavulanate potassium); Bicillin C-R 900/300 (Penicillin G benzathine and Penicillin G procaine suspension); Bicillin C-R (Penicillin G benzathine and Penicillin G procaine suspension); Bicillin L-A (Penicillin G benzathine suspension); Geocillin (carbencillin indanyl sodium); Mezlin (sterile mezlocillin sodium); Omnipen (ampicillin); Pen-Vee K (penicillin V potassium); Pfizerpen (penicillin G potassium); Pipracil (piperacillin sodium); Spectrobid (bacampicillin HCl); Ticar (ticarcillin disodium); Timentin (ticarcillin disodium and clavulanate potassium); Unasyn (ampicillin sodium/sulbactam sodium); Zosyn (piperacillin sodium and tazobactam sodium); and
- aminocycline hydrochloride Monodox (Doxycycline monohydrate capsules); Terramycin (oxytetracyline); Vectrin (minocycline hydrochloride); Vibramycin Calcium (doxycycline sodium); Vibramycin Hyclate (doxycycline hyclate); Vibramycin Monohydrate (doxycycline monohydrate); Vibra-Tabs (doxycycline hydrate); Declomycin (demeclocycline HCl); Vibrarnycin (doxycycline); Dynacin (Minocyline HCl); Terramycin (oxytetracycline HCl); Achromycin V capsules (tetracycline HCl); Lincomycins; and Cleocin HCl (clindamycin HCl).
- Antifungals include, e.g., Abelcet (amphotericin B lipid complex); AmBisome (amphotericin B); Amphotec (amphotericin B cholesterol sulfate complex); Ancobon (flucytosine); Diflucan (fluconazole); Fulvicin P/G (ultramicrosize griseofulvin); Fulvicin P/G 165 and 330 (ultramicrosize griseofulvin); Grifulvin V (griseofulvin); Gris-PEG (griseofulvin ultramicrosize); Lamisil (terbinafine hydrochloride); Nizoral (ketoconazole); Amphotericin B; Lotrimin (clotrimazole); Dapsone tablets (dapsone); Diflucan (fluconazole); Monistat-Derm cream (miconazole); Mycostatin Cream (nystatin); and Sporanox (itraconazole).
- Abelcet amphotericin B lipid complex
- Antimalarial agents include, e.g., Aralen hydrochloride (chloroquine HCl); Aralen phosphate (chloroquine phosphate); Daraprim (pyrimethamine); Lariam (mefloquine HCl); and Plaquenil (hydroxychloroquine sulfate).
- Aralen hydrochloride chloroquine HCl
- Aralen phosphate chloroquine phosphate
- Daraprim pyrimethamine
- Lariam mefloquine HCl
- Plaquenil hydroxychloroquine sulfate
- Antituberculosis agents include, e.g., Capastat sulfate (capreomycin sulfate); Myambutol (ethambutol hydrochloride); Mycobutin (rifabutin capsules); Nydrazid (isoniazid injection); Paser (aminosalicylic acid); Priftin (rifapentine); Pyrazinamide tablets (pyrazinamide); Rifadin (rifampin capsules); Rifadin IV (rifampin for injection); Rifamate (rifampin and isoniazid); Rifater (rifampin, isoniazid and pyrazinamide); Seromycin (cycloserine capsules); Streptomycin Sulfate; Tice BCG (BCG vaccine); Cycloserine (seromycin capsules); Urised (Mefhenamine); and Trecator-SC (ethionamide tablets).
- Capastat sulfate capreomycin sulfate
- Antivirals include, e.g., Alferon N (interferon alfa-n3); Crixivan (indinavir sulfate); Cytovene (ganciclovir); Cytovene-IV (ganciclovir sodium); Epivir (lamivudine); Famvir (famciclovir); Flumadine (rimantadine HCl); Foscavir (foscarnet sodium); Hivid (zalcitabine); Intron A (interferon alfa-2b); Invirase (saquinavir mesylate); Norvir (ritonavir); Rebetron combination therapy, which contains Rebetrol (ribavirin) and Intron A (inteferon alfa-2b); Rescriptor (delavirdine mesylate); Retrovir (ziduvudine); Retrovir IV
- zidovudine Symmetrel (amantadine hydrochloride); Synagis (palivizumab); Valtrex (valacyclovir HCl); Videx (didanosine); Viracept (nelfmavir mesylate); Viramune (nevirapine); Virazole (ribavirin); Vistide (cidofovir); Zerit (stavudine (d4T)); Symmetrel Syrup (amantadine HCl); Combivir Tablets (lamiduvine); and Zovirax (acyclovir).
- Leprostatics include, e.g., Dapsone Tablets (dapsone).
- Miscellaneous anti-infectives include, e.g., Daraprim (pyrimethamine); Flagyl 375 (metronidazole); Flagyl ER Tablets (metronidazole); Flagyl IV.
- Quinolones include, e.g., Cipro (ciprofloxacin HCl); Floxin (ofloxacin); Levaquin (levofloxacin); Mazaquin (lomefloxacin HCl); Noroxin (norfloxacin); Penetrex (enoxacin); Raxar (grepafloxacin HCl); Trovan (trovafloxacin mesylate); and Zagam (sparfloxacin).
- Sulfonamides include, e.g., Bactrim (trimethoprim and sulfamethoxazole); Bactrim DS (trimethoprim and sulfamethoxazole double strength); Pediazole (erythromycin ethylsuccinate and sulfisaxazole acetyl); Septra (trimethoprim and sulfamethoxazole); Septra DS (trimethoprim and sulfamethoxazole); Co-Trimoxazole, Sulfadiazine, Bactrim LV. Infusion (sulfamethoxazole); Sulfapyridine, and Pediazole (erythromycin ethylsuccinate and sulfisoxazole acetyl).
- Urinary anti-infectives include, e.g., Furadantin (nitrofurantoin); Macrobid (nitrofurantoin monohydrate macrocrystals); Macrodantin
- Nasal antibiotics include, e.g., Bactroban (mupirocin).
- Opthalmic antibiotics include, e.g., Chloromycetin opthalmic (chloramphenical); Cortisporin (neomycin and polymyxin ⁇ sulfates and hydrocortisone acetate cream); Ilotycin (erythromycin opthalmic ointment); NeoDecadron (neomycin sulfate - dexamethasone sodium phosphate); Polytrim (trimethoprim and polymyxin ⁇ sulfate opthalmic solution); Terra-Cortril (oxytetracycline HCl and hydrocortisone acetate); Terramycin (oxytetracycline); and TobraDex (tobramycin and dexamethasone opthalmic suspension and ointment).
- Chloromycetin opthalmic chloramphenical
- Cortisporin neomycin and polymyxin ⁇ sulfates and hydrocortisone acetate cream
- Ilotycin erythromycin
- Opthalmic antivirals include, e.g., Vira-A opthalmic ointment, (vidarabine).
- Opthalmic quinalones include, e.g., Chibroxin (norfloxacin opthalmic solution); Ciloxan opthalmic solution, (Ciprofloxacin HCl); Ciloxan opthalmic ointment, (Ciprofloxacin HCl); and Ocuflox opthalmic solution (ofloxacin).
- Opthalmic sulfonamides include, e.g., Blephamide opthalmic ointment (sulfacetamide sodium and prednisolone acetate); and Blephamide opthalmic suspension (sulfacetamide sodium and prednisolone acetate).
- Skin and mucous membrane antibiotics include, e.g., A/T/S (erythromycin); Bactroban (mupirocin); Benzamycin (erythromycin-benzoyl peroxide topical gel); Betadine (povidone-iodine); Cleocin T (clindamycin phosphate topical solution); Clindets (clindamycin phosphate pledgets); Cortisporin (neomycin, polymyxin B sulfates and hydrocortisone acetate cream); Emgel (erythromycin); Erycette (erythromycin topical solution); Garamycin (gentamicin sulfate); Klaron (sodium sulfacetamide lotion); Mycostatin (nystatin cream); Theramycin Z (erythromycin topical solution); T-Stat (erythromycin); Chloromycetin (chloramphenicol opthalmic ointment); Cortisporin (neomycin and polymyxin
- Skin and mucous membrane antifungals include, e.g., Exelderm (sulconazole nitrate); Fungizone (amphotericin B oral suspension); Lamisil (terbinafme hydrochloride cream); Loprox (ciclopiroxolamine); Lotrimin (clotrimazole); Lotrisone (clotrimazole and betamethasone diproprionate); Mentax (butenafme HCl); Monistat-Derm (miconazole nitrate); Mycelex (clotrimazole); Mycostatin (nystatin); Naftin (naftifme HCl); Nizoral (ketoconazole); Nystop (nystatin); Oxistat (oxiconazole nitrate); Selsun Rx (2.5% selenium sulfide lotion); and Spectazole (econazole nitrate).
- Skin and mucous membrane antivirals include, e.g., Denavir (pen
- Skin and mucous membrane miscellaneous anti-infectives include, e.g., Benzashave (benzoyl peroxide); Betadine (povidone-iodine); Betasept (chlorhexidine gluconate); Cetaphil (soap substitute); Clorpactin WCS-90 (sodium oxychlorosene); Dapsone Tablets (dapsone); Desquam-E (benzoyl peroxide); Desquam-X (benzoyl peroxide); Hibiclens (chlorhexidine gluconate); Hibistat (chlorhexidine gluconate); Impregon (tetrachlorosalicylanilide 2%); MetroCream (metronidazole); MetroGel (metronidazole); Noritate (metronidazole); pHisoHex (hexachlorophene detergent cleanser); Sulfacet-R (sodium sulfacetamide 10% and sulfur
- Skin and mucous membrane scabicides and pedulicides include, e.g., Acticin (permethrin); Elimite (permethrin); Eurax (crotamiton); and Lindane Lotion USP 1 % (lindane) .
- Skin and mucous membrane antinepolasts include, e.g., Efudex (fluorouracil); and Fluoroplex (fluorouracil).
- Nitrofurans include, e.g., Furadantin Oral Suspension (nitrofurantoin).
- Oxazolidinones include, e.g., Zyvox (linezolid).
- the antibiotic useful in the present invention is the biologically active compound present in any of the antibiotic formulations disclosed above.
- Azactam (aztreonam) is typically available as an injectable solution.
- the antibiotic is (z)-2-[[[(2-amino-4-thiazolyl) [[(2S,-3S)-2-methyl-4-oxo-l-sulfo-3- azetidinyl] carbamoyl] methylene] amino] oxy]-2-methyl propionic acid.
- Amikacin (amikacin sulfate) is commercially available from Elkins-Sinn and is D-Streptamine, O-3-amino-3-deoxy- ⁇ -D-glucopyranosyl-(l-»6)-O-6- deoxy- ⁇ -D-glucopyranosyl-(l- ⁇ 4)]-N'-(4-amino-2 hydroxy-l-oxobutyl)-2- deoxy-, (S)-, sulfate (1:2) (salt).
- Garamycin (gentamicin sulfate) is commercially available from Schering.
- Nebcin tobramycin sulfate is commercially available from Lilly and is 0-3-amino-3-deoxy-O!-D-glucopyranosyl-(l- ⁇ 4)-O-[2,6-diamino-2,3-6-trideoxy- o:-D-rz&o-hexopyranosyl-(l — > 6)]-2-deoxy-L-streptamine, sulfate (2:5) (salt).
- Netromycin (netilmicin sulfate) is commercially available from Schering and is O-3-Deoxy-4-C-methyl-3-(methylamino)-/3-L-ara-binopyranosyl (1 ⁇ 4)- O-[2,6-diamino-2,3,4,6-tetradeoxy- ⁇ ;-D-g/>'cero-liex-4-enopyranosyl-(l ⁇ '6)-2- deoxy-N 3 -ethyl-L-streptamine sulfate (2:5) salt.
- Streptomycin Sulfate is commercially available from Pfizer and is D- Streptamine, O-2-deoxy-2-(methyl amino)- ⁇ -L-glucopyranosyl-(l -»2)-O-5- deoxy-3-C-formyl- ⁇ -L-lyxofuranosyl, (l ⁇ 4)-N,N'-bis(ammoiminomethyl)-, sulfate (2:3) (salt).
- TOBI tobramycin
- Pathogenesis Corporation O-3-amino-3-deoxy-Q!-D-glucopyranosyl-(l- ⁇ 4)-O-[2,6- diamino-2,3,6-trideoxy- ⁇ -D- ⁇ o-hexopyranosyl-(l->6)]-2-deoxy-L- streptamine.
- Azactam (aztreonam) is commercially available from Bristol-Myers Squibb and is (Z)-2-[[[(2-amino-4-thiazolyl) [[(2S,-3S)-2-methyl-4-oxo-l-sulfo- 3-azetidinyl] carbamoyl] methylene] amino] oxy]-2-methylpropionic acid.
- Cefotan (cefotetan) is commercially available from Zeneca and is the disodium salt of [6R-(6 ⁇ , 7 ⁇ )]-7-[[[4-(2-amino-l-carboxy-2-oxoethylidene)-l-3, dithietan-2-yl] carbonyl] amino] -7-methoxy-3-[ [(I -methyl-lH-tetrazol-5-yl) thio] methylJ- ⁇ -oxo-S-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid.
- Lorabid (loracarbef) is commercially available from Lilly and is (6R, 7S)-7-[(R)-2-amino-2-phenylacetamido]-3-chloro-8-oxo-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, monohydrate.
- Mefoxin (cefoxitin) is commercially available from Merck and is sodium (6R, 7S)-3-(hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl) acetamido]-5- thia-1-azabicylo [4.2.0] oct-2-ene-2-carboxylate carbamate (ester).
- Merrem (meropenem) is commercially available from Zeneca and is (4R, 5S, 6S)-3-[(3S, 5S)-5-(Dimethylcarbamoyl)-3-pyrrolidinyl] thiol]-6-[(lR)-l- hydroxyethyl]-4-methyl-7-oxo-l-azabicyclo [3.2.0] hept-2-ene-2-carboxylic acid trihydrate.
- Ancef (cefazolin) is commercially available from SmithKline Beecham and is 3- ⁇ [(5-methyl-l,3,4-thiadiazol-2-yl) thio-methyl] ⁇ -8-oxo-7-[2-(lH- tetrazol-1-yl) acetamido]-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid.
- Ceclor (cefaclor) is commercially available from Lilly and is 3-chloro-7- D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid monohydrate; Cedax (ceftibuten) is commercially available from Schering and is (+)-(6R, 7R)-7-[(Z)- 2-(2-(2-amino-4-thiazoly)-4-carboxycrotonamido]-8-oxo-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, dihydrate.
- Cefizox (ceftizoxime sodium) is commercially available from Fujisawa and is sodium salt of [6R-[6 ⁇ , 7/3 (Z)]]-7 [[2, 3, dihydro-2-imino-4- thiazolyl)(methoxy amino) acetyl] amino]-8-oxo-5-thia-l-azabicyclo [4.2.0] oct- 2-ene-2-carboxyolic acid.
- Cefobid (cefoperazone sodium) is commercially available from Pfizer and is sodium (6R, 7R)-7 [(R)-2-(4-ethyl-2, 3, dioxo-1-piperazine carboxamido)- 2-(p-hydroxyphenyl)-acetamido)-3-[[(l-methyl-lH-tetrazol-5-yl) thio] methyl]- 8-oxo-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylate.
- Ceftin (cefuroxime axetil) is commercially available from Glaxo
- Cefzil (cefprozil) is commercially available from Bristol-Myers Squibb and is (6R, 7R)-7-[(R)-2-amino-2-(p-hydroxyphenyl) acetamido]-8-oxo-3- propenyl-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid monohydrate.
- Ceptaz (ceftazidime) is commercially available from Glaxo Wellcome and is l-[[7-[[(2-amino-4-thiazolyl) [(1-carboxy-l-methylethoxy) imine] acetyl] aminol-l-carboxy- ⁇ -oxo-S-thia-l-azabicyclo [4.2.0] oct-2-en-3-yl] methyl]-, hydroxide, inner salt, [6R-[6 ⁇ , 7/3 (Z)]].
- Claforan (cefotaxime) is commercially available from Hoescht Marion Roussel and is 7-[2-(2-amino-4-thiazolyl) glyoxylamido]-3-(hydroxy methyl)-8- oxo-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylate 7 2 (Z)-(O- methyloxime), acetate (ester).
- Duricef (cefadroxil monohydrate) is commercially available from Bristol-Myers Squibb and is 5-Thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7-[[amino (4-hydroxyphenyl) acetyl] amino]-3-methyl-8-oxo,- monohydrate, [6R-[6 ⁇ , 7/3 (R*)]]-.
- Keftab (cephalexin HCl) is commercially available from Dura and is 7- (D-2-Amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid hydrochloride monohydrate.
- Kefurox (cefuroxime) is commercially available from Lilly and is the sodium salt of (6R.7R) 3-carbamoyloxymethyl-7-[Z-2-methoxyimino-2-(fur-2- yl) acetamiodo] ceph-3-em-4-carboxylate.
- Kefzol (cefazolin) is commercially available from Lilly and is the sodium salt of 3- ⁇ [(5-methyl-l,3,4-thiadiazol-2-yl) thio] methyl ⁇ -8-oxo-7-[2-(lH- tetrazol-1-yl) acetamido]-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-caboxylic acid.
- Mandol (cefamandole nafate) is commercially available from Lilly and is 5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7-[[(formyloxy) phenyl acetyl] amino]-3-[[(l-methyl-lH-tetrazol-5-yl) thio] methyl] -8-oxo-, mono- sodium salt, [6R-[6 ⁇ -7/3 (R*)]].
- Maxipime (cefepime HCl) is commercially available from Bristol-Myers Squibb and is 1-[[6R, 7R)-7-[2-amino-4-thiazolyl)-glyoxylamido]-2-carboxy-8- oxo-5-thia-l-azabicyclo-[4.2.0]oct-2-en-3-yl] methyl]-l-methylpyrrolidinium chloride, 7 2 -(Z)-(O-methyloxime), monohydrochloride, monohyrate.
- Monocid (cefonicid sodium) is commercially available from SmithKline Beecham and is 5-Thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7- [(hydroxyphenyl-acety ⁇ -aminol-S-oxo-S-ttl-Csulfomethy ⁇ -lH-tetrazol-S-yl] thio] methyl]-disodium salt, [6R-[6 ⁇ , 7/3 (R*)]].
- Omnicef (cefdinir) is commercially available from Parke Davis and is
- Rocephin (ceftriaxone) is commercially available from Roche Laboratories and is (6R, 7R)-7-[2-(2-Amino-4-thiazolyl) glyoxylamido]-8-oxo- 3-[[(l ,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as-triazin-3-yl) thio] methyl]-5-thia- 1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7 2 -(Z)-O-methyloxime), disodium salt, sesquaterhydrate.
- Suprax (cefixime) is commercially available from Lederle Laboratories and is (6R, 7R)-7-[2-(2-Amino-4-thiazolyl) glyoxylamido]-8-oxo-3-vinyl-5-thia- 1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7 2 -(Z)-[O-(carboxymethyl) oxime] trihydrate.
- Tazicef (ceftazidime) is commercially available from SmithKline Beecham and is pentahydrate of Pyridinium, l-[[7-[[2-amino-4-thiazolyl) [(1- carboxy-1-methylethoxy) imino] acetyl] ammo]-2-carboxy-8-oxo-5-thia-l- azabicyclo (4.2.0) oct-2-en-3-yl] methyl] -hydroxide, inner salt, [6R, -[6a, 7/3
- Tazidime (ceftazidime) is commercially available from Lilly and is pentahydrate of Pyridinium, l-[[7-[[2-amino-4-thiazolyl) [(1-carboxy-l- methylethoxy) imino] acetyl] amino]-2-corboxy-8-oxo-5-thia-l-azabicyclo (4.2.0) oct-2-en-3-yl] methyl] -hydroxide, inner salt, [6R, -[6a, I ⁇ (Z)]].
- Vantin (ce ⁇ odoxime proxetil) is commercially available from Pharmacia & Upjohn and is (RS)-I (isopropoxycarbonyloxy) ethyl (+)-(6R, 7R)-7-[2-(2- amino-4-thiazolyl)-2- ⁇ (Z)methoxyimino ⁇ acetamido]-3-methoxymethyl-8-oxo- 5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylate.
- Zinacef (cefuroxime) is commercially available from Glaxo Wellcome and is sodium salt of (6R, 7R)-3-carbamoyloxymethyl-7-[Z-2-methoxy-imino-2- fur-2-yl) acetamido] ceph-3-em-4-carboxylate.
- Biaxin (clarithromycin) is commercially available from Abbott and is 6- O-methylerythromycin.
- Dynabac (dirithromycin) is commercially available from Sanofi and is (9S)-9-Deox-l l-deoxy-9, 1 l-[imino [(7i?)-2-(2-methoxyethoxy)-ethylidene] oxy] erythromycin.
- E.E.S. 200 (Erythromycin Ethylsuccinate) is commercially available from Abbott and is erythromycin 2'-(ethylsuccinate).
- E.E.S. 400 (Erythromycin Ethylsuccinate) is commercially available from Abbott and is erythromycin 2'-(ethylsuccinate).
- Ery-Ped 200 (Erythromycin Ethylsuccinate) is commercially available from Abbott and is erythromycin 2'-(ethylsuccinate).
- EryPed 400 (Erythromycin Ethylsuccinate) is commercially available from Abbott and is erythromycin 2'-(ethylsuccinate).
- Ery-Tab (Erythromycin delayed-release tablets) is commercially available from Abbott and is (3R*. 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-Q!-L- ⁇ o-hexopyranosyl) oxy]- 14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy- 3-(dimethylamino)-
- Erythrocin Stearate (Erythromycin stearate) is commercially available from Abbott and is the stearate salt of (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl- ⁇ -L- ⁇ 6o- hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3-(dimethylamino)-
- Ilosone (erythromycin estolate) is commercially available from Dista and is erythromycin 2'-propionate, dodecyl sulfate.
- PCE Dispertab (erythromycin particles in tablets) is commercially available from Abbott and is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-0-methyl- ⁇ -L- ⁇ 6o-hexopyranosyl) oxy]- 14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy- 3-(dimethylamino)-/3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
- Pediazole erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension
- erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension is commercially available from Ross Products and is T- ethylsuccinyl ester of erythromycin (erythromycin ethylsuccinate) and N-(3, 4- dimethyl-5-isoxazolyl)-N-sulfanilylacetamide (sulfisoxazole acetyl).
- Tao (troleandomycin) is commercially available from Pfizer and is the synthetically derived acetylated ester of oleandomycin.
- Zithromax (azithromycin) is commercially available from Pfizer and is
- Pharmacia & Upjohn is the hydrated hydrochloride salt of clindamycin, a semisynthetic antibiotic produced by a 7 (S)-chlorosubstitution of the (7R) hydroxyl group of lincomycin.
- Cleocin Phosphate (clindamycin phosphate) is commercially available from Pharmacia & Upjohn and is L-tAre ⁇ - ⁇ -D-g ⁇ / ⁇ cto-Octopyranoside, methyl 7 chloro-6, 7, 8,-trideoxy-6-[[(l-methyl-4-propyl-2-pyrrolidinyl) carbonyl] amino]-l-thio-, 2-(dihydrogen phosphate), (2S-tran$)-.
- Coly-Mycin M (colistimethate sodium) is commercially available from Monarch.
- Vancocin HCl vancomycin hydrochloride is commercially available from Lilly.
- Amoxil (amoxicillin) is commercially available from SmithKline Beecham and is (2S, 5R, 6i?)-6-[(i-)-(-)-2-amino-2-(p-hydroxyphenyl) acetamido]-3, 3-dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0]-heptane-2- carboxylic acid trihydrate.
- Augmentin (amoxicillin/clavulanate potassium) is commercially available from SmithKline Beecham and is (2S, 5R, 6i?)-6-[(i?)-(-)-2-amino-2-(p- hydroxy phenyl) acetamido]-3, 3-dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0]- heptane-2-carboxylic acid trihydrate (amoxicillin) and potassium (Z)-(2R, 5R)-3- (2-hydroxyethylidene)-7-oxo-4-oxa-l-azabicyclo [3.2.0]-heptane-2-carboxylate (clavulanate potassium).
- Bicillin C-R 900/300 (Penicillin G benzathine and Penicillin G procaine suspension) is commercially available from Wyeth-Ayerst and is (IS, 5R, 6R)-3, 3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heptane-2- carboxylic acid compound with N, N'-dibenzylethylenediamine (2:1), tetrahydrate (Penicillin G benzathine) and (25, 5R, 6R)-3, 3-Dimethyl-7-oxo-6- (2-phenylacetamido)-4-thia-l-azabicyclo [3.2.0] he ⁇ tane-2-carboxylic acid compound with 2-(diethylamino) ethyl />-amino benzoate compound (1:1) monohydrate (Penicillin G procaine) .
- Bicillin C-R (Penicillin G benzathine and Penicillin G procaine suspension) is commercially available from Wyeth-Ayerst and is (2S, 5R, 6R)-3, 3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heptane-2- carboxylic acid compound with N, N'-dibenzylethylenediamine (2:1), tetrahydrate (Penicillin G benzathine) and (2S, 5R, 6R)-3, 3-Dimethyl-7-oxo-6- (2-phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylic acid compound with 2-(diethylamino) ethyl />-amino benzoate compound (1:1) monohydrate (Penicillin G procaine).
- Bicillin L-A (Penicillin G benzathine suspension) is commercially available from Wyeth-Ayerst and is (25, 5R, 6R)-3, 3-Dimethyl-7-oxo-6-(2- phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylic acid compound with N, N'-dibenzylethylenediamine (2:1), tetrahydrate.
- Geocillin (carbencillin indanyl sodium) is commercially available from Pfizer and is l-(5-Indanyl)-N-(2-carboxy-3-3-dimethyl-7-oxo-4-thia-l- azabicyclo [3.2.0] hept-6-yl)-2-phenylmalonamate monsodium salt.
- Mezlin sterile mezlocillin sodium
- Bayer is the monohydrate sodium salt of 6- ⁇ D-2[3[(methyl-sulfonyl)-2-oxo- imidazolidine-l-carboxamido]-2-phenyl acetamido ⁇ penicillanic acid.
- Omnipen (ampicillin) is commercially available from Wyeth-Ayerst and is (2S, 5R, 6R)-6-[(R)-2-Amino-2-phenylacetamido]-3, 3-dimethyl-7-oxo-4-thia- 1-aza-bicyclo [3.2.0] heptane-2-carboxylic acid.
- Pen-Vee K (penicillin V potassium) is commercially available from Wyeth-Ayerst and is the potassium salt of the phenoxymethyl analog of penicillin G.
- Pfizerpen (penicillin G potassium) is commercially available from Pfizer and is monopotassium 3, 3-dimethyl-7-oxo-6-(2-phenylacetarnido)-4-thia-l- azabicyclo (3.2.0) heptane-2-carboxylate.
- Pipracil (piperacillin sodium) is commercially available from Lederle and is 4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylic acid, 6-[[[[(4-ethyl-2-3- dioxo-1-piperazinyl) carbonyl] amino] phenylacetyl] amino] -3, 3-dimethyl-7- oxo-, monosodium salt, [2S-[2 ⁇ , 5a, 6 ⁇ (S*)]].
- Spectrobid (bacampicillin HCl) is commercially available from Pfizer and is r-ethoxycarbonyloxyethyl-6-(D-C ⁇ aminophenylacetamide)-penicillate hydrochloride.
- Ticar (ticarcillin disodium) is commercially available from SmithKline Beecham and is N-(2-carboxy-3, 3-dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0] hept-6-yl)-3-thiophenemalonamic acid disodium salt.
- Timentin (ticarcillin disodium and clavulanate potassium) is commercially available from SmithKline Beecham and is N-(2-carboxy-3, 3- dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0] hept-6-yl)-3-thiophenemalonamic acid disodium salt (ticarcillin disodium) and potassium (Z)-(2R, 5R)-3-(2- hydroxyethylidene)-7-oxo-4-oxa-l-azabicyclo [3.2.0] heptane-2-carboxylate (clavulanate potassium).
- Unasyn is commercially available from Pfizer and is monosodium (2S, 5R, 6R)-6-[(R)-2-Amino-2-phenyl acetamido]-3, 3-dimethyl-7-oxo-4-thia-l-aza-bicyclo [3.2.0] heptane-2- carboxylate (amipicillin sodium), and sodium penicillate sulfone; sodium (2S, 5R)-3, 3-dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylate 4, 4- dioxide (sulbactam sodium).
- Zosyn (piperacillin sodium and tazobactam sodium) is commercially available from Lederle and is sodium (2S, 5R, 6i?)-6[(i?)-2-(4-ethyl-2, 3-dioxo-l- piperazine-carboxamido)-2-phenylacetamido] -3, 3 -dimethyl-7-oxo-4-Thia- 1 - azabicylco-[3.2.0] heptane-2-carboxylate (piperacillin sodium), and sodium (2S, 3S, 5R) -3-methyl-7-oxo-3-(l#-l, 2, 3-triazol-l-ylmethyl)-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylate-4, 4-dioxide (tazobactam sodium).
- Dicloxacillin Sodium is monosodium (2S,5R,6R)-6-(3-(2,6- dichloro ⁇ henyl)5-methyl-4 -isoxazolecarboxamido]-3,3-dimethyl-7-OXO-4- thia-l-azabicyclo[3.2.0] heptane-2-carboxylate monohydrate.
- Achromycin V (tetracycline HCl) is commercially available from Lederle and is the monohydrochloride of [4S-(4 ⁇ , 4a ⁇ , 5a ⁇ ; 6/3, 12a ⁇ ,)]-4- (Dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 6, 10, 12, 12a- pentahydroxy-6- methyl- 1, ll-dioxo-2-naphthacenecarboxamide.
- Declomycin (demeclocycline HCl) is commercially available from
- Dynacin (minocylcine HCl) is commercially available from Medicis and is [4S-(4 ⁇ , 4a ⁇ , 5a ⁇ , 12a ⁇ )]-4, 7-bis (dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a- octahydro-3, 10, 12, 12a-tetrahydroxy-l, ll-dioxo-2-napthacene carboxamide monochloride.
- Minocin (minocycline hydrochloride) is commercially available from Lederle Laboratories and is [4S-(4 ⁇ , 4a ⁇ , 5a ⁇ , 12a ⁇ )]-4, 7-bis (dimethylamino)- 1, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 10, 12, 12a-tetrahydroxy-l, ll-dioxo-2- napthacene carboxamide monochloride.
- Monodox (Doxycycline monohydrate capsules) is commercially available from Oclassen and is ⁇ -6-deoxy-5-oxytetracycline.
- Vibramycin Calcium (doxycycline sodium) is commercially available from Pfizer and is 4-(Dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 5, 10, 12, 12a-pentahydroxy-6-methyl-l, ll-dioxo-2-napthacene-carboxamide monohydrate.
- Vibramycin Hyclate (doxycycline hyclate) is commercially available from Pfizer and is c.-6-deoxy-5-oxytetracycrine.
- Vibramycin Monohydrate (doxycycline monohydrate) is commercially available from Pfizer and is 4-(Dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a- octahydro-3, 5, 10, 12, 12a-pentahydroxy-6-methyl-l, ll-dioxo-2-napthacene- carboxamide monohydrate.
- Vibra-Tabs (doxycycline hydrate) is commercially available from Pfizer and is ⁇ - ⁇ -deoxy-S-oxytetracycline.
- Vibramycin (doxycycline) is commercially available from Pfizer and is 4-(Dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 5, 10, 12, 12a- ⁇ entahydroxy-6-methyl- 1, 11 -dioxo-2-napthacene-carboxamide monohydrate.
- Lincomycins is monosodium (2S,5R,6R)-6-(3-(2,6-dichlorophenyl)5- methyl-4 -isoxazolecarboxamido]-3,3-dimethyl-7-OXO-4-thia-l- azabicyclo[3.2.0] heptane-2-carboxylate monohydrate.
- Cleocin HCl (clindamycin HCl) is commercially available from Pharmacia & Upjohn and is Methyl 7-chloro-6, 7, 8-trideoxy-6-(l-methyl-tr ⁇ «s- 4-propyl-L-2-pyrrolidine carboxamido)- 1 -thio-L-threo-a-D-galacto- octopyranoside monohydrochloride.
- Abelcet (amphotericin B lipid complex) is commercially available from Libosome Company, Inc. and is [IR-(IR*, 3S*, 5R*, 6R*, 9R* 5 HR*, 15S*, 16R*, 17R*, 18S*, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R*, 35S*, 36R*, 37S*)]-33-[(3-amino-3, 6-dideoxy-j3-D-mannopyranosyl)-oxy]-l, 3, 5, 6, 9, 11, 17, 37-octahydroxy-15, 16, 18-trimethyl-13-oxo-14, 39-dioxabicyclo [33.3.1] nonatriaconta-19, 21, 23, 25, 27, 29, 31-heptaene-36-carboxylic acid.
- AmBisome (amphotericin B) is commercially available from Fujisawa Healthcare and is [IR-(IR*, 3S*, 5R*, 6R* 5 9R*, 1 IR*, 15S*, 16R*, 17R*, 18S*, 19E, 21E, 23E, 25E, 27E, 29E, 3 IE, 33R*, 35S*, 36R*, 37S*)]-33-[(3- amino-3, 6-dideoxy-
- Amphotec (amphotericin B cholesterol sulfate complex) is commercially available from Sequus Pharmaceuticals, Inc. and is [IR-(IR*, 3S*, 5R*, 6R*, 9R*, HR*, 15S*, 16R*, 17R*, 18S*.
- flucytosine is commercially available from ICN Pharmaceuticals and is 5-fluorocytosine.
- Diflucan (fluconazole) is commercially available from Pfizer Inc. and is 2, 4-difluoro-Q!- ol-bis (IH-I, 2, 4-triazol-l-ylmethyl) benzyl alcohol.
- Fulvicin P/G (ultramicrosize griseofulvin) is commercially available from Schering.
- Fulvicin P/G 165 and 330 (ultramicrosize griseofulvin) is commercially available from Schering.
- Grifulvin V (griseofulvin) is commercially available from Ortho
- Gris-PEG (griseofulvin ultramicrosize) is commercially available from Allergan.
- Lamisil (terbinafme hydrochloride) is commercially available from Novartis and is (E)-N-(6, 6-dimethyl-2-hepten-4-ynyl)-N-methyl- 1 - naphthalenemethanamine hydrochloride.
- Nizoral (ketoconazole) is commercially available from Janssen and is cis l-acetyl-4-[4-[[2-(2, 4-di-chlorophenyl)-2-(lH-imidazol-l-yhnethyl)-l, 3- dioxolan-4-yl] methoxy] phenyl] piperazine.
- Amphotericin B is [IR-(IR*, 3S*, 5R*, 6R*, 9R*, 1 IR*, 15S*, 16R*,
- Dapsone tablets (dapsone) is commercially available from Jacobus and is 4, 4'-diaminodiphenyl-sulfone (DDS).
- DDS 4, 4'-diaminodiphenyl-sulfone
- Diflucan (fluconazole) is commercially available from Pfizer and is 2, 4- difluoro- ⁇ - ⁇ '-bis (IH-1, 2, 4-triazol-l-ylmethyl) benzyl alcohol.
- Monistat-Derm cream (miconazole) is commercially available from Ortho Dermatological and is l-[2, 4-dichloro-/3- ⁇ (2, 4-dichlorobenzyl) oxy ⁇ phenethyl] imidazole mononitrate.
- Mycostatin Cream (nystatin) is commercially available from Westwood- Squibb.
- Sporanox is commercially available from Janssen Pharmaceutical and is ( ⁇ )-l-[(R*)-sec-bvAyl]-4- ⁇ p-[[2R*, 45 r *)-2-(2, 4- dichlorophenyl)-2-(lH-l, 2, 4-triazol-l-ylmethyl)-l, 3-dioxolan-4-yl] methoxy] phenyl] -1-piperazinyl] phenyl]- ⁇ 2 -l, 2, 4, triazolin-5-one mixture with ( ⁇ )-l- [(R*ysec-but ⁇ l]-4- ⁇ p-[[2R*, 45*)-2-(2, 4-dichlorophenyl)-2-(lH-l, 2, 4-triazol- l-ylmethyl)-l, 3-dioxolan-4-yl] methoxy] phenyl] -1-piperazinyl] ⁇ henyl]- ⁇ 2 -l
- Aralen hydrochloride (chloroquine HCl) is commercially available from Sanofi Pharmaceuticals and is 7-(chloro-4-[[4-diethylamino)-l-methyl butyl] amino] -quinoline dihydrochloride.
- Aralen phosphate (chloroquine phosphate) is commercially available from Sanofi Pharmaceuticals and is 7-(chloro-4-[[4-diethylamino)-l-methyl butyl] amino] -quinoline phosphate (1:2).
- Daraprim (pyrimethamine) is commercially available from Glaxo Wellcome and is 5-(4-chlorophenyl)-6-ethyl-2, 4-pyrimidinediamine.
- Lariam (mefloquine HCl) is commercially available from Roche Laboratories and is (R*, S*)-( ⁇ )-ce-2-piperidinyl-2, 8-bis (trifluoromethyl)-4- quinoline methanol hydrochloride.
- Plaquenil hydroxychloroquine sulfate
- Capastat sulfate is commercially available from
- Myambutol (ethambutol hydrochloride) is commercially available from Lederle Laboratories.
- Mycobutin (rifabutin capsules) is commercially available from Pharmacia & Upjohn and is 1', 4-didehydro-l-deoxy-l, 4-dihydro-5'-(2- methylpropyl)-l-oxorifamycin XIV or (95, 12E 5 US, ⁇ 5R, 16S, HR, 18 ⁇ , 19R, 2OS, 21S, 22E, 24Z)-6, 16, 18, 20-tetrahydroxy-l-l'-isobutyl-14-methoxy-7, 9, 15, 17, 19, 21, 25-heptamethyl-spiro [9, 4-(epoxypentadeca [1, 11, 13] trienimino)-2H-furo [T, 3':7, 8] naphth [1, 2-d] imidazole-2, 4'-pi ⁇ eridine]-5, 10, 26-(3H, 9H)-trione-16-acetate.
- Nydrazid isoniazid injection
- Nydrazid injection is commercially available from Apothecon.
- Paser is commercially available from Jacobus and is 4-amino-2-hydroxy benzoic acid.
- Priftin rifapentine
- Priftin rifapentine
- rifapentine is commercially available from Hoechst Marion Roussel and is rifamycin 3-[[(4-cyclo-pentyl-l-piperazinyl) imino] methyl] or 3[N-(4-cyclopentyl-l-piperazinyl)-formimyid.oyl]-2,7-(epoxypentadeca [1, 11, 13] trienirnino)naptho [2,1-b] furan-1, 11 (2H)-dione 21 -acetate.
- Pyrazinamide tablets pyrazinamide
- Rifadin rifampin capsules
- Rifadin is commercially available from Hoechst Marion Roussel and is 3-[[(4-methyl-l-piperazinyl) imino] methyl] rifamycin or 5, 6, 9, 17, 19, 21-hexahydroxy-23-methoxy-2, 4, 12, 16, 20, 22-heptamethyl-8- [N-methyl-1-piperazinyl) formimidoyl]-2,7-(epoxy pentadeca [1,11,13] trienimino)naptho [2,1-b] furan-1, 11 (2H)-dione 21 -acetate.
- Rifadin IV (rifampin for injection) is commercially available from Hoechst Marion Roussel and is 3-[[3-(4-methyl-l-piperazinyl) formimidoyl]- 2,7-(epoxy pentadeca [1, 11, 13] trienimino) naphtho [2, 1-b] furan-1, 11 (2H)- dione 21 -acetate.
- Rifamate (rifampin and isoniazid) is commerically available from Hoechst Marion Roussel and is 3-(4-methyl-l-piperazinyliminomethyl) rifamycin SV (rifampin) and hydrazide of isonicotinic acid (isoniazid).
- Rifater (rifampin, isoniazid and pyrazinamide) is commercially available from Hoechst Marion Roussel and is 3-(4-methyl- 1 -piperazinyliminomethyl) rifamycin SV (rifampin), hydrazide of isonicotinic acid (isoniazid), and pyrazine analogue of nicotinamide (pyrazinamide).
- Seromycin (cycloserine capsules) is commercially available from Dura Pharmaceuticals and is 3-isoxazolidinone, 4-amino-, (R)-.
- Streptomycin Sulfate is commercially available from Pfizer and is O-2- deoxy-2-(methylamino)-o;-L-glyucopyransoyl-(l->2)-0-5-deoxy-3-C-formyl- ⁇ - L-lyxofuranosyl-(l ⁇ 4)-N-N'-bis(aminoiminomethyl)-, sulfate (2:3) salt.
- Tice BCG (BCG vaccine) is commercially available from Organon and is attenuated live Mycobacterium bovis strains Bacillus of Calmette and Guerin. Cycloserine (seromycin capsules) is commercially available from Dura
- Nydrazid (Isoniazid) is commercially available from Apothecon and is the hydrazide of isonicotinic acid.
- Urised is commercially available from Poly Medica.
- Trecator-SC ethionamide tablets
- Wyeth-Ayerst is commercially available from Wyeth-Ayerst and is 2-ethylthioisonicotinamide.
- Alferon N (interferon alfa-n3) is commercially available from Interferon Sciences and is interferon alfa-n3 (human leukocyte derived).
- Crixivan (indinavir sulfate) is commercially available from Merck & Co.,
- Cytovene (ganciclovir) is commercially available from Roche and is 9- [[2-hydroxy-l (hydroxymethyl) ethoxy] methyl] guanine.
- Cytovene-IV (ganciclovir sodium) is commercially available from Roche and is 9- [[2-hydroxy-l (hydroxymethyl) ethoxy] methyl] guanine.
- Epivir (lamivudine) is commercially available from Glaxo Wellcome and is (2R 5 cis)-4-amino-l-(2-hydroxymethyl-l, 3-oxathiolan-5-yl)-lH)-pyrimidin-2- one.
- Famvir (famciclovir) is commercially available from SmithKline Beecham and is 2-[2-(2-amino-9H-purin-9-yl) ethyl]-l, 3-propanediol diacetate.
- Flumadine (rimantadine HCl) is commercially available from Forest and is alpha-methyltricyclo-[3.3.1.1/3.7] decane-1-methanamine hydrochloride.
- Foscavir (foscarnet sodium) is commercially available from Astra and is phosphonoformic acid, trisodium salt.
- Hivid (zalcitabine) is commercially available from Roche and is 4- amino-l-beta-D-2 1 , 3', dideoxyribofuranosyl-2-(lH)-pyrimidone or 2',3'- dideoxycytidine.
- hitron A (interferon alfa-2b) is commercially available from Schering.
- Invirase quinavir mesylate
- Roche Labs N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2- quinolylcarbonyl)-L-asparaginyl] amino] butyl-(4aS, 8aS)-isoquinoline-3(S)- carboxamide methanesulfonate.
- Norvir (ritonavir) is commercially available from Abbott and is 10-
- Rebetron combination therapy which contains Rebetrol (ribavirin which is 1- ⁇ -D-ribofuranosyl-lH-l, 2, 4-triazole-3-carboxamide) and Intron A (inteferon alfa-2b), is commercially available from Schering.
- Rescriptor (delavirdine mesylate) is commercially available from Pharmacia & Upjohn and is pieperazine, l-[3-[(l-methylethyl) amino]-2- pyridinyl]-4-[[5(methylsulfonyl)-amino]-lH-indol-2-yl] carbonyl], monomethanesulfonate.
- Retrovir (ziduvudine) is commerically available from Glaxo Wellcome and is 3'-azido-3'-deoxythymidine. Retrovir IV (zidovudine) is commercially available from Glaxo-
- Symmetrel (amantadine hydrochloride) is commercially available from Endo Pharmaceuticals and is 1-adamantanamine hydrochloride.
- Synagis (palivizumab) is commercially available from Medlmmune Inc. and is humanized monoclonal antibody (IgGl ⁇ ).
- Valtrex (valacyclovir HCl) is commercially available from Glaxo Wellcome and is L-valine, 2-[(2-amino-l,6-dihydro-6-oxo-9H-purin-9-yl) methoxy] ethyl ester, monohydrochloride.
- Videx (didanosine) is commercially available from Bristol-Myers Squibb Oncology/Immunology and is 2',3'-di-deoxyinosine.
- Viracept (nelfinavir mesylate) is commercially available from Agouron and is [3S-[2(2S*, 3S*), 3a, 4aft 8a/3]]-N-(l,l-dimethylethyl)decahydro-2-[2- hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-(phenylthio)butyl]-3- isoquinolinecarboxcamide mono-methanesulfonate (salt).
- Viramune (nevirapine) is commercially available from Roxane and is 11- cyclopropyl-5,1 l-dihydro-4-methyl-6H-dipyrido [3,2-b:2',3'-][l,4] diazepin-6- one.
- Virazole (ribavirin) is commercially available from ICN and is 1-beta-D- riboruranosyl- IH-1 ,2,4-triazole-3 -carboxamide. Vistide (cidofovir) is commercially available from Gilead Sciences and is l-[(5)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate (HPMPC).
- Zerit stavudine (d4T)
- d4T Strevudine
- Symmetrel Syrup amantadine HCl
- Endo Labs is 1-adamantanamine hydrochloride.
- Combivir Tablets (lamiduvine) is commercially available from Glaxo Wellcome and is 2',3'-didehydro-3'-deoxythymidine.
- Zovirax (acyclovir) is commercially available from Glaxo Wellcome and is 2-amino-l ,9-dehydro-9-[(2-hydroxyethyoxy)methyl]-6H-purin-6-one.
- Dapsone Tablets (dapsone) is commercially available from Jacobus and is 4,4'-diaminodiphenylsulfone (DDS).
- DDS 4,4'-diaminodiphenylsulfone
- Daraprim (pyrimethamine) is commercially available from Glaxo Wellcome and is 5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine.
- Flagyl 375 (metronidazole) is commercially available from Searle and is 2-Methyl-5-nitro-imidazole-l-ethanol.
- Flagyl ER Tablets (metronidazole) is commercially available from Searle and is 2-Methyl-5-nitro-imidazole-l-ethanol.
- Flagyl LV. (metronidazole) is commercially available from SCS and is 2-
- Furoxone (furazolidone) is commercially available from Roberts and is 3-(5-nitrofurfuryliden-amino)-2-oxazolidinone.
- Mepron (atovaquone) is commercially available from Glaxo Wellcome and is tr ⁇ «5-2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-l,4-naphthalenedione.
- Neutrexin (trimetrexate glucuronate) is commercially available from U.S. Bioscience and is 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline mono-D-glucuronate.
- Cipro (ciprofloxacin HCl) is commercially available from Bayer and is the monohydrochloride monohydrate salt of 1 -cyclopropyl- ⁇ -fluoro- 1 , 4- dihydro-4-oxo-7-(l -piperazinyl)-3-quinolinecarboxylic acid.
- Floxin (ofloxacin) is commercially available from Ortho-McNeil Pharmaceutical and is ( ⁇ )-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-l- piperazmyl)-7-oxo-7H-pyrido[l,3,3-de]-l,4-benzoxazine-6-carboxylic acid.
- Levaquin (levofloxacin) is commercially available from Ortho-McNeil
- Noroxin (norfloxacin) is commercially available from Merck and is 1- ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)-3-quinolinecarboxylic acid.
- Penetrex (enoxacin) is commercially available from Rh ⁇ ne-Poulenc Rorer and is l-ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)-l,8- naphthyridine-3-carboxylic acid sesquihydrate.
- Raxar (grepafloxacin HCl) is commercially available from Glaxo Wellcome and is ( ⁇ )-l-cyclopropyl-6-fluoro-l,4-dihydro-5-methyl-7-(3-methyl- l-piperazinyl)-4-oxo-3-quinolinecarboxylic acid monochloride sesquihydrate.
- Trovan trovafloxacin mesylate
- Pfizer is (I D, 5D, 6a)-7-(6-amino-3-azabicyclo[3.1.0]hex-3-yl)-l-(2,4- difluoro ⁇ henyl)-6-fluoro-l,4-dihydro-4-oxo-l,8-naphtliyridme-3-carboxylic acid, monomethanesulfonate.
- Zagam (sparfloxacin) is commercially available from Rh ⁇ ne-Poulenc Rorer and is 5-Amino-l-cyclopropyl-7-m-3,5-dimethyl-l-piperazinyl)-6,8- difluoro-1,4, dihydro-4-oxo-3-quinolinecarboxylic acid.
- Bactrim (trimethoprim and sulfamethoxazole) is commercially available from Roche Labs and is 2,4-diamino-5-(3,4,5-trimethoxybenzyl) pyrimidine (trimethoprim) and N 1 ,- (5-methyl-3-isoxazolyl)sulfanilamide (sulfamethoxazole) .
- Bactrim DS (trimethoprim and sulfamethoxazole double strength) is commercially available from Roche Labs and is 2,4-diamino-5-(3,4,5- trimethoxybenzyl) pyrimidine (trimethoprim) and N 1 ,- (5-methyl-3- isoxazolyl)sulfanilamide (sulfamethoxazole).
- Pediazole erythromicin ethylsuccinate and sulfisaxazole acetyl
- erythromicin ethylsuccinate and sulfisaxazole acetyl is commercially available from Ross and is erythromicin 2'-(ethyl succinate) and N' acetyl sulfisoxazole (sulfisoxizole is N-(3,4-Dimethyl-5-isoxazolyl)-N-sulfanilyl acetamide.
- Septra (trimethoprim and sulfamethoxazole) is commercially available from Monarch and is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4- pyrimidinediarnine (trimethoprim) and 4-amino-N-(5-methyl-3- isoxazolyl)benzenesulfonamide (sulfamethoxazole).
- Septra DS (trimethoprim and sulfamethoxazole) is commercially available from Monarch and is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4- pyrimidinediamine (trimethoprim) and 4-amino-N-(5-methyl-3- isoxazolyl)benzenesulfonamide (sulfamethoxazole) .
- Co-trimoxazole is a combined chemotherapeutic agent consisting of trimethoprim (T) and the sulphonamide sulphamethoxazole (S); their ratio is 1:5.
- co-trimoxazole It is bactericidal by virtue of a sequential blockade of the folic acid synthesis in micoorganisms.
- the antimicrobial spectrum of co-trimoxazole includes many Gram-positive and Gram-negative aerobes, Chlamydias, nocardias, protozoas (Pneumocystis carinii), etc.
- co- trimoxazole mainly has practical importance against Gram-positive aerobes (urinary tract infections), pneumococci, and haemophilus influenzae (respiratory tract infections and otitis), http://www.infomed.org/100drugs/ctrifram.html.
- Bactrim LV. Infusion (sulfamethoxazole) is commercially available from Roche Labs.
- Pediazole erythromicin ethylsuccinate and sulfisoxazole acetyl
- erythromicin ethylsuccinate and sulfisoxazole acetyl is commercially available from Ross and is erythromicin 2'-(ethyl succinate) and N' acetyl sulfisoxazole (sulfisoxizole is N-(3,4-Dimethyl-5-isoxazolyl)-N-sulfanilyl acetamide.
- Furadantin nitrogenantoin
- Dura is 1-
- Macrobid (nitrofurantoin monohydrate macrocrystals) is commercially available from Procter & Gamble Pharmaceuticals and is l-[[[5-nitro-2- furanyl]methylene] amino] -2-4-imidazolidinedione monohydrate.
- Macrodantin (nitrofurantoin macrocrystals) is commercially available from Procter & Gamble Pharmaceuticals and is l-[[[5-nitro-2- furanyl]methylene] amino]-2-4-iniidazolidinedione.
- Monurol Sachet (fosfomycin tromethamine) is commercially available from Forest and is (IR, 2S)-(1, 2-epoxypropyl) phosphonic acid, compound with 2-amino-2-(hydroxymethyl)-l ,3-propanediol (1:1).
- NegGram Caplets (nalidixic acid) is commercially available from Sanofi and is 1 -ethyl- l,4-dihydro-7-methyl-4-oxo-l,8-naphthyridine-3-carboxylic acid.
- Septra (trimethoprim and sulfamethoxazole) is commercially available from Monarch and is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4- pyriniidinediamine (trimethoprim) and 4-amino-N-(5-methyl-3- isoxazolyl)benzenesulfonamide (sulfamethoxazole).
- Septra DS (trimethoprim and sulfamethoxazole) is commercially available from Monarch and is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4- pyrimidinediamine (trimethoprim) and 4-amino-N-(5-methyl-3- isoxazolyl)benzenesulfonamide (sulfamethoxazole).
- Urised a combination of the antiseptics methenamine, methylene blue, phenyl salicylate, benzoic acid and parasympatholytics (atropine sulfate) hyoscyamine
- Urobiotic-250 Capsules oxytetracycline HCl, sulfamethizole and phenazopyridine HCl
- Uroqid Acid No. 2 Tablets (methenamine mandelate) is commercially available from Beach.
- Bactroban (mupirocin) is commercially available from SmithKline Beecham and is (aE, 2S, 3R,4R,5S)-5-[(2S,3SAS,5S)-2,3-Epoxy-5-hydroxy-4- methylhexyl]tetraliydro-3 ,4-dihydroxy-j3-methyl-2H-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2:1), dihydrate.
- Chloromycetin opthalmic is commercially available from Monarch and is (1) Acetamide, 2,2-dichloro-iV-[2-hydroxy-l- (hydroxymethyl)-2-(4-nitrophenyl) ethyl]-, and (2) D-t/*re ⁇ -(-)-2,2-Dichloro-N- [ ⁇ -hydroxy- ⁇ -(hydroxymethyl)-p-nitrophenethyl] acetamide.
- Cortisporin (neomycin and polymyxin ⁇ sulfates and hydrocortisone acetate cream) is commercially available from Monarch and is 21-(acetyloxy)- 1 IB, 17-dihydroxypregn-4-ene-3 ,20-dione.
- Ilotycin (erythromycin opthalmic ointment) is commercially available from Dista and is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4- [(2, ⁇ -dideoxy-S-C-methyl-S-O-methyl- ⁇ -L-rf ⁇ o-hexopyranosyl) oxy]-14-ethyl- 7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3- (dimethylamino)-j3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
- NeoDecadron neomycin sulfate - dexamethasone sodium phosphate
- Merck is 9-fluoro-llj8, 17-dihydroxy-16ce- methyl-21-(phosphonooxy)pregna-l, 4-diene-3, 20-dione disodium salt.
- Polytrim trimethoprim and polymyxin ⁇ sulfate opthalmic solution
- trimethoprim 2,4-diamino-5-(3 ,4,5- trimethoxylbenzl)pyrimidine
- trimethoprim 2,4-diamino-5-(3 ,4,5- trimethoxylbenzl)pyrimidine
- trimethoxylbenzl polymyxin B 1 and B 2
- Terra-Cortril oxytetracycline HCl and hydrocortisone acetate
- TobraDex tobramycin and dexamethasone opthalmic suspension and ointment
- Alcon is O-3-Amino-3-deoxy-a- D-glucopyranosyl-(l ->4)-O- [2,6-diamino-2,3,6-trideoxy-a-D- ⁇ o- hexopyranosyl-l(l-»6)] -2-deoxy-L-streptamine.
- Dexamethasone Chemical Name: 9-Fluro- 1 Ib, 17,21 -trihydroxy- 16a-methylpregna- 1 ,4-diene-3,20-dione.
- Vira-A opthalmic ointment, 3% (vidarabine) is commercially available from Monarch and is 9H-Purin-6-arnine, 9- ⁇ -D-arabinofuranosyl-, monohydrate.
- Chibroxin (norfloxacin opthalmic solution) is commercially available from Merck and is l-ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)-3- quinolinecarboxylic acid.
- Ciloxan opthalmic solution (Ciprofloxacin HCl) is commercially available from Alcon and is the monohydro chloride monohydrate salt of 1- cyclopropyl-6-fluoro-l, 4-dihydro-4-oxo-7-(l-piperazinyl)-3-quinoline- carboxylic acid.
- Ciloxan opthalmic ointment (Ciprofloxacin HCl) is commercially available from Alcon and is the monohydro chloride monohydrate salt of 1- cyclopropyl-6-fluoro-l, 4-dihydro-4-oxo-7-(l-piperazinyl)-3-quinoline- carboxylic acid.
- Ocuflox opthalmic solution (ofloxacin) is commercially available from
- Blephamide opthalmic ointment (sulfacetamide sodium and prednisolone acetate) is commercially available from Allergan and is N-sulfanilyl-acetamide monosodium salt monohydrate (sulfacetamide sodium) and 11 ⁇ , 17,21 - trihydroxypreyna-1, 4-diene-3,20-dione 21-acetate (prednisolone acetate).
- Blephamide opthalmic suspension (sulfacetamide sodium and prednisolone acetate) is commercially available from Allergan and is N- sulfanilyl-acetamide monosodium salt monohydrate ( sulfacetamide sodium) and ll j ⁇ ,17,21-trihydroxypreyna-l, 4-diene-3,20-dione 21-acetate (prednisolone acetate).
- A/T/S (erythromycin) is commercially available from Hoescht Marion Roussel and is (3R*. 4S*, 5S*, 6R*, 7R*, 9R* 5 HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-0-methyl-o;-L-n&o-hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3- (dimethylamino)-j8-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
- Bactroban (mupirocin) is commercially available from SKB and is (oiE, IS, 3i?,4i?,55)-5-[(2S,35',4S,55)-2,3-Epoxy-5-hydroxy-4-methylhexyl]tetrariydro- 3,4-dihydroxy-
- Benzamycin (erythromycin-benzoyl peroxide topical gel) is commercially available from Dermik and is (3R*, 4S* 5 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-a-L-nbo- hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3-(dimethylamino)-/3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10-dione (erythromycin).
- Betadine (povidone-iodine) is commercially available from Purdue Frederick.
- Cleocin T (clindamycin phosphate topical solution) is commercially available from Pharmacia & Upjohn and is L-t&reo-I-D-g ⁇ / ⁇ cto-Octopyranoside, methyl 7-chloro-6,7,8-trideoxy-6- [[(l-methyl-4-propyl-2-pyrrolidinyl)- carbonyl] amino]-l-thio-, 2-(dihydrogen phosphate), (2S-trans)-.
- Clindets (clindamycin phosphate pledgets) is commercially available from Stiefel and is methyl 7-chloro-6,7,8-trideoxy-6-(l-methyl-trans-4-propyl-L- 2-pyrrolidinecarboxamido)- 1 -thio-L-tAreo- D -D-g ⁇ / ⁇ cto-octopyranoside 2- (dihydrogen phospate).
- Emgel erythromycin is commercially available from Glaxo Wellcome and is (3R*,4S*,5S*,6R* > 7R*,9R* ⁇ li?*,12i?*,135*,14 ⁇ *)-4-[(2,6-Dideoxy-3- C-methyl-3-O-methyl- ⁇ -L-rz ⁇ o-hexopyranosyl)oxy]-14-ethyl-7,12,13- trihydroxy-3,5,7,9, 11 , 13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethyl-amino)-/3- D-xy/o-hexopyranosyl] oxy] oxacyclotetradecane-2, 10-dione.
- Erycette erythromycin topical solution
- Mycostatin (nystatin cream) is commercially available from Westwood- Squibb.
- Theramycin Z (erythromycin topical solution) is commercially available from Medicis and is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)- 4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-o;-L- ⁇ ' &o-hexopyranosyl) oxy]-14- ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3- (dimethylamino)-/3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
- T-Stat (erythromycin) is commercially available from Westwood-Squibb and is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6- dideoxy-3-C-methyl-3-O-methyl-ce-L- ⁇ &o-hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3-
- Exelderm (sulconazole nitrate) is commercially available from Westwood-Squibb and is ( ⁇ )-l-[2,4-dichloro-
- Fungizone (amphotericin B oral suspension) is commercially available from Bristol-Myers Squibb and is [1R-(1R*,3S*,5R*,6R*,9R*,11R*, 15S*,16R*,17R*,18S*,19E,21E,23E,25E,27E,29E,31E,33R*,35S*,36R*,37S*)] -33-[(3-Amino-3,6-dideoxy-/3-D-mannopyranosyl)-oxy]-l,3,5,6,9,ll,17,37- octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo [33.3.1] nonatriaconta- 19,21 ,23,25 ,27,29,31 -heptaene-36-carboxylic acid.
- Lamisil (terbinafme hydrochloride cream) is commercially available from Novartis and is (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-l- naphthalenemethanamine hydrochloride.
- Loprox (ciclopiroxolamine) is commercially available from Hoescht Marion Roussel and is 6-cyclohexyl-l-hydroxy-4-methyl-2(lH)-pyridone, 2- amino-ethanol salt.
- Lotrimin (clotrimazole) is commercially available from Schering and is l-(O-Chloro- ⁇ , ⁇ -diphenyl benzyl)imidazole.
- Lotrisone (clotrimazole and betamethasone diproprionate) is commercially available from Schering and is l-(O-Chloro-o!,O!-diphenyl benzyl)imidazole (clotrimazole) and 9-Fluoro-l 1/3,17,21-trihroxy- 16/3- methylpregna- 1 ,4-diene-3 ,20-dione 17,21 -diproprionate (betamethasone diproprionate).
- Mentax (butenafme HCl) is commercially available from Penederm and is N-4-tert-butylbenzyl-N-methyl- 1 -naphthalenemethylamine hydrochloride.
- Monistat-Derm (miconazole nitrate) is commercially available from Ortho Dermatological and is l-[2,4-dichloro-/3- ⁇ (2,4- dichlorobenzyl)oxy) ⁇ phenethyl]imidazole mononitrate.
- Mycelex (clotrimazole) is commercially available from Alza and is [l-(o- chloro- ⁇ ,Q!-diphenylbenzyl) imidazole.
- Mycostatin (nystatin) is commercially available from Westwood-Squibb.
- Naftin (naftifine HCl) is commercially available from Allergan and is (E)-N-Cinnamyl-N-methyl-l-naphthalene-methylamine hydrochloride.
- Nizoral (ketoconazole) is commercially available from Janssen and is cis- l-acetyl-4[4-[[2-(2,4-dichorophenyl)-2-(lH-imidazol-l-ylmethyl)-l,3-dioxolan- 4-yl]methoxy]phenyl]piperazine.
- Nystop (nystatin) is commercially available from Paddock.
- Oxistat oxiconazole nitrate is commercially available from Glaxo
- Denavir penciclovir cream
- Zovirax acyclovir
- Glaxo-Wellcome 2-amino- 1 ,9-dihydro-9-(2-hydroxyethoxy)memyl-6H- ⁇ urin-6-one.
- Benzashave (benzoyl peroxide) is commercially available from Medicis.
- Betadine (povidone-iodine) is commercially available from Purdue Frederick.
- Betasept (chlorhexidine gluconate) is commercially available from Purdue Frederick.
- Cetaphil (soap substitute) is commercially available from Galaderma.
- Clorpactin WCS-90 sodium oxychlorosene is commercially available from Guardiam Laboratories.
- Dapsone Tablets (dapsone) is commercially available from Jacobus and is 4,4'-diaminodiphenyl sulfone (DDS).
- Desquam-E (benzoyl peroxide) is commercially available from Westwood-Squibb.
- Desquam-X (benzoyl peroxide) is commercially available from Westwood-Squibb.
- Hibiclens (chlorhexidine gluconate) is commercially available from Zeneca.
- Hibistat chlorhexidine gluconate
- hnpregon tetrachlorosalicylanilide 2%) is commercially available from Fleming.
- MetroCream (metronidazole) is commercially available from Galaderma and is 2-methyl-5-nitro-lH-imidazole-l-ethanol.
- MetroGel (metronidazole) is commercially available from Galaderma and is 2-methyl-5-nitro-lH-imidazole-l-ethanol.
- Sulfacet-R sodium sulfacetamide 10% and sulfur 5%
- Sulfamylon (matenide acetate) is commercially available from Bertek and is ⁇ -amino-p-toluenesulfonamide monoacetate.
- Triaz (benzoyl peroxide) is commercially available from Medicis.
- Vanoxide-HC (benzoyl peroxide hydrocortisone) is commercially available from Dermik and is 11/3,17,2 l-trihydroxypregn-4-ene-3,20-dione (hydrocortisone) .
- Acticin permethrin is commercially available from Penederm and is
- Elimite permethrin is commercially available from Allergan and is ( ⁇ )- 3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate.
- Eurax crotamiton is commercially available from Westwood-Squibb and is N-ethyl-N-(o-methylphenyl)-2-butenamide.
- Efudex fluorouracil
- ICN is 5- flouro-2,4 (IH, 3H)-pyrimidinedione.
- Fluoroplex (fluorouracil) is commercially available from Allergan and is 5-flouro-2,4 (IH, 3H)-pyrimidinedione.
- Furadantin Oral Suspension (nitrofurantoin) is commercially available from Dura and is l-[[5-nitro-2-furanyl)methylene]amino]-2,4-imidazolidine dione.
- Zyvox (linezolid) is commercially available from Pharmacia & Upjohn.
- the antibiotic useful in the present invention is the biologically active compound present in any of the antibiotic drugs disclosed above.
- Azactam is typically available as an injectable solution.
- the antibiotic is (z)-2- [[[(2-amino-4-thiazolyl) [[(2S,-3S)-2-methyl-4-oxo-l-sulfo-3-azetidinyl] carbamoyl] methylene] amino] oxy]-2-methyl propionic acid.
- the formulation 5 can further include alpha carotene, beta carotene, vitamin A, or a combination thereof; in any suitable and effective amount.
- an adhesive patch 1 of the present invention includes a formulation 5 located on at least a portion of the front side 3 of the backing 2, in at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2.
- the formulation 5 is partially embedded in at least a portion of the front side 3 of the backing 2.
- the formulation 5 is located on a portion of the surface of front side 3 of the backing 2.
- the formulation 5 is located on the entire surface of the front side 3 of the backing 2.
- the backing 2 is defined by a front side 3 (the side exposed to the skin during use) and a back side 4 (the side exposed to the environment during use).
- the backing 2 should be nonirritating to human skin.
- the backing 2 is a self- supporting sheet of water soluble or water insoluble, polymeric or natural material that provides strength and integrity for the formulation 5.
- the backing 2 of the adhesive patch 1 can be vapor permeable.
- the backing 2 can also be porous, since porosity provides openings for receiving the formulation 5 and it helps to assure that the adhesive skin patch 1 is vapor permeable.
- the backing 2 can retain the formulation 5 while allowing moisture from the skin to pass.
- the backing 2 of the adhesive patch 1 can be vapor impermeable.
- the backing 2 can also be non-porous, which would increase the amount of skin absorption of the xanthophylls 15. Specifically, the backing 2 can retain the formulation 5 while not allowing moisture from the skin to pass.
- the backing 2 can have any suitable thickness, provided the suitable thickness allows for a flexible, bendable, pliable, and/or a stretchable sheet of water insoluble material. Specifically, the thickness of the backing 2 can be about 0.001 mm to about 5.0 mm, about 0.001 mm to about 3.0 mm, or about 0.025 mm to about 1.25 mm.
- the backing 2 can be manufactured from any suitable material, provided the suitable material can form a flexible, bendable, pliable, and/or stretchable backing 2.
- the backing 2 includes a flexible sheet of water soluble or water insoluble material that provides support for the adhesive skin patch 1.
- the backing 2 can include water soluble or water insoluble polymeric fibers, a porous film, or any other kind of matrix with spaces within the matrix.
- a specific backing 2 is a lightweight, porous, pliable strip composed of a nonwoven fabric of polymeric or natural fibers such as polyester, cotton or cellulose fibers bonded together with a sizing resin.
- the backing 2 can be woven or nonwoven.
- the backing 2 includes nonwoven fabric.
- the backing 2 can include polyester fibers, polyurethane fibers, polyolefm fibers, polyamide fibers, natural fibers, cotton fibers, copolyester fibers, cellulose acetate fibers, polycellulose fibers, or any mixture thereof. Additional stable, water insoluble flexible sheet materials and methods for manufacturing the suitable backings 2 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein, and are suitable as backings 2 according to the present invention.
- the infusion of the formulation 5 into the backing 2 can be accomplished, e.g., with the use of a continuous process mixer, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein; or as discussed herein.
- the backing 2 can be a non-woven backing 2 that is treated by coating: the front side 3 of the backing adhesive patch 1, the back side 4 of the backing 2, or both the front side 3 and back side 4 of the backing 2; with a silicone-containing compound, a fluorocarbon solution, or a combination thereof.
- Suitable silicone-containing compounds include, e.g., polydimethyl siloxanes, dialkylsiloxanes, dimethylsiloxo vinyl alkenes, dialkylsiloxo vinyl alkenes, dimethylsiloxo acrylates, dialkylsiloxo acrylates, vinyl terminated polydimethylsiloxane, and vinyl terminated polydialkylsiloxane.
- the exemplary silicone-containing compounds are commercially available from, e.g., Goldschmidt Chemical Corp. (Essen, Germany); GE Silicones (Waterford, NY); Wacker Silicone Corp. (Adrian, MI); and Dow Corning Corp. (Midland, MI).
- the backing 2 can be manufactured from a suitable non-woven fabric that is commercially available from, e.g., Freudenberg Faservliesstoffe KG (Weinham, Germany); Sontara Technologies (division of DuPont Corporation) (Old Hickory, TN); Lystil S. A. (Brignoud Cedex, France); Dexter Nonwovens (Windsor Locks, CT); and Chicopee (New Brusnwick, NJ).
- a backing material that has been treated with a sizing agent allows for the effective control of the rate of penetration, such that the gel or ointment has solidified after it has begun to penetrate the backing, but before it has passed completely through the backing, hi addition, the use of a backing material that has been treated with a sizing agent allows for the effective control of the depth to which the ointment or gel will easily penetrate before solidifying. It has surprisingly been discovered that increasing the control of the rate at which the ointment or gel penetrates the backing typically improves the overall yield of the production process by reducing the amount of material which must be discarded because the back side of the backing has become too tacky for either processing or for consumer acceptance.
- At least a portion of the backing 2 can be treated with a sizing agent 8 such that the portion of the backing 2 that is treated with the sizing agent 8 has a surface energy of about 20 dynes/cm 2 to about 65 dynes/cm 2 .
- the portion of the backing 2 that is treated with the sizing agent 8 can have a surface energy of about 27 dynes/cm 2 to about 56 dynes/cm 2 .
- the sizing agent 8 lowers the surface energy of the portion of the backing 2 that is treated with the sizing agent 8.
- Any suitable sizing agent 8 can be employed, provided the portion of the backing 2 that is treated with the sizing agent 8 has a surface energy of about 20 dynes/cm 2 to about 65 dynes/cm 2 .
- Suitable sizing agents 8 include, e.g., fluorocarbon solutions, silicone-containing compounds, and combinations thereof.
- the backing 2 can be a non-woven backing 2 that is treated with a fluorocarbon.
- the fluorocarbon treated backing 2 can be, e.g., Vilmed M1585 W/HY, Vilmed M1585H/HY, Vilmed M1586 WfHY, Vilmed M1586 H/HY, Vilmed M1570, Vilmed M1573 F, Vilmed M1573 FH, Vilmed Ml 577 F, Vilmed Ml 578 F, or Vilmed Ml 578 FH; which are all commercially available from Freudenberg Faservliesstoffe KG (Weinham, Germany).
- the silicone treated backing 2 can be a non-woven backing 2 that is coated with one or more silicone-containing compounds, e.g., a polydimethyl siloxane, a dialkylsiloxane, a dimethylsiloxo vinyl alkene, a dialkylsiloxo vinyl alkenes, a dimethylsiloxo acrylate, a dialkylsiloxo acrylate, a vinyl terminated polydimethylsiloxane, and a vinyl terminated polydialkylsiloxane.
- silicone-containing compounds e.g., a polydimethyl siloxane, a dialkylsiloxane, a dimethylsiloxo vinyl alkene, a dialkylsiloxo vinyl alkenes, a dimethylsiloxo acrylate, a dialkylsiloxo acrylate, a vinyl terminated polydimethylsiloxane, and a vinyl terminated polydialkylsiloxan
- At least a portion of the backing 2 can be treated with the sizing agent 8.
- the portion of the backing 2 that is treated with the sizing agent 8 can be that portion of the backing 2 that can typically include the formulation 5.
- the entire surface of the front side 3 of the backing 2 can be treated with the sizing agent 8 or a portion of the surface of the front side 3 of the backing 2 can be treated with the sizing agent 8.
- the entire surface of the front side 3 of the backing 2 can be treated with the sizing agent 8.
- the sizing agent 8 can penetrate at least a portion of the underlying surface (e.g., one-tenth to about nine-tenths the thickness, or about one-fourth to about nine-tenths the thickness) of the backing 2. Specifically, the sizing agent 8 can penetrate the entire underlying surface of the backing 2.
- Suitable fluorocarbon treated backings 2 include, e.g., Vilmed M1585
- the backing 2 includes a front side 3 and a back side 4.
- the adhesive skin patch 1 includes a formulation 5 located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2.
- the formulation 5 can be located on the entire surface of the front side 3 of the backing 2 or the formulation 5 can be located on a portion of the surface of the front side 3 of the backing 2.
- the formulation 5 can be located on the entire surface of the front side 3 of the backing 2. m addition to being located on the surface of the front side 3 of the backing 2, the formulation 5 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the formulation 5 can be partially embedded into the backing 2).
- the formulation 5 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein.
- the formulation 5 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2.
- the formulation 5 can be partially embedded into the backing 2.
- the formulation 5 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the formulation 5 is partially embedded into the backing 2).
- a portion of the front side 3 of the backing 2 can include the formulation 5 and other portions of the front side 3 of the backing 2 can include any combination of the pressure sensitive adhesive 14 and solvent 13.
- a central circular portion of the front side 3 of the backing 2 can include the formulation 5 while the remaining portions of the front side 3 of the backing 2 include only the pressure sensitive adhesive 14.
- the formulation 5, when partially embedded into the front side 3 of the backing 2 imparts strength and structure into the adhesive patch 1. For example, when the formulation 5 is partially embedded into the backing 2, the likelihood that the adhesive patch 1 will tear apart when separated from the release liner 10 or when removed from the skin after use, is minimized.
- the formulation 5 can be in continuous contact with the skin surface of the patient.
- the adhesive skin patch 1 upon contact with skin, will allow the skin to breathe. More preferably, the adhesive skin patch 1, upon prolonged contact with skin, will hold in place the formulation 5 and will permit the skin to breathe over prolonged periods of time typically experienced with the use of the patch, e.g., up to about 24 hours, up to about 12 hours, up to about 8 hours, or up to about 6 hours.
- the adhesive skin patch 1 can be reversibly attached to a release liner 10.
- the release liner 10 helps to maintain the adhesiveness of the adhesive skin patch 1 prior to use, such as during manufacturing, packaging, shipping, and/or storage.
- Any suitable release liner 10 can be employed for use in the present invention.
- Suitable release liners 10 are readily known to those of skill in the art. See, e.g., U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein for further descriptions of release liners 10 useful in the present invention.
- the release liner 10 can include a perforation 12 that allows the tab section 11 of the release liner 10 to be removed (see, Figs. 3, 5, and 6). Removal of the tab section 11 of the release liner 10 allows the adhesive skin patch 1 to be removed from the release liner 10 with relative ease.
- xanthophylls refers to any of several yellow accessory pigments which found in plant leaves, egg yolks and human blood plasma, these pigments are oxygenated derivatives of carotenes and are involved in photosynthesis, for example lutein, violaxanthin and neoxanthine.
- the xanthophylls 15 can be derived from alfalfa, clove, kale, spinach, squash, black bean tops, sea-weed, leafy green vegetable, or any combination thereof.
- the xanthophylls 15 can include lutein, zeaxanthin, or a combination thereof.
- xanthophylls 15 Any suitable xanthophylls 15 can be employed provided:
- the xanthophylls 15 has the desired therapeutic and/or prophylactic properties (e.g., the xanthophylls 15 effectively treats wrinkles);
- the xanthophylls 15 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the specific xanthophylls 15 will preferably be non-toxic to mammals (e.g., humans) and will be suitable for medicinal use (e.g., topically and/or via inhalation).
- the specific xanthophylls 15 will also preferably comply with any controlling or governing body of law, e.g., FDA regulations.
- lutein refers to a compound having the formula:
- Lutein is a substance of a strongly marked yellow colour, extracted from the yolk of eggs, and from the tissue of the corpus luteum. Lutein is not made in the body and must be obtained from food or vitamin supplements. Lutein is found in large amounts in green, leafy vegetables such as spinach; and legumes such as alfalfa.
- esterified form of lutein refers to a compound having the formula:
- Rl and R2 are radicals derived from fatty acids such as palmitic acid.
- zeaxanthin refers to a compound having the formula:
- Zeaxanthin is a carotene found in corn, fruits, seeds, and egg yolk.
- the xanthophylls 15 can be present in any appropriate and suitable amount, provided:
- the amount of xanthophylls 15 has the desired therapeutic and/or prophylactic properties (e.g., the xanthophylls 15 effectively kills or inactivates an airborne pathogen, respiratory tract pathogen, or a combination thereof); and
- the amount of xanthophylls 15 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the specific amount of xanthophylls 15 will preferably be non-toxic to mammals (e.g., humans) and will be suitable for medicinal use (e.g., topically and/or via inhalation).
- the specific amount of xanthophylls 15 will also preferably comply with any controlling or governing body of law, e.g., FDA regulations.
- the amount of xanthophylls 15 present in the formulation 5 will depend upon the specific compound or compounds employed as the xanthophylls 15. Specifically, the xanthophylls 15 can be present in about 0.01 wt.% to about 99.9 wt.% of the formulation 5. More specifically, the xanthophylls 15 can be present up to about 50 wt.% of the formulation 5, up to about 25 wt.% of the formulation 5, up to about 20 wt.% of the formulation 5, up to about 10 wt.% of the formulation 5, or up to about 5 wt.% of the formulation 5.
- the adhesive skin patch 1 includes an xanthophylls 15 located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2.
- the xanthophylls 15 can be located on the entire surface of the front side 3 of the backing 2 or the xanthophylls 15 can be located on a portion of the surface of the front side 3 of the backing 2.
- the xanthophylls 15 can be located on the entire surface of the front side 3 of the backing 2.
- the xanthophylls 15 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the xanthophylls 15 can be partially embedded into the backing 2). As shown in Figure 9, the xanthophylls 15 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the xanthophylls 15 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine- tenths the thickness of the backing 2. As such, the xanthophylls 15 can be partially embedded into the backing 2.
- the xanthophylls 15 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the xanthophylls 15 is partially embedded into the backing 2).
- a portion of the front side 3 of the backing 2 can include the xanthophylls 15 and other portions of the front side 3 of the backing 2 can include the pressure sensitive adhesive.
- a central circular portion of the front side 3 of the backing 2 can include the xanthophylls 15 while the remaining portions of the front side 3 of the backing 2 include only the pressure sensitive adhesive 14.
- the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human)
- the xanthophylls 15 can be in continuous contact with the skin surface of the patient.
- treating includes (i) preventing a pathologic condition (e.g., respiratory infection) from occurring (e.g. prophylaxis); (ii) inhibiting the pathologic condition (e.g., respiratory infection) or arresting its development; and (iii) relieving the pathologic condition (e.g., respiratory infection), or symptoms related to the pathologic condition.
- a pathologic condition e.g., respiratory infection
- pathologic condition e.g., respiratory infection
- mammal refers to a class of vertebrate animals of more than 15,000 species, including humans, distinguished by self-regulating body temperature, hair, and in the females, milk-producing mammae. Specifically, mammal can refer to a human.
- the solvent 13 can act as a carrier for, and preferably can dissolve, the xanthophylls 15 and/or the pressure sensitive adhesive 14. Any suitable solvent 13 can be employed, provided the solvent 13 effectively dissolves the xanthophylls 15 and/or the pressure sensitive adhesive 14 and the solvent 13 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the solvent 13 can include one or more organic compounds, one or more inorganic compounds, or mixtures thereof.
- the solvent 13 will include one or more organic compounds, e.g., esters, terpenes, alcohols, ketones, aldehydes, fatty acids, partially or fully esterified fatty acids, wherein the structures are cyclic, non cylcic (e.g., alkyl), alicyclic (i.e., a bridged ring compound), or aromatic, as well as organic compounds having combinations of these functional groups.
- Suitable exemplary solvents 13 are disclosed, e.g., in Aldrich Handbook of Fine Chemicals, 2000-2001 (Milwaukee, WI).
- the solvent 13 includes a polyhydric alcohol, water, or a combination thereof.
- the polyhydric alcohol can be erythritol, propylene glycol, ethylene glycol, Methylene glycol, or a combination thereof. Erythritol is commercially available from Cragill (Minnetonka, Minnesota).
- Additional suitable solvents 13 include, e.g., glycerin; triacetin; diethylene glycol methyl ether; diethylene glycol methyl ether acetate; 1,3-propane diol; 2-methyl-l,3- propane diol; glycerol ricinoleate; PEG-6 caprylic / capric glycerides; caprylic / capric triglycerides; propyleneglycol dicaprylate / dicaprate; glycerol monostearate; glycerol monocaprylate; glycerol monolaurate; neopentyl alcohol; 1-hexadecanol; hydroxypropyl beta-cyclodextrin; vitamin E; vitamin E acetate; deoxycholic acid; taurodeoxycholic acid; 3-[(3-cholamidopropyl) dimethylammonio]-l-propane-sulfonate; BigCHAP; cholic acid; cholesterol NF
- the solvent 13 can be employed in any suitable amount, provided the amount of solvent 13 is effective to dissolve the xanthophylls 15 and/or the pressure sensitive pressure sensitive adhesive 14 and the effective amount of solvent 13 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the solvent 13 can be present in about 1.0 wt% to about 70.0 wt.%; in about 3.0 wt% to about 50.0 wt.%; or in about 5 wt.% to about 30 wt.% of the formulation 5.
- the amount of solvent 13 will depend on the compound or compounds employed as the solvent 13.
- apolyhydric alcohol can be present up to about 70 wt.% of the formulation 5; or in about 20.0 wt.% to about 60.0 wt.% of the formulation 5; and water can be present in about 2.0 wt.% to about 50.0 wt.% of the formulation 5.
- the solvent 13 can be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2.
- the solvent 13 can be located on the entire surface of the front side 3 of the backing 2 or the solvent 13 can be located on a portion of the surface of the front side 3 of the backing 2.
- the solvent 13 can be located on the entire surface of the front side 3 of the backing 2.
- the solvent 13 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the solvent 13 can be partially embedded into the backing 2).
- the solvent 13 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein.
- the solvent 13 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2.
- the solvent 13 can be partially embedded into the backing 2.
- the solvent 13 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the solvent 13 is partially embedded into the backing 2).
- a portion of the front side 3 of the backing 2 can include the solvent 13 and other portions of the front side 3 of the backing 2 can include any combination of the pressure sensitive adhesive 14 and xanthophylls 15.
- the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the solvent 13 can be in continuous contact with the skin surface of the patient.
- the formulation 5 can further include a pressure sensitive adhesive. Any suitable pressure sensitive adhesive 14 can be employed, provided the pressure sensitive adhesive 14 provides the requisite adhesiveness to the adhesive skin patch 1 and the pressure sensitive adhesive 14 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- suitable pressure sensitive adhesives 14 are known to those skilled in the art. Suitable pressure sensitive adhesives 14 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein.
- the pressure sensitive adhesive 14 is an acrylic ester copolymer.
- any suitable amount of pressure sensitive adhesive 14 can be employed, provided the amount of pressure sensitive adhesive 14 effectively provides the requisite adhesiveness to the adhesive skin patch 1 and the effective amount of the pressure sensitive adhesive 14 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the formulation 5 can include a pressure sensitive adhesive 14 in about 0.1 wt.% to about 50 wt.%, in about 0.5 wt.% to about 10.0 wt.%, or in about 1.0 wt.% to about 15.0 wt. % of the formulation 5.
- the suitable amount of pressure sensitive adhesive 14 will depend upon the specific pressure sensitive adhesive 14 employed.
- the pressure sensitive adhesive 14 can include one or more acrylic ester copolymers.
- Each of the one or more acrylic ester copolymers can be present up to about 20.0 wt.% of the formulation 5.
- each of the acrylic ester copolymers can be present up to about 40.0 wt.% of the formulation 5, or up to about 30.0 wt.% of the formulation 5.
- all of the one or more acrylic ester copolymers, when combined, can be present in about 3.0 wt.% to about 40.0 wt.% of the formulation 5, or in about 5.0 wt.% to about 30.0 wt.% of the formulation 5.
- the total amount of acrylic ester copolymers can be about 3.0 wt.% to about 40.0 wt.% of the formulation 5, or about 5.0 wt.% to about 30.0 wt.% of the formulation 5.
- the pressure sensitive adhesive 14 can include a hot melt pressure sensitive adhesive 14 or solvent based pressure sensitive adhesive 14 (e.g., polyacrylate, polyisobutylene, and polybutene), rubber, silicone based pressure sensitive adhesives 14 (e.g., polydimethylsiloxane and resin mixtures), polystyrene-polybutadiene-polystyrene, polystyrene-polyisoprene-polystyrene, polystyrene-poly(ethylene-butylene)-polystyrene block polymers, or any combination thereof.
- solvent based pressure sensitive adhesive 14 e.g., polyacrylate, polyisobutylene, and polybutene
- silicone based pressure sensitive adhesives 14 e.g., polydimethylsiloxane and resin mixtures
- polystyrene-polybutadiene-polystyrene polystyrene-polyisoprene-poly
- the adhesive 14 can include a resin emulsion adhesive, wherein the resin emulsion adhesive can include vinyl acetate resin, acrylic ester copolymer, vinyl acetate/diocyl maleate copolymer, acrylic copolymer, or any combination thereof.
- the resin emulsion adhesive can include vinyl acetate resin, acrylic ester copolymer, vinyl acetate/diocyl maleate copolymer, acrylic copolymer, or any combination thereof.
- the pressure sensitive adhesive 14 can be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the pressure sensitive adhesive 14 can be located on the entire surface of the front side 3 of the backing 2 or the pressure sensitive adhesive 14 can be located on a portion of the surface of the front side 3 of the backing 2. Preferably, the pressure sensitive adhesive 14 can be located on the entire surface of the front side 3 of the backing 2.
- the pressure sensitive adhesive 14 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the pressure sensitive adhesive 14 can be partially embedded into the backing 2). As shown in Figure 9, the pressure sensitive adhesive 14 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No.
- the pressure sensitive adhesive 14 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2. As such, the pressure sensitive adhesive 14 can be partially embedded into the backing 2.
- the pressure sensitive adhesive 14 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the pressure sensitive adhesive 14 is partially embedded into the backing 2).
- a portion of the front side 3 of the backing 2 can include the pressure sensitive adhesive 14 and other portions of the front side 3 of the backing 2 can include the xanthophylls 15.
- the pressure sensitive adhesive 14 being partially embedded into the front side 3 of the backing 2, imparts strength and structure into the adhesive patch 1.
- the pressure sensitive adhesive 14 when the pressure sensitive adhesive 14 is partially embedded into the backing 2, the likelihood that the adhesive patch 1 will tear apart when separated from the release liner 10 or when removed from the skin after use, is minimized.
- the adhesive skin patch 1 When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the pressure sensitive adhesives 14 can be in continuous contact with the skin surface of the patient.
- the formulation 5 or pressure sensitive adhesive 14 can optionally include a compound that emulsifies the formulation 5 or the pressure sensitive adhesive 14.
- a compound that effectively emulsifies the formulation 5 or the pressure sensitive adhesive 14 is pectin.
- the emulsifier e.g., pectin
- the emulsifier can be present in any suitable amount, provided the suitable amount is effective to emulsify the formulation 5 or the pressure sensitive adhesive 14 and the emulsifier remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the emulsifier e.g., pectin
- the emulsifier can be present up to about 30.0 wt.% of the formulation 5, in about 1.0 wt.% to about 20.0 wt.% of the formulation 5, or in about 2.0 wt.% to about 10.0 wt.% of the formulation 5.
- the pressure sensitive adhesive 14 can optionally include one or more polymers 9.
- the polymer 9 provides structure and strength to the pressure sensitive adhesive 14 or provides structure and strength to the formulation 5. Any suitable polymer 9 can be employed, provided the polymer 9 provides structure and strength to the pressure sensitive adhesive 14 or provides structure and strength to the formulation 5, and the polymer 9 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- Suitable polymers 9 include natural polymers and synthetic polymers.
- the polymer 9 can include, e.g., karaya, a polyacrylamide, xanthum gum, guar gum, a hydrophilic polymer, a hydrocolloidal polymer, starch, a starch derivative, vinyl acetate copolymer, polyvinyl pyrrolidone, polyethylene oxide, algin, a derivative of algin, a polyacrylate, gelatin, polymaleic acid, polyacrylic acid, polymaleic anhydride, a polyurethane, a polyurea, gum acacia, locust bean gum, modified guar gum, maltodextrin, carboxymethyl cellulose, carboxypropyl cellulose, polyvinyl alcohol, poly AMPS, or a combination thereof.
- polymers 9 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein.
- the polymer 9 can include polyacrylamide, karaya, or a combination thereof. Any suitable amount of polymer 9 can be employed, provided the amount of polymer 9 effectively provides structure and strength to the pressure sensitive adhesive 14 or to the formulation 5, and the effective amount of polymer 9 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the suitable amount of polymer 9 will depend upon the specific polymer 9 employed.
- karaya can be employed as the polymer 9 up to about 60 wt.% of the formulation 5, in about 5.0 wt.% to about 45 wt.% of the formulation 5, or in about 8.0 wt.% to about 40 wt.% of the formulation 5; polyacrylamide can be employed as the polymer 9 up to about 40 wt.% of the formulation 5, in about 5.0 wt.% to about 35 wt.% of the formulation 5, or in about 8.0 wt.% to about 30 wt.% of the formulation 5; or both karaya and polyacrylamide can be employed as the polymer 9, wherein karaya is present in about 5.0 wt.% to about 35 wt.% of the formulation 5 and polyacrylamide is present in about 5.0 wt.% to about 30 wt.% of the formulation 5.
- Humectant The formulation 5 can optionally include one or more humectants 17 to provide a moistening effect to the pressure sensitive adhesive 14.
- the humectant 17 can optionally hydrate the polymer 9. Any suitable humectant 17 can be employed, provided the humectant 17 effectively provides a moistening effect to the pressure sensitive adhesive 14 and the humectant 17 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- One suitable humectant 17 is glycerin.
- Other suitable humectants 17 include polyhydric alcohols such as ethylene glycol, propylene glycol, Methylene glycol, tetraethylene glycol, sorbitol, and combinations thereof.
- any suitable amount of humectant 17 can be employed, provided the amount of humectant 17 effectively provides a moistening effect to the pressure sensitive adhesive 14 and the amount of humectant 17 effectively remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the suitable amount of humectant 17 will depend upon the specific humectant 17 employed and the specific polymer 9 employed.
- karaya, polyacrylamide, or a combination thereof can be employed as the polymer 9 and glycerin can be employed as the humectant 17, wherein the glycerin is present in about 25.0 wt.% to about 70.0 wt.% or in about 40.0 wt.% to about 55.0 wt.% of the formulation 5.
- the formulation 5 can optionally include one or more fillers 6. Any suitable filler 6 can be employed. Suitable fillers 6 include malto dextrin, dextrin, 70% sorbitol water, modified starches, depolymerized starches, and methylcellulose. As used herein, "malto dextrin” is a dextrose equivalent, wherein dextrose is D-glucose. Malto dextrin is commercially available as Amaizo Lodex 5 from American Maize-Products (Hammond, IN). Any suitable amount of filler 6 can be employed in the formulation 5. The suitable amount of filler 6 can depend in part upon the specific filler present in the formulation 5. For example, malto dextrin can be present up to about 20.0 wt.% of the formulation 5, or in about 1.0 wt.% to about 10.0 wt.% of the formulation 5.
- the formulation 5 can optionally include a skin protectant 18 (i.e., topical moisturizer or skin conditioner).
- a skin protectant 18 i.e., topical moisturizer or skin conditioner.
- Any suitable skin protectant 18 can be employed, provided the skin is effectively protected or moisturized and the skin protectant remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the skin conditioner is medicinally acceptable for topical use in humans.
- Suitable topical moisturizers 18 include, e.g. calamine, aloe, lanolin, glycerin, Vitamin E, Vitamin E acetate, farnesol, glycyrrhetinic acid, aluminum hydroxide gel, cocoa butter, propylene glycol, ethylene glycol, Methylene glycol, hard fat, kaolin, mineral oil, petrolatum, topical starch, white petroleum, cod liver oil, shark liver oil, zinc oxide, or any combination thereof. Additional suitable topical moisturizers 18 are disclosed, e.g., in U.S. Patent Nos. 6,096,334; 6,096,033; 5,741,510; 5,536,263; 4,675,009; 4,307,717; 4,274,420; 5,976,565; 5,536,263; and references cited therein.
- aluminum hydroxide gel refers to a suspension containing aluminum oxide (A12O3), mainly in the form of a hydroxide. It is typically obtained by drying the product of interaction in aqueous solution of an aluminum salt with ammonium or sodium carbonate.
- cocoa butter refers to a fatty substance in cocoa beans; a thick oily solid obtained from cocoa beans and used in making chocolate, cosmetics, and suntan oil. Also known as threobroma oil, it lubricates and softens the skin.
- topical starch refers to cornstarch.
- Kaolin refers to aluminum silicate; powdered and freed from gritty particles by elutriation. Kaolin refers to the name of the locality in China where the substance is found in abundance.
- white petroleum refers to a purified mixture of hydrocarbons obtained from petroleum.
- a bleached version of yellow soft paraffin it is used as an emollient and as a base for ointments. It is odorless when rubbed into the skin and not readily absorbed.
- mineral oil refers to the heavy liquid petrolatum; liquid paraffin or petroleum; a mixture of liquid hydrocarbons obtained from petroleum, and is typically used as a vehicle in medicinal preparations.
- petrolatum refers to petroleum jelly; a yellow soft paraffin; a yellowish mixture of the softer members of the paraffin or methane series of hydrocarbons, obtained from petroleum as an intermediate product in the distillation; typically used as a soothing application to burns and abrasions of the skin, and as a base for ointments.
- cod liver oil refers to the partially destearinated fixed oil extracted from the fresh livers of Gadus morrhuae and other species of the family Gadidae, containing Vitamins A and D.
- shk liver oil refers to the oil extracted from the livers of sharks, mainly of the species Hypoprion brevirostris; a rich source of Vitamins A and D.
- zinc oxide refers to ZnO, which is typically used as a protective ointment.
- calamine is a pink powder of zinc oxide and a skin protectant containing about 98% zinc oxide and about 0.5% ferric oxide
- aloe is the dried latex of leaves of Curaco Aloe (Aloe barbadenis Miller, Aloe vera Linne) or Cape Aloe (Aloe ferox Miller and hybrids), of the family Liliacaea. Aloe is commercially available as Aloe Vera Gel from Terry Laboratories (Melbourne, FL).
- Aloe Vera Gel is commercially available as Aloe Vera Gel 4OX (20.0 wt.% solution in water), Aloe Vera Gel IX (0.5 wt.% solution in water), Aloe Vera Gel 1OX (5.0 wt.% solution in water), or solid Aloe Vera.
- the solid Aloe Vera can be dissolved in a carrier, such as water, to the desired concentration.
- the commercially available forms of Aloe Vera are optionally available as decolorized Aloe Vera.
- Vitamin E is 3,4-dihydro-2,5,7,8-tetramethyl-2- (4,8,12-trimethyltridecyl)-2H-l-benzo ⁇ yran-6-ol
- Vitamin E acetate is 3,4- dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-l-benzopyran-6-ol acetate
- lanolin is the fat-like secretion of the sebaceous glands of sheep (i.e., complex mixture of esters and polyesters of 33 high molecular weight alcohols and 36 fatty acids) which is deposited onto the wool fibers
- farnesol is 3,7,11- trimethyl-2,6,10-dodecatrien-l-ol.
- Farnesol is commercially available from American Radiolabeled Chemicals (ARC) (St. Louis, MO), and "glycyrrhetinic acid” is a pentacyclic triterpenoid derivative of the beta-amyrin type and is shown below:
- any suitable amount of skin protectant 18 can be employed, provided the suitable amount of skin protectant 18 effectively protects or moisturizes the skin and the effective amount of skin protectant 18 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the amount of skin conditioner employed is medicinally acceptable for topical use in humans.
- the skin protectant 18 can be present up to about 20.0 wt.%, up to 10.0 wt.%, up to 5.0 wt.%, or up to 2.0 wt.% of the formulation 5.
- the suitable and effective amount of skin protectant 18 will depend in part upon the specific skin protectant 18 present in the formulation 5.
- Aloe Vera Gel, 1OX can be present up to about 20.0 wt.% of the formulation 5, up to about 10.0 wt.% of the formulation 5, up to about 5.0 wt.% of the formulation 5, or up to about 1.0 wt.% of the formulation 5.
- Vitamin E acetate can be present up to about 10.0 wt.% of the formulation 5, up to about 5.0 wt.% of the formulation 5, up to about 3.0 wt.% of the formulation 5, up to about 2.0 wt.% of the formulation 5, or up to about 1.0 wt.% of the formulation 5.
- the skin conditioner will be present in an amount that is consistent with any State or Federal regulations.
- the skin protectant 18 can be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the skin protectant 18 can be located on the entire surface of the front side 3 of the backing 2 or the skin protectant 18 can be located on a portion of the surface of the front side 3 of the backing 2. Preferably, the skin protectant 18 can be located on the entire surface of the front side 3 of the backing 2.
- the skin protectant 18 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the skin protectant 18 can be partially embedded into the backing 2).
- the skin protectant 18 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein.
- the skin protectant 18 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2.
- the skin protectant 18 can be partially embedded into the backing 2.
- the skin protectant 18 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the skin protectant 18 is partially embedded into the backing 2).
- a portion of the front side 3 of the backing 2 can include the skin protectant 18 and other portions of the front side 3 of the backing 2 can include any combination of the solvent 13, pressure sensitive adhesive 14, and xanthophylls 15.
- the adhesive skin patch 1 When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the skin protectant 18 can be in continuous contact with the skin surface of the patient.
- the formulation 5 can optionally include a preservative 7 that is useful for preventing bacterial growth, mold growth, fermentation, and/or decomposition.
- preservative refers to any substance which prevents bacterial growth, mold growth, fermentation, and/or decomposition. Concise Chemical and Technical Dictionary, 4th enlarged edition, Chemical Publishing Co., Inc., NY, NY p. 939 (1986). Any suitable preservative 7 can be employed, provided the preservative 7 effectively prevents bacterial growth, mold growth, fermentation, and/or decomposition; and the preservative 7 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 2 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- Suitable preservatives 7 include, e.g., quat-15, parabens, dichlorobenzyl alcohol, ethylene diamine tetreacetic acid, formaldehyde, gum benzoin, imidazolidinyl urea, phenyl-mercuric acetate, poly aminopropyl biguanide, proply gallate, sorbic acid, cresol, chloroacetamide sodium benzoate, chloromethyl-methylisothiazolinone, chloromethyl-methylisothiazolon, chloromethyl-methylisothiazolinone benzalkonium chloride, an.
- octylisothiazolinone benzimidazol-compound, chloromethyl- methylisothiazolinone octylisothiazolinone, o-phenylphenol benzisothiazolinone, o-phenylphenol benzisothiazolinone, benzisothiazolinone, an aliphatic amine of 2-thiopyridineoxide, benzoic acid, editic acid, phenolic acid, benzyl alcohol, isopropyl alcohol, benzenethonium chloride, bronopol, cetrimide, chlorohexidine, chlorobutanol, chlorocresol, phenol, phenoxyethanol, phenyl ethyl alcohol, phenylmercuric acetate, phenyhnercuric borate, phenylmercuric nitrate, potassium sorbate, proplyene glycol, sodium benzoate, sodium propionate, thimerosol,
- the preservative is quat-15, which is commercially available from Dow Chemical (Midland Michigan); methyl paraben; ascorbic acid; or a combination thereof.
- the preservative 7 can be employed in any suitable amount provided the amount of preservative 7 effectively prevents bacterial growth, mold growth, fermentation, and/or decomposition and the effective amount of preservative 7 remains stable in the formulation 5.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced hi the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- the preservative 7 can be present up to about 99.9 wt.
- preservative 7 present in the formulation 5 will typically depend upon the specific compound or compounds employed as the preservative 7.
- quat-15 can be employed in about 0.01 wt.% to about 1.5 wt.% of the formulation 5, in about 0.05 wt.% to about 0.15 wt.% of the formulation 5, or in about 0.08 wt.% to about 0.12 wt.% of the formulation 5.
- the formulation 5 can include xanthophylls 15 that is not soluble and/or stable either without a solvent or with the specific solvent 13, in the amount employed.
- a complexing agent can be employed to modulate (i.e., regulate) the solubility, stability, and/or the volatility of the xanthophylls 15 in the formulation 5.
- Any suitable complexing agent can be employed, provided the complexing agent effectively solubilizes and/or stabilizes the xanthophylls 15 and the complexing agent remains stable in the formulation 5 over a prolonged period of time.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
- any suitable amount of complexing agent can be employed, provided the amount of complexing agent effectively solubilizes and/or stabilizes the xanthophylls 15 and the amount of complexing agent remains stable in the formulation 5 over a prolonged period of time.
- Suitable specific complexing agents include, e.g., cyclodextrins.
- a "cyclodextrin” refers to a non-reducing cyclic oligosaccharide with at least 6 anhydro glucose units linked by alpha 1,4 bonds to form a ring.
- Cyclodextrins are typically produced by the action of the enzyme cyclodextrin glucosyltransferase [CGT-ase] on starch.
- the most common cyclodextrins include alpha, beta, and gamma cyclodextrins, which have six, seven, or eight, respectively, anhydroglucose units in the ring structure.
- cyclodextrins All of the hydroxyl groups in cyclodextrins are oriented to the outside of the ring while the glucosidic oxygen and two rings of the non-exchangeable hydrogen atoms are directed towards the interior of the cavity. This combination gives cyclodextrins a hydrophobic inner cavity and a hydrophilic exterior. See, e.g., the Cerestar website (http://www.cerestar.com); the Betadexcyclodextrin website (http://www.betadexcyclodextrin.com); and M. L. Bender and M. Komiyama, Cyclodextrin Chemistry, Springer, Berlin, 1978.
- Cyclodextrins are enzymatically-modified starches formed by the action of the enzyme cyclodextrin glucosyltransferase on starch. They are doughnut- shaped molecules, which can interact with organic molecules to form complexes. It is also possible for some organic molecules and some inorganic salts to associate with the hydroxyl groups of the cyclodextrin. Three cyclodextrins are typically formed, alpha, beta, and gamma cyclodextrin, which contain six, seven, or eight glucose molecules in the ring, respectively. The electron-dense glycosidic oxygen atoms are oriented inward and line the cavity. The hydroxyl groups are directed toward the outside of the ring.
- hydrophilic groups interact with the water to give the cyclodextrins their aqueous solubility properties.
- the hydrogen and glycosidic oxygen atoms lining the cavity give the cyclodextrin molecule its hydrophobic character and its ability to interact with organic molecules to form complexes. Because of the free rotation of the C-6 carbon, this end of the cyclodextrin cavity is narrower than the end with the C-2 and C-3 hydroxyls.
- Derivatives of cyclodextrin can be obtained, e.g., by replacing one or more hydroxyl groups with a suitable radical (i.e., pendant group).
- Suitable pendant groups include, e.g., sulfmyl; sulfonyl; phosphate; (d-C 12 )alkyl optionally substituted with one or more (e.g., 1, 2, 3, or 4) hydroxy, carboxy, carbonyl, acyl, oxy, oxo; or a combination thereof.
- Suitable specific pendant groups include methyl, ethyl, hydroxypropyl, carboxymethyl, sulfate, phosphate, and an acrylate.
- the specific pendant group can include (C 1 - C 12 )alkoxy optionally substituted with one or more hydroxy.
- cyclodextrin examples include, e.g., alpha- cyclodextrin sulfate, beta-cyclodextrin sulfate, gamma-cyclodextrin sulfate, alpha-hydroxypropyl cyclodextrin, beta-hydroxypropyl cyclodextrin, gamma- hydroxypropyl cyclodextrin, alpha-cyclodextrin phosphate, beta-cyclodextrin phosphate, and gamma-cyclodextrin phosphate.
- Cyclodextrins are starches that have been specially modified by the action of an enzyme to make a water-soluble ring-shaped molecule, capable of holding another, oil-like organic substance in its 'cavity'. Because of this unique property, cyclodextrins can be used to carry all kinds of active ingredients (e.g., drugs, fragrances, flavors, and vitamins) in a wide variety of formulations. Increased stability, water solubility, and controlled release are among the many application benefits. Specifically, cyclodextrins have the benefit of encapsulating a substance, thereby providing protection for the substance. This results in increased shelf-life and a reduced loss of degradation or decomposition. Cyclodextrins are themselves soluble in water, and can greatly increase the solubility of highly water insoluble substances, m addition, cyclodextrins can be used to control the release of a substance.
- active ingredients e.g., drugs, fragrances, flavors, and vitamins
- Suitable cyclodextrins include alpha cyclodextrins, beta cyclodextrins, and gamma cyclodextrins.
- the cyclodextrin can be hydroxylpropyl beta cyclodextrin, hydroxylproplyl alpha cyclodextrin, or a combination thereof.
- the cyclodextrin can optionally be branched. Suitable cyclodextrins, and derivatives thereof, can be found, e.g., at U.S.
- the formulation 5 can further include a penetration enhancer effective to improve the penetration of the xanthophylls into and through bodily tissue (e.g., skin), with respect to a formulation 5 lacking the penetration enhancer.
- the penetration enhancer may generally be any penetration enhancer.
- Suitable penetration enhancers include, e.g., diethylene glycol monoethyl ether (transcutol), dimethyl sulfoxide (DMSO), propyleneglycol, ionic surfactants, non-ionic surfactants, anionic surfactants, isopropyl myristate (DPM), calcipotriene, detergents, emollients, chelators (e.g., calcium chelators such as EDTA, EGTA), and combinations thereof.
- enhancers include Loramide DEA, Ethoxydiglycol, NMP, Triacetin, Propylene Glycol, Benzyl Alcohol, Sodium Laureth Sulfate, Dimethyl Isosorbide, Isopropyl Myristate, Olive Squalane, Medium Chain Triglyceride Oil (MCT Oil), Menthol, Isopropyl Palmitate, Isopropyl Isostearate, Propylene Glycol Monostearate, Lecithin, Diisopropyl Adipate, Diethyl Sebacate, Oleic Acid, Ethyl Oleate, Urea, Glyceryl Oleate, Caprylic/Capric Triglyceride, Propylene Glycol Dicaprylate/Dicaprate, Laureth -4, Oleth-2, Oleth-20, Propylene Carbonate, Nonoxynol-9, 2-n-nonyl-l,3- dioxolane, C7 to C14-hydrocarby
- the skin absorption enhancer can include diethylene glycol monoethyl ether (transcutol).
- diethylene glycol monoethyl ether or “transcutol” refers to 2-(2- ethoxyethoxy)ethanol [CAS NO. 001893].
- the penetration enhancer can be present in the formulation 5 in any suitable and appropriate amount (e.g., between about 1 wt.% and about 10 wt.%).
- the formulation 5 can further include a keratolytic agent.
- keratolytic agent refers to a substance that causes desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis. Any suitable keratolytic agent can be employed, preferably the keratolytic agent effectively causes desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis.
- the keratolytic agent is pharmaceutically acceptable for topical use on humans. Suitable keratolytic agents include, e.g., alcloxa, resorcinol, or a combination thereof.
- alcloxa refers to Al-chlorhydroxy allontoinate
- resorcinol refers to m-dihydroxybenzene or 1,3-benzenediol. Any suitable and effective amount of keratolytic agent can be employed, provided the amount of keratolytic agent effectively causes desquamation
- the keratolytic agent can include an amount of alkaline material (e.g., potassium hydroxide (KOH), sodium hydroxide (NaOH), etc.), effective to cause desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis.
- alkaline material e.g., potassium hydroxide (KOH), sodium hydroxide (NaOH), etc.
- KOH potassium hydroxide
- NaOH sodium hydroxide
- the desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis can be achieved with the use, e.g., of mechanical stripping, tape, etc.
- the desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis can be achieved with the use, e.g., of radiant energy such as ultrasound, heat, etc., or with the use of photodynamic therapy.
- the formulation 5 can further include a topical acne drug 15, useful to treat acne.
- the topical acne drug 15 can be present in any appropriate and suitable amount, provided the amount of topical acne drug 15 is effective to treat and/or prevent acne or a pimple and the amount of topical acne drug 15 remains stable in the formulation 5 over a prolonged period of time.
- the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the patch 1.
- the topical acne drug 15 can be present in about 0.01 wt.% to about 99.9 wt.% of the formulation 5.
- the amount of topical acne drug present in the formulation 5 can be up to about 5.0 wt.% of the formulation 5, up to 4.0 wt.% of the formulation 5, up to 3.0 wt.% of the formulation 5, or in about 0.5 wt.% to about 2.0 wt.% of the formulation 5.
- the topical acne drug 15 and amount thereof will comply with FDA regulations (e.g., 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, April 1, 2000 Edition).
- the amount of topical acne drug 15 present in the formulation 5 will typically depend upon the specific compound or compounds employed as the topical acne drag 15.
- salicylic acid can be present up to about 99.9 wt.% of the formulation 5, up to about 10.0 wt.% of the formulation 5, up to 2.0 wt.% of the formulation 5, or up to about 2.0 wt.% of the formulation 5.
- resorcinol can be present up to about 2 wt.% of the formulation 5, in accordance with 21 CFR Ch.l, ⁇ 333.320(a) and 333.310(a).
- resorcinol monoacetate can be present up to about 3 wt.% of the formulation 5, in accordance with 21 CFR Ch.l, ⁇ 333.320(b) 333.310(b).
- salicylic acid can be present in about 0.5 wt.% to about 2.0 wt.% of the formulation 5, in accordance with 21 CFR Ch.l, ⁇ 333.310(c).
- sulfur can be present in about 3.0 wt.% to about 10.0 wt.% of the formulation 5, in accordance with 21 CFR Ch.l, ⁇ 333.310(d).
- the topical acne drug 15 can preferably be located on and in any portion of the formulation 5, which is located on the front side 3 of the backing 2.
- the topical acne drug 15 can be located on and in the entire portion of the formulation 5.
- the topical acne drug 15 can be located on the entire surface of the front side 3 of the backing 2 or the topical acne drag 15 can be located on a portion of the surface of the front side 3 of the backing 2.
- the topical acne drag 15 can be located on the entire front side 3 of the backing 2.
- the topical acne drag 15 can be located in at least a portion of the front side 3 of the backing 2 (i.e., the topical acne drag 15 can be partially embedded into the backing 2).
- the topical acne drag 15 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein.
- the topical acne drag 15 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one- fourth to about nine-tenths the thickness of the backing 2. As such, the topical acne drag 15 can be partially embedded into the backing 2.
- the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human)
- the topical acne drug 15 can be in continuous contact with the skin surface of the patient.
- an adhesive skin patch 1 is provided in which the formulation 5 does not include xanthophylls 15.
- the adhesive skin patch 1 can be manufactured, shipped, and stored without xanthophylls 15, and an xanthophylls 15 can be introduced to the adhesive skin patch 1 at a later time.
- the formulation 5 can preferably remain stable over the period of time typically experienced with the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1, e.g., up to about a month, up to about a year, up to about two years, or up to about 3 years.
- the stability of the xanthophylls 15, for example, is due in part to the formulation 5 including the xanthophylls 15 in an adhesive formulation.
- the adhesive formulation is preferably a hydrogel that holds the xanthophylls 15 in an available form while maintaining the necessary stability, pressure sensitive adhesion and effectiveness over a prolonged period of time, e.g., up to about a month, up to about a year, up to about two years, or up to about 3 years.
- the adhesive skin patch 1 can have any suitable size and shape.
- the adhesive skin patch 1 can be cut, as desired, to provide an adhesive skin patch 1 of a desired size and shape.
- the adhesive skin patch 1 can be cut with any suitable cutting device such as a scissors, scalpel, or knife.
- the adhesive skin patch 1 can have any suitable length.
- the patch can be a self- wound roll 25 without a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. See, e.g., Figure 10.
- the adhesive skin patch 1 can have a length of about 12 inches to about 100 yards, about 10 feet to about 50 yards, or about 20 feet to about 20 yards.
- the adhesive skin patch 1 can have a width of about 0.1 inch to about 5.0 inches, about 0.1 inch to about 1.0 inch, or about 0.1 inch to about 0.5 inch.
- the adhesive skin patch 1 can be rectangular and can have a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1.
- the adhesive skin patch 1 can typically have a length of up to about 10 inches, up to about 6 inches, up to about 4 inches, or up to about 2 inches.
- the adhesive skin patch 1 can have any suitable width.
- the adhesive skin patch 1 will have a width of up to about 5 inches, up to about 2.5 inches, up to about 1 inch, or up to about 0.5 inch.
- the adhesive skin patch 1 can have any suitable thickness.
- the adhesive skin patch 1 will have a thickness of about 0.10 mm to about 2.0 mm, about 0.15 mm to about 1.0 mm, or about 0.20 mm to about 0.75 mm.
- the adhesive skin patch 1 can be crescent, oval or circular in shape.
- the circular adhesive skin patch 1 can have a diameter of about 0.1 inch to about 10 inches.
- the circular adhesive skin patch 1 can have a diameter of about 1.5 inches to about 5 inches. See, Fig. 7.
- the adhesive skin patch 1 can be rectangular in shape.
- the rectangular adhesive skin patch 1 can have a length of about 1 inch to about 10 inches and a width of about 1 inch to about 10 inches.
- the rectangular adhesive skin patch 1 can have a length of about 1 inch to about 2 inches and a width of about 0.1 inch to about 0.75 inch. See, Fig. 8.
- the adhesive skin patch 1 can have a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1.
- one or more adhesive skin patches 1 can be mounted on the release liner 10.
- one adhesive skin patch 1 can have one release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1.
- about 2 to about 100 or about 2 to about 20 adhesive skin patches 1 can be mounted on the release liner 10.
- the cost of having two or more patches 1 on a single release liner 10 is typically less expensive than skin patches 1 that are separately mounted on a single release liner 10.
- some consumers may prefer the ease and comfort of carrying a single patch assembly that includes a single release liner 10 and more than one (e.g., about 2 to about 20, or about 2 to about 10) adhesive patches 1 mounted on the single release liner 10.
- the adhesive skin patch 1 can be applied to any suitable skin surface of the patient.
- the adhesive skin patch 1 when used to treat topical skin disorders (e.g., wrinkles, acne, etc.), the adhesive skin patch 1 can be applied to that surface of the skin that is afflicted with the topical skin disorder.
- the adhesive skin patch 1 can locally deliver a cosmetically and/or therapeutically effecteive amount of xanthophylls 15.
- the adhesive skin patch 1 when the adhesive skin patch 1 is used to treat other disorders (e.g., macular degeneration, angiogenesis, cancer, heart disease, and diabetes), the adhesive skin patch 1 can be applied to any topical skin surface, for systemic delivery of the xanthophylls 15.
- the adhesive patch 1 of the present invention can be formulated or manufactured employing the above components.
- the adhesive patch 1 of the present invention can be formulated or manufactured using any suitable technique.
- the adhesive patch 1 can be formulated or manufactured as described herein or as described in U.S. Patent No. 5,536,263; U.S. Patent No. 5,741,510; and references cited therein; wherein the backing can be treated with a sizing agent 8 prior to the infusion of the formulation 5.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
Abstract
The present invention provides for an adhesive patch that includes a flexible backing having a front side and a back side and a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. The formulation includes xanthophylls, a solvent that dissolves the xanthophylls, and a pressure sensitive adhesive. The present invention also provides methods of using the adhesive patch (e,.g., treating acne or a pimple in a mammal; exfoliating the skin surface of a mammal; and/or improving the appearance of skin surface in a mammal). The methods include applying the adhesive patch of the present invention to a topical (e.g., skin) surface of a patient.
Description
TOPICAL SKIN PATCH
Background of the Invention
Acne vulgaris is a chronic disorder of the pilosebaceous follicles (apparatus) characterized by comedones (blackheads), papules, pustules, cysts, nodules, and often scars, that appear on the most visible areas of the skin (e.g., the face, chest, back, neck, and upper arms). The pilosebaceous apparatus is largely under the control of endogenous hormones (mainly androgens) which are present in unusually high concentrations in the blood during adolescence and puberty, giving rise to an excessive production of sebum. The condition may worsen by a simultaneous increase in the rate of keratinization of the skin's horny layer (the stratum corneum). As the horny cells proliferate, they can form an occlusive plug or comedone which coupled with the increased production of the sebum, represents an ideal medium for the proliferation of the skin resident strains, such as the Gram positive anaerobic bacterium, Propionibacterium acnes. Eventually, the plugged follicles rupture and allow the discharge of their contents, causing local swelling and inflammation. The exposed follicles may darken from the deposition of pigment from damaged cells in the deeper layer of skin. In severe cases, acne can lead to hospitalization of the patient, extensive discomfort, and long term scarring of the skin.
There are numerous treatments available for treating acne. Typically, acne is treated with topical compositions in the form of creams, gels, emulsions or lotions that contain selected agents. These agents include hormones or hormone agonists and antagonists (EP Al 0 563 813 and U.S. Patent No. 5,439,923), antimicrobial agents (U.S. Patent No. 4,446,145, GB 2,088,717, GB 2,090,135, GB 1,054,124, U.S. Patent No. 5,409,917), salicylic acid (U.S. Patent No. 4,514,385, U.S. Patent No. 4,355,028, EP Al 0 052 705, FR-A 2,581,542, and FR-A 2,607,498).
Oral administration of acne drugs is currently provided for severe cases of acne. These are reviewed in "Acne, A Review of Optimum Treatment" by Sykes N. I. and Webster G. F in Drugs 48, 59-70 (1994). Numerous side-effects have been described using oral administration of acne drugs. For example,
isotretinoin, which is a derivative of vitamin A has associated risks of teratogenicity and may be a risk for women of childbearing age. Oral administration of antibiotics suited for treating acne may induce the appearance of adverse effects which include abdominal cramps, black tongue, cough, diarrhea, fatigue, irritation of the mouth and other undesirable symptoms.
FDA regulations (e.g., 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, April 1, 2000 Edition) regulate what components (i.e., "active ingredients"), in a specified amount, may be described as treating acne (i.e., contains a topical acne drug). In order to follow FDA regulations, therefore, only a select number of active ingredients that are able to treat acne, in a specified amount, may be included in a composition when the composition is described as treating acne. Consequently, it is difficult to manufacture a composition that includes a topical acne drug, while at the same time maintaining (a) the solubility and stability of the active ingredients in the composition and (b) following FDA regulations.
There is a need therefore for new methods and composition for treating patients with acne that have minimum adverse effects, have maximum efficacy, may be simple and comfortable to use, administers to the skin an effective and known amount of a topical acne drug, and complies with FDA regulations. There is a need therefore for methods and devices for treating patients with acne that have minimum adverse effects, have maximum efficacy, may be simple and comfortable to use, administers to the skin an effective and known amount of a topical acne drug, and complies with FDA regulations. The device will preferably be an adhesive patch that effectively controls the rate of penetration and/or effectively controls the depth to which the ointment or gel will penetrate before solidifying.
Accordingly, what is needed is a device that includes effective amounts of xanthophylls. The device will include a known, discrete, safe, and effective amount of xanthophylls. The device will maintain the stability of the xanthophylls over an extended period of time. The device will also be convenient to use. Additionally, the device will allow for the treatment of topical skin disorders (e.g., wrinkles, skin cancer and acne), as well as the treatment of other disorders (e.g., macular degeneration, angiogenesis, cancer,
heart disease, and diabetes), utilizing xanthophylls in a known, safe, efficient, and convenient manner.
Summary of the Invention The present invention provides for the use of an adhesive patch in preventing and/or treating topical skin disorders (e.g., wrinkles and acne), as well as the treatment of other disorders (e.g., macular degeneration, angiogenesis, cancer, heart disease, and diabetes). The adhesive patch includes xanthophylls in a known, discrete, safe, and effective amount. The adhesive patch maintains the stability of the xanthophylls over an extended period of time. The adhesive patch is also convenient to use.
The present invention provides for an adhesive patch that includes a flexible backing having a front side and a back side and a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. The formulation includes xanthophylls, a solvent that dissolves the xanthophylls, and a pressure sensitive adhesive.
The present invention also provides an adhesive patch that includes a flexible backing having a front side and a back side and a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. The formulation includes xanthophylls and a hot melt adhesive. The present invention also provides a method of locally delivering xanthophylls to a topical skin surface. The method includes topically applying to a skin surface an adhesive patch of the present invention, for a period of time effective to locally deliver xanthophylls to the topical skin surface.
A method of systemically delivering xanthophylls to a mammal. The method includes topically applying to a skin surface an adhesive patch of the present invention, for a period of time effective to systemically deliver xanthophylls to the mammal.
The present invention also provides a method for treating or preventing acne or a pimple in a mammal in need thereof. The method includes applying to the skin surface of the mammal having the acne or the pimple or the skin surface
of the mammal at risk thereof an adhesive patch of the present invention, for an effective period of time to effectively treat or prevent acne or a pimple.
The present invention also provides a method for exfoliating the skin surface of a mammal. The method includes applying to the skin surface of the mammal in need of such exfoliating an adhesive patch of the present invention, for an effective period of time and removing the adhesive patch, thereby effectively exfoliating the skin surface.
The present invention also provides a method for improving the appearance of skin surface in a mammal. The method includes applying to the skin surface of the mammal in need of such appearance improvement, the adhesive patch of the present invention, for an effective period of time to effectively improve the appearance of the skin surface.
The present invention also provides an adhesive patch of the present invention for use in medical therapy. The present invention also provides the use of an adhesive patch of the present invention for the manufacture of a medicament for treating a topical skin condition.
The present invention also provides the use of an adhesive patch of the present invention for the manufacture of a medicament for treating treating acne in a mammal, treating pimples in a mammal, improving the appearance of skin surface of a mammal, or any combination thereof.
Brief Description of the Figures
Embodiments of the invention may be best understood by referring to the following description and accompanying drawings which illustrate such embodiments. The numbering scheme for the Figures included herein are such that the leading number for a given reference number in a Figure is associated with the number of the Figure. For example, an adhesive patch 1 can be located in Figure 1. However, reference numbers are the same for those elements that are the same across different Figures. In the drawings:
Figure 1 illustrates the front side of an adhesive patch useful in the present invention.
Figure 2 illustrates the back side of an adhesive patch useful in the present invention.
Figure 3 illustrates the front side of an adhesive patch useful in the present invention, with a release liner attached to the patch.
Figure 4 illustrates the back side of an adhesive patch useful in the present invention, with a release liner attached to the patch. Figure 5 illustrates the back side of an adhesive patch useful in the present invention, with a release liner attached to the patch and the patch is partially detached from the release liner.
Figure 6 illustrates the back side of an adhesive patch useful in the present invention, with a release liner attached to the patch and the patch is partially detached from the release liner.
Figure 7 illustrates a top view of a specific patch useful in the present invention.
Figure 8 illustrates a top view of a specific patch useful in the present invention. Figure 9 illustrates a specific adhesive skin patch useful in the present invention, wherein the patch is in use.
Figure 10 illustrates an enlarged cross-sectional view of a specific patch useful in the present invention.
Detailed Description of the Invention
The present invention provides for an adhesive patch, and for the cosmetic and pharmaceutical uses of the adhesive patch. The adhesive patch includes xanthophylls in a known, discrete, safe, and effective amount. The adhesive patch maintains the stability of the xanthophylls over an extended period of time. The adhesive patch is also convenient to use.
References in the specification to "one embodiment", "an embodiment", "an example embodiment", etc., indicate that the embodiment described may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described.
The present invention provides a unique adhesive vehicle. The vehicle has pressure sensitive adhesive qualities due to its composition and viscoelastic nature. The adhesive is hydrophilic and therefore water can dissolve into or evaporate from the adhesive, depending on the conditions to which it is exposed. This water exchange capability implies that if the adhesive is on a suitably porous backing and is applied to the skin, it will not be necessarily be occlusive, as most drug delivery patches are. The occlusive nature of conventional drug delivery patches is thought to play an important role in enhancing drug absorption, but also often results in greater incidence of skin irritation. In one embodiment of the invention, the relatively low occlusiveness of the adhesive skin patch can be envisioned to be a special adhesive ointment or gel which is water-breathable, such as a water washable or water soluble ointment or gel. The present invention provides an ointment or gel on a backing. The ointment or gel includes xanthophylls in a known, discrete, safe, and effective amount. The adhesive patch maintains the stability of the xanthophylls over an extended period of time. The backing is pliable and/or stretchable. Since the backing can either be porous/vapor permeable or non-porous/vapor impermeable, many consumers typically refer to the device as a "patch," a "skin patch," or an "adhesive skin patch." As such, the device (i.e., the ointment or gel on the backing) will herein be referred to as a patch, a skin patch, an adhesive skin patch. It is appreciated that those skilled in the art understand that the term "patch" is used to refer to the device and is not otherwise limiting in any manner.
It is appreciated that those of skill in the art understand that the terms used herein, unless expressly stated otherwise, include the singular as well as the plural. For example, the term "xanthophylls" 15 includes the singular (i.e., one xanthophyll) as well as the plural (i.e., two or more xanthophylls).
As used herein, "holdout" refers to the physical properties of a backing, relating to the ability of a specific class of gels or ointments to penetrate, crosslink, wet, and/or cure within the matrix of the backing. A specific class of gels or ointments may or may not be able to penetrate a given backing. Upon penetration of a gel or ointment into a backing, the gel or ointment will crosslink, wet, or cure in the backing. As such, the holdout properties are the ability of the gel or ointment to affect the degree of penetration, cross-linking, wetting, and/or curing within the matrix of the backing. Those backings with superior
holdout properties will typically prevent, decrease, or lessen the likelihood of the ointment or gel from wetting the backing; will typically increase the likelihood of the ointment or gel to cross-link within the matrix of the backing; will typically increase the likelihood of the ointment or gel to cure within the matrix of the backing; and/or will typically prevent, decrease, or increase the likelihood of the ointment or gel to partially penetrate the matrix of the backing.
As used herein, a "topical acne drug" is a compound or combination of compounds that effectively prevents and/or treats acne or a pimple. Any suitable topical acne drug 15 can be employed, provided the topical acne drug 15 effectively treats and/or prevents acne or a pimple and the topical acne drug 15 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the patch 1. Suitable topical acne drugs are disclosed, e.g., in Physician's Desk
Reference (PDR), Medical Economics Company (Montvale, NJ), (53rd Ed.), 1999; Mayo Medical Center Formulary, Unabridged Version, Mayo Clinic (Rochester, MN), January 1998; Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, (11th Ed.), Merck & Co., Inc. (Rahway, NJ), 1989; and references cited therein. Suitable topical acne drugs 15 include, e.g., salicylic acid, resorcinol, resorcinol acetate, calcipotriene, benzoyl peroxide, sulfur, retinol, retinoic acid, citric acid, an alpha hydroxy acid, retinal, pharmaceutically acceptable salts thereof, and combinations thereof. Preferably, the topical acne drug 15 is salicylic acid, or a pharmaceutically acceptable salt thereof. As used herein, "retinoid" refers to vitamin A or vitamin A-like compounds, including, but not limited to, retinoic acid (RA), a natural acidic derivative of vitamin A. Retinoids play a critical role in normal development, growth and differentiation by modulating the expression of target genes.
As used herein, "anthralin" refers to an anthraquinone (the 9, 10 quinone derivative of anthracene; anthraquinones can be made synthetically and also occur in naturally in aloe, cascara sagrada, senna, and rhubarb; the antineoplastic mitoxantrone is a synthetic derivative) derivative that reduces DNA synthesis and mitotic activity in hyperplastic epidermis, restoring the normal rate of
epidermal cell proliferation and keratinization; used topically in the treatment of psoriasis and other skin conditions (also called dithranol).
As used herein, "coal tar" refers to a viscous black liquid containing numerous organic compounds that is obtained by the destructive distillation of coal. Coal tar can be distilled into many fractions to yield a number of useful organic products, including benzene, toluene, xylene, naphthalene, anthracene, and phenanthrene. These substances, called the coal-tar crudes, form the starting point for the synthesis of numerous products — notably dyes, drugs, explosives, flavorings, perfumes, preservatives, synthetic resins, and paints and stains. Coal tar is used medically to treat eczema, psoriasis, seborrheic dermatitis, and other skin disorders.
As used herein, "salicylic acid" refers to 2-hydroxybenzoic acid (C6H4(OH)CO2H), which is a colorless, crystalline organic carboxylic acid. Salicylic acid is used to treat many skin disorders, such as acne, dandruff, psoriasis, seborrheic dermatitis of the skin and scalp, calluses, corns, common warts, and plantar warts.
As used herein, "photochemotherapy with ultraviolet A (PUVA)" refers to a type of ultraviolet radiation treatment (phototherapy) used for severe skin diseases. PUVA is a combination treatment which consists of Psoralen (P) administration and then exposure of the skin to long wave ultraviolet radiation (UVA). Psoralens include compounds which make the skin temporarily sensitive to UVA.
As used herein, "phototherapy with UVB" refers to a type of radiation treatment or therapy involving exposure to ultraviolet B light (wavelength 280- 315 nm).
As used herein, "synergize" or "synergizes" or "synergistic" refers to the working together of two substances to produce an effect greater than the sum of their individual effects (www.webster-dictionary.org/definition/synergize.).
As used herein, "potentiate" or "potentiates" refers to the ability of one substance to make another substance (e.g., of one drug to make a second drug) effective or active or more effective or more active (http://www.ndif.org/Terms/potentiate.html).
As used herein, "alleviate" refers to a physical or mental lightening, lessening, eliminating or diminishing of the severity or length of time of a condition or symptom underlying the condition.
As used herein, "calcipotriene" refers to a synthetic topical form of vitamin D. It is involved in the growth and development of skin cells. Topical calcipotriene is used to treat plaque psoriasis (psoriasis with scaly patches). Chemically, calcipotriene is (5Z,7E, 22E,24S)-24-cyclopropyl-9,10-secochola- 5,7,10(19), 22-tetraene-l alpha, 3 beta, 24-triol-, with the empirical formula C27H40O3. "Therapeutically effective amount" is intended to include an amount of, e.g., xanthophylls useful in the present invention, or an amount of a topical acne drug useful in the present invention, or an amount of the combination of compounds (e.g., xanthophylls and topical acne drug), e.g., to treat the acne or to treat the symptoms of the acne in a host. The combination of compounds is preferably a synergistic combination.
Synergy, as described for example by Chou and Talalay, Adv. Enzyme Regul., 22:27 (1984), occurs when the effect (e.g., treatment of skin disorder) of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at suboptimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased activity, or some other beneficial effect of the combination compared with the individual components.
As used herein, "acne" refers to an inflammatory follicular, papular, or pustular eruption involving the sebaceous apparatus. Acne is a disease of the skin where sebaceous glands are numerous (e.g., face, upper back, and chest) and characteristic lesions are present, e.g., open (blackhead) comedo, closed (whitehead) comedo, papule, pustule, or nodule. It is believed that acne results from the thickening of the follicular opening, increased sebum production, the presence of bacteria, or the host's inflammatory response. The types of acne include, e.g., acne conglobata, chloracne, and rosacea. See, e.g., Stedman's Medical Dictionary, 25th Ed., illustrated, Williams & Wilkins, Baltimore, MD, pp. 15-16 (1990) and Mosby's Medical, Nursing, & Allied Health Dictionary, (5th Ed.), Mosby: St. Louis, p.19 (1998).
As used herein, a "pimple" refers to a small papule, pustule, or furnacle. See, e.g., Mosby's Medical, Nursing, & Allied Health Dictionary, (5th Ed.), Mosby: St. Louis, p.1267 (1998).
As used herein, "fatty acids" refers to organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids can be saturated, unsaturated, or partially unsaturated.
As used herein, "alfalfa" refers to lucern (Medicago sativά).
As used herein, "alpha carotene" refers to a compound of the formula:
As used herein, "beta carotene" refers to a compound of the formula:
Beta-carotene is a proform (prodrug) of vitamin A, and is a lipid-soluble orange pigment found in many vegetables. Beta-carotene is converted to vitamin A in the body with an efficiency of approximately 50 percent.
As used herein, "vitamin A" refers to a compound of the formula:
which is chemically designated as 3,7-dimethyl-9-(2,6,6-trimethyl-l- cyclohexen-l-yl)-2,4,6,8-nonatetraen-l-ol.
As used herein, "cancer" includes a type of disease caused by cells that divide and grow uncontrollably, invading and disrupting other tissues and spreading to other areas of the body (metastasis). It is an abnormal uncontrolled growth of tissue that has potential to spread to distant sites of the body. Cancer exerts its deleterious effect on the body by: (a) Destroying the surrounding adjacent tissues: e.g. compressing nerves, eroding blood vessels, or causing perforation of organs; and (b) Replacing normal functioning cells in distant sites: e.g. replacing blood forming cells in the bone marrow, replacing bones leading to increased calcium levels in the blood, or in the heart muscles so that the heart fails.
As used herein, "ulcer" includes a sore, often deep, sometimes inflamed, which heals slowly or not at all. As used herein, "macular degeneration" includes the breakdown or damage to a portion of the retina known as the macula. Symptoms include blurring of vision (in central visual field), colors appear dim and difficulty reading or performing work up close.
Alpha-lipoic acid provides superior antioxidant protection due to the fact that it enhances the potency of other antioxidants in the body. Alpha-lipoic acid may be added to the formulation 5 of the present invention if desired, in any suitable and appropriate amount.
Phenolic compounds such oligomeric proanthocyanidins are additional useful antioxidants. Oligomeric proanthocyanidins are found naturally in grape seeds. Phenolic compounds may be added to the composition of the present invention if desired.
Antibiotic
The formulation 5 can further include an antibiotic. As used herein, an "antibiotic" is any compound having activity against either Gram-positive or Gram-negative organisms (i.e., inhibits the growth or destroys the development of either Gram-positive or Gram-negative organisms). Stedman's Medical Dictionary, Illustrated. (25th Ed.), Williams & Wilkins: Baltimore (1990) and
Mosbv's Medical, Nursing, & Allied Health Dictionary, (5th Ed.), Mosby: St. Louis (1998).
Suitable antibiotics are disclosed, e.g., in Physician's Desk Reference (PDR), Medical Economics Company (Montvale, NJ), (53rd Ed.), 1999; Mayo Medical Center Formulary, Unabridged Version, Mayo Clinic (Rochester, MN), January 1998; Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals. (11th Ed.), Merck & Co., Inc. (Rahway, NJ), 1989; University of Wisconsin Antimicrobial Use Guide, http://www.medsch.wisc.edu/clinsci/ amcg/amcg.html; Introduction on the Use of the Antibiotics Guideline, Descriptions of Specific Antibiotic Classes, Thomas Jefferson University, http://jeffiine.tju.edu/CWIS/OAC/antibiotics_guide/intro.html; and references cited therein.
Suitable antibiotics include, e.g., aminoglycosides, /3-lactam antibiotics, cephalosporins, macrolides, miscellaneous antibiotics, penicillins, tetracyclines, antifungals, antimalarial agents, antituberculosis agents, antivirals, leprostatics, miscellaneous anti-infectives, quinolones, sulfonamides, urinary anti-infectives, nasal antibiotics, opthalmic antibiotics, opthalmic antivirals, opthalmic quinalones, opthalmic sulfonamides, skin and mucous membrane antibiotics, skin and mucous membrane antifungals, skin and mucous membrane antivirals, skin and mucous membrane miscellaneous anti-infectives, skin and mucous membrane scabicides and pedulicides, skin and mucous membrane antinepolasts, nitrofurans, and oxazolidinones. Physician's Desk Refernce (PDRl Medical Economics Company (Montvale, NJ), (53rd Ed.), 1999 and Mayo Medical Center Formulary, Unabridged Version, Mayo Clinic (Rochester, MN), January 1998.
Aminoglycosides include, e.g., Amikacin (amikacin sulfate); Garamycin (gentamicin sulfate); Nebcin (tobramycin sulfate); Netromycin (netilmicin sulfate); Streptomycin Sulfate; and TOBI (tobramycin). jS-Lactam antibiotics include, e.g., Azactam (aztreonam); Cefotan (cefotetan); Lorabid (loracarbef); Mefoxin (cefoxitin); Merrem (meropenem); and Primaxin (imipenem and cilastatin for injectable suspension).
Cephalosporins include, e.g., Ancef (cefazolin); Ceclor (cefaclor); Cedax (ceftibuten); Cefizox (ceftizoxime sodium); Cefobid (cefoperazone sodium); Ceftin (cefuroxime axetil); Cefzil (cefprozil); Ceptaz (ceftazidime); Claforan
(cefotaxime); Duricef (cefadroxil monohydrate); Fortaz (ceftazidime); Keflex (cephalexin); Keftab (cephalexin HCl); Kefurox (cefuroxime); Kefzol (cefazolin); Mandol (cefamandole nafate); Maxipime (cefepime HCl); Monocid (cefonicid sodium); Omnicef (cefdinir); Rocephin (ceftriaxone); Suprax (cefixime); Tazicef (ceftazidime); Tazidime (ceftazidime); Vantin (cefpodoxime proxetil); and Zinacef (cefuroxime).
Macrolides include, e.g., Biaxin (clarithromycin); Dynabac (dirithromycin); E.E.S. 200 (Erythromycin Ethylsuccinate); E.E.S. 400 (Erythromycin Ethylsuccinate); Ery-Ped 200 (Erythromycin Ethylsuccinate); EryPed 400 (Erythromycin Ethylsuccinate); Ery-Tab (Erythromycin delayed- release tablets); Erythrocin Stearate (Erythromycin stearate); Ilosone (erythromycin estolate); PCE Dispertab (erythromycin particles in tablets); Pediazole (erythromycin ethylsuccinate and sulfϊsoxazole acetyl for oral suspension); Tao (troleandomycin); Zithromax (azithromycin); and Erythromycin.
Miscellaneous antibiotics include, e.g., Cleocin HCl (clindamycin hydrochloride); Cleocin Phosphate (clindamycin phosphate); Coly-Mycin M (colistimethate sodium); and Vancocin HCl (vancomycin hydrochloride). Penicillins include, e.g., Amoxil (amoxicillin); Augmentin (amoxicillin/clavulanate potassium); Bicillin C-R 900/300 (Penicillin G benzathine and Penicillin G procaine suspension); Bicillin C-R (Penicillin G benzathine and Penicillin G procaine suspension); Bicillin L-A (Penicillin G benzathine suspension); Geocillin (carbencillin indanyl sodium); Mezlin (sterile mezlocillin sodium); Omnipen (ampicillin); Pen-Vee K (penicillin V potassium); Pfizerpen (penicillin G potassium); Pipracil (piperacillin sodium); Spectrobid (bacampicillin HCl); Ticar (ticarcillin disodium); Timentin (ticarcillin disodium and clavulanate potassium); Unasyn (ampicillin sodium/sulbactam sodium); Zosyn (piperacillin sodium and tazobactam sodium); and Dicloxacillin Sodium. Tetracyclines include, e.g., Achromycin V (tetracycline HCl); Declomycin (demeclocycline HCl); Dynacin (minocylcine HCl); Minocin
(minocycline hydrochloride); Monodox (Doxycycline monohydrate capsules); Terramycin (oxytetracyline); Vectrin (minocycline hydrochloride); Vibramycin Calcium (doxycycline sodium); Vibramycin Hyclate (doxycycline hyclate); Vibramycin Monohydrate (doxycycline monohydrate); Vibra-Tabs (doxycycline
hydrate); Declomycin (demeclocycline HCl); Vibrarnycin (doxycycline); Dynacin (Minocyline HCl); Terramycin (oxytetracycline HCl); Achromycin V capsules (tetracycline HCl); Lincomycins; and Cleocin HCl (clindamycin HCl).
Antifungals include, e.g., Abelcet (amphotericin B lipid complex); AmBisome (amphotericin B); Amphotec (amphotericin B cholesterol sulfate complex); Ancobon (flucytosine); Diflucan (fluconazole); Fulvicin P/G (ultramicrosize griseofulvin); Fulvicin P/G 165 and 330 (ultramicrosize griseofulvin); Grifulvin V (griseofulvin); Gris-PEG (griseofulvin ultramicrosize); Lamisil (terbinafine hydrochloride); Nizoral (ketoconazole); Amphotericin B; Lotrimin (clotrimazole); Dapsone tablets (dapsone); Diflucan (fluconazole); Monistat-Derm cream (miconazole); Mycostatin Cream (nystatin); and Sporanox (itraconazole).
Antimalarial agents include, e.g., Aralen hydrochloride (chloroquine HCl); Aralen phosphate (chloroquine phosphate); Daraprim (pyrimethamine); Lariam (mefloquine HCl); and Plaquenil (hydroxychloroquine sulfate).
Antituberculosis agents include, e.g., Capastat sulfate (capreomycin sulfate); Myambutol (ethambutol hydrochloride); Mycobutin (rifabutin capsules); Nydrazid (isoniazid injection); Paser (aminosalicylic acid); Priftin (rifapentine); Pyrazinamide tablets (pyrazinamide); Rifadin (rifampin capsules); Rifadin IV (rifampin for injection); Rifamate (rifampin and isoniazid); Rifater (rifampin, isoniazid and pyrazinamide); Seromycin (cycloserine capsules); Streptomycin Sulfate; Tice BCG (BCG vaccine); Cycloserine (seromycin capsules); Urised (Mefhenamine); and Trecator-SC (ethionamide tablets). Antivirals include, e.g., Alferon N (interferon alfa-n3); Crixivan (indinavir sulfate); Cytovene (ganciclovir); Cytovene-IV (ganciclovir sodium); Epivir (lamivudine); Famvir (famciclovir); Flumadine (rimantadine HCl); Foscavir (foscarnet sodium); Hivid (zalcitabine); Intron A (interferon alfa-2b); Invirase (saquinavir mesylate); Norvir (ritonavir); Rebetron combination therapy, which contains Rebetrol (ribavirin) and Intron A (inteferon alfa-2b); Rescriptor (delavirdine mesylate); Retrovir (ziduvudine); Retrovir IV
(zidovudine); Symmetrel (amantadine hydrochloride); Synagis (palivizumab); Valtrex (valacyclovir HCl); Videx (didanosine); Viracept (nelfmavir mesylate); Viramune (nevirapine); Virazole (ribavirin); Vistide (cidofovir); Zerit (stavudine
(d4T)); Symmetrel Syrup (amantadine HCl); Combivir Tablets (lamiduvine); and Zovirax (acyclovir).
Leprostatics include, e.g., Dapsone Tablets (dapsone).
Miscellaneous anti-infectives include, e.g., Daraprim (pyrimethamine); Flagyl 375 (metronidazole); Flagyl ER Tablets (metronidazole); Flagyl IV.
(metronidazole); Furoxone (furazolidone); Mepron (atovaquone); andNeutrexin (trimetrexate glucuronate).
Quinolones include, e.g., Cipro (ciprofloxacin HCl); Floxin (ofloxacin); Levaquin (levofloxacin); Mazaquin (lomefloxacin HCl); Noroxin (norfloxacin); Penetrex (enoxacin); Raxar (grepafloxacin HCl); Trovan (trovafloxacin mesylate); and Zagam (sparfloxacin).
Sulfonamides include, e.g., Bactrim (trimethoprim and sulfamethoxazole); Bactrim DS (trimethoprim and sulfamethoxazole double strength); Pediazole (erythromycin ethylsuccinate and sulfisaxazole acetyl); Septra (trimethoprim and sulfamethoxazole); Septra DS (trimethoprim and sulfamethoxazole); Co-Trimoxazole, Sulfadiazine, Bactrim LV. Infusion (sulfamethoxazole); Sulfapyridine, and Pediazole (erythromycin ethylsuccinate and sulfisoxazole acetyl).
Urinary anti-infectives include, e.g., Furadantin (nitrofurantoin); Macrobid (nitrofurantoin monohydrate macrocrystals); Macrodantin
(nitrofurantoin macrocrystals); Monurol Sachet (fosfomycin tromethamine); NegGram Caplets (nalidixic acid); Septra (trimethoprim and sulfamethoxazole); Septra DS (trimethoprim and sulfamethoxazole); Urised (a combination of the antiseptics methenamine, methylene blue, phenyl salicylate, benzoic acid and parasympatholytics (atropine sulfate) hyoscyamine); Urobiotic-250 Capsules (oxytetracycline HCl, sulfamethizole and phenazopyridine HCl); and Uroqid Acid No. 2 Tablets (methenamine mandelate).
Nasal antibiotics include, e.g., Bactroban (mupirocin).
Opthalmic antibiotics include, e.g., Chloromycetin opthalmic (chloramphenical); Cortisporin (neomycin and polymyxin β sulfates and hydrocortisone acetate cream); Ilotycin (erythromycin opthalmic ointment); NeoDecadron (neomycin sulfate - dexamethasone sodium phosphate); Polytrim (trimethoprim and polymyxin β sulfate opthalmic solution); Terra-Cortril (oxytetracycline HCl and hydrocortisone acetate); Terramycin (oxytetracycline);
and TobraDex (tobramycin and dexamethasone opthalmic suspension and ointment).
Opthalmic antivirals include, e.g., Vira-A opthalmic ointment, (vidarabine). Opthalmic quinalones include, e.g., Chibroxin (norfloxacin opthalmic solution); Ciloxan opthalmic solution, (Ciprofloxacin HCl); Ciloxan opthalmic ointment, (Ciprofloxacin HCl); and Ocuflox opthalmic solution (ofloxacin).
Opthalmic sulfonamides include, e.g., Blephamide opthalmic ointment (sulfacetamide sodium and prednisolone acetate); and Blephamide opthalmic suspension (sulfacetamide sodium and prednisolone acetate).
Skin and mucous membrane antibiotics include, e.g., A/T/S (erythromycin); Bactroban (mupirocin); Benzamycin (erythromycin-benzoyl peroxide topical gel); Betadine (povidone-iodine); Cleocin T (clindamycin phosphate topical solution); Clindets (clindamycin phosphate pledgets); Cortisporin (neomycin, polymyxin B sulfates and hydrocortisone acetate cream); Emgel (erythromycin); Erycette (erythromycin topical solution); Garamycin (gentamicin sulfate); Klaron (sodium sulfacetamide lotion); Mycostatin (nystatin cream); Theramycin Z (erythromycin topical solution); T-Stat (erythromycin); Chloromycetin (chloramphenicol opthalmic ointment); Cortisporin (neomycin and polymyxin B sulfates, bacitracin zinc and hydrocortisone opthalmic ointment); Ilotycin (erythromycin); NeoDecadron (neomycin sulfate- dexamethasone sodium phosphate); Polytrim (trimethoprim and polymyxin B sulfate); Terra-Cortril (oxytetracycline HCl and hydrocortisone acetate); Terramycin (oxytetracycline); and TobraDex (tobramycin and dexamethasone opthalmic suspension and ointment).
Skin and mucous membrane antifungals include, e.g., Exelderm (sulconazole nitrate); Fungizone (amphotericin B oral suspension); Lamisil (terbinafme hydrochloride cream); Loprox (ciclopiroxolamine); Lotrimin (clotrimazole); Lotrisone (clotrimazole and betamethasone diproprionate); Mentax (butenafme HCl); Monistat-Derm (miconazole nitrate); Mycelex (clotrimazole); Mycostatin (nystatin); Naftin (naftifme HCl); Nizoral (ketoconazole); Nystop (nystatin); Oxistat (oxiconazole nitrate); Selsun Rx (2.5% selenium sulfide lotion); and Spectazole (econazole nitrate).
Skin and mucous membrane antivirals include, e.g., Denavir (penciclovir cream); and Zovirax (acyclovir).
Skin and mucous membrane miscellaneous anti-infectives include, e.g., Benzashave (benzoyl peroxide); Betadine (povidone-iodine); Betasept (chlorhexidine gluconate); Cetaphil (soap substitute); Clorpactin WCS-90 (sodium oxychlorosene); Dapsone Tablets (dapsone); Desquam-E (benzoyl peroxide); Desquam-X (benzoyl peroxide); Hibiclens (chlorhexidine gluconate); Hibistat (chlorhexidine gluconate); Impregon (tetrachlorosalicylanilide 2%); MetroCream (metronidazole); MetroGel (metronidazole); Noritate (metronidazole); pHisoHex (hexachlorophene detergent cleanser); Sulfacet-R (sodium sulfacetamide 10% and sulfur 5%); Sulfamylon (matenide acetate); Triaz (benzoyl peroxide); and Vanoxide-HC (benzoyl peroxide hydrocortisone).
Skin and mucous membrane scabicides and pedulicides include, e.g., Acticin (permethrin); Elimite (permethrin); Eurax (crotamiton); and Lindane Lotion USP 1 % (lindane) .
Skin and mucous membrane antinepolasts include, e.g., Efudex (fluorouracil); and Fluoroplex (fluorouracil).
Nitrofurans include, e.g., Furadantin Oral Suspension (nitrofurantoin).
Oxazolidinones include, e.g., Zyvox (linezolid). It is appreciated that those skilled in the art understand that the antibiotic useful in the present invention is the biologically active compound present in any of the antibiotic formulations disclosed above. For example, Azactam (aztreonam) is typically available as an injectable solution. The antibiotic, however, is (z)-2-[[[(2-amino-4-thiazolyl) [[(2S,-3S)-2-methyl-4-oxo-l-sulfo-3- azetidinyl] carbamoyl] methylene] amino] oxy]-2-methyl propionic acid.
Physician's Desk Reference (PDR), Medical Economics Company (Montvale, NJ), (53rd Ed.), pp. 820-823, 1999.
Amikacin (amikacin sulfate) is commercially available from Elkins-Sinn and is D-Streptamine, O-3-amino-3-deoxy-α-D-glucopyranosyl-(l-»6)-O-6- deoxy-α-D-glucopyranosyl-(l-^4)]-N'-(4-amino-2 hydroxy-l-oxobutyl)-2- deoxy-, (S)-, sulfate (1:2) (salt).
Garamycin (gentamicin sulfate) is commercially available from Schering.
Nebcin (tobramycin sulfate) is commercially available from Lilly and is 0-3-amino-3-deoxy-O!-D-glucopyranosyl-(l-^4)-O-[2,6-diamino-2,3-6-trideoxy- o:-D-rz&o-hexopyranosyl-(l — > 6)]-2-deoxy-L-streptamine, sulfate (2:5) (salt).
Netromycin (netilmicin sulfate) is commercially available from Schering and is O-3-Deoxy-4-C-methyl-3-(methylamino)-/3-L-ara-binopyranosyl (1→4)- O-[2,6-diamino-2,3,4,6-tetradeoxy-α;-D-g/>'cero-liex-4-enopyranosyl-(l→'6)-2- deoxy-N3-ethyl-L-streptamine sulfate (2:5) salt.
Streptomycin Sulfate is commercially available from Pfizer and is D- Streptamine, O-2-deoxy-2-(methyl amino)-α-L-glucopyranosyl-(l -»2)-O-5- deoxy-3-C-formyl-α-L-lyxofuranosyl, (l→4)-N,N'-bis(ammoiminomethyl)-, sulfate (2:3) (salt).
TOBI (tobramycin) is commercially available from Pathogenesis Corporation and is O-3-amino-3-deoxy-Q!-D-glucopyranosyl-(l-^4)-O-[2,6- diamino-2,3,6-trideoxy-α-D-πδo-hexopyranosyl-(l->6)]-2-deoxy-L- streptamine.
Azactam (aztreonam) is commercially available from Bristol-Myers Squibb and is (Z)-2-[[[(2-amino-4-thiazolyl) [[(2S,-3S)-2-methyl-4-oxo-l-sulfo- 3-azetidinyl] carbamoyl] methylene] amino] oxy]-2-methylpropionic acid.
Cefotan (cefotetan) is commercially available from Zeneca and is the disodium salt of [6R-(6α, 7α)]-7-[[[4-(2-amino-l-carboxy-2-oxoethylidene)-l-3, dithietan-2-yl] carbonyl] amino] -7-methoxy-3-[ [(I -methyl-lH-tetrazol-5-yl) thio] methylJ-δ-oxo-S-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid.
Lorabid (loracarbef) is commercially available from Lilly and is (6R, 7S)-7-[(R)-2-amino-2-phenylacetamido]-3-chloro-8-oxo-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, monohydrate.
Mefoxin (cefoxitin) is commercially available from Merck and is sodium (6R, 7S)-3-(hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl) acetamido]-5- thia-1-azabicylo [4.2.0] oct-2-ene-2-carboxylate carbamate (ester).
Merrem (meropenem) is commercially available from Zeneca and is (4R, 5S, 6S)-3-[(3S, 5S)-5-(Dimethylcarbamoyl)-3-pyrrolidinyl] thiol]-6-[(lR)-l- hydroxyethyl]-4-methyl-7-oxo-l-azabicyclo [3.2.0] hept-2-ene-2-carboxylic acid trihydrate.
Primaxin (imipenem and cilastatin for injectable suspension) is commercially available from Merck and is (1) imipenem is N- formimidoylthienamycin monohydrate, chemical name is [5R-[5α, 6α (R*)]]-6- (l-hydroxyethyl)-3-[[2-[(iminomethyl) amino] ethyl] thio]-7-oxo-l-azabicylco [3.2.0] hept-2-ene-2-carboxylic acid monohydrate, cilastatin sodium is [R-[R*, S*,-(Z)]]-7-[(2-amino-2-carboxyethyl) thio]-2-[[(2, 2-dimethyl cyclopropyl) carbonyl] amino] -2-heptenoic acid, monosodium salt.
Ancef (cefazolin) is commercially available from SmithKline Beecham and is 3-{[(5-methyl-l,3,4-thiadiazol-2-yl) thio-methyl]}-8-oxo-7-[2-(lH- tetrazol-1-yl) acetamido]-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid.
Ceclor (cefaclor) is commercially available from Lilly and is 3-chloro-7- D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid monohydrate; Cedax (ceftibuten) is commercially available from Schering and is (+)-(6R, 7R)-7-[(Z)- 2-(2-(2-amino-4-thiazoly)-4-carboxycrotonamido]-8-oxo-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, dihydrate.
Cefizox (ceftizoxime sodium) is commercially available from Fujisawa and is sodium salt of [6R-[6α, 7/3 (Z)]]-7 [[2, 3, dihydro-2-imino-4- thiazolyl)(methoxy amino) acetyl] amino]-8-oxo-5-thia-l-azabicyclo [4.2.0] oct- 2-ene-2-carboxyolic acid.
Cefobid (cefoperazone sodium) is commercially available from Pfizer and is sodium (6R, 7R)-7 [(R)-2-(4-ethyl-2, 3, dioxo-1-piperazine carboxamido)- 2-(p-hydroxyphenyl)-acetamido)-3-[[(l-methyl-lH-tetrazol-5-yl) thio] methyl]- 8-oxo-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylate. Ceftin (cefuroxime axetil) is commercially available from Glaxo
Wellcome and is (RS)-l-hydroxyethyl (6R, 7R)-7-[2-(2-furyl) glyoxylamido]-3- (hydroxyethyl)-(8-oxo-5-thia-l-aza-bicyclo [4.2.0] oct~2-ene-2-carboxylate, 72 (Z)-O-methyl-oxime), 1-acetate 3-carbamate.
Cefzil (cefprozil) is commercially available from Bristol-Myers Squibb and is (6R, 7R)-7-[(R)-2-amino-2-(p-hydroxyphenyl) acetamido]-8-oxo-3- propenyl-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid monohydrate. Ceptaz (ceftazidime) is commercially available from Glaxo Wellcome and is l-[[7-[[(2-amino-4-thiazolyl) [(1-carboxy-l-methylethoxy) imine] acetyl]
aminol-l-carboxy-δ-oxo-S-thia-l-azabicyclo [4.2.0] oct-2-en-3-yl] methyl]-, hydroxide, inner salt, [6R-[6α, 7/3 (Z)]].
Claforan (cefotaxime) is commercially available from Hoescht Marion Roussel and is 7-[2-(2-amino-4-thiazolyl) glyoxylamido]-3-(hydroxy methyl)-8- oxo-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylate 72 (Z)-(O- methyloxime), acetate (ester).
Duricef (cefadroxil monohydrate) is commercially available from Bristol-Myers Squibb and is 5-Thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7-[[amino (4-hydroxyphenyl) acetyl] amino]-3-methyl-8-oxo,- monohydrate, [6R-[6α, 7/3 (R*)]]-.
Fortaz (ceftazidime) is commercially available from Glaxo Wellcome and is l-[[7-[[(2-amino-4-thiazolyl) [1-carboxy-l-methylethoxy) imino] acetyl] amino]-2-carboxy-8-oxo-5-thia-l-azabicyclo [4.2.0] oct-2-en-3-yl] methyl]-, hydroxide, inner salt [6R-[6α, 7/3 (Z)]]. Keflex (cephalexin) is commercially available from Dista and is 7-(D-α-
Amino-α-phenyl acetamido)-3-methyl-3-cephem-4-carboxylic acid monohydrate.
Keftab (cephalexin HCl) is commercially available from Dura and is 7- (D-2-Amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid hydrochloride monohydrate.
Kefurox (cefuroxime) is commercially available from Lilly and is the sodium salt of (6R.7R) 3-carbamoyloxymethyl-7-[Z-2-methoxyimino-2-(fur-2- yl) acetamiodo] ceph-3-em-4-carboxylate.
Kefzol (cefazolin) is commercially available from Lilly and is the sodium salt of 3-{[(5-methyl-l,3,4-thiadiazol-2-yl) thio] methyl} -8-oxo-7-[2-(lH- tetrazol-1-yl) acetamido]-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-caboxylic acid.
Mandol (cefamandole nafate) is commercially available from Lilly and is 5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7-[[(formyloxy) phenyl acetyl] amino]-3-[[(l-methyl-lH-tetrazol-5-yl) thio] methyl] -8-oxo-, mono- sodium salt, [6R-[6α-7/3 (R*)]].
Maxipime (cefepime HCl) is commercially available from Bristol-Myers Squibb and is 1-[[6R, 7R)-7-[2-amino-4-thiazolyl)-glyoxylamido]-2-carboxy-8- oxo-5-thia-l-azabicyclo-[4.2.0]oct-2-en-3-yl] methyl]-l-methylpyrrolidinium chloride, 72-(Z)-(O-methyloxime), monohydrochloride, monohyrate.
Monocid (cefonicid sodium) is commercially available from SmithKline Beecham and is 5-Thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7- [(hydroxyphenyl-acety^-aminol-S-oxo-S-ttl-Csulfomethy^-lH-tetrazol-S-yl] thio] methyl]-disodium salt, [6R-[6α, 7/3 (R*)]]. Omnicef (cefdinir) is commercially available from Parke Davis and is
[6R-[6α, 7/3 (Z)]]-7-[[(2-amino-4-thiazolyl)-(hydroxyimino) acetyl] amino]-3- ethenyl-8-oxo-5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid.
Rocephin (ceftriaxone) is commercially available from Roche Laboratories and is (6R, 7R)-7-[2-(2-Amino-4-thiazolyl) glyoxylamido]-8-oxo- 3-[[(l ,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as-triazin-3-yl) thio] methyl]-5-thia- 1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 72-(Z)-O-methyloxime), disodium salt, sesquaterhydrate.
Suprax (cefixime) is commercially available from Lederle Laboratories and is (6R, 7R)-7-[2-(2-Amino-4-thiazolyl) glyoxylamido]-8-oxo-3-vinyl-5-thia- 1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 72-(Z)-[O-(carboxymethyl) oxime] trihydrate.
Tazicef (ceftazidime) is commercially available from SmithKline Beecham and is pentahydrate of Pyridinium, l-[[7-[[2-amino-4-thiazolyl) [(1- carboxy-1-methylethoxy) imino] acetyl] ammo]-2-carboxy-8-oxo-5-thia-l- azabicyclo (4.2.0) oct-2-en-3-yl] methyl] -hydroxide, inner salt, [6R, -[6a, 7/3
(Z)]].
Tazidime (ceftazidime) is commercially available from Lilly and is pentahydrate of Pyridinium, l-[[7-[[2-amino-4-thiazolyl) [(1-carboxy-l- methylethoxy) imino] acetyl] amino]-2-corboxy-8-oxo-5-thia-l-azabicyclo (4.2.0) oct-2-en-3-yl] methyl] -hydroxide, inner salt, [6R, -[6a, Iβ (Z)]].
Vantin (ceφodoxime proxetil) is commercially available from Pharmacia & Upjohn and is (RS)-I (isopropoxycarbonyloxy) ethyl (+)-(6R, 7R)-7-[2-(2- amino-4-thiazolyl)-2-{(Z)methoxyimino} acetamido]-3-methoxymethyl-8-oxo- 5-thia-l-azabicyclo [4.2.0] oct-2-ene-2-carboxylate. Zinacef (cefuroxime) is commercially available from Glaxo Wellcome and is sodium salt of (6R, 7R)-3-carbamoyloxymethyl-7-[Z-2-methoxy-imino-2- fur-2-yl) acetamido] ceph-3-em-4-carboxylate.
Biaxin (clarithromycin) is commercially available from Abbott and is 6- O-methylerythromycin.
Dynabac (dirithromycin) is commercially available from Sanofi and is (9S)-9-Deox-l l-deoxy-9, 1 l-[imino [(7i?)-2-(2-methoxyethoxy)-ethylidene] oxy] erythromycin.
E.E.S. 200 (Erythromycin Ethylsuccinate) is commercially available from Abbott and is erythromycin 2'-(ethylsuccinate).
E.E.S. 400 (Erythromycin Ethylsuccinate) is commercially available from Abbott and is erythromycin 2'-(ethylsuccinate).
Ery-Ped 200 (Erythromycin Ethylsuccinate) is commercially available from Abbott and is erythromycin 2'-(ethylsuccinate). EryPed 400 (Erythromycin Ethylsuccinate) is commercially available from Abbott and is erythromycin 2'-(ethylsuccinate).
Ery-Tab (Erythromycin delayed-release tablets) is commercially available from Abbott and is (3R*. 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-Q!-L-πέo-hexopyranosyl) oxy]- 14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy- 3-(dimethylamino)-|8-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
Erythrocin Stearate (Erythromycin stearate) is commercially available from Abbott and is the stearate salt of (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-α-L-π6o- hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3-(dimethylamino)-|8-D-x);/c»-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10-dione.
Ilosone (erythromycin estolate) is commercially available from Dista and is erythromycin 2'-propionate, dodecyl sulfate.
PCE Dispertab (erythromycin particles in tablets) is commercially available from Abbott and is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-0-methyl-α-L-π6o-hexopyranosyl) oxy]- 14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy- 3-(dimethylamino)-/3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
Pediazole (erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension) is commercially available from Ross Products and is T-
ethylsuccinyl ester of erythromycin (erythromycin ethylsuccinate) and N-(3, 4- dimethyl-5-isoxazolyl)-N-sulfanilylacetamide (sulfisoxazole acetyl).
Tao (troleandomycin) is commercially available from Pfizer and is the synthetically derived acetylated ester of oleandomycin. Zithromax (azithromycin) is commercially available from Pfizer and is
{2R, 3S, AR, 5R, SR, 1OR, UR, US, 138, 14i?)-13-[(2, 6-dideoxy-3-C-methyl-3- O-methyl-α-L-πόo-hexopyranosyl) oxy]-2-ethyl-3, 4, 10-trihydroxy-3, 5, 6, 8, 10, 12, 14-heptamethyl-l l-[[3, 4, 6-1aMeoxy-3-(dimethylamino)-/3-/J>-;cy/ø- hexopyranosyl] oxyJ-l-oxa-ό-azacyclopentadecan-lS-one. Erythromycin, which is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, 1 IR*, 12R*,
13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-0-methyl-θ!-L-rzδo-hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6- trideoxy-3-(dimethylamino)-/3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10-dione. Cleocin HCl (clindamycin hydrochloride) is commercially available from
Pharmacia & Upjohn and is the hydrated hydrochloride salt of clindamycin, a semisynthetic antibiotic produced by a 7 (S)-chlorosubstitution of the (7R) hydroxyl group of lincomycin.
Cleocin Phosphate (clindamycin phosphate) is commercially available from Pharmacia & Upjohn and is L-tAreø-α-D-gα/αcto-Octopyranoside, methyl 7 chloro-6, 7, 8,-trideoxy-6-[[(l-methyl-4-propyl-2-pyrrolidinyl) carbonyl] amino]-l-thio-, 2-(dihydrogen phosphate), (2S-tran$)-.
Coly-Mycin M (colistimethate sodium) is commercially available from Monarch. Vancocin HCl (vancomycin hydrochloride) is commercially available from Lilly.
Amoxil (amoxicillin) is commercially available from SmithKline Beecham and is (2S, 5R, 6i?)-6-[(i-)-(-)-2-amino-2-(p-hydroxyphenyl) acetamido]-3, 3-dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0]-heptane-2- carboxylic acid trihydrate.
Augmentin (amoxicillin/clavulanate potassium) is commercially available from SmithKline Beecham and is (2S, 5R, 6i?)-6-[(i?)-(-)-2-amino-2-(p- hydroxy phenyl) acetamido]-3, 3-dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0]- heptane-2-carboxylic acid trihydrate (amoxicillin) and potassium (Z)-(2R, 5R)-3-
(2-hydroxyethylidene)-7-oxo-4-oxa-l-azabicyclo [3.2.0]-heptane-2-carboxylate (clavulanate potassium).
Bicillin C-R 900/300 (Penicillin G benzathine and Penicillin G procaine suspension) is commercially available from Wyeth-Ayerst and is (IS, 5R, 6R)-3, 3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heptane-2- carboxylic acid compound with N, N'-dibenzylethylenediamine (2:1), tetrahydrate (Penicillin G benzathine) and (25, 5R, 6R)-3, 3-Dimethyl-7-oxo-6- (2-phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heρtane-2-carboxylic acid compound with 2-(diethylamino) ethyl />-amino benzoate compound (1:1) monohydrate (Penicillin G procaine) .
Bicillin C-R (Penicillin G benzathine and Penicillin G procaine suspension) is commercially available from Wyeth-Ayerst and is (2S, 5R, 6R)-3, 3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heptane-2- carboxylic acid compound with N, N'-dibenzylethylenediamine (2:1), tetrahydrate (Penicillin G benzathine) and (2S, 5R, 6R)-3, 3-Dimethyl-7-oxo-6- (2-phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylic acid compound with 2-(diethylamino) ethyl />-amino benzoate compound (1:1) monohydrate (Penicillin G procaine).
Bicillin L-A (Penicillin G benzathine suspension) is commercially available from Wyeth-Ayerst and is (25, 5R, 6R)-3, 3-Dimethyl-7-oxo-6-(2- phenylacetamido)-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylic acid compound with N, N'-dibenzylethylenediamine (2:1), tetrahydrate.
Geocillin (carbencillin indanyl sodium) is commercially available from Pfizer and is l-(5-Indanyl)-N-(2-carboxy-3-3-dimethyl-7-oxo-4-thia-l- azabicyclo [3.2.0] hept-6-yl)-2-phenylmalonamate monsodium salt.
Mezlin (sterile mezlocillin sodium) is commercially available from Bayer and is the monohydrate sodium salt of 6-{D-2[3[(methyl-sulfonyl)-2-oxo- imidazolidine-l-carboxamido]-2-phenyl acetamido} penicillanic acid.
Omnipen (ampicillin) is commercially available from Wyeth-Ayerst and is (2S, 5R, 6R)-6-[(R)-2-Amino-2-phenylacetamido]-3, 3-dimethyl-7-oxo-4-thia- 1-aza-bicyclo [3.2.0] heptane-2-carboxylic acid.
Pen-Vee K (penicillin V potassium) is commercially available from Wyeth-Ayerst and is the potassium salt of the phenoxymethyl analog of penicillin G.
Pfizerpen (penicillin G potassium) is commercially available from Pfizer and is monopotassium 3, 3-dimethyl-7-oxo-6-(2-phenylacetarnido)-4-thia-l- azabicyclo (3.2.0) heptane-2-carboxylate.
Pipracil (piperacillin sodium) is commercially available from Lederle and is 4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylic acid, 6-[[[[(4-ethyl-2-3- dioxo-1-piperazinyl) carbonyl] amino] phenylacetyl] amino] -3, 3-dimethyl-7- oxo-, monosodium salt, [2S-[2α, 5a, 6β (S*)]].
Spectrobid (bacampicillin HCl) is commercially available from Pfizer and is r-ethoxycarbonyloxyethyl-6-(D-Cϋ aminophenylacetamide)-penicillate hydrochloride.
Ticar (ticarcillin disodium) is commercially available from SmithKline Beecham and is N-(2-carboxy-3, 3-dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0] hept-6-yl)-3-thiophenemalonamic acid disodium salt.
Timentin (ticarcillin disodium and clavulanate potassium) is commercially available from SmithKline Beecham and is N-(2-carboxy-3, 3- dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0] hept-6-yl)-3-thiophenemalonamic acid disodium salt (ticarcillin disodium) and potassium (Z)-(2R, 5R)-3-(2- hydroxyethylidene)-7-oxo-4-oxa-l-azabicyclo [3.2.0] heptane-2-carboxylate (clavulanate potassium). Unasyn (ampicillin sodium/sulbactam sodium) is commercially available from Pfizer and is monosodium (2S, 5R, 6R)-6-[(R)-2-Amino-2-phenyl acetamido]-3, 3-dimethyl-7-oxo-4-thia-l-aza-bicyclo [3.2.0] heptane-2- carboxylate (amipicillin sodium), and sodium penicillate sulfone; sodium (2S, 5R)-3, 3-dimethyl-7-oxo-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylate 4, 4- dioxide (sulbactam sodium).
Zosyn (piperacillin sodium and tazobactam sodium) is commercially available from Lederle and is sodium (2S, 5R, 6i?)-6[(i?)-2-(4-ethyl-2, 3-dioxo-l- piperazine-carboxamido)-2-phenylacetamido] -3, 3 -dimethyl-7-oxo-4-Thia- 1 - azabicylco-[3.2.0] heptane-2-carboxylate (piperacillin sodium), and sodium (2S, 3S, 5R) -3-methyl-7-oxo-3-(l#-l, 2, 3-triazol-l-ylmethyl)-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylate-4, 4-dioxide (tazobactam sodium).
Dicloxacillin Sodium is monosodium (2S,5R,6R)-6-(3-(2,6- dichloroρhenyl)5-methyl-4 -isoxazolecarboxamido]-3,3-dimethyl-7-OXO-4- thia-l-azabicyclo[3.2.0] heptane-2-carboxylate monohydrate.
Achromycin V (tetracycline HCl) is commercially available from Lederle and is the monohydrochloride of [4S-(4α, 4aα, 5aα; 6/3, 12aα,)]-4- (Dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 6, 10, 12, 12a- pentahydroxy-6- methyl- 1, ll-dioxo-2-naphthacenecarboxamide. Declomycin (demeclocycline HCl) is commercially available from
Lederle Laboratories and is 7-chloro-4-dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 6, 10, 12, 12a-pentahydroxy-l, l l-dioxo-2- naphthacenecarboxamide monohydrochloride.
Dynacin (minocylcine HCl) is commercially available from Medicis and is [4S-(4α, 4aα, 5aα, 12aα)]-4, 7-bis (dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a- octahydro-3, 10, 12, 12a-tetrahydroxy-l, ll-dioxo-2-napthacene carboxamide monochloride.
Minocin (minocycline hydrochloride) is commercially available from Lederle Laboratories and is [4S-(4α, 4aα, 5aα, 12aα)]-4, 7-bis (dimethylamino)- 1, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 10, 12, 12a-tetrahydroxy-l, ll-dioxo-2- napthacene carboxamide monochloride.
Monodox (Doxycycline monohydrate capsules) is commercially available from Oclassen and is α-6-deoxy-5-oxytetracycline.
Terramycin (oxytetracyline) is commercially available from Pfizer. Vectrin (minocycline hydrochloride) is commercially available from
Warner Chilcott Professional Products and is [4S-(4α, 4aα, 5aα, 12ax)]-4, 7-bis (dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 10, 12, 12a- tetrahydroxy-1, ll-dioxo-2-napthacene carboxamide monochloride.
Vibramycin Calcium (doxycycline sodium) is commercially available from Pfizer and is 4-(Dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 5, 10, 12, 12a-pentahydroxy-6-methyl-l, ll-dioxo-2-napthacene-carboxamide monohydrate.
Vibramycin Hyclate (doxycycline hyclate) is commercially available from Pfizer and is c.-6-deoxy-5-oxytetracycrine. Vibramycin Monohydrate (doxycycline monohydrate) is commercially available from Pfizer and is 4-(Dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a- octahydro-3, 5, 10, 12, 12a-pentahydroxy-6-methyl-l, ll-dioxo-2-napthacene- carboxamide monohydrate.
Vibra-Tabs (doxycycline hydrate) is commercially available from Pfizer and is α-β-deoxy-S-oxytetracycline.
Vibramycin (doxycycline) is commercially available from Pfizer and is 4-(Dimethylamino)-l, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 5, 10, 12, 12a- ρentahydroxy-6-methyl- 1, 11 -dioxo-2-napthacene-carboxamide monohydrate.
Lincomycins is monosodium (2S,5R,6R)-6-(3-(2,6-dichlorophenyl)5- methyl-4 -isoxazolecarboxamido]-3,3-dimethyl-7-OXO-4-thia-l- azabicyclo[3.2.0] heptane-2-carboxylate monohydrate.
Cleocin HCl (clindamycin HCl) is commercially available from Pharmacia & Upjohn and is Methyl 7-chloro-6, 7, 8-trideoxy-6-(l-methyl-trα«s- 4-propyl-L-2-pyrrolidine carboxamido)- 1 -thio-L-threo-a-D-galacto- octopyranoside monohydrochloride.
Abelcet (amphotericin B lipid complex) is commercially available from Libosome Company, Inc. and is [IR-(IR*, 3S*, 5R*, 6R*, 9R*5 HR*, 15S*, 16R*, 17R*, 18S*, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R*, 35S*, 36R*, 37S*)]-33-[(3-amino-3, 6-dideoxy-j3-D-mannopyranosyl)-oxy]-l, 3, 5, 6, 9, 11, 17, 37-octahydroxy-15, 16, 18-trimethyl-13-oxo-14, 39-dioxabicyclo [33.3.1] nonatriaconta-19, 21, 23, 25, 27, 29, 31-heptaene-36-carboxylic acid.
AmBisome (amphotericin B) is commercially available from Fujisawa Healthcare and is [IR-(IR*, 3S*, 5R*, 6R*5 9R*, 1 IR*, 15S*, 16R*, 17R*, 18S*, 19E, 21E, 23E, 25E, 27E, 29E, 3 IE, 33R*, 35S*, 36R*, 37S*)]-33-[(3- amino-3, 6-dideoxy-|S-D-mannopyranosyl)-oxy]-l, 3, 5, 6, 9, 11, 17, 37- octahydroxy-15, 16, 18-trimethyl-13-oxo-14, 39-dioxabicyclo [33.3.1] nonatriaconta-19, 21, 23, 25, 27, 29, 31-heptaene-36-carboxylic acid. Amphotec (amphotericin B cholesterol sulfate complex) is commercially available from Sequus Pharmaceuticals, Inc. and is [IR-(IR*, 3S*, 5R*, 6R*, 9R*, HR*, 15S*, 16R*, 17R*, 18S*. 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R*, 35S*, 36R*, 37S*)]-33-[(3-ammo~3, 6-dideoxy-j8-D-mannopyranosyl)-oxy]-l, 3, 5, 6, 9, 11, 17, 37-octahydroxy-15, 16, 18-trimethyl-13-oxo-14, 39-dioxabicyclo [33.3.1] nonatriaconta-19, 21, 23, 25, 27, 29, 31-heρtaene-36-carboxylic acid.
Ancobon (flucytosine) is commercially available from ICN Pharmaceuticals and is 5-fluorocytosine.
Diflucan (fluconazole) is commercially available from Pfizer Inc. and is 2, 4-difluoro-Q!- ol-bis (IH-I, 2, 4-triazol-l-ylmethyl) benzyl alcohol.
Fulvicin P/G (ultramicrosize griseofulvin) is commercially available from Schering.
Fulvicin P/G 165 and 330 (ultramicrosize griseofulvin) is commercially available from Schering. Grifulvin V (griseofulvin) is commercially available from Ortho
Dermatological.
Gris-PEG (griseofulvin ultramicrosize) is commercially available from Allergan.
Lamisil (terbinafme hydrochloride) is commercially available from Novartis and is (E)-N-(6, 6-dimethyl-2-hepten-4-ynyl)-N-methyl- 1 - naphthalenemethanamine hydrochloride.
Nizoral (ketoconazole) is commercially available from Janssen and is cis l-acetyl-4-[4-[[2-(2, 4-di-chlorophenyl)-2-(lH-imidazol-l-yhnethyl)-l, 3- dioxolan-4-yl] methoxy] phenyl] piperazine. Amphotericin B is [IR-(IR*, 3S*, 5R*, 6R*, 9R*, 1 IR*, 15S*, 16R*,
17R*. 18S*, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R*, 35S*, 36R*, 37S*)]-33- [(3-amino-3, 6-dideoxy-j8-D-mannopyranosyl)-oxy]-l, 3, 5, 6, 9, 11, 17, 37- octahydroxy-15, 16, 18-trimethyl-13-oxo-14, 39-dioxabicyclo [33.3.1] nonatriaconta-19, 21, 23, 25, 27, 29, 31-heptaene-36-carboxylic acid. Lotrimin (clotrimazole) is commercially available from Schering and is
1 -(O-Chloro-c^α-diphenyl benzyl)imidazole.
Dapsone tablets (dapsone) is commercially available from Jacobus and is 4, 4'-diaminodiphenyl-sulfone (DDS).
Diflucan (fluconazole) is commercially available from Pfizer and is 2, 4- difluoro-α-α'-bis (IH-1, 2, 4-triazol-l-ylmethyl) benzyl alcohol.
Monistat-Derm cream (miconazole) is commercially available from Ortho Dermatological and is l-[2, 4-dichloro-/3-{(2, 4-dichlorobenzyl) oxy} phenethyl] imidazole mononitrate.
Mycostatin Cream (nystatin) is commercially available from Westwood- Squibb.
Sporanox (itraconazole) is commercially available from Janssen Pharmaceutical and is (±)-l-[(R*)-sec-bvAyl]-4-\p-[[2R*, 45r*)-2-(2, 4- dichlorophenyl)-2-(lH-l, 2, 4-triazol-l-ylmethyl)-l, 3-dioxolan-4-yl] methoxy] phenyl] -1-piperazinyl] phenyl]-Δ2-l, 2, 4, triazolin-5-one mixture with (±)-l-
[(R*ysec-butγl]-4-\p-[[2R*, 45*)-2-(2, 4-dichlorophenyl)-2-(lH-l, 2, 4-triazol- l-ylmethyl)-l, 3-dioxolan-4-yl] methoxy] phenyl] -1-piperazinyl] ρhenyl]-Δ2-l, 2, 4, triazolin-5-one or (±)-l-[(RS)-sec-butyl]-4-[p-[4-[p-[[(2R, 4S)-2-(2, 4- dichlorophenyl)-2-(lH- 1, 2, 3, 4-triazol-l-ylmethy) 1, 3-dioxolan-4-yl] methoxy] phenyl]-l-piperazinyl] phenyl]-Δ2-l, 2, A, triazolin-5-one.
Aralen hydrochloride (chloroquine HCl) is commercially available from Sanofi Pharmaceuticals and is 7-(chloro-4-[[4-diethylamino)-l-methyl butyl] amino] -quinoline dihydrochloride.
Aralen phosphate (chloroquine phosphate) is commercially available from Sanofi Pharmaceuticals and is 7-(chloro-4-[[4-diethylamino)-l-methyl butyl] amino] -quinoline phosphate (1:2).
Daraprim (pyrimethamine) is commercially available from Glaxo Wellcome and is 5-(4-chlorophenyl)-6-ethyl-2, 4-pyrimidinediamine.
Lariam (mefloquine HCl) is commercially available from Roche Laboratories and is (R*, S*)-(±)-ce-2-piperidinyl-2, 8-bis (trifluoromethyl)-4- quinoline methanol hydrochloride.
Plaquenil (hydroxychloroquine sulfate) is commercially available from Sanofi Pharmaceuticals and is 2-[[4-[7-chloro-4-quinolyl) amino] pentyl] ethylamino] ethanol sulfate (1:1). Capastat sulfate (capreomycin sulfate) is commercially available from
Dura Pharmaceuticals.
Myambutol (ethambutol hydrochloride) is commercially available from Lederle Laboratories.
Mycobutin (rifabutin capsules) is commercially available from Pharmacia & Upjohn and is 1', 4-didehydro-l-deoxy-l, 4-dihydro-5'-(2- methylpropyl)-l-oxorifamycin XIV or (95, 12E5 US, \5R, 16S, HR, 18Λ, 19R, 2OS, 21S, 22E, 24Z)-6, 16, 18, 20-tetrahydroxy-l-l'-isobutyl-14-methoxy-7, 9, 15, 17, 19, 21, 25-heptamethyl-spiro [9, 4-(epoxypentadeca [1, 11, 13] trienimino)-2H-furo [T, 3':7, 8] naphth [1, 2-d] imidazole-2, 4'-piρeridine]-5, 10, 26-(3H, 9H)-trione-16-acetate.
Nydrazid (isoniazid injection) is commercially available from Apothecon.
Paser (aminosalicylic acid) is commercially available from Jacobus and is 4-amino-2-hydroxy benzoic acid.
Priftin (rifapentine) is commercially available from Hoechst Marion Roussel and is rifamycin 3-[[(4-cyclo-pentyl-l-piperazinyl) imino] methyl] or 3[N-(4-cyclopentyl-l-piperazinyl)-formimyid.oyl]-2,7-(epoxypentadeca [1, 11, 13] trienirnino)naptho [2,1-b] furan-1, 11 (2H)-dione 21 -acetate. Pyrazinamide tablets (pyrazinamide) is commercially available from
Lederle Laboratories and is the pyrazine analogue of nicotinamide.
Rifadin (rifampin capsules) is commercially available from Hoechst Marion Roussel and is 3-[[(4-methyl-l-piperazinyl) imino] methyl] rifamycin or 5, 6, 9, 17, 19, 21-hexahydroxy-23-methoxy-2, 4, 12, 16, 20, 22-heptamethyl-8- [N-methyl-1-piperazinyl) formimidoyl]-2,7-(epoxy pentadeca [1,11,13] trienimino)naptho [2,1-b] furan-1, 11 (2H)-dione 21 -acetate.
Rifadin IV (rifampin for injection) is commercially available from Hoechst Marion Roussel and is 3-[[3-(4-methyl-l-piperazinyl) formimidoyl]- 2,7-(epoxy pentadeca [1, 11, 13] trienimino) naphtho [2, 1-b] furan-1, 11 (2H)- dione 21 -acetate.
Rifamate (rifampin and isoniazid) is commerically available from Hoechst Marion Roussel and is 3-(4-methyl-l-piperazinyliminomethyl) rifamycin SV (rifampin) and hydrazide of isonicotinic acid (isoniazid).
Rifater (rifampin, isoniazid and pyrazinamide) is commercially available from Hoechst Marion Roussel and is 3-(4-methyl- 1 -piperazinyliminomethyl) rifamycin SV (rifampin), hydrazide of isonicotinic acid (isoniazid), and pyrazine analogue of nicotinamide (pyrazinamide).
Seromycin (cycloserine capsules) is commercially available from Dura Pharmaceuticals and is 3-isoxazolidinone, 4-amino-, (R)-. Streptomycin Sulfate is commercially available from Pfizer and is O-2- deoxy-2-(methylamino)-o;-L-glyucopyransoyl-(l->2)-0-5-deoxy-3-C-formyl-α- L-lyxofuranosyl-(l→4)-N-N'-bis(aminoiminomethyl)-, sulfate (2:3) salt.
Tice BCG (BCG vaccine) is commercially available from Organon and is attenuated live Mycobacterium bovis strains Bacillus of Calmette and Guerin. Cycloserine (seromycin capsules) is commercially available from Dura
Pharmaceuticals and is 3-isoxazolidinone, 4-amino-, (R)-.
Nydrazid (Isoniazid) is commercially available from Apothecon and is the hydrazide of isonicotinic acid.
Urised (Methenamine) is commercially available from Poly Medica.
Trecator-SC (ethionamide tablets) is commercially available from Wyeth-Ayerst and is 2-ethylthioisonicotinamide.
Alferon N (interferon alfa-n3) is commercially available from Interferon Sciences and is interferon alfa-n3 (human leukocyte derived). Crixivan (indinavir sulfate) is commercially available from Merck & Co.,
Inc. and is [1(1S, 2R), 5(S)]-2, 3, 5-trideoxy-N-(2, 3-dihydro-2-hydroxy-l#- inden-l-yl)-5-[2-[[l, 1-dimethylethyl) amino] carbonyl]-4-(3-pyridinyl-methyl)- l-piperazinyl]-2-(phenylmethyl)-D-erythropentonamide sulfate (1:1).
Cytovene (ganciclovir) is commercially available from Roche and is 9- [[2-hydroxy-l (hydroxymethyl) ethoxy] methyl] guanine.
Cytovene-IV (ganciclovir sodium) is commercially available from Roche and is 9- [[2-hydroxy-l (hydroxymethyl) ethoxy] methyl] guanine.
Epivir (lamivudine) is commercially available from Glaxo Wellcome and is (2R5 cis)-4-amino-l-(2-hydroxymethyl-l, 3-oxathiolan-5-yl)-lH)-pyrimidin-2- one.
Famvir (famciclovir) is commercially available from SmithKline Beecham and is 2-[2-(2-amino-9H-purin-9-yl) ethyl]-l, 3-propanediol diacetate.
Flumadine (rimantadine HCl) is commercially available from Forest and is alpha-methyltricyclo-[3.3.1.1/3.7] decane-1-methanamine hydrochloride. Foscavir (foscarnet sodium) is commercially available from Astra and is phosphonoformic acid, trisodium salt.
Hivid (zalcitabine) is commercially available from Roche and is 4- amino-l-beta-D-21, 3', dideoxyribofuranosyl-2-(lH)-pyrimidone or 2',3'- dideoxycytidine. hitron A (interferon alfa-2b) is commercially available from Schering.
Invirase (saquinavir mesylate) is commercially available from Roche Labs and is N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2- quinolylcarbonyl)-L-asparaginyl] amino] butyl-(4aS, 8aS)-isoquinoline-3(S)- carboxamide methanesulfonate. Norvir (ritonavir) is commercially available from Abbott and is 10-
Hydroxy-2-methyl-5-(l-methylethyl)-l-[2-(l-methylethyl)-4-thiazolyl]-3, 6- dioxo-8, ll-bis(phenylmethyl)-2, 4, 7, 12-tetraazatridencan-B-oic acid, 5- thiazolyl methyl ester [5S-(5R*, 8R*, 1OR*, HR*)].
Rebetron combination therapy, which contains Rebetrol (ribavirin which is 1-β-D-ribofuranosyl-lH-l, 2, 4-triazole-3-carboxamide) and Intron A (inteferon alfa-2b), is commercially available from Schering.
Rescriptor (delavirdine mesylate) is commercially available from Pharmacia & Upjohn and is pieperazine, l-[3-[(l-methylethyl) amino]-2- pyridinyl]-4-[[5(methylsulfonyl)-amino]-lH-indol-2-yl] carbonyl], monomethanesulfonate.
Retrovir (ziduvudine) is commerically available from Glaxo Wellcome and is 3'-azido-3'-deoxythymidine. Retrovir IV (zidovudine) is commercially available from Glaxo-
Wellcome and is 3'-azido-3'-deoxythymidine.
Symmetrel (amantadine hydrochloride) is commercially available from Endo Pharmaceuticals and is 1-adamantanamine hydrochloride.
Synagis (palivizumab) is commercially available from Medlmmune Inc. and is humanized monoclonal antibody (IgGl κ).
Valtrex (valacyclovir HCl) is commercially available from Glaxo Wellcome and is L-valine, 2-[(2-amino-l,6-dihydro-6-oxo-9H-purin-9-yl) methoxy] ethyl ester, monohydrochloride.
Videx (didanosine) is commercially available from Bristol-Myers Squibb Oncology/Immunology and is 2',3'-di-deoxyinosine.
Viracept (nelfinavir mesylate) is commercially available from Agouron and is [3S-[2(2S*, 3S*), 3a, 4aft 8a/3]]-N-(l,l-dimethylethyl)decahydro-2-[2- hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-(phenylthio)butyl]-3- isoquinolinecarboxcamide mono-methanesulfonate (salt). Viramune (nevirapine) is commercially available from Roxane and is 11- cyclopropyl-5,1 l-dihydro-4-methyl-6H-dipyrido [3,2-b:2',3'-][l,4] diazepin-6- one.
Virazole (ribavirin) is commercially available from ICN and is 1-beta-D- riboruranosyl- IH-1 ,2,4-triazole-3 -carboxamide. Vistide (cidofovir) is commercially available from Gilead Sciences and is l-[(5)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate (HPMPC).
Zerit (stavudine (d4T)) is commercially available from Bristol-Myers Squibb Oncology/Immunology and is 2l,3l-didehydro-3'deoxythymidine.
Symmetrel Syrup (amantadine HCl) is commercially available from Endo Labs and is 1-adamantanamine hydrochloride.
Combivir Tablets (lamiduvine) is commercially available from Glaxo Wellcome and is 2',3'-didehydro-3'-deoxythymidine. Zovirax (acyclovir) is commercially available from Glaxo Wellcome and is 2-amino-l ,9-dehydro-9-[(2-hydroxyethyoxy)methyl]-6H-purin-6-one.
Dapsone Tablets (dapsone) is commercially available from Jacobus and is 4,4'-diaminodiphenylsulfone (DDS).
Daraprim (pyrimethamine) is commercially available from Glaxo Wellcome and is 5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine.
Flagyl 375 (metronidazole) is commercially available from Searle and is 2-Methyl-5-nitro-imidazole-l-ethanol.
Flagyl ER Tablets (metronidazole) is commercially available from Searle and is 2-Methyl-5-nitro-imidazole-l-ethanol. Flagyl LV. (metronidazole) is commercially available from SCS and is 2-
Methyl-5 -nitro-imidazole- 1 -ethanol.
Furoxone (furazolidone) is commercially available from Roberts and is 3-(5-nitrofurfuryliden-amino)-2-oxazolidinone.
Mepron (atovaquone) is commercially available from Glaxo Wellcome and is trα«5-2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-l,4-naphthalenedione.
Neutrexin (trimetrexate glucuronate) is commercially available from U.S. Bioscience and is 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline mono-D-glucuronate.
Cipro (ciprofloxacin HCl) is commercially available from Bayer and is the monohydrochloride monohydrate salt of 1 -cyclopropyl-ό-fluoro- 1 , 4- dihydro-4-oxo-7-(l -piperazinyl)-3-quinolinecarboxylic acid.
Floxin (ofloxacin) is commercially available from Ortho-McNeil Pharmaceutical and is (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-l- piperazmyl)-7-oxo-7H-pyrido[l,3,3-de]-l,4-benzoxazine-6-carboxylic acid. Levaquin (levofloxacin) is commercially available from Ortho-McNeil
Pharmaceutical) and is (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-l- piperazinyl)-7-oxo-7H-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acid hemihydrate.
Mazaquin (lomefloxacin HCl) is commercially available from Unimed and is monohydrochloride salt of (±)-l-ethyl-6,8-difluoro-l,4-dihydro-7-(3- methyl-l-piperazinyl)-4-oxo-3-quinolinecarboxylic acid.
Noroxin (norfloxacin) is commercially available from Merck and is 1- ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)-3-quinolinecarboxylic acid.
Penetrex (enoxacin) is commercially available from Rhδne-Poulenc Rorer and is l-ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)-l,8- naphthyridine-3-carboxylic acid sesquihydrate.
Raxar (grepafloxacin HCl) is commercially available from Glaxo Wellcome and is (±)-l-cyclopropyl-6-fluoro-l,4-dihydro-5-methyl-7-(3-methyl- l-piperazinyl)-4-oxo-3-quinolinecarboxylic acid monochloride sesquihydrate.
Trovan (trovafloxacin mesylate) is commercially available from Pfizer and is (I D, 5D, 6a)-7-(6-amino-3-azabicyclo[3.1.0]hex-3-yl)-l-(2,4- difluoroρhenyl)-6-fluoro-l,4-dihydro-4-oxo-l,8-naphtliyridme-3-carboxylic acid, monomethanesulfonate.
Zagam (sparfloxacin) is commercially available from Rhδne-Poulenc Rorer and is 5-Amino-l-cyclopropyl-7-m-3,5-dimethyl-l-piperazinyl)-6,8- difluoro-1,4, dihydro-4-oxo-3-quinolinecarboxylic acid.
Bactrim (trimethoprim and sulfamethoxazole) is commercially available from Roche Labs and is 2,4-diamino-5-(3,4,5-trimethoxybenzyl) pyrimidine (trimethoprim) and N1,- (5-methyl-3-isoxazolyl)sulfanilamide (sulfamethoxazole) .
Bactrim DS (trimethoprim and sulfamethoxazole double strength) is commercially available from Roche Labs and is 2,4-diamino-5-(3,4,5- trimethoxybenzyl) pyrimidine (trimethoprim) and N1,- (5-methyl-3- isoxazolyl)sulfanilamide (sulfamethoxazole).
Pediazole (erythromicin ethylsuccinate and sulfisaxazole acetyl) is commercially available from Ross and is erythromicin 2'-(ethyl succinate) and N' acetyl sulfisoxazole (sulfisoxizole is N-(3,4-Dimethyl-5-isoxazolyl)-N-sulfanilyl acetamide.
Septra (trimethoprim and sulfamethoxazole) is commercially available from Monarch and is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4- pyrimidinediarnine (trimethoprim) and 4-amino-N-(5-methyl-3- isoxazolyl)benzenesulfonamide (sulfamethoxazole).
Septra DS (trimethoprim and sulfamethoxazole) is commercially available from Monarch and is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4- pyrimidinediamine (trimethoprim) and 4-amino-N-(5-methyl-3- isoxazolyl)benzenesulfonamide (sulfamethoxazole) . Co-trimoxazole is a combined chemotherapeutic agent consisting of trimethoprim (T) and the sulphonamide sulphamethoxazole (S); their ratio is 1:5. It is bactericidal by virtue of a sequential blockade of the folic acid synthesis in micoorganisms. The antimicrobial spectrum of co-trimoxazole includes many Gram-positive and Gram-negative aerobes, Chlamydias, nocardias, protozoas (Pneumocystis carinii), etc. In addition to its use for Pneumocystis, co- trimoxazole mainly has practical importance against Gram-positive aerobes (urinary tract infections), pneumococci, and haemophilus influenzae (respiratory tract infections and otitis), http://www.infomed.org/100drugs/ctrifram.html.
Bactrim LV. Infusion (sulfamethoxazole) is commercially available from Roche Labs.
Pediazole (erythromicin ethylsuccinate and sulfisoxazole acetyl) is commercially available from Ross and is erythromicin 2'-(ethyl succinate) and N' acetyl sulfisoxazole (sulfisoxizole is N-(3,4-Dimethyl-5-isoxazolyl)-N-sulfanilyl acetamide. Furadantin (nitrofurantoin) is commercially available from Dura and is 1-
[[(5-nitro-2-furanyl)methylene]amino]-2,4-imidazolidinedione.
Macrobid (nitrofurantoin monohydrate macrocrystals) is commercially available from Procter & Gamble Pharmaceuticals and is l-[[[5-nitro-2- furanyl]methylene] amino] -2-4-imidazolidinedione monohydrate. Macrodantin (nitrofurantoin macrocrystals) is commercially available from Procter & Gamble Pharmaceuticals and is l-[[[5-nitro-2- furanyl]methylene] amino]-2-4-iniidazolidinedione.
Monurol Sachet (fosfomycin tromethamine) is commercially available from Forest and is (IR, 2S)-(1, 2-epoxypropyl) phosphonic acid, compound with 2-amino-2-(hydroxymethyl)-l ,3-propanediol (1:1).
NegGram Caplets (nalidixic acid) is commercially available from Sanofi and is 1 -ethyl- l,4-dihydro-7-methyl-4-oxo-l,8-naphthyridine-3-carboxylic acid.
Septra (trimethoprim and sulfamethoxazole) is commercially available from Monarch and is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-
pyriniidinediamine (trimethoprim) and 4-amino-N-(5-methyl-3- isoxazolyl)benzenesulfonamide (sulfamethoxazole).
Septra DS (trimethoprim and sulfamethoxazole) is commercially available from Monarch and is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4- pyrimidinediamine (trimethoprim) and 4-amino-N-(5-methyl-3- isoxazolyl)benzenesulfonamide (sulfamethoxazole).
Urised (a combination of the antiseptics methenamine, methylene blue, phenyl salicylate, benzoic acid and parasympatholytics (atropine sulfate) hyoscyamine) is commercially available from Poly Medica. Urobiotic-250 Capsules (oxytetracycline HCl, sulfamethizole and phenazopyridine HCl) is commercially available from Pfizer.
Uroqid Acid No. 2 Tablets (methenamine mandelate) is commercially available from Beach.
Bactroban (mupirocin) is commercially available from SmithKline Beecham and is (aE, 2S, 3R,4R,5S)-5-[(2S,3SAS,5S)-2,3-Epoxy-5-hydroxy-4- methylhexyl]tetraliydro-3 ,4-dihydroxy-j3-methyl-2H-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2:1), dihydrate.
Chloromycetin opthalmic (chloramphenical) is commercially available from Monarch and is (1) Acetamide, 2,2-dichloro-iV-[2-hydroxy-l- (hydroxymethyl)-2-(4-nitrophenyl) ethyl]-, and (2) D-t/*reø-(-)-2,2-Dichloro-N- [β-hydroxy-α-(hydroxymethyl)-p-nitrophenethyl] acetamide.
Cortisporin (neomycin and polymyxin β sulfates and hydrocortisone acetate cream) is commercially available from Monarch and is 21-(acetyloxy)- 1 IB, 17-dihydroxypregn-4-ene-3 ,20-dione. Ilotycin (erythromycin opthalmic ointment) is commercially available from Dista and is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4- [(2, β-dideoxy-S-C-methyl-S-O-methyl-α-L-rfόo-hexopyranosyl) oxy]-14-ethyl- 7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3- (dimethylamino)-j3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
NeoDecadron (neomycin sulfate - dexamethasone sodium phosphate) is commercially available from Merck and is 9-fluoro-llj8, 17-dihydroxy-16ce- methyl-21-(phosphonooxy)pregna-l, 4-diene-3, 20-dione disodium salt.
Polytrim (trimethoprim and polymyxin β sulfate opthalmic solution) is commercially available from Allergan and is 2,4-diamino-5-(3 ,4,5- trimethoxylbenzl)pyrimidine (trimethoprim) and the sulfate salt of polymyxin B1 and B2 (polymyxin β sulfate). Terra-Cortril (oxytetracycline HCl and hydrocortisone acetate) is commercially available from Pfizer.
TobraDex (tobramycin and dexamethasone opthalmic suspension and ointment) is commercially available from Alcon and is O-3-Amino-3-deoxy-a- D-glucopyranosyl-(l ->4)-O- [2,6-diamino-2,3,6-trideoxy-a-D-πδo- hexopyranosyl-l(l-»6)] -2-deoxy-L-streptamine. Dexamethasone: Chemical Name: 9-Fluro- 1 Ib, 17,21 -trihydroxy- 16a-methylpregna- 1 ,4-diene-3,20-dione. Vira-A opthalmic ointment, 3% (vidarabine) is commercially available from Monarch and is 9H-Purin-6-arnine, 9-β-D-arabinofuranosyl-, monohydrate.
Chibroxin (norfloxacin opthalmic solution) is commercially available from Merck and is l-ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)-3- quinolinecarboxylic acid.
Ciloxan opthalmic solution, (Ciprofloxacin HCl) is commercially available from Alcon and is the monohydro chloride monohydrate salt of 1- cyclopropyl-6-fluoro-l, 4-dihydro-4-oxo-7-(l-piperazinyl)-3-quinoline- carboxylic acid.
Ciloxan opthalmic ointment, (Ciprofloxacin HCl) is commercially available from Alcon and is the monohydro chloride monohydrate salt of 1- cyclopropyl-6-fluoro-l, 4-dihydro-4-oxo-7-(l-piperazinyl)-3-quinoline- carboxylic acid. Ocuflox opthalmic solution (ofloxacin) is commercially available from
Allergan and is (±)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-l-piperazinyl)- 7-oxo-7 H-pyrido[l,2,3-de]-l,4 benzoxazine-6-carboxylic acid.
Blephamide opthalmic ointment (sulfacetamide sodium and prednisolone acetate) is commercially available from Allergan and is N-sulfanilyl-acetamide monosodium salt monohydrate (sulfacetamide sodium) and 11 β, 17,21 - trihydroxypreyna-1, 4-diene-3,20-dione 21-acetate (prednisolone acetate).
Blephamide opthalmic suspension (sulfacetamide sodium and prednisolone acetate) is commercially available from Allergan and is N- sulfanilyl-acetamide monosodium salt monohydrate ( sulfacetamide sodium) and
lljδ,17,21-trihydroxypreyna-l, 4-diene-3,20-dione 21-acetate (prednisolone acetate).
A/T/S (erythromycin) is commercially available from Hoescht Marion Roussel and is (3R*. 4S*, 5S*, 6R*, 7R*, 9R*5 HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-0-methyl-o;-L-n&o-hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3- (dimethylamino)-j8-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
Bactroban (mupirocin) is commercially available from SKB and is (oiE, IS, 3i?,4i?,55)-5-[(2S,35',4S,55)-2,3-Epoxy-5-hydroxy-4-methylhexyl]tetrariydro- 3,4-dihydroxy-|8-methyl-2H-pyran-2-crotonic acid, ester with 9- hydroxynonanoic acid, calcium salt (2:1), dihydrate.
Benzamycin (erythromycin-benzoyl peroxide topical gel) is commercially available from Dermik and is (3R*, 4S*5 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-a-L-nbo- hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3-(dimethylamino)-/3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10-dione (erythromycin).
Betadine (povidone-iodine) is commercially available from Purdue Frederick.
Cleocin T (clindamycin phosphate topical solution) is commercially available from Pharmacia & Upjohn and is L-t&reo-I-D-gα/αcto-Octopyranoside, methyl 7-chloro-6,7,8-trideoxy-6- [[(l-methyl-4-propyl-2-pyrrolidinyl)- carbonyl] amino]-l-thio-, 2-(dihydrogen phosphate), (2S-trans)-. Clindets (clindamycin phosphate pledgets) is commercially available from Stiefel and is methyl 7-chloro-6,7,8-trideoxy-6-(l-methyl-trans-4-propyl-L- 2-pyrrolidinecarboxamido)- 1 -thio-L-tAreo- D -D-gα/αcto-octopyranoside 2- (dihydrogen phospate).
Emgel (erythromycin) is commercially available from Glaxo Wellcome and is (3R*,4S*,5S*,6R*> 7R*,9R*Λ li?*,12i?*,135*,14Λ*)-4-[(2,6-Dideoxy-3- C-methyl-3-O-methyl-α-L-rzόo-hexopyranosyl)oxy]-14-ethyl-7,12,13- trihydroxy-3,5,7,9, 11 , 13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethyl-amino)-/3- D-xy/o-hexopyranosyl] oxy] oxacyclotetradecane-2, 10-dione.
Erycette (erythromycin topical solution) is commercially available from
Ortho Dermatological and is (3R*,4$*,5$*,6R*,
7i?*,9i?*,lli?*,12JR*,13JS*,14i?*)-4-[(2,6-Dideoxy-3-C-methyl-3-O-methyl-o:-L- πόo-hexopyranosyl)oxy] - 14-ethyl-7, 12, 13-trihydroxy-3 ,5 ,7,9, 11 , 13- hexamethyl-6-[[3 ,4,6-trideoxy-3-(dimethyl-amino)-/3-D-xy/o- hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione.
Klaron (sodium sulfacetamide lotion) is commercially available from Dermik.
Mycostatin (nystatin cream) is commercially available from Westwood- Squibb.
Theramycin Z (erythromycin topical solution) is commercially available from Medicis and is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)- 4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-o;-L-π'&o-hexopyranosyl) oxy]-14- ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3- (dimethylamino)-/3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
T-Stat (erythromycin) is commercially available from Westwood-Squibb and is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, HR*, 12R*, 13S*, 14R*)-4-[(2, 6- dideoxy-3-C-methyl-3-O-methyl-ce-L-π&o-hexopyranosyl) oxy]-14-ethyl-7, 12, 13-trihydroxy-3, 5, 7, 9, 11, 13, hexamethyl-6-[[3, 4, 6-trideoxy-3-
(dimethylamino)-/3-D-xy/o-hex-opyranosyl] oxy] oxacyclotetradecane-2, 10- dione.
Exelderm (sulconazole nitrate) is commercially available from Westwood-Squibb and is (±)-l-[2,4-dichloro-|8-[(p-chlorobenzyl)-thio]- plenethyl] imidazole mononitrate;
Fungizone (amphotericin B oral suspension) is commercially available from Bristol-Myers Squibb and is [1R-(1R*,3S*,5R*,6R*,9R*,11R*, 15S*,16R*,17R*,18S*,19E,21E,23E,25E,27E,29E,31E,33R*,35S*,36R*,37S*)] -33-[(3-Amino-3,6-dideoxy-/3-D-mannopyranosyl)-oxy]-l,3,5,6,9,ll,17,37- octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo [33.3.1] nonatriaconta- 19,21 ,23,25 ,27,29,31 -heptaene-36-carboxylic acid.
Lamisil (terbinafme hydrochloride cream) is commercially available from Novartis and is (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-l- naphthalenemethanamine hydrochloride.
Loprox (ciclopiroxolamine) is commercially available from Hoescht Marion Roussel and is 6-cyclohexyl-l-hydroxy-4-methyl-2(lH)-pyridone, 2- amino-ethanol salt.
Lotrimin (clotrimazole) is commercially available from Schering and is l-(O-Chloro-α,α-diphenyl benzyl)imidazole.
Lotrisone (clotrimazole and betamethasone diproprionate) is commercially available from Schering and is l-(O-Chloro-o!,O!-diphenyl benzyl)imidazole (clotrimazole) and 9-Fluoro-l 1/3,17,21-trihroxy- 16/3- methylpregna- 1 ,4-diene-3 ,20-dione 17,21 -diproprionate (betamethasone diproprionate).
Mentax (butenafme HCl) is commercially available from Penederm and is N-4-tert-butylbenzyl-N-methyl- 1 -naphthalenemethylamine hydrochloride.
Monistat-Derm (miconazole nitrate) is commercially available from Ortho Dermatological and is l-[2,4-dichloro-/3-{(2,4- dichlorobenzyl)oxy)}phenethyl]imidazole mononitrate.
Mycelex (clotrimazole) is commercially available from Alza and is [l-(o- chloro-α,Q!-diphenylbenzyl) imidazole.
Mycostatin (nystatin) is commercially available from Westwood-Squibb.
Naftin (naftifine HCl) is commercially available from Allergan and is (E)-N-Cinnamyl-N-methyl-l-naphthalene-methylamine hydrochloride.
Nizoral (ketoconazole) is commercially available from Janssen and is cis- l-acetyl-4[4-[[2-(2,4-dichorophenyl)-2-(lH-imidazol-l-ylmethyl)-l,3-dioxolan- 4-yl]methoxy]phenyl]piperazine.
Nystop (nystatin) is commercially available from Paddock. Oxistat (oxiconazole nitrate) is commercially available from Glaxo
Wellcome and is 2',4'-dichloro-2-imidazole-l-ylacetophenone (Z)-[O-(2,4- dichlorobenzyl)oxime] , mononitrate.
Selsun Rx (2.5% selenium sulfide lotion) is commercially available from Ross. Spectazole (econazole nitrate) is commercially available from Ortho
Dermatological and is l-[2-{(4-chorophenyl) methoxy}-2-(2,4-dichlorophenyl)- ethyl]-lH-imidazole mononitrate.
Denavir (penciclovir cream) is commercially available from SmithKline Beecham and is 9-[4-hydroxy-3-(hydroxymethyl) butyl]guanine.
Zovirax (acyclovir) is commercially available from Glaxo-Wellcome and is 2-amino- 1 ,9-dihydro-9-(2-hydroxyethoxy)memyl-6H-ρurin-6-one.
Benzashave (benzoyl peroxide) is commercially available from Medicis.
Betadine (povidone-iodine) is commercially available from Purdue Frederick.
Betasept (chlorhexidine gluconate) is commercially available from Purdue Frederick.
Cetaphil (soap substitute) is commercially available from Galaderma.
Clorpactin WCS-90 (sodium oxychlorosene) is commercially available from Guardiam Laboratories.
Dapsone Tablets (dapsone) is commercially available from Jacobus and is 4,4'-diaminodiphenyl sulfone (DDS).
Desquam-E (benzoyl peroxide) is commercially available from Westwood-Squibb. Desquam-X (benzoyl peroxide) is commercially available from
Westwood-Squibb.
Hibiclens (chlorhexidine gluconate) is commercially available from Zeneca.
Hibistat (chlorhexidine gluconate) is commercially available from Zeneca. hnpregon (tetrachlorosalicylanilide 2%) is commercially available from Fleming.
MetroCream (metronidazole) is commercially available from Galaderma and is 2-methyl-5-nitro-lH-imidazole-l-ethanol. MetroGel (metronidazole) is commercially available from Galaderma and is 2-methyl-5-nitro-lH-imidazole-l-ethanol.
Noritate (metronidazole) is commercially available from Dermik and is 2-methyl-5-nitro-l/f-imidazole-l-ethanol. pHisoHex (hexachlorophene detergent cleanser) is commercially available from Sanofi and is Phenol,2,2'-methylene-bis[3,4,6-trichloro-].
Sulfacet-R (sodium sulfacetamide 10% and sulfur 5%) is commercially available from Dermik.
Sulfamylon (matenide acetate) is commercially available from Bertek and is α-amino-p-toluenesulfonamide monoacetate.
Triaz (benzoyl peroxide) is commercially available from Medicis.
Vanoxide-HC (benzoyl peroxide hydrocortisone) is commercially available from Dermik and is 11/3,17,2 l-trihydroxypregn-4-ene-3,20-dione (hydrocortisone) . Acticin (permethrin) is commercially available from Penederm and is
(±)-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropanecarboxylate.
Elimite (permethrin) is commercially available from Allergan and is (±)- 3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate. Eurax (crotamiton) is commercially available from Westwood-Squibb and is N-ethyl-N-(o-methylphenyl)-2-butenamide.
Lindane Lotion USP 1% (lindane) is commercially available from Alpharma.
Efudex (fluorouracil) is commercially available from ICN and is 5- flouro-2,4 (IH, 3H)-pyrimidinedione.
Fluoroplex (fluorouracil) is commercially available from Allergan and is 5-flouro-2,4 (IH, 3H)-pyrimidinedione.
Furadantin Oral Suspension (nitrofurantoin) is commercially available from Dura and is l-[[5-nitro-2-furanyl)methylene]amino]-2,4-imidazolidine dione.
Zyvox (linezolid) is commercially available from Pharmacia & Upjohn.
It is appreciated that those skilled in the art understand that the antibiotic useful in the present invention is the biologically active compound present in any of the antibiotic drugs disclosed above. For example, Azactam (aztreonam) is typically available as an injectable solution. The antibiotic, however, is (z)-2- [[[(2-amino-4-thiazolyl) [[(2S,-3S)-2-methyl-4-oxo-l-sulfo-3-azetidinyl] carbamoyl] methylene] amino] oxy]-2-methyl propionic acid. Physician's Desk Reference (PDR), Medical Economics Company (Montvale, NJ), (53rd Ed.), pp. 820-823, 1999.
The formulation 5 can further include alpha carotene, beta carotene, vitamin A, or a combination thereof; in any suitable and effective amount.
Referring to Figures 1-10, an adhesive patch 1 of the present invention is provided. The adhesive patch 1 includes a formulation 5 located on at least a
portion of the front side 3 of the backing 2, in at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. Preferably, the formulation 5 is partially embedded in at least a portion of the front side 3 of the backing 2. In addition to being located in at least a portion of the front side 3 of the backing 2, the formulation 5 is located on a portion of the surface of front side 3 of the backing 2. Preferably, the formulation 5 is located on the entire surface of the front side 3 of the backing 2.
Backing The backing 2 is defined by a front side 3 (the side exposed to the skin during use) and a back side 4 (the side exposed to the environment during use). The backing 2 should be nonirritating to human skin. The backing 2 is a self- supporting sheet of water soluble or water insoluble, polymeric or natural material that provides strength and integrity for the formulation 5. The backing 2 of the adhesive patch 1 can be vapor permeable. The backing 2 can also be porous, since porosity provides openings for receiving the formulation 5 and it helps to assure that the adhesive skin patch 1 is vapor permeable. Specifically, the backing 2 can retain the formulation 5 while allowing moisture from the skin to pass. Alternatively, the backing 2 of the adhesive patch 1 can be vapor impermeable. The backing 2 can also be non-porous, which would increase the amount of skin absorption of the xanthophylls 15. Specifically, the backing 2 can retain the formulation 5 while not allowing moisture from the skin to pass. The backing 2 can have any suitable thickness, provided the suitable thickness allows for a flexible, bendable, pliable, and/or a stretchable sheet of water insoluble material. Specifically, the thickness of the backing 2 can be about 0.001 mm to about 5.0 mm, about 0.001 mm to about 3.0 mm, or about 0.025 mm to about 1.25 mm.
The backing 2 can be manufactured from any suitable material, provided the suitable material can form a flexible, bendable, pliable, and/or stretchable backing 2. The backing 2 includes a flexible sheet of water soluble or water insoluble material that provides support for the adhesive skin patch 1. The backing 2 can include water soluble or water insoluble polymeric fibers, a porous film, or any other kind of matrix with spaces within the matrix. A
specific backing 2 is a lightweight, porous, pliable strip composed of a nonwoven fabric of polymeric or natural fibers such as polyester, cotton or cellulose fibers bonded together with a sizing resin. The backing 2 can be woven or nonwoven. Preferably, the backing 2 includes nonwoven fabric. Specifically, the backing 2 can include polyester fibers, polyurethane fibers, polyolefm fibers, polyamide fibers, natural fibers, cotton fibers, copolyester fibers, cellulose acetate fibers, polycellulose fibers, or any mixture thereof. Additional stable, water insoluble flexible sheet materials and methods for manufacturing the suitable backings 2 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein, and are suitable as backings 2 according to the present invention. The infusion of the formulation 5 into the backing 2 can be accomplished, e.g., with the use of a continuous process mixer, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein; or as discussed herein.
Alternatively, the backing 2 can be a non-woven backing 2 that is treated by coating: the front side 3 of the backing adhesive patch 1, the back side 4 of the backing 2, or both the front side 3 and back side 4 of the backing 2; with a silicone-containing compound, a fluorocarbon solution, or a combination thereof. Suitable silicone-containing compounds include, e.g., polydimethyl siloxanes, dialkylsiloxanes, dimethylsiloxo vinyl alkenes, dialkylsiloxo vinyl alkenes, dimethylsiloxo acrylates, dialkylsiloxo acrylates, vinyl terminated polydimethylsiloxane, and vinyl terminated polydialkylsiloxane. The exemplary silicone-containing compounds are commercially available from, e.g., Goldschmidt Chemical Corp. (Essen, Germany); GE Silicones (Waterford, NY); Wacker Silicone Corp. (Adrian, MI); and Dow Corning Corp. (Midland, MI). The backing 2 can be manufactured from a suitable non-woven fabric that is commercially available from, e.g., Freudenberg Faservliesstoffe KG (Weinham, Germany); Sontara Technologies (division of DuPont Corporation) (Old Hickory, TN); Lystil S. A. (Brignoud Cedex, France); Dexter Nonwovens (Windsor Locks, CT); and Chicopee (New Brusnwick, NJ). Other commercial vendors that supply suitable non-woven fabrics can be found at the Technical Textile website (http://www.technical-textiles.net/technical-textiles- index/orgL.htm) .
It has surprisingly been discovered that the use of a treated backing, such as a fluorocarbon treated non- woven backing, typically increases the yield of an adhesive patch. The use of a backing material that has been treated with a sizing agent allows for the effective control of the rate of penetration, such that the gel or ointment has solidified after it has begun to penetrate the backing, but before it has passed completely through the backing, hi addition, the use of a backing material that has been treated with a sizing agent allows for the effective control of the depth to which the ointment or gel will easily penetrate before solidifying. It has surprisingly been discovered that increasing the control of the rate at which the ointment or gel penetrates the backing typically improves the overall yield of the production process by reducing the amount of material which must be discarded because the back side of the backing has become too tacky for either processing or for consumer acceptance.
At least a portion of the backing 2 can be treated with a sizing agent 8 such that the portion of the backing 2 that is treated with the sizing agent 8 has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. Specifically, the portion of the backing 2 that is treated with the sizing agent 8 can have a surface energy of about 27 dynes/cm2 to about 56 dynes/cm2. The sizing agent 8 lowers the surface energy of the portion of the backing 2 that is treated with the sizing agent 8. Any suitable sizing agent 8 can be employed, provided the portion of the backing 2 that is treated with the sizing agent 8 has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. Suitable sizing agents 8 include, e.g., fluorocarbon solutions, silicone-containing compounds, and combinations thereof. Specifically, the backing 2 can be a non-woven backing 2 that is treated with a fluorocarbon. For example, the fluorocarbon treated backing 2 can be, e.g., Vilmed M1585 W/HY, Vilmed M1585H/HY, Vilmed M1586 WfHY, Vilmed M1586 H/HY, Vilmed M1570, Vilmed M1573 F, Vilmed M1573 FH, Vilmed Ml 577 F, Vilmed Ml 578 F, or Vilmed Ml 578 FH; which are all commercially available from Freudenberg Faservliesstoffe KG (Weinham, Germany). Alternatively, the silicone treated backing 2 can be a non-woven backing 2 that is coated with one or more silicone-containing compounds, e.g., a polydimethyl siloxane, a dialkylsiloxane, a dimethylsiloxo vinyl alkene, a dialkylsiloxo vinyl alkenes, a dimethylsiloxo acrylate, a dialkylsiloxo acrylate, a
vinyl terminated polydimethylsiloxane, and a vinyl terminated polydialkylsiloxane.
At least a portion of the backing 2 can be treated with the sizing agent 8. The portion of the backing 2 that is treated with the sizing agent 8 can be that portion of the backing 2 that can typically include the formulation 5. The entire surface of the front side 3 of the backing 2 can be treated with the sizing agent 8 or a portion of the surface of the front side 3 of the backing 2 can be treated with the sizing agent 8. Preferably, the entire surface of the front side 3 of the backing 2 can be treated with the sizing agent 8. In addition to the surface of the front side 3 of the backing 2 being treated with the sizing agent 8, the sizing agent 8 can penetrate at least a portion of the underlying surface (e.g., one-tenth to about nine-tenths the thickness, or about one-fourth to about nine-tenths the thickness) of the backing 2. Specifically, the sizing agent 8 can penetrate the entire underlying surface of the backing 2. Suitable fluorocarbon treated backings 2 include, e.g., Vilmed M1585
W/HY, Vilmed M1585H/HY, Vilmed M1586 W/HY, Vilmed M1586 H/HY, Vilmed Ml 570, Vilmed Ml 573 F, Vilmed Ml 573 FH, Vilmed Ml 577 F, Vilmed Ml 578 F, and Vilmed Ml 578 FH; which are all commercially available from Freudenberg Faservliesstoffe KG (Weinham, Germany). As shown in Figs. 1-6 and 9-10, the backing 2 includes a front side 3 and a back side 4. The adhesive skin patch 1 includes a formulation 5 located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the formulation 5 can be located on the entire surface of the front side 3 of the backing 2 or the formulation 5 can be located on a portion of the surface of the front side 3 of the backing 2.
Preferably, the formulation 5 can be located on the entire surface of the front side 3 of the backing 2. m addition to being located on the surface of the front side 3 of the backing 2, the formulation 5 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the formulation 5 can be partially embedded into the backing 2).
As shown in Figure 9, the formulation 5 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the formulation 5 can
penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2. As such, the formulation 5 can be partially embedded into the backing 2. Preferably, the formulation 5 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the formulation 5 is partially embedded into the backing 2).
Alternatively, a portion of the front side 3 of the backing 2 can include the formulation 5 and other portions of the front side 3 of the backing 2 can include any combination of the pressure sensitive adhesive 14 and solvent 13. For example, a central circular portion of the front side 3 of the backing 2 can include the formulation 5 while the remaining portions of the front side 3 of the backing 2 include only the pressure sensitive adhesive 14. The formulation 5, when partially embedded into the front side 3 of the backing 2, imparts strength and structure into the adhesive patch 1. For example, when the formulation 5 is partially embedded into the backing 2, the likelihood that the adhesive patch 1 will tear apart when separated from the release liner 10 or when removed from the skin after use, is minimized.
When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the formulation 5 can be in continuous contact with the skin surface of the patient.
In one embodiemnt, the adhesive skin patch 1, upon contact with skin, will allow the skin to breathe. More preferably, the adhesive skin patch 1, upon prolonged contact with skin, will hold in place the formulation 5 and will permit the skin to breathe over prolonged periods of time typically experienced with the use of the patch, e.g., up to about 24 hours, up to about 12 hours, up to about 8 hours, or up to about 6 hours.
As shown in Figs. 3-6 and 9, the adhesive skin patch 1 can be reversibly attached to a release liner 10. The release liner 10 helps to maintain the adhesiveness of the adhesive skin patch 1 prior to use, such as during manufacturing, packaging, shipping, and/or storage. Any suitable release liner 10 can be employed for use in the present invention. Suitable release liners 10 are readily known to those of skill in the art. See, e.g., U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein for further descriptions of release
liners 10 useful in the present invention. The release liner 10 can include a perforation 12 that allows the tab section 11 of the release liner 10 to be removed (see, Figs. 3, 5, and 6). Removal of the tab section 11 of the release liner 10 allows the adhesive skin patch 1 to be removed from the release liner 10 with relative ease.
Xanthophylls
As used herein, "xanthophylls" 15 refers to any of several yellow accessory pigments which found in plant leaves, egg yolks and human blood plasma, these pigments are oxygenated derivatives of carotenes and are involved in photosynthesis, for example lutein, violaxanthin and neoxanthine. In one embodiment, the xanthophylls 15 can be derived from alfalfa, clove, kale, spinach, squash, black bean tops, sea-weed, leafy green vegetable, or any combination thereof. Specifically, the xanthophylls 15 can include lutein, zeaxanthin, or a combination thereof.
Any suitable xanthophylls 15 can be employed provided:
(1) the xanthophylls 15 has the desired therapeutic and/or prophylactic properties (e.g., the xanthophylls 15 effectively treats wrinkles); and
(2) the xanthophylls 15 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. The specific xanthophylls 15 will preferably be non-toxic to mammals (e.g., humans) and will be suitable for medicinal use (e.g., topically and/or via inhalation). The specific xanthophylls 15 will also preferably comply with any controlling or governing body of law, e.g., FDA regulations.
As used herein, "lutein" refers to a compound having the formula:
which is chemically designated as (3R, 3'R, 6'R)-j3,e-carotene-3,3'-diol. Lutein is a substance of a strongly marked yellow colour, extracted from the yolk of
eggs, and from the tissue of the corpus luteum. Lutein is not made in the body and must be obtained from food or vitamin supplements. Lutein is found in large amounts in green, leafy vegetables such as spinach; and legumes such as alfalfa.
The esterified form of lutein refers to a compound having the formula:
wherein Rl and R2 are radicals derived from fatty acids such as palmitic acid. As used herein, "zeaxanthin" refers to a compound having the formula:
which is chemically designated as beta-carotene-3,3'-diol. Zeaxanthin is a carotene found in corn, fruits, seeds, and egg yolk.
The xanthophylls 15 can be present in any appropriate and suitable amount, provided:
(1) the amount of xanthophylls 15 has the desired therapeutic and/or prophylactic properties (e.g., the xanthophylls 15 effectively kills or inactivates an airborne pathogen, respiratory tract pathogen, or a combination thereof); and
(2) the amount of xanthophylls 15 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. The specific amount of xanthophylls 15 will preferably be non-toxic to mammals (e.g., humans) and will be suitable for medicinal use (e.g., topically and/or via inhalation). The specific amount of xanthophylls 15 will also preferably comply with any controlling or governing body of law, e.g., FDA regulations.
Typically, the amount of xanthophylls 15 present in the formulation 5 will depend upon the specific compound or compounds employed as the xanthophylls 15. Specifically, the xanthophylls 15 can be present in about 0.01 wt.% to about 99.9 wt.% of the formulation 5. More specifically, the xanthophylls 15 can be present up to about 50 wt.% of the formulation 5, up to about 25 wt.% of the formulation 5, up to about 20 wt.% of the formulation 5, up to about 10 wt.% of the formulation 5, or up to about 5 wt.% of the formulation 5.
The adhesive skin patch 1 includes an xanthophylls 15 located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the xanthophylls 15 can be located on the entire surface of the front side 3 of the backing 2 or the xanthophylls 15 can be located on a portion of the surface of the front side 3 of the backing 2. Preferably, the xanthophylls 15 can be located on the entire surface of the front side 3 of the backing 2.
In addition to being located on the surface of the front side 3 of the backing 2, the xanthophylls 15 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the xanthophylls 15 can be partially embedded into the backing 2). As shown in Figure 9, the xanthophylls 15 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the xanthophylls 15 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine- tenths the thickness of the backing 2. As such, the xanthophylls 15 can be partially embedded into the backing 2.
Preferably, the xanthophylls 15 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the xanthophylls 15 is partially embedded into the backing 2). Alternatively, a portion of the front side 3 of the backing 2 can include the xanthophylls 15 and other portions of the front side 3 of the backing 2 can include the pressure sensitive adhesive. For example, a central circular portion of the front side 3 of the backing 2 can include the xanthophylls 15 while the remaining portions of the front side 3 of the backing 2 include only the pressure sensitive adhesive 14.
When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the xanthophylls 15 can be in continuous contact with the skin surface of the patient.
As used herein, "treating" or "treat" includes (i) preventing a pathologic condition (e.g., respiratory infection) from occurring (e.g. prophylaxis); (ii) inhibiting the pathologic condition (e.g., respiratory infection) or arresting its development; and (iii) relieving the pathologic condition (e.g., respiratory infection), or symptoms related to the pathologic condition.
As used herein, "mammal" refers to a class of vertebrate animals of more than 15,000 species, including humans, distinguished by self-regulating body temperature, hair, and in the females, milk-producing mammae. Specifically, mammal can refer to a human.
Solvent When present, the solvent 13 can act as a carrier for, and preferably can dissolve, the xanthophylls 15 and/or the pressure sensitive adhesive 14. Any suitable solvent 13 can be employed, provided the solvent 13 effectively dissolves the xanthophylls 15 and/or the pressure sensitive adhesive 14 and the solvent 13 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
The solvent 13 can include one or more organic compounds, one or more inorganic compounds, or mixtures thereof. Preferably, the solvent 13 will include one or more organic compounds, e.g., esters, terpenes, alcohols, ketones, aldehydes, fatty acids, partially or fully esterified fatty acids, wherein the structures are cyclic, non cylcic (e.g., alkyl), alicyclic (i.e., a bridged ring compound), or aromatic, as well as organic compounds having combinations of these functional groups. Suitable exemplary solvents 13 are disclosed, e.g., in Aldrich Handbook of Fine Chemicals, 2000-2001 (Milwaukee, WI).
Preferably, the solvent 13 includes a polyhydric alcohol, water, or a combination thereof. The polyhydric alcohol can be erythritol, propylene glycol, ethylene glycol, Methylene glycol, or a combination thereof. Erythritol is commercially available from Cragill (Minnetonka, Minnesota). Additional
suitable solvents 13 include, e.g., glycerin; triacetin; diethylene glycol methyl ether; diethylene glycol methyl ether acetate; 1,3-propane diol; 2-methyl-l,3- propane diol; glycerol ricinoleate; PEG-6 caprylic / capric glycerides; caprylic / capric triglycerides; propyleneglycol dicaprylate / dicaprate; glycerol monostearate; glycerol monocaprylate; glycerol monolaurate; neopentyl alcohol; 1-hexadecanol; hydroxypropyl beta-cyclodextrin; vitamin E; vitamin E acetate; deoxycholic acid; taurodeoxycholic acid; 3-[(3-cholamidopropyl) dimethylammonio]-l-propane-sulfonate; BigCHAP; cholic acid; cholesterol NF; propylene carbonate; lecithin; a medicinally acceptable salt thereof; or a combination thereof.
When present, the solvent 13 can be employed in any suitable amount, provided the amount of solvent 13 is effective to dissolve the xanthophylls 15 and/or the pressure sensitive pressure sensitive adhesive 14 and the effective amount of solvent 13 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Specifically, the solvent 13 can be present in about 1.0 wt% to about 70.0 wt.%; in about 3.0 wt% to about 50.0 wt.%; or in about 5 wt.% to about 30 wt.% of the formulation 5. Typically, the amount of solvent 13 will depend on the compound or compounds employed as the solvent 13. For example, apolyhydric alcohol can be present up to about 70 wt.% of the formulation 5; or in about 20.0 wt.% to about 60.0 wt.% of the formulation 5; and water can be present in about 2.0 wt.% to about 50.0 wt.% of the formulation 5. When present, the solvent 13 can be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the solvent 13 can be located on the entire surface of the front side 3 of the backing 2 or the solvent 13 can be located on a portion of the surface of the front side 3 of the backing 2. Preferably, the solvent 13 can be located on the entire surface of the front side 3 of the backing 2. In addition to being located on the surface of the front side 3 of the backing 2, the solvent 13 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the solvent 13 can be partially embedded into the backing 2).
As shown in Figure 9, the solvent 13 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the solvent 13 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2. As such, the solvent 13 can be partially embedded into the backing 2. Preferably, the solvent 13 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the solvent 13 is partially embedded into the backing 2). Alternatively, a portion of the front side 3 of the backing 2 can include the solvent 13 and other portions of the front side 3 of the backing 2 can include any combination of the pressure sensitive adhesive 14 and xanthophylls 15. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the solvent 13 can be in continuous contact with the skin surface of the patient.
Pressure Sensitive Adhesive
The formulation 5 can further include a pressure sensitive adhesive. Any suitable pressure sensitive adhesive 14 can be employed, provided the pressure sensitive adhesive 14 provides the requisite adhesiveness to the adhesive skin patch 1 and the pressure sensitive adhesive 14 remains stable in the formulation 5.
Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. It is appreciated that the suitable pressure sensitive adhesives 14 are known to those skilled in the art. Suitable pressure sensitive adhesives 14 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein. Preferably the pressure sensitive adhesive 14 is an acrylic ester copolymer. Any suitable amount of pressure sensitive adhesive 14 can be employed, provided the amount of pressure sensitive adhesive 14 effectively provides the requisite adhesiveness to the adhesive skin patch 1 and the effective amount of the pressure sensitive adhesive 14 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3
years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. The formulation 5 can include a pressure sensitive adhesive 14 in about 0.1 wt.% to about 50 wt.%, in about 0.5 wt.% to about 10.0 wt.%, or in about 1.0 wt.% to about 15.0 wt. % of the formulation 5.
Typically, the suitable amount of pressure sensitive adhesive 14 will depend upon the specific pressure sensitive adhesive 14 employed. For example, the pressure sensitive adhesive 14 can include one or more acrylic ester copolymers. Each of the one or more acrylic ester copolymers can be present up to about 20.0 wt.% of the formulation 5. Specifically, each of the acrylic ester copolymers can be present up to about 40.0 wt.% of the formulation 5, or up to about 30.0 wt.% of the formulation 5. More specifically, all of the one or more acrylic ester copolymers, when combined, can be present in about 3.0 wt.% to about 40.0 wt.% of the formulation 5, or in about 5.0 wt.% to about 30.0 wt.% of the formulation 5. As such, the total amount of acrylic ester copolymers can be about 3.0 wt.% to about 40.0 wt.% of the formulation 5, or about 5.0 wt.% to about 30.0 wt.% of the formulation 5.
Alternatively, the pressure sensitive adhesive 14 can include a hot melt pressure sensitive adhesive 14 or solvent based pressure sensitive adhesive 14 (e.g., polyacrylate, polyisobutylene, and polybutene), rubber, silicone based pressure sensitive adhesives 14 (e.g., polydimethylsiloxane and resin mixtures), polystyrene-polybutadiene-polystyrene, polystyrene-polyisoprene-polystyrene, polystyrene-poly(ethylene-butylene)-polystyrene block polymers, or any combination thereof. Li addition, the adhesive 14 can include a resin emulsion adhesive, wherein the resin emulsion adhesive can include vinyl acetate resin, acrylic ester copolymer, vinyl acetate/diocyl maleate copolymer, acrylic copolymer, or any combination thereof.
Other suitable pressure sensitive adhesives 14 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein.
The pressure sensitive adhesive 14 can be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the pressure sensitive adhesive 14 can be located on the entire surface of
the front side 3 of the backing 2 or the pressure sensitive adhesive 14 can be located on a portion of the surface of the front side 3 of the backing 2. Preferably, the pressure sensitive adhesive 14 can be located on the entire surface of the front side 3 of the backing 2. hi addition to being located on the surface of the front side 3 of the backing 2, the pressure sensitive adhesive 14 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the pressure sensitive adhesive 14 can be partially embedded into the backing 2). As shown in Figure 9, the pressure sensitive adhesive 14 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No.
5,536,263, and references cited therein. For example, the pressure sensitive adhesive 14 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2. As such, the pressure sensitive adhesive 14 can be partially embedded into the backing 2.
Preferably, the pressure sensitive adhesive 14 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the pressure sensitive adhesive 14 is partially embedded into the backing 2). Alternatively, a portion of the front side 3 of the backing 2 can include the pressure sensitive adhesive 14 and other portions of the front side 3 of the backing 2 can include the xanthophylls 15. The pressure sensitive adhesive 14 , being partially embedded into the front side 3 of the backing 2, imparts strength and structure into the adhesive patch 1.
For example, when the pressure sensitive adhesive 14 is partially embedded into the backing 2, the likelihood that the adhesive patch 1 will tear apart when separated from the release liner 10 or when removed from the skin after use, is minimized. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the pressure sensitive adhesives 14 can be in continuous contact with the skin surface of the patient.
Emulsifier
The formulation 5 or pressure sensitive adhesive 14 can optionally include a compound that emulsifies the formulation 5 or the pressure sensitive adhesive 14. One suitable compound that effectively emulsifies the formulation
5 or the pressure sensitive adhesive 14 is pectin. The emulsifier (e.g., pectin) can be present in any suitable amount, provided the suitable amount is effective to emulsify the formulation 5 or the pressure sensitive adhesive 14 and the emulsifier remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Specifically, the emulsifier (e.g., pectin) can be present up to about 30.0 wt.% of the formulation 5, in about 1.0 wt.% to about 20.0 wt.% of the formulation 5, or in about 2.0 wt.% to about 10.0 wt.% of the formulation 5.
Polymer
The pressure sensitive adhesive 14 can optionally include one or more polymers 9. The polymer 9 provides structure and strength to the pressure sensitive adhesive 14 or provides structure and strength to the formulation 5. Any suitable polymer 9 can be employed, provided the polymer 9 provides structure and strength to the pressure sensitive adhesive 14 or provides structure and strength to the formulation 5, and the polymer 9 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
Suitable polymers 9 include natural polymers and synthetic polymers. Specifically, the polymer 9 can include, e.g., karaya, a polyacrylamide, xanthum gum, guar gum, a hydrophilic polymer, a hydrocolloidal polymer, starch, a starch derivative, vinyl acetate copolymer, polyvinyl pyrrolidone, polyethylene oxide, algin, a derivative of algin, a polyacrylate, gelatin, polymaleic acid, polyacrylic acid, polymaleic anhydride, a polyurethane, a polyurea, gum acacia, locust bean gum, modified guar gum, maltodextrin, carboxymethyl cellulose, carboxypropyl cellulose, polyvinyl alcohol, poly AMPS, or a combination thereof. Other suitable polymers 9 are disclosed, e.g., in U.S. Patent No. 4,675,009; U.S. Patent No. 5,536,263; U.S. Patent No. 4,696,854; U.S. Patent No. 5,741,510, and references cited therein. Preferably, the polymer 9 can include polyacrylamide, karaya, or a combination thereof.
Any suitable amount of polymer 9 can be employed, provided the amount of polymer 9 effectively provides structure and strength to the pressure sensitive adhesive 14 or to the formulation 5, and the effective amount of polymer 9 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Typically, the suitable amount of polymer 9 will depend upon the specific polymer 9 employed. Specifically, karaya can be employed as the polymer 9 up to about 60 wt.% of the formulation 5, in about 5.0 wt.% to about 45 wt.% of the formulation 5, or in about 8.0 wt.% to about 40 wt.% of the formulation 5; polyacrylamide can be employed as the polymer 9 up to about 40 wt.% of the formulation 5, in about 5.0 wt.% to about 35 wt.% of the formulation 5, or in about 8.0 wt.% to about 30 wt.% of the formulation 5; or both karaya and polyacrylamide can be employed as the polymer 9, wherein karaya is present in about 5.0 wt.% to about 35 wt.% of the formulation 5 and polyacrylamide is present in about 5.0 wt.% to about 30 wt.% of the formulation 5.
Humectant The formulation 5 can optionally include one or more humectants 17 to provide a moistening effect to the pressure sensitive adhesive 14. The humectant 17 can optionally hydrate the polymer 9. Any suitable humectant 17 can be employed, provided the humectant 17 effectively provides a moistening effect to the pressure sensitive adhesive 14 and the humectant 17 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. One suitable humectant 17 is glycerin. Other suitable humectants 17 include polyhydric alcohols such as ethylene glycol, propylene glycol, Methylene glycol, tetraethylene glycol, sorbitol, and combinations thereof.
Any suitable amount of humectant 17 can be employed, provided the amount of humectant 17 effectively provides a moistening effect to the pressure sensitive adhesive 14 and the amount of humectant 17 effectively remains stable
in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Typically, the suitable amount of humectant 17 will depend upon the specific humectant 17 employed and the specific polymer 9 employed. For example, karaya, polyacrylamide, or a combination thereof can be employed as the polymer 9 and glycerin can be employed as the humectant 17, wherein the glycerin is present in about 25.0 wt.% to about 70.0 wt.% or in about 40.0 wt.% to about 55.0 wt.% of the formulation 5.
Filler
The formulation 5 can optionally include one or more fillers 6. Any suitable filler 6 can be employed. Suitable fillers 6 include malto dextrin, dextrin, 70% sorbitol water, modified starches, depolymerized starches, and methylcellulose. As used herein, "malto dextrin" is a dextrose equivalent, wherein dextrose is D-glucose. Malto dextrin is commercially available as Amaizo Lodex 5 from American Maize-Products (Hammond, IN). Any suitable amount of filler 6 can be employed in the formulation 5. The suitable amount of filler 6 can depend in part upon the specific filler present in the formulation 5. For example, malto dextrin can be present up to about 20.0 wt.% of the formulation 5, or in about 1.0 wt.% to about 10.0 wt.% of the formulation 5.
Skin Protectant or Skin Conditioner
The formulation 5 can optionally include a skin protectant 18 (i.e., topical moisturizer or skin conditioner). Any suitable skin protectant 18 can be employed, provided the skin is effectively protected or moisturized and the skin protectant remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Additionally, it is preferable that the skin conditioner is medicinally acceptable for topical use in humans.
Suitable topical moisturizers 18 include, e.g. calamine, aloe, lanolin, glycerin, Vitamin E, Vitamin E acetate, farnesol, glycyrrhetinic acid, aluminum
hydroxide gel, cocoa butter, propylene glycol, ethylene glycol, Methylene glycol, hard fat, kaolin, mineral oil, petrolatum, topical starch, white petroleum, cod liver oil, shark liver oil, zinc oxide, or any combination thereof. Additional suitable topical moisturizers 18 are disclosed, e.g., in U.S. Patent Nos. 6,096,334; 6,096,033; 5,741,510; 5,536,263; 4,675,009; 4,307,717; 4,274,420; 5,976,565; 5,536,263; and references cited therein.
As used herein, "aluminum hydroxide gel" refers to a suspension containing aluminum oxide (A12O3), mainly in the form of a hydroxide. It is typically obtained by drying the product of interaction in aqueous solution of an aluminum salt with ammonium or sodium carbonate.
As used herein, "cocoa butter" refers to a fatty substance in cocoa beans; a thick oily solid obtained from cocoa beans and used in making chocolate, cosmetics, and suntan oil. Also known as threobroma oil, it lubricates and softens the skin. As used herein, "topical starch" refers to cornstarch.
As used herein, "kaolin" refers to aluminum silicate; powdered and freed from gritty particles by elutriation. Kaolin refers to the name of the locality in China where the substance is found in abundance.
As used herein, "white petroleum" refers to a purified mixture of hydrocarbons obtained from petroleum. A bleached version of yellow soft paraffin, it is used as an emollient and as a base for ointments. It is odorless when rubbed into the skin and not readily absorbed.
As used herein, "mineral oil" refers to the heavy liquid petrolatum; liquid paraffin or petroleum; a mixture of liquid hydrocarbons obtained from petroleum, and is typically used as a vehicle in medicinal preparations.
As used herein, "petrolatum" refers to petroleum jelly; a yellow soft paraffin; a yellowish mixture of the softer members of the paraffin or methane series of hydrocarbons, obtained from petroleum as an intermediate product in the distillation; typically used as a soothing application to burns and abrasions of the skin, and as a base for ointments.
As used herein, "cod liver oil" refers to the partially destearinated fixed oil extracted from the fresh livers of Gadus morrhuae and other species of the family Gadidae, containing Vitamins A and D.
As used herein, "shark liver oil" refers to the oil extracted from the livers of sharks, mainly of the species Hypoprion brevirostris; a rich source of Vitamins A and D.
As used herein, "zinc oxide" refers to ZnO, which is typically used as a protective ointment.
As used herein, "calamine" is a pink powder of zinc oxide and a skin protectant containing about 98% zinc oxide and about 0.5% ferric oxide; "aloe" is the dried latex of leaves of Curaco Aloe (Aloe barbadenis Miller, Aloe vera Linne) or Cape Aloe (Aloe ferox Miller and hybrids), of the family Liliacaea. Aloe is commercially available as Aloe Vera Gel from Terry Laboratories (Melbourne, FL). Aloe Vera Gel is commercially available as Aloe Vera Gel 4OX (20.0 wt.% solution in water), Aloe Vera Gel IX (0.5 wt.% solution in water), Aloe Vera Gel 1OX (5.0 wt.% solution in water), or solid Aloe Vera. The solid Aloe Vera can be dissolved in a carrier, such as water, to the desired concentration. In addition, the commercially available forms of Aloe Vera are optionally available as decolorized Aloe Vera.
As used herein, "Vitamin E" is 3,4-dihydro-2,5,7,8-tetramethyl-2- (4,8,12-trimethyltridecyl)-2H-l-benzoρyran-6-ol; "Vitamin E acetate" is 3,4- dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-l-benzopyran-6-ol acetate; "lanolin" is the fat-like secretion of the sebaceous glands of sheep (i.e., complex mixture of esters and polyesters of 33 high molecular weight alcohols and 36 fatty acids) which is deposited onto the wool fibers; "farnesol" is 3,7,11- trimethyl-2,6,10-dodecatrien-l-ol. Farnesol is commercially available from American Radiolabeled Chemicals (ARC) (St. Louis, MO), and "glycyrrhetinic acid" is a pentacyclic triterpenoid derivative of the beta-amyrin type and is shown below:
Any suitable amount of skin protectant 18 can be employed, provided the suitable amount of skin protectant 18 effectively protects or moisturizes the skin and the effective amount of skin protectant 18 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. Additionally, it is preferable that the amount of skin conditioner employed is medicinally acceptable for topical use in humans.
Specifically, the skin protectant 18 can be present up to about 20.0 wt.%, up to 10.0 wt.%, up to 5.0 wt.%, or up to 2.0 wt.% of the formulation 5. The suitable and effective amount of skin protectant 18 will depend in part upon the specific skin protectant 18 present in the formulation 5. For example, Aloe Vera Gel, 1OX can be present up to about 20.0 wt.% of the formulation 5, up to about 10.0 wt.% of the formulation 5, up to about 5.0 wt.% of the formulation 5, or up to about 1.0 wt.% of the formulation 5. In addition, Vitamin E acetate can be present up to about 10.0 wt.% of the formulation 5, up to about 5.0 wt.% of the formulation 5, up to about 3.0 wt.% of the formulation 5, up to about 2.0 wt.% of the formulation 5, or up to about 1.0 wt.% of the formulation 5. Preferably, the skin conditioner will be present in an amount that is consistent with any State or Federal regulations.
The skin protectant 18 can be located in at least a portion of the front side 3 of the backing 2, on at least a portion of the front side 3 of the backing 2, or on and in at least a portion of the front side 3 of the backing 2. As such, the skin protectant 18 can be located on the entire surface of the front side 3 of the backing 2 or the skin protectant 18 can be located on a portion of the surface of the front side 3 of the backing 2. Preferably, the skin protectant 18 can be located on the entire surface of the front side 3 of the backing 2. In addition to being located on the surface of the front side 3 of the backing 2, the skin protectant 18 can be located in at least a portion of the underlying surface of the front side 3 of the backing 2 (i.e., the skin protectant 18 can be partially embedded into the backing 2). As shown in Figure 9, the skin protectant 18 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the skin protectant 18 can penetrate about one-tenth to about nine-tenths the
thickness of the backing 2, or about one-fourth to about nine-tenths the thickness of the backing 2. As such, the skin protectant 18 can be partially embedded into the backing 2. Preferably, the skin protectant 18 can be located on the entire front side 3 of the backing 2 and partially in the front side 3 of the backing 2 (i.e., the skin protectant 18 is partially embedded into the backing 2).
Alternatively, a portion of the front side 3 of the backing 2 can include the skin protectant 18 and other portions of the front side 3 of the backing 2 can include any combination of the solvent 13, pressure sensitive adhesive 14, and xanthophylls 15. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the skin protectant 18 can be in continuous contact with the skin surface of the patient.
Preservative
The formulation 5 can optionally include a preservative 7 that is useful for preventing bacterial growth, mold growth, fermentation, and/or decomposition. As used herein, "preservative" refers to any substance which prevents bacterial growth, mold growth, fermentation, and/or decomposition. Concise Chemical and Technical Dictionary, 4th enlarged edition, Chemical Publishing Co., Inc., NY, NY p. 939 (1986). Any suitable preservative 7 can be employed, provided the preservative 7 effectively prevents bacterial growth, mold growth, fermentation, and/or decomposition; and the preservative 7 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 2 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1.
Suitable preservatives 7 include, e.g., quat-15, parabens, dichlorobenzyl alcohol, ethylene diamine tetreacetic acid, formaldehyde, gum benzoin, imidazolidinyl urea, phenyl-mercuric acetate, poly aminopropyl biguanide, proply gallate, sorbic acid, cresol, chloroacetamide sodium benzoate, chloromethyl-methylisothiazolinone, chloromethyl-methylisothiazolon, chloromethyl-methylisothiazolinone benzalkonium chloride, an. octylisothiazolinone benzimidazol-compound, chloromethyl- methylisothiazolinone octylisothiazolinone, o-phenylphenol benzisothiazolinone, o-phenylphenol benzisothiazolinone, benzisothiazolinone, an aliphatic amine of
2-thiopyridineoxide, benzoic acid, editic acid, phenolic acid, benzyl alcohol, isopropyl alcohol, benzenethonium chloride, bronopol, cetrimide, chlorohexidine, chlorobutanol, chlorocresol, phenol, phenoxyethanol, phenyl ethyl alcohol, phenylmercuric acetate, phenyhnercuric borate, phenylmercuric nitrate, potassium sorbate, proplyene glycol, sodium benzoate, sodium propionate, thimerosol, and medicinally acceptable salts thereof. Preferably, the preservative is quat-15, which is commercially available from Dow Chemical (Midland Michigan); methyl paraben; ascorbic acid; or a combination thereof. The preservative 7 can be employed in any suitable amount provided the amount of preservative 7 effectively prevents bacterial growth, mold growth, fermentation, and/or decomposition and the effective amount of preservative 7 remains stable in the formulation 5. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced hi the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. The preservative 7 can be present up to about 99.9 wt. % of the formulation 5, up to about 20.0 wt.% of the formulation 5, up to 5.0 wt.% of the formulation 5, or up to 1.5 wt.% of the formulation 5. The amount of preservative 7 present in the formulation 5 will typically depend upon the specific compound or compounds employed as the preservative 7. For example, quat-15 can be employed in about 0.01 wt.% to about 1.5 wt.% of the formulation 5, in about 0.05 wt.% to about 0.15 wt.% of the formulation 5, or in about 0.08 wt.% to about 0.12 wt.% of the formulation 5.
Complexing Agent In one embodiment of the present invention, the formulation 5 can include xanthophylls 15 that is not soluble and/or stable either without a solvent or with the specific solvent 13, in the amount employed. The use of a complexing agent can be employed to modulate (i.e., regulate) the solubility, stability, and/or the volatility of the xanthophylls 15 in the formulation 5. Any suitable complexing agent can be employed, provided the complexing agent effectively solubilizes and/or stabilizes the xanthophylls 15 and the complexing agent remains stable in the formulation 5 over a prolonged period of time. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the
manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1. In addition, any suitable amount of complexing agent can be employed, provided the amount of complexing agent effectively solubilizes and/or stabilizes the xanthophylls 15 and the amount of complexing agent remains stable in the formulation 5 over a prolonged period of time.
Suitable specific complexing agents include, e.g., cyclodextrins. As used herein, a "cyclodextrin" refers to a non-reducing cyclic oligosaccharide with at least 6 anhydro glucose units linked by alpha 1,4 bonds to form a ring. Cyclodextrins are typically produced by the action of the enzyme cyclodextrin glucosyltransferase [CGT-ase] on starch. The most common cyclodextrins include alpha, beta, and gamma cyclodextrins, which have six, seven, or eight, respectively, anhydroglucose units in the ring structure. All of the hydroxyl groups in cyclodextrins are oriented to the outside of the ring while the glucosidic oxygen and two rings of the non-exchangeable hydrogen atoms are directed towards the interior of the cavity. This combination gives cyclodextrins a hydrophobic inner cavity and a hydrophilic exterior. See, e.g., the Cerestar website (http://www.cerestar.com); the Betadexcyclodextrin website (http://www.betadexcyclodextrin.com); and M. L. Bender and M. Komiyama, Cyclodextrin Chemistry, Springer, Berlin, 1978. Cyclodextrins are enzymatically-modified starches formed by the action of the enzyme cyclodextrin glucosyltransferase on starch. They are doughnut- shaped molecules, which can interact with organic molecules to form complexes. It is also possible for some organic molecules and some inorganic salts to associate with the hydroxyl groups of the cyclodextrin. Three cyclodextrins are typically formed, alpha, beta, and gamma cyclodextrin, which contain six, seven, or eight glucose molecules in the ring, respectively. The electron-dense glycosidic oxygen atoms are oriented inward and line the cavity. The hydroxyl groups are directed toward the outside of the ring. These hydrophilic groups interact with the water to give the cyclodextrins their aqueous solubility properties. The hydrogen and glycosidic oxygen atoms lining the cavity give the cyclodextrin molecule its hydrophobic character and its ability to interact with organic molecules to form complexes. Because of the free rotation of the C-6 carbon, this end of the cyclodextrin cavity is narrower than the end with the C-2 and C-3 hydroxyls.
Derivatives of cyclodextrin can be obtained, e.g., by replacing one or more hydroxyl groups with a suitable radical (i.e., pendant group). Suitable pendant groups include, e.g., sulfmyl; sulfonyl; phosphate; (d-C12)alkyl optionally substituted with one or more (e.g., 1, 2, 3, or 4) hydroxy, carboxy, carbonyl, acyl, oxy, oxo; or a combination thereof. Suitable specific pendant groups include methyl, ethyl, hydroxypropyl, carboxymethyl, sulfate, phosphate, and an acrylate. For example, the specific pendant group can include (C1- C12)alkoxy optionally substituted with one or more hydroxy.
Specific suitable derivatives of cyclodextrin include, e.g., alpha- cyclodextrin sulfate, beta-cyclodextrin sulfate, gamma-cyclodextrin sulfate, alpha-hydroxypropyl cyclodextrin, beta-hydroxypropyl cyclodextrin, gamma- hydroxypropyl cyclodextrin, alpha-cyclodextrin phosphate, beta-cyclodextrin phosphate, and gamma-cyclodextrin phosphate.
Cyclodextrins are starches that have been specially modified by the action of an enzyme to make a water-soluble ring-shaped molecule, capable of holding another, oil-like organic substance in its 'cavity'. Because of this unique property, cyclodextrins can be used to carry all kinds of active ingredients (e.g., drugs, fragrances, flavors, and vitamins) in a wide variety of formulations. Increased stability, water solubility, and controlled release are among the many application benefits. Specifically, cyclodextrins have the benefit of encapsulating a substance, thereby providing protection for the substance. This results in increased shelf-life and a reduced loss of degradation or decomposition. Cyclodextrins are themselves soluble in water, and can greatly increase the solubility of highly water insoluble substances, m addition, cyclodextrins can be used to control the release of a substance.
Suitable cyclodextrins include alpha cyclodextrins, beta cyclodextrins, and gamma cyclodextrins. Specifically, the cyclodextrin can be hydroxylpropyl beta cyclodextrin, hydroxylproplyl alpha cyclodextrin, or a combination thereof. In addition, the cyclodextrin can optionally be branched. Suitable cyclodextrins, and derivatives thereof, can be found, e.g., at U.S.
Patent No. 5,376,641; U.S. Patent No.5,229,370; U.S. Patent No.4,383,992; the Cerestar website (http://www.cerestar.com); the Betadexcyclodextrin website (http://www.betadexcyclodextrin.com); French et al., Archives in Biochem. and
Biophysics, Volume III, (1965) 153-150; the carbomer website (http://www.carbomer.com) and references cited therein.
In one embodiment of the present invention, the formulation 5 can further include a penetration enhancer effective to improve the penetration of the xanthophylls into and through bodily tissue (e.g., skin), with respect to a formulation 5 lacking the penetration enhancer. The penetration enhancer may generally be any penetration enhancer. Suitable penetration enhancers include, e.g., diethylene glycol monoethyl ether (transcutol), dimethyl sulfoxide (DMSO), propyleneglycol, ionic surfactants, non-ionic surfactants, anionic surfactants, isopropyl myristate (DPM), calcipotriene, detergents, emollients, chelators (e.g., calcium chelators such as EDTA, EGTA), and combinations thereof. Additional Examples of enhancers include Loramide DEA, Ethoxydiglycol, NMP, Triacetin, Propylene Glycol, Benzyl Alcohol, Sodium Laureth Sulfate, Dimethyl Isosorbide, Isopropyl Myristate, Olive Squalane, Medium Chain Triglyceride Oil (MCT Oil), Menthol, Isopropyl Palmitate, Isopropyl Isostearate, Propylene Glycol Monostearate, Lecithin, Diisopropyl Adipate, Diethyl Sebacate, Oleic Acid, Ethyl Oleate, Urea, Glyceryl Oleate, Caprylic/Capric Triglyceride, Propylene Glycol Dicaprylate/Dicaprate, Laureth -4, Oleth-2, Oleth-20, Propylene Carbonate, Nonoxynol-9, 2-n-nonyl-l,3- dioxolane, C7 to C14-hydrocarbyl substituted 1,3-dioxolane, 1,3-dioxane, or acetal, and Nonoxynol-15. Specifically, the skin absorption enhancer can include diethylene glycol monoethyl ether (transcutol). As used herein, "diethylene glycol monoethyl ether" or "transcutol" refers to 2-(2- ethoxyethoxy)ethanol [CAS NO. 001893]. The penetration enhancer can be present in the formulation 5 in any suitable and appropriate amount (e.g., between about 1 wt.% and about 10 wt.%).
In one embodiment of the present invention, the formulation 5 can further include a keratolytic agent. As used herein, "keratolytic agent" refers to a substance that causes desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis. Any suitable keratolytic agent can be employed, preferably the keratolytic agent effectively causes desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis. Preferably, the keratolytic agent is pharmaceutically acceptable for topical use
on humans. Suitable keratolytic agents include, e.g., alcloxa, resorcinol, or a combination thereof. As used herein, "alcloxa" refers to Al-chlorhydroxy allontoinate; and "resorcinol" refers to m-dihydroxybenzene or 1,3-benzenediol. Any suitable and effective amount of keratolytic agent can be employed, provided the amount of keratolytic agent effectively causes desquamation
(loosening) and debridement or sloughing of the surface cells of the epidermis. The keratolytic agent can include an amount of alkaline material (e.g., potassium hydroxide (KOH), sodium hydroxide (NaOH), etc.), effective to cause desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis. Alternatively, the desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis can be achieved with the use, e.g., of mechanical stripping, tape, etc. Alternatively, the desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis can be achieved with the use, e.g., of radiant energy such as ultrasound, heat, etc., or with the use of photodynamic therapy.
Topical Acne Drug
The formulation 5 can further include a topical acne drug 15, useful to treat acne. The topical acne drug 15 can be present in any appropriate and suitable amount, provided the amount of topical acne drug 15 is effective to treat and/or prevent acne or a pimple and the amount of topical acne drug 15 remains stable in the formulation 5 over a prolonged period of time. Preferably, the stability is over a prolonged period of time, e.g., up to about 3 years, up to about 1 year, or up to about 6 months, typically experienced in the manufacturing, packaging, shipping, and/or storage of the patch 1. Typically, the topical acne drug 15 can be present in about 0.01 wt.% to about 99.9 wt.% of the formulation 5. Specifically, the amount of topical acne drug present in the formulation 5 can be up to about 5.0 wt.% of the formulation 5, up to 4.0 wt.% of the formulation 5, up to 3.0 wt.% of the formulation 5, or in about 0.5 wt.% to about 2.0 wt.% of the formulation 5. Preferably, the topical acne drug 15 and amount thereof will comply with FDA regulations (e.g., 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, April 1, 2000 Edition).
The amount of topical acne drug 15 present in the formulation 5 will typically depend upon the specific compound or compounds employed as the
topical acne drag 15. For example, salicylic acid can be present up to about 99.9 wt.% of the formulation 5, up to about 10.0 wt.% of the formulation 5, up to 2.0 wt.% of the formulation 5, or up to about 2.0 wt.% of the formulation 5. Specifically, resorcinol can be present up to about 2 wt.% of the formulation 5, in accordance with 21 CFR Ch.l, §§ 333.320(a) and 333.310(a). Specifically, resorcinol monoacetate can be present up to about 3 wt.% of the formulation 5, in accordance with 21 CFR Ch.l, §§ 333.320(b) 333.310(b). Specifically, salicylic acid can be present in about 0.5 wt.% to about 2.0 wt.% of the formulation 5, in accordance with 21 CFR Ch.l, § 333.310(c). Specifically, sulfur can be present in about 3.0 wt.% to about 10.0 wt.% of the formulation 5, in accordance with 21 CFR Ch.l, § 333.310(d).
The topical acne drug 15 can preferably be located on and in any portion of the formulation 5, which is located on the front side 3 of the backing 2. Preferably, the topical acne drug 15 can be located on and in the entire portion of the formulation 5. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the topical acne drag 15 can be in continuous contact with the skin surface of the patient.
The topical acne drug 15 can be located on the entire surface of the front side 3 of the backing 2 or the topical acne drag 15 can be located on a portion of the surface of the front side 3 of the backing 2. Preferably, the topical acne drag 15 can be located on the entire front side 3 of the backing 2. In addition to being located on the surface of the front side 3 of the backing 2, the topical acne drag 15 can be located in at least a portion of the front side 3 of the backing 2 (i.e., the topical acne drag 15 can be partially embedded into the backing 2). As shown in Figure 10, the topical acne drag 15 can penetrate a substantial portion of the front side 3 of the backing 2, as disclosed, e.g., in U.S. Patent No. 5,536,263, and references cited therein. For example, the topical acne drag 15 can penetrate about one-tenth to about nine-tenths the thickness of the backing 2, or about one- fourth to about nine-tenths the thickness of the backing 2. As such, the topical acne drag 15 can be partially embedded into the backing 2. When the adhesive skin patch 1 is placed upon the skin of a patient (e.g., human), the topical acne drug 15 can be in continuous contact with the skin surface of the patient.
In one embodiment of the present invention, an adhesive skin patch 1 is provided in which the formulation 5 does not include xanthophylls 15. In such
an embodiment, the adhesive skin patch 1 can be manufactured, shipped, and stored without xanthophylls 15, and an xanthophylls 15 can be introduced to the adhesive skin patch 1 at a later time.
The formulation 5 can preferably remain stable over the period of time typically experienced with the manufacturing, packaging, shipping, and/or storage of the adhesive skin patch 1, e.g., up to about a month, up to about a year, up to about two years, or up to about 3 years. The stability of the xanthophylls 15, for example, is due in part to the formulation 5 including the xanthophylls 15 in an adhesive formulation. The adhesive formulation is preferably a hydrogel that holds the xanthophylls 15 in an available form while maintaining the necessary stability, pressure sensitive adhesion and effectiveness over a prolonged period of time, e.g., up to about a month, up to about a year, up to about two years, or up to about 3 years.
The adhesive skin patch 1 can have any suitable size and shape. In addition, the adhesive skin patch 1 can be cut, as desired, to provide an adhesive skin patch 1 of a desired size and shape. The adhesive skin patch 1 can be cut with any suitable cutting device such as a scissors, scalpel, or knife.
The adhesive skin patch 1 can have any suitable length. In one embodiment of the present invention, the patch can be a self- wound roll 25 without a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. See, e.g., Figure 10. In such an embodiment, the adhesive skin patch 1 can have a length of about 12 inches to about 100 yards, about 10 feet to about 50 yards, or about 20 feet to about 20 yards. Additionally, in such an embodiment, the adhesive skin patch 1 can have a width of about 0.1 inch to about 5.0 inches, about 0.1 inch to about 1.0 inch, or about 0.1 inch to about 0.5 inch.
In one embodiment of the present invention, the adhesive skin patch 1 can be rectangular and can have a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. In such an embodiment, the adhesive skin patch 1 can typically have a length of up to about 10 inches, up to about 6 inches, up to about 4 inches, or up to about 2 inches. The adhesive skin patch 1 can have any suitable width. Typically, the adhesive skin patch 1 will have a width of up to about 5 inches, up to about 2.5 inches, up to about 1 inch, or up to about 0.5 inch. Additionally, the adhesive skin patch 1 can have any suitable
thickness. Typically, the adhesive skin patch 1 will have a thickness of about 0.10 mm to about 2.0 mm, about 0.15 mm to about 1.0 mm, or about 0.20 mm to about 0.75 mm.
In one specific embodiment of the present invention, the adhesive skin patch 1 can be crescent, oval or circular in shape. The circular adhesive skin patch 1 can have a diameter of about 0.1 inch to about 10 inches. Preferably, the circular adhesive skin patch 1 can have a diameter of about 1.5 inches to about 5 inches. See, Fig. 7.
In another specific embodiment of the present invention, the adhesive skin patch 1 can be rectangular in shape. The rectangular adhesive skin patch 1 can have a length of about 1 inch to about 10 inches and a width of about 1 inch to about 10 inches. Preferably, the rectangular adhesive skin patch 1 can have a length of about 1 inch to about 2 inches and a width of about 0.1 inch to about 0.75 inch. See, Fig. 8. In one embodiment of the present invention, the adhesive skin patch 1 can have a release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. In such an embodiment, one or more adhesive skin patches 1 can be mounted on the release liner 10. For example, one adhesive skin patch 1 can have one release liner 10 mounted on the front side 3 of the backing 2 of the adhesive skin patch 1. Alternatively, about 2 to about 100 or about 2 to about 20 adhesive skin patches 1 can be mounted on the release liner 10. The cost of having two or more patches 1 on a single release liner 10 is typically less expensive than skin patches 1 that are separately mounted on a single release liner 10. In addition, some consumers may prefer the ease and comfort of carrying a single patch assembly that includes a single release liner 10 and more than one (e.g., about 2 to about 20, or about 2 to about 10) adhesive patches 1 mounted on the single release liner 10.
The adhesive skin patch 1 can be applied to any suitable skin surface of the patient. For example, when the adhesive skin patch 1 is used to treat topical skin disorders (e.g., wrinkles, acne, etc.), the adhesive skin patch 1 can be applied to that surface of the skin that is afflicted with the topical skin disorder. In such an embodiment, the adhesive skin patch 1 can locally deliver a cosmetically and/or therapeutically effecteive amount of xanthophylls 15.
Alternatively, when the adhesive skin patch 1 is used to treat other disorders (e.g., macular degeneration, angiogenesis, cancer, heart disease, and diabetes), the adhesive skin patch 1 can be applied to any topical skin surface, for systemic delivery of the xanthophylls 15.
The adhesive patch 1 of the present invention can be formulated or manufactured employing the above components. The adhesive patch 1 of the present invention can be formulated or manufactured using any suitable technique. Preferably, the adhesive patch 1 can be formulated or manufactured as described herein or as described in U.S. Patent No. 5,536,263; U.S. Patent No. 5,741,510; and references cited therein; wherein the backing can be treated with a sizing agent 8 prior to the infusion of the formulation 5.
The invention can be illustrated by the following non-limiting examples.
Examples
Example 1
Example 2
Example 3
Example 4
Example 5
Example 6
Example 7
Example 8
Example 9
Example 10
Example 11
Example 12
Example 13
Example 14
Example 15
Example 16
All publications, patents, and patent documents cited herein are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.
Claims
1. An adhesive patch comprising a flexible backing having a front side and a back side and a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing; wherein the formulation comprises: xanthophylls; a solvent that dissolves the xanthophylls; and a pressure sensitive adhesive.
2. The adhesive patch of claim 1 , wherein the xanthophylls comprise lutein, zeaxanthin, capsorubin, capsanthin, astaxanthin, canthaxanthin, or any combination thereof.
3. The adhesive patch of claim 1, wherein the xanthophylls comprise lutein and zeaxanthin.
4. The adhesive patch of claim 1 , wherein the xanthophylls comprise lutein and zeaxanthin, wherein the lutein is provided in the non-esterified form.
5. The adhesive patch of claim 1, wherein the xanthophylls comprise lutein and zeaxanthin, wherein the lutein is provided as trans-lutein.
6. The adhesive patch of claim 1, wherein the xanthophylls comprise lutein and zeaxanthin, wherein the lutein is provided as trans-lutein that is at least about 50 wt. % pure.
7. The adhesive patch of claim 1, wherein the xanthophylls comprise lutein and zeaxanthin, wherein the lutein is provided as trans-lutein that is about 50 wt.% to about 90 wt.% pure.
8. The adhesive patch of any one of claims 1-7, wherein the formulation is partially embedded in at least a portion of the front side of the backing.
9. The adhesive patch of any one of claims 1-8, wherein the formulation is located on the entire surface of the front side of the backing.
10. The adhesive patch of any one of claims 1 -9, wherein the backing is porous.
11. The adhesive patch of any one of claims 1-9, wherein the backing is non- porous.
12. The adhesive patch of any one of claims 1-9, wherein the backing is vapor permeable.
13. The adhesive patch of any one of claims 1-9, wherein the backing is vapor impermeable.
14. The adhesive patch of any one of claims 1-13, wherein the backing comprises water insoluble material.
15. The adhesive patch of any one of claims 1-13, wherein the backing has a thickness of about 0.025 mm to about 1.25 mm.
16. The adhesive patch of any one of claims 1-15, wherein the backing comprises a nonwoven fabric.
17. The adhesive patch of any one of claims 1-16, wherein the backing comprises polycellulose fibers, polyester fibers, polyurethane fibers, polyolefin fibers, polyamide fibers, cotton fibers, copolyester fibers, or any mixture thereof.
18. The adhesive patch of any one of claims 1-17, wherein upon contact with skin, the backing retains the formulation and the patch allows moisture from the skin to pass.
19. The adhesive patch of any one of claims 1-17, wherein upon contact with skin, the backing retains the formulation and the patch does not allows moisture from the skin to pass.
20. The adhesive patch of any one of claims 1-19, wherein the solvent comprises a polyhydric alcohol, water, or a combination thereof.
21. The adhesive patch of claim 20, wherein the polyhydric alcohol is propylene glycol, ethylene glycol, or a combination thereof.
22. The adhesive patch of claim 21 , wherein the propylene glycol is present in about 3.0 wt.% to about 11.0 wt.% of the formulation.
23. The adhesive patch of claim 20, wherein the water is present in about 2.0 wt.% to about 20.0 wt.% of the formulation.
24. The adhesive patch of any one of claims 1 -23 , wherein the solvent is present in about 6.0 wt.% to about 24.0 wt.% of the formulation.
25. The adhesive patch of any one of claims 1 -24, wherein the formulation further comprises a filler.
26. The adhesive patch of claim 25, wherein the filler is malto dextrin.
27. The adhesive patch of claim 26, wherein the malto dextrin is present in about 1.0 wt.% to about 10.0 wt.% of the formulation.
28. The adhesive patch of any one of claims 1-27, wherein the pressure sensitive adhesive comprises one or more acrylic ester copolymers.
29. The adhesive patch of claim 28, wherein the one or more acrylic ester copolymers are present in about 3.0 wt.% to about 20.0 wt.% of the formulation.
30. The adhesive patch of claim 28, wherein the acrylic ester copolymer is present in about 5.0 wt.% to about 15.0 wt.% of the formulation.
31. The adhesive patch of any one of claims 1-30, wherein the adhesive is positioned on the entire front side of the backing.
32. The adhesive patch of any one of claims 1-30, wherein the adhesive is positioned on a portion of front side of the backing.
33. The adhesive patch of any one of claims 1-30, wherein the adhesive is partially embedded in at least a portion of the backing.
34. The adhesive patch of any one of claims 1-33, wherein the pressure sensitive adhesive further comprises glycerin.
35. The adhesive patch of claim 34, wherein the glycerin is present in about 25.0 wt.% to about 70.0 wt.% of the formulation.
36. The adhesive patch of claim 34, wherein the glycerin is present in about 45.0 wt.% to about 55.0 wt.% of the formulation.
37. The adhesive patch of any one of claims 1-36, wherein the pressure sensitive adhesive comprises an emulsifier.
38. The adhesive patch of claim 37, wherein the emulsifier is pectin.
39. The adhesive patch of claim 38, wherein the pectin is present in about 2.0 wt.% to about 10.0 wt.% of the formulation.
40. The adhesive patch of any one of claims 1-30, wherein the pressure sensitive adhesive comprises a compound that provides structure and strength to the pressure sensitive adhesive or to the formulation.
41. The adhesive patch of claim 40, wherein the compound that provides structure and strength to the pressure sensitive adhesive or to the formulation is karaya, a polyacrylamide, xanthum gum, guar gum, a natural polymer, a synthetic polymer, a hydrophilic polymer, a hydrocolloidal polymer, starch, a starch derivative, vinyl acetate copolymer, polyvinyl pyrrolidone, polyethylene oxide, algin, derivatives of algin, a polyacrylate, polymaleic acid, polymaleic anhydride, a polyurethane, a polyurea, gum acacia, locust bean gum, modified guar gum, maltodextrin, carboxymethyl cellulose, carboxypropyl cellulose, polyvinyl alcohol, poly AMPS or a mixture thereof.
42. The adhesive patch of claim 40, wherein the compound that provides structure and strength to the pressure sensitive adhesive or to the formulation is polyacrylamide.
43. The adhesive patch of claim 42, wherein the polyacrylamide is present in about 8.0 wt.% to about 30.0 wt.% of the formulation.
44. The adhesive patch of claim 40, wherein the compound that provides structure and strength to the pressure sensitive adhesive or to the formulation is karaya.
45. The adhesive patch of claim 44, wherein the karaya is present in about 8.0 wt.% to about 40.0 wt.% of the formulation.
46. The adhesive patch of claim 40, wherein the compound that provides structure and strength to the pressure sensitive adhesive or to the formulation is a combination of polyacrylamide and karaya.
47. The adhesive patch of any one of claims 1 -46, wherein the pressure sensitive adhesive is located on the entire portion of the front side of the backing.
48. The adhesive patch of any one of claims 1-47, wherein the formulation further comprises a skin conditioner.
49. The adhesive patch of claim 48, wherein the skin conditioner is calamine, aloe, lanolin, glycerin, Vitamin E, Vitamin E acetate, farnesol, glycyrrhetinic acid, or any combination thereof.
50. The adhesive patch of claim 49, wherein the aloe is present in about 0.01 wt. % to about 2.0 wt.% of the formulation.
51. The adhesive patch of claim 49, wherein the Vitamin E acetate is present in about 0.01 wt.% to about 2.0 wt.% of the formulation.
52. The adhesive patch of any one of claims 1-51, wherein the formulation further comprises Vitamin A.
53. The adhesive patch of claim 49, wherein the Vitamin A is present in about 0.01 wt.% to about 2.0 wt.% of the formulation.
54. The adhesive patch of any one of claims 1-53, wherein the formulation further comprises one or more antimicrobial agents.
55. The adhesive patch of claim 54, wherein the antimicrobial agent is a β- lactam compound, an aminoglycoside, or an antifungal agent.
56. The adhesive patch of claim 54, wherein the antimicrobial agent is erythromycin, tetracycline, clindamycin, or cephalosporin.
57. The adhesive patch of any one of claims 1-56, wherein the formulation further comprises one or more antiseptic agents.
58. The adhesive patch of claim 57, wherein the antiseptic agent is triclosan, phenoxy isopropanol, chlorhexidine gluconate, povidone iodine, or any combination thereof.
59. The adhesive patch of any one of claims 1-58, having a thickness of about 0.20 mm to about 0.75 mm.
60. The adhesive patch of any one of claims 1 -59, further comprising a release liner that is mounted on the front side of the backing.
61. The adhesive patch of claim 60, wherein more than one patch is mounted on the release liner.
62. The adhesive patch of claim 61, wherein about 2 to about 20 adhesive patches are mounted on the release liner.
63. The adhesive patch of any one of claims 1-62, that is crescent, circular, or oval.
64. The adhesive patch of claim 63, having a diameter of about 0.1 inch to about 1.0 inch.
65. The adhesive patch of any one of claims 1 -64, further comprising a topical acne drug.
66. The adhesive patch of claim 65, wherein the topical acne drug is salicylic acid, resorcinol, resorcinol acetate, benzoyl peroxide, sulfur, retinol, retinoic acid, citric acid, an alpha hydroxy acid, retinal, a pharmaceutically acceptable salt thereof, or any combination thereof.
67. The adhesive patch of any one of claims 1 -66, wherein the topical acne drug is salicylic acid or a pharmaceutically acceptable salt thereof.
68. The adhesive patch of claim 67, wherein the salicylic acid or the pharmaceutically acceptable salt thereof is present in about 0.5 wt.% to about 2.0 wt.% of the formulation.
69. The adhesive patch of claim 66, wherein the sulfur is present in about 3.0 wt.% to about 10.0 wt.% of the formulation.
70. The adhesive patch of any one of claims 1-69, wherein at least a portion of the backing is treated with a hydrophobic sizing agent such that the portion of the backing that is treated with the hydrophobic sizing agent has a surface energy of about 20 dynes/cni2 to about 65 dynes/cni2
71. The adhesive patch of claim 70, wherein the hydrophobic sizing agent is a fluorocarbon solution, a silicone-containing compound, or a combination thereof.
72. The adhesive patch of claim 70, wherein the backing that is treated with the fluorocarbon solution is Vilmed M1585 W/HY, Vilmed M1585H/HY, Vilmed M1586 W/HY, Vilmed M1586 H/HY, Vilmed M1570, Vilmed M1573 F, Vilmed M1573 FH, Vilmed M1577 F, Vilmed M1578 F, Vilmed M1578 FH, or a combination thereof.
73. The adhesive patch of claim 70, wherein the silicone-containing compound is a polydimethyl siloxane, a dialkylsiloxane, a dimethylsiloxo vinyl alkene, a dialkylsiloxo vinyl alkene, a dimethylsiloxo acrylate, a dialkylsiloxo acrylate, a vinyl terminated polydimethylsiloxane, a vinyl terminated polydialkylsiloxane, or a combination thereof.
74. The adhesive patch of claim 70, wherein at least a portion of the front side of the backing is treated with the sizing agent.
75. The adhesive patch of claim 70, wherein the entire surface of the front side of the backing is treated with the sizing agent.
76. The adhesive patch of claim 70, wherein the entire backing is treated with the sizing agent.
77. The adhesive patch of claim 70, wherein the sizing agent is partially embedded in the backing.
78. The adhesive patch of claim 70, wherein the portion of the backing treated with the hydrophobic sizing agent has a surface energy of about 27 dynes/cni2 to about 56 dynes/cni2.
79. The adhesive patch of claim 70, wherein the entire surface of the backing is treated with the hydrophobic sizing agent.
80. The adhesive patch of claim 70, wherein the hydrophobic sizing agent penetrates at least a portion of the underlying surface of the backing.
81. The adhesive patch of claim 70, wherein the hydrophobic sizing agent penetrates the entire underlying surface of the backing.
82. The adhesive patch of any one of claims 1-81, further comprising a penetration enhancer.
83. The adhesive skin patch of claim 82, wherein the penetration enhancer comprises diethylene glycol monoethyl ether (transcutol), dimethyl sulfoxide (DMSO), propyleneglycol, ionic surfactants, non-ionic surfactants, anionic surfactants, isopropyl myristate (IPM), calcipotriene, detergents, emollients, chelators (e.g., calcium chelators such as EDTA, EGTA), Loramide DEA, Ethoxydiglycol, NMP, Triacetin, Propylene Glycol, Benzyl Alcohol, Sodium Laureth Sulfate, Dimethyl Isosorbide, Isopropyl Myristate, Olive Squalane, Medium Chain Triglyceride Oil (MCT Oil), Menthol, Isopropyl Palmitate, Isopropyl Isostearate, Propylene Glycol Monostearate, Lecithin, Diisopropyl Adipate, Diethyl Sebacate, Oleic Acid, Ethyl Oleate, Urea, Glyceryl Oleate, Caprylic/Capric Triglyceride, Propylene Glycol Dicaprylate/Dicaprate, Laureth -4, Oleth -2, Oleth-20, Propylene Carbonate, Nonoxynol-9, 2-n-nonyl-l,3- dioxolane, C7 to C14-hydrocarbyl substituted 1,3-dioxolane, 1,3-dioxane, or acetal, and Nonoxynol- 15.
84. The adhesive skin patch of claim 82, wherein the penetration enhancer is present in the formulation in about 0.1 wt.% to about 20.0 wt.%
85. The adhesive patch of any one of claims 1 -84, further comprising a keratolytic agent.
86. The adhesive skin patch of claim 85, wherein the keratolytic agent comprises alcloxa, resorcinol, or a combination thereof.
87. The adhesive skin patch of claim 85, wherein the keratolytic agent is present in the formulation in about 0.1 wt.% to about 5.0 wt.%
88. The adhesive patch of any one of claims 1-87, further comprising Vitamin A, all-trans retinoic acid, or a combination thereof.
89. An adhesive patch comprising a flexible backing having a front side and a back side and a formulation positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing; wherein the formulation comprises: xanthophylls; and a hot melt adhesive.
90. A method of locally delivering xanthophylls to a topical skin surface, the method comprising topically applying to a skin surface an adhesive patch of any one of claims 1-89, for a period of time effective to locally deliver xanthophylls to the topical skin surface.
91. A method of systemically delivering xanthophylls to a mammal, the method comprising topically applying to a skin surface an adhesive patch of any one of claims 1-89, for a period of time effective to systemically deliver xanthophylls to the mammal.
92. A method for treating or preventing acne or a pimple in a mammal in need thereof comprising applying to the skin surface of the mammal having the acne or the pimple or the skin surface of the mammal at risk thereof an adhesive patch of any one of claims 1-89, for an effective period of time to effectively treat or prevent acne or a pimple.
93. The method of claim 92, wherein the mammal is a human.
94. The method of claim 92, wherein the skin surface of the mammal having the acne or pimple or the skin surface of the mammal at risk thereof is the face, neck, shoulder, chest, back, or any combination thereof.
95. The method of claim 92, wherein the period of time is about one hour to about 12 hours.
96. A method for exfoliating the skin surface of a mammal, the method comprising applying to the skin surface of the mammal in need of such exfoliating an adhesive patch of any one of claims 1-89, for an effective period of time and removing the adhesive patch, thereby effectively exfoliating the skin surface.
97. The method of claim 96, wherein the mammal is a human.
98. The method of claim 96, wherein the effective period of time is about one second to about 12 hours.
99. A method for improving the appearance of skin surface in a mammal, the method comprising applying to the skin surface of the mammal in need of such appearance improvement, the adhesive patch of any one of claims 1-89, for an effective period of time to effectively improve the appearance of the skin surface.
100. The method of claim 99 wherein the mammal is a human.
101. An adhesive patch of any one of claims 1-89, for use in medical therapy.
102. The use of an adhesive patch of any one of claims 1-89, for the manufacture of a medicament for treating a topical skin condition.
103. The use of an adhesive patch of any one of claims 1 -89, for the manufacture of a medicament for treating acne in a mammal, treating pimples in a mammal, improving the appearance of skin surface of a mammal, or any combination thereof.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US62992704P | 2004-11-22 | 2004-11-22 | |
PCT/US2005/042418 WO2006062740A2 (en) | 2004-11-22 | 2005-11-22 | Topical skin patch containing xanthophylls |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1827400A2 true EP1827400A2 (en) | 2007-09-05 |
Family
ID=36273361
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP05852052A Withdrawn EP1827400A2 (en) | 2004-11-22 | 2005-11-22 | Topical skin patch containing xanthophylls |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1827400A2 (en) |
JP (1) | JP2008520735A (en) |
CA (1) | CA2588905A1 (en) |
WO (1) | WO2006062740A2 (en) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2201930A1 (en) * | 2008-12-23 | 2010-06-30 | Intendis GmbH | Hydrogel composition for the treatment of dermatological disorders |
EP2316438A1 (en) * | 2009-10-30 | 2011-05-04 | Johnson & Johnson GmbH | Tape , in particular adhesive tape, for the treatment of skin disorders comprising at least one hyperkeratosis inhibitor and/or at least one keratinolytic agent |
JP2012092022A (en) * | 2010-10-25 | 2012-05-17 | Tokuhon Corp | External skin patch |
CN102824289A (en) * | 2012-09-18 | 2012-12-19 | 铜陵洁雅生物科技股份有限公司 | Oil control and acne removal wet tissue |
EP3113849B1 (en) * | 2014-02-26 | 2019-06-12 | Luma Therapeutics, Inc. | Ultraviolet phototherapy apparatus |
WO2016065008A1 (en) | 2014-10-21 | 2016-04-28 | The Procter & Gamble Company | Method of improving skin appearance |
EP3365067B1 (en) | 2015-10-22 | 2019-11-20 | The Procter and Gamble Company | Barrier patch of a foamed film and methods of improving skin appearance |
CN108136230B (en) | 2015-10-22 | 2022-05-13 | 宝洁公司 | Barrier patches for foamed films and methods of improving the appearance of skin |
JP6960937B2 (en) | 2016-03-08 | 2021-11-05 | リビング プルーフ インコーポレイテッド | Long-lasting cosmetic composition |
KR101816169B1 (en) | 2016-07-11 | 2018-01-09 | 광주과학기술원 | Artifical skin dyed with pigment, method of dyeing artifical skin |
US10751265B2 (en) | 2017-01-09 | 2020-08-25 | The Procter & Gamble | Barrier patch with soluble film and methods of improving skin appearance |
US10857076B2 (en) | 2017-01-09 | 2020-12-08 | The Procter & Gamble Company | Barrier patch with soluble film and methods of improving skin appearance |
WO2018129495A1 (en) | 2017-01-09 | 2018-07-12 | The Procter & Gamble Company | Barrier patch with soluble film and methods of improving skin appearance |
US10959918B2 (en) | 2017-06-22 | 2021-03-30 | The Procter & Gamble Company | Films including a water-soluble layer and a vapor-deposited coating |
JP7244495B2 (en) | 2017-09-13 | 2023-03-22 | リビング プルーフ インコーポレイテッド | Long lasting cosmetic composition |
US10842729B2 (en) | 2017-09-13 | 2020-11-24 | Living Proof, Inc. | Color protectant compositions |
CA3084488A1 (en) | 2017-11-20 | 2019-05-23 | Living Proof, Inc. | Properties for achieving long-lasting cosmetic performance |
CN111698984B (en) | 2018-03-19 | 2023-11-14 | 宝洁公司 | Method for preparing barrier patch with soluble film |
CN108841166A (en) * | 2018-07-11 | 2018-11-20 | 安徽嘉明新材料科技有限公司 | A kind of degradable TPU packaging film |
TWI683676B (en) * | 2018-12-25 | 2020-02-01 | 寶齡富錦生技股份有限公司 | Antimicrobial kit and article |
KR102656495B1 (en) * | 2023-11-29 | 2024-04-12 | 주식회사 제브 | Sports patch and Sports patch manufacturing equipment |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0925209A (en) * | 1995-07-14 | 1997-01-28 | Shiseido Co Ltd | Skin preparation for external use |
WO2000016752A2 (en) * | 1998-09-18 | 2000-03-30 | Lavipharm Laboratories, Inc. | Transdermal devices comprising essential oils for aromatherapy |
DE19856432A1 (en) * | 1998-12-08 | 2000-06-15 | Basf Ag | Nanoparticulate core-shell systems and their use in pharmaceutical and cosmetic preparations |
JP4070935B2 (en) * | 2000-03-31 | 2008-04-02 | 株式会社コーセー | Acne skin external preparation |
US20040071757A1 (en) * | 2001-11-20 | 2004-04-15 | David Rolf | Inhalation antiviral patch |
FR2832926B1 (en) * | 2001-11-30 | 2004-02-27 | Oreal | COSMETIC OR DERMATOLOGICAL COMPOSITION COMPRISING A RETINOIDE AND / OR A CAROTENOID AND ACEXAMIC ACID |
US20030133960A1 (en) * | 2001-11-30 | 2003-07-17 | L'oreal | Cosmetic and dermatological uses of a retinoid and/or a carotenoid and acexamic acid |
US20040156873A1 (en) * | 2003-02-10 | 2004-08-12 | Gupta Shyam K. | Topically Bioavailable Acne and Rosacea Treatment Compositions |
-
2005
- 2005-11-22 CA CA002588905A patent/CA2588905A1/en not_active Abandoned
- 2005-11-22 WO PCT/US2005/042418 patent/WO2006062740A2/en active Application Filing
- 2005-11-22 EP EP05852052A patent/EP1827400A2/en not_active Withdrawn
- 2005-11-22 JP JP2007543428A patent/JP2008520735A/en active Pending
Non-Patent Citations (1)
Title |
---|
See references of WO2006062740A2 * |
Also Published As
Publication number | Publication date |
---|---|
WO2006062740A3 (en) | 2006-08-10 |
CA2588905A1 (en) | 2006-06-15 |
WO2006062740A2 (en) | 2006-06-15 |
JP2008520735A (en) | 2008-06-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2006062740A2 (en) | Topical skin patch containing xanthophylls | |
US20060122282A1 (en) | Method for treating skin disorders with xanthophylls | |
AU2006326388B2 (en) | Compositions and methods for treating dermatological conditions | |
US20060134226A1 (en) | Compositions useful to treat ocular neovascular diseases and macular degeneration | |
KR20080059143A (en) | Topical skin treating compositions | |
US11116714B2 (en) | Systems and methods for treating and/or preventing acne | |
US20050137164A1 (en) | Diclofenac compositions for the treatment of skin disorders | |
JPH02295927A (en) | Method for treating ordinary acne locally | |
JP2008502645A (en) | Spray composition comprising a combination of a corticoid and a vitamin D derivative in an oily phase | |
JP2008539236A (en) | Use of clobetasol spray formulation to treat psoriasis | |
KR20130020742A (en) | Hair follicle targeting compositions | |
KR20110074513A (en) | Topical treatment of skin infection | |
US8409628B2 (en) | Methods and compositions for oxygenation of skin to treat skin disorders | |
JP2015530380A (en) | Composition for treating psoriasis | |
K Akomeah | Topical dermatological drug delivery: quo vadis? | |
US20100068284A1 (en) | Stable Fixed Dose Topical Formulation | |
WO2002024154A2 (en) | Method for topical treatment of anthralin-responsive dermatological disorders | |
Mishra et al. | Topical antibiotics and semisolid dosage forms | |
EP1594456B1 (en) | Use of a composition comprising vitamin k1 oxide or a derivative thereof for the treatment and/or the prevention of mammal dermatological lesions | |
US8900601B2 (en) | Permeable mixtures, methods and compositions for the skin | |
JP2007332055A (en) | External preparation for skin | |
JP2001163783A (en) | Agent for external use for treating dermatosis | |
JP3538367B2 (en) | External preparation for treatment / prevention / improvement of skin tissue disorders | |
CA2963110A1 (en) | Method of administration of chromium and magnesium sulfate for treatment of acne | |
JP2001163782A (en) | Agent for external use for treating dermatosis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20070614 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR |
|
17Q | First examination report despatched |
Effective date: 20071213 |
|
DAX | Request for extension of the european patent (deleted) | ||
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20080624 |