US20120295914A1 - Combination of adrenergic receptor agonist alpha-1 or alpha-2, preferably brimonidine with fillers, preferably hyaluronic acid - Google Patents

Combination of adrenergic receptor agonist alpha-1 or alpha-2, preferably brimonidine with fillers, preferably hyaluronic acid Download PDF

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US20120295914A1
US20120295914A1 US13/322,245 US201013322245A US2012295914A1 US 20120295914 A1 US20120295914 A1 US 20120295914A1 US 201013322245 A US201013322245 A US 201013322245A US 2012295914 A1 US2012295914 A1 US 2012295914A1
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adrenergic receptor
receptor agonist
combination
fillers
brimonidine
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Christophe VILLARD
Sylviane Villard
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Galderma Research and Development SNC
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Galderma Research and Development SNC
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    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
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    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
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    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/06—Flowable or injectable implant compositions

Definitions

  • the present invention is in the surgical and dermatological domain.
  • the present invention provides a combination of quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, and preferably product known as brimonidine with fillers and preferably with hyaluronic acid for decreasing skin or cutaneous reactions.
  • More significant bruising occurs with surgical procedures such as liposuction, breast augmentations/lifts, face lifts and tummy tucks.
  • the present invention is based on the demonstration by the Applicant that the topical application/administration of an adrenergic receptor agonist together with aesthetic or surgical procedure, for instance filler injection, reduces the occurrence of skin/cutaneous reactions.
  • the present invention provides a combination either an association of quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, and preferably product known as brimonidine with fillers and preferably with hyaluronic acid. Said combination is topically administrated to an individual in need.
  • the present invention provides the use in an individual in need, of a quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, and preferably product known as brimonidine in combination or association with fillers and preferably with hyaluronic acid. More specifically, the invention provides the use in an individual in need, of a quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, in combination or association with fillers intended for decreasing of alleviating cutaneous reactions.
  • the quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, in combination or association with fillers are intended to be applied to the skin simultaneously or one after the other, in any order, or in a sequential order and more specifically the skin application of a quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, in combination or association with fillers is within a time interval of less than 1 hour, preferably less than 30 minutes, preferably less than 15 minutes, more preferably less than 5 minutes.
  • the adrenergic receptor agonist ⁇ -1 or ⁇ -2 is brimonidine combination or association with filler(s) or the filler(s) in combination or association with adrenergic receptor agonist ⁇ -1 or ⁇ -2 and preferably brimonidine, is hyaluronic acid.
  • the cutaneous reactions are selected from the following: bruising, bleeding, ecchymosis, erythema, oedema, necrosis, ulceration, swelling and/or inflammation.
  • the present invention provides a kit of part combining or associating a quantity of adrenergic receptor antagonist ⁇ -1 or ⁇ -2, and preferably product known as brimonidine with fillers and preferably with hyaluronic acid.
  • Said quantity of adrenergic receptor antagonist ⁇ -1 or ⁇ -2 is in a form of a topical composition or formulation.
  • the invention provides also a method for diminishing or decreasing or avoid bruising and, to a lesser extent, bleeding and particularly in aesthetic procedures, including dermal fillers and preferably hyaluronic acid, Botulinum toxin and laser resurfacing, by providing to an individual in need thereof a quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, and preferably product known as brimonidine.
  • the invention provides a method for alleviating or decreasing cutaneous reactions and particularly in aesthetic procedures, including injection of dermal fillers and preferably hyaluronic acid, Botulinum toxin and laser resurfacing, by providing to an individual in need thereof a quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, and preferably product known as brimonidine.
  • the cutaneous reactions are selected from the following: bruising, bleeding, ecchymosis, erythema, oedema, necrosis, ulceration, swelling and/or inflammation.
  • association of adrenergic receptor antagonist or salts thereof with fillers means that the two active principles are formulated separately; or adrenergic receptor antagonist (preferably brimonidine) or the salts thereof is thus present in a first composition, while the fillers (preferably hyaluronic acid) is/are present in a second composition.
  • adrenergic receptor antagonist preferably brimonidine
  • the fillers preferably hyaluronic acid
  • the pharmaceutical composition is in the form of a composition A comprising adrenergic receptor antagonist, intended to be applied concomitantly with a composition B comprising the filler(s).
  • composition A and composition B are presented in the form of a kit, allowing concomitant administration of the two compositions, or alternatively in the form of a kit combining in the same presentation at least the two products (compositions A and B) in two separate packages, preferably in the form of tubes (co-packaging).
  • compositions are intended to be applied to the skin simultaneously or one after the other, in any order, or in a sequential order (for example, in which the application of a pharmaceutical composition B comprising precedes the application of the pharmaceutical composition A), but within a time interval of less than 1 hour, preferably less than 30 minutes, preferably less than 15 minutes, more preferably less than 5 minutes or even less than 1 minute.
  • the present invention provides a method for diminishing or decreasing or avoiding bruising and, to a lesser extent, bleeding and particularly in aesthetic procedures, including dermal fillers and preferably hyaluronic acid, Botulinum toxins and laser resurfacing, by providing to an individual in need thereof a quantity of adrenergic receptor agonist ⁇ -1 or ⁇ -2, and preferably product known as brimonidine.
  • adrenergic receptors encompass both ⁇ and ⁇ receptors.
  • ⁇ also noted a-
  • adrenoreceptors ⁇ 1 and ⁇ 2 receptors were distinguished in the 1970's.
  • ⁇ 2 receptors were found to occur on vascular smooth muscles and exhibit mediation of vasoconstrictor response (“Subtypes of functional ⁇ 1 - and ⁇ 2 -adrenoceptors” J R Certy; European Journal of Pharmacology 361 (1998) 1-15).
  • vasoconstrictor response Subtypes of functional ⁇ 1 - and ⁇ 2 -adrenoceptors
  • the agonist can be an agonist of both ⁇ 1 and ⁇ 2 receptors, or can be specific for ⁇ 1 or ⁇ 2.
  • the chosen molecule displays more affinity for the ⁇ 2 than for the ⁇ 1 receptor, and will generally be named, in the rest of the application, “an ⁇ 2 adrenergic receptor agonist”
  • Agonists of the a-2 adrenoceptors have been used therapeutically for a number of conditions including hypertension, congestive heart failure, angina pectoris, spasticity, glaucoma, diarrhea, and for the suppression of opiate withdrawal symptoms (J. P. Heible and R. R. Ruffolo Therapeutic Applications of Agents Interacting with a-Adrenoceptors, p. 180-206 in Progress in Basic and Clinical Pharmacology Vol. 8, P. Lomax and E. S. Vesell Ed., Karger, 1991).
  • Adrenoceptor agonists such as clonidine have been primarily used orally, though a patch formulation is known.
  • a-2 agonists are known to mediate vasoconstriction both in the core and periphery of a patient.
  • a-2 adrenoceptor agonists are known to cause vasoconstriction of peripheral arterioles, in response to stimulation due to cold or stress.
  • the most preferred compound is (5-Bromo-quinoxalin-6-yl)-(4,5-dihydro-1H-imidazol-2-yl)-amine (commonly referred to as brimonidine) and pharmaceutically acceptable salts thereof, particularly the tartrate salt.
  • Other compounds of the invention include naphazoline, tetra-hydrozaline, oxymetazoline, xylometazoline, epinephrine, norepinephrine, phenylephrine and methoxamine and their pharmaceutically acceptable salts.
  • the compounds of the invention are administrated to a patient in need thereof topically. Therefore, in the context of the instant invention the compounds are delivered to the affected area of the skin in a pharmaceutically acceptable topical carrier.
  • a pharmaceutically acceptable topical carrier is any pharmaceutically acceptable formulation that can be applied to the skin surface for topical, dermal, intradermal, or transdermal delivery of a pharmaceutical or medicament.
  • the combination of a pharmaceutically acceptable topical carrier and a compound of the invention is termed a topical formulation or topical composition of the invention.
  • Topical formulations of the invention are prepared by mixing a compound of the invention with a topical carrier according to well-known methods in the art, for example, methods provided by standard reference texts such as, REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY 1577-1591, 1672-1673, 866-885 (Alfonso R. Gennaro ed. 19th ed. 1995); Ghosh, T. K.; et al. TRANSDERMAL AND TOPICAL DRUG DELIVERY SYSTEMS (1997), both of which are hereby incorporated herein by reference.
  • topical carriers useful for topical delivery of compounds of the invention can be any carrier known in the art for topically administering pharmaceuticals, for example, but not limited to, pharmaceutically acceptable solvents, such as a polyalcohol or water; emulsions (either oil-in-water or water-in-oil emulsions), such as creams or lotions; micro emulsions; gels; ointments; liposomes; powders; and aqueous solutions or suspensions.
  • pharmaceutically acceptable solvents such as a polyalcohol or water
  • emulsions either oil-in-water or water-in-oil emulsions
  • creams or lotions such as creams or lotions
  • micro emulsions such as creams or lotions
  • micro emulsions such as creams or lotions
  • gels such as ointments
  • liposomes such as creams or lotions
  • powders such as ointments
  • aqueous solutions or suspensions such
  • the topical carrier used to deliver a compound of the invention is an emulsion, gel, or ointment.
  • Emulsions, such as creams and lotions are suitable topical formulations for use in the invention.
  • An emulsion is a dispersed system comprising at least two immiscible phases, one phase dispersed in the other as droplets ranging in diameter from 0.1 mu m to 100 mu m.
  • An emulsifying agent is typically included to improve stability.
  • the emulsion When water is the dispersed phase and an oil is the dispersion medium, the emulsion is termed a water-in-oil emulsion.
  • the emulsion When an oil is dispersed as droplets throughout the aqueous phase as droplets, the emulsion is termed an oil-in-water emulsion.
  • Emulsions such as creams and lotions that can be used as topical carriers and their preparation are disclosed in REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY 282-291 (Alfonso R. Gennaro ed. 19th ed. 1995, hereby incorporated herein by reference.
  • the topical carrier used to deliver a compound of the invention is a gel, for example, a two-phase gel or a single-phase gel.
  • Gels are semisolid systems consisting of suspensions of small inorganic particles or large organic molecules interpenetrated by a liquid. When the gel mass comprises a network of small discrete inorganic particles, it is classified as a two-phase gel.
  • Single-phase gels consist of organic macromolecules distributed uniformly throughout a liquid such that no apparent boundaries exist between the dispersed macromolecules and the liquid.
  • Suitable gels for use in the invention are disclosed in REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY 1517-1518 (Alfonso R. Gennaro ed. 19th ed. 1995), hereby incorporated herein by reference.
  • Other suitable gels for use with the invention are disclosed in U.S. Pat. No. 6,387,383 (issued May 14, 2002); U.S. Pat. No. 6,517,847 (issued Feb. 11, 2003); and U.S. Pat. No. 6,468,989 (issued Oct. 22, 2002), each of which patents is hereby incorporated herein by reference.
  • the topical carrier used to deliver a compound of the invention is an ointment.
  • Ointments are oleaginous semisolids that contain little if any water.
  • the ointment is hydrocarbon based, such as a wax, petrolatum, or gelled mineral oil.
  • hydrocarbon based such as a wax, petrolatum, or gelled mineral oil.
  • Suitable ointments for use in the invention are well known in the art and are disclosed in REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY 1585-1591 (Alfonso R. Gennaro ed. 19th ed. 1995), hereby incorporated herein by reference.
  • the topical carrier used in the topical formulations of the invention is an aqueous solution or suspension, preferably, an aqueous solution.
  • Suitable topical carriers for use in the invention are disclosed in REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY 1563-1576 (Alfonso R. Gennaro ed. 19th ed. 1995), hereby incorporated herein by reference.
  • Other suitable aqueous topical carrier systems are disclosed in U.S. Pat. No. 5,424,078 (issued Jun. 13, 1995); U.S. Pat. No. 5,736,165 (issued Apr. 7, 1998); U.S. Pat. No. 6,194,415 (issued Feb. 27, 2001); U.S. Pat. No. 6,248,741 (issued Jun. 19, 2001); U.S. Pat. No. 6,465,464 (issued Oct. 15, 2002), all of which patents are hereby incorporated herein by reference.
  • the topical formulations of the invention can comprise pharmaceutically acceptable excipients such as those listed in REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY 866-885 (Alfonso R. Gennaro ed. 19th ed. 1995; Ghosh, T. K.; et al. TRANSDERMAL AND TOPICAL DRUG DELIVERY SYSTEMS (1997), hereby incorporated herein by reference, including, but not limited to, protectives, adsorbents, demulcents, emollients, preservatives, antioxidants, moisturizers, buffering agents, solubilizing agents, skin-penetration agents, and surfactants.
  • pharmaceutically acceptable excipients such as those listed in REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY 866-885 (Alfonso R. Gennaro ed. 19th ed. 1995; Ghosh, T. K.; et al. TRANSDERMAL
  • topical formulations of the invention can include pharmaceuticals or their pharmaceutically acceptable salts, for example, but not limited to, topical corticosteroids and other anti-inflammatory agents, such as betamethasone, diflorasone, amcinonide, fluocinolone, mometasone, hydrocortisone, prednisone, and triamcinolone; local anesthetics and analgesics, such as camphor, menthol, lidocaine, and dibucaine, and pramoxine; antifungals, such as ciclopirox, chloroxylenol, triacetin, sulconazole, nystatin, undecylenic acid, tolnaftate, miconizole, clotrimazole, oxiconazole, griseofulvin, econazole, ketoconozole, and amphotericin B; antibiotics and anti-infectives, such as mupirocin, erythromycin, clindamycin,
  • Dosages and dosing frequency will be determined by a trained medical professional depending on the activity of the compound of the invention, the characteristics of the particular topical formulation, and the identity and severity of the dermatologic disorder treated or prevented.
  • a compound of the invention is present in a formulation of the invention in an amount of from about 0.001% to about 10% of the total weight of the formulation, preferably, of from about 0.05% to about 5%, more preferably, of from about 0.1% to about 2% of the total weight of the formulation.
  • Another aspect of the invention is an article of manufacture that comprises a topical formulation of the invention in a suitable container with labelling and instructions for use.
  • the container can be a dropper or tube with a suitable small orifice size, for instance the topical formulations of the invention can be filled and packaged into a plastic squeeze bottle or tube; or a small-size bottle, a phial or a vial.
  • instructions are packaged with the formulations of the invention, for example, a pamphlet or package label.
  • the labeling instructions explain how to administer topical formulations of the invention, in an amount and for a period of time sufficient to treat the patient.
  • the label includes the dosage and administration instructions, the formulation's composition, the clinical pharmacology, drug resistance, pharmacokinetics, absorption, bioavailability, and contraindications.
  • Fillers can be any product known by the skilled artisan and the preferred compounds are molecules such as Hyaluronic acid, collagen, dextran sulphate, elastine, polyurethane gels, poly-L-lactic acid or calcium hydroxyapatite or silicone or mixture thereof. The most preferred are compounds resorbable such as hyaluronic acid cross-linked or linear.
  • Hyaluronic acid or hyaluronate is a non-sulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is one of the chief components of the extracellular matrix, contributes significantly to cell proliferation and migration. It plays an important role in skin hydration and skin elasticity. The level of hyaluronic acid decreases with ageing in quantity and quality, inducing skin drying which becomes wrinkled.
  • Hyaluronic acid is highly soluble in water and forms solutions with high viscosity levels. Therefore, it is widely used as pharmaceutical product.
  • the safety of this compound is considered to be very safe since no immunogenicity reaction has been observed. Few minor adverse events have been noticed.
  • the filler is hyaluronic acid or a pharmaceutically acceptable salt or derivative thereof, particularly the sodium or potassium salt.
  • Hyaluronic acid can be used under different forms: salts thereof, derivatives thereof such as esters or amides, in a linear form or cross-linked.
  • the molecular weight typically comprised between 500 kDa and 5 000 kDa, and the degree of cross-linking depends on the application, especially on the depth of the wrinkles to be filled.
  • pharmaceutically acceptable salt(s) means those salts of compounds of the invention that are safe and effective for topical use in mammals and that possess the desired biological activity.
  • Pharmaceutically acceptable salts include salts of acidic or basic groups present in compounds of the invention.
  • Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleat, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzensulfonate, p-toluenesulfonate and pamoate (i.e., 1,1′-methylene-bis-(2-hydroxy-3-naphthoate)) salts. Certain compounds of the invention can form pharmaceutically acceptable salts with various amino acids.
  • Suitable base salts include, but are not limited to, aluminum, calcium, lithium, magnesium, potassium, sodium, zinc, and diethanolamine salts.
  • a topical formulation in the context of the invention any formulation which is pharmaceutically acceptable for topical delivery of the compounds of the invention.
  • a topical formulation will comprise at least a compound of the invention.
  • the choice of topical formulation will depend on several factors, including the nature of the symptoms to be treated or prevented, the physiochemical characteristics of the particular compound of the invention and of other excipients present, their stability in the formulation, available manufacturing equipment, and cost constraints.
  • a “therapeutically effective amount of a compound of the invention” means the minimum amount of the compound that is effective to obtain the desired effect in the context of the invention.
  • the term “subject” or “patient” are used equivalently and means any animal, preferably a mammal, more preferably, a human to which will be or has been administered compounds or formulations of the invention.
  • Figures are photographs of skin treatment with brimonidine (including both treated (Z4) and non-treated area in the same picture (Z3) taken immediately and 2-5 and 10 minutes after the dermabrasion.
  • a aqueous solution topical formulation of the invention comprises (5-Bromo-quinoxalin-6-yl)-(4,5-dihydro-IH-imidazol-2-yl)-amine-L-tartrate, (brimonidinetartrate) (0.15 wt. %); benzalkonium chloride (0.005 wt. %) as a preservative; and the inactive ingredients: boric acid; calcium chloride; magnesium chloride; potassium chloride; purified water; sodium borate; sodium carboxymethylcellulose; sodium chloride; with hydrochloric acid and/or sodium hydroxide to adjust the pH to 5.6 to 6.6.
  • the osmolality is in the range of 250-350 mOsmol/Kg.
  • the ingredients are mixed together and aqueous sodium hydroxide is slowly added to the mixture until a pH of about 7 is reached and the gel is formed.
  • the objectives of this study were to assess the local dermal effect of single dermal application of Brimonidine Gel placebo or 1% applied on delimited abraded mini-zone (2.8 cm 2 and different dermabraded skin conditions) in the Gottingen® minipig.
  • ⁇ 2A-adrenoceptor (Brimonidine) which is a well-known potent vasoconstrictor* in the porcine species is evaluated with regards to different skin dermabrasion conditions in order to evaluate the cutaneous reactions and particularly the redness/bleeding kinetics modifications.
  • each zone is clipped free from hair.
  • 4 minizones (2 on either side) is delimited using Ringflost® and surrounded with an indelible pen.
  • the animal is anesthetized (Zoletil®) before dermabrasion.
  • Each minizone is disinfected with chlorexidine.
  • the experimental conditions used for each zone is set as follows:
  • the Brimonidine gel 1% is gently applied 5 minutes prior to the dermabrasion procedure.
  • the cutaneous reaction is evaluated immediately, and 2-5 and 10 minutes after the dermabrasion procedure.
  • the skin is examined to evaluate the degree of erythema, edema, desquamation, scab formation and any other lesions. Cutaneous reaction is evaluated according to the grading scale describe in “OCDE Guideline No. 404. Acute dermal irritation/corrosion”. If feasible, cutaneous reactions evaluation will be performed by the same persons during the whole study.
  • the duration of treatment was one day. Thereafter each zone is covered with Tegaderm® dressings until complete wound healing process.
  • Photographs (including both treated and non-treated area in the same picture) will be taken immediately and 2-5 and 10 minutes after the dermabrasion procedure.
  • Painkiller (1 mL per animal, Finadyne®) is used after the 20 minutes dermal evaluation completion.
  • the Laser used is Erbium Yag, 2940 nm BURANE XL from Wavelight aesthetics (Quantel)
  • this example shows that Brimonidine is capable of decreasing cutaneous reactions during aesthetic or surgery procedures and particularly of alleviating bruising or bleeding reactions.
US13/322,245 2009-05-29 2010-05-28 Combination of adrenergic receptor agonist alpha-1 or alpha-2, preferably brimonidine with fillers, preferably hyaluronic acid Abandoned US20120295914A1 (en)

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PCT/EP2010/057469 WO2010136585A2 (en) 2009-05-29 2010-05-28 Combination of adrenergic receptor agonist -1 or -2, preferably brimonidine with fillers, preferablyhyaluronic acid

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11155802B2 (en) 2017-07-06 2021-10-26 Merz Pharma Gmbh & Co. Kgaa Recombinant botulinum neurotoxins with increased duration of effect
US11952601B2 (en) 2017-06-20 2024-04-09 Merz Pharma Gmbh & Co. Kgaa Recombinant botulinum toxin with increased duration of effect
US11969461B2 (en) 2016-03-02 2024-04-30 Merz Pharma Gmbh & Co. Kgaa Composition comprising botulinum toxin

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7758872B1 (en) * 2003-02-07 2010-07-20 Eric Finzi Method of treating depression
US8410102B2 (en) 2003-05-27 2013-04-02 Galderma Laboratories Inc. Methods and compositions for treating or preventing erythema
US8357795B2 (en) 2008-08-04 2013-01-22 Allergan, Inc. Hyaluronic acid-based gels including lidocaine
AU2010232547A1 (en) * 2009-04-02 2011-10-27 Allergan, Inc. Hair-like shaped hydrogels for soft tissue augmentation
US9101538B2 (en) * 2009-05-20 2015-08-11 Donna M. Tozzi Injectable amino-acid composition
US20110172180A1 (en) 2010-01-13 2011-07-14 Allergan Industrie. Sas Heat stable hyaluronic acid compositions for dermatological use
US20110171310A1 (en) * 2010-01-13 2011-07-14 Allergan Industrie, Sas Hydrogel compositions comprising vasoconstricting and anti-hemorrhagic agents for dermatological use
US9114188B2 (en) 2010-01-13 2015-08-25 Allergan, Industrie, S.A.S. Stable hydrogel compositions including additives
US20110171311A1 (en) * 2010-01-13 2011-07-14 Allergan Industrie, Sas Stable hydrogel compositions including additives
CA2792646C (en) * 2010-03-26 2018-11-20 Galderma Research & Development Improved uses and compositions for safe and effective treatment of erythema
KR20130010122A (ko) 2010-03-26 2013-01-25 갈데르마 리써어치 앤드 디벨로프먼트 모세혈관 확장증의 안전하고 유효한 치료를 위한 개선된 방법 및 조성물
US9179531B2 (en) 2010-05-02 2015-11-03 Melito Inc Super conducting super capacitor
US8053427B1 (en) 2010-10-21 2011-11-08 Galderma R&D SNC Brimonidine gel composition
US20130261126A1 (en) 2010-10-21 2013-10-03 Galderma S.A. Brimonidiine gel compositions and methods of use
AU2012276512B2 (en) * 2011-06-27 2016-04-21 Sang Duck Kim Pharmaceutical composition for treating scars on the skin, and method for treating scars on the skin using same
FR2977493B1 (fr) * 2011-07-05 2014-02-14 Galderma Res & Dev Nouvelle composition anesthesique stable pour la reduction des reactions cutanees
US9283217B2 (en) 2011-11-10 2016-03-15 Allergan, Inc. Pharmaceutical compositions comprising 7-(1 H-imidazol-4-ylmethyl)-5,6,7,8-tetrahydro-quinoline for treating skin diseases and conditions
US20140105959A1 (en) * 2012-10-12 2014-04-17 Allergan, Inc. Method and device for reducing dermal filler adverse events
KR20140147950A (ko) * 2013-06-20 2014-12-31 서울대학교산학협력단 필러와 보틀리눔 독소를 포함하는 피부 주름, 노화 개선 또는 신경근육 관련 질환 치료용 조성물
US9421198B2 (en) 2013-07-30 2016-08-23 Teoxane Composition comprising hyaluronic acid and mepivacaine
US9480731B2 (en) 2013-12-12 2016-11-01 Medy-Tox, Inc. Long lasting effect of new botulinum toxin formulations
RU2566061C1 (ru) * 2014-12-17 2015-10-20 Ольга Марселевна Капулер Способ комплексной коррекции мимических морщин периорбитальной области
WO2016198641A1 (en) 2015-06-12 2016-12-15 Laboratoire Francais Du Fractionnement Et Des Biotechnologies Injectable composition of factor vii and fillers
RU2611929C1 (ru) * 2015-12-01 2017-03-01 Ольга Марселевна Капулер Способ коррекции инволюционных изменений подбородочной области
FR3058064B1 (fr) * 2016-10-28 2020-08-07 Lab Vivacy Composition a base d'acide hyaluronique comprenant de la mepivacaine
KR102039608B1 (ko) * 2017-11-03 2019-11-01 주식회사 셀버틱스 미도드린을 포함하는 조성물 및 이의 용도

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040242588A1 (en) * 2003-05-27 2004-12-02 Jack Dejovin Compounds, formulations, and methods for treating or preventing rosacea
US20060003033A1 (en) * 2004-06-29 2006-01-05 Mcclellan Stephanie N Topical compositions for anti-aging and methods of using same
WO2009065116A1 (en) * 2007-11-16 2009-05-22 Aspect Pharmaceuticals Llc Compositions and methods for treating purpura

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8029A (en) * 1851-04-08 Kellogg
JPH01265970A (ja) * 1988-04-19 1989-10-24 Shiseido Co Ltd ヒアルロン酸を含有させたコラーゲン水溶液又は水分散液
JPH05306231A (ja) * 1992-04-24 1993-11-19 Pola Chem Ind Inc 皮膚外用剤
JPH05345713A (ja) * 1992-06-15 1993-12-27 Kao Corp 皮膚外用剤
JP3091040B2 (ja) * 1993-02-12 2000-09-25 丸善製薬株式会社 皮膚化粧料
JP2995090B2 (ja) * 1993-03-19 1999-12-27 キユー・メド・アクチエボラーグ 組織増大のための組成物および方法
JPH06312920A (ja) * 1993-05-06 1994-11-08 Kao Corp 美白剤及びこれを含有する皮膚化粧料
US5643586A (en) * 1995-04-27 1997-07-01 Perricone; Nicholas V. Topical compositions and methods for treatment of skin damage and aging using catecholamines and related compounds
RU2159111C1 (ru) * 1999-08-02 2000-11-20 Общество с ограниченной ответственностью "Новые медицинские технологии" Композиция для ухода за кожей лица
AU2001259848B2 (en) * 2000-05-12 2005-10-13 Septodont Holding Sas Local anesthetic methods and kits
JP4820024B2 (ja) * 2001-01-10 2011-11-24 昭和薬品化工株式会社 局所麻酔用組成物
US20050196370A1 (en) * 2003-03-18 2005-09-08 Zhi-Jian Yu Stable ophthalmic oil-in-water emulsions with sodium hyaluronate for alleviating dry eye
WO2006020994A2 (en) * 2004-08-13 2006-02-23 Angiotech International Ag Compositions and methods using hyaluronic acid and hyluronidase inhibitors
EP1858502A1 (en) * 2005-03-04 2007-11-28 Acure Pharma AB Methods and pharmaceutical compositions for the treatment of neurological damage
US20060211665A1 (en) * 2005-03-17 2006-09-21 Ranawat Chitranjan S Reduction of postoperative pain medication
US20070082070A1 (en) * 2005-10-11 2007-04-12 Stookey Evangeline L Treating skin disorders
TW200735906A (en) * 2005-11-03 2007-10-01 Rseal Internat Ltd Partnership Continuously sealing one way valve assembly and fluid delivery system and formulations for use therein
TW200733993A (en) * 2005-11-03 2007-09-16 Reseal Internat Ltd Partnership Continuously sealing one way valve assembly and fluid delivery system and formulations for use therein
CN1883439A (zh) * 2006-05-30 2006-12-27 蒙一纯 美容填充生物材料与微针阵列结合技术及应用方法
US20080293728A1 (en) * 2007-05-18 2008-11-27 Mcintire Gregory L Complexes Comprising alpha2-Adrenergic Receptor Agonists and Compositions
EP2162158A2 (en) * 2007-05-23 2010-03-17 Allergan, Inc. Coated hyaluronic acid particles
PT2182960E (pt) * 2007-07-27 2014-06-11 Galderma Lab Inc Compostos, formulações e métodos para a redução das rugas, da flacidez e dos sulcos na pele
US20090061020A1 (en) * 2007-08-31 2009-03-05 Theobald Klaus P Brimonidine Compositions for Treating Erythema
MX2007011165A (es) * 2007-09-12 2009-03-11 Arturo Jimenez Bayardo Composición farmacéutica estable de timolol, dorzolamida y brimonidina.
US7910134B2 (en) * 2007-10-29 2011-03-22 Ayman Boutros Alloplastic injectable dermal filler and methods of use thereof
CA2709199A1 (en) * 2007-12-21 2009-07-02 Galderma Laboratories, Inc. Pre-surgical treatment
CA2713878C (en) * 2008-02-15 2017-01-31 Bone Therapeutics Pharmaceutical composition for use in the treatment or prevention of osteoarticular diseases
US8283350B2 (en) * 2008-08-01 2012-10-09 Alpha Synergy Development, Inc. Compositions and methods for reducing capillary permeability
US20110172180A1 (en) * 2010-01-13 2011-07-14 Allergan Industrie. Sas Heat stable hyaluronic acid compositions for dermatological use
US20110171310A1 (en) * 2010-01-13 2011-07-14 Allergan Industrie, Sas Hydrogel compositions comprising vasoconstricting and anti-hemorrhagic agents for dermatological use

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040242588A1 (en) * 2003-05-27 2004-12-02 Jack Dejovin Compounds, formulations, and methods for treating or preventing rosacea
US20060003033A1 (en) * 2004-06-29 2006-01-05 Mcclellan Stephanie N Topical compositions for anti-aging and methods of using same
WO2009065116A1 (en) * 2007-11-16 2009-05-22 Aspect Pharmaceuticals Llc Compositions and methods for treating purpura

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11969461B2 (en) 2016-03-02 2024-04-30 Merz Pharma Gmbh & Co. Kgaa Composition comprising botulinum toxin
US11952601B2 (en) 2017-06-20 2024-04-09 Merz Pharma Gmbh & Co. Kgaa Recombinant botulinum toxin with increased duration of effect
US11155802B2 (en) 2017-07-06 2021-10-26 Merz Pharma Gmbh & Co. Kgaa Recombinant botulinum neurotoxins with increased duration of effect

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