WO2014176417A1 - Préparation topique pour contourner un tractus gastro-intestinal, administration d'agents thérapeutiques et système d'administration de médicament trans-épithéliale - Google Patents

Préparation topique pour contourner un tractus gastro-intestinal, administration d'agents thérapeutiques et système d'administration de médicament trans-épithéliale Download PDF

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Publication number
WO2014176417A1
WO2014176417A1 PCT/US2014/035285 US2014035285W WO2014176417A1 WO 2014176417 A1 WO2014176417 A1 WO 2014176417A1 US 2014035285 W US2014035285 W US 2014035285W WO 2014176417 A1 WO2014176417 A1 WO 2014176417A1
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Prior art keywords
therapeutic
topical composition
delivering
driver
further defined
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PCT/US2014/035285
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English (en)
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Michael Greenspan
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Sambria Pharmaceuticals, Llc
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Publication of WO2014176417A1 publication Critical patent/WO2014176417A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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

Definitions

  • the present invention relates to methods and topical compositions for drug delivery. More specifically, the present invention relates to topical compositions that bypass Gl tract absorption, deliver therapeutics, and avoid first pass effect.
  • Local anesthetics are used in many medical procedures in order to prevent or relieve pain, itching, and burning for a temporary period of time through the blocking of nerve signals and are advantageous when rapid relief is needed.
  • procedures that local anesthetics are used in include dental procedures such as teeth cleaning and filling cavities, and minor surgeries.
  • Local anesthetics are of two different types, aminoamides and aminoesters.
  • the aminoamides include articaine, bupivacaine, cinchocaine, etidocaine, levobupivacaine, lidocaine, mepivacaine, prilocaine, ropivacaine, and trimecaine.
  • the aminoesters include benzocaine, chloroprocaine, cyclomethycaine, dimethocaine, piperocaine, propoxycaine, procaine, proparacaine, and tetracaine.
  • Local anesthetics can be used topically or injected.
  • U.S. Patent Nos. 5,650,157, 5,709,855, and 6,201 ,022 to Bockow disclose topical analgesic creams that have superior transdermal absorption and absorption speed.
  • Some otherwise desirable oil compositions derived from natural sources are characterized by an unpleasant odor. Fractions or combinations of such oils may also be so characterized.
  • Stable, deodorized oils may be prepared by adding an amount of a deodorizing agent effective to substantially reduce the odor of the derived oil composition, fraction or combination thereof to that oil composition, fraction or combination.
  • the pharmaceutical topical compositions of these patents contain these stable, deodorized oil compositions and exhibit enhanced penetration properties and achieve enhanced patient response.
  • a composition for preventing or treating inflammation and/or pain by topical administration are disclosed.
  • the composition contains an omega fatty acid in combination with spirulina.
  • the omega fatty acid is a mixture of omega-3 fatty acids and omega-6 fatty acids.
  • Omega-3 fatty acids include eicosapentaenoic acid and docosahexanoic acid
  • omega-6 fatty acids include gamma-linolenic acid and dihomo-gamma-linolenic acid.
  • the composition may further include pharmaceutically acceptable carriers or diluents, vitamins A and E, and a cyclooxygenase inhibitor such as methyl salicylate.
  • the pharmaceutical compositions can be used to manage pain and/or to treat the underlying ailments. Methods of making such topical pharmaceutical compositions are also discussed.
  • drugs that undergo a first pass effect with oral administration include alprenolol, amitriptyline, dihydroergotamine, 5- fluorouracil, hydralazine, isoprenaline (isoproterenol), lignocaine (lidocaine), lorcainide, pethidine (meperidine), mercaptopurine, metoprolol, morphine, neostigmine, nifedipine, pentazocine and propranolol.
  • larger oral doses must be given to a patient. This can result in negative side effects. Otherwise, intravenous administration must be used to avoid this.
  • U.S. Patent No. 5,837,289 to Grasela discloses a transdermal administration composition that includes at least two penetration enhancers of ethoxydiglycol and isopropyl miristate.
  • a method for disrupting epithelial barrier function in a host in need of the topical administration of a physiologically active substance which comprises applying to the epithelium of the host, barrier-disrupting amount of at least one agent selected from the group consisting of an inhibitor of ceramide synthesis, inhibitor of acylceramide synthesis, inhibitor of glucosylceramide synthesis, and inhibitor of sphingomyelin synthesis, an inhibitor of fatty acid synthesis, an inhibitor of cholesterol synthesis, a degradation enzyme of ceramides, acylceramide, glucosylceramides, sphingomyelin, an inhibitor of phospholipid, glycosphingolipid, including glucosylceramide, acylceramide or sphingomyelin degradation, and both inhibitors and stimulators of metabolic enzymes of free fatty acids, ceramide, and cholesterol, as well as a topical composition useful therefor.
  • U.S. Patent No. 6,582,724 to Hsu, et al. discloses a permeation enhancer composition for increasing the permeability of skin or mucosal tissue to topically or transdermal ⁇ administered pharmacologically or cosmeceutically active agents.
  • the composition is comprised of a hydroxide-releasing agent and a lipophilic co-enhancer such as a fatty alcohol, a fatty ether, or a fatty acid ester, including fatty acid esters of polyols such as propylene glycol and glycerol.
  • Methods of administering active agents topically with enhanced permeation are also disclosed.
  • U.S. Patent No. 6,689,399 to Dickson discloses an anti-inflammatory composition for treatment of joint and muscle pain through transdermnal delivery of a capsacinoid in conjunction with glucosamine.
  • U.S. Patent Application Publication No. 2007/0243132 to Russell-Jones, et al. discloses a topical delivery system of microemulsions which assists penetration of a desired pharmaceutically active agent, such as peptides, polypeptides and proteins, water soluble vitamins, NSAIDs, genetic molecules and chemical compounds into the skin, which does not necessitate the use of chemical enhancers, nor electrical or ultrasonic energy to facilitate penetration into and though the skin.
  • a desired pharmaceutically active agent such as peptides, polypeptides and proteins, water soluble vitamins, NSAIDs, genetic molecules and chemical compounds into the skin, which does not necessitate the use of chemical enhancers, nor electrical or ultrasonic energy to facilitate penetration into and though the skin.
  • compositions and transdermal drug delivery systems of synthetic local anesthetic and/or synthetic glucocorticoids and/or non-steroidal anti-inflammatory agents for the treatment and/or relief of symptoms associated with carpal tunnel syndrome or tendonitis.
  • a high throughput screening and isolation system that identifies rare enhancer mixtures from a candidate pool of penetration enhancer combinations, an active component, such as a drug, is then combined with the combination in a formulation which is tested for the ability of the drug to penetrate into or through skin, and specific unique and rare mixtures of chemical penetration enhancers that enhance skin permeability to hydrophilic macromolecules by more than 50-fold without inducing skin irritation, such as combinations of sodium laurel ether sulfate and 1 -phenyl piperazine, and combinations of N-lauryl sarcosine and Span 20/sorbitan monolaurate.
  • the present invention provides for a topical composition for therapeutic delivery including a driver for delivering a therapeutic to the bloodstream and having the ability to bypass the Gl tract, avoid side effects of oral administration, and avoid a first pass effect, and an effective amount of said therapeutic.
  • the present invention also provides for a method of delivering a therapeutic by applying a topical composition including a driver and a therapeutic to a subject's skin, and delivering the therapeutic to the bloodstream and bypassing the Gl tract.
  • the present invention provides for a method of delivering a therapeutic by applying a topical composition including a driver and a therapeutic to a subject's skin, and delivering the therapeutic to the bloodstream and avoiding side effects of oral administration.
  • the present invention further provides for a method of delivering a therapeutic by applying a topical composition including a driver and a therapeutic to a subject's skin, and delivering the therapeutic to the bloodstream and avoiding a first pass effect.
  • the present invention provides generally for a topical composition for delivery of therapeutics that bypasses the Gl tract and avoids first pass metabolism (i.e. avoids the therapeutic being absorbed by the digestive system and entering the hepatic portal system where it is metabolized by the liver, reducing bioavailability), and that reduces or eliminates side effects of oral administration.
  • the topical composition can avoid many problems experienced with oral administration of drugs due to the nature of the drugs or conditions of the patient when the drugs are desired to be taken.
  • the topical composition can include any drivers that are capable of delivering the therapeutics to the bloodstream through topical administration.
  • the drivers can deliver the therapeutics to the bloodstream while bypassing the Gl tract.
  • the drivers allow for avoiding first pass metabolism.
  • the drivers are able to provide deep penetration of the therapeutics into the skin and subsequently into the bloodstream.
  • the drivers are able to provide a better uptake of therapeutics into the skin and the bloodstream than currently available drivers. Because of this, not only are therapeutics able to be delivered that previously have not been able to be delivered topically, but lower doses of the therapeutics can be used to provide a therapeutic effect than have been previously used, further reducing negative side effects.
  • the drivers are also able to deliver therapeutics in a range of molecular sizes, even over 500 kDa.
  • the topical composition preferably includes a driver including an amino benzoate local anesthetic, methylsulfonylmethane (MSM), and ethoxydiglycol.
  • a driver including an amino benzoate local anesthetic, methylsulfonylmethane (MSM), and ethoxydiglycol.
  • MSM methylsulfonylmethane
  • ethoxydiglycol ethoxydiglycol
  • amino benzoate local anesthetics can be used, such as, but not limited to, lidocaine, benzocaine (5-10%), prilocaine (1 %), and tetracaine (2%).
  • any other suitable local anesthetic can be used (not necessarily an amino benzoate), such as, but not limited to, amylocaine, articaine, benzonatate, bupivacaine, butacaine, chloroprocaine, cinchocaine, dimethocaine, eucaine, etidocaine, hexylcaine, levobupivacaine, mepivacaine, meprylcaine, metabutoxycaine, orthocaine, oxetacaine, oxybuprocaine, phenacaine, piperocaine, pramocaine, procaine, proparacaine, propoxycaine, quinisocaine, ropivacaine, or trimecaine
  • the amino benzoate local anesthetic is preferably lidocaine (or lidocaine HCI), also known as 2-(diethylamino)-/V-(2,6-dimethylphenyl)acetamide shown in Formula (I).
  • lidocaine or lidocaine HCI
  • Lidocaine can be administered in amounts of 0.5 to 4.5 mg/kg/dose.
  • the lidocaine can be in the form of viscous lidocaine 2% generally used to treat sore throat, teething, mouth or esophageal sores, or swelling inside the mouth. Viscous lidocaine can also be used to prevent gagging during dental procedures.
  • Lidocaine spray 4% can be used under "crash" circumstances, where speed is of the essence. Lidocaine spray is generally used when a breathing tube is inserted down the larynx during intubation to numb the gag reflex.
  • Lidocaine spray can also be used during childbirth. Lidocaine spray is also available in 10%, and the maximum dose per day is 30 mg within 30 minutes.
  • Other amino benzoate local anesthetics with similar dosing to lidocaine include tetracaine (2-(dimethylamino)ethyl 4-(butylamino)benzoate), shown in Formula (II), and benzocaine (ethyl 4-aminobenzoate), shown in Formula (III).
  • MSM (formula (CH 3 ) 2 SO 2 ) is an organosulfur compound, and also known as DMSO 2 , methyl sulfone, and dimethyl sulfone. MSM is currently available as a dietary supplement for osteoarthritis. MSM can be administered in up to 6 g/day.
  • Ethoxydiglycol also known as diethylene glycol monethyl ether, formula CH 3 CH 2 OCH 2 CH 2 OCH 2 CH 2 OH
  • the CAS registry number is 1 1 1 -90-0.
  • the composition can further include various carriers and excipients such as, but not limited to, water, polyacrylamide (a flocculant), C13-14 isoparaffin (an emollient), laureth-7 (surfactant and emulsifier), propylene glycol (penetration enhancer), triethanolamine (pH balancer), emu oil (antifungal agent), tea tree oil (antifungal agent), arnica Montana extract (anti-inflammatory), ethylhexylglycerin (deodorizing agent), phenoxyethanol (bactericide), isopropyl palmitate (emollient, moisturizer, thickening agent, anti-static), stearic acid (surfactant and softening agent), glucosamine sulfate (anti-arthritic), and chondroitin sulfate (anti-arthritic).
  • An example formulation is provided in Table 1 , along with possible ranges for the components. Any other suitable excipients in these categories can also be used.
  • Emu Oil 0.25% 0.10-5%
  • Arnica Montana Extract 0.50% 0.10-5%
  • the composition can also include agents that assist in maintaining the molecular structure integrity of the therapeutic or help deliver the therapeutic through the skin, such as, but not limited to, solvents that break down lipophilic therapeutics or adjust ionic charge for easier delivery into skin, detergents (such as, but not limited to, anionic detergents (alkylbenzenesulfonates), cationic detergents, non-ionic detergents (ethoxylates, PEGylates), or zwitterionic detergents (3-[(3- cholamidopropyl)dimethylammonio]-1 -propanesulfonate)), cyclodextrins (that readily complex with lipophilic therapeutics like steroids, including cc-cyclodextrin, ⁇ - cyclodextrin, and ⁇ -cyclodextrin), other complexing agents (i.e.
  • detergents such as, but not limited to, anionic detergents (alkylbenzenesulfonates), cationic detergents, non-
  • chelating agents with two or more separate coordinate bonds between a multiple bonded ligand and a central atom (metal), such as, but not limited to, glutamic acid, histidine, malate, phytochelatin, hemoglobin, chlorophyll, ethylenediaminetetraacetic acid (EDTA), amino acid chelates, and dimercaprol), and other amphipathic chemicals.
  • metal such as, but not limited to, glutamic acid, histidine, malate, phytochelatin, hemoglobin, chlorophyll, ethylenediaminetetraacetic acid (EDTA), amino acid chelates, and dimercaprol
  • the topical composition can further include at least one therapeutic.
  • a symphony of therapeutics is delivered that harmonize within the body. This harmonization can occur because they address different symptoms of an ailment or disease at the same time and through administration in the same topical composition. The harmonization can also occur because different ingredients and/or therapeutics within the topical composition metabolize each other to an active compound.
  • the therapeutic can be one that has the side effect of Gl tract irritation when administered orally, such as, but not limited to, benzonatate, brimonidine, carboplatin, chloride ion, colestipol, colistin, dextrose, dicloxacillin, doxazosin, estramustine phosphate sodium, glipizide, imatinib mesylate, insulin recombinant human, lenalidomide, meloxicam, metformin, moricizine, myambutol, naltrexone, nifedipine, nystatin, oxacillin, penicillin g, phenoxybenzamine, procainamide hydrochloride, telithromycin, or tramadol.
  • benzonatate brimonidine
  • carboplatin chloride ion
  • colestipol colestipol
  • colistin dextrose
  • dicloxacillin doxazosin
  • the therapeutic can be at least one analgesic for relieving pain.
  • the analgesic can be a non-steroidal anti-inflammatory drug (NSAID) such as, but not limited to, acetaminophen, salicylates (aspirin, diflunisal, salsalate), acetic acid derivatives (indomethacin, ketorolac, sulindac etodolac, diclofenac, nabumetone), propionic acid derivatives (ibuprofen, naproxen, flurbiprofen, ketoprofen, oxaprozin, fenoprofen, loxoprofen), fenamic acid derivatives (meclofenamic acid, mefenamic acid, flufenamic acid, tolfenamic acid), oxicam (enolic acid) derivatives (piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam, isoxicam), aryl
  • the therapeutic can be one that has a first pass effect when administered orally, such as, but not limited to, alprenolol, amitriptyline, buprenorphine, cimetidine, diazepam, demerol, dihydroergotamine, 5-fluorouracil, hydralazine, imipramine, isoprenaline (isoproterenol), lorcainide, pethidine (meperidine), mercaptopurine, metoprolol, midazolam, morphine, neostigmine, nifedipine, pentazocine, propranolol, lidocaine, or verapamil. Combinations of any of the therapeutics described herein can also be used.
  • the therapeutic can also be generally from the classes antihistamines, anti-infective agents, antineoplastic agents, autonomic drugs, blood derivatives, blood formation, coagulation, and thrombosis agents, cardiovascular drugs, cellular therapy, central nervous system agents, contraceptives, dental agents, diagnostic agents, disinfectants, electrolytic, caloric, and water balance, enzymes, respiratory tract agents, eye, ear, nose, and throat preparations, gold compounds, heavy metal antagonists, hormones and synthetic substitutes, oxytocics, radioactive agents, serums, toxoids, and vaccines, skin and mucous membrane agents, smooth muscle relaxants, and vitamins.
  • the topical composition can also be used with therapeutics that are commonly or otherwise formulated as prodrugs.
  • the prodrugs are normally activated during first pass metabolism. Examples include, but are not limited to, antibiotics such as chloramphenicol, and anticancer drugs such as taxols and cisplatin. Examples of prodrugs include, but are not limited to, using boronate derivatives, using ester forms of the therapeutic that are subsequently hydrolyzed, using forms of the therapeutic that must be phosphorylated.
  • the prodrug can be bioactivated inside cells (intracellular ⁇ ) or outside cells (extracellularly).
  • the therapeutic can be administered in the present invention without the prodrug portion because the active therapeutic can be delivered with high efficiency to the blood without modification in any way, or a different type of prodrug can be used that captures its pathway that otherwise would be downstream of the hepatic portal.
  • the topical composition can be in any number of forms.
  • the topical composition is a cream or gel that can be applied to an affected area of the skin of a subject (human or animal).
  • the topical composition can be in the form of a patch that releases the composition into the skin.
  • the topical composition can also be a spray (aerosol or non-aerosol). Different release profiles can be achieved with different forms, such as rapid release, extended release, or sustained release.
  • the topical composition can be applied multiple times a day, once per day, or as often as needed.
  • the treatment of the patient can be multi-site, by administering the present invention at the temples, injections in the back of the neck, or any other desired site or combinations of sites.
  • Topical composition can be by transdermal (across the skin) or subdermal (underneath the skin) methods.
  • subdermal methods it should be understood that application is by injection or implantation in the methods described below.
  • the topical composition can be delivered directly into the blood stream as well, such as by injection.
  • the present invention provides generally for a method of delivering a therapeutic, by applying the topical composition to a subject's skin, and delivering the therapeutic to the bloodstream while bypassing the Gl tract.
  • a synergistically effective amount of the topical composition and the therapeutic can be used, and lower than normal doses can be used for the therapeutic due to the synergy.
  • the present invention has the advantage of being able to deliver a therapeutic to any area of the body desired and bypassing the Gl tract because the topical composition can be applied to a particular area of the body. This is particularly advantageous in delivering therapeutics to subjects with digestive problems, whether caused by disorders or illnesses such as the flu. Furthermore, with more vascular exposure to the therapeutic, a greater delivery of the therapeutic can be achieved proximal to the site of function of the therapeutic.
  • the present invention provides generally for a method of delivering a therapeutic, by applying the topical composition including the therapeutic to a subject's skin, and delivering the therapeutic to the blood stream and avoiding side effects of oral administration.
  • a synergistically effective amount of the topical composition and the therapeutic can be used, and lower than normal doses can be used for the therapeutic due to the synergy.
  • the present invention has the advantage of being able to deliver a therapeutic to any area of the body desired without the unwanted side effects experienced with oral administration because the topical composition can be applied to a particular area of the body. With more vascular exposure to the therapeutic, a greater delivery of the therapeutic can be achieved proximal to the site of function.
  • the topical composition can include an analgesic and a muscle relaxer in order to avoid side effects commonly experienced with taking these two therapeutics separately.
  • a combined anti-spasmodic effect and anti-pain effect are experienced, providing a symphony of functional results: i.e. a relief from pain as well as a relief from spasms.
  • the present invention provides generally for a method of delivering a therapeutic, by applying the topical composition to a subject's skin, and delivering the therapeutic to the blood stream while avoiding first pass metabolism.
  • a synergistically effective amount of the topical composition and the therapeutic can be used, and lower than normal doses can be used for the therapeutic due to the synergy.
  • the present invention has the advantage of being able to deliver a therapeutic to any area of the body desired and avoiding first pass metabolism because the topical composition can be applied to a particular area of the body and does not require oral administration.
  • the therapeutics do not have to pass into blood vessels via the stomach lining or intestinal lining. This avoids effects due to acid in the stomach and avoids subsequent enzymatic metabolism that dramatically lowers effectiveness. Doses can be lower to achieve a greater bioavailability than with oral doses, thereby reducing unwanted side effects because the therapeutics are delivered with high efficiency to the blood. Furthermore, with more vascular exposure to the therapeutic, a greater delivery of the therapeutic can be achieved proximal to the site of function.
  • composition of the present invention can provide different biodistribution than other delivery vehicles. Different formulations and doses can be used depending on a subject's fat content, as some therapeutic can be lost to the fat layer (the rate and extent of the diffusion of the therapeutic and amino benzoate local anesthetic can vary).
  • the compound of the present invention is administered and dosed in accordance with good medical practice, taking into account the clinical condition of the individual patient, the site and method of administration, scheduling of administration, patient age, sex, body weight and other factors known to medical practitioners.
  • the pharmaceutically "effective amount" for purposes herein is thus determined by such considerations as are known in the art. The amount must be effective to achieve improvement including but not limited to improved survival rate or more rapid recovery, or improvement or elimination of symptoms and other indicators as are selected as appropriate measures by those skilled in the art.
  • the compound of the present invention can be administered in various ways. It should be noted that it can be administered as the compound and can be administered alone or as an active ingredient in combination with pharmaceutically acceptable carriers, diluents, adjuvants and vehicles.
  • the patient being treated is a warm-blooded animal and, in particular, mammals including man.
  • the pharmaceutically acceptable carriers, diluents, adjuvants and vehicles as well as implant carriers generally refer to inert, non-toxic solid or liquid fillers, diluents or encapsulating material not reacting with the active ingredients of the invention.
  • the doses can be single doses or multiple doses over a period of several days.
  • the treatment generally has a length proportional to the length of the disease process and drug effectiveness and the patient species being treated.

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  • Veterinary Medicine (AREA)
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  • Dermatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition topique pour une administration thérapeutique, comprenant un pilote pour administrer un agent thérapeutique à la circulation sanguine et ayant la capacité de contourner le tractus gastro-intestinal, d'éviter des effets secondaires d'une administration orale et d'éviter un effet de premier passage, et une quantité efficace de l'agent thérapeutique. L'invention concerne un procédé pour administrer un agent thérapeutique en appliquant une composition topique, comprenant un pilote et un agent thérapeutique, à la peau d'un sujet, et en administrant l'agent thérapeutique à la circulation sanguine et en contournant le tractus gastro-intestinal. L'invention concerne un procédé pour administrer un agent thérapeutique en appliquant une composition topique, comprenant un pilote et un agent thérapeutique, à la peau d'un sujet, et en administrant l'agent thérapeutique à la circulation sanguine et en évitant des effets secondaires d'une administration orale. L'invention concerne un procédé pour administrer un agent thérapeutique en appliquant une composition topique, comprenant un pilote et un agent thérapeutique, à la peau d'un sujet, et en administrant l'agent thérapeutique à la circulation sanguine et en évitant un effet de premier passage.
PCT/US2014/035285 2013-04-24 2014-04-24 Préparation topique pour contourner un tractus gastro-intestinal, administration d'agents thérapeutiques et système d'administration de médicament trans-épithéliale WO2014176417A1 (fr)

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US201361815329P 2013-04-24 2013-04-24
US61/815,314 2013-04-24
US61/815,329 2013-04-24
US61/815,306 2013-04-24

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Cited By (4)

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Publication number Priority date Publication date Assignee Title
WO2017135948A1 (fr) * 2016-02-03 2017-08-10 Greenspan Michael H Composition topique et système d'administration et son utilisation
US10265283B2 (en) 2012-12-07 2019-04-23 Sambria Pharmaceuticals, Llc Topical composition and delivery system and its use
US10391074B2 (en) 2012-12-07 2019-08-27 Sambria Pharmaceuticals, Llc Topical preparation for pain relief
US20220054473A1 (en) * 2019-04-22 2022-02-24 Starton Therapeutics, Inc. Continuous Delivery of Lenalidomide and Other Immunomodulatory Agents

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US10265283B2 (en) 2012-12-07 2019-04-23 Sambria Pharmaceuticals, Llc Topical composition and delivery system and its use
US10391074B2 (en) 2012-12-07 2019-08-27 Sambria Pharmaceuticals, Llc Topical preparation for pain relief
US11026902B2 (en) 2012-12-07 2021-06-08 Sambria Pharmaceuticals, Llc Topical composition and delivery system and its use
US11771669B2 (en) 2012-12-07 2023-10-03 Sbg Medical Technologies, Inc. Topical composition and delivery system and its use
WO2017135948A1 (fr) * 2016-02-03 2017-08-10 Greenspan Michael H Composition topique et système d'administration et son utilisation
GB2564026A (en) * 2016-02-03 2019-01-02 Harvey Greenspan Michael Topical composition and delivery system and its use
GB2600651A (en) * 2016-02-03 2022-05-04 Sbg Medical Tech Inc Topical composition and delivery system and its use
GB2564026B (en) * 2016-02-03 2022-07-13 Sbg Medical Tech Inc Topical composition and delivery system and its use
US20220054473A1 (en) * 2019-04-22 2022-02-24 Starton Therapeutics, Inc. Continuous Delivery of Lenalidomide and Other Immunomodulatory Agents

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