WO2005051365A1 - Composition et dispositif pour faciliter une ponction veineuse - Google Patents

Composition et dispositif pour faciliter une ponction veineuse Download PDF

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Publication number
WO2005051365A1
WO2005051365A1 PCT/EP2004/013425 EP2004013425W WO2005051365A1 WO 2005051365 A1 WO2005051365 A1 WO 2005051365A1 EP 2004013425 W EP2004013425 W EP 2004013425W WO 2005051365 A1 WO2005051365 A1 WO 2005051365A1
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WIPO (PCT)
Prior art keywords
acid
application
venipuncture
substances
skin
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Application number
PCT/EP2004/013425
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English (en)
Inventor
Carlo Ghisalberti
Mauro Marangoni
Original Assignee
Medis S.R.L.
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Publication of WO2005051365A1 publication Critical patent/WO2005051365A1/fr

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Classifications

    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • 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
    • A61K9/7007—Drug-containing films, membranes or sheets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the invention relates to a device for external use designed to improve visualisation of the veins and facilitate venipuncture in infusion and blood sampling operations, which said device contains one or more substances that highlight the venous system and have no side effects, particularly with a significant survival of the epidermal nerve fibers (ENFs) in the area of application.
  • the invention also relates to a method for highlighting and visualising the subcutaneous venoarterial structure, thus facilitating the performance of intravenous injection (i.v.), infusion and blood sampling in subjects in whom the injection site cannot easily be located using substances with a low toxicological impact. Difficulty in locating the vein at the time of venipuncture is common, and is due to the characteristics of the circulatory and muscle structure and the skin structure of each individual.
  • a venous system that is hard to locate from the outside is found in subjects who have poor muscle tone and/or are overweight and/or have a thick skin, which may be subject to natural aging processes or aging processes accelerated by environmental factors (typically "skin photoaging").
  • skin photoaging typically "skin photoaging”
  • the combination of these factors can produce a subcutaneous vein lattice that is particularly difficult to visualise, even using a tourniquet, which increases the local vein pressure. Under these conditions the operator is in difficulty and can cause problems to the patient subjected to venipuncture during blood sampling, injection of drugs, parenteral nutrition or the administration of various substances (e.g. contrast media).
  • This device substantially consists of a hydroalcoholic solution containing a fluid extract of capsicum.
  • the device contains a combination of other natural extracts which potentially improve the required performance.
  • the additional benefits claimed include an anaesthetising action and a disinfectant action by ethyl alcohol.
  • a number of patients present low tolerance to the action of capsaicin, the active constituent of capsicum. These patients experience a prolonged stinging sensation.
  • the device consists of the following components: a) one or more substances with a selective vasodilation and/or vasoactive and/or local muscle-relaxant and/or astringent and/or local muscle-relaxant effect, b) a fluid vehicle able to dissolve/disperse substances (a), and possibly other dermatologically acceptable ingredients; c) an apparatus able to apply and cause the local action of an effective quantity of (a)+(b) in the area destined for venipuncture; wherein substances (a) are characterised by a low risk of toxicity, irritation and chronic desensitisation behaviour in the application area and, more particularly, by non-neurotoxic effect as expressed as epidermal nerve fibers (ENFs) survival value ⁇ ENFs ⁇ 85% after 2 week of repeated applications.
  • ENFs epidermal nerve fibers
  • Solution or dispersion (a)+(b) may take various liquid and fluid forms, including hydroalcoholic solutions, gels, emulsions, creams, ointments, etc.. These substances can be contained in a dispensing container.
  • the device is called a "two-component" system, because (c) consists of a dispensing container which is separate from the application/rubbing medium.
  • the dispensing container may be of various types, such as a spray container, bottle with dropper, bottle of flexible material from which the contents exit under pressure, jar, tube, or a any other container which allows application to the skin and/or to the application/rubbing medium of a quantity of (a)+(b) generally ranging between 0.3 and 3 ml.
  • the application/rubbing medium could be enclosed in the pack or available at the user's premises.
  • it could be a tissue, a sponge made of non-toxic elastomer material, a non-woven material (such as cotton wool) or another medium which allows the application of (a)+(b) for rubbing on the area chosen for venipuncture, such as a swab on a stick (cotton wool buds or the like), or other similar means which ensure close contact between the skin and (a)+(b).
  • the device could be a "one-component system", wherein the application/rubbing medium is embedded with solution/dispersion (a)+(b).
  • Said means could be a woven cloth, a sponge made of non-toxic elastomer material, a non-woven material (such as cotton wool) or other medium containing a quantity of (a)+(b) generally ranging between 0.3 and
  • the medium will preferably be contained in monodose sachets or packaged in other sealed forms, such as (but not limited to)
  • Fluid vehicle (b) can also be designed as a heterogeneous system, such as emulsions, suspensions, microemulsions, etc., and can benefit in this respect from the presence of cosmetic and dermatological ingredients that promote dispersion, with possible benefits in terms of applicability, increased penetration and increased efficacy.
  • Substances (a) were identified by choosing from among drugs and plant extracts with a selective vasodilating, astringent, vasokinetic and local muscle-relaxant action. It was therefore necessary to identify active constituents which could perform these functions but entailed a low risk of chronic irritation/desensitisation and significant preservation of the epidermal nerve fibers (ENFs) in the application area.
  • Substances (a) which are useful and devoid of irritant/desensitising and neurotoxic effects were identified as the following categories: catechins, bioflavonoids, coumarins, monoterpenes, plant alkaloids, ginkgolides/ginsenosides, adrenergic alkaloids, xanthophylls, non-irritant vanilloids, polyunsaturated fatty acids, alphahydroxy acids and potassium salts.
  • catechins bioflavonoids
  • coumarins monoterpenes
  • plant alkaloids ginkgolides/ginsenosides
  • adrenergic alkaloids xanthophylls
  • non-irritant vanilloids polyunsaturated fatty acids
  • alphahydroxy acids and potassium salts a selective vasodilating, astringent, vasokinetic and local muscle-relaxant action to different extents and in different proportions, as illustrated by example 1 below.
  • catechins such as tannic acid (of the ellagic or catechic type), gallic acid, oligomeric proanthocyanosides, catechin, epicatechin and the corresponding gallocatechins and gallate esters; bioflavonoids such as hesperidin, naringenin, rutin, troxerutin, diosgenin, myricetin, apigenin, quercetin, campherol and baicalein; coumarins such as khellin, visnadine, esculoside and esculetin; monoterpenes such as menthol, geraniine, beta- and alpha-pinene, camphene, beta-myrcene, limonene, cineol, camphor, linalol, bornyl acetate, terpinenol, and isoborneol monoterpenes; plant alkaloids such as vincamine, vincine, vin
  • vasodilators with a rubescent effect such as nicotinic acid, its esters and alcohols, acetylcholine, resorcinol, pyroglutamic acid, reserpine, adenine, adenosine, arginine, cinnamic acid and aldehyde, cymarin, forscolin, esculoside, yohimbin and gamma-oryzanol.
  • Synthetic vasoactive substances can be used according to this invention, provided that the dose is not such as to generate toxicity risks in topical use.
  • Non-ionic surfactants include alkoxylates of fatty acids and alcohols or of sorbitan, polyoxypropylene and polyoxyethylene, and alkyl polyglycosides; anionic surfactants include soaps of fatty acids, sodium lauryl sulphate or lauryl ether sulphate, alkyl benzene sulphonates, mono and/or dialkyl phosphates and the like; amphoteric surfactants include dialkylamine oxides, various types of betaine, phospholipids and natural ceramides.
  • a thickener can be present in the quantity of 0.1 % to 10% of a composition with an aqueous base, and preferably 0.5% to 5%.
  • thickeners are cross-linked polyacrylates (Carbopol ), and gums like xanthan, carrageenan, gelatin, karaya and pectin.
  • Emollients Another category of functional ingredients which can be included in the device according to the invention is emollients. Under some circumstances emollients perform a dual function, acting both as vehicles (facilitating the dispersion of the ingredient according to the invention) and as skin softeners. Emollients can be incorporated in the device according to the invention in the quantity of 0.5% to 50% in weight. Emollients can be classified as fatty alcohols, esters and acids, polyols and hydrocarbons. Examples of fatty diesters are dibutyl adipate, diethyl sebacate, diisopropyl dimerate, propylene glycol myristyl ether acetate, diisopropyl adipate and dioctyl succinate.
  • Examples of branched fatty esters are 2-ethyl-hexyl myristate, isopropyl stearate and isostearyl palmitate.
  • Examples of fatty triesters are triisopropyl trilinoleate, trilauryl citrate, tributyrin and saturated and unsaturated vegetable oils.
  • Examples of esters of fatty alcohols are lauryl palmitate, myristyl lactate, oleyl erucate, oleyl stearyl coco-caprylate/caprate, and cetyl octanoate.
  • Examples of linear fatty alcohols are alcohols C10-C20 such as cetyl, myristyl, palmityl and stearyl alcohols.
  • zingerone was used for non-capsaicin vanilloids
  • tannic acid (tannin) from oak was used for catechins
  • neohesperidin was used for bioflavonoids
  • Amni visnaga extract was used for coumarins
  • menthol was used for monoterpenes
  • hydroalcoholic fluid extract of Vinca minor was used for plant alkaloids
  • dried extract of Ginkgo biloba was used for ginkgolides/ginsenosides
  • dopamine was used for adrenergic alkaloids
  • pentoxyphylline was used for xanthophylls
  • polyunsaturated fatty acids obtained from saponified grape pip oil were used for polyunsaturated fatty acids
  • lactic acid (racemate) was used for alphahydroxy acids
  • potassium acetate was used for potassium salts.
  • a 2% solution in 65° ethyl alcohol in volume is generally produced for each substance. The results are illustrated in Table I. T
  • Example 3 Two-component system with W/O emulsion and application with cotton wool
  • An emulsion with a high inner phase is prepared by hot emulsifying the aqueous and oily phases of the following ingredients: Ginkgo biloba extract 12 g Adrenaline 0.2 g Fatty acids from grape pips 10 g Glycolic acid 5 g Glycerin 1 g 01eyl-(2)-POE 5 g Hydrogenated coconut oil 5 g Bentone 38 0.5 g CaS0 4 7 2 0 0.3 g Deionised water q.s. for 100 ml The emulsion is then placed in a 100 ml ceramic jar, and approx.
  • Example 4 Two-component system with emulsion in tube and application with sponge An O/W emulsion is prepared by hot emulsifying of aqueous and oily phases of the following ingredients: Menthol 1.5 g Dopamine 0.2 g Periwinkle, fluid extract 2 g Cyclomethicone 2.0 g Cetearyl alcohol + PEG-40 hydrogenated castor oil + Na cetearyl sulphate 4.5 g Octyl stearate 3.0 g Castor oil 4.0 g Glycerin 3.0 g Carbopol 0.3 g Hydroxypropyl methylcellulose 0.3 g Sodium edetate 1.5 g Preservatives q.s.
  • Example 5 One-component system with tissue embedded with alcoholic lotion A hydroalcoholic solution is prepared by dissolving the following ingredients: Tannic acid from Quercus robus 0.5 g Menthol i g Zingerone i g Periwinkle, fluid extract 2 g d,l-lactic acid, 80% in water 5 g Glycerin 2.5 g 65° ethanol volume q.s.
  • Example 6 One-component system with tissue embedded with alcoholic lotion
  • a hydroalcoholic solution is prepared by dissolving the following ingredients: Gallic acid 1 g Terpene fraction from lemon 1 g Buflomedil 0.5 g Visnadine (VisnadexTM, Indena, I) 1 g Adenosine 0.5 g Esculoside 0.5 g Glycerin 2 g 65° ethanol, volume q.s. for 100 ml 2 ml of the solution is placed in sachets containing a non-woven cellulose tissue. The sachets are then heat-sealed.
  • Gallic acid 1 g Terpene fraction from lemon 1 g Buflomedil 0.5 g Visnadine (VisnadexTM, Indena, I) 1 g Adenosine 0.5 g Esculoside 0.5 g Glycerin 2 g 65° ethanol, volume q.s. for 100 ml 2 ml of
  • Comparative example 1 One-component system with tissue embedded with an alcoholic solution of capsaicin AgavenTM tissues (Regard s.a.s., Bagnocavallo, RA, Italy), packaged in heat-sealed sachets, contain the following ingredients: Extract of Formes officinalis 12 g Extract of Avena sativa 12 g Extract of Capsicum frutescens 10 g Extract of Cratageus oxyacantha 10 g Glycerin 1 g 70° ethanol volume q.s.
  • Example 7 Test of cell survival on fibroblast culture to evaluate skin irritation potential and biocompatibility (MTT assay)
  • the key reagent is 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide or MTT, a substance which gives a yellow colour in aqueous solution.
  • the mitochondrial dehydrogenase of the viable cells splits the tetrazole ring, leading to the formation of purple-violet formazan crystals which are insoluble in water.
  • the crystals are dissolved in acidified isopropanol, and the resulting violet solution is measured spectrophoto metrically.
  • the test is conducted with the solution described in example 5. Under the test dilution conditions, the irritant power demonstrates the skin compatibility of the device according to the invention.
  • Example 8 Occlusive application test for clinical evaluation of irritant, allergenic and sensitising effects (patch test)
  • An increase or reduction in viable cells leads to a concomitant change in the quantity of formazan formed, which can be considered as an indicator of the degree of cytotoxicity caused by exposure to irritant substances.
  • This test enables the tolerability of a cosmetic product to be evaluated by identifying and classifying its potential irritant power, and at a preliminary level, identifying its potential sensitising power.
  • the device will be applied to volunteers using "Finn Chambers", 7 mm diameter aluminium discs containing absorbent paper discs soaked in a known quantity of test sample.
  • Ten-healthy symptom-free volunteers enrolled after neurological examination of the peripheral nervous system and chack of the motor (ulnar, median, peroneal and tibial) and sensory (median and sural) nerve conduction normality are instruicted to apply the device of Example 7 (B) or the capsaicin-containing device (AgavenTM, by Regard s.a.s., Bagnocavallo, RA, Italy) (C) four times daily for 2 weeks onto ea two separate 15 cm 2 area on the inner arm or volar forearm with vigorously applications.
  • Skin blisters can be made by applying a suction capsule (W.R. Medical Electronics, Stillwater, MN) with double sided tape to cleansed, shaved skin.
  • the surface of the capsule resting on skin contained a 3-mm diameter opening.
  • the capsule can be secured to skin with an elastic bandage, the area warmed with a heating pad and the capsule evacuated to a negative pressure of 300 mm Hg. After a full blister had formed the capsule can be removed immediately to prevent overstretching.
  • the blister roof can be excised with a microscissors, flattened between two microscope slides in a drop of cold Zamboni's fixative for approximately 10 min, placed in cold Zamboni's solution overnight, then cryoprotected with 20% sucrose in 0.1 M phosphate buffered saline (PBS) until processed.
  • PBS phosphate buffered saline
  • the whole blister roof can be frozen, then double immunostained to visualize ENFs using antibodies to the pan-neuronal marker protein gene product 9.5 (PGP 9.5, rabbit polyclonal) and to Langerhans cells using antibody to CD- la (mouse monoclonal) then reacted with secondary antibodies conjugated with cyanine 2, 3 or 5 fluorescent probes (Jackson Immunoresearch, West Grove, PA).
  • PPP 9.5 pan-neuronal marker protein gene product 9.5
  • CD- la mouse monoclonal
  • cyanine 2, 3 or 5 fluorescent probes Jackson Immunoresearch, West Grove, PA.
  • Skin biopsies obtained with a 3-mm punch following local anesthesia lidocaine (1%) anesthesia can be fixed overnight in Zamboni's solution and then cryoprotected with 20% sucrose in 0.1 M PBS. Frozen sections, 100 mm thick, can processed for immunofluorescent localization of the antigens listed in Table 1 with cyanine 2, 3, and 5.
  • ENFs in biopsies can be quantified as described (Kennedy, W.R., Wendelschafer-Crabb, G. and Johnson, T., Neurology, 47 (1996) 1042-1048.). Briefly, digitized confocal images of immunostained nerves in the epidermis can be traced using Neurolucida software (Micro-BrightField, Colchester, VT). Counts of nerve fibers in epidermis can be derived from the number of fibers crossing the dermal-epidermal basement membrane. ENFs can be expressed as fibers/mm length of section.
  • ENFs/mm biopsy 39 35 89.7% 22 56.4% (A) skin biopsy prior to treatment; (B) skin biopsy after 2 weeks of application of capsaicin-containing device; ⁇ BNFs (B) percent survival of epidermal nerve fibers (ENFs) of (B) compared to control (A); (C) skin biopsy after 2 weeks of application of capsaicin-free device; ⁇ ENFs (C) percent survival of epidermal nerve fibers (ENFs) of (C) compared to control (A).
  • Samples (B) contained dermal PGP 9.5-ir bundles of unmyelinated nerves that ascended and branched to form an extensive subepidermal neural plexus (SNP) in the papillary dermis, before single nerve fibers crossed the dermal- epidermal junction to ascend in the epidermis which closely resembled those of samples (A).
  • Substance P (SP) and calcitonin gene related peptide (CGRP) containing fibers were present in the nerve trunks and the SNP but seldom entered the epidermis.
  • Examination of cutaneous innervation by immunolocalization of the PGP 9.5 of samples (C) revealed a striking loss of nerve fibers after 2 weeks.
  • the device according to the invention produce a neurotoxicity effect misurated on the epidermal nerve fibers (ENFs) survival which is consistent with the non-toxic behaviour required. More particularly the inventive device is devoid of significant neurotoxicity behaviour.

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  • Health & Medical Sciences (AREA)
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  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract

L'invention concerne un dispositif à usage externe servant à localiser les veines sous-cutanées afin de faciliter une ponction veineuse. Le dispositif selon l'invention contient des substances mettant en évidence le système veineux sans endommager la zone d'application cutanée.
PCT/EP2004/013425 2003-11-27 2004-11-26 Composition et dispositif pour faciliter une ponction veineuse WO2005051365A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI2003A02322 2003-11-27
IT002322A ITMI20032322A1 (it) 2003-11-27 2003-11-27 Dispositivo atossico per facilitare la venipuntura.

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WO2005051365A1 true WO2005051365A1 (fr) 2005-06-09

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006104564A1 (fr) * 2005-03-28 2006-10-05 Kimberly-Clark Worldwide, Inc. Procede de prevention et/ou de traitement d'infections vaginales et vulvaires
WO2010034019A1 (fr) * 2008-09-22 2010-03-25 Biochemics, Inc. Administration transdermique de médicaments employant un osmolyte et un agent vasoactif
US7786176B2 (en) 2005-07-29 2010-08-31 Kimberly-Clark Worldwide, Inc. Vaginal treatment composition containing xylitol
US9278233B2 (en) 2008-12-04 2016-03-08 Biochemics, Inc. Methods and compositions for tattoo removal

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1249406B (it) * 1991-06-04 1995-02-23 Arrigo Cavallini Sostanza atta ad evidenziare le vene superficiali, ad azione anestetica locale da aggiungere ai disinfettanti per cute per facilitare la venipuntura
WO1997013483A1 (fr) * 1995-10-11 1997-04-17 Godfrey Marjorie M Dispositif pour appliquer un anesthesique local
WO1997013482A1 (fr) * 1995-10-12 1997-04-17 Masiz John J Systeme moleculaire d'administration transdermique
WO2001054679A2 (fr) * 2000-01-27 2001-08-02 Children's Hospital Research Foundation Composition d'anesthesique et de vasodilatateur transdermique et procedes pour son administration topique
US20020197284A1 (en) * 1999-12-16 2002-12-26 Luo Eric C. Transdermal and topical administration of local anesthetic agents using basic enhancers

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1249406B (it) * 1991-06-04 1995-02-23 Arrigo Cavallini Sostanza atta ad evidenziare le vene superficiali, ad azione anestetica locale da aggiungere ai disinfettanti per cute per facilitare la venipuntura
WO1997013483A1 (fr) * 1995-10-11 1997-04-17 Godfrey Marjorie M Dispositif pour appliquer un anesthesique local
WO1997013482A1 (fr) * 1995-10-12 1997-04-17 Masiz John J Systeme moleculaire d'administration transdermique
US20020197284A1 (en) * 1999-12-16 2002-12-26 Luo Eric C. Transdermal and topical administration of local anesthetic agents using basic enhancers
WO2001054679A2 (fr) * 2000-01-27 2001-08-02 Children's Hospital Research Foundation Composition d'anesthesique et de vasodilatateur transdermique et procedes pour son administration topique

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006104564A1 (fr) * 2005-03-28 2006-10-05 Kimberly-Clark Worldwide, Inc. Procede de prevention et/ou de traitement d'infections vaginales et vulvaires
AU2006229642B2 (en) * 2005-03-28 2011-07-14 Kimberly-Clark Worldwide, Inc. A method for preventing and/or treating vaginal and vulval infections
US7786176B2 (en) 2005-07-29 2010-08-31 Kimberly-Clark Worldwide, Inc. Vaginal treatment composition containing xylitol
WO2010034019A1 (fr) * 2008-09-22 2010-03-25 Biochemics, Inc. Administration transdermique de médicaments employant un osmolyte et un agent vasoactif
US9566256B2 (en) 2008-09-22 2017-02-14 Biochemics, Inc. Transdermal drug delivery using an osmolyte and vasoactive agent
US10537536B2 (en) 2008-09-22 2020-01-21 Biochemics, Inc. Transdermal drug delivery using an osmolyte and vasoactive agent
US10751309B2 (en) 2008-09-22 2020-08-25 Biochemics, Inc. Transdermal drug delivery using an osmolyte and vasoactive agent
US9278233B2 (en) 2008-12-04 2016-03-08 Biochemics, Inc. Methods and compositions for tattoo removal
US10322077B2 (en) 2008-12-04 2019-06-18 Biochemics, Inc. Methods and compositions for tattoo removal

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