WO2015021954A1 - Aerosol dispenser for transdermally acting pharmaceutical compositions - Google Patents

Abstract

The invention relates to an aerosol dispenser (1) for administering transdermally acting pharmaceutical active ingredients, comprising a vessel (3) that contains the pharmaceutical active ingredient in a liquid solution (2), the interior (4) of which vessel is under pressure by means of a propellant gas or the interior (4) of which vessel can be pressurized by means of a pumping device (5), an atomizing device (6) connected to the interior (4) of the vessel (3), and an actuatable dispensing valve (7) arranged between the interior (4) of the vessel (3) and the atomizing device (6). The invention is characterized in that a placement hood (9) is provided, which has a container opening (10), which can be placed onto the container (3), and that the placement hood (9) has an administration opening (11) having a placement lip (12) for placing the placement hood (9) onto the skin. The invention further relates to uses of such an aerosol dispenser (1).

Description

 Aerosol dispenser for transdermal acting pharmaceutical

 compositions

Field of the invention

The invention relates to an aerosol dispenser for

Application of transdermally acting pharmaceutical agents or compositions, with a den

pharmaceutical agent in a liquid solution containing vessel, the interior of which by means of a

Propellant gas is under pressure or the interior of which can be placed under pressure by means of a pumping device, with a connected to the interior of the vessel

Sputtering device, with an arranged between the interior of the vessel and the sputtering device actuatable dispensing valve, and with a with the

Dispensing valve associated spray head, as well as uses of such an aerosol dispenser.

Background of the invention and prior art

Aerosol dispensers for inhalation are widely known, for which only reference is made, for example, to the publications EP 0 227 510 Bl and EP 1 545 670 Bl. Such

Aerosol dispensers typically comprise a pressurized or pressurizable vessel containing the active ingredient composition to be inhaled, usually in solution. About a dispensing valve and a

 Atomizing device becomes the active ingredient composition

| Confirmation copy | aerosolized and released. Typically, such an aerosol dispenser comprises a mouthpiece or nosepiece which is inserted in the mouth or nose prior to actuation of the mouthpiece or nosepiece

Dispensing valve is to be introduced. Simultaneously with the actuation of the delivery valve, the patient must breathe in to take the

Inhalation of the active ingredient composition.

In particular, the latter is difficult to perform sufficiently synchronously for the patient, so that often a large part of the active ingredient composition does not reach the inner respiratory tract and is thus lost.

Another dosage form of

 Active ingredient compositions include the so-called

transdermal systems. Here is the

Active ingredient composition applied to the skin of a human or animal and resorbed more or less rapidly depending on the design of the transdermal system. The

Active ingredients can act locally or systemically.

Advantages of transdermal administration over the

Inhalation or even oral administration include better tolerability, localized drug targeting, controlled absorption rates and thus avoidance of reduced bioavailability of the drug. Transdermal systems can be formed, for example, as an adhesive patch, ie in the core consist of a sticker to be stuck to the skin, which is a substrate in or on which the active ingredient composition

is arranged, and comprises an adhesive layer through which the active ingredient composition by permeation reaches the skin and is absorbed there. An example here is a nicotine patch according to WO2000 / 033812 A. Such patches are disadvantageous because they visually interfere and also develop problems in terms of water resistance and secure adhesive attachment to the skin with the result of reduced drug absorption by the patient, in particular the result of impaired controllability of the Bioavailability of the drug over the given treatment period. However, coatings on the skin are also referred to as a patch, which are sprayed onto a target surface of the skin as an aerosol and form a coating adhering to the target surface. Typically, the aerosol compositions contain a film-forming polymer as a matrix which forms the actual patch, as well as an active ingredient composition which is embedded in the matrix as it is sprayed onto the skin. The

Polymer of the matrix is selected and

designed so that the delivery rate of the drug is adapted to the skin of a preset. Most includes the

 The aerosol composition also includes at least one solvent, typically a volatile, pharmacologically acceptable and solvent-compatible and polymer-compatible organic solvent. Sometimes the aerosol also contains a propellant, for example if the aerosol dispenser is designed as a spray bottle. The propellant can also act as a solvent

function. An example of a composition for spraying to form a patch is described in WO 2001/037890. Aerosol compositions for the formation of transdermal patches are typically of a classical type

Spray applied, the spray can is kept at a predetermined distance from the skin, with the

Sputtering device directed to the skin, and then the dispensing valve is actuated for a predetermined time. However, this is disadvantageous in several respects. First, it should be noted that aerosol compositions for patches are relatively expensive to manufacture, in addition to the

Active substance is also a tailor-made polymer for the purpose of film formation and as a depot for the active ingredient to develop and manufacture. At the classic

Spraying, as described above, however, a significant portion of the aerosol is lost. This begins with the fact that an operator can not see the direction of the spray safely and usually first takes a spray attempt. Furthermore, a part of the spray does not strike the target area of the skin, but rather undesired neighboring areas (skin and / or clothing) or even quite next to the person. Furthermore, there is a risk that a part of the spray mist by the operator or third persons is inhaled undesirably.

Finally, there is a risk of contamination of the

Environment with the active substance, for example, only for example, the increased steroid levels in groundwater of cities is pointed out.

Technical problem of the invention The invention is therefore the technical problem

Basically, an aerosol dispenser for the application

indicate transdermal drug compositions, which on the one hand a loss more expensive

On the other hand reduces the composition of active ingredients and on the other hand reduces the risk of contamination of adjacent skin areas of the patient, the skin of a third person, or the environment by unwanted drug administration, but in particular reliably avoids the unwanted inhalation of the transdermal drug composition by persons.

Broad features of the invention and preferred embodiments

To solve this technical problem, the invention teaches an aerosol dispenser for the application of transdermal acting pharmaceutical agents, containing a pharmaceutical agent in a liquid solution containing vessel whose interior by means of a

 Propellant gas is under pressure or the interior of which can be placed under pressure by means of a pumping device, with a connected to the interior of the vessel

Sputtering device, comprising an operable dispensing valve disposed between the interior of the vessel and the sputtering device, having a spray head connected to the dispensing valve, a spout

is furnished, which has a container opening, which is placed on the container and wherein the

Aufsetzhaube an application opening with a Aufsetzlippe for placing the Aufsetzhaube has on the skin.

The term aerosol is to be understood in the context of the invention. These are to be understood as meaning spray sprays with an average droplet size of up to 0.1 mm and more.

With the invention it is achieved that upon actuation of the dispensing valve, the interior of the attachment cap is filled with the patch forming aerosol or spray, the atomizer device preferably directs the aerosol beam in the direction of the Aufsetzlippe, ie. the

Sputtering device has an outlet opening which points in the direction of the Aufsetzlippe ^' . The fact that the attachment hood with the container opening to the vessel and with the Aufsetzlippe the skin is virtually tight, the aerosol can not leave this interior of the attachment hood. Contamination of adjacent skin areas, clothing, third persons or the environment can not take place. In particular, unwanted inhalation of the aerosol is excluded. In addition, a patch with a defined circumference is formed by the edge of the placement lip, wherein, in addition, the thickness of the patch is formed almost homogeneously over the surface of the patch thus formed.

 This achieves a particularly well-defined kinetics of drug delivery to the skin and consequently a very readily controllable bioavailability of the active ingredient. In the following, preferred embodiments of the

Invention explained. In principle, the attachment hood can be formed from any medically compatible material.

Preferably, an organic polymer is used, for example a thermoplastic, e.g. Polyolefins such as PE or PP, or a thermoplastic elastomer as indicated below. It is preferred if at least the Aufsetzlippe or Aufsetzhaube is formed entirely from one or more different rubber-elastic material. These include, for example, natural rubber, modified natural rubber, silicone rubber, EPDM, olefin-based thermoplastic elastomers such as PP / EPDM, urethane-based thermoplastic elastomers,

thermoplastic polyester elastomers or copolyesters, styrene block polymers such as SBS, SEBS, SEPS, SEEPS, or MBS, and thermoplastic copolyamides, such as PEBAX.

The Aufsetzhaube may have in the field of Aufsetzlippe a shape that is suitable for complete investment in a target area on the skin. While are

In principle, many such forms conceivable, but should be useful training, which has circular or oval ring shape in cross section. Preferably, the cross-sectional area of the Aufsetzlippe is greater than the cross-sectional area of the container opening, ie the Aufsetzhaube widens from the container opening to Aufsetzlippe out. In this case, the Aufsetzhaube formed with a substantially conical shell surface, with in cross section in the plane of the Central axis of the cone of straight, convex or concave conical surface.

It will be useful if the Aufsetzhaube in the field of Aufsetzlippe has a lower hardness than in the

Area outside the Aufsetzlippe. For example, the landing lip may have a Shore A hardness of up to 10, while the landing hood may otherwise have a Shore A hardness of 20, especially 40, up to 120 and more.

The attachment hood can be firmly or reversibly connectable to the vessel. In the former case, the Aufsetzhaube is connected in the manufacture of the aerosol dispenser with the vessel, by positive engagement, adhesion or

Fabric connection. It is then non-destructive

removable. In the latter case, vessel and

Aufsetzhaube be provided separately to the operator, which then the Aufsetzhaube,

for example via a clamp connection or a

Latching connection, touches on the vessel and possibly also decreases again, for example, a space-saving

Allow storage of the aerosol dispenser.

If the atomizing device has an outlet opening which points in the direction of the Aufsetzlippe, it is ensured that the majority of the aerosol reaches the skin and only a small part is reflected on the inner wall of the Aufsetzhaube and so

get lost . The cross sections of the container opening and the

Application ports may be oriented parallel to one another or angled relative to each other, i.e. the attachment hood can also have an angle piece in the region of the container opening.

An aerosol dispenser according to the invention typically contains a solution in the vessel with the following components: a) A physiologically compatible organic or aqueous solvent, for example organic solvents which are volatile at a skin temperature of about 35 ° C.

Benzyl alcohol, ethanol, methanol, propanol, isopropanol, butanol, isobutanol, diacetone alcohol, methylene chloride, carbon tetrachloride, trichlorethylene, chlorothene, ethyl acetate, n-propyl acetate, n-butyl acetate,

Isobutyl acetate, amyl acetate, duPont DBE, Exxate 500, 700, 900, glycol and ether / ester derivatives, ethylene glycol, PM acetates, butyl cellosolve, carbitol acetate,

Butylcarbitol acetate, Ektapro EEP, toluene, xylene, VM & P naphtha, mineral solvents, Aromatic 100, Aromatic 150, acetone, methyl ethyl ketone, methyl butyl ketone,

Dimethyl ether, benzyl benzoates, isopropyl myristate,

Acetonitrile, ethyl oleates, glycerol, glycofurol

(tetraglycol), propylene glycol, polyethylene glycol (PEG), hexane, n-hexane, glycol ether, methylene chloride,

Methyl chloride, octyldodecanol, trichloroethane

Diethyl phthalate and dibutyl phthalate. b) a transdermally active pharmaceutical agent, for example: antidiarrhoeal agents, such as diphenoxylates, Loperamides and Hyoscyamine; Cardiovascular agents such as Hydralazine, Minoxidil, Captopril, Enalapril, Clonidine, Prazosin, Debrisoquine, Diazoxide, Guanethidne,

Methyldopa, reserpine, trimetaphan, diltiazem, felodopine, amlodipine, nitrendipine, nifedipine and verapamil,

Amiodarone, flecainide, disopyramide, procainamide,

Mexiletenes, quinidine, glyceryl trinitrates,

Erythritol tetranitrate, pentaerythritol tetranitrate,

Mannitol hexanitrates, perhexilene, isosorbide dinitrates, nicorandil, alprenolol, atenolol, bupranolol, carteolol, labetalol, metoprolol, nadolol, nadoxolol, oxprenolol, pindolol, propranolol, sotalol, timolol and

Timolol maleates, digoxin, adrenaline, ephedrine, fenoterol, isoprenaline, orciprenaline, rimeterol, salbutamol,

Salmeterol, terbutaline, dobutambe, phenylephrine,

Phenylpropanolamines, pseudoephedrines, dopamine,

Cyclandelates, isoxsuprines, papaverines, dipyrimadoles,

Isosorbide dinitrates, phentolamine, nicotinyl alcohol, co-dergocrine, nicotinic acid, glyceryl trinitrates,

Pentaerythritol tetranitrate, xanthine, ergotamine,

Dihydroergotamine, Methysergide, Pizotifen and

sumatriptan; Anticoagulants and thrombolytic agents such as warfarin, dicoumarol, low molecular weight heparins such as noxaparin, plasminogen activators such as streptokinase, t-pA, and hemostatic agents such as aprotinin, tranexamic acid and protamines; CNS agents, such as buprenorphins,

Dextromoramide, Dextropropoxyphene, Fentanyl, Alfentanil, Sufentarlil, Hydromorphone, Methadone, Morphine,

Oxycodone, Papaveretum, Pentazocine, Pethidine,

Phenoperidine, codeine, dihydrocodeine, acetylsalicylic acid (ASA), paracetamol, phenazone, barbiturates, Amylobarbitones, butobarbitones, pentobarbitones,

Choral hydrates, chlormethiazoles, hydroxyzines, meprobamates, benzodiazepines, alprazolam, bromazepam, chlordiazepoxides, clobazam, chlorazepates, diazepam, flunitrazepam,

Flurazepam, lorazepam, nitrazepam, oxazepam, temazepam, triazolam, phenothiazines, chlorpromazine, fluphenazine, pericyazine, perphenazine, promazine, thiopropazate,

Thioridazine and trifluoperazine, butyrophenones,

Droperidol, haloperidol, pimozide, thiothixene, lithium, tricyclic antidepressants, amitryptyline, clomipramine, desipramine, dothiepin, doxepin, imipramine,

Nortriptytine, Opipramol, Protriptyline, Trimipramine, Tetracyclic Antidepressants, Mianserin, Monoamine Oxidase Inhibitors, Isocarboxazid, Phenelizine, Tranylcy romine, Moclobemide, Fluoxetine, Paroxetine, Citalopram,

 Fluvoxamine, sertraline, caffeine, tacrine, amantadine, benserazide, carbidopa, levodopa, benztropine, biperiden, benzhexol, procyclidine, S (-) -2- (N-propyl-N-2-thienylethylamino) -5-hydroxytetralin (N-0923 ), Phenytoin, valproic acid, primidone, phenobarbitone,

 Methylphenobarbitones, carbamazepines, ethosuximides,

Methsimides, Phensuximides, Sulthiams, Clonazepam,

Phenothiazines, Prochloperazine, Thiethylperazine,

Ondansetron, granisetron, dimenhydrinate, diphenhydramine, metoclopramide, domperidone, hyoscine,

 Hyoscine Hydrobromide, Hyoscine Hydrochloride, Clebopride, Compride; Anti-inflammatory agents, such as ibuprofen, flurbiprofen, ketoprofen, aclofenac, diclofenac,

Aloxiprine, Aproxene, Diflunisal, Fenoprofen, Indomethacin, Mefenarnic Acid, Naproxen, Phenylbutazone, Piroxicam, Salicylamide, Salicylic Acid, Sulindac, Desoxysulindac, Tenoxicam, tramadol, ketalacal, flufenisal, salsalates, triethanolamine salicylates, aminopyrins, antipyrins,

Oxyphenbutazone, Apazone, Cintazone, Flufenamie Acid, Clonixeril, Clonixin, Eclofenarnie Acid, Flunixin,

Colchicine, demecolcine, allopurinol, oxypurinol,

 Benzydamine hydrochlorides, dimefadans, indoxoles, intrazoles, imbaehydrochlorides, paranylene hydrochlorides,

Tetrydamine, benzindopyrine hydrochloride, fluprofen, ibufenac, naproxol, fenbufen, cinchophen, diflumidone sodium, fenamole, flutiazine, etazamide,

 Letimidehydrochloride, Nexeridine hydrochloride,

Octazamides, olinazoles, neocinchophen, nimazoles,

Proxazolecitrates, Tesicam, Tesimide, Tolmetin,

Triflumidale, penicillamine, aurothioglucose, sodium aurothiomalate, ethotrexate, aurofm, baclofen,

Diazepam, Cyclobenzaprine Hydrochloride, Dantrolene,

 ethocarbamol, orphenadrins, quinine, allopurinol,

Colchicine, probenecid and sulphinpyrazone; Hormones, steroids and steroidal substances, such as oestradiol,

Oestriol, Oestrone, Ethinyloestradiol, estranol,

 Stilboestrol, dienoestrol, epioestriol, estropipate and zeranol, allyloestrenol, dydrgesterone, lynoestrenol, norgestrel, norethyndrel, norethisterone, norethisterone acetate, gestodene, levonorgestrel, edroxyprogesterone, egestrole, cyproterone acetate, danazol, epitestanol, exemestane, 4-hydroxy-androstenedione, testosterone, ethyltestosterone, Clostebol acetate, Drostanolone, Furazabol, Nandroloneoxandrolone, Stanozolol,

Trenbolone acetates, Dihydrotestosterone, 17-alpha-ethyl-19-nortestosterone, Fluoxymesterone, Finasteride,

Turosterides, LY-191704, K-306, Betamethasone, Betamethasone valerates, Cortisone, Dexamethasone,

Dexamethasone 21 -phosphate, fludrocortisone,

Flumethasone, fluocinonide, fluocinonide desonide,

Fluocinolones, Fluocinolones acetonide, Fluocortolone, Halcinonide, Halopredone, Hydrocortisone, Hydrocortisone 17-valerate, Hydrocortisone 17-butyrate, Hydrocortisone 21-acetate Methylprednisolone, Prednisolone, Prednisolone 21-phosphate, Prednisone, Triamcinolone, Triamcinolone acetonide, Cortodoxone, Fluoracetonide, Fludrocortisone, Difluorsonediacetate , Fluorandrenolone acetonides,

Medrysone, Arncinafel, Amcinafide, Betamethasone,

Chloroprednisone, Clorcortelone, Descinolone, Desonide, Dichlorisone, Difluprednate, Flucloronide, Flumethasone, Flumololide, Flucortolone, Fluoromethalone, Fluperolone, Fluprednisolone, Meprednisone, Methylmeprednisolone, Paramethasone, Cortisone acetate, Hydrocortisone

cyclopentylpropionate, cortodoxone, flucononide,

Fludrocortisone acetate, flurandrenolone acetonide,

Medrysone, Amcinafal, Amcinafde, Betamethasone,

Betamethasone benzoate, chloroprednisone acetate,

Clocortolone acetate, Descinolone acetonide,

Desoximetasone, dichloroisone acetate, difluprednate, flucloronide, flumethasone pivalate, flunisolide acetate, fluperolone acetate, fluprednisolone valerate,

Paramethasone acetate, Prednisolamate, Prednival,

 Triamcinolone hexacetonide, cortivazole, formocortal, nivazole, corticotrophin, thyrotrophin, follicle stimulating hormone (FSH), luteinizing hormone (LH), gonadotrophin releasing hormone (GnRH), insulin, chlorpropamide,

Glibenclamide, gliclazide, glipizide, tolazarnide,

Tolbutamide and metformin, calcitonm, thyroxine, Liothyronine, Carbimazole, Propylthiouracil, Octreotide, Bromocriptine, Clomiphene; Diuretics and antidiuretics, such as thiazides, bendrofluazides, chlorothiazides,

Chlorthalidones, dopamine, cyclopenthiazides,

Hydrochlorothiazide, indapamide, mefruside,

 Meiycholthiazide, Metolazone, Quinethazone, Bumetanide, Ethacrynic Acid, Frusemide, Spironolactone, Amiloride, Triamterene, Desmopressin, Lypressin An, Vasopressin, Ergometrine, Oxytocin, Gemeprost, Prostaglandins,

Alprostadil (PGE1), Prostacyclin (PGI2), Dinoprost

 (Prostaglandin F2-alpha), misoprostol; antimicrobial, antifungal or antiseptic agents, such as cephalosporins, cephalexin, cefoxytin, cephalothin, penicillins,

Amoxycillin, amoxycillin + clavulanic acid, ampicillin, bacampicillin, benzathine penicillin, benzylpenicillin, carbenicillin, cloxacillin, methicillin, phenethicillin, phenoxymethylpenicillin, flueloxacillin, mezlocillin, piperacillin, ticarcillin, azlocillin, tetracyclines, minocycline, chlortetracycline, demeclocycine,

Doxycycline, Methaeycline, Oxytetracycline, Amikacin,

Gentamicin, kanamycin, neomycin, netilmicin, tobramycin, amorolfine, isoconazole, clotrimazole, econazole,

miconazole, nystatin, terbinafine, bifonazole,

Amphotericin, Griseofulvin, Ketoconazole, Fluconazole, Flucytosine, Fezatione, Ticlatone, Tolnaftate, Triacetin, Zinc, Pyrithione, Sodium pyrithione, Quinolone, Nalidixic acid, Cinoxacin, Ciprofloxacin, Enoxacin, Norfloxacin, Sulphonamides, Phthalylsulphthiazoles, Sulfadoxines,

Sulphadiazines, Sulphamethizole, Sulphamethoxazoles,

Sulphone, dapsone, chloramphenicol, clindamycin,

Erythromycin, erythromycin ethyl carbonate, erythromycin estolate, erythromycin glucepate, erythromycin

ethyl succinate, erythromycin lactobionate, roxithromycin, lincomycin, natamycin, nitrofurantoin, spectinomycin, vancomycin, aztreonam, colistin IV, metronidazole,

Tinidazole, fusidic acid, trimethoprim, 2-thiopyridine N-oxide, iodine-PVP complex, diiodohydroxyquin,

Hexachlorophenes, chlorhexidines, chloroamines,

Benzoyl peroxides, ethambutol, isoniazid, pyrazinamides.

Rifampicin, clofazimines, primaquine, pyrimethamine,

Chloroquine, hydroxychloroquine, quinine, mefloquine,

Halofantrines, acyclovir, acyclovir prodrugs, famciclovir, zidovudine, didanosinc, stavudine, lamivudine,

Zalcitabine, saquinavir, indinavir, ritonavir, n-docosanol, tromantadine, idoxuridine, mebendazole,

Thiabendazole, niclosamide, praziquantel, pyrantel

embonate, diethylcarbamazine, plicamycin,

 Cyclophosphamide, dacarbazine. Fluorouracil, procarbazine, 6-mercaptopurine, mucophenolic acid, alcohols, ethanol, isopropanol, quaternary ammonium compounds,

Benzalkonium Chloride, Detrimide, Cetypyridinium Chloride, Bisdequalinium Diacetate, Dequalinium Chloride,

Chlorhexidine, chlorhexidine acetate, PMMB; Chloramines, sodium dichloroisocyanate, sodium hypochlorite;

Substances for metabolism, such as dexfenfluramine, fenfluramine diethylpropion, mazindol, phentermine, calcitriol,

 Dihydrotachysterol; Active substances for the immune system, such as meclozine, cyclizines, chlorcyclizines, hydroxyzines,

Bromopheniramine, chlorpheniramine, clemastine,

Cyproheptadine, Dexchlorpheniraraine, Diphenhydramine, Diphenylamine, Doxylamine, Mebhydroline, Mepyramine,

Phenirarnines, tripolidines, azatadines, diphenylpyralines, Methdilazine, terfenadine, astemizole, loratidine,

Cetirizine; Immunomodulators, such as tacrolimus, sirolimus or pimecrolimus; Anesthetics, such as bupivacaine,

Amethocaine, lignocaine, cinchocaine, dibucaine,

Mepivacaine, prilocaine, etidocaine; Neuromusculäre

Blockers such as suxamethonium, alcuronium, pancuronium, atracurium, gallamine, tubocurarine, vecuronium;

Smoking article substitutes, such as nicotine, bupropion,

ibogaine; dermatological agents, such as vitamin A, vitamin D, vitamin E, vitamin E acetate, vitamin E sorbate;

 Terpenoids or essential oils, allergens for desensitization, such as pollen or house dust allergens; Anti-acne agents such as isotretinoin, tretinoin, benzoyl peroxide; Anti-psoriasis agents, such as etretinate, cyclosporin, calcipotriol; Anti-itching agents such as capsaicin or nonivamide; Antiperspirant agents, such as methatropine nitrate, propantheline bromide, scopolamine, methscopolamine bromide, quaternary acyloxymethyl ammonium salts (GB 2010270 A); Physiologically active peptides and proteins, such as vasopressin or human growth hormone.

Dose levels for an active ingredient may range from 0.01 ng to 500 mg, especially 0.01 mg to 100 mg, for example 0.1 mg to 75 mg or 1 mg to 300 mg per application (spray application). c) optionally a physiologically acceptable organic polymer for film formation, such as acrylic acid, methacrylic acid and derivatives, polyacrylates and

Polyacrylate derivatives, such as polybutyl methacrylate and Polymethacrylic acid, polymethacrylate, ascorbyl palmitate, urethanes and urethane derivatives, carbomer, carnauba wax,

Cellulose derivatives, such as cellulose acetate phthalate, rosca mellose sodium, hydroxyethyl cellulose,

Hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hypromellose phthalate, crospovidone its derivatives,

Cetyl alcohol and its derivatives, microcystalline wax, poloxamer, polyethylene glycol, polyurethanes,

Polyvinyl acetates, polyvinyl acetate phthalate, polyvinyl alcohol, povidone, silicone gums and its derivatives,

Shellac, triglyceride derivatives.

Optionally, at least one plasticizer is included to establish the required elasticity. Examples include: polybutyl phthalate, benzyl benzoate,

Dibutyl sebacate, dimethyl phthalate, dibutyl phthalate,

Triacetin, glycol and its derivatives, benzyl benzoate,

Glycerine, mineral oil, lanolin, alcohols (e.g., C8 alcohols), petroleum, lanolin alcohols, polyethylene glycol, sorbitol, triacetin, triethylene citrates, propylene glycol,

Chlorobutanol, castor oil and gelatin. d) optionally at least one galenic excipient or a mixture of such galenic adjuvants,

 Diluent etc. according to the dosage form and / or release rates. The amount and nature of the auxiliaries should of course be compatible with the component c) used, such as cosolvents, surfactants,

Emulsifiers, antioxidants, preservatives,

Stabilizer. Examples of galenic adjuvants are Paraffin oils, isopropyl esters, myristates, ethanol,

Silicone oils and vegetable oils. Suitable surfactants are ethoxylated fatty acids, glycerol monostearate,

Phosphate esters and other customary emulsifiers and surfactants. An example of a preservative is hydroxybenzoate ester. Typical cosolvents and adjuvants are ethanol, propanol, isopropanol, acetone,

Dimethyl ether, glycol ethers, as

 Diethylene glycol monoethyl ether. These adjuvants must of course be compatible with the requirement that the aerosol composition after application

touched dry film forms. e) optionally at least one hautkosmetisch acting

Additive.

The components are for example in the following

Amounts in the aerosol composition contain: 30 to 90 wt .-% of component a), 0.000001 to 1 wt .-% of component b), 1 to 50 wt .-% of component c) (without plasticizer), 0, 1 to 20% by weight of plasticizer, 0 to 90% by weight of component d) and 0 to 90% by weight of component e), the sum of the components always being 100% by weight. The invention further relates to a use of such an aerosol dispenser for the application of a

transdermal agent to the skin, optionally pressurizing the vessel, wherein the dispenser is placed with the Aufsetzlippe on the skin, so that the Aufsetzlippe completely rests on the skin, and wherein the dispensing valve is actuated. The aerosol dispenser according to the invention can also be used for dermal application, ie the application of

Active ingredients that are topical or cosmetic

Applications are used.

In the following the invention will be explained in more detail with reference to figures showing only one embodiment. Show it:

FIG. 1 shows a cross-sectional drawing of a first variant of an aerosol dispenser according to the invention,

Figure 2: a cross-sectional drawing of a second

 Variant of an inventive

 Aerosol dispensers,

Figure 3: cross-sectional views of various

 Variants of a placement hood used in the invention, and

Figure 4: views of two variants of a Aufsetzhaube overlooking the Aufsetzlippe. FIG. 1 shows an aerosol dispenser 1 for

Application of a transdermal active pharmaceutical composition 2. One first recognizes a vessel 3 with the liquid active ingredient composition 2, which contains the pharmaceutical active substance. In the embodiment of Figure 1, the interior 4 of the vessel 3 is pressurized by means of a propellant gas. Alternatively to this may be provided a separate pumping device, not shown, which sets the interior 4 of the vessel 3 under increased pressure. The typical pressure is in each case about 1.1 bar to, for example, 5 bar (absolute). It can further be seen a sputtering device 6, which is capable of the liquid

 Active compound 2 in an aerosol or a

To convert spray mist. This atomizing device 6 is connected to the interior 4 of the vessel 3 via a

operable dispensing valve 7 connected. The dispensing valve 7 has for this purpose a handle 14. Furthermore, it can be seen that a Aufsetzhaube 9 is set up, which is placed with its container opening on the Behälter3. In the exemplary embodiment holds the container opening 10 on the container by adhesion. Alternatively they are

of course also form-locking connections,

in particular latching connections, detachable or non-detachable, between the container opening 10 and the container 3

used. The attachment hood 9 has an application opening 11 at the opposite end of the container opening 10. For this purpose, a Aufsetzlippe 12 is set up in the region of the application opening 11, which comes on the skin during application of the aerosol dispenser 1 for placement. In the illustrated embodiment, the attachment hood 9 is formed of a polyolefin material, while the

Aufsetzlippe 12 is formed and attached from a silicone material. Alternatively, the attachment hood 9 can of course also be formed from a uniform material, for example a thermoplastic elastomer, as explained in the general part of the description. In the illustrated embodiment, the attachment hood 9 relatively hard and dimensionally stable, while the Aufsetzlippe 12 is comparatively very soft and rubber-elastic design. It can be further seen that the cross-sectional area of the Aufsetzlippe 12 (perpendicular to the paper plane) is greater than the cross-sectional area of the container opening 10 (perpendicular to the paper plane) is formed. The Aufsetzhaube 9 has a substantially conically shaped lateral surface, in the embodiment in the sectional plane of

Paper surface with convex cone surface. Finally, it can be seen that the outlet opening 13 of the

 Atomizing device 6 in the direction of Aufsetzlippe 12 points. The ejected from the atomizing device 6 spray cone is optimally in the plane of the

Aufsetzlippe 12 formed with a diameter which is slightly larger than the diameter of the Aufsetzhaube 9 in the region of the Aufsetzlippe 12. In this way, only a small portion of the active ingredient composition impinges on an inner wall of the attachment hood 9, while the overwhelming proportion of the active ingredient composition is deposited in a defined manner on the area of the skin encompassed by the placement lip 12. In the exemplary embodiment, the cross sections of the container opening 10 and the

Application opening 11, viewed perpendicular to

Paper plane, parallel to each other. Alternatively, however, the cross sections can also be angled against each other

be aligned, so that in the core of the attachment hood also an elbow in the container opening 10th

having . FIG. 2 shows an alternative embodiment of an aerosol dispenser 1 according to the invention. To the First is the Aufsetzlippe 12 formed in material unit with the attachment hood 9 here. In a comparative examination of Figures 1 and 2 it can be seen that in the subject of Figure 2, the dispensing valve 7 by a

Pumping device 5a is replaced. With each stroke of the handle 14, this pumping device 5 a removes a defined quantity of the active ingredient composition 2 from the unpressurized interior 4 of the container 3 and guides it

Atomizing device 6 under pressure too.

FIG. 3 shows various possible cross-sectional shapes of an attachment hood 9. In FIG

shown conical cross-sectional shape. In the figure 3b can be seen a concave deformed conical surface. In Fibur 3c, the attachment hood is essentially

bell-shaped.

In Figure 4 are two of many possible

Querschittsformen in the field of Aufsetzlippe 12th

shown. Figure 4a shows a substantially

circular or annular Aufsetz lip 12, while the Aufsetzlippe 12 in the figure 4b in

Is formed substantially oval. In both cases, it can be seen that the application opening 11 is significantly larger than the container opening 10.

Claims

Claims:

Aerosol dispenser (1) for administering transdermal active pharmaceutical compositions, comprising a vessel (3) containing the active pharmaceutical ingredient in a liquid active substance composition (2), the interior (4) of which is provided by means of a

 Propellant gas is under pressure or the interior (4) by means of a pumping device (5) can be placed under pressure, or from which by means of a pumping device (5a) solution (2) can be removed, with one with the interior (4) of the vessel

 (3) associated atomizing device (6), with a between the interior (4) of the vessel (3) and the atomizing device (6) arranged actuatable dispensing valve (7) or pumping device (5a), characterized in that a Aufsetzhaube (9) set is, which has a container opening (10) which on the

Container (3) can be placed and that the attachment hood (9) has an application opening (11) with a Aufsetzlippe (12) for placing the Aufsetzhaube (9) on the skin. Aerosol dispenser (1) according to claim 1, characterized

characterized in that the Aufsetzlippe (12) and / or the Aufsetzhaube (9) made of a rubber-elastic

Material is formed.

Aerosol dispenser (1) according to claim 1 or 2, characterized in that the Aufsetzhaube (9) in the region of the Aufsetzlippe (12) has a circular or oval ring shape in cross section.

Aerosol dispenser (1) according to one of claims 1 to 3, characterized in that the cross-sectional area of the Aufsetzlippe (12) is greater than that

Cross-sectional area of the container opening (10).

An aerosol dispenser (1) according to any one of claims 1 to 4, characterized in that the Aufsetzhaube (9) is formed with a substantially conical lateral surface, with a straight, convex or concave in cross-section in the plane of the central axis of the cone

Conical surface.

Aerosol dispenser (1) according to one of claims 1 to 5, characterized in that the Aufsetzhaube (9) in the region of the Aufsetzlippe (12) has a lower hardness as in the area outside the Aufsetzlippe (12).

7. aerosol dispenser (1) according to one of claims 1 to 6, characterized in that the Aufsetzhaube (9) fixed or reversible with the vessel (3) is connectable.

Aerosol dispenser (1) according to one of claims 1 to 7, characterized in that the

 Atomizing device (6) has an outlet opening (13) which faces in the direction of the Aufsetzlippe (12).

Aerosol dispenser (1) according to one of claims 1 to 8, characterized in that the cross-sections of the container opening (10) and the application opening (11) are aligned parallel to each other or angled against each other.

10. aerosol dispenser (1) according to one of claims 1 to 9, characterized in that the

 Contains active substance composition (2) in the vessel (3), in particular consists of: a) a physiologically compatible organic or aqueous solvent,

b) a pharmaceutical agent, c) optionally a physiologically acceptable

organic polymer,

d) optionally at least one galenic adjuvant, e) optionally at least one skin-cosmetically active additive.

Aerosol dispenser (1) according to claim 10, characterized

in that the active substance mentioned under b) is a dermal or transdermal active substance.

Use of an aerosol dispenser (1) according to any one of claims 1 to 10 for applying an active substance to the skin, wherein optionally the vessel (3) is pressurized, wherein the aerosol dispenser (1) is placed with the Aufsetzlippe (12) on the skin in that the abutment lip (12) rests completely on the skin, and wherein the dispensing valve (7) is actuated

Use of an aerosol dispenser (1) according to claim 12, characterized in that the active ingredient

transdermal or dermal effect.

Use of an aerosol dispenser (1) according to one of claims 1 to 10 for the production of a

Aerosol dispenser (1) for applying an active substance 'to the skin of a human or animal Placing the Aufsetzlippe (12) on the skin and

Actuation of the dispensing valve (7).

Use of an aerosol dispenser (1) according to claim 14, characterized in that the active ingredient

having transdermal or dermal activity.