A system for opening a medical blister package

ES 2 525 262 T3

DESCRIPTION

Opening system of a medical blister

The present invention relates to a medical blister opening system.

Background of the invention

The psychological demands vary from person to person and even within the same individual in the course of life. Likewise, various disorders can affect psychological conditioning. For example, pregnant, lactating, and menopausal women may have increased needs for certain therapeutic nutrients, agents, or treatments, and reduced needs, or even tolerance, for other therapeutic nutrients, agents, or treatments. Satisfaction of the specific physiological conditioning of humans and other animals may require the use of a complex daily therapeutic regimen that requires the administration of various biologically active substances at different times of the day.

A WHO study estimates that only 50% of chronic disease patients in developed countries follow treatment recommendations. This can affect the health of the patient, and affect society in general when it causes complications due to chronic diseases, the formation of resistant infections or untreated psychiatric illnesses.

There is a wide spectrum of factors that play a role in poor patient compliance, including complexity of the regimen, unclear administration instructions, unclear treatment purpose, forgetfulness, and physical difficulty in compliance, for example. For example, in the opening of medicine containers.

This compliance problem is further compounded when the treatment regimen is complex, requires multiple doses per day or a period of treatment, or requires different doses of a combination of drugs. Avoidance of rigorous medication schedules can lead to decreased efficacy of therapeutic treatment. Conversely, careless administration of medications can increase the severity of undesirable side effects and exposure to unwanted safety risks, including death. Disposable pharmaceutical containers for administering drugs that are used to help patients improve their adaptation to medical treatment have been disclosed previously.

In order to help patients improve compliance and make them a follow-up patient, a common approach uses embossed or printed markings on the blister.

US 2007015728 provides a dosage container for the co-administration of a first and a second component of a therapeutic agent. The dosing container includes a first plurality of chambers without fluid communication, each chamber containing an individual dose of the first component and a second plurality of chambers, each chamber being able to reversibly receive at least one dose of the second component.

US 6,375,956 relates to a disposable administration apparatus that provides optimal therapeutic support for humans and animals by conveniently delivering a complex dosage regimen that requires the simultaneous administration of incompatible components in storage or of unequal dosing in a stable format in easy-to-use storage.

Document WO04089274 refers to a drug container, or kit, or presentation that facilitates the self-administration of drugs by patients, characterized by comprising one or more blister cards that incorporate instructions to the patient in printed form regarding the dosage of each unit, the type or nature of the active ingredient, the period of the day in which it should be taken and the treatment period, among other information.

Document US 2004266745 discloses a blister for a preparation useful in hormone replacement therapy, on which a system that facilitates the alternative administration of the daily dosage unit, preferably a scheme that uses integers from 1 to 28 to record the sequence of the specific dosage unit to be administered each day.

US 2007015839 discloses a daily drug delivery regimen for treating metabolic syndromes in one single pack. The packaging includes the doses to be taken at two different times of the day. The packaging may include the single day regimen or may include the multiple day regimen.

Other approaches have been reported to help patients improve their adherence to medical treatment.

Document US 4,627,432 relates to a device for administering drugs to patients comprising

ES 2 525 262 T3 a cylindrical chamber including a support to support a blister. The blisters are located in holes within the holder. A plunger is arranged to enter the chamber and open the blister supplied with it. When the blister is opened, the medicine can be withdrawn by a patient.

US 4,850,489 relates to dispensing packages containing chambers with at least two solid, non-mechanically connected dosage units. When necessary, the two contained pharmaceutical substances can be released at delayed intervals.

U2001030140A discloses a blister for a pharmaceutical treatment having a plurality of individual blisters suitable for containing a premeasured dosage of a pharmaceutical composition in the form of tablets, pills and capsules. In accordance with a predetermined schedule of administration, the sealed blisters can be opened by a tear, peel or push procedure.

US 4,889,238 relates to a drug container to improve compliance with a therapeutic regimen. The therapeutic regimen indicates a plurality of medications administered to a patient in a prescribed sequence and according to specific intervals. The package includes a multiplicity of blister cards that incorporate the medications in sequential order on the individual cards and from card to card. The blister cards are arranged in a stacked formation with their main dimensions generally oriented horizontally and arranged in order of use with the first to be used at the top. Also included is a base which houses the stack of blister cards and which is adapted to support the stack vertically and which provides lateral support to the edges of the blister cards. The base allows direct and unobstructed access to the uppermost blister card and only limited access to the edges of the blister cards. A cover is adapted to cover the base and can be moved to an open position allowing access to the uppermost blister card. Each blister card generally contains markings that indicate the order and sequence in which the contents of a particular blister recess should be consumed.

Document WO9822072A describes a pharmaceutical packaging to aid or increase patient compliance for the administration of a specific pharmaceutical substance regimen, comprising: a) at least one blister card divided into sections that separate each dose of the complex drug regimen ; each dose comprising marks indicating the time in which the dose should be administered; b) a patient information booklet comprising dosage information; c) a daily calendar comprising dosing information; and d) a reminder help.

US 4,254,871 relates to a packaging element for assembling blister strips containing a batch of drugs for a patient. The element comprises a collapsible sheet divided into a support member and a reinforcing member, the element characterized by a plurality of openings for receiving blister strips. The slide is marked to show the day of administration of the contents of each strip to improve patient compliance.

WO 03079959 relates to a tablet box for receiving and extracting tablets in a controlled manner. A commercially available blister can be located directly in the tablet carton, which is provided with an alarm device for removal of the tablets.

US 2002162769 discloses a prepackaged therapeutic regimen that includes two dosage units. Markings are included on the pharmaceutical dispensing container to distinguish between the first and second dosage units, administration instructions that teach the coordinated use of the dosage units.

Document EP 1502568 refers to an assembly for dispensing pharmaceutical products comprising perforated plates within a housing, combined with an electronic box, in which a blister is located within the assembly, which is on contacts to close a circuit and a Perforated oscillating sheet acts as a cover and blocks the blister packs selectively, it's new An acoustic and visual alarm is activated at the same time each day, according to the instructions incorporated by the blister to remind the patient to follow the regimen.

Document WO 2004/031050 relates to an improved blister having a tray comprising recesses to house, for example, tablets or capsules. The package is characterized by a manually removable foil partially attached to the top layer of the tray. The unfixed part comprises a tab having a graduated width for easy grasping and detachment of the sheet by the patient.

The pharmaceutical containers, dispensers, and containers discussed above are deficient in several respects. Significantly, none of the references set out presents a convenient, simple and effective way to facilitate the selective access and therefore the administration of substances, in particular when said substances are taken as part of a complex time-dependent sequential therapeutic regimen. Also, none of the above references specifically addresses a way to facilitate the simultaneous administration of prescription and non-prescription substances as part of a complex regimen. Likewise, none of the references

ES 2 525 262 T3 above addresses the problem of optimizing a pharmaceutical packaging or helps to improve patient follow-up for medical treatment. Thus, there remains a need for a simple, inexpensive and convenient means of providing optimal therapeutic support for humans and other animals and, in particular, for providing optimal support for humans and other animals with special therapeutic needs.

Furthermore, none of the above techniques solves the problem of compliance with packaging security. None of the above techniques provide a solution to the problem of inadvertently misusing a medicine, for example patients being able to access and therefore take drugs in the wrong sequential order.

Thus, there is a need for a simple and effective system that increases safety and compliance efficacy by imposing prescribed doses at prescribed intervals for drugs within a therapeutic regimen.

Object of the invention

It is an object of the present invention to provide a system that helps patients improve adherence to a medication regimen. It is a further object of the invention to provide a system that helps patients improve safety and efficacy in complying with a medication regimen.

It is a further object of the present invention to provide an alternative to the prior art.

In particular, it can be appreciated as an objective of the present invention to provide a system that solves the problems of the prior art mentioned above by allowing selective access to the blister after a preferred opening sequence.

Summary of the invention

The present inventive subject matter relates to a stable storage disposable dispensing system and an apparatus that provides optimal therapeutic support while overcoming the deficiencies of currently available pharmaceutical packages in a cost-effective, convenient, efficient and simple manner.

Thus, the above-described objective and other different objectives are intended to be obtained in a first aspect of the invention by providing a system for opening a container comprising a support sheet with at least two separate depressions adapted to house pharmaceutical compositions and to the least two overlapping cover sheets each covering at least one depression, comprising elements characterized in that access to one elements is obtained by removing the preceding superimposed cover sheet and in that access to other elements is obtained by sequentially removing the respectively preceding superimposed cover sheets.

The system allows the opening of containers formed by a support sheet that includes at least two depressions covered by separate cover sheets. These cover sheets overlap in predetermined areas that delimit elements that can be grasped and peeled or torn, pulling up and back to provide access to the relative depression located on the support sheet below. Removal of the first cover sheet by peeling or tearing the cover sheet or a gripper connected to it, provides access to the first depression and a second element which, in turn, can be peeled or torn to provide access to the second depression and its content and to the second element, and so on. The removal of the cover sheets can be obtained in a predetermined and specific sequential manner by superimposing the cover sheet that delimits the elements. This has the advantage of allowing access to the content of the relative depressions in a desired and predetermined sequence.

Sequential is defined as occurring in regular succession, while preceding is defined as prior following a specific spatial order, eg, the upper cover sheet precedes the immediate lower overlap. Therefore, access to the first element is obtained by removing the first cover sheet by a certain action, for example pulling or tearing, the cover sheet or a gripping element connected to it and access to the second element. it is obtained by removing the second cover sheet by means of a certain action, for example, pulling or tearing the first element, and so on.

The element at least partially delimited by the overlapping of the cover sheets can take the form of a tongue, a strip, a cutout, a notch or a flap. The element has the characteristics of being at least partially unsealed or not being tightly sealed on the support sheet. It has the function of providing a better grip to the user to peel or tear the cover sheet and gain access to the depressions. The shape, size, and configuration of the element are tied to its function. The element can have any shape and size that allows it to be gripped by a person or mechanically. The configuration of the

ES 2 525 262 T3 element can be any geometric shape or combination of shapes, for example triangular, circular or square. In some embodiments, the elements may have a user-friendly configuration, for example resembling a pad to provide better support for the user after use.

In some embodiments, the element can be made of a non-slippery material, such as rubber, or it can have a certain degree of surface roughness to provide a better grip.

The elements can be placed at different locations along the edges of the cover sheets.

In some embodiments, the element is a flap that may have a projection to allow a better grip. The projections can be embossed or printed. The projections can also incorporate information printed on the flap element.

In some embodiments, the package may be a blister in which the depressions take the shape of blisters. In some other embodiments, the package may be a medical blister in which the depressions in the backsheet contain a pharmaceutical composition.

The above-described objective and the other objectives are intended to be obtained in a second aspect of the invention by providing a blister that comprises a support sheet with at least two separate depressions adapted to house pharmaceutical compositions and at least two cover sheets covering each one at least one depression, wherein the at least two cover sheets are at least partially sealed on the support sheet around at least two depressions, and the at least two cover sheets overlap and delimit at least two elements characterized in that access to an element is obtained by removing the preceding superimposed cover sheet and because access to the additional elements is obtained by sequential removal. of the respectively preceding superimposed cover sheets.

The blister, for example a medical blister, comprises a support sheet with depressions and is characterized in that access to the element that allows admission to the next depression is hindered by the anterior element, so that access to the posterior depression is only possible allows after access to the previous depression has been achieved. Administration of the individual pharmaceutical composition is therefore only allowed following a predetermined sequential manner.

The backing sheet of the present blister can be made embossed, deep drawn by molding, or vacuum formed from plastic, plastic laminates, plastic / paper laminates, or plastic / metal or metal sheet laminates. Exemplary non-limiting suitable plastics for the backing sheets are films and film laminates containing PVC, polyamides, polyolefins, polyesters, polycarbonates, and combinations thereof. The backing sheets may also incorporate a gas, vapor and light barrier layer. Said barrier layers can be a metal foil, such as an aluminum foil embedded in a plastic laminate or useful ceramic material layers or metallic layers embedded between two layers. Ceramic layers can be produced by evaporation of metals, oxides or nitrides of aluminum, silicon and other metals and semimetals under vacuum and deposit of the substances on a plastic substrate. The procedures are known as chemical vapor deposition and physical vapor deposition or sputtering. The ceramic layers can preferably contain aluminum oxides or silicon oxides or they can be mixtures of various oxides, if desired they can also be mixed with metals, such as silicon or aluminum. Metallic layers can be created by evaporating metals in a vacuum and depositing the metals on a plastic substrate; aluminum layers can be mentioned here by way of example. The plastic substrate can be a plastic film or a plastic base made from the plastics mentioned above.

The cover sheet material can be a metallic foil, such as an aluminum foil or a laminate containing an aluminum foil. The aluminum foil can be replaced with a plastic foil, plastic laminates, plastic / paper laminates, or plastic / metal foil laminates. The aluminum foil can also be replaced with a plastic that exhibits low elasticity and poor stretching properties. A plastic material that exhibits these properties can be obtained when large amounts of fillers are added to the plastic.

Filler is defined herein as particles of a material that are added to the plastic material to provide properties that are different from those of the plastic alone.

In some embodiments, the cover sheet may comprise at least two thin sheets, for example a first thin sheet, such as an aluminum thin sheet or a laminate containing an aluminum thin sheet, and a second thin sheet such as an adhesive tape. The adhesive tape has the function of removing at least part of the first thin sheet located below to provide access to the corresponding depression after the desired sequential opening. The superposition of the various adhesive tapes can produce the desired sequential opening on a first individual thin sheet. For example, all depressions may be covered by a single first thin sheet, such as a sheet

ES 2 525 262 T3 thin aluminum. A series of separate adhesive tapes overlapping in predetermined areas can act as cover sheets as described above. Separate adhesive tapes can be overlapped to delimit elements that can be grasped, peeled off or torn by pulling up or back causing the removal of the first thin sheet, for example aluminum thin sheet, which covers the access to the relative depressions located below backing sheet. Removal of the first adhesive tape by peeling or tearing the adhesive tape or by a gripping element connected to it causes the removal of the area of ​​the first thin sheet located on the first depression, in effect providing access to the first depression. In this way, a second element that, in turn, can be detached or torn, causing the adhesive tape to be removed from the area of ​​the first thin sheet located on the second depression; in effect providing access to the second depression and the content and the second element and so on. In general, sequential opening can be obtained by removing the adhesive tape in a specific predetermined and sequential manner determined by the overlapping of the adhesive tapes.

The backing sheet typically incorporates a plurality of cup- or plate-shaped depressions without limitation.

In some other embodiments, the depressions in the backing sheet can be obtained by calendering, molding, injection molding, or other known thermoplastic processes. The depressions may be surrounded by ridges, said ridges together forming an interconnected flat plane. The support sheets are prepared, for example, as an endless strip with the contents within the recesses and grouped with the cover sheet material, in particular in the form of a thin sheet, also in the form of an endless strip. The cover sheets cover the backing sheet completely and, for example, by sealing or adhesive bonding they are attached to the backing sheet at the shoulders. The cover sheets can be sealed or adhesively bonded to the shoulders over the entire area or, by choosing a special sealing tool or bonding pattern for the purpose, this sealing or bonding may be only partial. For example, the endless strip of a backing sheet sealed with covered sheets can be cut to the desired size. This can be done, for example, using a stamping tool. At the same time, the blister can have outer contours, or it is possible to provide weaknesses in the cover sheet or the support sheet in order to allow the blister to bend or create cover segments, allowing easy removal. of the cover sheets and the removal of the contents.

Daymarks may also be incorporated into the blister of the present invention. The brands of the day can be of various types, without limitation. The day marks correspond to at least two distinct depressions in the support sheet. For example, without limitation, the day stamps can be for a specific day of the week, for example, Monday, Tuesday, Wednesday, Thursday, Friday, Saturday, Sunday, or an abbreviation of that day, a specific date, or a general sequence. of days, such as day 1, day 2, day 3, and the like. The day markings can be indicated directly on the pharmaceutical composition or elsewhere on the blister.

Time stamps can also be incorporated into the blister of the present invention. Timestamps can be of any type, without limitation. Timestamps correspond to at least two distinct time periods, but can correspond to any plurality of different time periods without limitation. For example, without limitation, timestamps can indicate a general time of day or a specific time of day. Exemplary non-limiting general times of day may be any of the following: AM, PM, morning, early afternoon, afternoon, day, night, day time, night time, and combinations thereof. Each row or separate column of the present blister can each indicate a time of day, such as indicating AM dose and PM dose of a drug. A predetermined area provided on a blister can be color-coded for time stamps. The blister can also include a key that defines or explains the color code. For example, without limitation, the area around the depression containing the pharmaceutical composition to be taken in the morning could be orange, while the areas containing the depression containing the pharmaceutical composition to be taken first thing in the morning. late could be blue. Likewise, the depression contained in the pharmaceutical composition can be directly color-coded. For example, each depression containing the pharmaceutical composition to be administered in the morning could be identified by the yellow color and the composition containing the pharmaceutical composition to be administered in the evening could be identified by the red color, without limitation. Also, each individual pharmaceutical composition could be individually color coded for timestamps. Each depression can be manufactured from a transparent or translucent material so that the color code on the pharmaceutical composition can be visible while the pharmaceutical composition is within the depression. For example, each depression containing AM doses could have a green border and be clearly visible while inside the blister. Alternatively the depression could be a dull color shade. The color key can be provided on the blister to indicate which color corresponds to each date or time for compounding. The markings provide a reliable and effective feedback system because the patient can determine whether the appropriate dosages have been taken on the correct days at the correct times by comparing the markings on the container with a calendar or clock.

The invention is particularly, but not exclusively, advantageous in providing assurance of patient compliance. Since access to depressions contained in pharmaceutical compositions only

ES 2 525 262 T3 is possible by following a predetermined sequential order, inadvertent wrong taking of a drug due to patient errors is minimized. For example, patients with vision problems, for example people with severe visual impairments, may not always be able to identify the markings present on the packaging and therefore unintentionally take the medicine in the wrong order. With the blister according to the invention, only a predetermined and desired sequence of opening is possible and thus a certainty in compliance is achieved. Pharmaceutical compositions that can take advantage of the invention can also be contraceptives or drugs for chronic diseases that often require sequential tablet-taking for optimal efficacy. The invention can provide security in compliance since with the package according to an embodiment of the invention, erroneous sequential picking due to erroneous sequential opening cannot be achieved.

A pharmaceutical composition can comprise any biologically active substance, without limitation. Preferably, the dosage units of the present invention comprise vitamin A, B vitamins, vitamin C, vitamin D, vitamin E, vitamin K, essential fatty acids, folic acid, iron, calcium, magnesium, potassium, copper, chromium, zinc, molybdenum, iodine, boron, selenium, manganese, derivatives thereof or combinations thereof. Exemplary non-limiting biologically active substances of the present inventive subject matter may include thiamine, thiamine pyrophosphate, riboflavin, flavin mononucleotide, flavin adenine dinucleotide, niacin, nicotinic acid, nicotinamide, niacinamide, nicotinamide dinucleotide, biotinamide and adenine, and tryptophan. , pantothenic acid, ascorbic acid, retinol, retinal, retinoic acid, beta-carotene, 1,25-dihydroxycholecalciferol, 7-dehydrocholesterol, alpha-tocopherol, tocopherol, tocotrienol, menadione, menaquinone, phylloquinone, naphthoquinone, calcium, calcium carbonate, calcium sulfate, calcium oxide, calcium hydroxide, calcium apatite, calcium malate citrate, calcium gluconate, calcium lactate, calcium phosphate, levulinate calcium, phosphorus, potassium, sulfur, sodium, docusate sodium, chloride, magnesium, magnesium stearate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium sulfate, copper, iodine, zinc, chromium, molybdenum, carbonyl iron, ferrous fumarate, polysaccharide iron, and combinations and derivatives thereof, without limitation. Exemplary non-limiting derivatives of vitamin compounds include salts, alkali salts, esters, and chelates of any vitamin compound.

The pharmaceutical composition may be prescription or non-prescription substances or excipients for use in prescription or non-prescription substances. Exemplary non-limiting prescription substances include 13C-urea (Helicobacter test), 15-Methyl-prostaglandin F2a, 1a-Hydroxyvitamin D3, 2,4-dichlorobenzyl alcohol, 5-aminolevulinic acid hydrochloride, 5-aminolevulinic acid (5-ALA), abacavir, abacavir / lamivudine, abacavir / lamivudine / cidovudine, abatacept, abciximab, acamprosat, acarbose, acebutolol, acepromazine, acetaminophen, acetate, acetazolamide, acetophenazine, acetylcysteine, acycloxyclovir, acetylsalicylic acid acitretin, acrivastine, acyclovir, adalimumab, adapalene, adefovir dipivoxil, adenosine, adrenaline, aesculin, agalsidase alfa, agalsidase beta, agalsidase-alfa, agalsidase-beta, agomelatín, agomelatina, alanina, albuminina (human), alemdestucinab, alemdestucinab alendronate sodium / cholecalciferol, alendronic acid / cholecalciferol, alfacalcidol, alfentanil, alfuzosin, alginic acid, alglucosidase alfa, alimemazin, aliskiren, aliskiren hemifumarate / hydrochlorothiazide, Alitretinoin, Allopurinol, Almitrine, Almotriptan, Alprazolam, Alprenolol, Alprostadil, Alteplase, Aluminum Aminoacetate, Aluminum Hydroxide, Aluminum Sucrose Sulfate, Alkalic, Amantadine, Ambenon, Ambrisentan, Ambroxol, Amfeprammon, Amyllidotride Aminogluide, Amine Aminogluoride , amiodaron, amisulpride, amitriptyline, amlodipine, amlodipine besylate / valsartan / hydrochlorothiazide, amlodipine / valsartan besylate, amlodipine / valsartan, amorolfine, amoxicillin, Amphotericin B, ampicillin, amprenavir, amsacrine, amylase, amylmetacresol, anagrelide, anakinra, anastrozole, anidulafungin, antazolin, antithrombin, antithrombin alfa, anti-thymocytoglobulin, apomorphine, apraclonidine, aphroxin, arginiprazine, arginiprazine, arginiprazine, arginiprazine, arsenic, articaine, ascorbic acid, asparagine, atazanavir, atenolol, atomoxetine, atorvastatin, atosiban, atovaquone, atropine, auranofin, aurothiomalate, aviptadil, azacitidine, azacitidine, azapropazone, azathioprine, azelaic acid, azelastine, azetazolamide, azithromycin, aztreonam, human C1-esterase inhibitor aztreonam, bacampicillin, Bacillus Calmette Guérin (Danish lineage 1331), Bacillus Calmette Rérpette Guérin P273, derivative P2-RIVM 1173, derivative Calmette la Guérin P273 baclofen, balsalazide, bambuterol, barium sulfate, basiliximab, bazedoxifene, becaplermin, beclomethasone, beclomethasone dipropionate, benazepril, bendroflumethiazide, bensatropine, benserazid, bensylpenicillin, benzalkonium chloride, benzenecarboxylic acid, benzenemethanol, benzocaine, benzoic acid, benzoyl peroxide, benzydamine, benzylpenicillin, beta-carotene, betahistine, betaine, betaine anhydrous, betamethasone, betamethasone-17valerate, betamethasone-21-phosphate-acetate, betamethasone-21-acetone , betaxolol, bevacizumab, bexarotene, bicalutamide, bimatoprost, bimatoprost / timolol, biotin, biperiden, bisacodyl, bisoprololfumarate, bivalirrudin, black rubber blend (PPD blend), bleomycin, borax, bortezomib, bosentan, botulinum toxin type A, botulinum toxin type B, brimonidine, brimonidine tartrate, brinzolamide, brinzolamide / timolol, bromazepam, bromhexine, bromocriptine, butanedesomidephenide , bupivacaine, buprenorphine, buprenorphine / naloxone, bupropion, buserelin, buspiron, busulfan, butylscopolamine, cabergoline, iodinated cadexomer, caffeine, mixture of caines, calcipotriol, calcitirole, calcitonin, calcitonin (salmon), calcium, calcium acetate, calcium carbonate, calcium chloride, calcium fluoride, calcium folinate, calcium gluconate, calcium lactogluconate, calcium polystyrene sulfonate, canakinumab, candesartan-cilexetil, capecitabine, capprilicine, carbabetic mixture, capprilicin, carbabetic , carbidopa, carbimazole, carbomer, activated carbon, carboplatin, carboprost, carglumic acid, carmellose sodium, carmustine, carvedilol, caspofungin, catumaxomab, cephalexin, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, celecoxib, cefaclor, cefadroxil, cephalexin, cephalothin, cephradine, certolizumab pegol, cetirizine, cetrorelix, cetuximab, cinidine, clofibrate, clomethiazole, chlorophenolipheniazole, chloralipheniazole, chloralipheniazine , chlorhexidine,

ES 2 525 262 T3 chloride, chloriongonadotropin, chloroquine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, clotrimazole, cholecalciferol, vitamin D3, choline theophyllinate, choriogonadotropin alfa, choriongonadotropin (hG), human choriongonadotropin (hG), choriongonadotropin (hG) cyclopirox, cyclopyroxolamine, cyclosporine, cidofovir, cilastatin, cimetidine, cinacalcet, cincocaine, kinetazon, cinnamaldehyde, cinnamyl alcohol, cinnarizine, ciprofloxacin, cis (Z) flupentixoldecanoate cisatracurium, cisplatin, citalopram, CI + Me-isothiazolinone (Kathon CG), cladribine, cladribine, clarithromycin, clavulanic acid, clemastine, clemastine, clindamycin, clioquinol, clobazam, clobetasol propionate, clobetason17-buttomyrate, chlobetason17-buttomyrate, chlobetason17-butomyrate clonazepam, clonidine, clopamide, clopidogrel, clotrimazole, cloxacillin, clozapine, cobalt (ll), copper, copper acetate, codeine, colesevelam, colestipol, cholestyramine, colistimethate sodium, corticotropin, cortisone, cyanocobalamin, cyanocobalamin, vitamin B12, cycllandelar, cyclizine, cyclopentolate, cyclophenyl, cyclophosphamide, cyproheptadine, cyproterone, cyproterone acetate, cysteamine, cysteine, cystine, cytarabine, dacarbybine, danumatrylate, dacarbumane, dapstethrilate , daptomycin, darbepoetin alfa, darifenacin, darifenacin, darunavir, dasatinib, daunorubicin, deferasirox, deferiprone, deferoxaminmesilate, degarelix, demeclocycline, depreotide, desflurane, desipramine, desirudin, deslanoside, desloratadine, desloratadine (as sulfate), desmopressin, desogestrel, deoxymethasone, dexamethasone, dexchlorpheniramine, dexibuprofen, dexketoprofen, dexpanthenol, dexpanthenol, dexamine 70, dextranomethasone, dexamine-40 dextropropoxyphene, diazepam, diazoxide, dibotermine alfa, diclofenamide, diclofenac, diclofenac sodium, dicloxacillin, diculmarol, didanosine, dienogest, digoxin, dihydralazine, dihydroergotamine, dihydrogesterone, dihydrotachysterol, dihydroxyaluminum, sodium carbonate, dipotassium chloracepate, diltiazem, dimeglyumingadopentetate, dimenhydrinate, dimethylaminodiphenylbutene, dimethicone, dimethicone, ferrofumarate, diphenolhydrogen, dinitrogen oxide, dipothenol dihydrogenate, dichlorohydronate disodium phosphate, disopyramide, disulfiram, dixirazine, dobutamine, docetaxel, docosahexaenoic acid (DHA), docusate, dofetilide, domperidone, donepezil, dopamine, doripenem, dornase alfa, dorzolamide, dosulepine, doxapram, doxazosin, doxepin, doxorubicin, doxorubicin hydrochloride, doxycyclin, doxycycline, droperidol, drospirenone, alfaxetreco, active duzolidine, ebastide, ebastide, ebastide, ebastide, active , eculizumab, efalizumab, efavirenz, efavirenz / emtricitabine / tenofovir disoproxil (as fumarate), eflornithine, eicosapentaenoic acid (EPA), econazole, eletriptan, emedastine, emepronium, emtricitabine, emtricitabine / tenofovir disoproxil, enalapril, enfuvirtide, enoxaparin, entacapone, entecavir, ephedrine, epinephrine, epirubicin, eplerenone, epoetin alfa, epoetin beta, epoetin delta, epoetin zeta, epoprostenol, epototermina epóxicata, resin epóxicata , eptifibatid, eptifibatide, eptotermin alfa, erdostein, ergocalciferol, vitamin D2, ergotamine, erlotinib, erlotinib, ertapenem, erythromycin, escitalopram, eslicarbazepine, eslicarbazepine acetate, esmolol, esomeprazole, estradiol, estradiol valerate, estradiol valerate, estramustine, estramustine phosphate, estriol, ethambutol, etanercept, etanercept, ethacrinazide, ethambutol, ethinyl estradiol, ethosuximide, ethylenediamine, ethylmorphronate, ethylenediamine, ethylmorrhophosphate, etoricoxib, etravirin, etravirine, ethulose, eugenol, everolimus, exemestane, exenatid, exenatide, ezetimibe, ezlocillin, factor IX, factor VIII, famciclovir, febuxostat, felodipine, felipressin, fenoterol, fentanyl, fentanyl citrate, ferric salts, ferritetrasemisodium, ferrous salts, ferrous succinate, ferumoxsil, fesoterodine, fexofenadine, fibrinogen, fibronectin, filgrastim, finasteride, fish oil (fiskeolia), fleconacainvoxate, fluconazole, fluconazole, fluconazole, fluconazole, flucytosine, fludarabine phosphate, fludrocortisone, fludrocortisone acetate, flumazenil, flumedroxone, flumethasone pivalate, flunarizine, flunitrazepam, fluocinolone acetonide, fluocinonide, fluocortolon 21-pivalate, fluoride, fluorometholone, fluorouracil, fluoxetine, fluoxymesterone, flupentizole, fluphenazine decanoate, fluphenazine, flurbiprofen, flutamide, fluticasone furoate, flvastatin propionate, foluticasone, fluparin, hephenol propionate, foluticasone, fluparin , follitropin beta, follitropin-a (rfSH), follitropin-β (rfSH), fomivirsen, fondaparinux, fondaparinux sodium, formaldehyde, formoterol, fosamprenavir, fosaprepitant dimeglumine, Sodium fosinopril, fosphenytoin, framycetin, frangula bark, frovatriptan, fulvestrant, furosemide, fusidic acid, gabapentin, gadobutrol, gadodiamide, gadofosveset, gadoteridol, gadoteric acid, gadoversetamide, galantamine, galsyclobulfase, ganixpina, ganixphenolphase , gemfibrozil, gentamicin, geraniol, gestiondene, glatiramer acetate, glibenclamide, gliclazide, glimepiride, glipizide, glucagon, glycopyrronium, glucosamine, glucose, glutamine, glutathione, glycerol, glycerophosphate, glyceryl nitrate, glyceryl nitrate, glyceryl trinitrate, glycine, glycopyrrone, glycyl-glutamine, glycyl-tyrosine, golimumab, goserelin, gramicidin, granisetron, grisectoridine, haloperidine, cofanfacine, grisectoridine, haloperidine heparin, heparinoid, hesperidin, hexaminolevulinate, histamine, histidine, histrelin, human coagulation factor IX, human fibrinogen / human thrombin, human normal immunoglobulin, Human normal immunoglobulin (IVIg), hydralazine, hydrochloride, hydrochloroquine, hydrocortisone acetate, hydrocortisone, hydrocortisone-17-butyrate, succinate, hydrocortisone, hydrogen peroxide, hydromorphone, hydroxychloroquine, hydroxyprogesterone, hydrocobaxycine, hydroxyprogesterone, vitamin B12, hydroxyprogesterone, hydrocobaxycarmine , hydroxycitronellal, hydroxyethylrutoside, hydroxyethyl starch, hydroxyurea, hyoscine, hyoscine butylbromide, hyoscyamine, hypromellose, Ibandronic acid, Ibandronic acid, ibritumomab tiuxethan, ibuprofen, icatibant, ichtamol, icodextrin, idarubicin, idursulfase, ifosfamide, iloprost, imatinib, imatinib mesylate, imiglucerase, human imipenem, imipramodramine, immunoglobulin (human immunoglobulin), immunoglobulin (human immunoglobulin) , indapamide, indinavir, indomethacin, infliximab, inositol nicotinate, insulin, insulin aspart, insulin aspart protamine, insulin detemir, insulin glargine, insulin glulisine, insulin human (rDNA), insulin lispro, insulin lispro protamine, human insulin, human isophane insulin, interferon alfa-2b, interferon alfacon-1, interferon beta-1a, interferon idoxuridine, interferon-alfa, interferon-alfa-2b, interferon-beta-1a, interferon- beta-1b, interferon-gamma-1b, interleukin-2, iobitridol, iodinine, iodixanol, ioflupane (123 I), iohexol, iomeprol, iopromide, iotrolan, ioversol, ipratropium, irbesartan, irbesartan / hydrochlorothiazide, isocaruineazolide , isoflurane, isoleucine, isoniazid, human isofaninsulin, isoprenaline, isosorbide dinitrate, isosorbide mononitrate, isotretinoin, isradipine, itraconazole, ivabradine, ketobemidone, ketobemidone,

ES 2 525 262 T3 ketokonazole, ketoprofen, ketorolac, ketotifen, kolofon, creatinine monohydrate, creatinine monohydrate, labetalol, lacidipine, lacosamide, lactate, lactic acid, bacteria-producing lactic acid, lactulose, lamivudine, lamivudine, lamidomivigine, lanolin, lanreotide, lansoprazole, lanthanum, lapatinib, laronidase, laropiprant, lasofoxifene, latanoprost, lecithin, leflunomide, lenalidomide, lenograstim, lepirudin, lercanidipine, letrozole, leucine, leucovorin, leuprorelin, levetiracetam, levocabastine, levocetirizine, levodopa, levofloxacin, levofolinic acid, levomepromazine, levonorgestrel, levothyroxine, lidocaine, lincomycin, linezolid, liothyronine, lipase, liraglutide, lisinopriline, lithium loperamide, lithium loepramide, lithium lepramide, loepramide, lithium carbonate, lepramide , lopinavir, loratadine, lorazepam, lormetazepam, lornoxicam, losartan, lovastatin, lutropin alfa, lymecycline, linestrenol, lipresin, lysine, macrogol 3350, magnesium, Magnesium carbonate, magnesium chloride, magnesium hydroxide, magnesium oxide, magnesium sulfate, malathion, mangafodipyr, mangano, mannitol, maprotiline, Maraviroc, mebendazole, mebeverine, mecasermine, mecillinam, meclozine, medroxyprogesterone, medroxyprogresterone acetate, medroxypropyl acetate mefruside, megesterol, megestrol acetate, melatonin, melphalan, meloxicam, melperon, melphalan, memantine, meningococcal polysaccharide, menotropin (hmG), mepensolar, mepivacaine, meprobamate, mepyramine, mercaptamine bitartrate, mercaptobenzothiazole, mixed mercapts, mercaptopurine, meropenem, mesalazine, mesna, mesterolone, mestranol, methacycline, methoxedrine, methenamine, metformin, methyldopa, methadone, methenamine, methionol ethylene glycine, methoxylengine, methenol methyl, methyldopa, methylergometrine, methylergotamine, methylnaltrexone, methylnaltrexone bromide, methylperon, methylphenidate, methylprednisolone, Methylprednisolone acetate, methylprednisolone succinate, methylprednisolone, methylcopolamine, methylprilon, methixen, metoclopramide, mettopimazine, metoprolol, metronidazole, methithlotiazide, mexiletine, mianserin, micafungin, miconazole, midartazorostide, micafungin, miconazole, midartazorostide, mitaxidifilin, misanthroxin, midartazolamide mivacuriuo, moclobemide, modafinil, molybdenum, mometasone furoate, moroctocog alfa, morphine, moxaverine, moxifloxacin, moxonidine, mupirocin, mycophenoic acid, mycophenolate mofetil, nabumetone, nadolol, nafarelin, nalbuphine, nalidixic acid, naloxone, naltrexone, nandrolone, naphazoline, naproxen, naratriptan, natalizumab, natamycin, nateglinide, nebivinomycin, neostena, nelarabin, nebivinomycin, neostena, nelarabine, nebivinomycin, neostena, nelarabine , nevirapine, niceritrol, nickel, nicomorphine, nicorandil, nicotine, nicotinamide, nicotinic acid, nicotinic acid / laropiprant, nicotinyl alcohol, nifedipine, nilotinib, nimodipine, nifedipine, nitisinone, nitrazepam, nitrendipine, nitric oxide, nitrofurantoin, nitrogen, nitrogen oxide, nitroprusside, nizatidine, nonacog alfa, noradrenaline, norelgestromin, norelgestromin / ethinyl estradiol, norethisterone acetate, norethisterone, norfloimistaxapine, norgestine, norgestin, oak, nostril, norgestine , octocog alfa, octreotide, ofloxacin, olanzapine, olmesartan medoxomil, olopatadine, olsalazine, omalizumab, omeprazole, ondansetron, opipramol, opium, Oral Cholera Vaccine, Orciprenaline, Orlistat, Ornidazole, Ornithine, Orphenadrine, Oseltamivir, Osteogenic Protein 1: BMp-7, oxaliplatin, oxazepa, oxazepam, oxcarbazepine, oxymetholone, oxyphenziclimine, oxytetracycline, oxprenolol, oxybutynin, oxycodone, oxygen, oxymetazoline, oxytetracycline, oxytocin, paclitaxelmine, pallyziferonum, paclitaxeldermine, pallyciferonum, paclidonyl albumin, pallidonytonmine, palyziferone, Panitumumab, Pantoprazole, Pantothenol, Vitamin B5, Pantothenic Acid, Papaverine, Paracetamol, Paraffin Oil, Parathyroid Hormone (rDNA), Parecoxib, Paricalcitol, Paroxetine, Pegaptanib, Pegilaptanib sodium, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pegylated interferon-alfa-2a, pegylated interferon-alfa-2b, pemetrexed, pencyclovir, penfluridol, penicillamine, pentaerythroxytoxivernobitaline, pentaerythroxytoxivernobitalin perflutron, pergolide, periciazine, perindopril, permethrin, perphenazine decanoate, perphenazine, pertussis toxoid, pethidine, pethidine, phenazone, phenazone salicylate, phenemal, fenfluramine, phenobarbital, Phenoperidine, phenoxymethylpenicillin, phenprocoumon, fentanyl, phentolamine, phenylamine, phenylbutazone, phenyleprine, phenylpropanolamine, phenytoin, phosphate, phosphestrol, phytomenadione, vitamin K1, phytominadione, pilocarpine, pimecrolimioglitazitazide, pimecrolimioindium, pimoolitazitazide, pimoolitazitazide, pimoolitazide, pimoolitazide, pimoolitazitazide, pimoolithoglitazide / metformin hydrochloride, pipamperone, piperacillin, pyritramide, piroxicam, pivampicillin, pivmecillin, pizitifen, pizotifen, plasminogen, plerixafor, podophyllotoxin, polidocanol, polyestradiol phosphate, polygelin, polymyxin B, polythiazide, posaconazole, potassium, potassium acetate, potassium chloride, potassium dihydrogen phosphate, potassium dichromate, potassium hydroxide, potassium phosphate, p-phenylenedolyamine, p-phenylenedolyamine, p-phenylenedolyamine pravastatin, prazosin, prednisolone, prednisolone sodium phosphate, pregabalin, prenalterol, prilocaine, primidone, probantelin, probenecid, procaine, procainamide, procarbazine, prochlorperazine, procilidine, proetazine, progesterone, proguanil, proline, promethazine, propafenone, propantheline bromide, propiomazine, propofol, propranolol, propylthiouracil, propiphenazone, proscillaridine, protamine, protein C, human protein C, protein S, protudopridatyline, proxucaetin as sulfate), pt-butylphenol-formadehyde-resin, pyrazinamide, pyridostigmine, pyridoxine, pyridoxine, vitamin B6, pyrityldione, pirvin, quetiapine, quinagolide, quinapril, quinine, quinoline mixture, rabeprazole, raffinose, raloxifene, raltegravir, ramipril, ranibizumab, ranitidine, ranolazine, rasagiline, rasburicase, reboxetine, recombinant human erythropoietin alfa, remifentanyl, repaglinide, reserpine, retinol, retinol, retinol, retinol, retinol, retinol, retinol, retinol, retinol, retinol, retinol, retinol, retinol ribavirin, riboflavin, vitamin B2, rifabutin, rifampin, riiterol, rilonacept, riluzole, rimexolone, rimonabant, risedronat, risperidone, ritonavir, rituximab, rivaroxaban, rivastigmine, rizatriptan, rocuronium, romiplostim, ropinirole, ropivacaine, rosiglitazone, rosiglitazone / glimepiride, rosiglitazone / metformin, rosuvastatin, rotavirus, rotigotine, roxithromycin, rufinamide, cascara extract, salicylic acid, salazosulfapyridium, salicylic acid, salazosulfapyridium, salicylic amine, salazosulfatameterpyrillic acid, salicylic acid [153sm] pentasodium lexidronam, sapropterin, saquinavir, saxagliptin, scopolamine, selegiline, selenium, selenium disulfide, senna glycosides, serine, sertindole, sertraline, sevelamer, sevelamer (carbonate), sibutramine, sildenafil, simethicone (activated dimethicone), simvastatin, sirolimus, sitagliptin, sitagliptin / metformin hydrochloride, sitagliptin phosphate monohydrate / ketaxenthamine hydrochloride, sitaxenthamine hydrochloride, sitaxenthamine hydrochloride , sodium oxybate, sodium phenylbutyrate, sodium cromoglycate, sodium aurothiomalate auranofin, sodium picosulfate, solifenacin, silver sulfadiazine, somatotropin, somatrem, somatropin, sorafenib, sorbitol, sotalol, spectinomycin, spiramycin, spironolactone, stanozolol, stavudine,

ES 2 525 262 T3 stiripentol, streptokinase, strontium ranelate, sucralfate, sufentanil, sugammadex, sulbentine, sulesomab, sulfamethizole, sulfamethoxazole, sulfasalazine, sulfate, sulfisomidine, sulfur hexafluoride, tagline, sulimpyride, sumatribiptan, sulpholitide, sumatriburide, tagline, sinuspiride , tafluprost, tamoxifen, tamsulosin, tasonermin, taurine, tazobactam, tegafur, teicoplanin, telbivudine, telithromycin, telmisartan, telmisartan / hydrochlorothiazide, temoporfin, Temozolomide, Temsirolimus, Tenecteplase, Teniposide, Tenofovir disoproxil, Tenoxicam, Terazosin, Terbinafine, Terbutaline, Teriparatide, Terlipressin, Terodiline, Testosterone, Testosterone Enanthate, Testosterone Undecanoate, Tetanic Toxoid, Tetracillinenazoline, Tetracylofenazine, Tetracylofenazide, Tetracidilinazine theophylline and ethylenediamine, thiamazole, thiamine, vitamin B1, thiethylperazine, thioguanine, thiomersal, thiopental, thioridazine, thiotepa, titixene, threonine, Human thrombin, thyrotropin alfa, tiagabine, thiamazole, thiamine, thiaprophenic acid, tibolone, tigecycline, tigecycline, timolol, tinidazole, tinzaparin, tiotropium, tipranavir, titanium dioxide, tizanidine, tobramycin, tocilizumab, vitamin E, tocopheryl, tocopheryl tolazamide, tolbutamide, tolcapone, tolfenamic acid, tolterodine, tolvaptan, topiramat, topotecan, toremifene, trabectedin, tramadol, trandolapril, tranexamic acid, trastuzumab, travoprost, travoprost, travoprost / timolol, treosulfan, treprostinil, triacelluvax, triamcinolone acetonide, triamcinolone hexacetonide, triazolam, trifluoperazine, triglyceride, trimetazidine, trimetaphan, trimethoprim, trimipramine, triptorelin, trophotrombine, chlorphotropyne, triptorelin, thrombidine, trophotropicide, triptorelin, thrombidine, trophotropicide, chloro, triptorelin, thrombide ulipristal, urofollitropin (uFSH), urokinase, ustekinumab, valacyclovir, valdecoxib, valganciclovir, valine, valproate, valsartan, vancomycin, vardenafil, varenicline, varenicline tartrate, vasopressin, venlafaxine, verapamil, verteporfin, vigabatrin, vildagliptin, vildagliptin / metformin hydrochloride idalgliptin, vildagliptin / metformin hydrochloride, vinblastine, vincristine, vindesine, dichloromethane, zcloplucinyl acetate , zuclopenhixol decanoate, zuclopentizole, αΐ-proteinase inhibitor (human), aamylcinnamaldehyde, and combinations thereof. The pharmaceutical composition can be of prescription or non-prescription substances such as vaccines. Exemplary non-limiting vaccines may be ex vivo expanded, characterized, viable autologous cartilage cells expressing proteins with specific markers, recombinant diphtheria, tetanus, acellular pertussis and hepatitis B combined vaccine, hepatitis A and hepatitis B combined vaccine, diphtheria conjugate vaccine , tetanus, pertussis, hepatitis B, and hemophilic influenza type b, vaccine against diphtheria, tetanus, whole cell pertussis and hepatitis B, Diphtheria, Tetanus, Acellular Pertussis, Recombinant Hepatitis B (Adsorbed), Inactivated Polio and Hemophilic Conjugate Adsorbed Vaccine, Diphtheria, Tetanus, Acellular Pertussis Vaccine, Recombinant Hepatitis B (adsorbed), Inactivated Polio, Hemophilic Conjugate B vaccine meningococcal) and hepatitis B (recombinant), hepatitis A (inactivated), hepatitis B (rDNA) (HAB), (absorbed) antigen vaccine, Hepatitis B vaccine (rDNA) (adjuvanted, adsorbed), Hepatitis B vaccine (recombinant), human papillomavirus vaccine, human papillomavirus vaccine [types 6, 11, 16, 18] (recombinant, absorbed), human rotavirus , attenuated, inactivated hepatitis A, purified recombinant HBsAg virus, influenza (virion fragmented, inactivated), influenza vaccine (surface antigen, inactivated, prepared in cell culture), Japanese encephalitis vaccine (inactivated, adsorbed), measles, mumps and rubella vaccine (live virus), measles, mumps, rubella and varicella vaccine (live virus), pandemic influenza vaccine, pandemic influenza vaccine (H1N1), (fragmented virion, inactivated, adjuvanted); Pandemic influenza A / California / 7/2009 (H1N1) vaccine v. pseudo-strain (X-179A) (surface-inactivated antigen, adjuvanted); pandemic influenza A / California / 7/2009 (H1N1) vaccine (v. pseudo-strain) (X-179A) (total virion, vero-derived, inactivated cells), pneumococcal polysaccharide conjugate vaccine, pneumococcal saccharide conjugate vaccine, adsorbed pre-pandemic influenza (H5N1) vaccine (fragmented virion, inactivated, adjuvanted), vaccine against rotavirus A / Vietnam / 1194/2004 NIBRG-14, shingles vaccine (herpes zoster) (live virus) and combinations of these.

Over-the-counter substances can be a vitamin or derivative of it, or a mineral compound or derivative thereof. The vitamin or mineral compound can be thiamine, thiamine pyrophosphate, riboflavin, flavin monocluteotic, flavin adenine dinucleotide, niacin, nicotinic acid, nicotinamide, niacinamide, nicotinamide adenine dinucleotide, tryptophan, biotin, folic acid , ascorbic acid, retinol, retinal, retinoic acid, beta-carotene, 1,25-dihydroxycholecalciferol, 7-dehydrocholesterol, alpha-tocopherol, tocopherol, tocotrienol, menadione, menaquinone, phylloquinone, naphthoquinone, calcium, calcium carbonate, calcium sulfate, calcium oxide, calcium hydroxide, calcium apatite, calcium citrate-malate, calcium gluconate, calcium lactate, calcium phosphate, calcium levulinate, phosphorus, potassium, sulfur , sodium, docusate sodium, chloride, magnesium, magnesium stearate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium sulfate, copper, iodine, zinc, chromium, molybdenum, carbonyl iron, ferrous fumarate, iron polysaccharide and combinations and derivatives thereof, without limitation. Derivatives of vitamin compounds include salts, alkali salts, esters, and chelates of any vitamin compound, without limitation. The over-the-counter substances can also be a herbal compound, herbal extract, derivatives or combinations thereof, without limitation.

The pharmaceutical composition can take any form and combinations thereof. Examples of such forms include, without limitation, chewable tablets, fast dissolving tablets, effervescent tablets, restorative powders, elixirs, liquid, solution, suspension, emulsion, tablets, multilayer tablets, bilayer tablets, capsule, soft gelatin capsule, capsule of hard gelatin, oblong tablet, lozenge, chewable lozenge, beads, powders, granules, dispersible granules, seals, cannula for vaginal irrigation, suppository, cream, topical, inhaler, aerosol inhaler, patch, particle inhaler, implant, slow release implant, lozenge, ampoule, ingestible substance, injectable, infusion, energy bar, liquid, food, nutritious food, functional food, yogurt , gelatin, cereals, cereal coating, feed or combinations of these. The preparation of any of the aforementioned forms can be carried out by means of

ES 2 525 262 T3 techniques and procedures well known and readily available to those skilled in the art.

The above-described objective and various other objectives are intended to be achieved in a third aspect of the invention by providing a method of accessing articles in a sequential manner comprising: providing a blister in accordance with the second aspect of the invention and administering to an animal.

Animal is defined herein as referring to all members of the animal kingdom including humans.

In some embodiments according to the third aspect of the invention, the animal is a female human, for example a pregnant, lactating, menopausal woman or a woman preparing to conceive a child or using contraceptive compositions.

The method of the present invention can be used by any human or other animal. The present procedure is particularly indicated for individuals with special therapeutic needs, or specific therapeutic needs, particularly when those needs would be beneficial through a complex therapeutic regimen. For example, without limitation, the present method is particularly indicated for menopausal women, lactating women, pregnant women, men or women planning to conceive a child, individuals afflicted with a pathological disorder, or any combination of the above situations.

The present inventive subject matter includes a method for providing optimal therapeutic support to an animal by increasing compliance with a complex dosing regimen and facilitating the simultaneous administration of incompatible substances in storage. The present inventive subject matter also encompasses a method of increasing patient compliance for prescription therapeutic substances.

The prescription substance may be, without limitation, a hormone replacement agent, a contraceptive agent, an osteoporotic agent, a chemotherapeutic agent, an anti-infective agent, an analgesic, a spheroid, an appetite suppressant, an agent for loss weight loss, a tobacco antagonist, a cholesterol reducer, or a combination of these. The prescription therapeutic substance may be a therapeutic regimen, that is, a complex daily therapeutic regimen.

The methodology of the present inventive subject matter is not strictly limited to the blister. Any conventional pharmaceutical packaging that exhibits a structural similarity to the blister is suitable. Exemplary non-limiting packages include tubes, bottles, packets, and the like.

The invention having thus been described, it will be apparent that it can be modified in many ways. Such variations should not be construed as a departure from the spirit and scope of the invention, and all such modifications are intended to come within the scope of the appended claims.

The methods of the invention may also comprise the provision of markings on the blister in accordance with the second aspect of the invention.

Although the present invention has been described with specific embodiments, it should not be construed as being limited in any way to the examples presented. The scope of the present invention is set forth by the appended set of claims. In the context of the claims, the terms "comprising" or "comprises" do not exclude other possible elements or steps. Likewise, the reference mention such as "one" or "one," one, etc. it should not be interpreted as excluding a plurality. The use of reference signs in the claims with respect to the elements indicated in the figures should not be construed as limiting the scope of the invention. Likewise, the individual characteristics mentioned in the different claims may possibly be advantageously combined, and the mention of these characteristics in different claims does not exclude that a combination of characteristics is not possible and advantageous.

Each of the first, second, and third aspects of the present invention can be combined with any of the other aspects. These and other aspects of the invention will become apparent and will be elucidated with reference to the embodiments described hereinafter.

A plurality of preferred and / or optional features, elements, examples and implementations will be summarized below. Features or elements described in relation to one embodiment or aspect may be combined with or applied to other embodiments or aspects where applicable. By way of example, a feature or item described in relation to the opening system can be implemented as a step in the procedure when appropriate. Also, explanations of the underlying mechanisms of the invention as practiced by the inventors are presented for explanatory purposes, and should not be used in an ex post analysis to deduce the invention.

Brief description of the figures

ES 2 525 262 T3

The system according to the invention will now be described in greater detail with reference to the attached figures. The figures show a certain way of implementing the present invention and should not be construed as limiting other possible embodiments that are included within the scope of the set of appended claims.

Figure 1 shows a side view of a blister according to an embodiment of the invention.

Figure 1a shows a side view of a blister according to an embodiment of the invention after removal of the first opening element, which allows access to the first depression.

Figure 2 shows a front view of a blister according to an embodiment of the invention.

Figure 2a shows the opening sequence according to the embodiment of the invention in Figure 2.

Figures 2b, 2c and 2d show other embodiments according to the invention that have a different opening sequence.

Figure 3 shows a front view of a blister according to another embodiment of the invention.

Figure 4 shows a side view of a blister according to another embodiment of the invention.

Figure 4a shows a side view of a blister according to an embodiment of the invention after removal of the first cover sheet, allowing access to the first depression.

Figures 5 and 5a show a side view of a blister according to an embodiment of the invention, where the support sheet comprises a rigid structure.

Figures 6 and 6a show a side view of a blister according to an embodiment of the invention, where the support sheet comprises a rigid structure and the support has at least one depression on the upper part and at least one depression on the bottom of the bracket.

Figure 7 shows a front view of a blister according to another embodiment of the invention, comprising a grip flap.

Figures 8a, 8b and 8c are different flap configurations that can be used to better grip the cover sheet.

Figures 9, 10 show blisters according to another embodiment of the invention.

Figure 11a schematically shows a top view of an embodiment of the invention.

Figure 11b shows different embodiments having different arrangements of the flaps and cavities.

Figures 12a and 12b schematically show a top view of an embodiment of the invention in which part of the cover sheet is removed during or after the drilling process.

Figure 13a schematically shows a top view of an embodiment of the invention in which parts of the cover sheet are kept unsealed.

Figure 13b shows a cross section of the embodiment of the invention of Figure 13a.

Figure 14a schematically shows a top view of an embodiment of the invention in which the backing sheet is in an unfolded state.

Figure 14b schematically shows a 3D view of the embodiment of the invention of Figure 14a in its folded state.

Figures 15a, b, c, d show an alternative embodiment based on the same folding principle as that of Figures 14a and 14b.

Figures 16a and 16b schematically show a 3D view of the embodiment of the invention of Figures 15a, b, c, d before or after fixing a support ring, respectively.

Figures 17a, b, c and Figures 18a and 18b schematically show a top view and a top view

ES 2 525 262 T3

3D of an embodiment of the invention having an integrated cover cap.

Figures 19 to 23 show examples of packages where the location of the cavities on the surface of the backing sheet is to provide optimal structure to increase the rigidity of the package and support the desired sequential opening.

Detailed description of the embodiments

Figure 1 shows a side view of a blister according to an embodiment of the invention. The blister is shown containing a series of 4 depressions in its backing sheet. This is simply for descriptive reasons and should not be considered as a limitation to the scope of protection. Any number of commercially practicable depressions can be produced in a single blister.

The blister is characterized by a support sheet 1 in which at least two, but preferably a plurality of depressions 2-5 of the support sheet 1, extending from the plane of the support sheet 1, are present to accommodate pharmaceutical compositions in different forms, for example capsules, tablets or lozenges.

The blister also includes a plurality of cover sheets 6-9 at least partially sealed on the support sheet 1 and around the respective depressions 2-5, with the function of regulating access to the depressions 25 that house the pharmaceutical compositions.

Cover sheets 6-9 are characterized in that the previous sheet partially overlaps the next one in order to provide a predetermined and sequential access to the depressions 2-5 and, therefore, to the pharmaceutical compositions contained therein.

In some other embodiments (not shown) the previous cover sheets completely overlap the following.

The support sheet 1 may also have one or more recesses 10-13 that are adjacent to each respective depression 2-5. In figure 1 the first recess 10 is shown as a stepped recess with the function of leaving a small portion of the edge of the cover sheet 6 unsealed. In this way a tab 14 is created.

By grasping the tab 14 of the cover sheet 6 by peeling off or tearing the tab 14, the cover sheet 6 is pulled up and back following the arrow 18 and thus removed providing access to the first depression 2 containing a pharmaceutical composition.

After removal of the cover sheet 6 as shown in figure 1a, the depression 2 opens, and access is obtained to the tab 15, that is, to the area of ​​overlap between the cover sheet 6 and 7, to remove cover sheet 7. A second recess 11 may be present to allow the tab 15 to be gripped so that, by peeling off or tearing the tab 15 the cover sheet 7 is pulled up and back following the arrow 19 and the cover sheet 7 removed allowing access to depression 3 and so on.

Although shown as an indentation within the backing sheet, in this example, the recessed areas may have different configurations and shapes.

In another embodiment, one or more recesses may not be present so that gripping the cover sheets may be feasible by leaving a small portion of the cover sheet unsealed around part of the edges of the respective depressions. The small portion may, in general, correspond to the area of ​​overlap between the cover sheets or to the tongue present in the aforementioned embodiment.

Figure 2 shows a blister pack according to an embodiment of the invention.

Although 16 depressions are shown in this embodiment, this is for descriptive reasons only and should not be construed as a limitation of the scope of protection. Any number of commercially practicable depressions can be produced in a single blister. Figure 2 shows the front view of the container of Figure 1. Access to the different depressions is obtained in a sequence that can be predetermined by providing a specific overlap of the cover sheets. As shown in Figures 1 and 1a the overlap areas 15-17 between the cover sheets 6-9 determine the access sequence. Figure 2 also shows a cover sheet 20 and a tab 21. The cover sheet 9 makes access to the tab 21 difficult, so that, upon removal of the cover sheet 9, the removal of the cover sheet 20 follows, allowing access to the depression 22. Consequently, the cover sheet 23 can be removed by peeling or tearing the tab 24 which is accessible only after removal of the cover sheet 20. In fig. 2a, the sequence of access to the different depressions, following arrow 25, is obtained using an overlap between the cover sheets and the tongue, as shown in fig. two.

ES 2 525 262 T3

Various opening directions can be obtained by a predetermined overlapping sequence, for example rounded, zigzag, top to bottom, left to right. Two examples are shown in Figure 2b and Figure 2c following arrows 26 and 27, respectively. A third example showing multiple observation points, indicated by arrows 28-31, is shown in Figure 2d.

Figure 3 shows a blister according to another embodiment of the invention, in which the first cover sheet 33 has a tab 32 extending over the edge of the support sheet 37 (Figure 4). This allows the patient to grasp the sheet without the need for a recess.

In another embodiment, the patient's grip on the first cover sheet of the blister can be achieved by using a cover sheet that does not extend beyond the edge of the support sheet and leaving a part of the cover sheet partially unsealed along its edge.

Similar to that shown in the previous embodiment, access to the depression 34 is obtained by removing the cover sheet 33 by grasping and pulling and thereby detaching the tear-off tab 32. As shown in the figures 4 and 4a, removal of cover sheet 32 ​​also provides access to the next tab 35 for removal of the next cover sheet 36.

In another embodiment of the invention, the blister support sheet comprises a rigid structure as shown in Figures 5 and 5a and in Figures 6 and 6a. A rigid structure can be a structure with the characteristic of presenting firmness, having a certain degree of rigidity, non-deformability and inflexibility to allow safe handling in transport, for example by means of normal mail shipment avoiding unwanted breakage. Depressions can be produced by different techniques, for example embossing, injection molding, calendering, molding or other thermoplastic or pressure treatment and the recesses between the depressions may (Figure 5) or not (Figure 5a) be present.

In some embodiments according to the second aspect of the invention, the at least one depression adapted to house pharmaceutical compositions on the upper part and at least one depression adapted to house pharmaceutical compositions on the lower surface of the support sheet are located off center with respect to each other in a meshed manner

In some other embodiments according to the second aspect of the invention, the support sheet comprises at least two pivotally connected halves each comprising a depression adapted to house pharmaceutical compositions, and in which the at least two halves are made from a single foldable sheet in a folded configuration thereby obtaining the rigid structure.

In some embodiments, the at least one depression on one of the at least two halves of said support sheet is located off-center with respect to the at least one depression on the other of the at least two halves so that the depressions are mesh when the two halves are folded into the folded configuration.

In other embodiments, the rigid structure is a solid block of material, for example the structure between the depression is not hollow. For example, in Figure 5 the backing sheet 48 may be a block of material, that is, a hard, solid piece of material.

In some other embodiments, the backing sheet has at least one depression on the top and at least one depression on the bottom surface of its surface, as shown in Figure 6.

In some embodiments, the rigid structure is or comprises an internal hollow structure. In some embodiments, the rigid hollow structure can be internally filled with air or other gases, for example inert gases. For example, in Figure 6 the support sheet 49 is a hollow rigid structure, that is, there is no material present between the depressions of the support. When the structure is hollow, support means may be present to provide rigidity, for example support elements 50-57 of Figure 6a.

In some embodiments, the at least two cover sheets are protected by at least one cover. Herein, the cap is defined as a removable film, thin sheet, rigid sheet, panel, or a hollow body that protects the cover sheet from unwanted rupture.

In some other embodiments, the cap may also comprise a form with information of interest to the patient, for example instructions for use of the contained pharmaceutical compositions, or an advertisement with related medications.

In some other embodiments, this information of interest to the patient may be printed, embossed, carved, stamped or etched on the internal or external surfaces of the at least one lid.

ES 2 525 262 T3

The at least one lid may be made of plastic, plastic laminates, plastic / paper laminates, or mined from thin plastic / metal or metal foils. Exemplary suitable non-limiting plastics for the backsheet are laminates containing PVC, polyamides, polyolefins, polyesters, polycarbonates, Teflon, and combinations thereof. The at least one cap can also be made of a material that is at least partially transparent in the field of visible light to allow visual inspection of the pharmaceutical composition contained in the cavities of the backing sheet.

In some embodiments, the at least one cap is completely removable. In other embodiments, the at least one cover can be opened by means of a rotation of the cover by at least one rotational joint located on the support sheet.

In some other embodiments, the at least one cover is or comprises at least one adhesive element, such as a long thin piece of plastic, cloth or paper with bonding capabilities, for example a piece of tape. In those embodiments, access to the cover and the backing sheet can be obtained by rotating the cover along one of the edges of the backing sheet.

The various cover sheets leading to the access of the depressions according to the opening system of the invention for the packages shown in Figures 6 and 6a are not shown in these figures solely for the sake of simplicity.

In some embodiments, the backing sheet further comprises at least two rim areas each of which surrounds one half of the backing, the ridges protruding in a perpendicular direction to the cover sheet and being adapted to fit together when the blister it closes.

In some other embodiments, an outer thin sheet is attached to areas adjacent to the flanges on a surface of the backing sheet that is the outer surface of the package when the package is closed.

In some embodiments, the rigid structure can be obtained, for example, by a support 210, as shown in Figures 14a and 14b. The support 210 can be produced in a single thin sheet in which two halves 211, 212 can be identified, each comprising cavities 207 arranged in rows. Figure 14a and Figure 14b show the holder 210 in an unfolded and folded state, respectively. The two halves 211, 212 are adapted to be folded such that the cavities 207 mesh with each other and thereby provide both rigidity and compactness to the support 210. The support 210 is preferably folded along two fold lines 213 so that the closed end of the cavities 207 are located on the opposite half, that is, the closed end cavities 207 of the half 211 are located on the middle 212 and vice versa, as shown in Figure 14a following arrows 230. Said design results in a holder 210 in which the pharmaceutical compositions are arranged to be accessed from both sides of the holder 210. The cavities 207 are covered by a sheet 208 as previously described; preferably, the same cover sheet covers both halves 211, 212; It could be the case that two separate cover sheets cover each half 211, 212. The cover sheet 208 is preferably sealed to the support 210 before folding, but in principle it can also be fixed before the support is folded. 210. In Figures 14a and 14b, the cavities 207 are honeycomb-shaped and arranged in two rows on each half 211, 212, of the holder 210. This configuration provides additional rigidity to a flexible blister structure once folded. In general, in the folded state, the closed bottom of the cavities 207 of the half 212 can support a corresponding area on the half 211 and vice versa. Any other configuration of the mesh cavities can be envisaged which in the folded state can support the backing sheet and provide rigidity to the final structure. Likewise, the rigidity and therefore protection of the pharmaceutical composition arranged in the cavities 207 is provided by the edge portions 214 which are formed to provide barriers and support to the support sheets along the edges of the bracket 210 when folded. Other configurations and arrangements that serve the same purpose are also within the scope of the present invention. The fact that the two halves 211, 212 are made from a folded sheet of material rather than using two separate sheets, means that they are held in a more fixed relationship to each other which increases the rigidity of the support 210. To prevent support 210 from unfolding, the two halves 211, 212 of support 210 can be joined by adhesive tapes 215, such as hot melt adhesive. Such a joint will further prevent the mutual displacement of the two halves 211, 212 and thereby also provide additional rigidity to the support 210.

Also, the placement of the cavities on the surface of the support sheet can be optimized, for example, by empirical procedures, to provide an optimal structure that supports the rigidity of the container and the desired sequential opening. For example, Figures 19 to 23 show examples of packages in which the locations of the cavities on the surface of the backing sheet can provide an optimal structure to increase the stiffness of the package and follow the desired sequential opening, for example by following the numbered cavities. For example, in Figure 19, the different location of the cavities, for example, 301 and 302, can also be coupled to a different location and design of the cutout, for example 304 to remove the

ES 2 525 262 T3 cover sheet and gain access to the cavity located below. Reference numeral 303 identifies the adhesive area that connects the lower and upper surfaces of the backing sheet carrying the blisters, for example 301 and 302. Figures 20 and 21 show two embodiments of the medical package with cavities and cutouts having an alternative configuration. In figure 21 small bulges 305 are present between the cavities, for example 306 and the cutout, for example 307.

Figures 22 and 23 show further embodiments of the medical package with different combination of cavities, for example 308, 310 and cutouts, for example 309. Thus a desired sequential opening can be obtained.

Figures 15a, b, c, d show an alternative embodiment on the same folding principle as Figures 14a and 14b. Figure 15a shows the unfolded support 210, where the dashed lines 216 show the configuration of the support 210 of Figure 14a. The embodiment of Figures 15a, b, c, d is provided with projecting ridges 217 along the edges. The sheet intended to become the support 210 and the ridges 217 is typically formed by thermoforming a plastic sheet. After thermoforming with the configuration of Figure 15a, the sheet is formed by the dashed lines 216 around the two halves 211, 212 that comprise the cavities 207. The two halves 211, 212 are folded along arrows 230, as shown in Figure 14a, to achieve the folded structure, as shown in Figure 15b, which would leave the spaces between the flanges 217 as holes. To obtain the closed outer surfaces of the container, an outer thin sheet material 218, for example a plastic sheet, is attached to the flange areas 217, preferably before folding. The connection of the outer thin sheet 218 and the flange area 217, and therefore with the support 210, is shown in Figure 15c, and the resulting appearance is seen in Figures 15b, and 15d in the open and closed states. , respectively. In this way, the support 210 and, therefore, the pharmaceutical compositions will be protected by the sections 219 that comprise the ridges 217 and the outer thin sheet 218 that will function as lids. If additional stiffness and an even more closed design is desired, this can be obtained by adding an additional ring 220 on top of each flange 217. This is shown in Figures 16a and 16b before and after ring attachment, respectively. . Ring 220 can be attached by any appropriate means, such as by adhesive or press fit.

In one embodiment, the support 210 including the ridges 217, after perforation along the dashed lines 216, filling with the pharmaceutical composition and the additional covering by the aluminum film 218, is folded without the ridges spacer 217 and bracket 210. Upon opening of the blister, the aluminum film 218 sealed over the flanges 217 will act as lids and the package is opened along the dashed lines 216 that have been perforated following the thermoforming process. In this way, an additional rigidity of the structure is obtained since the breaking of the lines 216 is only achieved after the first use of the container, to avoid an unwanted opening during transport from the manufacturer to the first user of the container.

A first step in a currently preferred manufacturing method for the embodiment of Figures 15a, b, c, d would be to shape the sheet comprising the supports 210 and the flanges 217 to the geometric configuration shown in Figure 15a. Typically this would be done first by thermoforming a plastic sheet. The cavities 217 are then filled with the pharmaceutical compositions, and the cavities 207 are covered by a cover sheet 208, typically made of aluminum foil. The next stage is drilling in which the support halves 211, 212 are separated from the rim areas 217. In the same stage or in a subsequent drilling stage, the flaps 201 can be manufactured as described above, for example in relation to figures 11a, b. Next, the outer thin sheet 218 is attached to the flange areas 217 as shown in FIG. 15c. The outer thin sheet 218 can be sealed and / or attached, by heat welding or by adhesive. The outer thin sheet 218 may be a continuous thin sheet that provides additional protection to the cover sheet 208 so that no access to the cover sheet 208 is possible unless the outer thin sheet 218 is removed after removal. container opening.

In some embodiments, the outer thin sheet 218 may have the desired configuration prior to attachment to the rim area 217, or it may be attached as a sheet material covering a large number of containers so that it has to be perforated adopting the desired configuration after fixing.

All the steps described so far can be carried out without the need to rotate the material, which is advantageous from a manufacturing point of view. The following steps are preferably performed after rotating the containers through an angle of 180 ° so that what was previously the bottom face turns out to be the top face. If desired, adhesive is applied, such as hot melt adhesive tapes, and if desired, thermoformed plastic rings 220 are arranged on top of the flanges 217. The two halves 211, 212 of the holder 210 they are then folded together and attached, and the "caps" comprising the flanges 217 with the outer thin sheet 218 are closed around the support 210. If desired, instructions for use of the pharmaceutical compositions may be provided within the container; may, for example, be adhered to the inside of the outer thin sheet 218 before the container

ES 2 525 262 T3 is closed.

An alternative medical package having an integrated cover cap will now be described with reference to Figures 17a, b, c and 18a, b.

The blister according to one aspect of the invention comprises at least four sections arranged in a row and manufactured from a single sheet, each section being pivotally connected to at least one of the other sections along a line of folded on the individual sheet.

By individual sheet is meant a continuous sheet of, for example, plastic.

Each of the two intermediate sections of said at least four sections may constitute a support half containing at least one depression adapted to house pharmaceutical compositions, the two halves being pivotally connected to each other. Each of the two end sections of said at least four sections may constitute a part of the outer cover for at least one of said support half, each of the two end sections being pivotally connected to the corresponding support half.

Corresponding is defined herein as one half of the complementary support according to Figures 17a, b, and 18a and 18b.

The at least four sections are adapted to be folded into a folded configuration in which the two halves of the bracket are positioned adjacent to each other with the depressions engaged and with the open sides of said depressions facing opposite each other.

In this way each of the outer cover parts is positioned adjacent a support half.

The design is based, in the first stage, on the thermoforming of a plastic sheet with the configuration shown in figure 17a. The sheet comprises a support sheet comprising two support halves 211, 212 corresponding to those in Figure 14a. The sheet further comprises, at the two distal ends of the support halves 211, 212, two outer cover portions 221. These parts 221 are an extension of the support halves when thermoforming has been carried out to obtain the ridges but not the cavities that hold the pharmaceutical compositions. It can be seen as an advantage that a single thin sheet of plastic material can be thermoformed to identify parts that have different functions, for example to contain a pharmaceutical composition or to provide additional protection to the cover sheet that protects the cavities without have to change your orientation. The plastic sheet is then folded into a container as shown schematically in the side view of Figure 17b by folding along the fold lines 222 shown in Figure 17c. In its folded state, the blister shows only the two cover portions 221, as shown in Figure 18a. When ready for use, it is possible to gain access to one side of the holder 210 only by opening one of the outer cover portions 221 (not shown). Fig. 18b shows the container in a state in which both outer cover parts 221 are partially open. An advantage of this embodiment is that the supports 210 and the outer cover portions 221 are made from the same sheet of material and no additional cover is needed except for the cover sheets to cover the pharmaceutical compositions in the cavities. 207.

In some embodiments, a larger capacity medical package can be obtained by arranging more than two carrier halves in a row, which halves are then folded together and preferably adhesively bonded two by two. Thus, a double, triple or multiple structures can be achieved in which each of two support halves can be joined two by two. In this configuration, the two distal ends, that is, the outer covers provide a cover for the outermost support halves.

In a multiple structure, the sequential opening can be achieved as in the single structure described. A further advantage may be that an increased number of cavities may become available to contain pharmaceutical compositions.

In some embodiments, the unsealed tab, which provides a better grip for peeling or tearing the cover sheet and accessing the depressions, can be a flap, for example a strip, or a cutout. Figure 7 shows a blister according to another embodiment of the invention comprising a flap.

The specific profile of the flap is linked to its function. The flap can have any shape and size that allows it to be gripped by a person or mechanic by the method described by the invention and for tearing or peeling off. Although in this embodiment the element is shown in a triangular shape, in other embodiments it may take different shapes, for example circular or square.

ES 2 525 262 T3

Figures 8a, 8b and 8c show different grip flap configurations that can be used to better grip the cover sheet.

In some embodiments, the element, for example a flap, can be made of a non-slippery material, such as rubber or it can have a certain degree of roughness to provide a better grip and to be more easily gripped, torn or taken off.

In some other embodiments it may have a configuration that is easily accessible by a user, for example resembling a pad to provide a better grip for the user after use.

The flaps in this embodiment are shown on a specific edge of the cover sheet. In other embodiments they may be located at different locations along the edges of the cover sheets.

By placing the flaps in different areas of the cover sheets, different opening sequences are possible.

In some other embodiments, the first flap may have a locking function such that upon removal of the first flap, access to the next flap and cover sheet is achieved without exposure of the first depression on the sheet. of support.

Although the number and shape of the depressions in the containers is shown with a specific shape, that is, 16 cylindrical depressions, in other embodiments the container may have fewer or more depressions and may have other shapes, for example cubic, pyramidal or spherical.

Figure 11a schematically shows a top view of an embodiment of the invention in which a flap 201 is arranged next to each cavity 202. The flaps 201 are obtained by leaving the areas located below each flap 201 not sealed during manufacture when the cover sheet is attached to the backing. In a preferably later process step, the edges 203 of the flaps 201 are separated from the sealed portion 204 of the cover sheet, typically by perforation. The perforation can be through the cover sheet only, or completely or partially through the backing as well. An advantage of drilling through the cover sheet alone is that the backing remains intact and therefore more rigid and less prone to failure. An advantage of allowing drilling to be completely or partially through the holder is that tolerances on drilling tools and drilling action can be less tight. Figure 11b shows different embodiments having different arrangements of the flaps and cavities.

In an alternative embodiment to those shown in Figures 11a and 11b, selected parts of the cover sheet are removed during or after the drilling process. An example of such an embodiment is shown schematically in Figures 12a and 12b. The part of the cover sheet that is removed is marked 205 in the figures. This process can result in the flaps 201 being easier to grip. As shown in Fig. 12b, the cover sheet may project over the edges of the holder, for example by an amount corresponding to the size of the flaps 201 and the parts 205 of the cover sheet that are being removed. In this way, the flaps 201 can even be easier to grip than when overlapping the support.

In yet another embodiment shown schematically in Figures 13a and 13b, parts of the cover sheet are left unsealed to the support as in the embodiment of Figures 11a and 11b. The embodiments differ in that, in that shown in Figures 13a and 13b, the manufacture does not include the provision of the flaps 201 by perforation. Instead, there is a recess 216 following each cavity 207 and to gain access to the contents of a cavity, the cover sheet 208 is pressed into the recess 206 and the cover sheet 208 is withdrawn from above. cavity 207. This action is typically carried out using a finger 209, but an appropriate tool could also be used. In this embodiment, the cover sheet 208 is preferably sealed to the backing along the entire area that does not constitute a recess 206 or a cavity 207. An advantage of this embodiment is that no drilling step is required. in the manufacturing process. Figure 9 shows a further embodiment of the invention in which the blister includes four cover sheets 44-47, each allowing multiple access to 4 depressions. For example, removal of the cover sheet 44 by gripping the flap 38 up and back provides access to the depressions 39-42 simultaneously. In this way, a multiple distribution of the pharmaceutical composition present in the depressions is achieved since by means of a single removal of the cover sheet, several depressions are accessible. Removal of cover sheet 44 also provides access to flap 43 which, in turn, allows removal of cover sheet 45 allowing access to the next 4 depressions.

Multiple dispensations can be very convenient for specific diseases. For example, this may be particularly advantageous as a convenient, simple and effective way to facilitate the simultaneous administration of

ES 2 525 262 T3 incompatible substances in storage particularly when said substances are taken as part of a complex daily sequential therapeutic regimen.

Figure 10 shows another embodiment in which removal of the first cover sheet provides simultaneous access to 2 depressions and the flap to remove the next cover sheet. The advantage is also that it facilitates the simultaneous administration of prescription and non-prescription substances as part of a complex regimen.

Although the present invention has been described in conjunction with the specific embodiments, it should not be construed as being limited in any way to the examples presented. For example, the support has been described as manufactured by thermoforming a plastic sheet. However, other manufacturing processes, such as thermoplastic molding, are also covered by the scope of the present invention. The materials can also differ so that the parts of the containers can be made, for example, of polymer foam, composites or paper-based materials, such as cardboard. Correspondingly, other joining procedures in addition to those mentioned are also covered; such procedures will be well known to those skilled in the art. Any of the embodiments can be provided with opening and closing means as shown in the figures. Other possible designs of closing and opening means will also be recognized by the person skilled in the art.