MXPA00001740A - Drain system containing additives - Google Patents

Abstract

The invention relates to a device containing additives intended for cutaneous application, characterized in that it consists of a) an additive flow line which clearly overhangs over the flow line on both sides, c) a back layer on one side if the flow line of the system does not fulfill the back layer function, and d) a removable protective layer on the other side.

Description

MATE SYSTEMS CONTAINING ACTIVE PRINCIPLE Description of the invention: The invention relates to wick systems with pharmaceutical / hygienic / cosmetic applications and a method for their manufacture. The term "wick" indicates that it is a cord-like structure, which can be rolled up and with which the active ingredient can be combined before manufacturing the active principle system. This cord may be constituted by a unitary material or a mixture of materials. The active ingredient can be alone or in the form of an active ingredient preparation. The active principle may be dissolved in the cord. If it is a solid active substance, an auxiliary substance can also be dissolved in the active principle. Both alternatives may be convenient to achieve a useful consistency - for example sufficient breaking strength - or to improve diffusion properties. It is also possible that the cord has a microporous or even macroporous structure. The important thing is that the active principle can be emitted from the cord to its surroundings. The cord is preferably flat, although it can also be a round wick, in which case the active ingredient can be stored, in the usual way, in the capillaries and transported therethrough. REF .: 32876 The important thing is that the cord of active principle in the manufacture of the products according to the invention can be applied in a continuous process, for example with a roller, which can be a coil or any storage container on the patches or the systemic cords and that the separation can then be carried out in a continuous process, for example with the aid of a cutting tool or roller, simultaneously with the separation of the patch.

In conventional systems, the active principle is in a discrete space, for example in a deposit in the form of a flat bag or in the entire layer on the support sheet (matrix patch); A whole series of variants and mixed forms is also known. In the cases in which a layer containing the activated principle is formed, problems arise nevertheless: 1. A dough has to be made by adding solvents and / or a plasticizer, in which incompatibilities of the active principle and the dough or the adhesive mass, the resin and the solvents can arise, among others. This is especially problematic when several active ingredients are used and also a plasticizer, agents that promote skin permeation (Enhancer) and / or similar additive substances. 2. It is possible to remove a relatively volatile active ingredient - when drying the system. 3. If the active substance is toxic or photosensitive, additional protective measures must be adopted that are costly. 4. In systems of thermoplastic adhesives, in which the active principle is incorporated in the mass, it is possible that the active principle is modified or suffer negative influences due to the high temperature of the melt.

. The contribution of the support and the dosage of active principle and / or active ingredient support can generally only be carried out at technically costly stages. The same can be said when applying first on the band - as in the "tablet patch" - a support, as a non-woven material and then the active principle on the latter. 6. Also in the "bag / membrane systems", the mass of active ingredient can not usually be applied continuously and must be "projected" separately or together with a support mass intermittently or added from any other form, intermittently. 7. In other methods of manufacture, in any case, continuous - for example multi-channel systems - it is necessary to seal surfaces together and therefore the problem of the possible incidence of the active principle on the sealing surfaces still exists.

What is intended with the present invention is therefore to ensure the continuous incorporation of the active principle on or into a material in the form of a cord, from which the systems are further separated. "Cord" is understood as narrow bands, although the cord of active principle is less broad than the systemic cord.

The problem is solved, according to the present invention, by having the active principle applied alone or suitably, on a thin primary support, in the form of a cord, with absorbing properties or other similar absorption properties, due to the chemical nature, possibly in the form of a solution, comparable to the introduction in a wick. This product is hereinafter referred to as the active principle cord.

The object of the invention is a) a cord of active principle b) a systemic cord, wider, that clearly protrudes from the cord of active principle on both sides and c) in the case that the systemic cord does not act as a layer rear, on one side, a back layer and, d) on the other side, a separable protection layer.

Thus, a subject of the invention is a method for the introduction of active principles in systems for cutaneous application, introducing the active principle in a support, characterized in that the active principle is introduced continuously into a support or it is applied on it, thus obtaining a cord of active principle, the cord thus obtained is combined with a wider systemic cord, which clearly protrudes from the cord of active principle on both sides, this system is provided, on one side, of a separable protection layer and, in case the systemic cord does not act as a back layer, of a posterior layer, of the other side, and the combined cords are separated so that appreciable quantities of principle can not leave the edges. active.

The separable protective layer is therefore present in any case, regardless of whether the systemic cord acts as a back layer or not.

The invention relates in particular to a method for the continuous introduction of active principles into thin systems, preferably large surfaces, continuously manufactured as wafers or patches of active principle, incorporating the active principle into a bead of active principle and applying said cord to a systemic cord and / or applying a systemic cord to a cord of active principle and providing the definitive system with a separable protective layer and eventually a posterior layer, as well as the products that are manufactured according to this method. These systems may also have a membrane for controlled emission.

The active principle can be applied as such or in the form of a preparation of active ingredients, for example by immersion, printing or in any similar way on or on the support in the form of a cord. It is also possible to generate a mass, in which the active principle is incorporated, and extrude said mass, possibly applying it dire on the systemic cord, forming a cord of active principle, for example by projection or extrusion or from the strands. extruded, spun, weave threads or fibers, also laces containing active substance or assemble them - as non-woven material -.

You can also pour the dough - using solvents, in the form of hotmelt or powder form as in the coating - on the systemic cord, eventually dry, let cool or fix by energy input or generate in situ, cut into cord and subsequently apply "from the roller".

The active substance cord can also be formed or constituted by fibers also loaded with active principle, tissues, non-woven materials or suitable substances - also polymers. Examples of suitable active substance carriers are conventional plastics, such as polymers, copolymers and block copolymers based on polyisobutylene (PIB) ethylene vinyl acetate (EVA), polyacrylates or acrylate resins, silicones, styrene block copolymers. - isobutyl - styrene (SIS) and others. The specialist knows these support materials used in cutaneous or percutaneous systems by: to). Martin C. Musolf: "Pressuré-Sensitive Adhesives: Science and Engineering "in Transdermal Controlled Systemic Medications, ed. by Y.W. Chien, Marcel Dekker Inc., New York, 1987, p-93-112 b). "Handbook of Adhesives", ed. by Irving Skeist, Van Nostrand Reinhold, New York 1990, 3rd edition.

In flat systems for oral use, such as wafers, for example hydroxypropylcellulose, methylcellulose, starch or modified starch can be used.

The active substance support is applied in a continuous process according to a preferred embodiment in a cord on the systemic cord and is dimensioned, in a working phase, by separating / cutting the individual systems. There are many possibilities for this: 1. The "systemic cord" is conveniently constituted by one or more sheets of plastic and / or aluminum optionally coated by gluing. By applying the active principle cord on a sheet and coating by sticking with the systemic cord, the cord of active principle can be enclosed between the sheets. 2. The cord of active principle can be applied "from the roller" on the systemic cord. 3. Application of the cord of active principle on a systemic cord, which serves as the back layer of the system. 4. Apply on an adhesive layer, which is on a protective sheet.

. Coating the active substance bead with a thermoplastic adhesive coating, which also has adhesive property at normal temperatures or with an adhesive coating mass, which contains solvents on all the surface of the active ingredient bead and / or on the entire surface or part of the surface of the patch band. 6. Apply or extrude the cord of active principle directly on the systemic cord. 7. Formation of the back layer - support layer with one of these coatings that has the necessary properties as resistance and impermeability to the active principle. 8. Embed normal extruded threads. 9. Introduce several, possibly many cords of active principle in a systemic cord. In this way, a particularly homogeneous distribution of the active principle in the systemic cord is achieved, without adversely affecting the speed of production. This is a preferred embodiment, in which, according to a particularly suitable embodiment, the cords of active principle can be arranged parallel to the systemic cord and / or in the form of a loop to obtain samples, as in a tissue. This also improves the uniformity of the distribution.

. Combination of cords with different active principles, which are usually incompatible with each other or whose combination requires a particular complication. For example, the active principles contained in the matrix or the liquid of a membrane system can be united in the same concentration or in a different one with the active principles contained in the cord of active principle, such as for example physostigmine and scopolamine, estrogens and gestagens, to form a combined system. This is also a preferred embodiment. 11. According to another preferred embodiment, the cords of active principle can be combined with different conventional systems such as full-surface matrix, membrane, etc., so that systems can be obtained simply on the surface or in the layers of the system. different, for example, concentrations and emission mechanisms to improve controlled emission; For example high-concentration cords can be introduced in layers far from the skin, others less concentrated in the layer close to the skin (or vice versa), so that at the beginning there is a low emission and subsequently higher (or vice versa) . 12. According to another preferred embodiment, photosensitive and / or toxic or slightly volatile active principles can be prepared, so that the active substance bead is encapsulated in whole or in part. These encapsulated materials must, of course, be permeable at least on one side to the active principle and the active substance bead must then be closed immediately after application, for example by applying an additional layer, for example by coating. 13. In case of sensitivity to the temperature of the active principle in the cord of active principle, in the elaboration with thermoplastic adhesives or in case of sensitivity to drying it can be done that the application of the active principle is carried out on the cord, in the opposite part to the liquid thermoplastic adhesive. In this case, the back layer of the active principle cord acts as a thermal insulator. 14. In some cases, when proceeding to the separation of the systems, a simultaneous or additional wedge-shaped pressure can be made, which closes the edges so that no appreciable amount of active principle can escape from them. In conventional systems, it is necessary to avoid active ingredients in high concentration at the edges. However, in practice, with the systems according to the invention, this precaution is almost unnecessary, since the transverse diffusion is reduced. It is therefore, in the present invention, to overcome a prejudice.

. In another preferred embodiment, the strands of active principle can also be applied in the form of a network of grids, mesh fabric and the like, continuously over the corresponding systemic strands (support, intermediate or adhesive layer). You can proceed so that a second active principle is integrated in the same way, for example 16. Applying two or more networks of grids with active principle on the systemic cord or the corresponding adhesive supports or layers.

For the invention, the most diverse active principles are suitable, and in particular the active principles of percutaneous application. Typical examples are: D Nicotine D Corticosteroid: hydrocortisone, Prednisolon, beclomethasone-propionate, flumetason, triamcinolone, triamcinolonacetonide, fluocinol, fluocinolin-acetonid, fluocinolonacetonidacetate, clobetasol-propionate, etc. C Analgesics, anti-inflammatories: acetaminophen, mefenamino acid, flufenamino acid, diclofenac, diclofena-sodium-alclofenac, oxifenbutazone, phenylbutazone, ibuprofen, flurbiprofen, salicylic acid, 1-menthol, camphor, sulindac-tolmetin-sodium, naproxen, fenbufen, etc. D Sedatives of hypnotic action: phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazepam, lorazepam, haloperidol, etc. J Opiates such as diamorphine, morphine base, morphine hydrochloride, dihydrocodeine, buprenorphine, fentanyl. I Tranquilizers: • flufenazin, thioridazin, lorazepam, fluniotrazepam, chloropromazin, etc. 2 Agents against hypertension: pindolol, indenolol, nifedipin, lofexinin, nipradinol, bucumolol, clonidin, bopindolol, bupranolol, etc. D Coronary-acting substances such as ISDN, nitroglycerin and their compounds. D Diuretics of hypertension reducers: hydrotiacid, bendroflumethiazide, cyclopentiacid, etc. J Antibiotics: penicillin, tetracycline, oxytetracyline, fradiomycin sulfate, erythromycin, chloramphenicol, etc. -J Anesthetics: Lidocaine, benzocaine, ethylammonobenzoate, etc. D Antimicrobial agents: benzalkonium chloride, nitrofurazon, nystatin, acetosulfamin, clotimazole, etc. G Anti fungal agents: pentamycin, amphotericin B, pyrrolnitrin, chlorimazole, etc. u Vinamines: Vitamin A, ergocalciferol, clolecalciferol, octotiamine, riboflavin burirate, etc. C Antiepileptics: Nitrazepam, meprobamate, clonazepam, etc. D Coronary dilator vessel: dipiramidol, erytritetranitrate, pentaritrit-tetanitato, propatiliti- nitrate, etc.

Antihistáminicos: diphenylhydramine-hydrochloride, clofenidamine, diphenylimidazole, etc. Q Antitussives: dertromettorfan (hydrobromide), terbutalin (sulfate), ephedrine (hydrochloride), salbutanol (sulfate), isoproterenol (sulfate, hydrochloride), etc. J Sex hormones: Progesterone, estradiol, testosterone, etc. D Timolépticos: Dosepin, etc. ü Other pharmaceutical products: 5-fluorouracil, 1, desmopressin, domperdon, scopolamine (hydrobromide) physostigmine, naltrexon, naloxon, peptides, etc.

Naturally, this relationship is not exhaustive.

The products manufactured according to the invention are suitable for cutaneous application, and in particular for percutaneous application on the epidermis or mucous membranes in all their forms. The application is also included as hygienic wafers, that is, wafers for oral hygiene. These are flattened systems that improve oral hygiene due to the action of active ingredients or combinations of active ingredients that clean the mouth and / or reduce odor or coat it.

These oral hygiene wafers are applied orally and can be completely dissolved in the mouth, although a peroral application is also possible, in which case rigid products are not used perorally but very plastic, whose components can be chosen in such a way that they dissolve completely in body fluids and can disintegrate physiologically.

These oral wafers can also contain pharmaceutical active ingredients instead of hygienic active ingredients.

The method according to the invention and the products thus obtained have a number of advantages. For example, speed in the production of systems can be increased, since intermittent production rhythms are not required, vertical movements with respect to the guide of the band of the system. The separation can also be carried out continuously - by means of rotating cutting rollers, with which a coining is also carried out at the edges. In addition, another special advantage is to improve the quality and avoid waste due to the absolute homogeneity of the distribution of the active principle in the cord, which can be checked before the manufacturing process begins. The problem of dosage, which usually occurs during manufacturing, is reduced because - if the cord is manufactured after having defined its geometry - the final dosage is made only by the length (or volume, length, surface and thickness) of the cord in the patch, preferably by the length of the patch with a defined width of the "patch band", i.e. of the systemic cord. Using coatings of thermoplastic adhesives, this method offers a special advantage, since the temperature, at the time of application is much lower than the temperature during the preparation of the dough, so it is more difficult to produce an alteration of the active principle in the cord.

The invention also has particular advantages in the case of conventional oral systems containing active principle (also flattened), since due to a higher concentration of active principle in the cord of active principle - which is simply introduced into the oral system containing the active principle, it is possible to compensate for the reduction in concentration that occurs in the outer surfaces and consequently the lower emission of active principle. This applies very particularly to the case where several strands of active principle are used, optionally also with various active principles and with different concentrations.

With the cords of active principle of the most diverse types, as to active principle, concentration and / or type of "wick" material, the desired shape in controlled release behavior can be influenced.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (20)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. Device containing active substance for dermal application, characterized in that it is constituted by a) a cord of active principle b) a systemic cord, which clearly protrudes from the cord of active principle on both sides and c) in the case that the systemic cord does not act as a back layer, on the one side, a back layer and, d) on the other side, a protective layer -separable.

2. Device according to claim 1, characterized in that it is closed at the edges by a wedge.

3. Device according to claim 1 or 2, characterized in that a membrane is present between the active principle cord and the systemic cord, on the one hand, and the separable protective layer on the other hand, on the other hand, controlled emission of active principle.

4. Device according to one or more of claims 1 to 3, characterized in that the active ingredient is dissolved in the cord or the active substance cord has a porous structure, in whose pores the active ingredient is stored.

5. Device according to one or several of claims 1 to 4, characterized in that the systemic cord is constituted by one or more sheets of plastics and / or aluminum, optionally coated by gluing.

6. Device according to one or more of claims 1 to 5, characterized in that the active principle cord is arranged parallel to the systemic cord, forming a right angle, diagonally or in the form of a loop.

7. Device according to one or more of claims 1 to 6, characterized in that it contains a combination of cords, with at least two active principles or concentrations of different active principles.

8. Device according to one or more of claims 1 to 7, characterized in that it contains cords of active principle with different conventional systems.

9. Device according to one or more of claims 1 to 8, characterized in that it is in the form of a thin system with a large surface, preferably a wafer or a patch of active principle, in particular for percutaneous application.

10. Device according to one or more of claims 1 to 9, characterized in that the active substance cord is in an encapsulated form, totally or partially enclosed within a membrane.

11. Method for the introduction of active principles in systems for the cutaneous application, combining the active principle with a support, which is characterized by the fact that the active principle is introduced continuously in a support or is applied on it, obtaining in this way a cord of active principle, the cord thus obtained is combined with a wider systemic cord, which clearly protrudes from the active principle cord on both sides, this system is provided, on one side, with a separable protection layer and , in case the systemic cord does not act as a posterior layer, of a posterior layer, on the other side, and the combined cords are separated so that appreciable amounts of active principle can not exit at the edges.

12. Method according to claim 11, characterized in that the cord of active principle is applied continuously with a roller on the systemic cord and • 5 then it is separated continuously.

13. Method according to claim 11 or 12, characterized in that the active principle is introduced into a support in the form of a cord, with properties 10 absorbers.

14. Method according to one or more of claims 11 to 13, characterized in that the active principle is combined with the material in the form of a cord, by means of 15 dip or pressure.

15. Method according to one or more of claims 11 to 14, characterized by the fact that the cord of? active ingredient is obtained by extruding a mass that 20 contains active ingredient and is projected (applied) on the systemic cord.

16. Method according to one or more of claims 11 to 14, characterized in that the cord of The active principle is obtained by applying a powder containing active ingredient and preferably applied to the systemic cord and solidifying by means of energy input.

17. Method according to one or more of claims 11 to 16, characterized in that the combined cords are separated forming patches.

18. Method according to one or more of claims 11 to 17, characterized in that the active principle cord is applied to a sheet and the product thus obtained is incorporated between the sheets with the systemic cord.

19. Method according to one or more of claims 11 to 18, characterized in that the active substance cord receives an adhesive coating or is encapsulated.

20. Variant of the method of claim 11, characterized in that a mass containing active ingredient is applied directly on the systemic cord, forming a cord of active principle, and the product thus obtained is further elaborated according to the method described in one or more of claims 10-17.