KR20010023134A - Drain system containing additives - Google Patents

Abstract

The active material-containing device for skin of the present invention comprises a) an active material strand, b) a system strand that prominently protrudes beyond the active material strand on both sides, and c) a backing on one side unless the system strand acts as a backing layer. Layer, and d) a removable protective layer on the other side of the system.

Description

Drain system containing additives

In conventional systems, the active material is present in a separate room, for example in the form of a flat pouch or bag, in the reservoir, or in the entire layer on a carrier sheet (matrix patch), many variants and mixtures are known. However, when the active material-containing layer is formed, the following problem arises:

1. It is probably necessary to produce the mass under the addition of solvents and / or emollients, and incompatibility may occur between the active and mass or adhesives, between the resin and the solvent. It is particularly problematic when various active agents and emollients, skin penetration enhancers (enhancers) and / or similar additives are used.

2. A relatively volatile active substance may be discontinued with the substance which is discontinued when the system dries.

3. If the active substance exhibits toxicity or photosensitivity, additional measures of protection involving considerable effort shall be taken.

4. In hot melt adhesive systems in which the active material is incorporated into the mass, the active material may be altered or adversely affected by the high temperature of the molten material.

5. Supply of Carriers and Dosing of Active Materials and / or Active Materials Carriers can usually only be achieved in technically complex cycles. It is also initially applied to the web, as in the case of "purified patches" -carriers such as nonwovens, and then the active material is applied onto the carrier.

6. Even in “pouch systems / membrane systems” it is not usually possible to add the active mass continuously, but instead must be extruded or spray coated in a cycle, alone or in combination with a carrier mass, or metered in the cycle.

7. In all other continuous manufacturing processes, eg multichannel systems, it is necessary to seal the surfaces together, while at the same time there is a problem of adverse effects on the active material on the sealing surfaces.

FIELD OF THE INVENTION The present invention relates to wick systems that can be used pharmaceutically / hygiene / cosmetics and methods for making the same.

The term "wick" refers to a stranded body that can be rolled up and to which the active material is bound prior to making the active material system. The strand may be made of a uniform material or a mixed material. The active substance can be present on its own or in the form of an active substance formulation. The active substance can be dissolved in the strand. In the case of a solid active substance, auxiliary substances may be dissolved in the active substance. Both methods are useful, for example, in obtaining sufficient tear resistance hardness or improving diffusivity. In addition, the strand may have a microporous or even macroporous structure. Importantly, the active substance can be released from the strand into the environment. Preferably, the strand typically contains an active substance stored in the capillary and carried through the capillary, and may be a flat or round wick.

In the manufacture of the product of the invention, the active strands can be used for patch or system strands respectively, for example from rolls (including spools) or other reservoirs, such as loop scrims in a continuous process, followed by continuous processes It is important in that it can be separated at the same time as the separation of the patch, for example using a punching tool or punching roll.

Accordingly, it is an object of the present invention to continuously introduce active materials onto or within each strand material, followed by separation of the system. As used herein, the term “strand” is considered to mean a narrow web having an active material strand that is narrower than the system strand.

This object is achieved according to the invention by the active material being applied by itself or in an appropriate manner to a thin stranded primary carrier having adhesiveness or other similar water solubility, depending on the chemical nature, optionally in solution form, similar to the introduction into the wick. do. This product is called active substance strands in the following.

One aspect of the invention is a) an active material strand, b) a large system strand that protrudes significantly beyond the active material strand on both sides, and c) a backing on one side unless the system strand acts as a backing layer. Layer, and d) a removable protective layer on the other side of the system.

Another aspect of the invention is that the active material is continuously introduced into or applied to a carrier to produce an active material strand, and the resulting strand is combined with a wider system strand that protrudes significantly beyond the active material strand on both sides, The system separates the removable protective layer on one side with the backing layer on the other side if the system strands do not act as a backing layer, and then combines the strands so that a large amount of active material cannot be released at the edge. A method of introducing an active substance into a system for use on the skin by incorporating the active substance into a carrier.

Thus, the protective layer is present in all cases regardless of whether the system strand acts as a backing layer.

The present invention is particularly active by incorporating the active material into the active material strands, adding the strands to the system strands and / or adding the system strands to the active material strands, and providing a final system having a separable protective layer and optionally a backing layer. A method of continuously introducing a material into a continuously produced thin system having a relatively large surface, such as a wafer or patch of active material, and a product produced by the method.

The active substance can be applied in or on the stranded carrier on its own or in the form of an active substance preparation, for example using dipping, printing or similar methods. It is also possible to prepare a mass incorporating the active material, extrude the mass and apply it directly to the system strand, perhaps under the formation of the active material strand, for example by spray coating or extrusion, or also to activate the extruded strand, yarn or fiber. Spin, squeeze, or bond together with material containing strands.

The solvent may also be cast onto system strands, cast as hot melts or cast into powder form as in coatings, dried to cool or energized to fix them in situ, cut into strand shapes. This can then be used "from the roll."

The active material strands may also be formed or composed of fibers, fabrics, nonwovens or suitable fabrics, or may be formed or composed of polymers to which the active material has been added. In this respect, suitable active material carriers are, for example, blocks based on conventional plastics such as polymers, copolymers and polyisobutylene (PIB), ethylenevinylacetate (EVA), polyacrylate or acrylate resins. Copolymers, silicones, styrene-isobutyl-styrene (SIS) block copolymers, and the like. Such dermal or transdermal systems are known to those skilled in the art. A) Martin C. Musolf: "Pressure-Sensitive Adhesives:" Science and Engineering "in Transdermal Controlled Systemic Medications, ed. By YW 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 oral systems such as wafers, for example, hydroxypropylcellulose, methylcellulose, starch or modified starch may be used.

According to a preferred embodiment, the activator carrier is applied to the strands, onto the system strands in a continuous process, and cut into specific dimensions by separation and / or punching in one operation to form each system. Here, a number of possibilities are considered:

1. A "system strand" usually consists of one or more plastic and / or aluminum films / sheets or foils, possibly stacked together. By adding the active strand to the film or foil and laminating it with the system strand, the active strand can be inserted between the film / sheet or foil.

2. The active strand can be applied onto the system strand “from the roll”.

3. At the same time, the active strand is added to the system strand which acts as the backing layer of the system.

4. Apply to an adhesive layer located on a protective sheet or foil.

5. Coat the active material strand, the front surface on the entire active material strand and / or part or all of the patch web with an adhesive hot melt adhesive coating or solvent-containing adhesive coating material, possibly at standard temperature.

6. Spray coat or extrude the active strand directly onto the system strand.

7. The backing layer-carrier layer is formed by one of these coatings with the required properties such as impermeability and strength to the active material.

8. Braid the appropriate strand thread.

9. Insert various, possibly multiple active strands, into the system strands. In this way, the active substance can be distributed very uniformly on the system strands without disturbing the production rate. This is a preferred embodiment in which a pattern is formed, as in fabrics, since the active strands are arranged parallel to the system strands and / or in a loop shape, according to a particularly useful embodiment. This also improves distribution uniformity.

10. Otherwise, combine strands with different active substances that are immiscible with one another or require special measurements for their binding, for example, to the liquid of the matrix or membrane system together with the active substances contained in the active substance strands. The contained actives are bound at the same or different concentrations to form binding systems, for example binding systems such as physostigmine and scopolamine, estrogen and gestagen. This is also a preferred embodiment.

11. According to another preferred embodiment, the active system strands are combined with different conventional systems such as allover matrices or membranes, so that different systems, eg concentration and release mechanisms, are simple to enhance the controlled release rate. Method can be formed on the surface or layer of the system, so that, for example, highly concentrated strands can be arranged in layers further away from the skin and low concentration strands can be arranged in layers close to the skin (or vice versa). Low initially, high release later (or vice versa).

12. According to another embodiment, the photosensitive and / or toxic or volatile active material may be processed to completely or partially encapsulate the active strand. Such capsule materials are of course permeable to the active material on at least one side, and the active material strands must be occluded immediately after application, for example by applying an additional layer with a laminate.

13. The thermal sensitivity of the active material contained in the active material strands during processing with the hot melt adhesive or the sensitivity occurring during the drying process can be considered by adding the active material to the strands on the side opposite the hot melt adhesive. In this case, the rear layer of the active material strand has a temperature insulating effect.

14. In some cases, upon separation of the system, simultaneous or additional pressure may be exerted in the form of embossing in which the edge is sealed such that a large amount of active material is not released from the edge. In conventional systems, it is often required to prevent high concentrations of active material from occurring at the edges. However, when the system of the present invention is used, transverse diffusion is poor anyway, and therefore no preventive measurement method is actually necessary at this point. In this respect, the present invention solves the drawbacks.

15. In another preferred embodiment, the active material strands can also be applied on corresponding system strands (carriers, intermediate layers or adhesive layers) continuously in the form of scrim nets, loop fabrics and the like. The second active substance can be treated to be integrated in the same way, for example by the following 16.

16. Add at least two different scrim nets containing the active material to the system strand or the corresponding carrier or adhesive layer.

A wide variety of active materials are suitable for the present invention, and particularly active materials that can be used transdermally are contemplated.

Nicotine

Corticosteroids: hydrocortisone, prednisolone, beclomethasone propionate, flumethasone, triamcinolone, triamcinolone acetonide, flucinolone, fluorinoline acetonide, fluorocinolone acetonide acetate, clobetasol propionate Etc.

Analgesics, anti-inflammatory agents: acetaminophen, mefenamino acid, flufenamino acid, diclofenac, diclofenic sodium alclofenac, oxyphenbutazone, phenylbutazone, ibuprofen, fluorobipropene, salicylic acid, 1-menthol, camphor, suline Dactolmethinesodium, naproxen, fenbufen etc.

Hypnotic active agents: phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazepam, lorazepam, haloperidol and the like.

Opiates such as diamorphine, morphine base, morphine hydrochloride, dihydrocodeine, buprenorphine, fentanyl and the like.

Mental stabilizers: flufenazine, thiolidazine, lorazepam, flunitrazepam, chloropromazine and the like.

Antihypertinsives: pindolol, indenolol, nifedipine, ropecidine, nipradinol, bucumolol, clonidine, bopindolol, bufranolol and the like.

Tubular actives such as ISDN, nitroglycerin and compounds thereof.

Antihypertensive active diuretics: hydrothiazide, bendroflumetiazide, cyclopentthiazide and the like.

Antibiotics: penicillin, tetracycline, oxytetracycline, pradiomycin sulfate, erythromycin, chloramphenicol and the like.

Anesthetics: lidocaine, benzocaine, ethylaminobenzoate and the like.

Fungicides: benzalkonium chloride, nitrofurazone, nistatin, acetosulfamine, clotrimazole and the like.

Antifungal agents: pentamycin, amphotericin B, pyrronitrin, clotrimazole and the like.

Vitamins: vitamin A, ergocalciferol, chlorecalciferol, octothiamine, riboflavin butyrate and the like.

Antiepileptics: nitrazepam, meprobamate, clonazepam and the like.

Coronary vasodilators: dipyridamole, erythrit tetranitrate, pentaerythrite tetranitrate, propatiltitrate and the like.

Antihistamines: diphenylhydramine-hydrochloride, chlorpheniramine, diphenylimidazole and the like.

Antitussives: dertromethorphan (hydrobromide), terbutalin (sulfate), ephedrine (hydrochloride), salbutanol (sulfate), isoproterenol (sulfate, hydrochloride) and the like.

Sex hormones: progesterone, estradiol, testosterone, etc.

Thymoleptics: doxepin, etc.

Additional therapeutic agents: 5-fluorouracil I, desmopressin, domperdon, scopolamine (hydrobromide), physostigmine, naltrexone, naloxone, peptides and the like.

Not surprisingly, this list is not comprehensive.

The products of the invention are suitable for the skin, but in particular in all forms for transdermal to the epidermis or mucosa. The term includes use as sanitary wafers, ie oral sanitary wafers. There are flatbed systems that improve oral hygiene by cleaning the actives or combinations of actives and / or reducing or blocking odors thereof. Thus, such oral hygiene wafers can be used orally and completely dissolved in the mouth, but they are not hard for oral use but are very flexible and orally administered with products whose ingredients are selected to be completely dissolved and physiologically degraded in body fluids. can do. Oral wafers of this type may also contain a pharmaceutically active substance instead of a hygienic active substance.

The method of the invention and the product thus obtained confer a number of advantages. Thus, the production speed of the system can be increased because no vertical movement with respect to the production cycle, guidance of the system, is necessary. As in the continuous process, the necessary separation can be made by rotating the cutting rolls, possibly forming embossing at the edges. In addition, special advantages are the scrap prevention and improved quality due to the absolute uniformity of the distribution of the active substance of the strands, which strands can be checked before production commences. Alternatively, the dosing problem that occurs during the manufacturing process is that once the strand is manufactured in a geometrically defined manner, the final dosing is given the limited width of the "patch web", ie the system strand, the length of the strand of the patch (volume, respectively, volume). , Length, area and thickness), ie preferably only by the length of the patch. If hot melt adhesive coatings are used, this method is particularly advantageous because the temperature at the moment the coating is applied is significantly lower than the temperature already present in mass production, and will have less interference with the active material of the strands.

The present invention also contains conventional (including flat) active agents, since it is possible to compensate for the decrease in concentrations occurring on the outer surface by simply increasing the active substance concentration of the active substance strand inserted into the oral cavity, thereby compensating for the reduced release of the active substance. It is particularly advantageous for oral systems. This particularly applies to the use of different concentrations of active substance strands, possibly containing different active substances.

By using the most different kinds of active strands with respect to the concentration and / or type of active substance, "wick" material, one can influence the controlled release properties.

Claims (20)

a) an active material strand, b) a system strand that prominently protrudes beyond the active material strand on both sides, and c) a backing layer on one side, unless the system strand acts as a backing layer, and d) the other side of the system. An active material-containing device for skin, characterized in that it consists of a removable protective layer of injury. The device of claim 1, wherein the skin is closed at the edge by embossing. The device according to claim 1 or 2, wherein a film is formed between the active strand and the system strand and the removable protective layer to control the amount of active substance released. The device according to any one of claims 1 to 3, wherein the active substance is dissolved in the strand, or the active substance strand has a porous structure, and the active substance is stored in the hole. 5. The device as claimed in claim 1, wherein the system strands consist of one or more plastics and / or aluminum films / sheets or foils, possibly laminated to one another. 6. The device according to any one of claims 1 to 5, wherein the active substance strands are arranged parallel to the system strands at right angles, diagonally or looped. The device according to any one of claims 1 to 6, comprising a combination of two or more different active substances or strands having active substance concentrations. 8. Device according to any one of the preceding claims, comprising an active substance strand having a different conventional system. Device according to any one of the preceding claims, characterized in that it is present in the form of a large area thin system, preferably in the form of a transdermal wafer or active material patch. 10. The device of claim 1, wherein the active strand is present in a form that is fully or partially encapsulated by the membrane. The active material is continuously introduced into or applied to the carrier to produce an active material strand, and the resulting strand is combined with a wider system strand that protrudes significantly beyond the active material strand on both sides, which system is on one side. A protective layer, which is characterized in that if the system strands do not act as a backing layer, the backing layer is provided on the other side, and then the joined strands are separated such that a large amount of active material cannot be released at the edge. A method of introducing an active substance into a system for use in combination with a carrier for the skin. 12. The active material strand according to claim 11, wherein the active material strand is continuously applied from the roll onto the system strand, and the system strand is subsequently separated. How to introduce. 13. The method according to claim 11 or 12, wherein the active substance is introduced into a stranded carrier having an absorbent property, and the active substance is introduced into the system for use in the skin in combination with the carrier. 14. The active material according to any one of claims 11 to 13, wherein the active material is combined with the strand material by dipping or printing. How to introduce. 15. The active material according to any one of claims 11 to 14, wherein the active material strand is produced by extrusion of the active material containing mass, preferably extruded or spray coated onto the system strand. Incorporating the active material into the system for use in the skin. The active substance according to any one of claims 11 to 14, wherein the active substance strand is prepared using an active substance-containing powder, preferably applied onto the system strand, and solidified by energy supply. To incorporate an active agent into the system for use in the skin in combination with a carrier. 17. The method of any one of claims 11 to 16, wherein the joined strands separate to form a patch, incorporating the active material with the carrier to introduce the active material into the system for use on the skin. 18. The active material according to any one of claims 11 to 17, wherein the active material strand is applied to the film / sheet or foil, and the product thus obtained is sealed with a system strand between the film / sheet or foil. To incorporate an active agent into the system for use in the skin in combination with a carrier. 19. The active material of any of claims 11 to 18, wherein the active material strand has an adhesive coating or is processed in an encapsulated form. How to Introduce Active Substances. The active substance-containing mass is applied directly to the system strand under the formation of an active substance strand, and the product thus prepared is further processed according to the method of any one of claims 10 to 17. Variant of the method.