Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
  • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
  • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
  • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches

Definitions

• the present invention relates to a transdermal therapeutic system (abbreviated to “TTS”) comprising an active substance carrier layer with at least one active substance-containing polymer matrix applied to the active substance carrier layer, comprising at least one pressure sensitive adhesive and at least one pharmacologically active substance which can be absorbed via human or animal skin, and one with an active ingredient-free pressure sensitive adhesive largely fully coated adhesive carrier layer, which is glued directly onto the flat side of the active ingredient carrier layer facing away from the active ingredient-containing polymer matrix by means of the active ingredient-free pressure sensitive adhesive, the adhesive carrier layer projecting all around the edge of the active ingredient carrier layer.
• TTS transdermal therapeutic system
• the invention further relates to the use of this transdermal therapeutic system and a kit containing the ses.
• Transdermal therapeutic systems are flat, layer-by-layer pharmaceutical products in which one or more active substances with or without auxiliary substances (e.g. penetration accelerators) are embedded in a possibly adhesive polymer matrix.
• this polymer matrix is produced by coating a carrier film with the polymer composition containing the active ingredient and then providing it with a cover film which remains on the skin even during the application of the transdermal therapeutic system.
• the carrier film serves as a protective layer for the polymer matrix during the duration of the storage and, if appropriate, as an application aid for the later use of the transdermal therapeutic system.
• Transdermal therapeutic systems enable continuous drug delivery over the entire application period. They are therefore comparable in terms of their concentration-time profiles to continuous drip infusions. Numerous transdermal therapeutic systems with different active substances and combinations of active substances are on the pharmaceutical market today.
• hormone replacement therapy particularly in menopausal women.
• estrogen-containing monopreparations were primarily used for this.
• transdermal therapeutic systems have been offered which contain a combination of estrogens (eg 17ß-estradiol) and gestagens (eg Norethiste ron).
• Testosterone the male sex hormone, also belongs to the group of steroid hormones that are used in hormone replacement therapy, especially in the treatment of hypogonadism.
• transdermal therapeutic systems are constructed as so-called matrix systems. These are systems in which the pressure-sensitive or non-pressure-sensitive polymer matrix has the active substance dissolved or suspended Contains form.
• the polymer matrix mostly consists of pressure-sensitive adhesives based on polyacrylates.
• the active substance patches are frequently cut square, for example square, in order to minimize cutting losses. Since square plasters are easier to detach from the skin, the fastening plaster is glued over them for a better grip, which generally has rounded corners or is generally round.
• US 2017/0290779 A1 discloses a plaster for dermal use, the plaster comprising an active reservoir layer, a carrier layer projecting beyond this layer and a further carrier layer projecting from both previous layers, which is coated with an adhesive.
• the reservoir layer can comprise a pressure-sensitive adhesive and / or a non-adhesive polymer matrix. The production of this layer structure is extremely complex and requires a high degree of manufacturing precision in its composition.
• WO 2016/081616 A2 describes a plaster formulation for the transdermal delivery of water-soluble active ingredients, peptides, proteins and oligosaccharides.
• the patch comprises a layer which contains an active ingredient and a polymer matrix, and an adhesive layer, the adhesive layer projecting beyond the active ingredient / polymer layer. Furthermore, the adhesive layer comprises an adhesive-free zone, which projects above the active ingredient / polymer layer.
• EP 0 755 284 B1 teaches a topical dressing for dermal and / or transdermal administration of a substance, the dressing comprising a carrier layer which is coated with an adhesive. Furthermore, the backing layer comprises a circular, cut-out area that is adhesive-free. A cutout is defined in the cut-out area, into which a cushion containing an active ingredient is inserted, the cushion having a smaller diameter than the cut-out area. This creates a transition area of reduced layer thickness between the cushion containing the active ingredient and the adhesive layer.
• the object of the present invention was to provide a transdermal therapeutic system of the type mentioned at the outset, which can be manufactured more cost-effectively, at the same time has good adhesive properties on the skin and in which a migration of the pharmacologically active ingredient into the adhesive of the Fastening plasters largely prevented.
• this object is achieved in that a region of reduced coating thickness on the active substance-containing polymer matrix and / or on the active substance-free pressure sensitive adhesive is provided between the active substance-containing polymer matrix and the active substance-free pressure-sensitive adhesive layer and / or on the active substance-free pressure-sensitive adhesive which acts as a diffusion barrier Diffusion of the pharmacologically active substance and / or one or more auxiliary substances in the adhesive of the adhesive backing layer is prevented.
• the invention thus relates to a transdermal therapeutic system comprising
• an active substance carrier layer with at least one active substance-containing polymer matrix applied to the active substance carrier layer containing at least one pressure sensitive adhesive and at least one pharmacologically active substance which can be absorbed by human or animal skin, and
• the peripheral circumferential area of reduced coating thickness is preferably produced in the manner in which the active substance carrier layer, initially coated over its entire area with the active substance-containing polymer matrix, is fed to a punching tool which comprises a hollow cylinder and an outside of the hollow cylinder, in particular concentrically and directly adjacent to the cutting knife.
• a punching tool which comprises a hollow cylinder and an outside of the hollow cylinder, in particular concentrically and directly adjacent to the cutting knife.
• the hollow cylinder is first pressed onto the coated active substance carrier layer. This pushes the adhesive away to the side so that the Coating thickness of active ingredient-containing polymer matrix is significantly reduced in this area.
• the active ingredient carrier layer is then punched out with the cutting edge around the area of reduced coating thickness of the active ingredient-containing polymer matrix by means of the cutting knife.
• This procedure is particularly advantageous because in this process it is possible to start with a support material for the active ingredient support layer coated over the entire area with the active ingredient-containing polymer matrix and the coated active ingredient support layer can be produced in one operation without loss of material and without expensive local coating methods. Even if a residual layer thickness of the active substance-containing polymer matrix remains during this process, this is still sufficient to practically completely prevent diffusion of the pharmacologically active substance into the adhesive of the adhesive backing layer.
• the present invention thus also relates to a method for producing a transdermal therapeutic system according to the invention, comprising the steps
• an active substance carrier layer with at least one active substance-containing polymer matrix applied to the active substance carrier layer and containing at least one pressure sensitive adhesive and at least one pharmacologically active substance that is absorbable via human or deep skin, as well as
• the cutting knife is preferably first placed in its starting position and only then is the hollow cylinder raised.
• the punching is preferably carried out by the flat side facing away from the active ingredient-containing polymer matrix, but it is also possible to punch from the side of the active ingredient-containing polymer matrix.
• the diecut obtained as above, with its flat side facing away from the active ingredient-containing polymer matrix, is glued onto the adhesive side of the adhesive backing layer in such a way that the adhesive backing layer extends beyond the edge of the active ingredient carrier layer.
• the transdermal therapeutic system thus produced is then typically covered and packaged with a protective layer in the form of a release liner on the adhesive side.
• the invention further relates to the use of a transdermal therapeutic system according to the invention for the treatment of hypogonadism, for hormone replacement therapy, Alzheimer's, Parkinson's, multiple sclerosis, bipolar disorders, muscle tension, severe pain, high blood pressure or for contraception just to name a few.
• Another object of the present invention relates to a kit comprising a transdermal therapeutic system according to the invention in an outer packaging and optionally a usage instruction comprising an instruction for use according to the invention.
• pressure sensitive adhesive systems known to the person skilled in the art can be used independently of one another, which are suitable for use on the skin.
• a pressure-sensitive adhesive in the sense of the present invention is an adhesive which has a permanent tack in a range from 0 to 40 ° C., in particular at room temperature, and forms good adhesion to various surfaces under slight pressure, in particular to human skin. This is also known as "tacky".
• Suitable adhesives are known to the person skilled in the art from the technical field of adhesive tapes, in particular medical adhesive tapes or rapid wound dressings.
• Suitable pressure sensitive adhesives have, for example, a glass transition temperature T g of ⁇ -10 ° C.
• the glass transition temperature T g can be determined by means of DSC (differential scanning calorimetry) with a Mettler DSC 12E (Mettler Toledo GmbH, Giessen, DE) at a heating rate of 10 K / min.
• Examples of pressure-sensitive adhesives that can be used are those as disclosed in DE 101 41 652 A1. Pressure sensitive adhesives that are suitable on the market are available, for example, under the brand names DUROTAK® and GELVA® (both from Henkel AG & Co. KGaA).
• Suitable silicone adhesive (BIO-PSA 7-4101, BIO-PSA 7-4102, BIO-PSA 7-4201, BIO-PSA 7-4202, BIO-PSA 7-4301, BIO-PSA 7-4302, BIO-PSA 7- 4401, BIO-PSA 7-4402, BIO-PSA 7-4501, BIO-PSA 7-4502, BIO-PSA 7- 4601, BIO-PSA 7-4602,), silicone-acrylate hybrid systems (7-6101 SilAc Hybrid PSA, 7-6102 SilAc Hybrid PSA, 7-6301 SilAc Hybrid PSA, 7-6302 SilAc Hybrid PSA) and 2-component silicone adhesive (MG7-9700 Kit (A&B), MG7-9800 Kit (A&B), MG7-9850 Kit (A&B), MG7- 9900 Kit (A&B), MG7-1010 Kit (A&B)) are from Dow Corning, Polyisobutylene (Oppanol B10 N, Oppanol B10 SFN, Oppano
• the transdermal therapeutic system comprises an active substance carrier layer and an adhesive carrier layer.
• the carrier material used for the active substance carrier layer and the adhesive carrier layer can be the same or different.
• the carrier can be in the form of a film, fabric, scrim, fleece or knitted fabric.
• the carrier is expediently so flexible that the system can adapt to the skin.
• Suitable backing materials include conventional flexible backing materials used for pressure sensitive adhesive tapes, such as polyethylene, in particular low-density polyethylene, linear low-density polyethylene, metallocene polyethylene, high-density polyethylene, polypropylene, polyesters such as polyethylene terephthalate, randomly oriented nylon fibers, ethylene vinyl acetate copolymer, Polyurethane, natural fibers such as rayon and the like. Supports that are layered, such as polyethylene terephthalate-aluminum-polyethylene composites, are also suitable.
• the carrier should be essentially inert to the components of the active substance-containing polymer matrix and the active substance-free pressure sensitive adhesive.
• the thickness of the carrier material depends on the desired requirements and is, for example, in the range from 5 to 100 ⁇ m.
• a polyethylene terephthalate film is preferably used as the carrier material, the thickness of which is more preferably in the range from 10 to 40 ⁇ m.
• the non-coated side of the active ingredient carrier layer and in particular the adhesive carrier layer can be lacquered, for example in skin colors, in order to make the patch less visually conspicuous when worn.
• the area of the transdermal therapeutic system depends on the requirements and is typically 1.0 to 250 cm 2 .
• the polymer matrix of the active substance-containing polymer matrix and the active substance-free pressure sensitive adhesive can be provided with a protective layer covering the entire surface, the protective layer on the Flat side facing the active substance-containing polymer matrix is in particular equipped with an adhesion-reducing coating, preferably with siliconization or, in particular in the case of silicone adhesives, with fluorosiliconization.
• the adhesion-reducing coating enables the protective layer to be removed more easily, since this is peeled off before the TTS is used to expose the tacky areas.
• Suitable protective layers include conventional release liners comprising a known sheet material, such as a polyester sheet, a polyethylene sheet, a polystyrene sheet, or a paper coated with polyethylene coated with a suitable fluoropolymer or silicone based coating.
• the invention relates to a transdermal therapeutic system comprising
• an active substance carrier layer with at least one active substance-containing polymer matrix applied to the active substance carrier layer containing at least one pressure sensitive adhesive and at least one pharmacologically active substance which can be absorbed by human or animal skin, and
• the invention relates to a system according to embodiment 1, characterized in that the pressure-sensitive adhesive layer is largely coated with the active substance-free pressure-sensitive adhesive and glued to the active substance carrier layer, the active substance carrier layer having the area of reduced coating thickness on the active substance-containing polymer matrix all around the edge.
• the invention relates to a system according to embodiment 2, characterized in that the peripheral area of reduced coating thickness is produced or can be produced by the material for the active substance carrier layer coated with the active substance-containing polymer matrix being fed to a punching tool which has a hollow cylinder and a outside of the hollow cylinder, in particular concentrically and directly comprises a cutting knife arranged adjacent to it, the hollow cylinder first being pressed onto the coated active substance carrier layer while reducing the coating thickness of the polymer matrix containing the active substance, and then the cutting agent knife is used to punch out the active substance carrier layer with a circumferential area of reduced coating thickness of the active substance-containing polymer matrix by means of the cutting knife.
• a punching tool which has a hollow cylinder and a outside of the hollow cylinder, in particular concentrically and directly comprises a cutting knife arranged adjacent to it, the hollow cylinder first being pressed onto the coated active substance carrier layer while reducing the coating thickness of the polymer matrix containing the active substance, and then the cutting agent knife is used to punch out the active substance
• the invention relates to a system according to embodiment 1, characterized in that the adhesive carrier layer on the border to the active substance carrier layer continuously has the area of reduced coating thickness on the active substance-free pressure sensitive adhesive.
• the invention relates to a system according to one of the preceding embodiments, characterized in that in the system the active substance-containing polymer matrix is applied directly to the active substance carrier layer and the active substance-free pressure-sensitive adhesive is applied directly to the adhesive carrier layer and between the flat side facing away from the active substance-containing polymer matrix Active ingredient carrier layer and the active ingredient-free pressure sensitive adhesive of the adhesive carrier layer is no further layer.
• the invention relates to a system according to one of the above embodiments, characterized in that the polymer matrix of the active ingredient-containing polymer matrix and the active ingredient-free pressure sensitive adhesive is selected independently of one another from acrylates, silicone pressure sensitive adhesives, polyisobutylenes, SIS copolymers, silicone acrylate Hybrid systems, such as those sold by Dow Corning Healthcare Solutions, and mixtures thereof.
• the invention relates to a system according to one of the above embodiments.
• the pharmacologically active substance is selected from the group of the ⁇ -adrenoreceptor agonists, the ⁇ -adrenoreceptor agonists, the a Adrenoreceptor blockers, the ⁇ -adrenoreceptor blockers, the analgesics (narcotics), the analgesics (non-narcotics), the androgens, the anesthetics, the antiallergics, the antiandrogens, the antianginaosa, the antiarrhythmics, the penicilli ne, the anti-diabetic, the anti-dementia, the anti-histamines, the anti-migraine agents, the hydrogenated ergot alkaloids, the Ca-antagonists, the hormones, the serotonin antagonists, the thrombocyte aggregati, the adrenoreceptor agonists, the a
• the invention relates to a system according to one of the preceding embodiments, characterized in that the circumferential area of reduced coating thickness is at most 20% of the thickness of the polymer matrix of the active substance-containing polymer matrix and / or the active ingredient-free pressure sensitive adhesive, in particular at most 15%, preferably 0.1 to 12%. In the area of reduced coating thickness, the active substance-containing polymer matrix and / or the active substance-free pressure sensitive adhesive can also be completely removed.
• the invention relates to a system according to one of the above embodiments, characterized in that the circumferential area of reduced coating thickness has a width of 0.05 to 5.0 mm, in particular 0.1 to 3.0 mm.
• the invention relates to a system according to one of the above embodiments, characterized in that the circumferential area of reduced coating thickness is essentially not interrupted.
• the invention relates to a system according to one of the preceding embodiments, characterized in that the coating thickness of the active ingredient-containing polymer matrix and / or of the active ingredient-free pressure sensitive adhesive is 20 to 800 pm, in particular 40 to 400 pm.
• the invention relates to a system according to one of the preceding embodiments, characterized in that a protective layer covering the entire surface of the polymer matrix of the active substance-containing polymer matrix and the active substance-free pressure-sensitive adhesive is provided, the protective layer on the flat side facing the active substance-containing polymer matrix in particular with is equipped with an adhesion-reducing coating, preferably with siliconization or fluorosiliconization.
• the invention relates to a method for producing a transdermal therapeutic system according to one of the embodiments 1 to 12, comprising the steps
• an active ingredient carrier layer with at least one active ingredient-containing polymer matrix applied to the active ingredient carrier layer, comprising at least one pressure sensitive adhesive and at least one pharmacologically active ingredient, which can be absorbed via human or animal skin, and
• the adhesive carrier layer extends all around the edge of the active substance carrier layer, characterized in that between the active substance-containing polymer matrix and the active substance-free pressure-sensitive adhesive there is a coating thickness of active substance-containing polymer matrix and / or on the active substance-free pressure-sensitive adhesive which is reduced by a continuous area, the edge-circumferential area of reduced coating thickness preferably being produced by coating the entire area with the active substance-containing polymer matrix
• a punching tool which comprises a hollow cylinder and an outside of the hollow cylinder and in particular concentrically and immediately adjacent to the cutting knife arranged sem, wherein the hollow cylinder is first pressed onto the coated active substance carrier layer while reducing the coating thickness of the active substance-containing polymer matrix and then, by means of the cutting knife, the active ingredient carrier layer with a peripheral area of reduced coating thickness acting on substance-containing polymer matrix is punched out.
• the invention relates to the use of a transdermal therapeutic system according to one of the embodiments 1 to 12 for the treatment of the human or animal body, in particular hypogonadism, for hormone substitution therapy, for Alzheimer's, for Parkinson's, for multiple sclerosis, for bipolar Disorders, muscle tension, severe pain, high blood pressure or for contraception.
• the invention relates to a kit comprising at least one transdermal therapeutic system according to one of embodiments 1 to 12 in an outer packaging, and optionally to a user manual comprising an instruction for use according to embodiment 14.
• Fig. 1 shows an intermediate stage in the manufacture of a transdermal therapeutic system according to the invention
• FIG. 2 shows an embodiment of the completed transdermal therapeutic system according to the invention according to FIG. 2.
• the transdermal therapeutic system 1 comprises an active substance carrier layer 2 with at least one active substance-containing polymer matrix 3 applied to the active substance carrier layer 2, containing at least one pressure sensitive adhesive and at least one pharmacologically active substance, in the present case scopalamine, which can be absorbed via human or animal skin.
• the active substance carrier layer 2 has an area around the edge of a reduced coating thickness 4 of the active substance-containing polymer matrix and is applied to a protective layer 5 which covers the active substance-containing polymer matrix 3 over its entire area and projects beyond the edge and is provided with a silicone coating to reduce the adhesion of the pressure-sensitive adhesive.
• the active substance carrier layer 2 On the flat side opposite the active substance-containing polymer matrix 3, the active substance carrier layer 2 is covered over the entire surface with an adhesive carrier layer 6, which is glued directly onto the active substance carrier layer 2 by means of an active substance-free pressure sensitive adhesive 7.
• the adhesive backing layer 6 is coated over the entire area with the active ingredient-free pressure sensitive adhesive 7.
• an active substance carrier layer 2 with an active substance-containing polymer matrix 3 is firstly comprised of at least one pressure-sensitive adhesive, in the present case a silicone-based pressure-sensitive adhesive, and at least one pharmacologically active substance, which is absorbable via human or animal skin Scopalamin, is coated.
• the material for the active substance carrier layer 2, which is initially coated over the entire surface with the active substance-containing polymer matrix 3, is fed to a punching tool which comprises a hollow cylinder and an outside of the hollow cylinder and a cutting knife arranged concentrically and immediately adjacent to the latter.
• the hollow cylinder is pressed onto the coated active substance carrier layer 2 while reducing the coating thickness of the active substance-containing polymer matrix, whereby a circumferential area of reduced coating thickness 4 of the active substance-containing polymer matrix is obtained.
• the active ingredient carrier layer 2 is punched out outside the circumferential area of reduced coating thickness 4 by means of the cutting knife and applied to a protective layer 5 provided with a silicone coating, which completely covers the active ingredient-containing polymer matrix 3 and projects beyond it on the edge.
• the active substance-containing polymer matrix 3 depending on the contact pressure of the hollow cylinder and the softness of the active substance-containing polymer matrix 3, can be removed completely or largely completely in the region of the hollow cylinder.
• An intermediate product 10 is obtained, the layer structure of which is shown in FIG. 1.
• the active substance carrier layer 2 is covered over the entire surface on the flat side opposite the active substance-containing polymer matrix 3 with an adhesive carrier layer 6, which is glued directly onto the active substance carrier layer 2 by means of an active substance-free pressure-sensitive adhesive 7, whereby the transdermal therapeutic system 1 according to the invention is obtained.
• an adhesive carrier layer 6 which is glued directly onto the active substance carrier layer 2 by means of an active substance-free pressure-sensitive adhesive 7, whereby the transdermal therapeutic system 1 according to the invention is obtained.
• a silicone-based pressure sensitive adhesive is used.
• the transdermal therapeutic system 1 produced in this way is individually sealed airtight after production in an aluminum-laminated polyester film packaging and stored for 6 months at 40 ° C. and 75% rel. Humidity subjected in a climatic chamber. The transdermal therapeutic system 1 is then removed from the packaging and examined for a possible migration of the scopolamine. No scopalamine could be detected in the drug-free pressure-sensitive adhesive 7.
• the protective layer 5 is removed and the remaining layer structure is placed on the adhesive side of the desired area of skin and pressed on.

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• Health & Medical Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Dermatology (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 2018
  • 2018-11-30 DE DE102018130469.2A patent/DE102018130469A1/de active Pending
• 2019
  • 2019-11-25 JP JP2021530909A patent/JP2022510279A/ja active Pending
  • 2019-11-25 CA CA3121252A patent/CA3121252A1/en active Pending
  • 2019-11-25 CN CN201980078931.4A patent/CN113194933A/zh active Pending
  • 2019-11-25 US US17/298,551 patent/US20220079887A1/en active Pending
  • 2019-11-25 EP EP19809785.9A patent/EP3886821A1/de active Pending
  • 2019-11-25 WO PCT/EP2019/082448 patent/WO2020109241A1/de unknown
  • 2019-11-25 BR BR112021009956-5A patent/BR112021009956A2/pt unknown

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