EP3952818A1 - Matériau dentaire de reminéralisation - Google Patents

Matériau dentaire de reminéralisation

Info

Publication number
EP3952818A1
EP3952818A1 EP20720901.6A EP20720901A EP3952818A1 EP 3952818 A1 EP3952818 A1 EP 3952818A1 EP 20720901 A EP20720901 A EP 20720901A EP 3952818 A1 EP3952818 A1 EP 3952818A1
Authority
EP
European Patent Office
Prior art keywords
ions
dental material
coacervate
material according
partner
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP20720901.6A
Other languages
German (de)
English (en)
Inventor
Dominik GRUBER
Stephan Neffgen
Olav-Sven BECKER
Holger Müller
Helmut Cölfen
Elena Sturm
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Muehlbauer Technology GmbH
Original Assignee
Muehlbauer Technology GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Muehlbauer Technology GmbH filed Critical Muehlbauer Technology GmbH
Publication of EP3952818A1 publication Critical patent/EP3952818A1/fr
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/20—Protective coatings for natural or artificial teeth, e.g. sealings, dye coatings or varnish
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/60—Preparations for dentistry comprising organic or organo-metallic additives
    • A61K6/69—Medicaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/70—Preparations for dentistry comprising inorganic additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/042—Gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/20—Halogens; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/24—Phosphorous; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/817—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions or derivatives of such polymers, e.g. vinylimidazol, vinylcaprolactame, allylamines (Polyquaternium 6)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/88—Two- or multipart kits
    • A61K2800/882—Mixing prior to application
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/88—Two- or multipart kits
    • A61K2800/884—Sequential application

Definitions

  • the invention relates to a remineralizing dental material, each with at least one cation and one anion, which are freshlybil det as part nerionen to form a remineralization substance.
  • the invention also relates to the use of this dental material, a method for its application and a kit for its production.
  • Dental materials for all types of conservative treatment of tooth hard substance defects are known.
  • a mineralizing effect of such materials is intended to stabilize the natural hard tooth substance remaining, for example after an invasive treatment, against further, for example, bacterial-induced degradation.
  • Mineralization can be induced by the release of certain ions such as Ca2 + or F ⁇ from the material with the access of suitable counterions from the saliva on or in the hard tooth tissue.
  • a new, poorly soluble inorganic solid is then formed, which replaces lost mineral in the hard tooth substance (mineral substitute).
  • so-called bioactive glasses are used here.
  • WO2017 / 161179A1 discloses a remineralizing agent which contains a 60:40 mixture of Bioglass 45S5 and polyaspartic acid. It only provides a low concentration of releasable ions. In addition, the selection and combination options of releasable ions and thus the type of remineralization are limited.
  • US2010 / 0272764A1 discloses a polymerizable dental resin composite with remineralizing properties. This ent holds microcapsules each containing a calcium nitrate solution, a potassium hydrogen phosphate solution and a sodium fluoride solution. The ions are released through the semipermeable membrane of the capsules over a concentration gradient. It should be possible to manufacture the microcapsules by complex coacervation of oppositely charged polyelectrolytes. The low concentration of releasable ions is also a disadvantage here.
  • the invention is based on the object of creating a dental material of the type mentioned at the outset that enables effective re-mineralization.
  • the invention proposes that at least one of the partner ions is polyvalent and is contained as a Ge genion in a coacervate.
  • the invention relates to a remineralizing dental material.
  • Remineralization and demineralization are biological processes that take place alternately in the area of the interface between the tooth and the oral cavity and in which mineral ions are either released or reinstalled via the saliva.
  • demineralization the usually acid-induced (e.g. due to cariogenic plaque) mineral loss of the tooth due to the dissolution of the inorganic, especially Hydroxyapatite-containing components of the tooth, which is a primary process in the formation of caries (P. Shellis in: Caries,
  • Remineralization in the narrower sense is the deposition or deposition of mineral-like material, especially mounted on an apatite base in the area of the tooth surface (P. Shellis ibid., p. 23,
  • remineralization is understood to mean any process in which inorganic material is deposited on the existing hard tooth substance that has potentially been damaged by demineralization by precipitation processes.
  • the precipitation can cause the growth of existing apatite crystals of the tooth substance or lead to the formation of new inorganic material at the site of remineralization.
  • Suitable inorganic materials can be materials derived from apatite or other poorly soluble, biocompatible compounds. They are referred to according to the invention as remineralization substances.
  • Tooth substance is understood to mean any mineralized tooth substance, in particular tooth enamel, dentin and tooth cement.
  • Partner ions are cations and anions that can jointly form a re-mineralization substance.
  • Coacervation is a liquid-liquid phase separation.
  • An ionic polymer or macroion for example an ionic poly phosphate
  • a polyvalent counterion for example calcium
  • Coacervates are polyelectrolytes crosslinked via polyvalent counterions. Coacervates are present as a highly viscous phase in an aqueous medium. Depending on the level of the molecular weights of the underlying polyelectrolytes, the coacervates are as liquid, viscous to visco-plastic substances, which are present in separate phases in the aqueous medium. Coacervates only exist in a certain range of the molar ratio between polyelectrolyte and polyvalent counterion and from a minimum concentration of the polyelectrolyte. If the counterion content is too low or the concentration of the coacervate formers (polyvalent counterion and polyelectrolyte) is too low, phase separation does not occur in water.
  • Suitable coacervates are formed from anionic or cationic polyelectrolytes and polyvalent cations or polyvalent anions. Suitable coacervates contain ionic polyelectrolyte and polyvalent counterions which crosslink it.
  • the coacervates are preferably produced by mixing the aqueous solutions of anionic or cationic polyelectrolytes and of polyvalent cations or anions.
  • anionic polyelectrolytes and polyvalent Katio NEN mixed and mixed cationic polyelectrolytes and polyvalent anions.
  • the coacervates form a separate liquid, more viscous phase in the mixture.
  • the coacervates are preferably separated off. This is done in each case by suitable known procedures such as decanting or centrifuging.
  • the isolated Coa cervates are preferably cleaned. This is preferably done by simply washing with a solvent, preferably with water.
  • the invention has recognized that partner ions of a remineralization material with a high mineralization potential for hard tooth substance can be made available in a dental material if at least one of these partner ions is used as Counterion is present in a coacervate.
  • a mineralizing effect is intended to stabilize the natural hard tooth substance, for example after an invasive treatment, against further, for example, bacterial-induced degradation.
  • Mineralization can be induced by the release of certain ions such as Ca 2+ or F ⁇ from the material with the access of suitable partner ions from the saliva on or in the hard tooth tissue. New, poorly soluble inorganic solid is then formed, which replaces the lost mineral in the hard tooth substance (mineral substitute).
  • the mineralization potential of known dental materials is limited.
  • this is due to the fact that the known components with a mineralizing effect can only be added to a dental material in limited amounts without deteriorating its other material properties.
  • this is due to the limited speed and quantity at which the ions can be released into the corresponding dental material or from the dental material, for example with known glass ionomer cements.
  • Dental materials according to the invention with a mineralizing effect are advantageously present when used in a liquid or pasty, but at least in an adaptable form, and are applied in this form to the hard tooth substance to be treated. There they are manually applied to the surface and potentially shaped. Since remineralization processes are generally rather slow, the material should remain in place for at least a certain period of time after it has hardened. In an application that is particularly suitable for long-term treatment successes, it solidifies after a certain time, whereby the processing time must be sufficient for manual processing. The hardened form of the material then also serves to protect the site of remineralization from mechanical and / or chemical degradation. Before and, if provided, after hardening, the materials should be able to supply ions for mineralizing the hard tooth substance with the formation of mineral substitutes.
  • the dental materials with mineralization potential should be used sensibly for stabilizing tooth enamel.
  • This can be tooth enamel partially degraded by carious processes, tooth enamel in the area affected by invasive dental treatments or areas undermined by malformations in the tooth enamel (eg MIH).
  • a desirable dental material mineralizes the under-mineralized hard tooth substance in contact and covers such areas at least for a period of time that is necessary for the mineralization of the tooth enamel areas. Permanent retention in the sense of a filling material is also conceivable.
  • the application leads to a stabilization of the tooth substance, which includes the remineralization and the physical protection over the period of time necessary for the remineralization. Ideally, in such an application, the corresponding material also adheres to the area to be treated.
  • a further preferred application of such materials is directed towards the use as underfilling material, especially when deep cavities are present and, under certain circumstances, demineralized dentine remains in the cavity.
  • stabilizing effects and permanent protection are the goal.
  • a problem with the materials in the prior art is that fillings based on inorganic materials are not always sufficiently chemically stable and / or do not or only insufficiently adhere to the substrate.
  • a preferred requirement of the mineral substitute formed is that it is at least as chemically stable to an acidic aqueous environment as the hard tooth substance (hydroxylapatite); it is particularly preferably more stable. Stability against an acidic aqueous environment means the resistance to dissolution in such a medium.
  • the formation of such chemically stable mineral substitutes prevents the material from dissolving under, for example, microbiological action and the formation of acid.
  • one of the partner ions is polyvalent and is contained as a counterion in a coacervate, and that a second partner ion is contained in aqueous solution.
  • a second polyelectrolyte which is charged differently than the polyelectrolyte of the coacervate can preferably also be contained. If the polyelectrolyte of the coacervate is thus a cationic polyelectrolyte, this second polyelectrolyte is an anionic polyelectrolyte and vice versa. It has been shown that the addition of such a second polyelectrolyte leads to additional deep mineralization taking place in the tooth substance (in particular dentin). In particular with demineralized dentine, this has the advantage that the mineralization potential can be improved via the penetration depth of a partner contained in the coacervate, so that improved remineralization can take place deep into the dentine.
  • both partner ions can be polyvalent and each contain a coacervate as counterion. More preferably one of the partner ions is bivalent, i.e. the charge is 2. Preferred charge numbers are +3, +2, -2 and -3.
  • coacervates can also contain monovalent cations / anions. It can be preferred that portions of the polyvalent or monovalent cations have antimicrobial properties. Suitable cations with these properties are, for example, silver or copper ions. It can be preferred that portions of the more or monovalent anions have biological or remineralization supporting effects. It is particularly preferred that fluoride is contained as the monovalent anion.
  • the anionic polyelectrolytes for forming the coacervates with polyvalent cations can preferably be selected from the group of organic polyelectrolytes, preferably consisting out
  • Polymers and copolymers which have carboxylic acid groups, phosphoric acid groups, phosphonic acid groups and / or sulfonic acid groups and their salts and their partial esters; before given to polycarboxylic acids, polyalkylenephosphoric acids, polyalkylenephosphonic acids, for example polyvinylphosphonic acid and polysulfonic acids and their salts and their partial esters; more preferably poly (meth) acrylic acid, polyaspartic acid, polyitaconic acid and polyglutamic acid and their salts; acidic proteins, acidic protein derivatives and their salts, preferably of lysosymes or gelatin (type B); acidic polysaccharides and their salts, preferably carregen, pectin, alginic acid and hyaluronic acid.
  • the anionic polyelectrolytes for forming the coacervates with polyvalent cations preferably have average molecular weights (weight average Mw) between 3 kDa and 1500 kDa, more preferably between 5 and 500 kDa, more preferably between 8 kDa and 200 kDa, more preferably between 8 and 50 kDa.
  • the polyvalent cations are preferably selected from the group consisting of mineral-forming cations; preferably metal cations; more preferably the metals of groups 2A, 3B, 3A of the PSE and the lanthanoids; more preferably Ba 2+ , Ca 2+ , Sr 2+ , Tb 3+ and Yb 3+ ; more preferably Ca 2+ and / or mixtures of metal cations with Ca 2+ .
  • Coacervates with mixtures of cations e.g. B. by partial substitution of Ca 2+ by especially Sr 2+ in Ca-containing coacervates, are possible.
  • a coacervate based on polyacrylic acid and Ca 2+ ions at least a pH of 5 and a polyacrylic acid concentration of> 1 mg / ml, preferably> 10 mg / ml, are provided to form the desired isolable coacervate.
  • the cationic polyelectrolytes for forming the coacervates with polyvalent anions are preferably selected from organic polyelectrolytes, preferably from the group consisting of polymers and copolymers having primary, secondary and / or tertiary amino groups and their salts; preferably polyamines; more preferably polyallylamine, linear or branched polyethyleneimine, chitosan, polylysine and polyarginine and their salts; more preferably polyallyamine hydrochloride (PAH).
  • organic polyelectrolytes preferably from the group consisting of polymers and copolymers having primary, secondary and / or tertiary amino groups and their salts; preferably polyamines; more preferably polyallylamine, linear or branched polyethyleneimine, chitosan, polylysine and polyarginine and their salts; more preferably polyallyamine hydrochloride (PAH).
  • PHA polyallyamine hydrochloride
  • coacervate based on cationic polyelectrolytes can be the combination of polyallyamine hydrochloride (PAH) with phosphate or hydrogen phosphate as Ge genion.
  • PAH polyallyamine hydrochloride
  • the polyallyamine is present as protonated as possible and the phosphate ion is present as deprotonated as possible for the production of the coacervate.
  • the cationic polyelectrolytes for forming the coacervates with polyvalent anions preferably have average molecular weights (weight average Mw) between 3 kDa and 1500 KDa, preferably between 5 and 500 kDa, more preferably between 8 kDa and 200 kDa, more preferably between 8 and 50 kDa.
  • the polyvalent anions are preferably selected from the group consisting of mineral-forming anions, preferably orthophosphate ions, diphosphate ions, metaphosphate ions, silicates, in particular inorganic silicate ions, preferably ortho, ino and ribbon silicate ions, and partially organically modified silicate ions, in particular alkyloxy -Silicate ions, sulfate ions, tungstate ions, vanadate ions, molybdate ions and carbonate ions, more preferably orthophosphate ions, diphosphate ions, metaphosphate ions, sulfate ions, tungsten ions, vanate ions, molybdate ions, more preferably orthophosphate ions and / or mixtures of orthophosphate ions with mineral-forming anions.
  • mineral-forming anions preferably orthophosphate ions, diphosphate ions, metaphosphate ions, silicates, in particular inorganic silicate ions, preferably ortho, ino and ribbon silicate ions, and partially
  • the dental material according to the invention is preferably a liquid and / or an emulsion and / or a suspension, preferably with a dynamic viscosity greater than 50 mPas, preferably greater than 100 mPas.
  • the dental material according to the invention is preferably a solid, more preferably a powder.
  • the dental material according to the invention is preferably a gel or a paste.
  • the dental material can contain 1 to 100% by weight of partner ions and coacervate, preferred lower limits and upper limits are 5, 10, 15, 25, etc. to 95% by weight. According to the invention, the specified intervals of 5% by weight each can be combined as desired to form areas of lower limits and upper limits.
  • the dental material according to the invention preferably contains water, preferably between 5 and 95% by weight, preferred lower limits and upper limits are 5, 10, 15, 25, etc. to 95% by weight. According to the invention, the stated intervals of 5% by weight in each case can be combined as required to form ranges of lower limits and upper limits.
  • the coacervate can have a water content of 0.1 to 90% by weight, preferably 1 to 75% by weight, further preferably 5 to 60% by weight.
  • the coacervate can have a water content of 0.1 to 50% by weight, preferably 1 to 25% by weight, further preferably 5 to 25% by weight.
  • the concentration of the polyelectrolyte forming the coacervates and its counterions in the coacervate is between 10 and 100% by weight, preferred lower limits are 25 or 40, more preferably 45% by weight, preferred upper limits are 55 or 75, more preferably 85, 90 and 95% by weight.
  • fluoride ions are contained as the partner ion.
  • the partner ions are essentially soluble in the dental material (in particular before the formation of the remineralization substance).
  • the dental material according to the invention can be self-curing forms. According to the invention it is preferred that the dental material has a processing time and / or hardening time between 1 and 5 minutes according to ISO 9917: 2007.
  • the hardened dental material is self-adhesive, preferably has a shear bond strength of at least 3.5 MPa on tooth enamel and / or dentin.
  • the hardened dental material preferably has a compressive strength greater than 50, preferably greater than 100, more preferably greater than 200 MPa and a flexural strength greater than 20, preferably greater than 25 MPa according to ISO 9917: 2007.
  • the dental material according to the invention has a high mineralization potential for the hard tooth substance and, in a particularly preferred embodiment, forms a mineral substitute which has a solubility in acidic media of pH 4.2, which is below the solubility of hydroxyapatite.
  • the dental material can contain additives such as pigments, dyes, antioxidants, preservatives,
  • Fillers or other consistency-forming agents that can be added, for example, to adjust the rheology.
  • inert organic or organic fillers such as silicates, glasses, Zr0 2 , BaSÜ4, S1O2 and prepolymers, can be added to the dental material.
  • Fillers that can actively influence mineralization can also be used. Examples of these are ion-releasing glasses such as ionomer glasses and bioactive glasses, hydroxyapatite particles, amorphous calcium phosphate (ACP) or tetracalcium phosphate (TCP). Hydroxyla- Patite, in particular as a nanoparticle with an average particle diameter of 5-100 nm, is particularly preferred.
  • water-soluble particles from partner ions in particular calcium salts, phosphate and fluoride, in particular CaCl2 and (NH4) 2HPC> 4 particles, the mineral content and the ion reservoir for these species can be increased further.
  • Another preferred additive are water-soluble citrates.
  • Inorganic or organic color pigments can be added for coloring. These can be used to match the color of the material to the hard tooth substance or to introduce a contrast between the material and the tooth.
  • additives e.g. (Meth) acrylates or polyelectrolytes containing double bonds are introduced into the system.
  • the properties of the dental material described can also be influenced by the additional possibility of curing the polyelectrolyte system using a second curing mechanism.
  • the polymerizable monomer units can be crosslinked with the polyelectrolytes. Partial functionalization of the coacervates used is also possible.
  • aqueous solution is also to be understood as meaning those solutions which contain water in homogeneous solution with, for example, organic solvents.
  • Such solutions preferably contain more than 10% by weight of water, furthermore preferably more than 50% by weight of water, and the only solvent is particularly preferably water.
  • Polyelectrolytes are to be understood in particular as polymers which carry charged groups attached to the polymer chain directly or via spacer groups. Invited groups can participate be both negatively charged groups and positively charged groups. It is preferred that there are only charges of one sign on each polymer chain. The number of charged groups per polymer chain can vary within wide ranges.
  • the polymer chain of a suitable polyelectrolyte may contain monomer units that carry charge carriers as well as monomer units without charge carriers.
  • a suitable polyelectrolyte preferably has a solubility of more than 1 mg ml ⁇ 1 .
  • Coacervates are usually produced by exchanging the counterions of dissolved polyions with those that form coacervates with the polyion. Such a production step is already achieved by mixing the polyions dissolved in water with the corresponding coacervate-forming counterions dissolved in water. The resulting coacervates are then freed from excess residual ions by simple washing processes and can be isolated as syrupy to highly viscous or visco-elastic bodies.
  • the sodium salt of polyacrylic acid is mixed with CaCl2. Above a certain concentration of Ca 2+ ions in the solution and a corresponding ratio of Ca 2+ / carboxylate ratio, phase separation occurs and a liquid, water-containing coacervate can be isolated.
  • Coacervates can be used in liquid form in a continuous / macroscopic phase.
  • the variable water content is characteristic of the coacer according to the invention.
  • Water can be removed from the coacervate phase separated from the solution, for example until a solid is obtained. This dehydration is reversible.
  • the coacervates can then be used, preferably ground, as a powder.
  • the powders are preferably produced by drying and then grinding the dried coacervates. The drying takes place at temperatures below 250 ° C., preferably below 100 ° C., for example at 60 ° C. at normal pressure, 40 ° C. in a vacuum or preferably by freeze drying. Grinding is possible using a large number of the methods described in the prior art, dry or wet, in suitable liquid media. Use as suspensions or emulsions is also possible. Powder, suspension or emulsion are summarized below under the term finely divided forms.
  • coacervate a a coacervate based on anionic polyelectrolytes
  • coacervat b a coacervate based on cationic polyelectrolytes
  • the water-containing coacervate is based on polyacrylic acid and Ca 2+ ions.
  • phosphate can be used as the partner ion.
  • a solution in this form has proven to be favorable which contains (NH 4) 2 HPC> 4 in a concentration of 10 mM to 250 mM, preferably 130 mM.
  • the pH value also has a decisive influence on the formation of mineral substitutes. The pH value drops during mineralization without the use of additional powders.
  • the water-containing coacervate is based on polyallylamine and phosphate ions.
  • Ca 2+ ions can be used as partner ions. Solutions which contain CaCl2 in a concentration of 10 mM to 250 mM, particularly before given 130 mM, have proven to be beneficial for mineralization. The pH value also has a decisive influence on the formation of mineral substitutes in this embodiment.
  • the tooth surface is brought into contact with a solution containing the partner ion for a certain period of time.
  • the coacervate is then applied to this surface and flat (e.g. as a film) adapted, where it remains until sufficient mineralization of the tooth substance has taken place.
  • a coacervate of the other type can be applied to this.
  • the coacervate can on the one hand be applied as a viscous liquid. On the side facing away from the teeth, the arrangement can then be protected for the desired period of time so that the coacervate layer does not lose prematurely.
  • the coacervate can be applied in finely divided form to the tooth surface treated with the partner ion. It can also be used as a powder, as there is always a sufficient amount of water in the oral environment that is necessary for mineralization processes.
  • the coacervate is mixed in finely divided form with the solution of the partner ion and applied in this form to the tooth surface to be treated.
  • mineral replacement takes place based on the Boundaries of the coacervate particles take place, which can act on the tooth substance.
  • components containing the coacervates a) and b) can be mixed with one another as liquid components isolated in substance, which then form solid bodies very quickly.
  • the use of finely divided Coacerva, which are mixed in the presence of water when used, can be more favorable.
  • the processing and hardening time of such coacervate combinations can be controlled in each case by the choice of the particle or particle size distribution. It is also possible to apply coacervates in layers one after the other.
  • the finely divided components containing coacervates a) and b) are mixed in the presence of aqueous solutions and applied to the tooth substance to be treated. There they solidify primarily due to the formation of the insoluble interpolymer complexes. As the reaction progresses, the ions which form mineral substitutes are released from coacervates and mineral substitutes are formed in the area where the coacervate mixtures act and in the area of the hard tooth substance.
  • water or aqueous solutions must be added to the tooth substance in order to enable the reaction.
  • the admixture of water or aqueous solutions is preferably carried out before use on the tooth substance, for example by mixing in by hand or automatic methods such as mixing by capsule.
  • Powder and water or aqueous solution are preferably mixed in a weight ratio between 5: 1 to 1:50, preferably between 2: 1 to 1:10 and particularly preferably between 2: 1 to 1: 2.
  • a preferred form of these mixed powdered coacervates is a mixture of calcium polyacrylic acid coacervate with a polyallylamine phosphate coacervate.
  • a mass ratio of 1: 1 is favorable for this mixed coacervate.
  • Mass ratios of 5: 3 up to 3: 5 are also possible.
  • the amount of water to be added, if necessary, is based on the mixing consistency to be achieved, which is required in the respective application.
  • a non-aqueous dispersion of a mixture of the dried powders of the components is used with coacervates a) and b) in a completely water-miscible solvent (eg glycerine) mixed with another aqueous component before use.
  • a completely water-miscible solvent eg glycerine
  • the mixture is then applied to the tooth substance to be treated, where hardening and mineralization processes take place.
  • Salts to mix together before use This mixture is applied to the tooth substance to be treated, where hardening and mineralization processes also take place.
  • An aqueous emulsion of a coacervate or several coacervates as dental material contains at least 1 percent by weight, preferably at least 2 percent by weight, more preferably at least 5 percent by weight of coacervate.
  • Mixing can be carried out by hand or by using automatic mixing processes, for example by dispensing the two-component material from double cartridges and mixing them using a static or dynamic mixer.
  • the hard tooth substance to be treated is treated with an aqueous solution of a polyacid or a polybase or their salts before the application of the mixed components of the coacervates a) and b). It is particularly preferred to treat the surface of the tooth substance with a polyacid and then to apply the mixture of a) and b).
  • the aqueous solution is first used a polyacid is applied to the tooth substance and then that of the polybase before finally the mixture of a) and b) is applied.
  • the use of a polyacid or a polybase described here before the application of the dental material according to the invention is to be distinguished from the addition according to the invention of such a polyacid or polybase to the dental material according to the invention itself.
  • the dental material according to the invention forms a more intensive interaction with the hard tooth substance over time and thus counteracts a destabilizing effect on the adhesion caused by the effects of the environment.
  • Such an interaction can, for example, in the build-up of mineral substitute
  • the invention also relates to a kit for the produc- tion of a remineralizing dental material according to the invention, characterized by the following components: a first component which contains at least one coacervate with one of the partner ions as the counterion of the coacervate; a second component containing water; wherein the second of the partner ions is contained either as a free ion in aqueous solution in the second component and / or as a counterion of a second coacervate in one of the two components.
  • At least one of the components is preferably a solid, more preferably a powder.
  • At least one of the components is a liquid, preferably with a dynamic viscosity at 23 ° C. greater than 10 mPas, more preferably greater than 50 mPas, particularly preferably greater than 100 mPas.
  • At least two of the components are pastes.
  • At least two of the components are a gel.
  • At least one of the components preferably at least two of the components, has a pH of 7 to 9 at 23 ° C.
  • the kit preferably contains a further component c, which preferably has a pH of less than 7 and contains an adhesion promoter.
  • the adhesion promoter is preferably a poly acid or a polyamine, preferably at least 10% protonated.
  • the use of a polyacid or a polyamine described here before the application of the dental material according to the invention is to be distinguished from the addition of these materials according to the invention to the dental material according to the invention itself. According to the invention, it is also possible that such a component has a dual function Has adhesion promoter on the one hand and part of the dental material itself on the other hand.
  • Components a and b are preferably stored in a device suitable for mixing, preferably in a mixing capsule, preferably containing a powder and / or a liquid and / or a multiple cartridge, as part of a cartridge system for pressing out the components through a mixing cannula, preferably containing two pastes or two gels.
  • one of the partner ions is polyvalent and contained as a counterion in a coacervate, and a second partner ion is contained in an aqueous solution. At least one of the components also contains a second polyelectrolyte, which is charged differently than the polyelectrolyte of the coacervate.
  • component a contains at least one coacervate a) or b) and at least one polyelectrolyte which is charged differently than the polyelectrolyte of the coacervate and is not present as a coacervate.
  • component a contains at least one coacervate powder containing polyvalent anions as counterions and at least one powder of an anionic polyelectrolyte.
  • component a contains at least one coacervate powder containing polyvalent cations as counterions and at least one powder of a cationic polyelectrolyte.
  • component a contains at least one first coacervate powder containing alkaline earth metal ions, preferably calcium ions as counter ions and at least one second coacervate powder containing polyvalent anions as partner ions.
  • Another object of the invention is a method for using a kit according to the invention, comprising the steps: i. Application of component b to dentine and / or tooth enamel, preferably as a liquid ii. ii. Application of component a to dentine comprising component b and / or to tooth enamel comprising component b, preferably as a powder, paste, gel or viscous liquid.
  • the invention also relates to a method for using a kit according to the invention, comprising the steps: i. Mixing component a and component b, ii. Application of the mixture to dentine and / or tooth enamel, preferably as a paste or gel.
  • Another object of the invention is the use of the dental material according to the invention as a sealer, as a coating, as an underfill material and / or filling material, as an attachment cement, for pulp capping, as bone cement, as a dental varnish, as a fissure sealant, as a desensitizer, as a remineralization agent in prophylaxis or treatment of carious lesions; or for the production of such materia lien.
  • Embodiments of the invention are tert erläu below.
  • VT6025 stored at 40 ° C and 50 mbar for at least 24 hours.
  • the drying loss was calculated from the initial weight and the final weight.
  • thermogravimetric analysis was carried out in air from 25 ° C. to 1000 ° C. with a heating rate of 10 K / min (STA 449FS Ju piter, Netzsch).
  • the following devices were used to determine the element content: REM / EDX; TM 3000 Tabletop SEM, Hitachi and Quantax-EDX detector, Bruker). The freeze-dried powders were used.
  • the mold was placed on a glass plate and the dental material was placed in the holes. After the holes were filled with material, the openings of the holes were stripped flat.
  • the specimens were stored in the mold at 37 ° C. and approx. 100% relative humidity for 1 hour.
  • the test specimens including the mold were then taken out of the humidity chamber.
  • the mold was opened, the test specimens with a height of approx. 4 mm and a diameter of approx.
  • r the radius of the specimen, in millimeters; is.
  • the measurement was carried out for 6 test specimens in each case and the mean value was determined from the 6 measured values.
  • bovine incisors were embedded in a cold polymerizing resin without pulps (Viscovoss GTS with MEKP MEH hardener; Voss Chemie).
  • the embedded teeth were sanded down to the enamel or dentin wet (sandpaper P120) and then sanded wet with a fine sandpaper (P500).
  • the teeth were stored in demineralized water until they were used.
  • the teeth were taken from the demineralized water for the measurement.
  • a two-part Teflon mold with a bore of 3.0 mm was then made Diameter (ISO / TS 11405: 2003) attached, fixed with a metal clamp and the cavity filled with the dental material.
  • the viscosity was measured at 23 ° C. by means of a dynamic plate-plate viscometer (Dynamic Stress Rheometer, Rheometric Scientific Inc.). Shear stress was measured in the “steady stress sweep” mode with gap sizes of 0.1 to 0.5 mm in the range from 0 to 50 Pa.
  • the dental material from Ex. 6 was cured in a thin layer.
  • the material was then stored in the humidity chamber at 37 ° C. for 5 days.
  • the dried material was ground in a mortar and examined in this form by X-ray diffraction (Bruker D8, Discover).
  • the mixture was centrifuged, decanted and washed three times with 1.75 ultrapure water each time.
  • the washed residues from the centrifugation were then dried at 37.degree.
  • the dried products) were each examined as a powder by means of X-ray diffraction (XRD) for their mineral phases.
  • the pH values were each adjusted using hydrochloric acid and / or sodium hydroxide solutions.
  • the quantities, concentrations and pH values of the solutions used are given in Table 1.
  • Table 1 Quantities, concentrations and pH values of the solutions used for the coacervate synthesis
  • the pH values were each adjusted using hydrochloric acid and / or sodium hydroxide solutions.
  • the amounts, concentrations and pH values of the solutions used are given in Table 2.
  • the ion content was determined as the element content by means of energy dispersive X-ray spectroscopy (EDX).
  • the residual water content of the freeze-dried viscous gels was determined by means of thermogravimetry (TGA). Residual water contents and element contents are given in Table 3b a.
  • Table 3b Residual water content determined by TGA and element content determined by EDX of freeze-dried coacervates
  • Example 1 The viscous liquid from Example 1 was removed by freeze drying water. The material obtained in this way was stirred for 7 hours in a vibration mill (Pulverisette 0, Fritsch), then for 6 hours in a mortar mill (Pulverisette 2, Fritsch) and finally for 18 hours in a ball mill (ball distribution: 55 x 16 mm, 14 x 25 mm, 4 x 40 mm) ground.
  • a vibration mill Pulverisette 0, Fritsch
  • a mortar mill Pulverisette 2, Fritsch
  • ball mill ball distribution: 55 x 16 mm, 14 x 25 mm, 4 x 40 mm
  • the residual water content of the white powder obtained was determined by means of TGA.
  • the residual water content was 8% by weight.
  • Example 5 The viscous liquid from Example 5 was removed by freeze drying water.
  • the material obtained in this way was stirred for 7 h in a vibration mill (Pulverisette 0, Fritsch), then for 60 s in a capsule mixer (1 ml; ball diameter: 3.15 mm; Silamat, Ivoclar-Vivadent) and finally ground for 60 s in a capsule mixer (1 ml; ball diameter: 0.1 mm; Silamat, Ivoclar-Vivadent).
  • the residual water content of the white powder obtained was determined by means of TGA. The residual water content was 8% by weight.
  • This powder is the second, cationic polyelectrolyte, which according to the invention can be used together with a coacervate with anionic polyelectrolyte and promotes deep mineralization in the manner already mentioned above and shown in the examples.
  • Example 6
  • the powder and the liquid were mixed for 20 seconds using a vibratory mixer (Silamat, Ivoclar Vivadent AG) to form an application-ready treatment material.
  • the resulting treatment material was discharged from the mixing capsule via the cannula of the mixing capsule and was processed.
  • the compressive strength was determined for the dental materials of Examples 6-8.
  • the compressive strengths are given in Table 4.
  • the compressive strength was highest for the material of Example 7.
  • the compressive strengths of all dental materials were higher after 4 days than 1 hour after processing.
  • the dental material is self-adhesive. Cracks formed in the specimens or the specimens deformed before they were sheared off.
  • model substances for demineralized dentin were first produced.
  • Each model substance consists of a gel that is solid at room temperature.
  • 10 g of gelatin A-type, 300 bloom
  • 10 g of gelatin were dissolved in 90 ml of an aqueous solution with a pH equal to 9 and containing 130 mM diammonium hydrogen phosphate and 100 mM tri-sodium citrate tetrahydrate.
  • the resulting gelatin solution was filled into standard 24-well titer plates and allowed to cool to room temperature.
  • the solid gel bodies were removed from the titer plate with the aid of a spatula and stored in the aqueous solution.
  • the dental materials were each applied to the surface of the model substance, i.e. H. applied to the top of the disk-shaped gel body and stored at room temperature in 10 ml of the aqueous solution (containing 130 M diammonium hydrogen phosphate and 100 mM tri-sodium citrate tetrahydrate, pH 9) so that the dental material and the model substance were covered by the solution or they were in Climatic cabinet stored at 100% humidity and room temperature.
  • the gel bodies were removed and washed with ultrapure water.
  • Cross sections of the disk-shaped gel body were then made with a razor blade. The cross-sections were visually checked to determine whether mineralized material could be seen under the model substance surface and how deep it reached into the model substance.
  • Self-adhesive, self-curing dental materials were produced analogously to Example 6.
  • the powder / powder mixtures and liquids used are shown in Table 6 below.
  • the liquid component used is the aqueous solution that contains (NH 4) 2HPO4 and sodium citrate, as already used in Example 8.
  • the powder mixture contains powder P3 as the second, cationic polyelectrolyte, which is used together with the coacervate with anionic polyelectrolyte (powder P1) and promotes deep mineralization in the manner already mentioned above.
  • the dental material 150 mg of the respective powder / powder mixture and the liquid component were placed separately from one another in a mixing capsule (Applicap, DMG Hamburg). The powder and the liquid were mixed for 20 seconds using a vibratory mixer (Silamat, Ivoclar Vivadent AG) to form a ready-to-use treatment material. Immediately after mixing, the resulting treatment material was discharged from the mixing capsule via the cannula of the mixing capsule and processed.
  • the dental materials produced in this way were applied to model substance according to the application examples below and the mineralization was tested.
  • the dental material of Table 6 above, Example 11 was applied to the model substance and stored in the aqueous solution as described. After 4 days, there was a slight deep mineralization. After 12 days, only a slight deep mineralization was observed (Fig.l). For the mineral formed in the gelatin, calcium, carbon, phosphorus and oxygen were detected over the entire depth (Fig. 2). The mineral was identified as hydroxyapatite by means of XRD (FIG. 3).
  • Example 12 The dental material of Table 6 above, Example 12, was applied to the model substance and stored in the aqueous solution as described.
  • Example 13 The dental material of Table 6 above, Example 13, was applied to the model substance and stored in the climate chamber as described.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Chemical & Material Sciences (AREA)
  • Birds (AREA)
  • Inorganic Chemistry (AREA)
  • Plastic & Reconstructive Surgery (AREA)
  • Dispersion Chemistry (AREA)
  • Dental Preparations (AREA)

Abstract

L'invention a pour objet un matériau dentaire de reminéralisation comportant au moins respectivement un cation et un anion, qui sont réalisés sous forme d'ions partenaires pour former une substance de reminéralisation. Selon l'invention, au moins l'un des ions partenaires est plurivalent et est contenu dans un coacervat sous forme de contre-ion. L'invention a également pour objet un kit de production d'un tel matériau dentaire ainsi que son application.
EP20720901.6A 2019-04-08 2020-04-08 Matériau dentaire de reminéralisation Pending EP3952818A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102019109150.0A DE102019109150A1 (de) 2019-04-08 2019-04-08 Remineralisierendes Dentalmaterial
PCT/EP2020/000081 WO2020207618A1 (fr) 2019-04-08 2020-04-08 Matériau dentaire de reminéralisation

Publications (1)

Publication Number Publication Date
EP3952818A1 true EP3952818A1 (fr) 2022-02-16

Family

ID=70416431

Family Applications (1)

Application Number Title Priority Date Filing Date
EP20720901.6A Pending EP3952818A1 (fr) 2019-04-08 2020-04-08 Matériau dentaire de reminéralisation

Country Status (9)

Country Link
US (1) US20220202655A1 (fr)
EP (1) EP3952818A1 (fr)
JP (1) JP2022527008A (fr)
KR (1) KR20220005445A (fr)
CN (1) CN113905710B (fr)
BR (1) BR112021019702A2 (fr)
CA (1) CA3136146A1 (fr)
DE (1) DE102019109150A1 (fr)
WO (1) WO2020207618A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023201001A1 (fr) * 2022-04-15 2023-10-19 Zest Ip Holdings, Llc Composition de reminéralisation et procédé d'application associé
CN115154331B (zh) * 2022-06-16 2024-01-16 武汉大学 一种具有介孔核壳结构的牙本质矿化脱敏材料及其制备方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2224274C (fr) * 1995-08-08 2001-07-31 Enamelon, Inc. Produits et procedes de remineralisation des dents
CN101115459B (zh) * 2004-11-16 2012-03-21 3M创新有限公司 包括含磷表面处理的牙科填料
CN101410022B (zh) * 2006-02-03 2013-06-12 Wm.雷格利Jr.公司 在适用作牙齿再矿化剂的口腔用组合物中的钙的磷酸盐
EP2424488B1 (fr) * 2009-04-27 2023-06-07 Premier Dental Products Company Compositions microencapsulées et procédés de minéralisation tissulaire
WO2017209823A2 (fr) * 2016-03-14 2017-12-07 The University Of Chicago Pâtes injectables à base de nanoparticules hybrides de phosphate de calcium et de polymère de charges opposées
US20190083363A1 (en) 2016-03-17 2019-03-21 The Regents Of The University Of California Compositions for the remineralization of dentin

Also Published As

Publication number Publication date
US20220202655A1 (en) 2022-06-30
CA3136146A1 (fr) 2020-10-15
CN113905710A (zh) 2022-01-07
KR20220005445A (ko) 2022-01-13
BR112021019702A2 (pt) 2021-12-14
DE102019109150A1 (de) 2020-10-08
WO2020207618A1 (fr) 2020-10-15
CN113905710B (zh) 2024-07-16
JP2022527008A (ja) 2022-05-27

Similar Documents

Publication Publication Date Title
DE2439882C3 (de) Anrührflüssigkeit für selbsthärtende Zementmassen
EP2170245B1 (fr) Matériau d'implant à base de ciment hydraulique et utilisation de celui-ci
DE68915265T2 (de) Ärztliches und zahnärztliches vernetzbares material.
DE10028975B4 (de) Zusammensetzungen zur Behandlung von Zahn- und/oder Knochengewebe
DE3934008C2 (de) Füllmassen für provisorische Zahnfüllungen
EP2236162B1 (fr) Ciment osseux bioactif et son procédé de fabrication
EP3952818A1 (fr) Matériau dentaire de reminéralisation
DE2750326A1 (de) Zementmassen fuer zahnmedizinische und orthopaedische anwendungszwecke
DE2101939C3 (de) Durch Zusatz von Zinkoxid härtende Massen
DE3510234A1 (de) Chirurgische zemente und verfahren zu ihrer herstellung
WO2003000588A1 (fr) Cristaux d'apatite en forme de baguette a rapport longueur sur largeur determine
DE1492247A1 (de) Verfahren zum Wiederverhaerten von Zahnschmelz und dafuer geeignetes Zahnpflegemittel
EP2768543B1 (fr) Préparation pour la fabrication d'un implant
RU2800094C2 (ru) Реминерализационный стоматологический материал
WO2019185175A1 (fr) Ciment dentaire durcissable à l'eau, procédé et kit de préparation d'un tel ciment dentaire durcissable à l'eau et utilisation correspondante
DE102005003755B4 (de) Beschichtete Dentalpulver
EP4009937A1 (fr) Préparation et matériau entièrement composé destiné à être utilisé dans des applications médicales ou dentaires, produit médical ou dentaire et son utilisation et sa préparation
DE3935060A1 (de) Bioaktives keramisches material fuer zahnfuellungen und -kronen
DE10101301B4 (de) Wasserbasierender Zement
CH705253B1 (de) Mineralhaltige Heilpaste.
DE102019005401A1 (de) Füllmaterial zur schliessung von kavitäten und kanälen in biologischem hartgewebe
DE3511721A1 (de) Granulierte alginat-abformmassen
EP4335466A1 (fr) Composition destinée à la production d'une matière de substitution osseuse, procédé de production d'un véhicule pharmaceutique de principe actif, véhicule pharmaceutique de principe actif, ainsi que son utilisation
DE10130121A1 (de) Stäbchenförmige Apatitkristalle mit einem bestimmten Länge-zu-Breite-Verhältnis
DE1903087B (de) Pulverförmige Dentalzement-Vormischung

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20211018

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230516