WO2022090112A1 - Specific kit comprising a specific fat soluble vitamin formulation and a formulation of specific human milk oligosaccharides - Google Patents

Specific kit comprising a specific fat soluble vitamin formulation and a formulation of specific human milk oligosaccharides Download PDF

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Publication number
WO2022090112A1
WO2022090112A1 PCT/EP2021/079455 EP2021079455W WO2022090112A1 WO 2022090112 A1 WO2022090112 A1 WO 2022090112A1 EP 2021079455 W EP2021079455 W EP 2021079455W WO 2022090112 A1 WO2022090112 A1 WO 2022090112A1
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WO
WIPO (PCT)
Prior art keywords
kit
container
kit according
delivery system
anyone
Prior art date
Application number
PCT/EP2021/079455
Other languages
French (fr)
Inventor
Elger Funda
Zdravka MISIC
Araksya TOPCHYAN
Original Assignee
Dsm Ip Assets B.V.
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Publication date
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Publication of WO2022090112A1 publication Critical patent/WO2022090112A1/en

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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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Definitions

  • the present invention relates to a specific kit comprising a specific fat soluble vitamin formulation and a formulation of specific human milk oligosaccharides (HMO), which is used in the treatment, prevention or prophylaxis of norovirus infections.
  • HMO human milk oligosaccharides
  • Noroviruses are positive-sense single-stranded RNA viruses that cause most cases of non-bacterial acute gastroenteritis in all age groups. Norovirus, sometimes referred to as the winter vomiting bug, is the most common cause of gastroenteritis.
  • the infection is characterized by non-bloody diarrhea, vomiting, and stomach pain. Fever or headaches may also occur. Symptoms usually develop 12 to 48 hours after being exposed, and recovery typically occurs within 1 to 3 days.
  • Noroviruses are recognized as one of the most important causes of infection of unknown viral etiology, especially in adults.
  • Norovirus results in about 685 million cases of disease and 200,000 deaths globally a year. Those under the age of five are most often affected, and in this group it results in about 50,000 deaths.
  • the virus is named after the city of Norwalk, Ohio, (USA) where an outbreak occurred in 1968.
  • the goal was to find a useful tool for the treatment, prevention or prophylaxis of norovirus infections.
  • kit comprising a specific fat-soluble vitamin formulation and at least one HMO. Therefore the present invention relates to a kit (K) comprising:
  • a solid core which comprises at least one fat-soluble vitamin
  • the kit according to the present invention is used in the treatment, prevention or prophylaxis of norovirus infections.
  • Container in the sense of the present invention is any container usually used for such an use.
  • kits are known in the art for holding and dispensing pharmaceutical agents for periodic oral use.
  • the package comprises indicators for each administration period.
  • the package comprises a labeled blister package, dial dispenser package, or bottle.
  • the kits of the disclosure can also comprise a means for containing any type of packaging that houses the unit dosage forms, for example bottles or vials, which can (for example) be held in close confinement for commercial sale such as, e.g., injection or blow-molded plastic containers into which the bottles or vials are retained. Any material can be used for such containers (such as plastic, glass or any mixture of materials).
  • nutraceuticals can be incorporated into the core (or the coatings).
  • the present invention relates to a kit (K1), which is the kit (K), wherein the solid core of the solid formulation in the first container comprises at least one fat soluble vitamin chosen from the group consisting of vitamin A, D, E and K (as well as any commonly used derivative of these vitamins). Vitamin A (as well as its derivates (such as vitamin A palmitate or acetate) are most preferred).
  • the solid formulation (which is in the first container of the kit) is a delivery system which comprises an inner coating, which needs to fulfill the criteria as defined.
  • Suitable materials for the inner coating are for example alginate, chitosan, pectin, cyclodextrin as well as other gums.
  • Preferred coating materials for the inner coating are alginate or pectin.
  • the inner coating is crosslinked. This can be done by commonly known crosslinking compounds. In case alginate is used that can be done by Zn, Mg and/or Ca ions (by the use of a salt).
  • the crosslinker can be sprayed onto the solid core after having applied the inner coating or simultaneously. Or the coated particles can be dipped into a solution comprising the crosslinker.
  • crosslinker is sprayed onto the particles after having applied the inner coating layer.
  • kits (K2) which is the kit (K) or (K1), wherein the material of the inner coating of the solid formulation in the first container is chosen from group consisting of alginate, chitosan, pectin, cyclodextrin as well as other gums.
  • kits (K2’) which is the kit (K2), wherein the material of the inner coating of the solid formulation in the first container is alginate or pectin.
  • the inner coating layer is covering the core (more or less) completely. Ideally the (layer of the inner coating has (more or less) the same thickness when applied on the solid core. Usually the thickness of the inner coating layer is at least 5pm and not more than 20 .m. Preferably, the thickness of the inner coating layer is between 5pm - 10pm.
  • kits (K3) which is the kit (K), (K1), (K2) or (K2’), wherein the thickness of the inner coating layer of the solid formulation in the first container is 5pm - 10pm.
  • the inner coating layer is crosslinked with at least one crosslinking agent. Any suitable crosslinker can be used. Very suitable (and therefore preferred are Zn, Mg and Ca ions (they are added in form of a salt).
  • kits (K4) which is the kit (K), (K1), (K2), (DS2’) or (K3), wherein the inner coating layer of the solid formulation in the first container is crosslinked with at least one crosslinking agent (preferably with Zn, Mg and/or Ca ions).
  • kits (K5) which is the kit (K), (K1), (K2), (DS2’), (K3) or (K4), wherein the crosslinked inner coating layer of the solid formulation in the first container is Na alginate or pectin.
  • the delivery system in the first container of the kit according to the present invention comprises an outer coating, which needs to fulfill the criteria as defined.
  • Suitable materials which fulfill the criteria for the outer coating is for example shellac, methacrylate copolymers and fats.
  • kits (K6) which is the kit (K), (K1), (K2), (K2’), (K3), (K4) or (K5), wherein the material of the outer coating of the solid formulation in the first container is chosen from group consisting of shellac, methacrylate copolymers and fats.
  • the outer coating layer is covering the inner coating (more or less) completely. Ideally the layer of the outer coating has (more or less) the same thickness when applied on the inner coating.
  • the thickness of the outer layer is at least 10pm and usually less than 30 pm.
  • the thickness of the outer coating layer is between 10 and 20pm.
  • the solid core of the delivery system in the first container of the kit according to the present invention is usually 50 - 85 wt- %, preferably 55 - 75 wt-%, based on the total weight of the delivery system.
  • the inner coating of the delivery system in the first container according to the present invention is usually 1 - 20 wt- %, preferably 5 - 15 wt-%, based on the total weight of the delivery system.
  • the outer coating of the delivery system according to the present invention is usually 1 - 30 wt- %, preferably 15 - 30 wt-%, based on the total weight of the delivery system.
  • the delivery stem in the first container is a delivery system comprising
  • the delivery system in the first container is a delivery system comprising
  • the delivery stem in the first container is a delivery system consisting of
  • the delivery system in the first container is a delivery system consisting of (a) 55 - 75 wt- %, based on the total weight of the delivery system, of a solid core, and
  • kits (K7) which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5) or (K6), wherein the thickness of the outer coating of the solid formulation in the first container layer is 10pm - 20pm.
  • kits (K8) which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6) or (DS7), wherein the solid core of the delivery system of the solid formulation in the first container is 50 - 85 wt- %, preferably 50 - 75 wt-%, based on the total weight of the delivery system.
  • kits (K9) which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7) or (K8), wherein the inner coating of the delivery system in the first container is 10 - 20 wt- %, preferably 5 - 15 wt-%, based on the total weight of the delivery system.
  • kits (K10) which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8) or (K9), wherein the outer coating of the delivery system in the first container is 1 - 30 wt- %, preferably 15 - 30 wt-%, based on the total weight of the delivery system
  • the delivery system in the first container of the kit according to the present invention can be up to 2mm in size.
  • the size is defined by the longest diameter of the particle.
  • the shape of the particle is not an essential feature of the present invention. Also, the size distribution of the particles is not essential.
  • the size and the shape of the particle is mainly defined by the solid core of the delivery system. Depending on the use of the delivery system the size can be adjusted.
  • the delivery system according in the first container of the kit according to the present invention is produced by commonly known technology.
  • the solid core is produced in a first step and then the inner and outer coatings are applied.
  • the solid core particles can be produced by known methods, such as spray-drying, agglomeration, granulation, micro-tableting, extrusion or extrusion-spheronization.
  • the new delivery system can be produced batch-wise of continuously.
  • the new particles can be produced as follows:
  • the solid cores are coated by spray coating with the coating material of the inner coating, and then the crosslinker is sprayed onto the particle.
  • the outer coating is sprayed onto the particle obtained by the previous steps and finally the particles are dried.
  • the advantage of the process is that the steps, including the generation of solid cores by granulation or agglomeration, can be carried out in the same apparatus (fluid-bed processor) which reduces the technical effort. Nevertheless, it is also possible to i.e. produce the solid cores first, store them and then coat them.
  • Another option how to produce the new delivery system is a continuous process, wherein the solid cores are produced first and then the coating steps are done spray onto the particle one after the other. These processes are ideal to apply in an industrial scale.
  • HMO human milk oligosaccharide
  • HMOs Human milk oligosaccharides
  • HMOs are composed of the five monosaccharides glucose (Glc), galactose (Gal), N- acetylglucosamine (GIcNAc), fucose (Fuc) and sialic acid (Sia), with N-acetylneuraminic acid (Neu5Ac) as the predominant if not only form of Sia. More than two hundred different HMOs have been identified so far. The most important are 2 '-fucosy I lactose (2' FL), lacto- N-neotetraose (LNnT) and 3-fucosyllactose (3FL).
  • HMOs can be isolated from breast milk or it can be produced chemically or biochemically. HMOs are available commercially from a variety of producers.
  • the source of the HMO is not essential. It is clear that HMOs from different sources can be used.
  • HMO or the mixture of HMOs are in the form of a powder in the second container, which is dissolved in suitable solvent before consumption.
  • the HMO or the mixture of HMOs in the second container is in a compressed form (like a tablet or beadlet) of in any other form (even liquid or gel-like).
  • kits (K11) which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8), (K9) or (K10), wherein the second container comprises at least one HMO selected from the group consisting of 2'-fucosyllactose (2' FL), lacto-N- neotetraose (LNnT) and 3-fucosyllactose (3FL).
  • 2'-fucosyllactose 2' FL
  • lacto-N- neotetraose LNnT
  • 3-fucosyllactose 3-fucosyllactose
  • the kit according to the present invention can also comprise an outer packaging, which is a kit case.
  • Method of producing a kit comprising the step: production of tablets comprising solid formulation of the invention and filling then in blisters, sachets or any other suitable packing.
  • solid formulation in the form of powder (no tablet form). Then it needs to be packed in some kind of a sachet.
  • sachets which comprise the HMO (or mixture of HMO). It is also possible to have the HMO in a “non-powder” form.
  • kit which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8), (K9), (K10) or (K11), wherein the kit comprises an outer packaging.
  • That outer packing can be any kind of usually used material or combination of material (paper, plastic, glass, etc).
  • the outer packing can be useful for the protection of the kit and/or nice appearance of the kit. For the purpose of storing the kit such an outer packing may also be useful.
  • the kit according to the present invention can also comprise instructions for use.
  • kits (K13) which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8), (K9), (K10), (K11) or (K12), wherein the kit instructions for use.
  • the instructions may be in the form of a leaflet of may be printed on the kit or on the outer packing.
  • the present invention relates to a method of treatment, prevention or prophylaxis of norovirus infections using the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8), (K9), (K10), (K11) or (K12).
  • Step 1 production of tablets comprising formulation of invention and filling in blister
  • Step 2 production of sachets, comprising HMO
  • Step 3 production of kit by filling an empty kit case with 10 sachets of step 2 and a blister of step 1 comprising 10 tablets
  • Step 4 adding a package leaflet to the filled kit case of step 3

Abstract

The present invention relates to a specific kit comprising a specific fat soluble vitamin formulation and a formulation of specific human milk oligosaccharides (HMO), which is used in the treatment, prevention or prophylaxis of norovirus infections.

Description

specific kit comprising a specific fat soluble vitamin formulation and a formulation of specific human milk oligosaccharides
The present invention relates to a specific kit comprising a specific fat soluble vitamin formulation and a formulation of specific human milk oligosaccharides (HMO), which is used in the treatment, prevention or prophylaxis of norovirus infections.
Noroviruses (genus Norovirus, family Caliciviridae) are positive-sense single-stranded RNA viruses that cause most cases of non-bacterial acute gastroenteritis in all age groups. Norovirus, sometimes referred to as the winter vomiting bug, is the most common cause of gastroenteritis.
The infection is characterized by non-bloody diarrhea, vomiting, and stomach pain. Fever or headaches may also occur. Symptoms usually develop 12 to 48 hours after being exposed, and recovery typically occurs within 1 to 3 days.
Young persons, old person, and those with other health problems may also suffer from complications, such as i.e. dehydration.
Noroviruses are recognized as one of the most important causes of infection of unknown viral etiology, especially in adults.
Norovirus results in about 685 million cases of disease and 200,000 deaths globally a year. Those under the age of five are most often affected, and in this group it results in about 50,000 deaths.
The virus is named after the city of Norwalk, Ohio, (USA) where an outbreak occurred in 1968.
Due to the large cases of infection, there is always a need to decrease the number of infected persons.
Therefore, the goal was to find a useful tool for the treatment, prevention or prophylaxis of norovirus infections.
Surprisingly, it was found that kit comprising a specific fat-soluble vitamin formulation and at least one HMO. Therefore the present invention relates to a kit (K) comprising:
(a) a first container comprising a solid formulation consisting of
(i) a solid core, which comprises at least one fat-soluble vitamin, and
(ii) an inner coating comprising at least one fermentable biopolymer, which is crosslinked, and
(iii) an outer coating which is resistant to stomach conditions and releasing in the small intestine, b) a second container comprising at least one human milk oligosaccharide.
The kit according to the present invention is used in the treatment, prevention or prophylaxis of norovirus infections.
Container in the sense of the present invention is any container usually used for such an use.
Suitable packages or containers are known in the art for holding and dispensing pharmaceutical agents for periodic oral use. In one embodiment, the package comprises indicators for each administration period. In another embodiment, the package comprises a labeled blister package, dial dispenser package, or bottle. The kits of the disclosure can also comprise a means for containing any type of packaging that houses the unit dosage forms, for example bottles or vials, which can (for example) be held in close confinement for commercial sale such as, e.g., injection or blow-molded plastic containers into which the bottles or vials are retained. Any material can be used for such containers (such as plastic, glass or any mixture of materials).
If needed and wished, other nutraceuticals can be incorporated into the core (or the coatings).
Therefore, the present invention relates to a kit (K1), which is the kit (K), wherein the solid core of the solid formulation in the first container comprises at least one fat soluble vitamin chosen from the group consisting of vitamin A, D, E and K (as well as any commonly used derivative of these vitamins). Vitamin A (as well as its derivates (such as vitamin A palmitate or acetate) are most preferred). The solid formulation (which is in the first container of the kit) is a delivery system which comprises an inner coating, which needs to fulfill the criteria as defined. Suitable materials for the inner coating (fermentable biopolymer) are for example alginate, chitosan, pectin, cyclodextrin as well as other gums. Preferred coating materials for the inner coating are alginate or pectin.
The inner coating is crosslinked. This can be done by commonly known crosslinking compounds. In case alginate is used that can be done by Zn, Mg and/or Ca ions (by the use of a salt). The crosslinker can be sprayed onto the solid core after having applied the inner coating or simultaneously. Or the coated particles can be dipped into a solution comprising the crosslinker.
Preferably the crosslinker is sprayed onto the particles after having applied the inner coating layer.
Therefore, the present invention relates to a kit (K2), which is the kit (K) or (K1), wherein the material of the inner coating of the solid formulation in the first container is chosen from group consisting of alginate, chitosan, pectin, cyclodextrin as well as other gums.
Therefore, the present invention relates to a kit (K2’), which is the kit (K2), wherein the material of the inner coating of the solid formulation in the first container is alginate or pectin.
The inner coating layer is covering the core (more or less) completely. Ideally the (layer of the inner coating has (more or less) the same thickness when applied on the solid core. Usually the thickness of the inner coating layer is at least 5pm and not more than 20 .m. Preferably, the thickness of the inner coating layer is between 5pm - 10pm.
Therefore, the present invention relates to a kit (K3), which is the kit (K), (K1), (K2) or (K2’), wherein the thickness of the inner coating layer of the solid formulation in the first container is 5pm - 10pm. The inner coating layer is crosslinked with at least one crosslinking agent. Any suitable crosslinker can be used. Very suitable (and therefore preferred are Zn, Mg and Ca ions (they are added in form of a salt).
Therefore, the present invention relates to a kit (K4), which is the kit (K), (K1), (K2), (DS2’) or (K3), wherein the inner coating layer of the solid formulation in the first container is crosslinked with at least one crosslinking agent (preferably with Zn, Mg and/or Ca ions).
Therefore, the present invention relates to a kit (K5), which is the kit (K), (K1), (K2), (DS2’), (K3) or (K4), wherein the crosslinked inner coating layer of the solid formulation in the first container is Na alginate or pectin.
The delivery system in the first container of the kit according to the present invention comprises an outer coating, which needs to fulfill the criteria as defined. Suitable materials which fulfill the criteria for the outer coating is for example shellac, methacrylate copolymers and fats.
Therefore, the present invention relates to a kit (K6), which is the kit (K), (K1), (K2), (K2’), (K3), (K4) or (K5), wherein the material of the outer coating of the solid formulation in the first container is chosen from group consisting of shellac, methacrylate copolymers and fats.
The outer coating layer is covering the inner coating (more or less) completely. Ideally the layer of the outer coating has (more or less) the same thickness when applied on the inner coating.
Usually the thickness of the outer layer is at least 10pm and usually less than 30 pm. Preferably, the thickness of the outer coating layer is between 10 and 20pm.
The solid core of the delivery system in the first container of the kit according to the present invention is usually 50 - 85 wt- %, preferably 55 - 75 wt-%, based on the total weight of the delivery system. The inner coating of the delivery system in the first container according to the present invention is usually 1 - 20 wt- %, preferably 5 - 15 wt-%, based on the total weight of the delivery system.
The outer coating of the delivery system according to the present invention is usually 1 - 30 wt- %, preferably 15 - 30 wt-%, based on the total weight of the delivery system.
It is clear that the addition of the percentages of the solid core and the inner coating and the outer coating of one delivery system always adding up to 100%.
This means that the delivery stem in the first container is a delivery system comprising
(a) 50 - 85 wt- %, based on the total weight of the delivery system, of a solid core, and
(b) 1 - 20 wt- %, based on the total weight of the delivery system, of an inner coating, and
(c) 1 - 30 wt- %, based on the total weight of the delivery system, of an outer coating.
Preferably the delivery system in the first container is a delivery system comprising
(a) 55 - 75 wt- %, based on the total weight of the delivery system, of a solid core, and
(b) 5 - 15 wt-%, based on the total weight of the delivery system, of an inner coating, and
(c) 15 - 30 wt-%, based on the total weight of the delivery system, of an outer coating.
This means that the delivery stem in the first container is a delivery system consisting of
(a) 50 - 85 wt- %, based on the total weight of the delivery system, of a solid core, and
(b) 1 - 20 wt- %, based on the total weight of the delivery system, of an inner coating, and
(c) 1 - 30 wt- %, based on the total weight of the delivery system, of an outer coating.
Preferably the delivery system in the first container is a delivery system consisting of (a) 55 - 75 wt- %, based on the total weight of the delivery system, of a solid core, and
(b) 5 - 15 wt-%, based on the total weight of the delivery system, of an inner coating, and
(c) 15 - 30 wt-%, based on the total weight of the delivery system, of an outer coating.
Therefore, the present invention relates to a kit (K7), which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5) or (K6), wherein the thickness of the outer coating of the solid formulation in the first container layer is 10pm - 20pm.
Therefore, the present invention relates to a kit (K8), which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6) or (DS7), wherein the solid core of the delivery system of the solid formulation in the first container is 50 - 85 wt- %, preferably 50 - 75 wt-%, based on the total weight of the delivery system.
Therefore, the present invention relates to a kit (K9), which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7) or (K8), wherein the inner coating of the delivery system in the first container is 10 - 20 wt- %, preferably 5 - 15 wt-%, based on the total weight of the delivery system.
Therefore, the present invention relates to a kit (K10), which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8) or (K9), wherein the outer coating of the delivery system in the first container is 1 - 30 wt- %, preferably 15 - 30 wt-%, based on the total weight of the delivery system
The delivery system in the first container of the kit according to the present invention can be up to 2mm in size. The size is defined by the longest diameter of the particle. The shape of the particle is not an essential feature of the present invention. Also, the size distribution of the particles is not essential. The size and the shape of the particle is mainly defined by the solid core of the delivery system. Depending on the use of the delivery system the size can be adjusted. The delivery system according in the first container of the kit according to the present invention is produced by commonly known technology.
Usually the solid core is produced in a first step and then the inner and outer coatings are applied.
The solid core particles can be produced by known methods, such as spray-drying, agglomeration, granulation, micro-tableting, extrusion or extrusion-spheronization.
As disclosed above one of the major advantages of the new delivery system (besides the property of the delivery system) lies in the process of production of the delivery system. The new delivery system can be produced batch-wise of continuously.
When produced batch-wise the new particles can be produced as follows:
In a first step the solid cores are coated by spray coating with the coating material of the inner coating, and then the crosslinker is sprayed onto the particle. In a second step the outer coating is sprayed onto the particle obtained by the previous steps and finally the particles are dried.
The advantage of the process is that the steps, including the generation of solid cores by granulation or agglomeration, can be carried out in the same apparatus (fluid-bed processor) which reduces the technical effort. Nevertheless, it is also possible to i.e. produce the solid cores first, store them and then coat them.
Another option how to produce the new delivery system is a continuous process, wherein the solid cores are produced first and then the coating steps are done spray onto the particle one after the other. These processes are ideal to apply in an industrial scale.
In the second container of the kit according of the present invention there is at least one human milk oligosaccharide (HMO).
Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that are highly abundant in and unique to human milk. Originally, HMOs were proposed to be prebiotic "bifidus factors," or human milk glycans found to promote growth in Bifidobacterial species of the gut and found uniquely in the stool of breast fed infants compared to formula fed infants.
HMOs are composed of the five monosaccharides glucose (Glc), galactose (Gal), N- acetylglucosamine (GIcNAc), fucose (Fuc) and sialic acid (Sia), with N-acetylneuraminic acid (Neu5Ac) as the predominant if not only form of Sia. More than two hundred different HMOs have been identified so far. The most important are 2 '-fucosy I lactose (2' FL), lacto- N-neotetraose (LNnT) and 3-fucosyllactose (3FL).
HMOs can be isolated from breast milk or it can be produced chemically or biochemically. HMOs are available commercially from a variety of producers.
For the purpose of the present invention the source of the HMO is not essential. It is clear that HMOs from different sources can be used.
Usually the HMO or the mixture of HMOs are in the form of a powder in the second container, which is dissolved in suitable solvent before consumption.
But it is also possible that the HMO or the mixture of HMOs in the second container is in a compressed form (like a tablet or beadlet) of in any other form (even liquid or gel-like).
Therefore, the present invention relates to a kit (K11), which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8), (K9) or (K10), wherein the second container comprises at least one HMO selected from the group consisting of 2'-fucosyllactose (2' FL), lacto-N- neotetraose (LNnT) and 3-fucosyllactose (3FL).
The kit according to the present invention can also comprise an outer packaging, which is a kit case.
Method of producing a kit, said method comprising the step: production of tablets comprising solid formulation of the invention and filling then in blisters, sachets or any other suitable packing. Alternatively, it is also possible to use the solid formulation in the form of powder (no tablet form). Then it needs to be packed in some kind of a sachet.
Production of sachets, which comprise the HMO (or mixture of HMO). It is also possible to have the HMO in a “non-powder” form.
Then production of kit by filling an empty kit case with a certain amount of sachets comprising the HMO and a blister of comprising the formulation tablets. Or alternatively other packed forms are used. Afterwards adding a package leaflet to the filled kit case. Therefore, the present invention relates to a kit (K12), which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8), (K9), (K10) or (K11), wherein the kit comprises an outer packaging.
That outer packing can be any kind of usually used material or combination of material (paper, plastic, glass, etc).
The outer packing can be useful for the protection of the kit and/or nice appearance of the kit. For the purpose of storing the kit such an outer packing may also be useful.
The kit according to the present invention can also comprise instructions for use.
Therefore, the present invention relates to a kit (K13), which is the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8), (K9), (K10), (K11) or (K12), wherein the kit instructions for use.
The instructions may be in the form of a leaflet of may be printed on the kit or on the outer packing.
Furthermore, the present invention relates to a method of treatment, prevention or prophylaxis of norovirus infections using the kit (K), (K1), (K2), (K2’), (K3), (K4), (K5), (K6), (K7), (K8), (K9), (K10), (K11) or (K12).
The following examples serve to illustrate specific embodiments of the invention claimed herein. All percentages are given in relation to the weight and all the temperatures are given in degree Celsius.
- w -
Examples
Example 1 :
Step 1 : production of tablets comprising formulation of invention and filling in blister
Step 2: production of sachets, comprising HMO
Step 3: production of kit by filling an empty kit case with 10 sachets of step 2 and a blister of step 1 comprising 10 tablets
Step 4: adding a package leaflet to the filled kit case of step 3

Claims

Claims A kit comprising:
(a) a first container comprising a solid formulation consisting of
(i) a solid core, which comprises at least one fat-soluble vitamin, and
(ii) an inner coating comprising at least one fermentable biopolymer, which is crosslinked, and
(iii) an outer coating which is resistant to stomach conditions and releasing in the small intestine, b) a second container comprising at least one human milk oligosaccharide. Kit according to claim 1 wherein the solid core of the solid formulation in the first container comprises at least one fat soluble vitamin chosen from the group consisting of vitamin A, D, E and K. Kit according to claim 1 wherein the solid core of the solid formulation in the first container comprises at least one fat soluble vitamin is vitamin A and/or a derivative of vitamin A (such as vitamin A palmitate or vitamin A acetate). Kit according to anyone of the preceding claims, wherein the material of the inner coating of the solid formulation in the first container is chosen from group consisting of alginate, chitosan, pectin, cyclodextrin as well as other gums. Kit according to anyone of the preceding claims, wherein the thickness of the inner coating layer of the solid formulation in the first container is 5pm - 10pm. Kit according to anyone of the preceding claims, wherein the inner coating layer of the solid formulation in the first container is crosslinked with at least one crosslinking agent (preferably with Zn, Mg and/or Ca ions). Kit according to anyone of the preceding claims, wherein the material of the outer coating of the solid formulation in the first container is chosen from group consisting of shellac, methacrylate copolymers and fats. Kit according to anyone of the preceding claims, wherein the solid core of the delivery system of the solid formulation in the first container is 50 - 85 wt- %, preferably 55 - 75 wt-%, based on the total weight of the delivery system. Kit according to anyone of the preceding claims, wherein the inner coating of the delivery system in the first container is 1 - 20 wt- %, preferably 5 - 15 wt-%, based on the total weight of the delivery system. Kit according to anyone of the preceding claims, wherein the outer coating of the delivery system in the first container is 1 - 30 wt- %, preferably 15 - 30 wt-%, based on the total weight of the delivery system Kit according to anyone of the preceding claims, wherein the second container comprises at least one HMO selected from the group consisting of 2 '-fucosy I lactose (2' FL), lacto-N-neotetraose (LNnT) and 3-fucosyllactose (3FL). Kit according to anyone of the preceding claims, wherein the kit comprises an outer packaging. Kit according to anyone of the preceding claims, wherein the kit instructions for use. Kit according to anyone of the preceding claims for use in the of treatment, prevention or prophylaxis of norovirus infection. Use of a solid formulation for manufacturing a kit that comprises at least one fatsoluble vitamin and at least one human milk oligosaccharide, wherein said solid formulation consists of
(i) a solid core, which comprises at least one fat-soluble vitamin, and (ii) an inner coating comprising at least one fermentable biopolymer, which is crosslinked, and
(iii) an outer coating which is resistant to stomach conditions and re-leasing in the small intestine.
PCT/EP2021/079455 2020-10-29 2021-10-25 Specific kit comprising a specific fat soluble vitamin formulation and a formulation of specific human milk oligosaccharides WO2022090112A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP20204515 2020-10-29
EP20204515.9 2020-10-29

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2887925A1 (en) * 2012-08-27 2015-07-01 Evonik Industries AG Gastric resistant pharmaceutical or nutraceutical composition with resistance against the influence of ethanol
US20200069709A1 (en) * 2017-03-01 2020-03-05 Glycom A/S Synthetic composition for microbiota modulation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2887925A1 (en) * 2012-08-27 2015-07-01 Evonik Industries AG Gastric resistant pharmaceutical or nutraceutical composition with resistance against the influence of ethanol
US20200069709A1 (en) * 2017-03-01 2020-03-05 Glycom A/S Synthetic composition for microbiota modulation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KOROMYSLOVA ANNA ET AL: "Human norovirus inhibition by a human milk oligosaccharide", VIROLOGY, ELSEVIER, AMSTERDAM, NL, vol. 508, 12 May 2017 (2017-05-12), pages 81 - 89, XP085068377, ISSN: 0042-6822, DOI: 10.1016/J.VIROL.2017.04.032 *

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