Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
• • 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
  • A61K31/16—Amides, e.g. hydroxamic acids
  • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
• • 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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
• • 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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
  • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
  • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• • 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
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
  • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
  • A61K31/52—Purines, e.g. adenine
  • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• • 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
  • A61K31/7135—Compounds containing heavy metals
  • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/24—Heavy metals; Compounds thereof
  • A61K33/30—Zinc; Compounds thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/02—Inorganic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
  • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
  • A61K47/38—Cellulose; Derivatives thereof
• • 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
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
• • 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
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0043—Nose
• • 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
  • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7007—Drug-containing films, membranes or sheets
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/04—Antipruritics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/02—Nutrients, e.g. vitamins, minerals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/08—Antiallergic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• the invention relates to a vitamin preparation, in particular in gel form for application to the skin, which contains a physiologically and / or therapeutically effective amount of vitamin B12.
• Vitamin B12 belongs to the group of cobalamins and is an essential vitamin that can not be synthesized in the human body. Human needs must therefore be met through food. Cobalamines are particularly present in animal feed in sufficient quantities. The origin is always bacterial.
• vitamin B12 is understood to mean cyanocobalamin. Other forms are z. As the aquocobalamin, hydroxycobalamin and methylcobalamin, which is usually found in the body cells.
• the effective coenzyme B12 is the 5'-deoxyadenosylcobalamin. In the body the active forms methylcobalamin and adenosylcobalamin are formed from the other forms.
• vitamin B1 2 is understood in particular to mean the cyanocobalamin conventionally designated as vitamin B12, but also the other precursor forms of coenzyme B12, as mentioned above.
• Vitamin B12 has been shown to be very effective in the treatment of a variety of skin conditions. It is in ointment form in a series of dermatoses, but also applied to atopic eczema.
• the ointment base used is a synthetic or vegetable oil or fat, in particular avocado oil.
• WO 2014/01 6277 A2 discloses a vitamin preparation in which vitamin B12 can be administered transdermally with the aid of polysorbates as entrainer.
• the object of the invention is therefore to provide a vitamin preparation which is suitable for efficiently introducing vitamin B12 into the upper skin layers in order to achieve a lasting effect there.
• vitamin preparation of the type mentioned in the introduction, which contains a physiologically and / or therapeutically effective amount of vitamin B12, a poloxamer and conventional carrier materials for forming a carrier matrix.
• Poloxamers are block copolymers of ethylene oxide and propylene oxide, in which a propylene oxide block is enclosed on both sides by ethylene oxide blocks. Poloxamers are surface-active, since the polypropylene oxide part is rather hydrophobic, whereas the two polyethylene oxide parts are hydrophilic. Accordingly, they can be classified as nonionic surfactants, which are often used for dispersion and emulsification in the chemical-technical industry application. Because of their amphiphilic properties, they are widely used as carrier materials in cosmetic and pharmaceutical products. Depending on the degree of ethoxylation, poloxamers are liquid or solid.
• Poloxamers are available with different molecular weights and alkylene oxide distributions. The proportion of ethylene oxide units is responsible for the hydrophilicity. Common types used in the pharmaceutical and Poloxamer 188, 237, 338 and 407 are used in the cosmetic industry. The final digit number multiplied by 10 stands for the percentage of ethylene oxide. Poloxamer 407 has an ethylene oxide content of 70% by weight. Surprisingly, it has now been found that because of their amphiphilic properties, poloxamers are not only suitable as carriers for a very wide variety of substances, but, above all, are also able to administer active substances transdermally. They act as entrainer, which transport the corresponding active ingredient, in particular vitamin B12 or its corresponding precursor, through the skin or mucous membrane.
• vitamin B12 In addition to vitamin B12, other active ingredients of poloxamers can be transported through the skin or mucous membrane. This is especially true for phytochemicals such as nicotine, caffeine, simple and polyphenols (for example epigallocatechin gallate) and flavonoids. Simple phenols and polyphenols are known for their anti-inflammatory effects.
• the drag effect in transdermal preparations with vitamin B12 can be further improved if, in addition to a poloxamer, a polysorbate, in particular polysorbate 20 (Tween®), is also present.
• a polysorbate in particular polysorbate 20 (Tween®)
• Poloxamers preferred according to the invention are the poloxamers 188 and 407, polaxomers with 80 or 70% by weight. Glycol content.
• Suitable polysorbates are the customary commercially available products. These are each polyethoxylated sorbitan fatty acid esters of various fatty acids, such as lauric acid, palmitic acid, stearic acid, oleic acid or isostearic acid. Preferred polysorbate is Polysorbate 20, which is traded under the name Tween®. The proportion of polysorbate in a preparation according to the invention may be 20 to 100 mg per 100 g of the Preparation is and is in particular about 40 mg per 100 g of the preparation.
• the vitamin preparation according to the invention contains customary carrier materials for forming the carrier matrix, in particular a gel matrix.
• carrier materials for forming the carrier matrix, in particular a gel matrix.
• Such substances are, for example, glycerol, hydroxyethyl cellulose, urea and demineralized water.
• citric acid and / or sodium hydroxide solution may be present, which have proven to be extremely compatible with the body.
• Other acids and bases can also be used.
• the preparation can also be present as a lotion, cream, ointment, spray, tincture or as a shampoo.
• the vitamin preparation according to the invention contains vitamin B12 or another form of cobalamin in an amount of 40 to 100 mg, in particular in an amount of 70 mg per 100 g of the preparation.
• the poloxamer is contained in an amount of 20 to 500 mg per 100 g of the preparation, especially in an amount of 100 mg.
• hydroxyethyl cellulose 400 is used in an amount of 1000 mg to 5000 mg per 100 g of the preparation.
• Further constituents may be glycerol in an amount of 1000 mg to 5000 mg per 100 g and urea in an amount of 2000 mg to 7000 mg per 100 g.
• the preparation may further contain an antiseptic, such as polyhexanide.
• an antiseptic such as polyhexanide.
• polyhexanide This is added in the form of a commercially available solution concentrate (20% w / v) and is preferably contained in an amount of 100 to 500 mg of concentrate per 100 g.
• the addition of polyhexanide is particularly helpful in inflamed and inflammatory skin diseases in which it comes to infestation with microorganisms.
• Polyhexanide is an antiseptic based on polyhexamethylene biguanide (PHMB).
• the vitamin preparation may contain other beneficial for the treatment of the skin active ingredients.
• dexpanthenol for example a vitamin precursor is. It is converted in the body to pantothenic acid, which is a vitamin from the group of B vitamins (vitamin B5).
• Dexpanthenol is included, for example, in an amount of 1000 mg to 10000 mg per 100 g in the preparation. Further constituents are if necessary polyethylene glycol 400 as well as, thus antioxidant, sodium ascorbate.
• the vitamin preparation according to the invention is preferably composed as follows:
• the vitamin preparation according to the invention can be applied as a gel to the skin, but also be present in gel form on or in a plaster or pad, which is then applied to the skin. It can also be applied as a spray and applied as a tincture, for example in the form of nasal spray or eye drops.
• a good effect has been found in other types of irritation of the skin and mucous membranes, especially in allergic irritants, such as pollen allergies, house dust allergy and allergic reactions to insect bites.
• the invention is explained in more detail by the following examples:
• a vitamin preparation in gel form was prepared from the following ingredients: 1. Vitamin B12 (cyanocobalamin) 70 mg
• Hydroxyethylcellulose400 up to 5000 mg, depending on the desired consistency
• the ingredients are mixed with gentle warming and stirred into a gel.
• Example 1 The preparation of Example 1 is supplemented with 5000 g of dexpanthenol and 2000 mg of PEG400.
• taurine As further constituents, about 300 mg of taurine, 25 mg of caffeine, 1000 mg of lysine, 500 g of zinc sulfate and / or 500 mg of creatine can be mixed.
• Sodium ascorbate is mixed in as far as antioxidant is needed.
• Purified pigskin is divided and coated with a 28 mg Co / I vitamin B12 solution. After 1 h, the skin is rinsed, dried, crushed and extracted with aqueous hydrochloric acid in an ultrasonic bath.
• the entrainer used was 40 mg Tween®, 100 mg Poloxamer 180 and a combination of 100 mg Poloxamer + 40 mg Tween®, each to 100 ml of the test solution. The following values were obtained for the absorption of cobalt into the skin:
• the pure vitamin B12 solution (without entrainer) gave a Co uptake of only 3.0 mg Co / kg.

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• Health & Medical Sciences (AREA)
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• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
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• Public Health (AREA)
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• Inorganic Chemistry (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Molecular Biology (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Dermatology (AREA)
• Otolaryngology (AREA)
• Biochemistry (AREA)
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• Rheumatology (AREA)
• Pain & Pain Management (AREA)
• Obesity (AREA)
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• Hematology (AREA)
• Pulmonology (AREA)
• Diabetes (AREA)
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• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Cosmetics (AREA)

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• 2016
  • 2016-04-22 DE DE102016107563.9A patent/DE102016107563A1/de active Pending
• 2017
  • 2017-04-21 EP EP17724319.3A patent/EP3445333A1/de active Pending
  • 2017-04-21 JP JP2018555119A patent/JP7344641B2/ja active Active
  • 2017-04-21 RU RU2018140968A patent/RU2018140968A/ru unknown
  • 2017-04-21 WO PCT/EP2017/059496 patent/WO2017182619A1/de not_active Ceased
  • 2017-04-21 CN CN201780025027.8A patent/CN109195586A/zh active Pending
  • 2017-04-21 US US16/094,659 patent/US20190111139A1/en not_active Abandoned

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