WO2011013138A1 - Formulations multi-vitaminiques stables - Google Patents

Formulations multi-vitaminiques stables Download PDF

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Publication number
WO2011013138A1
WO2011013138A1 PCT/IN2009/000731 IN2009000731W WO2011013138A1 WO 2011013138 A1 WO2011013138 A1 WO 2011013138A1 IN 2009000731 W IN2009000731 W IN 2009000731W WO 2011013138 A1 WO2011013138 A1 WO 2011013138A1
Authority
WO
WIPO (PCT)
Prior art keywords
vitamin
solution
parenteral
multivitamin
solubilizing
Prior art date
Application number
PCT/IN2009/000731
Other languages
English (en)
Inventor
Debjani Singh
Purushothama Narasyappa
Srirama Sarveswara Rao Mandavilli
Mohan Mailatur Sivaraman
Original Assignee
Strides Arcolab Limited
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 Strides Arcolab Limited filed Critical Strides Arcolab Limited
Publication of WO2011013138A1 publication Critical patent/WO2011013138A1/fr

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Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
    • 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
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • 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
    • A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions

Definitions

  • the invention relates to a lyophilized composition of multivitamins which is filled in a single vial for parenteral administration.
  • vitamins are broadly classified in to two categories. Water soluble and fat soluble vitamins. Vitamin C and vitamins of B- Complex fall under water soluble category and other vitamins fall under Fat soluble category.
  • Folic acid deficiency may result in megaloblastic anemia after as little as 4 weeks without multivitamin supplementation.
  • Folic acid is a cofactor in numerous metabolic pathways, especially those of amino acid and nucleotide metabolism, and is necessary for DNA synthesis.
  • Folic acid deficiency has been shown to be related to certain birth defects, especially anencephaly.
  • Niacin (nicotinic acid, vitamin B3) deficiency can result in pellagra, which is characterized by dermatitis, diarrhea, and dementia.
  • Niacin is an important component of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), cofactors of dehydrogenase enzymes involved in many important metabolic pathways.
  • NAD nicotinamide adenine dinucleotide
  • NADP nicotinamide adenine dinucleotide phosphate
  • a deficiency of thiamine can develop quite rapidly. This is often manifested with symptoms characteristic of peripheral neuritis, known as “dry beriberi.” In severe cases, cardiac dysfunction from high output failure can occur, and is referred to as “wet beriberi.” The occurrence of severe, sometimes fatal, clinical thiamine deficiency in patients receiving TPN" demonstrates the need to insure that all parenteral nutrition contain thiamine in adequate quantities. Thiamine may be deficient in apparently well nourished alcoholics.” Immediate, appropriate, and daily multivitamin supplementation is especially important in these patients.
  • Riboflavin (vitamin B2) deficiency is characterized by stomatitis, glossitis, and seborrheic dermatitis. Riboflavin is an important component of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), cofactors of enzymes involved in biological oxidation reduction reactions, including those involved in glucose oxidation, amino acid deamination, and free fatty acid breakdown. Vitamin B6 (pyridoxine) is required for amino acid metabolism and protein synthesis. Transamination and decarboxylation are essential biochemical processes that require vitamin B6 or its metabolites.' Metabolites of vitamin B6 are involved in the biosynthesis of porphyrins and heme.
  • Deficiency of pyridoxine produces glossitis and stomatitis. Peripheral neuritis and seizures can also occur.
  • Deficiency of vitamin B 12 (cyanocobalamin) can result in pernicious anemia. Vitamin B 12 is essential for thymidylate synthesis and, therefore, for DNA synthesis. Any abnormality of the distal ileum, where its metabolic receptor is found, can reduce vitamin B 12 absorption.
  • Pantothenic acid deficiency includes nausea, vomiting, headache, muscle cramps, fatigue, and paresthesia of the hands and feet.
  • Pantothenic acid is used as a building block in the synthesis of coenzyme A (essential for glucose, protein, and fat metabolism) and acyl carrier protein (essential for fatty acid synthesis).Biotin. Biotin deficiency may result in dermatitis, as well as in paresthesia. Biotin is an important cofactor for many enzymes involved in carbohydrate, fat, and protein metabolism.
  • Fat soluble Vitamin A has numerous functions. Besides its well known role in vision, it is important for cellular differentiation and for the functioning of the immune systems. Vitamin A has effects on cell mediated immunity and lymphoproliferation in vitro. A correlation exists between vitamin A deficiency and an increased susceptibility to infections. Vitamin A may aiso reverse the inhibitory effect of corticosteroids on the healing of intestinal anastomoses.
  • US Patent No. 3,914,419 teaches an injectable liquid composition of multivitamins in a two chambered one unit consecutively administrable package.
  • the invention also discloses stable aqueous multivitamin preparation in two phases at two different pH. Each incompatible phase is stored in two different compartments of a single hypodermic syringe.
  • the composition however does not include Vitamin K.
  • US Patent No. 4,740,373 teaches stable aqueous multivitamin/trace elements preparation for parenteral administration.
  • the said patent discloses the use of unsaturated organic acids prevent the rapid inter-reaction between vitamins and trace elements and act as potential stabilizers.
  • the incompatibility between the different vitamins is not dealt and the composition is filled in two compartment one unit vial or syringe.
  • US Patent No. 5,770,233 teaches a container with two compartments each filled with infusion liquids. Further one of the compartments in the container comprises of vitamin C, vitamin Bl, vitamin B2, vitamin A, vitamin D, vitamin E, vitamin K in fat emulsion and sugar; the second compartment comprises of amino acid, electrolyte, vitamin B6, vitamin B 12 and folic acid.
  • vitamins are usually unstable and a certain combination of vitamins can cause decomposition of one of the vitamins or can make the liquid turbid.
  • US Patent No. 6,129,925 which is a continuation of US5,770,233 recites an infusion preparation comprising amino acid, electrolytes, fat emulsion, sugar and vitamins. The preparation is filled in a two compartment container to avoid any mixing of the content in each.
  • WO Publication No. 98/08522 discloses a composition of multivitamins and other essential elements wherein the actives are mixed in dry state and put into a suitable unit dose delivery device such as a capsule, sachet or other unit dose which does not involve significant compaction.
  • a suitable unit dose delivery device such as a capsule, sachet or other unit dose which does not involve significant compaction.
  • This application discloses a nutrient composition targeted to achieve better autonomic balance and enhanced performance in the patient.
  • Another objective of the present invention is to provide a product under proper dilution that would contribute intake of necessary vitamins including vitamin K for maintaining the body's normal resistance and repair processes (not only as daily maintenance dose but also in situations like surgery, extensive burns, trauma, fractures and severe infections).
  • Another objective of the present invention is to provide a stable lyophilized formulation of 13 multivitamins and process for preparation thereof.
  • the present invention provides a parenteral formulation comprising combination of water soluble and oil soluble vitamins in physiologic micellar system containing soybean lecithin, glycocholic acid and glycine as adjutants to produce a stable lyophilized product which is filled in a unitary container closure system.
  • the present invention provides a stable lyophilized parenteral formulation comprising 13 vitamins selected from the group of water soluble and fat soluble vitamins.
  • the said lyophilized formulation is meant for both adult as well as pediatric population groups.
  • the summary of process for manufacturing a stable parenteral multivitamin lyophilized formulation comprises of following steps:
  • the detailed process for preparing the lyophilized parenteral formulation comprises of following steps:.
  • solubilizing fat soluble vitamins involving following steps: a) solubilizing of soy lecithin;
  • folic acid (Vitamin B9) and Dexpanthenol (Vitamin B5) are added after Step III at an optimal pH but not restricted to 5.5 ⁇ 0.1.

Abstract

La présente invention concerne une formulation multi-vitaminique parentérale lyophilisée stable comprenant des combinaisons de 13 vitamines choisies parmi les vitamines hydrosolubles et les vitamines liposolubles, dans un système micellaire physiologique, convenant au conditionnement en emballage unitaire de type récipient-fermeture.
PCT/IN2009/000731 2009-07-29 2009-12-22 Formulations multi-vitaminiques stables WO2011013138A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1784CH2009 2009-07-29
IN1784/CHE/2009 2009-07-29

Publications (1)

Publication Number Publication Date
WO2011013138A1 true WO2011013138A1 (fr) 2011-02-03

Family

ID=43528842

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2009/000731 WO2011013138A1 (fr) 2009-07-29 2009-12-22 Formulations multi-vitaminiques stables

Country Status (1)

Country Link
WO (1) WO2011013138A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011141113A3 (fr) * 2010-04-15 2012-01-05 Fresenius Medical Care Deutschland Gmbh Combinaison de vitamine k et de nicotinamide
WO2019081435A1 (fr) * 2017-10-25 2019-05-02 Fresenius Kabi Deutschland Gmbh Émulsion multi-vitamine lyophilisée tout-en-un pour application parentérale
WO2019113543A1 (fr) * 2017-12-07 2019-06-13 Reven, Llc Compositions et méthodes pour le traitement d'affections métaboliques
CN111329839A (zh) * 2020-04-02 2020-06-26 北京鑫兰医药科技有限公司 一种复合维生素冻干制剂及其制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0247616A2 (fr) * 1986-05-27 1987-12-02 Rorer International (Overseas) Inc. Stabilisation de formulations multivitamines et éléments en trace
US5376646A (en) * 1990-01-24 1994-12-27 Hoffmann-La Roche Inc. Topical preparations containing the salt of a cholanic acid and a lipid

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0247616A2 (fr) * 1986-05-27 1987-12-02 Rorer International (Overseas) Inc. Stabilisation de formulations multivitamines et éléments en trace
US5376646A (en) * 1990-01-24 1994-12-27 Hoffmann-La Roche Inc. Topical preparations containing the salt of a cholanic acid and a lipid

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TEVA MEDICAL MARKETING WEB PUBLICATION: "Cernevit Powder for Solution for Intravenous Administration", CERNEVIT PHYSICIANS' PRESCRIBING INFORMATION, 2003, pages 1 - 4 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011141113A3 (fr) * 2010-04-15 2012-01-05 Fresenius Medical Care Deutschland Gmbh Combinaison de vitamine k et de nicotinamide
WO2019081435A1 (fr) * 2017-10-25 2019-05-02 Fresenius Kabi Deutschland Gmbh Émulsion multi-vitamine lyophilisée tout-en-un pour application parentérale
CN110573142A (zh) * 2017-10-25 2019-12-13 费森尤斯卡比德国有限公司 用于胃肠外应用的多合一冻干复合维生素乳剂
CN110573142B (zh) * 2017-10-25 2024-01-16 费森尤斯卡比德国有限公司 用于胃肠外应用的多合一冻干复合维生素乳剂
US11975102B2 (en) * 2017-10-25 2024-05-07 Fresenius Kabi Deutschland Gmbh All-in-one lyophilized multivitamin emulsion for parenteral application
WO2019113543A1 (fr) * 2017-12-07 2019-06-13 Reven, Llc Compositions et méthodes pour le traitement d'affections métaboliques
CN111565709A (zh) * 2017-12-07 2020-08-21 雷文知识产权控股有限公司 治疗代谢病症的组合物和方法
US11344529B2 (en) 2017-12-07 2022-05-31 Reven Ip Holdco Llc Compositions and methods for the treatment of metabolic conditions
CN111329839A (zh) * 2020-04-02 2020-06-26 北京鑫兰医药科技有限公司 一种复合维生素冻干制剂及其制备方法

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