WO2009066138A2 - Stabilisation d'une injection d'un complexe de vitamines b et de chlorhydrate de lidocaïne - Google Patents

Stabilisation d'une injection d'un complexe de vitamines b et de chlorhydrate de lidocaïne Download PDF

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Publication number
WO2009066138A2
WO2009066138A2 PCT/IB2008/002626 IB2008002626W WO2009066138A2 WO 2009066138 A2 WO2009066138 A2 WO 2009066138A2 IB 2008002626 W IB2008002626 W IB 2008002626W WO 2009066138 A2 WO2009066138 A2 WO 2009066138A2
Authority
WO
WIPO (PCT)
Prior art keywords
composition
vitamin
stabilizer
lidocaine
range
Prior art date
Application number
PCT/IB2008/002626
Other languages
English (en)
Other versions
WO2009066138A3 (fr
Inventor
Sateesh Kumar Chauhan
Surender Kumar Kamal
Deepak Bahri
Original Assignee
Promed Research Centre
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 Promed Research Centre filed Critical Promed Research Centre
Publication of WO2009066138A2 publication Critical patent/WO2009066138A2/fr
Publication of WO2009066138A3 publication Critical patent/WO2009066138A3/fr

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Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • the present invention relates to the field of formulations and more particularly relates to a stable composition comprising multivitamins for human and veterinary administration.
  • Multivitamin formulations are one of the most common and largely used products - throughout the world and making the formulations more stable will have tremendous industrial applicability.
  • Vitamin B-complex preparation comprises mixture of two or more of solid or crystalline vitamins that are necessary for energy metabolism. These preparations are commonly marketed as solid vitamin products, usually in the form of tablets or as gelatin capsules and parenteral vitamin products, such as intra-muscular injections.
  • vitamin Bi thiamine
  • the potency of the product also decreases markedly with the passage of time. This loss in potency has been shown by chemical and animal tests to result from the actual chemical destruction of the vitamin rather than to any masking or similar effect exerted by other vitamins contained in the preparation.
  • components of vitamin B complex such as Thiamine, riboflavin and cyanacobalamin are light sensitive and prone to oxidation. The solution of these components in combination is not stable if not protected with stabilizers.
  • Vitamins and nutrients are generally sensitive to the effects of temperature, oxygen, and light; a slight change in the molecular structure of a nutrient can render it biologically ineffective.
  • the following vitamins are known to be specifically vulnerable to degradation by UV light: Vitamin A, B 2 (riboflavin), Be, B 12 , and folic acid. Light also accelerates the destructive interaction between vitamins
  • the degradation may be inhibited by adding various stabilizing agents such as sodium formaldehyde sulphoxylate, propyl gallate, glycine, butylated ' hydroxyanisole, butylated hydroxytoulene in concentration dependent manner.
  • stabilizing agents such as sodium formaldehyde sulphoxylate, propyl gallate, glycine, butylated ' hydroxyanisole, butylated hydroxytoulene in concentration dependent manner.
  • US patent 5,173,4808 discloses a method for stabilization of an injectable aqueous composition comprising folic acid by adding stabilizing agents such as tromethamine and monothioglycerol. Considering the shortcomings of the prior art, there is a need to provide a stabilized composition comprising vitamins especially vitamin B.
  • the principle objective of the present invention is to provide a composition of vitamin B complex. Another objective of the present invention is to enhance the stability of vitamin B complex composition and increase its shelf life.
  • the present invention provides a stable composition
  • a stable composition comprising vitamin B l (thiamin), vitamin B6 (pyridoxine), vitamin B 12 (cyanocobalamine), a local anesthetic agent together with one or more stabilizers.
  • the present invention provides a stable Vitamin B complex composition
  • a stable Vitamin B complex composition comprising vitamin B 1 , vitamin B 6 , Vitamin B 12 , a local anesthetic agent in combination with at least two stabilizers.
  • the local anesthetic agent may be selected from a group comprising of anesthetics such as like benzociane, chloroprocaine, cocaine, procaine, tetracaine; or amides like bupivacaine, levobupivaciane, lidocaine, ropivacaine, articaine, trimecaine, prilocaine.
  • anesthetics such as like benzociane, chloroprocaine, cocaine, procaine, tetracaine; or amides like bupivacaine, levobupivaciane, lidocaine, ropivacaine, articaine, trimecaine, prilocaine.
  • the local anesthetic agent is lidocaine or its salt.
  • the amount of the anaesthetic may be in range of lOmg to 50 mg per ml.
  • the stabilizers are selected from the group comprising a chelating agent, organic acid and cyanoferrate and more preferably stabilizers are ethylene diamine tetra acetic acid, malic acid and potassium ferrocynide.
  • the amount of stabilizer may be in a range of 0.005-1.0%, 0.05-5% or 0.005-1.0%. More preferably the composition ethylene diamine tetra acetic acid (EDTA) is 0.10 %, malic acid is 0.5% and potassium ferrocynide is 0.1%.
  • EDTA ethylene diamine tetra acetic acid
  • the composition of the invention exhibits synergistic effect in that the vitamins in combination with the anesthetic agent and the stabilizers are synergistic. As shown in Table 1, the combination of EDTA with potassium hexaferrocyanide exhibited the best synergistic effect. The composition exhibits both physical stability and prevents the degradation of Vitamin B 12. The combination containing malic acid, potassium hexaferrocyanide and EDTA showed synergistic effect, better than the combination of two.
  • the samples were kept in a stability chamber at 4O 0 C and tested after 4 weeks of exposure. The results were compared with initial sample.
  • the comparative formulations are provided in table-1.
  • the product without any stabilizer is not stable as the sample shows turbidity.
  • the product formulated individually with/stabilizers such as Potassium hexa ferrocyanide, disodium EDTA and malic acid showed physical instability and degradation of vitamin B 12, respectively.
  • the composition containing combinations of malic acid with potassium ferrocyanide and disodium EDTA with Malic acids were also ineffective, rendering the composition physically unstable or unable to prevent degradation of vitamin B 12.
  • the composition may be used in the symptomatic treatment of nervous diseases of different origins such as neuritis, neuralgia, polyneuropathy, myalgia, radicular syndromes, retrobulbar neuritis, herpes zoster varicellosus, paresis of facial nerve; and in systemic nervous diseases caused by vitamin Bl and B6 deficiency.
  • nervous diseases of different origins such as neuritis, neuralgia, polyneuropathy, myalgia, radicular syndromes, retrobulbar neuritis, herpes zoster varicellosus, paresis of facial nerve; and in systemic nervous diseases caused by vitamin Bl and B6 deficiency.
  • the above table describes the various trials carried out by using different combination of stabilizers.
  • the stabilizers present in the various formulations are
  • composition of the present invention may be prepared by a process comprising
  • the invention provides a composition which is stable. Hence as in the prior art, there is no need to add "overages" to the compositions thus saving substantial costs in manufacture.
  • composition is stable and thus has an extended shelf life. Hence the storage and transportation of the compositions are made simple and easy.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Emergency Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une composition parentérale stable d'un complexe de vitamines B et de chlorhydrate de lidocaïne qui est stabilisée par une combinaison synergétique de stabilisants tels que l'acide DL-malique, l'édétate disodique et l'hexacyanoferrate de potassium III ; et le procédé s'y rapportant.
PCT/IB2008/002626 2007-11-22 2008-10-06 Stabilisation d'une injection d'un complexe de vitamines b et de chlorhydrate de lidocaïne WO2009066138A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2441DE2007 2007-11-22
IN2441/DEL/2007 2007-11-22

Publications (2)

Publication Number Publication Date
WO2009066138A2 true WO2009066138A2 (fr) 2009-05-28
WO2009066138A3 WO2009066138A3 (fr) 2009-07-09

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2008/002626 WO2009066138A2 (fr) 2007-11-22 2008-10-06 Stabilisation d'une injection d'un complexe de vitamines b et de chlorhydrate de lidocaïne

Country Status (1)

Country Link
WO (1) WO2009066138A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011145914A1 (fr) * 2010-05-19 2011-11-24 Alejandra Zepeda Flores Lidocaïne utilisée en tant qu'agent de transformation et de production de complexes pharmaceutiques transformés appliqués en nanodoses au moyen d'implants par injection utilisés en tant que dispositifs à libération lente

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002034199A2 (fr) * 2000-10-24 2002-05-02 Ivan Dimitrov Hristov Medicament destine au traitement de la sclerose en plaques
WO2002045705A2 (fr) * 2000-12-08 2002-06-13 Pieter Theo Ernst Traitement therapeutique

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2225707C1 (ru) * 2003-03-04 2004-03-20 Закрытое акционерное общество "Брынцалов-А" Фармацевтическая композиция, обладающая анальгезирующим, улучшающим кровоснабжение, стимулирующим регенерацию нервной ткани и противоаллергическим действием

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002034199A2 (fr) * 2000-10-24 2002-05-02 Ivan Dimitrov Hristov Medicament destine au traitement de la sclerose en plaques
WO2002045705A2 (fr) * 2000-12-08 2002-06-13 Pieter Theo Ernst Traitement therapeutique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Derwent Publications Ltd., London, GB; AN 2004-326179 & RU 2 225 707 C1 (BRYNTSALOV A STOCK CO) 20 March 2004 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011145914A1 (fr) * 2010-05-19 2011-11-24 Alejandra Zepeda Flores Lidocaïne utilisée en tant qu'agent de transformation et de production de complexes pharmaceutiques transformés appliqués en nanodoses au moyen d'implants par injection utilisés en tant que dispositifs à libération lente

Also Published As

Publication number Publication date
WO2009066138A3 (fr) 2009-07-09

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