WO2006091180A2 - Systemes vecteurs du medicament multiparticulaire fucoidane - Google Patents

Systemes vecteurs du medicament multiparticulaire fucoidane Download PDF

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Publication number
WO2006091180A2
WO2006091180A2 PCT/TR2005/000015 TR2005000015W WO2006091180A2 WO 2006091180 A2 WO2006091180 A2 WO 2006091180A2 TR 2005000015 W TR2005000015 W TR 2005000015W WO 2006091180 A2 WO2006091180 A2 WO 2006091180A2
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WO
WIPO (PCT)
Prior art keywords
chitosan
fucoidan
solution
drug carrier
value
Prior art date
Application number
PCT/TR2005/000015
Other languages
English (en)
Other versions
WO2006091180A3 (fr
Inventor
Ali Demir Sezer
Original Assignee
Ali Demir Sezer
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 Ali Demir Sezer filed Critical Ali Demir Sezer
Priority to PCT/TR2005/000015 priority Critical patent/WO2006091180A2/fr
Publication of WO2006091180A2 publication Critical patent/WO2006091180A2/fr
Publication of WO2006091180A3 publication Critical patent/WO2006091180A3/fr

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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
    • A61K9/14—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
    • 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
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • 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

Definitions

  • This invention is related with the preparation of multiparticulates: a drug carrier system to inject the drugs into human body.
  • Multiparticulate systems are defined as spherules, which according to the preparation technique are drug encapsulated in polymer/s or dispensed in the polymer system and carried within the body and the sizes vary between nanometer to millimeter.
  • polymers are used. Polymers, in its simplest definition, are a high amount of the same or various atoms with chemical bounds, bounded together more or less regularly to form a long chained and thus high molecular weight compounds. These structures are synthetic, semi-synthetic or natural and all are used for the preparation of multiparticulate systems.
  • Multiparticulate systems are made of compounds embodying complexes formed by polymer/s and pharmaceutically active agents.
  • Onto other polycationic polymers chitosan and its salt or a derivative, which mostly has a polysaccharide structure, is preferred as the polycationic polymers for use.
  • a carrier preferably pharmaceutically acceptable within the current status of the technique; like oligonucleotide; a negative loaded pharmacologically effective agent and with a polycationic polymer, like chitosan or chitosan salt or a derivative
  • the drug is encapsulated and injected into the body and controlled release is obtained and the agent is protected from exterior effects.
  • a polycationic polymer like chitosan or chitosan salt or a derivative
  • WO 03/030941 discloses the controlled release drug compounds, that includes polycationic polymers like chitosan and negative loaded pharmaceutically active substances.
  • Chinese patent numbered 1293952 discloses the preparation of microparticulates by mixture of chitosan and fibroin and the use of this microparticulate in controlled release of drugs.
  • the object of this invention is not only the preparation of fucoidan multiparticulate system without the need of organic solvent and excipients as catalysts, but also to accomplish that in a very short time and with a very simple preparation procedure.
  • the fucoidan multiparticulate systems with its being used as a drug carrier system for the first time and without the need for organic solvents and any excipients as catalysts, and its very short and simple preparation period is an improvement regards to multiparticulate systems.
  • Chitosan as a natural polymer which has a biological solubility, is very important as a cationic polymer that takes part in the structures of controlled release systems in the injection of high molecular weight substances such as protein-peptides to human body.
  • the primary basis of this system is made up of fucoidan, a polysaccharide; which is obtained from algae and due to the sulfates in its structure shows an anionic character.
  • Fucoidan multiparticulate systems are prepared via the combination of fucoidan, which shows a strong anionic character and chitosan another polysaccharide, which shows cationic character.
  • chitosan which has a molecular weight between 10 to 1500 kD is solved in acid solvent and according to the size of the multiparticulates preferred to be obtained, mixed rather in a homogenizer or a low RPM stirrer.
  • the fucoidan solution that is prepared with a suitable amount of bi-distilled or distilled water and has a pH value 5.0 to 7.0 is slowly added onto chitosan, which is being stirred and has a pH value 1.0 to 7.0.
  • the mixture ratio of chitosan and fucoidan solutions is 0.1 : 5.0.
  • the solution that includes 0.1% to 4.0% fucoidan and 0.1% to 5.0% chitosan is stirred in the homogenizer or the stirrer until the particles are formed. Then particles are centrifuged so that they are free of wastes, then washed and eliminated after they are lyophilized.
  • BSA Bovine Serum Albumin
  • chitosan that has a molecular weight between 100 to 1000 kD is solved in acid solution.
  • the fucoidan solution that is prepared with bi-distilled or distilled water and has a pH value between 5.5 to 6.0 is added onto the chitosan solution that has turned into an acidic solution and stirred in a homogenizer or a low RPM stirrer and has a pH value between 2.0 to 5.0.
  • the mixture ratio of chitosan and fucoidan solutions is 0.5: 2.0.
  • the obtained solution has chitosan (0.25%, 0.50% and 0.75%), fucoidan (1.5%, 1.75% and 2.5%) and protein (0.25%, 0.50% and 0.75%) concentrations.
  • Chitosan-fucoidan multiparticulates are prepared via the interaction of the oppositely loaded groups stirred in the homogenizer or stirrer. Then the morphological structure and particle sizes of the microparticulates that are centrifuged, washed and lyophilized are controlled.
  • the BSA release of multiparticulates is realized at pH value 7.4, 37 ⁇ 0.1 °C in the PBS and the BSA content is established with spectrophotometric method, at 595 nm.
  • the structural integrity of the BSA is checked by the SDS- PAGE.
  • chitosan-fucoidan microparticulates which are BSA loaded and have particle sizes between 0.61-1.23 micrometers and have spherical structures.
  • Figure 1 and Figure 2 show the Scanning Electron Microscopy (SEM) photographs of the chitosan-fucoidan microparticulates which are BSA loaded).
  • SEM Scanning Electron Microscopy
  • the encapsulation efficiency of the microparticulates varies between 51.8% and 89.5%. The highest efficiency of encapsulation is obtained from multiparticulates that include 2.5% of fucoidan.
  • Chitosan, fucoidan and BSA concentrations affect the protein release from multiparticulates.
  • the origin of chitosan is important in BSA release. When the chitosan concentration is increased a decreasing effect in the release is observed. When the protein quantity is decreased an increase in BSA release is observed.
  • the specifications of the microparticulates could be modulated via the changes in the formula variables.
  • the fucoidan multiparticulate which is a scope of invention in drug carrier systems increases the convenience in industry with its no need of organic solvents and excipients such as catalysts, its very short duration and simple preparation method and low cost.
  • the release time was extended up to 6 days for fucoidan microspheres prepared at two different rpm rates, and while the effect of high amount drug release within the first hours called burst effect was decreased to 20%, this effect was decreased to 42% at most for the crosslinked chitosans, however it was seen that whole drug was released within the first 8 hours in the non-crosslinked chitosan formulations.
  • drug release for fucoidan microspheres complied with the 0 degree kinetic after the first 8 hours, for chitosan micro particles, such a release kinetic was not seen, on the contrary, for the crosslinked chitosan microspheres, a triphasic release profile was seen.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

Les systèmes multiparticulaires du fucoidane sont, en tant que système vecteur de médicament, préparés avec l'interaction du fucoidane. Un polysaccharide a un caractère anionique avec le chitosane et aussi un polysaccharide et a des caractéristiques cationiques. Dans la préparation de ces systèmes multiparticulaires, ni les solvants organiques, ni les excipients ne sont utilisés comme catalyseurs.
PCT/TR2005/000015 2005-02-25 2005-02-25 Systemes vecteurs du medicament multiparticulaire fucoidane WO2006091180A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/TR2005/000015 WO2006091180A2 (fr) 2005-02-25 2005-02-25 Systemes vecteurs du medicament multiparticulaire fucoidane

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/TR2005/000015 WO2006091180A2 (fr) 2005-02-25 2005-02-25 Systemes vecteurs du medicament multiparticulaire fucoidane

Publications (2)

Publication Number Publication Date
WO2006091180A2 true WO2006091180A2 (fr) 2006-08-31
WO2006091180A3 WO2006091180A3 (fr) 2007-03-15

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PCT/TR2005/000015 WO2006091180A2 (fr) 2005-02-25 2005-02-25 Systemes vecteurs du medicament multiparticulaire fucoidane

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015161192A1 (fr) * 2014-04-17 2015-10-22 Memorial Sloan Kettering Cancer Center Nanogels à base de fucoidan et leurs procédés d'utilisation et de fabrication
CN106176666A (zh) * 2016-07-14 2016-12-07 青岛吉海营养科技有限公司 一种防吸潮岩藻多糖产品及其制备方法
WO2018201981A1 (fr) * 2017-05-01 2018-11-08 中国医药大学 Composition immunomagnétique, son procédé de préparation et son utilisation, et kit de traitement du cancer
US10383891B2 (en) * 2014-10-06 2019-08-20 Algamed Therapeutics (A.M.T) Ltd. Compositions comprising sulfated polysaccharides and uses thereof
CN110269842A (zh) * 2019-07-03 2019-09-24 中国人民解放军陆军军医大学第二附属医院 一种抗氧化应激的天然纳米粒制剂及其制备方法
US10736964B2 (en) 2017-05-01 2020-08-11 China Medical University Immunomagnetic nanocapsule and kit for treating cancer

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0085917A2 (fr) * 1982-02-09 1983-08-17 Amf Incorporated Milieux fibreux contenant des particules de la taille du millimicron
US4488969A (en) * 1982-02-09 1984-12-18 Amf Incorporated Fibrous media containing millimicron-sized particulates
WO1999018934A1 (fr) * 1997-10-09 1999-04-22 Vanderbilt University Dispositif d'administration de microparticules ou de nanoparticules de polymeres
US6726934B1 (en) * 1997-10-09 2004-04-27 Vanderbilt University Micro-particulate and nano-particulate polymeric delivery system
US20040136961A1 (en) * 1997-10-09 2004-07-15 Ales Prokop Nanoparticulate composition for efficient gene transfer

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0085917A2 (fr) * 1982-02-09 1983-08-17 Amf Incorporated Milieux fibreux contenant des particules de la taille du millimicron
US4488969A (en) * 1982-02-09 1984-12-18 Amf Incorporated Fibrous media containing millimicron-sized particulates
WO1999018934A1 (fr) * 1997-10-09 1999-04-22 Vanderbilt University Dispositif d'administration de microparticules ou de nanoparticules de polymeres
US6726934B1 (en) * 1997-10-09 2004-04-27 Vanderbilt University Micro-particulate and nano-particulate polymeric delivery system
US20040136961A1 (en) * 1997-10-09 2004-07-15 Ales Prokop Nanoparticulate composition for efficient gene transfer

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015161192A1 (fr) * 2014-04-17 2015-10-22 Memorial Sloan Kettering Cancer Center Nanogels à base de fucoidan et leurs procédés d'utilisation et de fabrication
US9737614B2 (en) 2014-04-17 2017-08-22 Memorial Sloan Kettering Cancer Center Fucoidan nanogels and methods of their use and manufacture
US10478506B2 (en) * 2014-04-17 2019-11-19 Memorial Sloan Kettering Cancer Center Fucoidan nanogels and methods of their use and manufacture
US10383891B2 (en) * 2014-10-06 2019-08-20 Algamed Therapeutics (A.M.T) Ltd. Compositions comprising sulfated polysaccharides and uses thereof
US11116788B2 (en) 2014-10-06 2021-09-14 Algamed Therapeutics (A.M.T) Ltd Compositions comprising sulfated polysaccharides and uses thereof
CN106176666A (zh) * 2016-07-14 2016-12-07 青岛吉海营养科技有限公司 一种防吸潮岩藻多糖产品及其制备方法
WO2018201981A1 (fr) * 2017-05-01 2018-11-08 中国医药大学 Composition immunomagnétique, son procédé de préparation et son utilisation, et kit de traitement du cancer
US10736964B2 (en) 2017-05-01 2020-08-11 China Medical University Immunomagnetic nanocapsule and kit for treating cancer
CN110269842A (zh) * 2019-07-03 2019-09-24 中国人民解放军陆军军医大学第二附属医院 一种抗氧化应激的天然纳米粒制剂及其制备方法

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Publication number Publication date
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