EP2574171A1 - Repair of fragmented dna and treatment of heavy metal intoxication by intravenous injection of nano-hydroxyapatite - Google Patents

Repair of fragmented dna and treatment of heavy metal intoxication by intravenous injection of nano-hydroxyapatite

Info

Publication number
EP2574171A1
EP2574171A1 EP10720528A EP10720528A EP2574171A1 EP 2574171 A1 EP2574171 A1 EP 2574171A1 EP 10720528 A EP10720528 A EP 10720528A EP 10720528 A EP10720528 A EP 10720528A EP 2574171 A1 EP2574171 A1 EP 2574171A1
Authority
EP
European Patent Office
Prior art keywords
hydroxyapatite
nano
heavy metal
intravenous injection
repair
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
EP10720528A
Other languages
German (de)
French (fr)
Inventor
Eman Ismail Abd El-Gawad
Sameh Abd El-Hamid Ismail Awwad
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP2574171A1 publication Critical patent/EP2574171A1/en
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K33/42—Phosphorus; Compounds 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
    • A61K9/0019—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents

Definitions

  • HAp Hydroxyapatite
  • Ca 10 (PO4)6(OH) 2 is a bioactive ceramic with a crystal structure similar to native bone and teeth minerals due to its structural similarity to bone mineral, enamel and dentin.
  • HAp ceramics have gained acceptance as bone substitute, materials in dentistry and medicine due to its ability to form bone apatite-like and has the ability to develop a direct adherent and strong bonding with the bone tissue. Moreover, it provides a scaffold or template for the formation of new bone.
  • the applications of HAp as biomaterial are: repair of bony and periodontal defects, maintenance or augmentation of alveolar ridge, ear implant, spine fusion, adjuvant to uncoated implants, maxillofacial surgery.
  • HAp has shown strong inhibitory effects on the growth of various cancers with minimal side effects, and its nanoparticles have stronger anti-tumor effect than macromolecules. Also, it could bring strong cooperative effect with chemotherapy medicine which, in turn, will result in reducing the toxicity of it.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Synthesis of nano-hydroxyapatite by an organic-inorganic complexion route. Such material was injected intravenously into rats after the exposure of these rats to LD50 of toxic heavy metal. The prepared nano-hydroxyapatite success in repair the fragmented DNA within 48 hours after injection with single dose only without any side effects. Also, heart, liver and thyroid function enzymes were evaluated and the results confirmed the bio-safe usage of this made material. Therefore, the prepared nano-hydroxyapatite can be use safely as a thereby by intravenous injection with suitable doses for different diseases such as cancer, poising and osteoporosis.

Description

REPAIR OF FRAGMENTED DNA AND TREATMENT OF HEAVY METAL INTOXICATION INTRAVENOUS INJECTION OF NANO-HYDROXYAPATITE
Technical field
Biomedical application , nanotechnology Background Art
Hydroxyapatite (HAp) is the molecular formula of which Ca10(PO4)6(OH)2 is a bioactive ceramic with a crystal structure similar to native bone and teeth minerals due to its structural similarity to bone mineral, enamel and dentin. HAp ceramics have gained acceptance as bone substitute, materials in dentistry and medicine due to its ability to form bone apatite-like and has the ability to develop a direct adherent and strong bonding with the bone tissue. Moreover, it provides a scaffold or template for the formation of new bone. The applications of HAp as biomaterial are: repair of bony and periodontal defects, maintenance or augmentation of alveolar ridge, ear implant, spine fusion, adjuvant to uncoated implants, maxillofacial surgery. HAp has shown strong inhibitory effects on the growth of various cancers with minimal side effects, and its nanoparticles have stronger anti-tumor effect than macromolecules. Also, it could bring strong cooperative effect with chemotherapy medicine which, in turn, will result in reducing the toxicity of it.
There has been an increasing concern over the discharge of heavy metals into the environment and there are several methods for heavy metal removal from wastewaters. In particular, chemical stabilization is one of the methods of reducing the leachability of heavy metals in waste materials, with forming new, less soluble mineral phases that are more stable in the environment. Hydroxyapatite is an ideal material for long- term containment of contaminants It is well documented that HAp strongly sorbs uranium and many other radionuclides and heavy metals. HAp has been investigated as a potential agent to treat heavy metal- contaminated soils, sediments, wastes, and wastewater, especially in the cases of Pb, Cd, Zn, and U. HAp is an economical and natural source of phosphate, which has a high removal capacity for divalent heavy metal ions. Although several researches achieve nano-hydroxyapatite but the tested one for intravenous injection has large particles. It was difficult to inject hydroxyapatite intravenously because the particles of this material which previously prepared were lager enough to aggregate and form secondary larger particles. These formed particles cause blockage of capillaries and leading to death. For this reason, hydroxyapatite material did not use as intravenous therapy. Until the date of issue, There is no previous work studying the effect of this material on DNA or the effect of it against heavy metal or toxic substance in vivo.
Disclosure of Invention :
Nano-hydroxyapatite had been synthesized by an organic-inorganic complexion route. Such rout succeeded in synthesis nano-hydroxyapatite in very fine spherical particles in nanosize. The advantages of this technique showed to have: low processing temperature, high molecular level homogeneity, improved purity, morphology, texture, and a scope to tailor the made compound. The surface area of the formed nano HAp was about 6 times larger than the surface area of HAp prepared in another studies which was used in intravenous injection of male Wistar rats. The transmission electron microscope showed a nano-HAp of ultra small crystals distributed in matrix as shown in figure 1 with average grain size of 40 nm. The surface area of the dried powder was 405m /g with total pore diameter 0.4621 cc/g. the average pore diameter was 45.63 A.
Tested animals were intraperitonoully injected with LD50 of toxic heavy metal after three hours the synthesized nano-hydroxyapatite was injected intravenously. The analysis results of DNA in Blood and liver samples which were collected through 48hours showed in figure 2 & 3 respectively a succeeding of nano-hydroxyapatite in repairing the fragmented DNA.
Also, heart, liver and thyroid function enzymes were evaluated as markers of general health and the results confirmed the bio-safe usage of this synthesized material. The same experiment was repeated with another concentration of nano-hydroxyapatite and the results were the same for three years and all the tested animals treated still alive with a good health until the date of issue.
The prepared nano-hydroxyapatite succeeded in repairing the fragmented DNA of the rats which had been exposed to LD50 of toxic heavy metal within 48 hours after intravenous injection with single dose only and the tested animals were alive without any side effects.
Also, heart, liver and thyroid function enzymes were evaluated as markers of general health and the results confirmed the bio-safe usage of this synthesized material. The same experiment was repeated with another concentration of nano-hydroxyapatite and the results were the same for three years.
Therefore, the prepared nano-hydroxyapatite can be used safely as a thereby by intravenous injection in suitable doses for protection against contamination of heavy metal and radioactive materials and for recovery from different diseases such as cancer and osteoporosis.
Brief Description of Drawings:
Figure 1 TEM migrograph analysis of nano-HAp with its the diffraction pattern.
Figure 2 Blood DNA electrophoresis of tested animals where a)control animal
b&c) toxic heavy metals treated animals, d&e) nano-HAp after toxic heavy metal treatment
Figure 3 Blood DNA electrophoresis of tested animals where
a) Control animal group b) Toxic heavy metal treated animals c) Toxic heavy metal treated animals d &e ) Intravenous of low concentration of nano-HAp after toxic heavy metal treatment f&g) intravenous of high concentration of nano- HAp after toxic heavy metal treatment
Figure 4 comet of DNA in blood
a) Control animal group b) Toxic heavy metal treated animals c) Toxic heavy metal treated animals d &e ) Intravenous of low concentration of nano-HAp after toxic heavy metal treatment f&g) intravenous of high concentration of nano- HAp after toxic heavy metal treatment
Figure 5 liver DNA electrophoresis of tested animals where
a) Control animal group b) Toxic heavy metal treated animals c) Toxic heavy metal treated animals d &e ) Intravenous of low concentration of nano-HAp after toxic heavy metal treatment f&g) intravenous of high concentration of nano- HAp after toxic heavy metal treatment
Figure 6 comet of DNA in liver
a) Control animal group b) Toxic heavy metal treated animals c) Toxic heavy metal treated animals d &e ) Intravenous of low concentration of nano-HAp after toxic heavy metal treatment f&g) intravenous of high concentration of nano- HAp after toxic heavy metal treatment Best Mode for carrying out the invention :
The synthesized nano-hydroxyapatite succeeded in repairing the fragmented DNA of the rats which had been exposed to LD50 of toxic heavy metal within 48 hours after intravenous injection with single dose only and the tested animals were alive without any side effects.
Therefore the synthesized nano-hydroxyapatite could be injected intravenously safely in:
1 - Repair fragmented DNA in blood and liver.
2- protection against internal contamination of heavy metal and radioactive materials which cause fragmentation of DNA.
3- different concentration suitable for treatment of many diseases, such as cancer and osteoporosis.

Claims

Claims
The usage of intravenous injection of synthesized nano-hydroxyapatite for :
1- repair fragmented DNA
2- medical treatment in cases of internal contamination with toxic heavy metals.
EP10720528A 2010-04-07 2010-04-14 Repair of fragmented dna and treatment of heavy metal intoxication by intravenous injection of nano-hydroxyapatite Ceased EP2574171A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EG2010040557 2010-04-07
PCT/EG2010/000019 WO2011124234A1 (en) 2010-04-07 2010-04-14 Repair of fragmented dna and treatment of heavy metal intoxication by intravenous injection of nano-hydroxyapatite

Publications (1)

Publication Number Publication Date
EP2574171A1 true EP2574171A1 (en) 2013-04-03

Family

ID=42321208

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10720528A Ceased EP2574171A1 (en) 2010-04-07 2010-04-14 Repair of fragmented dna and treatment of heavy metal intoxication by intravenous injection of nano-hydroxyapatite

Country Status (2)

Country Link
EP (1) EP2574171A1 (en)
WO (1) WO2011124234A1 (en)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6001185A (en) * 1998-10-30 1999-12-14 Huff; Carl L. Method for treatment of heavy metal contamination
US6462029B1 (en) * 1999-02-23 2002-10-08 Econugenics Compositions and methods for treating mammals with modified alginates and modified pectins
AU2007205961B2 (en) * 2006-01-12 2013-03-14 Rutgers, The State University Biomimetic hydroxyapatite synthesis

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
ALIS YOVANA PATAQUIVA-MATEUS ET AL: "Nanoparticles of hydroxyapatite: preparation, characterization and cellular approach -An Overview", REVISTA MUTIS, 1 January 2013 (2013-01-01), pages 43 - 57, XP055251961 *
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; 10 May 2005 (2005-05-10), UOTA MASAFUMI ET AL: "Synthesis of high surface area hydroxyapatite nanoparticles by mixed surfactant-mediated approach.", Database accession no. NLM16032896 *
FERRAZ M P ET AL: "Hydroxyapatite nanoparticles: A reviw of preparation methodologies", JOURNAL OF APPLIED BIOMATERIALS, JOHN WILEY & SONS, INC., NEW YORK, NY, US, vol. 2, 1 January 2004 (2004-01-01), pages 74 - 80, XP002468051, ISSN: 1045-4861 *
JUN HU ET AL: "Effect of hydroxyapatite nanoparticles on the growth and p53/c-Myc protein expression of implanted hepatic VX2 tumor in rabbits by intravenous injection.", WORLD JOURNAL OF GASTROENTEROLOGY, vol. 13, no. 20, 1 May 2007 (2007-05-01), pages 2798 - 2802, XP055097603, ISSN: 1007-9327 *
LI Y ET AL: "Current application of hydroxyapatite nanoparticles in tumor field", ZHONGGUO ZUZHI GONGCHENG YU LINCHUANG KANGFU= JOURNAL OF CLINICAL REHABILITATIVE TISSUE ENGINEERING RESEARCH, ZHONGGUO KANGFU YIXUEHUI, CN, vol. 12, no. 32, 5 August 2008 (2008-08-05), pages 6393 - 6396, XP009176023, ISSN: 1673-8225 *
See also references of WO2011124234A1 *
YUAN Y ET AL: "Size-mediated cytotoxicity and apoptosis of hydroxyapatite nanoparticles in human hepatoma HepG2 cells", BIOMATERIALS, ELSEVIER SCIENCE PUBLISHERS BV., BARKING, GB, vol. 31, no. 4, 1 February 2010 (2010-02-01), pages 730 - 740, XP026762081, ISSN: 0142-9612, [retrieved on 20091202], DOI: 10.1016/J.BIOMATERIALS.2009.09.088 *

Also Published As

Publication number Publication date
WO2011124234A1 (en) 2011-10-13

Similar Documents

Publication Publication Date Title
Epple Review of potential health risks associated with nanoscopic calcium phosphate
Khajuria et al. Accelerated bone regeneration by nitrogen-doped carbon dots functionalized with hydroxyapatite nanoparticles
Balhuc et al. Dental applications of systems based on hydroxyapatite nanoparticles—an evidence-based update
Shokouhinejad et al. Bioactivity of EndoSequence root repair material and bioaggregate
Rahimi et al. Osseous reaction to implantation of two endodontic cements: Mineral trioxide aggregate (MTA) and calcium enriched mixture (CEM)
Kramer et al. Synthesis and characterization of cobalt-substituted hydroxyapatite powders
Fan et al. Ag-loaded mesoporous bioactive glasses against Enterococcus faecalis biofilm in root canal of human teeth
Wennerberg et al. In vivo stability of hydroxyapatite nanoparticles coated on titanium implant surfaces.
Liu et al. In vitro bioactivity and antibacterial activity of strontium-, magnesium-, and zinc-multidoped hydroxyapatite porous coatings applied via atmospheric plasma spraying
JP4953276B2 (en) Extracted tooth pulverized product applicable to highly advanced medical treatment, decalcified powder derived from extracted tooth, method for preparing composite of decalcified powder and apatite, and pulverizer
ES2929118T3 (en) Magnesium phosphate hydrogels
Sobczak-Kupiec et al. Effect of calcination parameters on behavior of bone hydroxyapatite in artificial saliva and its biosafety
Ciobanu et al. Sm: HAp nanopowders present antibacterial activity against Enterococcus faecalis
Rossi et al. Effect of strontium ranelate on bone mineral: analysis of nanoscale compositional changes
Majhooll et al. A brief review on biomedical applications of hydroxyapatite use as fillers in polymer
Acton Phosphates—Advances in Research and Application: 2013 Edition
Farag et al. The combined antibacterial and anticancer properties of nano Ce-containing Mg-phosphate ceramic
Degli Esposti et al. Antimicrobial activity of remineralizing ion-doped amorphous calcium phosphates for preventive dentistry
Nayak et al. Physiochemical and bactericidal activity evaluation: Silver‐augmented 3D‐printed scaffolds—An in vitro study
Awais et al. A review on the recent advancements on Therapeutic effects of ions in the physiological environments
Sindhya et al. Surface modification of coral skeleton derived nanohydroxyapatite using polymers and its in-vitro studies for bone substitute applications
Hammood et al. Access to optimal calcination temperature for nanoparticles synthesis from hydroxyapatite bovine femur bone waste
WO2011124234A1 (en) Repair of fragmented dna and treatment of heavy metal intoxication by intravenous injection of nano-hydroxyapatite
Nisa et al. Fabrication and characterization of HA-oyster shell based on biopolymer-propolis as an agent of dental enamel remineralization material
Aidaros et al. Effect of Incorporating Nano-Pearl and Nano-Seashell Particles into Fluoride-based Pits and Fissure Sealant on Enamel Remineralization of Permanent Extracted Molars: An In Vitro Study.

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20130206

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20140213

REG Reference to a national code

Ref country code: DE

Ref legal event code: R003

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 20160202