WO2007110084A1 - Pyrazinic acid copper (i) complex - Google Patents
Pyrazinic acid copper (i) complex Download PDFInfo
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- WO2007110084A1 WO2007110084A1 PCT/EG2006/000024 EG2006000024W WO2007110084A1 WO 2007110084 A1 WO2007110084 A1 WO 2007110084A1 EG 2006000024 W EG2006000024 W EG 2006000024W WO 2007110084 A1 WO2007110084 A1 WO 2007110084A1
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- complex
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- SDEHBKYTACOLOD-UHFFFAOYSA-M [O-]C(C1=NC=CN=C1)=O.[Cu+] Chemical compound [O-]C(C1=NC=CN=C1)=O.[Cu+] SDEHBKYTACOLOD-UHFFFAOYSA-M 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 12
- 206010016256 fatigue Diseases 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 210000003205 muscle Anatomy 0.000 claims abstract description 8
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims abstract description 6
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 239000002798 polar solvent Substances 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims abstract 3
- 210000000056 organ Anatomy 0.000 claims abstract 3
- 238000009835 boiling Methods 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 239000013078 crystal Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 5
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 3
- 208000007466 Male Infertility Diseases 0.000 claims description 3
- 208000010428 Muscle Weakness Diseases 0.000 claims description 3
- 206010028372 Muscular weakness Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 208000000112 Myalgia Diseases 0.000 claims description 2
- 208000013465 muscle pain Diseases 0.000 claims description 2
- 210000004165 myocardium Anatomy 0.000 claims description 2
- 230000037081 physical activity Effects 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 238000002371 ultraviolet--visible spectrum Methods 0.000 claims description 2
- 241000700159 Rattus Species 0.000 claims 5
- 230000006872 improvement Effects 0.000 claims 4
- 210000000130 stem cell Anatomy 0.000 claims 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- 239000010949 copper Substances 0.000 claims 3
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims 2
- 201000010046 Dilated cardiomyopathy Diseases 0.000 claims 2
- 239000003963 antioxidant agent Substances 0.000 claims 2
- 230000003078 antioxidant effect Effects 0.000 claims 2
- 206010003883 azoospermia Diseases 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims 2
- 230000010534 mechanism of action Effects 0.000 claims 2
- 208000008634 oligospermia Diseases 0.000 claims 2
- 230000036616 oligospermia Effects 0.000 claims 2
- 231100000528 oligospermia Toxicity 0.000 claims 2
- 230000000704 physical effect Effects 0.000 claims 2
- 239000002244 precipitate Substances 0.000 claims 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 108010075016 Ceruloplasmin Proteins 0.000 claims 1
- 102100023321 Ceruloplasmin Human genes 0.000 claims 1
- 102000008186 Collagen Human genes 0.000 claims 1
- 108010035532 Collagen Proteins 0.000 claims 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
- 102000020856 Copper Transport Proteins Human genes 0.000 claims 1
- 108091004554 Copper Transport Proteins Proteins 0.000 claims 1
- 102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 claims 1
- 108090000365 Cytochrome-c oxidases Proteins 0.000 claims 1
- 102000016942 Elastin Human genes 0.000 claims 1
- 108010014258 Elastin Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 claims 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 claims 1
- 201000002481 Myositis Diseases 0.000 claims 1
- 208000027089 Parkinsonian disease Diseases 0.000 claims 1
- 206010034010 Parkinsonism Diseases 0.000 claims 1
- 102000004669 Protein-Lysine 6-Oxidase Human genes 0.000 claims 1
- 108010003894 Protein-Lysine 6-Oxidase Proteins 0.000 claims 1
- 206010072020 Pyospermia Diseases 0.000 claims 1
- 102000019197 Superoxide Dismutase Human genes 0.000 claims 1
- 108010012715 Superoxide dismutase Proteins 0.000 claims 1
- 206010070863 Toxicity to various agents Diseases 0.000 claims 1
- 102000003425 Tyrosinase Human genes 0.000 claims 1
- 108060008724 Tyrosinase Proteins 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 230000023555 blood coagulation Effects 0.000 claims 1
- 239000003114 blood coagulation factor Substances 0.000 claims 1
- 150000003943 catecholamines Chemical class 0.000 claims 1
- 210000004970 cd4 cell Anatomy 0.000 claims 1
- 230000024245 cell differentiation Effects 0.000 claims 1
- 229920001436 collagen Polymers 0.000 claims 1
- 229910052802 copper Inorganic materials 0.000 claims 1
- 229960003638 dopamine Drugs 0.000 claims 1
- 229920002549 elastin Polymers 0.000 claims 1
- 229910002804 graphite Inorganic materials 0.000 claims 1
- 239000010439 graphite Substances 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 230000036737 immune function Effects 0.000 claims 1
- 210000000987 immune system Anatomy 0.000 claims 1
- 238000002329 infrared spectrum Methods 0.000 claims 1
- 230000010438 iron metabolism Effects 0.000 claims 1
- 230000003907 kidney function Effects 0.000 claims 1
- 238000002372 labelling Methods 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 230000000527 lymphocytic effect Effects 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- 238000005259 measurement Methods 0.000 claims 1
- 230000004899 motility Effects 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 239000012454 non-polar solvent Substances 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 239000008188 pellet Substances 0.000 claims 1
- 230000019612 pigmentation Effects 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 230000004044 response Effects 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 230000021595 spermatogenesis Effects 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- 231100000419 toxicity Toxicity 0.000 claims 1
- 230000001988 toxicity Effects 0.000 claims 1
- 230000007704 transition Effects 0.000 claims 1
- 238000002424 x-ray crystallography Methods 0.000 claims 1
- 208000000509 infertility Diseases 0.000 abstract description 7
- 230000036512 infertility Effects 0.000 abstract description 7
- 231100000535 infertility Toxicity 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 5
- 239000003085 diluting agent Substances 0.000 abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract 2
- 230000002929 anti-fatigue Effects 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 239000002075 main ingredient Substances 0.000 abstract 1
- 230000004720 fertilization Effects 0.000 description 5
- VRQQSSGVFHNAHO-UHFFFAOYSA-L dichlorocopper;pyrazine-2-carboxylic acid Chemical compound Cl[Cu]Cl.OC(=O)C1=CN=CC=N1 VRQQSSGVFHNAHO-UHFFFAOYSA-L 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 230000019100 sperm motility Effects 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 230000000869 mutational effect Effects 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
- 101150099632 Dd gene Proteins 0.000 description 1
- 102000001039 Dystrophin Human genes 0.000 description 1
- 108010069091 Dystrophin Proteins 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000003019 respiratory muscle Anatomy 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages
Definitions
- Copper (I) chloride complex of pyrazinic acid is prepared, characterized by elemental analysis, IR, UV- visible spectra and its crystal structure determined by single crystal diffraction methods for the first time.
- This compound is found to exhibit a very positive influence as a drug in a pharmaceutical acceptable composition for different incurable diseases, e.g. myopathy or weakness of muscles in general, infertility ,etc. To the best of our knowledge this is the first drug having such effect as given in the following parts .
- Duchene dystrophy is an x linked disorder primarily affecting skeletal muscle , caused by lack of dystrophin - the protein product of DD gene located on XP21. These patients are males who suffer from progressive muscle weakness extending to both cardiac and respiratory muscle failure. DD patients die at the age of 25-30 years old of either respiratory and / or cardiac failures. Females are healthy carriers . Several trials for both drug and genetic treatment did not give satisfactory results.
- Male infertility is a multi factorial disease process with a number of potential contributing causes . Considering the majority of male infertility cases are due to deficient sperm production of unknown origin , environmental and mutational factors must be evaluated .
- Cardiomyopathy is this fatal disease where all clinical trials are just symptomatic treatment for heart failure and the hope for these patients are cardiac transplantation.
- a process for the preparation of pyrazinic acid- copper chloride complex by dissolving the components in a polar solvent e.g. acetone, water, ethanol, ...as a red bright microcrystalline powder.
- a polar solvent e.g. acetone, water, ethanol, ...as a red bright microcrystalline powder.
- a m comprises administering to say human person an effective amount of the complex in a pharmaceutically acceptable composition with other acceptable vitamins, carriers, diluent and or excipient.
- concentration of the complex and other components depends on different factors, e.g. type and reason of weakness of the muscles, age of the patient, etc.
- a method for treatment of Fatigue comprises administering to say a human person the copper chloride-pyrazinic acid complex and /or a pharmaceutically acceptable composition of the complex .
- the concentration of the complex in the pharmaceutically acceptable form is variable and depends on several factors, e.g. age of the patient, reason of fatigue, etc.
- a method for treatment of infertility in men comprises administering to say a man the pyrazinic acid complex or apharmaceutically acceptable composition containing the complex, acceptable carrier, diluent, excipient.
- Solid dosage forms for oral administration may include capsules, tablets, pills and granules, In such solid dosage forms, the pyrazinic acid-copper chloride complex may be admixed with at least one inert diluent
- Such dosage forms may also comprise , as is normal practice, additional substances other than inert diluents, e.g. ascorbic acid, other vitamins, etc.
- additional substances other than inert diluents e.g. ascorbic acid, other vitamins, etc.
- the dosage forms may also comprise buffering agents
- An effective amount of a copper chloride -pyrazinic acid complex is administered orally to a human person.
- the composition for this purpose is presented as capsules, tablets ,etc.
- the specific dose level for a particular person depends on a variety of factors including age, general health, sex, diet, body weight, time of administration, as will be mentioned in details for each case.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a process for the preparation of a complex of pyrazinic acid and copper (I) chloride, by dissolving the components in a polar solvent, e.g. water, ethanol, acetone and boiling, allowing the mixture to cool, and stand over several hours to yield the complex [CuCl (C4H5N2CO2) ].2H2O. The present invention provides methods for treatment of Fatigue, Infertility, Weakness of muscles, in human requiring such treatment, comprising administering to say a person, an anti-fatigue, etc., effective amount of the complex having the above formula or a pharmaceutical composition comprising the complex together with a pharmaceutically acceptable carrier, diluent and/or excipient. The concentration of the complex (main ingredient) in the pharmaceutical composition depends on. several factors, e.g. type and degree of disease, age of patient, damage of organ or organs.
Description
Myofertolan A Master Key For Incurable
Diseases
Technical Field Drugs
Background
Copper (I) chloride complex of pyrazinic acid is prepared, characterized by elemental analysis, IR, UV- visible spectra and its crystal structure determined by single crystal diffraction methods for the first time. This compound is found to exhibit a very positive influence as a drug in a pharmaceutical acceptable composition for different incurable diseases, e.g. myopathy or weakness of muscles in general, infertility ,etc. To the best of our knowledge this is the first drug having such effect as given in the following parts .
Duchene dystrophy (DD) is an x linked disorder primarily affecting skeletal muscle , caused by lack of dystrophin - the protein product of DD gene located on XP21. These patients are males who suffer from progressive muscle weakness extending to both cardiac and respiratory muscle failure. DD patients die at the age of 25-30 years old of either respiratory and / or cardiac failures. Females are healthy carriers .Several trials for both drug and genetic treatment did not give satisfactory results.
Male infertility is a multi factorial disease process with a number of potential contributing causes . Considering the majority of male infertility cases are due to deficient sperm production of unknown origin , environmental and mutational factors must be evaluated .
The treatment of male factor infertility is a rapidly developing field. Introduction of microsurgical fertilization techniques allows assisted conception units to treat couples who previously would not have benefited from in vitro fertilization techniques . However these techniques are only used for the minority of sub-fertile men in andrological practice. Many subfertile men are still treated pharmacologically or by sperm selection methods to enhance sperm fertilization ability. Numerous pharmacological compound have been described that enhance sperm motility and thus potentially sperm
fertilizing capacity. Sperm motility plays an important role in the normal fertilization process. Poor sperm motility (<50% motile sperm with <2+ forward progression according to WHO protocol ) is considered a major factor in diminished rates of fertilization Medical trials for male non obstructive infertility by hormonal replacement, corticosteroids (in immunes infertility) , mutational therapies but results were not satisfactory. Chronic fatigue is world wide complaint affecting the productivity of a good percentage of the population . Chronic fatigue includes unexplained fatigue, chronic fatigue syndrome and fibromyalgia. In all types of fatigue the complex relieved the muscle pain, increased the physical activity and productivity and associated depression.
Cardiomyopathy is this fatal disease where all clinical trials are just symptomatic treatment for heart failure and the hope for these patients are cardiac transplantation.
Disclosure of the Invention
According to one broad form of the invention there is provided a process for the preparation of pyrazinic acid- copper chloride complex by dissolving the components in a polar solvent e.g. acetone, water, ethanol, ...as a red bright microcrystalline powder.
According to another broad form of the invention there is provided a m comprises administering to say human person an effective amount of the complex in a pharmaceutically acceptable composition with other acceptable vitamins, carriers, diluent and or excipient. The concentration of the complex and other components depends on different factors, e.g. type and reason of weakness of the muscles, age of the patient, etc.
According to another broad form of the invention there is provided a method for treatment of Fatigue . The method comprises administering to say a human person the copper chloride-pyrazinic acid complex and /or a pharmaceutically acceptable composition of the complex . The concentration of the complex in the pharmaceutically acceptable form is variable and depends on several factors, e.g. age of the patient, reason of fatigue, etc. According to a further broad form of the invention there is provided a method for treatment of infertility in men, The method comprises administering to say a man the pyrazinic acid complex or apharmaceutically acceptable composition containing the complex, acceptable carrier, diluent, excipient.
Solid dosage forms for oral administration may include capsules, tablets, pills and granules, In such solid dosage forms, the pyrazinic acid-copper chloride complex may be admixed with at least one inert diluent
Such dosage forms may also comprise , as is normal practice, additional substances other than inert diluents, e.g. ascorbic acid, other vitamins, etc. In the case of capsules the dosage forms may also comprise buffering agents
Best: mode and other modes for carrying out the invention
An effective amount of a copper chloride -pyrazinic acid complex, to achieve a desired level of improving fatigue, infertility, weakness of muscles, etc., is administered orally to a human person. The composition for this purpose is presented as capsules, tablets ,etc. The specific dose level for a particular person depends on a variety of factors including age, general health, sex, diet, body weight, time of administration, as will be mentioned in details for each case.
Claims
1. Preparation, physical proper-ties and crystal structure of [CuCl (pyrazinic acid) 2] .2H2O complex
Preparation of the complex
A suspension of copper (I) chloride in aqueous/acetone solution (1:1 v/v) was added drop wisely to pyrazinic acid (31 g) dissolved in boiled acetone (1 L) with continuous boiling and stirring until a clear reddish solution mixture obtained. The final mixture was cooled and allowed to stand over several hours to deposit a red microcrystalline precipitate of the complex. The precipitate was filtered off at the pump and washed several times with acetone and dried in vacuum. Yield is about 65%. Analytical data: Found: C 31.1.; H 3.0, N 14.0; Cl 9.7; Cu 16.6%. Calculated for C10H12 N4CuCl: C 31.2; H 3.2; N 14.1; Cl 9.3 Cu 16.6 %..
Physical proper-ties:
Color : bright red-brown microcrystalline powder Stability: the complex is sufficiently stable when well-dried
Solubility: the complex is insoluble in non polar solvents, e.g. benzene, carbon tetrachloride, etc., and insoluble in polar solvents: water, methanol, ethanol, acetone, but soluble in these solvents upon heating in inert atmosphere, otherwise oxidation takes place. UV-visible spectra: Solid sample mulled in nujol shows an absorption band due to Cu-L Charge Transfer transition at 425 nm.
Infrared spectrum: exhibits ν C=O band around 1700 cm-1, and ν C-O around 1350 cm-1 (KBr pellets) The composition of the complex formulated as [CuCl (pyrazinic acid) 2]. 2H2O was confirmed by the single crystal diffraction.
X-ray crystallography: empirical formula : C10H12ClCuN4O6, formula weight: 383.24,
Orthorhombic, space group P21212, unit cell dimensions: a = 30.693(6)Ǻ, b = 3.6405 (7) Å , c = 6.0918(12) Å, alpha = 90˚, beta = 90˚, gamma =
90˚ .volume = 680.7(2) Ǻ, Z = 2. Density, calc. = 1.837 itim-1. The X-ray single crystal data were collected on a modified STOE four-circle diffract meter. Crystal size 0.35 x 0.24 x 0.15 mm. Graphite mono achromatized Mo Kα radiation ( λ = 0.71069 Å) with the w scan technique was used to collect the data set. The accurate unit cell parameters were determined and refined by least-squares method. The structure was solved by direct methods and refined by full-matrix least squares methods on F2, using SHELXTL /PC V 5.03 program package . Goodness of fit on the F2 is 1.258. Maximum and minimum peaks in the final difference Fourier synthesis were 1.030 and - 1.141 eǺ-3.
The attached figure shows the asymmetric unit along with the labeling scheme
2.Toxicity of the complex
Seventy two rats (250+/-2.0 g b.wt) were randomly located into 12 groups of 6 rats each
Rats were observed for any toxic symptoms or signs of discomfort . Mortality in each group were recorded with
24 hrs.The LD50 was calculated according to Behecens and karbere (1970)
LD50 (I. P.) (oral) =1104.17 mg/kg
LD50 (intrapperitoneally ) 128 mg/Kg
3. Bioavailability studies on rats
Our study on rats Included five groups ,gr.l control, 2 receiving cu ,gr.2 pyrazinic ,gr3 complex with large dose ,&gr.5 receiving complex with small dose. There was no significant difference between control groups and other groups regarding the liver and , kidney functions . Complete blood picture were done for all groups gr. 4&5 receiving the complex showed increase of lymphocytic count ,but not exceeding the normal range suggesting its role in immune function .Lipid profile for all the groups didn't show significant difference.
4. Clinical trials for treatment of weakness of muscles
The complex used in treatment of muscle weakness for different underlying causes (muscle dystrophies post stroke weakness , ..Clinical improvement in DMS patients is dose dependant ,affected by the age ,weight & degree of dystrophy .When the patient reaches the optimum dose
onset of improvement in muscle power is observed within hours of drug intake .
5. Clinical trials in Cardiomyopathy
The complex improved all cases of dilated Cardiomyopathy secondary to Duchenne muscle dystrophy And 80% of cases of dilated cardiomyopathy due to other causes . Improvement is shown both clinically and in the ECHO cardiographic measurements .
6. Male Infertility
Our study included 20 patients ,9 patients azospermic, 6 acino- terato- pyospermia , 5 acino- oligo spermia , seven out of nine patients of azospermic count increased to (1.5-3 millions /hpf ) within 6 weeks of treatment and two of them got healthy babies while the other- Two cases showed no response to treatment ,while oligospermia showed doubling of the count within 1 month of treatment .four cases got also healthy babies . All cases showed significant improvement of motility.
7 Clinical trials for treatment of Fatigue in humans
In all types of fatigue the complex relieved the muscle pain , increased the physical activity and productivity and associated depression The drug improves markedly the agonizing fatigue in cases of parkinsonism ,myositis, disseminated sclerosis..
8.Mechanism of action
The drug showed multiple system effect which suggests a common mechanism of action to link between effect on spermatogenesis effect on muscle weakness, on Immune system and improving cardiac muscle in cardio myopathy patients . We hypothysed that the drug may have a role on stimulating the stem cells present in the various organs to differentiate .ODR hypotheses was proved by studying the effect of the drug both invivo and invitro on the stem cell differentiation. Invivo we measured the stem cell count together with CD8 and CD4 cells before, and at regular intervals of medication .There is a significant decrease in stem cell count with an increase in CD4 and CD8 number with no disturbance of CD4/CD8
Its well known that copper is essential for the proper functioning of copper-dependant enzymes, including cytochrome C oxidase (energy production ) , superoxide dismutase (antioxidant protection) , tyrosinase (pigmentation) , dopamine hydroxylase (catecholamine production) , lysyl oxidase (collagen and elastin formation ) , clotting factor v (blood clotting), and ceruloplasmin (antioxidant protection, iron metabolism ,and copper transport) .
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/000,704 US20110183951A1 (en) | 2006-03-27 | 2006-06-25 | Copper (1) Complex |
| US12/238,001 US20090105207A1 (en) | 2006-06-25 | 2008-09-25 | Copper (1) Complex |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EG2006030113 | 2006-03-27 | ||
| EG2006030113 | 2006-03-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2007110084A1 true WO2007110084A1 (en) | 2007-10-04 |
Family
ID=38540816
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EG2006/000024 WO2007110084A1 (en) | 2006-03-27 | 2006-06-25 | Pyrazinic acid copper (i) complex |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2007110084A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9756079B2 (en) | 2007-05-30 | 2017-09-05 | Cupp Computing As | System and method for providing network and computer firewall protection with dynamic address isolation to a device |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002070496A1 (en) * | 2001-03-01 | 2002-09-12 | Consiglio Nazionale Delle Ricerche | Nitric oxide donors based on metallic centres |
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2006
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002070496A1 (en) * | 2001-03-01 | 2002-09-12 | Consiglio Nazionale Delle Ricerche | Nitric oxide donors based on metallic centres |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9756079B2 (en) | 2007-05-30 | 2017-09-05 | Cupp Computing As | System and method for providing network and computer firewall protection with dynamic address isolation to a device |
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