CN100493514C - Composite medicine of creatine phosphate sodium and magnesium salt - Google Patents
Composite medicine of creatine phosphate sodium and magnesium salt Download PDFInfo
- Publication number
- CN100493514C CN100493514C CNB2005100883937A CN200510088393A CN100493514C CN 100493514 C CN100493514 C CN 100493514C CN B2005100883937 A CNB2005100883937 A CN B2005100883937A CN 200510088393 A CN200510088393 A CN 200510088393A CN 100493514 C CN100493514 C CN 100493514C
- Authority
- CN
- China
- Prior art keywords
- magnesium
- phosphate sodium
- creatine phosphate
- medicine
- composition
- 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.)
- Expired - Fee Related
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- 239000003814 drug Substances 0.000 title claims abstract description 59
- 159000000003 magnesium salts Chemical class 0.000 title claims abstract description 37
- RNTXMYSPASRLFT-UHFFFAOYSA-L disodium;2-[[n'-[hydroxy(oxido)phosphoryl]carbamimidoyl]-methylamino]acetate Chemical compound [Na+].[Na+].OC(=O)CN(C)C(N)=NP([O-])([O-])=O RNTXMYSPASRLFT-UHFFFAOYSA-L 0.000 title claims abstract description 19
- 239000002131 composite material Substances 0.000 title description 4
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 claims description 251
- 239000011734 sodium Substances 0.000 claims description 127
- 229910052708 sodium Inorganic materials 0.000 claims description 124
- 239000011777 magnesium Substances 0.000 claims description 85
- 229910052749 magnesium Inorganic materials 0.000 claims description 70
- 229940091250 magnesium supplement Drugs 0.000 claims description 70
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 59
- 238000002347 injection Methods 0.000 claims description 52
- 239000007924 injection Substances 0.000 claims description 52
- 239000000843 powder Substances 0.000 claims description 47
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 44
- 239000000203 mixture Substances 0.000 claims description 38
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 32
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 22
- 239000001755 magnesium gluconate Substances 0.000 claims description 19
- 229960003035 magnesium gluconate Drugs 0.000 claims description 19
- 235000015778 magnesium gluconate Nutrition 0.000 claims description 19
- IAKLPCRFBAZVRW-XRDLMGPZSA-L magnesium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;hydrate Chemical compound O.[Mg+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O IAKLPCRFBAZVRW-XRDLMGPZSA-L 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 17
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 17
- NFFJLMKHRCXLJO-UHFFFAOYSA-L magnesium;2-aminobutanedioate Chemical compound [Mg+2].[O-]C(=O)C(N)CC([O-])=O NFFJLMKHRCXLJO-UHFFFAOYSA-L 0.000 claims description 13
- -1 magnesium salt compound Chemical class 0.000 claims description 12
- 239000002552 dosage form Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 238000012856 packing Methods 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000005715 Fructose Substances 0.000 claims description 5
- 229930091371 Fructose Natural products 0.000 claims description 5
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 4
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 claims description 4
- 239000004137 magnesium phosphate Substances 0.000 claims description 4
- 229960002261 magnesium phosphate Drugs 0.000 claims description 4
- 229910000157 magnesium phosphate Inorganic materials 0.000 claims description 4
- 235000010994 magnesium phosphates Nutrition 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- MQHWFIOJQSCFNM-UHFFFAOYSA-L Magnesium salicylate Chemical compound [Mg+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O MQHWFIOJQSCFNM-UHFFFAOYSA-L 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 2
- 239000001177 diphosphate Substances 0.000 claims description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 2
- 235000011180 diphosphates Nutrition 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 2
- 239000011654 magnesium acetate Substances 0.000 claims description 2
- 229940069446 magnesium acetate Drugs 0.000 claims description 2
- 235000011285 magnesium acetate Nutrition 0.000 claims description 2
- 239000001095 magnesium carbonate Substances 0.000 claims description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
- 229960001708 magnesium carbonate Drugs 0.000 claims description 2
- 235000014380 magnesium carbonate Nutrition 0.000 claims description 2
- 229960005336 magnesium citrate Drugs 0.000 claims description 2
- 239000004337 magnesium citrate Substances 0.000 claims description 2
- 235000002538 magnesium citrate Nutrition 0.000 claims description 2
- UHNWOJJPXCYKCG-UHFFFAOYSA-L magnesium oxalate Chemical compound [Mg+2].[O-]C(=O)C([O-])=O UHNWOJJPXCYKCG-UHFFFAOYSA-L 0.000 claims description 2
- 229940072082 magnesium salicylate Drugs 0.000 claims description 2
- 229940095060 magnesium tartrate Drugs 0.000 claims description 2
- 229940023568 magnesium valproate Drugs 0.000 claims description 2
- MUZDLCBWNVUYIR-ZVGUSBNCSA-L magnesium;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Mg+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O MUZDLCBWNVUYIR-ZVGUSBNCSA-L 0.000 claims description 2
- LKLLHOIUJVEAGU-UHFFFAOYSA-L magnesium;2-propylpentanoate Chemical compound [Mg+2].CCCC(C([O-])=O)CCC.CCCC(C([O-])=O)CCC LKLLHOIUJVEAGU-UHFFFAOYSA-L 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 claims description 2
- 208000031225 myocardial ischemia Diseases 0.000 abstract description 11
- 229940090044 injection Drugs 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
- 230000037396 body weight Effects 0.000 description 14
- 239000008215 water for injection Substances 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 9
- 229930195725 Mannitol Natural products 0.000 description 9
- 239000000594 mannitol Substances 0.000 description 9
- 235000010355 mannitol Nutrition 0.000 description 9
- ISYHFARMUCCYDZ-DKWTVANSSA-N (2s)-2-aminobutanedioic acid;magnesium Chemical compound [Mg].OC(=O)[C@@H](N)CC(O)=O ISYHFARMUCCYDZ-DKWTVANSSA-N 0.000 description 8
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 8
- 229910001425 magnesium ion Inorganic materials 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 8
- 229920000053 polysorbate 80 Polymers 0.000 description 8
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
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- 230000000694 effects Effects 0.000 description 6
- 230000002107 myocardial effect Effects 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 102000019197 Superoxide Dismutase Human genes 0.000 description 5
- 108010012715 Superoxide dismutase Proteins 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 150000001768 cations Chemical class 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 229940093181 glucose injection Drugs 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 230000003387 muscular Effects 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000003708 ampul Substances 0.000 description 4
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
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- 235000010265 sodium sulphite Nutrition 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- 230000009471 action Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
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- 210000002064 heart cell Anatomy 0.000 description 1
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- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000007654 ischemic lesion Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 229940047465 magnesium gluconate oral solution Drugs 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000008065 myocardial cell damage Effects 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- BYTCDABWEGFPLT-UHFFFAOYSA-L potassium;sodium;dihydroxide Chemical compound [OH-].[OH-].[Na+].[K+] BYTCDABWEGFPLT-UHFFFAOYSA-L 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 229940079877 pyrogallol Drugs 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a combination medicine of Creatine phosphate sodium and magnesium salt, wherein the weight ratio of Creatine phosphate sodium and magnesium salt is between the range of 1:0.001-5, preferably 1:0.01-0.2, more preferably 1:0.02-0.1. The combination medicine has good synergy in treating myocardial ischemia.
Description
Technical field the invention belongs to medical technical field, relates to the composition of medicine of a kind of Creatine Phosphate Sodium and magnesium salt.
Background technology phosphagen (creatine phosphate, CP) be the intravital a kind of bioactive substance of people, mainly be present in organ or tissues such as cardiac muscle, skeletal muscle, brain, it is the energy source of supply that body weight for humans is wanted, be to participate in one of metabolic important substance of cellular energy, be the ATP makeup energy, and ATP is a topmost energy source in any cellular process.
In recent years; discover that phosphagen has important pharmacological action; it is a kind of important myocardial protective agent; its sodium salt chemical compound Creatine Phosphate Sodium has been widely used in clinical; Creatine Phosphate Sodium is applied to treat in myocardial ischemia, the cardiac operation the unusual diseases of energy metabolism of myocardial such as protection cardiac muscle, and the molecular structural formula of Creatine Phosphate Sodium is as follows
Magnesium ion (Mg
2+) be important ion necessary in the body, be many enzymes keep active, indispensable a kind of coenzyme, Mg in the body
2+The histiocyte function being had regulate and the participation effect, is the human body Na that continues
+, K
+, Ca
2+The 4th cation afterwards, its content is only second to K in cell
+The magnesium of human body 33% is present in the cell, and all the other major parts are deposited on skeleton with magnesium phosphate or magnesium carbonate form, and about 1% is positioned at extracellular fluid.Magnesium can catalysis or is activated 300 plurality of enzymes systems; Be that ATP produces and the necessary cation that plays a role in the body; Participate in the generation of vivo oxidation phosphorylation process, DNA and RNA, the structure of proteinic synthetic and all films; Mg
2+And Mg
2+-ATP chelate has regulating action to glycolysis; Mg
2+Also can keep K in the cell
+Stable, magnesium is Na
+-K
+The essential factor of the activator of-ATP enzyme and cellular oxidation phosphorylation can be kept the inside and outside ionic permeability of cell, and magnesium is as natural physiological Ca simultaneously
2+Antagonist can suppress Ca
2+Interior stream.Clinical pathological study shows, Mg
2+The damage that myocardial ischemia-reperfusion is produced has good protective action, and is significant to reducing myocardial infarction area.Magnesium deficiency is the risk factor that multiple cardiovascular disease takes place, Clinical pathological study shows, during myocardial ischemia, the disappearance of cardiac muscle content of magnesium is that it one of changes the earliest, and the reduction of magnesium density also is one of myocardial cell injury sign the earliest in the myocardial cell, during the myocardial cell magnesium deficiency, potassium ion reduces in the cell, calcium ion increases, and causes cellular energy metabolism and ion running obstacle, the electrophysiological characteristics of influence cardiac muscle.
In view of the pathogeny complexity of relevant cardiovascular disease, Creatine Phosphate Sodium and Mg
2+Relevant cardiovascular disease there are the different mechanism of action and therapeutic effect, and simple Creatine Phosphate Sodium or the Mg of giving
2+Treatment to relevant cardiovascular disease has weak point, and is very limited for the therapeutical effect of myocardial ischemia and myocardial preservation.
Summary of the invention the purpose of this invention is to provide the composition of medicine of a kind of Creatine Phosphate Sodium and magnesium salt in order to overcome the deficiencies in the prior art part, and it not only has the pharmacological action of phosphagen, and Mg is provided
2+, make both have good pharmacology synergism.
The invention provides the composition of medicine of Creatine Phosphate Sodium and magnesium salt compound, magnesium salt is meant can provide Mg
2+Salt compounds, wherein the quality ratio range of Creatine Phosphate Sodium and magnesium elements is 1:0.001～5, promptly per 1 gram Creatine Phosphate Sodium makes up with the magnesium elements proportioning of 0.001～5 gram.
The quality ratio range of Creatine Phosphate Sodium and magnesium elements is preferably 1:0.01～0.2;
The quality ratio range of Creatine Phosphate Sodium and magnesium elements is 1:0.02～0.1 more preferably.
Magnesium ion (Mg
2+) as a kind of metal cation, can not independent exist, must be to provide by the donor substance of magnesium salt compound as magnesium elements (magnesium ion), theoretically, everyly can provide Mg
2+Salt compounds all be allowed to, magnesium salt compound of the present invention is selected from following compounds: magnesium chloride, Magnesium Aminosuccinate, magnesium sulfate, magnesium gluconate.
Further, the composition of medicine of Creatine Phosphate Sodium of the present invention and magnesium salt, magnesium salt also comprises the magnesium salt of Magnesium L-Asacorbic Acid 2-O-Phosphate, magnesium citrate, magnesium tartrate, magnesium carbonate, magnesium phosphate, magnesium acetate, magnesium oxalate, magnesium valproate, magnesium salicylate, magnesium stearate, Stepanol MG, amino acid whose magnesium salt, maleic acid, the magnesium salt of lactic acid, the magnesium salt of benzenesulfonic acid, the magnesium salt of fructose diphosphate, or the like.
The synergism of Creatine Phosphate Sodium and magnesium elements medicine can be observed in the certain quality ratio range, convenient for the purpose of, the dosage of the optimum curative effect that can show when using separately with it is used in combination.
Should be appreciated that the present invention selects the donor substance of magnesium salt compound such as magnesium chloride, Magnesium Aminosuccinate, magnesium sulfate, magnesium gluconate as magnesium elements (magnesium ion) for use, the percentage ratio of the magnesium elements that they are contained has nothing in common with each other, for example, and 1 gram magnesium chloride (molecular formula MgCl
2) to contain magnesium elements be 0.255 gram, 1 gram Magnesium Aminosuccinate [molecular formula (C
4H
6NO
4)
2Mg] to contain magnesium elements be 0.084 gram, 1 gram magnesium sulfate (molecular formula MgSO
4) to contain magnesium elements be 0.202 gram, 1 gram magnesium gluconate (molecular formula C
12H
22O
14Mg) containing magnesium elements is 0.0586 gram.
It must be understood that composition of medicine of the present invention comprises two kinds of compound modes:
The one, Creatine Phosphate Sodium and magnesium salt are made compound preparation, use the corresponding medicinal adjuvant to can be made into different compound medicine dosage forms with preparation technology.Be to be understood that, compound preparation is meant makes independent preparation with Creatine Phosphate Sodium and magnesium salt compound as medicament active composition, as injection Creatine Phosphate Sodium magnesium chloride lyophilized injectable powder, injection Creatine Phosphate Sodium Magnesium Aminosuccinate lyophilized injectable powder, the Creatine Phosphate Sodium magnesium sulfate inj, Creatine Phosphate Sodium magnesium chloride glucose injection, Creatine Phosphate Sodium magnesium chloride sodium chloride injection, Creatine Phosphate Sodium magnesium chloride fructose injection, Creatine Phosphate Sodium Magnesium Aminosuccinate invert srgar inj, Creatine Phosphate Sodium Magnesium Aminosuccinate tablet, Creatine Phosphate Sodium magnesium gluconate oral solution etc.;
The 2nd, Creatine Phosphate Sodium and magnesium salt are made independent preparation respectively, in use, patient's medication successively successively, also the preparation of the Creatine Phosphate Sodium that separates and the preparation of magnesium salt can be mixed back medication simultaneously, finally to reach the purpose of using composition of medicine of the present invention, necessary, the feature of patient's medication for convenience and expression drug regimen should be with two kinds of independent preparation packings in same medicine box;
Further, when Creatine Phosphate Sodium and magnesium salt are independent preparations, both pharmaceutical dosage forms can be identical, also can be different, as sodium phosphocreatine powder and injection and Aspartic Acid magnesium injection liquid composite reagent thing, sodium phosphocreatine powder and injection and magnesium chloride injection, sodium phosphocreatine powder and injection and magnesium sulfate inj composite reagent thing, or the like.
The composition of medicine of Creatine Phosphate Sodium of the present invention and magnesium salt, it can be any pharmaceutical dosage form of acceptable on the pharmaceutics, injectable powder for example, aqueous injection, tablet, capsule, granule, oral liquid and oral rapid release or dosage forms such as slow release or controlled release, can also be with glucose, sodium chloride, fructose, Nulomoline, xylitol, maltose etc. use the aqueous solution of (comprising intravenous injection and intravenous drip) as the intravenous injection of osmotic pressure regulator, Creatine Phosphate Sodium magnesium chloride glucose injection for example, Creatine Phosphate Sodium magnesium chloride sodium chloride injection, Creatine Phosphate Sodium magnesium chloride fructose injection, Creatine Phosphate Sodium Magnesium Aminosuccinate invert srgar inj, or the like, this class injection is referred to as " hanging transfusion " or " beating transfusion bottle " usually, normally uses by intravenous injection (comprising intravenous injection and intravenous drip).Certainly, this class I liquid I dosage form can also be used for operation on heart and be used for the cardioplegic solution use, with the cardiac muscular tissue under the protection ischemic state.
Though the active constituent of composition of medicine of the present invention can be used as unprocessed chemicals administration, but in fact, sign the necessity on medicine is being produced and used, composite reagent thing of the present invention can also comprise acceptable pharmaceutic adjuvant on the pharmaceutics, use corresponding, different pharmaceutic adjuvant and preparation technology, composition of medicine of the present invention can be made different pharmaceutical dosage forms.What those skilled in the art were appreciated that is, these pharmaceutic adjuvants be for the ease of production and processing become various dosage forms, guarantee medicine safe, effectively with factor such as stablize, and select for use according to self physicochemical property of different pharmaceutical dosage forms and medicine, can select mannitol, aminoacid, sorbitol, lactose, starch, microcrystalline Cellulose, water, Polyethylene Glycol for use as excipient, or the like; The pH value regulator can be selected hydrochloric acid, citric acid, sodium dihydrogen phosphate, sodium hydrogen phosphate, potassium hydroxide (sodium) for use, or the like; Antioxidant can be selected sodium sulfite, sodium sulfite, vitamin C for use, or the like; Metal chelating agent is selected ethylenediaminetetraacetic acid and salt thereof etc. for use.It is that those of skill in the art of the present invention know with conspicuous that the selection of pharmaceutic adjuvant is used.
The composition of medicine of Creatine Phosphate Sodium provided by the invention and magnesium salt, has good pharmacology synergism, not only provide the energy to cardiac muscular tissue, also regulate or participate in its biochemical functions by magnesium ion, utilize their synergism, reach the purpose of the rational infringement of control cardiac muscular tissue or heart cell dysfunction and cytopathy thereof, help cardiac muscular tissue and recover its function.Magnesium is the Na that continues in the human body
+, K
+, Ca
2+The 4th cation afterwards, its content is only second to K in cell
+, human body 33% magnesium is present in the cell, and all the other major parts are deposited on skeleton with magnesium phosphate or magnesium carbonate form, and only about 1% is positioned at extracellular fluid.Magnesium can catalysis or is activated 300 plurality of enzymes systems; Be that ATP produces and the necessary cation that plays a role in the body; Participate in the generation of vivo oxidation phosphorylation process, DNA and RNA, the structure of proteinic synthetic and all films; Magnesium and Mg
2+-ATP chelate has regulating action to glycolysis; Magnesium is natural physiological Ca
2+Antagonist also can be kept K in the cell
+Stable.
Further, prove the safety of the composition of medicine of Creatine Phosphate Sodium of the present invention and magnesium salt, and the magnesium salt of phosphagen of the present invention is at the effect and the superiority of treatment myocardial ischemia disease by zoopery.
One, with the safety of the magnesium salt of animal experimental observation phosphagen of the present invention.
18 of SD rats, body weight is 260 ± 10g, male and female half and half, be divided into four groups of groups at random, every group 6, each group is got magnesium chloride, Magnesium Aminosuccinate, magnesium sulfate, magnesium gluconate respectively as the magnesium elements donor substance, by the mixed solution (using dissolved in distilled water) of Creatine Phosphate Sodium 1g/kg body weight and magnesium elements 0.15g/kg body weight it is carried out lumbar injection, injection is 5 days continuously, and observation is respectively organized rat and had or not death, the mental status, diet, body weight.
The result: each is organized rat and all survives, and the mental status, diet, body weight are all normal fully.Show that Creatine Phosphate Sodium all is foolproof with magnesium chloride, Magnesium Aminosuccinate, magnesium sulfate, magnesium gluconate as the composition of medicine of magnesium elements donor substance respectively.
Two, verify that with zoopery the composition of medicine of Creatine Phosphate Sodium of the present invention and magnesium salt is in the curative effect advantage aspect the treatment myocardial ischemia.
The left bundle branch of utilization ligation rat arteria coronaria causes myocardial infarction and ischemia model (list of references: Li Bao etc., Mountain Western Medicine S University's journal, in February, 2005,36 (1): 11～12), model success rat is divided into four groups (6 every group) at random, make the magnesium elements donor substance with magnesium chloride, treat with Creatine Phosphate Sodium and low dosage magnesium elements, Creatine Phosphate Sodium and high dose magnesium elements respectively, and the Creatine Phosphate Sodium of selecting for use is made the Comparison of therapeutic group,, specific as follows with the rat model that only gives injecting normal saline as the blank group:
(1). Creatine Phosphate Sodium and low dosage magnesium elements group: inject Creatine Phosphate Sodium 50mg/kg body weight and magnesium ion 2mg/kg body weight by rat body weight;
(2). Creatine Phosphate Sodium and high dose magnesium elements group: inject Creatine Phosphate Sodium 50mg/kg body weight and magnesium ion 5mg/kg body weight by rat body weight;
(3). Creatine Phosphate Sodium group: inject Creatine Phosphate Sodium 50mg/kg body weight by rat body weight;
(4). blank group: give the rat injecting normal saline.
After medicine dissolved respectively with each group with distilled water, behind animal model success 15min, dosage injection by above each group gave relative medicine respectively by femoral vein.
Data determination: (1). the mensuration of superoxide dismutase (SOD) and lipid peroxidation product malonaldehyde (MDA): the medicine injection is after 4.5 hours, the sacrificed by exsanguination rat, get ventricular muscles, make ice normal saline tissue homogenate, measure the content of SOD enzymatic activity and MDA; Wherein the SOD assay method is pressed pyrogallol autoxidation method mensuration, and the content assaying method of MDA is pressed the thiobarbituricacid colorimetric method for determining.
(2). the mensuration of myocardial infarct size: the medicine injection is after 4.5 hours, and the sacrificed by exsanguination rat is taken out its heart immediately, and cardiac muscle is carried out TTC dyeing, separates infarcted region in the myocardium sheet, calculates the infarcted myocardium wet weight and accounts for the percentage ratio of chamber weight in wet base whole-heartedly.
Record experimental data following (n=6, x ± s): table 1
| Group/content | SOD/U.mg -1Protein | MDA/nmol.mg -1Protein | Myocardial infarct size % |
| Creatine Phosphate Sodium and low dosage magnesium elements group | 79.22±7.12?* ## | 8.01±3.39?* ** | 7.70±3.11?* ** |
| Creatine Phosphate Sodium and high dose magnesium elements group | 87.82±7.55?* ## | 8.81±3.56?* ** | 7.56±2.85?* ** |
| The Creatine Phosphate Sodium group | 62.27±6.38?# | 18.35±3.22 * | 20.61±3.23 # |
| The blank group | 47.08±6.61 | 29.95±3.27 | 32.57±4.27 |
*: with respect to blank group p＜0.01; *: with respect to Creatine Phosphate Sodium group p＜0.01; ##: with respect to Creatine Phosphate Sodium group p＜0.05; #: with respect to blank group p＜0.05
By last table data as can be seen, the left bundle branch of utilization ligation rat arteria coronaria causes the composition of medicine that gives Creatine Phosphate Sodium and magnesium salt after the myocardial infarction and ischemia model respectively, no matter low dosage magnesium salt group and high dose magnesium salt group, for the SOD content that improves cardiac muscle very significant difference (p＜0.01) is arranged, and compare with the Creatine Phosphate Sodium group that there were significant differences (p＜0.05); The cardiac damage product MDA content that causes owing to myocardial ischemia significantly reduces, and with respect to the Creatine Phosphate Sodium group very significant difference (p＜0.01) is arranged, and illustrates that the ischemic lesions to cardiac muscular tissue has very significant protective effect; The relative blank group of myocardial infarct size has the effect (p＜0.01) of highly significant, and the relative Creatine Phosphate Sodium group of myocardial infarct size group also has the effect (p＜0.01) of highly significant.
The composition of medicine of Creatine Phosphate Sodium provided by the invention and magnesium salt; compare with existing magnesium salt compound and Creatine Phosphate Sodium; provide energy by Creatine Phosphate Sodium for body; magnesium salt compound provides magnesium ion again; both different pharmacological actions have good pharmacology concertedness and complementarity; more help the treatment of myocardial ischemia and myocardial preservation, disable with fatality rate, improve prognosis and have great importance for the first aid of myocardial damage disease and rehabilitation, reduction.
The specific embodiment further prepares the composition of medicine that Creatine Phosphate Sodium of the present invention and magnesium salt are described by it with following several embodiment, but does not represent the embodiment limitation of the present invention.
Embodiment 1. injection Creatine Phosphate Sodium magnesium chloride lyophilized injectable powders
Prescription: Creatine Phosphate Sodium 50g
Magnesium chloride 5g (containing magnesium elements 1.275g)
Mannitol 17g
Tween 80 0.8g
PH regulator solution is an amount of
Water for injection adds to 500ml
The tween 80 of getting above recipe quantity dissolves with 400ml water for injection, the Creatine Phosphate Sodium that adds recipe quantity again, magnesium chloride and mannitol, fully pH=6.5～7.5 are regulated with the pH value regulator in the dissolving back, add needle-use activated carbon again and be incubated half an hour, behind the filtering needle-use activated carbon, add the injection water to 500ml, fine straining, after detection level is qualified, in 100 cillin bottles of packing into filtrate branch, carry out lyophilization by lyophilized injectable powder preparation technology, can be prepared into the lyophilized powder compound injection of 100 bottles of injections, contain the 0.5g Creatine Phosphate Sodium in every bottle of medicine, contain 0.05g magnesium chloride (being equivalent to magnesium elements 0.0128g).The quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.0255.
Embodiment 2. injection Creatine Phosphate Sodium Magnesium Aminosuccinate lyophilized injectable powders
Prescription: Creatine Phosphate Sodium 100g
Magnesium Aminosuccinate 50g (containing magnesium elements 4.2g)
Mannitol 25g
Tween 80 1.2g
Sodium sulfite 0.2g
PH regulator solution is an amount of
Water for injection adds to 800ml
The tween 80 of getting above recipe quantity dissolves with 700ml water for injection, the Creatine Phosphate Sodium that adds recipe quantity again, Magnesium Aminosuccinate, mannitol and sodium sulfite, fully pH=6.5～7.5 are regulated with the pH value regulator in the dissolving back, add needle-use activated carbon again and be incubated half an hour, behind the filtering needle-use activated carbon, add the injection water to 800ml, fine straining, after detection level is qualified, in 100 cillin bottles of packing into filtrate branch, carry out lyophilization by lyophilized injectable powder preparation technology, can be prepared into the lyophilized powder compound injection of 100 bottles of injections, contain the 1g Creatine Phosphate Sodium in every bottle of medicine, contain 0.5g Magnesium Aminosuccinate (being equivalent to magnesium elements 0.042g).The quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.042.
Embodiment 3. injection Creatine Phosphate Sodium magnesium sulfate lyophilized injectable powders
Prescription: Creatine Phosphate Sodium 50g
Magnesium sulfate 50g (containing magnesium elements 10.1g)
Mannitol 20g
Tween 80 1g
PH regulator solution is an amount of
Water for injection adds to 500ml
The tween 80 of getting above recipe quantity dissolves with 400ml water for injection, the Creatine Phosphate Sodium that adds recipe quantity again, magnesium sulfate, mannitol, fully pH=6.5～7.5 are regulated with the pH value regulator in the dissolving back, add needle-use activated carbon again and be incubated half an hour, behind the filtering needle-use activated carbon, add the injection water to 500ml, fine straining, after detection level is qualified, in 100 cillin bottles of packing into filtrate branch, carry out lyophilization by lyophilized injectable powder preparation technology, can be prepared into the lyophilized powder compound injection of 100 bottles of injections, contain the 0.5g Creatine Phosphate Sodium in every bottle of medicine, contain 0.5g magnesium sulfate (being equivalent to magnesium elements 0.101g).The quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.202.
Embodiment 4. injection Creatine Phosphate Sodium magnesium gluconate lyophilized injectable powders
Prescription: Creatine Phosphate Sodium 50g
Magnesium gluconate 50g (containing magnesium elements 2.93g)
Mannitol 20g
Tween 80 1g
PH regulator solution is an amount of
Water for injection adds to 500ml
The tween 80 of getting above recipe quantity dissolves with 400ml water for injection, the Creatine Phosphate Sodium that adds recipe quantity again, magnesium gluconate and mannitol, fully pH=6.5～7.5 are regulated with the pH value regulator in the dissolving back, add needle-use activated carbon again and be incubated half an hour, behind the filtering needle-use activated carbon, add the injection water to 500ml, fine straining, after detection level is qualified, in 100 cillin bottles of packing into filtrate branch, carry out lyophilization by lyophilized injectable powder preparation technology, can be prepared into the lyophilized powder compound injection of 100 bottles of injections, contain the 0.5g Creatine Phosphate Sodium in every bottle of medicine, contain 0.5g magnesium gluconate (being equivalent to magnesium elements 0.0293g).The quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.0586.
The composition of medicine of embodiment 5. creatine phosphate sodium freeze-dried powder pins and magnesium chloride injection
Creatine Phosphate Sodium is made the freeze-dried powder that every cillin bottle contains the 0.5g Creatine Phosphate Sodium, magnesium chloride is made the injection that every ampoule bottle contains the 0.1g magnesium chloride, after labelling, this freeze-dried powder and infusion pump are contained in the same packing box, promptly get the composition of medicine of creatine phosphate sodium freeze-dried powder pin and magnesium chloride injection, the quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.1275.
Become mixed solution after can creatine phosphate sodium freeze-dried powder pin being dissolved with the magnesium chloride injection during use and use together, also can use be mixed with the magnesium chloride injection in creatine phosphate sodium freeze-dried powder pin dissolving back, or successively use successively with an amount of water for injection.
The composition of medicine of embodiment 6. creatine phosphate sodium freeze-dried powder pins and Aspartic Acid magnesium injection liquid
Similarly, Creatine Phosphate Sodium is made the freeze-dried powder that every cillin bottle contains the 1g Creatine Phosphate Sodium, Magnesium Aminosuccinate is made the injection that every ampoule bottle contains the 1g Magnesium Aminosuccinate, after labelling, this freeze-dried powder and infusion pump are contained in the same packing box, promptly get the composition of medicine of creatine phosphate sodium freeze-dried powder pin and Aspartic Acid magnesium injection liquid, the quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.084.
Becoming mixed solution after can creatine phosphate sodium freeze-dried powder pin being dissolved with the Aspartic Acid magnesium injection liquid during use uses together, also can use be mixed with the Aspartic Acid magnesium injection liquid in creatine phosphate sodium freeze-dried powder pin dissolving back, or successively use successively with an amount of water for injection.
The composition of medicine of embodiment 7. creatine phosphate sodium freeze-dried powder pins and magnesium sulfate inj
Similarly, Creatine Phosphate Sodium is made the freeze-dried powder that every cillin bottle contains the 1g Creatine Phosphate Sodium, magnesium sulfate is made the injection that every ampoule bottle contains 0.5g magnesium sulfate, after labelling, this freeze-dried powder and infusion pump are contained in the same packing box, promptly get the composition of medicine of creatine phosphate sodium freeze-dried powder pin and magnesium sulfate inj, the quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.101.
Becoming mixed solution after can creatine phosphate sodium freeze-dried powder pin being dissolved with the Aspartic Acid magnesium injection liquid during use uses together, also can use be mixed in creatine phosphate sodium freeze-dried powder pin dissolving back with magnesium sulfate inj, or successively use successively with an amount of water for injection.
The composition of medicine of embodiment 8. creatine phosphate sodium freeze-dried powder pins and magnesium gluconate freeze-dried powder
Similarly, Creatine Phosphate Sodium is made the freeze-dried powder that every cillin bottle contains the 0.75g Creatine Phosphate Sodium, magnesium gluconate is made the freeze-dried powder that every ampoule bottle contains the 1g magnesium gluconate, after labelling, two kinds of freeze-dried powders are packaged in the same packing box, promptly get the composition of medicine of creatine phosphate sodium freeze-dried powder pin and magnesium gluconate freeze-dried powder, the quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.078.
Can creatine phosphate sodium freeze-dried powder pin and magnesium gluconate freeze-dried powder be dissolved back mixing use respectively with an amount of water for injection during use, or successively use successively.
Embodiment 9. Creatine Phosphate Sodium magnesium chloride injection
Get one bottle of injection Creatine Phosphate Sodium magnesium chloride lyophilized injectable powder, it is dissolved, promptly obtain Creatine Phosphate Sodium magnesium chloride injection with 5ml water for injection by embodiment 1 preparation.The quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.0255.
Embodiment 10. Creatine Phosphate Sodium Magnesium Aminosuccinate glucose injections
Get one bottle of injection Creatine Phosphate Sodium Magnesium Aminosuccinate lyophilized injectable powder by embodiment 2 preparations, other gets one bottle of 250ml glucose injection (concentration is 5%), to join after the injection Creatine Phosphate Sodium Magnesium Aminosuccinate lyophilized injectable powder dissolving among the 250ml glucose injection with the 5ml glucose solution, fully mix homogeneously promptly gets Creatine Phosphate Sodium Magnesium Aminosuccinate glucose injection.The quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.042.
Embodiment 11. Creatine Phosphate Sodium magnesium gluconate oral administration solutions
Prescription: Creatine Phosphate Sodium 1g
Magnesium gluconate 1g
Sodium ethylene diamine tetracetate 0.005g
Vitamin C (making antioxidant uses) 0.01g
Sweeting agent is an amount of
Distilled water adds to 10ml
Above-mentioned component is dissolved in the water fully, and mix homogeneously filters the back and seals with glass bottle packaging to clear and bright solution, promptly get Creatine Phosphate Sodium magnesium gluconate oral administration solution, phosphoric acid creatine sodium 1g wherein, magnesium gluconate 1g, the quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.0586.
Embodiment 12. compound recipe Creatine Phosphate Sodium Aspartic Acid magnesium sheets
Prescription: Creatine Phosphate Sodium 25g
Magnesium Aminosuccinate 35g
Starch 35g
Microcrystalline Cellulose 15g
Magnesium stearate 2g
With above-mentioned material powder abundant mixing except that magnesium stearate, after the distilled water moistening, wet granulation, add magnesium stearate behind the oven dry granulate, be pressed into 100 behind the mixing, promptly get compound recipe Creatine Phosphate Sodium Aspartic Acid magnesium sheet, every phosphoric acid creatine sodium 0.25g, Magnesium Aminosuccinate 0.35g, the quality proportioning of Creatine Phosphate Sodium and magnesium elements is 1:0.1176.
Embodiment 13. compound recipe Creatine Phosphate Sodium Magnesium Aminosuccinate enteric coatel tablets
The tablet of embodiment 12 preparations is wrapped up with enteric coated solution, promptly get compound recipe Creatine Phosphate Sodium Magnesium Aminosuccinate enteric coatel tablets.Wherein, enteric coated solution can be selected the coating solution of following prescription for use: cellulose acetate-phthalate 10g, octadecanol 4.0g, diethyl phthalate 1.0ml, isopropyl alcohol 40ml, acetone 45ml.
Claims (7)
1. the composition of medicine of Creatine Phosphate Sodium and magnesium salt, wherein magnesium salt compound is selected from following compounds magnesium chloride, Magnesium Aminosuccinate, magnesium sulfate or magnesium gluconate, and the quality ratio range of Creatine Phosphate Sodium and magnesium elements is 1:0.001～5.
2. composition of medicine according to claim 1, the quality ratio range that it is characterized in that Creatine Phosphate Sodium and magnesium elements is 1:0.01～0.2.
3. composition of medicine according to claim 1, the quality ratio range that it is characterized in that Creatine Phosphate Sodium and magnesium elements is 1:0.02～0.1.
4. the composition of medicine of Creatine Phosphate Sodium and magnesium salt, wherein magnesium salt compound is selected from following compounds: the magnesium salt of Magnesium L-Asacorbic Acid 2-O-Phosphate, magnesium citrate, magnesium tartrate, magnesium carbonate, magnesium phosphate, magnesium acetate, magnesium oxalate, magnesium valproate, magnesium salicylate, Stepanol MG, amino acid whose magnesium salt, maleic acid, the magnesium salt of lactic acid, the magnesium salt of benzenesulfonic acid or the magnesium salt of fructose diphosphate, and the quality ratio range of Creatine Phosphate Sodium and magnesium elements is 1:0.001～5.
5 according to any one described composition of medicine in the claim 1 to 4, it is characterized in that Creatine Phosphate Sodium and magnesium salt are made compound preparation, and the pharmaceutical dosage form of wherein said compound preparation is injectable powder, aqueous injection, tablet, capsule, granule or oral liquid.
6. composition of medicine according to claim 5 is characterized in that can comprising pharmaceutic adjuvant in the composition of medicine.
7. according to any one described composition of medicine in the claim 1 to 4, it is characterized in that Creatine Phosphate Sodium and magnesium salt are made independent preparation respectively, and in same medicine box, the pharmaceutical dosage form of wherein said independent preparation is injectable powder, aqueous injection, tablet, capsule, granule or oral liquid with two kinds of independent preparation packings.
8. composition of medicine according to claim 7 is characterized in that can comprising pharmaceutic adjuvant in the composition of medicine.
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| ITTO20050847A1 (en) * | 2005-11-30 | 2007-06-01 | Sergey Vladimirovich Burov | COMPLEXES OF PHOSPHOCREATIN |
| CN101288649B (en) * | 2007-04-19 | 2011-01-12 | 上海慈瑞医药科技有限公司 | Preparation technique of sodium phosphocreatine powder and injection preparation |
| CN101313910B (en) * | 2007-05-31 | 2010-11-03 | 上海慈瑞医药科技有限公司 | Preparation technique for sodium phosphocreatine freeze-dried injection |
| CN101474159B (en) * | 2008-12-16 | 2010-06-23 | 海南美大制药有限公司 | Creatine phosphate sodium microballoon lyophilized preparation and method for producing the same |
| CN102210695B (en) * | 2011-04-13 | 2013-03-20 | 吉林英联生物制药股份有限公司 | Application of creatine phosphate sodium in preparing antishock medicament |
| CN104530121A (en) * | 2015-01-12 | 2015-04-22 | 精晶药业股份有限公司 | Phosphocreatine citrulline salt, and preparing method and application thereof |
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