CN108853139A

CN108853139A - The medical composition and its use of various trace elements VII

Info

Publication number: CN108853139A
Application number: CN201710321347.XA
Authority: CN
Inventors: 刘力
Original assignee: Individual
Current assignee: Individual
Priority date: 2017-05-09
Filing date: 2017-05-09
Publication date: 2018-11-23

Abstract

The present invention provides preparation and lacks for preventing or treating people and mammal various trace elements, as zinc, manganese, copper, chromium, selenium, iodine, molybdenum lack and its syndrome VII injection of various trace elements drug in application, the adverse reaction of injection is reduced, so that corresponding drug has better safety, treatment compliance etc. in treatment clinical course.

Description

The medical composition and its use of various trace elements VII

Technical field

The present invention relates to pharmaceutical technology fields, are specifically to provide prevention or treatment zinc, manganese, chromium, copper, selenium iodine, molybdenum lack The one kind of multiple micro-element injection pharmaceutical compositions and its preparation and use of weary and its syndrome etc..

Background technique

Zinc is indispensable microelement in organism, participates in the synthesis of many enzymes in vivo, has important physiology tune Save function.In tissue respiration, zinc plays an important role to the synthesis of protein, erythrocyte membrane and hematopoiesis.Zinc energy and sulphur Alcohol combines, and blocks mercaptan in conjunction with iron, inhibits the catalytic oxidation of iron and forms free radical, zinc can also inhibit the peroxide of fat Change effect, stabilizing cell membrane are allowed to have more resistance to the attack of free radical, and therefore, zinc not only grows cell but also to cell Protection be of great significance.

Chromium (III) has a variety of biochemical functions as a kind of essential trace element of life, takes part in glucide generation Thank, the processes such as lipid material metabolism, if scarce chromium will lead to the generation of many diseases in human body, chromium can be used as glucose-tolerant because The constituent of son, assist insulin play physiological function.

Copper participates in hematopoiesis and the metabolism of iron, influences the metabolism of connective tissue (such as skin, cartilage), influences collagen and bone group The formation knitted, and be the constituent of some copper enzymes.Animal is when lacking copper, the esoteric various pathologic, physiologics of machine Change in close relations with lipid peroxidation.

Trace element manganese is the constituent of a variety of enzymes, participates in energy and fat metabolism, promote bone normal growth and Development participates in the enzyme system of activation chondroitin sulfate synthesis, promotes the synthesis of sclerotin；It must can not in maintaining normal brain function It lacks, has certain relationship with intellectual development, thinking, emotion, behavior.Manganese plays the role of preventing anaemia, and manganese deficiency also can be to health Adverse effect is caused, mainly there is the following aspects：1, inhibit the synthesis of bone, the time, which has been grown, will result in cartilage development not Good, slowly, long bone is short, deformity of joint for ossification, and bone sky increases, and sclerotin hardness is declined, and toughness reduces, osteoporosis, easily In fracture.There is a serious shortage of also will affect phosphatase activity in bone, growth and development is caused to be stagnated.2, the metabolism for slowing down cell, adds The aging of fast people.3, cause neurasthenia syndrome, influence intellectual development.4, lead to the reduction of insulin synthesis and secretion, shadow Ring glycometabolism.

A large amount of survey data illustrates there there is directly the height of Se content with the disease incidence of cancer in a regional food and soil Connect relationship.Scientific research discovery, selenium have many pharmacological actions, for example strengthen immunity：Organic selenium can remove interior free yl, Vivotoxin, generation that is anti-oxidant, can effectively inhibiting lipid peroxide are excluded, blood clot is prevented, removes cholesterol, enhances people Body immunity function.Prevent diabetes：Selenium is the active constituent for constituting glutathione peroxidase, it can prevent beta Cell of islet Oxidative demage keeps its function normal, promotes sugared part metabolism, reduces blood glucose and glucose in urine, improves the symptom of diabetic.It prevents white Cataract or glaucoma：Selenium can protect retina, and the finish of reinforcing glass body improves eyesight, prevents cataract.Prevent heart and brain blood Pipe disease：Selenium is the important element for maintaining heart normal function, plays the role of protection and reparation to heart human body.Human body blood selenium water Flat reduction will lead to the hypofunction for removing free radical in vivo, hazardous material deposition caused to increase, blood pressure raising, vascular wall Thicken, blood vessel elasticity reduce, blood flow velocity it is slack-off, send oxygen function reduction, thus induce cardiovascular and cerebrovascular disease disease incidence increase, However supply Se scientific has preferable effect to prevention cardiovascular and cerebrovascular disease, hypertension, artery sclerosis etc..Trace iodine is first The essential component of shape glandular hormone (T3, T4), iodine is played by thyroxine to be promoted protein synthesis, adjusts energetic supersession and acceleration The effects of growth and development.Molybdenum is the constituent of xanthine oxidase/dehydrogenase, aldehyde oxidase and sulfite oxidase, from And know it for microelement necessary to human body and animals and plants.Studies have shown that molybdenum is there are also obvious anticaries action, molybdenum is to urinary calculus It is formed with strong inhibition effect, human body lacks molybdenum and is susceptible to suffer from kidney stone.

Generally speaking, to meeting, human nutrition needs microelement and maintenance human body biochemical reaction is normally carried out, holding machine Body eubolism and physiological function play a significant role.When microelement insufficient supply, the activity reduction or complete of enzyme can be made It loses, the synthesis and metabolism of hormone, protein, vitamin etc. will occur obstacle, organism metabolism caused to be lacked of proper care, and serious person can endanger And life.30% disease is directly caused by microelement deficiencies or imbalance.As zinc-deficiency can cause mouth, eye, anus or vulva Portion's redness, papule, eczema.For another example iron is one of the main component for constituting hemoglobin, and iron deficiency can cause hypoferric anemia.Document Report：Iron content, copper, zinc total amount are reduced in body, can be weakened immunologic mechanism (resisting the disease strength), are reduced disease resistance, are helped Long bacterium infection, and the metainfective death rate is also higher.Microelement it is disease-resistant, give protection against cancer, in terms of all also rise Very important effect.Therefore, for a long time, microelement clinically more extensive clinical application.

Nevertheless, excessive microelement is also not all right in biology, excessive microelement easily causes different diseases, including interior Parasecretion, cardiovascular disease, even causes tumour at the nervous system disease, and the patient of the different state of an illness needs different ratio The type of microelement, some need is more, and the type of some need is few, and the amount of some need is more, and the amount of some need is few, and more one Kind or it is few it is a kind of there is this qualitative difference or say in therapeutic administratp there are this qualitative difference, cause toxicity anti-in mistake multi input body It answers, this makes Rare Elements Preparations prescription have to diversification.Since microelement participates in the composition etc. of enzyme, the multiplicity of organism Property, body is very sensitive to external microelement, and the sensitivity of diversification and body also brings microelement prescription and preparation etc. On various problems (Duan Yumei, it is necessary to the effect and toxicity of minor metallic element in human body, biology notification, 2004,39 (6):25-26)。

However, multi-microelement injecta (the Trace Elements Injection in U.S. USP36 editions) is used for The supplement of microelement and the treatment of some diseases, but there are many deficiencies, above-mentioned multi-microelement injecta maintains very Under low acidity and use zinc chloride or zinc sulfate for main ingredient etc., the drug is too strong etc. there are blood vessel irritation in clinical use The situation and other potential safety factors that serious adverse reaction, toxicity are excessive and patient's compliance is poor.The prior art Component zinc sulfate in multi-microelement injecta (Trace Elements Injection) has compared with strong corrosive, skin And when contacting allergic dermatitis occurs for mucous membrane irritation, long-term steam.It is existing although Human Physiology pH commonly reaches 7.4 or so There is the pH value in technology in preparation to maintain very low level, general pH value is between 1.8~3.0 to prevent injection from quality occur Problem, strong acidity bring a degree of safety risks in the drug of different intravenously administrables is prepared and clinical vein is infused With some adverse reactions, including blood vessel irritation or phlebitis, local necrosis, patient tolerability difference or clinical unexpected etc., especially It is easily to occur during patient fluid infusion unexpected fatal once particle occurs in injection in process for preparation or in infusion process Danger, these particles may be turned a blind eye in the insufficient situation of background for naked eyes, but these are by long-standing neglect.

The multi-microelement injecta (the Trace Elements Injection in the U.S.) of the prior art also there is also The case where being not suitable for the patient of acid poisoning and renal insufficiency etc. in some cases, in feelings that are unknown in advance or being difficult to know Clinical application may bring adverse consequences under condition；{ bibliography：Document 1, Yin Peida, the morbidity of distal renal tubular acidosis Mechanism, foreign medical science (clinical practice fascicle), 12 phase of nineteen eighty-two；Document 2, Zhou Lei, etc. 12 renal tubular acidosis patient mistaken diagnosis originals Because of analysis and nursing, Chinese Quotation Analysis, 17 phases in 2005 }.

Therefore, it is necessary to reform and innovate to the multi-microelement injecta of the above-mentioned drug standards, drug is reduced not Good reaction reduces potential security risk, improves the safety and compliance and clinical treatment effect etc. of clinical application.

Summary of the invention

The present invention relates to pharmaceutical technology fields, be specifically to provide prevention or treatment zinc, manganese, copper, selenium, chromium, shortage and One kind of multiple micro-element injection pharmaceutical compositions and its preparation and use of its syndrome etc..

The pharmaceutical composition of the various trace elements of injection of the invention, a unit dose or unit formulation or list The ratio between the weight number of main ingredient component or parts by weight are in the composition of position volume：Containing 18~22 μ g of zinc (Zn), copper (Cu) 18 ~22 μ g, 3.6~4.4 μ g of manganese (Mn), 0.9~0.11 μ g of chromium (Cr), 3.6~4.4 μ g of selenium, 4.5~5.5 μ g of iodine, molybdenum 4.5~ 5.5μg；Or contain above-mentioned each main ingredient group in the composition of said one unit dose or unit formulation or unit volume 0.05~50 times of the weight number or parts by weight that divide；The composition can be infused with pharmaceutically acceptable auxiliary material or excipient composition Penetrate agent；Said one dosage unit or unit volume can be 1ml or 2ml or 2.5ml or 3ml or 5ml or 10ml or 15ml or 20ml or 40ml or 50ml or 100ml etc.；

The existence form of above-mentioned microelement is combined into acid, alkali corresponding again after can be its atom in conjunction with other atoms Pharmaceutical salts its ion or with acid, alkali be combined into corresponding pharmaceutical salts；Wherein, zinc or zinc salt are selected from zinc gluconate, the Portugal D- Grape saccharic acid zinc, lactobionic acid zinc, zinc citrate, zinc lactate or Pfansteihl zinc, zinc acetate, D- or L- or DL- L-aminobutanedioic acid zinc, sweet ammonia Sour zinc, zinc glutamate or their isomers or their hydrate or zinc ion pharmaceutically acceptable salt or theirs is different One of structure body is a variety of；

Copper or mantoquita be selected from copper chloride, copper sulphate, copper gluconate, maltonic acid copper, lactobionic acid copper, copper citrate, Copper lactate or Pfansteihl copper, copper acetate, D- or L- or DL- L-aminobutanedioic acid copper, cupric glycinate, cupric glutamate or their isomers Or their hydrate or one of bivalent cupric ion pharmaceutically acceptable salt or their chiral isomer or a variety of；

Manganese or manganese salt be selected from manganese chloride, manganese sulfate, manganese gluconate, maltonic acid manganese, lactobionic acid manganese, manganese citrate, Manganese lactate or Pfansteihl manganese, manganese acetate, D- or L- or DL- L-aminobutanedioic acid manganese, Mn-Gly, glutamic acid manganese or their isomers Or their hydrate or one of divalent manganesetion pharmaceutically acceptable salt or their chiral isomer or a variety of；

Selenium is selected from the one or more of selenous acid or sodium selenite or its hydrate or the acceptable pharmaceutical salts of selenous acid；

Chromium or chromic salts are selected from chromium chloride, chromium sulfate, chromium gluconate [(C6H11O7)₃Cr], lactobionic acid chromium, chromium citrate, D- or L- or DL- L-aminobutanedioic acid chromium, Chromic lactate, chromic acetate, glycine chromium, glutamic acid chromium or their isomers or their hydrations One of object or trivalent chromic ion pharmaceutically acceptable salt are a variety of；

Iodine is selected from one or more of potassium iodide or sodium iodide；

Molybdenum is selected from the pharmaceutically acceptable of sodium molybdate or its molybdic acid sodium hydrate, ammonium molybdate or ammonium molybdate hydrate or molybdic acid One of salt or a variety of；

Furtherly, the pharmaceutical composition of the various trace elements of injection of the invention, a unit dose or list The ratio between the weight number of main ingredient component or parts by weight are in the composition of position preparation or unit volume：Containing 18~22 μ of zinc (Zn) G, 18~22 μ g of copper (Cu), 3.6~4.4 μ g of manganese (Mn), 0.9~0.11 μ g of chromium (Cr), 3.6~4.4 μ g of selenium, 4.5~5.5 μ of iodine G, 4.5~5.5 μ g of molybdenum；Or containing above-mentioned in the composition of said one unit dose or unit formulation or unit volume 0.05~50 times of the weight number of each main ingredient component or parts by weight；The composition can be with pharmaceutically acceptable auxiliary material or figuration Agent forms injection；Said one dosage unit or unit volume can be 1ml or 2ml or 3ml or 5ml or 10ml or 20ml or 40ml or 50ml or 100ml etc.；

Wherein, zinc or zinc salt are selected from zinc gluconate, lactobionic acid zinc, zinc citrate, zinc lactate or Pfansteihl zinc, acetic acid Zinc, D- or L- or DL- L-aminobutanedioic acid zinc, glycine zine, zinc glutamate or their isomers or their hydrate or zinc from One of sub- pharmaceutically acceptable salt or their chiral isomer are a variety of；

Copper or mantoquita are selected from copper chloride, copper sulphate, copper gluconate, 1 hydrate of maltonic acid copper, lactobionic acid copper, lemon Lemon acid copper, copper lactate or Pfansteihl copper, copper acetate, D- or L- or DL- L-aminobutanedioic acid copper, cupric glycinate, cupric glutamate or they Isomers or their hydrate or one of bivalent cupric ion pharmaceutically acceptable salt or their chiral isomer Or it is a variety of；

Manganese or manganese salt are selected from manganese chloride, manganese sulfate, manganese gluconate, lactobionic acid manganese, manganese citrate, manganese lactate or Pfansteihl Manganese, manganese acetate, D- or L- or DL- L-aminobutanedioic acid manganese, Mn-Gly, glutamic acid manganese or their isomers or their hydrate Or one of divalent manganesetion pharmaceutically acceptable salt or their chiral isomer or a variety of；

Selenium is selected from the one or more of selenous acid, sodium selenite or its hydrate or the acceptable pharmaceutical salts of selenous acid；

Chromium is selected from chromium chloride, chromium sulfate, chromium gluconate [(C6H11O7)₃Cr], lactobionic acid chromium, chromium citrate, L- or D- Or DL- L-aminobutanedioic acid chromium or their hydrate, Chromic lactate, chromic acetate, glycine chromium, glutamic acid chromium or their isomers or Their hydrates or one of trivalent chromic ion pharmaceutically acceptable salt or their chiral isomer or a variety of；Iodine choosing From one or more of potassium iodide or sodium iodide；

Pharmaceutically acceptable auxiliary material or excipient are in addition to water for injection, it may include pharmaceutically acceptable amides chemical combination Object (for example niacinamide, Pyrazinamide, acetamide, urea, thiocarbamide etc.), pharmaceutically acceptable aminated compounds (for example ethylenediamine, Diethylamine, diethanol amine, triethanolamine, meglumine, Portugal's ethamine, aminoguanidine, hydroxyethyltheophylline), amino acid or its pharmaceutical salts, example Such as：D- or L- or DL-lysine or Lysine Acetate or arginine or acetic arginine or taurine or glycine or door winter ammonia Acid or Monosodium L-aspartate or D- or L- or DL-histidine or cysteine or methionine or its salt, it is pharmaceutically acceptable organic Acid or its salt, for example L-AA, citric acid or sodium citrate or lactic acid, sodium lactate, lactobionic acid, sodium lactonic, grape Saccharic acid, sodium gluconate, pharmaceutically acceptable alcohol compound, for example sorbierite or mannitol or lactitol or xylitol, D- Mannitol, D- D-sorbite or antierythrite include its hydrate or their pharmaceutically acceptable salt etc. or their hand One of property isomers is a variety of, and sorbierite includes anhydrous sorbierite or half water object of sorbierite or 1 water sorbierite or instant mountain One of pears alcohol etc. is a variety of, above-mentioned comprising its chiral isomer or its solvated compounds or its hydrate；

For pharmaceutically acceptable auxiliary material also including solubilizer (including may include surfactant), solubilizer is selected from polyoxygenated Ethylene list oleic acid sorbitan ester, Tween-80, VE succinic acid macrogol ester (vitamin E TPGS), the poly- second of glycerol- Glycol oxygroup stearate, PEG-32 glyceryl palmitostearate, lauryl sodium sulfate, Sorbitan monolaurate, Polyethylene glycol, polyethylene glycol 100-20000 (polyethylene glycol 200, polyethylene glycol 400, Macrogol 600, Macrogol 4000, Macrogol 6000, PEG 8000 etc.), polyethylene glycol-12-hydroxystearate, polyvinylpyrrolidone, polyethylene Alcohol, amino acid or its pharmaceutical salts, pharmaceutically acceptable alcohols, pharmaceutically acceptable polyalcohol, poloxamer, poloxamer188, It is azone, laurocapram, cyclodextrin or cyclodextrin pharmaceutically acceptable derivates, amides or urea and derivative, inorganic Acid is inorganic acid salt, pharmaceutically acceptable organic acid or acylate, pharmaceutically acceptable carbohydrate or sugar lime, pharmaceutically acceptable Amine etc. or their chiral isomer etc. or one of their pharmaceutically acceptable salt or a variety of；Cyclodextrin includes Alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-β-cyclodextrin etc..

One of pharmaceutically acceptable auxiliary material or excipient in addition to water for injection are a variety of in a unit dose Content in the injection of amount is selected from 0.0010~0.40g；Or it can be expressed as：It is pharmaceutically acceptable in addition to water for injection Auxiliary material or one of excipient or a variety of contents in the injection of a unit dose can be or selected from 0.0010 ~0.40g/ml.

Further, the pharmaceutical composition of various trace elements of the invention, a unit dose or unit formulation or unit The ratio between the weight number of main ingredient component or parts by weight are about in the composition of volume：Containing 18~22 μ g of zinc (Zn), copper (Cu) 18 ~22 μ g, 3.6~4.4 μ g of manganese (Mn), 0.9~0.11 μ g of chromium (Cr), 3.6~4.4 μ g of selenium, 4.5~5.5 μ g of iodine, molybdenum 4.5~ 5.5μg；Or contain above-mentioned each main ingredient group in the composition of said one unit dose or unit formulation or unit volume 0.05~50 times of the weight number or parts by weight that divide；The composition can form injection with pharmaceutically acceptable auxiliary material；On State a dosage unit or unit volume can be 1ml or 2ml or 3ml or 5ml or 10ml or 20ml or 40ml or 50ml or 100ml etc.；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit bodies The ratio between the weight number of main ingredient component or parts by weight are about in long-pending the composition：Containing 20 μ g of zinc (Zn), 20 μ g of copper (Cu), manganese (Mn) 4.0 μ g, 0.10 μ g of chromium (Cr), 4.0 μ g of selenium, 5.0 μ g of iodine, 5.0 μ g of molybdenum；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit bodies The ratio between the weight number of main ingredient component or parts by weight are about in long-pending the composition：Containing 40 μ g of zinc (Zn), 40 μ g of copper (Cu), manganese (Mn) 8.0 μ g, 0.20 μ g of chromium (Cr), 8.0 μ g of selenium, 10.0 μ g of iodine, 10.0 μ g of molybdenum；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit bodies The ratio between the weight number of main ingredient component or parts by weight are about in long-pending the composition：Containing 60 μ g of zinc (Zn), 60 μ g of copper (Cu), manganese (Mn) 12.0 μ g, 0.30 μ g of chromium (Cr), 12.0 μ g of selenium, 15.0 μ g of iodine, 15.0 μ g of molybdenum；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit bodies The ratio between the weight number of main ingredient component or parts by weight are about in long-pending the composition：Containing 100 μ g of zinc (Zn), 100 μ g of copper (Cu), manganese (Mn) 20.0 μ g, 0.50 μ g of chromium (Cr), 20.0 μ g of selenium, 25.0 μ g of iodine, 25.0 μ g of molybdenum；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit bodies The ratio between the weight number of main ingredient component or parts by weight are about in long-pending the composition：Containing 200 μ g of zinc (Zn), 200 μ g of copper (Cu), manganese (Mn) 40.0 μ g, 1.0 μ g of chromium (Cr), 40.0 μ g of selenium, 50.0 μ g of iodine, 50.0 μ g of molybdenum；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit bodies The ratio between the weight number of main ingredient component or parts by weight are about in long-pending the composition：Containing 400 μ g of zinc (Zn), 400 μ g of copper (Cu), manganese (Mn) 80.0 μ g, 2.0 μ g of chromium (Cr), 80.0 μ g of selenium, 100.0 μ g of iodine, 100.0 μ g of molybdenum；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit bodies The ratio between the weight number of main ingredient component or parts by weight are about in long-pending the composition：Containing 800 μ g of zinc (Zn), 800 μ g of copper (Cu), manganese (Mn) 160.0 μ g, 4.0 μ g of chromium (Cr), 160.0 μ g of selenium, 200.0 μ g of iodine, 200.0 μ g of molybdenum；

Wherein, zinc or zinc salt be selected from zinc gluconate or zinc gluconate hydrate, zinc gluconate (II) dihydrate, 3 hydrate of zinc gluconate, maltonic acid zinc, 3 hydrate of maltonic acid zinc, lactobionic acid zinc or lactobionic acid zinc hydrate, Zinc citrate or three zinc of citric acid or its zinc citrate hydrate zinc citrate dihydrate, Pfansteihl zinc or zinc lactate or its water Close object, 3 hydrate of Pfansteihl zinc, 3 hydrate of Pfansteihl zinc, zinc acetate, 2 hydrate of zinc acetate, D- or L- or DL- L-aminobutanedioic acid Zinc, glycine zine, zinc glutamate etc. or one or more of their isomers or its hydrate；

Copper or mantoquita are selected from copper chloride, 2 hydrate of copper chloride, copper sulphate, copper sulfate monohydrate, three brochanites, five water sulphur Sour copper, copper gluconate, 1 hydrate of copper gluconate, 1 hydrate of maltonic acid copper, 2 hydrate of copper gluconate (C₁₂H₂₂O₁₄Cu ﹒ 2H₂O), lactobionic acid copper or lactobionic acid copper hydrate, copper citrate or three bronze medal of citric acid or its copper citrate 2.5 Hydrate, copper lactate or Pfansteihl copper, cupric glycinate, cupric glutamate or their isomers or its hydrate, D- or L- or DL- L-aminobutanedioic acid copper etc. or their hydrate, copper acetate or its 1 hydrate of copper acetate [(Ac)₂Cu ﹒ H₂One or more of O]；

Manganese or manganese salt are selected from manganese chloride or its hydrate [or 2 hydrate (MnCl of 1 hydrate of manganese chloride or manganese chloride₂· 2H₂) or 4 hydrate (MnCl of manganese chloride O₂·4H₂O) or 6 hydrate of 5 hydrate of manganese chloride or manganese chloride], manganese sulfate or sulfuric acid 1 hydrate of manganese, manganese gluconate or manganese gluconate hydrate, 2 hydrate of maltonic acid manganese, lactobionic acid manganese or lactobionic acid manganese Hydrate, manganese citrate or three manganese of citric acid or manganese citrate hydrate, manganese lactate or Pfansteihl manganese or its hydrate, manganese acetate Or 4 hydrate of manganese acetate, D- or L- or DL- L-aminobutanedioic acid manganese, Mn-Gly, glutamic acid manganese etc. or their isomers or its water Close one or more of object；

Selenium is selected from but not limited to selenous acid, sodium selenite, 5 hydrate (Na of sodium selenite₂SeO₃·5H₂O), hydrogen selenite Sodium or selenous acid etc. or one or more of their acceptable pharmaceutical salts；

Chromium or chromic salts are selected from but not limited to chromium chloride, 6 hydrate of chromium chloride, chromium sulfate, 6 hydrate of chromium sulfate, glucose Sour chromium or chromium gluconate hydrate, lactobionic acid chromium or its hydrate, chromium citrate or chromium citrate hydrate, Chromic lactate or L- Chromic lactate or its hydrate, L- or D- or DL- L-aminobutanedioic acid chromium or their hydrate (such as 3 hydrate of L-ASPARTIC ACID chromium), Chromic acetate, glycine chromium, glutamic acid chromium etc. or their isomers or its hydrate or in its pharmaceutical salts it is one or more；Iodine One or more of in potassium iodide or sodium iodide or its pharmaceutical salts；

Molybdenum is selected from the pharmaceutically acceptable of sodium molybdate or its molybdic acid sodium hydrate, ammonium molybdate or ammonium molybdate hydrate or molybdic acid One of salt or a variety of；Molybdenum be relatively selected from but not limited to sodium molybdate, 2 hydrate of sodium molybdate, ammonium molybdate, 4 hydrate of ammonium molybdate, One or more of in 4 hydrate of ammonium heptamolybdate or its pharmaceutical salts；

Pharmaceutically acceptable auxiliary material or excipient may include in addition to water：Pharmaceutically acceptable amides compound (example Such as niacinamide, Pyrazinamide, acetamide, urea, thiocarbamide), pharmaceutically acceptable aminated compounds (for example ethylenediamine, diethyl Amine, diethanol amine, triethanolamine, meglumine, Portugal's ethamine, aminoguanidine, hydroxyethyltheophylline), chiral or racemization or D- or L- or The amino acid of racemization or its pharmaceutical salts salt, such as D- or L- or DL-lysine, Lysine Acetate, cysteine, methionine, smart ammonia Acid or acetic arginine or L-aminobutanedioic acid or Monosodium L-aspartate, glutamic acid, glycine, taurine, alanine, valine, bright ammonia Acid, isoleucine, serine, threonine, cysteine, cystine, methionine, asparagine, glutamine, 5- hydroxyl rely ammonia Acid, histidine, phenylalanine, tyrosine, tryptophan, 3- hydroxy-proline, 4- hydroxy-proline, proline, homocysteine, Homocystine, homoserine, ornithine, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4-Aminobutanoicacid, 2- Amino-2-methyl propionic acid, 2- methyl -3- alanine, 2,6- diaminopimelic acid, 2- amino-3-phenyl butyric, the sweet ammonia of phenyl Acid, canavanine, canaline, 4- hydroxyarginine, 4- hydroxyl ornithine, homoarginine, 4- hydroxyhomoarginine, β-rely Propylhomoserin, 2,4-diamino-butanoic, 2,3- diaminopropionic acid, 2- methyl serine etc. or trehalose are pharmaceutically acceptable organic Acid or its salt or unit or polybasic carboxylic acid or its pharmaceutical salts, for example malic acid, succinic acid, ascorbic acid, L-AA, different Ascorbic acid, sodium isoascorbate, niacin, niacinamide, pantothenic acid, sodium pantothenate, citric acid or sodium citrate or lactic acid, lactic acid Sodium, lactobionic acid, sodium lactonic, gluconic acid, sodium gluconate, pharmaceutically acceptable alcohol compound, for example maltitol, mountain Pears alcohol, mannitol, lactitol, xylitol, antierythrite etc. or its hydrate or their pharmaceutically acceptable salt or they One of chiral isomer etc. is a variety of, and sorbierite includes D- D-sorbite, anhydrous sorbierite or half water object of sorbierite or 1 water One of sorbierite or sorbitol instant etc. are a variety of, and above-mentioned includes its chiral isomer；

One of pharmaceutically acceptable auxiliary material or excipient in addition to water for injection are a variety of in a unit dose Content in the injection of amount can be or selected from 0.0010~0.40g/ml；

Or contain above-mentioned each main ingredient in the composition of said one unit dose or unit formulation or unit volume 0.25~50 times of the weight number of component or parts by weight；The composition can be formed with pharmaceutically acceptable auxiliary material or excipient Injection；Said one dosage unit or unit volume can be 1ml or 2ml or 3ml or 5ml or 10ml or 15ml or 20ml or 40ml or 50ml or 100ml etc..

Alternatively, furtherly, for the pharmaceutical composition of various trace elements of the invention, a unit dose Or the ratio between the weight number of main ingredient component or parts by weight are in the composition of unit formulation or unit volume：

Zinc gluconate or maltonic acid zinc or zinc gluconate hydrate, 2 hydrate of zinc gluconate or glucose Sour 3 hydrate of zinc or 3 hydrate 125.4357-153.3103 μ g of maltonic acid zinc (with zinc gluconate anhydride weight calculation amount) Or zinc acetate or 2 hydrate 60.3257-73.7315 μ g of zinc acetate (with 2 hydrated basis weight of zinc acetate) or L- or D- or DL- L-aminobutanedioic acid zinc or L- or D- or DL- L-aminobutanedioic acid zinc hydrate 90.724-110.8849 μ g are (in terms of L-aminobutanedioic acid zinc anhydride Weight)；Maltonic acid copper or 1 hydrate of copper gluconate or copper gluconate or 1 hydrate of maltonic acid copper or grape 2 hydrate 128.5666-157.1369 μ g of saccharic acid copper (with copper gluconate anhydride weight calculation amount) or copper sulphate or five water sulfuric acid Copper 70.7309-86.4489 μ g (with cupric sulfate pentahydrate weight calculation amount) or D- or L- or DL- L-aminobutanedioic acid copper or D- or L- or DL- Aspartic acid copper hydrate 92.9745-113.6355 μ g (with L-aminobutanedioic acid copper anhydride weight calculation amount) or 1 hydrate of copper acetate 56.5581-69.1265μg；Manganese chloride or 4 hydrate 8.2458-10.0782 μ g of 2 hydrate of manganese chloride or manganese chloride are (with chlorination Manganese weight calculation amount) or 2 hydrate of maltonic acid manganese or manganese gluconate or 2 hydrate of maltonic acid manganese or manganese gluconate 1 hydrate 11.07455-13.5356 μ g of 29.1748-35.6581 μ g (with manganese gluconate anhydride weight calculation amount) or manganese sulfate Or D- or L- or DL- L-aminobutanedioic acid manganese or D- or L- or DL- L-aminobutanedioic acid manganese hydrate 20.9113-25.5583 μ g are (with the door winter Propylhomoserin anhydrous manganese object weight calculation amount)；6 hydrate 0.4612-0.5637 μ g of chromium chloride or chromium gluconate or maltonic acid chromium or Chromium gluconate hydrate (with chromium gluconate anhydride weight calculation amount) 1.1034-1.3486 μ g or D- or L- or DL- winter ammonia Sour 3 hydrate 0.43558-0.53238 μ g of chromium or chromium citrate 1.0719-1.3102 μ g；Selenium is selected from but not limited to selenous acid 5.8792-7.1858 μ g or sodium selenite 7.9097--9.6675 μ g or 5 hydrate 11.9897-14.654 μ g of sodium selenite or It sodium hydrogen selenite 6.8817-8.411 μ g or its hydrate or the acceptable pharmaceutical salts of selenous acid but is not limited to；Iodine is selected from potassium iodide 5.8865-7.1946 μ g or sodium iodide 5.3152-6.4964 μ g；Molybdenum is selected from but not limited to 2 hydrate of sodium molybdate or sodium molybdate 11.3485-13.8704 μ g (with 2 hydrated basis weight of sodium molybdate) or four water ammonium heptamolybdate 8.2810-10.1213 μ g.

Or contain above-mentioned each main ingredient in the composition of said one unit dose or unit formulation or unit volume 0.25~50 times of the weight number of component or parts by weight；The composition can be formed with pharmaceutically acceptable auxiliary material or excipient Injection；One of pharmaceutically acceptable auxiliary material or excipient in addition to water for injection are a variety of in a unit dose Injection in content can be or be more preferably 0.010~0.30g/ml, more preferably selected from 0.0010~0.40g/ml 0.020~0.20g/ml.

This of the pharmaceutical composition of various trace elements of the invention, a unit dose or unit formulation or unit volume The ratio between the weight number of main ingredient component or parts by weight can be or be about in composition：Zinc gluconate or maltonic acid zinc or 3 hydrate of zinc gluconate hydrate, 2 hydrate of zinc gluconate or 3 hydrate of zinc gluconate or maltonic acid zinc 139.372993 μ g or 139.37299 μ g or 139.373 μ g or 139.37 μ g or 139.4 μ g or 139 μ g or 140 μ g are (with grape Saccharic acid zinc anhydride weight calculation amount) or D- or L- or DL- L-aminobutanedioic acid zinc 25.21mg or D- or L- or DL- L-aminobutanedioic acid zinc hydration Object 100.8044 μ g or 100.804 μ g or 100.8 μ g or 101 μ g or (with L-aminobutanedioic acid zinc weight calculation amount)；6 hydrate of chromium chloride 0.51244326 μ g or 0.5124433 μ g or 0.51244 μ g or 0.5125 μ g or 0.513 μ g or 0.514 μ g or 0.52 μ g or Portugal Grape saccharic acid chromium or maltonic acid chromium or chromium gluconate hydrate 1.225959689 μ g or 1.22596 μ g or 1.226 μ g or 3 hydrate of 1.227 μ g or 1.23 μ g (with chromium gluconate weight calculation amount) or 3 hydrate L-aminobutanedioic acid chromium of L-ASPARTIC ACID chromium 0.4839 μ g or 0.484 μ g or 0.48 μ g or 0.49 μ g, maltonic acid copper or copper gluconate or 1 hydrate of copper gluconate Or 2 hydrate of copper gluconate 142.8517469 μ g or 142.8517 μ g or 142.852 μ g or 142.85 μ g or 142.9 μ g or 143 μ g (with copper gluconate weight calculation amount) or cupric sulfate pentahydrate 78.589865 μ g or 78.59 μ g or 78.6 μ g or 79 μ g or D- or L- or DL- L-aminobutanedioic acid copper or L-aminobutanedioic acid copper or D- or L- or DL- L-aminobutanedioic acid copper hydrate 5.16592mg or 5.1659mg Or 5.166mg or 5.17mg (with L-aminobutanedioic acid copper weight calculation amount), 9.161995 μ g of 2 hydrate of manganese chloride or 4 hydrate of manganese chloride Or 9.162 μ g or 9.16 μ g or 9.2 μ g (with manganese chloride weight calculation amount) manganese gluconate maltonic acid manganese or or manganese gluconate 2 Hydrate 32.416454 μ g or 32.4165 μ g or 32.416 μ g or 32.417 μ g or 32.42 μ g or 32.4 μ g or 32.5 μ g or 32 μ g or 33 μ g (with manganese gluconate weight calculation amount) or 1 hydrate of manganese sulfate 12.30506 μ g or 12.305 μ g or 12.31 μ g or 12.3 μ g or D- or L- or DL- L-aminobutanedioic acid manganese or D- or L- or DL- L-aminobutanedioic acid manganese hydrate 23.2348 μ g or 23.235 μ g Or 23.24 μ g or 23.23 μ g or 23.2 μ g or 23.3 μ g ((with L-aminobutanedioic acid anhydrous manganese object weight calculation amount), 6.532516 μ of selenous acid G or 6.53252 μ g or 6.5325 μ g or 6.533 μ g or 6.53 μ g or 6.54 μ g or 6.5 μ g or 6.6 μ g or sodium selenite or sub- selenium Sour 5 hydrate of sodium, 13.321835 μ g or 13.32184 μ g or 13.3218 μ g or 13.322 μ g or 13.32 μ g or 13.34 μ g or 13.3 μ g or 13.4 μ g (with 5 hydrated basis weight of sodium selenate) or sodium hydrogen selenite 7.646342 μ g or 7.646 μ g or 7.65 μ g Or 7.7 μ g；Sodium iodide 5.90583136 μ g or 5.9058314 μ g or 5.90583 μ g or 5.9058 μ g or 5.906 μ g or 5.91 μ g Or 5.9 μ g or 6.0 μ g or potassium iodide 6.540583 μ g or 6.54058 μ g or 6.5406 μ g or 6.541 μ g or 6.54 μ g；Four water 2 water of ammonium heptamolybdate 9.201138 μ g or 9.20114 μ g or 9.2012 μ g or 9.2011 μ g or 9.201 μ g or 9.2 μ g or sodium molybdate Close object 12.60944 μ g or 12.6094 μ g or 12.609 μ g or 12.61 μ g or 12.6 μ g.Major pharmaceutical in the compositions of the present invention The rounding up for decimal point near or below number of amount can be considered as same effect, for example, zinc gluconate or D-Glucose 3 water of sour zinc or zinc gluconate hydrate, 2 hydrate of zinc gluconate or 3 hydrate of zinc gluconate or maltonic acid zinc Close object 139.372993 μ g or 139.37299 μ g or 139.373 μ g or 139.37 μ g or 139.4 μ g or 139 μ g or 140 μ g (with Zinc gluconate anhydride weight calculation amount) between be equivalent or mutual alternative, four water ammonium heptamolybdates, 9.201138 μ g Or 9.20114 be equivalent or mutual alternative between μ g or 9.2012 μ g or 9.2011 μ g or 9.201 μ g or 9.2 μ g , between 2 hydrate of sodium molybdate, 12.60944 μ g or 12.6094 μ g or 12.609 μ g or 12.61 μ g or 12.6 μ g or 13 μ g It is equivalent or mutual alternative, the similar above-mentioned processing mode of other components in the present invention.

Contain above-mentioned each main ingredient component in the composition of said one unit dose or unit formulation or unit volume Weight number or 0.25~50 times of parts by weight；The composition can be injected with pharmaceutically acceptable auxiliary material or excipient composition Agent；Said one dosage unit or unit volume can be 1ml or 2ml or 3ml or 5ml or 10ml or 20ml or 40ml or 50ml Or 100ml etc.；One of pharmaceutically acceptable auxiliary material or excipient in addition to water for injection are a variety of in a unit Content in the injection of dosage is selected from 0.0010~0.040g, is more preferably 0.0030~0.030g, and more preferably 0.0040 ~0.025g；Or it can be expressed as：One of pharmaceutically acceptable auxiliary material or excipient in addition to water for injection are more Content kind in the injection of a unit dose can be or selected from 0.0010~0.40g/ml, more preferably for 0.010~ 0.30g/ml, more preferably 0.020~0.20g/ml；Or in said one unit dose or unit formulation or unit volume 0.25~50 times of weight number or parts by weight in the composition containing above-mentioned each main ingredient component.

This of the pharmaceutical composition of various trace elements of the invention, a unit dose or unit formulation or unit volume In composition the ratio between the weight number of main ingredient component or parts by weight can be or more preferably from：2 hydrate of zinc acetate, 67.0286 μ g Or 67.029 μ g or 67.03 μ g or 67.1 μ g or 67.0 μ g, chromium gluconate or 1.226 μ g or 1.227 μ g or 1.23 μ g or chlorine Change 6 hydrate of chromium 0.5125 μ g or 0.513 μ g or 0.514 μ g or 0.52 μ g or D- or 3 hydrate of L-ASPARTIC ACID chromium or door winter 3 hydrate of propylhomoserin chromium 0.4839 μ g or 0.484 μ g or 0.49 μ g, 2 hydrate of copper gluconate or 1 hydrate of copper gluconate or Copper gluconate 142.852 μ g or 142.85 μ g or 142.9 μ g or 143 μ g (with copper gluconate weight calculation amount) or cupric sulfate pentahydrate 78.59 μ g or 78.6 μ g or 79 μ g, 1 hydrate of manganese sulfate 12.305 μ g or 12.31 μ g or 12.3 μ g or manganese gluconate 2 are hydrated Object 32.416 μ g or 32.417 μ g or 32.42 μ g or 32.4 μ g or 32.5 μ g or 32 μ g or 33 μ g (are counted weight with manganese gluconate Amount)；Selenous acid 6.5325 μ g or 6.533 μ g or 6.53 μ g or 6.54 μ g or 6.5 μ g or 6.6 μ g or sodium selenite or sodium selenite 5 hydrate 13.322 μ g or 13.32 μ g or 13.34 μ g or 13.3 μ g or 13.4 μ g (with 5 hydrated basis weight of sodium selenate) or Asia Selenic acid hydrogen sodium 7.646 μ g or 7.65 μ g or 7.7 μ g；Sodium iodide 5.9058 μ g or 5.906 μ g or 5.91 μ g or 5.9 μ g or 6.0 μ g； Four water ammonium heptamolybdates 9.2012 μ g or 9.2011 μ g or 9.201 μ g or 9.2 μ g；Or in said one unit dose or the system of unit 0.25~50 times of weight number or parts by weight in the composition of agent or unit volume containing above-mentioned each main ingredient component；The group Injection can be formed with pharmaceutically acceptable auxiliary material or excipient by closing object；Said one dosage unit or unit volume can be 1ml or 2ml or 2.5ml or 3ml or 5ml or 10ml or 20ml or 40ml or 50ml or 100ml etc..

It is further stated another way, for the medicine composition injection of various trace elements of the invention, a list In the composition of position dosage or unit formulation or unit volume the ratio between the weight number of main ingredient component or parts by weight can be or More preferably certainly：Zinc gluconate or zinc gluconate hydrate, zinc gluconate or zinc gluconate hydrate, zinc gluconate 2 hydrates or 3 hydrate of zinc gluconate 139.372993 μ g or 139.37299 μ g or 139.373 μ g or 139.37 μ g or 139.4 μ g or 139 μ g or 140 μ g (with zinc gluconate anhydride weight calculation amount) or D- or L- or DL- L-aminobutanedioic acid zinc 25.21mg Or D- or L- or DL- L-aminobutanedioic acid zinc hydrate 100.8044 μ g or 100.804 μ g or 100.8 μ g or 101 μ g or (with door winter ammonia Sour zinc weight calculation amount)；6 hydrate of chromium chloride 0.51244326 μ g or 0.5124433 μ g or 0.51244 μ g or 0.5125 μ g or 0.513 μ g or 0.514 μ g or 0.52 μ g or chromium gluconate or chromium gluconate hydrate 1.225959689 μ g or 1.22596 μ G or 1.226 μ g or 1.227 μ g or 1.23 μ g (with chromium gluconate weight calculation amount)；2 hydrate of copper gluconate or copper gluconate 1 hydrate or copper gluconate 142.852 μ g or 142.85 μ g or 142.9 μ g or 143 μ g (with copper gluconate weight calculation amount) or Cupric sulfate pentahydrate 78.59 μ g or 78.6 μ g or 79 μ g；2 hydrate of manganese chloride or 4 hydrate of manganese chloride, 9.161995 μ g or 9.162 μ g or 9.16 μ g or 9.2 μ g (with manganese chloride weight calculation amount) manganese gluconate or 2 hydrate of manganese gluconate, 32.416454 μ g or 32.4165 μ g or 32.416 μ g or 32.417 μ g or 32.42 μ g or 32.4 μ g or 32.5 μ g or 32 μ g or 33 μ g are (with gluconic acid Manganese weight calculation amount) or 1 hydrate of manganese sulfate 12.30506 μ g or 12.305 μ g or 12.31 μ g or 12.3 μ g or D- or L- or DL- Aspartic acid manganese or D- or L- or DL- L-aminobutanedioic acid manganese hydrate 23.2348 μ g or 23.235 μ g or 23.24 μ g or 23.23 μ g or 23.2 μ g or 23.3 μ g ((with L-aminobutanedioic acid anhydrous manganese object weight calculation amount)；Selenous acid 6.532516 μ g or 6.53252 μ g or 6.5325 μ g or 6.533 μ g or 6.53 μ g or 6.54 μ g or 6.5 μ g or 6.6 μ g or sodium selenite or 5 hydrate 13.321835 of sodium selenite μ g or 13.32184 μ g or 13.3218 μ g or 13.322 μ g or 13.32 μ g or 13.34 μ g or 13.3 μ g or 13.4 μ g are (with selenic acid 5 hydrated basis weight of sodium) or sodium hydrogen selenite 7.646342 μ g or 7.646 μ g or 7.65 μ g or 7.7 μ g；Sodium iodide 5.90583136 μ g or 5.9058314 μ g or 5.90583 μ g or 5.9058 μ g or 5.906 μ g or 5.91 μ g or 5.9 μ g or 6.0 μ G or potassium iodide 6.540583 μ g or 6.54058 μ g or 6.5406 μ g or 6.541 μ g or 6.54 μ g；Four water ammonium heptamolybdates 2 hydrate of 9.201138 μ g or 9.20114 μ g or 9.2012 μ g or 9.2011 μ g or 9.201 μ g or 9.2 μ g or sodium molybdate 12.60944 μ g or 12.6094 μ g or 12.609 μ g or 12.61 μ g or 12.6 μ g；Or in said one unit dose or unit 0.25~50 times of weight number or parts by weight in the composition of preparation or unit volume containing above-mentioned each main ingredient component；It should Composition can be prepared into injection with pharmaceutically acceptable auxiliary material or excipient；It is pharmaceutically acceptable in addition to water for injection Auxiliary material or one of excipient or a variety of contents in the injection of a unit dose can be or selected from 0.0010 ~0.40g/ml is more preferably 0.010~0.30g/ml, more preferably 0.020~0.20g/ml；Said one dosage unit or Unit volume can be 1ml or 2ml or 2.5ml or 3ml or 5ml or 10ml or 20ml or 40ml or 50ml or 100ml etc..

Pharmaceutically acceptable auxiliary material or excipient in addition to water can be more preferably：Lysine, the acetic acid of D- or L- or DL- relies Propylhomoserin, cysteine, methionine, arginine, acetic arginine, L-aminobutanedioic acid, Monosodium L-aspartate, glutamic acid, glycine, ox sulphur Acid, valine, threonine, cysteine, cystine, glutamine, 5- oxylysine, histidine, 3- hydroxy-proline, 4- hydroxyl Base proline, proline, ornithine, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4-Aminobutanoicacid, 2- ammonia Base -2 Methylpropionic acid, 2- methyl -3- alanine, 2,6- diaminopimelic acid, 2- amino-3-phenyl butyric, 4- hydroxyl essence ammonia Acid, 4- hydroxyl ornithine, 4- hydroxyhomoarginine, 2,4-diamino-butanoic, malic acid, succinic acid, ascorbic acid, L- Vitamin C Acid, arabo-ascorbic acid, sodium isoascorbate, niacin, niacinamide, pantothenic acid, sodium pantothenate, citric acid, sodium citrate, lactic acid, lactic acid Sodium, lactobionic acid, sodium lactonic, gluconic acid, sodium gluconate, trehalose, urea, thiocarbamide, maltitol, sorbierite, sweet dew Alcohol, lactitol, xylitol, antierythrite etc. or its hydrate or their pharmaceutically acceptable salt or their chiral isomer Deng one of or a variety of, one of above-mentioned pharmaceutically acceptable auxiliary material or excipient or a variety of in unit dose Content in injection can be or be more preferably 0.010~0.30g/ml, more preferably selected from 0.0010~0.40g/ml 0.020~0.20g/ml.

It should be pointed out that needing one unit of weight ratio of weighed main ingredient component in the composition in preparation preparation The case where weight of the component of dosage is usually big, and weight data is saved in the presence of foundation ratio enlargement and/or slightly or equivalent is replaced, It in the present invention, can be on scale or accurate according to the quantitative relation between the molecular weight or quality of each component itself Extended on to the digit of different decimal points, or according to the regular further analogy that rounds up, for example zinc gluconate or Zinc gluconate hydrate 139.372993 μ g or 139.37299 μ g or 139.373 μ g or 139.37 μ g or 139.4 μ g or 139 μ Between g or 140 μ g (with zinc gluconate anhydride weight calculation amount), 142.852 μ g of copper gluconate or gluconic acid copper hydrate Or 142.85 between μ g or 142.9 μ g or 143 μ g (with copper gluconate weight calculation amount)；Manganese gluconate or manganese gluconate hydration Object 32.416454 μ g or 32.4165 μ g or 32.416 μ g or 32.417 μ g or 32.42 μ g or 32.4 μ g or 32.5 μ g or 32 μ g or Between 33 μ g (with manganese gluconate weight calculation amount)；6 hydrate of chromium chloride 0.51244326 μ g or 0.5124433 μ g or 0.51244 μ Between g or 0.5125 μ g or 0.513 μ g or 0.514 μ g or 0.52 μ g, sodium iodide 5.90583136 μ g or 5.9058314 μ g or Weight between 5.90583 μ g or 5.9058 μ g or 5.906 μ g or 5.91 μ g or 5.9 μ g or 6.0 μ g is equal effect or can phase Mutual equivalent replacement, it is omitted or is accepted or rejected because of effective digital difference；Other or other components can and so on, this The effective digital of main ingredient or auxiliary material accepts or rejects mode in other compositions of invention or principle is also identical with this.

It is said differently, the pharmaceutical composition of various trace elements, a unit dose or unit formulation or unit volume The composition in main ingredient component weight number or the ratio between parts by weight be or more preferably from：Zinc gluconate or zinc gluconate Hydrate, 2 hydrate of zinc gluconate or 3 hydrate of zinc gluconate 139.372993 μ g or 139.37299 μ g or 139.373 μ g or 139.37 μ g or 139.4 μ g or 139 μ g or 140 μ g (with zinc gluconate anhydride weight calculation amount)；6 hydrate of chromium chloride 0.51244326 μ g or 0.5124433 μ g or 0.51244 μ g or 0.5125 μ g or 0.513 μ g or 0.514 μ g or 0.52 μ g or Portugal Grape saccharic acid chromium or chromium gluconate hydrate 1.225959689 μ g or 1.22596 μ g or 1.226 μ g or 1.227 μ g or 1.23 μ g (with chromium gluconate weight calculation amount)；142.852 μ of 2 hydrate of copper gluconate or 1 hydrate of copper gluconate or copper gluconate G or 142.85 μ g or 142.9 μ g or 143 μ g (with copper gluconate weight calculation amount)；2 hydrate of manganese gluconate or manganese gluconate 32.416454 μ g or 32.4165 μ g or 32.416 μ g or 32.417 μ g or 32.42 μ g or 32.4 μ g or 32.5 μ g or 32 μ g or 33 μ g (with manganese gluconate weight calculation amount)；Selenous acid 6.532516 μ g or 6.53252 μ g or 6.5325 μ g or 6.533 μ g or 6.53 μ g Or 6.54 μ g or 6.5 μ g or 6.6 μ g or sodium selenite or 5 hydrate of sodium selenite 13.321835 μ g or 13.32184 μ g or 13.3218 μ g or 13.322 μ g or 13.32 μ g or 13.34 μ g or 13.3 μ g or 13.4 μ g (with 5 hydrated basis weight of sodium selenate) Or sodium hydrogen selenite 7.646342 μ g or 7.646 μ g or 7.65 μ g or 7.7 μ g；Sodium iodide 5.90583136 μ g or 5.9058314 μ G or 5.90583 μ g or 5.9058 μ g or 5.906 μ g or 5.91 μ g or 5.9 μ g or 6.0 μ g；Four water ammonium heptamolybdates, 9.201138 μ g Or 9.20114 μ g or 9.2012 μ g or 9.2011 μ g or 9.201 μ g or 9.2 μ g or 2 hydrate of sodium molybdate, 12.60944 μ g or 12.6094 μ g or 12.609 μ g or 12.61 μ g or 12.6 μ g；In said one unit dose or unit formulation or unit volume 0.20~50 times of weight number or parts by weight in the composition containing above-mentioned each main ingredient component；The composition can be with other medicines Acceptable auxiliary material or excipient collectively constitute injection on；Pharmaceutically acceptable auxiliary material or tax in addition to water for injection One of shape agent or a variety of contents in the injection of a unit dose are selected from 0.0010~0.040g, more preferably for 0.0030~0.030g, more preferably 0.0040~0.025g；Or it can be expressed as：Can pharmaceutically connect in addition to water for injection One of auxiliary material or excipient for receiving or a variety of contents in the injection of a unit dose taken water as a solvent can be with It is more preferably 0.010~0.30g/ml for 0.0010~0.40g/ml, more preferably 0.020~0.20g/ml；It can pharmaceutically connect The auxiliary material or excipient received in addition to water can be more preferably：D- or L- or DL-lysine, Lysine Acetate, cysteine, egg ammonia Acid, arginine, acetic arginine, L-aminobutanedioic acid, Monosodium L-aspartate, glutamic acid, glycine, taurine, valine, threonine, Cysteine, cystine, glutamine, 5- oxylysine, histidine, 3- hydroxy-proline, 4- hydroxy-proline, proline, Ornithine, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4-Aminobutanoicacid, 2- amino-2-methyl propionic acid, 2- Methyl -3- alanine, 2,6- diaminopimelic acid, 2- amino-3-phenyl butyric, 4- hydroxyarginine, 4- hydroxyl ornithine, It is 4- hydroxyhomoarginine, 2,4-diamino-butanoic, malic acid, succinic acid, ascorbic acid, L-AA, arabo-ascorbic acid, different Sodium ascorbate, niacin, niacinamide, pantothenic acid, sodium pantothenate, citric acid, sodium citrate, lactic acid, sodium lactate, lactobionic acid, lactobionic acid Sodium, gluconic acid, sodium gluconate, trehalose, urea, thiocarbamide, maltitol, sorbierite, mannitol, lactitol, xylitol, One of antierythrite etc. or its hydrate or their pharmaceutically acceptable salt or their chiral isomer etc. are a variety of； Said one dosage unit or unit volume can be 1ml or 2ml or 2.5ml or 3ml or 5ml or 10ml or 20ml or 40ml or 50ml or 100ml etc..

In addition, the pharmaceutical composition of various trace elements of the invention can also be expressed as, 100 or 1,000 unit doses or In the composition of unit formulation or unit volume the ratio between the weight number of main ingredient component or parts by weight can be or more preferably from：

3 hydrate of zinc gluconate or zinc gluconate hydrate, 2 hydrate of zinc gluconate or zinc gluconate 139.372993 μ g or 139.37299 μ g or 139.373 μ g or 139.37 μ g or 139.4 μ g or 139 μ g or 140 μ g are (with grape Saccharic acid zinc anhydride weight calculation amount), 6 hydrate of chromium chloride 0.51244326 μ g or 0.5124433 μ g or 0.51244 μ g or 0.5125 μ g or 0.513 μ g or 0.514 μ g or 0.52 μ g or chromium gluconate or 1.225959689 μ g of chromium gluconate hydrate or 1.22596 μ g or 1.226 μ g or 1.227 μ g or 1.23 μ g (with chromium gluconate weight calculation amount)；2 hydrate of copper gluconate or Portugal 1 hydrate of grape saccharic acid copper or copper gluconate 142.852 μ g or 142.85 μ g or 142.9 μ g or 143 μ g are (in terms of copper gluconate Weight), manganese gluconate or 2 hydrate of manganese gluconate 32.416454 μ g or 32.4165 μ g or 32.416 μ g or 32.417 μ g Or 32.42 μ g or 32.4 μ g or 32.5 μ g or 32 μ g or 33 μ g (with manganese gluconate weight calculation amount), 6.532516 μ g of selenous acid or 6.53252 μ g or 6.5325 μ g or 6.533 μ g or 6.53 μ g or 6.54 μ g or 6.5 μ g or 6.6 μ g or sodium selenite or selenous acid 5 hydrate of sodium 13.321835 μ g or 13.32184 μ g or 13.3218 μ g or 13.322 μ g or 13.32 μ g or 13.34 μ g or 13.3 μ g or 13.4 μ g (with 5 hydrated basis weight of sodium selenate)；Sodium iodide 5.9058 μ g or 5.906 μ g or 5.91 μ g or 5.9 μ g or 6.0 μg；Four water ammonium heptamolybdates 9.201138 μ g or 9.20114 μ g or 9.2012 μ g or 9.2011 μ g or 9.201 μ g or 9.2 μ g or molybdenum Sour 2 hydrate of sodium, 12.60944 μ g or 12.6094 μ g or 12.609 μ g or 12.61 μ g or 12.6 μ g；

Above-mentioned the composition can form injection with pharmaceutically acceptable auxiliary material or excipient；In addition to water for injection One of pharmaceutically acceptable auxiliary material or excipient or a variety of contents in the injection of a unit dose are selected from 0.0010~0.040g is more preferably 0.0030~0.030g, more preferably 0.0040~0.025g；Or it can be expressed as：It removes One of pharmaceutically acceptable auxiliary material or excipient except water for injection or it is a variety of in unit dose with water It can be for the content in the injection of solution or be selected from 0.0010~0.40g/ml, be more preferably 0.010~0.30g/ml, more Preferably 0.020~0.20g/ml；

VII injection of various trace elements of the invention and its preparation process：

Method one, step 1 use the pharmaceutical salts of zinc, the pharmaceutical salts of manganese, the pharmaceutical salts of copper, the pharmaceutical salts of chromium in right amount one by one Water for injection dissolution or with the dissolution of the water for injection of suitable acidification；Step 2, by selenous acid or its pharmaceutical salts, molybdenum it is medicinal Salt, iodine pharmaceutical salts dissolved with suitable water for injection；Each step solution is uniformly mixed by step 3, then with can pharmaceutically connect The pH adjusting agent received adjusts pH value between 3.8~5.5, and more preferably pH value is between 4.0~4.8 or ultrafiltration membrane removes heat source, Or add active carbon decoloring, and decarburization being filtered, then moisturizing constant volume, refined filtration is examined, and it is filling, it seals, sterilizes, pack, examine.Wherein, The upper acceptable pH adjusting agent of the injection water system medication of acidification is acidified, and pH is usually between 3.6-5.0.

Or method two, step 1, the pharmaceutical salts of molybdenum or other auxiliary materials or the suitable water for injection of excipient dissolved；Step Rapid 2, by manganese ion pharmaceutically acceptable salt, copper ion pharmaceutically acceptable salt respectively with suitable water for injection dissolution or It is dissolved with the water for injection of suitable acidification；Step 3, by the water for injection of the suitable acidification of the acceptable pharmaceutical salts of zinc ion Dissolution；Step 4 dissolves chromium ion pharmaceutically acceptable salt with suitable water for injection or with the injection of suitable acidification Water dissolution；Step 5 dissolves selenous acid or its pharmaceutical salts, the pharmaceutical salts of iodine with suitable water for injection respectively；Step 6 will walk Rapid 2 solution is uniformly mixed with the solution of step 3 respectively；Step 7 mixes the solution of step 1 and the solution of step 4；Step 8, the solution of step 6 and the solution of step 7 are mixed, is then existed with the pH value that pharmaceutically acceptable pH adjusting agent adjusts solution Between 3.8~5.5, preferable ph is between 4.0~4.8；Step 9 adds proper amount of active carbon to decolourize in solution, filters decarburization, or Filtering with microporous membrane, or retention relative molecular mass is used to mix for 0.3 ten thousand to 300,000 membrane filtration or above-mentioned filter method It uses, it is preferred to use the ultrafiltration membrane of retention relative molecular mass 3000~60000 removes remaining heat source, moisturizing constant volume；0.20- 0.45 μm of miillpore filter or ultrafiltration etc. carry out refined filtration, examine, filling, seal, and sterilize, and pack, and examine.Wherein, the injection of acidification It is acidified with water system with pharmaceutically acceptable pH adjusting agent, pH is usually between 3.6-5.0；

Or method three, the pharmaceutical salts of zinc, the pharmaceutical salts of manganese, the pharmaceutical salts of copper, the pharmaceutical salts of chromium are used into suitable note one by one Then plus selenous acid or its pharmaceutical salts, the pharmaceutical salts of molybdenum, iodine it penetrates and is dissolved with water or with the dissolution of the water for injection of suitable acidification, Pharmaceutical salts, so that dissolution；PH value is adjusted between 3.8~5.2 with pharmaceutically acceptable pH adjusting agent again, and more preferably pH value exists Between 4.0~4.8, ultrafiltration membrane removes heat source, then moisturizing constant volume, refined filtration, examines, filling, seals, and sterilizes, and packs, and examines. Wherein, the upper acceptable pH adjusting agent of the injection water system medication of acidification is acidified, and pH is usually between 3.6-5.0.

Different modes can be used in step in above-mentioned each method, in the case where not violating pharmaceutical principle, intersection or interaction are replaced Change use.

Pharmaceutical composition in the present invention can form injection with pharmaceutically acceptable auxiliary material or excipient；Except injection One of pharmaceutically acceptable auxiliary material or excipient except water or a variety of containing in the injection of a unit dose Amount is selected from 0.0010~0.40g/ml, is more preferably 0.010~0.30g/ml, more preferably 0.020~0.20g/ml；Or it can be with It is expressed as：One of pharmaceutically acceptable auxiliary material or excipient in addition to water for injection are a variety of in a unit dose Can be using water as the content in the injection of solution or selected from 0.0010~0.40g/ml, more preferably for 0.010~ 0.30g/ml, more preferably 0.020~0.20g/ml.

For the drug combination injection in invention, the pH adjusting agent pharmaceutically received is in every 1000ml of the invention Injection can contain 0.0001-200.00 grams or more, and used pH adjusting agent is calculated with its effective component or molecular formula Its weight is calculated corresponding volume according to data such as concentration or density or is calculated with molar concentration (M) or equivalent concentration (N). Used pH adjusting agent is added in the solution of composition in form of an aqueous solutions during preparing preparation.When using alkali Property solution come when adjusting pH value (such as sodium hydroxide, trisodium citrate, sodium gluconate it is one or more), in adjustment process In, or it can be adjusted jointly with the mixed solution of soda acid, then adjusted with another kind, it can also be after a kind of excess with pharmaceutically acceptable Acid solution adjusts back (for example, acetic acid, lactic acid, citric acid, gluconic acid solution), to control a suitable pH value, otherwise also So.

Pharmaceutically acceptable pH adjusting agent can be pharmaceutically acceptable inorganic acid or organic acid, inorganic base or organic Alkali is also possible to the lewis acid or alkali of broad sense, can be acetic acid and acetate, such as acetic acid containing one or several kinds Sodium etc., lactic acid and lactic acid pharmaceutical salts, citric acid pharmaceutical salts, sodium hydroxide, trihydroxy aminomethane, diethanol amine, ethanol amine, two Isopropanolamine, 2- amino -2- (methylol) 1,3-PD amine, N- methyl glucose amine and their salt, multi-hydroxy carboxy acid and Pharmaceutical salts, such as glucuronic acid, gluconic acid, lactobionic acid, malic acid, threonic acid, glucoheptonic acid, amino acid or their pharmacy One of upper acceptable salt etc. is several.

The pharmaceutically acceptable antioxidant and stabilizer contained in pharmaceutical compositions of the invention can be sulfurous acid And its salt, bisulfites, pyrosulfite, dithionite, thioacetic acid and its pharmaceutical salts, thiolactic acid and its medicinal Salt, thio-2 acid and salt, amino acid and its pharmaceutical salts；Tartaric acid, sorbic acid or its pharmaceutical salts, nitrate, acetic acid are medicinal Salt, citrate, EDTA and edta salt, such as EDETATE SODIUM, tetra- sodium of EDTA, Ca-EDTA sodium salt (including sodium ethylene diamine tetracetate 2 hydrate of calcium or sodium ethylene diamine tetracetate calcium, 4 hydrate of sodium ethylene diamine tetracetate calcium), N- bis- (2- ethoxy) glycine, One of maltitol, xylitol, sorbierite, mannitol, taurine, amino acid or its pharmaceutically acceptable salt etc. or It is several；The salt of above-mentioned substance selects its pharmaceutically acceptable salt.

In the injection of pharmaceutical compositions of the invention can containing pharmaceutically preservative or bacteriostatic agent, as sorbic acid or its One or more of pharmaceutical salts, methylparaben, benzyl alcohol, benzyl carbinol, anesin, Benzethonium etc..

In the injection of pharmaceutical composition of the present invention, pharmaceutically acceptable isotonic regulator can be used, pharmaceutically Acceptable isotonic regulator can be glucose, fructose, maltitol, lactitol, xylitol, sorbierite, mannitol, red moss One or more of sugar alcohol, inverted sugar, dextran, sodium lactate or sodium lactonic, gluconic acid or sodium gluconate etc..

It goes heat source and degerming mode to can be addition in injection preparation and removes heat source with the active carbon of liquid measure 0.005~1%, Filtering with microporous membrane or degerming and/or pressure sterilizing can also use heat sterilization, remove heat source.In hyperfiltration process, ultrafilter can Flat, rolling, tubular type, hollow fiber form or circle boxlike etc., more preferably rolling and hollow fiber form ultrafilter are selected, using cutting After staying the filter membrane that relative molecular mass is 50,000 to 300,000 to remove most of heat generation substance and bacterium, then using retention phase to point The ultrafiltration membrane of protonatomic mass 3000~60000 removes remaining heat source, the preferably ultrafiltration membrane of relative molecular mass 6000~30000.

Following two experiment embodies the improved advantage of specific aim of the present invention

One, pharmaceutical composition of the invention is to mouse writhing reaction experiment

1, test objective

The power of multi-microelement injecta pharmaceutical composition writhing response after intraperitoneal administration of the invention is observed, with Investigate the degree of the adverse reaction of different groups of other pharmaceutical compositions.

2, animal subject：Adult healthy white mouse, half male and half female, weight 18-22g.

3, test method：Mouse writhing method

Mouse 60, half male and half female, fasting (can't help water) 12h is randomly divided into 6 groups, respectively vehicle control group, Duo Zhongwei Secondary element primary standard medicine composition injection control group (table 1, multi-microelement injecta, the Trace of U.S. USP Elements Injection) and (referring to 1 method of embodiment program prepare), example 1 group, 5 groups of embodiment, 8 groups of embodiment and 18 groups of embodiment.Administration mode is intraperitoneal injection, and dosage is 0.2ml respectively, gives vehicle control group respectively The multi-microelement injecta control group solution (Trace in table 1 is injected intraperitoneally in 5% injection of 0.2ml glucose Elements Injection control group solution) 0.2ml, after embodiment solution 0.2ml is injected intraperitoneally in remaining each group, observation administration Mouse generates the number that writhing response occurs in 15min afterwards.

4, as a result, it has been found that, vehicle control group does not generate writhing response, and the note of the various trace elements in the following table 1 is injected intraperitoneally Penetrate liquid (Trace Elements Injection) control group generate writhing response number respectively may be about 1.7 times of embodiment 1, 2.3 times of 5 groups of embodiment, 2.5 times of 8 groups of embodiment, 2.1 times or more of 18 groups of embodiment, the results showed that, medicine of the invention The adverse reaction degree of compositions is significantly less than control group.

1. various trace elements of table, VII medicine composition injection control group

Two, medicine composition injection of the invention and control group solution ph stability experiment

Laboratory sample：Control group solution：Table 1, multi-microelement injecta, the Trace of United States Pharmacopeia USP36 Elements Injection is prepared according to the method mentioned in component in table 1 and mouse writhing reaction experiment, then, respectively Take 10ml sample to be placed in two clean cillin bottles, respectively with the sodium hydroxide solution of 1M adjust the pH value of above-mentioned solution to 4.4, it then seals, concussion mixing, is protected from light standing storage 12h, as a result, it has been found that two samples are heavy in the presence of being visually evident that It forms sediment；

Experimental group solution：The sample 20ml that respectively prepared by Example 4,14 method of embodiment, 15 method of embodiment is respectively placed in In two clean cillin bottles, then the pH value for adjusting above-mentioned solution with the sodium hydroxide solution of 1M respectively is sealed, is shaken to 4.4 Mixing is swung, standing storage 12h is protected from light, discovery has no precipitating and generates, and still keeps solution state.

Furtherly, the present invention provides improved or more have the multi-microelement injecta pharmaceutical composition of advantage, The present invention also embodies further advantage simultaneously：1, eliminate that corrosivity is strong or the zinc chloride or zinc sulfate of strong toxicity, so that this The adverse reaction of the composition of invention reduces, the energy compared with the composition of the big zinc chloride of prior art middle dosage or zinc sulfate etc. The incidence for reducing toxic reaction, the irritation and local necrosis for mitigating or reducing intravenously administrable occur, and improve the safety of medication Property, be conducive to improve patient to the compliance of drug；2, after former composition prescription is removed in optimization, relative to original prescription, facilitate The whole of composition injection acidity is promoted, so that disposing with other present or future listing drugs in clinical medicine In journey when mixed preparing injection, the pH value difference between different pharmaceutical preparation is reduced, it is fatal with liquid process to reduce injection Foreign matter or precipitating generate, the safety and validity and patient when being conducive to stability and clinical use after solution is prepared Tolerance；3, new selection is provided for having occurred or the patient of acid poisoning easily occurring, or reduce potential adverse reaction, improve Clinical clinical safety etc..

VII injection pharmaceutical composition of various trace elements of the invention is suitable for preparation for providing prevention or treatment Application in the multi-microelement injecta drug of zinc, chromium, manganese, copper, selenium, iodine, molybdenum shortage and its syndrome etc., so that product The tolerance or new adaptation population or better specific aim and better clinical safety etc. having been had more in clinical use； It is more suitable for the patient or children of acid poisoning etc..

Specific embodiment

In addition in embodiment and it is indicated otherwise when, all numerical value used in specification and claims should be by It is interpreted as being modified in all examples with term " about ", therefore, unless the contrary indication, this specification and appended The numerical parameter gone out given in claims is approximation, can the required property according to sought by through present disclosure Matter and change, at least, and not be intended to limit the application of doctrine of equivalents scope of the claims, each numerical parameter is taken an examination The number and routine for considering effective digital round up method to explain.

Although the numberical range and parameter that set the wide scope of disclosure are approximations.But institute in a particular embodiment The numerical value provided is reported as precisely as possible, and any number substantially includes certain by finding in their own test The error that standard deviation is necessarily led to.

It should be pointed out that unless in text clearly in addition explanation, used in this specification and the appended claims Singular "one", "an" and "the" include referring to thing plural form, so, such as.If referred to containing " one It include the mixture of two or more compounds when the composition of kind compound ", it is further noted that unless clear herein In addition ground illustrates that term "or" generally includes "and/or".

Pharmaceutical composition

" pharmaceutical composition " used herein refers to the composition of drug, and the pharmaceutical composition can contain at least one Pharmaceutically acceptable carrier.

" pharmaceutically acceptable excipient " used herein refers to the medicine for the compound administration for being suitable for occasionally providing herein With carrier or solvent comprising well known to a person skilled in the art any examples of such carriers for being suitable for specific administration mode.

In the preparation process of various embodiments of the present invention, the case where the prescription of embodiment has limited the title of each component Under, for simplicity for each component in prescription, the simplification appellation of under type such as can be carried out or the property omitted address for example can be with 3 hydrate of zinc gluconate in prescription is referred to as zinc gluconate hydrate or zinc gluconate；3 water of maltonic acid zinc It closes object and is referred to as 3 hydrate of zinc gluconate or zinc gluconate；Or 1 hydrate of copper gluconate is referred to as gluconic acid copper water Close object or copper gluconate；Or 6 hydrate of chromium chloride is referred to as chromium chloride hydrate or chromium chloride；Or manganese sulfate 1 hydrate letter Referred to as manganese sulfate hydrate or manganese sulfate；Or sodium selenite pentahydrate is referred to as sodium selenite；L-ASPARTIC ACID manganese hydrate Referred to as L-aminobutanedioic acid manganese hydrate or L-ASPARTIC ACID manganese or L-aminobutanedioic acid manganese etc., the rest may be inferred for other components.

In order to further appreciate that the present invention, the preferred embodiment of the invention is described below with reference to embodiment, still It should be appreciated that these descriptions are only further explanation the features and advantages of the present invention, rather than to the claims in the present invention Limitation.

Illustrate effect of the invention with specific embodiment below, but protection scope of the present invention is not by the limit of following embodiment System.

Specific embodiment

The preparation of 1 various trace elements of embodiment, VII drug combination injection

Prescription：Zinc gluconate hydrate 1393.8mg (weight is in terms of zinc gluconate anhydride)

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by four water ammonium heptamolybdates of recipe quantity, sodium iodide, Sodium gluconate, sorbierite, taurine, sodium pantothenate proper amount of fresh water for injection stirring and dissolving, with gluconic acid solution will It is acidified pH value to 3.8；6 hydrate of chromium chloride, cupric sulfate pentahydrate, manganese chloride are acidified with gluconic acid solution by step 2 respectively Fresh water for injection stirring and dissolving makes solution keep clarifying and being mixed evenly；Step 3, the acidification of zinc gluconate hydrate Suitable water for injection dissolution, make solution keep clarification；Step 4 stirs 5 hydrate of sodium selenite with suitable water for injection Mix dissolution；Step 5 mixes the solution of step 3 and the solution of step 1；Step 6, by the solution of the solution of step 2 and step 4 It is uniformly mixed, then is mixed with the solution of step 5, then adjust pH value with suitable 2M gluconic acid solution and 2M glucose sodium solution To 3.9, benefit adds to the full amount of water for injection, and stirs evenly, and 0.22 μm of miillpore filter circulating filtration；Then, then it is micro- with 0.22 μm Hole membrane filtration, filtrate press the encapsulating of 5ml/ branch, 121 DEG C of 15min sterilizing to get.

It takes suitable above-mentioned sample to be protected from light and is placed in 30 DEG C, placed 6 months in the environment of relative humidity 75% ± 5%, solution Keep clear and bright, the pH value for measuring solution is 3.9.

The preparation of 2 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1559.04mg of zinc gluconate, 6 hydrate 5.2mg of chromium chloride, cupric sulfate pentahydrate 785.9mg, 1 hydrate 123.1mg of manganese sulfate, 5 hydrate 133.4mg of sodium selenite, potassium iodide 65.4mg, four water ammonium heptamolybdate 92mg, ox Sulfonic acid 50g, D-glucitol 30g, sodium gluconate 10g, L- sodium pantothenate 3g, 2M gluconic acid solution and 2M sodium lactate solution are suitable Amount, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by four water ammonium heptamolybdates of recipe quantity, potassium iodide, Taurine, sodium gluconate, sorbierite, L- sodium pantothenate proper amount of fresh water for injection stirring and dissolving, by gluconic acid solution PH value is acidified to 3.8；6 hydrate of chromium chloride, cupric sulfate pentahydrate, 1 hydrate of manganese sulfate are used gluconic acid molten by step 2 respectively Suitable water for injection stirring and dissolving of liquid acidification, makes solution keep clarification；Step 3,3 hydrate of zinc gluconate are new with acidification Fresh suitable water for injection dissolution；Step 4, the water for injection stirring and dissolving that 5 hydrate of sodium selenite is used to proper amount of fresh respectively； Step 5 mixes the solution of step 3 and the solution of step 1；It is step 6, the solution of step 2 is successively abundant with the solution of step 4 It is uniformly mixed, then is mixed with the solution of step 5, then adjust pH value with suitable gluconic acid solution and sodium gluconate solution To 3.8, benefit adds to the full amount of water for injection, and stirs evenly simultaneously 0.22 μm of miillpore filter of circulating filtration；Then, using retention phase to point The ultrafiltration membrance filter of protonatomic mass 6000-20000, filtrate press the encapsulating of 10ml/ branch, 121 DEG C of 15min sterilizing to get.

The preparation of 3 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1559.1mg of zinc gluconate, 6 hydrate 5.2mg of chromium chloride, cupric sulfate pentahydrate 785.9mg, 1 hydrate 123.1mg of manganese sulfate, 5 hydrate 133.4mg of sodium selenite, sodium iodide 59.1mg, four water ammonium heptamolybdate 92mg, ox Sulfonic acid 30g, sorbierite 20g, glycine 20g, sodium gluconate 12g, 2M lactose acid solution and 1M sodium hydroxide solution be appropriate, 5M Appropriate sodium hydroxide solution, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Supplementary material is weighed or prepared by prescription, and each component of recipe quantity is successively used proper amount of fresh by step 1 Water for injection stirring and dissolving, then each solution is uniformly mixed, then with suitable lactose acid solution and sodium hydroxide solution tune PH value is saved to 3.9, benefit adds to the full amount of water for injection, and stirs evenly simultaneously 0.22 μm of miillpore filter of circulating filtration；Then, using retention The ultrafiltration membrance filter of relative molecular mass 8000-20000, filtrate presses 1ml/ branch, 2ml/ branch and 10ml/ branch encapsulating respectively, by three The injection of kind of specification respectively at 121 DEG C of 15min sterilizings to get.It takes suitable above-mentioned sample to be protected from light and is placed in 30 DEG C, relative humidity It is placed 6 months in the environment of 75% ± 5%, solution keeps clear and bright, and the pH value for measuring solution is 3.9.

The preparation of 4 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1393.73mg of zinc gluconate (weight is in terms of zinc gluconate anhydride), chromium chloride 6 are hydrated Object 5.2mg, 1 hydrate 1428.5mg of copper gluconate (in terms of copper gluconate anhydride), 2 hydrate of manganese gluconate 324.2mg (weight is in terms of manganese gluconate anhydride), 5 hydrate 133.4mg of sodium selenite, sodium iodide 59.1mg, four water seven Ammonium molybdate 92mg, sorbierite 40g, taurine 80g, sodium gluconate 10g, 3M gluconic acid solution and 2M sodium gluconate are water-soluble Appropriate liquid, appropriate water for injection add to full dose 10000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by four water ammonium heptamolybdates of recipe quantity, sodium iodide, Gluconic acid solution is acidified pH value to 4.3 by the water for injection stirring and dissolving of sorbierite, sodium gluconate proper amount of fresh；Step Rapid 2,6 hydrate of chromium chloride, 1 hydrate of copper gluconate, 2 hydrate of manganese gluconate, zinc gluconate are used into grape respectively Sugar acid solution is acidified fresh water for injection stirring and dissolving；The water for injection of step 3,5 hydrate proper amount of fresh of sodium selenite Stirring and dissolving；Each solution is uniformly mixed by step 4, is then adjusted with suitable gluconic acid solution and sodium gluconate solution To 4.3, benefit adds to the full amount of water for injection pH value, stirs evenly and with 0.22 μm of miillpore filter circulating filtration；Then, using retention The ultrafiltration membrance filter of relative molecular mass 8000-20000,5ml/ branch encapsulating, 121 DEG C of 15min sterilizing to get.It takes on suitable It states sample and is protected from light and be placed in 30 DEG C, placed 6 months in the environment of relative humidity 75% ± 5%, solution keeps clear and bright, measures solution PH value is 4.3.

The preparation of 5 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1393.7mg of maltonic acid zinc (with zinc gluconate anhydride weight calculation amount), 6 water of chromium chloride Close object 5.2mg, 1 hydrate 1428.5mg of maltonic acid copper (with copper gluconate anhydride weight calculation amount), maltonic acid manganese 2 Hydrate 324.2mg (in terms of manganese gluconate anhydride), 5 hydrate 133.4mg of sodium selenite, sodium iodide 59.1mg, four water Ammonium heptamolybdate 92mg, sorbierite 10g, taurine 60g, L-thiamine 40g, 2M gluconic acid solution and 2M sodium gluconate solution In right amount, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by the sorbierite of recipe quantity, taurine, L- tea ammonia The water for injection stirring and dissolving of sour proper amount of fresh, with the pH value of gluconic acid solution souring soln about to 4.4；Step 2, grape 3 hydrate of saccharic acid zinc, 6 hydrate of chromium chloride, 1 hydrate of copper gluconate, 2 hydrate of manganese gluconate use gluconic acid respectively Solution is acidified fresh water for injection stirring and dissolving；Step 3 uses 5 hydrate of sodium selenite, sodium iodide, four water ammonium heptamolybdates The water for injection stirring and dissolving of proper amount of fresh；Each solution is sufficiently mixed uniformly by step 4, then molten with suitable gluconic acid Liquid and sodium gluconate solution adjust pH value about to 4.4, and benefit adds to the full amount of water for injection, and stirs evenly simultaneously 0.22 μm of circulating filtration Miillpore filter；Then, using the ultrafiltration membrance filter of retention relative molecular mass 10000-20000, it is seen that foreign matter and pH value inspection Afterwards, 10ml/ branch encapsulating, 121 DEG C of 15min sterilizing to get.It takes 10 above-mentioned samples to be protected from light and is placed in 25 DEG C of room temperature or so, it is relatively wet It is placed 6 months in the environment of degree 75% ± 5%, solution keeps clear and bright, and the pH value for measuring solution is about 4.4.

The preparation of 6 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1559.1mg of zinc gluconate, 6 hydrate 5.2mg of chromium chloride, 1 hydrate of copper gluconate 1428.5mg (in terms of copper gluconate anhydride), 2 hydrate 324.2mg of manganese gluconate are (with manganese gluconate anhydride Meter), 5 hydrate 133.4mg of sodium selenite, sodium iodide 59.1mg, four water ammonium heptamolybdate 92mg, sorbierite 10g, glycine 50g, L-thiamine 60g, sodium gluconate 5g, 2M gluconic acid solution and 2M sodium gluconate solution is appropriate, appropriate water for injection, add Water for injection is to full dose 10000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by the sorbierite of recipe quantity, glycine, L- tea ammonia The water for injection stirring and dissolving of acid, sodium gluconate proper amount of fresh, it is total with gluconic acid solution and gluconic acid solution solution With adjusting the pH value of solution to 4.3；Zinc gluconate, chromium chloride, copper gluconate, manganese gluconate are used Portugal by step 2 respectively Grape sugar acid solution is acidified fresh water for injection stirring and dissolving；Step 3, by 5 hydrate of sodium selenite, sodium iodide, four water, seven molybdenum The water for injection stirring and dissolving of sour ammonium proper amount of fresh；Step 4 mixes each step solution, then with suitable gluconic acid Solution and sodium gluconate solution adjust pH value to 4.3, and benefit adds to the full amount of water for injection, and stirs evenly simultaneously 0.22 μm of circulating filtration Miillpore filter；Then, with retention relative molecular mass 10000-30000 ultrafiltration membrance filter, through visible foreign matters and pH value inspection Afterwards, by 10ml/ branch encapsulating, 121 DEG C of 15min sterilizings to get.It takes suitable above-mentioned sample to be protected from light and is placed in 30 DEG C, relative humidity It is placed 6 months in the environment of 75% ± 5%, solution keeps clear and bright, and the pH value for measuring solution is 4.3.

The preparation of 7 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1393.7mg of zinc gluconate (in terms of zinc gluconate anhydride), 6 hydrate of chromium chloride 5.2mg, 1 hydrate 1428.5mg of copper gluconate (in terms of copper gluconate anhydride), 2 hydrate of manganese gluconate 324.2mg (in terms of manganese gluconate anhydride), 5 hydrate 133.4mg of sodium selenite, sodium iodide 59.1mg, four water, seven molybdic acid Ammonium 92mg, xylitol 10g, glycine 20g, sodium gluconate 20g, 2M gluconic acid solution and 2M sodium gluconate solution are suitable Amount, appropriate water for injection, add to the full amount of water for injection 20000ml

Preparation process：Supplementary material, step 1, xylitol, glycine, glucose by recipe quantity are weighed or prepared by prescription The water for injection stirring and dissolving of sour sodium proper amount of fresh adjusts the pH value of solution to 4.5 with gluconic acid solution；Step 2, by Portugal Grape saccharic acid zinc hydrate, chromium chloride hydrate, gluconic acid copper hydrate, manganese gluconate hydrate use gluconic acid molten respectively Liquid is acidified fresh water for injection stirring and dissolving；Step 3 uses sodium selenite hydrate, sodium iodide, four water ammonium heptamolybdates in right amount Fresh water for injection stirring and dissolving；Step 4 mixes each step solution, then with suitable gluconic acid solution and grape Saccharic acid sodium solution adjusts pH value to 4.6, and benefit adds to the full amount of water for injection, and stirs evenly simultaneously 0.22 μm of miillpore filter of circulating filtration； Then, then through 0.22 μm of filtering with microporous membrane, after visible foreign matters and pH value check, by 2ml/ branch encapsulating, 121 DEG C of 15min go out Bacterium to get.

The preparation of 8 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1393.7mg of zinc gluconate (in terms of zinc gluconate anhydride), chromium gluconate hydrate (by chromium gluconate weight calculation amount) 12.3mg, 1 hydrate 1428.5mg of copper gluconate (in terms of copper gluconate anhydride), Portugal 2 hydrate 324.2mg of grape saccharic acid manganese (in terms of manganese gluconate anhydride), 5 hydrate 133.4mg of sodium selenite, sodium iodide 59.1mg, four water ammonium heptamolybdate 92mg, sorbierite 20g, taurine 30g, L-ASPARTIC ACID 20g, the poly- second two of VE succinic acid Alcohol ester 10g, 4M gluconic acid solution and 2M sodium gluconate is appropriate, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Supplementary material, step 1, sorbierite, taurine, the L- winter by recipe quantity are weighed or prepared by prescription The water for injection stirring and dissolving of propylhomoserin, VE succinic acid macrogol ester proper amount of fresh is sour by it with gluconic acid solution Change pH value to 4.8；Step 2, by zinc gluconate, chromium gluconate hydrate, gluconic acid copper hydrate, manganese gluconate water It closes object and is acidified fresh water for injection stirring and dissolving with gluconic acid solution respectively；Step 3, by sodium selenite hydrate, iodate The water for injection stirring and dissolving of sodium, four water ammonium heptamolybdate proper amount of fresh；Step 4 mixes each step solution, then with appropriate Gluconic acid solution and sodium gluconate solution adjust pH value to 5.2, benefit adds to the full amount of water for injection, and stirs evenly and recycles 0.22 μm of miillpore filter is filtered, then, then with 0.22 μm of filtering with microporous membrane, 15ml/ branch encapsulating, 121 DEG C of 15min sterilizings, i.e., ?.It takes suitable above-mentioned sample to be protected from light and is placed in 25 DEG C of room temperature or so, placed 6 months in the environment of relative humidity 75% ± 5%, it is molten Liquid keeps clear and bright, and the pH value for measuring solution is 5.2.

The preparation of 9 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1393.7mg of zinc gluconate (in terms of zinc gluconate anhydride), 6 hydrate of chromium chloride 5.2mg, L-ASPARTIC ACID copper hydrate 1033.1mg (with L-aminobutanedioic acid copper weight calculation amount), 2 hydrate 324.2mg of manganese gluconate (in terms of manganese gluconate anhydride), 5 hydrate 133.4mg of sodium selenite, sodium iodide 59.1mg, four water ammonium heptamolybdate 92mg, Sorbierite 20g, taurine 100g, glycine 10g, 3M gluconic acid solution and 2M sodium gluconate solution be appropriate, water for injection In right amount, add to the full amount of water for injection 10000ml

Preparation process：Supplementary material, step 1, taurine, glycine and sorbierite by recipe quantity are weighed or prepared by prescription With the water for injection stirring and dissolving of proper amount of fresh, pH value is acidified to 4.6 with gluconic acid solution；Step 2, by gluconic acid Zinc, chromium chloride, L-aminobutanedioic acid copper, L-aminobutanedioic acid manganese are acidified fresh water for injection stirring and dissolving with gluconic acid solution respectively； Step 3, by 5 hydrate of sodium selenite, sodium iodide, four water ammonium heptamolybdate proper amount of fresh water for injection stirring and dissolving；Step 4, each step solution is mixed, then adjusts pH value to 4.5 with suitable gluconic acid solution and sodium gluconate solution, adds Water for injection stirs evenly simultaneously 0.22 μm of miillpore filter of circulating filtration to full dose；Then, using retention relative molecular mass The ultrafiltration membrance filter of 5000-10000,20ml/ branch encapsulating, 121 DEG C of 15min sterilizing to get.It takes suitable above-mentioned sample to be protected from light to set It in 25 DEG C of room temperature or so, is placed 6 months in the environment of relative humidity 75% ± 5%, solution keeps clear and bright, measures the pH value of solution It is 4.5.

The preparation of 10 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1559mg of zinc gluconate, 6 hydrate 5.2mg of chromium chloride, 1 hydrate of copper gluconate 1428.5mg (in terms of copper gluconate anhydride), 2 hydrate 324.2mg of manganese gluconate are (with manganese gluconate anhydride Meter), 5 hydrate 133.4mg of sodium selenite, sodium iodide 59.1mg, four water ammonium heptamolybdate 92mg, sorbierite 60g, glycine 20g, Gluconic acid 5g, 2M gluconic acid solution and 2M sodium gluconate solution are appropriate, 1M sodium hydroxide solution is appropriate, water for injection is suitable Amount, add to the full amount of water for injection 10000ml

Preparation process：Supplementary material, step 1, sorbierite, glycine, glucose by recipe quantity are weighed or prepared by prescription The water for injection stirring and dissolving of sour proper amount of fresh adjusts the pH value of solution with gluconic acid solution and sodium hydroxide solution solution To 4.5；Zinc gluconate, chromium chloride, copper gluconate, manganese gluconate are acidified newly with gluconic acid solution by step 2 respectively Fresh suitable water for injection stirring and dissolving；Step 3,5 hydrate of sodium selenite, sodium iodide, four water ammonium heptamolybdate proper amount of fresh Water for injection stirring and dissolving；Step 4 mixes each step solution, then with suitable gluconic acid solution, sodium gluconate Solution, sodium hydroxide solution adjust pH value to 4.6, and benefit adds to the full amount of water for injection, and stirs evenly and 0.22 μm of circulating filtration micro- Hole filter membrane 20min；Then, using retention relative molecular mass 5000-10000 ultrafiltration membrance filter, 40ml/ branch encapsulating, 121 DEG C 15min sterilizing to get.

The preparation of 11 various trace elements of embodiment, VII drug combination injection

Prescription：Zinc gluconate hydrate (in terms of zinc gluconate anhydride) 1533.1mg, 6 hydrate of chromium chloride 4.61mg, 1 hydrate 1633.7mg of copper gluconate, 1 hydrate 110.7mg of manganese sulfate, 5 hydrate 146.5mg of sodium selenite, Sodium iodide 53.1mg, four water ammonium heptamolybdate 101.2mg, sorbierite 10g, taurine 180g, sodium gluconate 10g, 1M glucose Acid solution and 2M sodium citrate solution is appropriate, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Supplementary material, step 1, sorbierite, taurine, glucose by recipe quantity are weighed or prepared by prescription The water for injection stirring and dissolving of sour sodium proper amount of fresh adjusts above-mentioned solution ph with gluconic acid solution and sodium citrate solution To 4.1；Step 2 fits zinc gluconate, chromium chloride, copper gluconate, manganese sulfate with gluconic acid solution acidification is fresh respectively The water for injection stirring and dissolving of amount；Step 3, by 5 hydrate of sodium selenite, sodium iodide, four water ammonium heptamolybdate proper amount of fresh Water for injection stirring and dissolving；Step 4 mixes each step solution, then molten with suitable gluconic acid solution and sodium citrate Liquid adjusts pH value to 4.1, and benefit adds to the full amount of water for injection, and stirs evenly simultaneously 0.22 μm of miillpore filter 20min of circulating filtration；So Afterwards, using the ultrafiltration membrance filter of retention relative molecular mass 6000-20000, by 10ml/ branch encapsulating, 121 DEG C of 15min sterilize, i.e., ?.

The preparation of 12 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1403.1mg of zinc gluconate, chromic acetate hydrate 4.41mg (in terms of anhydride), glucose Sour 1 hydrate 1336.7mg of copper, 1 hydrate 135.3mg of manganese sulfate, selenous acid 58.8mg, sodium iodide 65mg, four water ammonium heptamolybdates 82.8mg, sorbierite 2g, glycine 15g, taurine 30g, L-thiamine 8g, L-citrulline 1g, 3M gluconic acid solution and 3M Appropriate sodium gluconate solution, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by the sorbierite of recipe quantity, glycine, taurine, Solution is acidified pH value extremely with gluconic acid solution by the water for injection stirring and dissolving of theanine, L-citrulline proper amount of fresh 4.2；Step 2, the water for injection that chromic acetate, copper gluconate, manganese sulfate are acidified with gluconic acid solution to fresh amount respectively Stirring and dissolving；The water for injection dissolution of step 3, zinc gluconate acidification fresh amount；Step 4, by selenous acid with appropriate new Fresh water for injection stirring and dissolving；Step 4 mixes each step solution, then with suitable gluconic acid solution and glucose Acid sodium solution adjusts pH value to 4.2, and benefit adds to the full amount of water for injection, and stirs evenly simultaneously 0.22 μm of miillpore filter of circulating filtration；So Afterwards, using the ultrafiltration membrance filter of retention relative molecular mass 6000-20000, it is seen that after inspection of foreign substance is qualified, 5ml/ branch encapsulating, 121 DEG C of 15min sterilizing to get.

The preparation of 13 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1520mg of zinc gluconate, 6 hydrate 5.0mg of chromium chloride, cupric sulfate pentahydrate 800mg, grape 2 hydrate 370mg of saccharic acid manganese, 5 hydrate 125mg of sodium selenite, sodium iodide 63mg, four water ammonium heptamolybdate 96mg, sorbierite 10g, taurine 30g, glycine 10g, 3- hydroxy-proline 5g, sodium gluconate 10g, 3M lactic acid solution and 0.5M sodium hydroxide Appropriate solution, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Supplementary material, step 1, sodium iodide, ammonium heptamolybdate, sorb by recipe quantity are weighed or prepared by prescription Alcohol, glycine, taurine, 3- hydroxy-proline proper amount of fresh water for injection stirring and dissolving, with lactic acid solution and hydroxide Solution is adjusted pH value to 4.0 by sodium solution；Chromium chloride, copper sulphate, manganese gluconate are used suitable lactic acid molten by step 2 respectively Liquid is acidified fresh appropriate water for injection stirring and dissolving；Step 3,3 hydrate of zinc gluconate are acidified fresh with lactic acid solution Appropriate water for injection dissolution；Step 4, the water for injection stirring and dissolving by sodium selenite proper amount of fresh；Step 5, by each step Solution mixes, and then with suitable lactic acid solution and sodium hydroxide solution adjusting pH value to 4.1, benefit adds to the full amount of water for injection, Stir evenly simultaneously 0.22 μm of miillpore filter 30min of circulating filtration；Then, using the super of retention relative molecular mass 6000-20000 Membrane filtration, by 2ml/ branch encapsulating, 121 DEG C of 15min sterilizings to get.

The preparation of 14 various trace elements of embodiment, VII drug combination injection

Prescription：2 hydrate 670.3mg of zinc acetate, chromium gluconate 12.26mg (weight is in terms of anhydride), D-Glucose Sour 1 hydrate 1485.2mg of copper, 2 hydrate 350.3mg of maltonic acid manganese, 5 hydrate 133.2mg of sodium selenite, potassium iodide 65.4mg, sodium molybdate (Na2MoO42H2O) 126.1mg, sorbierite 10g, glycine 80g, sodium gluconate 12g, 3M grape Sugar acid solution and 1M sodium hydroxide solution is appropriate, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by the potassium iodide of recipe quantity, sodium molybdate, sorbierite, The water for injection stirring and dissolving of glycine, sodium gluconate proper amount of fresh, gluconic acid solution sodium hydroxide solution is adjusted PH value is about to 4.2；Chromium gluconate, copper gluconate, manganese gluconate are acidified newly with gluconic acid solution by step 2 respectively Fresh water for injection stirring and dissolving；2 hydrate of zinc acetate is acidified fresh appropriate injection with gluconic acid solution by step 3 Water dissolution；Step 4, by the water for injection stirring and dissolving of 5 hydrate proper amount of fresh of sodium selenite；Step 5, by each step solution It mixes, then with suitable gluconic acid solution and sodium hydroxide solution adjusting pH value to 4.3, benefit adds to the full amount of water for injection, Stir evenly simultaneously 0.22 μm of miillpore filter 20min of circulating filtration；By 1ml/ branch encapsulating, 121 DEG C of 15min sterilizings to get.

The preparation of 15 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1590mg of zinc gluconate, chromium gluconate hydrate 13mg (weight is in terms of anhydride), D- 1 hydrate 1500mg of copper gluconate, 2 hydrate 340mg of maltonic acid manganese, 5 hydrate 130mg of sodium selenite, sodium iodide 50mg, sodium molybdate (Na2MoO42H2O) 130mg, sorbierite 20g, taurine 70g, L-citrulline 20g, 3M lactic acid solution and 1M sodium hydroxide solution is appropriate, appropriate water for injection, and add to the full amount of water for injection 10000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by the sodium iodide of recipe quantity, sorbierite, taurine, The water for injection stirring and dissolving of citrulling proper amount of fresh, lactic acid solution and sodium hydroxide solution adjust pH value to 4.0；Step 2, 3 hydrate of zinc gluconate, chromium gluconate, copper gluconate, manganese gluconate is fresh suitable with lactic acid solution acidification respectively The water for injection stirring and dissolving of amount；Step 3, by sodium selenite, the water for injection stirring and dissolving of sodium molybdate proper amount of fresh；Step 4, each step solution is mixed, then adjusts pH value to 4.3 with suitable lactic acid solution and sodium hydroxide solution, adds injection Water stirs evenly simultaneously 0.22 μm of miillpore filter 20min of circulating filtration to full dose；Then, using retention relative molecular mass 5000- 10000 ultrafiltration membrance filter, presses 1ml/ branch, 15ml/ branch encapsulating after inspection, 121 DEG C of 15min sterilizing, packaging, examine to get.

The preparation of 16 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1559mg of maltonic acid zinc, chromium gluconate 12.26mg, 1 hydrate of copper gluconate 1485.2mg, 2 hydrate 350.4mg of manganese gluconate, 5 hydrate 133.2mg of sodium selenite, sodium iodide 53.1mg, four water seven Ammonium molybdate 101.2mg, sorbierite 30g, taurine 100g, 3M gluconic acid solution and 2M citric acid three sodium solution and 1M hydroxide Appropriate sodium solution, appropriate water for injection, add to the full amount of water for injection 10000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by the sodium iodide of recipe quantity, four water ammonium heptamolybdates, 5 hydrate of sodium selenite, sorbierite, taurine proper amount of fresh water for injection stirring and dissolving, by gluconic acid solution and lemon Lemon three sodium solutions of acid adjust pH value to 4.5；Step 2, by 3 hydrate of zinc gluconate, chromium gluconate, manganese gluconate, Portugal The water for injection dissolution that the suitable gluconic acid solution of grape saccharic acid copper is acidified；Step 3 mixes each step solution, then uses Suitable gluconic acid solution and citric acid three sodium solution and sodium hydroxide solution adjust pH value to 5.0, moisturizing constant volume；By solution The membrane filtration for being 50,000 to 100,000 with retention relative molecular mass, then the ultrafiltration with retention relative molecular mass 8000~30000 Film filtering, filtrate examine after press the encapsulating of 10ml/ branch, seal, packaging, examine to get.

The preparation of 17 various trace elements of embodiment, VII drug combination injection

Prescription：3 hydrate 1559mg of zinc gluconate, chromium gluconate hydrate (with chromium gluconate weight calculation amount) 12mg, L-ASPARTIC ACID copper hydrate 1033mg (with L-aminobutanedioic acid copper weight calculation amount), L-aminobutanedioic acid manganese hydrate 232.3mg (with L-aminobutanedioic acid manganese weight calculation amount), 5 hydrate 133mg of sodium selenite, sodium iodide 53mg, four water ammonium heptamolybdate 102mg, sorbierite 20g, glycine 40g, L-arginine 5g, xylitol 5g, sodium gluconate 40g, polyethylene glycol-12-hydroxystearate 5g, 3M Gluconic acid solution and appropriate sodium gluconate solution, appropriate water for injection, add to the full amount of water for injection 5000ml

Preparation process：Weigh or prepare supplementary material by prescription, step 1, by the sodium iodide of recipe quantity, sorbierite, glycine, L-arginine, xylitol, sodium gluconate, the water for injection stirring of polyethylene glycol-12-hydroxystearate proper amount of fresh are molten Gluconic acid solution is acidified pH value to 4.9 by solution；Step 2, by L-aminobutanedioic acid manganese hydrate, the suitable note of L-aminobutanedioic acid copper It penetrates and is dissolved with water；Step 3 dissolves zinc gluconate, the suitable water for injection of chromium gluconate；Step 4, by sodium selenite 5 hydrates, four water ammonium heptamolybdates are dissolved with suitable water for injection；Step 5, by the solution of step 2 successively respectively with step 1 Solution is uniformly mixed；Step 6 mixes the solution of step 3 and the solution of step 5；Step 7, solution and step 6 by step 4 Solution mix well, then adjust pH value to 5.3 with suitable gluconic acid solution and sodium gluconate, moisturizing constant volume；Step 8, by solution with 0.22 μm of filtering with microporous membrane twice, filtrate examine after by 1ml/ branch, 5ml/ branch, 10ml/ branch it is filling, sealing, Packaging to get.

The preparation of 18 various trace elements of embodiment, VII drug combination injection

Prescription：L-ASPARTIC ACID zinc hydrate 1008.1mg (with L-aminobutanedioic acid zinc anhydride weight calculation amount), chromium gluconate (with chromium gluconate weight calculation amount) 12.3mg, 1 hydrate 1485.2mg of copper gluconate, 2 hydrate of manganese gluconate 350.3mg, sodium hydrogen selenite 76.5mg, sodium iodide 53.1mg, 2 hydrate 126.1mg of sodium molybdate, antierythrite 30g, glycine 30g, taurine 90g, sodium gluconate 10g, 2M gluconic acid solution and 1M sodium hydroxide solution is appropriate, appropriate water for injection, Add to the full amount of water for injection 10000ml

Preparation process：Prepare each supplementary material by prescription, step 1, by the glycine of recipe quantity, taurine, antierythrite, Portugal The water for injection stirring and dissolving of grape sodium saccharate proper amount of fresh, adjusts solution for gluconic acid solution and sodium hydroxide solution in right amount PH value is to 4.5；2 hydrate of manganese gluconate, the suitable gluconic acid solution of 2 hydrate of copper gluconate are acidified by step 2 Water for injection (pH=4.5) dissolution；Step 3 dissolves the water for injection of the suitable acidification of L-ASPARTIC ACID zinc hydrate； Step 4 dissolves the water for injection of chromium gluconate fresh amount；Step 5, by the sodium hydrogen selenite of recipe quantity, sodium iodide, 2 hydrate of sodium molybdate is dissolved with suitable water for injection；Step 6 successively fills the solution of step 2 with the solution of step 1 respectively Divide and is uniformly mixed；Step 7 mixes the solution of step 3 and the solution of step 6；Step 8, by the solution of step 4 and step 5 Solution, step 7 solution mix, then with suitable gluconic acid solution and sodium hydroxide solution adjusting pH value to 4.5, moisturizing Constant volume；Step 9, the ultrafiltration membrance filter that solution is used to retention relative molecular mass 10000~30000, then through 0.22 μm of micropore Membrane filtration, filtrate press the encapsulating of 10ml/ branch after examining, sealing, 121 DEG C of 15min sterilizing, packaging, examine to get.

The preparation of 19 various trace elements of embodiment, VII drug combination injection

3 hydrate 909.6mg of prescription Pfansteihl zinc, maltonic acid chromium (with chromium gluconate weight calculation amount) 12.3mg, D- 1 hydrate 1485.2mg of copper gluconate, 2 hydrate 350.3mg of maltonic acid manganese, 5 hydrate 133mg of sodium selenite, iodine Change sodium 53.1mg, four water ammonium heptamolybdate 101.2mg, sorbierite 10g, glycine 30g, sodium gluconate 8g, 2M lactic acid solution and Appropriate sodium gluconate solution, 1M sodium hydroxide solution be appropriate, appropriate water for injection, and add to the full amount of water for injection 10000ml

Preparation process：Prepare supplementary material by prescription, step 1 uses the glycine, sorbierite, sodium gluconate of recipe quantity Lactic acid solution is acidified pH value to 4.3 by the water for injection stirring and dissolving of proper amount of fresh；Step 2, by chromium gluconate, glucose Sour manganese, the copper gluconate acidification of appropriate lactic acid water for injection dissolution, make keep clarify；Step 3 uses zinc lactate in right amount Acidification water for injection dissolution；It is step 4, sodium selenite, sodium iodide, four water ammonium heptamolybdates are water-soluble with suitable injection Solution；Step 5 mixes each step solution, then with suitable lactic acid solution solution, sodium gluconate and sodium hydroxide solution PH value is adjusted to 4.3, moisturizing constant volume；Step 6 uses solution with the ultrafiltration membrane mistake for retaining relative molecular mass 10000~30000 Filter, then through 0.22 μm of filtering with microporous membrane, the encapsulating of 10ml/ branch, sealing are pressed after inspection, 121 DEG C of 15min sterilizings are packed, are examined, To obtain the final product.It respectively takes 10 above-mentioned samples to be protected from light respectively and is placed in 25 DEG C of room temperature or so, place 6 in the environment of relative humidity 75% ± 5% A month, solution kept clear and bright, and the pH value for measuring solution is each about 4.3.

Embodiment 20, pharmaceutical composition intravascular injection irritation test

1, test objective：Observe animal 0.9% physiological saline of intravenous drip, medicine composition injection of the invention and After comparison medicine injection, the vascular stimulation response situation of generation.

2, test material：2.1. animal：The white Female rabbits of the big ear of adult healthy New Zealand, 2.5~3.0kg of weight.

2.2. tested material：Medicine composition injection of the invention and the control of various trace elements medicine composition injection Group, preparation method：Each embodiment of pharmaceutical composition of the invention (embodiment 6, embodiment 9, the preparation of 16 method of embodiment) is taken respectively Injection and VII medicine composition injection control group of various trace elements (the Trace Elements of USP36 Injection injection 4ml) is added in 0.9% physiological saline of 100ml, is mixed.

3, test method：Female rabbits 5, the 1st unused any drug makees the observation of blank parallel control；Other 4 points Not in auris dextra edge intravenous drip contrast solution (according to the various trace elements medicine composition injection pair of the group assignment system of table 1 According to group [multi-microelement injecta (the Trace Elements Injection of USP36)] (referring to the program of 1 method of embodiment Preparation, is then diluted with normal saline) and each embodiment group, then normal saline dilute solution；Administered volume For 20ml/kg, drip velocity is 25~30 drops/min；Left auricular vein is given equal capacity physiological saline and is compared, drip velocity It is identical as test drug.Once a day, continuous drip 5 days.During instillation, the irritation of the observation auricular vein of naked eyes timing daily is anti- It answers.7th day execution rabbit is fixed in bilateral auricular vein proximal part away from drawing materials at injection site 1.0cm~1.5cm with formaldehyde, Conventional organization slice is done, pathological examination is carried out.

4, test result

4.1. naked eyes result：

Intravenous drip the present embodiment each group (respectively by embodiment 6, embodiment 9, the preparation of 16 method of embodiment), the vein of administration Lateral vein slightly to be expanded compared with physiological saline, after being discontinued for 24 hours, it is seen that the oozing of blood at needle thorn forms subcutaneous induration around vein, Side is administered with to intravenous drip physiological saline side no significant difference, other macroscopic results are with physiological saline side without obvious poor It is different.

Various trace elements medicine composition injection control group animal during instillation repeatedly struggles relatively acutely, prompts Control group has certain irritation to body, can cause vascular pain, and that there are the congestions of blood vessel is rubescent, and vascular endothelial cell is slight Swelling, the inflammatory reactions situation such as peripheral tissue edema.

4.2. pathological examination：

Blank control group：See that venous blood lumen is complete under mirror, has no narrow, tube wall has no inflammatory cell infiltration.

Physiological saline side：See that venous blood lumen is complete under (left auricular vein, instillation normal saline solution) mirror, tube wall is shown in A little inflammatory cell infiltration.It is remaining to have no obvious lesion.

Test medicine group of the present invention：Venous blood lumen is seen under (right auricular vein, instil pharmaceutical composition of the invention) mirror Completely, tube wall is shown in a little inflammatory cell infiltration.It is remaining to have no obvious lesion.

Venous blood lumen swelling is seen under control drug group (right auricular vein, instillation control drug group solution) mirror, tube wall is scorching Property cellular infiltration is obvious.

5, conclusion (of pressure testing)

After rabbit auricular vein instils dilute solution 5 days of pharmaceutical composition of the invention of the invention, injection site without Finding of naked eye irritative response, and plant irritative response of the control group there are finding of naked eye of microelement composition.Micro- disease Reason inspection result shows to have no blood vessel structure exception, endothelial injuries, thrombosis and other pathological changes, this result and solvent Control group is consistent；Then there is damage pathologically in control drug group.Prompt：Pharmaceutical composition of the invention is to blood vessel without obvious thorn Swash property, and the control group of various trace elements composition then has obvious irritation to blood vessel.

Industrial applicibility etc. and its illustrate：

It is described the invention in detail above by specific embodiment and embodiment, it will nevertheless be understood that these are said Bright it is not intended to limit the scope of the present invention in any way, and related technical personnel obviously can be without departing from spirit of the invention and guarantor In the case where protecting range, technical solutions and their implementation methods of the present invention can be carried out with a variety of modifications, improvement and replacement and group It closes, to realize the technology of the present invention, these are because falling within the scope of protection of the present invention.In particular, it should be pointed out that, it will be understood that Much the variation of details is possible, and all similar replacements and change are apparent for a person skilled in the art , they are considered as including in spirit of the invention, range and content, and the present invention is not limited to above-described embodiments.

Claims

1. the pharmaceutical composition of various trace elements VII, it is characterised in that：One unit dose or unit formulation or unit volume The composition in main ingredient component weight number or the ratio between parts by weight be：Containing 18~22 μ g of zinc (Zn), 18~22 μ g of copper (Cu), 3.6~4.4 μ g of manganese (Mn), 0.9~0.11 μ g of chromium (Cr), 3.6~4.4 μ g of selenium, 4.5~5.5 μ g of iodine, 4.5~5.5 μ g of molybdenum；Or Person contains the weight of above-mentioned each main ingredient component in the composition of said one unit dose or unit formulation or unit volume It is 0.25~50 times several or parts by weight；

Wherein, zinc or zinc salt are selected from zinc gluconate, lactobionic acid zinc, zinc citrate, zinc lactate or Pfansteihl zinc, zinc acetate, door Aspartic acid zinc, glycine zine, zinc glutamate or their hydrate or their isomers or zinc ion are pharmaceutically acceptable One of salt is a variety of；

Copper or mantoquita be selected from copper sulphate, copper gluconate, lactobionic acid copper, copper citrate, copper lactate or Pfansteihl copper, copper acetate, D- or L- or DL- L-aminobutanedioic acid copper, cupric glycinate, cupric glutamate or their isomers or their hydrate or cupric from One of sub- pharmaceutically acceptable salt is a variety of；

Manganese or manganese salt be selected from manganese sulfate, manganese gluconate, lactobionic acid manganese, manganese citrate, manganese lactate or Pfansteihl manganese, manganese acetate, L-ASPARTIC ACID manganese, DL- L-aminobutanedioic acid manganese, Mn-Gly, glutamic acid manganese or their isomers or their hydrate or two One of valence manganese ion pharmaceutically acceptable salt is a variety of；

Chromium or chromic salts are selected from chromium chloride, chromium sulfate, chromium gluconate, chromium citrate, Chromic lactate, L-aminobutanedioic acid chromium, chromic acetate, sweet Propylhomoserin chromium, glutamic acid chromium or their isomers or one of their hydrates or trivalent chromic ion pharmaceutically acceptable salt Or it is a variety of；

Iodine in potassium iodide or sodium iodide or iodine one of pharmaceutically acceptable salt or a variety of；

Molybdenum selected from but not limited to sodium molybdate or its molybdic acid sodium hydrate, ammonium molybdate or ammonium molybdate hydrate or molybdic acid or molybdic acid medicine One of acceptable salt or a variety of on.

2. the pharmaceutical composition of various trace elements VII, it is characterised in that：One unit dose or unit formulation or unit volume The composition in main ingredient component weight number or the ratio between parts by weight be：Containing 18~22 μ g of zinc (Zn), 18~22 μ g of copper (Cu), 3.6~4.4 μ g of manganese (Mn), 0.9~0.11 μ g of chromium (Cr), 3.6~4.4 μ g of selenium, 4.5~5.5 μ g of iodine, 4.5~5.5 μ g of molybdenum；Or Person contains the weight of above-mentioned each main ingredient component in the composition of said one unit dose or unit formulation or unit volume It is 0.25~50 times several or parts by weight；The composition can form injection with pharmaceutically acceptable auxiliary material；

Wherein, zinc or zinc salt are selected from zinc gluconate, lactobionic acid zinc, zinc citrate, zinc lactate or Pfansteihl zinc, zinc acetate, door Aspartic acid zinc, glycine zine, zinc glutamate or their isomers or their hydrate or zinc ion are pharmaceutically acceptable One of salt is a variety of；

Chromium or chromic salts are selected from chromium chloride, chromium sulfate, chromium gluconate, chromium citrate, Chromic lactate, L-aminobutanedioic acid chromium, chromic acetate, sweet Propylhomoserin chromium, glutamic acid chromium or their isomers or one of their hydrates or trivalent chromic ion pharmaceutically acceptable salt Or it is a variety of；Selenium is selected from the one or more of selenous acid, sodium selenite or its hydrate or the acceptable pharmaceutical salts of selenous acid；

Iodine is selected from one or more of potassium iodide or sodium iodide；

Molybdenum is selected from sodium molybdate or the pharmaceutically acceptable salt of its molybdic acid sodium hydrate, ammonium molybdate or ammonium molybdate hydrate or molybdic acid One of or it is a variety of；

Pharmaceutically acceptable auxiliary material or excipient are in addition to water for injection, it may include pharmaceutically acceptable amides compound, Pharmaceutically acceptable aminated compounds, amino acid or its pharmaceutical salts, for example：D- or L- or DL-lysine or Lysine Acetate or Arginine or acetic arginine or taurine or glycine or L-aminobutanedioic acid or Monosodium L-aspartate or D- or L- or DL-histidine Or cysteine or methionine or its salt, pharmaceutically acceptable organic acid or its salt, pharmaceutically acceptable alcohol compound or Their pharmaceutically acceptable salt etc. or their isomers or one of its solvated compounds or its hydrate or a variety of.

3. the pharmaceutical composition of various trace elements VII, it is characterised in that：One unit dose or unit formulation or unit volume The composition in main ingredient component weight number or the ratio between parts by weight be：Containing 18~22 μ g of zinc (Zn), 18~22 μ g of copper (Cu), 3.6~4.4 μ g of manganese (Mn), 0.9~0.11 μ g of chromium (Cr), 3.6~4.4 μ g of selenium, 4.5~5.5 μ g of iodine, 4.5~5.5 μ g of molybdenum；Or Person contains the weight of above-mentioned each main ingredient component in the composition of said one unit dose or unit formulation or unit volume It is 0.25~50 times several or parts by weight；The composition can form injection with pharmaceutically acceptable auxiliary material；

Wherein, zinc or zinc salt are selected from zinc gluconate or zinc gluconate hydrate, zinc gluconate (II) dihydrate, grape 3 hydrate of saccharic acid zinc, lactobionic acid zinc or lactobionic acid zinc hydrate, zinc citrate or three zinc of citric acid or its zinc citrate hydrate Zinc citrate dihydrate, zinc lactate, 3 hydrate of Pfansteihl zinc, Pfansteihl zinc, 3 hydrate of Pfansteihl zinc, zinc acetate, acetic acid One or more of 2 hydrate of zinc, D- or L- or DL- L-aminobutanedioic acid zinc, glycine zine, zinc glutamate or its hydrate；

Copper or mantoquita are selected from copper sulphate, copper sulfate monohydrate, three brochanites, cupric sulfate pentahydrate, copper gluconate, copper gluconate 1 hydrate, 2 hydrate of copper gluconate, lactobionic acid copper or lactobionic acid copper hydrate, copper citrate or three bronze medal of citric acid or its lemon 2.5 hydrate of lemon acid copper, copper lactate or Pfansteihl copper or its hydrate, D- or L- or DL- L-aminobutanedioic acid copper or their hydration One or more of object, copper acetate or its 1 hydrate of copper acetate, cupric glycinate, cupric glutamate；

Manganese or manganese salt be selected from 1 hydrate of manganese sulfate or manganese sulfate, manganese gluconate, manganese gluconate hydrate, lactobionic acid manganese, Or lactobionic acid manganese hydrate, manganese citrate or three manganese of citric acid or manganese citrate hydrate, manganese lactate or Pfansteihl manganese or its water Close object, 4 hydrate of manganese acetate or manganese acetate, L-ASPARTIC ACID manganese, DL- L-aminobutanedioic acid manganese, Mn-Gly, glutamic acid manganese or its water Close one or more of object；

Chromium or chromic salts are selected from chromium chloride, 6 hydrate of chromium chloride, chromium sulfate, 6 hydrate of chromium sulfate, chromium gluconate or glucose Sour chromium hydrate, chromium citrate or chromium citrate hydrate, Chromic lactate or Pfansteihl chromium or its hydrate, D- or L- or DL- Aspartic acid chromium or D- or 3 hydrate of L- or DL-- L-aminobutanedioic acid chromium, chromic acetate, glycine chromium, glutamic acid chromium or its hydrate It is one or more；Selenium is selected from selenous acid, sodium selenite or its hydrate, 5 hydrate of sodium selenite or the acceptable medicine of selenous acid It is one or more with salt；

Iodine is selected from one or more of potassium iodide or sodium iodide；Molybdenum is selected from sodium molybdate, 2 hydrate of sodium molybdate, ammonium molybdate, molybdic acid One or more of 4 hydrate of ammonium, 4 hydrate of ammonium heptamolybdate；

Pharmacy in above-mentioned composition and pharmaceutically acceptable auxiliary material or excipient composition injection, in addition to water for injection Upper one of acceptable auxiliary material or excipient or a variety of contents in the injection of a unit dose are selected from 0.0010 ~0.40g is more preferably 0.010~0.30g, more preferably 0.020~0.20g；

Pharmaceutically acceptable auxiliary material or excipient are in addition to water for injection, it may include pharmaceutically acceptable amides compound, Pharmaceutically acceptable aminated compounds, amino acid or its pharmaceutical salts, for example：D- or L- or DL-lysine or Lysine Acetate or Arginine or acetic arginine or taurine or glycine or L-aminobutanedioic acid or Monosodium L-aspartate or D- or L- or DL-histidine Or cysteine or methionine or its salt, pharmaceutically acceptable organic acid or its salt, pharmaceutically acceptable alcohol compound or Their pharmaceutically acceptable salt etc. or their chiral isomer or one of its solvated compounds or its hydrate or It is a variety of.

4. the pharmaceutical composition of various trace elements VII, it is characterised in that：One unit dose or unit formulation or unit volume The composition in main ingredient component weight number or the ratio between parts by weight be：Containing 20 μ g of zinc (Zn), 20 μ g of copper (Cu), manganese (Mn) 4.0 μ g, 0.10 μ g of chromium (Cr), 4.0 μ g of selenium, 5.0 μ g of iodine, 5.0 μ g of molybdenum；Or in said one unit dose or unit formulation or 0.25~50 times of weight number or parts by weight in the composition of unit volume containing above-mentioned each main ingredient component；The composition Injection can be formed with pharmaceutically acceptable auxiliary material；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit volume The ratio between the weight number of main ingredient component or parts by weight are about in the composition：Containing 40 μ g of zinc (Zn), 40 μ g of copper (Cu), manganese (Mn) 8.0 μ g, 0.20 μ g of chromium (Cr), 8.0 μ g of selenium, 10.0 μ g of iodine, 10.0 μ g of molybdenum；The composition can be with pharmaceutically acceptable auxiliary material group At injection；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit volume The ratio between the weight number of main ingredient component or parts by weight are about in the composition：Containing 60 μ g of zinc (Zn), 60 μ g of copper (Cu), manganese (Mn) 12.0 μ g, 0.30 μ g of chromium (Cr), 12.0 μ g of selenium, 15.0 μ g of iodine, 15.0 μ g of molybdenum；The composition can be with pharmaceutically acceptable auxiliary material Form injection；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit volume The ratio between the weight number of main ingredient component or parts by weight are about in the composition：Containing 100 μ g of zinc (Zn), 100 μ g of copper (Cu), manganese (Mn) 20.0 μ g, 0.50 μ g of chromium (Cr), 20.0 μ g of selenium, 25.0 μ g of iodine, 25.0 μ g of molybdenum；The composition can be with pharmaceutically acceptable auxiliary material Form injection；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit volume The ratio between the weight number of main ingredient component or parts by weight are about in the composition：Containing 200 μ g of zinc (Zn), 200 μ g of copper (Cu), manganese (Mn) 40.0 μ g, 1.0 μ g of chromium (Cr), 40.0 μ g of selenium, 50.0 μ g of iodine, 50.0 μ g of molybdenum；The composition can be with pharmaceutically acceptable auxiliary material Form injection；

The pharmaceutical composition of various trace elements of the invention more preferably, a unit dose or unit formulation or unit volume The ratio between the weight number of main ingredient component or parts by weight are about in the composition：Containing 400 μ g of zinc (Zn), 400 μ g of copper (Cu), manganese (Mn) 80.0 μ g, 2.0 μ g of chromium (Cr), 80.0 μ g of selenium, 100.0 μ g of iodine, 100.0 μ g of molybdenum；The composition can with it is pharmaceutically acceptable auxiliary Material composition injection；

Manganese is selected from 1 hydrate of manganese sulfate or manganese sulfate, manganese gluconate, manganese gluconate hydrate, lactobionic acid manganese or lactose Sour manganese hydrate, manganese citrate or three manganese of citric acid or manganese citrate hydrate, manganese lactate or Pfansteihl manganese or its hydrate, vinegar In 4 hydrate of sour manganese or manganese acetate, L-ASPARTIC ACID manganese, DL- L-aminobutanedioic acid manganese, Mn-Gly, glutamic acid manganese or its hydrate One or more；

Chromium or chromic salts are selected from chromium chloride, 6 hydrate of chromium chloride, chromium sulfate, 6 hydrate of chromium sulfate, chromium gluconate or glucose Sour chromium hydrate, chromium citrate or chromium citrate hydrate, Chromic lactate or Pfansteihl chromium or its hydrate, D- or L- or DL- Aspartic acid chromium or D- or 3 hydrate of L- or DL-- L-aminobutanedioic acid chromium, chromic acetate, glycine chromium, glutamic acid chromium or its hydrate It is one or more；Selenium is selected from selenous acid, sodium selenite, 5 hydrate of sodium selenite, sodium hydrogen selenite or the acceptable medicine of selenous acid With one or more of salt；Iodine is selected from one or more of potassium iodide or sodium iodide；Molybdenum is selected from sodium molybdate, 2 water of sodium molybdate Close one or more of object, ammonium molybdate, 4 hydrate of ammonium molybdate, 4 hydrate of ammonium heptamolybdate；

Pharmaceutically acceptable auxiliary material or excipient are in addition to water more preferably：Lysine, the Lysine Acetate, half of D- or L- or DL- Cystine, methionine, arginine, acetic arginine, L-aminobutanedioic acid, Monosodium L-aspartate, glutamic acid, glycine, taurine, figured silk fabrics ammonia Acid, threonine, cysteine, cystine, glutamine, 5- oxylysine, histidine, 3- hydroxy-proline, 4- hydroxyl dried meat ammonia Acid, proline, ornithine, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4-Aminobutanoicacid, 2- amino -2- Methylpropanoic acid, 2- methyl -3- alanine, 2,6- diaminopimelic acid, 2- amino-3-phenyl butyric, 4- hydroxyarginine, 4- It is hydroxyl ornithine, 4- hydroxyhomoarginine, 2,4-diamino-butanoic, malic acid, succinic acid, ascorbic acid, L-AA, different Ascorbic acid, sodium isoascorbate, niacin, niacinamide, pantothenic acid, sodium pantothenate, citric acid, sodium citrate, lactic acid, sodium lactate, cream Saccharic acid, sodium lactonic, gluconic acid, sodium gluconate, trehalose, urea, thiocarbamide, maltitol, sorbierite, mannitol, cream In sugar alcohol, xylitol, antierythrite or its hydrate or their pharmaceutically acceptable salt or their chiral isomer etc. It is one or more.

5. VII pharmaceutical composition of various trace elements according to claim 1 to 3, it is characterised in that：Of the invention is a variety of micro- Main ingredient group in the composition of the medicine composition injection of secondary element V, a unit dose or unit formulation or unit volume The ratio between the weight number divided or parts by weight are：

3 hydrate of zinc gluconate or zinc gluconate hydrate, 2 hydrate of zinc gluconate or zinc gluconate 125.4357-153.3103 μ g (with zinc gluconate anhydride weight calculation amount) or 2 hydrate 60.3257- of zinc acetate or zinc acetate 73.7315 μ g (with 2 hydrated basis weight of zinc acetate) or L- or D- or DL- L-aminobutanedioic acid zinc or L- or D- or DL- L-aminobutanedioic acid Zinc hydrate 90.724-110.8849 μ g (with L-aminobutanedioic acid zinc anhydride weight calculation amount),

Copper gluconate or 2 hydrate 128.5666-157.1369 μ g of 1 hydrate of copper gluconate or copper gluconate are (with Portugal Grape saccharic acid copper anhydride weight calculation amount) or copper sulphate or cupric sulfate pentahydrate 70.7309-86.4489 μ g (counted weight with cupric sulfate pentahydrate Amount) or D- or L- or DL- L-aminobutanedioic acid copper or D- or L- or DL- L-aminobutanedioic acid copper hydrate 92.9745-113.6355 μ g (with L-aminobutanedioic acid copper anhydride weight calculation amount) or 1 hydrate 56.5581-69.1265 μ g of copper acetate,

Manganese chloride or 4 hydrate 8.2458-10.0782 μ g (with manganese chloride weight calculation amount) of 2 hydrate of manganese chloride or manganese chloride or Portugal Grape saccharic acid manganese or 2 hydrate 29.1748-35.6581 μ g of manganese gluconate (with manganese gluconate anhydride weight calculation amount) or sulfuric acid 1 hydrate 11.07455-13.5356 μ g or D- of manganese or the hydration of L- or DL- L-aminobutanedioic acid manganese or D- or L- or DL- L-aminobutanedioic acid manganese Object 20.9113-25.5583 μ g (with L-aminobutanedioic acid anhydrous manganese object weight calculation amount),

6 hydrate 0.4612-0.5637 μ g of chromium chloride or chromium gluconate or chromium gluconate hydrate (with chromium gluconate without Water object weight calculation amount) 1.1034-1.3486 μ g or D- or 3 hydrate 0.43558-0.53238 μ g of L- or DL- L-aminobutanedioic acid chromium or lemon Lemon acid chromium 1.0719-1.3102 μ g；

Selenium is selected from 5 hydrate of selenous acid 5.8792-7.1858 μ g or sodium selenite 7.9097--9.6675 μ g or sodium selenite 11.9897-14.654 μ g or sodium hydrogen selenite 6.8817-8.411 μ g or its hydrate or the acceptable pharmaceutical salts of selenous acid It is one or more；

Iodine is selected from potassium iodide 5.8865-7.1946 μ g or sodium iodide 5.3152-6.4964 μ g；Molybdenum is selected from sodium molybdate or sodium molybdate 2 Hydrate 11.3485-13.8704 μ g (with 2 hydrated basis weight of sodium molybdate) or four water ammonium heptamolybdate 8.2810-10.1213 μ g；

Or contain above-mentioned each main ingredient component in the composition of said one unit dose or unit formulation or unit volume Weight number or 0.25~50 times of parts by weight；The composition can be injected with pharmaceutically acceptable auxiliary material or excipient composition Agent；In the injection of aforementioned pharmaceutical compositions, in the pharmaceutically acceptable auxiliary material or excipient in addition to water for injection One or more contents in the injection of a unit dose are selected from 0.0010~0.40g, more preferably for 0.010~ 0.30g, more preferably 0.020~0.20g；

6. VII pharmaceutical composition of various trace elements described in -5 according to claim 1, it is characterised in that：One unit dose or The ratio between the weight number of main ingredient component or parts by weight are in the composition of unit formulation or unit volume：

3 hydrate of zinc gluconate or zinc gluconate hydrate, 2 hydrate of zinc gluconate or zinc gluconate 139.372993 μ g or 139.37299 μ g or 139.373 μ g or 139.37 μ g or 139.4 μ g or 139 μ g or 140 μ g are (with grape Saccharic acid zinc anhydride weight calculation amount) or D- or L- or DL- L-aminobutanedioic acid zinc or D- or L- or DL- L-aminobutanedioic acid zinc hydrate 100.8044 μ g or 100.804 μ g or 100.8 μ g or 101 μ g or (with L-aminobutanedioic acid zinc weight calculation amount)；

6 hydrate of chromium chloride 0.51244326 μ g or 0.5124433 μ g or 0.51244 μ g or 0.5125 μ g or 0.513 μ g or 0.514 μ g or 0.52 μ g or chromium gluconate or chromium gluconate hydrate 1.225959689 μ g or 1.22596 μ g or 1.226 μ G or 1.227 μ g or 1.23 μ g (with chromium gluconate weight calculation amount)；Copper gluconate or 1 hydrate of copper gluconate or glucose Sour 2 hydrate of copper, 142.8517469 μ g or 142.8517 μ g or 142.852 μ g or 142.85 μ g or 142.9 μ g or 143 μ g (with Copper gluconate weight calculation amount) or cupric sulfate pentahydrate 78.589865 μ g or 78.59 μ g or 78.6 μ g or 79 μ g；Manganese gluconate or 2 hydrate of manganese gluconate 32.416454 μ g or 32.4165 μ g or 32.416 μ g or 32.417 μ g or 32.42 μ g or 32.4 μ g Or 32.5 μ g or 32 μ g or 33 μ g (with manganese gluconate weight calculation amount) or 1 hydrate of manganese sulfate 12.30506 μ g or 12.305 μ g or 12.31 μ g or 12.3 μ g or manganese chloride 9.161995 μ g or 9.162 μ g or 9.16 μ g or 9.2 μ g or D- or L- or DL- winter ammonia Sour manganese or D- or L- or DL- L-aminobutanedioic acid manganese hydrate 23.2348 μ g or 23.235 μ g or 23.24 μ g or 23.23 μ g or 23.2 μ G or 23.3 μ g ((with L-aminobutanedioic acid anhydrous manganese object weight calculation amount)；

Selenous acid 6.532516 μ g or 6.53252 μ g or 6.5325 μ g or 6.533 μ g or 6.53 μ g or 6.54 μ g or 6.5 μ g or 6.6 μ g or sodium selenite or 5 hydrate of sodium selenite 13.321835 μ g or 13.32184 μ g or 13.3218 μ g or 13.322 μ g Or 13.32 μ g or 13.34 μ g or 13.3 μ g or 13.4 μ g (with 5 hydrated basis weight of sodium selenate) or sodium hydrogen selenite 7.646342 μ g or 7.646 μ g or 7.65 μ g or 7.7 μ g；Sodium iodide 5.90583136 μ g or 5.9058314 μ g or 5.90583 μ g or 5.9058 μ g or 5.906 μ g or 5.91 μ g or 5.9 μ g or 6.0 μ g or potassium iodide 6.540583 μ g or 6.54058 μ g or 6.5406 μ g or 6.541 μ g or 6.54 μ g；Four water ammonium heptamolybdates 9.201138 μ g or 9.20114 μ g or 9.2012 μ g or 9.2011 μ g or 9.201 μ G or 9.2 μ g or 2 hydrate of sodium molybdate 12.60944 μ g or 12.6094 μ g or 12.609 μ g or 12.61 μ g or 12.6 μ g；Or In the composition of said one unit dose or unit formulation or unit volume containing above-mentioned each main ingredient component weight number or 0.25~50 times of parts by weight；The composition can be prepared into injection with pharmaceutically acceptable auxiliary material or excipient；Upper It states in the injection of pharmaceutical composition, one of pharmaceutically acceptable auxiliary material or excipient in addition to water for injection or more Content of the kind in the injection of a unit dose is selected from 0.0010~0.40g, is more preferably 0.010~0.30g, more preferably For 0.020~0.20g；

Pharmaceutically acceptable auxiliary material or excipient are in addition to water more preferably：Lysine, the Lysine Acetate, half of D- or L- or DL- Cystine, methionine, arginine, acetic arginine, L-aminobutanedioic acid, Monosodium L-aspartate, glutamic acid, glycine, taurine, figured silk fabrics ammonia Acid, threonine, cysteine, cystine, glutamine, 5- oxylysine, histidine, 3- hydroxy-proline, 4- hydroxyl dried meat ammonia Acid, proline, ornithine, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4-Aminobutanoicacid, 2- amino -2- Methylpropanoic acid, 2- methyl -3- alanine, 2,6- diaminopimelic acid, 2- amino-3-phenyl butyric, 4- hydroxyarginine, 4- It is hydroxyl ornithine, 4- hydroxyhomoarginine, 2,4-diamino-butanoic, malic acid, succinic acid, ascorbic acid, L-AA, different Ascorbic acid, sodium isoascorbate, niacin, niacinamide, pantothenic acid, sodium pantothenate, citric acid, sodium citrate, lactic acid, sodium lactate, cream Saccharic acid, sodium lactonic, gluconic acid, sodium gluconate, trehalose, urea, thiocarbamide, maltitol, sorbierite, mannitol, cream One of sugar alcohol, xylitol, antierythrite or its hydrate or their pharmaceutically acceptable salt or their isomers etc. Or it is a variety of.

7. VII pharmaceutical composition of various trace elements described in -6 according to claim 1, it is characterised in that：Of the invention is a variety of micro- Main ingredient group in the composition of the medicine composition injection of secondary element VII, a unit dose or unit formulation or unit volume The ratio between the weight number divided or parts by weight are：2 hydrate of zinc acetate 67.0286 μ g or 67.029 μ g or 67.03 μ g or 67.1 μ g Or 67.0 μ g, chromium gluconate or 1.226 μ g or 1.227 μ g or 1.23 μ g or 6 hydrate of chromium chloride 0.5125 μ g or 0.513 μ g Or 0.514 μ g or 0.52 μ g or D- or 3 hydrate of L-ASPARTIC ACID chromium or 3 hydrate of L-aminobutanedioic acid chromium, 0.4839 μ g or 0.484 μ G or 0.49 μ g, 2 hydrate of copper gluconate or 1 hydrate of copper gluconate or copper gluconate 142.852 μ g or 142.85 μ g Or 142.9 μ g or 143 μ g (with copper gluconate weight calculation amount) or 78.59 μ g of cupric sulfate pentahydrate or 78.6 μ g or 79 μ g, manganese sulfate 1 Hydrate 12.305 μ g or 12.31 μ g or 12.3 μ g or 2 hydrate of manganese gluconate 32.416 μ g or 32.417 μ g or 32.42 μ g Or 32.4 μ g or 32.5 μ g or 32 μ g or 33 μ g (with manganese gluconate weight calculation amount)；Selenous acid 6.5325 μ g or 6.533 μ g or 6.53 μ g or 6.54 μ g or 6.5 μ g or 6.6 μ g or sodium selenite or 5 hydrate of sodium selenite 13.322 μ g or 13.32 μ g or 13.34 μ g or 13.3 μ g or 13.4 μ g (with 5 hydrated basis weight of sodium selenate) or sodium hydrogen selenite 7.646 μ g or 7.65 μ g or 7.7μg；Sodium iodide 5.9058 μ g or 5.906 μ g or 5.91 μ g or 5.9 μ g or 6.0 μ g；Four water ammonium heptamolybdates, 9.2012 μ g or 9.2011 μ g or 9.201 μ g or 9.2 μ g；Or in said one unit dose or unit formulation or the composition of unit volume In the weight number containing above-mentioned each main ingredient component or 0.25~50 times of parts by weight；The composition can with it is pharmaceutically acceptable Auxiliary material or excipient form injection；In the injection of aforementioned pharmaceutical compositions, can pharmaceutically connect in addition to water for injection One of auxiliary material or excipient for receiving or a variety of contents in the injection of a unit dose be selected from 0.0010~ 0.40g is more preferably 0.010~0.30g, more preferably 0.020~0.20g.

8. the pharmaceutical composition of various trace elements VII described in -7 according to claim 1, it is characterised in that：Preparation method choosing From：The pharmaceutical salts of zinc, the pharmaceutical salts of manganese, the pharmaceutical salts of copper, the pharmaceutical salts of chromium are used suitable injection by method one, step 1 one by one It is dissolved with water or is dissolved with the water for injection of suitable acidification；Step 2, by selenous acid or its pharmaceutical salts, the pharmaceutical salts of molybdenum, iodine Pharmaceutical salts are dissolved with suitable water for injection；Each step solution is uniformly mixed by step 3, then with pharmaceutically acceptable pH Regulator adjusts pH value between 3.8~5.2, and more preferably pH value is between 4.0~4.8 or ultrafiltration membrane removes heat source, or adds and live Property carbon decoloring, filter decarburization, then moisturizing constant volume, refined filtration is examined, filling, is sealed, is sterilized, pack, examines.Wherein, acidification The upper acceptable pH adjusting agent of injection water system medication is acidified, and pH is usually between 3.5-5.0.

Or method two, step 1, the pharmaceutical salts of molybdenum or other auxiliary materials or the suitable water for injection of excipient dissolved；Step 2, By manganese ion pharmaceutically acceptable salt, copper ion pharmaceutically acceptable salt respectively with suitable water for injection dissolve or with fit The water for injection of the acidification of amount dissolves；It is step 3, the acceptable pharmaceutical salts of zinc ion are water-soluble with the injection of suitable acidification Solution；Step 4 dissolves chromium ion pharmaceutically acceptable salt with suitable water for injection or with the water for injection of suitable acidification Dissolution；Step 5 dissolves selenous acid or its pharmaceutical salts, the pharmaceutical salts of iodine with suitable water for injection respectively；Step 6, by step 2 solution is uniformly mixed with the solution of step 3 respectively；Step 7 mixes the solution of step 1 and the solution of step 4；Step 8, The solution of step 6 and the solution of step 7 are mixed, then existed with the pH value that pharmaceutically acceptable pH adjusting agent adjusts solution Between 3.8~5.2, preferable ph is between 4.0~4.8；Step 9 adds proper amount of active carbon to decolourize in solution, filters decarburization, or Filtering with microporous membrane, or retention relative molecular mass is used to mix for 0.3 ten thousand to 300,000 membrane filtration or above-mentioned filter method It uses, it is preferred to use the ultrafiltration membrane of retention relative molecular mass 3000~60000 removes remaining heat source, moisturizing constant volume；0.20- 0.45 μm of miillpore filter or ultrafiltration etc. carry out refined filtration, examine, filling, seal, and sterilize, and pack, and examine.Wherein, the injection of acidification It is acidified with water system with pharmaceutically acceptable pH adjusting agent, pH is usually between 3.5-5.0；

Different modes can be used in step in above-mentioned each method, in the case where not violating pharmaceutical principle, intersection or interaction replacement make With.

9. the pharmaceutical composition of various trace elements VII according to claims 1 to 7, it is characterised in that：Its purposes is： Application in the drug of preparation prevention or treatment people and mammal zinc, manganese, copper, selenium, chromium, iodine, molybdenum shortage or its syndrome.