CN1562002A - Novel anti-biological cell free redical oxidation injury mixture - Google Patents
Novel anti-biological cell free redical oxidation injury mixture Download PDFInfo
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Abstract
A mixture for preventing and treating the free radical oxidizing damage of biologic cells, such as presenile dementia, Parkinson's disease, cerebrosclerosis, apoplexy, cardiovascular disease, tumor, etc is prepared from VC, VE and melatonin.
Description
Technical field:
The present invention is a kind of novel anti biological cell free-radical oxidation damage mixture in the biological technical field.
Background technology:
Along with the progress of modern medicine science and technology, it has been recognized that the free-radical oxidation damage of cell and the relation between the health.More and more evidences shows, many diseases all be since the oxidation of body and antioxidative unbalance due to.When the anti-oxidation function of body was low, excessive free radical was understood attack cells, caused the oxidative damage of cell; When the oxidative damage of cell reached certain degree, human body will produce various diseases.The flexibility decrease that at present verified pathological change relevant with the free-radical oxidation damage and disease comprise aging, nervous system degeneration (presenile dementia, parkinson sexually transmitted disease (STD), sclerencephaly), apoplexy, cardiovascular disease (angina pectoris, myocardial ischemia, coronary atherosclerosis), tumor, cataract and skin, wrinkle of skin or the like.In addition, in some treatment of diseases process, also can produce a large amount of free radicals.The necessary partial supply of blood flow of temporary interruption when performing the operation as heart, or when the treatment of thrombus dissolving, reopen supply of blood flow, and for example when human organ transplant, donor organ also can cause the anoxia and the ischemia of cell in by storage and transportation, these therapeutic processes tend to cause ischemia and perfusion again, cause ischemia and reperfusion injury, influence therapeutic effect, the basis of the main pathology of ischemia and reperfusion injury is exactly the free-radical oxidation damage of organ.For another example in the radiotherapy and chemotherapy process of tumor, also can produce a large amount of free radicals, cause body oxidative damage widely, cause other side effect, therefore, these oxidative damages reduce greatly and have limited operation, radiotherapy, the clinical effectiveness of chemotherapy, even increased the weight of patient's symptom sometimes, at the damage of cell free-radical oxidation, and the hazardness in the disease generating process, antioxidant has been widely used in clinical, and the side effect that in prevention and the above-mentioned lysis of treatment, occurs, obtained certain effect.
The antioxidant of the damage of antibiont cellular oxidation at present reaches tens of kinds, and the most frequently used, comprises vitamin C, vitamin E, ubiquinone, melatonin, glutathione of small-molecular weight or the like, and macromolecular antioxidant has superoxide dismutase, peroxidase etc.The effect of most of antioxidant all has similarity, and these antioxidants can both provide in the electronics and harmful free radicals.But, since the difference of molecular structure, the distribution difference of different antioxidants in cell, and therefore, just there is very big difference in their antioxidation.Classical antioxidant has vitamin C, ascorbic English spelling (Ascorbic acid or Vitamin C), in many animals and plants food the different content vitamin C is arranged all, vitamin C is at first synthetic by Englishize scholar Walter Haworth in 1933, be used as the antioxidant extensive use, belong to water-soluble substances, in body, mainly be distributed in cytoplasm, seldom be present in cell membrane, so the antioxidation of cell membrane is limited.Another kind of classical antioxidant vitamin E; the English spelling of vitamin E is (α-Tocopherol or Vitamin E); also contain not commensurability vitamin E in many animals and plants food; vitamin E was found by U.S. scientist Herbert M Evans in nineteen twenty-two; be widely used as antioxidant equally; vitamin E belongs to liposoluble substance; be distributed in the cell membrane; content in endochylema is low; be mainly the oxidation of protection biological cell membrane, and pair cell water-soluble components protection effect is not good enough.All there are an obvious defects in vitamin C and vitamin E as antioxidant, and under certain conditions promptly, when for example the free iron ion being arranged in the cell, vitamin C can also cause peroxidation, may further damage the cellularity that those need protection.Novel antioxidant has melatonin; the English spelling of melatonin is found by U.S. scientist Aaron B Lerner in 1958 by (Melatonin); in human body, mainly secrete by the pineal gland in the brain; certain content is also arranged in the certain plants; at first be used to improve sleep; be widely used in antioxidation health food field after 1993 both at home and abroad; melatonin has the water fat dissolubility of holding concurrently; be distributed in the cellularity according to a certain percentage; can effectively protect the various structures of cell; make its damage of avoiding free radical, melatonin can not cause peroxidation simultaneously.The plain C and vitamin E and melatonin of giving birth to of dimension is antioxidant the most commonly used at present.
Summary of the invention:
Exist a kind of intrinsic interactive relationship between the different antioxidant, the simultaneously different distribution difference of antioxidant in cell, these two big characteristics based on antioxidant, the applicant is by in the theoretical analysis and experimental check, invented a kind of brand-new antibiont cell free-radical oxidation damage mixture, creativeness of the present invention just be to have caught the novel antioxidant melatonin can with classical antioxidant vitamin C, produce a kind of metabolism contact of intracellular interaction between the vitamin E, this metabolism contact can effectively suppress the peroxidation of vitamin on the one hand, on the other hand, can strengthen antioxidant capacity separately again each other, form a kind of mixture of antioxidation efficiently.The melatonin in this high-efficiency antioxidant mixture and the inner metabolism mechanism of vitamin are as follows: after vitamin E is disposed free radical on the cell membrane, make and form the vitamin E free radical, at this moment, vitamin C can provide an electronics to make the vitamin E free radical be reduced into the vitamin E of Wheat Protein again, and the vitamin C poison cell that loses an electronics is accepted the electronics that glutathione provides in starching, and is reduced into the vitamin C of anti-oxidation function again; Melatonin can both be removed free radical wherein in cell membrane and cytoplasm, lose an electronics then and form the melatonin free radical, vitamin C can provide an electronics to the melatonin free radical, make the melatonin that is reduced into anti-oxidation function, and the vitamin C free radical that loses an electronics is accepted the electronics that glutathione provides in cytoplasm, be reduced into the vitamin C of anti-oxidation function, so, in fact vitamin C, vitamin E and melatonin have formed a common antioxidant network in body, improved oxidation resistance separately greatly.In antioxidant network since melatonin can be in cytoplasm and cell membrane on uniform distribution, played the function served as bridge of vitamin E in vitamin C in the contact cytoplasm and the cell membrane.According to above theory analysis, the applicant has produced a creative thinking, clearly propose first, vitamin C, vitamin E, make up according to a certain percentage with melatonin, can form a kind of novel cell of antibiont efficiently free-radical oxidation damage mixture, to ending at present, by retrieval, still useless both at home and abroad vitamin C, vitamin E, three kinds of antioxidants of melatonin are formed a kind of novel anti biological cell free-radical oxidation damage mixture, and it is applied to damage with the biological cell free-radical oxidation report and the patent in relevant field as a kind of novel anti biological cell free-radical oxidation damage mixture.
Goal of the invention:
Each of this novel anti biological cell free-radical oxidation damage mixture formed part and is natural materials, they are widely used on market as the health food of antibiont cell free-radical oxidation damage respectively, so, this mixture can be used to prevent and treat previously described and cell free-radical oxidation damage diseases associated safely and efficiently, as nervous system degeneration (presenile dementia, the parkinson sexually transmitted disease (STD), sclerencephaly), apoplexy, cardiovascular disease (angina pectoris, myocardial ischemia, coronary atherosclerosis), tumor, the flexibility decrease of cataract and skin, wrinkle of skin, with be used for operation on heart, thrombolytic therapy, filed of organ transplantation, the nursing of skin and the radiotherapy of tumor, the support adjuvant drug of chemotherapy, and its effect is more much higher than using the arbitrary composition in the mixture separately, and can from following enforcement experiment, show, overcome the defective of a certain composition of independent use simultaneously again.
The specific embodiment:
The destruction of free-radical oxidation damage pair cell is many-sided; theory of medicine thinks that aforesaid many diseases are relevant with the destruction of radical pair cell; and theoretically and clear and definite explanation all arranged on the pathogenesis; the determination techniques of while with regard to the oxidative damage degree of radical pair cell also had sophisticated scheme; in other words, this novel anti biological cell free-radical oxidation damage mixture of the present invention to the anti-oxidation protection degree of human body cell also can science, measure reliably.At present with regard to the determination techniques of the cellular oxidation degree of injury of radical pair human body have multiple, as the autoxidizable mensuration of human body HbO2 Oxyhemoglobin A, beta-amyloid polypeptide 1-causes the mensuration of the mortality rate of neurocyte, lipid peroxidation is measured, free radical is measured or the like, and the present invention has selected preceding two kinds of determination techniques the most representative to finish embodiment of the present invention.
Human body HbO2 Oxyhemoglobin A is the main carrier of body delivery of oxygen, detect by spectrophotometer, human body HbO2 Oxyhemoglobin A has a main absworption peak in 575 nanosection, contained iron ion is positive divalent among the human body oxygenated blood red eggs A, so, HbO2 Oxyhemoglobin A be easy to environment in oxide, comprise hydrogen peroxide (H
2O
2), super oxide anion (O
2 -) react, produce autoxidation, originally the iron ion of positive divalent is oxidized to positive 3 valencys or positive 4 valencys, therefore, human body HbO2 Oxyhemoglobin A has lost the function of carrying oxygen, people's HbO2 Oxyhemoglobin A after the autoxidation descends in the optical density of 575 nanosection, be that human body HbO2 Oxyhemoglobin A autoxidation degree is high more, the human body HbO2 Oxyhemoglobin A of this oxidized mistake descends manyly more in the optical density of 575 nanosection, just be based on this principle, the present invention constantly adjusts vitamin C in this mixture, ratio between vitamin E and the melatonin three, through experiment and test repeatedly, in the hope of trying to achieve best of breed, with the optium concentration of using, experimental results show that vitamin C in this mixture, the ratio of vitamin E and melatonin is in 1: 1: 0.01 to 1: 1: 1 scope, and its concentration in human body HbO2 Oxyhemoglobin A all has certain oxidation resistance in 1-500 little scope of rubbing.
For the function to mixture of the present invention further confirms, this invention has also selected for use another to execute the solid yardage case, and promptly the nerve cell death that causes of beta-amyloid polypeptide 1--25-35 (A β 25-35) detects.MTT[3-(4 medically commonly used, 5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazoliumbromide] method measure to cultivate the mortality rate of neurocyte, can be used for judging the oxidation resistance of antioxidant and combination thereof, it is low more to have added the nerve cell death rate that after antioxidant or its combination β 25-35 is caused, the oxidation resistance of this antioxidant or its combination is strong more, the present invention has selected for use mice Hippocampus ascarid neurocyte (HT22) to carry out conventional neuronal cell cultures, and mice Hippocampus ascarid neurocyte is relevant with memory, and is very sensitive to the free radical loss.Through repeatedly experiment repeatedly, the present invention draws vitamin C in this mixture, vitamin E and melatonin three's ratio equally in 1: 1: 0.01 to 1: 1: 1 scope, the dense ability that 1-500 little scope of rubbing in all have certain antibiont cell free-radical oxidation damage of this antioxidation mixture in cell culture fluid.
Embodiment one:
The novel anti biological cell free-radical oxidation of forming with vitamin C, vitamin E, melatonin damages mixture; protect the experiment of human body HbO2 Oxyhemoglobin A autoxidation; vitamin C, vitamin E, melatonin, human body HbO2 Oxyhemoglobin A and other chemical substance are all available from (the Sigma Chemicals of U.S. Sigma chemical reagents corporation; St.Louis; MO, USA).
Experimental procedure:
One, with human body HbO2 Oxyhemoglobin A, be dissolved in the TRS-hydrochloride buffer, the molar concentration of buffer is 20 mMs, contains ethylenediaminetetraacetic acid 0.1 mM, acid-base value 7.4 (pH 7.4).The concentration of people's HbO2 Oxyhemoglobin A is 0.3 mg/ml, place 30 ℃ of constant water bath box temperature to bathe then, along with the prolongation of time, people's HbO2 Oxyhemoglobin A is autoxidation constantly, and its autoxidizable degree can be judged by its optical density in 575 nanometers of spectrophotometric determination.It is 8 groups that this experiment is divided into; Group 1 is the normal control group, and this group is not for adding people's HbO2 Oxyhemoglobin A of any reagent; Group 2 is the vitamin C processed group, and this group adds vitamin C 500 micromoles in through 1 milliliter of people's HbO2 Oxyhemoglobin A buffer of above-mentioned processing; Group 3 is the vitamin E processed group, and this group is for adding vitamin E 500 micromoles in process 1 milliliter of people's HbO2 Oxyhemoglobin A buffer of above-mentioned processing; Group 4 is the melatonin processed group, adds melatonin 500 micromoles in process 1 milliliter of people's HbO2 Oxyhemoglobin A buffer of above-mentioned processing; Group 5 is vitamin C and vitamin E processed group, vitaminize C, each 500 micromole of vitamin E in process 1 milliliter of people's HbO2 Oxyhemoglobin A buffer of above-mentioned processing; Group 6 is vitamin C and melatonin processed group, adds vitamin C, each 500 micromole of melatonin in process 1 milliliter of people's HbO2 Oxyhemoglobin A buffer of above-mentioned processing; Group 7 is vitamin E and melatonin processed group, adds vitamin E, each 500 micromole of melatonin in the buffer solution at 1 milliliter of people's HbO2 Oxyhemoglobin A through above-mentioned processing; Group 8 is vitamin C, vitamin E, melatonin processed group, and this group is for adding vitamin C, vitamin E, each 500 micromole of melanocyte in process 1 milliliter of people's HbO2 Oxyhemoglobin A buffer of above-mentioned processing.Measure the light absorption density of people's HbO2 Oxyhemoglobin A of 8 groups of samples with one milliliter polyethylene color comparison tube in 575 nanosection, its value will be carried out the reference standard of the respective sets after temperature is bathed as 8 groups of samples; After then 8 groups of people's HbO2 Oxyhemoglobin A buffer temperature of various combinations being bathed 20 hours, with one milliliter polyethylene color comparison tube in 575 nanosection, measure the light absorption density of people's HbO2 Oxyhemoglobin A of each group, the optical density value of bathing each preceding respective sets with temperature is 100%, repeat 6 independently tests in this way, again data value of averaging of each result is added and subtracted the statistical disposition of standard error, the method of statistical disposition is variance analysis (ANOVA) and t-check, and p＜0.05 is considered to exist on the statistics significant difference.The result of statistical disposition as shown in Table 1, table one be antioxidant and the combination to the influence statistical table of human body Yang He Xue Red egg from the A oxidation, the number in the table is meansigma methods ± standard error; N=6; * for compare P＜0.05 with matched group; * is for comparing P＜0.01 with matched group; * is shown the percentage of decay % of optical density in 575 nanosection for comparing P＜autoxidizable table of degree of 0.01. human body Yang He Xue Red egg A with other experimental group.As can be seen from Table I, the optical density of people's HbO2 Oxyhemoglobin A in 575 nanometer light districts of first group of specimen descended about 14%, added vitamin C respectively, vitamin E, and the people's autoxidation hemoglobin A that has added in the specimen of vitamin C and vitamin E mixture has descended between 17%～24% in the optical density of 575 nanosection separately, shown that vitamin C-vitamin E may produce peroxidation, because having free iron ion disengages in people's HbO2 Oxyhemoglobin A, only descended 13% and added the optical density of specimen that melatonin handled in 575 nanometer light districts, compare no statistical discrepancy with first group result.At vitamin C; the optical density of people's HbO2 Oxyhemoglobin A in 575 nanometer light districts in vitamin E and the blended specimen of melatonin three only descended about 5%; compare with first group and other each experimental result of organizing; exist significant difference on the statistics; experimental result proves; by vitamin C; the mixture of vitamin E and melatonin three combination has powerful antioxidation; not only can significantly reduce the autooxidation of people's HbO2 Oxyhemoglobin A; can also suppress vitamin C; the peroxidation of vitamin E; protect the complete of people's HbO2 Oxyhemoglobin A structure, experimental result and theoretical direction expection are very identical.
Embodiment 2:
Vitamin C, vitamin E and melatonin make up the experiment of the protective effect of the nerve cell death that the beta-amyloyd polypeptide is caused.
1, cell culture and processing: mice hippocampal neurons (HT22 cell strain) is incubated in the DMEM culture fluid, contain 10% calf serum in this culture fluid, the paddy amine of 2 mMs, company's enzyme element of every milliliter 100 unit, 0.2 milligram the cephalo enzyme element and the HEPEBS of 25 mMs.The cell kind is grown to the culture plate in 96 holes, and cell density is 10,000/ square centimeters, puts into 5% carbon dioxide cell incubator (37 ℃) and cultivates 12 hours; Add different reagent behind cell attachment again, it is 9 groups that experiment is divided into, and group one is the normal control group, does not add any reagent, and group 2 to group 9 is a test group, at first adds vitamin C 50 micromoles in group 3; Group 4 adds vitamin E 50 micromoles; Organize 5 melatonin, 50 micromoles; Group 6 adds vitamin C and each 50 micromole of vitamin E; Group 7 adds vitamin C and each 50 micromole of melatonin; Group 8 adds vitamin E and each 50 micromole of melatonin; Group 9 adds each 50 micromole of vitamin Cs, vitamin E and melatonin, cultivates in incubator after 1 hour, adds neurovirulent beta-amyloid polypeptide 1--25-35 (A β 25-35) 30 micromoles from organizing 2 separately to group 9, continues to cultivate 24 hours.
2, the analysis of cell survival rate: MTT[3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide] method is used for the analysis of cell survival rate, MTT 0.5 mg/ml (final concentration), be added to the cell after the processing, continuation was cultivated in incubator 4 hours, add lysate (20% sodium dodecyl sulfate then, 50%N, N-DIMETHYLFORMAMIDE, Ph 4.7), put into 37 ℃ of degree constant water bath box temperature and bathed 18 hours, the culture plate with 96 holes places culture plate reading apparatus (μ Quant then, Bio-Tek Instruments Inc.Winooski, VT USA) reads counting in 570 nanosection, and the count value of control cells is 100% (cell survival rate).
3, result: A β 25-35 is a neurotoxin, is the Main Ingredients and Appearance that forms alzheimer disease brain characteristic pathological changes senile plaque; The deposition of A β 25-35 in brain produces a large amount of free radicals, causes cyto-architectural oxidative damage, finally causes the death of neurocyte.Result from this experiment as can be seen, 30 micromolar amyloid polypeptides have caused the neurocyte oxidative damage of cultivating, within 24 hours, 60% nerve cell death (survival rate is 40%) is arranged, in the experiment, select 3 kinds of antioxidants of critical valid density for use, comprised classical antioxidant vitamin C, vitamin E and novel antioxidant melatonin.Single antioxidant and two kinds of antioxidants share, and compare with group 2, can slightly improve the survival rate (survival rate is 45%-55%) of cell.And, prevented the neurocyte toxicity that A β 25-35 causes fully with the combination of vitamin C, vitamin E and 3 kinds of materials of melatonin.Make the neurocyte survival rate of cultivation the same, reached 100% with matched group.Its result such as table two, table two are antioxidant and the statistical table that makes up the protective effect effect of the nerve cell death that beta-amyloid polypeptide 1--25-35 (A β 25-35) is caused thereof, and the numerical value in the table is meansigma methods ± standard error; N=6; The method of statistical disposition is variance analysis (ANOVA) and t-check, and p＜0.05 is considered to exist on the statistics significant difference, and * is for comparing P＜0.05 with matched group; * is for comparing P＜0.01 with matched group; * is for to compare P＜0.01 with other experimental group.Except that matched group, other experimental group all is added with A β 25-35 reagent 30 mMs; Antioxidant is 50 mMs, shows in the table two that the combination of vitamin C, vitamin E, three kinds of materials of melatonin can be brought into play antioxidation efficiently in the neurocyte of cultivating.Synergism has taken place in three's combination, makes its antioxidative effect multiplication.
This novel anti biological cell free-radical oxidation damage mixture of the present invention is useful as a kind of health food to human beings'health, particularly to above-mentioned some treatment of diseases and control, to the aftertreatment of some operation and prolong the transplant organ that exsomatizes and store with haulage time and all have wide practical use.Each composition all has sophisticated consumption as a kind of health food at home and abroad at present in the efficient oxidation mixture, according to these consumptions, the ratio of three kinds of compositions in again according to the present invention, it is to need with the person at every turn with 603 milligrams as the consumption of health food that the present invention recommends this mixture, there are 300 milligrams and contain vitamin C in 603 milligrams, 3 milligrams of 300 milligrams of vitamin Es and melatonin, once a day, need usefulness person can be with oral, oral available tablet, also available capsule or oral liquid, but also intramuscular injection, several different methods such as intravenous injection, simultaneously also can cream fat etc. form directly be coated in and use on the skin, as the nursing and the cosmetic product of skin, simultaneously, this mixture can be developed further into medicine, be used for and the relevant field of biological cell free-radical oxidation damage, this invention will be to promoting that human beings'health plays a positive role.
Table one: antioxidant and combination thereof are to the statistical table that influences of human body Yang He Xue Red protein A oxidation
| Antioxidant combination | 575 nanometers optical density decay % |
| Matched group | 14±0.8 |
| The vitamin C group | 18±1.2 * |
| The vitamin E group | 20±1.3 * |
| The melatonin group | 13±1.1 |
| Vitamin C and E combination group | 24±1.5 * |
| Vitamin C and melatonin combination group | 18±1.5 * |
| Vitamin E and melatonin combination group | 17±1.4 * |
| Vitamin C and E add melatonin combination group | 6±0.7 **## |
Number in the table is meansigma methods ± standard error; N=6;
*Be P＜0.05 compared with the control;
*Be P＜0.01 compared with the control;
##For the table of degree of comparing P＜white oxidation of 0.01. human body Yang He Xue Red egg A with other experimental group is shown the decay % of optical density in 575 nanosection, antioxidant is 500 mMs.
Table two: the statistical table of the protective effect effect of the nerve cell death that antioxidant and combination thereof cause beta-amyloid polypeptide 1--25-35 (A β 25-35)
| Antioxidant and combination thereof | Neurocyte survival rate % |
| Matched group | 100±8.2 |
| Aβ25-35 | 40±6.0 |
| The vitamin C group | 45±5.5 |
| The vitamin E group | 46±7.4 |
| The melatonin group | 46±5.8 |
| Vitamin C and vitamin E combination group | 58±7.7 * |
| Vitamin C and melatonin combination group | 60±8.4 * |
| Vitamin E and melatonin combination group | 57±6.7 * |
| Vitamin C and vitamin E add melatonin combination group | 100±6.5 **## |
Numerical value in the table is meansigma methods ± standard error; N=6;
*For compare P＜0.05 with matched group;
*For compare P＜0.01 with matched group;
##For comparing P＜0.01. except that matched group with other experimental group, other experimental group all is added with A β 25-35 reagent 30 mMs; Antioxidant is 50 mMs.
Claims (5)
1, a kind of novel anti biological cell free-radical oxidation damage mixture of the present invention is characterized in that this mixture is made up of melatonin and vitamin substances.
2, a kind of novel anti biological cell free-radical oxidation damage mixture according to claim 1 is characterized in that this mixture is made up of the vitamin C in melatonin and the vitamin substances, vitamin E.
3, according to the described a kind of novel anti biological cell free-radical oxidation damage mixture of claim 1, it is characterized in that vitamin C in this mixture, vitamin E, melatonin three's proportion of composing all has antibiont cell free-radical oxidation damaging action in 1: 1: 0.001 to 1: 1: 1 scope.
4, the composition that it is characterized in that vitamin C, vitamin E, melatonin in this mixture according to the described a kind of novel anti biological cell free-radical oxidation damage of claim 1 mixture has very strong antibiont cell free-radical oxidation damaging action in 1: 1: 0.01 ratio.
5,, it is characterized in that this mixture can be used for and the relevant medicine of biological cell free-radical oxidation damage, medical treatment, health food, fields such as cosmetics according to the described a kind of novel anti biological cell free-radical oxidation damage mixture of claim 1.
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| CN104721184A (en) * | 2015-02-16 | 2015-06-24 | 中国农业大学 | Preparation capable of improving cow conception rate as well as preparation method and application of preparation |
| CN104784171A (en) * | 2015-02-16 | 2015-07-22 | 中国农业大学 | Composite anti-oxidation preparation for reducing livestock somatic cell count, preparation method and applications thereof |
| CN116270618A (en) * | 2023-05-05 | 2023-06-23 | 中国人民解放军海军军医大学第一附属医院 | Melatonin and vitamin E pharmaceutical composition and application thereof |
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| CN101199273B (en) * | 2006-12-13 | 2011-04-13 | 谭敦宪 | Novel multiple organs storage protection liquid |
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| JP2000143546A (en) * | 1998-11-16 | 2000-05-23 | Hiroshi Wada | Suppressant for oxidative decomposition of melatonin |
| CN1272322A (en) * | 1999-10-25 | 2000-11-08 | 潘君琦 | Middle-aged and old people brain platinum albumin milk |
| US6689385B2 (en) * | 2000-11-03 | 2004-02-10 | Chronorx Llc | Formulations for the treatment of insulin resistance and type 2 diabetes mellitus |
| CN1368383A (en) * | 2001-02-09 | 2002-09-11 | 济南百伦思营养食品有限公司 | Precision and preparing process of health-care compound hormone product |
| DE10110418A1 (en) * | 2001-03-05 | 2002-09-12 | Asat Ag Applied Science & Tech | Melatonin Vitamin A supplements |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104721184A (en) * | 2015-02-16 | 2015-06-24 | 中国农业大学 | Preparation capable of improving cow conception rate as well as preparation method and application of preparation |
| CN104784171A (en) * | 2015-02-16 | 2015-07-22 | 中国农业大学 | Composite anti-oxidation preparation for reducing livestock somatic cell count, preparation method and applications thereof |
| CN104784171B (en) * | 2015-02-16 | 2017-06-13 | 中国农业大学 | A kind of compound anti-oxidation preparation for reducing domestic animal somatic number and preparation method and application |
| CN116270618A (en) * | 2023-05-05 | 2023-06-23 | 中国人民解放军海军军医大学第一附属医院 | Melatonin and vitamin E pharmaceutical composition and application thereof |
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