CN102600203A - Medicine composition for preventing or curing degenerative disease caused by oxidative stress - Google Patents
Medicine composition for preventing or curing degenerative disease caused by oxidative stress Download PDFInfo
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Abstract
The invention discloses a cell optimizing medicine composition for preventing or curing a degenerative disease caused by oxidative stress, which comprises one or more types of proper quantities of effective bioelements, one or more types of antioxidant with effective dose, and one or more types of pharmaceutically acceptable carriers. The medicine composition not only contains effective antioxidant ingredients capable of clearing away radical and protecting DNA (deoxyribonucleic acid), protein and lipid against being injured, but also contains a trace element combination required for normal cell growth. The medicine composition has wide and excellent preventing and curing potency for the degenerative disease caused by oxidative stress, and has outstanding functions of high-efficient radical elimination activity and stability, few side effects in organisms, high safety and the like.
Description
Technical field
The present invention relates to cell and optimize the field, more particularly, relate to the pharmaceutical composition of the degenerative disease preventing/treating that oxidative stress causes.
Background technology
Body aging (claiming aging again) is the general performance of human body at degeneration function reduction in period and physiologic derangement.The physiological aging performance comprises that body fat increases; Protein reduces; Total liquid measure reduces in the body; The liver function decline; And the decline of digestive system, respiratory system, cardiovascular system, urinary system, nervous system and hormonal system function.
Medical circle and biosphere have proposed more than the 200 kind of theory about aging so far, summarize to get up for setting forth old and feeble mechanism from organ level and cellular level.
I. organ senescence mechanism
Nerve, endocrine, immune system are the key factors that body self is regulated, and the three interacts through the active substance that produces separately and regulates that to keep organismic internal environment relatively stable.
Neuroendocrine system (hypothalamus, hypophysis, target gland and tissue) is most important to keeping of body development and function, is determining that simultaneously tissue metabolism leads, thereby participates in the aging adjusting that reaches the life-span of bodily tissue.In the body aging process, the neuron of each nuclear group of hypothalamus presents losing in various degree age with increasing, and its contained mediator also has change in various degree, causes endocrine function not enough, thereby promotes body aging.
Hormonal system is mainly regulated growth promoter and the aging course of animal through hormone.In the ageing process, the change of endocrine function shows as the receptor in target cell minimizing and reactivity goes down; The hormone degradation rate lowers, and makes the corresponding rising of this hormone concentration in the blood to cause this hormone secretion to reduce through feedback mechanism; The neuroendocrine regulatory function of enzymatic synthesis goes down.Obstacle also takes place in the interaction between the endocrine gland simultaneously, thereby causes each systemic-function that complicated change takes place.Change and be apparent that gonad most.Reproductive performance and gonadal hormone generative capacity descend when old and feeble.The adrenal androgen secretion reduces half the, even complete obiteration; Parathyroid function descends, and hormone secretion reduces, and the secretory reaction of low blood calcium is also descended.
Among the human aging process, the variation that the formation of immunocyte takes place comprises: T, B cell absolute value obviously reduce, and its subgroup also changes.Immunologic function degression: the T cell descends to the multiplication capacity of mitosis primary stimuli, and the B cell reduces external antigen-reactive ability and the autoantigen respond is increased; The NK cytoactive obviously descends.Cytokine that immunocyte produces such as IL-2, the active decline of IFN-r, IL-6, TGF-B (B-transforming growth factor), IL-10 also have obvious change in ageing process.Above-mentioned variation causes immunologically competent cell to antigenic meticulous identification ability decline, accuracy controlling miopragia; And immunne response is disorderly, poor efficiency and invalid; Make immune three big functions (defence, from steady, keep watch on) lack of proper care or weaken, finally cause the incidence rate of old people's infectious disease, autoimmune disease and cancer obviously to increase.
Table-1; Old people and youngster leukocyte crowd are relatively
| Cell mass | Youngster | The old man |
| Total white blood cells/mm 3 | 4927 ± 36 | 3993 ± 222 |
| Mononuclear cell number/mm 3 | 278 ± 25 | 290 ± 39 |
| Lymphocyte number/mm 3 | 1679 ± 136 | 1375 ± 116 |
| Fc recipient cell/mm 3 | 121 ± 19 | 176 ± 23 |
| FcR-PBL% | 7.7 ± 1.3 | 12.8 ± 1.4 |
| T cell number/mm 3 | 1019 ± 103 | 734 ± 79 |
| T cell-PBL% | 59.5 ± 30 | 53.1 ± 25 |
| Th cell number/mm 3 | 50 ± 9 | 69 ± 11 |
| Th-T cell % | 4.5 ± 0.6 | 10.4 ± 1.3 |
| PHA IR (cpm) | 33257 ± 2673 | 17777 ± 2000 |
II. oxidative stress mechanism
(Oxidative Stress OS), refers to that body is under the condition of internal and external environment destructive stimulus to oxidative stress; Produce reactive oxygen free radical (Reactive Oxygen Species in the body; ROS) and the active nitrogen free radical (Reactive Ntrogen Species RNS) produces too much, and degree of oxidation exceeds the removing of oxide; Oxidative system and antioxidant system are unbalance, the physiology of caused cell and tissue and pathological reaction.Oxygen-derived free radicals can penetrate
Cell membraneGet into
Nucleus, the macromolecular substances such as DNA, protein and lipid in the challenge organism cause the damage of cellular oxidation property, such as oxidable DNA; Make its fracture or sudden change, dna replication dna with transcribe be obstructed (Rueff, J.; Et al. Mutation Res., 289:197-204,1993/Sankaranarayanan; K. Mutation Res., 258:75-97,1991.).In case it is terminal that the dna single chain interruption that ROS causes betides the chromosome petiolarea, then petiolarea shortens quickening.ROS damages petiolarea, possibly cause the SAG sudden change, thereby causes the confusion of whole life generation systems property.The various cellularity relevant with aging and the variation of function finally are to be caused by the structure of gene and the change of regulation and control level.
A large amount of evidences support that oxidative stress is this viewpoint of core mechanism that causes improper aging.The nearly all organ of human body all is easy to receive the injury that oxidative stress brings, and descended by its cell function that influences is organ senescence, atrophy, hypothyroid basic reason, is the common ground of person in middle and old age's degenerative disease morbidity.Common person in middle and old age's degenerative disorders includes but not limited to:
1. hormonal system: hormone secretion minimizing, climacteric syndrome, diabetes etc.
2. central nervous system: insomnia, dementia, Ba Jinsen disease
3. sensory system: visual deterioration, cataract, hearing loss
4. cardiovascular system: arrhythmia, hypertension, arteriosclerosis, coronary heart disease, heart failure
5. respiratory system: Chronic obstructive pulmonary disease, emphysema
6. urinary system: chronic kidney depletion, prostate hyperplasia, chronic prostatitis
7. skeletal musculature: muscle weakness, edema, osteoarthritis, osteoporosis
8. digestive system: the gastrointestinal ability drop, digestion, absorption function weaken constipation etc.
9. liver function system: hepatocyte dwindles, hardening, and function of detoxification, albumen synthesis capability reduce
According to thinking, dropping to oxidative stress minimum is crucial for prevention and treatment person in middle and old age degeneration.Epidemic data shows that antioxidant (Antioxidants) provide great benefit in this field.
Antioxidant is the molecule that can slow down or stop other molecular oxidations.Antioxidant stops oxidative chain reactions through removing free radical intermediate, and himself suppresses other oxidation reactions through oxidation.Reducing agent is mercaptan or expect to have anti-oxidation characteristics usually for example more.The antioxidant for clearing free radical also protects DNA, protein and lipid to avoid damage.But existing antioxidant has active in vivo evanescence, and easily promptly by metabolism to external, can not give full play to free radical and eliminate defectives such as effect.
Summary of the invention
The technical problem that the present invention mainly solves provides and a kind ofly is used to prevent or treat the cell of the degenerative disease that oxidative stress causes to optimize pharmaceutical composition, can fill up the carcinogenic or intensive physiological side effects that a) hormonotherapy accompanied in treatment person in middle and old age degenerative disease at present; B) the active in vivo evanescence of common antioxidant, and easily promptly by metabolism to external, can not give full play to free radical and eliminate defectives such as effect.
For solving the problems of the technologies described above; The technical scheme that the present invention adopts is: a kind of pharmaceutical composition is provided; Be used to prevent or treat the degenerative disease that oxidative stress causes; Said pharmaceutical composition comprises: the effective bioelement of an amount of one or more, one or more antioxidants of effective dose, one or more pharmaceutical carriers.
In preferred embodiment of the present invention, said bioelement comprises one or more the mixing in its pharmaceutically useful salt, active fat, active metabolite and its derivant.
In preferred embodiment of the present invention, said antioxidant comprises one or more the mixing in its pharmaceutically useful salt, active fat, active metabolite and the derivant thereof.
In preferred embodiment of the present invention, the effective bioelement of wherein an amount of one or more is selected from hydrogen (H), carbon (C), nitrogen (N), oxygen (O), fluorine (F), sodium (Na), magnesium (Mg), silicon (Si), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), ferrum (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), bromine (BR), molybdenum (Mo), stannum (Sn) and iodine (I).
In preferred embodiment of the present invention, one or more antioxidants of said effective dose comprise non-enzyme antioxidant.
In preferred embodiment of the present invention, said non-enzyme antioxidant, comprise tocotrienol, glutathion,
MelatoninAnd alpha-lipoic acid.
In preferred embodiment of the present invention, one or more antioxidants of said effective dose comprise one or more antioxidases.
In preferred embodiment of the present invention, said antioxidase comprises superoxide dismutase, catalase and glutathion peroxidase.
In preferred embodiment of the present invention, the mass percent that said polyphenoils and biologic trace element account for said pharmaceutical composition is 0.01-50 %.
In preferred embodiment of the present invention, the mass percent that said polyphenoils and biologic trace element account for said pharmaceutical composition is 2-20%.
In preferred embodiment of the present invention, wherein the amount of bioelement and the ratio of the amount of antioxidant are from every gram bioelement 1, and 000IU is to every gram antioxidant 1,000,000IU.
In preferred embodiment of the present invention, wherein the amount of antioxidant and the ratio of the amount of bioelement are from every gram antioxidant 1, and 000IU is to every gram bioelement 1,000,000IU.
The invention has the beneficial effects as follows: pharmaceutical composition of the present invention; Not only contain and have the removing free radical; Effective antioxidant content that protection DNA, protein and lipid are avoided damaging contains the required trace element combination of cell normal growth, data show simultaneously; Exist intensive synergism between cell biological element and the antioxidant, use antioxidant the antioxidation stress that trace element provided required to compare and to significantly improve simultaneously with independent use antioxidant with containing the cell normal growth.The degenerative disease that this pharmaceutical composition causes for oxidative stress has extensive and excellent prevention and treatment is renderd a service: (I) have free radical elimination activity and stability, the high outstanding function of (II) few side effects, safety in vivo efficiently.
The specific embodiment
Set forth in detail in the face of preferred embodiment of the present invention down, thereby protection scope of the present invention is made more explicit defining so that advantage of the present invention and characteristic can be easier to it will be appreciated by those skilled in the art that.
The present invention's problem to be solved provides safety, person in middle and old age's degenerative disease that stable and effective antioxidation combination is caused by oxidative stress in order to prevention and treatment.
Can be used for compositions of the present invention and must have following characteristic: when using to the patient, can not cause significant adverse side effect, and not cause the loss of activity of one or more components with one or more component reaction of compositions with the amount that is used as antioxidant.Preferably those are present in human body and/or naturally available from the material or derivatives thereof of plant or animal.Preferred, be used for antioxidant composition of the present invention and must have and the synergistic drug regimen of bioelement.
For solving said problem, research worker of the present invention has been carried out the various medicaments experiment.The result finds that polyphenoils combination and biologic trace element combination with cytoprotection hereinafter described have comprehensive cell optimization function, and pair cell damages or cell death is inhibited.Also find simultaneously, this combination agent good stability, toxicity is low in vivo, can give full play to effect, thereby has accomplished the present invention.
(1) the primary component of the present invention is an anti-oxidant compositions.The material that can be used as antioxidant of the present invention is that those demonstrate antioxidant activity and do not cause significant adverse side effect when using to the patient; The use amount of said antioxidant can effectively provide sufficient antioxidant activity, and does not cause the remarkable loss of one or more composition activities with one or more component reaction of said composition.The preferred antioxidant composition of the present invention has following characteristic:
1. antioxidant composition contains superoxide dismutase (Superoxide dismutase SOD)
Superoxide dismutase (Superoxide dismutase SOD) is a kind ofly can the catalysis superoxides to be converted into the enzyme of oxygen and hydrogen peroxide through dismutation reaction, can remove superoxides, and the protection cell is avoided oxidative damage.
SOD mainly is present in Cell sap and the mitochondrial matrix, defending organism body oxidative damage.SOD can be converted into hydrogen peroxide and molecular oxygen by the catalysis superoxide radical, suppresses the apoptosis of some cells, in resisting the cell injury that oxygen-derived free radicals causes, plays a crucial role.
2. antioxidant composition, contain simultaneously catalase (Hydrogen peroxidase) claim again catalase (Catalase, CAT).CAT is a kind of intravital terminal oxidase of all kinds of biologies that extensively is present in, and with the superoxide dismutase synergism, prevents the injury of radical pair cell.Superoxide dismutase (SOD) converts deleterious superoxide radical to hydrogen peroxide, converts thereof into harmless water and oxygen by catalase again.CAT is one of enzyme the most effectively in the cell, and each catalase molecule can be changed the hydrogen peroxide molecule of millions of meter each second.
Hydrogen peroxide is the spontaneous destructive refuse of a kind of dependence oxygen existence organism in the human body.It converts fatty acid into energy at human body, produces when leukocyte attack and killing bacteria.Catalase is positioned at the peroxisome of cell, and it stops the process of hydrogen peroxide injury cell, and prevents that hydrogen peroxide is converted into hydroxy radical (a kind of can the attack, even a bad actor who causes the DNA variation).
Catalase makes the toxicant inactivation, regulates the concentration of oxygen, and the metabolism that oxidation of fat acid reaches nitrogen substance makes it become one of key enzyme of biological defensive system.
3. antioxidant composition contains simultaneously
Glutathion peroxidase(Glutathione Peroxidase; GSH-Px/GPx)
Glutathion peroxidase (GSH-Px) is one of antioxidase important in the living organism.It plays a role with the form of selenocysteine (Sec), is that Reducing agent decomposes intravital MDA with glutathion (GSH), thereby can prevent that cell membrane and other biological tissue from avoiding peroxide injury.It has constituted the anti-oxidative defense system of body with intravital superoxide dismutase (SOD) and catalase (CAT).
Selenium is the only element that plays the redox catalysis effect among the GSH-Px; (form SeH) plays a role with selenium hydrogen base; In catalytic process, exist a valence state circulation; When hydroperoxides were excessive, it was superoxide dismutase (SOD) that there is (E2SeOOH) the first line of defence in enzyme active center selenium with the selenic acid form, and it is converted into hydrogen peroxide and other hydroperoxides with O-2; Defence line, second road is catalase (CAT) and GSH-Px, and wherein CAT can remove the H2O2 in the oxygen system, and GSH-Px is distributed in the cytosol and mitochondrion of cell, can remove H2O2 and hydroperoxides simultaneously.
GSH-Px enzyme owner will comprise 4 kinds of different GSH-Px, is respectively endochylema GSH-Px (cGSH-Px), blood plasma GSH-Px (pGSH-Px), phospholipid hydroperoxide GSH-Px (phGSH-Px) and gastrointestinal tract GSH-Px (giGSH-Px).
(cGSH-Px) extensively be present in each tissue in the body serves as maximum with the liver erythrocyte to endochylema GSH-Px.Its physiological function mainly is that catalysis GSH participates in peroxidization, removes the peroxide and the hydroxy radical that in the Cellular respiration metabolic process, produce, thereby alleviates cell membrane
Polyunsaturated fatty acidPeroxidation.
Blood plasma GSH-Px (pGSH-Px) mainly be distributed in the blood plasma, its function also is not very clear at present, but the outer hydrogen peroxide of verified and scavenger cell is relevant with the transportation of participating in GSH.
(phGSH-Px) mainly be present in the testis also has a small amount of distribution to phospholipid hydrogen peroxide GSH-Px in other tissue.Its biological function is to suppress the membrane phospholipid peroxidating.
(giGSH-Px) only be present in the gastrointestinal tract of rodent, its function is to watch for animals to avoid taking in to gastrointestinal tract specificity GPX-Px
MDAInfringement.
4. cell optimum organization thing contains non-enzyme antioxidant simultaneously, comprise tocotrienol, glutathion,
MelatoninAnd alpha-lipoic acid.
4.1 tocotrienol (Tocotrienols) is fat-soluble
Antioxidant, mainly be present in the cell membrane, have to imitate and suppress LDL oxidation and endotheliocyte lipid peroxidation.In liver microsomes, in iron ion/Ascorbate and the inductive lipid peroxidation of iron ion/NADPH, the antioxidant activity of tocotrienol is 40～60 times of α-tocopherol.Tocotrienol can be removed free radical, and can in lipid peroxidation, suppress the generation of hydrogen peroxide and alkoxyl.
Lp (a) is a kind of lipoprotein that is present in the blood plasma.Increasing of Lp in the blood plasma (a) can cause atherosclerosis or thrombosis.Conventional medicine is difficult to reduce the content of Lp (a) in the blood plasma.Yet tocotrienol but can make the level of Lp (a) reduce by 17%.Tocotrienol also has the effect that cholesterol reducing, LDL-C and antithrombotic formed and reduced platelet aggregation.
4.2 glutathion (Glutataione)
Be a kind ofly to contain by what three aminoacid were formed
SulfydrylSmall-molecular peptides, have important anti-
OxidationEffect and integration
DetoxifcationEffect.
The major physiological effect of glutathion is important antioxidants and a free radical scavenger in the body, as combining with free radical, heavy metal etc., thereby is converted into harmless material to deleterious poisonous substance in the body, excretes external.
Reduced glutathion can be protected many
ProteinWith in the enzyme equimolecular
SulfydrylNot by like harmful substance oxidations such as free radicals, thereby make protein and its physiological function of enzyme equimolecular performance.The content of glutathion is a lot of in the human erythrocyte, and this is in reducing condition to proteinic sulfydryl on the protection erythrocyte membrane, prevents that haemolysis is significant, but also can protect
HemoglobinThereby do not receive oxidations such as hydrogen peroxide oxidation, free radical to make it continue the ability of normal performance oxygen therapy.
Glutathion is all right
Improve body immunity, promote blood cell, reduce the total content of inflammation material in the body, delaying cell aging.With
VitaminUnder the co-administered condition of C and alpha-lipoic acid, glutathion just can be brought into play its pharmacological function effectively.
4.3
Melatonin(Melatonin)
MelatoninMainly by the mammal and the mankind
PinusA kind of amine bormones that produces has hypnotic, anti-
Old and feeble, regulate immunity, anti-
TumorEtc. multinomial physiological function.
Melatonin passes through to remove free radical,
AntioxidationWith the peroxidization protection cellularity that suppresses lipid, prevent DNA damage, reduce the content of body endoperoxide.Melatonin causes that to safrole (a kind of through discharging free radical the carcinogen of damage dna) protective effect of DNA damage can reach 99%.There are tangible antagonism in the peroxidating that melatonin causes exogenous poisonous substance and the tissue injury that free radical caused of generation.Melatonin can also reduce the content of LPO in the brain, and zones of different such as cerebral cortex, XIAONAO, Hippocampus, hypothalamus, striatum that it acts on brain etc. located, and is identical basically, and all is dose-dependence.
4.4 alpha-lipoic acid (Alpha Lipoic Acid)
Alpha-lipoic acid is a kind of antioxidant that is similar to vitamin, but its oxidation resistance is ascorbic 200 times.The 400-600 of vitamin E doubly.Thioctic acid is a kind of mitochondrial ferment that is present in; It not only can be dissolved in fat but also can be water-soluble; Can arrive any one cell position and have more comprehensively protective effect; And active force also comes lastingly than other antioxidant, therefore is called as " super antioxidant ", is a kind of antioxidant of " function is maximum and activity is the strongest " in all antioxidants.Alpha-lipoic acid can be reduced into the state of activation with some deactivated antioxidants (like vitamin C, vitamin E, glutathion and coenzyme Q10) and make it reusable edible, strengthens antioxidation; Impel human body to produce coenzyme Q10, required for heart oxygen supply and Conversion of energy, be a kind of effective heart protective agent, can also enhances human body antioxidant system and function of immune system; Alpha-lipoic acid can also strengthen the utilization of type ii diabetes patient to glucose, suppresses glycosylation (changing into proteinic unusual product by sugar).
(2) another important component of the present invention is to optimize the bioelement of cell.The typical material of optimizing cell is a trace element.The optimum organization of this cell contains 27 kinds of cells necessary bioelement (comprising trace element) hydrogen (H) of growing; Carbon (C); Nitrogen (N); Oxygen (O); Fluorine (F); Sodium (Na); Magnesium (Mg); Silicon (Si); Phosphorus (P); Sulfur (S); Chlorine (Cl); Potassium (K); Calcium (Ca); Vanadium (V); Chromium (Cr); Manganese (Mn); Ferrum (Fe); Cobalt (Co); Nickel (Ni); Copper (Cu); Zinc (Zn); Arsenic (As); Selenium (Se); Bromine (BR); Molybdenum (Mo); Stannum (Sn) and iodine (I).
The basic effect of bioelement is for the cell growth essential energy and nutrient to be provided.Though constant that the cell normal growth is required and trace element are atomic at the intravital content of people, have huge biological action.Their major physiological function has:
I. the conveying of oxygen in the body, as contain Ferri-hemoglobin the oxygen therapy function is arranged.
II. the constituent of various enzymes and activator in the body.Over thousands of kind of enzyme mostly contains one or more trace metal ions in the known body.Can activate the intestinal phosphatase enzyme like zinc, liver, kidney peroxidase are again that insulin synthesis institute is essential; Manganese ion can activate arginase and acetylcholine esterase etc.; Cobalt is one of constituent of vitamin B12, or the like.As losing metal, the vigor of cell will extremely descend, even forfeiture.
III. participate in the secretion of hormone, regulate important physiological function.Be one of important component of thyroxin like iodine, in-vivo iodine deficiency then body can not the synthetic thyroid hormone, will influence body homergy and growth promoter.
IV. be the formation part of hereditary material nucleic acid.Nucleic acid is the carrier of hereditary information, and it contains the quite high trace element of concentration, like chromium, cobalt, copper, zinc, nickel, vanadium etc.These elements all have material impact to the duplicating of structure, function and DNA (DNA) of nucleic acid.
V. participate in metabolism--biologic trace element has been participated in the activity of oxidation-reduction system in the human body; Make the material produce power that stores in the cell; And utilize this energy; Play metabolic effect, the content of most of biologic trace elements reduces with age growth, and this explanation has direct relation with aging.
Exist dual substantial connection between trace element and oxidative stress simultaneously.On the one hand, trace element can produce active oxygen and intermediate product free radical in the metabolic process in vivo; The transition metal trace element can promote active oxygen to generate like iron ion, copper ion.On the other hand, in the cell competent trace element (with other nutrients) but the anti-oxidative defense function of enhancing body; Some trace element can be brought into play antioxidation directly or indirectly.Have data to show, the highest mammiferous life time is relevant with the concentration of some trace element of blood plasma and anti-oxidizing compounds, and they possibly be the factor of determinations of high life time.
When compositions of the present invention was used to the patient, the use amount of its antioxidant ingredients can effectively provide significant antioxidant activity, and the amount of application of its trace element component can effectively provide biological metabolism required normal nutrient for cell.
Drug regimen of the present invention has aforesaid characteristic: in cell optimization of the present invention and degenerative disease prophylactic treatment compositions, effective ingredient or useful component are aforesaid two types of polyphenoils, and one type is the enzyme antioxidation, comprises
Superoxide dismutase(SOD), catalase (CAT),
Glutathion peroxidase(GSH-Px); Another kind of is non-enzyme polyphenoils, comprise tocotrienol, glutathion,
Melatonin, alpha-lipoic acid.Simultaneously, this combination contains all required bioelements of cell normal growth.Below its embodiment is described.
From following detailed, above-mentioned and other characteristics of the present disclosure will become more obvious.
This cell optimum organization thing contains 0.01-50% weight, the polyphenoils and the biologic trace element of preferred 2-20% weight.Preferably
Superoxide dismutase(SOD), catalase (CAT),
Glutathion peroxidase(GSH-Px), glutathion,
MelatoninBe selected from United States Biological (P.O. Box 261 Swampscott, MA; ) tocotrienol, the preferred Glanbia Nutritionals of alpha-lipoic acid (NA), and Inc. (2840 Loker Avenue East, Carlsbad, CA); The preferred CellTech Labs Inc. of bioelement (magnanimity/trace element), (PO Box 102,300 Continental Blvd, El Segundo, CA).
The alternate manner of embodiment of the present invention comprises and comprises said cell optimum organization thing, the acceptable pharmacy auxiliary agent of preparation and medicine, diluent and/or carrier.When with said cell optimum organization thing, pharmaceutical composition, preparation and medicament administration, expect that it contains the cell optimum organization material and the analog thereof of effective dose.
Pharmaceutical composition of the present invention, preparation and medicament orally-ingestible or parenteral.As the instance of oral administration form, can use pill, granula subtilis, coated pill, powder medicine, granule, capsule, microcapsule, syrup etc.As the instance of drug administration by injection form, can use injection (lyophilized preparation that comprises dissolving injection when being used to use) and suppository in addition.Again in addition, it can be made into Liposomal agents.
In addition; Pharmaceutical composition of the present invention, preparation and medicament can carry out administration for following form; For example solution, suspension, emulsion, microemulsion, topical agent, paste, plaster, ointment, coated pill, lotion, rectum capsule, drop, gel, spray, powder, aerosol, inhalant, transfusion solution or implantable drug delivery system wait existing known dosage form.
In pharmaceutical composition of the present invention, preparation and preparation of medicaments, can use pharmaceutical auxiliary agent and/or carrier (excipient).For example can use coloring agent, sweeting agent, flavoring agent, bonding agent, adsorbent, lubricant, disintegrating agent, softening agent, suspending agent, emulsifying agent, surfactant, stabilizing agent, pH regulator, dispersant, isotonic agent, ravine humectant, lytic agent, solubilizing agent, and/or absorption enhancer is as pharmaceutical auxiliary agent.These different forms can be by the preparation down of conventional method, aseptic condition.
In addition, in the form of said administration, according to service condition, the coating that functionalization can further be provided is enteric coating for example.Under situation, can use enteric coating and shell not to accomplish preparation with the solid form administration.In addition, such form of medication can discharge chemical compound with some part of drug release to intestinal with the mode that postpones.The representative example of for example suitable implant compositions is polymer body and wax.In addition, it can be in excipient places microcapsule.
The instance of said excipient is that crystalline fibers capital, saccharide (for example glucose, multitudinous sugar, lactose, D mannitol, D one sorbitol), starch (for example corn starch, potato starch, wheaten starch, rice starch), silicic acid steamed bun, phosphoric acid hydrogen are received, calcium hydrogen phosphate, twist rubber acid and receive and Pulvis Talci.
The instance of said disintegrating agent is the yellow natural gum of sodium carbonate, calcium carbonate, arabic gum, starch (for example corn starch, potato starch, wheaten starch, tapioca, rice starch), agar, alginic acid, silicate complex, limb, crystalline cellulose, lowly replace the notes propyl cellulose, the crosslinked methylcellulose of completing is received, completed methylcellulose calcium, completes methylcellulose and receive and complete methyl starch and receive.
The optional cellulose derivative of bonding agent of the present invention, starch, alginate, gelatin, polyvinyl adjoin coughs up a heatable brick bed reward, multitudinous sugar and Radix Acaciae senegalis.Wetting agent is glycerol, 16 a heatable brick bed bases alcohol, glycerol monostearate vinegar, stearic acid town, Pulvis Talci, calcium stearate, solid polyethylene glycol and 12 a heatable brick bed base sodium sulphates.
Absorption enhancer of the present invention is season to plate chemical compound and analog thereof.
Adsorbent of the present invention is Kaolin and Ban Tuo soil.
Lubricant of the present invention is that the sixth of the twelve Earthly Branches west palm wax, hydrogenated oil and fat, stearic acid steamed bun, calcium stearate, phosphoric acid hydrogen are received, calcium hydrogen phosphate and mortar Cera Flava.
Antiseptic of the present invention for to river rising in Ningxia and flowing into central Shaanxi yl benzoic acid vinegar, methaform, benzene is expected and sorbic acid.
Isotonic agent of the present invention is sugar and sodium chloride.Suspending agent is ethoxylation isooctadecanol, polyoxyethylene sorbitol and sorbitol vinegar, microcrystalline Cellulose, soil, Pulvis Talci and yellow watt glue take off in aluminium hydroxide, class partially.
The instance of lytic agent of the present invention is dilute hydrochloric acid, sodium hydroxid, sodium bicarbonate, angle Trionyx sinensis Wiegmann alkene, normal saline, injection solvent, glucose, propylene glycol, polysorbate vinegar and Polyethylene Glycol.
Solubilizing agent of the present invention is selected from L-arginine, α one cyclodextrin, a white cyclodextrin, D-sorbitol, gathers the intoxicated and D-mannitol of dimension.
The instance of said pharmaceutical auxiliary agent only is as explanation, and the known various pharmaceutical auxiliary agent of said technical field is as long as they provide desired effects then all can use.
The liquid dosage form that is used for said compositions, pharmaceutical composition, preparation, medicine and the medicament of oral administration comprises the acceptable emulsion of medicine, solution, suspension and syrup.For example usually through with the dissolving of the close close derivant of said H and analog thereof or be dispersed in and form solution in the mixture of carrier (for example distilled water, normal saline, aqueous dextrose, glycerol, ethanol), lytic agent and emulsifying agent (for example ethanol, isopropyl alcohol, ethylene vinegar, acetic acid ethyl ester, benzyl alcohol, benzoic acid Wei vinegar, propylene glycol, 1,3 one butanediol and dimethyl methyl look down glue), oils (for example Fructus Maydis oil, olive oil, glycerol and sorbitan fat vinegar oil) or above-mentioned substance or suspension prepares such dosage form.
The dosage form that can prepare the present composition, preparation, medicine and the medicament that are suitable for injecting through the sterile powder that uses the acceptable aqueous of physiology or non-aqueous sterile solution, dispersion liquid, suspension, emulsion, aseptic injectable solution and/or be recovered to dispersion liquid.The representative example of suitable aqueous or non-water carrier, dilute solution, solvent or solvent is distilled water, ethanol, polyhydric alcohol (for example propylene glycol, Polyethylene Glycol and glycerol), its suitable mixture, vegetable oil and such as the organic vinegar of injectable of oleic acid second vinegar.These aqueouss or nonaqueous carrier, dilute solution, solvent or solvent can comprise suitable salt, pH regulator agent etc. in normal saline.
The dosage form that is suitable for the The compounds of this invention of local application comprises ointment, powder, spray and inhalant.Said active component mixes with the medicine acceptable carrier under gnotobasis, and as needs it also can be mixed together with buffer agent or spray.
The method of the said dosage form of this preparation of compositions is that said technical field is known; And be described in for example Remington's Pharmaceutical Sciences (< < Remington materia medica>>) 18th ed., Mack Publishing Company, Easton; PA, 1990) in.
Pharmaceutical composition of the present invention, preparation and medicament can use any dosage form of the route of delivery that is suitable for expecting, and can the limit cross following approach and accomplish and send: in for example oral, percutaneous, Intradermal, the bronchus, in intranasal, intra-arterial, intravenous, intramuscular, subcutaneous, intraperitoneal, intravaginal, internal rectum, Sublingual, intracranial, epidural, the trachea and other part.The instance of preferred route of administration is an oral administration, and this is because it can regulate dosage according to the order of severity of target disease state, improves the quality of life of user.
Pharmaceutical composition of the present invention, preparation and medicament have excellent cell optimization function, and the inhibition cell injury of excellence and the effect of cell death are provided.Correspondingly, can be with said pharmaceutical composition of the present invention, preparation and medicament therapeutic agent or preventive as degenerative disease.
Particularly, can bring into play pigmentation, psychosis, dementia, parkinson disease, insomnia and nervous system disorder syndrome that the prevention or the suitable disease of therapeutic effect include but not limited to that following degenerative disease such as myocardial infarction, ischemic heart disease, heart failure, angina pectoris, arrhythmia, arteriosclerosis, liver lipid metabolic disorder, hyperlipidemia, vascular hypertension, arteriosclerosis, hat arteriosclerosis, thrombosis, Arteriosclerosis obliterans, angiopathy, peripheral blood vessel, cholestegnosis disease, hypercholesterolemia, limb damage, internal organs depletion, acute, chronic hepatitis, stomach stain are die young, duodenum is burst and swing, steep the wearing out of dieing young property colitis, digestive organs damage, gallbladder disease, diabetes, muscle weakness, edema, osteoarthritis, osteoporosis, rheumatism, liver failure, hepatic injury, ischemic hepatic injury, liver lipid metabolic disorder, gallbladder injury, the depletion of chronic kidney, prostate hyperplasia, chronic prostatitis, Chronic obstructive pulmonary disease, emphysema, internal organs transplanting injury, diabetes, nosotoxicosis, internal organs transplanting injury, cancer, ischemic damage and reperfusion damage, tissue, skin histology and infection disease, visual deterioration, hearing loss.
The proper dosage scheme can be confirmed based on the information that provides in technique known knowledge, this description experience relevant with the individual subject of being treated.Usually, for pharmaceutical composition of the present invention, preparation and medicament, preferably can obtaining effective result, and the concentration administration of dangerous or deleterious side effect can not appear.Contain cell optimum organization thing of the present invention; In the acute toxicity test of mice, rat; LD50=1000mg/more than the Kg, toxicity is low, even be the administration of 500 mg/Kg/day in the subacute toxicity test of on rat, carrying out in addition to the maximum; Do not note abnormalities yet, proved degenerative disease prophylactic treatment of the present invention safe with compositions from these results.
The effective dose of said pharmaceutical composition of the present invention, preparation and medicament possibly change according to multiple factor; Said factor comprises activity level, metabolism, acting duration, rate of discharge, the delivery form (dosage form) of each chemical compound; Also comprise administration time, age, body weight, conventional health status, sex, diet that treatment is individual, the order of severity of combination of medicament (drug interaction) and individual symptom during administration.Those of ordinary skills can confirm effective dose through known information and the present disclosure of considering said technical field usually.Can carry out administration (for example the dosage umber of every day is 1 part to 4 parts) every day with the dosage that is divided into many parts, but also single dose administration.In addition, can be with every day, weekly or every month served as that administration is accomplished on the basis.
In these boundaries, treat the amount of the open compositions of the present invention that administered formulation comprises, be the amount that can in being controlled object, effectively obtain required effect.If it is used as medicinal preparation for oral administration; Then the dosage of effective ingredient will be with patient's symptom, age and body weight change, still as an embodiment, for the adult of body weight 60 kg; Can be once or 2 times to 3 times or be divided into more parts and give 1mg to 1,000 mg is as dosage every day.In addition, if it is as injection, then the dosage of effective ingredient will be with patient's symptom, age and body weight change; But as an embodiment; For the adult of body weight 60kg, can be once or 2 times to 3 times or be divided into more parts and give 1mg to 1,000 mg is as dosage every day.
In addition; Giving through intravenous injection under the situation of medicament of the present invention; The total amount that makes the dissolved substance in injection of the present invention or the drop injection of the present invention be 1 g/kg/hour below speed to veins such as veins, its amount is 0.1-50cc for every l kg body weight of people.The solute quality of injection amount to the high concentration more than 20 % time, also can begin from the liquid of low concentration, little by little improve concentration and carry out administration.The dosage of preparation of the present invention and medicament is different because of type of preparation, medication, but common 1 time is perhaps divided several to carry out administration with 1 μ mg/kg body weight/day – 10 mg/kg body weight/day.In addition; Particularly be accompanied by that internal organs are transplanted, during the ischemia-reperfusion of severe during the operation of the operations such as vascular bypass operation of heart and anemia, hypotension, the heart of pipe stop, during the ischemia-reperfusion of the general of pouring into again, reoxidizing etc. afterwards such as anoxia; If administration pharmaceutical composition of the present invention, preparation and medicament with and derivative salt be 100 mg/more than kg body weight/day, can obtain better effect.
" treatment " or " treatment among the present invention, about degenerative disease, abnormality and syndromic " comprise the inhibition of at least a degenerative disease state (or development of degenerative disease state): or the alleviation of degenerative disease state (or decline of degenerative disease state).Be preferably the alleviation (or decline of degenerative disease state) of degenerative disease state.
In addition; Among this paper about degenerative disease, abnormality and syndromic " fat in advance " and " prevention " comprise prevention wherein some individuality the tendency that is absorbed in the degenerative disease state is arranged; But be not diagnosed as this disease, and this morbid state is about to the situation of appearance in said individuality.The correlative detail of definite preventions such as normal experiment that can be through said those skilled in the art, research.
The mode of embodiment of the present invention has below been described, but these be merely of the present invention for example, except above-mentioned given content, can also use various formation.For example, in the mode of said embodiment, explain to concentrate on as the purposes of cytoprotective with as the medical usage of therapeutic agent, but the intent of the present invention and do not lie in and limit its medical usage especially.The present invention is with a wide range of applications in advance, outside medical usage, also has for example diagnostic agent, test agent etc.Cell optimum organization thing of the present invention can also be applied to accurate medicine, immune tonic, functional food etc.
[definitions]
Used term " medicinal " component of this cell optimum organization be a kind of people of being applicable to and do not have an adverse side effect (, stimulate, and anaphylaxis) such as toxicity with reasonably be benefited/risk is than corresponding component.
Term used herein " safety and effective dose " is meant that the amount of component when use with mode of the present invention is enough to produce with rational benefited/risk and replys than corresponding desired treatment and do not have adverse side effect (such as toxicity; Stimulate, or anaphylaxis).Specific " safety with effectively amount " obviously; To change with following factor: like the particular state of treatment, patient's physiological status, the persistent period of treatment; The characteristic (if any) of complication treatment, and employed particular formulations.
Term " bioelement " is meant magnanimity that cell activities is essential and a kind of or whole element in the trace element.The compositions that term " cell optimum organization thing " refers in particular to antioxidant group and bioelement group in the present invention.
Some above-mentioned term can use repeatedly in a structural formula, and each term can have separate scope.Some above-mentioned term use capable of being combined, and in this case, that at first mentions is combined into the replacement combination in the combination of mentioning afterwards, replaces point (addition point) and is positioned on the decline that whole combination mentions.
In sum; The present invention provides the preventing/treating medicament combination of the degenerative disease that oxidative stress causes; Its through with as effective ingredient show that in vivo the antioxidant and the bioelement of free radical scavenging activity are main component efficiently, in preparation with stability, to organism few side effects, safety, effectively be its characteristic.
[embodiment]
Below enumerate embodiment, the present invention will be described for comparative example.Certainly, these embodiment are discrete instances, and the present invention is not limited to the following example.
A. the conventional preparation process of compositions
Embodiment 1: injection solution
The hydroxylating rate the is 86% hydroxylating bioelement group * * of hydroxylating polyphenoils group * and hydroxylating rate 87% (mole converts) of (mole converts) with weight ratio 2:8 uniform mixing mixture; After being dissolved in the pharmaceutical ringer's solution of 1000cc fully with the concentration of 5 ppm; Filter with the mattress that goes out except that the mattress filter with the injection manufacturing, make injection solution and optimize agent as used for intravenous injection cell of the present invention.
* hydroxylating polyphenoils group: superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GSH-Px), glutathion, melatonin, tocotrienol, alpha-lipoic acid
* hydroxylating bioelement group: bioelement (magnanimity/trace element)
Embodiment 2: the oral administration powder
With with the hydroxylating rate the be 86% hydroxylating bioelement group * * of hydroxylating polyphenoils group * and hydroxylating 87% (mole converts) of (mole converts) with weight ratio 2:8 uniform mixing mixture; Mix and complex that the cell that forms is optimized with the composition of 5 weight % of 95 weight % and dibenzo fluoranthene (C20H10); Dilute in mannitol with 1% weight concentration; Process the prevention of following degenerative disease and the per os of treatment usefulness and use powder, include but not limited to promptly that myocardial infarction, ischemic heart disease, heart failure, angina pectoris, arrhythmia, arteriosclerosis, liver lipid metabolic disorder, hyperlipidemia, vascular hypertension, arteriosclerosis, hat arteriosclerosis, thrombosis, Arteriosclerosis obliterans, angiopathy, peripheral blood vessel, cholestegnosis disease, hypercholesterolemia, limb damage, internal organs depletion, acute, chronic hepatitis, stomach stain are die young, routed pigmentation, psychosis, dementia, parkinson disease, insomnia and the nervous system disorder syndrome of swinging, steeping the wearing out of dieing young property colitis, digestive organs damage, gallbladder disease, diabetes, muscle weakness, edema, osteoarthritis, osteoporosis, rheumatism, liver failure, hepatic injury, ischemic hepatic injury, liver lipid metabolic disorder, gallbladder injury, the depletion of chronic kidney, prostate hyperplasia, chronic prostatitis, Chronic obstructive pulmonary disease, emphysema, internal organs transplanting injury, diabetes, nosotoxicosis, internal organs transplanting injury, cancer, ischemic damage and reperfusion damage, tissue, skin histology of duodenum and infection disease, visual deterioration, hearing loss.
B. estimate (effect test :) the effect of various degenerative disease preventing/treatings
The trial zone that use is made up of the foregoing description 1 injection solution medicine and the injection of check plot (Lactated Ringer'S Solution (Lactated Ringer's solution)) compare affirmation to medicine of the present invention with the effect of compositions through following experiment.
1) to the effect test of the depleted disease of internal organs.
Utilize rat hat arterial occlusion model to carry out 320 seconds whole body ischemias, open blood flow thereafter again.Before testing, begin to measure the free radical interdependence chemiluminescence the tip blood not with General Corporation's inhibition and generation luminous organ, the result shows that blood flow opens the back again and just have significant free radical to rise immediately.In advance at the injection drug of the embodiment 3 of rat hat artery occlusion intravenous administration 5mg/kg before 15 minutes as the trial zone; Equally only inject ringer's solution as check plot and trial zone; After blood flow is opened again; 1 week, every day inject commensurability of the present invention relevant disease medicament 1 time, 2 week the back dissect, obtain with 45 Ca autoradiography/image analyzers that heart, liver, kidney, limb are dirty, the necrocytosis index of gallbladder.The rat of check plot is confirmed the tardy cell death of a plurality of necrocytosiss in each internal organs behind ischemia, but can significantly prevent the necrosis of each cell in the rat of having injected injection drug of the present invention (1 group 12) affirmation.
2) to the depleted comparative effectiveness test of internal organs
Utilize rat hat arterial occlusion model to carry out 320 seconds whole body ischemias, open blood flow thereafter again.Before testing, begin to measure the free radical interdependence chemiluminescence the tip blood not with General Corporation's chemiluminescent vessel, the result shows that blood flow opens the back again and just have significant free radical to rise immediately.In advance rat hat artery occlusion before 15 minutes to the injection solution of the embodiment 1 of rat intravenous administration 5mg/kg as the trial zone, equally only inject Lactated Ringer'S Solution (Lactated Ringer's solution as check plot and trial zone.After blood flow is opened again, 1 week, every day inject commensurability of the present invention above-mentioned medicine 1 time and use compositions, the back dissections of 2 weeks obtain with 45 Ca autoradiography/image analyzers that heart, liver, kidney, family are dirty, the necrocytosis index of gallbladder.The rat of check plot is observed with 45 Ca autoradiography/image analyzers; Behind ischemia, occur the tardy cell death of a lot of necrocytosiss in each internal organs, but can significantly prevent the necrosis of each cell in the rat of having injected injection drug of the present invention (1 group 10) affirmation.
Clinical trial
Below clinical trial to above-mentioned compositions (embodiment 2: the anti-oxidation efficacy oral administration powder) is assessed. said composition provides with the form of sachet.
1. research design
This test is the random experiment in one 20 week. and the experimenter (80 men, 40 woman) who always has 120 health has participated in current research. and these experimenters must satisfy the following standard that comprises:
A.) non-smoker does not take vitamin, antioxidant or estrogenic agents, thyroxine or fat-reducing medicament;
B.) blood glucose, liver and renal function test are normal;
C.) participate in this research interior no acute illness the first half;
D.) experimental session must not change former daily life style, and must not change the consumption that daily vitamin enriches food;
E.) during the research, must not accept any extra immune tonic or medicine.
The participant takes a sachet embodiment 2 oral administration powder every day in the time in four weeks.This sachet compositions one after each meal every morning. control group A (12 experimenters) is only taken α one thioctic acid, and matched group B (12 experimenters) only takes glutathion, α one thioctic acid and tocotrienol with embodiment 2 oral agents equivalent.
The experimenter of participation research group is being similar with the experimenter in two contrast knobs aspect age, body weight index and the Fat Distribution when beginning one's study.Safety evaluation comprises negative interaction and sign of life evaluation, blood test, biochemical investigation, urinalysis and physical examination.These are estimated before the treatment beginning and accomplish at baseline, then estimating weekly and after accomplishing this research fortnight in the treatment phase.
The analysis of antioxidase
Enzymatic activity is confirmed in fresh red blood cell. behind centrifugal 2 milliliters of blood, erythrocyte dissolves in distilled water (final volume is 10 milliliters) with isosmotic solution flushing three times then.The activity of SOD, GSH PX is according to Floh é and Otting (Floh é L.; Otting F., Methods Enzymol. 105:93-104,105:114-121; 1984) confirm that the CAT activity is according to Regulatory antioxidant enzymes such as Pippenger; Methods in Molecular Biology; Free Radical and Antioxidant Protocols (D. Armstrong, Ed. vol108, pp 299-313, Humana Press, Totowa NJ, 1998) confirms.The result representes with enzyme unit/milligram hemoglobin.
TRAP (total free radical is captured the antioxidation parameter) analyzes
Total free radical is captured antioxidation parameter (TRAP) according to Free Radic.Biol.Med. 18:29 one 36,1995 such as Ghiselli) confirm.
The blood plasma hydroperoxides quantitatively
D-ROMs kit test method that the estimation of serum oxidability adopts DIACRONs.r.l to produce. transition metal formed the basic free radical of money (ability OH) through Fenton type catalytic reaction under this method existed based on hydroperoxides.The amount of the hydroxyl radical free radical that produces is directly proportional with the amount that is present in the peroxide in the blood plasma, and this free radical is by N, and after N-diethyl-to a benzene two xanthan molecules was captured, forming λ max was the chromogen of 505 nm.
2 statistical analysiss
All knots are adopted with meansigma methods soil standard deviation and are represented. and adopt Student t to check the comparison of statistics between organizing.< 0.05 thinks significantly the P value.
The result
Blood plasma antioxidant status and peroxide level
Take embodiment 2 oral administration powder and caused significantly the increasing of total antioxidation state (table 2) in 21 days.From the mensuration of blood plasma TRAP value and lipid peroxidation product, obtained supporting the evidence of this enhanced antioxidant status.In two matched groups, also found the rising of suitable TRAP value, these two groups only use the part in the composition components, and promptly control group A is used α one thioctic acid, and matched group B uses that α-fertility is expected, alpha-lipoic acid and glutathion.
The activity of antioxidase in the erythrocyte
In treatment group, take specific activity that compositions causes treating antioxidase GSHPX in latter stage (p < 0.0l) than the good remarkable increase of baseline (table 3).After having found also among the matched group B that the GSHPX activity has some components of similar increase (p < 0.01) 0 supplement composition or compositions, find that the SOD activity does not have significant change.The group of taking compositions is in that the CAT in research latter stage is active significantly descends with baseline (p < 0.05); Observed the active downward trend of CAT in two matched groups, but the difference of the value that before taking some compositions of compositions, records does not reach statistical significance yet.
Security feature
This combination treatment better tolerance, and the experimenter who participates in nobody the side effect experience is arranged. do not note abnormalities through hematology and biochemical test.
Table 2 blood plasma antioxidant status
* p<0.05
** p<0.0l
***?p<0.00l
Table 3
Activities of antioxidant enzymes
* p<0.05
** p<0.0l
***?p<0.00l
Discuss
The conclusion of the experimental result of above-mentioned discussion has confirmed that person in middle and old age's degenerative disease prophylactic treatment compositions of the present invention has excellent treatment effectiveness and free radical elimination activity; And treatment better tolerance; Be free from side effects, therefore the prophylactic treatment medicine of person in middle and old age's degenerative disease of wide scope can be provided; The most of degenerative disease that promptly oxidative stress is caused has the medicine of effective active.Result of the present invention points out this cell to optimize drug regimen forcefully really can influence old and feeble process.
The above is merely embodiments of the invention; Be not so limit claim of the present invention; Every equivalent structure or equivalent flow process conversion that utilizes description of the present invention to do; Or directly or indirectly be used in other relevant technical fields, all in like manner be included in the scope of patent protection of the present invention.
Claims (10)
1. a pharmaceutical composition is used to prevent or treat the degenerative disease that oxidative stress causes, it is characterized in that said pharmaceutical composition comprises: one or more effective bioelements, one or more antioxidants, one or more pharmaceutical carriers.
2. pharmaceutical composition according to claim 1 is characterized in that, said bioelement comprises one or more the mixing in its pharmaceutically useful salt, active fat, active metabolite and its derivant.
3. pharmaceutical composition according to claim 1 is characterized in that, said antioxidant comprises one or more the mixing in its pharmaceutically useful salt, active fat, active metabolite and the derivant thereof.
4. pharmaceutical composition according to claim 1; It is characterized in that the effective bioelement of wherein an amount of one or more is selected from hydrogen (H), carbon (C), nitrogen (N), oxygen (O), fluorine (F), sodium (Na), magnesium (Mg), silicon (Si), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), ferrum (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), bromine (BR), molybdenum (Mo), stannum (Sn) and iodine (I).
5. pharmaceutical composition according to claim 1 is characterized in that, one or more antioxidants of said effective dose comprise non-enzyme antioxidant.
6. pharmaceutical composition according to claim 5 is characterized in that, said non-enzyme antioxidant comprises tocotrienol, glutathion, melatonin and alpha-lipoic acid.
7. pharmaceutical composition according to claim 1 is characterized in that, one or more antioxidants of said effective dose comprise one or more antioxidases.
8. pharmaceutical composition according to claim 7 is characterized in that said antioxidase comprises superoxide dismutase, catalase and glutathion peroxidase.
9. pharmaceutical composition according to claim 1 is characterized in that, the mass percent that said polyphenoils and biologic trace element account for said pharmaceutical composition is 0.01-50 %.
10. pharmaceutical composition according to claim 1 is characterized in that, the mass percent that said polyphenoils and biologic trace element account for said pharmaceutical composition is 2-20%.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104208059A (en) * | 2014-09-05 | 2014-12-17 | 中国医学科学院北京协和医院 | Application of melatonin in preparation of medicine for preventing smoking induced vascular damage |
| CN111110826A (en) * | 2020-02-11 | 2020-05-08 | 上海市第十人民医院 | Medicine composition for preventing cancer by targeting mitochondria and application thereof |
| CN111529545A (en) * | 2020-05-07 | 2020-08-14 | 四川农业大学 | Composition for relieving degenerative neuropathy and application |
| CN114667137A (en) * | 2019-11-15 | 2022-06-24 | 氧化还原平衡有限责任公司 | Methods of managing oxidative stress to regulate redox balance, prevent oxidative stress-induced cell damage and death |
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2012
- 2012-03-24 CN CN2012100804189A patent/CN102600203A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104208059A (en) * | 2014-09-05 | 2014-12-17 | 中国医学科学院北京协和医院 | Application of melatonin in preparation of medicine for preventing smoking induced vascular damage |
| CN114667137A (en) * | 2019-11-15 | 2022-06-24 | 氧化还原平衡有限责任公司 | Methods of managing oxidative stress to regulate redox balance, prevent oxidative stress-induced cell damage and death |
| CN111110826A (en) * | 2020-02-11 | 2020-05-08 | 上海市第十人民医院 | Medicine composition for preventing cancer by targeting mitochondria and application thereof |
| CN111110826B (en) * | 2020-02-11 | 2021-04-16 | 上海市第十人民医院 | Medicine composition for preventing cancer by targeting mitochondria and application thereof |
| CN111529545A (en) * | 2020-05-07 | 2020-08-14 | 四川农业大学 | Composition for relieving degenerative neuropathy and application |
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