CN109303786A - A kind of composition of resist oxygen lack and its application - Google Patents
A kind of composition of resist oxygen lack and its application Download PDFInfo
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- CN109303786A CN109303786A CN201811422600.1A CN201811422600A CN109303786A CN 109303786 A CN109303786 A CN 109303786A CN 201811422600 A CN201811422600 A CN 201811422600A CN 109303786 A CN109303786 A CN 109303786A
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- Prior art keywords
- hydroxytyrosol
- rhodioside
- derivatives
- composition
- drug
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HUAUNKAZQWMVFY-UHFFFAOYSA-M sodium;oxocalcium;hydroxide Chemical compound [OH-].[Na+].[Ca]=O HUAUNKAZQWMVFY-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The present invention provides a kind of compositions of resist oxygen lack, including rhodioside and hydroxytyrosol or derivatives thereof, and wherein the mass ratio of hydroxytyrosol or derivatives thereof and rhodioside is 1:100-20:1.The present invention also provides purposes of the hydroxytyrosol or derivatives thereof in the drug or functional food of preparation prevention and/or treatment hypoxic conditions.Hydroxytyrosol or derivatives thereof shows significant Oxygen-deficient endurance with rhodioside combination, and its activity is better than the rhodioside or hydroxytyrosol of one-component, the two has synergistic effect, it can achieve better curative effect using less dosage, mitigate drug to the burden of patient, it can be used for preventing and/or treating illness caused by the various anaerobic environments such as altitude sickness, improve the hypoxic conditions such as headache, dizziness, nausea and vomiting, periphery oedema, improve the hypoxia endurance of body.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of composition of resist oxygen lack and its application.
Background technique
Altitude sickness is common in the people for arriving at plateau at initial stage, these people usually there is no a degree of altitude acclimatization.
Altitude sickness symptom has self limiting, under normal circumstances can be voluntarily after 2 to 3 days if symptom can rest in time after occurring
It disappears.But if continue to be engaged in oxygen consumption physical sport after there is altitude sickness, or climb up the High aititude that oxygen more lacks
Area, altitude sickness symptom can aggravate even to progress to plateau brain edema or plateau pneumochysis and life danger occur.
Influencing principal element whether altitude sickness occurs has height above sea level, climbs speed and private medical service.Body enters
Behind plateau, respiratory system, the circulatory system, blood oxygen carrying capacity, which become again, immediately occurred adjustment and acclimatization.In human body each system it
Between and, the reaction of generation also difference different to the sensitivity of High aititude exposure between everyone.At 3000 meters of height above sea level
To 4500 meters of hypo, altitude sickness disease incidence is about 25% to 84%.Common altitude sickness has following six kinds of classification: light-duty urgency
Property altitude sickness, plateau pneumochysis, altitude coma, altitude erythrocytosis, plateau heart disease, altitude blood pressure abnormity.
Body composition change is intrinsic response of the body to hypoxemia low pressure reaction under altitude environment, and altitude sickness is only low
One of oxygen environment under low pressure type, in other hypoxemia environment under low pressure, people can may also generate " altitude sickness " symptom,
If astronaut is in space, will also tend to face hypoxemia environment under low pressure.Hypoxemia environment under low pressure can upset human body metabolic balance, make one
The metabolism enhancing of body ingredient breakdown.It is previous the study found that certain indexs of human body component become into after hypobaric hypoxia environment
Change, such as fat, protein, lean body mass etc. will appear decline.As exposure duration extends, shadow of the low-oxygen environment to human body component
It rings and persistently exists.
Currently, the drug of treated altitude sickness mainly has in the market: Rhodiola rosea capsules, silent blue feeding piece difficult to understand, plateau peace etc..
Wherein, studying discovery rhodioside by many years makes around the reduction of infarct range and infarct of cerebral ischaemia rat
Cortical neuron damage mitigates, and can increase cerebral blood flow (CBF) and reduces cerebral vascular resistance, to improve cerebral anoxia tolerance.Together
When, rhodioside can also inhibit the hippocampal cell member of hydrogen peroxide-induced to damage, and have preventive and therapeutic effect to cerebral ischemia；It can make
The expression of APE/Ref-1 positive cell number is increased, and the DNA for influencing neuron is repaired, and has neuroprotection.
But up to the present, most medicine effect mechanism is not still very clear, and the specific aim of adaptability is limited.It develops newly
Bioactive molecule is filled up vacancy, is still had a very important significance.
Hydroxytyrosol is the effective component in olive.In early stage research, it is believed that being the oleuropein in olive oil
It plays a significant role, by deepening continuously the study found that the hydrolysate hydroxytyrosol of oleuropein is living with stronger physiology
Property.In the prior art it has been reported that hydroxytyrosol has multiple biological activities, such as anti-oxidant, anticancer, protection eyesight, enhancing are soft
Bone Defect Repari, reducing blood lipid, treatment prostatic disorders etc., but do not have also up to now perhydroxyl radical tyrosol have can prevent or treat it is scarce
The report of the bioactivity of oxygen symptom (such as altitude sickness).
Summary of the invention
Aiming at the problems existing in the prior art, on the one hand, the present invention provides a kind of compositions of resist oxygen lack, wherein
Composition includes rhodioside and hydroxytyrosol or derivatives thereof, the quality of hydroxytyrosol or derivatives thereof and rhodioside
Than for 1:100-20:1.
Further, hydroxytyrosol or derivatives thereof and the mass ratio of rhodioside are 1:50-10:1, preferably 1:30-6:
1, more preferable 2:5.Wherein, the optimum ratio of hydroxytyrosol or derivatives thereof and rhodioside be 1:50,1:25,1:20,1:10,
1:5、2:5、1:2、1:1、2:1、5:1、5:2、6:1、10:1。
Further, hydroxytyrosol derivatives are the salifie form of hydroxytyrosol ester, hydroxytyrosol ether or hydroxytyrosol.
Further, hydroxytyrosol ester includes the ester that hydroxytyrosol and inorganic acid or organic acid are formed, it is preferable that hydroxyl
Tyrosol acetic acid esters；Hydroxytyrosol ether includes hydroxytyrosol alkyl ether, hydroxytyrosol aryl ether and hydroxytyrosol glucosides；Hydroxytyrosol
Salifie form be selected from the alkali metal salt of hydroxytyrosol, alkali salt or the salt formed with nitrogenous organic base.
Wherein, hydroxytyrosol ester includes the acceptable ester of pharmacology that hydroxytyrosol and inorganic acid or organic acid are formed, excellent
Selection of land, inorganic acid be selected from sulfuric acid, phosphoric acid, carbonic acid, hydrochloric acid, organic acid be selected from formic acid, acetic acid, propionic acid, butyric acid, maleic acid, oxalic acid,
Methanesulfonic acid, succinic acid or fatty acid.Hydroxytyrosol ether includes hydroxytyrosol alkyl ether, hydroxytyrosol aryl ether and hydroxytyrosol sugar
Glycosides, it is preferable that alkyl ether is selected from methyl, ethyl, n-propyl, normal-butyl, n-hexyl, n-octyl, isopropyl or tert-butyl, aryl
Ether be selected from carbon atoms aromatic ether, be also possible to containing nitrogen-atoms, sulphur atom, oxygen atom heteroaryl cyclic ethers, hydroxytyrosol sugar
Glycosides can be hydroxytyrosol glucoside or hydroxytyrosol fructoside.Hydroxytyrosol pharmaceutically acceptable salt is selected from hydroxyl junket
The alkali metal salt (such as sodium salt, sylvite) of alcohol, alkali salt (such as calcium salt, magnesium salts, ammonium salt), the salt formed with nitrogenous organic base,
Wherein nitrogenous organic base includes but is not limited to trimethylamine, triethylamine, tri-n-butylamine, pyridine, N, accelerine, N- methyl piperazine
Pyridine, N-methylmorpholine, diethylamine, dicyclohexylamine, dibenzyl amine, N- benzyl-β-phenethyl amine, N, N '-dibenzyl-ethylenediamin,
Procaine (Procaine), amphetamine (Amphetamine).
Further, the administration route of the composition can be oral administration, sublingual administration, intramuscular injection, vein drop
Note, acupoint injection therapy, dermal application or cavity/canal drug administration, preferably sublingual administration, intravenous drip or acupoint injection therapy, it is more preferably sublingual
Administration.
Further, the dosage form of the composition is selected from solid dosage forms, liquid dosage form, semisolid dosage form or gas formulation；
Preferably, the solid dosage forms is selected from tablet, capsule, pulvis, pill, granule, sustained release preparation, and the liquid dosage form is selected from
Injection, the semisolid dosage form are selected from gelling agent, ointment, and the gas formulation is selected from aerosol, spray.
Further, the dosage form of the composition is selected from oral agents, injection or external preparation, preferably oral agents or injection
Agent, more preferably oral agents；It is further preferred that oral agents are selected from sublingual lozenge, buccal tablets, conventional tablet, capsule, granule, drop
Pill.Wherein, injection includes but is not limited to injection, powder-injection, and external preparation is percutaneous or is administered through mucous membrane (such as schneiderian membrane)
Dosage form, including but not limited to aerosol, film, patch.Wherein, composition is drug or functional food.
On the other hand, the present invention also provides a kind of hydroxytyrosols or derivatives thereof in preparation prevention and/or treatment anoxic
The drug of symptom or the purposes in functional food.
Further, the drug further includes rhodioside, the mass ratio of hydroxytyrosol or derivatives thereof and rhodioside
For 1:100-20:1, preferably 1:50-10:1, more preferable 1:30-6:1, more preferable 2:5.
Further, drug or functional food can be improved the survival time under hypoxic condition, or improve blood oxygen saturation, or treatment by
Acute and chronic altitude sickness caused by anoxic, such as headache, dizziness, nausea and vomiting, periphery oedema symptom.In a kind of embodiment
In, hypoxic conditions further include similar with altitude sickness symptom as caused by overexercise, high altitude operation, diving operation etc..
Further, hydroxytyrosol derivatives are the salifie form of hydroxytyrosol ester, hydroxytyrosol ether or hydroxytyrosol,
It is preferred that hydroxytyrosol ester includes the ester that hydroxytyrosol and inorganic acid or organic acid are formed, it is further preferred that hydroxytyrosol acetic acid esters.
Hydroxytyrosol ether includes hydroxytyrosol alkyl ether, hydroxytyrosol aryl ether and hydroxytyrosol glucosides.The salifie form of hydroxytyrosol
Alkali metal salt, alkali salt selected from hydroxytyrosol or the salt with nitrogenous organic base formation.
Further, drug or functional food can also be combined with other anti-anoxic medicines；Preferably, the anti anoxia
Drug includes but is not limited to ginsenoside, Chrysophanol, Polysaccharides from Rosa roxburghii, Siberian solomonseal rhizome polysaccharide, purslane, orientoside, acetazolamide, phenylpropyl alcohol
Amine, Propranolol, nifedipine, dexamethasone.
Optionally, above-mentioned composition further includes auxiliary material, and wherein auxiliary material is to prepare drug, functional food, special doctor food, function
Energy property feed or the acceptable auxiliary material of cosmetics, such as filler, carrier, emulsifier, excipient.Correspondingly, containing the group of auxiliary material
Close object dosage form, can be beverage, soup, dairy products, nutrition bar, smear, dietary supplement, food additives, functional food,
Feed addictive, functional feed or cosmetic additive agent.
Inventor's discovery when carrying out biological activity test, hydroxytyrosol show significant Oxygen-deficient endurance, this
It did not reported also in the prior art.It has also been found that, hydroxytyrosol is combined the resistance to of resulting composition with rhodioside at the same time
Hypoxia activity be better than one-component hydroxytyrosol or rhodioside, even if with hydroxytyrosol derivatives (such as hydroxytyrosol ester or
Hydroxytyrosol ether) substitution hydroxytyrosol, the Oxygen-deficient endurance of the composition will not be influenced.
On the other hand, drug of the composition provided by the invention in addition to being applied to preparation prevention and/or treatment hypoxic conditions
With food China and foreign countries, enhancing hypoxia endurance can be also used for, correspondingly, the composition can be used for enhancing hypoxic tolerance
In the drug or functional food of ability.
The invention has the benefit that
The present invention provides a kind of compositions with Oxygen-deficient endurance, can be used for preparing prevention and/or treatment air hunger
Shape, the food or drug for enhancing hypoxia endurance function.It is demonstrated experimentally that hydroxytyrosol or derivatives thereof is combined with rhodioside
Composition show significant Oxygen-deficient endurance, and its activity is better than rhodioside or hydroxytyrosol of one-component, says
Bright hydroxytyrosol and rhodioside have synergistic effect.Composition provided by the invention can be used less to medicament simultaneously
Amount, reaches more preferable or comparable curative effect, alleviates drug to the body burden of patient, can be used for preventing and/or treating plateau
Illness caused by the various anaerobic environments such as reaction improves the hypoxic conditions such as headache, dizziness, nausea and vomiting, periphery oedema, improves machine
The hypoxia endurance of body.
Specific embodiment
For the clearer general idea for illustrating the application, below by way of examples to overall plan of the invention
It is described in detail.In the following description, a large amount of concrete details are given in order to provide to the more thorough reason of the present invention
Solution.It will be apparent, however, to one skilled in the art that the present invention may not need one or more of these details and
It is carried out.In other examples, in order to avoid confusion with the present invention, for some technical characteristics well known in the art
It is not described.
If do not explained separately, in the description of the invention: hydroxytyrosol is provided by Pharmaceutical Sciences, Shandong Province, lot number:
20171110, purity is greater than 98%；Rhodioside and remaining auxiliary material are bought by commercial sources；The biology of pharmaceutical composition
ICR mouse needed for activity experiment pleases experimental animal breeding Co., Ltd by Jinan friend and provides.
Embodiment 1
It is a kind of for preventing and/or treating tablet made of the composition of hypoxic conditions, raw material components are as follows:
Hydroxytyrosol 5g, rhodioside 250g, microcrystalline cellulose 150g, 8% starch slurry 20g, sodium hydrogensulfite 0.1g.
Above-mentioned raw materials are crushed after mixing, cross 14 meshes, are pelletized, 2h is dried in vacuo at 45 DEG C, adds 4g talcum
Powder is uniformly mixed, and whole grain is tabletted.
Embodiment 2
It is a kind of for preventing and/or treating tablet made of the composition of hypoxic conditions, raw material components are as follows:
Hydroxytyrosol 10g, rhodioside 200g, microcrystalline cellulose 150g, 8% starch slurry 20g, sodium hydrogensulfite 0.1g.
Above-mentioned raw materials are crushed after mixing, cross 14 meshes, are pelletized, 2h is dried in vacuo at 45 DEG C, adds 4g talcum
Powder is uniformly mixed, and whole grain is tabletted.
Embodiment 3
It is a kind of for preventing and/or treating capsule made of the composition of hypoxic conditions, raw material components are as follows:
Hydroxytyrosol 40g, rhodioside 100g, starch 70g, microcrystalline cellulose 80g, 8% starch slurry 20g, bisulfite
Sodium 0.1g.
Above-mentioned raw materials are crushed after mixing, cross 14 meshes, are pelletized, 2h is dried in vacuo at 45 DEG C, adds 4g talcum
Powder is uniformly mixed, whole grain, is packed into capsule.
Embodiment 4
It is a kind of for preventing and/or treating capsule made of the composition of hypoxic conditions, raw material components are as follows:
Hydroxytyrosol 50g, rhodioside 50g, microcrystalline cellulose 150g, 8% starch slurry 20g, sodium hydrogensulfite 0.1g.
Above-mentioned raw materials are crushed after mixing, cross 14 meshes, are pelletized, 2h is dried in vacuo at 45 DEG C, adds 4g talcum
Powder is uniformly mixed, whole grain, is packed into capsule.
Embodiment 5
It is a kind of for preventing and/or treating tablet made of the composition of hypoxic conditions, raw material components are as follows:
Hydroxytyrosol 50g, rhodioside 10g, microcrystalline cellulose 140g, 8% starch slurry 10g, sodium hydrogensulfite 0.1g.
Above-mentioned raw materials are crushed after mixing, cross 14 meshes, are pelletized, 2h is dried in vacuo at 45 DEG C, adds 4g talcum
Powder is uniformly mixed, and whole grain is tabletted.
Embodiment 6
It is a kind of for preventing and/or treating capsule made of the composition of hypoxic conditions, raw material components are as follows:
Hydroxytyrosol acetic acid esters 40g, rhodioside 100g, starch 70g, microcrystalline cellulose 80g, 8% starch slurry 20g are sub-
Sodium bisulfate 0.1g.
Above-mentioned raw materials are crushed after mixing, cross 14 meshes, are pelletized, 2h is dried in vacuo at 45 DEG C, adds 4g talcum
Powder is uniformly mixed, whole grain, is packed into capsule.
Each obtained tablet (capsule) 1000 (grain) of above-described embodiment, it is proposed that taking dose be 2 times a day, a 1-2
Piece (grain).
Above-mentioned tablet or capsule, which are all made of, to be prepared the common process method of the dosage form and prepares, and specific process step is no longer
It repeats.
In order to better understand the present invention, below with oxygen deficit tolerance experiment, Grasping clubglass test and the swimming with a load attached to the body of mouse
The resist oxygen lack bioactivity to illustrate aforementioned pharmaceutical compositions is tested, proves that gained pharmaceutical composition has altitude sickness with this
There is significant control efficiency.
Unless otherwise specified, the biological activity test 1-3 of gained pharmaceutical composition is provided as precondition with following:
ICR mouse 90, weight 18-22g are taken, animal room temperature is controlled at 20 DEG C -25 DEG C, relative humidity 45%-55%, round the clock 12h/
12h freely takes the photograph water and diet.Experiment is equipped with 1 model control group (i.e. blank control), 1 positive controls (with rhodioside
For positive control drug) and 7 experimental groups, wherein experimental group 1 contains only the hydroxytyrosol of one-component, experimental group 2-7 difference
Corresponding embodiment 1-6, every group of 10 mouse.Each group is administered intragastric administration on mice according to setting dosage, wherein model control group
To distilled water, 1 time a day, continuous 30d, stomach-filling volume is 0.1mL/10g weight.
Test the experiment of 1 oxygen deficit tolerance
At the 30th day of administration, all mouse carried out preserved skin operation, removed head fur.It, will be electric in 1h after the last administration
Pole is fixed on the skin of head of mouse, then each group mouse is respectively put into the 250mL port grinding bottle for filling 5g soda lime (every
1, bottle), it seals, with local organization blood oxygen saturation analyzer record mouse in exposed hypoxia process mesencephalic tissue part
The dynamic changes of blood oxygen saturation stop observing the mouse survival time for dead indication with breathing.Hydroxytyrosol is to mouse
The influence of oxygen deficit tolerance time-to-live the results are shown in Table 1:
Influence (mean ± SD) of 1 hydroxytyrosol of table to the mouse oxygen deficit tolerance time-to-live
Note: compared with model control group, P < 0.01 * P < 0.05, * *.
As shown in Table 1, compared with model control group, the mouse oxygen deficit tolerance time-to-live of experimental group 1-7 has significantly
Property improve, illustrate that composition associated with hydroxytyrosol or hydroxytyrosol derivatives and rhodioside has the work of significant resist oxygen lack
Property.Compared with the rhodioside of positive controls, 1 unknown significance difference of experimental group is shown comparable with rhodioside
Time-to-live illustrates that hydroxytyrosol has the curative effect of the hypoxia-bearing capability and prophylactic treatment altitude sickness that improve body, and hydroxyl
The lower dosage of base tyrosol (12mg) both may be implemented and rhodioside high dose (50mg) comparable effect.
It is also known by table 1, compared with positive controls, the mouse oxygen deficit tolerance time-to-live of experimental group 2-7 is mentioned
Height, and the mouse oxygen deficit tolerance time-to-live that the smaller experimental group 3-5 of accumulated dose is administered all has and significantly improves, and illustrates hydroxyl
Tyrosol and rhodioside combination have synergistic effect, and the Oxygen-deficient endurance that composition is shown is better than using the red of one-component
Red-spotted stonecrop glycosides or hydroxytyrosol.Wherein, experimental group 4 all has significant difference compared with other experimental groups, illustrates to work as pharmaceutical composition
When hydroxytyrosol and rhodioside ratio in object are 2:5, the Oxygen-deficient endurance of the pharmaceutical composition is best, and prevention and treatment plateau is anti-
The curative effect answered is best.
In addition, experimental group 7 has no notable difference compared to experimental group 4, illustrate to replace hydroxyl junket with hydroxytyrosol derivatives
Alcohol has no effect on curative effect as the component of composition.At the same time, the Oxygen-deficient endurance of each embodiment resulting composition is obviously excellent
In the hydroxytyrosol of one-component or the Oxygen-deficient endurance of rhodioside.
Compared with experimental group 1, the mouse oxygen deficit tolerance time-to-live of the identical experimental group 6 of administration accumulated dose has aobvious
It writes and improves, illustrate that hydroxytyrosol and rhodioside combination have synergistic effect, curative effect is used better than individual hydroxytyrosol.
Blood oxygen saturation is to account for all combinative hemoglobins by the capacity for the oxyhemoglobin that oxygen combines in blood
The percentage of capacity, i.e., the concentration of blood oxygen in blood, is the important physiological parameter of breath cycle, also directly reflects the life of body
Manage health status.The result of variations of blood oxygen saturation of each group mouse in port grinding bottle is shown in Table 2:
Blood oxygen saturation of the 2 each group mouse of table in port grinding bottle changes (mean ± SD)
Note: compared with model control group, P < 0.01 * P < 0.05, * *.
As shown in Table 2, compared with model control group, the blood oxygen saturation of the mouse of experimental group 1-7 in different time points is equal
It is improved, while mouse blood oxygen saturation extends 5min or more lower than the time of normal value, illustrates hydroxytyrosol and contains hydroxyl
The composition of base tyrosol or hydroxytyrosol derivatives has significant Oxygen-deficient endurance.Compared with positive controls, dosage
Lesser 1 unknown significance difference of experimental group, show with the comparable Oxygen-deficient endurance of rhodioside, illustrate hydroxytyrosol have
It is improved human body hypoxia-bearing capability and prevents and treats the curative effect of altitude sickness.
While and also it can be seen that, compared with positive controls, the blood oxygen saturation of the mouse of experimental group 2-7 in different time points
It is improved, mouse blood oxygen saturation is extended lower than the time of normal value, and the smaller experimental group 3-5 of accumulated dose is administered
Mouse blood oxygen saturation in different time points all have and significantly improve, illustrate that hydroxytyrosol and rhodioside combination have association
Same effect, and the hypoxia-bearing capability of composition is better than the rhodioside of one-component.Wherein, experimental group 4 and other experimental group phases
Than all having significant difference, illustrate when in pharmaceutical composition hydroxytyrosol and rhodioside ratio be 2:5 when, the medicine group
The Oxygen-deficient endurance for closing object is best, and the effect for preventing and treating altitude sickness is best.
In addition, experimental group 7 has no notable difference compared to experimental group 4, illustrate to replace hydroxyl junket with hydroxytyrosol derivatives
Alcohol has no effect on curative effect as the component of composition.At the same time, the Oxygen-deficient endurance of each embodiment resulting composition is obviously excellent
In the hydroxytyrosol of one-component or the Oxygen-deficient endurance of rhodioside.
Compared with experimental group 1, the blood oxygen saturation of the mouse of the identical experimental group 6 of administration accumulated dose in different time points
With significantly improving, illustrate that hydroxytyrosol and rhodioside combination have synergistic effect, curative effect makes better than individual hydroxytyrosol
With.
Test 2 Grasping clubglass tests
After last gives sample 2h, each group mouse is individually placed on perspex bar, mouse muscle is made to be in static(al)
Tense situation record time for being fallen from glass bar due to muscular fatigue of mouse, is terminated experiment when falling the 3rd time, added up 3 times
Time records data as the mouse pole-climbing time.The results are shown in Table 3:
Influence (mean ± SD) of 3 hydroxytyrosol of table to the mouse pole-climbing time
| Group | Dosage (/ day) | Number of animals (only) | The pole-climbing time (s) |
| Model control group | 0 | 10 | 1331±107 |
| Positive controls | 50mg rhodioside | 10 | 1556±99** |
| Experimental group 1 | 12mg hydroxytyrosol | 10 | 1552±103** |
| Experimental group 2 | 1mg hydroxytyrosol+50mg rhodioside | 10 | 1767±108** |
| Experimental group 3 | 2mg hydroxytyrosol+40mg rhodioside | 10 | 1988±112* |
| Experimental group 4 | 8mg hydroxytyrosol+20mg rhodioside | 10 | 2230±131** |
| Experimental group 5 | 10mg hydroxytyrosol+10mg rhodioside | 10 | 1999±97** |
| Experimental group 6 | 10mg hydroxytyrosol+2mg rhodioside | 10 | 1763±101* |
| Experimental group 7 | 8mg hydroxytyrosol acetic acid esters+20mg rhodioside | 10 | 2236±117** |
Note: compared with model control group, P < 0.01 * P < 0.05, * *.
As shown in Table 3, compared with model control group, there are conspicuousness raising, explanation in the mouse pole-climbing time of experimental group 1-7
Hydroxytyrosol and composition containing hydroxytyrosol or hydroxytyrosol derivatives cause anoxic equally to have significantly strong movements
Bioactivity.Compared with positive controls, the lesser 1 unknown significance difference of experimental group of dosage, show with it is red
The comparable Oxygen-deficient endurance of red-spotted stonecrop glycosides illustrates that hydroxytyrosol has the treatment for improving human body hypoxia-bearing capability and preventing and treating altitude sickness
Effect.
While and also it can be seen that, compared with positive controls, there is conspicuousness raising in the mouse pole-climbing time of experimental group 2-7,
The mouse pole-climbing time of the administration smaller experimental group 3-5 of accumulated dose, which all has, to be significantly improved, and illustrates hydroxytyrosol and rhodioside
Combination has synergistic effect, and the hypoxia-bearing capability of composition is better than the rhodioside of one-component.Wherein, experimental group 4 and its
For its experimental group compared to significant difference is all had, the hydroxytyrosol and rhodioside ratio for illustrating to work as in pharmaceutical composition are 2:5
When, the Oxygen-deficient endurance of the pharmaceutical composition is best, and the curative effect for preventing and treating altitude sickness is best.
In addition, experimental group 7 has no notable difference compared to experimental group 4, illustrate to replace hydroxyl junket with hydroxytyrosol derivatives
Alcohol has no effect on curative effect as the component of composition.At the same time, the Oxygen-deficient endurance of each embodiment resulting composition is obviously excellent
In the hydroxytyrosol of one-component or the Oxygen-deficient endurance of rhodioside.
Compared with experimental group 1, the mouse normal pole-climbing time of the identical experimental group 6 of administration accumulated dose, which has, to be significantly improved,
Illustrate that hydroxytyrosol and rhodioside combination have synergistic effect, curative effect is used better than individual hydroxytyrosol.
Test 3 swimming with a load attached to the body experiment
After last gives sample 2h, enable mouse weight bearing (the 5% of weight) (wherein, can be simultaneously in 30 ± 2 DEG C of water went swimmings
Use multiple 60cm × 40cm × 50cm sink, depth of water 30cm), being constantly gently agitated for the water surface makes mouse not stop to move about, with the second
Table records mouse from the swimming time for entering water and exhausting to tired power, and it is non-rising that mouse head enters water 7s, determines its swimming exercise extremely
Power exhausts, and record mouse since swimming start to death time.The results are shown in Table 4:
Influence (mean ± SD) of 4 hydroxytyrosol of table to the mice burden swimming time
Note: compared with model control group, P < 0.01 * P < 0.05, * *.
As shown in Table 4, compared with model control group, there is conspicuousness raising in the mice burden swimming time of experimental group 1-7,
Illustrate that hydroxytyrosol and the composition containing hydroxytyrosol or hydroxytyrosol derivatives have significant Oxygen-deficient endurance.With the positive
Control group is compared, and the lesser 1 unknown significance difference of experimental group of dosage is shown and the comparable resist oxygen lack of rhodioside
Activity illustrates that hydroxytyrosol has the curative effect for improving human body hypoxia-bearing capability and preventing and treating altitude sickness.
While and also it can be seen that, compared with positive controls, the mice burden swimming time of experimental group 2-7 has conspicuousness to mention
The mice burden swimming time of height, the administration smaller experimental group 3-5 of accumulated dose also all has and significantly improves, illustrate hydroxytyrosol with
Rhodioside combination has synergistic effect, and the hypoxia-bearing capability of composition is better than the rhodioside of one-component.Wherein, it tests
Group 4 all has significant difference compared with other experimental groups, illustrates when the hydroxytyrosol and rhodioside ratio in pharmaceutical composition
When example is 2:5, the Oxygen-deficient endurance of the pharmaceutical composition is best, and the Oxygen-deficient endurance of the pharmaceutical composition is best, and prevention and treatment is high
The curative effect of original reaction is best.
In addition, experimental group 7 has no notable difference compared to experimental group 4, illustrate to replace hydroxyl junket with hydroxytyrosol derivatives
Alcohol has no effect on curative effect as the component of composition.The Oxygen-deficient endurance of each embodiment resulting composition is substantially better than one-component
Hydroxytyrosol or rhodioside Oxygen-deficient endurance.
Compared with experimental group 1, mice burden swimming time of experimental group 6, which has, to be significantly improved, illustrate hydroxytyrosol with
Rhodioside combination has synergistic effect, and curative effect is used better than individual hydroxytyrosol.
In conclusion hydroxytyrosol shows the Substituted phenyl-lactic acid never reported in the prior art, can be applied to make
It is standby to prevent and/or the drug and food for the treatment of hypoxic conditions, meanwhile, provided as experiment basis containing hydroxytyrosol and
The pharmaceutical composition of rhodioside, Substituted phenyl-lactic acid are better than the hydroxytyrosol or rhodioside of one-component, have collaboration effect
It answers, the effect for preventing and treating altitude sickness is more preferable.Preferably, when hydroxytyrosol in pharmaceutical composition and rhodioside
Quality proportioning be 2:5 when, Oxygen-deficient endurance is best, and the curative effect for preventing and treating altitude sickness is best.
The above description is only an example of the present application, is not intended to limit this application.For those skilled in the art
For, various changes and changes are possible in this application.All any modifications made within the spirit and principles of the present application are equal
Replacement, improvement etc., should be included within the scope of the claims of this application.
Claims (10)
1. a kind of composition of resist oxygen lack, which is characterized in that the composition includes rhodioside and hydroxytyrosol or it spreads out
The mass ratio of biology, described hydroxytyrosol or derivatives thereof and rhodioside is 1:100-20:1.
2. composition according to claim 1, which is characterized in that described hydroxytyrosol or derivatives thereof and rhodioside
Mass ratio is 1:50-10:1, preferably 1:30-6:1, more preferable 2:5.
3. composition according to claim 1 or 2, which is characterized in that the hydroxytyrosol derivatives be hydroxytyrosol ester,
The salifie form of hydroxytyrosol ether or hydroxytyrosol；Preferably, the hydroxytyrosol ester includes hydroxytyrosol and inorganic acid or have
The ester that machine acid is formed, it is further preferred that hydroxytyrosol acetic acid esters；Preferably, the hydroxytyrosol ether includes hydroxytyrosol alkyl ether, hydroxyl
Base tyrosol aryl ether and hydroxytyrosol glucosides；Preferably, the salifie form of the hydroxytyrosol is selected from the alkali metal of hydroxytyrosol
Salt, alkali salt or the salt formed with nitrogenous organic base.
4. composition according to claim 1 to 3, which is characterized in that the administration route of the composition can be mouth
Clothes administration, sublingual administration, intramuscular injection, intravenous drip, acupoint injection therapy, dermal application or cavity/canal drug administration, preferably sublingual administration,
Intravenous drip or acupoint injection therapy, more preferably sublingual administration.
5. composition according to claim 1 to 4, which is characterized in that the dosage form of the composition is selected from solid formulation
Type, liquid dosage form, semisolid dosage form or gas formulation；Preferably, the solid dosage forms is selected from tablet, capsule, pulvis, ball
Agent, granule, sustained release preparation, the liquid dosage form are selected from injection, and the semisolid dosage form is selected from gelling agent, ointment, institute
It states gas formulation and is selected from aerosol, spray.
6. use of the hydroxytyrosol or derivatives thereof in the drug or functional food of preparation prevention and/or treatment hypoxic conditions
On the way.
7. purposes according to claim 6, which is characterized in that when anoxic survival can be improved in the drug or functional food
Between, or blood oxygen saturation is improved, or treatment acute and chronic altitude sickness as caused by anoxic.
8. purposes according to claim 6 or 7, which is characterized in that the drug or functional food further include root of kirilow rhodiola
Glycosides, the mass ratio of described hydroxytyrosol or derivatives thereof and rhodioside are 1:100-20:1, preferably 1:50-10:1, more preferably
1:30-6:1, more preferable 2:5.
9. according to purposes as claimed in claim 6 to 8, which is characterized in that the hydroxytyrosol derivatives are hydroxytyrosol
The salifie form of ester, hydroxytyrosol ether or hydroxytyrosol, it is preferable that the hydroxytyrosol ester includes hydroxytyrosol and inorganic acid or have
The ester that machine acid is formed, it is further preferred that hydroxytyrosol acetic acid esters；The hydroxytyrosol ether includes hydroxytyrosol alkyl ether, hydroxyl junket
Alcohol aryl ether and hydroxytyrosol glucosides；The salifie form of the hydroxytyrosol is selected from alkali metal salt, the alkaline-earth metal of hydroxytyrosol
Salt or the salt formed with nitrogenous organic base.
10. according to any purposes of claim 6-9, which is characterized in that the drug or functional food can also be with
The combination of other anti-anoxic medicines；Preferably, the anti-anoxic medicine include but is not limited to ginsenoside, Chrysophanol, Polysaccharides from Rosa roxburghii,
Siberian solomonseal rhizome polysaccharide, purslane, orientoside, acetazolamide, amphetamine, Propranolol, nifedipine, dexamethasone.
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