CN1694693A - Blood fluidity improving agent - Google Patents
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- CN1694693A CN1694693A CN 03824967 CN03824967A CN1694693A CN 1694693 A CN1694693 A CN 1694693A CN 03824967 CN03824967 CN 03824967 CN 03824967 A CN03824967 A CN 03824967A CN 1694693 A CN1694693 A CN 1694693A
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Abstract
A blood fluidity improving agent, a blood flow promoting agent and a cerebrovascular disorder ameliorating agent containing, as the active ingredient, at least one member selected from among chlorogenic acids, caffeic acid, ferulaic acid and pharmaceutically acceptable salts thereof. The above-described blood fluidity improving agent, blood flow promoting agent and cerebrovascular disorder ameliorating agent are highly safe and can be taken over a long period of time.
Description
Technical field
The present invention relates to a kind of blood fluidity improving agent, blood circulation accelerant and cerebrovascular disorders improving agent.
Background technology
Blood circulation and oxygen and nutrient are relevant to the excretory function of the supply of tissue and refuse, have important function.
In recent years, owing to the information equipment that with the computer is representative is got involved reasons such as living environment, keep the environment of same posture to increase for a long time, the people that each one of health produces poor circulation has also increased.And seasonal variations is also brought variation to vital movement, and for example, in the winter time, the situation of the poor circulation that causes circulating on every side etc. is a lot.And along with the increase at age, no one can avoid the reduction of physical function, all poor circulation might occur.
This poor circulation that causes because of a variety of causes such as living environment, seasonal variations or age increases many times will be to the smooth and easy obstacle that causes of health each several part vital movement, and the result causes body and mind unhealthy.
Existing blood circulation promotes composition or promotes that promoting as blood circulation that the composition of blood fluidity of key element is known has a collagen peptide (TOHKEMY 2002-121148 communique), the Bidens plant, particularly spend Herba Bidentis Bipinnatae and composition thereof (spy opens the 2002-205954 communique) in vain, gamma-Linolenic acid itself or gamma-Linolenic acid and fat-soluble antioxidant (spy opens the 2000-302677 communique), dilazep, its acid-addition salts (spy opens flat 11-92382 communique), hydroxymethylfurans formaldehyde derivatives (spy opens flat 11-228561 communique), estrogen effectual drug (spy opens flat 10-7564 communique), (spy opens flat 10-28567 communique) makes vinegar, Folium Mori, prunus mume (sieb.) sieb.et zucc. nuclear, plum pulp, materials such as Folium Perillae (spy opens flat 10-127253 communique), plasmin and plasminogen activator (spy opens flat 8-40931 communique), hyaluronic acid (spy opens flat 8-53356 communique), the bilobalide of one of Folium Ginkgo composition (spy opens flat 7-53371 communique) etc.
Apoplexy is a kind of of cerebrovascular disorders, is divided into cerebral infarction, cerebral hemorrhage etc.According to statistics, apoplexy death toll in Japan comes the 3rd after cancer, ischemic heart desease, and number of patients is very many.The risk factor of cerebrovascular disorders can be enumerated hypertension, diabetes, high fat of blood, from smoking, drink, the factor of living habit such as fat, life anxiety, along with the arriving of aging society from now on, the possibility of further increase is arranged.
At present; the active ingredient of prevention of brain angiopathy removes uses calcium antagonist; ACE hinders medicine; outside the pharmaceuticals such as α β blocade, also proposed to utilize glycerol lipid (spy opens the 2000-239168 communique) with the fatty acid residue that comprises two dodecahexaene acyl groups; MCP-1 (MonocyteChemotactic Protein-1) blocker (spy opens flat 11-60502 communique); chemical compound (spy opens flat 10-72363 communique) with anti-endothelin effect; chitosan (spy opens flat 10-182469 communique); activation of protein C (spy opens flat 7-233087 communique); the method of haptoglobin (spy opens flat 6-128173 communique) etc.
Summary of the invention
But in actual life, although the big multipotency of pharmaceuticals that is used to improve blood fluidity, blood circulation promoting or improve cerebrovascular disorders satisfies effectiveness, but, many products wherein are difficult to hemostasis on the other hand because of existing, night blood pressure drops too much, side effect such as hypotension, sky cough, have a headache, dizziness, patient's burden is big.And have the food that improves blood fluidity, blood circulation promoting or improve the cerebrovascular disorders effect or its active ingredient and neither one satisfy its effectiveness surely, and in most of the cases all need for a long time to showing the effect of improving blood fluidity, blood circulation promoting or improving cerebrovascular disorders.Therefore, the object of the present invention is to provide the effect height that a kind of blood flow property improvement, blood circulation promote or the cerebrovascular obstruction is improved, and safe, daily picked-up also can not bring blood fluidity improving agent, blood circulation accelerant and the cerebrovascular of burden to hinder improving agent.
For this reason, the inventor has blood flow property improvement effect for finding from the safe composition that can take for a long time or absorb, blood circulation facilitation effect and cerebrovascular hinder the composition that improves effect and carried out various researchs, found that: more than one that are selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt can be effectively as excellent blood fluidity improving agent, blood circulation accelerant and cerebrovascular disorders improving agent.But also find: when the people that the tip circulatory function is reduced takes more than one that are selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically-acceptable salts, improved the tip circulation, it is ice-cold to have improved trick, has also improved the body temperature reduction.Also find in addition: the side effect that material of the present invention does not almost have pharmaceuticals to assert is easy to picked-up, so can effectively be used as health food, pharmaceuticals etc. in the daily life.
That is, the invention provides a kind of more than one blood fluidity improving agents, blood circulation accelerant, the cold improving agent of body, body temperature reduction improving agent and cerebrovascular disorders improving agent as active ingredient to be selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
The present invention also provides more than one purposes in making blood fluidity improving agent, blood circulation accelerant, the cold improving agent of body, body temperature reduction improving agent and cerebrovascular disorders improving agent that are selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
The present invention also provides a kind of blood flow property improvement method, blood circulation promotion method, the cold improvement method of body, body temperature to reduce improvement method and cerebrovascular disorders improvement method, it is characterized in that that takes effective dose is selected from more than one of chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
Blood fluidity, blood circulation, body are cold because blood fluidity improving agent of the present invention, blood circulation accelerant etc. improve, body temperature reduces, so can be effective to increase etc. because of living environment, seasonal variations or age the prevention and the treatment of the whole blood poor circulation that produces.And cerebrovascular disorders improving agent of the present invention can be effective to the prevention and the treatment of cerebral infarction, cerebral hemorrhage, apoplexy.Since they safe, can be oral for a long time, so, not only can effectively be used as pharmaceuticals, and can also effectively be used as functional food, specific food for health care etc.
The specific embodiment
Used chlorogenic acid, caffeic acid, the ferulic acid of the present invention both can extract from the natural goods, the particularly plant that contain them, also can utilize the synthetic manufacturing of chemical industry.
There are stereoisomer in chlorogenic acid of the present invention, caffeic acid, ferulic acid, in the present invention, can use pure stereoisomer or its mixture.Chlorogenic acid of the present invention specifically comprises 3-caffeoyl guinic acid, 4-caffeoyl guinic acid, 5-caffeoyl guinic acid, 3,4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid, 4,5-dicaffeoyl quinic acid, 3-feruloyl quinic acid, 4-feruloyl quinic acid, 5-feruloyl quinic acid, 3-Resina Ferulae acyl-4-caffeoyl guinic acid etc. (people such as middle forest work " chemistry and technology that the coffee roasting is fried in shallow oil ", great learning are published Co., Ltd., 166～167 pages).
Make chlorogenic acid, caffeic acid, ferulic acid salify, can improve water solublity, improve physiologic effect.These salt so long as pharmaceutically acceptable salt get final product.The alkaline matter that forms this class salt and use can use for example alkali metal hydroxides such as Lithium hydrate, sodium hydroxide, potassium hydroxide; Alkaline earth metal hydroxide such as magnesium hydroxide, calcium hydroxide; Inorganic bases such as ammonium hydroxide; Basic amino acids such as arginine, lysine, histidine, ornithine; Organic bases such as monoethanolamine, diethanolamine, triethanolamine especially preferably use the hydroxide of alkali metal or alkaline-earth metal.In the present invention, modulate above-mentioned salt after, both can add in the compositions of forming by other composition, also can add to chlorogenic acid and salify composition in the said composition respectively and form salt therein.
Contain chlorogenic acid, caffeinic natural goods extract, particularly plant extract and for example be preferably extract from plant extract such as coffee, Brassica oleracea L.var.capitata L., Caulis et Folium Lactucae sativae, arithoke, Fructus Lycopersici esculenti, Fructus Solani melongenae, Rhizoma Solani tuber osi, Radix Dauci Sativae, Fructus Mali pumilae, pears, Fructus Pruni salicinae, peach, Fructus Pruni, Fructus Pruni pseudocerasi, Helianthi, Jew ' s marrow, Caulis Sacchari sinensis, Nan Tian's leaf, blue berry, Semen Tritici aestivis.
Chlorogenic acid is preferably the extract that extracts from plants such as raw coffee bean, Nan Tian's leaf, codlins.More preferably by Rubiaceae coffee (Coffee arabica LINNE) seed at the acid aqueous solution of Wen Shiyong ascorbic acid, citric acid or hot water extraction and extract.
Raw coffee bean extract specifically can be enumerated long paddy CHUANXIANG material (strain) " Flavor Folder "; Fructus Mali pumilae extract can be enumerated THE NIKKA DISTILLING CO., LTD. " Applephenon "; The sunflower seeds extract can be enumerated big Japanese ink chemical industry (strain) " Heliant " etc.
Contain the natural extract of ferulic acid, particularly plant extract and be preferably, be preferably the extract that from rice, extracts especially from for example coffee, Bulbus Allii Cepae, Radix Raphani, Fructus Citri Limoniae, Rhizoma Chuanxiong, Radix Angelicae Sinensis, pine, Rhizoma Coptidis, Resina Ferulae, Caulis Sacchari sinensis, corn, Fructus Hordei Vulgaris, Semen Tritici aestivi, rice etc.Rice of the present invention is meant living rice or its dry things such as rice section rice (Oryza sativa LINNE) kind.
The method of extracting ferulic acid from plant has for example following method: at room temperature, under weak basic condition, after the Testa oryzae oil that obtains by Testa oryzae with the preparation of aqueous alcohol and hexane, depress the ferulic acid ester that obtains by the aqueous alcohol component with hot sulphuric acid hydrolysis adding, make with extra care and obtain ferulic acid; Also can use contain by the alabastrum of Myrtaceae Flos Caryophylli wood (Syzygium aromaticum MERRILL etPERRY) and leaf vapor distillation and Oleum Caryophylli or by Oleum Caryophylli refining and the culture fluid culture of bacteria (Pseudomonas) of clove oil phenol, separate this culture fluid, the refining ferulic acid that obtains.
Ferulic acid also can be by the chemosynthesis manufactured such as condensation reaction (Journal of American Chemical Society, 74,5346,1952) of for example vanillin and malonic acid.
Above-mentioned composition of the present invention also can use two or more simultaneously.For reaching effects such as the effect of blood flow property improvement, blood circulation facilitation, these compositions are preferably adult (body weight 60kg) and absorb 10mg～10g, more preferably 35mg～5g, 70mg～1g more preferably every day.
The flow behavior of blood is the key factor in important circulation passive factor, the especially microcirculation.For example in blood capillary, the tiny arteriovenous, hemocyte mechanical characteristics such as erythrocyte abnormity energy, leukocyte adhesion energy are the hemorheological principal elements of domination, the inventor infers, the microcirculation disturbance that causes owing to the variation because of them constitutes the reason and the condition of illness of most of diseases.
Blood flow is improved the assay method of effect can enumerate microchannel method (Kikuchi, Y., Sato, K., Ohki H and Kaneko T.: " Optically accessible microchannels formed in a sngle-crystal silicon substrate for studies of blood rheology. " Microvasc.Res.44,226-240 (1992)), laser diffractometry (Manno S., Takakuwa Y., Nagao K., Mohandas N.,: " Modulation of erythrocyte membrane mechanical function by beta-spectrin phosphorylation and dephosphorylation. " J.Biol.Chem.270 (10), 5659-5665 (1995)), Filtration (Oonishi T., Sakashita K., Uyesaka N.: " Regulation of red blood cellfilterability by Ca
2+Influx and cAMP-mediated signaling pathways. " Am.J.Physiol.273 (6); C1828-1834 (1997)), micropipette method (DischerD.E.; Mohandas N.: " Kinematics of red cell aspiration by fluorescence-imaged microdeformation. " Biophys is (4) 1680-1694 (1996) J.71) etc.
Wherein, particularly the microchannel method is to use method the most widely.
It is 10 seconds～1000 seconds people by the time that the medication object of blood fluidity improving agent of the present invention is preferably whole blood.
The assay method of blood circulation facilitation effect can be enumerated laser doppler flowmetry (AbbotN.C., Ferrell W.R., Lockhart J.C., and Lowe J.G.: " Laser Doppler Perfusion imaging of skin blood flow using red and near-infrared sources. " J Invest Dermatol 107 882-886 (1996)); TOTM (HannaG.P., Fujise K., Kjellgren O., Feld S.Fife C., Schroth G., Clanton T., Anderson V., Smalling R.: " Infrapopliteal interventions for limb salvage in diabetic patients. " J.Am.Coll.Cardiol 30664-669 (1997)); Cold water immersion test (Kamimura.M., Comparision of alphatocopheryl nicotinate and acetate on skin microcirculation., Am.J.Clin.Nutr., 27,1110-1116 (1974)).Wherein, especially the cold water immersion test is the method that extensively adopts.
The medication object of blood circulation accelerant of the present invention is preferably for example in the cold water immersion test, cold water dipping (15 ℃, 5 minutes) hands or finger tip, the recovery time of the hands after removing or the skin temperature of finger tip (returning to 25 ℃ time), promptly be the people more than 10 minutes the recovery time of the finger table temperature behind the cold water load.
The angiopathy factor can be enumerated diabetes, hyperlipidemia, smoking, drink, fat and life anxiety etc., final blood vessel wall changes and roughly is divided into two kinds of medicated porridge shape arteriosclerosis and tiny arteriosclerosiss.Medicated porridge shape arteriosclerosis is the arteriosclerosis that causes because of the infiltration of the deposition of the breeding of the increase of tunica media and vascular smooth muscle cell, cholesterol and mononuclear cell-big phage etc.And the feature of tiny arteriosclerosis is degeneration necrosis, the hyalinization of the tunica media that occurs in littler blood vessel.This class angiopathy is a cerebrovascular disorders when resulting from brain circulation system, is one of life-threatening major disease.
Be that the cerebrovascular disorders of object improves that effect evaluation method is known a following method with the animal, promptly, apoplexy is easily sent out disease hypertension rat (SHRSP) (Yamori Y., Nagaoka A., Okamoto K.,: " Importance of genetic factors in hypertensive cerebrovascular lesion.:Ah evidence obtained by successive selective breeding ofstroke-prone and resistant SHR. " Jpn circ.J., 38,1095-1100 (1974)), mouse (Sasaki M., Laurence T.D., Teramoto A.,: collection is always made a copy of by " acute subdural hematoma type of mouse and ischemic pathological changes " Japanese neuro-surgery association, 59,273 (2000)), rabbit (rock paddy honor two, Yi Dongfangshi; the wild Yu of water is situated between, big wild happiness is bright for a long time, level land righteousness: " the low consumption nitroglycerin-Fasudic hydrochloride (hydrochloric acid Off ァ ス ジ Le) to rabbit subarachnoid hemorrhage type is also used therapy " cerebral vasospasm, 14,313-317 (1999)), Canis familiaris L. (bright time of island, river, the poor handsome Bamboo grass of paddy is former sincere, Jing Ze is just rich, the public friend in high storehouse, the island, palace is sincere: " to the effectiveness of the Pedis Canitis vasospasm type of salt brine slow releasing agent " cerebral vasospasm, 14,322-325 (1999)) etc.
In the present invention, estimated in the experiment of having used SHRSP effect to apoplexy.SHRSP be by hypertension natural occurrence rat (SHR) by assortative mating isolating inbred line.Because SHRSP produces hypertension along with the increase at age, cause cerebrovascular disorders, so be the typical animal of unique apoplexy natural occurrence, be extensive use of in the world.
The condition of illness of this SHRSP is extremely similar to the people on pathology, produces cerebral hemorrhage and cerebral infarction simultaneously.Common pathology is that arterionecrosis is basic pathological changes, just causes cerebral hemorrhage as long as break, and follows thrombosis generation cerebral infarction.
More than one results that improve blood fluidity that are selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt of the present invention are, promoted blood circulation, be that cold improving agent of effective body and body temperature reduce improving agent, and or effective cerebrovascular disorders improving agent.Their active ingredient in blood fluidity improving agent of the present invention, blood circulation accelerant and cerebrovascular disorders improving agent preferred add 0.01～80 weight %, more preferably 0.05～60 weight %, be preferably 0.1～60 weight % especially.
When blood fluidity improving agent of the present invention, blood circulation accelerant and cerebrovascular disorders improving agent are used as pharmaceuticals, pharmaceutically acceptable carrier can be added in the above-mentioned active ingredient, form oral or non-oral composition.
Orally administered composition can be enumerated tablet, granule, granula subtilis, pill, powder, capsule (comprising hard capsule and soft capsule), buccal tablet, chewable tablet, additive solid preparations such as (supplement) or powder formulation etc.And these preparations also can be used as food such as additive.
Consider effective intake of every day, the content of the composition of the present invention in these preparations is preferably 0.1～80 weight %, 10～60 weight % more preferably.
When blood fluidity improving agent of the present invention, blood circulation accelerant and cerebrovascular disorders improving agent are used as food, its food form can enumerate also that the beverage that added the common food additive outside the active ingredient, soy sauce, milk, yoghourt, beans etc. are liquid, emulsus or paste food except that above-mentioned preparation; Semi-solid such as fruit jelly, Fructus Elaeagni food; Forms such as cake, chewing gum, bean curd.
Consider effective intake of every day, the component content of the present invention in aqueous, emulsus or paste food or the semi-solid food is preferably 0.01～50 weight %, is preferably 0.05～10 weight % especially.
Non-oral composition can be enumerated intravenous injection, suppository, skin preparations for extenal use etc. such as injection.
Blood fluidity improving agent of the present invention, blood circulation accelerant and cerebrovascular disorders improving agent safe, bring any problem can for healthy people, subhealth state people, patient's diet, can tablet, the form of form, the particularly specific food for health care of additive form such as granule or the form of various beverages, various food uses.
Embodiment
Test example 1 (blood fluidity evaluation)
I) experiment material and method
(a) use animal
The apoplexy liability hypertension rat (SHRSP/Izm, male) in 6 weeks begins test after raising and train more than the week.Rat is all raised under the condition of 20～26 ℃ of temperature, humidity 40～70%, lighting hours 12 hours (morning 6 points～6 pm).
(b) medication administration method and dosage
Since 8 weeks, in 28 days, give embodiment, the dispensing of comparative example sample once a day, repeatedly.Medication administration method is oral, uses the replaceable injection tube of the polypropylene system that the oral probe of metallic is installed to force dispensing.Embodiment used chlorogenic acid (Sigma Chemical company) 50mg/kg/ days, and comparative example uses the pharmacy of water for injection (Da mound).The embodiment medium is a water for injection.
Feedstuff hives off from stocking up to, and the feedstuff that freely absorbs is solid feed CRF-1 (east yeast industry (strain)), and the feedstuff that freely absorb the back of hiving off is solid feed SP (feedstuff, the east yeast industry (strain) that contain 0.4% Sal).Hive off from stocking up to, the drinking water that freely absorbs is a tap water, and 1% saline solution is freely absorbed in the back of hiving off.
(c) test method
After finishing to offer medicine for sample repeatedly 28 days, take a blood sample and inject the VENOJECT II vacuum test tube 7 (Terumo company) of anticoagulant heparin 350 μ L (adding 5%) in advance with respect to whole blood.After the blood sampling, mix rapidly, as the blood measuring sample.Determinator uses cell microrheology determinator (MC-FAN: former raised path between farm fields Electronics Industry Company of Hitachi).Device has assembled the small stream array as the blood capillary model, under the certain pressure difference, measures the blood cell flow behavior.The blood capillary model uses the model that processes the small stream of 7 μ m on monocrystalline silicon substrate.
Measure at first is to measure under the 20cm water column pressure difference 100 μ L normal saline by the time (measured value is used for correction) of blood capillary model.Measure passing through the time (second) of 100 μ L blood measuring samples again.Per 10 μ L carry out one-shot measurement.With passing through of the blood capillary model of microscopic examination blood measuring sample.To be the blood fluidity index by the time, short more by the time, then judge can improve liquidity more.
Ii) result
As shown in Table 1, embodiment (chlorogenic acid dispensing group) compares with comparative example (water for injection dispensing group), by the time shortening, confirms that thus blood fluidity improves.
Table 1
| The blood throughput | By the time (second) | |
| ??μL | Embodiment | Comparative example |
| ??10 | ??4.87 | ??5.46 |
| ??20 | ??9.67 | ??10.59 |
| ??30 | ??14.31 | ??15.64 |
| ??40 | ??19.34 | ??20.73 |
| ??50 | ??24.59 | ??26.10 |
| ??60 | ??30.03 | ??32.24 |
| ??70 | ??35.90 | ??37.93 |
| ??80 | ??41.65 | ??43.70 |
| ??90 | ??47.58 | ??49.90 |
| ??100 | ??53.38 | ??56.34 |
Test example 2 (the tip circulatory function of cold water immersion test (Cooling-rewarming test) is estimated)
I) healthy women 5 people that allow the tip circulatory function reduce drink embodiment cooperation the beverage containing fruit or vegetable juice 125mL of raw coffee bean extract (being furnished with chlorogenic acid 140mg (0.1 weight %)), 1 bottle of every day, drank for 6 weeks.In the 3rd week after drinking for 6 weeks, allow identical person under inspection drink the beverage containing fruit or vegetable juice 125mL that does not contain raw coffee bean extract (being furnished with chlorogenic acid 6mg (0.005 weight %)) of comparative example, 1 bottle of every day, drank for 6 weeks.Estimate this person under inspection's tip circulatory function with the cold water immersion test.Test makes the person under inspection be accustomed to 20 ℃ of (50RH%) water after 30 minutes, left hand is dipped into 15 ℃ cold water and was dipped into wrist 5 minutes, measures and takes out the recovery temperature (Anritsu HPD-2236 DIGITALTHERMOMETER) that left hand the 3rd finger minor details in back refer to belly skin temperature.
Ii) result
The gained result is as shown in table 2.And table 2 has been represented to drink preceding and has been drunk recovery temperature behind after 6 weeks 45 minutes.As shown in table 2, one group of body temperature of embodiment effectively rises, and hence one can see that: improved the tip circulatory function by taking chlorogenic acid, promptly improved blood circulation.And, also reached and improved the effect that the body cold-peace is improved the body temperature reduction because of blood circulation improves.
Table 2: the recovery temperature of cold water immersion test (skin temperatures after 45 minutes)
| Before beginning to drink | After 6 weeks | |
| Embodiment | ??20.5±1.0 | ??22.8±2.0 * |
| Comparative example | ??21.7±1.3 | ??22.2±1.4 |
Meansigma methods ± standard deviation (n=5)
*: p＜0.05vs begins to drink preceding (Wilcoxon signed rank test)
The effect that 3 pairs of bodies of test example are cold, body temperature reduces symptom
I) experiment material and method
With 4 male is object, makes the tablet of being furnished with the 19mg ferulic acid (2 weight %) of embodiment, the tablet that does not add ferulic acid (0 weight %) of comparative example, estimates the variation that body is cold, body temperature reduces symptom.
Test is to absorb tablet after the degree of having estimated symptom in the morning, revalues the degree of symptom in afternoon.The symptom degree is estimated with following Pyatyi, and to improve achievement evaluation.
Achievement:
1 feels symptom
2 feel to have symptom slightly
3 can hardly be explained
How 4 do not feel symptom
5 do not feel symptom
Improve the achievement before the achievement-picked-up after achievement=picked-up
Ii) result
The cold result of table 3 expression body, the result that table 4 expression body temperature reduces.The present invention to arbitrary symptom to improve achievement all very high, confirm that above-mentioned symptom is all alleviated.
Table 3: body is cold
| Embodiment | Comparative example | |
| Before the picked-up | ??3.5 | ??3.5 |
| After the picked-up | ??4.3 | ??3.3 |
| Improve achievement | ??0.8 | ??-0.2 |
Table 4: body temperature reduces
| Embodiment | Comparative example | |
| Before the picked-up | ??3.5 | ??3.8 |
| After the picked-up | ??4 | ??3.5 |
| Improve achievement | ??0.5 | ??-0.3 |
Test example 4 cerebrovascular disorders improve Evaluation on effect
I) experiment material and method
(a) use animal
The apoplexy liability hypertension rat (SHRSP/Izm, male) in 6 weeks begins test after raising and train more than the week.Rat is all raised under the condition of 20～26 ℃ of temperature, humidity 40～70%, lighting hours 12 hours (morning 6 points～6 pm).
(b) medication administration method and dosage
Since 8 weeks, in 49 days, give embodiment, the dispensing of comparative example sample once a day, repeatedly.Medication administration method is oral, uses the replaceable injection tube of the polypropylene system that the oral probe of metallic is installed to force dispensing.Embodiment used chlorogenic acid (Sigma Chemical company) 50mg/kg/ days, and comparative example uses the pharmacy of water for injection (Da mound).The embodiment medium is a water for injection.
Feedstuff hives off from stocking up to, and the feedstuff that freely absorbs is solid feed CRF-1 (east yeast industry (strain)), and the feedstuff that freely absorb the back of hiving off is solid feed SP (feedstuff that contains 0.4% Sal), east yeast industry (strain)).Hive off from stocking up to, the drinking water that freely absorbs is a tap water, and 1% saline solution is freely absorbed in the back of hiving off.
(c) test method
Cause death for the animal blood-letting of surviving with pentobarbital, have or not apoplexy with histopathologic examination's investigation to final dispensing day.In addition, dead animal has or not apoplexy during the investigation dispensing at any time.
Ii) result
As shown in Table 5: embodiment (chlorogenic acid dispensing group) compares with comparative example (water for injection dispensing group), has obviously suppressed the apoplexy generation, confirms that thus having cerebrovascular disorders improves effect.
Table 5
| Use number of elements | Apoplexy is confirmed number | |
| Embodiment | ??10 | ??3 |
| Comparative example | ??10 | ??7 |
Example example 1 (soft capsule) (weight %)
Gelatin 70.0
Glycerol 22.9
Methyl parahydroxybenzoate 0.15
Propyl p-hydroxybenzoate 0.51
Water 6.44
With method commonly used soybean oil 400mg, caffeic acid 50mg and ferulic acid 50mg are filled in the soft capsule coating (ellipse, weight 150mg) of above-mentioned composition formation, make soft capsule.
Embodiment 2
The utilization example of representing beverage below.(weight %)
Defatted milk powder 3.5
Milk casein enzyme analyte 3.5
Fructose 9.0
Chlorogenic acid 0.3
Sodium ferulate 1.0
Citric acid 0.1
Ascorbic acid 0.1
Spice 0.1
Water 82.4
The storage stability height and the raciness of the beverage of above-mentioned composition.
Claims (24)
1. a blood fluidity improving agent is characterized in that, be selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt more than one as active ingredient.
2. blood fluidity improving agent as claimed in claim 1 is characterized in that, more than one the content that is selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt is 0.01～80 weight %.
3. a blood circulation accelerant is characterized in that, be selected from chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt more than one as active ingredient.
4. blood circulation accelerant as claimed in claim 2 is characterized in that, more than one the content that is selected from chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt is 0.01～80 weight %.
5. the cold improving agent of body is characterized in that, be selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt more than one as active ingredient.
6. a body temperature reduces improving agent, it is characterized in that, be selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt more than one as active ingredient.
7. a cerebrovascular disorders improving agent is characterized in that, be selected from chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt more than one as active ingredient.
8. cerebrovascular disorders improving agent as claimed in claim 7 is characterized in that, more than one the content that is selected from chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt is 0.01～80 weight %.
9. be selected from more than one purposes in the preparation blood fluidity improving agent of chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
10. purposes as claimed in claim 9 is characterized in that, more than one the content that is selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt is 0.01～80 weight %.
11. be selected from more than one purposes in the preparation blood circulation accelerant of chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt.
12. purposes as claimed in claim 11 is characterized in that, more than one the content that is selected from chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt is 0.01～80 weight %.
13. be selected from more than one purposes in the cold improving agent of preparation body of chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
14. be selected from more than one purposes in preparation body temperature reduction improving agent of chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
15. be selected from more than one purposes in preparation cerebrovascular disorders improving agent of chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt.
16. purposes as claimed in claim 15 is characterized in that, more than one the content that is selected from chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt is 0.01～80 weight %.
17. a blood flow property improvement method is characterized in that, that takes effective dose is selected from more than one of chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
18. blood flow property improvement method as claimed in claim 17 is characterized in that, more than one dosage every day that is selected from chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt is 10mg～10g.
19. a blood circulation promotion method is characterized in that, that takes effective dose is selected from more than one of chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt.
20. blood circulation promotion method as claimed in claim 19 is characterized in that, more than one dosage every day that is selected from chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt is 10mg～10g.
21. the cold improvement method of body is characterized in that, that takes effective dose is selected from more than one of chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
22. a body temperature reduces the improvement method, it is characterized in that, that takes effective dose is selected from more than one of chlorogenic acid, caffeic acid, ferulic acid or its pharmaceutically acceptable salt.
23. a cerebrovascular disorders improvement method is characterized in that, that takes effective dose is selected from more than one of chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt.
24. cerebrovascular disorders improvement method as claimed in claim 23 is characterized in that, more than one dosage every day that is selected from chlorogenic acid, caffeic acid or its pharmaceutically acceptable salt is 10mg～10g.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP322474/2002 | 2002-11-06 | ||
| JP2002322474A JP2004155700A (en) | 2002-11-06 | 2002-11-06 | Ameliorant for cerebrovascular disorder |
| JP323623/2002 | 2002-11-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1694693A true CN1694693A (en) | 2005-11-09 |
| CN100431537C CN100431537C (en) | 2008-11-12 |
Family
ID=32802659
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB038249677A Expired - Fee Related CN100431537C (en) | 2002-11-06 | 2003-09-03 | Blood fluidity improving agent |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP2004155700A (en) |
| CN (1) | CN100431537C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103381151A (en) * | 2012-05-04 | 2013-11-06 | 天士力制药集团股份有限公司 | Application of caffeic acid to prepare antithrombotic medicaments |
| CN108686213A (en) * | 2018-07-11 | 2018-10-23 | 军事科学院军事医学研究院环境医学与作业医学研究所 | Application of the cold sensation channel agonist in promoting body cold acclimatization ability |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20070107006A (en) * | 2005-02-28 | 2007-11-06 | 카오카부시키가이샤 | Prophylactic antistress agent |
| JP5040114B2 (en) * | 2006-01-12 | 2012-10-03 | マックス株式会社 | Battery pack locking mechanism and power tool |
| JP4990534B2 (en) * | 2006-02-02 | 2012-08-01 | ポーラ化成工業株式会社 | Caffeoylquinic acid derivative and composition for suppressing plasminogen activator inhibitor comprising the same as an active ingredient |
| JP6684156B2 (en) * | 2016-06-03 | 2020-04-22 | 花王株式会社 | Baked goods |
| KR102075799B1 (en) * | 2018-08-17 | 2020-02-10 | 경상북도 청송군(농업기술센터장) | Pharmaceutical composition comprising the extract of an unripe apple as an effective component for prevention or treatment of thrombosis and health functional food comprising the same |
| JP2020169124A (en) * | 2019-04-01 | 2020-10-15 | 花王株式会社 | Hotflash improver |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002145767A (en) * | 2000-08-30 | 2002-05-22 | Eijiro Tagashira | Therapeutic agent for circulatory disease and healthy food |
| CN1293955A (en) * | 2000-10-27 | 2001-05-09 | 王建蓉 | Anti-infective, antipyretic and antalgic medicine able to treat ophthalmopathy |
-
2002
- 2002-11-06 JP JP2002322474A patent/JP2004155700A/en active Pending
-
2003
- 2003-09-03 CN CNB038249677A patent/CN100431537C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103381151A (en) * | 2012-05-04 | 2013-11-06 | 天士力制药集团股份有限公司 | Application of caffeic acid to prepare antithrombotic medicaments |
| CN108686213A (en) * | 2018-07-11 | 2018-10-23 | 军事科学院军事医学研究院环境医学与作业医学研究所 | Application of the cold sensation channel agonist in promoting body cold acclimatization ability |
| CN108686213B (en) * | 2018-07-11 | 2021-08-06 | 军事科学院军事医学研究院环境医学与作业医学研究所 | Application of cold sensory channel agonist in preparation of medicine for promoting cold habit taking capability of organism |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100431537C (en) | 2008-11-12 |
| JP2004155700A (en) | 2004-06-03 |
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