CN102145076A - Rehmannia and new use of extract of rehmannia - Google Patents
Rehmannia and new use of extract of rehmannia Download PDFInfo
- Publication number
- CN102145076A CN102145076A CN2011100292059A CN201110029205A CN102145076A CN 102145076 A CN102145076 A CN 102145076A CN 2011100292059 A CN2011100292059 A CN 2011100292059A CN 201110029205 A CN201110029205 A CN 201110029205A CN 102145076 A CN102145076 A CN 102145076A
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- ethanol
- radix rehmanniae
- disease
- liver
- extract
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Classifications
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- A—HUMAN NECESSITIES
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/80—Scrophulariaceae (Figwort family)
- A61K36/804—Rehmannia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/41—Crassulaceae (Stonecrop family)
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- A—HUMAN NECESSITIES
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
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- Medical Informatics (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
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Abstract
The invention provides a rehmannia and new use of the extract of the rehmannia, in particular to the use of the rehmannia or the extract of the rehmannia for preparing drugs or health products for improving the function of the liver and for preparing the drugs or the health products for treating and/or preventing the diseases and/or the illness relative to the liver. The result shows that the rehmannia or the extract thereof can effectively improve the functions of the liver of recovering the liver cells, improving the antioxidation capacity of the liver cells, reducing the content of the oxyradical (ROS) of the liver cell, and the like. Furthermore, the rehmannia or the extract of the rehmannia can be used for treating and/or preventing the diseases or the illness relative to the liver, such as liver damage, fatty liver, cirrhosis and liver failure.
Description
Technical field
The invention belongs to the medicines and health protection product technical field, be specifically related to the new purposes of Radix Rehmanniae and extract thereof.
Background technology
Radix Rehmanniae is the fresh or dried root of scrophulariaceae rehmannia glutinosa plant Rehmannia glutinosa Libosch.Excavate autumn, removes reed head, fibrous root and silt, using fresh herb; Or Radix Rehmanniae slowly cured to about eighty per cant do.The former practises title " Radix Rehmanniae ", and the latter practises title " Radix Rehmanniae "." Chinese pharmacopoeia has been recorded Radix Rehmanniae always and has been concocted the processed goods Radix Rehmanniae Preparata for many years.As seen its critical role in Chinese crude drug.
The clinical practice of Radix Rehmanniae is very extensive.In recent years, a lot of researchs have been carried out to chemical constituent and the pharmacological action of Radix Rehmanniae in the home and abroad.For its pharmacological action, it is reported that it can be used for immunity, endocrine, blood, cardiovascular and cerebrovascular vessel, nervous system etc.
Liver is human body maximum, most important detoxifcation internal organs, has powerful defence function of detoxification.Harmful substance enters liver and transforms by gastrointestinal tract, blood circulation, and therefore, liver also is subjected to the infringement of these toxicants easily, causes abnormal liver function, fatty liver, even continue to develop into liver cirrhosis, liver failure.For example, long-term or discontinuity heavy drinking can cause hepatic injury.Cause alcoholic hepatitis, fatty liver, until liver cirrhosis.
The health care of hepatic injury focuses on prevention, avoids contacting cause of disease poisonous substance as far as possible, effectively prevent and the protection approach for by antioxidation, slow down lipid peroxidation, protection hepatocyte structure.Clinical treatment for fatty liver at present is mainly the removal cause of disease, adjusts diet, uses strategies such as degrease medicine.
Therefore, this area still presses for and improves new method and the product that liver function is for example repaired hepatocyte, improved aspects such as hepatocyte oxidation resistance at present, and still need the new method and the product that treat and/or prevent disease relevant and/or disease, for example be used for the treatment of and/or prevent the new method and the product of aspects such as hepar damnification such as alcoholic liver injury and fatty liver, liver cirrhosis with liver.
Summary of the invention
The inventor studies by experiment and is surprised to find that, Radix Rehmanniae or its extract can be used for repairing hepatocyte, the oxidation resistance of enhance hepatocyte, the variation of control hepar damnification (as alcoholic liver injury) and fatty liver aspect.The above-mentioned effect of Radix Rehmanniae or its extract for example prevents and treats the effect of hepatic injury and fatty liver and does not see that as yet bibliographical information is arranged.The present invention is based on above-mentioned discovery and be accomplished.
The object of the present invention is to provide and to improve liver function and treat and/or prevent the disease relevant and/or the new method of disease with liver.
In a first aspect of the present invention, provide Radix Rehmanniae or its extract to be used for improving the purposes of the medicine or the health promoting product of liver function in preparation.
According to the purposes of first aspect present invention, the wherein said liver function that improves includes but not limited to repair hepatocyte, improves the hepatocyte oxidation resistance, reduces the content of oxyradical (ROS) in the hepatocyte etc.
In a second aspect of the present invention, provide Radix Rehmanniae or its extract disease and/or the medicine of disease or the purposes in the health promoting product in that preparation is used for the treatment of and/or prevention is relevant with liver.
According to the purposes of second aspect present invention, wherein said disease relevant with liver and/or disease include but not limited to disease and/or the disease relevant with liver that cause because of chemical substance (including but not limited to ethanol).Further, described disease relevant with liver and/or disease include but not limited to hepatic injury, fatty liver, hepatitis, liver cirrhosis, liver failure etc., the for example hepatic injury that causes because of factors such as ethanol, fatty liver, hepatitis, liver cirrhosis, liver failure etc., alcoholic fatty liver for example particularly, more particularly for example acute alcoholic fatty liver and chronic alcoholic fatty liver.
Third aspect present invention provides Radix Rehmanniae or its extract to be used for improving mammal (for example people) and relevant disease or the medicine of condition or the purposes of health promoting product of moving equilibrium imbalance in preparation.In one embodiment, provide Radix Rehmanniae or its extract to be used for improving mammal (for example people) and relevant disease or the medicine of condition or the purposes of health promoting product of moving equilibrium imbalance due to the chemical substance in preparation.In one embodiment, described chemical substance is an ethanol.In one embodiment, provide Radix Rehmanniae or its extract to be used for improving mammal (for example people) relevant disease or the medicine of condition or the purposes of health promoting product of back moving equilibrium imbalance of drinking in preparation.
Fourth aspect present invention provides Radix Rehmanniae or its extract to be used for improving mammal (for example people) disease or the condition relevant with anoxia or to be used for disease or the medicine of condition or the purposes of health promoting product anti-and stress be relevant in preparation.In one embodiment, provide Radix Rehmanniae or its extract to be used for improving mammal (for example people) disease or the condition relevant or to be used for disease or the medicine of condition or the purposes of health promoting product anti-and stress be relevant due to the chemical substance with anoxia due to the chemical substance in preparation.In one embodiment, described chemical substance is an ethanol.In one embodiment, provide Radix Rehmanniae or its extract to be used for improving mammal (for example people) tolerance anoxia relevant disease or condition or to be used for disease or the medicine of condition or the purposes of health promoting product anti-and stress be relevant in preparation.
Fifth aspect present invention provides Radix Rehmanniae or its extract to be used for improving the purposes of mammal (for example people) disease relevant with immunologic hypofunction or the medicine of condition or health promoting product in preparation.In one embodiment, provide Radix Rehmanniae or its extract to be used for improving mammal (for example people) disease relevant or the medicine of condition or the purposes of health promoting product with immunologic hypofunction due to the chemical substance in preparation.In one embodiment, described chemical substance is an ethanol.In one embodiment, provide Radix Rehmanniae or its extract to be used for improving mammal (for example people) back immunologic hypofunction relevant disease or the medicine of condition or the purposes of health promoting product of drinking in preparation.
Sixth aspect present invention provides Radix Rehmanniae or its extract to be used for improving mammal (for example people) disease or the condition relevant with injury of brain function or to be used to improve or improve the purposes of the medicine or the health promoting product of memory in preparation.In one embodiment, provide Radix Rehmanniae or its extract to be used for improving the low medicine of mammal (for example people) disease relevant or condition or memory or the purposes of health promoting product with injury of brain function due to the chemical substance in preparation.In one embodiment, described chemical substance is an ethanol.In one embodiment, provide Radix Rehmanniae or its extract to be used for improving mammal (for example people) low relevant disease or the medicine of condition or the purposes of health promoting product of back injury of brain function or memory of drinking in preparation.
Seventh aspect present invention provides Radix Rehmanniae or its extract to be used for the treatment of in preparation, prevention, and/or improve following disease, the medicine of disease or condition or the purposes in the health promoting product: the complete or damage of liver function (for example, repair hepatocyte, improve the hepatocyte oxidation resistance, reduce the content of oxyradical (ROS) in the hepatocyte), disease relevant with liver and/or disease are (for example, disease and/or the disease relevant that cause because of chemical substance (including but not limited to ethanol) with liver, hepatic injury, fatty liver, hepatitis, liver cirrhosis, liver failure, alcoholic fatty liver, acute alcoholic fatty liver, chronic alcoholic fatty liver), disease relevant with the moving equilibrium imbalance or condition are (for example due to chemical substance such as the ethanol, moving equilibrium imbalance after for example drinking), disease that anoxia is relevant or condition are (for example due to chemical substance such as the ethanol, anoxia after for example drinking), with disease that stress be relevant or condition (for example due to chemical substance such as the ethanol, due to after for example drinking stress), disease relevant with immunologic hypofunction or condition are (for example due to chemical substance such as the ethanol, immunologic hypofunction after for example drinking), disease relevant with injury of brain function or condition are (for example due to chemical substance such as the ethanol, injury of brain function after for example drinking), memory low (for example due to chemical substance such as the ethanol, the memory after for example drinking is low).In one embodiment, disease, disease or condition are relevant with chemical substance, promptly by due to the chemical substance.In further embodiment, described chemical substance is the mixture of ethanol or itself and water, for example drinks alcohol product.
According to each described purposes of first aspect present invention to the seven aspects, wherein said medicine or health promoting product can be used for especially people of mammal.
Each described purposes according to first aspect present invention to the seven aspects, wherein said medicine or health promoting product can be used for especially people of mammal, and this mammal especially people (particularly adult) uses the amount of this medicine or health promoting product to be equivalent to 3~30g Radix Rehmanniae every day, preferably be equivalent to 4~28g Radix Rehmanniae, more preferably be equivalent to 5~24g Radix Rehmanniae, more preferably be equivalent to 7~20g Radix Rehmanniae again, further preferably be equivalent to 9~15g Radix Rehmanniae.
According to each described purposes of first aspect present invention to the seven aspects, wherein said Radix Rehmanniae is selected from Radix Rehmanniae, Radix Rehmanniae and Radix Rehmanniae Preparata, preferred Radix Rehmanniae and Radix Rehmanniae Preparata.
Each described purposes according to first aspect present invention to the seven aspects, catalpol is 1: 1~1: 9 (w/w) with the content ratio of oligosaccharide in the wherein said Radix Rehmanniae extract, preferred 1: 1.2~1: 8, preferred 1: 1.5~1: 7, preferred 1: 2~1: 6, for example about 1: 2, about 1: 2.5, about 1: 3, about 1: 3.5, about 1: 4, about 1: 4.5, about 1: 5, about 1: 6.
Each described purposes according to first aspect present invention to the seven aspects, the content of catalpol is greater than 10% (percetage by weight in the wherein said Radix Rehmanniae extract, with the extract gross weight is that benchmark calculates), preferred 10~40%, preferred 10~35%, preferred 10~30%, preferred 10~250%, preferred 10~20%, for example about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%.
Each described purposes according to first aspect present invention to the seven aspects, the content of oligosaccharide is greater than 40% (percetage by weight in the wherein said Radix Rehmanniae extract, with the extract gross weight is that benchmark calculates), preferred 40~90%, preferred 40~85%, preferred 40~80%, preferred 40~75%, preferred 40~70%, preferred 40~65%, preferred 40~60%, for example about 40%, about 42%, about 44%, about 46%, about 48%, about 50%, about 52%, about 54%, about 56%, about 58%, about 60%.
Each described purposes according to first aspect present invention to the seven aspects, the content of catalpol is greater than 10% (percetage by weight in the wherein said Radix Rehmanniae extract, with the extract gross weight is that benchmark calculates), preferred 10~40%, preferred 10~35%, preferred 10~30%, preferred 10~250%, preferred 10~20%, for example about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%; And the content of oligosaccharide is greater than 40% (percetage by weight, with the extract gross weight is that benchmark calculates), preferred 40~90%, preferred 40~85%, preferred 40~80%, preferred 40~75%, preferred 40~70%, preferred 40~65%, preferred 40~60%, for example about 40%, about 42%, about 44%, about 46%, about 48%, about 50%, about 52%, about 54%, about 56%, about 58%, about 60%.
According to each described purposes of first aspect present invention to the seven aspects, also further contain other active substance in wherein said medicine or the health promoting product.In one embodiment, described other active substance is selected from Radix Achyranthis Bidentatae, Radix Rhodiolae or its combination.In one embodiment, contain Radix Rehmanniae, Radix Achyranthis Bidentatae and Radix Rhodiolae in described medicine or the health promoting product.In one embodiment, contain Radix Rehmanniae, Radix Achyranthis Bidentatae and Radix Rhodiolae in described medicine or the health promoting product, its weight proportion is 1: (0.1~1): (0.1~1) for example is 1: (0.1~0.5): (0.1~0.5), for example about 1: 0.25: 0.25.
According to each described purposes of first aspect present invention to the seven aspects, also randomly contain pharmaceutically acceptable carrier in wherein said medicine or the health promoting product.
According to each described purposes of first aspect present invention to the seven aspects, the Radix Rehmanniae in wherein said medicine or the health promoting product or other active substance (for example Radix Achyranthis Bidentatae, Radix Rhodiolae) can be crude drug or its extract (for example extract of water extract, alcohol extract or alcohol-aqueous mixtures).
According to each described purposes of first aspect present invention to the seven aspects, wherein said Radix Rehmanniae extract is to obtain by the method that comprises water extraction and ethanol precipitation; Perhaps, wherein said Radix Rehmanniae extract is Radix Rehmanniae medicated wine or ethanol extract.
Each described purposes according to first aspect present invention to the seven aspects, wherein said Radix Rehmanniae extract is prepared by a method comprising the following steps and obtains: Radix Rehmanniae is ground into fragment, use water extraction, with aqueous extract filtration, concentrating under reduced pressure, adding ethanol in concentrated solution precipitates, filter, with supernatant concentrating under reduced pressure and vacuum drying.
According to each described purposes of first aspect present invention to the seven aspects, wherein said Radix Rehmanniae extract obtains by comprising the steps:
A) Radix Rehmanniae (for example Radix Rehmanniae, Radix Rehmanniae or Radix Rehmanniae Preparata, preference such as Radix Rehmanniae) is pulverized into about 0.01~1cm
3(0.02~0.8cm for example
3, preference is as 0.05~0.5cm
3, preference is as 0.08~0.2cm
3, preference is as 0.08~0.15cm
3, preference such as 0.1cm
3) fragment, with water extraction 1~5 time (for example 1 time, 2 times, 3 times, 4 times, 5 times), add 2~10 times of amounts (for example about 2 times of amounts at every turn, about 3 times of amounts, about 4 times of amounts, about 5 times of amounts, about 6 times of amounts, about 7 times of amounts, about 8 times of amounts, about 10 times of amounts) water, soaked 0.5~10 hour (for example 0.5~8 hour, for example 1~6 hour, for example 2~4 hours, for example 2 hours, 3 hours, 4 hours) after, at 35~80 ℃ (for example 35~80 ℃, for example 40~70 ℃, for example 45~60 ℃, for example 45 ℃, 50 ℃, 55 ℃, 60 ℃) descended heating extraction 0.5~5 hour (for example 0.8~4 hour, for example 1~3 hour, for example 1 hour, 1.5 hour, 2 hours, 3 hours) [particularly for example stir down and extracted 1.5 hours] at 50 ℃;
B) merge each extracting solution, filter, be evaporated to every milliliter and contain and be equivalent to 0.5~3 gram (for example being equivalent to 0.5g, 1g, 1.5g, 2.5g) medical material;
C) above concentrated solution is added ethanol precipitation, make ethanol content reach 60%~90% (for example 65%~90%, for example 70%~85%, for example about 70%, about 75%, about 80%, about 85%), place, filter, the supernatant concentrating under reduced pressure, vacuum drying, promptly.
According to each described purposes of first aspect present invention to the seven aspects, wherein said Radix Rehmanniae extract is to obtain by the method that may further comprise the steps: Radix Rehmanniae is pulverized into about 0.1cm
3Fragment is used water extraction 2 times, adds 5 times of water gagings for the first time, soak after 2 hours, and heating extraction, 50 ℃ are stirred extraction 1.5 hours; Add for the second time 5 times of amounts of water, 50 ℃ are stirred extraction 1 hour; Merge extracted twice liquid, filter, be evaporated to every milliliter and contain 1 gram medical material, concentrated solution is added ethanol precipitation, make ethanol content reach 80%, placed 24 hours, filter, supernatant concentrating under reduced pressure vacuum drying promptly gets Radix Rehmanniae extract.
Each described purposes according to first aspect present invention to the seven aspects, wherein said medicine or health promoting product also can contain at least a other active component, and described other active component is selected from Chinese medicine, synthetic drug, mineral, natural product, extract.In one embodiment, described at least a other active component has the effect that Radix Rehmanniae or its extract is produced auxiliary, collaborative, potentiation etc.In one embodiment, described at least a other active component and Radix Rehmanniae or its extract have the relation of monarch.In one embodiment, described other active component is that those skilled in the art can select voluntarily based on existing knowledge (for example according to the Chinese prescription principle), and these selections help to make Radix Rehmanniae or its extract to bring into play the effect of the desired purposes of the present invention more fully.
Each described purposes according to first aspect present invention to the seven aspects, wherein said medicine or health promoting product can also be as the helper components of other medicines or health promoting product, perhaps as being applied to for example people's common component of animal jointly with these other medicines or health promoting product.
Eighth aspect present invention provides a kind of compositions (pharmaceutical composition for example, for example can be used as medicine or health promoting product), described compositions comprises improvement, treat and/or prevent the Radix Rehmanniae of effective dose or its extract and optional pharmaceutically acceptable carrier and other optional active substance.In one embodiment, described compositions is used for the treatment of, prevention, and/or improve following disease, disease or condition: the complete or damage of liver function (for example, repair hepatocyte, improve the hepatocyte oxidation resistance, reduce the content of oxyradical (ROS) in the hepatocyte), disease relevant with liver and/or disease are (for example, disease and/or the disease relevant that cause because of chemical substance (including but not limited to ethanol) with liver, hepatic injury, fatty liver, hepatitis, liver cirrhosis, liver failure, alcoholic fatty liver, acute alcoholic fatty liver, chronic alcoholic fatty liver), disease relevant with the moving equilibrium imbalance or condition are (for example due to chemical substance such as the ethanol, moving equilibrium imbalance after for example drinking), disease that anoxia is relevant or condition are (for example due to chemical substance such as the ethanol, anoxia after for example drinking), with disease that stress be relevant or condition (for example due to chemical substance such as the ethanol, due to after for example drinking stress), disease relevant with immunologic hypofunction or condition are (for example due to chemical substance such as the ethanol, immunologic hypofunction after for example drinking), disease relevant with injury of brain function or condition are (for example due to chemical substance such as the ethanol, injury of brain function after for example drinking), memory low (for example due to chemical substance such as the ethanol, the memory after for example drinking is low).In one embodiment, disease, disease or condition are relevant with chemical substance, promptly by due to the chemical substance.In further embodiment, described chemical substance is the mixture of ethanol or itself and water, for example drinks alcohol product.
According to the compositions of eighth aspect present invention, the wherein said liver function that improves includes but not limited to repair hepatocyte, improves the hepatocyte oxidation resistance, reduces the content of oxyradical (ROS) in the hepatocyte etc.
According to the compositions of eighth aspect present invention, wherein said disease relevant with liver and/or disease include but not limited to disease and/or the disease relevant with liver that cause because of chemical substance (including but not limited to ethanol).Further, described disease relevant with liver and/or disease include but not limited to hepatic injury, fatty liver, hepatitis, liver cirrhosis, liver failure etc., the for example hepatic injury that causes because of factors such as ethanol, fatty liver, hepatitis, liver cirrhosis, liver failure etc., alcoholic fatty liver for example particularly, more particularly for example acute alcoholic fatty liver and chronic alcoholic fatty liver.
According to the compositions of eighth aspect present invention, wherein said compositions can be used for especially people of mammal.
Compositions according to eighth aspect present invention, wherein said compositions can be used for especially people of mammal, and this mammal especially people (particularly adult) uses the amount of this medicine or health promoting product to be equivalent to 3~30g Radix Rehmanniae every day, preferably be equivalent to 4~28g Radix Rehmanniae, more preferably be equivalent to 5~24g Radix Rehmanniae, more preferably be equivalent to 7~20g Radix Rehmanniae again, further preferably be equivalent to 9~15g Radix Rehmanniae.
According to the compositions of eighth aspect present invention, wherein said Radix Rehmanniae and Radix Rehmanniae extract have any or the multinomial feature of first aspect present invention to the seven each described purposes of aspect.
According to the present invention, compositions of the present invention particularly pharmaceutical composition or its extract can be by oral or parenteral route administration.The dosage form that is suitable for oral administration has been said for example: tablet, capsule, solution, suspension, granule or pill etc.Be suitable for parenteral route such as vein, dosage form subcutaneous or intramuscular administration has been said injection for example.The use oral way uses compositions of the present invention or extract is preferred mode.
According to the compositions of eighth aspect present invention, it is the form of tablet, capsule, granule, pill or oral liquid.The preparation method of these dosage forms is well known to a person skilled in the art.
According to the present invention, the feature of each aspect wherein (if can not cause opposite with the present invention's spirit) is applicable to other either side of the present invention.
According to the present invention, the present composition particularly term described in the pharmaceutical composition " carrier " refers to pharmaceutical field pharmaceutical excipient or pharmaceutic adjuvant commonly used, as medical additive, and diluent or disintegrating agent etc.
Arbitrary specific embodiments according to either side of the present invention and each side, described term " medicine ", " extract ", " compositions ", " pharmaceutical composition ", " health promoting product " etc., not only can be referred to as a kind of have pharmacology and/or physiological function medicine, can also refer to have pharmacology and/or a physiological function product on behalf of a kind of, for example health-oriented products, for example functional food or health food.Therefore, the theme of various aspects is mentioned to term " medicine ", " extract ", " compositions ", " pharmaceutical composition ", " health promoting product " etc. according to the present invention, it will be understood by those skilled in the art that above-mentioned each term can represent that all desire meaning is used to improve liver function and includes but not limited to repair hepatocyte, improves the hepatocyte oxidation resistance, reduces the content of oxyradical (ROS) in the hepatocyte etc.; Can also represent that desire meaning is used for the treatment of and/or prevention is relevant with liver disease and/or disease for example include but not limited to the disease and/or the disease of being correlated with liver that causes because of chemical substance (including but not limited to ethanol), further, described disease relevant with liver and/or disease include but not limited to hepatic injury, fatty liver, hepatitis, liver cirrhosis, liver failure etc., the for example hepatic injury that causes because of factors such as ethanol, fatty liver, hepatitis, liver cirrhosis, liver failure etc., alcoholic fatty liver for example particularly, more particularly for example acute alcoholic fatty liver and chronic alcoholic fatty liver.
In the present invention, described experimenter is a vertebrates, and preferably mammal is more preferably the people.Arbitrary specific embodiments according to either side of the present invention and each side, described term " medical material ", " Chinese crude drug ", " Chinese medicine " etc., they can be a kind of natural origin (for example mineral or plant) materials, they are except can having the pharmacologically active effect as treatment, can also have the effect that is used to prevent, regulate physiological function, can also have the physiological action that other this paper does not enumerate certainly.According to arbitrary specific embodiments of either side of the present invention and each side, described term " treatment " and " prevention " usually are meant respectively at disease that produces symptom or the situation that do not produce symptom as yet carries out " treatment " and " prevention ".Each used term of the present invention has general sense understood by one of ordinary skill in the art.
Radix Rehmanniae of the present invention or its extract can improve liver function effectively, for example can repair hepatocyte effectively, improve the hepatocyte oxidation resistance, reduce the content of oxyradical (ROS) in the hepatocyte etc.In addition, the present invention finds, Radix Rehmanniae or its extract can be used for the treatment of effectively and/or prevention is relevant with liver disease and/or disease, disease and/or the disease relevant that causes because of chemical substance (including but not limited to ethanol) for example with liver, for example hepatic injury, fatty liver, hepatitis, liver cirrhosis, liver failure etc., the for example hepatic injury that causes because of factors such as ethanol, fatty liver, hepatitis, liver cirrhosis, liver failure etc., alcoholic fatty liver for example particularly, more particularly for example acute alcoholic fatty liver and chronic alcoholic fatty liver.
The specific embodiment
Further specify the present invention below by specific embodiment and experimental example.These embodiment and experimental example are only used for illustrating the present invention particularly more in detail, and it should be interpreted as and limit the present invention in any form.
Employed many materials and operational approach are well known in the art in the following examples and the experimental example, but to wherein being the necessary content of realization the object of the invention, the inventor still does detailed as far as possible description.Among below the embodiment and experimental example, as not specifying that used material and operational approach are well known in the art.
The mensuration of catalpol content in the Radix Rehmanniae extract
Can be quantitatively and the catalpol content in the qualitative determination Radix Rehmanniae extract of the present invention by following exemplary method.
Measure according to high performance liquid chromatography (Pharmacopoeia of People's Republic of China, version was an one in 2005, Chinese Pharmacopoeia Commission's volume, Chemical Industry Press's publication, appendix VI D).
Chromatographic condition and system suitability test: with the octadecylsilane bonded silica and be filler; With acetonitrile-0.1% phosphoric acid solution (1: 90) is mobile phase; The detection wavelength is 210nm.Number of theoretical plate calculates by the catalpol peak should be not less than 5000.
The preparation of reference substance solution: it is an amount of that precision takes by weighing the catalpol reference substance, adds mobile phase and make the solution that every 1ml contains 10 μ g, promptly.
The preparation of need testing solution: get extract, after 24 hours, grind to form fine powder through 80 ℃ of drying under reduced pressure, precision takes by weighing about 0.1g, puts in the 25ml measuring bottle, and adding methanol is an amount of, supersound process 2 hours, and methanol constant volume is used in cooling.Filter, get subsequent filtrate and dilute suitable multiple (catalpol content that for example is diluted to wherein is suitable with reference substance solution concentration) with mobile phase.
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, calculate the percent that catalpol accounts for extract weight, promptly.
One, embodiment
Embodiment 1: the preparation of ground bloom
The full medical material of Radix Rehmanniae (commercially available) is washed, vacuum drying, temperature is 60-90 ℃, pulverizes, and crosses 60 to 100 mesh sieves, promptly gets the full medical material powder of Radix Rehmanniae.This ground bloom is brown crystalloid powder, and is water-soluble, standby.
In the present embodiment, used Radix Rehmanniae medical material is selected Radix Rehmanniae, Radix Rehmanniae or Radix Rehmanniae Preparata for use.
Embodiment 2: the preparation of Radix Rehmanniae extract
Radix Rehmanniae is pulverized into about 0.1cm
3Fragment is used water extraction 2 times, adds 5 times of water gagings for the first time, soak after 2 hours, and heating extraction, 50 ℃ are stirred extraction 1.5 hours; Add for the second time 5 times of amounts of water, 50 ℃ are stirred extraction 1 hour; Merge extracted twice liquid, filter, be evaporated to every milliliter and contain 1 gram medical material, concentrated solution is added ethanol precipitation, make ethanol content reach 80%, placed 24 hours, filter, supernatant concentrating under reduced pressure vacuum drying promptly gets Radix Rehmanniae extract.
Measure catalpol content in the gained Radix Rehmanniae extract according to the qualitative and quantitative approach of catalpol in the above-mentioned Radix Rehmanniae extract, and according to well known to a person skilled in the art method, for example the oligosaccharide content in the chromatography determination gained Radix Rehmanniae extract.
As a result, the catalpol content of the extract that present embodiment obtains is greater than 10% (w/w), and oligosaccharide content is greater than 50% (w/w).
Embodiment 3: the preparation-medicated wine of Radix Rehmanniae extract or extractum (No. 1 side)
No. 1 square wine (rehmannia root wine) preparation: draw 17.7% alcoholic solution 20ml, add the ground bloom 0.4g that embodiment 1 obtains, get No. 1 square medicated wine, be rehmannia root wine 21.06ml.This medicated wine can short-term or long-term the placement after drink, perhaps can behind short-term or long-term dipping, concentrate, thick paste, as extract of the present invention.Above-mentioned medicated wine can be described as square wine in this article No. 1, and in the test, " No. 1 side " and " No. 1 square wine " except the latter prepared with ethanol, the two can be regarded as identical in main constituent hereinafter.
Embodiment 4: the preparation-powder of Radix Rehmanniae extract, medicated wine or extractum (No. 3 sides)
No. 3 square powder is formed (the prescription ratio is 4: 1: 1) by Radix Rehmanniae, Radix Achyranthis Bidentatae, Radix Rhodiolae, is provided by this chamber Chinese drug-treated group, is brown crystalloid powder, can be described as square powder in this article No. 3, its water soluble.Its consumption can be 0.4g/kg or 2g/kg in the animal experiment.No. 3 square wine preparations: draw 17.7% alcoholic solution 20ml, add square powder 0.4g No. 3, get No. 3 square medicated wine 21.06ml.This medicated wine can short-term or long-term the placement after drink, perhaps can behind short-term or long-term dipping, concentrate, thick paste, as extract of the present invention.Can be described as No. 3 square wine in this article or be called the side No. 3, in the test, " No. 3 sides " and " No. 3 square wine " except the latter prepared with ethanol, the two can be regarded as identical in main constituent hereinafter.
Embodiment 5: the capsule that comprises bloom or Radix Rehmanniae extract
Ground bloom or Radix Rehmanniae extract with embodiment 1 or 2 adds appropriate amount of starch respectively, mix homogeneously, encapsulated shell, obtain the capsule of ground bloom or Radix Rehmanniae extract, every seed lac wafer can be equivalent to Radix Rehmanniae 0.05g, 0.1g, 0.15g, 0.2g, 0.25g, 0.3g, 0.35g, 0.4g, 0.45g, 0.5g or 0.6g.
Embodiment 6: the tablet that comprises bloom or Radix Rehmanniae extract
Ground bloom or Radix Rehmanniae extract with embodiment 1 or 2 adds one or more an amount of convas tablet adjuvants (as starch respectively, dextrin, lactose, Icing Sugar, calcium sulfate, microcrystalline Cellulose, mannitol, magnesium stearate, gelatine size, mucialga of arabic gummy, methylcellulose, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl emthylcellulose, polyvidone, sodium alginate, Polyethylene Glycol, cross-linked carboxymethyl cellulose that, carboxymethyl starch sodium, Pulvis Talci, micropowder silica gel etc.) make tablet according to the conventional tablet preparation method.Every tablet of tablet can be equivalent to Radix Rehmanniae 0.05g, 0.1g, 0.15g, 0.2g, 0.25g, 0.3g, 0.35g, 0.4g, 0.45g, 0.5g or 0.6g.
Embodiment 7: the granule that comprises bloom or Radix Rehmanniae extract
Respectively ground bloom or one or more an amount of granule adjuvants commonly used (as dextrin, citric acid, sodium citrate etc.) of Radix Rehmanniae extract adding of embodiment 1 or 2 are made granule according to conventional granulates agent preparation method.The granule of per unit packing can be equivalent to Radix Rehmanniae 0.05g, 0.1g, 0.15g, 0.2g, 0.25g, 0.3g, 0.35g, 0.4g, 0.45g, 0.5g, 0.6g, 0.7g, 0.8g, 0.9g, 1.0g, 1.2g, 1.5g or 2.0g.
Two, experimental example
Experimental example 1: Radix Rehmanniae extract is to the protective effect of acute alcoholic fatty liver
The Radix Rehmanniae extract that the experiment medicine obtains for embodiment 2.
30 Balbc mices in good condition, 50% ethanol by the disposable gastric infusion of 4 gram/kg body weight, is divided into 6 groups: normal group at random; The I group is physiology saline control group; The II group is the Radix Rehmanniae extract (annotate: " 0.4 gram/kg body weight " is meant that the extract that the animal per kg body weight gives is equivalent to Radix Rehmanniae 0.4 gram, hereinafter also has similar meaning) of prevention group (irritated stomach in preceding 2 days in the ethanol administration and give Radix Rehmanniae extract) gastric infusion 0.4 gram/kg body weight; The Radix Rehmanniae extract of III group gastric infusion 0.5 gram/kg body weight; The Radix Rehmanniae extract of IV group gastric infusion 1 gram/kg body weight; The Radix Rehmanniae extract of V group gastric infusion 2 gram/kg body weight.After 16 hours, observe triglyceride variation in blood and the liver, and make pathology and detect.The result shows that the TG level obviously raises in the control group mice serum, and steatosis partly appears in hepatic tissue cell, a few cell necrosis.But Radix Rehmanniae extract treatment group mice TG value is all recovered (the results are shown in Table 1) to some extent, and downright bad hepatocyte obviously reduces, and the hepatic injury degree obviously alleviates.The prompting Radix Rehmanniae extract has protective action to the acute liver damage that ethanol causes.
Table 1, Radix Rehmanniae extract are to the protective effect of acute alcoholic fatty liver
Grouping | Triglyceride (TG) |
Normally | 1.204±0.2498088 |
The I group | 1.74±0.3695583 |
The II group | 1.17±0.3506644 |
The III group | 1.31±0.6069313 |
The IV group | 1.23±0.3906746 |
The V group | 1.27±0.4074051 |
Experimental example 2: Radix Rehmanniae extract is to the protective effect of chronic alcoholic fatty liver
The Radix Rehmanniae extract that the experiment medicine obtains for embodiment 2.
50 Wistar rats in good condition are divided into 4 groups at random, and the number of animals of I, II, III and IV group is respectively 10,12,14 and 14.The I group is the normal control group; The II group is model group, and promptly 50% ethanol was pressed the continuous gastric infusion of gram/kg body weight every days 2 60 days, set up chronic alcoholic liver injury model; III group is low dosage Radix Rehmanniae extract treatment group, promptly on the basis of modelling every day gastric infusion 0.5 gram/kilogram Radix Rehmanniae extract; IV group is high dose Radix Rehmanniae extract treatment group, promptly on the basis of modelling every day gastric infusion 1 gram/kilogram Radix Rehmanniae extract.Getting blood regulating liver-QI structure observation serum triglycerides and liver histopathology after 60 days changes.The result shows that the TG level obviously raises in the control group mice serum, the significant quantities of fat degeneration appears in hepatocyte, the a few cell necrosis, and follow the liver fibroblast proliferation, but Radix Rehmanniae extract treatment group mice TG value is all recovered (the results are shown in Table 2) to some extent, downright bad hepatocyte obviously reduces, and the hepatic injury degree obviously alleviates.The prompting Radix Rehmanniae extract has protective effect to the chronic hepatic injury that ethanol causes.
Table 2, Radix Rehmanniae extract are to the protective effect of chronic alcoholic fatty liver
Grouping | Triglyceride |
The I group | 0.77±0.17 |
The II group | 1.49±0.42 |
The III group | 1.02±0.15 |
The IV group | 0.95±0.05 |
Experimental example 3: No. 1 square wine of mouse stomach is to the influence of coordinated balance motion
1 test objective
By the runner assay device, make the animal passive activity, estimate mutual aid coordination, balance exercise, muscular strength and the neural influence of No. 1 square wine to animal.
2 test materials
2.1 trial target
Dehydrated alcohol, content 99.7%, density (20 ℃) is 0.789-0.791g/mL (meansigma methods is 0.790g/mL), lot number: 20090203, Chemical Reagent Co., Ltd., Sinopharm Group's product.
The rehmannia root wine that No. 1 square wine obtains for embodiment 3, its administration consumption is 0.4 gram/kg body weight.
2.2 laboratory animal
The KM mice, sex, female, the hero half and half of body weight, body weight 18-22g is provided by Military Medical Science Institute's Experimental Animal Center, and age in days 35-40 days, the laboratory animal quality certification was numbered moving word ScXK-(army) 2007-004 of doctor.
Animal feeding is in Military Medical Science Institute Experimental Animal Center mouse experiment chamber, and room temperature 22-24 ℃, about humidity 30%RH, illumination is good, regularly ventilates, and the zoopery condition quality certification is numbered SyXK (army) 2007-005.Animal is raised with Military Medical Science Institute's Experimental Animal Center and aims at piece material, ad lib and the drinking-water that mice produces.
3 test methods
3.1 runner experimental provision and experimental technique: runner diameter is that 3.5cm, length are 60cm, is partitioned into 5 equal partitions with the plastics plectane, cuts off 10cm at interval, at the uniform velocity rotates with 14 times/min by differential speed electromotor.Place 5 animals during each the experiment at most.
In this test, mouse gavaging alcoholic solution or rehmannia root wine, the administration volume is the 0.2ml/10g body weight, and 20min behind the medicine places mice on the transfer rod, and the number of animals of falling from transfer rod in the record 5min and every fall the animal drop-out time.
3.2 prerun: its purpose is sought the suitable ethanol dosage of a mouse gavaging, makes it rotate 5min on the runner experimental provision and falls 70-80% mice.Prerun the results are shown in Table 3-1.
Table 3-1. mouse gavaging different concentration ethanol is to the influence of coordinated balance motion
Annotate: ethanol density is calculated with 0.79g/ml; Administration volume 0.2ml/10g.b.w., wherein b.w. represents body weight.
Pre-test result shows: mouse gavaging 2.80 gram/kilogram ethanol have the ability of the animal disequilibrium coordination exercise about 80% approximately.So when formal experiment, adopt and gavage the alcoholic acid dosage of 2.80 gram/kilograms.
3.3 experiment grouping and medication: experiment is divided into normal control group, ethanol 2.8 gram/kilograms group (3.54ml/kg) and rehmannia root wine group (0.4 gram/kg body weight).Gavage in the 20min record 5min of back the number of animals of falling from transfer rod and fall the animal drop-out time.
3.4 alcoholic solution and No. 1 square wine preparing process
3.4.1 the preparation of alcoholic solution: formal test ethanol dosage is 2.80 gram/kilograms, during preparation 40ml alcoholic solution, draws dehydrated alcohol 7.08ml, adds distilled water to 40.00ml, and concentration of alcohol is 17.7%.Every mouse gavaging volume is 0.2ml/10g.b.w..
3.4.21 the preparation of number square wine: the method by embodiment 3 prepares.Every mice administration volume is 0.2ml/10g.b.w..
4 date processing
Experimental data is represented with mean ± standard deviation, with t check and X
2Mensuration is carried out significance test.
5 experimental results
Behind about 2 minutes of the mouse gavaging 2.80 gram/kilogram ethanol, be excited hyperfunction state, ataxic gait enters relative inhibitory state subsequently.No. 1 square wine of mouse gavaging, above-mentioned symptom alleviates to some extent.After gavaging 20 minutes, mice is put on the what transfer rod, at the uniform velocity rotate with 14 times/minute,, the results are shown in Table 3-2 to observe mice balance ability and drop-out time.
Table 3-2. mice (male and female half and half) gavages No. 1 influence that square wine moves to coordinated balance
Group | Dosage (g/kg) | Number of animals (only) | Fall thing number (only) | Drop-out time (second) |
Normal control | Drinking water | 20 | 0 | >300 |
Ethanol | 2.80 | 20 | 15 | 30.0±13.5 |
No. 1 square wine | Ethanol 2.80+ Radix Rehmanniae 0.4 | 20 | 6 | 73.0±42.8 ** |
Annotate:
*Compare with the ethanol group:
*P<0.01.
Experimental result shows, mouse gavaging ethanol or No. 1 square wine all can make the coordinated balance ability of animal reduce, improve significantly than gavaging the motion of ethanol mice coordinated balance merely but gavage No. 1 square wine mice, show mainly that animal falls that number of animals obviously reduces and the beginning drop-out time prolongs after obviously.Point out No. 1 side that the effect that improves coordinated balance moving equilibrium imbalance is after drinking arranged.
Experimental example 4: No. 3 square wine of mouse stomach are to the influence of coordinated balance motion
1 test objective
By the runner assay device, make the animal passive activity, estimate mutual aid coordination, balance exercise, muscular strength and the neural influence of No. 3 sides to animal.
2 test materials
2.1 trial target
2.1.1 dehydrated alcohol, content 99.7%, density (20 ℃) 0.789-0.791g/mL (meansigma methods is 0.790g/mL), lot number: 20090203, Chemical Reagent Co., Ltd., Sinopharm Group's product.
2.1.23 number square wine is prepared by embodiment 4, its consumption is 0.4 gram/kg body weight.
2.2 laboratory animal
The KM mice, sex, female, the hero half and half of body weight, body weight 18-22g, 20 every group, provide by Military Medical Science Institute's Experimental Animal Center, age in days 35-40 days, the laboratory animal quality certification was numbered moving word ScXK-(army) 2007-004 of doctor.
Animal feeding is in Military Medical Science Institute Experimental Animal Center mouse experiment chamber, and room temperature 22-24 ℃, about humidity 30%RH, illumination is good, regularly ventilates, and the zoopery condition quality certification is numbered SyXK (army) 2007-005.Animal is raised with Military Medical Science Institute's Experimental Animal Center and aims at piece material, ad lib and the drinking-water that mice produces.
3 test methods
3.1 runner experimental provision and experimental technique: runner diameter is that 3.5cm, length are 60cm, is partitioned into 5 equal partitions with the plastics plectane, cuts off 10cm at interval, at the uniform velocity rotates with 14 times/min by differential speed electromotor.Place 5 animals during each the experiment at most.
In this test, mouse gavaging alcoholic solution or No. 3 square wine, the administration volume is the 0.2ml/10g body weight, and 20min behind the medicine places mice on the transfer rod, and the number of animals of falling from transfer rod in the record 5min and every fall the animal drop-out time.
3.2 prerun: its purpose is sought the suitable ethanol dosage of a mouse gavaging, makes it rotate 5min on the runner experimental provision and falls 70-80% mice.Prerun the results are shown in Table 4-1.
Table 4-1 mouse gavaging different concentration ethanol is to the influence (prerun) of coordinated balance motion
Annotate: ethanol density is calculated with 0.79g/ml; The administration volume is 0.2ml/10g.b.w.;
Pre-test result shows that mouse gavaging 2.80 gram/kilogram ethanol have the ability of the animal disequilibrium coordination exercise of 70-80% approximately.So when formal experiment, adopt and gavage the alcoholic acid dosage of 2.80 gram/kilograms.Gavage back 20min, the number of animals of falling from transfer rod in the record 5min and fall the animal drop-out time.
3.3 experiment grouping and medication: experiment is divided into normal control group, ethanol 2.8 gram/kilograms group and No. 3 square wine groups.Gavage in the 20min record 5min of back the number of animals of falling from transfer rod and fall the animal drop-out time.
3.4 alcoholic solution and No. 3 square wine preparing process
1. the preparation of alcoholic solution: formal test ethanol dosage is 2.80 gram/kilograms (3.54ml/Kg), during preparation 40ml alcoholic solution, draws dehydrated alcohol 7.08ml, adds distilled water to 40.00ml, and concentration of alcohol is 17.7%.
2.3 the preparation of number square wine: according to No. 3 square wine of method preparation of embodiment 4.Every mice administration volume is 0.2ml/10g.b.w.
4 date processing
Experimental data is represented with mean ± standard deviation, with t check and X
2Mensuration is carried out significance test.
5 experimental results
Behind about 2 minutes of the mouse gavaging 2.80 gram/kilogram ethanol, be excited hyperfunction state, ataxic gait.No. 1 square wine of mouse gavaging, above-mentioned symptom alleviates to some extent.After gavaging 20 minutes, mice is put on the what transfer rod, at the uniform velocity rotate,, the results are shown in Table 4-2 to observe the mice balance ability with 14 times/min.
Table 4-2. mice (male and female half and half) gavages No. 3 influences that square wine moves to coordinated balance
Group | Dosage (g/kg) | Number of animals (only) | Fall thing number (only) | Drop-out time (second) |
Normal control | Drinking water | 20 | 0 | >300 |
Ethanol | 2.80 | 20 | 15 | 30.0±13.5 |
No. 3 square wine | Ethanol 2.80+3 number square powder 0.4 | 20 | 5 * | 78.3±34.7 *** |
Annotate:
*Compare with the ethanol group:
*P<0.05,
* *P<0.001.
The result shows that mouse gavaging ethanol or No. 3 square wine all can make the coordinated balance ability of animal reduce.Improve significantly than gavaging the motion of ethanol mice coordinated balance merely but gavage No. 3 square wine mices, show mainly that animal falls that number of animals obviously reduces and the beginning drop-out time prolongs after obviously.No. 3 square wine of different sexes mouse gavaging do not have notable difference to falling the number of animals minimizing and beginning drop-out time.Point out No. 3 sides that the effect that improves coordinated balance moving equilibrium imbalance is after drinking arranged.
Experimental example 5:1 number square wine causes the ataxic influence of mice balance coordination to ethanol
1 test objective:
By the runner assay device, make the animal passive activity, estimate No. 1 square wine ethanol is caused the ataxic influence of mice balance coordination.
2 test materials:
2.1 trial target
Dehydrated alcohol, content 99.7%, density (20 ℃) 0.789-0.791g/mL (meansigma methods is 0.790g/mL), lot number: 20090203, Chemical Reagent Co., Ltd., Sinopharm Group's product.
No. 1 square wine prepares according to the method for embodiment 3, and its consumption is 0.4 gram/kilogram or 2 gram/kilograms.Every mouse gavaging volume is 0.2ml/10g.b.w..
2.2 animal
The KM mice, sex, female, the hero half and half of body weight, body weight 18-22g is provided by Military Medical Science Institute's Experimental Animal Center, and age in days 40-45 days, the laboratory animal quality certification was numbered moving word ScXK-(army) 2007-004 of doctor.
Animal feeding is in Military Medical Science Institute Experimental Animal Center mouse experiment chamber, and room temperature 22-24 ℃, about humidity 30%RH, illumination is good, regularly ventilates, and the zoopery condition quality certification is numbered SyXK (army) 2007-005.Animal is raised with Military Medical Science Institute's Experimental Animal Center and aims at piece material, ad lib and the drinking-water that mice produces.
3 test methods
3.1 runner experimental provision and experimental technique: runner diameter is that 3.5cm, length are 60cm, is partitioned into 5 equal partitions with the plastics plectane, cuts off 10cm at interval, at the uniform velocity rotates with 14 times/min by differential speed electromotor.Place 5 animals during each the experiment at most.
3.2 observation index: (1). 20min behind the medicine places mice on the transfer rod number of animals of falling from transfer rod in the record 5min; (2). write down the time that every animal begins to fall.
3.3 prerun: its purpose is sought the suitable ethanol dosage of a mouse gavaging, makes it rotate 5min on the runner experimental provision and falls 70-80% mice.Prerun the results are shown in Table 5-1.Table 5-1 mouse gavaging different concentration ethanol is to the influence of coordinated balance motion
Annotate: 1. ethanol density is calculated with 0.79g/ml; 2. the administration volume is 0.2ml/10g.b.w.;
Pre-test result shows that mouse gavaging 2.80 gram/kilogram ethanol have the ability of the animal disequilibrium coordination exercise about 80% approximately.So when formal experiment, adopt and gavage the alcoholic acid dosage of 2.80 gram/kilograms.Gavage back 20min, the number of animals of falling from transfer rod in the record 5min and fall the animal drop-out time.
3.3. experiment grouping and medication: experiment is divided into normal control group, ethanol 2.8 gram/kilograms group and No. 1 square wine group.
3.4. the compound method of alcoholic solution and No. 1 square wine is with experimental example 3.
3.5. experiment grouping and medication: see Table 5-2
Table 5-2. experiment grouping and medication
Group | Dosage (g/kg) | Number of animals (only) | Medication |
Normal control | Drinking water | 10 | 1 time, behind the medicine 20 minutes, irritate stomach |
Ethanol | 2.8 | 10 | 1 time, behind the medicine 20 minutes, irritate stomach |
No. 1 square wine | Ethanol 2.8+1 number square powder 0.4 | 10 | 1 time, behind the medicine 20 minutes, irritate stomach |
4 date processing
Experimental data is represented with mean ± standard deviation, with t check and X
2Mensuration is carried out significance test.
5 experimental results
Behind about 2 minutes of the mouse gavaging 2.80 gram/kilogram ethanol, be excited hyperfunction state, ataxic gait.No. 1 square wine of mouse gavaging, above-mentioned symptom alleviates to some extent.After gavaging 20 minutes, mice is put on the what transfer rod, at the uniform velocity rotate,, the results are shown in Table 5-3 to observe the mice balance ability with 14 times/min.
No. 1 square wine of table 5-3. mouse gavaging is to the influence of coordinated balance motion
Group | Dosage (g/kg) | Number of animals (only) | Fall number of animals (only) | Beginning drop-out time (second) |
Normal control | Drinking water | 20 | 0 | >300 |
Ethanol | 2.8 | 20 | 14 | 30.0±14.5 |
No. 1 side | Ethanol 2.8+1 side 0.4 | 20 | 7 * | 73.0±42.8 ** |
Annotate:
*Compare with the ethanol group:
*P<0.05
* *P<0.001.
The result shows that mouse gavaging ethanol or No. 1 square wine all reduce the coordinated balance ability of animal.Improve significantly than gavaging the motion of ethanol mice coordinated balance merely but gavage No. 1 square wine mice, show mainly that animal falls that number reduces and the beginning drop-out time prolongs after obviously.Point out No. 1 side to have and improve the ataxic effect of coordinated balance after drinking.
Experimental example 6:1 number square wine causes the influence of mice anoxia enduring to ethanol
1. experiment purpose: anoxia is a kind of stressor, can cause that body produces various irritabilitys reactions, and this test objective is to observe No. 1 side ethanol is caused whether anoxia in mice has the improvement effect.
2. materials and methods:
2.1. tried trial target: dehydrated alcohol, with experimental example 3; No. 1 square wine is with experimental example 3.
2.2. laboratory animal: the KM mice, female, body weight 18-22g.
2.3. experimental technique: body weight is differed the mice random packet that is no more than 2g, after administration 30 minutes, respectively mice is put into the airtight wide mouthed bottle of volume identical (250ml), the sodica calx (10g) of equal quantities is housed, to absorb moisture and carbon dioxide in the bottle.Bottleneck is coated with all ± woods, bottleneck is sealed after putting into mice.Observe the mouse breathing dwell time with stopwatch.Calculate and respectively organize death time average ± standard deviation, make significance between t test comparable group.
2.4. experiment grouping and medication: see Table 6-1.
Table 6-1. experiment grouping and medication
Group | Dosage (g/kg) | Number of animals (only) | Medication |
Normal control | Drinking water | 10 | 1 time, behind the medicine 30 minutes, irritate stomach |
Ethanol | 2.8 | 10 | 1 time, behind the medicine 30 minutes, irritate stomach |
No. 1 square wine | Ethanol 2.8+1 number square powder 0.4 | 10 | 1 time, behind the medicine 30 minutes, irritate stomach |
3. experimental result: see Table 6-2
Show the influence of 6-2.1 number square wine to the mice anoxia enduring
Group | Dosage (g/kg) | Number of animals (only) | Hypoxia endurance time (branch) |
Normal control | Drinking water | 10 | 38.5±4.9 |
Ethanol | 2.8 | 10 | 36.8±5.0 |
No. 1 square wine | Ethanol 2.8+1 number square powder 0.4 | 10 | 43.9±6.9 * |
Annotate:
*Compare with the ethanol group:
*P<0.05
The result shows that behind the mouse gavaging 2.8 gram/kilogram ethanol, hypoxia endurance time decreases than normal control animal, and the mice hypoxia endurance time of taking No. 1 square wine is than ethanol group significant prolongation, significant difference (P<0.05).To show that No. 1 side is significantly increased the animal hypoxia-bearing capability, has anti-stress effect.
Experimental example 7:1 number square wine is to immunologic hypofunction mice due to the ethanol
The phagocytotic influence of mononuclear cell
Shape foreign bodies more commonly used, as colloidal-carbon, india ink, Chinese prepared Chinese ink,
51The veins such as mutant erythropoietin of Cr labelling are removed by the monokaryon phagocyte rapidly after injecting mice or rabbit blood circulation, are mainly settled down in the macrophage of liver and spleen.If the foreign body amount is constant, the speed of then eliminating from blood flow can reflect the phagocytic function of mononuclear phagocyte.
1. experiment purpose: observe No. 1 square wine to the cytophagic influence of immunologic hypofunction mouse monokaryon due to the ethanol.
2. materials and methods
2 test materials:
2.1 trial target: dehydrated alcohol, with experimental example 3; No. 1 square wine is with experimental example 3.
2.2. reagent india ink (black ink) is commercially available, Beijing chemical reagents corporation product.Lot number: 0070920.
2.3. laboratory animal: the same, the KM mice, male, body weight 18-22g.
2.4. immunologic hypofunction Preparation of model mouse gavaging concentration is 17.7% ethanol, gavaging volume is 0.2ml/10g.b.w (its amount is 2.80 gram/kilogram ethanol), the clothes back is after about 2 minutes, animal is excited, hyperfunction, ataxic gait, and the ability of the animal disequilibrium coordination exercise about 80% is arranged approximately.About about 1 hour husband that fades of above-mentioned symptom changes inhibitory state subsequently over to, the movable minimizing.Gavage the back and recovered normal in 3-4 hour.Gavage every day 1 time, obeyed altogether 14 days.
2.5. the experiment grouping sees Table 7-1 with medication
Table 7-1. experiment grouping and medication
2.6. phagocytic index K and activate the phagocytic capacity α assay method are at first pressed india ink: normal saline=dilution in 1: 9 adds 1% heparin, 20 μ l in every 1ml diluent.Behind last administration 30min, tail vein injection india ink 0.10ml/10g body weight, injection back different time (2min and 20min) is got blood 20 μ l from the eye socket rear vein beard respectively with suction pipe (use in advance heparin solution moistening), is dissolved in 3.0ml 0.1%Na
2CO
3In the solution, put Unic ultraviolet spectrophotometer colorimetric under the 600nm wavelength, measure optical density (OD).At last the dislocation of mice cervical vertebra is put to death, take by weighing liver, spleen and thymic weight respectively.Engulf (cleaning up) index K and activate the phagocytic capacity α by following formula calculating.
K=(logOD
1-logOD
2)/(t
2-t
1)
α=K
1/3* body weight/(liver weight+spleen is heavy)
OD
1, OD
2Be the optical density of different time institute blood sampling, t
2-t
1For getting the time difference of two blood samples.As K, when the α value increases, then explanation has immunological enhancement, can observe trial target with this method and whether have immunostimulant or inhibitory action.
3. experimental result
3.1 influence (seeing Table 7-2) to mice body weight and immune organ weight
Table 7-2.1 side to ethanol institute to the immunologic hypofunction mice
The influence of thymus and index and spleen index
Annotate: # compares with normal group: #P<0.05;
*Compare with the ethanol group:
*P<0.05.
The table 7-2 shown in: mouse gavaging ethanol 2.8 gram/kilograms, gavage 14 days continuously, body weight and thymus index obviously descend, with the normal control group than difference remarkable (P<0.05); Gavage the mice of No. 1 square wine, gavage 14 days continuously, body weight and thymus index increase significant difference (P<0.05) with the ethanol group than obvious.
3.2. influence (seeing Table 7-3) to phagocytic index
Shown in the table 7-3: mouse gavaging ethanol 2.8 gram/kilograms, gavage 14 days continuously, phagocytic index and activate the phagocytic capacity significantly reduce, with the normal control group than the remarkable (P<0.05-0.01) of difference; Gavage the mice of No. 1 square wine, after taking 14 days, phagocytic index and activate the phagocytic capacity significantly improve with ethanol group ratio, and both significant differences (P<0.05-0.001)
Table 7-3.1 side to ethanol institute to the immunologic hypofunction mice
The influence of mononuclear cell phagocytic index and activate the phagocytic capacity
Annotate: # compares with normal group:
##P<0.01;
*Compare with the ethanol group:
*P<0.05,
*P<0.01.
From above result as seen, ethanol can significantly reduce mice body weight and thymus index, and No. 1 square wine and ethanol group ratio can obviously improve mice body weight and thymus index, both significant differences (P<0.01).Ethanol can significantly reduce mononuclear cell phagocytic index and activate the phagocytic capacity, can suppress the reduction of mononuclear cell phagocytic index and activate the phagocytic capacity due to the ethanol for No. 1.The result shows, there is the effect that improves immunologic function No. 1 side to immunologic hypofunction animal due to the ethanol.
Experimental example 8:1 number square wine causes the improvement effect of memory dysfunction to ethanol
1. test objective: alcoholism can cause that higher nervous activity obstacle and the excited conversion process of neurocyte transform slack-off, show as the prolongation of latency of formation condition reflection, can not form trace conditioned reflex, very flexible, bradykinesia, coordination is poor, and going down appears in difficult concentrating, learning and memory.Water maze behavioristics method of testing is used in this test, observes No. 1 side ethanol is caused whether memory dysfunction has the improvement effect.
2. materials and methods:
2.1. tried trial target: dehydrated alcohol, with experimental example 3; No. 1 square wine is with experimental example 3.
2.2. animal: the KM mice, female, body weight 18-22g.
2.3. learning memory disorder model preparation: with reference to above experiment, when once gavaging the ability that has 80% mice disequilibrium to coordinate in ethanol 2.8 gram/kilogram 1-2 hours; By water maze test, gavage ethanol 2.8 gram/kilogram mices, there was 90% mice to seek platform in back 24 hours at clothes and fails, and trained no obvious progress through 3 days.
2.4. water maze test: in medication to 2 week, begin to carry out the ability of learning and memory test.Morris water maze laboratory device is a diameter 120cm round pool, high 50cm; In establish the white platform of a planar diameter 6cm, height 2cm, its distance of center circle pond center of circle 30cm is apart from pool wall 30cm, not in 0.5cm under water; 4 equidistant points on the pool wall are divided into 4 quadrants with the pond.The pond is enclosed object of reference and is remained unchanged, and water temperature is 25 ± 1 ℃, leads and looks for the time of seeking underwater platform in 90 seconds, as the achievement of location learning and memory.
2.5. experiment grouping and medication (seeing Table 8-1).
Table 8-1. experiment grouping and medication
*Carried out the water maze test behind the medicine in 24 hours.
2.6. observation index: (1.) record mice is put into water, seeks and arrives platform required time (seeking the platform time); (2.) mice is put into the number of times (water maze test errors) that water is sought the platform failure.
3. statistical is rolled over: experimental data is represented with mean ± standard deviation, with t check or X
2Carry out significance test.
4. experimental result
4.1. to seeking the influence of platform time
Mice gavages 2.8 gram/kilogram ethanol every day, gavages 14 days continuously, at every turn in obeying back 24 hours, carries out the water maze test, and it the results are shown in Table 8-2
Show 8-2.1 number square wine to the mice water maze test seek the influence of platform time
Annotate: # and normal control group ratio: #P<0.05;
*Compare with the ethanol group:
*P<0.05.
Shown in table 8-2: water maze is tested the 4th, 6 and 8 day ethanol group mice and is sought the platform time and obviously prolong, with matched group than difference remarkable (P<0.05); No. 1 square wine animal seeks the platform time and all is starkly lower than the ethanol group in test process, wherein the 4th, 6,8 day significant difference has significant difference (P<0.05) with ethanol group ratio.
4.2. the number of animals (seeing Table 8-3) of platform failure is sought in test to water maze
Table 8-3.1 side tests the influence of seeking the platform frequency of failure to the mice water maze
Table 8-3 shows, relatively, though no difference of science of statistics, the ethanol group frequency of failure and normal group be than showed increased between the number of times that the water maze test animal is sought the platform failure was organized, and No. 1 square wine and ethanol group are than the trend that minimizing is arranged.
The above results shows, harmful brain function health of drinking for a long time, and very flexible, bradykinesia, coordination is poor, and going down appears in difficult concentrating, learning and memory.Infringement has certain effect that alleviates to the ethanol brain function in No. 1 side, to promoting that ability of learning and memory is useful.
By above experimental study result as seen, gavaging No. 1 square wine mice improves significantly than gavaging the motion of ethanol mice coordinated balance merely, show mainly that animal falls that number reduces and the beginning drop-out time prolongs after obviously, this shows that Radix Rehmanniae or its extract have the effect that improves coordinated balance moving equilibrium imbalance after drinking.In addition, Radix Rehmanniae or its extract are significantly increased the effect of animal hypoxia-bearing capability, have anti-stress effect; Immunologic hypofunction animal due to the ethanol there is the effect that improves immunologic function; And ethanol brain function infringement had certain effect that alleviates, to promoting that ability of learning and memory is useful.
Experimental example 9:3 number square wine causes the influence of anoxia in mice to ethanol
1. experiment purpose: anoxia is a kind of stressor, can cause that body produces various irritabilitys reactions, and this test objective is to observe No. 3 sides whether the ethanol anoxia in mice is had the improvement effect.
2. materials and methods:
2.1. tried trial target: dehydrated alcohol, with experimental example 4; No. 3 square wine are with experimental example 4.
2.2. animal: the KM mice, female, body weight 18-22g.
2.3. experimental technique: body weight is differed the mice random packet that is no more than 2g, after the last administration 30 minutes, respectively mice is put into the airtight wide mouthed bottle of volume identical (250ml), the sodica calx (10g) of equal quantities is housed in the bottle, to absorb moisture and carbon dioxide.Bottleneck is coated with vaseline, bottleneck is sealed after putting into mice.Observe the mouse breathing dwell time with stopwatch.Calculate and respectively organize death time average ± standard deviation, make significance between t test comparable group.
2.4. experiment grouping and medication: see Table 9-1.
Table 9-1. experiment grouping and medication
Group | Dosage (g/kg) | Number of animals (only) | Medication |
Normal control | Drinking water | 10 | 1 time, behind the medicine 30 minutes, irritate stomach |
Ethanol | 2.8 | 10 | 1 time, behind the medicine 30 minutes, irritate stomach |
No. 3 square wine | Ethanol 2.8+3 number square powder 0.4 | 10 | 1 time, behind the medicine 30 minutes, irritate stomach |
3. experimental result: see Table 9-2.
Table 9-2.3 side is to the influence of mice anoxia enduring
Group | Dosage (g/kg) | Number of animals (only) | Hypoxia endurance time (branch) |
Normal control | Drinking water | 10 | 38.5±4.9 |
Ethanol | 2.8 | 10 | 36.8±5.0 |
No. 3 square wine | Ethanol 2.8+3 number square powder 0.4 | 10 | 44.9±5.8 * |
Annotate:
*Compare with the ethanol group:
*P<0.05.
The result shows that behind the mouse gavaging 2.8 gram/kilogram ethanol, hypoxia endurance time decreases than normal control animal, and the mice hypoxia endurance time of taking No. 3 square wine is than ethanol group significant prolongation, significant difference (P<0.05).To show that No. 3 sides are significantly increased the animal hypoxia-bearing capability, have anti-stress effect.
Experimental example 10:3 number square wine is to immunologic hypofunction mice due to the ethanol
The phagocytotic influence of mononuclear cell
Shape foreign bodies more commonly used, as colloidal-carbon, india ink, Chinese prepared Chinese ink,
51The veins such as mutant erythropoietin of Cr labelling are removed by the monokaryon phagocyte rapidly after injecting mice or rabbit blood circulation, are mainly settled down the macrophage at liver and spleen.If the foreign body amount is constant, the speed of then eliminating from blood flow can reflect the phagocytic function of mononuclear phagocyte.
1. experiment purpose: observe No. 3 sides to the cytophagic influence of immunologic hypofunction mouse monokaryon due to the ethanol.
2. materials and methods
2 test materials:
2.1 trial target title
The preparation of dehydrated alcohol and No. 3 square wine and use are with experimental example 4.
2.2. reagent india ink (black ink) is commercially available, Beijing chemical reagents corporation product.Lot number: 0070920.
2.3. animal is the same, the KM mice is male, body weight 18-22g.
2.5 immunologic hypofunction Preparation of model mouse gavaging concentration is 17.7% ethanol, gavaging volume is 0.2ml/10g.b.w (its amount is 2.80 gram/kilogram ethanol), the clothes back is after about 2 minutes, animal is excited, hyperfunction, ataxic gait, and the ability of the animal disequilibrium coordination exercise about 80% is arranged approximately.About about 1 hour husband that fades of above-mentioned symptom changes inhibitory state subsequently over to, the movable minimizing.Gavage the back and recovered normal in 3-4 hour.Gavage every day 1 time, obeyed altogether 14 days.
2.5. the experiment grouping sees Table 10-1 with medication.
Table 10-1. experiment grouping and medication
2.6. phagocytic index K and activate the phagocytic capacity assay method are at first pressed india ink: normal saline=dilution in 1: 9 adds 1% heparin, 20 μ l in every 1ml diluent.Behind last administration 30min, tail vein injection india ink 0.10ml/10g body weight, injection back different time (2min and 20min) is got blood 20 μ l from the eye socket rear vein beard respectively with suction pipe (use in advance heparin solution moistening), is dissolved in 3.0ml 0.1%Na
2CO
3In the solution, put Unic ultraviolet spectrophotometer colorimetric under the 600nm wavelength, measure optical density (OD).At last the dislocation of mice cervical vertebra is put to death, take by weighing liver, spleen and thymic weight and thymus respectively.Connect following formula calculating and engulf (cleaning up) index K and activate the phagocytic capacity α.
K=(logOD
1-logOD
2)/(t
2-t
1)
α=K
1/3* body weight/(liver weight+spleen is heavy)
OD
1, OD
2Be the optical density of different time institute blood sampling, t
2-t
1For getting the time difference of two blood samples.As K, when the α value increases, then explanation has immunological enhancement, can observe medicine with this method and whether have immunostimulant or inhibitory action.
3. experimental result
3.1 influence (seeing Table 10-2) to mice body weight and immune organ weight
Table 10-2.3 side to ethanol institute to the immunologic hypofunction mice
The influence of thymus and index and spleen index
Annotate: # compares with normal group: #P<0.05;
*Compare with the ethanol group:
*P<0.05,
*P<0.01.
As show shown in the 10-2: mouse gavaging ethanol 2.8 gram/kilograms, gavage 14 days continuously, body weight and thymus index obviously descend, with the normal control group than difference remarkable (P<0.05); Gavage the mice of No. 3 square wine, gavage 14 days continuously, body weight and thymus index increase significant difference (P<0.05) with the ethanol group than obvious.
3.2. influence (seeing Table 10-3) to phagocytic index
Shown in the table 10-3: mouse gavaging ethanol 2.8 gram/kilograms, gavage 14 days continuously, phagocytic index and activate the phagocytic capacity significantly reduce, with the normal control group than the remarkable (P<0.05-0.01) of difference; Gavage the mice of No. 3 square wine, after taking 14 days, phagocytic index and activate the phagocytic capacity significantly improve with ethanol group ratio, and both significant differences (P<0.05-0.001).
Table 10-3.3 side to ethanol institute to the immunologic hypofunction mice
The influence of mononuclear cell phagocytic index and activate the phagocytic capacity
Group | Dosage (g/kg) | Number of animals (only) | Phagocytic index (K) | Activate the phagocytic capacity (α) |
Normal control | Drinking water | 10 | 0.0303±0.0073 | 5.0556±0.5908 |
Ethanol | 2.8 | 10 | 0.0159±0.0073 ### | 4.1534±0.4482 ## |
No. 3 square wine | Ethanol 2.8+3 number square powder 0.4 | 10 | 0.0275±0.0085 ** | 4.6610±0.3334 * |
Annotate: # compares with normal group:
##P<0.01;
*Compare with the ethanol group:
*P<0.05,
*P<0.01.
From the result as seen, ethanol can significantly reduce mice body weight and thymus index, and No. 3 square wine and ethanol group ratio can obviously improve mice body weight and thymus index, both significant differences (P<0.01).Ethanol significantly reduces mononuclear cell phagocytic index and activate the phagocytic capacity, can suppress that mononuclear cell phagocytic index and activate the phagocytic capacity reduce due to the ethanol for No. 3.Show that there is the effect that improves immunologic function No. 3 sides to immunologic hypofunction animal due to the ethanol.
Experimental example 11:3 side causes the improvement effect of memory dysfunction to ethanol
1. test objective: alcoholism can cause that higher nervous activity obstacle and the excited conversion process of neurocyte transform slack-off, show as the prolongation of latency of formation condition reflection, can not form trace conditioned reflex, very flexible, bradykinesia, coordination is poor, and going down appears in difficult concentrating, learning and memory.Water maze behavioristics method of testing is used in this test, observes No. 3 sides ethanol is caused whether memory dysfunction has the improvement effect.
2. materials and methods:
2.1. be subjected to the reagent thing: the preparation of dehydrated alcohol and No. 3 square wine and use are with experimental example 4.
2.2. animal: the KM mice, female, body weight 18-22g is the same.
2.3. learning memory disorder model preparation: with reference to above experiment, when once gavaging the ability that has 80% mice disequilibrium to coordinate in ethanol 2.8 gram/kilogram 1-2 hours; By water maze test, gavage ethanol 2.8 gram/kilogram mices, there was 90% mice to seek the platform failure at clothes in back 24 hours, and trained the no obvious progress of nothing through 3 days.
2.4 water maze test: in medication to 2 week, begin to carry out the ability of learning and memory test.Morris water maze laboratory device is a diameter 120cm round pool, high 50cm; In establish the white platform of a planar diameter 6cm, height 2cm, its distance of center circle pond center of circle 30cm is apart from pool wall 30cm, not in 0.5cm under water; 4 equidistant points on the pool wall are divided into 4 quadrants with the pond.The pond is enclosed object of reference and is remained unchanged, and water temperature is 25 ± 1 ℃, leads and looks for the time of seeking underwater platform in 90 seconds, as the achievement of location learning and memory.
2.5 experiment grouping and medication (seeing Table 11-1)
Table 11-1. experiment grouping and medication
*Carried out the water maze test behind the medicine in 24 hours.
2.6 observation index: (1.) record mice is put into water, seeks and arrives platform required time (seeking the platform time); (2.) mice is put into the number of times (water maze test errors) that water is sought the platform failure.
3. statistical analysis: experimental data is represented with mean ± standard deviation, with t check or X
2Carry out significance test.
4. experimental result
4.1. to seeking the influence of platform time
Mice gavages 2.8 gram/kilogram ethanol every day, gavages 14 days continuously, at every turn in obeying back 24 hours, carries out the water maze test, and it the results are shown in Table 11-2.
Show 11-2.3 number square wine to the mice water maze test seek the influence of platform time
Annotate: # and normal control group ratio: #P<0.05;
*Compare with the ethanol group:
*P<0.05.
By table 11-2 as seen, water maze is tested the 4th, 6 and 8 day ethanol group mice and is sought the platform time and obviously prolong, with matched group than difference remarkable (P<0.05); No. 3 square wine animal all is starkly lower than the ethanol group in test process, and wherein the 4th, 6 day significant difference has significant difference (P<0.05) with ethanol group ratio
4.2. the number of animals (seeing Table 11-3) of platform failure is sought in test to water maze
Show 11-3.3 number square wine to the mice water maze test seek the influence of the platform frequency of failure
Shown in table 11-3, relatively, though no difference of science of statistics, the ethanol group frequency of failure and normal group be than showed increased between the number of times that the water maze test animal is sought platform failure was organized, and No. 3 square wine and ethanol group are than the trend that minimizing is arranged.
The above results shows, harmful brain function health of drinking for a long time, and very flexible, bradykinesia, coordination is poor, and going down appears in difficult concentrating, learning and memory.Infringement has certain effect that alleviates to No. 3 square wine to the ethanol brain function, to promoting that ability of learning and memory is useful.
By above experimental study result as seen, gavage No. 3 square wine mices and improve significantly, show mainly that animal falls that number reduces and the beginning drop-out time prolongs after obviously than gavaging the motion of ethanol mice coordinated balance merely.These No. 3 sides of prompting have and improve the unbalance effect of coordinated balance motion after drinking; Be significantly increased the animal hypoxia-bearing capability, have anti-stress effect; Immunologic hypofunction animal due to the ethanol there is the effect that improves immunologic function; And ethanol brain function infringement had certain effect that alleviates, to promoting that ability of learning and memory is useful.
Claims (10)
1. Radix Rehmanniae or its extract are used for improving the purposes of the medicine or the health promoting product of liver function in preparation.
2. Radix Rehmanniae or its extract are in preparation is used for the treatment of and/or prevention is relevant with liver disease and/or the medicine of disease or the purposes in the health promoting product.
3. Radix Rehmanniae or its extract are used for improving mammal (for example people) and relevant disease or the medicine of condition or the purposes of health promoting product of moving equilibrium imbalance in preparation.
4. Radix Rehmanniae or its extract are used for improving mammal (for example people) disease or the condition relevant with anoxia or are used for disease or the medicine of condition or the purposes of health promoting product anti-and stress be relevant in preparation.
5. Radix Rehmanniae or its extract are used for improving the purposes of mammal (for example people) disease relevant with immunologic hypofunction or the medicine of condition or health promoting product in preparation.
6. Radix Rehmanniae or its extract are used for improving mammal (for example people) disease or the condition relevant with injury of brain function or are used to improve or improve the purposes of the medicine or the health promoting product of memory in preparation.
7. Radix Rehmanniae or its extract are used for the treatment of in preparation, prevention, and/or improve following disease, the medicine of disease or condition or the purposes in the health promoting product: the complete or damage of liver function (for example, repair hepatocyte, improve the hepatocyte oxidation resistance, reduce the content of oxyradical (ROS) in the hepatocyte), disease relevant with liver and/or disease are (for example, disease and/or the disease relevant that cause because of chemical substance (including but not limited to ethanol) with liver, hepatic injury, fatty liver, hepatitis, liver cirrhosis, liver failure, alcoholic fatty liver, acute alcoholic fatty liver, chronic alcoholic fatty liver), disease relevant with the moving equilibrium imbalance or condition are (for example due to chemical substance such as the ethanol, moving equilibrium imbalance after for example drinking), disease that anoxia is relevant or condition are (for example due to chemical substance such as the ethanol, anoxia after for example drinking), with disease that stress be relevant or condition (for example due to chemical substance such as the ethanol, due to after for example drinking stress), disease relevant with immunologic hypofunction or condition are (for example due to chemical substance such as the ethanol, immunologic hypofunction after for example drinking), disease relevant with injury of brain function or condition are (for example due to chemical substance such as the ethanol, injury of brain function after for example drinking), memory low (for example due to chemical substance such as the ethanol, the memory after for example drinking is low).
8. according to each purposes of claim 1~7, wherein said medicine or health promoting product can be used for especially people of mammal, and this mammal especially people uses the amount of this medicine or health promoting product to be equivalent to 3~30g Radix Rehmanniae every day, preferably be equivalent to 4~28g Radix Rehmanniae, more preferably be equivalent to 5~24g Radix Rehmanniae, more preferably be equivalent to 7~20g Radix Rehmanniae again, further preferably be equivalent to 9~15g Radix Rehmanniae.
9. according to each purposes of claim 1~8, wherein said Radix Rehmanniae extract has with the next item down or multinomial feature:
Catalpol is 1: 1~1: 9 with the w/w content ratio of oligosaccharide, preferred 1: 1.2~1: 8;
The content of catalpol is greater than 10%, and preferred 10~40%;
The content of oligosaccharide is greater than 40%, and preferred 40~90%;
The content of catalpol is greater than 10%, and the content of oligosaccharide is greater than 40%.
10. according to each purposes of claim 1~9, also further contain other active substance in wherein said medicine or the health promoting product, preferably, described other active substance is selected from Radix Achyranthis Bidentatae, Radix Rhodiolae or its combination.
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Title |
---|
卞晓岚、郑岚、翟青: "《中药复方制剂对肝损伤的干预作用》", 《中国药师》 * |
蒋莹、赵陆华、严永清、许丽、计一平: "《六味地黄汤及其配伍对过氧化物质及脂褐质含量的影响》", 《中国中药杂志》 * |
赵洁等: "鲜生地治疗慢重肝营血症临床观察"", 《辽宁中医杂志》 * |
陈国新: "《六味地黄丸加味治疗脂肪肝64例》", 《陕西中医》 * |
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