CN106138133B - Fennel seeds general flavone treats the application in premenopausal syndrome drug in preparation - Google Patents
Fennel seeds general flavone treats the application in premenopausal syndrome drug in preparation Download PDFInfo
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- CN106138133B CN106138133B CN201610839027.9A CN201610839027A CN106138133B CN 106138133 B CN106138133 B CN 106138133B CN 201610839027 A CN201610839027 A CN 201610839027A CN 106138133 B CN106138133 B CN 106138133B
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- 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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/235—Foeniculum (fennel)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/35—Extraction with lipophilic solvents, e.g. Hexane or petrol ether
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
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Abstract
The present invention relates to fennel seeds general flavones to treat the application in premenopausal syndrome drug in preparation, fennel seeds general flavone can effectively be solved as sole active agent and preparing the application problem in premenopausal syndrome drug, fennel powder is broken into coarse powder, first petroleum ether refluxing extraction, degreasing；The dregs of a decoction volatilize petroleum ether, and ethyl alcohol is added to impregnate, refluxing extraction, and ethyl alcohol is recovered under reduced pressure to no alcohol taste, adds distillation water dispersion, obtains medical fluid；AB-8 type macroporous absorbent resin on medical fluid discards water elution first with distillation water elution；10% ethanol elution of mass concentration is used again, discards eluent；80% ethanol elution of mass concentration is used again, collects 80% ethanol eluate, ethyl alcohol is recovered under reduced pressure to no alcohol taste, freeze-drying crushes, obtains fennel seeds general flavone, abundant raw material of the present invention, preparation method is simple, easy to operate, high production efficiency, the drug of premenopausal syndrome is treated effective for preparation, the new application for having opened up fennel seeds is the innovation on Chinese medicine, there is significant economic and social benefit.
Description
Technical field
The present invention relates to medicine, especially a kind of fennel seeds general flavone treats answering in premenopausal syndrome drug in preparation
With.
Background technique
Fennel seeds are the dry mature fruit of plant, and acrid flavour is warm-natured.Return liver,kidney,spleen, stomach meridian.There are eliminating cold to stop pain, qi-regulating
The effect of stomach function regulating.Salt fennel seeds have the effect of warm kidney eliminating cold to stop pain.For cold hernia stomachache, the testis swelling and hanging down of either of the testes, dysmenorrhea, abdomen crymodynia,
Abdominal distention, deficiency of food are vomited and diarrhoea.Salt fennel seeds are used for cold hernia stomachache, the testis swelling and hanging down of either of the testes, through abdominal pain of trembling with fear.
There is sex hormone fluctuation before referring to postmenopausal women or reduces caused a series of bodies and spirit in premenopausal syndrome
Mental symptoms.Menopause (menopause) is divided into natural menopause and artificial menopause.Natural menopause refers to that ovarian follicle physiological is exhausted in ovary
Caused menopause；Artificial menopause refers to the excision of two sides ovary underwent operative or the menopause caused by by radiotherapy.Artificial menopause patient is more
Premenopausal syndrome easily occurs, clinical symptoms show themselves in that paramenia, such as palpitaition, dizziness, headache, insomnia, tinnitus often occur
Autonomic imbalance symptom, difficult concentrating, and mood swing is big.Show as exciting irritability, anxious or mood
It is low, depressed, be unable to the emotional symptoms such as self-contr ol, failure of memory is also more typical, affects the health and life of patient
Bioplasm amount.
Though existing have a variety of drugs for treating premenopausal syndrome, so far there are no the fennel seeds extracted from fennel seeds are total
Flavones treats the application in premenopausal syndrome drug in preparation.
Summary of the invention
For above situation, for the defect for overcoming the prior art, it is always yellow that the purpose of the present invention is just to provide a kind of fennel seeds
Ketone treats the application in premenopausal syndrome drug in preparation, can effectively solve fennel seeds general flavone and exist as sole active agent
Prepare the application problem in premenopausal syndrome drug.
The technical solution that the present invention solves is that fennel powder is broken into coarse powder, first petroleum ether refluxing extraction, degreasing；Fennel fruit
Incense drug slag volatilizes petroleum ether, and ethyl alcohol is added to impregnate, refluxing extraction, and filtering is recovered under reduced pressure ethyl alcohol to no alcohol taste, adds distillation water dispersion,
Obtain medical fluid；AB-8 type macroporous absorbent resin on medical fluid discards water elution first with distillation water elution；Mass concentration 10% is used again
Ethanol elution discards eluent；80% ethanol elution of mass concentration is used again, collects 80% ethanol eluate, ethyl alcohol is recovered under reduced pressure
It to no alcohol taste, is freeze-dried, crushes, obtain fennel seeds general flavone.
Fennel seeds general flavone prepared by the present invention is treated in premenopausal syndrome drug as sole active agent in preparation
Application, abundant raw material, preparation method is simple, easy to operate, high production efficiency, treats premenopausal syndrome effective for preparation
Drug has opened up the new application of fennel seeds, is the innovation on Chinese medicine, there is significant economic and social benefit.
Specific embodiment
It elaborates below in conjunction with concrete condition to a specific embodiment of the invention.
In specific implementation, fennel seeds general flavone is premenopausal in preparation treatment as sole active position (ingredient) by the present invention
Application in syndrome drug, the fennel seeds general flavone are the coarse powder that fennel powder was broken into 20-30 mesh, first overstriking powder 10
The petroleum ether refluxing extraction 1h of times weight, degreasing, the fennel seeds dregs of a decoction volatilize petroleum ether, overstriking powder 10 times of weight, mass concentrations
80% ethyl alcohol impregnates 0.5h, refluxing extraction 1h, and filtering obtains first time filtrate；The dregs of a decoction 10 times of weight, mass concentrations of overstriking powder again
80% alcohol reflux extracts 1h, and filtering obtains second of filtrate, merges filtrate twice, ethyl alcohol is recovered under reduced pressure to no alcohol taste, adds distillation
Moisture, which is dissipated to, is equivalent to 0.3g/ml containing crude drug amount, obtains medical fluid；AB-8 type macroporous absorbent resin on medical fluid is first steamed with 2 times of column volumes
Distilled water elution, discards water elution；Again with 10% ethanol elution of mass concentration of 4 times of column volumes, eluent is discarded；Again with 6 times
80% ethanol elution of mass concentration of column volume collects 80% ethanol eluate, ethyl alcohol is recovered under reduced pressure to no alcohol taste, freezing is dry
It is dry, it crushes, obtains fennel seeds general flavone.
For the present invention through testing, it is premenopausal comprehensive to can be effectively used for preparation treatment as sole active agent for fennel seeds general flavone
The drug of simulator sickness, related testing data are as follows:
1 experimental material
1.1 medicine and reagent
Fennel seeds general flavone of the present invention, content > 56%；Geng Nian An Capsules are (glutinous rehmannia, Rehmannia glutinosa, rhizoma alismatis, Radix Ophiopogonis, radix scrophulariae, male
The root bark of tree peony, Poria cocos, mother-of-pearl, thizoma curculiginis, Schisandra chinensis, magnetite, the vine of multiflower knotweed, uncaria, Fructus Tritici Levis, prepared fleece flower root), nourishing and suppressing Yang, relieving restlessness
Calm the nerves；For climacteric hectic fever sweating, dizziness and tinnitus, irritated insomnia.Specification: every dress 0.3g；Usage and dosage: it is oral, one
Secondary 3,3 times a day), Shanxi Yellow River Traditional Chinese Medicine Co., Ltd..Rat E2 detection kit, R&D company；Benzylpenicillin sodium for injection,
Huabei Pharmaceutic Co., Ltd, specification: 4,000,000 units；Formalin (analysis pure), Chemical Co., Ltd. in pairs, Yantai City；
0.9% sodium chloride injection, Henan Cologne pharmaceutcal corporation, Ltd；Chloraldurate: accurate chemical institute is recovered in Tianjin；Wine
Essence: big disinfectant preparation Co., Ltd, Xinxiang City three.
1.3 laboratory apparatus
TDZ4-WS table-type low-speed centrifuge, Hunan Xiang Yi Laboratory Instruments development corporation, Ltd.；BIORAD-680 enzyme mark
Instrument, 680Microplate Reader, Bio-Rad Laboratories；BX61 electric microscope, Japanese OLYMPUS company；
Manual liquid transfering device, Thermo Fisher Scientific Inc., the U.S., model: JZ19600；
HHS-21-8 type electric-heated thermostatic water bath, Medical Equipment Plant, Shanghai Boxun Industrial Co., Ltd.；BCD-248T type ice
Case, Xin Fei Electrical Appliances Co., Ltd；1000 electronic scale of JM, Yuyao note inscription weighing calibration equipment Co., Ltd；
AL204 electronic balance, Mettler-Toledo Instrument (Shanghai) Co., Ltd..
1.4 experimental animal
Cleaning grade mouse, Kunming kind, female, 18-22g, Lukang Medical Co., Ltd., Shandong, animal certificate number
37005400000020；Laboratory quality certification number SYXK (Henan) 2010-001.
2 experimental methods
2.1 modelings and administration
Modeling method: taking Kunming mouse 70, and female, 22~25g takes 60 mouse at random, and penta bar of ratio is injected intraperitoneally
Abdomen position is fixed after appropriate sodium 50mg/kg anesthesia, then under back of mice most end rib cage, in midaxillary line and away from about 1cm on the outside of backbone
Skin and dorsal muscles about 0.5~1cm are cut in infall cropping after disinfection, the shinny cellulite of a visible milky in the notch visual field,
Ovary embeds wherein.It gently clamps cellulite with pincet to pull out outside notch, fractionation of fatty group, i.e., visible one thin-line-shaped
Irregular is in the ovary of yellowish red color.First fallopian tubal under ovary (including fat) is ligatured with filament when clip, then extracts ovary, art
After take advantage of a situation and put back to cornua uteri in abdominal cavity, suture muscle and skin, extract bilateral ovaries with method.Separately taking 10 mouse is blank pair
It according to group, performs an operation by upper method, but does not cut off ovary.Careful postoperative raising, the prevention infection of intramuscular injection penicillin, continuous 3d.Hand
Start to perform an operation mouse after art 5d by only progress rat vagina plate coating checking, 1 time a day, continuous 5d, to determine whether ovary is complete
Full excision.Smear is presented the animal emotionally reacted and is discarded, and 60 complete animals of castration is selected to be uniformly divided into 5 groups at random.
Respectively model group, Geng Nian An Capsules group, large and small dosage fennel seeds general flavone group are singly performed an operation not ovariectomized for blank
Control group.
Medication: CMC-Na is dissolved in the distilled water boiled, 0.5% solution is made as solvent, will be following
Each drug is suspended wherein.Take the large and small dosage of fennel seeds general flavone: 20mgmL-1、10mg·mL-1, by 400mgkg-1、
200mg·kg-1Stomach-filling；Geng Nian An Capsules: 33.75mgmL-1, by 675mgkg-1Stomach-filling (is equivalent to the 15 of quantity
Times) stomach-filling；Model group and blank group give the CMC-Na solution of same volume, and administered volume is 0.2mL/10g, 1 time a day, even
It is 3 weeks continuous.
2.2 observation items and detection method
2h (fasting 15 hours) after each group mouse last stomach-filling, socket of the eye venous blood sampling are separated serum, are surveyed using radioimmunology
Determine E in serum2, LH, FSH content；Mouse is dissected, thymus gland, spleen, uterine tissue is extractd, weighs its weight in wet base and calculate internal organs
Index (organ index=organ wet weight mg/ rat body weight g)；Uterus is fixed in 10% formalin solution, paraffin embedding,
Slice, HE dyeing, the histomorphological changes of light microscopic observation each group.
The measuring method of estradiol
Measuring principle: this experiment uses radioimmunoassay method.Calibration object or sample, marker and antibody are first pressed into journey
Sequence regulation sequentially adds in test tube, and label and non-labeled antigen is made to compete with one another for combining with finite quantity antibody, after equilibrium to be reacted,
Release agent is added, centrifugation separates free antigen with antigen antibody complex, measures the radioactive intensity of sediment.With
E2 content increases, and radioactive intensity then accordingly reduces.
Calibrating reagent:125I-E2, 1 bottle (red liquid)；
Antibody, 1 bottle (blue liquid)；
Calibration object, 7 bottles (liquid), concentration 0,10,50,100,250,750,2000pg/mL；
Release agent, 1 bottle (suspension) with before shaking up；
Quality controlled serum, contains low, high two dosage by 2 bottles (liquid).
Operation sequence: by round bottom polystyrene tube number (by multiple pipe operation), according to the form below procedure operation
It is loaded mensuration program list position: μ L
Data processing: related parameter, calibration curve and sample concentration are directly given with γ calculating instrument program prepared in advance.
Experimental result
The influence of 3.1 pairs of climacteric model mice organ indexs
Fennel seeds general flavone is shown in Table 1 to the influence for enclosing premenopausal Syndrome Model mouse thymus, spleen, uterus index.
Influence of the 1 fennel seeds general flavone of table to premenopausal Syndrome Model mouse thymus, spleen, uterus index is enclosed
Note: compared with model group, P < 0.01 * P < 0.05, * *
It can be seen that from upper table, and blank control group ratio, the thymus index of model group mouse, index and spleen index and uterus index are equal
It significantly reduces (P < 0.01), illustrates that extracing ovary leads to climacteric model mice thymus gland, spleen and the atrophy in uterus.With model
Group ratio, fennel seeds general flavone large dosage group and Geng Nian An Capsules group be remarkably improved model mice thymus index (P < 0.01),
Fennel seeds general flavone small dose group can significantly improve model mice thymus index (P < 0.05)；The large and small dosage of fennel seeds general flavone
Group and Geng Nian An Capsules group are remarkably improved model mice index and spleen index (P < 0.01)；Fennel seeds general flavone large dosage group and more
Pacify Capsules group in year and is remarkably improved model mice uterus index (P < 0.01).
The influence of 3.2 pairs of climacteric model mice E2 levels
Fennel seeds general flavone is to enclosing premenopausal Syndrome Model mice serum E2Horizontal influence is shown in Table 2.
2 fennel seeds general flavone of table is to enclosing premenopausal Syndrome Model mice serum E2Horizontal influence
Note: compared with model group, P < 0.01 * P < 0.05, * *
It can be seen that from upper table, and blank control group ratio, E2 level is remarkably decreased (P < 0.01) in model group mice serum, says
Bright excision ovary leads to the sex hormone level disorder in climacteric model mice serum, and climacteric mouse model is copied into
Function.With model group ratio, the large and small dosage group of fennel seeds general flavone and Geng Nian An Capsules group are remarkably improved model mice serum E2
Horizontal (P < 0.01).
The influence of 3.3 pairs of climacteric model mice uterus histomorphologies
Naive mice Uterine mucosa layer, muscle layer, placenta percreta are normal, and epithelial cell, mucous glands are normal in mucous layer.Mould
Type group Mouse Uterus mucous layer, muscle layer, the obvious atrophy of placenta percreta, there is atrophy and subtract in epithelial cell, mucous glands in mucous layer
It is few.Geng Nian An Capsules group Mouse Uterus mucous layer, muscle layer, placenta percreta obtain a degree of recovery, epithelial cell in mucous layer,
Mucous glands is also centainly restored.Fennel seeds general flavone large dosage group Mouse Uterus mucous layer, muscle layer and placenta percreta obviously obtain
Restore, epithelial cell, mucous glands obviously restore in mucous layer.Fennel seeds general flavone small dose group Mouse Uterus mucous layer, muscle layer
And placenta percreta slightly restores, epithelial cell, mucous glands slightly restore in mucous layer.
Using the widest part and the most narrow place of micrometer measurement endometrium and muscle layer thickness, mean is sought, with method of counting, meter
Body of gland quantity in inner membrance is calculated, seeks mean, survey the results are shown in Table 3.
3 fennel seeds general flavone of table to enclose premenopausal Syndrome Model endometrium of mouse, in muscle layer and inner membrance body of gland shadow
It rings
Note: compared with model group, P < 0.01 * P < 0.05, * *
It can be seen that from upper table, with blank control group ratio, model group endometrium of mouse thickness, muscle layer thickness substantially reduce (P
< 0.01), body of gland number significantly reduces (P < 0.01), illustrates that mouse makes metratrophia after climacteric model, body of gland is reduced.With
Model group ratio, fennel seeds general flavone large dosage group and Geng Nian An Capsules group can dramatically increase model mice endometrium thickness (P
< 0.01) model mice mesometrium thickness (P < 0.01), can be dramatically increased, gland in model mice endometrium can be dramatically increased
Body quantity (P < 0.01).
There should be this product to treat the drug (capsule) of premenopausal syndrome for curing the disease, and through the 68 light of the true standard of clinical diagnosis
Premenopausal syndrome patient's clinical application is spent, significant clinical effectiveness is achieved.It is patient daily 3 times, 2-3 each, often
The grain 0.5g of general flavone containing fennel seeds, monthly 1 course for the treatment of, is used in conjunction 2 courses for the treatment of.In addition to 2 people, clinical symptoms disappear or clinical symptoms have
It is obviously improved or 66 people of improver, effective percentage is up to 97.1%.Getting well for effect was not expected, was the premenopausal syndrome for the treatment of
Innovation on drug, has opened up the new application of fennel seeds, and economic and social benefit is significant.
Claims (1)
1. a kind of fennel seeds general flavone treats the application in premenopausal syndrome drug in preparation as sole active position, this is small
Fennel general flavone is the coarse powder that fennel powder was broken into 20-30 mesh, the petroleum ether refluxing extraction of 10 times of weight of first overstriking powder
1h, degreasing, the fennel seeds dregs of a decoction volatilize petroleum ether, and 10 times of weight of overstriking powder, 80% ethyl alcohol of mass concentration impregnate 0.5h, refluxing extraction
1h, filtering, obtains first time filtrate；10 times of weight of overstriking powder, 80% alcohol reflux of mass concentration extract 1h to the dregs of a decoction again, and filtering obtains the
Secondary filtrate merges filtrate twice, ethyl alcohol is recovered under reduced pressure to no alcohol taste, adds distilled water to be dispersed to and is equivalent to 0.3g/ containing crude drug amount
Ml obtains medical fluid；AB-8 type macroporous absorbent resin on medical fluid first distills water elution with 2 times of column volumes, discards water elution；Again with 4
10% ethanol elution of mass concentration of times column volume, discards eluent；Again with 80% ethanol elution of mass concentration of 6 times of column volumes,
80% ethanol eluate is collected, ethyl alcohol is recovered under reduced pressure to no alcohol taste, is freeze-dried, crushes, obtain fennel seeds general flavone.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475237A (en) * | 2002-08-13 | 2004-02-18 | 孙兴望 | Medicine for strengthening yang and tonifying kidney, treating male infecundity and male and female climacteric syndrome |
| CN102091115A (en) * | 2011-03-07 | 2011-06-15 | 河南中医学院 | Epimedium extract for treating climacteric syndrome |
| CN104083473A (en) * | 2014-07-24 | 2014-10-08 | 河南中医学院 | Application of raspberry extract in preparation of drug for treating perimenopausal syndrome |
-
2016
- 2016-09-21 CN CN201610839027.9A patent/CN106138133B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475237A (en) * | 2002-08-13 | 2004-02-18 | 孙兴望 | Medicine for strengthening yang and tonifying kidney, treating male infecundity and male and female climacteric syndrome |
| CN102091115A (en) * | 2011-03-07 | 2011-06-15 | 河南中医学院 | Epimedium extract for treating climacteric syndrome |
| CN104083473A (en) * | 2014-07-24 | 2014-10-08 | 河南中医学院 | Application of raspberry extract in preparation of drug for treating perimenopausal syndrome |
Non-Patent Citations (1)
| Title |
|---|
| "补肾阳中药治疗围绝经期综合征特点分析";魏珍珍等;《中医学报》;20131101;第28卷(第11期);第1690页左栏倒数第1-5行、右栏倒数第11-17行 * |
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