CN101214338B - New use of Chinese medicine compound pharmaceutical composition - Google Patents
New use of Chinese medicine compound pharmaceutical composition Download PDFInfo
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- CN101214338B CN101214338B CN2008100000788A CN200810000078A CN101214338B CN 101214338 B CN101214338 B CN 101214338B CN 2008100000788 A CN2008100000788 A CN 2008100000788A CN 200810000078 A CN200810000078 A CN 200810000078A CN 101214338 B CN101214338 B CN 101214338B
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Abstract
The present invention provides a medicine compound including the following raw materials with the weight portions such as 18 to 30 portions of prepared rehmannia rhizome, 9 to 12 portions of cornus dogwood fruit, 8 to 16 portions of Chinese yam, 9 to 12 portions of medlar, 8 to 16 portions of field dodder and 8 to 16 portions of deerhorn glue, and the purpose in preparing the medicine for delaying vaginal aging. The medicine is an active medicine for strengthening external gonad tissue aromatase and a medicine for increasing vaginal blood supply. The medicine is a medicine for preventing or/and curing senile vaginitis. Under a specific diagnosis standard, the medicine provided by the present invention has definite efficacy. The medicine has the advantages of same efficacy on delaying vaginal aging, few raw materials, wide sources, effective cost saving due to selection of raw materials, no effect on the level of serum estrogen after long-term administration, no proliferation on endometrium and safety. The present invention provides a new choice for clinically curing senile vaginitis, in particular preventing senile vaginitis or recurrence of senile vaginitis.
Description
Technical field
The present invention relates to a kind of new purposes of traditional Chinese compound medicine compositions, particularly, is to delay purposes in the wither medicine of vagina in preparation.
Background technology
Estrogen mainly exists with two kinds of molecular forms: estrone (estrone, E
1) and estradiol (estradiol, E
2), E
1And E
2Can transform mutually.Because E
1Biological activity have only E
2About 1%, so E
2It is estrogen molecule with physiological significance.Non-gravid woman's ovary is the major organs of synthetic estrogen before the menopause, and (testosterone Te) is converted into E with testosterone
2A small amount of estrogen also can be synthesized in other position, comprises the fatty tissue mesenchymal cell
[1], skin flbroblast, osteoblast, bone chondrocyte, cardiovascular endotheliocyte and arterial smooth muscle cell, HPOA, AH, hypothalamus substrate and corpus amygdaloideum also can synthetic estrogens in addition, these cells and be organized in women's menopause after promptly become the synthetic main site of body inner estrogen.The outer estrogen synthesis of gonad has the feature different with the ovary synthetic estrogen: at first, the outer synthetic estrogen of gonad be with in paracrine, the cell or the mode of extracellular autocrine act on the local organization cell
[2], [3]Combine with EBG estrogen-binding globulin because circulation estrogen is most of, can not directly act on estrogen receptor, thus the outer tissue of gonad synthesize partial TO may be seldom, but concentration height, biological effect is strong.Secondly, because gonad is organized the ability that lacks synthetic C19 steroidal compounds outward, utilizing circulation C19 steroidal compounds is that the outer metaplasia of gonad produces estrogenic primary condition.The androstenedione that the outer tissue of postmenopausal women's gonad mainly produces with adrenal cortex is the catalytic action generation E that substrate passes through aromatase
1, be converted into active strong E again
2Play a role.
Studies show that much fatty tissue can not only storage power, the endocrine organ that still can secrete multiple hormonal substance
[4], [5]Obese women osteoporosis sickness rate is lower, thin body's osteoporosis morbidity risk rate height, and reason is in the obese women body that blood estradiol or estriol are higher
[6]Follow weight increase, androstenedione is converted into estrogen to be increased, and sex hormone binding globulin reduces in the blood, causes that free estrogen level raises, so estrogen in body weight and the circulation and E
2Level is proportionate
[7]Women's body inner estrogen level after menopause descends, and lipophilia is arranged, and illustrates that the reduction of estrogen level may and be brought out fat relevant with lipid metabolism.There are some researches show that estrogen is the important regulatory factor that adipose cell differentiation and body fat distribute
[8]Reports such as Wing, the perimenopausal women weight average is annual to increase by 1 pound, and mainly is the increase of fatty tissue, and is central obesity, and abdominal circumference has tangible increase
[9], this is consistent with the research that menopausal women fat centration is gathered
[10]There is document to think that aromatase plays an important role on the distribution of regulating fatty tissue and size, often occurs stomach fat deposition (waistline increase) after women's menopause, may be relevant with the overexpression of postmenopausal women fatty tissue aromatase mRNA.The aromatase mRNA overexpression. cause the local estrogen level to increase, change body fat and distribute, the interior fat deposition
[11], and healthy postmenopausal women's interior fat is being made and is being transformed on the estrone more even more important than periphery fat
[12]People's such as Zhu Xiaohui the lipid metabolism that oophorectomize obviously influences mice that studies show that causes abdominal cavity fat to gather, exogenous estrogen intervention, particularly prolonged application, and the abdominal cavity fat that can obviously reduce mice gathers.And exogenous estrogen intervention is to the not significantly influence of normal mouse peritoneal fat
[13]Foreign literature report menopausal women gives the entad distribution that controversies in hormone replacement in the elderly can stop or reverse fat
[14], [15]Liu Yi etc. also think long-term Hormone Replacement Therapy (hormone replacement therapy, HRT) can not increase the weight of to prevent the increase of the body weight relevant, body fat with menopause, yet HRT group women waistline is significantly less than matched group women (P＜0.05), shows that long-term HRT has to help prevent fatty ventrad to shift
[16], this result of study is consistent with the result of study of Haarbo etc.
[17], the increase of the variation of postmenopausal women's estrogen level and body fat is described and gathers to present certain dependency.
Intravital low estrogen state can cause a series of degenerative disease behind the postmenopausal women, and as osteoporosis, vagina is wither and Alzheimer etc., senile vaginitis is the wither special performance of vagina.Senile vaginitis is common in postclimacteric elderly woman, in addition, also can cause the generation of primary disease behind excision bilateral ovaries, premature ovarian failure, the pelvic irradiation.Clinical manifestation is: the ovarian function decline, and estrogen level reduces, the vaginal wall atrophy, easily film attenuation, glycogen content reduces in the epithelial cell, and the intravaginal pH value rises, and therefore local resistance reduces, and pathogen is invaded breeding easily and causes inflammation.Vaginal mucosa is senile change, and the wrinkle wall disappears, and epithelium is poor, mucous hyperemia, and the surface is dispersed in little petechia or petechial hemorrhage speckle, and cervix uteri is also normal congested, is dispersed in little petechia.Sometimes can form the vaginal mucosa adhesion, even atresia of vagina causes pyometra.Vaginal mucosa is a pale red, is dispersed in little scarlet point, can see shallow aphtha sometimes.See under the mirror that vagina epithelium comes off, go up subcutaneous connective tissue hyperemia, leukocyte infiltration.
The clinical manifestation of senile vaginitis is: a period of time per vaginam is very clean after the menopause, but engenders dried itch or dry and astringent, and may seldom have secretions this moment, or a small amount of faint yellow secretions is arranged.Gynecologial examination can be found vaginal wall attenuation and light, is dispersed on the mucosa or the point-like hyperemia or the oozing of blood of volume.
Therefore,, all can be diagnosed as senile vaginitis if meet following standard, that is: women's menopause, or bilateral ovaries is excised; Vaginal secretions increases, and is thin, faint yellow, and severe patient is blood sample, pus; Pruritus vulvae, causalgia, part patient's frequent micturition, dysurea; Vaginal mucosa atrophy, pleat disappear, mucosa hyperemia, redness, visible petechia, the visible ulcer of severe patient.
Usually, the treatment senile vaginitis is the physiological characteristics local application according to vagina, strengthens its protective effect.At first, 1. adopt the vagina and vulva ablution, cleanout fluid is suitable acid, remedying the situation that old physiological acidity dies down, and available 1% lactic acid or 0.5% acetate solution washing vagina.As far as possible without the demibain of potassium permanganate (p.p) liquid, in case hold improper or life-time service causes the local skin mucosa because more dried phenomenon of itching appears in astriction because of concentration.2. to note keeping the pudendum health, use warm water every night and clean once.3. in conjunction with old characteristics, can be under physician guidance, part or whole body use the estrogen partner treatment, and complementing estrogen is the effective ways of this disease of treatment.But estrogenic untoward reaction reaction mainly is that the gastrointestinal reaction side effect is to cause that vaginal secretions increases.As take estrogenic women, have 5～10% side effect to occur, as hemorrhage, abdominal distention, edema, lower abdomen take out pain, breast is swollen etc., how when beginning to take, to occur, with then dying away long afterwards.Estrogen is when being used for the treatment of senile vaginitis in addition, and to other adjacent organs, as the influence of other organ indexs such as uterus, life-time service easily causes pathological changes even canceration.In addition, serious hepatic renal dysfunction, hematoporphyria, systemic lupus erythematosus (sle), suffer from activeness vein or arterial thrombosis disease etc. in 6 months, should forbid estrogen.Because the limitation of controversies in hormone replacement in the elderly at present, adopts Chinese medicine women Senile disease that its unique curative effect is usually arranged.
Left and right " eight gusts of the new sides of Jing Yue's complete work " of returning ball to come from Ming Dynasty temperature compensation famous expert Zhang Jingyue is the classics side of benefiting kidney-YIN, kidney yang, all can be used for treating all diseases in women's menopause front and back clinically.Bolus as a Kidney-Yin-Tonic treatment perimenopausal syndrome, can eliminate symptoms such as warming sweating, irritated irritability, dry mouth and throat, can increase vaginal secretions, improve pudendum, vaginal dryness symptom, the amenorrhea of oestrogen deficiencies is also had curative effect (Zhu Ling, Chen Binbin preferably, netherworld intelligence, Deng. Bolus as a Kidney-Yin-Tonic clinical experimental research progress [J]. traditional Chinese medical science forum, 2003,18 (2): 51-53.) " Bolus as a Kidney-Yin-Tonic " control Kidney-Yin deficiency of kidney-YIN, can not nourish battalion and defend, gradually to weak, or the deficiency-heat contact, spontaneous sweating, or mental derangement, blood are not returned former, or deficient impairment of YIN, or lose to drench and can't help, or deficiency of vital energy dusk transports, or the dim eyesight deafness, or the dry mouth dry tongue, or waist soreness, lose in all marrow, body fluid dries up and waits card, and all speed should strengthening renal yin to inhibit predominant yang, training the Kidney-Yin of left kidney, and essence and blood is from filling, suitable this side master's." Yougui Wan, the kidney-Yang-Reinforcing Bolus " controls first YANG deficiency, or first native endowments decline, or impairment caused by overstrain is excessive, so that decline of the fire from the gate of life can not the immature soil, and be Deficiency and coldness of spleen and stomach, diet advances less, or the vomiting and nausea expansion, or kind stomach is dysphagic, or timid cold fear is cold, or the many pains of umbilicus abdomen, or loose stool, dysentery is done frequently, or little water self discard, the empty colic of cold type that drenches, or cold invade trench and the podomere arthralgia pain, or tremble with fear at the part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels and the pathogenic water edema.In a word, the insufficiency of kidney-YANG person must the Mental fatigue timidness due to deficiency of QI, or heart beating is not peaceful, or limbs do not receive, or soon evil haunt and plague, or the sun cards such as loss of fecundity that decline, the suitable benefit fire of all speed former, and training the Yuanyang of right kidney, and manner is improved oneself, this side master's.
Document: modern clinical practice of Bolus as a Kidney-Yin-Tonic and recent progress in experimental study, Chinese experimental pharmacology of Chinese medical formulae magazine 2004,10 (1) has reported that Bolus as a Kidney-Yin-Tonic is used for the treatment of the frequently-occurring disease of menopausal women---atrophic vulvitis.From diseased region, the atrophic vulvitis position is at pudendum, and atrophic vulvovaginitis has just been contained vagina; The cause of disease that causes atrophic vulvitis not exclusively is that estrogen level lowly causes, and as the white diseases of vulva that the cause of disease imperfectly understands, wherein " atrophic type " can show as the vulvovaginal atrophy.Therefrom the angle of medical drugs is seen, because the Bolus as a Kidney-Yin-Tonic effect is enriching yin and nourishing kidney, life essence-filling, marrow-benefitting cures mainly the marrow loss, and sun loses to dive to be contained, and envelope is hidden the kidney-YIN being deficient card due to the mistake department.The Yougui Wan, the kidney-Yang-Reinforcing Bolus warming and recuperating the kidney-YANG, life essence-filling, marrow-benefitting is used for insufficiency of kidney-YANG, syndrome of decline of vital gate fire.There were significant differences aspect the concrete indication of the traditional Chinese medical science.When at same indication with doctor trained in Western medicine diagnostic criteria definition, because differential diagnosis in tcm is inequality, the selection of medicine is different.Chinese medicine has traditional advantage aspect the treatment Senile disease, yet at one with the definite disease of doctor trained in Western medicine standard diagnostics, if do not pass through the doctor of formal training, when the clinical practice Chinese medicine, tend to because of can not correctly dialectical and wrong medication, cause clinical use inconvenience, be not easy to diagnosing the accurate medication of definite disease, the while also makes troubles to patient and wastes.At present still do not have the left and right ball of returning and be used to delay the wither relevant report of vagina.
Summary of the invention
Technical scheme of the present invention has provided a kind of new purposes of traditional Chinese compound medicine compositions.Particularly, be to delay purposes in the wither medicine of vagina in preparation.Another technical scheme of the present invention has provided a kind of wither pharmaceutical composition of vagina that delays.
The invention provides and contain pharmaceutical composition that the following weight proportion raw material is prepared from and delay purposes in the wither medicine of vagina: Radix Rehmanniae Preparata 18-30 part, Fructus Corni 9-12 part, Rhizoma Dioscoreae 8-16 part, Fructus Lycii 9-12 part, Semen Cuscutae 8-16 part, Colla cornus cervi 8-16 part in preparation.
Wherein, described medicine is the medicine that increases the confession of vagina blood.Wherein, described medicine is organized the active medicine of aromatase outward for strengthening gonad.
Wherein, described medicine is that prevention is or/and the medicine of treatment senile vaginitis.
Described senile vaginitis, its patient is normal type or the patient who is lower than normal type.
Described normal type standard judges that by the normal type international standard surpassing normal 20% is overweight body weight.
Wherein, described pharmaceutical composition is to be prepared from by the following weight proportioning:
24 parts in Radix Rehmanniae Preparata, Fructus Corni 9-12 part, 12 parts of Rhizoma Dioscoreaes, Fructus Lycii 9-12 part, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis.
Further preferably, also contain 9 parts of Radix Cyathulaes, 12 parts of Colla Plastri Testudiniss in the described raw material.Still more preferably, described pharmaceutical composition is to be prepared from by the following weight proportion raw material:
24 parts in Radix Rehmanniae Preparata, 12 parts of Fructus Corni, 12 parts of Rhizoma Dioscoreaes, 12 parts of Fructus Lycii, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis, 9 parts of Radix Cyathulaes, 12 parts of Colla Plastri Testudiniss.
Further preferably, also contain 12 parts of the Cortexs Eucommiae, 6 parts of Cortex Cinnamomis, 9 parts of Radix Angelicae Sinensis, 6 parts of Radix Aconiti Lateralis Preparata in the described raw material.
Still more preferably, described pharmaceutical composition is to be prepared from by the following weight proportion raw material:
24 parts in Radix Rehmanniae Preparata, 9 parts of Fructus Corni, 12 parts of Rhizoma Dioscoreaes, 9 parts of Fructus Lycii, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis, 12 parts of the Cortexs Eucommiae, 6 parts of Cortex Cinnamomis, 9 parts of Radix Angelicae Sinensis, 6 parts of Radix Aconiti Lateralis Preparata.
The present invention also provides a kind of wither pharmaceutical composition of vagina that delays, and it is to contain the medicament that is prepared from by the following weight proportion raw material:
Radix Rehmanniae Preparata 18-30 part, Fructus Corni 9-12 part, Rhizoma Dioscoreae 8-16 part, Fructus Lycii 9-12 part, Semen Cuscutae 8-16 part, Colla cornus cervi 8-16 part.
Further, it is to be prepared from medicament by containing by the following weight proportion raw material:
24 parts in Radix Rehmanniae Preparata, Fructus Corni 9-12 part, 12 parts of Rhizoma Dioscoreaes, Fructus Lycii 9-12 part, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis.
Further, it is the medicament that is prepared from by the following weight proportion raw material:
24 parts in Radix Rehmanniae Preparata, Fructus Corni 9-12 part, 12 parts of Rhizoma Dioscoreaes, Fructus Lycii 9-12 part, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis.
This pharmaceutical composition provided by the invention delays the wither new purposes of vagina.Especially have and strengthen the activity that gonad is organized the active of aromatase outward and increased the confession of vagina blood.At the treatment normal type or be lower than the patient of normal type.Under specific diagnostic criteria, drug effect is clear and definite.Especially directly the pharmaceutical composition that adopts Radix Rehmanniae Preparata, Fructus Corni, Rhizoma Dioscoreae, Fructus Lycii, Semen Cuscutae, Colla cornus cervi Six-element raw material in the compatibility scope that the present invention limits, to be prepared into, compare with traditional left and right ball of returning, brought into play identical effect aspect wither delaying vagina, and raw material is few, wide material sources, cost can be effectively saved in the selection of raw material, taking does not for a long time have influence to the serum estrogen level, and endometrium is not had proliferation function, has safety.Be the clinical treatment senile vaginitis, especially prevent senile vaginitis or the recurrence of prevention senile vaginitis that new selection is provided.
The specific embodiment
The preparation (Bolus as a Kidney-Yin-Tonic) of embodiment 1 pharmaceutical composition 1 of the present invention
Take by weighing raw material: Radix Rehmanniae Preparata 200g, Semen Cuscutae 100g, Radix Achyranthis Bidentatae 75g, Colla Plastri Testudinis 100g, Colla cornus cervi 100g, Rhizoma Dioscoreae 100g, Fructus Corni 100g, Fructus Lycii 100g;
Preparation method: above eight flavors, except that Colla cornus cervi, Colla Plastri Testudinis, Six-elements such as all the other Radix Rehmanniae Preparata are ground into fine powder, and mixing sieves.Get Colla cornus cervi, Colla Plastri Testudinis molten, with above-mentioned fine powder mixing.Every 100g powder adds refined honey 10g and an amount of water, general ball, and drying, promptly.
The preparation (Yougui Wan, the kidney-Yang-Reinforcing Bolus) of embodiment 2 pharmaceutical compositions 2 of the present invention
Take by weighing raw material: Radix Rehmanniae Preparata 24g, Rhizoma Dioscoreae 12g, Fructus Corni 9g, Fructus Lycii 9g, Semen Cuscutae 12g, Colla cornus cervi 12g, Cortex Eucommiae 12g, Cortex Cinnamomi 6g, Radix Angelicae Sinensis 9g, Radix Aconiti Lateralis Preparata 6g.
Preparation method: Radix Rehmanniae Preparata is steamed mashed pestle cream, and surplus is smalls, adds making pellets by mixing medical powder with honey, big as pellet shot from a slingshot.Whenever chew clothes two or three balls (6～9g), send down to roll plain soup.
The preparation of embodiment 3 medicines of the present invention
Take by weighing raw material: Radix Rehmanniae Preparata 24g, Fructus Corni 12g, Rhizoma Dioscoreae 12g, Fructus Lycii 12g, Semen Cuscutae 12g, Colla cornus cervi 12g;
Preparation method: above Six-element, except that Colla cornus cervi, Six-elements such as all the other Radix Rehmanniae Preparata are ground into fine powder, and mixing sieves.Get the Colla cornus cervi molten, with above-mentioned fine powder mixing.Every 100g powder adds refined honey 10g and an amount of water.
The preparation of embodiment 4 medicines of the present invention
Take by weighing raw material: Radix Rehmanniae Preparata 24g, Fructus Corni 9g, Rhizoma Dioscoreae 12g, Fructus Lycii 9g, Semen Cuscutae 12g, Colla cornus cervi 12g;
Press the preparation of embodiment 3 methods.
The preparation of embodiment 5 medicines of the present invention
Take by weighing raw material: Radix Rehmanniae Preparata 18g, Fructus Corni 9g, Rhizoma Dioscoreae 8g, Fructus Lycii 9g, Semen Cuscutae 8g, Colla cornus cervi 8g; Press the preparation of embodiment 3 methods.
The preparation of embodiment 6 medicines of the present invention
Radix Rehmanniae Preparata 30g, Fructus Corni 12g, Rhizoma Dioscoreae 16g, Fructus Lycii 12g, Semen Cuscutae 16g, Colla cornus cervi 16g, the method preparation of pressing embodiment 3.
Above-mentioned raw materials can be used crude drug in whole, also can use the processed product of crude drug in whole.
Below be by effect experiment and clinical trial certificate beneficial effect of the present invention.
Experiment material and instrument
1, experiment material
Bolus as a Kidney-Yin-Tonic (preparation of embodiment 1 method): the fair envelope shore pharmaceutical Co. Ltd of going up of Shanghai thunder, adult's dosage 18g/ day, lot number: 040810, its high low dosage group is called for short respectively: " left side is high, a left side is low ".
Yougui Wan, the kidney-Yang-Reinforcing Bolus (preparation of embodiment 2 methods): the Tongrentang Pharmaceutical Factory, Beijing TongrenTang Co., Ltd, adult's dosage 27g/ day, lot number: 4013139, its high low dosage group is called for short respectively: " right high, right low ".
Premarin: the Ayerst pharmaceutical factory production of Hui Shi Ayerst drugmaker (specification: the 0.625mg/ sheet), lot number: PKG0404001
Pentobarbital sodium: China Medicine's import packing, lot number: F20020405
Gentamicin injection liquid: Tianjin Pharmaceutical Jiaozuo Co., Ltd., lot number: 04081002-2
ZHUSHEYONG LIUSUAN LIANMEISU: Huabei Pharmaceutic Co., Ltd, lot number: 040704
Benzylpenicillin sodium for injection: Huabei Pharmaceutic Co., Ltd, lot number: U0406610
Normal saline: Sichuan Meida Kangjiale Pharmaceutical Co., Ltd., lot number: 05030631
Estradiol test kit: Alpha Diagnostic International company, lot number: 05114-B
The essential minimal medium of high sugared Da Erbaike (family name) (dulbecco ' s minimum essentialmedium, DMEM): GIBCO company.Lot?No：1272921。
Testosterone Propionate injection: 25mg/ml, 10/box, Shanghai General Pharmaceutical Co., ltd., lot number: 020711
3-isobutyl-1-methylxanthine (isobuthyl-methylxan-thine, IBMX), dexamethasone (dexamethasone, Dex), (insulin Ins) all purchases the company in sigma to insulin
Trypsin:Sigma company, lot number: 032K7255
Newborn calf serum: the biological company limited of Harry, lot number: 050109
Trizol：Takara，Lot：B201A
RT-PCR test kit: Takara, Lot:BK3101
Mouse aromatase primer, rat aromatase primer: Shanghai Shenergy Biocolor BioScience ﹠ Technology Company.
Dehydrated alcohol: Anhui An Te biochemistry corporation,Ltd., lot number: 0510073604.
Chloroform: 1Guanghua Chemical Plant Co., Ltd., Guangdong, lot number: 20051114.
Isopropyl alcohol: 1Guanghua Chemical Plant Co., Ltd., Guangdong, lot number: 20050526.
Agarose: Bio-west, Lot:081527
PBS, EDTA, TAE, pyrocarbonic acid diethyl ester (diethylpyrocarbonarate, DEPC) all fresh configuration for the treatment of water, agarose gel.
2, experimental apparatus
Electronic balance: German Sartorius BS210S
Low speed centrifuge: Beijing Medical Centrifugal Machine Factory, LD5-2A
Inverted microscope: Japanese OLYMPUS CK40
CO
2Incubator: German HERAEUS BB5060
Small-sized high speed centrifugal machine: U.S. Thermo 3591
Microplate reader: U.S. Thermo MK3
High speed refrigerated centrifuge: BECKMAN Allegra 64R
Desk centrifuge: eppendorf 5415D
Constant temperature roaster: go up the grand experimental facilities company limited of Nereid, DHG-9053A
Ultraviolet spectrophotometer: Beckman DU640
Electrophoresis tank, electrophresis apparatus: BIORAD PAC 200
PCR instrument: Hybaid HBPX 220
Gel imaging system and image analysis software: Kodak EDAS 290 and Kodak 1D 3.5
Medical image analysis system of safe alliance 2000
Primer 5.0 primer-design softwares
Agitator, superclean bench, ultra cold storage freezer, 0.22 μ m syringe needle filter, cell counting count board, 6 well culture plates, 24 well culture plates, EP pipe, single track micropipettor, multichannel micropipettor, loading slot etc.; 1ml, 5ml syringe, No. four, No. five syringe needles, stitching thread, sewing needle, needle forceps, the ophthalmology tweezer, operating scissors is dissected plate, aseptic cotton carrier, microscope slide.
Experimental example 1 medicine mice serum estradiol E2 pH-value determination pH of the present invention
1, laboratory animal and method
1.1 laboratory animal and environment
45 of the female ♀ child-bearing period of Kunming kind mices, body weight 18 ± 2g purchases the Experimental Animal Center in the institute of Chinese materia medica, Sichuan, the quality certification: No. 19, the real moving Guan Zhidi in river, the conventional raising of cleaning level Animal House.22～25 ℃ of room temperatures, humidity 45%～65%, the light and shade time of replacing is 12: 12 hours round the clock.
1.2 animal grouping and administration
Under the situation of body weight homogeneous, mice is divided into 3 groups at random, is respectively normal group, the high group in a left side and right high group, 15 every group.Gavage normal saline, Bolus as a Kidney-Yin-Tonic (0.06g/10g), Yougui Wan, the kidney-Yang-Reinforcing Bolus (0.09g/10g) respectively, irritate the long-pending 0.3ml/10g that is of body of stomach.
1.3 the preparation of disposable filling stomach pastille mice serum
Every group of mice in administration 0.5 hour, got 3 capable femoral artery in 2 hours, 4 hours, 8 hours, 24 hours respectively and get blood, the gained hematology lab is gentle and quiet put 2 hours after, centrifugal 3000 * g, 15 minutes.Get upper serum, every component dress is preserved with 0.22 μ m filtering with microporous membrane degerming postposition-70 ℃ refrigerator.
1.4 the 3T after the differentiation is induced in all kinds of serum cultivations
3-L
1Preceding adipose cell
3T
3-L
1Before adipose cell be Green and Kehinde in separating clone gained from the Swiss3T3 mice embryonic in 1974, be the cell strain that the research of generally acknowledging in the world at present becomes the fat process, can simulate the function of live body fatty tissue preferably
[18], [19], can be used as the experiment in vitro carrier that research fatty tissue aromatase is expressed
[20], [21]The expression of aromatase is the sign of adipose cell before not breaking up, and the expression that preceding adipose cell is divided into sophisticated adipose cell and aromatase descends relevant.Because the expression of aromatase and active at 3T
3-L
1Preceding adipose cell is divided in the adipose cell process the highest
[22], so we select to induce the 3T in the differentiation
3-L
1Preceding adipose cell carries out the research of aromatase activity and expression.
1.4.13T
3-L
1The cultivation of preceding adipose cell
3T
3-L
1Preceding adipose cell is provided by buchu group natural drug screening center.From liquid nitrogen, take out 3T
3-L
1Preceding adipose cell, 37 ℃ of water-baths recoveries.Centrifugal 3 minutes of the cell suspension 1000 * g of recovery abandons supernatant, add contain 10% newborn calf serum (New bron calf serum, NCS), the high sugared DMEM culture fluid of penicillin 100u/L, streptomycin 100u/L makes 2 * 10
5The cell suspension of/ml adds six porocyte culture plates, places in 37 ℃ of incubators (5% carbon dioxide, 95% air) culture fluid of replacing in per 48 hours.
1.4.23T
3-L
1Before adipose cell induce differentiation
Inoculating cell 5 * 10
4/ hole is in 24 well culture plates, cultivate after 1 day, reference literature (JianbeiDeng, Kunjie Hua, Steven S.Lesser and Joyce B.Harp.Activation ofSignal Transducer and Activator of Transcription-3 duringProliferative Phases of 3T3-L1 Adipogenesis.Endocrinology.2000,141 (7): 2370-2376; Zhu Xiaohai, He Qinglian, the woods person of outstanding talent, etc. the foundation [J] of adipose cell cultivation and propagation and differentiation model before the people. Chinese shaping burns unit magazine .1999,15 (3): 199-201) induce differentiation.
Cultivate 3T 1.4.3 add all kinds of serum
3-L
1Preceding adipose cell
Induce differentiation after 48 hours, change culture fluid, make in the high sugared DMEM culture fluid that does not contain NCS and only contain 10mg/L Ins, substrate T, the serum that adds high, the right high group day part 2%, 10% in a normal group serum of 2%, 10% and a left side respectively, other establishes no T (containing 2% normal group mice serum), no T serum-free group is to contrast.
1.5 measure 3T
3-L
1The E of preceding adipose cell supernatant
2Value
Add all kinds of serum cultured cells 48 and after 96 hours, the observation of cell metamorphosis is got cell conditioned medium 100 μ l, 3000 * g measures E after centrifugal 5 minutes
2Value.In strict accordance with the enzyme linked immunological kit description operation, in microplate reader 450nm absorbance, (optical density OD), makes standard curve according to the concentration and the OD value of standard substance, calculates E in the sample to read absorbance
2Concentration.
2, result
2.1 a left side high group day part variable concentrations pastille serum is cultivated 3T
3-L
1Before adipose cell 48 and cell conditioned medium E after 96 hours
2Value
2.1.1. the table 1 left side preceding adipose cell of high group day part 2% pastille serum cultivation 3T3-L1 cell conditioned medium E2 value (pg/ml) after 48 hours
2.1.2 table 2 left side high group day part 2% pastille serum is cultivated 3T
3-L
1Preceding adipose cell cell conditioned medium E after 96 hours
2Value (pg/ml)
2.1.3 table 3 left side high group day part 10% pastille serum is cultivated 3T
3-L
1Preceding adipose cell cell conditioned medium E after 48 hours and 96 hours
2Value (pg/ml)
| Group | E behind the cultivation 48h 2(pg/ml) | Cultivate E after 96 hours 2(pg/ml) |
| A high 4h left side, a high 2h left side, a no T normal left high 0.5h left side high 8h high 24h in a left side | 16.98±3.79 31.37±1.12 34.16±0.09 38.09±1.57 41.98±8.46 23.21±5.67 21.30±1.46 | 15.33±0.02 31.03±9.41 24.47±1.47 35.28±3.10 38.48±11.67 21.61±6.96 18.27±0.00 |
Table 1, table 2 and table 3 prompting, Bolus as a Kidney-Yin-Tonic high dose are irritated stomach and are had certain promotion during pastille Mus serum 2% concentration after 8 hours and cultivate the effect of adipose cell aromatase activity before the 3T3-L1 after 48 hours.The Bolus as a Kidney-Yin-Tonic high dose is irritated stomach and is had certain promotion during pastille Mus serum 10% concentration after 4 hours and cultivate the effect of adipose cell aromatase activity before the 3T3-L1 after 96 hours.The Bolus as a Kidney-Yin-Tonic high dose is irritated stomach and is had certain promotion during pastille Mus serum 10% concentration after 4 hours and cultivate the effect of adipose cell aromatase activity before the 3T3-L1 after 48 or 96 hours.
2.2 right high group day part variable concentrations pastille serum is cultivated 3T
3-L
1Before adipose cell 48 and cell conditioned medium E after 96 hours
2Value
2.2.1 the right high group day part 2% pastille serum of table 4 is cultivated 3T
3-L
1Preceding adipose cell cell conditioned medium E after 48 hours
2Value (pg/ml)
2.2.2 the right high group day part 10% pastille serum of table 5 is cultivated 3T
3-L
1Before adipose cell 48 and cell conditioned medium E after 96 hours
2(pg/ml)
| Group | E behind the cultivation 48h 2(pg/ml) | Cultivate E after 96 hours 2(pg/ml) |
| The right high 24h of the no T right high 8h of the right high 4h of the right high 2h of normal right high 0.5h | 16.98±3.79 31.37±1.12 33.43±2.84 34.79±11.88 60.35±16.99 34.76±13.12 27.38±11.78 | 15.33±0.02 31.03±9.41 23.42±4.19 38.60±2.78 75.79±0.91 103.15±0.00 33.56±7.06 |
The prompting of table 4, table 5, Yougui Wan, the kidney-Yang-Reinforcing Bolus high dose are irritated stomach and are had certain promotion during pastille Mus serum 10% concentration after 4 hours and cultivate the effect of adipose cell aromatase activity before the 3T3-L1 after 48 or 96 hours.
Above-mentioned mouse experiment proves, left and right activity of returning ball can strengthen the preceding adipose cell aromatase of 3T3-L1.
Experimental example 2 medicine rat blood serum estradiol E of the present invention
2Value
Experimental technique: press experimental example 1 described mice serum estradiol E
2The experimental technique of value is measured.
1, laboratory animal and environment
Normal type rat: the female ♀ SD of child-bearing period rat, 230 ± 30g, 97; Purchase Experimental Animal Center, raise, the quality certification: SCXK (river) 2004-11 in the secondary Animal Lab. in Chengdu University of Traditional Chinese Medicine.22～25 ℃ of room temperatures, humidity 45%～65%, the light and shade time of replacing is 12: 12 hours round the clock.
Overage and overweight rats: the female ♀ SD of child-bearing period rat, body weight: 279g～464g, 157; Irritate the stomach time: 12 weeks.Wherein, the rat above normal type about 20% is an overage and overweight rats.
2, the foundation of castration model and animal grouping
The rat adaptability was fed after 7 days, except that normal group (20), and the pentobarbital sodium (30mg/kg of equal intraperitoneal injection of saline preparation, 1ml/100g), the abdomen position is fixed, and sham operated rats (17) is closed abdomen after only removing ovary fatty tissue on every side, all the other (60) row removal ovaries operations.Postoperative is the injection of antibiotics prevention infection for three days on end, and the vaginal smear of after this going is observed, and continuous 5 days, every day 1 time, rat did not have the oestrous cycle performance after the castration, determines the castration success.Rat with the castration success under the situation of body weight homogeneous is divided into 6 groups, castration normal saline group (8), premarin group (11), the high group in a left side (6), Bolus as a Kidney-Yin-Tonic low dose group (the low group in a left side, 9), right high group (6), Yougui Wan, the kidney-Yang-Reinforcing Bolus low dose group (right low group, 9), normal group, sham operated rats, castration normal saline group all gavages normal saline, the high group in a left side, the low group in a left side gavages Bolus as a Kidney-Yin-Tonic (0.6g/100g respectively, 0.15g/100g), right high group, right low group gavages Yougui Wan, the kidney-Yang-Reinforcing Bolus (0.9g/100g respectively, 0.23g/100g), premarin group 1 gavages rat premarin (62.5ug/100g), premarin group 2 gavages mice premarin (41.7ug/100g), and every 0.625mg medicine is joined the 15ml pure water, medicine is pressed into Powdered, be bundled into parcel, every day matching while using.Every treated animal is irritated the long-pending 1ml/100g that is of body of stomach, takes by weighing body weight one time, and adjusts dosage in three days.Perfusion begins vaginal smear and observes vaginal cell keratinization rate, all 11 weeks of continuous irrigation stomach after 2 weeks.
3, the preparation of continuous irrigation stomach pastille rat blood serum
The continuous irrigation stomach is after 11 weeks, rat last administration 1 hour
[23]Back row femoral artery is got blood, and after blood left standstill 2 hours, centrifugal 3000 * g 15 minutes, got upper serum, the grouping mixing.All serum are all used the filtering with microporous membrane degerming of 0.22 μ m.
4,3T
3-L
1Before adipose cell cultivation and induce differentiation with experimental example 1
5, pastille serum is cultivated 3T
3-L
1Preceding adipose cell
Induce differentiation after 48 hours, change culture fluid, make in the high sugared DMEM culture fluid that does not contain NCS only to contain Ins10mg/L and substrate T.Add and respectively organize serum, final concentration is 2%; Set up no pastille serum group (containing 2%NCS and T), no T to organize (containing 2%NCS), cultivated 48 hours.
6,3T
3-L
1Preceding adipose cell cell conditioned medium E
2The mensuration of value
Cultivate after 48 hours, observe every group of cellular morphology and change, get cell culture fluid 50 μ l, 3000 * g gets supernatant and measures E after centrifugal 5 minutes
2Value.In strict accordance with the enzyme linked immunological kit description operation, in microplate reader 450nm absorbance, read the OD value, the drawing standard curve.
7, method and result:
Female child-bearing period rat is divided into normal group, sham operated rats and castration group, is divided into castration normal saline group, premarin group, Bolus as a Kidney-Yin-Tonic high dose group, Yougui Wan, the kidney-Yang-Reinforcing Bolus high dose group after the castration group castration.Normal group, sham operated rats, castration normal saline group gavage normal saline, the high group in a left side gavages Bolus as a Kidney-Yin-Tonic, right high group gavages Yougui Wan, the kidney-Yang-Reinforcing Bolus, the premarin group gavages premarin, and every treated animal is irritated the long-pending 0.3ml/10g that is of body of stomach, and administration is got uterine cancer cell and done the pathology section after 45 days.Continuous irrigation stomach 11 all backs femoral artery are got blood, measure serum E
2Value is got uterus, vagina tissue and is done the pathology section, obtains simultaneously to contain medicine castration Mus serum of the present invention, contain premarin castration Mus serum and contain normal saline castration Mus serum.Cultivate 3T with 2% all kinds of serum
3-L
1Preceding adipose cell is measured cell conditioned medium E after 48 hours
2Value.
The high low dosage of table 6 medicine of the present invention is to castrated rats serum E
2The influence of value (pg/ml)
| Group | Normal type rat group | The overage and overweight rats group | ||
| Sample number (n) | Serum E2 value | Sample number | Serum E 2Value | |
| A high left side, normal sham-operation sham-operation in rutting period of normal dioestrus in a rutting period dioestrus castration normal saline premarin group left side is low right high right low | ?10?10?7?10?8?11?6?9?6?9 | 61.67±24.36 28.30±13.38 61.56±13.50 36.77±14.49 16.28±5.96▲▲■◆ 530.32±295.97* 28.13±15.23◆ 17.80±6.63▲▲■◆ 19.08±5.43▲◆ 21.84±8.01▲◆ | 15 13 12 9 10 9? | 321.14±83.51 320.09±33.81 244.67±24.63 222.66±68.23 225.55±36.63 179.23±34.46? |
Annotate: compare ■ P＜0.05 ■ ■ P＜0.01 ■ ■ ■ P＜0.001 rutting period with normal group
Compare P＜0.05 P＜0.01 P＜0.001 with the normal group diestrus
Compare rutting period with sham operated rats, ▲ P＜0.05 ▲ ▲ P＜0.01 ▲ ▲ ▲ P＜0.001
Compare △ P＜0.05 △ △ P＜0.01 △ △ △ P＜0.001 with the sham operated rats diestrus
Compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with castration normal saline group
Compare with the premarin group, ◆ P＜0.05 ◆ ◆ P＜0.01 ◆ ◆ ◆ P＜0.00
Table 6 normal type experiment prompting: high low dose group of medicine of the present invention and castration normal saline group compare, to serum E
2Value does not have obviously influence (P＞0.05), compares serum E with the premarin group
2Be worth variant (P＜0.05).
Overweight experiment prompting, the laboratory animal body weight is too high during castration, and during the body weight that is above standard 1/2 left and right sides, medicine of the present invention is to castration overage and overweight rats serum E
2Value is influence not, (P＞0.05).
Experimental example 1 and 2 shows that medicine of the present invention does not directly increase serum E
2Value has the effect that certain enhancing gonad is organized activity of aromatizing enzyme outward, promotes estrogen synthesis, and it is wither to delay the castrated rats vagina.
Experimental example 3 medicine vagina blood supply effect experiments of the present invention
By vagina pathology pathological section, to observe down at low power lens (10 * 10), the back is taken pictures with software measurement thickness by the thickest, the thinnest and interior thickness 3 places of every routine specimen selection vaginal mucosa; High power lens (40 * 10) is observed down, at mucosa the thickest, the thinnest and interior thickness 3 places respectively number go out the epithelial cell number of plies (with the nucleus location), calculate the meansigma methods of mucosal thickness and the meansigma methods of the epithelial cell number of plies; Adopt low power lens (10 * 10) to observe down, count out all vagina pleats of the whole vagina of each specimen cross section and vagina lamina propria blood vessel number, the result is as follows:
Table 7 medicine of the present invention is to vaginal mucosa thickness, vagina pleat and vagina lamina propria blood vessel number
| The experiment of normal type rat group | |||||
| Grouping | The example number | Mucosal thickness (μ m) | The pleat number | Vagina lamina propria blood vessel number | The epithelial cell number of plies |
| Normal group | 10 | 3.10±0.64 | 16.40±6.69 | 19.00±6.22 | 8.20 ± 1.39 (rutting period) |
| 10 | 2.97±0.69 | 19.10±6.72 | 27.40±15.52 | 8.10 ± 1.66 (dioestruss) | |
| Sham operated rats | 7 | 3.36±0.33 | 11.57±3.91 | 24.84±10.42 | 8.86 ± 1.22 (rutting period) |
| 9 | 2.88±0.87 | 15.78±4.68 | 26.33±5.77 | 8.00 ± 1.73 (dioestruss) | |
| The castration group | 8 | 0.74±0.25 | 10.25±4.59 | 13.13±4.61 | 2.88±0.64 |
| The premarin group | 11 | 3.23±0.40● | 17.64±4.90★ | 34.91±10.90★ | 8.55±1.13● |
| The Bolus as a Kidney-Yin-Tonic group | 6 | 1.03±0.22 | 18.17±6.11★ | 28.33±5.32★ | 3.50±0.55 |
| The Yougui Wan, the kidney-Yang-Reinforcing Bolus group | 8 | 0.89±0.19 | 22.25±7.96★ | 30.63±8.62★ | 3.25±0.46 |
● compare P＜0.05 with castration group, left Yougui Wan, the kidney-Yang-Reinforcing Bolus group
★ and castration group be P＜0.05 relatively
Normal type experiment prompting: under certain body weight (near standard body weight), premarin can obviously improve vaginal mucosa thickness, pleat number, vagina lamina propria blood vessel number, the epithelial cell number of plies of castrated rats, the left and right ball of returning can obviously increase castrated rats vagina pleat and vagina lamina propria blood vessel number, and to the not influence of vaginal mucosa thickness, the epithelial cell number of plies, illustrate that (near standard body weight) can be by improving the confession of vagina blood under certain body weight for medicine of the present invention, it is wither to delay vagina.
Experimental example 4 medicines of the present invention are to the influence of castrated rats body weight
Table 8 gavages the influence of high 11 weeks of low dosage of medicine of the present invention to castration normal type rat body weight difference
| Group | The example number | Irritate the preceding body weight of stomach after the castration | Put to death preceding body weight after irritating stomach | Weightening finish (g) (%) |
| The right low group of the right high group of the low group in a high group left side, a normal group sham operated rats castration contrast premarin group left side | 20 17 8 11 6 9 6 9 | 238.40±10.94 239.94±19.63 255.38±23.98 254.82±20.87 257.57±22.37 253.67±18.14? | 276.40±21.25 279.35±27.15 302.00±28.17 260.64±23.87 310.29±32.21 315.89±53.62? | 38.00±17.67◆◆◆(15.96％±7.35％) 39.41±13.51◆◆◆(16.39％±5.33％) 48.37±20.68◆◆◆(18.08％±6.58％) 5.82±13.49■■■▲▲▲*** (2.34％±5.72％) 52.71±11.51◆◆◆(20.34％±3.15％) 49.77±14.45◆◆◆(18.01％±6.06％) 62.22±52.24(24.71％±20.64％) 52.33±21.67◆◆(21.00％±8.61％) |
Annotate: ■ ■ ■ and normal group compare, P＜0.001
▲ ▲ ▲ compares P＜0.001 with sham operated rats
* * and castration normal saline group compare, P＜0.001
◆ ◆ compare P＜0.01 with the premarin group ◆ ◆ ◆ compare P＜0.001 with the premarin group
Table 8 prompting: left side height, right high group compare administration forebody-afterbody method of double differences there was no significant difference (P＞0.05) with castration normal saline group; Premarin group and castration normal saline group, high, left low the group relatively in a left side, body weight has utmost point significant difference (P＜0.001) before and after the administration; Premarin group and Yougui Wan, the kidney-Yang-Reinforcing Bolus low dose group compare, and body weight has significant difference (P＜0.01) before and after the administration.To sum up, premarin group weight increase is not remarkable, and all the other each groups increase obviously, but group difference not obvious (P＞0.05).
Table 9 medicine of the present invention to overweight experimental rat castration after the influence of body weight
| Grouping | The example number | Irritate the preceding body weight of stomach after the castration | Put to death preceding body weight after irritating stomach | Weightening finish (g) (%) |
| Normal group sham operated rats castration group premarin group Bolus as a Kidney-Yin-Tonic group Yougui Wan, the kidney-Yang-Reinforcing Bolus group | 15 13 12 9 10 9 | 383.07±38.27 366.08±31.85 395.75±44.10 399.22±38.78 399.20±39.84 419.89±49.41 | 440.73±49.00 427.08±49.70 463.25±69.25 405.44±45.39 456.70±60.21 487.33±75.56 | 57.67±40.35(15.35％±10.64％) 61.00±38.40(16.77％±10.49％) 67.50±37.83(16.80％±9.03％) 6.22±20.88●(1.52％±4.92％) 57.50±28.10(14.10％±6.90％) 67.44±36.97(15.85％±9.91％) |
● compare P＜0.05 with normal group, sham operated rats, castration group, left Yougui Wan, the kidney-Yang-Reinforcing Bolus group
Table 8, table 9 prompting, premarin group weightening finish value significantly are lower than all the other each groups (P＜0.05), and it is all more obvious that all the other respectively organize weight increase, but respectively organize group difference not statistically significant (P＞0.05).
(after the castration irritate stomach before) respectively organizes relatively (x ± s) of body weight average before twice experiment of table 10
| Grouping | The example number | Overweight experimental group | The example number | The normal type experimental group | Average difference (overweight %) |
| Normal group sham operated rats castration group premarin group Bolus as a Kidney-Yin-Tonic group Yougui Wan, the kidney-Yang-Reinforcing Bolus group | 15 13 12 9 10 9 | 383.07±38.27 366.08±31.85 395.75±44.10 399.22±38.78 399.20±39.84 419.89±49.41 | 20 17 8 11 7 9 | 238.40±10.94 239.94±19.63 255.38±23.98 254.82±20.87 257.57±22.37 253.67±18.14 | 144.67(60.68％) 126.14(52.57％) 140.37(54.97％) 144.40(56.67％) 141.63(54.99％) 166.22(65.53％) |
Table 10 prompting, the preceding weight ratio of overweight experimental group and normal type experimental group rat experiment, overweight experimental group rat is overweight more obvious.
(irritate stomach then put to death before) respectively organized relatively (x ± s) of body weight average before twice experiment of table 11 put to death
| Grouping | The example number | Overweight experimental group | The example number | The normal type experimental group | Average difference (overweight %) |
| Normal group sham operated rats castration group premarin group Bolus as a Kidney-Yin-Tonic group Yougui Wan, the kidney-Yang-Reinforcing Bolus group | 15 13 12 9 10 9 | 440.73±49.00 427.08±49.70 463.25±69.25 405.44±45.39 456.70±60.21 487.33±75.56 | 20 17 8 11 7 9 | 276.40±21.25 279.35±27.15 302.00±28.17 260.64±23.87 310.29±32.21 315.89±53.62 | 164.33(59.45％) 147.73(52.88％) 161.25(53.39％) 144.80(55.56％) 146.41(47.18％) 171.44(54.27％) |
Table 11 prompting, overweight experimental group and normal type experimental group rat are put to death preceding weight ratio, and overweight experimental group rat is overweight also more obvious.
Above-mentioned experimental result prompting: gavaging the premarin body weight after the rat castration does not have obvious increase.Weight increase is remarkable before and after normal group, sham operated rats, castration group, the medicine group of the present invention experiment, but group difference is not obvious.Normal type experimental group and overweight experimental group result have repeatability.Respectively organize the normal body weight experimental group of body weight mean before and after the overweight experimental group castrated rats experiment and increase 120-170g, average overweight 47%-65%.
Experimental example 5 medicines of the present invention are to the influence of overage and overweight rats vaginal mucosa thickness, vagina pleat and vagina lamina propria blood vessel number
Table 12 medicine of the present invention is to vaginal mucosa thickness, vagina pleat and vagina lamina propria blood vessel number
| The experiment of overage and overweight rats group | |||||
| Grouping | The example number | Mucosal thickness (μ m) | The pleat number | Vagina lamina propria blood vessel number | The epithelial cell number of plies |
| Normal group | 12 | 324.92±59.38 | 17.83±4.82 | 79.50±15.59 | 7.50±1.45 |
| Sham operated rats | 9 | 375.26±78.11 | 15.78±3.70 | 62.50±17.86 | 7.33±1.22 |
| The castration group | 9 | 223.45±71.02 | 23.33±7.40 | 34.67±10.00 | 2.78±0.44 |
| The premarin group | 9 | 399.30±66.38 | 15.89±3.41 | 82.00±30.50● | 7.11±0.93● |
| The Bolus as a Kidney-Yin-Tonic group | 10 | 271.72±61.87 | 23.30±6.57 | 54.70±21.53 | 3.6±2.07 |
| The Yougui Wan, the kidney-Yang-Reinforcing Bolus group | 8 | 239.73±33.60 | 21.37±6.28 | 51.38±11.60 | 2.5±0.76 |
● compare P＜0.05 with castration group, left Yougui Wan, the kidney-Yang-Reinforcing Bolus group
Table 12 prompting, premarin is not obvious to the castrated rats serum estrogen level influence of overweight, but the vagina lamina propria blood vessel number and the epithelial cell number of plies are had appreciable impact, and medicine of the present invention then has no significant effect (P＞0.05) to the castrated rats vagina tissue of overweight.
The experiment of routine 1-5 prompting by experiment, it is wither that medicine of the present invention can delay vagina, has to strengthen the activity that gonad is organized the active of aromatase outward and increased the confession of vagina blood, and medicine of the present invention has the effect that stimulates the adipose cell synthetic estrogen.For normal type rat group, left Yougui Wan, the kidney-Yang-Reinforcing Bolus can obviously improve castrated rats pleat number, lamina propria blood vessel number; And at the experiment of overage and overweight rats group, the laboratory animal body weight is too high during castration, and during the body weight that is above standard 1/2 left and right sides, medicine of the present invention does not have obvious influence to castration overage and overweight rats vagina, and is different with normal type rat group experimental result.
Medicine of the present invention does not have obvious influence (P＞0.05) to the too high castration experimental rat of body weight vagina.Be familiar with reference to the traditional Chinese medical science " fertile people's excessive phlegm " traditional theory, the overweight people is pressed from both sides phlegm-damp more, and medicine of the present invention is based on the kidney invigorating, senile vaginitis due to normal type experiment prompting is fit to suffer from a deficiency of the kidney at treatment, overweight experiment prompting does not have obvious effect for the senile vaginitis that presss from both sides phlegm-damp of suffering from a deficiency of the kidney.
Experimental example 6 drug safety experiments of the present invention
1, uterus weight in wet base and uterus organ index
Table 13 gavages the influence of high 11 weeks of low dosage of medicine of the present invention to castrated rats uterus weight in wet base
| Group | The example number | Weight in wet base (g) |
| A high left side, moving sham-operation in the rutting period dioestrus castration normal saline premarin of normal normal dioestrus sham-operation in a rutting period left side is low right high right low | 10 10 7 10 8 11 6 9 6 9 | 0.67±0.07*** 0.47±0.07*** 0.68±0.09*** 0.50±0.09*** 0.10±0.02■■■□□□▲▲▲△△△◆◆◆ 0.48±0.06*** 0.09±0.02■■■□□□▲▲▲△△△◆◆◆ 0.12±0.03■■■□□□▲▲▲△△△◆◆◆ 0.09±0.03■■■□□□▲▲▲△△△◆◆◆ 0.10±0.02■■■□□□▲▲▲△△△◆◆◆ |
Annotate: ■ ■ ■ organizes relatively P＜0.001 with normal rutting period
compares P＜0.001 with normal diestrus group
▲ ▲ ▲ compares P＜0.001 with sham-operation group in rutting period
△ △ △ and sham-operation diestrus group compare, P＜0.001
* * and castration normal saline group compare, P＜0.001
◆ ◆ ◆ compare P＜0.001 with the premarin group
Table 13 prompting: high low dose group of medicine of the present invention and castration normal saline group compare, uterus weight in wet base there was no significant difference (P＞0.05).
Table 14 gavages the influence of high 11 weeks of low dosage of medicine of the present invention to castrated rats uterus organ index
| Group | The example number | The uterus organ index |
| A high left side, moving sham-operation in the rutting period dioestrus castration normal saline premarin of normal normal dioestrus sham-operation in a rutting period left side is low right high right low | 10 10 7 10 8 11 6 9 6 9 | 0.0025±0.0003*** 0.0016±0.0003*** 0.0024±0.0004*** 0.0018±0.0002*** 0.0003±0.0001■■■□□□▲▲▲△△△◆◆◆ 0.0019±0.0004*** 0.0003±0.0001■■■□□□▲▲▲△△△◆◆◆ 0.0004±0.0001■■■□□□△△△◆◆◆▲▲ 0.0003±0.0001■■■□□□▲▲▲△△△◆◆◆ 0.0003±0.0001■■■□□□△△△◆◆◆▲▲ |
Annotate: ■ ■ ■ organizes relatively P＜0.001 with normal rutting period
compares P＜0.001 with normal diestrus group
▲ ▲ compare P＜0.01 rutting period with sham operated rats; ▲ ▲ ▲ compares P＜0.001 with sham-operation group in rutting period
△ △ △ and sham-operation diestrus group compare, P＜0.001
* * and castration normal saline group compare, P＜0.001
◆ ◆ ◆ compare P＜0.001 with the premarin group
2, uterus pathological section result
Low power lens (10 * 10) is observed down the uterus pathological section, selects the thickest, the thinnest and intermediate gauge three places of every routine specimen inner membrance to take pictures, and behind software measurement, calculates the meansigma methods of inner film thickness, covering epithelium thickness, flesh layer thickness.
The high low dosage of table 15 medicine of the present invention is to castrated rats endometrium thickness and the in utero influence of film covering epithelium
| Group | The example number | Inner film thickness (μ m) | Covering epithelium thickness (μ m) |
| A high left side, normal sham-operation sham-operation in rutting period of normal dioestrus in a rutting period dioestrus castration normal saline premarin left side is low right high right low | 10 10 7 10 8 11 6 9 6 9 | 7.72±1.38*** 6.22±1.61** 10.60±2.54 6.17±1.41** 2.65±0.40◆◆◆■■□□△△ 8.58±2.24*** 2.99±0.69■■■◆◆◆△△□▲ 2.79±0.58■■■◆◆◆□□△△▲ 2.75±0.63■■■◆◆◆□□△△▲ 1.82±0.35■■■◆◆◆△△△□□▲ | 0.20±0.07 0.17±0.05 0.27±0.05* 0.20±0.05* 0.11±0.04◆◆◆▲△ 0.28±0.04*** 0.09±0.01◆◆◆△△▲ 0.10±0.03◆◆◆△△▲ 0.10±0.02◆◆◆△△▲ 0.08±0.02◆◆◆△△■□▲ |
Annotate: ■ organizes relatively ■ P＜0.05 ■ ■ P＜0.01 ■ ■ ■ P＜0.001 with normal rutting period
compares P＜0.05 P＜0.01 with normal diestrus group
▲ compare ▲ P＜0.05 rutting period with sham operated rats
△ and sham-operation diestrus group compare, △ P＜0.05 △ △ P＜0.01 △ △ △ P＜0.001
* compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with castration normal saline group
◆ compare with the premarin group, ◆ ◆ ◆ P＜0.001
Table 15 prompting: high low dose group of medicine of the present invention and castration normal saline group compare, endometrium thickness and inner membrance covering epithelium thickness there was no significant difference (P＞0.05).
3, the influence of medicine myometrium thickness of the present invention
The high low dosage of table 16 medicine of the present invention is to the influence of castrated rats myometrium thickness
| Group | The example number | Flesh layer thickness (μ m) |
| A high left side, moving sham-operation in the rutting period dioestrus castration normal saline premarin of normal normal dioestrus sham-operation in a rutting period left side is low right high right low | 10 10 7 10 8 11 6 9 6 9 | 2.20±0.59** 2.10±0.46** 2.41±0.34*** 2.14±0.59* 0.95±0.31▲▲▲◆◆◆■■□□△ 2.78±0.54*** 1.09±0.39◆◆◆▲ 1.09±0.30▲▲▲◆◆◆□□■△ 0.84±0.25▲▲▲◆◆◆■■□□△△ 0.67±0.17▲▲▲◆◆◆□□□■■△△ |
Annotate: ■ organizes relatively ■ P＜0.05 ■ ■ P＜0.01 with normal rutting period
compares P＜0.01, P＜0.001 with normal diestrus group
▲ compare ▲ P＜0.05 rutting period with sham operated rats
△ and sham-operation diestrus group compare, △ P＜0.05 △ △ P＜0.01
* compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with castration normal saline group
◆ compare with the premarin group, ◆ ◆ ◆ P＜0.001
Table 16 prompting: high low dose group of medicine of the present invention and castration normal saline group compare, myometrium thickness there was no significant difference (P＞0.05).
4, medicine of the present invention is to the influence of castrated rats endometrial gland diameter, internal diameter, glandular epithelium height
Observe the uterus pathological section with high power lens (40 * 10), three of the inner membrance bodies of gland that each specimen is selected to be of moderate size are taken pictures the back with software measurement body of gland diameter, internal diameter, glandular epithelium height, calculate meansigma methods; Each specimen is calculated the body of gland quantity in 5 visuals field of low power lens (10 * 10)
The high low dosage of table 17 medicine of the present invention is to the influence of castrated rats endometrial gland diameter, internal diameter, glandular epithelium height
| Group | The example number | Body of gland diameter (μ m) | Body of gland internal diameter (μ m) | Glandular epithelium height (μ m) |
| A high left side, normal sham-operation sham-operation in rutting period of normal dioestrus in a rutting period dioestrus castration normal saline premarin left side is low right high right low | 10 10 7 10 8 11 6 9 6 9 | 0.71±0.14* 0.60±0.13* 0.81±0.14** 0.69±0.09** 0.42±0.08△△◆◆■□ 0.93±0.26** 0.54±0.09 0.50±0.12◆ 0.40±0.06△△△■■◆◆□ 0.40±0.06△△△■■◆◆□ | 0.43±0.13 0.40±0.10 0.44±0.21 0.41±0.06** 0.24±0.06◆◆△△ 0.69±0.22** 0.35±0.133 0.25±0.07△△◆◆ 0.24±0.07◆◆ 0.24±0.07△△◆◆ | 0.14±0.03 0.12±0.05 0.13±0.02 0.11±0.04 0.08±0.01 0.15±0.06 0.08±0.02 0.09±0.02 0.08±0.03 0.08±0.01 |
Annotate: ■ organizes relatively ■ P＜0.05 ■ ■ P＜0.01 with normal rutting period
compares P＜0.05 with normal diestrus group
▲ compare ▲ P＜0.05 rutting period with sham operated rats
△ and sham-operation diestrus group compare, △ △ P＜0.01, △ △ △ P＜0.001
* compare * P＜0.05 * * P＜0.01 with castration normal saline group
◆ compare with the premarin group, ◆ P＜0.05 ◆ ◆ P＜0.01
Table 17 prompting: high low dose group of medicine of the present invention and castration normal saline group compare, endometrial gland diameter, internal diameter, glandular epithelium height there was no significant difference (P＞0.05).
5, medicine of the present invention is to the influence of castrated rats uterus body of gland number
The high low dosage of table 18 medicine of the present invention is to the influence of castrated rats uterus body of gland number
| Group | The example number | The body of gland number |
| A high left side, moving sham-operation in the rutting period dioestrus castration normal saline premarin of normal normal dioestrus sham-operation in a rutting period left side is low right high right low | 10 10 7 10 8 11 6 9 6 9 | 39.20±11.06* 32.10±8.96* 52.86±13.06* 27.50±9.51 14.00±4.90◆◆◆■□▲ 35.09±6.98*** 13.00±4.76◆◆◆■■□▲ 14.22±4.41◆◆◆■□▲ 11.83±5.12◆◆◆■■□▲ 12.22±4.32◆◆◆■■□□▲ |
Annotate: ■ organizes relatively ■ P＜0.05 ■ ■ P＜0.01 with normal rutting period
compares with normal diestrus group, P＜0.05, and P＜0.01,
▲ compare ▲ P＜0.05 rutting period with sham operated rats
* compare * P＜0.05 * * * P＜0.001 with castration normal saline group
◆ compare with the premarin group, ◆ ◆ ◆ P＜0.001
Table 18 prompting: high low dose group of medicine of the present invention and castration normal saline group compare, uterus body of gland number there was no significant difference (P＞0.05).
6, medicine of the present invention is to the influence of vagina weight in wet base and vagina organ index
Table 19 medicine high dose of the present invention is to the influence of rat vagina weight in wet base and vagina organ index
| Group | The example number | Weight in wet base (g) | The vagina organ index |
| Normal sham-operation sham-operation in rutting period of normal dioestrus in a rutting period dioestrus castration normal saline premarin left side is high right high | 10 10 7 10 8 11 6 6 | 0.34±0.04*** 0.28±0.07*** 0.34±0.06*** 0.29±0.05*** 0.15±0.03■■■□□□▲▲▲△△△◆◆◆ 0.28±0.05*** 0.14±0.02■■■□□□▲▲▲△△△◆◆◆ 0.14±0.04■■■□□□▲▲▲△△△◆◆◆ | 0.0013±0.0002***□□△ 0.0010±0.0003***■■▲▲ 0.0012±0.0003***□□ 0.0010±0.0002***■ 0.0005±0.0001■■■□□□▲▲▲△△△◆◆◆ 0.0011±0.0002*** 0.0004±0.0001■■■□□□▲▲▲△△△◆◆◆ 0.0004±0.0001■■■□□□▲▲▲△△△◆◆◆ |
Annotate: ■ organizes relatively ■ P＜0.05 ■ ■ P＜0.01 ■ ■ ■ P＜0.001 with normal rutting period
compares with normal diestrus group, P＜0.05, and P＜0.01,
▲ compare ▲ P＜0.05 rutting period with sham operated rats
△ and sham operated rats diestrus compare, △ P＜0.05 △ △ △ P＜0.001
* compare * * * P＜0.001 with castration normal saline group
◆ compare with the premarin group, ◆ ◆ ◆ P＜0.001
Table 19 prompting: medicine high dose group of the present invention and castration normal saline group compare, vagina weight in wet base, organ index there was no significant difference (P＞0.05).
Above-mentioned safety experiment proves, the premarin group all has a significant effect to uterus weight in wet base, uterus organ index, endometrium thickness and inner membrance covering epithelium thickness, endometrial gland diameter, internal diameter, glandular epithelium height, vagina weight in wet base, organ index etc., and prolonged and repeated use has certain side effect.And medicine of the present invention is only by increasing vagina pleat number and vagina lamina propria blood vessel number, and organize the activity of aromatase to increase estrogen synthesis outward to reach that to delay vagina wither by strengthening gonad, the purpose of prevention and treatment senile vaginitis, simultaneously to not influence of other tissue relevant with estrogen, the with strong points of chemoprophylaxis of the present invention and treatment is described, compares, can not have side effects other tissue with controversies in hormone replacement in the elderly, safety is good, can life-time service.
Experimental example 7 clinical drug experiments of the present invention
One, diagnostic criteria:
Medical history women is menopause, or bilateral ovaries is excised.
The symptom vaginal secretions increases, and is thin, faint yellow, can be with sexual anhedonia, and severe patient is blood sample, purulence.
Pruritus vulvae, causalgia, part patient's frequent micturition, dysurea.
The atrophy of gynecologial examination vaginal mucosa, pleat disappear, mucosa hyperemia, redness, visible petechia, the visible ulcer of severe patient.
Lab testing vaginal secretions plate coating checking, microscopically is seen a large amount of basal layer cells and leukocyte, no infusorian, no candidiasis, clues cell is less than 20%, and cervical scraping smear Pasteur is below 2 grades, and vaginal exfoliated inspection prompting estrogen level is low, serum FSH, the LH big menopause level that significantly raises, E2 value are significantly low.
Curative effect assessment pruritus vulvae, causalgia disappear, and vaginal secretions reduces, and check that the hyperemia of skin of vulva and vaginal mucosa disappears for curing.
Because of the ovarian function decline, decrease in estrogen, vaginal epithelial cell gathers glycogen to be reduced, and old people's vagina causes the local resistance of vagina and descends, so senile vaginitis is common.
The diagnosis of senile vaginitis generally is not difficult, but should get rid of other diseases, should differentiate mutually with uterine malignant tumour (carcinoma of endometrium, cervical cancer) and cancer of vagina especially sanguinous leukorrhea.
Senile vaginitis is through estrin treatment, but drug withdrawal after the elimination secondary infection, vaginal mucosa is got back to atrophy and is not had the infection state, and only a few need be interrupted treatment repeatedly.
The visible pudendum flushing of diagnosis toposcopy, moistening, vaginal wall hyperemia is dispersed in the petechia, and fornix and cervix uteri are the most obvious, and diagnosis generally is not difficult.Should get vaginal secretions and look into pathogen such as infusorian, mycete.Temporary dwelling palace neck or endometrial biopsy in case of necessity.
Two, conclusion
Medicine composite for curing senile vaginitis, especially normal type of the present invention or be lower than the senile vaginitis of normal type have drug effect preferably.Wherein embodiment 1-6 all can reach drug effect preferably.Embodiment 3-6 compares with embodiment 1,2, though on the raw material consumption, be less than embodiment 1,2, but the effect experiment at the treatment senile vaginitis shows, brought into play identical effect, therefore, Radix Rehmanniae Preparata, Fructus Corni, Rhizoma Dioscoreae, Fructus Lycii, Semen Cuscutae, Colla cornus cervi six medicaments are for treating the core compatibility of senile vaginitis in the raw material of the present invention, and its selection and concrete consumption are also non-obvious for a person skilled in the art.
List of references:
[1]Simpson?ER，Zhao?Y，Agarwal?VR，Michael?MD，Bulun?SE，et?al.Aromataseexpression?in?health?and?disease.Rec?Prog?Horm?Res.1997.52：185-214
[2]Simpson?E，Rubin?G，Clyne?C，et?al.The?role?of?local?estroge?n-biosynthesisin?males?and?females.Trends?Endocrinol?Metab?2000.11(5)：184-188
[3]Labrie?F，Belanger?A，Cusan?L，Gomez?J?L，Candas?B.Marked?decline?in?serumconcentrations?of?adrenal?C19?sex?steroid?precursors?and?conjugated?androgenmetabolites?during?aging.J?Clin?Endocrinol?Metab.1997，28(8)2386～2402
[4]Holst?D，Grimaldi?PA.New?factors?in?the?regulation?of?adipose?differentiationand?metabolism.Curr?Obin?Lipidol.2002，13：241-245
[5]Greenberg?AS，McDaniel?MI.Identifying?the?links?between?obesity，insulinresistance?and?beta-cell?function：Potential?role?of?adipcyte-derived?cytokinesin?the?pathogenesis?type?2?diabetes.Eur?J?Clin?Invest.2002，13：24-34
[6] big Seeley husband etc. estrogen deficiency and bone metabolism [J] Japan medical science is introduced .1986 (6): 272
[7]Meldrum?DR，Davidson?BJ，Tataryn?IV，Judd?HL.Changes?in?circulating?steroidswith?aging?in?postmenopausal?women.Obstet?Gynecol.1981，57：624
[8]McTernan?PG，Anwar?A，Eggo?M?C，et?al.Gender?differences?in?the?regulationof?P450?aromatase?expression?and?activity?in?human?adipose?tissue.Iht?J?Obes?RelatMetab?Disord.2000，2(7)：875-878
[9]Wing?R?R，Matthews?K?A，Kuller?L?H，et?al.Weight?Gain?at?the?Time?of?Menopause.Arch?Intern?Med.1991，151：97
[10]Carey?DG，Jenkins?AB，Campell?LV，et?al.Abdominal?fat?and?insulin?resistancein?normal?and?overweight?women：direct?measures?reveal?a?strong?relationship?insubjects?at?both?low?and?high?risk?of?NIDDM[J].Diabetes.1996，45：633-638
[11] Lu Meifang, Yuan Ying, etc. women's stomach fat is organized research [J] the Tianjin medicine .2004 that aromatase mRNA is expressed after menopause, and 10 (10): 610-612
[12] Warming L...Am J. in healthy menopausal women interior fat to endometrium thickness and sclerotin than periphery fat more important [J] .Obstet Gynecol.2003,188 (2): 349-353
[13] Zhu Xiaohui, Wang Jun, etc. estrogen intervention influences abdominal cavity fat experimental study of accumulation [J]. Chinese clinical pharmacology and treatment .2003,8 (6): 669-672
[14]Witteman?JC，Grobbee?DE，Kok?FJ，et?al.Increased?risk?of?atherosclerosis?inwomen?after?the?menopause[J].Br?Med?J1989，298：642-644
[15]Belanger?C，Luu-TheV，Dupont?P，et al.Adipose?tissueintracrinology：potential?importance?of?local?androgen/estrogen?metabolism?in?theregulation?of?adiposity[J].Horm?Metab?Res?2002，34：737-745
[16] Liu Yi, etc. long-term hormone replacement therapy is to influence [J] .G.Perron of postmenopausal women's body composition and the distribution of body fat, the journal .1999 of Xinjiang Medicine University, 22 (1): 9-10
[17]Haarbo?J，Marslew?U，Gotfredsen?A，et?al.Postmenopausal?hormone?replacementtherapy?prevents?central?distribution?of?body?fot?after?menopause.Metabolism.1991，40(12)：132-133
[18]Green?H，Kehinde?O.Spontaneous?heritable?changes?leading?to?increasedadipocyte?conversion?in?3T3?cells[J].Cell.1976，7(1)：105-113
[19]Longcope?C，Pratt?JH，Schneider?SH，et?al.Aromatization?of?androgens?bymuscle?and?adipose?tissue?in?vivo.J?Clin?Endocrinol?Metab.1978；46：146
[20]Caroline?J.Speed，Evan?R.Inhibition?of?Aromatase?Transcription?Via?PromoterII?by?Short?Heterodimer?Partner?in?Human?Preadipocytes?Agnes?Kovacic.MolecularEndocrinology?18(1)：252-259
[21]Jianfeng?Zhou，Bilgin?Gurates.Malignant?Breast?Epithelial?Cells?StimulateAromatase?Expression?via?Promoter?II?in?Human?Adipose?Fibroblasts?CancerResearch.2001?March?1，61，2328-2334
[22]Clyne?DC，Speed?CJ，Zhou?J，et?al.Liver?receptor?homologue-1(LRH-1)regulatesexpression?of?aromatase?in?preadipocytes?[J].JBio?Chem，2002，277(23)：20591-20597
[23] Li Yikui. some problems [J] of Chinese medicine serum pharmacological experimental technique. new Chinese medicine and clinical pharmacology.1999，10(2)：95.
Claims (11)
1. contain pharmaceutical composition that the following weight proportion raw material is prepared from and delay purposes in the wither medicine of vagina: Radix Rehmanniae Preparata 18-30 part, Fructus Corni 9-12 part, Rhizoma Dioscoreae 8-16 part, Fructus Lycii 9-12 part, Semen Cuscutae 8-16 part, Colla cornus cervi 8-16 part in preparation.
2. purposes according to claim 1 is characterized in that: described medicine is the medicine that increases the confession of vagina blood.
3. purposes according to claim 1 and 2 is characterized in that: described medicine is to strengthen the medicine that gonad is organized activity of aromatizing enzyme outward.
4. purposes according to claim 1 and 2 is characterized in that: described medicine is that prevention is or/and the medicine of treatment senile vaginitis.
5. purposes according to claim 4 is characterized in that: described senile vaginitis, its patient is normal type or the patient who is lower than normal type.
6. purposes according to claim 1 and 2 is characterized in that: described pharmaceutical composition is the medicament that is prepared from by the following weight proportion raw material:
24 parts in Radix Rehmanniae Preparata, Fructus Corni 9-12 part, 12 parts of Rhizoma Dioscoreaes, Fructus Lycii 9-12 part, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis.
7. the pharmaceutical composition that is prepared from by the following weight proportion raw material delays purposes in the wither medicine of vagina in preparation:
24 parts in Radix Rehmanniae Preparata, Fructus Corni 9-12 part, 12 parts of Rhizoma Dioscoreaes, Fructus Lycii 9-12 part, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis, 9 parts of Radix Cyathulaes, 12 parts of Colla Plastri Testudiniss.
8. purposes according to claim 7 is characterized in that: described pharmaceutical composition is to be prepared from by the following weight proportion raw material:
24 parts in Radix Rehmanniae Preparata, 12 parts of Fructus Corni, 12 parts of Rhizoma Dioscoreaes, 12 parts of Fructus Lycii, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis, 9 parts of Radix Cyathulaes, 12 parts of Colla Plastri Testudiniss.
9. the pharmaceutical composition that is prepared from by the following weight proportion raw material delays purposes in the wither medicine of vagina in preparation:
24 parts in Radix Rehmanniae Preparata, Fructus Corni 9-12 part, 12 parts of Rhizoma Dioscoreaes, Fructus Lycii 9-12 part, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis, 12 parts of the Cortexs Eucommiae, 6 parts of Cortex Cinnamomis, 9 parts of Radix Angelicae Sinensis, 6 parts of Radix Aconiti Lateralis Preparata.
10. purposes according to claim 9 is characterized in that: described pharmaceutical composition is to be prepared from by the following weight proportion raw material:
24 parts in Radix Rehmanniae Preparata, 9 parts of Fructus Corni, 12 parts of Rhizoma Dioscoreaes, 9 parts of Fructus Lycii, 12 parts of Semen Cuscutae, 12 parts of Colla cornus cervis, 12 parts of the Cortexs Eucommiae, 6 parts of Cortex Cinnamomis, 9 parts of Radix Angelicae Sinensis, 6 parts of Radix Aconiti Lateralis Preparata.
11. purposes according to claim 6 is characterized in that: described medicament is pill, capsule, tablet, oral liquid.
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Non-Patent Citations (8)
| Title |
|---|
| 刘兰芬等.左归丸加减治疗萎缩性外阴炎15例.中医药研究 3.1994,(3),29. |
| 刘兰芬等.左归丸加减治疗萎缩性外阴炎15例.中医药研究 3.1994,(3),29. * |
| 刘春煦.左归丸加味治疗席汉氏综合征.甘肃中医11 2.1998,11(2),33. |
| 刘春煦.左归丸加味治疗席汉氏综合征.甘肃中医11 2.1998,11(2),33. * |
| 李瀚旻.左归丸现代临床应用和实验研究进展.中国实验方剂学杂志10 1.2004,10(1),58-60，65. |
| 李瀚旻.左归丸现代临床应用和实验研究进展.中国实验方剂学杂志10 1.2004,10(1),58-60,65. * |
| 肖钢.左归丸加减治疗萎缩性外阴炎25例.新中医 1.1987,(1),38. |
| 肖钢.左归丸加减治疗萎缩性外阴炎25例.新中医 1.1987,(1),38. * |
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