CN101766743A - Drug combination for treating permenstrual syndrome - Google Patents
Drug combination for treating permenstrual syndrome Download PDFInfo
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Abstract
The invention discloses a drug combination for permenstrual syndrome, comprising the following crude drugs by weight parts: 30-60 parts of radix bupleuri, 30-60 parts of rhizoma cyperi, 30-60 parts of pericarpium citri reticulatae viride, 30-60 parts of root of common peony, 50-80 parts of the root of red-rooted salvia, 50-80 parts of the seed of cowherb, 50-80 parts of caulis spatholobi, 160-320 parts of oyster, 50-80 parts of seaweed, 50-80 parts of kelp, 50-80 parts of herba epimedii and 50-80 parts of the seed of Chinese dodder. Twelve Chinese herbal medicines in the invention acts on mutually, so as to have expectant good synergistic effect of the designed formula; the synergistic effect can effectively relieve and eliminate symptoms such as headache, dizziness, breast swelling, a little pain, falling into a flutter, upset insomnia, mental tension, melancholy, puffy face and the like which are caused by menstrual periodic change; the drug combination has good effect on treating permenstrual syndrome.
Description
Technical field
The present invention relates to pharmaceutical product, specifically by vegetable drug pharmaceutical composition formulated, that be applicable to premenstrual syndrome.
Background technology
Premenstrual tension syndrome is that every lunar periodicity disturbs the able-bodied common disease of women, belongs to the category of menstruation disease.Its clinical manifestation variation, and weight differs.This disease is generally maximum with the women of 30-40 between year, and sees with city and mental work women more.The harm of premenstrual tension syndrome not only is patient's self sensation, and the consequence that is produced under some situation if do not add notes or do not give suitable treatment, then may increase the weight of or brings out unusual breeding a tragedy on more original spiritual psychology or the health because of compelling sex behaviors such as its irritability, depressions.
At present, at the treatment of premenstrual tension syndrome, clinical generally is to learn characteristics according to patient Pathophysiology and mental community at that time, adopts the individualized treatment scheme, to reach best effects.Therapeutic scheme is divided into non-drug therapy and Drug therapy.Non-drug therapy comprises psychological counseling, sports and dietary adjustments etc., and its effect is uncertain.Drug therapy mainly contains three classes: the first kind is for taking 5-hydroxy tryptamine reuptake inhibitor (SSRI), as fluoxetine.Curative effect that there are some researches show the premenstrual tension syndrome that this class Drug therapy of employing is serious is higher 7 times than placebo group.Second class is to take the medicine that suppresses ovulation, as GnRH-a, danazol etc.This class drug main will be by suppressing ovulation, thereby change endocrine environment in the body, and symptoms such as the melancholy that alleviates premenstrual tension syndrome, distending pain of the breast are had certain effect.The 3rd class is symptomatic treatment, promptly according to the concrete symptom that patient showed, takes spironolactone targetedly, smells latent stopping or medicine such as vitamin B6.Because usually there is serious adverse effects in chemical synthetic drug, therefore, many clinicists do not advocate that generally the premenstrual tension syndrome patient takes the pharmaceutical chemistry synthetic drug.Also there is the doctor to think that premenstrual tension syndrome and estrogen, progestogen are out of proportion relevant, therefore advocate to adopt hormone therapy, but its effect is not satisfactory.
Chinese medicine it is generally acknowledged that this disease mainly is because due to congestion of the liver addiction or the kidney spleen deficiency, so many opinion determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs.Clinical also have adopt Chinese patent drugs for treatment premenstrual tension syndrome with dispersing the stagnated live-QI to relieve the stagnation of QI function.As ease pill mainly is to be used for diseases such as caused hypochondriac pain a little less than stagnation of liver-QI, blood deficiency, the spleen, melancholia, low grade fever, nodules of the breast.Clinically treat premenstrual tension syndrome (PMS), also obtained curative effect preferably with it.But, clinically still need more, better medicament and can select for people.
Summary of the invention
Purpose of the present invention just provides pharmaceutical composition a kind of determined curative effect, that can be used for treating premenstrual tension syndrome.
The object of the present invention is achieved like this:
The pharmaceutical composition of treatment premenstrual syndrome provided by the present invention comprises the crude drug of following weight part ratio:
Radix Bupleuri 30-60 part, Rhizoma Cyperi 30-60 part, Pericarpium Citri Reticulatae Viride 30-60 part, Radix Paeoniae Rubra 30-60 part, Radix Salviae Miltiorrhizae 50-80 part, Semen Vaccariae 50-80 part, Caulis Spatholobi 50-80 part, Concha Ostreae 160-320 part, Sargassum 50-80 part, Thallus Laminariae (Thallus Eckloniae) 50-80 part, Herba Epimedii 50-80 part, Semen Cuscutae 50-80 part.
For further strengthening effect of the present invention, in drug component, can increase some regulating menstruation Chinese medicines, as Radix Angelicae Sinensis, Flos Carthami etc.
The preferred crude drug weight part ratio of the present invention is:
Radix Bupleuri 48-56 part, Rhizoma Cyperi 48-56 part, Pericarpium Citri Reticulatae Viride 48-56 part, Radix Paeoniae Rubra 48-56 part, Radix Salviae Miltiorrhizae 64-74 part, Semen Vaccariae 64-74 part, Caulis Spatholobi 79-80 part, Concha Ostreae 160-180 part, Sargassum 79-80 part, Thallus Laminariae (Thallus Eckloniae) 79-80 part, Herba Epimedii 79-80 part, Semen Cuscutae 79-80 part.
Pharmaceutical composition of the present invention can extract, concentrate it according to the Chinese herbal medicine extracting technology of routine.Again according to the conventional formulation requirement, the medicinal adjuvant (as excipient, disintegrating agent, adhesive, lubricant, antioxidant, coating materials, coloring agent, aromatic, surfactant etc.) of extract with routine mixed, make oral formulations or ejection preparations such as injection, infusion solution such as granule, capsule, tablet, oral liquid.
When the present invention is used for the treatment of premenstrual tension syndrome, but oral administration or without oral administration.Dosage is also different different because of the weight of dosage form difference and conditions of patients.Concerning the adult, dose for oral use, every day is more suitable in crude drug amount 30～200g.Intramuscular injection or intravenous injection medication, every day is more suitable in crude drug amount 5～100g.In clinical practice, should respect doctor's advice.
The present invention provides a kind of extraction preparation method at this:
(1) gets above-mentioned ten raw medicinal herbs simply except that Semen Vaccariae, decoct with water twice.2 hours for the first time, 1.5 hours for the second time, merge decoction liquor, filter filtrate for later use;
(2) Semen Vaccariae is cleaned, added water, decoct twice, 1.5 hours for the first time, 1 hour for the second time, merge decoction liquor, filter, filtrate is concentrated into density and is about 1.1 (70～80 ℃), room temperature to be chilled to, the ethanol that adds equivalent makes precipitation, filters, and is standby behind the filtrate recycling ethanol;
(3) filtrate in (1) (2) is merged, be concentrated in right amount, add suitable amount of sucrose and dextrin, make granule.
When the present invention designs at medicament composing prescription, with reference to the multi-pathogenesis hypothesis of the relevant premenstrual tension syndrome of western medicine and Chinese medicine many pathogenesis theory through all cards of row.Determine the leading theory of medicament research and development, promptly treated premenstrual tension syndrome and not only will consider this pathogenetic external factor, more should probe into this pathogenetic internal environment.So should be both after medicine 5 usefulness can adjustment women premenstruum intravital estrogen change, again can be soothing the liver, resolving depression, circulation of qi promoting, blood stasis dispelling, eliminate the sense of the discomfort that the women caused because of the physiological period variation.
12 selected flavor Chinese herbal medicine of the present invention interact, and have produced the good synergism of prescription expected design thus.The headache that the women is caused because of menstrual cycle changes can effectively be alleviated, be eliminated to medicine of the present invention, dizziness, symptom such as breast expands, or feels pain slightly, and is in a disturbed state of mind, and vexed insomnia, psychentonia, melancholy, face are impractical.It is used for the treatment of premenstrual syndrome and has good curative effect.
Beneficial effect of the present invention has obtained checking by following experiment.
Medicine of the present invention abbreviates newborn disease spirit as in following experiment.
Experiment one
With the animal model of exogenous estrogen (estradiol benzoate) subcutaneous injection, and treat with newborn disease spirit with the class premenstrual tension syndrome disease that causes high estrogen or high estrogen/progesterone ratio.
1 laboratory animal:
The SD rat, all female, totally 66, body weight 190～220 gram, at 3～4 monthly ages, effluent north medical university animal center provides, the quality certification number: DK0411-0031.
2 experimental drugs
2.1 estradiol benzoate injection, 1ml/ props up, and every ml includes 1mg, Shanghai General Pharmaceutical Co., ltd., lot number 06010216.
2.2 1,2-propylene glycol, Chengdu chemical reagent factory, lot number 20060607.
2.3 spironolactone (spironolactone), 20mg/ sheet, Hangzhou Minsheng Pharmaceutical Group Co, lot number 061268; Irritate before the stomach that to be mixed with the 0.6mg/ml suspension with distilled water standby.
2.4 newborn disease Lingshui Spring decoct (made according to embodiment 1), 1ml is equivalent to the 0.75g crude drug, and sterilization packing cold preservation is standby.
3 main agents
3.1 estradiol (E
2) radioimmunological kit: provide lot number KE2D10117 by Depew, Tianjin (DPC) company.
3.2 progesterone (P) radioimmunological kit: provide lot number KPGD10089 by Depew, Tianjin (DPC) company.
3.3 prolactin antagonist radioimmunological kit: provide lot number KPRD10115 by Depew, Tianjin (DPC) company.
3.4 testosterone (T) radioimmunological kit: provide lot number KTTD10116 by Depew, Tianjin (DPC) company.
3.5 (radioimmunological kit of β-EP): Creat Company provides lot number 060315 to beta-endorphin by the sea, Tianjin.
3.6 standard dopamine (DA): provide by FLUKE company.
3.7 standard norepinephrine (NE): provide by SEPVA company.
3.8 standard 5-hydroxy tryptamine (5-HT): by the chemical reagent purchasing station import packing of China Drug Co. Shanghai.
3.9 estrogen receptor (ER) mouse monoelonal Antibody is provided lot number Lot D2403 by NEOMARKERS company.
3.10 the two anti-corresponding reagent boxes that reach are provided by Beijing Zhong Shan biotech company.
4 main test instrunments
4.1 ordinary optical microscope.
4.2 electronic analytical balance (the German SARTORDJS BP61 of company).
4.3FJ-2008P automatic Y immunity enumerator (Plant No. 262).
4.4960CRT spectrofluorophotometer (Shanghai precision instrument scientific instrument company limited).
4.5BX50-20LYMPUS optical microscope.
4.6H-600IV type transmission electron microscope (HIT).
5 experimental techniques
5.1 laboratory animal grouping
40 rats are divided into 4 groups at random, 10 every group: blank group, model group, positive drug group (spironolactone group), newborn disease spirit group.
Each group all gives identical particle feedstuff (effluent north medical university animal center provides) in whole experiment, the drink tap water is freely ingested, the open-shelf sub-cage rearing, and 5～6 in every cage, natural lighting and every day regularly clean, and adaptability begins experiment after feeding a week.20～30 ℃ of feeding environment room temperatures, relative humidity 65～75%.
5.2 dosage and method
Blank group: morning every day, the subcutaneous injection sterilization 1,2-propylene glycol injection, and 0.05ml/ time, gavage distilled water afternoon, 1ml/100g/ time, continuous 7 days.
Model group: the morning every day subcutaneous injection estradiol benzoate injection, 0.5ml/50ug/ time, gavage distilled water afternoon, 1ml/100g/ time, continuous 7 days.
The spironolactone group: morning every day, the subcutaneous injection estradiol benzoate injection was 0.05ml/50ug/ time, gavaged the spironolactone suspension afternoon, and 1ml/100g/ time, adult dosage 40mg, by people Mus body surface area conversion dosage, 6 times of the dosage of being equivalent to be grown up, continuous 7 days;
Breast disease spirit group: morning every day, the subcutaneous injection estradiol benzoate injection was 0.05ml/50ug/ time, gavaged newborn disease Lingshui Spring decoct afternoon, 1ml/100g/ time, pressed people Mus body surface area and converted dosage, 6 times of the dosage of being equivalent to be grown up, continuous 7 days;
5.3 laboratory observation index and method
5.3.1 overview
After the grouping, begin to observe and respectively organize situations such as rat behavior, sign, body weight, and the variation of making before and after the administration contrasts.
5.3.2 the observation of vagina epithelium exfoliative cyte cardiac index,contrast index,cornification index
Administration the last week, each organizes rat by only making vagina epithelium exfoliative cyte smear, once a day, and continuous 7 days; Respectively organize modeling in morning every day after the administration, the perfusion in afternoon, and get the vagina epithelium exfoliative cyte every day, continuous 7 days.
Method: make very thin cotton swab, soak with normal saline, inserting the rat vagina clockwise direction rotates a circle, get exfoliative cyte, the cotton swab inhour smear that rotates a circle on the cleaning microscope slide of will sampling, smear is put into immediately and is done Yihong dyeing after 95% ethanol liquid is fixed 5 minutes, observes ripe keratinocyte percentage ratio under ordinary optical microscope, with the shared percentage calculation keratinocyte of ripe Keratinocytic number index in per 200 exfoliative cyte; Statistical software calculates with the input of (back) before every rat experiment keratinocyte exponential average of 7 days.
5.3.3 rat blood serum E
2, P, T, PRL put inspection-free survey
10 sacrifice of animal of every group selection after 24 hours after the last administration, femoral artery is got blood, separation of serum, it is to be measured to be stored in cryogenic refrigerator (20 ℃), detection method is undertaken by the appended explanation of test kit, detection site is carried out at Shijiazhuang safety hospital radiological department, adopts the automatic Y immunity of FJ-2008P enumerator to measure.
5.3.4 the rat hypothalamus estrogen receptor is measured
After the rat femoral blood sampling, broken end is opened cranium and is got brain rapidly, separate hypothalamus (cut specimen front 2mm to the optic chiasma, the back is to mammillary body, side from the hypothalamus crackle to from the dark tissue of bottom surface 3mm), and be upper and lower two halves from middle 1/2 lateral separation, take off half part and put into 10% formalin and fix, step by step dehydration of alcohol, dimethylbenzene is transparent, waxdip, paraffin embedding, conventional section 4um, immunohistochemical staining (SP method) is carried out in HE dyeing.The BX50-OXYMPUS observation by light microscope coloration result that provides by Shijiazhuang safety hospital pathology department; Adopt the Mias-2000 image analysis system to carry out result treatment.
5.3.5 rat hypothalamus beta-endorphin assay
Get the about 25mg ± 2mg of first hypothalamus, putting 100 ℃ of normal saline took out after 5 minutes, after placing 1ml to contain the abundant acidify of glass homogenate bottle of 1 normal hydrochloric acid solution, with the neutralization of 1 Equivalent Hydrogen sodium oxide, put on the high speed centrifuge with 3000 rev/mins, after centrifugal 10 minutes, get supernatant, be stored in-20 ℃ of refrigerators according to putting the operational approach of exempting from the medicine box description, measure beta-endorphin content, detect by Shijiazhuang safety hospital radiological department with the automatic Y immunity of FJ-2008P enumerator.
5.3.6 rat brain stem neurotransmitter is measured
Separate brain stem again after the rat broken end is peeled off hypothalamus, promptly midbrain, brains are freezing immediately.Tissue weighed put into homogenizer, add a small amount of acidify n-butyl alcohol, in ice bath, prepare homogenate; Homogenate is transferred to graduated centrifuge tube, mends to 4ml with the acidify n-butyl alcohol; Vibration, centrifugal 5 minutes, to get supernatant 2.5ml and put into another centrifuge tube, every pipe adds normal heptane 5ml and 0.1M HD1.2ml, vibration, centrifugal 5 minutes, this liquid was divided into biphase, gets 0.5ml respectively from aqueous phase and (be designated as 1 group and 2 groups) in two test tubes.
1 group: add 1/15M phosphate buffer 1.7ml, add iodine reagent 0.1ml again after, leave standstill 2min; Add alkaline sodium sulfite 0.5ml, leave standstill 2min; Add HAC 0.6ml, behind the boiling water bath 2ml, the methylepinephrine fluorescence intensity is surveyed in the cold water cooling at the 480nm/365nm place; Add 45% phosphoric acid 0.1ml again, boiling water bath 15min after the cold water cooling, measures the dopamine fluorescence intensity at the 379nm/310nm place.
2 groups: add 0.5% cysteine and 0.004%OPT 3M, boiling water bath after the cold water cooling, was measured the 5-hydroxy tryptamine fluorescence intensity after 10 minutes at the 480nm/365nm place.
Above index is measured in biochemical teaching and research room of Hebei Medical University.
5.3.7 the statistical disposition of experimental data:
All data all adopt SPSS (11.0) statistical package to carry out, and calibration is relatively adopted LSD and S-N-K with one-way ANOAY variance analysis between group.
6 experimental results:
6.1 respectively organize the variation of rat behavior sign after the medication:
It is normal respectively to organize mice develop before the experiment, and action vivaciously freely, and is dense glossy by hair, and the scarlet spiritedness of eyes is movable fast quick, to external irritant reaction sensitivity, is the defence attitude.
Compare no significant change before testing back blank group mice and testing; Estrogen group mice is owed gloss by hair, spirit still can, loose and watery stool is soft, and external irritant is shown indifferent slightly, is and hides attitude.Other groups by hair glossiness still can, eyes have god, and are in high spirits, feces is rare partially, external irritant is defence hides attitude.Each organizes rat experiment front and back body weight no significant difference.
6.2 vagina epithelium exfoliative cyte cardiac index,contrast index,cornification index (table 6-1)
Table 6-1 respectively organizes rat experiment front and back keratinocyte index
| Group | ??N | CI (%) before the experiment | Experiment back CI (%) |
| Blank group | ??10 | ??43.18±8.15 | ??45.90±6.32** |
| Model group | ??10 | ??42.98±5.63 | ??79.59±4.23 |
| The spironolactone group | ??10 | ??42.63±9.01 | 66.89 native 6.51* |
| Breast disease spirit group | ??10 | ??43.21±7.46 | ??50.68±4.92** |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result shows: model group experiment back Cl is higher than the preceding Cl of experiment, and utmost point significant difference (P＜0.01) is arranged; Experiment back model group Cl is higher than newborn disease spirit group Cl, and utmost point significant difference (P＜0.01) is arranged.
6.3 influence to the rat blood serum gonadal hormone
6.3.1 to rat blood serum estradiol (E
2) influence (table 6-2)
Table 6-2 respectively organizes rat blood serum E
2Comparison
| Group | ??N | Serum E 2(pg/ml) |
| Blank group | ??10 | ??25.52±9.89** |
| Model group | ??10 | ??365.35±78.03 |
| The spironolactone group | ??10 | ??273.15±72.36* |
| Breast disease spirit group | ??10 | ??123.27±36.56** |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: blank group is lower than each group, and utmost point significant difference (P＜0.01) is arranged; Model group is higher than blank group, newborn disease spirit group has utmost point significant difference (P＜0.01); Model group is higher than positive controls, and there were significant differences (P＜0.05).
6.3.2 influence (table 6-3) to rat blood serum progesterone (P)
Table 6-3 respectively organizes the influence of rat blood serum P
| Group | ??N | Blood-serum P (pg/ml) |
| Blank group | ??10 | ??16.97±13.26** |
| Model group | ??10 | ??865.01±26.36 |
| The spironolactone group | ??10 | ??798.32±56.39* |
| Breast disease spirit group | ??10 | ??602.92±12.96** |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: blank group is lower than each group, and utmost point significant difference (P＜0.01) is arranged; Model group is higher than blank group, newborn disease spirit group, and utmost point significant difference (P＜0.01) is arranged; Model group is higher than positive controls, and there were significant differences (P＜0.05).
6.33 rat blood serum estradiol/progesterone influence (table 6-4)
Table 6-4 respectively organizes rat blood serum E
2The comparison of/P
| Group | ??N | Blood-serum P (pg/ml) |
| Blank group | ??10 | ??1.23±0.56** |
| Model group | ??10 | ??5.21±1.03 |
| The spironolactone group | ??10 | ??3.98±0.86* |
| Breast disease spirit group | ??10 | ??2.06±0.75** |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: blank group is lower than each group, and utmost point significant difference (P＜0.01) is arranged; Model group is higher than blank group, newborn disease spirit group, and utmost point significant difference (P＜0.01) is arranged; Model group is higher than positive controls, and there were significant differences (P＜0.05).
6.3.4 influence (table 6-5) to rat blood serum testosterone (T)
Table 6-5 respectively organizes the comparison of rat blood serum T
| Group | ??N | The content of rat blood serum T (ng/ml) |
| Blank group | ??10 | ??59.12±36.21** |
| Model group | ??10 | ??36.65±27.26 |
| The spironolactone group | ??10 | ??35.04±9.26 |
| Breast disease spirit group | ??10 | ??45.32±10.25* |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: model group is lower than blank group, and utmost point significant difference (P＜0.01) is arranged; Breast disease spirit group is higher than model group, and there were significant differences (P＜0.05); Breast disease spirit group is lower than blank group, and there were significant differences (P＜0.05).
6.3.5 influence (table 6-6) to rat blood serum prolactin antagonist (PRL)
Table 6-6 respectively organizes the comparison of rat blood serum PRL
| Group | ??N | The content of rat blood serum PRL (ng/ml) |
| Blank group | ??10 | ??3.76±0.76* |
| Model group | ??10 | ??5.36±2.56 |
| The spironolactone group | ??10 | ??4.42±0.78 |
| Breast disease spirit group | ??10 | ??3.69±0.56* |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: model group is higher than blank group, newborn disease spirit group, and there were significant differences (P＜0.05); Zero difference (P＞0.05) between all the other each groups.
6.4 influence (table 6-7) to the rat hypothalamus estrogen receptor
Table 6-7 respectively organizes the comparison of rat hypothalamus ER
| Group | ??N | The content of rat hypothalamus ER (ng/ml) |
| Blank group | ??10 | ??4291078.20±10235647.10** |
| Model group | ??10 | ???1456231.01±6958712.20 |
| The spironolactone group | ??10 | ???3856891.02±1236547.21** |
| Breast disease spirit group | ??10 | ??4045684.08±11235634.30** |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
IOD is an integral optical density, is meant the integrated value of measured matter sectional area internal optical density, the total content of expression extinction material.The IOD value is big more, illustrates that mensuration amount of substance or staining reaction color are dark more, and quantity is many more.
The result represents: model group is lower than all the other each groups, and there were significant differences (P＜0.01); Zero difference (P＞0.05) between all the other each groups.
6.5 the influence of rat hypothalamus beta-endorphin content (table 6-8)
Table 6-8 respectively organizes the comparison of rat hypothalamus beta-endorphin
| Group | ??N | The content of rat hypothalamus beta-endorphin (pg/ml) |
| Blank group | ??10 | ??69.56±34.25** |
| Model group | ??10 | ??821.562±623.45 |
| The spironolactone group | ??10 | ??545.23±89.63* |
| Breast disease spirit group | ??10 | ??123.23±28.56** |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: model group is higher than each group, and utmost point significant difference (P＜0.01) is arranged; The spironolactone group is higher than blank group, newborn disease spirit group, and utmost point significant difference (P＜0.01) is arranged.
6.6 influence to rat brain stem neurotransmitter
6.6.1 influence (table 6-9) to rat brain stem norepinephrine
Table 6-9 respectively organizes the comparison of rat brain stem NE
| Group | ??N | The content (ug/g) of rat brain stem NE |
| Blank group | ??10 | ??0.0712±0.0123* |
| Model group | ??10 | ??0.1025±0.02564 |
| The spironolactone group | ??10 | ??0.0980±0.0336* |
| Breast disease spirit group | ??10 | ??0.0705±0.0156* |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: model group is higher than each group, and there were significant differences (P＜0.05); Breast disease spirit group and blank group there was no significant difference.
6.6.2 influence (table 6-10) to rat brain stem dopamine
Table 6-10 respectively organizes the comparison of rat brain stem DA
| Group | ??N | The content (ug/g) of rat brain stem DA |
| Blank group | ??10 | ??0.8125±0.1203* |
| Model group | ??10 | ??0.6852±0.2036 |
| The spironolactone group | ??10 | ??0.7056±0.2541 |
| Breast disease spirit group | ??10 | ??0.7821±0.2956* |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: model group is lower than newborn disease spirit group, blank group, and there were significant differences (P＜0.05), and model group and spironolactone group do not have significant difference.
6.6.3 influence (table 6-11) to rat brain stem 5-hydroxy tryptamine
Table 6-11 respectively organizes the comparison of rat brain stem 5-HT
| Group | ??N | The content (ug/g) of rat brain stem 5-HT |
| Blank group | ??10 | ??0.1498±0.0365* |
| Model group | ??10 | ??0.1203±0.0265 |
| The spironolactone group | ??10 | ??0.1346±0.0365 |
| Breast disease spirit group | ??10 | ??0.1512±0.0236* |
Annotate: compare * with model group: P＜0.05 * *: P＜0.01
The result represents: model group is lower than newborn disease spirit group, blank group, and there were significant differences (P＜0.05), and model group and spironolactone group do not have significant difference.
Experimental result
To sum up, exogenous estrogen can cause and continue the high estrogen level in the experimental rat body, and shows necessarily between high estrogen and serum prolactin antagonist, neurotransmitter, hypothalamus estrogen receptor, the tissue hyper-microstructure and get in touch.
Experiment shows that simultaneously compare with the blank group, the persistence high estrogen can make serum estradiol, estradiol/progesterone ratio, serum prolactin antagonist, hypothalamus beta-endorphin content increase; Make hypothalamus estrogen receptor decreased number; Neurotransmitter is changed, and wherein 5-hydroxy tryptamine, dopamine are on a declining curve, and norepinephrine is in rising trend.
Medicine of the present invention can reduce estradiol too high in the serum, increases serum progesterone content, and estradiol/progesterone, prolactin antagonist, hypothalamus beta-endorphin are reduced to and blank group zero difference; The hypothalamus estrogen receptor raises and blank group zero difference; Increase brain stem 5-hydroxy tryptamine, DOPAMINE CONTENT IN RABBIT, reduce the noradrenaline cellulose content, make it to return to and blank group zero difference.Though spironolactone also can make too high estrogen, prolactin antagonist, hypothalamus beta-endorphin descend; Serum progesterone, hypothalamus estrogen receptor are risen; But compare with newborn disease spirit group, neurotransmitter serotonin, dopamine reduce more.This shows that medicine of the present invention has better balance adjustment effect.
Test two newborn disease spirit granule therapy premenstrual tension syndrome reversed syndrome of mepatic qi 60 examples
1.1PMS diagnostic criteria is with reference to Ministry of Health of the People's Republic of China. clinical research guideline [S] .1997.1-2. of new Chinese medicine treatment premenstrual tension syndrome formulates.
1.2 the syndrome diagnostic criteria is with reference to People's Republic of China's Chinese medicine industry standard traditional Chinese medical science disease diagnosis criterion of therapeutical effect [S]. Nanjing: publishing house of Nanjing University, 1994.63-65 formulates.
1.3 state of an illness grade scale is formulated with reference to " new Chinese medicine treatment premenstrual tension syndrome clinical research guideline ".1. slight: little have a headache, dizziness, and breast expands, or feels pain slightly, and is in a disturbed state of mind, and face is impractical, and work and study are as usual.2. moderate: dizziness headache, breast expands, vexed insomnia, psychentonia or melancholy, limb edema still can work and study.3. severe: severe headache is unbearably, and is dizzy, blurring of vision, and the cardiopalmus sleeplessness, distending pain of the breast can not touch clothing, face extremity or whole body swelling, finger submerged while pressing, or weight increase 1～2kg can not be adhered to working and learning.
Meet above-mentioned disease diagnostic criteria 1.4 include in exclusion standard, the age is at 18～40 years old, do not have obviously to merge with double and holds the disease person under the arm and include the observation case in.Meet the standard of including in but belong to gestation or women breast-feeding their children, be associated with serious primary disease such as cardiovascular, kidney and hemopoietic system, the psychotic gets rid of.
2 test methods
2.1 grouping is observed patient's 60 examples altogether with this test of Therapeutic Method, adopt to be divided into two groups at random, matched group and treatment group, grouping case age, the course of disease, the state of an illness, symptom, basal body temperature, hormonal readiness are learned processing by statistics, difference that there are no significant, the tool comparability.All case is all from beginning to take through preceding 10 days, and 10 days is 1 course of treatment, takes 2 menstrual cycle continuously.To treating back clinical recovery, produce effects and effective patient, follow up a case by regular visits to 3 menstrual cycle, observe and whether recur.
2.2 medicine treatment group: newborn disease spirit granule (made), 84g every day (in the crude drug amount), po, tid, warm water delivery service according to embodiment 2.Breast disease spirit granule effluent northern part of the country gold Pharmaceutical Co., Ltd provides lot number: 060702.Matched group: ease pill, each 9g, po, bid, warm water delivery service.Ease pill is produced lot number: 060602 by Linyi, Shandong silver passeris montani saturati Rhizoma Dioscoreae factory.
3 observation index
3.1 clinical symptoms, sign change before and after the curative effect observation treatment; Period in a medicine menstrual cycle and menstrual blood volume, color, qualitative changeization; Examination of basal body temperature; Endocrine is measured; The body weight weighing.
3.2 safety observation blood, urine, just conventional: treat the forward and backward routine test inspection of carrying out; The heart, liver, kidney function test: treat forward and backward carry out electrocardiogram, liver function (ALT), renal function (Bun, Cr) inspection.
4 curative effect determinate standards
Clinical recovery: clinical symptom disappearance, examination of basal body temperature or endocrine are measured normal substantially, and treatment finishes back 3 menstrual cycle of observation does not have recurrence, and the tcm symptom integration reduces more than 90%.Produce effects: cardinal symptom is clearly better, and basal body temperature or endocrine are measured near normal, and treatment end back is observed 3 menstrual cycle and do not increased the weight of.The tcm symptom integration reduces more than 60%, less than 90%.Effectively: the controlled degree of cardinal symptom alleviates to some extent, though treatment finishes the rear section symptom repeatedly, alleviates to some extent before the treatment.The tcm symptom integration reduces more than 30%, less than 59%.Invalid: various clinical symptoms do not have improvement or increase the weight of.The tcm symptom integration reduces less than 30%.
5 statistical procedures
The grade classified data is relatively used Ridit and is analyzed; Enumeration data is used X
2Check; Measurement data is used the t check.
Experimental result:
1, clinical efficacy
Each is organized patient's clinical efficacy and sees Table 1, treat 2 menstrual cycle after, treatment group and matched group clinical efficacy are relatively analyzed P＜0.01 through Ridit, and significant differences is arranged, the clinical efficacy of treatment group significantly is better than matched group (seeing table 12 for details).
Table 12 liang group patient clinical observation on the therapeutic effect
2 follow up a case by regular visits to curative effect
Follow up a case by regular visits to 3 menstrual cycle, treatment group and matched group are followed up a case by regular visits to curative effect relatively, analyze through Ridit, and P＜0.01 has the curative effect of following up a case by regular visits to of significant differences explanation treatment group obviously to be better than matched group, sees Table 13.
Table 13 a liang group patient follows up a case by regular visits to observation of curative effect
Emulsion spirit granule soothing liver-QI for relieving depression can be used for the treatment of premenstrual syndrome.
The specific embodiment
Embodiment 1
Get Radix Bupleuri 60g, Rhizoma Cyperi 60g, Pericarpium Citri Reticulatae Viride 60g, Radix Paeoniae Rubra 60g, Radix Salviae Miltiorrhizae 80g, Semen Vaccariae 80g, Caulis Spatholobi 80g, Concha Ostreae 320g, Sargassum 80g, Thallus Laminariae (Thallus Eckloniae) 80g, Herba Epimedii 80g, Semen Cuscutae 80g.
Said medicine is added water, soaked 4 hours, decoct with water twice.2 hours for the first time, 1.5 hours for the second time, merge decoction liquor, filter, be concentrated into every 100ml decocting liquid phase when the 75g crude drug.
Embodiment 2
Get Radix Bupleuri 48g, Rhizoma Cyperi 48g, Pericarpium Citri Reticulatae Viride 48g, Radix Paeoniae Rubra 48g, Radix Salviae Miltiorrhizae 64g, Semen Vaccariae 64g, Caulis Spatholobi 79g, Concha Ostreae 160g, Sargassum 79g, Thallus Laminariae (Thallus Eckloniae) 79g, Herba Epimedii 79g, Semen Cuscutae 79g.
(1) Radix Bupleuri, Rhizoma Cyperi (processed with vinegar), Pericarpium Citri Reticulatae Viride, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Caulis Spatholobi, Concha Ostreae, Sargassum, Thallus Laminariae (Thallus Eckloniae), Herba Epimedii, Semen Cuscutae are decocted with water twice.2 hours for the first time, 1.5 hours for the second time, merge decoction liquor, filter filtrate for later use;
Rhizoma Cyperi (processed with vinegar) wherein is to adopt clean Rhizoma Cyperi, mixes (100 jin of every Rhizoma Cyperis are with 20 jin of vinegar) thoroughly with vinegar, vexed 12 hours, and to put in the pot and fry to little yellow, taking-up is dried.
(2) Semen Vaccariae is fried to pop to great majority with slow fire spend in vain.After cooling, add water, decoct twice, 1.5 hours for the first time, 1 hour for the second time, merge decoction liquor, filter, filtrate is concentrated into density and is about 1.1 (70～80 ℃), room temperature to be chilled to, the ethanol that adds equivalent makes precipitation, filters, and is standby behind the filtrate recycling ethanol;
(3) filtrate in (1) (2) is merged, be concentrated in right amount, add suitable amount of sucrose and dextrin, make the dissolved granule that every gram granule is equivalent to 5 gram crude drugs.
Embodiment 3
Get Radix Bupleuri 30g, Rhizoma Cyperi 30g, Pericarpium Citri Reticulatae Viride 30g, Radix Paeoniae Rubra 30g, Radix Salviae Miltiorrhizae 50g, Semen Vaccariae 50g, Caulis Spatholobi 50g, Concha Ostreae 160g, Sargassum 50g, Thallus Laminariae (Thallus Eckloniae) 50g, Herba Epimedii 50g, Semen Cuscutae 50g.
Prepare extract according to embodiment 2 described methods.Extract is made with extra care, is removed the thermal source processing and add distilled water according to the conventional method of Chinese medicine, regulates isoosmotic pressure with sodium chloride, filters fill.Make the injection that every 2ml is equivalent to crude drug 10g.
Embodiment 4-8 (seeing Table 14)
Table 14
Above embodiment all has 1, the 2 essentially identical experiment effects with embodiment, does not repeat them here.
Claims (2)
1. pharmaceutical composition that is used for the treatment of premenstrual syndrome is characterized in that it comprises the crude drug of following weight part ratio:
Radix Bupleuri 30-60 part, Rhizoma Cyperi 30-60 part, Pericarpium Citri Reticulatae Viride 30-60 part, Radix Paeoniae Rubra 30-60 part, Radix Salviae Miltiorrhizae 50-80 part, Semen Vaccariae 50-80 part, Caulis Spatholobi 50-80 part, Concha Ostreae 160-320 part, Sargassum 50-80 part, Thallus Laminariae (Thallus Eckloniae) 50-80 part, Herba Epimedii 50-80 part, Semen Cuscutae 50-80 part.
2. the pharmaceutical composition that is used for the treatment of premenstrual syndrome according to claim 1 is characterized in that the weight part ratio of said crude drug is:
Radix Bupleuri 48-56 part, Rhizoma Cyperi 48-56 part, Pericarpium Citri Reticulatae Viride 48-56 part, Radix Paeoniae Rubra 48-56 part, Radix Salviae Miltiorrhizae 64-74 part, Semen Vaccariae 64-74 part, Caulis Spatholobi 79-80 part, Concha Ostreae 160-180 part, Sargassum 79-80 part, Thallus Laminariae (Thallus Eckloniae) 79-80 part, Herba Epimedii 79-80 part, Semen Cuscutae 79-80 part.
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| Application Number | Priority Date | Filing Date | Title |
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| CN200810080254A CN101766743A (en) | 2008-12-29 | 2008-12-29 | Drug combination for treating permenstrual syndrome |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103638508A (en) * | 2013-12-03 | 2014-03-19 | 徐承香 | Traditional Chinese medicine for treating premenstral syndrome |
| CN106109814A (en) * | 2016-08-29 | 2016-11-16 | 河北国金药业有限责任公司 | The preparation method of breast disease spirit granule |
| CN106214904A (en) * | 2016-08-29 | 2016-12-14 | 河北国金药业有限责任公司 | Pharmaceutical composition treats the application in the female endocrine dyscrasia medicine that depression of liver-QI causes as preparation |
-
2008
- 2008-12-29 CN CN200810080254A patent/CN101766743A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103638508A (en) * | 2013-12-03 | 2014-03-19 | 徐承香 | Traditional Chinese medicine for treating premenstral syndrome |
| CN103638508B (en) * | 2013-12-03 | 2016-08-17 | 徐承香 | The Chinese medicine for the treatment of premenstrualtension syndrome |
| CN106109814A (en) * | 2016-08-29 | 2016-11-16 | 河北国金药业有限责任公司 | The preparation method of breast disease spirit granule |
| CN106214904A (en) * | 2016-08-29 | 2016-12-14 | 河北国金药业有限责任公司 | Pharmaceutical composition treats the application in the female endocrine dyscrasia medicine that depression of liver-QI causes as preparation |
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