CN1241618C - Application of Ypsilandra herbs for preparing medicines for treating hemorrhagic diseases - Google Patents
Application of Ypsilandra herbs for preparing medicines for treating hemorrhagic diseases Download PDFInfo
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Abstract
The present invention discloses a new medicinal application of plants, more specifically an application of ypsilandra which belongs to plants to the prepration of medicine for treating hemorrhagic diseases. The ypsilandra belongs to plants and is one or some of ypsilandra thibetica, ypsilandra yunnanensis var, micranthahand-mazz, ypsilandra alpina Wang et. Tang, ypsilandra cavaleviei levl et vant and ypsilandra kansuensis. As the ypsilandra belongs to a plant crude medicine in whole, the ypsilandra has obvious blood stopping activity and uterus contracting action, can be made into various dosage forms and is suitable for treating various gynecological hemorrhagic diseases, particularly profuse menstruation, postpartum hemorrhages, functional uterine bleeding, hemorrhages after medicine abortion, uterine bleeding due to an intrauterine device, etc. The ypsilandra has the advantages and the characteristics of conspicuous curative effect, low price, safe and convenient operation, etc.
Description
Technical field
The present invention relates to the new pharmaceutical usage of plant, specifically, the present invention relates to new purposes with the pharmacy of Liliaceae Ypsilandra (Ypsilandra) platymiscium.
Background technology
Liliaceae Ypsilandra (Ypsilandra) platymiscium mainly is distributed with five kinds in China: Ypsilandra (Ypsilandra thibetica); The Yunnan Ypsilandra (Y.yunnanensis var, micranthaHand-Mazz); High mountain Ypsilandra (Y.alpina Wang et.Tang); Little Ypsilandra (Y.cavaleviei Levl et Vant), Gansu Ypsilandra (Y.kansuensis).According to " China's book on Chinese herbal medicine " (Shanghai science tech publishing house, JIUYUE was the 1st edition in 1999, the 8th volume, 149-150) record: the herb of liliaceous plant Ypsilandra (Ypsilandra thibetica), the right Paeonia ostii of high eyebrow by name has another name called YIZHIHUA (" Guangxi higher plant register "), the stone Paeonia ostii, red with oneself, little savoy (" Chinese Higher plant illustrated handbook "); Purposes among the people is heat clearing away, detoxifcation, eliminating stagnation, and diuresis cures mainly scrofula, dysuria, edema.
Modern study report to chemistry, pharmacologically active and the clinical practice of Ypsilandra (Ypsilandra.) platymiscium is very few at present, only having Chinese patent CN 10810363C to disclose with a kind of Ypsilandra (Ypsilandra thibetica) plant herb is raw material, separate the furan steroid class steroidal saponin body tool active anticancer that is obtained with chemical method, this patent of invention is also recorded in U.S. chemical abstract (Kawabc N, et al.CS, 1996,124:325368Y).Up to now, the still last research report of seeing any Ypsilandra platymiscium styptic activity.
About hemorrhage, mainly comprise respiratory tract hemorrhage (hemoptysis, spitting of blood), digestive tract hemorrhage (spit blood, have blood in stool), urinary tract hemorrhage (hematuria), department of obstetrics and gynecology hemorrhage etc. are multiple, and at various hemorrhages, the application of haemostatic medicament is the key link of such disease treatment.In the general so-called department of obstetrics and gynecology hemorrhage, menorrhagia, postpartum hemorrhage, dysfunctional uterine hemorrhage, artificial abortion or hemorrhage after drug abortion, intrauterine contraceptive device in utero cause that sub-official is hemorrhage clinically comparatively to be seen more.Dysfunctional uterine hemorrhage is a common gynecological disease, and modern medicine is treated this sick principle and is hemostasis, adjustment cycle, promotion ovulation, and the main medicine of hemostasis and adjustment cycle is a gonadal hormone, but gonadal hormone has certain side effect, and using method is loaded down with trivial details, and its application has certain limitation.Drug induced abortion (being called for short medicine stream) is the method for a kind of safety, effectiveness termination of pregnancy; But hemorrhage behind the medicine stream is clinical problem of failing fine solution always.The intrauterine device contraception has advantages such as safe, effective and easy, is one of fertility control method of extensive use, but hemorrhage being still perplexed the subject matter of being with the device person after putting device, and the clinical indomethacin that uses is aided with vitamin E, but effect is undesirable.Therefore, research and develop new haemostatic medicament, the haemostatic medicament in particular for treatment department of obstetrics and gynecology hemorrhage will have good potential applicability in clinical practice.
Summary of the invention
The inventor finds that through long-term screening study the Ypsilandra platymiscium has stronger styptic activity, can be used for the treatment of multiple hemorrhage.The purpose of this invention is to provide the purposes that the Ypsilandra platymiscium is used for preparing the medicine for the treatment of hemorrhage, in particular for the purposes in the preparation treatment department of obstetrics and gynecology hemorrhage.
Technical scheme: the invention provides the new purposes of Ypsilandra (Ypsilandra) platymiscium in the medicine of preparation treatment hemorrhage.Described Ypsilandra (Ypsilandra) platymiscium is Ypsilandra (Ypsilandra thibetica); Yunnan Ypsilandra (Y.yunnanensis var, micrantha Hand-Mazz); High mountain Ypsilandra (Y.alpina Wang et.Tang); Little Ypsilandra (Y.cavaleviei Levl et Vant), in the Gansu Ypsilandra (Y.kansuensis) any one or a few.Further, be to be that active component prepares described medicine with the water of Ypsilandra platymiscium crude drug in whole or Ypsilandra platymiscium or the extract of organic solvent.
The present invention also provides a kind of Ypsilandra (Ypsilandra) genus plants extract that is used to prepare the medicine for the treatment of hemorrhage.Described Ypsilandra (Ypsilandra) genus plants extract is by Ypsilandra (Ypsilandra thibetica); Yunnan Ypsilandra (Y.yunnanensisvar, micrantha Hand-Mazz); High mountain Ypsilandra (Y.alpina Wang et.Tang); Little Ypsilandra (Y.cavaleviei Levl et Vant), any one or a few preparation in the Gansu Ypsilandra (Y.kansuensis).Specifically, described extract is from stem, leaf or the root of described plant.Further, described extract is by water or organic solvent extraction.
Above-mentioned Ypsilandra (Ypsilandra) genus plants extract has following HPLC finger printing feature, promptly has five obvious characteristic peaks simultaneously, is respectively: Y
1(retention time is 11.240 ± 0.2min), Y at the peak
2(retention time is 17.1 ± 0.3min), Y at the peak
3(retention time is 18.7 ± 0.2min), Y at the peak
4(retention time is 19.5 ± 0.2min), Y at the peak
5(retention time is 25.0 ± 0.2min) at the peak.
Further, described Ypsilandra (Ypsilandra) genus plants extract contains saponin, specifically, contains pennogenin (Pennogenin saponins) compounds, more particularly contains pennogenin (Pennogenin saponins) monomer.
The present invention also provides a kind of pharmaceutical composition, contains above-mentioned Ypsilandra (Ypsilandra) genus plants extract, adds pharmaceutically acceptable carrier or complementary composition mixes.
Above-mentioned Ypsilandra (Ypsilandra) genus plants extract can be used for preparing the particularly medicine of department of obstetrics and gynecology hemorrhage of hemorrhage.
The present invention also provides a kind of pharmaceutical composition, is to be mixed by Ypsilandra platymiscium crude drug in whole and pharmaceutically acceptable carrier or complementary composition.
The dosage form of described pharmaceutical composition is an oral formulations.
The invention provides the new purposes of Ypsilandra (Ypsilandra) platymiscium in the medicine of preparation treatment hemorrhage, described hemorrhagic disease is the department of obstetrics and gynecology hemorrhages, concrete is meant, menorrhagia, postpartum hemorrhage, dysfunctional uterine hemorrhage, artificial abortion or medicine stream postoperative hemorrhage, or intrauterine device causes metrorrhagia.
When the Ypsilandra platymiscium is used to prepare the medicine for the treatment of hemorrhage, can be that Ypsilandra platymiscium crude drug in whole directly is processed into medicine, also can be Ypsilandra platymiscium crude drug in whole to be carried out Chemical Decomposition extract, various extracts (comprise water extract, extractive with organic solvent, saponin extract, partially such saponin extract) are prepared into medicine.Also can be Ypsilandra platymiscium crude drug in whole or its various extracts to be cooperated with other plant amedica make compound preparation.Can be that herbal mixture and preparation thereof are formed in Ypsilandra platymiscium crude drug in whole and other hemostasis quasi-tradition drug matching.
Any is a raw material with Ypsilandra platymiscium crude drug in whole (herb aerial parts, rhizome), and directly processing and preparing becomes medicine.Can be above-mentioned crude drug in whole to be made the back only pulverize, cross the 80-120 mesh sieve, make fine powder, again that fine powder is encapsulated, or be prepared into capsule, tablet, pill, granule, powder.
Any is a raw material with Ypsilandra platymiscium crude drug in whole (herb), is prepared into medicine after tentatively extracting.Can adopt the various conventional extracting method in the modern technologies to extract, for example, be solvent extraction with water, and perhaps with organic solvent extraction such as ethanol, methanol, preferred alcohol extracts.The extract of gained, add pharmaceutically acceptable carrier, as starch, lactose, sucrose, maltose, dextrin, cellulose family, agar, magnesium stearate, Talcum, vegetable oil, arabic gum, gelatin etc. can be made multiple dosage forms such as capsule, tablet, pill, powder, granule, syrup, injection.
Any is a raw material with Ypsilandra platymiscium crude drug in whole, and extraction separation is prepared into medicine after going out saponin.Can adopt following conventional saponin separating and extracting process: the back pulverizing is coarse powder through clean system with crude drug, water, methanol or ethanol, room temperature or heating (comprising backflow) were extracted 1～3 hour, can repeat to extract 1～3 time, elimination medicinal residues then, filtrate is concentrated into certain density concentrated solution, stand for standby use under normal pressure or decompression.The said extracted concentrated solution is used macroporous resin adsorption behind precipitant, be the ethanol elution macroporous resin of 30-90% with concentration then, after the eluent reclaim under reduced pressure, gets extractum, becomes dry powder through vacuum or lyophilization.Also above-mentioned extractum can be the bisnosaponin monomer or mix glycosides through further separation and purification.
Any is a raw material with Ypsilandra platymiscium crude drug in whole, the herbal mixture of compatibility hemostatic function that other Chinese medicine is formed for.
The inventor is through the deeply chemical analysis research repeatedly to above-mentioned five kinds of Ypsilandra platymisciums and extract thereof, set up the HPLC finger printing (referring to accompanying drawing 1, Fig. 2) of Ypsilandra platymiscium or its extract, and the finger printing of finding Ypsilandra platymiscium or its various extracts has five obvious characteristic peaks simultaneously, is respectively: Y
1(retention time is 11.240 ± 0.2min), Y at the peak
2(retention time is 17.1 ± 0.3min), Y at the peak
3(retention time is 18.7 ± 0.2min), Y at the peak
4(retention time is 19.5 ± 0.2min), Y at the peak
5(retention time is 25.0 ± 0.2min) at the peak.Having above-mentioned five marked featurees that characteristic peak is Ypsilandra platymiscium or its various extracts in the HPLC finger printing simultaneously, is its important diagnostic characteristics that obviously is different from other plant.
Ypsilandra platymiscium crude drug in whole, or its water extract, or its extractive with organic solvent or its saponin extract or its saponin extract partially such, or the medicine of its Chinese medicine compound preparation and preparation thereof have significant hemostasis and shrink the uterus pharmacological action.
Beneficial effect: because Ypsilandra platymiscium crude drug in whole, or its water extract, or its extractive with organic solvent, or its saponin extract, or its pennogenin extract, or the medicine and the preparation thereof of its medicaments compound preparation, have significant styptic activity and shrink the uterus effect, can be made into capsule, tablet, granule, multiple dosage form such as oral liquid or injection, be applicable to hemorrhage, especially menorrhagia, postpartum hemorrhage, the function metrorrhagia, medicine stream postoperative hemorrhage, intrauterine device causes the treatment of multiple gynecological bleeding such as metrorrhagia, have evident in efficacy, cheap, advantageous feature such as safe and convenient to use also provides a kind of new medicine source plant resource for the preparation hemorrhage especially medicine of gynecology hemorrhagic disease.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Description of drawings:
Fig. 1 is the HPLC finger printing of the former plant of Ypsilandra (Ypsilandra thibetica)
Fig. 2 is the HPLC finger printing of the former plant of Yunnan Ypsilandra (Y.yunnanensis var, micrantha Hand-Mazz)
Fig. 3 is the HPLC finger printing of the former plant of Rhizoma Paridis (Paris polyhylla Smith var.yunnanensis (Franch.) Hand.-Mazz)
Fig. 4 is that Rhizoma Paridis mixes the HPLC finger printing with Ypsilandra two kind of plant
The specific embodiment
Embodiment 1: the preparation of Ypsilandra, Yunnan Ypsilandra, high mountain Ypsilandra crude drug in whole medicine
With a kind of in the Ypsilandra platymiscium be raw material, it is Ypsilandra (Ypsilandra thibetica) plant herb, or Yunnan Ypsilandra (Y.yunnanensis var, micrantha Hand-Mazz), or high mountain Ypsilandra (Y.alpina Wang et.Tang), pulverize according to a conventional method after the clean system, sieve, make granularity less than 60 purpose Ypsilandra fine powder 8.5g, fine powder incapsulates, sterilization, packing.
Embodiment 2: the preparation of Ypsilandra, Yunnan Ypsilandra, high mountain Ypsilandra water extract
With a kind of in the Ypsilandra platymiscium be raw material, be Ypsilandra (Ypsilandra thibetica) plant herb, or Yunnan Ypsilandra (Y.yunnanensis var, micrantha Hand-Mazz) herb, or high mountain Ypsilandra (Y.alpina Wang et.Tang) herb, remove plant rotted leaf and impurity, get crude drug in whole 500g, pulverize the back and add 10 times of water gagings, heating and refluxing extraction 2 hours, filtering residue adds 10 times of water gagings again, and heating and refluxing extraction 2 hours is filtered.Merge filtrate twice, concentrate the Ypsilandra water extract, or Yunnan Ypsilandra water extract, or high mountain Ypsilandra water extract.
Embodiment 3: the preparation of Ypsilandra ethanol extraction, Yunnan Ypsilandra ethanol extraction, high mountain Ypsilandra ethanol extraction
Ypsilandra (Ypsilandra thibetica) is removed plant rotted leaf and impurity, gets crude drug in whole 1000g, adds 70% alcoholic solution 8L after the pulverizing, heating and refluxing extraction 2 hours, and filtering residue adds 6 liters of 70% alcoholic solution again, and heating and refluxing extraction 2 hours is filtered.Merge filtrate twice, concentrate ethanol extraction (to call CHY-1 in the following text).
Yunnan Ypsilandra (Y.yunnanensis var, micrantha Hand-Mazz) is removed plant rotted leaf and impurity, gets crude drug in whole 1000g, add 70% alcoholic solution 8L after the pulverizing, heating and refluxing extraction 2 hours, filtering residue adds 6 liters of 70% alcoholic solution again, heating and refluxing extraction 2 hours is filtered.Merge filtrate twice, concentrate ethanol extraction (to call CHY-2 in the following text).
High mountain Ypsilandra (Y.alpina Wang et.Tang) is removed plant rotted leaf and impurity, gets crude drug in whole 1000g, adds 70% alcoholic solution 8L after the pulverizing, heating and refluxing extraction 2 hours, and filtering residue adds 6 liters of 70% alcoholic solution again, and heating and refluxing extraction 2 hours is filtered.Merge filtrate twice, concentrate ethanol extraction (to call CHY-3 in the following text).
Embodiment 4: the preparation of Ypsilandra saponin extract and preparation thereof
Ypsilandra (Ypsilandra thibetica) is removed impurity, gets crude drug in whole 1000g, adds 70% alcoholic solution 8L after the pulverizing, heating and refluxing extraction 1.5 hours, and filtering residue adds 6L 70% alcoholic solution again, and heating and refluxing extraction 1 hour is filtered.Merge filtrate twice, be concentrated into finite concentration, stand for standby use.Or, with containing 50% Diluted Alcohol liquid eluting pillar, collect eluent then with the water liquid reuse macroporous resin adsorption of its concentrated solution after precipitant is handled, after the eluent reclaim under reduced pressure, extractum, vacuum drying or be spray dried to dry powder obtains about 70g extract dry powder (to call CHY-4 in the following text).Through foam stability test, the positive reaction of acetic anhydride-strong sulfuric acid response, the TLC qualitative identification is the steroidal saponin constituents.The further separation and purification of dry powder can be got pennogenin constituents or saponin monomer partially such.Separating obtained pennogenin monomer, through chemical analysis, its chemical constitution, spectroscopic data are as follows: molecular formula is: C
51H
82O
21FAB
+-MS:M
+=1030, m/z:884 (1030-rha) C
45H
72O
17 +, 738 (884-146) C
39H
62O
13 +, IRv
Max KBrCm
-1: 3408,2939,1625,1456,1378,1242,1129,1052,979,916,836.The chemical potential of C13NMR and HINMR indication aglycon (C1-C27) is transplanted δ C (H) and is respectively: 37.21 (1.73), 30.21 (2.07), 77.77 (3.83), 39.01 (2.75), 140.83,121.39 (5.29), 32.49 (1.53) .32.40.50.30 (0.94) .37.61,21.0 (1.50), 32.13 (1.54), 45.19.53.09 (2.04, m), 32.13 (1.66), 90.20 (4.48) .90.08.17.20 (0.95, s), 19.50 (1.07, s), 44.82 (2.25), 9.81 (1.22, d, J=7.1), 109.88,31.87 (1.85) .28.86 (1.55), 30.48 (2.05), 66.76 (3.50), 17.37 (0.67, d, J=5.4).The chemical potential of glycosyl part is transplanted δ C (H) and is respectively: 100.37 (4.92, d, J=7.8), 78.09 (4.25), 77.03 (3.58), 77.77 (4.40), 78.01 (4.18), (61.25 4.02,4.15), 102.22 (6.39) .72.90 (4.50), 72.55 (4.84), 74.18 (4.32), 69.60 (4.93), 18.70 (1.58, d, J=5.8), 102.26 (5.85), 73.33 (4.63), 70.45 (4.34), 80.45 (4.41), 18.48 (1.75, d, J=6.1), 103.34 (6.28), 72.90 (4.48), 72.68 (4.89), 74.05 (4.56), 70.46 (4.92), 18.93 (1.57, d, J=5.8)
The making of tablet: comprise ordinary tablet, diaphragm, enteric coatel tablets etc.With above-mentioned saponin extract dry powder, add an amount of diluent such as starch, dextrin, mannitol, microcrystalline cellulose etc., an amount of binding agent such as water, ethanol, starch slurry, gelatin, cellulose etc., an amount of disintegrating agent such as dried starch, Sodium Hydroxymethyl Stalcs, the end, replace hydroxypropyl cellulose, sodium alginate etc., and proper amount of lubricating agent such as magnesium stearate, Pulvis Talci, Polyethylene Glycol etc., can add an amount of sweeting agent, as D-xylose, xylitol, maltose alcohol, sweet taste centautin, aspartame etc.Wet granulation routinely, tabletting behind dry back granulate or the dry granulation as the bag Film coated tablets, may be configured as membrane material such as cellulose family, polyethylene glycols etc., and coating routinely divides during pack into airtight bottle or silver hopes extremely.
Embodiment 5: Ypsilandra, Yunnan Ypsilandra, high mountain Ypsilandra ethanol extraction and Ypsilandra saponin extract go out the influence of clotting time to mice
(1) Ypsilandra, Yunnan Ypsilandra, high mountain Ypsilandra ethanol extraction and Ypsilandra saponin extract are to the influence of clotting time of mice: adopt clotting time of mice to measure capillary glass-tube method, can observe medicine mice is shortened clotting time.
60 of Kunming mouses, male and female half and half are divided into 6 groups: the blank group; CHY-1 organizes (being embodiment 3 gained Ypsilandra ethanol extractions, as follows); CHY-2 organizes (being embodiment 3 gained Yunnan Ypsilandra ethanol extractions, as follows); CHY-3 organizes (being embodiment 3 gained high mountain Ypsilandra ethanol extractions, as follows); CHY-4 high and low dose group (being embodiment 4 gained Ypsilandra saponin extracts, as follows).All irritate stomach, give normal saline and Ypsilandra extract respectively for every group by 0.2ml/10g dosage.Insert the mice ophthalmic with capillary glass tube after 1 hour and adjoin the ball rear vein beard, about deeply 4-5mm, the slight light withdrawal again of rotating.Pick up counting in the autoblood inflow pipe, blood is filled with back taking-up capillary tube and is put on the table, every 30 seconds about instrument 0.5cm of folding section two ends capillary tube, and slowly draw back to the left and right, whether the observation place of fractureing has the blood clotting silk, till the appearance of blood clotting silk, between lasting, institute is the blood clotting time, and the meansigma methods of capillary tube two end datas is the blood clotting time of this Mus.The results are shown in Table 1
Table 1: three kinds of Ypsilandra ethanol extractions and Ypsilandra saponin extract are to the influence (X scholar SD) of clotting time of mice
| Group | Animal groups | Dosage g/Kg | Clotting time (sec) |
| Blank group CHY-1 CHY-2 CHY-3 CHY-4 CHY-4 | 10 10 10 10 10 10 | --- 0.40 0.40 0.40 0.02 0.01 | 58±27 40±16 * 41±8 * 39±15 * 37±9 * 45±16 * |
* compare p＜0.05 with the blank group
Table 1 result shows that Ypsilandra ethanol extraction, Yunnan Ypsilandra ethanol extraction, high mountain Ypsilandra ethanol extraction, Ypsilandra saponin extract all have the effect of obvious shortening clotting time of mice.
(2) Ypsilandra, Yunnan Ypsilandra, high mountain Ypsilandra ethanol extraction and Ypsilandra saponin extract are cut the influence of tail bleeding stopping period to mice
60 of Kunming mouses, male and female half and half are divided into 6 groups: the blank group; CHY-1 organizes (being embodiment 3 gained Ypsilandra ethanol extractions, as follows); CHY-2 organizes (being embodiment 3 gained Yunnan Ypsilandra ethanol extractions, as follows); CHY-3 organizes (being embodiment 3 gained high mountain Ypsilandra ethanol extractions, as follows); CHY-4 high and low dose group (being embodiment 4 gained Ypsilandra saponin extracts, as follows).Method: after the mice administration, it is hemorrhage mensuration to measure the tail point.Cut off Mus tail point 1cm, inhale every 30sec with filter paper and remove effusive voluntarily blood, stop to bleeding, the filter paper of cutting band blood washes bloodstain with washing liquid, and by 7320 type spectrophotometric instrumentation light transmittances (T value), T value is big more, and amount of bleeding is more little.The results are shown in Table 2.
Table 2: three kinds of Ypsilandra ethanol extractions and Ypsilandra saponin extract
Influence to mice bleeding time and amount of bleeding
| Group | Animal groups | Dosage g/Kg | Bleeding time (sec) | Light transmittance (T) |
| Blank group CHY-1 CHY-2 CHY-3 CHY-4 CHY-4 | 10 10 10 10 10 10 | --- 0.40 0.40 0.40 0.02 0.01 | 276±127 150±96 * 145±86 * 151±80 * 130±92 ** 163±90 * | 26±26 60±32 * 61±30 * 58±28 * 55±33 * 54±33 * |
*Compare p＜0.01 with plain paper,
*With the blank group than school p＜0.05
Table 2 result shows, Ypsilandra platymiscium crude drug in whole and multiple extract thereof: Ypsilandra ethanol extraction, Yunnan Ypsilandra ethanol extraction, high mountain Ypsilandra ethanol extraction, Ypsilandra saponin extract all have obvious minimizing mice to cut bleeding time and amount of bleeding effect behind the tail.
Embodiment 6: the Ypsilandra saponin extract is to the effect of isolated rat uterine smooth muscle: adopt isolated rat uterine smooth muscle test method, observe the influence of medicine to rat uterus smooth muscle contraction intensity and contraction frequency.
Get 220-240g, the female wistar healthy rat of unpregnancy takes out the uterus with fertility once,, high dose group (be embodiment 3 gained Ypsilandra saponin extracts) test low with CHY-4.In the experiment before continuous two days, intramuscular injection diethylstilbestrol 0.1mg/Kg/ time, the adjustment animality cycle.The cervical vertebra dislocation method is put to death rat, cuts open the belly and takes out the uterus, and the two ends of a side cornua uteri are pricked with toe-in respectively, and isolated uterine is put into the not open close oxygen of the Magnus' bath that fills the 10ml tyrode's solution, keeps 37 ± 0.5 ℃ of constant temperature nutrition.Fixedly lower end, upper end link to each other with the tenaculum of tension pick-up, waited for quietly 20-30 minute, and changed liquid 2-3 time, give uterus load 1g and maintenance, treat that the uterus is stable, after computer display wave mode do not occur, (adopt accumulative total dosing method, medicine was added by low concentration successively and causes high concentration in the beginning administration, the medicine final concentration is meant that medicine is dissolved in the concentration in the 10ml tyrode's solution in the nutritional solution), observe and trace curvilinear motion, calculate and shrink wave height and contraction frequency, the results are shown in Table 3:
Table 3: the Ypsilandra extract is to the contraction in isolated rat uterus
| Group | Dosage μ g/ml | n | Shrink wave height (cm) | Frequency (second/ripple) |
| CHY-4 CHY-4 CHY-4 before the administration | - 1.6 3.2 6.4 | 8 8 8 8 | 0 3.33±0.41 3.69±0.96 4.13±1.06 | 0 108.1±7.54 81.2±16.8 70.5±21.8 |
Table 3 result shows that Ypsilandra saponin extract 1.6 μ g/ml can cause uterine contraction, and increase with concentration, its wave height and the dependent enhancing of frequency show dose.
Experiment showed, that Ypsilandra platymiscium crude drug in whole and multiple extract thereof have stronger contraction uterine smooth muscle effect.
Embodiment 6: Ypsilandra saponin extract studies on acute toxicity
Get Ypsilandra extract C HY-4 by 500mg/kg (be equivalent to clinical application amount 1000 times) to 30 gastric infusions of Kunming kind female mice (body weight is 18-22g), continuous 7 days, observe chmice acute toxicity.The result: it is little that normal type changes difference, and none is only dead, puts to death after gross necropsy is not seen obvious pathology damage.
Embodiment 7: Ypsilandra and Yunnan Ypsilandra HPLC finger printing
Chromatographic condition: HP1100 high performance liquid chromatograph
Chromatographic column: RP-18; Flow velocity: 0.8ml/min; Column temperature: 30 ℃; Eluant: second is fine-water
The HPLC finger printing of Ypsilandra (Ypsilandra thibetica) plant is seen Fig. 1, and five obvious characteristic peaks are respectively as seen from Figure 1: Y
1Peak (retention time is 11.2min), Y
2Peak (retention time is 17.1min), Y
3Peak (retention time is 18.7min), Y
4Peak (retention time is 19.5min), Y
5Peak (retention time is 25.0min).
The HPLC finger printing of Yunnan Ypsilandra (Y.yunnanensis var, micrantha Hand-Mazz) plant is seen Fig. 2, and five obvious characteristic peaks are respectively as seen from Figure 2: Y
1Peak (retention time is 11.219min), Y
2Peak (retention time is 16.828min), Y
3Peak (retention time is 18.828min), Y
4Peak (retention time is 19.640min), Y
5Peak (retention time is 25.160min).
Embodiment 8: Rhizoma Paridis and the contrast of Ypsilandra HPLC finger printing
The applicant once studied the C27 steroidal saponin of Rhizoma Paridis (Paris polyhylla Smith var.yunnanensis (Franch.) Hand.-Mazz), analyze with reference to above Ypsilandra (Ypsilandra thibetica) plant HPLC chromatographic condition and sample treatment, its finger printing is seen Fig. 2, as seen from Figure 2, the HPLC finger printing of the former plant of Rhizoma Paridis has 4 characteristic peak: P
1(retention time is 8.1 ± 0.1min), P at the peak
2(retention time is 19.4 ± 0.1min), P at the peak
3(retention time is at the peak
24.9 ± 0.1min), P
4The peak (retention time is 26.1 ± 0.1min), contrast Ypsilandra platymiscium characteristic peak, and both are different.
Under the same conditions, Rhizoma Paridis and Ypsilandra mixing are carried out the HPLC fingerprint map analyzing, its finger printing is seen Fig. 3, discovery is that (Y4 of Ypsilandra and Y5 content are far above the P2 and the P3 of Rhizoma Paridis the total steroidal saponin of two plants except that having Y4, P2 and Y5, P3 C27, see Fig. 1,3,4).It is 11.3,17.1,18.7 Y1 that Ypsilandra also has retention time under the experiment condition, three C27 steroidal saponins of Y2 and Y3.Therefore, the C27 steroidal glycoside of demonstration Ypsilandra has uniqueness.
Claims (16)
1. the purposes of Ypsilandra platymiscium in the medicine of preparation treatment hemorrhage.
2. according to the purposes of claim 1, it is characterized in that: described Ypsilandra platymiscium be in Ypsilandra, Yunnan Ypsilandra, high mountain Ypsilandra, little Ypsilandra or the Gansu Ypsilandra any one or a few.
3. according to the purposes of claim 1 or 2, it is characterized in that: described medicine is that the extract with Ypsilandra platymiscium crude drug in whole or Ypsilandra platymiscium is that active component prepares described medicine.
4, according to the purposes of claim 3, it is characterized in that: described medicine is that the extract with the water of Ypsilandra platymiscium or organic solvent is that active component is prepared into medicine.
5, purposes according to claim 4 is characterized in that: described Ypsilandra genus plants extract is from stem, leaf or the root of described plant.
6, purposes according to claim 5 is characterized in that: described Ypsilandra genus plants extract is by water or organic solvent extraction.
7, a kind of Ypsilandra genus plants extract that is used to prepare the medicine for the treatment of hemorrhage, it is characterized in that: the Ypsilandra genus plants extract has following HPLC finger printing feature, promptly have five obvious characteristic peaks simultaneously, be respectively: retention time is the Y of 11.240 ± 0.2min
1Peak, retention time are the Y of 17.1 ± 0.3min
2Peak, retention time are the Y of 18.7 ± 0.2min
3Peak, retention time are the Y of 19.5 ± 0.2min
4Peak, retention time are the Y of 25.0 ± 0.2min
5The peak.
8, a kind of Ypsilandra genus plants extract that is used to prepare the medicine for the treatment of hemorrhage, it is characterized in that: described extract contains bisnosaponin compound.
9, Ypsilandra genus plants extract according to claim 8, it is characterized in that: described extract contains the pennogenin monomer.
10, a kind of pharmaceutical composition for the treatment of hemorrhage is characterized in that: contain each described extract of claim 7 to 9.
11, the pharmaceutical composition of treatment hemorrhage according to claim 10, it is characterized in that: it is to be active component by each described extract of claim 7 to 9, adds the preparation that pharmaceutically acceptable carrier or complementary composition are prepared from.
12, pharmaceutical composition according to claim 11 is characterized in that: its dosage form is an oral formulations.
13, the purposes of each described extract of claim 7 to 9 in the medicine of preparation treatment hemorrhage.
14, the purposes of the described pharmaceutical composition of claim 11 in the medicine of preparation treatment hemorrhage.
15,, it is characterized in that described hemorrhagic disease is the department of obstetrics and gynecology hemorrhages according to the purposes of claim 1.
16, according to the purposes of claim 15, it is characterized in that: described department of obstetrics and gynecology hemorrhage is gynecological's menorrhagia, postpartum hemorrhage, and dysfunctional uterine hemorrhage become a mandarin or medicine stream postoperative hemorrhage, or intrauterine device causes metrorrhagia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03117694 CN1241618C (en) | 2003-04-15 | 2003-04-15 | Application of Ypsilandra herbs for preparing medicines for treating hemorrhagic diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03117694 CN1241618C (en) | 2003-04-15 | 2003-04-15 | Application of Ypsilandra herbs for preparing medicines for treating hemorrhagic diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1537570A CN1537570A (en) | 2004-10-20 |
| CN1241618C true CN1241618C (en) | 2006-02-15 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03117694 Expired - Lifetime CN1241618C (en) | 2003-04-15 | 2003-04-15 | Application of Ypsilandra herbs for preparing medicines for treating hemorrhagic diseases |
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| Country | Link |
|---|---|
| CN (1) | CN1241618C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1918973B (en) * | 2006-09-05 | 2010-06-02 | 红河千山生物工程有限公司 | Artificial breeding method for common forkstamenflower |
| CN101473792B (en) * | 2009-01-23 | 2011-04-06 | 中国科学院昆明植物研究所 | Tissue culture of Ypsilandra thibetica and planting method |
| CN105994552A (en) * | 2016-08-12 | 2016-10-12 | 安徽燕之坊食品有限公司 | Coarse cereal biscuits for preventing and treating hemorrhagic diseases and making method thereof |
| CN112656888A (en) * | 2020-12-31 | 2021-04-16 | 云南中医药大学 | Application of Aconitum Carmichaeli Debx in functional uterine bleeding |
-
2003
- 2003-04-15 CN CN 03117694 patent/CN1241618C/en not_active Expired - Lifetime
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| Publication number | Publication date |
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| CN1537570A (en) | 2004-10-20 |
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