CN101336997A - Medicine for hemorrhage after drug abortion - Google Patents

Medicine for hemorrhage after drug abortion Download PDF

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CN101336997A
CN101336997A CNA2008101352905A CN200810135290A CN101336997A CN 101336997 A CN101336997 A CN 101336997A CN A2008101352905 A CNA2008101352905 A CN A2008101352905A CN 200810135290 A CN200810135290 A CN 200810135290A CN 101336997 A CN101336997 A CN 101336997A
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parts
radix
medicine
extract
angelicae sinensis
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CN101336997B (en
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曹龙祥
刘昭阳
李昌龙
田刚
杨学芳
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Jumpcan Pharmaceutical Group Co., Ltd.
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JIANGSU JUMPCAN MEDICINES CO Ltd
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Abstract

The invention provides a medicament for treating hemorrhage after drug abortion, the preparation method and the application thereof. The medicament comprises the following basic materials by the weight part: 0.5 to 1.5 parts of notoginseng, 2 to 3 parts of milkvetch root, 1.5 to 2.5 parts of radix codonopsitis, 1.5 to 2.5 parts of rehmannia root, 1.5 to 2.5 parts of peach seed, 1.5 to 2.5 parts of angelica root, 1.5 to 2.5 parts of herba leonuri, 1.5 to 2.5 parts of indian madder root, 1.5 to 2.5 parts of himalayan teasel root, 3 to 5 parts of cuttlebone and 1.5 to 2.5 parts of caulis sargentodoxae. The medicament has good curative effects on hemorrhage, particularly after drug abortion, artificial abortion or parturition, or hemorrhage caused by lochiorrhagia and placenta retension after childbirth or abortion.

Description

A kind of medicine that is used for hemorrhage after drug abortion
Technical field
The invention provides a kind of medicine that is used for hemorrhage after drug abortion, and its production and use.Described medicine calculates by weight, comprise following principal agent: 0.5~1.5 part of Radix Notoginseng, 2~3 parts of the Radixs Astragali, 1.5~2.5 parts of Radix Codonopsis, 1.5~2.5 parts of Radix Rehmanniae, 1.5~2.5 parts in Semen Persicae, 1.5~2.5 parts of Radix Angelicae Sinensis, 1.5~2.5 parts of Herba Leonuris, 1.5~2.5 parts in Radix Rubiae, 1.5~2.5 parts of Radix Dipsacis, 3~5 parts of Endoconcha Sepiaes, 1.5~2.5 parts of Caulis Sargentodoxae.Medicine is to hemorrhage especially gynecological medicine stream, artificial abortion or divide the puerperium hemorrhage or postpartum lochiorrhea, retention of placenta or induced abortion cause hemorrhagely has a good therapeutical effect.Belong to field of medicaments.
Background technology
Medicine stream back vaginal hemorrhage is one of department of obstetrics and gynecology common clinical, frequently-occurring disease and difficult disease with the passing of time not to the utmost, is mainly seen in the women of period of duration age bracket.This disease has big hazardness to patient's physical and mental health, if untimely healing, with the passing of time delay can cause Abwehrkraft des Koepers and descend various disease conditions such as secondary infection, heating, stomachache, anemia.According to statistics, China therefore loses thousands of work, living and studying day every year, and ten hundreds of patients is worried for it, also every thorny for it and puzzlement of doctor that makes.China achieves success from the synthetic and production of mifepristone, and to being accepted by the early pregnancy women, year historical surplus in the of existing ten, this medicine is with its safe and effective characteristics, and it is clinical to be widely used in family planning, and its success rate of miscarrying can reach 90~95%.But the drawback that is difficult to overcome is arranged also, vaginal hemorrhage overlong time after many people's termination of pregnancy, amount of bleeding is many.To this, though in constantly being subjected to, doctor trained in Western medicine department of obstetrics and gynecology medical personnel's attention and concern, the treatment experience has accumulation repeatly, still is in present situation indivedual, that disperse, lack systematic study and produce effects medicine at present.Adopt antiinflammatory, hemostasis, contraction uterus or antifibrinolytic agent treatment, all difficulty is proved effective, and often needs the clearing heat in the pericardium to handle, and brings the secondary misery to the patient.Therefore, relevant this sick etiology and pathogenesis, therapy and formula are inquired into, and the research of especially using the Chinese medicine and pharmacy method day by day becomes the focus that vast medical scientific research worker selects a topic.People expect that a kind of determined curative effect, effect consolidation, safety non-toxic, the new Chinese medicine preparation of being convenient to take and carry succeed in developing, thereby remove the puzzlement that this illness is brought to people, be extensive patients work, life, study and healthy new medicine and the approach of bringing.
Summary of the invention
The present invention is under Chinese medical theory instructs, at gynecological's medicine stream, artificial abortion or the branch puerperium is hemorrhage or postpartum lochiorrhea, retention of placenta or induced abortion cause hemorrhage main etiology and pathogenesis and clinical characters, according to the principles of formulating prescriptions of the modern pharmacology of Chinese medical formulae, provide a kind of safe, specific hemorrhage medicine that is used for.
Technical scheme of the present invention is as follows:
The invention provides a kind of medicine that is used for hemorrhage after drug abortion, calculate by weight, comprise following principal agent: 0.5~1.5 part of Radix Notoginseng, 2~3 parts of the Radixs Astragali, 1.5~2.5 parts of Radix Codonopsis, 1.5~2.5 parts of Radix Rehmanniae, 1.5~2.5 parts in Semen Persicae, 1.5~2.5 parts of Radix Angelicae Sinensis, 1.5~2.5 parts of Herba Leonuris, 1.5~2.5 parts in Radix Rubiae, 1.5~2.5 parts of Radix Dipsacis, 3~5 parts of Endoconcha Sepiaes, 1.5~2.5 parts of Caulis Sargentodoxae.
Described Radix Notoginseng can be the dry root of panax araliaceae plant Panax notoginseng (Burk.) F.H.Chen.The described Radix Astragali can be the dry root of leguminous plant Radix Astagali Astragalus membranaceus (Fisch.) Bge.var.mongho-licus (Bge.) Hsiao or Radix Astragali Astragalus membranaceus (Fisch.) Bge..The preferred Radix Astragali Preparata that adopts for the process of preparing Chinese medicine processed goods of the Radix Astragali, is got astragalus mongholicus tablet, fries to tack-free according to processed with honey method (an appendix II of 2000 editions Chinese Pharmacopoeias D).Described Radix Codonopsis can be the dry root of campanulaceae plant Radix Codonopsis Codonopsis pilosula (Franch.) Nannf., plain flower Radix Codonopsis Codonopsispilosula Nannf.var.modesta (Nannf.) L.T.Shen or radix codonpsis tangshen Codonopsistangshen Oliv..Described Radix Rehmanniae can be the fresh or dried root of scrophulariaceae rehmannia glutinosa plant Rehmannia glutinosa Libosch..The preferred Radix Rehmanniae Preparata that adopts is the process of preparing Chinese medicine processed goods of Radix Rehmanniae.Concocting method can for: (1) gets clean Radix Rehmanniae, stewes to wine according to stewed with wine method (appendix II D) to exhaust, and takes out, and dry in the sun when dried slightly, is cut sheet or piece to the crust mucus, drying, promptly.Every 100kg Radix Rehmanniae is with yellow wine 30~50kg.(2) get clean Radix Rehmanniae, to black profit, take out, when solarization is done to about eighty per cant, cut sheet or piece according to steaming method (appendix II D) steaming, drying, promptly.Described Semen Persicae can be the dry mature seed of rosaceous plant peach Prunus persica (L.) Batsch or mountain peach Prunus davidiana (Carr.) Franch..Described Radix Angelicae Sinensis can be the dry root of umbelliferae angelica Angelica sinensis (Oliv.) Diels, preferably adopts the Radix Angelicae Sinensis that autumn end excavates, and removes fibrous root and silt, treat that moisture evaporates slightly after, tie into wisp, last canopy is with pyrotechnics smoke-dried beancurd slowly.Described Herba Leonuri can be the fresh or dry aerial parts of labiate Herba Leonuri Leonurus japonicusHoutt..Described Radix Rubiae can be the dry root and rhizome of Maguireothamnus speciosus Radix Rubiae Rubiacordifolia L..Described Radix Dipsaci can preferably adopt the Radix Dipsaci of excavating autumn for the dry root of Dipsacaceae plant Radix Dipsaci Dipsacusasperoides C.Y.Cheng et T.M.Ai, remove root head and fibrous root, to half-dried, bank up " diaphoresis " during to inner virescence with low baking temperature baking, oven dry again.Described Endoconcha Sepiae can be the dry inner shell of Sepiidae animal sepiella maindroni de Rochebrune Sepiella maindroni de Rochebrune or golden cuttlefish Sepiaesculenta Hoyle.Described Caulis Sargentodoxae can be the dry rattan of Lardizabalaceae plant Sargentodoxa cuneata (Oliv.) Rehd.et Wils..
Wherein, as preferred version, medicine of the present invention calculates by weight, comprises following principal agent: 1 part of Radix Notoginseng, 2.5 parts of the Radixs Astragali, 2 parts of Radix Codonopsis, 2 parts of Radix Rehmanniae, 2 parts in Semen Persicae, 2 parts of Radix Angelicae Sinensis, 2 parts of Herba Leonuris, 2 parts in Radix Rubiae, 2 parts of Radix Dipsacis, 4 parts of Endoconcha Sepiaes, 2 parts of Caulis Sargentodoxae.
Above-mentioned medicine can be made the pharmaceutical preparation that is fit to clinical practice by pharmaceutical technologies such as various extraction separation.For example, medicinal raw material is pulverized the preparation with the former powder form of crude drug, as tablet, capsule or various pills etc., also can be that the medical material decocting boils into decoction or oral liquid or syrup etc.
Wherein, as the preferred embodiment for the present invention, described medicine is the medicine for preparing by the method that comprises following steps:
(1) Radix Angelicae Sinensis extracts volatile oil;
(2) Radix Notoginseng obtains alcohol extract with 40%~95% ethanol extraction;
(3) Radix Notoginseng medicinal residues and all the other principal agents of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) obtain water extract with water extraction;
(4) water extract that obtains of the volatile oil that obtains of step (1), alcohol extract that step (2) obtains and step (3) mixes.
Wherein, in the described step (1), Radix Angelicae Sinensis can be by the method extraction volatile oil wherein of various in the art extraction volatile oil, for example milling process, steam distillation etc.
Wherein, in the described step (2), Radix Notoginseng is used pure soluble solvent, for example the mixed solvent of methanol, ethanol, isopropyl alcohol, acetone or itself and water extracts pure dissolubility effective ingredient wherein, as preferably, use ethanol water as extracting solvent, more preferably with 40%~95% ethanol as the extraction solvent.Extracting method can be extraction, percolation, heating extraction (as decocting method or reflux extraction) etc.
Wherein, in the described step (3), medicinal residues, step (2) Radix Notoginseng that step (1) Radix Angelicae Sinensis extracts behind the volatile oil are extracted the medicinal residues behind the alcohol extract, obtain water extract with all the other principal agents with water extraction.After each medical material can extract separately the extract merging is obtained water extract, also can mixed extraction obtain water extract.The present invention preferably obtains water extract with described medicinal residues and all the other principal agent waters mixing decoction extraction.
Wherein, in the described step (4), the mixing of each extract can be passed through the ordinary skill in the art.For example step (2) and (3) resulting extract are dried to dried cream, mix with described volatile oil again.Wherein, volatile oil is preferably made solid form and is mixed, and for example makes the Benexate Hydrochloride form of volatile oil by inclusion technique.
Wherein, as more preferably embodiment of the present invention, described medicine is the medicine for preparing by the method that comprises following steps:
(1) Radix Angelicae Sinensis extracts volatile oil with steam distillation.
(2) Radix Notoginseng makes alcohol extract with 50%~70% alcohol reflux.
(3) the Radix Notoginseng medicinal residues of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) mix the back and use water boiling and extraction with all the other principal agents, and extracting solution mixes with aqueous extract after step (1) is distilled, makes water extract.
(4) water extract that obtains of the volatile oil that obtains of step (1), alcohol extract that step (2) obtains and step (3) mixes.
Wherein, if desired, above-mentioned described medicine, step (3) also can comprise carries out precipitate with ethanol with aqueous extract, for example preferably adds ethanol and precipitates to containing alcohol amount 50%~80%, and filtrate recycling ethanol makes water extract.
Wherein, described steam distillation has no particular limits.The Radix Angelicae Sinensis medical material soaked 15~75 minutes, preferred 30~60 minutes with 4~15 times of water gagings, preferred 4~8 times of water gagings, and vapor distillation extracted 1~6 hour, preferred 2~4 hours.Aqueous solution after the distillation and medicinal residues stay does next step extraction separation usefulness.
For preventing to extract the loss of the Radix Angelicae Sinensis volatile oil that obtains, and cover the abnormal smells from the patient of Radix Angelicae Sinensis volatile oil, the present invention preferably adopts beta-schardinger dextrin-that it is carried out enclose.Volatile oil: beta-schardinger dextrin-(ml: be 1: 2~10 g), preferred volatile oil: beta-schardinger dextrin-(ml: be 1: 4~8 g); 40~70 ℃ of enclose temperature, preferred 50~65 ℃; Radix Angelicae Sinensis volatile oil is splashed in the beta-schardinger dextrin-solution, and the limit edged stirs, and stirs preferred 30~60 minutes 15~90 minutes, rotating speed is 150~250 rev/mins, 0~10 ℃ of cold preservation 10~15 hours, sucking filtration, oven drying at low temperature grinds standbyly, promptly gets the Radix Angelicae Sinensis volatile oil beta cyclodextrin inclusion complex.
Wherein, described ethanol reflux extraction also has no particular limits.Normal conditions, reflux, extract, 2~4 times, each 1~3 hour.Behind the resulting ethanol extract decompression recycling ethanol, drying under reduced pressure obtains the alcohol extract dried cream powder after the pulverizing again, and is standby.
Wherein, described water boiling and extraction method also has no particular limits.Normal conditions, 6~15 times of amount of water decoct and extract each 0.5~3 hour 1~3 time.Merge resulting aqueous extract, and merge, be concentrated into an amount of with aqueous solution that the Radix Angelicae Sinensis vapor distillation extracts behind the volatile oil.The present invention preferably adds aqueous extract ethanol and carries out precipitate with ethanol to containing alcohol amount 50%~90%, preferred 50%~85%, more preferably 60%~80%, get decompression filtrate recycling ethanol after, the concentrating under reduced pressure drying is pulverized the back and become the water extract dried cream powder, and is standby.
Wherein, in the described step (4), preferably above-mentioned prepared Radix Angelicae Sinensis volatile oil Benexate Hydrochloride, alcohol extract dried cream powder and water extract dried cream powder are mixed, obtain medicine of the present invention.
Wherein, above-mentioned described medicine if desired, also comprises one or more pharmaceutically conventional adjuvant.For example, make tablet, add filler, binding agent, lubricant or correctives etc. as required.For a person skilled in the art,, choose needed dosage form, select for use conventional pharmaceutical necessities to make suitable medicament, belong to conventional, general technology according to preparation and clinical needs.
The present invention also provides a kind of method for preparing above-mentioned described medicine, it is characterized in that comprising following steps:
(1) Radix Angelicae Sinensis extracts volatile oil;
(2) Radix Notoginseng obtains alcohol extract with 40%~95% ethanol extraction;
(3) the Radix Notoginseng medicinal residues of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) and all the other principal agent water extraction if desired, precipitate resulting extracting solution with 50%~80% ethanol, and filtrate recycling ethanol makes water extract;
(4) water extract that obtains of the volatile oil that obtains of step (1), alcohol extract that step (2) obtains and step (3) mixes.
Wherein, the technological parameter of above-mentioned described each step can be according to aforesaid technology.
As the preferred embodiment for the present invention, above-mentioned described method is characterized in that comprising following steps:
(1) Radix Angelicae Sinensis extracts volatile oil with steam distillation;
(2) Radix Notoginseng obtains alcohol extract with 50%~70% alcohol reflux;
(3) the Radix Notoginseng medicinal residues of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) and all the other principal agent water extraction, aqueous extract after the distillation of extracting solution and step (1) mixes, and if desired, also resulting extracting solution can be precipitated with 50%~80% ethanol, filtrate recycling ethanol makes water extract;
(4) water extract that obtains of the volatile oil that obtains of step (1), alcohol extract that step (2) obtains and step (3) mixes.
Wherein, the technological parameter of above-mentioned described each step can be according to aforesaid technology.
As one of preferred embodiment of the present invention, provide a kind of and be used for medicine stream, artificial abortion or divide hemorrhage medicine of puerperium, calculate by weight, comprise following principal agent: 1 part of Radix Notoginseng, 2.5 parts of Radix Astragali Preparatas, 2 parts of Radix Codonopsis, 2 parts of Radix Rehmanniae Preparata, 2 parts in Semen Persicae, 2 parts of Radix Angelicae Sinensis, 2 parts of Herba Leonuris, 2 parts in Radix Rubiae, 2 parts of Radix Dipsacis, 4 parts of Endoconcha Sepiaes, 2 parts of Caulis Sargentodoxae, it makes granule by the method that comprises following steps:
(1) Radix Angelicae Sinensis extracts volatile oil with steam distillation;
(2) Radix Notoginseng is with 50%~70% alcohol reflux, and drying under reduced pressure made the alcohol extract dried cream powder after extracting solution reclaimed ethanol;
(3) the Radix Notoginseng medicinal residues of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) and all the other principal agent water boiling and extraction, aqueous extract after the distillation of extracting solution and step (1) mixes, reuse 50%~80% ethanol precipitates, and drying under reduced pressure makes the water extract dried cream powder behind the filtrate recycling ethanol;
(4) volatile oil that step (1) is obtained, the water extract that alcohol extract that makes with step (2) and step (3) make mixes, and adds adjuvant, granulates into granule.
Wherein, as preferably, described volatile oil is made remix behind the volatile oil beta cyclodextrin inclusion complex with beta-schardinger dextrin-; As preferably, described adjuvant is selected from filler such as sucrose, dextrin, starch, microcrystalline Cellulose, mannitol, lactose etc. one or more and correctives such as aspartame or steviosin etc.; As preferably, described granulation uses 0%~30%PVP alcoholic solution as binding agent, and wherein said ethanol is that concentration is the ethanol water of 60%-100%.
Wherein, the technology in above-mentioned per step can be according to above-mentioned described parameter.
The above-mentioned described medicine of the present invention, have the hemorrhage especially gynecological of outstanding treatment medicine stream, artificial abortion or divide the puerperium hemorrhage or that postpartum lochiorrhea, retention of placenta or induced abortion cause is hemorrhage, can be used for preparing the hemorrhage especially gynecological of treatment medicine stream, artificial abortion or divide the hemorrhage medicine that the puerperium is hemorrhage or postpartum lochiorrhea, retention of placenta or induced abortion cause.For example, medicine of the present invention has and reduces medicine stream rat uterus amount of bleeding due to mifepristone and the misoprostol, promote the effect that repair in the miscarriage uterus, the uterine smooth muscle contraction of rabbit has potentiation to puerperal, the effect that messenger drug stream clotting time of mice and normal mouse bleeding time shorten, it can also impel the contraction of uterine vascular, and the flesh layer is thickened become fine and close, thereby reach the hemostatic effect, inhibited to placing due to the foreign body inflammation in the rat uterus, also have certain analgesic activity etc.
The above-mentioned described medicine of the present invention, clinical practice safety, untoward reaction is little.313 multiple doses by the clinical consumption that is equivalent to be grown up are given mouse stomach, and during the administration, mice outward appearance, behavioral activity body weight, feed, defecation are normal, none dead mouse.The safety range that proves this medicine is bigger.Dosage is heavy dose of group 126.0g crude drug/kg, middle dosage group 63.0g crude drug/kg, small dose group 31.5g crude drug/kg, 62.6 times, 31.3 times and 15.6 times of clinical consumption are equivalent to respectively to be grown up, each organizes 13 weeks of rat successive administration, after 45 days, 90 days and drug withdrawal after the administration, observed in 4 weeks respectively, blood biochemical learns index and the concurrent control group compares, difference that there are no significant, result are within normal fluctuation range, and obvious change does not take place hematological indices; Rat outward appearance, behavior, activity, body weight, feed, defecation are normal, and 18 kinds of internal organs and tissue are carried out pathologic finding, there is no drug-induced pathomorphology damage, prove that medicine of the present invention does not have the overt toxicity effect to rat.
The specific embodiment
Further explain and describe the present invention by the following examples, but do not constitute limiting the scope of the invention.
Embodiment 1
Radix Astragali Preparata 500g, Radix Notoginseng 200g, Radix Codonopsis 400g, Radix Rehmanniae Preparata 400g, Semen Persicae 400g, Radix Angelicae Sinensis 400g, Herba Leonuri 400g, Radix Rubiae 400g, Radix Dipsaci 400g, Endoconcha Sepiae 800g, Caulis Sargentodoxae 400g.Wherein:
(1) Radix Angelicae Sinensis adds 4 times of amounts of water, soaks 1 hour, carries volatile oil 4 hours with steam distillation, and the lixiviating solution after volatile oil and distillation device is in addition collected;
(2) Radix Notoginseng adds 60% alcohol reflux twice, adds 7 times of amounts of alcohol for the first time, adds 5 times of amounts, each 1.5 hours for the second time, merge alcohol extract, filter, decompression filtrate recycling ethanol to relative density is 1.08-1.10 (60 ℃), drying under reduced pressure is pulverized, and gets Radix Notoginseng alcohol extraction dried cream powder;
(3) Radix Notoginseng, Radix Angelicae Sinensis medicinal residues and all the other medical materials decoct with water and extract 3 times, add 10 times of amounts of water at every turn and decoct 2 hours, filter, filtrate and Radix Angelicae Sinensis water extract merge, being evaporated to relative density is the clear paste of 1.15-1.20 (60 ℃), adds 95% ethanol and makes and contain alcohol amount and reach 60%, leaves standstill 24 hours, filter, decompression filtrate recycling ethanol, being concentrated into relative density is the clear paste of 1.20-1.30 (60 ℃), drying under reduced pressure becomes dried cream, pulverize, get water and carry dried cream powder;
(4) get step (1) volatile oil and cycloheptaamylose, volatile oil: cycloheptaamylose: water is 1: 8: 90 (W: W: V), cycloheptaamylose is added in the entry, be warming up to 65 ℃, under 200r/min stirs, slowly drip volatile oil, added behind the volatile oil 65 ℃ of insulated and stirred 1 hour, 4 ℃ of cold preservation 12 hours is filtered, and precipitates 40 ℃ of oven dry, grind standby, volatile oil cycloheptaamylose clathrate.Get above-mentioned Radix Notoginseng alcohol extraction dried cream powder, water is carried dried cream powder, volatile oil cycloheptaamylose clathrate, adds dextrin, aspartame, granulate with the 20%PVP alcoholic solution, 60 ℃ of dryings, granulate is made granule 1000g, promptly.
Embodiment 2: to rat medicine stream back metrorrhagia amount and the in utero influence of film form
1, medicine
Medicine dried cream powder of the present invention: make according to the foregoing description 1 method, do not add adjuvants such as dextrin, aspartame.Every gram dried cream powder is equivalent to crude drug 7.50g.
Positive control drug: GONGXUENING JIAONANG: 0.13g/ grain, Yunnan Paiyao Group Corp., Ltd's product, lot number: 20031002.
Mifepristone sheet: 25mg/ sheet, Zizhu Pharmaceutical Co., Ltd., Beijing's product, lot number: 43041001.
Misoprostol sheet: 0.2mg/ sheet, Zizhu Pharmaceutical Co., Ltd., Beijing's product, lot number: 41030409.
2, method
Rat is mated copulation, continuous 4 days in female, male 2: 1 ratios.Carry out vaginal smear examination morning every day, will have the female Mus of sperm to take out, and as the 1st day (d1) of gestation.Random packet is raised by date.Totally 70 of pregnant rats are divided into 6 groups: 11 of normal pregnancy groups, 12 of model group, 11 of positive controls, medicine of the present invention is little, in, each 12 of heavy dose of groups.In addition, get 10 not the female Mus of copulation as the blank group.Except that normal pregnancy group and blank group, all the other respectively organize rat in gestation the 7th day at 8 o'clock in (d7) morning and at 6 o'clock in afternoon irritate respectively the stomach mifepristone (0.83mg/ml, 1ml/100g, 8.3mg/kg) and misoprostol (10 μ g/ml, 1ml/100g, 100 μ g/kg); Normal pregnancy group, blank group are then irritated stomach and are given isopyknic distilled water.Simultaneously insert one of quantitative sterilized cotton ball (the heavy 85-90mg of cotton balls, half side, leak outside and urine is backflowed) with resistant to blood with the plastic sheeting parcel in intravaginal.Put into plastic bag airtight stored refrigerated respectively at 8 o'clock in the morning and at 6 o'clock in afternoon cotton balls being taken out next day, replaces a new cotton balls simultaneously in intravaginal, is operated to the 14th day (d14) more than continuously.
Each organizes beginning next day (d8) gastric infusion after modeling.Medicine of the present invention is little, in, heavy dose of group irritates stomach respectively and gives the medicine dried cream powder suspension of the present invention that concentration is 0.087g/ml, 0.174g/ml and 0.348g/ml, the administration volume is 1ml/100g, and dosage is respectively 6.53g crude drug/kg, 13.05g crude drug/kg, 26.10g crude drug/kg (be equivalent to respectively be grown up clinical consumption 3.2,6.5 and 13.0 times); Positive controls is irritated stomach and is given GONGXUENING suspension 0.007g/ml, and the administration volume is 1ml/100g, and dosage is 0.07g/kg (is equivalent to be grown up clinical consumption 6.5 times).Once a day, continuous 7 days.Normal pregnancy group, blank group are irritated stomach and are given the equal-volume distilled water.
24h after the last administration, puts to death then and respectively organizes rat in tail vein blood 0.02ml with hemoglobin straw.Cut open the belly, take out the uterus, use 10% formaldehyde fixed.The rat vagina cotton balls of collecting is carried out amount of bleeding to be measured.
3, metrorrhagia quantitative determination:
Tail vein 0.02ml adds 5%NaOH solution 4ml, and mixing is stand-by.The uterus cotton balls of collecting is placed respectively in the beaker, soak extruding with 5%NaOH solution 15ml and wash the cotton balls bloodstain by rubbing with the hands, get the 5ml lixiviating solution and filter.With filtering lixiviating solution 4ml, rat tail vein blood 5%NaOH solution 4ml, be blank respectively, in ultraviolet-uisible spectrophotometer 546nm wavelength place record absorbance A value with 5%NaOH solution.Metrorrhagia amount metering formula:
Figure A20081013529000131
The V1=dilution used 5%NaOH amount of tail vein (4ml);
The used 5%NaOH amount of V2=lixiviate uterus blood (15ml)
4, result
(1) to the influence of early pregnancy rat uterus amount of bleeding.The results are shown in Table 1.
Table 1 is respectively organized the variation of rat uterus amount of bleeding
Annotate: compare with the normal pregnancy group: *P<0.01;
Compare with model group: #P<0.05, ##P<0.01;
Compare with positive controls: ◇ ◇ P<0.01;
Compare with small dose group: △ P<0.05, △ △ P<0.01
Compare with middle dosage group: ▲ P<0.05
As can be seen from Table 1, the metrorrhagia amount of model group rat far away more than the normal pregnancy group (normal pregnancy group, blank group are collected because of uterus secretions is arranged, and uterus secretions is faint yellow, colourless not to be waited, thus wash soak the back colorimetric certain reading is arranged).Compare with model group, the metrorrhagia amount of dosage group, heavy dose of group obviously reduces in positive controls, the medicine of the present invention; And small dose group does not have the significance variation.The metrorrhagia amount of the heavy dose of group of medicine of the present invention obviously is less than positive controls.Compare between three dosage groups: middle dosage group, heavy dose of group obviously are less than small dose group; And heavy dose of group obviously is less than middle dosage group, is certain dosage and relies on trend.
(2) to the influence of uterus shape afterwards of rat medicine stream
Observed result under light microscopic:
The blank group: cavity of uterus is not expanded, and it is complete to be answered epithelium.Interior membrane structure is normal, visible normal distribution body of gland.The inner membrance Interstitial cell does not have hypertrophy.Inside and outside flesh layer muscle fiber traveling and thickness are normal.Blood vessel does not have dilatation and congestion between mesentery and flesh.
Normal pregnancy group: see the fetal tissues group in the cavity of uterus.Embryo development is normal, and Placenta Hominis physically well develops.Amniotic membrane, umbilical cord, chorion frondosum, decidua basalis are all high-visible.The normal Uterus wall of outer vertical interior circular muscle is thin.The equal dilatation and congestion of blood vessel in mesentery, flesh layer and the inner membrance.
Model group: uterine cavity is obviously expanded, visible more residual, regression, necrosis, disintegrate decidua tissue and with hemorrhage.Vasodilation hyperemia in mesentery, flesh layer and the inner membrance.The flesh layer is than normal thin.
Positive controls: uterine cavity still more normally enlarges, but the holomorphosis of inner membrance major part, covering epithelium is complete.Reach epithelial surface in the uterine cavity place's visible small amount of residual gestation tissue is arranged.Vasodilation hyperemia is not obvious in mesentery, flesh layer and the inner membrance.It is more normal that the flesh layer recovers.
Heavy dose of group: uterine cavity is not expanded, and not seeing has residual pregnant thing.Inner membrance regeneration is complete, and covering epithelium, inner membrance body of gland and flesh layer are similar with normal uterus.Blood vessel is not seen dilatation and congestion in mesentery, flesh layer and the inner membrance.The outer longitudinal muscle fiber alignment of internal ring is neat, and densification is with the normal uterus zero difference.
Middle dosage group: the uterine cavity expansion is not obvious, is answered epithelium to have repaired complete.The holomorphosis of inner membrance major part, accidental a small amount of special mess shape is organized regression.Blood vessel is not seen dilatation and congestion in mesentery, flesh layer and the inner membrance.It is normal that the flesh layer recovers.
Small dose group: uterine cavity expansion.Endometrium regeneration not exclusively has the still visible residual regression decidua tissue in place.Blood vessel is located still dilatation and congestion in mesentery, flesh layer and the inner membrance.The flesh layer is than normal thin.
(3) to the influence of artery and vein external caliber area in the mesometrium of rat medicine stream back, the results are shown in Table 2.
Table 2 is respectively organized the variation of artery and vein external caliber area in the rat uterus mesentery
Figure A20081013529000151
Annotate: compare with the blank group: *P<0.05, *P<0.01;
Compare with model group: #P<0.05, ##P<0.01;
Compare with small dose group: △ P<0.05, △ △ P<0.01
As can be seen from Table 2, the interior external caliber area of artery and vein is higher than other each group far away in normal pregnancy rat uterus mesentery and the flesh layer, and this is because a kind of normal physiological reaction of body in order to provide sufficient nutrition to produce to the embryo.
As shown in Table 2, artery and vein external caliber area is significantly higher than the blank group in the model group mesentery.With model group relatively, in positive controls, the medicine of the present invention, artery and vein external caliber area obviously reduces in heavy dose of group mesentery, and the small dose group there was no significant difference.Between three dosage groups relatively: there was no significant difference between three groups of the arteries bore areas; Vein blood vessel bore area, in, heavy dose of group is starkly lower than small dose group, and there was no significant difference between middle dosage group and heavy dose of the group.
(4) to the influence of artery and vein external caliber area in rat medicine stream back uterine smooth muscle thickness and the flesh layer, the results are shown in Table 3.
Table 3 is respectively organized the variation of artery and vein external caliber area in rat uterus smooth muscle thickness and the flesh layer
Figure A20081013529000152
Annotate: compare with the blank group: *P<0.05, *P<0.01;
Compare with model group: #P<0.05, ##P<0.01;
Compare with positive controls: ◇ P<0.05;
Compare with small dose group: △ P<0.05, △ △ P<0.01
As can be seen from Table 3, normal pregnancy group rat uterus smooth muscle thickness significantly reduces than the blank group, and this is owing to due to embryo's the compressing, be a kind of normal physiological reaction.The uterine smooth muscle thickness of model group significantly reduces than the blank group.With model group relatively: in positive controls, the medicine of the present invention, the uterine smooth muscle thickness of heavy dose of group obviously increases, and the small dose group there was no significant difference.Between three dosage groups relatively: in, heavy dose of group is apparently higher than small dose group, and compare between heavy dose of group and the middle dosage group, though the trend of increase is arranged, there was no significant difference.
Artery and vein external caliber area significantly increases than the blank group in the model group flesh layer.With model group relatively: in the medicine of the present invention, artery and vein external caliber area all obviously reduces in heavy dose of group flesh layer; The arteries bore area of positive controls obviously reduces, though and vein has the trend of reduction, there was no significant difference; Small dose group is there was no significant difference then.Between three dosage groups relatively: in, heavy dose of group is starkly lower than small dose group, and there was no significant difference between heavy dose of group and the middle dosage group.
Above result shows: in the medicine of the present invention, heavy dose can make rat medicine stream back metrorrhagia amount significantly reduce, promote the involution of uterus, thereby reach the effect of curative stream back metrorrhagia; In addition, medicine of the present invention can also messenger drug in the stream rat uterus mesentery, flesh layer artery and vein external caliber area significantly dwindle, and the flesh layer thickness is obviously increased.This illustrates that this medicine can impel the contraction of uterine vascular, and the flesh layer is thickened become fine and close.
The present invention is described according to preferred embodiment.Should be understood that the description of front and embodiment are just to illustrating the present invention.Under prerequisite without departing from the spirit and scope of the present invention, those skilled in the art can design multiple alternative of the present invention and improvement project, and it all should be understood to be within protection scope of the present invention.

Claims (10)

1, a kind ofly is used for hemorrhage medicine, calculates by weight, make by following raw material: 0.5~1.5 part of Radix Notoginseng as principal agent, 2~3 parts of the Radixs Astragali, 1.5~2.5 parts of Radix Codonopsis, 1.5~2.5 parts of Radix Rehmanniae, 1.5~2.5 parts in Semen Persicae, 1.5~2.5 parts of Radix Angelicae Sinensis, 1.5~2.5 parts of Herba Leonuris, 1.5~2.5 parts in Radix Rubiae, 1.5~2.5 parts of Radix Dipsacis, 3~5 parts of Endoconcha Sepiaes, 1.5~2.5 parts of Caulis Sargentodoxae.
2, medicine according to claim 1 wherein, calculates by weight, is made by following raw material as principal agent: 1 part of Radix Notoginseng, 2.5 parts of the Radixs Astragali, 2 parts of Radix Codonopsis, 2 parts of Radix Rehmanniae, 2 parts in Semen Persicae, 2 parts of Radix Angelicae Sinensis, 2 parts of Herba Leonuris, 2 parts in Radix Rubiae, 2 parts of Radix Dipsacis, 4 parts of Endoconcha Sepiaes, 2 parts of Caulis Sargentodoxae.
3, according to the described medicine of claim 1-2, wherein, the preferred Radix Astragali Preparata of the described Radix Astragali, the preferred Radix Rehmanniae Preparata of described Radix Rehmanniae.
4,, it is characterized in that preparing by the method that comprises following steps according to the described medicine of claim 1-3:
(1) Radix Angelicae Sinensis extracts volatile oil.
(2) Radix Notoginseng obtains alcohol extract with 40%~95% ethanol extraction.
(3) Radix Notoginseng medicinal residues and all the other principal agents of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) obtain water extract with water extraction.
(4) water extract that obtains of the volatile oil that obtains of step (1), alcohol extract that step (2) obtains and step (3) mixes.
5, medicine according to claim 4 is characterized in that preparing by the method that comprises following steps:
(1) Radix Angelicae Sinensis extracts volatile oil with vapor distillation.
(2) Radix Notoginseng makes alcohol extract with 50%~70% alcohol reflux.
(3) the Radix Notoginseng medicinal residues of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) mix the back and use water boiling and extraction with all the other principal agents, and extracting solution mixes with aqueous extract after step (1) is distilled, makes water extract.
(4) water extract that obtains of the volatile oil that obtains of step (1), alcohol extract that step (2) obtains and step (3) mixes.
6, according to the described medicine of claim 4-5, it is characterized in that step (3) comprises that also aqueous extract is added ethanol to be precipitated to containing alcohol amount 50%~80%, filtrate recycling ethanol makes water extract.
7,, wherein, if desired, also comprise one or more pharmaceutically conventional adjuvant according to the described medicine of claim 1-6.
8, a kind of method for preparing the described medicine of claim 1-7 is characterized in that comprising following steps:
(1) Radix Angelicae Sinensis extracts volatile oil;
(2) Radix Notoginseng obtains alcohol extract with 40%~95% ethanol extraction;
(3) the Radix Notoginseng medicinal residues of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) and all the other principal agent water extraction if desired, precipitate resulting extracting solution with 50%~80% ethanol, and filtrate recycling ethanol makes water extract;
(4) water extract that obtains of the volatile oil that obtains of step (1), alcohol extract that step (2) obtains and step (3) mixes.
9, a kind of medicine stream, artificial abortion or branch hemorrhage medicine of puerperium of being used for calculates by weight, made by following raw material as principal agent: 1 part of Radix Notoginseng, 2.5 parts of Radix Astragali Preparatas, 2 parts of Radix Codonopsis, 2 parts of Radix Rehmanniae Preparata, 2 parts in Semen Persicae, 2 parts of Radix Angelicae Sinensis, 2 parts of Herba Leonuris, 2 parts in Radix Rubiae, 2 parts of Radix Dipsacis, 4 parts of Endoconcha Sepiaes, 2 parts of Caulis Sargentodoxae, it makes granule by the method that comprises following steps:
(1) Radix Angelicae Sinensis extracts volatile oil with steam distillation;
(2) Radix Notoginseng is with 50%~70% alcohol reflux, and drying under reduced pressure made the alcohol extract dried cream powder after extracting solution reclaimed ethanol;
(3) the Radix Notoginseng medicinal residues of the Radix Angelicae Sinensis medicinal residues of step (1), step (2) and all the other principal agent water boiling and extraction, aqueous extract after the distillation of extracting solution and step (1) mixes, reuse 50%~80% ethanol precipitates, and drying under reduced pressure makes the water extract dried cream powder behind the filtrate recycling ethanol;
(4) volatile oil that step (1) is obtained, the water extract that alcohol extract that makes with step (2) and step (3) make mixes, and adds adjuvant, granulates into granule.
Wherein, as preferably, described volatile oil is made remix behind the volatile oil beta cyclodextrin inclusion complex with beta-schardinger dextrin-; As preferably, described adjuvant is selected from filler such as sucrose, dextrin, starch, microcrystalline Cellulose, mannitol, lactose etc. one or more and correctives such as aspartame or steviosin etc.; As preferably, described granulation uses 0%~30%PVP ethanol (wherein said concentration of ethanol is 60%-100%) solution as binding agent.
10, aforesaid right requires the application of described medicine in the hemorrhage especially gynecological of preparation treatment medicine stream, artificial abortion or the branch medicine that the puerperium is hemorrhage or postpartum lochiorrhea, retention of placenta or induced abortion cause bleeding.
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CN102166317A (en) * 2011-04-22 2011-08-31 南阳理工学院 Traditional Chinese medicine combination for curing metrorrhagia and metrostaxis
CN102327395A (en) * 2011-10-11 2012-01-25 沙同叶 Pharmaceutical composition for treating postpartum persistent lochia and preparation method thereof
CN102727771A (en) * 2012-06-28 2012-10-17 贾丽丽 Traditional Chinese drug decoction for treating colporrhagia after artificial abortion
CN103301350A (en) * 2013-07-05 2013-09-18 张召菊 Traditional Chinese medicine for treating postpartum lochiorrhea
CN103908517A (en) * 2014-04-09 2014-07-09 于建敏 Compound medicine for preventing and treating postpartum hemorrhage
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CN102166317A (en) * 2011-04-22 2011-08-31 南阳理工学院 Traditional Chinese medicine combination for curing metrorrhagia and metrostaxis
CN102166317B (en) * 2011-04-22 2012-06-27 南阳理工学院 Traditional Chinese medicine combination for curing metrorrhagia and metrostaxis
CN102327395A (en) * 2011-10-11 2012-01-25 沙同叶 Pharmaceutical composition for treating postpartum persistent lochia and preparation method thereof
CN102327395B (en) * 2011-10-11 2013-03-20 沙同叶 Pharmaceutical composition for treating postpartum persistent lochia and preparation method thereof
CN102727771A (en) * 2012-06-28 2012-10-17 贾丽丽 Traditional Chinese drug decoction for treating colporrhagia after artificial abortion
CN103301350A (en) * 2013-07-05 2013-09-18 张召菊 Traditional Chinese medicine for treating postpartum lochiorrhea
CN103908517A (en) * 2014-04-09 2014-07-09 于建敏 Compound medicine for preventing and treating postpartum hemorrhage
CN103908517B (en) * 2014-04-09 2015-11-04 于建敏 A kind of compound medicine of prophylactic treatment postpartum hemorrhage
CN103933484A (en) * 2014-05-09 2014-07-23 李静 Traditional Chinese Medicine (TCM) capsule for treating postpartum persistent lochia
CN103933484B (en) * 2014-05-09 2016-04-06 李静 A kind ofly treat the more than Chinese medicinal capsule of lochia
CN106890242A (en) * 2017-03-16 2017-06-27 杨本雷 It is a kind of to treat pharmaceutical composition of irregular menstruation and preparation method thereof, preparation and application
CN112314912A (en) * 2020-11-01 2021-02-05 昆明理工大学 A steam pot soup with effect of promoting involution of uterus
CN114869949A (en) * 2022-05-26 2022-08-09 山西黄河中药有限公司 A pharmaceutical composition for treating puerperal diseases, and its preparation method

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