CN103071103B - Pregnancy healing oral liquid for treating abortion and preparation method of oral liquid - Google Patents
Pregnancy healing oral liquid for treating abortion and preparation method of oral liquid Download PDFInfo
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Abstract
The invention discloses a preparation technology of a pregnancy healing oral liquid. On the basis that the advantages of the original technology are reserved, the improved technology adopts fractionation first and then combined decoction. A preparation method particularly comprises the following steps that volatile oil in angelica sinensis, cuscuta chinensis, fructus corni, fructus amomi, alpiniaoxyphylla and folium artemisiae argyi is extracted with a steam distillation method; and medicine dregs and the rest 16 medicines (except donkey-hide gelatin) are decocted with the traditional method. According to the preparation technology, a ZTC1+1 natural clarifying agent replaces alcohol to remove unstable constituents and impurities in a water decocted liquid; the advantages of the original method are carried on; effective constituents of a whole prescription are reserved; the quality and the stability of the medicines are improved; the production cost is lowered; a production cycle is shortened; treatment effects of the medicines are ensured; and a cure rate of the medicines is increased. Steviosin serves as a sweetening agent for replacing cane sugar and honey; clinic adaptation population of the oral liquid is enlarged; and the oral liquid can reduce incidence of gestational diabetes effectively, and makes contributions to health of a mother and an infant.
Description
Technical field
The invention belongs to the field of Chinese medicines, the present invention relates to a kind of YUNKANG KOUFUYE for the treatment of miscarriage and preparation method thereof, be specifically related to the improvement of extraction and purification process in a kind of preparation method for the treatment of threatened abortion, habitual abortion YUNKANG KOUFUYE.
Background technology
Threatened abortion, habitual abortion are that gynecological is common and jeopardize difficult disease, clinically show as mainly that stomachache, vagina are bled on a small quantity, inferior belly gas pain, even can cause embryonic death and parent complication.In recent years, for various reasons, the sickness rate among the gravid woman of threatened abortion, habitual abortion is continuous ascendant trend, according to statistics, sickness rate is up to 12%, and not only health and the life security of fetus and parent in serious threat, brings greatly psychic pain for simultaneously patient and household thereof.Doctor trained in Western medicine is used the medicine of many control miscarriages, but curative effect can not be satisfactory, and the part medicine has serious adverse to fetus.The traditional Chinese medical science is defined as miscarriage " vaginal bleeding during pregnancy " " frequent fetal movement " " habitual abortion " " abortion " " abortion within the first month of pregnancy " categories such as " retention of dead fetus ".The traditional Chinese medical science think repeatly pregnant fall repeatly to hinder dash to appoint, so deficiency syndrome are seen more." deficiency syndrome should be treated by tonifying method " is that mainly executing of habitual abortion disease controlled principle, grasps the measure of " putting prevention first and combining prevention with control ", and the traditional Chinese medical science is advocated to answer kidney and spleen invigorating before the unpregnancy, and benefiting QI and nourishing blood transfers Gu Chong to appoint, and the treatment of should preventing miscarriage after the gestation obtains good curative effect.
YUNKANG KOUFUYE comes from peace emblem province Er Shan Yangshi secret prescription handed down in the family from generation to generation, function spleen benefiting and strengthen kidney, nourishing blood and preventing abortion.Be used for renal deficiency type and weak type of qi and blood threatened abortion and habitual abortion, continue to use through attacking mutually from generation to generation, have advantages such as determined curative effect, non-evident effect and application convenience." YUNKANG KOUFUYE " CN200810120726.3 is a kind of Chinese patent medicine of having sold.Be used for the treatment of suffer from a deficiency of the kidney gentle making a deficient case more deficient weak type tendency and habitual abortion since this medicine production always, obtain certain curative effect; But curative effect is not remarkable in the process of practical application, cure rate 60.46%.In recent years, we are on former side's basis, analyze reason from many aspects, grope by a large amount of experiments, prove that this side's prescription is scientific and reasonable, but because our medical material is formed complicated, having more than of drug effect of performance is single or the simple combination of several effective ingredient, but effective component group, so the selection of the extracting method of Chinese medicine should be by the requirement of Chinese medical theory and clinical effect, with reference to physicochemical property and the Pharmacological action study result of each medicine ingredient.The method of the extraction purification of continuing to use traditional " water extract-alcohol precipitation " of " YUNKANG KOUFUYE ", the drawback of " water extract-alcohol precipitation " method is to cause a lot of loss of active ingredients, causes this side's curative effect to reduce, and cure rate is low, the curative effect instability.The present invention fully uses modern science and technology and means in conjunction with the physicochemical property with reference to each medicine ingredient, carries out design and the screening of extracting method.
Also has other dosage form in the prior art, " a kind of method of preparation of pregnant recovering capsule " CN201110431749.8 as Jiangxi Jimin Kexin Drug Industry Co., Ltd's application is prepared from by following Chinese medicinal raw materials medicine: Colla Corii Asini 80-120 part, Rhizoma Dioscoreae 160-200 part, Radix Dipsaci 90-130 part, Radix Astragali 120-160 part, Radix Angelicae Sinensis 90-130 part, Rhizoma Cibotii 120-160 part, Semen Cuscutae 90-130 part, Herba Taxilli 50-90 part, Cortex Eucommiae 90-130 part, Fructus Psoraleae 90-130 part, Radix Codonopsis 90-130 part, Poria 120-160 part, Rhizoma Atractylodis Macrocephalae 90-130 part, Radix Rehmanniae 120-160 part, Fructus Corni 90-110 part, Fructus Lycii 120-160 part, Fructus Mume 50-90 part, Radix Paeoniae Alba 90-130 part, Fructus Amomi 50-90 part, Fructus Alpiniae Oxyphyllae 50-90 part, Radix Boehmeriae 90-130 part, Folium Artemisiae Argyi 5-20 part, Radix Scutellariae 50-90 part.This preparation method is prepared into capsule with former square tube simple excessively " decoction and alcohol sedimentation technique " with it, has the following disadvantages:
(1) we are made up of 23 flavor Chinese medicines, the prescription complexity, Chinese medicine ingredients complexity, drug effect are different, so take all factors into consideration Chinese medical theory and clinical requirement, physicochemical property and Pharmacological action study result with reference to each flavour of a drug ingredient carry out design and the screening of extracting method.The side of this preparation has adopted simple decocting cooking method, has ignored the difference of the chemical constituent of our Chinese crude drug, extraction ratio of effective constituents is lowered, and give filtration and refining making troubles, and water decoction easily goes mouldy.
(2) adopt 70% precipitation with alcohol to remove impurity in the extracting solution, this method is to flavone, polysaccharide, and saponin, the retention rate of effective ingredient such as alkaloid is low, and loss is big, and some effective ingredient (polysaccharide) of easily removing in the prescription is removed; Influence precipitate with ethanol factor complexity, operability and repeatability are relatively poor; Remove impurity is incomplete, with influencing the clarity of extracting solution, influences stability of formulation and drug effect simultaneously; This law consumption alcohol amount is big, and the cost price of said preparation is increased.
(3) we are made up of 23 flavor Chinese medicines, the prescription complexity, and composition is different, and our oral liquid uses generally at home, good effect.Change oral liquid into capsule, taking dose be one time 1, one day 3, every 0.3g.According to recipe quantity calculating every day, the said preparation dosage is few, does not reach effective therapeutic dose, clinical drug effect potentially unstable.
Summary of the invention
The invention provides a kind of YUNKANG KOUFUYE for the treatment of miscarriage and preparation method thereof.Thereby mainly provide a kind of preparation technology of new YUNKANG KOUFUYE by improved process, be intended to bring into play to a greater extent the curative effect of product, improve cure rate, guarantee the stability of product, select for use steviosin as sweeting agent place of sucrose and Mel simultaneously, it has enlarged clinical adaptation population, can effectively reduce the sickness rate of gestational diabetes, for baby's health is contributed.
One of technical solution of the present invention: a kind of YUNKANG KOUFUYE for the treatment of miscarriage, it is characterized in that being made as follows by following each bulk drugs: 115-130 parts of Rhizoma Dioscoreaes, 70-80 parts of Radix Dipsacis, 90-110 parts of the Radixs Astragali, 70-80 parts of Radix Angelicae Sinensis, 90-110 parts of Rhizoma Cibotii, 70-80 parts of Semen Cuscutae, 40-60 parts of Herba Taxillis, 70-80 parts of the Cortexs Eucommiae, 70-80 parts of Fructus Psoraleaes, 70-80 parts of Radix Codonopsis, 90-110 parts in Poria, 70-80 parts of the Rhizoma Atractylodis Macrocephalaes, 20-30 parts in Colla Corii Asini, 90-110 parts of Radix Rehmanniae, 70-80 parts of Fructus Corni, 90-110 parts of Fructus Lycii, 40-60 parts of Fructus Mumes, 70-80 parts of the Radix Paeoniae Albas, 40-60 parts of Fructus Amomis, 40-60 parts of Fructus Alpiniae Oxyphyllaes, 70-80 parts of Radix Boehmeriaes, 40-60 parts of Radix Scutellariaes, 5-15 parts of Folium Artemisiae Argyis;
(1) get recipe quantity Rhizoma Dioscoreae, the Radix Astragali, Radix Angelicae Sinensis, Fructus Psoraleae, Radix Codonopsis, Radix Scutellariae, the Radix Paeoniae Alba, Fructus Corni and Fructus Lycii with 50-60 ℃ of warm water soaking 3-6 hours, filter, filtrate for later use, filtering residue adds 6-10 times of water gaging and decocted 1-3 hour, gets medicinal liquid and medicinal residues;
(2) except Colla Corii Asini, all the other 13 flavors filtered with 50-60 ℃ of warm water soaking 3-6 hours, filtrate for later use, and filtering residue adds 6-10 times of water gaging and decocted 1-3 hour, gets medicinal liquid and medicinal residues;
(3) medicinal residues that decoct in the step (1) being remerged the medicinal residues that decoct in the step (2) adds water and fries in shallow oil secondary altogether, add for the first time filtrate in step (1) and the step (2) and water and doubly measure decoction 1-2 hour to 6-8, add for the second time 6-8 times of water gaging and decocted 0.5-1 hour, get medicinal liquid and useless medicinal residues;
(4) the above-mentioned medicinal liquid of combining step is condensed into clear paste behind the adding Colla Corii Asini; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1%ZTC1+1 natural clarifying agent B, fully stirs 60-80 ℃ of insulation 1-2h, add 1% ZTC1+1 natural clarifying agent A again, stir cold preservation 12-24 hour, centrifugal, get supernatant, filter, get filtrate, add adjuvant steviosin and sodium benzoate, hydro-oxidation sodium test solution adjust pH to 5-6, adding water to total amount is 1000 parts, filter, namely.
Above-mentioned steps (4) can also for: the above-mentioned medicinal liquid of combining step is condensed into clear paste; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1%ZTC1+1 natural clarifying agent B, fully stirs, and at 60-80 ℃ of insulation 1-2h, adds 1% ZTC1+1 natural clarifying agent A again, stir, cold preservation 12-24 hour, centrifugal, get supernatant, filter, get filtrate; Get Colla Corii Asini and add water-solubleization, filter, filtrate and above-mentioned filtrate merge, and add adjuvant steviosin and sodium benzoate, hydro-oxidation sodium test solution adjust pH to 5-6, and adding water to total amount is 1000 parts, filters, namely.Wherein being condensed into clear paste is: be condensed into the clear paste that every 1ml contains crude drug 1g.
Preferably: the consumption of each crude drug is: 125 parts of Rhizoma Dioscoreaes, 75 parts of Radix Dipsacis, 100 parts of the Radixs Astragali, 75 parts of Radix Angelicae Sinensis, 100 parts of Rhizoma Cibotii, 75 parts of Semen Cuscutae, 50 parts of Herba Taxillis, 75 parts of the Cortexs Eucommiae, 75 parts of Fructus Psoraleaes, 75 parts of Radix Codonopsis, 100 parts in Poria, 75 parts of the Rhizoma Atractylodis Macrocephalaes, 25 parts in Colla Corii Asini, 100 parts of Radix Rehmanniae, 75 parts of Fructus Corni, 100 parts of Fructus Lycii, 50 parts of Fructus Mumes, 75 parts of the Radix Paeoniae Albas, 50 parts of Fructus Amomis, 50 parts of Fructus Alpiniae Oxyphyllaes, 75 parts of Radix Boehmeriaes, 50 parts of Radix Scutellariaes, 8.3 parts of Folium Artemisiae Argyis.
Wherein said Rhizoma Cibotii is the unhairing Rhizoma Cibotii, and the Cortex Eucommiae is Cortex Eucommiae (parched), and the Rhizoma Atractylodis Macrocephalae is Rhizoma Atractylodis Macrocephalae preparata.
Two of technical solution of the present invention: preparation method may further comprise the steps:
(1) takes by weighing Radix Angelicae Sinensis, Semen Cuscutae, Fructus Corni, Fructus Amomi, Fructus Alpiniae Oxyphyllae, Folium Artemisiae Argyi 6 flavors by the prescription weight ratio and be ground into coarse powder, after adding the water infiltration that 6-10 doubly measures, adopt steam distillation, collect distillate and medicinal residues, distillate is 4 ℃ of-6 ℃ of cold preservations, 12-24 hour, separate oil reservoir and get water saturation volatile oil, aqueous solution device is in addition collected;
(2) except Colla Corii Asini and Radix Scutellariae, all the other 15 flavor medical materials decoct with water secondary with combining step (1) medicinal residues after 50-60 ℃ of warm water soaking 3-6 hours in the prescription, add water to 6-10 for the first time and doubly measure, and boil back adding radix scutellariae medicinal materials and fry in shallow oil altogether, decoct 1-3 hour; Add for the second time 6-10 times of water gaging and decocted 1-1.5 hour, filter, twice decocting liquid merge medicinal liquid, medicinal residues are deposited in addition;
(3) merge above-mentioned steps (1) aqueous solution and step (2) medicinal liquid, add Colla Corii Asini and be condensed into clear paste, respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1% ZTC1+1 natural clarifying agent B, fully stirs, 60 ℃-80 ℃ insulation 1-2h, add 1% ZTC1+1 natural clarifying agent A again, stir cold preservation 12-24 hours, centrifugal, get supernatant, filter, get filtrate;
(4) with step (1) gained water saturation volatile oil and step (3) gained filtrate, mix homogeneously adds adjuvant steviosin and sodium benzoate, hydro-oxidation sodium test solution adjust pH to 5-6, and adding water to total amount is 1000 parts, filter, embedding, sterilization, namely.
Above-mentioned steps (3) can also for: merge above-mentioned steps (1) aqueous solution and step (2) medicinal liquid, be condensed into clear paste; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1%ZTC1+1 natural clarifying agent B, fully stirs, and at 60-80 ℃ of insulation 1-2h, adds 1% ZTC1+1 natural clarifying agent A again, stir, cold preservation 12-24 hour, centrifugal, get supernatant, filter, get filtrate; Get Colla Corii Asini and add water-solubleization, filter, filtrate and above-mentioned filtrate merge, and get merging filtrate.Wherein being condensed into clear paste is: be condensed into the clear paste that every 1ml contains crude drug 1g.
Being condensed into clear paste behind the adding Colla Corii Asini described in the technical solution of the present invention is: be condensed into the clear paste that every 1ml contains crude drug 1g after adding Colla Corii Asini.
Wherein add adjuvant for adding adjuvant by the medicine liquid volume number: steviosin 0.2-0.5g/L and sodium benzoate 1.5-2g/L.
Pretreating agent is pharmaceutical adjunct, and pretreating agent B and ZTC1+1 natural clarifying agent B use zymolysis technique as the coupling clarifier, the substance decomposition of correspondence can be become micromolecule, further improve filter efficiency and stability of formulation, and clarifier is got assosting effect.
Pretreating agent is the compound enzyme of light yellow soluble solids powder or brown liquid, comprises amylase, pectase, protease and cellulase.Usually the ZTC1+1 pretreating agent (ZTC1+1 natural clarifying agent pretreating agent) that adopts Beijing to become the clarification technique company limited to produce in positive day.The B component that described pretreating agent B is the ZTC1+1 pretreating agent.
Described ZTC1+1 natural clarifying agent is ZTC1+1 (III) natural clarifying agent or ZTC1+1 (IV) natural clarifying agent, divides A component and B component.
Three of technical solution of the present invention: the purposes of described YUNKANG KOUFUYE in preparation treatment renal deficiency type or weak type of qi and blood threatened abortion or habitual abortion medicine.
Above-described percent is mass percent except specifying.
Beneficial effect of the present invention:
(1) elder generation of the Chinese medicine in technical solution of the present invention branch is carried closing again and is fried in shallow oil, and can effectively effective ingredient fully be extracted, and ensures drug quality to greatest extent, can preserve the Chinese prescription combination principle again, preserves the effect that all medicines share, and guarantees that medicine adapts to clinical better;
(2) in conjunction with physicochemical property and the pharmacological research of our medical material, determine its extraction process: Radix Angelicae Sinensis, Semen Cuscutae, Fructus Corni, Fructus Amomi, Fructus Alpiniae Oxyphyllae, Folium Artemisiae Argyi etc. are ground into coarse powder to technical solution of the present invention simultaneously, collect the volatile oil composition by steam distillation; All the other medical material decoctings boil;
(3) the present invention adopts ZTC1+1 (IV) natural clarifying agent to replace ethanol to remove corase particles and starch, tannin, colloid albumen isocolloid labile element and impurity in the decocting liquid, to effective ingredient such as flavone, polysaccharide, saponin, effective ingredient such as alkaloid do not have influence.This law inherited existing prescription advantage, kept full side's effective ingredient, improved quality and the stability of medicine, reduced production cost and cycle, guaranteed the curative effect of medicine;
(4) YUNKANG KOUFUYE is the big compound preparation of Chinese medicine, complicated component, and the mouthfeel bitterness selects for use steviosin as sweeting agent place of sucrose and Mel, and it has enlarged clinical adaptation population, can effectively reduce the sickness rate of gestational diabetes, for baby's health is contributed.
The specific embodiment
The present invention is by the following examples can the invention will be further described, yet scope of the present invention is not limited to following embodiment.
Embodiment 1: the consumption by each crude drug is: 125 parts of Rhizoma Dioscoreaes, 75 parts of Radix Dipsacis, 100 parts of the Radixs Astragali, 75 parts of Radix Angelicae Sinensis, 100 parts of Rhizoma Cibotii, 75 parts of Semen Cuscutae, 50 parts of Herba Taxillis, 75 parts of the Cortexs Eucommiae, 75 parts of Fructus Psoraleaes, 75 parts of Radix Codonopsis, 100 parts in Poria, 75 parts of the Rhizoma Atractylodis Macrocephalaes, 25 parts in Colla Corii Asini, 100 parts of Radix Rehmanniae, 75 parts of Fructus Corni, 100 parts of Fructus Lycii, 50 parts of Fructus Mumes, 75 parts of the Radix Paeoniae Albas, 50 parts of Fructus Amomis, 50 parts of Fructus Alpiniae Oxyphyllaes, 75 parts of Radix Boehmeriaes, 50 parts of Radix Scutellariaes, 8.3 parts of Folium Artemisiae Argyis.
(1) get recipe quantity Rhizoma Dioscoreae, the Radix Astragali, Radix Angelicae Sinensis, Fructus Psoraleae, Radix Codonopsis, Radix Scutellariae, the Radix Paeoniae Alba, Fructus Corni and Fructus Lycii with 50-60 ℃ of warm water soaking 3-6 hours, filter, filtrate for later use, filtering residue adds 6-10 times of water gaging and decocted 1-3 hour, gets medicinal liquid and medicinal residues;
(2) except Colla Corii Asini, all the other 13 flavors filtered with 50-60 ℃ of warm water soaking 3-6 hours, filtrate for later use, and filtering residue adds 6-10 times of water gaging and decocted 1-3 hour, gets medicinal liquid and medicinal residues;
(3) medicinal residues that decoct in the step (1) being remerged the medicinal residues that decoct in the step (2) adds water and fries in shallow oil secondary altogether, add for the first time filtrate in step (1) and the step (2) and water and doubly measure decoction 1-2 hour to 6-8, add for the second time 6-8 times of water gaging and decocted 0.5-1 hour, get medicinal liquid and useless medicinal residues;
(4) the above-mentioned medicinal liquid of combining step is condensed into the clear paste that every 1ml contains crude drug 1g after being blended into Colla Corii Asini; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% ZTC1+1 pretreating agent B and 1%ZTC1+1 (IV) natural clarifying agent B, fully stirs 70 ℃ of insulation 1h, add 1% ZTC1+1 (IV) natural clarifying agent A again, stir cold preservation 18 hours, centrifugal, get supernatant, filter, get filtrate, hydro-oxidation sodium test solution adjust pH to 5-6, adding water to total amount is 1000 parts, presses the medicine liquid volume number and adds adjuvant 0.5g/L steviosin and 2g/L sodium benzoate, filter, namely.
Above-mentioned steps (4) can also for: the above-mentioned medicinal liquid of combining step is condensed into the clear paste that every 1ml contains crude drug 1g; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1%ZTC1+1 natural clarifying agent B, fully stirs, and at 70 ℃ of insulation 1h, adds 1% ZTC1+1 natural clarifying agent A again, stir, and cold preservation 18 hours, centrifugal, get supernatant, filter, get filtrate; Get Colla Corii Asini and add water-solubleization, filter, filtrate and above-mentioned filtrate merge, and add adjuvant steviosin and sodium benzoate, hydro-oxidation sodium test solution adjust pH to 5-6, adding water to total amount is 1000 parts, filters, press the medicine liquid volume number and add adjuvant 0.5g/L steviosin and 2g/L sodium benzoate, filter, namely.
Embodiment 2:
Consumption by each crude drug is: 130 parts of Rhizoma Dioscoreaes, 80 parts of Radix Dipsacis, 105 parts of the Radixs Astragali, 80 parts of Radix Angelicae Sinensis, 105 parts of Rhizoma Cibotii, 80 parts of Semen Cuscutae, 55 parts of Herba Taxillis, 80 parts of the Cortexs Eucommiae, 80 parts of Fructus Psoraleaes, 80 parts of Radix Codonopsis, 100 parts in Poria, 80 parts of the Rhizoma Atractylodis Macrocephalaes, 30 parts in Colla Corii Asini, 100 parts of Radix Rehmanniae, 80 parts of Fructus Corni, 100 parts of Fructus Lycii, 55 parts of Fructus Mumes, 80 parts of the Radix Paeoniae Albas, 55 parts of Fructus Amomis, 55 parts of Fructus Alpiniae Oxyphyllaes, 80 parts of Radix Boehmeriaes, 60 parts of Radix Scutellariaes, 10 parts of Folium Artemisiae Argyis
(1) takes by weighing Radix Angelicae Sinensis, Semen Cuscutae, Fructus Corni, Fructus Amomi, Fructus Alpiniae Oxyphyllae, Folium Artemisiae Argyi 6 flavors by the prescription weight ratio and be ground into coarse powder, after adding the water infiltration of 6 times of amounts, adopt steam distillation, collect 1000 parts of distillates and medicinal residues, distillate is 4 ℃ of-6 ℃ of cold preservations, 24 hours, separate oil reservoir and get water saturation volatile oil, aqueous solution device is in addition collected;
(2) except Colla Corii Asini and Radix Scutellariae, all the other 15 flavor medical materials decoct with water secondary with 50-60 ℃ of warm water soaking combining step (1) medicinal residues after 4 hours in the prescription, add water to 8 times of amounts for the first time, boil back adding radix scutellariae medicinal materials and fry in shallow oil altogether, decoct 2 hours; Add for the second time 8 times of water gagings and decocted 1 hour, filter, twice decocting liquid merge medicinal liquid, medicinal residues are deposited in addition;
(3) merge above-mentioned steps (1) aqueous solution and step (2) medicinal liquid, be blended into Colla Corii Asini, be condensed into the clear paste that every 1ml contains crude drug 1g, respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% ZTC1+1 pretreating agent B and 1% ZTC1+1 (IV) natural clarifying agent B, fully stir, 70 ℃ of insulation 1h add 1% ZTC1+1 (IV) natural clarifying agent A again, stir, cold preservation 18 hours, centrifugal, get supernatant, filter, get filtrate;
(4) with step (1) gained water saturation volatile oil and step (3) gained filtrate, mix homogeneously, hydro-oxidation sodium test solution adjust pH to 5-6, adding water to total amount is 1000 parts, presses the medicine liquid volume number and adds adjuvant 0.5g/L steviosin and 2g/L sodium benzoate, filters, embedding, sterilization, namely.
Above-mentioned steps (3) can also for: merge above-mentioned steps (1) aqueous solution and step (2) medicinal liquid, be condensed into the clear paste that every 1ml contains crude drug 1g; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1%ZTC1+1 natural clarifying agent B, fully stirs, and at 70 ℃ of insulation 1h, adds 1% ZTC1+1 natural clarifying agent A again, stir, and cold preservation 18 hours, centrifugal, get supernatant, filter, get filtrate; Get Colla Corii Asini and add water-solubleization, filter, filtrate and above-mentioned filtrate merge, and get merging filtrate.
The pretreating agent that adopts and ZTC1+1 (IV) natural clarifying agent are removed the colloid labile element in the medicinal liquid, mainly comprise invalid components such as starch, tannin, protein and resin, this method is to effective ingredient such as flavone simultaneously, polysaccharide, effective ingredient such as alkaloid do not have adsorption, have kept the effective ingredient of the majority in this prescription.The concentration of ZTC1+1 (IV) natural clarifying agent is 1%, and addition is 0.5% of medicine liquid volume, is divided into A component and B component, and addition sequence is first B component, back A component.
Clarifier pretreating agent B: the ZTC1+1 pretreating agent that adopts Beijing to become the clarification technique company limited to produce in positive day in the present embodiment.It is an amount of to get the ZTC1+1 pretreating agent, and adding distil water stirs, and fully swelling stirs, and places, and is mixed with 0.3% ZTC1+1 pretreating agent B.
The preparation of ZTC1+1 (IV) natural clarifying agent A component: it is an amount of to get the A component, and adding distil water stirs, and fully swelling stirs, and places, and is mixed with 1% viscose liquid.
The preparation of ZTC1+1 (IV) natural clarifying agent B component: it is an amount of to get the B component, adds a spot of 0.1% acetum, stirs into pasty state, adds the acetum of the abundant swelling 0.1% of q.s again, and fully swelling stirs, and places, and is mixed with 1% viscose liquid.
Specification: 10ml/ props up; Carry out pilot plant test by above-described embodiment 1,2 technologies and each get 3 batch samples, the every index of YUNKANG KOUFUYE that the pilot plant test proof is improved the technology preparation all meets 2010, and " requirement of Chinese pharmacopoeia illustrates and improves craft science, and is rationally feasible, is suitable for big production.
The comparative efficacy test
One, purpose: observe more pregnant recovering capsule (the credible Pharmaceutical of the Ji people), former technology YUNKANG KOUFUYE and embodiment 1, the effect of the mice blood coagulation hemostasis of 2 YUNKANG KOUFUYE A, the B that prepare and the influence of antiabortive anti-abortional effect by pharmacological evaluation.
Two, method: experiment with BAOTAILING PIAN as positive control drug, more pregnant recovering capsule (Ji the people credible Pharmaceutical), former technology YUNKANG KOUFUYE and embodiment 1, the influence in the 2 mice blood coagulation bleeding times of YUNKANG KOUFUYE A, B that prepare and to the influence of the anti-abortional effect of due to diethylstilbestrol, miscarrying.
Three, material
1, laboratory animal: Kunming kind female mice, body weight 18-22g;
2, medicine: pregnant recovering capsule (the credible pharmaceutcal corporation, Ltd of the Ji people); Former technology prepares YUNKANG KOUFUYE; Embodiment 1,2 preparation YUNKANG KOUFUYE A, B; BAOTAILING PIAN market is bought.
Medicine is formed:
Rhizoma Dioscoreae 125 g, Radix Dipsaci 75 g, the Radix Astragali 100 g, Radix Angelicae Sinensis 75 g, Rhizoma Cibotii (unhairing) 100g, Semen Cuscutae 75g, Herba Taxilli 50g, the Cortex Eucommiae (stir-fry) 75g, Fructus Psoraleae 75 g, Radix Codonopsis 75g, Poria 100g, the Rhizoma Atractylodis Macrocephalae (Jiao) 75g, Colla Corii Asini 25 g, Radix Rehmanniae 100g, Fructus Corni 75g, Fructus Lycii 100g, Fructus Mume 50 g, Radix Paeoniae Alba 75g, Fructus Amomi 50g, Fructus Alpiniae Oxyphyllae 50g, Radix Boehmeriae 75 g, Radix Scutellariae 50g, Folium Artemisiae Argyi 8.3g.
(1) former technology prepares YUNKANG KOUFUYE:
More than 23 the flavor, except Colla Corii Asini, get recipe quantity Rhizoma Dioscoreae, the Radix Astragali, Radix Angelicae Sinensis, Fructus Psoraleae, Radix Codonopsis, Radix Scutellariae, the Radix Paeoniae Alba, Fructus Corni, Fructus Lycii etc. 22 flavor medical materials with 50-60 ℃ of warm water soaking 4 hours, filtration, filtrate for later use, medicinal residues decoct with water 3 times (2 hours, 1 hour, 0.5 hour), filter, merge above-mentioned medicinal liquid, be condensed into the clear paste that the every 1ml of 1:1(contains crude drug 1g behind the adding Colla Corii Asini).Adding ethanol, to make medicinal liquid contain alcohol amount be 70%, left standstill 24 hours, and drew supernatant, reclaim ethanol, filter, filtrate adds an amount of Mel, sucrose water and sodium benzoate (counting 3 ‰ with benzoic acid), hydro-oxidation sodium test solution adjust pH to 5-6, and adding water to total amount is 1200ml, filter, embedding, sterilization, namely.
(2) embodiment 1 preparation YUNKANG KOUFUYE A.
(3) embodiment 2 preparation YUNKANG KOUFUYE B.
3, main pharmacological evaluation and result thereof
(1) to the influence of clotting time of mice
The healthy female Mus of Kunming kind, body weight 18-22g, according to the randomly assigne grouping, being divided into is 6 groups, 10 every group.Matched group is irritated stomach with the normal saline of volume; Former technology prepares YUNKANG KOUFUYE 10g crude drug/k; Embodiment 1,2 preparation YUNKANG KOUFUYE A, B 10g crude drug/kg; BAOTAILING PIAN group gastric infusion 10g crude drug/kg; Pregnant recovering capsule (the credible Pharmaceutical of the Ji people) 10g crude drug/kg, successive administration 3d, each once behind last administration 1h, is plucked eyeball and gets blood sooner or later, drips on microscope slide, and choosing the blood streak with syringe needle is the blood coagulation terminal time, measures clotting time.The results are shown in Table 1
The influence of table 1 pair clotting time of mice (x ± s, n=10)
| Grouping | Animal (only) | Dosage (g/kg) | Clotting time (min) |
| Blank group | 10 | ------ | 1.36±0.2 |
| The BAOTAILING PIAN group | 10 | 10 | 1.08±0.13** |
| YUNKANG KOUFUYE A | 10 | 10 | 0.95±0.11**△ |
| YUNKANG KOUFUYE B | 10 | 10 | 0.92±0.16**△ |
| YUNKANG KOUFUYE (former technology) | 10 | 10 | 1.06±0.15**# |
| Pregnant recovering capsule (the credible Pharmaceutical of the Ji people) | 10 | 10 | 1.05±0.13**# |
With matched group * * p＜0.01; With BAOTAILING PIAN group △ P＜0.05, #P〉0.05
The result: former technology YUNKANG KOUFUYE, YUNKANG KOUFUYE A, B and the spirit of preventing miscarriage, pregnant recovering capsule all can shorten clotting time and get anastalsis, compare tool utmost point significant difference with matched group; Embodiment 1,2 preparation YUNKANG KOUFUYE A, B have significant difference than BAOTAILING PIAN, and anastalsis is the strongest.
(2) to the influence in mice bleeding time
The healthy female Mus of Kunming kind, body weight 18-22g, according to the randomly assigne grouping, being divided into is 6 groups, 10 every group.Matched group is irritated stomach with the normal saline of volume; Former technology prepares YUNKANG KOUFUYE 10g crude drug/k; Embodiment 1,2 preparation YUNKANG KOUFUYE A, B 10g crude drug/kg; BAOTAILING PIAN group gastric infusion 10g crude drug/kg; Pregnant recovering capsule (the credible Pharmaceutical of the Ji people) 10g crude drug/kg, successive administration 3d, each is once fixed mice behind last administration 1h sooner or later, is used for mice docking method and measures the bleeding time
The influence of table 2 pair clotting time of mice (x ± s, n=10)
| Grouping | Animal (only) | Dosage (g/kg) | Bleeding time (min) |
| Blank group | 10 | ------ | 9.36±0.2 |
| The BAOTAILING PIAN group | 10 | 10 | 7.88±0.13** |
| YUNKANG KOUFUYE A | 10 | 10 | 6.55±0.18**△ |
| YUNKANG KOUFUYE B | 10 | 10 | 6.52±0.13**△ |
| YUNKANG KOUFUYE (former technology) | 10 | 10 | 7.55±0.18**# |
| Pregnant recovering capsule (the credible Pharmaceutical of the Ji people) | 10 | 10 | 7.36±0.18**# |
With matched group * * p＜0.01; With BAOTAILING PIAN group △ P＜0.05, #P〉0.05
Result: YUNKANG KOUFUYE A, B and the spirit of preventing miscarriage, pregnant recovering capsule all can shorten clotting time and get anastalsis, compare tool utmost point significant difference with matched group; Embodiment 1,2 preparation YUNKANG KOUFUYE A, B have significant difference than BAOTAILING PIAN, and anastalsis is the strongest.
(3) to the influence of the anti-abortional effect of miscarrying due to the diethylstilbestrol
Kunming mouse, the female Mus 28-30g of body weight, male Mus 35-40g. mice is in female: male (2:1) ratio mates copulation.Detect the day of cloudy bolt for pregnant first day, at random 120 mices are divided into 6 groups, 20 every group.Matched group and model group are irritated the normal saline of stomach equal volume; Former technology prepares YUNKANG KOUFUYE gastric infusion 10g crude drug/kg; Embodiment 1,2 preparation YUNKANG KOUFUYE A, B gastric infusion 10g crude drug/kg; BAOTAILING PIAN group gastric infusion 10g crude drug/kg, successive administration 10d, sooner or later respectively once.Except matched group, in pregnant 7-8 day continuous subcutaneous injection diethylstilbestrol 2d, the isopyknic normal saline 2d of matched group subcutaneous injection, each organizes mice in gestation execution on the 18th, dissects, and observes each group tire number alive.The results are shown in Table 3
The anti-abortional effect of abortion model due to the table 3 pair diethylstilbestrol (x ± s, n=20)
| Grouping | Animal (only) | Dosage (g/kg) | Tire number alive | Tire rate (%) alive |
| Blank group | 20 | -- | 13.1±1.8 | 100 |
| Model group | 20 | --- | 2.5±1.4 | 26.7 |
| The BAOTAILING PIAN group | 20 | 10 | 9.6±1.7** | 76.6 |
| YUNKANG KOUFUYE A | 20 | 10 | 10.8±1.5**△ | 81.2 |
| YUNKANG KOUFUYE B | 20 | 10 | 10.6±1.7**△ | 80.8 |
| YUNKANG KOUFUYE (former technology) | 20 | 10 | 9.7±1.1**# | 74.2 |
| Pregnant recovering capsule (the credible Pharmaceutical of the Ji people) | 20 | 10 | 9.4±1.3**# | 72.3 |
With matched group * * p＜0.01; With BAOTAILING PIAN group △ P＜0.05, #P〉0.05
The result: former technology prepares YUNKANG KOUFUYE, embodiment 1,2 preparation YUNKANG KOUFUYE A, B and the spirit of preventing miscarriage, and pregnant recovering capsule all has anti-abortional effect, compares tool utmost point significant difference with matched group; Embodiment 1,2 preparation YUNKANG KOUFUYE A, B have significant difference than BAOTAILING PIAN, and anti-abortional effect is the strongest.
Research summary of the present invention:
The YUNKANG KOUFUYE patent No. 200810120726.3 is a kind of Chinese patent medicines of having sold, and this side's prescription is scientific and reasonable.Be used for renal deficiency type and weak type of qi and blood threatened abortion and habitual abortion since this medicine is produced always, obtain certain curative effect; But curative effect is not remarkable in the process of practical application, and cure rate is low.The present invention gropes by a large amount of experiments on the basis of inheriting former side, finds that because our medical material is formed complexity, having more than of drug effect of performance is single or the simple combination of several effective ingredient, but effective component group.And the former technology of YUNKANG KOUFUYE has been continued to use the method for the extraction purification of traditional " water extract-alcohol precipitation ", causes a lot of loss of active ingredients, causes this side's curative effect to reduce, and cure rate is low, the curative effect instability.Embodiment 1,2 in conjunction with the physicochemical property with reference to each medicine ingredient, fully use modern science and technology and means, carry out design and the screening of extracting method, employing ZTC1+1 (IV) natural clarifying agent replacement ethanol is removed colloid labile element and the impurity in the decocting liquid, to effective ingredient such as flavone, polysaccharide, saponin, effective ingredient such as alkaloid do not have influence, have improved quality and the stability of medicine, have guaranteed the curative effect of medicine, select for use steviosin as sweeting agent place of sucrose and Mel simultaneously, it has enlarged clinical adaptation population, can effectively reduce the sickness rate of gestational diabetes, for baby's health is contributed.YUNKANG KOUFUYE A, the B that we also will improve technology preparation and former technology prepare YUNKANG KOUFUYE, BAOTAILING PIAN, pregnant recovering capsule (the credible Pharmaceutical of the people of helping) etc. and carry out the test of pesticide effectiveness and contrast, find that improvement technology prepares YUNKANG KOUFUYE A, B and can shorten mice blood coagulation bleeding stopping period, abortion model due to the diethylstilbestrol is had anti-abortional effect, and effect all is better than the YUNKANG KOUFUYE of former technology preparation, pregnant recovering capsule (the credible Pharmaceutical of the Ji people) and BAOTAILING PIAN.
Claims (9)
1. a YUNKANG KOUFUYE for the treatment of miscarriage is characterized in that being made as follows by following each bulk drugs: 115-130 parts of Rhizoma Dioscoreaes, 70-80 parts of Radix Dipsacis, 90-110 parts of the Radixs Astragali, 70-80 parts of Radix Angelicae Sinensis, 90-110 parts of Rhizoma Cibotii, 70-80 parts of Semen Cuscutae, 40-60 parts of Herba Taxillis, 70-80 parts of the Cortexs Eucommiae, 70-80 parts of Fructus Psoraleaes, 70-80 parts of Radix Codonopsis, 90-110 parts in Poria, 70-80 parts of the Rhizoma Atractylodis Macrocephalaes, 20-30 parts in Colla Corii Asini, 90-110 parts of Radix Rehmanniae, 70-80 parts of Fructus Corni, 90-110 parts of Fructus Lycii, 40-60 parts of Fructus Mumes, 70-80 parts of the Radix Paeoniae Albas, 40-60 parts of Fructus Amomis, 40-60 parts of Fructus Alpiniae Oxyphyllaes, 70-80 parts of Radix Boehmeriaes, 40-60 parts of Radix Scutellariaes, 5-15 parts of Folium Artemisiae Argyis;
(1) get recipe quantity Rhizoma Dioscoreae, the Radix Astragali, Radix Angelicae Sinensis, Fructus Psoraleae, Radix Codonopsis, Radix Scutellariae, the Radix Paeoniae Alba, Fructus Corni and Fructus Lycii with 50-60 ℃ of warm water soaking 3-6 hours, filter, filtrate for later use, filtering residue adds 6-10 times of water gaging and decocted 1-3 hour, gets medicinal liquid and medicinal residues;
(2) except Colla Corii Asini, all the other 13 flavors filtered with 50-60 ℃ of warm water soaking 3-6 hours, filtrate for later use, and filtering residue adds 6-10 times of water gaging and decocted 1-3 hour, gets medicinal liquid and medicinal residues;
(3) medicinal residues that decoct in the step (1) being remerged the medicinal residues that decoct in the step (2) adds water and fries in shallow oil secondary altogether, add for the first time filtrate in step (1) and the step (2) and water and doubly measure decoction 1-2 hour to 6-8, add for the second time 6-8 times of water gaging and decocted 0.5-1 hour, get medicinal liquid and useless medicinal residues;
(4) medicinal liquid of merging above-mentioned steps is condensed into the clear paste that every 1ml contains crude drug 1g behind the adding Colla Corii Asini; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1%ZTC1+1 natural clarifying agent B, fully stir, 60-80 ℃ of insulation 1-2h, add 1% ZTC1+1 natural clarifying agent A again, stir, cold preservation 12-24 hour, centrifugal, get supernatant, filter, get filtrate, add adjuvant steviosin and sodium benzoate, wherein add adjuvant for adding adjuvant by the medicine liquid volume number: steviosin 0.2-0.5g/L and sodium benzoate 1.5-2g/L, hydro-oxidation sodium test solution adjust pH to 5-6, adding water to total amount is 1000 parts, filters, namely.
2. a kind of YUNKANG KOUFUYE for the treatment of miscarriage according to claim 1 is characterized in that the consumption of each crude drug is: 125 parts of Rhizoma Dioscoreaes, 75 parts of Radix Dipsacis, 100 parts of the Radixs Astragali, 75 parts of Radix Angelicae Sinensis, 100 parts of Rhizoma Cibotii, 75 parts of Semen Cuscutae, 50 parts of Herba Taxillis, 75 parts of the Cortexs Eucommiae, 75 parts of Fructus Psoraleaes, 75 parts of Radix Codonopsis, 100 parts in Poria, 75 parts of the Rhizoma Atractylodis Macrocephalaes, 25 parts in Colla Corii Asini, 100 parts of Radix Rehmanniae, 75 parts of Fructus Corni, 100 parts of Fructus Lycii, 50 parts of Fructus Mumes, 75 parts of the Radix Paeoniae Albas, 50 parts of Fructus Amomis, 50 parts of Fructus Alpiniae Oxyphyllaes, 75 parts of Radix Boehmeriaes, 50 parts of Radix Scutellariaes, 8.3 parts of Folium Artemisiae Argyis.
3. a kind of YUNKANG KOUFUYE for the treatment of miscarriage according to claim 1 and 2 is characterized in that wherein said Rhizoma Cibotii is the unhairing Rhizoma Cibotii, and the Cortex Eucommiae is Cortex Eucommiae (parched), and the Rhizoma Atractylodis Macrocephalae is Rhizoma Atractylodis Macrocephalae preparata.
4. a kind of YUNKANG KOUFUYE for the treatment of miscarriage according to claim 1, it is characterized in that described step (4) is: the above-mentioned medicinal liquid of combining step is condensed into clear paste; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1%ZTC1+1 natural clarifying agent B, fully stirs, and at 60-80 ℃ of insulation 1-2h, adds 1% ZTC1+1 natural clarifying agent A again, stir, cold preservation 12-24 hour, centrifugal, get supernatant, filter, get filtrate; Get Colla Corii Asini and add water-solubleization, filter, filtrate and above-mentioned filtrate merge, add adjuvant steviosin and sodium benzoate, wherein add adjuvant for adding adjuvant by the medicine liquid volume number: steviosin 0.2-0.5g/L and sodium benzoate 1.5-2g/L, hydro-oxidation sodium test solution adjust pH to 5-6, adding water to total amount is 1000 parts, filter, namely.
5. a YUNKANG KOUFUYE for the treatment of miscarriage is characterized in that being made as follows by following each bulk drugs: 115-130 parts of Rhizoma Dioscoreaes, 70-80 parts of Radix Dipsacis, 90-110 parts of the Radixs Astragali, 70-80 parts of Radix Angelicae Sinensis, 90-110 parts of Rhizoma Cibotii, 70-80 parts of Semen Cuscutae, 40-60 parts of Herba Taxillis, 70-80 parts of the Cortexs Eucommiae, 70-80 parts of Fructus Psoraleaes, 70-80 parts of Radix Codonopsis, 90-110 parts in Poria, 70-80 parts of the Rhizoma Atractylodis Macrocephalaes, 20-30 parts in Colla Corii Asini, 90-110 parts of Radix Rehmanniae, 70-80 parts of Fructus Corni, 90-110 parts of Fructus Lycii, 40-60 parts of Fructus Mumes, 70-80 parts of the Radix Paeoniae Albas, 40-60 parts of Fructus Amomis, 40-60 parts of Fructus Alpiniae Oxyphyllaes, 70-80 parts of Radix Boehmeriaes, 40-60 parts of Radix Scutellariaes, 5-15 parts of Folium Artemisiae Argyis;
(1) takes by weighing Radix Angelicae Sinensis, Semen Cuscutae, Fructus Corni, Fructus Amomi, Fructus Alpiniae Oxyphyllae, Folium Artemisiae Argyi 6 flavors by the prescription weight ratio and be ground into coarse powder, after adding the water infiltration that 6-10 doubly measures, adopt steam distillation, collect distillate and medicinal residues, distillate is 4 ℃ of-6 ℃ of cold preservations, 12-24 hour, separate oil reservoir and get water saturation volatile oil, aqueous solution device is in addition collected;
(2) except Colla Corii Asini and Radix Scutellariae, all the other 15 flavor medical materials decoct with water secondary with combining step (1) medicinal residues after 50-60 ℃ of warm water soaking 3-6 hours in the prescription, add water to 6-10 for the first time and doubly measure, and boil back adding radix scutellariae medicinal materials and fry in shallow oil altogether, decoct 1-3 hour; Add for the second time 6-10 times of water gaging and decocted 1-1.5 hour, filter, twice decocting liquid merge medicinal liquid, medicinal residues are deposited in addition;
(3) merge above-mentioned steps (1) aqueous solution and step (2) medicinal liquid, be condensed into the clear paste that every 1ml contains crude drug 1g after adding Colla Corii Asini, respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1% ZTC1+1 natural clarifying agent B, fully stirs, 60 ℃-80 ℃ insulation 1-2h, add 1% ZTC1+1 natural clarifying agent A again, stir cold preservation 12-24 hours, centrifugal, get supernatant, filter, get filtrate;
(4) with step (1) gained water saturation volatile oil and step (3) gained filtrate, mix homogeneously, add adjuvant steviosin and sodium benzoate, wherein add adjuvant for adding adjuvant by the medicine liquid volume number: steviosin 0.2-0.5g/L and sodium benzoate 1.5-2g/L, hydro-oxidation sodium test solution adjust pH to 5-6, adding water to total amount is 1000 parts, filter, embedding, sterilization, namely.
6. a kind of YUNKANG KOUFUYE for the treatment of miscarriage according to claim 5 is characterized in that step (3) is: merge above-mentioned steps (1) aqueous solution and step (2) medicinal liquid, be condensed into clear paste; Respectively adding concentration by 0.5% of clear paste medicine liquid volume is 0.3% pretreating agent B and 1%ZTC1+1 natural clarifying agent B, fully stirs, and at 60-80 ℃ of insulation 1-2h, adds 1% ZTC1+1 natural clarifying agent A again, stir, cold preservation 12-24 hour, centrifugal, get supernatant, filter, get filtrate; Get Colla Corii Asini and add water-solubleization, filter, filtrate and above-mentioned filtrate merge, and get merging filtrate.
7. according to claim 1,4,6 arbitrary described a kind of YUNKANG KOUFUYE for the treatment of miscarriage, it is characterized in that described pretreating agent is the ZTC1+1 pretreating agent, pretreating agent B is the B component of ZTC1+1 pretreating agent; Described ZTC1+1 natural clarifying agent is ZTC1+1 III natural clarifying agent or ZTC1+1 IV natural clarifying agent, divides A component and B component.
8. a kind of YUNKANG KOUFUYE for the treatment of miscarriage according to claim 5 is characterized in that described pretreating agent is the ZTC1+1 pretreating agent, and pretreating agent B is the B component of ZTC1+1 pretreating agent; Described ZTC1+1 natural clarifying agent is ZTC1+1 III natural clarifying agent or ZTC1+1 IV natural clarifying agent, divides A component and B component.
9. the described YUNKANG KOUFUYE of claim 1 is preparing the purposes for the treatment of in renal deficiency type or weak type of qi and blood threatened abortion or the habitual abortion medicine.
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| CN106938001A (en) * | 2017-04-07 | 2017-07-11 | 四川好医生药业集团有限公司 | Heat-clearing and detoxicating oral liquid and its preparation technology |
| CN110917311A (en) * | 2018-09-20 | 2020-03-27 | 江西济民可信药业有限公司 | A Chinese medicinal oral liquid for preventing miscarriage and regulating menstrual period and climacteric period, and its preparation method |
| CN110522875B (en) * | 2019-09-12 | 2021-04-27 | 江西金水宝制药有限公司 | Preparation method of blood-nourishing miscarriage-preventing and pregnancy-preventing oral liquid |
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| CN101066417A (en) * | 2007-03-06 | 2007-11-07 | 回音必集团浙江亚东制药有限公司 | Use of Yunkang oral liquid in preparing medicine for treating menoxenia |
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| CN101066417A (en) * | 2007-03-06 | 2007-11-07 | 回音必集团浙江亚东制药有限公司 | Use of Yunkang oral liquid in preparing medicine for treating menoxenia |
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Effective date of registration: 20170526 Address after: Friendship road 311800 Zhejiang city of Zhuji province Tao Street No. 33 Patentee after: Echo Qi group Zhejiang Qi Qi Pharmaceutical Co., Ltd. Address before: Friendship road 311800 Zhejiang city of Shaoxing province Tao Street No. 31 Patentee before: Zhejiang Yadong Pharmaceutical Co., Ltd., Huiyingbi Group |