CN105147744A - Drynaria rhizome and application of extract of drynaria rhizome for preventing or treating pulmonary heart disease - Google Patents
Drynaria rhizome and application of extract of drynaria rhizome for preventing or treating pulmonary heart disease Download PDFInfo
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- CN105147744A CN105147744A CN201510718184.XA CN201510718184A CN105147744A CN 105147744 A CN105147744 A CN 105147744A CN 201510718184 A CN201510718184 A CN 201510718184A CN 105147744 A CN105147744 A CN 105147744A
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Abstract
The invention provides drynaria rhizome and the application of extract of the drynaria rhizome for preventing or treating a pulmonary heart disease. By means of the drynaria rhizome and the extract thereof, the cardio-pulmonary function can be effectively improved, pulmonary hypertension can be relieved, and the function of pulmonary circulation can be improved, so that the load of the right ventricle is reduced, various indexes of blood streams of a patient can be effectively improved, damage to the heart is reduced, and a certain protection effect on the heart is achieved.
Description
Technical field
The present invention relates to the field of Chinese medicines, be specifically related to Rhizoma Drynariae and extract thereof for preventing or treat the purposes of pulmonary heart disease.
Background technology
Rhizoma Drynariae, another name precipice Rhizoma Zingiberis Recens, rock connect Rhizoma Zingiberis Recens, delevay drynaria, the broken benefit of meat, the broken benefit of stone, flying apsaras Mus, Niu Feilong, sudden wind, moth grass, English name Drynariafortunei, belonging to Polypodiales, Davalliaceae pteridophyta, is the rhizome of Plants of Polypodiaceae Mongolian oak Herba pteridii latiusculi or drynaria baronii Diels (Qinling Mountains Mongolian oak Herba pteridii latiusculi).
Rhizoma Drynariae extract has the kidney invigorating bone strengthening, continuous hinders pain relieving, the effect such as to invigorate blood circulation, and be used for the treatment of lumbago due to renal deficiency, Hiccough and deaf, odontoseisis, falling winks frustrates, injured bone; External treatment alopecia areata, vitiligo etc.
And the application of Rhizoma Drynariae other side rarely has report.
Summary of the invention
One object of the present invention is that the compositions providing Rhizoma Drynariae, Rhizoma Drynariae extract or comprise Rhizoma Drynariae extract is preparing the purposes prevented and/or treated in the medicine of pulmonary heart disease.
Another object of the present invention is the compositions providing Rhizoma Drynariae, Rhizoma Drynariae extract or comprise Rhizoma Drynariae extract, and it is for preventing and/or treating pulmonary heart disease.
Another object of the present invention is to provide a kind of method preventing and/or treating pulmonary heart disease, and described method comprises to be used the Rhizoma Drynariae of effective dose, Rhizoma Drynariae extract to experimenter in need or comprise the compositions of Rhizoma Drynariae extract.
Based on object of the present invention, the compositions that first aspect present invention relates to Rhizoma Drynariae, Rhizoma Drynariae extract or comprises Rhizoma Drynariae extract is preparing the purposes prevented and/or treated in the medicine of pulmonary heart disease.
In one embodiment of the invention, described pulmonary heart disease comprises acute pulmonary heart disease and chronic cardiopulmonary disease.
In one embodiment of the invention, described pulmonary heart disease is caused by following reason: pulmonary infarction, adult respiratory distress syndrome, chronic obstructive pulmonary disease, primary pulmonary hypertension, bronchial asthma, wound or postoperative lung tissue disappearance, Pierre Robin syndrome, whole latter stage pneumoconiosis, sarcoidosis, obstructive sleep apnea (treatment), interstitial lung disease, drepanocytemia, pulmonary branches trachea abnormal development (neonate) or serious kyphosis.
In one embodiment of the invention, in described Rhizoma Drynariae extract, general flavone content is 30-100%.
In a specific embodiments of the present invention, the content of described total flavones is 40-100%.
In a specific embodiments of the present invention, the content of described total flavones is 40-65%.
In a specific embodiments of the present invention, the content of described total flavones is 50-65%.
In one embodiment of the invention, in described total flavones, the content of naringin is 30-100%.
In one embodiment of the invention, in described total flavones, the content of naringin is 30-90%.
In a specific embodiments of the present invention, in described total flavones, the content of naringin is 40-90%.
In a specific embodiments of the present invention, in described total flavones, the content of naringin is 50-80%.
In a preferred embodiment of the invention, in described total flavones, the content of naringin is 60-70%.
In one embodiment of the invention, in described Rhizoma Drynariae extract, the content of naringin is 20-100%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-45%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-40%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-38%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 30-40%.
In one embodiment of the invention, wherein said Rhizoma Drynariae extract prepares by the following method:
1) by Rhizoma Drynariae pulverizing medicinal materials, with water or alcohol or its mixture extracting;
2) extracting solution resin absorption;
3) having adsorbed the resin water of extract or alcohol or its mixture eluting.
In a specific embodiments of the present invention, wherein step 1) in carry out extracting with water.
In a specific embodiments of the present invention, wherein step 1) middle alcohol/aqueous mixtures carries out extracting.
In a specific embodiments of the present invention, in described alcohol/aqueous mixtures, alcohol content is 40-90% weight.
In a specific embodiments of the present invention, described alcohol is selected from methanol and ethanol.
In a specific embodiments of the present invention, wherein step 2) in resin be macroporous adsorbent resin.
In a specific embodiments of the present invention, wherein step 3) in first wash with water, then use alcohol/aqueous mixtures eluting.
In a preferred embodiment of the invention, described Rhizoma Drynariae extract prepares through following method: take Rhizoma Drynariae, is ground into coarse powder, with water (such as, the consumption of water is that every hectogram Rhizoma Drynariae crude drug adds 1.5 ~ 2L water) boil (such as, 0.5 ~ 3 hour, preferably 1 hour), release medicinal liquid, residue adds water boil (such as again, first time and second time add water ratio for (1 ~ 3): 1, such as 1.5:1), release medicinal liquid.Twice medicinal liquid merges, filter, medicinal liquid flows through and treated WLD adsorbent resin is housed (such as, the addition of resin is 1.2 ~ 1.5 times of Rhizoma Drynariae crude drug) adsorption column, effluent tetrahydro boron potassium reaction and judgement collects terminal, till namely occurring that suddenly flavanone compounds reaction-resin reaches saturated adsorption with effluent.Adsorb complete, wash resin column with water (such as, the consumption of water is that every hectogram Rhizoma Drynariae crude drug 0.2 ~ 1L washes), washing liquid discards, use ethanol again (such as, 70% ethanol) eluting (such as, the consumption of ethanol is every hectogram Rhizoma Drynariae crude drug 0.2 ~ 1L ethanol elution), judge with tetrahydro boron potassium chromogenic reaction to receive the starting point and the terminal that connect eluent.Reclaim eluent, eluent reclaims ethanol, and debris is steamed to thick paste in water-bath, vacuum drying, obtains described Rhizoma Drynariae extract.
In a preferred embodiment of the invention, the described compositions comprising Rhizoma Drynariae extract is through that following method prepares: get the Rhizoma Drynariae extract that any one of first aspect present invention is obtained, add starch, mixing, be filled with capsule, described in obtaining, comprise the compositions (every containing effective ingredient 180mg) of Rhizoma Drynariae extract.
A second aspect of the present invention relates to Rhizoma Drynariae, Rhizoma Drynariae extract or comprises the compositions of Rhizoma Drynariae extract, and it is for preventing and/or treating pulmonary heart disease.
In one embodiment of the invention, described pulmonary heart disease comprises acute pulmonary heart disease and chronic cardiopulmonary disease.
In one embodiment of the invention, described pulmonary heart disease is caused by following reason: pulmonary infarction, adult respiratory distress syndrome, chronic obstructive pulmonary disease, primary pulmonary hypertension, bronchial asthma, wound or postoperative lung tissue disappearance, Pierre Robin syndrome, whole latter stage pneumoconiosis, sarcoidosis, obstructive sleep apnea (treatment), interstitial lung disease, drepanocytemia, pulmonary branches trachea abnormal development (neonate) or serious kyphosis.
In one embodiment of the invention, in described Rhizoma Drynariae extract, general flavone content is 30-100%.
In a specific embodiments of the present invention, the content of described total flavones is below 40-100%.
In a specific embodiments of the present invention, the content of described total flavones is 40-65%.
In a specific embodiments of the present invention, the content of described total flavones is 50-65%.
In one embodiment of the invention, in described total flavones, the content of naringin is 30-100%.
In one embodiment of the invention, in described total flavones, the content of naringin is 30-90%.
In a specific embodiments of the present invention, in described total flavones, the content of naringin is 40-90%.
In a specific embodiments of the present invention, in described total flavones, the content of naringin is 50-80%.
In a preferred embodiment of the invention, in described total flavones, the content of naringin is 60-70%.
In one embodiment of the invention, in described Rhizoma Drynariae extract, the content of naringin is 20-100%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-45%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-40%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-38%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 30-40%.
In one embodiment of the invention, wherein said Rhizoma Drynariae extract prepares by the following method:
1) by Rhizoma Drynariae pulverizing medicinal materials, with water or alcohol or its mixture extracting;
2) extracting solution resin absorption;
3) having adsorbed the resin water of extract or alcohol or its mixture eluting.
In a specific embodiments of the present invention, wherein step 1) in carry out extracting with water.
In a specific embodiments of the present invention, wherein step 1) middle alcohol/aqueous mixtures carries out extracting.
In a specific embodiments of the present invention, in described alcohol/aqueous mixtures, alcohol content is 40-90% weight.
In a specific embodiments of the present invention, described alcohol is selected from methanol and ethanol.
In a specific embodiments of the present invention, wherein step 2) in resin be macroporous adsorbent resin.
In a specific embodiments of the present invention, wherein step 3) in first wash with water, then use alcohol/aqueous mixtures eluting.
In a preferred embodiment of the invention, described Rhizoma Drynariae extract prepares through following method: take Rhizoma Drynariae, is ground into coarse powder, with water (such as, the consumption of water is that every hectogram Rhizoma Drynariae crude drug adds 1.5 ~ 2L water) boil (such as, 0.5 ~ 3 hour, preferably 1 hour), release medicinal liquid, residue adds water boil (such as again, first time and second time add water ratio for (1 ~ 3): 1, such as 1.5:1), release medicinal liquid.Twice medicinal liquid merges, filter, medicinal liquid flows through and treated WLD adsorbent resin is housed (such as, the addition of resin is 1.2 ~ 1.5 times of Rhizoma Drynariae crude drug) adsorption column, effluent tetrahydro boron potassium reaction and judgement collects terminal, till namely occurring that suddenly flavanone compounds reaction-resin reaches saturated adsorption with effluent.Adsorb complete, wash resin column with water (such as, the consumption of water is that every hectogram Rhizoma Drynariae crude drug 0.2 ~ 1L washes), washing liquid discards, use ethanol again (such as, 70% ethanol) eluting (such as, the consumption of ethanol is every hectogram Rhizoma Drynariae crude drug 0.2 ~ 1L ethanol elution), judge with tetrahydro boron potassium chromogenic reaction to receive the starting point and the terminal that connect eluent.Reclaim eluent, eluent reclaims ethanol, and debris is steamed to thick paste in water-bath, vacuum drying, obtains described Rhizoma Drynariae extract.
In a preferred embodiment of the invention, the described compositions comprising Rhizoma Drynariae extract is through that following method prepares: get the Rhizoma Drynariae extract that any one of first aspect present invention is obtained, add starch, mixing, be filled with capsule, described in obtaining, comprise the compositions (every containing effective ingredient 180mg) of Rhizoma Drynariae extract.
A third aspect of the present invention relates to a kind of method preventing and/or treating pulmonary heart disease, and described method comprises uses the Rhizoma Drynariae of effective dose, Rhizoma Drynariae extract to experimenter in need or the compositions that comprises Rhizoma Drynariae extract exists.
In one embodiment of the invention, described pulmonary heart disease comprises acute pulmonary heart disease and chronic cardiopulmonary disease.
In one embodiment of the invention, described pulmonary heart disease is caused by following reason: pulmonary infarction, adult respiratory distress syndrome, chronic obstructive pulmonary disease, primary pulmonary hypertension, bronchial asthma, wound or postoperative lung tissue disappearance, Pierre Robin syndrome, whole latter stage pneumoconiosis, sarcoidosis, obstructive sleep apnea (treatment), interstitial lung disease, drepanocytemia, pulmonary branches trachea abnormal development (neonate) or serious kyphosis.
In one embodiment of the invention, described method is carried out in vitro.
In one embodiment of the invention, described method is carried out in vivo.
In one embodiment of the invention, described experimenter is mammal, such as bovid, equine species, caprid, porcine animals, Canis animals, felid, rodent, primate; Wherein, particularly preferably experimenter behaves.
In one embodiment of the invention, in described Rhizoma Drynariae extract, general flavone content is 30-100%.
In a specific embodiments of the present invention, the content of described total flavones is 40-100%.
In a specific embodiments of the present invention, the content of described total flavones is 40-65%.
In a specific embodiments of the present invention, the content of described total flavones is 50-65%.
In one embodiment of the invention, in described total flavones, the content of naringin is 30-100%.
In one embodiment of the invention, in described total flavones, the content of naringin is 30-90%.
In a specific embodiments of the present invention, in described total flavones, the content of naringin is 40-90%.
In a specific embodiments of the present invention, in described total flavones, the content of naringin is 50-80%.
In a preferred embodiment of the invention, in described total flavones, the content of naringin is 60-70%.
In one embodiment of the invention, in described Rhizoma Drynariae extract, the content of naringin is 20-100%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-45%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-40%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 20-38%.
In a specific embodiments of the present invention, in described Rhizoma Drynariae extract, the content of naringin is 30-40%.
In one embodiment of the invention, wherein said Rhizoma Drynariae extract prepares by the following method:
1) by Rhizoma Drynariae pulverizing medicinal materials, with water or alcohol or its mixture extracting;
2) extracting solution resin absorption;
3) having adsorbed the resin water of extract or alcohol or its mixture eluting.
In a specific embodiments of the present invention, wherein step 1) in carry out extracting with water.
In a specific embodiments of the present invention, wherein step 1) middle alcohol/aqueous mixtures carries out extracting.
In a specific embodiments of the present invention, in described alcohol/aqueous mixtures, alcohol content is 40-90% weight.
In a specific embodiments of the present invention, described alcohol is selected from methanol and ethanol.
In a specific embodiments of the present invention, wherein step 2) in resin be macroporous adsorbent resin.
In a specific embodiments of the present invention, wherein step 3) in first wash with water, then use alcohol/aqueous mixtures eluting.
In a preferred embodiment of the invention, described Rhizoma Drynariae extract prepares through following method: take Rhizoma Drynariae, is ground into coarse powder, with water (such as, the consumption of water is that every hectogram Rhizoma Drynariae crude drug adds 1.5 ~ 2L water) boil (such as, 0.5 ~ 3 hour, preferably 1 hour), release medicinal liquid, residue adds water boil (such as again, first time and second time add water ratio for (1 ~ 3): 1, such as 1.5:1), release medicinal liquid.Twice medicinal liquid merges, filter, medicinal liquid flows through and treated WLD adsorbent resin is housed (such as, the addition of resin is 1.2 ~ 1.5 times of Rhizoma Drynariae crude drug) adsorption column, effluent tetrahydro boron potassium reaction and judgement collects terminal, till namely occurring that suddenly flavanone compounds reaction-resin reaches saturated adsorption with effluent.Adsorb complete, wash resin column with water (such as, the consumption of water is that every hectogram Rhizoma Drynariae crude drug 0.2 ~ 1L washes), washing liquid discards, use ethanol again (such as, 70% ethanol) eluting (such as, the consumption of ethanol is every hectogram Rhizoma Drynariae crude drug 0.2 ~ 1L ethanol elution), judge with tetrahydro boron potassium chromogenic reaction to receive the starting point and the terminal that connect eluent.Reclaim eluent, eluent reclaims ethanol, and debris is steamed to thick paste in water-bath, vacuum drying, obtains described Rhizoma Drynariae extract.
In a preferred embodiment of the invention, the described compositions comprising Rhizoma Drynariae extract is through that following method prepares: get the Rhizoma Drynariae extract that any one of first aspect present invention is obtained, add starch, mixing, be filled with capsule, described in obtaining, comprise the compositions (every containing effective ingredient 180mg) of Rhizoma Drynariae extract.
The various term that the present invention uses and phrase have and well known to a person skilled in the art general sense, nonetheless, the present invention still wishes again to these terms and the more detailed description and interpretation of phrase, the term mentioned and phrase, if any inconsistent with common art-recognized meanings, are as the criterion with the implication that the present invention states.
Term used herein " pulmonary heart disease " full name " pulmonary heart disease ", cause lung tissue structure and (or) dysfunction by the chronic disease of lung tissue, Pulmonary Vascular or thorax, generation pulmonary vascular resistance increases, pulmonary artery pressure increases, right ventricle is expanded or (with) plump, companion or do not accompany the heart disease of right heart function exhaustion.Pulmonary heart disease early symptom is not obvious, but along with the progress of the course of disease, can there is following symptom in patient: out of breath, asthma, chronic cough, ascites, ankle and the expansion of foot's edema, neck and facial vein or outstanding, jugular vein pressure (JVP) risings, lung enlargement, cyanosis, hear sounds exception etc.
Term used herein " effective dose " refers to the amount being enough to prevent and/or treat effect needed for realization, such as, realizes prevention or alleviates the amount with the symptom of disease association to be treated.
Term used herein " treatment " refers to therapeutic treatment and preventive measure, its objective is prevention or delay (alleviating) for morbid state or disease.If after experimenter receives the described Rhizoma Drynariae of therapeutic dose, Rhizoma Drynariae extract according to methods described herein or comprises the compositions of Rhizoma Drynariae extract, one or more pulmonary heart disease indications of this experimenter and Symptoms go out observable and/or detectable reduction or improvement, then the pulmonary heart disease of experimenter is by successfully " treatment ", described pulmonary heart disease indication and symptom such as pulmonary edema, pulmonary hypertension etc.What it is also understood that the prevention of described morbid state or disease or treatment not only comprises fully prevention or treatment, also comprises and does not reach fully prevention or treatment, but achieves some biologys or the relevant result of medical science.Treatment heart failure used herein also refers to treatment any one or the multiple morbid state that may cause heart failure, includes but not limited to improve right atrium (and/or right ventricle) hemodynamics, reduce Lung Exponent, Lung water content etc.
Term used herein " prevention " refers in statistics sample, relative to untreated control sample, compositions of the present invention can reduce the generation of disease or morbid state in the sample of process, or delay disease or morbid state one or more symptoms outbreak or reduce its order of severity.Prevention pulmonary heart disease described herein comprises prevention or delay pulmonary heart disease starts, stops, postpones or slows down development or the progress of pulmonary heart disease and makes the progress of pulmonary heart disease be improved to the more early stage stage from late stage.
Rhizoma Drynariae of the present invention, Rhizoma Drynariae extract and comprise the compositions of Rhizoma Drynariae extract
Rhizoma Drynariae of the present invention (RhizomaDrynariae) refers to Polypodiaceae (PolypodiaceaeS.F.Gary) Mongolian oak Cyclosorus (Drynaria (Bory) J.Sm.) plant such as Mongolian oak Herba pteridii latiusculi Drynariafortunei (Kunze) J.Sm., Qinling Mountains Mongolian oak Herba pteridii latiusculi D.baronii (Chist) Diels, drynaria baronii Diels D.sinicaDiels, Drynaria delavayi christ D.delavayiChirst, and the rhizome of one or more plants such as Davalliaceae Davallia (DavalliaSm.) plant Rhizoma Drynariae DavalliamariesiiMooreexBak or herb.The above-mentioned plant used as Rhizoma Drynariae can be used alone or as a mixture in the present invention, and the present invention is without restriction to this.
The preparation method of Rhizoma Drynariae extract of the present invention can with reference to CN1484529A embodiment 1 method, and Rhizoma Drynariae extract exemplary manufacturing process comprises following steps:
(pulverizing medicinal materials →) water/alcohol decoction → resin absorption → (washing →) alcohol/water elution → post processing.
In said method, the pulverizing of medical material is conventional steps well-known to those skilled in the art.For the method pulverized, the present invention is without restriction.Powder after pulverizing, if granularity is excessively thick, then effective ingredient is difficult to abundant proposition; If powder is meticulous, then bring to the step of the extraction fluid after decocting unfavorable, to this, those skilled in the art can be selected according to practical experience, also do not limit this.
In order to extract effective ingredient, water and/or alcohol can be adopted to infiltrate the mode extracted, but be not easy completely, so adopt the mode heating extracting due to the leaching of effective ingredient.Heating-up temperature is the boiling point of room temperature-extraction solvent.
During heating extraction, preferably carry out (backflow) at the boiling point of solvent.
During as used merely water, at 100 DEG C, extraction time is 0.5-3 hour, extraction time 2-4 time, extract at every turn the amount of solution added make a living dose 5-20 doubly.If by alcohol or alcohol-water solution reflux, extract, then consumption make a living dose 5-20 doubly, extraction time is 0.5-3 hour, extracts 2-4 time.Alcohol can use methanol and ethanol, from the angle etc. of safety, and preferred alcohol.When adopting ethanol, the preferred 20%-90% of concentration of ethanol.For reference only, in reality as required, those skilled in the art can rule of thumb suitably change above-mentioned quantity, are understood that, this change is no more than scope of the present invention.
After obtaining extracting solution, can be filtered extracting solution as required, then extracting solution resin absorption.The resin that can be used for adsorbing is macroporous adsorbent resin, such as D101 resin (resin processing plant of Tianjin Nankai university product), AB-8 resin (Tianjin osseocolla factory product), WLD resin (Traditional Chinese Medicine Research Institute, Sichuan Province product), CAD-40 (North China Pharmaceutical Factory's product) etc., but the inventive method is not by the restriction of above-mentioned resin column model, as long as macroporous adsorbent resin, namely the inventive method can be completed.For the method for resin absorption see CN1072089A, the document is described in detail resin sorption processes, and the application refer to method disclosed in document, and as the part of the inventive method, is documented in present specification.
According to the result of study of the present inventor, maximum with WLD adsorption capacity in three kinds of tree resins, eluting is also easier.Therefore this extracting method preferred WLD type adsorbent resin is adsorbent.The ratio of adsorbent resin and crude drug, suitably can select between 0.5 ~ 2: 1 (weight), and preferably 0.5 ~ 1.5: 1, most preferably about 1: 1, those skilled in the art can rule of thumb suitably select.If ratio is less than 0.5: 1, then may adsorb not exclusively, if be greater than 1.5: 1, then because the flavone amount of absorption no longer increases, can resin be wasted, be unfavorable for cost.
When use adsorbent resin, according to the general knowledge that those skilled in the art are familiar with, resin should first carry out pretreatment and then could use, and pretreatment can adopt known method to carry out, such as, can operate as follows:
Resin is filled post, ethanol, concentrated hydrochloric acid (1: 1) is first used to rinse, when being washed till the water gaging dilutions such as effluent, after not aobvious muddiness, use 10 times of hot water to resin column volume (80 DEG C) instead to rinse, then rinse with 2% sodium hydroxide solution of same volume, when final rinse water to resin column effluent is neutral, with water recoil, resin is loosened, then by medicinal liquid upper prop again.
Must control the flow velocity of extracting solution during absorption, guarantee absorption completely.In general, during commercial production, use
adsorption column, in-built 100kg resin, adsorbs with 10 ~ 20L/ minute flow velocity, can ensure absorption completely.With this understanding, if higher than 20L/ minute, be then difficult to ensure that absorption completely, may reduce productive rate.If lower than 10L/ minute, then absorption expends time in, and is unfavorable for enhancing productivity.
The alcohol that after upper prop, eluting is used can be ethanol or methanol, preferred alcohol viewed from health perspectives, when adopting ethanol elution, the preferred 50-95% of concentration, from the angle that ethanol can be recycled, best 70% (become because of physical condition, also can ± 5%) left and right.
During eluting, when the consumption of alcohol and the usage ratio of medical material are 2 times amount ~ 10 times amount, when consumption is less than 2 times, eluting is incomplete.Consumption is more than 10 times, and elution amount no longer increases, nonsensical.From production angle, preferably 2 ~ 5 times amount.
After alcohol eluting, collect eluent, reconcentration after ethanol in recovery eluent, finally, pulverize after spray-dried or lyophilization or convection drying, obtain powder that is brown or rufous, gained powder can be refined further, or directly make suitable dosage form, and such as, capsule, pill, tablet, granule, solution or injection etc.
First debris should be concentrated into relative density before spraying dry is 1.10-1.18, then spraying dry.First debris should be concentrated into relative density during vacuum drying is 1.3-1.4, then vacuum drying, for processing conveniently further after dry, can be ground into fine powder.Spraying dry and vacuum drying are conventional dry technologies, and implement this step not difficult, the present invention is without restriction to this.
Extract of the present invention described above, can preparation process conveniently, is prepared into any pharmaceutical dosage form being applicable to Clinical practice, such as, and capsule, pill, tablet, granule, solution or injection etc.Wherein extract contained by each dosage form amount according to dosage form composition, treat the situation, Clinical practice condition etc. of patient and different.Generally, when general flavone content in extract is with 50% timing, patient's administration every day 0.1 ~ 5 gram, divides and takes for 1 ~ 4 time.
The compositions comprising Rhizoma Drynariae extract of the present invention refers to the Rhizoma Drynariae extract and one or more pharmaceutically acceptable carrier or excipient that comprise and prepared by said method.
The preparation of compositions of the present invention meets the route of administration of its expection.Compositions of the present invention can by following administration: parenteral, locally, intravenous, oral, subcutaneous, intra-arterial, intradermal, percutaneous, rectum, intracranial, intraperitoneal, intranasal, intramuscular route or as inhalant.Described compositions can optionally with treating in various disease other agents administration having certain effect at least.
Oral formulations comprises the acceptable inert diluent of pharmacy or edible carrier usually.Can oral formulations be encapsulated in gelatine capsule or be compressed into tablet.In order to oral therapeutic administration, the present composition can merge with excipient, and for the form of tablet, lozenge or capsule.Fluid carrier for collutory can also be used to prepare Orally administered composition, and wherein in fluid carrier, compound is oral administration, gargles and spue or swallow.Tablet, pill, capsule, lozenge etc. can contain any following compositions or have the compound of similar quality: binding agent, such as microcrystalline Cellulose, Tragacanth or gelatin; Excipient, such as starch or lactose; Disintegrate compound, such as alginic acid, Primogel or corn starch; Lubricant, such as magnesium stearate or Sterotes; Fluidizer, such as colloidal silica; Edulcorant compound, such as sucrose or glucide; Or flavor compound, such as Oleum menthae, methyl salicylate or flavoring orange essence.
In embodiments of the invention, carry out suitable external or in vivoassay whether to be applicable to treat individual institute to the effect and administration of determining the present composition and to suffer from the disease or medical condition.These examples measured are described in conjunction with disease specific or therapeutic treatment in hereafter non-limiting example.Usually, the effective dose of the present composition realizing prevention or therapeutic effect is enough to for about 0.001mg/ kg body weight/sky to about 10,000mg/ kg body weight/sky.When suitable, dosage is about 0.01mg/ kg body weight/sky to about 1000mg/ kg body weight/sky.Dosage range can be every day, every two days or every three days about 0.01 to 1000mg/kg host body weight, be more typically 0.1 to 500mg/kg host body weight.Exemplary therapeutic scheme be every two days once or once in a week or monthly administration.Usually repeatedly give described reagent, the interval between single dose can be every day, weekly, monthly or every year.Or, described reagent can be given with the form of slow releasing preparation, in this case, need less administration frequency.Dosage and frequency are different from the half-life of reagent in experimenter.Also can according to being preventative process or therapeutic treatment and different.In prophylactic use, give relatively low dosage for a long time with the interval of rather low-frequency rate.In therapeutic application, sometimes need to give relatively high dosage with relatively short interval, until the progress of disease is delayed or stops, and preferably until individuality shows the partially or completely improvement of disease symptoms, after this, patient's prevention scheme can be given.
The beneficial effect of the invention
The compositions that the invention provides Rhizoma Drynariae, Rhizoma Drynariae extract and comprise Rhizoma Drynariae extract is for the preparation of preventing and/or treating pulmonary heart disease purposes.The present invention finds that said medicine effectively can improve cardio-pulmonary function, alleviates pulmonary hypertension, improves the function of pulmonary circulation; make the load reduction of right ventricle; and effectively can improve the blood stream indices of patient, alleviate the damage to heart, have certain protective effect to heart.
Detailed description of the invention
Below in conjunction with embodiment, embodiment of the present invention are described in detail, but it will be understood to those of skill in the art that the following example only for illustration of the present invention, and should not be considered as limiting scope of the present invention.Unreceipted actual conditions person in embodiment, the condition of conveniently conditioned disjunction manufacturer suggestion is carried out.Agents useful for same or the unreceipted production firm person of instrument, being can by the conventional products of commercial acquisition.
Embodiment 1
Take 100 grams of Rhizoma Drynariae, be ground into coarse powder, boil 1 hour with water 1500ml, release medicinal liquid, residue adds 1000ml water boil again, releases medicinal liquid.Twice medicinal liquid merges, and filter, medicinal liquid flows through the adsorption column that 120 grams of treated WLD adsorbent resiies are housed
flow velocity 4ml/ divides, and effluent tetrahydro boron potassium reaction and judgement collects terminal, till namely occurring that suddenly flavanone compounds reaction-resin reaches saturated adsorption with effluent.Adsorb complete, with 500ml water washing resin post, washing liquid discards, then uses 400ml70% ethanol elution, judges to receive the starting point and the terminal that connect eluent with tetrahydro boron potassium chromogenic reaction.Reclaim eluent, eluent reclaims ethanol, and debris is steamed to thick paste in water-bath, vacuum drying, obtains Rhizoma Drynariae extract 1.88 grams.Its general flavone content surveyed by gained sample ultraviolet spectrophotometry, and general flavone content 55.08%, HPLC method measures naringin content 36.6% (accounting for 66.4% of total flavones).
Embodiment 2
Except reflux solvent and eluting solvent all adopt 70% alcoholic solution, according to the operation of embodiment 1 method, obtain extract 1.69 grams, general flavone content 53.12%, HPLC method measures naringin content 32.5% (accounting for 61.2% of total flavones).
Embodiment 3
Except adsorbent resin adopts AB-8 resin, adopt the operation of embodiment 1 same procedure, obtain 0.95 gram of extract, general flavone content 61.80%.
Embodiment 4
Except adsorbent resin adopts D101 resin, adopt the operation of embodiment 1 same procedure, obtain 1.07 grams of extracts, general flavone content 57.35%.
Embodiment 5
Except Rhizoma Drynariae amount of powder is 10 grams, adsorbent resin amount is respectively beyond 5 grams, 10 grams, 20 grams, 25 grams, according to embodiment 1 method obtain respectively extract 0.16 gram, 0.20 gram, 0.27 gram, 0.27 gram, general flavone content is respectively 53.88%, 52.29%, 42.65%, 41.88%, total flavones receipts amount is respectively 86.2mg, 104.6mg, 115.2mg, 113.1mg, and total flavones yield is respectively 0.86%, 1.05%, 1.15%, 1.13%.Visible when medical material amount: adsorbent resin amount, more than after 1: 2, almost no longer increases for its absorption total flavones amount of equivalent medical material, when illustrating that adsorbent resin amount is 2 times of medical material amount, adsorbs complete.But when medical material amount: when adsorbent resin amount is 1: 1, its adsorbate general flavone content is higher, and total flavones must be measured and reached 90.8% of complete adsorbance, and in product, general flavone content reaches 52.29%, therefore consider aborning, medical material amount: more suitable when adsorbent resin amount is 1: 1.
Embodiment 6
With the glass column (Φ=20) of 4 processed good WLD macroporous adsorbent resin 10g of filling, by Rhizoma Drynariae medicinal material coarse powder 40g, add 1000mL soak by water one hour (micro-boil), filter.Filtrate is divided into 4 parts, and every part is respectively passed through an above-mentioned glass column, and coutroi velocity is respectively 2mL/min, 4mL/min, 8mL/min and 16mL/min, and checks that result is as table 1 with or without flavonoid glycoside in waste liquid with tetrahydro boron potassium reaction.
Table 1
Find out from upper table, adsorption flow rate must control, and guarantee absorption completely.
Embodiment 7
Get Rhizoma Drynariae medicinal material coarse powder 300g, filtrate is obtained by embodiment 1 method, filtrate is divided into three parts, upper prop (Φ=40 respectively, in-built WLD resin 100g), use different concentration ethanol eluting respectively, the eluent of collection is through concentrated, dry, by its total flavones amount of determined by ultraviolet spectrophotometry, the results are shown in Table 2.
Table 2
From upper table data, concentration of alcohol has impact to elute effect, and wherein 70% ethanol elution effect is better.
Formulation example 1 capsule
Get the extract powder of the present invention that 180g obtains according to embodiment 1 method, add starch 70g, mixing, is filled with capsule, obtains the capsule (every containing effective ingredient 180mg) of 1000 extracts of the present invention.
Formulation example 2 tablet
Get 180g according to the obtained extract powder of the present invention of embodiment 1 method, mix with 70g starch, the aqueous solution then adding a small amount of sodium carboxymethyl cellulose is kneaded soft material processed, conventionally granulates, dry, and add a small amount of magnesium stearate, mixing, beats sheet.Obtain the tablet (every sheet is containing effective ingredient 180mg) of 1000 extracts of the present invention.
Formulation example 3 injection
Get of the present invention extract of 180g according to embodiment 1 method gained, add 800ml distilled water for injection, heating makes entirely molten, with filtering with microporous membrane, filtrate is put in refrigerator (4 DEG C ~ 8 DEG C) and is placed 24 hours, again use filtering with microporous membrane, regulate pH (being 6.5) and osmotic pressure to isotonic with medical hydrochloric acid (12N) and NaOH aqueous solution (12N), inject with distilled water to 1000ml, heat sterilization, filter, be sub-packed in ampoule, often prop up 5ml (containing effective ingredient 180mg).
experimental example 1 is on the hemodynamic impact of experimental lung cardiopathia
1. material
1.1 animal
Japan large ear rabbit, body weight 2.0-3.5kg, male and female dual-purpose, purchased from Norman Bethune Medical University's Experimental Animal Center.
1.2 reagent
Except as otherwise noted, this is tested medicine used and has following dosage and content:
Extract of the present invention: formulation example 1 capsule, every containing effective ingredient 0.18g;
Ferric chloride (analytical pure), Yao Hua chemical plant, Tianjin product, lot number: 090102;
Pentobarbital sodium, Beijing chemical reagents corporation (German import subpackage), lot number: 100919;
Heparin (125 μ g/mL), Chinese emerging chemical reagent institute (Shanghai), lot number: 121108.
1.3 instrument
ML880 type 16 road physiograph (Australian ADinstrurnents company).
2 methods
After 40 Japan large ear rabbit adaptabilities are fed 3 days, be divided at random 4 groups (female, heros half and half), i.e. Normal group, pulmonary heart disease model group, high dose group, low dose group, each group 10, respectively organizes the nursing of equal concentrated feed, freely drinks water.
The foundation of pulmonary heart disease model
Except blank group, the liquor ferri trichloridi of all the other each administration groups all auricular vein injections 0.5% simultaneously, the next day, injects, 1.0ml/ time, amounts to 21 days.
Beginning administration in modeling the 2nd day, high dose group (70mg/kg), low dose group (35mg/kg), by group and dosage gavage (ig) administration respectively, every day 1 time, continuous 20 days.After last administration, pentobarbital sodium is anaesthetized, and executes left side the 4th intercostal thoracotomy, connects 16 road physiographs, monitor rabbit right atrium, right ventricle and Pulmonic systolic pressure, diastolic pressure, the numerical value of 1h after record administration.
T inspection between statistical analysis employing group, with P < 0.05 for difference has statistical significance.
3 results
Table 3 is on the impact (x ± s) of pulmonary heart disease rabbit right atrial systole pressure, diastolic pressure, mean pressure
Note: compare * * P < 0.01 with normal group; △ P < 0.05, △ △ P < 0.01 is compared with model group
Table 4 is on the impact (x ± s) of pulmonary heart disease rabbit right ventricular systolic pressure, diastolic pressure, mean pressure
Note: compare * * P < 0.01 with normal group; △ P < 0.05, △ △ P < 0.01 is compared with model group
Table 5 is on the impact (x ± s) of pulmonary heart disease Rabbit Lung systolic arterial pressure, diastolic pressure, mean pressure
Note: compare * * P < 0.01 with normal group; △ P < 0.05, △ △ P < 0.01 is compared with model group
Table 3, table 4, table 5 result shows, systolic pressure, the mean pressure compared with normal matched group of model group animal right ventricle, right atrium, pulmonary artery pressure obviously raise, there is significant difference (P<0.01), diastolic pressure compared with normal matched group raises (P<0.05), hemodynamic change when meeting pulmonary heart disease right heart failure.And administration group high dose group right ventricle, right atrium systolic pressure, diastolic pressure, mean pressure, low dose group systolic pressure, mean pressure all obviously reduce, compare with model group (P<0.01, P<0.05), reduction trend is all had to pulmonary arterial systolic pressure, diastolic pressure, mean pressure, compare with model group (P>0.05), illustrate that this product can improve the cardio-pulmonary function of Rabbit Lung cardiopathia model extremely.
experimental example 2 is on the impact of rat acute pulmonary heart disease
1. material
1.1 animal
Cleaning grade male Wistar rat 60, body weight (200 ± 20) g, is provided by Jilin University's Experimental Animal Center, quality certification SCXK (Ji) 2012-0001, and ad lib is drunk water.
1.2 reagent
Except as otherwise noted, this is tested medicine used and has following dosage and content:
Extract of the present invention: formulation example 1 capsule, every containing effective ingredient 0.18g.
Epinephrine inj, BJ Pharmaceutical Co., Ltd., lot number: 091115;
Pentobarbital sodium, Beijing chemical reagents corporation (German import subpackage), lot number: 100919.
1.3 instrument
AR1140 type electronic balance (precision: 0.0001), Ohaus Instrument (Shanghai) Co., Ltd.;
The rotary paraffin slicing machine of LelcaRM2135 (Leica Germany);
Olympus microscope (Japan).
2. method
Get rat 40, be divided into 4 groups at random, Normal group, model control group, high dose group (135mg/kg, compound concentration is 2.7%); Low dose group (67.5mg/kg, compound concentration is 1.35%).Administration group successive administration 3 days, after last administration 1 hour, each treated animal lumbar injection pentobarbital sodium (45mg/kg) is anaesthetized, dividing vein, Injection of Adrenaline (0.07g/kg), cause acute pulmonary vascular resistance to increase Animal Model of Pulmonary Edema in Piglets, its Animal performance is: breathe and weaken gradually, nasal cavity flows out foam blood and slime, and heart beating weakens.Dead after tens minutes, take lungs immediately and weigh, calculate Lung Exponent=lung weight in wet base/body weight * 100, moisture content of lung=(lung weight in wet base-lung dry weight)/lung weight in wet base * 100; Get lung upper left leaf formalin to fix, do histopathologic examination.
3. result statistics
Lung Exponent and moisture content of lung, T inspection between statistical analysis employing group, with P < 0.05 for difference has statistical significance.
4. result
Table 6 is on the impact (x ± s) of Animal Model of Pulmonary Edema in Piglets Lung Exponent and moisture content of lung
Note: compare * * P < 0.01 with normal group; △ P < 0.05 is compared with model group.
Table 7 is on the impact of acute lung edema model Pulmonary lesions
Note: grade score value :-(1 point) ,+(2 points), ++ (3 points), +++ (4 points)
Table 6 result shows, model group animal increases because of pulmonary vascular resistance, there is acute lung edema and Lung Exponent and moisture content of lung are obviously increased, compare with normal group and have significant difference (P<0.01), high dose group Lung Exponent, moisture content of lung obviously reduce, compare with model group (P < 0.05), low dose group has reduction trend, and statistical procedures is meaningless.
Table 7 histopathologic examination result shows, Normal group lung tissue is normal, and blood vessel is without expansion, and without edematous fluid accumulation around blood vessel, grade integration is 1, and total value is 10; Model group animal all sees hemorrhagic inflammation and edema, severe pathological changes animal (+++) level, and total mark value is 36; High dose group animal integrated value is 28, and low dose group integrated value is 30.
Conclusion: test the effect that confirmation this product have treatment and prevention pulmonary heart disease, can be used for preparing the medicine for the treatment of and preventing pulmonary heart disease for above two.
Although the specific embodiment of the present invention has obtained detailed description, it will be understood to those of skill in the art that.According to disclosed all instructions, can carry out various amendment and replacement to those details, these change all within protection scope of the present invention.Four corner of the present invention is provided by claims and any equivalent thereof.
Claims (15)
1. Rhizoma Drynariae, Rhizoma Drynariae extract or the compositions that comprises Rhizoma Drynariae extract are preparing the purposes prevented and/or treated in the medicine of pulmonary heart disease.
2. the purposes of claim 1, described pulmonary heart disease comprises acute pulmonary heart disease and chronic cardiopulmonary disease.
3. the purposes of claim 1, described pulmonary heart disease is caused by following reason: pulmonary infarction, adult respiratory distress syndrome, chronic obstructive pulmonary disease, primary pulmonary hypertension, bronchial asthma, wound or postoperative lung tissue disappearance, Pierre Robin syndrome, whole latter stage pneumoconiosis, sarcoidosis, obstructive sleep apnea (treatment), interstitial lung disease, drepanocytemia, pulmonary branches trachea abnormal development (neonate) or serious kyphosis.
4. the purposes of claim 1, in described Rhizoma Drynariae extract, general flavone content is 30-100%, such as, be 40-100%, then is such as 40-65%, then is such as 50-65%, then is such as 50-65%.
5. the purposes of claim 1, in described Rhizoma Drynariae extract, the content of naringin is 20-100%, such as, be 20-45%, then is such as 20-40%, then is such as 20-38%, then is such as 30-40%.
6. the purposes of claim 1, wherein said Rhizoma Drynariae extract prepares by the following method:
1) by Rhizoma Drynariae pulverizing medicinal materials, with water or alcohol or its mixture extracting;
2) extracting solution resin absorption;
3) having adsorbed the resin water of extract or alcohol or its mixture eluting.
7. the purposes of claim 6, wherein step 1) in carry out extracting with water.
8. the purposes of claim 6, wherein step 1) middle alcohol/aqueous mixtures carries out extracting.
9. the purposes of claim 6 or 8, in described alcohol/aqueous mixtures, alcohol content is 40-90% weight.
10. the purposes of claim 6,8 or 9, described alcohol is selected from methanol and ethanol.
The purposes of 11. claim 6, wherein step 2) in resin be macroporous adsorbent resin.
The purposes of 12. claim 6 or 11, wherein step 3) in first wash with water, then use alcohol/aqueous mixtures eluting.
The purposes of 13. claim 12, wherein step 1) middle alcohol/aqueous mixtures carries out extracting.
The purposes of 14. claim 12 or 13, in described alcohol/aqueous mixtures, alcohol content is 40-90% weight.
The purposes of 15. any one of claim 12-14, described alcohol is selected from methanol and ethanol.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1310000A (en) * | 2001-02-19 | 2001-08-29 | 孟庆云 | Combined Chinese and Western medicine for treating cardiopulmonary disease in catabasis |
| CN100418521C (en) * | 2000-12-29 | 2008-09-17 | 北京岐黄制药有限公司 | Gusuibu extracts for trvating osteoporosis and method for extracting same |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100418521C (en) * | 2000-12-29 | 2008-09-17 | 北京岐黄制药有限公司 | Gusuibu extracts for trvating osteoporosis and method for extracting same |
| CN1310000A (en) * | 2001-02-19 | 2001-08-29 | 孟庆云 | Combined Chinese and Western medicine for treating cardiopulmonary disease in catabasis |
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| Title |
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| 王维信等: "骨碎补双氢黄酮甙对心血管系统的药理作用", 《中国药学杂志》 * |
| 瞿岳云等: "《中医补益全书 第2辑 珍藏本》", 31 January 2011 * |
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