CN1868500A - Medicine composition contg. tetramethylpyrazine, prepn. method and use thereof - Google Patents
Medicine composition contg. tetramethylpyrazine, prepn. method and use thereof Download PDFInfo
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- CN1868500A CN1868500A CN 200610087405 CN200610087405A CN1868500A CN 1868500 A CN1868500 A CN 1868500A CN 200610087405 CN200610087405 CN 200610087405 CN 200610087405 A CN200610087405 A CN 200610087405A CN 1868500 A CN1868500 A CN 1868500A
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Abstract
A medicinal composition used to prepare the medicines for treating the ischemic cardiovascular and cerebrovascular diseases contains the chuanxiongzine and the active component. Its preparing process is also disclosed.
Description
Technical field
The invention belongs to the pharmaceutical technology field, be specifically related to a kind of pharmaceutical composition that contains ligustrazine and preparation method thereof and purposes, more particularly, relate to a kind of pharmaceutical composition that forms by ligustrazine and Flos Carthami combination of active principles and preparation method thereof and the application aspect preparation treatment ischemic cardio cerebrovascular diseases medicine.
Technical background
Ligustrazine is to extract the alkaloid monomer that obtains from the Chinese medicine Rhizoma Chuanxiong, its hydrochlorate commonly used and phosphate.Ligustrazine hydrochloride and ligustrazine phosphate are white or off-white color crystalline powder, have blood vessel dilating, increase coronary blood flow, cerebral blood flow and microcirculation improvement, increase myocardial contraction, control ischemia, anoxia and pour into the pharmacological actions such as cell injury that cause again.Ligustrazine absorbs and drains rapidly, can pass through blood-CSF barrier.The clinical ischemic cerebrovascular (as cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism) that is used for.
Flos Carthami is the dried floral of Compositae Flos Carthami, and acrid in the mouth, temperature have promoting blood circulation to restore menstrual flow, blood-activating analgetic, the effect of promoting blood circulation and detoxication.Mainly contain flavone compound, fatty acid, pigment, volatile oil, polyacetylene and other compositions.Wherein, flavone compound mainly is made up of carthamone, neocarthamin, nimbecetin, Quercetin, 6-hydroxyl-nimbecetin, astragaloside, quercimeritrin, nimbecetin-3-rutinoside and rutin, Quercetin-3-glucoside etc.Fatty acid is unsaturated fatty acids such as oleic acid, linoleic acid, Palmic acid, myristic acid, lauric acid, two Palmic acids, glyceride.Pigment mainly comprises Carthamus yellow and red pigment.Volatile oil mainly is low fatty acid and a small amount of aromatic ester and alkane.Polyacetylene is mainly 3 (suitable), 11 (instead)-and 3 (instead)-13 carbon-1,3,11-triolefin-5,7,9-three alkynes.In addition, also contain nonacosane, B-sitosterol-3-O-glucoside.Not only contain a great number of elements such as potassium, sodium, chlorine during Flos Carthami is spent, but also be rich in trace element such as chromium, manganese, zinc, molybdenum.Still contain materials such as polysaccharide and adenosine in addition.Flos Carthami has following pharmacological action: 1, the effect in excited uterus; 2, bring high blood pressure down, the effect of blood fat; 3, the effect of anticoagulation, thrombosis; 4, to the influence of cardiac function and blood vessel; 5, antiinflammatory action; 6, analgesia and calm effect; 7, anti-aging effects.
Application number is the prescription medicine that the patent documentation of CN03140467.7 discloses ligustrazine and derivant and Flos Carthami effective ingredient thereof, still the further information of unexposed in an embodiment both prescriptions, preparation method etc.
Document [be coated with Lignum Pini Nodi, etc.The red injection in river merges radiotherapy nasopharyngeal carcinoma late result observation.The contemporary Chinese medical journal, 1995,5 (4): 27] the red injection in river is disclosed, wherein every ml contains Rhizoma Chuanxiong 1g, Flos Carthami 0.6g, but does not disclose any preparation method, can't make final products to those skilled in the art.
The different places of production of Rhizoma Chuanxiong, flos carthami, the crude drug mass discrepancy in different picking seasons are bigger, and the difference of extraction process makes that the content of effective difference in the preparation is very big in addition, the strict control of difficult quality.
Summary of the invention
At above the deficiencies in the prior art, research worker of the present invention is through a large amount of tests, and preparing with ligustrazine and Flos Carthami effective ingredient is active component, according to a certain weight ratio, and the good pharmaceutical composition of curative effect.Pharmaceutical composition of the present invention makes each effective ingredient in Synergistic, and quality is easy to control, can reduce the generation of untoward reaction.
An object of the present invention is to disclose a kind of pharmaceutical composition of forming by ligustrazine and Flos Carthami effective ingredient.
Another object of the present invention is the preparation method of open aforementioned pharmaceutical compositions.
In the pharmaceutical composition of the present invention, when ligustrazine weight is 5-20 times of safflower effective ingredients weight, has the effect of Synergistic.
In the aforementioned pharmaceutical compositions, when ligustrazine weight was 10-15 times of safflower effective ingredients weight, the effect of Synergistic was better.
In the aforementioned pharmaceutical compositions, when ligustrazine weight was 10 times of safflower effective ingredients weight, the effect of Synergistic was best.
Ligustrazine in the aforementioned pharmaceutical compositions is its derivant, comprises ligustrazine hydrochloride and/or ligustrazine phosphate.
Above-mentioned safflower effective ingredients is preferably the pigment chemical compound.
Above-mentioned safflower effective ingredients, more preferably Carthamus yellow.
Above-mentioned safflower effective ingredients most preferably is S-A Hydroxysafflor yellow A.
Certainly, above-mentioned safflower effective ingredients can also comprise the flavone compound and the volatile oil of Flos Carthami.
Above-mentioned flavone compound comprises carthamone, neocarthamin, nimbecetin, Quercetin, 6-hydroxyl-nimbecetin, astragaloside, quercimeritrin, nimbecetin-3-rutinoside, rutin, Quercetin-3-glucoside etc.
Above-mentioned ligustrazine hydrochloride and ligustrazine phosphate can adopt the raw material that meets medicinal standard.
Prior art can effectively be extracted and purification effective ingredient in the Flos Carthami or position, and the product purity that obtains can reach 90% or higher.
Therefore, preferably, directly adopt commercially available or purity that known method extracts to make up greater than 50% effective site (Flos Carthami total flavone, Carthamus yellow) greater than 90% S-A Hydroxysafflor yellow A or purity.
Pharmaceutical composition of the present invention is prepared into pharmaceutical preparation according to conventional method.
The dosage form of pharmaceutical preparation of the present invention can be oral formulations and ejection preparation.Wherein oral formulations comprises tablet, capsule, pill, syrup, granule, oral solution, oral suspensions or Orally taken emulsion.Injection comprises small-volume injection, bulk capacity injection, injectable powder and lyophilized injectable powder.
Can add pharmaceutically acceptable additives as required in the various dosage form of the present invention, for example antioxidant, solubilizing agent, isoosmotic adjusting agent, excipient etc.
Many effective ingredient of Chinese medicine are oxidized easily, can add antioxidant, for example sodium sulfite, sodium sulfite, sodium thiosulfate etc.
If contain fat-soluble effective ingredient in the injection,, can add solubilizing agents such as tween 80 in order to increase its dissolubility.
Be used to regulate the isoosmotic adjusting agent of osmotic pressure, be usually used in intravenous injection and infusion solutions, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc. are preferably sodium chloride and/or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.
In tablet, can add filler, wetting agent, binding agent, disintegrating agent, lubricant etc. as required.Filler can be starch, microcrystalline Cellulose, pregelatinized Starch etc.Wetting agent can be water and/or ethanol.Binding agent can be polyvidone, starch slurry, cellulose etc.Disintegrating agent can be polyvinylpolypyrrolidone, CC-Na, starch or CMC-Na etc.Lubricant can be Pulvis Talci, stearic acid, magnesium stearate calcium, magnesium stearate etc.
In granule, can add filler, wetting agent, binding agent etc. as required.
Can add antiseptic, correctives in the solution type liquid agent.
Also should add dense aqueous sucrose solution in the syrup.
Can add suspending agent, wetting agent, flocculating agent etc. as required in the suspensoid.Suspending agent can be arabic gum, sodium alginate, agar, polyvidone, cellulose family, carbopol, sodium acrylate.
Can add emulsifying agent, antiseptic, correctives etc. in the Orally taken emulsion.
Research worker of the present invention has been carried out a large amount of experiments, and ligustrazine and Flos Carthami effective ingredient (is index with the S-A Hydroxysafflor yellow A) (carrying out according to the method among the pharmacology embodiment 1) weight proportion has been carried out preferably.Experimental result sees Table 1.
The experiment of table 1 active component proportion optimization
| Ligustrazine: safflower effective ingredients (g/g) | Pharmacological action |
| 30∶1 25∶1 20∶1 15∶1 10∶1 5∶1 1∶1 0.5∶1 | ± ± + ++ +++ + ± ± |
Annotate: ± expression pharmacological action is poor; + expression pharmacological action is general; ++ the expression pharmacological action is better; +++expression pharmacological action is best.
By above-mentioned experimental result as can be seen, when the ligustrazine weight portion was 5-20 times of safflower effective ingredients weight portion, synergy was general; Wherein when the ligustrazine weight portion was 10-15 times of safflower effective ingredients weight portion, synergy was better; Wherein when the ligustrazine weight portion was 10 times of safflower effective ingredients weight portion, synergy was best.
Pharmaceutical composition of the present invention can be given full play to the synergism of each component, active constituent content is clear and definite, substantially do not contain the useless or deleterious composition of human body, can be fit to the preparation various injectable dosage forms strict to pharmaceutical purity especially, the performance injection is than the advantage of other dosage form instant effects.
Various dosage form of the present invention has fundamentally solved the long-standing drug safety problem of injection, especially is suitable for treating cardiovascular and cerebrovascular disease.
Pharmaceutical composition of the present invention is the compound preparation that ligustrazine and Flos Carthami effective ingredient forms by the special ratios assembly, and its absorption and drainage can be passed through blood-cerebrospinal fluid barrier rapidly.By the two additional mutually body that acts synergistically on, give full play to blood circulation promoting and blood stasis dispelling, anti-platelet aggregation is arranged, blood vessel dilating, the microcirculation improvement effect, the smelting that is applicable to ischemic cardio cerebrovascular diseases is treated, as cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism, cerebral vasospasm, brain insufficiency, alzheimer disease, parkinson, apoplexy, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, angina pectoris, myocardial infarction.Also can be used for the microcirculation pathological changes that hepatic fibrosis, diabetes cause, vasculitis etc.
Pharmacology embodiment
Research worker of the present invention with the application number be lyophilized injectable powder in the CN200510087001.5 patent documentation as positive control drug, the present invention has been carried out following pharmacodynamic experiment.
1, the influence of anoxia in mice endurance is tested
Get 30 of healthy Kunming mouses, body weight 20～24g.Be divided into the normal control group at random, positive controls, medicine group of the present invention.Every group 10, male and female half and half, sub-cage rearing.Each organizes respectively that intravenous injection gives relative medicine, and matched group is given the normal saline of respective volume, and 1 time/d, 7d continuously.After the last administration 1 hour, it was the 150ml port grinding bottle that mice is placed volume respectively, in put the 15g sodica calx, its time-to-live of airtight observation.The results are shown in Table 2.
The influence of table 2 pair mice normobaric hypoxia (X ± S)
| Group | Mus number (only) | Mean survival time (min) |
| Normal control group positive controls medicine group of the present invention | 10 10 10 | 16.88±3.14 27.26±3.08 ** 26.75±3.25 ** |
Annotate: compare with the normal control group:
*P＜0.05;
*P＜0.01.
2, to the anoxybiotic protective effect experiment of mouse cardiac muscle
Get 30 of healthy Kunming mouses, body weight 18～22g is divided into 3 groups at random, is divided into the normal control group at random, positive drug group, medicine group of the present invention.Every group of male and female half and half, sub-cage rearing.Each organizes respectively that intravenous injection gives relative medicine, and matched group is given the normal saline of respective volume.Medication: 1 time/day, continuous 7 days.Back fixation was separated trachea with urethane 1.2g/kg intraperitoneal injection of anesthesia in 1 hour after the last administration, with the bulldog clamp folder pipe of holding one's breath, observed electrocardio with electrocardiogram equipment, and write down the little mousetrap with stopwatch and hold one's breath time of Guan Houzhi electrocardio disappearance.The results are shown in Table 3.
The anoxybiotic influence of table 3 pair mouse cardiac muscle (X ± S)
| Group | Mus number (only) | Mean survival time (min) |
| Normal control group positive controls medicine group of the present invention | 10 10 10 | 6.94±0.88 12.17±1.03 ** 11.84±1.12 ** |
Annotate: compare with the normal control group:
*P＜0.05;
*P＜0.01.
3, the influence that the rat thrombus in vivo is formed
Rat is divided into 3 groups at random, 10 every group, is respectively the normal control group, positive drug group, medicine group of the present invention.Each organizes respectively that vein gives relative medicine, and matched group is given the normal saline of respective volume, control group administered physiological saline.Every day 1 time, successive administration 7 days, after the last administration 1 hour, rat is used 10% chloral hydrate, it is fixing to press 0.3g/kg body weight anesthesia back, separates left common carotid artery, on the thrombosis instrument with 2mA galvanism blood vessel 7min after, the record thrombus formation time.The results are shown in Table 4.
The influence that table 4 pair rat thrombus in vivo forms (X ± S)
| Group | Mus number (only) | Thrombus formation time (min) |
| Normal control group positive controls medicine group of the present invention | 10 10 10 | 634.2±70.2 748.3±71.4 ** 715.6±66.8 ** |
Annotate: compare with the normal control group:
*P＜0.05;
*P＜0.01.
By above-mentioned pharmacological evaluation as can be seen, pharmaceutical preparation of the present invention has the effect of good treatment cardiovascular and cerebrovascular disease.
The specific embodiment
Further describe the present invention with embodiment below, help understanding, but described embodiment only is used to illustrate the present invention rather than restriction the present invention the present invention and advantage thereof, better effects if.
Commercially available safflower effective ingredients: the purity of one-component is more than 90%; The purity of effective site is more than 50%.
Embodiment 1
Take by weighing commercially available S-A Hydroxysafflor yellow A 10g, ligustrazine phosphate 100g, can be made into the 100000ml medicinal liquid, finally make 400 bottles of bulk capacity injections (specification is the 250ml/ bottle).In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, drop into 900g sodium chloride, fully stir and make dissolving fully, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added above-mentioned raw materials in dilute preparing tank, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring pH is 4.8 ± 0.2, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is filled nitrogen by bottle during embedding in infusion bottle, sterilization promptly gets infusion products.
Embodiment 2
Take by weighing commercially available S-A Hydroxysafflor yellow A 8g, Carthamus yellow 7g, Flos Carthami total flavone 5g, ligustrazine hydrochloride 100g, can be made into the 100000ml medicinal liquid, finally make 400 bottles of bulk capacity injections (specification is the 250ml/ bottle).In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, drop into 900g sodium chloride, fully stir and make dissolving fully, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added above-mentioned raw materials in dilute preparing tank, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 4.8 ± 0.2, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is filled nitrogen by bottle during embedding in infusion bottle, sterilization promptly gets infusion products.
Embodiment 3
Take by weighing commercially available S-A Hydroxysafflor yellow A 4g, Carthamus yellow 1g, ligustrazine phosphate 100g, can be made into the 100000ml medicinal liquid, finally make 400 bottles of bulk capacity injections (specification is the 250ml/ bottle).In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, drop into 900g sodium chloride, fully stir and make dissolving fully, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added above-mentioned raw materials in dilute preparing tank, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 4.8 ± 0.2, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is filled nitrogen by bottle during embedding in infusion bottle, sterilization promptly gets infusion products.
Embodiment 4
Take by weighing commercially available S-A Hydroxysafflor yellow A 5g, volatile oil 1g, ligustrazine hydrochloride 90g, can be made into the 2000ml medicinal liquid, finally make 1000 of small-volume injections.In preparing tank, add an amount of 48 ℃ of waters for injection, add above-mentioned raw materials again, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, add an amount of tween 80, add water for injection to the dosing amount, transferring PH is 4.5, and with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, embedding is in ampoule, ampoule fills nitrogen by propping up during embedding, and sterilization promptly gets small-volume injection.
Embodiment 5
Take by weighing commercially available S-A Hydroxysafflor yellow A 12g, ligustrazine phosphate 100g, can be made into the 100000ml medicinal liquid, finally make 400 bottles of bulk capacity injections (specification is the 250ml/ bottle).In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, drop into 900g sodium chloride, fully stir and make dissolving fully, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added above-mentioned raw materials in dilute preparing tank, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 4.8 ± 0.2, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is filled nitrogen by bottle during embedding in infusion bottle, sterilization promptly gets infusion products.
Embodiment 6
Take by weighing commercially available S-A Hydroxysafflor yellow A 10g, ligustrazine hydrochloride 120g, can be made into the 100000ml medicinal liquid, finally make 400 bottles of bulk capacity injections (specification is the 250ml/ bottle).In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, drop into 900g sodium chloride, fully stir and make dissolving fully, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added above-mentioned raw materials in dilute preparing tank, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 4.8 ± 0.2, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is filled nitrogen by bottle during embedding in infusion bottle, sterilization promptly gets infusion products.
Embodiment 7
Take by weighing commercially available Carthamus yellow 10g, ligustrazine phosphate 80g, can be made into the 1000ml medicinal liquid, finally make 1000 of small-volume injections.Add an amount of 48 ± 2 ℃ of waters for injection in preparing tank, add above-mentioned raw materials again, fully stirring is dissolved it fully, add the Dextran 40 excipient, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, add water for injection to the dosing amount, transferring PH is 4.8, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, medicinal liquid fill behind end-filtration (loading amount 1.0ml/ props up), the freeze-dried powder product is made in lyophilizing behind the false add plug.
Embodiment 8
Take by weighing commercially available S-A Hydroxysafflor yellow A 8g, ligustrazine phosphate 100g, can finally make 1000 in tablet.Will above-mentioned raw materials mix with 80 gram starch mixings after granulate with starch slurry, cross 20 mesh sieve granulate, drying adds 1 gram magnesium stearate compacting in flakes, promptly gets tablet.
Embodiment 9
Take by weighing commercially available Flos Carthami total flavone and Flos Carthami flavochrome 10g, ligustrazine phosphate 100g altogether, can finally make capsule.Behind above-mentioned raw materials and 80 gram starch, 80 gram Pulvis Talci mixings, cross 100 mesh sieves, encapsulated, capsule.
Claims (10)
1, a kind of pharmaceutical composition that contains ligustrazine is characterized in that, in the pharmaceutical composition ligustrazine weight be safflower effective ingredients weight 5-20 doubly.
2, pharmaceutical composition according to claim 1 is characterized in that, in the pharmaceutical composition ligustrazine weight be safflower effective ingredients weight 10-15 doubly.
3, pharmaceutical composition according to claim 2 is characterized in that, ligustrazine weight is 10 times of safflower effective ingredients weight in the pharmaceutical composition.
According to the described pharmaceutical composition of one of claim 1-3, it is characterized in that 4, wherein said ligustrazine is ligustrazine hydrochloride and/or ligustrazine phosphate.
According to the described pharmaceutical composition of one of claim 1-4, it is characterized in that 5, wherein said safflower effective ingredients is a Carthamus yellow.
6, pharmaceutical composition according to claim 5 is characterized in that, wherein said safflower effective ingredients is a S-A Hydroxysafflor yellow A.
According to the described pharmaceutical composition of one of claim 1-6, it is characterized in that 7, wherein said safflower effective ingredients also comprises one or both the mixture in flavone compound and the volatile oil.
8, according to the described pharmaceutical composition of one of claim 1-7, it is characterized in that, can be prepared into oral formulations and ejection preparation; Wherein oral formulations comprises tablet, capsule, pill, syrup, granule, oral solution, oral suspensions or Orally taken emulsion; Injection comprises small-volume injection, bulk capacity injection, injectable powder and lyophilized injectable powder.
9, pharmaceutical composition according to claim 8 is characterized in that, also contains pharmaceutically acceptable pharmaceutic adjuvant in the described pharmaceutical preparation.
10, the described pharmaceutical composition of one of claim 1-9 is at preparation treatment ischemic cardio cerebrovascular diseases, as cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism, cerebral vasospasm, brain insufficiency, alzheimer disease, parkinson, apoplexy, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, angina pectoris, myocardial infarction disease, in the microcirculation pathological changes that preparation treatment hepatic fibrosis, diabetes cause, the application of each disease medicament aspect of vasculitis.
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| CN 200610087405 CN1868500A (en) | 2006-06-09 | 2006-06-09 | Medicine composition contg. tetramethylpyrazine, prepn. method and use thereof |
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| CN 200610087405 CN1868500A (en) | 2006-06-09 | 2006-06-09 | Medicine composition contg. tetramethylpyrazine, prepn. method and use thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103039865A (en) * | 2012-12-28 | 2013-04-17 | 祝凤仪 | Small red bean flour capable of invigorating blood circulation and stimulating menstrual flow and preparation method of small red bean flour |
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2006
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103039865A (en) * | 2012-12-28 | 2013-04-17 | 祝凤仪 | Small red bean flour capable of invigorating blood circulation and stimulating menstrual flow and preparation method of small red bean flour |
| CN103039865B (en) * | 2012-12-28 | 2013-09-04 | 祝凤仪 | Small red bean flour capable of invigorating blood circulation and stimulating menstrual flow and preparation method of small red bean flour |
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Open date: 20061129 |