CN102885857B - Extraction method of periplaneta americana extract for treating peptic ulcer - Google Patents
Extraction method of periplaneta americana extract for treating peptic ulcer Download PDFInfo
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Abstract
The invention provides an extraction method of a periplaneta americana extract for treating peptic ulcer, comprising the following steps of:A, crushing, B, soaking, C, extracting, D, primarily concentrating, E, degreasing, and F, secondarily concentrating. According to th invention, extraction is carried out by using the method, lots of proteins contained in periplaneta Americana can be effectively removed, and the degreasing rate is high; and moreover, 90-95% ethanol is used for soaking a coarse powder, so that preservation time is prolonged, and the yield of specific active ingredients for treating peptic ulcer is increased. Due to reasonable control on each process parameter, hydrolysis of the active ingredients for treating peptic ulcer in the extract can be prevented, and the curative effect of the medicine can be improved. With the process disclosed by the invention, the extraction method is low in production cost and high in production efficiency. Clinically applicable preparations (tablets, capsules, mixture, oral liquid, pellets, dripping pills, spray, aerosol, gels and the like) can be prepared by taking the periplaneta americana extract obtained by the method disclosed by the invention and adding proper pharmaceutical auxiliary materials, and are used for (oral-administration or spray) treatment for peptic ulcer.
Description
Technical field
The present invention relates to medical technical field, relate in particular to a kind of extracting method for the treatment of the American-cockroach-extract that digestive tract ulcer uses.
Background technology
Periplaneta americana (Periplaneta americana) is the insecticide of volume maximum in Blattidae, becomes long 29~35 millimeters of polypide, bronzing, and wing is longer than abdomen end.Feeler is very long, in the middle of pronotary, has larger butterfly brown speckle, and the trailing edge of speckle has complete yellow band stricture of vagina, originates in South America, and feeding habits are extensive, sugar and starch, contaminated food are eaten in happiness.
Periplaneta americana is traditional Chinese crude drug, is used as medicine with adult.Salty in the mouth cold in nature, poisonous, there is acid, have dissipating blood stasis, the function such as removing food stagnancy, removing toxic substances, diuretic, detumescence.Modern study is found, periplaneta americana epidermis contains the elements such as sclerotin, chitin, bromine, zinc, nickel, violent, potassium, calcium, titanium, chlorine, sulfur, silicon, aluminum, magnesium, muscle is hydrolyzed 13 seed amino acids, health is preserved the plain B1 of micro-life, B2, nicotinic acid and ascorbic acid etc., lymph is containing trehalose, trehalase, glycoprotein, inositol, protocatechuic acid Fructus Vitis viniferae glycoside etc., all containing ergothioneine, 1-methyl-2-pyridinium carboxylate, trigonelline, glycine, betanin, anus alkali, trimethylamine, adenine etc.
Periplaneta americana is dried polypide extract, contain WHF (polyalcohols, epidermal growth factor), sticky propylhomoserin, sticky sugared propylhomoserin and several amino acids isoreactivity material, having antiinflammatory, detumescence, promotion cell proliferation and new granulation tissue increases, accelerate disease damage tissue repair, accelerate slough and come off, improve the effects such as body's immunity.
Periplaneta americana all has application at aspects such as treatment burn and scald, oral ulcer, gastric ulcer, hemorrhoid, anal fissure, gastritis and peptic gastric ulcer, gastric ulcer colitis, gynaecopathia, diaper rash, allergic rhinitis, antitumor at present, but, current application mostly is Chinese medicine application mode, certain applications are dry adult parts as medicament composing prescription, and part is that its extract and other drug compatibility are used.
Although there are some open to the extracting method of American-cockroach-extract,, the contained composition of periplaneta americana is more, also difference to some extent of the composition that different extracting modes obtains, extract obtained also have different effects to different diseases.But, current disclosed technology, the technical matters that is used for the treatment of certain disease for the specific active ingredient extraction of periplaneta americana is still immature, and deep processing and the depth extraction of carrying out for treatment specified disease will become new development trend.
Summary of the invention
The object of this invention is to provide a kind of extracting method for the treatment of the American-cockroach-extract that digestive tract ulcer uses, the process route adopting can make in periplaneta americana, the specific active ingredient for the treatment of digestive tract ulcer to be assembled, thereby improves the therapeutic effect of simple American-cockroach-extract to treatment digestive tract ulcer.
The present invention adopts following technology to realize above-mentioned purpose:
The extracting method of the American-cockroach-extract that treatment digestive tract ulcer is used, comprises the following steps:
A, pulverizing: dry periplaneta americana polypide is pulverized, cross 24 mesh sieves, make periplaneta americana coarse powder;
B, immersion: the soak with ethanol by steps A gained periplaneta americana coarse powder by concentration 90%~95%, make ethanol liquid level exceed the airtight preservation of coarse powder liquid level 5~10cm, make coarse powder mixed liquor;
C, extraction: step B gained coarse powder mixed liquor is carried out to reflux, extract, 3~5 times at the temperature of 70~85 ℃, when coarse powder mixed liquor is extracted for the first time, the ethanol of 5~8 times of amount concentration 90%~95% of overstriking grain weight amount, extraction time is 4~6 hours; Each ethanol that extracts 3~6 times of amount concentration 90%~95% of overstriking grain weight amount for the second time, extraction time is 3~5 hours; Merge extractive liquid,, filters to obtain ethanol extract;
D, one-level are concentrated: by step C gained ethanol extract concentrating under reduced pressure under the condition of 50~60 ℃ of vacuum-0.05~-0.06MPa, temperature, to proportion be 1.05~1.15 o'clock, obtain ethanol concentrated solution;
E, defat: the purified water that step D gained ethanol concentrated solution is added to 7~10 times of amounts of ethanol concentrated solution weight, behind warming while stirring to 85~95 ℃, stir 10~60 minutes, mixing speed is 20~60 revs/min, and then insulation leaves standstill and within 1~5 hour, makes profit layering;
F, secondary concentrate: step e gained lower layer of water liquid is emitted, after filter paper filtering, filtrate is concentrating under reduced pressure under 60~80 ℃ of temperature, vacuum-0.05~-0.06MPa condition, and being concentrated into proportion is 1.25~1.35 o'clock, must treat the American-cockroach-extract that digestive tract ulcer is used.
Preferably, step C can be by the following technical solutions: step B gained coarse powder mixed liquor is carried out to reflux, extract, 4 times at the temperature of 75~80 ℃, when coarse powder mixed liquor is extracted for the first time, add the ethanol of 5 times of amount concentration 92% of coarse powder, extraction time is 5 hours; Each ethanol that adds 4 times of amount concentration 92% of coarse powder that extracts for the second time, extraction time is 4 hours, merges four times extracting solution, filters to obtain ethanol extract.
More preferably, step e can be by the following technical solutions: step D gained ethanol concentrated solution is added to the purified water of 8 times of amounts of ethanol concentrated solution weight, behind warming while stirring to 85~95 ℃, stir 40 minutes, mixing speed is 40 revs/min, and then insulation leaves standstill and within 4 hours, makes profit layering.
beneficial effect of the present invention:
The method of the invention is devoted to be developed to specified disease, specific active ingredient application direction by pure Chinese medicine application, the process route adopting can make in periplaneta americana, the specific active ingredient for the treatment of digestive tract ulcer to be assembled, thereby improves the therapeutic effect of simple American-cockroach-extract to treatment digestive tract ulcer.The beneficial effect that concrete technology has is as follows:
1, adopt this process route to extract, can effectively remove a large amount of protein that contain in periplaneta americana, grease removal rate is high, and the extract oils and fats content (ligroin extraction) obtaining is in A(trap)/W(weight) must not cross 0.30.
2, with the soak with ethanol coarse powder of concentration 90%~95%, not only can prevent that microbial reproduction from causing periplaneta americana coarse powder putrid and deteriorated, extend the holding time, and can improve the specific active ingredient yield for the treatment of digestive tract ulcer.
3, adopt technological process of the present invention, the specific active ingredient yield content for the treatment of digestive tract ulcer can be up to 13%~22%, and adopt the medicine for the treatment of digestive tract ulcer prepared by this extract, and it can reach 55%~70% to the cure rate of digestive tract ulcer, and total effective rate can reach 97%~99%.Wherein, can reach 60%~75% to oral ulcer cure rate, total effective rate can reach more than 99%; Can reach 45%~65% to gastric and duodenal ulcers cure rate, total effective rate can reach more than 95%.
4, adopt process route of the present invention to extract, reasonable because of each process parameter control, therefore can prevent the active substance hydrolysis to treatment digestive tract ulcer in extract, improve its curative effect of medication.
5, the present invention's process route used is brief, can reduce production costs, and enhances productivity.
6, get foregoing invention gained American-cockroach-extract, add appropriate pharmaceutical necessities, can make applicable clinically preparation (tablet, capsule, mixture, oral liquid, pellet, drop pill, spray, aerosol, gel etc.), for the treatment of digestive tract ulcer (for oral administration or spraying).
Specific embodiment
embodiment 1
The extracting method of the American-cockroach-extract that treatment digestive tract ulcer is used, comprises the following steps:
A, pulverizing: periplaneta americana polypide dry 200Kg is pulverized, cross 24 mesh sieves, make periplaneta americana coarse powder;
B, immersion: the soak with ethanol by steps A gained periplaneta americana coarse powder by concentration 95%, make ethanol liquid level exceed the airtight preservation of coarse powder liquid level 5cm, make coarse powder mixed liquor;
C, extraction: step B gained coarse powder mixed liquor is dropped in extraction pot, carry out reflux, extract, at the temperature of 70~85 ℃ 3 times, when coarse powder mixed liquor is extracted for the first time, add the ethanol of 1000Kg concentration 95%, extraction time is 4 hours; Each ethanol that adds 600Kg concentration 95% that extracts for the second time, extraction time is 3 hours; Merge extractive liquid,, filters to obtain ethanol extract;
D, one-level are concentrated: step C gained ethanol extract is put into haplo-effect concentrator, concentrating under reduced pressure under the condition of 50~60 ℃ of vacuum-0.05~-0.06MPa, temperature, to proportion be 1.08 o'clock, obtain ethanol concentrated solution;
E, defat: step D gained ethanol concentrated solution is moved in degreasing tank, add 380Kg purified water, behind warming while stirring to 85~95 ℃, stirs 10 minutes, mixing speed is 60 revs/min, then insulation is standing makes profit layering for 1 hour;
F, secondary concentrate: step e gained lower layer of water liquid is emitted, after filter paper filtering, filtrate moves into concentrator, concentrating under reduced pressure under 60~80 ℃ of temperature, vacuum-0.05~-0.06MPa condition, being concentrated into proportion is 1.28 o'clock, must treat the American-cockroach-extract 25.2Kg that digestive tract ulcer is used.
Adopt above-mentioned technological process, mainly for the production of the drug extract for the treatment of (oral ulcer, gastric and duodenal ulcers), extract yield reaches 12.6%, each technique can be up to 16.3% to the specific active ingredient yield content for the treatment of (oral ulcer, gastric and duodenal ulcers), its cure rate to (oral ulcer, gastric and duodenal ulcers) can reach 63.4%, and total effective rate can reach 98.9%.Fat content (ligroin extraction) counts 0.24 with A/W.
embodiment 2
The extracting method of the American-cockroach-extract that treatment digestive tract ulcer is used, comprises the following steps:
A, pulverizing: periplaneta americana polypide dry 200Kg is pulverized, cross 24 mesh sieves, make periplaneta americana coarse powder;
B, immersion: the soak with ethanol by steps A gained periplaneta americana coarse powder by concentration 92%, make ethanol liquid level exceed the airtight preservation of coarse powder liquid level 8cm, make coarse powder mixed liquor;
C, extraction: step B gained coarse powder mixed liquor is dropped in extraction pot, at the temperature of 70~85 ℃, carry out reflux, extract, 4 times, when coarse powder mixed liquor is extracted for the first time, the ethanol of 1000Kg concentration 92%, extraction time is 5 hours; Each ethanol that adds 800Kg concentration 92% that extracts for the second time, extraction time is 4 hours; Merge extractive liquid,, filters to obtain ethanol extract;
D, one-level are concentrated: step C gained ethanol extract is put into haplo-effect concentrator, concentrating under reduced pressure under the condition of 50~60 ℃ of vacuum-0.05~-0.06MPa, temperature, to proportion be 1.11 o'clock, obtain ethanol concentrated solution;
E, defat: step D gained ethanol concentrated solution is moved in degreasing tank, add 416Kg purified water, behind warming while stirring to 85~95 ℃, stirs 40 minutes, mixing speed is 40 revs/min, then insulation is standing makes profit layering for 4 hours;
F, secondary concentrate: step e gained lower layer of water liquid is emitted, after filter paper filtering, filtrate moves into concentrator, concentrating under reduced pressure under 60~80 ℃ of temperature, vacuum-0.05~-0.06MPa condition, being concentrated into proportion is 1.32 o'clock, must treat the American-cockroach-extract 31.4Kg that digestive tract ulcer is used.
Adopt above-mentioned technological process, mainly for the production of the drug extract for the treatment of (oral ulcer, gastric and duodenal ulcers), extract yield reaches 15.7%, each technique can be up to 17.1% to the specific active ingredient yield content for the treatment of (oral ulcer, gastric and duodenal ulcers), its cure rate to (oral ulcer, gastric and duodenal ulcers) can reach 59.5%, and total effective rate can reach 97.2%.Fat content (ligroin extraction) counts 0.19 with A/W.
embodiment 3
The extracting method of the American-cockroach-extract that treatment digestive tract ulcer is used, comprises the following steps:
A, pulverizing: periplaneta americana polypide dry 200Kg is pulverized, cross 24 mesh sieves, make periplaneta americana coarse powder;
B, immersion: the soak with ethanol by steps A gained periplaneta americana coarse powder by concentration 90%, make ethanol liquid level exceed the airtight preservation of coarse powder liquid level 10cm, make coarse powder mixed liquor;
C, extraction: step B gained coarse powder mixed liquor is dropped in extraction pot, at the temperature of 70~85 ℃, carry out reflux, extract, 5 times, when coarse powder mixed liquor is extracted for the first time, the ethanol of 1600Kg concentration 90%, extraction time is 6 hours; Each ethanol that adds 1200Kg concentration 90% that extracts for the second time, extraction time is 5 hours; Merge extractive liquid,, filters to obtain ethanol extract;
D, one-level are concentrated: step C gained ethanol extract is put into haplo-effect concentrator, concentrating under reduced pressure under the condition of 50~60 ℃ of vacuum-0.05~-0.06MPa, temperature, to proportion be 1.14 o'clock, obtain ethanol concentrated solution;
E, defat: step D gained ethanol concentrated solution is moved in degreasing tank, add 430Kg purified water, behind warming while stirring to 85~95 ℃, stirs 60 minutes, mixing speed is 20 revs/min, then insulation is standing makes profit layering for 5 hours;
F, secondary concentrate: step e gained lower layer of water liquid is emitted, after filter paper filtering, filtrate moves into concentrator, concentrating under reduced pressure under 60~80 ℃ of temperature, vacuum-0.05~-0.06MPa condition, being concentrated into proportion is 1.26 o'clock, must treat the American-cockroach-extract 32.1Kg that digestive tract ulcer is used.
Adopt above-mentioned technological process, mainly for the production of the drug extract for the treatment of (oral ulcer, gastric and duodenal ulcers), extract yield reaches 16.1%, each technique can be up to 15.7% to the specific active ingredient yield content for the treatment of (oral ulcer, gastric and duodenal ulcers), its cure rate to (oral ulcer, gastric and duodenal ulcers) can reach 63.8%, and total effective rate can reach 99.1%.Fat content (ligroin extraction) counts 0.21 with A/W.
embodiment 4
Medicine prepared by the American-cockroach-extract that treatment digestive tract ulcer is used and treatment case:
Get above-mentioned (embodiment 1) American-cockroach-extract 7g, glycerol adding 100ml, sodium benzoate 2.5g, add purified water to 800ml, is heated to boiling, stirs filtered while hot, the filtrate 1000ml that adds water again.Fill becomes the mixture of 100ml/ bottle, or the oral liquid that props up of 10ml/.
Case-data and grouping: 79 examples, are diagnosed as gastric ulcer or stomach and duodenum plyability ulcer through stomach fiberendoscope; All without complication; Be divided into treatment group 45 example and matched group 34 examples.Treatment group man 28 examples, female's 17 examples; 15~62 years old age; The course of disease 6 months~17 years; Gastric ulcer 38 examples (84.4%), plyability ulcer 7 examples (15.6%).Matched group man 20 examples, female's 14 examples, 16~60 years old age; The course of disease 6 months~15 years; Gastric ulcer 26 examples (76.5%), plyability ulcer 8 examples (23.5%).
Method: matched group adopts triple therapy (the triple therapy scheme that the helicobacter pylori Collaboration on Scientific Research meeting of the whole nation, Hainan in 1999 is recommended): omeprazole 20mg+ amoxicillin 1g+ tinidazole 0.5g, every day 2 times, early, evening is bfore meals.Treatment group adds above-mentioned oral liquid 10m on treatment of control group basis to be taken, every day 3 times, sooner or later ante cibum and sleep before each 1 time, within least 40 minutes, take with first three connection medicine interval.Two groups of case medications are 2 weeks, and period in a medicine is quitted smoking, wine and vinegar-pepper irritable food.After finishing, treatment checks for 4 weeks and 1 year.
Curative effect judging standard: (1) cures: subjective symptoms and sign disappear, ulcer surface healing; (2) take a turn for the better: subjective symptoms and sign obviously alleviate, and ulcer surface dwindles more than 50%; (3) invalid: subjective symptoms and sign have no and alleviate, ulcer surface has no and dwindles; (4) recurrence: cure or the rear part or all of symptom occurring before treatment that takes a turn for the better, and through stomach fiberendoscopy pathological changes positive.(1) cure and add (2) and transfer to well effectively.
Result: treatment group is cured 30 examples (66.7%), 14 examples that take a turn for the better (31.1%), invalid 1 example (2.2%), effective percentage 97.8%.Matched group is cured 15 examples (44.1%), 13 examples that take a turn for the better (38.2%), invalid 6 examples (17.6%), effective percentage 82.4%.Treatment group cure rate is higher than matched group.
embodiment 5
Medicine prepared by the American-cockroach-extract that treatment digestive tract ulcer is used and treatment case:
Get above-mentioned (embodiment 2) American-cockroach-extract 140g, add starch 670g, dextrin 220g, add debita spissitudo alcohol soft material, granulate, dry, add magnesium stearate 2g granulate, obtain granule 1000g, by every dress 0.25g filled capsules.
Case-data and grouping: 62 examples, are diagnosed as gastric ulcer through gastroscopy, wherein male's example 41, women's 21 examples, age of onset 17~70 years old, course of disease March~7 year.Clinical manifestation: dryness of the mouth and throat, hunger but having no desire to eat, headquarters or seat of leading organs of an institute like the Chinese Academy of Sciences's dull pain, constipation with dry stool, oliguria, belch acid regurgitation, red tongue with a little fluid, thready pulse and count dialectical genus deficiency of stomach-YIN pattern of syndrome peptic ulcer.Be divided at random treatment group 35 example and matched group 27 examples.
Method: treatment group gives above-mentioned capsule oral, each 2, every day 3 times, matched group gives famotidine tablets, each 20mg, each 1 time sooner or later.And the patient of the HP positive is all added to amoxicillin, each 1g, every day 2 times, the each 0.lg of furazolidone, every day 2 times.Penicillin anaphylaxis person is not listed as this range of observation of people.All treating for two groups 4 weeks was 1 course for the treatment of, after finish 1 course for the treatment of, carried out gastroscope check.
Curative effect judging standard: gastroscopy effect: (1) cures: ulcer and around inflammation all disappear; (2) take a turn for the better: ulcer disappears, and still has inflammation; (3) effective: ulcer area dwindles >=and 50%; (4) invalid: ulcer without change or dwindle≤50%.Clinical disease curative effect: after treatment, clinical symptoms, sign disappear or substantially disappear, syndrome integration is treated front minimizing >=95% for clinical recovery; After treatment, clinical symptoms is obviously improved, and it is effective that syndrome integration reduces >=70%; After treatment, clinical symptoms takes a turn for the better, and it is effective that syndrome integration reduces >=30%; After treatment, clinical symptoms is not improved, and it is invalid that syndrome integration reduces less than 30%.
Result: treatment group and matched group are relatively gone up without significant difference (P > 0.05) in traditional Chinese medical science disease curative effect.Show that two medicines all have remarkable effect in tcm syndrome curative effect aspect improving, and see the following form 1.Relatively go up at gastroscopy effect for two groups, treatment group total effective rate reaches 94.9%, and matched group total effective rate is 85.2%, and treatment group is apparently higher than matched group, in table 2.
Table 1 liang group traditional Chinese medical science disease curative effect comparison
Group | n | Clinical recovery (%) | Effective (%) | Effectively (%) | Invalid (%) | Total effective rate (%) |
Treatment group | 35 | 9(25.7%) | 16(45.7%) | 9(25.7%) | 1(2.9%) | 97.1% |
Matched group | 27 | 6(22.2%) | 10(37.0%) | 9(33.3%) | 2(7.4%) | 92.6% |
Table 2 liang group patient gastroscopy effect comparison
Group | n | Clinical recovery (%) | Effective (%) | Effectively (%) | Invalid (%) | Total effective rate (%) |
Treatment group | 35 | 18(51.4%) | 10(28.6%) | 5(14.3%) | 2(5.7%) | 94.9% |
Matched group | 27 | 13(48.1%) | 6(22.2%) | 4(14.8%) | 4(14.8%) | 85.2% |
Claims (3)
1. the extracting method of the American-cockroach-extract that treatment digestive tract ulcer is used, is characterized in that comprising the following steps:
A, pulverizing: dry periplaneta americana polypide is pulverized, cross 24 mesh sieves, make periplaneta americana coarse powder;
B, immersion: the soak with ethanol by steps A gained periplaneta americana coarse powder by concentration 90%~95%, make ethanol liquid level exceed the airtight preservation of coarse powder liquid level 5~10cm, make coarse powder mixed liquor;
C, extraction: step B gained coarse powder mixed liquor is carried out to reflux, extract, 3~5 times at the temperature of 70~85 ℃, when coarse powder mixed liquor is extracted for the first time, the ethanol of 5~8 times of amount concentration 90%~95% of overstriking grain weight amount, extraction time is 4~6 hours; Each ethanol that extracts 3~6 times of amount concentration 90%~95% of overstriking grain weight amount for the second time, extraction time is 3~5 hours; Merge extractive liquid,, filters to obtain ethanol extract;
D, one-level are concentrated: by step C gained ethanol extract concentrating under reduced pressure under the condition of 50~60 ℃ of vacuum-0.05~-0.06MPa, temperature, to proportion be 1.05~1.15 o'clock, obtain ethanol concentrated solution;
E, defat: the purified water that step D gained ethanol concentrated solution is added to 7~10 times of amounts of ethanol concentrated solution weight, behind warming while stirring to 85~95 ℃, stir 10~60 minutes, mixing speed is 20~60 revs/min, and then insulation leaves standstill and within 1~5 hour, makes profit layering;
F, secondary concentrate: step e gained lower layer of water liquid is emitted, after filter paper filtering, filtrate is concentrating under reduced pressure under 60~80 ℃ of temperature, vacuum-0.05~-0.06MPa condition, and being concentrated into proportion is 1.25~1.35 o'clock, must treat the American-cockroach-extract that digestive tract ulcer is used.
2. the extracting method of the American-cockroach-extract that treatment digestive tract ulcer according to claim 1 is used, it is characterized in that, described step C can be by the following technical solutions: step B gained coarse powder mixed liquor is carried out to reflux, extract, 4 times at the temperature of 75~80 ℃, when coarse powder mixed liquor is extracted for the first time, the ethanol that adds 5 times of amount concentration 92% of coarse powder, extraction time is 5 hours; Each ethanol that adds 4 times of amount concentration 92% of coarse powder that extracts for the second time, extraction time is 4 hours, merges four times extracting solution, filters to obtain ethanol extract.
3. the extracting method of the American-cockroach-extract that treatment digestive tract ulcer according to claim 1 and 2 is used, it is characterized in that, described step e can be by the following technical solutions: the purified water that step D gained ethanol concentrated solution is added to 8 times of amounts of ethanol concentrated solution weight, behind warming while stirring to 85~95 ℃, stir 40 minutes, mixing speed is 40 revs/min, and then insulation leaves standstill and within 4 hours, makes profit layering.
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Address after: 650217 Yunnan Province Economic and Technological Development Zone Kunming information industry base of Forest Road No. 160 Patentee after: Kunming cinorch pharmaceutical Limited by Share Ltd Address before: Kunming City, Yunnan province 650021 Dongfeng West Road No. 1 building 12 floor, Kunming Baida C Patentee before: Kunming Sinoway Natural Pharmaceuticals Co., Ltd. |