CN101816693B - Echinacea purpurea extract powder and preparation method and application thereof - Google Patents
Echinacea purpurea extract powder and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides echinacea purpurea extract powder and a preparation method and application thereof, which can solve the problems of large dosage, slow response, low bioavailability, easy moisture absorption and agglomeration and serious waste of medicament resources of the powder which is prepared by a traditional preparation method. The echinacea purpurea extract powder comprises echinacea purpurea extract and micro-powder silica gel serving as a carrier material. The preparation method comprises the steps of crushing the raw medicament material echinacea purpurea, extracting the material by a microwave method, recovering ethanol, performing concentration on the material under reduced pressure, adsorbing the micro-powder silica gel and drying, compounding and packaging the material. The echinacea purpurea extract powder has high dissolution rate and high dissolution capability of the effective ingredient, ensures convenient storage and use of the echinacea purpurea superfine powder by adding the micro-powder silica gel serving as a moisture remover, an anti-caking agent and a flow aid and has a good effect for enhancing the immune function; and the echinacea purpurea extract powder is used for animals of low immune function and improving the immunity effect of vaccine so as to cure various bacterial diseases and viral diseases by matching with other medicaments.
Description
Technical field
The invention belongs to natural medicinal formulations for animals field, specifically, relate to a kind of Echinacea extract powder and its production and application.
Background technology
The immunoprophylaxis function of animal body and the immune system of animal body directly affect the fertility performance of animal, safeguard the normal immunoprophylaxis function of animal body, are the prerequisites that makes animal reach the ordinary production level or bring into play potential best fertility performance.The progress of immunostimulant also is an immunobiology, the Chinese medicine immunopharmacology, microbiology, molecular biology, animal nutrition, animal are produced and are learned and the mutual process that promotes that merges of human health, are representing the development trend of drug development, in case aquaculture is no longer taken the remuneration that antibiotic existence brings into account as today, antibiotic will be replaced by novel form fully.The disease-resistant preparation of immunostimulant of Chinese medicine and natural drug extract particularly, become today of fashion in " back to nature " " green consumption ", make natural medicinal plants become the good selection of modern medical service health care in the nature of things, and the disease-resistant preparation of the immunostimulant of natural medicinal plants extract has than chemicals special advantages: regulate body's immunity, preventing disease theraping effect is remarkable; Toxic and side effects is little, can not develop immunity to drugs.
Genus echinacea (
EchinaceaMoenck.) for originating in a class feverfew in America, also claiming " SONGGUOJU ", is one of plant amedica the longest in the western history, also is world-famous " immunity " plant, has outstanding immunological enhancement and anti-infectious function.This platymiscium has 8 kinds and several mutation, and what wherein be developed as medicine is mainly three kinds of Echinacea (Echinacea purpurea Moench), Echinacea angustifolia (SONGGUOJU) and white SONGGUOJU.The main component of this platymiscium is caffeic acid derivant, alkylamide compound, polysaccharide and glycoprotein, quintessence oil, polyacetylene chemical compound, flavone compound, pyrrolizidine alkaloids etc., wherein caffeic acid derivant, alkylamide compound, polysaccharide and glycoprotein are the main components of its immunological enhancement, can activate the immunoreation of body, the specificity of enhancing body and non-specific immunity.For many years, China is with the success of this plant introduction, and result of study shows that introduce a fine variety Echinacea and compare with the original producton location Echinacea, significant change does not take place its main component, indicating that this plant can be used as a kind of new medicine resource of China.
Shortcomings such as traditional powder is medical material directly to be pulverized make for coarse powder, exists dosage big, and onset is slow, and bioavailability is low, and the drug resource waste is more serious, and there is poor stability in oral liquid, defectives such as transportation, preservation inconvenience.In addition, Echinacea is directly pulverized the easy moisture absorption caking of the powder of making, and is not easy to preserve and use.
Summary of the invention
The invention provides a kind of Echinacea extract powder and its production and application, it is big to solve the powder dosage that routine fashion makes, and onset is slow, and bioavailability is low, moisture absorption caking easily, the problem that the drug resource waste is more serious.
For solving the problems of the technologies described above, the present invention is achieved by the following technical solutions:
A kind of Echinacea extract powder comprises Echinacea extract and micropowder silica gel, and its percentage by weight prescription is Echinacea extract 10.0%-30.0%, micropowder silica gel 70.0%-90.0%, and described micropowder silica gel is a carrier material.
Further, every 1g Echinacea extract powder is made by 1-3g Echinacea medical material, and the chicoric acid weight percentage is 0.3%-3.0% in this Echinacea extract powder.
Again further, every 1g Echinacea extract powder contains Echinacea crude drug 2g, and the chicoric acid weight percentage is 0.4%-1.5% in this Echinacea extract powder.
Further, described Echinacea medical material is meant pale reddish brown Echinacea
Echinacea purpurea(L.) stem of Moench., leaf, flower.
A kind of preparation method of Echinacea extract powder comprises the steps:
(1) coarse pulverization: with the Echinacea pulverizing medicinal materials of plant pulverizer, cross the 60-80 mesh sieve, obtain the Echinacea coarse powder with water content≤12%;
(2) above-mentioned Echinacea coarse powder is placed the microwave extraction device, add the alcoholic solution of percentage by weight 50-80% according to the ratio of solid-liquid ratio (kg:L) 1:5-1:30, soaked microwave extraction 1-3 time, the condition of each microwave extraction 20-40 minute, microwave frequency: 2400-2500MHz, extract temperature: 40-80 ℃, extraction time: 1-20 minute, filter and collect filtrate and medicinal residues, filtrate recycling ethanol, concentrating under reduced pressure obtain Echinacea extract extractum;
(3) the alcoholic solution microwave of the medicinal residues usefulness 20-30% that filtration in the step (2) is obtained 1-3 time, solid-liquid ratio (Kg:L) 1:10-1:20, microwave frequency: 2400-2500MHz, extract temperature: 40-80 ℃, extraction time: 0.5-10 minute, filter, filtrate recycling ethanol obtains Echinacea extract extractum;
(4) extractum that step (2) and (3) are obtained mixes, add 2-5 doubly to the micropowder silica gel absorption of extractum weight, 50-60 ℃ of following constant temperature drying to water content less than 6%, get the Echinacea extract mixture, adding 0.5-3 then doubly is mixed to every 1g Echinacea extract powder to the micropowder silica gel of this extract mixtures and contains Echinacea crude drug 1-3g, quantitative weighing, pack, seal, promptly get Echinacea extract powder.
Above-mentioned solid-liquid ratio (kg:L) refers to Echinacea medicinal powder weight and the ratio that extracts solvent volume.
Further, the grinding particle size scope of Echinacea is 50-180 μ m in the step (1).
The application of Echinacea extract powder aspect preparation animal immunity potentiator and various bacillary, viral disease medicine.Echinacea extract powder is used for the immunologic hypofunction animal, also can be used for improving immune effect of vaccine, cooperates other drug to treat the application of various bacillary, viral disease aspects.
The reasonability of the inventive method is described below in conjunction with test method.
Echinacea coarse powder: the Echinacea pulverizing medicinal materials is crossed 80 mesh sieves, get Echinacea coarse powder (diameter of particle is less than 180 μ m);
Echinacea extract powder: get according to the described method preparation of foregoing invention content.
(1) mensuration of angle of repose
Take by weighing two kinds of each 50g of test specimen, place on the powder flowbility analyzer working sample angle of repose, parallel assay 3 duplicate samples, each sample is surveyed 3 times, averages.The results are shown in Figure 1;
Result of the test shows, different Echinacea extract powder differences are (p〉0.05) not significantly, is significantly higher than the angle of repose (p＜0.05) of Echinacea coarse powder, shows that the flowability of Echinacea extract powder is good than the Echinacea coarse powder that traditional handicraft makes.
(2) external dissolution rate is measured
Adopt " two XC three therapeutic methods of traditional Chinese medicine of Chinese pharmacopoeia version in 2005, dissolution medium is 15 minutes a distilled water (300ml) of the microwave degassing, temperature is 37 ± 0.5 ℃, rotating speed is 100rpm, and precision takes by weighing test specimen 3g and is spread in uniform on the medium liquid level, picks up counting when drug powder contact solution, respectively at 10,20,40 minutes sampling 5ml, press the note high effective liquid chromatography for measuring, calculate accumulation chicoric acid content in the dissolution medium, and calculate dissolution rate.
As seen from Figure 2, compare with common Echinacea powder, three detection time section, Echinacea extract powder amount of stripping chicoric acid in degassing distilled water is more, illustrates that the more traditional powder stripping of Echinacea extract powder is faster.
Chicoric acid content assaying method in the Echinacea powder
Chromatographic condition and system suitability test:
With octadecylsilane chemically bonded silica is filler: chromatographic column: ZORBAX Eclipse PlusC
18(4.6 * 250 μ m, 5 μ m); Mobile phase: methanol: 0.03% phosphoric acid (35:65); Flow velocity: 1.0ml/min; Column temperature: 35 ℃; Sample size: 10 μ l; Detect wavelength: 327nm.Theoretical cam curve is calculated by the chicoric acid peak should be not less than 3000.
The preparation of reference substance solution: it is an amount of that precision takes by weighing the chicoric acid reference substance, adds the solution that 70% methanol is made 0.128 mg/ml, promptly.
The preparation of need testing solution: precision is measured this product 1ml, puts in the 100ml volumetric flask, adds 30% methanol solution and is diluted to scale, shake up, and 0.45 μ m filtering with microporous membrane, promptly.
Assay method: accurate successively respectively chicoric acid reference substance each the 10 μ l of solution, serial reference substance solution and need testing solution just that draw, inject chromatograph of liquid, measure, promptly.Chicoric acid milligram number in the solution of content after in every 1ml concentrated solution standardize solution.
(3) hygroscopicity is measured
The glass exsiccator that the bottom is filled the sodium chloride supersaturated solution is put into 25 ℃ of baking oven constant temperature 5 h, and the interior relative humidity of exsiccator this moment is 75%.Put into the medicated powder of thick about 3 mm in the weighing botle bottom of constant weight, (the weighing bottle cap is opened) preserves in 25 ℃ calorstat in the exsiccator that is placed on the sodium chloride supersaturated solution of accurately weighing, timing sampling is weighed, parallelly do 3 parts, be calculated as follows the moisture absorption percentage rate, get average and the results are shown in Figure 3.
As seen from Figure 3, after the interpolation micropowder silica gel, the hydroscopicity of Echinacea extract powder obviously descends, and prevented from caking, and more traditional Echinacea powder is by remarkable advantages.
The using method of Echinacea extract powder is:
(1) prevent disease mixed feeding: every 100kg feedstuff, add Echinacea extract powder, chicken 100-300g; Pig 500-1500g, logotype 10 days.
(2) treatment disease mixed feeding: every 100kg feedstuff, add Echinacea extract powder, chicken 300-600g; Pig 2000-3000g, logotype 5 days.
Compared with prior art, advantage of the present invention and good effect are:
(1) Echinacea extract powder of the present invention is used 50-80% and 20-30% ethanol microwave extraction respectively, and extracts active ingredients is complete, and extraction time is short, and temperature is low, and the effective ingredient loss is few, the extraction efficiency height, and the medical material utilization rate is low, less wastage.
(2) the Echinacea extract powder of preparation method preparation of the present invention, the effective ingredient dissolution rate is fast, the dissolution rate height.
(3) add micropowder silica gel as hygroscopic agent, anticaking agents and fluidizer, be convenient to the preservation and the use of Echinacea superfine powder.
(4) the Echinacea extract powder raise immunity of the present invention's preparation is effective, is used for the immunologic hypofunction animal, also can be used for improving immune effect of vaccine, cooperates other drug to treat various bacillary, viral diseases.
Description of drawings
Fig. 1 be the Echinacea powder for preparing of various processes angle of repose measurement result relatively, analyze the Echinacea powder significant difference (p＜0.05) that the angle of repose of Echinacea extract powder and traditional handicraft prepare by statistics;
Fig. 2 be the Echinacea powder for preparing of various processes in the stripping situation of different time chicoric acid relatively, this shows that the stripping of Echinacea extract powder is fast than the Echinacea powder that traditional handicraft prepares;
Fig. 3 be the Echinacea powder for preparing of various processes the hydroscopicity measurement result relatively, this shows that the hydroscopicity of Echinacea extract powder is low than the Echinacea powder that traditional handicraft prepares.
The specific embodiment
The present invention is further detailed explanation below in conjunction with specific embodiment.
A kind of preparation method of Echinacea extract powder, step is as follows:
(1) China with water content≤12% introduces a fine variety Echinacea with the pulverizing of plant pulverizer, crosses 80 mesh sieves, obtains the Echinacea coarse powder;
(2) the Echinacea coarse powder that obtains in the step (1) is taken by weighing 1000g to the microwave extraction device, ratio according to solid-liquid ratio (Kg:L) 1:10 is added 70% alcoholic solution, soaked 30 minutes, microwave extraction 2 times, microwave frequency: 2400-2500MHz extracts temperature: 70 ℃, extraction time: 10 minutes, filter, filtrate recycling ethanol, concentrating under reduced pressure obtain Echinacea extract extractum;
(3) will filter the medicinal residues that obtain in the step (2) with 20% alcoholic solution microwave 2 times, solid-liquid ratio (Kg:L) 1:10, microwave frequency: 2400-2500MHz, extract temperature: 70 ℃, extraction time: 10 minutes, filter, filtrate recycling ethanol obtains Echinacea extract extractum;
(4) the extractum mixture that (2) and (3) are obtained adds 5 times to the micropowder silica gels of extractum mixture weight absorption, 50 ℃ of following constant temperature dryings to water content less than 6%, add an amount of micropowder silica gel and be mixed and made into 1000g Echinacea extract powder, quantitative weighing, pack, seal, promptly.
This product be lark to the taupe powder, percentage composition by weight, crude drug content is that every 1g powder contains Echinacea 1g.With the chicoric acid is index, detects through high performance liquid chromatography, and the chicoric acid content of this product is 0.65%.
(1) China with water content≤12% introduces a fine variety Echinacea with the pulverizing of plant pulverizer, crosses 80 mesh sieves, obtains the Echinacea coarse powder;
(2) the Echinacea coarse powder that obtains in the step (1) is taken by weighing 2000g to the microwave extraction device, ratio according to solid-liquid ratio (Kg:L) 1:8 is added 60% alcoholic solution, soaked 30 minutes, microwave extraction 2 times, microwave frequency: 2400-2500MHz extracts temperature: 80 ℃, extraction time: 15 minutes, filter, filtrate recycling ethanol, concentrating under reduced pressure obtain Echinacea extract extractum;
(3) the alcoholic solution microwave extraction of the medicinal residues usefulness 20-30% that filtration in the step (2) is obtained 2 times, solid-liquid ratio (Kg:L) 1:10, microwave frequency: 2400-2500MHz, extract temperature: 80 ℃, extraction time: 5 minutes, filter, filtrate recycling ethanol obtains Echinacea extract extractum;
(4) the extractum mixture that (2) and (3) are obtained adds 3 times to the micropowder silica gels of extractum mixture weight absorption, 50-60 ℃ of following constant temperature drying to water content less than 6%, add an amount of micropowder silica gel and be mixed and made into 1000g Echinacea extract powder, quantitative weighing, pack, seal, promptly.
This product be lark to the taupe powder, percentage composition by weight, crude drug content is that every 1g powder contains Echinacea 2g.With the chicoric acid is index, detects through high performance liquid chromatography, and the chicoric acid content of this product is 1.28%.
Embodiment 3
Grouping and processing
60 21 age in days wean three way cross piglets are divided into 3 groups at random.The Echinacea group is added 0.5% Echinacea extract powder in daily ration, the medicine matched group adds 0.02% colistine sulfate, the control group fed basal diet.Add back 7,14 and 28d and select 5 blood samplings for every group, side is decided peripheral blood lymphocyte activity of conversion and serum immune globulin and cytokine content.
Test method
From each group, selected 5 test pig at random on the 7th, 14 and 28 day respectively at test, the back vena cava anterior blood sampling 5ml that weighs on an empty stomach adds anticoagulant heparin, be used to do lymphocyte transformation test, the 10ml room temperature is placed, solidify the centrifugal 10min of back 3000rpm, separation of serum ,-20 ℃ of preservations, it is fixed to be used for immunoglobulin and cytokine content side.
The peripheral blood lymphocyte proliferation activity: with heparin anti-coagulating Hanks, 1 times of liquid dilution carefully adds to the lymphocyte separation medium upper strata, the centrifugal 20min of 2000rpmin, the cloud leukocytic cream is washed 2 times the centrifugal 15min of 1500rpm in the middle of drawing with serum-free RPMll640 nutritional solution.Behind the trypan blue dyeing counting viable count (more than 95%), transferring cell concentration with the RPMll640 culture fluid that contains 10% calf serum and convention amount two anti-(final concentration is 100U/ml) is 2.5 * 10
6Individual/ml.The lymphocyte suspension is added on people's 96 porocyte culture plates, every hole 90 μ l, each sample repeats 8 holes, and wherein 4 holes add people 10 μ l ConA (being mixed with the solution of 80 μ g/ml with RPMl l640 culture fluid) again, other 4 holes add people's equal-volume culture fluid, in 37 ℃, 5% CO
2Cultivate under the condition.After cultivating 44h, every hole adds people 20 μ l MTT (concentration 5mg/ml) respectively, continues to cultivate 4h.After cultivating end, every hole adds dimethyl sulfoxide 100 μ l, cell plates are placed extremely precipitation dissolving (about 5min) fully of concussion on the microwell plate agitator, on the enzyme linked immunological instrument, detect the light absorption value D at 570nm place, as the index of reflection LTA power.
Serum immune globulin content: use CX
4Type fully automatic blood biochemistry analyzer is measured IgG and IgM content by immunoturbidimetry, and test kit is Beijing Li Deman Biochem Technology, INC. product.
Serum cytokines content: adopt measured by radioimmunoassay.IL-2, IL-6 and TNF-α measure, and test kit is Beijing Ke Meidongya biotech company product, and concrete assay method strictness is undertaken by the test kit operating instruction.
Result of the test
The peripheral blood lymphocyte proliferation activity
By table 1 as seen, test 14d, 28d, the lymphocyte proliferation activity that the ConA of Echinacea group stimulates be significantly higher than the control drug group (
P＜0.05), the lymphocyte proliferation activity that stimulates of the non-ConA of 28d Echinacea group also be significantly higher than the control drug group (
P＜0.05), illustrates that adding ConA group lymphocyte proliferation activity is higher than and does not add the ConA group, illustrate that Echinacea has synergism to stimulation lymphopoiesis and ConA.
Table 1 Echinacea extract loose to the shadow noon of ablactational baby pig lymphocyte proliferation activity
Annotate: the different letter representation significant differences of going together (
P＜0.05).
Serum immune globulin and cytokine content
By table 2 as seen, tested the 7th day, Echinacea group serum il-2 and IL-6 content are significantly higher than matched group, and IL-2 content is significantly higher than but IL-6 and TNF content significantly are lower than the colistin group.Test 14d, Echinacea group blood serum IL-6 content significantly is lower than other two groups.Tested the 28th day, Echinacea group serum IgG and IgM content are significantly higher than other two groups.
Table 2 Echinacea is to the shadow noon of ablactational baby pig serum immune globulin and cytokine content
Above result of the test shows, adopts the Echinacea extract powder of the inventive method preparation to improve the reliable for effect of piglet immunological function.
The above only is preferred embodiment of the present invention, is not to be the restriction of the present invention being made other form, and any those skilled in the art may utilize the technology contents of above-mentioned announcement to be changed or be modified as the equivalent embodiment of equivalent variations.But every technical solution of the present invention content that do not break away to any simple modification, equivalent variations and remodeling that above embodiment did, still belongs to the protection domain of technical solution of the present invention according to technical spirit of the present invention.
Claims (4)
1. an Echinacea extract powder is characterized in that comprising Echinacea extract and micropowder silica gel, and its percentage by weight prescription is an Echinacea extract 10.0%-30.0%, and micropowder silica gel 70.0%-90.0%, described micropowder silica gel are carrier material;
Its preparation method comprises the steps:
(1) coarse pulverization: with the Echinacea pulverizing medicinal materials of plant pulverizer, cross 60-80 mesh sieves, obtain the Echinacea coarse powder with water content≤12%;
(2) above-mentioned Echinacea coarse powder is placed the microwave extraction device, add the alcoholic solution of percentage by weight 50-80% according to the ratio of solid-liquid ratio l:5-l:30, soaked microwave extraction 1-3 times, the condition of each microwave extraction 20-40 minutes, microwave frequency: 2400-2500MHz, extract temperature: 40-80 ℃, extraction time: 1-20 minutes, filter and collect filtrate and medicinal residues, filtrate recycling ethanol, concentrating under reduced pressure obtain Echinacea extract extractum;
(3) will filter the medicinal residues that obtain in the step (2) with 20-30% alcoholic solution microwave 1-3 times, solid-liquid ratio l:10-l:20, microwave frequency: 2400-2500MHz, extract temperature: 40-80 ℃, extraction time: 0.5-10 minutes, filter, filtrate recycling ethanol obtains Echinacea extract extractum;
(4) extractum that step (2) and (3) are obtained mixes, add the micropowder silica gel absorption of 2-5 times of extractum weight, 50-60 ℃ of following constant temperature dryings to water content less than 6%, get the Echinacea extract mixture, add 0.5-3 times of micropowder silica gels and be mixed to every lg Echinacea extract powder and contain Echinacea crude drug 1-3g, quantitative weighing, pack to this extract mixtures, seal, promptly get Echinacea extract powder;
Solid-liquid ratio in described step (2) and (3) is kg:L, refers to Echinacea medicinal powder weight and the ratio that extracts solvent volume.
2. according to the described Echinacea extract powder of claim l, it is characterized in that every lg Echinacea extract powder is made by 1-3g Echinacea medical material, and the chicoric acid weight percentage is 0.3%-3.0% in this Echinacea extract powder.
3. Echinacea extract powder according to claim 2 it is characterized in that every lg Echinacea extract powder contains Echinacea crude drug 2g, and the chicoric acid weight percentage is 0.4%-1.5% in this Echinacea extract powder.
4. according to claim 2 or 3 described Echinacea extract powders, it is characterized in that described Echinacea medical material is meant stem, leaf, the flower of pale reddish brown Echinacea Echinaceapurea (L.) Moench..
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| CN105663204A (en) * | 2014-11-19 | 2016-06-15 | 青岛加云华海健康科技有限公司 | Composition and preparation capable of improving immune function, resisting fatigue and treating cold as well as preparation method and application of composition |
| CN105982952B (en) * | 2015-03-02 | 2021-04-23 | 北京大北农动物保健科技有限责任公司 | A pharmaceutical composition, ZIGUANBAOGEN, comprises premix, concentrate and batch |
| CN106380402B (en) * | 2016-08-29 | 2018-09-21 | 珀莱雅化妆品股份有限公司 | A kind of preparation method for extracting high pure chicoric acid from Echinacea |
| CN115886126A (en) * | 2022-10-17 | 2023-04-04 | 青海大学 | Chicoric acid feed additive based on plateau environment, preparation method and application |
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| CN1587251A (en) * | 2004-07-20 | 2005-03-02 | 北京化工大学 | Process for preparing chicoric acid from echinacea purpurea |
| CN101032541A (en) * | 2006-07-28 | 2007-09-12 | 成都地奥九泓制药厂 | Echinacea purpurea extractive and the preparing method and the content measuring method |
| CN101199838A (en) * | 2007-12-21 | 2008-06-18 | 郭炳华 | Lactase powders and preparing method thereof |
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|---|---|---|---|---|
| CN1587251A (en) * | 2004-07-20 | 2005-03-02 | 北京化工大学 | Process for preparing chicoric acid from echinacea purpurea |
| CN101032541A (en) * | 2006-07-28 | 2007-09-12 | 成都地奥九泓制药厂 | Echinacea purpurea extractive and the preparing method and the content measuring method |
| CN101199838A (en) * | 2007-12-21 | 2008-06-18 | 郭炳华 | Lactase powders and preparing method thereof |
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| Mohammad Hudaib et al..Recovery evaluation of lipophilic markers from Echinacea purpurea roots applying microwave-assisted solvent extraction versus conventional methods.《J.Sep.Sci.》.2002,第26卷(第1-2期), * |
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Address after: 266061 Shandong city of Qingdao province high tech park of Laoshan district by the No. 29 Shandong Road, building 605 high speed Patentee after: Qingdao KDN Pharmaceutical Co., Ltd. Address before: 266061 Shandong city of Qingdao province high tech park of Laoshan district by the No. 29 Shandong Road, building 605 high speed Patentee before: Qingdao Continent Biotech Co., Ltd. |
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| C56 | Change in the name or address of the patentee |
Owner name: QINGDAO WEILAN BIOLOGY CO., LTD. Free format text: FORMER NAME: QINGDAO KDN PHARMACEUTICAL CO., LTD. |
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| CP03 | Change of name, title or address |
Address after: 266111 Shandong city of Qingdao province Chengyang Qingda Industrial Park, the first northbound dual Patentee after: QINGDAO VLAND BIOLOGICAL CO., LTD. Address before: 266061 Shandong city of Qingdao province high tech park of Laoshan district by the No. 29 Shandong Road, building 605 high speed Patentee before: Qingdao KDN Pharmaceutical Co., Ltd. |