CN103432283B - Application of physalis pubescens in preparation of medicaments or health care products for treating or preventing tumor and neurodegenerative diseases - Google Patents
Application of physalis pubescens in preparation of medicaments or health care products for treating or preventing tumor and neurodegenerative diseases Download PDFInfo
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Abstract
The invention discloses new application of physalis pubescens, i.e., application of the physalis pubescens in preparation of medicaments or health care products for treating or preventing tumor and neurodegenerative diseases. The invention also provides a preparation method of physalis pubescens fruit juice, flesh and seed extracts and persistent calyx extract. Research shows that an Nrf2 (Nuclear factor-erythroid 2-related factor 2) signal channel can be activated by the physalis pubescens fruit juice, the flesh and seed extracts and the persistent calyx extract to promote anti-oxidation and expression of II phase detoxifying enzyme, increase the level of glutathion in cells, enhance the reducing capacity in the cells, suppress the cell toxicity caused by cancerogen arsenic and weaken the neurotoxicity induced by active oxygen H2O2. Thus, the physalis pubescens can be prepared into corresponding oral preparations and injections and is used for preventing the tumor and neurodegenerative diseases.
Description
Technical field
The present invention relates to the novelty teabag of mushroom ma, particularly relate to the application of mushroom ma in preparation treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or health product.
Background technology
Along with the development of society, the improvement of human living standard and medical environment, human longevity obtains significant prolongation, but simultaneously, the sickness rate of malignant tumor, neurodegenerative diseases is also in raising, and serious threat human health, brings white elephant to country and society.There is no under active drug realizes the prerequisite of effectively treating above-mentioned disease, research and development have medicine and the health product of preventive effect, prevent the early origin of disease and become effective coping strategy.
Nuclear factor Nrf2(Nuclear factor-erythroid2-related factor2) be the important transcription factor regulating cell Redox balance, by with antioxidase and II phase detoxication enzyme promoter region Antioxidation reaction original paper (ARE) in conjunction with regulating cell redox equilibrium, its target gene comprises the II phase detoxication enzyme of coding GST, UGT, γ GCS, NQO1, and the endogenous anti-oxidative albumen such as GCL, HO-1.Under body is exposed to the material that electrophilicity foreign body, chemical carcinogen, endogenous oxidant etc. have damage body; Nrf2 just can be activated and pass through to raise antioxidase and II phase detoxication enzyme removing nuisance; protection body is from damage (the Lau et al. of poisonous substance; Pharmacol.Res.; 2008; 58,262-270).Therefore, by activating Nrf2 signal path, enhancing body self removes the ability of poisonous substance, can the generation of prevention of various diseases, such as tumor and neurodegenerative diseases.
Under oxidative stress status, in the face of endogenous and exogenous poisonous substance are to the infringement of body, exogenous Nrf2 agonist is utilized to raise body Nrf2 level, can enhancing body self-defense ability, the generation for prophylaxis of tumours, neurodegenerative diseases significant (Magesh etal., Med.Res.Rev., 2012,32,4,687-726).Activate Nrf2 signal path, II phase detoxication enzyme level can be raised, remove carcinogen or reduce its toxicity, suppress the DNA damage of carcinogen induction, gene mutation, thus the generation of prophylaxis of tumours.Expressing by raising Nrf2, can glutathione levels be increased, strengthen activities of antioxidant enzymes, active oxygen in scavenger cell, T suppression cell lipid peroxidation, reducing the sickness rate of the neurodegenerative diseases such as Alzheimer's disease and parkinson.Therefore, there are the monomeric compound of Nrf2 agonism, plant extract etc. can effectively prophylaxis of tumours and neurodegenerative diseases occur.
Mushroom ma is Solanaceae Physalis (Physalis) plant, is distributed in China northeast, North China, In Middle And Lower Reaches of Changjiang River widely.The Physalis pubescens L. of market sale be generally Calyx seu fructus physalis (Physalis alkekengil var.francheti (Mast.) Makino), Physalis pubescens L. (Physialis pubescensL.), fruitlet Calyx seu fructus physalis (Physialis peruviana) outer by the fruit of Constellation calyx.A large amount of oleic acid is contained in its fruit and Constellation calyx, the unsaturated fatty acids such as linoleic acid, abundant inorganic elements (higher with the content of potassium, phosphorus, sodium, magnesium and calcium), 18 seed amino acids and abundant vitamin (Agriculture of Anhui science, 2012,40,16113-16114).
Summary of the invention
For above-mentioned prior art, the invention provides the novelty teabag of mushroom ma---the application in preparation treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or health product.In addition, present invention also offers mushroom ma extract---the preparation method of Physalis pubescens L. juice, sarcocarp seed extract, Constellation calyx extract.
The present invention is achieved by the following technical solutions:
The present inventor is found by research; Physalis pubescens L. juice, sarcocarp seed extract, Constellation calyx extract can activate Nrf2 signal path; and the cytotoxicity that energy Cell protection opposing arsenic and hydrogen peroxide produce; therefore; can with mushroom ma for the health product of prophylaxis of tumours, neurodegenerative diseases be prepared by raw material; also can prepare treatment tumor, neurodegenerative diseases medicine (through By consulting literatures; activate the report of Nrf2 signal path up to now there are no mushroom ma, also have no the report of mushroom ma for tumor, neurodegenerative diseases prevention).
During embody rule, can with mushroom ma extracts such as Physalis pubescens L. juice, sarcocarp seed extract, Constellation calyx extracts for raw material, add medically acceptable adjuvant, make the dosage forms such as capsule (comprising soft capsule), tablet, powder, granule, oral liquid, medicated wine, pill, pellet, mixture, tincture, preferred particulates agent, capsule, tablet; Or mushroom ma will be carried get thing and be further purified and make ejection preparation.Also mushroom ma extract and other can be had tumor, neurodegenerative diseases and treat or the medicament mixed of preventive effect, add again or do not add medically acceptable adjuvant, making the dosage forms such as capsule (comprising soft capsule), tablet, powder, granule, oral liquid, medicated wine, pill, pellet, mixture, tincture, injection.
Described Physalis pubescens L. juice, prepares by the following method: separate real for Physalis pubescens L. with Constellation calyx, get fruit and squeeze the juice, filter, filtrate is Physalis pubescens L. juice, can add suitable quantity of water more according to demand, to be mixed with the fruit juice of variable concentrations.
Described Physalis pubescens L. meat seed extract, prepares by the following method:
Separate real for Physalis pubescens L. with Constellation calyx, get fruit and squeeze the juice, filter to obtain fruit juice, sarcocarp and seed; Get sarcocarp and seed, by 0 ~ 95% ethanol (referring to volume parts, being pure water when getting " 0 ") reflux, extract, 1 ~ 8 time, each solvent load is 1 ~ 20 times of medical material weight (sarcocarp and seed), and each extraction time is 0.5 ~ 10 hour; Merge extractive liquid, filters, and reclaims ethanol (as reclaim under reduced pressure), concentrates to obtain extractum; Add the water suspendible of extractum weight 1 ~ 20 times in extractum after, by the dichloromethane extraction of suspension volume 1 ~ 20 times, water phase separated and dichloromethane phase, dichloromethane is concentrated mutually, dry, obtain sarcocarp seed extract.
Described mushroom ma Constellation calyx extract, prepares by the following method:
Separate real for Physalis pubescens L. with Constellation calyx, get Constellation calyx, by 0 ~ 95% ethanol (referring to volume parts, being pure water when getting " 0 ") reflux, extract, 1 ~ 8 time, each solvent load is 1 ~ 20 times of Constellation calyx weight, and each extraction time is 0.5 ~ 10 hour; Merge extractive liquid, filters, and reclaims ethanol (as reclaim under reduced pressure), concentrated, dry, obtains mushroom ma Constellation calyx extract.
Described Physalis pubescens L. juice, Physalis pubescens L. meat seed extract, mushroom ma Constellation calyx extract, all may be used for preparing treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or health product.
The present inventor completes Physalis pubescens L. juice, sarcocarp and seed extract, Constellation calyx extract to the research of Nrf2 signal activation effect.Result shows, above-mentioned three kinds of mushroom ma extracts can activate Nrf2 at protein level, increases the expression of Nrf2 and downstream gene NQO1 and GCS thereof, strengthens cell reducing power by the level increasing glutathion inside cell.Inventor also finds to show the ability of T suppression cell canceration by the cytotoxicity that they can suppress carcinogen arsenic and induce; H can be reduced
2o
2inducing nerve cell toxicity, shows the potentiality of prevention of neurodegenerative diseases.Below for Physalis pubescens L. juice, introduce its effect to Nrf2 signal path:
Employing can the MDA-MB-231-Luc cell line of luciferase plasmids that relies on containing ARE of stably express, compare Physalis pubescens L. juice and other fruit (Fructus Fragariae Ananssae, Fructus Pruni pseudocerasi, the Fructus Lycopersici esculenti) effect to Nrf2, result shows that Physalis pubescens L. juice has the effect activating Nrf2 signal path, and its activity is better than other fruit (Fig. 1).The luciferase reporting screening test adopting ARE to rely on instructs as activity, flow process is extracted according to shown in Fig. 2, tracking activity has the real and Constellation calyx position of the Physalis pubescens L. of Nrf2 agonism, the effect (Fig. 3) that result shows Physalis pubescens L. fruit juice, sarcocarp seed extract dichloromethane position, Constellation calyx extract all have activation Nrf2 signal path.
Select human breast carcinoma MDA-MB-231 cell as detection cell, evaluate Physalis pubescens L. juice to the effect of Nrf2 signal path.Western blot shows, Physalis pubescens L. juice can raise the expression of Nrf2 albumen, and can promote the expression (Fig. 4) of downstream antioxidation and II phase detoxication enzyme albumen NQO1 and γ GCS.
Select people's normal lung epithelium HBE cell, have detected the impact of Physalis pubescens L. juice on glutathione levels.Result shows, and Physalis pubescens L. juice can increase glutathione levels (Fig. 5), strengthens reducing power and Scavenger of ROS ability in cell.
Select the cytotoxicity model of carcinogen arsenic induction, evaluate Physalis pubescens L. juice to the protective effect of people's normal lung epithelium HBE cell.After the process of Physalis pubescens L. juice, cells survival rate is significantly higher than non-agent-feeding treatment group, proves to show that Physalis pubescens L. juice can be used for the prevention of tumor by the cytotoxicity (Fig. 6) that Physalis pubescens L. juice can suppress trivalent arsenic and induces.Find, sarcocarp seed extract and Constellation calyx extract have the ability that the prophylaxis of tumours identical with Physalis pubescens L. juice is formed simultaneously.
Select active oxygen H
2o
2the cytotoxicity model of induction, evaluates Physalis pubescens L. juice to the protective effect of neurocyte PC12.Result shows that Physalis pubescens L. juice can suppress H
2o
2the toxicity produced, improves cells survival rate (Fig. 7).The many toxicity produced with active oxygen of the generation of neurodegenerative diseases is closely related, and this result proves that Physalis pubescens L. juice can be used for the prevention of neurodegenerative diseases.Sarcocarp seed extract has the ability of the prevention of neurodegenerative diseases identical with Physalis pubescens L. juice with Constellation calyx extract.
Accompanying drawing explanation
Fig. 1: the ARE luciferase reporting test relied on shows that Physalis pubescens L. juice can activate Nrf2 signal path, and the implication that 1:500,1:100,1:50 in figure represent is the extension rate of fruit juice.
Fig. 2: Physalis pubescens L. reality and Constellation calyx branch extract flow chart.
Fig. 3: the ARE luciferase reporter test determination mushroom ma each several part relied on activates the effect of Nrf2 signal path.
Fig. 4: western blot analysis shows that Physalis pubescens L. juice can activate its downstream gene of Nrf2 at protein level, and the implication that 1:500,1:100,1:50 in figure represent is the extension rate of fruit juice.
Fig. 5: Physalis pubescens L. juice can increase glutathione levels, the implication that 1:500,1:100,1:50 in figure represent is the extension rate of fruit juice.
Fig. 6: Physalis pubescens L. juice can reduce the cytotoxicity (* p<0.05) of arsenic induction.
Fig. 7: Physalis pubescens L. juice can reduce H
2o
2the cytotoxicity (* p<0.05) of induction.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further illustrated, and following embodiment is only the object of explanation, not for limiting the present invention.
Embodiment 1: Physalis pubescens L. juice is to the activation of Nrf2 signal path
Method: the preparation of (1) Physalis pubescens L. juice
Physalis pubescens L. 200g, separates fruit and Constellation calyx, gets fruit and squeezes the juice, filter, obtain filtrate 130mL, be Physalis pubescens L. juice.Fructus Fragariae Ananssae, Fructus Pruni pseudocerasi, Fructus Lycopersici esculenti adopt same procedure to prepare fruit juice, for activity rating.
(2) cultivation of human breast cancer cell MDA-MB-231 cell line
Human breast cancer cell MDA-MB-231 purchased from American Type culture collection warehousing (ATCC), adopts the MEM culture medium containing 10% hyclone (FBS), 2mMHEPES and 6ng/mL insulin, is placed in 37 DEG C, 5%CO
2cultivate in incubator.
(3) luciferase reporting that ARE relies on is tested
MDA-MB-231-Luc cell is inoculated on 96 orifice plates, the testing compound of variable concentrations is added after 24 hours, process 16 hours, adopt cell pyrolysis liquid [0.1M potassium phosphate and 1mM dithiothreitol, DTT] cell lysis, with detection liquid (25mM glycylglycine, 15mM magnesium sulfate, 500 μMs of ATP, 250 μMs of fluoresceins and 250 μMs of coenzyme As), measure fluorescence intensity.
Result: as shown in Figure 1, Physalis pubescens L. juice significantly can strengthen the uciferase activity that ARE relies on, and 1:50 concentration process groups of cells, its intensity is 4 times of blank group, is 1.5 times of positive control medicine sulforaphen (2.5 μMs).Under mensuration concentration (1:50-1:500), Fructus Fragariae Ananssae, Fructus Pruni pseudocerasi, tomato fruit juice do not show obvious Nrf2 activation.The above results shows, compared with Fructus Fragariae Ananssae, Fructus Pruni pseudocerasi, tomato fruit juice, Physalis pubescens L. juice can better induce Nrf2 signal path, has better protective effect to body.
Embodiment 2: the different preparation at mushroom ma position and the effect to Nrf2 signal path thereof
Method: the preparation (branch extracts flow chart as shown in Figure 2) at (1) different mushroom ma position
Physalis pubescens L. 200g, separates fruit and Constellation calyx, gets fruit and squeezes the juice, and filters, obtains 130mL filtrate (Physalis pubescens L. juice) and 50g filtering residue (sarcocarp and seed); Sarcocarp and seed 50g, with 75% alcohol reflux 2 times of its weight 10 times, each 1 hour, merge extractive liquid, filters, is concentrated into extractum, add water 100mL suspendible, and with dichloromethane extraction (2 × 100mL), evaporate to dryness dichloromethane obtains sarcocarp seed extract 1.1g mutually; Constellation calyx 6g, with 75% alcohol reflux 2 times of its weight 10 times, each 1 hour, merge extractive liquid, filtered, is concentrated into Constellation calyx extract 1.2g.
(2) luciferase reporting that ARE relies on is tested
Method as described in Example 1.
Result: as shown in Figure 3, the sarcocarp seed extract prepared according to the method described above and Constellation calyx extract can strengthen the uciferase activity that ARE relies on, and show that these two kinds of extracts have the effect activating Nrf2 signal path.
Embodiment 3: Physalis pubescens L. juice can raise Nrf2 and with the expression of downstream genes protein level
Method: western blot analysis (Western blot) detects the change of protein level in cell
MDA-MB-231 cell is inoculated in diameter 35mm culture dish, be cultured to after density reaches 70% ~ 80%, add Physalis pubescens L. juice (Physalis pubescens L. juice is prepared by embodiment 1) the process 16h of variable concentrations, PBS washs 2 times, adds cell pyrolysis liquid (50 μ g/ml aprotiniies, 0.5mM Phenylmethanesulfonyl fluoride, 1mM sodium vanadate, 10mM sodium fluoride, 10mM β-phosphoglycerol), collect albumen and adopt Bradford method to measure protein concentration.Each sample thief albumen (100 μ g) loading, SDS-PAGE protein isolate component also adopts electrotransfer method to be transferred on cellulose nitrate film by protein band.Thin film through TBS preparation 5% skim milk powder solution room temperature close 1h after, respectively with each testing protein antibody 4 DEG C of overnight incubation.Add respectively after TBS washing horseradish peroxidase two anti-hatch 1h after, carry out analysis of protein with enhancement mode ECL chemiluminescence.
Result: as shown in Figure 4, cell is after Physalis pubescens L. juice process 16h, and Nrf2 and downstream antioxidation thereof and II phase detoxication enzyme albumen NQO1 and γ GCS protein level present dose dependent to be increased, and confirms that Physalis pubescens L. juice can plan Nrf2 signal path on protein level.
Embodiment 4: Physalis pubescens L. juice increases glutathione levels
Method: the cultivation of (1) people's normal lung epithelial cell HBE cell
People's normal lung epithelial cell HBE purchased from American Type culture collection warehousing (ATCC), adopts MEM culture medium, and adds 10% hyclone (FBS) wherein, 5% glutamine, be placed in 37 DEG C, 5%CO
2cultivate in incubator.
(2) mensuration of glutathion inside cell content
HBE cell is inoculated in diameter 35mm culture dish, be cultured to after density reaches 70% ~ 80%, the Physalis pubescens L. juice (Physalis pubescens L. juice is prepared by embodiment 1) adding variable concentrations processes 24 hours, PBS washs 2 times, adds 0.5mL50mM sodium phosphate and 1mMEDTA buffer receipts cell, ultrasonic 1min, centrifugal 15 minutes of 10000g, get supernatant, measure the operation of test kit description according to glutathion, 412nm measures absorbance and calculates glutathione content.
Result: as shown in Figure 5, Physalis pubescens L. juice significantly can increase glutathione levels, strengthens reducing power in cell.
Embodiment 5: Physalis pubescens L. juice can suppress trivalent arsenic to the toxicity of people's pulmonary branches tracheal epithelium HBE cell
Method: mtt assay measures the Cytotoxic protective effect that compound is induced arsenic
HBE cell is inoculated on 96 orifice plates, add variable concentrations testing compound process 16 hours, then the arsenic and the strength juices to be measured (Physalis pubescens L. juice is prepared by embodiment 1) that add variable concentrations process 24 hours, and after adding MTT3 hour, 590nm measures absorbance and also calculates cells survival rate.
Result: as shown in Figure 6; adopt 1:100 concentration Physalis pubescens L. juice pretreatment cell 16 hours; then add the arsenic of 20 μMs, 40 μMs and 1:100 concentration Physalis pubescens L. juice process cell 24 hours, result shows that Physalis pubescens L. juice has protective effect to HBE cell, can suppress the cytotoxicity that arsenic is induced.The cells survival rate of fruit juice processed group is apparently higher than not adding medicine processed group.Result proves, the toxicity that Physalis pubescens L. juice can suppress carcinogen arsenic to be induced, and can be used in the prevention and therapy of tumor.
Embodiment 6: Physalis pubescens L. juice can suppress H
2o
2to the toxicity of neurocyte strain PC12
Method: the cultivation of (1) neurocyte PC12
Neurocyte strain PC12 purchased from American Type culture collection warehousing (ATCC) adopts the DMEM culture medium containing 15% hyclone (FBS), 100U/ml penicillin and 100U/ml streptomycin, is placed in 37 DEG C, 5%CO
2cultivate in incubator.
(2) mtt assay measures compound to H
2o
2the Cytotoxic protective effect of induction
PC12 cell is inoculated on 96 orifice plates, add variable concentrations Physalis pubescens L. juice to be measured (Physalis pubescens L. juice is prepared by embodiment 1) process 16 hours, then add the arsenic of variable concentrations and Physalis pubescens L. juice to be measured process 24 hours, after adding MTT3 hour, 590nm measures absorbance and also calculates cells survival rate.
Result: shown in Fig. 7, adopts 1:100 concentration Physalis pubescens L. juice pretreatment cell 16 hours, then adds the H of 100 μMs, 200 μMs
2o
2with 1:100 concentration Physalis pubescens L. juice process cell 24 hours, result showed that Physalis pubescens L. juice has protective effect to PC12 cell, can suppress H
2o
2the cytotoxicity of induction.The cells survival rate of Physalis pubescens L. juice processed group is apparently higher than not adding medicine processed group.Result proves, Physalis pubescens L. juice can inhibit activities oxygen H
2o
2the neurotoxicity produced, can be used in the prevention and therapy of neurodegenerative diseases.
Embodiment 7: the preparation of Physalis pubescens L. meat seed extract
Physalis pubescens L. 5kg, fruit separates with Constellation calyx, is squeezed the juice by fruit, filter, obtain 1.25kg filtering residue (sarcocarp and seed), with 75% alcohol reflux 2 times of its weight 10 times, each 1 hour, merge extractive liquid, filters, is concentrated into extractum, add water 1000mL suspendible, and with dichloromethane extraction (2 × 1000mL), evaporate to dryness dichloromethane obtains sarcocarp seed extract 25g mutually, and yield is 0.5%.
Embodiment 8: the preparation of mushroom ma Constellation calyx extract
Physalis pubescens L. 5kg, separates fruit and Constellation calyx, obtains Constellation calyx 150g, and with 75% alcohol reflux 2 times of its weight 10 times, each 1 hour, merge extractive liquid, filtered, be concentrated into extractum, obtain Constellation calyx extract 30g, yield 0.6%.
Embodiment 9: the preparation of tablet
Mushroom ma Constellation calyx extract (prepared by embodiment 8) 20g, add corn starch 30g, dextrin 15g, fully mixes, granule processed, and dry, granulate, adds appropriate Pulvis Talci, tabletting, to obtain final product.
Embodiment 10: the preparation of capsule
Mushroom ma Constellation calyx extract (prepared by embodiment 8) 20g, add starch 20g, dextrin 15g, microcrystalline Cellulose 8g, fully mixes, granule processed, and dry, granulate, adds appropriate magnesium stearate, encapsulated, to obtain final product.
Claims (5)
1. a Physalis pubescens L. meat seed extract, is characterized in that: prepare by the following method: separate real for Physalis pubescens L. with Constellation calyx, get fruit and squeeze the juice, filter to obtain fruit juice, sarcocarp and seed; Get sarcocarp and seed, with 0 ~ 95% alcohol reflux 1 ~ 8 time, each solvent load is 1 ~ 20 times of medical material weight, and each extraction time is 0.5 ~ 10 hour; Merge extractive liquid, filters, and reclaims ethanol, concentrates to obtain extractum; Add the water suspendible of extractum weight 1 ~ 20 times in extractum after, by the dichloromethane extraction of suspension volume 1 ~ 20 times, water phase separated and dichloromethane phase, dichloromethane is concentrated mutually, dry, obtain sarcocarp seed extract.
2. the application of Physalis pubescens L. meat seed extract according to claim 1 in preparation treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or health product.
3. a mushroom ma Constellation calyx extract, it is characterized in that: prepare by the following method: separate real for Physalis pubescens L. with Constellation calyx, get Constellation calyx, with 0 ~ 95% alcohol reflux 1 ~ 8 time, each solvent load is 1 ~ 20 times of Constellation calyx weight, and each extraction time is 0.5 ~ 10 hour; Merge extractive liquid, filters, and reclaims ethanol, concentrated, dry, obtains mushroom ma Constellation calyx extract.
4. the application of mushroom ma Constellation calyx extract according to claim 3 in preparation treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or health product.
5. the application according to Claims 2 or 3, it is characterized in that: during embody rule, with Physalis pubescens L. meat seed extract or/and Constellation calyx extract is for raw material, add medically acceptable adjuvant, make capsule, tablet, powder, granule, oral liquid, medicated wine, pill, pellet, mixture or tincture; Or by Physalis pubescens L. meat seed extract or/and Constellation calyx extract purification makes ejection preparation; Or: by Physalis pubescens L. meat seed extract or/and Constellation calyx extract and other have tumor, neurodegenerative diseases and treat or the medicament mixed of preventive effect, add again or do not add medically acceptable adjuvant, making capsule, tablet, powder, granule, oral liquid, medicated wine, pill, pellet, mixture, tincture or injection.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1271545A (en) * | 1999-04-26 | 2000-11-01 | 汪金江 | Physalis alkekengi beverage |
| CN101036509A (en) * | 2007-04-05 | 2007-09-19 | 王长山 | Physalis alkekengi can |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1271545A (en) * | 1999-04-26 | 2000-11-01 | 汪金江 | Physalis alkekengi beverage |
| CN101036509A (en) * | 2007-04-05 | 2007-09-19 | 王长山 | Physalis alkekengi can |
Non-Patent Citations (1)
| Title |
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| 山菇娘果汁饮料生产工艺的试验研究;于海杰，等;《科技信息》;20110330(第3期);3-4 * |
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Effective date of registration: 20190606 Address after: 276002 Bancheng Town, Lanshan District, Linyi City, Shandong Province Patentee after: Linyi Shansong Pharmaceutical Co. Ltd. Address before: 250061 culture West Road, Lishi District, Ji'nan, Shandong Province, No. 44 Patentee before: Shandong University |
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| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190711 Address after: 276002 Jinluo Science Park, Bancheng Town, Lanshan District, Linyi City, Shandong Province Co-patentee after: Linyi Shansong Pharmaceutical Co. Ltd. Patentee after: Linyi Jinluo Health Science and Technology Research Institute Address before: 276002 Bancheng Town, Lanshan District, Linyi City, Shandong Province Patentee before: Linyi Shansong Pharmaceutical Co. Ltd. |