CN106668077A - Marine bioactive composition and pharmaceutical preparation - Google Patents
Marine bioactive composition and pharmaceutical preparation Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/60—Fish, e.g. seahorses; Fish eggs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/616—Echinodermata, e.g. starfish, sea cucumbers or sea urchins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/655—Aquatic animals other than those covered by groups A61K35/57 - A61K35/65
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/04—Rhodophycota or rhodophyta (red algae), e.g. Porphyra
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Abstract
The invention provides a marine bioactive composition and a pharmaceutical preparation. The marine bioactive composition is prepared from the following components in parts by weight: 10 to 30 parts of oyster extract, 2 to 6 parts of kelp extract, 4 to 8 parts of seaweed extract, 5 to 10 parts of gloiopeltis furcata extract, 10 to 16 parts of hippocampus enzymolysis extract, 10 to 16 parts of sea cucumber extract, 4 to 8 parts of marine sponge extract, 2 to 6 parts of shark extract, and 15 to 25 parts of marine actinomycete fermentation liquor. The pharmaceutical preparation is a capsule, granules, an oral solution, a pill or medicinal granules prepared through mixing the composition, a pharmaceutical carrier and an additive. The composition has high pertinency, a good curative effect, little toxic or side effect, and a good antitumous effect.
Description
Technical field
The invention belongs to field of marine biotechnology, and in particular to a kind of activity combination of marine life and pharmaceutical formulation.
Background technology
Since the sixties in 20th century, people have carried out worldwide broad scale research to huge living marine resources,
Marine drug research and development upsurge is started.Wherein, anti-tumor active substance is especially noticeable, has become the whole world universal
The study hotspot of concern.Scholar foretells that most promising cancer therapy drug will be always from ocean, Marine Antitumor Active Products
The emphasis of marine drug research.
Tumor (tumour) refers to body under the effect of the various tumorigenesis factors, the new life that local organization hyperplasia is formed
Thing (neogrowth), because this neoplasm being in occupancy block-like protrusions, also referred to as vegetation (neoplasm) more.According to new life
The cell characteristics of thing and the hazardness degree to body, and tumor is divided into into benign tumor and the big class of malignant tumor two, and cancer
The as general name of malignant tumor.It should be noted that cancer and cancer are two different concepts, cancer refers to epithelial pernicious swollen
Tumor, is such as referred to as colorectal mucosa epithelial cancer, abbreviation colorectal cancer by the epitheliogenic malignant tumor of colorectal mucosa.Formed by skin epidermis
Title skin epidermis cancer, abbreviation skin carcinoma etc..If what doctor said so-and-so's trouble is cancer, that is, show patient's length is pernicious swollen
Tumor；If say that so-and-so suffers from is gastric cancer, the cancer that the gastric epithelial of patient is formed is meant, if say that patient obtains is stomach meat
Tumor, then show that this malignant tumor is not formed by mucosal epithelial cells, may be caused by smooth muscle cell canceration, or
Belong to malignant lymphoma of stomach etc..
Concha Ostreae, also known as oyster, oyster etc., is a kind of common seashells animal, belongs to Mollusca, lamellibranchiata
(Lamellibranchia), Ostreidae (Ostreidae), Concha Ostreae category.Concha Ostreae is Fresh ＆ Tender in Texture, nutritious, is a kind of nutriture value
The high food of value.Modern study shows, containing abundant glycogen, protein, aminoacid, needed by human micro in Carnis ostreae
Element, vitamin and the more unsaturated fatty acid with important physiologically active.It was verified that Concha Ostreae extract can be treated
Various diseases, play special curative effect.Currently, it is external in addition to Concha Ostreae is directly eaten as seafood, also develop big
Food of the amount with Concha Ostreae extract as main component, health product and medicine, these products not only have suitable nutrition or treatment
Value, and with high economic and social benefit.It is many about the preparation method of Concha Ostreae extract at present, such as
US66732 discloses a kind of method for preparing Concha Ostreae extract by Concha Ostreae juice；CN1024074C discloses a kind of full nutrition
The production method of oyster powder；CN1067553C discloses a kind of method by new fresh and alive Concha Ostreae effective component extracting；
CN1132646A prepares Concha Ostreae composition using enzymolysis process；CN1486634A also discloses that a kind of Concha Ostreae extract and its preparation side
Method.
Thallus Laminariae (Thallus Eckloniae) (Laminaria japonica) is extremely enriched in China's yield, and its medical value exists《Compendium of Materia Medica》、《God
Agriculture book on Chinese herbal medicine Jing》With《Food book on Chinese herbal medicine》Deng all having been described in traditional medical book.Modern scientific research proves that Thallus Laminariae (Thallus Eckloniae) has many
Health care, such as blood fat reducing, blood sugar lowering, antithrombotic, antitumor, radioprotective.Various biological functions of Thallus Laminariae (Thallus Eckloniae) are mostly and Thallus Laminariae (Thallus Eckloniae)
In physiologically active polysaccharide it is relevant.At present, crude polysaccharides are mainly first extracted in the extraction of laminarin, are then further separated pure
Change, then carry out Activity determination.This method uncertain factor is more, and active component loss is easily caused in separation process,
And detached laminarin is extracted not necessarily with antioxidation or anti-tumor activity.Chinese patent CN201210017025.3 is provided
It is a kind of while laminarin and its extraction separation method with antioxidation and anti-tumor activity, tests prove that, it is resulting
Laminarin there is more preferable antioxidation and anti-tumor activity, provide new selection to prepare antioxidation or antitumor drug.
Hippocampus use as Chinese crude drug and are had a long history in China, and beam is for TAO Hong-Jing《Collective Notes to Canon of Materia Medica》In to sea
Horse has been described that " its sweet in the mouth warm in nature, returns liver and kidney channel, with warming the kidney to invigorate YANG, the effects such as dispersing swelling and dissipating binds, married woman expedite the emergence of, can cure
Claim during the disease diseases such as respiratory system imbalance, sexual dysfunction, insomnia, asthenia, laryngopharynx swelling and pain, dermatosiss and difficult labour " " water horse ".
In recent years, marine actinomycete is increasingly becoming the important source of drug development, because it lives in high salt, high pressure, low
In the special environment of gentle low nutrition, many unique structures, the compound of effect novelty can be produced, cannot with land microorganism
The advantage of analogy.The quantity that new reactive compound is separated to from marine actinomycete increases year by year, includes many activity very high
Cytotoxic compound, wherein thiocoraline, salinosporamideA and ECO-4601 come into clinical research.Cause
This, marine actinomycete has caused extensive concern as a kind of new sources of cytotoxic compound.
Shark belongs to Chondrichthyess (Chondrichthyes), shark shape catalogue (Selachomorpha), kind about more than 250.
Shark is seldom to suffer from one of animal of malignant tumor in nature, and its sickness rate is hundred a ten thousandths.American scientist once did
Such research, the strong carcinogen aflatoxin B1 of high dose is expelled in shark body, it is impossible to induce cancer.
However, having no Concha Ostreae extract, Thallus Laminariae (Thallus Eckloniae) extract, Sargassum extract, gloiopeltis extract, Hippocampus enzymolysis and extraction at present
The report of thing, Stichopus japonicus extract, sponge extract, cartilage derived extract and ocean actinomycete fermentation liquid use in conjunction.
The content of the invention
The present invention proposes a kind of activity combination of marine life, and said composition has with strong points, good effect, toxic and side effects
Little, antitumous effect is good.
The technical scheme is that what is be achieved in that：
A kind of activity combination of marine life, is extracted by 10~30 parts of Concha Ostreae extract, 2~6 parts of Thallus Laminariae (Thallus Eckloniae) extract, Sargassum
4~8 parts of thing, 5~10 parts of gloiopeltis extract, 10~16 parts of Hippocampus enzymatic hydrolyzed extract, 10~16 parts of Stichopus japonicus extract, sponge are extracted
4~8 parts of thing, 2~6 parts of cartilage derived extract are constituted for 15~25 parts with ocean actinomycete fermentation liquid.
Preferably, in some embodiments of the present invention, Thallus Laminariae (Thallus Eckloniae) extract is fucoidan.
Preferably, in some embodiments of the present invention, marine actinomycete is marine actinomycete AFN1007, from China
Patent 200810123930.0.
Preferably, in some embodiments of the present invention, Sargassum extract is Sargassum polysaccharides, gloiopeltis extract is carried for methanol
Thing is taken, cartilage derived extract is the extract of shark liver and cartilage.
It is a further object to provide a kind of pharmaceutical formulation of activity combination of marine life, by combinations of the above
Thing is mixed and made into capsule, granule, oral liquid, pill or electuary with pharmaceutical carrier, additive.
Concha Ostreae extract of the present invention is prepared using known disclosed method, such as Chinese patent (ZL94101124.0)
It is prepared by the preparation method of disclosed Concha Ostreae extract and its preparation：
(1) fresh and alive Concha Ostreae is shelled, and washes roguing；
(2) in 1~5Kgf/cm3Water extraction is used at a temperature of the pressure (gauge pressure) of (kilogram) and 40~110 DEG C, is extracted time
Number is 1~3 time, and preferably 2 times, 0.5~2 hour every time, water used was deionized water, and Carnis ostreae is 1 with the weight ratio of water:1~
3, preferably 1:2.
(3) filter, remove residue；
(4) concentrating under reduced pressure in a vacuum；
(5) it is spray-dried in spray dryer, is obtained final product the Concha Ostreae extract of the present invention.
Laminarin is the main component in Thallus Laminariae (Thallus Eckloniae), has found in Thallus Laminariae (Thallus Eckloniae) there is 3 kinds of main polysaccharides, i.e. Algin so far
(algin), fucoidan (fucoidan) and laminarin (lami naran).Heretofore described Thallus Laminariae (Thallus Eckloniae) extract is at least wrapped
Containing fucoidan.
Hippocampus enzymatic hydrolyzed extract method therefor of the present invention is prepared using known disclosed method, such as Chinese patent
It is 100 by mass ratio 201510067879.6 disclosing a kind of Hippocampus trypsin digestion liquid:5 Hippocampus powder and trypsin
In being placed in beaker, and the PBS buffer solution of pH=8.0 is added to obtain mixed solution in beaker, and Hippocampus powder is buffered with PBS
The mass volume ratio of solution is 1:200, by mixed solution, water bath with thermostatic control digests 6~8h under conditions of 50~60 DEG C, then will
Mixed solution water-bath at least 10min under conditions of 100 DEG C, carries out centrifugal treating and takes supernatant to mixed solution afterwards, will
The membrane filtration that 0.45 μm of supernatant Jing, it (is Hippocampus enzymolysis and extraction that the liquid after filter is Hippocampus trypsin digestion liquid
Thing).
Gloiopeltis (Gloiopeltis furcata), Rhodophyta Endocladiaceae Gloiopeltis is annual red algae.Will in China
Gloiopeltis is used as edible and medicinal and for the existing long history of textile industry.Gloiopeltis is thin to human mouth tumor KB cell and HT229
Born of the same parents have selective inhibitory activity.
The skeletal system of shark is the cartilage for lacking blood vessel, accounts for the 6%~8% of its body weight.Shark cartilage is a kind of acid
Ateroid, containing compositions such as protein, glycosaminoglycan, chondroitin sulfate.Its antineoplastic component is mainly polysaccharide and one
A little activated protein factors.Anti-tumor active substance in shark liver is mainly Squalene, and Squalene is a kind of antitumor and control
Treat the bioactive substance of cardiovascular diseasess.Can be formed by acetate in vivo, participate in the biosynthesiss of cholesterol, promote biological oxygen
Change and body metabolism, while or terpenoid and other steroids important as precursors.
Beneficial effects of the present invention：
1st, the present invention in Concha Ostreae extract, Thallus Laminariae (Thallus Eckloniae) extract, Sargassum extract, gloiopeltis extract, Hippocampus enzymatic hydrolyzed extract,
Stichopus japonicus extract, sponge extract, cartilage derived extract and ocean actinomycete fermentation liquid are carried out after compatibility, can significantly activate NK
The activity of cell.NK cells can automatic identification and dissolving kinds of tumors or infected cell rapidly.Therefore, it can effectively be killed
Cancerous cell simultaneously prevents the transfer and diffusion of tumor, moreover, due to NK cells can automatic identification act on cancerous cell, it need not resist
Body or in advance and cytosiies, without the identification for relying on major histocompatibility complex.Thus, human normal cell is not had
There are any toxic and side effects.
2nd, Thallus Laminariae (Thallus Eckloniae) extract individually carries out anti-tumor experiment and finds that in fact its anti-tumor capacity is very weak, particularly comes into
The cell of cancer mid-term is more without any effect.But, inventor is had found Concha Ostreae extract, Thallus Laminariae (Thallus Eckloniae) extract, marine actinomycete
After fermentation liquid mixes with Hippocampus enzymatic hydrolyzed extract according to cooperation, can effectively suppress the growth of cancer medium cell, hepatoma carcinoma cell
The growth inhibition ratio of QGY7703 has reached 85%.Face on this basis, then use cooperatively with remaining components, more can promote by
The kill of cancer cell.
Specific embodiment
Embodiment 1
A kind of activity combination of marine life, by 20 parts of Concha Ostreae extract, 4 parts of fucoidan, 6 parts of Sargassum polysaccharides, gloiopeltis
8 parts of extract, 12 parts of Hippocampus enzymatic hydrolyzed extract, 12 parts of Stichopus japonicus extract, 5 parts of sponge extract, 3 parts and 20 parts of cartilage derived extract
Ocean actinomycete fermentation liquid AFN1007 is constituted.
Embodiment 2
A kind of activity combination of marine life, by 10 parts of Concha Ostreae extract, 6 parts of fucoidan, 4 parts of Sargassum polysaccharides, gloiopeltis
10 parts of extract, 10 parts of Hippocampus enzymatic hydrolyzed extract, 16 parts of Stichopus japonicus extract, 8 parts of sponge extract, 2 parts of cartilage derived extract and sea
15 parts of compositions of foreign actinomycetes fermentation liquor.
Embodiment 3
A kind of activity combination of marine life, by 30 parts of Concha Ostreae extract, 2 parts of fucoidan, 8 parts of Sargassum polysaccharides, gloiopeltis
5 parts of extract, 16 parts of Hippocampus enzymatic hydrolyzed extract, 10 parts of Stichopus japonicus extract, 4 parts of sponge extract, 6 parts of cartilage derived extract and ocean
25 parts of compositions of actinomycetes fermentation liquor.
Embodiment 4
This research according to Ministry of Public Health new drug approval pertinent regulations, to the present invention activity combination of marine life carried out it is right
The inhibitory action test of mice lung cancer model.Experiment is divided into 5 groups of embodiment 1~3, matched group, positive controls.
1st, test medicine：
The activity combination of marine life of embodiment 1~3, is configured to before use aqueous suspension.
2nd, animal
2.1 source：C57 mices, are provided, quality certification number by laboratory animal breeding factory of the Chinese Academy of Medical Sciences：The dynamic word of doctor the
01-3004。
2.2 body weight：18~20 grams.
2.3 sex：Male and female half and half.
2.4 each group number of animals：10 per group.
2.5 rearing conditions：Feedstuff is provided by animal reproduction factory of the Chinese Academy of Medical Sciences, animal sub-cage rearing, per 5, cage,
Male and female separate.At 20~26 DEG C, humidity is 40~60% to the control of animal indoor temperature.
3rd, experimental technique：
The foundation of 3.1 tumor models：Lotus knurl (Lewis lung cancer) mice is introduced from Beijing institute of materia medica, its tumor group is taken
Knit, single cell suspension is made in homogenate, it is 5 × 10 to count tumor cell6/ ml, the right under-arm of every mice is inoculated with 0.2ml.
3.2 experiment packet：Experiment takes transplanted tumor mice and is grouped at random, is divided into 5 groups, per group of 10 male and female half and half, respectively
Matched group (lotus knurl control), positive controls (cyclophosphamide lumbar injection), 1~3 group of embodiment.
3.3 medication：Matched group gavage from inoculated tumour second day gives normal saline 0.2ml/10g, positive right
Variable concentrations compositionss 0.2ml/10g are given according to group disposable celiac injection cyclophosphamide (1ml/kg), each experimental group gavage, even
Continuous administration 12 days.
3.4 tumor suppressions are observed：Stop administration second day, kill mice solution and take tumor and weigh, by following equation tumour inhibiting rate is calculated：
Tumor control rate (%)=(matched group knurl weight-administration group knurl weight)/matched group knurl weight × 100%.
3.5NK cytoactives are observed：Each animal NK cytoactives are detected with LDH release, effector lymphocyte is each
Group mouse boosting cell, target cell is YAC- cells, and effect target ratio is 50: 1, and every group of cell does three wells, and target cell is set respectively certainly
Right release aperture (Ks), maximum release aperture (Km), experimental port (E).With enzyme-linked immunosorbent assay instrument at 490nm, each Kong Guangmi is detected
Angle value (OD), is calculated as follows NK active：
NK activity (%)=(E-KS/Km-Ks) * 100%.
3.6 lymphocyte proliferation tests are observed：Cell suspension, cell concentration are made with the aseptic each group animal spleen that takes of mtt assay
For 1 × 107/ ml, takes 96 well culture plates, and every group of cell does six multiple holes (0.2ml/ holes), wherein three holes add ConA (final concentration 5mg/
Ml), 37 DEG C are put, 5%CO2Culture 68 hours, takes out, 1000rpm, and 10min is centrifuged, and carefully takes out the μ l of supernatant 100 per hole and abandons
Go, MTT liquid (5mg/ml) 10 μ l are added per hole, continue to cultivate after 4h, add acid isopropyl alcohol, concussion to mix, existed with microplate reader
At 570nm, each hole optical density value (OD) is read, be calculated as follows lymphocyte stimulation indices (SI)：
SI=ConA stimulates hole OD averages/cell control well OD averages.
4th, experimental result is shown in Table 1
Antitumor action of the activity combination of marine life of table 1 to Mice Bearing Lewis Lung Cancer
*P<0.05
Originally test result indicate that medicine of the present invention can significantly activate NK cytoactives, lymhocyte transformation rate is improved, there is bright
Aobvious antitumor action.
Presently preferred embodiments of the present invention is the foregoing is only, not to limit the present invention, all essences in the present invention
Within god and principle, any modification, equivalent substitution and improvements made etc. should be included within the scope of the present invention.
Claims (5)
1. a kind of activity combination of marine life, it is characterised in that in parts by weight, by Concha Ostreae extract 10~30
Part, 2~6 parts of Thallus Laminariae (Thallus Eckloniae) extract, 4~8 parts of Sargassum extract, 5~10 parts of gloiopeltis extract, Hippocampus enzymatic hydrolyzed extract 10~16
Part, 10~16 parts of Stichopus japonicus extract, 4~8 parts of sponge extract, 2~6 parts of cartilage derived extract and ocean actinomycete fermentation liquid 15~
25 parts of compositions.
2. activity combination of marine life according to claim 1, it is characterised in that Thallus Laminariae (Thallus Eckloniae) extract is fucoidan.
3. activity combination of marine life according to claim 1, it is characterised in that marine actinomycete is marine actinomycete
AFN1007。
4. activity combination of marine life according to claim 3, it is characterised in that Sargassum extract is Sargassum polysaccharides,
Gloiopeltis extract is methanolic extract, and cartilage derived extract is the extract of shark liver and cartilage.
5. the pharmaceutical formulation of the activity combination of marine life as described in Claims 1-4 any one, it is characterised in that by
Compositionss described in Claims 1-4 are mixed and made into capsule, granule, oral liquid, pill or punching with pharmaceutical carrier, additive
Agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710110350.7A CN106668077A (en) | 2017-02-27 | 2017-02-27 | Marine bioactive composition and pharmaceutical preparation |
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| CN201710110350.7A CN106668077A (en) | 2017-02-27 | 2017-02-27 | Marine bioactive composition and pharmaceutical preparation |
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ID=58861987
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110637998A (en) * | 2019-11-01 | 2020-01-03 | 青岛浩大生物科技工程有限责任公司 | Composite fermentation type marine functional product |
| CN111346111A (en) * | 2018-12-20 | 2020-06-30 | 扬州蓝色生物医药科技有限公司 | Compound marine traditional Chinese medicine extract and application thereof in aspect of reducing blood sugar |
-
2017
- 2017-02-27 CN CN201710110350.7A patent/CN106668077A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| 梅全喜: "《广东地产药材研究》", 31 May 2011, 广东科技出版社 * |
| 清渠: "《上下五千年难解之谜5》", 31 March 2013, 北京工业大学出版社 * |
| 肖峰: "海洋来源产酶微生物的筛选、鉴定及其外分泌产物的生物学作用探索", 《中国优秀硕士学位论文全文数据库》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111346111A (en) * | 2018-12-20 | 2020-06-30 | 扬州蓝色生物医药科技有限公司 | Compound marine traditional Chinese medicine extract and application thereof in aspect of reducing blood sugar |
| CN111346111B (en) * | 2018-12-20 | 2023-09-15 | 扬州蓝色生物医药科技有限公司 | Compound marine traditional Chinese medicine extract and application thereof in blood glucose reduction |
| CN110637998A (en) * | 2019-11-01 | 2020-01-03 | 青岛浩大生物科技工程有限责任公司 | Composite fermentation type marine functional product |
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Application publication date: 20170517 |