CN107158012A - Application of the Morinda officinalis FOS extract in preventing and treating Alzheimer disease drug, health products or food is prepared - Google Patents
Application of the Morinda officinalis FOS extract in preventing and treating Alzheimer disease drug, health products or food is prepared Download PDFInfo
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- CN107158012A CN107158012A CN201710411670.6A CN201710411670A CN107158012A CN 107158012 A CN107158012 A CN 107158012A CN 201710411670 A CN201710411670 A CN 201710411670A CN 107158012 A CN107158012 A CN 107158012A
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- morinda officinalis
- fos
- extract
- treating alzheimer
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- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 26
- 229940079593 drug Drugs 0.000 title claims abstract description 18
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- 230000036541 health Effects 0.000 title claims abstract description 13
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- 229940029339 inulin Drugs 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/746—Morinda
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Medicinal Chemistry (AREA)
- Botany (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of the Morinda officinalis FOS extract in preventing and treating Alzheimer disease drug, health products or food is prepared, the present invention is studied through interior animal experiment and found, Morinda officinalis FOS extract can significantly improve A β1‑42Cause to intend Senile Dementia Model Rats ability of learning and memory with D galactolipins;Confirmed through animal acute toxicity experiment, Morinda officinalis FOS extract safe-dosaging limits are larger, available for fields such as preventing and treating Alzheimer disease drug, health products and food.
Description
Technical field
The present invention relates to the new application of Morinda officinalis FOS extract, and in particular to Morinda officinalis FOS extract exists
Prepare the application in preventing and treating Alzheimer disease drug, health products or food.
Background technology
Alzheimer disease(Alzheimer's disease, AD)It is a kind of nerve of the progress sexual development of onset concealment
System degenerative disease.Clinically with memory disorders, aphasia, appraxia, agnosia, visual space technical ability infringement, perform function obstacle with
And the performance of the generalized dementia such as personality and behavior change is characterized, the cause of disease is unknown so far.The senile dementia cause of disease and pathogenesis are so far
The present is still not clear, and may have multifactor participation, such as old-age group, heredity, metabolism, head injury history, estrogen deficiency.
Research finds there are very many neurons in the enteron aisle of the mankind, the quantity of these neurons is suitable with brain.Enteron aisle
Neurotransmitter that neuron and cerebral neuron are used, metabolic pathway are almost consistent.From enteric nervous member to cerebral nerve
Member, which has, frequently to communicate, than more than the information interchange from brain to enteron aisle.The communication of enteric microorganism and brain is very frequent, learns
Boundary thinks to form one " bacterium intestines brain axle " between enteron aisle and brain, and intestines brain can influence brain, and brain can also influence intestines brain,
It is two-way intercommunication between them.It is main between both to pass through endosecretory pathway, nerve pathway, immunization route and metabolism way
Footpath influences each other.The communication that the factors such as infection in pregnancy, pollutant, pathogen, diet, inflammation can be all had influence between them.I
Can be intervened by the transplanting of probiotics, diet and caprophyl.
Therefore food, prebiotics, probiotics, plant extracts or the medicine that can influence enteric microorganism structure or ecology are found
Thing etc., the treatment for nerve degenerative diseases is a new way.
Morinda officinalis How is the key medicine tonified the kidney and support yang.Early-stage Study shows that it is rich in oligosaccharides composition, and tool kidney tonifying is helped
Sun, antidepression, anti-osteoporosis and raising ability of learning and memory, immunity and endurance isoreactivity.At present both at home and abroad to bar
The research of halberd day FOS is concentrated mainly in terms of major tranquilizer, immunologic adjuvant, but Morinda officinalis FOS is extracted
The research of application of the thing in preventing and treating Alzheimer's disease is also less.
The content of the invention
Preparing preventing and treating Alzheimer disease drug it is an object of the invention to provide Morinda officinalis FOS extract, protecting
Application in strong product or food.
It is preferred that, the safe-dosaging limits of the Morinda officinalis FOS extract are 30mg/kg-500mg/kg.
It is preferred that, the preparation method of the Morinda officinalis FOS extract comprises the following steps:
(1) general-Morinda officinalis fresh medicine material, goes the removal of impurity, appropriate to crush;
(2) distilled water is added to extract, extract solution is concentrated under reduced pressure, and obtains concentrate;
(3) concentrate is added into ethanol precipitation, precipitation is redissolved plus ethanol reprecipitation through water, obtains Morinda officinalis FOS crude product;
(4) Morinda officinalis FOS crude product is redissolved in water, eluted through anion exchange resin, collect eluent, eluent
Add ethanol precipitation after being concentrated under reduced pressure, stand, suction filtration, dry, produce the oligomeric sugar extract of Morinda officinalis.
It is preferred that, the step(2)Extracting mode be heated to reflux, hot submersion or or diacolation in one or more.
It is preferred that, the step(2)Concretely comprise the following steps:Plus 8-10 times measured distilled water, 1-2h, mistake are boiled
Filter, filter residue adds 8-10 times and measures distilled water again, boils 1-2h, filters, and merging filtrate is concentrated under reduced pressure, and obtains concentrate.
It is preferred that, the step(3)Concretely comprise the following steps:Ethanol is added in concentrate, concentration of alcohol is adjusted to 90%,
Refrigeration, stands 2-24h, precipitation is redissolved in hot water, room temperature is cooled to, and adds ethanol, and regulation concentration of alcohol to 90% is refrigerated,
2-24h is stood, must be precipitated, as Morinda officinalis FOS crude product.
The operation of alcohol precipitation can be redissolved, added to precipitation repeatedly by the present invention through water, miscellaneous preferably to remove alcohol-soluble
Matter.
It is preferred that, the step(4)Concretely comprise the following steps:Morinda officinalis FOS crude product is redissolved in hot water, is cooled to
50 DEG C, pH to 4.5-6.5 is adjusted, solution is continuously eluted through D-900 anion exchange resins with 1.0-1.5BV/h flow velocitys, collected
Eluent, 50-70 DEG C is concentrated under reduced pressure into relative density for 1kg:200ml volumes, add ethanol in concentrate, and regulation ethanol is dense
Degree is to 90%, and refrigeration stands 2-24h, stands, suction filtration, dries, produces the oligomeric sugar extract of Morinda officinalis.
The Morinda officinalis FOS extract obtained using above-mentioned preparation method of the invention, it is combined chemistry discriminating, HPLC,
The technology for detection such as LC-MS, as a result show that it mainly contains plain Morinda offcinalis How, this resistance to sugar, 1F- fruit furyl glycosyls resistance to this sugar, inulin (i.e.
(2 → 1) fruit furyl glycosyl sucrose) a variety of oligosaccharide such as type hexa polyose and seven glycan, yield is more than 30%.
The present invention also provides a kind of medicine for preventing and treating Alzheimer's disease, comprising above-mentioned Morinda officinalis FOS extract and
Pharmaceutically acceptable carrier.
The formulation of medicine of the present invention can be tablet, granule, pulvis, capsule or oral liquid etc., its preparation side
Method is prepared using conventional method.
The present invention compared with prior art, has the advantages that:
The present invention is studied through interior animal experiment and found, Morinda officinalis FOS extract can significantly improve A β 1-42 and D- galas
Sugar causes to intend Senile Dementia Model Rats ability of learning and memory;Confirmed through cell and animal acute toxicity experiment, its safe dose model
Enclose big, available for fields such as preventing and treating Alzheimer disease drug, health products and food.
Brief description of the drawings
Fig. 1 is that Morinda officinalis FOS extract causes the HE of aging model rat intestine, brain pathological tissue to contaminate to D- galactolipins
Chromatic graph.
Fig. 2 is Morinda officinalis FOS extract pairCause dementia rats intestines, heart, the shadow of brain pathological tissue
Ring, and in brain tissueHE dyeing and SABC figure with the influence of Tau protein expression levels.
Embodiment
The present invention is further illustrated below by embodiment, following examples are the specific embodiment party of the present invention
Formula, but embodiments of the present invention are not limited by following embodiments.
Morinda officinalis of the present invention is gathered by Guangdong Deqing city Gao Liang towns Morinda officinalis planting base, is identified as Rubiaceae
The dry root of plant Morinda officinalis.Root oblate cylindricality formula cylinder, slightly curved song, length, diameter 1-2cm, surface lark or
Grey yellowish-brown, some micro-strip purples, the vertical wrinkle of tool and the band got deeply stuck in, what is had exposes wood in contracting shape or skin zone's transverse direction dialysis is hung
Portion, shape such as chicken intestines.Matter is tough and tensile, and plane of rupture is uneven, skin zone thickness 5-7mm, lavender, woody part diameter 2-4mm.Gas is micro-, bitter, slightly
It is puckery.
Embodiment 1:The preparation of Morinda officinalis FOS extract
Specifically include following steps:
By Morinda officinalis fresh medicine material, the removal of impurity is gone, it is appropriate to crush;Plus 8 times of amount distilled water, 2h is boiled, is filtered,
Filter residue adds 8 times of amount distilled water again, boils 2h, filters, merging filtrate is concentrated under reduced pressure, and obtains concentrate;Add in concentrate
Enter ethanol, regulation concentration of alcohol to 90%, refrigeration stands 24h, precipitation is redissolved in hot water, room temperature is cooled to, ethanol is added,
Concentration of alcohol is adjusted to 90%, refrigeration stands 24h, must precipitated, as Morinda officinalis FOS crude product;By Morinda officinalis FOS
Crude product is redissolved in hot water, is cooled to 50 DEG C, adjusts pH to 5.0, solution is through D-900 anion exchange resins, with 1.0-1.5BV/h
Flow velocity is continuously eluted, and collects eluent, and 50-70 DEG C is concentrated under reduced pressure into relative density for 1kg:200ml volumes, add in concentrate
Enter ethanol, regulation concentration of alcohol to 90%, refrigeration stands 2-24h, stood, suction filtration, dries, and produces the extraction of Morinda officinalis oligosaccharide
Thing.
By above-mentioned Morinda officinalis FOS extract(OMO)Carry out the test of pesticide effectiveness:
Test example one:Morinda officinalis FOS extract improves D- galactolipins and causes to intend Senile Dementia Model Rats ability of learning and memory
Tested with SPF grades of SD rats, using long-term intraperitoneal injection D- galactolipin method modelings, prepare aging Model of Dementia.Make
After mould, Normal group, model group are respectively with 2 mL/d physiological saline gavages, OMO low dose groups(50 mg/kg/d), OMO it is high
Dosage group(100 mg/kg/d), Morinda officinalis FOS extract OMO treatments are given by respective dosage gavage, each group is persistently given
Medicine 8 weeks.After 8 weeks, pass through Morris water mazes(MWM)To assess the Spatial memory ability to rat, 1, table the results are shown in Table
2, Fig. 1.
The oligomeric sugar extract of the Morinda officinalis of table 1. causes aging model rat water maze to test preclinical influence D- galactolipins
As a result(n=6)
The oligomeric sugar extract of the Morinda officinalis of table 2. causes the influence result of aging model rat water maze test platform phase to D- galactolipins
(n=6)
As can be seen from Table 1, the different testing time points of latency test, compared with normal group, model group incubation period is notable
Extension, difference has statistical significance (P<0.05), this experimental model is pointed out to be successfully prepared.Compared with model group, each administration
Group incubation period substantially shortens, and wherein OMO high doses group is better than OMO low dose groups (P<0.05).
As can be seen from Table 2, normal rats are in third quadrant(Quadrant i.e. where platform original)Swimming timeIt is longer than other quadrants, difference has conspicuousness, illustrates that rat is remembered to platform formation.With normal group
Compare, model group is in third quadrant swimming timeIt is appreciably shorter, illustrate that D- galactolipins have infringement big
Mouse memory function;Compared with model group, OMO high doses group is in third quadrant swimming timeIt is obviously prolonged
(P<0.05), prompting Morinda officinalis FOS extract, which has, improves the cause Rats With Memory dysfunction effect of D- galactolipins.
As seen from Figure 1, model group small intestine cells(Intestin)Shrinkage, cell is irregular, and each administration group small intestine is thin
Born of the same parents are more smooth, regular shape, full.Brain stem(Brainstem)In, model group inflammatory cell number is significantly more than each administration
Group, points out administration group to mitigate the inflammatory reaction of cell.Cerebellum(cerebellum)In, compared with model group, each administration group
Cell number showed increased.
Therefore, from the above, it is seen that Morinda officinalis FOS extract, which can improve D- galactolipins, causes plan senile dementia
Rat model ability of learning and memory, reduces tissue inflammation reaction.
Test example two:Morinda officinalis FOS extract improvesCause to intend Senile Dementia Model Rats learning and memory
Ability
Tested, injected using in bilateral hippocampus with SPF grades of SD ratsMethod modeling, prepares aging Model of Dementia.Make
After mould, Normal group, model group are respectively with 2 mL/d physiological saline gavages, OMO low dose groups(50 mg/kg/d), OMO it is high
Dosage group(100 mg/kg/d), Morinda officinalis FOS extract OMO treatments are given by respective dosage gavage, each group is persistently given
Medicine 4 weeks.After 4 weeks, pass through Morris water mazes(MWM)To assess the Spatial memory ability to rat, 3, table are the results are shown in Table
4, Fig. 2.
The oligomeric sugar extract pair of the Morinda officinalis of table 3.Cause the preclinical influence knot of dementia rats water maze test
Really(n=6)
The oligomeric sugar extract pair of the Morinda officinalis of table 4.Cause the influence result of Model of Dementia water maze test platform phase(n=
6)
As can be seen from Table 3, the different testing time points of latency test, compared with normal group, model group incubation period is notable
Extension, difference has statistical significance(P<0.05), point out this experimental model to be successfully prepared.Compared with model group, each administration
Group incubation period substantially shortens, and wherein OMO high doses group is better than OMO low dose groups.
As can be seen from Table 4, in third quadrant(Quadrant i.e. where platform original)Swimming time, compared with model group, respectively
Administration group swimming time significantly extends (P<0.05), the prompting oligomeric sugar extract of Morinda officinalis can improve A β 1-42 and cause to intend old silly
Slow-witted rat model ability of learning and memory.
As seen from Figure 2, compared with model group, in each administration group, small intestine(Intestin)Cell more light is full
It is regular, heart(Heart)Space between cells diminishes, brain(Brain)Cell number showed increased,With the table of Tau albumen
Reduced up to amount, point out the oligomeric sugar extract of Morinda officinalis to improve the function and form of rat tissue's cell, substantially reduce A Er
Ci Haimo disease GAP-associated protein GAPsWith Tau expression.
Therefore, from the above, it is seen that the oligomeric sugar extract of Morinda officinalis, which can improve A β 1-42, causes plan Senlie dementia model
Learning and memory in rats ability, is reducedWith the expression of Tau albumen.
Safety evaluatio:
Toxicity test, according to《Chinese medicine, natural drug peace comment technological guidance's principle》, Morinda officinalis FOS extract dosage model
Enclose for 30mg/kg-500mg/kg.Maximum dosage-feeding 500mg/kg gavages give kunming mice, and Continuous Observation 14 days does not have animal
It is dead.Show that the safe-dosaging limits of Morinda officinalis FOS extract are larger, drug safety.
Application examples:The preparation of granule containing Morinda officinalis FOS extract
Active ingredient:65 parts of Morinda officinalis FOS extract;
Auxiliary material:25 parts of pregelatinized starch, 4 parts of superfine silica gel powder, 6 parts of magnesium stearate.
Preparation technology:By Morinda officinalis FOS extract, pregelatinized starch, superfine silica gel powder, magnesium stearate input mixing
It is well mixed in machine.
Above-mentioned compound is packed into capsule by fully-automatic capsule filler, produced.
Claims (9)
1. application of the Morinda officinalis FOS extract in preventing and treating Alzheimer disease drug, health products or food is prepared.
2. Morinda officinalis FOS extract according to claim 1 is preparing preventing and treating Alzheimer disease drug, health care
Application in product or food, it is characterised in that the safe-dosaging limits of the Morinda officinalis FOS extract are 30mg/kg-
500mg/kg。
3. Morinda officinalis FOS extract according to claim 1 is preparing preventing and treating Alzheimer disease drug, health care
Application in product or food, it is characterised in that the preparation method of the Morinda officinalis FOS extract comprises the following steps:
(1)By Morinda officinalis fresh medicine material, the removal of impurity is gone, it is appropriate to crush;
(2)Plus distilled water is extracted, extract solution is concentrated under reduced pressure, and obtains concentrate;
(3)By concentrate plus ethanol precipitation, precipitation is redissolved plus ethanol reprecipitation through water, obtains Morinda officinalis FOS crude product;
(4)Morinda officinalis FOS crude product is redissolved in water, eluted through anion exchange resin, eluent, eluent is collected
Add ethanol precipitation after being concentrated under reduced pressure, stand, suction filtration, dry, produce the oligomeric sugar extract of Morinda officinalis.
4. Morinda officinalis FOS extract according to claim 1 is preparing preventing and treating Alzheimer disease drug, health care
Application in product or food, it is characterised in that the step(2)The mode of middle extraction is is heated to reflux, in hot submersion or diacolation
One or more.
5. Morinda officinalis FOS extract according to claim 4 is preparing preventing and treating Alzheimer disease drug, health care
Application in product or food, it is characterised in that the step(2)Concretely comprise the following steps:Plus 8-10 times measured distilled water, 1- is boiled
2h, filtering, filter residue adds 8-10 times and measures distilled water again, boils 1-2h, filters, and merging filtrate is concentrated under reduced pressure, and obtains concentrate.
6. Morinda officinalis FOS extract according to claim 1 is preparing preventing and treating Alzheimer disease drug, health care
Application in product or food, it is characterised in that the step(3)Concretely comprise the following steps:Ethanol is added in concentrate, second is adjusted
Determining alcohol is to 90%, and refrigeration stands 2-24h, precipitation is redissolved in hot water, room temperature is cooled to, and adds ethanol, and regulation ethanol is dense
Degree is to 90%, and refrigeration stands 2-24h, must precipitated, as Morinda officinalis FOS crude product.
7. Morinda officinalis FOS extract according to claim 1 is preparing preventing and treating Alzheimer disease drug, health care
Application in product or food, it is characterised in that the step(4)Concretely comprise the following steps:Morinda officinalis FOS crude product is redissolved
In hot water, 50 DEG C are cooled to, pH to 4.5-6.5 is adjusted, solution is through D-900 anion exchange resins, with 1.0-1.5BV/h flow velocitys
Continuous elution, collects eluent, and 50-70 DEG C is concentrated under reduced pressure into relative density for 1kg:200ml volumes, add second in concentrate
Alcohol, regulation concentration of alcohol to 90%, refrigeration stands 2-24h, stands, suction filtration, dries, produces the oligomeric sugar extract of Morinda officinalis.
8. a kind of medicine for preventing and treating Alzheimer's disease, includes Morinda officinalis FOS extract and pharmaceutically acceptable load
Body.
9. a kind of medicine for preventing and treating Alzheimer's disease according to claim 8, it is characterised in that the formulation of the medicine
For tablet, granule, pulvis, capsule or oral liquid.
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CN107812019A (en) * | 2017-11-27 | 2018-03-20 | 广东省微生物研究所(广东省微生物分析检测中心) | A kind of probiotics of the FOS containing Morinda officinalis and its production and use |
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GB2590624B (en) * | 2019-12-20 | 2023-08-30 | Green Bioactives Ltd | Composition comprising one or more fructooligosaccharide(s) and L-theanine |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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CN107811991A (en) * | 2017-11-27 | 2018-03-20 | 广东省微生物研究所(广东省微生物分析检测中心) | The preparation method of the enteric coated preparations of the FOS containing Morinda officinalis and the preparation being prepared |
CN107812019A (en) * | 2017-11-27 | 2018-03-20 | 广东省微生物研究所(广东省微生物分析检测中心) | A kind of probiotics of the FOS containing Morinda officinalis and its production and use |
CN107812019B (en) * | 2017-11-27 | 2021-01-29 | 广东省微生物研究所(广东省微生物分析检测中心) | Microecological preparation containing morinda officinalis fructo-oligosaccharide and preparation method and application thereof |
GB2590624B (en) * | 2019-12-20 | 2023-08-30 | Green Bioactives Ltd | Composition comprising one or more fructooligosaccharide(s) and L-theanine |
CN113278081A (en) * | 2021-04-25 | 2021-08-20 | 广州医科大学附属第五医院 | Morinda officinalis oligosaccharide and preparation method and application thereof |
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