CN112641820A - NMN-containing pharmaceutical composition for improving climacteric symptoms - Google Patents

NMN-containing pharmaceutical composition for improving climacteric symptoms Download PDF

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CN112641820A
CN112641820A CN202011538351.XA CN202011538351A CN112641820A CN 112641820 A CN112641820 A CN 112641820A CN 202011538351 A CN202011538351 A CN 202011538351A CN 112641820 A CN112641820 A CN 112641820A
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extract
nmn
pharmaceutical composition
momordica grosvenori
suaeda
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沈洁
沈艳
宋芸娟
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Shenzhen Hopelife Biotechnology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/42Cucurbitaceae (Cucumber family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
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    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps

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Abstract

The invention provides a pharmaceutical composition containing NMN for improving climacteric symptoms, which comprises NMN, an suaeda salsa extract, a momordica grosvenori extract and other pharmaceutically acceptable auxiliary materials, wherein the suaeda salsa extract is extracted from stems and tender shoots of overground parts of suaeda salsa and suaeda salsa seeds, and the momordica grosvenori extract is extracted from momordica grosvenori pulp and momordica grosvenori pericarp. The components in the pharmaceutical composition provided by the invention adopt proper compatibility proportion, and take effect synergistically, so that climacteric symptoms are improved.

Description

NMN-containing pharmaceutical composition for improving climacteric symptoms
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to a pharmaceutical composition containing NMN for improving climacteric symptoms.
Background
The female climacteric syndrome refers to a series of mental and physical manifestations of female, such as vegetative nerve functional disturbance, reproductive system atrophy and the like, caused by the reduction of sex hormone content before and after menopause, and a series of physiological and psychological changes, such as anxiety, depression, sleep disorder and the like, can also occur. The female climacteric syndrome is mostly seen in women of 46-50 years old, and the onset age is advanced and the incidence rate is increased in recent years.
At present, the treatment method commonly adopted for the quality of climacteric syndrome is hormone replacement therapy, namely artificially synthesized hormones such as cromolon, nilestriol and ethinylestradiol are added into a patient for replacement treatment, but the effect of the artificially synthesized hormones is obvious after the patient takes the artificially synthesized hormones for a short time, but the artificially synthesized hormones can generate a plurality of toxic and side effects on the body after the patient takes the artificially synthesized hormones for a long time, such as hysteromyoma, endometriosis and climacteric dysfunctional uterine bleeding, and malignant tumors such as endometrial cancer and breast cancer are easily induced seriously. In addition, hormone drugs with small side effects in recent years can obviously reduce toxic and side effects, but have more requirements on people taking the drugs and have very strict requirements on the dosage of the drugs.
Therefore, the development of a medicament for treating the climacteric syndrome of women with obvious effect is one of the important subjects of technical developers in the field.
Disclosure of Invention
In view of the above, the present invention provides a pharmaceutical composition containing NMN for improving climacteric symptoms and a preparation method thereof, aiming to overcome the defects in the prior art.
In order to achieve the purpose, the technical scheme of the invention is realized as follows:
a pharmaceutical composition containing NMN for improving climacteric symptoms comprises NMN, Suaeda glauca extract, fructus momordicae extract and other pharmaceutically acceptable auxiliary materials, wherein the Suaeda glauca extract is obtained by extracting stems and tender shoots of overground parts of Suaeda glauca and Suaeda glauca seeds, and the fructus momordicae extract is obtained by extracting fruit pulp of fructus momordicae and fruit peel of fructus momordicae.
Preferably, the mass ratio of the NMN to the suaeda glauca extract to the momordica grosvenori extract is 1: (50-300): (10-200).
Preferably, the mass ratio of the NMN to the suaeda glauca extract to the momordica grosvenori extract is 1: (150-200): (50-150).
Preferably, the mass ratio of the NMN to the suaeda glauca extract to the momordica grosvenori extract is 1: 150: 120.
preferably, the preparation method of the suaeda glauca extract comprises the following steps:
(1) respectively taking stems and tender shoots of overground parts of the suaeda glauca bunge as raw materials, grinding the raw materials, adding an organic reagent, and uniformly mixing;
(2) performing ultrasonic wall breaking on the mixture, adding an ethanol water solution as an extraction solvent, extracting by a hot reflux extraction method for 2-4 times, combining the extracting solutions, filtering, concentrating the extracting solution, recovering ethanol, and drying the concentrated solution to a solid state to obtain an extract A;
(3) pulverizing dried Suaeda glauca seeds, mixing with cellulase completely for enzymolysis, adding 3-5 times volume of water, boiling, deactivating enzyme at high temperature, vacuum filtering, collecting filtrate, and concentrating under reduced pressure;
(4) adding 2-3 times of 95% ethanol into the concentrated filtrate, leaching, treating the leaching solution in microwave for 10min, vacuum filtering, collecting filtrate, concentrating under pressure, and drying to obtain extract B;
(5) mixing the extract A and the extract B, and grinding to obtain the suaeda glauca extract.
Preferably, the mass ratio of the extract A to the extract B is (2-10): (5-20).
Preferably, the mass ratio of the extract A to the extract B is (2-5): (5-15).
Preferably, the preparation method of the momordica grosvenori extract comprises the following steps:
(1) adding 40-60% ethanol into fructus Siraitiae Grosvenorii pulp powder or fresh fructus Siraitiae Grosvenorii pericarp cell culture, mixing, and breaking wall by ultrasonic wave to obtain solution C and solution D;
(2) adding 5-10 times of pure water into the solution C and the solution D, and leaching at 80-120 deg.C to obtain a leaching product E and a leaching product F;
(3) respectively centrifuging or suction-filtering the leaching product E and the leaching product F to perform solid-liquid separation, and reserving liquid to obtain a pretreatment product M and a pretreatment product N;
(4) mixing the pretreatment product M and the pretreatment product N according to the mass ratio of (1-10) to 1, concentrating, and freeze-drying to obtain the fructus momordicae extract.
Preferably, the weight part ratio of the pretreatment product M to the pretreatment product N is 7: 1.
the invention also provides a preparation method of the NMN-containing pharmaceutical composition for improving climacteric symptoms, which comprises the following steps:
weighing NMN, suaeda glauca extract and fructus momordicae extract according to the formula ratio, and mixing to obtain the pharmaceutical composition; adding a proper amount of pharmaceutically acceptable auxiliary materials into the medicinal composition, and forming the preparation to obtain the traditional Chinese medicine.
In the present invention, the term "pharmaceutically acceptable excipient" includes pharmaceutically acceptable carriers, excipients, diluents and the like, which are compatible with the pharmaceutically active ingredient. The use of pharmaceutically acceptable excipients for the preparation of pharmaceutical preparations is well known to those skilled in the art.
The pharmaceutical composition of the present invention is prepared by combining the pharmaceutical composition with pharmaceutically acceptable adjuvants (such as carriers, excipients, diluents, etc. well known to those skilled in the art) to prepare various preparations, preferably solid preparations and liquid preparations, such as tablets, pills, capsules, powders, suspensions, granules, syrups, emulsions, suspensions, etc., and various sustained release formulations, preferably in oral administration forms.
The invention also provides application of the pharmaceutical composition for improving climacteric symptoms.
Compared with the prior art, the invention has the following advantages:
the components in the pharmaceutical composition provided by the invention adopt proper compatibility proportion, and take effect synergistically, so that climacteric symptoms are improved. The inventor unexpectedly finds that the pesticide effect can be obviously improved by taking stems and tender shoots of overground parts of the suaeda glauca and suaeda glauca seeds as extraction raw materials and taking fruit pulp and fruit peel of the momordica grosvenori as extraction raw materials and simultaneously mixing and extracting the raw materials in a proper proportion.
Detailed Description
Unless defined otherwise, technical terms used in the following examples have the same meanings as commonly understood by one of ordinary skill in the art to which the present invention belongs. The test reagents used in the following examples, unless otherwise specified, are all conventional biochemical reagents; the experimental methods are conventional methods unless otherwise specified.
The invention will be described in detail with reference to the following examples.
Example 1 preparation of Suaeda extract
(1) Respectively taking stems and tender shoots of overground parts of the suaeda glauca bunge as raw materials, grinding the raw materials, adding an organic reagent, and uniformly mixing;
(2) performing ultrasonic wall breaking on the mixture, adding an ethanol water solution as an extraction solvent, extracting by a hot reflux extraction method for 4 times, mixing the extracting solutions, filtering, concentrating the extracting solution, recovering ethanol until the concentrated solution is thick paste, and drying to a solid state to obtain an extract A;
(3) crushing dried suaeda glauca seeds, fully mixing the crushed suaeda glauca seeds with cellulase for enzymolysis, adding water with volume 5 times of that of the crushed suaeda glauca seeds for boiling treatment, performing suction filtration after enzyme deactivation at high temperature, collecting filtrate, and performing reduced pressure concentration;
(4) adding 3 times of 95% ethanol into the concentrated filtrate, leaching, treating the leaching solution in microwave for 10min, vacuum filtering, collecting filtrate, concentrating under pressure, and drying to obtain extract B;
(5) mixing and grinding the extract A and the extract B according to the mass ratio of 1:2 to obtain the suaeda glauca extract.
Example 2 preparation of Momordica grosvenori extract
(1) Adding 40-60% ethanol into fructus Siraitiae Grosvenorii pulp powder or fresh fructus Siraitiae Grosvenorii pericarp cell culture, mixing, and breaking wall by ultrasonic wave to obtain solution C and solution D;
(2) adding 5 times of pure water into the solution C and the solution D, and leaching at 100 ℃ to obtain a leaching product E and a leaching product F;
(3) respectively centrifuging or suction-filtering the leaching product E and the leaching product F to perform solid-liquid separation, and reserving liquid to obtain a pretreatment product M and a pretreatment product N;
(4) and mixing the pretreatment product M and the pretreatment product N in a mass ratio of 7:1, concentrating, and freeze-drying to obtain the fructus momordicae extract.
EXAMPLE 3 preparation of pharmaceutical composition
TABLE 1 ingredient Table of pharmaceutical composition
Group of NMN/g Suaeda glauca extract/g Momordica grosvenori extract/g
1 1 150 120
2 1 150 50
3 1 200 150
4 1 50 10
5 1 300 200
The NMN, the suaeda glauca extract and the momordica grosvenori extract are mixed according to the proportion in the table 1 to prepare the pharmaceutical compositions 1, 2, 3, 4 and 5.
In addition, in order to verify the compounding effect of the suaeda glauca extract and the momordica grosvenori extract, the preparation of 6-11 groups of pharmaceutical compositions is added, and the specific components are shown in table 2.
TABLE 2 ingredient Table of pharmaceutical composition
Figure BDA0002853832570000061
Figure BDA0002853832570000071
Note: adjuvants are not the focus of the invention and are therefore not added in the experiments, only the relationship between the extract and NMN is investigated.
Test examples sleep improvement test
Healthy Kunming mice are taken, 140 mice with the weight of 20 +/-2 g are randomly divided into 14 groups, 10 mice in each group, and 5 mice are male and female respectively. The pharmaceutical compositions 1-11 were dissolved in 0.5ml of physiological saline, and the gavage was performed in the order of table 1 and table 2, and the administration doses were: based on the mass of the NMN being 300 ng/piece/day, an NMN control group and a blank control group are added at the same time, wherein the NMN control group is only filled with gastric NMN, the administration dosage is 300 ng/piece/day, and the blank control group is filled with 0.5ml/g of normal saline every day. The administration was continued for 5 days. 1h after the last drug, the mice are gavaged with pentobarbital sodium at a dose of 35mg/kg, and the sleep time of the mice is recorded by taking the disappearance of the righting reflex as an index. The test results are shown in Table 3.
TABLE 3 sleep time test results
Figure BDA0002853832570000072
Figure BDA0002853832570000081
Note: compared with the blank control group, the composition of the composition,*P<0.05,**P<0.01
as can be seen from Table 3, the traditional Chinese medicine composition provided by the invention can obviously prolong the sleep time and improve the sleep quality. As can be seen from the comparison of the data of the 6-11 groups with the data of the 1-5 groups, the compound administration of the NMN, the suaeda salsa extract and the momordica grosvenori extract is obviously superior to the single administration of the NMN, and simultaneously, the proper proportion of the NMN, the suaeda salsa extract and the momordica grosvenori extract can achieve better effect. In conclusion, the traditional Chinese medicine composition has excellent curative effect on improving the sleep quality of climacteric patients.
Test examples SOD Activity and MDA content test
Animal grouping and handling
Healthy second-class female Kunming mice are taken, the weight of the mice is 20 +/-2 g, 140 mice are randomly divided into 14 groups, and 10 mice are taken. The pharmaceutical compositions 1-11 were dissolved in 0.5ml of physiological saline, and the gavage was performed in the order of table 1 and table 2, and the administration doses were: the quality of NMN is 300 ng/piece/day, D-galactose is injected into the abdominal cavity at the same time, and the injection dosage is 0.3 mg/g; the NMN control group is gastric lavage NMN, the administration dosage is 300 ng/piece/day, and D-galactose is injected into the abdominal cavity at the same time, the injection dosage is 0.3 mg/g; the blank control group was gavaged with 0.3ml/g of normal saline daily, and was injected intraperitoneally with 0.3mg/g of normal saline simultaneously. The model group is that the stomach is irrigated with 0.3ml/g normal saline every day, and D-galactose is injected into the abdominal cavity at the same time, and the injection dosage is 0.3 mg/g. The administration is continued for 60 days.
Measurement method
Taking a brain tissue sample of a mouse, adding physiological saline according to the proportion of 1:5, homogenizing in a water bath environment, centrifuging for 10 minutes at 1500r/min, taking 20 microliters of supernatant, and determining SOD activity and MDA content in the brain tissue, wherein the kit is purchased from Nanjing to build a biological research institute, and the coomassie brilliant blue kit is used for tissue protein determination according to the instruction. The test results are shown in Table 4.
TABLE 4 data of MDA content and SOD activity in brain tissue of each group of mice
Group of MDA(nmol/mg) SOD(U/ml)
1 14.09±2.09** 135±13.11**
2 16.21±1.95* 130±14.64*
3 15.77±3.07* 131±13.98*
4 15.31±1.30* 127±18.10**
5 18.06±1.64** 130±17.90**
6 18.91±1.82* 128±15.33
7 19.70±2.33* 120±16.37**
8 19.64±2.90* 121±16.91*
9 20.11±1.56* 123±19.55*
10 22.43±1.71* 119±18.07**
11 21.20±2.14* 119±16.41*
NMN control group 22.90±3.03** 115±15.97**
Blank control group 23.84±1.94** 103±16.13*
Model set 25.11±1.73## 115±18.01##
Note: compared with the normal control, the method has the advantages that,##p is less than 0.01; in comparison with the set of models,*P<0.05,**P<0.01。
as shown in the results in Table 4, the MDA content of the Chinese medicinal composition is reduced compared with that of the control group, and the SOD activity is lower than that of the control group. As can be seen from the comparison of the data of the 6-11 groups with the data of the 1-5 groups, the compound administration of the NMN, the suaeda salsa extract and the momordica grosvenori extract is obviously superior to the single administration of the NMN, and simultaneously, the proper proportion of the NMN, the suaeda salsa extract and the momordica grosvenori extract can achieve better effect. In conclusion, the traditional Chinese medicine composition can obviously enhance the activity of SOD in organisms, remove excessive free radicals and possibly prevent the damage of the free radicals to cells and matrixes thereof.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the invention, so that any modifications, equivalents, improvements and the like, which are within the spirit and principle of the present invention, should be included in the scope of the present invention.

Claims (10)

1. A pharmaceutical composition for improving climacteric symptoms comprising NMN, characterized in that: the suaeda salsa extract is obtained by extracting stems and tender shoots of overground parts of suaeda salsa and suaeda salsa seeds, and the momordica grosvenori extract is obtained by extracting momordica grosvenori pulp and momordica grosvenori pericarp.
2. The NMN-containing pharmaceutical composition for improving climacteric symptoms according to claim 1, characterized in that: the mass ratio of the NMN to the suaeda glauca extract to the momordica grosvenori extract is 1: (50-300): (10-200).
3. The NMN-containing pharmaceutical composition for improving climacteric symptoms according to claim 2, characterized in that: the mass ratio of the NMN to the suaeda glauca extract to the momordica grosvenori extract is 1: (150-200): (50-150).
4. The NMN-containing pharmaceutical composition for improving climacteric symptoms according to claim 3, characterized in that: the mass ratio of the NMN to the suaeda glauca extract to the momordica grosvenori extract is 1: 150: 120.
5. the NMN-containing pharmaceutical composition for improving climacteric symptoms according to claim 1, characterized in that: the preparation method of the suaeda glauca extract comprises the following steps:
(1) respectively taking stems and tender shoots of overground parts of the suaeda glauca bunge as raw materials, grinding the raw materials, adding an organic reagent, and uniformly mixing;
(2) performing ultrasonic wall breaking on the mixture, adding an ethanol water solution as an extraction solvent, extracting by a hot reflux extraction method for 2-4 times, combining the extracting solutions, filtering, concentrating the extracting solution, recovering ethanol, and drying the concentrated solution to a solid state to obtain an extract A;
(3) pulverizing dried Suaeda glauca seeds, mixing with cellulase completely for enzymolysis, adding 3-5 times volume of water, boiling, deactivating enzyme at high temperature, vacuum filtering, collecting filtrate, and concentrating under reduced pressure;
(4) adding 2-3 times of 95% ethanol into the concentrated filtrate, leaching, treating the leaching solution in microwave for 10min, vacuum filtering, collecting filtrate, concentrating under pressure, and drying to obtain extract B;
(5) mixing the extract A and the extract B, and grinding to obtain the suaeda glauca extract.
6. The NMN-containing pharmaceutical composition for improving menopausal symptoms according to claim 5, wherein: the mass ratio of the extract A to the extract B is (2-10): (5-20).
7. The NMN-containing pharmaceutical composition for improving menopausal symptoms according to claim 6, wherein: the mass ratio of the extract A to the extract B is (2-5): (5-15).
8. The NMN-containing pharmaceutical composition for improving climacteric symptoms according to claim 1, characterized in that: the preparation method of the momordica grosvenori extract comprises the following steps of:
(1) adding 40-60% ethanol into fructus Siraitiae Grosvenorii pulp powder or fresh fructus Siraitiae Grosvenorii pericarp cell culture, mixing, and breaking wall by ultrasonic wave to obtain solution C and solution D;
(2) adding 5-10 times of pure water into the solution C and the solution D, and leaching at 80-120 deg.C to obtain a leaching product E and a leaching product F;
(3) respectively centrifuging or suction-filtering the leaching product E and the leaching product F to perform solid-liquid separation, and reserving liquid to obtain a pretreatment product M and a pretreatment product N;
(4) mixing the pretreatment product M and the pretreatment product N according to the mass ratio of (1-10) to 1, concentrating, and freeze-drying to obtain the fructus momordicae extract; preferably, the weight part ratio of the pretreatment product M to the pretreatment product N is 7: 1.
9. a method for preparing a pharmaceutical composition for improving menopausal symptoms comprising NMN according to any one of claims 1 to 8, wherein: the method comprises the following steps:
weighing NMN, suaeda glauca extract and fructus momordicae extract according to the formula ratio, and mixing to obtain the pharmaceutical composition; adding a proper amount of pharmaceutically acceptable auxiliary materials into the medicinal composition, and forming the preparation to obtain the traditional Chinese medicine.
10. Use of a pharmaceutical composition according to any one of claims 1 to 9 for improving climacteric symptoms.
CN202011538351.XA 2020-12-23 2020-12-23 NMN-containing pharmaceutical composition for improving climacteric symptoms Pending CN112641820A (en)

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Citations (2)

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Publication number Priority date Publication date Assignee Title
CN110237104A (en) * 2019-07-01 2019-09-17 北京科佑爱科技有限责任公司 It is suitable for the health-oriented products composition of adult female, old man and sub-health state crowd
US20200009170A1 (en) * 2016-09-13 2020-01-09 Megumi Tanaka Sleep display agent property and method for improving sleep disorders

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200009170A1 (en) * 2016-09-13 2020-01-09 Megumi Tanaka Sleep display agent property and method for improving sleep disorders
CN110237104A (en) * 2019-07-01 2019-09-17 北京科佑爱科技有限责任公司 It is suitable for the health-oriented products composition of adult female, old man and sub-health state crowd

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
姜洋: "补肾祛瘀化痰法对轻度认知功能损害患者认知功能及氧化应激影响的研究", 《中国博士学位论文全文数据库 医药卫生科技辑》 *
胥德政: "白藜芦醇对衰老模型小鼠的抗衰老作用", 《中国老年学杂志》 *
陈路: "培补肝肾复方治疗帕金森病及其肠功能障碍的疗效研究", 《中国博士学位论文全文数据库 医药卫生科技辑》 *

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