CN113288920A - Application of cannabidiol monomer and lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Parkinson's disease - Google Patents
Application of cannabidiol monomer and lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Parkinson's disease Download PDFInfo
- Publication number
- CN113288920A CN113288920A CN202110647548.5A CN202110647548A CN113288920A CN 113288920 A CN113288920 A CN 113288920A CN 202110647548 A CN202110647548 A CN 202110647548A CN 113288920 A CN113288920 A CN 113288920A
- Authority
- CN
- China
- Prior art keywords
- cannabidiol
- monomer
- lactobacillus plantarum
- disease
- parkinson
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- 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
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation 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
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation 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
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Psychology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The application of the combination of the cannabidiol monomer and the lactobacillus plantarum DP189 in the preparation of the medicine for preventing and/or treating the Parkinson disease belongs to the field of functional food microorganisms, wherein the concentration of the cannabidiol monomer is 2.4 mg/mL; the concentration of Lactobacillus plantarum DP189 was 109～1010CFU/mL; cannabidiol monomer was used separately from lactobacillus plantarum DP 189. The cannabidiol monomer and the lactobacillus plantarum DP189 strain are jointly applied to improve the behavioral ability of a Parkinson disease model mouse; inhibiting apoptosis of cerebral neurons of a Parkinson disease model mouse; reducing inflammatory response, reducing the levels of inflammatory factors TNF-alpha, IL-1 beta and IL-6; small model for preventing Parkinson's diseaseOxidative stress in mice, reducing the level of oxidative stress.
Description
Technical Field
The invention belongs to the technical field of functional food microorganisms, and particularly relates to an application of a cannabidiol monomer and lactobacillus plantarum DP189 in preparation of a medicine for preventing and/or treating Parkinson's disease.
Background
Parkinson's Disease (PD) is a degenerative disease of the nervous system, about 1% of people over 60 years old worldwide suffer from the disease, and the prevalence rate of PD in people over 65 years old in China is about 1.7%. The main pathological features of PD are loss of dopaminergic neurons of the mesocerebral substantia nigra leading to dysfunction of the nigrostriatal system in locomotion, resulting in behavioral changes in muscle tremor, rigidity, bradykinesia and postural instability. The non-behavioral symptoms mainly comprise intestinal dysfunction, hyposmia, sleep disorder, cognitive impairment and the like, and can appear decades earlier than the dyskinesia, wherein the intestinal dysfunction is the most common non-motor symptom in the early stage of PD, which indicates that the PD possibly starts from the intestinal tract.
Although monoamine oxidase type B inhibitors such as levodopa (L-DOPA) and the like have been shown to have protective and ameliorating effects on damage to the nervous system, the currently discovered drugs are also only symptomatic treatments for PD against clinical symptoms. Based on the above, the search for a safe and effective drug is of great significance for the treatment of PD.
Disclosure of Invention
The invention aims to provide application of a cannabidiol monomer and lactobacillus plantarum DP189 in preparation of a medicine for preventing and/or treating Parkinson's disease.
The technical scheme adopted by the invention for solving the technical problem is as follows:
the cannabidiol monomer and the lactobacillus plantarum DP189 are combined to prepare the medicine for preventing and/or treating the Parkinson disease.
As a preferred embodiment, the concentration of cannabidiol monomer is 2.4 mg/mL; the concentration of the lactobacillus plantarum DP189 is 109～1010CFU/mL; the cannabidiol monomer is used separately from lactobacillus plantarum DP 189.
As a preferred embodiment, said lactobacillus plantarum DP189 has been deposited in the chinese type culture collection at 2019, 3 and 25 months, with the deposit numbers: CCTCC NO: and M2019199.
In a preferred embodiment, the Lactobacillus plantarum DP189 is used by suspending it in 2% Tween-80 physiological saline at a concentration of 109～1010CFU/mL。
In a preferred embodiment, the cannabidiol monomer is used dissolved in 2% tween-80 saline at a concentration of 2.4 mg/mL.
In a preferred embodiment, the cannabidiol monomer has a purity of 99% or greater.
As a preferred embodiment, the cannabidiol monomer is prepared using the following method:
selecting fresh industrial hemp leaves, and air-drying; weighing air-dried industrial hemp flower leaves, adding 20 times of food-grade 95% ethanol, heating, refluxing and extracting for two times, filtering, combining filtrates, and recovering solvent under reduced pressure to obtain extract containing cannabidiol monomer; adding the extract into ethyl acetate according to the weight ratio of the extract to the ethyl acetate of 1:10, and extracting with water; standing overnight, removing water layer, recovering ethyl acetate layer under reduced pressure to obtain cannabinol crude product containing cannabidiol monomer, separating with preparative high performance liquid chromatography, and collecting cannabidiol monomer with purity of 99% or more.
As a preferred embodiment, the function of the drug is at least one of (1) to (5):
(1) inhibiting apoptosis of cerebral neurons of mice with Parkinson's disease;
(2) reducing the level of inflammatory factor TNF-alpha;
(3) reducing the level of inflammatory factor IL-1 β;
(4) reducing the level of inflammatory factor IL-6;
(5) preventing the oxidative stress of the organism and reducing the oxidative stress level.
The invention has the beneficial effects that:
the method adopts MPTP to establish a Parkinson disease mouse model, simultaneously establishes a normal group, a model group, a positive group, a cannabidiol monomer group, a DP189 group and a cannabidiol monomer + DP189 group, respectively performs intragastric administration, continuously performs intragastric administration for 14 days, and discusses the improvement effect of the combined application of a Lactobacillus plantarum (L.plantarum) DP189 strain and a cannabidiol monomer on the Parkinson disease model mouse. Research results show that the combined application of cannabidiol monomer and lactobacillus plantarum (L.plantarum) DP189 strain can improve the ethological ability of a Parkinson disease model mouse; inhibiting apoptosis of cerebral neurons of a Parkinson disease model mouse; reducing inflammatory response, reducing the levels of inflammatory factors TNF-alpha, IL-1 beta and IL-6; preventing the oxidative stress reaction of the Parkinson disease model mouse and reducing the oxidative stress level. Therefore, the cannabidiol monomer and the lactobacillus plantarum DP189 strain provided by the invention can be used for preparing medicines and medicines for resisting Parkinson's disease in a combined application manner, and the application prospect is very wide.
Drawings
FIG. 1 shows the experimental results of the behavioral tests of the mouse model of Parkinson's disease in example 1. In FIG. 1, A is a water maze experiment latency variation diagram of a Parkinson's disease model mouse; in FIG. 1, B is a graph showing the change of the experimental times of the autonomous activity of the mouse model of Parkinson's disease. In the figure, "+" indicates significant difference (P <0.05) and "+" indicates extremely significant difference (P <0.01) compared to the model group.
FIG. 2 shows the results of the detection of cerebral neurotransmitters by the mouse model of Parkinson's disease in example 1. FIG. 2A is a graph showing the change in the 5-hydroxytryptamine (5-HT) levels in the brains of mice in the Parkinson's disease model; in FIG. 2, B is a graph showing the change of Dopamine (DA) content in the brain of a mouse model of Parkinson's disease. In the figure, "+" indicates significant difference (P <0.05) and "+" indicates extremely significant difference (P <0.01) compared to the model group.
Detailed Description
The cannabidiol monomer (CBD) and the lactobacillus plantarum DP189 are combined to prepare the medicine for treating the Parkinson disease.
Preferably, the concentration of cannabidiol monomer (CBD) is 2.4 mg/mL; lactobacillus plantarum DP189 at a concentration of 109～1010CFU/mL; cannabidiol monomers (CBD) andlactobacillus plantarum (l.plantarum) DP189 was used separately.
Preferably, lactobacillus plantarum (l.plantarum) DP189 has been deposited in the chinese collection for type culture collection, CCTCC for short, in 2019 at 25.3.m. with the address: eight-path Wuhan university school (Wuhan university collection center) 299 in Wuchang area, Wuhan city, Hubei province has the collection number: CCTCC NO: and M2019199.
In addition, other information about lactobacillus plantarum DP189 may include separation, identification, preservation, etc. all refer to chinese patent publication No. CN 110066753 a (entitled lactobacillus plantarum DP189 and its applications).
Preferably, Lactobacillus plantarum DP189 is used, suspended in 2% Tween-80 saline at a concentration of 109～1010CFU/mL。
Preferably, cannabidiol monomer (CBD) is used, dissolved in 2% Tween-80 saline at a concentration of 2.4 mg/mL.
Preferably, the cannabidiol monomer (CBD) has a purity of greater than or equal to 99%.
Preferably, the cannabidiol monomer (CBD) is prepared by the following method:
selecting fresh industrial hemp leaves, and air-drying; weighing air-dried industrial hemp flower leaves, adding 20 times of food-grade 95% ethanol, heating, refluxing and extracting for two times, filtering, combining filtrates, and recovering solvent under reduced pressure to obtain extract containing cannabidiol monomer; adding the extract into ethyl acetate according to the weight ratio of the extract to the ethyl acetate of 1:10, and extracting with water; standing overnight, removing water layer, recovering ethyl acetate layer under reduced pressure to obtain cannabinol crude product containing cannabidiol monomer, separating with preparative high performance liquid chromatography, and collecting cannabidiol monomer with purity of 99% or more.
Preferably, the function of the drug is at least one of (1) to (5):
(1) inhibiting apoptosis of cerebral neurons of mice with Parkinson's disease;
(2) reducing the level of inflammatory factor TNF-alpha;
(3) reducing the level of inflammatory factor IL-1 β;
(4) reducing the level of inflammatory factor IL-6;
(5) preventing the oxidative stress of the organism and reducing the oxidative stress level.
The ethological ability of the Parkinson disease mouse can be improved by taking Lactobacillus plantarum DP189 and cannabidiol monomers in daily time intervals, namely, not simultaneously taking the L.planterum DP189 and cannabidiol monomers to replace the medicine for treating the Parkinson disease; inhibiting apoptosis of cerebral neurons of mice with Parkinson's disease; reducing inflammatory response, reducing the levels of inflammatory factors TNF-alpha, IL-1 beta and IL-6; preventing the oxidative stress of the organism and reducing the oxidative stress level. Has good preventing and treating effects on the Parkinson's disease, and is safe and free from toxic and side effects.
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The test materials used in the following examples were purchased from conventional biochemicals, unless otherwise specified. The quantitative tests in the following examples, all set up three replicates and the results averaged.
Experimental materials:
liquid MRS medium: the solvent is water, and contains peptone 10g/L, beef extract 10g/L, and yeast extract 5g/L, KH2PO42g/L, sodium acetate 5g/L, sodium citrate 5g/L, MgSO4·7H2O 0.2g/L、MnSO4·4H2O0.05 g/L, Tween-801 mL/L and glucose 20 g/L; the pH was 6.6.
C57BL/6 mice (weight 18-22 g): purchased from the enchanter national ministry of animal technology, billions, Catharanthus roseus.
Basic feed: purchased from the enchanter national ministry of animal technology, billions, Catharanthus roseus.
Cannabidiol monomer: selecting fresh industrial hemp flower and leaf, air-drying, weighing 500g of air-dried industrial hemp flower and leaf, adding 20 times of food grade ethanol (95%), heating, refluxing and extracting twice, filtering, combining filtrates, and recovering solvent under reduced pressure to obtain extract containing cannabidiol; putting the extract into ethyl acetate according to the weight ratio of the extract to the ethyl acetate of 1:10, and extracting with water; standing overnight, discarding the water layer, recovering ethyl acetate layer under reduced pressure to obtain cannabinol crude product containing cannabidiol, separating cannabidiol with preparative high performance liquid chromatography, and collecting cannabidiol monomer with purity of 99% or more.
Detecting the content of TNF-alpha in serum by adopting a Jiangsu enzyme-labeled mouse tumor necrosis factor (TNF-alpha) ELISA kit; detecting the content of IL-1 beta in serum by adopting a Jiangsu enzyme-labeled mouse interleukin 1 beta (IL-1 beta) ELISA kit; detecting the content of IL-6 in serum by adopting a Jiangsu enzyme-labeled mouse interleukin 6(IL-6) ELISA kit; detecting the content of DA in the substantia nigra of brain by adopting a Jiangsu enzyme-labeled mouse neurotransmitter Dopamine (DA) ELISA kit; 5-HT content in brain substantia nigra is detected by adopting Jiangsu enzyme-labeled mouse neurotransmitter 5-hydroxytryptamine (5-HT) ELISA kit.
MPTP was purchased from sigma, USA, among others.
Example 1 Effect of Lactobacillus plantarum DP189 Strain, cannabidiol monomer, combination of cannabidiol monomer and Lactobacillus plantarum DP189 Strain on Parkinson's disease model mice
First, establishment and grouping of animal models
Healthy male C57BL/6 mice for 8 weeks were selected for the experiment and were injected intraperitoneally with MPTP (30mg/kg) or physiological saline once a day for 7 consecutive days. Injecting apomorphine (5mg/kg) into the abdominal cavity 7 days after MPTP treatment, recording the rotation times within 30 mm, if the mouse rotates leftwards constantly and the rotation circle is more than 7r/min, the model is successfully made, meanwhile, abnormal actions such as hair erection, tremor, front leg lifting, tail erection and the like should appear 5-30 min after the last MPTP treatment, the symptoms are relieved after 0.5-1 h, and the mouse returns to normal after 24 h. Mice with successful models were screened and randomized into 6 groups of gavage (15 per group): the normal group and the model group contain 0.2mL/d of physiological saline of 2 percent of Tween-80 in gavage of 9:00 and 16:00 per day; the positive group is perfused with L-DOPA solution 0.2mL/d at a ratio of 9:00 per day and perfused with physiological saline solution containing 2% Tween-80 at a ratio of 16:00 per day at a ratio of 0.2 mL/d; the cannabidiol monomer group comprises 0.2mL/d of cannabidiol monomer solution for 9:00 intragastric administration and 0.2mL/d of normal saline containing 2% Tween-80 for 16:00 intragastric administration; DP189 group was gavaged at 9: 00/day and 2% Tween-80 saline 0.2mL/d, and gastric DP189 strain at 16: 00/d; the cannabidiol monomer + DP189 group had a 9:00 intragastric cannabidiol monomer solution of 0.2mL/d and a 16:00 intragastric DP189 strain of 0.2mL/d per day. The above groups were administered continuously for 14 d. The assay behavioural experiment started on day 15 and 24h later mice were sacrificed and mouse serum and brain tissue collected for testing.
Behavioral experiment of mouse model with Parkinson's disease
The results of the mouse behavioural experiments are shown in figure 1. The experiment shows that the cannabidiol monomer and the lactobacillus plantarum DP189 strain can independently shorten the water maze latency of a mouse and increase the times of mouse autonomous activity experiments, but the single action of the cannabidiol monomer and the lactobacillus plantarum DP189 strain is weaker than the action of the cannabidiol monomer and the lactobacillus plantarum DP189 strain in combined administration, compared with a model group, the cannabidiol monomer + DP189 group can improve the memory capacity and the behavior capacity of a Parkinson disease model mouse, and has extremely significant difference (P < 0.01).
Detection of mouse brain tissue related indexes in Parkinson's disease model
The main pathological feature of parkinson's disease is the death or loss of dopaminergic neurons in the substantia nigra of the brain, resulting in a reduction of dopamine content in the brain, ultimately leading to morbidity. 5-hydroxytryptamine (5-HT) is a key enzyme in the pathway for synthesizing dopamine in the body, and the content change of the 5-hydroxytryptamine seriously influences the content of dopamine in the collective body. The result of the detection of the mouse brain neurotransmitter by the ELISA kit is shown in figure 2, the cannabidiol monomer + DP189 group can improve the 5-HT content and the DA content in the mouse brain, compared with a model group, the 5-HT content is increased by 17.42 percent, the DA content is increased by 11.25 percent, the effect is obvious compared with that of single medicine application, and the obvious difference is achieved (P is less than 0.01).
Detection of oxidative stress indexes in serum of mouse with Parkinson's disease model
The results of the oxidative stress kit are shown in table 1. The experiment shows that compared with the normal group, the model group mice have lower contents of SOD and GSH-Px, and the ROS content and the MDA level are greatly increased, which shows that the adoption of the MPTP-induced subacute Parkinson disease mouse model is more successful. Compared with a model group, the cannabidiol monomer can increase the content of SOD and GSH-Px in the brain of a mouse, reduce the content of ROS and the level of MDA, and has extremely significant difference (P < 0.01); the lactobacillus plantarum DP189 strain also shows better antioxidant activity and has significant difference (P < 0.05); it is noted that the antioxidant effect of cannabidiol monomer + DP189 group is stronger than that of the two single drug groups (CBD group and DP189 group), wherein the content of SOD is increased by about 41.91% compared with the model group, and the content of ROS is reduced by about 15.13% compared with the model group, which shows good antioxidant activity and has extremely significant difference (P < 0.01).
TABLE 1
Note: compared to the model group, "+" indicates significant difference (P <0.05) and "+" indicates very significant difference (P < 0.01).
Five, detection of inflammatory factor level in serum of Parkinson's disease model mouse
The production of inflammatory factors plays an important role in the pathogenesis of the Parkinson's disease, and the increase of the level of the inflammatory factors can greatly improve the morbidity of the Parkinson's disease. The results of the detection of the levels of inflammatory factors in the serum of the mouse model of Parkinson's disease are shown in Table 2. Experiments show that the level of the inflammatory factors in the bodies of the Parkinson's disease patients is far higher than that of the bodies of the normal patients. The inflammation experiment result shows that the cannabidiol monomer + DP189 group can obviously reduce the contents of TNF-alpha, IL-6 and IL-1 beta inflammatory factors in the serum of a mouse with the Parkinson's disease, the effect of the combined medication of the cannabidiol monomer and the DP189 group is superior to that of the single medication (CBD group and DP189 group), and compared with a model group, the content of TNF-alpha is reduced by 22.25 percent, the content of IL-6 is reduced by 12.61 percent, the content of IL-1 beta is reduced by 14.40 percent, and the obvious difference is realized (P is less than 0.01).
TABLE 2
Note: compared to the model group, "+" indicates significant difference (P <0.05) and "+" indicates very significant difference (P < 0.01).
The invention discloses an application of cannabidiol monomer and lactobacillus plantarum DP189 in preparation of a medicine for preventing and/or treating Parkinson's disease, which can be realized by appropriately improving process parameters by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the invention has been described in terms of preferred embodiments, it will be apparent to those skilled in the art that the technology can be practiced and applied by modifying or appropriately combining the products described herein without departing from the spirit and scope of the invention.
Claims (8)
1. The application of the cannabidiol monomer and the lactobacillus plantarum DP189 in the preparation of the medicine for preventing and/or treating the Parkinson disease.
2. The use of claim 1, wherein the cannabidiol monomer is present at a concentration of 2.4 mg/mL; the concentration of the lactobacillus plantarum DP189 is 109～1010CFU/mL; the cannabidiol monomer is used separately from lactobacillus plantarum DP 189.
3. The use according to claim 1, wherein said Lactobacillus plantarum DP189 has been deposited with the China center for type culture Collection in 2019, 3, 25, under accession number: CCTCC NO: and M2019199.
4. The use according to claim 1, wherein the Lactobacillus plantarum DP189 is used suspended in 2% Tween-80 in normal saline at a concentration of 109～1010CFU/mL。
5. The use of claim 1 wherein cannabidiol monomer, when used, is dissolved in 2% tween-80 saline at a concentration of 2.4 mg/mL.
6. The use of claim 1, wherein the cannabidiol monomer is at least 99% pure.
7. The use of claim 1, wherein the cannabidiol monomer is prepared by:
selecting fresh industrial hemp leaves, and air-drying; weighing air-dried industrial hemp flower leaves, adding 20 times of food-grade 95% ethanol, heating, refluxing and extracting for two times, filtering, combining filtrates, and recovering solvent under reduced pressure to obtain extract containing cannabidiol monomer; adding the extract into ethyl acetate according to the weight ratio of the extract to the ethyl acetate of 1:10, and extracting with water; standing overnight, removing water layer, recovering ethyl acetate layer under reduced pressure to obtain cannabinol crude product containing cannabidiol monomer, separating with preparative high performance liquid chromatography, and collecting cannabidiol monomer with purity of 99% or more.
8. The use according to claim 1, wherein the function of the drug is at least one of (1) to (5):
(1) inhibiting apoptosis of cerebral neurons of mice with Parkinson's disease;
(2) reducing the level of inflammatory factor TNF-alpha;
(3) reducing the level of inflammatory factor IL-1 β;
(4) reducing the level of inflammatory factor IL-6;
(5) preventing the oxidative stress of the organism and reducing the oxidative stress level.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110647548.5A CN113288920B (en) | 2021-06-10 | 2021-06-10 | Application of cannabidiol monomer and lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Parkinson's disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110647548.5A CN113288920B (en) | 2021-06-10 | 2021-06-10 | Application of cannabidiol monomer and lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Parkinson's disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113288920A true CN113288920A (en) | 2021-08-24 |
| CN113288920B CN113288920B (en) | 2023-03-28 |
Family
ID=77327929
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110647548.5A Active CN113288920B (en) | 2021-06-10 | 2021-06-10 | Application of cannabidiol monomer and lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Parkinson's disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113288920B (en) |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014141265A1 (en) * | 2013-03-14 | 2014-09-18 | Nofar Gil | Inhibition of neurodegenerative disease by grape seed extract, green tea extract and probiotic bacteria |
| WO2018114783A1 (en) * | 2016-12-23 | 2018-06-28 | Bayer Pharma Aktiengesellschaft | Tetrazole containing compounds |
| CN108603162A (en) * | 2015-09-15 | 2018-09-28 | 庆熙大学校产学协力团 | Prevention, the novel lactic acid bacteria and composition for improving or treating degenerative brain disorder or cognition dysfunction |
| CN110066753A (en) * | 2019-05-13 | 2019-07-30 | 吉林省农业科学院 | Lactobacillus plantarum DP189 and its application |
| US20190246591A1 (en) * | 2017-05-31 | 2019-08-15 | Insectergy, Llc | Insect and cannabis production systems and methods |
| WO2019157585A1 (en) * | 2018-02-13 | 2019-08-22 | Proviva Pharma Inc. | Probiotic formulations for the treatment and alleviation of metabolic and oxidative stress, inflammation and neurodegeneration |
| CN110637093A (en) * | 2017-05-18 | 2019-12-31 | 株式会社益力多本社 | Marker and method for determining Parkinson's disease |
| CN110891430A (en) * | 2017-06-19 | 2020-03-17 | 波比奥泰克股份公司 | Composition comprising a bacterial strain belonging to the species lactobacillus salivarius for the treatment of parkinson's disease |
| CN110964665A (en) * | 2019-12-20 | 2020-04-07 | 哈尔滨美华生物技术股份有限公司 | Probiotic composition for post-gastrectomy treatment and preparation method thereof |
| CN112915109A (en) * | 2021-01-21 | 2021-06-08 | 吉林省农业科学院 | Application of lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Alzheimer disease |
| WO2021156777A1 (en) * | 2020-02-06 | 2021-08-12 | Buzzelet Development And Technologies Ltd. | Microbial combinations and uses thereof |
| WO2022213931A1 (en) * | 2021-04-06 | 2022-10-13 | 山东绿叶制药有限公司 | Prodrug of cannabidiol, and pharmaceutical composition and use thereof |
-
2021
- 2021-06-10 CN CN202110647548.5A patent/CN113288920B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014141265A1 (en) * | 2013-03-14 | 2014-09-18 | Nofar Gil | Inhibition of neurodegenerative disease by grape seed extract, green tea extract and probiotic bacteria |
| CN108603162A (en) * | 2015-09-15 | 2018-09-28 | 庆熙大学校产学协力团 | Prevention, the novel lactic acid bacteria and composition for improving or treating degenerative brain disorder or cognition dysfunction |
| WO2018114783A1 (en) * | 2016-12-23 | 2018-06-28 | Bayer Pharma Aktiengesellschaft | Tetrazole containing compounds |
| CN110637093A (en) * | 2017-05-18 | 2019-12-31 | 株式会社益力多本社 | Marker and method for determining Parkinson's disease |
| US20190246591A1 (en) * | 2017-05-31 | 2019-08-15 | Insectergy, Llc | Insect and cannabis production systems and methods |
| CN110891430A (en) * | 2017-06-19 | 2020-03-17 | 波比奥泰克股份公司 | Composition comprising a bacterial strain belonging to the species lactobacillus salivarius for the treatment of parkinson's disease |
| WO2019157585A1 (en) * | 2018-02-13 | 2019-08-22 | Proviva Pharma Inc. | Probiotic formulations for the treatment and alleviation of metabolic and oxidative stress, inflammation and neurodegeneration |
| CN110066753A (en) * | 2019-05-13 | 2019-07-30 | 吉林省农业科学院 | Lactobacillus plantarum DP189 and its application |
| CN110964665A (en) * | 2019-12-20 | 2020-04-07 | 哈尔滨美华生物技术股份有限公司 | Probiotic composition for post-gastrectomy treatment and preparation method thereof |
| WO2021156777A1 (en) * | 2020-02-06 | 2021-08-12 | Buzzelet Development And Technologies Ltd. | Microbial combinations and uses thereof |
| CN112915109A (en) * | 2021-01-21 | 2021-06-08 | 吉林省农业科学院 | Application of lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Alzheimer disease |
| WO2022213931A1 (en) * | 2021-04-06 | 2022-10-13 | 山东绿叶制药有限公司 | Prodrug of cannabidiol, and pharmaceutical composition and use thereof |
Non-Patent Citations (3)
| Title |
|---|
| LEI WANG等: "Lactobacillus plantarum DP189 reduces α-SYN aggravation in MPTP-induced parkinson’s disease mice via regulating oxidative damage,inflammation, and gut microbiota disorder", 《L AGRIC FOOD CHEM》 * |
| 何忠梅等: "植物乳杆菌Sc52对脂多糖诱导小鼠肠道屏障损伤的保护作用", 《食品科学》 * |
| 林悄然等: "复合乳酸菌治疗帕金森病便秘的6例报道", 《中国神经免疫学和神经病学杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113288920B (en) | 2023-03-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110604749B (en) | Bifidobacterium animalis A12 and its application in controlling diabetes or hyperlipidemia, especially weight gain or obesity | |
| CN101301310B (en) | Use of brown alga polysaccharide sulfate in preventing and treating Parkinson's disease | |
| CN111040044B (en) | Cordyceps militaris intracellular polysaccharide, preparation method and application thereof in regulating intestinal flora | |
| CN112915109B (en) | Application of lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Alzheimer disease | |
| CN102070695B (en) | Preparation and application of ergosterin derivative | |
| CN107496435B (en) | Application of Anoectochilus formosanus glycoside in preparation of anti-fatigue medicine | |
| CN114717147A (en) | Metazoan prepared from Lactobacillus rhamnosus and used for relieving fatty liver and obesity, and application thereof | |
| CN104922176B (en) | A kind of application of Flos Chrysanthemi Indici extract | |
| CN115109734B (en) | Lactobacillus agilis B13T4 with function of relieving hyperuricemia and application thereof | |
| CN110777098A (en) | Lactobacillus with effect of preventing and treating diabetic encephalopathy and separation method and application thereof | |
| CN112351692A (en) | Composition for improving liver function comprising leuconostoc strain | |
| CN115887483A (en) | Application of lactobacillus fermentum CECT5716 exopolysaccharide in preparation of medicines for preventing or improving chronic kidney diseases | |
| CN111329884A (en) | Application of lactobacillus plantarum BC299 in medicines and foods for treating inflammatory bowel diseases and psychogenic problems | |
| KR101614929B1 (en) | A pharmaceutical composition for treating cognitive and memory impairment | |
| CN113717883B (en) | Lactobacillus plantarum FLPL05 for promoting body health and longevity and application thereof | |
| CN113288920B (en) | Application of cannabidiol monomer and lactobacillus plantarum DP189 in preparation of medicine for preventing and/or treating Parkinson's disease | |
| CN114680331A (en) | Food composition, pharmaceutical composition, quasi-pharmaceutical composition, feed composition and preparation method thereof | |
| CN113337428A (en) | Lactobacillus plantarum HNU082 and application thereof | |
| WO2005077390A1 (en) | Hypoglycemic agent, remedy/preventive for diabetes and proces for producing the same | |
| KR100972167B1 (en) | Composition for antioxidation and preventing or treating immune disease comprising Alaria esculenta extract as an active ingredient | |
| CN115191607A (en) | Lactobacillus plantarum YU28 strain and application thereof | |
| CN110343189A (en) | Durian peel polysaccharide, extracting method and its application in terms of preparation adjusts intestinal flora and/or treats functional consitipation drug | |
| CN114524739B (en) | Separation method and application of diaminocitric acid in green plum enzyme | |
| CN114292343B (en) | Preparation method of perennial cerasus extracellular polysaccharide and intracellular polysaccharide and application of perennial cerasus extracellular polysaccharide and intracellular polysaccharide in regulating intestinal microbial flora and reducing blood sugar | |
| CN112755055B (en) | Application of lactobacillus plantarum NA136 and cannabidiol monomer combination in preparation of product for treating rheumatoid arthritis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |