CN114392260A - Medicine for relieving anxiety and depression - Google Patents

Medicine for relieving anxiety and depression Download PDF

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Publication number
CN114392260A
CN114392260A CN202210135820.6A CN202210135820A CN114392260A CN 114392260 A CN114392260 A CN 114392260A CN 202210135820 A CN202210135820 A CN 202210135820A CN 114392260 A CN114392260 A CN 114392260A
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Prior art keywords
extract
acid
chloroform
ethyl acetate
methyl
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CN202210135820.6A
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Inventor
庞金宇
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Chongqing Jiulongpo District Mental Health Center Chongqing Jiulongpo District Shipingqiao Hospital
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Chongqing Jiulongpo District Mental Health Center Chongqing Jiulongpo District Shipingqiao Hospital
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Priority to CN202210135820.6A priority Critical patent/CN114392260A/en
Publication of CN114392260A publication Critical patent/CN114392260A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/4748Quinolines; Isoquinolines forming part of bridged ring systems
    • 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
    • A61K36/11Pteridophyta or Filicophyta (ferns)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • 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
    • 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
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

Abstract

The invention discloses application of a lycopodium clavatum extract in preparing a medicament for relieving anxiety and depression and a preparation method thereof.

Description

Medicine for relieving anxiety and depression
Technical Field
The invention belongs to the technical field of traditional Chinese medicine extracts, and relates to a traditional Chinese medicine extract for relieving anxiety and depression.
Background
Depression and anxiety disorder are common mental disorder psychological diseases, have the characteristics of high morbidity, high disability rate and high recurrence rate, and seriously affect human health, and the current clinical common antidepressant mainly takes western medicines such as imipramine, flupentixol melitracen tablets, novel antidepressant anxiety drug paroxetine hydrochloride and the like, but has the problems of more contraindications, large addiction, obvious side effect, easy recurrence after drug withdrawal, lower effective rate, poorer patient compliance and the like.
Depression and anxiety disorder belong to the category of depression in traditional Chinese medicine, and are mostly caused by qi stagnation, qi and blood dysfunction of viscera and imbalance of yin and yang due to emotional failure. In the treatment and rehabilitation and nursing processes of anxiety and depression, the traditional Chinese medicine has the advantages of multiple targets, multiple ways, multiple levels and multiple mechanisms. In recent years, various traditional Chinese medicines such as liquorice, albizia flower, fructus psoraleae, radix puerariae, coptis chinensis and the like are reported to have the effects of relieving anxiety and depression, the effective components comprise flavonoids, terpenes, phenylpropanoids, quinones, alkaloids and the like, and the effects are shown in various aspects such as the regulation of monoamine neurotransmitter biochemical abnormality, the regulation of the internal environment of an organism, the energy metabolism function and the like.
Caulis et folium Pothi Repentis (Lycopodiastrum casuarinioides (Spring) Holub ex Dixi) is a fern of Lycopodiaceae, and is also called "Shujincao" for relieving rigidity of muscles and promoting blood circulation, and can be used for treating rheumatic arthralgia, traumatic injury, arthralgia and myalgia, menoxenia and foot spasm. Mainly contains Lycodine type lycopine alkaloid, can resist bacteria, tumors, oxidation, blood sugar and inflammation, and has good acetylcholinesterase resisting activity. At present, no report is found on the effect of the traditional Chinese medicine for relieving anxiety and depression.
The invention further discovers that the lycopodium clavatum extract has the functions of relieving anxiety and depression, so the invention further discovers the potential of the lycopodium clavatum extract on treating new indications.
Disclosure of Invention
The invention aims to provide a medicine for relieving anxiety and depression, which mainly comprises the active ingredient of the whole plant extract of the lycopodium clavatum, and the specific technical scheme is as follows: a medicine for relieving anxiety and depression comprises an ethanol and/or methanol extract of Pinus sylvestris which is rich in alkaloid, has nerve cell protection function and acetylcholinesterase resisting activity, and can relieve anxiety and depression.
According to some embodiments of the invention, the method of preparing the lycopodium giganteum extract comprises the steps of: cleaning whole plant of herba Lycopodii Serrati, sun drying, weighing, pulverizing, extracting, filtering, drying to obtain extract, selecting ethanol and/or methanol as extraction solvent, collecting extractive solution, filtering, concentrating to obtain whole extract, extracting with different solvents, concentrating to obtain extract, and drying.
Detailed Description
In order to explain the technical content, the objects and the effects of the present invention in detail, the following description will be given with reference to the embodiments.
The test methods used in the examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are commercially available reagents and materials unless otherwise specified.
Example 1:
a preparation method of a medicine for relieving anxiety and depression comprises pulverizing dried whole plant of radix et rhizoma Boussingaultiae Pseudochinensis 20kg, extracting with ethanol under reflux, filtering, and concentrating to obtain extract.
Further, adding tartaric acid aqueous solution and ethyl acetate into the extract for extraction, adjusting the pH value of a water phase, extracting with chloroform, and concentrating the extract to obtain the extract.
The method comprises the following specific steps: collecting dried herba Lycopodii Serrati 20kg, pulverizing, reflux extracting with 120L 70-90% ethanol for 3 times, each time for 2 hr, at 70-85 deg.C, and concentrating the extractive solution to obtain fluid extract 1.8 kg. Adding 3% tartaric acid water solution and ethyl acetate into the fluid extract, suspending to 20L, adding saturated Na into the water phase2CO3After adjusting the pH to 10, chloroform extraction was further performed to obtain an ethyl acetate extract (238 g) and a chloroform extract (60 g). And determining the main extraction components by silica gel column chromatography, polyamide column chromatography, HPLC semi-preparative chromatography and other separation means at the later stage.
An 80% ethanol solution is preferred as the extraction solvent.
Example 2:
a preparation method of a medicine for relieving anxiety and depression comprises collecting dried whole plant of radix et rhizoma Boussingaultiae Pseudobaselloidis 20kg, pulverizing, adding methanol, extracting under hot reflux, filtering, and concentrating to obtain extract.
Further, adding tartaric acid aqueous solution and ethyl acetate into the extract for extraction, adjusting the pH value of a water phase, extracting with chloroform, and concentrating the extract to obtain the extract.
The method comprises the following specific steps: collecting 20kg of dried whole plant of Pinus sylvestris, extracting with 120L 70-85% methanol under reflux for 3 times, each time for 2 hr, at 70-85 deg.C, and concentrating the extractive solution to obtain 2kg of total fluid extract. Adding 3% tartaric acid water solution and ethyl acetate into the fluid extract, suspending to 25L, adding saturated Na into the water phase2CO3After adjusting the pH to 10, chloroform extraction was further performed to obtain an ethyl acetate extract (256 g) and a chloroform extract (70 g). And determining the main extraction components by silica gel column chromatography, polyamide column chromatography, HPLC semi-preparative chromatography and other separation means at the later stage.
A75% methanol solution is preferred as the extraction solvent.
In order to make the technical means, technical features, objectives and effects achieved by the present invention easily understandable, the following experiments or experimental studies are used to further illustrate the present invention.
Experimental animals and groups
50 healthy Kunming mice with the weight of 20-25g and male sex are selected. After being fed for 1 week in a conventional adaptive manner, the animals were randomly divided into a model group, a positive control group (imipramine, dosage 20.0 mg/kg), a total fluid extract (A) group (dosage 200 mg/kg), an ethyl acetate (B) group (dosage 200 mg/kg) and a chloroform (C) group (dosage 200 mg/kg) according to body weight.
Tail suspension experiment
The 2cm part of the tail end of the mouse is attached to a horizontal stick, so that the animal is in an inverted hanging state, the head of the mouse is about 8cm away from the table surface, no place for the mouse to climb is arranged around the table surface, the two sides of the suspension are separated from the sight of the animal by baffles so as to prevent mutual interference, and the floating and motionless time of each animal within 6min after 4min is recorded. The tail-suspended mouse struggles to move for overcoming abnormal body positions, but after moving for a certain time, the tail-suspended mouse appears discontinuous immobility, and displays an 'despair' state.
Forced swimming experiment
Each group of mice is continuously administrated for 14 days, and after the last administration for 1h, each group of mice is independently put into a water tank (40 cm in height and 18cm in diameter) with the water depth of 15cm, the water temperature is 25 +/-1 ℃, the mice are adapted for 2min, then are forcedly swim for 6min, and the floating and motionless time of each mouse is observed and recorded within 6min and 4min later.
Results of the experiment
TABLE 1 Effect of the herbal extracts of the present invention on the time to keep the mice afloat and still for forced swimming
Figure DEST_PATH_IMAGE002
As a result: compared with the model group, the full-fluid extract A group, the ethyl acetate B group and the chloroform C group obviously shorten the time for keeping the tail suspended to float and the time for keeping the tail suspended to float in forced swimming, wherein the chloroform C group has the most obvious effect.
And (4) conclusion: the extract of Pinus sylvestris can effectively relieve anxiety and depression.
After later-stage identification:
ethyl acetate layer extraction ingredients: furfural (furfurfuraldehyde), monomethyl fumarate (monomethylfumarate), methyl dihydroferulic acid (dihydroferulic acid methyl ester), ethyl dihydroferulic acid (dihydroferulic acid ethyl ester), ethyl caffeate (caffeic acid ethyl ester), 5, 7-dihydroxy-2-methylchromone (5, 7-dihydroxy-2-methyl chloride), abscisic acid (abscisic acid), ethyl nervonate (ethyl orsellinate), 4-methoxybenzoic acid (4-methoxybenzoic acid), vanillic acid (vanillic acid).
Chloroform layer extraction of components: lycoserramine-M N-oxide, acetyl-lycoserramine-M, lycopodine (lycopodine), lycoserramine-M, miyoshinine C, 12-epoxydoline N-oxide, gnidiiodine, lycoserramine-K, lucidiline (lucidiline), 4 alpha-hydroxyyanhydroxodiol, flubelline; hydroxypyrodine, lycopodine (lycodine), des-N-methyl-alpha-phellodendrine (des-N-methyl-alpha-obstrurine), alpha-phellodendrine (alpha-obstrurine), des-N-methyl-beta-phellodendrine (des-N-methyl-beta-obstrurine), lycopodrine (lycoflexine), lycoflexidine N-oxide, fabridine (facettidine), N-oxideopine M.
The foregoing describes preferred embodiments of the present invention, but is not intended to limit the invention thereto. Modifications and variations of the embodiments disclosed herein may be made by those skilled in the art without departing from the scope and spirit of the invention.

Claims (10)

  1. The application of the Lycodine alkaloid in preparing the medicines for relieving anxiety and depression has the following main mother ring structure:
    Figure 328117DEST_PATH_IMAGE001
    and
    Figure 294805DEST_PATH_IMAGE002
    R1= OH、OCH3、H
    R2=CH3、H
    R3= H、CH2OH、OH。
  2. 2. an application of the extract of the lycopodine in preparing the medicines for relieving anxiety and depression, wherein the main effective component of the extract is the Lycodine alkaloid in the claim 1.
  3. 3. The use of claim 1, wherein the extract solvent is methanol and/or ethanol, and the extract is obtained by extracting with ethyl acetate, tartaric acid water, and chloroform.
  4. 4. The use of claim 3, wherein the extract is an ethyl acetate extract.
  5. 5. The use of claim 3, wherein the extract is a chloroform extract.
  6. 6. The method for preparing the extract as claimed in any one of claims 2 to 5, wherein the extraction solvent is ethanol, dried whole plant of Pinus sylvestris 20kg is taken, pulverized, extracted with 120L 70-90% ethanol under reflux for 3 times at 70-85 deg.C for 2h each time, the extract is concentrated to 1.8kg of total fluid extract, the fluid extract is added with 3% tartaric acid aqueous solution and ethyl acetate and suspended to 20L, and the lower aqueous phase is saturated Na2CO3After adjusting the pH to 10, chloroform was added thereto to extract, thereby obtaining an ethyl acetate extract and a chloroform extract.
  7. 7. The method for preparing the extract as claimed in any one of claims 2-5, wherein the extraction solvent is methanol, dried whole plant of Lycopodium clavatum is 20kg, pulverized, extracted with 120L 70-85% methanol under reflux for 3 times (2 hr each time at 70-85 deg.C), the extractive solution is concentrated into 2kg of total fluid extract,
    adding 3% tartaric acid water solution and ethyl acetate into the fluid extractThe ester was suspended to 25L and the aqueous phase was replaced with saturated Na2CO3After adjusting the pH to 10, chloroform was added thereto to extract, thereby obtaining an ethyl acetate extract and a chloroform extract.
  8. 8. The ethyl acetate extract of claim 4, wherein the main effective ingredients are: furfural (furfurfuraldehyde), monomethyl fumarate (monomethylfumarate), methyl dihydroferulic acid (dihydroferulic acid methyl ester), ethyl dihydroferulic acid (dihydroferulic acid ethyl ester), ethyl caffeate (caffeic acid ethyl ester), 5, 7-dihydroxy-2-methylchromone (5, 7-dihydroxy-2-methyl chloride), abscisic acid (abscisic acid), ethyl nervonate (ethyl orsellinate), 4-methoxybenzoic acid (4-methoxybenzoic acid), vanillic acid (vanillic acid).
  9. 9. The chloroform extract of the extract according to claim 5, which comprises the following main effective components: lycoserramine-M N-oxide, acetyl-lycoserramine-M, lycopodine (lycopodine), lycoserramine-M, miyoshinine C, 12-epoxydoline N-oxide, gnidiiodine, lycoserramine-K, lucidiline (lucidiline), 4 alpha-hydroxyyanhydroxodiol, flubelline; hydroxypyrodine, lycopodine (lycodine), des-N-methyl-alpha-phellodendrine (des-N-methyl-alpha-obstrurine), alpha-phellodendrine (alpha-obstrurine), des-N-methyl-beta-phellodendrine (des-N-methyl-beta-obstrurine), lycopodrine (lycoflexine), lycoflexidine N-oxide, fabridine (facettidine), N-oxideopine M.
  10. 10. Extract for use according to claims 2-9, in the form of a pharmaceutical preparation, in the form of an oral preparation selected from the group consisting of tablets, powders, oral liquids, capsules, granules and syrups.
CN202210135820.6A 2022-02-15 2022-02-15 Medicine for relieving anxiety and depression Pending CN114392260A (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103372174A (en) * 2012-04-27 2013-10-30 王宇红 Compound traditional Chinese medicine for treating depression
CN103980198A (en) * 2013-02-08 2014-08-13 复旦大学 Alkaloid Casuarinine H and use thereof in preparation of medicines for treating neurodegenerative diseases
CN104490972A (en) * 2015-01-06 2015-04-08 山西大学 Pharmaceutical composition for treating and preventing depression and preparation method of pharmaceutical composition
CN104771451A (en) * 2015-04-24 2015-07-15 中国人民解放军第二军医大学 Traditional Chinese medicine extract with antidepressant effect and application thereof
CN105943618A (en) * 2016-06-14 2016-09-21 云南瑞酚生物科技有限公司 Drug for treating depression
CN110251543A (en) * 2019-07-29 2019-09-20 珠海俊一健生物医药科技有限公司 Become application of the leaf tree conopsea extraction in preparation antidepression natural drug

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103372174A (en) * 2012-04-27 2013-10-30 王宇红 Compound traditional Chinese medicine for treating depression
CN103980198A (en) * 2013-02-08 2014-08-13 复旦大学 Alkaloid Casuarinine H and use thereof in preparation of medicines for treating neurodegenerative diseases
CN104490972A (en) * 2015-01-06 2015-04-08 山西大学 Pharmaceutical composition for treating and preventing depression and preparation method of pharmaceutical composition
CN104771451A (en) * 2015-04-24 2015-07-15 中国人民解放军第二军医大学 Traditional Chinese medicine extract with antidepressant effect and application thereof
CN105943618A (en) * 2016-06-14 2016-09-21 云南瑞酚生物科技有限公司 Drug for treating depression
CN110251543A (en) * 2019-07-29 2019-09-20 珠海俊一健生物医药科技有限公司 Become application of the leaf tree conopsea extraction in preparation antidepression natural drug

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DONGKE MA,ET AL: ""Pharmacokinetic Studies of Three Alkaloids in Rats After Intragastrical Administration of Lycopodii Herba Extract by LC-MS/MS"", 《MOLECULES》, vol. 24, pages 297 - 12 *
张东博: ""四种药用植物中生物碱类化学成分的结构及生物活性研究"", 《中国优秀硕士学位论文数据库医药卫生科技辑》, pages 076 - 099 *

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Application publication date: 20220426