CN106138117A - Ganoderma spore oil application in preparing prevention and cure of cardiovascular disease medicine - Google Patents

Ganoderma spore oil application in preparing prevention and cure of cardiovascular disease medicine Download PDF

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Publication number
CN106138117A
CN106138117A CN201610630693.1A CN201610630693A CN106138117A CN 106138117 A CN106138117 A CN 106138117A CN 201610630693 A CN201610630693 A CN 201610630693A CN 106138117 A CN106138117 A CN 106138117A
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ganoderma spore
extraction
ganoderma
cardiovascular disease
oil
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谢意珍
杨柏华
焦春伟
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Guangzhou Pulisen Biotechnology Co Ltd
Guangdong Yuewei Edible Mushroom Technology Co Ltd
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Guangzhou Pulisen Biotechnology Co Ltd
Guangdong Yuewei Edible Mushroom Technology 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
    • A61K36/06Fungi, e.g. yeasts
    • A61K36/07Basidiomycota, e.g. Cryptococcus
    • A61K36/074Ganoderma
    • 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
    • A61K2236/10Preparation or pretreatment of starting material
    • A61K2236/17Preparation or pretreatment of starting material involving drying, e.g. sun-drying or wilting
    • 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
    • A61K2236/35Extraction with lipophilic solvents, e.g. Hexane or petrol ether
    • 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
    • A61K2236/37Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Mycology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The present invention provides the application in preparing prevention and cure of cardiovascular disease medicine of a kind of Ganoderma spore oil.Have employed hypertensive heart disease model caused by ligation left coronary artery, using systole and relaxing period left room chamber wall thickness, internal diameter data, Left Ventricular Ejection Fraction etc. as observation index, its cardiac function is analyzed, result shows, the active component Ganoderma spore oil of separation is extracted in the case of effective dose 3g/ (kg BW) from Ganoderma spore, can improve cardiac function, ejection fraction reaches 66.02, close to blank group numerical value;Painstaking effort output also has preferably improvement, the especially vasodilation abilities of left ventricle to have substantially change, illustrates that Ganoderma spore oil has the effect of prevention cardiovascular disease, can be used for preparing the medicine of prevention and cure of cardiovascular disease.

Description

Ganoderma spore oil application in preparing prevention and cure of cardiovascular disease medicine
[technical field]
The invention belongs to medicines and health protection field, be specifically related to Ganoderma spore oil in preparation prevention cardiovascular disease medicine Application.
[background technology]
The whole world has 16,600,000 people to die from cardiovascular disease every year, and World Health Organization (WHO) estimates: to the year two thousand twenty, this numeral To increase to 25,000,000, the year two thousand twenty cardiovascular disease will become first cause of the death in the world, increasing sharply of cardiovascular patient, Not only increase the chance of anergy and disability, cause huge lost work, also accelerate on medical diagnosis on disease, medical expense Rise, only from the point of view of China, 2003, Zhai Yi etc. to China 35-74 year the hypertension of people, coronary heart disease and the financial burden of apoplexy Study, show that Direct economic burden is respectively as follows: 201.5 hundred million, 157.9 hundred million and 242.97 hundred million yuans, hypertension lead The coronary heart disease caused and the Direct economic burden of apoplexy reach 190.84 hundred million yuans, account for the direct Disease Spectrum of both diseases 47.7%, bring the most painful and serious economic loss to sufferers themselves, family and society, increase family and society Financial burden.At present, medical technique level improves constantly, and various kinds of drug emerges in multitude, and Western medicine is at treatment cardiovascular disease tool There is rapid-action advantage, but there is also simultaneously and need the shortcoming and defect such as Long-term taking medicine, side effect are big, clinically, to treating Exploration discovery in journey, Chinese herbal medicine can overcome the disadvantages that the deficiency of western medicine in treatment cardiovascular disease, and has single drug The advantage obtaining more preferable curative effect, along with research deepens continuously, adds the continuous understanding to Effective Component of Chinese Medicine, the Chinese herbal treatment heart Angiopathy is more and more accepted by patient and medical worker, and has certain superiority.
Ganoderma Ganoderma lucidum (Leyss.ex.Fr.) Karst is the high medicinal fungi that China is famous, as Medicine has the history of more than 2000 year (Lin Zhibin, 2001), and the whole life cycle of Ganoderma includes: Ganoderma mycelium, Ganoderma spore Son and Ganoderma sporophore, but three has significant difference in chemical composition, shows in (2016) research reports such as Hua Zheng: Ganoderma Sporophore, mycelium and spore powder not only polyoses content differs greatly, and lucidum mycelium polysaccharide content reaches 3.81%, and spore powder is many Sugar content is 1.8%, and in Ganoderma sporophore, polyoses content is only 0.59%, and also has the biggest difference at the composition of polysaccharide, passes through HPLC analyzes and finds that contained by these 3 kinds of materials, the kind of polysaccharide is the most inconsistent, and its on-link mode (OLM) of enzymolysis is the most inconsistent;Chen Junhui etc. grind Study carefully report: Ganoderma sporophore becomes containing triterpeness such as abundant Ganodenic acid, clever red acid, Ganoderma lucidum (Leyss. Ex Fr.) Karst. acid methyl ester, Ganoderma spore lactones Point, the peak majority before retention time 50min is Ganodenic acid compounds, relative with Ganoderma spore powder, contains in Ganoderma sporophore There is the content of triterpenoids substantially high than in spore powder.Ganoderma spore is to eject from cap the Ganoderma growth and maturity phase Carry out ultrafine spore, for the sexual cell of Ganoderma, there are whole genetic activities materials of Ganoderma, after extraction, obtain Ganoderma The research quantitative analysis results such as spore oil is the lipid active component of Ganoderma spore, Chen Tiqiang show: detect 9 in Ganoderma spore oil Kind always fatty acid, unsaturated fatty acid total amount is 73.6%, wherein oleic acid, linoleic acid equal size be respectively 57.5%, 13.4%, the most a small amount of hexadecenoic acid, linolenic acid and 19.6% satisfied fatty acid Palmic acid.
Ganoderma extract has cardiotonic, function of resisting myocardial ischemia, and proves that latter effect increases coronary flow with it And cardiac muscle nutritional blood flow, improving Myocardial Microcirculation, increase myocardial oxygen delivery relevant, Lin Zhibin etc. is studied and is found: Ganoderma is real Body triterpene substance can suppress the lipid peroxidation of vascular smooth muscle cell;1986, Morigiwa etc. reported from red sesame 70% ethanol extraction in isolated 8 kinds of Ganoderma triterpenoidss have vitro inhibition Ren sus domestica angiotensin converting enzyme (ACE) live Property effect, and the high activity of ACE be hypertension morbidity key factor, therefore conclude that Ganoderma triterpenoids is likely to be of internal fall Hypotension effect;Triterpene substance hypotensive activity in Ganoderma sporophore is entered by the report according to Morigiwa such as Liu Dong in 2007 Row research, find: dosage respectively when 450mg/kg and 900mg/kg, from Ganoderma sporophore extract triterpene substance SHR rat had obvious hypotensive effect;Yang Hongmei etc. find: 1% ganoderan can be obviously improved hemorrhagic shock and fill The cardiac function of note rabbit;Xue Hua etc. are administered T2DM rat with ganoderma lucidum fruitbody polysaccharide and find for 16 weeks: ganoderma lucidum fruitbody polysaccharide can drop Low blood glucose level and the hemodynamic parameter of T2DM rat can be obviously improved, reduce its oxidative stress level;And patent (CN1365816) preventing and treating cardiovascular disease health medicine containing ganoderic oligose and preparation method thereof is announced.
In sum, though Ganoderma spore and sporophore are the important growth stage of Ganoderma life cycle, but Ganoderma sporophore and spirit Ganoderma lucidum spore has significant difference in chemical composition kind and content, and the fat-soluble active ingredient of Ganoderma sporophore concentrates on total three On terpene, its polyoses content is low, and monosaccharide is mainly glucose and galactose;And the fat-soluble active ingredient of Ganoderma spore concentrates on not On satisfied fatty acid, its polyoses content is high, and monosaccharide is mainly glucose.Up to now, cardiovascular disease is improved about Ganoderma Report all concentrates on triterpene substance and the polysaccharose substance of Ganoderma sporophore extraction, and about Ganoderma spore and Ganoderma spore There is not been reported in the research improving cardiovascular function for oil.
[summary of the invention]
For above-mentioned situation, it is an object of the invention to provide a kind of Ganoderma spore oil and preparing prevention and cure of cardiovascular disease medicine In application.Present invention employs hypertensive heart disease model caused by ligation left coronary artery, left with systole and relaxing period Its cardiac function, as observation index, is analyzed by room chamber wall thickness, internal diameter data, Left Ventricular Ejection Fraction etc., and result shows, from Ganoderma spore extracts the active component Ganoderma spore oil of separation in the case of effective dose 3g/ (kg BW), heart can be improved Function, ejection fraction reaches 66.02, close to blank group numerical value;Painstaking effort output also has preferably improvement, especially left ventricle Vasodilation abilities have substantially change.Illustrate that Ganoderma spore oil has the effect of prevention cardiovascular disease, can be used for the preparation preventing and treating heart The medicine of angiopathy.
In above-mentioned application, described Ganoderma spore oil can pass through soxhlet extraction method, supercritical CO2Extraction, microwave extraction A kind of acquisition in method and ultrasonic extraction.
Described soxhlet extraction method obtains concretely comprising the following steps of Ganoderma spore oil: Ganoderma spore powder with cellular wall broken is dry in 45 DEG C of baking ovens Dry to constant mass, take 15g Ganoderma spore powder with cellular wall broken in apparatus,Soxhlet's, with petroleum ether as solvent, 60 DEG C of reflux, extract, 8h, Obtaining petroleum ether extraction liquid, gained extract, after decompression distillation, uses anhydrous Na2SO4It is dried 24h, collects oil sample.
Described supercritical CO2Extraction obtains concretely comprising the following steps of Ganoderma spore oil: Ganoderma spore powder with cellular wall broken is 45 DEG C of bakings Case is dried to constant mass, takes 100g Ganoderma spore powder with cellular wall broken and be placed in the extraction axe of 1L and extract, extracting pressure 14MPa, extraction temperature 34 DEG C, extraction time 5h, CO2Flow 25L/h, collects oil sample.
Described microwave loss mechanisms obtains concretely comprising the following steps of Ganoderma spore oil: Ganoderma spore powder with cellular wall broken is dry in 45 DEG C of baking ovens Dry to constant mass, take 20g Ganoderma spore powder with cellular wall broken, be placed in extraction pot by water-soaked, add oil by solid-liquid ratio 15:1 Ether, puts in microwave equipment and extracts, microwave power 825W, temperature 45 C, extraction time 20min, extracts and uses suction method after terminating Separate solvent mixture and residue, washing residue 2-3 time, merge gained filtrate, after decompression distillation, use anhydrous Na2SO4It is dried 24h, collects oil sample.
Described ultrasonic extraction obtains concretely comprising the following steps of Ganoderma spore oil: Ganoderma spore powder with cellular wall broken is in 45 DEG C of baking ovens It is dried to constant mass, takes 20g Ganoderma spore powder with cellular wall broken in triangular flask, add petroleum ether by solid-liquid ratio 15:1, rock triangle Bottle, makes Ganoderma spore powder completely attach to lixiviating solution, triangular flask is put in ultrasonic processor and extracts.Ultrasonic power 350W, temperature 40 DEG C, extraction time 30min, extract 3 times.Extraction terminate after with suction method separation solution, washing residue 2-3 time, Merge gained filtrate, after decompression distillation, use anhydrous Na2SO4It is dried 24h, collects oil sample.
Advantages of the present invention and application effect:
For the medicine of other treatment cardiovascular disease current, the present invention has a following beneficial effect: (1) Ganoderma spore oil is a kind of pure natural medical, and toxic and side effects is little, both can serve as medicine, can serve as prophylactic agent;(2) Present invention application cardiovascular disease model and non-invasive ultrasound technology organically combine, and make up the limitation of conventional model, make reality Test result closer to truth;(3) present invention demonstrates Ganoderma spore oil application effect in prevention and cure of cardiovascular disease first Really.
[accompanying drawing explanation]
Fig. 1 is the left ventricle ultrasonography of hypertension cardiovascular disease model mice in the embodiment of the present invention;
Fig. 2 is the left ventricular wall thickness (systole) of hypertension cardiovascular disease model mice in the embodiment of the present invention;
Fig. 3 is the left ventricular ejection fraction of hypertension cardiovascular disease model mice in the embodiment of the present invention;
Fig. 4 is the painstaking effort output of each experimental mice in the embodiment of the present invention;
Fig. 5 is the ejection fraction of each experimental mice in the embodiment of the present invention;
Fig. 6 is the shortening fraction of each experimental mice in the embodiment of the present invention;
Fig. 7 is the left ventricle diameter of each experimental mice in the embodiment of the present invention.
[detailed description of the invention]
In order to verify the application effect of the present invention, below in conjunction with embodiment, the present invention is described in further detail, but Embodiments of the present invention are not limited to this.In the case of not specified (NS), reagent, equipment and the method that the present invention uses is this Technical field conventional commercial reagent, equipment and conventional use of method.
Cardiovascular disease method for establishing model: open mice thoracic cavity and expose left coronary artery descending branch, 2mm below left auricle Place's 6-0 silk thread Ligation of artery, sews up routinely after ligation and cervical region subcutaneous injection 0.5ml normal saline is in case dehydration, postoperative Carry out routine care, with sham operated rats (sham operated rats only suture is not tied a knot) for contrast, utilize whether ultrasound examination model becomes Merit, finds after testing: myocardium of left ventricle is plump, and the chambers of the heart becomes big, and ejection fraction reduces and thickens along with ventricle wall and mitochondrion Textural anomaly (as Figure 1-3), illustrates that hypertension cardiovascular disease model is successfully established.
The preparation of Ganoderma spore oil: Ganoderma spore oil used in the present embodiment is to use Application No. Method described in 200610035574.8 patents of invention obtains, but the Ganoderma spore oil in the present invention is not limited thereto.
Experimental design and packet: experiment mice uses random numbers table method be randomly divided into 4 groups, except Normal group 3 Outside mice, remaining group is 6 mices, male and female half and half, and the process of each group mice is as follows:
Given the test agent administration group: be first administered with Ganoderma spore oil 1 week, dosage is 3g/ (kg BW), after modeling successfully, continues Continuous administration 2 weeks;
Positive controls: gavage positive drug propranolol, dosage: 10mg/kg, continuous every day, gavage 1 week, modeled successfully After, continue to be administered 2 weeks;
Normal group: gavage and the isodose solvent of Ganoderma spore oil 1 week, replaces modeling Post operation with sham-operation, continues Continuous gavage 2 weeks;
Model control group: gavage and the isodose solvent of Ganoderma spore oil 1 week, after modeling successfully, continuation gavage 3 weeks.
Feeding and management and detection method: use standard feed and tap water to feed, raise in constant temperature (22 ± 2) DEG C, constant humidity (55 ± 5) %, each 12h of artificial lighting light and shade quiet receptacle in, after 3 weeks, mice is through induced anesthesia, and chest loses hair or feathers, and regulation is super Sonic probe position is to obtain parasternal long axis B-Mode image, the most again under M-mode image, gathers systole and relaxing period is left Room chamber wall thickness and internal diameter data, calculate Left Ventricular Ejection Fraction, its cardiac function is analyzed, result as shown in figs. 4-7: with mould Type matched group ratio, gavage Ganoderma spore oil, cardiac function can be improved, ejection fraction reaches 66.02, close to blank group numerical value; Painstaking effort output also has preferably improvement, the especially vasodilation abilities of left ventricle to have substantially change.
Based on the above results, Ganoderma spore oil has prevention and auxiliary therapeutic action to hypertension cardiovascular disease, logical Cross improvement painstaking effort output, LV Diastolic ability, ejection fraction, thus play prevention or the effect for the treatment of, can be applicable to people The treatment of class cardiovascular related diseases.
The above, the only preferably specific embodiment of the present invention, but protection scope of the present invention is not limited thereto, Any those familiar with the art in the technical scope that the invention discloses, according to technical scheme and Conceive in addition equivalent or change, all should contain within the scope of the present invention.

Claims (5)

1. Ganoderma spore oil application in preparing prevention and cure of cardiovascular disease medicine.
Application the most according to claim 1, it is characterised in that described cardiovascular disease is hypertension cardiovascular disease.
Application the most according to claim 2, it is characterised in that the effective dose of described Ganoderma spore oil is 3g/ (kg BW)。
4. according to the application according to any one of claim 1-3, it is characterised in that described Ganoderma spore oil passes through soxhlet extraction Method, supercritical CO2A kind of acquisition in extraction, microwave loss mechanisms and ultrasonic extraction.
Application the most according to claim 4, it is characterised in that
Described soxhlet extraction method obtains the concretely comprising the following steps of Ganoderma spore oil: Ganoderma spore powder with cellular wall broken be dried in 45 DEG C of baking ovens to Constant mass, takes 15g Ganoderma spore powder with cellular wall broken in apparatus,Soxhlet's, with petroleum ether as solvent, and 60 DEG C of reflux, extract, 8h, obtain Petroleum ether extraction liquid, gained extract, after decompression distillation, uses anhydrous Na2SO4It is dried 24h, collects oil sample.
Described supercritical CO2Extraction obtains concretely comprising the following steps of Ganoderma spore oil: Ganoderma spore powder with cellular wall broken is dry in 45 DEG C of baking ovens Dry to constant mass, take 100g Ganoderma spore powder with cellular wall broken and be placed in the extraction axe of 1L and extract, extracting pressure 14MPa, extraction Temperature 34 DEG C, extraction time 5h, CO2Flow 25L/h, collects oil sample.
Described microwave loss mechanisms obtains the concretely comprising the following steps of Ganoderma spore oil: Ganoderma spore powder with cellular wall broken be dried in 45 DEG C of baking ovens to Constant mass, takes 20g Ganoderma spore powder with cellular wall broken, is placed in extraction pot by water-soaked, adds petroleum ether by solid-liquid ratio 15:1, puts Enter in microwave equipment and extract, microwave power 825W, temperature 45 C, extraction time 20min, extract and separate molten with suction method after terminating Agent composition and residue, washing residue 2-3 time, merge gained filtrate, after decompression distillation, use anhydrous Na2SO4It is dried 24h, receives Collection oil sample.
Described ultrasonic extraction obtains concretely comprising the following steps of Ganoderma spore oil: Ganoderma spore powder with cellular wall broken is dried in 45 DEG C of baking ovens To constant mass, take 20g Ganoderma spore powder with cellular wall broken in triangular flask, add petroleum ether by solid-liquid ratio 15:1, rock triangular flask, make Ganoderma spore powder completely attaches to lixiviating solution, triangular flask is put in ultrasonic processor and extracts.Ultrasonic power 350W, temperature Spend 40 DEG C, extraction time 30min, extract 3 times.Extraction terminate after with suction method separation solution, washing residue 2-3 time, merging institute Obtain filtrate, after decompression distillation, use anhydrous Na2SO4It is dried 24h, collects oil sample.
CN201610630693.1A 2016-08-03 2016-08-03 Ganoderma spore oil application in preparing prevention and cure of cardiovascular disease medicine Pending CN106138117A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021102571A (en) * 2019-12-25 2021-07-15 ロート製薬株式会社 Hypertensive heart disease treatment agent
CN113876818A (en) * 2021-10-15 2022-01-04 南京中科药业有限公司 Compound ganoderma lucidum spore oil extract for preventing stroke and preparation method and application thereof
CN114340651A (en) * 2019-05-10 2022-04-12 梅约医学教育与研究基金会 Methods and materials for treating cardiovascular disease
CN114752431A (en) * 2022-04-26 2022-07-15 山东芝人堂药业有限公司 Extraction and deep processing technology of high-purity triterpene ganoderma lucidum spore oil

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114340651A (en) * 2019-05-10 2022-04-12 梅约医学教育与研究基金会 Methods and materials for treating cardiovascular disease
EP3965796A4 (en) * 2019-05-10 2022-07-06 Mayo Foundation for Medical Education and Research Methods and materials for treating cardiovascular diseases
JP2021102571A (en) * 2019-12-25 2021-07-15 ロート製薬株式会社 Hypertensive heart disease treatment agent
JP7495075B2 (en) 2019-12-25 2024-06-04 ロート製薬株式会社 Hypertensive heart disease treatment
CN113876818A (en) * 2021-10-15 2022-01-04 南京中科药业有限公司 Compound ganoderma lucidum spore oil extract for preventing stroke and preparation method and application thereof
CN114752431A (en) * 2022-04-26 2022-07-15 山东芝人堂药业有限公司 Extraction and deep processing technology of high-purity triterpene ganoderma lucidum spore oil

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Application publication date: 20161123