CN109528933A - A kind of application of the compound formulation including tomorrow leaf in prevention or medicaments for treating sexual disorder - Google Patents
A kind of application of the compound formulation including tomorrow leaf in prevention or medicaments for treating sexual disorder Download PDFInfo
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- CN109528933A CN109528933A CN201811642617.8A CN201811642617A CN109528933A CN 109528933 A CN109528933 A CN 109528933A CN 201811642617 A CN201811642617 A CN 201811642617A CN 109528933 A CN109528933 A CN 109528933A
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- tomorrow leaf
- medicinal extract
- dendrobium candidum
- fructus lycii
- extract
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
- A61K36/815—Lycium (desert-thorn)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
- A61K36/8984—Dendrobium
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
-
- 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
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- 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
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- 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
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
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Abstract
The preparation method that a kind of compound preparation made of tomorrow leaf, dendrobium candidum and fructus lycii is specifically disclosed the invention belongs to pharmaceutical technology field and its application in the drug of prevention or the treatment of sexual dysfunction.By the way that compound preparation is made after mixing tomorrow leaf medicinal extract, dendrobium candidum medicinal extract and fructus lycii medicinal extract, experiments have shown that riding number, increasing sperm quantity in sex dysfunction when it can increase the sexual behaviour in castration male mice, meanwhile the content of testosterone, luteotropin, follicle-stimulating hormone and serotonin in serum in sex dysfunction individual can be improved.In addition, it is more complete, well arranged using the tissue result of testis in the histology and morphology structure of mouse testis after compound formulation of the invention, with the presence of more spermatid.The active principle of improvement sex dysfunction preparation of the invention is clear, curative effect is determining, has no toxic side effect, and extracting method is easy to implement, has a extensive future.
Description
Technical field
The present invention relates to pharmaceutical technology fields, are more particularly to one kind and are prepared by tomorrow leaf, dendrobium candidum and fructus lycii
Compound formulation and preparation method thereof and the application in preparation prevention or medicaments for treating sexual disorder.
Background technique
The male sexual disfunction of painful topic can influence the normal life between man and wife to a certain extent, when serious very
Stablize to family is jeopardized.It is estimated that at least several hundred million men of global range suffer from different degrees of sex dysfunction.In the upper of China
Nearly 2,000 40 years old or more city males were once investigated in sea, and discovery male sexual disfunction disease incidence is up to 73%.
The function of hypothalamic pituitary gonadal axis sex hormone in patient's body of sex dysfunction is typically all disorder, often
Show as that internal testosterone levels are low, the low of testosterone levels follotropin and can promote corpus luteum and generate in feedback inhibition body
Hormone increases, and also further suppresses the generation of testosterone.So the measurement of sex hormone level can be good at evaluating male's property function
Index (identical Analysis of sex hormones in erectile dysfunction cases [J] of Zhao Guangbi, Huang Xianguo, Ye Zhi of energy obstacle
Anhui medicine, 2006 (03): 201-202).
Clinically male sexual disfunction form of expression multiplicity, it is main to cash in penile erectile dysfunction, premature ejaculation, hyposexuality
Etc. symptoms., mainly there is a 1. biological factor in the reason of having report to point out, causing male sexual disfunction, such as over fatigue, chronic
Disease, endocrine disorder etc. account for the 76.29% of statistical number.2. psychological factor, previous property experience, the attitude and anxiety of mistake
Etc. psychological factors can also cause sex dysfunction.3. cultural factor etc..Clinically given accordingly according to the concrete reason of patient
Treatment, generally all can from psychology, massage, the methods of drug and diet be treated (Xie Zongwei male sexual disfunction it is common
Performance and remedy measures inquire into medicine forum, [J] base, 2016,20 (30): 4220-4221.).Clinically doctor trained in Western medicine is to male's property
The therapeutic effect of dysfunction is not significant, there is also adverse reaction when serious, brings further burden to the psychology of patient.
This also indicate that safety and can solve root problem drug or means it is limited so that numerous male patients fall into the serious illness and be unable to from
It pulls out.
Male sexual disfunction increases many spiritual worries to patient to a certain extent, and undesirable psychology is pierced
Swashing further influences sexual function, to form a kind of vicious circle.In addition, " Plain Questions faint opinion " cloud: " Yang Mingzhe, the five internal organs six
The sea of internal organs, main profit penis；If Qi and blood deficiency, Yang Dao loses its honor and supports, then penis is difficult to run business into strong one " illustrate male sex organ according to resistance in spleen
Stomach Qi blood supports.Therefore, " treatment through spleen impotence " is also not answer the ignored important rules for the treatment of.Furthermore also there is doctor to think " all
Impotence in male does not rise, and mostly by the Yang-function insufficiency of kidneyzang, vital essence void is cold, or with seven feelings overstrains, damages the gas of raw sun, so that penis relaxes, and
For impotence weak person ", it is indicated that male sexual disfunction is related with kidney deficiency, liver depression.Therefore tcm clinical practice also show using kidney tonifying tune liver method come
It treats male sexual disfunction (impotence).But currently, in the relevance theory that spleen deficiency, deficiency of the kidney, liver depression influence sexual function
It inquires into less, it is also imperfect, and modern medicine Related Experimental Study is less, and not deeply.
Summary of the invention
For the deficiencies in the prior art, the purpose of the present invention is to provide one kind to be applied to prevention or therapeutic function
The drug of energy obstacle.
Present inventor has been devoted to the prevention and treatment effect that research tomorrow leaf damages liver for many years, for a long time
Research and a large amount of experimental result confirm that tomorrow leaf has and adjust liver and liver protection effect, can improve energy generation by adjusting rouge protect liver
It thanks, alleviates organism fatigue, it is vigorous to make one recovery morning；There is classic medicine nationality record dendrobium candidum kidney tonifying product essence, invigorating the spleen to help fortune, increase strength
The effect of, a large amount of basic research discovery dendrobium candidum nephrotic syndrome caused by kidney deficiency model and chemotherapeutics has antagonism
Effect；And fructus lycii has the effect of nourishing the liver, nourshing kidney and strengthen immunity.
In conjunction with the theory of medicine of Chinese medicine " adjusting liver, invigorating the spleen, kidney tonifying " treatment impotence, applicant answers a kind of tomorrow leaf that includes
Close whether preparation there is the curative effect for improving sex dysfunction to have done a large amount of scientific experiment research, by establishing sex dysfunction
(castration mouse model) model studies a kind of compound formulation for including tomorrow leaf and therapeutic effect to corresponding illness is administered.Research
The result shows that the property row that can be remarkably reinforced in sex dysfunction after a kind of compound formulation administration for including tomorrow leaf of compound preparation
To learn ability, the sex hormone level in sex dysfunction is improved, and restore testis tissue form in sex dysfunction.
To achieve the goals above, present invention employs following technical measures:
A method of extracting a kind of drug for including tomorrow leaf from tomorrow leaf, dendrobium candidum and fructus lycii, including as follows
Step:
(1) preparation of tomorrow leaf medicinal extract
Dry tomorrow leaf (being rounded strain tomorrow leaf) is taken, is placed in extractor after crushing, alcohol reflux is added and extracts at least 2
Secondary, combined extract is concentrated under reduced pressure after filtering, freeze-drying obtains tomorrow leaf medicinal extract；
(2) preparation of dendrobium candidum medicinal extract
Dry dendrobium candidum (dry dendrobium candidum stem) is taken, is placed in extractor, adds water heating extracting at least 2 times after crushing, is closed
And extracting solution, it is concentrated under reduced pressure after filtering, freeze-drying obtains dendrobium candidum medicinal extract；
(3) preparation of fructus lycii medicinal extract
Dry fructus lycii is taken, is placed in extractor after crushing, alcohol reflux is added and extracts at least 2 times, combined extract, mistake
It is concentrated under reduced pressure after filter, freeze-drying obtains fructus lycii medicinal extract；
(4) dendrobium candidum medicinal extract that tomorrow leaf medicinal extract that step (1) obtains, step (2) obtain, step (3) are obtained
Fructus lycii medicinal extract, according to (5-10): 1: the weight ratio of (5-10) is uniformly mixed, and obtains a kind of drug for including tomorrow leaf.
Further, a kind of side extracting a kind of compound formulation for including tomorrow leaf from tomorrow leaf, dendrobium candidum and fructus lycii
Method includes the following steps:
(1) preparation of tomorrow leaf medicinal extract
Dry tomorrow leaf (being rounded strain tomorrow leaf) is taken, is placed in extractor after crushing, 50-80v/v% is added thereto
1-2 hours each after ethanol water refluxing extraction 2-3 times at 60-80 DEG C, combined extract is concentrated under reduced pressure after filtering, is cold
Jelly is dried to obtain tomorrow leaf medicinal extract；
(2) preparation of dendrobium candidum medicinal extract
Dry dendrobium candidum (dry dendrobium candidum stem) is taken, is placed in extractor after crushing, is added after water at 60-80 DEG C thereto
Lower to extract 2-3 times, 1-1.5 hours each, combined extract is concentrated under reduced pressure after filtering, freeze-drying obtains dendrobium candidum medicinal extract；
(3) preparation of fructus lycii medicinal extract
Dry fructus lycii is taken, is placed in extractor after crushing, is added after 70-90v/v% ethanol water in 60- thereto
Refluxing extraction 2-3 times at 80 DEG C, 1.5-2 hours each, combined extract is concentrated under reduced pressure after filtering, freeze-drying obtains fructus lycii
Medicinal extract；
(4) dendrobium candidum medicinal extract that tomorrow leaf medicinal extract that step (1) obtains, step (2) obtain, step (3) are obtained
Fructus lycii medicinal extract, according to (5-10): 1: the weight ratio of (5-10) after mixing, crushes, obtains mixing extract powder；
(5) mixing being made of starch and dextrin of 1-2 times of its weight is added into the mixing extract powder that step (4) obtains
Object, starch and dextrin weight ratio are (3-6) in mixture: 1, softwood is made in the ethanol water for adding 95v/v%, then makes
Grain, obtains a kind of compound formulation for including tomorrow leaf.
Further, the amount ratio of tomorrow leaf and the ethanol water being added every time dry in the step (1) is
1kg:(5-10) L.
Further, the amount ratio of dry dendrobium candidum and the water being added every time is 1kg:(5-10 in the step (2)) L.
Further, fructus lycii dry in the step (3) and the amount ratio for the ethanol water being added every time are 1kg:
(5-10)L。
Further, crushing described in step (1)-step (4) refers both to be crushed to 60-100 mesh powder.
A kind of drug for including tomorrow leaf for being obtained the present invention also provides above-mentioned preparation method, a kind of tomorrow leaf that includes
Application of the compound formulation in prevention or medicaments for treating sexual disorder, experiment proves that, significant effect.
Compared with prior art, the present invention has the following advantages and effects:
1, a kind of product for including raw material needed for the preparation of tomorrow leaf and taking from " food and medicine consangunity " are originated from naturally, are easier to
For patient's receiving；Entire extracting method, preparation process are simple, easy to implement.
2, a kind of drug for including tomorrow leaf or compound formulation prepared by the present invention can effectively treat sex dysfunction, table
Incubation period before the sexual behaviour in sex dysfunction can be shortened now, riding time when increasing the sexual behaviour in sex dysfunction
Number increases sperm quantity in sex dysfunction.Meanwhile a kind of drug for including tomorrow leaf or compound formulation can maintain sexual function
In obstacle in serum testosterone, luteotropin, follicle-stimulating hormone and 5-HT content, and the normal tissue shape of testis can be maintained
State.Compared with existing mainstream therapies, a kind of drug including tomorrow leaf or compound formulation the treatment of sexual dysfunction have effect
The advantages such as good, cheap.
3, the length of a kind of drug for including tomorrow leaf or compound formulation collection tune liver, invigorating the spleen, kidney tonifying, is scientifically combined one
It rises, multiple target point collective effect is more more effective than being applied alone, and is adapted to the sex dysfunction group of the different constitutions such as spleen deficiency, deficiency of the kidney, liver depression
Body.
Detailed description of the invention
Fig. 1 is a kind of compound formulation for including tomorrow leaf of the preparation of embodiment 1 to sex dysfunction mouse sexual behaviour ability
Influence diagram.
Fig. 2 is a kind of sex hormone water of compound formulation for including tomorrow leaf to sex dysfunction mouse of the preparation of embodiment 1
Flat influence diagram.
Fig. 3 is that a kind of compound formulation for including tomorrow leaf prepared by embodiment 1 restores testis tissue shape in sex dysfunction
State figure.
Specific embodiment
Applicant will in conjunction with specific embodiments be described in further detail technical solution of the present invention below.Ying Li
Solution, the following contents should not be construed as in any way the limitation to protection scope of the present invention.
It is real that applicant has carried out serial, a large amount of science to a kind of compound formulation the treatment of sexual dysfunction for including tomorrow leaf
Verifying confirms that the sexology ability in sex dysfunction can be enhanced in the compound, improves the sex hormone in sex dysfunction
Level, and restore testis tissue form in sex dysfunction.
The assay of Dendrobium officinale polysaccharide is referring to following pertinent literature: the People's Republic of China (PRC), Chinese Pharmacopoeia Commission
Mono- Beijing [M] pharmacopeia: China Medical Science Press, 2015:283；
The detection method of polysaccharides is referring to following pertinent literature: Chinese Pharmacopoeia Commission Pharmacopoeia of People's Republic of China
One Beijing [M]: China Medical Science Press, 2015:249.
A kind of a kind of side that compound formulation for including tomorrow leaf is extracted from tomorrow leaf, dendrobium candidum and fructus lycii of embodiment 1
Method includes the following steps:
(1) preparation of tomorrow leaf medicinal extract
The whole strain tomorrow leaf for taking 5kg dry is ground into 80 mesh powder, is placed in extractor, is added 25L's thereto every time
50% (v/v) ethanol water, refluxing extraction 2 times at 60 DEG C 2 hours every time, merge 2 extracting solutions, are concentrated under reduced pressure, are cold
Jelly is dried to obtain tomorrow leaf extract powder 800.0g, and the content for measuring this extract powder Content of Chlorogenic Acid is 3.6wt%, spare.
(2) preparation of dendrobium candidum medicinal extract
It takes the dry dendrobium candidum stem of 2.5kg to be ground into 80 mesh powder, is placed in extractor, add 12.5L water thereto every time,
Constant temperature extracts 2 times at 60 DEG C, 1.5 hours every time, merges 2 extracting solutions, is concentrated under reduced pressure, freeze-drying obtains dendrobium candidum
Extract powder 245.0g, the content for measuring Dendrobium officinale polysaccharide in this extract powder is 35.67wt%, spare.
(3) preparation of fructus lycii medicinal extract
It takes dry fructus lycii 5kg to be ground into 80 mesh powder, is placed in extractor, be added the 70% of 25L thereto every time
(v/v) ethanol water, refluxing extraction 2 times at 60 DEG C 2 hours every time, merge 2 extracting solutions, are concentrated under reduced pressure, freezing is done
Dry to obtain fructus lycii extract powder 495.9g, the content for measuring wherein polysaccharides is 19.06wt%, spare.
(4) dendrobium candidum extract powder 100g that the tomorrow leaf extract powder 500g that takes step (1) to obtain, step (2) obtain, step
Suddenly the fructus lycii extract powder 500g that (3) obtain is mixed, and is ground into 80 mesh powder after mixing, is obtained mixing extract powder；
(5) mixing that 2 times of its weight is added into the mixing extract powder that step (4) obtains, being made of starch and dextrin
Object (starch and dextrin weight ratio 4: 1 in mixture), after mixing, under stiring, then with spray pattern, total amount is added thereto is
95% (v/v) ethanol water of 100mL is uniformly mixed and softwood is made, then uses compressed particle mechanism grain, and sabot enters 60 DEG C
It is 24 hours dry in baking oven, a kind of granule for including tomorrow leaf is obtained, i.e., a kind of compound formulation for including tomorrow leaf.
A kind of a kind of side that compound formulation for including tomorrow leaf is extracted from tomorrow leaf, dendrobium candidum and fructus lycii of embodiment 2
Method includes the following steps:
(1) preparation of tomorrow leaf medicinal extract
The whole strain tomorrow leaf for taking 5kg dry is ground into 80 mesh powder, is placed in extractor, is added 50L's thereto every time
80% (v/v) ethanol water, refluxing extraction 3 times at 80 DEG C 1 hour every time, merge 3 extracting solutions, are concentrated under reduced pressure, are cold
Jelly is dried to obtain tomorrow leaf extract powder 1000.0g, and the content for measuring this extract powder Content of Chlorogenic Acid is 3.9wt%, spare.
(2) preparation of dendrobium candidum medicinal extract
It takes the dry dendrobium candidum stem of 2.5kg to be ground into 80 mesh powder, is placed in extractor, every time thereto plus 25 L water, 80
Constant temperature extracts 3 times at DEG C, 1 hour every time, merges 3 extracting solutions, is concentrated under reduced pressure, freeze-drying obtains dendrobium candidum extract powder
332.6g, the content for measuring Dendrobium officinale polysaccharide in this extract powder is 41.46wt%, spare.
(3) preparation of fructus lycii medicinal extract
It takes dry fructus lycii 5kg to be ground into 80 mesh powder, is placed in extractor, be added the 90% of 50L thereto every time
(v/v) ethanol water, refluxing extraction 3 times at 80 DEG C 1.5 hours every time, merge 3 extracting solutions, are concentrated under reduced pressure, freezing
It is dried to obtain fructus lycii extract powder 572.3g, the content for measuring wherein polysaccharides is 21.37wt%, spare.
(4) dendrobium candidum extract powder 50g that the tomorrow leaf extract powder 500g that takes step (1) to obtain, step (2) obtain, step
Suddenly the fructus lycii extract powder 500g that (3) obtain is mixed, and is ground into 80 mesh powder after mixing, is obtained mixing extract powder；
(5) mixing that 2 times of its weight is added into the mixing extract powder that step (4) obtains, being made of starch and dextrin
Object (starch and dextrin weight ratio 4: 1 in mixture), after mixing, under stiring, then with spray pattern, total amount is added thereto is
95% (v/v) ethanol water of 100mL is uniformly mixed and softwood is made, then uses compressed particle mechanism grain, and sabot enters 60 DEG C
24 hours are dried in baking oven to get a kind of granule for including tomorrow leaf, i.e., a kind of compound formulation for including tomorrow leaf.
A kind of influence of the compound formulation for including tomorrow leaf of embodiment 3 to castration male mice sexology ability
Animal subject is youth (8 week old) mouse of SPF grades of Kunming males, old age (60 week old) mouse each 20 and elder brother
Bright female is young (8 week old) mouse 40 (being provided by Disease Prevention Control Center, Hubei Prov).Free water diet raises compartment
Temperature is maintained at 25 ± 1 DEG C, and the light and shade period is 12 hours.
1, the modeling and administration of castration male mice
Green, Old Male mouse is respectively divided into 5 groups: blank control group, a kind of includes the compound of tomorrow leaf at model group
Preparation low dose group, a kind of compound formulation high dose group including tomorrow leaf, testosterone propionate group.Except the daily muscle of blank control group
Outside injecting normal saline, remaining each group mouse daily intramuscular injection hydroprednisone acetate 25mg/kg, 1 times/day, continuous 7
It.A kind of compound formulation low dose group including tomorrow leaf and a kind of compound formulation high dose group mouse for including tomorrow leaf are in every
Immediately give corresponding dosage a kind of compound formulation stomach-filling (respectively 1650mg/kg/ for including tomorrow leaf after day prednisone injection
Day and 5000mg/kg/day, directly with a kind of compound formulation weight metering for including tomorrow leaf), one kind used includes tomorrow leaf
Compound formulation be embodiment 1 prepare a kind of granule physiological saline for including tomorrow leaf disperse to obtain, 1 times/day, continuously
7 days.Testosterone propionate group mouse gives testosterone propionate subcutaneous injection (1 mg/kg/ after daily hydroprednisone acetate is injected
Day), 1 times/day, continuous 7 days.
2, mating test
Entire observation procedural arrangements carry out at night, and light is dimmed to enough observations, every male mice and one
The independent cage of female mice, observation total time are 30min, record the capture incubation period of every male mouse (with female mice with cage to the
The time required to once riding) and rider number.Gametocide mouse is cutd open after experiment, and its right testicle is shredded and calculates sperm survival
Rate: the test tube for filling 6ml physiological saline being placed in constant water bath box and is preheated to 37 DEG C, is then shredded left side epididymis and is put into examination
It is shaken up in pipe, in 37 DEG C of 10~15min of heat preservation, keeps sperm sufficiently free.It is instilled after taking drop dilution certain multiple in test tube
On blood cell counting plate, number of motile sperm (N) in 5 medium squares is counted under 200 power microscopes, every milliliter of number of motile sperm is N
× 5 × extension rate × 104。
3, experimental result
After 7 days, the index of mouse sexology is measured, as a result as shown in Figure 1.
Compared with normal group, after intramuscular injection hydroprednisone acetate, in young castration male mice model, mouse is dived
The volt phase significantly extends (P < 0.05), rides number and motile sperm number significantly reduces (P < 0.01, P < 0.05).Low dosage
A kind of compound formulation for including tomorrow leaf of Chinese medicine compound prescription can be such that 11.4 ± 3.3min of the incubation period before young mouse sexual behaviour shortens
It is 10.0 ± 1.9min, motile sperm number by (4.8 ± 1.8) × 106A/ml increases to (8.7 ± 3.0) × 106A/ml (P <
0.05).A kind of compound formulation effect for including tomorrow leaf of the Chinese medicine compound prescription of high dose is more obvious, can with conspicuousness shorten blueness
Incubation period (6.9 ± 1.4min, P < 0.05 are shorten to by 11.4 ± 3.3min) before year mouse sexual behaviour, increase ride number,
Motile sperm quantity is obviously increased, motile sperm quantity is by (4.8 ± 1.8) × 106A/ml increases to (5.4 ± 1.3) × 106
A/ml, P < 0.05.
Compared with normal group, after intramuscular injection hydroprednisone acetate, in aged castration male mice model, mouse is dived
The volt phase significantly extends (P < 0.05), rides number and significantly reduces (P < 0.05) and the reduction of motile sperm number.The Chinese medicine of low dosage
A kind of compound formulation function and effect variation tendency for including tomorrow leaf of compound is little, it is contemplated that aged mouse is physiologically due to this
The reason of body sexual behaviour ability reduces.A kind of compound formulation effect for including tomorrow leaf of the Chinese medicine compound prescription of high dose is obvious,
Aged Mice can be increased rides number (being increased by 2.60 ± 1.5 times by 1.80 ± 0.84 times), and motile sperm quantity is by 7.13
±0.52×106It is 8.64 ± 2.04 × 10 that a/ml, which increases,6A/ml.
A kind of influence of the compound formulation for including tomorrow leaf of embodiment 4 to castration male mice hormone serum level
1, the detection of castration male mice serum Biochemical Indexes
By the experiment hero mouse in embodiment 3 in the 7th administration, post-coitum, anesthesia is put to death, is detected using enzyme-linked method kit
The indexs such as testosterone, luteotropin, follicle-stimulating hormone and serotonin (5-HT) in serum.
2, experimental result
As a result as shown in Fig. 2, in every group of data, respectively blank group, model group, a kind of tomorrow leaf that includes from left to right
Compound formulation low dose group, a kind of compound formulation high dose group and testosterone propionate group for including tomorrow leaf.Younger group result is as follows:
Compared with normal group, after intramuscular injection hydroprednisone acetate, the horizontal aspect of serum biochemistry, Young adult male model group mice serum testis
Ketone, luteotropin level decline (P < 0.01, P < 0.05 compared with normal group), 5-HT content are reduced.Low, high dose one kind
The compound formulation for including tomorrow leaf can make the testosterone concentration in serum be increased to 5.0 ± 1.1mol/ respectively by 2.4 ± 0.5mol/L
L and 8.8 ± 1.7mol/L (P < 0.01), Luteinoid content be increased to 29.2 by 13.7 ± 0.8mIU/mL respectively ±
The content of 6.3mIU/mL and 43.4 ± 4.3 (P < 0.01), 5-HT is increased to 51.8 by 45.9 ± 2.7ng/mL respectively ±
0.7ng/mL and 55.6 ± 1.6ng/mL (P < 0.05).
Old age group result is as follows: in aged male mice, compared with normal group, and after intramuscular injection hydroprednisone acetate,
The horizontal aspect of serum biochemistry, aged male model group mice serum testosterone, luteotropin, 5-HT content be decreased obviously (with it is normal
Group compares P < 0.01, P < 0.05, P < 0.05).A kind of low, high dose compound formulation for including tomorrow leaf can make the testis in serum
Ketone content be increased to respectively by 0.8 ± 1.5mol/L 2.4 ± 0.6 mol/L and 2.4 ± 0.5mol/L (P < 0.05, P < 0.05),
Luteinoid content be increased to respectively by 12.8 ± 0.8mIU/mL 16.6 ± 1.4mIU/mL and 22.1 ± 1.7 (P < 0.05, P <
0.05), the content of 5-HT be increased to respectively by 39.8 ± 3.5ng/mL 45.7 ± 1.7ng/mL and 53.8 ± 0.8ng/mL (P <
0.05)。
The follicle-stimulating hormone content difference of each experimental group is smaller.
A kind of compound formulation for including tomorrow leaf of embodiment 5 restores the testis tissue aspect graph of castration male mice
1, the observation of castration male mice testis tissue form
By the experiment hero mouse in embodiment 3 in the 7th administration, post-coitum, anesthesia is put to death, and takes experiment mice left testes solid
Determine investing tissue's slice, and hematoxylin-eosin HE dyeing is carried out to slice, observes the testis tissue form of male mice.
2, experimental result
Experimental result is as shown in figure 3, each phase androgone marshalling in normal group of mouse convoluted seminiferous tubule of Younger group, tight
Close, orderly, well arranged, spermatogonium is small and justifies, and is close to the basilar memebrane of Qu Jingguan, is inwardly followed successively by first spermatocyte, essence
Daughter cell and sperm, while sertoli cell form is normal.After intramuscular injection hydroprednisone acetate, male mice male model group mouse
Seminiferous tubule seminaferous epithelium is obviously thinning, and androgone falls off, cell level disorder, and spermatogonium, sperm mother cell are reduced, sperm
Cell and oligozoospermia are more obvious, interstitial glands Mild edema.A kind of compound formulation low dosage including tomorrow leaf is raw
Spermatid quantity is slightly reduced, and partial region sees that a small amount of androgone falls off, but is still higher than spermatid quantity in model group.In one kind
Compound formulation high dose mouse testis seminiferous tubule containing tomorrow leaf includes a large amount of sperms, and androgone arranges slightly loose, structure
Clear, well arranged, cell level is reduced, and spermatogonium quantity is normal, and form is round and regular.
The old age experimental result of group is as follows: after intramuscular injection hydroprednisone acetate, male model group mouse male model group is small
Mouse seminiferous tubule seminaferous epithelium is obviously thinning, and androgone falls off, cell level disorder, and spermatogonium, sperm mother cell are reduced, essence
Daughter cell and oligozoospermia are more obvious；In a kind of the low of the compound formulation including tomorrow leaf, high dose group mouse seminiferous tubule
Containing a large amount of sperms, androgone arrangement is slightly loose, and structure understands, well arranged.
A kind of compound formulation for including tomorrow leaf that the present invention obtains can significantly improve young, aged mouse sexuality energy
Power raises libido, and enhancing is erected, androgen levels, monoamine neurotransmitter 5-HT content in the mechanism of action and raising body
And sperm level is related.
A kind of compound formulation including tomorrow leaf prepared by 6 embodiment 2 of embodiment is to castration male mice sexology
The influence of ability
Animal subject is youth (8 week old) mouse of SPF grades of Kunming males, old age (60 week old) mouse each 20 and elder brother
Bright female is young (8 week old) mouse 40 (being provided by Disease Prevention Control Center, Hubei Prov).Free water diet raises compartment
Temperature is maintained at 25 ± 1 DEG C, and the light and shade period is 12 hours.
1, the modeling and administration of castration male mice
Green, Old Male mouse is respectively divided into 5 groups: blank control group, a kind of includes the compound of tomorrow leaf at model group
Preparation low dose group, a kind of compound formulation high dose group including tomorrow leaf, testosterone propionate group.Except the daily muscle of blank control group
Outside injecting normal saline, remaining each group mouse daily intramuscular injection hydroprednisone acetate 25mg/kg, 1 times/day, continuous 7
It.A kind of compound formulation low dose group including tomorrow leaf and a kind of compound formulation high dose group mouse for including tomorrow leaf are in every
Immediately give corresponding dosage a kind of compound formulation stomach-filling (respectively 1650mg/kg/ for including tomorrow leaf after day prednisone injection
Day and 5000mg/kg/day, directly with a kind of compound formulation weight metering for including tomorrow leaf), one kind used includes tomorrow leaf
Compound formulation be embodiment 2 prepare a kind of granule physiological saline for including tomorrow leaf disperse to obtain, 1 times/day, continuously
7 days.Testosterone propionate group mouse gives testosterone propionate subcutaneous injection (1 mg/kg/ after daily hydroprednisone acetate is injected
Day), 1 times/day, continuous 7 days.
2, mating test
Entire observation procedural arrangements carry out at night, and light is dimmed to enough observations, every male mice and one
The independent cage of female mice, observation total time are 30min, record the capture incubation period of every male mouse (with female mice with cage to the
The time required to once riding) and rider number.Gametocide mouse is cutd open after experiment, and its right testicle is shredded and calculates sperm survival
Rate: the test tube for filling 6ml physiological saline being placed in constant water bath box and is preheated to 37 DEG C, is then shredded left side epididymis and is put into examination
It is shaken up in pipe, in 37 DEG C of 10~15min of heat preservation, keeps sperm sufficiently free.It is instilled after taking drop dilution certain multiple in test tube
On blood cell counting plate, number of motile sperm (N) in 5 medium squares is counted under 200 power microscopes, every milliliter of number of motile sperm is N
× 5 × extension rate × 104。
3, experimental result
After 7 days, the index of mouse sexology is measured.
Compared with normal group, after intramuscular injection hydroprednisone acetate, in young castration male mice model, mouse is dived
The volt phase significantly extends (P < 0.05), rides number and motile sperm number significantly reduces (P < 0.01, P < 0.05).Low dosage
A kind of compound formulation for including tomorrow leaf of Chinese medicine compound prescription can be such that 12.0 ± 3.5min of the incubation period before young mouse sexual behaviour shortens
It is 9.9 ± 1.8min, motile sperm number by (4.8 ± 1.7) × 106A/ml increases to (9.3 ± 1.7) × 106A/ml (P <
0.05).A kind of compound formulation effect for including tomorrow leaf of the Chinese medicine compound prescription of high dose is more obvious, can with conspicuousness shorten blueness
Incubation period (6.3 ± 1.1min, P < 0.05 are shorten to by 12.0 ± 3.4min) before year mouse sexual behaviour, increase ride number,
Motile sperm quantity is obviously increased, motile sperm quantity is by (4.8 ± 1.7) × 106A/ml increases to (8.2 ± 1.2) × 106
A/ml, P < 0.05.
Compared with normal group, after intramuscular injection hydroprednisone acetate, in aged castration male mice model, mouse is dived
The volt phase significantly extends (P < 0.05), rides number and significantly reduces (P < 0.05) and the reduction of motile sperm number.The Chinese medicine of low dosage
A kind of compound formulation for including tomorrow leaf of compound can make 8.7 ± 1.6min of incubation period before Aged Mice sexual behaviour shorten to 8.4
± 1.6min, motile sperm number are by (6.8 ± 1.1) × 106A/ml increases to (7.8 ± 1.3) × 106A/ml (P <
0.05).A kind of compound formulation effect for including tomorrow leaf of the Chinese medicine compound prescription of high dose is more obvious, can with conspicuousness shorten old
Incubation period (7.7 ± 1.7min, P < 0.05 are shorten to by 8.7 ± 1.6min) before year mouse sexual behaviour, increase ride number,
Motile sperm quantity is obviously increased, motile sperm quantity is by (6.2 ± 1.1) × 106A/ml increases to (8.8 ± 1.7) × 106
A/ml, P < 0.05.
A kind of influence of the compound formulation for including tomorrow leaf of embodiment 7 to castration male mice hormone serum level
1, the detection of castration male mice serum Biochemical Indexes
By the experiment hero mouse in embodiment 6 in the 7th administration, post-coitum, anesthesia is put to death, is detected using enzyme-linked method kit
The indexs such as testosterone, luteotropin, follicle-stimulating hormone and serotonin (5-HT) in serum.
2, experimental result
Younger group mice serum biochemistry detection result is as follows: young after intramuscular injection hydroprednisone acetate compared with normal group
Male model group mice serum testosterone, luteotropin level decline (P < 0.01, P < 0.05 compared with normal group), 5-HT content
It reduces.A kind of low, high dose compound formulation for including tomorrow leaf can make the testosterone concentration in serum by 2.6 ± 0.3mol/L points
It is not increased to 5.6 ± 1.3mol/L and 9.2 ± 1.4mol/L (P < 0.01), Luteinoid content by 14.1 ± 0.6mIU/mL points
The content for not being increased to 31.4 ± 5.2mIU/mL and 46.7 ± 3.3 (P < 0.01), 5-HT is risen respectively by 43.6 ± 2.4ng/mL
Up to 53.5 ± 0.6ng/mL and 58.3 ± 1.8ng/mL (P < 0.05).
Old age group result is as follows: in aged male mice, compared with normal group, and after intramuscular injection hydroprednisone acetate,
The horizontal aspect of serum biochemistry, aged male model group mice serum testosterone, luteotropin, 5-HT content be decreased obviously (with just
Normal group compares P < 0.01, P < 0.05, P < 0.05).A kind of low, high dose compound formulation for including tomorrow leaf can make in serum
Testosterone concentration be increased to respectively by 0.7 ± 0.2mol/L 2.8 ± 0.4mol/L and 3.2 ± 0.8mol/L (P < 0.05, P <
0.05), Luteinoid content be increased to respectively by 11.2 ± 0.6mIU/mL 17.6 ± 1.5mIU/mL and 23.3 ± 1.8 (P <
0.05, P < 0.05), the content of 5-HT be increased to respectively by 37.6 ± 2.7ng/mL 47.2 ± 1.3ng/mL and 55.1 ±
0.4ng/mL(P<0.05)。
Each experimental group follicle-stimulating hormone content difference is obvious.
Claims (7)
1. a kind of a kind of method that drug for including tomorrow leaf is extracted from tomorrow leaf, dendrobium candidum and fructus lycii, including walk as follows
It is rapid:
(1) preparation of tomorrow leaf medicinal extract
Dry tomorrow leaf is taken, is placed in extractor after crushing, alcohol reflux is added and extracts at least 2 times, combined extract, filtering
It is concentrated under reduced pressure afterwards, freeze-drying obtains tomorrow leaf medicinal extract；
(2) preparation of dendrobium candidum medicinal extract
Dry dendrobium candidum is taken, is placed in extractor, adds water heating extracting at least 2 times, combined extract depressurizes after filtering after crushing
Concentration, freeze-drying obtain dendrobium candidum medicinal extract；
(3) preparation of fructus lycii medicinal extract
Dry fructus lycii is taken, is placed in extractor after crushing, alcohol reflux is added and extracts at least 2 times, combined extract, after filtering
It is concentrated under reduced pressure, freeze-drying obtains fructus lycii medicinal extract；
(4) Chinese holly for obtaining dendrobium candidum medicinal extract that tomorrow leaf medicinal extract that step (1) obtains, step (2) obtain, step (3)
Qi medicinal extract is uniformly mixed according to 5-10: 1: 5-10 weight ratio, obtains a kind of drug for including tomorrow leaf.
2. a kind of a kind of method that compound formulation for including tomorrow leaf is extracted from tomorrow leaf, dendrobium candidum and fructus lycii, including such as
Lower step:
(1) preparation of tomorrow leaf medicinal extract
Dry tomorrow leaf is taken, is placed in extractor after crushing, is added after 50-80v/v% ethanol water in 60-80 thereto
Refluxing extraction 2-3 times at DEG C, 1-2 hours each, combined extract is concentrated under reduced pressure after filtering, freeze-drying obtains tomorrow leaf leaching
Cream；
(2) preparation of dendrobium candidum medicinal extract
Dry dendrobium candidum is taken, is placed in extractor after crushing, is extracted 2-3 times at 60-80 DEG C after water is added thereto, each 1-
1.5 hours, combined extract was concentrated under reduced pressure after filtering, freeze-drying obtains dendrobium candidum medicinal extract；
(3) preparation of fructus lycii medicinal extract
Dry fructus lycii is taken, is placed in extractor after crushing, is added after 70-90v/v% ethanol water at 60-80 DEG C thereto
Lower refluxing extraction 2-3 times, 1.5-2 hours each, combined extract is concentrated under reduced pressure after filtering, freeze-drying obtains fructus lycii medicinal extract；
(4) Chinese holly for obtaining dendrobium candidum medicinal extract that tomorrow leaf medicinal extract that step (1) obtains, step (2) obtain, step (3)
Qi medicinal extract, according to 5-10: 1: 5-10 weight ratio after mixing, crush, obtain mixing extract powder；
(5) mixture being made of starch and dextrin of 1-2 times of its weight is added into the mixing extract powder that step (4) obtains,
Starch and dextrin weight ratio are 3-6: 1 in mixture, and softwood is made in the ethanol water for adding 95 v/v%, and granulation obtains
A kind of compound formulation including tomorrow leaf.
3. according to the method described in claim 2, it is characterized in that, tomorrow leaf and addition every time dry in the step (1)
Ethanol water amount ratio be 1kg:5-10 L.
4. according to the method described in claim 3, it is characterized in that, in the step (2) dry dendrobium candidum be added every time
The amount ratio of water is 1kg:5-10 L.
5. according to the method described in claim 4, it is characterized in that, fructus lycii dry in the step (3) be added every time
The amount ratio of ethanol water is 1kg:5-10L.
6. according to the method described in claim 5, it is characterized in that, crushing described in step (1)-step (4) refers both to be crushed to
60-100 mesh powder.
7. any one of a kind of drug for including tomorrow leaf or claim 2-6 that a kind of method described in claim 1 obtains
A kind of application of the compound formulation for including tomorrow leaf that the method obtains in prevention or medicaments for treating sexual disorder.
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| CN112353872A (en) * | 2020-11-30 | 2021-02-12 | 中南民族大学 | Preparation method of compound preparation and application of compound preparation in preparation of medicine for preventing or treating sleep disorder |
| CN112646669A (en) * | 2021-01-25 | 2021-04-13 | 张晓峰 | Washing and protecting integrated laundry detergent containing biological protease |
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