CN110496148A - A kind of eucommia ulmoides extracts composition that treating the hypertension of pregnancy and its application - Google Patents
A kind of eucommia ulmoides extracts composition that treating the hypertension of pregnancy and its application Download PDFInfo
- Publication number
- CN110496148A CN110496148A CN201910896111.8A CN201910896111A CN110496148A CN 110496148 A CN110496148 A CN 110496148A CN 201910896111 A CN201910896111 A CN 201910896111A CN 110496148 A CN110496148 A CN 110496148A
- Authority
- CN
- China
- Prior art keywords
- pregnancy
- eucommia ulmoides
- parts
- ulmoides extracts
- hypertension
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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)
- A61K36/46—Eucommiaceae (Eucommia family), e.g. hardy rubber tree
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/35—Extraction with lipophilic solvents, e.g. Hexane or petrol ether
-
- 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
- A61K2236/55—Liquid-liquid separation; Phase separation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Botany (AREA)
- Emergency Medicine (AREA)
- Mycology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to Chinese medical extract fields, and in particular to a kind of eucommia ulmoides extracts composition for treating the hypertension of pregnancy and its application.The composition includes: 30-50 parts of 20-60 parts of mixed extract, the general flavone of 20-40 parts of ursolic acid, 10-25 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside.By enzymatic hydrolysis, step by step arithmetic, dissolution and etc. be made, preparation method is simple and efficient, and manufactured eucommia ulmoides extracts composition has preferable effect in terms of the treatment of the treatment hypertension of pregnancy, while reducing its side effect.
Description
Technical field
The invention belongs to Chinese medical extract fields, and in particular to a kind of eucommia ulmoides extracts composition for treating the hypertension of pregnancy
And its application.
Background technique
Gestation hypertension refers to that women gestation the symptoms such as hypertension, oedema, albuminuria occurs after 20 weeks, in transient,
It disappears after childbirth.One of the main reason for belonging to the peculiar disease of gestation, being current pregnant and lying-in women, peri-natal infant illness and death.In gestation
For later period systolic pressure more than 140 millimetress of mercury (18.7 kPas), diastolic pressure is more than 90 millimetress of mercury (12.0 kPas), it is necessary to examine
Consider hypertension.The reason of hypertension of pregnancy, there are many theories, it is considered that and it is that certain substance from placenta enters maternal blood,
Cause the immune factor of pregnant woman's body to change, lead to the whole body arteriolar spasm of pregnant woman and hypertension occurs, also studies have found that
It is related with inherent cause.Main clinical manifestation are as follows:
Hypertension: blood pressure reaches 140/90 millimetres of mercury twice, can make diagnosis.Albuminuria: midstream urine should be taken to carry out
It checks, it is abnormal that all twenty-four-hour urine protein quantifications, which are greater than 0.5 gram,.There is hypertension simultaneously and Urine proteins are preeclampsia.Oedema.
Subjective symptoms: there are the symptoms such as no headache, dim eyesight, uncomfortable in chest, nauseous and vomiting.The appearance of these subjective symptoms indicates progression of the disease
Stage preeclampsia is entered, corresponding check and processing should be done in time.Twitch and stupor: twitch and stupor are that this disease develops to sternly
Weight the stage performance, should medical treatment immediately processing, in due course terminal pregnancy.
The danger that the women of the hypertension of pregnancy or pre-eclampsia suffers from hypertension in the later years will increase, or even always
The probability that it is hospitalized by hypertension related disorders after by 50 years is still very high, and the danger of women's apoplexy of history of pre-eclampsia is
4 times of blood pressure in pregnancy normal women.
Again since antihypertensive drugs can enter fetus by placenta or appear in milk, it is secondary that poison is generated to fetus or baby
Effect.Therefore Chinese medicine is clinically mostly used, but some Chinese Patent Medicines also contain the unfavorable western medicine composition of a certain amount of pair of fetus in fact, it is pregnant
Woman will also be paid close attention to using Chinese patent drug and Chinese herbal medicine decompression.
102670791 A of Chinese patent application CN discloses a kind of alleviation hypertension Cortex Eucommiae traditional Chinese medicine oral liquid, is by following
Made of the bulk pharmaceutical chemicals of parts by weight: 150-300 parts of Cortex Eucommiae, 150-300 parts of Radix Angelicae Sinensis, 150-300 parts of Morinda officinalis, fleece-flower root 150-
300 parts, 150-300 parts of lotus leaf, the oral solution can release rapidly the tinnitus of caused by hypertension, dizzy, headache, shortness of breath and palpitation, mistake
The symptoms such as sleep do not isolate and purify process to effective component but since component is numerous, impurity in traditional Chinese medicinal components and it is harmful at
Dividing effectively to exclude.
103750156 A of Chinese patent application CN disclose it is a kind of using folium cortex eucommiae, low cost, rich in Geniposidic acid,
Aucubin isoreactivity substance is also enriched in the nutriments such as amino acid, glucose, and can reduce the vermicelli processing side of gutta-percha
Method, can apply to prevention and diet in, but its treatment the hypertension of pregnancy effect in terms of it still needs further improvement.
Summary of the invention
To overcome the above technical problem, the present invention provides a kind of eucommia ulmoides extracts composition for treating the hypertension of pregnancy,
The composition can effectively treat the hypertension of pregnancy, and preparation method is simple and efficient, and can effectively improve the purity of effective component, reduce
Impurity content reduces side effect.
In order to achieve the above object, technical solution provided by the invention is as follows:
A kind of eucommia ulmoides extracts composition for treating the hypertension of pregnancy, in parts by weight, the composition includes: bear
20-40 parts of tartaric acid, 10-25 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside mixed extract 20-
60 parts, 30-50 parts of general flavone.
Preferably, in parts by weight, the composition includes: 25-30 parts of ursolic acid, 15-20 parts of chlorogenic acid, rosin
35-45 parts of 30-50 parts of mixed extract, the general flavone of alcohol diglucoside and syringaresinol diglucoside.
Another object of the present invention is to provide the preparation sides of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy
Method, comprising the following steps:
(1) it takes Cortex Eucommiae to crush, is added to the water, digest, filtering obtains enzymolysis liquid and filter residue 1；
(2) filter residue 1 is taken, after petroleum ether, is placed in cold ethyl alcohol, ultrasound, filtering obtains alcoholic solution 1, to alcoholic solution 1
Middle addition water, the solid of precipitation are ursolic acid；
(3) enzymolysis liquid is successively adsorbed through XDA-1 type macroreticular resin, S-8 type macroporous absorbent resin；XDA-1 after absorption
Type macroreticular resin is concentrated through ethanol elution, dry, obtains chlorogenic acid；
S-8 type macroporous absorbent resin after absorption is concentrated through ethanol elution, dry, obtains Pinoresinol diglucoside and fourth
The mixed extract of face cream element diglucoside；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, aqueous solution, the glucan salt that polyethylene glycol is sequentially added into mixed solution are water-soluble
Liquid adjusts pH value, stirs, and stands, after layering, takes lower layer's solution, is concentrated, and is added in ethyl alcohol and is stripped, obtains alcoholic solution 2, will
Alcoholic solution 2 is concentrated, is drying to obtain general flavone；
(5) mixing of gained ursolic acid, chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside is extracted
Object, general flavone, which are dissolved in ethyl alcohol, adds lecithin to get eucommia ulmoides extracts composition.
Preferably, in step (1), the mesh number of the crushing is 20-40 mesh；
Preferably, in step (1), the dosage that water is added is 5-8 times of Cortex Eucommiae quality；
Preferably, in step (1), the enzymatic hydrolysis enzyme are as follows: the mixture of cellulase and poly- methyl galacturonate enzyme；
Preferably, the mass ratio of the cellulase and poly- methyl galacturonate enzyme is 1:1-3；
Preferably, in step (2), the temperature of the cold ethyl alcohol is 1-10 DEG C；
Preferably, in step (2), the temperature of the ultrasound and filtering is no more than 10 DEG C；
Preferably, in step (2), the dosage of the ethyl alcohol is 5-8 times of 1 mass of filter residue.
Preferably, in step (4), the molecular weight of the polyethylene glycol is M=1500-3000；Preferably 2000；
Preferably, in step (4), the concentration of the Aqueous Solutions of Polyethylene Glycol is 30-40%；
Preferably, in step (4), it is total that the additional amount of the Aqueous Solutions of Polyethylene Glycol is that polyethylene glycol accounts for alcohol water mixed solution
The 5-6% of quality；
Preferably, in step (4), the molecular weight of the glucan is M=40000-50000；Preferably M=45000；
Preferably, in step (4), the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline
It is prepared；The glucan concentration of the glucan saline solution is 20-30%；
Preferably, in step (4), the additional amount of the glucan saline solution is that glucan accounts for the total matter of alcohol water mixed solution
The 3-4% of amount；
Preferably, in step (4), the pH value is 6-7；Preferably pH value is 6；
Preferably, in step (4), the stirring carries out at 40-50 DEG C.
The object of the invention is also to provide the treatment hypertension of pregnancy eucommia ulmoides extracts compositions or the Cortex Eucommiae to mention
Take application of the preparation method of compositions in preparation treatment hypertension of pregnancy drug.
Preferably, the treatment hypertension of pregnancy drug is tablet, capsule, pill, the mouth of eucommia ulmoides extracts composition
Take any one of liquid or syrup.
Compared with the prior art, the technical advantages of the present invention are that:
(1) several effective components in eucommia ulmoides extracts are applied by selection in the present invention, be effectively made pregnant to treating
Hypertension of being pregnent has the eucommia ulmoides extracts composition of good therapeutic effect, reduces side effect；
(2) by processes such as step by step arithmetic, purifying, by macroporous absorbent resin respectively by active ingredient chlorogenic acid, rosin
The mixed extract of alcohol diglucoside and syringaresinol diglucoside prepares, and improves its purity；It again will be remaining
Component sequentially adds the aqueous solution of polyethylene glycol, glucan saline solution in system, by the abstraction technique of aqueous two-phase, by it
In general flavone extract, later, general flavone has been further purified after extracting；So that the impurity in entire composition subtracts
It is few；Improve the purity of eucommia ulmoides extracts；
(3) in general flavone extraction process, dosage, pH value and the temperature value of polyethylene glycol and glucan have its recovery rate
There is large effect, by rationally controlling each conditions, acts synergistically, preferably could effectively extract general flavone；
The variation of single factors is likely to cause the variation of general flavone extraction effect, and recovery rate is made to be greatly reduced or increase flavones
In impurity content；Dosage, pH value and the temperature values of the polyethylene glycol and glucan that provide in the present invention are interior can be preferably
The extraction effect of general flavone is played, impurity is reduced, improves its curative effect in the hypertension of pregnancy.
(4) residual components in Cortex Eucommiae after separating-purifying can be also used for preparing other drugs, improve the medicine of Cortex Eucommiae
With value, and the resource for treasuring medicinal material is saved, has reduced waste.
Specific embodiment
Embodiment 1
The eucommia ulmoides extracts composition of the hypertension of pregnancy, in parts by weight, the composition are treated in the present embodiment
It include: the mixed extract 50 of 25 parts of ursolic acid, 15 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside
Part, 35 parts of general flavone；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, comprising the following steps:
(1) take Cortex Eucommiae to be crushed to 30 mesh, be added in 7 times of Cortex Eucommiae quality of water, use mass ratio be the cellulase of 1:2 with
The mixture of poly- methyl galacturonate enzyme digests, and filtering obtains enzymolysis liquid and filter residue 1；
(2) filter residue 1 is taken, after petroleum ether, is placed in its 6 times 2 DEG C cold ethyl alcohol, it is ultrasonic at same temperature,
Filtering, obtains alcoholic solution 1, water is added into alcoholic solution 1, the solid of precipitation is ursolic acid；
(3) enzymolysis liquid is successively adsorbed through XDA-1 type macroreticular resin, S-8 type macroporous absorbent resin；XDA-1 after absorption
Type macroreticular resin is concentrated through ethanol elution, dry, obtains chlorogenic acid；
S-8 type macroporous absorbent resin after absorption is concentrated through ethanol elution, dry, obtains Pinoresinol diglucoside and fourth
The mixed extract of face cream element diglucoside；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, and polyethylene glycol (M=2000) water that concentration is 35% is sequentially added into mixed solution
Solution (Aqueous Solutions of Polyethylene Glycol is added in account for alcohol water mixed solution gross mass according to the amount of polyethylene glycol 6%), glucan (M=
45000) saline solution (glucan saline solution is added in account for alcohol water mixed solution gross mass according to glucan 3%), adjusts pH
Value stirs at 45 DEG C to 6, stands, after layering, take lower layer's solution, be concentrated, it is to be taken out in 35% ethyl alcohol that mass concentration, which is added,
It mentions, obtains alcoholic solution 2, it is alcoholic solution 2 is concentrated, be drying to obtain general flavone；
Wherein, the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline to be prepared；Institute
The glucan concentration for stating glucan saline solution is 25%；
(5) mixing of gained ursolic acid, chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside is extracted
Object, general flavone, which are dissolved in ethyl alcohol, adds lecithin to get eucommia ulmoides extracts composition.
Embodiment 2
The eucommia ulmoides extracts composition of the hypertension of pregnancy, in parts by weight, the composition are treated in the present embodiment
It include: the mixed extract 60 of 40 parts of ursolic acid, 10 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside
Part, 30 parts of general flavone；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, comprising the following steps:
(1) it takes Cortex Eucommiae to be crushed to 20 mesh, is added in 5 times of Cortex Eucommiae quality of water, using 1:1 cellulase and poly- methyl gala
The mixture of uronic acid enzyme digests, and filtering obtains enzymolysis liquid and filter residue 1；
(2) filter residue 1 is taken, after petroleum ether, is placed in its 5 times 1 DEG C cold ethyl alcohol, it is ultrasonic at same temperature,
Filtering, obtains alcoholic solution 1, water is added into alcoholic solution 1, the solid of precipitation is ursolic acid；
(3) enzymolysis liquid is successively adsorbed through XDA-1 type macroreticular resin, S-8 type macroporous absorbent resin；XDA-1 after absorption
Type macroreticular resin is concentrated through ethanol elution, dry, obtains chlorogenic acid；
S-8 type macroporous absorbent resin after absorption is concentrated through ethanol elution, dry, obtains Pinoresinol diglucoside and fourth
The mixed extract of face cream element diglucoside；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, and polyethylene glycol (M=1500) water that concentration is 30% is sequentially added into mixed solution
Solution (Aqueous Solutions of Polyethylene Glycol is added in account for alcohol water mixed solution gross mass according to the amount of polyethylene glycol 5%), glucan (M=
40000) saline solution (glucan saline solution is added in account for alcohol water mixed solution gross mass according to glucan 4%), adjusts pH
Value stirs at 40 DEG C to 7, stands, after layering, take lower layer's solution, be concentrated, it is to be taken out in 30% ethyl alcohol that mass concentration, which is added,
It mentions, obtains alcoholic solution 2, it is alcoholic solution 2 is concentrated, be drying to obtain general flavone；
Wherein, the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline to be prepared；Institute
The glucan concentration for stating glucan saline solution is 20%；
(5) mixing of gained ursolic acid, chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside is extracted
Object, general flavone, which are dissolved in ethyl alcohol, adds lecithin to get eucommia ulmoides extracts composition.
Embodiment 3
The eucommia ulmoides extracts composition of the hypertension of pregnancy, in parts by weight, the composition are treated in the present embodiment
It include: the mixed extract 20 of 20 parts of ursolic acid, 25 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside
Part, 50 parts of general flavone；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, comprising the following steps:
(1) it takes Cortex Eucommiae to be crushed to 40 mesh, is added in 8 times of Cortex Eucommiae quality of water, using 1:3 cellulase and poly- methyl gala
The mixture of uronic acid enzyme digests, and filtering obtains enzymolysis liquid and filter residue 1；
(2) filter residue 1 is taken, after petroleum ether, is placed in its 8 times 10 DEG C cold ethyl alcohol, it is ultrasonic at same temperature,
Filtering, obtains alcoholic solution 1, water is added into alcoholic solution 1, the solid of precipitation is ursolic acid；
(3) enzymolysis liquid is successively adsorbed through XDA-1 type macroreticular resin, S-8 type macroporous absorbent resin；XDA-1 after absorption
Type macroreticular resin is concentrated through ethanol elution, dry, obtains chlorogenic acid；
S-8 type macroporous absorbent resin after absorption is concentrated through ethanol elution, dry, obtains Pinoresinol diglucoside and fourth
The mixed extract of face cream element diglucoside；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, and polyethylene glycol (M=3000) water that concentration is 40% is sequentially added into mixed solution
Solution (Aqueous Solutions of Polyethylene Glycol is added in account for alcohol water mixed solution gross mass according to the amount of polyethylene glycol 6%), glucan (M=
50000) saline solution (glucan saline solution is added in account for alcohol water mixed solution gross mass according to glucan 3%), adjusts pH
Value stirs at 50 DEG C to 6, stands, after layering, take lower layer's solution, be concentrated, it is to be taken out in 40% ethyl alcohol that mass concentration, which is added,
It mentions, obtains alcoholic solution 2, it is alcoholic solution 2 is concentrated, be drying to obtain general flavone；
Wherein, the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline to be prepared；Institute
The glucan concentration for stating glucan saline solution is 30%；
(5) mixing of gained ursolic acid, chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside is extracted
Object, general flavone, which are dissolved in ethyl alcohol, adds lecithin to get eucommia ulmoides extracts composition.
Embodiment 4
The eucommia ulmoides extracts composition of the hypertension of pregnancy, in parts by weight, the composition are treated in the present embodiment
Include:
The mixing of 30 parts of ursolic acid, 20 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside is extracted
30 parts of object, 45 parts of general flavone.
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, comprising the following steps:
(1) it takes Cortex Eucommiae to be crushed to 20 mesh, is added in 6 times of Cortex Eucommiae quality of water, using 1:2 cellulase and poly- methyl gala
The mixture of uronic acid enzyme digests, and filtering obtains enzymolysis liquid and filter residue 1；
(2) filter residue 1 is taken, after petroleum ether, is placed in its 6 times 5 DEG C cold ethyl alcohol, it is ultrasonic at same temperature,
Filtering, obtains alcoholic solution 1, water is added into alcoholic solution 1, the solid of precipitation is ursolic acid；
(3) enzymolysis liquid is successively adsorbed through XDA-1 type macroreticular resin, S-8 type macroporous absorbent resin；XDA-1 after absorption
Type macroreticular resin is concentrated through ethanol elution, dry, obtains chlorogenic acid；
S-8 type macroporous absorbent resin after absorption is concentrated through ethanol elution, dry, obtains Pinoresinol diglucoside and fourth
The mixed extract of face cream element diglucoside；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, and polyethylene glycol (M=2000) water that concentration is 30% is sequentially added into mixed solution
Solution (Aqueous Solutions of Polyethylene Glycol is added in account for alcohol water mixed solution gross mass according to the amount of polyethylene glycol 5%), glucan (M=
40000) saline solution (glucan saline solution is added in account for alcohol water mixed solution gross mass according to glucan 3%), adjusts pH
Value stirs at 50 DEG C to 6, stands, after layering, take lower layer's solution, be concentrated, it is to be taken out in 40% ethyl alcohol that mass concentration, which is added,
It mentions, obtains alcoholic solution 2, it is alcoholic solution 2 is concentrated, be drying to obtain general flavone；
Wherein, the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline to be prepared；Institute
The glucan concentration for stating glucan saline solution is 20%；
(5) mixing of gained ursolic acid, chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside is extracted
Object, general flavone, which are dissolved in ethyl alcohol, adds lecithin to get eucommia ulmoides extracts composition.
Comparative example 1
Compared with Example 1, difference is only that the composition weight number of composition is different；
The eucommia ulmoides extracts composition of the hypertension of pregnancy, in parts by weight, the composition are treated in the present embodiment
It include: the mixed extract 70 of 15 parts of ursolic acid, 15 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside
Part, 25 parts of general flavone；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, with embodiment 1.
Comparative example 2
Compared with Example 1, difference is only that the composition weight number of composition is different；
The eucommia ulmoides extracts composition of the hypertension of pregnancy, in parts by weight, the composition are treated in the present embodiment
It include: the mixed extract 50 of 5 parts of ursolic acid, 15 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside
Part, 55 parts of general flavone；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, with embodiment 1.
Comparative example 3
Compared with Example 1, difference is only that in the extraction process of effective component that pH value is different.
The eucommia ulmoides extracts composition of the hypertension of pregnancy is treated in the present embodiment, each component parts by weight are the same as embodiment 1；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, comprising the following steps:
(1)-(3) are the same as (1)-(3) the step of embodiment 1；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, and polyethylene glycol (M=2000) water that concentration is 35% is sequentially added into mixed solution
Solution (Aqueous Solutions of Polyethylene Glycol is added in account for alcohol water mixed solution gross mass according to the amount of polyethylene glycol 6%), glucan (M=
45000) saline solution (glucan saline solution is added in account for alcohol water mixed solution gross mass according to glucan 3%), adjusts pH
Value stirs at 45 DEG C to 3, stands, after layering, take lower layer's solution, be concentrated, it is to be taken out in 35% ethyl alcohol that mass concentration, which is added,
It mentions, obtains alcoholic solution 2, it is alcoholic solution 2 is concentrated, be drying to obtain general flavone；
Wherein, the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline to be prepared；Institute
The glucan concentration for stating glucan saline solution is 25%；
(5) with (5) the step of embodiment 1.
Comparative example 4
Compared with Example 1, difference is only that in the extraction process of effective component that pH value is different.
The eucommia ulmoides extracts composition of the hypertension of pregnancy is treated in the present embodiment, each component parts by weight are the same as embodiment 1；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, comprising the following steps:
(1)-(3) are the same as (1)-(3) the step of embodiment 1；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, and polyethylene glycol (M=2000) water that concentration is 35% is sequentially added into mixed solution
Solution (Aqueous Solutions of Polyethylene Glycol is added in account for alcohol water mixed solution gross mass according to the amount of polyethylene glycol 6%), glucan (M=
45000) saline solution (glucan saline solution is added in account for alcohol water mixed solution gross mass according to glucan 3%), adjusts pH
Value stirs at 45 DEG C to 9, stands, after layering, take lower layer's solution, be concentrated, it is to be taken out in 35% ethyl alcohol that mass concentration, which is added,
It mentions, obtains alcoholic solution 2, it is alcoholic solution 2 is concentrated, be drying to obtain general flavone；
Wherein, the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline to be prepared；Institute
The glucan concentration for stating glucan saline solution is 25%；
(5) with (5) the step of embodiment 1.
Comparative example 5
Compared with Example 1, difference is only that the dosage of polyethylene glycol and glucan is not in the extraction process of effective component
Together.
The eucommia ulmoides extracts composition of the hypertension of pregnancy is treated in the present embodiment, each component parts by weight are the same as embodiment 1；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, comprising the following steps:
(1)-(3) are the same as (1)-(3) the step of embodiment 1；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, and polyethylene glycol (M=2000) water that concentration is 35% is sequentially added into mixed solution
Solution (Aqueous Solutions of Polyethylene Glycol is added in account for alcohol water mixed solution gross mass according to the amount of polyethylene glycol 3%), glucan (M=
45000) saline solution (glucan saline solution is added in account for alcohol water mixed solution gross mass according to glucan 6%), adjusts pH
Value stirs at 45 DEG C to 6, stands, after layering, take lower layer's solution, be concentrated, it is to be taken out in 35% ethyl alcohol that mass concentration, which is added,
It mentions, obtains alcoholic solution 2, it is alcoholic solution 2 is concentrated, be drying to obtain general flavone；
Wherein, the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline to be prepared；Institute
The glucan concentration for stating glucan saline solution is 25%；
(5) with (5) the step of embodiment 1.
Comparative example 6
Compared with Example 1, difference is only that the dosage of polyethylene glycol and glucan is not in the extraction process of effective component
Together.
The eucommia ulmoides extracts composition of the hypertension of pregnancy is treated in the present embodiment, each component parts by weight are the same as embodiment 1；
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy, comprising the following steps:
(1)-(3) are the same as (1)-(3) the step of embodiment 1；
(4) it will be precipitated in step (2) remaining after macroporous resin adsorption in remaining alcoholic solution and step (3) after solid
Enzymolysis liquid mixing, obtains alcohol water mixed solution, and polyethylene glycol (M=2000) water that concentration is 35% is sequentially added into mixed solution
Solution (Aqueous Solutions of Polyethylene Glycol is added in account for alcohol water mixed solution gross mass according to the amount of polyethylene glycol 3%), glucan (M=
45000) saline solution (glucan saline solution is added in account for alcohol water mixed solution gross mass according to glucan 3%), adjusts pH
Value stirs at 45 DEG C to 6, stands, after layering, take lower layer's solution, be concentrated, it is to be taken out in 35% ethyl alcohol that mass concentration, which is added,
It mentions, obtains alcoholic solution 2, it is alcoholic solution 2 is concentrated, be drying to obtain general flavone；
Wherein, the preparation method of the glucan saline solution is that glucan is dissolved in physiological saline to be prepared；Institute
The glucan concentration for stating glucan saline solution is 25%；
(5) with (5) the step of embodiment 1.
Effect example
SD rat, 240-280g, SPF grade are provided by Jiangning county Qinglongshan animal reproduction field；
L-NAME (L-NAME) physiological saline solution, final concentration of 0.05g/ml；
Being suspended with 0.5%CMC-Na for embodiment 1-4 and comparative example 1-6 is dissolved, final concentration of 0.1g/ml；
Rat adaptive feeding is after a week mated female rats and male rat three days by the ratio of 2:1, with discovery
Vaginal plug or introitus obviously open redness and are denoted as gestation first day, reject to the pregnant female mice that will not be pregnant for 9th day, take success
The female rats of pregnancy 120 are divided into 12 groups, respectively blank control group, model group, embodiment 1-4 group and comparative example 1-6
Group, the 10th day starts to be administered, and measures the blood pressure (blood pressure is repeatedly measurement, is averaged) that preceding pregnant rat is administered, blank control
Group feeding physiological saline 0.5g/kg, remaining each group inject modeling agent L-NAME according to 0.25g/kg daily, and modeling group fills wherein one
The physiological saline of group stomach-filling 0.5g/kg, remaining each group are suspended according to made of 0.5g/kg stomach-filling embodiment 1-4 and comparative example 1-6
Liquid；Blood pressure after the administration of measurement in 19th day, takes blood after measurement, anaesthetize, and puts to death, and dissection takes placenta.
(1) administration front and back rat blood index variation (table 1)
The rat blood index variation of the administration of table 1 front and back (N=10)
| Test group | Blood viscosity (cp) | Blood flow (ml/min) |
| Blank control group | 3.81±0.62a | 7.24±1.13d |
| Hypertension model group | 5.53±0.81c | 3.56±0.54f |
| Embodiment 1 | 4.12±0.72a | 5.52±0.47e |
| Embodiment 2 | 4.09±1.03a | 5.74±0.69e |
| Embodiment 3 | 4.21±0.55a | 5.38±0.85e |
| Embodiment 4 | 4.15±0.61a | 5.59±0.76e |
| Comparative example 1 | 4.73±1.23b | 4.35±1.25f |
| Comparative example 2 | 4.91±0.93b | 4.12±1.04f |
| Comparative example 3 | 4.67±0.77b | 4.26±0.69f |
| Comparative example 4 | 4.86±1.31b | 4.54±0.77f |
| Comparative example 5 | 5.13±1.28c | 3.92±0.96f |
| Comparative example 6 | 5.34±0.88c | 4.06±1.11f |
Note: in same row, P < 0.05 between different letters；
By experimental data it is found that hypertension model group is compared with blank control group, blood viscosity is significantly raised, and blood flow is obvious
It reduces, illustrates modeling success, the experiment of embodiment 1-4 is it is found that eucommia ulmoides extracts of the invention have preferably pregnant high viscosity
Inhibitory effect, and blood flow can be improved；
By the experimental data of comparative example 1-6 it is found that the proportion of each effective component, the extraction process of effective component in the present invention
In design parameter to the drug effect of eucommia ulmoides extracts have significant impact.
(2) influence (table 2) of the eucommia ulmoides extracts to preeclampsia rat mean arterial pressure
The rat mean arterial pressure variation of the administration of table 2 front and back (N=10)
| Test group | Before administration (mmHg) | After administration (mmHg) |
| Blank control group | 105.6±8.9 | 109.3±9.4a |
| Hypertension model group | 103.7±10.4 | 142.7±3.3b |
| Embodiment 1 | 106.2±7.2 | 114.2±9.1a |
| Embodiment 2 | 108.1±10.1 | 115.3±5.2a |
| Embodiment 3 | 106.5±9.6 | 112.8±11.3a |
| Embodiment 4 | 107.2±5.7 | 113.5±6.7a |
| Comparative example 1 | 105.4±6.4 | 126.5±13.2c |
| Comparative example 2 | 106.9±9.2 | 122.3±9.4c |
| Comparative example 3 | 108.4±13.1 | 127.5±11.4c |
| Comparative example 4 | 107.5±8.6 | 123.6±7.6c |
| Comparative example 5 | 107.9±5.3 | 130.1±10.8c |
| Comparative example 6 | 108.6±11.5 | 135.5±16.4c |
Note: in same row, P < 0.05 between different letters；
By experimental data it is found that before administration, rat mean arterial pressure does not have significant difference；After administration, hypertension mould
For type group compared with blank control group, blood pressure is significantly raised, illustrates modeling success, and embodiment 1-4's tests Du it is found that of the invention
Secondary extract has preferable inhibitory effect to the hypertension of pregnancy；
By the experimental data of comparative example 1-6 it is found that the proportion of each effective component, the extraction process of effective component in the present invention
In design parameter to the drug effect of eucommia ulmoides extracts have significant impact.
Above-mentioned detailed description is illustrating for one of them possible embodiments of the present invention, the embodiment not to
The scope of the patents of the invention is limited, all equivalence enforcements or change without departing from carried out by the present invention are intended to be limited solely by the technology of the present invention
In the range of scheme.
Claims (10)
1. a kind of eucommia ulmoides extracts composition for treating the hypertension of pregnancy, in parts by weight, the composition includes: black bearberry
The mixed extract 20-60 of 20-40 parts sour, 10-25 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside
Part, 30-50 parts of general flavone.
2. the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy as described in claim 1, which is characterized in that according to parts by weight
Number meter, the composition includes: 25-30 parts of ursolic acid, 15-20 parts of chlorogenic acid, Pinoresinol diglucoside and syringaresinol two
35-45 parts of 30-50 parts of mixed extract, the general flavone of glucoside.
3. the preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy as described in claim 1 or 2 is any, including
Following steps:
(1) it takes Cortex Eucommiae to crush, is added to the water, digest, filtering obtains enzymolysis liquid and filter residue 1；
(2) filter residue 1 is taken, after petroleum ether, is placed in cold ethyl alcohol, ultrasound, filtering obtains alcoholic solution 1, adds into alcoholic solution 1
Enter water, the solid of precipitation is ursolic acid；
(3) enzymolysis liquid is successively adsorbed through XDA-1 type macroreticular resin, S-8 type macroporous absorbent resin；XDA-1 type after absorption is big
Hole resin is concentrated through ethanol elution, dry, obtains chlorogenic acid；S-8 type macroporous absorbent resin after absorption is concentrated through ethanol elution,
It is dry, obtain the mixed extract of Pinoresinol diglucoside and syringaresinol diglucoside；
(4) through macroporous resin adsorption after remaining enzymatic hydrolysis will be precipitated after solid in remaining alcoholic solution and step (3) in step (2)
Liquid mixing, obtains alcohol water mixed solution, aqueous solution, the glucan saline solution of polyethylene glycol is sequentially added into mixed solution, adjusts
PH value is saved, is stirred, stands, after layering, takes lower layer's solution, is concentrated, is added in ethyl alcohol and is stripped, alcoholic solution 2 is obtained, by alcoholic solution
It is 2 concentrated, be drying to obtain general flavone；
(5) by the mixed extract of gained ursolic acid, chlorogenic acid, Pinoresinol diglucoside and syringaresinol diglucoside,
General flavone, which is dissolved in ethyl alcohol, adds lecithin to get eucommia ulmoides extracts composition.
4. the preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy as claimed in claim 3, which is characterized in that
In step (1), the mesh number of the crushing is 20-40 mesh；The dosage that water is added is 5-8 times of Cortex Eucommiae quality.
5. the preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy as claimed in claim 3, which is characterized in that
In step (1), the enzymatic hydrolysis enzyme are as follows: the mixture of cellulase and poly- methyl galacturonate enzyme；The cellulase and
The mass ratio of poly- methyl galacturonate enzyme is 1:1-3.
6. the preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy as claimed in claim 3, which is characterized in that
In step (2), the temperature of the cold ethyl alcohol is 1-10 DEG C；The ultrasound and the temperature of filtering are no more than 10 DEG C.
7. the preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy as claimed in claim 3, which is characterized in that
In step (2), the dosage of the ethyl alcohol is 5-8 times of 1 mass of filter residue.
8. the preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy as claimed in claim 3, which is characterized in that
In step (4), the molecular weight of the polyethylene glycol is M=1500-3000；The additional amount of the Aqueous Solutions of Polyethylene Glycol is poly- second
Glycol accounts for the 5-6% of alcohol water mixed solution gross mass；
The molecular weight of the glucan is M=40000-50000；The additional amount of the glucan saline solution is that glucan accounts for alcohol
The 3-4% of water mixed solution gross mass.
9. the preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy as claimed in claim 3, which is characterized in that
In step (4), the pH value is 6-7；The stirring carries out at 40-50 DEG C.
10. the eucommia ulmoides extracts composition or the claim 3-9 that treat the hypertension of pregnancy as described in claim 1-2 is any are any
The preparation method of the eucommia ulmoides extracts composition of the treatment hypertension of pregnancy answering in preparation treatment hypertension of pregnancy drug
With.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910896111.8A CN110496148B (en) | 2019-09-22 | 2019-09-22 | Eucommia ulmoides extract composition for treating gestational hypertension and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910896111.8A CN110496148B (en) | 2019-09-22 | 2019-09-22 | Eucommia ulmoides extract composition for treating gestational hypertension and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110496148A true CN110496148A (en) | 2019-11-26 |
| CN110496148B CN110496148B (en) | 2021-04-30 |
Family
ID=68592396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910896111.8A Active CN110496148B (en) | 2019-09-22 | 2019-09-22 | Eucommia ulmoides extract composition for treating gestational hypertension and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110496148B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113413392A (en) * | 2021-07-07 | 2021-09-21 | 江西普正制药股份有限公司 | Eucommia ulmoides extract composition and preparation method and application thereof |
-
2019
- 2019-09-22 CN CN201910896111.8A patent/CN110496148B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| 彭红梅等: "杜仲颗粒结合常规疗法治疗妊娠期高血压疾病的临床疗效", 《重庆医学》 * |
| 彭胜等: "双水相体系萃取分离杜仲黄酮", 《中药材》 * |
| 杜仲综合利用技术国家地方联合工程实验室: "杜仲的化学成分与功能", 《HTTPS://DUZHONG.JSU.EDU.CN/INFO/1017/1169.HTM》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113413392A (en) * | 2021-07-07 | 2021-09-21 | 江西普正制药股份有限公司 | Eucommia ulmoides extract composition and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110496148B (en) | 2021-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100534474C (en) | Medicine composition for enhancing immunity, and its preparation method and use | |
| CN101428086B (en) | Traditional Chinese medicine preparation for treating peptic ulcer and preparation method thereof | |
| CN102205107B (en) | Chinese medicinal preparation for treating duodenal ulcer and preparation method thereof | |
| CN109646471A (en) | A kind of activation notoginsenoside rich in rare ginsenoside is in the application prepared in oral care product | |
| CN110496148A (en) | A kind of eucommia ulmoides extracts composition that treating the hypertension of pregnancy and its application | |
| CN103341074A (en) | Application of Yixuanning granules in preparation of medicaments for treating insomnia | |
| CN104337927A (en) | Calyx seu fructus physalis extractive, medicine composition and/or functional food | |
| CN102784230B (en) | Pharmaceutical composition preparation for treating nutritional anemia | |
| CN105012770A (en) | Health drink and preparation method thereof | |
| CN108902989A (en) | A kind of auxiliary improves the ginseng peptide and preparation method thereof of cardiovascular and cerebrovascular disease | |
| CN100500174C (en) | Medicine composition used for lowering blood-sugar, preparation method and use thereof | |
| CN105055851A (en) | Chinese medicinal composition for treatment of diabetes, preparation and application thereof | |
| CN114468291A (en) | Inositol composition for improving female infertility and preparation method thereof | |
| CN110623993A (en) | Compound nutritional tablet of traditional Chinese medicine composition for treating gynecological inflammation and preparation method thereof | |
| CN107468849A (en) | A kind of medicine for treating chronic renal failure and preparation method thereof | |
| CN108721353A (en) | A kind of preparation method of Radix Notoginseng oral solution | |
| CN107811907A (en) | A kind of body lotion for promoting subcutaneous fat to decompose | |
| CN116942771B (en) | Traditional Chinese medicine composition for treating coronary heart disease and application thereof | |
| CN113521186B (en) | Hypoglycemic drug and preparation method and application thereof | |
| CN102579801B (en) | Traditional Chinese medicine preparation for treating diabetic syndrome and preparation method of same | |
| CN107137456A (en) | It is a kind of to treat medicine of chronic osteomyelitis and its preparation method and application | |
| CN101040977B (en) | Medicine for treating prostate disease and method for preparing same | |
| CN104225014B (en) | A kind of Tibetan medicine for the treatment of diabetes | |
| CN105168430A (en) | Medicine composition for preventing and treating gout and preparation method thereof | |
| CN105250919B (en) | It is a kind of for preventing and/or the Chinese medicine composition for treating liver disease and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |