CN105748409A - Protopanoxadiol submicroemulsion preparation as well as preparation method and application thereof - Google Patents
Protopanoxadiol submicroemulsion preparation as well as preparation method and application thereof Download PDFInfo
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- 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
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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Abstract
The invention provides a protopanoxadiol submicroemulsion preparation and a preparation method thereof. The protopanoxadiol submicroemulsion preparation comprises protopanoxadiol, oil, an emulsifier and a co-emulsifier, average particle size of the protopanoxadiol submicroemulsion preparation is 110-130nm, and Zeta potential ranges from -40mV to -20mV. The invention also provides an application of the protopanoxadiol submicroemulsion preparation in preparation of a medicine with the effects of promoting hematopoietic cell proliferation and alleviating bone marrow inhibiting effect caused by tumour treatment.
Description
Technical field
The present invention relates to a kind of protopanoxadiol Submicron Emulsion preparation and its production and use, belong to pharmaceutical preparation neck
Territory.
Background technology
Protopanoxadiol (PPD) is diol type ginsengenin, is mainly derived from the Araliaceaes such as ginseng, American Ginseng, pseudo-ginseng
Plant.It is the aglycon of glycol group ginsenoside, is also glycol group ginsenoside end product after microorganism glycolysis.Research table
The sodium channel that bright PPD has suppression kinds of tumors growth, antidepression, activation chloride channel, suppression to be activated depolarizes, suppression people
Many activity such as the growth of embryonic kidney cell HEK-293 cell and growth of H. pylori.Meanwhile, cerebral damage is had by PPD
Protective effect.
PPD is lipophilic compound, and in water, dissolubility is poor, and oral administration biaavailability is low, and the half-life is short.Need protoplast
The preparation of ginseng glycol carries out studying to improve bioavilability.The researchs such as hair Jingjing are prepared for PPD dry suspensoid agent, and this formulation is improved
Drug absorption, and do not affected by food, particle is big at intestines and stomach distribution areas, absorbs fast, and bioavilability is carried
Height (sees a mao Jingjing, Zhang Tong, Wang Bing etc..The prescription of 20 (S)-protopanoxadiol dry suspensoid agents and preliminary quality research.Middle one-tenth
Medicine, 2013,34 (9): 1680-1684).Jin Shengxuan etc. are prepared for PPD liposome for intravenous injection, pass to realizing targeting
Medicine, plays antitumor action and (sees Jin Shengxuan, Lei Rongjian, Sun Jingyun.HPLC measures containing of 20 (s)-Protopanaxadiol liposome
Amount and envelop rate.Nanjing University of Traditional Chinese Medicine's journal, 2009,25 (3): 197-198).Jin Xin etc. are prepared for the protoplast of PPD and join lipid
Cubic liquid crystal nanoparticle, lipid cubic liquid crystal by polar lipid in aqueous environment by adsorb quantitative water formed have special
The gellike of internal structure cube skeleton structure mutually, has stronger adhesiveness, thus promotes that medicine cross-film absorbs.Preparation is set up
After side's liquid crystal, adding the medicine holdup time in vivo, Relative oral bioavailability is 1.66 times of bulk drug and (sees gold
Prosperous, Zhang Zhenhai, Sun E etc., protopanoxadiol lipid-based cubic liquid crystalline nanoparticle pharmacokinetic studies in rat body.Chinese medicine
Magazine, 2013,38 (2): 263-268).Drug carrier passed by emulsion can increase solubility and the stability of insoluble drug, oil
Phase and emulsifying agent can degrade and absorb in vivo, and stable in properties does not produce superman's body standard osmotic pressure after intravenous.Warp of the present invention
Patent consulting and literature search, the most not yet find PPD is prepared as emulsion for injection, carry out the report of antitumor research.
Summary of the invention
It is an object of the present invention to provide a kind of protopanoxadiol Submicron Emulsion preparation；
Second object of the present invention is to provide the preparation method of this protopanoxadiol Submicron Emulsion preparation；
Third object of the present invention is to provide the Submicron Emulsion preparation prepared by protopanoxadiol and the present invention in preparation
There is the application in the medicine promoting hematopoietic cell proliferation, alleviation bone marrow inhibition.
A kind of protopanoxadiol Submicron Emulsion preparation, including protopanoxadiol, oil, emulsifying agent, assistant for emulsifying agent, its average grain diameter
Being 110～130nm, Zeta potential is-20～-40mV.This protopanoxadiol Submicron Emulsion preparation is through high pressure, centrifugal, dilution process
The most moderately good, in 4,20,30 DEG C of stability tests 4 months, have good stability.
In some embodiments, described protopanoxadiol content is 0.1-0.5%, oil phase content 10-30%, emulsifying agent
With assistant for emulsifying agent content 3-4%；Preferably, emulsifying agent is 2:1～2 with the ratio of assistant for emulsifying agent；It is further preferred that oil phase contains
Amount is 10%, and emulsifying agent is 2:1.5 with the ratio of assistant for emulsifying agent.
In some embodiments, described grease separation is from vegetable oil, animal oil, mineral oil or artificial oil；Described plant grease separation
Any one or a few in soybean oil, corn oil, peanut oil, olive oil, castor oil, palm oil；Described animal oil is selected from
Fish oil or oleic acid；Described mineral oil is selected from any one or a few in aliphatic hydrocarbon, cerul hydrocarbon, aromatic hydrocarbon or paraffin oil；Described
Artificial oil is selected from linoleic acid, ethyl oleate, rilanit special, hydrogenated groundnut, cotmar, ethyl linoleate, self-emulsifying
Any one or a few in monostearate, pungent/glycerol decanoate, isopropyl myristate or triethylglycerides；Further
Preferably, described oil is soybean oil or peanut oil.
In some embodiments, described emulsifying agent is selected from Fabaceous Lecithin, yolk phospholipid, phosphatidyl-ethanolamine, serine phosphorus
Any one or a few in fat, lipositol, phosphatidic acid；The most described emulsifying agent is egg yolk lecithin or soybean ovum phosphorus
Fat.
In some embodiments, described assistant for emulsifying agent is selected from poloxamer (F68) or solutol.
The preparation method that present invention also offers described protopanoxadiol Submicron Emulsion preparation comprises the steps:
Step 1, the preparation of oil phase: add emulsifying agent and effective dose PPD in appropriate oil, dispersion obtains oil phase；
Step 2, the preparation of aqueous phase: qs glycerin, assistant for emulsifying agent are dissolved in suitable quantity of water, make aqueous phase；
Step 3, just emulsification: under the conditions of 60～70 DEG C, oil phase is added aqueous phase, make colostrum；
Step 4, homogeneous: taking the primary emulsion of step 3 preparation, homogeneous, emulsification, is 110～130nm to emulsion droplet average grain diameter；
Step 5, filling, sterilizing.
In some embodiments, step 3 carries out ultrasonically treated after oil phase adds aqueous phase, and ultrasonic time is 5-60min；
Step 4 homogeneous is carried out in high pressure homogenizer, and homogenization pressure is 500-2000bar, and cycle-index is 5-20 time.Preferably, super
The sound time is 10-20min；Step 4 homogenization pressure is 1000-2000bar, and cycle-index is 5-15 time.It is further preferred that it is super
The sound time is 10min；Homogenization pressure is 2000bar, and cycle of higher pressure number of times is 10 times.
The present invention also provides for protopanoxadiol and has the bone promoting hematopoietic cell proliferation, alleviating oncotherapy generation in preparation
Application in the medicine of marrow inhibitory action.
Internal experiment in vitro all prove protopanoxadiol emulsion for injection can be obviously promoted bone marrow cell grain system (CFU-GM),
Red system (CFU-E/BFU-E) hematopoietic progenitor population generates.Show that protopanoxadiol emulsion for injection has promotion hematopoietic cell
The effect of the bone marrow suppression that propagation, alleviation oncotherapy produce.
Accompanying drawing explanation
Fig. 1 PPD Submicron Emulsion formulation aesthetics form
Form under Fig. 2 PPD Submicron Emulsion preparation transmission electron microscope
Specific embodiment mode
Embodiment 1
Prescription:
Embodiment 2
Embodiment 3
Prescription:
Embodiment 4
Prescription:
Embodiment 5
Prescription:
Embodiment 6
The preparation method of the arbitrary prescription of embodiment 1～5: oil phase (soybean oil or peanut oil) is stirred in 80 DEG C and adds breast
Agent, high speed dispersion, to becoming settled solution, then adds protopanoxadiol at 60 DEG C, and high speed dispersion uniformly obtains oil phase；Separately
Adding 20ml glycerine and assistant for emulsifying agent in 800ml water, 60 DEG C are uniformly mixing to obtain aqueous phase.Under 60 DEG C of high-speed stirred, by oil
Slowly it is added drop-wise to aqueous phase mutually, continues ultrasonic agitation 10 minutes, be settled to 1000ml.By colostrum through high-pressure homogeneous 2000bar pressure
Circulate 10 times, filling, sterilizing, both.
The Submicron Emulsion preparation physical parameter that embodiment 1～5 prescription is prepared by the present embodiment method
Embodiment 7
The preparation method of the arbitrary prescription of embodiment 1～5, substantially the same manner as Example 6, difference is: the ultrasonic agitation time
It it is 15 minutes.
Its average grain diameter of Submicron Emulsion preparation that the present embodiment method prepares is 115～125nm, and Zeta potential is-30
～-40mV.
Embodiment 8
The preparation method of the arbitrary prescription of embodiment 1～5, substantially the same manner as Example 6, difference is: the ultrasonic agitation time
It it is 20 minutes.
Its average grain diameter of Submicron Emulsion preparation that the present embodiment method prepares is 115～125nm, and Zeta potential is-30
～-40mV.
Embodiment 9
The preparation method of the arbitrary prescription of embodiment 1～5, substantially the same manner as Example 6, difference is: high-pressure homogeneous pressure
For 1000bar, high-pressure homogeneous cycle-index is 10.
Its average grain diameter of Submicron Emulsion preparation that the present embodiment method prepares is 115～125nm, and Zeta potential is-30
～-40mV.
Embodiment 10
The preparation method of the arbitrary prescription of embodiment 1～5, substantially the same manner as Example 6, difference is: high-pressure homogeneous pressure
For 700bar, high-pressure homogeneous cycle-index is 15.
Its average grain diameter of Submicron Emulsion preparation that the present embodiment method prepares is 115～125nm, and Zeta potential is-30
～-40mV.
Embodiment 11
The preparation method of the arbitrary prescription of embodiment 1～5, substantially the same manner as Example 6, difference is: first emulsifying temperature is
70℃。
Its average grain diameter of Submicron Emulsion preparation that the present embodiment method prepares is 115～125nm, and Zeta potential is-30
～-40mV.
Embodiment 12
The preparation method of the arbitrary prescription of embodiment 1～5, substantially the same manner as Example 6, difference is: first emulsifying temperature is
40℃。
Its average grain diameter of Submicron Emulsion preparation that the present embodiment method prepares is 230～240nm.
Embodiment 13
The preparation method of the arbitrary prescription of embodiment 1～5, substantially the same manner as Example 6, difference is: first emulsifying temperature is
80℃。
Its average grain diameter of Submicron Emulsion preparation that the present embodiment method prepares is 240～250nm.
Submicron Emulsion preparation stability is investigated:
Test Submicron Emulsion preparation is the Submicron Emulsion preparation that embodiment 1 prescription is prepared by embodiment 6 preparation method.
The sign of Submicron Emulsion:
Proterties: outward appearance presents dispersed, milky Submicron Emulsion preparation, weak blue fluorescence (see Fig. 1) seen from bottle wall.
PH value: PPD Submicron Emulsion between pH value 8.2-8.4, has prepared unpasteurized PPD Submicron Emulsion pH when being prepared as colostrum
Value is between 7.9-8.0, and the PPD Submicron Emulsion pH value after sterilizing is between 7.0-7.2.
Submicron Emulsion morphologic observation: take the appropriate distilled water diluting of Submicron Emulsion to debita spissitudo, dripped by micro emulsion on copper mesh, uses
2% phosphotungstic acid negative staining 1min, with observing the form of emulsion droplet, for black even scattered spherical (see Fig. 2) under transmission electron microscope.
Stability:
1, the autoclaving impact on Submicron Emulsion
Take with a collection of Submicron Emulsion, be divided into 2 parts, and a pressure sterilizing (105 DEG C, 45min；115 DEG C, 30min and 121 DEG C,
15min), a without pressure sterilizing, observe the outward appearance of 2 parts of Submicron Emulsions, compare the change of particle diameter, current potential and medicament contg simultaneously
Change.The results are shown in Table 1.
The impact on PPD Submicron Emulsion of table 1 autoclaving
Result shows PPD Submicron Emulsion stable in physicochemical property after autoclaving.
2, dewatering ability
By Submicron Emulsion three batches, 3500rmp, centrifugal 20min, seen whether that medicine crystal grain separates out, mensuration particle diameter, current potential,
Medicament contg.The results are shown in Table 2.
The dewatering ability of table 2 PPD Submicron Emulsion
The dewatering ability of result display PPD Submicron Emulsion is good.
3, dilution stability
By Submicron Emulsion three batches, after diluting 10,50,100,200,500,1000,2000 times respectively, see whether that medicine is brilliant
Size separation goes out, and measures particle diameter, current potential.The results are shown in Table 3.
The dilution stability of table 3 PPD Submicron Emulsion
| Multiple | Particle diameter (nm) | PDI | Current potential (-mV) |
| 0 | 119.7±0.9 | 0.142±0.022 | -35.6±1.6 |
| 10 | 132.9±0.8 | 0.198±0.019 | -33.5±0.3 |
| 50 | 120.1±1.3 | 0.145±0.021 | -33.4±1.0 |
| 100 | 119.7±0.9 | 0.142±0.022 | -35.6±1.6 |
| 200 | 120.6±1.0 | 0.143±0.009 | -38.8±3.9 |
| 500 | 118.5±0.7 | 0.149±0.024 | -37.6±0.6 |
| 1000 | 120.7±0.3 | 0.154±0.009 | -28.1±0.8 |
| 2000 | 124.4±0.2 | 0.203±0.026 | -23.4±3.7 |
Result display dilution is stable, dilutes 2000 times of change of size still less than 5%.
4, PPD Submicron Emulsion places the stability of 1,2,3,4,5 months respectively
Table 41 month shelf-stability of PPD Submicron Emulsion
Table 52 months shelf-stabilities of PPD Submicron Emulsion
Table 63 months shelf-stabilities of PPD Submicron Emulsion
Table 74 months shelf-stabilities of PPD Submicron Emulsion
PPD Submicron Emulsion preparation prepared by the present invention, respectively at 4,20,30 DEG C of stability tests 4 months, has good stability.
The impact on chemotherapy mouse hematopoetic cell of the Submicron Emulsion preparation
1, the external dosing of protopanoxadiol emulsion for injection is to bone marrow suppression bone marrow cells in mice grain system (CFU-GM), red system
(CFU-E/BFU-E) impact that hematopoietic progenitor population generates.
After experiment uses endoxan 200mg/kg, modeling of lumbar injection, modeling three days, extracting marrow cell collects
Fall to cultivating, in cultivating system, add the medicine of variable concentrations simultaneously.The results are shown in Table 8.
Protopanoxadiol emulsion for injection can be obviously promoted three kinds of HPCs increasings in vitro as can be seen from the results
Growing, colony productivity is obviously higher than model group (P < 0.05 or 0.01).
The impact on bone marrow suppression mouse hemopoietic progenitor population number of the table 8 protopanoxadiol emulsion for injection
Compare with model comparison*P < 0.05,**P < 0.01,***P<0.001
2, in protopanoxadiol emulsion for injection body, dosing is thin to bone marrow suppression bone marrow cells in mice grain system, erythroid hematopoiesis ancestral
The impact of born of the same parents' colony formation.
Experimental day intraperitoneal injection of cyclophosphamide (CP) modeling, after modeling, the intravenous injection immediately of administration group gives protoplast and joins two
Alcohol emulsion for injection medicine, Normal group and model group give the distilled water of same volume, be administered volume and be 0.2ml/10g,
Successive administration 7 days, 7d often group takes 3 and carries out HPC cultivation the most upon administration, within the 1st, 3,5,7 day after modeling, takes
Blood surveys routine blood test.
1. Colony cultivation result: result can be seen that the protopanoxadiol emulsion for injection of various dose is little from following table
Three kinds of proliferation of hematopoietic progenitors can be obviously promoted in mouse body；
The impact on three kinds of proliferation of hematopoietic progenitors of mouse of the table 9 protopanoxadiol emulsion for injection
* P < 0.05, * * P < 0.01, * * * P < 0.001 is compared with model comparison
2. routine blood test result: from following table, the 7th day 75 and 150mg/kg dosage group murine interleukins after administration
(WBC) raise clearly.
Table 10 routine blood test measurement result
| Basis | 3rd day | 5th day | 7th day | |
| Normal group | 4.43±1.75 | 6.92±0.59 | 7.10±0.76 | 8.05±1.44 |
| Model group | 4.43±1.73 | 2.17±0.33 | 1.90±0.37 | 5.17±0.37 |
| 75mg/kg group | 4.57±2.19 | 1.87±0.47 | 1.89±0.81 | 19.24±5.16* |
| 150mg/kg group | 4.60±2.30 | 2.17±0.34 | 1.71±0.37 | 21.86±2.25*** |
* P < 0.05, * * P < 0.01, * * * P < 0.001 is compared with model comparison.
Claims (10)
1. a protopanoxadiol Submicron Emulsion preparation, it is characterised in that described Submicron Emulsion preparation includes protopanoxadiol, oil, breast
Agent, assistant for emulsifying agent, its average grain diameter is 110～130nm, and Zeta potential is-20～-40mV.
2. preparation as claimed in claim 1, it is characterised in that in described Submicron Emulsion preparation, each component content is: protoplast joins two
Alcohol 0.1-0.5%, oil 10-30%, emulsifying agent and assistant for emulsifying agent 3-4%.
3. preparation as claimed in claim 2, it is characterised in that described oil content is 10～15%, emulsifying agent and assistant for emulsifying agent
Ratio be 2:1～2.
4. preparation as claimed in claim 1, it is characterised in that described grease separation is from vegetable oil, animal oil, mineral oil or synthesis
Oil；Described emulsifying agent is in Fabaceous Lecithin, yolk phospholipid, phosphatidyl-ethanolamine, serinephosphatide, lipositol, phosphatidic acid
Any one or a few；Described assistant for emulsifying agent is selected from poloxamer or solutol.
5. preparation as claimed in claim 1, it is characterised in that described vegetable oil is soybean oil or peanut oil；Described emulsifying agent
For Fabaceous Lecithin or yolk phospholipid.
6. the preparation method of protopanoxadiol Submicron Emulsion preparation as described in any one of claim 1-5, it is characterised in that described side
Method comprises the steps:
Step 1, the preparation of oil phase: add emulsifying agent and effective dose protopanoxadiol in appropriate oil, dispersion obtains oil phase；
Step 2, the preparation of aqueous phase: qs glycerin, assistant for emulsifying agent are dissolved in suitable quantity of water, make aqueous phase；
Step 3, just emulsification: under the conditions of 60～70 DEG C, oil phase is added aqueous phase, make colostrum；
Step 4, homogeneous: taking the primary emulsion of step 3 preparation, homogeneous, emulsification, is 110～130nm to emulsion droplet average grain diameter；
Step 5, filling, sterilizing.
7. method as claimed in claim 6, it is characterised in that step 3 carries out ultrasonically treated after oil phase adds aqueous phase, ultrasonic
Time is 5-60min；Step 4 homogenization pressure is 500-2000bar, and cycle-index is 5-20 time.
8. method as claimed in claim 7, it is characterised in that ultrasonic time is 10-20min；Homogenization pressure is 1000-
2000bar, cycle-index is 5-15 time；Preferably, ultrasonic time is 10min；Homogenization pressure is 2000bar, cycle of higher pressure time
Number is 10 times.
9. the protopanoxadiol Submicron Emulsion preparation that as claimed in claim 6 prepared by method promotes hematopoietic cell proliferation or slow in preparation
Solve the application in the medicine of the bone marrow inhibition that oncotherapy produces；Preferably facilitate bone marrow cell grain system and/or erythroid hematopoiesis
Progenitor population generates.
10. protopanoxadiol promotes hematopoietic cell proliferation in preparation or alleviates the medicine of the bone marrow inhibition that oncotherapy produces
In application；Preferably facilitate bone marrow cell grain system and/or hemopoietic progenitor cell of red blood cell line colony formation.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110623926A (en) * | 2019-10-31 | 2019-12-31 | 沈阳药科大学 | A kind of panaxatriol supersaturated self-microemulsion and its preparation method |
| CN112263585A (en) * | 2020-11-04 | 2021-01-26 | 复旦大学附属妇产科医院 | Application of protopanaxadiol PPD in the preparation of medicines for infertility and abortion |
| CN114425038A (en) * | 2022-01-27 | 2022-05-03 | 沈阳信康药物研究有限公司 | 20(S) -PPD liposome emulsion complex oral administration preparation and preparation method and application thereof |
| CN114831935A (en) * | 2022-05-18 | 2022-08-02 | 沈阳信康药物研究有限公司 | Sterile 20(S) -PPD oral liquid preparation capable of being administrated by nasal feeding and preparation method and application thereof |
| CN117442522A (en) * | 2023-11-23 | 2024-01-26 | 云南贝泰妮生物科技集团股份有限公司 | A high-content, high-stability ginsengdiol preparation and its preparation method and application |
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2016
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110623926A (en) * | 2019-10-31 | 2019-12-31 | 沈阳药科大学 | A kind of panaxatriol supersaturated self-microemulsion and its preparation method |
| CN110623926B (en) * | 2019-10-31 | 2022-05-20 | 沈阳药科大学 | A kind of panaxatriol supersaturated self-microemulsion and preparation method thereof |
| CN112263585A (en) * | 2020-11-04 | 2021-01-26 | 复旦大学附属妇产科医院 | Application of protopanaxadiol PPD in the preparation of medicines for infertility and abortion |
| CN114425038A (en) * | 2022-01-27 | 2022-05-03 | 沈阳信康药物研究有限公司 | 20(S) -PPD liposome emulsion complex oral administration preparation and preparation method and application thereof |
| CN114425038B (en) * | 2022-01-27 | 2023-03-10 | 沈阳信康药物研究有限公司 | 20 (S) -PPD liposome emulsion complex oral administration preparation and preparation method and application thereof |
| CN114831935A (en) * | 2022-05-18 | 2022-08-02 | 沈阳信康药物研究有限公司 | Sterile 20(S) -PPD oral liquid preparation capable of being administrated by nasal feeding and preparation method and application thereof |
| CN114831935B (en) * | 2022-05-18 | 2023-04-07 | 沈阳信康药物研究有限公司 | Sterile 20 (S) -PPD oral liquid preparation capable of being administrated by nasal feeding and preparation method and application thereof |
| CN117442522A (en) * | 2023-11-23 | 2024-01-26 | 云南贝泰妮生物科技集团股份有限公司 | A high-content, high-stability ginsengdiol preparation and its preparation method and application |
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