CN106511360A - Composition containing ginsenoside Rg3 and silymarin and medicine - Google Patents
Composition containing ginsenoside Rg3 and silymarin and medicine Download PDFInfo
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Abstract
The invention discloses a composition containing ginsenoside Rg3 and silymarin and medicine, and mainly relates to the technical field of medicine. The composition comprises, by weight, 3-7 parts of the ginsenoside Rg3 and 3-7 parts of the silymarin. The composition containing the ginsenoside Rg3 and the silymarin and the medicine have the beneficial effects that the ginsenoside Rg3 and the silymarin are combined according to a certain proportion, the excellent synergistic medicine efficacy is achieved, tumor cells are effectively restrained, lymphopoiesis is stimulated, and the composition and the medicine have the medicine efficacy of efficient cancer fighting and immunity boosting, and also have a health-care effect.
Description
Technical field
The present invention relates to pharmaceutical technology field, specifically a kind of compositionss containing ginsenoside Rg3 and silymarin and
Medicine.
Background technology
Annual new about 1,600,000 people of cancer stricken of China, die from about 1,300,000 people of cancer person.The whole world and the pathogenesis of cancer of China
Rate is substantially increasing year by year.And China's cancer patient it is medical when end-stage patients still occupy the majority, with losing the radical cure such as operation
The characteristics of chance, poor therapeutic effect.By the level of present China's cancer mortality, the whole nation just had 2 people to die from cancer per 1 minute
Disease, will have people more than 2800 to be seized life by cancer daily, and will be equivalent within 1 year a city for having a population of one million and destroyed.It can be seen that,
Cancer is commonly encountered diseases, frequently-occurring disease, and the people life and health person of having seriously is threatened, and the impact to the development of the national economy is also huge
's.In the U.S., 83,000,000,000 dollars of annual treatment of cancer expense accounts for the 14% of national medical expense.Almost everyone experiences cancer
The threat of disease.Because the whole world is up to 6,300,000 people because of the number of cancer mortality every year, and China is every year because of the number of cancer mortality
Up to 1,300,000 people, and cancer patient is every year with 3% speed increase, equivalent to just having 1 family to receive in per 200 families
To the threat of cancer.
At present, everybody " talk about cancer complexion changed ", how to prevent and treat cancer is a global difficult problem.Although clinically having
Very big cancer therapy drug, but do not have a kind of medicine prevent completely and cure cancer.Ginsenoside Rg3 is obtained from Radix Ginseng Rubra earliest,
Its content is only 0.003%, and because its content is too low, complex manufacturing causes production cost higher.Ginsenoside Rg3 has
The activity of significant antitumor and raising body immune function, is adapted to early, middle and late phase tumor patient and immunocompromised prophylaxis of tumours
Generation crowd take.Its mechanism of action is formed to suppress intra-tumor new vesselses；Prevent implantation of the cancerous cell in blood vessel wall that come off；
Suppress infiltration of the tumor cell to blood vessel wall basement membrane, have notable anti-infiltration, metastasis effect.Clinical experiment confirm its have compared with
The growth of cancer cells such as good suppression pulmonary carcinoma, hepatocarcinoma, gastric cancer, intestinal cancer, breast carcinoma, hence it is evident that improve clinical symptoms, improve life quality,
Prevention and treatment cancer, the cardiovascular function that improves, anti-platelet aggregation, protection cranial nerve cell, raising immunity of organisms.Directly
Connect to take and there is prophylaxis of cancer and treating cancer, it is adaptable to which anxious, weight, patient with advanced cancer, body constitution are weaker, take
Autoimmune function can be improved, strengthens anti-tumor ability, mitigate toxic and side effects after chemotherapy.Ginsenoside rg3 and other cancer therapy drugs
There is more preferable effect in terms of use in conjunction, its anticancer and raising body immune function.The Shenyi capsule for clinically using is effective
Composition is ginsenoside rg3, is mainly used in the auxiliary treatment for the treatment of cancer and cancer.
Silymarin (English：Silymarin it is) antioxidant, carries from a kind of entitled Silybum marianum Gaertn (Milk Thistle) plant
Refining is formed.Silymarin can stablize liver plasma membrane, maintain the integrity of hepatocyte, make toxin penetrate destruction liver, and energy
Accelerate the DNA (deoxyribonucleic) of synthesis liver cell, the diseases such as liver cirrhosis, fatty liver, cholangitis, psoriasiss can be prevented, together
When have hepatocarcinoma, carcinoma of prostate, breast carcinoma and cervical cancer cell growth and differentiation inhibitory action.It is to be found in the world at present
The most flavonoid of liver disease curative effect.
If can pharmacologically be combined the two, respective effect is given full play to, and excites synergetic immunity, anticancer, guarantor
Strong effect, will obtain more important progress in field of medicaments.
The content of the invention
It is an object of the invention to provide a kind of compositionss containing ginsenoside Rg3 and silymarin, it is by by people
Ginseng saponin Rg3 and silymarin carry out a certain proportion of combination, make the collaboration drug effect that performance is excellent, effectively suppress tumor cell,
Stimulate lymphopoiesis, with efficient anticancer, the drug effect of enhancing immunity and health-care effect.
The present invention for achieving the above object, is achieved through the following technical solutions：
A kind of compositionss containing ginsenoside Rg3 and silymarin, its component count by weight including：Ginsenoside
Rg33～7 part, 3～7 parts of silymarin.
Preferably, its component count by weight including：4～6 parts of ginsenoside Rg3,4～6 parts of silymarin.
Used as a kind of optimal case, its component includes parts by weight identical ginsenoside Rg3 and silymarin.
A kind of preparation method containing ginsenoside Rg3 and the composite injection of silymarin, comprises the following steps：Will
The water of 50～70g arginine and 50～70g is mixed, and adds 100～170g of 100～170g of ginsenoside Rg3 and silymarin,
45～55 DEG C, after stirring and dissolving are heated to, pH value is adjusted to 4.4～4.8, the water of 400～800ml is added, after stirring
Activated carbon is added, the amount that activated carbon is added is 0.05～0.15%g/ml of total material, after stirring 20～30 minutes, coarse filtration takes off
Charcoal, after 0.20～0.25 μm of filter membrane, obtains fine straining liquid；Embedding, 110～125 DEG C of pressure sterilizings 15～20 minutes, obtains final product injection
Finished product.
Preferably, above-mentioned steps are：
The water of 58g arginine and 58g is mixed, ginsenoside Rg3 and each 137g of silymarin is added, is heated to 50 DEG C,
After stirring and dissolving, pH value is adjusted to 4.6 using 9% aqueous hydrochloric acid solution, add the water of 500ml, be stirring evenly and then adding into work
Property charcoal, activated carbon add amount be total material 0.1%g/ml, stirring 25 minutes after, coarse filtration takes off charcoal, after 0.22 μm of filter membrane,
Obtain fine straining liquid；By per bottled amount 2mL embedding, 118 DEG C of pressure sterilizings 18 minutes obtain final product injection finished product.
A kind of composition tablet containing ginsenoside Rg3 and silymarin, its raw materials by weight portion meter include：Radix Ginseng
5～30 parts of saponin Rg3,5～30 parts of silymarin, 40～65 parts of Lactose, 2～3 parts of carboxymethyl starch sodium, micropowder silica gel 4～5
Part, 50～70 parts of arginine, 4～6 parts of carboxymethyl starch sodium, 1～2 part of micropowder silica gel.
Preferably, a kind of raw materials by weight portion containing ginsenoside Rg3 and the composition tablet of silymarin
Meter includes：15 parts of ginsenoside Rg3,15 parts of silymarin, 55 parts of Lactose, 2.6 parts of carboxymethyl starch sodium, micropowder silica gel 4.3
Part, 63 parts of arginine, 5.2 parts of carboxymethyl starch sodium, 1.5 parts of micropowder silica gel.
Contrast prior art, the beneficial effects of the present invention is：
By the compositionss active anticancer and enhancing human body immunity work(of pharmacological experiment, ginsenoside Rg3 and silymarin
Can activity to be superior to ginsenoside Rg3, i.e. compositionss pharmacologically active stronger than the cancer therapy drug of one-component, illustrate that the two combination has
There is a pharmacological action of collaboration, and 1:During 1 weight proportion, synergistic action effect is optimal, acts on excellent pharmacological effect.
This discovery to prevent and treat cancer medicine and health product exploitation in terms of have positive effect.
The present composition tests prove that and can effectively suppress tumor cell, and stimulation lymphopoiesis are low dose of to combine
Thing does not stimulate the ability of lymphocytic emiocytosis IL-2 and IFN-γ, heavy dose of compositionss to have obvious stimulation to stimulate lymphocyte
Secretion IL-2 and IFN-γ.
In practice, the present invention compositionss can make tablet, capsule, decoction, oral liquid, electuary, pill,
The dosage form of injection.The tablet includes sugar coated tablet, film coated tablet, enteric coated tablet, buccal tablet；The capsule bag
Include hard capsule, soft capsule；The electuary includes granule and powder；The injection include freeze-dried powder, vein emulsion,
Injection liquor.Wherein, oral formulations are preferably tablet, capsule, granule；Injection preparation is preferably freeze-dried powder, vein
Emulsion, injection liquor.
Specific embodiment
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than limit the scope of the present invention.In addition, it is to be understood that after the content for having read instruction of the present invention, people in the art
Member can be made various changes or modifications to the present invention, and these equivalent form of values equally fall within the application appended claims and limited
Scope.
Involved instrument, reagent, material etc. in following embodiments, unless otherwise noted, have in being prior art
Conventional instrument, reagent, material etc., can be obtained by regular commercial sources.Involved experimental technique in following embodiments, inspection
Survey method etc., unless otherwise noted, is existing normal experiment method in prior art, detection method etc..
Embodiment 1：A kind of compositionss containing ginsenoside Rg3 and silymarin, its component count by weight including
3.5 parts of ginsenoside Rg3,6.5 parts of silymarin.
Embodiment 2：A kind of compositionss containing ginsenoside Rg3 and silymarin, its component count by weight including
6 parts of ginsenoside Rg3,4 parts of silymarin.
Embodiment 3：A kind of compositionss containing ginsenoside Rg3 and silymarin, its component count by weight including
1 part of ginsenoside Rg3,1 part of silymarin.
Embodiment 4：A kind of composite injection containing ginsenoside Rg3 and silymarin
Its preparation method is：
Weigh arginine 58g, etc. quality water, stir, add ginsenoside Rg3 125g, silymarin 150g,
50 DEG C are heated to, stirring and dissolving adjusts pH value to 4.6 with containing 9% salt aqueous acid, adds water to 500ml amounts, stirs；Again
The activated carbon with liquid measure 0.l% (g/ml) is added, is stirred 25 minutes, coarse filtration takes off charcoal；0.22 μm of filter membrane is crossed, fine straining liquid is obtained；Embedding,
Per bottled amount 2mL；118 DEG C of pressure sterilizings 18 minutes, inspection, packaging, warehouse-in.
Embodiment 5：A kind of composition tablet containing ginsenoside Rg3 and silymarin
Its preparation method is：
1) will stir after ginsenoside Rg3 20g, silymarin 10g mixing, obtain pulverulent solids；
2) powder obtained by step (1) is mixed with Lactose 55g, carboxymethyl starch sodium 2.6g and micropowder silica gel 4.3g
It is even, add arginine 63g to make suitable soft material, the granulation of 20 mesh sieves；
3) carboxymethyl starch sodium 5.2g and micropowder silica gel 1.5g is mixed with the dry particl obtained by step (2), and tabletting obtains piece
Agent.
Embodiment 6：A kind of mouse experiment of the compositionss antitumor application thereof containing ginsenoside Rg3 and silymarin
Cell：
B16 melanoma cell (B16melanoma cell)；
Human liver cancer cell (HepG2) cell is obtained from American Type Cell storehouse (ATCC, Hanassas, VA, USA) purchase.
Culture medium：
Cell culture DMEM liquid culture (FBS；HyClone, Logan, UT, USA), culture fluid adds 10% hyclone
(FBS；HyClone, Logan, UT, USA), 0.03%L glutamine, 100U/L green grass or young crops enzyme elements, 100mg/L streptomycins, 5%
NaCO2 adjusts pH to 6.8 7.0.
Sample：
Experimental group 1：Ginsenoside Rg3 30% and silymarin 70%；
Experimental group 2：Ginsenoside Rg3 50% and silymarin 50%；
Experimental group 3：Ginsenoside Rg3 70% and silymarin 30%.
Compositionss are dissolved with 20 μ l dimethyl sulfoxide (DMSO), for configuring the DMEM cell culture mediums of variable concentrations.It is purple
China fir alcohol (TAX：) and cisplatin (PPD Paclitaxel：Cisplatin) purchased from Sigma Chemical companies (St.Louis, MO).
Equipment：
Microplate reader Bio-RAD 680 (USA)；
CO2 incubator Thermo Forma 3310 (U.S.)；
Inverted biological microscope XD-101 types (Nanjing) etc..
Growth inhibited evaluation to tumor cell：
The normal Kunming hamster kidney cell of original cuiture, B16 cells and HepG2 cells are with cell density as 1 × 104/ml
After cultivating 24 hours in being inoculated in 96 orifice plates, common DMEM culture medium is changed to containing final concentration of 0 μ g, 25 μ g, 50 μ g, 75 μ
The DMEM culture medium of the different group chemical combination of g, 100 μ g, each concentration sets 3 holes, and detects cell with mtt assay at 24 hours later
Activity, cell inhibitory activity are represented with inhibition concentration IC50 (median inhibitory concentration).Inhibition concentration
(IC50) drug level when being 50% for cytoactive inhibiting rate, computational methods are IC50=(ACell controls group- ATest sample group)/
ACell controls group- ABlank group) × 100%.
Mtt assay：According to Mosmann set up mtt assay detection medicine cytotoxicity (Y.Nakajima, Y.Saton,
M.Katsumata,K.Tsujiyama,Y.Ida,and J.Shoji,Phytochemistry 1994,36,119-127).Tool
Body method is：0.4mg/mL MTT, 0.1mL/ holes, 37 DEG C of 5%CO are added in the cell hole for suck supernatant2Culture 4h, goes
Clearly, 0.1mL dimethyl sulfoxide (DMSO) is added per hole, is incubated 10min, extinction of the solution under 570nm is determined in microplate reader
Angle value.
Half-inhibition concentration IC of the table 1 to tumor cell50(μg/mL)
As shown in table 1, positive controls (TAX, PPD) and three experimental grouies are to B16 and HepG2 cells for experimental result
There is inhibitory action.To the half-inhibition concentration IC50 of B16 cells in below 50 μ g/ml.Also, all relevant sets are to normal mouse
The no toxicity of nephrocyte.
Immunoregulatory activity is detected：
125 18～20g kunming mices are randomly divided into according to 5 per group：Physiological saline group, 12 groups 1mg/kg and 12 group
The test group of 4mg/kg, experimental group is：Experimental group 1：Ginsenoside Rg3 30% and silymarin 70%；Experimental group 2：Radix Ginseng soap
Glycosides Rg3 50% and silymarin 50%；Experimental group 3：Ginsenoside Rg3 70% and silymarin 30%.Daily abdominal cavity respectively
The compound group of injecting normal saline or 4mg/kg.Put to death after 7 days, and dislocation takes spleen preparation and tests below.
1) mtt assay determines lymphopoiesis ability
It is aseptic to prepare splenocyte suspension, adjust cell concentration to be 1 × 107/mL.Per 100 μ L of hole.If cell control well (plus
DMEM culture fluid) and Con A Concanavalin (ConA) stimulation hole (concentration of ConA is 5mg/L).In 37 DEG C of CO2Culture 48h, plus
Enter the MTT solution of 5mg/mL, 37 DEG C of 5%CO2Culture 4h, removes supernatant, and 100 μ L dimethyl sulfoxide (DMSO), incubation are added per hole
10min, determines absorbance A of the solution under 570nm in microplate reader.Calculate stimulation index (SI).SI=stimulates hole A average
Value/control wells Aaverage.
Experimental result is shown in Table 2, and positive controls (TAX, PPD) do not stimulate lymphopoietic effect, three realities
Testing group can stimulate lymphopoiesis.
2) NK cells against tumor cells kill toxicity test
By 100 μ L mouse boosting cells (1 × 107/ mL) cell concentration 50 is pressed with 100 μ L YAC-1 cells：1 ratio is added
96 orifice plates.If target cell (YAC-1 cells) control, effector lymphocyte's (each compound group mouse boosting cell) control, each 3 multiple holes.In
37 DEG C, 5%CO2Incubator culture 18h, adds MTT solution, determines A570 values.Calculate NK cell toxicant percentage rate：NK cell toxicant percentages
Rate=[1- (effect wad cutter A values-effect control wells A value)/target control wells A value] × 100%.
Test and the results are shown in Table 2, positive controls (TAX, PPD) do not strengthen the effect of NK cells against tumor cells killing.
NK cells against tumor cells kill toxicity test and show that low dose of experimental group can strengthen the lethal of NK cells, have stronger
Activity.
2 lymphopoiesis ability (SI) of table and NK cells against tumor cells kill the impact (%) of toxicity
(n=5,* represent and stimulation group compares P<0.05)
3) in spleen cell cultures supernatant, IL-2 and IFN-γ secretion are determined
IL-2 determinations of activity adopt mice T lymphoblast method of proliferating, and the surveyed A570 values of mtt assay are in positive with IL-2 activity
Close, IFN-γ determination of activity adopts L929 cytopathic-effect inhibition assay, the surveyed A540 values size reflection IFN-γ of violet staining to live
The height of property.During spleen cell cultures supernatant is added to mice T lymphoblasts or L929 cells, the upgrowth situation of two kinds of cells
Reflect corresponding cytokine content.
Impact of 3 experimental group of table to IL-2 and IFN-γ secretion (n=5,* represent and stimulation group compares P<0.05)
Experimental result is shown in Table 3, and positive controls (TAX, PPD) do not stimulate lymphocytic emiocytosis IL-2 and IFN-γ
Ability.Three experimental group small dose groups do not stimulate the ability of lymphocytic emiocytosis IL-2 and IFN-γ, and heavy dose of group has bright
It is aobvious to stimulate lymphocytic emiocytosis IL-2 and IFN-γ.
Claims (7)
1. a kind of compositionss containing ginsenoside Rg3 and silymarin, it is characterised in that：Its component counts bag by weight
Include：3～7 parts of ginsenoside Rg3,3～7 parts of silymarin.
2. a kind of compositionss containing ginsenoside Rg3 and silymarin according to claim 1, it is characterised in that：Its group
Meter by weight is divided to include：4～6 parts of ginsenoside Rg3,4～6 parts of silymarin.
3. a kind of compositionss containing ginsenoside Rg3 and silymarin according to claim 2, it is characterised in that：Its group
Dividing includes parts by weight identical ginsenoside Rg3 and silymarin.
4. using a kind of composite injection containing ginsenoside Rg3 and silymarin as described in any one of claims 1 to 3
Preparation method, it is characterised in that：Comprise the following steps：
The water of 50～70g arginine and 50～70g is mixed, add 100～170g of ginsenoside Rg3 and silymarin 100～
170g, is heated to 45～55 DEG C, after stirring and dissolving, and pH value is adjusted to 4.4～4.8, adds the water of 400～800ml, and stirring is equal
Activated carbon is added after even, the amount that activated carbon is added is 0.05～0.15%g/ml of total material, after stirring 20～30 minutes, coarse filtration
De- charcoal, after 0.20～0.25 μm of filter membrane, obtains fine straining liquid；Embedding, 110～125 DEG C of pressure sterilizings 15～20 minutes, obtains final product injection
Liquid finished product.
5. a kind of preparation method containing ginsenoside Rg3 and the composite injection of silymarin according to claim 4,
It is characterized in that：Comprise the following steps：
The water of 58g arginine and 58g is mixed, ginsenoside Rg3 and each 137g of silymarin is added, is heated to 50 DEG C, stirred
After dissolving, pH value is adjusted to 4.6 using 9% aqueous hydrochloric acid solution, adds the water of 500ml, be stirring evenly and then adding into activated carbon,
The amount that activated carbon is added is the 0.1%g/ml of total material, and after stirring 25 minutes, coarse filtration takes off charcoal, after 0.22 μm of filter membrane, obtains fine straining
Liquid；By per bottled amount 2mL embedding, 118 DEG C of pressure sterilizings 18 minutes obtain final product injection finished product.
6. using a kind of composition tablet containing ginsenoside Rg3 and silymarin as described in any one of claims 1 to 3,
It is characterized in that：Its raw materials by weight portion meter includes：5～30 parts of ginsenoside Rg3,5～30 parts of silymarin, Lactose 40
～65 parts, it is 2～3 parts of carboxymethyl starch sodium, 4～5 parts of micropowder silica gel, 50～70 parts of arginine, 4～6 parts of carboxymethyl starch sodium, micro-
1～2 part of powder silica gel.
7. a kind of composition tablet containing ginsenoside Rg3 and silymarin according to claim 6, it is characterised in that：
Its raw materials by weight portion meter includes：15 parts of ginsenoside Rg3,15 parts of silymarin, 55 parts of Lactose, carboxymethyl starch sodium 2.6
Part, 4.3 parts of micropowder silica gel, 63 parts of arginine, 5.2 parts of carboxymethyl starch sodium, 1.5 parts of micropowder silica gel.
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| CN108578418A (en) * | 2018-04-16 | 2018-09-28 | 云南中医学院 | A kind of composition of medicine for treating diabetes wound surface in refractory to treatment complication |
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