CN108524488A - A kind of pharmaceutical composition containing effective component in red sage and its granule preparation method and application - Google Patents
A kind of pharmaceutical composition containing effective component in red sage and its granule preparation method and application Download PDFInfo
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Abstract
The present invention provides a kind of pharmaceutical composition containing effective component in red sage and its granule preparation method and application, belong to drug field.The pharmaceutical composition includes tanshin polyphenolic acid B, tanshinone IIA, succinic acid and Rosmarinic acid etc..Preparation method, including：Salvia piece is extracted, filtering, concentrates, is dry to get the composition, and the composition is mixed with auxiliary material, pelletized, whole grain, always mixes, packs to get granule.The stability of the granule is good, and quality controllability is strong, can be used for strengthen immunity and treatment diabetes.
Description
Technical field
The present invention relates to drug field, in particular to a kind of pharmaceutical composition containing effective component in red sage and its
Granule preparation method and application.
Background technology
Granule marketing scale is small, production capacity amplification is set about by great market potential, main manufacturing enterprise, in the coming years
Medicine composition particle will keep 30% or so speedup, until 2018 by rapid growth to 18,800,000,000 yuan.But current granule life
Production method falls behind, and people are look for a kind of efficient granule production method.
Immunity is the defense mechanism of human body itself, be human bioequivalence and eliminate any foreign matter of external intrusion (virus,
Bacterium etc.), handle the own cells of aging, damage, death, denaturation, and identification and processing vivo mutations cell and virus sense
The ability for contaminating cell is human bioequivalence and excludes the physiological reaction of " dissident ".
" immune " word, sees ming dynasty of china medical book earliest《Immune class side》, refer to " exempting plague ", that is, anti-
Control the meaning of infectious disease." immune " word also has the ability meaning of body from viral, severe external environment, also can refer to spirit
On resistance.
Immunity refers to that body resists external invasion, safeguards the ability of homoiostasis.It is filled in air various
The microorganism of various kinds：Bacterium, virus, mycoplasma, Chlamydia, fungi etc..It is hypodynamic in human immunity, they
The pathogen of class as early as possible can be become.Although human body will produce corresponding antibody to different pathogen, felt again with resisting
Dye, but antibody has specificity and time-bounded, for example, hammer bacteria antibody can only protect body not by hammer in short period of time
The infringement again of bacterium can not also resist the infection of other viruses.
Modern medical science finds that it is a factor for having substantial connection with aging to be immunized, and immunocyte decline is aging
One of most important reason.Some special cells of body immune system can by invasion body bacterium, virus and declined in vivo
Old dead cell, the cell being mutated and the substance for causing allergy, are wholly swallowed and are eliminated, from internal
The stabilization of environment keeps body health.But body's immunity began to decline at 30 years old or so, and this variation is quietly, delays
Slowly it, is continued for.
A variety of causes prevents immune system from normally playing protective effect, in the case, easily incur bacterium, virus,
The infection such as fungi, therefore it is exactly liable to illness that hypoimmunity, which most directly shows,.Because of frequent illness, disappearing for body has been aggravated
Consumption, thus generally have a delicate constitution, the reduction of malnutritive, apathetic, fatigue and weak, appetite, the performances such as sleep disturbance, give birth to
Disease, having an injection to take medicine has become homely food.It is sick every time to be lot more time to restore, and usually recurrent exerbation.It is long
This can cause body and intellectual development bad in the past, also easily induce major disease.When immune function of human body imbalance, or it is immunized
When system is unsound, following point will recurrent exerbation：Flu recurrent exerbation, tonsillitis recurrent exerbation, asthma are sent out repeatedly
Work, bronchitis recurrent exerbation, pneumonia recurrent exerbation, diarrhea recurrent exerbation.
Diabetes (Diabetes mellit μ s, DM) are the metabolic diseases characterized by insulin relative or absolute deficiency
Disease, insulin relative or absolute deficiency causes hyperglycemia, and then leads to three major nutrient metabolic disorder, finally influences patient
Normal physiological function and cause complication.Currently, diabetes have become the third-largest disease for seriously endangering human health.
It is one of the problem of whole world is paid special attention to, global diabetic is growing day by day, it is contemplated that the year two thousand thirty is up to 4.39 hundred million.
Diabetes are various to body harm, but mainly endanger the heart, brain, kidney, blood vessel, nerve, skin etc..According to
National survey reports, the complication of China diabetes patient in the world spot earliest, at most and most serious, as diabetes have
The patient of the course of disease 10 years or more, the complication that 78% or more people has degree different.
In consideration of it, the present invention provides a kind of pharmaceutical composition and its formula for strengthen immunity and treatment diabetes
Particle.
Invention content
The purpose of the present invention is to provide a kind of pharmaceutical compositions containing effective component in red sage and its granule to prepare
Method and purposes, this pharmaceutical composition include a variety of active ingredients, and the stabilization of the granule by the pharmaceutical composition
Property is good, and quality controllability is strong.
In order to realize that the above-mentioned purpose of the present invention, spy use following technical scheme：
In a first aspect, the present invention provides a kind of pharmaceutical composition containing effective component in red sage, pharmaceutical composition includes pellet
Phenolic acid B, tanshinone IIA and succinic acid.
Further, it in preferred embodiments of the present invention, counts in parts by weight, tanshin polyphenolic acid B is 150~600 parts, red
Ginseng II A of ketone is 3~30 parts and succinic acid is 5~35 parts.
Further, it in preferred embodiments of the present invention, counts in parts by weight, tanshin polyphenolic acid B is 200~500 parts, red
Ginseng II A of ketone is 6~20 parts and succinic acid is 10~25 parts.
Further, it in preferred embodiments of the present invention, counts in parts by weight, pharmaceutical composition further includes：Rosemary
Acid.
Further, it in preferred embodiments of the present invention, counts in parts by weight, Rosmarinic acid is 10~50 parts.
Further, in the present invention in strengthen immunity preferred embodiment, counting in parts by weight, tanshin polyphenolic acid B is
600 parts, tanshinone IIA be 6 parts, succinic acid is 35 parts, Rosmarinic acid is 50 parts；In the present invention for hypoglycemic preferable reality
It applies in example, counts in parts by weight, tanshin polyphenolic acid B is 200 parts, tanshinone IIA is 30 parts, succinic acid is 10 parts, Rosmarinic acid 15
Part.
Second aspect, the present invention provide the preparation method of the granule of three kinds of aforementioned pharmaceutical compositions comprising：
Method one takes the net medicine materical crude slice of Radix Salviae Miltiorrhizae, puts into multi-function extractor, extracts 1~2 time, is heated to boiling, and flows back
Extraction 1~2 hour, it is 1.10~1.30 (60 DEG C) that relative density is concentrated into after extracting solution centrifugation, and spray drying or decompression are true
Sky is dry, obtains composition, adds maltodextrin or appropriate dextrin, granule is made.
Method two takes the net medicine materical crude slice of Radix Salviae Miltiorrhizae, is put into extraction tank, and 40~60 DEG C of water that 5~10 times of weight is added impregnate, leaching
It is 1~2 hour to steep the time；Under 90 DEG C~97 DEG C normal pressures dynamic circulation extraction, extraction time 2 are carried out with dynamic circulation equipment
~4 hours, filtration, filtrate concentration was dry, obtains composition, and composition crushes, and adds auxiliary material dextrin or lactose or maltodextrin
Or their compositions, it mixes, Danshen formula particles are made in granulation.
Method three takes the net medicine materical crude slice of Radix Salviae Miltiorrhizae, is put into continuous flow upstream ultrasonic extractor, and 6~10 times of 30~70% second of amount are added
Ultrasound adverse current is extracted after alcohol solution, the ultrasound adverse current extraction 30 every time under room temperature for being 40~80KHz in ultrasonic power
~60min.Extracting solution is filtered, filtrate and filter residue are collected, filter residue repeats ultrasonic adverse current extraction 2~3 times, and every time after extraction
It refilters, merging filtrate, concentrates, recycle ethyl alcohol, until the clear cream that relative density is 1.05~1.25 at 60 DEG C, dry, obtain group
Object is closed, composition crushes, and adds maltodextrin or dextrin in right amount to get Danshen formula particles.
The third aspect, the present invention also provides a kind of aforementioned pharmaceutical compositions to prepare strengthen immunity or reduce diabetes
Purposes in the drug of the death rate.
This pharmaceutical composition containing effective component in red sage provided by the invention, including active component tanshin polyphenolic acid B, pellet
Join II A of ketone, succinic acid and Rosmarinic acid.
Wherein, tanshin polyphenolic acid B has very strong antioxidation, the protective effect to heart, cerebral ischemia, to memory
Dysfunction improves significantly, and has and mitigates extent of liver fibrosis, anti-aging, antitumor action.This product, which has, lives
The effect of blood stagnation resolvation, clearing and activating the channels and collaterals, cures mainly the ishemic stroke caused by stagnation of blood stasis channels and collaterals symptoms include half body extremity numbness, weak
It is powerless, contraction pain, or move unsuccessful, facial paralysis etc..
Tanshinone IIA mainly has following 10 aspect pharmacological actions：(1) coronary artery is acted on：Coronary heart disease is treated,
Coronary artery circulation can be improved, inhibit thrombus disease.(2) myocardial repair is acted on：Danshensu and the equal energy of tanshinone IIA
Significantly extend mouse hypoxia endurance time, mitigates myocardial damage caused by anoxic, meanwhile, improve myocardial contractive power, promotes cardiac muscle again
It is raw.(3) to microcirculation：Salvia heart-soothing capsules can expand animal arteriole, so that capillary network is opened quantity and increase, accelerate
Velocity of blood flow, flow, so as to improve microcirculation disorder.(4) hemorheological property is acted on：Danshensu and tanshinone IIA have inhibition
ADP induced platelet aggregations, the synthesis for inhibiting platelet T XA2 and release vaso-excitor material and promotion fibrin degradation are made
With.The blood and plasma viscosity of coronary heart disease, cerebral ischemia apoplexy and infraction can be reduced, packed cell volume is reduced, passes through
The effect of anti-freezing viscosity reduction makes hemorheology in patients index restore normal.(5) to the effect of blood fat：Danshensu can inhibit endogenous
Property cholesterol synthesis, reduce OxLDL ELISA (LDL) generation, reduce neutral fat, can be used for hyperlipidemia and draw
The atherosclerosis risen.(6) tanshinone IIA confrontation AS formation effect.Ox blood endothelial cell is caused to low-density finger protein
Damage has protective effect.Blood Cholesterol concentration increases, and especially low-density finger protein (LDL) content cholesterol concentration increases
Height can cause arterial endothelial cell to damage, and lead to the generation of atherosclerosis.This research purpose is evaluation tanshinone IIA pair
The influence that EC caused by LDL is damaged.Tanshinone IIA has antioxidation, can prevent the oxidation of LDL, to protect EC, dimension
It holds it and secretes the normal function of PGL2, anti-AS is formed.(7) anti-infective, for suppurative and surgical infection (acute tonsillitis,
Otitis externa, osteomyelitis, postoperative infection etc.).This product is one of Radix Salviae Miltiorrhizae antibiotic effective ingredient, through body outer suppressioning test, to people
Type tubercle bacillus H37Rv bacterium have stronger activity.(8) it is used to treat cervical erosion.(9) certain skin diseases and acne are treated.
(10) hepatitis and leprosy are treated.
Succinic acid mainly has following 5 aspect pharmacological actions：(1) antibacterial action.Succinic acid is in 2mg/ml concentration pair
Staphylococcus aureus, micrococcus catarrhalis and typhoid fever, green pus, deformation, shigella dysenteriae have inhibiting effect.(2) CNS inhibition is made
With.Rat, mouse, cavy, rabbit, cat and dog intraperitoneal injection succinic acid can protect animal confrontation hyperbaric oxygen, electroconvulsive shock and listen source property
It faints from fear.Anticonvulsant action is related with intracerebral GABA content is improved.Hot plate method has analgesic activity, and work is cooperateed with amobarbital
With the also calm and hypothermic effect of drop.(3) anti-ulcer effect.Rat pylorus ligation generate gastric ulcer, intraperitoneal injection or
Oral 50mg/kg is in anti-ulcer effect due to inhibiting gastric secretion and expansion stomach flesh.(4) to the influence of immune function.Fourth
Diacid is dissolved in physiological saline, and NaHCO is added3Adjust pH to 6.4, a concentration of 11.8%, rat is injected intraperitoneally daily with rabbit
1mM (118mg)/kg, 2.5mM (295mg)/kg, 5mM (590mg)/kg even note 7d, one time a day, the 4th day rat after medication
Leukocyte count increases (P<0.025), but phagocytic rate improves unobvious.Rabbit leukocyte count is also obviously increased when dosage is larger,
Phagocytic rate also improves (P simultaneously<0.01).It is injected intraperitoneally in succinic acid 5mg/kg, 48h and connects in specific skin reaction experiment
With 4 times, or injection 1 time daily, it is used in conjunction two weeks, passive and active cutaneous anaphylaxis can be inhibited to the visible succinic acid of rabbit,
And animal blood serum 1gE antibody can be reduced and formed.(5) detoxication.Succinic acid has apparent protection to the mouse in malicious cobra
Effect.
Rosmarinic acid is a kind of natural, has stronger antioxidant activity, helps to prevent free radical from causing
Cell damage, therefore reduce the risk of cancer and artery sclerosis.Rosmarinic acid has stronger anti-inflammatory activity, is confused simultaneously
Repeatedly fragrant acid also has antibacterial, the activity of antiviral and antitumor.Currently, Rosmarinic acid is in the fields such as pharmacy, food, cosmetics
Its important application value is embodied.
Compared with prior art, beneficial effects of the present invention include：
The granule prepared by pharmaceutical composition of the present invention can increase mouse lymphocyte conversion capability, can increase
Add mouse antibodies cellulation number, all has the function of enhancing mouse humoral immune, can have to NK cells in mice activity obviously
Raising acts on, and can be substantially reduced the death rate of diabetes, but the advantageous effect of the granule prepared by different extraction processes
There is different.The pharmaceutical composition system wherein obtained by dynamic circulating water extraction and continuous flow upstream ultrasound ethanol extraction process
Standby granule, more traditional extraction process by water has a clear superiority in terms of the death rate for reducing diabetes, and by dynamic circulating water
Granule prepared by the pharmaceutical composition that extraction process obtains, more traditional water carries and continuous flow upstream in terms of strengthen immunity
Ultrasonic ethanol extraction process has a clear superiority.
Specific implementation mode
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
It will be appreciated that the following example is merely to illustrate the present invention, and it is not construed as limiting the scope of the invention.It is not specified in embodiment
Actual conditions person carries out according to conventional conditions or manufacturer's recommended conditions.Agents useful for same or instrument are can be by commercially available
Buy the conventional products obtained.
In the present invention, aforementioned pharmaceutical compositions can be used alone, and may be made as preparation or to be formulated at least one other
The form of the combination of particle or drug uses.By being applied in combination with said medicine, it can further enhance the present invention's
Strengthen immunity or the effect for reducing distribution of diabetes.
In order to make the pharmaceutical composition or the granule discharge active component rapidly, continuously and in a very long time,
The pharmaceutical composition of the present invention can be manufactured according to those conventional methods in the art are disclosed in.The pharmaceutical composition
Can be able to be particle, powder, tablet, emulsion, syrup, soft capsule, hard capsule with preparation made of pharmaceutically acceptable auxiliary material
With sterilized powder etc..
Herein, it is that can physiologically connect that term " pharmaceutically acceptable ", which refers to the compound when compound is to human administration,
It receives, and the allergic reactions such as gastrointestinal disturbance, dizziness or these similar anaphylactoid systemic anaphylaxis will not occur.
In the present invention, " pharmaceutically acceptable auxiliary material " includes but not limited to：Adhesive (such as microcrystalline cellulose, alginic acid
Salt, gelatin and polyvinylpyrrolidone), filler (such as starch, sucrose, glucose and anhydrous lactic acid), disintegrant (as be crosslinked
PVP, crosslinked carboxymethyl fecula sodium, croscarmellose sodium and low-substituted hydroxypropyl cellulose), lubricant (stearic acid
Magnesium, aluminum stearate, talcum, polyethylene glycol, sodium benzoate), wetting agent (such as glycerine), surfactant (such as hexadecanol) with
And sorbefacient, corrigent, sweetener, diluent, coating agent etc..
The feature and performance of the present invention are described in further detail with reference to embodiments：
Embodiment 1
The net medicine materical crude slice of 299kg Radix Salviae Miltiorrhizaes is taken, is put into multi-function extractor, adds 8 times of amount water, is heated to boiling, refluxing extraction
2 hours, it was 1.10 (60 DEG C) that relative density is concentrated into after extracting solution centrifugation, is spray-dried to get pharmaceutical composition.Medicine group
Closing object adds maltodextrin appropriate, and 120kg Danshen formula particles are made.
The granule is per g 31.2mg containing tanshin polyphenolic acid B, tanshinone IIA 0.39mg, succinic acid 2.0mg, Rosmarinic acid
2.9mg。
Embodiment 2
The net medicine materical crude slice of 299kg Radix Salviae Miltiorrhizaes is taken, is put into extraction tank, 40 DEG C of water that 10 times of weight is added impregnate, soaking time 1
Hour；Under 90 DEG C of normal pressures dynamic circulation extraction, 2 hours extraction times, filtration, filtrate concentration are carried out with dynamic circulation equipment
It is 1.30 (60 DEG C) to relative density, reduced vacuum drying obtains composition, and composition crushes, and adds auxiliary material 1：1：1 dextrin,
The composition of lactose, maltodextrin mixes, and 120kg Danshen formula particles are made in granulation.
The granule is per g 46.9mg containing tanshin polyphenolic acid B, tanshinone IIA 0.24mg, succinic acid 2.6mg, Rosmarinic acid
3.9mg。
Embodiment 3
The net medicine materical crude slice of 897g Radix Salviae Miltiorrhizaes is taken, is put into continuous flow upstream ultrasonic extractor, after 10 times of 30% ethanol waters of amount are added
Ultrasonic adverse current is extracted, the ultrasound adverse current extraction 30min each under room temperature for being 80KHz in ultrasonic power.Filtering extraction
Liquid collects filtrate and filter residue, and filter residue repeats ultrasonic adverse current extraction 3 times, and is refiltered after extraction every time, and merging filtrate is dense
Ethyl alcohol is recycled in contracting, until the clear cream that relative density is 1.25 at 60 DEG C, reduced vacuum drying obtain composition, composition crushes,
Add maltodextrin in right amount to get 360g Danshen formula particles.
The granule is per g 12mg containing tanshin polyphenolic acid B, tanshinone IIA 2.2mg, succinic acid 0.41mg, Rosmarinic acid
0.81mg。
Embodiment 4
The net medicine materical crude slice of 299kg Radix Salviae Miltiorrhizaes is taken, is put into multi-function extractor, twice, for the first time plus 8 times are measured water, heating for extraction
To boiling, refluxing extraction 2 hours, extracting solution centrifugation is extracted for the second time, is added 6 times of amount water, is heated to boiling, refluxing extraction 1 is small
When, it is 1.30 (60 DEG C) that relative density is concentrated into after extracting solution centrifugation, and reduced vacuum drying obtains composition, composition powder
It is broken, add dextrin appropriate, 120kg Danshen formula particles are made.
The granule is per g 30.3mg containing tanshin polyphenolic acid B, tanshinone IIA 0.56mg, succinic acid 2.52mg, Rosmarinic acid
3.02mg。
Embodiment 5
The net medicine materical crude slice of 299kg Radix Salviae Miltiorrhizaes is taken, is put into extraction tank, 60 DEG C of water that 5 times of weight is added impregnate, and soaking time is 2 small
When；Dynamic circulation extraction is carried out with dynamic circulation equipment under 97 DEG C of normal pressures, 4 hours extraction times, is filtered, filtrate is concentrated into
Relative density is 1.10 (60 DEG C), and spray drying obtains composition, and composition adds auxiliary material dextrin, mixes, and pelletizes, and is made
120kg Danshen formula particles.
The granule is per g 50.2mg containing tanshin polyphenolic acid B, tanshinone IIA 0.51mg, succinic acid 2.81mg, Rosmarinic acid
3.96mg。
Embodiment 6
The net medicine materical crude slice of 897g Radix Salviae Miltiorrhizaes is taken, the net medicine materical crude slice of Radix Salviae Miltiorrhizae is taken, is put into continuous flow upstream ultrasonic extractor, 6 times of amounts 70% are added
Ultrasound adverse current is extracted after ethanol water, and the ultrasound adverse current each under room temperature for being 40KHz in ultrasonic power is extracted
60min.Extracting solution is filtered, filtrate and filter residue are collected, filter residue repeats ultrasonic adverse current extraction 2 times, and is refiltered after extraction every time,
Ethyl alcohol is recycled in merging filtrate, concentration, until the clear cream that relative density is 1.05 at 60 DEG C, spray drying, obtain composition, combines
Object adds dextrin in right amount to get 360g Danshen formula particles.
The granule is per g 16.1mg containing tanshin polyphenolic acid B, tanshinone IIA 2.39mg, succinic acid 0.82mg, Rosmarinic acid
1.2mg。
Experimental example 1
The average mice body weight that experimental example uses is 20g, need to take the granule that Examples 1 to 6 is prepared every time
The amount of 6mg daily intakes 2 times, 30 days totally.
1, experimental animal：SPF grades of Kunming kind female mices, weight 18g~22g.
2, experiment packet：Mouse lymphocyte transformation experiment, antibody-producting cell detection, the NK cells of ConA inductions are lived
The measurement of property respectively takes 70 mouse, is divided into 7 groups, every group 10.Control group takes in the dextrin with granule equivalent：It is real
Apply the granule that 1~6 group of correspondence intake Examples 1 to 6 of example is prepared.
3, the mouse lymphocyte transformation experiment (mtt assay) of ConA inductions
It is sterile to take spleen, it is placed in the small plate for filling appropriate sterile Hank liquid, cell suspension is made, through 200 mesh screen mistakes
Filter.It is washed 2 times with Hank liquid, centrifuges 10 minutes (1000r/min) every time.Then cell is suspended in 1mL complete culture solutions,
Living cell counting number is 3 × 10 with RPMI1640 culture solutions adjustment cell concentration6A/mL.Cell suspension point holes is added again
Enter in 24 well culture plates, often hole 1mL, a hole adds 75 μ L of ConA liquid (being equivalent to 7.5 μ g/mL), another hole conduct pair wherein
According to setting 5% carbon dioxide, 37 DEG C of culture 72h.Culture terminates preceding 4h, and supernatant 0.7mL is gently sucked per hole, and 0.7mL is added
RPMI1640 culture solutions without calf serum, while 50 holes μ L/ MTT (5mg/mL) are added, continue to cultivate 4h.Culture terminates
Afterwards, 1mL acid isopropyl alcohol is added per hole, blows and beats mixing, purple crystal is made to be completely dissolved.Then it is dispensed into 96 well culture plates,
3 parallel holes are made in each hole, with microplate reader, survey the OD value at 570nm wavelength.The proliferative capacity of lymphocyte, which is used, to be added
The OD value in the holes ConA subtracts the OD value expression for being not added with the holes ConA.Four groups of mouse lymphocyte conversion capabilities of tablet pair
Influence it is as shown in table 1.
Table 1
By table 1 as it can be seen that Examples 1 to 6 group can increase mouse lymphocyte conversion capability, difference compared with the control group
Significant, there is also differents between group.
4, antibody-producting cell detection (Jerne improves slide methods)
It takes sheep blood brine 3 times, (2000r/min) 10min is centrifuged every time, by hematocrit sheep red blood cell (SRBC)
SRBC is made into the cell suspension of 2% (v/v) with physiological saline, and 0.2mL is injected intraperitoneally per mouse, and 5 days after being immunized, mouse is put to death,
Spleen is taken, is gently ground, cell suspension, the filtering of 200 mesh screens is made with Hank liquid, washing, centrifugation 2 times finally suspend cell
In 8mLHank liquid.Cell is counted, and cell concentration is adjusted to 5 × 106A/mL.After surface layer culture medium is dissolved by heating
It is mixed with the Hank liquid of 7.4,2 times of concentration of equivalent pH value, dispenses small test tube, often pipe 0.5mL, then be added into pipe and matched with SA liquid
50 μ L (v/v) of 10%SRBC, the 20 μ L splenocyte suspensions (5 × 10 of system6A/mL), brush thin layer is poured into after rapid mixing
On the slide of agarose, flat buckle of slide is placed in glass frame after agarose solidification, is put into carbon dioxide incubator and incubates
1.5h, by the diluted complement of SA liquid (1:8) it is added in slide groove after continuing to incubate 1.5h, counts hemolysis plaque number.Tablet
Influence to four groups of mouse antibodies cellulation numbers is as shown in table 2.
Table 2
As shown in Table 2, Examples 1 to 6 group can increase mouse antibodies cellulation number, all have enhancing mouse body fluid
Immune function, difference is significant compared with the control group, and there is also differents between group.
5, the measurement (determination of lactate dehydrogenase method) of NK cell activity
Test mice cervical dislocation is put to death, sterile to take spleen, and splenocyte suspension is made, is washed 2 times with Hank liquid, is centrifuged every time
10min (1000r/min), abandons supernatant and bounces cytoplasm, after 0.5mL 20 seconds splitting erythrocytes of aqua sterilisa are added, adds
2 times of Hank liquid of 0.5mL and 8mL Hank liquid under 1000rpm rotating speeds, centrifuges 10min, with 1mL containing 10% calf serum
RPMI1640 complete culture solutions are resuspended, and with platform phenol orchid dyeing counting (viable count should be 95% or more), adjust cell concentration
It is 2 × 107A/mL takes after passage 1 cells of well-grown YAC-for 24 hours, is cultivated completely with RPMI1640 as effector cell
It is 4 × 10 that liquid, which adjusts cell concentration,5A/mL is as target cell；Taking target cell and each 100 μ L of effector cell, (effect, target are than 50:
1) it, is added in 96 well culture plate of Μ types；Target cell Spontaneous release hole adds target cell and each 100 μ L of culture solution, target cell maximum to release
Discharge hole adds target cell and each 100 μ L of 2.5%Triton；Above-mentioned items are all provided with three parallel holes, in 37 DEG C, 5% carbon dioxide
4h is cultivated in incubator, 96 well culture plates are then centrifuged into 5min with the rotating speed of 1500r/min, per 100 μ L of hole Aspirate supernatant
In 96 well culture plate of horizontalization bottom, while 100 holes μ L/ of LDH matrix liquids are added, according to room temperature reaction 3-10min, 30 μ are added per hole
The HCl of L 1mol/L measures optical density (OD) at microplate reader 490nm wavelength.
NK cell activity=[(reacting hole OD values-Spontaneous release hole OD values)/(maximum release aperture OD values-Spontaneous release hole
OD values)] × 100%.
Tablet is active on four groups of NK cells in mice to be influenced as shown in table 3.
Table 3
By table 3 as it can be seen that Examples 1 to 6 group can the effect of being significantly improved to NK cells in mice activity, with control group ratio
Significant compared with difference, there is also differents between group.
In short, Examples 1 to 6 group energy strengthen immunity, but the pharmaceutical composition obtained by dynamic circulation water extraction process
Granule prepared by object, more traditional water is carried in terms of strengthen immunity has obviously with continuous flow upstream ultrasound ethanol extraction process
Advantage.
Experimental example 2
1, the foundation of diabetic rat model
Streptozotocin (STZ) inducing mouse diabetes (DM) model is injected intraperitoneally using low dose of continuous several times.4 weeks
Age male C 57 BL/6 J mouse configures a concentration of 7.5mg/m1 of STZ with 0.1Mp H4.4 citrate buffers, by 50mg/kg
Dosage is injected intraperitoneally, and one time a day, continuous injection 5 times measures blood glucose value in the 3rd, 7,14 day after modeling, continuous with fasting blood-glucose
Twice >=11.1mmol/L is into mould standard.
2, mortality statistics
84 diabetic mices are randomly divided into 7 groups, every group 12, respectively：Control group, Examples 1 to 6 group.
In model success (be subject to blood glucose >=11.1mmol/L), the 2nd week Examples 1 to 6 group mouse takes in reality every time afterwards
The amount for the granule 6mg that example 1~6 is prepared is applied, the dextrin of control group intake and granule equivalent daily intakes 2
It is secondary, up to dead or 5 months stop.
Count the death rate during each group mouse was observed at 5 months.The results are shown in table below.
| Group | 5 months death rates (%) |
| Control group | 83 |
| 1 group of embodiment | 67 |
| 2 groups of embodiment | 50 |
| 3 groups of embodiment | 42 |
| 4 groups of embodiment | 58 |
| 5 groups of embodiment | 50 |
| 6 groups of embodiment | 33 |
As seen from the above table, Examples 1 to 6 group can be substantially reduced the death rate of diabetes, and difference has compared with the control group
Conspicuousness, there is also differents between group.Wherein obtained by dynamic circulating water extraction and continuous flow upstream ultrasound ethanol extraction process
Pharmaceutical composition prepare granule, reduce diabetes the death rate in terms of more traditional extraction process by water have a clear superiority.
Although above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements, belong to claimed model without departing from theon the basis of the spirit of the present invention
It encloses.
Claims (10)
1. a kind of pharmaceutical composition containing effective component in red sage, which is characterized in that described pharmaceutical composition include tanshin polyphenolic acid B,
Tanshinone IIA and succinic acid.
2. pharmaceutical composition according to claim 1, which is characterized in that count in parts by weight, described pharmaceutical composition is also
Including Rosmarinic acid.
3. pharmaceutical composition according to claim 2, which is characterized in that count in parts by weight, the tanshin polyphenolic acid B is 150
~600 parts, the tanshinone IIA is 3~30 parts, and the succinic acid is 5~35 parts and the Rosmarinic acid is 10~50 parts.
4. pharmaceutical composition according to claim 2, which is characterized in that count in parts by weight, the tanshin polyphenolic acid B is 200
~600 parts, the tanshinone IIA is 6~30 parts, and the succinic acid is 10~35 parts and the Rosmarinic acid is 15~50 parts.
5. pharmaceutical composition according to claim 2, which is characterized in that count in parts by weight, the tanshin polyphenolic acid B is 600
Part, tanshinone IIA are 6 parts, succinic acid is 35 parts, Rosmarinic acid is 50 parts.
6. pharmaceutical composition according to claim 2, which is characterized in that count in parts by weight, the tanshin polyphenolic acid B is 200
Part, tanshinone IIA are 30 parts, succinic acid is 10 parts, Rosmarinic acid is 15 parts.
7. a kind of preparation method according to claim 1~6 any one of them pharmaceutical composition, which is characterized in that it includes：
Salvia piece is extracted, filtering, concentrates, is dry to get the composition.
8. a kind of preparation method according to claim 7 any one of them pharmaceutical composition, which is characterized in that it includes：
Method one takes the net medicine materical crude slice of Radix Salviae Miltiorrhizae, puts into multi-function extractor, extracts 1~2 time, is heated to boiling, refluxing extraction 1
~2 hours, it was 1.10~1.30 (60 DEG C) that relative density is concentrated into after extracting solution centrifugation, and spray drying or reduced vacuum are dry
It is dry, composition is obtained, maltodextrin or appropriate dextrin are added, granule is made；
Method two takes the net medicine materical crude slice of Radix Salviae Miltiorrhizae, is put into extraction tank, and 40~60 DEG C of water that 5~10 times of weight is added impregnate, soaking time
It is 1~2 hour；Under 90 DEG C~97 DEG C normal pressures dynamic circulation extraction is carried out with dynamic circulation equipment, 2~4 hours extraction times,
Filtration, filtrate concentration is dry, obtains composition, and composition crushes, and adds auxiliary material dextrin or lactose or maltodextrin or their group
Object is closed, is mixed, Danshen formula particles are made in granulation；
Method three takes the net medicine materical crude slice of Radix Salviae Miltiorrhizae, is put into continuous flow upstream ultrasonic extractor, and 6~10 times of 30~70% ethanol waters of amount are added
After solution ultrasound adverse current extract, ultrasonic power be 40~80KHz under room temperature every time ultrasound adverse current extraction 30~
60min.Filter extracting solution, collect filtrate and filter residue, filter residue repeats ultrasonic adverse current extraction 2~3 times, and every time after extraction after
Ethyl alcohol is recycled in filter, merging filtrate, concentration, until the clear cream that relative density is 1.05~1.25 at 60 DEG C, dry, obtains composition,
Composition crushes, and adds maltodextrin or dextrin in right amount to get Danshen formula particles.
9. a kind of preparation method of the granule of pharmaceutical composition according to claim 7 or 8, which is characterized in that its
Including：The composition is mixed with auxiliary material, is pelletized, whole grain, total mixed, packaging are to get Danshen formula particles.
10. a kind of Radix Salviae Miltiorrhizae formula according to claim 1~6 any one of them pharmaceutical composition or claim 9
Application of the grain in preparing strengthen immunity or diabetes medicament.
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| CN109528824A (en) * | 2018-12-10 | 2019-03-29 | 江西赣隆药业有限公司 | A kind of radix salviae miltiorrhizae granule and preparation method thereof |
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