Background technology:
Operation, chemotherapy and radiotherapy are three great tradition therapies of treatment malignant tumor.Yet relapse rate is but high always behind the malignant tumor operation, and chemotherapy and radiotherapy not only bring the side effect of destruction property to the patient, and often owing to problems such as chemical sproof generation and sensitivity are not strong make curative effect limited.
Radix Salviae Miltiorrhizae is the Chinese medicine of China, has the effect of blood circulation promoting and blood stasis dispelling, dredge the meridian passage.Salvianolic acid B is one of aqueous soluble active constituent of Radix Salviae Miltiorrhizae, and its chemical constitution is as follows:
Wherein, F is a metal cation; discovering these years; water-soluble components is important active ingredient in the Radix Salviae Miltiorrhizae; because salvianolic acid is difficult to obtain pure product; and danshensu and protocatechualdehyde are more easily separated and synthetic; so most of pharmaceutical factories are danshensu and the protocatechualdehyde quality control index as Danshen root injection; also there is part pharmaceutical factory that salvianolic acid B salt is used to prevent cardiovascular and cerebrovascular disease, prevention alzheimer disease; treatment renal failure is improved in the medicines such as uremic symptom, antioxidation, antithrombotic, anti-cardiac-cerebral ischemia, the liver protecting and blood lipid regulation.
Summary of the invention:
Technical problem to be solved by this invention is: because in the prior art; most of pharmaceutical factories are danshensu and the protocatechualdehyde quality control index as Danshen root injection; also have salvianolic acid B salt is used to prevent cardiovascular and cerebrovascular disease, prevention alzheimer disease; treatment renal failure is improved in the medicines such as uremic symptom, antioxidation, antithrombotic, anti-cardiac-cerebral ischemia, the liver protecting and blood lipid regulation.But do not meet the application in the medicine of using it for preparation treatment tumor.The present invention is for solving the above-mentioned technical problem in the prior art, and the technical scheme that is adopted provides the new purposes of salvianolic acid B, i.e. the application of salvianolic acid B in preparation medicine for treating tumor thing.At the salt apoplexy due to endogenous wind of salvianolic acid B of the present invention, its cation can be iron ion, sodium ion, potassium ion, calcium ion or magnesium ion, preferably magnesium ion.The dosage form of the medicine of preparation of the present invention treatment tumor can be oral liquid type, injection type, tablet form or capsule-type for the above dosage form of any pharmaceutics.In vitro study shows that salvianolic acid B has lethal effect to tumor cell, experimental results show that in the animal body that it has antitumor curative effect.
Description of drawings:
Fig. 1 suppresses the dose-effect relationship figure of growth of tumour cell for salvianolic acid B.
Wherein, abscissa is represented the concentration of salvianolic acid B solution, and unit is umol/L; Vertical coordinate is represented
Absorbance (A).1 is the SK-Hep1 cell strain, and 2 is the Huh-7 cell strain, and 3 is SMMU-7721
Cell strain, 4 is the H22 cell strain, 5 is the Hela cell strain.
Fig. 2 is the influence of salvianolic acid B to the transplanted hepatoma mice time-to-live.
Wherein, abscissa express time (natural law), vertical coordinate is represented the number of elements of survival mice,
■ is not administration group, ▲ be the administration group.
Fig. 3 lures the therapeutical effect figure of cancer rat liver cancer for salvianolic acid B to chemistry.
Wherein, ■ is a tumor group, treatment group,
Be normal group.
The specific embodiment:
Embodiment 1
The extracting method of Radix Salviae Miltiorrhizae
Radix Salviae Miltiorrhizae (Salvia miltionrrhiza Bge.) is ground into 100 order powder after removing impurity such as silt, and water heating extraction three times merges aqueous extract, and concentrating under reduced pressure, concentrated solution add alcohol (methanol, ethanol) and contain the alcohol amount to 70-80%, put cold spending the night; Remove precipitation with centrifuge, solution is removed alcohol, crosses macroporous resin (model Diaion HP20 or 400-1 type), water, ethanol elution, collect the phenolic acid part, be concentrated into small size, again by gel column (MCI gel, TSK HF40w, SephadexLH-20, Silica gel ODSG3 etc.), water one ethanol elution is collected the eluent that contains the salvianolic acid B part.With the eluent rotary evaporation in vacuo, remove ethanol, lyophilization obtains salvianolic acid B dry powder.
Embodiment 2
Salvianolic acid B suppresses the dose-effect relationship figure of growth of tumour cell
Select human hepatoma cell strain SK-Hepl, Huh7, SMMU-7721, rat liver cancer cell strain H22, human cervical carcinoma cell strain Hela experimentize (except that the Hela cell strain available from Shanghai RESEARCH ON CELL-BIOLOGY institute of the Chinese Academy of Sciences cell bank, above cell strain is all by the present of auspicious moral hepatic disease institute).Cultivate above-mentioned cell respectively with the RPMI-1640 that contains 10% calf serum (available from Sigma) culture fluid,, prepare cell suspension, and cell concentration is transferred to 1 * 10 with 0.25% pancreatin (available from Sigma) digestion cell monolayer
5/ ml.Get 96 well culture plates, every hole adds 100ul cell suspension, and overnight incubation makes cell attachment.0.27,2.7,27,270umol/L culture fluid is removed in suction, adds the culture fluid contain salvianolic acid B, and the salvianolic acid B final concentration is respectively:, observe its effect to tumor cell with tetrazolium (MTT) (available from Sigma) reducing process after 48 hours.Fig. 1 shows that the salvianolic acid B of each concentration all has inhibitory action to tumor cell, and has dose-effect relationship.
Embodiment 3
Salvianolic acid B is to the effect of animal inoculation tumor treatment
Get 20 C57 mices (male and female dual-purpose, body weight 18-22g is available from the Shanghai Experimental Animal Center), all subcutaneous vaccination concentration of every mice is 1 * 10
7The Hep1-6 hepatoma carcinoma cell of/ml; Grow the tumor that diameter is 1-2cm after 16 days in the mice body.Be divided into two group with mice this moment, i.e. matched group and treatment group, 10 every group.From the 17th day treatment group mouse peritoneal injection salvianolic acid B solution, once a day, dosage was 100mg/kg (concentration of salvianolic acid B solution is 5mg/ml, prepares with normal saline); Control group mice lumbar injection every day isometric(al) normal saline once in contrast.As shown in Figure 2, the result shows that the life span of treatment group mice prolongs.
Embodiment 4
Red acetic acid B is to the effect of zoochemistry inductivity tumor treatment
36 Wistar rats (male and female dual-purpose, body weight 180-220g is available from the Shanghai Experimental Animal Center) are divided into three groups, i.e. normal control group, model control group and salvianolic acid B treatment group, 12 every group.Before the formal experiment beginning, give model control group earlier and salvianolic acid B treatment group rat was drunk 0.01% diethylnitrosamine solution 3 months, bring out the purpose that produces tumor in the body to reach; And normal rats still gives normal diet during this period.After the modeling success, each group rat is handled: 1. normal control group: intraperitoneal injection of saline: 2. tumor matched group: intraperitoneal injection of saline according to following method; 3, salvianolic acid B treatment group: lumbar injection concentration is the salvianolic acid B solution of 5mg/ml, and once a day, dosage is 50mg/kg (salvianolic acid B solution adopts the normal saline preparation).Treat after 30 days blood is got in each group rat execution, detect serum albumin (albumin in the blood, ALB), glutamate pyruvate transaminase (alanine aminotransferase, ALT), γ one glutamyl transpeptidase (γ-glutamyltransferase, γ-GT), alkali phosphatase (alkaline phosphatase, content ALP).As shown in Figure 3, the result shows that the laboratory indexes of salvianolic acid B treatment group is clearly better than the tumor matched group.