CN107661348A - Purposes of the sodium acid carbonate as tumor - Google Patents

Purposes of the sodium acid carbonate as tumor Download PDF

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Publication number
CN107661348A
CN107661348A CN201610616769.5A CN201610616769A CN107661348A CN 107661348 A CN107661348 A CN 107661348A CN 201610616769 A CN201610616769 A CN 201610616769A CN 107661348 A CN107661348 A CN 107661348A
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China
Prior art keywords
sodium acid
acid carbonate
medicine
tumor
tumour
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CN201610616769.5A
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Chinese (zh)
Inventor
胡汛
晁明
吴昊
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Zhejiang University ZJU
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Zhejiang University ZJU
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides purposes of the sodium acid carbonate in tumor is prepared, and sodium acid carbonate molecular formula is NaHCO3.Research confirms that sodium acid carbonate can cause neoplasm necrosis or suppress tumour growth, sodium acid carbonate, which has, suppresses tumor neovasculature effect, the medicine for treating tumor vessel embolism can be prepared, tumor vessel embolism chemical therapeutic medicine is prepared, prepares the medicine being intubated for tumour in Embolization and tumour intubation Embolization.The concentration of sodium acid carbonate is 1 10%.Prepared medicine contains the drug excipient or carrier of preparation permission.The present invention develops sodium acid carbonate and is preparing the new application of tumor;It is and non-toxic to human body in knurl vivo medicine-feeding.Therefore sodium acid carbonate can prepare tumor, can reduce treatment price.

Description

Purposes of the sodium acid carbonate as tumor
Technical field
The invention belongs to medicinal usage, it is related to the new medicine use of sodium acid carbonate, more particularly to sodium acid carbonate is treated preparing Purposes in tumour medicine.
Background technology
The molecular formula of sodium acid carbonate is NaHCO3.The pharmacological action of sodium acid carbonate includes:(1) metabolic acidosis is treated, Carbonate concentration in blood plasma is raised, hydrogen ion is neutralized, so as to correct acid poisoning;(2) alkalized urine, due to carbonate in urine PH value raises after concentration increase, makes uric acid, sulfa drugs and hemoglobin etc. be not easy to form crystallization or aggregation in urine;(3) Relieving haperacidity, during orally energy is rapid and/or hydrochloric acid in gastric juice is buffered, without directly affecting gastric acid secretion.Thus pH raises rapidly the high stomach of alleviation in stomach Symptom caused by acid.
The content of the invention
It is an object of the present invention to provide purposes of the sodium acid carbonate in tumor is prepared, sodium acid carbonate English Entitled sodium bicarbonate, molecular formula NaHCO3, in preparation causes neoplasm necrosis, the medicine for suppressing tumour growth Application.The concentration of sodium acid carbonate is 1-10% (mass/volume).Research confirms that sodium acid carbonate can cause neoplasm necrosis or suppression Tumour growth.
Research shows that sodium acid carbonate, which has, suppresses tumor neovasculature effect, can prepare destruction tumor vessel, prepare Suppress the application in tumor neogenetic blood vessels medicine.Sodium acid carbonate can prepare for treat tumor vessel embolism medicine in should With.Application of the sodium acid carbonate in tumor vessel embolism chemical therapeutic medicine is prepared.Answering especially in liver cancer arterial embolization is prepared With.
It is a further object to provide sodium acid carbonate to prepare for the medicinal usage in tumour intubation Embolization. The form of medication of the medicine is drug administration by injection.The concentration of sodium acid carbonate is 1-10% (mass/volume).
Above-mentioned prepared medicine contains the drug excipient or carrier of preparation permission.
Beneficial effects of the present invention have:(1) develop sodium acid carbonate and prepare the new application of tumor;(2) exist Knurl vivo medicine-feeding is non-toxic to human body.Therefore sodium acid carbonate can prepare tumor, can reduce treatment price.
Brief description of the drawings
Fig. 1:Sodium acid carbonate suppresses the growth of 4T1 tumours.After mouse inoculation tumour, every three days measurement mouse weights and The size of knurl.Tumor size uses vernier caliper measurement, measures two parameters of its maximum gauge (L) and minimum diameter (W), tumour Volume calculation uses V=L × W × W/2.
Fig. 2:Sodium acid carbonate suppresses the growth of 4T1 tumours.Mouse inoculation tumour peels off tumour after 3 weeks, weighs.
Fig. 3-1:Sodium acid carbonate increases the necrosis of 4T1 tumours.The tumour peeled off in Fig. 2 is cut in half, visible carbonic acid in figure Hydrogen sodium treatment group transplantable tumor has more necrotic areas compared with control group.Tumour cross section is illustrated, dark border zone marker is horizontal The necrotic area observed on section.On, sodium acid carbonate group, show the cross sections of 4 tumours;Under, control group, show the horizontal strokes of 4 tumours Section.
Fig. 3-2:Sodium acid carbonate increases the necrosis of 4T1 tumours.The statistics area of diagram 3-1 necrotic area.
Embodiment
The present invention is further described in conjunction with the accompanying drawings and embodiments.
Embodiment one:Sodium acid carbonate promotes the death of tumour cell in sugar-free culture-medium.
For entity tumor because vascular system is disorderly, the glucose content in tumour is very low, often in sugared state is lacked, is lacking sugar Under state, death of neoplastic cells.However, lactic acid content is very high in entity tumor, lactic acid protects tumour cell in the case where lacking sugared situation Existence.If improving the pH in tumour, lactic acid environment is destroyed, death may occur for the tumour cell lacked under sugared situation.
Experimental method:Tumor cell line derives from institute of oncology of Zhejiang University.Human liver cancer tumour cell (HepG2), Human prostata cancer tumour cell (PC3), gastric carcinoma cells (SGC), human breast cancer cell (Bcap37 and MCF7), cultivate in sugar-free RPMI-1640 culture mediums in (contain 10% hyclone, 20mM lactic acid).Control group is not added with sodium acid carbonate, and experimental group adds Upper sodium acid carbonate (ultimate density 1.28%).Culture determines the relative survival rate of cell after three days, with trypsin digestion cell, Cell is counted with cell counting count board under microscope.Survival rate calculates:The survival rate for providing control group is 100%, experimental group Survival rate be=(the cell number ÷ cellular control units number of experimental group) x100%.
Experimental result:In sugar-free culture-medium, relative and control group, the survival rate of sodium acid carbonate group is only 10% effect (being shown in Table 1), illustrate that sodium acid carbonate can kill the tumour cell under the conditions of sugar-free.
Table 1
Embodiment two:Sodium acid carbonate promotes the death of sugar-free culture-medium Endothelial Cell.
Principle:The growth of experimental tumor relies on the growth of blood vessel, and the vascular endothelial cell of intra-tumor relies on glucose.Entity Intra-tumor glucose content is very low, and often in sugared state is lacked, in the case where lacking sugared state, vascular endothelial cell is dead.However, entity swells Lactic acid content is very high in knurl, and lactic acid protects vascular endothelial cell to be survived in the case where lacking sugared situation.If improving the pH in tumour, destroy Lactic acid environment, the vascular endothelial cell lacked under sugared situation may occur death, can not form new vessels.
Experimental method:Human vascular endothelial HUVEC derives from institute of oncology of Zhejiang University.HUVEC is cultivated in sugar-free RPMI-1640 culture mediums in (contain 10% hyclone, 20mM lactic acid).Control group is not added with sodium acid carbonate, and experimental group adds Upper sodium acid carbonate (ultimate density 1.28%).Culture determines the relative survival rate of cell after three days, with trypsin digestion cell, Cell is counted with cell counting count board under microscope.Survival rate calculates:The survival rate for providing control group is 100%, experimental group Survival rate be=(the cell number ÷ cellular control units number of experimental group) x100%.
Experimental result:In sugar-free culture-medium, relative and control group, the survival rate of sodium acid carbonate group is only 10% effect (being shown in Table 2), illustrate that sodium acid carbonate can kill the vascular endothelial cell under the conditions of sugar-free.
Table 2
Embodiment three:Sodium acid carbonate causes neoplasm necrosis, suppresses tumour growth
Experimental method:After mouse receives, 6 after packing, are normally raised 3 days per cage, during which daily to make it adapt to environment Change water once, the feed of addition in every three days.Before inoculated tumour cell, mouse weight is weighed, selects the close mouse of body weight.Training Support 4T1 cells (institute of oncology of Zhejiang University) to cell and be in exponential phase, and 80% covers with Tissue Culture Flask.Pancreatin disappears Change cell after 5 minutes, add the fresh culture 10ml containing 10% hyclone, neutralize pancreatin, and 5 points are centrifuged in 1000rpm Clock.Collect sedimentation cell.Cell is washed with the PBS solution of precooling three times, every time centrifugation 5 minutes, to remove completely in culture medium Serum composition.Cell is resuspended in the serum free medium of precooling, counts, cell density is adjusted into 106/ml.Cell hangs Liquid is placed on ice until animal inoculation pvaccination.
With 1ml syringes subcutaneous vaccination 105Cell is to mouse upper limbs oxter.And existed with 5% picric acid/ethanol solution Marked on every mouse skin.
The mouse for being inoculated with oncocyte was grouped at random in second day, every group 10.After one week, tumour can understand Touch (about mung bean is big).100 μ l physiological saline, treatment group injection every other day is subcutaneously injected in tumour periphery for control group 100ul5%NaHCO3(Sigma Co., USA).With the growth of tumour, it is big to grow to about 10mm × 10mm in treatment group tumour Hour, increase injection volume to 300ul.
The size of an every three days mouse weights of measurement and knurl.Tumor size uses vernier caliper measurement, and it is maximum to measure it Two parameters of diameter (L) and minimum diameter (W), gross tumor volume calculation use V=L × W × W/2.
After three weeks, terminate experiment.Careful separation goes out tumour, weighs knurl weight.
Tumour is taken pictures, and is cut in half tumour, photographs to record inside tumor necrosis situation.
Experimental result:As a result referring to Fig. 1, Fig. 2, Fig. 3-1 and Fig. 3-2.Fig. 1 result shows:Sodium acid carbonate group mouse moves The growth rate for planting knurl is considerably slower than control group.Fig. 2 result show the weight of sodium acid carbonate group mice-transplanted tumor significantly less than Control group, illustrate that sodium acid carbonate can suppress the transfer of tumour cell.Fig. 3-1 and Fig. 3-2 result shows sodium acid carbonate group mouse Downright bad area is noticeably greater than control group in transplantable tumor, illustrates that sodium acid carbonate can cause the necrosis of tumour.
Example IV:The effect of sodium acid carbonate is in hepatocellular carcinoma nutrient artery Embolization
Clinical protocol:Patient is preoperative to clarify a diagnosis by EASL (European Liver Research Association) standard, using Child-Pugh Method row liver function scores and classification, and therapeutic scheme is determined with therapeutic strategy by stages in accordance with BCLC (Barcelona liver cancer).TACE arts Performed by the accurate embolism standard of super-selective.3Fr microtubulars insert each branch tumour nutrient artery and hepatocellular carcinoma are suffered from by several times Person is irrigated with sodium acid carbonate, and then tumour nutrient artery thoroughly stops.Postoperative 4-6 weeks check liver dynamic Enhanced MR of patient TACE (magnetic resonance) and arteria hepatica DSA judge the residual tumor situation in two kinds of different therapy regions.18 patients after treatment, tumour Necrosis rate reaches more than 50%.
The embodiment explanation of in vitro and in vivo above:Sodium acid carbonate can kill tumour cell and vascular endothelial cell, suppression Tumour growth processed, and the clinical treatment of tumour can be applied to.It is a kind of safely effectively oncotherapy means.

Claims (4)

1. a kind of purposes of sodium acid carbonate in tumor is prepared, the entitled sodium of sodium acid carbonate English Bicarbonate, molecular formula NaHCO3, it is characterised in that prepare the medicine for causing neoplasm necrosis, suppress tumour growth Application in medicine, the medicine for treating tumor vessel embolism, the tumor neovasculature medicine of suppression, the concentration of sodium acid carbonate is 1- 10%.
A kind of 2. purposes of the sodium acid carbonate according to claim 1 in tumor is prepared, it is characterised in that Prepare the medicine for tumor vessel Embolization, the medicine for tumor vessel embolism chemical therapeutic, for liver cancer HAE Medicine, for the application in the medicine of liver cancer arterial cannulation Embolization, the concentration of sodium acid carbonate is 1-10%.
3. application according to claim 1 or 2, it is characterised in that the medicine that prepared medicine contains preparation permission is assigned Shape agent or carrier.
4. application according to claim 2, it is characterised in that the form of medication of the medicine is drug administration by injection.
CN201610616769.5A 2016-07-29 2016-07-29 Purposes of the sodium acid carbonate as tumor Pending CN107661348A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103316035A (en) * 2012-07-03 2013-09-25 浙江大学 Use of sodium bicarbonate in preparation of medicines for treating cancer

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103316035A (en) * 2012-07-03 2013-09-25 浙江大学 Use of sodium bicarbonate in preparation of medicines for treating cancer

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Application publication date: 20180206

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