CN101214234A - Application of alpha-hydroxy-acid in preparing cancer and tumor in vivo injection therapeutic medicine - Google Patents
Application of alpha-hydroxy-acid in preparing cancer and tumor in vivo injection therapeutic medicine Download PDFInfo
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- CN101214234A CN101214234A CNA2008100325258A CN200810032525A CN101214234A CN 101214234 A CN101214234 A CN 101214234A CN A2008100325258 A CNA2008100325258 A CN A2008100325258A CN 200810032525 A CN200810032525 A CN 200810032525A CN 101214234 A CN101214234 A CN 101214234A
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Abstract
The present invention relates to the medicine technical field and concretely indicates an application of alpha-hydroxy acid for preparing a cancerous tumour internal injection treatment drug. The alpha-hydroxy acid of the present invention indicates hydroxyacetic acid or alpha-hydracrylic acid. With the present invention, the hydroxyacetic acid aqueous solution with different concentrations is prepared to be processed for medicine efficacy tests such as a naked rat experiment, a rat experiment and a cell test, which are compared with the medicine efficacy of electropositive medicine acetic acid used for liver cancer internal injection which has the same concentration with the hydroxyacetic acid aqueous solution. The naked rat experiment and a rat liver damnification experiment show that under the same concentration, the hydroxyacetic acid has similar anti-liver-cancer effect as and even better anti-liver-cancer effect than the acetic acid. The cell test shows that the hydroxyacetic acid is applied to the tumour internal injection with great inhibiting effect towards hepatic tumour, pulmonary tumour, oesophagus tumour, etc. The present invention also approves that the alpha-hydracrylic acid (lactic acid) has similar anticancer effect as the hydroxyacetic acid. The present invention provides the novel cancerous tumour internal injection treatment drug which has strong inhibiting effect towards tumour cells, such as the hepatic tumour, the pulmonary tumour, the oesophagus tumour, etc.
Description
Technical field
The present invention relates to medical technical field, be specifically related to 'alpha '-hydroxy acids application in the injection therapeutic medicine in preparation carcinoma body.
Background technology
Primary hepatocarcinoma (abbreviation hepatocarcinoma) is one of higher common cancer of grade malignancy, and (Hepatocellular carcinoma is main HCC) with hepatocarcinoma.So far hepatectomy is still the optimal treatment method of treatment hepatocarcinoma, but because primary hepatocarcinoma morbidity concealment, development is quick, and the excision person that can perform the operation when making a definite diagnosis only is about 10%, even perform a surgical operation, still have many cases to excise fully or tumor is difficult to avoid postoperative recurrence.For advanced liver cancer, how can't perform the operation because of hepatic insufficiency.This a part of patient needs to treat by the method for various non-excisions, and the non-operative treatment of perhaps going ahead of the rest allows lump dwindle limitation, capable again surgical resection therapy, and promptly the second phase excision can make patient obtain benefit preferably.The non-operative treatment of hepatocarcinoma comprises topical therapeutic, chemotherapy, radiotherapy, immunization therapy and the gene therapy of tumor.Because the development of iconography, the interventional therapy of hepatocarcinoma is considered to non-operative treatment most widely used at present, that effect is best, effect is significantly better than systemic chemotherapy, and part patient still can obtain the chance of secondary operation excision.
Injection for curing is the common a kind of of the outer interventional therapy of hepatocarcinoma blood vessel in the percutaneous hepatocarcinoma tumor body, mainly contain following several Therapeutic Method: 1, anhydrous alcohol injection (PEIT) treatment small liver cancer, promptly the percutaneous liver is worn injection anhydrous alcohol treatment hepatocarcinoma under ultrasonic or CT guiding, its mechanism is to utilize the consolidation of anhydrous alcohol to little blood vessel in the protein denaturation of cancerous cell and dehydration and the cancer, reaches therapeutic purposes and kill cancerous cell safely and effectively.Chinese scholars is consistent thinks the hepatocarcinoma of right≤3cm, and therapeutic effect can compare favourably with operation.Its shortcoming is that side reactions such as pain, heating and the property crossed a transaminase rising can appear in the patient, part patient is to ethanol allergy, and deepening continuously along with applied research, find that the ethanol penetrating power is limited, need heavy dose of and repeatedly the injection of multi-section position just can make complete tumor necrosis, this has just increased the probability that various side reactions and complication take place inevitably.Percutaneous intratumor injection hyperthermal distilled water (PHDI) is to use syringe to extract ebullient distilled water and evenly injected in the tumor in 30～60 seconds rapidly, utilize high-temperature effect, make protein synthesis obstacle in the cancerous cell, thereby kill cancerous cell, the hypotonic characteristic of distilled water causes cancerous cell swelling even disintegrate death, safe, nonirritant own and toxicity, applied widely.Its indication mainly is the hepatocarcinoma tuberosity of diameter≤3cm.Effect and PEIT are suitable, and its shortcoming is the controllability of deactivation cancerous cell and completeness is not good enough and needle track has the possibility of scald.2, yttrium one 9O, phosphorus 1, holmium 1 etc. also can be used for the intratumor injection treatment, and it is that pure beta ray exists with the glass microsphere form, can be expelled to equably in the whole tumor body, and local deactivation oncocyte is reliable, and curative effect is outstanding.But because of it belongs to radionuclide, this method will have the medical protection measure to catch up with, and adds problems such as medicine-feeding source supply, and its clinical practice is restricted.3, percutaneous acetic acid injection (PAI) is that percutaneous puncture enters that injection acetic acid destroys tumor tissues to reach the therapeutic purposes of local deactivation in the liver tumor under ultrasonic or CT guiding.(referring to document Ohnishi K, Ohyama N, ho S, et al.Smallhepatoeellular carcinoma:treatment with as-guided intratumoral injection of aceticacid.Radiology, 1994,193:747) by acetic acid, ethanol zoopery comparative study, show that from the pathological examination of light microscopic, Electronic Speculum acetic acid is non-cell-specific to the destruction of liver, mainly by two approach performance damage effects: the one, after disperse enters cell, utilize the inherent character of acid, directly cause proteinic solidifying; The 2nd, directly destroy membranous structure, influence the permeability of film, accelerated solidification is downright bad to be formed.The indication scope of PAI is more extensive: (1) primary hepatocarcinoma, the treatment of hepatic metastases tumor, it is generally acknowledged that the focus number is no more than 3, maximum focus diameter is no more than small liver cancer curative effect the best of 3cm, also be suitable for diameter＞3cm, the treatment of the median size hepatocarcinoma of＜7cm is (referring to document Ohnishi K, Yoshioka H, ho S, et al.Treatment of nodular hepatoeellular carcinoma larger than 3cm withultrasound-gu ided pe rcutaneous aceticacid injection.Hepatology, 1996,24:1379; Lu Kingdom's honor, Li Xinfeng, Wang Jingyi, etc. ultrasonic guidance percutaneous acetic acid injection for curing hepatocarcinoma new method. Chinese ultrasonic image is learned magazine, and 1999,8:229; Zhou Yicheng, Yang Huafen, Zhang Junxian, etc. the preliminary report radiology practice of liver tumor chemical ablation treatment, 2001,16:73); (2) treatment before the operation helps excision, and can reduce the probability of tumor recurrence, transfer; (3) treatment of the recurrence behind the tumor resection.
Summary of the invention
The purpose of this invention is to provide and a kind of tumor cells such as liver tumor, lung tumor, esophageal neoplasm are all had injection therapeutic medicine in the strong inhibiting new carcinoma body.
The invention provides 'alpha '-hydroxy acids application in the injection therapeutic medicine in preparation carcinoma body.
'alpha '-hydroxy acids of the present invention specifically refers to hydroxyacetic acid or α-Qiang Jibingsuan.
The molecular formula of hydroxyacetic acid is C
2H
4O
3, be a kind of water miscible solid.The Chemical cleaning that is used at present removing rust and incrustation scale more; In cellulosic fabric, be used as cross-linking agent; In woolen dyed, make dyeing auxiliaries; Succedaneum as mineral acid in tanning industry is made high leather; In dermatosis to acne, senile plaque, wart, the treatment that smoothes away wrinkles; The synthesis material that is used to remove dead bark and fine hair agent and fruit acid as skin care item; In producing polylactic acid-glycollic acid (PLGA) is a kind of important biodegradation material; Can be used as some important chemical products such as raw material synthesizing glycol, glyoxalic acid.
Invention has prepared the hydroxy acid solution of variable concentrations, has carried out the tests of pesticide effectiveness such as nude mice experiment, rat experiment and test cell line, and itself and drug effect with the positive drug acetic acid that is used for the hepatocarcinoma intratumor injection of concentration are compared.By the hepatic injury experiment of nude mice experiment and rat, find to have similar even than the better anti-liver tumor effect of acetic acid with acetic acid with hydroxyacetic acid under the concentration.By cell experiment, find that hydroxyacetic acid is used for intratumor injection the tumor cell of liver tumor, lung tumor, esophageal neoplasm etc. is all had powerful inhibitory action.
The acetic acid injection has more powerful destruction to the liver tumor tissue than anhydrous alcohol as the anticarcinogen of now having used clinically, is considered to be used at present a kind of preferably anticarcinogen of hepatocarcinoma intratumor injection.But, in injection process, can cause more violent pain to patient because acetic acid volatilization zest is very strong.And acetic acid is as a kind of acidic liquid, and difficulty is made and can be reduced irritating preparation to patient.Adopt 50% acetic acid according to recommendations such as Ohnishi, injected dose is taked on a small quantity, multiple injection, i.e. 1～2cm tumor, 1～2ml/ time, 2～3cm tumor, 2～3ml/ time, 2-3 time/week, per injection all can bring misery to patient, but this is again inevitable in treatment hepatocarcinoma process.
Comparatively speaking, hydroxyacetic acid is just much better.At first its aqueous solution does not have the so strong volatilization zest of acetic acid, in nude mice experiment by injection process in the reaction of Mus show that also the zest of hydroxyacetic acid is little.And hydroxyacetic acid is a kind of water miscible solid, than being easier to make preparation, with its preparation that makes as functional component such as aqueous solution, microsphere, microcapsule, clathrate etc., particularly make the effect that to play further alleviation patient pain behind the microsphere, and because the slow releasing function of microsphere, can reduce frequency injection, curative effect is lasting stability more; Hydroxyacetic acid is extensive at present capsule material polyglycolic acid (PGA) the preliminary degradation product in vivo as biodegradable microsphere, and its safety has obtained confirming widely.
α-Qiang Jibingsuan is a lactic acid, and molecular formula is C
3H
6O
3, the anticancer effect similar to hydroxyacetic acid arranged through the zoopery proof.
The present invention proved 'alpha '-hydroxy acids and with 'alpha '-hydroxy acids as functional component, the preparation of making according to a conventional method can be used as a kind of new anticarcinogen that is used for injection in the carcinoma.
Description of drawings
Fig. 1 is the tumor growth change curve comparison diagram of injection 15% hydroxyacetic acid and acetic acid.
Fig. 2 is the tumor growth change curve comparison diagram of injection 30% hydroxyacetic acid and acetic acid.
Fig. 3 is the tumor growth change curve comparison diagram of injection 15%, 20%, 30% hydroxyacetic acid.
Fig. 4 is the nude mice photo of 15% acetic acid injection back the 2nd day (A) and the 6th day (B).
Fig. 5 is the nude mice photo of 15% hydroxyacetic acid injection back the 2nd day (A) and the 6th day (B).
Fig. 6 is the nude mice photo of 30% acetic acid injection back the 2nd day (A) and the 6th day (B).
Fig. 7 is the nude mice photo of 30% hydroxyacetic acid injection back the 2nd day (A) and the 6th day (B).
Fig. 8 is injection 15% acetic acid (A) and hydroxyacetic acid (B) back tumor tissue light microscopy checking result, wherein A: still have tumor tissue to have B behind the injection acetic acid: the downright bad part of tumor tissue behind the injection hydroxyacetic acid.
Fig. 9 is tumor tissue light microscopy checking result, wherein A behind injection 30% acetic acid: downright bad periphery shows inflammatory reaction, B: downright bad periphery has granulation tissue to form C: the epidermis of downright bad periphery is normal substantially, D: the muscular tissue of downright bad periphery.
Figure 10 is tumor tissue light microscopy checking result, wherein A behind injection 30% hydroxyacetic acid: obvious necrosis is also seen at downright bad edge, B: downright bad obviously companion calcification, C: downright bad periphery has a large amount of inflammatory cell companion calcifications, D: the rarely seen cell outline of slough.
Figure 11 is the inhibition curve chart of acetic acid to tumor cell of liver strain 7721.
Figure 12 is the inhibition curve chart of hydroxyacetic acid to tumor cell of liver strain 7721.
Figure 13 is 15% lactic acid injection back the 2nd day (A) and the nude mice of 15% hydroxyacetic acid injection back the 2nd day (B) photo relatively.
The specific embodiment
The invention will be further described below in conjunction with embodiment, but enforcement of the present invention is not limited in this.
Hydroxyacetic acid and acetic acid are with the conversion of concentration: because hydroxyacetic acid is a solid, and acetic acid is liquid.So in order to carry out the comparison with concentration, we use mol/L as concentration unit.
The experiment of embodiment 1 nude mice
Select for use nude mice people liver cancer tissue model (SMMC-LTNM in 255 generations, is provided by Jiading District Central Hospital, Shanghai) and 4-6 the week age, the male BALB/C nude mice of body weight 18～20 g.
The back subcutaneous transplantation tumor of SMMC-LTNM fresh do not had downright bad piece of tissue be cut into the homogenate shape, inhale people's syringe 0.2ml with No. 16 syringe needles, it is subcutaneous that tumor tissue is injected another nude mice back, the formation subcutaneous transplantation.Measure the gross tumor volume size every day in required time when treating that its slow absorption begins to grow again about 2-3 week, and the tumor bulk measurement is with major diameter (A) of vernier caliper measurement tumor body and minor axis (B).Gross tumor volume is V (mm
3)=∏ A * B
2/ 6, be that 0.6 ± 0.05cm is for becoming the tumor inclusion criteria with gross tumor volume.
Selected the hydroxyacetic acid (the hydroxyacetic acid solid is available from Beijing coupling Science and Technology Ltd.) of 15%, 20%, 30% 3 concentration that nude mice tumor body is injected respectively.15%, 20% group respectively at the 1st day the injection the first pin 0.1ml, the 5th day the injection the second pin 0.1ml.30% group of the 1st day injection first pin 0.1ml is because the visible blackening incrustation of the most of tumor body in injection back, so only injected 0.05ml at the 5th day.Make 15%, 30% acetic acid simultaneously and made positive control with it, respectively at the 1st day injection first pin 0.1ml, the 5th day injection second pin 0.1ml.Measure tumor body major diameter and and minor axis with precimeter every day. calculate tumor body volume by the gross tumor volume formula.Hydroxyacetic acid group and acetic acid group nude mice were all put to death in the 10th day, and all nude mices are all cooked system and cut open inspection, got tumor, the cardiopulmonary hepatic and renal tissue is done the pathology inspection, paraffin embedding, HE dyeing, the variation of observation of cell and organizational structure under the light microscopic.
The result: the tumor growth change curve comparison diagram of 15% and 30% time injection hydroxyacetic acid and acetic acid is seen Fig. 1 and Fig. 2 respectively.15%, the tumor growth change curve comparison diagram of the hydroxyacetic acid under 20%, 30% 3 concentration is seen Fig. 3.Nude mice is put to death the light microscopy checking of back tumor tissue and sees Fig. 4,5,6.
The equal well-grown of the nude mice of hydroxyacetic acid group and acetic acid group.After the nude mice injection by 15% and 30% time hydroxyacetic acid group and acetic acid group, the acetic acid group nude mice has more obviously violent reaction of struggling compared with hydroxyacetic acid group nude mice.Injection back hydroxyacetic acid group forms a scab obviously than the big color of tumor blackening scope of acetic acid group is dark and local, and hydroxyacetic acid is bigger than the slope of acetic acid as can be seen by tumor growth change curve comparison diagram, and tumor is dwindled obviously.The light microscopic result of the longitudinal section of 15% hydroxyacetic acid and acetic acid tumor shows: each cardiopulmonary hepatic and renal tissue section of organizing nude mice there is no unusual.In the whole tumor tissues of acetic acid group 60% necrosis is arranged, hydroxyacetic acid is then downright bad fully, the rarely seen cell outline of slough.The light microscopic result of the longitudinal section of 30% hydroxyacetic acid and acetic acid tumor shows: the whole tumor tissues of acetic acid group only has partial necrosis, and visible downright bad periphery has granulation tissue to form and can see muscular tissue.The hydroxyacetic acid group is then downright bad fully, and downright bad obviously companion calcification, and obvious necrosis is also seen at downright bad edge, and periphery has a large amount of inflammatory cell companion calcifications.As can be known from the above results, with than acetic acid effective of hydroxyacetic acid under the concentration to tumor treatment.
To the comparison of tumor treatment effect, find: along with the increase of concentration, the tumor blackening of nude mice is bigger, and tumor is dwindled also more obvious for hydroxyacetic acid under 15%, 20%, 30% 3 concentration.Again according to the om observation result, though the tumor after 15% group of hydroxyacetic acid with 30% group is injected is all downright bad fully, but can see downright bad obviously companion calcification under the light microscopic of 30% group hydroxyacetic acid, the hydroxyacetic acid of 30% group hydroxyacetic acid than 15% group makes the degree of necrosis of tumor bigger as can be known.To sum up can draw: along with the increase of concentration, hydroxyacetic acid strengthens the tumor treatment effect.
With rat with 10% chloral hydrate intraperitoneal anesthesia after, xiphoid-process is made down a little otch, going into behind the abdominal cavity is visible rat liver. in liver, directly inject 15% hydroxyacetic acid 50ul, close abdomen then.Other injects Hepar Mus with 15% acetic acid 50ul, as positive controls.Diameter from cardinal principle specimen formation necrosis region compared with Mus execution in the 4th day in the injection back.
Found that hydroxyacetic acid can cause Hepar Mus injection site generation coagulation necrosis, point out it can be used for local injection treatment hepatocarcinoma.And the necrosis region that rat liver is formed by acetic acid and hydroxyacetic acid as can be seen, and hydroxyacetic acid has the effect similar to acetic acid.
The vitro inhibition effect of embodiment 3 tumor cell of liver
Cell culture: tumor cell of liver strain 7721 (available from Chinese Academy of Sciences's cell bank), with the DMEM culture medium (containing penicillin 100 μ g/ml and streptomycin 100 μ g/ml) that contains 10% new-born calf serum at 37 ℃, 5%CO
2Hatch in the cell culture incubator, the cell of the trophophase of taking the logarithm experimentizes.
The vitro inhibition effect of tumor cell: 7721 cell trypsinizations, dispel, adjusting cell concentration is 5 * 10
4/ mL is added on 96 well culture plates, every hole 100 μ L.Put 37 ℃, 5%CO
2, the saturated humidity condition cultivates 24h.Remove culture medium, add 120 μ L fresh cultures, and then add medicine acetic acid and each 30 μ L of hydroxyacetic acid of variable concentrations respectively, blank well and control wells add the culture medium of equivalent, put 37 ℃, 5%CO
2, cultivate 48h under the saturated humidity condition.Adding concentration is the MTT of 5mg/ml, 15 μ L/ holes, 37 ℃, 5%CO
2, the saturated humidity condition hatches 4h.Abandon supernatant, add dimethyl sulfoxide (DMSO) 100 μ L/ holes, about vibration 10min.Put microplate reader and measure trap (A) value, wavelength is 570nm, with reference to wavelength 630nm.Gained data computation IC50.Inhibitory rate of cell growth=(1-test group average A value/matched group average A value) * 100%.Experiment repeats 3 times.
The result: after the acetic acid of variable concentrations and hydroxyacetic acid acted on tumor cell of liver strain 7,721 48 h, along with concentration increases, cell survival rate significantly descended, to growth of tumour cell suppression ratio significantly rise (accompanying drawing 12,13).Begin to do the inhibitory action of acetic acid and hydroxyacetic acid pair cell and the statistical analysis of blank (t check) from low concentration, find when concentration is increased to 25mM, the difference of the two has significance (p＜0.05), and does not have significant difference between the inhibitory action of the two pair cell at this moment.Acetic acid that hence one can see that is identical to the minimum inhibitory concentration of tumor cell of liver strain 7721 with hydroxyacetic acid, and the inhibition degree of the two is identical.With the analysis (t check) that takes statistics between the inhibitory action to acetic acid and hydroxyacetic acid pair cell under the concentration, the two does not all have significant difference to the result under each concentration.Half cell amount of suppression (IC50 value) acetic acid and the hydroxyacetic acid of tumor cell of liver strain 7721 all are 26mM.
The vitro inhibition effect of embodiment 4 lung tumor cells
With the DMEM culture medium (containing penicillin 100 μ g/ml and streptomycin 100 μ g/ml) that contains 10% new-born calf serum at 37 ℃, 5%CO
2Hatch in the cell culture incubator, the cell of the trophophase of taking the logarithm experimentizes.Lung tumor cell A549 (available from Chinese Academy of Sciences's cell bank) uses trypsinization, dispels, and adjusting cell concentration is 5 * 10
4/ mL is added on 96 well culture plates, every hole 100 μ L.Put 37 ℃, 5%CO
2, the saturated humidity condition cultivates 24h.Remove culture medium, add 120 μ L fresh cultures, and then add the medicine hydroxyacetic acid 30 μ L of variable concentrations respectively, blank well and control wells add the culture medium of equivalent, put 37 ℃, 5%CO
2, cultivate 48h under the saturated humidity condition.Adding concentration is the MTT of 5mg/ml, 15 μ L/ holes, 37 ℃, 5%CO
2, the saturated humidity condition hatches 4h.Abandon supernatant, add dimethyl sulfoxide (DMSO) 100 μ L/ holes, about vibration 10min.Put microplate reader and measure trap (A) value, wavelength is 570nm, with reference to wavelength 630nm.Experiment repeats 3 times.The result shows that hydroxyacetic acid has the obvious in-vitro suppression effect to lung tumor cell.Point out it to can be used for the pulmonary carcinoma intratumor injection.
Embodiment 5 esophageal neoplasm cells in vitro inhibitory action
Use with the foregoing description 4 in identical method, but with esophageal neoplasm cell Eca-109 (available from Chinese Academy of Sciences's cell bank) replacement lung tumor cell.The result shows that hydroxyacetic acid has the obvious in-vitro suppression effect to the esophageal neoplasm cell.Point out it to can be used for esophageal carcinoma intratumor injection.
Embodiment 6 lactic acid are as the nude mice experiment of anticarcinogen
Select 4-6 age in week for use, the male BALB/C nude mice people liver cancer tissue model of body weight 18～20g forms subcutaneous transplantation.Measure the gross tumor volume size every day in required time when treating that its slow absorption begins to grow again about 2-3 week, and the tumor bulk measurement is with major diameter (A) of vernier caliper measurement tumor body and minor axis (B).Gross tumor volume is V (mm
3)=∏ A * B
2/ 6, be that 0.6 ± 0.05cm is for becoming the tumor inclusion criteria with gross tumor volume.
Select for use the lactic acid (lactic acid is available from Wuxi good fortune Pedicellus et Pericarpium Trapae pharmaceutical Co. Ltd) of 15% concentration that nude mice tumor body is injected.In the 1st day injection first pin 0.1ml, the 5th day injection second pin 0.1ml.Measure tumor body major diameter and and minor axis with precimeter every day. calculate tumor body volume by the gross tumor volume formula.Put to death the nude mice and the system of doing in the 10th day and cut open inspection, get tumor, the cardiopulmonary hepatic and renal tissue is done the pathology inspection, paraffin embedding, HE dyeing, the variation of observation of cell and organizational structure under the light microscopic.
The result: nude mice well-grown behind the injection lactic acid, tumor blackening and local incrustation are obvious, and each cardiopulmonary hepatic and renal tissue section of organizing nude mice there is no unusual.Compare with hydroxyacetic acid, similar anticancer effect (seeing Figure 13) is arranged to it with concentration.
Embodiment 7 lactic acid are as the vitro inhibition effect of anticarcinogen to tumor cell of liver
With the DMEM culture medium (containing penicillin 100 μ g/ml and streptomycin 100 μ g/ml) that contains 10% new-born calf serum at 37 ℃, 5%CO
2Hatch in the cell culture incubator, the cell of the trophophase of taking the logarithm experimentizes.Tumor cell of liver 7721 (available from Chinese Academy of Sciences's cell bank) is used trypsinization, dispels, and adjusting cell concentration is 5 * 10
4/ mL is added on 96 well culture plates, every hole 100 μ L.Put 37 ℃, 5%CO
2, the saturated humidity condition cultivates 24h.Remove culture medium, add 120 μ L fresh cultures, and then add the medicine lactic acid 30 μ L of variable concentrations respectively, blank well and control wells add the culture medium of equivalent, put 37 ℃, 5%CO
2, cultivate 48h under the saturated humidity condition.Adding concentration is the MTT of 5mg/ml, 15 μ L/ holes, 37 ℃, 5%CO
2, the saturated humidity condition hatches 4h.Abandon supernatant, add dimethyl sulfoxide (DMSO) 100 μ L/ holes, about vibration 10min.Put microplate reader and measure trap (A) value, wavelength is 570nm, with reference to wavelength 630nm.Experiment repeats 3 times.The result shows that lactic acid has the obvious in-vitro suppression effect to tumor cell of liver.Point out it to can be used for injection in the carcinoma.
Claims (3)
1. 'alpha '-hydroxy acids application in the injection therapeutic medicine in preparation carcinoma body, 'alpha '-hydroxy acids wherein is hydroxyacetic acid or α-Qiang Jibingsuan.
2. 'alpha '-hydroxy acids according to claim 1 is the application in the injection therapeutic medicine in preparation carcinoma body, and carcinoma wherein is liver tumor, lung tumor or esophageal neoplasm.
3. 'alpha '-hydroxy acids according to claim 1 is the application in the injection therapeutic medicine in preparation carcinoma body, and this medicine is to contain Alpha-hydroxy aqueous acid, microsphere, microcapsule or clathrate.
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| EP3247342A4 (en) * | 2015-01-23 | 2018-10-10 | Temple University - Of The Commonwealth System of Higher Education | Use of short chain fatty acids in cancer prevention |
| CN110870919A (en) * | 2018-08-31 | 2020-03-10 | 成都夸常奥普医疗科技有限公司 | Pharmaceutical composition containing acidifier and anti-tumor chemotherapeutic drug and application thereof |
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| EP3247342A4 (en) * | 2015-01-23 | 2018-10-10 | Temple University - Of The Commonwealth System of Higher Education | Use of short chain fatty acids in cancer prevention |
| US10143669B2 (en) | 2015-01-23 | 2018-12-04 | Temple University—Of the Commonwealth System of Higher Education | Use of short chain fatty acids in cancer prevention |
| US10231941B2 (en) | 2015-01-23 | 2019-03-19 | Temple University—Of The Commonwealth System of Higher Educaton | Use of short chain fatty acids in cancer prevention |
| US11963938B2 (en) | 2015-01-23 | 2024-04-23 | Temple University-Of The Commonwealth System Of Higher Education | Use of short chain fatty acids in cancer prevention |
| CN110870919A (en) * | 2018-08-31 | 2020-03-10 | 成都夸常奥普医疗科技有限公司 | Pharmaceutical composition containing acidifier and anti-tumor chemotherapeutic drug and application thereof |
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