CN101172113A - Application of Tween 80 injection in substance base and thermotherapy for treating tumour - Google Patents
Application of Tween 80 injection in substance base and thermotherapy for treating tumour Download PDFInfo
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- CN101172113A CN101172113A CNA2007101340049A CN200710134004A CN101172113A CN 101172113 A CN101172113 A CN 101172113A CN A2007101340049 A CNA2007101340049 A CN A2007101340049A CN 200710134004 A CN200710134004 A CN 200710134004A CN 101172113 A CN101172113 A CN 101172113A
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Abstract
The invention relates to a processing method to surface active agent Tween 80, and Tween 80 purifying preparation obtained after being processed by the method of the invention. The invention also relates to the application of the Tween 80 preparation during the process of preparing the medicine of thermotherapy enhanced sensitivity agent, and the application during the process of preparing tumour with thermotherapy.
Description
Invention field
The present invention relates to a kind of method that the surfactant Tween 80 is handled, and the Tween 80 preparation that after the inventive method is handled, obtains.The invention still further relates to the application of this Tween 80 preparation in the medicine of preparation thermotherapy sensitizer, and the application in the thermotherapy treatment tumor.
Technical background
Thermotherapy (Thermochemotherapy) treatment tumor is a kind of in recent years new " ancient " method of the treatment cancer that the people paid close attention to that is once again.Itself and operation, radiotherapy, chemotherapy, immunotherapy also claim tumor five big therapies, its the main mechanism of action is that the normal cell of tumor cell is to warm more responsive, have selective killing tumor cell effect, in clinical practice, obtained certain good efficacy at present.
Before the history of thermotherapy can be traced to more than 100 year.As far back as 1866, Bush at first reported 1 routine facial sarcoma patient, and after infecting the erysipelas hyperpyrexia of lasting a few days, facial tumors is dwindled gradually, tumor complete obiteration after 2 years, patient's survival.Coley in 1893 have delivered " fever therapy " (fever therapy) of his research on " JAMA ", be a kind of Whole Body Hypenhermia in essence, with he more coetaneous doctors use clinically do not obtain the cure rate (50%) that resembles Coley and report high.After this thermotherapy experienced very long, Ting Zhibuqian history almost.1962, the Basic of Biology of thermotherapy in oncotherapy established in the clinical and experimentation report of Crile.The development of 1970's along with microwave and ultrasonic technique makes hot Procarbazium obtain leap.
Studies show that: the cell of acute anoxia is insensitive to reacting by heating, and the cell of the chronic hypoxia that metabolic consumption causes is the most responsive to heat.Experiment confirm: normal cell is heated to more than 45 ℃ and just necroses, and tumor cell promptly begins death at 40 ℃～43 ℃.Secular sour environment, the malnutrition chronic hypoxia makes tumor cell strengthen heat sensitivity, and this is a warm determiner controlling cancer.Because the microcirculation of normal structure and tumor tissues is different, tumor tissues microcirculation characteristics are: tumor tissues blood capillary basement membrane is unsound, expansion brokenly, and distortion, narrow, disorder; Tumor tissues is directly invaded blood capillary and is caused the luminal stenosis obturation, causes that blood is for obstacle; Tumor vessel is grown unsound, lacks neural sensor, and is poor to the reflectance of heat.These characteristics cause the tumor vessel exchange capacity poor, and during heating, the normal structure blood flow obviously increases, and heat is in time taken away, and heat radiation is easy, and temperature can obviously not raise; And at the beginning of the tumor tissues heating, blood flow increases, slow down thereupon, tumor tissues heat radiation difficulty, cause heat accumulation in tumor tissue, temperature raises significantly, so heating can act on tumor tissues selectively and not necessarily be damaged to the normal structure of closing on, this is another determiner of hot Procarbazium.
Up to now, a large amount of bases and clinical research are at the biological mechanism that has disclosed thermotherapy in varying degrees.Wherein topmost factor comprises the radiation sensitization and the chemotherapy sensitizing effect of heat tolerance, thermotherapy dosage and thermotherapy of blood flow, the tumor cell of pH value, the tumor of tumor.
Thermotherapy has following characteristics: (1) warm selectively acting is in tumor cell; (2) different with radiation and chemotherapy, but the anoxic cell of killing tumor cells; (3) tumor is warm when low pH value a bigger lethal effect; (4) and with radiotherapy synergism is arranged, the easier S phase cell of resisting radiation of killing.
But simple thermotherapy has certain limitation: experiment showed, single hot Procarbazium of use, the interior temperature of tumor must reach certain height and keep the regular hour, could guarantee that tumor cell all is killed.The temperature and time that the kill tumor cell is required is close with the result of cultured cell in vitro, approximately 42 ℃ of need, 2h or 43 ℃, 1h.Because temperature is constantly to change in the heating process, keep the required effective temperature of kill cancer cell, heat time heating time, patient is difficult to stand.And because kind, form, the different sizes of various tumors, same lump center is with different to heat sensitivity on every side, moreover external local thermotherapy is difficult to make deep tumor focus temperature to rise.
And, as above being analyzed, though there are certain difference in normal cell and tumor cell to the critical temperature of heat tolerance, but normal cell and tumor cell differ near (being about 2 ℃) the critical temperature of heat tolerance, so how to improve the sensitivity of tumor cell to heat, so that in an important directions that obtains better therapeutic under the same temperature or (safer like this, for most patient can tolerate) obtained and same curative effect is the current research thermotherapy under higher temperature under lower temperature.
Warm pair cell damages initial target spot at cytoplasma membrane (film that comprises organelle).Cell membrane is by being inlaid with the existing certain fluidity that protein is formed in two lipid molecular layers, the liquid crystal state film that has order again, the integrity of this structure are the essential conditions of keeping cell activities.
Warm-heat effect can cause the movable quickening of the lipid molecular of film, and intermolecular distance strengthens, and the flowability of film is quickened, and permeability changes.When temperature reached certain threshold value, liquid crystal state underwent phase transition, and caused the protein hydrogen bonds instability, caused the reversibility of memebrane protein agent structure and irreversibility to change, and consequently caused the memebrane protein degeneration, came off variations such as dystopy.
Tumor cell is because the carbohydrate metabolism of tumor cell is based on glycolysis to the normal cell height of heat sensitivity, so the normal cell of PH is low in the cell.And the composition of tumor cell membrane is different with normal cell, and the ratio that contains oleic acid and/or polyunsaturated fatty acid in the tumor cell membrane is higher, and cholesterol level is lower, so just makes film forming mobile increase, the stability decreases of film.The normal cell of the liquid crystal of its cytoplasma membrane more becomes very liquid, so tumor cell is responsive more to warm normal cell.
Think that at present some medicines that act on cell membrane can strengthen warm damaging action to tumor cell, mainly think these medicines: 1, act on the cell membrane lipid and cause that membrane structure changes and mobile increasing, influence the ion permeability of film, the stability and the information transmission of film; 2, act on cell membrane protein, cause the memebrane protein degeneration, come off, influence the integral protein on membrane receptor, the film, the function of carrier; 3, suppress the formation of heat tolerance.
In sum, though the mechanism of thermotherapy treatment tumor is understood by educational circles and is accepted extensively at present, make it to be more suitable for clinical practice but how to reduce warm temperature, and selection warm sensitizer effective, that have clinical value is present urgent problem.
The medicine that acts on cell membrane at present can be divided into the medicine that acts on memebrane protein and act on the medicine two big classes of membrane lipid.But the medicine that acts on memebrane protein commonly used, benzaldehyde for example, this class chemicals such as ethanol can't directly be used human body, so it still has very big difficulty as medicinal application.And the medicine that acts on membrane lipid for example local anesthetic, amphotericin B etc. are difficult to use because of certain side effect is arranged.
Research worker of the present invention is found: the adjuvant Tween 80 (polyethenoxy sorbitan acid anhydride list olein) that is commonly used for preparation in the medicine is mixed with emulsifying agent or solution, can be used for increasing the effect of thermotherapy.
Tween 80 is a polyethylene anhydro sorbitol acid anhydride monoleate, be sorbitol once with the second dehydration product.Its molecule includes a plurality of unsaturated ethylene linkages, and concrete molecular formula is:
Owing to comprise hydrophilic polyoxyethylene groups H (C in the molecule
2H
4O)
nO
-, therefore be to use always in a kind of medical science, daily use chemicals and the grocery trade to do solubilising or emulsive additives, at field of medicaments, Tween 80 uses as excipient substances such as the solubilising in injection and other dosage forms, emulsifying agents.
But discover that heavy dose of Tween 80 that uses has certain side effect, particularly intravenously administrable can produce haemolysis when finite concentration.On the other hand, bigger for the dosage of animal and human's application, side effect is also bigger.
Research worker of the present invention is found, handle the effect that the product of back acquisition can improve thermotherapy inhibition tumor by Tween 80 being carried out special process, and have good effect under the human body safe dosage satisfying, thereby overcome the defective of existing warm sensitizer, can effectively be applied to clinical.
Summary of the invention
The object of the present invention is to provide a kind of method for preparing Tween 80 heating therapy sensitizer, the steps include: to get Tween 80 stock solution adds injection water or injection normal saline solution and is diluted to 10% concentration, being heated to 70 ℃ stirred 20 minutes, cooling, filtration, embedding, sterilized 15 minutes for 121 ℃, naturally cool to 70 ℃ of vibrations 20 minutes, naturally cool to room temperature then.
The claimed a kind of thermotherapy sensitizer of the present invention; it is characterized in that: it is that Tween 80 stock solution adds the injection water or the injection normal saline solution is diluted to 10% concentration by getting; being heated to 70 ℃ stirred 20 minutes; cooling, filtration, embedding; sterilized 15 minutes for 121 ℃; naturally cool to 70 ℃ of vibrations 20 minutes, it is preparation-obtained to naturally cool to room temperature then.
Thermotherapy sensitizer as indicated above is characterized in that it can use under the situation of 2 times, 4 times, 8 times, 16 times of dilutions.
The application of the also claimed described thermotherapy sensitizer of the present invention in the thermotherapy sensitizer of preparation treatment tumor.
Application as indicated above is characterized in that described sensitizer can strengthen the tumor killing effect of thermotherapy.
Application as indicated above is characterized in that it is 41 ℃ that described sensitizer can make the critical temperature of thermotherapy.
Application as indicated above is characterized in that the Tween 80 concentration in the sensitizer of effective dose can be 10% to 0.625%.
Application as indicated above is characterized in that described sensitizer can use under the situation of 2 times, 4 times, 8 times, 16 times of dilutions.
A kind of method for preparing the thermotherapy sensitizer, the steps include: to get Tween 80 stock solution adds injection water or injection normal saline solution and is diluted to 0.5%-50% concentration, being heated to 70 ℃ stirred 20 minutes, cooling, filtration, embedding, 121 ℃ of sterilizations were sterilized 30 minutes in 15 minutes or 100 ℃, naturally cool to 70 ℃ of vibrations 20 minutes, naturally cool to room temperature then.
Characteristics of the present invention are:
1. preparation is handled the Tween 80 preparation and the thermotherapy that obtain and can be produced significant synergistic antitumor effect through method of the present invention, can make the required critical temperature of thermotherapy of tumor be reduced to 41 ℃ by 43 ℃ of routine, can effectively carry out tumor treatment.
2. handle the growth that the Tween 80 preparation that obtains can significantly suppress murine melanoma through method preparation of the present invention, have optimum efficiency when wherein the temperature of thermotherapy is 41 ℃.
3. preparation is handled the Tween 80 preparation that obtains with respect to untreated Tween 80 preparation through method of the present invention, the tumour inhibiting rate of preparation of the present invention is apparently higher than undressed Tween 80 preparation, thereby illustrates that the more untreated Tween 80 of product of the present invention has the synergy of higher thermotherapy.
4. test shows, through method of the present invention preparation handle the Tween 80 preparation that obtains can be than promptly obtaining good tumor killing effect under the low dosage, thereby increase substantially its human body application security, eliminate potential haemolysis unsafe factor.
Below in conjunction with specific embodiment, be described in further detail technical scheme of the present invention:
Used reagent, cell, the laboratory animal of the present invention is commercialization and buys, and the experimental technique that is adopted, effect evaluation method also are this area conventional method commonly used, and it should be conventionally known to one of skill in the art, does not therefore repeat them here.
Description of drawings
Product after Fig. 1 handles technology one, two, three carries out the collection of illustrative plates as a result that HPLC analyzes.
The specific embodiment
Embodiment 1: Tween 80 preparation process thereof method
Technology one (0.5%--50% tween stock solution):
Get Tween 80 stock solution and add injection water or injection normal saline solution and be diluted to 0.5%--50% concentration, adopt the degerming of aseptic filtration method then, be prepared into preparation.
Technology two (filtration treatment method):
Get Tween 80 stock solution and add injection water or injection normal saline solution and be diluted to 0.5%--50% concentration, the degerming of aseptic filtration method is adopted in 40 ℃ of insulations 6 hours then, is prepared into preparation.
Technology three (voltolization):
Get Tween 80 stock solution and add injection water or injection normal saline solution and be diluted to 0.5%--50% concentration, be heated to 70 ℃ and stirred cooling, filtration, embedding 20 minutes, sterilized 15 minutes for 121 ℃, naturally cool to 70 ℃ of vibrations 20 minutes, naturally cool to room temperature then, be prepared into preparation.
Embodiment 2: the quality analysis research of different process tween-80 injection
Utilize conventional HPLC analytical technology, analyze handling the product that obtains by three kinds of different process among the embodiment 1, analysis result as shown in Figure 1.
Relatively find by the HPLC collection of illustrative plates:
1) sample dentation peak shape in 10min～20min interval of preparing of adopting process two, three is eliminated substantially, and the characteristic absorption that exists about 25min is compared no significant change than crude drug;
2) technology three is compared with technology two, and oleic absworption peak increases obviously.
3) preparation process three shows that the oleic acid absworption peak strengthens, calculate with normalization method, because the disappearance at peak between the 10min-20min, and make relative oleic acid content increase.
Oleic acid can increase the flowability of cytoplasma membrane under the common assistance of other compositions of Tween 80, therefore increased the sensitivity of cell to temperature.Because the tumor cell membrane fluidity is bigger, so under this PROCESS FOR TREATMENT condition, make tumor cell responsive more to heat.
Embodiment 3: the tumor killing effect experiment of the sensitizer that technology three prepares (voltolization):
1.1 laboratory animal: C
57The BL/6 mice, 48, female, body weight 18～20 grams, Co., Ltd provides by the Si Laike laboratory animal.
1.2 cell culture: mouse melanin tumor cell K111, the conventional cultivation, results logarithm culture period cell, concentration to 10 is adjusted in the counting back
7/ ml.
1.3 experimental technique: vola subcutaneous vaccination 5 * 10 behind mice
5The K111 tumor cell, mice is divided into 6 groups at random after 7 days, 8 every group.1. warm group: mice is placed in 41 ± 0.1 ℃ of water baths, and the mouse tumor foot inserts in the water-bath of deep, heats 100 minutes.2. tween group: mice through tail vein injection Tween 80 (concentration is 10%) 0.2ml/ only.3. actual tween concentration is three warm groups of 10% technologies: mice through tail vein injection Tween 80 (concentration is 10%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.4. actual tween concentration is 5% three warm groups of technologies (2 times of diluents of technology three sensitizers): mice through tail vein injection Tween 80 (concentration is 5%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.5. actual tween concentration is 2.5% three warm groups of technologies (4 times of diluents of technology three sensitizers): mice through tail vein injection Tween 80 (concentration is 2.5%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.6. actual tween concentration is 1.25% three warm groups of technologies (8 times of diluents of technology three sensitizers): mice through tail vein injection Tween 80 (concentration is 1.25%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.7. actual tween concentration is 0.625% three warm groups of technologies (16 times of diluents of technology three sensitizers): mice through tail vein injection Tween 80 (concentration is 0.625%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.8. blank group.
Carried out a thermotherapy experiment (method is the same) again every 7 days.The 4th week put to death mice and calculated every mice foot tumor weight, and was calculated as follows tumour inhibiting rate.
Tumor tumour inhibiting rate %=100%* (the average tumor of the average tumor weight-administration of matched group group is heavy)/the average tumor of matched group is heavy
1.4 result of the test:
First result of the test
| Body weight before the test | Body weight during off-test | Tumor heavy (g) | Tumour inhibiting rate (%) | |
| control | 19.23± 0.73 | 21.20± 2.25 | 0.069 | |
| 10% tween group (technology three)+warm | 18.92± 1.12 | 19.59± 1.44 | 0.0268 | 61.2 |
| 5% tween group (technology three)+warm | 19.03± 1.21 | 20.31± 1.12 | 0.0287 | 58.4 |
| 2.5% tween group (technology three)+warm | 18.89± 0.93 | 20.03± 1.32 | 0.0316 | 54.2 |
| 1.25% tween group (technology three)+warm | 18.72± 0.66 | 21.87± 1.07 | 0.0377 | 45.3 |
| 0.625% tween group (technology three)+warm | 18.92± 0.31 | 21.17± 1.08 | 0.0406 | 41.2 |
| Warm group | 19.53± 1.23 | 21.50± 1.72 | 0.0482 | 30.1 |
| 10% tween group | 18.32± 1.50 | 20.52± 1.52 | 0.0583 | 15.5 |
Second batch of result of the test
| Body weight before the test | Body weight during off-test | Tumor heavy (g) | Tumour inhibiting rate (%) | |
| control | 20.32± 0.95 | 22.52± 1.08 | 0.072 |
| 10% tween group (technology three)+warm | 19.92± 0.85 | 22.15± 1.55 | 0.0290 | 59.7 |
| 5% tween group (technology three)+warm | 18.95± 1.13 | 20.91± 1.63 | 0.0302 | 58.1 |
| 2.5% tween group (technology three)+warm | 18.29± 2.10 | 21.61± 2.01 | 0.0322 | 55.3 |
| 1.25% tween group (technology three)+warm | 18.22± 1.10 | 21.69± 1.36 | 0.0428 | 47.2 |
| 0.625% tween group (technology three)+warm | 19.22± 1.42 | 21.87± 1.56 | 0.0411 | 40.5 |
| Warm group | 19.21± 1.31 | 22.20± 1.65 | 0.0530 | 26.4 |
| 10% tween group | 20.11± 1.15 | 22.14± 0.83 | 0.0625 | 13.2 |
The 3rd batch of result of the test
| Body weight before the test | Body weight during off-test | Tumor heavy (g) | Tumour inhibiting rate (%) | |
| control | 19.32± 0.83 | 21.99± 1.85 | 0.075 | |
| 10% tween group (technology three)+warm | 19.88± 1.32 | 21.89± 1.54 | 0.0282 | 62.4 |
| 5% tween group (technology three)+warm | 19.83± 1.85 | 22.31± 1.32 | 0.0318 | 57.6 |
| 2.5% tween group (technology three)+warm | 19.55± 0.93 | 22.22± 1.56 | 0.0332 | 55.7 |
| 1.25% tween group (technology three)+warm | 18.97± 1.05 | 21.55± 1.27 | 0.0399 | 46.7 |
| 0.625% tween group (technology three)+warm | 19.33± 1.11 | 22.32± 1.12 | 0.0439 | 41.5 |
| Warm group | 20.53± 1.23 | 21.66± 1.76 | 0.0527 | 29.7 |
| 10% tween group | 19.32± 1.50 | 22.52± 2.11 | 0.0647 | 13.7 |
Embodiment 4: the tumor killing effect experiment of the sensitizer that technology two prepares (filtration treatment method):
2.1 laboratory animal: C
57The BL/6 mice, 48, female, body weight 18～20 grams, Co., Ltd provides by the Si Laike laboratory animal.
2.2 cell culture: mouse melanin tumor cell K111, the conventional cultivation, results logarithm culture period cell, concentration to 10 is adjusted in the counting back
7/ ml.
2.3 experimental technique: vola subcutaneous vaccination 5 * 10 behind mice
5The K111 tumor cell, mice is divided into 6 groups at random after 7 days, 8 every group.1. warm group: mice is placed in 41 ± 0.1 ℃ of water baths, and the mouse tumor foot inserts in the water-bath of deep, heats 100 minutes.2. tween group: mice through tail vein injection Tween 80 (concentration is 10%) 0.2ml/ only.3. actual tween concentration is two warm groups of 10% technologies: mice through tail vein injection Tween 80 (concentration is 10%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.4. actual tween concentration is 5% two warm groups of technologies (2 times of diluents of technology two sensitizers): mice through tail vein injection Tween 80 (concentration is 5%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.5. actual tween concentration is 2.5% two warm groups of technologies (4 times of diluents of technology two sensitizers): mice through tail vein injection Tween 80 (concentration is 2.5%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.6. actual tween concentration is 1.25% two warm groups of technologies (8 times of diluents of technology two sensitizers): mice through tail vein injection Tween 80 (concentration is 1.25%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.7. actual tween concentration is 0.625% two warm groups of technologies (16 times of diluents of technology two sensitizers): mice through tail vein injection Tween 80 (concentration is 0.625%) 0.2ml/ only after 15 minutes, carries out 41 ℃ of thermotherapies (with warm group) again.8. blank group.
Carried out a thermotherapy experiment (method is the same) again every 7 days.The 4th week put to death mice and calculated every mice foot tumor weight, and was calculated as follows tumour inhibiting rate.
Tumor tumour inhibiting rate %=100%* (the average tumor of the average tumor weight-administration of matched group group is heavy)/the average tumor of matched group is heavy
2.4 result of the test:
First result of the test:
| Body weight before the test | Body weight during off-test | Tumor heavy (g) | Tumour inhibiting rate (%) | |
| control | 18.75± 0.71 | 21.93± 1.28 | 0.071 | |
| 10% tween group (technology two)+warm | 20.22± 0.46 | 22.73± 1.10 | 0.039 | 45.3 |
| 5% tween group (technology two)+warm | 19.22± 1.07 | 21.37± 1.09 | 0.043 | 40.1 |
| 2.5% tween group (technology two)+warm | 18.27± 0.39 | 22.47± 2.03 | 0.046 | 35.6 |
| 1.25% tween group (technology two)+warm | 19.33± 0.68 | 21.83± 1.81 | 0.050 | 30.2 |
| 0.625% tween group (technology two)+warm | 20.21± 0.98 | 21.32± 1.23 | 0.052 | 27.4 |
| Warm group | 20.17± 0.77 | 22.11± 1.41 | 0.051 | 28.1 |
| 10% tween group | 19.57± 1.29 | 21.68± 1.17 | 0.059 | 16.3 |
Second batch of result of the test:
| Body weight before the test | Body weight during off-test | Tumor heavy (g) | Tumour inhibiting rate (%) | |
| control | 20.13± 1.21 | 21.94± 1.71 | 0.068 | |
| 10% tween group (technology two)+warm | 19.75± 0.91 | 21.39± 1.34 | 0.037 | 44.9 |
| 5% tween group (technology two)+warm | 18.79± 0.82 | 22.13± 0.96 | 0.040 | 41.2 |
| 2.5% tween group (technology two)+warm | 19.48± 0.76 | 21.58± 0.87 | 0.043 | 36.3 |
| 1.25% tween group (technology two)+warm | 19.57± 1.05 | 22.47± 0.34 | 0.047 | 30.3 |
| 0.625% tween group (technology two)+warm | 20.51± 1.35 | 22.12± 0.58 | 0.049 | 26..9 |
| Warm group | 20.08± 1.29 | 21.97± 1.63 | 0.049 | 27.9 |
| 10% tween group | 20.55± 1.06 | 21.79± 0.97 | 0.057 | 15.4 |
The 3rd batch of result of the test:
| Body weight before the test | Body weight during off-test | Tumor heavy (g) | Tumour inhibiting rate (%) | |
| control | 18.19± 1.05 | 20.73± 1.11 | 0.074 | |
| 10% tween group (technology two)+warm | 18.75± 0.81 | 22.72± 0.92 | 0.040 | 46.2 |
| 5% tween group (technology two)+warm | 19.27± 0.72 | 21.97± 1.44 | 0.043 | 42.5 |
| 2.5% tween group (technology two)+warm | 19.88± 1.19 | 22.47± 1.07 | 0.047 | 36.7 |
| 1.25% tween group (technology two)+warm | 19.91± 0.93 | 21.39± 1.33 | 0.050 | 32.5 |
| 0.625% tween group (technology two)+warm | 19.88± 1.21 | 22.59± 1.22 | 0.052 | 29.8 |
| Warm group | 18.39± 1.01 | 22.43± 0.89 | 0.0517 | 30.1 |
| 10% tween group | 19.77± 0.31 | 21.17± 1.27 | 0.0619 | 16.4 |
Inhibition test result among comparing embodiment 3 and the embodiment 4 is not difficult to find out; the claimed preparation-obtained sensitizer of technology three methods of the present invention to the suppression ratio of tumor apparently higher than undressed tween group and the sensitizer for preparing through technology two filter methods; and under the situation that obtains same therapeutic effect, the claimed needed effective dose of sensitizer of the present invention obviously reduces.
Embodiment 5: technology three preparations and technology two preparations are to the inhibitory action preliminary observation result (mtt assay) of growth of tumour cell:
SPC-A-1 human lung carcinoma cell line (OD value)
| Drug level | Matched group | Filter (preparation process two) | High pressure (preparation process three) | ||||
| 0.01％ | 0.05％ | 0.1％ | 0.01％ | 0.05％ | 0.1％ | ||
| X±s | 0.936 0.186 | 0.993 0.086 | 1.032 0.256 | 0.960 0.150 | 0.882 0.091 | 0.787 0.080 | 0.718 0.139 |
| Matched group | Filter (preparation process two) | High pressure (preparation process three) | |||||
| 0.01％ | 0.05％ | 0.1％ | 0.01％ | 0.05％ | 0.1％ | ||
| Suppression ratio (%) | 0 | 0 | 0 | 0 | 5.7 | 15.9 | 23.3 |
SGC-996 people's carcinoma of gallbladder cell (OD value)
| Drug level | Matched group | Filter (preparation process two) | High pressure (preparation process three) | ||||
| 0.05％ | 0.1％ | 0.15％ | 0.05％ | 0.1％ | 0.15％ | ||
| x±s | 0.512 0.045 | 0.462 0.050 | 0.418 0.049 | 0.377 0.051 | 0.395 0.053 | 0.387 0.050 | 0.376 0.053 |
| Matched group | Filter (preparation process two) | High pressure (preparation process three) | |||||
| 0.05％ | 0.1％ | 0.15％ | 0.05％ | 0.1％ | 0.15％ | ||
| Suppression ratio (%) | 0 | 9.76 | 18.4 | 26.4 | 22.8 | 24.4 | 26.6 |
Above-mentioned result of the test shows that the sensitizer that adopting process three prepares is under the relatively low situation of drug level, and its effect that suppresses tumor obviously is better than adopting process two preparation-obtained sensitizers.Therefore the claimed tween sensitizer of the present invention has good tumor killing effect.
The drug safety problem:
In addition, because with preparation process one (untreated Tween 80) prepared preparation less stable, so can not be used in the body, in vitro tests.
And conventional hemolytic test finds that technology two and technology three prepared preparation are comparatively safe in human body and animal experiment, and technology three obviously has potentiation than the effect of technology two.
Claims (8)
1. thermotherapy sensitizer, it is characterized in that: it is that Tween 80 stock solution adds the injection water or the injection normal saline solution is diluted to 10% concentration by getting, being heated to 70 ℃ stirred 20 minutes, cooling, filtration, embedding, heat sterilization, naturally cool to 70 ℃, vibrated 20 minutes, it is preparation-obtained to naturally cool to room temperature then.
2. thermotherapy sensitizer as claimed in claim 1 is characterized in that it can use under the situation of 2 times, 4 times, 8 times, 16 times of dilutions.
3. the application of thermotherapy sensitizer as claimed in claim 1 in the thermotherapy sensitizer of preparation treatment tumor.
4. application as claimed in claim 3 is characterized in that described sensitizer can strengthen the tumor killing effect of thermotherapy.
5. application as claimed in claim 3 is characterized in that it is 41 ℃ that described sensitizer can make the critical temperature of thermotherapy.
6. application as claimed in claim 3 is characterized in that the Tween 80 concentration in the sensitizer of effective dose can be 10% to 0.625%.
7. application as claimed in claim 3 is characterized in that described sensitizer can use under the situation of 2 times, 4 times, 8 times, 16 times of dilutions.
8. method for preparing the thermotherapy sensitizer, the steps include: to get Tween 80 stock solution adds injection water or injection normal saline solution and is diluted to 10% concentration, being heated to 70 ℃ stirred 20 minutes, cooling, filtration, embedding, sterilized 15 minutes for 121 ℃, naturally cool to 70 ℃ of vibrations 20 minutes, naturally cool to room temperature then.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101340049A CN101172113A (en) | 2007-10-26 | 2007-10-26 | Application of Tween 80 injection in substance base and thermotherapy for treating tumour |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101340049A CN101172113A (en) | 2007-10-26 | 2007-10-26 | Application of Tween 80 injection in substance base and thermotherapy for treating tumour |
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| Publication Number | Publication Date |
|---|---|
| CN101172113A true CN101172113A (en) | 2008-05-07 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2007101340049A Pending CN101172113A (en) | 2007-10-26 | 2007-10-26 | Application of Tween 80 injection in substance base and thermotherapy for treating tumour |
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| CN (1) | CN101172113A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106265923A (en) * | 2015-06-07 | 2017-01-04 | 浙江泰康药业集团有限公司 | A kind of method improving clarity of injection |
| CN110376092A (en) * | 2019-08-28 | 2019-10-25 | 西南医科大学 | A kind of compound haw thorn Content of Chlorogenic Acid and content of hesperidin measurement and integrated evaluating method |
-
2007
- 2007-10-26 CN CNA2007101340049A patent/CN101172113A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106265923A (en) * | 2015-06-07 | 2017-01-04 | 浙江泰康药业集团有限公司 | A kind of method improving clarity of injection |
| CN110376092A (en) * | 2019-08-28 | 2019-10-25 | 西南医科大学 | A kind of compound haw thorn Content of Chlorogenic Acid and content of hesperidin measurement and integrated evaluating method |
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