CN1657100B - Nano-class preparation for selective target stomach cancer-and lymph system and its preparation method - Google Patents
Nano-class preparation for selective target stomach cancer-and lymph system and its preparation method Download PDFInfo
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Abstract
A nano-class medicine in the form of injection for treating stomach cancer and its transfer to lymph node is prepared from nano-class activated carbon, anticancer medicine effective to stomach cancer, and physiologic saline. Its features its selective target toward stomach cancer and lymph system.
Description
Technical field
The present invention relates to a kind of selectivity targeting gastric cancer and lymphoid nanoscale preparation and preparation method thereof.Said preparation comprises nano level absorbent charcoal carrier and anti-gastric cancer medicine, belongs to a kind of new targeting preparation that is used for curing gastric cancer.
Background technology
The radical treatment of gastric cancer is an excision at present.Prevention of postoperative recurrence and the major measure that shifts are chemotherapy.But operative therapy can not thoroughly solve the transfer and the recurrence of gastric cancer, and the cancerous cell that is caused in art plantation is shifted also of common occurrence.Chemotherapy is the main supplementary means that recurs and shift behind inoperable late gastric cancer and the prevention radical operation for carcinoma of stomach.For chemotherapy, be not to be at present because cancer therapy drug can not kill cancer cell, but because chemotherapeutics lacks the selectivity to cancerous cell, it is the most responsive to the cancer therapy drug in the circulation also to kill normal cell, especially medulla hematopoietic system in kill cancer cell.Cause the reason of chemotherapy failure, body can not tolerate drug toxicity and the drug withdrawal of having to often.Therefore, find the medicine of selectively killing cancerous cell or make medicine can optionally act on cancerous tissue or cancerous cell, reduce the amount that enters body circulation medicine, reduce it to normal structure and cells injury effect, can effectively treat cancer, avoid or reduce postoperative recurrence and transfer, improve patient's no tumor life cycle or cancer is thoroughly treated.
With active carbon as carrier absorption anticarcinogen carry out intraperitoneal chemotherapy and lymphatic chemotherapy be rose in recent years be directed to stomach cancer metastasis and recurrence and the chemotherapy means of a kind of high selectivity of taking, high concentration, super-strengthening.Its ultimate principle is that the lymphoid tissue tropism of active carbon reaches the slow release characteristic to the absorption anticarcinogen.The activated carbon adsorption anticarcinogen has changed the dosage form of anticarcinogen, compares with conventional anticarcinogen aqueous solution, has 5 outstanding characteristics: (1) high adsorption and functional slow-release; (2) lymphoid tissue tropism; (3) local anelasticity; (4) tack of tumor surface; (5) toxic and side effects is little.Because the high adsorption of active carbon, thereby can adsorb a large amount of anticarcinogens.The particle diameter of micro activated carbon particle is bigger, can enter lymphatic vessel and can not be absorbed by blood vessel.After being injected in abdominal cavity, tumor by local zone or its draining lymph node, just can only dividing a word with a hyphen at the end of a line, and in lymph node, assemble, thereby have very high lymphoid tissue tropism, and in lymphsystem, retain for a long time along lymphsystem.Because the anticancer dose of its absorption is big, has functional slow-release again, thereby can make around it anticarcinogen long term maintenance in high concentration, kill transfer cancer and free cancer cell in the lymphsystem, play and kill the small cancer that operation can not remove and the effect of cancerous cell (the clinical chemical scavenging that is referred to as), therefore can prevent the recurrence of cancer effectively.Simultaneously because its long-term existence on the only way which must be passed of cancerometastasis, therefore can be blocked the transfer of cancer effectively.The active carbon of the absorption anticarcinogen of long-term existence in cancer district lymphoid tissue can also be brought into play direct lethal effect to cancerous tissue.Because active carbon can be attached to the cancerous cell surface, discharge anticarcinogen on the surface of cancerous cell, thereby be more conducive to the performance of cancer therapy drug effect.Because can not absorbing by blood vessel, active carbon enters blood circulation; thereby anticarcinogen also seldom or can not enter blood circulation; therefore can or seldom other normal or sensitive organization such as blood system, bone marrow not caused damage, reduce the toxicity, side effect of anticarcinogen effectively.
When addressing the activated carbon adsorption anticarcinogen gastric cancer carried out many superioritys of intraperitoneal chemotherapy and lymphatic chemotherapy, be also noted that in the clinical practice that active carbon also exists some problems when being used for intraperitoneal chemotherapy, the application of restriction intraperitoneal chemotherapy and lymphatic chemotherapy. the one, the particle diameter of at present used active carbon is bigger, be micron order, as enter blood circulation, the danger that causes thromboembolism is arranged; The 2nd, at present used micro activated carbon particle form is irregular, stimulates local organization easily, causes inflammation, and causes abdominal adhesions; The 3rd, be not used in the special preparation of gastric cancer intraperitoneal chemotherapy and lymphatic chemotherapy at present, clinician oneself mixes the back in when operation with active carbon and uses with anticarcinogen often. and therefore not only use is inconvenient, and preparation process is nonstandard, adsorbance is irregular, and causing infection easily. above content is referring to Jansen M etc., Effects of intraperitonealmitomycin C adsorbed on activated carbon on adhesion formationand mesothelial cells in vitro, Eur.J.Surg., 2000,166,572-6.
The invention summary
The inventor is by discovering, active carbon is made nano level active charcoal granule, then resulting nano level active charcoal granule and the combination of known anticarcinogen are made the nanoscale preparation, can make anticarcinogen selectivity targeting stomach organization and lymphsystem, simultaneously can not cause thromboembolism and abdominal adhesions, thereby solve above-mentioned defective of the prior art.
Therefore, one aspect of the present invention provides a kind of selectivity targeting gastric cancer and lymphoid nanoscale preparation, and said preparation comprises nano level active charcoal and anticarcinogen.
Another aspect of the present invention provides a kind of method for preparing selectivity targeting gastric cancer and lymphoid nanoscale preparation, and this method may further comprise the steps:
Anticarcinogen is made aqueous solution;
The nano level active charcoal is placed the anticarcinogen aqueous solution, adsorb under certain condition;
After absorption finishes, remove moisture, obtain nano level active charcoal-anticarcinogen;
Nano level active charcoal-anticarcinogen is carried out packing, sealing, sterilizes, keeps in Dark Place.
Detailed Description Of The Invention
As mentioned above, one aspect of the present invention provides a kind of selectivity targeting gastric cancer and lymphoid nanoscale preparation, and said preparation comprises nano level active charcoal and anticarcinogen.
In nanoscale preparation of the present invention, the nano level active charcoal can be by using the preparation of commercially available active carbon of ball mill ball milling or commercially available medical activated carbon.In the nano level active charcoal of gained, preferable particle size is that the activated carbon particles of 10-800nm accounts for more than 95% of total number of particles, and preferably its mean diameter is 299 ± 150nm.
In nanoscale preparation of the present invention, anticarcinogen can be the anti-gastric cancer medicine of using always, for example ametycin and 5-fluorouracil etc., preferably ametycin.
In nanoscale preparation of the present invention, nano level active charcoal and anticarcinogen can be 4 as the weight ratio of ametycin: 1-18: 1, be preferably 8.5: 1.
Nanoscale preparation of the present invention can also comprise other pharmaceutically acceptable dispersion stabilizer, for example tween 80, dextran, fabaceous lecithin, sodium deoxycholate etc.
Another aspect of the present invention provides a kind of method for preparing selectivity targeting gastric cancer and lymphoid nanoscale preparation, and this method may further comprise the steps:
Anticarcinogen is made aqueous solution;
The nano level active charcoal is placed the anticarcinogen aqueous solution, adsorb under certain condition;
After absorption finishes, remove moisture, obtain nano level active charcoal-anticarcinogen;
Nano level active charcoal-anticarcinogen is carried out packing, sealing, sterilizes, keeps in Dark Place.
In a preferred embodiment of above-mentioned preparation method, nano level active charcoal and anticarcinogen can be 4 as the weight ratio of ametycin: 1-18: 1, be preferably 8.5: 1.
In another preferred embodiment of above-mentioned preparation method, can use distilled water that anticarcinogen is made aqueous solution.Wherein, distilled water and anticarcinogen can be 6 as the weight of ametycin: 1-25: 1, be preferably 12.5: 1.
In another preferred embodiment of above-mentioned preparation method, can under the sonic oscillation condition, carry out adsorption operations.Wherein adsorption time can be 20-60 minute, is preferably 30 minutes.
In another preferred embodiment of above-mentioned preparation method, can use conventional method to remove moisture, preferably use freezing hypobaric drying method to remove moisture.
In another preferred embodiment of above-mentioned preparation method, can use glass ampoule to carry out packing.The content of the middle nano level active charcoal of each glass ampoule (10ml) can be 0.85-3.4g after the packing, is preferably 1.7g; And the content of anti-gastric cancer medicine can be 0.1-0.4g in each glass ampoule (10ml), is preferably 0.2g.
Nanoscale preparation of the present invention is mainly used in gastric cancer intraperitoneal chemotherapy and lymphatic chemotherapy, with recurrence and the transfer that prevents gastric cancer; Also can be used for before the radical correction or art in labelling lymph node and kill wherein small transfer cancer, play simultaneously and instruct operation to remove and the effect of chemical scavenging, to prevent the recurrence and the transfer of gastric cancer; Also can be used for the treatment of gastric cancer peritonitis and gastric cancer ascites.
During use, with normal saline dilution do under the stomach serous coat, lymph node, cancer district, cancerous tissue injection or lumbar injection, be used for cancerous peritonitis and cancer ascites that gastric cancer intraperitoneal chemotherapy and lymphatic chemotherapy, gastric cancer cause; Also can be used for cancer operation tense marker lymph node, instruct " chemical scavenging " of operation removing or metastatic lymph node.
Selectivity targeting gastric cancer of the present invention and lymphoid nanoscale preparation have following new characteristics:
1,,,, can not cause thromboembolism even therefore nanoscale preparation of the present invention enters circulation much smaller than the blood capillary diameter because the carrier particle particle diameter is a nanoscale yet;
2, because when preparation nano level active charcoal of the present invention, ball mill grinds for a long time to active carbon, it is subsphaeroidal that it is become in form, and it is level and smooth that the surface becomes, therefore nanoscale preparation of the present invention zest to peritoneum behind lumbar injection reduces, so less causing inflammation, thereby also seldom or not cause peritoneal adhesion;
3, because the preparation process of nanoscale preparation of the present invention is unified, and adsorption time is constant, therefore the ratio rule of active carbon and anticarcinogen makes the use of dosage more regular, thereby can receive better therapeutic;
4, the nanoscale preparation of the present invention of special preparation can be prepared when having avoided clinical practice through conventional sterilization treatment temporarily, is easy to cause the disadvantage of infection owing to the sterilized process;
5, prepare nanoscale preparation of the present invention, saved the trouble of interim absorption preparation, the convenient application.This nanoscale preparation not only can use in the senior hospital with surgical condition, also can use in the rural area that does not have surgical condition;
6, used nano level active charcoal has the ability of stronger absorption anticarcinogen than present used micron order active carbon, can make intraperitoneal or the in-house active drug concentration of injection site keep the longer time after abdominal cavity or lymph node injection;
7, the toxicity of nano level active charcoal itself reduces than the micron order active carbon, has better safety coefficient during use;
8, in experimental intraperitoneal chemotherapy, the nano level active charcoal has better therapeutic than the micron order active carbon, and cancer suppressing ratio can reach more than 85%;
9, the anticarcinogen in the nanoscale preparation of the present invention preferably adopts ametycin.The dose-effect relationship of killing stomach cancer cell of ametycin is index, therefore improve its concentration in cancerous tissue, abdominal cavity and lymphsystem with this nanoscale preparation after, obviously improve the therapeutic effect of gastric cancer and can reduce recurrence effectively and transfer.
The specific embodiment
Below in conjunction with practical application, the preparation method and the application of selectivity targeting gastric cancer of the present invention and lymphoid nanoscale preparation is further described.These examples only are used to illustrate the present invention, and do not play the qualification effect.
Embodiment 1: the preparation of nano level active charcoal
Get the about 40g of commercially available medical activated carbon (Beijing is Fine Chemical Works energetically), pack into planet board ball mill ball milling 60 hours. the active carbon 3g that gets then behind the ball milling adds the abundant mixing of water 3000ml after the distillation three times, left standstill 72 hours, treat in the visible obvious sediment of container bottom, its supernatant liquid is transparent, when precipitation and supernatant boundary are clearly demarcated, getting supernatant puts in the 1000ml rustless steel filter, microporous filter membrane pressurization elimination moisture by 0.22 μ m, in baking oven, toasted 2 hours in 120 ℃. the water dilution after three distillations of last reuse, detecting and carry out grain size analysis with atomic force microscope. raw material 40g medical activated carbon can reuse, remove loss, the output of last gained nano level active charcoal is 38g.
Embodiment 2: the preparation of nanoscale preparation of the present invention
Get the anticarcinogen ametycin 12g that nano level active charcoal 102g and Japan consonance Pharmaceutical Co., Ltd according to the preparation of the method for embodiment 1 produce;
With ametycin be dissolved in that 150ml is aseptic, in the apyrogeneity distilled water;
The nano level active charcoal is placed mitomycin c solution, and absorption is 30 minutes under the sonic oscillation condition;
Remove moisture with freezing hypobaric drying method, get solid drying thing 114g;
Nano level active charcoal-ametycin of 114g is sub-packed in 60 10ml glass ampoules, and every bottle contains nano level active charcoal and ametycin and respectively is 1.7g and 0.2g; Also 114g nano level active charcoal-ametycin can be sub-packed in the glass ampoule of 120 10ml, every bottle contains nano level active charcoal 0.85g, ametycin 0.1g; Also nano level active charcoal-ametycin of 114g can be sub-packed in the glass ampoule of 30 10ml, every bottle contains nano level active charcoal-ametycin 3.8g, and wherein the content of nano level active charcoal and ametycin respectively is 3.4g and 0.4g;
Glass ampoule is sealed;
Autoclave sterilization 120 minutes keeps in Dark Place.
By above preparation method, obtain the nanoscale preparation of following different size: 1) nano level active charcoal 1.7g+ ametycin 0.2g/10mL glass ampoule; 2) nano level active charcoal 0.85g+ ametycin 0.1g/10mL glass ampoule; 3) nano level active charcoal 3.4g+ ametycin 0.4g/10mL glass ampoule.
Embodiment 3: the biological activity test of nanoscale preparation of the present invention
Except the administration time difference, the remainder of method of testing is referring to Liang Han etc., the clinical and experimental study of activated carbon adsorption ametycin intraperitoneal chemotherapy, Chinese clinical tumor, 2000,27,897-901; Li Yishengs etc., lymphatic chemotherapy is to the clinical treatment research of gastric cancer lymph metastasis kitchen range, Chinese clinical tumor, 2001,28,771-774.
The nanoscale preparation of getting embodiment 2 preparations has carried out experimental intraperitoneal chemotherapy to nude mice people gastric cancer peritoneal metastasis model.The result shows that the cancer that this nanoscale preparation shifts plantation has tangible killing action, and curative effect obviously is better than free ametycin intraperitoneal chemotherapy and with micron order activated carbon adsorption ametycin intraperitoneal chemotherapy, the results are shown in Table 1.
Table 1. nanoscale preparation of the present invention is to the intraperitoneal chemotherapy effect of people's gastric cancer nude mice abdominal cavity plantation membranous type
| Handle | Tumor heavy (g) | Tumour inhibiting rate (%) |
| Normal saline 20ml/kg ip | 0.222±0.180 | - |
| Micron order active carbon-ametycin 38.25mg/kg (containing active carbon 33.75mg/kg, ametycin 4.5mg/kg) ip | 0.069±0.054 ＊ | 68.92 |
| Free ametycin 4.5mg/kgip | 0.084±0.053 | 62.16 |
| Handle | Tumor heavy (g) | Tumour inhibiting rate (%) |
| Nano level active charcoal-ametycin 19mg/kg (containing active carbon 17mg/kg, ametycin 2mg/kg) ip | 0.033±0.021 ＊# | 85.14 |
| Nano level active charcoal-ametycin 6.3mg/kg (containing active carbon 5.6mg/kg, ametycin 0.7mg/kg) ip | 0.092±0.083 | 58.56 |
| Nano level active charcoal-ametycin 2.2mg/kg (containing active carbon 1.97mg, ametycin 0.23mg/kg) ip | 0.116±0.107 | 47.75 |
Mean±SD，n＝8。
*Compare with the normal saline group p＜0.05; Compare with free mitomycin C group #p＜0.05.The BALB/C-nu nude mice, 4 ages in week, body weight 12-15g, (inoculation back, 1.3 * 10-6) abdominal cavities beginning in the 12 day administration of people's gastric cancer nude mice transplantation model cell suspension, put to death in the 22 day after administration, anatomic observation tumor growth situation is got tumor and is weighed on ten thousand/balance, carry out date processing with the SPSS11.0 statistical software, one factor analysis of variance test set differences.
The administration early of this preparation obviously reduces the transfer scope of abdominal cavity plantation gastric cancer and shifts the number of cancer, on part nude mice gastric cancer abdominal cavity implant cast, can avoid the generation and the transfer of gastric cancer fully, the results are shown in Table 2, table 3.
Table 2. nanoscale preparation of the present invention is to the metastasis and the anti-recurrence effect of plantation gastric cancer
| Handle | Average tumor heavy (mg) | The heavy suppression ratio (%) of tumor |
| Normal saline 0.2ml/10g ip | 60.2±36.3 | - |
| Ametycin 6mg/kg ip | 23.1±11.3 ＊ | 61.6 |
| Ametycin 0.36mg/kg ip | 24.2±9.5 ＊ | 59.8 |
| Ametycin-nano level active charcoal 51mg (containing ametycin 6mg, nano level active charcoal 45mg)/kgip | 19.1±9.7 ＊ | 68.3 |
| Ametycin-nano level active charcoal 153.9mg (containing ametycin 18mg, nano level active charcoal 135.9mg)/kg ip | 5.8±5.5 ＊＊## | 90.4 |
| Ametycin-nano level active charcoal 51.3mg (containing ametycin 6mg, nano level active charcoal 45.3mg)/kg ip | 12.5±8.0 ＊＊# | 79.2 |
| Handle | Average tumor heavy (mg) | The heavy suppression ratio (%) of tumor |
| Ametycin-nano level active charcoal 17.1mg (containing ametycin 2mg, nano level active charcoal 15.1mg)/kg ip | 22.3±8.1 ＊ | 63.0 |
Mean±SD，n＝8。
*P＜0.05,
*Compare with the normal saline group p＜0.01; #p＜0.05, compare with ametycin 6mg/kg group ##p＜0.01.56 of BALB/C-nu nude mices, in 6 ages in week, body weight 16g-20g divides 7 groups at random, and 8 every group, male and female half and half.Abdominal cavity inoculation people gastric cancer nude mice transplantation model cell suspension (1.6 * 10
6), inoculate administration after 1 hour, the 28th day anatomic observation got tumor and weighed after the administration.
Table 3. nanoscale preparation of the present invention is to the influence of tumour spread and growing state
Use the SPSS10.0 statistical package, contingency table analysis (Crosstabs), the χ of layering data
2Check shows: 2,3,4,5,6,7 groups and 1 group (normal saline matched group) ratio, P all＜0.01, show after oncocyte abdominal cavity inoculation intraperitoneal injection of drugs immediately, injection and this preparation all have the effect of obvious inhibition tumour spread behind simple MMC, active carbon and the MMC mixing.4,5,6 groups with 2 groups of ratios, P is all＜0.01; 6 groups with 3 groups of ratios, P＜0.05 show because absorption MMC active carbon has functional slow-release, so its tumor killing effect is better than simple MMC.6 groups with 4 groups of ratios, P＞0.05 shows under the MMC dosage same case, this preparation has and the same good inhibition tumour spread of bibliographical information activated carbon adsorption MMC and the effect of tumor growth.Compare p＜0.05 with 4 groups for 5 groups, show the active carbon nanorize after, further escalated dose obtains more tangible anti-recurrence transfer effect.6 groups with 5 groups of ratios, P＞0.05; 7 groups with 5 groups of ratios, P＞0.01; 7 groups with 6 groups of ratios, P＞0.05 shows that the active anticancer of preparation has certain dose-effect relationship.Can also see that from table the 5th group of 8 animals have four not have tumor to take place, all 8 mices all do not have the transfer cancer at the outer position of intestinal wall, show good metastasis effect.First group: the normal saline contrast; Second group: ametycin 6mg/kg ip; The 3rd group: ametycin 0.36mg/kg ip; The 4th group: ametycin-active carbon 51mg (containing ametycin 6mg, nano level active charcoal 45mg)/kg ip; The 5th group: ametycin-nano level active charcoal 153.9mg (containing ametycin 18mg, nano level active charcoal 135.9mg)/kg ip; The 6th group: ametycin-nano level active charcoal 51.3mg (containing ametycin 6mg, nano level active charcoal 45.3mg)/kgip; The 8th group: ametycin-nano level active charcoal 17.1mg (containing ametycin 2mg, nano level active charcoal 15.1mg)/kg ip.56 of BALB/C-nu nude mices, in 6 ages in week, body weight 16g-20g divides 7 groups at random, and 8 every group, male and female half and half.Abdominal cavity inoculation people gastric cancer nude mice transplantation model cell suspension (1.6 * 10
6), inoculate administration after 1 hour, the 28th day anatomic observation got tumor and weighed after the administration.
This nanoscale preparation can alleviate the toxic and side effects of ametycin effectively in performance good anti-stomach cancer metastasis and recurrence.Under 2.8 times the situation of dosage for free ametycin fatal dose, the hemopoietic function of bone marrow of nude mice is not still had obvious influence, and have only 1/3 free ametycin of this dosage obviously to suppress the hemopoietic function of nude mice bone marrow, the results are shown in Table 4.
Table 4. nanoscale preparation of the present invention is to the influence (hematological examination) of hemopoietic function of bone marrow: each organizes erythrocyte (RBC), leukocyte (WBC), platelet (PLT) measured value
| Group | RBC(10 12/L) | WBC(10 9/L) | PLT(10 9/L) |
| 1 | 8.46±0.27 | 4.08±1.64 | 810.13±93.03 |
| 2 | 8.32±0.62 | 4.62±2.01 | 654.63±134.72 ＊ |
| 3 | 8.69±1.23 | 4.28±1.57 | 775.13±161.31 |
| 4 | 8.49±0.39 | 4.21±1.38 | 832.50±136.10 |
| 5 | 8.55±0.32 | 4.10±0.89 | 761.00±94.66 |
| 6 | 8.38±0.55 | 5.06±2.40 | 832.38±154.50 |
| 7 | 8.53±0.90 | 4.30±2.35 | 807.50±108.04 |
Data are expressed as x ± s, row t check.Compare with 1 group (normal saline group),
*P＜0.05
The toxic and side effects of MMC mainly is bone marrow depression, descends the most remarkable with platelet.4 all hematological examinations after the administration, visible MMC high dose group is compared platelet with matched group and is significantly reduced, and prompting has bone marrow depression.Other groups are compared with matched group does not have significantly difference.Hematological examination shows that Application of Brand Active Carbon has significantly reduced the toxic and side effects of MMC, and this preparation is not seen obvious toxic-side effects yet under the situation of widely applying (the MMC 18mg/kg that tires is equivalent to 2 times of simple MMC median lethal dose(LD 50)).Tumor planting and grouping are with table 3.
After free 1 week of mitomycin C group nude mice medication, hair is matt, and activity obviously reduces, and body weight does not increase and decreases.And nano level active charcoal-mitomycin C group reaches at ametycin dosage under the situation of 2.8 times of lethal doses, still Non Apparent Abnormality performance of animal, only after 1 week of medication, the increase of body weight has slightly and slows down, but 4 week the back compare no significant difference with matched group, the results are shown in Table 5.
The influence that table 5. nanoscale preparation of the present invention increases the weight of animals
n＝8。Compare with 1 group (normal saline group),
*P＜0.05,
*The SPSS10.0 statistical package is used in P＜0.01, according to the DATA DISTRIBUTION characteristics, adopts non parametric tests Mann-Whitney methods analyst, and weight gain value is represented with median (minima, maximum).Obviously become thin behind 2 groups of (MMC high dose group) animals administers, weighed in 1 week after the administration except that 1 body weight gain, before all the other 7 body weight are lower than medication, movable simultaneously the minimizing, hair is matt; 3 groups (MMC low dose group) and 5 groups of (MMC-nCH high dose group, MMC dosage 18mg/kg) animal 1 all weight gain values are lower than 1 group of (normal saline matched group) (P＜0.05).4 weeks after the administration are though 2 treated animal weight gain values are lower than matched group, not statistically significant.Other groups are compared with matched group does not have marked difference yet.56 of BALB/C-nu nude mices, in 6 ages in week, body weight 16g-20g divides 7 groups at random, and 8 every group, male and female half and half.Abdominal cavity inoculation people gastric cancer nude mice transplantation model cell suspension (1.6 * 10
6), inoculate administration after 1 hour.Grouping sees Table 3.
Conclusion
These results show that nanoscale preparation of the present invention has also obviously reduced the toxic and side effects of anticarcinogen in performance good anti-stomach cancer metastasis and recurrence effect.
By foregoing description, the present invention is disclosed comprehensively, those skilled in the art it should be understood that under the condition that does not depart from the spirit and scope of the invention, can implement the present invention in desired wide parameter area.
Claims (10)
1. selectivity targeting gastric cancer and lymphoid nanoscale preparation, comprise nano level active charcoal and anti-gastric cancer medicine, wherein the nano level active carbon granule directly accounts for more than 95% of total number of particles for the particle of 10-800nm, mean diameter is 299 ± 150nm, and wherein the weight ratio of nano level active charcoal and anti-gastric cancer medicine is 8.5: 1.
2. the nanoscale preparation of claim 1, wherein anti-gastric cancer medicine is an ametycin.
3. the nanoscale preparation of claim 1, wherein anti-gastric cancer medicine is a 5-fluorouracil.
4. the preparation method of the nanoscale preparation of claim 1, this method may further comprise the steps:
To resist the gastric cancer medicine to make aqueous solution;
The nano level active charcoal is placed anti-gastric cancer drug solns, adsorbed under the sonic oscillation condition 20-60 minute, wherein the weight ratio of nano level active charcoal and anti-gastric cancer medicine is 8.5: 1;
After absorption finishes, remove moisture, obtain nano level active charcoal-anti-gastric cancer medicine; With
Nano level active charcoal-anti-gastric cancer medicine is carried out packing, sealing, sterilizes, keeps in Dark Place.
5. the method for claim 4, anti-gastric cancer medicine wherein is an ametycin.
6. claim 4 or 5 method, wherein the weight ratio of water and anti-gastric cancer medicine is 6-25: 1.
7. the method for claim 6, wherein the weight ratio of water and anti-gastric cancer medicine is 12.5: 1.
8. claim 4 or 5 method, the time of wherein adsorbing is 30 minutes.
9. claim 4 or 5 method wherein contain nano level active charcoal 0.85-3.4g, and contain anti-gastric cancer medicine 0.1-0.4g in every 10ml glass ampoule in every 10ml glass ampoule after the packing.
10. the method for claim 9 wherein contains nano level active charcoal 1.7g, and contains anti-gastric cancer medicine 0.2g in every 10ml glass ampoule in every 10ml glass ampoule after the packing.
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Non-Patent Citations (4)
| Title |
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| 孙岚等.小鼠腹腔注射纳米活性炭体内去向追踪观察.中国药理学与毒理学杂志17 4.2003,17(4),第316页左栏. |
| 孙岚等.小鼠腹腔注射纳米活性炭体内去向追踪观察.中国药理学与毒理学杂志17 4.2003,17(4),第316页左栏. * |
| 曲秋莲等.纳米活性炭毒性及对丝裂霉素吸附性能研究.中国药理学与毒理学杂志17 4.2003,17(4),第314页右栏. |
| 曲秋莲等.纳米活性炭毒性及对丝裂霉素吸附性能研究.中国药理学与毒理学杂志17 4.2003,17(4),第314页右栏. * |
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