Background technology
1,3-Dihydroxyacetone, English name 1,3-dihydroxyaeetone or dihydroxyacetone, letter
DHA is written as, is simplest three carbon ketose, outward appearance is white or the crystallization of off-white powder shape, tool
There is sweet, cool taste, easy moisture absorption is simultaneously decomposed.It is the knot of dimer (1,4-Dioxane) under general state
Crystalline substance, can lentamente be dissolved in 1 part of water or in 15 parts of ethanol, be slightly soluble in ether, but through dissolving or adding
It is hot then be changed into monomer, the organic solvent such as monomer is soluble in water, ethanol, acetone and ether, fusing point is
It is 75~80 DEG C, water-soluble>250g·L-1(20 DEG C), when pH is 6.0, stabilization, is a kind of important change
Work, bio feedstocks, medicine, pesticide synthesis intermediate and polyfunctional food additive, purposes are very wide
It is general.
Dihydroxyacetone (DHA) plays the role of moisturizing, sun-proof and ultraviolet radiation preventing, can prevent moisture of skin
Excessive vaporization, can serve as the formula material of cosmetics, have special-effect especially as suncream.Two
Hydroxypropanone- is the intermediate product of glycometabolism, is played an important role during glycometabolism, with reduction
The effect of pig body fat, improves lean meat percentage.Supplement dihydroxyacetone (DHA) can improve organism metabolism rate and fat
Fat acid oxidase, can potentially active combustion fat and reduce body fat, thus with antiobesity action, and subtract
The incidence of disease of few relevant disease, it is also possible to caused by improving insulin sensitivity and reducing high cholesterol meals
Blood plasma cholesterol level, long-term supplement can make the blood sugar utilization rate increase and save Body development, to motion
Member can then improve aerobic endurance achievement.
Dihydroxyacetone (DHA) (DHA) is although purposes, is used extensively alone or in combination currently without on it
Report of the medicine in anti-tumor aspect effect.
Cis-platinum, the entitled cis diamino dichloro network platinum of chemistry belongs to cell cycle nonspecific agent (CCNSA), tool
There is cytotoxicity, the DNA replication dna process of cancer cell can be suppressed, and damage structure on its cell membrane,
There is stronger broad spectrum anticancer to act on.But its side effect is big, clinical manifestation is bone-marrow transplantation, leucocyte subtracts
Less, strong gastrointestinal reaction, n and V diarrhoea etc., irreversible Toxicity of Kidney and kidney failure,
Neurotoxicity, allergic reaction, electrolyte disturbance etc..Although cis-platinum has so strong toxicity,
It is still at present the fiest-tire medication of clinical treatment solid tumor due to its definite wide spectrum tumor-inhibiting action.
But clinic can not possibly heighten the effect of a treatment by increasing cis-platinum consumption simply, therefore set up the connection of cis-platinum
Close therapeutic regimen, tumor killing effect can be significantly increased in the case where its toxicity is not increased, be always swollen
The important topic of knurl medical research.
The content of the invention
In order to solve above-mentioned at least one technical problem, join the invention provides dihydroxyacetone (DHA) and cis-platinum
Share application of the medicine in anti-tumor aspect.
According to an aspect of the invention, there is provided a kind of antitumor medicine composition, its effectively into
Dividing includes dihydroxyacetone (DHA) and cis-platinum.
According to another aspect of the present invention, there is provided a kind of anti-tumor drug joint, is by dihydroxy
Acetone and cis-platinum are constituted.
One of according to the embodiment of the present invention, medication combined middle dihydroxyacetone (DHA) can be in oral formulations
Form, cis-platinum can be in injection form.
In accordance with a further aspect of the present invention, there is provided purposes of the dihydroxyacetone (DHA) in medicine is prepared, institute
Medicine is stated for antitumor, is that subject is administered simultaneously dihydroxyacetone (DHA) and cis-platinum.Administering mode can be with
According to its each conventional method of administration, consumption and the frequency.
According to the present invention, purposes of the combination of dihydroxyacetone (DHA) and cis-platinum in medicine is prepared is additionally provided,
The medicine is used for antitumor.
It is used for antineoplastic medicine box present invention also offers one kind, including dihydroxyacetone (DHA) and cis-platinum.
One of according to the embodiment of the present invention, dihydroxyacetone (DHA) and cis-platinum are arranged on difference in medicine box
Container in.
Another implementation method of the invention, dihydroxyacetone (DHA) is in oral dosage form, and cis-platinum is in note
Penetrate dosage form formula.
A kind of implementation method of the invention, the weight ratio of dihydroxyacetone (DHA) and cis-platinum is in medicine box
3375~4125:1.Preferably, the weight ratio of dihydroxyacetone (DHA) and cis-platinum is 3750:1.
It is described present invention also offers the purposes of the combination in medicine box is prepared of dihydroxyacetone (DHA) and cis-platinum
Medicine box is used for antitumor.
The solution have the advantages that proved by experiment:
1 test material
1.1 test samples
Title:Dihydroxyacetone (DHA) (DHA) solid powder
Unit is provided:There is provided by Suzhou Ya Bao medicament research and developments Co., Ltd
Positive control:Cisplatin for injection (Cisplatin), lot number:2WA2A1408055A, production
Producer:Qilu Pharmaceutical Co., Ltd., specification:20mg/ bottles
1.2 experimental animals
Kind, strain and grade:Balb/c-nude nude mouses, SPF grades
Source:Shanghai Ling Chang bio tech ltd
Credit number:SCXK (Shanghai) 2013-00185
Animal quality certification number:2013001812253
Body weight:16-18g (during arrival)
Sex:Male
2 testing programs
Nude mice by subcutaneous is inoculated with H460 cells (human large cell lung cancer cell line), treats that tumour is long to volume
100mm3During left and right, select that 36 gross tumor volumes are close, shape is preferably naked from 70 nude mices
Mouse, is divided into 6 groups, every group of 6 animals;
DHA groups:P.o., administered volume is 0.1mL/10g, bid, totally three weeks;
DHA+Cisplatin groups:Dihydroxyacetone (DHA) (DHA):P.o., administered volume is 0.1mL/10g,
bid;Cisplatin:4mg/kg, volume injected 0.1mL/10g, i.p, is administered once for every 5 days, and totally three
Week;
Cisplatin groups:4mg/kg, volume injected 0.1mL/10g, i.p, is administered once for every 5 days,
Totally three weeks;
Blank group:0.9% sodium chloride injection, administering mode is with DHA groups.
3 experimental techniques
3.1 inoculations
3.1.1 recover and expand H460 cells;
3.1.2 it is to be amplified to enough cells, cell is collected, matched somebody with somebody with 1640 culture mediums without serum
It is 2 × 10 into concentration7The cell suspension of cell/mL;
3.1.3 nude mice back right side subcutaneous vaccination, only, i.e., every nude inoculation cell number is 0.1mL/
2×106;
3.1.4 70 nude mices are inoculated with altogether, and knurl situation and tumor size are observed after inoculation.
3.2 packet administrations
3.2.1 treat that tumour is long to volume 100mm3During left and right, 36 tumours are selected from 70 nude mices
Volume is close, the preferable nude mice of shape, is divided into 6 groups, every group each 6.
3.2.2 it is grouped
With " 2 testing program "
3.3 medicines are prepared
DHA:Weigh solid powder 15.0g to be placed in 100mL volumetric flasks, use 5% glucose injection
Liquid is settled to graduation mark, is rocked to being completely dissolved in ultrasound.4 DEG C of refrigeration when being not used.
DHA+Cisplatin:Solid powder dihydroxyacetone (DHA) 15.0g is weighed to be placed in 100mL volumetric flasks,
Graduation mark is settled to 5% glucose injection, is rocked to being completely dissolved in ultrasound.Measure
0.6mg/mL cisplatin solutions 4.0mL adds 2.0mL physiological saline, is configured to 0.4mg/mL (4mg/kg)
Cisplatin solution, 4 DEG C of refrigeration when being not used.
All samples configuration in every three days is once.
3.4 measurements
From administration the 1st day, 3 gross tumor volumes and body weight were measured weekly.Put to death nude mice within 22nd day,
Take out tumour to weigh, take pictures, finally calculate tumour inhibiting rate.
3.5 evaluation indexes
Tumor volume change;The weight of animals changes;Last tumor weight.
4 Testing index and computational methods
4.1 gross tumor volumes (tumor volume, TV)
Computing formula is:TV=1/2 × a × b2, wherein a, b represent length and width respectively.
4.2 relative tumour volumes (relative tumor volume, RTV)
Computing formula is:RTV=TVt/TV1, wherein TV1(d during for sub-cage administration1) gross tumor volume,
TVtGross tumor volume during to measure each time.
4.3 Relative tumor proliferation rates T/C (%)
Computing formula is:
TRTV:Treatment group RTV;CRTV:Blank control group RTV.
4.4 knurl weight tumour inhibiting rates IR (%)
Computing formula is:
TTW:Treatment group's knurl weight;CTW:Blank control group knurl weight;TW(tumor weight):Tumour
Weight.
5 result of the tests
Concrete outcome is shown in Table 1, table 2 and Fig. 1, Fig. 2 and Fig. 3.
Table 1:Number of animals, body weight, gross tumor volume (TV), relative tumour volume (RTV), Relative tumor proliferation rate (T/C)
***P<0.01v.s.Blank(RTV)*:0.01<P<0.05v.s.Blank(RTV)
Table 2:Knurl weight and knurl weight tumour inhibiting rate
*:0.01<P<0.05v.s.Blank
6 discussion of results
6.1 tumour growth situations:Result shows that each group gross tumor volume has preferable dispersion, mark
, less than the 1/4 of mean, blank group tumour growth is good, the RTV=(1797.4 in test endpoint for quasi- deviation
±657.6)。
6.2 body weight:In whole process of the test, Cisplatin groups, DHA+Cisplatin, Body weight loss
Substantially, remaining each group increases normal.
6.3 Cisplatin groups:Clearly, performance body weight is decreased obviously toxic reaction, temperature decline,
Body weight loss about 16.7% in test endpoint, animal state is poor;Determine drug dosage schedule be every 5 days to
Medicine once, final administration number of times 4 times.Cisplatin tumor killing effects substantially (P=0.04), it is last its
T/C=60.3%, tumor-like hyperplasia is 44.6%.This also shows the test system reliability simultaneously, can use
In evaluating drug effect.
6.4 DHA groups:Non-toxic reaction, does not show obvious tumor-inhibiting action in this test model.
6.5 DHA+Cisplatin groups:Toxic reaction, performance Body weight loss, temperature decline,
Body weight loss about 15.7% during test endpoint, is numerically relatively used alone Cisplatin and has reduced.DHA
Administration 2 times daily, it is to be administered once for every 5 days that Cisplatin determines drug dosage schedule, final administration number of times 4
It is secondary.This group of tumor killing effect clearly (P=0.0059), last its T/C=44.9%, tumor-like hyperplasia
It is 53.3%.
6.6 brief summaries
In this experiment, DHA+Cisplatin groups are in human large cell lung cancer H460 cell transplantation knurls
Tumor killing effect is significantly stronger than Cisplatin groups on model, and will not increase the toxicity of chemical drug cis-platinum, it is believed that
DHA can play preferable tumor-inhibiting action with chemical drug Cisplatin.
The additional aspect of the present invention and advantage will be set forth in part in the description, partly will be from following
Description in become obvious, or by it is of the invention practice recognize.