CN108096258A - Cyclophosphamide and epirubicin combinational use and its detection device - Google Patents
Cyclophosphamide and epirubicin combinational use and its detection device Download PDFInfo
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- CN108096258A CN108096258A CN201810143187.9A CN201810143187A CN108096258A CN 108096258 A CN108096258 A CN 108096258A CN 201810143187 A CN201810143187 A CN 201810143187A CN 108096258 A CN108096258 A CN 108096258A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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Abstract
The present invention relates to medicine and pharmaceutical preparation research and development technology fields, and in particular to application of the cyclophosphamide with epirubicin drug combination in the drug for preparing treatment G. cephalantha.
Description
Technical field
The present invention relates to medicine and field of pharmaceutical preparations, specifically disclose cyclophosphamide and combine with epirubicin and are controlled in preparation
Treat the application in the drug of G. cephalantha.
Background technology
As many as the original site of head and neck neoplasm and histological type, occupy first of general tumour, wherein 90% is squamous cell
Cancer, there are about 650,000 neopathy people every year in the whole world.G. cephalantha (Squamous Cell Carcinoma of Head
And Neck, HNSCC) include laryngocarcinoma, carcinoma of mouth, nasopharyngeal carcinoma, hypopharyngeal cancer etc..Patient makes a definite diagnosis the treatment generally taken after HNSCC
Scheme is surgery excision and/or radiotherapy, for the small primary cancer (I phases or II phases) of no local transfer, can individually be adopted
It is treated with widened surgery excision or individual therapeutic radiation；The wider primary tumor of scope has regional lymph nodes
The case of (III phases or IV phases) is shifted, more uses preoperative or postoperative irradiation combination surgery excision therapeutic scheme.Although
Current treatment means are constantly improving, but the state of an illness for still having 2/3rds patients is not effectively controlled, Huan Zhewu
Year, operation or radiotherapy or chemotherapy cannot reach satisfactory therapeutic effect with knurl survival rate less than 50%.
Progress and the research that deepens continuously to HNSCC pathogenic mechanisms with medicine, also open the targeted therapy of HNSCC
New era.
Targeted therapy, refers to be identified using drug or other substances (such as monoclonal antibody) and to attack particular cancer thin
A kind of therapy of the born of the same parents without injuring normal cell, drug or other substances enter can specifically combine carcinogenic position in vivo
Point so that tumor cell specific is dead, and the normal tissue cell without involving near tumor cells, carcinogenic site can be
A genetic fragment in the protein molecular or tumour cell of inside tumor cells.
The drug for being presently used for clinical targeted therapy HNSCC is Cetuximab (Cetuximab) and Gendicine
(Gendicine).Cetuximab is human mouse chimeric monoclonal antibody, and mechanism of action is blocking epidermal growth factor
(Epidermal Growth Factor Receptor, EGFR) so that EGFR invaginates, so as to lose activation one system of downstream
The ability of row access is finally reached the purpose for the treatment of.Gendicine is that caused by tumor suppressor p 53 is delivered to tumour using adenovirus
The directed gene therapy drug of cell.
Whether Cetuximab or Gendicine, although patient can be treated to a certain extent, drug is to suffering from
The toxic side effect that person generates is also comparable apparent, such as vomiting, abdominal pain, white blood cell count(WBC) decline, have difficulty in breathing, dermal toxicity
Reaction, in some instances it may even be possible to severe allergic reaction, septicemia and renal failure etc. occur.Therefore, the secondary work of poison of target therapeutic agent is reduced
With improving the life quality of patient, the pain for reducing patient medication is to treat the elementary object of HNSCC.
Cyclophosphamide is a kind of common broad-spectrum anti-cancer drug, into human body after under the action of hepatomicrosome enzyme point
Solution releases the very strong chloroethyl phosphamide of alkanisation, so as to generate cytotoxicity to tumour cell.Epirubicin belongs to
Antibiotics tumour medicine, mechanism of action are that drug is directly embedded between the DNA core alkali pair of tumour cell, disturb transcription,
The formation of mRNA is prevented, inhibits the synthesis of DNA and RNA, so as to achieve the purpose that treatment.But in cyclophosphamide medication process
In, bone marrow suppression is most common toxic side effect, can also cause stomach damage and hepar damnification, and with medium to serious
Immunosupress；And epirubicin can generate cardiac toxic during single drug, cause myocardial damage, heart failure, and it is right
Liver causes to damage.
The content of the invention
The invention is intended to provide cyclophosphamide to combine answering in the drug for preparing treatment G. cephalantha with epirubicin
With.
In one embodiment, cyclophosphamide of the invention is combined with epirubicin is preparing the medicine for the treatment of G. cephalantha
Application in object.
In above application, the cyclophosphamide is combined with epirubicin, be in the form of compound medicament composition, it is described multiple
Square pharmaceutical combination includes cyclophosphamide and epirubicin.
In above application, the joint includes cyclophosphamide and is administered together simultaneously with epirubicin.
In above application, the cyclophosphamide is 0.67-1.5 with the united mass ratio of epirubicin:1.
In above application, the dosage form of the compound medicament composition can be oral tablet, capsule, parenteral solution
Deng.
Description of the drawings
Fig. 1 shows the influence figures that detection cyclophosphamide refers to mouse weight and internal organs with epirubicin drug combination；
Fig. 2 represents detection cyclophosphamide and influence figure of the epirubicin drug combination to mouse gastric tissue；
Fig. 3 is the structure diagram of detection device in embodiment three；
Fig. 4 is the structure diagram of Fig. 3 further grooves.
Specific embodiment
With reference to specific implementation, the present invention is described in further detail, but the embodiment is only used for understanding this hair
It is bright rather than limit the scope of the invention.
Reference numeral in Figure of description includes：Eyepiece 1, eye protection cylinder 2, slide plate 4, groove 5, spring 6, push away objective table 3
Plate 7.
Embodiment one
In the blood preparation of the court's acquisition HNSCC postoperative patients, gene is carried out through Shenzhen Hua Da gene limited company
Detection, compares the difference between cyclophosphamide independent medication and cyclophosphamide combined epirubicin medication, as a result such as Tables 1 and 2
It is shown.
The genetic test result of 1 cyclophosphamide of table
The genetic test result of 2 cyclophosphamide combined epirubicin of table
As shown in Table 1, when cyclophosphamide independent medication acts on detection gene, testing result prompting：Cyclophosphamide it is quick
Perception is higher or probability placed in the middle and higher or placed in the middle toxic side effect risk is up to 91.89%, and the sensibility of cyclophosphamide is higher
And the relatively low probability of its toxic side effect risk only accounts for 8.11%.When said gene testing result shows cyclophosphamide independent medication,
The ratio that the sensibility of cyclophosphamide is higher and its toxic side effect risk is relatively low is too low, secondary to the treatment poison of HNSCC postoperative patients
It is higher to act on risk, is unfavorable for the treatment to postoperative patient, is also unfavorable for improving the life quality of postoperative patient.
As shown in Table 2, during the medication of cyclophosphamide combined epirubicin, testing result prompting：The soft ratio of cyclophosphamide combined table
The probability that the sensibility of star is higher and its toxic side effect risk is relatively low is 97.30%, the sensitivity of cyclophosphamide combined epirubicin
The probability relatively low and that its toxic side effect risk is higher of property is only 2.70%.Sensibility during compared to cyclophosphamide independent medication compared with
For high and relatively low its toxic side effect risk probability is 8.11%, cyclophosphamide combined epirubicin medication significantly improves medicine
The sensibility of object, while it has been significantly reduced the toxic side effect risk of drug.
In conclusion comparison cyclophosphamide independent medication treatment HNSCC postoperative patients, cyclophosphamide combined epirubicin are used
When medicine treats HNSCC postoperative patients, can significantly improve the sensibility of drug significantly reduces the toxic side effect risk of drug simultaneously, has
Beneficial to the treatment of patient disease, be conducive to improve the life quality of patient, reduce the pain that patient is born over the course for the treatment of.
Embodiment two
In the blood preparation of the court's acquisition HNSCC postoperative patients, gene is carried out through Shenzhen Hua Da gene limited company
Detection evaluates drug according to Evidence grade and detects the correlation degree of gene, this correlation degree from pharmacogenetics and
Genome pharmacology data storehouse (The Pharmacogenetics＆Pharmacogenomics Knowledge Base,
PharmGKB).So-called PharmGKB is how one cause difference present in human individual's gene individual to drug response
The national research alliance that difference is studied, so-called Evidence grade are a set of evaluations of evidential matter that Oxford Evidence-Based Medicine Center proposes
System, for preventing, diagnosing, prognosis, the research evaluation in the fields such as treatment and harm research, the evaluation system is international and domestic
Doctor accepts extensively and uses.Wherein, refer to and repeat to study based on multinomial for 2A grades, medicine efficacy relation is probably meaningful；
2B grades refer to based on multinomial repetition research, but some researchs may be few without statistical significance or sample size；3 grades refer to and are based only upon 1
There is the research (not repeating) of significant difference or multinomial research but lack apparent drug effect relevance.
Testing result when cyclophosphamide independent medication acts on mthfr gene is as shown in table 3, cyclophosphamide and detection base
Because the correlation degree of MTHFR is 2A, show that cyclophosphamide and the medicine efficacy relation detected between gene M THFR may be meaningful,
But still have 16.22% the result shows that the toxic side effect risk of cyclophosphamide may be higher.
3 cyclophosphamide independent medication of table acts on testing result during mthfr gene
Testing result when cyclophosphamide independent medication acts on SOD2 genes is as shown in table 4, cyclophosphamide and detection base
Because the correlation degree of SOD2 is 2B, show cyclophosphamide and detect medicine efficacy relation between gene SOD2 may without statistical significance,
Therefore, although have 78.38% the result shows that cyclophosphamide is higher to the drug susceptibility of SOD2 genes, this result can
Can be without statistical significance, confidence level is relatively low.
4 cyclophosphamide independent medication of table acts on testing result during SOD2 genes
Testing result when cyclophosphamide independent medication acts on TP53 genes is as shown in table 5, as can be known from Table 5, ring phosphorus
The correlation degree of amide and detection gene TP53 is 2B, shows that cyclophosphamide and the medicine efficacy relation detected between gene TP53 may nothings
Statistical significance, therefore, the drug therapy sensibility of cyclophosphamide may the possible relatively low probability of higher and toxic side effect risk
It is 29.73% this result without statistical significance.
5 cyclophosphamide independent medication of table acts on testing result during CYP1B1 genes
Testing result when cyclophosphamide independent medication acts on CYP1B1 genes is as shown in table 6, as can be known from Table 6, ring
The correlation degree of phosphamide and detection gene C YP1B1 is 3, shows to lack between cyclophosphamide and detection gene C YP1B1 apparent
Drug effect relevance.
6 cyclophosphamide independent medication of table acts on testing result during CYP1B1 genes
Testing result when cyclophosphamide combined epirubicin medication acts on GSTP1 genes is as shown in table 7, from table 7
It understands, the correlation degree of the medication of cyclophosphamide combined epirubicin and detection gene GSTP1 is 2A, therefore cyclophosphamide combined table
It is soft probably more meaningful than the medicine efficacy relation between star medication and detection gene GSTP1, therefore, 97.30% result table
The drug susceptibility of bright cyclophosphamide combined epirubicin is strong and toxic side effect risk may relatively low this credible result degree height.
7 cyclophosphamide combined epirubicin medication of table acts on testing result during GSTP1 genes
In conclusion the correlation degree of cyclophosphamide and detection gene M THFR is 2A, medicine efficacy relation between the two may be
It is significant, but 16.22% the result shows that treated with cyclophosphamide pulse toxic side effect risk may be higher；Cyclophosphamide and detection
The correlation degree of gene SOD2 and TP53 be 2B, therefore the drug susceptibility of cyclophosphamide may it is higher may be without statistically significant
Property, it is with a low credibility；Cyclophosphamide lacks apparent drug effect relevance with detection gene C YP1B1.But cyclophosphamide combined table
The soft correlation degree than star and detection gene GSTP1 is 2A, and medicine efficacy relation is probably meaningful, therefore, has
97.3% testing result shows that the drug susceptibility of cyclophosphamide combined epirubicin medication is strong, and its toxic side effect risk can
This relatively low conclusion of energy is believable.
Therefore, during cyclophosphamide combined epirubicin medication treatment HNSCC postoperative patients, compared to exclusive use ring phosphinylidyne
Amine is treated, the former is capable of the sensibility of significantly increasing medicament and significantly reduces the toxic side effect risk of drug, is conducive to improve
HNSCC postoperative patients treat curative effect and life quality, reduce the pain that patient is born over the course for the treatment of.In addition, ring phosphinylidyne
Amine combines epirubicin medication and the medicine efficacy relation that detects between gene GSTP1 is likely to be meaningful, i.e. cyclophosphamide
The medication of joint epirubicin reaches the sensibility of significantly increasing medicament and significantly reduces medicine by acting on gene GSTP1
The purpose of the toxic side effect risk of object.
Three cyclophosphamide of embodiment is tested with epirubicin joint synergy
Cyclophosphamide can cause stomach damage and hepar damnification during independent medication, and with medium to serious
Immunosupress；And epirubicin can generate cardiac toxic during independent medication, cause myocardial damage, heart failure, and
Liver is caused to damage.Therefore, continuous 3 cycle medication (first day is established in the present embodiment：Epirubicin=25-30mg/kg*
70kg*0.0026 ÷ 20g=227.5-273mg/kg, 10mg/ bottle, therefore using 5mg/20g；First day：Cyclophosphamide=20-
40mg/kg*70kg*0.0026 ÷ 20g=166-332mg/kg, 200mg/ bottle, 5mg/20g；Interval 6 days) experimental animal mould
Type, the medication of verification cyclophosphamide combined epirubicin compare cyclophosphamide independent medication to internal organs such as heart, the livers of animal
Influence and the influence to Immune Function In Animals.Specific method is as follows：
(1) experimental animal
8 experimental animal of table
(2) experiment reagent and equipment
9 experiment reagent of table
(3) experimental facilities
10 experimental facilities of table
(4) preparation of reagents
A) PBS buffer solution is prepared
Table 11PBS buffer formulations
It is matched according to buffer solution shown in table 11, accurately weighs KCl, KH respectively2PO4、NaCl、Na2HPO4·12H2O
0.2072g, 0.2075g, 8.0073g, 2.9015g, with deionized water dissolving in beaker, after be transferred to the volumetric flask of 1000mL
In, deionized water constant volume shakes up, spare after high pressure sterilization.
B) preparation of reagent object storing solution is supplied
Cyclophosphamide and each 30mg of epirubicin (each) are weighed respectively, are matched somebody with somebody with the PBS buffer solution dissolving warmed after sterilizing
10mg/ml is made supplies reagent object storing solution, spare after 0.22 μm of filtering with microporous membrane.
(5) animal packet and administration
By several Balb/c mouse be randomly divided into physiological saline group (1.0ml), epirubicin group (0.5ml epirubicins+
0.5ml physiological saline), cyclophosphamide group (0.5ml cyclophosphamide+0.5ml physiological saline) and drug combination group (0.5ml ring phosphorus
Amide+0.5ml epirubicins) totally four groups of experimental groups, every group of each 3 mouse.It is administered mouse in a manner of being injected intraperitoneally, continuous 3 weeks
(first day) phase was administered, and raising totally 3 weeks, record weight, draws mouse weight variation diagram before being administered.
(6) separation of internal organs
After mouse is taken off neck execution, the 3min that sterilizes is placed in 75% alcohol；It is subsequently placed in super-clean bench, is cut off in left veutro
Osculum, exposure peritonaeum, finds spleen, heart, liver, stomach, is drawn off being soaked in PBS buffer solution respectively, cleaning surface knot
Tissue is formed, each organ surface liquid is blotted, weighs and record, calculate each organ index.Organ index calculation formula is：Internal organs weight
Measure the weight (g) of (mg) × 10/, unit mg/10g.
(7) stomach pathological examination
After stomach tissue is inserted the fixation of 10% formalin, using PBS buffer solution soaked overnight, conventional gradients ethyl alcohol takes off
4mm paraffin sections are made in water, paraffin embedding.After dimethylbenzene dewaxing and graded ethanol rehydration, Hematoxylin-eosin dyeing is carried out,
Graded ethanol dehydration is carried out again, cements out the ethyl alcohol in histotomy with dimethylbenzene after dehydration.Neutral gum is finally added dropwise
Mounting is observed under detection device as shown in Figure 3, takes pictures.
Detection device as shown in Figure 3 includes eyepiece 1 and objective table 3, and the upper end of eyepiece 1, which is fixedly connected, to be useful for blocking light
The eye protection cylinder 2 of line, the diameter of 2 upper end of eye protection cylinder are more than the diameter of eyepiece 1, and eye protection cylinder 2 is made of rubber material；Objective table 3 is slided
It is dynamic to be connected with slide plate 4, open up that there are five for placing the groove 5 of detection sample, with reference to shown in Fig. 4, the side of groove 5 on slide plate 4
Wall is fixedly connected with spring 6, and spring 6 is fixedly connected with push plate 7, and push plate 7 is fixedly connected with sponge close to the one side of detection sample
Protective layer.When specifically used, the spring 6 in compression pocket 5 so that spring 6 has elastic-restoring force, and detected sample is placed
In the groove 5 of slide plate 4, release spring 6, push plate 7 props up sample, and the sample in detection process is avoided to move.It detected
Cheng Zhong, sponge protective layer can effectively protect sample, avoid sample broke.Due to being opened up on slide plate 4, there are five groove 5, users
Can simultaneously five detected samples are placed on slide plate 4, detect sample when the replaceable next sample of sliding skateboard 4 into
Row detection, can not only so facilitate detection, moreover it is possible in the case of avoiding one sample of one-time detection, cause sample after repeated detection
Chaotic happens, and causes sample serious mistake not corresponding with data.It is further, since fixed on the eyepiece 1 of detection device
Eye protection cylinder 2 is connected with, therefore, user need not be shut out the light when using this equipment with hand, can attentively adjust objective table
Position, so as to clear view sample.Also, eye protection cylinder 2 is made of rubber material, and hardness is relatively low, has to user's eye and protects
Shield acts on.The diameter of 2 upper end of eye protection cylinder is more than the diameter of eyepiece 1, very convenient for the user to wear glasses, improves
User uses the comfort of this equipment.
(8) experimental result
A) variation of each group mouse weight and organ index
After the administration of each group mouse, different variations has occurred in weight, and the organ index of each group mouse also has significant difference,
As a result as shown in table 12 and Fig. 1.Except the weight of physiological saline group mouse shows growth, remaining each group mouse weight shows negative increasing
It is long, but the negative growth of drug combination group is slightly smaller than remaining two groups negative growth.The size sequence of each group mouse liver index is made a living
Manage brine group>Epirubicin group>Cyclophosphamide group>Drug combination group.Compared with physiological saline group, the liver of remaining each group mouse
Index is substantially reduced, this may be since cyclophosphamide and the medication simultaneously of both drugs of epirubicin or independent medication all can
The liver function of mouse is impacted, from data for, drug combination group the liver function of mouse is influenced it is even more serious,
So epirubicin commissural arch cyclophosphamide regimen can't mitigate damage of the drug to mouse liver function, but with ring phosphinylidyne
Amine independent medication compares, it is found that it is close the two influences the liver function of mouse.From index and spleen index as can be seen that drug combination pair
The splenic injury of mouse is less than cyclophosphamide independent medication, so, the medication of cyclophosphamide combined epirubicin can mitigate drug
Damage to mouse spleen, so as to mitigate harmful effect of the drug to immune function of mice.From the point of view of each group mouse heart index,
Toxic side effect of the cyclophosphamide to it is not embodied, conjecture is the non-body of heart of mouse since the dosage of cyclophosphamide is relatively low
Reveal apparent damage situations.
Changes of weight/organ index of 12 mouse of table
B) influence of each group drug to the paraffin section of mouse gastric injury
Drawn materials by the stomach tissue to mouse, make paraffin section, detection device shown in Fig. 3 (10 times and
40 times) under carry out photographic analysis.From fig. 2 it can be seen that the stomach tissue form of physiological saline group (A groups) is complete, stomach substrate
Layer, mucous membrane layer thickness are larger and complete, external villus marshalling, no lesion and damage；The gastric mucosa hair of epirubicin group (B groups)
Raw lesion tissue, there is more inflammatory cell infiltration in the most external of mucous layer；The mucosa tissue of cyclophosphamide group (C groups)
Lesion has occurred, there is more inflammatory cell infiltration, mucous membrane shallow-layer meronecrosis in mucous layer most external；Although drug combination group
The gastric mucosa surface of (D groups) has a small amount of inflammatory exudate, but situation is mitigated compared with B groups and C groups.From this, ring phosphinylidyne
Amine joint epirubicin medication can mitigate damage of the drug to mouse stomach tissue.
In conclusion compared to cyclophosphamide independent medication, the medication of cyclophosphamide combined epirubicin can mitigate drug
Influence to mouse weight.Although drug combination cannot mitigate toxic side effect of the drug to mouse liver function, it is subtracting
Light drug is to the influence in terms of mouse spleen function or has certain effectiveness, i.e., drug combination can mitigate drug to mouse
The toxic side effect of immune function.In addition, drug combination can also mitigate the toxic side effect that drug generates Mouse Stomach, in certain journey
Cyclophosphamide is repaired on degree to damage caused by the gastric mucosa of mouse.
Example IV cyclophosphamide and the mass ratio of epirubicin drug combination are tested
PBS buffer solutions and the preparation reference embodiment three for reagent object storing solution in the present embodiment.To draw ring phosphorus
The ratio of amide and epirubicin drug combination, in the present embodiment by G. cephalantha (late period) model mice of several purchases with
Machine is divided into first group (0.3ml cyclophosphamide+0.7ml epirubicins), second group of (soft ratio of 0.4ml cyclophosphamide+0.6ml tables
Star), the 3rd group (0.5ml cyclophosphamide+0.5ml epirubicins), the 4th group (0.6ml cyclophosphamide+0.4ml epirubicins),
5th group (0.7ml cyclophosphamide+0.3ml epirubicins), the 6th group (1.0ml cyclophosphamide), the 7th group of (the soft ratio of 1.0ml tables
Star) and the 8th group (1.0ml physiological saline) totally eight groups of experimental groups, every group of each three mouse.It is administered in a manner of being injected intraperitoneally, continuously
Administration raising in first day weekly, records each group mouse survival cycle, and calculates each group mouse Average Survival cycle.
As a result as shown in table 13, for the 8th group of mouse in the case of no drug therapy, the Average Survival cycle is 18.3 days,
The Average Survival cycle of 6th group of mouse and the 7th group of mouse is shorter than cyclophosphamide and the mouse of epirubicin drug combination group.
(cyclophosphamide is 3 with epirubicin medicine quality ratio to first group of mouse:7) time to live is 31.3 days, is drug combination group
In middle shortest one group of the Average Survival cycle, (cyclophosphamide is 7 with epirubicin medicine quality ratio to the 5th group of mouse:And first 3)
The Average Survival cycle of group mouse is very nearly the same.(cyclophosphamide is 1 with epirubicin medicine quality ratio to 3rd group of mouse:1)
The Average Survival cycle is 52.3 days, is longest one group of Average Survival cycle in drug combination group.4th group of mouse (cyclophosphamide
It is 6 with epirubicin medicine quality ratio:4) the Average Survival cycle is only second to the 3rd group of mouse, second group of mouse (cyclophosphamide
It is 4 with epirubicin medicine quality ratio:6) the Average Survival cycle occupies the 3rd.It can be seen that becoming of being presented of data in table 13
Gesture is：When the ratio of cyclophosphamide and epirubicin drug combination is closer to 1:1, the Average Survival cycle of mouse is longer.Therefore,
The ratio for showing cyclophosphamide and epirubicin drug combination is 1:When 1, poison that cyclophosphamide and epirubicin generate mouse
It is less side effects, the effect of cyclophosphamide and epirubicin drug combination more preferably.
The 13 each group mouse survival cycle of table
Claims (4)
1. application of the cyclophosphamide with epirubicin drug combination in the drug for preparing treatment G. cephalantha.
2. application as described in claim 1, the cyclophosphamide are combined with epirubicin, united form is to contain ring phosphinylidyne
The compound medicament composition of amine and epirubicin.
3. application as claimed in claim 2, the cyclophosphamide is 0.67-1.5 with the united mass ratio of epirubicin:1.
4. application as claimed in claim 3, the cyclophosphamide is 1 with the united mass ratio of epirubicin:1.
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| CN106727633A (en) * | 2016-12-20 | 2017-05-31 | 井冈山市红扁担科技有限公司 | A kind of composition and its application with treatment adenocarcinoma of lung effect |
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| CN106727633A (en) * | 2016-12-20 | 2017-05-31 | 井冈山市红扁担科技有限公司 | A kind of composition and its application with treatment adenocarcinoma of lung effect |
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| 刘泽源: "《常用药物使用须知及配伍禁忌》", 31 October 2008, 军事医学科学出版社 * |
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