CN104998277B - A kind of resisting toxoplasmosis prescription medicine and its screening technique - Google Patents
A kind of resisting toxoplasmosis prescription medicine and its screening technique Download PDFInfo
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Abstract
The invention discloses a kind of resisting toxoplasmosis prescription medicine and its screening techniques, belong to field of medicaments.The present invention is by establishing mouse experiment toxoplasmosis animal model, choose ten kinds of sulfadiazine sodium injection, the side's Fu Sulfamethoxazole, lincomycin hydrochloride injection, Sulfamonomethoxime Sodium injection, Archie fluorine injection, acetyl spiramycin, pyrimethamine, roxithromycin, sweet wormwood, kuh-seng drugs, filter out two best prescriptions of resisting toxoplasmosis effect, respectively daimeton+pyrimethamine+TMP and the side's Fu Sulfamethoxazole+acetyl spiramycin.Mouse model and pig animal model are established, it is effective to demonstrate above-mentioned two prescription therapeutic artificial challenge's toxplasmosis in pigs, consistent with the therapeutic effect of mouse model.It is a kind of feasible method that this research, which was demonstrated with the effect of mouse experiment toxoplasmosis model evaluation treatment toxplasmosis in pigs drug, while providing the medicament composing prescription for the resisting toxoplasmosis that two work well.
Description
Technical field
The invention belongs to field of medicaments, more particularly to a kind of resisting toxoplasmosis prescription medicine and its screening technique.
Background technology
Toxoplasmosis is a kind of Amphixenosis caused by toxoplasma gondii.It is a kind of universal parasitic former
Worm can infect 200 many animals including people.Body under normal circumstances, arch insect infection is mostly subclinical infection, but right
In immune deficiency or immunosupress person, such as AIDS, organ transplant, malignant tumor patient, arch insect infection may be lethal disease
One of because.The probability of infection of pregnant women toxoplasma is higher, and toxoplasma can be transmitted to fetus by placental barrier, pregnant woman is caused to miscarry,
Infant development deformity, dysnoesia, encephalitis and meningitis etc..For animal, acute toxoplasmosis can cause piglet fever, exhale
Inhale difficult, failure；Fetal death of sow, miscarriage or the weak son of production.
Currently, the medicine of humans and animals toxoplasmosis mainly has：(1) antibiotic of antibiotic macrolides such as sieve
Erythromycin, spiramvcin, azithromycin and lincomycin series antibiotics such as lindamycin, minomycin can be different degrees of
Prevent toxoplasmosis；Atropic can be used for second stage prophylactic after acute toxoplasmosis is treated for quinone；The quinolines promise such as trovafloxacin
Ketone drug is also proved the effect of external resisting toxoplasmosis breeding.(2) drug of anti-folic acid metabolism：Pyrimethamine is considered as
Treat the most effective drug of eye toxoplasmosis；Sulphadiazine can be used for the auxiliary treatment of a toxoplasmosis；Sulfamethoxazole with
TMP, which is used in combination, can treat mouse experiment toxoplasmosis, prevent the generation of chronic toxoplasmic encephalitis, but be difficult to cure completely.(3)
Chinese medicine：Allicin is used in combination with the side's Fu Sulfamethoxazole can efficiently control acute infection toxoplasmosis；Dihydroartemisinine can
Extend the time-to-live of mouse, if with sodium sulfadiazine application, synergistic effect can be generated and quickly remove polypide, effectively prevent
It is recurred after drug withdrawal；Matrine plays the role of inhibiting toxoplasma tachyzoite breeding；It is small that Radix Astragali can extend the infection of low dosage tachyzoite
The time-to-live of mouse.(4) other medicines：Tranquilizer (haloperidol) and mood-stabilizing drug (valproic acid) in vitro can be effectively
Toxoplasma breeding, experiment is inhibited to confirm that the drug for the treatment of severe mental disease is likely to become the new drug candidate for the treatment of toxoplasmosis.
Sterols drug is used in combination with sulphadiazine or pyrimethamine has the effect of resisting toxoplasmosis proliferation.
Invention content
It is an object of the invention to overcome above-mentioned shortcoming and deficiency existing in the prior art, a kind of resisting toxoplasmosis is provided
The screening technique of prescription medicine.The effect of toxplasmosis in pigs drug being treated with mouse experiment toxoplasmosis model evaluation.The present invention
Drug includes sulfadiazine sodium injection, the side's Fu Sulfamethoxazole, lincomycin hydrochloride injection, Sulfamonomethoxime Sodium note
Penetrate liquid, Archie fluorine injection, acetyl spiramycin, pyrimethamine, roxithromycin, sweet wormwood, kuh-seng.
It is yet another object of the invention to provide a kind of resisting toxoplasmosis prescription medicines for having above-mentioned screening to obtain.
The purpose of the invention is achieved by the following technical solution：A kind of screening technique of resisting toxoplasmosis prescription medicine, use are small
Mouse tests the effect of toxoplasmosis model evaluation treatment toxplasmosis in pigs drug；
The effect of toxplasmosis in pigs drug, is treated in the mouse experiment toxoplasmosis model evaluation, includes the following steps：
(1) mouse experiment toxoplasmosis Animal Model：The PYS strain tachyzoites of liquid nitrogen conservation is continuous in Mice Body
Recovery three generations, intraperitoneal inoculation SPF kunming mices, after 72h, cervical dislocation puts to death mouse, with normal saline flushing abdominal cavity, extracts
Peritoneal fluid is counted after dilution with white blood cell count(WBC) plate；The dosage of mouse infection toxoplasma is 1 × 103A tachyzoite/only, ascites
With normal saline dilution at 5 × 103A tachyzoite/mL, every mouse inoculation 0.2mL；
(2) ten kinds of drugs is used to design two experiments, a folk prescription drug test, a prescription medicine examination as medicine
It tests, drug therapy is carried out to different groups of mouse models, the state of mind of mouse is observed during medication；Wherein with 10 mouse
Record each medicine group death condition；3 after infection, grab within 5,7,10,17,24,30 days 2-3 at random from every group only, eye socket blood sampling carries
DNA is taken to carry out PCR amplification；It takes the ascites of mouse to be counted with white blood cell count(WBC) plate, takes the liver of mouse, lungs, heart, spleen group
Internal organs are knitted, extract DNA, and be detected with specific PCR methods；Two experiment the data obtained application SPSS11.5 softwares are carried out
Data analysis；
(3) on the Research foundation of mouse model, new mouse and toxplasmosis in pigs animal model are established, design experiment is used
The good resisting toxoplasmosis drug of effect has been filtered out to be treated；The mental status of observation pig, measures body temperature before experiment；To every pig
Blood was collected, and blood sample is divided to two parts of preservations (anti-freezing and non-anticoagulation)；Body temperature is monitored during experiment, since 4h after infection, often
Day thermometric 2 times counts continued fever；Observe its state of mind, appetite, the situations such as urination and defecation；6 after infection, 11,21 days it is each
Group slaughters 1 pig at random, and every experiment pig vena cava anterior blood sampling, blood are divided to two parts of preservations before slaughtering；It takes and cuts open the ascites for killing pig, liver
Dirty, lungs, hilar lymph node, heart, spleen, mesenteric lymph node tissues are extracted DNA, and are examined with specific PCR methods
It surveys；Realize the screening of resisting toxoplasmosis prescription medicine.
Ten kinds of drugs described in step (2) include that sulfadiazine sodium injection, the side's Fu Sulfamethoxazole, hydrochloric acid woods can be mould
Plain injection, Sulfamonomethoxime Sodium injection, Archie fluorine injection, acetyl spiramycin, pyrimethamine, roxithromycin,
Sweet wormwood, kuh-seng.
Testing result is shown, in the folk prescription drug of resisting toxoplasmosis, lincomycin hydrochloride injection, Archie fluorine injection, blueness
Wormwood artemisia, kuh-seng resisting toxoplasmosis are invalid；Pyrimethamine has certain resisting toxoplasmosis effect, but mouse survival rate is low；Sodium sulfadiazine is noted
Penetrating liquid, the side's Fu Sulfamethoxazole, Sulfamonomethoxime Sodium injection, acetyl spiramycin, roxithromycin has preferable anti-bow
Shape worm effect, wherein Sulfamonomethoxime Sodium injection can thoroughly remove the toxoplasma in tissue with roxithromycin.
Testing result is shown, in the prescription medicine of resisting toxoplasmosis, pair with treatment toxoplasma gondii infection mouse model, group three
(daimeton 500mg/kgd+ pyrimethamine 25mg/kgd+TMP100mg/kgd) and five (compound sulfonamides of group
Jia oxazole 500mg/kgd+ acetyl spiramycin 200mg/kgd) than other medicines group have better resisting toxoplasmosis effect.
Above-mentioned (the daimeton 500mg/kgd+ pyrimethamines 25mg/kgd+TMP100mg/kg of group three
D) and five (side Fu Sulfamethoxazole 500mg/kgd+ acetyl spiramycin 200mg/kgd) of group are used for artificial challenge's pig arch
The treatment of parasitosis can effectively treat artificial challenge's toxplasmosis in pigs, thoroughly remove the polypide in tissue.
A kind of resisting toxoplasmosis composition of medicine is obtained by above-mentioned screening technique, including mass ratio is 500：25:100 sulfanilamide (SN)
Between Sulfamonomethoxine：Pyrimethamine：The pharmaceutical composition of TMP.
Another resisting toxoplasmosis composition of medicine is obtained by above-mentioned screening technique, including mass ratio is 500:200 compound
Sulfamethoxazole：The pharmaceutical composition of acetyl spiramycin.
The present invention has the following advantages and effects with respect to the prior art：
1, the present invention selects the folk prescription drug pair of ten kinds of resisting toxoplasmosis by establishing mouse experiment toxoplasmosis animal model
It is treated, and sulfadiazine sodium injection, the side's Fu Sulfamethoxazole, Sulfamonomethoxime Sodium injection, acetyl spiral are filtered out
Mycin, roxithromycin have preferable resisting toxoplasmosis effect, and wherein Sulfamonomethoxime Sodium injection can be thoroughly with roxithromycin
Remove the toxoplasma in tissue；Mouse model is treated with five prescriptions of ten kinds of folk prescription compatibility of drugs, is filtered out
Prescription three (daimeton 500mg/kgd+ pyrimethamine 25mg/kgd+TMP100mg/kgd) and prescription five
(side Fu Sulfamethoxazole 500mg/kgd+ acetyl spiramycin 200mg/kgd) has better resisting toxoplasmosis than other prescriptions
Effect.
2, the present invention is by establishing mouse model and pig animal model, with five prescriptions of ten kinds of folk prescription compatibility of drugs
It is treated respectively, filters out (the daimeton 500mg/kgd+ pyrimethamines 25mg/kgd+ of prescription three
TMP100mg/kgd) and prescription five (side Fu Sulfamethoxazole 500mg/kgd+ acetyl spiramycin 200mg/kgd) is equal
Artificial challenge's toxplasmosis in pigs can be effectively treated, the polypide in tissue can be thoroughly removed.The prescription medicine can be used for treating pig
Toxoplasmosis is laid a good foundation for further study of Prevention Technique of toxoplasma.
Description of the drawings
Fig. 1：Test the 7th day medicine group one after a mouse infection, group two, the pcr amplification product electrophoretogram for organizing three.Wherein M：
Marker DL 2000；1：Positive control；2-16：Blood, liver, lungs, heart, the spleen of medicine group one；Medicine group two
Blood, liver, lungs, heart, spleen；Blood, liver, lungs, heart, the spleen amplified production of medicine group three；17：Host couple
According to (mouse)；18：Blank control.
Fig. 2：Test the 7th day medicine group four after a mouse infection, group five, the pcr amplification product electrophoretogram for organizing six.M：
Marker DL 2000；1：Positive control；2-16：Blood, liver, lungs, heart, the spleen of medicine group four；Medicine group five
Blood, liver, lungs, heart, spleen；Blood, liver, lungs, heart, the spleen amplified production of medicine group six；17：Host couple
According to (mouse)；18：Blank control.
Fig. 3：Test the 7th day medicine group seven after a mouse infection, group eight, the pcr amplification product electrophoretogram for organizing nine.M：
Marker DL 2000；1：Positive control；2-16：Blood, liver, lungs, heart, the spleen of medicine group seven；Medicine group eight
Blood, liver, lungs, heart, spleen；Blood, liver, lungs, heart, the spleen amplified production of medicine group nine；17：Host couple
According to (mouse)；18：Blank control.
Fig. 4：Test the 7th day medicine group ten after a mouse infection, drug-positive control group pcr amplification product electrophoretogram.
M：Marker DL 2000；1：Positive control；2-11：Blood, liver, lungs, heart, the spleen of medicine group ten；Drug-positive
Blood, liver, lungs, heart, the spleen of control group；12：Host compares (mouse)；13：Blank control.
Fig. 5：Test the 7th day medicine group one after two mouse infections, group two, the pcr amplification product electrophoretogram for organizing three.M：
Marker DL 2000；1：Positive control；2-16：Blood, liver, lungs, heart, the spleen of medicine group one；Medicine group two
Blood, liver, lungs, heart, spleen；Blood, liver, lungs, heart, the spleen amplified production of medicine group three；17：Host couple
According to (mouse)；18：Blank control.
Fig. 6：Test the 7th day medicine group four after two mouse infections, group five, the pcr amplification product electrophoretogram for organizing six.M：
Marker DL 2000；1：Positive control；2-16：Blood, liver, lungs, heart, the spleen of medicine group four；Medicine group five
Blood, liver, lungs, heart, spleen；The amplified production of six blood of medicine group, liver, lungs, heart, spleen；17：Host couple
According to (mouse)；18：Blank control.
Fig. 7：Test the 7th day medicine group seven after two mouse infections, group eight, the pcr amplification product electrophoretogram for organizing nine.M：
Marker DL 2000；1：Positive control；2-16：Blood, liver, lungs, heart, the spleen of medicine group seven；Medicine group eight
Blood, liver, lungs, heart, spleen；The amplified production of nine blood of medicine group, liver, lungs, heart, spleen；17：Host couple
According to (mouse)；18：Blank control.
Fig. 8：Test the 7th day medicine group ten after two mouse infections, drug-positive control group pcr amplification product electrophoretogram.
M：Marker DL 2000；1：Positive control；2-11：Blood, liver, lungs, heart, the spleen of medicine group ten；Drug-positive
Blood, liver, lungs, heart, the spleen of control group；12：Host compares (mouse)；13：Blank control.
Fig. 9：The pcr amplification product of 7th day medicine group one, group two, drug-positive control group after mouse model infection
Electrophoretogram.M：Marker DL 2000；1：Positive control；2-16：Blood, liver, lungs, heart, the spleen of medicine group one；Medicine
Blood, liver, lungs, heart, the spleen of object group two；The blood of drug-positive control group, liver, lungs, heart, spleen amplification
Product；17：Host compares (mouse)；18：Blank control.
Figure 10：The pcr amplification product electrophoretogram of 5th day drug-positive control group after the administration of pig animal model.M：Marker
DL 2000；1：Positive control；2-7：Blood, liver, lungs, hilar lymph node, heart, the spleen of drug-positive control group；8：
Host compares (pig)；9：Blank control.
Figure 11：The pcr amplification product electrophoretogram of 9th day drug-positive control group after the administration of pig animal model.M：Marker
DL 2000；1：Positive control；2-13：Blood, liver, lungs, hilar lymph node, heart, the spleen of drug-positive control group (3#)
It is dirty；Drug-positive control group (4#) blood, liver, lungs, hilar lymph node, heart, spleen；14：Host compares (pig)；15：
Blank control.
Specific implementation mode
Present invention will now be described in further detail with reference to the embodiments and the accompanying drawings, but embodiments of the present invention are unlimited
In this.
The foundation of 1 mouse experiment toxoplasmosis animal model of embodiment
By the PYS strain tachyzoites of liquid nitrogen conservation, continuous recovery three generations, intraperitoneal inoculation SPF kunming mices connect in Mice Body
After kind 72h, cervical dislocation puts to death mouse, and appropriate normal saline flushing abdominal cavity takes out cleaning solution, leucocyte is used after appropriate dilution
Tally counts.The dosage of mouse infection toxoplasma is 1 × 103A tachyzoite/only, ascites is with normal saline dilution at 5 × 103
A tachyzoite/mL, every mouse inoculation 0.2mL, mixing before injecting.The time of tachyzoite in vitro is no more than 2h.
2 therapeutic scheme of embodiment experiment one
(1) experiment grouping：Experiment mice is randomly divided into 13 groups, including 10 medicine groups, infection not treatment group's (positive control
Group), injection blank control group and gavage blank control group, every group of 26 mouse.The experimental observation phase is 30 days.
(2) infective dose：PYS plants of tachyzoites 1 × 103A/mouse.
(3) trial drug and medication are shown in Table 1：
The drug grouping of the experiment of table 1 one and medication
Embodiment 3 tests the comparison of an each group mouse survival time and protective rate
Each group mouse survival situation from since the mouse infection, and record death condition, mouse survival 30 days or more
Time-to-live is in terms of 30 days.The mean survival time and protective rate for testing an each group mouse are shown in Table 2：
Table 2 tests a mouse mean survival time and protective rate
| Group | Mean survival time (day) | Protective rate (%) |
| Positive controls | 8.07±0.25a | 0a |
| Blank control group | 30.00±0.00b | 100b |
| Group one | 27.54±1.31b | 70b |
| Group two | 29.38±0.62b | 90b |
| Group three | 8.14±0.11a | 0a |
| Group four | 30.00±0.00b | 100b |
| Group five | 9.17±0.03a | 0a |
| Group six | 29.06±0.63b | 80b |
| Group seven | 17.62±2.88c | 30a |
| Group eight | 28.96±0.71b | 70b |
| Group nine | 9.17±0.14a | 0a |
| Group ten | 8.89±0.27a | 0a |
Note：Same column difference indicates that with indicating that difference is not notable, difference indicates digital upper right corner institute marking-up parent phase with a, b, c
Significant difference (p<0.05), colleague does not make comparisons
From table 2 it is known that medicine group one, group two, group four, group six, the mouse mean survival time and protective rate for organizing eight
With the more equal significant difference (p of positive controls<0.05)；Medicine group three, group five, group seven, group nine, the mouse Average Survival for organizing ten
Time and protective rate and the more equal significant difference (p of blank control group<0.05).Non- treatment group, that is, positive controls the mouse of infection
Mean survival time is 8.07 days, and mouse is all dead in 10 days.
Embodiment 4, which is tested an each group mouse ascites polypide and counted, to be compared
Test to cut open for the after mouse infection the 3rd day, 5 days, 7 days, 10 days, 17 days, 24 days, 30 days and kill mouse, cut open kill it is small
Mouse extracts ascites, is counted with white blood cell count(WBC) plate, the results are shown in Table 3, table 4：
Table 3 tests mouse ascites polypide enumeration data analysis
| Group | d3 | d5 | d7 |
| Positive control | 74400±600a | 268500±4350 | 10600000±275000 |
| Blank control | 0b | 0b | 0b |
| Group one | 3500±3500b | 7562±562b | 47700±900b |
| Group two | 0b | 1912±37b | 20250±750b |
| Group three | 17000±9000 | 40700±16700 | 8100000±540000c |
| Group four | 0b | 975±b975b | 37200±1550b |
| Group five | 5500±2000b | 34000±14000 | 374000±26000b |
| Group six | 1875±1875b | 6375±b4125b | 86125±60900b |
| Group seven | 750±750b | 3425±325b | 25650±2850b |
| Group eight | 2125±2125b | 4000±2000b | 8125±3125b |
| Group nine | 2275±725b | 19450±4750b | 61875±20625b |
| Group ten | 1500±1500b | 41625±3375b | 1505000±105000d |
Note：Same column difference indicates that digital upper right corner institute marking-up parent phase is not notable with expression difference, different tables with a, b, c, d
Show significant difference (p<0.05), colleague does not make comparisons
Table 4 tests mouse ascites polypide enumeration data analysis
| Group | d10 | d17 | d24 | d30 |
| Positive control | ||||
| Blank control | 0ab | 0a | 0 | 0 |
| Group one | 0ab | 0a | 0 | 0 |
| Group two | 0ab | 2687±438 | 0 | 0 |
| Group three | ||||
| Group four | 0ab | 0a | 0 | 0 |
| Group five | ||||
| Group six | 0ab | 3375±250 | 0 | 0 |
| Group seven | 0ab | 0a | 0 | 0 |
| Group eight | 2150±100b | 0a | 0 | 0 |
| Group nine | 1400000±100000c | |||
| Group ten | 3675000±375000d |
Note：Same column difference indicates that digital upper right corner institute marking-up parent phase is not notable with expression difference, different tables with a, b, c, d
Show significant difference (p<0.05), colleague does not make comparisons
It was found from table 3, table 4：Positive controls are also gradually increased with the increase for infecting number of days, ascites polypide quantity.Respectively
Medicine group after infection the 7th day when, ascites polypide quantity is most；At the end of medicine group to drug delivery regimen group one, group two, group four,
Group six, seven microscopies of group do not observe Toxoplasma.The higher medicine group one of protective rate organizes the small of two, group four, group six and group eight
Mouse ascites fluid polypide quantity is less in different number of days.
Embodiment 5 tests a specific PCR testing result
Take after infection the 3rd day, 5 days, 7 days, 10 days, 17 days, 24 days, 30 days each group mouse bloods, liver, lungs, the heart
Dirty, brain and spleen sample carry out PCR detections.Wherein the brain tissue sample of each group different number of days does not amplify the bow of about 250bp
Shape worm specific band；The whole samples of 3rd day and the 17th day each survival group do not amplify special article of the toxoplasma of about 250bp yet
Band；Not in table, an an example goes out the above testing result.Remaining each group testing result is shown in Table 5, table 6 and table 7, wherein the 7th day each group
Testing result see attached drawing 1, attached drawing 2, attached drawing 3 and attached drawing 4.
5th day, the 7th day PCR testing result after the infection of 5 each group of table
Note："+" indicates that PCR testing results are positive；"-" indicates that PCR testing results are negative
10th day PCR testing result after the infection of 6 each group of table
| Group | Blood | Liver | Lung | The heart | Spleen |
| Group one | |||||
| Group two | |||||
| Group four | |||||
| Group six | |||||
| Group seven | + | ||||
| Group eight | |||||
| Group nine | + | + | + | ||
| Group ten | + | + | + | ||
| It is positive right | + | + | + | + | + |
| Blank pair |
Note："+" indicates that PCR testing results are positive；"-" indicates that PCR testing results are negative
24th day, the 30th day PCR testing result after the infection of 7 each group of table
Note："+" indicates that PCR testing results are positive；"-" indicates that PCR testing results are negative
From ascites count results and PCR testing results it is found that ascites polypide quantity is relatively large number of be infection after the 7th day,
The highest recall rate of PCR detection each sample is also the 7th day after infection；Five of protective rate and positive controls significant difference
Medicine group group one, group two, the sample number of eight detection of group four, group six and group are fewer than positive controls and other several medicine groups, say
Bright these types drug has the effect of stronger resisting toxoplasmosis；When off-test, medicine group one, group two, group six still have portion of tissue
Sample can amplify the toxoplasma specific band of about 250bp, illustrate that these three drugs have the effect for inhibiting toxoplasma breeding, but not
It can the fully erased toxoplasma being present in tissue.
Embodiment 6 tests a mouse spleen index
Experiment cuts open the mouse killed and first weighs, and takes its spleen, weighs the weight of spleen, the weight and body of every mouse spleen
The ratio of weight is the spleen index of the mouse.The statistical result of each group mouse spleen index is shown in Table 8, table 9.
Table 8 tests a mouse spleen index data analysis
Note：Same column difference indicates that digital upper right corner institute marking-up parent phase is not notable with expression difference, different tables with a, b, c, d
Show significant difference (p<0.05), colleague does not make comparisons.
Table 9 tests a mouse spleen index data analysis
Note：Same column difference indicates that digital upper right corner institute marking-up parent phase is not notable with expression difference, different with a, b, c, d, e
Indicate significant difference (p<0.05), colleague does not make comparisons.
From table 8, table 9 it is found that each infected group spleen index all there were significant differences with blank control group to varying degrees；To sense
The 10th day after dye, the 17th day, the mouse spleen index of each group with blank control group significant difference (p<0.05)；To off-test
When, only the higher medicine group two of protective rate, group four, the spleen index for organizing eight and blank control group are without significant difference；Medicine group one,
Group six, the group seven and equal significant difference (p of blank control group<0.05), the protective rate of this result and mouse height substantially conforms to.
In summary several indexs, this research will be between the preferable medicaments compound Sulfamethoxazole of resisting toxoplasmosis effect, sulfanilamide (SN)
Sulfamonomethoxine, acetyl spiramycin, roxithromycin, pyrimethamine carry out prescription, in testing the experiment of two prescriptions, further investigate
Its resisting toxoplasmosis effect.
6 therapeutic scheme of embodiment experiment two
(1) experiment grouping：Experiment mice is randomly divided into 12 groups, including 10 medicine groups, infection not treatment group's (positive control
Group), blank control group, every group of 32 mouse.The experimental observation phase is 30 days.
(2) infective dose：PYS plants of tachyzoites 1 × 103A/mouse.
(3) trial drug and medication are shown in Table 10：
The drug grouping of the experiment of table 10 two and medication
Embodiment 7 tested for two each group mouse survival times and protective rate compares
Each group mouse survival situation from since the mouse infection, and record death condition, mouse survival 30 days or more
Time-to-live is in terms of 30 days.The mean survival time and protective rate for testing two each group mouse are shown in Table 11.
Table 11 tests two mouse mean survival times and protective rate
| Group | Mean survival time | Protective rate |
| Positive controls | 8.17±0.32a | 0%a |
| Blank control group | 30.00±0.00b | 100%b |
| Group one | 30.00±0.00b | 100%b |
| Group two | 30.00±0.00b | 100%b |
| Group three | 30.00±0.00b | 100%b |
| Group four | 30.00±0.00b | 100%b |
| Group five | 30.00±0.00b | 100%b |
| Group six | 30.00±0.00b | 100%b |
| Group seven | 27.90±6.64c | 90%b |
| Group eight | 30.00±0.00b | 100%b |
| Group nine | 30.00±0.00b | 100%b |
| Group ten | 30.00±0.00b | 100%b |
Note：Same column difference indicates that with indicating that difference is not notable, difference indicates digital upper right corner institute marking-up parent phase with a, b, c
Significant difference (p<0.05), colleague does not make comparisons.
In experiment two, all death in the 9th day after infection of positive controls mouse, mean survival time is 8.17 days.
The mouse mean survival time of medicine group seven is 27.9 days, with positive controls and the equal significant difference (p of blank control group<
0.05)；Protective rate is up to 90%, with positive controls protective rate significant difference (p<0.05).The mouse of remaining 9 medicine group is protected
Rate reaches 100%, and the effect of medicament protection mouse survival is notable.
Embodiment 8, which is tested two each group mouse ascites polypides and counted, to be compared
The 3rd day after mouse infection, 5 days, 7 days, 10 days, 17 days, 24 days, 30 days each groups cut open kill mouse 3 at random, extraction is cutd open
The ascites of mouse is killed, ascites is counted with white blood cell count(WBC) plate, and ascites polypide enumeration data analysis result is shown in Table 12, table 13.
Table 12 tests the analysis of two mouse ascites polypide enumeration datas
| Group | d3 | d5 | d7 |
| Positive control | 9250±2642a | 1900000±642 | 3746667±86 |
| Blank control | 0b | 0b | 0b |
| Group one | 1417±712bc | 7800±600b | 26000±1701 |
| Group two | 1541±771bc | 8417±1529b | 18083±6561 |
| Group three | 2833±622bc | 3583±1210b | 2003±259b |
| Group four | 3250±1146c | 19667±1481b | 2337±586b |
| Group five | 2416±1446 | 17167±2237b | 3043±736b |
| Group six | 3042±730bc | 10083±1516b | 16000±1391 |
| Group seven | 1958±110bc | 27667±12548 | 10543±2846 |
| Group eight | 3833±1104c | 31000±8386b | 10000±5393 |
| Group nine | 4833±441c | 30500±1258b | 28667±1856 |
| Group ten | 3667±882c | 22333±7310b | 9917±6439b |
Note：Same column difference indicates that with indicating that difference is not notable, difference indicates digital upper right corner institute marking-up parent phase with a, b, c
Significant difference (p<0.05), colleague does not make comparisons.
Table 13 tests the analysis of two mouse ascites polypide enumeration datas
| Group | d10 | d17 | d24 | d30 |
| Positive control | ||||
| Blank control | 0abc | 0a | 0 | 0 |
| Group one | 1917±208abc | 2667±441ab | 0 | 0 |
| Group two | 708±708ac | 1303±39ab | 0 | 0 |
| Group three | 2417±83bc | 2003±72ab | 0 | 0 |
| Group four | 833±833abc | 1877±192ab | 0 | 0 |
| Group five | 0abc | 1333±726ab | 0 | 0 |
| Group six | 3208±1208bd | 17583±8827c | 0 | 0 |
| Group seven | 3500±1000bd | 10500±1893 | 0 | 0 |
| Group eight | 3000±750bd | 15000±0c | 0 | 0 |
| Group nine | 4900±208d | 7503±217ab | 0 | 0 |
| Group ten | 3083±712bd | 6172±1230b | 0 | 0 |
Note：Same column difference indicates that digital upper right corner institute marking-up parent phase is not notable with expression difference, different tables with a, b, c, d
Show significant difference (p<0.05), colleague does not make comparisons.
From table 12, table 13 it is found that positive controls are with the increase of infection time, ascites polypide quantity increases.Each medicine group
Ascites polypide quantity and positive controls significant difference (p<0.05).Medicine group six, group seven, group eight, group nine, group ten are infecting
The 17th day ascites polypide quantity is higher than preceding 5 prescription medicine groups afterwards；24 days microscopies have not seen Toxoplasma after to infection.
The 7th day after infection, when the ascites polypide quantity of majority group is in peak, prescription medicine group three, group four, the ascites polypide number for organizing five
Amount is fewer than other infected groups, illustrates that the effect of resisting toxoplasmosis is rapider than other groups.Compared with group five, group five exists prescription medicine group four
In addition to after infection the 7th day, ascites polypide quantity is fewer than medicine group four.
Embodiment 9 tests two specific PCR testing results
Take after infection the 3rd day, 5 days, 7 days, 10 days, 17 days, 24 days, 30 days each group mouse bloods, liver, lungs, the heart
Dirty, spleen and the 30th day brain tissue sample carry out PCR detections.Testing result is shown in Table 14~table 16.
3rd day, the 5th day PCR testing result after the infection of 14 each group of table
Note："+" indicates that PCR testing results are positive；"-" indicates that PCR testing results are negative.
10th day, 17 days PCR testing results after the infection of 15 each group of table
Note："+" indicates that PCR testing results are positive；"-" indicates that PCR testing results are negative
24th day, 30 days PCR testing results after the infection of 16 each group of table
Note："+" indicates that PCR testing results are positive；"-" indicates that PCR testing results are negative
From 14~table of table 16 it is found that each group the 7th day PCR can amplify the sample of toxoplasma specific band most after infection
PCR does not expand in more (result is shown in 5~attached drawing of attached drawing 8), the wherein group two of ascites polypide negligible amounts, group four, each sample of group five
Increase to specific band；To when off-test, medicine group eight organizes nine brain tissue PCR and can amplify toxoplasma specific band, group
One, group two, group eight, group nine have sample segment PCR that can expand to specific band.
Embodiment 10 tests two mouse spleen index
The spleen index for testing two each group mouse is shown in Table 17, table 18.
Table 17 tests two mouse spleen index data analyses
| Group | d3 | d5 | d7 | d10 |
| It is positive right | 0.0061±0.00 | 0.0081±0.00 | 0.0069±0.0 | |
| Blank pair | 0.0043±0.00 | 0.0027±0.00 | 0.0038±0.0 | 0.0032±0.00 |
| Group one | 0.0038±0.00 | 0.0029±0.00 | 0.0043±0.0 | 0.0049±0.00 |
| Group two | 0.0038±0.00 | 0.0051±0.00 | 0.0050±0.0 | 0.0052±0.00 |
| Group three | 0.0034±0.00 | 0.0036±0.00 | 0.0059±0.0 | 0.0040±0.00 |
| Group four | 0.0051±0.00 | 0.0043±0.00 | 0.0052±0.0 | 0.0043±0.00 |
| Group five | 0.0037±0.00 | 0.0046±0.00 | 0.0047±0.0 | 0.0063±0.00 |
| Group six | 0.0050±0.00 | 0.0037±0.00 | 0.0058±0.0 | 0.0104±0.00 |
| Group seven | 0.0038±0.00 | 0.0041±0.00 | 0.0057±0.0 | 0.0045±0.00 |
| Group eight | 0.0047±0.00 | 0.0057±0.00 | 0.0060±0.0 | 0.0041±0.00 |
| Group nine | 0.0035±0.00 | 0.0044±0.00 | 0.0061±0.0 | 0.0071±0.00 |
| Group ten | 0.0041±0.00 | 0.0059±0.00 | 0.0042±0.0 | 0.0043±0.00 |
Note：Same column difference indicates that digital upper right corner institute marking-up parent phase is not notable with expression difference, different tables with a, b, c, d
Show significant difference (p<0.05), colleague does not make comparisons.
Table 18 tests two mouse spleen index data analyses
| Group | d17 | d24 | d30 |
| It is positive right | |||
| Blank pair | 0.0044±0.000 | 0.0051±0.000 | 0.0032±0.000 |
| Group one | 0.0078±0.000 | 0.0071±0.000 | 0.0032±0.000 |
| Group two | 0.0054±0.001 | 0.0045±0.000 | 0.0033±0.000 |
| Group three | 0.0085±0.001 | 0.0047±0.000 | 0.0030±0.000 |
| Group four | 0.0036±0.000 | 0.0036±0.000 | 0.0035±0.000 |
| Group five | 0.0046±0.000 | 0.0038±0.000 | 0.0035±0.001 |
| Group six | 0.0037±0.000 | 0.0025±0.000 | 0.0026±0.000 |
| Group seven | 0.0039±0.000 | 0.0034±0.000 | 0.0029±0.000 |
| Group eight | 0.0051±0.000 | 0.0032±0.000 | 0.0037±0.000 |
| Group nine | 0.0039±0.000 | 0.0033±0.000 | 0.0038±0.000 |
| Group ten | 0.0052±0.000 | 0.0033±0.000 | 0.0035±0.000 |
Note：Same column difference indicates that digital upper right corner institute marking-up parent phase is not notable with expression difference, different tables with a, b, c, d
Show significant difference (p<0.05), colleague does not make comparisons.
From table 17, table 18 it is found that each medicine group different number of days occurred with blank control significant difference, illustrate to feel
Even if contaminating the mouse medication of toxoplasma, the immune level of body changes；Remove medicine group one, group within the 17th day after to infection
Three with outside blank control group significant difference, remaining each group is with blank control group without significant difference；To when off-test, each medicine group
The spleen index of mouse is with blank control group without significant difference.
Embodiment 11 tests two mouse thymus indexes
Thymus index is similar to spleen index computational methods, is the ratio of the thymic weight and weight of mouse.Each medicine group
Thymus index is shown in Table 19, table 20.
Table 19 tests the analysis of two mouse thymus exponent datas
| Group | d3 | d5 | d7 | d10 |
| Positive controls | 0.0047±0.0006a | 0.0068±0.0002 | 0.0040±0.0005ab | |
| Blank control group | 0.0070±0.0001b | 0.0059±0.0001 | 0.0042±0.0001ab | 0.0051±0.0001ac |
| Group one | 0.0058±0.0013ab | 0.0032±0.0006c | 0.0032±0.0003ab | 0.0035±0.0008ab |
| Group two | 0.0041±0.0003ac | 0.0038±0.0007c | 0.0046±0.0005abc | 0.0045±0.0011abc |
| Group three | 0.0027±0.0005c | 0.0033±0.0004c | 0.0039±0.0010ab | 0.0038±0.0004ab |
| Group four | 0.0043±0.0003a | 0.0043±0.0004c | 0.0047±0.0010abc | 0.0034±0.0005ab |
| Group five | 0.0043±0.0007c | 0.0051±0.0008b | 0.0062±0.0003c | 0.0060±0.0007ac |
| Group six | 0.0041±0.0004ac | 0.0031±0.0003c | 0.0051±0.0003abc | 0.0052±0.0010abc |
| Group seven | 0.0027±0.0001c | 0.0030±0.0006c | 0.0049±0.0005abc | 0.0037±0.0003ab |
| Group eight | 0.0032±0.0002ac | 0.0043±0.0003c | 0.0041±0.0010ab | 0.0044±0.0005abc |
| Group nine | 0.0039±0.0001c | 0.0033±0.0007c | 0.0055±0.0001abc | 0.0050±0.0001abc |
| Group ten | 0.0042±0.0002ac | 0.0054±0.0004b | 0.0058±0.0005bc | 0.0058±0.0008ac |
Note：Same column difference indicates that with indicating that difference is not notable, difference indicates digital upper right corner institute marking-up parent phase with a, b, c
Significant difference (p<0.05), colleague does not make comparisons.
Table 20 tests the analysis of two mouse thymus exponent datas
| Group | d17 | d24 | d30 |
| Positive controls | |||
| Blank control group | 0.0047±0.0001ab | 0.0061±0.0001ab | 0.0022±0.0002a |
| Group one | 0.0057±0.0004ab | 0.0070±0.0005b | 0.0037±0.0008a |
| Group two | 0.0058±0.0005ab | 0.0042±0.0000c | 0.0038±0.0005a |
| Group three | 0.0073±0.0001c | 0.0039±0.0006c | 0.0040±0.0053a |
| Group four | 0.0029±0.0002d | 0.0050±0.0007ac | 0.0023±0.0017a |
| Group five | 0.0060±0.0000abc | 0.0059±0.0005ab | 0.0033±0.0001a |
| Group six | 0.0045±0.0008ab | 0.0033±0.0001cd | 0.0020±0.0002a |
| Group seven | 0.0040±0.0001ad | 0.0052±0.0001ac | 0.0030±0.0004a |
| Group eight | 0.0053±0.0001ab | 0.0026±0.0001d | 0.0036±0.0004a |
| Group nine | 0.0061±0.0012bc | 0.0036±0.0001cd | 0.0025±0.0007a |
| Group ten | 0.0068±0.0004bc | 0.0057±0.0006a | 0.0017±0.0003a |
Note：Same column difference indicates that digital upper right corner institute marking-up parent phase is not notable with expression difference, different tables with a, b, c, d
Show significant difference (p<0.05), colleague does not make comparisons.
From table 19, table 20 it is found that mouse the 3rd day to the 5th day after infection, in addition to individual drugs group, most medicine groups
Mouse thymus index and positive controls and blank control group significant difference (p ＜ 0.05)；The 7th day after to infection, medicine group is removed
Outside five, the mouse thymus index and positive controls and blank control group of each medicine group are without significant difference difference；It is tied to experiment
Shu Shi, the thymus index and blank control group of each medicine group mouse are without significant difference.
The effect of prescription medicine Infection Toxoplasma gondii has mainly been investigated in experiment two.Medicine group one to group five is prescription medicine
Group, in summary several index results show：5 prescription medicines can effectively treat mouse experiment toxoplasmosis, to mouse
Protective rate reaches 100%；Prescription medicine group three (daimeton+pyrimethamine+TMP) and five (compound sulfonamide first of group
Oxazole+acetyl spiramycin) there is relatively good resisting toxoplasmosis effect.Therefore, (the first between sulfanilamide (SN) of medicine group three is chosen in this research
Oxygen pyrimidine+pyrimethamine+TMP) and five (side's Fu Sulfamethoxazole+acetyl spiramycin) two prescription medicines are organized in next step
The treatment of artificial challenge's toxplasmosis in pigs.
12 mouse of embodiment and toxplasmosis in pigs Animal Model
By the PYS strain tachyzoites of liquid nitrogen conservation, continuous recovery three generations, intraperitoneal inoculation SPF kunming mices connect in Mice Body
After kind 72h, cervical dislocation puts to death mouse, and appropriate normal saline flushing abdominal cavity takes out cleaning solution, leucocyte is used after appropriate dilution
Tally counts.Mouse infection toxoplasma is to be injected intraperitoneally 1 × 103A tachyzoite/only, ascites with normal saline dilution at 5 ×
103A tachyzoite/mL, every mouse inoculation 0.2mL, mixing before injecting.Pig toxoplasma gondii infection is to be injected intraperitoneally 1 × 107A speed is grown
Son/head, ascites is with normal saline dilution at 2 × 106A tachyzoite/mL, every pig infect 5mL, mixing before injecting.Tachyzoite exists
The external time is no more than 2h.
13 drug therapy testing program of embodiment
(1) therapeutic scheme of mouse experiment toxoplasmosis
Experiment grouping：Experiment mice is randomly divided into 4 groups, including 2 medicine groups, infection not treatment group's (positive controls),
Blank control group, every group of 22 mouse.The experimental observation phase is 20 days.
Infective dose：PYS plants of tachyzoites 1 × 103A/mouse.
Trial drug and medication are shown in Table 21：
The medicine and medication of 21 mouse model of table
(2) therapeutic scheme of artificial challenge's toxplasmosis in pigs
Experiment grouping：Experiment pig is randomly divided into 4 groups, wherein 2 medicine groups, infection not treatment group's (positive controls)
Each 3, blank control group 2.The experimental observation phase is 20 days.
Infective dose：PYS plants of tachyzoites 1 × 107A/head.
Trial drug and medication are shown in Table 22.
The medicine and medication of 22 toxplasmosis in pigs of table
The test result of 14 mouse model toxoplasmosis of embodiment treatment
(1) comparison of mouse survival time and protective rate
The experimental observation phase is 20 days, and each group mouse mean survival time is shown in Table 23 with protective rate.
23 mouse mean survival time of table and protective rate
| Group | Mean survival time | Protective rate |
| Positive controls | 8.52±0.26a | 0%a |
| Blank control group | 20.00±0.00b | 100%b |
| Group one | 20.00±0.00b | 100%b |
| Group two | 19.90±0.10b | 90%b |
Note：Same column difference indicates that for digital upper right corner institute marking-up parent phase with indicating that difference is not notable, difference indicates poor with a, b
Different significantly (p<0.05), colleague does not make comparisons；The time-to-live of mouse survival 20 days or more is in terms of 20 days
As known from Table 23, all death in the 9th day after infection of positive controls mouse, mean survival time are 8.25 days；
Group one, organize two mean survival time and protective rate with positive controls significant difference (p<0.05), wherein group one is than two tool of group
There is the effect of preferably protection mouse survival, protective rate is up to 100%.
(2) comparison that mouse ascites polypide counts
Each group mouse ascites polypide number is shown in Table 24.
24 mouse ascites polypide of table, which counts, compares
| Group | d3 | d5 | d7 | d10 | d20 |
| Positive control | 9291±708a | 54333±13860 | 200000±20132 | ||
| Blank control | 0b | 0b | 0b | 0 | 0 |
| Group one | 3500±1250 | 2000±0b | 5667±1667b | 0 | 0 |
| Group two | 1958±110bc | 7250±2553b | 3583±917b | 0 | 0 |
Note：Same column difference indicates that with indicating that difference is not notable, difference indicates digital upper right corner institute marking-up parent phase with a, b, c
Significant difference (p<0.05), colleague does not make comparisons
As known from Table 24, positive controls the 7th day ascites polypide quantity after infection is most；Medicine group one, group two are in sense
Start ascites microscopy and do not find polypide within the 10th day after dye.
(3) mouse samples PCR testing results
Each group mouse samples the 3rd day after infection, 10 days, do not expand to specific band in 20 days PCR detection.Each group
The 5th day after infection, 7 days testing results be shown in Table 25 and attached drawing 9.
5th day, the 7th day PCR testing result after the infection of 25 each group of table
Note："+" indicates that PCR testing results are positive；"-" indicates that PCR testing results are negative
As can be known from Table 25, the sample that can be expanded in positive controls to specific band is more compared with medicine group；One He of medicine group
Group two has sample segment that can amplify specific band on the 7th day after infection.
(4) comparison of mouse spleen index, thymus index
The spleen index and thymus index of each group mouse different number of days are shown in Table 26, table 27：
26 mouse spleen index data analysis of table
| Group | d3 | d5 | d7 | d10 | d20 |
| It is positive right | 0.0046±0.00 | 0.0035±0.00 | 0.0076±0.00 | ||
| Blank pair | 0.0032±0.00 | 0.0034±0.00 | 0.0032±0.00 | 0.0049±0.00 | 0.0066±0.00 |
| Group one | 0.0035±0.00 | 0.0024±0.00 | 0.0033±0.00 | 0.0058±0.00 | 0.0036±0.00 |
| Group two | 0.0039±0.00 | 0.0044±0.00 | 0.0055±0.00 | 0.0053±0.00 | 0.0134±0.00 |
Note：Same column difference indicates that with indicating that difference is not notable, difference indicates digital upper right corner institute marking-up parent phase with a, b, c
Significant difference (p<0.05), colleague does not make comparisons
27 mouse thymus exponent data of table is analyzed
| Group | d3 | d5 | d7 | d10 | d20 |
| Positive control | 0.0058±0.0 | 0.0047±0.00 | 0.0044±0.00 | ||
| Blank control | 0.0049±0.0 | 0.0056±0.00 | 0.0062±0.00 | 0.0061±0.00 | 0.0033±0.00 |
| Group one | 0.0035±0.0 | 0.0027±0.00 | 0.0036±0.00 | 0.0043±0.00 | 0.0035±0.00 |
| Group two | 0.0057±0.0 | 0.0053±0.00 | 0.0053±0.00 | 0.0054±0.00 | 0.0028±0.00 |
Note：Same column difference indicates that with indicating that difference is not notable, difference indicates digital upper right corner institute marking-up parent phase with a, b, c
Significant difference (p<0.05), colleague does not make comparisons.
From table 26, table 27 it is found that when off-test, spleen index and the blank control group significant difference of two mouse of medicine group
(p<0.05)；The thymus index of two mouse of medicine group one and group is with blank control group without significant difference.
In summary several indexs, this test result are：The toxoplasmosis that two medicine groups treat mouse model is effective,
The resisting toxoplasmosis curative effect of medicine group one (daimeton+pyrimethamine+TMP) is slightly better than two (compound sulfonamide first of group simultaneously
Oxazole+acetyl spiramycin).
15 artificial challenge's toxplasmosis in pigs test result of embodiment
(1) the toxplasmosis in pigs animal model artificial onset course of disease
The pig of all toxoplasma gondii infections starts body temperature raising for 24 hours after infection, and 48h infection temperature of pig body exists to after infecting
There are spiritual depressed, the symptoms such as expiratory dyspnea in 40 DEG C or more, up to 41.5 DEG C, while loss of appetite.The 3rd day after infection,
Positive controls maximum temperature is up to 42.4 DEG C, and loss of appetite；Two medicine group pig appetites start to restore normal, and body temperature is also begun to
Decline, for the highest temperature up to 40.2 DEG C, lowest temperature drops to 39.4 DEG C.The 4th day after infection, two medicine group temperature of pig body restore normal, diet
It is intended to restore normal.The 8th day after infection, there is ataxia in remaining 2 positive controls pigs, have sharp ears, lip, tail end, at anus,
There is purplish-red macula in limb end.The 9th day after to infection, 2 positive controls pigs cannot stand, no appetite, but still have drink to be intended to,
Mucous membrane is carried in excrement.Pig is played on the outside of back leg from buttocks and all purplish-red maculas of limb end.The 10th day after infection, 2 sun
Property control group pig it is all dead, high temperature continues to death.During experiment, medicine group is without lethal pig, 2 pig bodies of blank control group
Temperature is normal always with body condition.
(2) pig sample P CR testing results
Medicine group one, group two 5 days upon administration, 10 days, 20 days testing results be negative findings.Positive controls knot
Fruit is shown in Table 28, attached drawing 10 and attached drawing 11.It cuts open in the sample that the positive controls killed are taken within the 5th day after administration, blood, liver, lung
Dirty, hilar lymph node, spleen can amplify the toxoplasma specific band of about 250bp；The 9th day after administration, positive controls are remaining
Both ends are all dead, wherein in a pig sample, blood, liver, lungs, hilar lymph node, heart, spleen can amplify about
The toxoplasma specific band of 250bp；In addition to heart is not detected, remaining 5 sample also amplifies the toxoplasma of about 250bp for other end
Specific band.
28 pig sample P CR testing results of table
| Group | Blood | Liver | Lungs | Hilar lymph node | Heart | Spleen |
| Positive controls (d5) | + | + | + | + | + | |
| Positive controls (d93#) | + | + | + | + | + | |
| Positive controls (d94#) | + | + | + | + | + | + |
Note："+" indicates that PCR testing results are positive；"-" indicates that PCR testing results are negative
The experiment pig of positive controls after infection the 10th day it is all dead, medicine group one organizes two experiment pig without death,
It is killed until all being cutd open when off-test.PCR testing results are organized two sample and are not expanded in different time it is found that medicine group one
Go out specific band.According to result above it is found that two (compounds of medicine group one (daimeton+pyrimethamine+TMP) and group
Sulfamethoxazole+acetyl spiramycin) two medicine groups treatment artificial challenge's toxplasmosis in pigs it is effective, the treatment with mouse model
Effect is consistent, but fails to compare the difference of two curative effect of medication.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other it is any without departing from the spirit and principles of the present invention made by changes, modifications, substitutions, combinations, simplifications,
Equivalent substitute mode is should be, is included within the scope of the present invention.
Claims (1)
1. a kind of resisting toxoplasmosis composition of medicine, it is characterised in that：It is 500 that the resisting toxoplasmosis composition of medicine, which is by mass ratio,：
25:100 daimeton：Pyrimethamine：The pharmaceutical composition of TMP compositions；
The pharmaceutical composition is free of other adjunct ingredients.
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| WO2002074242A2 (en) * | 2001-03-16 | 2002-09-26 | Tyler Curiel | Inhibition of toxoplasma gondii) replication by pyridinylimidazoles |
| CN101450055A (en) * | 2007-11-29 | 2009-06-10 | 天津瑞普生物技术集团有限公司 | Soluble powder for treating livestock and poultry bacterial infection and parasitic disease |
| CN101816663A (en) * | 2009-02-26 | 2010-09-01 | 河南惠通天下动物药业有限公司 | Medicinal composition and injecta for curing avian toxoplasmosis, and preparation method thereof |
| CN101991587A (en) * | 2010-12-08 | 2011-03-30 | 纽素乐必佳（天津）药业集团有限公司 | Compound sulfadiazine injection and preparation method thereof |
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|---|---|---|---|---|
| WO2002074242A2 (en) * | 2001-03-16 | 2002-09-26 | Tyler Curiel | Inhibition of toxoplasma gondii) replication by pyridinylimidazoles |
| CN101450055A (en) * | 2007-11-29 | 2009-06-10 | 天津瑞普生物技术集团有限公司 | Soluble powder for treating livestock and poultry bacterial infection and parasitic disease |
| CN101816663A (en) * | 2009-02-26 | 2010-09-01 | 河南惠通天下动物药业有限公司 | Medicinal composition and injecta for curing avian toxoplasmosis, and preparation method thereof |
| CN101991587A (en) * | 2010-12-08 | 2011-03-30 | 纽素乐必佳（天津）药业集团有限公司 | Compound sulfadiazine injection and preparation method thereof |
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