CN1323713C - Novel usage of soluble P-lectin and anthrax lethal toxin - Google Patents
Novel usage of soluble P-lectin and anthrax lethal toxin Download PDFInfo
- Publication number
- CN1323713C CN1323713C CNB031465463A CN03146546A CN1323713C CN 1323713 C CN1323713 C CN 1323713C CN B031465463 A CNB031465463 A CN B031465463A CN 03146546 A CN03146546 A CN 03146546A CN 1323713 C CN1323713 C CN 1323713C
- Authority
- CN
- China
- Prior art keywords
- selectin
- palatelet
- solubility
- lethal toxin
- anthrax lethal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to an application of soluble P-lectine for preparing medicament for treating diseases of whole body haemorrhage, and provides an application of an anthracnose lethiferous toxin for preparing medicament for treating antithrombotic diseases.
Description
Technical field
The present invention relates to soluble platelet-selection, plain (palatelet-selectin, platelet-selectin P-selectin) are used for the treatment of the novel use of general hemorrhagic disease.
Background technology
The kind of hemorrhage very variation and its pathogenesis is quite complicated, for example blood vessel wall or connective tissue textural anomaly, and platelet amount or dysfunction, thrombin is unusual, and fibrinolysis excessively reaches CAC matter or the like., based on heredity whether hemorrhage can be categorized as heritability and nongenetic hemorrhagic disease.Heritability hemorrhagic disease such as hemophilia are because thrombin is undergone mutation, and make the blood coagulation Disability or lower institute to cause.At hemorrhage clinical case, then major part is the nongenetic hemorrhagic disease, hemorrhage, intestines and stomach ulcerative hemorrhage, the infectious disease that comprise that internal and external wound is hemorrhage, nutrition or vitamin K picked-up are not enough to be caused caused hemorrhage, that medical act caused was hemorrhage, women's production process hemorrhage, that hemopoietic system is not normal, liver function imbalance, autoimmune disease cause is hemorrhage, dengue hemorrhagic fever, the attack of hemorrhagic snake venom, anthrax, bacteremia and cancer cause is hemorrhage or the like.
Except that wound was hemorrhage, present therapy was all felt simply helpless for a large amount of generals are hemorrhage.Present known blood coagulation promotes medicament (as the fibrinolysis agent) to be only applicable to treat local hemorrhage.These blood coagulations promote medicament to enter in the body will form [rapidly, often cause the side effect of myocardial infarction and apoplexy.Therefore, the general hemostasis medication that there is no suitable safety at present and have no side effect.
One of plain family member selects in palatelet-selectin system, and it is positioned at the WP corpusculum (Weibel-Palade bodies) of hematoblastic α-granule and endotheliocyte.After endotheliocyte is subjected to the stimulation of thrombin or histamine, but the quick performance palatelet-selectin.(the solubility palatelet-selectin sP-selectin) can be found in the blood plasma soluble form of palatelet-selectin, is blood circulation protein.Solubility palatelet-selectin molecule exists with monomeric form in blood than the little 3kDa of palatelet-selectin molecule, then is to exist with oligomeric state with membrane-bound palatelet-selectin.Healthy people's solubility palatelet-selectin system from be found in endotheliocyte and hematoblastic selectivity shear pattern (Johnston, people such as G.I., 1990, J.Biol.Chem.265,21381-21385).
Existing research thinks that the plasma volume of solubility palatelet-selectin can be considered the useful tool (Smith that the expection thrombosis consumes blood platelet disorder (thrombotic consumptive platelet disorder), A. wait the people, 1999, Throm.Haemost.82,1593-1599).Blann, A.D. and Lip.G.Y. point out that then the solubility palatelet-selectin is circulated in the biological function of blood and unclear (J.Clin.Endocrinol.Metab. (2000) 85,1745-1747).Experiment of spent time of blood plasma agglutination (Plasma clotting time) is measured in the follow-up study utilization, (people such as Patrick Andre, 2000, the PNAS vol.97 of solidifying that can promote blood in the mouse body squeezed into the solubility palatelet-selectin in discovery, No.25,13835-13840).This research only just the branch handset change and locality is hemorrhage is described, and inference solubility palatelet-selectin may be relevant with the blood coagulation pathological changes.Yet this research does not point out that the solubility palatelet-selectin can be used for the treatment of general hemorrhagic disease.
Further acute myocardial infarction (AMI) patient and unstable angina patient's plasma soluble palatelet-selectin amount obviously raise (people such as Meral Kayikcioglu, Int JCardiol 2001,79:223 are then pointed out in research; People such as Enver Atalar, Int J Cardiol, 2001,78:69).Yet, the suggestion of the also not mentioned any relevant general hemorrhagic disease treatment of these documents.
In sum, there is no any document illustration or suggestion palatelet-selectin in the novel application of treatment general hemorrhagic disease.
Summary of the invention
The invention provides of the application of a kind of solubility palatelet-selectin in preparation treatment general hemorrhagic disease medicine.
The present invention also provides a kind of anthrax lethal toxin in the application of making treatment antithrombotic disease medicament.
The present invention relates to the application of solubility palatelet-selectin in the medicine of preparation treatment general hemorrhagic disease.
Described solubility palatelet-selectin is selected from: naturally occurring solubility palatelet-selectin, its genetic engineering recombinant, pleomorphism (polymorphic) variant, antithesis (allelic) variant and other isomer.
Described solubility palatelet-selectin is selected from: naturally occurring solubility palatelet-selectin and genetic engineering recombinant thereof.
But described solubility palatelet-selectin oral administration or intravenous injection medication.
The dosage of described solubility palatelet-selectin is that per kilogram of body weight answers about 0.1 milligamma of medication to about 100 milligrams.
Described general hemorrhagic disease is selected from dengue hemorrhagic fever, hemorrhagic snake venom and anthrax.
Described general hemorrhagic disease is the hemorrhage patient's condition in the bacteremia.
The present invention relates to the anthrax lethal toxin in the application of making treatment antithrombotic disease medicament.
Described anthrax lethal toxin is selected from: naturally occurring anthrax lethal toxin, its genetic engineering recombinant, pleomorphism (polymorphic) variant, antithesis (allelic) variant and other isomer.
Described anthrax lethal toxin is selected from: naturally occurring anthrax lethal toxin and genetic engineering recombinant thereof.
But described anthrax lethal toxin oral administration or intravenous injection medication.
The dosage of described anthrax lethal toxin is that per kilogram of body weight answers about 0.1 milligamma of medication to about 100 milligrams.
Described antithrombotic disease is selected from heart disease and apoplexy.
According to the present invention, the solubility palatelet-selectin provides the novel application of treatment general hemorrhagic disease.Inexpectancy of the present invention ground finds that the solubility palatelet-selectin has the function of obvious promotion blood coagulation, but can't cause thrombosis, causes myocardial infarction and apoplexy.Therefore, solubility palatelet-selectin of the present invention has good result and does not have bad side effect at treatment general hemorrhagic disease.
Description of drawings
Fig. 1 is the data of blood plasma agglutination result of the test; Horizontal stripe among the figure is representative respectively from top to bottom: control group immunoglobulin (IgG), anthrax toxin (LeTx), recombinant soluble palatelet-selectin (rP-sel), recombinant soluble palatelet-selectin (rP-sel)+anti-palatelet-selectin antibody (anti--P-sel), the anti-dengue virus first non-structural protein antibody (anti--NS1 antibody)+palatelet-selectin and the anti-dengue virus first non-structural protein antibody (anti--NS1 antibody).
Fig. 2 is the data of mice protection result of the test; Fig. 2 A is the protection data of solubility palatelet-selectin to injection hemorrhagic snake venom mice, the western western diamond rattlesnake snake venom of--zero--among the figure-representative+recombinant soluble palatelet-selectin (rP-sel),--represent east western diamond rattlesnake snake venom+recombinant soluble palatelet-selectin (rP-sel), the western western diamond rattlesnake snake venom of--representative ,-■-represent east western diamond rattlesnake snake venom; Fig. 2 B is for being the protection data of solubility palatelet-selectin to injection anthrax toxin mice;-●-represent anthrax toxin (LeTx);--zero---represent anthrax toxin (LeTx)+recombinant soluble palatelet-selectin (rP-sel) ,--represent anthrax toxin (LeTx)+control group immunoglobulin (IgG) and--represent anthrax toxin (LeTx)+recombinant soluble palatelet-selectin (rP-sel)+anti-palatelet-selectin antibody (resist-P-sel).
Fig. 3 is the result of mouse platelets coagulation time test; Wherein AA represents arachidonic acid; And LeTx represents anthrax toxin.
The specific embodiment
At the general hemorrhage, still there is not effectively and can not causes at present the medicine of thrombosis risk.Existing Therapeutic Method only is supportive (supporting) treatment mostly, and there is no preferred approach, can to treat general hemorrhage.The invention provides the novel use of solubility palatelet-selectin treatment general hemorrhagic disease.This solubility palatelet-selectin can effectively be treated hemorrhage, particularly as anthrax and dengue hemorrhagic fever, and can not cause thrombotic side effect.In addition, solubility palatelet-selectin of the present invention also can be used for treating the hemorrhage patient's condition that bacteremia causes.
The novel use of solubility palatelet-selectin
The invention provides of the application of a kind of solubility palatelet-selectin in preparation treatment general hemorrhagic disease medicine.
Solubility palatelet-selectin and medical composition thereof
According to the present invention, term " the solubility palatelet-selectin " comprise soluble form and genetic engineering recombinant or pleomorphism (polymorphic) or antithesis (allelic) variant or other isomer (isoform) of naturally occurring palatelet-selectin.This term also comprises the solubility palatelet-selectin of modification and unmodified, reaches not candy base form as the candy baseization.Studies show that the solubility palatelet-selectin can be from activatory platelet or endotheliocyte.Yet, general skill personage for the function of solubility palatelet-selectin and and platelet between relation very not clear.Inexpectancy ground, the present invention finds that the solubility palatelet-selectin has quite good effect in the treatment of general hemorrhagic disease.According to the present invention, any type of solubility palatelet-selectin that is fit to treatment general hemorrhagic disease all can be used for the present invention.Preferably, solubility palatelet-selectin of the present invention is the recombinant of naturally occurring solubility palatelet-selectin or solubility palatelet-selectin.The present invention is according to the present invention, and the solubility palatelet-selectin is that general skill personage can be easy to the winner, for example separates from natural origin, and is synthetic available from commercial source or chemosynthesis or mat Protocols in Molecular Biology.
Solubility palatelet-selectin of the present invention can be prepared into medical composition with pharmaceutically acceptable supporting agent.Except that solubility palatelet-selectin and supporting agent, said composition can contain diluent in addition, filler, salt, buffer agent, tranquilizer, known substances in lytic agent and other this skill.Term " pharmaceutically acceptable " mean not the avirulence material of biological action that can the interferon activity composition.The characteristic system that is used for the supporting agent of solubility palatelet-selectin medical composition of the present invention decides according to the medication route.Medical composition of the present invention also can contain known Procoagulants in this skill, for example vitamin K and fibrinolysis agent.
The medication of solubility palatelet-selectin
For implementing application of the present invention, but the solubility palatelet-selectin of the present invention of effective dose or medical composition medication comprise the mankind and non-human mammal to the mammal that suffers from hemorrhage in the treatment.According to the present invention, but the various general fashions of medication mat of solubility palatelet-selectin of the present invention or medical composition carry out, as intravenous injection.When with the liquid form medication, can add liquid carrier, as water, physiology salt solution or vegetable and animals oils.The medical composition of this liquid form comprises 0.5% to 90% by weight solubility palatelet-selectin, is preferably 1% to 50% by weight solubility palatelet-selectin.
When the solubility palatelet-selectin of effective dose was gone up in intravenous injection medication treatment, the solubility palatelet-selectin was non-through the acceptable aqueous solution form of intestinal.Preparing this kind, non-can to accept pH, isotonia, stability and conditions of similarity that solution need consider through intestinal be knownly in this skill to know examination or technology.Except that the solubility palatelet-selectin, preferable intravenous injection medical composition can contain in this skill known grade and open mediator.Medical composition of the present invention also can contain tranquilizer, preservative agent, buffer agent, antioxidant or other general skill personage's known additives.Use the time system of the intravenous injection treatment of the present composition to decide on the patient's condition of desire treatment disease seriousness and sufferer out of the ordinary.The doctor will determine to use the suitable intravenous administration time of medical composition of the present invention.
The character of the previous treatment that the amount system of solubility palatelet-selectin of the present invention in medical composition carried out according to the character of the desire treatment patient's condition and seriousness and sufferer and deciding.The doctor will determine the amount of solubility palatelet-selectin with the situation of indivedual sufferers.At the various medical compositions that are used to implement purposes of the present invention, the expection per kilogram of body weight answers about 0.1 milligamma of medication to about 100 milligrams solubility palatelet-selectin.
Particularly, solubility palatelet-selectin of the present invention can be used for treating dengue hemorrhagic fever, hemorrhagic snake venom and anthrax and can treat the hemorrhage patient's condition in the bacteremia.Preferably, solubility palatelet-selectin of the present invention can be used for treating dengue hemorrhagic fever, hemorrhagic snake venom and anthrax.Dengue hemorrhagic fever system repeatedly infects the hemorrhage patient's condition of general that is produced behind the dengue fever.When infecting dengue fever for the first time, have only cold symptoms not have life danger mostly.Yet, after repeatedly infecting dengue virus, have the hemorrhage patient's condition of general that a certain proportion of patient produces fatal risk.(dengue non-structural protein 1 NS1) can induce host's autoimmune production of antibodies to first non-structural protein of dengue virus, and it is tired and will increase because repeatedly infect dengue fever.These autoimmune antibody can cause blood coagulation speed slack-off and produce the vascular lesion of possible other.The hemorrhagic venom is the common open air injury in Taiwan and other torrid areas, and unique effective therapeutic modality is the injection antivenin.Yet poisonous snake is of a great variety, is the treatment ophidism, must prepare specific antivenin at each Serpentis; This is the burdens that are difficult for reaching for remote districts.Anthrax then is that anthrax bacillus (Bacillus anthracis) infects caused disease, and the lethal toxin that anthrax bacillus produced (anthrax lethal toxin) is main virulence factor (virulence factor).Find in the anthrax death cases that the dead all has a large amount of internal hemorrhages.The present invention finds that surprisingly the solubility palatelet-selectin has excellent curative for dengue hemorrhagic fever, hemorrhagic snake venom and anthrax, and does not cause any side effect.
The novel use of anthrax lethal toxin
The present invention provides a kind of anthrax lethal toxin in the application of making treatment antithrombotic disease medicament in addition.Thrombus disease may cause complication such as myocardial infarction and apoplexy, and the cardiovascular disease that these thromboembolism caused almost comes out at the top in ten big cause of death ranking lists of developed countries.Antithrombotic reagent commonly used comprises platelet suppressant drug, the molten former activation factor of tectotype fibrin (tPA), urokinase (uPA) and streptomycete kinases (SK) etc.Yet, still lack very effective antithrombotic reagent at present.The present invention finds that surprisingly the anthrax lethal toxin can effectively suppress platelet aggregation, can be used as the medicine of treatment antithrombotic disease by this.
According to the present invention, term " the anthrax lethal toxin " comprise naturally occurring anthrax lethal toxin and genetic engineering recombinant or pleomorphism (polymorphic) or antithesis (allelic) variant or other isomer (isoform).According to the present invention, any type of anthrax lethal toxin that is fit to treatment antithrombotic disease all can be used for the present invention.Preferably, anthrax lethal toxin of the present invention is the recombinant of naturally occurring anthrax lethal toxin or anthrax lethal toxin.The present invention is according to the present invention, and the anthrax lethal toxin is that general skill personage can be easy to the winner, for example separates from natural origin, and is synthetic available from commercial source or chemosynthesis or mat Protocols in Molecular Biology.
According to the present invention, but the anthrax lethal toxin of the present invention of effective dose or medical composition medication comprise the mankind and non-human mammal to the mammal that suffers from the antithrombotic disease in the treatment.According to the present invention, but the various general fashions of medication mat of anthrax lethal toxin of the present invention or medical composition carry out, as oral or intravenous injection; Be preferably the intravenous medication.Preferably, effective dosage of anthrax lethal toxin of the present invention is contemplated to per kilogram of body weight and answers extremely about 100 milligrams of about 0.1 milligammas of medication.
Anthrax lethal toxin of the present invention can significantly suppress hematoblastic coagulation, and reduces the risk of complication such as producing myocardial infarction and apoplexy.
Embodiment
The blood plasma agglutination test of example 1 dengue hemorrhagic fever and anthrax toxin
Blood plasma agglutination experiment system with the blood of mice C57BL/6J centrifugal 25 minutes of the condition of 1,500 * g to obtain mice " blood plasma of aleukia (platelet-poor plasma, PPP) ".Gained blood plasma is added not ear concentration calcium chloride (CaCl of equal-volume 20 millis
2) after, 800rpm and 37 ℃, with CA instrument (aggregometer:model 600B, Ion-Trace, Stouffville, Canada) variation of its light absorption value that causes because of coagulation of meter record and record agglutinate time of blood plasma (plasma clotting time).
This example uses following reagent to carry out the blood plasma agglutination test: reorganization palatelet-selectin-Ig Fc albumen is (available from R ﹠amp; D Systems Inc., Minneapolis, Minnesota USA) originates as palatelet-selectin.Dengue virus albumen then uses dengue virus first non-structural protein, it is from first nonstructural protein gene that duplicates synthetic dengue virus second type (dengue virus type II) native country, Taiwan separated strain (PL046) with round pcr (people such as Chang, 2002, J Infect Dis 186,743-51).Anthrax toxin system uses the recombinant anthrax lethal toxin, it is to derive from DNA and protein data (U.S. NCBI Gene Bank in U.S.'s gene bank data, AF065404 andNC_001496) with the synthetic gene technology in conjunction with the synthetic DNA of round pcr (people such as Chang, 1993, Biochem Biophys Res Cornmun 190,242-9).
To after the anti-dengue virus first non-structural protein antibody (anti-dengue non-structureprotein NS1 antibody) and anthrax toxin (LeTx) injection are in the mice body, can cause the inhibition blood plasma agglutination.As shown in Figure 1, will resist-NS1 antibody and LeTx carry out the vein injection after 24 hours, and agglutinate time of blood plasma significantly increases, and shows that coagulation speed descends.Opposite, recombinant soluble palatelet-selectin (rP-sel) was carried out the vein injection after 24 hours, the mouse agglutinate time of blood plasma significantly reduces, and shows that coagulation speeds up.But as add anti-palatelet-selectin antibody (anti--P-sel) after, the effect of above-mentioned rP-sel can be neutralized.In addition, will resist-NS1 antibody and solubility palatelet-selectin carry out the vein injection after 24 hours together, compared to injection anti--NS1 antibody, agglutinate time of blood plasma significantly reduces.
By the result of above-mentioned Fig. 1 as can be known, the solubility palatelet-selectin can promote the activation of body intravascular coagulation mechanism, and the solubility P of injection therapeutic dosage selects the plain injury that can't cause laboratory animal separately, but can significantly promote blood coagulation efficient.Therefore, the solubility palatelet-selectin is that a very potential general hemostasis medication is selected.
The mice protection test of example 2 anthrax toxins and hemorrhagic snake venom
In the protection test of palatelet-selectin, with mice elder generation injection reorganization palatelet-selectin-Ig albumen to mice.Back 4 hours of palatelet-selectin interpolation neutrality monoclonal antibody or matched group human immunoglobulin IgG (dosage is 1.2 gram/grams) are again with vein injection anthrax toxin and hemorrhagic snake venom.Then observe mouse diing time.The source of reorganization palatelet-selectin-Ig albumen and anthrax toxin is shown in example 1.The venom of hemorrhagic snake venom system use western western diamond rattlesnake (Crotalus atrox) and east western diamond rattlesnake (Crotalus adamanteus) (available from Sigma, St.Louis, MissouriUSA).
Shown in Fig. 2 A, behind the venom of western western diamond rattlesnake (Crotalus atrox) of injection and east western diamond rattlesnake (Crotalus adamanteus), respectively cause six mices (C57BL/6J) dead in 1 hour totally.Yet in advance the mice of injection recombinant soluble palatelet-selectin survive above three months totally, proved that the solubility palatelet-selectin has a protective capability to hemorrhage.On open evidence hemorrhagic snake venom venom injury can break away from dead threat (Fig. 2 A) via the treatment of solubility palatelet-selectin.Therefore, the solubility palatelet-selectin might be developed becomes the medication of the hemorrhage of single broad-spectrum snake venom.
Shown in Fig. 2 B, injection anthrax toxin (LeTx) causes six mices (C57BL/6J) dead in day in 4-5 totally.Yet the mice of injection recombinant soluble palatelet-selectin has one to die from the 8th day in advance, dies from the 18th day for one, then survives above three months for all the other four.Go up this digital proof solubility palatelet-selectin and have a protective capability hemorrhage.In addition, the protective capability that provided of this solubility palatelet-selectin can be neutralized by the narrow spectrum antibody of palatelet-selectin as seen from the figure.Therefore, open test explanation solubility palatelet-selectin on and can reduce the death that the anthrax lethal toxin causes.
Example 3 bacteremic mice protection tests
The reagent of mice protection test and method are shown in example 2.Emulation bacteremia in the blood plasma of mice (C57BL/6J) is beaten with the escherichia coli liquid application of 1 * 108 bacterium number/gram by mice bacteremia system.As shown in table 1,6 mices of injection escherichia coli liquid are total dead in 24 hours.Yet, the average many survivals of the mice of injection recombinant soluble palatelet-selectin in advance 2 days.Therefore, the solubility palatelet-selectin is to the true tool protection of bacteremia mice effect.
Table 1
| The mice processing mode | Average survival natural law |
| Injection solubility palatelet-selectin | Above 90 days |
| Injection escherichia coli liquid | 1 day |
| Injection escherichia coli liquid+solubility palatelet- | 3 days |
The inhibition platelet aggregation test of example 4 anthrax lethal toxins
The anthrax lethal toxin is tested with platelet aggregation test the effect system of anticoagulant.Anthrax toxin system uses the recombinant anthrax lethal toxin, it is to derive from DNA and protein data (U.S. NCBI Gene Bank in U.S.'s gene bank data, AF065404 and NC_001496) with the synthetic gene technology in conjunction with the synthetic DNA of round pcr (people such as Chang, 1993, BiochemBiophys Res Commun 190,242-9).
Take the blood of mice (C57BL/6J), and under the condition of 500 * g, obtained to be rich in centrifugal 10 minutes hematoblastic blood plasma (platelet-rich plasma, PRP).Gained blood plasma is added platelet activating agent arachidonic acid (arachidonic acid), stirring under the condition of (800rpm) and 37 ℃ with CA instrument (aggregometer:model 600B, Ion-Trace, Stouffville, Canada) variation of its light absorption value that causes because of coagulation of meter record and record the platelet aggregation time (platelet aggregation time).As shown in Figure 3, after the platelet activator was handled, the platelet of purification was carried out normal agglutination.Yet inhibitory reaction appears in the experimental group that adds the anthrax lethal toxin.Therefore, the anthrax lethal toxin can significantly suppress platelet aggregation.
Claims (6)
1. the application of anthrax lethal toxin in making treatment antithrombotic disease medicament.
2. application according to claim 1 is characterized in that described anthrax lethal toxin is selected from: naturally occurring anthrax lethal toxin, its genetic engineering recombinant, pleomorphism (polymorphic) variant, antithesis (allelic) variant and other isomer.
3. application according to claim 1 is characterized in that described anthrax lethal toxin is selected from: naturally occurring anthrax lethal toxin and genetic engineering recombinant thereof.
4. application according to claim 1, but it is characterized in that described anthrax lethal toxin oral administration or intravenous injection medication.
5. application according to claim 1, the dosage that it is characterized in that described anthrax lethal toxin are that per kilogram of body weight answers about 0.1 milligamma of medication to about 100 milligrams.
6. application according to claim 1 is characterized in that described antithrombotic disease is selected from heart disease and apoplexy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031465463A CN1323713C (en) | 2003-07-07 | 2003-07-07 | Novel usage of soluble P-lectin and anthrax lethal toxin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031465463A CN1323713C (en) | 2003-07-07 | 2003-07-07 | Novel usage of soluble P-lectin and anthrax lethal toxin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1565619A CN1565619A (en) | 2005-01-19 |
| CN1323713C true CN1323713C (en) | 2007-07-04 |
Family
ID=34471770
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031465463A Expired - Fee Related CN1323713C (en) | 2003-07-07 | 2003-07-07 | Novel usage of soluble P-lectin and anthrax lethal toxin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1323713C (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1174575A (en) * | 1994-11-30 | 1998-02-25 | 味之素株式会社 | Antithrombotic agent and anti-von willebrand factor monoclonal antibodies |
-
2003
- 2003-07-07 CN CNB031465463A patent/CN1323713C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1174575A (en) * | 1994-11-30 | 1998-02-25 | 味之素株式会社 | Antithrombotic agent and anti-von willebrand factor monoclonal antibodies |
Non-Patent Citations (3)
| Title |
|---|
| 以毒攻毒，炭疽VS癌症 黄楠，学术论坛，第2期 2002 * |
| 炭疽毒素及其细胞受体的研究进展 李艳玲 等，中国生物化学与分子生物学报，第18卷第6期 2002 * |
| 炭疽毒素及其细胞受体的研究进展 李艳玲 等，中国生物化学与分子生物学报，第18卷第6期 2002;以毒攻毒，炭疽VS癌症 黄楠，学术论坛，第2期 2002 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1565619A (en) | 2005-01-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1107521C (en) | Method for reducing the viscosity of pathological mucoid airway contents in the respiratoy tract | |
| Girolami et al. | A ‘new’congenital haemorrhagic condition due to the presence of an abnormal factor X (factor X Friuli): study of a large kindred | |
| Sorimachi et al. | Activation of macrophages by lactoferrin: secretion of TNF‐α, IL‐8 and NO | |
| CN1056154C (en) | Method of producing reconstituted lipoproteins | |
| Hutton et al. | Arboreal green pit vipers (genus Trimeresurus) of South-East Asia: bites by T. albolabris and T. macrops in Thailand and a review of the literature | |
| CN107405391B (en) | Systemic and topical application of platelet microparticles to treat bleeding in trauma patients | |
| Glenchur et al. | Macroglobulinemia: report of two cases | |
| US20060039991A1 (en) | Biological tissue regenerative agent and method for preparing and using same | |
| Arasu et al. | Coagulation profile, gene expression and bioinformatics characterization of coagulation factor X of striped murrel Channa striatus | |
| Basler et al. | Ulcerative colitis and the skin | |
| EP4219534A2 (en) | Methods for treatment of and prophylaxis against inflammatory disorders | |
| McCreary et al. | Poisonous snake bites: Report of a case | |
| CN1323713C (en) | Novel usage of soluble P-lectin and anthrax lethal toxin | |
| Leonel et al. | Bothrops jararaca snake venom inflammation induced in human whole blood: role of the complement system | |
| JPS62255430A (en) | Treatment for mammalian vas disease | |
| JPS59227827A (en) | Chain-relating antigen originated from plasmodium, and its preparation | |
| Torrey et al. | Malignant mastocytosis with circulating mast cells | |
| CN101880656B (en) | Agkistrodon halys venom thrombin and preparation method and application thereof | |
| Yogev | A humoral solution: Autologous blood products and tissue repair | |
| Martins et al. | Polianna Lemos Moura Moreira Albuquerque [, Louise Donadello Tessarolo [3], Fernanda Holanda Menezes [4], Thayanne Barreto de Lima [4], José Hícaro Hellano Gonçalves Lima Paiva [5], Geraldo Bezerra da Silva Júnior [6] | |
| Ruwanpathirana et al. | Clinical characteristics and outcomes of pulmonary haemorrhage in leptospirosis: A retrospective cohort study from Sri Lanka | |
| Myhre | Gram-positive endotoxemia and modulation of the innate immune response | |
| Rubio-Haro et al. | Diagnostic-therapeutic algorithm for thrombotic microangiopathy. A report of two cases | |
| Effiong et al. | Speed of capillary blood flow and d-dimer levels in sickle cell anaemia patients in Calabar, cross river state | |
| CN1426308A (en) | Utilization of ADAMTS-1 protein and method of screening aggrecanase activity regulator |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070704 Termination date: 20150707 |
|
| EXPY | Termination of patent right or utility model |