The applicant requires the U.S. Patent application No.10/353 with proposition on January 29th, 2003, and 48 is priority.
The specific embodiment
A kind of medicinal mixture and a kind of method for preparing this therapeutic composition, this therapeutic composition is blocking-up HIV-1 and/or the virus replication of HIV-2 in the CD4+ of human immunity system cell in all stages that HIV-1 and/or HIV-2 infect and acquired immune deficiency syndrome (AIDS), be used for the HIV treatment of the HIV sufferers of this treatment of needs, this therapeutic composition comprises allocryptopine, nimodipine, potassium iodide, potassium iodate, inuline, silver, zinc, chromium, orotic acid, the 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane with knock-down.In one embodiment of the invention, this medicinal mixture further comprises taraxasterol and the B-sitosterol with knock-down.
The invention still further relates to the method for a kind of preparation medicinal mixture of blocking-up HIV-1 and/or the virus replication of HIV-2 in the CD4+ of human immunity system cell in all stages of HIV-1 and/or HIV-2 viral infection and acquired immune deficiency syndrome (AIDS), it is characterized in that, at room temperature mix following compounds until obtaining a kind of almost uniform mixture: allocryptopine 1.0mg is to 10.0mg, nimodipine 20.0mg is to 100.0mg, potassium iodide 120.0mg is to 560.0mg, potassium iodate 30.0mg is to 140.0mg, inuline 125.0mg is to 375.0mg, silver 0.10mg is to 0.50mg, zinc 10.0mg is to 20.0mg, chromium 0.05mg is to 0.20mg, orotic acid 150.0mg is to 500.0mg, 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane 100.0mg is to 300.0mg, next, can be pressed into tablet, also can make a kind of tablet with coating, perhaps also can make wafer (wafer), suppository, effervescent powder, gel or colloid solution are perhaps made suspension, syrup, dissolve in the salt of body fluid or intramuscular injection or intravenous injection liquid, also can be contained in the ampoule bottle.
Existing relevant treatment be diagnosed as that HIV infects or the publication of the patient's of acquired immune deficiency syndrome (AIDS) (acquired immune deficiency syndrome (AIDS)) method in, all do not described anyly here, blocked the Drug therapy/pharmaceutical preparation of HIV-1 and/or the HIV-2 virus replication in the CD4+ of human immunity system cell based on the reasoning of being adopted.
Prerequisite of the present invention in this discussion is following reasoning, that is, the basis of HIV-1 and the HIV-2 virus replication in the CD4+ of human immunity system cell is to be that exeitono-excimeric is relevant between HIV-1 and HIV-2 virus and the CD4+ of the human immunity system cell.
Adopt the result of this reasoning as follows: the beginning that is intended to treat the therapy of HIV-1 and HIV-2 viral infection and acquired immune deficiency syndrome (AIDS) just be reduced to make the approach that duplicates of blocking HIV-1 and HIV-2 virus fully species distribution in the patient body.
It is helpful that following material has been proved finishing this task: allocryptopine, nimodipine, potassium iodide, potassium iodate, inuline, silver, zinc, chromium, orotic acid, 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane.Other material that helps to finish this task of having found has: taraxasterol and B-sitosterol.
Know, allocryptopine is a kind of nucleotide phosphodiesterase blocker, nimodipine is a kind of calcium channel blocker, under acid condition, unite and use potassium iodide and potassium iodate can produce the iodine free radical, inuline is a kind of polysaccharide of not degrading in vivo, silver, zinc and chromium are the elements that plays a role in the enzyme catalysis process, and 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane chelated iron ion, orotic acid are a kind of precursors of nucleotide compound.
Yet material listed above never occurred together in the past or used, and especially never used together in treatment for example described in the invention is used.
An object of the present invention is to provide a kind of medicinal mixture that is used for blocking HIV1 and HIV-2 virus replication in the CD4+ of the human immunity system cell.
The invention provides a kind of at HIV-1 and/or HIV-2 viral infection all stages and acquired immune deficiency syndrome (AIDS) in the medicinal mixture of blocking-up HIV-1 and/or the virus replication of HIV-2 in the CD4+ of human immunity system cell, known carrier and/or complementary material before it comprises, and active substance, it is characterized in that containing at least 10 kinds of chemical substances as active substance, wherein:
The content of-allocryptopine be 1.0mg to 10.0mg,
The content of-nimodipine be 20.0mg to 100.0mg,
The content of-potassium iodide be 120.0mg to 560.0mg,
The content of-potassium iodate is 30.0mg to 140.0mg,
The content of-inuline be 125.0mg to 375.0mg,
The content of-Yin be 0.10mg to 0.50mg,
The content of-zinc be 10.0mg to 20.0mg,
The content of-chromium be 0.05mg to 0.20mg,
The content of-orotic acid be 150.0mg to 500.0mg,
The content of-1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is that 100.0mg is to 300.0mg.
Following proportioning helps achieving the goal:
The content of allocryptopine is 10.0mg, the content of nimodipine is 100.0mg, the content of potassium iodide is 560.0mg, the content of potassium iodate is 140.0mg, and the content of inuline is 375.0mg, and the content of silver is 0.50mg, the content of zinc is 20.0mg, the content of chromium is 0.20mg, and the content of orotic acid is 500.0mg, and the content of 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is 300.0mg.
Be preferably as follows proportioning:
The content of allocryptopine is 4.50mg, the content of nimodipine is 60.0mg, the content of potassium iodide is 340.0mg, the content of potassium iodate is 85.0mg, and the content of inuline is 250.0mg, and the content of silver is 0.30mg, the content of zinc is 15.0mg, the content of chromium is 0.125mg, and the content of orotic acid is 325.0mg, and the content of 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is 200.0mg.
Be preferably as follows proportioning:
The content of allocryptopine is 4.50mg, the content of nimodipine is 60.0mg, and the content of potassium iodide is 340.0mg, and the content of potassium iodate is 85.0mg, the content of inuline is 250.0mg, the content of silver is 0.30mg, and the content of zinc is 15.0mg, and the content of chromium is 0.125mg, the content of orotic acid is 325.0mg, the content of 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is 200.0mg, and the content of taraxasterol is 350mg, and the content of B-sitosterol is 400mg.
Be preferably as follows proportioning:
The content of allocryptopine is 1.0mg, the content of nimodipine is 20.0mg, and the content of potassium iodide is 120.0mg, and the content of potassium iodate is 30.0mg, the content of inuline is 125.0mg, the content of silver is 0.10mg, and the content of zinc is 10.0mg, and the content of chromium is 0.05mg, the content of orotic acid is 250.0mg, the content of 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is 100.0mg, and the content of taraxasterol is 250mg, and the content of B-sitosterol is 300mg.
Be preferably as follows proportioning:
The content of allocryptopine is 1.0mg, the content of nimodipine is 20.0mg, the content of potassium iodide is 120.0mg, the content of potassium iodate is 30.0mg, and the content of inuline is 125.0mg, and the content of silver is 0.10mg, the content of zinc is 10.0mg, the content of chromium is 0.05mg, and the content of orotic acid is 250.0mg, and the content of 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is 100.0mg
Preferred allocryptopine: nimodipine: potassium iodide: potassium iodate: inuline: silver: zinc: chromium: orotic acid: 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane in weight ratio, remained on 1: 20: 120: 30: 125: 0.1: 10: 0.05: 250: 100.
The mixture of these compositions is preferably tablet, has the tablet of coating, wafer, suppository, effervescent powder, gel or colloid solution.
These mixture of ingredients are preferably suspension, syrup or dissolve in the salt of body fluid, intramuscular injection liquid or intravenous injection liquid.
The method of a kind of preparation medicinal mixture of blocking-up HIV-1 and/or the virus replication of HIV-2 in the CD4+ of human immunity system cell in all stages of HIV-1 and/or HIV-2 viral infection and acquired immune deficiency syndrome (AIDS), it is characterized in that, at room temperature mix following ingredients to obtaining the homogeneous mixture:
The content of-allocryptopine be 1.0mg to 10.0mg,
The content of-nimodipine be 20.0mg to 100.0mg,
The content of-potassium iodide be 120.0mg to 560.0mg,
The content of-potassium iodate is 30.0mg to 140.0mg,
The content of-inuline be 125.0mg to 375.0mg,
The content of-Yin be 0.10mg to 0.50mg,
The content of-zinc be 10.0mg to 20.0mg,
The content of-chromium be 0.05mg to 0.20mg,
The content of-orotic acid be 150.0mg to 500.0mg,
The content of-1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is that 100.0mg is to 300.0mg.
Be preferably as follows proportioning:
The content of allocryptopine is 10.0mg, the content of nimodipine is 100.0mg, the content of potassium iodide is 560.0mg, the content of potassium iodate is 140.0mg, and the content of inuline is 375.0mg, and the content of silver is 0.50mg, the content of zinc is 20.0mg, the content of chromium is 0.20mg, and the content of orotic acid is 500.0mg, and the content of 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is 300.0mg.
Be preferably as follows proportioning:
The content of allocryptopine is 4.50mg, the content of nimodipine is 60.0mg, the content of potassium iodide is 340.0mg, the content of potassium iodate is 85.0mg, and the content of inuline is 250.0mg, and the content of silver is 0.30mg, the content of zinc is 15.0mg, the content of chromium is 0.125mg, and the content of orotic acid is 325.0mg, and the content of 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is 200.0mg.
Be preferably as follows proportioning:
The content of allocryptopine is 1.0mg, the content of nimodipine is 20.0mg, the content of potassium iodide is 120.0mg, the content of potassium iodate is 30.0mg, and the content of inuline is 125.0mg, and the content of silver is 0.10mg, the content of zinc is 10.0mg, the content of chromium is 0.05mg, and the content of orotic acid is 250.0mg, and the content of 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane is 100.0mg.
Preferred allocryptopine: nimodipine: potassium iodide: potassium iodate: inuline: silver: zinc: chromium: orotic acid: 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane by quality ratio, remained on 1: 20: 120: 30: 125: 0.1: 10: 0.05: 250: 100.
The method of said medicine mixture and this medicinal mixture of preparation can further comprise taraxasterol and the B-sitosterol with knock-down.Preferred said medicine mixture and preparation method thereof is characterised in that, at room temperature following material is mixed until the mixture that obtains a kind of almost homogeneous: allocryptopine 1.0mg is to 10.0mg, nimodipine 20.0mg is to 100.0mg, potassium iodide 120.0mg is to 560.0mg, potassium iodate 30.0mg to 140.0mg, inuline 125.0mg is to 375.0mg, silver 0.10mg is to 0.50mg, zinc 10.0mg is to 20.0mg, chromium 0.05mg is to 0.20mg, orotic acid 150.0mg is to 500.0mg, 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane, 100.0mg to 300.0mg, taraxasterol 250mg is to 400mg, with B-sitosterol 300mg to 500mg, next, can be pressed into tablet, also can make tablet with coating, perhaps also can make wafer, suppository, effervescent powder, gel or colloid solution, perhaps make suspension, syrup, dissolve in body fluid, intramuscular injection liquid, or the salt of intravenous injection liquid, also can be contained in the ampoule bottle.
Preferred allocryptopine: nimodipine: potassium iodide: potassium iodate: inuline: silver: zinc: chromium: orotic acid: 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane: taraxasterol: the B-sitosterol in weight ratio, remained on 1: 20: 120: 30: 125; 0.1: 10: 0.05: 250: 100: 400: 500.
Preferred allocryptopine: nimodipine: potassium iodide: potassium iodate: inuline: silver: zinc: chromium: orotic acid: 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane: taraxasterol: B-sitosterol, in weight ratio, remained on 1: 20: 120: 30: 125: 0.1: 10: 0.05: 250: 100: 350: 400.
These mixture of ingredients are preferably tablet, have the tablet of coating, wafer, suppository, effervescent powder, gel, perhaps colloid solution.
These mixture of ingredients are preferably suspension, syrup or dissolve in the salt of body fluid, intramuscular injection liquid or intravenous injection liquid.
The favourable function of the medicinal mixture among the present invention is the approach of receptors bind on gp160 albumen and the CD4+ of the human immunity system cell of blocking-up HIV capsule, and the while has also been blocked the cell internal procedure relevant with the HIV-2 virus replication with HIV-1.
Example 1: the composition of medicinal mixture:
Allocryptopine 10.0mg, nimodipine 100.0mg, potassium iodide 560.0mg, potassium iodate 140.0mg, inuline 375.0mg, silver-colored 0.50mg, zinc 20.0mg, chromium 0.20mg, orotic acid 500.0mg, 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane 300.0mg.
The preparation of medicinal mixture:
Following material is at room temperature mixed: 10.0mg allocryptopine, 100.0mg nimodipine, 560.0mg potassium iodide, 140.0mg potassium iodate, 375.0mg inuline, 0.50mg silver, 20.0mg zinc, 0.20mg chromium, 500.0mg orotic acid, 300.0mg 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane.
After adding all the components, they are mixed together 10-20 minute until becoming the homogeneous mixture.Next this mixture can be pressed into tablet, also can be the tablet with coating, perhaps wafer, suppository, effervescent powder, gel, perhaps colloid solution.
Example 2: the composition of medicinal mixture:
Allocryptopine 1.0mg, nimodipine 20.0mg, potassium iodide 120.0mg, potassium iodate 30.0mg, inuline 125.0mg, silver-colored 0.10mg, zinc 10.0mg, chromium 0.05mg, orotic acid 150.0mg, 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane 100.0mg.
The preparation of medicinal mixture:
Following material is at room temperature mixed: 1.0mg allocryptopine, 20.0mg nimodipine, 120.0mg potassium iodide, 30.0mg potassium iodate, 125.0mg inuline, 0.10mg silver, 10.0mg zinc, 0.05mg chromium, 150.0mg orotic acid, 100.0g 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane.
After adding all the components, they are mixed together 10-20 minute until becoming the homogeneous mixture.Next this mixture can be made into suspension, and syrup dissolves in the salt of body fluid or intramuscular injection liquid or intravenous injection liquid, also can be contained in the ampoule bottle.
Example 3: the composition of medicinal mixture:
Allocryptopine 10.0mg, nimodipine 100.0mg, potassium iodide 560.0mg, potassium iodate 140.0mg, inuline 375.0mg, silver-colored 0.50mg, zinc 20.0mg, chromium 0.20mg, orotic acid 500.0mg, 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane 300.0mg, taraxasterol 400mg, B-sitosterol 500mg.
The preparation of medicinal mixture:
Following material is at room temperature mixed: 10.0mg allocryptopine, 100.0mg nimodipine, 560.0mg potassium iodide, 140.0mg potassium iodate, 375.0mg inuline, 0.50mg silver, 20.0mg zinc, 0.20mg chromium, 500.0mg orotic acid, 300.0mg 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane, 400mg taraxasterol, 500mgB-sitosterol.
After adding all the components, they are mixed together 10-20 minute until becoming the homogeneous mixture.Next this mixture can be pressed into tablet, also can be the tablet with coating, perhaps wafer, suppository, effervescent powder, gel, perhaps colloid solution.
Example 4: the composition of medicinal mixture:
Allocryptopine 1.0mg, nimodipine 20.0mg, potassium iodide 120.0mg, potassium iodate 30.0mg, inuline 125.0mg, silver-colored 0.10mg, zinc 10.0mg, chromium 0.05mg, orotic acid 150.0mg, 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane 100.0mg, taraxasterol 250mg, B-sitosterol 300mg.
The preparation of medicinal mixture:
Following material is at room temperature mixed: 1.0mg allocryptopine, 20.0mg nimodipine, 120.0mg potassium iodide, 30.0mg potassium iodate, 125.0mg inuline, 0.10mg silver, 10.0mg zinc, 0.05mg chromium, 150.0mg orotic acid, 100.0mg 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane, 250mg taraxasterol, 300mgB-sitosterol.
After adding all the components, they are mixed together 10-20 minute until becoming the homogeneous mixture.Next this mixture can be made into suspension, and syrup dissolves in the salt of body fluid or intramuscular injection liquid or intravenous injection liquid, also can be contained in the ampoule bottle.
Term " has knock-down " and is meant the effective dose of Chinese medicine mixture of the present invention (mixture that comprises allocryptopine, nimodipine, potassium iodide, potassium iodate, inuline, silver, zinc, chromium, orotic acid, 1-amino-6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosane).The actual dose of medicinal mixture of the present invention for particular patient, composition and administering mode, can change to some extent to reach satisfied curative effect.Selected dosage depends on the activity of specific compound, route of administration, the patient's who is treated the state of an illness and health and former medication history.Yet from beginning progressively to improve dosage than reaching the low dosage of expectation curative effect required compound, until reaching desired effect, this is also included within the skill of this area.