CN1347874A - Application of small dosage of aminoguanidine in anti-senility and preventing and treating senile diseases - Google Patents
Application of small dosage of aminoguanidine in anti-senility and preventing and treating senile diseases Download PDFInfo
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- CN1347874A CN1347874A CN 01107930 CN01107930A CN1347874A CN 1347874 A CN1347874 A CN 1347874A CN 01107930 CN01107930 CN 01107930 CN 01107930 A CN01107930 A CN 01107930A CN 1347874 A CN1347874 A CN 1347874A
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- aminoguanidine
- senility
- senile
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- glycosylation
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 10
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- 238000006206 glycosylation reaction Methods 0.000 claims abstract description 10
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 claims abstract 2
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 claims abstract 2
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- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000002177 Cataract Diseases 0.000 claims description 4
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims 3
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims 3
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Abstract
The present ivnention relates to the application of small dosage of aminoguanidine and its derivative in antisenility and preventing and treating senile diseases. The dosage is limited to reduce or even eliminate bad sdie effect. The present invention aims at providing one convenient and cheap anti-senility medicine. Aminoguanidine is used to delay senility and prevent and treat senile diseases through two ways: inhibiting glycosylation to block the crosslinking of macromolecule and inhibiting iNOS specifically to protect retina nerve and and brain nerve cell.
Description
But the present invention relates to be applied to anti-ageing in low dose of aminoguanidine and the derivative body thereof and prevent and treat multiple geriatric disease.
Known before more than 100 years aminoguanidine just be used to the treatment of diabetic complication.Because this medicine adopts heavy dose of dispensing when the treatment diabetes, side effects such as feeling sick appears in part patient, headache, its clinical application is restricted at home always.
In recent years, Britain has two patent of invention WO97/23203 and WO97/23204 to register in China, has disclosed this medicine by inhibition inducible nitric oxide synthase (iNOS), and has had treatment diabetes effect.
The present invention relates to aminoguanidine can be used for anti-ageing and control ageing-related multiple geriatric disease by anti-glycosylation and iNOS restraining effect; And the restriction aminoguanidine is in low dose of range of application, and alleviates or eliminate its adverse side effect.
At present, the reliable antiaging agent of effect still belongs to blank, makes multiple and old and feeble closely-related geriatric disease be difficult to be effectively controlled.As atherosclerosis, senile dementia, senile cataract, and eyesight, hearing are degenerated some tumor invasion, senile glaucoma, renal failure, uremia etc. all form, finally make in the body non-glycosylation end product in late period (AGEs) to accumulate relevant with glycosylation.
The purpose of this invention is to provide convenient, the cheap antiaging agent of a kind of medication.
Have now found that, in human and the aging course that Mammals is especially human, constantly be accompanied by protein, nucleic acid in the body, contain macromolecular substance generation glycosylation phenomenon under the condition that does not need enzyme to participate in such as amine lipid.Proteinic amino comprehensively becomes a unsettled Schiff alkali with the carbonyl of reducing sugar, and then the process rearrangement forms the aldehyde amines product, the carbonyl compound (as Fig. 1) of this product process dehydration, rearrangement generation high activity.The free amino group of the same protein of carbonyl compound, nucleic acid, lipid reacts, form AGEs, can be crosslinked between the AGEs by side chain, form the great material of molecular weight, macromolecular substance such as protein can turn to bridge with glycosyl and be linked to be bigger material, cause the infringement of its functional structure.About AGEs and the pathogenetic relation of relative disease are summarized as follows.
(i) Protein Glycosylation Overview makes proteinic elasticity reduction, hardness increase function and structural obstructions.
The collagen protein glycosylation, the conformability that can cause the heart, lung, blood vessel reduces; Take place crosslinkedly between the collagen, cause blood vessel not only to be difficult to diastole but also can not effectively to shrink, and make that matrix increases, basal membrane thickening, cause arteriosclerosis, obturation.
The ophthalmic crystal protein glycosylation causes lenticular opacity, produces cataract.
Low-density lipoprotein (LDL) glycosylation makes scavenger cell Surface L DL acceptor reduce identification and the degraded of LDL, is difficult to be eliminated; AGEs is monocytic chemoattractant, and AGEs under the blood vessel endothelium can the migration under tunica intima of directional induction monocyte, and is fixed in the part, and then promotes monocyte to engulf lipid to develop into foam cell, start atheromatous plaque and form; After the corresponding receptors bind on AGEs and monokaryon-macrophage membrane surface, can stimulate scavenger cell to discharge TNF simultaneously
-α, IL-1, IGF-1, PDGF etc., cause inflammatory reaction, cell growth and the vascular smooth muscle propagation of vessel wall, and the matrix of mediation mesangial cell is synthetic, causing renal failure etc. eventually with renal glomerulus hypertrophy, fibrosis all has substantial connection.In addition, AGEs combines by endotheliocyte with the vascular endothelial cell surface receptor and engulfs, and causes endothelial cell permeability to strengthen, and hyperamization slurry albumen oozes to interior subcutaneous; The also short endothelium synthetic tissue factor of AGEs, thus blood clotting and thrombosis on the arteriosclerosis basis, promoted.
(ii) AGEs can modification of nucleic acids, produces the crosslinked of DNA self and with proteinic crosslinked, can cause transgenation, thereby cause the tumor invasion process that increases with age growth.
(iii) collagen and spandex fiber crosslinked in brain, the muscle tissue causes the degeneration of brain and muscle, makes amnesia, physically-draining, is one of important mechanisms of senile dementia morbidity.
Basically be not expression status under (iv) intravital inducible nitric oxide synthase (iNOS) physiological conditions, when paathogenic factor causes iNOS to express enhancing, the a large amount of nitrogen protoxides of sustainable generation (NO) think that now iNOS expression product NO plays an important role in senile glaucomatous retina neural and axoneuron damage.
The mechanism that aminoguanidine delayed senility, prevented and treated multiple senile disease mainly realizes by two approach:
1. suppress glycosylation (as Fig. 2), block macromolecular crosslinkedly, play delaying senility, preventing and treating atherosclerosis, senile dementia, senile cataract, eyesight, hearing and degenerate renal failure and the morbidity effect that suppresses some tumour.
(1-2) shows the aminoguanidine point of application among Fig. 2, shows that (3-6) mechanism of action of aminoguanidine is similar with the anti-glycosylation medicine PTB effect of having used.
2. suppress iNOS by specificity, play the senile glaucomatous visual deterioration effect of control.
Description of drawings:
Fig. 1 is the Protein Glycosylation Overview process; Fig. 2 is the anti-glycosylation of aminoguanidine, anti-crosslinked action
Claims (3)
1. aminoguanidine or its solvate, hydrate or pharmacologically acceptable salt or its pharmaceutically acceptable derivates that delays senility, prevents and treats multiple and old and feeble relevant geriatric disease.(i) structural formula of aminoguanidine is as follows:
The (ii) following guanidine compound of general formula:
R is pharmaceutically acceptable guanidine derivatives such as amino or methyl, phenyl, alkyl in the formula.
2. according to the described guanidine compound of claim 1, its pharmaceutical dosage is used to prevent and treat atherosclerosis, senile dementia, senile cataract and glomerular sclerosis by anti-glycosylation, prophylaxis of tumours and delaying senility.
3. according to the described guanidine compound of claim 1, its pharmaceutical dosage suppresses iNOS by specificity transcribes, and is used to prevent and treat senile glaucoma, delays eyesight and Aging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01107930 CN1347874A (en) | 2001-03-27 | 2001-03-27 | Application of small dosage of aminoguanidine in anti-senility and preventing and treating senile diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01107930 CN1347874A (en) | 2001-03-27 | 2001-03-27 | Application of small dosage of aminoguanidine in anti-senility and preventing and treating senile diseases |
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| Publication Number | Publication Date |
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| CN1347874A true CN1347874A (en) | 2002-05-08 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 01107930 Pending CN1347874A (en) | 2001-03-27 | 2001-03-27 | Application of small dosage of aminoguanidine in anti-senility and preventing and treating senile diseases |
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| CN (1) | CN1347874A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2409558C2 (en) * | 2009-03-31 | 2011-01-20 | Государственное образовательное учреждение высшего профессионального образования Кабардино-Балкарский государственный университет им. Х.М. Бербекова | Zwitterionic acrylate and methacrylate guanidines |
-
2001
- 2001-03-27 CN CN 01107930 patent/CN1347874A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2409558C2 (en) * | 2009-03-31 | 2011-01-20 | Государственное образовательное учреждение высшего профессионального образования Кабардино-Балкарский государственный университет им. Х.М. Бербекова | Zwitterionic acrylate and methacrylate guanidines |
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