CN105769848A - Application of norathyriol in preparation of medicaments and health-care products for preventing and treating chronic kidney disease - Google Patents
Application of norathyriol in preparation of medicaments and health-care products for preventing and treating chronic kidney disease Download PDFInfo
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- 239000003814 drug Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 208000020832 chronic kidney disease Diseases 0.000 title abstract description 14
- ZHTQCPCDXKMMLU-UHFFFAOYSA-N norathyriol Chemical compound OC1=C(O)C=C2C(=O)C3=C(O)C=C(O)C=C3OC2=C1 ZHTQCPCDXKMMLU-UHFFFAOYSA-N 0.000 title abstract description 14
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 claims description 47
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 claims description 47
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of norathyriol in preparation of medicaments and health-care products for preventing and treating chronic kidney disease and belongs to preparation of ketone compounds as the medicaments. The norathyriol comprises oral medicines, like in the medicaments and the health-care products for preventing and treating chronic kidney disease. Experiments show that the norathyriol fed by intragastric administration has a good preventing and treating effect for mice with hyperuricemia and high glucose-induced kidney injury and uric acid-induced kidney injury and animals with diabetic nephropathy, and can be used for remarkably reducing levels of serum creatinine and urea nitrogen of the animals and remarkably improving kidney functions. Histopathology shows that the norathyriol can be used for significantly improving the changes of glomeruli and kidney tubules caused by hyperuricemia and hyperglycemia. The norathyriol disclosed by the invention has high activity and good development and application prospect.
Description
Technical field
The invention belongs to the preparation method using a kind of ketone compounds as medicine, cause the purposes of the medicine of kidney injury nephropathy particularly to mango aglycone as preparation preventing and treating different pathogeny.
Background technology
Chronic renal disease (chronic kidney disease, CKD) cause of disease is complicated, primary glomerulonephritis, interstitial disease of renal tubule, hypertension, diabetes, gout, hyperuricemia, lupus erythematosus, anaphylactoid purpura, heritability nephropathy etc. all may result in end stagerenaldisease (the end stage of of CKD, CKD
Renal disease, ESRD) the required replacement therapy such as Rend dialysis or renal transplantation, causes the huge economy of patient and stress, and is only capable of the existence of prolongation patient.The sickness rate of American-European countries CKD, between 6～16%, has 23,000,000 Americans to suffer from CKD [Nyman H A.
Renal Dosing in High-Risk Populations. Journal of Infusion Nursing2015,38:210-215].In China, the sickness rate of the big city CKD such as Shanghai, Beijing, Guangzhou is similar to developed country, the highest.Treatment means current for CKD is primarily directed to the treatment of primary disease, and protects the medicine of kidney the deficientest.
Mango aglycone (norathyriol) is a kind of important xanthone compounds, entitled 1,3,6, the 7-Tetrahydroxyxanthones (such as Fig. 1) of chemistry.This compound is widely present in [Sun Wenji in the plants such as Teng Huang section plant Folium Ilicis, Fructus Garciniae oblongifoliae, berry Radix Hyperici Monogyni (Herba Hyperici Monogyni), Moraceae Maclura aurantiaca and Garcinia, rope gold room. the simple and clear handbook of active skull cap components. China Medical Science Press. 1998, the first edition, p414], but content is relatively low.In recent years the multidigit scholar mango aglycone that used chemical synthesis process semi-synthetic and complete synthesis, solve the resource problem [Li Ling of mango aglycone, Song Liudong, Liu Xu, Gao Suo. the full chemical synthesis process of mango aglycone. Chinese invention patent number: ZL 2,010 1 0529474.7].Pharmaceutical research shows that mango aglycone has antioxidation, antitumor, suppression xanthine oxidase and PTP1B activity, improves the multiple pharmacologically actives such as insulin resistant, blood sugar lowering, blood fat reducing, antiinflammatory and Suppress hyperplasia of prostate, but has not yet to see about the report preventing and treating nephropathy.
Summary of the invention
It is an object of the invention to prepare a kind of medicine preventing and treating chronic nephropathy and health product, this medicine and health product with ketone compounds mango aglycone strong for improving renal function pharmacologically active, Renoprotective Effect is obvious.
For realizing object above, approach of the present invention is:
Mango aglycone application in preparation preventing and treating chronic nephropathy medicine and health product.
Described application is: mango aglycone medicinal preparation for oral administration in preparation preventing and treating chronic nephropathy medicine and health product.
Described application is to prepare, with 0.25 ~ 50 mg/kg mango aglycone, the medicinal preparation for oral administration prevented and treated in chronic nephropathy medicine and health product.
Through numerous studies it has been observed that kidney injury animal and diabetic nephropathy animal that uric acid is induced by mango aglycone show preferable preventive and therapeutic effect, gavage gives mango aglycone (0.25
~ 50 mg/kg) can substantially reduce serum creatinine and the urine creatine level of animal, improve renal function.Simultaneously, histopathological study shows, mango aglycone can be obviously improved glomerule and the change of renal tubules caused by metabolic arthritis and height sugar, show the strongest activity, provide the new application of mango aglycone, there is good development prospect, may be used for medicine and the health product of the injury of kidney that the oral preventing and treating many reasons of preparation causes.
Accompanying drawing explanation
Fig. 1 is the chemical structural formula of mango aglycone.
Fig. 2 is Kunming mouse Normal group HE dyeing striograph.
Fig. 3 is Kunming mouse model group HE dyeing striograph.
Fig. 4 is the impact (HE dyeing) on uric acid induction kidney injury of the low dose group 1.0 mg/kg gastric infusion of Kunming mouse mango aglycone.
Fig. 5 is the impact (HE dyeing) on uric acid induction kidney injury of the middle dosage group 2.0 mg/kg gastric infusion of Kunming mouse mango aglycone.
Fig. 6 is the impact (HE dyeing) on uric acid induction kidney injury of the high dose group 4.0 mg/kg gastric infusion of Kunming mouse mango aglycone.
Fig. 7 is the 12.5 of Kunming mouse positive control benzbromarone group
The impact (HE dyeing) on uric acid induction kidney injury of the mg/kg gastric infusion.
Fig. 8 is Kunming mouse blood sugar level Normal group.
Fig. 9 is Kunming mouse blood sugar level sugar nephropathy model group.
Figure 10 is the impact that alloxan sugar nephropathy mouse kidney is damaged by 7.5 mg/kg low dose group mango aglycone gastric infusions.
Figure 11 is the impact that in 15.0 mg/kg, alloxan sugar nephropathy mouse kidney is damaged by dosage group mango aglycone gastric infusion.
Figure 12 is the impact that alloxan sugar nephropathy mouse kidney is damaged by 30.0 mg/kg high dose group mango aglycone gastric infusions.
Figure 13 is the impact that alloxan sugar nephropathy mouse kidney is damaged by positive control drug 250 mg/kg metformin group gastric infusion.
Below in conjunction with detailed description of the invention, the present invention will be further described.Detailed description of the invention includes but is not intended to protection scope of the present invention.
Detailed description of the invention
1. the compounds of this invention impact on the kidney injury that uric acid is induced
60 Kunming mouses are randomly divided into 6 groups, often group 10, respectively dosage group (2.0 mg/kg), mango aglycone high dose group (4.0 in Normal group, model group, mango aglycone low dose group (1.0 mg/kg), mango aglycone
Mg/kg) group and positive control benzbromarone group (12.5 mg/kg).In addition to normal control treated animal, each treated animal equal lumbar injection uric acid 100 mg/kg induces kidney injury, every day 2 times, totally 10 days.Normal group and model group animal gavage give the sodium carboxymethyl cellulose of solvent 0.5% (CMC-Na, each medication group give mango aglycone 1.0,2.0 and 4.0 mg/kg and benzbromarone 12.5 mg/kg respectively, by 20 simultaneously
Ml/kg gastric infusion, every day 1 time, totally 10 days.Pluck eyeball at the end of experiment and take blood, survey serum creatinine and blood urea nitrogen, take right side kidney and do pathological examination.
Result shows, after giving uric acid, Mouse Blood uric acid, creatinine and urea nitrogen levels are significantly raised, statistically significant compared with Normal group.After mango aglycone gastric infusion, blood uric acid, creatinine and urea nitrogen levels the most substantially reduce, and in certain dose dependent (table 1), prompting mango aglycone has the effect improving renal function.
Table 1 mango aglycone is on uric acid inducing mouse renal dysfunction serum creatinine and the impact of blood urea nitrogen
| Group | Dosage (mg/kg) | Uric acid (μm ol/L) | Creatinine (μm ol/L) | Blood urea nitrogen (mmol/L) |
| Normal group | CMC-Na | 115.0 ± 24.8 | 52.1 ± 12.7 | 8.24 ± 2.2 |
| Model group | CMC-Na | 151.2 ± 16.7▲▲ | 74.3 ± 15.9▲▲ | 13.85 ± 2.9▲▲ |
| Mango aglycone | 1.0 | 130.0 ± 18.5* | 63.8 ± 11.4* | 10.37 ± 3.5* |
| 2.0 | 126.9 ± 25.1* | 57.9 ± 10.3** | 9.77 ± 2.8* | |
| 4.0 | 122.8 ± 22.2** | 52.5 ± 10.8** | 9.42 ± 1.8** | |
| Benzbromarone | 12.5 | 132.5 ± 13.4* | 58.4 ± 13.5* | 9.67 ± 2.4* |
x ±s,n = 10. ▲▲ P<0.01,
Compare with Normal group；* P<0.05,** P< 0.01, compare with model control group (t-inspection).
As seen from Figure 3, visible under metabolic arthritis model group animal kidney HE dyeing light microscopic: glomerular sclerosis (1-5%), glomerule atrophy (1-5%), glomerular capillary expansion (1-5%), part renal cells vacuolar degeneration (1-5%).From Fig. 4～7, after mango aglycone medication, mouse kidney pathological change is obviously improved, and part glomerular mesangium thickens, and volume is loose (1-5%), renal tubules no abnormality seen.Benzbromarone treated animal part glomerular mesangium thickens, and volume is loose (5-10%), renal tubules no abnormality seen.Result above prompting mango aglycone significantly improves the kidney injury that metabolic arthritis causes, and has protective effect.
2. the compounds of this invention impact on alloxan inducing mouse sugar nephropathy
Take ICR mice, male, body weight 25 ~ 30
G, fasting 6 hours, freely drink water, in tail vein injecting normal saline or alloxan 60 respectively
Mg/kg, after 72 hours, docking takes blood, uses glucose oxidase method to survey non-fasting glucose, and blood glucose value is more than 11.1
Mmol/L person enters diabetic animal models.According to blood sugar level, animal is divided into Normal group and sugar nephropathy model group, mango aglycone low dose group (7.5
Mg/kg), dosage group (15.0 mg/kg), mango aglycone high dose group (30.0 mg/kg) and positive control drug metformin group (250 in mango aglycone
Mg/kg), give solvent 0.5%CMC-Na and each test medicine, by 20ml/kg gastric infusion, once a day, totally 8 weeks respectively, observe the state of mice every day, weigh weekly Mouse Weight, pluck eyeball during off-test and take blood, 3000
Take serum after r/min is centrifugal, survey blood glucose, serum creatinine and blood urea nitrogen, take kidney, weigh, calculate renal index, take right side kidney and do pathological examination.
Result shows, blood glucose in diabetic mice maintains higher level always, after giving mango aglycone 6 weeks, and 15.0
Mg/kg and 30.0 mg/kg treated animal blood glucose reduce, and compared with diabetic model group, difference is statistically significant.
Diabetic mice after eight weeks serum creatinine and urea nitrogen levels significantly raised, renal hypertrophy, prompting animal diabetic nephropathy occurs.And mango aglycone is administered the serum creatinine and urea nitrogen levels substantially reducing diabetic nephropathy mice eight weeks, renal hypertrophy is also obviously improved, and therefore, prompting chimonin has the effect (table 2,3) improving diabetic nephropathy animal renal function.
The impact of eight weeks fasting glucose non-on alloxan diabetes mice of table 2 mango aglycone gastric infusion
x ±s,n = 10. ▲▲ P<0.01,
Compare with Normal group；* P<0.05,** P< 0.01, compare with model control group (t-inspection).
Continued 2:
Table 3 mango aglycone gastric infusion eight weeks is on alloxan diabetes Mouse Kidney function and the impact of renal index
x ±s,n= 10；▲▲ P<0.01,
Compare with Normal group；* P<0.05,** P< 0.01, compare with model control group (t-inspection).
As seen from Figure 9, diabetic model group animal part renal cortex surface irregularity, visible part glomerule atrophy under kidney HE dyeing light microscopic, part glomerular mesangium thickens, volume is loose (20-30%), part tubular ectasia (1-5%), part renal tubules regeneration (5-10%)；Renal interstitial focal fibrosis, focal lymphocytic infiltration (5-10%), PAS dyeing shows more glomerular mesangial matrixes, and in peony, remaining renal tubules inwall and basement membrane are positive, and PAS strong positive scope is about (10-20%).In Figure 10～13; the pathological change of mango aglycone each dosage group and metformin positive controls kidney substantially alleviates; part glomerular mesangium thickens; volume is loose (10-20%), and renal tubules no abnormality seen is expanded, part renal tubules regeneration (5-10%); renal interstitial has no fibrosis; have no that lymphocytic infiltration, prompting mango aglycone can improve the kidney injury caused by high sugar, have protective effect.
Based on above experiment, the mango aglycone of the present invention application in preparation preventing and treating chronic nephropathy medicine and health product also includes:
Mango aglycone medicinal preparation for oral administration in preparation preventing and treating chronic nephropathy medicine and health product.
With 0.25 ~ 50 mg/kg mango aglycone medicinal preparation for oral administration in preparation preventing and treating chronic nephropathy medicine and health product.
Claims (3)
1. mango aglycone application in preparation preventing and treating chronic nephropathy medicine and health product.
Application the most according to claim 1, is characterized in that: mango aglycone medicinal preparation for oral administration in preparation preventing and treating chronic nephropathy medicine and health product.
Application the most according to claim 1 and 2, is characterized in that: preparing, with 0.25 ~ 50 mg/kg mango aglycone, the medicinal preparation for oral administration prevented and treated in chronic nephropathy medicine and health product.
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Cited By (3)
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| CN107137422A (en) * | 2017-06-08 | 2017-09-08 | 任航 | Application of the plant pectin in treatment gout product |
| CN114732894A (en) * | 2022-04-28 | 2022-07-12 | 南京医科大学第二附属医院 | Application of Perilipin1 in preparation of diabetic nephropathy product |
| CN115068455A (en) * | 2022-07-14 | 2022-09-20 | 中南大学湘雅三医院 | Application of BMS-303141 in preparation of medicine for treating chronic kidney disease |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107137422A (en) * | 2017-06-08 | 2017-09-08 | 任航 | Application of the plant pectin in treatment gout product |
| CN114732894A (en) * | 2022-04-28 | 2022-07-12 | 南京医科大学第二附属医院 | Application of Perilipin1 in preparation of diabetic nephropathy product |
| CN114732894B (en) * | 2022-04-28 | 2023-10-27 | 南京医科大学第二附属医院 | Application of Perilipin1 in preparation of diabetic nephropathy products |
| CN115068455A (en) * | 2022-07-14 | 2022-09-20 | 中南大学湘雅三医院 | Application of BMS-303141 in preparation of medicine for treating chronic kidney disease |
| CN115068455B (en) * | 2022-07-14 | 2023-11-07 | 中南大学湘雅三医院 | Application of BMS-303141 in preparation of medicine for treating chronic kidney disease |
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