CN101007017B - Extract of traditional Chinese medicine having alpha-glucosidase inhibitor activity and its application - Google Patents
Extract of traditional Chinese medicine having alpha-glucosidase inhibitor activity and its application Download PDFInfo
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- CN101007017B CN101007017B CN 200710026300 CN200710026300A CN101007017B CN 101007017 B CN101007017 B CN 101007017B CN 200710026300 CN200710026300 CN 200710026300 CN 200710026300 A CN200710026300 A CN 200710026300A CN 101007017 B CN101007017 B CN 101007017B
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- butyl
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- pyrazine
- deoxynojirimycin
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- 239000000284 extract Substances 0.000 title claims abstract description 52
- 239000003814 drug Substances 0.000 title claims abstract description 25
- 230000000694 effects Effects 0.000 title claims description 17
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 title claims description 16
- 239000003888 alpha glucosidase inhibitor Substances 0.000 title claims description 16
- LXBIFEVIBLOUGU-JGWLITMVSA-N duvoglustat Chemical compound OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-JGWLITMVSA-N 0.000 claims abstract description 60
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims abstract description 33
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims abstract description 33
- LXBIFEVIBLOUGU-UHFFFAOYSA-N Deoxymannojirimycin Natural products OCC1NCC(O)C(O)C1O LXBIFEVIBLOUGU-UHFFFAOYSA-N 0.000 claims abstract description 33
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims abstract description 33
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- 239000000203 mixture Substances 0.000 claims description 21
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 18
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Abstract
The invention discloses anextract of Chinese herbs containing alpha-glycoside enzyme inhibitor, which comprises cytidine, 2-(1',2',3',4'-tetrahydroxylbutyl)-5-(2'',3'',4''-trihydroxybutyl)-pyrazine and 1-deoxynojirimycin. The extract can be obtained from leaves, branches and peels of mulberries. The extract can be used for preparing medicament for treating diabetes.
Description
Technical field
The present invention relates to have the Chinese medicine extract and preparation method thereof and the medical usage of alpha-glucosidase inhibitor activity.
Background technology
Diabetes are a kind of common incretion metabolism diseases that caused by the h and E factor.According to World Health Organization (WHO) (WTO) statistics, present global diabetics surpasses 1.5 hundred million, and the present diabetics of China is about more than 2,000 ten thousand, and expecting 2025 will reach about 4,000 ten thousand.Diabetes and chronic complicating diseases thereof have become after cardiovascular and cerebrovascular vessel and tumor, the third-largest disease of serious threat human health.Treatment of diabetes is mainly set about from insulin secretion accelerating, raising insulin sensitivity, inhibition glycoside hydrolysis enzymatic activity, exciting peroxisome hypertrophy activated receptor g several aspects such as (PPAR-g).Wherein, alpha-glucosidase inhibitor is the novel treatment diabetes medicament of a class that the eighties occurs, its main mechanism is by the α of competitive inhibition small intestinal epimere-glycoside hydrolysis enzymatic activity, reduces and delayed the absorption of carbohydrate, thereby reaches the purpose of blood sugar lowering.The glycoside hydrolase inhibitor medicine of existing clinical practice has acarbose (Acarbose), voglibose (Voglibose), emiglitate (Emiglitate), miglitol (Miglitol) etc.
Chinese patent ZL01113191.8 has introduced " Chinese medicine extract, Preparation Method And The Use with alpha-glucosidase inhibitor activity ", but relating to, this patent from mulberry kwangtung (M.atropurpurea Roxb.), do not extract the preparation Chinese medicine extract, and do not relate in the extract cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-any chemical constituent in 5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine and the 1-deoxynojirimycin.Chinese patent ZL200410018677.4 has introduced " medical composition and its use with alpha-glucoside inhibiting activity ", but relating to, this patent from mulberry kwangtung (M.atropurpurea Roxb.), do not extract the preparation Chinese medicine extract, and do not relate in the extract cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-any chemical constituent in 5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine and the 1-deoxynojirimycin.
Mulberry kwangtung (M.atropurpurea Roxb.) is the Morus plant of extensive distribution of China and area, Guangdong, the extract of its leaf can obviously improve the hyperglycemia symptom of diabetic mice, have good hypoglycemic activity, and be significant dose-effect relationship, and effect is better than the antidiabetic drug glibenclamide, but the unclear [Zou Yuxiao of its active component and mechanism of action, Zheng Xiangming, Liao Sentai etc. the research of Sang Ning tea hypoglycemic activity, Food Science, 2003, (7): 124-127].
Summary of the invention
The object of the present invention is to provide active component of a kind of Chinese medicine extract with alpha-glucosidase inhibitor activity and its production and application.
Chinese medicine extract with alpha-glucosidase inhibitor activity of the present invention, contain cytidine (cytidine), 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-pyrazine [2-(1 ', 2 '; 3 '; 4 '-tetrahydroxybutyl)-5-(2 ", 3 ", 4 " trihydroxybutyl)-pyrazine] and three kinds of compositions of 1-deoxynojirimycin (1-deoxynojirimycin).
Described cytidine (cytidine), 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine [2-(1 '; 2 ', 3 ', 4 '-tetrahydroxybutyl)-5-(2 ", 3 ", 4 " trihydroxybutyl)-pyrazine] and three kinds of compositions of 1-deoxynojirimycin (1-deoxynojirimycin) can be by the arbitrary proportion proportioning.As preferred version, the mass ratio of these three kinds of compositions is followed successively by (1～100): (1～100): (1～100).As preferred plan, the mass ratio of these three kinds of compositions was followed successively by 1: 2: 14.
Described Chinese medicine extract with alpha-glucosidase inhibitor activity can be extracted by leaf, branch and the root bark of Morus plant and obtain preferably extraction acquisition from leaf, branch and the root bark of mulberry kwangtung (Morus atropurpurea Roxb.).
Described Chinese medicine extract with alpha-glucosidase inhibitor activity can be obtained by following method: get dry Guangdong Folium Mori fine powder, water or 10-95% ethanol or methanol eddy or diafiltration are extracted, merge extractive liquid,, be recycled to and do not have the alcohol flavor, add ethanol or methanol and carry out precipitate with ethanol, centrifugal or remove by filter precipitation, supernatant passes through acid-exchange resin, difference water and ammonia eluting, ammonia partial concentration drying must contain the cytidine more than 10%, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 ", 3 ", 4 " and the trihydroxy butyl)-pyrazine; the total alkaloids extract of 1-deoxynojirimycin.
Gained contain cytidine more than 10%, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 " 4 " trihydroxy butyl)-total alkaloids extract of pyrazine and 1-deoxynojirimycin is successively by the HZ-202 strong basic ion exchange resin, HD-2 weak-acid cation-exchange resin, Dowex1 * 2 (OH
-Type) ion exchange resin, SephadexLH-20 column chromatography for separation obtain respectively cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine and pure product of 1-deoxynojirimycin.
Above-mentioned Chinese medicine extract with alpha-glucosidase inhibitor activity can be used for preparing the medicine of treatment and prevent diabetes.The medicine of this treatment and prevent diabetes can be prepared into various dosage forms according to a conventional method, as tablet, pill, capsule, granule or injection or the like.
In order to determine the hypoglycemic effective ingredient or the effective site of Guangdong Folium Mori, we have adopted the targeting under the active guidance to follow the trail of separation method and have studied, and each separated part is carried out active testing.Experimental result shows, isolated cytidine (cytidine), 2-from the Folium Mori of Guangdong (1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " the trihydroxy butyl)-pyrazine [2-(1 ', 2 '; 3 '; 4 '-tetrahydroxybutyl)-5-(2 ", 3 ", 4 " trihydroxybutyl)-pyrazine], 1-deoxynojirimycin (1-deoxynojirimycin) and the effective site that contains these three kinds of compositions all has the active and hypoglycemic effect of strong inhibition alpha-glucosidase.
The present invention proves, cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 " 4 " trihydroxy butyl)-pyrazine, 1-deoxynojirimycin and the effective site that contains above three kinds of compositions has strong inhibition alpha-glucosidase active function; oral separately contain cytidine, 2-(1 '; 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 ", 3 ", 4 " trihydroxy butyl) thereby-effective site of pyrazine and three kinds of compositions of 1-deoxynojirimycin can effectively suppress the active purpose that reaches blood sugar lowering of alpha-glucosidase.
The specific embodiment
The present invention can be elaborated by following examples, but is not limited only to following examples.
The preparation of embodiment one, extract
Dry Guangdong Folium Mori fine powder 500g uses 4L 60% alcohol reflux 2 hours, filters.Filtering residue adds 3L 60% alcohol reflux 2 hours again, filters.Merge extractive liquid, is recycled to no ethanol flavor, adds equal-volume ethanol, the centrifugal precipitation of removing, supernatant passes through 732 (H+ type) strong-acid ion exchange resin, difference water 2L and 0.5N ammonia 4L eluting, ammonia part, concentrate drying get the 2g ninhydrin reaction positive contain cytidine more than 10%, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-total alkaloids extract of pyrazine and 1-deoxynojirimycin.
The preparation of embodiment two, extract
Dry Guangdong Folium Mori fine powder 2000g, extract with 20L 50% ethanol percolation, merge extractive liquid,, be recycled to no ethanol flavor, add equal-volume ethanol, the centrifugal precipitation of removing, supernatant passes through 732 (H+ type) strong-acid ion exchange resin, difference water 3L and 0.5N ammonia 6L eluting, ammonia part, concentrate drying get the 5g ninhydrin reaction positive contain cytidine more than 10%, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-total alkaloids extract of pyrazine and 1-deoxynojirimycin.Total alkaloids extract is successively by the HZ-202 strong basic ion exchange resin, the HD-2 weak-acid cation-exchange resin, Dowex1 * 2 (OH-type) ion exchange resin, Sephadex LH-20 column chromatography for separation obtains cytidine (96% respectively, 32mg), 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 " 4 " trihydroxy butyl)-pyrazine (95%, 57mg) and the 1-deoxynojirimycin (98%, 400mg) pure product.Through respectively with its bibliographical information IR, UV, MS and the NMR data relatively, determined the structural formula of above three chemical compounds.
The structure of embodiment three, chemical compound
(1) structure of cytidine is:
Colourless needle (methanol), C9H13N3O5,1,2,3-indantrione monohydrate shows purple.ESI-MS?m/z：266[M+Na]+，509[2M+Na]+。1H?NMR(400MHz，D2O)δ：7.90(1H，d，J＝7.6Hz，H-6)，6.04(1H，d，J＝7.6Hz，H-5)，5.78(1H，d，J＝3.6Hz，H-1’)，4.23(1H，t，J＝4.8Hz，H-2’)，4.11(1H，t，J＝5.6Hz，H-3’)，4.05(1H，m，H-4’)，3.84(1H，dd，J＝12.8，2.4Hz，H-5a’)，3.72(1H，dd，J＝12.8，4.4Hz，H-5b’)。13C?NMR(100MHz，D2O)δ：162.5(C-4)，153.1(C-2)，143.1(C-6)，95.6(C-5)，90.3(C-1’)，84.1(C-4’)，74.0(C-2’)，69.2(C-3’)，60.6(C-5’)。
(2) 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-structure of 5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine is:
Colourless needle (methanol), C27H32O14,1,2,3-indantrione monohydrate shows purple.ESI-MS?m/z：327[M+Na]+，303[M-H]-。1H?NMR(400MHz，D2O)δ：8.60(1H，s，H-3)，8.42(1H，s，H-6)，5.05(1H，s，H-1’)，3.94(1H，m，H-2”)，3.79-3.73(4H，m)，3.60-3.55(3H，m)]，3.10(1H，br?d，J＝14.4Hz，H-1”)，2.87(1H，m，H-1”)。13C?NMR(100MHz，D2O)δ：154.0(C-2)，153.2(C-5)，144.1(C-6)，142.2(C-3)，74.4(C-3”)，73.4(C-2’)，71.4(C-1’)，71.3(C-2”)，71.1(C-3’)，63.0(C-4’)，62.5(C-4”)，37.5(C-1”)。
(3) structure of 1-deoxynojirimycin is:
Clear crystal (methanol), 196～198 ℃ of mp, C6H13O4N, 1,2,3-indantrione monohydrate shows purple.ESI-MS?m/z：162[M-H]-，186[M+Na]+；1H?NMR(400MHz，D2O)δ：2.35(1H，dd，J＝12.2，10.9Hz，H-1a)，2.44(1H，ddd，J＝9.1，6.2，2.9Hz，H-5)，3.01(1H，dd，J＝12.2，5.1Hz，H-1e)，3.12(1H，t，J＝9.1Hz，H-4)，3.20(1H，t，J＝9.1Hz，H-3)，3.38(1H，ddd，J＝10.9，9.1，5.1Hz，H-2)，3.52(1H，dd，J＝11.7，6.2Hz，H-6a)，3.72(1H，dd，J＝11.7，2.9Hz，H-6b)。13C?NMR(100MHz，D2O)δ：48.6(C-1)，60.4(C-5)，61.3(C-6)，70.8(C-2)，71.4(C-4)，78.3(C-3)。
Embodiment four, animal acute toxicity test
Oral administration
Healthy male mice, body weight 18-22 gram, use respectively cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " the trihydroxy butyl)-pyrazine and 1-deoxynojirimycin and contain the mulberry kwangtung effective site of above composition or compositions (cytidine, 2-(1 ', 2 '; 3 '; 4 '-the tetrahydroxy butyl)-5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine and 1-deoxynojirimycin ratio are 1: 2: 14) be made into aqueous solution and irritate stomach 1.0g/kg, in a continuous week, do not see dead mouse.
Drug administration by injection
Healthy male mice, body weight 18-22 gram, use respectively cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " the trihydroxy butyl)-pyrazine and 1-deoxynojirimycin and contain the mulberry kwangtung effective site of above composition or compositions (cytidine, 2-(1 ', 2 '; 3 '; 4 '-the tetrahydroxy butyl)-5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine and 1-deoxynojirimycin ratio are 1: 2: 14) be made into aqueous solution and carry out lumbar injection, in a continuous week, observe the dead mouse situation.The LD50 value of mulberry kwangtung effective site be 4.82 ± 0.63g/kg, cytidine 5.00g/kg do not see death, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-pyrazine LD50 value is that 3.67 ± 0.51g/kg, 1-deoxynojirimycin LD50 value are 4.97 ± 0.44g/kg.
The activity experiment of embodiment five, inhibition glycosidase
Mulberry kwangtung extract and chemical compound cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-pyrazine; the 1-deoxynojirimycin is respectively with normal saline solution preparation, extracting sample solution 20.0 μ l (the sample final concentration is respectively 0; 0.2; 0.5,2, and 8; 32; 128mg/L) mix, be dissolved in the 0.05M phosphate buffered solution of pH=7.0 with 2.0 μ l glucosidase (0.02U/ μ l), 37 ℃ of incubations 30 minutes, add substrate right-nitrophenol glucoside (2.0mg/ml), test of the variation of the absorbance at λ=400nm place behind the mix homogeneously with the response time.And when enzyme and substrate react under the same conditions when testing inhibiting not by document simultaneously absorbance with the variation in response time.Utilize expert data process software Microcal Origin Professional to handle experimental data, straight slope with the reaction process line is a response speed, this response speed value is made as vertical coordinate, with the inhibitor concentration is the abscissa mapping, available inhibitor is to the IC50 value (even ability drop of half-inhibition concentration---polysaccharide such as the hydrolyzed starch of glucosidase is an original half, needed inhibitor concentration) of glucosidase.Discharging 1.0 μ mol PNP with per minute under this experiment condition is an enzyme activity unit.Acarbose is set blank and negative control group simultaneously as positive controls.The results are shown in Table 1.
Table 1. sample suppresses active experimental result to alpha-glucosidase and maltase
| Sample | The IC50 of alpha-glucosidase | The IC50 of maltase | ? | |
| ?(mg/L)? | (mmol/L) | (mg/L)? | (mmol/L) | ? |
| Acarbose (acarbose) mulberry kwangtung extract (embodiment one) mulberry kwangtung extract (embodiment two) cytidines (cytidine) 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-pyrazine 1-nojirimycin of dechlorination (1-deoxynojirimycin) | 9.2310.310.2?2.45?1.9 40.0 | 0.014--0.010.0070.245 | 11.3 34.1 32.4 6.8 6.23 56.6 | 0.017 - - 0.028 0.023 0.347 |
Embodiment six, to the influence of normal mouse carbohydrate tolerance
(1) experiment material and instrument
Acarbose (Acarbose, glucobay (acarbose)), Bayer A.G; Streptozotocin (streptozotocin, STZ), Sigma company faces with preceding that to be made into concentration with citrate buffer solution be 1% STZ solution; The full vigor type of Luo Kang blood glucose meter, Roche Holding Ag; The mulberry kwangtung extract, self-control.
(2) laboratory animal
The male cleaning level of 7 18-22g in age in week Kunming mouse is available from Guangdong Medical Lab Animal Center (quality certification SCXK (Guangdong) 2003-2002).23 ± 2 ℃ of raising temperatures, lighting hours 12h/d (7:00～19:00 turns on light).
(3) experimental technique
Get 50 male mices, survey fasting glucose, be divided into normal control group, positive drug (glucobay (acarbose) 15.0mgkg-1) matched group at random; Totally 5 groups of mulberry kwangtung extract low dose group (7.5mgkg-1), middle dosage group (15.0mgkg-1) and high dose group (30.0mgkg-1), every group of 10 mices.Administration group its mouse oral gives 0.1ml.10g-1 mulberry kwangtung solution of extract, and matched group waits capacity water.Irritate stomach (ig) starch (10g/kg) 0.5ml behind the 10min, respectively at surveying blood glucose to 0.5h, 1h, 2h behind the starch.The results are shown in Table 2.
(4) experimental result
Table 2 mulberry kwangtung extract is to the influence of normal mouse carbohydrate tolerance
| Group | Dosage (mgkg-1) | Fasting glucose (mmolL-1) | 0.5h blood glucose (mmolL-1) | 1h blood glucose (mmolL-1) | 2h blood glucose (mmolL-1) |
| Matched group glucobay (acarbose) mulberry kwangtung extract (embodiment two) mulberry kwangtung extract (embodiment two) mulberry kwangtung extract (embodiment two) | 15.07.5 15.030.0 | 3.06±0.123.13±0.063.50±0.21?3.24±0.133.09±0.53 | 15.03±2.314.0±0.51 ** 11.0±1.36 *?8.05±1.47 *?5.1±1.82 ** | 16.31±3.125.32±0.78 **?12.56±2.10 *?9.12±1.42 *?6.01±0.98 * | 6.21±0.213.6±0.45 **?5.34±0.37 *5.28±0.56 *?4.68±0.39 * |
*P＜0.05,
*P＜0.01vs matched group
By table 2 as seen, normal mouse significantly raises to 0.5h, 1h blood glucose behind the starch, and 2h bleeding from anus glycosyl originally returns to fasting blood sugar.The mulberry kwangtung extract can significantly reduce mice to 0.5h, 1h blood glucose value behind the starch, and high dose can also significantly reduce 2h blood glucose.
Embodiment seven, to the influence of streptozotocin model mice fasting glucose
(1) experiment material and instrument
Acarbose (Acarbose, glucobay (acarbose)), Bayer A.G; Streptozotocin (streptozotocin, STZ), Sigma company faces with preceding that to be made into concentration with citrate buffer solution be 1% STZ solution; The full vigor type of Luo Kang blood glucose meter, Roche Holding Ag; The mulberry kwangtung extract, self-control.
(2) laboratory animal
The male cleaning level of 7 18-22g in age in week Kunming mouse is available from Guangdong Medical Lab Animal Center (quality certification SCXK (Guangdong) 2003-2002).23 ± 2 ℃ of raising temperatures, lighting hours 12h/d (7:00～19:00 turns on light).
(3) experimental technique
Get 60 male mices, except that 10 as the normal control group, the equal lumbar injection 100mg/kg of all the other mices streptozotocin solution, afterbody is got blood and is surveyed blood glucose value behind the 72h, select 50 of the mices of blood glucose＞11mmo/L, be divided into 5 groups at random, that is: diabetic model group (DM); Mulberry kwangtung extract low dose group (7.5mgkg-1), middle dosage group (15.0mgkg-1) and high dose group (30.0mgkg-1).Irritate stomach every day 1 time, successive administration 30d, every 10d weigh 1 time, adjust dosage according to body weight; Respectively at the 10th, 20, behind the 30d last ig 2h (fasting 12h), mouse tail is got blood and is surveyed blood glucose value.Normal control group and model control group are irritated stomach and are given the equivalent normal saline.The results are shown in Table 3.
(4) experimental result
Table 3 mulberry kwangtung extract is to the influence of streptozotocin model mice fasting glucose
| Group | Dosage (mgkg-1) | Fasting glucose (mmolL-1) | 10d blood glucose (mmolL-1) | 20d blood glucose (mmolL-1) | 30d blood glucose (mmolL-1) |
| Normal control group model group glucobay (acarbose) mulberry kwangtung extract (embodiment two) | 15.07.515.030.0? | 3.06±0.1217.23±3.24 ** 16.13±2.06 **?16.50±1.31 **?16.06±2.43 ** 15.99±2.83 ** | 3.43±0.3119.3±2.62 ** 13.07±1.53 **△△14.24±1.96 **△△13.24±1.37 **△△12.24±2.69 **△△ | ?3.81±0.12?21.03±4.18 ** 11.32±2.78 **△△?13.36±2.18 **△△?12.34±1.56 **△△?10.51±2.18 **△△ | ?3.31±0.11?22.15±3.42 ** 9.62±1.54 **△△?11.37±1.36 **△△?10.67±0.90 **△△?9.46±2.45 **△△ |
*P＜0.01vs normal control group; △ △ P＜0.01vs model group
As can be seen from Table 3, the model group mice is compared with the normal control group, and blood sugar level obviously raises, and illustrates to use streptozotocin to cause the success of diabetic mice model.Compare with model control group, the basic, normal, high dosage group of mulberry kwangtung extract obviously reduces at 10d blood glucose, and 20d, 30d blood glucose decrease than 10d, has significant difference (P＜0.01) with model group.Above experimental result shows, takes the mulberry kwangtung extract fasting blood glucose level tool of streptozotocin diabetic mice is improved significantly.
With obtain in the foregoing description containing cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine and 1-deoxynojirimycin above three kinds of compositions, total contents are 10-90%; mix by recipe quantity with adjuvant from the effective site that Mulberry extracts; granulation, can be made into dosage forms such as tablet, capsule, be used for the treatment of diabetes as alpha-glucosidase inhibitor.
From above result of study, can draw the present invention and have following advantage:
The present invention from the plant resources of China's abundant, find to contain cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " the trihydroxy butyl)-the above three kinds of one-tenth of pyrazine, 1-DNJ be grouped into, total content is the new resources of mulberry kwangtung active component in pharmacy of 10-90%.
Among the present invention contain cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-the active component definite ingredients of 5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine, three kinds of compositions of 1-DNJ; toxicity is little, and pharmacological action is strong, has good prospect in medicine.
3. the raw material of substance mulberry kwangtung resource among the present invention is extensive, inexpensive, and preparation technology is simple.
Among the present invention contain cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 " 4 " trihydroxy butyl)-the above three kinds of one-tenth of pyrazine, 1-DNJ be grouped into, total content is that the active component of 10-90% can with pharmaceutically acceptable excipients, adopt the conventional method of this area to be prepared into various formulations, such as tablet, pill, capsule, granule, injection etc. Dosage be 10-500mg/ people/time, every day 1-3 time.
Claims (6)
1. Chinese medicine extract with alpha-glucosidase inhibitor activity is characterized in that: this extract is to be extracted by the leaf of Morus plant mulberry kwangtung, branch and root bark to obtain; Described extract contain cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 ", 3 ", 4 " trihydroxy butyl)-pyrazine and three kinds of compositions of 1-deoxynojirimycin.
2. the Chinese medicine extract with alpha-glucosidase inhibitor activity according to claim 1, it is characterized in that: described cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-mass ratio of pyrazine and three kinds of compositions of 1-deoxynojirimycin is 1～100: 1～100: 1～100.
3. the Chinese medicine extract with alpha-glucosidase inhibitor activity according to claim 2, it is characterized in that: described cytidine, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-mass ratio of pyrazine and three kinds of compositions of 1-deoxynojirimycin is 1: 2: 14.
4. the Chinese medicine extract with alpha-glucosidase inhibitor activity according to claim 1, it is characterized in that obtaining: get dry Guangdong Folium Mori fine powder by following method, water or 10-95% ethanol or methanol eddy or diafiltration are extracted, merge extractive liquid,, be recycled to and do not have the alcohol flavor, add ethanol or methanol and carry out precipitate with ethanol, centrifugal or remove by filter precipitation, supernatant is by acid-exchange resin, respectively water and ammonia eluting, ammonia partial concentration drying must contain the cytidine more than 10%, 2-(1 ', 2 ', 3 ', 4 '-the tetrahydroxy butyl)-5-(2 "; 3 ", 4 " and the trihydroxy butyl)-total alkaloids extract of pyrazine and 1-deoxynojirimycin.
5. as each described Chinese medicine extract application in the medicine of preparation treatment and prevent diabetes in the claim 1 to 4 with alpha-glucosidase inhibitor activity.
6. application according to claim 5 is characterized in that: the medicine of described treatment and prevent diabetes is prepared into tablet, pill, capsule, granule or injection according to a conventional method.
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| CN101129476B (en) * | 2006-08-21 | 2013-07-24 | 中国医学科学院药物研究所 | Application of mulberry twigs alkaloid valid target in preparing antidiabetics medicament |
| CN102018766B (en) | 2009-09-16 | 2013-03-06 | 博仲盛景医药技术（北京）有限公司 | Plant extractive, extraction method and application thereof as well as composite comprising same |
| TWI484970B (en) * | 2010-09-16 | 2015-05-21 | Botan Century Beijing Co Ltd | A plant extract, compositions containing same, a method of extraction and uses thereof |
| CN102190615B (en) * | 2011-04-08 | 2012-12-19 | 长沙华诚生物科技有限公司 | Method for extracting and separating 1-deoxynojirimycin from mulberry leaves |
| CN102204985A (en) * | 2011-06-10 | 2011-10-05 | 广东省农业科学院蚕业与农产品加工研究所 | Compound lychee seed hpyerglycemic particles and preparation method thereof |
| JP5876856B2 (en) * | 2013-08-02 | 2016-03-02 | 中国医学科学院薬物研究所 | Use of an effective fraction of alkaloids derived from mulberry branches to prepare hypoglycemic agents |
| JP2016011305A (en) * | 2015-09-24 | 2016-01-21 | 中国医学科学院薬物研究所 | Use of effective fraction of alkaloid originating from mulberry branch for preparing hypoglycemic medicine |
| CN107536871A (en) * | 2017-09-13 | 2018-01-05 | 中国科学院动物研究所 | A kind of preparation method for Traditional Chinese medicine for decreasing blood sugar extract |
| CN114010683A (en) * | 2021-12-17 | 2022-02-08 | 北京五和博澳药业股份有限公司 | Application of mulberry extract in preparation of medicine for treating pancreas-related diseases |
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| CN1559539A (en) * | 2004-02-23 | 2005-01-05 | 南开大学 | Medicinal mixture possessing alpha glycocidase inhibiting activity and its use |
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