CN1650870A - Berberine compound sugar reducing medicine - Google Patents
Berberine compound sugar reducing medicine Download PDFInfo
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- CN1650870A CN1650870A CN 200410093947 CN200410093947A CN1650870A CN 1650870 A CN1650870 A CN 1650870A CN 200410093947 CN200410093947 CN 200410093947 CN 200410093947 A CN200410093947 A CN 200410093947A CN 1650870 A CN1650870 A CN 1650870A
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- Prior art keywords
- berberine
- sugar reducing
- compound sugar
- reducing medicine
- berberine compound
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- 229940093265 berberine Drugs 0.000 title claims abstract description 58
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 239000003814 drug Substances 0.000 title claims abstract description 37
- -1 Berberine compound Chemical class 0.000 title claims description 29
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229940100389 Sulfonylurea Drugs 0.000 claims abstract description 10
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims description 17
- 229920002472 Starch Polymers 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 239000008107 starch Substances 0.000 claims description 14
- 235000019698 starch Nutrition 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 12
- 239000008187 granular material Substances 0.000 claims description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 239000002002 slurry Substances 0.000 claims description 8
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
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- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
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- 238000013270 controlled release Methods 0.000 claims description 2
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 claims description 2
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- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
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- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 2
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- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 claims description 2
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- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 12
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- VKJGBAJNNALVAV-UHFFFAOYSA-M Berberine chloride (TN) Chemical compound [Cl-].C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 VKJGBAJNNALVAV-UHFFFAOYSA-M 0.000 description 8
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A hypoglycemic compound berberine for decreasing blood sugar, blood fat and blood viscosity and lowering blood pressure is prepared from the sulfonylurea kind of medicine and berberine.
Description
Technical field
The present invention relates to a kind of medicine, particularly relate to a kind of berberine compound sugar reducing medicine for the treatment of diabetes.
Background technology
Along with the raising of people's living standard, the sickness rate of global diabetes is ascendant trend year by year, and only China just has 6,000 ten thousand diabeticss at present, thereby diabetes have become the third-largest disease that threatens human health after malignant tumor, cardiovascular disease.Diabetes are a kind of common endocrine disturbance's complex disease, and the diabetics great majority are with the complication of hyperlipidemia, hypertension, high blood viscosity (three-hypers disease).According to domestic and international associated mechanisms investigation, diabetics has 20-39% with hypertension, and 14-52% is with coronary heart disease, and the overweight people accounts for 80% in the diabetics, and the general blood fat height of overweight people, blood viscosity is also high.The reason of diabetes death has more than 70% for due to the complication, and a diabetics generally suffers from two or more complication.Modern medicine study proves, treats diabetes merely and wants to obtain desired result and be difficult to reach, and need treat complication in principle in the treatment diabetes and just can reach better curative effect.The sulfonylurea medicine is the common antidiabetic drug of a line that uses clinically at present, the blood sugar lowering mechanism of this class antidiabetic drug is the beta cell that directly acts on islets of langerhans rapidly, reach the purpose of blood sugar lowering to stimulate beta cell to discharge insulin, but can produce bigger side effect during big this class medicine of the long-term taking dose of patient.It is that China doctor finds in practice that berberine (berberine) can be treated diabetes, and multidigit doctor clinical practice proof berberine truly have blood sugar reducing function, but onset is slow, generally need more than two weeks, and dosage is slightly larger, is generally 0.4g * 3/d or higher.Think that through pharmacology and clinical practice research the blood sugar lowering mechanism of berberine is directly not stimulate beta cell, but increase the sensitivity of beta cell, belong to the sensitizer category of islets of langerhans, and have the effect that promotes pancreatic cell regeneration and recover islet function.In order when reaching the identical treatment effect, to reduce the dosage of sulfonylurea hypoglycemic agent, take the side effect that produces behind this medicine to reduce the patient, and overcome the slow shortcoming of berberine onset, at present clinically methods that adopt above-mentioned two kinds of medicines to share improve the blood sugar lowering curative effect more, have listed independent use berberine or sulfonylurea medicine and both contrast therapy data when share in the following table:
Treatment disease case load uses medicine total effective rate research conclusion
Type ii diabetes 20 routine diamicron 70%
18 routine berberines 72.3%
40 routine diamicron+berberines 95% have share synergism P＜0.05
Type ii diabetes 45 routine glipizides 71.1%
50 routine glipizide+berberines 98% have share synergism P＜0.01
Type ii diabetes 10 routine glyburide 70%
12 routine berberines 75%
18 routine glyburide+berberines 94.4% have share synergism P＜0.05
Give an example as can be seen from above-mentioned, when taking sulfonylurea medicine (diamicron, glipizide, glyburide etc.) or berberine merely and both curative effect difference highly significants when share, the also hypoglycemic activity of berberine and not second to the sulfonylurea medicine as can be seen simultaneously, and berberine treatment type ii diabetes specificity is strong, and it does not have hypoglycemic activity to type i diabetes and the normal person of blood glucose.Because the patient takes cumbersomely when share the folk prescription medicine, and dosage form is also undesirable.But do not see the compound preparation of these two kinds of medicines in the market as yet.
Summary of the invention
In order to address the above problem, to the object of the present invention is to provide and a kind ofly can treat hyperglycemia and diabetic syndrome, the tangible berberine compound sugar reducing medicine of taking convenience and synergism.
In order to achieve the above object, berberine compound sugar reducing medicine provided by the invention mainly by fineness be the sulfonylurea medicine of 0.1-350 μ m and berberine that fineness is 1-350 μ m with 1: the weight ratio of 3-250 combines.
Described berberine compound sugar reducing medicine also comprises diluent, binding agent, disintegrating agent, lubricant, fluidizer, antitack agent and slow releasing agent, and can make general dose, various oral tablet, capsule, granule and the powder of slow release, controlled release through suitable technology.
Described diluent is any in starch, dextrin, kaolin, sorbitol, mannitol, the cellulose; Binding agent is any in ethanol, water, starch slurry, dextrin slurry, gelatine size, Macrogol 2000, Macrogol 4000, polyethylene glycol 6000, sodium carboxymethylcellulose pyce, sodium alginate, zein, polyvinyl alcohol, the polyvinylpyrrolidone; Disintegrating agent is any in alginic acid, hydroxymethyl starch, modified starch, microcrystalline Cellulose, crosslinked Carboxymethyl cellulose sodium, hydroxypropyl cellulose, methylcellulose, xylitol, citric acid, tartaric acid, carbamide, lecithin, silica sol, Tween 80, the pregelatinized Starch; Lubricant is any in magnesium stearate, dimethicone, hexadecanol, the Stepanol MG; Fluidizer is micropowder silica gel; Antitack agent is any in Pulvis Talci, the magnesium trisilicate; Slow releasing agent is any in ethyl cellulose, wax fat, cellulose acetate, the polyacrylic resin.
Described berberine can be a free alkali, can also be its salt, and it can extract from natural Rhizoma Coptidis, and also available chemical method is synthetic.
Described berberine compound sugar reducing medicine also can add edible essence and correctives.
Berberine compound sugar reducing medicine provided by the invention mainly is to utilize the synergism between berberine and two kinds of principal agents of sulfonylurea to improve the blood sugar lowering curative effect, but also can blood fat reducing, fall that blood is sticking, blood pressure lowering.In addition, two kinds of principal agents among the present invention all pass through micronization processes, and its dissolution and human bioavailability are obviously improved, thereby the patient just can take less dosage, take the side effect that produces behind the sulfonylurea medicine thereby can reduce.In addition, the patient is each only need to take the effect that a kind of medicine just can reach blood sugar lowering and treat the syndrome that causes thus, thereby very convenient.
The specific embodiment
Below in conjunction with specific embodiment berberine compound sugar reducing medicine of the present invention is elaborated.
Embodiment 1: the berberine compound Jiangtang capsule
Per 1000 berberine compound Jiangtang capsules contain following material:
Gliclazide 20g
Berberine hydrochloride 200g
Soluble starch 70g
Polyvinylpyrrolidone 4g
Take by weighing each raw material respectively by above-mentioned prescription, then gliclazide and berberine hydrochloride are passed through micronization processes respectively, its fineness is reached≤40 μ m.Soluble starch and gliclazide are diluted with the equivalent incremental method, and mix homogeneously, and then with the berberine hydrochloride mixing, add polyvinylpyrrolidone at last and pack into No. 0 or No. 1 capsule, loam cake, polishing, packing can make 1000 berberine compound Jiangtang capsules provided by the invention.
Embodiment 2: the berberine compound metformin
Per 1000 berberine compound metformins contain following material:
Glibenclamide 1.25g
Berberine hydrochloride 200g
Modified starch 40g
Microcrystalline Cellulose 20g
10% polyvinylpyrrolidonesolution solution 12g
20% starch slurry 10g
Magnesium stearate 3g
Take by weighing each raw material respectively by above-mentioned prescription, with glibenclamide and berberine hydrochloride process micronization processes, so that glibenclamide fineness≤25 μ m, berberine hydrochloride fineness≤40 μ m.Each adjuvant is crossed 100 mesh sieves, then with glibenclamide and microcrystalline Cellulose and modified starch with the abundant mix homogeneously of equivalent incremental method, again with berberine hydrochloride with the abundant mix homogeneously of equivalent incremental method, add 10% polyvinylpyrrolidonesolution solution subsequently, add the continuation of 20% starch slurry again and stir and make soft material and cross the granulation of 16 mesh sieves.Wet granular is carried out drying under 50～60 ℃, make dried granule and magnesium stearate mix homogeneously, and then, measure that to calculate slice behind the content heavy, and select suitable punch die to carry out tabletting can to make 1000 berberine compound metformins provided by the invention through 16 mesh sieve granulate.
Embodiment 3: the berberine compound hypoglycemic granule
Per 1000 bags of berberine compound hypoglycemic granules contain following material:
Glipizide 2.5g
Berberine tannate 200g
Xylitol 50g
Soluble starch 30g
Hydroxypropyl cellulose 15g
10% starch slurry 20g
Edible essence 0.5g
Take by weighing each raw material respectively by above-mentioned prescription, glipizide and berberine tannate through micronization processes, are made glipizide fineness≤30 μ m, berberine tannate fineness≤40 μ m.With glipizide and xylitol, soluble starch, hyprolose with equivalent incremental method mix homogeneously gradually, again with the abundant mix homogeneously of berberine tannate.Add 10% starch slurry then and make soft material and mistake 14 mesh sieves, wet granular is carried out drying under 50～60 ℃, dried granule is crossed 14 mesh sieve granulate, and slowly spraying into edible essence under the stirring condition, seal and measure content after 30 minutes and calculate every bag charge weight, last packing, sealing, packing can make 1000 bags of berberine compound hypoglycemic granules provided by the invention.
Embodiment 4: the berberine compound blood-sugar reducing powder
Per 1000 bags of berberine compound blood sugar lowering powders contain following material:
Gliquidone 12.5g
Berberine tannate 250g
Xylitol 50g
Edible essence 0.5g
Take by weighing each raw material respectively by above-mentioned prescription,, make its fineness≤30 μ m and≤40 μ m respectively gliquidone and berberine tannate elder generation process micronization processes.Gliquidone and xylitol are diluted and mix homogeneously with the equivalent incremental method, and then with the berberine tannate mixing.Be distributed into 1000 bags of compound antihypelipidemic powders after sneaking into edible essence.
In order to verify the curative effect of berberine compound sugar reducing medicine treatment diabetes and complication thereof, now the capsule that is listed as neat special one-tenth with the berberine dative is that example is taken test to the patient, simultaneously to taking the folk prescription berberine and folk prescription gliclazide therapeutic effect compares test.Taking hypoglycemic compound capsule 21 people is the moderate II type diabetes patient, hypertension 4 people wherein, high 8 people of blood fat, high 6 people of blood viscosity.Single clothes gliclazide 7 people are the moderate II type diabetes patient, hypertension 1 people wherein, high 4 people of blood fat.Single clothes berberine 8 people are the moderate II type diabetes patient, hypertension 3 people wherein, high 4 people of blood fat.Above patient age is all at 40～65 years old.
Therapeutic Method: treat a course of treatment (one month), withdraw other medicines before the treatment course of treatment of maintenance dose, two week and the moderate exercises of all keeping on a diet.
Test item: fasting glucose, use the glucose enzyme process; Blood fat (checking triglyceride and T-CHOL), blood pressure, hepatic and renal function.
Detection mode: the index of identical items is respectively checked in the front and back of three groups of first courses of treatment of patient, detects above every index again after keeping the course of treatment.
Diabetes deliberated index: produce effects: fasting glucose descends＞50%, and effectively: fasting glucose decline 30-49%, invalid: fasting glucose descends＜30%.
Medication dose and method: every hypoglycemic compound capsule contains gliclazide 20mg, berberine hydrochloride 200mg: 2 * 3/d of therapeutic dose, 1 * 3/d of maintenance dose.
Gliclazide: therapeutic dose 80mg * 2/d, maintenance dose 80mg/d;
Berberine: therapeutic dose 0.4g * 3/d, maintenance dose 0.2 * 3/d.
Therapeutic outcome: clothes gliclazide 7 philtrum fasting glucose descend 3 routine produce effects (42.8%) are arranged, and 2 examples are (28.57%) effectively, total effective rate 71.43%.Hypertension and blood fat do not have significant change.
Clothes Berberine Tablet 8 people, wherein fasting glucose descends 4 routine produce effects (50%), and 2 examples are (25%) effectively, total effective rate 75%.Hypertension 3 people have 2 examples to recover normal, and 1 routine blood pressure is near normally higher slightly.4 people that blood fat is high have 3 people to recover normally, and 1 people's blood fat descends obviously, continue to take medicine to be expected to recover normal.
Clothes hypoglycemic compound capsule 21 philtrum blood glucose remarkable 13 examples (61.9%) that descend, effective 7 examples (35%), total effective rate 96.9%.Hypertension 4 people have 3 people to recover normally, and 1 people's blood pressure drops is also obvious, and the conscious dizziness of patient, feeling of fullness in the head symptom turn for the better by and large.High 4 people of blood fat have 3 people to recover normally, and 1 people is also near normal, and hepatic and renal function is treated the front and back no significant difference.Illustrate that from above-mentioned examination clothes situation the curative effect of hypoglycemic compound capsule is apparently higher than folk prescription.In addition, the gliclazide dosage in the berberine compound Jiangtang capsule reduces than folk prescription dosage, and it is normal to treat and keep the viewing duration hepatic and renal function.The untoward reaction of also not having other takes place.Therefore, we can say that this compound hypoglycemic agent is safe, and be well suited for the complication patient of diabetes with hypertension and hyperlipidemia.
Claims (5)
1, a kind of berberine compound sugar reducing medicine is characterized in that: described berberine compound sugar reducing medicine mainly by fineness be the sulfonylurea medicine of 0.1-350 μ m and berberine that fineness is 1-350 μ m with 1: the weight ratio of 3-250 combines.
2, berberine compound sugar reducing medicine according to claim 1, it is characterized in that: described berberine compound sugar reducing medicine also comprises diluent, binding agent, disintegrating agent, lubricant, fluidizer, antitack agent and slow releasing agent, and can make general dose, various oral tablet, capsule, granule and the powder of slow release, controlled release through suitable technology.
3, berberine compound sugar reducing medicine according to claim 1 is characterized in that: described diluent is any in starch, dextrin, kaolin, sorbitol, mannitol, the cellulose; Binding agent is any in ethanol, water, starch slurry, dextrin slurry, gelatine size, Macrogol 2000, Macrogol 4000, polyethylene glycol 6000, sodium carboxymethylcellulose pyce, sodium alginate, zein, polyvinyl alcohol, the polyvinylpyrrolidone; Disintegrating agent is any in alginic acid, hydroxymethyl starch, modified starch, microcrystalline Cellulose, crosslinked Carboxymethyl cellulose sodium, hydroxypropyl cellulose, methylcellulose, xylitol, citric acid, tartaric acid, carbamide, lecithin, silica sol, Tween 80, the pregelatinized Starch; Lubricant is any in magnesium stearate, dimethicone, hexadecanol, the Stepanol MG; Fluidizer is micropowder silica gel; Antitack agent is any in Pulvis Talci, the magnesium trisilicate; Slow releasing agent is any in ethyl cellulose, wax fat, cellulose acetate, the polyacrylic resin.
4, berberine compound sugar reducing medicine according to claim 1 is characterized in that: described berberine can be a free alkali, can also be its salt, and it can extract from natural Rhizoma Coptidis, and also available chemical method is synthetic.
5, berberine compound sugar reducing medicine according to claim 1 is characterized in that: described berberine compound sugar reducing medicine also can add edible essence and correctives.
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| CN 200410093947 CN1650870A (en) | 2004-12-16 | 2004-12-16 | Berberine compound sugar reducing medicine |
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| CN 200410093947 CN1650870A (en) | 2004-12-16 | 2004-12-16 | Berberine compound sugar reducing medicine |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101874833A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | The New Application of the Processed Products of Coptidis Coptidis Rooted in Wine |
| CN104398513A (en) * | 2014-09-12 | 2015-03-11 | 河南普瑞制药有限公司 | Medicinal composition for increasing dissolution rate of racanisodamine and preparation method thereof |
| WO2015097642A1 (en) * | 2013-12-26 | 2015-07-02 | Rao Raavi Chandra Sekhar | Composition for treating cancer and method of synthesizing the same |
| CN111643466A (en) * | 2020-07-27 | 2020-09-11 | 江苏长江药业有限公司 | Preparation method of berberine hydrochloride tablets |
| CN114642721A (en) * | 2022-04-24 | 2022-06-21 | 华裕(无锡)制药有限公司 | Glipizide tablet preparation for treating diabetes and preparation method thereof |
-
2004
- 2004-12-16 CN CN 200410093947 patent/CN1650870A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101874833A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | The New Application of the Processed Products of Coptidis Coptidis Rooted in Wine |
| WO2015097642A1 (en) * | 2013-12-26 | 2015-07-02 | Rao Raavi Chandra Sekhar | Composition for treating cancer and method of synthesizing the same |
| CN104398513A (en) * | 2014-09-12 | 2015-03-11 | 河南普瑞制药有限公司 | Medicinal composition for increasing dissolution rate of racanisodamine and preparation method thereof |
| CN111643466A (en) * | 2020-07-27 | 2020-09-11 | 江苏长江药业有限公司 | Preparation method of berberine hydrochloride tablets |
| CN114642721A (en) * | 2022-04-24 | 2022-06-21 | 华裕(无锡)制药有限公司 | Glipizide tablet preparation for treating diabetes and preparation method thereof |
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