Summary of the invention
The applicant is in the process of research Herba Eupatorii Lindleyani pharmacologically active; Find that brown cyanidin treatment hyperlipidaemic conditions is wherein had good result; Especially treat high triglyceride and high serum low-density protein type hyperlipidemia has significant effect. based on this discovery; The applicant is used to prepare the purposes of blood lipid-lowering medicine with brown cyanidin, is applied to triglyceride reducing further, reduces the purposes of serum low-density protein drug.
The medicine of blood fat reducing purposes according to the invention is meant the one type of goods general name that therapeutic effect is arranged with blood fat reducing effect on being of universal significance, and includes but not limited to medicine, health product, nutriment.
The medicine of purposes according to the invention includes but not limited to tablet, injection, injectable powder, capsule, granule.
The medicine of purposes according to the invention; Can be that brown cyanidin and acceptable accessories adopt conventional preparation process to process particular dosage form, can brown cyanidin and excipient substance be processed medicament through the experimental technique of routine to those skilled in the art.Described adjuvant can be a disintegrating agent, includes but not limited to hydroxypropyl starch, hydroxypropyl cellulose, carboxymethyl starch sodium, carboxymethylcellulose calcium, polyvinylpolypyrrolidone etc.; Can be filler, include but not limited to lactose, sucrose, mannitol, microcrystalline Cellulose, dextrin, starch etc.; Can be wetting agent or binding agent, include but not limited to gelling starch, polyvidone, sodium carboxymethyl cellulose etc.; Can be lubricant, include but not limited to magnesium stearate, micropowder silica gel, Macrogol 4000, polyethylene glycol 6000 etc.;
The medicine of purposes according to the invention, formulation method is not restricted, and can be any adoptable preparation process of pharmaceutical field.
The medicine of purposes according to the invention can adopt different medications according to himself characteristic, for example can adopt the method for oral administration, and its preparation formulation can be tablet, capsule, soft capsule, oral liquid, suspension; Also can adopt the parenteral approach, its preparation formulation can be injection solution, suspension for injection etc.
The pharmacological evaluation that the inventor carries out shows that brown cyanidin has the effect of significant blood fat reducing, especially has the effect of extremely significant triglyceride reducing and serum low-density LP.Therefore be applied to treat and/or prevent hyperlipidemia on the clinical drug of purposes according to the invention, especially be applied to treat and/or prevent high triglyceride and serum low-density LP blood fat disease.
The specific embodiment
Following embodiment only is used to provide the concrete preparation way of realizing purposes of the present invention, is not limited to the implementation method of purposes of the present invention.
Among the present invention; The palm fibre cyanidin can adopt following method to extract: after Herba Eupatorii Lindleyani plant drying and crushing; Extract twice through 95% alcohol heating reflux; Each heating two hours extracts gained extractum four times behind the recovery ethanol in ethyl acetate, adopt recrystallization method to obtain brown cyanidin then.
Also can directly buy brown cyanidin chemical compound; Used brown cyanidin is bought to spread out from Shanghai and is won Industrial Co., Ltd. among the following embodiment of the present invention; Through detecting its purity is 98.5%. lindley eupatorium herb general flavone extract; Purchase in Ange Pharmaceutical Co., Ltd, Jiangsu, purity is that 96%. brown cyanidin content are 15%.
Embodiment 1: the preparation of brown cyanidin tablet
Prepare brown cyanidin tablet according to following consumption
Palm fibre cyanidin 5g
Sucrose 100g
Starch 30g
Magnesium stearate 0.5g
Sodium carboxymethyl cellulose 30g
Brown cyanidin mixed forming uniform mixture with sucrose, starch, add an amount of water and powder is granulated.After the drying granule sieved and mix, then tabletting with all the other adjuvants.
Embodiment 2: the particulate preparation of brown cyanidin
Palm fibre cyanidin 5g
Dextrin 25g
Starch 10g
50% ethanol is an amount of
Dextrin, starch are crossed 100 mesh sieves respectively, and with brown cyanidin, dextrin, starch mix homogeneously, ethanol joins mixing in the said mixture, processes granule.
The preparation of embodiment 3 brown cyanidin Emulsions
Palm fibre cyanidin 1g
Soybean oil 20g
Vitamin E 0.8g
Lecithin 2g
Glycerol 2.5g
Water adds to 1000ml
Lecithin, glycerol is scattered in the 800ml water forms water.
Brown cyanidin, vitamin E are joined mix homogeneously formation oil phase in the soybean oil.
Water and oil phase join aqueous phase with oil phase after being preheated to 70 degree respectively, and the even colostrum that gets of high-speed stirred is with the back packing sterilization of the even breast of high pressure homogenization machine.
Embodiment 4 brown cyanidin oral liquids
Palm fibre cyanidin 5g
Mel 30g
Sorbic acid 5g
Fructus Lycii acid sodium 5g
Essence 1ml
Water is an amount of
Each component of above-mentioned amount after the mixing and stirring dissolving, is sealed the bottle oral liquid according to specific standard in water.
Embodiment 5: brown cyanidin injection
Palm fibre cyanidin 3g
Sodium sulfite 20g
Disodium edetate 5g
Water for injection is to 1000ml
Brown cyanidin, sodium sulfite, disodium edetate are joined mix homogeneously in the water for injection respectively, and sterilization back branch is filled to cillin bottle.
Pharmacodynamics test one:
Material and articles for use: brown cyanidin, lindley eupatorium herb general flavone, lovastatin.
Method: the KM mice, male and female half and half, totally 70, random packet is: first group: model control group; Second group: the blank group; The 3rd group: low dosage palm fibre cyanidin group; The 4th group: middle dosage palm fibre cyanidin group; The 5th group: high dose palm fibre cyanidin group; The 6th group: the lovastatin positive controls; The 7th group: the lindley eupatorium herb general flavone positive controls.
Except the blank group, other each treated animals are all with the modeling of hyperlipidemia diet: high fat materials such as 10% cholesterol, 20% Adeps Sus domestica, 2% cholate, 1% propylthiouracil, 10% sucrose are prepared into Emulsion with 15% tween, 5% propylene glycol.The modeling mice is irritated the high lipoprotein emulsion 0.5ml/g of clothes the morning, receives reagent thing 0.2mg/10g afternoon separately.Blank group and model control group all give distilled water contrast, modeling continuously.After the administration 14 days, stop modeling, successive administration is 7 days then, and next day is got blood in drug withdrawal, measures serum triglycerides (TC), serum cholesterol (TG).
Experimental result: the result according to following table 1 can find out that serum TC, TG all raise after the mice modeling, and the modeling success is described.
Lovastatin and lindley eupatorium herb general flavone extract can reduce the TC of hyperlipidemia model animal, but the lindley eupatorium herb general flavone extract does not have effect to reducing TG.
Each administration group of palm fibre cyanidin all demonstrates good effect for reducing blood fat, especially TC is had significant reduction effect, and wherein middle high dose group effect is especially obvious.The while data show, high dose group also produces effect to reducing TG in the brown cyanidin.
Table 1 different pharmaceutical is to the influence of mice serum blood fat
(* p<0.05, expression is compared with the blank group, and model group has on the statistics to be distinguished; Δ p<0.05, Δ Δ p<0.01, Δ Δ Δ p<0.001 is represented respectively to compare with model group, has difference, significantly difference, extremely significantly difference on the statistics)
Pharmacodynamics test two
Laboratory animal: Carnis Coturnicis japonicae, male, body weight 100 ± 10g, raises after being divided into 7 groups at random totally by 70.
Feedstuff: adopted 0.12: 12: 12: 12: 0.004: 76 ratio is mixed cholesterol, Adeps Sus domestica, yolk powder, propylthiouracil, normal feedstuff; Wherein the cholesterol of per unit feedstuff employing is 36g; Evenly be divided into 300 parts, to the amount feeding of every Carnis Coturnicis japonicae according to portion/sky.Method according to test one adopts amount grouping modeling in the following table, and is preceding all around respectively in modeling in the morning, the administration in afternoon; Be the administration in afternoon around the back.
Detect index: the 8th all administrations finish the back and get blood in Carnis Coturnicis japonicae antetheca vein place next day, measure TC, TG, LDL-C (serum low-density LP), HDL-C (serum high-density LP) content in the serum.
Experimental result: can find out that from following data the brown cyanidin of middle high dose all can obviously reduce the content of serum cholesterol, serum triglycerides, serum low-density LP, obviously the content of high density lipoprotein increasing.Under the Isodose, brown cyanidin effect all is superior to the lindley eupatorium herb general flavone extract.
Table 2 different pharmaceutical is to the influence of Carnis Coturnicis japonicae serum albumin
(* p<0.05, expression is compared with blank control group, and model has significant difference; Δ p<0.05, expression is compared with model group, has significant difference)