CN103349671A - Resveratrol and spirulina composition and preparations and preparation method thereof - Google Patents
Resveratrol and spirulina composition and preparations and preparation method thereof Download PDFInfo
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- CN103349671A CN103349671A CN2013103360324A CN201310336032A CN103349671A CN 103349671 A CN103349671 A CN 103349671A CN 2013103360324 A CN2013103360324 A CN 2013103360324A CN 201310336032 A CN201310336032 A CN 201310336032A CN 103349671 A CN103349671 A CN 103349671A
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- resveratrol
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- ethanol
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Abstract
The invention relates to a resveratrol and spirulina composition and preparations and a preparation method thereof. The composition comprises spirulina and high-purity resveratrol with the purity higher than 80%; the composition further comprises an astragalus root extract, a tartary buckwheat extract and vitamin C; and a solid preparation is prepared from the composition and adjuvants, wherein the adjuvants comprise hydroxymethyl cellulose, microcrystalline cellulose and beta-cyclodextrin, and the beta-cyclodextrin can be used for improving the solubility and stability of the composition and improving the bioavailability of the solid preparation. The solid preparation disclosed by the invention can be used for promoting the recovery of islet cells, improving glucose tolerance, lowering blood viscosity and the brittleness of capillaries, promoting blood circulation, lowering blood sugar and blood fat and protecting the liver, and has a very good treatment effect on the prevention or treatment of diabetes, complications of diabetes and cardio-cerebral vascular diseases.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, particularly a kind of resveratrol Spirulin composition and preparation and method for making.
Background technology
Diabetes are a kind of commonly encountered diseases, and about 50% diabetes patient is associated with the multiple infirmitiess of age such as hyperlipidemia according to statistics, and diabetes and relevant complication thereof have become quite great public health problem.
Resveratrol is called again resvertrol, chemistry (E)-3 by name, 4 ', 5-trihydroxy stilbene is a kind of biological very strong natural polyphenol class material, be mainly derived from the plants such as Semen Vitis viniferae skin slag, Rhizoma Polygoni Cuspidati, Semen arachidis hypogaeae, it is white needle-like crystals, is soluble in ethanol, acetone and other organic solvent; Resveratrol or a kind of natural antioxidant can blood viscosity lowering, and anti-platelet clotting and vasodilation keep unblocked blood flowing, have slow down aging, regulate blood fat, the functions such as protection cardiovascular and cerebrovascular vessel, anti-hepatitis; But because the resveratrol unstable chemcial property, and poorly water-soluble, therefore there are the shortcomings such as oral absorptivity is poor, bioavailability is low, cause its application to be subjected to a certain extent restriction.
Spirulina is by filamentous unicellular or that many cells form, also be that a kind of photosynthetic autotrophs are biological, contain photosynthetic synusia, vitamin, protein, unsaturated fatty acid, trace element, carbohydrate, carotene etc. in its frustule, it has multiple biological activity, effects such as nourishing, benefiting QI and nourishing blood has widely purposes at medical health field.
Disclose resveratrol and spirulina are mixed for treating respectively diabetes with other materials report in the prior art, disclose a kind of Chinese medicine that is formed by the Radix Astragali, spirulina, Fructus Schisandrae Chinensis etc. such as CN102920907 and be used for the treatment of diabetes; CN101410957 discloses the application of resveratrol in the treatment diabetic nephropathy; But also unexposed spirulina and resveratrol composition are used for the report of prevention or treatment diabetic complication in the prior art.At present, the medicine for the treatment of diabetes has a lot, but does not but have good health care medicinal or preventive drug for diabetic complication.
Summary of the invention
In order to solve the problems of the technologies described above, the invention provides and a kind ofly can replenish health nutrition, make nutritive equilibrium, reduce fasting glucose, improve carbohydrate tolerance; Can prevent or treat resveratrol and Spirulin composition and preparation and the method for making of the diseases such as diabetes and complication thereof.
The concrete technical scheme of the present invention is as follows:
The invention provides a kind of resveratrol Spirulin composition, described compositions comprises that weight portion is that spirulina and 5-30 part purity of 10-100 part is higher than high-purity resveratrol of 80%.The present invention, improves carbohydrate tolerance and fasting glucose and has good curative effect promoting islet cells to recover by a large amount of compositionss that experiment showed, described spirulina and high-purity resveratrol; And in prevention and treatment diabetes and the diseases such as complication, cardio-cerebrovascular disease thereof, has significant curative effect.
Further, resveratrol Spirulin composition of the present invention comprises that also weight portion is the Radix Astragali extract of 1-15 part, the tartary buckwheat extract of 1-15 part and the vitamin C of 0.5-3 part.The present invention has good curative effect by a large number of experiments show that high-purity resveratrol, spirulina, Radix Astragali extract, tartary buckwheat extract and ascorbic mixture to the prevent diabetes complication; Five kinds of Chinese medicine is brought into play synergism together, can promote islet cells to recover, and improves carbohydrate tolerance; Reduce blood viscosity and capillary fragility; Blood sugar lowering and blood fat, the liver protecting; Blood circulation promoting, prevention or treatment diabetes and complication and cardiovascular and cerebrovascular disease.
Further, resveratrol Spirulin composition of the present invention and adjuvant are made solid preparation, and described solid preparation comprises tablet, capsule, granule or powder; Described adjuvant comprises one or more in diluent, disintegrating agent, binding agent or the lubricant; Described diluent is selected from one or more in lactose, sorbitol, xylitol, mannitol, pregelatinized Starch, sucrose, dextrin or the microcrystalline Cellulose; Described disintegrating agent is selected from one or more in cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, polacrilin potassium, low-substituted hydroxypropyl cellulose or the hydroxyethylmethyl-cellulose; Described binding agent is selected from one or more in methylcellulose, hydroxypropyl cellulose, hypromellose, hydroxy methocel, sodium carboxymethyl cellulose, polyvidone, polyethylene glycol 6000 or the Macrogol 4000; Described lubricant is selected from one or more in magnesium stearate, micropowder silica gel, silicon dioxide, Pulvis Talci, hydrogenated vegetable oil or the sodium laurylsulfate.
Preferably, adjuvant of the present invention comprises that also weight portion is the beta-schardinger dextrin-of 1-20 part, and described beta-schardinger dextrin-is selected from one or more in glucose group-beta-cyclodextrin, HP-β-CD or the ethyl-beta-schardinger dextrin-.The adding of described beta-schardinger dextrin-and compositions form clathrate, can improve the water solublity of high-purity resveratrol and other compositions, improve simultaneously the stability of high-purity resveratrol, improve the bioavailability of solid preparation.
Further preferred, described solid preparation is tablet, and described adjuvant is hydroxy methocel, microcrystalline Cellulose, silicon dioxide and magnesium stearate, and the parts by weight of described each composition of tablet are:
Perhaps, solid preparation of the present invention is capsule, and described adjuvant is mannitol, pregelatinized Starch and cross-linking sodium carboxymethyl cellulose, and described mannitol and compositions form solid dispersion, and the parts by weight of described each composition of capsule are:
The present invention is by after making solid dispersion with compositions and mannitol, increased high-purity resveratrol in the compositions and dissolubility and the stability of other compositions, improves the bioavailability of solid preparation; Wherein the adding of pregelatinized Starch can improve the flowability of preparation, is beneficial to the mixing of supplementary material, and increases the uniformity of dosage units of solid preparation.
Further preferred, the invention provides the preparation method of described high-purity resveratrol, described method comprises take plant as feedstock purification and forming, and described plant is selected from Semen Vitis viniferae skin slag, Semen arachidis hypogaeae, Rhizoma Polygoni Cuspidati, and described method of purification is a kind of in the following method:
Semen Vitis viniferae skin ground-slag is broken, add the 70%-90% alcohol reflux 3 times, the amount that adds ethanol for the first time is 5-10 times of Semen Vitis viniferae skin slag, backflow 3-5h, the amount that adds for the second time ethanol is 3-6 times of Semen Vitis viniferae skin slag, backflow 2-4h, the amount that adds for the third time ethanol is 1-3 times of Semen Vitis viniferae skin slag, backflow 1-3h, merge backflow, filter, it is 70 ℃ of thick pastes that relative density is 1.30-1.32 that filtrate is concentrated into temperature, the dry Semen Vitis viniferae skin slag extract that gets; Semen Vitis viniferae skin slag extract is dissolved in the sodium bicarbonate aqueous solution of 1-5%, stir 20-50min, sediment separate out washes precipitate to neutrality with water, then precipitate is added in the water that 10-15 doubly measures, in 85-90 ℃ of dissolving, aqueous solution slowly is cooled to 10-25 ℃, leaves standstill, wash out precipitation, lyophilization makes purity and is higher than 90% resveratrol;
Or with the Testa arachidis hypogaeae crushed after being dried, Testa arachidis hypogaeae after pulverizing is carried out supercritical carbon dioxide extraction, with dehydrated alcohol and propanol as entrainer, Testa arachidis hypogaeae, entrainer, the mass ratio of the circulation consumption of carbon dioxide hourly is 1:0-0.2:10-30, extractor pressure is 6-15Mpa, and temperature is 40-55 ℃, and knockout drum pressure is 3.5-6.5Mpa, temperature is 20-25 ℃, extraction time 2-3h collects extract, and is concentrated, with macroporous resin adsorption post on the concentrated solution, ethanol with 25%-30% carries out eluting, collects eluent, and concentrate drying gets purity and is higher than 90% resveratrol;
Or with the Rhizoma Polygoni Cuspidati pulverizing, with 75-95% soak with ethanol 5h, reflux, extract, twice again, and the amount that adds ethanol for the first time is 5-10 times of Rhizoma Polygoni Cuspidati, backflow 2-4h, and the amount that adds ethanol for the second time is 2-5 times of Rhizoma Polygoni Cuspidati, backflow 1-3h merges backflow, filters, and is condensed into thick paste; Be that 1:50 adds water with volume ratio by weight with thick paste, ultrasonic dissolution filters, and inclining supernatant, adds 3-5 ethyl acetate extraction doubly three times, combined ethyl acetate liquid, and regulating pH value with dilute alkaline soln is 8-9, concentrated, gets the resveratrol crude product; The resveratrol crude product is dissolved in upper macroporous resin column in the ethanol of 2 times of amounts, be eluted to eluent with distilled water first and be colourless, be 50% ethanol eluting again with concentration, collect eluent, concentrated, be the mixed liquor recrystallization of 5:2 with ethanol and ethyl acetate volume ratio, obtain purity and be higher than 90% resveratrol;
Perhaps described high-purity resveratrol is prepared from by following any chemical synthesis process:
Be raw material with 3,5-dimethoxy benzaldehyde, under the catalysis of highly basic, carry out condensation reaction with PARA METHOXY PHENYL ACETONITRILE, form 3,4 ', 5-trimethoxy stilbene nitrile, through hydrolysis, make 3,4 ' again, the acid of 5-trimethoxy stilbene, under the catalysis of Cu, carry out decarboxylic reaction and obtain trans-3,4 ', 5-trimethoxy stilbene obtains purity by demethylating reaction at last and is higher than 98% resveratrol under the catalysis of Boron tribromide;
Or with 3, the 5-3,5-dimethoxybenzoic alcohol is raw material, make 3 with the Lucas reagent reaction, 5-dimethoxy benzyl chlorine, make 3,5-dimethoxy-benzyl diethyl phosphonate with the NSC 5284 reaction again, under the catalysis of sodium alkoxide, make (E)-3 with P-methoxybenzal-dehyde again, 4 ', 5-trimethoxy stilbene is at last at AlCl
3Effect under demethylation make purity and be higher than 98% resveratrol;
Or with 4-hydroxyl phenylacetic acid and 3, the 5-4-dihydroxy benzaldehyde is raw material, make (E)-2-(4 '-hydroxy phenyl through perkin reaction)-3-(3 ', 5 '-dihydroxy phenyl)-acrylic acid, carry out again decarboxylation, isomerization reaction makes purity and is higher than 98% resveratrol.
The wide material sources of high-purity resveratrol of the present invention as can be known from above method, this shows for the prevention of diabetes and cardiovascular and cerebrovascular disease and complication thereof and treats the restriction that can not receive again medicament sources, and, high-purity resveratrol that described method obtains all has very high purity, impurity level is few relatively, the described compositions safety of making, few side effects.
The preparation method of described Radix Astragali extract provided by the invention is: Radix Scutellariae is pulverized, is decocted with water three times, for the first time water consumption be astragalus weight 10-15 doubly, decocted 2-3 hour, the second water consumption be astragalus weight 5-10 doubly, decocted 1-2 hour, water consumption is 2-5 times of astragalus weight for the third time, decocted 1-2 hour, collecting decoction filters, and filtrate is concentrated, drying makes Radix Astragali extract;
The preparation method of the described tartary buckwheat extract that provides is: Radix Et Rhizoma Fagopyri Tatarici is pulverized, added the 75%-80% alcohol reflux 3 times, the amount that adds ethanol for the first time is 10-15 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 2-5h, the amount that adds for the second time ethanol is 5-10 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 1-3h, and the amount that adds for the third time ethanol is 2-3 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 1-3h, merge backflow, filter, filtrate is concentrated, drying makes tartary buckwheat extract.
The present invention also provides the preparation method of described solid preparation on the other hand.
When described solid preparation was tablet, described method comprised the steps:
1) spirulina pulverizing, vitamin C are pulverized, with high-purity resveratrol, Radix Astragali extract and tartary buckwheat extract mix homogeneously, crossed the 40-60 mesh sieve, make the resveratrol Spirulin composition;
2) beta-schardinger dextrin-is added in the water that 2-5 doubly measures, fully be ground to water quantities and be less than 5% pastel, grind the lower described resveratrol Spirulin composition of step 1) that adds, mix homogeneously, lyophilization makes clathrate;
3) with clathrate and microcrystalline Cellulose, hydroxy methocel, mix homogeneously makes mixture, granulates, and adds silicon dioxide and magnesium stearate, mix homogeneously, tabletting again.
When described solid preparation was capsule, described method comprised the steps:
1) gets described resveratrol Spirulin composition;
2) mannitol is placed the water-bath heating and melting, make fused mass, stir the lower resveratrol Spirulin composition that adds, mix homogeneously is crossed the 100-120 mesh sieve, makes solid dispersion;
3) with solid dispersion and pregelatinized Starch and cross-linking sodium carboxymethyl cellulose mix homogeneously, make mixture;
4) described mixture is packed in No. 0 capsule, make capsule.
It is high that resveratrol Spirulin composition of the present invention has stability, the high beneficial effect that waits of bioavailability; Described resveratrol Spirulin composition and adjuvant are made solid preparation, described adjuvant comprises the adjuvants such as microcrystalline Cellulose, hydroxy methocel, beta-schardinger dextrin-, described beta-schardinger dextrin-and resveratrol Spirulin composition form clathrate, it has increased dissolubility and the stability of each composition in the compositions, has improved stability and the bioavailability of solid preparation; Described resveratrol Spirulin composition and solid preparation thereof improve carbohydrate tolerance promoting islet cells to recover; Reduce blood viscosity and capillary fragility, blood circulation promoting; Blood sugar lowering and blood fat, the liver protecting; Prevention or treatment diabetes and the diseases such as complication and cardiovascular and cerebrovascular disease thereof have good therapeutic effect.
Description of drawings
Fig. 1 resveratrol spirulina tablet is on the impact of normal glucose tolerance in mice;
Fig. 2 resveratrol spirulina tablet is on the impact of hyperglycemia model glucose tolerance in mice;
Resveratrol spirulina tablet 0.25,0.5,1.5 be respectively 5,10,30 times of the human body recommended amounts as low (0.25g/kg BW), in (0.50g/kg BW) and high (1.5g/kg BW) 3 dosage.
The specific embodiment
Embodiment 1
| Compositions | Consumption (g) |
| Spirulina | 40 |
| High-purity resveratrol | 17 |
Preparation method:
1) preparation of high-purity resveratrol: with the Testa arachidis hypogaeae crushed after being dried, Testa arachidis hypogaeae after pulverizing is carried out supercritical carbon dioxide extraction, with dehydrated alcohol and propanol as entrainer, Testa arachidis hypogaeae, entrainer, the mass ratio of the circulation consumption of carbon dioxide hourly is 1:0.1:20, extractor pressure is 10Mpa, and temperature is 50 ℃, and knockout drum pressure is 5Mpa, temperature is 20 ℃, extraction time 3h collects extract, and is concentrated, with macroporous resin adsorption post on the concentrated solution, ethanol with 30% carries out eluting, collects eluent, and it is high-purity resveratrol of 95% that concentrate drying gets purity;
2) spirulina is pulverized, with high-purity resveratrol mix homogeneously, crossed 50 mesh sieves, make the resveratrol Spirulin composition.
Embodiment 2
| The composition of compositions | Consumption (g) |
| Spirulina | 10 |
| High- |
5 |
| Radix Astragali extract | 1 |
| Tartary buckwheat extract | 1 |
| Vitamin C | 0.5 |
Preparation method:
1) preparation of high-purity resveratrol: Semen Vitis viniferae skin ground-slag is broken, add 90% alcohol reflux 3 times, the amount that adds ethanol for the first time is 5 times of Semen Vitis viniferae skin slag, backflow 5h, the amount that adds for the second time ethanol is 6 times of Semen Vitis viniferae skin slag, backflow 2h, the amount that adds for the third time ethanol is 1 times of Semen Vitis viniferae skin slag, backflow 3h, merge backflow, filter, it is that 70 ℃ of relative densities are 1.30 thick paste that filtrate is concentrated into temperature, the dry Semen Vitis viniferae skin slag extract that gets; Semen Vitis viniferae skin slag extract is dissolved in 1% the sodium bicarbonate aqueous solution, stir 50min, sediment separate out washes precipitate to neutrality with water, then precipitate is added in the water of 10 times of amounts, in 90 ℃ of dissolvings, aqueous solution slowly is cooled to 25 ℃, leaves standstill, wash out precipitation, lyophilization makes purity and is 98% resveratrol;
2) preparation of Radix Astragali extract: Radix Scutellariae is pulverized, decocted with water three times, water consumption is 15 times of astragalus weight for the first time, decocted 2 hours, the second water consumption is 10 times of astragalus weight, decocts 1 hour, and water consumption is 5 times of astragalus weight for the third time, decocted 1 hour, collecting decoction filters, and filtrate is concentrated, drying makes Radix Astragali extract;
3) preparation of tartary buckwheat extract: Radix Et Rhizoma Fagopyri Tatarici is pulverized, added 80% alcohol reflux 3 times, the amount that adds ethanol for the first time is 10 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 5h, the amount that adds for the second time ethanol is 10 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 1h, and the amount that adds for the third time ethanol is 3 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 1h, merge backflow, filter, filtrate is concentrated, drying makes tartary buckwheat extract;
4) spirulina pulverizing, vitamin C are pulverized, with high-purity resveratrol, Radix Astragali extract and tartary buckwheat extract mix homogeneously, crossed 60 mesh sieves, make the resveratrol Spirulin composition.
Embodiment 3
| The composition of solid preparation | Consumption (g) |
| Spirulina | 100 |
| High-purity resveratrol | 30 |
| Radix Astragali |
15 |
| |
15 |
| Vitamin C | 3 |
| |
20 |
| |
5 |
| Low-substituted hydroxypropyl cellulose | 12 |
| |
5 |
| |
5 |
| Hydrogenated |
5 |
Preparation method:
1) preparation of high-purity resveratrol: with 3 of 0.01mol, the PARA METHOXY PHENYL ACETONITRILE of 5-dimethoxy benzaldehyde and 0.01mol is dissolved in the 10ml ethanol, adds the sodium metal of 0.02mol, 75 ℃ of backflow 12h, cooling, crystallize out, make 3,4 ', 5-trimethoxy stilbene nitrile, with 3,4 ', 5-trimethoxy stilbene nitrile is dissolved in the ethylene glycol, adds sodium hydroxide 0.3mol, stir, 130 ℃ of reactions, add again the dilute hydrochloric acid acidify, should make 3 through the side of hydrolysis, 4 ', the acid of 5-trimethoxy stilbene under the catalysis of Cu, is carried out decarboxylic reaction in 200 ℃ in quinoline, obtain trans-3,4 ', 5-trimethoxy stilbene is under the catalysis of Boron tribromide, carry out demethylating reaction in 30 ℃, obtain purity and be 99% resveratrol;
2) preparation of Radix Astragali extract: Radix Scutellariae is pulverized, decocted with water three times, water consumption is 10 times of astragalus weight for the first time, decocted 3 hours, the second water consumption is 5 times of astragalus weight, decocts 2 hours, and water consumption is 2 times of astragalus weight for the third time, decocted 2 hours, collecting decoction filters, and filtrate is concentrated, drying makes Radix Astragali extract;
3) preparation of tartary buckwheat extract: Radix Et Rhizoma Fagopyri Tatarici is pulverized, added 75% alcohol reflux 3 times, the amount that adds ethanol for the first time is 15 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 2h, the amount that adds for the second time ethanol is 5 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 3h, and the amount that adds for the third time ethanol is 2 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 3h, merge backflow, filter, filtrate is concentrated, drying makes tartary buckwheat extract;
4) spirulina pulverizing and vitamin C are pulverized, with high-purity resveratrol, Radix Astragali extract and tartary buckwheat extract mix homogeneously, cross 40 mesh sieves, make the resveratrol Spirulin composition;
5) with resveratrol Spirulin composition and sorbitol, sucrose, low-substituted hydroxypropyl cellulose, methylcellulose, hydroxypropyl cellulose and hydrogenated vegetable oil mix homogeneously, make mixture, granulate, make granule, every heavily about 0.25g.
Embodiment 4
| The composition of solid preparation | Consumption (g) |
| Spirulina | 35 |
| High-purity resveratrol | 13 |
| Radix Astragali extract | 2.5 |
| Tartary buckwheat extract | 2.5 |
| Vitamin C | 0.75 |
| Xylitol | 8 |
| Dextrin | 2 |
| Polyvinylpolypyrrolidone | 4 |
| Hypromellose | 3 |
| Macrogol 4000 | 3 |
Preparation method:
1) preparation of high-purity resveratrol: Rhizoma Polygoni Cuspidati is pulverized, and with 80% soak with ethanol 5h, reflux, extract, twice again, and the amount that adds ethanol for the first time is 10 times of Rhizoma Polygoni Cuspidati, backflow 2h, the amount that adds ethanol for the second time is 2 times of Rhizoma Polygoni Cuspidati, backflow 3h, merge backflow, filter, be condensed into thick paste; Be that 1:50 adds water with volume ratio by weight with thick paste, ultrasonic dissolution filters, and inclining supernatant, adds 5 times ethyl acetate extraction three times, combined ethyl acetate liquid, and regulating pH value with dilute alkaline soln is 8, concentrates, and gets the resveratrol crude product; The resveratrol crude product is dissolved in upper macroporous resin column in the ethanol of 2 times of amounts, be eluted to eluent with distilled water first and be colourless, be 50% ethanol eluting again with concentration, collect eluent, concentrated, be the mixed liquor recrystallization of 5:2 with ethanol and ethyl acetate volume ratio, obtain purity and be high-purity resveratrol of 96%;
2) preparation of Radix Astragali extract: Radix Scutellariae is pulverized, decocted with water three times, water consumption is 10 times of astragalus weight for the first time, decocted 3 hours, the second water consumption is 5 times of astragalus weight, decocts 2 hours, and water consumption is 2 times of astragalus weight for the third time, decocted 2 hours, collecting decoction filters, and filtrate is concentrated, drying makes Radix Astragali extract;
3) preparation of tartary buckwheat extract: Radix Et Rhizoma Fagopyri Tatarici is pulverized, added 75% alcohol reflux 3 times, the amount that adds ethanol for the first time is 15 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 2h, the amount that adds for the second time ethanol is 5 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 3h, and the amount that adds for the third time ethanol is 2 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 3h, merge backflow, filter, filtrate is concentrated, drying makes tartary buckwheat extract;
4) spirulina pulverizing and vitamin C are pulverized, with high-purity resveratrol, Radix Astragali extract and tartary buckwheat extract mix homogeneously, cross 50 mesh sieves, make the resveratrol Spirulin composition;
5) with resveratrol Spirulin composition and xylitol, dextrin, polyvinylpolypyrrolidone, hypromellose and Macrogol 4000, mix homogeneously is made powder.
| The composition of solid preparation | Consumption (g) |
| Spirulina | 50 |
| High-purity resveratrol | 10 |
| Radix Astragali extract | 10 |
| Tartary buckwheat extract | 10 |
| Vitamin C | 2 |
| HP-β- |
5 |
| Hydroxy methocel | 10 |
| Microcrystalline Cellulose | 10 |
| Silicon dioxide | 2.5 |
| Magnesium stearate | 0.5 |
Preparation method:
1) preparation of high-purity resveratrol: Semen Vitis viniferae skin ground-slag is broken, add 80% alcohol reflux 3 times, the amount that adds ethanol for the first time is 7 times of Semen Vitis viniferae skin slag, backflow 4h, the amount that adds for the second time ethanol is 5 times of Semen Vitis viniferae skin slag, backflow 3h, the amount that adds for the third time ethanol is 2 times of Semen Vitis viniferae skin slag, backflow 2h, merge backflow, filter, it is that 70 ℃ of relative densities are 1.31 thick paste that filtrate is concentrated into temperature, the dry Semen Vitis viniferae skin slag extract that gets; Semen Vitis viniferae skin slag extract is dissolved in 1% the sodium bicarbonate aqueous solution, stir 50min, sediment separate out washes precipitate to neutrality with water, then precipitate is added in the water of 10 times of amounts, in 90 ℃ of dissolvings, aqueous solution slowly is cooled to 25 ℃, leaves standstill, wash out precipitation, lyophilization makes purity and is high-purity resveratrol of 93%;
2) preparation of Radix Astragali extract: Radix Scutellariae is pulverized, decocted with water three times, water consumption is 12 times of astragalus weight for the first time, decocted 2 hours, the second water consumption is 7 times of astragalus weight, decocts 1 hour, and water consumption is 3 times of astragalus weight for the third time, decocted 1 hour, collecting decoction filters, and filtrate is concentrated, drying makes Radix Astragali extract;
3) preparation of tartary buckwheat extract: Radix Et Rhizoma Fagopyri Tatarici is pulverized, added 80% alcohol reflux 3 times, the amount that adds ethanol for the first time is 12 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 3h, the amount that adds for the second time ethanol is 7 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 2h, and the amount that adds for the third time ethanol is 2 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 2h, merge backflow, filter, filtrate is concentrated, drying makes tartary buckwheat extract;
4) spirulina pulverizing and vitamin C are pulverized, with high-purity resveratrol, Radix Astragali extract and tartary buckwheat extract mix homogeneously, cross 50 mesh sieves, make the resveratrol Spirulin composition;
5) HP-β-CD is added in the water of 2 times of amounts, fully be ground to water quantities and be less than 5% pastel, grind the lower described resveratrol Spirulin composition of step 4) that adds, mix homogeneously, lyophilization makes clathrate;
6) with clathrate and microcrystalline Cellulose, hydroxy methocel, mix homogeneously makes mixture, granulates, and adds silicon dioxide and magnesium stearate again, mix homogeneously, tabletting, every heavily about 0.25g.
Embodiment 6
| The composition of solid preparation | Consumption (g) |
| Spirulina | 60 |
| High- |
15 |
| |
5 |
| |
5 |
| Vitamin C | 1 |
| The glucose group-beta-cyclodextrin | 10 |
| |
5 |
| |
5 |
| Silicon dioxide | 1 |
| Magnesium stearate | 1 |
Preparation method: make tablet by embodiment 5 described methods, every heavily about 0.3g.
Embodiment 7
| The composition of solid preparation | Consumption (g) |
| Spirulina | 55 |
| High-purity resveratrol | 12 |
| Radix Astragali extract | 7.5 |
| Tartary buckwheat extract | 7.5 |
| Vitamin C | 1.5 |
| The glucose group-beta- |
5 |
| Ethyl-beta-schardinger dextrin- | 2 |
| Pregelatinized Starch | 10 |
| Polacrilin potassium | 10 |
| Polyethylene glycol 6000 | 5 |
| Micropowder silica gel | 0.8 |
Preparation method: make tablet by embodiment 5 described methods, every heavily about 0.24g.
Embodiment 8
| The composition of solid preparation | Consumption (g) |
| Spirulina | 80 |
| High- |
25 |
| Radix Astragali extract | 12.5 |
| Tartary buckwheat extract | 12.5 |
| Vitamin C | 2.5 |
| HP-β- |
20 |
| Lactose | 10 |
| Polyvidone | 10 |
| |
5 |
| Hydroxyethylmethyl- |
5 |
Preparation method:
1) preparation of high-purity resveratrol: with 0.1mol3, the Lucas reagent of 5-3,5-dimethoxybenzoic alcohol and 0.15mol at room temperature drops in the reactor, reacts 1 hour, make mixed liquor, with the mixed liquor sucking filtration, get white solid, again with distillation washing 3 times, reaction makes 3,5-dimethoxy benzyl chlorine, the NSC 5284 with 0.2mol is dissolved in the ethanol again, back flow reaction 3 hours, make 3,5-dimethoxy-benzyl diethyl phosphonate is dissolved in dry N with 3,5-dimethoxy-benzyl diethyl phosphonate, in the dinethylformamide, stir lower DMF solution with P-methoxybenzal-dehyde and splash in the mentioned solution, ice bath is cooled to 5 ℃, adds Feldalat NM, keeping 5 ℃ reacts completely, make (E)-3,4 ', 5-trimethoxy stilbene, with (E)-3,4 ', 5-trimethoxy stilbene is dissolved in the 20ml pyridine, slowly splashes into AlCl
3, carry out demethylating reaction, making purity is 99.5% resveratrol;
2) preparation of Radix Astragali extract: prepare Radix Astragali extract by embodiment 5 described methods;
3) preparation of tartary buckwheat extract: prepare tartary buckwheat extract by embodiment 5 described methods;
4) HP-β-CD is added in the water of 3 times of amounts, fully be ground to water quantities and be less than 5% pastel, grind the lower described compositions of step 1) that adds, mix homogeneously, lyophilization makes clathrate;
5) with clathrate and lactose, polyvidone, sodium carboxymethyl cellulose and hydroxyethylmethyl-cellulose, mix homogeneously makes mixture, and in No. 0 capsule of packing into, every capsule is 0.35g heavily approximately.
Embodiment 9
| The composition of solid preparation | Consumption (g) |
| Spirulina | 70 |
| High- |
20 |
| Radix Astragali extract | 12 |
| Tartary buckwheat extract | 12 |
| Vitamin C | 1.5 |
| |
20 |
| |
15 |
| Cross-linking sodium carboxymethyl cellulose | 8 |
Preparation method:
1) prepares the resveratrol Spirulin composition by embodiment 5 described methods;
2) mannitol is placed the water-bath heating and melting, make fused mass, stir the lower resveratrol Spirulin composition that adds, mix homogeneously is crossed 120 mesh sieves, makes solid dispersion;
3) with solid dispersion and pregelatinized Starch and cross-linking sodium carboxymethyl cellulose mix homogeneously, make mixture;
4) described mixture is packed in No. 0 capsule, make capsule, every capsule is 0.21g heavily approximately.
The test of test example 1 study on the stability
With the described resveratrol Spirulin composition of embodiment of the invention 5-9 and preparation thereof, requirement by accelerated test in two appendix XIXC of Chinese Pharmacopoeia medicine stability test guideline, being positioned over relative humidity is 60% ± 5%, temperature is in 40 ℃ ± 2 ℃ the constant incubator, in 0,1,3, June and December, the sampling index of carrying out Resveratrol content (quite labelled amount) % of solid preparation of the present invention checks respectively, and result of the test sees Table 1.
The study on the stability result of the test of the described solid preparation of table 1 embodiment 5-9
As can be seen from the table, resveratrol Spirulin composition of the present invention and preparation thereof have very high stability for the environment of high humidity and Gao Re, and the character of described solid preparation does not change yet.
Test example 2 animal experiments
1 material
1.1 sample uses the embodiment of the invention 5 described resveratrol spirulina tablets (BS), face the time spent grind into powder, with distilled water be mixed with 0.025, the tested suspension of 0.05g/mL and 0.15g/mL concentration, be respectively 5,10,30 times of the human body recommended amounts as low (0.25g/kg BW), in (0.50g/kg BW) and high (1.5g/kg BW) 3 dosage;
1.2 the positive reference substance metformin hydrochloride, Shanghai Pharmaceutical Group company limited letter friendship pharmacy head factory, lot number: 061128, face the time spent grind into powder, be mixed with the suspension of 0.025g/mL with distilled water;
1.3 the test of laboratory animal blood sugar lowering is with cleaning the level Male Kunming strain mice, five ages in week, body weight 26.0 ± 2.0g; Safety experiment is with a cleaning level Kunming mouse, age all around, body weight 20.0 ± 2.0g; All (quality certification number: the moving word 14-001 of doctor), all animals conform and are used for test behind the 5d available from Lanzhou Inst. of Biological Products, Ministry of Public Health;
1.4 main agents alloxan (Alloxan, ALX), U.S. Sigma company product faces the time spent is mixed with 2.5mg/mL with normal saline solution bottle; Glucose (AR), Beijing Chemical Plant, lot number: 020513;
1.5 the auspicious special blood glucose monitoring system Blood Glucose Monitoring System of instrument: Huaguang Biotechnology Co., Ltd., number of registration: state's food medicine prison tool (being permitted) word 2005 the 2400058th; Comprise auspicious special Rightest
TMBlood glucose meter, auspicious special Rightest
TMDetector bar seat, auspicious special Rightest
TMQC liquid, auspicious special Rightest
TMThe QC detection lug; Auspicious special Rightest
TMDetector bar: Huaguang Biotechnology Co., Ltd., number of registration: state's food medicine prison tool (being permitted) word 2005 the 2400046th, lot number: 1169062; 721 spectrophotometers, Shanghai the 3rd analytical tool factory; The SW-CJ-1F superclean bench, 58X is two-sided, Suzhou Decontamination Equipment Plant; JA-2003 type one thousandth electronic balance, Shanghai Precision Scientific Apparatus Co., Ltd; DT-type electronic balance, Changshu City's weighing apparatus factory;
1.6 experiment place Gansu Prov. Medical Science Research Inst. Experimental Animal Center, the experimental situation quality certification number: SYXK[is sweet] 2006-0010 number.
2 methods
2.1 the mice of body weight 24～28g is selected in the foundation of hyperglycemia model, after water 24h is can't help in fasting, with freshly prepared alloxan with BW3 every other day intravenous injection of 25mg/kg, accumulated dose 75mg/kg BW; The rear 7d of first injection, fasting 3h surveys blood glucose, and the mice of screening blood glucose value 10～25mmol/L is hyperglycemia model success animal;
2.2 carbohydrate tolerance test
2.2.1 20 of the mices of body weight 24～28g are selected in the normal mouse carbohydrate tolerance test, are divided at random blank group and BS organizes 10 every group by blood sugar level and body weight; Water 3h is can't help in fasting, and the BS group gives the BS of 0.15g/mL by 0.1mL/10g BW gavage, and blank group waits the distilled water of capacity; Behind the 20min, give the glucose solution of freshly prepared 0.1g/mL by 0.2mL/10g BW gavage, get the tail hematometry to glucose after 0, the blood glucose value of 0.5h and 2h, calculate to day part Area under the curve of blood glucose behind the glucose, as the carbohydrate tolerance observation index; The calculating of Area under the curve of blood glucose:
Area under the curve of blood glucose=0.25 * (0h blood glucose value+4 * 0.5h blood glucose value+3 * 2h blood glucose value);
2.2.2 hyperglycemia model success animal is selected in the model mice carbohydrate tolerance test, is divided at random 5 groups by blood sugar level and body weight, is respectively BS basic, normal, high three dosage groups, positive controls and model control group; Fasting is the same, basic, normal, high three the dosage groups of BS by 0.1mL/10gBW respectively gavage give 0.025, the BS of 0.05g/mL and 0.15g/mL; Positive controls gives 0.025g/mL metformin hydrochloride suspension; Model control group waits the distilled water of capacity; Determination method of blood sugar and Area under the curve of blood glucose calculate same 2.2.1;
2.3 blood sugar lowering test
2.3.1 20 mices are selected in the test of normal mouse blood sugar lowering, water 3h is can't help in fasting, gets tail blood and surveys blood glucose value, is divided at random blank group and BS group, 10 every group by blood sugar level and body weight; The BS group gives the BS of 0.15g/mL by 0.1mL/10g BW gavage, blank group waits the distilled water of capacity, once a day, and continuous gavage 30d; During off-test, water 24h is can't help in fasting, gets tail blood and surveys fasting blood sugar, calculates blood glucose decline percentage rate:
Blood glucose value * 100% before blood glucose decline percentage rate=(blood glucose value after blood glucose value before the test-test)/test;
2.3.2 hyperglycemia model success animal is selected in the test of model mice blood sugar lowering, grouping and the same 2.2.2 of gavage amount, once a day, continuous gavage 30d; Blood sugar detection and blood glucose decline percentage rate calculate same 2.3.1;
2.4 on mice organs affect the blood sugar lowering off-test after, put to death experiment mice, perusal and dissection have or not obvious pathological changes, take by weighing liver,kidney,spleen, thymic weight, calculate the ratio (with 100 gram body weight calculating) of corresponding organ weights and body weight (dirty/the body ratio):
2.5 the chmice acute toxicity test is through trial test LD
50Value can't record, and carries out the maximum tolerance determination experiment; Get 20 of body weight 18～22g mices, male and female half and half, fasting be can't help after water spends the night, and gives (human body recommended amounts 360 times), every minor tick 4h BS3 time by Cmax 0.3g/mL, maximum gavage amount 0.2mL/10g gavage; Observe general signs, poisoning symptom and the death toll of mice, and respectively claim the weight of animals once in 3d, 7d and 14d; Put to death mice behind the 14d, the main organs such as dissection, its heart of perusal, liver,spleen,kidney; Calculate maximum tolerated dose (MTD) according to the maximum tolerated dose method;
2.6 experimental data that statistical analysis is surveyed all with
Expression, the data SPSS10.0 statistical software processes, and organizes the relatively employing method of analysis of variance of mean more; Two groups of means relatively adopt the t check.
3 results
3.1 alloxan causes the foundation of hyperglycemia model
After the modeling of mouse mainline alloxan, selecting the animal of blood glucose between 10～25mmol/L scope is the hyperglycemia model animal; Its blood glucose value is minimum to be 10.2mmol/L, is up to 18.6mmol/L, and meansigma methods is 12.0mmol/L; Compare with blank group 7.0mmol/L, fasting glucose obviously raises, and learns by statistics and processes, and there is utmost point significance (P＜0.01) in difference, shows the hyperglycemia model establishment, the results are shown in Table 2;
Table 2 hyperglycemia model is set up
3.2BS the impact on Mouse Weight
After the continuous gavage of normal mouse gave the BS30d of 1.50g/kg BW, body weight increased gradually, compared with the blank group, and no significant difference (P＞0.05) shows that BS to normal Mouse Weight not statistically significant, the results are shown in Table 3;
Table 3BS is on the impact of normal Mouse Weight
The hyperglycemia model mice give 0.25,0.50 and the BS30d of 1.50g/kg BW after, Mouse Weight increases gradually, compare with matched group and metformin group, difference is not significantly (P＞0.05) all, show that each dosage group of BS affects without significance alloxan hyperglycemia model Mouse Weight, the results are shown in Table 4;
Table 4BS is on the impact of hyperglycemia model Mouse Weight
3.3BS the impact on the mice fasting glucose
After the continuous gavage of normal mouse gave the BS30d of 1.50g/kg BW, the blood sugar lowering rate was 2.84%, compared with blank group 3.09%, processed by statistics, and no significant difference (p＞0.05) shows that BS to normal mouse fasting glucose no difference of science of statistics, the results are shown in Table 5;
Table 5BS affects the normal mouse fasting glucose
Annotate:
aP＞0.05 is with relatively blank
The continuous gavage of hyperglycemia model mice gives 0.25,0.50, behind the BS30d of 1.50g/kg BW, each dosage group blood sugar lowering rate and matched group relatively: dosage is the BS(P＜0.01 of 0.25g/kg BW), the BS(P of 0.50g/kg BW＜0.01) and the BS(P of 1.50g/kg BW＜0.01) all have a significant difference; Metformin and matched group compare, and difference is (P＜0.01) extremely significantly; Each dosage group blood sugar lowering rate of BS and metformin compare: the BS no significant difference of 0.25g/kg BW, 0.50g/kg BW (P＞0.05), the BS significant difference of 1.50g/kg BW (P＜0.05); Show that BS dosage is that 0.25g/kg BW, 0.50g/kg BW, 1.50g/kg BW all cause the hyperglycemia mice to alloxan and have and reduce the fasting glucose effect, and the BS of 0.25g/kg BW, 0.50g/kg BW dosage is close with the hypoglycemic activity of metformin, and the hypoglycemic activity of the BS of 1.50g/kg BW dosage is better than metformin; The results are shown in Table 6;
Table 6BS is on the impact of hyperglycemia model mice fasting glucose
Annotate:
aP＜0.01,
bP＜0.01,
cP＜0.01 and compares;
dP＜0.05,
fCompare with metformin P＞0.05;
3.4BS the impact on glucose tolerance in mice
BS sees Fig. 1 to the impact of normal glucose tolerance in mice;
The carbohydrate tolerance experimental result that the normal mouse gavage gives 1.50g/kgBW BS shows: blood sugar increasing is to 14.0mmol/L during 0.5h, 2h blood glucose is down to 5.4mmol/L, Area under the curve of blood glucose is 21.9, compare with blank 19.7, no significant difference (P＞0.05), show BS on normal glucose tolerance in mice without impact; The results are shown in Table 7;
Table 7BS is on the impact of normal glucose tolerance in mice
Annotate:
aP＞0.05 is with relatively blank
BS sees Fig. 2 to the impact of hyperglycemia model glucose tolerance in mice;
After each dosage group of hyperglycemia model animal gives BS, the blood glucose value of each time point all is lower than matched group, Area under the curve of blood glucose with compare: the BS of 0.25g/kgBW and the BS of 0.50g/kgBW group has significant difference (P＜0.05), and the BS of 1.50g/kgBW has utmost point significant difference (P＜0.01); Metformin with compare difference extremely significantly (P＜0.01); Each dosage of BS and metformin be relatively: 0.25,0.50 and the BS of 1.50g/kgBW there are no significant difference (P＞0.05); Show BS0.25,0.50 and 1.50g/kgBW dosage all alloxan is caused the hyperglycemia model mice effect that strengthens carbohydrate tolerance is arranged, and the BS of described dosage is close on the impact of carbohydrate tolerance with metformin; The results are shown in Table 8;
Table 8BS is on the impact of hyperglycemia model glucose tolerance in mice
Annotate:
aP＜0.05,
bP＜0.05,
cP＜0.01 and compares;
dCompare with metformin P＞0.05;
3.5BS the impact on mice organs
After the continuous gavage of normal mouse gave the BS30d of 1.50g/kg BW, each dirty/body was than comparing with blank, and no significant difference (P＞0.05) shows BS to the equal not statistically significant of normal Organs of Mice, the results are shown in Table 9;
Table 9BS is on the impact of normal mice organs
The continuous gavage of hyperglycemia model mice give 0.25,0.50 and the BS30d of 1.50g/kgBW after, each dosage group with compare, each is dirty/and body is than there are no significant difference (P＞0.05), shows BS to the equal zero difference significance of hyperglycemia model Organs of Mice, the results are shown in Table 10;
Table 10BS is on the impact of hyperglycemia model mice organs
3.6BS acute toxicity testing BS with Cmax 0.3g/mL and maximum gavage capacity 0.2mL/10g, give mouse stomach 3 times in the 24h after, every minor tick 4h; Animal appearance, behavior, ingest, drain, be showed no unusual, body weight increases gradually, without animal dead; Behind the 14d, put to death mice, dissect the main organs no abnormality seens such as its heart of perusal, liver,spleen,kidney; The maximum tolerated dose that mouse stomach gives BS is 18.0g/kg BW, is 360 times of human body recommended amounts; Show that BS toxicity is low, clinical recommendation consumption safety the results are shown in Table 11;
Table 11BS acute toxicity testing
Show by test, resveratrol Spirulin composition of the present invention and preparation thereof are to the body weight of normal model mice, fasting glucose, carbohydrate tolerance, the body weight of internal organs and hyperglycemia model mice, internal organs and matched group relatively there are no significant difference, show resveratrol Spirulin composition of the present invention and preparation thereof on normal mouse model without impact, but the alternative fasting glucose amount that reduces the hyperglycemia model mice, strengthen the carbohydrate tolerance of hyperglycemia model mice, in the anxious poison test of carrying out, described resveratrol Spirulin composition and preparation adopt maximum tolerated dose when being 360 times of human body recommended amounts, observe the heart of mice, liver, spleen, the main organs no abnormality seens such as kidney show the almost non-toxic side effect of resveratrol Spirulin composition and preparation thereof.
Test example 3
Test example 50 routine diabeticss, trial edition inventive embodiments 5 described resveratrol spirulina tablets, prove the curative effect of resveratrol Spirulin composition of the present invention and preparation thereof by detecting insulin, fasting glucose, the red albumin of saccharifying, glyceric acid fat and cholesterol indices, the curative effect that described indices is treated after front and the treatment relatively sees Table 12.
Curative effect before and after the treatment of table 12 indices relatively
| Index | Before the treatment (mmol/L) | After the treatment (mmol/L) |
| Insulin | 9.52±3.81 | 13.26±3.46 |
| Fasting glucose | 10.12±4.17 | 6.48±3.19 |
| The red albumin of saccharifying | 14.3±4.20 | 10.29±3.84 |
| Glyceric acid fat | 3.30±1.80 | 2.61±0.85 |
| Cholesterol | 8.12±2.45 | 6.43±2.05 |
Try out as can be seen from the table the diabetics of resveratrol Spirulin composition of the present invention and preparation thereof, each patient is reflected respond well, the experimenter is in high spirits, do not feel sleepy, strong and easy catching a cold not, and indices is significantly improved before treating; And resveratrol Spirulin composition of the present invention and preparation thereof can reduce the index of monoglyceride and the cholesterol of diabetics significantly as can be seen from the table, show that resveratrol Spirulin composition of the present invention and preparation thereof have good preventive and therapeutic action to the diabetic complication hyperlipidemia.
Test example 4 typical cases
Lu, the woman, 58 years old, hypertensive cerebral coronary heart disease, sick time 7 years was eaten many medicines, but was not felt any better, and took resveratrol spirulina tablet of the present invention, was almost recovered after 3 months, and the symptoms such as the dyspnea of the front appearance of taking medicine, fatigue also disappear.
Song, the man, 67 years old, coronary heart disease, for many years ill, take resveratrol preparation of spirulina tablet of the present invention after 3 months, be almost recovered, irregularly intermittent and regularly intermittent pulse disappears, without cardiopalmus, fatigue, nervous sensation.
Zhang, the woman, 72 years old, because hypertension got cerebral infarction and hemiplegia, can not take care of oneself, take resveratrol preparation of spirulina tablet of the present invention after 3 months, pick body, life can take care of oneself, and can carry out general productive labor.
Lee, the man, 58 years old, suffer from coronary sclerosis,, do not feel any better after 1 year through hospitalize, use resveratrol preparation of spirulina tablet of the present invention after 3 months, symptom takes a turn for the better, and symptom uncomfortable in chest, that breathe hard, feel run-down no longer occurs.
Claims (10)
1. a resveratrol Spirulin composition is characterized in that, described compositions comprises that weight portion is that spirulina and 5-30 part purity of 10-100 part is higher than high-purity resveratrol of 80%.
2. resveratrol Spirulin composition as claimed in claim 1 is characterized in that, described compositions comprises that also weight portion is the Radix Astragali extract of 1-15 part, the tartary buckwheat extract of 1-15 part and the vitamin C of 0.5-3 part.
3. the solid preparation made of resveratrol Spirulin composition as claimed in claim 2 and adjuvant is characterized in that, described solid preparation comprises tablet, capsule, granule or powder; Described adjuvant comprises one or more in diluent, disintegrating agent, binding agent or the lubricant; Described diluent is selected from one or more in lactose, sorbitol, xylitol, mannitol, pregelatinized Starch, sucrose, dextrin or the microcrystalline Cellulose; Described disintegrating agent is selected from one or more in cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, polacrilin potassium, low-substituted hydroxypropyl cellulose or the hydroxyethylmethyl-cellulose; Described binding agent is selected from one or more in methylcellulose, hydroxypropyl cellulose, hypromellose, hydroxy methocel, sodium carboxymethyl cellulose, polyvidone, polyethylene glycol 6000 or the Macrogol 4000; Described lubricant is selected from one or more in magnesium stearate, micropowder silica gel, silicon dioxide, Pulvis Talci, hydrogenated vegetable oil or the sodium laurylsulfate.
4. solid preparation as claimed in claim 3, it is characterized in that, described adjuvant comprises that also weight portion is the beta-schardinger dextrin-of 1-20 part, and described beta-schardinger dextrin-is selected from one or more in glucose group-beta-cyclodextrin, HP-β-CD or the ethyl-beta-schardinger dextrin-.
5. solid preparation as claimed in claim 4 is characterized in that, described solid preparation is tablet, and described adjuvant is hydroxy methocel, microcrystalline Cellulose, silicon dioxide and magnesium stearate, and the parts by weight of described each composition of tablet are:
6. solid preparation as claimed in claim 3, it is characterized in that, described solid preparation is capsule, and described adjuvant is mannitol, pregelatinized Starch and cross-linking sodium carboxymethyl cellulose, described mannitol and compositions form solid dispersion, and the parts by weight of described each composition of capsule are:
7. resveratrol Spirulin composition as claimed in claim 1 or 2, it is characterized in that, described high-purity resveratrol is to form take plant as feedstock purification, and described plant is selected from Semen Vitis viniferae skin slag, Semen arachidis hypogaeae, Rhizoma Polygoni Cuspidati, and described method of purification is a kind of in the following method:
Semen Vitis viniferae skin ground-slag is broken, add the 70%-90% alcohol reflux 3 times, the amount that adds ethanol for the first time is 5-10 times of Semen Vitis viniferae skin slag, backflow 3-5h, the amount that adds for the second time ethanol is 3-6 times of Semen Vitis viniferae skin slag, backflow 2-4h, the amount that adds for the third time ethanol is 1-3 times of Semen Vitis viniferae skin slag, backflow 1-3h, merge backflow, filter, it is 70 ℃ of thick pastes that relative density is 1.30-1.32 that filtrate is concentrated into temperature, the dry Semen Vitis viniferae skin slag extract that gets; Semen Vitis viniferae skin slag extract is dissolved in the sodium bicarbonate aqueous solution of 1-5%, stir 20-50min, sediment separate out washes precipitate to neutrality with water, then precipitate is added in the water that 10-15 doubly measures, in 85-90 ℃ of dissolving, aqueous solution slowly is cooled to 10-25 ℃, leaves standstill, wash out precipitation, lyophilization makes purity and is higher than 90% resveratrol;
Or with the Testa arachidis hypogaeae crushed after being dried, Testa arachidis hypogaeae after pulverizing is carried out supercritical carbon dioxide extraction, with dehydrated alcohol and propanol as entrainer, Testa arachidis hypogaeae, entrainer, the mass ratio of the circulation consumption of carbon dioxide hourly is 1:0-0.2:10-30, extractor pressure is 6-15Mpa, and temperature is 40-55 ℃, and knockout drum pressure is 3.5-6.5Mpa, temperature is 20-25 ℃, extraction time 2-3h collects extract, and is concentrated, with macroporous resin adsorption post on the concentrated solution, ethanol with 25%-30% carries out eluting, collects eluent, and concentrate drying gets purity and is higher than 90% resveratrol;
Or with the Rhizoma Polygoni Cuspidati pulverizing, with 75-95% soak with ethanol 5h, reflux, extract, twice again, and the amount that adds ethanol for the first time is 5-10 times of Rhizoma Polygoni Cuspidati, backflow 2-4h, and the amount that adds ethanol for the second time is 2-5 times of Rhizoma Polygoni Cuspidati, backflow 1-3h merges backflow, filters, and is condensed into thick paste; Be that 1:50 adds water with volume ratio by weight with thick paste, ultrasonic dissolution filters, and inclining supernatant, adds 3-5 ethyl acetate extraction doubly three times, combined ethyl acetate liquid, and regulating pH value with dilute alkaline soln is 8-9, concentrated, gets the resveratrol crude product; The resveratrol crude product is dissolved in upper macroporous resin column in the ethanol of 2 times of amounts, be eluted to eluent with distilled water first and be colourless, be 50% ethanol eluting again with concentration, collect eluent, concentrated, be the mixed liquor recrystallization of 5:2 with ethanol and ethyl acetate volume ratio, obtain purity and be higher than 90% resveratrol;
Perhaps described high-purity resveratrol is prepared from by following any chemical synthesis process:
Be raw material with 3,5-dimethoxy benzaldehyde, under the catalysis of highly basic, carry out condensation reaction with PARA METHOXY PHENYL ACETONITRILE, form 3,4 ', 5-trimethoxy stilbene nitrile, through hydrolysis, make 3,4 ' again, the acid of 5-trimethoxy stilbene, under the catalysis of Cu, carry out decarboxylic reaction and obtain trans-3,4 ', 5-trimethoxy stilbene obtains purity by demethylating reaction at last and is higher than 98% resveratrol under the catalysis of Boron tribromide;
Or with 3, the 5-3,5-dimethoxybenzoic alcohol is raw material, make 3 with the Lucas reagent reaction, 5-dimethoxy benzyl chlorine, make 3,5-dimethoxy-benzyl diethyl phosphonate with the NSC 5284 reaction again, under the catalysis of sodium alkoxide, make (E)-3 with P-methoxybenzal-dehyde again, 4 ', 5-trimethoxy stilbene is at last at AlCl
3Effect under demethylation make purity and be higher than 98% resveratrol;
Or with 4-hydroxyl phenylacetic acid and 3, the 5-4-dihydroxy benzaldehyde is raw material, make (E)-2-(4 '-hydroxy phenyl through perkin reaction)-3-(3 ', 5 '-dihydroxy phenyl)-acrylic acid, carry out again decarboxylation, isomerization reaction makes purity and is higher than 98% resveratrol.
8. resveratrol Spirulin composition as claimed in claim 2 is characterized in that, the preparation method of described Radix Astragali extract is: Radix Scutellariae is pulverized, decoct with water three times, for the first time water consumption be astragalus weight 10-15 doubly, decocted 2-3 hour, the second water consumption be astragalus weight 5-10 doubly, decocted 1-2 hour, water consumption is 2-5 times of astragalus weight for the third time, decocted 1-2 hour, collecting decoction filters, and filtrate is concentrated, drying makes Radix Astragali extract;
The preparation method of described tartary buckwheat extract is: Radix Et Rhizoma Fagopyri Tatarici is pulverized, added the 75%-80% alcohol reflux 3 times, the amount that adds ethanol for the first time is 10-15 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 2-5h, the amount that adds for the second time ethanol is 5-10 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 1-3h, and the amount that adds for the third time ethanol is 2-3 times of Radix Et Rhizoma Fagopyri Tatarici, backflow 1-3h, merge backflow, filter, filtrate is concentrated, drying makes tartary buckwheat extract.
9. the method for making of solid preparation as claimed in claim 5 is characterized in that, described method comprises the steps:
1) spirulina pulverizing, vitamin C are pulverized, with high-purity resveratrol, Radix Astragali extract and tartary buckwheat extract mix homogeneously, crossed the 40-60 mesh sieve, make the resveratrol Spirulin composition;
2) beta-schardinger dextrin-is added in the water that 2-5 doubly measures, fully be ground to water quantities and be less than 5% pastel, grind the lower described resveratrol Spirulin composition of step 1) that adds, mix homogeneously, lyophilization makes clathrate;
3) with clathrate and microcrystalline Cellulose, hydroxy methocel, mix homogeneously makes mixture, granulates, and adds silicon dioxide and magnesium stearate, mix homogeneously, tabletting again.
10. the method for making of solid preparation as claimed in claim 6 is characterized in that, described method comprises the steps:
1) gets described resveratrol Spirulin composition;
2) mannitol is placed the water-bath heating and melting, make fused mass, stir the lower resveratrol Spirulin composition that adds, mix homogeneously is crossed the 100-120 mesh sieve, makes solid dispersion;
3) with solid dispersion and pregelatinized Starch and cross-linking sodium carboxymethyl cellulose mix homogeneously, make mixture;
4) described mixture is packed in No. 0 capsule, make capsule.
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| EP2944202A1 (en) * | 2014-05-14 | 2015-11-18 | Lypo C AB | A method for manufacturing a mixture of lypo-spheric vitamin C and a mixture of lypo-spheric vitamin C |
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| CN110133078A (en) * | 2019-04-25 | 2019-08-16 | 广州万孚生物技术股份有限公司 | Glutamic-pyruvic transaminase Electrochemical Detection composition, its application, electrochemical sensor and detection method |
| WO2024040630A1 (en) * | 2022-08-23 | 2024-02-29 | 南京盛德生物科技研究院有限公司 | Composition for controlling blood glucose, preparation method therefor, and use of same in reducing gi value of foods |
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