CN1278737C - Compound medicinal formulation with bioactivity - Google Patents
Compound medicinal formulation with bioactivity Download PDFInfo
- Publication number
- CN1278737C CN1278737C CN 200310104068 CN200310104068A CN1278737C CN 1278737 C CN1278737 C CN 1278737C CN 200310104068 CN200310104068 CN 200310104068 CN 200310104068 A CN200310104068 A CN 200310104068A CN 1278737 C CN1278737 C CN 1278737C
- Authority
- CN
- China
- Prior art keywords
- oil
- blood
- compound
- radix
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The present invention provides a compound medicinal preparation with bioactivity. The present invention is characterized in that a medicinal or food acceptable preparation is prepared by appropriate medicinal or edible auxiliary materials and raw materials with the weight percent of 20% to 85% of chloris virgata swartz, 5% to 30% of radix notoginseng, 0% to 60% ofginkgo leaves, 0% to 50% of schisandra propinqua, 0% to 35% of safflower, 0% to 30% of hemlock parsley, 0% to 32% of astragalus roots, 0% to 5% of borneol, 0% to 10% of hirudin, 0% to 13% of lumbrokinase and 0% to 3% of snake venom defibrinogenase. The present invention has the good comprehensive functions of blood sugar regulation, blood fat regulation, liver protection, hemodynamics improvement, antioxidation, etc. Research proves that the present invention has a good therapeutical function to a plurality of blood circulation aplastic diseases, such as myocardial and cerebral ischemia, thrombosis, etc. The present invention has a better function to diabetes patients, especially diabetes patients with hyperlipemia and complication thereof.
Description
Technical field
The present invention relates to a kind of compound Chinese medicinal preparation, especially a kind of biologically active is used for the treatment of the compound preparation of disturbance of blood circulation disease etc.
Background technology
Blood is the metabolic carrier of human body, has the relatively stable and defense function of environment in transportation, the maintenance.Blood goes wrong, and will directly influence the performance of its function.Blood constantly circulates in the blood vessel of human body, and blood and blood vessel influence each other.Therefore, the disease of cardiovascular system, light then influence the metabolism of human body, accelerate human senility, heavy then critical illness such as myocardial infarction, apoplexy take place.Blood glucose is often mixed interpromoting relation in five elements mutually with blood fat, and the blood circulation to health causes damage jointly.Diabetes are endocrine metabolism diseases, with hyperglycemia as its common leading indicator, reduce water, the metabolic disturbance of electrolyte that causes sugar, protein, fat three big materials and secondary because of insulin sensitivity, be subjected to the influence of sugar decomposition dysbolismus in addition, often cause the under-supply of human body energy, make body have to employ fat even protein comes makeup energy, so excessive thirst, polyuria, polydipsia, polyphagia, tired, clinical symptoms such as become thin have just occurred.In addition, owing to fatty, protein decompose not exclusively, make a large amount of toxicity mesostates of generation in the body, thereby cause various acute and chronic complication as ketoboidies and so on.Therefore, diabetes are as a kind of lifelong participation disease, except metabolism disorder disease group occurring, its seriousness is that also it can cause various complication, as aorta, coronary artery, arteriae cerebri, renal artery and limbs peripheral arterial etc. are big, medium-sized artery is atherosis, diabetic nephropathy, retina, nerve, dermatosis infect etc., these complication be cause patient disability, disable, lethal principal element, its mortality rate has come after tumor and the cardiovascular diseases, occupies the 3rd.Now, blood circulation disease, endocrine disturbance's disease and hepatic disease and some complication etc. are the diseases of serious harm human health, especially these several diseases have refractory, complication characteristics how, a kind of combined therapy effect of urgent clinical needs is good, can reduce medical expense, improve the medicine of patient's life quality.
Summary of the invention
The present invention aim to provide a kind of reasonable recipe, comprehensive therapeutic effect good, quality controllable be the compound medicine of primary raw material with Radix seu Caulis Embeliae Parviflorae and Radix Notoginseng.
The present invention is directed to above-mentioned existing situation, on the basis of excavating medical treatment side among the people, find through scientific research, behind plurality of Chinese compound recipes such as Radix seu Caulis Embeliae Parviflorae and Radix Notoginseng, can work in coordination with mutually between each composition, the common blood function of regulating, treatment also improves disease or the functional disorder that causes because of blood system or cardiovascular and cerebrovascular vessel variation, endocrine disturbance etc.Thereby can solve the integrated control problem of blood circulation disease, endocrine disturbance's disease and hepatic disease and some complication etc. preferably.
Chinese medicine compound provided by the invention is equipped with an amount of medicinal or edible adjuvant by following raw materials by weight percent, makes acceptable preparation on medicine or the food:
Radix seu Caulis Embeliae Parviflorae 20%～85% Radix Notoginseng 5%～30% Folium Ginkgo 0%～60%
MANSHANXIANG 0%～50% Flos Carthami 0%～35% Rhizoma Chuanxiong 0%～30%
The Radix Astragali 0%～32% Borneolum Syntheticum 0%～5% hirudin 0%～10%
Lumbrukinase 0%～13% snake venom defibrase 0%～3%.
Described raw material is former vegetable drug or is their different extracts.Wherein:
Radix seu Caulis Embeliae Parviflorae is the whole herb with root of Primulaceae Radix seu Caulis Embeliae Parviflorae Lysimachia barystachys Bung. and short peach Lysimachia clethroides Duby, menoxenia, dysmenorrhea, metrorrhagia, cold anemopyretic, traumatic injury, edema, hypertension, the rheumatalgia etc. of being used for the treatment of among the people, it is led and contains flavone compound, and content is 0.1%～2%.The Radix seu Caulis Embeliae Parviflorae flavone has effects such as activating blood circulation to dissipate blood stasis, the interior free radical of removing blood vessel, inhibition platelet activating factor, blood fat reducing, blood sugar lowering preferably.
Radix Notoginseng (having another name called Radix Notoginseng, Radix Notoginseng, southern Radix Ginseng) is the araliaceae ginseng plant, its root, leaf, flower etc. all have medical value, mainly contain ginsenoside's (content is 2%～14%) and other material, it can effectively improve sanguimotor hemodynamics, blood viscosity lowering, blood sugar lowering, blood fat, the activity of raising SOD enzyme, the generation that prevents vascular inflammation and tonification are strong etc.
The Folium Ginkgo Semen Ginkgo leaves that is called among the people is mainly used in cardiovascular and cerebrovascular disease, and contained ginkgetin, bilobalide are its main active.
MANSHANXIANG (rattan XIANGSHU, the Caulis Kadsurae Longipedunculatae etc. of being called among the people) is used as medicine with ratan, have dredge through invigorate blood circulation, the function of promoting blood circulation and breaking stagnation, reducing swelling and alleviating pain, be used for the treatment of that the resistance of the passages through which vital energy circulates stasis of blood, bones and muscles pain, congestion are swollen and ache, menoxenia, dysmenorrhea, fracture etc.The main active of MANSHANXIANG is flavone, lignin etc.
Flos Carthami is the dried floral of feverfew Flos Carthami Carthamus tinctorius, is a kind of medicine food dual purpose plant, has the effect of " promoting blood circulation to restore menstrual flow, eliminating stasis to stop pain ".Be usually used in treating disturbance of blood circulation diseases such as multiple cardiac-cerebral ischemia, thrombosis clinically.Flos Carthami contains effective ingredient such as glycoside, carthamin, fatty acid, ketone, alcohol.
Rhizoma Chuanxiong is the dry rhizome of umbellate form section plant Rhizoma Chuanxiong [Ligusticum chuanxiong Hort.], contains effective ingredient such as ligustrazine, ferulic acid, phthalide analog compound, energy blood-activating and qi-promoting, wind-expelling pain-stopping.
The Radix Astragali is the dry root of leguminous plant Radix Astagali [Astragalus membranaceus (Fisch.) ge.var.mongholicus (Bge) Hsiao] or Radix Astragali [Astragalus membranaceus (Fisch.) Bge].Sweet, the tepor of nature and flavor is returned spleen, lung meridian.Main effect is a tonifying Qi and lifting yang, benefiting QI for strengthening the superficies, and promoting pus discharge and tissue regeneration strengthening, inducing diuresis to remove edema is one of most important medicine in the Qi-tonifying drug.Clinical each sections such as that the Radix Astragali is widely used in is inside and outside, woman, youngster, face, in the clinical practice of internal medicine, find that all kinds of cardiovascular and cerebrovascular diseases to the existing syndrome of blood stasis due to qi deficiency of multilist can obtain certain or is worth compelling curative effect at recent years.The contained main biological activity chemical constituent of the Radix Astragali is Radix Astragali saponin class, flavonoid, astragalus polysaccharides class, amino acids etc.
Borneolum Syntheticum is the processed goods of the resin of Dipterocarpaceae plant Borneolum Syntheticum [Dryobalarops aromatica Gaertn.F.], or is used as medicine for the processed goods of Camphora Lignum Pini Nodi wet goods chemical synthesis process.This product causing resuscitation with aromatic drugs, declare the interior-heat improving acuity of vision and removing nebula clearly.
Hirudin, Lumbrukinase and snake venom defibrase be respectively from Hirudo, Lumbricus and Serpentis extraction separation come out, have anti-thrombus function preferably.
Singles (folk prescription) such as above-mentioned Radix seu Caulis Embeliae Parviflorae, Radix Notoginseng are though Chinese medicine has certain curative effect to cardiovascular and cerebrovascular disease, but its comprehensive therapeutic effect has much room for improvement, traditional medicine is always paid attention to the research of compound recipe and use and obtain curative effect preferably in clinical practice, the clinical efficacy of many compound recipes be folk prescription can not than.
Product of the present invention can be made into injectable powder, infusion solution, soft capsule, drop, oral tablet, glue as required and assists pharmaceutically acceptable various preparations such as agent, granule, also can be made into health care (or functional) food such as cookies, confection, beverage, fruit jelly.
Medical accessory of the present invention is mannitol, sorbitol, lactose, sucrose, starch and derivant thereof, cellulose and derivant thereof, aminoacid and derivant thereof, NaCl, CaCl
2, CaCO
3In one or more organic or inorganic things.
Edible adjuvant of the present invention is one or more in soybean oil, Oleum Arachidis hypogaeae semen, flour, osseocolla, pectin, gelatin, xanthan gum, Folium Camelliae sinensis, the Mel.
In order to improve pharmaceutically active, to reduce drug dose, the oral formulations when not making aqueous solution during preparation can become the micropowder of particle diameter 1～200 μ m with ultra fine such as comminution by gas stream or ball mill pulverizing with raw material.
It is one or more plant edible foods or medicinal oil in refine Testa oryzae oil, safflower oil, linoleic acid, alpha-linolenic acid, gamma-Linolenic acid, polyunsaturated fatty acid, Semen Tritici aestivi germ oil, Radix Oenotherae erythrosepalae oil, perilla oil, Oleum Hippophae, Semen Lini oil, bathypelagic fish oil, eicosapentaenoic acid, docosahexenoic acid, Semen Maydis oil, Oleum Vitis viniferae, Folium et Cacumen Artemisiae Halodendri seed oil, walnut oil, soybean oil, the Oleum Arachidis hypogaeae semen that the present invention makes the used solvent substrate of compound capsules product.
It is one or more edible or pharmaceutic adjuvants in cellulose and derivant, poly-mannose and derivant thereof, Semen Plantaginis glue, xylitol, Sorbitol, lactose, mannitol, the starch that the present invention makes compound tablet and the used adjuvant of capsule product.
It is one or more pharmaceutic adjuvants in mannose, mannitol, xylitol, Sorbitol, lactose, sodium chloride, the sodium phosphate that the present invention makes the used adjuvant of compound injection product.
It is in gelatin, my white glues, alginate, protide, vegetable oil, starch and derivant thereof, carboxymethyl cellulose salt (SCMC), cellulose acetate-phthalate (CAP), ethyl cellulose (EC), methylcellulose (MC), hypromellose (HPMC), polyester, Polyethylene Glycol (PEG), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), polyamide, the polylactic acid one or more that the present invention makes the used microcapsule capsule material of compound recipe microcapsule product.
In described compound oral administration preparation product, can use one or more medicinal or food colorings in Carthamus yellow, safflower red pigment, carotene, lycopene, phylloxanthin, chlorophyll, amaranth, the brilliant black for the purpose that makes product reach human oriented design, perhaps use one or more the medicinal or flavorants in NINGMENGXIANG, Fructus Citri tangerinae perfume (or spice), vanillin, Mentholum, the muscone.
The course of processing of described compound capsules is: with compound medicine with ultra fine such as comminution by gas stream or ball mill pulverizing, reach particle diameter less than 200 μ m, in the compound medicines adding solvent substrate with super-refinement, fully stir, dissolve, filter, outgas, deliver in the jar of filling machine top, stand-by; Be ready to the gelatin solution that the rubber in the soft capsule filling machine top insulation gelatin jar is used simultaneously, stand-by; Under 10,000 grades, 21 ℃～25 ℃, the condition of RH%:39～41%, start rotating mould press pelleting, the soft capsule of making is cleaned, 28 ± 2 ℃ dry 19～27 hours down, packing, packing get product.
The course of processing of described compound recipe injectable powder is: under 10,000 grades condition, qualified medicine and adjuvant are dissolved in the water for injection together, after decolouring waits processing, add water for injection and be diluted to volume required.Filter, after the processing such as filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the following membrane filtration of 0.2 μ m.Fine straining liquid is sent into racking machine, by every 1 ~ 2ml packing, covers the lid of trough of belt, sends into frozen vacuum dryer, is chilled to 35 ℃ ~ 40 ℃ fast, 2 ~ 3 hours, progressively slowly is warming up to 35 ℃ ~ 45 ℃ (needing 10 hours approximately).The jam-pack lid takes out goods, Zha Gai, packing, check, qualified pharmaceutical acceptable powder pin finished product.
The course of processing of described compound recipe microcapsule is: any with in prior art () coacervation, (two) solvent-nonsolvent method, (three) multiple emulsion encapsulation circle, the poly-method of (four) reduction of area, (five) chemical radiation, (six) spray drying method, (seven) spray congealing, (eight) air suspension.
The course of processing of described Hausmam Amin 20 is: under the condition of 10,000 grades and nitrogen protection, the aminoacid with trace is dissolved in water for injection earlier, and notes it is dissolved fully, and is stand-by; The herbal extract of recipe quantity is added the proper amount of water for injection dissolving, and note it is dissolved fully, filter, stand-by; Again other aminoacid are dissolved in an amount of water for injection, add above-mentioned solvent aminoacids solution and medicinal liquid, add mannitol and be diluted to volume requiredly with water for injection, add antioxidant, regulate to wait and oozes, add water for injection to finally volume required.Filter, after the processing such as filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the following membrane filtration of 0.2 μ m.Fine straining liquid is sent into racking machine, by every bottle of required 250ml packing, covers the butyl rubber lid, and the preparation preheating is 121 ℃ of sterilizations (15 minutes).Or, cool off gradually towards hot water with the sterilization of rotation steriliser.Shady and cool place preserves.Packing, check, the qualified finished product that gets.
The extraction separation of two kinds of special medical material effective ingredient:
1, the extraction of Radix seu Caulis Embeliae Parviflorae effective ingredient
1 kilogram of Radix seu Caulis Embeliae Parviflorae, beat coarse powder and cross 10～20 orders, with 10 kilogram of 80% soak with ethanol 48 hours, filter, use 8 kilogram of 80% soak with ethanol 24 hours twice more respectively, merge soak, filter, activated carbon decolorizing with 0.4% filters, and filtrate further is concentrated into 1/3 volume, cold preservation is placed more than the 12h, filter, filtrate adds long-pending 0.5～2% active carbon of solution body and boils decolouring in 5 minutes, filtered while hot, filtrate through the membrane filtration of 0.4 μ m once, concentrate recovery ethanol to there not being the alcohol flavor, spray drying gets Radix Angelicae Sinensis Resina garciniae ketone content at the Radix seu Caulis Embeliae Parviflorae effective component extracts more than～35%.This product can be used as in a plurality of prescriptions among the present invention and uses.
If will do injection or make product exquisite more, this effective site further can be refined to the Radix seu Caulis Embeliae Parviflorae general flavone content and reach 62%～89%.Process for purification can be selected the conventional separation method of flavone such as resin method, silica gel column chromatography for use.
2, the extraction of MANSHANXIANG effective ingredient
1 kilogram of MANSHANXIANG, beat coarse powder and cross 10～20 orders, with 8 kilogram of 60～80% alcohol heat reflux 4 hours, filter, used 6 kilogram of 60～80% alcohol heat reflux more respectively 2 hours twice, merge extractive liquid,, filter, activated carbon decolorizing with 0.4% filters, and filtrate further is concentrated into 1/3 volume, cold preservation is placed more than the 12h, filter, filtrate adds long-pending 0.5～2% active carbon of solution body and boils decolouring in 5 minutes, filtered while hot, filtrate through the membrane filtration of 0.4 μ m once, concentrate recovery ethanol to there not being the alcohol flavor, spray drying gets MANSHANXIANG extract (flavones content is more than～31%).This product can be used as in a plurality of prescriptions among the present invention and uses.
If will do injection or make product exquisite more, this effective site further can be refined to the MANSHANXIANG general flavone content and reach 62%～89%.Process for purification can be selected the conventional separation method of flavone such as resin method, silica gel column chromatography for use.
The present invention compared with prior art has following advantage and effect: this compound preparation has preferably blood sugar regulation, blood lipid regulation, protects the liver, improves comprehensive functions such as hemodynamics, antioxidation, studies confirm that it has therapeutical effect preferably to disturbance of blood circulation diseases such as multiple cardiac-cerebral ischemia, thrombosiss.To the diabetes patient, especially will have better effect to diabetes patient and the complication thereof that is mixed with hyperlipemia.
The specific embodiment
Embodiment 1
Compound Chinese angelica-root rattan granule, prescription:
Radix seu Caulis Embeliae Parviflorae 200g Radix Notoginseng 50g Folium Ginkgo 70g
MANSHANXIANG 30g Flos Carthami 12g Rhizoma Chuanxiong 10g
Radix Astragali 10g Borneolum Syntheticum 2g hirudin 3g
Lumbrukinase 3.5.g sucrose 3000g dextrin 400g
Snake venom defibrase 1g ethanol is an amount of.
Preparation method: by the prescription material of getting it filled, beat coarse powder and cross 10～20 orders, measured 65% soak with ethanol 48 hours with 10 times, filter, measured 70% alcohol heat reflux 2 hours twice, merge extractive liquid, with 8 times respectively again, filter, activated carbon decolorizing with 0.3% filters, and filtrate further is concentrated into 1/3 volume, cold preservation is placed more than the 24h, filter, filtrate adds long-pending 0.5～2% active carbon of solution body and boils decolouring in 5 minutes, filtered while hot, filtrate through the membrane filtration of 0.4 μ m once, concentrate recovery ethanol to there not being the alcohol flavor, spray drying gets medicinal substances extract.Add Borneolum Syntheticum, hirudin, Lumbrukinase, snake venom defibrase and adjuvant, granulate, be distributed into 1000 bags by common granulation.Each edible one bag, every day 1～2 time.
Embodiment 2
Compound Chinese angelica-root rattan drop pill, prescription:
Radix seu Caulis Embeliae Parviflorae extract (containing total flavones＞50%) 35g
Radix Notoginseng total arasaponins (＞88%) 25g:
Carthamin 15g
PEG400 200g
By common drop pill preparation method preparation, the tolerant heavy about 275mg of every intragranular can get 1000.
Embodiment 3
Compound Chinese angelica-root rattan freeze-dried powder, prescription:
Radix seu Caulis Embeliae Parviflorae extract (containing total flavones＞75%) 24g
Radix Notoginseng total arasaponins (＞95%) 25g
Rhizoma Chuanxiong extract (containing ligustrazine＞67%) 12g
Mannitol 100g
Be prepared into lyophilized formulations by common lyophilization, can make the compound Chinese angelica-root rattan freeze-dried powder of the specification of 1000 49mg.
Embodiment 4
Compound Chinese angelica-root rattan oral liquid, prescription:
Radix seu Caulis Embeliae Parviflorae 320g
Radix Notoginseng 66g
Mel 1000g
Distilled water adds to 10kg
Preparation method: get the recipe quantity medical material, beat coarse powder and cross 10～20 orders, with 10 times of amount 65% soak with ethanol 48 hours, filter, measure 70% alcohol heat reflux 2 hours twice with 8 times respectively again, merge extractive liquid,, filter, the activated carbon decolorizing with 0.3% filters, filtrate further is concentrated into 1/3 volume, cold preservation is placed more than the 24h, filters, and filtrate adds long-pending 0.5～2% active carbon of solution body and boils decolouring in 5 minutes, filtered while hot, filtrate through the membrane filtration of 0.4 μ m once concentrates and reclaims ethanol to there not being the alcohol flavor, adds adjuvant, by common oral liquor preparation, can get 1000 oral liquid.
Embodiment 5
The transfusion of compound Chinese angelica-root rattan eight seed amino acids, prescription (1000ml):
Radix seu Caulis Embeliae Parviflorae extract (containing total flavones＞85%) 0.2g Radix Notoginseng total arasaponins (＞95%) 2g
L-isoleucine 3.82g L-leucine 5.03g
L-lysine acetate 4.52g L-methionine 2.34g
L-phenylalanine 5.65g L-threonine 2.78g
L-tryptophan 1.0g L-valine 3.98g
Mannitol 70g
Preparation technology: under the condition of 10,000 grades and nitrogen protection, the L-tryptophan with trace is dissolved in water for injection～20ml earlier, and notes it is dissolved fully, and is stand-by; The Radix seu Caulis Embeliae Parviflorae extract of recipe quantity and the water for injection of Radix Notoginseng total arasaponins adding～200ml are dissolved, and note it is dissolved fully, filter, stand-by; Again other aminoacid are dissolved in an amount of water for injection～400ml, add above-mentioned solvent tryptophan liquid and astragalus liquid, add mannitol and be diluted to volume required～800ml, add antioxidant with water for injection, regulate to wait and ooze, add water for injection to finally volume required.Filter, after the processing such as filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the following membrane filtration of 0.2 μ m.Fine straining liquid is sent into racking machine, by every bottle of required 250ml packing, covers the butyl rubber lid, and the preparation preheating is 121 ℃ of sterilizations (15 minutes).Or, cool off gradually towards hot water with the sterilization of rotation steriliser.Shady and cool place preserves.Packing, check, the qualified finished product that gets.Can make the compound Chinese angelica-root rattan eight seed amino acids transfusion finished product of 4 bottles of 250ml specifications.
Embodiment 6
Compound Chinese angelica-root rattan soft capsule, prescription (1000):
Radix seu Caulis Embeliae Parviflorae extract (containing total flavones＞35%) 35g Radix Notoginseng total arasaponins (＞88%) 65g
Borneolum Syntheticum 28g ethyl hydroxybenzoate 2g
Vanillin 1g safflower oil 300g
Implement promptly to get 1000 by technical scheme, promptly get every soft capsule finished product that contains medicine 128mg with fragrance.
Embodiment 7
Single coacervation prepares compound Chinese angelica-root rattan microcapsule, prescription:
Radix seu Caulis Embeliae Parviflorae extract 50g Radix Notoginseng total arasaponins 00g
MANSHANXIANG extract 29g gelatin 2000g
Preparation technology: under 100,000 grades condition, with the gelatin solution of gelatin melt into 60000ml, add Radix seu Caulis Embeliae Parviflorae extract, Radix Notoginseng total arasaponins and MANSHANXIANG extract, stir, acetic acid with 10% is transferred pH3.5 ~ 3.8, and reactor was placed 50 ℃ of water-bath insulated and stirred 45 minutes.Drip metabisulfite solution (diluent), examine under a microscope till the poly-encystation, pour into immediately in the diluent that is stirring, treat the gelling sedimentation after, the supernatant that inclines with diluent washing 2 ~ 3 times, is removed uncongealed capsule material.Microcapsule is suspended in an amount of diluent at last again, adds 37% formalin, 2000 ~ 3000ml, stir, dropping sodium is regulated pH to 8 ~ 9, and low temperature is placed and spent the night, and filters, and is washed with water to formaldehydeless flavor, and cold drying promptly.
Embodiment 8
Spray drying method for preparation compound Chinese angelica-root rattan microcapsule, prescription:
Radix seu Caulis Embeliae Parviflorae extract 36g Radix Notoginseng total arasaponins 78g
Radix Astragali saponin 18g Borneolum Syntheticum 8g
Ethyl cellulose 4000g hypromellose 500g
Preparation technology: under 100,000 grades condition, medicine is dissolved in the aqueous isopropanol of the ethyl cellulose of 60000ml and hypromellose, selects inlet temperature at 80 ℃ ~ 100 ℃, outlet temperature is at 50 ℃ ~ 75 ℃.The spray-dried microcapsule that promptly gets.This microcapsule can directly be pressed into tablet.
Above embodiment is only for the present invention is described further, and scope of the present invention is not subjected to the limitation of illustrated embodiment.
Through experimental study, the present invention's medicine has following effect:
One, function of promoting blood circulation to disperse blood clots
1 experiment material
1.1 medicine and reagent
Adopt compound dripping pill, Herba Erigerontis tablet, FUFANG DANSHEN PIAN, the aspirin enteric coatel tablets of embodiment 2.1.2 laboratory animal
Male SD rat, Kunming mouse, male and female half and half.
2 methods and result
2.1 influence to rat blood viscosity
60 of male SD rats, body weight 320～360g is divided into 5 groups at random, 12 every group.The normal control group gives 0.5%CMC-Na10ml/kg, and positive control gives Herba Erigerontis tablet 40mg/kg, and compound recipe gives 0.1,0.2 respectively, 0.4g/kg.Each treated animal according to dosage every day gastric infusion once, continuous 6 days, the administration volume was 10ml/kg.1h after the last administration, lumbar injection 40mg/kg pentobarbital sodium anesthetized animal, carotid artery is got blood, uses the 2.7%EDTA anticoagulant, and whole blood is 9: 1 with the ratio of anticoagulant volume.Partly anticoagulation is used to measure whole blood viscosity, partly measures plasma viscosity with the centrifugal back of 2000rpm separated plasma.
Experimental result shows: rat gives compound recipe 0.1,0.2,0.4g/kg, can significantly reduce 200-30S
-1Whole blood viscosity under the shear rate and whole blood reduced viscosity, and can obviously shorten erythrocyte electrophoretic time, but packed cell volume and plasma viscosity are not had obvious influence, its action intensity has dose dependent.
2.2 influence to rat blood clotting and platelet aggregation
75 of male SD rats, 295～360g is divided into 5 groups at random, 15 every group.Dosage grouping and medication are the same.1h after the last administration, after the lumbar injection pentobarbital sodium 40mg/kg anesthesia, the carotid artery intubate is got blood, and with 3.8% sodium citrate anticoagulant, whole blood is 9: 1 with the ratio of anticoagulant volume.The centrifugal 5min of 1000rpm prepares platelet rich plasma (PRP), and the centrifugal 10min of 3500rpm prepares platelet poor plasma (PPP).By the inductive platelet aggregation rate of turbidimetry for Determination ADP-2Na, the final concentration of ADP is 6mol/l; Measure TT, PT, APTT and FIB respectively by kit method.
Experimental result shows: compound recipe can obviously prolong TT and APTT time, and effect is dose-dependence; To by the inductive platelet aggregation of ADP, high dose group has obvious inhibitory action, and middle low dose group only has effect trend.
2.3 influence to the mouse experiment microcirculation disturbance
Get 60 of 18.5～24.5g mices, male and female half and half are divided into 6 groups at random by sex and body weight, 10 every group.Laboratory temperature remains on 25 ± 1 ℃.Each treated animal every day according to dosage gastric infusion once, for three days on end.After the last administration 30 minutes, with 10% urethane 0.15ml/10g body weight intraperitoneal injection of anesthesia animal, fixing auricle, place under the micro-circulation scanning tunnelling microscope that amplifies 240 times, (artery and vein is parallel with suitable blood capillary, be third level branch) be the object of observation, dosage by 0.1mg/kg causes experimental microcirculation disturbance to mouse peritoneal injection adrenalin hydrochloride, before gathering moulding respectively, the image of 5,10,15 and 20 timesharing after the moulding, measure following four indexs: 1. (fluidised form is divided 5 grades: stagnation is 0 minute to the blood fluidised form; Grain stream is 1 minute; The grain linear flow is 2 minutes; Line grain stream is 3 minutes; Linear flow is 4 minutes); 2. arteriole caliber (A
3); 3. venule caliber (V
3); 4. capillary network is counted.Observe and write down the situation of change of every index, organize a u-test with the changing value before and after each group administration.
Experimental result shows, the compound Chinese angelica-root rattan can obviously increase arteriole and the venule caliber of experimental microcirculation disturbance mice due to the adrenalin hydrochloride, shows that it has the effect of obvious microcirculation improvement.
2.4 influence to the formation of mice thrombus in vivo
70 of 20～22g Kunming mouses, male and female half and half are divided into 7 groups at random by sex and body weight: compound recipe 0.1,0.2,0.4g/kg three dosage groups; Positive control aspirin 100mg/kg group; Herba Erigerontis tablet 60mg/kg group; Compound Salviae Miltiorrhizae 1.0g/kg group; The blank group; Every group 10.Each is organized all by 20ml/kg volume gastric infusion, once a day, and continuous 8 days.Irritated in 5th behind the stomach 30 minutes, each organizes the equal back of mice subcutaneous injection 1% carrageenin 40mg/kg, behind the 72h, observes afterbody thrombosis, measure afterbody total length and thrombosis length, calculate the percent of thrombosis length with afterbody thrombosis length divided by length overall.The results are shown in Table 1.
Table 1
| Group | Dosage (g/kg) | Number of animals (only) | Thrombosis length percent (X ± SD%) |
| 0.5％CMC-Na | 20ml | 10 | 37.34±24.18 |
| Aspirin | 100mg | 10 | 2.56±4.14 ** |
| Herba Erigerontis tablet | 60mg | 10 | 5.51±6.46 ** |
| FUFANG DANSHEN PIAN | 1.0g | 10 | 6.58±9.99 |
| The compound Chinese angelica-root rattan | 0.1g | 10 | 10.10±6.34 ** |
| 0.2g | 10 | 5.04±7.45 ** | |
| 0.4g | 10 | 2.52±4.59 ** |
Compare with the blank group: * P＜0.05, * * P＜0.01
Experimental result shows: the mouse tail thrombosis that compound Chinese angelica-root rattan and each positive controls on Carrageenan are brought out has remarkable inhibitory action.And the compound Chinese angelica-root rattan of embodiment has good dose-effect relationship.
Two, hypoglycemic activity
1 experiment material
1.1 medicine and reagent
Adopt the granule of embodiment 1, during test, it is made into 0.06g/ml, 0.03g/ml, 0.015g/ml and 0.0075g/ml concentration with 0.5%CMC-Na, for preventing to separate out, now with the current.Diabetes pill, adrenalin hydrochloride injection, glucose, the commercial product of alloxan.Blood glucose, T-CHOL and triglyceride are measured test kit, and the saccharifying serum albumin is measured test kit.
1.2 animal
Laboratory animal adopts the regular grade Kunming mouse.
2 methods and result
2.1 influence to normal mouse blood sugar
Select 50 of 18～20g mices, male and female half and half are divided into 5 groups at random by sex and body weight: matched group; Diabetes pill 2.5g/kg group; 4 group 0.3 of embodiment, 0.6,1.2g/kg three dosage groups.Each is organized mice and according to dosage distinguishes gastric infusion 1 time on an empty stomach morning every day, and matched group gives 0.5%CMC-Na20ml/kg, continuous 7 days.Fasting is 12 hours after the last administration, in morning on the 8th the eye socket vein get blood, separation of serum is used glucose oxidase method
[1]Measure fasting blood sugar, the significance of t check comparable group differences.The results are shown in Table 2.
Table 2
| Group | Dosage (g/kg) | Number of animals (only) | Blood sugar concentration (X ± SD, mmolL -1) |
| 0.5％CMC-Na | 20ml | 10 | 8.45±1.58 |
| Diabetes pill | 2.5g | 10 | 6.34±1.12 * |
| The compound Chinese angelica-root rattan | 0.3g | 10 | 8.44±1.14 |
| 0.6g | 10 | 8.42±1.63 | |
| 1.2g | 10 | 7.58±1.71 |
Compare with matched group,
*P＜0.01
Experimental result shows that three dosage of compound Chinese angelica-root rattan gavage 7 days continuously, and normal mouse blood sugar level is not had obvious influence.
2.2 influence to mice glucose hyperglycemia
Select 77 of 20～22g mices, the male and female dual-purpose is divided into 7 groups at random by sex and body weight, 11 every group: blank group, model group, diabetes pill group and embodiment 4 dosage groups.Each treated animal in morning every day on an empty stomach gastric infusion once, matched group gives 0.5%CMC-Na20ml/kg, continuous 8 days.Fasting is 12 hours before the last administration, and behind the last 30 minutes, except that blank group intraperitoneal injection of saline 20ml/kg, all the other respectively organized equal lumbar injection 12.5% glucose solution 20ml/kg, measuring blood sugar of blood extracting concentration behind the 30min.The results are shown in Table 3.
Table 3
| Group | Dosage (g/kg) | Number of animals (only) | Blood sugar concentration (X ± SD, mmolL -1) |
| 0.5％CMC-Na | 20ml | 12 | 9.87±2.17 * |
| Model | 20ml | 12 | 30.19±6.88 |
| Diabetes pill | 2.5g | 12 | 18.56±8.02 * |
| The compound Chinese angelica-root rattan | 0.15g | 12 | 24.51±12.03 |
| 0.3g | 12 | 21.99±6.03 * | |
| 0.6g | 12 | 19.98±4.9 * | |
| 1.2g | 12 | 18.96±3.75 * |
Compare with model group,
*P＜0.01
0.3,0.6,1.2g/kg continuous oral 8 days experimental result shows, the compound Chinese angelica-root rattan:, glucose induced mice blood sugar increasing is had remarkable reduction effect; 0.15g/kg effect trend is only arranged.
2.3 influence to mice adrenal gland disposition hyperglycemia
Select 84 of 20～22g mices, male and female half and half are divided into 7 groups at random by sex and body weight, 12 every group.Dosage grouping and medication are the same.Fasting is 12 hours before the last administration.After the last administration 30 minutes, except that blank group intraperitoneal injection of saline 20ml/kg, all the other respectively organized equal lumbar injection adrenalin hydrochloride 0.2mg/kg.Get blood after 30 minutes, separation of serum is measured blood glucose value.The results are shown in Table 4.
Table 4
| Group | Dosage (g/kg) | Number of animals (only) | Blood sugar concentration (X ± SD, mmolL -1) |
| 0.5％CMC-Na | 20ml | 12 | 5.57±1.47 ** |
| Model | 20ml | 12 | 12.01±1.80 |
| Diabetes pill | 2.5g | 12 | 9.56±2.29 ** |
| The compound Chinese angelica-root rattan | 0.15g | 12 | 9.84±1.75 ** |
| 0.3g | 12 | 9.37±2.37 ** | |
| 0.6g | 12 | 9.55±2.71 * | |
| 1.2g | 12 | 10.45±2.25 |
Compare with model group:
*P＜0.01;
*P＜0.05
0.15,0.3,0.6g/kg continuous oral 8 days experimental result shows, the compound Chinese angelica-root rattan:, can obviously resist mice adrenal gland disposition hyperglycemia, but heavy dose of group has only blood sugar lowering trend and no difference of science of statistics.
2.4 influence to alloxan diabetes mouse blood sugar, blood fat and saccharifying serum albumin
Get 84 of 22～24g mices, male and female half and half are divided into 6 groups at random by sex and body weight, 14 every group: blank, model, diabetes pill and 1 three dosage groups of embodiment.After water 24h is can't help in each treated animal fasting, gastric infusion according to dosage respectively, after 30 minutes, except that normal control group intraperitoneal injection of saline 20ml/kg, all the other each groups are all with the normal saline solution of the dosage lumbar injection alloxan of 200mg/kg.Irritate stomach on an empty stomach once morning every day after the moulding, continuous 21 days.Fasting 12h before the last administration, 30 minutes eye socket veins are got blood after the administration, and separation of serum is pressed kit method and is measured blood glucose, T-CHOL, triglyceride and saccharifying serum albumin concentration.
Experimental result shows: embodiment 1 each dosage group all has in various degree reduction effect to alloxan diabetes mouse model blood glucose, triglyceride and saccharifying serum albumin, but serum total cholesterol is not had obvious influence.
Three, the pharmacodynamics test of compound Chinese angelica-root rattan freeze-dried powder
With equal-volume NS and FUFANG DANSHEN ZHUSHEYE and compound Chinese angelica-root rattan freeze-dried powder respectively as feminine gender and positive control, the dirty coronary flow minimizing of guinea-pig heart (p＜0.01) is dose-effect relationship due to the compound Chinese angelica-root rattan freeze-dried powder antagonism pituitrin, is better than the compound Salviae Miltiorrhizae group.On anesthetized rat ligation ramus descendens anterior arteriae coronariae sinistrae myocardial infarction and ischemia model, compound Chinese angelica-root rattan freeze-dried powder 20,40mg/kg obviously dwindle infarction size than the NS matched group, alleviate the sum of ischemia ST section and raise and reduce serum CPK and the LDH aspect is better than the compound Salviae Miltiorrhizae group.Pallasiomy cerebral ischemia reperfusion damage model, compound Chinese angelica-root rattan freeze-dried powder 20,40mg/kg and FUFANG DANSHEN ZHUSHEYE 2000mg/kg all show reduction ischemia cerebral edema and calcium content.
Four, result on trial
1,, observes contrast before and after treating to 20 routine patients with coronary heart disease random packet.Control experiment between group, the result shows that to take the sample treatment coronary heart disease effect that embodiment 6 makes remarkable, total effective rate reaches 88.4%, compares with the matched group FUFANG DANSHEN JIAONANG, has significant difference.In addition, this product can also reduce serum total cholesterol, triglyceride, reduces blood viscosity, microcirculation improvement.It is better to take back patient's mental status.
2,32 examples suffer from the patient of hepatitis, with the oral liquid that embodiment 4 makes, every day 3 times, each 1, orally use 30 days after, patient's subjective symptoms improves significantly, and shows that through the hospital inspection result of laboratory test patient's hemogram, liver function all have good transformation.
3, compound Chinese angelica-root rattan drop pill is treated 35 routine infractions with this product, and after treatment in 14～28 days, the patient more than 95% has obtained alleviation in various degree, and wherein produce effects 41.2%, improves 54.8%.To Electrocardiographic total effective rate is 66.4%.
Five, product study of pharmacy
1, the stability of product
The lucifuge keeping at room temperature of eight samples of embodiment was placed 1,2,3,6,12 month, checked that on time outward appearance is constant substantially, and effective ingredient does not change through check yet.Therefore, think that tentatively product that various prescriptions make all can reach the shelf-life about 1 year.
2, the irritation test of injectable powder and infusion solution
Get 4 of healthy rabbits, W:2.0～2.2kg, male and female half and half, be divided into two groups, inject Radix Astragali transfusion 1ml respectively on its left and right sides lower limb quadriceps femoris, 48h puts to death rabbit behind the medicine, cut open the inspection quadriceps femoris, vertically cut and observe injection site muscular irritation reaction, and converse corresponding order of reaction by table 5.
The local muscular irritation order of reaction of table 5
| Order of reaction | Irritant reaction |
| 0 1 2 3 4 5 | No significant change mild hyperaemia, its scope is less than the hyperemia of 0.51.0cm moderate, its scope is less than the hyperemia of 0.51.0cm severe, necrosis occurs with myodegeneration, have the brown degeneration popularity necrosis to occur |
The result:
The zest of injectable powder and transfusion is 0 grade, shows the injection nonirritant.
Claims (6)
1, a kind of compound medicinal formulation of biologically active is characterized in that being equipped with an amount of pharmaceutic adjuvant by following raw materials by weight percent, makes acceptable preparation:
Radix seu Caulis Embeliae Parviflorae 20%～85%
Radix Notoginseng 5%～30%
Folium Ginkgo 0%～60%
MANSHANXIANG 0%～50%
Flos Carthami 0%～35%
Rhizoma Chuanxiong 0%～30%
The Radix Astragali 0%～32%
Borneolum Syntheticum 0%～5%
Hirudin 0%～10%
Lumbrukinase 0%～13%
Snake venom defibrase 0%～3%.
2, compound medicinal formulation according to claim 1 is characterized in that described pharmaceutic adjuvant is mannitol, sorbitol, lactose, sucrose, starch and derivant thereof, cellulose and derivant thereof, aminoacid and derivant thereof, NaCl, CaCl
2, CaCO
3In one or more organic or inorganic things.
3, compound medicinal formulation according to claim 1 is characterized in that described preparation is that tablet, the glue of injectable powder, infusion solution, drop, oral agents is assisted agent, granule.
4, compound medicinal formulation according to claim 3, the solvent substrate that it is characterized in that described capsule are one or more in refine Testa oryzae oil, safflower oil, linoleic acid, alpha-linolenic acid, gamma-Linolenic acid, polyunsaturated fatty acid, Semen Tritici aestivi germ oil, Radix Oenotherae erythrosepalae oil, perilla oil, Oleum Hippophae, Semen Lini oil, bathypelagic fish oil, eicosapentaenoic acid, docosahexenoic acid, Semen Maydis oil, Oleum Vitis viniferae, Folium et Cacumen Artemisiae Halodendri seed oil, walnut oil, soybean oil, the Oleum Arachidis hypogaeae semen.
5, compound medicinal formulation according to claim 3 is characterized in that the used adjuvant of described tablet and capsule is one or more in cellulose and derivant thereof, poly-mannose and derivant thereof, Semen Plantaginis glue, xylitol, Sorbitol, lactose, mannitol, the starch.
6, compound medicinal formulation according to claim 3, it is characterized in that adding in the described oral agents one or more pigments in Carthamus yellow, safflower red pigment, carotene, lycopene, phylloxanthin, chlorophyll, amaranth, the brilliant black, perhaps add one or more flavorants in NINGMENGXIANG, Fructus Citri tangerinae perfume (or spice), vanillin, Mentholum, the muscone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310104068 CN1278737C (en) | 2003-12-17 | 2003-12-17 | Compound medicinal formulation with bioactivity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310104068 CN1278737C (en) | 2003-12-17 | 2003-12-17 | Compound medicinal formulation with bioactivity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1628845A CN1628845A (en) | 2005-06-22 |
| CN1278737C true CN1278737C (en) | 2006-10-11 |
Family
ID=34842939
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200310104068 Expired - Fee Related CN1278737C (en) | 2003-12-17 | 2003-12-17 | Compound medicinal formulation with bioactivity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1278737C (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100948332B1 (en) * | 2008-01-18 | 2010-03-17 | 양지화학 주식회사 | Composition Comprising the Extracts of Lysimachia clethroides for Prevention and Treatment of Cardiovascular Diseases |
| US7906159B2 (en) | 2008-04-17 | 2011-03-15 | Vivien Chou | Herbal compositions and methods for enhancing vital energy and athletic performance |
| CN102038940A (en) * | 2009-10-09 | 2011-05-04 | 伍丽娟 | Hirudin combination medicament for treating cardiovascular and cerebrovascular diseases |
| CN101810768B (en) * | 2010-03-10 | 2012-12-05 | 滕树财 | Antithrombotic Chinese medicinal powder and preparation method thereof |
| CN102757879A (en) * | 2011-04-29 | 2012-10-31 | 袁勤生 | SOD (superoxide dismutase) white spirit and preparation process thereof |
| CN102716471A (en) * | 2012-07-03 | 2012-10-10 | 童长虹 | Anti-hyperlipidemia health-care product |
| CN103623422A (en) * | 2012-08-21 | 2014-03-12 | 余尚学 | Novel oily liquid accessory of the blood sugar-reduction soft capsule |
| CN102813914B (en) * | 2012-09-12 | 2014-11-12 | 贵州神奇集团控股有限公司 | Medicinal composition used for treating or preventing cerebrovascular disease and related diseases |
| CN104721264A (en) * | 2013-12-23 | 2015-06-24 | 无锡伟康生物科技有限公司 | Soft capsule with auxiliary effect of reducing blood sugar |
| CN103720765B (en) * | 2014-01-16 | 2017-01-11 | 珠海海滨医药生物科技有限公司 | Traditional Chinese medicine composition for treating diabetes and preparation method thereof |
| CN104857506A (en) * | 2015-05-15 | 2015-08-26 | 张家港市五湖新材料技术开发有限公司 | Traditional Chinese medicine for reducing blood fat and preparation method |
| CN106866596B (en) * | 2015-12-11 | 2019-05-17 | 浙江永宁药业股份有限公司 | A kind of Melanin inhibitor |
| CN105664146A (en) * | 2016-01-16 | 2016-06-15 | 杜志政 | Medicament for enhancing immunity and preparation method thereof |
-
2003
- 2003-12-17 CN CN 200310104068 patent/CN1278737C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1628845A (en) | 2005-06-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8859006B2 (en) | Semen cassiae soft capsule for reducing fat and losing weight and preparation method thereof | |
| CN1278737C (en) | Compound medicinal formulation with bioactivity | |
| CN1245187C (en) | Medicine for treating eye disease caused by visceral disease | |
| CN102271698A (en) | Pharmaceutical composition and use for preparing medicament thereof | |
| CN1226940C (en) | Royal jelly composition with improved sleep function | |
| CN1775261A (en) | Mingmu-Dihuang preparation and new preparing method | |
| CN1478508A (en) | Chinese medicinal composition for treating fatty liver and its preparation method | |
| CN1304769A (en) | Blood-cleaning pill | |
| CN1836680A (en) | Compound notoginsen triterpenes puerarin preparation | |
| CN1087627C (en) | Medicament for treating diabetes and its preparation method | |
| CN1748741A (en) | Little leaf deervetch herb acne removing preparation and new preparing method | |
| CN1045892C (en) | Chinese medicine Guanxintong for preventing and curing coronary heart disease and angina pectoris, and producing process thereof | |
| CN1689637A (en) | Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process | |
| CN1872327A (en) | Composition of medicine for treating diarrhea | |
| CN104524359B (en) | A kind of Chinese medicine composition, its preparation method and application | |
| CN1308002C (en) | Compound preparation of notoginseng total saponin and quzaqi aglycone and its preparing method | |
| WO2022171096A1 (en) | Use of traditional chinese medicine composition in preparation of drugs for preventing or treating diabetes and/or diabetic complications | |
| CN1557403A (en) | Medicine for treating angiocardiopathy and cerebrovascular disease and its preparing method | |
| CN107596013A (en) | A kind of extracting method of maca and its male health-care product of preparation | |
| CN106173820A (en) | A kind of nutrient formulation nano-particle preventing and treating hypertensive heart disease and preparation processing method | |
| CN104306553B (en) | A kind of food of reducing blood lipid, health care product or pharmaceutical composition | |
| CN1762417A (en) | Compound formulation of astragalus root for treating cardiovascular and cerebrovascular diseases, its preparation process and use | |
| CN1593574A (en) | Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process | |
| CN1278725C (en) | Infusion containing gen-seng, lilyturf root, Chinese magnoliavine fruit and amino acid and its production method | |
| CN112843209A (en) | Traditional Chinese medicine composition for treating chronic dizziness and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Effective date of registration: 20080902 Pledge (preservation): Pledge |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20061011 Termination date: 20100118 |