CN1698680A - Drug giving system for improving resina draconis dissolution - Google Patents
Drug giving system for improving resina draconis dissolution Download PDFInfo
- Publication number
- CN1698680A CN1698680A CN 200410027277 CN200410027277A CN1698680A CN 1698680 A CN1698680 A CN 1698680A CN 200410027277 CN200410027277 CN 200410027277 CN 200410027277 A CN200410027277 A CN 200410027277A CN 1698680 A CN1698680 A CN 1698680A
- Authority
- CN
- China
- Prior art keywords
- sanguis draxonis
- dracaena
- macrogol
- carrier
- sanguis
- 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.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a drug administering system for improving resina draconis dissolution, wherein the solid administration system has the advantages of improved dissolving degree, lowered dosage, quick action and higher bioavailability.
Description
Technical field the present invention relates to improve the preparation of Sanguis Draxonis method of dissolution and preparation in the solid preparation, utilizes the present invention to make to comprise the low dosage formulation of Sanguis Draxonis to be used for the treatment of cardiovascular and cerebrovascular disease, blood sugar lowering, anti-inflammatory analgesic, antifungal and hemostasis.Described low dosage formulation treatment cardiovascular and cerebrovascular disease, blood sugar lowering, anti-inflammatory analgesic, antifungal and hemostatic curative effect are rapider than the general solid preparation drug effect that comprises the high dose Sanguis Draxonis, the bioavailability height.
If background of invention solid chemicals Chinese medicine is difficult for discharging from preparation, or the dissolution velocity of medicine is very slow, then the bioavailability of this preparation just may have problems.Solid preparation is with after waterborne liquid contacts, and at first disintegrate becomes fine particle, is scattered in the liquid, is dissolved in then in the liquid, is absorbed by body at last.Have only the medicine of dissolved state to be absorbed by body.Medicine dissolution absorbs more rapidly, and this point is very important to insoluble medicine, and generally speaking, the rate-limiting step that insoluble medicine absorbs mainly is a rate of dissolution.Some insoluble medicine is difficult to be dissolved out from preparation, and the result can only absorb the sub-fraction of whole dosage.Usually be subjected to the medicine of dissolution rate restriction, dissolution rate improves along with the increase of dispersion.When medicine is scattered in the solid carrier, because carrier molecule has surrounded the medicine of high degree of dispersion, therefore make drug molecule be difficult for forming aggregation, drug particle diminishes, and specific surface area increases, and accelerates dissolution rate, improves bioavailability.If medicine is formed the molecular dispersion system, and carrier is a water-soluble material, then can improve the solubility property of medicine, accelerate dissolution rate.This molecular dispersion system has developed into now that preparation is efficient, the new method of quick-effective preparation.
Sanguis Draxonis is traditional rare Chinese medicine, has effects such as blood circulation promoting and blood stasis dispelling, putrefaction-removing granulation-promoting, anti-inflammatory analgesic, arresting bleeding and healing up ulcer, hard masses softening and resolving.The use of Sanguis Draxonis on China's traditional medicine has history in 1500 at least, and the xylem that Sanguis Draxonis is mainly derived from following section platymiscium is through pulverizing, with organic solvent extraction, concentrate refining and get; Or get excretory red natural resin between its cerise fruit scale, through friction processing, softening back adds adjuvants such as conch meal, Colophonium, makes it solidification forming and gets; Or adopt incised wound tree stem to flow out resin, make through processing again.The Sanguis Draxonis that Sanguis Draxonis that above-mentioned different material source produces or different processing methods are produced, its chemical constituent is variant, but clinical effectiveness is basic identical.Therefore, the used Sanguis Draxonis of the present invention derives from the plant that four kinds of sections belong to, the i.e. Dracaena cochinchinensis of Liliaceae dracaena (Dracaena cochinchinensis (Lour.) S.C.Chen), Socotra Folium Dracaenae cambodianae (Dracaena ombert Kofchy), long flower Folium Dracaenae cambodianae (Dracaena Angustifolia Roxb.) gos deep into Hainan Folium Dracaenae cambodianae (Dracaena cambodiana Pierre ex Gagn.), bright red Folium Dracaenae cambodianae (Dracaena cinnabari Balf.f), Folium Dracaenae cambodianae (Dracaena draco L.), Arabic Folium Dracaenae cambodianae (Dracaena schizantha Barker), rock palm fibre (Dracaena loureiriGagnepain); The Sanguis Draxonis of Palmae Daemonorops (Daemonorops draco Blume), Malaysia Caulis Fibraureae (Daemonoropspropinquus Becc.), sanguis draconis Caulis Fibraureae (Daemonorops didymoplyllus), Daemonorops motleyei Becc, contain fat Caulis Fibraureae (Daemonorops draconellus Becc), little brightly yellowish rattan (Daemonorops mattanensis Becc); The sanguis draconis Lignum pterocarpi indici of pulse family (Pterocarpus draco L.), Pterocarpus marsupium Roxb, Pterocarpus erinaceus Poiret; The sanguis draconis Fructus Crotonis tree (Croton draco Schlecht) of Euphorbiaceae, Folium Hibisci Fructus Crotonis tree (Croton hibiscifolius Kunth).
(Chen Linfang etc. are found in zoopery, the pharmacodynamic study of Sanguis Draxonis, Yunnan Chinese medicine magazine, 1999,20 (1): 31), Sanguis Draxonis can obviously reduce high viscous state, whole blood viscosity, plasma viscosity and the packed cell volume of " stasis syndrome disease " rabbit blood, increases erythrocyte and platelet electrophoresis speed, suppresses hematoblastic gathering and thrombosis.The herb mixture of Sanguis Draxonis and prescription thereof has been used for thrombotic disease such as cerebral infarction, coronary heart disease, and reliable curative effect is arranged.But the effect of dragon blood for treating coronary heart disease it is believed that it is the Sanguis Draxonis vessel softening, and sclerosis and narrow small artery are had certain contrary soft effect, thereby removes the clinical symptoms of coronary heart disease.To 270 routine upper gastrointestinal hemorrhage patients, all based on hematemesis, have blood in stool.Treatment is with Sanguis Draxonis powder 1g, and every day 4 times is oral, changes every day 2 times, transfusion in right amount simultaneously, non-fasting after changeing into to fecal occult blood is cloudy.The cloudy commentaries on classics time of average fecal occult blood needs 2.4 days, and between 17-48 hour, the consumption 12-30g of Sanguis Draxonis powder, haemostatic effect be (Zhou Hengde etc., Sanguis Draxonis powder treatment upper gastrointestinal hemorrhage 270 examples, Zhejiang Journal of Traditional Chinese Medicine, 1984, (7): 302) very obviously.The active component of Sanguis Draxonis followed up discover, the thrombus model that adopts ligation rat abdomen cardinal vein to cause, total flavones in the observation Sanguis Draxonis is to rat experiment venous thrombosis and ADP, the influence of the platelet aggregation of inductive rat of PAF and rabbit, the result shows, total flavone in Sanguis Draconis (160mg/kg, 80mg/kg, 40mg/kg) irritating stomach has the obvious suppression effect to the rat experiment phlebothrombosis (suppression ratio is respectively 73.53%, 65.77%, 39.75%), to ADP, the inductive platelet aggregation of PAF also has the obvious suppression effect, and be dose-dependence, the prompting total flavone in Sanguis Draconis has the effect of obvious suppression venous thrombosis and platelet aggregation, be the effect of Sanguis Draxonis central vessel active component (Jia Min, total flavone in Sanguis Draconis is to the inhibitory action of experimental phlebothrombosis and external antiplatelet aggregation, Pharmacology and Clinics of Chinese Materia Medica, 2000,16 (3) 18).
Yet Sanguis Draxonis is almost insoluble in distilled water, simulated gastric fluid and the solution below the PH5, and solubilizing agent commonly used can not increase its dissolution, and (study of the Song Dynasty is upright etc., the capsular dissolution of domestic Dragon Blood is investigated Chinese new medicine, 2003,2 (6): 92), human bioavailability is not high.Be actually because the problems of dissolution in aqueous medium has limited the application of Sanguis Draxonis.Therefore develop the drug-supplying system that improves the insoluble drug dissolution and can increase dragon blood for treating cardiovascular and cerebrovascular disease, blood sugar lowering, anti-inflammatory analgesic, antifungal and hemostatic curative effect.
Therefore, the invention reside in and obtain a kind of special solid pharmaceutical dosage formulation that improves dissolution, its purpose is: regardless of the dissolubility of Sanguis Draxonis, with regard to daily dose, make the active component of Sanguis Draxonis can produce enough treatment concentration in vivo as far as possible.
Summary of the invention knows, the solid dispersion effect that not only has immediate effect, and also because the bioavailability of therapeutic component improves, the amount of used therapeutic agent just can reach the therapeutic effect that is equal to the ordinary preparation convention amount under less situation.Application carrier in the solid dispersion has water-solubility carrier, water insoluble carrier and enteric solubility carrier.The water-solubility carrier that usually uses on the medical industry has polyethylene glycols, polyvinylpyrrolidone, poloxamer, organic acid etc.; Water insoluble carrier has ethyl cellulose, wax, lipid to comprise stearic acid and glyceride thereof etc.Water insoluble carrier is generally used for preparing slow release formulation.The solid dispersion technology of preparing is commonly used fusion method, solvent method and solvent melting method.
Chinese patent CN1096852C discloses by mixed method and with water-soluble solid dispersion Sanguis Draxonis has been dispersed into ultrafine particle, used solid dispersion is cyclodextrin or cellulose and derivant thereof, or Polyethylene Glycol, or poloxamer and Myrij class surfactant, and prepare required Sanguis Draxonis fine-particle solid dispersion by dry method or wet grinding method.This technology has increased the dissolution of Sanguis Draxonis in the solid preparation to a certain extent.Dry grinding has the existing shortcoming of prior art, and the size of microgranule is difficult to be well controlled, and this just makes the bioavailability of preparation not control well.Wet grinding is because with an organic solvent, cost height, and be difficult to eliminate organic solvent sometimes, and when solid dispersion contained a small amount of solvent, the crystallization that easily causes medicine changed and reduces the dispersion of principal agent.
In another Chinese patent CN1457835A, narrated with melting method routinely technology prepare the Sanguis Draxonis drop pill.Used substrate has Macrogol 4000, polyethylene glycol 6000, stearic acid, sodium stearate, glycerin gelatine, poloxamer, glyceryl monostearate, hydrogenated vegetable oil, insect wax etc.In this piece prior art, the preparation of Sanguis Draxonis drop pill realizes by Sanguis Draxonis and single carrier matrix, does not provide the scope that is fit to of medicine and carrier, does not also provide the suitable technological parameter such as the temperature controlling scope of preparation process.Generally speaking, in solid dispersion, the dissolution rate of medicine is relevant to the proportional quantities of carrier with medicine, and when making medium carrier with polyethylene glycols, the carrier coupling obviously is better than using the single-matrix carrier to the stripping of medicine.In addition, when fusion method prepared solid dispersion, temperature control was very important condition, the required control temperature difference together of different kinds.Consider the requirement of solid dispersion preparation process, above-mentioned factor is the very important aspect that needs consideration.The Sanguis Draxonis drop pill that water insoluble carrier stearic acid, glyceryl monostearate, hydrogenated vegetable oil and the insect wax that uses in this piece document is used to prepare is to belong to slow release formulation, obviously greatly differs from each other with quick stripping alleged in the document.
Therefore, up to the present, the many schemes that provide in the document all successfully do not find gratifying leaching condition,, can produce the fast Absorption of capacity immediately to reach effective therapeutic effect after dropping into lower medication amount that is.
Fig. 1 illustrates four kinds of oral Sanguis Draxonis dispersible tablets, the i.e. oral Sanguis Draxonis dispersible tablet of handling through micronization technology, with the oral Sanguis Draxonis dispersible tablet of solvent method preparation, the dissolution rate comparison of the oral Sanguis Draxonis dispersible tablet for preparing with the oral Sanguis Draxonis dispersible tablet of single carrier fusion method preparation with the mixed carrier fusion method.The as can be seen from the figure oral Sanguis Draxonis dispersible tablet stripping at the most of micronization technology processing
30% of dosage, and the stripping of the oral Sanguis Draxonis dispersible tablet of solvent method preparation is improved, but also 60% of a stripping dosage.The oral Sanguis Draxonis dispersible tablet of the oral Sanguis Draxonis dispersible tablet of single carrier fusion method preparation and the preparation of mixed carrier fusion method all can make the medicine stripping more than 95%, but the speed of medicine stripping has tangible gap, almost stripping is complete in 20 minutes for the oral Sanguis Draxonis dispersible tablet of mixed carrier fusion method preparation, and the complete stripping of oral Sanguis Draxonis dispersible tablet drug of single carrier fusion method preparation needs 1 hour.
Compare with Fig. 1, Fig. 2 illustrates that four kinds of oral Sanguis Draxonis disperse capsule, promptly the oral Sanguis Draxonis of handling through micronization technology disperses capsule, oral Sanguis Draxonis with the solvent method preparation disperses capsule, oral Sanguis Draxonis with single carrier fusion method preparation disperses capsule and disperses capsule with the oral Sanguis Draxonis that the mixed carrier fusion method prepares, when the ratio of medicine and carrier not simultaneously, the speed difference of its medicine stripping.In Fig. 1, the ratio of medicine and carrier is 40: 60, and the rate of release of medicine is very fast, and in Fig. 2, the ratio of medicine and carrier is 1: 1, and the dissolution rate of medicine slows down, and the ratio that promptly increases carrier can increase the stripping of medicine.Consider the needs of medicine stripping, consider the complexity of administration volume size and preparation process simultaneously again, carrier should guarantee at each preparation enough active component are arranged in the ratio of preparation, to reach therapeutic purposes.
According to the present invention, improve the oral administration solid medicament of dissolution, can obviously improve the bioavailability of Sanguis Draxonis, the invention is characterized in, when oral administration solid medicament of the present invention contacts with aqueous environment (aqueous environment comprises distilled water, simulated gastric fluid and simulated intestinal fluid etc.), Sanguis Draxonis wherein can be fast, stripping completely.Method of the present invention and solid chemicals are specially adapted to the absorption of oral or non-these preparations of orally give and these preparations.Method of the present invention and solid chemicals are applicable to the administration through the aqueous environment of gastrointestinal tract and parenteral route.
Solid chemicals of the present invention comprises as the solid chemicals that is dissolved in treatment cardiovascular and cerebrovascular disease, blood sugar lowering, anti-inflammatory analgesic, antifungal and the anastalsis of the active component in the carrier system, also can comprise other excipient according to the dosage form needs, for example tablet, capsule can absorb fillers, excipient such as disintegrating agent, binding agent, lubricant; But granule absorb fillers, disintegrating agent, binding agent etc.; Powder can add diluent etc.Excipient can account for the 10-90 of oral administration solid medicament weight, and different dosage form proportion difference is bigger, for example, drop pill, the excipient proportion is minimum, and in tablet and granule, the excipient proportion is bigger.
Carrier system in the solid chemicals comprises polyethylene glycol 6000 or Macrogol 4000, component and/or at least a surfactant that at least a water solublity is strong, the polyhydroxy composition that wherein said water solublity is strong is selected from following component alone or in combination: glucose, lactose, mannose, sucrose, sorbitol and xylitol, and wherein said surfactant is Poloxamer188, Poloxamer237, Poloxamer338, Poloxamer407, Poloxamer408, sodium stearate etc.Polyethylene Glycol is under molten condition, and the parallel helical form keys of two of each molecule launch, and component that drug molecule and water solublity are strong or surfactant molecule then enter in the curling chain of carrier and form molecular dispersoid; Polyhydroxy component has stronger hydrogen bond effect, can suppress medicine and separate out crystallization, and component that water solublity is strong when contacting with water or surfactant form hydration shell rapidly on the drug molecule surface in addition, improves the wettability of medicine, quickens the stripping of medicine.
Solid chemicals of the present invention is characterised in that, accounting for the Sanguis Draxonis of total content more than 1% is present in the solid phase of system, the feature of this solid chemicals is that also Sanguis Draxonis is to exist with the solid dispersion form, and the Sanguis Draxonis that exists as solid dispersion is to be scattered in the carrier with molecularity or with colloidal state.The percentage by weight of Sanguis Draxonis and carrier is 1/99 to 100/0.Be preferably 1/0.5 to 1/5, be more preferably 1/1 to 1/2.
The carrier components mixture of solid chemicals, polyethylene glycol 6000 or Macrogol 4000 and hydrophilic component and/or surfactant percentage by weight 1/99 to 100/0.The polyethylene glycol 6000 or the Macrogol 4000 that are preferably about 30-100% mix with hydrophilic component and/or surfactant.The polyethylene glycol 6000 or the Macrogol 4000 that are more preferably about 50-90% mix with hydrophilic component and/or surfactant.
The amount of solid dispersion mixture in solid chemicals that active component and carrier system are formed is about 1 to 100%, decides on different dosage forms.Other materials that constitute solid chemicals are excipient.For example, drop pill mainly is made up of active component and carrier system, 100% of both shared drop pill total amounts; In tablet, active component and carrier system account for the 50-80% of solid chemicals total amount; Active component and carrier system account for the 60-90% of solid chemicals total amount in capsule; Active component and carrier system account for the 10-100% of solid chemicals total amount in granule.
Excipient of the present invention comprises filler: lactose, sucrose, fructose, glucose, mannitol, sorbitol, xylitol, starch, modified starch, pregelatinized Starch, maltodextrin, dextrin, calcium sulfate two water things, calcium hydrogen phosphate, calcium hydrogen phosphate two water things, tricalcium phosphate, calcium carbonate, microcrystalline Cellulose, micropowder cellulose, Powderd cellulose; Binding agent: starch slurry, pregelatinized Starch, arabic gum, sodium alginate, methylcellulose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, polyvinylpyrrolidone, dextrin, gelatin, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, maltodextrin, sorbitol; Disintegrating agent: starch, pregelatinized Starch, carboxymethyl starch sodium, microcrystalline Cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpyrrolidone, crospolyvinylpyrrolidone, silica sol, sodium lauryl sulphate, sodium starch glycolate; Lubricant: stearic acid, magnesium stearate, calcium stearate, glyceryl monostearate, Pulvis Talci, micropowder silica gel, silica sol, microcrystalline Cellulose, Powderd cellulose, sodium benzoate, sodium lauryl sulphate.
The present invention relates to solid chemicals can obtain through the following steps, and it comprises:
A, Sanguis Draxonis and carrier polyethylene glycol 6000 or Macrogol 4000 and hydrophilic component and/or surfactant are prepared into solid dispersion by fusion method;
B, solid dispersion crushing screening obtain to be fit to the particle of size;
C, with above-mentioned acquisition solid dispersion particle and the mixed with excipients that is fit to, make powder or make tablet or be filled into capsule shells and make capsule or make granule or only Sanguis Draxonis and carrier polyethylene glycol 6000 or Macrogol 4000 and hydrophilic component and/or surfactant are prepared into by fusion method and make drop pill or suppository.
The example for preparing solid dispersion with fusion method is as follows: with Sanguis Draxonis and Macrogol 4000 (or 6000) with after hydrophilic component and/or surfactant fully mix; being heated to 50 ℃-80 ℃ makes the complete fusion of mixture (perhaps that dystectic carrier is first with joining after the suitable quantity of water heating for dissolving in the fused liquid; stir evenly); the temperature of mixture is remained on molten condition, fully stir and guarantee that mixture is uniform state.Under agitation be cooled to 0 ℃ rapidly.Dry under vacuum condition, and make temperature return to room temperature gradually, pulverize, sieve.The present invention prepares solid dispersion and is characterised in that melt temperature is no more than 90 ℃.
Another feature of the present invention is that the solid dispersion for preparing can make common, special or new pharmaceutical dosage form and use for medical treatment, and described common pharmaceutical dosage form comprises drop pill, tablet, dispersible tablet, effervescent tablet, capsule, granule, powder, spraying powder, powder, suppository.Various pharmaceutical dosage forms can be by suitable method administration, for example can be through gastrointestinal administration, topical, nose administration, through the lung administration, through ear's administration, transvaginal administration, per rectum administration.
Embodiment
Embodiment 1
Prescription (%g/g)
Sanguis Draxonis 32
Macrogol 4000 (or 6000) 20
Sorbitol 12
Microcrystalline Cellulose 32
Carboxymethyl starch sodium 3
Pulvis Talci 0.6
Micropowder silica gel (or magnesium stearate) 0.4
10% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Preparation method: Sanguis Draxonis, Macrogol 4000 (or 6000), it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add microcrystalline Cellulose → mix homogeneously → 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying (pellet moisture 3%) → granulate → adding carboxymethyl starch sodium that sorbitol → heating and melting (50 ℃--80 ℃) → stir → stir is cooled to 0 ℃ → evacuation down rapidly, Pulvis Talci, micropowder silica gel (or magnesium stearate) → mix homogeneously → tabletting.
Embodiment 2
Prescription (%g/g)
Sanguis Draxonis 45
Macrogol 4000 (or 6000) 30
Lactose (or mannitol) 10
Starch 10
Di Qu Dai Hydroxyalkyl propyl cellulose 2
Carboxymethyl starch sodium 1.5
Pulvis Talci 1
Micropowder silica gel (or magnesium stearate) 0.5
5% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Preparation method: Sanguis Draxonis, it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → adding starch that Macrogol 4000 (or 6000) → heating and melting (50 ℃--80 ℃) → add lactose (or mannitol) aqueous solution → stir → stirs is cooled to 0 ℃ → evacuation down rapidly, Di Qu Dai Hydroxyalkyl propyl cellulose → mix homogeneously → 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying (pellet moisture 3%) → granulate → adding carboxymethyl starch sodium, Pulvis Talci, micropowder silica gel (or magnesium stearate) → mix homogeneously → tabletting.
Embodiment 3
Prescription (%g/g)
Sanguis Draxonis 60
Macrogol 4000 (or 6000) 20
Poloxamer188 15
Di Qu Dai Hydroxyalkyl propyl cellulose 2
Carboxymethyl starch sodium 1.5
Pulvis Talci 1
Micropowder silica gel (or magnesium stearate) 0.5
10% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Preparation method: Sanguis Draxonis, Macrogol 4000 (or 6000), it is dry and make temperature return to room temperature → pulverize → sieve (make particle size be 200 μ m with) → add Di Qu Dai Hydroxyalkyl propyl cellulose → mix homogeneously → 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying (pellet moisture 3%) → granulate → adding carboxymethyl starch sodium that Poloxamer188 → heating and melting (50 ℃--80 ℃) → stir → stir is cooled to 0 ℃ → evacuation down rapidly, Pulvis Talci, micropowder silica gel (or magnesium stearate) → mix homogeneously → tabletting.
Embodiment 4
Prescription (%g/g)
Sanguis Draxonis 36
Macrogol 4000 (or 6000) 26
Poloxamer188 12
Glucose 6
Starch 10
Calcium hydrogen phosphate 7
Carboxymethyl starch sodium 2
Pulvis Talci 0.5
Magnesium stearate) 0.5
10% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Preparation method: Sanguis Draxonis, Macrogol 4000 (or 6000), Poloxamer188, it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add starch that glucose → heating and melting (50 ℃--80 ℃) → stir → stir is cooled to 0 ℃ → evacuation down rapidly, calcium hydrogen phosphate → mix homogeneously → 10% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying (pellet moisture 3%) → granulate → adding carboxymethyl starch sodium, Pulvis Talci, magnesium stearate → mix homogeneously → tabletting.
Embodiment 5
Prescription (%g/g)
Macrogol 4000 (or 6000) 15
Lactose (or mannitol) 5
Starch 16
Cross-linking sodium carboxymethyl cellulose 1.5
Carboxymethyl starch sodium 1.5
Pulvis Talci 0.5
Magnesium stearate) 0.5
10% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Preparation method: Sanguis Draxonis, Macrogol 4000 (or 6000), it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → adding starch that Poloxamer237 → heating and melting (50 ℃--80 ℃) → add lactose (or mannitol) aqueous solution → stir → stirs is cooled to 0 ℃ → evacuation down rapidly, cross-linking sodium carboxymethyl cellulose → mix homogeneously → 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying (granule water 3%) → granulate → adding carboxymethyl starch sodium, Pulvis Talci, magnesium stearate → mix homogeneously → tabletting.
Embodiment 6
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 20
Microcrystalline Cellulose 9
Pulvis Talci 1
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add microcrystalline Cellulose, Pulvis Talci → mix homogeneously → incapsulate that Sanguis Draxonis, Macrogol 4000 (or 6000), Poloxamer338 → heating and melting (50 ℃--80 ℃) → stir → stir are cooled to 0 ℃ → evacuation down rapidly
Embodiment 7
Prescription (%g/g)
Macrogol 4000 (or 6000) 30
Glucose 15
Starch 14
5% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Pulvis Talci 1
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add starch → mix homogeneously → adding 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying (pellet moisture 1%) → granulate → adding Pulvis Talci → mix homogeneously → incapsulate that Sanguis Draxonis, Macrogol 4000 (or 6000), glucose → heating and melting (50 ℃--80 ℃) → stir → stir are cooled to 0 ℃ → evacuation down rapidly.
Embodiment 8
Prescription (%g/g)
Macrogol 4000 (or 6000) 20
Poloxamer338 14
Lactose or mannitol 5
Pulvis Talci 1
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → adding Pulvis Talci → mix homogeneously → incapsulate that Sanguis Draxonis, Poloxamer338, Macrogol 4000 (or 6000) → heating and melting (50 ℃--80 ℃) → add lactose (or mannitol) aqueous solution (lactose or mannitol+water → heating for dissolving) → stir → stirs is cooled to 0 ℃ → evacuation down rapidly
Embodiment 9
Prescription (%g/g)
Poloxamer188 33
Lactose or mannitol 20
Starch 5
Pulvis Talci 2
10% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Preparation method: Sanguis Draxonis, Macrogol 4000 (or 6000), it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add starch → mix homogeneously → adding 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying (pellet moisture 1%) → granulate → adding Pulvis Talci → mix homogeneously → incapsulate that Poloxamer188 → heating and melting (80 ℃) → adding lactose (or mannitol) aqueous solution → stir → stir is cooled to 0 ℃ → evacuation down rapidly.
Embodiment 10
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 45
Xylitol 5
Preparation method: Macrogol 4000 (or 6000), xylitol, Sanguis Draxonis → heating make to splash in the condensing agent (0 ℃) under fusion (50 ℃--80 ℃) → stir → heat-retaining condition and are cooled to ball, collect drop pill, and drying makes drop pill.
Embodiment 11
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 20
Poloxamer188 30
Preparation method: Macrogol 4000 (or 6000), Poloxamer188 Sanguis Draxonis → heating make to splash in the condensing agent (0 ℃) under fusion (50 ℃--80 ℃) → stir → heat-retaining condition and are cooled to ball, collect drop pill, and drying makes drop pill.
Embodiment 12
Prescription (%g/g)
Sanguis Draxonis 30
Glucose 10
Preparation method: Macrogol 4000 (or 6000), glucose, Sanguis Draxonis → heating make to splash in the condensing agent (0 ℃) under fusion (50 ℃--80 ℃) → stir → heat-retaining condition and are cooled to ball, collect drop pill, and drying makes drop pill.
Embodiment 13
Prescription (%g/g)
Macrogol 4000 (or 6000) 40
Poloxamer188 15
Glucose 5
Preparation method: Macrogol 4000 (or 6000), glucose, Sanguis Draxonis, Poloxamer188 → heating make to splash in the condensing agent (0 ℃) under fusion (50 ℃--80 ℃) → stir → heat-retaining condition and are cooled to ball, collect drop pill, and drying makes drop pill.
Embodiment 14
Prescription (%g/g)
Macrogol 4000 (or 6000) 10
Poloxamer188 30
Preparation method: Macrogol 4000 (or 6000), Poloxamer188 Sanguis Draxonis → heating make to splash in the condensing agent (0 ℃) under fusion (50 ℃--80 ℃) → stir → heat-retaining condition and are cooled to ball, collect drop pill, and drying makes drop pill.
Embodiment 15
Prescription (%g/g)
Macrogol 4000 (or 6000) 25
Poloxamer188 10
Sorbitol 5
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) to make powder that Macrogol 4000 (or 6000), sorbitol, Sanguis Draxonis, Poloxamer188 → heating make fusion (50 ℃--80 ℃) → stir → stir be cooled to 0 ℃ → evacuation down rapidly
Embodiment 16
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 15
Lactose (or mannitol) 15
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is below the 200 μ m) that Macrogol 4000 (or 6000), Sanguis Draxonis, Poloxamer188 → heating make fusion (50 ℃--80 ℃) → add lactose (or mannitol) aqueous solution → stir → stirs be cooled to 0 ℃ → evacuation down rapidly, makes powder
Embodiment 17
Prescription (%g/g)
Sanguis Draxonis 30
Macrogol 4000 (or 6000) 10
Poloxamer188 10
Lactose (or mannitol) 15
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) that Macrogol 4000 (or 6000), Sanguis Draxonis, Poloxamer188 → heating make fusion (50 ℃--80 ℃) → stir → stir be cooled to 0 ℃ → evacuation down rapidly, → add lactose (or mannitol) → mix homogeneously, make powder
Embodiment 18
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 30
Preparation method: Macrogol 4000 (or 6000), Sanguis Draxonis, Poloxamer188 → heating make fusion (50 ℃--80 ℃) → bolt mould that stirs → inject, and make suppository
Embodiment 19
Prescription (%g/g)
Macrogol 4000 (or 6000) 35
Sodium stearate 15
Preparation method: Macrogol 4000 (or 6000), Sanguis Draxonis, sodium stearate → heating make fusion (50 ℃--80 ℃) → bolt mould that stirs → inject, and make suppository.
Prescription (%g/g)
Sanguis Draxonis 50
Poloxamer188 45
Glucose 5
Preparation method: Poloxamer188, Sanguis Draxonis, glucose → heating make fusion (50 ℃--80 ℃) → bolt mould that stirs → inject, and make suppository.
Embodiment 21
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 30
Poloxamer188 15
Glucose 5
Preparation method: Macrogol 4000 (or 6000), Sanguis Draxonis, Poloxamer188, glucose → heating make fusion (50 ℃--80 ℃) → bolt mould that stirs → inject, and make suppository
Embodiment 22
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 10
Glucose 30
Soluble starch 10
10% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add soluble starch → mix homogeneously → 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying → granulate that Sanguis Draxonis, Macrogol 4000 (or 6000), glucose → heating and melting (50 ℃--80 ℃) → stir → stir are cooled to 0 ℃ → evacuation down rapidly, makes granule
Embodiment 23
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 10
Glucose 30
Soluble starch 10
10% Gonak is an amount of
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add soluble starch → mix homogeneously → 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying → granulate that Sanguis Draxonis, Macrogol 4000 (or 6000), glucose → heating and melting (50 ℃--80 ℃) → stir → stir are cooled to 0 ℃ → evacuation down rapidly, makes granule
Embodiment 24
Prescription (%g/g)
Macrogol 4000 (or 6000) 10
Poloxamer188 5
Maltodextrin 5
10% polyethylene pyrrole Lip river alkane ketone solution is an amount of
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add maltodextrin → mix homogeneously → 5% polyethylene pyrrole Lip river alkane ketone solution → system wet granular → 50 ℃ aeration-drying → granulate that Sanguis Draxonis, Macrogol 4000 (or 6000), glucose, Poloxamer188 → heating and melting (50 ℃--80 ℃) → stir → stir are cooled to 0 ℃ → evacuation down rapidly, makes granule
Embodiment 25
Prescription (%g/g)
Sanguis Draxonis 50
Macrogol 4000 (or 6000) 20
Poloxamer188 15
Starch 8
Potassium hydrogen tartrate 4
Sodium bicarbonate 1.5
Pulvis Talci 1
Micropowder silica gel (or magnesium stearate) 0.5
10% starch slurry is an amount of
Preparation method: it is dry and make temperature return to room temperature → pulverize → sieve (making particle size is that 200 μ m are following) → add starch → mix homogeneously → be divided into two parts that Sanguis Draxonis, Macrogol 4000 (or 6000), Poloxamer188 → heating and melting (50 ℃--80 ℃) → stir → stir are cooled to 0 ℃ → evacuation down rapidly, a add potassium hydrogen tartrate → mix homogeneously → addings starch slurry in right amount → granulation → drying.
An amount of → granulation → drying that another part adds sodium bicarbonate → mix homogeneously → adding starch slurry.
Granulate → mix homogeneously → Pulvis Talci, micropowder silica gel (or magnesium stearate) → mix homogeneously → tabletting behind two kinds of particle dryings.
Claims (9)
1, comprise treatment cardiovascular and cerebrovascular disease as miscible active component in carrier system, blood sugar lowering, anti-inflammatory analgesic, the solid chemicals of antifungal and anastalsis, described carrier system polyethylene glycol 6000 or Macrogol 4000, at least a water-soluble component and/or at least a surfactant, wherein said water soluble ingredient is selected from following component alone or in combination: glucose, lactose, mannose, sucrose etc., and wherein said surfactant is Poloxamer188, Poloxamer237, Poloxamer338, Poloxamer407, Poloxamer408.
2, according to the desired solid chemicals that improves dissolution of claim 1, wherein, the percentage by weight of described active component and carrier system is 1/99 to 100/0.
3, according to the percentage by weight of the carrier system polyglycols 6000 of right 1 and the 2 desired solid chemicals that improve dissolution or Macrogol 4000 and water-soluble component and/or surfactant 1/99 to 100/0.
4, according to the described method of claim 1 to 3, wherein, the active component of described treatment cardiovascular and cerebrovascular disease, blood sugar lowering, anti-inflammatory analgesic, antifungal and anastalsis is the extractive of general flavone of Sanguis Draxonis and Sanguis Draxonis.
5, according to the described Sanguis Draxonis of claim 1 to 4 and total flavone in Sanguis Draconis extract resin: i.e. the Dracaena cochinchinensis of Liliaceae dracaena (Dracaena cochinchinensis (Lour.) S.C.Chen) from following section platymiscium, Socotra Folium Dracaenae cambodianae (Dracaena ombert Kofchy), long flower Folium Dracaenae cambodianae (Dracaena Angustifolia Roxb.) gos deep into Hainan Folium Dracaenae cambodianae (Dracaena cambodiana Pierre ex Gagn.), bright red Folium Dracaenae cambodianae (Dracaena cinnabari Balf.f.), Folium Dracaenae cambodianae (Dracaena draco L.), Arabic Folium Dracaenae cambodianae (Dracaena schizantha Barker), rock palm fibre (Dracaena loureiriGagnepain); The Sanguis Draxonis of Palmae Daemonorops (Daemonorops draco Blume), Malaysia Caulis Fibraureae (Daemonoropspropinquus Becc.), sanguis draconis Caulis Fibraureae (Daemonorops didymoplyllus), Daemonorops motleyei Becc, contain fat Caulis Fibraureae (Daemonorops draconellus Becc), little brightly yellowish rattan (Daemonorops mattanensis Becc); The sanguis draconis Lignum pterocarpi indici of pulse family (Pterocarpus draco L.), Pterocarpus marsupium Roxb, Pterocarpus erinaceusPoiret; The sanguis draconis Fructus Crotonis tree (Croton draco Schlecht) of Euphorbiaceae, Folium Hibisci Fructus Crotonis tree (Croton hibiscifoliusKunth).
6, the solid chemicals that requires according to claim 1 to 5, earlier active component and carrier polyethylene glycol 6000 or Macrogol 4000 are prepared into solid dispersion with water-soluble component and/or surfactant by fusion method, make common, special or new with mixed with excipients then for medical use pharmaceutical dosage form.Wherein, the amount in the carrier mixture oral solid medicament in described active component and the solid dispersion is about 1 to 100%.
7, the solid chemicals that requires according to claim 1 to 6, the preparation process feature of solid dispersion are that melt temperature is no more than 90 ℃ (perhaps that dystectic carrier is first with joining in the fused liquid after the suitable quantity of water heating for dissolving, as to stir evenly); Keep certain hour and abundant the stirring to guarantee to be uniform state in the molten condition temperature; Under agitation be cooled to 0 ℃ rapidly, prevent molecular aggregates and crystalline formation; Dry under vacuum condition, and make temperature return to room temperature gradually, guarantee that the solid dispersion that forms is stable and be easy to pulverizing.
8, according to right 1 to the 7 desired dosage form of improving the solid chemicals of Sanguis Draxonis dissolution, comprise drop pill, tablet, dispersible tablet, effervescent tablet, capsule, granule, powder, spraying powder etc.
9, according to the described method of arbitrary claim in the right 1 to 8, it is identical or be low to moderate general formulation dosage 1/6th to it is characterized in that being used for the treatment of the dosage of cardiovascular and cerebrovascular disease, blood sugar lowering, anti-inflammatory analgesic, antifungal and hemostatic dosage every day and general formulation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410027277 CN1698680A (en) | 2004-05-21 | 2004-05-21 | Drug giving system for improving resina draconis dissolution |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410027277 CN1698680A (en) | 2004-05-21 | 2004-05-21 | Drug giving system for improving resina draconis dissolution |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1698680A true CN1698680A (en) | 2005-11-23 |
Family
ID=35475031
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410027277 Pending CN1698680A (en) | 2004-05-21 | 2004-05-21 | Drug giving system for improving resina draconis dissolution |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1698680A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101385717B (en) * | 2007-09-13 | 2013-06-26 | 天津药物研究院 | Solid dispersion containing sofalcone as active ingredient and preparation method thereof |
| CN104666265A (en) * | 2015-03-17 | 2015-06-03 | 常州康普药业有限公司 | Promethazine hydrochloride tablet and preparation method thereof |
| CN104997752A (en) * | 2015-06-30 | 2015-10-28 | 陈晓芳 | Resina draconis rapid release capsule, and preparation method thereof |
-
2004
- 2004-05-21 CN CN 200410027277 patent/CN1698680A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101385717B (en) * | 2007-09-13 | 2013-06-26 | 天津药物研究院 | Solid dispersion containing sofalcone as active ingredient and preparation method thereof |
| CN104666265A (en) * | 2015-03-17 | 2015-06-03 | 常州康普药业有限公司 | Promethazine hydrochloride tablet and preparation method thereof |
| CN104666265B (en) * | 2015-03-17 | 2018-04-13 | 常州康普药业有限公司 | A kind of promethazine hydrochloride tablet and preparation method thereof |
| CN104997752A (en) * | 2015-06-30 | 2015-10-28 | 陈晓芳 | Resina draconis rapid release capsule, and preparation method thereof |
| CN104997752B (en) * | 2015-06-30 | 2018-07-20 | 陈晓芳 | A kind of Resina Draconis quick-release capsules and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN88101104A (en) | Medicine tablet, medicine granule and preparation method thereof | |
| CN1939378A (en) | Preparation of blood-activating and pain-stopping capsules | |
| CN1527700A (en) | Compaction process for manufacture of sodium phenytoin dosage form | |
| CN1745797A (en) | Medicine for treating menstrual irregularities and menalgia | |
| CN1698680A (en) | Drug giving system for improving resina draconis dissolution | |
| CN1723964A (en) | Medicine for treating cough and chronic bronchitis | |
| CN1695711A (en) | Diphase capsule of compound dalbergia wood and preparation method | |
| CN1593634A (en) | Blood nourishing, brain refreshing orally disintegrating tablet and its preparation process | |
| CN1840196A (en) | Dispersible preparation adaptable to indissoluble drug | |
| CN1679901A (en) | Compound preparation of Jianganling for liver and its making method | |
| CN1698714A (en) | 'Rukuaixiao' preparation for treating mammary disease and its preparation process | |
| CN1813984A (en) | Chinese medicine preparation for treating liver disease and preparing method | |
| CN1733251A (en) | Sugar reducing preparation for curing diabetes and its complication comprising astragalus root and leech and process for preparing the same | |
| CN1814110A (en) | Medicine for treating gynecophathy | |
| CN1736411A (en) | Pharmaceutical preparation with functions of clearing heat, removing dampness and benefiting gallbladder | |
| CN1626076A (en) | Andrographolide drop pills and preparation method | |
| CN1626211A (en) | Astragalus-leech preparation of lowering blood sugar for treating diabetes and syndrome and preparation method | |
| CN1309398C (en) | Orally disintegrating tablet for treating cardiovascular diseases and its preparing process | |
| CN1781479A (en) | Chinese small iris seed agent dispersion system and its preparing method | |
| CN1742936A (en) | Natural medicine preparation for treating diabets and preparing method | |
| CN1742808A (en) | Medicine composition with synergetic function | |
| CN1872232A (en) | Composition of medication for curing cerebrovascular disease, and preparation method | |
| CN1631358A (en) | Compound pseudoephedrine hydrochloric acid containing powder for treating cold, its prescription and preparation method | |
| CN1586586A (en) | Chinese medicine preparation for treating urinary system infection and its preparing method | |
| CN1616018A (en) | Preparation for improving bioavailability and medicine effect for treating gynecopathy and preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Jin Miaozhen Document name: Notification before expiration of term |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Jin Miaozhen Document name: the First Notification of an Office Action |
|
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Jin Miaozhen Document name: Deemed as a notice of withdrawal (Trial) |