CN1939416A - Douricine drop pills and preparation thereof - Google Patents
Douricine drop pills and preparation thereof Download PDFInfo
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- CN1939416A CN1939416A CN 200610152664 CN200610152664A CN1939416A CN 1939416 A CN1939416 A CN 1939416A CN 200610152664 CN200610152664 CN 200610152664 CN 200610152664 A CN200610152664 A CN 200610152664A CN 1939416 A CN1939416 A CN 1939416A
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Abstract
A dripping pill of asiatic moonseed rhizome is prepared from asiatic moonseed rhizome through proportional adding polyoxyvinyl monostearate, mixing, heating for fusing, stirring, and dripping in condensing liquid.
Description
[technical field] the present invention relates to a kind of medicine and preparation method thereof, particularly Douricine drop pills and preparation method thereof.
[background technology]
Drop pill splashes in the immiscible condensed fluid after being meant solid or liquid medicine and substrate heat fused mixing, and condensation is shunk and the preparation made.Because medicine is with superfine microparticulate, and the one-tenth colloid disperses in solution, and becomes rapid dissolved amorphous mixture, can improve the drug oral bioavailability effectively.The Rue oil. drop pill of China with regard to going on the market in 1971 makes dropping pill formulation really become a kind of effective pharmaceutical dosage form.Drop pill can also can be made into sustained-release preparation for for oral administration, external and local the use, has brought into play and continued playing an important role in China's field of pharmaceutical preparations, is a kind of noticeable and the dosage form of good development prospect arranged.
Dropping pill formulation has the multiple advantage that is different from other peroral dosage forms, by selecting water-soluble base for use, control drug release rate or dissolve scattered time limit, can under the condition of quenching, form solid dispersion, medicine exists with atomic little microgranule, crystallite or molecularity, so can improve the dissolution rate and the bioavailability of insoluble drug, play quick-acting, effect efficiently; Select for use suitable controlled slowly releasing adjuncts or enteric solubility substrate to drip and make ball, can control the release of medicine, play the effect of slow release or enteric.Particularly, when its sustained-release preparation of preparation, can consider drops, thereby can in control drug release, increase bioavailability for some insoluble drugs or drugs with low bioavailability.The production equipment of dropping pill formulation is simple, processing ease, and weight differential is little, and production cost is low, and no dust is suitable for industrialized great production.Also facile hydrolysis, oxidation decomposition or volatile pharmaceutical pack can be embedded in wherein and increase stability of drug.
According to its preparation technology's difference, dropping pill formulation can be divided into quick-acting efficient drop pill, controlled release pill, enteric coated drop pill, coated drop pill, external-use drops, hard capsule drop pill, elaioplast drop ball etc.Used substrate is except fat-soluble substrate (as stearic acid, glyceryl monostearate, insect wax, hydrogenated vegetable oil, stearyl alcohol, spermol, semi-synthetic fatty acid ester etc.) and water-soluble base (as Polyethylene Glycol, sodium stearate, glycerin gelatine, carbamide, poloxamer etc.) commonly used, in recent years, there are some good polymeric materials to be developed substrate again as drop pill, and the more and more important effect of performance.Polyoxyethylene stearate 40 esters are a kind of nonionic surfactant, be usually used in preparing insoluble drug, solid dispersion as griseofulvin, tolbutamide and nalidixan etc., it has similar average molecular mass to PEG2000, and S-40 can promote dispersion, disintegrate, the stripping of medicine in solid dispersion and the effect that makes medicament solubilization.Along with being on the increase of substrate kind, preparation technology's is ripe day by day perfect, and drop pill is extensive day by day in the application of Chinese-western medicine preparation, therefore existing medicine is carried out modified form, produce more medicinal dropping ball dosage form, will greatly enrich drug market, improve quality of medical care.
Rhizoma Menispermi (Rhizoma Menispermi) is the dry rhizome of menispermaceous plants Caulis menispermi Menispermum dauricumDC..Bitter in the mouth, cold in nature, slightly poisonous.Return lung, stomach, large intestine channel.Heat-clearing and toxic substances removing, reducing swelling and alleviating pain effect are arranged.Be used for laryngopharynx swelling and pain, cough due to lung-heat, heat-clearing and toxic substances removing, wind-expelling pain-stopping, enteritis and dysentery, rheumatic arthralgia.Contain multiple alkaloid in the Rhizoma Menispermi rhizome, the alkaloid of telling in the inferior and Japanese product Radix Sophorae Tonkinensis of Berli has westerly: dauricine (Dauricine), dauricinoline (Daurinoline), different dauricinoline (Dauricinol-ine), dauricoline (Dauricoline), magnoflorine (Magnoflorine), Dauricine (Menisperine), acutumine (Acutumine), N-Noracutumine (Acutumidine), sinomenine (sinomenine Sinomenine), Cheilanthifoline alkali (Cheilanthifoline), stepharine (Stephairne) and stepholidine (Stephol-idine).
Dauricine can reduce arteriotony, increases heart contraction amplitude and cholinolytic and spasmolysis.Can reduce the level of cholesterolemia.For the hypertensive patient, can cause that significant blood pressure reduces.Also have cough-relieving, phlegm-dispelling functions, and can resist the tic that acetyl chloride alkali causes.Sinomenine has cholinolytic and spasmolysis, can analgesia, antiinflammatory, calmness, analgesic and blood pressure lowering, and can alleviate the anaphylactic reaction of dog and mice.Rhizoma Menispermi is to staphylococcus aureus, Hemolytic streptococcus, Diplococcus pneumoniae, meningococcus, bacillus enteritidis, dysentery bacterium, typhoid fever and pay common pathogenic dermatophytes such as Bacillus typhi, red mentagrophytes and Candida albicans etc. antibacterial action is arranged.
The Rhizoma Menispermi of using clinically is tablet, syrup, granule, capsule at present.Dropping pill formulation has characteristics such as bioavailability height, release fast, quick produce effects, is made into drop pill, in the hope of reaching the raising bioavailability, brings into play curative effect of medication more fully, reduces purposes such as untoward reaction.
[summary of the invention]
The purpose of this invention is to provide drops of a kind of Rhizoma Menispermi and preparation method thereof.
With the Rhizoma Menispermi is primary raw material, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, filter, merging filtrate leaves standstill, and gets supernatant concentration, concentrate is a Rhizoma Menispermi extract, according to certain ratio, add substrate such as surfactant polyethylene then, be prepared from through specific technology, apparatus processing again.
The present invention studies by experiment Rhizoma Menispermi has been carried out modified form, changes dropping pill formulation into from existing tablet, syrup, granule, capsule.Utilize substrate such as surfactant polyethylene, polyoxyethylene monostearate, polyoxyethylene stearate 40 esters, polyethers and selected medicine material to make solid dispersion; making medicine be molecule, colloid or microcrystalline state is scattered in the substrate; the total surface area of medicine increases; and substrate is hydrophilic; medicine had wetting action; can make that medicine is rapidly molten to loose into microgranule or solution, thereby make the dissolving of medicine and absorb and accelerate.Thereby improved bioavailability and stability of drug, produced efficient, convenient etc. effect.
Wherein said dropping pill formulation is made up of Rhizoma Menispermi extract and substrate, and wherein the weight ratio of Rhizoma Menispermi extract and substrate is 1: 1～15.Described substrate includes Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers one or more composition.Substrate is following but be not limitation of the invention for more than one mixture of ingredients exemplify: polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1～10; Betacyclodextrin: Polyethylene Glycol=1: 1～10; Poloxamer: Polyethylene Glycol=1: 1～10; Carboxymethyl starch sodium: Polyethylene Glycol=1: 1～10.
Wherein said drop pill can be made into common dropping pill formulation, also can be made into slow-release pill preparation, enteric coated drop pill preparation, coated drop pill preparation etc.
A kind of preparation method provided by the present invention is as follows:
With the Rhizoma Menispermi is primary raw material, according to certain ratio, adds substrate such as surfactant polyethylene, is prepared from through specific technology, apparatus processing again.Specific as follows:
(1) prescription: Rhizoma Menispermi extract+substrate;
Substrate: include Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers one or more composition.
The weight ratio of Rhizoma Menispermi and substrate is 1: 1～15;
(2) preparation technology: concrete implementation step is as follows:
The first step is mixed Rhizoma Menispermi according to certain ratio with matrix phase; Substrate can be Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), in polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers etc. any one or a few mix mutually.
Second step was adopted water-bath, oil bath or other mode of heating, and mixed material is heated to fusion, stirred.
The 3rd step inserted on the drop pill machine, and keeping temperature is 70～120 ℃.
The 4th step was selected sizeable drip nozzle, with suitable speed, splashed in 40 →-15 ℃ the condensing agent; Condensing agent can be any one or a few in liquid paraffin, methyl-silicone oil, the vegetable oil.
The 5th step type to be shrunk to takes out, and removes the surface condensation agent, drying.
The Douricine drop pills preparation that [beneficial effect] is involved in the present invention; utilize substrate such as surfactant polyethylene, polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid and medicine material to make solid dispersion; making medicine be molecule, colloid or microcrystalline state is scattered in the substrate; the total surface area of medicine increases; and substrate is hydrophilic; medicine had wetting action; can make that medicine is rapidly molten to loose into microgranule or solution, thereby make the dissolving of medicine and absorb and accelerate.Thereby improved bioavailability, performance is efficient, Stabilization etc.
Compare with the administering mode of tablet, exist essential distinction.Drop pill with the solid dispersion technology preparation can adopt oral and sublingual administration, and effective ingredient is fully contacted with mucomembranous surface, absorbs by mucomembranous epithelial cell, directly enters blood circulation.Especially sublingual administration administration can directly enter blood circulation without gastrointestinal tract and liver, has avoided first pass effect effectively, thereby it is rapid to have an onset, bioavailability height, characteristics such as side effect is little, and medication is convenient.
1. compare with oral tablet, this preparation not only can be oral, but sublingual administration still, this just overcome the tablet onset slowly, shortcoming such as low, the gastrointestinal irritation of liver sausage first pass effect, bioavailability.
2. this dropping pill formulation volume is little, in light weight, more is applicable to and carries.After containing entrance cavity, contact promptly with saliva and to dissolve rapidly, and absorb by oral mucosa, not only rapid-action, and the influence of not taken food, promptly all can containing take after meal ante cibum.
3. the contained drug dose of each drop pill of this preparation is accurate, and the patient who is suitable for the different state of an illness, all ages and classes more flexibly and accurately grasps dosage.
4. the production process equipment for preparing this preparation-drop pill is simple, easy to operate; Operation is few, with short production cycle, automaticity is high, labor intensity is low, production efficiency is high; Workshop does not have dust, helps labor protection and environmental protection; The preparation drop pill need adopt high-tech means and equipment, and principal agent is uniformly dispersed in substrate, and dosage is accurate, and the ball method of double differences is different little than tablet; Production cost is lower than with below 50% of kind tablet.
5. this preparation is by after the heating of solid drugs and substrate, being melt into liquid state, splashes into to make in the not miscible condensed fluid.Therefore, the stability of drug height, not facile hydrolysis, oxidation, and the operation be under liquid state, to carry out, no dust pollution is not subject to the influence of crystal formation, thereby has guaranteed the quality of medicine, has increased stability.
[specific implementation method]
By following concrete embodiment, can further understand the present invention, but following example not a limitation of the invention.
The preparation of embodiment 1-Douricine drop pills (1)
Method: taking polyethylene glycol 2,000 0.1 restrains respectively, Macrogol 4000 13 grams, polyethylene glycol 6000 23.5 grams, Polyethylene Glycol 8,000 0.1 grams, cetomacrogol 1000 0 0.1 grams, polyoxyethylene stearate 40 esters 1 gram, betacyclodextrin 0.5 gram, poloxamer 0.5 gram, carboxymethyl starch sodium 0.5 gram, stearic acid 0.1 gram, sodium stearate 0.1 gram, glycerin gelatine 0.1 gram, glyceryl monostearate 0.1 gram, Lac 0.1 gram, polyoxyethylene monostearate 0.1 gram, polyethers 0.1 gram, mix homogeneously, add Rhizoma Menispermi extract 10 grams again, fully mix, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, adopt homemade special drilling pill machine, regulate its water dropper temperature and make it remain on 85 ℃ (error＜2%); With the methyl-silicone oil is condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 20 →-5 ℃ (error＜5%), again according to the given method of the front preparation technology system of dripping, wait to take out behind the type of being shrunk to, remove the surface condensation agent, drying is made the drop pill that the heavy 50mg of ball contains medicine 10mg/ grain, carry out then rounding rate (%), dissolve scattered time limit (minute), the mensuration of the ball method of double differences different (%) and hardness, the results are shown in Table 1.
The testing result of table 1, Douricine drop pills (1)
| Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness is qualified |
| 85 | 3-6 | 5 | Qualified |
The preparation of embodiment 2-Douricine drop pills (2)
Method: taking polyethylene glycol 4,000 10 grams, polyethylene glycol 6000 20 grams, polyoxyethylene stearate 40 esters 3 restrain respectively, betacyclodextrin 6 restrains, glyceryl monostearate 1 gram, mix homogeneously, add Rhizoma Menispermi extract 10 grams again, fully mix, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, adopt homemade special drilling pill machine, regulate its water dropper temperature and make it remain on 85 ℃ (error＜2%); With the methyl-silicone oil is condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 20 →-5 ℃ (error＜5%), again according to the given method of the front preparation technology system of dripping, wait to take out behind the type of being shrunk to, remove the surface condensation agent, drying is made the drop pill that the heavy 50mg of ball contains medicine 10mg/ grain, carry out then rounding rate (%), dissolve scattered time limit (minute), the mensuration of the ball method of double differences different (%) and hardness, the results are shown in Table 2.
The testing result of table 2, Douricine drop pills (2)
| Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness is qualified |
| 84 | 3-5 | 4 | Qualified |
The preparation of embodiment 3-Douricine drop pills (3)
Method: taking polyethylene glycol 4,000 11 grams, polyethylene glycol 6000 29 restrain respectively, mix homogeneously, add Rhizoma Menispermi extract 10 grams again, fully mix, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, adopt homemade special drilling pill machine, regulate its water dropper temperature and make it remain on 85 ℃ (error＜2%); With the methyl-silicone oil is condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 20 →-5 ℃ (error＜5%), again according to the given method of the front preparation technology system of dripping, wait to take out behind the type of being shrunk to, remove the surface condensation agent, drying is made the drop pill that the heavy 50mg of ball contains medicine 10mg/ grain, carry out then rounding rate (%), dissolve scattered time limit (minute), the mensuration of the ball method of double differences different (%) and hardness, the results are shown in Table 3.
The testing result of table 3, Douricine drop pills (3)
| Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness is qualified |
| 86 | 4-5 | 4 | Qualified |
The preparation of embodiment 4-Douricine drop pills (4)
Method: taking polyethylene glycol 6,000 30 grams, ethylene glycol 4,000 7 grams, poloxamer 3 restrain respectively, mix homogeneously, add Rhizoma Menispermi extract 10 grams again, fully mix, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, adopt homemade special drilling pill machine, regulate its water dropper temperature and make it remain on 85 ℃ (error＜2%); With the methyl-silicone oil is condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 20 →-5 ℃ (error＜5%), again according to the given method of the front preparation technology system of dripping, wait to take out behind the type of being shrunk to, remove the surface condensation agent, drying is made the drop pill that the heavy 50mg of ball contains medicine 10mg/ grain, carry out then rounding rate (%), dissolve scattered time limit (minute), the mensuration of the ball method of double differences different (%) and hardness, the results are shown in Table 4.
The testing result of table 4, Douricine drop pills (4)
| Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness is qualified |
| 86 | 3-5 | 5 | Qualified |
The preparation of embodiment 5-Douricine drop pills (5)
Method: taking polyethylene glycol 6,000 17 grams, ethylene glycol 4,000 20 grams, betacyclodextrin 3 restrain respectively, mix homogeneously, add Rhizoma Menispermi extract 10 grams again, fully mix, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, adopt homemade special drilling pill machine, regulate its water dropper temperature and make it remain on 85 ℃ (error＜2%); With the methyl-silicone oil is condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 20 →-5 ℃ (error＜5%), again according to the given method of the front preparation technology system of dripping, wait to take out behind the type of being shrunk to, remove the surface condensation agent, drying is made the drop pill that the heavy 50mg of ball contains medicine 10mg/ grain, carry out then rounding rate (%), dissolve scattered time limit (minute), the mensuration of the ball method of double differences different (%) and hardness, the results are shown in Table 5.
The testing result of table 5, Douricine drop pills (5)
| Rounding rate (%) | Dissolve scattered time limit (minute) | The ball method of double differences different (%) | Hardness is qualified |
| 87 | 4-5 | 6 | Qualified |
Claims (4)
1. Douricine drop pills is characterized in that described drop pill is made up of the Rhizoma Menispermi extract and the substrate that contain as active constituents of medicine, its proportioning with weight portion count 1: 1～15.
2. dropping pill formulation according to claim 1 is characterized in that: described substrate includes Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers one or more composition.
3. the preparation method that is used for the described Douricine drop pills of claim 1 is characterized in that being made of following step:
Step 1 is according to 1: the ratio of (1～15), promptly get a Rhizoma Menispermi raw material, and mix with 1 part to 15 parts matrix phase, its mesostroma is by Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), in polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers substrate any one or a few mix mutually;
Step 2 adopts water-bath, oil bath or other mode of heating, and mixed material is heated to fusion, stirs;
Step 3 is inserted special-purpose drop pill machine, and adjustment water dropper temperature is 70～120 ℃;
Step 4 is selected sizeable drip nozzle, with suitable speed, splashes in 40 →-15 ℃ the condensing agent; Condensing agent can be any one in liquid paraffin, methyl-silicone oil, the vegetable oil;
Step 5 type to be shrunk to takes out, and removes the surface condensation agent, drying, and packing, promptly.
4. according to the step 3 of the described preparation method of claim 4, it is characterized in that: the preferred scope of temperature of dripping dropping-pill machine head in the system process is 80～100 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610152664 CN1939416A (en) | 2005-09-26 | 2006-09-25 | Douricine drop pills and preparation thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510104992 | 2005-09-26 | ||
| CN200510104992.3 | 2005-09-26 | ||
| CN 200610152664 CN1939416A (en) | 2005-09-26 | 2006-09-25 | Douricine drop pills and preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1939416A true CN1939416A (en) | 2007-04-04 |
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ID=37958118
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610152664 Pending CN1939416A (en) | 2005-09-26 | 2006-09-25 | Douricine drop pills and preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1939416A (en) |
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2006
- 2006-09-25 CN CN 200610152664 patent/CN1939416A/en active Pending
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