CN1255098C - Ophiopogonin enteric coated microsphere preparation and preparing process thereof - Google Patents
Ophiopogonin enteric coated microsphere preparation and preparing process thereof Download PDFInfo
- Publication number
- CN1255098C CN1255098C CN 200310109428 CN200310109428A CN1255098C CN 1255098 C CN1255098 C CN 1255098C CN 200310109428 CN200310109428 CN 200310109428 CN 200310109428 A CN200310109428 A CN 200310109428A CN 1255098 C CN1255098 C CN 1255098C
- Authority
- CN
- China
- Prior art keywords
- preparation
- ophiopogonin
- meant
- enteric
- coated microsphere
- 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 relates to an enteric coated microsphere ophiopogonin preparation and a preparation method thereof. The enteric coated microsphere preparation has a formulation composition by weight percentage: 5% to 20% of ophiopogon root total saponin extract, 20% to 40% of macromolecule capsule wall material, 20% to 40% of anti-sticking agent and 10% to 30% of plasticizing agent. The preparation of the present invention solves the problem of the existing ophiopogonin preparation, improves the medication elasticity of a patient, reduces the irrigation to the gastric mucosa, and realizes targeted delivery of drugs.
Description
Technical field:
The present invention relates to the Chinese medicine preparation technical field, be specifically related to ophiopogonin enteric-coated microsphere preparation and preparation method.
Background technology:
Be traditional Chinese medical science medicine commonly used Radix Ophiopogonis, has nourishing YIN and moistening the lung, reinforcing stomach reg fluid, an effect of the relieving restlessness that clears away heart-fire.Have injection Radix Ophiopogonis clinically, the oral liquid that nourishes heart etc. is applied to the treatment of coronary heart disease.Modern pharmacological research shows that the main effective ingredient for the treatment of coronary heart disease Radix Ophiopogonis is a steroidal saponin.Its aglycon is divided into: Luo Sikao sapogenin (ruscogenin), (23s, 24s, 25s, )-23,24 dihydroxy sieve scott sapogenin [(23s, a 24s, 25s)-23,24-dih-ydroxyruscogenin], diosgenin (diosgenin), aglycon Radix Ophiopogonis (ophiogenin) etc.Clinical Chinese patent medicine commonly used has DIAOXINXUE KANG JIAONANG, and its effective ingredient is the dioscorea panthaica total saponin, also belongs to steroid saponin, and its aglycon is divided into diosgenin.Because of its price is comparatively cheap, favored by the patient, but the untoward reaction of more crowd's GI irritation is arranged, clinical practice is limited to a certain extent.
Summary of the invention:
Technical problem to be solved by this invention is to improve the ophiopogonin preparation, and a kind of patient's of improvement medication compliance is provided, and reduces the gastric mucosa zest, realizes the novel ophiopogonin enteric-coated microsphere preparation of preparation targeted delivery of drugs.
The percentage by weight prescription of ophiopogonin enteric-coated microsphere preparation disclosed by the invention consists of Radix Ophiopogonis total saponins extract 5-20%, high score ascus material 20-40%, antitackiness agent 20-40% and plasticizer 10-30%.The ophiopogonin enteric-coated microsphere is observed particle diameter about 10-50 μ m under electron-microscope scanning.
Wherein said Radix Ophiopogonis total saponins extract is meant that ophiopogonin content that the water extract of raw medicinal herbs Radix Ophiopogonis obtains is greater than 60% extract behind purification by macroporous resin.
High score ascus material of the present invention is meant acrylic resin II, hydroxypropylmethyl cellulose phthalate.
Antitackiness agent of the present invention is meant micropowder silica gel, Pulvis Talci.
Plasticizer of the present invention is meant Oleum Ricini, glycerol, O-phthalic acid diacid ester.
Another technical problem to be solved by this invention is to disclose the preparation method of above-mentioned ophiopogonin enteric-coated microsphere preparation.
The preparation method of ophiopogonin enteric-coated microsphere preparation disclosed by the invention comprises the following steps:
Measure the capsule material with dissolution with solvents and be made into 2-4%w/v concentration by prescription, the Radix Ophiopogonis total saponins extract is dissolved in the capsule material solution, making the spice ratio is 1: 1-8, preferred 1: 2-4, add plasticizer, stir, add antitackiness agent again, under agitation carry out spray drying, promptly.Microspherulite diameter can according to dosage require directly to be filled into and make tablet after the glue shell is made capsule or tabletting about 10-50 μ m.
Solvent described in the preparation method of the present invention is meant ethanol or the methanol of 85-95%.
The process conditions of spray drying method of the present invention are meant inlet temperature 70-90 ℃, leaving air temp 50-70 ℃, and nebulizer rotating speed 30-50RPM, charging rate 10-30ml/min.
It is a physical process that spray drying prepares microsphere, and it is lower to the requirement of equipment, and technological parameter (inlet temperature, leaving air temp, atomization speed, charging rate etc.) is easily controlled.Because the medicinal liquid that preparation can be finished is input to certain speed in the airtight relatively system through constant flow pump and carries out spray drying; need not to add all ingredients, adjuvant midway; therefore there is not midway operations such as shutting down, dismantle, stir, leave standstill; only need after preparation is finished; the taking-up of powder in the catcher is got final product, and it is very easy therefore to operate.The solvent that spray drying touched is except ethanol, acetone and other organic solvent, major part is a water, life-time service can not cause corrosion to equipment, do not resemble other chemical methodes (as coacervation, solvent evaporation method etc.) and in preparation process, will transfer pH, add firming agent, add different solvents etc., therefore help industrialized great production, this is that spray drying prepares the big advantage of microcapsule with respect to additive method.
In earlier stage the intestinal flora metabolic conversion exsomatizes, all proves in the body experiment, ophiopogonin OD ' can be metabolised to diosgenin under the effect of rat intestinal flora, and finally in urine, also detect diosgenin, infer that thus ophiopogonin OD ' enters blood at digestive tract with its aglycon form absorption.Make behind the enteric-coated microsphere preparation medicine disintegrate but not stripping under one's belt, under specific pH environment, begin to discharge ophiopogonin after entering into intestinal.Because the saponin molecular weight is big, water solublity is strong, be difficult for seeing through the intestinal wall biomembrane, and it is little to change into molecular weight after the metabolism of Enterobacter cloaca, and fat-soluble bigger secondary glycoside and aglycon composition, again through being absorbed into blood, thus the performance drug effect.
Common enteric coated preparation is the skin parcel enteric material at medicine, after medicine enters human body, discharges rapidly at intestinal, easily causes the local excitation of medicine to intestinal.And being form with enteric-coated microsphere, enteric-coated microsphere preparation of the present invention is present in the preparation, after medicine enters human body in the stomach disintegrate but not stripping, entering behind the intestinal is progressively stripping of unit again with the microsphere, make whole medicine process in leaching even, not only avoided medicine gastrointestinal to be stimulated but also guaranteed the absorption of medicine.
The ophiopogonin enteric-coated microsphere that makes with the inventive method carries out release research in gastric mucosa irritant experiment and the acid, and the result is as follows:
1. gastric mucosa irritant experiment
Get 18 of rats, divide 3 groups at random, the microsphere group gives the ophiopogonin enteric-coated microsphere, dosage be 343.64mg/kg days (in diosgenin, be 18.90mg/kg days), it is the Radix Ophiopogonis total saponins extract that the saponin group gives dosage, dosage is 54.00mg/kg days (in diosgenin, being 18.90mg/kg days), and matched group gives the equivalent normal saline, continuous irrigation stomach 5 days, free during this time diet drinking-water is put to death behind the 1h after the last administration, dissects and gets stomach, anatomic microscope is observed the gastric mucosa injury situation, and does the pathology section.
Observe according to anatomical lens, extent of corrosion is divided into three grades, what the corrosion part was short and shallow rots for the I level, and long and shallow rots for the II level, and long and dark rots for the III level, and three grades degree progression is respectively 1,2,3.The sum of products of the corrosion location in various degree of every rat and its degree progression as the extent of corrosion index, be the results are shown in Table 5.
Table 1 gastric mucosa extent of corrosion
| Group | 1 | 2 | 3 | 4 | 5 | 6 | X±SD |
| Matched group microsphere saponins group | 0 0 12 | 0 0 10 | 0 0 14 | 0 0 14 | 0 0 10 | 0 0 9 | 0 0 11.5±2.2 |
Anatomical lens is observed and is shown, matched group, microsphere group gastric mucosa pinkiness, and saponin group gastric mucosa is obvious dull gray yellow, and extent of corrosion is much larger than microsphere group (P＜0.05).
Pathological section shows, microsphere group gastric mucosa does not have significant change, saponin group gastric mucosa of rat has stronger stimulation, mucosa down and go to a grassroots level obvious congestion and edema and a large amount of inflammatory cell (lymphocyte, plasma cell, bite quick cell) of mucosa soak into, see Fig. 1, Fig. 2, Fig. 3.
Experimental result shows that the ophiopogonin enteric-coated microsphere can reduce the gastric mucosa zest.
2. release experiment in the acid
With reference to Chinese Pharmacopoeia drug release determination method first method, be dissolution medium with 0.1mol/L hydrochloric acid solution 250ml, temperature (37 ± 0.5 ℃), rotating speed 50r/min.Precision takes by weighing about 0.5g microsphere and puts in the cuvette, at regulation sample point draw solution 10ml, after centrifugal, supernatant all inclines to evaporating dish, water bath method, and residue is transferred in the tool plug test tube with dehydrated alcohol, after chromogenic reaction, measure absorption value and calculate burst size.Pressing in the acid of Chinese Pharmacopoeia enteric coated preparation release regulation release should be less than 10%.
Release test result (n=3) in table 2 acid
| Batch | Release in the acid (%) | RSD(％) |
| P1 P2 P3 | 8.3442±2.5001 8.6771±1.4927 8.2516±1.5279 | 2.66 |
Experimental result shows that ophiopogonin microsphere enteric coated preparation meets the pharmacopeia regulation, and release is less than 10% in the acid.
Conclusion: ophiopogonin enteric-coated microsphere preparation can reduce the gastric mucosa zest, realizes the targeted delivery of drugs of preparation.
Description of drawings:
Fig. 1, matched group Gastric Mucosal Cells tissue
Fig. 2, microsphere group Gastric Mucosal Cells tissue
Fig. 3, saponin group Gastric Mucosal Cells tissue
The specific embodiment:
Embodiment 1, the preparation of Radix Ophiopogonis total saponins extract
The material of getting it filled is a certain amount of, 10 times of 60% ethanol amount reflux, extract, 3 times, and each 1 hour, after extracting solution reclaimed ethanol, with 2000r/min centrifugal 10 minutes, the medicinal liquid standardize solution after centrifugal was to 0.9g crude drug/ml, as the upper prop test liquid.Adopt D101 resin purification ophiopogon root total saponin, sample concentration is 0.9g crude drug/ml on it, applied sample amount: 2.8g crude drug/g dried resin, begin with 0.1mol/l ammonia-50% ethanol as the eluant eluting behind the last sample absorption 1hr, ophiopogon root total saponin content can reach 70% in its eluate, to total Saponin enriched substance, the rate of transform reaches 62% from crude drug.
Embodiment 2,
Get acrylic resin II and pulverized 80 mesh sieves, with 85% dissolve with ethanol and be made into 3% concentration 300ml, standby.The Radix Ophiopogonis total saponins that embodiment 1 is made is dissolved in the capsule material solution than (g/g) by spice at 1: 3, add Oleum Ricini 5ml, after stirring, add micropowder silica gel 2.5g again, stir down, by 80 ℃ of inlet temperature, 60 ℃ of leaving air temps, nebulizer rotating speed 30RPM, the process conditions of charging rate 30ml/min are carried out spray drying, promptly.
Embodiment 3,
Get hydroxypropylmethyl cellulose phthalate, with 80% dissolve with ethanol and be made into 3% concentration 300ml, standby.The Radix Ophiopogonis total saponins that embodiment 1 is made is dissolved in the capsule material solution than (g/g) by spice at 1: 2, add Oleum Ricini 4ml, after stirring, add micropowder silica gel 3.5g again, stir down, by 90 ℃ of inlet temperature, 70 ℃ of leaving air temps, nebulizer rotating speed 40RPM, the process conditions of charging rate 40ml/min are carried out spray drying, promptly.
Embodiment 4, the preparation of microcapsule capsule
Get the microsphere 10g that embodiment 2 makes, starch, dextrin, calcium carbonate be 40g altogether, and principal agent and the abundant mix homogeneously of adjuvant is encapsulated, makes 100 altogether, every 0.5g, promptly.
Embodiment 5, microencapsule tablet preparation
Get the microsphere 10g that embodiment 3 makes, add microcrystalline Cellulose 38g, magnesium stearate 2g, abundant mix homogeneously, tabletting is made 100 altogether, every 0.5g, promptly.
Claims (4)
1, ophiopogonin enteric-coated microsphere preparation is characterized in that said preparation percentage by weight prescription consists of Radix Ophiopogonis total saponins extract 5-20%, high score ascus material 20-40%, antitackiness agent 20-40% and plasticizer 10-30%; Microspherulite diameter is 10-50 μ m;
Wherein the Radix Ophiopogonis total saponins extract is meant that ophiopogonin content that the ethanol extract of raw medicinal herbs Radix Ophiopogonis obtains is greater than 60% extract behind purification by macroporous resin;
High score ascus material is meant acrylic resin II or hydroxypropylmethyl cellulose phthalate; Antitackiness agent is meant micropowder silica gel or Pulvis Talci; Plasticizer is meant Oleum Ricini, glycerol or O-phthalic acid diacid ester.
2, the preparation method of ophiopogonin enteric-coated microsphere preparation according to claim 1 is characterized in that the preparation method of said preparation comprises the following steps:
Measure the capsule material with dissolution with solvents and be made into 2-4%w/v concentration by proportioning, the Radix Ophiopogonis total saponins extract is dissolved in the capsule material solution, add plasticizer, stir, add antitackiness agent again, under agitation carry out spray drying, promptly get the microsphere that particle diameter is 10-50u m, according to dosage require directly to be filled into to make tablet after the glue shell is made capsule or tabletting.
3, the preparation method of ophiopogonin enteric-coated microsphere preparation according to claim 2 is characterized in that wherein said solvent is meant 85-95% ethanol or methanol.
4, the preparation method of ophiopogonin enteric-coated microsphere preparation according to claim 2, the process conditions that it is characterized in that wherein said spray drying method are meant inlet temperature 70-90 ℃, leaving air temp 50-70 ℃, nebulizer rotating speed 30-50RPM, charging rate 10-30ml/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310109428 CN1255098C (en) | 2003-12-15 | 2003-12-15 | Ophiopogonin enteric coated microsphere preparation and preparing process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310109428 CN1255098C (en) | 2003-12-15 | 2003-12-15 | Ophiopogonin enteric coated microsphere preparation and preparing process thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1546007A CN1546007A (en) | 2004-11-17 |
| CN1255098C true CN1255098C (en) | 2006-05-10 |
Family
ID=34335189
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200310109428 Expired - Fee Related CN1255098C (en) | 2003-12-15 | 2003-12-15 | Ophiopogonin enteric coated microsphere preparation and preparing process thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1255098C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100382805C (en) * | 2006-01-11 | 2008-04-23 | 南京工业大学 | Azithromycin enteric casing microsphere and its preparing process |
| CN105223326B (en) * | 2015-09-23 | 2017-01-18 | 天津中医药大学 | In-vitro classification method for active constituents in traditional Chinese medicine oral fast release preparation |
-
2003
- 2003-12-15 CN CN 200310109428 patent/CN1255098C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1546007A (en) | 2004-11-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101775058B (en) | Preparation and application of pharmaceutical preparation of 11-carbonyl-betal- acetyl mastic acid and derivatives thereof extracted from frankincense | |
| CN1330670C (en) | Process for extracting polygonatum polysaccharides, preparing process for medical preparation and use thereof | |
| CN100534508C (en) | Method for extracting effective sites group of smilax China root | |
| CN114209739A (en) | Application of pulsatilla chinensis extract in preparation of antidepressant drug | |
| CN1939443A (en) | Preparation and use for loquat-leaf extract | |
| CN1255098C (en) | Ophiopogonin enteric coated microsphere preparation and preparing process thereof | |
| CN1861080A (en) | Use of phytolaccagenin in preparing medicine for treating azoplasia | |
| CN101332229A (en) | Prunella plant extract, preparation method and use thereof | |
| CN1733054A (en) | Dogwood fruit extract and its preparation process | |
| CN101040891B (en) | Method of preparing tripterygium hypoglaucum (Levl) hutch alkaloids | |
| CN102614258A (en) | Chinese medicinal composition with blood sugar reducing effect, and preparation method and application thereof | |
| CN1256120C (en) | Medicine for treating chronic pelvic inflammation and its preparing method | |
| CN1264533C (en) | Radix salvia miltiorrhiza capsule compound and method for preparing same | |
| CN112807337B (en) | Canbacha extract as well as preparation method and application thereof | |
| CN102552491B (en) | Dai-dai fruit total flavonoid self-microemulsion micro pill and preparation method thereof | |
| CN1861081A (en) | Use of phytolaccatoxin for preparing medicine to treat mazoplasia | |
| CN1709401A (en) | Chinese medicine slow-release formulation containing asiatic pennywort herb water-soluble active ingredient, and its preparing method | |
| CN103494894A (en) | Traditional Chinese medicine composition with effect of reducing blood sugar, as well as preparation method and application thereof | |
| CN113768896B (en) | Gardenia duodenum positioning preparation for treating cholestatic liver diseases | |
| CN1303981C (en) | Preparation method of Fuyankang medicine for treating gynecopathy | |
| CN116350736B (en) | Traditional Chinese medicine composition for preventing and treating breast nodules | |
| CN108864128A (en) | Four kinds of guassin industrial production process and its prepare drug, health food new application | |
| CN107669738B (en) | Traditional Chinese medicine preparation for promoting blood circulation to remove blood stasis, tonifying qi and strengthening heart and preparation method thereof | |
| CN106727384A (en) | A kind of tuber of dwarf lilyturf oligosaccharides sustained release tablets and preparation method thereof | |
| CN106421077A (en) | New preparing method of high purity shiny-leaved yellowhorn total saponins extractive 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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060510 Termination date: 20151215 |
|
| EXPY | Termination of patent right or utility model |