CN110279760A - A kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet - Google Patents
A kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet Download PDFInfo
- Publication number
- CN110279760A CN110279760A CN201910379809.2A CN201910379809A CN110279760A CN 110279760 A CN110279760 A CN 110279760A CN 201910379809 A CN201910379809 A CN 201910379809A CN 110279760 A CN110279760 A CN 110279760A
- Authority
- CN
- China
- Prior art keywords
- capsule
- total alkaloid
- coptis chinensis
- chinensis total
- release
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
- A61K36/718—Coptis (goldthread)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
Abstract
Prepared coptis chinensis total alkaloid intragastric floating sustained-release tablet in the application, single unit medicine-releasing system and multiple-unit medicine-releasing system are combined, film controlling type slow-releasing microcapsule is made in recipe quantity 80% coptis chinensis total alkaloid and auxiliary material, in the auxiliary materials such as film controlling type slow-releasing microcapsule and other hydrophilic gel matrix materials and recipe quantity 20% coptis chinensis total alkaloid is pressed into gastric endocopy, make it in first 30 minutes of release drug, external drug and hydrophilic gel matrix material slow release and corrosion, this stage is only in recipe quantity 20% drug release, therefore the phenomenon that being not in burst release, after 30 minutes, after external drug and bulk erosion, release internal micro-capsule, internal micro-capsule controls release by the fenestra on surface, reach slow release effect, to solve in the prior art, single unit discharges system may There is burst drug release, multiple-unit discharges system and there is the problems such as individual release difference.
Description
Technical field
This application involves pharmaceutical field more particularly to a kind of preparation methods of coptis chinensis total alkaloid intragastric floating sustained-release tablet.
Background technique
Gastric ulcer is clinical common digestive tract ulcer disease, is that stomach lining defect reaches or penetrate bursting for muscularis mucosae
Ulcer lesion, upper abdomen rhythmicity pain are main clinical manifestation, and some patientss are asymptomatic, serious person or with bleeding, block, wear
Hole or even canceration.Currently, the drug of clinical treatment gastric ulcer is mainly Western medicine, by gastric acid secretion inhibiting, pylorus spiral is eradicated
The modes such as bacillus, protection gastric mucosa.With the application of efficient proton pump inhibitor and elimination helicobacter pylori triple therapy, although
Rapidly, gastric ulcer cure rate is improved for effect, but there are still drug side-effects that big, part antimicrobial is also easy to produce drug resistance, is recurred
The problems such as rate is high.However, traditional Chinese medicine has its unique advantage in terms of anti-gastric-ulcer research, hence it is evident that improve symptom, improves cure rate,
Reduce recurrence rate and Small side effects, more clinical practice meaning and development prospect.
The drug that traditional Chinese medicine lists at present in terms of anti-gastric-ulcer research has a Berberine Hydrochloride Tablets, but these general formulations
Preparation process is outmoded, and effective component absorption difference, bioavilability is low, and the residence time is short in stomach, in addition first close eliminates effect,
It is difficult to play its effect, needs secondary administration more than a day, affect the treatment.
Gastric floating slow-release system, which refers to, floats on drug on gastric juice, rests on its long-time in stomach, and slowly release
Effective component is put, achievees the effect that sustained release, improves bioavilability, gives full play to the pharmacological action of effective component.Stomach floats now
Floating slow-released system mainly has sustained release pellet in gastric endoscopy stomach function regulating, and the gastric endoscopy that is distinguished as of the two is
Single unit discharges drug, and pellet is multiple-unit release drug, and the drugloading rate of gastric endocopy is big, convenient to take, but because it is
Single unit discharges drug, it is possible that dosage is difficult to adjust situations such as burst drug release or incomplete release；And pellet is more
A possibility that unit discharges drug, and contact area is big, reduces individual difference and burst release, but the disadvantage is that drugloading rate is small.
Summary of the invention
This application provides a kind of preparation methods of coptis chinensis total alkaloid intragastric floating sustained-release tablet, to solve the prior art
In, single unit discharges drug, it is possible that burst drug release or release are not exclusively, dosage is difficult to situations such as adjusting, reduce because
Multiple-unit discharges that medicament contact area is big, and generate individual drug release difference and burst release a possibility that, make up that drugloading rate is small etc. to ask
Topic.
It is as follows that the application solves the technical solution that above-mentioned technical problem is taken:
A kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet, which comprises
The extraction of coptis chinensis total alkaloid；
80% coptis chinensis total alkaloid in recipe quantity is mixed into system with capsule material, flocculating agent, liquid medium and pH adjusting agent
For at micro-capsule capsule-core；
Using coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent to the micro-capsule capsule-core into
Row clothing film coating prepares film controlling type slow-releasing microcapsule；
By in the film controlling type slow-releasing microcapsule and recipe quantity 20% coptis chinensis total alkaloid and hydrogel matrix,
The mixing of the additives such as bleach activator and foaming agent mixes, tabletted, obtains coptis chinensis total alkaloid intragastric floating sustained-release tablet.
Optionally, the extraction of the coptis chinensis total alkaloid includes:
Coptis medicine materical crude slice is pulverized and sieved to can pass through -100 mesh of 20 mesh；
The coptis medicine materical crude slice that 20g crushed is weighed, 2-10 times of Extraction solvent is poured into, the Extraction solvent is water or 20%-
80% ethanol solution extracts 1-5 times at being 40-80 DEG C in temperature, extracting solution is merged, 20-100mL is concentrated into, in temperature
It is to be dried in vacuo, be spray-dried at 40-80 DEG C, being freeze-dried 3-24h, obtains coptis chinensis total alkaloid.
Optionally, 80% coptis chinensis total alkaloid by recipe quantity and capsule material, flocculating agent, liquid medium and pH tune
Section agent is prepared by mixing into micro-capsule capsule-core, and the capsule material includes gelatin, cellacefate, ethyl cellulose methylcellulose, hydroxyl
Third methylcellulose, carboxymethyl cellulose, chitosan, alginate, gelatin-gum arabic, chitin-alginic acid salt, glucan its
Middle one or more；
The flocculating agent includes Na2SO4、NaHPO2One or more of；
The liquid medium is water；
The pH adjusting agent includes dilute hydrochloric acid, spirit of vinegar, citric acid, sodium citrate one or more.
Optionally, 80% coptis chinensis total alkaloid by recipe quantity and capsule material, flocculating agent, liquid medium and pH tune
Section agent is prepared by mixing into micro-capsule capsule-core and includes:
Capsule material is mixed with liquid medium water, the coptis chinensis total alkaloid for crossing -200 mesh of 20 mesh is added thereto, suspension is made
Liquid or emulsion, heating add pH adjusting agent to adjust pH, and flocculating agent, which is added, must agglomerate capsule, are eventually adding dilution, the dilution
It is 2-7 times, the flocculating agent that temperature is 5-20 DEG C obtains sedimentation capsule；
Sedimentation capsule is cooled to 15 DEG C or less plus 2-7 times of formalin, pH to 6-10 is adjusted with NaOH solution, must solidify
Capsule is washed with water to formaldehydeless smell to get capsule-core, needs to stir always in the whole process；
Wherein, when capsule material is mixed with water, capsule material concentration is 2-15%, capsule material and drug ratios 1:1-1:8, heating temperature
30-80 DEG C, mixing speed 50-1000r/min, drugloading rate is greater than 45%, and encapsulation rate is greater than 80%.
Optionally, described to use coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent to described
Micro-capsule capsule-core carries out clothing film coating, prepares in film controlling type slow-releasing microcapsule, the coating material includes cellulose acetate, ethyl cellulose
One of element, ethylene-vinyl acetate copolymer, acrylic resin, silicone elastomer, crossslinked sodium alginate, acetic starch or
It is several；
The biomembrane binder includes carbopol, hydroxypropylcellulose, carmethose, hyaluronic acid, poly- Tianmen
One or more of aspartic acid, polyglutamic acid, polystyrolsulfon acid, Polyvinyl sulfate；
The pore-foaming agent includes polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, lauryl sodium sulfate, sucrose, cream
One or more of sugar, salt or water soluble film-forming material (hydroxypropyl methyl cellulose, hydroxypropyl cellulose)；
The antiplastering aid includes one or more of talcum powder, magnesium stearate, silica, titanium dioxide etc.；
The plasticizer includes that glycerol, propylene glycol, polyethylene glycol, triethyl citrate, single triacetin, two acetic acid are sweet
One or more of grease, triacetyl glycerine, diethyl phthalate；
The solvent is water or acetone.
Optionally, described to use coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent to described
Micro-capsule capsule-core carries out clothing film coating, and preparing film controlling type slow-releasing microcapsule includes:
By coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent, in relative humidity 50%-
80%, at a temperature of 5 DEG C -60 DEG C, compressed air pressure 2-8kg/cm2It is lower to set the micro-capsule capsule-core in coating pan, clothing film
Weight gain is about 5-25mg, and dressing microcapsule is set 30-70 DEG C of baking oven inside holding 8-48h, obtains film controlling type slow-releasing microcapsule.
Optionally, 20% coptis chinensis total alkaloid by the film controlling type slow-releasing microcapsule and recipe quantity, hydrophilic solidifying
The mixing of the additives such as glue skeleton, bleach activator and foaming agent mixes, tabletted, obtains coptis chinensis total alkaloid intragastric floating sustained-release
Piece, the hydrogel matrix include methylcellulose, hydroxypropylcellulose, hyetellose, carboxymethyl cellulose, polyvinyl pyrrole
One or more of alkanone, polyvinyl alcohol, alginate；
The bleach activator includes one or more of glycerin monostearate, hexadecanol, octadecyl alcolol, beeswax, stearic acid；
The foaming agent includes one or more of magnesium carbonate, sodium bicarbonate, citric acid.
Optionally, 20% coptis chinensis total alkaloid by the film controlling type slow-releasing microcapsule and recipe quantity, hydrophilic solidifying
Glue skeleton, bleach activator and foaming agent mixing mix, and tabletted, obtaining coptis chinensis total alkaloid intragastric floating sustained-release tablet includes:
By in recipe quantity 20% coptis chinensis total alkaloid and the additives such as hydrogel matrix, bleach activator and foaming agent mix
It closes uniformly, crosses 20-100 mesh, the film controlling type slow-releasing microcapsule is added, mix, it is tabletted, it obtains in coptis chinensis total alkaloid stomach
Floating slow-release tablet；
Wherein, tableting pressure 2-8kg/cm2, slice weight 0.2-1g.
The technical scheme provided by the application includes following advantageous effects:
This application provides a kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet, the progress coptis first is always given birth to
The extraction of alkaloids, secondly by 80% coptis chinensis total alkaloid and capsule material, flocculating agent, liquid medium and pH adjusting agent in recipe quantity
It is prepared by mixing into micro-capsule capsule-core, using coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent to micro-capsule
Capsule-core carries out clothing film coating, prepares film controlling type slow-releasing microcapsule, finally by 20% Huang in film controlling type slow-releasing microcapsule and recipe quantity
Even the mixing of the additives such as total alkaloid, hydrogel matrix, bleach activator and foaming agent mixes, tabletted, obtains the coptis and always gives birth to
Alkaloids intragastric floating sustained-release tablet.Prepared coptis chinensis total alkaloid intragastric floating sustained-release tablet, will float in single unit stomach in the application
Floating type sustained-release tablets release system is combined with multiple-unit film controlling type slow-releasing microcapsule medicine-releasing system, obtains a kind of mono- multiple-unit switching
Type intragastric floating sustained-release tablet combines single unit medicine-releasing system and multiple-unit medicine-releasing system, by 80% Huang in recipe quantity
Even film controlling type slow-releasing microcapsule is made in total alkaloid and auxiliary material, by film controlling type slow-releasing microcapsule and other hydrophilic gel framework materials and
20% coptis chinensis total alkaloid in additives and recipe quantity is pressed into gastric endocopy, makes it 30 before discharging drug
In minute, external drug and skeleton slow release and corrosion, this stage are only in recipe quantity 20% drug releases, therefore
The phenomenon that being not in burst release, after 30 minutes, after external skeletal corrosion, discharges internal micro-capsule capsule-core, internal micro-capsule is logical
The fenestra control release for crossing surface, reaches slow release effect, to solve in the prior art, single unit discharges drug, may
There is burst drug release or release not exclusively, dosage is difficult to situations such as adjusting, and reduces contact surface due to multiple-unit discharges drug
A possibility that product is big, individual drug release difference and burst release, compensates for the problems such as drugloading rate is small.
Detailed description of the invention
In order to illustrate more clearly of the technical solution of the application, letter will be made to attached drawing needed in the embodiment below
Singly introduce, it should be apparent that, for those of ordinary skills, without any creative labor,
It is also possible to obtain other drawings based on these drawings.
Fig. 1 is the In-vitro release curves of coptis chinensis total alkaloid gastric endoscopy provided by the embodiments of the present application；
Fig. 2 is coptis chinensis total alkaloid gastric floating slow-release chip architecture provided by the embodiments of the present application；
Fig. 3 is film controlling type slow-releasing microcapsule structure provided by the embodiments of the present application.
Appended drawing reference: 1- film controlling type slow-releasing microcapsule, 2- hydrogel matrix layer, 3- foaming agent and bleach activator layer, 4- biology
Adhesion layer, 5- small delivery aperture, 6- micro-capsule capsule-core, 7- coatings.
Specific embodiment
In order to make those skilled in the art more fully understand the technical solution in the application, implement below in conjunction with the application
The technical solution in application embodiment is clearly and completely described in attached drawing in example；Obviously, described embodiment is only
It is a part of the embodiment of the application, instead of all the embodiments.Based on the embodiment in the application, ordinary skill
The model of the application protection all should belong in personnel's every other embodiment obtained without making creative work
It encloses.
The coptis is the Ranunculaceae coptis (CoptischinensisFranch.), the triangle leaf coptis
The dry rhizome of (CoptisdeltoideaC.Y.Chenget Hsial.) or Yun Lian (CoptisteetaWall.), it is bitter in taste
It is cold, return heart, liver, spleen, stomach and large intestine channel.There are the effect of good heat-clearing and damp-drying drug and purging fire for removing toxin, especially clear dampness-heat in middle jiao
Wing abdomen sore caused by retardance and functional activity of QI being not smooth is full and vomits acid regurgitation, meanwhile, it is silly swollen to can treat poison.Studies have shown that in the coptis
Jamaicin can reduce lactic dehydrogenase (LDH) and malonaldehyde (MDA) content, increase superoxide dismutase (SOD) content, inhibit
Gastric acid secretion, it is inhibited to helicobacter pylori.Clinically, 60 patients are combined using ulcerlmin and jamaicin and is controlled
It treats, wherein ulcerlmin makes jamaicin attach to gastric epithelial tissue as carrier, increases jamaicin action time, to mention
High jamaicin plays its effect in the effective concentration of gastric mucosa part to the maximum extent, thus improve patient's cure rate and in vivo
Helicobacter pylori clearance rate.Coptis chinensis total alkaloid has protective effect to gastric mucosa damage that stress be caused, inhibits granulation group
Growth is knitted, specific immune function is weakened, plays the role of inhibiting helicobacter pylori, gastric acid secretion inhibiting prevents it to be attached to
Stomach wall, the formation of preventing gastric ulcer, and it can be substantially reduced pepsin activity, its infringement to gastric mucosa is reduced, to reach
To the effect of protection gastric mucosa.
Gastric floating slow-release system, which refers to, floats on drug on gastric juice, rests on its long-time in stomach, and slowly release
Effective component is put, achievees the effect that sustained release, improves bioavilability, gives full play to the pharmacological action of effective component.With common mouth
Formulation is compared, and gastric floating slow-release system has the advantages that the drug that (1) needs frequently to use to half-life short, and reduction is given
Medicine number improves the compliance of patient；(2) blood concentration peak valley phenomenon is reduced, keeps blood concentration steady, reduces toxic side effect；
(3) improve oral drugs in the absorption of gastrointestinal tract；(4) bioavilability is improved.
This application provides a kind of preparation methods of coptis chinensis total alkaloid intragastric floating sustained-release tablet, by single unit floating in stomach
Type sustained-release tablets release system is combined with 1 medicine-releasing system of multiple-unit film controlling type slow-releasing microcapsule, obtains a kind of mono- multiple-unit switch type
80% coptis chinensis total alkaloid in recipe quantity is made film controlling type slow-releasing microcapsule 1 with auxiliary material, will carry medicine by intragastric floating sustained-release tablet
20% coptis chinensis total alkaloid in micro-capsule and other hydrophilic gel matrix materials and additives and recipe quantity is pressed into stomach
Floating tablet makes it in release first 30 minutes of drug, and external drug and skeleton slow release and corrosion, this stage will not
The phenomenon that being released after 30 minutes, after external skeletal corrosion, discharges internal micro-capsule, and the micro-capsule inside tablet is not
It is same as common micro-capsule, the micro-capsule in the application inside tablet is film controlling type slow-releasing microcapsule 1, and pore is added in the material of micro-capsule
Agent influences drug release rate by the micropore on micro-capsule surface, drug is made to reach a kind of film controlling type micro-capsule of slow releasing function.This is released
Prescription method is similar to osmotic pump tablet, but is not necessarily to laser boring.
Film controlling type slow-releasing microcapsule 1 is made of micro-capsule capsule-core 6, peel material, pore-foaming agent etc., by the insoluble polymer of gastrointestinal tract
Such as bleach activator and chitosan, Bletilla glucomannan etc. is added as capsule film material in cellulose acetate, ethyl cellulose, acrylic resin
Bioadhesion type carrier attaches on stomach lining while floating on gastric juice so that micro-capsule density is less than gastric juice.In peel
The water-soluble substances such as pore-foaming agent such as polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, lauryl sodium sulfate are added in liquid,
By this peel liquid packet to get the micropore capsule carrier of medicine-carried on drug containing micro-capsule.Micro-capsule capsule-core 6 should have certain degree of hardness and very fast
Dissolution rate, control the rate of release of drug by microporous barrier completely.Pore when microporous barrier and gastro-intestinal Fluid contact, on film
Agent meets water dissolution or falls off, and forms the sightless micropore of countless naked eyes or bending trail in micro-capsule clothing film, has cyst membrane logical
Permeability.Liquid in gastrointestinal tract is entered in film by micropore, is dissolved the drug in micro-capsule capsule-core 6, is generated certain osmotic pressure, due to
There are concentration difference inside and outside film, the drug in micro-capsule capsule-core 6 will pass through fenestra to film external diffusion, and drug is to making in film after film external diffusion
Drops are permeated, moisture goes successively to dissolve drug in film again, so recycle repeatedly.Microcapsule membrane is not destroyed in gastrointestinal tract,
It is finally excluded in vitro by enteron aisle, therefore film controlling type slow-releasing microcapsule 1 is preferably selected in intragastric floating sustained-release novel form.
To be avoided in multiple-unit administration process completely, non-at the uniform velocity release or burst release caused by the difference that releases the drug because of individual are asked
Topic, by recipe quantity 20% coptis chinensis total alkaloid and hydrophilic gel matrix material hydroxypropyl methyl cellulose, carboxymethyl cellulose
Plain sodium, sodium alginate etc., bleach activator sodium bicarbonate, the sieving of the additives such as foaming agent, mixing are tabletted with medicine carrying microcapsule.
This microcapsule-type intragastric floating tablets passes through single unit medicine-releasing system, tablet external hydrophilic gel skeleton quilt 30 minutes before drug release
While gastric juice corrosion, by 20% dose slow release, after 30 minutes, bleach activator sodium bicarbonate and gastric juice contact generate gas
Bubble, ruptures the skeleton outside tablet, releases the film controlling type slow-releasing microcapsule 1 inside tablet, after releasing micro-capsule, the bone of micro-capsule
It while frame material swims in it on gastric juice, attaches on stomach lining, is switched to multiple-unit drug delivery system.
The preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet provided by the embodiments of the present application, comprising the following steps:
S1: the extraction of coptis chinensis total alkaloid.
The coptis medicine materical crude slice that 20g crushed is weighed, 10 times of 50% ethanol solution is poured into, extracts 5 at being 70 DEG C in temperature
It is secondary, extracting solution is merged, 80mL is concentrated into, is dried in vacuo for 24 hours at being 50 DEG C in temperature, obtains coptis chinensis total alkaloid.
S2: 80% coptis chinensis total alkaloid in recipe quantity is mixed with capsule material, flocculating agent, liquid medium and pH adjusting agent
It is prepared into micro-capsule capsule-core 6.
Capsule material is mixed with liquid medium, the coptis chinensis total alkaloid for crossing -200 mesh of 20 mesh is added thereto, suspension is made
Or emulsion, heating add pH adjusting agent to adjust the pH of solution, flocculating agent are added, cohesion capsule is made, be eventually adding 7 times of dilution
Sedimentation capsule is made in liquid, the flocculating agent that temperature is 10 DEG C；
Sedimentation capsule is cooled to 15 DEG C or less the formalins for being added 7 times, pH to 8 is adjusted with NaOH solution, solidification is made
Capsule is washed with water to formaldehydeless smell to get micro-capsule capsule-core 6, needs to stir always in the whole process；
Wherein, when capsule material is mixed with water, capsule material concentration is 10%, and capsule material and drug ratios are 1:6, heating temperature 70
DEG C, mixing speed 1000r/min, drugloading rate is greater than 45%, and encapsulation rate is greater than 80%.
S3: using coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent to the micro-capsule capsule-core
6 carry out clothing film coating, prepare film controlling type slow-releasing microcapsule 1.
The preparation of coating membrane:
Coating fluid prescription (micro-capsule for per unit containing 100mg)
Coating: being coated with air suspension packaging technique, and feed liquor rate is 20ml/min, is wrapped to each micro-capsule capsule-core 6
Clothing weight gain 15.6mg, it is 50% that dressing microcapsule, which is placed in relative humidity, in 50 DEG C of environment, stores 50h, then do in drying box
Dry 25h.
The preparation of film controlling type slow-releasing microcapsule 1:
Example 1:
Gelatin and water are mixed, stirring, it is 30g/L that gelatin concentration, which is made, and gelatin solution is added, suspension, the coptis is made
Total alkaloid and gelatin ratio are 1:4.5, are heated to 50 DEG C, adjust pH to 3.5 with spirit of vinegar, Na is added2SO4, Na2SO4With it is bright
Glue ratio 1:1, the temperature for adding 3 times is 15 DEG C of water, is cooled to 15 DEG C or less plus formalin, with NaOH solution adjusting pH to
8, solidification capsule is obtained, is washed with water to formaldehydeless smell and obtains film controlling type slow-releasing microcapsule 1, pilot process need to stir always.
Example 2:
Coptis chinensis total alkaloid is mixed with 25g/L gelatin and 25g/L gumwater, obtains suspension or oil-in-water type
(O/W) type emulsion.In 50 DEG C of addition 50g/L vinegar acid for adjusting pH to 4, cohesion capsule is formed.It is diluted with 1-3 times of 30 DEG C of water,
It reduces interfacial tension and obtains sedimentation capsule, formalin is added at 10 DEG C, with the NaOH tune pH to 9 of 200g/L, obtains solidification capsule, wash
To formaldehydeless smell, film controlling type slow-releasing microcapsule 1 is obtained.
S4: by the film controlling type slow-releasing microcapsule 1 and 20% coptis chinensis total alkaloid, the hydrophilic gel in remaining recipe quantity
Skeleton, bleach activator and foaming agent mixing mix, tabletted, obtain coptis chinensis total alkaloid intragastric floating sustained-release tablet.
Example 1:(presses every 0.5 slice weight, 50 calculating)
Auxiliary material and drug are weighed by percentage shared by component each in prescription, is crushed, 80 meshes are crossed, it is slow that film controlling type is added
The mixing of micro-capsule 1 is released, magnesium stearate is added after mixing, is mixed.Using single-punching tablet press, the method for dry method direct tablet compressing prepares piece
Agent adjusts instrument, makes its slice weight 0.5g, pressure 5kg/cm2, the tablet appearance being prepared is yellow.
Example 2 (presses every 0.5 slice weight, 100 calculating)
Auxiliary material and coptis chinensis total alkaloid are weighed by percentage shared by component each in prescription, is crushed, 80 meshes are crossed, is added
Micro-capsule mixing, is added magnesium stearate after mixing, mix.Using single-punching tablet press, the method for dry method direct tablet compressing prepares tablet,
Instrument is adjusted, its slice weight 0.5g, pressure 5kg/cm are made2, the tablet appearance being prepared is yellow.
According to the first method basket method in 2015 editions Pharmacopoeias of the People's Republic of China, four drug release determination methods, survey respectively
The vitro release of fixed 8 groups of tablets (every group 6).Dissolution medium is 0.1mol/L hydrochloric acid solution 900mL, and medium temperature is (37
± 0.5) DEG C, revolving speed 100r/min, 0.5,1,2,4,6,8,10 and 12h of sample time.5mL is taken every time, and immediately in phase
It answers and supplements the synthermal dissolution medium of 5mL phase in stripping rotor.By samples taken through 0.45um filtering with microporous membrane.In 348nm wave
Strong point measures absorbance.The concentration of drug under various time points is calculated by standard curve, calculates accumulative release rate, such as Fig. 1
The In-vitro release curves of coptis chinensis total alkaloid gastric endoscopy provided by the embodiments of the present application are shown, can be seen by figure
The coptis chinensis total alkaloid intragastric floating tablets that the embodiment of the present application is prepared out have good slow release effect.
Coptis chinensis total alkaloid gastric floating slow-release piece preparation method provided by the embodiments of the present application, it is total to the coptis obtained by it
Alkaloid intragastric floating tablets have also carried out the research specifically acted in vitro, are always divided into two stages, specific as follows:
First stage: the hydrogel matrix outside tablet contacts gastric juice, and water swelling makes entire tablet density be less than stomach
Liquid shows the state swum on gastric juice.30% drug of tablet is released from hydrogel matrix layer 2, and gastric juice is slow
Slow-motion enters foaming agent and bleach activator layer 3 inside tablet, and carbon dioxide is generated in conjunction with internal foaming agent sodium acid, hydrophilic solidifying
Glue casing play 2 ruptures, and the film controlling type slow-releasing microcapsule 1 inside tablet releases, this process time 30 minutes, drug release
30%.It is illustrated in figure 2 coptis chinensis total alkaloid gastric floating slow-release chip architecture provided by the embodiments of the present application, it is wherein empty inside tablet
White region is foaming agent and bleach activator, and outer layer is hydrogel matrix layer.
Second stage: the bio-adhesive layer 4 in 1 coatings 7 of film controlling type slow-releasing microcapsule attaches to micro-capsule on stomach lining, prolongs
Long micro-capsule residence time in stomach, so that its long-time be made to discharge.Pore-foaming agent contact gastric juice in coatings is dissoluted, and makes micro-capsule
Surface forms small delivery aperture 5, and in spongy, the drug in micro-capsule capsule-core 6 forms concentration by small delivery aperture 5 and external gastric juice
Difference is released by aperture, achievees the effect that sustained release.Entire microcapsule matrices are insoluble framework material, and drug release finishes
Afterwards, framework material is excreted by gastrointestinal tract.Fig. 3 is 1 structure of film controlling type slow-releasing microcapsule provided by the embodiments of the present application, specifically
Including bioadhesive layer 4, small delivery aperture 5, coatings 7 and micro-capsule capsule-core 6 containing drug.
Single unit is discharged drug in-stomach floating type by prepared coptis chinensis total alkaloid intragastric floating sustained-release tablet in the application
It is slow that sustained release tablets with multiple-unit release drug film controlling type slow-releasing microcapsule 1 combine to obtain a kind of mono- multiple-unit switch type floating in stomach
Release piece, single unit medicine-releasing system and multiple-unit medicine-releasing system combined, by 80% coptis chinensis total alkaloid of recipe quantity with it is auxiliary
Film controlling type slow-releasing microcapsule 1 is made in material, and film controlling type slow-releasing microcapsule 1 and the coptis of other erodible auxiliary materials and remaining 20% are always given birth to
Alkaloids are pressed into gastric endocopy, make it in release first 30 minutes of drug, external drug and skeleton slow release with it is molten
The phenomenon that erosion, this stage is not in burst release, after 30 minutes, after external skeletal corrosion, discharges internal micro-capsule, thus
Solves single unit release drug in the prior art, it is possible that dosage is difficult situations such as burst drug release or incomplete release
A possibility that with adjustment, multiple-unit discharges drug, and contact area is big, reduces individual difference and burst release, but the disadvantage is that drugloading rate
Small problem.
It should be noted that the terms "include", "comprise" or its any other variant are intended to the packet of nonexcludability
Contain, so that article or equipment including a series of elements not only include those elements, but also including not arranging clearly
Other element out, or further include for elements inherent to such a process, method, article, or device.Not more
In the case where limitation, the element that is limited by sentence "including a ...", it is not excluded that including process, the side of the element
There is also other identical elements in method, article or equipment.
The above is only the specific embodiment of the application, is made skilled artisans appreciate that or realizing this Shen
Please.Various modifications to these embodiments will be apparent to one skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the application.Therefore, the application
It is not intended to be limited to the embodiments shown herein, and is to fit to and the principles and novel features disclosed herein phase one
The widest scope of cause.
It should be understood that the application is not limited to the content for being described above and being shown in the accompanying drawings, and can
To carry out various modifications and change without departing from the scope.Scope of the present application is only limited by the accompanying claims.
Claims (8)
1. a kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet, which is characterized in that the described method includes:
The extraction of coptis chinensis total alkaloid；
80% coptis chinensis total alkaloid in recipe quantity is prepared by mixing into capsule material, flocculating agent, liquid medium and pH adjusting agent
Micro-capsule capsule-core；
Clothing is carried out to the micro-capsule capsule-core using coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent
Film coating prepares film controlling type slow-releasing microcapsule；
By the film controlling type slow-releasing microcapsule in remaining recipe quantity 20% coptis chinensis total alkaloid, hydrogel matrix, help
The mixing of the additives such as agent and foaming agent is floated to mix, it is tabletted, obtain coptis chinensis total alkaloid intragastric floating sustained-release tablet.
2. the preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet according to claim 1, which is characterized in that described
The extraction of coptis chinensis total alkaloid includes:
Coptis medicine materical crude slice is pulverized and sieved to can pass through -100 mesh of 20 mesh；
The coptis medicine materical crude slice that 20g crushed is weighed, 2-10 times of Extraction solvent is poured into, the Extraction solvent is water or 20%-80%
Ethanol solution, temperature be 40-80 DEG C at extracts 1-5 times, extracting solution is merged, 20-100mL is concentrated into, temperature be 40-
It is dried in vacuo, is spray-dried at 80 DEG C, freeze-drying 3-24h, obtaining coptis chinensis total alkaloid.
3. the preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet according to claim 1, which is characterized in that described
80% coptis chinensis total alkaloid in recipe quantity is prepared by mixing into micro-capsule with capsule material, flocculating agent, liquid medium and pH adjusting agent
In capsule-core, the capsule material includes gelatin, cellacefate, ethyl cellulose methylcellulose, hydroxypropyl methylcellulose, carboxylic first fiber
Element, chitosan, alginate, gelatin-gum arabic, chitin-alginic acid salt, glucan are one of or several；
The flocculating agent includes Na2SO4、NaHPO2One or more of；
The liquid medium is water；
The pH adjusting agent includes dilute hydrochloric acid, spirit of vinegar, citric acid, sodium citrate one or more.
4. the preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet according to claim 1, which is characterized in that described
80% coptis chinensis total alkaloid in recipe quantity is prepared by mixing into micro-capsule with capsule material, flocculating agent, liquid medium and pH adjusting agent
Capsule-core includes:
Capsule material is mixed with liquid medium water, by cross -200 mesh of 20 mesh coptis chinensis total alkaloid be added thereto be made suspension or
Emulsion, heating add pH adjusting agent to adjust pH, and flocculating agent, which is added, must agglomerate capsule, are eventually adding dilution, and the dilution is 2-
7 times, the flocculating agent that temperature is 5-20 DEG C obtains sedimentation capsule；
Sedimentation capsule is cooled to 15 DEG C or less plus 2-7 times of formalin, pH to 6-10 is adjusted with NaOH solution, obtains solidification capsule, use
Formaldehydeless smell is washed to get capsule-core, needs to stir always in the whole process；
Wherein, when capsule material is mixed with water, capsule material concentration is 2-15%, capsule material and drug ratios 1:1-1:8, heating temperature 30-80
DEG C, mixing speed 50-1000r/min, drugloading rate is greater than 45%, and encapsulation rate is greater than 80%.
5. the preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet according to claim 1, which is characterized in that described
Clothing film packet is carried out to the micro-capsule capsule-core using coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent
Clothing is prepared in film controlling type slow-releasing microcapsule, and the coating material includes that cellulose acetate, ethyl cellulose, ethene-vinyl acetate are total
One or more of polymers, acrylic resin, silicone elastomer, crossslinked sodium alginate, acetic starch；
The biomembrane binder includes carbopol, hydroxypropylcellulose, carmethose, hyaluronic acid, poly-aspartic
One or more of acid, polyglutamic acid, polystyrolsulfon acid, Polyvinyl sulfate；
The pore-foaming agent include polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, lauryl sodium sulfate, sucrose, lactose,
One or more of salt or water soluble film-forming material (hydroxypropyl methyl cellulose, hydroxypropyl cellulose)；
The antiplastering aid includes one or more of talcum powder, magnesium stearate, silica, titanium dioxide etc.；
The plasticizer includes glycerol, propylene glycol, polyethylene glycol, triethyl citrate, single triacetin, two triacetins
One or more of ester, triacetyl glycerine, diethyl phthalate；
The solvent is water or acetone.
6. the preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet according to claim 1, which is characterized in that described
Clothing film packet is carried out to the micro-capsule capsule-core using coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent
Clothing, preparing film controlling type slow-releasing microcapsule includes:
By coating material, biomembrane binder, pore-foaming agent, antiplastering aid, plasticizer and solvent, in relative humidity 50%-80%, 5
At a temperature of DEG C -60 DEG C, compressed air pressure 2-8kg/cm2Lower to set the micro-capsule capsule-core in coating pan, clothing film increases weight about
For 5-25mg, dressing microcapsule is set into 30-70 DEG C of baking oven inside holding 8-48h, obtains film controlling type slow-releasing microcapsule.
7. the preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet according to claim 1, which is characterized in that described
By in the film controlling type slow-releasing microcapsule and recipe quantity 20% coptis chinensis total alkaloid and hydrogel matrix, bleach activator and
The mixing of the additives such as foaming agent mixes, tabletted, obtains in coptis chinensis total alkaloid intragastric floating sustained-release tablet, the hydrophilic gel
Skeleton include methylcellulose, hydroxypropylcellulose, hyetellose, carboxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol,
One or more of alginate；
The bleach activator includes one or more of glycerin monostearate, hexadecanol, octadecyl alcolol, beeswax, stearic acid；
The foaming agent includes one or more of magnesium carbonate, sodium bicarbonate, citric acid.
8. the preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet according to claim 1, which is characterized in that described
By 20% coptis chinensis total alkaloid, hydrogel matrix, bleach activator and the foaming in the film controlling type slow-releasing microcapsule and recipe quantity
The mixing of the additives such as agent mixes, and tabletted, obtaining coptis chinensis total alkaloid intragastric floating sustained-release tablet includes:
By in recipe quantity 20% coptis chinensis total alkaloid and the additives such as hydrogel matrix, bleach activator and foaming agent mix it is equal
It is even, 20-100 mesh is crossed, the film controlling type slow-releasing microcapsule is added, is mixed, it is tabletted, obtain coptis chinensis total alkaloid floating in stomach
Sustained release tablets；
Wherein, tableting pressure 2-8kg/cm2, slice weight 0.2-1g.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910379809.2A CN110279760A (en) | 2019-05-08 | 2019-05-08 | A kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910379809.2A CN110279760A (en) | 2019-05-08 | 2019-05-08 | A kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110279760A true CN110279760A (en) | 2019-09-27 |
Family
ID=68002395
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910379809.2A Pending CN110279760A (en) | 2019-05-08 | 2019-05-08 | A kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110279760A (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101023977A (en) * | 2007-04-02 | 2007-08-29 | 惠州九惠药业有限公司 | Slow-released tablet floating in stomach for treating gastric disease |
| CN101095666A (en) * | 2007-08-14 | 2008-01-02 | 石家庄欧意药业有限公司 | Novel hydrochloric acid tramadol sustained-release tablet |
| CN101190288A (en) * | 2006-11-20 | 2008-06-04 | 天津药物研究院 | Sustained-release oral traditional Chinese medicine preparation for treating gastric ulcer and preparation method thereof |
| CN101536990A (en) * | 2008-03-18 | 2009-09-23 | 普尔药物科技开发（深圳）有限公司 | Colchicines gastric floating sustained-release tablet and method for preparing same |
| CN101721417A (en) * | 2009-12-21 | 2010-06-09 | 深圳海王药业有限公司 | Entogastric lingering floating slow-release tablet for treating malignant tumor of gastrointestinal tract |
| CN201524268U (en) * | 2009-11-04 | 2010-07-14 | 青岛汉河药业有限公司 | Extended release pills in micro-capsules |
| CN102151304A (en) * | 2011-01-25 | 2011-08-17 | 四川省中医药科学院 | Gastric stasis system of total alkaloids of coptis and evodia rutaecarpa as well as preparation method and application thereof |
| CN102309589A (en) * | 2011-09-16 | 2012-01-11 | 陕西科技大学 | Zuojin gastric-floating tablet and preparation method thereof |
-
2019
- 2019-05-08 CN CN201910379809.2A patent/CN110279760A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101190288A (en) * | 2006-11-20 | 2008-06-04 | 天津药物研究院 | Sustained-release oral traditional Chinese medicine preparation for treating gastric ulcer and preparation method thereof |
| CN101023977A (en) * | 2007-04-02 | 2007-08-29 | 惠州九惠药业有限公司 | Slow-released tablet floating in stomach for treating gastric disease |
| CN101095666A (en) * | 2007-08-14 | 2008-01-02 | 石家庄欧意药业有限公司 | Novel hydrochloric acid tramadol sustained-release tablet |
| CN101536990A (en) * | 2008-03-18 | 2009-09-23 | 普尔药物科技开发（深圳）有限公司 | Colchicines gastric floating sustained-release tablet and method for preparing same |
| CN201524268U (en) * | 2009-11-04 | 2010-07-14 | 青岛汉河药业有限公司 | Extended release pills in micro-capsules |
| CN101721417A (en) * | 2009-12-21 | 2010-06-09 | 深圳海王药业有限公司 | Entogastric lingering floating slow-release tablet for treating malignant tumor of gastrointestinal tract |
| CN102151304A (en) * | 2011-01-25 | 2011-08-17 | 四川省中医药科学院 | Gastric stasis system of total alkaloids of coptis and evodia rutaecarpa as well as preparation method and application thereof |
| CN102309589A (en) * | 2011-09-16 | 2012-01-11 | 陕西科技大学 | Zuojin gastric-floating tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 梅紫薇等: "黄连总生物碱胃内漂浮缓释片处方组成的研究", 《中国现代应用药学》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101987081B (en) | Controlled release preparation | |
| EP1138320B1 (en) | Floating forms containing drug, polyvinyl acetate and polyvinyl pyrrolidone, their use and preparation | |
| US6277412B1 (en) | Pellet-type formulation intended for treating the intestinal tract | |
| FI113336B (en) | Process for the preparation of tramadol salt containing drug with sustained release of active substance | |
| Gazzaniga et al. | Oral delayed-release system for colonic specific delivery | |
| EP1890682B1 (en) | Use of polymer mixtures for the production of coated pharmaceutical formulations and pharmaceutical formulation with mixed polymeric coating | |
| RU2315595C2 (en) | Composition for enteric coating of lectin-containing natural product | |
| RO121082B1 (en) | Pharmaceutical compositions coated with an enterosoluble coating layer | |
| JPH09505609A (en) | Controlled-release dosage form of azithromycin | |
| EP3687502B1 (en) | Solid simethicone particles and dosage form thereof | |
| CN1394598A (en) | Dosage form with crispness coating and soft kernel | |
| DE69119217T2 (en) | COMPOSITIONS FOR CONTROLLED RELEASE | |
| CN101006989A (en) | Slow release preparation of alginic sodium diester | |
| JP2001523719A (en) | Spheroids containing tiagabine, production method and pharmaceutical composition | |
| CN104814923B (en) | A kind of tamsulosin hydrochloride sustained release preparation and preparation method thereof and its application | |
| WO2020060426A1 (en) | An oral preparation containing sodium butyrate | |
| WO2009038340A1 (en) | Pharmaceutical composition of artemisia extract using gastro-retentive drug delivery system and its oral sustained release formulation | |
| CN101249081A (en) | Administer orally controlled release drug administration pharmaceutical tablet | |
| CN110279760A (en) | A kind of preparation method of coptis chinensis total alkaloid intragastric floating sustained-release tablet | |
| US20110091536A1 (en) | Compositions comprising euphorbia prostrata and process of preparation thereof | |
| DE19850445A1 (en) | Medicines for the topical treatment of inflammatory bowel disease | |
| US9358205B2 (en) | Modified starch derivative-based matrix for colon targeting | |
| JP6905972B2 (en) | Pharmaceutical composition particles, orally disintegrating preparation containing them, method for producing pharmaceutical composition particles | |
| WO2005049048A1 (en) | Fiber rich fraction of trigonella foenum-graecum and its use as a pharmaceutcal excipient | |
| CN1232386A (en) | Colonic delivery of weak acid drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190927 |