CN108159014A - A kind of enteric plant capsule - Google Patents
A kind of enteric plant capsule Download PDFInfo
- Publication number
- CN108159014A CN108159014A CN201810018018.2A CN201810018018A CN108159014A CN 108159014 A CN108159014 A CN 108159014A CN 201810018018 A CN201810018018 A CN 201810018018A CN 108159014 A CN108159014 A CN 108159014A
- Authority
- CN
- China
- Prior art keywords
- acid
- layer
- copolymer
- antiacid
- antiacid solution
- 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.)
- Withdrawn
Links
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of enteric plant capsules, it at least has one layer of base layer and one layer of antiacid solution layer, the base layer includes one or more in hypromellose or derivatives thereof, the antiacid solution layer is set to the inside of base layer, containing the first antiacid solution agent in the antiacid solution layer, the described first antiacid solution agent is polyester polymer.The enteric plant capsule of the present invention will not rupture in gastric juice because of the dissolving of capsule substrate layer, ensure that capsule 's content will not be lost in gastric juice and be contaminated or lose drug effect.Simultaneously as dissolving of the substrate layer in gastric juice so that capsule dissolves more rapid in enteron aisle, helps speed up the rate of release of drug, quick, is not suitable for the substance discharged gastric juice suitable for filling.
Description
Technical field
The present invention relates to capsule technique fields, and in particular to a kind of enteric plant capsule.
Background technology
Certain capsule 's contents, such as esomeprazole magnesium, Omeprazole, Lansoprazole, Rabeprazole, tenatoprazole, Chinese mugwort
Salad azoles, Disuprazole, it is unstable in acid medium, it easily and quickly decomposes, so as to lose its pharmic function, for such
Capsule 's content needs it to be discharged in enteron aisle.
Chinese patent CN105106168A discloses a kind of esomeprazole magnesium capsulae enterosolubilis, by esomeprazole magnesium enteric
Pellet is filled common gastric-dissolved capsule and is prepared, and esomeprazole magnesium drug is made not contact gastric juice, is discharged in enteron aisle.But angstrom
Suo Meila azoles magnesium microsphere and its preparation is complicated and esomeprazole magnesium is easily decomposed by oxygen or illumination in preparation process, makes angstrom
The utilization rate of Suo Meila azoles magnesium also makes required cost prepared by capsule while decline.
Chinese patent CN106265587A discloses a kind of enteric hollow capsule and preparation method thereof, and it includes capsule housings
And enteric coating, wherein enteric coating are wrapped in the surface of capsule housing, avoid capsule and are crushed in gastric juice, improve enteric
The stability of effect, substantially increases product quality.
Enteric layer is arranged on outside so that capsule does not dissolve under one's belt, and is only dissolved in enteron aisle.Although it rises in this way
The effect of enteric has been arrived, but since capsule shells have certain thickness, so can not quickly be dissolved in enteron aisle, make content
Can not quick release, extend administration time.
Invention content
The present invention is to solve convenient effective drug substance contents the asking in enteron aisle quick release that will act on enteron aisle
Topic, provides a kind of novel capsulae enterosolubilis.It at least has one layer of base layer and one layer of antiacid solution layer, and base layer includes hydroxypropyl first
One or more in base cellulose or the derivative of hypromellose, antiacid solution layer is set to the inside of base layer, and
Containing the first antiacid solution agent in antiacid solution layer, the described first antiacid solution agent is polyester polymer.
Wherein, substrate layer is the key component of capsule shells, is the basic framework of capsule, ensures that capsule has enough mechanics
Intensity.
When the inside refers to that Capsules include content, the side of drug is contacted.The outside refers to not connect
Touch the side of content.
The antiacid solution layer refers to be arranged on the protective layer of energy stomach juice-resistant corrosion on the inside of substrate layer, can protect capsule contents
Object is not polluted by hydrochloric acid in gastric juice and loses drug effect.Capsule is after stomach, base layer dissolving, and antiacid solution layer is undissolved；And antiacid solution layer exists
It is quick damaged in enteron aisle, so as to achieve the effect that the quick release content in enteron aisle in time.Its antiacid solution performance is resisted by first
Acidolysis agent provides.Relative to the prior art, since the antiacid solution layer of the present invention is set to the inside of base layer, in base layer in stomach
It is necessary to have certain intensity to protect content after middle dissolving, so the antiacid solution agent used in the prior art is not necessarily fitted
For the antiacid solution layer of the present invention.Inventor's discovery, acrylic polymer, polyester polymer, polyether-based polymers or hydroxyl
The derivative of third methylcellulose, especially polyester polymer are used in the antiacid solution of the present invention as the first antiacid solution agent
When in layer, it can play the role of insoluble, rapidly-soluble in enteron aisle in stomach and keep enough intensity under one's belt,
Play the good result of protection content.
Wherein, the acrylic polymer refers to by acrylic acid or derivatives thereof, main such as acrylate, methyl-prop
The high molecular polymer that the monomer polymerizations such as olefin(e) acid ester, acrylic acid amides obtain.Specific such as polyacrylic acid, gathers at polymethyl acrylate
Homopolymers such as ethyl acrylate, polyacrylamide, polymethylacrylic acid, polymethyl methacrylate etc. and its, acrylic acid-first
Base acrylic copolymer, Eudragit S100, methyl acrylate-acrylic acid methacrylate copolymers etc.
Copolymer and the mixture of these homopolymers and/or copolymer.Acrylic polymer further includes acrylic monomer with it
The copolymer of its monomer, such as the polymerization of the same polyalcohol of acrylic monomer, polyacid, hydroxycarboxylic acid, lactone, anhydride compound
It is forming or by the same polyesters of macromolecular of acrylic compounds, polyethers, polyethers macro molecules by chemically react obtain poly- third
Olefin(e) acid class-polyester based copolymer, polyacrylic-polyethers analog copolymer etc..The copolymer can be random copolymer, hand over
For one or more in various types of copolymers such as copolymer, block copolymer or graft copolymer.
Polyester polymer is to be obtained by polyacid, polyalcohol, hydroxycarboxylic acid or their derivative by dehydrating polycondensation
Main chain in the high molecular polymer containing ester bond.Specifically such as hydroxycarboxylic acids such as polyhydroxybutyrate, polyhydroxybutyrate valerate
The polymerization of the dicarboxylic acids such as polymer, the polymer of the lactones such as polylactic acid, polycaprolactone, poly butylene succinate and dihydric alcohol
The dicarboxylic acids such as object, poly- decanedioic acid glyceride and the polymer of trihydroxylic alcohol and dicarboxylic acids-dihydric alcohol-ternary alcohol copolymer
Or hydroxycarboxylic acid-dihydric alcohol-ternary alcohol copolymer etc..Polyester polymer also includes itself and acrylic polymer, polyethers
The copolymer of polymer.
Polyether-based polymers are containing the polymer and its copolymer that repeat ehter bond or mixture, specific such as poly- second in molecule
Glycol, polypropylene glycol, polyethylene glycol propylene glycol copolymers etc..Polyether-based polymers also include its with acrylic polymer,
The copolymer of polyester polymer.
The derivative of hypromellose is mainly including but not limited to phthalic acid hypromellose, 1,2,4-
Benzenetricarboxylic acid hypromellose or acetate succinate hypromellose etc. it is one or more.
Further, the described first antiacid solution agent be dicarboxylic acids-dihydric alcohol-ternary alcohol copolymer or hydroxycarboxylic acid-
It is one or more in dihydric alcohol-ternary alcohol copolymer.Wherein, dicarboxylic acids specifically including but not limited to ethanedioic acid, malonic acid,
It is one or more in succinic acid, glutaric acid or adipic acid.Dihydric alcohol is specifically including but not limited to ethylene glycol, propylene glycol, fourth two
It is one or more in alcohol or neopentyl glycol.Trihydroxylic alcohol is specifically including but not limited to glycerine, trimethylolpropane or three hydroxyl first
It is one or more in base ethane.
Further, the described first antiacid solution agent be lactic acid-decanedioic acid-glycerine copolymer, succinic acid-ethylene glycol-
One kind or more in glycerine copolymer, adipic acid-ethylene glycol-glycerine copolymer or 1- hydroxyacetic acids-ethylene glycol-glycerine
Kind.
Further, the described first antiacid solution agent be lactic acid-decanedioic acid-glycerine copolymer and succinic acid-ethylene glycol-
The mixture of glycerine copolymer, and lactic acid-decanedioic acid-glycerine copolymer and succinic acid-ethylene glycol-glycerine copolymer
Mass ratio is 8/2~6/4.Lactic acid-decanedioic acid-glycerine copolymer is conducive to improve the rigidity of antiacid solution layer, so as to make capsule
There is enough intensity in hydrochloric acid in gastric juice, cracky, capsule 's content not will not flow out, and avoid being polluted and being failed by hydrochloric acid in gastric juice.Fourth two
Acid-ethylene glycol-glycerine copolymer has the function of to improve capsule toughness and controls capsule rate of dissolution, and the two acts synergistically,
The comprehensive performances such as intensity and the rate of dissolution of capsule can be improved.
Preferably, in the first antiacid solution agent the number-average molecular weight of lactic acid-decanedioic acid-glycerine copolymer for 5000~
30000, the mechanical strength of antiacid solution layer can be further improved, especially rigidly.Preferably, lactic acid-decanedioic acid-glycerine is common
The number-average molecular weight of polymers is 10000~20000.The number of succinic acid-ethylene glycol-glycerine copolymer is equal in first antiacid solution agent
Molecular weight is 10000~40000, can further improve the mechanical strength of antiacid solution layer, especially toughness.Preferably, fourth two
The number-average molecular weight of acid-ethylene glycol-glycerine copolymer is 22000~35000.
Further, the first antiacid solution agent accounts for the 60~95% of antiacid solution layer quality.
When the mass percentage of the first antiacid solution agent in antiacid solution layer is less than 60%, antiacid solution layer resists hydrochloric acid in gastric juice
Property it is inadequate, hydrochloric acid in gastric juice may enter capsule, reacted with content, reduce its drug effect；When the first antiacid solution in antiacid solution layer
When the mass percentage of agent is more than 95%, the adhesive force between antiacid solution layer and base layer is insufficient, can also reduce capsule to stomach
The resistivity of liquid.Preferably, the first antiacid solution agent accounts for the 70~85% of antiacid solution layer quality.
Further, for the base layer also comprising the second antiacid solution agent, the described second antiacid solution agent is acrylic compounds
Polymer, polyester polymer, polyether-based polymers or hypromellose derivative in it is one or more, and second
Antiacid solution agent accounts for the 5~15% of base layer quality.Second antiacid solution agent can reduce rate of dissolution of the substrate layer in hydrochloric acid in gastric juice, into
One step improves the antiacid solution performance of capsule.When the second antiacid mass fraction for solving agent less than 5%, resists substrate layer in substrate layer
Acidity is promoted little；When the mass fraction of the second antiacid solution agent in substrate layer is more than 15%, meltage is too in hydrochloric acid in gastric juice for substrate layer
It is few, decomposition rate of the capsule in enteron aisle can be reduced, release and the soak time of content is increased, influences the effect of content
Effect.Preferably, the second antiacid solution agent accounts for the 8~12% of substrate layer quality.
Further, the described second antiacid solution agent be acrylic acid-methacrylic acid copolymer, methyl methacrylate-
Methacrylic acid copolymer, methyl acrylate-acrylic acid methacrylate copolymers, acrylic acid-methacrylic acid-polylactic acid graft copolymerization
Object, polyethylene glycol-polylactic acid-polylysine copolymer, polylactic acid, polycaprolactone, PLA-PEG copolymer, poly- second
Glycol-polycaprolactone co-polymer, polyethylene glycol propylene glycol copolymers, hydroxypropyl methylcellulose phthalate or hydroxypropyl
It is one or more in methyl cellulose succinate.
Preferably, the second antiacid solution agent includes polyethylene glycol-polycaprolactone copolymer and polylactic acid-polyglycol
The mixture of copolymer, and the mass ratio of the two is 8/2~6/4.Inventor find, polyethylene glycol-polycaprolactone copolymer and
The mixture of PLA-PEG copolymer has the acid-resisting of substrate layer synergistic effect, and in the range of the mass ratio, base
Material layer is stronger to the resistivity of hydrochloric acid in gastric juice, and capsule 's content is relatively low in the dissolution rate of hydrochloric acid in gastric juice, and higher in the dissolution rate of enteron aisle.
Further preferably, the number-average molecular weight of the polyethylene glycol-polycaprolactone copolymer is 10000~30000,
The mass percentage of middle polycaprolactone segment is 40~80%, the equal molecule of number of the PLA-PEG copolymer
It is 1000~20000 to measure, and wherein the mass percentage of polylactic acid chain segment is 10~60%.Inventor's discovery, polyethylene glycol
In caprolactone copolymer the mass percentage of polycaprolactone segment within the above range when, substrate layer is to the resistivity of hydrochloric acid in gastric juice
It is stronger；The substrate layer for meeting the PLA-PEG copolymer preparation of above-mentioned condition is more preferable to the resistivity of hydrochloric acid in gastric juice, can be more
Capsule 's content is protected not polluted by hydrochloric acid in gastric juice well.
Most preferably, the number-average molecular weight of the polyethylene glycol-polycaprolactone copolymer is 15000~25000, wherein
The mass percentage of polycaprolactone segment is 60~80%；The number-average molecular weight of PLA-PEG copolymer is 1000
~5000, the wherein mass percentage of polylactic acid chain segment is 40~60%.
Further, the quality of the antiacid solution layer accounts for the 5%~20% of capsulae enterosolubilis gross mass.Work as capsulae enterosolubilis
In, the mass percentage of antiacid solution layer is less than 5%, and capsulae enterosolubilis is inadequate to the resistivity of hydrochloric acid in gastric juice；The quality of antiacid solution layer
Percentage composition is more than 20%, and rate of dissolution of the capsulae enterosolubilis in enteron aisle reduces, and is unfavorable for release of the capsule 's content in enteron aisle
And absorption.Preferably, the quality of the antiacid solution layer accounts for the 10%~15% of capsulae enterosolubilis gross mass.
Further, the antiacid solution layer also spreading out comprising hypromellose, starch, Propiram or above-mentioned substance
It is one or more in biology.
Further, the antiacid solution layer also includes water.
The ability that enteric plant capsule discharges drug under one's belt, in enteron aisle can be evaluated by the following method：With reference to 2015
Year version《Chinese Pharmacopoeia》It records dissolution test method for four and tests the enteric plant capsule containing lactose content in artificial stomach
The lactose dissolution rate of different time points in liquid or simulated intestinal fluid.
Further, the enteric plant capsule equipped with lactose content, using simulated gastric fluid as dissolution medium, 30 minutes
When lactose content dissolution rate<5%；Simulated intestinal fluid is dissolution medium, the dissolution rate of lactose content at 30 minutes>90%.
Preferably, the enteric plant capsule equipped with lactose content, using simulated gastric fluid as dissolution medium, lactose content at 30 minutes
The dissolution rate of object<3%；Using simulated intestinal fluid as dissolution medium, the dissolution rate of lactose content at 30 minutes>95%.
Further, the enteric plant capsule equipped with lactose content, using simulated intestinal fluid as dissolution medium, 15 minutes
When lactose content dissolution rate>90%.Preferably, the enteric plant capsule equipped with lactose content, with artificial intestines
Liquid is dissolution medium, the dissolution rate of lactose content at 15 minutes>95%.
The present invention also provides a kind of capsules, contain the enteric plant capsule of the present invention.The capsule it is interior
The tolerant various drugs, health products, one or more in food of can including.Especially, including needing to be absorbed in enteron aisle
Various drugs, health products, one or more in food, such as：Esomeprazole, Omeprazole, Lansoprazole, Lei Beila
Azoles, tenatoprazole, esaprazole, Disuprazole etc..
The enteric plant capsule of the present invention, it is antiacid by setting one layer of antiacid solution layer in the inside of plant capsule substrate layer
It solves layer not dissolving in gastric juice and with certain intensity so that capsule will not be broken in gastric juice because capsule substrate layer dissolves
It splits, ensures that capsule 's content will not be lost in gastric juice and lose using effect.Simultaneously as dissolving of the substrate layer in gastric juice,
So that dissolving of the capsule in enteron aisle is rapider, the rate of release of drug is helped speed up, it is quick.
Further, by adding a certain amount of second antiacid solution agent in substrate layer, natural plant gum can further be reduced
Dissolubility of the capsule in gastric juice, increases the protective capability to capsule 's content, can be widely applied to filling and is not suitable in gastric juice
The content of release.
It should be appreciated that such as " having ", "comprising" and " comprising " term used herein are not precluded one or more
A other materials, ingredient, performance, state, the presence or addition of element or combination；" being more than ", " being less than " all do not include numerical value
Itself, " more than ", " following " all include numerical value in itself.
Specific embodiment
It is further illustrated the present invention below by the mode of embodiment, does not therefore limit the present invention to the embodiment
Among range.The techniques implemented on the basis of the foregoing are all within the scope of the present invention.For being familiar with this field
For personnel, other modification is easily implemented, therefore general general being limited without departing substantially from claim and equivalency range
Under thought, the present invention is not limited to specific details.
Test event and its test method of the present invention are as follows, unless otherwise instructed, each test all at 25 DEG C into
Row.
The mass percentage of antiacid solution layer：The enteric plant capsule sample of certain mass is immersed in 3h in 80 DEG C of water to take
After going out, after the water washing of room temperature, drying, the quality after reaction, the quality of as antiacid solution layer, with the matter of antiacid solution layer are weighed
Amount divided by the quality of enteric plant capsule sample are multiplied by with 100%, you can obtain the quality of enteric plant capsule moderate resistance acidolysis layer
Percentage composition.
Number-average molecular weight：It is measured with gel permeation chromatography (GPC).
Thickness：After sample is cut apart with a knife or scissors, thickness is measured with calibrator.
Capsule water content：By version in 2015《Chinese Pharmacopoeia》The hydroxypropyl starch hollow capsule loss on drying of four records
Measuring method is measured.
Dissolution rate test：With reference to version in 2015《Chinese Pharmacopoeia》Four dissolution rates and drug release determination method, will be equipped with 200mg
The 0# enteric plant capsules of lactose content are put into 800mL dissolution mediums (simulated gastric fluid or simulated intestinal fluid), and rotating speed is per minute
100 turns, after 15 or 30 minutes, then by version in 2015《Chinese Pharmacopoeia》Four lactose content measuring methods are tested in dissolution medium
Lactose total content X (mg).Lactose dissolution rate calculates as follows：
Dissolution rate=X/200 × 100%.Wherein, the concocting method of simulated gastric fluid：Dilute hydrochloric acid 16.4mL is taken, adds water about
800mL and pepsin 10g, after shaking up, be diluted with water into 1000mL to get.The concocting method of simulated intestinal fluid：I.e. phosphate delays
Fliud flushing (containing pancreatin) (pH=6.8).
<Hypromellose>
A1：The carefree production of South Korea, hydroxypropoxy content 8.3%, 8wt% solution viscosities are 113mPas；
A2：The carefree production of South Korea, hydroxypropoxy content 9.4%, 8wt% solution viscosities are 282mPas.
<First antiacid solution agent>
B1：Polycaprolactone, the production of Aldrich chemical reagents corporations, viscosity 2.2dL/g；
B2：Ethanedioic acid-ethylene glycol-glycerine copolymer, prepares by the following method：It is 2.5 by molar ratio:1:1 ethanedioic acid, second
Glycol and glycerine under nitrogen protection, in 160 DEG C of dehydrating polycondensation certain times, obtain water white transparency solid after cooling, measure
Number-average molecular weight is 5000；
B3：Lactic acid-decanedioic acid-glycerine copolymer, prepares by the following method：It is 1 by molar ratio:1:1 lactic acid, decanedioic acid and
Glycerine under nitrogen protection, in 160 DEG C of dehydrating polycondensation certain times, obtains water white transparency solid after cooling, measure number and divide equally
Son amount is 2000；
B4：Succinic acid-ethylene glycol-glycerine copolymer, prepares by the following method：It is 2.5 by molar ratio:1:1 succinic acid, second
Glycol and glycerine under nitrogen protection, in 160 DEG C of dehydrating polycondensation certain times, obtain water white transparency solid, measure after cooling
Number-average molecular weight is 30000；
B5：Lactic acid-decanedioic acid-glycerine copolymer, prepares by the following method：By equimolar succinic acid, ethylene glycol and the third three
Alcohol under nitrogen protection, in 160 DEG C of dehydrating polycondensation certain times, obtains water white transparency solid, measures number-average molecular weight after cooling
It is 15000；
B6：Succinic acid-ethylene glycol-glycerine copolymer, prepares by the following method：It is 2.5 by molar ratio:1:1 succinic acid, second
Glycol and glycerine under nitrogen protection, in 160 DEG C of dehydrating polycondensation certain times, obtain water white transparency solid, measure after cooling
Number-average molecular weight is 15000.
<Second antiacid solution agent>
C1：Polycaprolactone, the production of Aldrich chemical reagents corporations, viscosity 2.2dL/g；
C2：Polyethylene glycol-polycaprolactone copolymer, the production of Aldrich chemical reagents corporations, number-average molecular weight 18000 are gathered
The mass percentage of caprolactone segment is 72.2%；
C3：Polyethylene glycol-polycaprolactone copolymer, the production of Aldrich chemical reagents corporations, number-average molecular weight 10000 are gathered
The mass percentage of caprolactone segment is 50%；
C4：PLA-PEG copolymer, the production of Aldrich chemical reagents corporations, number-average molecular weight 12000 gather breast
The mass percentage of sour segment is 16.7%；
C5：PLA-PEG copolymer, the production of Aldrich chemical reagents corporations, number-average molecular weight 1750 gather breast
The mass percentage of sour segment is 57.1%；
C6：Hydroxypropyl methylcellulose phthalate, the carefree production of South Korea, phthalyl content 30%, average mark
Son amount is 50000.
Examples 1 to 24
According to raw material and formula shown in table 1~3, it is prepared as follows to obtain the plant capsulae enterosolubilis of the present invention：
1st, the antiacid solution layer component as shown in table 1~3 is mixed with water by proportioning, is heated to 80 DEG C and is uniformly mixed, make
Mass fraction into solute is 10%~30% aqueous solution, and is cooled to 35 DEG C；
2nd, the base material layer component as shown in table 1~3 is mixed with water by proportioning, is heated to 80 DEG C and is uniformly mixed, be made
Hypromellose mass fraction is 10%~30% aqueous solution, and is cooled to 35 DEG C；
3rd, 0# capsule dies are immersed in aqueous solution prepared by the 1st step, take out and be positioned over 60 DEG C of drying in oven,
Capsule die surface forms one layer of antiacid solution layer；By adjusting the mass fraction of the solute in the 1st step, antiacid solution layer is adjusted
Thickness；
4th, the mold that antiacid solution layer is contained on surface is immersed in aqueous solution prepared by second step, taking-up is placed in 60 DEG C
Drying in oven takes out cutting, body cap sleeve obtains plant hollow capsule finished product after closing.By adjusting the hydroxypropyl first in second step
Base cellulose mass fraction adjusts the overall thickness of capsule wall to 110 μm (± 5%), and the quality that antiacid solution layer is adjusted with this accounts for
The percentage of capsule gross mass.Finished product is 0# Capsules.
Table 1
Table 2："/" represents that number is the mass ratio of mixture each component in " () " without the substance.
Table 3：Number is the mass ratio of mixture each component in " () ".
Comparative example 1
1st, hypromellose A1 with water is mixed, is heated to 80 DEG C and is uniformly mixed, hydroxypropyl methylcellulose is made
Plain mass fraction is 10%~30% aqueous solution, and is cooled to 35 DEG C；
2nd, 0# capsule dies are immersed in hypromellose aqueous solution, takes out and be positioned in 60 DEG C of baking oven and dry
It is dry, take out cutting, body cap sleeve obtains plant hollow capsule finished product after closing.By adjusting the hypromellose in the 1st step
Mass fraction the overall thickness of capsule wall is adjusted to 110 μm (± 5%).Finished product is 0# Capsules, only contains substrate layer, no
Contain antiacid solution layer.
Comparative example 2~3
1st, the base material layer component as shown in table 4 is mixed by proportioning with water, is heated to 80 DEG C and is uniformly mixed that hydroxypropyl is made
Methylcellulose mass fraction is 10%~30% aqueous solution, and is cooled to 35 DEG C；
2nd, the antiacid solution layer component as shown in table 4 is mixed with water by proportioning, is heated to 80 DEG C and is uniformly mixed, be made
The mass fraction of solute is 10%~30% aqueous solution, and is cooled to 35 DEG C；
3rd, 0# capsule dies are immersed in aqueous solution prepared by the 1st step, taking-up is placed in 60 DEG C of drying in oven, glue
Capsule die surface forms one layer of substrate layer；By adjusting the mass fraction of the hypromellose in the 1st step, base material is adjusted
The thickness of layer；
4th, the mold that substrate layer is contained on surface is immersed in aqueous solution prepared by second step, takes out and be positioned over 60 DEG C
Drying in oven, base material layer surface formed one layer of antiacid solution layer, take out cutting, body cap sleeve close after obtain plant hollow capsule into
Product.By adjusting the mass fraction of the solute in second step, the overall thickness of capsule wall is adjusted to 110 μm (± 5%), with this
The quality for adjusting antiacid solution layer accounts for the percentage of capsule gross mass.Finished product is 0# capsules, containing substrate layer and is arranged on substrate layer
The antiacid solution layer in outside.
Table 4："/" is represented without the substance.
The performance of capsule is measured according to method provided by the invention, measurement result is as shown in table 5.
Table 5
The enteric plant capsule of the embodiment of the present invention is can be seen that 30 minutes in simulated gastric fluid from the data shown in table 4
When dissolution rate it is all relatively low, dissolution rate in simulated intestinal fluid at 30 minutes is more than 90%, and 15 minutes in simulated intestinal fluid
When dissolution rate it is also higher, can be widely used in filling be not suitable for the content discharged in gastric juice.Comparative example compared to the examples,
1 plant capsule is due to no antiacid solution layer, and the dissolution rate in gastric juice is high, it is impossible to as capsulae enterosolubilis.Comparative example 2~3
The enteric plant capsule of preparation, containing antiacid solution layer, antiacid solution layer is in the outside of substrate layer, although the dissolution rate in gastric juice
Relatively low, still, the dissolution rate in enteron aisle is relatively low, and the dissolution rate particularly in simulated intestinal fluid at 15 minutes is significantly less than
Enteric plant capsule of the present invention, can not quickly be dissolved in enteron aisle, make content can not quick release, when extending administration
Between.
The composition and preparation method of enteric plant capsule described in above-described embodiment and be only some examples, can also
Enteric plant capsule of the present invention is prepared using others composition or method.
Claims (10)
1. a kind of enteric plant capsule, which is characterized in that at least with one layer of base layer and one layer of antiacid solution layer, the matrix
One or more in derivative of the layer comprising hypromellose or hypromellose, described antiacid solution layer settings
Containing the first antiacid solution agent in the inside of base layer, the antiacid solution layer, the described first antiacid solution agent is that polyester is birdsed of the same feather flock together
Close object.
2. enteric plant capsule according to claim 1, which is characterized in that the first antiacid solution agent is binary carboxylic
It is one or more in acid-dihydric alcohol-ternary alcohol copolymer or hydroxycarboxylic acid-dihydric alcohol-ternary alcohol copolymer.
3. enteric plant capsule according to claim 2, which is characterized in that the first antiacid solution agent is lactic acid-last of the ten Heavenly stems
Diacid-glycerine copolymer, succinic acid-ethylene glycol-glycerine copolymer, adipic acid-ethylene glycol-glycerine copolymer or 1- hydroxyls
It is one or more in guanidine-acetic acid-ethylene glycol-glycerine.
4. enteric plant capsule according to claim 3, which is characterized in that the first antiacid solution agent is lactic acid-last of the ten Heavenly stems
The mixture of diacid-glycerine copolymer and succinic acid-ethylene glycol-glycerine copolymer, and lactic acid-decanedioic acid-glycerine is common
The mass ratio of polymers and succinic acid-ethylene glycol-glycerine copolymer is 8/2~6/4.
5. enteric plant capsule according to claim 1, which is characterized in that the first antiacid solution agent accounts for antiacid solution layer
The 60~95% of quality.
6. enteric plant capsule according to claim 1, which is characterized in that the base layer also includes the second antiacid solution
Agent, the described second antiacid solution agent is acrylic polymer, polyester polymer, polyether-based polymers or hydroxypropyl methylcellulose
It is one or more in the derivative of element, and the second antiacid solution agent accounts for the 5~15% of base layer quality.
7. enteric plant capsule according to claim 6, which is characterized in that described second antiacid solution agent be acrylic acid-
Methacrylic acid copolymer, Eudragit S100, methyl acrylate-acrylic acid methacrylate copolymers,
Acrylic acid-methacrylic acid-polylactic acid graft copolymer, polylactic acid, gathers oneself at polyethylene glycol-polylactic acid-polylysine copolymer
Lactone, PLA-PEG copolymer, polyethylene glycol propylene glycol copolymers, hydroxypropyl methylcellulose phthalate
It is or one or more in hypromellose succinate.
8. enteric plant capsule according to claim 1, which is characterized in that the quality of the antiacid solution layer accounts for enteric glue
The 5%~20% of capsule gross mass.
9. according to claim 1~8 any one of them enteric plant capsule, which is characterized in that the institute equipped with lactose content
Enteric plant capsule is stated, using simulated gastric fluid as dissolution medium, the dissolution rate of lactose at 30 minutes<5%；Using simulated intestinal fluid as release
Medium, the dissolution rate of lactose at 30 minutes>90%.
10. enteric plant capsule according to claim 9, which is characterized in that the enteric equipped with lactose content is planted
Composite capsule, using simulated intestinal fluid as dissolution medium, the dissolution rate of lactose content at 15 minutes>90%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810018018.2A CN108159014A (en) | 2018-01-09 | 2018-01-09 | A kind of enteric plant capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810018018.2A CN108159014A (en) | 2018-01-09 | 2018-01-09 | A kind of enteric plant capsule |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108159014A true CN108159014A (en) | 2018-06-15 |
Family
ID=62517827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810018018.2A Withdrawn CN108159014A (en) | 2018-01-09 | 2018-01-09 | A kind of enteric plant capsule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108159014A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060165776A1 (en) * | 2005-08-31 | 2006-07-27 | Ramesh Sesha | Antidepressant oral pharmaceutical compositions |
| CN102119026A (en) * | 2008-06-13 | 2011-07-06 | 葛兰素集团有限公司 | Hydroxypropyl cellulose capsule shell |
| CN102552209A (en) * | 2012-01-06 | 2012-07-11 | 安徽黄山胶囊股份有限公司 | Double-layer hollow capsule and multi-layer enteric hollow capsule |
-
2018
- 2018-01-09 CN CN201810018018.2A patent/CN108159014A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060165776A1 (en) * | 2005-08-31 | 2006-07-27 | Ramesh Sesha | Antidepressant oral pharmaceutical compositions |
| CN102119026A (en) * | 2008-06-13 | 2011-07-06 | 葛兰素集团有限公司 | Hydroxypropyl cellulose capsule shell |
| CN102552209A (en) * | 2012-01-06 | 2012-07-11 | 安徽黄山胶囊股份有限公司 | Double-layer hollow capsule and multi-layer enteric hollow capsule |
Non-Patent Citations (1)
| Title |
|---|
| 王沛主编: "《药物制剂设备》", 31 January 2016, 中国医药科技出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102164600B1 (en) | Delayed release film coatings containing calcium silicate and substrates coated therewith | |
| KR101900505B1 (en) | High strength seamless alginate capsules | |
| KR101705204B1 (en) | Aqueous composition for hard capsule having enteric properties, method of preparing hard capsule having enteric properties and hard capsule prepared by the latter | |
| JP6272452B2 (en) | Film-forming composition for solid-state film coating | |
| CN1284533C (en) | Use of an acetylated pre-gelled starch with a high content of amylose | |
| EP2568973A2 (en) | Film coating composition and methods of making and using the same | |
| EP2229152A1 (en) | Water dispersible enteric coating formulation for nutraceutical and pharmaceutical dosage forms | |
| KR20110135876A (en) | Hard capsule | |
| WO2019013260A1 (en) | Enteric hard capsule | |
| CN107106501A (en) | The preparation of enteric film coated composition, method for coating and cladding | |
| JPS58172313A (en) | Enteric soft capsule | |
| TW200848094A (en) | Fast disintegration monolayer film for buccal administration of active substances | |
| JP5334727B2 (en) | Soft capsule manufacturing method | |
| WO2006121098A1 (en) | Soft capsule film composition | |
| CN108042506A (en) | A kind of enteric plant capsule and its capsule | |
| KR100483072B1 (en) | Film-forming composition suitable for hard capsules and method for preparing the same | |
| JP2000044465A (en) | Soft capsule agent | |
| Somwanshi et al. | Pharmaceutically used plasticizers: a review | |
| CN108159014A (en) | A kind of enteric plant capsule | |
| JP5705206B2 (en) | Hard capsule and method for producing the same | |
| WO2010093020A1 (en) | Hard capsule | |
| US20180303942A1 (en) | Polymer composition | |
| WO1997034932A2 (en) | Compositions containing starch excipients | |
| Patil et al. | Formulation and evaluation of matrix tablets containing chitosan based polyelectrolyte complex with natural gum for prolonged release of diltiazem HCl | |
| KR102427282B1 (en) | Enteric soft capsule composition having excellent oxidation stability and enteric soft capsule prepared from the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180615 |
|
| WW01 | Invention patent application withdrawn after publication |