CN106138007A - The constituent of preparation enteric capsule shells, enteric capsule shells and preparation method - Google Patents
The constituent of preparation enteric capsule shells, enteric capsule shells and preparation method Download PDFInfo
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- CN106138007A CN106138007A CN201510168585.2A CN201510168585A CN106138007A CN 106138007 A CN106138007 A CN 106138007A CN 201510168585 A CN201510168585 A CN 201510168585A CN 106138007 A CN106138007 A CN 106138007A
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Abstract
The present invention provides a kind of constituent, enteric capsule shells and preparation method that can make enteric capsule shells, this constituent comprises: the water-soluble enteric solubility macromolecule of an energy, a water-soluble, film-forming macromolecule, an agglutinant and a flocculation aid, the water-soluble enteric solubility macromolecule of this energy comprises at least one hydrophobicity functional group and at least one hydrophilic functional group.The preparation method of this enteric capsule shells, its aforementioned component thing is dissolved in water after through heating and cool down with a capsule shells preparation liquid, soak pin and remove again after this capsule shells preparation liquid and dry a enteric capsule shells.The constituent that can make enteric capsule shells of the present invention can prepare an enteric capsule shells according to the preparation method of enteric capsule shells, it has excellent antiacid characteristic, and preparation process does not has organic solvent participate in, the problem that therefore can avoid organic solvent residual.
Description
Technical field
The present invention is with regard to a kind of constituent for preparing enteric capsule shells；The present invention is also with regard to a kind of intestines
Soluble gum softgel shell and preparation method thereof.
Background technology
In the middle of the field of oral drug, capsule is a kind of medicament aspect being extensively employed, and loads medicine
Medicine can be avoided in capsule directly to contact with gustatory organ causing nauseating reaction or being decomposed by saliva, and can make
Medicine and extraneous moisture content, air, light etc. are likely to result in medicine and become qualitative factor isolation, additionally also have
Delay the function of insoluble drug release.
General capsule be mainly composed of gelatin (gelatin), can dissolve in hydrochloric acid in gastric juice and discharge after its oral administration
Go out and be loaded in medicine therein；But, if some drugs will cause serious side effect in stomach release,
As nonsteroidal antiinflammatory drug (nonsteroidal anti-inflammatory drugs, NSAIDs) may cause stomach
The situations such as mucous membrane is impaired, gastrorrhagia or perforation occur.
In order to overcome the problems referred to above, a kind of enteric capsule shells of development on the market, it is it can be avoided that enteric solubility
The drug ingedient loading in capsule shells is released in the strong acid environment of stomach, and treats that this enteric capsule shells is moved
When moving to enteron aisle the environment of alkalescence relatively, the drug ingedient loading in this enteric capsule shells just can be released
And absorbed by enteron aisle, drug ingedient side effect produced by stomach can be reduced whereby.
And the preparation method of enteric capsule shells is divided into two kinds on the market, the first is not having antiacid characteristic
After general capsule preparation completes, then after this one layer of enteric film clothing of general capsule outer wrapping, form enteric solubility glue
Softgel shell, makes enteric capsule shells possess antiacid characteristic by this enteric film clothing, and this enteric film clothing
There is the solubility with pH-value change, it is however generally that, the composition of this enteric film clothing is acetic acid bran acid cellulose
(cellulose acetate phthalate, CAP), HPMCP
(hydroxypropyl methylcellulose phthalate, HPMCP), acetic acid esterified disuccinate
Cellulose-2-hydroxypropylmethyl ether (hydroxypropyl methylcellulose acetate succinate,
HPMP-AS), acrylic acid series copolymer (acrylic copolymers) or shellac (shellac).But, with this
The preparation method step that method prepares enteric capsule shells is complicated, and the composition of above-mentioned enteric film clothing is both needed to molten
In the middle of organic solvent, therefore the general capsule having loaded drug ingedient is after wrapping up this enteric film clothing, often
The situation having organic solvent residual occurs.
The method of another kind of preparation enteric capsule shells is secondary infusion method (double dipping method), its
It is to improve from the immersion forming process (dip molding process) used by general capsule preparation method thereof, wherein soak
Pin (pin) is dried after being sequentially immersed in a gelatin solution and an enteric film clothing solution and forms enteric capsulation
Shell, but because the composition of this enteric film clothing solution is identical with the composition of above-mentioned enteric film clothing, it still must be dissolved in
In the middle of organic solvent, therefore secondary infusion method still has the problem of organic solvent residual, and secondary infusion method is used
Equipment more typically to soak forming process expensive, also make production cost increase.Therefore, intestines on the market at present
Soluble gum softgel shell still has that preparation method step is complicated, preparation cost is expensive and the problem such as organic solvent residual needs gram
Clothes.
Content of the invention
It is an object of the invention to provide a kind of constituent for preparing enteric capsule shells, enteric solubility glue
Softgel shell and preparation method, to solve that prior art enteric capsule shells preparation method step is complicated, there are
The defect of machine dissolvent residual.
The present invention provides a kind of constituent for preparing enteric capsule shells, and it comprises:
One water miscible enteric solubility macromolecule, its molecular weight be 20,000 Doltons (kDa) to 1000kDa, should
Water miscible enteric solubility macromolecule can be soluble in water and to comprise at least one hydrophobicity functional group hydrophilic with at least one
Property functional group；
One water-soluble, film-forming macromolecule, which is gelatin (gelatin), poly-tri-glucose (pullulan), polyethylene
Alcohol (polyvinyl alcohol), modified starch (modified starch) and cellulose esters (cellulose ester)
In one or more, and its molecular weight is 50kDa to 815kDa；
One agglutinant, which is the blue glue (gellan gum) of knot or antler glue (carrageen), and its molecular weight is
450kDa to 550kDa；And
One flocculation aid (gelling aid)；
With this water miscible enteric solubility macromolecule, this water-soluble, film-forming macromolecule, this agglutinant and this flocculation aid
Gross weight be 100wt%, this high molecular percentage by weight of water miscible enteric solubility (weight percentage,
Wt%) being 5wt% to 25wt%, the high molecular percentage by weight of this water-soluble, film-forming is 71wt% to 94.45
Wt%, the percentage by weight of this agglutinant is 0.5wt% to 3wt%, and the percentage by weight of this flocculation aid is
0.005wt% to 1wt%.
This water miscible enteric solubility macromolecule possesses antiacid characteristic, and antiacid characteristic refers to this water miscible enteric solubility
Macromolecule under gastric acid environment in water-insoluble, then in water solubility in intestinal environment, specifically
It is that this water miscible enteric solubility macromolecule does not comprise gelatin, poly-tri-glucose, polyvinyl alcohol, modified shallow lake
Powder or cellulose esters.
This is used for preparing the constituent of enteric capsule shells as the follow-up starting material making enteric capsule shells,
And this composition being used for preparing the constituent of enteric capsule shells all can be dissolved in water, thus be accordingly used in preparation enteric solubility
It is not required to during capsule shells use organic solvent, therefore the problem that organic solvent residual can be avoided.
It is preferred that wherein this water miscible enteric solubility macromolecule is pectin (pectin), propylene glycol alginate
(propylene glycol alginate, PGA) or Xanthan gum (xanthan gum)；More preferably, this water solubility
Enteric solubility macromolecule be pectin or propylene glycol alginate；Again more preferably, this water miscible enteric solubility high score
Son is pectin.
It is preferred that this high molecular molecular weight of water miscible enteric solubility is 40kDa to 400kDa；More preferably
, this high molecular molecular weight of water miscible enteric solubility is 50kDa to 200kDa.
It is preferred that wherein this water miscible enteric solubility high molecular hydrophobicity functional group and hydrophilic functional group
Ratio be 30:70 to 70:30；More preferably, this water miscible enteric solubility high molecular hydrophobicity official
Can base be 40:60 to 60:40 with the ratio of hydrophilic functional group；Again more preferably, this water miscible intestines
The hydrophobicity functional group of soluble macromolecular and the ratio of hydrophilic functional group are 45:55 to 55:45.When dredge
When the ratio of aqueous functional group is less than 30%, by this for preparing prepared by the constituent of enteric capsule shells
Enteric capsule shells will excessively absorb water in aqueous and cause appearance deformation, and then may cause enteric solubility
The drug ingedient loading in capsule shells discharges in unexpected position because of deformation.
It is preferred that wherein this water miscible enteric solubility high molecular hydrophobicity functional group comprises methoxyl group
(methoxy group), propylene-glycol-based (propylene glycol) or a combination thereof；This water miscible enteric solubility is high
The hydrophilic functional group of molecule comprises carboxylic acid group (carboxyl group), amino (amino group) or a combination thereof.
More preferably, this water miscible enteric solubility high molecular hydrophobicity functional group comprises methoxyl group；This is water-soluble
The high molecular hydrophilic functional group of enteric solubility of property comprises carboxylic acid group.
It is preferred that wherein modified starch comprises hydroxypropyl starch (hydroxypropylated starch)
Or hydroxyethyl starch (hydroxyethylated starch).
It is preferred that wherein cellulose esters comprises hydroxypropyl methyl cellulose (hydroxypropyl
Methylcellulose, HPMC), hydroxypropyl cellulose (hydroxypropyl cellulose), methylcellulose
(methylcellulose), hydroxyethyl cellulose (hydroxyethyl cellulose) or HEMC
(hydroxyethyl methylcellulose)。
It is preferred that the high molecular molecular weight of this water-soluble, film-forming is 50kDa to 400kDa.
It is preferred that wherein this flocculation aid is monovalent cation salt, divalent cation salt or Tricationic salt；
More preferably, this flocculation aid is monovalent cation salt, makes this exist for the constituent preparing enteric capsule shells
Can high temperature (such as 70 DEG C to 90 DEG C) be dried to accelerate preparation process during preparation enteric capsule shells
Speed, without producing the phenomenon of enteric capsule shells embrittlement.
More preferably, monovalent cation salt is potassium chloride (potassium chloride, KCl) or sodium chloride
(sodium chloride, NaCl)；Divalent cation salt is calcium chloride (calcium chloride, CaCl2) or chlorine
Change magnesium (magnesium chloride, MgCl2)。
The present invention also provides the preparation method of a kind of enteric capsule shells, and it comprises:
Mixing is as previously described for preparing constituent and the water of enteric capsule shells, to obtain a capsule shells mixing
Liquid；
Heating cools down this capsule shells mixed liquor, again to obtain a capsule shells preparation liquid；
Soak pin in this capsule shells preparation liquid, and pin will be soaked move from this capsule shells preparation liquid
Go out, to obtain an immersion pin speckling with glue；And
It is dried this immersion pin speckling with glue, to obtain this enteric capsule shells on this immersion pin.
Cool down this capsule shells mixed liquor it is preferred that wherein heat again, to obtain this capsule shells preparation liquid
Step includes:
Heat the temperature of this capsule shells mixed liquor between 65 DEG C to 90 DEG C；
Cool down this capsule shells mixed liquor, to obtain this capsule shells preparation liquid.
More preferably, the temperature of this capsule shells mixed liquor is heated between 75 DEG C to 85 DEG C.
It is preferred that be wherein dried this immersion pin speckling with glue, to obtain this enteric solubility on this immersion pin
The step of capsule shells includes:
Be dried this speckle with glue immersion pin temperature between 20 DEG C to 90 DEG C, to obtain on this immersion pin
This enteric capsule shells.
More preferably, it is dried the temperature of this immersion pin speckling with glue between 20 DEG C to 80 DEG C；Again more preferably
It is to be dried the temperature of this immersion pin speckling with glue between 20 DEG C to 70 DEG C.
More preferably, it is dried the temperature of this immersion pin speckling with glue between 70 DEG C to 80 DEG C.
Cool down this capsule shells mixed liquor it is preferred that wherein heat again, to obtain this capsule shells preparation liquid
Step includes:
Heat this capsule shells mixed liquor；
Cool down the temperature of this capsule shells mixed liquor between 50 DEG C to 60 DEG C, to obtain this capsule shells preparation liquid.
It is preferred that the temperature of this capsule shells preparation liquid need to maintain between 50 DEG C to 60 DEG C.
It is preferred that the pH-value of this capsule shells preparation liquid is pH 4 to pH 6.
The present invention also provides a kind of enteric capsule shells, and it comprises:
One water miscible enteric solubility macromolecule, its molecular weight is 20kDa to 1000kDa, and this is water miscible
Enteric solubility macromolecule energy is soluble in water and comprises at least one hydrophobicity functional group and at least one hydrophilic functional group；
One water-soluble, film-forming macromolecule, which is gelatin, poly-tri-glucose, polyvinyl alcohol, modified starch and
One or more in cellulose esters, and its molecular weight is 50kDa to 815kDa；
One agglutinant, which is the blue glue of knot or antler glue, and its molecular weight is 450kDa to 550kDa；
And
Water (moisture)；
Gross weight with this enteric capsule shells is 100%, this high molecular weight percent of water miscible enteric solubility
Ratio is 5wt% to 25wt%, and the high molecular percentage by weight of this water-soluble, film-forming is 65wt% to 90.5
Wt%, the percentage by weight of this agglutinant is 0.5wt% to 3wt%, and the percentage by weight of water is 4wt%
To 7wt%.
It is preferred that wherein this water miscible enteric solubility macromolecule is pectin, propylene glycol alginate or Xanthan gum；
More preferably, this water miscible enteric solubility macromolecule is pectin or propylene glycol alginate；Again more preferably, should
Water miscible enteric solubility macromolecule is pectin.
It is preferred that this high molecular molecular weight of water miscible enteric solubility is 40kDa to 400kDa；More
Good, this high molecular molecular weight of water miscible enteric solubility is 50kDa to 200kDa.
It is preferred that wherein this water miscible enteric solubility high molecular hydrophobicity functional group and hydrophily official's energy
The ratio of base is 30:70 to 70:30；More preferably, this high molecular hydrophobicity of water miscible enteric solubility
Functional group is 40:60 to 60:40 with the ratio of hydrophilic functional group；Again more preferably, this is water miscible
Enteric solubility high molecular hydrophobicity functional group is 45:55 to 55:45 with the ratio of hydrophilic functional group.
It is preferred that wherein this water miscible enteric solubility high molecular hydrophobicity functional group comprise methoxyl group,
Propylene-glycol-based or a combination thereof；The high molecular hydrophilic functional group of this water miscible enteric solubility comprises carboxylic acid group, ammonia
Base or a combination thereof.
More preferably, this water miscible enteric solubility high molecular hydrophobicity functional group comprises methoxyl group；This is water-soluble
The high molecular hydrophilic functional group of enteric solubility of property comprises carboxylic acid group.
It is preferred that wherein modified starch comprises hydroxypropyl starch or hydroxyethyl starch.
It is preferred that wherein cellulose esters comprises hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl
Cellulose, hydroxyethyl cellulose or HEMC.
It is preferred that the high molecular molecular weight of this water-soluble, film-forming is 50kDa to 400kDa.
The constituent for preparing enteric capsule shells of the present invention, according to the enteric capsule shells of the present invention
Preparation method can prepare an enteric capsule shells, it has excellent antiacid characteristic, and antiacid characteristic refers to this
Water miscible enteric solubility macromolecule under gastric acid environment (about pH 1.2) in water-insoluble, and in intestinal environment
(about pH 6.8) is then in water solubility, and does not has the participation of organic solvent in preparation process completely, therefore permissible
The problem avoiding organic solvent residual.
Detailed description of the invention
Embodiment 1
The present embodiment provides the preparation method of a kind of enteric capsule shells, and it is used for preparing enteric capsulation by one
The constituent mixing of shell is dissolved in the deionized water (deionized water) of 6.1 kilograms (kilogram, kg), with
Obtain a capsule shells mixed liquor, by this capsule shells mixed liquor 80 DEG C of heating stirrings to after being completely dissolved, and
Being cooled to 55 DEG C and can obtaining a capsule shells preparation liquid, wherein, the pH-value of this capsule shells preparation liquid is pH 4.5.
This constituent being used for preparing enteric capsule shells comprises a water miscible enteric solubility macromolecule, water-soluble
Property film-forming high molecular, an agglutinant and a flocculation aid, this water miscible enteric solubility macromolecule possesses antiacid characteristic,
Antiacid characteristic refer to this water miscible enteric solubility macromolecule under gastric acid environment (about pH 1.2) in water-insoluble, and
In intestinal environment, (about pH 6.8) is then in water solubility, and this water miscible enteric solubility macromolecule is pectin (molecular weight
For 40kDa to 400kDa), pectin comprises hydrophobicity functional group (methoxyl group) and hydrophilic functional group's (carboxylic
Acidic group), and the ratio of the hydrophobicity functional group of pectin and hydrophilic functional group is 30:70, the sense of pectin
The ratio of base according to American Pharmacopeia<33>(The United States Pharmacopeial Convention,
USP<33>) try to achieve；This water-soluble, film-forming macromolecule is hydroxypropyl methyl cellulose, and its molecular weight is about 80
kDa；This agglutinant is the blue glue of knot, and its molecular weight is about 500kDa；This flocculation aid is potassium chloride, and this can
The usage amount making each composition in the constituent (being called for short " constituent " in table 1) of enteric capsule shells is listed in table
1。
This capsule shells preparation liquid is poured into and is stained with in glue groove, and maintain the temperature of this capsule shells preparation liquid in 50 DEG C
To 55 DEG C, soak pin in this capsule shells preparation liquid, and pin will be soaked from this capsule shells preparation liquid
Middle removal, to obtain an immersion pin speckling with glue, being dried this immersion pin speckling with glue at 80 DEG C can
Obtaining a transparent enteric capsule shells, in this enteric capsule shells, the percentage by weight of each composition is listed in table 1.
Table 1: embodiment 1 to 4 and reference examples 1 to 3 for preparing in the constituent of enteric capsule shells
The percentage by weight of each composition in the usage amount of each composition and enteric capsule shells
Embodiment 2
The present embodiment provides the preparation method of a kind of enteric capsule shells, its enteric capsulation with embodiment 1
The preparation method of shell is roughly the same, and its difference is, this water-soluble, film-forming macromolecule is poly-tri-glucose
(pullulan), its molecular weight is about 805kDa.This is used for preparing in the constituent of enteric capsule shells and respectively becomes
The usage amount of part is listed in table 1, and in this enteric capsule shells, the percentage by weight of each composition is listed in table 1.
Embodiment 3
The present embodiment provides the preparation method of a kind of enteric capsule shells, its enteric capsulation with embodiment 1
The preparation method of shell is roughly the same, and its difference is, this water miscible enteric solubility macromolecule is alginic acid
Propane diols (propylene glycol alginate), its molecular weight is about 240kDa, and propylene glycol alginate has
Hydrophobicity functional group (propylene-glycol-based) and hydrophilic functional group (carboxylic acid group), and propylene glycol alginate is hydrophobic
Property functional group and hydrophilic functional group ratio be 35:65；This water-soluble, film-forming macromolecule is hydroxypropyl first
Base cellulose, its molecular weight is about 130kDa.This is used for preparing in the constituent of enteric capsule shells and respectively becomes
The usage amount of part is listed in table 1, and in this enteric capsule shells, the percentage by weight of each composition is listed in table 1.
Embodiment 4
The present embodiment provides the preparation method of a kind of enteric capsule shells, its enteric capsulation with embodiment 1
The preparation method of shell is roughly the same, and its difference is, this water miscible enteric solubility macromolecule is pectin,
The hydrophobicity functional group of pectin and the ratio of hydrophilic functional group are 40:60；And dry this is stained with at 30 DEG C
The immersion pin having glue can obtain this transparent enteric capsule shells.This is used for preparing the group of enteric capsule shells
The usage amount becoming each composition in thing is listed in table 1, and in this enteric capsule shells, the percentage by weight of each composition arranges
In table 1.
Reference examples 1
This reference examples provides the preparation method of a kind of enteric capsule shells, its enteric capsulation with embodiment 1
The preparation method of shell is roughly the same, and its difference is, this water miscible enteric solubility macromolecule is pectin,
The hydrophobicity functional group of pectin and the ratio of hydrophilic functional group are 28:72.This is used for preparing enteric solubility glue
In the constituent of softgel shell, the usage amount of each composition is listed in table 1, and the weight of each composition in this enteric capsule shells
Percentage is listed in table 1.
Reference examples 2
This reference examples provides the preparation method of a kind of enteric capsule shells, its enteric capsulation with embodiment 1
The preparation method of shell is roughly the same, and its difference is, this flocculation aid is calcium chloride, and this capsule shells mixes
Liquid heats stirring at 90 DEG C, and this immersion pin speckling with glue dry can obtain an enteric solubility glue at 70 DEG C
There is slight crack in the surface of softgel shell, only this enteric capsule shells.This is used for preparing the composition of enteric capsule shells
In thing, the usage amount of each composition is listed in table 1, and in this enteric capsule shells, the percentage by weight of each composition is listed in
Table 1.
Reference examples 3
This reference examples provides the preparation method of a kind of enteric capsule shells, its enteric solubility with embodiment 1
The preparation method of capsule shells is roughly the same, and its difference is, this water miscible enteric solubility macromolecule
For pectin, the hydrophobicity functional group of pectin and the ratio of hydrophilic functional group are 72:28.This is used for making
In the constituent of standby enteric capsule shells, the usage amount of each composition is listed in table 1, and in this enteric capsule shells
The percentage by weight of each composition is listed in table 1.
Test example
Respectively in the enteric capsule shells made by above-described embodiment 1 to 4 and reference examples 1 to 3
After filling acetamide phenol (acetaminophen, pressed powder), according to American Pharmacopeia<711>(The United
States Pharmacopeial Convention, USP<711>) carry out in vitro molten from test (in-vitro
dissolution test)。
In vitro the molten first stage from test is to be placed in enteric capsule shells in one simulation hydrochloric acid in gastric juice solution,
The pH-value of this simulation hydrochloric acid in gastric juice solution be pH the 1.2nd, temperature be 37 DEG C, treat that enteric capsule shells is placed in this
In simulation hydrochloric acid in gastric juice solution after 2 hours, measure and this simulation hydrochloric acid in gastric juice solution is filled thing (i.e. acetamide phenol)
Concentration, the concentration now recording is that the first stage is molten from test concentrations, molten from survey by the first stage
Examination concentration and this filler weight can try to achieve the acetamide phenol molten first stage from test in vitro
Molten from rate, its detailed computational methods refer to USP<711>.
In vitro molten from test second stage be connected in vitro molten from test first stage after carry out, its
The pH-value of this simulation hydrochloric acid in gastric juice solution is adjusted to pH 6.8 molten to obtain a simulation enteron aisle in five minutes
Liquid, this simulation enteron aisle solution is simulated intestinal environment, is treated that enteric capsule shells is placed in this simulation enteron aisle solution
In after 45 minutes, measure the concentration being filled thing in this simulation enteron aisle solution, the concentration now recording is
Second stage is molten from test concentrations, by second stage is molten can from test concentrations and this filler weight
Trying to achieve molten second stage molten from rate from test in vitro, its detailed computational methods refer to
USP<711>。
Enteric capsule shells made by embodiment 1 to 4 and reference examples 1 and 3 is molten from survey in vitro
The first stage of examination and the molten of second stage are listed in table 2 from rate.
Table 2: the enteric capsule shells made by embodiment 1 to 4 and reference examples 1 and 3 in vitro molten from
The first stage of test is molten from rate with second stage.
| Sample number into spectrum | First stage molten from rate (%) | Second stage molten from rate (%) |
| Embodiment 1 | 9.6 | 85.7 |
| Embodiment 2 | 9.5 | 84.5 |
| Embodiment 3 | 15.4 | 60.5 |
| Embodiment 4 | 5.9 | 87.7 |
| Reference examples 1 | 35 | 50 |
| Reference examples 3 | 38 | 80 |
Enteric capsule shells made by reference examples 1 molten first stage molten from rate from test in vitro
Up to 35%, and molten enteric solubility glue when test in vitro of the enteric capsule shells obtained by reference examples 1
The outward appearance gross distortion of softgel shell, this is hydrophobicity functional group and the parent of the pectin being used because of reference examples 1
The ratio of aqueous functional group is 28:72, when the ratio of hydrophilic functional group is too high, and made intestines
Soluble gum softgel shell easily excessively absorbs water and causes deformation so that being filled out of made enteric capsule shells
Fill thing to discharge in the case of unexpected；Review the enteric capsule shells made by embodiment 1 to 4 to exist
In vitro molten the molten of first stage from test is respectively less than 16%, and made enteric capsule shells from rate
Complete appearance, and the enteric capsule shells made by embodiment 1 to 4 in vitro molten from test when
Molten being all higher than 60% from rate, the enteric capsule shells representing made possesses excellent antiacid characteristic.
The molten in vitro first stage from test that enteric capsule shells made by reference examples 2 is not related to
It with the molten data from rate of second stage, is owing to when flocculation aid is calcium chloride, being dried at 70 DEG C
When this speckles with the immersion pin of glue, the enteric capsule shells being formed will occur embrittlement situation and cannot
Use, when therefore wanting to use calcium chloride or other divalent cation salt as flocculation aid, baking temperature
Need to set at least below 60 DEG C, so be dried required time increase by making, enteric solubility will be unfavorable for
The quick production of capsule shells；It in contrast to the enteric capsule shells made by embodiment 1 molten from survey in vitro
The molten of the first stage of examination is less than 10%, and the complete appearance of made enteric capsule shells from rate,
This explanation is the present invention can at high temperature be dried, beneficially the quick production of enteric capsule shells.
Enteric capsule shells made by reference examples 3 molten first stage molten from rate from test in vitro
Up to 38%, this is hydrophobicity functional group and the hydrophilic functional group of the pectin being used because of reference examples 3
Ratio be 72:28, when the ratio of hydrophobicity functional group is too high, made enteric capsule shells
In vitro molten from test when there is dissolution phenomena so that being filled of made enteric capsule shells
Thing discharges in the case of unexpected.
The foregoing is only the illustration of the explanation present invention, not do any pro forma restriction to the present invention,
The protection domain that the present invention is advocated should being as the criterion described in claim, rather than be only limitted to above-mentioned certainly
Embodiment.Those of ordinary skill in any art, without departing from technical solution of the present invention
In the range of, a little change or be modified to equivalent variations when the technology contents of available the disclosure above is made
Equivalent embodiments, as long as being the content without departing from technical scheme, according to the technology of the present invention
Above example is made any simple modification, equivalent variations and modification by essence, all still falls within skill of the present invention
In the range of art scheme.
Claims (20)
1. the constituent being used for preparing enteric capsule shells, it is characterised in that comprise:
One water miscible enteric solubility macromolecule, this water miscible enteric solubility molecular weight polymeric be 20kDa extremely
1000kDa, this water miscible enteric solubility macromolecule comprises at least one hydrophobicity functional group and at least one hydrophily
Functional group；
One water-soluble, film-forming macromolecule, this water-soluble, film-forming macromolecule is gelatin, poly-tri-glucose, polyethylene
One or more in alcohol, modified starch and cellulose esters, and this water-soluble, film-forming molecular weight polymeric is
50kDa to 815kDa；
One agglutinant, this agglutinant is the blue glue of knot or antler glue, and this agglutinant molecular weight is 450kDa
To 550kDa；And
One flocculation aid；
With this water miscible enteric solubility macromolecule, this water-soluble, film-forming macromolecule, this agglutinant and this flocculation aid
Gross weight be 100wt%, this high molecular percentage by weight of water miscible enteric solubility is 5wt% to 25wt%,
The high molecular percentage by weight of this water-soluble, film-forming is 71wt% to 94.45wt%, the weight of this agglutinant
Percentage is 0.5wt% to 3wt%, and the percentage by weight of this flocculation aid is 0.005wt% to 1wt%.
2. the constituent for preparing enteric capsule shells according to claim 1, it is characterised in that
The ratio of this water miscible enteric solubility high molecular hydrophobicity functional group and hydrophilic functional group be 30:70 extremely
70:30.
3. the constituent for preparing enteric capsule shells according to claim 2, it is characterised in that
The ratio of this water miscible enteric solubility high molecular hydrophobicity functional group and hydrophilic functional group be 40:60 extremely
60:40.
4. the constituent for preparing enteric capsule shells according to claim 3, it is characterised in that
The ratio of this water miscible enteric solubility high molecular hydrophobicity functional group and hydrophilic functional group be 45:55 extremely
55:45.
5. the constituent for preparing enteric capsule shells according to any one of claim 1 to 4,
It is characterized in that, this water miscible enteric solubility high molecular hydrophobicity functional group comprises methoxyl group, propylene-glycol-based
Or a combination thereof；The high molecular hydrophilic functional group of this water miscible enteric solubility comprises carboxylic acid group, amino or its group
Close.
6. the constituent for preparing enteric capsule shells according to any one of claim 1 to 4,
It is characterized in that, this water miscible enteric solubility high molecular hydrophobicity functional group comprises methoxyl group；This water solubility
The high molecular hydrophilic functional group of enteric solubility comprise carboxylic acid group.
7. the constituent for preparing enteric capsule shells according to any one of claim 1 to 4,
It is characterized in that, this water miscible enteric solubility macromolecule is pectin, propylene glycol alginate or Xanthan gum.
8. the constituent for preparing enteric capsule shells according to claim 7, it is characterised in that
This water miscible enteric solubility macromolecule is pectin or propylene glycol alginate.
9. the constituent for preparing enteric capsule shells according to claim 8, it is characterised in that
This water miscible enteric solubility macromolecule is pectin.
10. the constituent for preparing enteric capsule shells according to any one of claim 1 to 4,
It is characterized in that, this flocculation aid is monovalent cation salt or divalent cation salt.
11. constituents for preparing enteric capsule shells according to claim 10, its feature exists
In this flocculation aid is monovalent cation salt.
12. constituents for preparing enteric capsule shells according to any one of claim 1 to 4,
It is characterized in that, this high molecular molecular weight of water miscible enteric solubility is 40kDa to 400kDa.
13. constituents for preparing enteric capsule shells according to claim 12, its feature exists
In this high molecular molecular weight of water miscible enteric solubility is 50kDa to 200kDa.
The preparation method of 14. 1 kinds of enteric capsule shells, it is characterised in that comprise:
Hybrid right require according to any one of 1 to 13 for prepare enteric capsule shells constituent and
Water, to obtain a capsule shells mixed liquor；
Heating cools down this capsule shells mixed liquor, again to obtain a capsule shells preparation liquid；
Soak pin in this capsule shells preparation liquid, and pin will be soaked move from this capsule shells preparation liquid
Go out, to obtain an immersion pin speckling with glue；And
It is dried this immersion pin speckling with glue, to obtain this enteric capsule shells on this immersion pin.
The preparation method of 15. enteric capsule shells according to claim 14, it is characterised in that add
Heat cools down this capsule shells mixed liquor again, and the step to obtain a capsule shells preparation liquid includes:
Heat the temperature of this capsule shells mixed liquor between 65 DEG C to 90 DEG C；
Cool down this capsule shells mixed liquor, to obtain this capsule shells preparation liquid.
The preparation method of 16. enteric capsule shells according to claim 14, it is characterised in that dry
Dry this speckles with the immersion pin of glue, and the step to obtain this enteric capsule shells on this immersion pin includes:
Be dried this speckle with glue immersion pin temperature between 20 DEG C to 90 DEG C, to obtain on this immersion pin
This enteric capsule shells.
17. 1 kinds of enteric capsule shells, it is characterised in that comprise:
One water miscible enteric solubility macromolecule, this high molecular molecular weight of water miscible enteric solubility is 20kDa
To 1000kDa, this water miscible enteric solubility macromolecule energy is soluble in water and comprises at least one hydrophobicity official's energy
Base and at least one hydrophilic functional group；
One water-soluble, film-forming macromolecule, this water-soluble, film-forming macromolecule is gelatin, poly-tri-glucose, polyethylene
One or more in alcohol, modified starch and cellulose esters, and this water-soluble, film-forming molecular weight polymeric is
50kDa to 815kDa；
One agglutinant, this agglutinant is the blue glue of knot or antler glue, and this agglutinant molecular weight is 450kDa
To 550kDa；And
Water；
Gross weight with this enteric capsule shells is 100%, this high molecular weight percent of water miscible enteric solubility
Ratio is 5wt% to 25wt%, and the high molecular percentage by weight of this water-soluble, film-forming is 65wt% to 90.5
Wt%, the percentage by weight of the blue glue of this knot is 0.5wt% to 3wt%, and the percentage by weight of water is 4wt%
To 7wt%.
18. enteric capsule shells according to claim 17, it is characterised in that this water miscible intestines
Soluble macromolecular is pectin, propylene glycol alginate or Xanthan gum.
19. enteric capsule shells according to claim 17, it is characterised in that this water miscible intestines
The hydrophobicity functional group of soluble macromolecular comprises methoxyl group, propylene-glycol-based or a combination thereof；This water miscible enteric
The high molecular hydrophilic functional group of property comprises carboxylic acid group, amino or a combination thereof.
20. enteric capsule shells according to claim 17, it is characterised in that this water miscible intestines
The hydrophobicity functional group of soluble macromolecular and the ratio of hydrophilic functional group are 30:70 to 70:30.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106667951A (en) * | 2016-11-29 | 2017-05-17 | 四川旭华制药有限公司 | Preparation method of intestine soluble capsule material |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1452481A (en) * | 2000-09-01 | 2003-10-29 | 沃纳-兰伯特有限责任公司 | Pectin film compositions |
| US20100113620A1 (en) * | 2007-03-29 | 2010-05-06 | Aston University | Enteric pharmaceutical capsules |
-
2015
- 2015-04-10 CN CN201510168585.2A patent/CN106138007A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1452481A (en) * | 2000-09-01 | 2003-10-29 | 沃纳-兰伯特有限责任公司 | Pectin film compositions |
| US20100113620A1 (en) * | 2007-03-29 | 2010-05-06 | Aston University | Enteric pharmaceutical capsules |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106667951A (en) * | 2016-11-29 | 2017-05-17 | 四川旭华制药有限公司 | Preparation method of intestine soluble capsule material |
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Application publication date: 20161123 |