CN109172618A - A kind of pulsatile capsules - Google Patents
A kind of pulsatile capsules Download PDFInfo
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- CN109172618A CN109172618A CN201811440335.XA CN201811440335A CN109172618A CN 109172618 A CN109172618 A CN 109172618A CN 201811440335 A CN201811440335 A CN 201811440335A CN 109172618 A CN109172618 A CN 109172618A
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- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
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Abstract
The invention belongs to pharmaceutical technology fields, provide a kind of Jinshuibao pulsatile capsules, are made of insoluble capsule body, initial bed, medicine layer, separation layer, block layer and soluble Capsule；Wherein, medicine layer is Paecilomyces hepiali chen Cs-4 fermentation cordyceps, positioned at the inside of insoluble capsule body；Initial bed is disintegrating agent, positioned at the bottommost of insoluble capsule body；Separation layer is between medicine layer and block layer；Block layer is to fit closely positioned at the open end of insoluble capsule body with insoluble capsule body inner wall with the matched circular piece of capsule mouth size, and concordant with the Nang Kou of insoluble capsule body.After soluble Capsule dissolution, block layer water swelling is detached from capsule, and the material dissolution in capsule body realizes delayed release.The present invention is prepared for the novel form of Jinshuibao product, and preparation method is simple, convenient to take, meets the needs of more crowds.
Description
Technical field
The invention belongs to pharmaceutical technology field more particularly to a kind of Jinshuibao pulsatile capsules.
Background technique
The effective component of Jinshuibao is fermentation cordyceps, specially Paecilomyces hepiali chen Cs-4 bacterium powder.The quasi- blueness of bat moth
Mould powder is isolated Cordyceps Militaris --- bat from fresh aweto (cordyceps sinensis (Berk) sacc)
Bat moth Paecilomyces varioti (Paecilomyces hepiali Chen&Dai) is made through liquid deep layer fermenting culture, filtering, drying, crushing
At product.
Peacilomyce hepiahi bacterium kind is Jiangxi Guoyao Co., Ltd and institute of Materia Medica,Chinese Academy of Medical Sciences health
Natural drug biosynthesis key lab of portion produces from Qinghai by 10 years and isolates and purifies and obtain in natural cordyceps, should
The fermentation cordyceps of strain production from the acquisitions Ministry of Public Health in 1989 are approved as a kind of bulk pharmaceutical chemicals new drug, and (code: it is quasi- that (89) defend medicine
Word Z-17), in the clinical application of more than ten years, good clinical effectiveness and reliable safety obtain domestic and international doctor deeply
The approval of medicine experts and scholars.
Clinically, Paecilomyces hepiali chen Cs-4 bacterium powder is made into a variety of dosage forms, forms the Jinshuibao product of series.But
There is not yet Jinshuibao to be made into the report of pulsatile capsules.Pulsed release refers to can be shifted to an earlier date according to the rhythm and pace of moving things of seizure of disease
Medication makes medication time and drug release time have a time difference to match with physiological period, facilitates medication.Jinshuibao product can
With the symptom for improving the diseases such as nephrosis, tuberculosis and chronic bronchitis, especially chronic bronchitis is easy in night-time attack,
Patient need to get up medication at night, or be easy to miss medication time, develop a kind of preparation right and wrong that can discharge drug at regular time and quantity
Often it is necessary to.
Summary of the invention
The purpose of the present invention is to provide a kind of Jinshuibao pulsatile capsules, and insoluble glue is prepared by improved method
Softgel shell prepares the block layer of special composition, and drug and soluble capsule cap are separated, while between medicine layer and block layer also
Containing separation layer, disintegrating agent is arranged at the bottom of insoluble capsule body, enables drug in the Jinshuibao pulsatile capsules being prepared
Enough time controlled releaseds, and the disintegration rate when starting release is fast, it is rapid-action.
Specifically, in view of the deficiencies of the prior art, the present invention provides the following technical scheme that
A kind of Jinshuibao pulsatile capsules, by insoluble capsule body, initial bed, medicine layer, separation layer, block layer and solubility
Capsule composition；Wherein, medicine layer is Paecilomyces hepiali chen Cs-4 fermentation cordyceps, positioned at the inside of insoluble capsule body；Bottom
The bed of material is located at the bottommost of insoluble capsule body；Separation layer is between medicine layer and block layer；Block layer is located at insoluble glue
The open end of utricule is fitted closely with insoluble capsule body inner wall, and concordant with the Nang Kou of insoluble capsule body.
Preferably, insoluble capsule body the preparation method comprises the following steps: (1) prepare ethyl cellulose solution；(2) by ethyl cellulose
In plain infusion to the capsule body of gelatin capsulae vacuus, redundant solution is struck off, keeps liquid level concordant with Nang Kou；(3) solvent is dried and removed,
Inner wall forms not soluble layer A, obtains the insoluble capsule body of inner wall；(4) the insoluble capsule body of inner wall is coated, is formed
Inner coating layer and exterior coating obtain the insoluble insoluble capsule body of inner and outer wall.
Preferably, the mass concentration of ethyl cellulose solution is 10-12%, and solvent is methylene chloride, anhydrous propanone and second
The mixed solvent that acetoacetic ester is mixed to get according to volume ratio 5:0.9-1.1:0.2-0.3.
Preferably, drying condition described in step (3) is 3-6 DEG C of temperature, drying time 50-70min；
The exterior coating of insoluble capsule body is in step (4) with a thickness of 5-10 μm, the overall thickness of inner coating layer and non-soluble layer A
It is 10-15 μm.
Preferably, coating method described in step (4) are as follows: prepare coating solution, control coating flow velocity 15-25l/h and into
It 45-55 DEG C of air temperature, is coated.
Preferably, the composition of coating solution are as follows: ethyl cellulose, dibutyl phthalate, magnesium stearate, glycerol, acetone
It is mixed to get according to 80-85g:10g:2-3g:1.5-1.8L:1.2-1.5L.
Preferably, the block layer is intumescent plunger, preparation method are as follows: takes the hydroxyethyl cellulose of recipe quantity and does
Starch, mixing, sieves with 100 mesh sieve, and the ethyl alcohol softwood of mass concentration 75% is added, and granulation, drying are crossed 20 mesh sieves, be added
Magnesium stearate, total mix, tabletting to get.
Preferably, the amount ratio of hydroxyethyl cellulose, dried starch, ethyl alcohol and magnesium stearate is 30-50g:15-20g:
2.5-4ml:2-3g；Wherein, hydroxyethyl cellulose can be replaced with hypromellose or sodium alginate.
Preferably, the weight ratio of initial bed, medicine layer, separation layer and block layer is 0.1-0.2:1:0.2-0.3:0.4-
0.6。
Preferably, initial bed is disintegrating agent, selected from sodium carboxymethyl starch, croscarmellose sodium, the poly- second dimension of crosslinking
One or both of ketone and low-substituted hydroxypropyl methylcellulose；
Separation layer is selected from one of sodium carboxymethyl starch, dried starch, cyclodextrin and glucose；
Soluble capsule cap is with insoluble capsule body with the capsule cap of the gelatine capsule shell of model.
Compared with prior art, it effect of the invention and has an advantage that:
1. insoluble capsule body is to form one layer of insoluble ethylcellulose on the inner wall of gelatine capsule by elder generation,
Then by coating, one layer of coatings are re-formed on softgel shell inner wall, form coatings on the outer wall；It obtains in this approach not
The hardness of dissolubility capsule body, good toughness, soluble layer is not uniform, and water or solution are impermeable into inside capsule shells.
2. the intumescent plunger of block layer is made of water swelling profile material, the wet granulation of technical maturity is specifically used
Method suppresses to obtain circular piece, i.e. plunger, and plunger is fitted closely with insoluble capsule body, by capsule capsule body material with it is solvable
Property capsule cap separate, only plunger water swelling, be detached from insoluble capsule body after, the material in capsule body could be molten from capsule
Out.
3. Jinshuibao pulsatile capsules provided by the invention, there are also separation layer between medicine layer and block layer, separation layer is
Water-soluble material, after the plunger of block layer is detached from insoluble capsule body, the material of separation layer is contacted with water or body fluid, is prolonged
Slow drug starts the time of release, realizes delayed release.
4. Jinshuibao pulsatile capsules provided by the invention have disintegrating agent in capsule shells underfill, so that drug is starting
Speed when release is fast, rapid-action, has the function that periodically, is quick-acting.
To sum up, after water-soluble capsule cap dissolution, the plunger exposure of block layer, water swelling, after the dissolution of capsule cap, plunger expansion
It is detached from insoluble capsule body, the drug release in medicine layer.Timed drug administrations may be implemented in pulsatile capsules, after medication 3-4 hours,
Drug starts to discharge, and generates drug effect；Drug user can according to need medication in advance, especially bedtime medication, improve sleep, reduce
The disease incidence of night cough, asthma, while also avoiding night and getting up the trouble of medication.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of Jinshuibao pulsatile capsules of the present invention.
Wherein, 1- initial bed；2- medicine layer；3- separation layer；4- block layer；5- solubility Capsule；The insoluble capsule body of 6-.
Specific embodiment
The present invention provides a kind of Jinshuibao pulsatile capsules, including insoluble capsule body, in insoluble capsule body from down toward
On be successively made of disintegrating agent initial bed, be made of Paecilomyces hepiali chen Cs-4 fermentation cordyceps medicine layer, by water
The separation layer and the block layer concordant with the open end of insoluble capsule body of soluble materials composition, block layer and insoluble capsule
Internal wall fits closely；Initial bed, medicine layer, separation layer and block layer weight ratio be 0.1-0.2:1:0.2-0.3:0.4-
0.6.After the intracorporal material of insoluble capsule is populated, the capsule cap with the utricule with the gelatine capsule shell of model is put on, is obtained
To Jinshuibao pulsatile capsules.
Wherein, insoluble capsule body the preparation method comprises the following steps:
(1) ethyl cellulose solution that mass concentration is 10-12% is prepared；Solvent is methylene chloride, anhydrous propanone and second
The mixed solvent that acetoacetic ester is mixed to get according to volume ratio 5:0.9-1.1:0.2-0.3.
(2) ethyl cellulose solution is filled into the capsule body of gelatin capsulae vacuus, strikes off redundant solution, make liquid level and Nang Kou
Concordantly.
(3) at 3-6 DEG C of temperature, dry 50-70min removes solvent, and inner wall forms not soluble layer A, it is insoluble to obtain inner wall
Capsule body.
(4) the insoluble capsule body of inner wall is coated, forms inner coating layer and exterior coating, obtains inner and outer wall
Insoluble insoluble capsule body, exterior coating with a thickness of 5-10 μm, the overall thickness of inner coating layer and non-soluble layer A are 10-15 μ
m.The flow velocity of coating solution is controlled when coating in 15-25l/h, 45-55 DEG C of inlet air temperature, the composition of coating solution are as follows: ethyl cellulose,
Dibutyl phthalate, magnesium stearate, glycerol, acetone are mixed according to 80-85g:10g:2-3g:1.5-1.8L:1.2-1.5L
It obtains.
Block layer is intumescent plunger (the capsule mouth size of circular piece, size and insoluble capsule body is adapted), preparation
Method are as follows: take the hydroxyethyl cellulose and dried starch of recipe quantity, mix, sieve with 100 mesh sieve, the ethyl alcohol system of mass concentration 75% is added
Softwood, it is granulation, dry, cross 20 mesh sieves, be added magnesium stearate, total mix, using circular die tabletting to get.Wherein, hydroxyl second
Base cellulose, dried starch, ethyl alcohol and magnesium stearate amount ratio be 30-50g:15-20g:2.5-4ml:2-3g, hydroxy ethyl fiber
Element can also be replaced with hypromellose or sodium alginate.
Capsule body, utricule or capsule body of the present invention each mean the part removed except capsule cap in hungry area softgel shell.
The present invention is discussed in detail with specific example below.
Material, reagent and equipment of the present invention are commercially available, wherein Paecilomyces hepiali chen Cs-4 fermentation cordyceps
Raw material is the production of Jiangxi traditional Chinese medicines limited liability company, and bulk pharmaceutical chemicals national drug standard number is Z10899021.
Embodiment 1
Firstly, preparing insoluble capsule body, preparation method are as follows: (1) press methylene chloride, anhydrous propanone and ethyl acetate
According to the mixed solvent that volume ratio 5:0.9:0.2 is mixed to get, ethyl cellulose, the ethyl cellulose that compound concentration is 10% is added
Solution.(2) No. 0 gelatin capsulae vacuus is taken, prepared ethyl cellulose solution is filled into the capsule body of gelatin capsulae vacuus, is struck off
Extra solution keeps liquid level concordant with Nang Kou.(3) at 3 DEG C of temperature, dry 70min removes solvent, and inner wall forms not soluble layer A,
Obtain the insoluble capsule body of inner wall.(4) the insoluble capsule body of inner wall is coated, forms inner coating layer and outer coatings
Layer, obtains the insoluble insoluble capsule body of inner and outer wall.The flow velocity of coating solution is controlled when coating in 15l/h, inlet air temperature
45 DEG C, the composition of coating solution are as follows: ethyl cellulose, dibutyl phthalate, magnesium stearate, glycerol, acetone are according to 80g:
10g:2g:1.5L:1.2L is mixed to get.The exterior coating for the insoluble capsule body being finally prepared is with a thickness of 6 μm, interior coating
The overall thickness of layer and not soluble layer A are 12 μm.
Then, the intumescent plunger of block layer is prepared, method particularly includes: take the hydroxyethyl cellulose and Gan Dian of recipe quantity
Powder, mixing, sieves with 100 mesh sieve, and the ethyl alcohol softwood of mass concentration 75% is added, prepares partial size in 0.1-0.2mm using granulator
Particle, it is dry so that particle moisture 3% hereinafter, cross 20 mesh sieves, magnesium stearate is added, total mix uses circular die
Tabletting obtains the diameter circular piece adaptable with the capsule mouth diameter of insoluble capsule body, i.e. plunger.Wherein, hydroxyethyl cellulose,
The amount ratio of dried starch, ethyl alcohol and magnesium stearate is 30g:15g:2.5ml:2g.
Finally, taking the insoluble capsule body prepared, it is sequentially filled initial bed, medicine layer and separation layer, it then will preparation
Good intumescent plunger inserts insoluble capsule body, which fits closely with utricule inner wall, and the upper surface of plunger and Nang Kou
Concordantly；Put on the capsule cap of No. 0 gelatine capsule again to get product.
The specification of Jinshuibao pulsatile capsules manufactured in the present embodiment is 0.33g/, wherein initial bed is carboxymethyl starch
Sodium, medicine layer are Paecilomyces hepiali chen Cs-4 fermentation cordyceps, and separation layer is sodium carboxymethyl starch；Initial bed, medicine layer, every
The weight ratio of absciss layer and block layer is 0.1:1:0.2:0.4.
Embodiment 2
Firstly, preparing insoluble capsule body, preparation method are as follows: (1) press methylene chloride, anhydrous propanone and ethyl acetate
According to the mixed solvent that volume ratio 5:1.0:0.3 is mixed to get, ethyl cellulose, the ethyl cellulose that compound concentration is 11% is added
Solution.(2) No. 0 gelatin capsulae vacuus is taken, prepared ethyl cellulose solution is filled into the capsule body of gelatin capsulae vacuus, is struck off
Extra solution keeps liquid level concordant with Nang Kou.(3) at 5 DEG C of temperature, dry 60min removes solvent, and inner wall forms not soluble layer A,
Obtain the insoluble capsule body of inner wall.(4) the insoluble capsule body of inner wall is coated, forms inner coating layer and outer coatings
Layer, obtains the insoluble insoluble capsule body of inner and outer wall.The flow velocity of coating solution is controlled when coating in 20l/h, inlet air temperature
50 DEG C, the composition of coating solution are as follows: ethyl cellulose, dibutyl phthalate, magnesium stearate, glycerol, acetone are according to 82g:
10g:2.5g:1.6L:1.4L is mixed to get.The exterior coating for the insoluble capsule body being finally prepared is with a thickness of 5 μm, interior packet
The overall thickness of clothing layer and non-soluble layer A are 10 μm.
Then, the intumescent plunger of block layer is prepared, method particularly includes: take the hypromellose and Gan Dian of recipe quantity
Powder, mixing, sieves with 100 mesh sieve, and the ethyl alcohol softwood of mass concentration 75% is added, prepares partial size in 0.1-0.2mm using granulator
Particle, it is dry so that particle moisture 3% hereinafter, cross 20 mesh sieves, magnesium stearate is added, total mix uses circular die
Tabletting obtains the diameter circular piece adaptable with the capsule mouth diameter of insoluble capsule body, i.e. plunger.Wherein, hydroxypropyl methylcellulose
Element, dried starch, ethyl alcohol and magnesium stearate amount ratio be 40g:18g:3.5ml:2.5g.
Finally, taking the insoluble capsule body prepared, it is sequentially filled initial bed, medicine layer and separation layer, it then will preparation
Good intumescent plunger inserts insoluble capsule body, which fits closely with utricule inner wall, and the upper surface of plunger and Nang Kou
Concordantly；Put on the capsule cap of No. 0 gelatine capsule again to get product.
The specification of Jinshuibao pulsatile capsules manufactured in the present embodiment is 0.33g/, wherein initial bed is cross-linked carboxymethyl
Sodium cellulosate, medicine layer are Paecilomyces hepiali chen Cs-4 fermentation cordyceps, and separation layer is sodium carboxymethyl starch；Initial bed, medicine
The weight ratio of nitride layer, separation layer and block layer is 0.15:1:0.2:0.5.
Embodiment 3
Firstly, preparing insoluble capsule body, preparation method are as follows: (1) press methylene chloride, anhydrous propanone and ethyl acetate
According to the mixed solvent that volume ratio 5:1.1:0.3 is mixed to get, ethyl cellulose, the ethyl cellulose that compound concentration is 12% is added
Solution.(2) No. 0 gelatin capsulae vacuus is taken, prepared ethyl cellulose solution is filled into the capsule body of gelatin capsulae vacuus, is struck off
Extra solution keeps liquid level concordant with Nang Kou.(3) at 6 DEG C of temperature, dry 50min removes solvent, and inner wall forms not soluble layer A,
Obtain the insoluble capsule body of inner wall.(4) the insoluble capsule body of inner wall is coated, forms inner coating layer and outer coatings
Layer, obtains the insoluble insoluble capsule body of inner and outer wall.The flow velocity of coating solution is controlled when coating in 25l/h, inlet air temperature
55 DEG C, the composition of coating solution are as follows: ethyl cellulose, dibutyl phthalate, magnesium stearate, glycerol, acetone are according to 85g:
10g:3g:1.8L:1.5L is mixed to get.The exterior coating for the insoluble capsule body being finally prepared is with a thickness of 10 μm, interior packet
The overall thickness of clothing layer and non-soluble layer A are 15 μm.
Then, the intumescent plunger of block layer is prepared, method particularly includes: take the hydroxyethyl cellulose and Gan Dian of recipe quantity
Powder, mixing, sieves with 100 mesh sieve, and the ethyl alcohol softwood of mass concentration 75% is added, prepares partial size in 0.1-0.2mm using granulator
Particle, it is dry so that particle moisture 3% hereinafter, cross 20 mesh sieves, magnesium stearate is added, total mix uses circular die
Tabletting obtains the diameter circular piece adaptable with the capsule mouth diameter of insoluble capsule body, i.e. plunger.Wherein, hydroxyethyl cellulose,
The amount ratio of dried starch, ethyl alcohol and magnesium stearate is 50g:20g:4ml:3g.
Finally, taking the insoluble capsule body prepared, it is sequentially filled initial bed, medicine layer and separation layer, it then will preparation
Good intumescent plunger inserts insoluble capsule body, which fits closely with utricule inner wall, and the upper surface of plunger and Nang Kou
Concordantly；Put on the capsule cap of No. 0 gelatine capsule again to get product.
The specification of Jinshuibao pulsatile capsules manufactured in the present embodiment is 0.33g/, wherein initial bed is carboxymethyl starch
Sodium, medicine layer are Paecilomyces hepiali chen Cs-4 fermentation cordyceps, and separation layer is dried starch；Initial bed, medicine layer, separation layer and
The weight ratio of block layer is 0.2:1:0.3:0.6.
Embodiment 4
Firstly, preparing insoluble capsule body, preparation method are as follows: (1) press methylene chloride, anhydrous propanone and ethyl acetate
According to the mixed solvent that volume ratio 5:1.1:0.2 is mixed to get, ethyl cellulose, the ethyl cellulose that compound concentration is 12% is added
Solution.(2) No. 0 gelatin capsulae vacuus is taken, prepared ethyl cellulose solution is filled into the capsule body of gelatin capsulae vacuus, is struck off
Extra solution keeps liquid level concordant with Nang Kou.(3) at 5 DEG C of temperature, dry 55min removes solvent, and inner wall forms not soluble layer A,
Obtain the insoluble capsule body of inner wall.(4) the insoluble capsule body of inner wall is coated, forms inner coating layer and outer coatings
Layer, obtains the insoluble insoluble capsule body of inner and outer wall.The flow velocity of coating solution is controlled when coating in 20l/h, inlet air temperature
50 DEG C, the composition of coating solution are as follows: ethyl cellulose, dibutyl phthalate, magnesium stearate, glycerol, acetone are according to 82g:
10g:3g:1.7L:1.4L is mixed to get.The exterior coating for the insoluble capsule body being finally prepared is with a thickness of 8 μm, interior coating
The overall thickness of layer and not soluble layer A are 10 μm.
Then, the intumescent plunger of block layer is prepared, method particularly includes: the sodium alginate and dried starch of recipe quantity are taken, is mixed
It closes, sieves with 100 mesh sieve, the ethyl alcohol softwood of mass concentration 75% is added, partial size is prepared in of 0.1-0.2mm using granulator
Grain, it is dry so that particle moisture 3% hereinafter, cross 20 mesh sieves, be added magnesium stearate, total mix, with circular die tabletting,
Obtain the diameter circular piece adaptable with the capsule mouth diameter of insoluble capsule body, i.e. plunger.Wherein, sodium alginate, dried starch, second
The amount ratio of pure and mild magnesium stearate is 35g:17g:3.5ml:2g.
Finally, taking the insoluble capsule body prepared, it is sequentially filled initial bed, medicine layer and separation layer, it then will preparation
Good intumescent plunger inserts insoluble capsule body, which fits closely with utricule inner wall, and the upper surface of plunger and Nang Kou
Concordantly；Put on the capsule cap of No. 0 gelatine capsule again to get product.
The specification of Jinshuibao pulsatile capsules manufactured in the present embodiment is 0.33g/, wherein initial bed is the poly- second dimension of crosslinking
Ketone, medicine layer are Paecilomyces hepiali chen Cs-4 fermentation cordyceps, and separation layer is cyclodextrin；Initial bed, medicine layer, separation layer and
The weight ratio of block layer is 0.1:1:0.3:0.5.
Embodiment 5
Firstly, preparing insoluble capsule body, preparation method are as follows: (1) press methylene chloride, anhydrous propanone and ethyl acetate
According to the mixed solvent that volume ratio 5:1.0:0.3 is mixed to get, ethyl cellulose, the ethyl cellulose that compound concentration is 10% is added
Solution.(2) No. 0 gelatin capsulae vacuus is taken, prepared ethyl cellulose solution is filled into the capsule body of gelatin capsulae vacuus, is struck off
Extra solution keeps liquid level concordant with Nang Kou.(3) at 4 DEG C of temperature, dry 55min removes solvent, and inner wall forms not soluble layer A,
Obtain the insoluble capsule body of inner wall.(4) the insoluble capsule body of inner wall is coated, forms inner coating layer and outer coatings
Layer, obtains the insoluble insoluble capsule body of inner and outer wall.The flow velocity of coating solution is controlled when coating in 19l/h, inlet air temperature
52 DEG C, the composition of coating solution are as follows: ethyl cellulose, dibutyl phthalate, magnesium stearate, glycerol, acetone are according to 81g:
10g:2.5g:1.6L:1.3L is mixed to get.The exterior coating for the insoluble capsule body being finally prepared is with a thickness of 6 μm, interior packet
The overall thickness of clothing layer and non-soluble layer A are 11 μm.
Then, the intumescent plunger of block layer is prepared, method particularly includes: take the hydroxyethyl cellulose and Gan Dian of recipe quantity
Powder, mixing, sieves with 100 mesh sieve, and the ethyl alcohol softwood of mass concentration 75% is added, prepares partial size in 0.1-0.2mm using granulator
Particle, it is dry so that particle moisture 3% hereinafter, cross 20 mesh sieves, magnesium stearate is added, total mix uses circular die
Tabletting obtains the diameter circular piece adaptable with the capsule mouth diameter of insoluble capsule body, i.e. plunger.Wherein, hydroxyethyl cellulose,
The amount ratio of dried starch, ethyl alcohol and magnesium stearate is 35g:20g:3ml:3g.
Finally, taking the insoluble capsule body prepared, it is sequentially filled initial bed, medicine layer and separation layer, it then will preparation
Good intumescent plunger inserts insoluble capsule body, which fits closely with utricule inner wall, and the upper surface of plunger and Nang Kou
Concordantly；Put on the capsule cap of No. 0 gelatine capsule again to get product.
The specification of Jinshuibao pulsatile capsules manufactured in the present embodiment is 0.33g/, wherein initial bed is by low substitution hydroxyl
Third methylcellulose and sodium carboxymethyl starch are mixed according to the weight ratio of 1:1, and medicine layer is Paecilomyces hepiali chen Cs-4 hair
Ferment cordyceps, separation layer are glucose；Initial bed, medicine layer, separation layer and block layer weight ratio be 0.2:1:0.2:
0.5。
Comparative example 1
This comparative example the difference from embodiment 1 is that, the preparation method of insoluble capsule body is the inner wall that will be prepared
Insoluble capsule body of the capsule body of not soluble layer A (5 μm thick) as final pulsatile capsules is formed, that is, is preparing insoluble capsule
Coatings are formed in gelatine capsule shell not over coating during body.Remaining is the same as embodiment 1.
Comparative example 2
This comparative example the difference from example 2 is that, the preparation method of insoluble capsule body is directly by No. 0 gelatine capsule
Capsule body be coated, softgel shell inner and outer wall formed coatings, obtain insoluble capsule body.The method and implementation of coating
Example 2 is identical, remaining operation is also same as Example 2.The inner wall for the insoluble capsule body being prepared is coated 3 μm of thickness, outer wall
5 μm of thickness of coating.
Comparative example 3
This comparative example the difference from embodiment 1 is that, in the preparation process of insoluble capsule body, the coating solution of use is formed
Are as follows: ethyl cellulose, magnesium stearate, ethyl alcohol are mixed according to the ratio of 82g:2g:3L.Remaining is the same as embodiment 1.
Comparative example 4
This comparative example the difference from example 2 is that, during preparing insoluble capsule body, use concentration be 11%
Ethyl cellulose solution, but its solvent is that benzene and ethyl alcohol are obtained by mixing according to volume ratio 3:2.Remaining is the same as embodiment 2.
Comparative example 5
This comparative example the difference from example 2 is that, there is no separation layer, insoluble glue in the Jinshuibao pulsatile capsules of preparation
Utricule is successively initial bed (croscarmellose sodium), medicine layer (Paecilomyces hepiali chen Cs-4 ferment cordyceps sinensis from top to bottom
Bacterium powder) and block layer (with embodiment 2), and the weight ratio of initial bed, medicine layer and block layer is 0.2:1:0.6.Remaining is the same as real
Apply example 2.
Comparative example 6
This comparative example the difference from example 2 is that, there is no separation layer and initial bed in the Jinshuibao pulsatile capsules of preparation,
After filling Paecilomyces hepiali chen Cs-4 fermentation cordyceps in the capsule body of pulsatile capsules, insert block layer (with embodiment 2), cordyceps sinensis
The weight ratio of bacterium powder and block layer is 1:0.6.Remaining is the same as embodiment 2.
Test case
(1) method that embodiment 1-5 and comparative example 1-4 prepares insoluble capsule body is variant, now examines and is prepared
Insoluble capsule body mainly investigates the appearance character of its cyst wall, as a result thickness, uniformity including not soluble layer and coatings are shown in
Table 1.
Table 1.
As can be seen from Table 1, the not soluble layer for the insoluble capsule body that prepared by comparative example 3 and comparative example 4 is inhomogenous, does not meet
It is required that, it is not necessary to further investigated；Illustrate to prepare composition, the ethyl cellulose of coating material during insoluble capsule body
The solvent composition of solution, which will affect, forms the effect of not soluble layer in the external wall of gelatine capsule and inner wall.
(2) dissolution examination is carried out to the Jinshuibao pulsatile capsules of embodiment 1-5, comparative example 1-2 and comparative example 5-6 preparation
It tests, for dissolution test method referring to " small-radius curve track " in Pharmacopoeia of People's Republic of China version in 2015, dissolution medium is the phosphorus of pH6.8
Hydrochlorate buffer solution, 60min, 120min, 180min, 200min, 220min, 240min, 260min, 280min,
300min and 320min sampling, using Pharmacopoeia of People's Republic of China version in 2015 about under paecilomyces hepiall chen content determination item
Regulation carries out adenosine content (%) measurement.Specific dissolution results are shown in Table 2.
Table 2.
As seen from Table 2, the Jinshuibao pulsatile capsules of embodiment 1-5 preparation start to detect in dissolution fluid in 220min
98% or more is had reached to Cs-4 cordyceps, and in 260min dissolution, drug release rate is fast；Technology provided by the invention
Scheme can prepare timing, quick-acting Jinshuibao pulsatile capsules.In contrast, Jinshuibao arteries and veins prepared by comparative example 1 and comparative example 2
Capsule is rushed, cordyceps can be detected in the dissolution fluid of 60min, during test, the capsule of comparative example 1 is
75min disintegration, drug all dissolve out, and the capsule of comparative example 2 is disintegrated in 80min, and drug all dissolves out.The reason is that system
The insoluble layer thickness low LCL of standby insoluble capsule body, dissolution medium can slowly penetrate capsule, and early stage is caused to have part
Drug-eluting, as the medium entered in capsule body increases, separation layer therein and retardance layer material water swelling cause capsule to collapse
Solution.Influence of the preparation of insoluble capsule body to final products is very big as a result,.The capsule of comparative example 5 is in the molten of 180min
Cordyceps can be detected in liquid out, start the time discharged also earlier, reason is in capsule without filling separation layer,
It is absorbed in expansion process in block layer, has there is drug to start to release, so it is not carried out time controlled released.The capsule of comparative example 6
Compared with comparative example 5, the time for starting release is close, but the drug releasing rate of comparative example 6 is much slower, but in 220min
Release amount of medicine be still similar because block layer absorb expand to disengage from capsule time it is close, and once block layer is de-
From the medicine layer in capsule body starts to discharge, and only the disintegrating agent of bottom can obviously accelerate the rate of release of drug.
To sum up, technical solution provided by the invention can prepare timing, quick-acting Jinshuibao pulsatile capsules, insoluble capsule body
Preparation method and capsule in material filling etc. will affect the quality of product.
The foregoing is only a preferred embodiment of the present invention, but scope of protection of the present invention is not limited thereto,
In the technical scope disclosed by the present invention, any changes or substitutions that can be easily thought of by anyone skilled in the art,
It should be covered by the protection scope of the present invention.
Claims (10)
1. a kind of Jinshuibao pulsatile capsules, which is characterized in that by insoluble capsule body, initial bed, medicine layer, separation layer, retardance
Layer and soluble Capsule composition；Wherein, medicine layer is Paecilomyces hepiali chen Cs-4 fermentation cordyceps, is located at insoluble capsule body
Inside；Initial bed is located at the bottommost of insoluble capsule body；Separation layer is between medicine layer and block layer；Block layer is located at
The open end of insoluble capsule body is fitted closely with insoluble capsule body inner wall, and concordant with the Nang Kou of insoluble capsule body.
2. Jinshuibao pulsatile capsules according to claim 1, which is characterized in that insoluble capsule body the preparation method comprises the following steps:
(1) ethyl cellulose solution is prepared；(2) ethyl cellulose solution is filled into the capsule body of gelatin capsulae vacuus, is struck off extra molten
Liquid keeps liquid level concordant with Nang Kou；(3) solvent is dried and removed, inner wall forms not soluble layer A, obtains the insoluble capsule body of inner wall；
(4) the insoluble capsule body of inner wall is coated, forms inner coating layer and exterior coating, it is insoluble obtains inner and outer wall
Insoluble capsule body.
3. Jinshuibao pulsatile capsules according to claim 2, which is characterized in that the mass concentration of ethyl cellulose solution is
10-12%, solvent are that methylene chloride, anhydrous propanone and ethyl acetate are mixed to get according to volume ratio 5:0.9-1.1:0.2-0.3
Mixed solvent.
4. Jinshuibao pulsatile capsules according to claim 2, which is characterized in that
Drying condition described in step (3) is 3-6 DEG C of temperature, drying time 50-70min；
With a thickness of 5-10 μm, the overall thickness of inner coating layer and non-soluble layer A are the exterior coating of insoluble capsule body in step (4)
10-15μm。
5. Jinshuibao pulsatile capsules according to claim 2, which is characterized in that coating method described in step (4) are as follows: match
Coating solution processed, control are coated flow velocity 15-25l/h and 45-55 DEG C of inlet air temperature, are coated.
6. Jinshuibao pulsatile capsules according to claim 5, which is characterized in that the composition of coating solution are as follows: ethyl cellulose,
Dibutyl phthalate, magnesium stearate, glycerol, acetone are mixed according to 80-85g:10g:2-3g:1.5-1.8L:1.2-1.5L
It obtains.
7. Jinshuibao pulsatile capsules according to claim 1, which is characterized in that the block layer is intumescent plunger,
The preparation method comprises the following steps: taking the hydroxyethyl cellulose and dried starch of recipe quantity, mix, sieve with 100 mesh sieve, the second of mass concentration 75% is added
Alcohol softwood, it is granulation, dry, cross 20 mesh sieves, be added magnesium stearate, total mix, tabletting to get.
8. Jinshuibao pulsatile capsules according to claim 7, which is characterized in that hydroxyethyl cellulose, dried starch, ethyl alcohol and
The amount ratio of magnesium stearate is 30-50g:15-20g:2.5-4ml:2-3g；
Wherein, hydroxyethyl cellulose can be replaced with hypromellose or sodium alginate.
9. Jinshuibao pulsatile capsules according to claim 1-7, which is characterized in that initial bed, medicine layer, isolation
The weight ratio of layer and block layer is 0.1-0.2:1:0.2-0.3:0.4-0.6.
10. Jinshuibao pulsatile capsules according to claim 1-7, which is characterized in that
Initial bed is disintegrating agent, selected from sodium carboxymethyl starch, croscarmellose sodium, the poly- second dimension ketone of crosslinking and low substitution hydroxyl
One or both of third methylcellulose；
Separation layer is selected from one of sodium carboxymethyl starch, dried starch, cyclodextrin and glucose；
Soluble capsule cap is with insoluble capsule body with the capsule cap of the gelatine capsule shell of model.
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| CN1836673A (en) * | 2005-03-23 | 2006-09-27 | 仁和（集团）发展有限公司 | Chinese medicinal soft capsule and method for preparing and controlling the quality of Chinese medicinal soft capsule |
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| CN1836673A (en) * | 2005-03-23 | 2006-09-27 | 仁和（集团）发展有限公司 | Chinese medicinal soft capsule and method for preparing and controlling the quality of Chinese medicinal soft capsule |
| CN101317827A (en) * | 2007-06-06 | 2008-12-10 | 中国科学院上海药物研究所 | Terbutaline impulse formulation and preparation method thereof |
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