CN101732261B - Stable type compound pellet, preparation method thereof and capsule containing same - Google Patents
Stable type compound pellet, preparation method thereof and capsule containing same Download PDFInfo
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- CN101732261B CN101732261B CN2010100448556A CN201010044855A CN101732261B CN 101732261 B CN101732261 B CN 101732261B CN 2010100448556 A CN2010100448556 A CN 2010100448556A CN 201010044855 A CN201010044855 A CN 201010044855A CN 101732261 B CN101732261 B CN 101732261B
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Abstract
The invention discloses a stable type compound pellet, a preparation method thereof and a capsule containing the same. The stable type compound pellet is provided with a film coating layer, a main medicine layer, an isolation layer and a pill core from the outside to the inside. The main medicine layer is positioned between the film coating layer and the isolation layer, and the pill core is sealed in the isolation layer. The medicinal effective component of the main medicine layer is vitamin B12, and the mass of the vitamin B12 is 3-10% of the mass of the total solid of the main medicine layer. The medicinal effective components of the pill core are vitamin B1 and vitamin B6, and the mass ratio of the vitamin B1 to the vitamin B6 is 1:0.5-2 (W/W). The stable type compound pellet is prepared by adopting the procedures of pelletizing and coating. At a storage state, the vitamin B12 can not contact with the vitamin B1 and the vitamin B6 in the pill core, thereby avoiding the degradation of medicinal components because of mutual reactions and prolonging the storage time limit.
Description
Technical field the present invention relates to a kind of stable type compound pellet, particularly, relates to a kind of vitamin B that contains
1, vitamin B
6, vitamin B
12Stable type compound pellet, prepare the method for this micropill and contain the capsule of this stable type compound pellet.
Background technology owing to have multiple effective medicinal components and trace element in the prescription, might react to each other between the different effective medicinal components in the same prescription in existing compound preparation, and effective medicinal components is degraded.Therefore, in the process of storing, the different effective medicinal components in the compound preparation are degraded because be in contact with one another through regular meeting, thereby have influence on the bin stability of compound preparation, have reduced drug effect and have shortened shelf-life of compound preparation.As the three-dimensional B sheet of frequent use, it is with vitamin B
1, B
6, B
12Get according to the film-making of certain mass mixed, be applicable to the treatment vitamin B
1, B
6, B
12Mononeuropathy becomes or multiple peripheral neuritis due to deficiency disease and the different causes of disease of treatment.Because vitamin B
12Very unstable, can with tablet in vitamin B
1And vitamin B
6The reaction and degrade.Therefore, three-dimensional B sheet is stored half a year to one year, vitamin B in accordance with regulations
12Content will reduce to defective.
In the prior art, in order to overcome the shortcoming of compound preparation stable type difference, need add a large amount of stabilizing agents when film-making, this often causes tablet volume bigger, is difficult for swallowing.
The preparation method of the nano-sphere/microsphere double-embedding system of a kind of vitamin A, vitamin E is disclosed among the patent of invention ZL200710192023.7 " preparation method of the nano-sphere/microsphere double-embedding system of a kind of vitamin A, vitamin E ", be that vitamin A is made dispersive nanosphere suspension earlier, the remix vitamin E is made the material core, makes microsphere at outer coating at last.This patent provides a kind of different effective medicinal components has been distributed to method in the different medicine layers, but its main purpose is in order to realize the effect of substep release medicinal effective ingredient, do not solve between the composition that reacts to each other and degrade, the short problem of effective storage life limit of medicine because of being in contact with one another.
Summary of the invention the purpose of this invention is to provide a kind of stable type compound pellet, has avoided each other easily the material of reaction to degrade owing to being in contact with one another, thus make the various active composition can be under the individual system stable existence, the prolongation shelf life.Another object of the present invention has provided the preparation method for preparing this stable type compound pellet.Another object of the present invention provides a kind of capsule that contains this stable type compound pellet.
For achieving the above object, a kind of stable type compound pellet of the present invention comprises film-coat layer and ball core, also comprises principal agent layer and sealing coat, and this stable type compound pellet is respectively from outside to inside: film-coat layer, principal agent layer, sealing coat, ball core; Described principal agent layer contains at least a effective medicinal components between film-coat layer and sealing coat, do not react between each effective medicinal components in this principal agent layer; Described ball core is closed in the sealing coat, contains at least a effective medicinal components and binding agent, does not react between each effective medicinal components in this ball core.Owing to the effective medicinal components that may react is each other placed different medicine layers respectively, is provided with the sealing coat of isolating usefulness between the medicine layer.Can directly not contact between the effective medicinal components that in storage process, can react, degrade because be in contact with one another, prolong the shelf life of micropill thereby avoided effective medicinal components.
A kind of stable type compound pellet of the present invention, the effective medicinal components of described ball core are vitamin B
1, vitamin B
6, vitamin B
1And vitamin B
6Mass ratio be 1: 0.5～2 (W/W); The effective medicinal components of described principal agent layer is a vitamin B
12, vitamin B
12Quality be 3%～10% of the total solid quality of principal agent layer; Described sealing coat contains one or more compositions that are selected from hydroxypropyl emthylcellulose, PEG400, pigment, gelatin, titanium dioxide, the Opadry coating materials (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system); Described film-coat layer contains one or more compositions that are selected from hydroxypropyl emthylcellulose, PEG400, pigment, gelatin, titanium dioxide, the Opadry coating materials (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system).Because vitamin B
12Place the principal agent layer, vitamin B
1And vitamin B
6Mix to be placed in the ball core, middlely separate, make under the stored condition vitamin B by inert sealing coat
12Not can with the vitamin B in the ball core
1, vitamin B
6Contact is degraded because react to each other thereby avoided medicinal ingredient, has prolonged the time limit of storing.
The present invention is used to prepare the method for described a kind of stable type compound pellet, and this micropill contains four-layer structure, and ball core and principal agent layer contain effective medicinal components, are provided with sealing coat between them, and the principal agent layer is provided with the film-coat layer outward, and preparation method is:
Step 1, preparation contains the ball core of at least a effective medicinal components: with at least a effective medicinal components and binding agent mix homogeneously, making diameter in pellet processing machine is the ball core of 500～1000 μ m;
Step 2, parcel sealing coat: will not react and also can make insulating liquid by effectively isolated one or more compositions, and the ball core that makes in the step 1 will be carried out the coating operation with fluidized-bed coating machine with ball core, principal agent layer effective medicinal components;
Step 3, parcel principal agent layer: at least a effective medicinal components and pharmaceutic adjuvant composition are mixed and made into main liquid, the micropill that makes in the step 2 are carried out the coating operation with fluidized-bed coating machine;
Step 4, wrap film clothing layer: will not react and also can make film-coat liquid by effectively isolated one or more compositions, and the micropill that makes in the step 3 will be carried out the coating operation with fluidized-bed coating machine with principal agent layer effective medicinal components.
Concrete, step 1 is with the effective medicinal components vitamin B
1And vitamin B
6With binding agent, be that the sodium carboxymethyl cellulose of water or 0.5%～5% or carboxymethyl starch sodium solution or mass concentration are 1%～5% starch slurry or mass concentration at 2%～10% white sugar water solution mix homogeneously, making diameter in pellet processing machine is the ball core of 500～1000 μ m.
Step 2, hydroxypropyl emthylcellulose, pigment and water are pressed mass ratio 18: (5～15): (100～300), or the Opadry coating materials is (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system), or gelatin, white sugar, pigment and water were by mass ratio 5: 10: 4: 100 make insulating liquid, with fluidized-bed coating machine the ball core that makes in the step 1 are carried out the coating operation.As a kind of optimization, step 2 can be made insulating liquid by mass ratio with hydroxypropyl emthylcellulose, pigment and water at 18: 9: 220, with fluidized-bed coating machine the ball core that makes in the step 1 is carried out the coating operation.
Step 3 will contain 0.5%～2% vitamin B of medicinal effective ingredient
12Solution and 18% the Gonak equal-volume mixed that contains medicinal adjunct ingredient are made main liquid, with fluidized-bed coating machine to the parcel that makes in the step 2 micropill of sealing coat carry out the coating operation, make vitamin B after the coating operation
12Quality be 3%～10% of the total solid quality of principal agent layer.
Step 4, hydroxypropyl emthylcellulose, PEG400, pigment and water are pressed mass ratio 18: (1～10): (5～15): (100～300), or the Opadry coating materials is (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system), or hydroxypropyl emthylcellulose, PEG400, pigment, titanium dioxide and water are by mass ratio 18: (1～10): (5～15): (2～15): (100～300) make film-coat liquid, with fluidized-bed coating machine to the parcel that makes in the step 3 micropill of principal agent layer carry out the coating operation.As a kind of optimization, step 4 can be with hydroxypropyl emthylcellulose, PEG400, pigment and water by mass ratio 18: 3: 9: 220 make film-coat liquid, with fluidized-bed coating machine to the parcel that makes in the step 3 micropill of principal agent layer carry out the coating operation.
With described vitamin B
1, vitamin B
6After binding agent mixed, to make size be 500～1000 μ m, contain vitamin B
1And vitamin B
6The ball core.Respectively insulating liquid, main liquid and film-coat liquid layering be sprayed on ball core on and form the multiple coatings structure thereafter.Make vitamin B
12Not can with the vitamin B in the ball core
1, vitamin B
6Contact is degraded because react to each other thereby avoided medicinal ingredient, has prolonged the time limit of storing.Again because vitamin B
12In the coating operation, be to be sprayed on the micropill uniformly, thereby avoided vitamin B
12Defective pockety.
A kind of stable type compound pellet capsule of the present invention, described capsule contains stable type compound pellet.Owing to stable type compound pellet is placed in the capsule, makes things convenient for user to swallow.In addition, also avoided the rolling of micropill to cause the breakage of outer membrane clothing layer, further guaranteed the stability that this stable type compound pellet is stored with mutual collision friction.
Contrast test: the vitamin B of prior art for preparing
1, B
6, B
12The former tablet samples of three-dimensional plate (plastic bottle), the stable type compound pellet sample (plastic bottle) with according to the present invention's preparation carries out trimestral accelerated test under the similarity condition, detect vitamin B wherein
12Content to investigate vitamin B
12Stability.
Test method is as follows:
1, test site: Foochow Min Hai pharmaceutcal corporation, Ltd.
2, test period: year October in May, 2009 to 2009.
3, subjects:
The vitamin B of prior art for preparing
1, B
6, B
12Three-dimensional plate, promptly former tablet samples, every vitamin B
1Content 100mg, vitamin B
6Content 100mg, vitamin B
12Content 0.2mg;
By the stable type compound pellet of the present invention's preparation, i.e. stable type compound pellet sample, wherein vitamin B in the ball core
1And vitamin B
6The mixing quality ratio be 1: 1, binding agent is a water; The insulating liquid that is used to wrap up sealing coat is made by mass ratio by hydroxypropyl emthylcellulose, pigment and water at 18: 9: 220; Be used to wrap up the main liquid of principal agent layer by 0.5%～2% vitamin B that contains medicinal effective ingredient
12Solution and 18% the Gonak equal-volume mixed that contains medicinal adjunct ingredient are made; Film-coat liquid hydroxypropyl emthylcellulose, PEG400, pigment and the water that is used for wrap film clothing layer was by mass ratio 18: 3: 9: 220 make.
4, experimental condition: accelerated test is about to two samples, and to be placed on temperature together be 40 ℃ ± 2 ℃, and relative humidity is 75% ± 5%, and illumination is in the growth cabinet of 4500lx ± 500lx three months.
5, vitamin B
12Detection method (ministry standard WS-10001-(HD-0206)-2002): measure according to high performance liquid chromatography (2005 editions two appendix VD of Chinese Pharmacopoeia, 28 pages of appendix).
Chromatographic condition: with octadecylsilane chemically bonded silica is filler; With 0.1% phosphoric acid (mL/mL) (containing 0.005% (mL/mL) diethylamine) solution-acetonitrile (83: 17) is mobile phase; The detection wavelength is 360nm, and number of theoretical plate is pressed vitamin B
12The peak calculates and is not less than 1500.
Algoscopy: it is fixed that lucifuge operation treating excess syndrome is tested the accurate title of object sample, porphyrize, and precision takes by weighing in right amount (suitable approximately vitamin B
120.2mg) put in the 100mL measuring bottle, it is an amount of to add mobile phase, and sonic oscillation 10 minutes takes out, and is diluted to scale with mobile phase, shakes up, and gets the part solution centrifugal 10 minutes, gets supernatant, as need testing solution.Other gets vitamin B
12The about 10mg of reference substance, the accurate title, decide, and puts in the 100mL measuring bottle, with mobile phase dissolving and be diluted to scale, shake up, precision is measured 10mL, put in the 50mL measuring bottle, be diluted to scale with mobile phase, shake up, precision is measured 5mL, put in the 50mL measuring bottle, be diluted to scale with mobile phase, shake up, in contrast product solution.Precision is measured reference substance solution and each 20 μ L of need testing solution, injects chromatograph of liquid respectively, and the record chromatogram is pressed external standard method with calculated by peak area, promptly.
6, testing result: get each 3 in the prepared sample of two kinds of different process of 0 month and 3 months respectively, detect by above method, testing result is as follows:
Table 1
7, analyze: as table 1 as can be known, vitamin B in the former tablet samples of prior art for preparing
12Content decrease speed very fast (after 3 months content descend be about 10%), and vitamin B in the prepared stable type compound pellet sample of the present invention
12Content maintains a stable level.
The present invention is further detailed explanation below in conjunction with the drawings and specific embodiments for description of drawings:
Fig. 1 is the generalized section of stable type compound pellet of the present invention.
The specific embodiment as shown in Figure 1, a kind of stable type compound pellet of the present invention, it comprises film-coat layer and ball core, also comprises principal agent layer and sealing coat, and this stable type compound pellet is respectively from outside to inside: film-coat layer 1, principal agent layer 2, sealing coat 3, ball core 4; Described principal agent layer 2 contains at least a effective medicinal components between film-coat layer 1 and sealing coat 3, do not react between each effective medicinal components in this principal agent layer; Described ball core 4 is closed in the sealing coat 3, contains at least a effective medicinal components and binding agent, does not react between each effective medicinal components in this ball core.
A kind of above-mentioned stable type compound pellet, the effective medicinal components of described principal agent layer 2 are vitamin B
12, vitamin B
12Quality be 3%～10% of principal agent layer 2 total solid quality; The effective medicinal components of described ball core 4 is a vitamin B
1And vitamin B
6, vitamin B
1And vitamin B
6Mass ratio be 1: 0.5～2 (W/W); Described sealing coat 3 contains and is selected from one or more compositions in hydroxypropyl emthylcellulose, PEG400, pigment, gelatin, titanium dioxide, the Opadry coating materials (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system); Described film-coat layer 1 contains and is selected from one or more compositions in hydroxypropyl emthylcellulose, PEG400, pigment, gelatin, titanium dioxide, the Opadry coating materials (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system).
The step for preparing a kind of stable type compound pellet of the present invention is:
Step 1, preparation contains the ball core of at least a effective medicinal components: with at least a effective medicinal components and an amount of binding agent mix homogeneously, making diameter in pellet processing machine is the ball core of 500～1000 μ m;
Step 2, parcel sealing coat: will not react and also can make insulating liquid by effectively isolated one or more compositions, and the ball core that makes in the step 1 will be carried out the coating operation with fluidized-bed coating machine with ball core, principal agent layer effective medicinal components;
Step 3, parcel principal agent layer: at least a effective medicinal components and other pharmaceutic adjuvant compositions are mixed and made into main liquid, the micropill that makes in the step 2 are carried out the coating operation with fluidized-bed coating machine;
Step 4, wrap film clothing layer: will not react and also can make film-coat liquid by effectively isolated one or more compositions, and the micropill that makes in the step 3 will be carried out the coating operation with fluidized-bed coating machine with principal agent layer effective medicinal components.
Conventional method is all adopted in the pill operation in the preparation method of stable type compound pellet of the present invention and the filling of coating operation and pellet capsule.(Cui Fude chief editor, pharmaceutics, ISBN-117-05649-5,143-154 page or leaf)
A kind of preferred as the preparation method of stable type compound pellet of the present invention:
The effective medicinal components that contains in the ball core of step 1 preparation is a vitamin B
1And vitamin B
6, vitamin B
1And vitamin B
6Mixing ratio (mass ratio) be 1: 0.5～2.Described binding agent is water preferably, secondly is that mass concentration is 0.5%～5% sodium carboxymethyl cellulose or carboxymethyl starch sodium solution, is preferably mass concentration and is 1%～5% starch slurry, also can be mass concentration at 2%～10% white sugar water solution.
The prescription of insulating liquid described in the step 2: best is hydroxypropyl emthylcellulose, pigment and water.The mass ratio of hydroxypropyl emthylcellulose, pigment and water can be 18: (5～15): (100～300), preferably 18: 9: 220.Next is Opadry coating materials (commercial goods is purchased in Shanghai Colorcon Coating Technology Co., Ltd), and by specification requires to use.Can also be that gelatin, white sugar, pigment and water, mass ratio are 5: 10: 4: 100, each material wherein all can adjust in 25% scope.
Main liquid described in the step 3 is 0.5%～2% vitamin B
12Solution and 18% Gonak equal proportion are mixed.Make vitamin B after the coating operation
12Quality be 3%～10% of the total solid quality of principal agent layer.
The liquid of film-coat described in the step 4 prescription: best is that hydroxypropyl emthylcellulose, PEG400, pigment and water, their mass ratio can be 18: (1～10): (5～15): (100～300), preferably 18: 3: 9: 220.Next is Opadry coating materials (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system) (commercial goods is purchased in Shanghai Colorcon Coating Technology Co., Ltd), and by specification requires to use.Can also be that hydroxypropyl emthylcellulose, PEG400, pigment, titanium dioxide and water, their mass ratio can be 18: (1～10): (5～15): (2～15): (100～300), preferably 18: 3: 9: 4: 220.
Embodiment 1
With vitamin B
1And vitamin B
6With 1: 1 (W/W) mix homogeneously of mass ratio, add suitable quantity of water as binding agent, making diameter in pellet processing machine is the ball core of 500～1000 μ m.Secondly, hydroxypropyl emthylcellulose, pigment and water are mixed and made into insulating liquid with mass ratio at 18: 9: 220, spray to ball core skin with fluidized-bed coating machine.Then, with 1% vitamin B
12Solution and 18% Gonak equal proportion mixed main liquid, spray to the ball core skin that has wrapped up sealing coat with fluidized-bed coating machine.At last, with hydroxypropyl emthylcellulose, PEG400, pigment and water with mass ratio 18: 3: 9: 220 are mixed and made into film-coat liquid, spray to the outermost layer of micropill with fluidized-bed coating machine.
Embodiment 2
With vitamin B
1And vitamin B
6With 1: 2 (W/W) mix homogeneously of mass ratio, add suitable quantity of water as binding agent, making diameter in pellet processing machine is the ball core of 500～1000 μ m.Secondly, with gelatin, white sugar, pigment and water by mass ratio 5: 10: 4: 100 are mixed and made into insulating liquid, spray to ball core skin with fluidized-bed coating machine.Then, with 2% vitamin B
12Solution and 18% Gonak equal proportion mixed main liquid, spray to the ball core skin that has wrapped up sealing coat with fluidized-bed coating machine.At last, Opadry coating materials (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system) is made film-coat liquid by product description, spray to the outermost layer of micropill with fluidized-bed coating machine.
Embodiment 3
With vitamin B
1And vitamin B
6With 1: 0.5 (W/W) mix homogeneously of mass ratio, add suitable quantity of water as binding agent, making diameter in pellet processing machine is the ball core of 500～1000 μ m.Secondly, Opadry coating materials (commercially available, Shanghai Colorcon Coating Technology Co., Ltd's system) is made insulating liquid by product description, spray to ball core skin with fluidized-bed coating machine.Then, with 0.5% vitamin B
12Solution and 18% Gonak equal proportion mixed main liquid, spray to the ball core skin that has wrapped up sealing coat with fluidized-bed coating machine.At last, with hydroxypropyl emthylcellulose, PEG400, pigment, titanium dioxide and water by mass ratio 18: 3: 9: be mixed and made into film-coat liquid at 4: 220, spray to the outermost layer of micropill with fluidized-bed coating machine.
Embodiment 4
With vitamin B
1And vitamin B
6With 1: 0.75 (W/W) mix homogeneously of mass ratio, add suitable quantity of water as binding agent, making diameter in pellet processing machine is the ball core of 500～1000 μ m.Secondly, hydroxypropyl emthylcellulose, pigment and water are mixed and made into insulating liquid with mass ratio at 18: 5: 100, spray to ball core skin with fluidized-bed coating machine.Then, with 0.75% vitamin B
12Solution and 18% Gonak equal proportion mixed main liquid, spray to the ball core skin that has wrapped up sealing coat with fluidized-bed coating machine.At last, with hydroxypropyl emthylcellulose, PEG400, pigment and water with mass ratio 18: 1: 5: 100 are mixed and made into film-coat liquid, spray to the outermost layer of micropill with fluidized-bed coating machine.
Embodiment 5
With vitamin B
1And vitamin B
6With 1: 1.5 (W/W) mix homogeneously of mass ratio, add suitable quantity of water as binding agent, making diameter in pellet processing machine is the ball core of 500～1000 μ m.Secondly, hydroxypropyl emthylcellulose, pigment and water are mixed and made into insulating liquid with mass ratio at 18: 15: 300, spray to ball core skin with fluidized-bed coating machine.Then, with 1.5% vitamin B
12Solution and 18% Gonak equal proportion mixed main liquid, spray to the ball core skin that has wrapped up sealing coat with fluidized-bed coating machine.At last, with hydroxypropyl emthylcellulose, PEG400, pigment and water with mass ratio 18: 10: 15: 300 are mixed and made into film-coat liquid, spray to the outermost layer of micropill with fluidized-bed coating machine.
Embodiment 6
With vitamin B
1And vitamin B
6With 1: 1 (W/W) mix homogeneously of mass ratio, add suitable quantity of water as binding agent, making diameter in pellet processing machine is the ball core of 500～1000 μ m.Secondly, hydroxypropyl emthylcellulose, pigment and water are mixed and made into insulating liquid with mass ratio at 18: 9: 220, spray to ball core skin with fluidized-bed coating machine.Then, with 1% vitamin B
12Solution and 18% Gonak equal proportion mixed main liquid, spray to the ball core skin that has wrapped up sealing coat with fluidized-bed coating machine.At last, with hydroxypropyl emthylcellulose, PEG400, pigment, titanium dioxide and water by mass ratio 18: 1: 5: be mixed and made into film-coat liquid at 2: 100, spray to the outermost layer of micropill with fluidized-bed coating machine.
Embodiment 7
With vitamin B
1And vitamin B
6With 1: 1 (W/W) mix homogeneously of mass ratio, add suitable quantity of water as binding agent, making diameter in pellet processing machine is the ball core of 500～1000 μ m.Secondly, hydroxypropyl emthylcellulose, pigment and water are mixed and made into insulating liquid with mass ratio at 18: 9: 220, spray to ball core skin with fluidized-bed coating machine.Then, with 1% vitamin B
12Solution and 18% Gonak equal proportion mixed main liquid, spray to the ball core skin that has wrapped up sealing coat with fluidized-bed coating machine.At last, with hydroxypropyl emthylcellulose, PEG400, pigment, titanium dioxide and water by mass ratio 18: 10: 15: be mixed and made into film-coat liquid at 15: 300, spray to the outermost layer of micropill with fluidized-bed coating machine.
Claims (10)
1. stable type compound pellet, it comprises film-coat layer and ball core, it is characterized in that: it also comprises principal agent layer and sealing coat, this stable type compound pellet is respectively from outside to inside:
Film-coat layer, principal agent layer, sealing coat, ball core;
Described principal agent layer contains at least a effective medicinal components between film-coat layer and sealing coat, do not react between each effective medicinal components in this principal agent layer;
Described ball core is closed in the sealing coat, contains at least a effective medicinal components and binding agent, does not react between each effective medicinal components in this ball core;
The effective medicinal components of described ball core is a vitamin B
1, vitamin B
6, vitamin B
1And vitamin B
6Mass ratio be 1: 0.5～2;
The effective medicinal components of described principal agent layer is a vitamin B
12, vitamin B
12Quality be 3%～10% of the total solid quality of principal agent layer;
Described sealing coat contains one or more compositions that are selected from hydroxypropyl emthylcellulose, PEG400, the gelatin;
Described film-coat layer contains one or more compositions that are selected from hydroxypropyl emthylcellulose, PEG400, the gelatin.
2. be used to prepare the method for a kind of stable type compound pellet as claimed in claim 1, it is characterized in that: preparation method is:
Step 1, preparation contains the ball core of at least a effective medicinal components: with at least a effective medicinal components and binding agent mix homogeneously, making diameter in pellet processing machine is the ball core of 500～1000 μ m;
Step 2, parcel sealing coat: will not react and also can make insulating liquid by effectively isolated one or more compositions, and the ball core that makes in the step 1 will be carried out the coating operation with fluidized-bed coating machine with ball core, principal agent layer effective medicinal components;
Step 3, parcel principal agent layer: at least a effective medicinal components and pharmaceutic adjuvant composition are mixed and made into main liquid, with fluidized-bed coating machine to the parcel that makes in the step 2 micropill of sealing coat carry out the coating operation;
Step 4, wrap film clothing layer: will be react with principal agent layer effective medicinal components and can not make film-coat liquid by effectively isolated one or more compositions, with fluidized-bed coating machine to the parcel that makes in the step 3 micropill of principal agent layer carry out the coating operation.
3. according to the method for a kind of stable type compound pellet of the described preparation of claim 2, it is characterized in that:
Step 1 is with the effective medicinal components vitamin B
1And vitamin B
6With binding agent, be that the sodium carboxymethyl cellulose of water or 0.5%～5% or carboxymethyl starch sodium solution or mass concentration are that 1%～5% starch slurry or mass concentration are 2%～10% white sugar water solution mix homogeneously, making diameter in pellet processing machine is the ball core of 500～1000 μ m.
4. according to the method for a kind of stable type compound pellet of the described preparation of claim 2, it is characterized in that:
Step 3 will contain 0.5%～2% vitamin B of medicinal effective ingredient
12Solution and 18% the Gonak equal-volume mixed that contains medicinal adjunct ingredient are made main liquid, with fluidized-bed coating machine to the parcel that makes in the step 2 micropill of sealing coat carry out the coating operation, make vitamin B after the coating operation
12Quality be 3%～10% of the total solid quality of principal agent layer.
5. according to the method for a kind of stable type compound pellet of the described preparation of claim 2, it is characterized in that:
Step 2 is made insulating liquid with hydroxypropyl emthylcellulose, pigment and water by mass ratio 18: 5～15: 100～300, with fluidized-bed coating machine the ball core that makes in the step 1 is carried out the coating operation.
6. according to the method for a kind of stable type compound pellet of the described preparation of claim 5, it is characterized in that:
Step 2 is made insulating liquid with hydroxypropyl emthylcellulose, pigment and water by mass ratio at 18: 9: 220, with fluidized-bed coating machine the ball core that makes in the step 1 is carried out the coating operation.
7. according to the method for a kind of stable type compound pellet of the described preparation of claim 2, it is characterized in that:
Step 4, hydroxypropyl emthylcellulose, PEG400, pigment and water are pressed mass ratio 18: 1～10: 5～15: 100～300, or hydroxypropyl emthylcellulose, PEG400, pigment, titanium dioxide and water makes film-coat liquid by mass ratio 18: 1～10: 5～15: 2～15: 100～300, with fluidized-bed coating machine to the parcel that makes in the step 3 micropill of principal agent layer carry out the coating operation.
8. according to the method for a kind of stable type compound pellet of the described preparation of claim 7, it is characterized in that:
Step 4, with hydroxypropyl emthylcellulose, PEG400, pigment and water by mass ratio 18: 3: 9: 220 make film-coat liquid, with fluidized-bed coating machine to the parcel that makes in the step 3 micropill of principal agent layer carry out the coating operation.
9. according to the method for a kind of stable type compound pellet of the described preparation of claim 7, it is characterized in that:
Step 4, with hydroxypropyl emthylcellulose, PEG400, pigment, titanium dioxide and water by mass ratio 18: 3: 9: make film-coat liquid at 4: 220, with fluidized-bed coating machine to the parcel that makes in the step 3 micropill of principal agent layer carry out the coating operation.
10. a capsule that contains the described stable type compound pellet of claim 1 is characterized in that: in the described capsule stable type compound pellet is housed.
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| CN103800367B (en) * | 2012-11-14 | 2017-12-05 | 上海上药信谊药厂有限公司 | Treat pharmaceutical composition of hypertension and preparation method thereof |
| CN103463120B (en) * | 2013-09-03 | 2015-10-28 | 福州闽海药业有限公司 | A kind of stable type compound vitamin B tablet and preparation method thereof |
| CN109999056A (en) * | 2019-03-29 | 2019-07-12 | 湖北省八峰药化股份有限公司 | A kind of compound pellet and preparation method thereof containing a variety of amino acid, vitamine minerals |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1943783A (en) * | 2006-09-27 | 2007-04-11 | 常州千红生化制药有限公司 | The preparation of compound digestive enzyme and its preparation method |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1943783A (en) * | 2006-09-27 | 2007-04-11 | 常州千红生化制药有限公司 | The preparation of compound digestive enzyme and its preparation method |
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| CN101732261A (en) | 2010-06-16 |
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Denomination of invention: Stable type compound pellet, preparation method thereof and capsule containing same Effective date of registration: 20161010 Granted publication date: 20110720 Pledgee: Agricultural Bank of China Limited by Share Ltd Fuqing branch Pledgor: Fuzhou Minhai Pharmaceutical Co., Ltd. Registration number: 2016350000109 |
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