CN101190179B - Enteric medicinal composition for treating diabetes and preparation method thereof - Google Patents
Enteric medicinal composition for treating diabetes and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a biguanide anti-diabetes medicine, in particular to a metformin hydrochloride enteric-coated medicine compound. The medicine compound is provided with a. a hollow pill core; b. a biguanide anti-diabetes medicine active component layer which is covered outside the hollow pill core; c. an enteric-coated layer which is covered outside the biguanide anti-diabetes medicine active component layer. The invention also discloses a method of preparing the medicine compound.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for the treatment of diabetes and preparation method thereof.Particularly relate to a kind of biguanides, especially enteric-coated medicament combination of metformin hydrochloride and preparation method thereof.
Background technology
Diabetes are common endocrinopathy, are disability rate, the highest the third-largest diseases of fatality rate after cardiovascular disease, cancer, seriously injure human beings'health.The oral drugs of treatment type 2 diabetes mellitus mainly divide four big class, i.e. sulfonylurea, biguanides, alpha-glucosidase inhibitor and euglycemic agents.The hypoglycemic activity of biguanides is owing to suppress the picked-up of intestinal wall cell to glucose, promote glycolysis and suppress the glycogen heteroplasia, it can not produce the hypoglycemia phenomenon, extensively promoted the use of clinically, this type of medicine comprises phenformin (phenformin), metformin (metformin) and buformin (buformin), what wherein application was the most general is exactly metformin, particularly the hydrochlorate of metformin.Metformin has stomach irritation, it is prepared into enteric coated preparation then can effectively avoids its stimulation to gastric mucosa, reduces the generation of untoward reaction.At the enteric coated preparation of biguanides, existing many correlational studyes in the prior art.
CN1413582A discloses a kind of Dimethyldiguanide hydrochloride enteric solubility tablet and preparation method thereof, adopts adjuvant mixing granulation tablettings such as metformin hydrochloride and starch, dextrin, hydroxypropyl cellulose, and reuse enteric coating powder carries out coating.Yet enteric coatel tablets have the inhomogenous shortcoming of release.CN1561980A discloses a kind of metformin hydrochloride enteric-coated capsule, is that metformin hydrochloride is mixed with polyvinylpyrrolidone, pregelatinized Starch etc., adopts HPMC system soft material, the enteric coated capsule of packing into behind granulate back, oven dry, the granulate.The metformin enteric coated capsule of this method preparation, for the prescription height of enteric capsule shell, poor controllability also is easy to generate the inhomogenous phenomenon of release.Therefore, still need a kind of easy to prepare, cost is low, release is stable, equal once good biguanides enteric-coated medicament combinations.
Summary of the invention
By discovering, the biguanides antidiabetic medicine is added suitable adhesive be mixed with medicine-feeding coating liquid, with medicine liquid spray on the celphere surface, atomization drying is also controlled the medicine carrying piller that the coating weightening finish can be prepared suitable drug loading, again the medicine carrying piller is adopted the high molecular polymer coating with spray pattern, thereby make the enteric coated micropill of biguanides.The mode of this ball core spraying medicine-feeding can make surperficial sphericity, uniform particle diameter and the yield rate etc. of micropill reach more satisfactory effect, and the enteric coated micropill release homogeneous of prepared biguanides has good quality controllability.Adopt enteric-coated medicament combination of the present invention, solved the problem of principal agent gastric irritation, effectively reduce individual variation.
The enteric-coated medicament combination that the purpose of this invention is to provide a kind of biguanides antidiabetic medicine, particularly metformin hydrochloride.Said composition has a. celphere; B. biguanides antidiabetic medicine active component layer, this active component layer is coated on the outside of celphere; C. enteric coating layer, this enteric coating layer is coated on the outside of biguanides antidiabetic medicine active component layer.Biguanides antidiabetic medicine wherein includes but not limited to phenformin, metformin and buformin etc., preferred metformin hydrochloride.
The active constituents of medicine layer can contain at least a binding agent, play the effect of bonding active component and ball core, binding agent can be a medicament field binding agent commonly used, for example can be cellulose and derivant thereof, macromolecular materials such as ethene polymers, concrete kind includes but not limited to hydroxypropyl emthylcellulose, hydroxypropyl emthylcellulose acetic acid succinate, polyvinylpyrrolidone, ethyl cellulose, hydroxyethyl-cellulose, hydroxyethylmethyl-cellulose, hydroxypropyl cellulose, Lac, zein etc. or their mixture, be preferably hydroxypropyl emthylcellulose, polyvinylpyrrolidone, hydroxypropyl cellulose or their mixture, more preferably hydroxypropyl emthylcellulose. the viscosity of hydroxypropyl emthylcellulose preferably can be 3cps～100cps, more preferably 3cps～50cps, preferred especially 3cps～20cps, especially 6cps. active constituents of medicine layer can also further contain at least a antitack agent, concrete kind includes but not limited to Pulvis Talci, micropowder silica gel, magnesium stearate etc. are preferably Pulvis Talci.
The enteric coating layer of the present composition contains at least a high molecular polymer that stops medicine stripping in gastric juice that has, and concrete kind includes but not limited to Youteqi (Eudragit) L, Youteqi (Eudragit) S, succinic acid hydroxypropylmethylcellulose acetate methylcellulose, HPMCP, polyvinyl acetate phthalic acid ester, Youteqi (Eudragit) RL, Youteqi (Eudragit) RS or their mixture.Preferred Youteqi (Eudragit) L100-55.Enteric coating layer can further include at least a antitack agent, and concrete kind includes but not limited to Pulvis Talci, micropowder silica gel, magnesium stearate etc., is preferably Pulvis Talci.Enteric coating layer can further include at least a plasticizer, and concrete kind includes but not limited to PEG400-10000, triethyl citrate etc., preferred PEG400-10000, most preferably Macrogol 4000.
Enteric coating weightening finish should be 20%～50% in the present composition, and is preferred 20%～40%, preferred especially 20%～35%, and most preferably 27%～30%.
Celphere in the present composition can commercially obtain, can also adopt and extrude methods such as round as a ball, fluidized bed prilling or method disclosed by the invention prepares, its kind includes but not limited to microcrystalline Cellulose ball, sugar pill, starch ball etc., is preferably the microcrystalline Cellulose ball.The particle diameter of blank core can 150 μ m～1000 μ m, preferred 250 μ m～900 μ m, more preferably 400 μ m～800 μ m, most preferably 610 μ m～750 μ m.
Slow releasing composition of the present invention can also further add opacifier, for example titanium dioxide etc.; Coloring agent, for example lemon yellow, rust red etc.; Aromatic, for example Herba Menthae essence, Fructus Citri Limoniae essence, flavoring orange essence etc.; Or sweeting agent, for example A Siba is sweet, vanillin, sorbitol, mannitol etc.
Another object of the present invention provides a kind of preparation method of biguanides anti-diabetic enteric-coated medicament combination.Described preparation method comprises:
A. get active component, binding agent, add an amount of solvent, heating for dissolving under stirring stirs.Get celphere and place fluid bed one-step palletizing coating pan, with the above-mentioned medicinal liquid coating of under stirring, adding medicine to.
B. get coating polymer, plasticizer, add an amount of dissolution with solvents.Get the medicine carrying micropill for preparing among a and place fluid bed one-step palletizing coating pan, above-mentioned medicinal liquid is carried out enteric coating under stirring.
Wherein, can further include among a and the b and in coating solution, add antitack agent before the coating, stir into the step of suspension.
Solvent in the said method can be water, ethanol, propylene glycol, chloroform, acetone etc. or their mixture.Preferred water, ethanol or their mixture.
The present invention also further provides a kind of preparation method that is applicable to the celphere of pharmaceutical composition of the present invention on the other hand.
This method is selected centrifugal one-step palletizing coating machine for use, and water is a binding agent, preparation microcrystalline Cellulose parent nucleus.Process conditions are: binder dosage is 0.5～3 times of adjuvant, and the spray pump rotating speed is 10～50r/min, and engine speed is greater than 100r/min, and the round as a ball time is 0.5～10 minute.Preferably, binder dosage is 1.1～1.2 times of adjuvant, and the spray pump rotating speed is 20～30r/min, and engine speed is greater than 300r/min, and the round as a ball time is 1 minute
Carry out 10 batches repetitive operation, the results are shown in Table 1.Satisfactory microcrystalline Cellulose nuclear core particle is mixed, as the celphere of next step technical study.
Description of drawings
Four batches of metformin hydrochloride enteric-coated capsular releases of Fig. 1 embodiment 11 preparations
The specific embodiment
The following specific embodiment only is used for illustrating the present invention, those skilled in the art are understanding under the prerequisite of spirit of the present invention, can carry out corresponding conversion to the present invention according to the prior art and the knowledge in present technique field, these technical schemes all fall within the scope of the present invention.
Embodiment 1: the preparation of celphere
Getting the microcrystalline Cellulose 400g of 80 sieves, and placed centrifugal one-step palletizing coating pan, is binding agent with 475ml water, the setting engine speed is 330r/min, and the spray pump rotating speed is 25r/min, and the jet pressure of spray gun is 0.15MPa, jet flow is 12L/min, carries out centrifugal granulator.After binding agent added, rolling 1min was continued on the chassis, formed microcrystalline Cellulose nuclear core particle.60 ℃ of dryings 2 hours.
Exsiccant microcrystalline Cellulose nuclear core particle is crossed 26 mesh sieves, get the nuclear core particle of lower part of screen branch and cross 35 mesh sieves, obtain the nuclear core particle of particle diameter between 610 μ m～750 μ m orders, weigh, calculating average one-tenth ball rate is 61.8% (n=10).
Embodiment 2: ball core spraying medicine-feeding
Metformin hydrochloride 250g
Hydroxypropyl emthylcellulose 20cps 10g
Pulvis Talci 25g
Water 800ml
Preparation process: get metformin hydrochloride 250g, hydroxypropyl emthylcellulose 5g adds entry 800ml, and the slight fever dissolving slowly adds the 25g Pulvis Talci before the coating under stirring, stirs into suspension.The celphere 110g that gets embodiment 1 preparation places fluid bed one-step palletizing coating pan, and setting inlet temperature and be 60 ℃, air pressure is that 0.35bar, atomizing pressure are that 1.5bar, hydrojet speed are 7.5g/min.With the above-mentioned medicinal liquid coating of adding medicine under stirring, coating finishes the back and continued dry 2 minutes.Weigh, calculating the medicine-feeding rate is 94.5%, and the piller degree of adhesion is 3.4%.
The amount of the amount-binding agent of medicine-feeding rate %=[(micropill gross weight-celphere)/dosage] * 100%.
Micropill gross weight * 100% behind degree of adhesion=(micropill gross weight behind the coating-not the weight of adhesion micropill)/coating
Embodiment 3: ball core spraying medicine-feeding
Metformin hydrochloride 250g
Hydroxypropyl emthylcellulose 6cps 10g
Pulvis Talci 25g
Water 800ml
Preparation process: get metformin hydrochloride 250g, hydroxypropyl emthylcellulose 10g adds entry 800ml, and the slight fever dissolving slowly adds the 25g Pulvis Talci before the coating under stirring, stirs into suspension.The 110g that gets embodiment 1 preparation places fluid bed one-step palletizing coating pan, and setting inlet temperature and be 60 ℃, air pressure is that 0.35bar, atomizing pressure are that 1.5bar, hydrojet speed are 7.5g/min.With the above-mentioned medicinal liquid coating of adding medicine under stirring, coating finishes the back and continued dry 2 minutes.Weigh, the method for pressing among the embodiment 2 is calculated medicine-feeding rate and degree of adhesion, and the medicine-feeding rate is 97.6%, and the piller degree of adhesion is 2.1%.
Embodiment 4: ball core spraying medicine-feeding
Metformin hydrochloride 250g
Hydroxypropyl emthylcellulose 50cps 5g
Pulvis Talci 25g
Water 800ml
Preparation process: get metformin hydrochloride 250g, hydroxypropyl emthylcellulose 15g adds entry 800ml, and the slight fever dissolving slowly adds the 25g Pulvis Talci before the coating under stirring, stirs into suspension.The celphere 110g that gets embodiment 1 preparation places miniature coating pan, and setting kettle temperature is that 60 ℃, pot rotating speeds are 30rpm, and with the speed of the 4.0g/min coating of adding medicine to, coating is rotated further 10 minutes dryings after finishing with above-mentioned medicinal liquid.Weigh, the method for pressing among the embodiment 2 is calculated medicine-feeding rate and degree of adhesion, and the medicine-feeding rate is 94.1%, and the piller degree of adhesion is 4.8%.
Embodiment 5: ball core spraying medicine-feeding
Metformin hydrochloride 250g
Hydroxypropyl emthylcellulose 20g
Pulvis Talci 25g
Water 800ml
Preparation process: get metformin hydrochloride 250g, hydroxypropyl emthylcellulose 20g adds entry 800ml, and the slight fever dissolving slowly adds the 25g Pulvis Talci before the coating under stirring, stirs into suspension.The celphere 110g that gets embodiment 1 preparation places fluid bed one-step palletizing coating pan, and setting inlet temperature and be 60 ℃, air pressure is that 0.35bar, atomizing pressure are that 1.5bar, hydrojet speed are 7.5g/min.With the above-mentioned medicinal liquid coating of adding medicine under stirring, coating finishes the back and continued dry 2 minutes.Weigh, the method for pressing among the embodiment 2 is calculated medicine-feeding rate and degree of adhesion, and the medicine-feeding rate is 97.5%, and the piller degree of adhesion is 2.3%.
Embodiment 6: the enteric coating of medicine carrying micropill
Medicine carrying micropill 200g
Youteqi L100-55 40g
Macrogol 4000 4g
Pulvis Talci 8g
Ethanol 500ml
Preparation process: take by weighing 40g Youteqi L100-55, the 4g Macrogol 4000 adds ethanol 500ml, standing over night, dissolving.Slowly add the 8g Pulvis Talci before the coating, stir into suspension.The medicine carrying micropill 200g that gets by prepared among the embodiment 3 places fluid bed one-step palletizing coating pan, and setting inlet temperature and be 40 ℃, air pressure is that 0.35bar, atomizing pressure are that 1.5bar, hydrojet speed are 2.5g/min.Above-mentioned medicinal liquid is carried out enteric coating under stirring, in the coating process, adjust inlet temperature at any time and make kettle temperature remain on 35 ℃.After the end, material continued fluidisation 10 minutes, weigh, and weightening finish 20%, the piller degree of adhesion is 2.7%.According to drug release determination method (Chinese Pharmacopoeia version in 2000 two appendix X D second method (1)), adopt dissolution method first subtraction unit, be solvent with 0.1mol/L hydrochloric acid 750ml, rotating speed is that per minute 100 changes, operation in accordance with the law.In the time of 120 minutes, get solution 10ml and filter, as surveying solution (1) fully.The 0.2mol/L sodium radio-phosphate,P-32 solution 250ml that adds 37 ℃ then, mixing is 6.8 ± 0.05 with the pH value of 2mol/L hydrochloric acid solution or 2mol/L sodium hydroxide solution regulator solution, continues stripping 45 minutes, gets solution 10mL and filters, as surveying solution (2) fully.Precision is measured and is surveyed solution (1) 1ml fully, put in the 10ml measuring bottle, add the pH6.8 phosphate buffer to scale, shake up, as need testing solution (1), according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), wavelength place at 233nm measures trap, by the absorptance (E1%1cm) of C4H11N5HCL is 798 to calculate burst size in the acid. precision is measured and is surveyed solution (2) 1ml fully, put in the 50ml measuring bottle, add the pH6.8 phosphate buffer and be diluted to scale, shake up. according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), measuring trap at the wavelength place of 233nm, is 798 to calculate the burst size in buffer by the absorptance (E1%1cm) of C4H11N5HCL.After measured, burst size 99.69% in 17.48%, 45 minute alkali of burst size in the acid in 2 hours.
Embodiment 7: the enteric coating of medicine carrying micropill
Medicine carrying micropill 200g
Youteqi L100-55 46g
Macrogol 4000 4.6g
Pulvis Talci 9.2g
Ethanol 580ml
Preparation process: take by weighing 46g Youteqi L100-55, the 4.6g Macrogol 4000 adds ethanol 580ml, standing over night, dissolving.Slowly add the 9.2g Pulvis Talci before the coating, stir into suspension.The medicine carrying micropill 200g that gets by prepared among the embodiment 3 places fluid bed one-step palletizing coating pan, and setting inlet temperature and be 40 ℃, air pressure is that 0.35bar, atomizing pressure are that 1.5bar, hydrojet speed are 2.5g/min.Above-mentioned medicinal liquid is carried out enteric coating under stirring, in the coating process, adjust inlet temperature at any time and make kettle temperature remain on 35 ℃.After the end, material continued fluidisation 10 minutes, weigh, and weightening finish 23%, the piller degree of adhesion is 2.5%.According to the method among the embodiment 6, sample is carried out drug release determination.Burst size 99.84% in 12.33%, 45 minute alkali of burst size in the acid in 2 hours.
Embodiment 8: the enteric coating of medicine carrying micropill
Medicine carrying micropill 200g
Youteqi L100-55 50g
Triethyl citrate 5g
Pulvis Talci 10g
Ethanol 625ml
Preparation process: take by weighing 50g Youteqi L100-55, the 5g Macrogol 4000 adds ethanol 625ml, standing over night, dissolving.Slowly add the 10g Pulvis Talci before the coating, stir into suspension.The medicine carrying micropill 200g that gets by prepared among the embodiment 3 places fluid bed one-step palletizing coating pan, and setting inlet temperature and be 40 ℃, air pressure is that 0.35bar, atomizing pressure are that 1.5bar, hydrojet speed are 2.5g/min.Above-mentioned medicinal liquid is carried out enteric coating under stirring, in the coating process, adjust inlet temperature at any time and make kettle temperature remain on 35 ℃.After the end, material continued fluidisation 10 minutes, weigh, and weightening finish 25%, the piller degree of adhesion is 2.8%.According to the method among the embodiment 6, sample is carried out drug release determination.Burst size 99.80% in 9.81%, 45 minute alkali of burst size in the acid in 2 hours.
Embodiment 9: the enteric coating of medicine carrying micropill
Medicine carrying micropill 200g
Youteqi L100-55 54g
Macrogol 4000 5.4g
Pulvis Talci 10.8g
Ethanol 675ml
Preparation process: take by weighing 54g Youteqi L100-55,5.4g Macrogol 4000, add ethanol 675ml, standing over night, dissolving. slowly add the 10.8g Pulvis Talci before the coating, stirring into suspension. the medicine carrying micropill 200g that gets by prepared among the embodiment 3 places fluid bed one-step palletizing coating pan, setting inlet temperature is 40 ℃, air pressure is 0.35bar, atomizing pressure is 1.5bar, hydrojet speed is that 2.5g/min. carries out enteric coating with above-mentioned medicinal liquid under stirring, in the coating process, at any time adjusting inlet temperature makes kettle temperature remain on 35 ℃. after the end, material continued fluidisation 10 minutes, weigh, weightening finish 27%, the piller degree of adhesion is that 2.9%. is according to the method among the embodiment 6, sample is carried out in the drug release determination .2 hour acid burst size 99.25%. in 1.20%, 45 minute alkali of burst size
Embodiment 10: the enteric coating of medicine carrying micropill
Medicine carrying micropill 200g
Youteqi L100-55 60g
Macrogol 4000 6g
Pulvis Talci 12g
Ethanol 750ml
Preparation process: take by weighing 60g Youteqi L100-55, the 6g Macrogol 4000 adds ethanol 750ml, standing over night, dissolving.Slowly add the 12g Pulvis Talci before the coating, stir into suspension.The medicine carrying micropill 200g that gets by prepared among the embodiment 3 places fluid bed one-step palletizing coating pan, and setting inlet temperature and be 40 ℃, air pressure is that 0.35bar, atomizing pressure are that 1.5bar, hydrojet speed are 2.5g/min.Above-mentioned medicinal liquid is carried out enteric coating under stirring, in the coating process, adjust inlet temperature at any time and make kettle temperature remain on 35 ℃.After the end, material continued fluidisation 10 minutes, weigh, and weightening finish 30%, the piller degree of adhesion is 4.4%.According to the method among the embodiment 6, sample is carried out drug release determination.Burst size 99.37% in 1.04%, 45 minute alkali of burst size in the acid in 2 hours.
The test of embodiment 11 technology repeatability
Prescription and technology according to embodiment 9, carried out the preparation of 4 batches of metformin hydrochloride enteric-coated pellet capsules again, and investigated their fundamental property and quality, the every index basically identical of four batch samples, illustrate that this prescription and technology have repeatability preferably, see table 1 for details.
The prescription of the metformin hydrochloride enteric-coated pellet capsule of table 1 and technology reproducible test results
Claims (17)
1. a pharmaceutical composition for the treatment of diabetes contains a. celphere; B. biguanides antidiabetic medicine active component layer, this active component layer is coated on the outside of celphere; C. enteric coating layer, this enteric coating layer is coated on the outside of biguanides antidiabetic medicine active component layer, described enteric coating layer contains high molecular polymer and plasticizer, wherein high molecular polymer is selected from Youteqi L100-55, diethyl phthalate, Youteqi RL100, Youteqi RS100 or their mixture, plasticizer is selected from Polyethylene Glycol, triethyl citrate or their mixture, described biguanides antidiabetic medicine active component layer contains active medicine and binding agent, and binding agent is selected from hydroxypropyl emthylcellulose, hydroxypropyl emthylcellulose acetic acid succinate, polyvinylpyrrolidone, ethyl cellulose, hydroxyethyl-cellulose, hydroxyethylmethyl-cellulose, hydroxypropyl cellulose or their mixture.
2. according to the pharmaceutical composition of claim 1, wherein said high molecular polymer is selected from Youteqi L100-55.
3. according to the pharmaceutical composition of claim 1, described plasticizer is selected from Macrogol 4000.
4. according to the pharmaceutical composition of claim 1, active medicine wherein is selected from metformin hydrochloride.
5. according to the pharmaceutical composition of claim 1, binding agent wherein is a hydroxypropyl emthylcellulose.
6. according to the pharmaceutical composition of each claim in the claim 1～5, celphere wherein is microcrystalline Cellulose ball, sugar pill or starch ball.
7. according to the pharmaceutical composition of claim 6, celphere wherein is the microcrystalline Cellulose ball.
8. according to the pharmaceutical composition of claim 7, wherein the particle diameter of microcrystalline Cellulose ball is 610 μ m～750 μ m.
9. according to the pharmaceutical composition of claim 1, consisting of wherein to the coating solution of ball core spraying medicine-feeding:
Metformin hydrochloride 250g
Hydroxypropyl emthylcellulose 20cps 10g
Pulvis Talci 25g
Water 800ml.
10. according to the pharmaceutical composition of claim 1, consisting of wherein to the coating solution of ball core spraying medicine-feeding:
Metformin hydrochloride 250g
Hydroxypropyl emthylcellulose 6cps 10g
Pulvis Talci 25g
Water 800ml.
11. according to the pharmaceutical composition of claim 1, consisting of wherein to the coating solution of ball core spraying medicine-feeding:
Metformin hydrochloride 250g
Hydroxypropyl emthylcellulose 50cps 5g
Pulvis Talci 25g
Water 800ml.
12. according to the pharmaceutical composition of claim 1, consisting of wherein to the coating solution of ball core spraying medicine-feeding:
Metformin hydrochloride 250g
Hydroxypropyl emthylcellulose 20g
Pulvis Talci 25g
Water 800ml.
13. according to the pharmaceutical composition of claim 10, consisting of wherein with respect to the coating solution of 200g medicine carrying micropill enteric coating:
Youteqi L100-55 40g
Macrogol 4000 4g
Pulvis Talci 8g
Ethanol 500ml.
14. according to the pharmaceutical composition of claim 10, consisting of wherein with respect to the coating solution of 200g medicine carrying micropill enteric coating:
Youteqi L100-55 46g
Macrogol 4000 4.6g
Pulvis Talci 9.2g
Ethanol 580ml.
15. according to the pharmaceutical composition of claim 10, consisting of wherein with respect to the coating solution of 200g medicine carrying micropill enteric coating:
Youteqi L100-55 50g
Triethyl citrate 5g
Pulvis Talci 10g
Ethanol 625ml.
16. according to the pharmaceutical composition of claim 10, consisting of wherein with respect to the coating solution of 200g medicine carrying micropill enteric coating:
Youteqi L100-55 54g
Macrogol 4000 5.4g
Pulvis Talci 10.8g
Ethanol 675ml
17. according to the pharmaceutical composition of claim 10, consisting of wherein with respect to the coating solution of 200g medicine carrying micropill enteric coating:
Youteqi L100-55 60g
Macrogol 4000 6g
Pulvis Talci 12g
Ethanol 750ml.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1413582A (en) * | 2002-11-29 | 2003-04-30 | 贵州圣济堂制药有限公司 | Dimethyldiguanide hydrochloride enteric solubility tablet and its preparation method |
| CN1561980A (en) * | 2004-03-26 | 2005-01-12 | 贵州圣济堂制药有限公司 | Melbine hydrochloride enteric coatel slow-releasing preparation and its preparing method |
-
2006
- 2006-11-20 CN CN200610145832A patent/CN101190179B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1413582A (en) * | 2002-11-29 | 2003-04-30 | 贵州圣济堂制药有限公司 | Dimethyldiguanide hydrochloride enteric solubility tablet and its preparation method |
| CN1561980A (en) * | 2004-03-26 | 2005-01-12 | 贵州圣济堂制药有限公司 | Melbine hydrochloride enteric coatel slow-releasing preparation and its preparing method |
Non-Patent Citations (4)
| Title |
|---|
| 于少云等.微丸的进展.中国新药杂志8 12.1999,8(12),802-806. |
| 于少云等.微丸的进展.中国新药杂志8 12.1999,8(12),802-806. * |
| 阳长明.缓释与控释小丸的研究进展.华西药学杂志16 2.2001,16(2),121-123. |
| 阳长明.缓释与控释小丸的研究进展.华西药学杂志16 2.2001,16(2),121-123. * |
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