CN1781477A - Composite capsule for stomach intestine and its preparing method and use - Google Patents
Composite capsule for stomach intestine and its preparing method and use Download PDFInfo
- Publication number
- CN1781477A CN1781477A CNA2004100548493A CN200410054849A CN1781477A CN 1781477 A CN1781477 A CN 1781477A CN A2004100548493 A CNA2004100548493 A CN A2004100548493A CN 200410054849 A CN200410054849 A CN 200410054849A CN 1781477 A CN1781477 A CN 1781477A
- Authority
- CN
- China
- Prior art keywords
- capsule
- medicine
- enteric
- medicated cap
- enteric coated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 239000002775 capsule Substances 0.000 title claims abstract description 153
- 210000002784 stomach Anatomy 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims description 8
- 210000000936 intestine Anatomy 0.000 title abstract 5
- 239000002131 composite material Substances 0.000 title abstract 3
- 230000002496 gastric effect Effects 0.000 claims abstract description 68
- 239000003814 drug Substances 0.000 claims abstract description 66
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 229920002472 Starch Polymers 0.000 claims description 38
- 235000019698 starch Nutrition 0.000 claims description 38
- 239000008107 starch Substances 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 30
- 239000003292 glue Substances 0.000 claims description 19
- 230000000968 intestinal effect Effects 0.000 claims description 18
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- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 claims description 16
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
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Images
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- Medicinal Preparation (AREA)
Abstract
The present invention relates to medicine and its production process, and the composite gastrointestinal capsule is one kind of oral medicine preparation with both stomach releasing medicine component and intestine releasing medicine component. The composite gastrointestinal capsule includes one capsule cap capable of being dissolved inside stomach and holding stomach releasing medicine component, and one capsule body cap capable of being dissolved inside intestine and holding intestine releasing medicine component. The medicine preparation features no mutual action between different medicine components, raised compound medicine preparation stability, located medicine releasing, reduced stimulation on stomach and intestine of some medicine, synergistic medicine action and accurate medicine content.
Description
One,
Technical field
The present invention relates to a kind of gastrointestinal complex type capsules and its production and application.Discharge medicine respectively in gastric and intestinal behind this capsule oral, this capsule is made up of stomach dissolution type capsule medicated cap and enteric coated capsule.
Two,
Background technology
Oral Pharmaceutical dosage forms is a lot of at present, comprise tablet, capsule, oral liquid, pill, Emulsion etc., but it is single at stomach or at intestinal mostly that it discharges the medicine position, have following shortcoming: 1. single-point release medicine can increase the weight of stomach or intestinal injury, for example dosage is 10mg, and the threshold dose of gastrointestinal side effect is 5mg, if according to traditional dosage form administration, will inevitably increase incidence rate of adverse reaction; 2. conventional dosage forms blood concentration fluctuation scope is bigger, and the medicine peak concentration may cause poisoning; 3. drug treating time is short, and medicining times is many; 4. administration time is difficult to determine in the compound preparation, and for example glipizide requires administration 30 minutes ante cibum, and when metformin hydrochloride requires to have meal or the back administration of having meal, when administration more rationally is the insoluble problem of conventional formulation to the two compound preparation.5. according to traditional method, the physical and chemical properties of drugs instability, or be easy to take place interactional medicine and be difficult to make compound preparation; 6. owing to the interaction between the compound medicine, EDD may shorten.7. traditional compound preparation introduces many troubles for the quality control of preparation because several drugs mixes existence.
There are some complex capsule dosage forms at present, as multilamellar capsule for medicine (patent No. CN 2614676Y); Cellular-type medicament capsule (patent No. CN 2423892Y); Huweidan capsule (patent No. CN 2506254Y); Complex capsule (patent No. CN 2601094Y).Multilamellar capsule, Huweidan capsule, complex capsule all belong to large capsule the inside cover Caplet, the capsule volume is bigger, and capsule space drug loading reduces, and patient is difficult to take, and all do not adopt capsule gastrointestinal packaging technique, can't realize that medicine discharges respectively respectively in gastric and intestinal.Though cellular-type medicament capsule capsule volume is less, can't use capsule gastrointestinal packaging technique, can't realize that medicine discharges respectively respectively in gastric and intestinal.
Three,
Summary of the invention
The present invention is a kind of gastrointestinal complex type capsules, it is characterized in that comprising that capsule medicated cap and the enteric solubility capsule made by the stomach dissolution type material form.
Stomach dissolution type capsule medicated cap is made up of the stomach dissolution type material, and it is selected from gelatin, a kind of or its mixture of animal glue or other protein component.The enteric solubility capsule is made up of the enteric solubility material, and it is selected from Lac; the cellulose acetate phthalate ester; crylic acid resin (as Eudragit L and S type etc.); the polyvinyl acetate phthalic acid ester; phthalic acid hypromellose ester; succinic acid acetic acid hydroxypropyl methylcellulose; and plasticizer is (as diethyl phthalate; poly-ethanol; propylene glycol; glycerol triacetate; dimethyl phthalate; dibutyl sebacate; triethyl citrate; tributyl citrate; CitroflexA-2; the acetylated monoglycerides of Oleum Ricini and percentage; glycerol; dimethyl phthalate; diethyl phthalate; phthalic acid dibutyl ester; triethyl citrate; tributyl citrate; the acetyl group tributyl citrate; acetyl group tributyl citrate etc.) with porogen (as the PEG class; PVP; sucrose; salt) a kind of or its mixture such as.Capsule material can also add various coloring agent and lucifuge agent (titanium dioxide etc.).
Capsular preparation method, comprise following steps: 1. prepare gastric solubleness capsule medicated cap and enteric coated capsule, 2. mechanical fill medicine, master operation comprises the supply of enteric coated capsule, enteric glue shell is arranged, calibrating direction, enteric glue shell separates, and the enteric medicine is filled, 3. enteric glue shell closure, 4. secondary is filled in the gastric solubleness capsule medicated cap of pastille, and closure is sent.The closure of enteric coated capsule and gastric solubleness capsule medicated cap can adopt methods such as groove type is sealed, the sealing of gelatin band, heated sealant, chemical seal.Can fill in gastric solubleness capsule medicated cap and the enteric coated capsule with a kind of medicine or compound medicine or available excipient of various pharmaceutics and adjuvant, discharge at stomach and intestinal respectively.Wherein can pack in gastric solubleness capsule medicated cap and the enteric coated capsule solid particle, tablet, capsule, drop pill, micropill or liquid preparation, explosive payload is less than 500mg.
The medicine of being adorned in the stomach dissolution type capsule medicated cap is: glipizide, gliclazide, glimepiride, glibenclamide, gliquidone, repaglinide, rosiglitazone, pioglitazone, acarbose, voglibose, simvastatin, atorvastatin, rosuvastatin, enalapril, lisinopril, benazepril, losartan, irbesartan, Radix Salviae Miltiorrhizae drop pill, LIUWEI DIHUANG WAN, hypericin, Charantin.Wherein can also use multiple excipient and adjuvant etc. in the gastric solubleness capsule medicated cap, described excipient and accessory package are starch-containing, the compositions of one or more materials of solubility/insoluble salt, octadecanol, stearic acid, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, citric acid and the sodium sulfite etc. of microcrystalline Cellulose, inorganic salts, hydroxypropyl emthylcellulose, ethyl cellulose, polyacrylic resin class, polycarboxy ethene, alginic acid.
The medicine of being adorned in the enteric coated capsule is: aspirin, acetaminophen, indomethacin, sulindac, naproxen, diclofenac, nabumetone, loxoprofen, nimesulide, piroxicam, meloxicam, plug Lay former times cloth, rofecoxib, ibuprofen, tetracycline, doxycycline, erythromycin, erythromycin ethylsuccinate, Roxithromycin, azithromycin, clarithromycin, meleumycin, midecamycin, acetylspiramycin, metronidazole, methotrexate, 6-dredges basic purine, 5-fluorouracil, thyroliberin, glucocorticoid, metformin, reserpine, phentolamine, tolbutamide, caffeine, thyroxine, aminophylline, estrogen, captopril, vitamin.Wherein can also use multiple excipient and adjuvant etc. in the enteric coated capsule, described excipient and accessory package are starch-containing, the compositions of one or more materials of solubility/insoluble salt, octadecanol, stearic acid, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, citric acid and the sodium sulfite etc. of microcrystalline Cellulose, inorganic salts, hydroxypropyl emthylcellulose, ethyl cellulose, polyacrylic resin class, polycarboxy ethene, alginic acid.
Gastrointestinal complex type capsules release in vivo can be undertaken by following mechanism:
A) release, the hydrolysis under the acidity effect of gastric juice of gastric solubility capsule medicated cap, the capsule medicated cap destroys, and drug release is to gastric.The enteric solubility capsule does not dissolve in the sour environment of gastric juice, hydrolysis under the alkalescence effect of intestinal juice, and capsule dissolves, drug release is in intestinal.
B) transhipment, the medicine that gastric discharges be emptied to intestinal very soon, and enteric solubility capsule halves volume ratio is bigger because granule is smaller, and it is slow to be emptied to the intestinal time, approximately postpones 30 minutes～1 hour.
C) absorption and pharmacological action, the medicine that gastric discharges are in the very fast absorption of harmonization of the stomach small intestinal, and the drug absorption that discharges in the intestinal is slower.The absorption peak of two kinds of medicines separates, and makes the pharmacological action gentleness.After Fig. 1 represents to take the gastrointestinal complex type capsules, pharmacodynamics effect intensity (as: blood pressure, blood glucose etc.); After Fig. 2 represents to take general capsule, pharmacodynamics effect intensity (as: blood pressure, blood glucose etc.).Gastrointestinal complex type capsules pharmacological action gentleness, prolongation action time, toxic and side effects reduce as seen from the figure.
The advantage of comparing the gastrointestinal complex type capsules with traditional oral formulations is: 1. reduce injury of gastrointestinal tract, medicine is discharged respectively in stomach and intestinal, both reached the clinical pharmacology effect, not causing again the gastrointestinal untoward reaction has increased compliance of patients; 2. owing to, the blood concentration fluctuation scope is reduced drug absorption time that gastric discharges and the drug absorption time phase difference that in intestinal, discharges 30 minutes～1 hour; 3. the drug absorption time lengthening has certain slowly releasing effect, reduces patient's medicining times; The compound medicine administration time is more rationalized, and the medicine that gastric discharges arrived intestinal in 30 minutes～1 hour in advance than the medicine that discharges in the intestinal; 5. utilize the said preparation means the unsettled medicine of physicochemical property can be made compound preparation; 6. can prolong drug effect duration, reduce because the drug failure that interacts and cause between the compound medicine.
The design of capsule body: production enteric solubility capsule medicated cap, make bayonet socket in capsule medicated cap inboard; Production enteric solubility capsule body is made bayonet socket respectively at the capsule body two ends; Production gastric solubility capsule medicated cap is made bayonet socket in capsule medicated cap inboard.Press prior art production enteric solubility capsule, and then the capsule medicated cap of gastric solubility is stuck in the end of enteric solubility capsule body.See Fig. 3
After obtaining gastric solubleness capsule medicated cap and enteric coated capsule, fill medicine, carry out mechanical fill, master operation comprises the supply of enteric coated capsule, enteric glue shell is arranged, calibrating direction, enteric glue shell separates, and the enteric medicine is filled, enteric glue shell closure, the enteric coated capsule secondary is filled in the gastric solubleness capsule medicated cap of pastille, and closure is sent.Wherein the closure of enteric coated capsule and gastric solubleness capsule medicated cap can adopt methods such as groove type is sealed, the sealing of gelatin band, heated sealant, chemical seal.Generally can adopt the lock ditch registration technology of traditional capsule medicated cap and utricule, the lock ditch of capsule medicated cap and utricule is coincide mutually, thereby guarantee that utricule and capsule medicated cap seal reliably, the depth of lock ditch can be adjusted as required.In order further to guarantee the stable of preparation, can use the sealing of gelatin band, or capsule medicated cap and utricule be merged, or use low plait point liquid, by chemical reaction sealed bladder medicated cap and utricule in the junction.Concrete commercial production operating process sketch is seen Fig. 4.
This kind preparation is convenient to quality control because two kinds of active medicines are filled in respectively in gastric solubleness capsule medicated cap and the enteric coated capsule, makes the analyzing and testing of two kinds of medicines simpler, accurately.
Four,
Description of drawings
Fig. 1, take the blood glucose drop-out value behind the gastrointestinal complex type capsules;
Fig. 2, take the blood glucose drop-out value behind the general capsule;
Fig. 3, capsule designs technology;
Fig. 4, novel capsule industry production design;
The structural representation of Fig. 5, novel gastroenteritic complex type capsules.Among the figure: 1, enteric solubility capsule; 2, enteric solubility capsule; 3, the medicine that discharges in the intestinal; 4, the medicine of gastric release; 5, gastric solubility capsule;
Fig. 6, novel Radix Salviae Miltiorrhizae drop pill aspirin capsule;
Fig. 7, novel glipizide metformin capsule;
Fig. 8, the release profiles of novel compound metformin gastroenteritic compound capsule in gastric juice and intestinal juice;
The release in vitro curve of Fig. 9, common diformin tablet;
The external stripping curve of Figure 10, novel compound aspirin gastroenteritic compound capsule;
The external stripping curve of Figure 11, common aspirin phenacetin caffeine;
Figure 12, the external stripping curve of novel compound dipyridamole complex capsule;
Figure 13, the external stripping curve of common dipyridamole.
Five,
The specific embodiment
Embodiment 1 gastrointestinal complex type capsules preparation method 1
Stomach dissolution type capsule medicated cap: application gelatin, titanium dioxide, coloring agent are material, and heat is melted back reverse mould drying in particular mold and formed.
The enteric solubility utricule: using gelatin is that main material prepares conventional capsule, and the preparation enteric coating liquid carries out coating, and concrete coating solution prescription is as follows:
Each 2 parts of acrylic resin II number and acroleic acid resin III numbers, Oleum Ricini 2g, diethyl phthalate 2g, Tween 80 2g, 95% ethanol adds to 100ml.
Production technology: gastric-dissolved capsule is being dipped in enteric coating liquid one time again after becoming mould on the mould, carry out the demoulding, otch, fit, the enteric solubility Capsules.
After obtaining above-mentioned stomach dissolution type capsule medicated cap and enteric solubility utricule, machinery fill medicine, master operation comprises the supply of enteric coated capsule, and enteric glue shell is arranged, calibrating direction, enteric glue shell separates, the enteric medicine is filled, enteric glue shell closure, and secondary is filled in the gastric solubleness capsule medicated cap of pastille, with groove type locking mode closure, send.
Embodiment 2 gastrointestinal complex type capsules preparation methoies 2
Enteric coated capsule is prepared as follows: take by weighing 1 part on acrylic resin L type, 10 parts of pharmagels, 30 parts of distilled water, be mixed with the water solublity glue, add 1%～2% diethyl phthalate, 1%PVP, behind 0.5% pigment, dip in glue with special capsule mould and once make basic capsule, after the drying, capsule dip in again outward get one time 8% enteric solubility acrylic resin aqueous solution promptly.
After obtaining above-mentioned stomach dissolution type capsule medicated cap and enteric solubility utricule, machinery fill medicine, master operation comprises the supply of enteric coated capsule, and enteric glue shell is arranged, calibrating direction, enteric glue shell separates, the enteric medicine is filled, enteric glue shell closure, and secondary is filled in the gastric solubleness capsule medicated cap of pastille, with groove type locking mode closure, send.
Embodiment 3 Radix Salviae Miltiorrhizae drop pill aspirin gastrointestinal complex type capsules.
Prescription is formed:
6 of gastric solubility part Radix Salviae Miltiorrhizae drop pills
Enteric solubility part aspirin 75mg
Starch 75mg
Differential silica gel 2%
Production technology is got aspirin and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
External stripping curve: with reference to figure 6:
The composition of prescription:
Gastric solubility part glipizide 2.5mg
Sodium lauryl sulphate 1%
Starch 45mg
Micropowder silica gel 2%
Production technology is got glipizide and sodium lauryl sulphate and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP aqueous solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Enteric coated capsule part metformin hydrochloride 250mg
Starch 50mg
Micropowder silica gel 2%
Production technology is got metformin hydrochloride and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP aqueous solution, adopts wet granulation technology, granulates, and fill promptly got fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
With reference to figure 7:
External stripping curve: with reference to figure 8, Fig. 9.
Embodiment 5 compound recipes isosorbide mononitrate/aspirin gastrointestinal complex type capsules.
Prescription is formed:
Gastric solubleness part isosorbide mononitrate 20mg
Starch 30mg
Micropowder silica gel 2%
Production technology is got isosorbide mononitrate and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, and wet granulation technology is granulated, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Enteric solubility part aspirin 75mg
Starch 75mg
Differential silica gel 2%
Production technology is got aspirin and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Stripping curve: with reference to Figure 10, Figure 11.
Embodiment 6 compound recipe dipyridamole gastrointestinal complex type capsules
Prescription is formed:
Gastric solubleness part dipyridamole 25mg
Starch 25mg
Differential silica gel 2%
Production technology is got dipyridamole and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, and wet granulation technology is granulated, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Enteric solubility part aspirin 75mg
Starch 75mg
Differential silica gel 2%
Production technology is got aspirin and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Stripping curve: with reference to Figure 12, Figure 13.
Embodiment 7 aspirin dextropropoxyphene napsilate gastrointestinal complex type capsules.
Prescription is formed:
Gastric solubleness part dextropropoxyphene napsilate 50mg
Starch 25mg
Differential silica gel 2%
Production technology is got LOMAR PWA EINECS 246-676-2 Dextropoxypheene and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, and wet granulation technology is granulated, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Enteric solubility part aspirin 75mg
Starch 75mg
Differential silica gel 2%
Production technology is got aspirin and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Embodiment 8 codeine phosphates and aspirin gastrointestinal complex type capsules.
Prescription is formed:
Gastric solubleness part codeine phosphate 5mg
Starch 45mg
Differential silica gel 2%
Production technology is got codeine phosphate and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, and wet granulation technology is granulated, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Enteric solubility part aspirin 75mg
Starch 75mg
Differential silica gel 2%
Production technology is got aspirin and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Embodiment 9 rosiglitazone metformin hydrochloride gastrointestinal complex type capsules.
The composition of prescription:
Gastric solubility part rosiglitazone 2.5mg
Starch 45mg
Micropowder silica gel 2%
Production technology is got rosiglitazone and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Enteric coated capsule part metformin hydrochloride 250mg
Starch 50mg
Micropowder silica gel 2%
Production technology is got metformin hydrochloride and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP aqueous solution, adopts wet granulation technology, granulates, and fill promptly got fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Embodiment 10 glimepiride metformin hydrochloride gastrointestinal complex type capsules.
The composition of prescription:
Gastric solubility part glimepiride 1mg
Sodium lauryl sulphate 1%
Starch 49mg
Micropowder silica gel 2%
Production technology is got glimepiride and sodium lauryl sulphate and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP aqueous solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Enteric coated capsule part metformin hydrochloride 250mg
Starch 50mg
Micropowder silica gel 2%
Production technology is got metformin hydrochloride and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP aqueous solution, adopts wet granulation technology, granulates, and fill promptly got fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Embodiment 11 simvastatin aspirin gastrointestinal complex type capsules.
Prescription is formed:
Gastric solubleness part simvastatin 10mg
Starch 40mg
Differential silica gel 2%
Production technology is got simvastatin and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, and wet granulation technology is granulated, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Enteric solubility part aspirin 75mg
Starch 75mg
Differential silica gel 2%
Production technology is got aspirin and starch and is adopted equivalent to progressively increase behind the dilution method mix homogeneously, is binding agent with the 5%PVP alcoholic solution, adopts wet granulation technology, granulates, and fill promptly after the dry back of 40 degree added the micropowder silica gel mixings.
Claims (12)
1. gastrointestinal complex type capsules is characterized in that comprising that capsule medicated cap and the enteric solubility capsule made by the stomach dissolution type material form.
2. according to the capsule described in the claim 1, it is characterized in that described stomach dissolution type capsule medicated cap is made up of the stomach dissolution type material, it is selected from a kind of of gelatin, animal glue or other protein component or its mixture.
3. according to the capsule described in the claim 1; it is characterized in that described enteric solubility capsule is made up of the enteric solubility material, it is selected from Lac; the cellulose acetate phthalate ester; crylic acid resin (as Eudragit L and S type etc.); the polyvinyl acetate phthalic acid ester; phthalic acid hypromellose ester; succinic acid acetic acid hydroxypropyl methylcellulose; and plasticizer is (as diethyl phthalate; Polyethylene Glycol; propylene glycol; glycerol triacetate; dimethyl phthalate; dibutyl sebacate; triethyl citrate; tributyl citrate; CitroflexA-2; the acetylated monoglycerides of Oleum Ricini and percentage; glycerol; dimethyl phthalate; diethyl phthalate; phthalic acid dibutyl ester; triethyl citrate; tributyl citrate; the acetyl group tributyl citrate; acetyl group tributyl citrate etc.) with porogen (as the PEG class; PVP; sucrose; salt) a kind of or its mixture such as.
4. according to claim 2,3 described stomach dissolution type capsule medicated cap and enteric coated capsulees, it is characterized in that capsule material can also add various coloring agent and lucifuge agent (titanium dioxide etc.).
5. the described capsular preparation method of claim 1～4, comprise following steps: 1. prepare gastric solubleness capsule medicated cap and enteric coated capsule, 2. mechanical fill medicine, master operation comprises the supply of enteric coated capsule, enteric glue shell is arranged, calibrating direction, enteric glue shell separates, and the enteric medicine is filled, 3. enteric glue shell closure, 4. secondary is filled in the gastric solubleness capsule medicated cap of pastille, and closure is sent.
6. capsular preparation method according to claim 5 is characterized in that wherein the closure of enteric coated capsule and gastric solubleness capsule medicated cap can adopt methods such as groove type is sealed, the sealing of gelatin band, heated sealant, chemical seal.
7. the described capsule of claim 1～6 is characterized in that can filling in gastric solubleness capsule medicated cap and the enteric coated capsule with a kind of medicine or compound medicine or available excipient of various pharmaceutics and adjuvant, discharges at stomach and intestinal respectively.
8. according to gastric solubleness capsule medicated cap and the enteric coated capsule described in the claim 7, it is characterized in that can pack in gastric solubleness capsule medicated cap and the enteric coated capsule solid particle, tablet, capsule, drop pill, micropill or liquid preparation, explosive payload is less than 500mg.
9. capsule according to claim 7 is characterized in that the medicine of packing in the gastric solubleness capsule medicated cap is: glipizide, gliclazide, glimepiride, glibenclamide, gliquidone, repaglinide, rosiglitazone, pioglitazone, acarbose, voglibose, simvastatin, atorvastatin, rosuvastatin, enalapril, lisinopril, benazepril, losartan, irbesartan, codeine, Radix Salviae Miltiorrhizae drop pill, LIUWEI DIHUANG WAN, hypericin, Charantin.
10. capsule according to claim 7, it is characterized in that can also using multiple excipient and adjuvant etc. in the gastric solubleness capsule medicated cap, described excipient and accessory package are starch-containing, the compositions of one or more materials of solubility/insoluble salt, octadecanol, stearic acid, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, citric acid and the sodium sulfite etc. of microcrystalline Cellulose, inorganic salts, hydroxypropyl emthylcellulose, ethyl cellulose, polyacrylic resin class, polycarboxy ethene, alginic acid.
11. enteric coated capsule according to claim 7 is characterized in that the medicine that enteric coated capsule is packed into is: aspirin, acetaminophen, indomethacin, sulindac, naproxen, diclofenac, nabumetone, loxoprofen, nimesulide, piroxicam, meloxicam, plug Lay former times cloth, rofecoxib, ibuprofen, tetracycline, doxycycline, erythromycin, erythromycin ethylsuccinate, Roxithromycin, azithromycin, clarithromycin, meleumycin, midecamycin, acetylspiramycin, metronidazole, methotrexate, 6-dredges basic purine, 5-fluorouracil, thyroliberin, glucocorticoid, metformin, reserpine, phentolamine, tolbutamide, caffeine, thyroxine, aminophylline, estrogen, captopril, vitamin.
12. capsule according to claim 7, it is characterized in that can also using multiple excipient and adjuvant etc. in the enteric coated capsule, described excipient and accessory package are starch-containing, the compositions of one or more materials of solubility/insoluble salt, octadecanol, stearic acid, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, citric acid and the sodium sulfite etc. of microcrystalline Cellulose, inorganic salts, hydroxypropyl emthylcellulose, ethyl cellulose, polyacrylic resin class, polycarboxy ethene, alginic acid.
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| CNB2004100548493A CN100400036C (en) | 2004-07-27 | 2004-07-27 | Composite capsule for stomach intestine and its preparing method and use |
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|---|---|---|---|
| CNB2004100548493A CN100400036C (en) | 2004-07-27 | 2004-07-27 | Composite capsule for stomach intestine and its preparing method and use |
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| CN1781477A true CN1781477A (en) | 2006-06-07 |
| CN100400036C CN100400036C (en) | 2008-07-09 |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102274191A (en) * | 2011-06-10 | 2011-12-14 | 浙江丽水众益药业有限公司 | Coating liquid composition of erythromycin enteric-coated pellet |
| CN102349887A (en) * | 2011-08-02 | 2012-02-15 | 天津市嵩锐医药科技有限公司 | Diclofenac sodium acetaminophen gastrointestinal type capsule medicinal composition |
| CN104302278A (en) * | 2012-03-29 | 2015-01-21 | 塞拉拜姆有限责任公司 | Gastrointestinal site-specific oral vaccination formulations active on the ileum and appendix |
| CN104758180A (en) * | 2014-01-06 | 2015-07-08 | 山东诚创医药技术开发有限公司 | Secondary filling method for compound preparation capsules |
| US9907755B2 (en) | 2013-03-14 | 2018-03-06 | Therabiome, Llc | Targeted gastrointestinal tract delivery of probiotic organisms and/or therapeutic agents |
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|---|---|---|---|---|
| US7163693B1 (en) * | 1999-07-30 | 2007-01-16 | Smithkline Beecham Plc | Multi-component pharmaceutical dosage form |
| CN2423892Y (en) * | 2000-04-30 | 2001-03-21 | 尹为民 | Isolating medicinal capsule |
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| CN102274191A (en) * | 2011-06-10 | 2011-12-14 | 浙江丽水众益药业有限公司 | Coating liquid composition of erythromycin enteric-coated pellet |
| CN102349887A (en) * | 2011-08-02 | 2012-02-15 | 天津市嵩锐医药科技有限公司 | Diclofenac sodium acetaminophen gastrointestinal type capsule medicinal composition |
| CN104302278A (en) * | 2012-03-29 | 2015-01-21 | 塞拉拜姆有限责任公司 | Gastrointestinal site-specific oral vaccination formulations active on the ileum and appendix |
| CN109172816A (en) * | 2012-03-29 | 2019-01-11 | 塞拉拜姆有限责任公司 | The active stomach and intestine locus specificity Oral vaccination preparation on ileum and appendix |
| US10588857B2 (en) | 2012-03-29 | 2020-03-17 | Therabiome, Llc | Gastrointestinal site-specific oral vaccination formulations active on the ileum and appendix |
| US10369111B2 (en) | 2013-03-14 | 2019-08-06 | Therabiome, Llc | Targeted gastrointestinal tract delivery of probiotic organisms and/or therapeutic agents |
| US9907755B2 (en) | 2013-03-14 | 2018-03-06 | Therabiome, Llc | Targeted gastrointestinal tract delivery of probiotic organisms and/or therapeutic agents |
| US11590083B2 (en) | 2013-03-14 | 2023-02-28 | Therabiome, Llc | Targeted gastrointestinal tract delivery of probiotic organisms and/or therapeutic agents |
| CN104758180A (en) * | 2014-01-06 | 2015-07-08 | 山东诚创医药技术开发有限公司 | Secondary filling method for compound preparation capsules |
| CN109247906A (en) * | 2017-07-12 | 2019-01-22 | 卡普索影像公司 | For controlling the capsule enteric coating layer of balloon expandable time started |
| CN108078988B (en) * | 2018-02-13 | 2019-10-25 | 山西省太原晋阳制药厂 | C14H10Cl2NNaO2 and the compound sustained-released composition of codeine phosphate and preparation method thereof |
| CN108078988A (en) * | 2018-02-13 | 2018-05-29 | 山西省太原晋阳制药厂 | C14H10Cl2NNaO2 and the compound sustained-released composition of codeine phosphate and preparation method thereof |
| CN112679624A (en) * | 2021-03-18 | 2021-04-20 | 华南理工大学 | Polysaccharide derivative and life nutrition capsule using same |
| CN112679624B (en) * | 2021-03-18 | 2021-07-20 | 华南理工大学 | Life nutrition capsule |
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