CN100512834C - Orally administered formulation of eight ingredients-containing 'Xi Lei San' and its colon target oral formulation and preparation method - Google Patents
Orally administered formulation of eight ingredients-containing 'Xi Lei San' and its colon target oral formulation and preparation method Download PDFInfo
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Abstract
The invention provides an orally administered formulation of eight ingredients-containing 'Xi Lei San' and its colon target oral formulation and preparation method by changing enema administration into oral administration large intestine targeted treatment, the medicinal preparation can increase the focus medicinal concentration, improve adaptability for the patients, reduce stomach and intestine stimulation, thus improve treating effects.
Description
Technical field
The present invention relates to a kind of eight flavor XILEI SAN oral formulations and colon-targeted orally-administered preparation and preparation methoies.
Background technology
Ulcerative colitis is common clinical, frequently-occurring disease, is one of generally acknowledged refractory disease of World Health Organization (WHO).Because of its course of disease is longer, touching difficulty heals, and has a strong impact on patient's quality of life and physical and mental health.It is reported that 30 years old-60 years old crowd's prevalence is 1-1.5 ‰, and along with the raising of people's living standard, dietary structure changes, China's ulcerative colitis sickness rate is the trend of obvious rising.
At present, still do not have the specific drug of treatment ulcerative colitis clinically, clinical Western medicine generally needs long-term prescription based on aminosallcylic acid, corticoid class medicine, easily recurrence after the drug withdrawal, and toxic and side effects is many.Chinese medicine has better curative effect to this disease, especially be administered for treatment ulcerative colitis determined curative effect with eight flavor XILEI SAN coloclysis, but use inconvenience, need the administration of medical worker's coloclysis during treatment, time-consuming, expensive, bothersome, painful, the patient is often because of being difficult to adhere to therapy discontinued.Therefore, press for a kind of advantage that had both had both oral administration and coloclysis administration clinically, can reduce medicine again to the gastrointestinal zest, reducing effective ingredient destroys and loss at gastrointestinal, preserve effective ingredient to greatest extent, thereby guarantee giving full play to of curative effect of medication, and taking convenience, the medicine that can increase patient's compliance comes out.
(the oral colon-specific drug delivery system of oral colon positioning feed system, OCDDS) be the purpose that reaches conlon targeting release by oral, when treatment colon local disease, can avoid drug-induced systemic side effects, be the clinical treatment colonic diseases effectively, route of administration easily, can improve the focus drug level, improve patient's compliance, give full play to drug effect.So OCDDS not only has the important clinical meaning, vast market prospect is arranged also.Extract oral colon targeting drug administration preparation technical difficulty is bigger, and domestic this type of research report is not at present seldom seen this type of launch yet.
Summary of the invention
An object of the present invention is to provide eight flavor XILEI SAN oral formulations and colon-targeted orally-administered preparations thereof,, give full play to drug effect, conveniently take to improve patient's compliance.
Another object of the present invention has provided the preparation method of eight flavor XILEI SAN oral formulations.
Eight flavor XILEI SAN are recorded in ministry standard the 12 (WS3-B-2273) and are made up of Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing).We adopt multiple cold and cool product can dispel intravital intrinsic heat, and simultaneously, Borneolum Syntheticum, watermelon crystal, Margarita etc. have virus killing, antibacterial action, and Borax has astriction in addition, thereby reaches heat-clearing and toxic substances removing, the effect of reducing swelling and alleviating pain.
Eight flavor XILEI SAN have curative effect preferably to ulcerative colitis, medicine of the present invention discharges at colon, can avoid gastrointestinal that the destruction and the minimizing medicine of medicine are stimulated gastrointestinal, significantly improve medicine in the partial concentration of focus, reduce toxic and side effects, give full play to curative effect of medication, and patient's taking convenience, avoid the hardship of coloclysis administration.Simultaneously, clinical a kind of determined curative effect, the new medicine medicine easy to use of providing is provided in the present invention.
According to our medicine characteristics, utilize gastrointestinal tract mucous pH raise gradually and colon have the characteristics of enzyme-specific, adopt various coating materials, two kinds of material coatings of dissolved enteric material and polysaccharide under specific pH.Coating material of the present invention can be following or other coating material: chitosan Chitosan, also claim chitosan, and formal name used at school is β-1,4-gathers-glucamine; Chitin Chitin has another name called chitin, chitin, chitin, molecular formula and molecular weight: (C8H13N05) n (203.19) n; No. 2 resins of homemade acrylic acid, No. 3 resins of homemade acrylic acid, Eudragit RS, Eudragit L, Eudragit S, PVAP, CAP, HPMCCAS, all be recorded in 297 pages and 153 pages, 154 pages of People's Health Publisher's February in 2002 the 4th edition " practical drug preparation technique ".Acrylic resin modification series of products Eudragit RS, Eudragit L and Eudragit S, Eudragit RL100 that Germany R0hm Pharma company produces can be as coating materials of the present invention.For example just to be to use methacrylic acid and acrylic acid methyl ester. mol ratio be the copolymer of 1: 1 or 1: 2 for EudragitL or Eudragit S.Press list of references: the resin EudragitL/S that " Ishibashi T; Pitcairn GR; Yoshino H; et al.Scintigraphic evaluation of a newcapsule-type colon specific drug delivery system in health volunteers.J PharmSci; 1998; 87 (5): 531. " provides is an anionoid type chemical compound, carboxyl in its structure does not dissociate under low pH condition, so do not dissolve under one's belt, after entering small intestinal, along with the raising of pH, the molecule generation ionizing of polymer and gradually the dissolving.Intramolecular carboxyl ratio is big more, and dissolved pH is high more.Therefore by adjusting the purpose that coating composition and control clothing layer thickness can reach colon administration.Because intestinal pH is subjected to the difference fluctuation range of factors such as diet, disease, individuality bigger, thereby the locating effect of this type of medicine-releasing system produced certain influence, occur the phenomenon of not disintegrate sometimes.In order to overcome its shortcoming, wrap with the pectin clothing on the surface of medicament pellet, the pectin clothing decomposes under the effect of the proprietary enzyme of colon again, and they are according to different release principles, resist of the influence of gastrointestinal tract various factors jointly, thereby guarantee the colon positioning release function of this preparation coated preparation.
Medicine of the present invention adopts main component in HPLC, the GC method mensuration side on the basis of original standard, main medicine in the TLC method discriminating side, and the limit standard of formulation heavy metal, can effectively control product quality, guarantee curative effect of medication, thereby improved the Chinese medicine quality standard.
Outstanding advantage of the present invention shows: (1) eight flavor XILEI SAN oral formulations of the present invention and colon-targeted orally-administered preparation thereof are preserved effective ingredient to greatest extent, thereby guarantee giving full play to of curative effect of medication, and change oral way into, taking convenience, can increase patient's compliance, the eight flavor XILEI SAN powders that its commercial value is used far above traditional enema treatment.(2) colon-targeted orally-administered preparation particularly, the advantage that had both had both oral administration and coloclysis administration, can reduce medicine again to the gastrointestinal zest, reducing effective ingredient destroys and loss at gastrointestinal, preserve effective ingredient to greatest extent, its effect experiment shows that the eight flavor XILEI SAN powders that effect and enema treatment use are similar, is higher than not eight flavor XILEI SAN oral formulations of the non-targeting of coating, thereby has guaranteed giving full play to of curative effect of medication.(3) the common oral formulations of eight flavor XILEI SAN of the present invention, even coating not, suitable therapeutic effect is also arranged, though effect slightly is weaker than eight flavor XILEI SAN coloclysis powders, but it is very inconvenient at the powder coloclysis, under the puzzlement of influence treatment, allow doctor and patient that the treatment choice of oral taking convenience is arranged, relative colon-targeted orally-administered preparation, the technology and the equipment requirements of the oral formulations that eight flavor XILEI SAN are common are simple, and the production cost of medical manufacturing enterprise is low, and is comprehensive, its practicality and commercial value far surpass the weak slightly deficiency of curative effect, and be also very valuable.
The prescription of eight flavor XILEI SAN oral formulations of the present invention and colon-targeted orally-administered preparation thereof is formed: Indigo Naturalis 1-15 part, Calculus Bovis 1-5 part, Margarita (bean curd is processed) 1-5 part, Borneolum Syntheticum 1-5 part, watermelon crystal 1-5 part, Mirabilitum crystallina 1-10 part, Borax 1-5 part, Sal Ammoniacus (processing) 1-5 part.
Its better formula is:
12 parts of Indigo Naturaliss, 2 parts of Calculus Boviss, 6 parts of Margaritas (bean curd is processed), 1 part of Borneolum Syntheticum, 4 parts of watermelon crystals, 6 parts of Mirabilitum crystallinas, 4 parts of Boraxs, 4 parts of Sal Ammoniacuss (processing).
Instructions of taking of the present invention:
The corresponding weight per package that getting embodiment 1 provides is eight flavor XILEI SAN common oral granular formulations of 0.5 gram, by every day 3 times, takes two bags at every turn, and 5 days is a course of treatment.
The corresponding weight per package that getting embodiment 1 provides is eight flavor XILEI SAN colon-targeted orally-administered granules of 0.5 gram, by every day 3 times, takes a bag at every turn, and 5 days is a course of treatment.
Corresponding every weight that getting embodiment 2 provides is eight flavor XILEI SAN common oral capsules of 0.3 gram, by every day 3 times, takes two bags at every turn, and 5 days is a course of treatment.
Corresponding every weight that getting embodiment 2 provides is eight flavor XILEI SAN colon-targeted orally-administered capsule preparations of 0.3 gram, by every day 3 times, takes a bag at every turn, and 5 days is a course of treatment.
The technical specification and the economic indicator of eight flavor XILEI SAN oral formulations and colon-targeted orally-administered preparation thereof and former eight flavor stannum quasi-tradition powders are compared as follows:
Technical specification and economic indicator are relatively
| Title | Traditional powder of eight flavor XILEI SAN | Eight flavor XILEI SAN oral formulations and colon-targeted orally-administered preparations thereof |
| Dosage form | Powder, technology falls behind, and zest is big, takes inconvenience. | Coating, the local drug concentration height, zest is little, taking convenience. |
| Administering mode | Coloclysis | Oral |
| Method for making | Pulverize, make powder. | Pulverizing, coating, filled hard capsules or make granule, tablet, soft capsule. |
| Quality standard | TLC differentiates Borneolum Syntheticum, Indigo Naturalis, no content assaying method. | GC surveys content of bornyl alcohol, HPLC measures the Calculus Bovis content of bilirubin, and TLC differentiates Borneolum Syntheticum, Indigo Naturalis. |
| The market share | 5% | 10-30% |
| Production capacity | 8,000,000 boxes | 2,000 ten thousand boxes |
| Every day drug cost | 7 yuan/day | 5 yuan/day |
Below further set forth the beneficial effect of medicine of the present invention by testing example, these test the routine pharmacodynamics test that has comprised medicine of the present invention and pharmacology, toxicology test.
1 pharmacodynamic study part
The comparative tests research of eight flavor XILEI SAN different approaches drug treatment rat ulcer colitis
Materials and methods
1 animal and grouping: 8 (Nat'l Pharmaceutical ﹠ Biological Products Control Institute's Experimental Animal Center provides) cleanings of new zealand rabbit level, 60 of rats of healthy SD (department of the Chinese Academy of Sciences of Department Of Medicine, Peking University's laboratory animal section provides), male and female half and half, body weight 160 ± 10g, rat is divided into 5 groups of normal group, model group, the eight flavor common treatment groups of XILEI SAN (common group), eight flavor XILEI SAN capsule for treating groups (the colon targeting drug administration group of hard capsule), sulfasalazine matched groups (positive controls), 12 every group at random.
2 main medicine and reagent: eight flavor XILEI SAN (Beijing TongrenTang Co., Ltd); Eight flavor XILEI SAN capsules (Jiangxi book on Chinese herbal medicine work of nature Science and Technology Ltd. provides), sulfasalazine 0.25g/ sheet (Shanghai Sunve Pharmaceutical Co., Ltd.); Ketaject injection (Shanghai No.1 Bio-Chemical Pharmacetical Industry Co., Ltd); CD4, CD8 monoclonal antibody (BD Biosciences company product); CD4, CD8 SABC test kit (SANTA company product); Complete Freund's adjuvant (Sigma company product); TNF-alpha immunization group test kit (Wuhan Boster Biological Technology Co., Ltd.'s product).
3 methods
3.1 modeling method
The preparation of antigen emulsion: get rabbit and separate mucous membrane of colon, add an amount of normal saline and put in the tissue mashing machine and smash to pieces, in-20 ℃ preserve 24 hours down after, molten freezing, again with 4000 rev/mins centrifugal 30 minutes, to get its supernatant be antigen stock and record its protein concentration (14.5g/l).Get antigen stock and equivalent complete Freund's adjuvant mixing is the solution of 10mg/ml, then with syringe aspirate repeatedly, fully emulsified, make the antigen emulsion.
Rat sensitization and processing method: except that normal group, other each group is all given modeling.In rat paw portion, intraperitoneal injection antigen emulsion 1.2ml (containing antigen stock albumen 8mg), conventional raising back the 8th day, subcutaneous in rat back again, intraperitoneal injection antigen stock (not adding complete Freund adjuvant) 0.6ml (containing antigen stock albumen 8mg), anaesthetized with the ketamine intramuscular injection by body weight 2ml/kg in the 14th day, 2% formalin 2ml retention enema 1 hour, the back normal saline flushing, reuse antigen stock 0.6ml coloclysis was kept somewhere 2 hours, normal saline flushing.
3.2 medication after modeling the 1st day, eight flavor common treatment groups of XILEI SAN and hard capsule treatment treated animal are irritated stomach respectively and are given 0.1g (0.1g/ml) eight flavor XILEI SAN, positive control treated animal coloclysis gives sulfasalazine 100mg (100mg/ml), every day 1 time, totally 18 days.Normal group and model group animal give isometric normal saline and irritate stomach.
3.3 handle and observe each treated animal administration after 18 days, pluck eyeball and get blood, take off vertebra and put to death, upwards separate colon 6～8cm from anus 2cm place rapidly, cut off along the mesentery longitudinal axis, clean with normal saline flushing, and intestinal mucosa upwards is tiled on the stencil plate fixing, a situation arises to observe inflammation and ulcer; Carry out colon's damage scoring, standards of grading (seeing Table) according to the inflammation damnification degree; Clip part colon, 10% formalin solution is fixed, pathological section, HE dyeing, light microscopic is observed ulcer down and is generated situation; Part colon preserves in liquid nitrogen rapidly, is ready to use in the expression that SABC is measured CD3, CD4, CD8 and TNF-α.
Table one: colon's morphology standards of grading
4.3 flow cytometry is surveyed CD4, CD8T lymphocyte level: rat eye is got blood, adds anticoagulant heparin, it is even to get in the centrifuge tube of blood 50ul and 5ul CD4 monoclonal antibody and 5ulCD8 monoclonal antibody shake respectively, 4 ℃ of preservation 30min down; Add an amount of blood cytolysate, 1000 rev/mins of centrifugal 1.5min abandon its supernatant; Add an amount of normal saline with 1000 rev/mins, centrifugal 1.5min repeatedly several times, loses redness degree of being with the test tube bottom, filters back up flow type cell instrument and detects.
4.4 immunohistochemistry detects: with the tissue freezing section that preserves in the liquid nitrogen, do SABC to specifications.
5 statistical methods utilization SPSS11.5 software carries out statistical procedures.Hemocyte and immunohistochemistry result adopt variance analysis, the pathological tissue employing rank test of keeping the score.
The result
1. general form is learned and is observed and colon's damage scoring
The hyperemia of visible model group serous coat, edema, lymphocytic infiltration, vessel wall thickening under the common light microscopic, intestinal mucosa strips off, and forms bigger and a fairly large number of ulcer, and muscular layer of mucosa destroys, visible mucosa erosion, tissue necrosis.Each treatment group ulcer number and area reduce than model group, rotten to the corn, inflammatory cell infiltration degree alleviates, especially obvious with colon targeting drug administration group and positive controls, except that above-mentioned symptom is alleviated, the colon targeting drug administration treated animal is also shown in ulcer bottom Submucosa the fibrous connective tissue hypertrophy, accompany a small amount of inflammatory cell infiltration, Mild edema.Its colon's damage scoring (seeing Table two A), model group is marked all than normal group significantly higher (P＜0.01); Each group of treatment obviously reduces than model group, and significant difference (P＜0.05-0.01) is arranged; Colon scoring shows that colon targeting drug administration group treatment treated animal is lower than common group (P＜0.05), and colon targeting drug administration group and positive controls do not have significant difference (P〉0.05); Common group of damage scoring is higher than positive controls (P＜0.01)), prompting eight flavor XILEI SAN colon targeting drug administration group therapeutical effect and effect are similar to sulfasalazine, but are better than common group of treatment of eight flavor XILEI SAN.
Table two A: colon's damage scoring
Annotate: compare * P＜0.01 with the normal group group; With coloclysis matched group △ P＜0.01; Compare ※ P＜0.01 with positive controls; With common group of comparison ※ ※ P＜0.01.
2. flow cytometry is measured peripheral blood CD3, CD4, CD8T lymphocyte level (seeing Table two B) model group CD4T lymphocyte level than normal group obviously raise (P＜0.01), the CD8T lymphocyte level then significantly reduces (P＜0.01), and CD4/CD8 is significantly rising (P＜0.01) then.Experimental result shows that model group exists CD4, CD8T lymphocyte unusual, and eight flavor XILEI SAN and sulfasalazine all have regulating action to periphery blood T lymphocyte, and the oral colon-target capsule is obvious than ordinary preparation, and effect and sulfasalazine are similar.
Table two B: rat peripheral blood CD3, CD4, CD8T lymphocyte be (%, x ± s) relatively
4. respectively organize rat colon mucosa-immune group testing result through immunohistochemical staining, as developer, what they showed in section is the xanchromatic fine and close point-like of palm fibre with DAB, and the fine and close point of visible pale brown color is positioned on the after birth or the endochylema place under the high power lens.CD3, CD4, CD8T lymphocyte and TNF-α positive cell all have expression in the intestinal mucosa between lamina propria and mucosal epithelium, but mainly are arranged in the solid layer of intestinal mucosa.With the image analyzer counting, 6 zones are got in every section, in all cells of being caught of so basic assurance all are collected in, and avoid repeat count.Carry out Flame Image Process with Qwin100 software, measurement result (seeing Table three).
4.1 CD3, CD4, CD8T lymphocyte and TNF-alpha immunization group result
Model group and normal group compare, and CD3T, cd4 t cell level significantly descend (P＜0.01), and the cd8 t cell level raises and significant difference (P＜0.05) is arranged.Experimental result shows that model group rat colon mucosa exists CD3T, CD4, CD8T lymphocyte unusual, eight flavor XILEI SAN capsules (oral colon-target administration) are aspect adjusting CD4, CD8T lymphocyte level, effect is better than eight flavor XILEI SAN, and similar to sulfasalazine effect and effect.
And TNF-α positive cell is at the expression of rat colon mucosa, then be, model group descends than model group than normal group rising, each treatment group all has significant difference (P＜0.01) experimental result to show, eight flavor XILEI SAN hard capsules (oral colon-target administration) are better than eight flavor XILEI SAN on adjusting TNF-alpha levels, and similar to sulfasalazine effect and effect.
Table three colonic mucosa CD4, CD8, TNF-α positive cell are relatively
Eight flavor XILEI SAN capsules (oral colon-target administration) are heightened the CD8T lymphocyte at peripheral blood, are reduced CD4/CD8 ratio; Heighten the expression of CD4T lymphocyte, reduction CD8T lymphocyte and TNF-α in the mucous membrane of colon part, and colon damage scoring aspect all is better than eight flavor XILEI SAN, illustrate that eight flavor XILEI SAN colon topical treatment ulcerative colitiss obviously are better than oral administration, the colon topical can promote the useful effect composition promptly to disengage, play antiinflammatory action, the part medicine in the medicament can also adhere to the ulcer surface rapidly and play damaging action is again exempted from the protection of local mucous membrane; By the absorption of intestinal, play and adjust immunologic balance in the body on the other hand, and adjust the interior functions such as colony balance of intestinal, thereby play the prophylactic treatment effect of comprehensive integral body effective ingredient.
According to the method that the comparative tests research of the present invention eight flavor XILEI SAN different approaches drug treatment rat ulcer colitis provides, carry out the eight comparative tests researchs of distinguishing the flavor of the various oral colon targeting preparations of XILEI SAN:
The result shows the pharmacodynamics test of capsule (referring to hard capsule), tablet, granule, soft capsule of eight flavor XILEI SAN various oral colon targeting preparations and pharmacological experiment data class seemingly, no significant difference.
Table four: colon's damage scoring
The positive controls of its invading the exterior four is identical with the positive controls that table two A provides, and the hard capsule of table four is exactly the colon targeting drug administration group that provides with table two A; Capsule (referring to hard capsule), tablet, granule, the soft capsule of the various oral formulations of eight flavor XILEI SAN are provided by embodiments of the invention.
2, the oral acute toxicity mice of safety research part LD50 fails to measure, and maximum tolerated dose is equivalent to 4800 times of dose.Subacute toxicity test is the result show: 30 times, 60 times and 120 times of doses give the WISTAR rat respectively, continuous 9 months, the animal ordinary circumstance was good, and body weight gain is consistent with matched group, blood cell and biochemical indicator are normal, and pathological change is not seen in each internal organs morphology of animal yet.The result confirms: eight flavor XILEI SAN belong to actual innocuous substance, and recommended dose is safe.
3, colon targeting preparation colon drug release behavior is observed.
γ-scintigraphy shows: medicine does not discharge at stomach, duodenum, discharges fully at colonic.
Specific embodiment:
Embodiment 1, the eight flavor common oral granular formulations of XILEI SAN and eight flavor XILEI SAN oral colon-target granules.
Among the preparation technology, suitable illumination, temperature, humidity are controlled at respectively: 150-300LX; Humidity: 45-65%; Temperature: 18-26 ℃.
Prescription is formed: Indigo Naturalis 18g, Calculus Bovis 2.4g, Margarita (bean curd is processed) 9g, Borneolum Syntheticum 1.5g, watermelon crystal 6g, Mirabilitum crystallina 9g, Borax 6g, Sal Ammoniacus (processing) 6g; Preparation method: (1), get Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing) drying for standby in proportion; Be 30 minutes drying time; Baking temperature is controlled at 75 ℃; (2), with pulverizing medicinal materials after the drying, adopt ball mill to pulverize, or adopt micronizing, standby; (3), grain forming, can adopt high-speed stirred granulation or fluidized bed granulation method to granulate; With HPMC is binding agent, and consumption is 4%; With MCC, L-HPC is disintegrating agent, and consumption respectively is 3%, 4%, and temperature is controlled at 30 ℃; Rotating speed is 80 commentaries on classics, and the time is 5 minutes, drying, and granulate gets granule; Obtain the common oral granular formulation of eight flavor XILEI SAN.
Append the following step again for obtaining eight flavor XILEI SAN oral colon-target granules:
(4), coating; get (3) grain forming thing coating; press the percentage by weight of grain forming thing and select coating material: EudragitL/S1%, starch 2%, Eudragit RL100 1% and pectin 2%; coating material adds an amount of 70% alcohol solvent dissolving; adopt coating pelletizing mechanism to be equipped with micropill; or the employing fluidized bed coating, obtain eight flavor XILEI SAN oral colon-target granules.
Embodiment 2, the eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules.
Among the preparation technology, suitable illumination, temperature, humidity are controlled at respectively: 150-300LX; Humidity: 45-65%; Temperature: 18-26 ℃; The used wetting agent of this technology is the aqueous solution of polyvinylpyrrolidone, and wherein the weight proportion of polyvinylpyrrolidone aqueous solution is polyvinylpyrrolidone: water=1:20;
Prescription is formed: Indigo Naturalis 18g, Calculus Bovis 2.4g, Margarita (bean curd is processed) 9g, Borneolum Syntheticum 1.5g, watermelon crystal 6g, Mirabilitum crystallina 9g, Borax 6g, Sal Ammoniacus (processing) 6g; Enteric coated capsule preparation method: (1), get Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing) drying for standby in proportion; Be 25 minutes drying time; Baking temperature is controlled at 75 ℃; (2), with pulverizing medicinal materials after the drying, adopt ball mill to pulverize, or adopt micronizing, standby; (3), micropill molding: (31) are earlier minced xeraphium and are added wetting agent and make soft material, total consumption of wetting agent and xeraphium weight such as mince wherein, sieving granulates is rolled onto bead back the adding in the coating pan, spray the female ball of wetting agent moistening again, add then xeraphium mince roll coated, repeatable operation, meet the requirements until most of micropill particle diameter, take the dish out of the pot, carry out hand sieving with standard screen, the micropill that does not meet the particle diameter requirement is made female ball of next pot time preparation micropill; (32) adopt coating pelletizing mechanism ball, open air blast and air draft, xeraphium is minced directly to add in the coating pan, cover pot cover, open the main frame running, spray into wetting agent, directly molding, the female ball that makes is divided into female ball of different-grain diameter scope at the pill-screening machine top sieve, add in the coating pan respectively, add a cover, the limit spray adds wetting agent, and the limit is for powder, reach requirement until the micropill particle diameter, take the dish out of the pot behind the polishing 5min; Sieve out the micropill that meets the particle diameter requirement with pill-screening machine, the micropill that does not meet the particle diameter requirement is made female ball of next pot time preparation micropill; (33) adopt and to extrude round as a ball comminutor and prepare micropill; Get drying and crushing, the mix homogeneously that sieves adds water and makes soft material in right amount, through squeezing the sieve plate that goes out of aperture 0.8mm, is extruded into the suitable strip of diameter, and advance spheronizator and make granule round as a ball fully, oven dry, the micropill molding is standby; Be prepared into common oral hard capsule or oral colon-target hard capsule respectively according to different needs:
For obtaining eight flavor XILEI SAN common oral hard capsule, with (3) prepared micropill, drying, incapsulate, quality inspection, pack the eight common oral hard capsule of XILEI SAN of distinguishing the flavor of.
Or for obtaining eight flavor XILEI SAN oral colon-target hard capsules, (4), coating, get (3) micropill article shaped coating, press the percentage by weight of micropill article shaped and select coating material: chitosan 4%, Eudragit S 2%, Eudragit L 3% and glucosan 1%, polysaccharide 2%, coating material is with an amount of 70% dissolve with ethanol solution; Adopt coating pelletizing mechanism to be equipped with micropill, or adopt fluidized bed coating; (5), with (4) prepared micropill, drying, incapsulate, quality inspection, pack eight flavor XILEI SAN oral colon-target hard capsules.Polysaccharide can be selected lentinan.
Embodiment 3, the eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules.
Among the preparation technology, suitable illumination, temperature, humidity are controlled at respectively: 150LX; Humidity: 45%; Temperature: 18 ℃; The used wetting agent of this technology is the alcoholic solution of polyvinylpyrrolidone, and wherein the weight proportion of polyvinylpyrrolidone alcoholic solution is polyvinylpyrrolidone: ethanol=1:30;
Prescription is formed: Indigo Naturalis 12g, Calculus Bovis 2g, Margarita (bean curd is processed) 4g, Borneolum Syntheticum 2g, watermelon crystal 3g, Mirabilitum crystallina 6g, Borax 3g, Sal Ammoniacus (processing) 3g; All the other prepare eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules respectively with embodiment 2.Wherein select coating material: Eudragit RS 2%, Eudragit L 3%, Eudragit S 3% and chitin 2%, pectin 1% by the percentage by weight of micropill article shaped for obtaining eight flavor XILEI SAN oral colon-target hard capsules.
Embodiment 4, the eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules.
Among the preparation technology, suitable illumination, temperature, humidity are controlled at respectively: 200LX; Humidity: 50%; Temperature: 20 ℃; The used wetting agent of this technology is the alcoholic solution of polyvinylpyrrolidone, and wherein the weight proportion of polyvinylpyrrolidone alcoholic solution is polyvinylpyrrolidone: ethanol=1:20;
Prescription is formed: Indigo Naturalis 10g, Calculus Bovis 1g, Margarita (bean curd is processed) 2g, Borneolum Syntheticum 4g, watermelon crystal 2g, Mirabilitum crystallina 8g, Borax 2g, Sal Ammoniacus (processing) 2g; All the other prepare eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules respectively with embodiment 2.Wherein select coating material: Eudragit RS 2%, Eudragit L 3%, Eudragit S 3% and chitin 2% by the percentage by weight of micropill article shaped for obtaining eight flavor XILEI SAN oral colon-target hard capsules.
Embodiment 5, the eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules.
Among the preparation technology, suitable illumination, temperature, humidity are controlled at respectively: 300LX; Humidity: 65%; Temperature: 26 ℃; The used wetting agent of this technology is the alcoholic solution of polyvinylpyrrolidone, and wherein the weight proportion of polyvinylpyrrolidone alcoholic solution is polyvinylpyrrolidone: ethanol=1:25;
Prescription is formed: Indigo Naturalis 4g, Calculus Bovis 1g, Margarita (bean curd is processed) 5g, Borneolum Syntheticum 4g, watermelon crystal 3g, Mirabilitum crystallina 6g, Borax 3g, Sal Ammoniacus (processing) 3g; All the other prepare eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules respectively with embodiment 2.Wherein select coating material: Eudragit RS 2%, Eudragit L 3%, Eudragit RL100 1% and chitin 2%, chitosan 1% by the percentage by weight of micropill article shaped for obtaining eight flavor XILEI SAN oral colon-target hard capsules.
Embodiment 6, the eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules.
Select coating material for obtaining eight flavor XILEI SAN oral colon-target hard capsules by the percentage by weight of micropill article shaped: No. 2 resins 2% of homemade acrylic acid, No. 3 resins 3% of homemade acrylic acid and chitin 3%, chitosan 1%.
All the other prepare eight flavor common oral hard capsule of XILEI SAN and eight flavor XILEI SAN oral colon-target hard capsules respectively with embodiment 2.
Embodiment 7, the eight flavor common oral granular formulations of XILEI SAN and eight flavor XILEI SAN oral colon-target granules.
Prescription is formed: Indigo Naturalis 2g, Calculus Bovis 2g, Margarita (bean curd is processed) 3g, Borneolum Syntheticum 2g, watermelon crystal 6g, Mirabilitum crystallina 2g, Borax 6g, Sal Ammoniacus (processing) 6g; Preparation method: (1), get Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing) drying for standby in proportion; Be 30 minutes drying time; Baking temperature is controlled at 75 ℃; (2), with pulverizing medicinal materials after the drying, adopt ball mill to pulverize, or adopt micronizing, standby; (3), grain forming, can adopt high-speed stirred granulation or fluidized bed granulation method to granulate; With HPMC is binding agent, and consumption is 2%; With L-HPC is disintegrating agent, and consumption is 5%, and temperature is controlled at 30 ℃; Rotating speed is 80 commentaries on classics, and the time is 5 minutes, drying, and granulate gets granule; Obtain the common oral granular formulation of eight flavor XILEI SAN.
All the other are with embodiment 1.
Append the following step again for obtaining eight flavor XILEI SAN oral colon-target granules:
(4), coating; get (3) grain forming thing coating, press the percentage by weight of grain forming thing and select coating material: EudragitL/S 4% and carrageenan 1%, adopt coating pelletizing mechanism to be equipped with micropill; or the employing fluidized bed coating, obtain eight flavor XILEI SAN oral colon-target granules.
Embodiment 8, the eight flavor common oral tablets of XILEI SAN and eight flavor XILEI SAN oral colon-target tablets.
Among the preparation technology, suitable illumination, temperature, humidity are controlled at respectively: 240LX; Humidity: 55%; Temperature: 24 ℃.
Prescription is formed: Indigo Naturalis 18g, Calculus Bovis 2.4g, Margarita (bean curd is processed) 9g, Borneolum Syntheticum 1.5g, watermelon crystal 6g, Mirabilitum crystallina 9g, Borax 6g, Sal Ammoniacus (processing) 6g; Preparation method: (1), get Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing) drying for standby in proportion; Be 30 minutes drying time; Baking temperature is controlled at 75 ℃; (2), with pulverizing medicinal materials after the drying, adopt ball mill to pulverize, or adopt micronizing, standby; (3), grain forming, can adopt high-speed stirred granulation or fluidized bed granulation method to granulate; With HPMC is binding agent, and consumption is 4%; With MCC, L-HPC is disintegrating agent, and consumption respectively is 3%, 4%, and temperature is controlled at 30 ℃; Rotating speed is 80 commentaries on classics, and the time is 5 minutes, drying, and granulate, it is stand-by to get granule; Granule is pulverized, and adds 1% Macrogol 4000,2% magnesium stearate, 1% carboxymethyl starch sodium mixing again, tabletting, and slice obtains the common oral tablet of eight flavor XILEI SAN.
Append the following step again for obtaining eight flavor XILEI SAN oral colon-target tablets:
(4), coating; get that the grain forming thing that (3) add Polyethylene Glycol, magnesium stearate, methyl starch sodium is again pulverized, coating again; press the percentage by weight of grain forming thing and select coating material: EudragitL/S1%, starch 2%, EudragitS2% and pectin 1%, PVAP 1%; coating material adds an amount of 85% alcohol solvent dissolving; adopt coating pelletizing mechanism to be equipped with micropill; or the employing fluidized bed coating, obtain eight flavor XILEI SAN oral colon-target tablets.
Embodiment 9, the eight flavor common oral tablets of XILEI SAN and eight flavor XILEI SAN oral colon-target tablets.
Prescription is formed: Indigo Naturalis 10g, Calculus Bovis 2g, Margarita (bean curd is processed) 8g, Borneolum Syntheticum 1g, watermelon crystal 4g, Mirabilitum crystallina 6g, Borax 6g, Sal Ammoniacus (processing) 6g; Preparation method: (1), get Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing) drying for standby in proportion; Be 30 minutes drying time; Baking temperature is controlled at 75 ℃; (2), with pulverizing medicinal materials after the drying, adopt ball mill to pulverize, or adopt micronizing, standby; (3), grain forming, can adopt high-speed stirred granulation or fluidized bed granulation method to granulate; With HPMC is binding agent, and consumption is 4%; With MCC, L-HPC is disintegrating agent, and consumption respectively is 3%, 4%, and temperature is controlled at 30 ℃; Rotating speed is 80 commentaries on classics, and the time is 5 minutes, drying, and granulate, it is stand-by to get granule grain forming thing; The grain forming thing is pulverized, and adds 1% polyethylene glycol 6000,2% magnesium stearate, 1% Pulvis Talci mixing again, tabletting, and slice obtains the common oral tablet of eight flavor XILEI SAN.
Append the following step again for obtaining eight flavor XILEI SAN oral colon-target tablets:
(4), coating; get (3) and add again that Polyethylene Glycol, magnesium stearate, talcous grain forming thing are pulverized, coating again; press the percentage by weight of grain forming thing and select coating material: EudragitL/S1%, starch 2%, Eudragit RL100 1% and pectin 2%; coating material adds an amount of 70% alcohol solvent dissolving; adopt coating pelletizing mechanism to be equipped with micropill; or the employing fluidized bed coating, obtain eight flavor XILEI SAN oral colon-target tablets.
All the other are with embodiment 8.
Embodiment 10, the eight flavor common oral soft capsules of XILEI SAN and eight flavor XILEI SAN oral colon-target soft capsules.
Among the preparation technology, suitable illumination, temperature, humidity are controlled at respectively: 240LX; Humidity: 55%; Temperature: 24 ℃.
Prescription is formed: Indigo Naturalis 18g, Calculus Bovis 2.4g, Margarita (bean curd is processed) 9g, Borneolum Syntheticum 1.5g, watermelon crystal 6g, Mirabilitum crystallina 9g, Borax 6g, Sal Ammoniacus (processing) 6g; Preparation method: (1), get Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing) drying for standby in proportion; Be 30 minutes drying time; Baking temperature is controlled at 75 ℃; (2), with pulverizing medicinal materials after the drying, adopt ball mill to pulverize, or adopt micronizing, solid medicated powder is standby; (3), the soft capsule content prescription is pressed: 60 parts in the solid medicated powder that (2) provide, 10 parts of PEG6000,6 parts of glycerol, 40 parts of vegetable oil, 0.1 part of tween 80,1 part of soybean lecithin, 1 part of oil with hydrogenated soybean; Capsule material formula of soft capsule is pressed: 15 parts in gelatin, 8 parts of arabic gums, 0.01 part of glycerol, 4 parts in syrup, 0.02 part of methyl parahydroxybenzoate, 0.03 part of propyl p-hydroxybenzoate;
Follow these steps to obtain the common oral soft capsule of eight flavor XILEI SAN: (4) add 1 part of tween 80, soybean lecithin with vegetable oil, and 1 part of mix homogeneously of oil with hydrogenated soybean with mulser emulsifying 15min, gets Emulsion; Other gets the glycerol, PEG6000 of formula ratio and the solid medicated powder that (2) provide, and mixing with homogenizer homogenize 40min, adds the Emulsion mix homogeneously again, with homogenizer homogenize 30-60min, promptly gets soft capsule content; (5) get the foregoing thing and obtain the common oral soft capsule of eight flavor XILEI SAN with pressing or dropping preparation method.
Or follow these steps to obtain eight flavor XILEI SAN oral colon-target soft capsules:
(4), the percentage by weight of the solid medicated powder that provides by (2) is selected coating material: EudragitL/S1%, starch 2%, Eudragit RL100 1% and pectin 2%, PVAP1%, HPMCCAS 1%, coating material adds the dissolving of an amount of 70% alcohol solvent, and to obtain coating solution standby, coating solution, vegetable oil are added 1 part of tween 80, soybean lecithin, 1 part of mix homogeneously of oil with hydrogenated soybean, with mulser emulsifying 15min, get Emulsion; Other gets the glycerol, PEG6000 of formula ratio and the solid medicated powder that (2) provide, and mixing with homogenizer homogenize 40min, adds the Emulsion mix homogeneously again, with homogenizer homogenize 50min, promptly gets soft capsule content; (5) get the foregoing thing and obtain eight flavor XILEI SAN oral colon-target soft capsules with pressing or dropping preparation method.
Embodiment 11, the eight flavor common oral soft capsules of XILEI SAN and eight flavor XILEI SAN oral colon-target soft capsules.
Among the preparation technology, suitable illumination, temperature, humidity are controlled at respectively: 240LX; Humidity: 55%; Temperature: 24 ℃.
Prescription is formed: Indigo Naturalis 12g, Calculus Bovis 2g, Margarita (bean curd is processed) 4g, Borneolum Syntheticum 2g, watermelon crystal 3g, Mirabilitum crystallina 6g, Borax 3g, Sal Ammoniacus (processing) 3g; Preparation method: (1), get Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing) drying for standby in proportion; Be 30 minutes drying time; Baking temperature is controlled at 75 ℃; (2), with pulverizing medicinal materials after the drying, adopt ball mill to pulverize, or adopt micronizing, solid medicated powder is standby; (3), the soft capsule content prescription is pressed: 60 parts in the solid medicated powder that (2) provide, 5 parts of PEG6000,4 parts of glycerol, 60 parts of vegetable oil, 0.2 part of tween 80,2 parts of soybean lecithins, 1 part of oil with hydrogenated soybean; Capsule material formula of soft capsule is pressed: 20 parts in gelatin, 8 parts of arabic gums, 0.01 part of glycerol, 4 parts in syrup, 0.04 part of methyl parahydroxybenzoate;
Follow these steps to obtain the common oral soft capsule of eight flavor XILEI SAN: (4) add 1 part of tween 80, soybean lecithin with vegetable oil, and 1 part of mix homogeneously of oil with hydrogenated soybean with mulser emulsifying 15min, gets Emulsion; Other gets the glycerol, PEG6000 of formula ratio and the solid medicated powder that (2) provide, and mixing with homogenizer homogenize 40min, adds the Emulsion mix homogeneously again, with homogenizer homogenize 50min, promptly gets soft capsule content; (5) get the foregoing thing and obtain the common oral soft capsule of eight flavor XILEI SAN with pressing or dropping preparation method.
Or follow these steps to obtain eight flavor XILEI SAN oral colon-target soft capsules:
(4), the percentage by weight of the solid medicated powder that provides by (2) is selected coating material: EudragitL/S3%, starch 2%, Eudragit L 4%, coating material adds the dissolving of an amount of 70% alcohol solvent, and to obtain coating solution standby, coating solution, vegetable oil are added 1 part of tween 80, soybean lecithin, 1 part of mix homogeneously of oil with hydrogenated soybean, with mulser emulsifying 15min, get Emulsion; Other gets the glycerol, PEG6000 of formula ratio and the solid medicated powder that (2) provide, and mixing with homogenizer homogenize 40min, adds the Emulsion mix homogeneously again, with homogenizer homogenize 30-60min, promptly gets soft capsule content; (5) get the foregoing thing and obtain eight flavor XILEI SAN oral colon-target soft capsules with pressing or dropping preparation method.
Embodiment 12, eight flavor XILEI SAN oral colon positioning feed capsule preparations follow these steps to and get:
(1) Indigo Naturalis, Calculus Bovis, Margarita (bean curd is processed), Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, Sal Ammoniacus (processing) drying for standby in proportion in the technology; Be 30 minutes drying time; Baking temperature is controlled at 75 ℃;
(2) with dried pulverizing medicinal materials, standby;
(3) grain forming adopts high-speed stirred granulation or fluidized bed granulation method to granulate; With HPMC is binding agent, and consumption is 5%; With MCC, L-HPC is disintegrating agent, and consumption is respectively 3%, 4%, and temperature is controlled at 30 ℃, and rotating speed is 45 commentaries on classics, and the time is 3 minutes, drying, and granulate gets granule;
(4) micropill molding;
(a) earlier xeraphium is minced and add wetting agent and make soft material, total consumption of wetting agent and xeraphium weight such as mince wherein, sieving granulates is rolled onto bead back the adding in the coating pan, spray the female ball of wetting agent moistening again, add then xeraphium mince roll coated, repeatable operation, meet the requirements until most of micropill particle diameter, take the dish out of the pot, carry out hand sieving with standard screen, the micropill that does not meet the particle diameter requirement is made female ball of next pot time preparation micropill;
(b) adopt coating pelletizing mechanism ball, open air blast and air draft, xeraphium is minced directly to add in the coating pan, cover pot cover, open the main frame running, spray into wetting agent, directly molding, the female ball that makes is divided into female ball of different-grain diameter scope at the pill-screening machine top sieve, add in the coating pan respectively, add a cover, the limit spray adds wetting agent, and the limit is for powder, reach requirement until the micropill particle diameter, take the dish out of the pot behind the polishing 5min; Sieve out the micropill that meets the particle diameter requirement with pill-screening machine, the micropill that does not meet the particle diameter requirement is made female ball of next pot time preparation micropill;
(c) adopt and to extrude round as a ball comminutor and prepare micropill; Get drying and crushing, the mix homogeneously that sieves adds water and makes soft material in right amount, is extruded into the suitable strip of diameter through extruding sieve plate, and advance spheronizator and make granule round as a ball fully, oven dry, it is standby to get the micropill article shaped;
(5) get (4) micropill article shaped coating;
(6) with the micropill of (5) obtained coating, drying incapsulates shell, gets capsule.
All the other are with embodiment 2.
Embodiment 13, organize eight flavor XILEI SAN common oral preparation and many group eight flavor XILEI SAN oral colon targeting preparations more.
It is the oral formulations of being made by the following weight proportion raw material: 1 part of Indigo Naturalis, 5 parts of Calculus Boviss, 1 part of Margarita (bean curd is processed), 5 parts of Borneolum Syntheticums, 1 part of watermelon crystal, 10 parts of Mirabilitum crystallinas, 1 part of Borax, 5 parts of Sal Ammoniacuss (processing).
All the other repeat embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5, embodiment 6, embodiment 6, embodiment 7, embodiment 8, embodiment 9, embodiment 10, embodiment 11, embodiment 12 respectively.
Embodiment 14, organize eight flavor XILEI SAN common oral preparation and many group eight flavor XILEI SAN oral colon targeting preparations more.
It is the oral formulations of being made by the following weight proportion raw material: 15 parts of Indigo Naturaliss, 1 part of Calculus Bovis, 5 parts of Margaritas (bean curd is processed), 1 part of Borneolum Syntheticum, 6 parts of watermelon crystals, 1 part of Mirabilitum crystallina, 5 parts of Boraxs, 1 part of Sal Ammoniacus (processing).
All the other repeat embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5, embodiment 6, embodiment 6, embodiment 7, embodiment 8, embodiment 9, embodiment 10, embodiment 11, embodiment 12 respectively.
Embodiment 15, organize eight flavor XILEI SAN common oral preparation and many group eight flavor XILEI SAN oral colon targeting preparations more.
It is the oral formulations of being made by the following weight proportion raw material: 12 parts of Indigo Naturaliss, 2 parts of Calculus Boviss, 6 parts of Margaritas (bean curd is processed), 1 part of Borneolum Syntheticum, 4 parts of watermelon crystals, 6 parts of Mirabilitum crystallinas, 4 parts of Boraxs, 4 parts of Sal Ammoniacuss (processing).
All the other repeat embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5, embodiment 6, embodiment 6, embodiment 7, embodiment 8, embodiment 9, embodiment 10, embodiment 11, embodiment 12 respectively.
Embodiment 16, organize eight flavor XILEI SAN oral colon targeting preparations more.
Replace Eudragit L with No. 2 resins of homemade acrylic acid; No. 3 resins of homemade acrylic acid replace Eudragit S.All the other repeat embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5, embodiment 6, embodiment 6, embodiment 7, embodiment 8, embodiment 9, embodiment 10, embodiment 11, embodiment 12 respectively.
Claims (1)
1, a kind of preparation method of eight flavor XILEI SAN colon-targeted orally-administered preparations follows these steps to and get: among the preparation technology, the illumination that suits, temperature, humidity are controlled at respectively: 150-300LX; Humidity: 45-65%; Temperature: 18-26 ℃; Prescription is formed: Indigo Naturalis 18g, Calculus Bovis 2.4g, bean curd are processed Margarita 9g, Borneolum Syntheticum 1.5g, watermelon crystal 6g, Mirabilitum crystallina 9g, Borax 6g, are processed Sal Ammoniacus 6g; Preparation method: (1), get Indigo Naturalis, Calculus Bovis, bean curd and process Margarita, Borneolum Syntheticum, watermelon crystal, Mirabilitum crystallina, Borax, process Sal Ammoniacus drying for standby in proportion; Be 30 minutes drying time; Baking temperature is controlled at 75 ℃; (2), with pulverizing medicinal materials after the drying, adopt ball mill to pulverize, or adopt micronizing, standby; (3), grain forming, can adopt high-speed stirred granulation or fluidized bed granulation method to granulate; With HPMC is binding agent, and consumption is 4%; With MCC, L-HPC is disintegrating agent, and consumption respectively is 3%, 4%, and temperature is controlled at 30 ℃; Rotating speed is 80 commentaries on classics, and the time is 5 minutes, drying, and granulate gets granule; It is characterized in that appending again the following step: (4), coating; get (3) grain forming thing coating; press the percentage by weight of grain forming thing and select coating material: EudragitL/S 1%, starch 2%, Eudragit RL100 1% and pectin 2%; coating material adds an amount of 70% alcohol solvent dissolving; adopt coating pelletizing mechanism to be equipped with micropill; or the employing fluidized bed coating, obtain the granule of eight flavor XILEI SAN colon-targeted orally-administered preparations.
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| EP3741368A4 (en) * | 2018-01-18 | 2021-12-22 | Keio University | Capsule for treating ulcerative colitis |
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Non-Patent Citations (5)
| Title |
|---|
| 中华人民共和国***药典委员会. 中华人民共和国***药典委员会，编.中华人民共和国*** 药品标准 中药成方制剂. 1997 |
| 中华人民共和国***药典委员会. 中华人民共和国***药典委员会，编.中华人民共和国*** 药品标准 中药成方制剂. 1997 * |
| 中华人民共和国***药品标准 中药成方制剂 第十二册. 中华人民共和国***药典委员会编，3，中华人民共和国***药典委员会. 1997 中药药剂学. 张兆旺，509，中国中医药出版社. 2003 |
| 中华人民共和国***药品标准 中药成方制剂 第十二册. 中华人民共和国***药典委员会编，3，中华人民共和国***药典委员会. 1997 * |
| 中药药剂学. 张兆旺，509，中国中医药出版社. 2003 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP3741368A4 (en) * | 2018-01-18 | 2021-12-22 | Keio University | Capsule for treating ulcerative colitis |
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