CN108201531A - Segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium and preparation method thereof - Google Patents
Segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium and preparation method thereof Download PDFInfo
- Publication number
- CN108201531A CN108201531A CN201611173969.4A CN201611173969A CN108201531A CN 108201531 A CN108201531 A CN 108201531A CN 201611173969 A CN201611173969 A CN 201611173969A CN 108201531 A CN108201531 A CN 108201531A
- Authority
- CN
- China
- Prior art keywords
- starch
- capsule
- sulbenicillin sodium
- colon
- coating
- 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.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides segmented intestine targeted starch capsules of a kind of highly dissoluble sulbenicillin sodium and preparation method thereof, using starch capsule, sulbenicillin sodium is filled into capsule, sealing is carried out to capsule shells suit place with joint filling material and hard shell capsules are made, and manufactured hard shell capsules are coated with colon enteric coating coating solution；Colon enteric coating coating solution is mixed by coating material, coating solvent and plasticizer；Advantages of the present invention：The segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium obtained is provided simultaneously with segmented intestine targeted, fater disintegration and eases up the triple function of slow release medicine, extends the circulation time of oral sulbenicillin sodium in vivo, improves the absorption efficiency of sulbenicillin sodium；Compared with the special knot enteric capsule shell of prior art selection, upper probability is high, and art for coating is stablized, easily operated, is suitble to large-scale industrial production；The color and luster and transparency of rubber capsule can be kept after starch hard shell capsules coating made from this law, improves patient's compliance；It is simple for process, special installation is not required to, it is easily operated, it is of low cost.
Description
Technical field
The present invention relates to segmented intestine targeted starch capsules of a kind of highly dissoluble sulbenicillin sodium and preparation method thereof, belong to medicine
Technical field.
Background technology
Sulbenicillin sodium belongs to wide spectrum semi-synthetic penicillins antibiotic, to pseudomonas aeruginosa, proteus, large intestine bar
Following infection caused by the sensitive bacterias such as bacterium：（1）Infection in respiratory system, such as acute/chronic bronchitis, bronchiectasis, broncho-pulmonary
Inflammation, pneumonia etc.；（2）Abdominal cavity infection, such as peritonitis, cholecystitis, cholangitis；（3）Urinary system infection contamination, such as pyelonephritis, wing
Guang inflammation, urethritis etc.；（4）Gynecological infections, such as adnexitis, pelvic infecton；（5）Shallow purulent disease, such as hair follicle
Inflammation, cellulitis, tonsillitis, Complication included infection, the sexy dye of traumatic or burn etc.；（6）Septicemia；（7）It is subacute
Bacterial endocarditis.；8）Tympanitis, parotitis, paranasal sinusitis etc. have clinical application effect.
Oral colon specific targeting drug-delivery system is the novel medicine feeding mode that the nineties, Later development got up, so-called oral colon target
Refer to drug delivery system through drug delivery techniques, do not discharged in upper digestive tract after making drug oral, but drug is moved to
Start to be disintegrated after human body ileocecus or lose and solve and release, make so as to which drug be made to play locally or systemically treatment in human body large intestine
With.It is administered by oral colon-target, additionally aids the exploitation to certain sustained-release preparations for having slow-absorbing in colon and profit
With and be conducive to mitigate patient pain, improve its compliance etc..
Capsule is very extensive in the application of pharmaceuticals industry, and as shell --- the capsule shells of protection drug, it is not only
It can protect a drug from destroying, incur pollution, also reduce stimulation of the drug to respiratory tract and digestive organs.Traditional capsule
Shell is mostly made by the skin of animal, ossein, limited source, and there is a variety of security risks；Starch is that one kind derives from a wealth of sources
Renewable plant resources, property is stable, disposable acquisition, and capsule is made using it, both there is no immunogenicity, also not
The problem of having heavy metals exceeding standard, while there is the advantages that of low cost, long shelf-life, wide adaptability.
Therefore starch capsule with oral targeting drug delivery system is combined, develops capsule colon targeting preparation, undoubtedly have
There is important clinical meaning.Capsule colon targeting preparation is mostly filled in the industrial production using special colonic-coated hollow capsule shell at present
Powder charge object.It finds in actual production, probability is low on commercially available colonic-coated hollow capsule shell, and pollution instrument, brings after drug is filling
Troublesome follow-up work not only causes drug greatly to waste, more lengthens the production cycle, increase production cost, limit
Large-scale industrial production and the clinical practice of this preparation are made.
At present in segmented intestine targeted technical aspect, have related technology reports, carrier material can mainly have according to the mode of action
Three kinds, pH dependent forms, time-dependent and Bacterialtriggered.Have using in the molten casing film preparation knot of conventional capsule outer wrapping colon
Intestines targeting preparation, if CN200610043916 discloses a kind of colon target-positioning preparation and preparation method for treating colitis,
Montmorillonite medicine and pharmaceutic adjuvant are pelletized, are packed into conventional capsule, the molten casing film of outsourcing colon positions to prepare smectite middle gut
Capsulae enterosolubilis.Also there is inclusion enteric casing after drug is made pellet or particle that coating micro-pill or particle is made, be then reloaded into
Colon targeting preparation is prepared in capsule.As CN200710029476 discloses a kind of colon targeting drug administration of myocardium protein polypeptide
Preparation and preparation method thereof, it is micro- to drug containing made of the medicinal powder containing myocardium protein polypeptide ingredient using segmented intestine targeted coatings liquid
Ball is wrapped up or the medicated pellet is directly loadable into segmented intestine targeted capsule shells and is made.Also have and degraded using colon bacterium
Material, if CN200710070812 discloses colonic microflora degradation material and its preparation method and application, by cellulose sodium sulfate
(NaCS) and the compound polyelectrolyte of chitosan composition prepares colon targeting preparation as carrier.But these methods or more
Or few existing defects, pH value section bar material is as pH is in alkaline bleach liquor degradation, after intestinal environment is entered, from small intestine front end to colon pH value
It gradually rises, and basic matterial also not just starts to dissolve in the pH conditions of colon, only before colon is not reached, most of pH
It is undissolved to be worth section bar material, small part dissolving occurs, but the rupture of part film layer is likely to result in a large amount of burst releases of drug.And it uses
Colon bacterium degradation-type material, it is also possible to which, due to the difference of individual, flora difference leads to the unstability of release.
Invention content
For overcome the deficiencies in the prior art and for sulbenicillin sodium currently on the market dosage form with injectable dosage forms
Based on situation, the high-end auxiliary material kind starch capsule of world's originality that the present invention is successfully researched and developed using company, creativeness carries
Segmented intestine targeted starch capsule of a kind of highly dissoluble sulbenicillin sodium and preparation method thereof is supplied.
In order to achieve the above object, the present invention adopts the following technical scheme that：
A kind of segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium, sulbenicillin sodium is filled in starch hard shell capsules, described
Starch hard capsule case outer layer be colon enteric coat layer, the colon enteric coat layer be selected from pH degradation-type colon enteric materials or
The one or two of person's colon bacterium degradable material.
Starch in the starch capsule is tapioca, sweet potato starch, cornstarch, barley starch or its modified starch
In one or more, the preferred hydroxypropul starch of modified starch, esterification starch, and further preferred Hydroxypropyl Tapioca Starch.
The colon enteric coating coatings are mixed by pH degradation-type colons enteric material, coating solvent and plasticizer；
PH degradation-type colons enteric material is cellulose acetate benzenetricarboxylic acid ester (CAT), polyvinyl alcohol phthalate ester (PVAP), hypromellose
The mixture of one or more of plain phthalate ester (HPMCP), Eudragit E uS100 and EuL100；Coating solvent is
The mixture of one or more of ethyl alcohol, acetone and isopropanol；Plasticizer is phthalic acid ester, glyceride, amber
The mixture of one or more of acid esters, benzoic ether and citrate.
The colon enteric coating coatings can also be made of colon bacterium degradable material dispersion liquid；The colon bacterium degradation material
Expect for octenyl succinate starch.
The colon enteric coating coatings can also be by pH degradation-type colons enteric material, colon bacterium degradable material and coating
Solvent is mixed；It is preferred that cellulose acetate benzenetricarboxylic acid ester, octenyl succinate starch and ethyl alcohol are made.
Wherein starch hard capsule case suit place is sealed with joint filling material, and the joint filling material is molten by HPMC, PVA and ethyl alcohol
Liquid is made, and preferably joint filling material is made of PVA the and 80-90% ethanol solutions of HPMC, 5-15% of 1-6%.
The preparation method of the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium of the present invention, includes the following steps：System
Standby sulbenicillin sodium particle, prepares colon enteric coating liquid, sulbenicillin sodium is filled into starch hard shell capsules, ebonite is encapsulated
Mouthful, hard shell capsules are coated with colon enteric coating liquid, are drying to obtain.
Preferably include following steps：
（1）Sulbenicillin sodium crude product is added in into 95% ethyl alcohol, add in 0.5%（w/v）Ratio activated carbon, 50 DEG C of stirring and dissolvings
30 min filter out activated carbon while hot, and filtrate is cooled to 0 ~ 5 DEG C, and crystallization 5 hours filters, dry, obtains refined sulbenicillin
Sodium；
（2）The sulbenicillin sodium being refining to obtain is ultrasonic under Ultrasonic Conditions, place under microwave condition with 100 ~ 200 DEG C
30 ~ 60 min of microwave treatment, you can obtain uniform, stable, highly dissoluble sulbenicillin sodium；
（3）Prepare coating solution：50 ~ 80 parts by weight of coating solution raw material coating material add in 95% ethyl alcohol and coating solution are made；
（4）It is intracapsular that sulbenicillin sodium is filled into amylan, sealing is carried out to starch capsule shells suit place with joint filling material and being made
Hard shell capsules are coated with coating solution：The flow velocity of coating material is controlled as 30 ~ 60 ls/h, inlet air temperature is 40 ~ 70 DEG C, 28 ~ 35
The drying of DEG C relative humidity 30% ~ 50% to get.
Advantages of the present invention：The present invention is coated starch capsule by coating material in the mesh for reaching Colon-specific release
's；The color and luster and transparency of rubber capsule can be kept after capsule coating made from this law；This method is simple for process, is not required to special set
It is standby, easily operated, of low cost, suitable and industrialized production.
Specific embodiment
Embodiment 1：
The preparation of sulbenicillin sodium
Sulbenicillin sodium crude product is added in into 95% ethyl alcohol, add in 0.5%（w/v）Ratio activated carbon, 50 DEG C of stirring and dissolvings 30
Min filters out activated carbon while hot, and filtrate is cooled to 0 DEG C, and crystallization 5 hours filters, dry, obtains refined sulbenicillin sodium；It will
The sulbenicillin sodium being refining to obtain is ultrasonic under Ultrasonic Conditions, place under microwave condition with 150 DEG C of 40 min of microwave treatment,
It can obtain uniform, stable, highly dissoluble sulbenicillin sodium.
Embodiment 2：
Hard shell capsules are prepared according to common process：Sulbenicillin sodium after will be refined is filling in tapioca capsule shells, and using envelope
Gate material（HPMC5%, PVA11%, ethyl alcohol 34%, water 60% mixed solution）Capsule shells suit place is sealed, is made
Hard shell capsules；Colon enteric coating coating solution is prepared, formula is made of hypromellose phthalate, 95% ethyl alcohol, succinate,
The weight percent of each component is：Hypromellose phthalate 7.0%, 95% ethyl alcohol 90.0%, succinate 3.0%；With
Above-mentioned colon enteric coating coating solution is coated starch capsule up to colon enteric starch capsule of the present invention.
Dissolution in vitro experiment is carried out to the capsule, result is：37 DEG C, in the simulated intestinal fluid of pH=6.8 3 h dissolutions be less than
1%；37 DEG C, 1 h dissolutions 10% in the simulated intestinal fluid of pH=7.4；37 DEG C, more than 90% 1 h dissolutions in the simulated intestinal fluid of pH=7.8.It will
Barium sulfate is packed into conventional capsule, is coated with above-mentioned colon enteric coating coating solution, barium sulfate tracer capsule is made, has carried out five person-times
Internal tracking test and X-ray is checked, film making record the result shows that：After taking the capsule, wherein a people takes three barium sulfate
Tracer capsule is all disintegrated in ileocecus, and a people takes three barium sulfate tracer capsules and is all disintegrated in the colon ascendens,
The disintegration position of three that excess-three people is taken is terminal ileum position, does not appear in the situation of transverse colon disintegration.
Embodiment 3
Hard shell capsules are prepared according to common process：Sulbenicillin sodium after will be refined is filling in tapioca capsule shells, and using envelope
Gate material (HPMC5%, PVA11%, ethyl alcohol 34%, water 60%) seals capsule shells suit place, is prepared into starch ebonite
Capsule；Colon enteric coating coating solution is prepared, formula is formed sediment by cellulose acetate benzenetricarboxylic acid ester, 95% ethyl alcohol, octenyl succinate
Powder forms, and the weight percent of each component is：Cellulose acetate benzenetricarboxylic acid ester 7.0%, 95% ethyl alcohol 90.0%, octenyl succinic
Acid esters starch 3.0%；Capsule is coated up to colon enteric starch capsule of the present invention with above-mentioned colon enteric coating coating solution.
Dissolution in vitro experiment is carried out to the capsule, result is：2 h dissolutions are less than 1% in 37 DEG C of simulated gastric fluids；37
DEG C, 3 h dissolutions are less than 1% in the simulated intestinal fluid of pH=6.8；37 DEG C, 1 h dissolutions about 4% in the simulated intestinal fluid of pH=7.4；37 DEG C, pH=
1 h dissolutions 92% in 7.8 simulated intestinal fluids.Barium sulfate is packed into conventional capsule, is coated, is made with above-mentioned colon enteric coating coating solution
Barium sulfate tracer capsule has carried out five person-times of internal tracking tests and X-ray and has checked, film making record the result shows that：Take the glue
After capsule, wherein the disintegration position that three people take three barium sulfate tracer capsules is terminal ileum, two people take three as ileocecus,
The situation of the colon ascendens and transverse colon disintegration is not appeared in.
Embodiment 4
Hard shell capsules are prepared according to common process：Sulbenicillin sodium after will be refined is filling in common gelatine capsule shell, is prepared into shallow lake
Powder hard shell capsules；Colon enteric coating coating solution is prepared, is formulated by cellulose acetate benzenetricarboxylic acid ester, 95% ethyl alcohol, citrate group
Into the weight percent of each component is：Cellulose acetate benzenetricarboxylic acid ester 9.0%, 95% ethyl alcohol 90.0%, citrate 1.0%；
Capsule is coated up to colon enteric starch capsule of the present invention with above-mentioned colon enteric coating coating solution.
Dissolution in vitro experiment is carried out to the capsule, result is：2 h dissolutions are less than 1% in 37 DEG C of simulated gastric fluids；37
DEG C, 3 h dissolutions are less than 1% in the simulated intestinal fluid of pH=6.8；37 DEG C, 1 h dissolutions about 20% in the simulated intestinal fluid of pH=7.4；37 DEG C, pH
1 h dissolutions about 82% in=7.8 simulated intestinal fluids.
Embodiment 5：
Hard shell capsules are prepared according to common process：Sulbenicillin sodium after will be refined is filling in cassava hydroxypropyl starch capsule shells, and
Using joint filling material（HPMC5%, PVA11%, ethyl alcohol 34%, water 60% mixed solution）Capsule shells suit place is sealed
Mouthful, hard shell capsules are made；Colon enteric coating coating solution is prepared, is formulated by cellulose acetate benzenetricarboxylic acid ester, 95% ethyl alcohol, succinic acid
Ester forms, and the weight percent of each component is：Cellulose acetate benzenetricarboxylic acid ester 8.0%, 95% ethyl alcohol 90.0%, succinate
2.0%；Starch capsule is coated with above-mentioned colon enteric coating coating solution up to colon enteric starch capsule of the present invention.
Embodiment 6：
Hard shell capsules are prepared according to common process：Sulbenicillin sodium after will be refined is filling in tapioca capsule shells, and using envelope
Gate material（HPMC5%, PVA11%, ethyl alcohol 34%, water 60% mixed solution）Capsule shells suit place is sealed, is made
Hard shell capsules；Colon enteric coating coating solution is prepared, formula is made of polyvinyl alcohol phthalate ester, 95% ethyl alcohol, succinate, each group
Point weight percent be：Polyvinyl alcohol phthalate ester 7.0%, 95% ethyl alcohol 90.0%, succinate 3.0%；With above-mentioned colon
Enteric coating coating solution is coated starch capsule up to colon enteric starch capsule of the present invention.
Embodiment 7：
Hard shell capsules are prepared according to common process：Sulbenicillin sodium after will be refined is filling in cassava hydroxypropyl starch capsule shells, and adopts
Use joint filling material（HPMC5%, PVA11%, ethyl alcohol 34%, water 60% mixed solution）Capsule shells suit place is sealed,
Hard shell capsules are made；Colon enteric coating coating solution is prepared, formula is made of octenyl succinate starch, 95% ethyl alcohol, each group
Point weight percent be：Octenyl succinate starch 6.0%, 95% ethyl alcohol 94.0%；It is coated with above-mentioned colon enteric coating
Liquid is coated starch capsule up to colon enteric starch capsule of the present invention.
37 DEG C, 3 h dissolutions are less than 1% in the simulated intestinal fluid of pH=6.8；37 DEG C, 1 h dissolutions are about in the simulated intestinal fluid of pH=7.4
9%；37 DEG C, 1 h dissolutions 91% in the simulated intestinal fluid of pH=7.8.
One embodiment of the present of invention is described in detail above, but the content is only the preferable of the present invention
Embodiment, it is impossible to be construed as limiting the practical range of the present invention.All equivalent changes done according to the present patent application range with
Improve etc., it should all still belong within the patent covering scope of the present invention.
Claims (10)
1. a kind of segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium, which is characterized in that sulbenicillin sodium is filled in starch
In hard shell capsules, the starch hard capsule case outer layer is colon enteric coat layer, and the colon enteric coat layer is selected from pH degradation-types
The one or two of colon enteric material or colon bacterium degradable material.
2. the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium described in claim 1, which is characterized in that the amylan
Starch in capsule is one or more in tapioca, sweet potato starch, cornstarch, barley starch or its modified starch, is changed
The preferred hydroxypropul starch of property starch, esterification starch, and further preferred Hydroxypropyl Tapioca Starch.
3. the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium described in claim 1, which is characterized in that the colon intestines
Molten clothing coatings are mixed by pH degradation-type colons enteric material, coating solvent and plasticizer；PH degradation-type colon enteric materials
Expect for cellulose acetate benzenetricarboxylic acid ester (CAT), polyvinyl alcohol phthalate ester (PVAP), hypromellose phthalate (HPMCP), third
The mixture of one or more of olefin(e) acid resin EuS100 and EuL100；Coating solvent is ethyl alcohol, acetone and isopropanol
One or more of mixture；Plasticizer is phthalic acid ester, glyceride, succinate, benzoic ether and lemon
The mixture of one or more of lemon acid esters.
4. the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium described in claim 1, which is characterized in that the colon intestines
Molten clothing coatings are made of colon bacterium degradable material dispersion liquid；The colon bacterium degradable material is octenyl succinate starch.
5. the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium described in claim 1, which is characterized in that the colon intestines
Molten clothing coatings are mixed by pH degradation-type colons enteric material, colon bacterium degradable material and coating solvent；It is preferred that acetic acid is fine
The plain benzenetricarboxylic acid ester of dimension, octenyl succinate starch and ethyl alcohol are made.
6. the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium described in claim 1, which is characterized in that starch hard shell capsules
It is sealed with joint filling material shell suit place.
7. the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium described in claim 4, which is characterized in that the sealing material
Material is made of HPMC, PVA and ethanol solution.
8. the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium described in claim 4, which is characterized in that the sealing material
Material is made of PVA the and 80-90% ethanol solutions of HPMC, 5-15% of 1-6%.
9. the preparation method of the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium according to claim 1, including such as
Lower step：Sulbenicillin sodium particle is prepared, prepares colon enteric coating liquid, sulbenicillin sodium is filled into starch hard shell capsules,
Rigid capsule sealing, hard shell capsules are coated with colon enteric coating liquid, are drying to obtain.
10. the preparation method of the segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium according to claim 9, including such as
Lower step：
（1）Sulbenicillin sodium crude product is added in into 95% ethyl alcohol, add in 0.5%（w/v）Ratio activated carbon, 50 DEG C of stirring and dissolvings
30 min filter out activated carbon while hot, and filtrate is cooled to 0 ~ 5 DEG C, and crystallization 5 hours filters, dry, obtains refined sulbenicillin
Sodium；
（2）The sulbenicillin sodium being refining to obtain is ultrasonic under Ultrasonic Conditions, place under microwave condition with 100 ~ 200 DEG C
30 ~ 60 min of microwave treatment, you can obtain uniform, stable, highly dissoluble sulbenicillin sodium；
（3）Prepare coating solution：50 ~ 80 parts by weight of coating solution raw material coating material add in 95% ethyl alcohol and coating solution are made；
（4）It is intracapsular that sulbenicillin sodium is filled into amylan, sealing is carried out to starch capsule shells suit place with joint filling material and being made
Hard shell capsules are coated with coating solution：The flow velocity of coating material is controlled as 30 ~ 60 ls/h, inlet air temperature is 40 ~ 70 DEG C, 28 ~ 35
The drying of DEG C relative humidity 30% ~ 50% to get.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611173969.4A CN108201531A (en) | 2016-12-19 | 2016-12-19 | Segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611173969.4A CN108201531A (en) | 2016-12-19 | 2016-12-19 | Segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108201531A true CN108201531A (en) | 2018-06-26 |
Family
ID=62602702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611173969.4A Pending CN108201531A (en) | 2016-12-19 | 2016-12-19 | Segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108201531A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112641121A (en) * | 2020-10-10 | 2021-04-13 | 广州启键生物科技有限公司 | Preparation method of filling hollow capsules of hydroxypropyl methylcellulose and algal polysaccharide |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5764610A (en) * | 1980-10-08 | 1982-04-19 | Fujisawa Pharmaceut Co Ltd | Pharmaceutical for rectal administration |
| WO1998001159A2 (en) * | 1996-07-06 | 1998-01-15 | Danbiosyst Uk Limited | Composition for enhanced uptake of polar drugs from mucosal surfaces |
| EP0810857B1 (en) * | 1994-06-21 | 2001-08-29 | West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited | Colonic drug delivery composition |
| CN1582903A (en) * | 2004-06-11 | 2005-02-23 | 沈阳药科大学 | Plug capsules for enzyme decomposable dependent medicinal release positioned in colon and their preparation |
| CN1682699A (en) * | 2005-02-28 | 2005-10-19 | 潮州市强基制药厂 | Colon soluble and intestine soluble hollow hard capsule and producing process |
| CN1887310A (en) * | 2005-06-30 | 2007-01-03 | 天津药物研究院 | Compound fennel capsule for treating indigestion and its prepn process |
| CN101209247A (en) * | 2006-12-27 | 2008-07-02 | 天津中新药业集团股份有限公司 | Preparation of colon-targeted preparation |
| CN101653609A (en) * | 2009-08-28 | 2010-02-24 | 华南理工大学 | Octenyl succinate starch with colon targeting controlled release function and preparation method thereof |
| CN103191062A (en) * | 2013-04-15 | 2013-07-10 | 辽宁科泰生物基因制药股份有限公司 | Sulbenicillin sodium injection |
| CN104961125A (en) * | 2015-06-24 | 2015-10-07 | 上海大学 | Graphene high in solubility and preparation method thereof |
| CN105030723A (en) * | 2015-07-13 | 2015-11-11 | 湖南尔康制药股份有限公司 | Starch capsule and method for preparing same |
| CN106074439A (en) * | 2016-07-30 | 2016-11-09 | 东莞东美食品有限公司 | A kind of oxidation hydroxypropyl starch capsule and preparation method thereof |
-
2016
- 2016-12-19 CN CN201611173969.4A patent/CN108201531A/en active Pending
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5764610A (en) * | 1980-10-08 | 1982-04-19 | Fujisawa Pharmaceut Co Ltd | Pharmaceutical for rectal administration |
| EP0810857B1 (en) * | 1994-06-21 | 2001-08-29 | West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited | Colonic drug delivery composition |
| WO1998001159A2 (en) * | 1996-07-06 | 1998-01-15 | Danbiosyst Uk Limited | Composition for enhanced uptake of polar drugs from mucosal surfaces |
| CN1582903A (en) * | 2004-06-11 | 2005-02-23 | 沈阳药科大学 | Plug capsules for enzyme decomposable dependent medicinal release positioned in colon and their preparation |
| CN1682699A (en) * | 2005-02-28 | 2005-10-19 | 潮州市强基制药厂 | Colon soluble and intestine soluble hollow hard capsule and producing process |
| CN1887310A (en) * | 2005-06-30 | 2007-01-03 | 天津药物研究院 | Compound fennel capsule for treating indigestion and its prepn process |
| CN101209247A (en) * | 2006-12-27 | 2008-07-02 | 天津中新药业集团股份有限公司 | Preparation of colon-targeted preparation |
| CN101653609A (en) * | 2009-08-28 | 2010-02-24 | 华南理工大学 | Octenyl succinate starch with colon targeting controlled release function and preparation method thereof |
| CN103191062A (en) * | 2013-04-15 | 2013-07-10 | 辽宁科泰生物基因制药股份有限公司 | Sulbenicillin sodium injection |
| CN104961125A (en) * | 2015-06-24 | 2015-10-07 | 上海大学 | Graphene high in solubility and preparation method thereof |
| CN105030723A (en) * | 2015-07-13 | 2015-11-11 | 湖南尔康制药股份有限公司 | Starch capsule and method for preparing same |
| CN106074439A (en) * | 2016-07-30 | 2016-11-09 | 东莞东美食品有限公司 | A kind of oxidation hydroxypropyl starch capsule and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 叶立 主编: "《最新全科医生用药手册（第二版）》", 31 January 2006, 天津科学技术出版社 * |
| 庄越 等主编: "《实用药物制剂技术》", 31 January 1999, 人民卫生出版社 * |
| 潘贤仪 主编: "《临床实用抗菌药物治疗学》", 31 August 2011, 合肥工业大学出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112641121A (en) * | 2020-10-10 | 2021-04-13 | 广州启键生物科技有限公司 | Preparation method of filling hollow capsules of hydroxypropyl methylcellulose and algal polysaccharide |
| CN112641121B (en) * | 2020-10-10 | 2022-04-19 | 广州玖洲胶囊生物科技有限公司 | Preparation method of filled hollow capsules of hydroxypropyl methylcellulose and carrageenan |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR0155563B1 (en) | Large intestinal dissociative hard capsules | |
| JP5068401B2 (en) | Intestinal and colonic delivery using HPMC capsules | |
| EP2659881B1 (en) | A delayed release drug formulation | |
| TW299235B (en) | ||
| CN105412046B (en) | A kind of curcumin colon specific drug preparation and preparation method thereof | |
| JP2010202550A (en) | Enteric capsule | |
| US11160762B2 (en) | Modified release coated capsules | |
| CN101108171A (en) | Budesonide intestines sustained release dextromethorphan pellets and method of manufacturing the same | |
| CN108042503B (en) | High-efficiency potassium sodium dehydroandroan drographolide succinate enteric-coated tablet and preparation method thereof | |
| CN103127026B (en) | Omeprazole enteric capsule and prepared method thereof | |
| US6752953B2 (en) | Method for manufacturing hard non-gelatin pharmaceutical capsules | |
| CN108201531A (en) | Segmented intestine targeted starch capsule of highly dissoluble sulbenicillin sodium and preparation method thereof | |
| CN103908441A (en) | Enteric-coated soft capsule of Omega-3 aliphatic acid and its derivative and preparation method of the enteric-coated soft capsule | |
| CN107982241A (en) | A kind of andrographolide enteric coated preparations and preparation method | |
| CN105434398B (en) | A kind of Rabeprazole enteric-coated micro-pill and preparation method thereof | |
| CN104784154A (en) | Site-specific osmotic-pump controlled-release capsule shell and preparation method thereof | |
| CN101209247B (en) | Preparation of colon-targeted preparation | |
| CN101596162B (en) | Doxycycline hyclate enteric-coated pellet | |
| CN105617391B (en) | A kind of scutelloside colon specific drug preparation and preparation method thereof | |
| CN102552163B (en) | Metoprolol tartrate sustained release pellet and preparation method thereof | |
| EP3662902B1 (en) | Colonic drug delivery formulation | |
| TWI530299B (en) | Pharmaceutical composition for preparing drug delivery nano/micro bubbles | |
| CN101732280B (en) | Oral preparation of novel colonic positioning release medicine | |
| MX2009001085A (en) | Coating composition comprising starch. | |
| TWI718100B (en) | Positive pressure capsule and manufacturing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180626 |