CN101495104A - Coating composition comprising starch - Google Patents

Abstract

The present invention provides a coating composition comprising an aqueous medium and, dispersed therein, starch and a film-forming agent which controls swelling of the starch by the aqueous medium. Formulations comprising the coating composition are also provided. The formulations may be useful in the treatment or diagnosis of colonic disease.

Description

The coated composition that contains starch

Technical field

The present invention relates to coated composition and uses thereof, for example be used for the purposes of the preparation of colonic drug delivery in preparation.

Background of invention

The medicine and the rectum that mainly absorb in the harmonization of the stomach small intestinal by orally give give seldom successfully to arrive all very difficult treatment of colon ascendens medicine such as colonic diseases and morbid states such as inflammatory bowel, colorectal carcinoma, constipation and infection.Colonic drug delivery has been used to overcome these restrictions.Any system with drug specificity targeting colon all has significant advantage, reduces the remarkable side effect of required oral dose and reduction such as medicines such as corticosteroid.

The oral administration that enters body circulation vaccine, albumen and therapeutical peptide also is subject to remarkable degraded in the sour environment of stomach and the enzymatic degradation in the small intestinal.On the contrary, colon has lower enzymatic activity and near neutral pH, therefore enters body circulation inlet as these materials.

Can service time dependency system, pH dependency system or based on the system of the enzymatic activity of colon to realize with reactive compound targeting colon.As if the system based on the enzymatic activity of colon provides high specific in the site of drug release, and this is because this system depends on by the specificity degraded of colon microbiota to biodegradable polymer.These biodegradable polymer mainly are polysaccharide, can be the parts of coating or only are that substrate forms material.This coating system provides higher medicament contg expediently.

Coated composition based on the amylose of glassy form and crystal form is known.The amylose of glassy form is considered to the degraded of anti-pancreatic, but still the fermentation of process colonic enzyme.Said composition comprises the aqueous dispersion of amylose usually.Because amylose is by aqueous medium institute swelling, so said composition also comprises the swollen material of control amylose.Usually, this material is a water-insoluble polymer, as ethyl cellulose.

Milojevic etc. (J.Control.Release, 38,75-84,1995) have described the complicated approach that extracts amylose from the starch of smooth bark kind type Semen Pisi sativi, finally obtain amylose-Ding-1-alcohol coordination compound.The aqueous dispersion of this amylose coordination compound at high temperature (is generally 70 ℃) with different w/w than mixing with Aquacoat then.Such high temperature is the described coordination compound of fusion and to obtain amylose solution necessary.Formation glassy or crystalloid amylose film depends on the rate of drying in the film coating procedure.

US 6534549 described by with the aqueous dispersion of amylose-Ding-1-alcohol coordination compound be dissolved in the miscible organic solvent of water in the solution of ethyl cellulose mix the amylose coated composition that forms mutually, the miscible organic solvent of described and water is ethyl lactate for example.In these dispersions, the ratio of amylose and ethyl cellulose is that 1: 2 to 3: 2 and dicyandiamide solution comprise the organic solvent of 50%w/w at least.Usually, the temperature that is used for this method need not to be higher than 60 ℃ and often can be ambient temperature.

US 2005/0220861 has described and has used the compositions that contains glassy amylose, ethyl cellulose and dibutyl sebacate to come coating to contain the piller of iodo-benzoic acid sodium between meticortelone.Said composition is obtained by following method: heat and use the aqueous solution or the water/alcoholic solution of the mutually blended glassy amylose of the plastifying Aquacoat of dibutyl sebacate, thereby obtain the amylose of amorphous form.

Though amylose has been used for multiple coated composition, it must be to use with glassy or unbodied form, and this needs tediously long and complicated operations.Still needing badly provides specificity to discharge in colon and can be simply and the coated composition for preparing easily.

Summary of the invention

The present invention to small part based on such discovery, the coated composition that contains starch is specially adapted to the colon of therapeutic agent and diagnostic agent and carries.Starch is degraded specifically by the colon microbiota, and this makes it become the ideal selection of drug conveying to the colon.In addition, be different from amylose, starch need not to be processed into glassy form or amorphous form.Discharge before arriving colon for fear of activating agent, compositions of the present invention also comprises help and forms film and control the swollen reagent of starch.

Therefore, a first aspect of the present invention provides and contains aqueous medium and disperse starch wherein and control this starch by the coated composition of the swollen film former of this aqueous medium.

A second aspect of the present invention provides the preparation with the described compositions coating of arbitrary aforementioned claim.

Be the method for treatment or diagnosis colonic diseases or morbid state on the other hand, comprise giving preparation of the present invention.

The present invention also provides the method for preparing the present composition, and it comprises aqueous medium, starch and control starch are mixed mutually by the swollen film former of aqueous medium.

The present invention also provides the method for the treatment local disease relevant with colon, and it comprises and gives preparation of the present invention.As an example, local disease comprises Crohn disease, ulcerative colitis, colorectal carcinoma and amebiasis.

Coated composition of the present invention provides specificity in the site of drug release.Adopt the various active composition, preparation of the present invention can be used for the topical therapeutic of colonic diseases and morbid state or is used to carry being intended to the albumen and peptide and the vaccine that are absorbed by mucous membrane of colon.Therefore, the present invention can find purposes in the treatment of inflammatory bowel, colorectal carcinoma, constipation and infection.Can change coating thickness with targeting, for example in the drug release or the absorption of distal small intestine or proximal colon, transverse colon or DC.Preparation of the present invention can allow the sustained release of one or more active component.

Brief description of drawings

Fig. 1 shows by the piller of coating not and plastifying with the 10%w/w dibutyl sebacate

(the increasing to 8%, 16% and 24% of gross weight) piller drug release under pH 1.2 of coating.

Fig. 2 shows with containing The drug release of piller under pH 7.2 of the compositions coating of (the increasing to 8%, 16% and 24% of gross weight) and 10%w/w dibutyl sebacate.

Fig. 3 shows with the ratio that contains 1: 4 and 1: 5

Compositions, carry out the drug release of piller under pH 1.2 of coating with different coat weight increases.

Fig. 4 shows with the ratio that contains 1: 4 and 1: 5

With Compositions, carry out the drug release of piller under pH 7.2 of coating with different coat weight increases.

Fig. 5 shows with the ratio that contains 1: 5

With

The drug release of (the increasing to 24% of gross weight) piller under pH 1.2 and pH 7.2 of compositions coating.

Fig. 6 shows usefulness

The drug release of (the increasing to 25% of gross weight) piller under pH 1.2 and pH 7.2 of coating.

Fig. 7 shows with the ratio of 1: 2 and 1: 5

With The drug release of piller in mimic gastric juice of coating (increase of gross weight is respectively 30% and 24%).

Fig. 8 shows with the ratio of 1: 2 and 1: 5

With

The drug release of piller in mimic gastric juice of coating (increase of gross weight is respectively 30% and 24%).

Fig. 9 shows with the ratio of 1: 2 and 1: 5

With

The drug release of piller in mimic intestinal juice of coating (increase of gross weight is respectively 30% and 24%).

Figure 10 shows with the ratio of 1: 2 and 1: 5

With

The drug release of piller in mimic intestinal juice of coating (increase of gross weight is respectively 30% and 24%).

Figure 11 shows with the ratio of 1: 2 and 1: 5

With

The piller of coating (increase of gross weight is respectively 30% and 24%) discharges 2 hours, discharged 4 hours in mimic intestinal juice (SIF) then and 18 hours drug release of release in mimic colonic fluid (SCF) in mimic gastric juice (SGJ).

Figure 12 shows with the ratio of 1: 2 and 1: 5

Or

With

The piller of (increase of gross weight is respectively 30% and 24%) discharges 4 hours and discharge 20 hours drug release then in mimic colonic fluid (SCF) in mimic intestinal juice (SIF).

The description of multiple embodiments

Coated composition of the present invention comprises aqueous medium and disperses starch wherein and control described starch by the swollen film former of described aqueous medium.

Described aqueous medium can be any suitable medium as known in the art, and can randomly comprise non-aqueous (for example organic) medium.In specific embodiment, described medium is water or water/alcohol (for example water/ethanol) mixture.

Starch is scattered in the described aqueous medium.Term used herein " starch " comprises the carbohydrate that contains amylose and amylopectin.Can use and have different amylosies: the multiple starch of amylopectin ratio.Described starch can comprise, for example, and about 10% to about 80% amylose and about 20% to about 90% amylopectin.Preferred starch comprises about 50% to about 30% amylopectin.Also it is worth mentioning the starch of high amylose starches, promptly contain a large amount of relatively amylosies and the starch of a spot of amylopectin respectively.It is worth mentioning the starch that contains at least 40% amylose especially, at least 50% amylose more particularly, more particularly at least 60% amylose and especially at least 70% amylose.The example of suitable starch comprises

(corn starch that contains 70% amylose of having an appointment) and

(corn starch that contains 50% amylose of having an appointment), they all can derive from National Starch and ChemicalCompany.

In the presence of aqueous medium, starch experiences the swelling of significance degree usually.If starch is swelling too, active component may discharge before preparation arrives colon.Therefore, coated composition of the present invention also comprises the swollen film former of control starch.This reagent normally suppresses the swollen reagent of starch, but can have such situation: use to promote that the swollen reagent of starch is desired.Suitable reagent comprises water-fast basically material.It is worth mentioning water-insoluble polymer basically especially, concrete example be ethyl cellulose and hypotonicity polymethacrylates (for example

RS or similar).Reagent such as ethyl cellulose can be with the form of dispersion, and especially the form of aqueous dispersion is used.

Described compositions also can comprise plasticizer with the porosity of the formation that promotes coating, control coating with improve the mechanical performance of coating.Many different plasticizers are known, and the example comprises such as the dicarboxylic ester of triethyl citrate, glycerol triacetate, acetyl tributyl citrate, tributyl citrate, glyceryl triacetate and dibutyl sebacate and tricarboxylic ester.

Described coated composition can make by aqueous medium, starch and film former are mixed simply.

In order to explain, coated composition of the present invention can be prepared as follows.At first starch is scattered in water or another aqueous medium, forms starch dispersions.This step can for example about 75 ℃ to about 85 ℃, be carried out under particularly about 80 ℃ temperature in about room temperature to about 100 ℃.Cool off dispersions obtained (for example being cooled to) in case of necessity at least about 60 ℃ to about 70 ℃.Then described film former is added in this starch dispersions.This step can be by adding the dispersion form, for example the film former of aqueous dispersion form and realizing.It is worth mentioning the dispersion of ethyl cellulose in water or water/alcohol mixture.In one embodiment, the aqueous dispersion that will contain described film former and plasticizer adds described starch dispersions.Can use the aqueous dispersion that contains ethyl cellulose and dibutyl sebacate herein.It is worth mentioning and contain ethyl cellulose, dibutyl sebacate and one or more stabilizing agents (for example from Colorcon's

Dispersion) aqueous dispersion.

This coated composition can be used for pharmaceutical preparation or other (for example diagnosis) preparation then.Suitable coating method in this area, for example fluid bed and coating pan method are well-known.The present invention's one special advantage is that coating need not ripening usually after application.

The thickness of coating also influences the speed that active substance discharges from dosage form.Depend on the dissolubility of active substance in dosage form, discharge slower usually when using thicker coating.When using the active substance of highly dissoluble, also need to use thicker coating can fully control the dosage form that active substance discharges in colon with preparation.

Can access suitable thickness by routine test, but as instruction, we can say the thickness of usually preferred about 10 μ m to 60 μ m, especially about 20 μ m are to about 50 μ m.Under many circumstances, the thickness of coating should be at least 30 μ m.It is worth mentioning that especially coating thickness is extremely about 60 μ m of about 30 μ m, for example about 40 μ m are to about 50 μ m.Thickness that can the optimization coating discharges at the specificity at target position place to guarantee active component.Changing coating thickness can also make the reactive compound of different solubilities can the targeting colon.

Coating thickness can also be defined as the increase of gross weight, i.e. the percentage ratio that weight of formulation increases during coating.It typically is 10% to 40%.Especially, can use the coating of increasing to of gross weight about 15% to about 40%, more preferably from about 20% to about 35% coating.

The stripping curve of active component can also be controlled by the ratio that change is present in the component in the described coated composition.Like this, medicine is released in minimize in the upper gastrointestinal and in colon, maximizes.Under multiple situation, it is desired than the starch of small scale and the film former of relatively large ratio relatively that described compositions comprises.Therefore, for example, starch can be about 1: 1 to about 1: 6 to the ratio of film former.Especially, this ratio is about 1: 2 to about 1: 5, for example about 1: 4 to about 1: 5.

Highly acid gastric juice can interact with coating, makes starch be difficult to be digested.In this case, use to suppress described preparation under one's belt the other enteric coating of stripping may be desired.Can use any suitable enteric coating as known in the art.It is worth mentioning dissolved enteric coating under pH 5.5 or higher pH.It is worth mentioning the enteric coating (for example Kollicoat MAE 30DP) of the aqueous dispersion that contains EUDRAGIT L100-55 especially.

Common preparation of the present invention is the solid form that is suitable for oral administration.Suitable form comprises pill, tablet, capsule, powder, granule and extrudate form.Pill can be spheric basically, has the diameter of about 0.1mm to about 5.0mm usually, and for example about 0.5mm is to about 5.0mm, and particularly about 0.5mm is to about 2.5mm, and more particularly, about 0.8mm is to about 1.5mm.

Described preparation can comprise one or more active component.Term used herein " active component " comprises food, medicine and other therapeutic agent, diagnostic agent and conductive component, and without limits.It is worth mentioning the treatment that is used for physianthropy or veterinary or the chemical compound or the compositions of diagnosis especially.Therapeutic agent comprises medicine, vaccine, albumen and therapeutical peptide.These reagent can be absorbed by colon easily or can be used for the topical therapeutic colonic diseases.It is worth mentioning aminosalicylate (for example balsalazide, mesalazine, Olsalazine and sulfasalazine) and cortical steroid (hydrocortisone, budesonide and prednisolone).Alternatively or additionally, described preparation can comprise one or more diagnostic agents.Diagnostic agent comprises, for example, is applicable to the reagent of X ray and NMR imaging technique.Optionally diagnostic field comprises and may be delivered to colon with diagnosis of allergies by allergenic food component.Described activating agent or each activating agent are present in the nuclear of using present composition coating usually.

Preparation of the present invention can comprise active component, this active component starch and swelling controlling agent coating, and be suitable for can resisting or control starch in upper gastrointestinal swelling in the mode that in colon, discharges by the active component that allows consumption.Usually, said preparation has the coating that stops starch to contact with liquid in last (before the colon) GI road.In one embodiment, suitably, said preparation also comprises diluent, excipient and/or carrier.

The present invention is in preparation comprises such as polypeptide, albumen and the medicine such as the nucleic acid molecules of oligonucleotide, and for example vaccine can have special application.Because limit protein and polypeptide are comprised that by the biological barrier that gastrointestinal (GI) road absorbs pH variability, enzymatic degradation and film efflux, oral delivery albumen, polypeptide and be a difficult problem such as the nucleic acid molecules of oligonucleotide.Therefore, the invention provides can the targeting colon compositions, colon has lower proteolytic activity than the other parts in GI road and therefore can be used in particular for medicine based on polypeptide, albumen or nucleic acid molecules.Therefore, in an embodiment of the present invention, described compositions comprise be selected from polypeptide, albumen, such as the nucleic acid molecules of oligonucleotide or the active component of its combination.

One concrete active component is 5-aminosalicylic acid (5-ASA), and it is used orally in the medicine of treatment colonic disorders.When giving free 5-ASA, because the harmonization of the stomach small intestinal makes this medicine inactivation and/or absorbed this medicine, so this medicine of minute quantity can arrive colon when oral.The invention provides the compositions that contains 5-ASA, it can slowly discharge a large amount of active component by oral administration and in colon.Preferably provide 5-ASA with the spherula form, this spherula is to mix with microcrystalline Cellulose and suitably round as a ball, and can add small part such as bentonitic inorganic bond, but optional.

Can change the described active component in the preparation or the actual dose level of each active component, thereby obtain to reach effectively the amount of desired therapeutic response to specific patient, compositions and administering mode.Selected dosage level will depend on the seriousness of the activity, route of administration of specific compound, the morbid state of being treated and the patient's that treated situation and previous medical history.Yet, be in the art technology scope until reaching desired effect from being lower than for realizing that the required chemical compound dosage level of desired curative effect begins and increases dosage gradually.

The exemplary dosage level of active component is about 0.01 to about 500mg per kilogram weight in patients every day, and it can be with single dose or multiple dose administration.Especially, dosage level can be about 0.1 to about 250mg/kg every day, 0.5 to about 100mg/kg every day according to appointment.Suitable dosage level can be about 0.01 to 250mg/kg every day, about 0.05 to 100mg/kg every day, perhaps about 0.1 to 50mg/kg every day.In this scope, dosage can be 0.05 to 0.5,0.5 to 5 or 5 to 50mg/kg every days.For oral administration, preparation can contain 1.0 to 1000 milligrams of active component, particularly 1.0,5.0,10.0,15.0,20.0,25.0,50.0,75.0,100.0,150.0,200.0,250.0,300.0,400.0,500.0,600.0,750.0,800.0,900.0 and 1000.0 milligrams of active component are regulated the dosage that gives patient to be treated according to symptom.Preparation can be with 1 to 4 time scheme administration every day, preferably once a day or twice.Can adjust dosage so that best therapeutic response to be provided.

Should be appreciated that described active component or each active component can mix mutually with the carrier mass that is suitable for its special purposes.Therefore, described preparation, especially its nuclear also can comprise one or more: a) such as the filler or the bulking agent of starch, lactose, sucrose, glucose, mannitol and silicic acid; B) such as the binding agent of carboxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose and Radix Acaciae senegalis; C) such as the wetting agent of glycerol; D) comprise disintegrating agent such as the inorganic compound of iron oxides, barium sulfate and calcium carbonate; E) such as the dissolving blocker of wax; F) such as the absorption enhancer of quarternary ammonium salt compound; G) such as the wetting agent of hexadecanol and glyceryl monostearate; H) such as Kaolin and bentonitic absorbent; I) such as the lubricant of Talcum, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and composition thereof.Said preparation also can comprise buffer agent.

The present invention comprises that also starch is used for discharging the medicine of one or more active component or the purposes in the diagnostic preparation at colon in preparation.

In one embodiment, described medicine comprises polypeptide, albumen or such as nucleic acid molecules or its combination of oligonucleotide.Preferably, described medicine comprises the active substance that decomposes usually in last GI road before arriving colon.

In one embodiment, described medicine is the disease that is used for the treatment of for colon local disease.As an example, this local disease can be selected from Crohn disease, ulcerative colitis, colorectal carcinoma and amebiasis.

Should be appreciated that purport of the present invention includes but not limited to aforesaid medicine and diagnostic preparation with the coating that comprises starch, wherein said starch is not glassy or unbodied but part or be crystalline basically, partially crystallizable for example.

The present invention comprises that also the influence of protecting pharmaceutical preparation or diagnostic preparation to avoid the enzyme in GI road allows simultaneously by the method for colonic enzyme attack, and it comprises uses the coating material that contains starch to described preparation.

The present invention of following examples exemplary illustration.

Embodiment

Embodiment 1: the preparation of coated pellets

The preparation of medicine carrying piller

By extrude spheronization preparation contain 50% model drug 5-aminosalicylic acid (5-ASA) and microcrystalline Cellulose (

PH 101) a plurality of pillers.With 5-ASA, microcrystalline Cellulose (50: 50w/w) mix to form wet piece, then it is extruded also round as a ball to form a plurality of pillers with required distilled water.Then should a plurality of pillers at room temperature on the porous pallet dry 48 hours, sieving and obtaining size is a plurality of pillers of 1.00 to 1.40mm.

The preparation of starch coating

Will

Be scattered in the water and and heat down at 80 ± 5 ℃.Use 10%w/w dibutyl sebacate corresponding to the starch dry weight to dispersions obtained plasticising.Attempt multiple coating thickness by the amount that changes the starch in the coating dispersion.

The preparation of starch-ethyl cellulose coating

Will under the condition of continuous stirring

Starch or

Starch is scattered in the water and under 80 ± 5 ℃ temperature and heats.Make dispersions obtained cooling, under continuous stirring, add then ethyl cellulose ( ) dispersion mixes fully until described dispersion.By changing in the coating dispersion

Amount preparation have the coating of different-thickness.Prepare and contain 1 part With the plastifying ethylcellulose dispersion of 4 or 5 parts of usefulness 10% dibutyl sebacates (corresponding to the dry weight of polymer) (

) dispersion.

The preparation of ethyl cellulose coating

Under the condition identical with starch-ethylcellulose dispersion by By preparing ethylcellulose dispersion at 70 ℃ of commensurability distilled water of following mixed phase.

The coating of piller

Use the Wurster fluidized bed coating, with above-mentioned dispersion with 5-ASA piller coating.In whole coating process, dispersion is remained on 70 ℃.The coating parameter is: inventory 30g, 60 ℃ of inlet temperatures, 45 ℃-50 ℃ of product temperature, outlet temperature 40-45 ℃, flow velocity 0.7-0.8ml/min, nozzle diameter 1.00 diameters, atomization air pressure 2.2 to 2.4 crust.Under 60 ℃ with the piller of coating in fluid bed dry 10 minutes.Need not the ripening of film coating.

Embodiment 2: drug release studies

Use the dissolution instrument to measure the release of 5-ASA from the coated pellets of embodiment 1 by USP oar method.All tests all are under the 100rpm, maintain in the 900ml dissolution medium under 37 ± 1 ℃ and carry out 3 times at rotating speed of agitator.The dissolution medium that uses is: (a) 0.1N HCl (pH 1.2), (b) phosphate buffer (pH 7.2), (c) mimic gastric juice, (d) mimic intestinal juice and (e) mimic colonic fluid.Stripping curve such as Fig. 1 are to shown in Figure 12.

Piller with the starch coating

Fig. 1 and Fig. 2 show with the piller of starch and the plasticizer coating stripping curve under pH 1.2 and pH 7.2 respectively.Because starch is by aqueous solvent height swelling, under these conditions, these pills have discharged the medicine of significant quantity.

Piller with the ethyl cellulose coating

Fig. 6 shows the stripping curve with the piller of ethyl cellulose coating.This illustrated example explanation does not have the ethyl cellulose of starch not discharge any medicine.

Piller with starch and ethyl cellulose coating

Fig. 3 and Fig. 4 show with the piller of starch, ethyl cellulose and the plasticizer coating stripping curve under pH 1.2 and pH 7.2 respectively.Estimated starch: the effect of the effect of the ratio of ethyl cellulose and the increase of gross weight.Discovery is with respect to the amount of starch, and the amount that increases ethyl cellulose significantly reduces dissolution rate.The increase that increases gross weight has similar effect.Starch: the ratio of ethyl cellulose is that 24% the coating of increasing to of 1: 5 and gross weight causes medicine dissolution rate minimum under each pH that is surveyed.

Fig. 5 illustrates the effect of using the starch with not commensurability amylose.

Also containing the mimic gastric juice (SGJ of pepsin and pancreatin respectively; B.P.2005, appendix XII-B-A187) and the selected preparation of the middle evaluation of mimic intestinal juice (SIF).To shown in Figure 10, in 8 hours of test, in these liquid, only observe inappreciable drug release as Fig. 7.

Use bacillus licheniformis alpha-amylase in the phosphate buffer of pH 7.2 (concentration of α-Dian Fenmei is 50U/ml to 500U/ml) simulation colonic environment then.In this test, piller was remained in the mimic gastric juice (SGJ) 2 hours, then in mimic intestinal juice (SIJ) 4 hours and in colon simulated solution (SCF) 18 hours, perhaps in SIJ 4 hours then in SCF 20 hours, purpose was to estimate the influence of acid to coated preparation.

Figure 11 shows specific pill is transferred to SIF and then the result of (SCF) to mimic colonic fluid from SGF.When being 1: 5 with ratio

With (the increasing to 24% of gross weight) piller of coating is placed in SGF when being transferred to SIF then, and drug release has been suppressed.

As shown in figure 12, when being placed in, described preparation place SCF to observe different curves in the time of 20 hours among the SIF then.In this case, compare with Figure 11, the drug release height in SCF shows and may certain interaction take place the component and the hanging down between the pH of SGF of coating.

In a word, contain 1 part

With 5 parts

, gross weight increase to drug release in the simulated environment that 24% coating dispersion is suppressed at the harmonization of the stomach small intestinal.In the presence of colonic enzyme, the release of 5-ASA is very high, and this makes this system for being feasible with drug conveying to colon.

Claims (30)

1. coated composition, it contains aqueous medium and disperses starch wherein and control described starch by the swollen film former of described aqueous medium.

2. compositions as claimed in claim 1, wherein said aqueous medium is a water.

3. compositions as claimed in claim 1, wherein said aqueous medium comprise water and alcohol (for example ethanol).

4. the described compositions of arbitrary as described above claim, wherein said starch comprise about 10% to about 80% amylose and about 20% to about 90% amylopectin.

5. the described compositions of arbitrary as described above claim, wherein said starch comprises about 30% to about 80% amylose.

6. compositions as claimed in claim 5, wherein said starch comprise about 50% to about 70% amylose.

7. the described compositions of arbitrary as described above claim, wherein said film former suppress described starch by described aqueous medium swelling.

8. the described compositions of arbitrary as described above claim, wherein said film former is water-fast basically.

9. compositions as claimed in claim 8, wherein said film former are water-insoluble polymer basically.

10. compositions as claimed in claim 9, wherein said film former comprises ethyl cellulose.

11. the described compositions of arbitrary as described above claim, wherein said starch is about 1: 1 to about 1: 6 to the ratio of described film former.

12. the described compositions of arbitrary as described above claim, it also contains plasticizer.

13. compositions as claimed in claim 12, wherein said plasticizer are dibutyl sebacate.

14. preparation with the described compositions coating of aforementioned arbitrary claim.

15. preparation as claimed in claim 14, it contains at least a active component.

16. preparation as claimed in claim 15, it comprises the nuclear that contains at least a active component, and wherein said nuclear is with described compositions coating.

17. as claim 15 or 16 described preparations, wherein said active component is medicine, vaccine, albumen or polypeptide.

18. as the described preparation of arbitrary claim in the claim 15 to 17, wherein said active component is a diagnostic agent.

19. as the described preparation of arbitrary claim in the claim 14 to 18, it also comprises outside enteric coating.

20. preparation as claimed in claim 19, wherein said enteric coating comprises copolymer, and described copolymer obtains by making the monomer polymerization that comprises methacrylic acid and ethyl acrylate.

21. the described preparation of arbitrary claim in the claim 15 to 19, it is used for the treatment of or diagnoses.

22. preparation as claimed in claim 21, it is used for the treatment of or diagnoses colonic diseases or colonic diseases state.

23. as preparation as described in arbitrary claim in the claim 15 to 22, it is a controlled release preparation.

24. the method for treatment or diagnosis colonic diseases or colonic diseases state, it comprises and gives the described preparation of arbitrary claim in the claim 15 to 23.

25. the described method for compositions of arbitrary claim in the preparation claim 1 to 13, it comprises the described starch of aqueous medium, starch and control is mixed mutually by the swollen film former of described aqueous medium.

26. method as claimed in claim 25, it comprises the dispersion that contains starch is mixed with the dispersion that contains described film former.

27. method as claimed in claim 26, wherein each dispersion is aqueous dispersion.

28. as claim 26 or 27 described methods, the described dispersion that wherein contains described film former also comprises plasticizer.

29. as the described method of arbitrary claim in the claim 25 to 28, it also comprises with described compositions coated preparation.

30. the purposes of the described preparation of arbitrary claim in treatment or diagnosis colonic diseases or colonic diseases state in the claim 15 to 23.

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