CN101548961B - Novel oral capsule preparation for curing diabetes mellitus and obesity - Google Patents
Novel oral capsule preparation for curing diabetes mellitus and obesity Download PDFInfo
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- CN101548961B CN101548961B CN2008100108947A CN200810010894A CN101548961B CN 101548961 B CN101548961 B CN 101548961B CN 2008100108947 A CN2008100108947 A CN 2008100108947A CN 200810010894 A CN200810010894 A CN 200810010894A CN 101548961 B CN101548961 B CN 101548961B
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Abstract
The invention relates to an oral capsule preparation for curing diabetes mellitus and obesity. The invention adopts the technical scheme that the capsule preparation is of a double-layer capsule structure, and a drug layer, a water-solution capsule and an enteric capsule are arranged in the double-layer capsule structure in sequence from inside to outside. According to a measuring unit, the weight of a protein drug is 0.02-5.0 milligrams, the weight of absorption-supporting agent is 20-150 milligrams, and the weight of protease inhibitor is 300-600 milligrams; the protein drug is Pramlintide or Agral; the absorption-supporting agent is bezoar deoxycholic acid or lauroyl-carnitine; and the protease inhibitor is citric acid. The preparation method comprises the following steps: the protein drug, the absorption-supporting agent for the intestinal tract and the protease inhibitor are evenly mixed according to the blending ratio, the water-solution capsule is covered by a compound body, and then a layer of enteric capsule is applied. The invention solves the problem of low absorptivity of the oral protein drug, eases the problem that the protein type oral medicine is degraded in the intestinal tract by the protease, meanwhile, the absorptivity of the protein drug in the intestinal tract is improved, and the Pramlintide and the Agral oral drugs can reach the therapeutic concentration inside the body.
Description
Technical field: the present invention relates to drug world, relate in particular to a kind of polypeptide class Drug Capsule oral formulations with treatment diabetes and obesity of bilayer or multiple structure.
Background technology: Pramlintide (Pramlintide) and Ai Gelei peptide (Exenatide) are the peptide drugs of treatment diabetes and obesity.Developed the injection dosage form by California, USA Santiago Amylin drugmaker at present, gone on the market by drugs approved by FDA, treated a type and type-II diabetes, and the curative effect of obvious treatment obesity has been arranged simultaneously.Pramlintide (Pramlintide) is 37 amino acid polypeptides, and Ai Gelei peptide (Exenatide) is 39 amino acid polypeptides.These two amino acid sequence of polypeptide are as follows:
Pramlintide, Pramlintide:H-Lys-Cys-Asn-Thr-Ala-Thr-Cys-Ala-Thr-Gln-Ar g-Leu-Ala-Asn-Phe-Leu-Val-His-Ser-Ser-Asn-Asn-Phe-Gly-Pr o-Ile-Leu-Pro-Pro-Thr-Asn-Val-Gly-Ser-Asn-Thr-Tyr-NH
2
The Ai Gelei peptide, Exenatide:H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH
2
The injection dosage form of this two peptide species is gone on the market by drugs approved by FDA, with the same usefulness of insulin, or private, to control a type and type-II diabetes patient's blood sugar level.The main mechanism of this medicine is to slow down the gastrointestinal tract emptying time and to the absorption of nutrient substance, reduces the glucagon that food brings out simultaneously and discharges.Verified this medicine of clinical experiment has obvious control or reduces the body weight effect the obesity patient in blood sugar lowering.
This medicine needs to use throughout one's life to diabetics, and every day 2-3 time is so there is problems such as using inconvenience and expensive price in the injection dosage form.And peroral dosage form has following major obstacle technically.(1) the easy protein degradation medicine of pepsin---Pramlintide (Pramlintide) and Ai Gelei peptide.(2) intestinal protease is under alkali condition, protein degradation medicine---Pramlintide (Pramlintide) and Ai Gelei peptide.(3) intestinal absorption obstacle: hydrophilic Pramlintide (Pramlintide) and Ai Gelei peptide are difficult for greatly being absorbed owing to molecular weight.(4) the intestinal rete malpighii combines with charged molecule, hinders to absorb.
Summary of the invention:, the invention provides a kind of easy to use, the treatment diabetes that absorbance is high and the oral capsule preparation of obesity in order to address the above problem.The technical solution used in the present invention is: a kind of oral capsule preparation for the treatment of diabetes and obesity is characterized in that: described capsule preparations is double-deck capsule structure, is medicine layer, water-soluble capsule and enteric coated capsule from inside to outside successively.
Described medicine layer is divided into three kinds of forms: first kind, the medicine layer is by albumen medicine, the mixture that helps absorbent and protease inhibitor to form.Second kind, the mixture that the medicine layer is made up of some Caplets and protease inhibitor, described Caplet are to coat the albumen medicine in the capsule and helping absorbent.The third, the mixture that the medicine layer helps the mixture of absorbent to form by some Caplets and protease inhibitor and part; Wherein, Caplet is to coat the albumen medicine in the capsule and surplus helps absorbent.
The oral capsule preparation of treatment diabetes and obesity, in the unit metering (a unit metering is meant a capsules), the albumen medicine, help the proportioning of absorbent and protease inhibitor to be: the albumen medicine is the 0.02-5.0 milligram, and helping absorbent is the 20-150 milligram, protease inhibitor 300-600 milligram.
Preferably, in the unit metering, the albumen medicine, help the proportioning of absorbent and protease inhibitor to be: albumen medicine 0.1-2.0 milligram; Helping absorbent is the 50-100 milligram, and protease inhibitor is the 400-500 milligram.
Among the present invention,
Described albumen medicine is Pramlintide or Ai Gelei peptide.
The described absorbent that helps is one or both mixing of Deoxycholyltaurine or lauroyl carnitine.
Helping absorbent is the chemical substance that can improve Pramlintide and Ai Gelei peptide bioavailability.Helping absorbent can be anionic surface active substances, cationic surface active substances, non-ionic surface active agent etc., and anion, the mixture of son and non-ionic surface active agent etc. of developing.It is acid solvable that these help absorbent to have, the mixture of cation and non-ionic surface active agent etc.It is acid solvable, particularly solvable between pH 2.0 to 5.0 that these help absorbent to have.Concrete, anionic surface active substances has Salicylate, bile acids; Salicylate be sodium salicylate, 3-methyl salicylate, 5-methyl salicylate and but vanilate etc.; Bile acids such as taurocholic acid, taurodeoxycholic acid, deoxycholic acid, chenodeoxycholic acid, ursodesoxycholic acid, Fel Ursi acid, dehydrocholic acid, fusidic acid etc.Cationic surface active substances has dioctyl sodium sulfosuccinate, phospholipid, acylcarnitine class, acyl gallbladder lipid, acylamino acid and alkyl saccharide, phospholipid such as PHOSPHATIDYL ETHANOLAMINE; The acylcarnitine class, acyl gallbladder lipid and acylamino acid such as lauroyl carnitine, myristoyl carnitine, lauroyl choline etc.; Alkyl saccharide such as lauroyl maltoside, lauroyl sucrose, myristoyl sucrose etc.Non-ionic surface agent such as Triton X-100, Tween-20.
Described protease inhibitor is a citric acid.
Protease inhibitor can be specific intestinal protease inhibitor, as aprotinin, Polycarbophil, Bowman-Berk inhibitor etc.It also can be " wide spectrum " intestinal protease inhibitor; as acetyl group glutamic acid, alanine, arginine, aspartic acid, aspartic acid, betanin, carnitine, carnosine, citrulline, sarcosine, glutamic acid, glycine, histidine, hydroxylysine, hydroxyproline, hypotaurine, isoleucine, leucine, lysine, methylhistidin and other aminoacid etc.; and comprise organic acid such as citric acid, acetic acid.
The optimum activity of intestinal protease all in alkaline range, if reduce pH in the zone of drug release, then can effectively suppress intestinal protease degraded Pramlintide and Ai Gelei peptide.The protease inhibitor of " wide spectrum " is any pH value in the intestinal that can effectively reduce after oral, human body is not had the chemical compound of toxic side effect.
The preparation method of the oral capsule preparation of treatment diabetes and obesity: help absorbent and protease inhibitor by the proportioning mix homogeneously Pramlintide or Ai Gelei peptide, intestinal, wrap up water-soluble capsule at mixture, and then deposited one deck enteric coated capsule.
The preparation method of the oral capsule preparation of treatment diabetes and obesity can also be: help absorbent by the proportioning mix homogeneously Pramlintide or Ai Gelei peptide and intestinal, with fluidized bed spraying rubbing method capsule liquid is sprayed on outside the mixture, make some Caplets, Caplet and protease inhibitor mixing are coated in the water-soluble capsule, outside water-soluble capsule, coat one deck enteric coated capsule then again.
The preparation method of the oral capsule preparation of treatment diabetes and obesity can also be: help absorbent by the proportioning mix homogeneously Pramlintide or Ai Gelei peptide and surplus, with fluidized bed spraying rubbing method capsule liquid is sprayed on outside the mixture, make some Caplets, help the mixture mixing of absorbent to be coated in the water-soluble capsule Caplet and protease inhibitor and part, outside water-soluble capsule, coat one deck enteric coated capsule then again.
What outer field enteric coated capsule adopted is soluble under the acid condition of gastric, but enters (pH is greater than 6) soluble capsule behind the intestinal.This class capsule has been widely used in oral medicine, therefore all can be used for this invention.This class material comprises cellulose O-phthalic acetate, hydroxypropyl emthylcellulose O-phthalic salt, hydroxypropyl methyl ethyl cellulose succinate, hydroxymethyl ethyl cellulose and methacrylic-methacrylic acid resin copolymer, acrylic resin L-30D-55 (Eudragit L30D-55) etc.
The present invention has changed peptide drug---the dosage form of Pramlintide and Ai Gelei peptide of treatment diabetes and obesity, and making double-deck capsular oral formulations is that internal layer is a medicine, and medicine is outward water-soluble capsule and enteric coated capsule successively.Double-deck capsular mechanism is: after taking; protective effect because of outer enteric coated capsule; owing to show acid in stomach is dirty; and enteric coated capsule does not dissolve under acid condition; therefore capsule can be complete, and to pass through stomach dirty; after entering intestinal; owing to show alkalescence in the intestinal; outer enteric coated capsule dissolving; time outer field water-soluble capsule dissolving is collapsed and is disengaged protease inhibitor, helps absorbent and albumen medicine then; protease inhibitor makes the pH value of intestinal inner region reduce to below 4 by 7～9, makes Pramlintide and Ai Gelei peptide under the help that helps absorbent, by intestinal absorption.Certainly, in order better to bring into play the drug effect of Pramlintide and Ai Gelei peptide, also can be made into the multilamellar capsule, elder generation is the albumen medicine and help the absorbent mix homogeneously, adopt spraying process that capsule liquid is sprayed on albumen medicine and the outside that helps the absorbent mixture, make Caplet earlier, and then be rolled in the water-soluble capsule with the protease inhibitor hybrid packet, coat one deck enteric coated capsule at last, make the multilamellar capsule, after capsule passes through stomach fully, in intestinal, at first discharge protease inhibitor like this, the zonal pH value of intestinal is reduced to below 4, last Caplet dissolving discharges the albumen medicine and helps absorbent, and at this moment the albumen medicine is under the help that helps absorbent, by intestinal absorption, further improved the utilization rate of albumen medicine.
Therapeutic dose of the present invention is metering with Pramlintide and Ai Gelei peptide active substance, for human body, and each consumption 1-40 microgram/kilogram, every day 2-3 time.
The present invention adopts animal experiment to observe bioavailability.Get 30 female Wistar rats, divide two groups to test oral capsule preparation of the present invention.Before carotid artery inserts sleeve pipe, female Wistar rats is anaesthetized.Import commensurability normal saline with a three-phase valve by this sleeve pipe blood sampling and each replenishing.By the abdominal cavity otch dosage form hydrotrope of the present invention is directly injected duodenum.The consumption of Pramlintide is 0.2 a milligram/rat, and the consumption of Ai Gelei peptide is 0.01 a milligram/rat, measures before injecting and 5,15,60,120 minutes blood sample.Calculate bioavailability, the results are shown in Table 1.
Table 1
| Experiment number | 1 | 2 | 3 | 4 | 5 |
| Pramlintide bioavailability (%) | 5.8 | 4.6 | 7.9 | 10.4 | 14.7 |
| Ai Gelei peptide bioavailability (%) | 6.7 | 7.7 | 9.5 | 11.6 | 15.9 |
By detection to blood sample, use capsule oral preparation of the present invention as can be known, Pramlintide and Ai Gelei peptide bioavailability can reach 5-15%.
Adopt the experiment similar to table 1, get in a small amount that blood carries out the experiment of blood glucose effect to rat, testing result sees Table 2 and table 3.This two table shows that peroral dosage form Pramlintide and Ai Gelei peptide have tangible blood sugar lowering effect.
Table 2, the blood glucose effect of Pramlintide 200 micrograms/rat
| Time (hour) | ?0 | 1 | 2 | ?4 |
| Normal saline plasma glucose (%) | ?100 | 110 | 95 | ?105 |
| Pramlintide plasma glucose (%) | ?100 | 85 | 50 | ?40 |
Table 3, the blood glucose effect of Ai Gelei peptide 10 micrograms/rat
| Time (hour) | ?0 | 1 | 2 | 4 |
| Normal saline plasma glucose (%) | ?100 | 105 | 90 | 110 |
| Ai Gelei peptide plasma glucose (%) | ?100 | 80 | 55 | 45 |
Carry out the effect test of obesity with following experiment: 18 male Sprague Dawley rats (average weight 380 grams) are divided into two groups, and one group is contrast (normal saline), and one group is medication.Medicine is made the soft gelatin capsule that can freshen food to the artificial regularly administration of rat by the inventive method.The results are shown in Table 4 and table 5.(providing in the administration scale of Pramlintide and Ai Gelei peptide)
Table 4, every not commensurability Pramlintide of rat is with the body weight change after 30 days
| Each consumption (microgram, twice of every day) | ?0 | 2 | 20 | 100 |
| Normal saline body weight change meansigma methods (gram) (after 30 days) | ?0 | 0 | 0 | 0 |
| Pramlintide body weight change meansigma methods (gram) (after 30 days) | ?0 | 0 | -13 | -18 |
Table 5, the not commensurability Chinese mugwort of every rat Gray peptide is with the body weight change after 50 days
| Each consumption (microgram, twice of every day) | ?0 | 0.1 | 1 | 5 |
| Normal saline body weight change meansigma methods (gram) (after 50 days) | ?0 | 0 | 0 | 0 |
| Ai Gelei peptide body weight change meansigma methods (gram) (after 50 days) | ?0 | 0 | -20 | -25 |
From table 4 and table 5 as can be known, take the present invention, can reduce body weight.
The invention has the beneficial effects as follows:
1, solved oral protein drug low absorptivity problem.Because outermost layer is an enteric coated capsule, does not dissolve at gastric because of outer enteric coated capsule oral back, and protection Pramlintide and Ai Gelei peptide medicine are not degraded by pepsin.Inferior skin is a water-soluble capsule, plays the effect of isolating protease inhibitor and enteric coated capsule.Capsule is complete dirty by stomach, enter intestinal after, outer enteric coated capsule at first dissolves, releases of bursting apart of outer successively then water-soluble capsule discharges Pramlintide or Ai Gelei peptide and protease inhibitor and helps absorbent.Pramlintide or Ai Gelei peptide under the protection of protease inhibitor, are effectively absorbed by intestinal under the help that helps absorbent.In addition for better utilization albumen medicine; make multiple structure again at medicine to internal layer; the medicine that is internal layer is made several Caplets; and then mix with protease inhibitor; protease inhibitor can effectively protect next step Pramlintide that discharges or Ai Gelei peptide not to be degraded by erepsin like this, and can help the intestinal absorption of next step Pramlintide that discharges and Ai Gelei peptide medicine simultaneously.And Pramlintide in the Caplet of multilamellar capsule preparations internal layer or Ai Gelei peptide with help absorbent to discharge synchronously.Help absorbent can improve the infiltration of Pramlintide or Ai Gelei peptide, improve the intestinal half-life at the intestinal mucus barrier layer, and increase Pramlintide and Ai Gelei peptide in absorption process in intestinal wall iuntercellular or intracellular transportation.
The present invention alleviated polypeptide and protide oral medicine at intestinal by the problem of proteasome degradation, increased polypeptide and the absorbance of protide medicine in intestinal simultaneously, Pramlintide and the oral medicine of Ai Gelei peptide can be reached in vivo lift treatment concentration.
Description of drawings:
Fig. 1 is the double-deck capsule structure sketch map of the embodiment of the invention 1;
Fig. 2 is the multilamellar capsule structure sketch map of the embodiment of the invention 2;
Fig. 3 is the multilamellar capsule structure sketch map of the embodiment of the invention 3;
Fig. 4 is preparation technology's flow chart of internal layer Caplet.
The specific embodiment: following illustration is for invention is described, is not the restriction invention.
Embodiment 1
As shown in Figure 1, a kind of oral capsule preparation for the treatment of diabetes and obesity, its structure is a double-decker, is medicine layer 1, water-soluble capsule 2 and enteric coated capsule 3 from inside to outside successively.The medicine layer is by albumen medicine, the mixture that helps absorbent and protease inhibitor to form.
Used albumen medicine is Pramlintide, help absorbent is that Deoxycholyltaurine and lauroyl carnitine, protease inhibitor are citric acids.
Preparation method is as follows:
1, with 0.1 gram Pramlintide lyophilisation product, 5 gram Deoxycholyltaurinies, 5 gram lauroyl carnitinies and the granular citric acid mix homogeneously of 40 grams, this amount is the dose of 100 unit dose of preparation.
2, technology is wrapped in the medicine of above-mentioned preparation in 100 water-soluble capsules uniformly routinely.Capsule can adopt in the prior art, any capsule material that may be dissolved in the water.
3, the preparation of enteric coated capsule.Above-mentioned capsule is inserted in the coating rotary apparatus.At the skin that sprays into above-mentioned water-soluble capsule more than 45 ℃, unit temp drops to 30 ℃ to 25 ℃ with enteric coated capsule liquid, finishes back air drying 2-3 days, the novel oral capsule preparation of the diabetes that can obtain medical treatment and obesity.This is a double-decker.
The way of enteric coated capsule liquid is as follows: weighing 100 gram acrylic resin L-30D-55 (EudragitL30D-55), add 82 gram water, and 3 gram triethyl group citrates and 7.6 gram Pulvis Talci melt mixing.
As shown in Figure 2, a kind of oral capsule preparation for the treatment of diabetes and obesity, its structure is a multiple structure, is medicine layer 1, water-soluble capsule 2 and enteric coated capsule 3 from inside to outside successively.The mixture that medicine layer 1 is made up of some Caplets 4 and protease inhibitor 5, described Caplet are to coat the albumen medicine in the capsule and helping absorbent.
Used albumen medicine is Pramlintide, help absorbent is that Deoxycholyltaurine and lauroyl carnitine, protease inhibitor are citric acids.
Preparation method is as follows:
1,0.2 gram Pramlintide polypeptide lyophilisation product, 5 gram Deoxycholyltaurinies and 5 gram lauroyl carnitinies are mixed, make the tiny capsule and pill of 100-200 micron with fluidized bed spraying rubbing method.Fig. 4 has shown the basic process of fluidized bed spraying rubbing method.Make Pramlintide with air-flow 11 earlier and help absorber blend (dry powder) to flow, reuse capsule liquid 10 is sprayed above fluidized bed, is wrapped in Pramlintide and the surface that helps absorber blend, forms Caplet 4.With Caplet 4 and the granular citric acid mix homogeneously of 50 grams made, this amount can prepare the capsule of 100 unit dose.
2, then routinely technology the mixture of mix homogeneously is wrapped in 100 water-soluble capsules.Capsule can adopt in the prior art, any capsule material that may be dissolved in the water.。
3, the preparation of enteric coated capsule.Above-mentioned capsule is inserted in the coating rotary apparatus.Enteric coated capsule liquid is being sprayed into above-mentioned water-soluble capsular skin more than 45 ℃, unit temp drops to 30 ℃ to 25 ℃, finishes back air drying 2-3 days, the novel oral capsule preparation of the diabetes that can obtain medical treatment and obesity.This is a multiple structure.
As shown in Figure 3, a kind of oral capsule preparation for the treatment of diabetes and obesity, its structure is a multiple structure, is medicine layer 1, water-soluble capsule 2 and enteric coated capsule 3 from inside to outside successively.The mixture that medicine layer 1 helps the mixture 6 of absorbent to form by some Caplets 4 and protease inhibitor and part, wherein, Caplet is to coat the albumen medicine in the capsule and surplus helps absorbent.
Used albumen medicine is Pramlintide, help absorbent is that Deoxycholyltaurine and lauroyl carnitine, protease inhibitor are citric acids.
Preparation method is as follows:
1,0.5 gram Pramlintide polypeptide lyophilisation product, 5 gram Deoxycholyltaurinies and 5 gram lauroyl carnitinies are mixed, make the tiny capsule and pill of 100-200 micron with fluidized bed spraying rubbing method.Fig. 4 has shown the basic process of fluidized bed spraying rubbing method.Make Pramlintide with air-flow 11 earlier and help absorber blend (dry powder) to flow, reuse capsule liquid 10 is sprayed above fluidized bed, is wrapped in Pramlintide and the surface that helps absorber blend, forms Caplet 4.It is even that the Caplet of making 4 and 60 is restrained granular citric acids and 2.5 gram Deoxycholyltaurinies and 2.5 gram lauroyl carnitine mixture 6, and this amount can prepare the capsule of 100 unit dose.
2, then routinely technology the mixture of mix homogeneously is wrapped in 100 water-soluble capsules.Capsule can adopt in the prior art, any capsule material that may be dissolved in the water.。
3, the preparation of enteric coated capsule.Above-mentioned capsule is inserted in the coating rotary apparatus.Enteric coated capsule liquid is being sprayed into above-mentioned water-soluble capsular skin more than 45 ℃, unit temp drops to 30 ℃ to 25 ℃, finishes back air drying 2-3 days, the novel oral capsule preparation of the diabetes that can obtain medical treatment and obesity.This is a multiple structure.
A kind of oral capsule preparation for the treatment of diabetes and obesity, its structure are double-decker, are medicine layer 1, water-soluble capsule 2 and enteric coated capsule 3 from inside to outside successively.The medicine layer is by the albumen medicine, helps the mixture of absorbent and protease inhibitor.
Used albumen medicine is the Ai Gelei peptide, help absorbent is that Deoxycholyltaurine and lauroyl carnitine, protease inhibitor are citric acids.
Preparation method is as follows:
1, with 0.01 gram Ai Gelei peptide lyophilisation product, 5 gram Deoxycholyltaurinies, 5 gram lauroyl carnitinies and the granular citric acid mix homogeneously of 40 grams, this amount is the dose of 100 unit dose of preparation.
2, technology is wrapped in the medicine of above-mentioned preparation in 100 water-soluble capsules uniformly routinely.Capsule can adopt in the prior art, any capsule material that may be dissolved in the water.
3, the preparation of enteric coated capsule.Above-mentioned capsule is inserted in the coating rotary apparatus.At the skin that sprays into above-mentioned water-soluble capsule more than 45 ℃, unit temp drops to 30 ℃ to 25 ℃ with enteric coated capsule liquid, finishes back air drying 2-3 days, the novel oral capsule preparation of the diabetes that can obtain medical treatment and obesity.This is a double-decker.
The way of enteric coated capsule liquid is as follows: weighing 100 gram acrylic resin L-30D-55 (EudragitL30D-55), add 82 gram water, and 3 gram triethyl group citrates and 7.6 gram Pulvis Talci melt mixing.
A kind of oral capsule preparation for the treatment of diabetes and obesity, its structure are multiple structure, are medicine layer 1, water-soluble capsule 2 and enteric coated capsule 3 from inside to outside successively.The mixture that medicine layer 1 is made up of some Caplets 4 and protease inhibitor 5, described Caplet are to coat the albumen medicine in the capsule and helping absorbent.
Used albumen medicine is the Ai Gelei peptide, help absorbent is that Deoxycholyltaurine and lauroyl carnitine, protease inhibitor are citric acids.
Preparation method is as follows:
1,0.002 gram Ai Gelei galanin peptide lyophilisation product, 1 gram Deoxycholyltaurine and 1 gram lauroyl carnitine are mixed, make the tiny capsule and pill of 100-200 micron with fluidized bed spraying rubbing method.The basic process of fluidized bed spraying rubbing method is: make the Ai Gelei peptide with air-flow earlier and help absorber blend (dry powder) to flow, reuse capsule liquid is sprayed above fluidized bed, is wrapped in Ai Gelei peptide and the surface that helps absorber blend, forms Caplet.With Caplet and the granular citric acid mix homogeneously of 30 grams made, this amount can prepare the capsule of 100 unit dose.
2, then routinely technology the mixture of mix homogeneously is wrapped in 100 water-soluble capsules.Capsule can adopt in the prior art, any capsule material that may be dissolved in the water.。
3, the preparation of enteric coated capsule.Above-mentioned capsule is inserted in the coating rotary apparatus.Enteric coated capsule liquid is being sprayed into above-mentioned water-soluble capsular skin more than 45 ℃, unit temp drops to 30 ℃ to 25 ℃, finishes back air drying 2-3 days, the novel oral capsule preparation of the diabetes that can obtain medical treatment and obesity.This is a multiple structure.
Embodiment 6
A kind of oral capsule preparation for the treatment of diabetes and obesity, its structure are multiple structure, are medicine layer 1, water-soluble capsule 2 and enteric coated capsule 3 from inside to outside successively.The mixture that medicine layer 1 helps the mixture 6 of absorbent to form by some Caplets 4 and protease inhibitor and part, described Caplet are to coat the albumen medicine in the capsule and partly helping absorbent.
Used albumen medicine is the Ai Gelei peptide, help absorbent is that Deoxycholyltaurine and lauroyl carnitine, protease inhibitor are citric acids.
Preparation method is as follows:
1,0.005 gram Ai Gelei galanin peptide lyophilisation product, 2 gram Deoxycholyltaurinies and 2 gram lauroyl carnitinies are mixed, make the tiny capsule and pill of 100-200 micron with fluidized bed spraying rubbing method.The basic process of fluidized bed spraying rubbing method is: make the Ai Gelei peptide with air-flow 11 earlier and help absorber blend (dry powder) to flow, reuse capsule liquid 10 is sprayed above fluidized bed, is wrapped in Ai Gelei peptide and the surface that helps absorber blend, forms Caplet 4.It is even that the Caplet made and the 40 granular citric acids of gram and 0.5 gram Deoxycholyltaurine and 0.5 gram lauroyl carnitine are mixed, and this amount can prepare the capsule of 100 unit dose.
2, then routinely technology the mixture of mix homogeneously is wrapped in 100 water-soluble capsules.Capsule can adopt in the prior art, any capsule material that may be dissolved in the water.。
3, the preparation of enteric coated capsule.Above-mentioned capsule is inserted in the coating rotary apparatus.Enteric coated capsule liquid is being sprayed into above-mentioned water-soluble capsular skin more than 45 ℃, unit temp drops to 30 ℃ to 25 ℃, finishes back air drying 2-3 days, the novel oral capsule preparation of the diabetes that can obtain medical treatment and obesity.This is a multiple structure.
Claims (8)
1. oral capsule preparation for the treatment of diabetes and obesity, it is characterized in that: described capsule preparations is double-deck capsule structure, is medicine layer, water-soluble capsule and enteric coated capsule from inside to outside successively;
The mixture that described medicine layer is made up of some Caplets and protease inhibitor; Wherein, Caplet is to coat the albumen medicine in the capsule and helping absorbent;
Described albumen medicine is Pramlintide or Ai Gelei peptide; The described absorbent that helps is one or both mixing of Deoxycholyltaurine or lauroyl carnitine; Described protease inhibitor is a citric acid.
2. according to the oral capsule preparation of described treatment diabetes of claim 1 and obesity, it is characterized in that: in the medicine layer, the albumen medicine, help the proportioning of absorbent and protease inhibitor to be: the albumen medicine is the 0.02-5.0 milligram, helping absorbent is the 20-150 milligram, protease inhibitor 300-600 milligram.
3. according to the oral capsule preparation of described treatment diabetes of claim 2 and obesity, it is characterized in that: the albumen medicine, help the proportioning of absorbent and protease inhibitor to be: albumen medicine 0.1-2.0 milligram; Helping absorbent is the 50-100 milligram, and protease inhibitor is the 400-500 milligram.
4. the preparation method of the oral capsule preparation of a claim 1 or 2 described treatment diabetes and obesity, it is characterized in that: with Pramlintide or Ai Gelei peptide with help absorbent by the proportioning mix homogeneously, with fluidized bed spraying rubbing method capsule liquid is sprayed on outside the mixture, make some Caplets, Caplet and protease inhibitor mixing are coated in the water-soluble capsule, outside water-soluble capsule, coat one deck enteric coated capsule then again.
5. oral capsule preparation for the treatment of diabetes and obesity, it is characterized in that: described capsule preparations is double-deck capsule structure, is medicine layer, water-soluble capsule and enteric coated capsule from inside to outside successively;
The mixture that described medicine layer helps the mixture of absorbent to form by some Caplets and protease inhibitor and part; Wherein, Caplet is to coat the albumen medicine in the capsule and surplus helps absorbent;
Described albumen medicine is Pramlintide or Ai Gelei peptide; The described absorbent that helps is one or both mixing of Deoxycholyltaurine or lauroyl carnitine; Described protease inhibitor is a citric acid.
6. according to the oral capsule preparation of described treatment diabetes of claim 5 and obesity, it is characterized in that: in the medicine layer, the albumen medicine, help the proportioning of absorbent and protease inhibitor to be: the albumen medicine is the 0.02-5.0 milligram, helping absorbent is the 20-150 milligram, protease inhibitor 300-600 milligram.
7. according to the oral capsule preparation of described treatment diabetes of claim 6 and obesity, it is characterized in that: the albumen medicine, help the proportioning of absorbent and protease inhibitor to be: albumen medicine 0.1-2.0 milligram; Helping absorbent is the 50-100 milligram, and protease inhibitor is the 400-500 milligram.
8. the preparation method of the oral capsule preparation of a claim 5 or 6 described treatment diabetes and obesity, it is characterized in that: help absorbent by the proportioning mix homogeneously Pramlintide or Ai Gelei peptide and surplus, with fluidized bed spraying rubbing method capsule liquid is sprayed on outside the mixture, make some Caplets, Caplet and protease inhibitor and part are helped the mixture mixing of absorbent, be coated in the water-soluble capsule, outside water-soluble capsule, coat one deck enteric coated capsule then again.
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| CN2008100108947A CN101548961B (en) | 2008-04-03 | 2008-04-03 | Novel oral capsule preparation for curing diabetes mellitus and obesity |
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| CN2008100108947A CN101548961B (en) | 2008-04-03 | 2008-04-03 | Novel oral capsule preparation for curing diabetes mellitus and obesity |
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| CN101548961B true CN101548961B (en) | 2011-05-04 |
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| CN102049042A (en) * | 2009-11-03 | 2011-05-11 | 付金坤 | Novel oral compound capsule preparation for treating diabetes and obesity |
| CN102283818A (en) * | 2010-06-20 | 2011-12-21 | 段明华 | Orally-administrated enteric capsule with polypeptide and protein medicaments and preparation method thereof |
| CN109602718A (en) * | 2018-12-24 | 2019-04-12 | 江苏辰星药业股份有限公司 | A kind of enteric plant soft capsule and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1270060A (en) * | 2000-03-16 | 2000-10-18 | 王登之 | Enteric insulin capsule for treating diabetes |
| CN1348369A (en) * | 1998-11-12 | 2002-05-08 | 史密丝克莱恩比彻姆有限公司 | Pharmaceutical composition for modified release of an insulin sensitiser and another antidiabetic agent |
| CN1933855A (en) * | 2003-12-26 | 2007-03-21 | 纳斯泰克制药公司 | Method of treatment of a metabolic disease using intranasal administration of exendin peptide |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1348369A (en) * | 1998-11-12 | 2002-05-08 | 史密丝克莱恩比彻姆有限公司 | Pharmaceutical composition for modified release of an insulin sensitiser and another antidiabetic agent |
| CN1270060A (en) * | 2000-03-16 | 2000-10-18 | 王登之 | Enteric insulin capsule for treating diabetes |
| CN1933855A (en) * | 2003-12-26 | 2007-03-21 | 纳斯泰克制药公司 | Method of treatment of a metabolic disease using intranasal administration of exendin peptide |
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