CN102940888B - A preparation method of drug-containing colon-targeted lecithin/pectin pellets - Google Patents
A preparation method of drug-containing colon-targeted lecithin/pectin pellets Download PDFInfo
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- CN102940888B CN102940888B CN201210448390.XA CN201210448390A CN102940888B CN 102940888 B CN102940888 B CN 102940888B CN 201210448390 A CN201210448390 A CN 201210448390A CN 102940888 B CN102940888 B CN 102940888B
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- pectin
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- 239000001814 pectin Substances 0.000 title claims abstract description 61
- 235000010987 pectin Nutrition 0.000 title claims abstract description 61
- 229920001277 pectin Polymers 0.000 title claims abstract description 61
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 title claims abstract description 29
- 239000000787 lecithin Substances 0.000 title claims abstract description 29
- 235000010445 lecithin Nutrition 0.000 title claims abstract description 29
- 229940067606 lecithin Drugs 0.000 title claims abstract description 29
- 239000003814 drug Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims description 11
- 229940079593 drug Drugs 0.000 title abstract description 15
- 239000008188 pellet Substances 0.000 title 1
- 239000012153 distilled water Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 11
- 239000000725 suspension Substances 0.000 claims abstract description 10
- 238000007127 saponification reaction Methods 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 7
- 229910021645 metal ion Inorganic materials 0.000 claims abstract description 6
- 238000001132 ultrasonic dispersion Methods 0.000 claims abstract description 3
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 229960000905 indomethacin Drugs 0.000 claims description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 235000010603 pastilles Nutrition 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims description 3
- FSQKKOOTNAMONP-UHFFFAOYSA-N acemetacin Chemical compound CC1=C(CC(=O)OCC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 FSQKKOOTNAMONP-UHFFFAOYSA-N 0.000 claims description 3
- 229960004892 acemetacin Drugs 0.000 claims description 3
- 229960004436 budesonide Drugs 0.000 claims description 3
- 229960001193 diclofenac sodium Drugs 0.000 claims description 3
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 3
- 229960000991 ketoprofen Drugs 0.000 claims description 3
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 claims description 3
- 229960004963 mesalazine Drugs 0.000 claims description 3
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 claims description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 2
- 229910001424 calcium ion Inorganic materials 0.000 claims description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- -1 iron ion Chemical class 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 238000007711 solidification Methods 0.000 claims description 2
- 230000008023 solidification Effects 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 8
- 230000008685 targeting Effects 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 238000012377 drug delivery Methods 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 3
- 239000003431 cross linking reagent Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 abstract 4
- 150000001455 metallic ions Chemical class 0.000 abstract 1
- 239000006187 pill Substances 0.000 abstract 1
- 239000012266 salt solution Substances 0.000 abstract 1
- 238000000967 suction filtration Methods 0.000 abstract 1
- 238000001647 drug administration Methods 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 3
- PYMYPHUHKUWMLA-UHFFFAOYSA-N 2,3,4,5-tetrahydroxypentanal Chemical compound OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000019399 Colonic disease Diseases 0.000 description 1
- 229920001688 coating polymer Polymers 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a targeted drug delivery method of pectin colon containing lecithin, which comprises the following steps that (1) pectin is added into distilled water to be stirred and dissolved, then a colloidal solution is obtained, an alkali solution is added for saponification, and then a pectin solution is obtained after stirring; (2) the lecithin is added into the pectin solution to be uniformly mixed, a drug which needs to be carried is added, and ultrasonic dispersion is performed to obtain a uniform suspension; (3) the suspension is slowly dropped in a divalent metal ion salt solution with the mass concentration of 1% to 6% for gel curing reaction, and then gel balls are obtained after dropping, standing and suction filtration; and (4) the gel balls are washed with distilled water and then dried at room temperature, and then a finished product is obtained. According to the targeted drug delivery method, the pectin is used as a skeletal material, metallic ions are used as a crosslinking agent, the lecithin component is added in a compound way, the release of the drug is effectively controlled before the drug reaches colons, and the colon targeting property of gel micro pills is increased.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to oral colon-target administration; More precisely, relate to a kind of medication taking pectin as framework material for medicine controlled releasing or oral colon-target administration.
Background technology
Colon targeting drug administration is mainly by drug delivery system, makes, after drug oral, not discharge in upper gi tract, drug conveying is started to disintegrate or loses and separate and discharge to human body ileocecus, in colon performance part or whole body therapeutic effect.Oral colon-target drug-delivery preparation is usually used in treating colonic diseases, as colitis, colon cancer etc., can make medicine directly discharge at diseased region, makes that medicine is more effective to play a role.
Pectin is a kind of natural macromolecule amylose, can be used as the carrier of medicine controlled releasing or oral colon-target administration.The enzymolysis type drug-supplying system that pectin makes is considered to location more accurately and reliably, and is not subject to the impact of individual variation.But the hydrophilic of pectin makes pectin base drug-supplying system easily swelling in environment and discharge in advance medicine in vivo.
In the past few years, in the time of design colon targeting drug administration system, take numerous methods to prevent that pectin base medicine from discharging in advance in upper gi tract.Pectin is by compound with other polymer, to improve hydrophobic performance; Pectin based system also can be coated by thin film or packaging technique the coating of slow release outward.The coating of different chemical composition can delay and the release of regulating drug at upper gi tract different parts, and the chemical composition of skeleton and coating polymer is to affect the key factor that colon specific drug discharges.
By retrieval, not yet find and the segmented intestine targeted relevant patent document of lecithin/pectin.
Summary of the invention
The object of the present invention is to provide a kind of pectin colon targeting drug administration method containing lecithin, this method is taking pectin as framework material, taking metal ion as cross-linking agent, by the compound lecithin fraction that adds, arrive antecolic release to control medicine, improving the segmented intestine targeted property of gel microsphere.
The object of the invention is to be achieved through the following technical solutions:
Containing a pectin colon targeting drug administration method for lecithin, step is:
(1) pectin is added to distilled water stirring and dissolving, form colloidal solution, add aqueous slkali to carry out saponification, stir and be made into pectin solution;
(2) in pectin solution, add lecithin, mix homogeneously, then add the medicine that needs carrier band, ultrasonic dispersion forms uniform suspension;
(3) above-mentioned suspension slowly being splashed into mass concentration is in 1% ~ 6% bivalent metal ion saline solution, carries out gel solidification reaction, after dripping afterwards place, sucking filtration, form gel ball;
(4) use distilled water wash gel ball, gained gel ball obtains finished product after being at room temperature dried.
And described pectin comprises hypo-methoxy pectin and hyper-methoxy pectin, high methoxyl carries out saponification processing by alkali in advance, and alkali comprises sodium hydroxide, potassium hydroxide, sodium carbonate etc., and the addition of alkali is 2% ~ 20% of pectin quality.
And the mass ratio of described lecithin and pectin is 1:4 ~ 8:4.
And the medicine of described carrier band comprises indomethacin, ketoprofen, acemetacin, mesalazine, budesonide, diclofenac sodium, the mass ratio of itself and pectin is 1:1-1:8.
And described bivalent metal ion salt comprises hydrochlorate or the sulfate of calcium ion, zinc ion, iron ion.
Advantage of the present invention and good effect are:
1, the present invention adds lecithin can effectively reduce the swellability of pectin gel micropill, and the drug carrying ability of pectin gel micropill and the sustained release performance in simulated intestinal fluid are significantly improved.
2, the present invention is after compound lecithin, lecithin/pectin gel micropill cumulative release rate in small intestinal simulated solution is starkly lower than simple pectin gel micropill, in small intestinal simulated solution, 8h cumulative release rate is reduced to below 5%, and lecithin/pectin gel micropill is also better than simple pectin gel micropill at high temperature and illumination stability inferior.
Detailed description of the invention
Below by detailed description of the invention, the present invention is described further, but should not be construed as limitation of the invention.Those of ordinary skill in the art, according to technique scheme, can also make amendment, replacement, the change of various ways.All amendments of doing based on above-mentioned technological thought, replacement, change all belong to scope of the present invention.
The percentage ratio of following each embodiment is mass percent.
The crude drug of following each embodiment, only taking indomethacin as example, can be ketoprofen, acemetacin, mesalazine, budesonide, diclofenac sodium in addition.
Embodiment 1:
A kind of preparation method of the lecithin/calcium pectinate micropill containing indomethacin: step is:
(1) pectin 0.4g, adds 8ml distilled water, forms colloidal solution, adds the NaOH solution saponification of 2ml 3%, stirs and is made into pectin solution;
(2) add 0.3g lecithin, stir it is mixed homogeneously with pectin solution, indomethacin crude drug 0.1g is added in pectin solution, ultrasonic it is uniformly dispersed;
(3) this suspension is slowly splashed in 6% calcium chloride solution, carry out gelling curing reaction, placement after dripping completes, sucking filtration, form gel ball;
(4) above-mentioned gel ball distilled water wash 2 ~ 3 times, the dry finished product that obtains.
Embodiment 2:
A kind of preparation method of the lecithin/calcium pectinate micropill containing indomethacin: step is:
(1) pectin 0.4g, adds 8ml distilled water, forms colloidal solution, adds the NaOH solution saponification of 2ml 2%, stirs and is made into pectin solution;
(2) add 0.3g lecithin, stir it is mixed homogeneously with pectin solution, indomethacin crude drug 0.15g is added in pectin solution, ultrasonic it is uniformly dispersed;
(3) this suspension is slowly splashed in 6% calcium chloride solution, carry out gelling curing reaction, placement after dripping completes, sucking filtration, form gel ball;
(4) above-mentioned gel ball distilled water wash 2 ~ 3 times, the dry finished product that obtains.
Embodiment 3:
A preparation method that contains lecithin/pectin zinc micropill of indomethacin, step is:
(1) pectin 0.4g, adds 8ml distilled water, forms colloidal solution, adds the NaOH solution saponification of 2ml 2%, stirs and is made into pectin solution;
(2) add 0.3g lecithin, treat that it mixs homogeneously with pectin solution, indomethacin crude drug 0.1g is added in pectin solution, ultrasonic it is uniformly dispersed;
(3) suspension is slowly splashed in 5% liquor zinci chloridi, carry out gelling curing reaction, placement after dripping completes, sucking filtration, form gel ball;
(4) above-mentioned gel ball distilled water wash 2 ~ 3 times, the dry finished product that obtains.
Embodiment 4:
A preparation method that contains lecithin/pectin zinc micropill of indomethacin, step is:
(1) pectin 0.4g, adds 8ml distilled water, forms colloidal solution, adds the NaOH solution saponification of 2ml2%, stirs and is made into pectin solution.
(2) add 0.5g lecithin, treat that it mixs homogeneously with pectin solution, indomethacin crude drug 0.1g is added in pectin solution, ultrasonic it is uniformly dispersed;
(3) suspension is slowly splashed in 6% liquor zinci chloridi, carry out gelling curing reaction, placement after dripping completes, sucking filtration, form gel ball;
(4) above-mentioned gel ball distilled water wash 2 ~ 3 times, the dry finished product that obtains.
Claims (4)
1. a preparation method for lecithin/pectin micropill of pastille, is characterized in that: step is:
(1) pectin is added to distilled water stirring and dissolving, form colloidal solution, add aqueous slkali to carry out saponification, stir and be made into pectin solution;
(2) in pectin solution, add lecithin, mix homogeneously, then add the medicine that needs carrier band, ultrasonic dispersion forms uniform suspension;
(3) above-mentioned suspension slowly being splashed into mass concentration is in 1%～6% bivalent metal ion saline solution, carries out gel solidification reaction, after dripping afterwards place, sucking filtration, form gel ball;
(4) use distilled water wash gel ball, gained gel ball obtains finished product after being at room temperature dried;
The mass ratio of described lecithin and pectin is 1:4～8:4.
2. the preparation method of lecithin/pectin micropill of pastille according to claim 1, it is characterized in that: described pectin is selected from hypo-methoxy pectin and hyper-methoxy pectin, high methoxyl carries out saponification processing by alkali in advance, alkali is selected from sodium hydroxide, potassium hydroxide or sodium carbonate, and the addition of alkali is 2%～20% of pectin quality.
3. the preparation method of lecithin/pectin micropill of pastille according to claim 1, it is characterized in that: the medicine of described carrier band is selected from indomethacin, ketoprofen, acemetacin, mesalazine, budesonide or diclofenac sodium, the mass ratio of itself and pectin is 1:1-1:8.
4. the preparation method of lecithin/pectin micropill of pastille according to claim 1, is characterized in that: described bivalent metal ion salt is selected from hydrochlorate or the sulfate of calcium ion, zinc ion, iron ion.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210448390.XA CN102940888B (en) | 2012-11-12 | 2012-11-12 | A preparation method of drug-containing colon-targeted lecithin/pectin pellets |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210448390.XA CN102940888B (en) | 2012-11-12 | 2012-11-12 | A preparation method of drug-containing colon-targeted lecithin/pectin pellets |
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| Publication Number | Publication Date |
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| CN102940888A CN102940888A (en) | 2013-02-27 |
| CN102940888B true CN102940888B (en) | 2014-09-24 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104367588B (en) * | 2014-11-29 | 2017-02-22 | 山西医科大学 | Dexamethasone, pectin and zinc combined gel oral colon-specific drug delivery pellet |
| CN108851084B (en) * | 2018-06-06 | 2021-06-15 | 福建省农业科学院农业工程技术研究所 | Colon positioning micelle loaded with quercetin and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN86108429A (en) * | 1985-12-20 | 1988-01-20 | 沃纳-兰伯特公司 | Confectionary or Live Substance Delivery Systems |
| CN1284838A (en) * | 1998-01-08 | 2001-02-21 | 大塚食品株式会社 | Gelled foods and process for producing the same |
| CN1326784A (en) * | 2000-06-07 | 2001-12-19 | 张昊 | Colon-releasing oral biological preparation |
| CN1676164A (en) * | 2004-03-31 | 2005-10-05 | 张昊 | Colon positioned-release oral insulin self-micro emulsion formulation and capsule containing it |
-
2012
- 2012-11-12 CN CN201210448390.XA patent/CN102940888B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN86108429A (en) * | 1985-12-20 | 1988-01-20 | 沃纳-兰伯特公司 | Confectionary or Live Substance Delivery Systems |
| CN1284838A (en) * | 1998-01-08 | 2001-02-21 | 大塚食品株式会社 | Gelled foods and process for producing the same |
| CN1326784A (en) * | 2000-06-07 | 2001-12-19 | 张昊 | Colon-releasing oral biological preparation |
| CN1676164A (en) * | 2004-03-31 | 2005-10-05 | 张昊 | Colon positioned-release oral insulin self-micro emulsion formulation and capsule containing it |
Non-Patent Citations (6)
| Title |
|---|
| "Interactions between food components and drugs Part 8: Effect of pectins and bile acid preparations forming stable mixed micelles on transport of quinine in vitro";B. Fritzsch et al;《pharmazie》;20001231;第55卷(第1期);59-61 * |
| "不同离子交联果胶凝胶微丸溶胀及释药性质研究";张良珂等;《生物医学工程学杂志》;20091031;第26卷(第5期);1030-1033 * |
| "果胶基口服结肠靶向给药系统的研究进展";刘健等;《现代化工》;20110228;第31卷(第2期);25-28 * |
| B. Fritzsch et al."Interactions between food components and drugs Part 8: Effect of pectins and bile acid preparations forming stable mixed micelles on transport of quinine in vitro".《pharmazie》.2000,第55卷(第1期), |
| 刘健等."果胶基口服结肠靶向给药系统的研究进展".《现代化工》.2011,第31卷(第2期), |
| 张良珂等."不同离子交联果胶凝胶微丸溶胀及释药性质研究".《生物医学工程学杂志》.2009,第26卷(第5期), |
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