CN103319413B - Polaprezinc compound - Google Patents
Polaprezinc compound Download PDFInfo
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- CN103319413B CN103319413B CN201310227401.6A CN201310227401A CN103319413B CN 103319413 B CN103319413 B CN 103319413B CN 201310227401 A CN201310227401 A CN 201310227401A CN 103319413 B CN103319413 B CN 103319413B
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- polaprezinc
- zinc
- carnosine
- histidine
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Abstract
The invention provides a polaprezinc compound. Polaprezinc compound is an L-carnosine complex of zinc, and the chemical name is poly 2-(S)-[mu-[N <alpha> (3-aminoproionyl)-L-histidine (2-)-N<1>,N<2>,O:N <tau>]-zinc). L-carnosine is a dipeptide that consists of beta-phenylalanine and L-histidine, and is an anti-oxidant that can promote wound healing. The polaprezinc compound of the present invention can be rapidly absorbed in vivo and eliminated after single or multi-time drug-feeding; multi-time drug-feeding has no accumulation phenomenon. Within test dosage, the subject can bear better and no light or severe adverse events happen during the whole test process, which means the drug is safe and has good human body tolerance. The improvement rate of chief complaint ulcer is 94.44%.
Description
Technical field
The invention belongs to pharmaceutical technology sectors, relate to a kind of Polaprezinc compound particularly.
Background technology
Peptide ulceration is 4.57% at China's sickness rate, and mainly based on person between twenty and fifty, serious threat China workforce population, affects China's Economic development.
Peptide ulceration mainly because of smoking, drink, nervous, medicine irritation (as NAIDS) causes, its pathogenesis focuses on invasion and attack factor and defending factors therebetween unbalance at present, and the difference of individual neuroendocrine response and hereditary predisposition.Antiulcer drug is mainly divided into anti-invasion factor medicine and promotes defense factor medicine; the anti-invasion factor comprises antacid, acid suppression medicine as m receptor blocking agent, G receptor antagonist, histamine H2-receptor blocking agent and Proton pump inhibitor and antipepsin medicine, promotes that defense factor class cartridge bag is drawn together and promotes that mucus generates medicine, mucosa protective agent and improves mucous membrane blood circulation medicine.
Zinc L-carnosine is the N-BETA-Alanyl-L-histidine complex compound of zinc, its chemistry poly-2-(S)-[μ-[N by name
α(3-aminopropionyl)-L-Histidine (2-)-N
1, N
2, O:N
τ]-zinc].The dipeptides that N-BETA-Alanyl-L-histidine is made up of β-Phenylalanine and L-group ammonia, it is a kind of antioxidant.Zinc can promote wound healing.Zinc L-carnosine is the latest generation medicament for anti-gastric ulcer developed by Japanese Hamari new drug Industrial Co., Ltd, and it is first, and for clinical zinc compound, this medicine went on the market in Japan in 1994 with trade(brand)name Promac, and formulation is granule.
Experiment shows; zinc L-carnosine has anti-oxidant and membrane stabilizing action; thus keep stomach mucous membrane homeostasis; reach the effect of cytoprotective, it also can promote wound healing simultaneously, strengthens defense factor effect; reach the effect preventing and treating peptide ulceration; zinc L-carnosine has the effect significantly suppressing ulcer to peptide ulceration models such as water logging, acetic acid, AAPH gastric mucosa injurys, it also has mucoadhesive by force simultaneously, improves effect of gastric mucosal defense effect.
Summary of the invention
The object of the present invention is to provide a kind of Polaprezinc compound, its structure is poly-2-(S)-[μ-[N
α(3-aminopropionyl)-L-Histidine (2-)-N
1, N
2, O:N
τ]-zinc].
Above-mentioned Polaprezinc compound, its X-ray powder diffraction pattern is about 8.8 ± 0.2 at 2 θ, and there is characteristic peak at 17.5 ± 0.2 and 19.0 ± 0.2 places.
Above-mentioned Polaprezinc compound, its X-ray powder diffraction pattern is about 13.1 ± 0.2 at 2 θ, and there is characteristic peak at 15.6 ± 0.2 and 21.1 ± 0.2 places.
Above-mentioned Polaprezinc compound, has similar collection of illustrative plates with accompanying drawing 1.
Above-mentioned Polaprezinc compound, has similar collection of illustrative plates with accompanying drawing 2.
Another object of the present invention is to provide a kind of pharmaceutical composition, it comprises the above-claimed cpd of effective dose and pharmaceutically acceptable auxiliary material.
Accompanying drawing explanation
Fig. 1 is the x-ray diffractogram of powder of the compound of the embodiment of the present invention 1.
Fig. 2 is the differential thermal analysis collection of illustrative plates of the compound of the embodiment of the present invention 1.
Embodiment
In order to understand the present invention better, the present invention and advantage thereof will be described in detail and be illustrated by embodiments of the invention and experimental data below, but these embodiments being not limited to the present invention.
Embodiment 1
Phthalyl-N-BETA-Alanyl-L-histidine, add excessive hydrazine hydrate and Glacial acetic acid, N-BETA-Alanyl-L-histidine highly finished product are obtained by washing with alcohol after hydrazinolysis reaction, then sodium hydrate methanol solution is added, the zinc acetate dihydrate of 2 times of mol ratios, fully stirs, and separates out precipitation 20-25% washing with alcohol 3 times, obtain zinc L-carnosine finished product compound, total recovery 67.89%.Powder x-ray diffraction: use Cu-K radiation, the X-ray powder diffraction pattern of this compound is shown in accompanying drawing 1.Differential scanning calorimetric analysis: accompanying drawing 2 is shown in by the differential thermal analysis collection of illustrative plates of this compound.
Embodiment 2
1, prescription
2, preparation technology
1) process of supplementary material
Take the supplementary material of recipe quantity, zinc L-carnosine was pulverized 200 mesh sieves, N.F,USP MANNITOL, Steviosin and 30 POVIDONE K 30 BP/USP
3080 mesh sieves are crossed after pulverizing, for subsequent use;
2) premix
N.F,USP MANNITOL 40 mesh sieves are disperseed, gets Steviosin and part N.F,USP MANNITOL and carry out equivalent and progressively increase and mix 4 times, cross 80 mesh sieves, obtain mixture 1.; By 30 POVIDONE K 30 BP/USP
30add mixture 1., mix, obtain mixture 2.; By mixture 2., zinc L-carnosine and residue N.F,USP MANNITOL drops in Mixers with Multi-direction Movement, premix about 20 minutes;
3) granulation, drying
The pre-mixed drug powder of step 2 is added in efficient wet nodulizer, slowly adds 50% ethanolic soln, make softwood; Use Pendulargranulator, obtained softwood is granulated with 24 mesh sieves; Obtained wet granular is added in Hotaircirculatingoven, is dried to moisture≤1.0% in 55 ~ 65 DEG C;
4) screening, whole grain
Dried particle is used respectively 16 orders and 80 mesh sieve, collect the particle of more than below 16 mesh sieves and 80 mesh sieves; By the particles more than 16 orders whole grain of 18 mesh sieve, collect the particle of more than below 16 mesh sieves and 80 mesh sieves;
5) total mixed, packing
Zinc L-carnosine midbody particle obtained for step 4 is dropped in Mixers with Multi-direction Movement, total mixed about 10 minutes; Packing after the assay was approved, to obtain final product.
Embodiment 3
1, prescription
2, preparation technology
1) process of supplementary material
Take the supplementary material of recipe quantity, zinc L-carnosine was pulverized 200 mesh sieves, N.F,USP MANNITOL, Steviosin and 30 POVIDONE K 30 BP/USP
3080 mesh sieves are crossed after pulverizing, for subsequent use;
2) premix
N.F,USP MANNITOL 40 mesh sieves are disperseed, gets Steviosin and part N.F,USP MANNITOL and carry out equivalent and progressively increase and mix 4 times, cross 80 mesh sieves, obtain mixture 1.; By 30 POVIDONE K 30 BP/USP
30add mixture 1., mix, obtain mixture 2.; By mixture 2., zinc L-carnosine and residue N.F,USP MANNITOL drops in Mixers with Multi-direction Movement, premix about 20 minutes;
3) granulation, drying
The pre-mixed drug powder of step 2 is added in efficient wet nodulizer, slowly adds 50% ethanolic soln, make softwood; Use Pendulargranulator, obtained softwood is granulated with 24 mesh sieves; Obtained wet granular is added in Hotaircirculatingoven, is dried to moisture≤1.0% in 55 ~ 65 DEG C;
4) screening, whole grain
Dried particle is used respectively 16 orders and 80 mesh sieve, collect the particle of more than below 16 mesh sieves and 80 mesh sieves; By the particles more than 16 orders whole grain of 18 mesh sieve, collect the particle of more than below 16 mesh sieves and 80 mesh sieves;
5) total mixed, packing
Zinc L-carnosine midbody particle obtained for step 4 is dropped in Mixers with Multi-direction Movement, total mixed about 10 minutes; Packing after the assay was approved, to obtain final product.
The clinical trial of test example-zinc L-carnosine granule of the present invention
For studying the dynamic change characteristic of zinc L-carnosine granule of the present invention (embodiment 2) absorption in healthy human body, distribution and elimination (metabolism and excretion), we have carried out the pharmacokinetic of multiple dosing to it.Multiple dosing: experimenter is morning and take 75mg medicine with 250ml warm water just before going to bed, gives about 13 times continuously.Sample number is 36 examples, and men and women half and half.After zinc L-carnosine particle (embodiment 2) single and multiple dosing, absorb in vivo rapidly, eliminate very fast; Multiple dosing is without cumulative appearance.Under test dose, experimenter all can better tolerate, and slight adverse events does not occur whole process of the test, and also do not have serious adverse events to occur, safety of medicine is described, human tolerance is good.Main suit's ulcer improvement rate 94.44%.
Claims (4)
1. a crystal formation for Polaprezinc compound, it is characterized in that its X-ray powder diffraction is 8.8 ± 0.2,17.5 ± 0.2 at 2 θ, there is characteristic peak at 19.0 ± 0.2,13.1 ± 0.2,15.6 ± 0.2 and 21.1 ± 0.2 places.
2. the crystal formation of Polaprezinc compound according to claim 1, is characterized in that having the collection of illustrative plates identical with accompanying drawing 1.
3. the crystal formation of Polaprezinc compound according to claim 1, is characterized in that having the collection of illustrative plates identical with accompanying drawing 2.
4. a pharmaceutical composition, is characterized in that the crystal formation of the Polaprezinc compound described in any one of claim 1-3 comprising effective dose and pharmaceutically acceptable auxiliary material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310227401.6A CN103319413B (en) | 2013-06-08 | 2013-06-08 | Polaprezinc compound |
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|---|---|---|---|
| CN201310227401.6A CN103319413B (en) | 2013-06-08 | 2013-06-08 | Polaprezinc compound |
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| CN103319413A CN103319413A (en) | 2013-09-25 |
| CN103319413B true CN103319413B (en) | 2015-02-04 |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105899520B (en) * | 2014-02-10 | 2018-07-10 | 株式会社德山 | The manufacturing method of purified containing crystallinity L-Car-Zn complex compound |
| CN106913859B (en) * | 2015-12-25 | 2021-05-11 | 中美华世通生物医药科技(武汉)股份有限公司 | Pharmaceutical composition and preparation method thereof |
| CN110314149B (en) * | 2016-10-17 | 2021-04-02 | 吉林省博大伟业制药有限公司 | Poly-pregnen-zinc tablet and preparation process thereof |
| CN111051289A (en) * | 2017-09-05 | 2020-04-21 | 株式会社德山 | Protected L-carnosine derivative, L-carnosine and method for producing crystalline L-carnosine zinc complex |
| KR102015516B1 (en) * | 2017-09-18 | 2019-08-28 | 하나제약 주식회사 | Wet granulation tablets with improved stability and method for preparing the same |
| CN111196837B (en) * | 2018-11-20 | 2023-07-28 | 皕达生物科技(上海)有限公司 | Preparation method of polyprenone and polyprenone preparation |
| CN113769059B (en) * | 2021-09-10 | 2024-02-13 | 北京鑫开元医药科技有限公司 | Poly (zinc prasugrel) granule and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5238931A (en) * | 1990-07-06 | 1993-08-24 | Zeria Pharmaceutical Co., Ltd. | Inflammatory bowel disease preventive and curative agent containing zinc l-carnosine salt as active ingredient |
| CN1857715A (en) * | 2006-03-23 | 2006-11-08 | 恩泰柯数码科技（北京）有限公司 | Cirrhosis treating medicine |
| JP2011001324A (en) * | 2009-06-22 | 2011-01-06 | Sawai Pharmaceutical Co Ltd | Polaprezinc-containing orally disintegrating tablet |
| CN103120646A (en) * | 2011-11-21 | 2013-05-29 | 四川海思科制药有限公司 | Polaprezinc granules and preparation method thereof |
-
2013
- 2013-06-08 CN CN201310227401.6A patent/CN103319413B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5238931A (en) * | 1990-07-06 | 1993-08-24 | Zeria Pharmaceutical Co., Ltd. | Inflammatory bowel disease preventive and curative agent containing zinc l-carnosine salt as active ingredient |
| CN1857715A (en) * | 2006-03-23 | 2006-11-08 | 恩泰柯数码科技（北京）有限公司 | Cirrhosis treating medicine |
| JP2011001324A (en) * | 2009-06-22 | 2011-01-06 | Sawai Pharmaceutical Co Ltd | Polaprezinc-containing orally disintegrating tablet |
| CN103120646A (en) * | 2011-11-21 | 2013-05-29 | 四川海思科制药有限公司 | Polaprezinc granules and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| The antioxidant properties of a novel zinc-carnosine chelate compound, N-(3-aminopropionyi)-t.-histidinato zinc;Toshikazu Yoshikawa 等;《Biochimica et Biophysica Acta(BBA)-General Subjiects》;19911114;第1115卷(第1期);第15-22页 * |
| 聚普瑞锌的合成;张清彦;《化学工程与装备》;20100515(第5期);第18-19页 * |
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Address after: The 856000 Tibet autonomous region in southern area of Zedang town Xiang Qu Road No. 8 Patentee after: Haisike Pharmaceutical Group Limited by Share Ltd Address before: The 856000 Tibet autonomous region in southern area of Zedang town Xiang Qu Road No. 8 Patentee before: Tibet Haisco Pharmaceutical Group Co., Ltd. |
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