CN105055444A - Pantoprazole sodium composition for treating gastric diseases - Google Patents
Pantoprazole sodium composition for treating gastric diseases Download PDFInfo
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- CN105055444A CN105055444A CN201510607767.5A CN201510607767A CN105055444A CN 105055444 A CN105055444 A CN 105055444A CN 201510607767 A CN201510607767 A CN 201510607767A CN 105055444 A CN105055444 A CN 105055444A
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- sodium
- pantoprazole
- pantoprazole sodium
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Abstract
The invention discloses a pantoprazole sodium composition for treating gastric diseases, belonging to the technical field of medicines. The composition is prepared from pantoprazole sodium and sodium chloride, wherein pantoprazole sodium is a crystal. An X-ray powder diffraction pattern obtained through measurement by using a Cu-Kalpha ray is shown in a drawing 1 in the specification. A new crystal form of pantoprazole sodium provided by the invention is different from the crystal structure of the prior art. Through experimental verification, the compound in the new crystal form has high purity, good flowability and stability and low impurity content, has low possibility of moisture absorption and is safe and reliable to apply clinically. Powder injections prepared by utilizing the compound in the new crystal form have good stability after undergoing compatibility with solvents, have low content of insoluble particles and are very suitable to apply clinically.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine pantoprazole composition of sodium for the treatment of gastropathy.
Background technology
Pantoprazole Sodium is proton pump inhibitor, the final step that gastric acid inhibitory produces by two site covalent bond of the H+-K+ATP enzyme system with parietal cell.This effect be dose dependent and make basis and stimulation state under gastric acid secretion all suppressed.The combination of H+-K+ATP enzyme can cause its anti-gastric acid secretion effect lasts more than 24 hours.Pantoprazole Sodium is the proton pump inhibitor of the 3rd listing after omeprazole and lansoprazole.Due to the substituted radical of Pantoprazole Sodium on pyridine ring and benzimidazole ring and omeprazole and lansoprazole different, thus determine its difference at biochemical, pharmacokinetics and pharmacological property, make it have stronger selectivity and specificity.
In prior art, for crystal formation and the hydrate of Pantoprazole Sodium, there is many research:
Patent application 02109182.X relates to anti-peptic ulcer medicine (±) 5-difluoro-methoxy-[[(3; 4-dimethoxy-2-pyridinyl) methyl] sulfinyl] left-handed (-) of-1H-benzimidazole and the salt of dextrorotation (+) enantiomer, i.e. S (-) pantoprazole potassium, sodium, magnesium, calcium, zinc salt R (+) pantoprazole potassium, sodium, magnesium, calcium, zinc salt.Additionally provide a kind of new preparation process of S (-) pantoprazole and R (+) pantoprazole, with chloroform or acetonitrile as solvents, under Sharpless reagent exists, carry out chiral oxidization obtain, be obtained by reacting with potassium hydroxide, potassium carbonate etc.
ZL201110228921.X discloses a kind of compound of pantoprazole sodium, this compound of pantoprazole sodium is crystal, and in the X-ray powder diffraction pattern using the measurement of Cu-K alpha ray to obtain, characteristic peak is 12.5 °, 12.6 °, 13.2 °, 16.2 °, 17.3 ° displays at 2 θ.
ZL201210306449.1 relates to a kind of pantoprazole sodium crystal, adopt X-diffraction powder diffraction, its collection of illustrative plates is followed successively by 9.5 °, 10.4 °, 11.6 °, 13.1 °, 13.8 °, 14.2 °, 15.0 °, 15.3 °, 15.9 °, 16.5 °, 17.5 °, 18.0 ° and 18.2 ° with the characteristic peak that 2 θ angles represent.
ZL201310093503.3 Pantoprazole Sodium crystalline compounds, pharmaceutical composition and preparation method thereof, the invention provides a kind of new Pantoprazole Sodium crystalline compounds, its pharmaceutical preparation particularly enteric coated capsule, and their preparation method, the chemical stability of Pantoprazole Sodium crystalline compounds of the present invention is better, dissolubility is more excellent, improve Drug safety, be beneficial to the long term storage of medicine, for clinical drug application provides safety guarantee, but the dissolution of the enteric coated capsule preparation of the mobility of its Pantoprazole Sodium crystalline compounds and preparation thereof, stability is unsatisfactory.
In order to improve the performance of Pantoprazole Sodium further, the present invention develops a kind of Pantoprazole Sodium noval chemical compound, finds through test, this crystal compound purity is high, good fluidity, good stability, impurity content is low, not easily moisture absorption, clinical practice is safe and reliable, utilizes the injectable powder that this crystal compound is obtained, good stability, good with solvent compatibility rear stability, particulate matter content is extremely low, is very suitable for clinical practice.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of medicine pantoprazole composition of sodium for the treatment of gastropathy.
In order to complete object of the present invention, the technical scheme of employing is:
Treat a medicine pantoprazole composition of sodium for gastropathy, consisting of of described compositions: Pantoprazole Sodium 1 weight portion, sodium chloride 0.04-0.08 weight portion; Described Pantoprazole Sodium is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
Preferably, consisting of of described pantoprazole composition of sodium: Pantoprazole Sodium 1 weight portion, sodium chloride 0.05-0.07 weight portion.
Preferably, consisting of of described pantoprazole composition of sodium: Pantoprazole Sodium 1 weight portion, sodium chloride 0.06 weight portion.
Preferably, the dosage form of described pantoprazole composition of sodium is injection, and the preparation method of described injection comprises the following steps:
(1) take pantoprazole sodium crystal and sodium chloride in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
The preparation method of the pantoprazole sodium crystal in described compositions comprises the following steps:
(1) ethanol, N, N-dimethyl formamide are mixed with mixed solvent, the volume ratio of ethanol, N, N-dimethyl formamide is 2:1;
(2) get pantoprazole sodium, the volume being dissolved in step (1) is in the mixed solvent of the ethanol of 6 times of Pantoprazole Sodium weight, N, N-dimethyl formamide, is warming up to 35 DEG C, is stirred to whole dissolving, obtain pantoprazole sodium solution;
(3) under the condition of low whipping speed 560r/min, the pantoprazole sodium solution of step (2) being joined volume is in the isoamyl alcohol of 5 times of Pantoprazole Sodium weight, mixing, forms suspension, is cooled to-10 DEG C with the speed of 10 DEG C/min;
(4) carry out sucking filtration, washing leaching cake, then by filter cake vacuum drying, obtain crystalline powder, be described compound of pantoprazole sodium.
The polymorphism of solid chemical is the natural phenomena that a kind of general material exists, this phenomenon refers to that a kind of solid chemical can exist 2 kinds or two or more crystal form state, be also called the polymorphic state of material, the polymorphic state of material is also referred to as " allomorphism " phenomenon.Although its chemical nature of allomorphous solid matter is identical, its physicochemical property may be different.For " allomorphism medicine " that physicochemical property is different, also can show the curative effect of different disease preventing and treating clinically, directly affect application and the clinical effectiveness of medicine.
The present invention is by the precise controlling to crystallization condition, and prepared a kind of pantoprazole sodium novel crystal form unlike the prior art, the X-ray powder diffraction pattern of this pantoprazole sodium crystal unlike the prior art.Simultaneously due to the ins and outs of this crystal formation, find through test, this crystal compound purity is high, good fluidity, good stability, impurity content is low, not easily moisture absorption, clinical practice is safe and reliable, utilize the injectable powder that this crystal compound is obtained, good stability, good with solvent compatibility rear stability, particulate matter content is extremely low, is very suitable for clinical practice.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the pantoprazole sodium crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
Detailed description of the invention
Below by specific embodiment, summary of the invention of the present invention is described in further detail, but does not therefore limit content of the present invention.
embodiment 1:the preparation of pantoprazole sodium crystal
(1) ethanol, N, N-dimethyl formamide are mixed with mixed solvent, the volume ratio of ethanol, N, N-dimethyl formamide is 2:1;
(2) get pantoprazole sodium, the volume being dissolved in step (1) is in the mixed solvent of the ethanol of 6 times of Pantoprazole Sodium weight, N, N-dimethyl formamide, is warming up to 35 DEG C, is stirred to whole dissolving, obtain pantoprazole sodium solution;
(3) under the condition of low whipping speed 560r/min, the pantoprazole sodium solution of step (2) being joined volume is in the isoamyl alcohol of 5 times of Pantoprazole Sodium weight, mixing, forms suspension, is cooled to-10 DEG C with the speed of 10 DEG C/min;
(4) carry out sucking filtration, washing leaching cake, then by filter cake vacuum drying, obtain crystalline powder, be described compound of pantoprazole sodium.
The X-ray powder diffraction pattern that the pantoprazole sodium crystal prepared uses the measurement of Cu-K alpha ray to obtain as shown in Figure 1.
embodiment 2:the preparation of pantoprazole composition of sodium
Consist of: pantoprazole sodium crystal 1 weight portion prepared by the present invention, sodium chloride 0.04 weight portion.
Preparation method is:
(1) take pantoprazole sodium crystal and sodium chloride in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 3:the preparation of pantoprazole composition of sodium
Consist of: pantoprazole sodium crystal 1 weight portion prepared by the present invention, sodium chloride 0.05 weight portion.
Preparation method is:
(1) take pantoprazole sodium crystal and sodium chloride in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 4:the preparation of pantoprazole composition of sodium
Consist of: pantoprazole sodium crystal 1 weight portion prepared by the present invention, sodium chloride 0.06 weight portion.
Preparation method is:
(1) take pantoprazole sodium crystal and sodium chloride in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 5:the preparation of pantoprazole composition of sodium
Consist of: pantoprazole sodium crystal 1 weight portion prepared by the present invention, sodium chloride 0.07 weight portion.
Preparation method is:
(1) take pantoprazole sodium crystal and sodium chloride in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 6:the preparation of pantoprazole composition of sodium
Consist of: pantoprazole sodium crystal 1 weight portion prepared by the present invention, sodium chloride 0.08 weight portion.
Preparation method is:
(1) take pantoprazole sodium crystal and sodium chloride in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
experimental example 1:mobility is tested
Pantoprazole Sodium crystalline compounds prepared by reference examples 1:ZL201310093503.3 embodiment 1
The mobility of this experimental example to the compound of pantoprazole sodium of the embodiment of the present invention 1 and reference examples 1 compound detects, adopt fixed funnel method, funnel is placed in the suitable height on graph paper, compound of pantoprazole sodium is freely flowed down from bell mouth, until the cone top formed contacts with bell mouth, measure hypotenuse and the horizontal angle (θ angle of repose) of compound of pantoprazole sodium accumulation horizon, experimental result is as shown in the table.
Table 1 mobility experimental result
From interpretation, the mobility of the compound of pantoprazole sodium that the embodiment of the present invention 1 prepares obviously is better than reference examples 1.
test example 2:stability test
The Pantoprazole Sodium that Example 2-4 is obtained, under high temperature 40 DEG C, relative humidity 75% ± 5% condition 6 months, carry out accelerated test investigation, result was as following table:
Table 2 accelerated test investigates result
From above result, impurity content of the present invention is low, and accelerated test is after 6 months, and the sample indices of embodiment of the present invention 2-4 and related substance significant change do not occur, and the good stability of the pantoprazole sodium injection that the present invention obtains is described.Identical test is carried out to other embodiments, has obtained similar result of the test.
Claims (5)
1. treat a medicine pantoprazole composition of sodium for gastropathy, it is characterized in that: described compositions is by Pantoprazole Sodium 1 weight portion, and sodium chloride 0.04-0.08 weight portion forms; Described Pantoprazole Sodium is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
2. the medicine pantoprazole composition of sodium for the treatment of gastropathy according to claim 1, is characterized in that: described compositions is by Pantoprazole Sodium 1 weight portion, and sodium chloride 0.05-0.07 weight portion forms.
3. the medicine pantoprazole composition of sodium for the treatment of gastropathy according to claim 2, is characterized in that: described compositions is by Pantoprazole Sodium 1 weight portion, and sodium chloride 0.06 weight portion forms.
4. the medicine pantoprazole composition of sodium of the treatment gastropathy according to any one of claim 1-3, is characterized in that, the dosage form of described pantoprazole composition of sodium is injection, and the preparation method of described injection comprises the following steps:
(1) take pantoprazole sodium crystal and sodium chloride in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
5. the medicine pantoprazole composition of sodium for the treatment of gastropathy according to claim 1, is characterized in that, the crystal preparation method of described Pantoprazole Sodium is:
(1) ethanol, N, N-dimethyl formamide are mixed with mixed solvent, the volume ratio of ethanol, N, N-dimethyl formamide is 2:1;
(2) get pantoprazole sodium, the volume being dissolved in step (1) is in the mixed solvent of the ethanol of 6 times of Pantoprazole Sodium weight, N, N-dimethyl formamide, is warming up to 35 DEG C, is stirred to whole dissolving, obtain pantoprazole sodium solution;
(3) under the condition of low whipping speed 560r/min, the pantoprazole sodium solution of step (2) being joined volume is in the isoamyl alcohol of 5 times of Pantoprazole Sodium weight, mixing, forms suspension, is cooled to-10 DEG C with the speed of 10 DEG C/min;
(4) carry out sucking filtration, washing leaching cake, then by filter cake vacuum drying, obtain crystalline powder, be described compound of pantoprazole sodium.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510607767.5A CN105055444A (en) | 2015-09-23 | 2015-09-23 | Pantoprazole sodium composition for treating gastric diseases |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510607767.5A CN105055444A (en) | 2015-09-23 | 2015-09-23 | Pantoprazole sodium composition for treating gastric diseases |
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| CN105055444A true CN105055444A (en) | 2015-11-18 |
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| CN201510607767.5A Withdrawn CN105055444A (en) | 2015-09-23 | 2015-09-23 | Pantoprazole sodium composition for treating gastric diseases |
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2015
- 2015-09-23 CN CN201510607767.5A patent/CN105055444A/en not_active Withdrawn
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Application publication date: 20151118 |