CN108721598B - Preparation method of oxytocin raw material, pharmaceutical composition and preparation thereof - Google Patents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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Abstract
The invention belongs to the technical field of biological medicines, and particularly relates to a preparation method of a oxytocin raw material, a pharmaceutical composition and a preparation thereof, wherein the pharmaceutical composition comprises the following raw and auxiliary materials: oxytocin raw material, L-glutamic acid and glycine; the method adopts 1-butanol as a solvent, after dissolving a oxytocin crude product, adding isopropanol and cyclohexanol in a certain proportion, cooling to a certain temperature, precipitating, and repeating the operation to obtain a new oxytocin raw material, wherein the raw material is low in impurity content and high in stability; the oxytocin raw material obtained by the purification method is added with a certain proportion of L-glutamic acid and glycine to prepare the freeze-dried powder injection, and stability research shows that the powder injection obtained by the method has more excellent quality.
Description
Technical Field
The invention belongs to the technical field of biological medicines. In particular to a preparation method of oxytocin raw material, a pharmaceutical composition and a preparation thereof.
Background
Oxytocin (OT) was discovered in 1895 as a nonapeptide amide having a disulfide bond, also known as oxytocin, a mammalian hormone, which is secreted mainly from the neurosecretory large cell system of the supraoptic nucleus and the paraventricular nucleus of the hypothalamus, released into the blood from the posterior pituitary and reaches the distant organs along the blood circulation to exert its effects, is widely used clinically for induction of labor, induction of labor and prevention of massive hemorrhage caused by uterine hypodynamia after childbirth, and is the only approved drug by the FDA in the united states for clinical induction of labor at present. The molecular weight of the composite is 1007.2Da, the molecular formula is C43H66N12O12S2, the isoelectric point is 7.7, the composite is easily soluble in water, soluble in acetone, butanol and dilute acetic acid, insoluble in diethyl ether and petroleum ether, the dry product is stable, the pH value is 3.8-4.4, and the composite is stable in an acidic solution and unstable in an alkaline solution. The production of the oxytocin for early medicine adopts a mode of extracting from animal posterior pituitary tissue, has the safety problems of virus inactivation, allergen removal, pyrogen removal and the like, and the extract has an analogue with a structure which is difficult to separate, namely the vasopressin. Since the first synthesis of oxytocin in 1969, more than 30 domestic oxytocin preparation manufacturers all adopt nonapeptide amide to synthesize oxytocin by a sodium-liquid ammonia elimination and condensation method, the purification process of the final product is complex, the product purity is low, the yield is low, and the method is one of the factors causing part of clinical adverse reactions. The main impurities in the chemically synthesized oxytocin crude product are some heteropeptides similar to the target polypeptide structure, such as diastereoisomers generated by amino acid racemization, deletion peptides generated when partial amino acids are not connected, broken peptides generated by peptide bond breakage, reduced open-loop peptides generated by incomplete oxidation and the like. Therefore, research and development of a new purification method for obtaining the oxytocin raw material with low impurity content and good stability and preparing the oxytocin preparation with excellent quality have important significance.
Disclosure of Invention
Based on the reasons, the applicant obtains a new method for purifying a oxytocin crude product through multiple creative tests, the method adopts 1-butanol as a solvent, after the oxytocin crude product is dissolved, isopropanol and cyclohexanol in a certain proportion are added, after the temperature is reduced to a certain temperature, precipitate is separated out, and the operation is repeated to obtain a new oxytocin raw material, wherein the raw material is low in impurity content and high in stability; the oxytocin raw material obtained by the purification method is added with a certain proportion of L-glutamic acid and glycine to prepare the freeze-dried powder injection, and stability research shows that the powder injection obtained by the method has more excellent quality.
The invention is realized by the following technical scheme.
A drug combination containing oxytocin comprises the following raw and auxiliary materials: oxytocin raw material, L-glutamic acid and glycine.
Wherein the weight ratio of the L-glutamic acid to the glycine is 50: 1: 3.3-4.5. .
Wherein the medicine is combined with raw and auxiliary materials to prepare injection.
The preparation method of the injection comprises the following steps:
adding glycine into water for injection, stirring, adding oxytocin raw material, adding L-glutamic acid, adding water for injection, filtering with 0.22 μm filter element, and packaging to obtain injection.
The preparation method of the oxytocin raw material comprises the following steps:
adding 1-butanol into a oxytocin crude product, heating to 30-40 ℃, adding isopropanol and cyclohexanol, cooling to 5-10 ℃, standing for 12-24 hours, filtering, washing a filter cake with isopropanol, adding 1-butanol to dissolve completely, adding isopropanol and cyclohexanol, cooling to 0-5 ℃, standing for 12-24 hours, filtering, washing the filter cake with isopropanol, and freeze-drying to obtain the oxytocin raw material.
Wherein the weight ratio of the oxytocin crude product to the 1-butanol is 1: 3-5.
Wherein the weight ratio of the oxytocin crude product to the isopropanol and the cyclohexanol is 1: 10-20: 0.3-0.8.
The invention aims to:
(1) the oxytocin crude product is dissolved by 1-butanol, isopropanol and cyclohexanol are added, precipitate is separated out at low temperature, and repeated operation is carried out to obtain the oxytocin raw material with a new crystal form.
(2) The invention is based on oxytocin raw material obtained by the purification method of the invention, and is compatible with auxiliary materials with a certain proportion: glycine, L-glutamic acid, glycine and L-glutamic acid in a certain proportion are used as an excipient, a protective agent, a pH regulator and the like.
(3) The raw materials and the preparation obtained by the invention are finished according to the consistency evaluation requirement, and have more excellent product quality.
Detailed Description
The present invention is further described in the following description of the specific embodiments, which is not intended to limit the invention, but various modifications and improvements can be made by those skilled in the art according to the basic idea of the invention, within the scope of the invention, as long as they do not depart from the basic idea of the invention.
The oxytocin crude product disclosed by the invention is purchased from Shenzhen Hanyu pharmaceutical industry, Limited, the purchase date is 2017, 12 months and 26 days, and the content of the oxytocin crude product is 83.4%.
Preparation examples
Example 1
Taking 1000g of oxytocin crude product, adding 3703.7mL (3000g) of 1-butanol, heating to 30 ℃, adding 12730.7mL (10000g) of isopropanol and 311.7mL (300g) of cyclohexanol, cooling to 5 ℃, standing for 12 hours, filtering, washing a filter cake with isopropanol, then adding 3703.7mL (3000g) of 1-butanol to dissolve completely, adding 12730.7mL (10000g) of isopropanol and 311.7mL (300g) of cyclohexanol, cooling to 0 ℃, standing for 12 hours, filtering, washing the filter cake with isopropanol, and freeze-drying to obtain 783.9g of oxytocin raw material.
Example 2
Taking 1000g of oxytocin crude product, adding 6172.8mL (5000g) of 1-butanol, heating to 40 ℃, adding 25461.5mL (20000g) of isopropanol and 831.3mL (800g) of cyclohexanol, cooling to 10 ℃, standing for 24 hours, filtering, washing a filter cake with isopropanol, then adding 6172.8mL (5000g) of 1-butanol to dissolve completely, adding 25461.5mL (20000g) of isopropanol and 831.3mL (800g) of cyclohexanol, cooling to 5 ℃, standing for 24 hours, filtering, washing the filter cake with isopropanol, and freeze-drying to obtain 792.0g of oxytocin raw material.
Example 3
Taking 1000g of oxytocin crude product, adding 4938.3mL (4000g) of 1-butanol, heating to 35 ℃, adding 19096.1mL (15000g) of isopropanol and 571.4mL (550g) of cyclohexanol, cooling to 7 ℃, standing for 16 hours, filtering, washing a filter cake with isopropanol, then adding 4938.3mL (4000g) of isopropanol to dissolve completely, adding 19096.1mL (15000g) of isopropanol and 571.4mL (550g) of cyclohexanol, cooling to 5 ℃, standing for 24 hours, filtering, washing the filter cake with isopropanol, and freeze-drying to obtain 796.7g of oxytocin raw material.
Example 4
Adding 1-butanol 4321mL (3500g) into 1000g of oxytocin crude product, heating to 35 ℃, adding isopropanol 15276.9mL (12000g) and cyclohexanol 415.6g (400g), cooling to 5 ℃, standing for 14 hours, filtering, washing a filter cake with isopropanol, adding 1-butanol 4321mL (3500g) for complete dissolution, adding isopropanol 15276.9mL (12000g) and cyclohexanol 415.6g (400g), cooling to 0 ℃, standing for 14 hours, filtering, washing the filter cake with isopropanol, and freeze-drying to obtain the oxytocin raw material 782.1 g.
Example 5
Taking 1000g of oxytocin crude product, adding 5555.6mL (4500g) of 1-butanol, heating to 35 ℃, adding 22915.3mL (18000g) of isopropanol and 779.3mL (750g) of cyclohexanol, cooling to 10 ℃, standing for 22 hours, filtering, washing a filter cake with isopropanol, then adding 5555.6mL (4500g) of 1-butanol to dissolve completely, adding 22915.3mL (18000g) and 779.3mL (750g) of cyclohexanol, cooling to 5 ℃, standing for 22 hours, filtering, washing the filter cake with isopropanol, and freeze-drying to obtain 783.4g of oxytocin raw material.
Test examples
Comparative example 1
Taking 100g of oxytocin crude product, adding 100g of deionized water, completely dissolving, adding 1909.6mL (1500g) of isopropanol, standing for 24 hours, filtering, washing a filter cake with isopropanol, and freeze-drying to obtain 707.2g of oxytocin raw material;
comparative example 2
100g of oxytocin crude product is taken, 100g of deionized water is added, the dissolution is complete, 1909.6mL (1500g) of isopropanol and 1558.6mL (1500g) of cyclohexanol are added, the mixture is kept stand for 24 hours, the filtration is carried out, a filter cake is washed by the isopropanol, and the freeze drying is carried out, so that 714.4g of oxytocin raw material is obtained.
Cold-hot cycling test: taking oxytocin raw materials obtained by different preparation methods, after detection and analysis, taking 2g of the raw materials, adding 100mL of water for injection, standing at 1-10 ℃ for 2 days, standing at 25 ℃ for two days for 1 cycle, circulating for three times, freeze-drying, and carrying out detection and analysis on samples, wherein analysis results are shown in table 2.
[ MEASUREMENT OF CONTENT ]
Measuring by high performance liquid chromatography (general rule 0512)
Chromatographic conditions and system applicability test: by using AgilentZorbax SB-C18(250mm multiplied by 4.6mm, 5 mu m) chromatographic column, mobile phase A is 15.6g/L sodium dihydrogen phosphate solution, mobile phase B is 50% acetonitrile, gradient elution is carried out for 0-20min and 30% -50% A, detection wavelength is 220nm, sample injection amount is 25 mu L, and flow rate is 1.0 mL/min.
The determination method comprises the following steps: taking about 25mg of oxytocin reference substance, precisely weighing, adding the mobile phase A to dissolve and dilute to prepare 0.25mg/mL oxytocin solution. Under the condition, the retention time of oxytocin is 14.205min, the separation degree of an oxytocin peak and an adjacent impurity peak is 2.16, and the number of theoretical plates is 2.2855 multiplied by 104. Taking a sample of about 25mg, precisely weighing, placing in a measuring flask of 100mL, dissolving by using a mobile phase A, and carrying out constant volume to prepare a test solution of oxytocin of 0.25 mg/mL; and preparing a control solution of oxytocin at a concentration of 0.25mg/mL by taking an appropriate amount of the oxytocin control. Measuring according to the above chromatographic conditions, recording chromatogram, and calculating according to external standard method.
[ related substances ]
Measuring by high performance liquid chromatography (general rule 0512)
Chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; gradient elution is carried out according to the table 1 by taking 0.1mol/L sodium dihydrogen phosphate solution as a mobile phase A and acetonitrile-water (1: 1) as a mobile phase B; the flow rate was 1.0mL per minute and the detection wavelength was 220 nm. The number of theoretical plates is not less than 2000 calculated according to oxytocin peak.
TABLE 1 gradient of mobile phase
The determination method comprises dissolving the product in 0.lmol/L sodium dihydrogen phosphate solution, diluting to obtain 0.1mg solution per lml, precisely measuring 20 μ L by liquid chromatograph, and recording chromatogram until the retention time of main peak is 2 times. If impurity peaks exist in a chromatogram of a test solution, the peak area of each single impurity is not more than 0.02 times (2.0%) of the total peak area, and the sum of the peak areas of the impurities is not more than 0.05 times (5.0%) of the total peak area.
TABLE 2 comparison of oxytocin quality in different methods
And (4) test conclusion: the data before the test shows that: the oxytocin content obtained by the method is more than 95 percent, the single maximum impurity content is less than 1.0 percent, the total impurity content is less than 2.0 percent, the oxytocin content obtained by the comparative example method is less than 90 percent, the single maximum impurity content is more than 1.0 percent, and the total impurity content is more than 5 percent (the oxytocin quality of the comparative example does not meet the quality standard requirement), thereby fully indicating that the process method is more scientific; after the cold-hot cycle test, oxytocin according to the examples of the present invention was more stable than oxytocin according to the comparative examples.
Example 6
The prescription of the injection comprises: example 3 oxytocin raw material 50mg, L-glutamic acid 1mg, glycine 3.3 mg.
The preparation method comprises the following steps: adding glycine into 800mL of water for injection, stirring uniformly, adding oxytocin raw material, adding L-glutamic acid, adding water for injection to 1000mL, filtering with a 0.22 μm filter element, and filling to obtain 1000 injection.
Example 7
The prescription of the injection comprises: example 3 oxytocin raw material 50mg, L-glutamic acid 1mg, glycine 3.8 mg.
The preparation method comprises the following steps: adding glycine into 800mL of water for injection, stirring uniformly, adding oxytocin raw material, adding L-glutamic acid, adding water for injection to 1000mL, filtering with a 0.22 μm filter element, and filling to obtain 1000 injection.
Example 8
The prescription of the injection comprises: example 3 oxytocin raw material 50mg, L-glutamic acid 1mg, glycine 4.0 mg.
The preparation method comprises the following steps: adding glycine into 800mL of water for injection, stirring uniformly, adding oxytocin raw material, adding L-glutamic acid, adding water for injection to 1000mL, filtering with a 0.22 μm filter element, and filling to obtain 1000 injection.
Example 9
The prescription of the injection comprises: example 3 oxytocin raw material 50mg, L-glutamic acid 1mg, glycine 4.2 mg.
The preparation method comprises the following steps: adding glycine into 800mL of water for injection, stirring uniformly, adding oxytocin raw material, adding L-glutamic acid, adding water for injection to 1000mL, filtering with a 0.22 μm filter element, and filling to obtain 1000 injection.
Example 10
The prescription of the injection comprises: example 3 oxytocin raw material 50mg, L-glutamic acid 1mg, glycine 4.5 mg.
The preparation method comprises the following steps: adding glycine into 800mL of water for injection, stirring uniformly, adding oxytocin raw material, adding L-glutamic acid, adding water for injection to 1000mL, filtering with a 0.22 μm filter element, and filling to obtain 1000 injection.
Comparative example 3: example 3 oxytocin: 50 mg; cysteine hydrochloride 50 mg; the water for injection is added to 1000 ml.
The preparation method comprises the following steps: adding glycine into 800mL of water for injection, stirring uniformly, adding oxytocin raw material, adding L-glutamic acid, adding water for injection to 1000mL, filtering with a 0.22 μm filter element, and filling to obtain 1000 injection.
(1) Light test
The different injections are placed under the condition of the illumination intensity of 4500Lx for illumination stability test, are placed for 10 days, and are randomly sampled and measured on the 0 th day, the 5 th day and the 10 th day respectively. The test results are shown in Table 3.
(2) High temperature test
Taking different injections, respectively placing the injections in a drying oven at 60 ℃ for 10 days, and randomly sampling on the 0 th day, the 5 th day and the 10 th day for determination. The test results are shown in Table 4.
TABLE 3 illumination test results
TABLE 4 high temperature test results
And (4) test conclusion: the tests show that the preparation composition has scientific significance because the oxytocin content, the single maximum impurity and the total impurity content change are small compared with a comparative example when the L-glutamic acid and the glycine in a certain proportion are used as the pharmaceutic adjuvants of the oxytocin.
Claims (1)
1. A preparation method of oxytocin-containing injection is characterized in that the injection comprises the following raw and auxiliary materials: oxytocin raw material, L-glutamic acid and glycine; wherein the weight ratio of oxytocin raw material, L-glutamic acid and glycine is 50: 1: 3.3-4.5;
the preparation method of the injection comprises the following steps:
adding glycine into water for injection, stirring, adding oxytocin raw material, adding L-glutamic acid, adding water for injection, filtering with 0.22 μm filter element, and packaging to obtain injection;
the preparation method of the oxytocin raw material comprises the following steps:
adding 1-butanol into a oxytocin crude product, heating to 30-40 ℃, adding isopropanol and cyclohexanol, cooling to 5-10 ℃, standing for 12-24 hours, filtering, washing a filter cake with isopropanol, adding 1-butanol to dissolve completely, adding isopropanol and cyclohexanol, cooling to 0-5 ℃, standing for 12-24 hours, filtering, washing the filter cake with isopropanol, and freeze-drying to obtain an oxytocin raw material; wherein the weight ratio of the oxytocin crude product to the 1-butanol is 1: 3-5; wherein the weight ratio of the oxytocin crude product to the isopropanol and the cyclohexanol is 1: 10-20: 0.3-0.8.
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| CN113827700B (en) * | 2021-09-30 | 2024-06-04 | 上海上药第一生化药业有限公司 | Pharmaceutical composition containing oxytocin and freeze-dried powder thereof and purification method of oxytocin |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2016055550A1 (en) * | 2014-10-07 | 2016-04-14 | Cyprumed Gmbh | Pharmaceutical formulations for the oral delivery of peptide or protein drugs |
| WO2017018742A1 (en) * | 2015-07-24 | 2017-02-02 | Hanmi Pharm. Co., Ltd. | Method of preparing physiologically active polypeptide conjugate |
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| US7906137B2 (en) * | 2004-05-21 | 2011-03-15 | Mediplex Corporation, Korea | Delivery agents for enhancing mucosal absorption of therapeutic agents |
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| JO3400B1 (en) * | 2010-09-30 | 2019-10-20 | Ferring Bv | Pharmaceutical composition of carbetocin |
| CN102228678A (en) * | 2011-06-22 | 2011-11-02 | 深圳翰宇药业股份有限公司 | Carbetocin pharmaceutical composition and preparation method thereof |
| CN103830720A (en) * | 2014-03-25 | 2014-06-04 | 深圳翰宇药业股份有限公司 | Medicine composition containing oxytocin |
| CN104056249B (en) * | 2014-07-08 | 2016-07-06 | 西藏易明西雅医药科技股份有限公司 | A kind of pharmaceutical composition containing active component carbetocin and preparation thereof |
| CN104650193B (en) * | 2015-01-28 | 2017-12-12 | 南京新百药业有限公司 | A kind of oxytocin recrystallization method |
| CN106831951A (en) * | 2017-01-11 | 2017-06-13 | 蚌埠丰原医药科技发展有限公司 | A kind of purification process of oxytocin |
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| WO2016055550A1 (en) * | 2014-10-07 | 2016-04-14 | Cyprumed Gmbh | Pharmaceutical formulations for the oral delivery of peptide or protein drugs |
| WO2017018742A1 (en) * | 2015-07-24 | 2017-02-02 | Hanmi Pharm. Co., Ltd. | Method of preparing physiologically active polypeptide conjugate |
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Effective date of registration: 20191226 Address after: 100176 Room 405, floor 4, building 2, No. 99, Kechuang 14th Street, Beijing Economic Development Zone, Daxing District, Beijing Applicant after: Beijing Xinli Pharmaceutical Technology Co., Ltd Address before: 101400 Beijing Huairou Quanhe Garden Area II No.3 Applicant before: Beijing Jinyang United Technology Development Co., Ltd. |
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