CN104922060A - Sodium ibandronate injection composition - Google Patents
Sodium ibandronate injection composition Download PDFInfo
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- CN104922060A CN104922060A CN201510266697.1A CN201510266697A CN104922060A CN 104922060 A CN104922060 A CN 104922060A CN 201510266697 A CN201510266697 A CN 201510266697A CN 104922060 A CN104922060 A CN 104922060A
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- ibandronate
- glucose
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Abstract
The invention provides a sodium ibandronate injection composition. A sodium ibandronate injection comprises sodium ibandronate serving as an active ingredient, glucose serving as a stabilizer and water for injection. The sodium ibandronate injection has the characteristics of simple prescription, high stability, high safety, suitability for industrial production and the like.
Description
Technical field
The present invention relates to technical field of medicine, be specifically related to a kind of Ibandronate composition and method of making the same.
Background technology
Venous transfusion is the main path of clinical treatment and first aid using medicine and supply nutrition, and medication infusion phlebitis is one of common clinically drug-induced disease.Generally believe at present, phlebitis forms one of venothrombotic risk factor.The pH value of blood of human body is 7.35-7.45, and the pH scope that human body can tolerate transfusion is 4-9.Transfusion pH lower than 4 or higher than 9 time, can cause pain and phlebitic generation, and the phlebitic order of severity is directly related with the pH of transfusion, pH value is lower, and phlebitis is more serious.Japan Otsuka Pharmaceutical Co., Ltd. Kuwahara etc. adopts rabbit to test, result show instillation pH value lower than 4.5 transfusion cause phlebitic incidence rate up to 100%, along with the continuous rising of transfusion pH value, the degree of phlebitic incidence rate and inflammation constantly declines, pH rise to 6.5 and more than, substantially there is not phlebitis.(Chinese medical forward position, 2009,4 (22): 13)
Ibandronate (Sodium Ibandronate) belongs to the bisphosphonate compound of the third generation, be applicable to or without the hypercalcemia that the malignant tumor of Bone tumour causes, be used for the treatment of the diseases such as the osteodynia that malignant osteolytic Bone tumour causes.Ibandronate is unstable in aqueous, easily degrades, and main catabolite is free phosphorus hydrochlorate.
Prior art has some to study in the related substance controlling Ibandronate and stability, but still there are some problems.Such as, commercialized product
and comprise in the prescription of CN103239396 there is corrosive acetate; CN103961313 adopts citrate to increase stability, but citric acid has anticoagulant active, is not suitable as the adjuvant of injection; CN103385882 then have employed there is severe compromise sodium pyrosulfite as antioxidant; CN103070824 adopts phosphate buffer to replace acetate buffer, but its related substances is still higher.
Therefore, all there is the problems such as adjuvant safety is low, its related substances is high in Ibandronate of the prior art.How both to adopt the pharmaceutic adjuvant that safety is higher, and effectively can control again the related substance of Ibandronate, fundamentally ensure drug safety, and remained and need those skilled in the art to put forth effort the technical problem solved.
Summary of the invention
In field of pharmaceutical preparations, particularly in medicinal liquid injection field, no matter be as the prescription constituent with injection, or use with medicinal liquid injection compatibility, glucose is all obtain using for a long time, widely as osmotic pressure regulator usually, has high safety.
In the R&D process of Ibandronate, we are surprised to find that, utilize conventional pharmaceutical adjuvants---the glucose that this safety is high, its related substances of Ibandronate can be controlled to extremely low level.The adjuvant of safety, simple prescription, low production cost, makes the present invention very be applicable to suitability for industrialized production.
Based on above-mentioned discovery, we complete the present invention.Particularly, the invention provides a kind of Ibandronate, the content of stabilizing agent is 3-10% (w/v), and it is composed as follows:
Ibandronate (in ibandronic acid) 1g,
Stabilizing agent 30-100g,
Water for injection adds to 1L,
Wherein, described stabilizing agent is selected from glucose, sorbitol, mannitol or its mixture.
Invention especially provides following Ibandronate:
1) Ibandronate, it is composed as follows:
Ibandronate (in ibandronic acid) 1g,
Glucose 30g,
Water for injection adds to 1L.
2) Ibandronate, it is composed as follows:
Ibandronate (in ibandronic acid) 1g,
Glucose 50g,
Water for injection adds to 1L.
3) Ibandronate, it is composed as follows:
Ibandronate (in ibandronic acid) 1g,
Glucose 100g,
Water for injection adds to 1L.
As the preferred technical solution of the present invention, wherein said stabilizing agent is glucose and sorbitol, the preferred 4-8% of content (w/v) of stabilizing agent, and the weight ratio of glucose and sorbitol is 2-3:1.More specifically, following technical scheme is related to:
1) Ibandronate, it is composed as follows:
2) Ibandronate, it is composed as follows:
3) Ibandronate, it is composed as follows:
As another optimal technical scheme of the present invention, wherein said Ibandronate also comprises pH adjusting agent, such as hydrochloric acid, sodium hydroxide.
For aforementioned Ibandronate of the present invention, present invention also offers following preparation method: ibandronate, glucose add 80% water for injection and dissolve, and add needle-use activated carbon 0.05%, stirring and adsorbing 30 minutes, filter decarburization, with 0.22 μm of filter membrane fine straining, inject water to full volumetric, pH should be 4.0-6.0, can regulate by pH adjusting agent if desired, subpackage, 1-6ml/ props up, 121 DEG C of sterilizings 15 minutes, obtain Ibandronate.
The using dosage of the described Ibandronate that the present invention relates to can be determined according to the judgement of clinician.
The present invention is that Ibandronate prescription is simple, effective, particularly utilize this safe drugs adjuvant of glucose, the present invention achieves unforeseeable technique effect: Ibandronate related substance of the present invention can control in very low level.Particularly, when glucose and sorbitol use using the part by weight of 2-3:1 as stabilizing agent, the stability of Ibandronate of the present invention is higher.In addition, the prescription of Ibandronate of the present invention is very simple, safety is high, with low cost, is applicable to suitability for industrialized production.Therefore, compared with prior art, the present invention achieves outstanding substantive distinguishing features and significant technological progress.
Detailed description of the invention
Detailed description of the invention is only and further explains and describes the present invention, should not be interpreted as any limitation of the invention.
In embodiment, supplementary material used is commercial.
Embodiment 1 Ibandronate of the present invention
Prescription:
Ibandronate (in ibandronic acid) 1g,
Glucose 30g,
Water for injection adds to 1L.
Preparation method:
Ibandronate, glucose add 80% water for injection and dissolve, add needle-use activated carbon 0.05%, stirring and adsorbing 30 minutes, filter decarburization, with 0.22 μm of filter membrane fine straining, inject water to full volumetric, pH should be 4.0-6.0, can regulate if desired by pH adjusting agent, subpackage, 1-6ml/ props up, and 121 DEG C of sterilizings 15 minutes, to obtain final product.
Embodiment 2 Ibandronate of the present invention
Prescription:
Ibandronate (in ibandronic acid) 1g,
Glucose 50g,
Water for injection adds to 1L.
Preparation method: with embodiment 1.
Embodiment 3 Ibandronate of the present invention
Prescription:
Ibandronate (in ibandronic acid) 1g,
Glucose 100g,
Water for injection adds to 1L
Preparation method: with embodiment 1.
Embodiment 4 Ibandronate of the present invention
Prescription:
Preparation method: with embodiment 1.
Embodiment 5 Ibandronate of the present invention
Prescription:
Preparation method: with embodiment 1.
Embodiment 6 Ibandronate of the present invention
Prescription:
Preparation method: with embodiment 1.
Reference examples 1 ibandronate sodium chloride injection (CN103070824B embodiment 1)
Prescription (CN103070824B description 0040-0041 section):
Preparation method (CN103070824B description 0042-0052 section):
(1) get recipe quantity 90% water for injection, add recipe quantity sodium chloride successively, disodium hydrogen phosphate dodecahydrate, be stirred to dissolve, without the need to heating.
(2) in above-mentioned gained solution, add recipe quantity sodium Ibandronate monohydrate, stir, make dissolving, without the need to heating.
(3) measure above-mentioned gained and dissolve pH value, with 0.1M hydrochloric acid or sodium hydrate regulator solution pH value to 3.5-4.5.Be settled to total amount with water for injection, stir.
(4) in solution described above, add 0.1% needle-use activated carbon, stir 30min.
(5) above-mentioned gained solution is filtered with 5um titanium filter, removing active carbon.
(6) filtered with 0.2 flat-panel filter by above-mentioned solution, removing is less than other particulate matters of 5um, increases solution clarity further.
(7) above-mentioned gained solution ph is measured, with 0.1M hydrochloric acid or sodium hydrate regulator solution pH value extremely about 3.5-4.5, to correct contingent pH value change in aforementioned two steps.
(8) the above-mentioned gained solution of bottle fill is cutd open, 1ml/ bottle with the colourless low Pyrex peace of 1ml.
(9) by above-mentioned gained injection pressure sterilizing, temperature 121 DEG C, time 15min.
(10) lamp inspection, to obtain final product.
The quality of experimental example Ibandronate and stability study
Ibandronate prepared by Example 1-6 and reference examples 1, detect related index, and carry out influence factor's test, after sterilization, high-temperature storage 10 days, illumination measure related substance % in 10 days respectively, determination of related substances chromatographic condition: be that filler is (as BDS HYPERSIL C18 with octadecylsilane chemically bonded silica, 4.6 × 250mm or polarity close), with the potassium dihydrogen phosphate of 0.02mo/L (every l000ml is containing the disodiumedetate of l00mg) ,-acetonitrile (97:3) is for mobile phase, and determined wavelength is 195nm.Result is as follows:
The Ibandronate obtain embodiment 1-6 and reference examples 1 and commercialized product carry out Journal of Sex Research steady in a long-term (room temperature), and related substance % testing result is as follows:
Claims (10)
1. an Ibandronate, it is composed as follows:
Ibandronate (in ibandronic acid) 1g,
Stabilizing agent 30-100g,
Water for injection adds to 1L,
Wherein, described stabilizing agent is selected from glucose, sorbitol, mannitol or its mixture.
2. Ibandronate according to claim 1, it is composed as follows:
Ibandronate (in ibandronic acid) 1g,
Glucose 30g,
Water for injection adds to 1L.
3. Ibandronate according to claim 1, it is composed as follows:
Ibandronate (in ibandronic acid) 1g,
Glucose 50g,
Water for injection adds to 1L.
4. Ibandronate according to claim 1, it is composed as follows:
Ibandronate (in ibandronic acid) 1g,
Glucose 100g,
Water for injection adds to 1L.
5. Ibandronate according to claim 1, wherein the content of stabilizing agent is 4-8% (w/v).
6. Ibandronate according to claim 1, wherein stabilizing agent is glucose and sorbitol, and the weight ratio of glucose and sorbitol is 2-3:1.
7. Ibandronate according to claim 6, it is composed as follows:
8. Ibandronate according to claim 6, it is composed as follows:
9. Ibandronate according to claim 6, it is composed as follows:
10., according to the arbitrary described Ibandronate of claim 1-9, also comprise pH adjusting agent.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510266697.1A CN104922060B (en) | 2015-05-23 | 2015-05-23 | A kind of Ibandronate composition |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510266697.1A CN104922060B (en) | 2015-05-23 | 2015-05-23 | A kind of Ibandronate composition |
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| CN104922060A true CN104922060A (en) | 2015-09-23 |
| CN104922060B CN104922060B (en) | 2017-10-20 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106389310A (en) * | 2016-08-31 | 2017-02-15 | 安徽省润生医药股份有限公司 | Sodium ibandronate and glucose injection |
| CN106511356A (en) * | 2016-11-01 | 2017-03-22 | 南京恒生制药有限公司 | Sodium ibandronate composition and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101919814A (en) * | 2010-08-02 | 2010-12-22 | 无锡万全医药技术有限公司 | Stable Olprinone HCl injection |
| WO2012093979A1 (en) * | 2011-01-06 | 2012-07-12 | Mahmut Bilgic | Water-soluble dosage forms comprising ibandronate |
| CN103961313A (en) * | 2014-05-30 | 2014-08-06 | 成都苑东药业有限公司 | Ibandronate sodium injection medicine composition and preparation method thereof |
-
2015
- 2015-05-23 CN CN201510266697.1A patent/CN104922060B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101919814A (en) * | 2010-08-02 | 2010-12-22 | 无锡万全医药技术有限公司 | Stable Olprinone HCl injection |
| WO2012093979A1 (en) * | 2011-01-06 | 2012-07-12 | Mahmut Bilgic | Water-soluble dosage forms comprising ibandronate |
| CN103961313A (en) * | 2014-05-30 | 2014-08-06 | 成都苑东药业有限公司 | Ibandronate sodium injection medicine composition and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 徐荣周等 主编: "《药物制剂生产工艺》", 30 April 2008 * |
| 沈阳药学院学报编辑组: "《药剂学专题选编》", 30 September 1977 * |
| 顾学裘 主编: "《药物制剂注解》", 31 May 1983 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106389310A (en) * | 2016-08-31 | 2017-02-15 | 安徽省润生医药股份有限公司 | Sodium ibandronate and glucose injection |
| CN106511356A (en) * | 2016-11-01 | 2017-03-22 | 南京恒生制药有限公司 | Sodium ibandronate composition and preparation method thereof |
| CN106511356B (en) * | 2016-11-01 | 2019-02-26 | 南京恒生制药有限公司 | A kind of ibandronic acid composition of sodium and preparation method thereof |
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| Publication number | Publication date |
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| CN104922060B (en) | 2017-10-20 |
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Address after: 051500 Haixing Road, Zhaoxian County Industrial Park, Shijiazhuang, Hebei Patentee after: HEBEI RENHE YIKANG PHARMACEUTICAL CO., LTD. Address before: 053411 Hengshui City, Hebei, Wuyi County, Qing Liang store town Patentee before: HEBEI RENHE YIKANG PHARMACEUTICAL CO., LTD. |