CN105832664A - Isosorbide dinitrate injection and preparation method thereof - Google Patents
Isosorbide dinitrate injection and preparation method thereof Download PDFInfo
- Publication number
- CN105832664A CN105832664A CN201610405340.1A CN201610405340A CN105832664A CN 105832664 A CN105832664 A CN 105832664A CN 201610405340 A CN201610405340 A CN 201610405340A CN 105832664 A CN105832664 A CN 105832664A
- Authority
- CN
- China
- Prior art keywords
- injection
- isosorbide dinitrate
- preparation
- sodium chloride
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Abstract
The invention provides an isosorbide dinitrate injection, which is prepared from isosorbide dinitrate, sodium chloride, sodium hydrogen sulfite, pH regulators and injection water. The isosorbide dinitrate and the sodium chloride are weighed according to the recipe quantity and are added into a proper amount of injection water; the materials are stirred to be uniformly mixed; the sodium chloride in the recipe quantity is added into the solution; the materials are stirred for dissolution; the pH value is regulated by pH regulators. The injection water is regulated to the constant volume to the total quantity; filtering and filling are performed; 121 DEG C hog pressing steam sterilization is performed for 15min; the materials are discharged from a box; a finished product is obtained after lamp inspection. The injection has the advantages that the yield is high; the safety is high; the quality is stable; the injection is worth of being popularized in the production process .
Description
Technical field
The present invention relates to pharmaceutical technology field, be specifically related to a kind of isosorbide dinitrate injection and preparation method thereof.
Background technology
Heart failure (Heart Failure) is the end stage eventually of various cardiovascular disease.According to clinical symptoms can be divided into the left heart,
The right heart and whole heart failure, wherein most common with left heart failure.It is the heart that acute myocardial infarction merges the basic physiological pathology of acute left heart failure
Myocardial ischemia is persistently and seriously, myocardial contraction substantially reduces and (or) cardiac load is significantly increased, thus causes part cardiac muscle acute
Downright bad, cardiac output drastically declines and pressure of pulmonary circulation steeply rises.Because its M & M remains high, and become
One of great difficult problem that 21 century Vasculocardiology Deparment doctor faces.
Along with the progress of heart failure pathophysiological mechanism, the Drug therapy of heart failure is from using diuretic minimizing water-sodium retention, ocean
Radix Rehmanniae improves abnormal hemodynamics, vasodilation improves the traditional mode of symptom, develops into for neuroendocrine different
Neuroendocrine antagonist ACEI class medicine, beta-blocker and aldosterone receptor antagonist, the controlling of heart failure often activated
Treatment is not only to improve symptom, it is often more important that prevent and delay the development of remodeling ventricle.Said medicine is by domestic unfaithful intention
The treatment guidelines that declines is classified as the standard regimens of heart failure, is widely used in clinic, hence it is evident that reduce heart failure mortality risk.Nitric acid
Ester, as the century-old medicine for the treatment of cardiovascular disease, refers in chemical constitution, route of administration, preparation, clinical application over nearly 30 years
The aspect such as levy and quickly grow and obtain repeatly important breakthrough, day by day show powerful vitality, so merging at older patients with acute heart infarction
The clinical treatment of acute left heart failure gradually attract attention.Isosorbide dinitrate injection belongs to nitrate esters medicine,
Its main mechanism is: 1. can make vascular smooth muscle relaxation, causes PeV vasodilation, thus reduces vein and return
Flow, reduce cardiac preload, alleviate pulmonary venous pleonaemia；2. dilating coronary blood vessel, improves blood supply of cardiac muscle；3. can reduce during heavy dose
Artery resistance, alleviate cardiac afterload, thus increase cardiac output.Merge in acute left heart failure at treatment older patients with acute heart infarction
Obtain good clinical efficacy.
But in actual production, inventor finds, in the pouring process of medicinal liquid, medicinal liquid can produce substantial amounts of bubble, bubble
Hang over and can not eliminate in time on filling pin, thus adhered to bottleneck, if using cillin bottle fill, it may appear that plug jumping is existing
As, if using ampoule bottle fill, the medicinal liquid carbonization of adhesion can be caused during high temperature sealing by fusing, cause visible foreign matters
Underproof situation occurs.
Summary of the invention
For above not enough, the invention provides a kind of isosorbide dinitrate injection, by sorbide nitrate, sodium chloride,
Sodium sulfite, pH adjusting agent and water for injection composition.
Described isosorbide dinitrate injection, Isosorbide ester concentration is 0.8～1.2mg/ml, preferably 1.0mg/ml.
Described isosorbide dinitrate injection, concentration of sodium bisulphite is 0.2～0.4mg/ml, preferably 0.3mg/ml.
Described isosorbide dinitrate injection, pH adjusting agent is in hydrochloric acid, acetic acid, phosphoric acid, citric acid, benzenesulfonic acid
One or more, preferably hydrochloric acid.
The preparation method of a kind of described isosorbide dinitrate injection, comprises the following steps:
The sorbide nitrate and the sodium sulfite that weigh recipe quantity join in appropriate water for injection, are uniformly mixed,
The sodium chloride weighing recipe quantity joins in above-mentioned solution, and stirring and dissolving regulates pH value by pH adjusting agent, uses water for injection
It is settled to total amount；Filtering, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet, lamp inspection gets product.
The preparation method of described isosorbide dinitrate injection, pH regulator scope is 5.8～6.6, preferably 6.2.
The isosorbide dinitrate injection that the present invention provides: sodium chloride is isoosmotic adjusting agent, its be incorporated as making described injection in
Isosmotic solution.
Isosorbide dinitrate injection of the present invention has the advantage that
Foamless generation in preparation process, it is to avoid owing to the appearance of foam causes visible foreign matters and the generation of plug jumping situation,
Improve the safety of product and the yield of product, invention formulation steady quality simultaneously, indices all meets the requirements.
Detailed description of the invention
Following example further describe preparation process and the beneficial effect of the present invention, and embodiment is only used for the purpose of illustration, no
Limiting the scope of the present invention, those of ordinary skill in the art are obviously changed according to what the present invention made and modify also simultaneously
Comprise within the scope of the present invention.
Embodiment 1
1) prescription
| Sorbide nitrate | 2.4g |
| Sodium chloride | 2.67g |
| Sodium sulfite | 0.6g |
| Water for injection | Add to 3000ml |
2) preparation method:
The sorbide nitrate and the sodium sulfite that weigh recipe quantity join in appropriate water for injection, are uniformly mixed,
The sodium chloride weighing recipe quantity joins in above-mentioned solution, stirring and dissolving, regulates pH to 5.8 with 0.1mol/L dilute hydrochloric acid solution,
PH regulator is complete, is settled to total amount with water for injection；Filter, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet,
Lamp inspection gets product.
Embodiment 2
1) prescription
| Sorbide nitrate | 3.6g |
| Sodium chloride | 2.55g |
| Sodium sulfite | 1.2g |
| Water for injection | Add to 3000ml |
2) preparation method:
The sorbide nitrate and the sodium sulfite that weigh recipe quantity join in appropriate water for injection, are uniformly mixed,
The sodium chloride weighing recipe quantity joins in above-mentioned solution, stirring and dissolving, regulates pH to 6.6 with 0.1mol/L citric acid soln,
PH regulator is complete, is settled to total amount with water for injection；Filter, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet,
Lamp inspection gets product.
Embodiment 3
1) prescription
| Sorbide nitrate | 3.0g |
| Sodium chloride | 2.625g |
| Sodium sulfite | 0.9g |
| Water for injection | Add to 3000ml |
2) preparation method:
The sorbide nitrate and the sodium sulfite that weigh recipe quantity join in appropriate water for injection, are uniformly mixed,
The sodium chloride weighing recipe quantity joins in above-mentioned solution, stirring and dissolving, regulates pH to 6.2 with 0.1mol/L dilute hydrochloric acid solution,
PH regulator is complete, is settled to total amount with water for injection；Filter, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet,
Lamp inspection gets product.
Comparative example 1
1) prescription
| Sorbide nitrate | 3.0g |
| Sodium chloride | 2.7g |
| Water for injection | Add to 3000ml |
2) preparation method:
The sorbide nitrate and the sodium chloride that weigh recipe quantity join in appropriate water for injection, are uniformly mixed, and use
0.1mol/L dilute hydrochloric acid solution regulation pH to 6.2, pH regulator is complete, is settled to total amount with water for injection；Filter, fill,
121 DEG C of hot pressing steam sterilizing 15min, outlet, lamp inspection gets product.
Comparative example 2
1) prescription
| Sorbide nitrate | 3.0g |
| Sodium chloride | 2.7g |
| L-cysteine hydrochloride | 1.8g |
| Water for injection | Add to 3000ml |
Remarks: pH adjusting agent is the mixture (the two mol ratio is 7:1) of sorbic acid and 0.1mol/L ascorbic acid
2) preparation method:
The sodium chloride weighing recipe quantity joins appropriate water for injection, stirring and dissolving, adds the sorbide nitrate of recipe quantity
And L-cysteine hydrochloride, stirring to solution is colourless clear liquid, measures pH value, resists with sorbic acid and 0.1mol/L
Mixture (the two mol ratio is 7:1) the regulation pH to 6.0 of bad hematic acid, pH regulator is complete, is settled to total amount, sampling inspection
Surveying intermediate products solution, filter, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet, lamp inspection gets product.
Comparative example 3
1) prescription
| Sorbide nitrate | 3.0g |
| Sodium chloride | 2.625g |
| Sodium sulfite | 0.9g |
| Water for injection | Add to 3000ml |
2) preparation method:
The sorbide nitrate and the sodium sulfite that weigh recipe quantity join in appropriate water for injection, are uniformly mixed,
The sodium chloride weighing recipe quantity joins in above-mentioned solution, stirring and dissolving, regulates pH to 5.0 with 0.1mol/L dilute hydrochloric acid solution,
PH regulator is complete, is settled to total amount with water for injection；Filter, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet,
Lamp inspection gets product.
Comparative example 4
1) prescription
2) preparation method:
The sorbide nitrate and the sodium sulfite that weigh recipe quantity join in appropriate water for injection, are uniformly mixed,
The sodium chloride weighing recipe quantity joins in above-mentioned solution, stirring and dissolving, regulates pH to 6.2 with 0.1mol/L dilute hydrochloric acid solution,
PH regulator is complete, is settled to total amount with water for injection；Filter, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet,
Lamp inspection gets product.
Comparative example 5
1) prescription
| Sorbide nitrate | 3.0g |
| Sodium chloride | 2.625g |
| Sodium sulfite | 1.5g |
| Water for injection | Add to 3000ml |
2) preparation method:
The sorbide nitrate and the sodium sulfite that weigh recipe quantity join in appropriate water for injection, are uniformly mixed,
The sodium chloride weighing recipe quantity joins in above-mentioned solution, stirring and dissolving, regulates pH to 6.2 with 0.1mol/L dilute hydrochloric acid solution,
PH regulator is complete, is settled to total amount with water for injection；Filter, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet,
Lamp inspection gets product.
Checking embodiment
(1) product yield contrast
The preparation finished product yield implemented embodiment 1～3 and contrast obtained by 1～5 examples collects, and it the results are shown in Table 1.
Table 1 embodiment 1～3 and the contrast of comparative example 1～5 finished product yield
From experiment investigation result: preparation yield comparative example to be substantially better than that embodiment 1～3 prepares 1～2 and right
Ratio embodiment 4, and in prescription, add the sodium sulfite of excess and its pH value is regulated in addition to the present invention to its yield also
Not impact.
(2) long term test
Preparation obtained by embodiment 1～3 and contrast enforcement 3,5 is put into 25 DEG C, in RH60% climatic chamber, respectively
In 0,6, December sampling, investigate its appearance character, it is seen that foreign body, pH, have the situation of change of related substance and content, knot
Fruit is shown in Table 2.
Table 2 long term test investigates result
From experiment investigation result: preparation indices obtained by the embodiment of the present invention 1～3 all meets regulation, and contrasts reality
Execute preparation obtained by example 3,5 along with standing time prolongation its have related substance to become big, its content reduces, and considers, this
Bright yield is high, and safety is good, steady quality, is worth promoting aborning.
Claims (10)
1. an isosorbide dinitrate injection, it is characterised in that by sorbide nitrate, sodium chloride, sodium sulfite, pH
Regulator and water for injection composition.
Isosorbide dinitrate injection the most according to claim 1, it is characterised in that Isosorbide ester concentration is
0.8～1.2mg/ml.
Isosorbide dinitrate injection the most according to claim 1, it is characterised in that Isosorbide ester concentration is
1.0mg/ml。
Isosorbide dinitrate injection the most according to claim 1, it is characterised in that concentration of sodium bisulphite is
0.2～0.4mg/ml.
Isosorbide dinitrate injection the most according to claim 1, it is characterised in that concentration of sodium bisulphite is 0.3mg/ml.
Isosorbide dinitrate injection the most according to claim 1, it is characterised in that pH adjusting agent selected from hydrochloric acid, acetic acid,
One or more in phosphoric acid, citric acid, benzenesulfonic acid.
Isosorbide dinitrate injection the most according to claim 1, it is characterised in that pH adjusting agent is hydrochloric acid.
8. the preparation method of an isosorbide dinitrate injection as claimed in claim 1, it is characterised in that comprise the following steps:
The sorbide nitrate and the sodium sulfite that weigh recipe quantity join in appropriate water for injection, are uniformly mixed,
The sodium chloride weighing recipe quantity joins in above-mentioned solution, and stirring and dissolving regulates pH by pH adjusting agent, fixed with water for injection
Hold to total amount；Filtering, fill, 121 DEG C of hot pressing steam sterilizing 15min, outlet, lamp inspection gets product.
The preparation method of isosorbide dinitrate injection the most according to claim 8, it is characterised in that pH regulator scope is
5.8～6.6.
The preparation method of isosorbide dinitrate injection the most according to claim 8, it is characterised in that pH regulator scope is
6.2。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610405340.1A CN105832664A (en) | 2016-06-10 | 2016-06-10 | Isosorbide dinitrate injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610405340.1A CN105832664A (en) | 2016-06-10 | 2016-06-10 | Isosorbide dinitrate injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105832664A true CN105832664A (en) | 2016-08-10 |
Family
ID=56575629
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610405340.1A Pending CN105832664A (en) | 2016-06-10 | 2016-06-10 | Isosorbide dinitrate injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105832664A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115073486A (en) * | 2022-06-29 | 2022-09-20 | 回音必集团抚州制药有限公司 | Isosorbide dinitrate and preparation method of injection thereof |
| CN116251057A (en) * | 2022-12-29 | 2023-06-13 | 平光制药股份有限公司 | Isosorbide dinitrate injection and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1663569A (en) * | 2004-03-06 | 2005-09-07 | 杨喜鸿 | Fructose injection for cardiovascular medicine |
| CN104027329A (en) * | 2014-06-04 | 2014-09-10 | 回音必集团(江西)东亚制药有限公司 | Isosorbide dinitrate sodium chloride injection |
| CN105311040A (en) * | 2015-11-09 | 2016-02-10 | 邓学峰 | Fructose diphosphate containing novel pharmaceutical composition injection for treating circulation system diseases |
| CN105476955A (en) * | 2016-01-06 | 2016-04-13 | 山东新时代药业有限公司 | Isosorbide dinitrate injection and preparation method thereof |
-
2016
- 2016-06-10 CN CN201610405340.1A patent/CN105832664A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1663569A (en) * | 2004-03-06 | 2005-09-07 | 杨喜鸿 | Fructose injection for cardiovascular medicine |
| CN104027329A (en) * | 2014-06-04 | 2014-09-10 | 回音必集团(江西)东亚制药有限公司 | Isosorbide dinitrate sodium chloride injection |
| CN105311040A (en) * | 2015-11-09 | 2016-02-10 | 邓学峰 | Fructose diphosphate containing novel pharmaceutical composition injection for treating circulation system diseases |
| CN105476955A (en) * | 2016-01-06 | 2016-04-13 | 山东新时代药业有限公司 | Isosorbide dinitrate injection and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115073486A (en) * | 2022-06-29 | 2022-09-20 | 回音必集团抚州制药有限公司 | Isosorbide dinitrate and preparation method of injection thereof |
| CN115073486B (en) * | 2022-06-29 | 2024-02-20 | 江西东抚制药有限公司 | Isosorbide dinitrate and preparation method of injection thereof |
| CN116251057A (en) * | 2022-12-29 | 2023-06-13 | 平光制药股份有限公司 | Isosorbide dinitrate injection and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Grollman et al. | The renal excretion of citrate | |
| BR112013000744A2 (en) | use of a thromboxane a2 receptor antagonist for the prevention or treatment of hepatorrenal syndrome, hepatic encephalopathy, and associated diseases | |
| CN105476955B (en) | A kind of isosorbide dinitrate injection and preparation method thereof | |
| CN105832664A (en) | Isosorbide dinitrate injection and preparation method thereof | |
| CN102579329B (en) | Milrinone lactate injection and preparation method thereof | |
| CN101032512B (en) | Medicine composition for expanding blood volume and the preparing method thereof | |
| CN103304500A (en) | Novel anti-diabetic compound, as well as preparation method and application thereof | |
| CN101007003A (en) | A stable torasemide injection and its preparation method | |
| Downing et al. | Myocardial and coronary vascular responses to insulin in the diabetic lamb | |
| Darrow | Therapeutic measures promoting recovery from the physiologic disturbances of infantile diarrhea | |
| CN103304501A (en) | Anti-diabetic compound, as well as preparation method and application thereof | |
| CN102266343A (en) | Fasudil hydrochloride pharmaceutical composition for injection | |
| CN104706655B (en) | Meglumine cyclic adenosine for injecta powder-injection pharmaceutical composition and preparation method | |
| CN106309481A (en) | Compound potassium aspartate-glucose injection and preparation method thereof | |
| RU2327228C1 (en) | Method of rat's cardiovasorenal arterial hypertension modelling | |
| CN105963247A (en) | Preparation method of injection medicine for improving stability of quercetin medicine injection preparation | |
| CN102526098A (en) | New application of compound sodium chloride potassium chloride injection | |
| CN104922661B (en) | A kind of pharmaceutical composition and preparation method thereof containing serelaxin | |
| CN109528633A (en) | Inosine injection and preparation method thereof | |
| CN105287370B (en) | A kind of preparation method of inosine and combinations thereof composition injection | |
| CN106074366B (en) | The injection and preparation method thereof for treating the disturbance of consciousness after brain trauma and brain surgery | |
| CN102274194B (en) | Pharmaceutical composition containing tropisetron compound and preparation method thereof | |
| CN102949413B (en) | Method for preparing invert sugar and electrolytes injection | |
| CN104490903B (en) | A kind of Compound vitamine injection pharmaceutical composition and preparation method thereof | |
| RU2430428C1 (en) | Method of correcting hyperhomocysteine-induced endothelial dysfunction by medication "phosphogliv" capsules |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160810 |
|
| RJ01 | Rejection of invention patent application after publication |