CN101062011A - Calcium dobesilate injection - Google Patents
Calcium dobesilate injection Download PDFInfo
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- CN101062011A CN101062011A CN 200610046483 CN200610046483A CN101062011A CN 101062011 A CN101062011 A CN 101062011A CN 200610046483 CN200610046483 CN 200610046483 CN 200610046483 A CN200610046483 A CN 200610046483A CN 101062011 A CN101062011 A CN 101062011A
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- injection
- powder needle
- calcium dobesilate
- needle injection
- calcium
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Abstract
The invention discloses an injection and powder needle injection for eyeball rear injection of benzyl sulfonic acid calcium, which is characterized by the following: allocating 0. 2-20/mL benzyl sulfonic acid calcium and 0-50% medicinal findings; setting the medicinal findings as bone holding agent and antioxidant; choosing the bone holding agent from one of manna sugar, vitamin C, carbamide, antacidin, dextran, polyvinylpyrrolidone and aminoacetic acid or their mixture; choosing the antioxidant from one of vitamin C, vitamin E, sodium sulfite, sodium acid sulfite, sodium metabisulfite, natrium hyposulfidum, methilanin, thiourea, editic acid disodium and citric acid or their mixture. This powder needle injection is one of spraying or hot air dry injection, powder needle injection and freezing dry powder needle injection.
Description
Technical field
The present invention relates to contain the pharmaceutical composition of calcium dobesilate.More particularly, be to be the injection and the powder needle injection of feedstock production with the calcium dobesilate, the invention still further relates to this injection and be used for retrobulbar injection.
Background technology
Calcium dobesilate (Calcium Dobesilate) is the novel vascular protective agent, plays main pharmacological to be: reduce its permeability, build up one's resistance to disease; Improve lymph fluid and reflux, reduce edema; Reduce the blood plasma viscosity, correct albumins/globulins ratio, reduce hematoblastic high aggregation, thus the thrombosis of preventing, and improve erythrocytic pliability.This product also can suppress the high penetration effect that vaso-active substance (histamine, 5--hydroxytryptamine, Kallidin I, hyaluronidase, prostaglandin) causes blood capillary, reduces the tunica intima damage, improves the biosynthesis of basement membrane collagen.
The multiple disease that prevention and treatment are caused by blood capillary circulatory disturbance: the retinopathy that diabetes cause; The heart that microcirculation disturbance causes, brain, kidney disease are as myocardial infarction, angina pectoris, thrombus sequela, atherosclerosis of renal glomerulus etc.; Blood viscosity lowering; The prevention microthrombusis; Numb limbs and tense tendons, ice-cold, the pain of trick, diseases such as skin pruritus; Varicosis syndrome etc.
Calcium dobesilate is a water-soluble substances, has only capsule and tablet clinically.Because calcium dobesilate is a benzene ring structure, and phenolic hydroxyl group is arranged on the phenyl ring, instability, chance light is perishable, and hygroscopicity is arranged.Effects such as oxidation, polymerization take place easily at solution state, thereby reduce preparation stability and quality.
Summary of the invention
1. the purpose of this invention is to provide calcium dobesilate injection and powder needle injection, guarantee its safety, stable, effective, be used for retrobulbar injection.Remedied the in great shortage difficult problem of retinopathy medicine that state's internal therapy diabetes cause simultaneously.
2. purpose of the present invention is achieved by following technical proposals:
Prepared calcium dobesilate injection and powder needle injection, this injection and powder needle injection contain calcium dobesilate and pharmaceutic adjuvant.
Wherein, containing calcium dobesilate is 0.2～20mg/mL (annotate: injectable powder is the concentration after dissolving), and pharmaceutic adjuvant accounts for 0～50%.Wherein, described adjuvant comprises skeleton proppant, antioxidant (stabilizing agent).The skeleton proppant is a kind of in mannitol, vitamin C, carbamide, glucose, dextran, polyvidon or the glycine, or their mixture.Antioxidant is vitamin C, vitamin E, sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, methionine (methionine), thiourea, Calcium Disodium Versenate (EDTA-Na
2), citric acid.Described powder needle injection is said spraying or heated drying powder needle injection, freeze drying injection and a powder needle injection dosage form on any pharmaceutics.
By instantiation given below, can further be well understood to the present invention.But they are not limitation of the invention.
Example 1
Take by weighing the 5g calcium dobesilate, 5g mannitol, the 0.5g vitamin C adds water for injection 100mL, makes dissolving, and regulating pH value is 5.5,0.45 μ m filtering with microporous membranes; Filtrate lucifuge under 0 ℃ of condition was placed 6 hours, and 0.1 μ m filtering with microporous membrane is diluted to 500mL with water for injection, fill (2mL/ bottle), or lyophilization, and radiation sterilization, packing gets final product.
Example 2
Take by weighing the 5g calcium dobesilate, 5g mannitol, the 0.5g vitamin E adds water for injection 100mL, makes dissolving, and regulating pH value is 5.5,0.45 μ g filtering with microporous membranes; Filtrate was placed 10 hours down at 1 ℃, and 0.1 μ m filtering with microporous membrane is diluted to 500mL with water for injection, spray drying, and embedding (5mg/ bottle), radiation sterilization, packing gets final product.
Example 3
Take by weighing the 5g calcium dobesilate, 5g mannitol, the 0.5g sodium sulfite adds water for injection 100mL, makes dissolving, and regulating pH value is 5.5,0.45 μ m filtering with microporous membranes; Filtrate was placed 12 hours down at 2 ℃, and 0.1 μ m filtering with microporous membrane is diluted to 500mL with water for injection, spray drying, and embedding (5mg/ bottle), radiation sterilization, packing gets final product.
Example 4
Take by weighing the 5g calcium dobesilate, 2g carbamide, the 0.5g sodium sulfite adds water for injection 100mL, makes dissolving, and regulating pH value is 5.5,0.45 μ m filtering with microporous membranes; Filtrate was placed 15 hours down at 3 ℃, and 0.1 μ m filtering with microporous membrane is diluted to 500ml with water for injection, embedding (2mL/ bottle), and lyophilization, radiation sterilization, packing gets final product.
Example 5
One takes by weighing the 5g calcium dobesilate, the 5g glucose, and the 0.5g sodium pyrosulfite adds water for injection 100mL, makes dissolving, and regulating pH value is 6.0,0.45 μ m filtering with microporous membranes; Filtrate was placed 24 hours down at 3 ℃, was diluted to 500mL with water for injection, 0.1 μ m filtering with microporous membrane, and embedding (2mL/ bottle), lyophilization, radiation sterilization, packing gets final product.
Example 6
Take by weighing the 5g calcium dobesilate, 2g mannitol, 0.5g sodium thiosulfate adds water for injection 100mL, makes dissolving, and regulating pH value is 6.5,0.45 μ m filtering with microporous membranes; Filtrate was placed 36 hours down at 4 ℃, was diluted to 500mL with water for injection, 0.1 μ m filtering with microporous membrane, and embedding (2mL/ bottle), lyophilization, radiation sterilization, packing gets final product.
Example 7
Take by weighing the 5g calcium dobesilate, the 5g dextran, the 0.5g methionine adds water for injection 100ml, makes dissolving, and regulating pH value is 6.5,0.45 μ m filtering with microporous membranes; Filtrate was placed 40 hours down at 4.5 ℃, was diluted to 500mL with water for injection, 0.1 μ m filtering with microporous membrane, and embedding (2mL/ bottle), lyophilization, radiation sterilization, packing gets final product.
Example 8
Take by weighing the 5g calcium dobesilate, each 2g of glucose and mannitol, the 0.5g thiourea adds water for injection 100mL, makes dissolving, and regulating pH value is 7.0,0.45 μ m filtering with microporous membranes; Filtrate was placed 44 hours down at 5 ℃, was diluted to 500mL with water for injection, 0.1 μ m filtering with microporous membrane, and embedding (2mL/ bottle), lyophilization, radiation sterilization, packing gets final product.
Example 9
Take by weighing the 5g calcium dobesilate, 2g polyvidon, 0.5g Calcium Disodium Versenate add water for injection 100mL makes dissolving, and regulating pH value is that 7.5,0.45 μ m filtering with microporous membranes filter; Filtrate was placed 48 hours down at 5 ℃, was diluted to 500mL with water for injection, 0.1 μ m filtering with microporous membrane, and embedding (2mL/ bottle), lyophilization, radiation sterilization, packing gets final product.
Example 10
Take by weighing the 5g calcium dobesilate, the 3g glycine, the 0.5g citric acid adds water for injection 100mL, makes dissolving, and regulating pH value is 7.5,0.45 μ m filtering with microporous membranes; Filtrate was placed 48 hours down at 5 ℃, was diluted to 500mL with water for injection, 0.1 μ m filtering with microporous membrane, and embedding (2mL/ bottle), lyophilization, radiation sterilization, packing gets final product.
3. the present invention has carried out following pharmacodynamics test to described calcium dobesilate injection and powder needle injection:
(1) the room temperature study on the stability that keeps sample
The results are shown in Table 1; from keeping sample the stability test result for a long time as can be known; be in calcium dobesilate injection under the solution condition in character, clarity and assay project 18 months with interior up to specification; and the calcium dobesilate powder needle injection is owing to be under the protection of solid state and antioxidant, and its effect duration can reach more than 30 months.Therefore, the calcium dobesilate powder needle injection is more stable than solution type injection agent.
(2) sensitivity test and pyrogenic test research
Carry out sensitivity test with calcium dobesilate injection and the powder needle injection of preserving 18 months in the stability test.Detection of drugs is to the anaphylactic reaction of skin and to the temperature influence of rabbit.The sensitivity test of skin is experimental animal with the Cavia porcellus, and pyrogenic test is experimental animal with the rabbit, and for instructing, intravenous injection the results are shown in Table 2 by " new drug preclinical study guideline ".
Conclusion: under commercially available back, 20 ℃ of samples of preserving 18 months, calcium dobesilate injection and powder needle injection do not have skin allergy, do not have thermal source (or foreign body) yet and cause rabbit body temperature to raise.
(3) pharmacological testing
Adopt the varied in thickness of calcium dobesilate injection and powder needle injection treatment macular area neuroepithelium of retina to the results are shown in Table 3 respectively.Change very remarkable (P＜0.01) before and after the treatment of macular area neuroepithelium of retina thickness as seen from table.
The table 1 room temperature study on the stability experimental result that keeps sample
| The investigation time | Reserved sample observing (temperature; 20 ℃, humidity; 75%) | ||||||
| Calcium dobesilate injection | The calcium dobesilate powder needle injection | ||||||
| Character | Clarity | Content | Character | Clarity | Content | ||
| First | 0th month | - | - | - | - | - | - |
| 6th month | - | - | - | - | - | - | |
| 12nd month | - | - | - | - | - | - | |
| 18th month | - | - | - | - | - | - | |
| 24th month | - | + | + | - | - | - | |
| 36th month | - | + | + | - | - | - | |
| Second batch | 0th month | - | - | - | - | - | - |
| 6th month | - | - | - | - | - | - | |
| 12nd month | - | - | - | - | - | - | |
| 18th month | - | - | - | - | - | - | |
| 24th month | - | + | + | - | - | - | |
| 36th month | - | + | + | - | - | - | |
| The 3rd batch | 0th month | - | - | - | - | - | - |
| 6th month | - | - | - | - | - | - | |
| 12nd month | - | - | - | - | - | - | |
| 18th month | - | - | - | - | - | - | |
| 24th month | - | + | + | - | - | - | |
| 36th month | - | + | + | - | - | - | |
Annotate: this inspection item conformance with standard of-expression; These inspection item of+expression do not meet standard.
Table 2. hypersensitive test and pyrogenic test are investigated the result
| Inspection item | The calcium dobesilate injection | The calcium dobesilate powder needle injection | ||||
| Lot number 1 | Lot number 2 | Lot number 3 | Lot number 1 | Lot number 2 | Lot number 3 | |
| Skin | - | - | - | - | - | + |
| Body temperature changes | - | - | - | - | - | - |
Annotate: (1) hypersensitive test evaluation index
The no erythema of-expression ,+represent slight erythema, ++ the expression moderate erythema, +++expression severe erythema, ++ ++ represent edematous erythema.
(2) pyrogenic test is changed to evaluation index with body temperature
-expression thermal source is up to the standards ,+expression thermal source disqualified upon inspection.
The varied in thickness (A °) of table 3. calcium dobesilate injection and powder needle injection treatment macular area neuroepithelium of retina
| Medicine | Before the treatment | After the treatment | t | p |
| The calcium dobesilate injection | 461.28±94.29 | 449.27±92.39 | 3.647 | 0.001** |
| The calcium dobesilate injection powder injection | 465.83±96.94 | 499.64±94.35 | -6.824 | 0.001** |
The present invention has following significant advantage;
1. can increase significantly stability of drug products by adding antioxidant among the present invention, prolong expiration date of drug.
2. the present invention is directed to a medicine stability difficult problem, adopt solid injection (powder-injection) technology, improve the stability of medicine.
3. the refrigerating process of the present invention by uniqueness significantly improved injection clarity and stability and improves.
4. the present invention can solve the in great shortage difficult problem of eyeground PVR medicine that present treatment diabetes cause. By the research of formulation, technique and auxiliary material, developed calcium dobesilate injection and powder needle injection, have huge commercial application value.
Claims (7)
1. calcium dobesilate injection and powder needle injection also contain acceptable adjuvant on the pharmaceutics except that containing the principal agent calcium dobesilate.Calcium dobesilate injection and powder needle injection are used for people's retrobulbar injection.
2. calcium dobesilate injection according to claim 1 and powder needle injection, wherein the content of calcium dobesilate is 0.2～20mg/mL, the percentage by weight of acceptable auxiliary is 0～50% on the pharmaceutics.
3. calcium dobesilate injection according to claim 1 and powder needle injection, wherein said powder needle injection are the powder needle injection or the lyophilization powder needle injections of said spraying or hot air drying on any pharmaceutics.
4. calcium dobesilate injection according to claim 1 and powder needle injection, wherein said adjuvant comprises skeleton proppant, antioxidant.
5. calcium dobesilate injection according to claim 4 and powder needle injection, wherein said skeleton proppant is selected from a kind of in mannitol, vitamin C, carbamide, glucose, dextran, polyvidon or the glycine or their mixture.
6. calcium dobesilate injection according to claim 4 and powder needle injection, wherein said antioxidant is selected from a kind of of vitamin C, vitamin E, sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, methionine, thiourea, Calcium Disodium Versenate, citric acid, or their mixture.
7. the application in preparation treatment ophthalmology illness medicine of calcium dobesilate injection according to claim 1 and powder needle injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610046483 CN101062011A (en) | 2006-04-30 | 2006-04-30 | Calcium dobesilate injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610046483 CN101062011A (en) | 2006-04-30 | 2006-04-30 | Calcium dobesilate injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101062011A true CN101062011A (en) | 2007-10-31 |
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ID=38963432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610046483 Pending CN101062011A (en) | 2006-04-30 | 2006-04-30 | Calcium dobesilate injection |
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|---|---|
| CN (1) | CN101062011A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101254174B (en) * | 2007-12-05 | 2010-12-01 | 江苏吴中医药集团有限公司苏州第六制药厂 | Freeze-dried injection containing carbazochrome sodium sulfonate and method of preparing the same |
| CN101849930B (en) * | 2009-03-31 | 2012-04-04 | 符健 | Chemical medicament for treating cardiac and cerebral diseases and preparation method thereof |
| EP2649993A1 (en) * | 2010-12-09 | 2013-10-16 | Maruishi Pharmaceutical Co., Ltd. | Stabilizer of acetaminophen |
| CN105796513A (en) * | 2014-12-31 | 2016-07-27 | 江苏万邦生化医药股份有限公司 | Calcium dobesilate pharmaceutical composition |
| CN106265537A (en) * | 2016-08-26 | 2017-01-04 | 合肥立方制药股份有限公司 | Sodium dimercaptopropanesulfonate freeze-dried powder and preparation method thereof |
| CN109718214A (en) * | 2017-10-27 | 2019-05-07 | 南京长澳医药科技有限公司 | A kind of preparation method of calcium dobesilate |
| CN111481499A (en) * | 2020-05-28 | 2020-08-04 | 湖南通证医药科技有限公司 | Calcium dobesilate gel and preparation method and application thereof |
-
2006
- 2006-04-30 CN CN 200610046483 patent/CN101062011A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101254174B (en) * | 2007-12-05 | 2010-12-01 | 江苏吴中医药集团有限公司苏州第六制药厂 | Freeze-dried injection containing carbazochrome sodium sulfonate and method of preparing the same |
| CN101849930B (en) * | 2009-03-31 | 2012-04-04 | 符健 | Chemical medicament for treating cardiac and cerebral diseases and preparation method thereof |
| EP2649993A1 (en) * | 2010-12-09 | 2013-10-16 | Maruishi Pharmaceutical Co., Ltd. | Stabilizer of acetaminophen |
| EP2649993A4 (en) * | 2010-12-09 | 2014-07-30 | Maruishi Pharma | Stabilizer of acetaminophen |
| US9452216B2 (en) | 2010-12-09 | 2016-09-27 | Maruishi Pharmaceutical Co., Ltd. | Agent for stabilizing acetaminophen |
| CN105796513A (en) * | 2014-12-31 | 2016-07-27 | 江苏万邦生化医药股份有限公司 | Calcium dobesilate pharmaceutical composition |
| CN106265537A (en) * | 2016-08-26 | 2017-01-04 | 合肥立方制药股份有限公司 | Sodium dimercaptopropanesulfonate freeze-dried powder and preparation method thereof |
| CN109718214A (en) * | 2017-10-27 | 2019-05-07 | 南京长澳医药科技有限公司 | A kind of preparation method of calcium dobesilate |
| CN109718214B (en) * | 2017-10-27 | 2022-07-22 | 南京长澳医药科技有限公司 | Preparation method of calcium dobesilate tablets |
| CN111481499A (en) * | 2020-05-28 | 2020-08-04 | 湖南通证医药科技有限公司 | Calcium dobesilate gel and preparation method and application thereof |
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Open date: 20071031 |