CN1158301C - Soluble inorganic salt of Huanweihuangyangxing D, its preparing process and medicine containing it - Google Patents
Soluble inorganic salt of Huanweihuangyangxing D, its preparing process and medicine containing it Download PDFInfo
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- CN1158301C CN1158301C CNB011330589A CN01133058A CN1158301C CN 1158301 C CN1158301 C CN 1158301C CN B011330589 A CNB011330589 A CN B011330589A CN 01133058 A CN01133058 A CN 01133058A CN 1158301 C CN1158301 C CN 1158301C
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- cyclovirobuxinum
- acid
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Abstract
The present invention relates to the water soluble salts of cyclovirobuxinum D, the preparation of the water soluble salts, and a medicinal preparation containing the water soluble salts; more specifically, the present invention relates to the water soluble salts of cyclovirobuxinum D, the preparation of the water soluble salts, an injection containing the water soluble salts, and the application of the injection to treating coronary heart disease and arrhythmia.
Description
Invention field
The present invention relates to the water-soluble salt of cyclovirobuxinum D, its preparation and contain their pharmaceutical preparation.More specifically say, the present invention relates to the water-soluble inorganic salt of cyclovirobuxinum D, its preparation contains their injection and treats coronary heart disease, the purposes in the irregular pulse.
Background technology
Cyclovirobuxinum D is a kind of known organism alkali, and it is the Chinese medicinal materials for including by medicinal material and goods thereof in one one of Chinese Pharmacopoeia (version in 2000).Raise the oral tablet that star D makes and also recorded by version Chinese Pharmacopoeia in 2000 with ring dimension is yellow, and be used for coronary heart disease, ARR treatment.But in clinical use, this cyclovirobuxinum D oral tablet onset is slow, and this is for coronary heart disease, and ARR treatment is very disadvantageous shortcoming.Therefore the result of treatment such as the onset that improve existing cyclovirobuxinum D oral tablet are slow, and the low grade of bioavailability is still very necessary.
Summary of the invention
It is slow that the object of the invention is to improve the onset of existing cyclovirobuxinum D oral tablet, and bioavailability is low to wait deficiency also and then develop new cyclovirobuxinum D preparation.
The inventor is existing after deliberation to find that especially with inorganic salt, salify can improve the water-soluble of cyclovirobuxinum D by cyclovirobuxinum D and acid, and and then salifiable cyclovirobuxinum D is made various preparations such as injection, capsule etc.Salifiable cyclovirobuxinum D demonstrates good onset speed and bioavailability in animal model.The present invention is based on above-mentioned discovery now finishes.
Therefore, first aspect present invention relates to the salt of the cyclovirobuxinum D that forms with acid, and wherein acid is selected from hydrochloric acid, sulfuric acid, Hydrogen bromide or phosphoric acid.
Further aspect of the present invention relates to the salt that contains cyclovirobuxinum D and the pharmaceutical composition of pharmaceutical carrier or thinner, wherein is selected from hydrochloric acid, sulfuric acid, Hydrogen bromide or phosphoric acid with the salifiable acid of cyclovirobuxine.
The present invention relates to the salt that contains cyclovirobuxinum D and the injection of pharmaceutical carrier or vehicle on the other hand, wherein is selected from hydrochloric acid, sulfuric acid, Hydrogen bromide or phosphoric acid with the salifiable acid of cyclovirobuxine.
The present invention relates to cyclovirobuxinum D on the other hand and is selected from hydrochloric acid, sulfuric acid, and the salt that Hydrogen bromide or phosphoric acid become is used for the treatment of purposes in coronary heart disease or the ARR medicine in preparation.
The present invention at first relates to cyclovirobuxinum D and the sour salt that forms, but described acid organic acid or inorganic salt, but preferred inorganic salt, example hydrochloric acid, sulfuric acid, Hydrogen bromide or phosphoric acid, more preferably hydrochloric acid.
Further aspect of the present invention relates to the salt that contains cyclovirobuxinum D and the pharmaceutical composition of pharmaceutical carrier or thinner.
According to the present invention, pharmaceutical composition of the present invention can be taken by various approach, and as enteron aisle, oral or parenteral route is applicable to that the formulation of oral administration has for example: oral liquid, granule, Sublingual tablet, dry suspensoid or pill etc.; The formulation that is suitable for parenterai administration has injection liquid, transfusion etc. for example.The formulation of preferred administration is an injection liquid.
According to the present invention, used pharmaceutical carrier or vehicle or thinner are commonly used those of pharmacy field in the pharmaceutical composition of the present invention, as tackiness agent, and disintegrating agent, lubricant, water for injection etc.
According to the present invention, the preparation of cyclovirobuxinum D salt of the present invention can be by carrying out cyclovirobuxinum D and acid-respons in water easily.In addition, as needs, can cyclovirobuxinum D is refining in advance.
Embodiment
The following examples are used to further specify the present invention, but do not mean that the present invention only limits to this.
Embodiment 1
Synthesizing of cyclovirobuxinum D hydrochloride:
1. cyclovirobuxinum D is refining:
Get cyclovirobuxinum D raw material 15g, put in the 1000ml flask, add the dehydrated alcohol of 225ml, reflux, treat bulk drug dissolve fully after suction filtration while hot, filter residue discards.Get filtrate and place in about 4 ℃ the refrigerator and leave standstill to be crystallized separating out of a night, suction filtration, mother liquor reclaims stand-by.The crystalline solid thing is put 60 ℃ and is drying to obtain cyclovirobuxinum D feed purification product 5.5g, and yield 30.6%. feeds intake for many times, the mother liquor recycling, and total recovery can reach about 90%.
2. the cyclovirobuxinum D hydrochloride is synthetic:
Get cyclovirobuxinum D feed purification product 30g, put in the flask of 1000ml, add 360ml water, heating drips 10% hydrochloric acid, transfers PH to 6, suction filtration while hot, and filter residue discards.Filtrate is placed to leave standstill in about 4 ℃ the refrigerator and is to be crystallizedly gone out a night, suction filtration, and mother liquor reclaims stand-by.The crystalline solid thing is put 60 ℃ and is drying to obtain hydrochloric acid cyclovimbuxine D crude product 22.38g.Yield 63.15%.(repeatedly feed intake, the mother liquor recycling, total recovery can reach about 90%).Then hydrochloric acid cyclovimbuxine D is put in the 500ml beaker, add 80 ℃ of water dissolution after, filter while hot, filtrate is placed leave standstill in about 4 ℃ the refrigerator and to be crystallizedly goes out a night, suction filtration, mother liquor reclaims stand-by.The crystalline solid thing is put 60 ℃ and is drying to obtain hydrochloric acid cyclovimbuxine D highly finished product 17.4g.Yield 37.5%.Infrared absorption spectrum: absorption peak 3418.13,3381.05,2945.02,2869.58,1597.67,1463.42,1422.92,1381.90,913.37; Hydrogen nuclear magnetic resonance: chemical shift 0.45,0.6,0.9,0.9,1.03,1.12,1.15,1.33,1.35,1.40,1.62,1.80,2.1,2.73,2.74,2.90,3.48,4.31.
Embodiment 2
Preparation (the specification: 1mg/1ml) of cyclovirobuxine hydrochloride injection liquid (hydrochloric acid Buxine injection liquid)
2.1 direct preparation method with the cyclovirobuxinum D hydrochloride:
Get cyclovirobuxinum D hydrochloride 1g, add injection water 1000ml, in cleanliness factor is 100 grades clean room,,, make 1000 with the ampoule embedding of 1ml with the membrane filtration of 0.5 μ, flowing steam sterilization 30 minutes, lamp is examined, and injection liquid is made in quality inspection.
2.2 hydrochloric acid is transferred the PH method:
Get cyclovirobuxinum D 1g, add injection water 100ml, stir and make into suspension, till when transferring solution extremely clear and bright with dilute hydrochloric acid (0.1mol/L), filter, the pH value of surveying filtrate is near 5, add the injection water to 1000ml, in cleanliness factor is 100 grades clean room, with the membrane filtration of 0.5 μ, ampoule embedding with 1ml, make 1000, flowing steam sterilization 30 minutes, lamp inspection, injection liquid is made in quality inspection.
Embodiment 3
Preparation (the specification: 1mg/100ml) of cyclovirobuxine hydrochloride injection liquid (hydrochloric acid Buxine injection liquid)
3.1 the direct preparation method of cyclovirobuxinum D hydrochloride:
Get cyclovirobuxinum D hydrochloride 1g, add sodium-chlor 900g, add water for injection 100000ml, stir, in cleanliness factor is 100 grades clean room,,, make 1000 bottles with the infusion bottle embedding of 100ml with the membrane filtration of 0.5 μ, flowing steam sterilization 30 minutes, the lamp inspection, injection liquid is made in quality inspection.
3.2 the accent PH method of hydrochloric acid:
Get cyclovirobuxinum D 1g, add injection water 100ml, stir and make into suspension, till when transferring solution extremely clear and bright with dilute hydrochloric acid (0.1mol/L), filter, the pH value of surveying filtrate is near 5, add water for injection to 100000ml, add sodium-chlor 900g, stir, in cleanliness factor is 100 grades clean room, with the membrane filtration of 0.5 μ, with the infusion bottle embedding of 100ml, make 1000 bottles, flowing steam sterilization 30 minutes, lamp inspection, injection liquid is made in quality inspection.
Claims (6)
1. a cyclovirobuxinum D and the sour salt that forms is characterized in that described acid is selected from hydrochloric acid, sulfuric acid or phosphoric acid.
2. salt according to claim 1 is characterized in that the salt that forms is the cyclovirobuxinum D hydrochloride.
3. a pharmaceutical composition comprises cyclovirobuxinum D and salt and pharmaceutical carrier or vehicle that acid forms, it is characterized in that acid is selected from hydrochloric acid, sulfuric acid or phosphoric acid.
4. according to the described composition of claim 3, it is characterized in that said composition is oral liquid, dry suspensoid or injection liquid.
5. according to the described composition of claim 4, it is characterized in that said composition is an injection liquid.
6. according to the described arbitrary composition of claim 3-5, it is characterized in that the salt that forms is the cyclovirobuxinum D hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011330589A CN1158301C (en) | 2001-09-17 | 2001-09-17 | Soluble inorganic salt of Huanweihuangyangxing D, its preparing process and medicine containing it |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011330589A CN1158301C (en) | 2001-09-17 | 2001-09-17 | Soluble inorganic salt of Huanweihuangyangxing D, its preparing process and medicine containing it |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1379040A CN1379040A (en) | 2002-11-13 |
| CN1158301C true CN1158301C (en) | 2004-07-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB011330589A Expired - Fee Related CN1158301C (en) | 2001-09-17 | 2001-09-17 | Soluble inorganic salt of Huanweihuangyangxing D, its preparing process and medicine containing it |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100391463C (en) * | 2003-05-06 | 2008-06-04 | 天津天士力制药股份有限公司 | Cyclovirobuxine dripping pill and its prepn. process |
| CN100450489C (en) * | 2003-12-11 | 2009-01-14 | 天津天士力制药股份有限公司 | Huangyangning drop pills and preparation method |
| CN100376596C (en) * | 2006-03-13 | 2008-03-26 | 杭太俊 | Buxine, buxine hydrochloride, and its preparing method and formulation |
| CN106632573B (en) * | 2016-12-30 | 2018-09-21 | 江苏晶立信医药科技有限公司 | A kind of preparation method of cyclovimbuxine D hydrochloride |
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2001
- 2001-09-17 CN CNB011330589A patent/CN1158301C/en not_active Expired - Fee Related
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| Publication number | Publication date |
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| CN1379040A (en) | 2002-11-13 |
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