CN104473864A - Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof - Google Patents
Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof Download PDFInfo
- Publication number
- CN104473864A CN104473864A CN201410688237.3A CN201410688237A CN104473864A CN 104473864 A CN104473864 A CN 104473864A CN 201410688237 A CN201410688237 A CN 201410688237A CN 104473864 A CN104473864 A CN 104473864A
- Authority
- CN
- China
- Prior art keywords
- sodium sulfonate
- carbazochrome sodium
- purity
- carbazochrome
- glycerol
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medicines and in particular relates to a carbazochrome sodium sulfonate semisolid preparation and a preparation method thereof. The preparation method comprises the following steps: with high-purity carbazochrome sodium sulfonate with the purity above 99.80 percent as an active ingredient, adding a medical matrix to prepare one of suppository, ointment and gel; wherein every10g of the suppository contains 20-80mg of carbazochrome sodium sulfonate; the ointment per 10g contains 40-80mg of the carbazochrome sodium sulfonate; every 5g of the gel contains 40-80mg of the carbazochrome sodium sulfonate. According to the carbazochrome sodium sulfonate semisolid preparation and the preparation method disclosed by the invention, the purity of the carbazochrome sodium sulfonate serving as the active ingredient is above 99.80 percent and by-products are controlled to be below 0.2 percent; when the carbazochrome sodium sulfonate semisolid preparation is used, the adverse reaction incidence in the medication process can be lowered and the medication safety can be improved; meanwhile, the prepared carbazochrome sodium sulfonate semisolid preparation can be delivered by virtue of body cavities so that the high-purity carbazochrome sodium sulfonate is capable of improving the medication safety while high bioavailability of a product is ensured.
Description
Technical field
The present invention relates to medical art, be specifically related to a kind of carbazochrome sodium sulfonate semi-solid preparation and preparation method thereof.
Background technology
Carbazochrome sodium sulfonate grinds by limit, field Rhizoma Sparganii medicine Co., Ltd. (MITSUBISHI TANABE company) is former, now recorded into Pharmacopeia of Japan the 12 edition by Japanese health ministry, chemical name is: 1-methyl-6-oxo-2,3,5,6-tetrahydro indole-5-semicarbazone-2-sodium sulfonate.
Carbazochrome sodium sulfonate is hemorrhage of new generation, for the derivant of carbazochrome salicylate (carbazochrome salicylate), it introduces sodium group on molecular structure, and the dissolubility overcoming carbazochrome salicylate is little, must, by the shortcoming of salicylic acid hydrotropy, make this compound create obvious haemostatic effect.
Carbazochrome sodium sulfonate can reduce the permeability of blood capillary, promote the retraction effect of blood capillary fracture end, increase the resistance of blood capillary to damage, stablize the acid mucopolysaccharide of blood capillary and surrounding tissue, promote the activity of thrombin and thrombin and fibrinogenic dissolving, hemorrhage for urinary system, upper digestive tract, respiratory tract and obstetrical and gynecological disease.Comparatively remarkable to urinary system bleeding, also can be used for wound and operative hemorrhage.
The carbazochrome sodium sulfonate of current domestic approval listing is all in use with the form of injection, have injection carbazochrome sodium sulfonate, carbazochrome sodium sulfonate for injection, carbazochrime sodium sulfonate injection, carbazochrome sodium sulfonate sheet, wherein especially with injection related preparations listing producer many, be widely used.But some by-products produced in carbazochrome sodium sulfonate injection building-up process can cause patient to occur feeling sick, the untoward reaction such as dizzy and injection site is red, pain.
Meanwhile, also have part oral tablet, after entering in the intestines and stomach, the gastric acid in gastric juice can react with it, destroys the result of use of carbazochrome sodium sulfonate tablet.Consider the application prospect of this carbazochrome sodium sulfonate, need to provide one can effectively overcome prior art shortcoming, and provide a kind of brand-new carbazochrome sodium sulfonate semi-solid preparation imperative.In view of this, special proposition the present invention.
Summary of the invention
The first object of the present invention is to provide a kind of carbazochrome sodium sulfonate semi-solid preparation, adopts administration in body cavities, and while guarantee product bioavailability, high-purity carbazochrome sodium sulfonate can improve the safety of medication, and carbazochrome sodium sulfonate is used widely.
The second object of the present invention there are provided a kind of preparation method of high-purity carbazochrome sodium sulfonate semi-solid preparation.
In order to realize above-mentioned purpose of the present invention, spy by the following technical solutions:
A kind of high-purity carbazochrome sodium sulfonate semi-solid preparation, with the high-purity carbazochrome sodium sulfonate of purity more than 99.80% for effective ingredient, adds the one in suppository that medicinal substrate makes, ointment, gel;
Suppository described in every 10g is containing carbazochrome sodium sulfonate 20 ~ 80mg; Containing carbazochrome sodium sulfonate 40-80mg in ointment described in every 10g; Containing carbazochrome sodium sulfonate 40-80mg in gel described in every 5g.
Semi-solid preparation containing high-purity carbazochrome sodium sulfonate prepared by the present invention, its active component carbazochrome sodium sulfonate purity is more than 99.80%, by-product controls below 0.2%, use high-purity carbazochrome sodium sulfonate preparation provided by the invention can reduce adverse reaction rate in medication process, and can drug safety be improved.The carbazochrome sodium sulfonate semi-solid preparation simultaneously made, can by administration in body cavities, and while guarantee product bioavailability, high-purity carbazochrome sodium sulfonate can improve the safety of medication.
On above technical scheme basis, the present invention can also do following improvement.
Further, described medicinal substrate is one or more combination of excipient, surfactant, absorbent, diluent, lubricant, antiseptic.
Further, the medicinal substrate used in described suppository is: gelatin, purified water, Polyethylene Glycol, glycerol, wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: gelatin 7.5-50 part, purified water 25-150 part, Polyethylene Glycol (400) 2.5-30 part, glycerol 50-200 part.Wherein, gelatin, purified water, Polyethylene Glycol, glycerol are the substrate of suppository, for carrying the material that may be formed into bolt of active component, use above-mentioned substrate can not only ensure the stability of suppository in suppository, are easy to preserve; And in use can under the effect of body temperature flash melt, improve medication efficiency.
Further, the medicinal substrate used in described ointment is: glyceryl monostearate, white vaseline, glycerol, sodium lauryl sulphate, ethyl hydroxybenzoate, benzalkonium bromide solution, dimethyl sulfoxide, cetostearyl alcohol and purified water; Wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: glyceryl monostearate 6-50 part, white vaseline 6-50 part, glycerol 6-50 part, sodium lauryl sulphate 1-10 part, ethyl hydroxybenzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide 2.5-10 part, cetostearyl alcohol 6-50 part, purified water 25-150 part.Wherein, glyceryl monostearate, sodium lauryl sulphate, benzalkonium bromide solution are surfactant, playing emulsification, white vaseline is that lubricant and glycerol are diluent, ethyl hydroxybenzoate is antiseptic, dimethyl sulfoxide is diluent, play dissolved matrix, above-mentioned substrate is used in ointment, high-purity carbazochrome sodium sulfonate ointment can not only be kept to be not easy in for a long time oxidized, and be easy to absorb.
Further, the medicinal substrate used in described gel is: viscosity is carbomer, triethanolamine, glycerol, the ethyl hydroxybenzoate of 934; Wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerol 2.5-25 part, ethyl hydroxybenzoate 0.1-0.25 part.Wherein, viscosity is the carbomer of 934 and glycerol is substrate, triethanolamine is surfactant, plays emulsifying, the effect of moisturizing, ethyl hydroxybenzoate be antiseptic, use above-mentioned substrate as the substrate of gel, not only not easily oxidized, be easy to preserve and use, and it is fast to be easy to infiltration rate.
Present invention also offers the method preparing aforesaid a kind of carbazochrome sodium sulfonate semi-solid preparation, described high-purity carbazochrome sodium sulfonate and described medicinal substrate are mixed and made into described carbazochrome sodium sulfonate semi-solid preparation.
Further, the method preparing described suppository comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: gelatin 7.5-50 part, purified water 25-150 part, Polyethylene Glycol (400) 2.5-30 part, glycerol 50-200 part; Suppository described in every 10g is containing carbazochrome sodium sulfonate 20 ~ 80mg;
According to described number, get gelatin, add purified water, place and within 22-24 hour, make its abundant moistening, then add glycerol and the Polyethylene Glycol (400) of proportional quantity, heating for dissolving mix homogeneously is as substrate; After measuring described medicinal substrate and adding the high-purity carbazochrome sodium sulfonate mix homogeneously of proportional quantity, after 70 DEG C of deaeration 2-3 hours, to be poured in mould cooled and solidified and to get final product.
Further, the method preparing described ointment comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: glyceryl monostearate 6-50 part, white vaseline 6-50 part, glycerol 6-50 part, sodium lauryl sulphate 1-10 part, ethyl hydroxybenzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide 2.5-10 part, cetostearyl alcohol 6-50 part; Purified water 25-150 part; ; Containing carbazochrome sodium sulfonate 40-80mg in ointment described in every 10g;
According to described number, mix to obtain aqueous phase by glycerol, sodium lauryl sulphate, ethyl hydroxybenzoate, dimethyl sulfoxide, purified water, benzalkonium bromide solution and high-purity carbazochrome sodium sulfonate 100 DEG C; In proportion cetostearyl alcohol, glyceryl monostearate and white vaseline are mixed to obtain oil phase at 90-95 DEG C; After aqueous phase and oil phase emulsifying, homogenizing, cooling, embedding and get final product.
Further, the method preparing described gel comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: viscosity be 934 carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerol 2.5-25 part, ethyl hydroxybenzoate 0.1-0.25 part, purified water 25-150 part; Containing carbazochrome sodium sulfonate 40-80mg in gel described in every 5g;
According to described number, get viscosity be 934 carbomer to be evenly spread on purified water surface fully swelling, then add triethanolamine and stir, adjust ph is 5 ~ 6, obtains substrate; Get the high-purity carbazochrome sodium sulfonate of proportional quantity, glycerol, ethyl hydroxybenzoate mixing, add gradually in the substrate under stirring, then after adding purified water mixing, embedding and get final product.
Further, the high-purity carbazochrome sodium sulfonate of purity more than 99.80%, its preparation method comprises the following steps:
Step 1, in the reaction vessel that mechanical agitator is housed, add sodium sulfite and deionized water with the speed stirring and dissolving of 70.0 ~ 80.0r/min, add recipe quantity Adenaron again, control reactant liquor at 15.0 ~ 25.0 DEG C with the speed stirring reaction of 50.0 ~ 60.0r/min, after having orange/yellow solid to separate out, continue stirring 3 ~ 5 hours, filter, precipitate to obtain carbazochrome sodium sulfonate crude product;
Step 2, the deionized water adding gained carbazochrome sodium sulfonate crude product and 10.0 ~ 15.0 times of quality in churned mechanically reaction bulb is being housed, stir with the speed of 50.0 ~ 60.0r/min and be heated to solvent refluxing, after dissolution of solid, add recipe quantity active carbon, continue stirring and refluxing 30 ~ 60 minutes, filtered while hot, filtrate is slowly reduced to room temperature crystallize 30-35 minute, filter, drying under reduced pressure 4-6 hour at being deposited in 60.0 DEG C, obtains high-purity carbazochrome sodium sulfonate.
Compared with prior art, beneficial effect of the present invention is:
1. the present invention prepare containing the semi-solid preparation of high-purity carbazochrome sodium sulfonate, its active component carbazochrome sodium sulfonate purity is more than 99.80%, by-product controls below 0.2%, uses high-purity carbazochrome sodium sulfonate preparation to reduce adverse reaction rate, improves drug safety.
2. the semi-solid preparation containing high-purity carbazochrome sodium sulfonate that prepared by the present invention is cavity/canal drug administration, compared with other oral solid formulations, avoids carbazochrome sodium sulfonate by stomach acids destroy, absorbs rapidly after entering body cavities, play local action, ensure that product curative effect.
3. medication is convenient, and patient can medication voluntarily, need not rely on medical personnel.
Detailed description of the invention
Below in conjunction with embodiment, embodiment of the present invention are described in detail, but it will be understood to those of skill in the art that the following example only for illustration of the present invention, and should not be considered as limiting the scope of the invention.Unreceipted actual conditions person in embodiment, the condition of conveniently conditioned disjunction manufacturer suggestion is carried out.Agents useful for same or the unreceipted production firm person of instrument, be and can buy by commercially available the conventional products obtained.
A kind of high-purity carbazochrome sodium sulfonate semi-solid preparation, with the high-purity carbazochrome sodium sulfonate of purity more than 99.80% for effective ingredient, adds the one in suppository that medicinal substrate makes, ointment, gel;
Suppository described in every 10g is containing carbazochrome sodium sulfonate 20 ~ 80mg; Containing carbazochrome sodium sulfonate 40-80mg in ointment described in every 10g; Containing carbazochrome sodium sulfonate 40-80mg in gel described in every 5g.
Semi-solid preparation containing high-purity carbazochrome sodium sulfonate prepared by the present invention, its active component carbazochrome sodium sulfonate purity is more than 99.80%, by-product controls below 0.2%, use high-purity carbazochrome sodium sulfonate preparation provided by the invention can reduce adverse reaction rate in medication process, and can drug safety be improved.The carbazochrome sodium sulfonate semi-solid preparation simultaneously made, can by administration in body cavities, and while guarantee product bioavailability, high-purity carbazochrome sodium sulfonate can improve the safety of medication.
On above technical scheme basis, the present invention can also do following improvement.
Further, described medicinal substrate is one or more combination of excipient, surfactant, absorbent, diluent, lubricant, antiseptic.
Further, the medicinal substrate used in described suppository is: gelatin, purified water, Polyethylene Glycol, glycerol, wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: gelatin 7.5-50 part, purified water 25-150 part, Polyethylene Glycol (400) 2.5-30 part, glycerol 50-200 part.Wherein, gelatin, purified water, Polyethylene Glycol, glycerol are the substrate of suppository, for carrying the material that may be formed into bolt of active component, use above-mentioned substrate can not only ensure the stability of suppository in suppository, are easy to preserve; And in use can under the effect of body temperature flash melt, improve medication efficiency.
Further, the medicinal substrate used in described ointment is: glyceryl monostearate, white vaseline, glycerol, sodium lauryl sulphate, ethyl hydroxybenzoate, benzalkonium bromide solution, dimethyl sulfoxide, cetostearyl alcohol and purified water; Wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: glyceryl monostearate 6-50 part, white vaseline 6-50 part, glycerol 6-50 part, sodium lauryl sulphate 1-10 part, ethyl hydroxybenzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide 2.5-10 part, cetostearyl alcohol 6-50 part, purified water 25-150 part.Wherein, glyceryl monostearate, sodium lauryl sulphate, benzalkonium bromide solution are surfactant, play emulsification, white vaseline and glycerol and be substrate), ethyl hydroxybenzoate is antiseptic, dimethyl sulfoxide is diluent, play dissolved matrix, above-mentioned substrate is used in ointment, high-purity carbazochrome sodium sulfonate ointment can not only be kept to be not easy in for a long time oxidized, and be easy to absorb.
Further, the medicinal substrate used in described gel is: viscosity is carbomer, triethanolamine, glycerol, the ethyl hydroxybenzoate of 934; Wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerol 2.5-25 part, ethyl hydroxybenzoate 0.1-0.25 part.Wherein, viscosity is the carbomer of 934 and glycerol is substrate, triethanolamine is emulsifying agent, plays emulsifying, the effect of moisturizing, ethyl hydroxybenzoate be antiseptic, use above-mentioned substrate as the substrate of gel, not only not easily oxidized, be easy to preserve and use, and it is fast to be easy to infiltration rate.
Present invention also offers the method preparing aforesaid a kind of carbazochrome sodium sulfonate semi-solid preparation, described high-purity carbazochrome sodium sulfonate and described medicinal substrate are mixed and made into described carbazochrome sodium sulfonate semi-solid preparation.
Further, the method preparing described suppository comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: gelatin 7.5-50 part, purified water 25-150 part, Polyethylene Glycol (400) 2.5-30 part, glycerol 50-200 part; Suppository described in every 10g is containing carbazochrome sodium sulfonate 20 ~ 80mg;
According to described number, get gelatin, add purified water, place and within 22-24 hour, make its abundant moistening, then add glycerol and the Polyethylene Glycol (400) of proportional quantity, heating for dissolving mix homogeneously is as substrate; After measuring described medicinal substrate and adding the high-purity carbazochrome sodium sulfonate mix homogeneously of proportional quantity, after 70 DEG C of deaeration 2-3 hours, to be poured in mould cooled and solidified and to get final product.
Further, the method preparing described ointment comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: glyceryl monostearate 6-50 part, white vaseline 6-50 part, glycerol 6-50 part, sodium lauryl sulphate 1-10 part, ethyl hydroxybenzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide 2.5-10 part; Cetostearyl alcohol 6-50 part; Purified water 25-150 part; Containing carbazochrome sodium sulfonate 40-80mg in ointment described in every 10g;
According to described number, mix to obtain aqueous phase by glycerol, sodium lauryl sulphate, ethyl hydroxybenzoate, dimethyl sulfoxide, purified water, benzalkonium bromide solution and high-purity carbazochrome sodium sulfonate 100 DEG C; In proportion cetostearyl alcohol, glyceryl monostearate and white vaseline are mixed to obtain oil phase at 90-95 DEG C; After aqueous phase and oil phase emulsifying, homogenizing, cooling, embedding and get final product.
Further, the method preparing described gel comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: viscosity be 934 carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerol 2.5-25 part, ethyl hydroxybenzoate 0.1-0.25 part, Purified Water q. s 25-150 part; Containing carbazochrome sodium sulfonate 40-80mg in gel described in every 5g;
According to described number, get viscosity be 934 carbomer to be evenly spread on purified water surface fully swelling, then add triethanolamine and stir, adjust ph is 5 ~ 6, obtains substrate; Get the high-purity carbazochrome sodium sulfonate of proportional quantity, glycerol, ethyl hydroxybenzoate mixing, add gradually in the substrate under stirring, then after adding purified water mixing, embedding and get final product.
Further, the high-purity carbazochrome sodium sulfonate of purity more than 99.80%, its preparation method comprises the following steps:
Step 1, in the reaction vessel that mechanical agitator is housed, add sodium sulfite 20.8 parts and deionized water 100ml, with the speed stirring and dissolving of 70.0 ~ 80.0r/min, add Adenaron 23.6 parts again, control reactant liquor at 15.0 ~ 25.0 DEG C with the speed stirring reaction of 50.0 ~ 60.0r/min, after having orange/yellow solid to separate out, continue stirring 3 ~ 5 hours, filter, precipitate to obtain carbazochrome sodium sulfonate crude product;
Step 2, the deionized water adding gained carbazochrome sodium sulfonate crude product and 10.0 ~ 15.0 times of quality in churned mechanically reaction bulb is being housed, stir with the speed of 50.0 ~ 60.0r/min and be heated to solvent refluxing, after dissolution of solid, add active carbon 1.0 parts, continue stirring and refluxing 30 ~ 60 minutes, filtered while hot, filtrate is slowly reduced to room temperature crystallize 30-35 minute, filter, drying under reduced pressure 4-6 hour at being deposited in 60.0 DEG C, obtains high-purity carbazochrome sodium sulfonate.
Embodiment 1: prepare carbazochrome sodium sulfonate suppository 1
Add sodium sulfite 20.8g, purified water 100mL being equipped with in churned mechanically 250mL reaction bulb, stir (75r/min) to dissolving, mixing speed is down to 55.0r/min, adding psychrolusia temperature control makes reacting liquid temperature at 18.0 DEG C ~ 19.0 DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 3 hours, filter, obtain orange-yellow carbazochrome sodium sulfonate crude product 41.6g.
41.6g crude product and 416g purified water is added being equipped with in churned mechanically 500mL reaction bulb in reactor, stir (53.r/min) and be heated to solvent refluxing, after dissolution of solid, add 1.0g active carbon, continue stirring and refluxing 30 minutes, filtered while hot, filtrate is slowly reduced to 14 DEG C, crystallize 30 minutes, filters, be deposited in 60 DEG C of forced air dryings 6 hours, obtain carbazochrome sodium sulfonate fine work 32.1g.
Detect through HPLC, Adenaron is 0.05%, and except Adenaron, each impurity is 0.08%, and carbazochrome sodium sulfonate related substance is 0.13%.
Prepared by suppository: get gelatin 40g, add purified water 120g, place and within 24 hours, make its abundant moistening, add glycerol 100g and PEG400 20g, heating for dissolving mix homogeneously is as substrate, get after 175g substrate adds high-purity carbazochrome sodium sulfonate 1g mix homogeneously, 70 DEG C of deaerations 2 hours, be poured in vaginal suppository mould, cooling, solidify, obtain 50 pieces, carbazochrome sodium sulfonate bolt.
Embodiment 2 prepares carbazochrome sodium sulfonate suppository 2
Add sodium sulfite 20.8g, purified water 100mL being equipped with in churned mechanically 250mL reaction bulb, stir (70r/min) to dissolving, mixing speed is down to 55.6r/min, adding psychrolusia temperature control makes reacting liquid temperature at 18.5 DEG C ~ 19.5 DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 3.5 hours, filter, obtain orange-yellow carbazochrome sodium sulfonate crude product 41.8g.
41.8g crude product and 418g purified water is added being equipped with in churned mechanically 500mL reaction bulb in reactor, stir (55.5r/min) and be heated to solvent refluxing, after dissolution of solid, add 1.0g active carbon, continue stirring and refluxing 30 minutes, filtered while hot, filtrate is slowly reduced to 14.5 DEG C, crystallize 30 minutes, filters, be deposited in 60 DEG C of forced air dryings 5.5 hours, obtain carbazochrome sodium sulfonate fine work 32.4g.
Detect through HPLC, Adenaron is 0.04%, and except Adenaron, each impurity is 0.08%, and carbazochrome sodium sulfonate related substance is 0.14%.
Prepared by suppository: get gelatin 40g, add purified water 120g, place and within 24 hours, make its abundant moistening, add glycerol 100g and PEG400 20g, heating for dissolving mix homogeneously is as substrate, get after 175g substrate adds high-purity carbazochrome sodium sulfonate 2g mix homogeneously, 70 DEG C of deaerations 2 hours, be poured in vaginal suppository mould, cooling, solidify, obtain 50 pieces, carbazochrome sodium sulfonate bolt.
Embodiment 3: prepare carbazochrome sodium sulfonate ointment 1
Add sodium sulfite 20.8g, purified water 100mL being equipped with in churned mechanically 250mL reaction bulb, stir (73r/min) to dissolving, mixing speed is down to 56.1r/min, adding psychrolusia temperature control makes reacting liquid temperature at 19.0 DEG C ~ 20.0 DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 4.0 hours, filter, obtain orange-yellow carbazochrome sodium sulfonate crude product 41.2g.
41.2g crude product and 412g purified water is added being equipped with in churned mechanically 500mL reaction bulb in reactor, stir (56.1r/min) and be heated to solvent refluxing, after dissolution of solid, add 1.0g active carbon, continue stirring and refluxing 30 minutes, filtered while hot, filtrate is slowly reduced to 15.2 DEG C, crystallize 30 minutes, filters, be deposited in 60 DEG C of forced air dryings 5 hours, obtain carbazochrome sodium sulfonate fine work 32.5g.
Detect through HPLC, Adenaron is 0.04%, and except Adenaron, each impurity is 0.07%, and carbazochrome sodium sulfonate related substance is 0.11%.
Prepared by ointment: glycerol 100.0g, sodium lauryl sulphate 20.0g, ethyl hydroxybenzoate 5.0g, dimethyl sulfoxide 20.0g, benzalkonium bromide solution 10.0g purified water 550.0g and high-purity carbazochrome sodium sulfonate 8g are mixed to obtain aqueous phase at 100 DEG C; Cetostearyl alcohol 100.0g, glyceryl monostearate 100.0g and white vaseline 100.0g are mixed 30 minutes at 95 DEG C and obtains oil phase; By aqueous phase and oil phase, vacuum in emulsion tank is stir 30 minutes under 0.05MPa, and then homogenizing (3000r/min) 35 minutes, is cooled to 50 DEG C, and namely embedding obtains carbazochrome sodium sulfonate ointment 200.
Embodiment 4: prepare carbazochrome sodium sulfonate ointment 2
Add sodium sulfite 20.8g, purified water 100mL being equipped with in churned mechanically 250mL reaction bulb, stir (77r/min) to dissolving, mixing speed is down to 56.5r/min, adding psychrolusia temperature control makes reacting liquid temperature at 18.3 DEG C ~ 19.5 DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 4.5 hours, filter, obtain orange-yellow carbazochrome sodium sulfonate crude product 41.4g.
41.4g crude product and 414g purified water is added being equipped with in churned mechanically 500mL reaction bulb in reactor, stir (56.5r/min) and be heated to solvent refluxing, after dissolution of solid, add 1.0g active carbon, continue stirring and refluxing 30 minutes, filtered while hot, filtrate is slowly reduced to 15.5 DEG C, crystallize 30 minutes, filters, be deposited in 60 DEG C of forced air dryings 5.5 hours, obtain carbazochrome sodium sulfonate fine work 32.1g.
Detect through HPLC, Adenaron is 0.04%, and except Adenaron, each impurity is 0.08%, and carbazochrome sodium sulfonate related substance is 0.12%.
Prepared by ointment: glycerol 100.0g, sodium lauryl sulphate 20.0g, ethyl hydroxybenzoate 5.0g, dimethyl sulfoxide 20.0g, benzalkonium bromide solution 10.0g purified water 550.0g and high-purity carbazochrome sodium sulfonate 16g are mixed to obtain aqueous phase at 100 DEG C; Cetostearyl alcohol 100.0g, glyceryl monostearate 100.0g and white vaseline 100.0g are mixed 30 minutes at 95 DEG C and obtains oil phase; By aqueous phase and oil phase, vacuum in emulsion tank is stir 30 minutes under 0.05MPa, and then homogenizing (3000r/min) 35 minutes, is cooled to 50 DEG C, and namely embedding obtains carbazochrome sodium sulfonate ointment 200.
Embodiment 5: prepare carbazochrome sodium sulfonate gel 1
Add sodium sulfite 20.8g, purified water 100mL being equipped with in churned mechanically 250mL reaction bulb, stir (78r/min) to dissolving, mixing speed is down to 56.5r/min, adding psychrolusia temperature control makes reacting liquid temperature at 18.5 DEG C ~ 19.5 DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 4.5 hours, filter, obtain orange-yellow carbazochrome sodium sulfonate crude product 41.3g.
41.3g crude product and 413g purified water is added being equipped with in churned mechanically 500mL reaction bulb in reactor, stir (56.5r/min) and be heated to solvent refluxing, after dissolution of solid, add 1.0g active carbon, continue stirring and refluxing 30 minutes, filtered while hot, filtrate is slowly reduced to 16.0 DEG C, crystallize 30 minutes, filters, be deposited in 60 DEG C of forced air dryings 5.0 hours, obtain carbazochrome sodium sulfonate fine work 32.2g.
Detect through HPLC, Adenaron is 0.04%, and except Adenaron, each impurity is 0.08%, and carbazochrome sodium sulfonate related substance is 0.12%.
Prepare gel: get 10.0g carbomer 934 and be evenly spread on 600.0g purified water surface, place 40 ~ 45 hours fully swelling 4.0g tri-ethanol that adds again and stir, adjust pH5 ~ 6, obtain substrate; Get high-purity carbazochrome sodium sulfonate 8.0g, glycerol 120.0g, ethyl hydroxybenzoate 1.0g mixes, add gradually in the substrate under stirring, then after adding the mixing of 250.0g purified water, embedding obtains carbazochrome sodium sulfonate gel 200.
Embodiment 6: prepare carbazochrome sodium sulfonate gel 2
Add sodium sulfite 20.8g, purified water 100mL being equipped with in churned mechanically 250mL reaction bulb, stir (80r/min) to dissolving, mixing speed is down to 56.8r/min, adding psychrolusia temperature control makes reacting liquid temperature at 18.5 DEG C ~ 20.0 DEG C, add Adenaron 23.6g, have orange/yellow solid to separate out, continue stirring 5.0 hours, filter, obtain orange-yellow carbazochrome sodium sulfonate crude product 41.5g.
41.5g crude product and 415g purified water is added being equipped with in churned mechanically 500mL reaction bulb in reactor, stir (56.8r/min) and be heated to solvent refluxing, after dissolution of solid, add 1.0g active carbon, continue stirring and refluxing 30 minutes, filtered while hot, filtrate is slowly reduced to 16.0 DEG C, crystallize 30 minutes, filters, be deposited in 60 DEG C of forced air dryings 5.5 hours, obtain carbazochrome sodium sulfonate fine work 32.3g.
Detect through HPLC, Adenaron is 0.03%, and except Adenaron, each impurity is 0.08%, and carbazochrome sodium sulfonate related substance is 0.11%.
Prepare gel: get 10.0g carbomer 934 and be evenly spread on 600.0g purified water surface, place 40 ~ 45 hours fully swelling 4.0g tri-ethanol that adds again and stir, adjust pH5 ~ 6, obtain substrate; Get high-purity carbazochrome sodium sulfonate 16.0g, glycerol 120.0g, ethyl hydroxybenzoate 1.0g mixes, add gradually in the substrate under stirring, then after adding the mixing of 250.0g purified water, embedding obtains carbazochrome sodium sulfonate gel 200.
Experimental example 1
The HPLC related in the embodiment of the present invention detects and adopts following detection method:
Chromatographic condition:
Chromatographic column: C
18((250mm × 4.6mm, 5 μm)
Mobile phase: 0.12% Ammonium biphosphate-acetonitrile (91:9, pH=3.0)
Flow velocity: 1.0mL/min
Column temperature: 30.0 DEG C
Determined wavelength: 363nm
Theoretical cam curve is no less than 3000
Algoscopy: get this product 25-150 part, accurately weighed, add mobile phase and dissolve and quantitatively dilute the solution made every 1mL and about contain 0.5mg, as need testing solution, precision measures 0.1mL, puts in 100mL measuring bottle, is diluted with water to scale, shake up, in contrast solution, separately get Adenaron reference substance and be about 25mg, accurately weighed, put in 50mL measuring bottle, scale is diluted to dissolve with methanol, shake up, precision measures 0.1mL, put in 100mL measuring bottle, be diluted with water to scale, spectrometer, regulate detection sensitivity, the peak height of main constituent chromatographic peak is made to be 25% of full scale, precision measures need testing solution and each 20 μ l of Adenaron reference substance solution again, injection liquid chromatography respectively, record chromatogram is to 2 times of main constituent peak retention time, as aobvious impurity peaks in the chromatogram of need testing solution, Adenaron must not calculate 0.1% with peak area by external standard method, the peak area of other single impurity must not be greater than 1/2 (0.05%) of contrast solution main peak area, except Adenaron each impurity peak area and contrast solution main peak area (0.1%) must not be greater than.
Experimental example 2: high-purity carbazochrome sodium sulfonate semi-solid preparation clinical observation
Method: the patient of 81 routine clinical definite digestive tract hemorrhage is divided at random treatment group 41 example, matched group 40 example, respectively high-purity carbazochrome sodium sulfonate bolt and commercially available carbazochrome sodium sulfonate sheet, use 15 days continuously, period stops other treatment.
(1) criterion of therapeutical effect:
Cure: condition of illness sign disappears, and lab testing is normal;
Effective: condition of illness sign does not disappear completely, and lab testing is improved;
Invalid: unchanged before and after the treatment of condition of illness, sign and lab testing.
(2) safety criterion:
Safety: have no untoward reaction symptom
General: slight appearance is felt sick, vertigo symptoms, has no other extremely
Dangerous: to occur comparatively serious adverse reaction symptom and other abnormal responses
(3) observed result: two groups of clinical efficacies are in table 1, and two groups of clinical drug safety are in table 2.
Table 1 high-purity carbazochrome sodium sulfonate suppository clinical observation on the therapeutic effect
Table 2 high-purity carbazochrome sodium sulfonate suppository clinical safety is observed
As can be seen from the above table, preparation of the present invention clinically, obtains good curative effect, 41 patients take preparation of the present invention and have no untoward reaction after 15 days, obtain the therapeutic effect better than tablet, and described preparation has no untoward reaction, tablet produces the general untoward reaction of 5%.
Although illustrate and describe the present invention with specific embodiment, however it will be appreciated that can to make when not deviating from the spirit and scope of the present invention many other change and amendment.Therefore, this means to comprise all such changes and modifications belonged in the scope of the invention in the following claims.
Claims (10)
1. a carbazochrome sodium sulfonate semi-solid preparation, is characterized in that, with the high-purity carbazochrome sodium sulfonate of purity more than 99.80% for effective ingredient, adds the one in suppository that medicinal substrate makes, ointment, gel;
Suppository described in every 10g is containing carbazochrome sodium sulfonate 20 ~ 80mg; Containing carbazochrome sodium sulfonate 40-80mg in ointment described in every 10g; Containing carbazochrome sodium sulfonate 40-80mg in gel described in every 5g.
2. carbazochrome sodium sulfonate semi-solid preparation according to claim 1, it is characterized in that, described medicinal substrate is one or more combination of surfactant, diluent, lubricant, antiseptic.
3. carbazochrome sodium sulfonate semi-solid preparation according to claim 2, it is characterized in that, the medicinal substrate used in described suppository is: gelatin, purified water, Polyethylene Glycol, glycerol, wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: gelatin 7.5-50 part, purified water 25-150 part, Polyethylene Glycol (400) 2.5-30 part, glycerol 50-200 part.
4. carbazochrome sodium sulfonate semi-solid preparation according to claim 2, it is characterized in that, the medicinal substrate used in described ointment is: glyceryl monostearate, white vaseline, glycerol, sodium lauryl sulphate, ethyl hydroxybenzoate, benzalkonium bromide solution, dimethyl sulfoxide, cetostearyl alcohol and purified water; Wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: glyceryl monostearate 6-50 part, white vaseline 6-50 part, glycerol 6-50 part, sodium lauryl sulphate 1-10 part, ethyl hydroxybenzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide 2.5-10 part, cetostearyl alcohol 6-50 part, purified water 25-150 part.
5. carbazochrome sodium sulfonate semi-solid preparation according to claim 2, it is characterized in that, the medicinal substrate used in described gel is: viscosity is carbomer, triethanolamine, glycerol, the ethyl hydroxybenzoate of 934; Wherein, the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerol 2.5-25 part, ethyl hydroxybenzoate 0.1-0.25 part.
6. prepare the method for a kind of carbazochrome sodium sulfonate semi-solid preparation described in any one of claim 1-5, it is characterized in that, described high-purity carbazochrome sodium sulfonate and described medicinal substrate are mixed and made into described carbazochrome sodium sulfonate semi-solid preparation.
7. the method for a kind of carbazochrome sodium sulfonate semi-solid preparation of preparation according to claim 6, is characterized in that,
The method preparing described suppository comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: gelatin 7.5-50 part, purified water 25-150 part, Polyethylene Glycol (400) 2.5-30 part, glycerol 50-200 part; Suppository described in every 10g is containing carbazochrome sodium sulfonate 20 ~ 80mg;
According to described number, get gelatin, add purified water, place and within 22-24 hour, make its abundant moistening, then add glycerol and the Polyethylene Glycol (400) of proportional quantity, heating for dissolving mix homogeneously is as substrate; After measuring described medicinal substrate and adding the high-purity carbazochrome sodium sulfonate mix homogeneously of proportional quantity, after 70 DEG C of deaeration 2-3 hours, to be poured in mould cooled and solidified and to get final product.
8. the method for a kind of carbazochrome sodium sulfonate semi-solid preparation of preparation according to claim 7, is characterized in that,
The method preparing described ointment comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: glyceryl monostearate 6-50 part, white vaseline 6-50 part, glycerol 6-50 part, sodium lauryl sulphate 1-10 part, ethyl hydroxybenzoate 0.5-2.5 part, benzalkonium bromide solution 2-2.5 part, dimethyl sulfoxide 2.5-10 part, cetostearyl alcohol 6-50 part; Purified water 25-150 part; ; Containing carbazochrome sodium sulfonate 40-80mg in ointment described in every 10g;
According to described number, mix to obtain aqueous phase by glycerol, sodium lauryl sulphate, ethyl hydroxybenzoate, dimethyl sulfoxide, purified water, benzalkonium bromide solution and high-purity carbazochrome sodium sulfonate 100 DEG C; In proportion cetostearyl alcohol, glyceryl monostearate and white vaseline are mixed to obtain oil phase at 90-95 DEG C; After aqueous phase and oil phase emulsifying, homogenizing, cooling, embedding and get final product.
9. the method for a kind of carbazochrome sodium sulfonate semi-solid preparation of preparation according to claim 7, is characterized in that,
The method preparing described gel comprises: the medicinal substrate Ingredient Amount of 1 part of composite use of high-purity carbazochrome sodium sulfonate is respectively: viscosity be 934 carbomer 1-5 part, triethanolamine 0.1-2.5 part, glycerol 2.5-25 part, ethyl hydroxybenzoate 0.1-0.25 part, purified water 25-150 part; Containing carbazochrome sodium sulfonate 40-80mg in gel described in every 5g;
According to described number, get viscosity be 934 carbomer to be evenly spread on purified water surface fully swelling, then add triethanolamine and stir, adjust ph is 5 ~ 6, obtains substrate; Get the high-purity carbazochrome sodium sulfonate of proportional quantity, glycerol, ethyl hydroxybenzoate mixing, add gradually in the substrate under stirring, then after adding purified water mixing, embedding and get final product.
10. a kind of carbazochrome sodium sulfonate semi-solid preparation of preparation according to claim 1, is characterized in that, the high-purity carbazochrome sodium sulfonate of purity more than 99.80%, and its preparation method comprises the following steps:
Step 1, in the reaction vessel that mechanical agitator is housed, add sodium sulfite 20.8g and deionized water 100mL, with the speed stirring and dissolving of 70.0 ~ 80.0r/min, add Adenaron 23.6 parts again, control reactant liquor at 15.0 ~ 25.0 DEG C with the speed stirring reaction of 50.0 ~ 60.0r/min, after having orange/yellow solid to separate out, continue stirring 3 ~ 5 hours, filter, precipitate to obtain carbazochrome sodium sulfonate crude product;
Step 2, the deionized water adding gained carbazochrome sodium sulfonate crude product and 10.0 ~ 15.0 times of quality in churned mechanically reaction bulb is being housed, stir with the speed of 50.0 ~ 60.0r/min and be heated to solvent refluxing, after dissolution of solid, addition active carbon 1.0 parts, continues stirring and refluxing 30 ~ 60 minutes, filtered while hot, filtrate is slowly reduced to room temperature crystallize 30-35 minute, filter, drying under reduced pressure 4-6 hour at being deposited in 60.0 DEG C, obtains high-purity carbazochrome sodium sulfonate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410688237.3A CN104473864B (en) | 2014-11-25 | 2014-11-25 | Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410688237.3A CN104473864B (en) | 2014-11-25 | 2014-11-25 | Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104473864A true CN104473864A (en) | 2015-04-01 |
| CN104473864B CN104473864B (en) | 2017-02-22 |
Family
ID=52748570
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410688237.3A Active CN104473864B (en) | 2014-11-25 | 2014-11-25 | Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104473864B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382818A (en) * | 2017-08-03 | 2017-11-24 | 江苏汉斯通药业有限公司 | A kind of synthetic method of high cleanliness Carbazochrome Sodium Sulfonate |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA002967B1 (en) * | 1998-04-21 | 2002-12-26 | Тейдзин Лимитед | Medical compositions for application to mucosa |
| CN1562001A (en) * | 2004-03-29 | 2005-01-12 | 南昌弘益科技有限公司 | Carbazochrome sodium sulfoate dripping pill and its preparing method |
| CN101554377A (en) * | 2008-04-09 | 2009-10-14 | 鲁南制药集团股份有限公司 | Pharmaceutical composition containing prasugrel and carbazochrome sodium sulfonate |
| CN102018675A (en) * | 2009-11-11 | 2011-04-20 | 海南利能康泰制药有限公司 | Carbazochrome sodium sulfonate freeze-dried powder injection and preparation method thereof |
| CN102125559A (en) * | 2010-01-17 | 2011-07-20 | 鲁南制药集团股份有限公司 | Pharmaceutical composition containing pentoxifylline and carbazochrome sodium sulfonate and application thereof |
| CN102757378A (en) * | 2012-07-06 | 2012-10-31 | 江苏汉斯通药业有限公司 | Preparation method of carbazochrome sodium sulfonate |
-
2014
- 2014-11-25 CN CN201410688237.3A patent/CN104473864B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA002967B1 (en) * | 1998-04-21 | 2002-12-26 | Тейдзин Лимитед | Medical compositions for application to mucosa |
| CN1562001A (en) * | 2004-03-29 | 2005-01-12 | 南昌弘益科技有限公司 | Carbazochrome sodium sulfoate dripping pill and its preparing method |
| CN101554377A (en) * | 2008-04-09 | 2009-10-14 | 鲁南制药集团股份有限公司 | Pharmaceutical composition containing prasugrel and carbazochrome sodium sulfonate |
| CN102018675A (en) * | 2009-11-11 | 2011-04-20 | 海南利能康泰制药有限公司 | Carbazochrome sodium sulfonate freeze-dried powder injection and preparation method thereof |
| CN102125559A (en) * | 2010-01-17 | 2011-07-20 | 鲁南制药集团股份有限公司 | Pharmaceutical composition containing pentoxifylline and carbazochrome sodium sulfonate and application thereof |
| CN102757378A (en) * | 2012-07-06 | 2012-10-31 | 江苏汉斯通药业有限公司 | Preparation method of carbazochrome sodium sulfonate |
Non-Patent Citations (1)
| Title |
|---|
| 聂延君等: ""卡络磺钠片的处方工艺研究"", 《中国药业》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382818A (en) * | 2017-08-03 | 2017-11-24 | 江苏汉斯通药业有限公司 | A kind of synthetic method of high cleanliness Carbazochrome Sodium Sulfonate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104473864B (en) | 2017-02-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102134226B (en) | Phenyl C-glucoside derivatives, preparation method and use thereof | |
| CN100545164C (en) | The preparation technology of disodium cantharidinate | |
| CN103880910A (en) | Preparation method and application of cycloastragenol | |
| CN107714642A (en) | A kind of oral solution of EV71 viruses and CVA16 viral inhibitors and preparation method thereof | |
| CN101935334A (en) | Berberine glycyrrhetinic acid enantiomeric salts and preparation method and application thereof | |
| KR20090037435A (en) | Tablet composition containing chinese herb extract | |
| CN105209439A (en) | Process for manufacture of gadofosveset trisodium monohydrate | |
| KR20190010578A (en) | New Dapagliflozoline Crystal Forms and Methods of Making and Uses Thereof | |
| CN104473864A (en) | Carbazochrome sodium sulfonate semisolid preparation and preparation method thereof | |
| JP2002543125A (en) | Compositions of boswellic acid from Boswellia serrata rubber resin for the treatment of lymphoproliferative and autoimmune conditions | |
| CN104490762A (en) | Tranexamic acid external semisolid preparation and preparation method thereof | |
| CN103040849A (en) | Tannic acid preparation for treating burn, bedsore and diaper dermatitis and preparation method thereof | |
| CN102250066B (en) | Fasudil derivative and preparation method thereof | |
| JP7250920B2 (en) | Pharmaceutical composition containing ilaprazole or its salt and method for preparing the same | |
| CN113952324A (en) | Application of salvianic acid A-ester in preparation of medicine for treating cerebral arterial thrombosis, pharmaceutical composition and preparation method of salvianic acid A-ester | |
| TWI599571B (en) | Process for prepararing intermediate compound of ixazomib citrate, and ixazomib citrate made thereby | |
| CN100427068C (en) | Kangai drip pill for treating tumour, hepatitis B and its preparation method | |
| CN100375630C (en) | Compound drop pills with flavescent sophora root and its preparation method | |
| CN100364505C (en) | Fengshining drop pill for treating rheumatism and its preparation method | |
| CN100358506C (en) | Compound musk drip pill and its preparation method | |
| CN1332669C (en) | Dripping pills for reducing swelling and easing pain and its preparing method | |
| CN1315472C (en) | Motherwort dropping pill and its preparing method | |
| CN100358500C (en) | Fleabane and earthworm dripping pill and its preparing method | |
| CN115778896B (en) | Tranexamic acid injection and its preparation method and use | |
| CN1315464C (en) | Wild aconite drip pill for treating cancer pain and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170323 Address after: Meilan District 570100 in Hainan province Haikou city Guilin Yang Development Zone (Guilin ocean power station on the right side) Patentee after: Hainan Yi Shun Pharmaceutical Co., Ltd. Address before: 570208 Hainan province Haikou Haidian road two Binjiang coast 4~1701 Patentee before: Chen Changtan |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170605 Address after: 550000 Guizhou city of Guiyang province Zhazuo Xiuwen County Medical Industrial Park, Wanjiang Road Patentee after: Guizhou Jian Ruian Pharmaceutical Co., Ltd. Address before: Meilan District 570100 in Hainan province Haikou city Guilin Yang Development Zone (Guilin ocean power station on the right side) Patentee before: Hainan Yi Shun Pharmaceutical Co., Ltd. |