CN101732241A - Cream of butenafine hydrochloride and preparation method thereof - Google Patents
Cream of butenafine hydrochloride and preparation method thereof Download PDFInfo
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- CN101732241A CN101732241A CN200910215162A CN200910215162A CN101732241A CN 101732241 A CN101732241 A CN 101732241A CN 200910215162 A CN200910215162 A CN 200910215162A CN 200910215162 A CN200910215162 A CN 200910215162A CN 101732241 A CN101732241 A CN 101732241A
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- butenafine hydrochloride
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Abstract
The invention belongs to the field of medicine preparations, which in particular relates to butenafine hydrochloride cream and a preparation method thereof. In order to lower the adverse reaction of the traditional butenafine hydrochloride cream and further enhance the curative effect of a medicine, the invention provides the cream containing butenafine hydrochloride and the preparation method thereof. The cream provided by the invention comprises two parts of butenafine hydrochloride liposome and a cream substrate. The preparation method of the cream comprises the following steps: firstly, preparing the butenafine hydrochloride liposome, then preparing the cream substrate, afterwards adding butenafine hydrochloride liposome suspension into the cream substrate according to the preset concentration, stirring evenly and subpackaging so as to obtain the cream.
Description
Technical field
The invention belongs to field of medicine preparations, be specifically related to ointment of a kind of butenafine hydrochloride and preparation method thereof.
Background technology
Shallow epidermis skin fungal infectious disease occupies very high ratio in dermatosis, general easy recurrence is healed than refractory, belongs to one of refractory skin.The common skin fungal infectious disease comprises the tinea manuum, tinea pedis, tinea cruris, tinea corporis, tinea capitis etc. clinically.Its symptom mainly shows local skin moist flushing, erosion, dipping turns white or play phlysis, skin pruritus unbearably, scratch after often because of secondary infection causes erysipelas and lymphangitis etc., dry back easily the keratinization desquamation, chap.What cause cutaneous fungal infection mainly contains trichophyton, alpha fungus, trichophyton gypseum, Trichophyton violaceum, chaff shape fish-scale tinea bacterium, ascospore bacterium, acrothesium floccosum, Candida albicans, Sabouraudites lanosus, Microsporum ferrugineum and Trichophyton verrucosum etc.
The drug main for the treatment of cutaneous fungal infection at present clinically will comprise imidazoles, triazole type, squalene epoxidase inhibitor and polyenoid class.The external antifungal agent relates generally to the external emulsifiable paste or the cream of clotrimazole, miconazole, ketoconazole, terbinafine, ciclopirox olamine and butenafine etc.
Butenafine hydrochloride can suppress fungus Squalene Cycloxygenase activity when low concentration, cause in the fungoid that Squalene gathers and ergosterol is synthetic not enough.Squalene has direct toxic action to the fungal cell, and it is dead fast to cause fungus; And ergosterol to be the fungal cell film formed essential composition, the synthetic deficiency of ergosterol is suppressed conk.This dual function of butenafine hydrochloride causes breaking of fungal cell membrane, shows powerful Fungicidally active.This medicine also has direct destruction to fungal cell membrane when higher concentration.Different with imidazoles is that butenafine hydrochloride does not suppress cytochrome P 450 enzymes, does not influence adrenal gland and sex gland hormones and synthesizes.
Application for a patent for invention prospectus CN 1727325A discloses ointment of a kind of butenafine hydrochloride and preparation method thereof (referring to the 3rd section of Instructions Page 2), specifically adopts following prescription (percentage by weight): butenafine hydrochloride 0.08-0.1%, stearic acid 9-12%, white vaseline 7-10%, glyceryl monostearate 4.5-7%, polysorbate65-75%, propylene glycol 4-8%, methylcellulose 0.04-0.07%, ethyl hydroxybenzoate 0.01-0.02%, distilled water are an amount of.Disclosed preparation technology is: stearic acid, white vaseline and glyceryl monostearate are contained in container, 70-80 ℃ of heat fused, as oil phase; Again Tween-80, propylene glycol, ethyl hydroxybenzoate and butenafine hydrochloride adding are dissolved with in the distilled water of methylcellulose, are heated to 70-80 ℃, as water; Water is under agitation joined in the oil phase, constantly stir, form emulsion bases type ointment, be sub-packed in the emulsifiable paste that promptly gets hydrochloric butenafine in the pipe until cooling off.But do not provide any pharmacodynamics data that this ointment is treated shallow epidermis skin fungal infection.
The weight percentage of butenafine hydrochloride is generally 1% in the butenafine hydrochloride ointment of Shi Yonging clinically.The ointment of existing butenafine hydrochloride all has following common adverse reactions: local excitation, erythema, pruritus, burning sensation, sensation of pricking, contact dermatitis etc.
And the key for the treatment of skin disease success to be medicine must see through horny layer reach diseased region, and keep certain hour.Liposome, is compared with other dosage forms owing to have similar structure to the physiology film as the carrier of percutaneous drug delivery, can make medicine have bigger keratodermatitis transit dose, avoids not good enough because of penetrating the curative effect that the dose deficiency causes; Simultaneously medicine seldom enters blood circulation, has therefore reduced the serious toxic and side effects of some medicines due to when using general formulation.In addition, liposome is biodegradable, and avirulence own does not produce skin irritation yet, is the ideal carrier of local skin administration.
Summary of the invention
In order to reduce the untoward reaction of existing butenafine hydrochloride ointment, further improve curative effect of medication, the invention provides a kind of ointment that contains butenafine hydrochloride and preparation method thereof.Ointment provided by the invention is made up of butenafine hydrochloride liposome and emulsifiable paste matrix two parts, its preparation method is for being prepared as butenafine hydrochloride the liposome of butenafine hydrochloride earlier, the refabrication emulsifiable paste matrix, according to predetermined concentration the butenafine hydrochloride liposome turbid liquor is added in the emulsifiable paste matrix then, stir, packing promptly.
Butenafine hydrochloride is encapsulated in the liposome, can significantly improves the Transdermal absorption effect of butenafine hydrochloride, improved the stability of butenafine hydrochloride simultaneously.The lipid bilayer of liposome and biomembrane have bigger similarity, and have and histocompatibility, are easy to the absorption of skin histology, have therefore promoted the Transdermal absorption of butenafine hydrochloride, have improved curative effect of medication, and have reduced toxic and side effects.
Can use various types of liposomees to seal butenafine hydrochloride in the present invention.The encapsulating material of butenafine hydrochloride liposome comprises film material and antioxidant, wherein said film material can be selected from phosphatidylcholine, soybean phospholipid, cephalin, lecithin, cholesterol and stearmide any one or multiple; Antioxidant is vitamin E.Preferably, described film material is made up of lecithin, cholesterol and stearmide;
In the present invention, the film material of preparation liposome and antioxidant according to the proportioning of weight portion are:
Lecithin 70-90
Cholesterol 5-25
Stearmide 0.5-5
Vitamin E 0.3-2
Preferably, above-mentioned film material and antioxidant according to the proportioning of weight portion are: lecithin: cholesterol: stearmide: vitamin E=80: 20: 1: 1.
The butenafine hydrochloride liposome of the present invention preparation mixed with emulsifiable paste matrix can prepare butenafine hydrochloride ointment of the present invention.Emulsifiable paste matrix of the present invention comprises the component of following portions by weight:
Excipient 200-300
Emulsifying agent 10-30
Stabilizing agent 5-25
Antiseptic 0.5-1
Above-mentioned excipient is selected from one or more in glycerol, liquid paraffin, stearic acid, glyceryl monostearate, octadecanol, white vaseline and the lanoline; Preferably, described excipient is glycerol, glyceryl monostearate and white vaseline.
The aforementioned stable agent is selected from one or more in mannitol, sucrose, beta-schardinger dextrin-, Dextran 40, trehalose and the ethyl lactate; Preferably, described stabilizing agent is made up of Dextran 40 and ethyl lactate.
Foregoing preservatives is selected from one or more in benzalkonium bromide, chlorhexidine acetate, methyl parahydroxybenzoate, ethylparaben and the propyl p-hydroxybenzoate; Preferably, described antiseptic is an ethylparaben.
Mentioned emulsifier is selected from one or more in polysorbate 20, polysorbate 60, polyoxyethylene sorbitan monoleate, sorbester p17 or dodecyl sodium sulfate and the sodium hexadecyl sulfate, and preferably, described emulsifying agent is a polyoxyethylene sorbitan monoleate.Polyoxyethylene sorbitan monoleate can obviously improve the stability of butenafine hydrochloride liposome, and polyoxyethylene sorbitan monoleate is a 2.0-5.0% (polyoxyethylene sorbitan monoleate: emulsifiable paste matrix) to the protection concentration of liposome.
In the present invention, emulsifying agent not only can play the effect of adjusting product viscosity and emulsifying effectiveness, make originally can not be compatible oil phase and the effect of water by emulsifying agent form uniform dosage form, more liposome is played stable effect, reduce the leakage of butenafine hydrochloride in the liposome, improve the stability of butenafine hydrochloride liposome.
Correspondingly, the invention provides a kind of preparation method of butenafine hydrochloride emulsifiable paste.Concrete steps are as follows:
(1) preparation butenafine hydrochloride liposome.Concrete grammar is: earlier a certain proportion of film material and antioxidant that is dissolved in dichloromethane is rotated evaporation, the butenafine hydrochloride that adds predetermined concentration behind the evaporate to dryness organic solvent is proceeded rotation, the liposome suspension of butenafine hydrochloride has been sealed in formation, behind the ultra-sonic dispersion, through gel filtration, fraction collection makes the butenafine hydrochloride liposome liquid.In the butenafine hydrochloride liposome of the present invention's preparation, the envelop rate of the butenafine hydrochloride liposome of preparation is not less than 80%.
(2) preparation emulsifiable paste matrix.Concrete grammar is: according to the prescription of emulsifiable paste matrix, excipient, emulsifying agent as oil phase, as water, are melted stabilizing agent, antiseptic, distilled water respectively or dissolving, sterilization or degerming are mixed and made into emulsifiable paste matrix with oil phase and water again behind the mixing.
(3) according to predetermined concentration the butenafine hydrochloride liposome solutions is added in the emulsifiable paste matrix, the volume of butenafine hydrochloride liposome solutions (ml) is 1 with the ratio of the weight (g) of emulsifiable paste matrix: 4-19, stir and carry out packing, can make butenafine hydrochloride emulsifiable paste of the present invention.
In a word, butenafine hydrochloride emulsifiable paste provided by the invention compared with prior art has following advantage:
(1) improved the curative effect of medicine.The present invention is by the pharmacodynamic study of embodiment 8 butenafine hydrochloride emulsifiable pastes, the result shows that butenafine hydrochloride emulsifiable paste provided by the invention is compared with the usual cream that prior art provides has significant difference (p＜0.05) aspect the total effective rate of treatment tinea pedis.Therefore, butenafine hydrochloride emulsifiable paste provided by the invention has the high characteristics of cure rate aspect the tinea pedis that causes of treatment superficial fungous infection of skin.
(2) significantly reduce toxic and side effects, to skin nonirritant almost.The present invention is by the pharmacodynamic study of embodiment 8 butenafine hydrochloride emulsifiable pastes, the result shows that butenafine hydrochloride emulsifiable paste provided by the invention is compared with the usual cream that prior art provides has significant difference (p＜0.05) aspect the untoward reaction that causes in the treatment tinea pedis.Therefore, butenafine hydrochloride emulsifiable paste provided by the invention obviously reduces in toxic and side effects aspect the tinea pedis that causes of treatment superficial fungous infection of skin.
The specific embodiment
Below further describe the present invention by the specific embodiment, the present invention is not limited only to following examples.
First: pharmaceutical preparation part
Embodiment 1 butenafine hydrochloride emulsifiable paste
(1) preparation of butenafine hydrochloride liposome and checking
1. the preparation of butenafine hydrochloride liposome
Butenafine hydrochloride 10.00g
Ethanol is an amount of
Lecithin 16.02g
Cholesterol 4.04g
Stearmide 0.20g
Vitamin E 0.20g
Preparation technology:
(1) butenafine hydrochloride is dissolved in the adequate amount of ethanol;
(2) take by weighing lecithin, cholesterol, stearmide and the vitamin E of recipe quantity;
(3) with dichloromethane load weighted each film material component is fully dissolved in the ball-type bottle after, add dichloromethane to 100ml, on Rotary Evaporators, 40 ℃ of 100rpm rotary evaporation that reduces pressure, after treating the complete evaporate to dryness of organic solvent, add the butenafine hydrochloride alcoholic solution 25ml for preparing and continue rotary evaporation, thereby the lipid film on the bottle wall is peeled off, collect the liposome suspension then;
(4) suspension of collecting is carried out ultra-sonic dispersion with bath formula Ultrasound Instrument;
(5) will filter by solvent resistant column through the butenafine hydrochloride liposome liquid of ultra-sonic dispersion, collect first eluting peak liquid 20ml, be the butenafine hydrochloride liposome liquid;
(6) will cross butenafine hydrochloride liposome liquid behind the post through the filter membrane aseptic filtration of 0.22 μ m, filtered solution calibrating back is standby.
2. the mensuration of butenafine hydrochloride liposome encapsulation.
2.1 instrument
RE-524 type Rotary Evaporators (the inferior Rong Shenghua in Shanghai); KT-300Y type ultrasound wave medicine processor (hat ultrasound wave Co., Ltd in Jining); XSZ-109 optical microscope (Guangzhou instrument plant); 752C ultraviolet-uisible spectrophotometer (Shanghai the 3rd instrument plant).
2.2 entrapment efficiency determination
(1) preparation of standard curve
Precision takes by weighing butenafine hydrochloride standard substance 50mg, adds the dehydrated alcohol minimal amounts of dissolved and is settled to 10ml as dense liquid storage.Precision is measured the dense liquid storage of 0.2ml and add phosphate buffer to scale in the measuring bottle of 25ml, is measuring 0.5,1.0 respectively, 1.5,2.0,2.5ml is in the 10ml measuring bottle, being settled to scale with phosphate buffer, is the blank trap of surveying in the 282nm place with the phosphate buffer.Trying to achieve regression equation is A=0.0098+0.0293c, r=0.9998 (n=5), and promptly butenafine hydrochloride is at 2～10mgL
-1It is linear that scope is.
(2) mensuration of sample envelop rate
Precision is measured the 4ml liposome, adds phosphate buffer and is diluted to 20ml, and in the bag filter of packing into, the phosphate buffer that places 50ml is changed a dialysis solution in 4 ℃ of dialysis down every 12h, changes altogether 3 times.Collect dialysis solution and be settled to 250ml, survey trap at λ=282nm, the substitution regression equation promptly gets concentration c.It is W that concentration conversion is become quality
TripAccording to ER%=(W
Always-W
Trip)/W
Always* 100% computational envelope rate, wherein W
Always, W
TripThe free drug amount of representing dosage respectively and not wrapping into.
2.3 optical microscope is seen
The liposome that takes a morsel dilutes with buffer, drips to microscope slide in 40 * 16 times of mirrors to observe down, and particle diameter homogeneous quality more is good more, and free crystal is few more good more.
2.4 result of the test
Specifically see Table 1.
Table 1 butenafine hydrochloride liposome encapsulation and Jing Guan
As can be seen from the table, envelop rate is all above 80%.
(2) preparation of emulsifiable paste matrix
Composition weight/g
Excipient glycerol 50
Glyceryl monostearate 150
White vaseline 100
Emulsifying agent polyoxyethylene sorbitan monoleate 20
Stabilizing agent Dextran 40 5
Ethyl lactate 10
Antiseptic ethylparaben 5
Water adds to 1000
Preparation technology:
(1) by the accurate weighing glycerol of above weight proportion, glyceryl monostearate, white vaseline, polyoxyethylene sorbitan monoleate, Dextran 40, ethyl lactate, ethylparaben.
(2) glyceryl monostearate, white vaseline are heated in water-bath dissolve, add polyoxyethylene sorbitan monoleate, glycerol again and be heated to 80 ℃, form oil phase;
(3) add Dextran 40, ethyl lactate, the ethylparaben of recipe quantity, adding distil water is to 1000g, and is heated to 80 ℃, forms water;
(4) the slow stream of oil phase is added to aqueous phase, the limit edged stirs, until condensation, check emulsifiable paste matrix.
(3), butenafine hydrochloride emulsifiable paste preparation
Get butenafine hydrochloride liposome solutions 5ml, stir, and carry out packing, can make butenafine hydrochloride emulsifiable paste of the present invention with the 95g emulsifiable paste matrix.
Embodiment 2-7 butenafine hydrochloride emulsifiable paste and preparation thereof
(1) butenafine hydrochloride liposome
For the convenience of narrating, following use table 2 is described the composition of embodiment 2-7 butenafine hydrochloride liposome prescription.
Table 2 embodiment 2-7 butenafine hydrochloride liposome prescription
Preparation technology: the preparation technology of embodiment 2-7 (being routine 2-7) butenafine hydrochloride liposome is with embodiment 1.
(2) emulsifiable paste matrix
For the convenience of narrating, following use table 3 is described the composition of embodiment 2-7 emulsifiable paste matrix prescription.
Table 3 embodiment 2-7 emulsifiable paste matrix prescription
Preparation technology: the preparation technology of embodiment 2-7 (being routine 2-7) emulsifiable paste matrix is with embodiment 1.
(3), butenafine hydrochloride emulsifiable paste preparation
According to predetermined concentration the butenafine hydrochloride liposome solutions is added in the emulsifiable paste matrix, the volume of butenafine hydrochloride liposome solutions (ml) is 1 with the ratio of the weight (g) of emulsifiable paste matrix: 4-19, stir and carry out packing, can make butenafine hydrochloride emulsifiable paste of the present invention.Specifically see Table 4.
The composition of table 4 embodiment 2-7 butenafine hydrochloride emulsifiable paste
Preparation technology: the preparation technology of embodiment 2-7 (being routine 2-7) butenafine hydrochloride emulsifiable paste is with embodiment 1.
Second portion: butenafine hydrochloride pharmacodynamics part
Embodiment 8 butenafine hydrochloride emulsifiable pastes are to tinea pedis patient clinical observation on the therapeutic effect
1. clinical manifestation
Tinea pedis (claiming beriberi again) is a common clinical, how to cause, and infection rate is high once more by superficial fungous infection of skin, especially with summer and autumn pilosity be characteristics.Though tinea pedis does not have the melancholy of life, also normal really puzzlement people's life, and the trend that rises is year by year arranged.Medically usually beriberi is divided three types: erosive type, vesicle type, keratinization type tinea pedis.Its basic clinical manifestation is: local skin humidity, flushing, erosion, dipping turn white or play phlysis, skin pruritus unbearably, dry back easily the keratinization desquamation, chap etc.And described infection is can be contagious, and may recur.
2. clinical data
This organizes 200 examples, male 120 examples, and women 80 examples, in age 11-50 year, the course of disease 2 did not wait in thoughtful 3 years.One of following situation person is not by selected: external corticosteroid hormone and antifungal drug therapist in (1) treatment the last fortnight; (2) system applies Corticosterone hormone and antifungal drug therapist in the previous moon of treatment; (3) diabetes or suffer from other serious immune dysfunction person are arranged; (4) person that mismatches this therapeutic scheme.
3. method
3.1 grouping and administration:
Emulsifiable paste A group: administration 1% butenafine hydrochloride emulsifiable paste (preparation technology is with CN 1727325A example two);
Emulsifiable paste B group: administration 1% butenafine hydrochloride emulsifiable paste (according to the butenafine hydrochloride emulsifiable paste of the embodiment of the invention 1 preparation, 1%);
More than all medicines be applied to the affected part, every day 2 times, logotype 14 days.
3.2 untoward reaction emergency processing
If after using this product, the state of an illness person of increasing the weight of or other skin lesion severe patients such as local excitation, erythema, pruritus, burning sensation, sensation of pricking, contact dermatitis occur discontinues medication immediately and seeks medical advice, and slighter symptom does not influence and continues treatment.
3.3 tracing observation
All patients are carried out tracing observation, and in time feedback helps the information of this programme.
4. interpretation of result
4.1 standard
4.1.1 recovery from illness: use to be subjected to the reagent thing after 7 days, stop pruritus, the skin lesion transference cure, not recurring within 14 days is to fully recover;
4.1.2 effectively: use to be subjected to the reagent thing after 7 days, stop pruritus, the skin lesion remission is not recurred within 7 days for effectively.
4.1.3 invalid: use to be subjected to the reagent thing after 7 days, pruritus alleviates to some extent, and the skin lesion symptom continues, and recurrence is arranged for invalid within 3 days.
4.2 date processing
4.2.1 write down recovery from illness number, total effectively number, the invalid number of each treatment group case respectively and cause the number of untoward reaction.
4.2.2 calculate total effective rate, inefficiency and untoward reaction rate respectively, and applied statistics software SPSS 11.0 carries out the χ of each treatment group total effective rate
2Check.If χ
2＞χ
2 0.05, 1=3.84 has significant difference with p＜0.05.Each treatment group group difference relatively.On onset time, relatively each treatment group group difference use t check.
4.3 result
Clinical effectiveness shows (specifically seeing Table 5):
Aspect the total effective rate and untoward reaction rate of treatment tinea pedis, butenafine emulsifiable paste B group is compared with A all has significant difference (p＜0.05).This shows, butenafine hydrochloride emulsifiable paste provided by the invention has cure rate height, characteristics that toxic and side effects is low aspect the tinea pedis that causes of treatment superficial fungous infection of skin, this illustrates that butenafine hydrochloride ointment provided by the invention compares the usual cream agent and improved curative effect of medication and reduced side effect.
Table 5 butenafine hydrochloride emulsifiable paste is to tinea pedis patient's curative effect
Annotate:
■Compare p＜0.05 with butenafine emulsifiable paste A group;
★Compare p＜0.05 with butenafine emulsifiable paste A group.
Owing to described the present invention according to above preferred embodiment, any to be equal to replacement all be conspicuous for the person of ordinary skill of the art, and be included among the present invention.
Claims (9)
1. ointment that contains butenafine hydrochloride is characterized in that it is made up of butenafine hydrochloride, liposome membrane material, antioxidant and emulsifiable paste matrix, wherein,
Described liposome membrane material is selected from one or more of phosphatidylcholine, soybean phospholipid, cephalin, lecithin, cholesterol and stearmide;
Described antioxidant is vitamin E;
Described emulsifiable paste matrix comprises excipient, emulsifying agent, stabilizing agent and antiseptic, wherein excipient is selected from one or more in glycerol, liquid paraffin, stearic acid, glyceryl monostearate, octadecanol, white vaseline and the lanoline, stabilizing agent is selected from one or more in mannitol, sucrose, beta-schardinger dextrin-, Dextran 40, trehalose and the ethyl lactate, and antiseptic is selected from one or more in benzalkonium bromide, chlorhexidine acetate, methyl parahydroxybenzoate, ethylparaben and the propyl p-hydroxybenzoate; Described emulsifying agent is selected from one or more in polysorbate 20, polysorbate 60, polyoxyethylene sorbitan monoleate, sorbester p17, dodecyl sodium sulfate and the sodium hexadecyl sulfate.
2. ointment as claimed in claim 1 is characterized in that described film material is made up of lecithin, cholesterol and stearmide.
3. ointment as claimed in claim 2 is characterized in that preparing the film material of liposome and vitamin E and according to the proportioning of weight portion is:
Lecithin 70-90
Cholesterol 5-25
Stearmide 0.5-5
Vitamin E 0.3-2.
4. ointment as claimed in claim 3 is characterized in that described film material and vitamin E according to the proportioning of weight portion are:
Lecithin 80
Cholesterol 20
Stearmide 1
Vitamin E 1.
5. ointment as claimed in claim 1 is characterized in that described excipient is glycerol, glyceryl monostearate and white vaseline.
6. ointment as claimed in claim 1 is characterized in that described stabilizing agent is made up of Dextran 40 and ethyl lactate.
7. ointment as claimed in claim 1 is characterized in that described antiseptic is an ethylparaben.
8. ointment as claimed in claim 1 is characterized in that described emulsifying agent is a polyoxyethylene sorbitan monoleate.
9. preparation method that contains the butenafine hydrochloride emulsifiable paste, it is characterized in that it is made up of following steps: preparation butenafine hydrochloride liposome earlier, the refabrication emulsifiable paste matrix, at last the butenafine hydrochloride liposome solutions is added in the emulsifiable paste matrix, the volume of butenafine hydrochloride liposome solutions is 1 with the ratio of the weight of emulsifiable paste matrix: 4-19 stirs promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910215162A CN101732241A (en) | 2009-12-26 | 2009-12-26 | Cream of butenafine hydrochloride and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910215162A CN101732241A (en) | 2009-12-26 | 2009-12-26 | Cream of butenafine hydrochloride and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103405781A (en) * | 2013-08-26 | 2013-11-27 | 江苏圣宝罗药业有限公司 | Pharmaceutical composition of compound clindamycin and tazarotene lipid complex |
| CN107115329A (en) * | 2017-04-28 | 2017-09-01 | 中国人民解放军第二军医大学第二附属医院 | A kind of compound Butenafine preparation and its application |
| CN110974780A (en) * | 2019-12-26 | 2020-04-10 | 普洱学院 | Bee pupa cream with antioxidant effect |
-
2009
- 2009-12-26 CN CN200910215162A patent/CN101732241A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103405781A (en) * | 2013-08-26 | 2013-11-27 | 江苏圣宝罗药业有限公司 | Pharmaceutical composition of compound clindamycin and tazarotene lipid complex |
| CN107115329A (en) * | 2017-04-28 | 2017-09-01 | 中国人民解放军第二军医大学第二附属医院 | A kind of compound Butenafine preparation and its application |
| CN110974780A (en) * | 2019-12-26 | 2020-04-10 | 普洱学院 | Bee pupa cream with antioxidant effect |
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Assignee: Lunan Beite Pharmaceutical Co., Ltd. Assignor: Lunan Pharmaceutical Group Co., Ltd. Contract record no.: 2010370000512 Denomination of invention: Cream of butenafine hydrochloride and preparation method thereof License type: Exclusive License Open date: 20100616 Record date: 20100909 |
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Inventor after: Zhao Zhiquan Inventor after: Zhang Zeping Inventor before: Zhao Zhiquan |
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Free format text: CORRECT: INVENTOR; FROM: ZHAO ZHIQUAN TO: ZHAO ZHIQUAN ZHANG ZEPING |
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Assignee: Lunan Beite Pharmaceutical Co., Ltd. Assignor: Lunan Pharmaceutical Group Co., Ltd. Contract record no.: 2010370000512 Date of cancellation: 20131016 |
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Application publication date: 20100616 |