CN103877117A - Hydrocortisone butyrate and zinc oxide medicine composition - Google Patents
Hydrocortisone butyrate and zinc oxide medicine composition Download PDFInfo
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- CN103877117A CN103877117A CN201410086364.6A CN201410086364A CN103877117A CN 103877117 A CN103877117 A CN 103877117A CN 201410086364 A CN201410086364 A CN 201410086364A CN 103877117 A CN103877117 A CN 103877117A
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Abstract
The invention relates to a steride cortical hormone medicine composition, and in particular to a medicine composition which takes hydrocortisone butyrate and zinc oxide as active ingredients.
Description
Technical field
The present invention relates to a kind of steroidal corticosteroid drug compositions, especially relate to a kind of pharmaceutical composition take hydrocortisone butyrate, zinc oxide as active component.
Background technology
Hydrocortisone butyrate (Hydrocortisone-17-butyrate, CAS:13609-67-1) be the one of steroidal 17-hydroxy-11-dehydrocorticosterone, can suppress the reaction of inflammation and allergic skin, also suppress to add related reaction of rapid regeneration and cause symptom with cell simultaneously, for example erythema, edema, thickization of skin, coarse the going down of skin surface, and alleviate the problems such as pruritus, burning sensation and pain.Owing to having introduced 17-butyrate on hydrocortisone molecule, make the fat-soluble better of hydrocortisone butyrate, thereby in the time of external curing, can reach better curative effect, retain the lighter advantage of side effect of hydrocortisone simultaneously, be a kind of can be for child's external steroidal 17-hydroxy-11-dehydrocorticosterone.
Zinc oxide (ZnO), as a kind of metal-oxide, the outer used time has convergence, sterilization.Promote wound healing, and absorb ultraviolet effect, be therefore used to prepare the pharmaceutical composition of external, existing zinc oxide external preparation mainly contains zinc ointment, the preparations such as compound cod-liver oil zinc ointment, and its zinc oxide content is not from 10-20% etc.
But because hydrocortisone butyrate has the compound of 11,17,21-trihydroxy-17 butyrate structure as one, its stability in preparation is received the direct impact of pH value.Test and find that the impurity producing in emulsion of hydrocortisone butyrate is mainly 21-hydrocortisone butyrate in storage process through us, the main cause that produces this impurity is that hydrolysis has occurred 17 ester groups in storage process, and similar ester exchange reaction occurs and become hydrocortisone-21-butyrate with 21 hydroxyls.Hydrocortisone-21-butyrate (HCB-21) that in the experiment of hydrocortisone butyrate preparation stability, main impurity ester exchange produces is also disclosed in U.S. Patent application US20040152682A1 description the second page table 3, so for example, in order to improve the general stability of the method guarantee hydrocortisone butyrate that pH value is accurately controlled in emulsifiable paste, the CN200910228788.0 of adopting of stability of preparation.
(horse military camp as everyone knows, the type of carboxyester hydrolysis and influence factor, " Xinyang Normal College's journal: natural science edition ", 11 4 phases of volume in 1998,417-421) tertiary alcohol ester hydrocortisone butyrate can be hydrolyzed under acidity or alkali condition, but because different pH values can produce larger impact to ester hydrolysis rate.So in order to protect better the stability of hydrocortisone butyrate, generally hydrocortisone butyrate is made to ointment or the oil phase in Water-In-Oil or oil-in-water emulsifiable paste.
Zinc oxide (ZnO), as a kind of metal-oxide, the outer used time has convergence, sterilization.Promote wound healing, and absorb ultraviolet effect, be therefore used to prepare the pharmaceutical composition of external, existing zinc oxide external preparation mainly contains zinc ointment, the preparations such as compound cod-liver oil zinc ointment, and its zinc oxide content is not from 10-20% etc.Simultaneous oxidation zinc can cause the significant change of preparation pH value, thereby promotes hydrocortisone butyrate to decompose.
Summary of the invention
In order to obtain better a kind of external used medicine for the treatment of inflammation, scientific research personnel, through constantly researching and developing hydrocortisone butyrate and zinc oxide are made to complex external medicine compositions, especially uses more separately hydrocortisone butyrate, zinc oxide curative effect to be all significantly improved for eczema.But in research and development, find that the content of hydrocortisone butyrate in accelerated test declines rapidly after zinc oxide, hydrocortisone butyrate simply mix.Generation estimation and the zinc oxide of this situation have produced catalytic action to the ester exchange of hydrocortisone butyrate.
For overcoming the problems of the prior art, the invention provides a kind of hydrocortisone butyrate, zinc oxide compound cream, by making oil-in-water unguentum, zinc oxide is placed in to oil reservoir, and creationary hydrocortisone butyrate is placed in water layer, strive avoiding the catalytic action of the ester exchange of zinc oxide to hydrocortisone butyrate.But surprisingly when the oil reservoir material that contains zinc oxide with contain hydrocortisone butyrate water layer mixing of materials time, there are tween 120 surfactants of HLB value even if adopt, also oil phase cannot be scattered in water.
Through constantly research and test, we ought add sodium lauryl sulphate and peregal A mixed surfactant at surprised discovery in the oil phase that contain zinc oxide, water can will be scattered in water by the oil phase that contains zinc oxide after adding surfactant better simultaneously.
A kind of pharmaceutical composition, is characterized in that containing active component hydrocortisone butyrate and zinc oxide.
A kind of pharmaceutical composition, is characterized in that being made up of active component hydrocortisone butyrate and zinc oxide, pharmaceutic adjuvant that one or more are applicable to Transdermal absorption.
Aforementioned pharmaceutical compositions, is characterized in that for externally-applied medicinal composition.The meaning of externally-applied medicinal composition is to directly act on skin, to the disease performance therapeutical effect of skin surface.
Above-mentioned compositions, the 0.01-0.1% that the content that it is characterized in that hydrocortisone butyrate is composition weight, above-mentioned compositions, the 1-5% that the content that it is characterized in that zinc oxide is composition weight.
Above-mentioned compositions, is characterized in that having the unguentum of oil-in-water structure.Above-mentioned compositions, is characterized in that zinc oxide is positioned at oil reservoir, and hydrocortisone butyrate is positioned at water layer.Above-mentioned compositions, it is characterized in that oil reservoir adjuvant contains as one or more compositions in oil phase substrate, the surfactant of pharmaceutically useful adjuvant, water layer adjuvant is made up of one or more and water in surfactant, wetting agent, PH regulator, antiseptic.Above-mentioned emulsifiable paste, is characterized in that described oil phase substrate is one or more in vaseline, paraffin, liquid paraffin, lanoline, Cera Flava, dimethicone, stearic acid, hexadecanol, octadecanol, vegetable oil; Surfactant is one or more of soap class, fatty alcohol sulfate or sodium class, higher fatty acids class, polyhydric alcohol esters, polyoxyethylene ether apoplexy due to endogenous wind; Wetting agent is one or more in glycerol, propylene glycol, sorbitol, and antiseptic is one or more in benzalkonium bromide, benzalkonium chloride, parabens antiseptic, benzoic acid, sodium benzoate, sorbic acid; PH adjusting agent is one or more in phosphate buffer salt, Tris buffer salt, citrate buffer salt.
Above-mentioned ointment, the compound method of described emulsifiable paste is as follows:
(1) oil phase preparation: zinc oxide is mixed with surfactant, and temperature remains on 70-90 ℃, then take in oil phase substrate heating and melting and become solution, after both mixing, temperature remains on 70-90 ℃;
(2) water preparation: hydrocortisone butyrate micropowder is dispersed in the wetting agent of solvent, will adds the water heating of pH value regulator, surfactant, antiseptic, the temperature that stirs remains on 70-90 ℃; Then be added to the water and stir, temperature remains on 70-90 ℃; (3) close phase: the oil phase of step (1) preparation is slowly added in the water of step (2) preparation, stir, maintain the temperature at 70-90 ℃, stir 10-30min, be cooled to cream.
The specific embodiment
Below will by embodiment, the invention will be further described, these descriptions are not that content of the present invention is further limited.One skilled in the art will understand that the replacement that is equal to that technical characterictic of the present invention is done, or improve accordingly, within still belonging to protection scope of the present invention.
The PAP that the emulsifiable paste that all embodiment make all props up with 10g/ divides and packages spare.Hydrocortisone butyrate used is the micropowder of particle size range 5-50 μ m, and the particle diameter of zinc oxide is at the micropowder of 5-10 μ m, and maximum particle diameter is less than 30 μ m.
pre-embodiment 1
Active component: hydrocortisone butyrate 1g, zinc oxide 10g
Oil-phase component: white vaseline 50g, octadecanol 30g, liquid paraffin 30g, surfactant 1
Water-phase component: surfactant 2, glycerol 50g, propylene glycol 20g, ethyl hydroxybenzoate 1g, citric acid (C
6h
8o
7h
2o) 10g, sodium citrate (Na
3c
6h
5o
72H
2o) 18g water for injection adds to 1000g
By above proportioning accurate weighing, emulsifiable paste process for preparation is as follows:
(1) oil phase preparation: zinc oxide is mixed in container with the oil-phase component that is heated to melting, and temperature remains on 90 ℃;
(2) water preparation: surfactant 2, citric acid and sodium citrate, ethyl hydroxybenzoate are dissolved in water for injection, hydrocortisone butyrate is dispersed in glycerol, propylene glycol, both mix, heating, the temperature that stirs remains on 90 ℃;
(3) close phase: the oil phase of step (1) preparation is slowly added in the water of step (2) preparation, stir, maintain the temperature at 80 ℃, stir 30min, be cooled to cream, obtain 1000g emulsifiable paste.
Can illustrate by above-mentioned preliminary experiment, when adding sodium lauryl sulphate and peregal A mixed surfactant in the oil phase that contains zinc oxide, water can make the sense of touch of preparation better after adding surfactant 2 peregal A simultaneously.The preparation method of following examples, comparative examples is all according to the method preparation of embodiment 1.
embodiment 1
Active component: hydrocortisone butyrate 1g, zinc oxide 10g
Oil-phase component: white vaseline 50g, octadecanol 30g, liquid paraffin 30g, peregal A-20 35g, sodium lauryl sulphate 5g
Water-phase component: peregal A-20 10g, glycerol 50g, propylene glycol 20g, ethyl hydroxybenzoate 1g, citric acid (C
6h
8o
7h
2o) 10g, sodium citrate (Na
3c
6h
5o
72H
2o) 18g water for injection adds to 1000g
By above proportioning accurate weighing, emulsifiable paste process for preparation is as follows:
(1) oil phase preparation: zinc oxide is mixed in container with the oil-phase component that is heated to melting, and temperature remains on 90 ℃;
(2) water preparation: peregal A-20, citric acid and sodium citrate, ethyl hydroxybenzoate are dissolved in water for injection, hydrocortisone butyrate is dispersed in glycerol, propylene glycol, both mix, heating, the temperature that stirs remains on 90 ℃;
(3) close phase: the oil phase of step (1) preparation is slowly added in the water of step (2) preparation, stir, maintain the temperature at 80 ℃, stir 30min, be cooled to cream, obtain 1000g emulsifiable paste.
embodiment 2
Active component: hydrocortisone butyrate 1g, zinc oxide 5g
Oil-phase component: white vaseline 50g, octadecanol 30g, liquid paraffin 30g, peregal A-20 35g, sodium lauryl sulphate 5g
Water-phase component: peregal A-20 10g, glycerol 50g, propylene glycol 20g, ethyl hydroxybenzoate 1g, citric acid (C
6h
8o
7h
2o) 10g, sodium citrate (Na
3c
6h
5o
72H
2o) 18g water for injection adds to 1000g
embodiment 3
Active component: hydrocortisone butyrate 0.1g, zinc oxide 5g
Oil-phase component: white vaseline 30g, octadecanol 100g, liquid paraffin 30g, peregal A-20 25g, sodium lauryl sulphate 5g
Water-phase component: peregal A-20 20g, glycerol 50g, propylene glycol 50g, methyl hydroxybenzoate 1g, citric acid (C
6h
8o
7h
2o) 7g water for injection adds to 1000g
embodiment 4
Active component: hydrocortisone butyrate 1g, zinc oxide 1g
Oil-phase component: white vaseline 30g, octadecanol 50g, liquid paraffin 70g, peregal A-20 30g, sodium lauryl sulphate 5g
Water-phase component: peregal A-20 10g, glycerol 10g, propylene glycol 50g, methyl hydroxybenzoate 1g, citric acid (C
6h
8o
7h
2o) 10g, sodium citrate (Na
3c
6h
5o
72H
2o) 18g water for injection adds to 1000g
comparative examples 1
Active component: see the following form
Oil-phase component: white vaseline 50g, octadecanol 30g, liquid paraffin 30g, peregal A-20 35g, sodium lauryl sulphate 5g
Water-phase component: peregal A-20 10g, glycerol 50g, propylene glycol 20g, ethyl hydroxybenzoate 1g, citric acid (C
6h
8o
7h
2o) 10g, sodium citrate (Na
3c
6h
5o
72H
2o) 18g water for injection adds to 1000g
| Group number | Hydrocortisone butyrate (g) | Zinc oxide (g) |
| 1-1 | 1 | ? |
| 1-2 | ? | 5 |
comparative examples 2
Principal agent: hydrocortisone butyrate 1g, zinc oxide 5g
Adjuvant: white vaseline 100g, octadecanol 30g, liquid paraffin 30g,
Peregal A-20 50g, glycerol 50g, propylene glycol 20g, ethyl hydroxybenzoate 1g, citric acid (C
6h
8o
7h
2o) 10g,
Sodium citrate (Na
3c
6h
5o
72H
2o) 18g water for injection adds to 1000g
By above proportioning accurate weighing, emulsifiable paste process for preparation is as follows:
(1) oil phase preparation: get white vaseline, octadecanol, liquid paraffin, peregal A-20 is placed in container, is heated to melting, and temperature remains on 90 ℃;
(2) water preparation: citric acid and sodium citrate are dissolved in water for injection, principal agent is dispersed in glycerol, propylene glycol, add the aqueous solution of citric acid and sodium citrate, ethyl hydroxybenzoate, heating, the temperature that stirs remains on 90 ℃;
(3) close phase: the oil phase of step (1) preparation is slowly added in the water of step (2) preparation, stir, maintain the temperature at 80 ℃, stir 30min, be cooled to cream, obtain 1000g emulsifiable paste, content 0.1%, recording mastic pH is 5.5.
preparation stability test 1
The hydrocortisone butyrate zinc oxide compound cream of Preparation Example 1-6 of the present invention is compared with the hydrocortisone butyrate zinc oxide emulsifiable paste of comparative examples 2, and stability obviously improves.We are according to the accelerated test method of two appendix 200-201 page stability of " Chinese Pharmacopoeia " version in 2010, investigate, sample is from FORMULATION EXAMPLE 1～4, the emulsifiable paste that each embodiment makes and comparative examples emulsifiable paste compare, 20 of every group of sample sizes, specification is that 10g/ props up, aluminum pipe packing, mainly liquid content and HCB-21 ester (hydrocortisone-21 butyrate) content are detected, according to Zhong Weigao, (HPLC method is measured hydrocortisone butyrate in hydrocortisone butyrate ointment to detection method, (Huai-Hai medicine, the 24th the 5th phase of volume of JIUYUE in 2006, 428-429) disclosed method detects.
Detecting instrument: Japanese Shimadzu LC-IOA high performance liquid chromatograph; SPD-l0A UV-detector
Chromatographic condition: chromatographic column, Shimadzu CIS-ODS post (150mm × 4.6mm, 5 μ are m); Mobile phase, methanol: water: ether (62:38:2); Flow velocity 1.0 ml/min; Sample size, 20 μ L; Column temperature, room temperature; Detect wavelength, UV240 nm.Theoretical cam curve is calculated and should be not less than 2 000 by hydrocortisone butyrate.The peak of hydrocortisone butyrate and the separating degree of adjacent impurity peaks meet the requirements.
The preparation of reference substance solution, precision takes hydrocortisone butyrate reference substance, and ((assay use, Products in China calibrating provides) 12.0mg, with mobile phase dissolving, and is settled to 100m1, shakes up.Be that concentration is the solution that every 1ml approximately contains 0.120mg.
The preparation of sample solution: the about 3.0g of sample thief emulsifiable paste.Accurately weighed, put in 50ml measuring bottle.Add methanol appropriate, put 80 ℃ water-soluble in, heating make dissolve, let cool to room temperature, add methanol and be diluted to scale, shake up.Put cooling 2 h in ice bath.After taking out, filter rapidly, discard just filtrate, get subsequent filtrate as sample solution.
Determining of linear relationship: precision takes hydrocortisone butyrate reference substance (content is 98.79%) 12.0 mg, with methanol solution and make every 1ml approximately containing the solution of 0.120 mg.Precision measures 4,8,10,12,16,20 ml and puts respectively in 50 m1 measuring bottles, adds methanol and is diluted to scale, shakes up.Under above-mentioned chromatographic condition, respectively sample introduction 20 μ L, result shows that hydrocortisone butyrate concentration and peak area in 30-45mg/L concentration range have good linear relationship.Regression equation Y=4475.3X+422.45.r＝0.9993。
Sample determination: get the each 20 μ L sample introductions of reference substance solution and need testing solution, read peak area value, calculate content by external standard method.HCB-21 content assaying method is identical with hydrocortisone butyrate method.
Examine stability carries out the stability test under accelerated stability test (40 ℃ ± 2 ℃, relative humidity 75% ± 5%) according to the open method of 176 pages of Chinese medicine preparation stability test direction principles of 2005 editions appendix of Chinese Pharmacopoeia.
Table two kind of hydrocortisone butyrate zinc oxide emulsifiable paste accelerated stability investigation result (n=20, average ± s)
The emulsion of hydrocortisone butyrate sample being made by embodiment 1～4 in upper table and comparative examples stability of cream Data Comparison can be found: after the accelerated stability experiment of 6 months, the active constituent content of the sample that the embodiment of the present invention provides is all higher than contrast emulsifiable paste, significantly lower than contrast emulsifiable paste (P < 0.01), this has absolutely proved that the emulsifiable paste making according to the embodiment of the present invention is better than commercially available stability of cream to the corresponding sample providing as the HCB-21 content embodiment of the present invention of major impurity, the impurity HCB-21 content that major impurity---ester exchange reaction produces is lower.In addition in accelerated stability is investigated, all there is not layering, metachromatism in the emulsifiable paste making by the present invention program.
the therapeutic effect of the allergic skin inflammation that pharmacology embodiment 1 causes mice fungal infection
Laboratory animal: Kunming kind outbreeding system healthy mice, weight 25-30g, male and female half and half
Modeling medicine: DNF (DNFB)
Experimental model: mice is in testing first 1 day in abdominal part unhairing, area is 2cm × 1.5cm, test and within the 1st day and the 2nd day, be coated with 0.5%DNFB25 μ L in abdominal part unhairing position, every day 1 sensitization, within the 6th day, bring out dermatitis in left hard of hearing the painting 0.25%DNFB20 μ L of mice, excited once every 3 days, auris dextra is carried on the back not coating and is formed blank again.
Mice random packet, every group 10, be divided into experimental group, positive controls, negative control group, experimental group divides into groups according to following table, and hard of hearing evenly smear Experimental agents 2 time Mus is left the 7th day to the 13rd day every day, 6 hours, interval between 2 times, the each dosage of each group is identical, and slightly massage is first coated with comparative examples 1-1 when packet number is 1-12 medication every day, interval after 30 minutes cleans up left ear water, then with the medicine coating of comparative examples 1-2.
Positive controls: all coatings not of the Mus left and right ear after this group modeling success, all the other same experimental grouies.
Negative control group: this group is not modeling healthy rat.。
Observation index: respectively organize first 1 hour of the 1st administration in the 7th day and medication in the 12nd day after 1 hour, etherization mice use micrometer apart from Mus basal part of the ear 1mm place detect thickness, calculates rear left auris dextra thickness difference at mice left and right ear middle part; Within the 13rd day, put to death mice, every mice is punched apart from Mus basal part of the ear 1mm place at mice left and right ear middle part with diameter 6mm metal card punch after putting to death immediately, gets ear tissue piece, at once weighs with analytical balance, calculates left and right ear of poor quality.
Experimental group administration and grouping see the following form:
Experimental result data is as following table: (X average ± s, n=10)
| Packet number | (μ m) for the 7th day administration front left auris dextra thickness difference | (μ m) for the 12nd day administration rear left auris dextra thickness difference | The 13rd day left and right ear (mg) of poor quality |
| Negative control group | 0.74±0.14 | 0.77±0.16 | 0.81±0.15 |
| Positive controls | 12.21±1.38 | 13.58±1.61 | 2.96±0.61 |
| 1-1 | 11.88±1.31 | 7.85±1.16 | 1.70±0.33 |
| 1-2 | 11.96±1.48 | 7.97±1.21 | 1.76±0.38 |
| 1-3 | 12.20±1.37 | 9.19±1.38 | 2.03±0.45 |
| 1-4 | 12.12±1.47 | 8.41±1.26 | 1.82±0.41 |
| 1-6 | 12.07±1.39 | 9.76±1.20 | 2.16±0.38 |
| 1-7 | 11.99±1.50 | 10.15±1.31 | 2.23±0.41 |
| 1-8 | 12.05±1.49 | 10.23±1.08 | 2.24±0.35 |
| 1-9 | 12.14±1.31 | 10.38±1.15 | 2.28±0.39 |
| 1-10 | 12.03±1.42 | 10.40±1.31 | 2.28±0.42 |
| 1-11 | 12.09±1.41 | 11.12±1.52 | 2.65±0.68 |
| 1-12 | 12.16±1.34 | 9.36±1.42 | 1.92±0.57 |
Experimental results show that by above-mentioned, zinc oxide uses with independent use or combines to use to compare with hydrocortisone butyrate compound recipe has better curative effect, ought contain in addition in the oil phase of zinc oxide and add sodium lauryl sulphate and peregal A mixed surfactant, after adding peregal A mixed surfactant in water kind, more contribute to the raising of bioavailability, and improve curative effect.
Claims (8)
1. a pharmaceutical composition, is characterized in that containing active component hydrocortisone butyrate and zinc oxide.
2. a pharmaceutical composition, is characterized in that being made up of active component hydrocortisone butyrate and zinc oxide, pharmaceutic adjuvant that one or more are applicable to Transdermal absorption.
3. the compositions as described in claim 1,2, the 0.01-0.1% that the content that it is characterized in that hydrocortisone butyrate is composition weight, the 1-5% that the content of zinc oxide is composition weight.
4. the compositions as described in claim 1,2, is characterized in that having the unguentum of oil-in-water structure.
5. compositions as claimed in claim 6, is characterized in that zinc oxide is positioned at oil reservoir, and hydrocortisone butyrate is positioned at water layer.
6. the compositions as described in claim 1,2, it is characterized in that oil reservoir adjuvant contains as one or more compositions in oil phase substrate, the surfactant of pharmaceutically useful adjuvant, water layer adjuvant is made up of one or more and water in surfactant, wetting agent, PH regulator, antiseptic.
7. emulsifiable paste as claimed in claim 6, is characterized in that described oil phase substrate is one or more in vaseline, paraffin, liquid paraffin, lanoline, Cera Flava, dimethicone, stearic acid, hexadecanol, octadecanol, vegetable oil; Surfactant is one or more of soap class, fatty alcohol sulfate or sodium class, higher fatty acids class, polyhydric alcohol esters, polyoxyethylene ether apoplexy due to endogenous wind; Wetting agent is one or more in glycerol, propylene glycol, sorbitol, and antiseptic is one or more in benzalkonium bromide, benzalkonium chloride, parabens antiseptic, benzoic acid, sodium benzoate, sorbic acid; PH adjusting agent is one or more in phosphate buffer salt, Tris buffer salt, citrate buffer salt.
8. as the ointment as described in arbitrary in claim 1,2, the compound method of described emulsifiable paste is as follows:
(1) oil phase preparation: zinc oxide is mixed with surfactant, and temperature remains on 70-90 ℃, then take in oil phase substrate heating and melting and become solution, after both mixing, temperature remains on 70-90 ℃;
(2) water preparation: hydrocortisone butyrate micropowder is dispersed in the wetting agent of solvent, will adds the water heating of pH value regulator, surfactant, antiseptic, the temperature that stirs remains on 70-90 ℃; Then be added to the water and stir, temperature remains on 70-90 ℃; (3) close phase: the oil phase of step (1) preparation is slowly added in the water of step (2) preparation, stir, maintain the temperature at 70-90 ℃, stir 10-30min, be cooled to cream.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105596364A (en) * | 2014-10-14 | 2016-05-25 | 熊英 | Skin disease external application drug, preparation method and uses thereof |
| CN111743853A (en) * | 2019-03-29 | 2020-10-09 | 天津金耀集团有限公司 | External pharmaceutical composition of near-neutral hydrocortisone butyrate |
| CN114504548A (en) * | 2020-11-16 | 2022-05-17 | 湖北舒邦药业有限公司 | Ointment and preparation method thereof |
| WO2023170597A1 (en) * | 2022-03-08 | 2023-09-14 | Sila S.P.A. | Topical composition for treating injuries or cutaneous inflammatory states or proctological pathologies |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1150022A (en) * | 1996-09-20 | 1997-05-21 | 王国申 | Medicine having action of sterilizing and anti-inflammatory |
| CN101810566A (en) * | 2009-11-26 | 2010-08-25 | 天津金耀集团有限公司 | Hydrocortisone butyrate cream |
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2014
- 2014-03-11 CN CN201410086364.6A patent/CN103877117A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1150022A (en) * | 1996-09-20 | 1997-05-21 | 王国申 | Medicine having action of sterilizing and anti-inflammatory |
| CN101810566A (en) * | 2009-11-26 | 2010-08-25 | 天津金耀集团有限公司 | Hydrocortisone butyrate cream |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105596364A (en) * | 2014-10-14 | 2016-05-25 | 熊英 | Skin disease external application drug, preparation method and uses thereof |
| CN111743853A (en) * | 2019-03-29 | 2020-10-09 | 天津金耀集团有限公司 | External pharmaceutical composition of near-neutral hydrocortisone butyrate |
| CN114504548A (en) * | 2020-11-16 | 2022-05-17 | 湖北舒邦药业有限公司 | Ointment and preparation method thereof |
| CN114504548B (en) * | 2020-11-16 | 2023-08-22 | 湖北舒邦药业有限公司 | Ointment and preparation method thereof |
| WO2023170597A1 (en) * | 2022-03-08 | 2023-09-14 | Sila S.P.A. | Topical composition for treating injuries or cutaneous inflammatory states or proctological pathologies |
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Application publication date: 20140625 |