CN102379893A - Compound pharmaceutical composition of iodine polymer and glucocorticosteroid for treating dermatitis - Google Patents
Compound pharmaceutical composition of iodine polymer and glucocorticosteroid for treating dermatitis Download PDFInfo
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- CN102379893A CN102379893A CN2011102514190A CN201110251419A CN102379893A CN 102379893 A CN102379893 A CN 102379893A CN 2011102514190 A CN2011102514190 A CN 2011102514190A CN 201110251419 A CN201110251419 A CN 201110251419A CN 102379893 A CN102379893 A CN 102379893A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
- A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
- A61K31/79—Polymers of vinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
The invention relates to the field of medicinal preparation and relates to a compound pharmaceutical composition of iodine polymer and glucocorticosteroid for treating dermatitis. The pharmaceutical composition of the present invention comprises 0.01-5% of polyvinylpyrrolidone iodine, 0.01-10% of glucocorticosteroid, 0.001-0.5% of potassium iodate and the balance of pharmaceutically accepted carrier, wherein the glucocorticosteroid is fluticasone propionate or halometasone. Drug effect test has proved that the compound medicament can treat dermatitis by synergism; furtherly, addition of a certain proportion of potassium iodate overcomes unfavorable influences of drug effect decrease or auxiliary effect caused by medicament instability.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of iodine polymer and glucocorticoid compound medicament composition of treating dermatitis.
Background technology
Scytitis such as eczema (eczema), allergic dermatitis (allergic dermatitis), atopic dermatitis (atopic dermatitis), urticaria (Urticaria) etc. all are to be caused allergy and caused scytitis by certain allergen; The allergic effect that causes skin allergic reaction is original multiple; Wherein infection such as virus, fungus, antibacterial are one of major reasons that causes scytitis, and bacterial infection is an important sensitizing agent in the various skin inflammation such as allergic dermatitis.The glucocorticosteroid hormone is widely used in the treatment scytitis; But because the immunosuppressive action of glucocorticosteroid hormone; Make the glucocorticosteroid hormone when being used to treat the inflammation that the skin surface bacterial infection causes, not only can not reach antiphlogistic effect, can make the inflammation aggravation on the contrary.Influenced the application of glucocorticosteroid hormone when the treatment scytitis.Moreover because contingency dermatitis and noninfective allergic dermatitis that infection such as antibacterial cause are quite similar on surface symptoms, be difficult to differentiate as not adopting microscopic examination, dimension causes mistaken diagnosis clinically easily, thereby delay treatment.And the dermatosis that causes for infection such as skin bacteriums; Though in treatment, do not use the glucocorticosteroid hormone; But owing to the sensitization of microorganisms such as antibacterial, often be attended by the generation of allergic skin inflammation, adopt anti-bacterial drug to treat to the infection elimination; Animal often also has the inflammatory crust to exist, and explains that scytitis often more is difficult to treatment than infection itself.
Povidone iodine (PVP-I is called for short PI) is the complex of polyvinylpyrrolidone (PVP) and iodine, claims povidone iodine again, contains available iodine 9～12%, is a kind of broad-spectrum powerful disinfectant, and virus, antibacterial, fungus and mycotic spore are all had stronger killing action.Little to skin irritation, toxicity is low, persistent.Safe in utilization, easy.To organizing basic nonirritant, be used for the sterilization of skin and mucosa, as perform the operation preceding cleaning, operative site and wound disinfection.Its sterilizing mechanisms mainly is through discharging free hydration iodine performance bactericidal action; The polyvidone possess hydrophilic property; Be the carrier that iodine is delivered to cell membrane, after complex touched cell wall, the free-iodine that discharges and the aminoacid of tropina combined; Make its degeneration, the proteic active group of simultaneous oxidation antibacterial oleo stock and make microorganism dead rapidly.The common working concentration of betagen solution is 0.1%～10%.Existing Acu-Dyne is mainly povidone iodine gel agent, suppository, ointment, solution, and content 1%～10% does not wait (Chinese Pharmacopoeia 2010 editions).
Fluticasone propionate (fluticasone propionate) is a glucocorticoid medicine, have strong effect local anti-inflammatory and anti-allergic effects, toleration is preferably arranged.Be applicable to the struvite and itching skin disease that various 17-hydroxy-11-dehydrocorticosterone can be alleviated, as: eczema comprises specificity eczema and plate-like eczema; Prurigo nodularis; Psoriasis (except general the speckle type); Nervous dermatoses comprises simple property lichen; Lichen planus; Seborrheic dermatitis; Contact is irritated; The dish type lupus erythematosus; The adjuvant drug of generalized erythema whole body steroid hormone treatment, insect dermatitis; Miliaria.For the child: one-year-old above (containing one-year-old) child available inflammation and pruritus that article alleviation atopic dermatitis causes under doctor's guidance that the poor efficiency 17-hydroxy-11-dehydrocorticosterone is invalid.Existing fluticasone propionate or halometasone preparation are mainly ointment, solution, nasal spray.Content 0.1%～1% does not wait.
Halometasone (Halometasone), halometasone are strong effect external glucocorticoid medicines that contains halogen.It has antiinflammatory, antiallergic, vasoconstrictive and anti-proliferative effect.Sick for the inflammatory skin of a lot of types and different reasons, it can very promptly alleviate and eliminate, for example symptom such as pruritus.Experimental studies results shows, the multiple drug action of glucocorticoid is attributable to the mechanism of the molecular level of it and the special cytosol receptor complicacy due to interacting.
Invent the compound preparation of povidone iodine and 17-hydroxy-11-dehydrocorticosterone in inventor's early-stage Study, be used for the treatment (CN200780008873.5) of ocular disease.One Chinese patent application CN200910228785.7 discloses a kind of local topical compositions that contains povidone iodine and cyclodextrin inclusion compound glucocorticoid.In order to overcome the instability of medicine, this patent has been taked cyclodextrin inclusion technique.As everyone knows, cyclodextrin inclusion technique because 1, the enclose material is limited, and organic stronger hematotoxicity and damaging nephrotoxicity of causing easily such as acetone, ethanol are often arranged in the preparation process, is unfavorable for health.2, molecular size, polarity and the structure etc. to the enclose medicine have restriction, because glucocorticoid molecular size, polarity, structure are all inequality, so cyclodextrin inclusion technique is not ubiquitous.3, the inside and outside of clathrate stability: vitro stability depends on polarity and the power of molecular separating force between host and guest's molecule; Can medicine be replaced through the competition displacement in the body, cause the medicine rapid release.4, the envelop rate of cyclodextrin inclusion compound is not high, causes having strengthened in the technical process difficulty.5, behind the cyclodextrin inclusion compound there is unknown influence in the release of medicine,, may causes not reaching the concentration medicine that to keep owing to release insufficient like releases degree.Therefore finding one, can effectively to solve this circumscribed method be a very important problem.
Summary of the invention
The invention discloses a kind of compound medicament composition of treating dermatitis, its active component is made up of povidone iodine and fluticasone propionate or halometasone, and the test of pesticide effectiveness proves that this compound medicine reaches synergism.In addition, through adding a certain proportion of potassium iodate, overcome again that drug effect that the medicine instability causes descends or adverse effect such as side effect.
Be detailed description of the present invention below:
Pharmaceutical composition of the present invention is made up of 0.01%～5% povidone iodine, 0.01%～10% glucocorticoid, 0.001%～0.5% potassium iodate and the pharmaceutically acceptable carrier of surplus; Wherein glucocorticoid is fluticasone propionate or halometasone; Percentage ratio of the present invention all is weight percentage, and each percentages of ingredients of the present invention is in the shared percentage ratio of this component of total formulation weight amount.
Povidone iodine content is preferred 0.01%～2%, fluticasone propionate or halometasone content preferred 0.01%～2%.
Povidone iodine content more preferably 0.01%～1%, fluticasone propionate or halometasone be content preferred 0.01%～1% more.
Fluticasone propionate or halometasone preferably carry out the preparation preparation again behind micronization.
Compound preparation of the present invention selects suitable pharmaceutically acceptable carrier can be prepared into multiple dosage form, is preferably semi-solid solution or suspension.Preferred dosage form is ointment, ointment, gel, suspensoid, spray, transdermal patch or liniment.
Compound preparation of the present invention; Except containing active component and solvent; Also preferably contain in pH regulator agent, surfactant, viscosity modifier, consistency modifiers, suspending agent, oil-phase component, rheology control agent, consistency modifiers, emulsifying agent, wetting agent, stabilizing agent, osmotic pressure regulator, the complexing of metal ion agent one or more and the water of surplus.
Described surfactant can be polysorbate 20, polysorbate 60, Tween 80, polyoxyethylene surfactant, cyclodextrin, thyrode sand primary, Polyethylene Glycol, Oleum Ricini, Polyethylene Glycol 40, stearic acid etc.Total formulation weight amount meter, generally, the addition of surfactant is 0.01% to 2% weight classes.Preferred Tween 80 or thyrode husky primary.Surface-active contents preferred 0.01%～0.5%.
Described suspending agent can be methylcellulose, hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, microcrystalline Cellulose or sodium carboxymethyl cellulose etc.Preferably microcrystalline cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, suspending agent preferably account for 0.01%～2% of irrigation gross weight.
Described osmotic pressure regulator can be glycerol, mannitol, sorbitol, sodium chloride or other electrolyte.Preferred sodium chloride.Osmotic pressure regulator preferably accounts for 0.03%～2% of irrigation gross weight.
Described viscosity modifier can be enumerated but be not limited only to sodium carboxymethyl cellulose, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, carboxy vinyl polymer, polyvinyl pyrrolidone etc., consumption preferred 0.1%～2%.Said viscosity modifier also can be used as suspending agent.
Described pH regulator agent is for enumerating but be not limited only to phosphoric acid and salt, boric acid and salt thereof, citric acid and salt thereof, acetic acid and salt thereof, tartaric acid and salt thereof, hydrochloric acid, sodium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, tromethane etc.Preferred hydrochloric acid or sodium hydroxide.
Said wetting agent can be enumerated but be not limited only to glycerin, propylene glycol or sorbitol.Preferred glycerin.Said wetting agent consumption preferred 4%～10%, preferred especially 5%.
Compound preparation of the present invention also can contain complexing of metal ion agent EDTA-Na, and the complexing of metal ion agent accounts for 0.01%～0.05% of total formulation weight amount.
When part according to the invention made pharmaceutical composition process gel, described adjuvant contained water and is the carbomer resin as rheology control agent.Be preferably carbomer 934 and/or Acritamer 940 and/or Carbopol 941 especially, consumption is 0.1%～1%. preferred 0.2% to 0.5% of a pharmaceutical composition weight.
When part of the present invention makes pharmaceutical composition process ointment; Described adjuvant contains wetting agent, oil-phase component 10%～50%; Said wetting agent includes but are not limited to glycerol, propylene glycol or sorbitol; Consumption is 1%～15%, and preferably glycerine, described oil-phase component comprise one or more in solid in the oil-phase component, consistency modifiers, the emulsifying agent.
Solid includes but are not limited to one or more of stearic acid, paraffin, Cera Flava, higher alcohol in the said oil-phase component, and described higher alcohol is the monohydric alcohol of 16～22 carbon atoms, preferred hexadecanol with or octadecanol, said oil-phase component consumption is 1%～45%.
Described consistency modifiers includes but are not limited to one or more in vaseline, liquid paraffin, vegetable oil, the polyacrylic resin, preferred vaseline with or polyacrylic resin, the consumption of described consistency modifiers is 50%～70%.
Described emulsifying agent; Include but are not limited to soap class emulsifying agent; The derivant of polyoxyethylene ether, preferably as the glyceryl monostearate of soap class emulsifying agent with or as the peregal A-20 of polyoxy ether class emulsifying agent, total consumption 1～18% of said emulsifying agent; Preferred soap class emulsifying agent consumption is 0.5%～10%, and polyoxy ether class emulsifying agent consumption is 0.5～8%.
Described higher alcohol also plays influence of surfactant simultaneously in emulsifiable paste.Percentage ratio of the present invention is relative pharmaceutical composition and gets percentage by weight.
The preferred 4-8 of compound medicament composition pH of the present invention.
Described pharmaceutical composition can be prepared in order to following method:
The preparation of compound recipe fluticasone propionate or halometasone suspension:
Fluticasone propionate or halometasone are carried out after fully sparing matter on the homogenizer, placing container with water, suspending agent, osmotic pressure regulator with non-ionic surface active agent behind the micronization, after stirring, obtain the principal agent suspension;
Get proper amount of water for injection, other adjuvant dissolvings that add recipe quantity stir, and add the povidone iodine dissolving of recipe quantity, mix with fluticasone propionate or halometasone suspension, add water for injection to recipe quantity, and packing promptly gets.
When said preparation of pharmaceutical compositions becomes ointment, can prepare in order to following method:
The preparation of oil phase
Oil phase (comprising: hexadecanol, white vaseline, liquid paraffin, stearic acid, the glyceryl monostearate) composition of getting recipe quantity is heated to fusing (60 ℃～80 ℃), and stirring promptly gets.
The preparation of emulsifiable paste
Obtain fluticasone propionate or halometasone suspension through fluticasone propionate behind the abundant homogenizing micronization of surfactant or halometasone, be heated to 60 ℃～80 ℃, add the povidone iodine dissolving of recipe quantity; And be heated to the wetting agent glycerol of same temperature, and stir, add the emulsifying agent of recipe quantity; Add oil phase, stir emulsifying 2 hours; After the emulsifying evenly, condensation promptly gets, and divides to be filled in the aluminum pipe.
When said preparation of pharmaceutical compositions becomes gel, can prepare in order to following method:
Be not limited only to Carbopol 941 put into the water for injection swelling about 12-24 hour after, behind fluticasone propionate or halometasone micronization, add the fully even matter of surfactant after; By the time uniform and stable suspension; And join in the swelling solution, add other adjuvant, and both stir.
When said preparation of pharmaceutical compositions becomes transdermal patch, can prepare in order to following method:
With the even back adding of fully even matter povidone iodine behind fluticasone propionate behind the micronization of recipe quantity or the halometasone adding surfactant; In adding pressure sensitive adhesive, and reconcile into suitable denseness, be coated on the protective layer with consistency modifiers; The thickness of control coating; The decompression oven dry is covered with backing layer, cuts into suitable size and shape and gets final product.
When said preparation of pharmaceutical compositions becomes liniment, can prepare in order to following method:
With the even back adding of fully even matter povidone iodine behind fluticasone propionate behind the micronization of recipe quantity or the halometasone adding surfactant; Fully stir the back and add propylene glycol, penetrating agent, osmotic pressure regulator, pH regulator agent; Add an amount of water, stirring both got.
The present invention processes compound preparation with povidone iodine and fluticasone propionate or halometasone, and the oxidized or fluticasone propionate of iodine or halometasone unfavorable phenomenon such as be degraded does not appear in the result.Compound preparation of the present invention also has good therapeutic efficiency to the infection that treatment occurs during dermatitis; Kill bacteria, fungus, virus etc. during the treatment inflammation; When treatment mixed infection and inflammation, use emulsifiable paste to put skin on the skin and can cure infection and inflammation, can also treat dysplastic type reactive inflammation and operation back inflammation infection etc.We are surprised to find compound preparation and have good synergism through the zoopery pharmacological datum, so we estimate that the using dosage that can reduce glucocorticoid and povidone iodine reaches drug effect likewise, reduces the toxic and side effects to human body simultaneously.
Be the part pharmacodynamics test and the result of compound preparation of the present invention below:
Povidone iodine and fluticasone propionate or halometasone combination are to the therapeutic effect of Cavia porcellus staphylococcus aureus skin infection
1, laboratory animal:
1.1 source, kind, the quality certification: albino guinea-pig, regular grade.
1.2 body weight: 250～300g
1.3 the age: grow up
1.4 sex: male and female half and half
1.5 number of animals: 72
2, receive reagent:
2.1 fluticasone propionate compound cream high dose group: 1% povidone iodine+0.05% fluticasone propionate compound cream, 10 grams/
2.2 fluticasone propionate compound cream low dose group: 0.5% povidone iodine+0.025% fluticasone propionate compound cream, 10 grams/
2.3 halometasone compound cream high dose group: 1% povidone iodine+0.05% halometasone compound cream, 10 grams/
2.4 halometasone compound cream low dose group: 0.5% povidone iodine+0.025% halometasone compound cream, 10 grams/
2.5 the povidone iodine emulsifiable paste side of tearing open group: 1% povidone iodine emulsifiable paste, 10 grams/
2.6 the fluticasone propionate emulsifiable paste side of tearing open group: 0.05% fluticasone propionate emulsifiable paste, 15 grams/
2.7 the halometasone emulsifiable paste side of tearing open group: 0.05% halometasone emulsifiable paste, 10 grams/
2.8 emulsifiable paste matrix matched group
2.9 erythromycin ointment positive controls: 1% erythromycin ointment, 10 grams/
3, the preparation of infection bacteria species:
Staphylococcus aureus is seeded to the agar slant incubated overnight from the glycerol pipe, is forwarded to meat soup, 37 ℃ leave standstill cultivation 8h.Be forwarded to again and shake bottle and (200 change/min), cultivate behind the 14h that centrifugal (10min 8000 changes/min), the normal saline washed twice with equal volume is adjusted to 1.2 * 10 with bacterium liquid with culture for 37 ℃
10CFU/ml is subsequent use.
4, experimental technique:
Cavia porcellus is sloughed the back by hair, the about 5 * 6cm of depilation area
2, and draw long " well " word of 1.5cm, with scratch corium, oozing of blood is a standard, skin surface is coated with staphylococcus aureus liquid, and injects the 0.2ml original bacteria liquid at the Intradermal of " well " word central part, occurs red and swollen suppurative infection behind the 24h.Cavia porcellus is divided into above-mentioned 9 groups at random, on the skin of infection site, smears corresponding medicine respectively, every day 1 time is with the positive contrast medicine of erythromycin ointment, the negative contrast of emulsifiable paste matrix.Successive administration 3 days, the 4th day observed result writes down situation such as coating part erythema and edema, and marks by the standards of grading of table 1.Cavia porcellus eye socket venous plexus is got blood; Separation of serum; Measure the content of lysozyme in the serum by lysozyme test kit method (bio-engineering research institute is built up in Nanjing); Last each group is got 3 examples at random and is infected local skin, 10% formalin fixed, and dehydration, FFPE, section (4 μ m), HE dyeing, light microscopic are observed histopathology down and are changed.
Table 1 scytitis standards of grading
| Reaction | Score value |
| Erythema: | |
| No erythema | 0 |
| Slight erythema (visible reluctantly) | 1 |
| Moderate erythema (obviously visible) | 2 |
| The severe erythema | 3 |
| The aubergine erythema is to there being slight eschar to form | 4 |
| Edema: | |
| No edema | 0 |
| Mild edema (visible reluctantly) | 1 |
| Intermediate edema (obviously protuberance) | 2 |
| Severe edema (the about 1mm of skin, profile is clear) | 3 |
| Serious edema (skin 1mm above and have expansion) | 4 |
5, experimental result:
5.1 povidone iodine and fluticasone propionate or halometasone combination are to the influence of Cavia porcellus infection of staphylococcus aureus red swelling of the skin situation
Table 2 povidone iodine and fluticasone propionate or halometasone combination are to the influence of the scorching red swelling of the skin situation of Cavia porcellus gold Portugal's mycoderma
5.2 povidone iodine and fluticasone propionate or halometasone combination are to the influence of lysozyme content in the Cavia porcellus infection of staphylococcus aureus serum
The influence of lysozyme content in the serum is infected in table 3 povidone iodine and fluticasone propionate or halometasone combination to Cavia porcellus gold Portugal bacterium
Compare with matrix group,
*P＜0.05,
*P＜0.01
Compare #p＜0.05, ##p＜0.01 with halometasone, the fluticasone propionate emulsifiable paste side of tearing open group respectively
Compare △ p＜0.05, △ △ p＜0.01 with the povidone iodine emulsifiable paste side of tearing open group
5.3 povidone iodine and fluticasone propionate/halometasone combination is to the influence of Cavia porcellus infection of staphylococcus aureus dermal pathology Histological change
5.3.1 halometasone compound cream preparation high dose group: 3 routine skin surface lining squamous epithelial cancers are still complete, wherein see the little purulence focus of kitchen range shapeization in the 1 routine skin corium; Appendages such as the interior hair follicle of high dermis are still complete.
5.3.2 halometasone compound cream preparation low dose group: 1 routine skin surface lining squamous epithelial cancer special mess shape degeneration, necrosis, the subregion decrustation, all the other 2 routine skin surface lining squamous epithelial cancers are still complete; The visible suppurative focus of special mess shape in the 2 routine skin coriums; Appendages such as the interior hair follicle of high dermis are still complete.
5.3.3 fluticasone propionate compound cream preparation high dose group: 1 routine skin surface lining squamous epithelial cancer special mess shape degeneration, necrosis, the subregion decrustation, all the other 2 routine skin surface lining squamous epithelial cancers are still complete; The visible suppurative focus of special mess shape in the 1 routine skin corium; Appendages such as the interior hair follicle of high dermis are still complete.
5.3.4 fluticasone propionate compound cream preparation low dose group: 1 routine skin surface lining squamous epithelial cancer special mess shape degeneration, necrosis, the subregion decrustation, all the other 2 routine skin surface lining squamous epithelial cancers are still complete; All see the suppurative focus of special mess shape in the 2 routine skin coriums; Appendages such as the interior hair follicle of high dermis are still complete.
5.3.5 the povidone iodine emulsifiable paste side of tearing open group: 2 routine skin surface lining squamous epithelial cancer special mess shape degeneration, necrosis, the subregion decrustation, all the other 1 routine skin surface lining squamous epithelial cancers are still complete; All see the suppurative focus of special mess shape in the 3 routine skin coriums; Appendages such as the interior hair follicle of high dermis are still complete.
5.3.6 the halometasone emulsifiable paste side of tearing open group: 2 routine skin surface lining squamous epithelial cancer special mess shape degeneration, necrosis, the subregion decrustation, all the other 1 routine skin surface lining squamous epithelial cancers are still complete; The visible suppurative focus of special mess shape in the 2 routine skin coriums; Appendages such as the interior hair follicle of high dermis are still complete.
5.3.7 the fluticasone propionate emulsifiable paste side of tearing open group: 2 routine skin surface lining squamous epithelial cancer special mess shape degeneration, necrosis, the subregion decrustation, all the other 1 routine skin surface lining squamous epithelial cancers are still complete; All see the suppurative focus of special mess shape in the 2 routine skin coriums; Appendages such as the interior hair follicle of high dermis are still complete.
5.3.8 emulsifiable paste matrix negative control group: 3 routine skin surface lining squamous epithelial cancer special mess shape degeneration, necrosis, subregion decrustation; All see the suppurative focus of special mess shape in the 3 routine skin coriums; Appendages such as the interior hair follicle of high dermis are still complete.
5.3.9 erythromycin ointment positive controls: 3 routine skin surface lining squamous epithelial cancers are still complete, wherein see the suppurative focus of special mess shape in the 2 routine skin coriums; Appendages such as the interior hair follicle of high dermis are still complete.
6, judged result:
Can find out from experimental result, adopt the compound experimental group of povidone iodine of the present invention and halometasone to compare with the substrate negative control group, the red and swollen situation of guinea pig back also is clearly better; The content of lysozyme significantly increases in the serum; The histopathology observed result shows; Compare (seeing Figure 15,16) with the epithelial layer and the skin corium of emulsifiable paste matrix negative control group; Halometasone compound cream preparation is to the degeneration of skin surface lining squamous epithelial cancer special mess shape, necrosis; The symptom of subregion decrustation is greatly improved, skin surface lining squamous epithelial cancer complete basically (seeing Fig. 1,3), and the suppurative focus of special mess shape alleviates (seeing Fig. 2,4) in the skin corium; Halometasone compound cream preparation has significant therapeutical effect to Cavia porcellus infection of staphylococcus aureus dermatitis.The compound experimental group of povidone iodine and fluticasone propionate is compared with the substrate negative control group, and the red and swollen situation of guinea pig back is clearly better; The content of lysozyme significantly increases in the serum; The histopathology observed result shows; Compare (seeing Figure 15,16) with the epithelial layer and the skin corium of emulsifiable paste matrix negative control group; The third fluoric acid fluticasone compound cream preparation group is to the degeneration of skin surface lining squamous epithelial cancer special mess shape, necrosis; The symptom of subregion decrustation is greatly improved, skin surface lining squamous epithelial cancer complete basically (seeing Fig. 5,7), and the suppurative focus of special mess shape alleviates (seeing Fig. 6,8) in the skin corium; Fluticasone propionate compound cream preparation has certain therapeutical effect to Cavia porcellus infection of staphylococcus aureus dermatitis.Compare with the side's of tearing open group of povidone iodine emulsifiable paste, glucocorticoid halometasone emulsifiable paste and fluticasone propionate emulsifiable paste, the red and swollen situation of the guinea pig back of compound recipe group is clearly better; Lysozyme content significantly increases in the serum; The histopathology observed result shows; Compare (seeing Fig. 9,10,11,12,13,14) with the side's of tearing open group of povidone iodine emulsifiable paste, glucocorticoid halometasone emulsifiable paste and fluticasone propionate emulsifiable paste; The compound preparation group of povidone iodine and fluticasone propionate or halometasone combination is to the degeneration of skin surface lining squamous epithelial cancer special mess shape, necrosis; The symptom of subregion decrustation has greatly improved (seeing Fig. 1,3,5,7), and the suppurative focus of special mess shape alleviates (seeing Fig. 2,4,6,8) in the skin corium; The erythromycin ointment positive controls; Skin surface lining squamous epithelial cancer is still complete; See the suppurative focus of special mess shape in the skin corium; Appendages still complete (seeing Figure 17,18) such as the interior hair follicle of high dermis, the compound preparation group curative effect of povidone iodine and fluticasone propionate or halometasone combination is superior to the respectively side's of tearing open group, and compound medicine has produced synergism.
As everyone knows, because the high potential of iodine molecule and sugared cortex chemical reaction, iodine and iodine discharge iodophor and most sugars cortex can not be compatible.We effectively suppress povidone iodine and decompose the stability that keeps low concentration, and reduced the toxic and side effects that potassium iodate might produce through suitably adding the potassium iodate of trace.We preferably adopt even matter and micronization technology during preparation, and the glucocorticoid bad to dissolubility has general applicability, and technological operation is simple, and is quality controllable, do not influence the normal drug release rate of 17-hydroxy-11-dehydrocorticosterone, do not change its normal curative effect.The symptom that allergy causes when having avoided independent use glucocorticoid or povidone iodine is eliminated slow characteristics; Also overcome glucocorticoid and can not be applied to the scytitis that bacterial infection causes; The decline of immunocompetence causes the shortcoming of superinfection risk; When having improved curative effect, also enlarge the scope of application, reduced the incidence rate of mistaken diagnosis.Stability test shows that compound preparation of the present invention need not add benzalkonium chloride, imidazolidinyl urea and other deleterious antiseptic, need not to add other materials and prolongs the storage time.
Be the segmental stability test below
Test method: get 7 trial drugs for every group,, carry out stability test under the situation of relative humidity 75% ± 5% at 40 ℃ ± 2 ℃.
Sampling is tested each 2 during respectively at 0 day, 5 days, 10 days.Carry out the detection of character, pH value, available iodine content.
Available iodine content adopts titrimetry to measure, and every test specimen is pipetted about 110 grams to the beaker of 250ml; Fully dissolve with purified water,, disappear with 0.01N sodium thiosulfate solution titrated to brown up to not dissolving fully; Confirm the volume of used sodium thiosulfate, calculate available iodine.
Result of the test:
Stability experiment shows that povidone iodine and halometasone or fluticasone propionate do not have interaction, and povidone iodine has extraordinary effect in the compound preparation to stablizing to add potassium iodate.
Description of drawings
Fig. 1 is the epithelial layer of halometasone compound cream preparation high dose group.
Fig. 2 is the skin corium of halometasone compound cream preparation high dose group.
Fig. 3 is the epithelial layer of halometasone compound cream preparation low dose group.
Fig. 4 is the skin corium of halometasone compound cream preparation low dose group.
Fig. 5 is the epithelial layer of fluticasone propionate compound cream preparation high dose group.
Fig. 6 is the skin corium of fluticasone propionate compound cream preparation high dose group.
Fig. 7 is the epithelial layer of fluticasone propionate compound cream preparation low dose group.
Fig. 8 is the skin corium of fluticasone propionate compound cream preparation low dose group.
Fig. 9 is the epithelial layer of the povidone iodine emulsifiable paste side of tearing open group.
Figure 10 is the skin corium of the povidone iodine emulsifiable paste side of tearing open group.
Figure 11 is the epithelial layer of the halometasone emulsifiable paste side of tearing open group.
Figure 12 is the skin corium of the halometasone emulsifiable paste side of tearing open group.
Figure 13 is the epithelial layer of the fluticasone propionate emulsifiable paste side of tearing open group.
Figure 14 is the skin corium of the fluticasone propionate emulsifiable paste side of tearing open group.
Figure 15 is the epithelial layer of emulsifiable paste matrix negative control group.
Figure 16 is the skin corium of emulsifiable paste matrix negative control group.
Figure 17 is the epithelial layer of erythromycin ointment positive controls.
Figure 18 is the skin corium of erythromycin ointment positive controls.
The specific embodiment
Embodiment 1
The preparation of PVP-I (0.1%) fluticasone propionate (0.01%) compound recipe suspension
| Component | Consumption (gram) |
| Fluticasone propionate | 0.24 |
| Povidone iodine | 2.4 |
| Potassium iodate | 0.072 |
| Plain 591 (microcrystalline Cellulose and the sodium carboxymethyl cellulose) of Ai Wei | 15 |
| Sodium chloride | 4 |
| Thyrode husky primary | 0.39 |
| ?EDTA-Na | 0.25 |
Method for preparing:
The fully even matter of the husky uncle of thyrode that in the 40g sterilized water, adds micronized fluticasone propionate of 0.24g and recipe quantity successively adds microcrystalline Cellulose and sodium carboxymethyl cellulose, sodium chloride, EDTA-Na and pure water more than 12 hours again, forms suspensoid.With dry powder, the potassium iodate of 2.4g povidone iodine, be dissolved in this suspending agent.Add about 2000mL water in irrigator bottle, add sodium hydroxide and regulate pH value to 4.0,, make to contain 0.1%PVP-I in the suspensoid solution, contain 0.01% fluticasone propionate quantitatively to 2400 grams.
Embodiment 2
The preparation of PVP-I (0.5%) fluticasone propionate (0.025%) ointment
| Component | Consumption (gram) |
| Fluticasone propionate | 0.06 |
| Povidone iodine | 1.2 |
| Hexadecanol | 2 |
| Potassium iodate | 0.0072 |
| Sodium lauryl sulphate | 2.1 |
| White vaseline | 33.5 |
| Liquid paraffin | 13.5 |
| Glycerol | 11.2 |
| Stearic acid | 9 |
| Glyceryl monostearate | 8 |
| Water for injection | 159.4 |
| Tween 80 | 0.09 |
| EDTA-Na | 0.025 |
Method for preparing:
1, the povidone iodine of recipe quantity, potassium iodate add in the 20 gram waters for injection, dissolve in advance solution A, in 55 ℃ of water-baths, be incubated.
2, micronized fluticasone propionate adds 20 gram water and adds in the Tween 80, EDTA-Na of recipe quantity, even matter more than 12 hours in homogenizer, solution B, in 55 ℃ of water-baths, be incubated.
3, the hexadecanol, white vaseline, liquid paraffin, stearic acid, single stearic acid glyceride, heating in water bath to 80 ℃ that in the 250ml beaker, add recipe quantity respectively; Stir after the thawing Deng fully; Again solution A, sodium lauryl sulphate, solution B are slowly added wherein successively after slowly being cooled to 55 ℃ and under the high speed dispersing emulsification machine, keep 55 ℃ of temperature breasts to spare 2 hours; Then recipe quantity glycerol is slowly added wherein successively; Stir (mechanical agitation 800rpm half an hour), regulate pH to 4. with 0.1mol or 1NaOH
4, keep 30 ℃ of bath temperatures, fill is to aluminum pipe rapidly.
Make and contain 0.5%PVP-I in the ointment, contain 0.025% fluticasone propionate.Said mixture is cream preparation and makes flow process.This ointment is applicable to the treatment of dermatitis.
Embodiment 3
The preparation of PVP-I (1%) fluticasone propionate (0.5%) gel
| Component | Consumption (gram) |
| Fluticasone propionate | 1.2 |
| Povidone iodine | 2.4 |
| Potassium iodate | 0.0072 |
| Carbopol 941 | 1 |
| Sodium chloride | 0.4 |
| Poloxamer | 0.8 |
| EDTA-Na | 0.0244 |
Method for preparing:
The Carbopol 941 of recipe quantity is gone in the 100 gram water, and swelling 24 hours obtains even swelling solution A.
The even matter of poloxamer that the micronized fluticasone propionate of recipe quantity is added recipe quantity is more than 12 hours, suspension B.
Prepare povidone iodine, above-mentioned swelling solution A, Carbopol 941, above-mentioned suspension B, sodium chloride, potassium iodate, EDTA-Na and the water for injection of 2.4 grams; According to, add sodium hydroxide and regulate pH value to 4.0, add water quantitatively to gross weight 240 grams; After heated and stirred is even, put cold.Said mixture is the gel of 1% povidone iodine, 0.5% fluticasone propionate.
Embodiment 4
The preparation of PVP-I (2%) fluticasone propionate (1%) spray
| Component | Consumption (gram) |
| Fluticasone propionate | 2.4 |
| Povidone iodine | 4.8 |
| Potassium iodate | 0.0072 |
| Hydroxyethyl-cellulose | 1.2 |
| Sodium chloride | 0.4 |
| PEG4000 | 1.2 |
| EDTA-Na | 0.0244 |
Method for preparing:
The micronized fluticasone propionate of the process of recipe quantity adds the PEG4000 of recipe quantity, and fully even matter obtained suspension A more than 12 hours.
With the abundant mixing and stirring of povidone iodine, potassium iodate, A, hydroxyethyl-cellulose, sodium chloride, EDTA-Na and pure water of 4.8g, add sodium hydroxide and regulate pH value to 4.0, add water quantitatively to gross weight 240 grams.Pack into inside the dosing container, install pressue device additional, promptly get spray, the spray of said mixture 5% povidone iodine, 1% fluticasone propionate.
Embodiment 5
The preparation of PVP-I (4%) fluticasone propionate (1%) transdermal patch
| Component (drug storehouse layer) | Consumption (gram) |
| Fluticasone propionate | 1.85 |
| Povidone iodine | 7.4 |
| Potassium iodate | 0.0056 |
| Polyacrylic resin | 11.7 |
| Ethyl acetate | 5.6 |
| Lauryl alcohol | 0.93 |
| Lecithin | 0.93 |
| Component (adhesion layer) | Consumption (gram) |
| Fluticasone propionate | 0.55 |
| Povidone iodine | 2.2 |
| Potassium iodate | 0.0016 |
| Polyacrylic resin | 12.1 |
| Ethyl acetate | 5.87 |
| Lauryl alcohol | 0.93 |
| Lecithin | 0.27 |
Method for preparing:
The fluticasone propionate of recipe quantity adds the lecithin of recipe quantity, and fully even matter obtained suspension A more than 12 hours in 50 gram water.With the abundant mixing and stirring of povidone iodine, potassium iodate, A and pure water of 9.6g, add sodium hydroxide and regulate pH value to 4.0, obtain B.With B according to the ratio of drug storehouse layer specific adhesion layer=10 to 3 respectively at polyacrylic resin, ethyl acetate, lauryl alcohol mix homogeneously according to recipe quantity.Be coated with into certain thickness; At 60 ℃-80 ℃ scope inner drying, the order by backing protective layer, drug storehouse layer, controlled release rete, adhesion layer and antiseized protective layer after viscosity is suitable is combined with each other, and it is square to be die-cut into 10CM2; Both get transdermal patch, contained 4% povidone iodine, 1% fluticasone propionate.
Embodiment 6
The preparation of PVP-I (5%) fluticasone propionate (1%) liniment
| Component | Consumption (gram) |
| Fluticasone propionate | 2.4 |
| Povidone iodine | 12 |
| Potassium iodate | 0.0072 |
| Hydroxyethyl-cellulose | 10 |
| Sodium chloride | 4 |
| Tween 80 | 1.2 |
| Camphora | 1.44 |
| Oleum Caryophylli | 1.68 |
| Boric acid | 72 |
Method for preparing:
The fully even matter of Tween 80 that in the 100g sterilized water, adds micronized fluticasone propionate of 2.4g and recipe quantity successively adds hydroxyethyl-cellulose, sodium chloride, Camphora, boric acid, Oleum Caryophylli and pure water more than 12 hours again, forms suspensoid.With 12 the gram povidone iodine dry powder, potassium iodate, be dissolved in this suspending agent.Add about 2000mL water in irrigator bottle, add sodium hydroxide and regulate pH value to 4.0,, make to contain 5%PVP-I in the suspensoid solution, contain 1% fluticasone propionate quantitatively to 2400 grams.
Embodiment 7
The preparation of PVP-I (0.2%) halometasone (0.01%) compound recipe suspensoid
| Material | Consumption (gram) |
| Halometasone | 0.24 |
| Povidone iodine | 4.8 |
| Hydroxyethyl-cellulose | 10 |
| Potassium iodate | 0.072 |
| Sodium chloride | 4 |
| Thyrode husky primary | 0.4 |
| EDTA-Na | 0.3 |
Method for preparing is with reference to embodiment 1.
Embodiment 8
The preparation of PVP-I (0.5%) halometasone (0.05%) ointment
| Component | Consumption (gram) |
| Halometasone | 0.12 |
| Povidone iodine | 1.2 |
| Hexadecanol | 2 |
| Sodium lauryl sulphate | 2.1 |
| White vaseline | 33.5 |
| Liquid paraffin | 13.5 |
| Glycerol | 11.2 |
| Potassium iodate | 0.0072 |
| Stearic acid | 9 |
| Glyceryl monostearate | 8 |
| Water | 160 |
| Tween 80 | 0.084 |
| EDTA-Na | 0.025 |
Method for preparing is with reference to embodiment 2 operations.
Embodiment 9
The preparation of PVP-I (1%) halometasone (0.5%) gel
| Component | Consumption (gram) |
| Halometasone | 1.2 |
| Povidone iodine | 2.4 |
| Potassium iodate | 0.0072 |
| Carbopol 941 | 1 |
| Sodium chloride | 0.4 |
| Poloxamer | 0.8 |
| EDTA-Na | 0.023 |
Method for preparing is with reference to embodiment 3.
Embodiment 10
The preparation of PVP-I (2%) halometasone (1%) spray
| Component | Consumption (gram) |
| Halometasone | 2.4 |
| Povidone iodine | 4.8 |
| Potassium iodate | 0.0072 |
| Ai Wei plain 591 | 1.5 |
| Sodium chloride | 0.4 |
| PEG4000 | 1.2 |
| EDTA-Na | 0.025 |
Method for preparing is with reference to embodiment 4.
Embodiment 11
The preparation of PVP-I (4%) halometasone (1%) transdermal patch
| Component (drug storehouse layer) | Consumption (gram) |
| Halometasone | 1.85 |
| Povidone iodine | 7.4 |
| Potassium iodate | 0.0048 |
| Polyacrylic resin | 11.7 |
| Ethyl acetate | 5.6 |
| Lauryl alcohol | 0.93 |
| Lecithin | 0.93 |
| Component (adhesion layer) | Consumption (gram) |
| Halometasone | 0.55 |
| Povidone iodine | 2.2 |
| Potassium iodate | 0.0016 |
| Polyacrylic resin | 12.1 |
| Ethyl acetate | 5.87 |
| Lauryl alcohol | 0.93 |
| Lecithin | 0.27 |
Method for preparing is with reference to embodiment 5.
Embodiment 12
The preparation of PVP-I (5%) halometasone (1%) liniment
| Component | Consumption (gram) |
| Halometasone | 2.4 |
| Povidone iodine | 12 |
| Potassium iodate | 0.0072 |
| Hydroxyethyl-cellulose | 10 |
| Sodium chloride | 4 |
| Tween 80 | 1.16 |
| Camphora | 1.44 |
| Oleum Caryophylli | 1.68 |
| Boric acid | 72 |
Method for preparing is with reference to embodiment 6.
Claims (7)
1. pharmaceutical composition that prevents and/or treats scytitis; It is characterized in that: in the pharmaceutical composition gross weight; Povidone iodine by 0.01%～5%, 0.01%～10% glucocorticoid, 0.001%～0.5% potassium iodate and the pharmaceutically acceptable carrier of surplus are formed; Wherein glucocorticoid is fluticasone propionate or halometasone, all is weight percentage.
2. the pharmaceutical composition of claim 1, wherein povidone iodine content is 0.01%～2%, fluticasone propionate or halometasone content are 0.01%～2%.
3. the pharmaceutical composition of claim 1, wherein povidone iodine content is 0.01%～1%, fluticasone propionate or halometasone content are 0.01%～1%.
4. the pharmaceutical composition of claim 1, wherein fluticasone propionate or halometasone carry out the compositions preparation again behind micronization.
5. the pharmaceutical composition of claim 1, its dosage form is ointment, ointment, gel, suspensoid, spray, transdermal patch or liniment.
6. the pharmaceutical composition of claim 1, wherein pharmaceutically acceptable carrier is selected from one or more in pH regulator agent, surfactant, viscosity modifier, suspending agent, oil phase, rheology control agent, consistency modifiers, emulsifying agent, wetting agent, stabilizing agent, osmotic pressure regulator, complexing of metal ion agent, the water.
7. the pharmaceutical composition of claim 1 is used to prepare the purposes of the medicine that prevents and/or treats scytitis.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102514190A CN102379893A (en) | 2011-08-29 | 2011-08-29 | Compound pharmaceutical composition of iodine polymer and glucocorticosteroid for treating dermatitis |
| PCT/CN2012/080656 WO2013029525A1 (en) | 2011-08-29 | 2012-08-28 | Pharmaceutical composition comprising iodine polymer and glucocorticosteroid for treating dermatitis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102514190A CN102379893A (en) | 2011-08-29 | 2011-08-29 | Compound pharmaceutical composition of iodine polymer and glucocorticosteroid for treating dermatitis |
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| CN2011102514190A Pending CN102379893A (en) | 2011-08-29 | 2011-08-29 | Compound pharmaceutical composition of iodine polymer and glucocorticosteroid for treating dermatitis |
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| Country | Link |
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| WO (1) | WO2013029525A1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102727426A (en) * | 2012-07-25 | 2012-10-17 | 中国药科大学 | Emulsifiable paste for treating non-infectious inflammatory dermatosis and method for preparing emulsifiable paste |
| WO2013029525A1 (en) * | 2011-08-29 | 2013-03-07 | 江苏德达医药科技有限公司 | Pharmaceutical composition comprising iodine polymer and glucocorticosteroid for treating dermatitis |
| CN103110976A (en) * | 2012-12-20 | 2013-05-22 | 贵州扬生医用器材有限公司 | Skin antimicrobial gel recipe and preparation method thereof |
| CN103127138A (en) * | 2011-12-01 | 2013-06-05 | 重庆华邦制药有限公司 | Halometasone preparation containing protective agent and preparation method thereof |
| CN107519180A (en) * | 2016-06-20 | 2017-12-29 | 天津金耀集团有限公司 | Dermopharmaceutical composition using Halometasone as active component |
| CN113439904A (en) * | 2021-06-29 | 2021-09-28 | 苏州宣医智慧医疗科技有限公司 | Jacket for wet bag treatment of skin diseases |
| CN115887421A (en) * | 2022-11-25 | 2023-04-04 | 上海市第一人民医院 | Compound glucocorticoid film spraying agent and preparation and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101693038A (en) * | 2008-10-17 | 2010-04-14 | 吴霜 | Pharmaceutical composition for treating skin (A) disease |
| CN102078611A (en) * | 2009-11-26 | 2011-06-01 | 天津金耀集团有限公司 | Partial external use composition containing povidone Iodine and cyclodextrin inclusion glucocorticoid |
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| CN1203864C (en) * | 2003-07-23 | 2005-06-01 | 南京大学 | Spray formulation of providone iodine |
| US7767217B2 (en) * | 2006-03-14 | 2010-08-03 | Foresight Biotherapeutics | Ophthalmic compositions comprising povidone-iodine |
| CN102379893A (en) * | 2011-08-29 | 2012-03-21 | 江苏德达医药科技有限公司 | Compound pharmaceutical composition of iodine polymer and glucocorticosteroid for treating dermatitis |
-
2011
- 2011-08-29 CN CN2011102514190A patent/CN102379893A/en active Pending
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- 2012-08-28 WO PCT/CN2012/080656 patent/WO2013029525A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101693038A (en) * | 2008-10-17 | 2010-04-14 | 吴霜 | Pharmaceutical composition for treating skin (A) disease |
| CN102078611A (en) * | 2009-11-26 | 2011-06-01 | 天津金耀集团有限公司 | Partial external use composition containing povidone Iodine and cyclodextrin inclusion glucocorticoid |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013029525A1 (en) * | 2011-08-29 | 2013-03-07 | 江苏德达医药科技有限公司 | Pharmaceutical composition comprising iodine polymer and glucocorticosteroid for treating dermatitis |
| CN103127138A (en) * | 2011-12-01 | 2013-06-05 | 重庆华邦制药有限公司 | Halometasone preparation containing protective agent and preparation method thereof |
| CN103127138B (en) * | 2011-12-01 | 2017-08-04 | 重庆华邦制药有限公司 | Contain protectant Halometasone preparation and preparation method thereof |
| CN102727426A (en) * | 2012-07-25 | 2012-10-17 | 中国药科大学 | Emulsifiable paste for treating non-infectious inflammatory dermatosis and method for preparing emulsifiable paste |
| CN103110976A (en) * | 2012-12-20 | 2013-05-22 | 贵州扬生医用器材有限公司 | Skin antimicrobial gel recipe and preparation method thereof |
| CN107519180A (en) * | 2016-06-20 | 2017-12-29 | 天津金耀集团有限公司 | Dermopharmaceutical composition using Halometasone as active component |
| CN113439904A (en) * | 2021-06-29 | 2021-09-28 | 苏州宣医智慧医疗科技有限公司 | Jacket for wet bag treatment of skin diseases |
| CN115887421A (en) * | 2022-11-25 | 2023-04-04 | 上海市第一人民医院 | Compound glucocorticoid film spraying agent and preparation and application thereof |
| CN115887421B (en) * | 2022-11-25 | 2024-03-29 | 上海市第一人民医院 | Compound glucocorticoid spray film agent and preparation and application thereof |
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| Publication number | Publication date |
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| WO2013029525A1 (en) | 2013-03-07 |
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Application publication date: 20120321 |