CN101953836A - Application of fluoropirfenidone in preparing medicaments for treating psoriasis - Google Patents
Application of fluoropirfenidone in preparing medicaments for treating psoriasis Download PDFInfo
- Publication number
- CN101953836A CN101953836A CN 201010253460 CN201010253460A CN101953836A CN 101953836 A CN101953836 A CN 101953836A CN 201010253460 CN201010253460 CN 201010253460 CN 201010253460 A CN201010253460 A CN 201010253460A CN 101953836 A CN101953836 A CN 101953836A
- Authority
- CN
- China
- Prior art keywords
- application
- akf
- psoriasis
- medicine
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to new pharmaceutical application of fluoropirfenidone, in particular to the application of fluoropirfenidone in preparing medicaments for treating the psoriasis. When the fluoropirfenidone is used for treating the psoriasis, the fluoropirfenidone is administrated in a local and external form.
Description
Technical field
The present invention relates to treat psoriatic new drug: particularly, the present invention relates to the new medicinal approach of Fluorofenidone.More specifically, the present invention relates to the application of Fluorofenidone in the psoriatic medicine of preparation treatment.
Background technology
Psoriasis (psoriasis) is commonly called as " psoriasis ", and its course of disease is indefinite, and chronic alleviation alternately occurs with deterioration often.Be divided into four types clinically, i.e. homeliness type, pustule type, arthrosis type and erythrodermic, wherein homeliness type accounts for more than 90%.Clinical manifestation is to be covered with silvery white squama on skin erythema, pimple or the patch, and pruritus in various degree can be arranged.Psoriatic pathological characteristic mainly is that hyper-proliferative, disdifferentiation and the intradermal inflammatory cell infiltration of epidermal keratinocytes (KC) is obvious.Present treatment means is more, but therapeutic effect is unsatisfactory.Treatment psoriasis common drug has: ciclosporin, methotrexate, corticosteroid hormone, tar class, retinoic acid, tazarotene, camptothecine, Triptolide etc., but the medicine of many took orally for treating psoriasis has stronger side effect, as ciclosporin systematic treating psoriasis untoward reaction such as nephrotoxicity, hypertension, malignant tumor, infection are arranged, Radix Tripterygii Wilfordii oral medication psoriasis has digestive tract side reaction and influential to cardiovascular system and liver.Psoriasis is the pathological changes of skin immune system, and external preparation can reduce the untoward reaction of system, therefore, should strengthen psoriatic's external treatment.For local transdermal delivery system in the external treatment, it is relevant that the ratio of curative effect of medication and untoward reaction and its intensity and percutaneous absorb, we wish medicine seldom through skin and high amount of drug should be accumulated in the skin target site.
The psoriatic cause of disease and pathogenesis are not clear and definite as yet, since the nineties in 20th century, the onset of psoriasis Study on Mechanism has been obtained important breakthrough, and people recognize that gradually psoriasis is the cell-mediated dysimmunity disease of T under the multifactor effects such as polygenic inheritance background and context.Wherein, the Th1 cell is to psoriatic morbidity and continue that facilitation is arranged, and the Th2 cell has and the opposite effect of Th1 cell.Psoriatic characteristics are excessively increments of keratinocyte (KC), and parakeratosis is soaked into multiple inflammatory cell and cytokine, and keratinocyte can be secreted the various kinds of cell factor and participate in the local immunity reaction.Wherein, Th1 and Tc cell, the place is activated at skin lesion, produce IFN-γ, TNF, IL-2, cytokines such as IL 1, and IFN-γ and TNF are main two cytokines that cause that the horn cell psoriasis changes, and cause that the horn cell hyperplasia produces psoriasis typical case skin lesion and changes.Short epidermis proliferating cells factor research is more in recent years, as epidermal growth factor (EGF), keratinocyte growth factor (KGF), transforming growth factor one α (TGF-α) etc., but does not obtain very ideal results as the target treatment.Wherein keratinocyte growth factor (KGF) is to have the synthetic somatomedin of the keratinocyte DNA of promotion, produce by fibroblasts to secrete, (Putmins EE plays an important role in psoriatic pathogenesis, Firth JD, Lohachitranont A.et al.Ke-ratinocyte growth factor (KGF) promotes keratinocyte cell attachment and migr-ation or collagen andfibronectine[J] .Cell Adhes Common 1999,7 (3): 211-221).Discover and transform growth because of β 1 (transforming growth factor, TGF-β 1) high expressed can work in coordination with or induce other molecule to promote psoriatic development (Li A.G., Wang D., Feng X.H.Latent TGF-β 1overexpression inkeratinocytes results in a severe psoriasis-1ike skin disorder[J] .The EMBOJournal (2004), 23,1770-1781).TGF-β 1 has the multi-functional cytokine of a class of regulating cell growth, differentiation, produce by inflammatory infiltration cell and keratinocyte, the epidermis that is present in the people, (extracellular matrix ECM) plays a significant role in the processes such as the reconstruction of formation, bone, immunomodulating at wound healing, fetal development, extracellular matrix.(Kane CJ is increased in TGF-β 1 expression that studies show that the normal skin of psoriatic lesions skin part, Knapp AM, Mansbridge JN et al.Transforming growth factor-beta 1 localization in normal andpsoriasis epidermal keratinocytes in situ[J] .J Cell Physiol, 1990,144,144-150), and psoriasis peripheral blood TGF-β 1 level obviously raises, with psoriasis area and severity index (PASI) positive correlation (Kallimanis P.G., Xenos K., Markantonis L.S.et al.Serum levels of transforminggrowth factor-β 1 in patients with mild psoriasis vulgaris and effect of treatmentwith biological drugs[J] (ahead of print) .Clin Dermatol, DOI:10.1111/j.1365-2230.2008.03026.x).TGF-β 1 expresses in psoriatic tissue may be influenced with the weight situation of skin injury, its concentration and age in tissue and serum, sex and disease persistent period (the H Zaher that has nothing to do, 0G Shaker, et a1.Serum and tissue expression of transforming growth factor beta1 in psoriasis[J] .ORIGINAL ARTICLE.DOI:10.1111/j.1468-3083.2008.03064.x)
Fluorofenidone (fluorofenidone, AKF-PD) be a kind of novel anti fibrosis micromolecular compound, chemistry 1-(substituted-phenyl) by name-5-methyl-2-(1H) pyridone, the meto medicine for pirfenidone (pirfenidone) has the pharmacotoxicological effect similar with pirfenidone.Pirfenidone is that patent CN1386737A discloses pyridinone medicine production process by the new anti-fibrosis medicine of U.S. Marnac company development.Experiment in vitro confirms that this chemical compound has the excitement etc. that suppresses to cause expression such as fibrosis factor TGF-β 1, PDGF, precollagen I and III is expressed descend, promotes collagen degradation, is suppressed to fibrocellular breeding and response cytokine thereof and acts on (Shigeki S, Murakami T, Yata N, eta1.Treatment of keloid and hypertrophic scars by iontophoretic transdermal deli-very of tranilast.Scand J Plast Reconstr Surg Hand Surg, 1997,31 (2): 151-158.).
Although it is inhibited to various ECM (extracellular matrix) generation cell that patent CN1846699A discloses Fluorofenidone (AKF-PD), can suppress mice mesangial cell, rat heart muscle fibroblast, people's hepatic stellate cell, induced lung fibroblast, application on human skin cicatrix fibrocyte, people's peritoneal mesothelium cel l proliferation, the result shows that AKF-PD can be used as the active component of the anti-organ or tissue of preparation fibrosis medicine, and toxic and side effects is little, drug safety.Patent CN101371833A discloses the application of 1-aryl-2 (1H) pyridine compounds in preparation treatment skin pruritus medicine.The pirfenidone that CN1775212A discloses with the Fluorofenidone similar is used for the treatment of psoriasic application, implements with the form of oral or topical application.PCT application CN2008/072406 has announced the application of Fluorofenidone as antitumor drug, is used for the treatment of pulmonary carcinoma, breast carcinoma, colon cancer, gastric cancer, hepatocarcinoma and carcinoma of prostate.Yet, up to the present, Fluorofenidone (AKF-PD) is not used for the treatment of psoriatic report as yet.
Summary of the invention:
The purpose of this invention is to provide the psoriatic new drug of a kind of treatment, i.e. the new purposes of known compound Fluorofenidone.
The invention provides the application of Fluorofenidone (AKF-PD) in preparation treatment psoriasis medicine.
When being used for the treatment of psoriasis, main mechanism is to suppress the high expressed of the TGF-β 1 in the psoriatic lesions skin with Fluorofenidone (AKF-PD).
The present invention also provides Fluorofenidone (AKF-PD) when the psoriasis medicine is treated in preparation, the preparation that is adopted can be the external preparation of this area routine, can be ointment, gel, patch, suspensoid or Emulsion etc., medicine can be present in ointment, gel, patch, suspensoid or the Emulsion with forms such as solid lipid nanoparticle, nanometer liposome, microemulsion, solid dispersion.
No matter use which kind of dosage form, the concentration of Fluorofenidone (AKF-PD) should be at about 0.5%-10% (wt/wt), each about 5-15mg of amount of application, every day 1-3 time.
Embodiment
Further specify the present invention below by specific embodiments.Described embodiment only is used for explanation or explains embodiment of the present invention, and can not limit protection scope of the present invention.
Embodiment 1 Fluorofenidone (AKF-PD) ointment
The composition consumption
AKF-PD 0.5g
MCT 4.0g
Octadecanol 2.0g
Stearic acid 2.0g
Glyceryl monostearate 0.4g
Azone 0.5g
Tween-80 0.6g
1,2-propylene glycol 2.0g
Glycerol 1.0g
Water 10.0g
Ethyl hydroxybenzoate alcoholic solution 100 μ L/23g
Preparation method
1. take by weighing oil phase and water by recipe quantity respectively.Wherein AKF-PD, MCT, octadecanol, stearic acid, glyceryl monostearate, azone be as oil phase, Tween-80,1, and 2-propylene glycol, glycerol, water, ethyl hydroxybenzoate alcoholic solution are as water.
2. oil phase, water are dissolved in 75 ℃ of water-baths respectively.
3. under 75 ℃ of water-bath magnetic agitation, water is slowly poured in the oil phase, stirs 1min.
4. change in the 50mL centrifuge tube, at the rate of shear down cut 3min of 3600rpm.
5. centrifuge tube is placed 20 ℃ of psychrolusia coolings promptly to get the ointment of level and smooth uniform and smooth.
As required, wherein AKF-PD content can be regulated between 0.5%-10%.
Embodiment 2 Fluorofenidones (AKF-PD) gel
The composition consumption
AKF-PD 0.5g
1,2-propylene glycol 17.5g
Ethyl hydroxybenzoate ethanol liquid (0.1mg/100 μ L) 10mg/100 μ L
Carbopol?940 0.25g
Glycerol 1.0g
Triethanolamine is an amount of
Water 7.5g
Preparation method
1. the Carbopol 940 that takes by weighing recipe quantity is soaked in water, and makes its abundant swelling.
2. in joining glycerol 1., stir evenly, as A.
3. get the AKF-PD of recipe quantity, 1, the 2-propylene glycol, ethyl hydroxybenzoate ethanol liquid is dissolved to clarification in 60 ℃ of water-baths, as B.
4. pour B into A, stir evenly, drip triethanolamine and transfer pH to 6.0, become clear and bright gel promptly.
Similarly, according to the conventional method of this area,, can prepare the preparation of the various topical application that contain Fluorofenidone (AKF-PD), as cream, lotion, patch, suspensoid or Emulsion etc. by carrier that is applicable to the local topical preparation and/or excipient.
Embodiment 3 AKF-PD gels
The composition consumption
AKF-PD 0.1g
1,2-propylene glycol 1.0g
Isopropyl alcohol 1.0g
Ethyl hydroxybenzoate 0.01g
Carbopol?940 0.25g
Triethanolamine is an amount of
Water 3.0g
Operating procedure:
1. the Carbopol 940 that takes by weighing recipe quantity is soaked in water, and makes its abundant swelling, and is standby.
2. get the AKF-PD, 1 of recipe quantity, 2-propylene glycol, isopropyl alcohol, ethyl hydroxybenzoate are dissolved to clarification in 60 ℃ of water-baths.
2. what 3. will prepare pours among the good Carbopol of swelling 940, stirs evenly.
4. drip triethanolamine and transfer pH to 6.0, become clear and bright gel promptly.
Embodiment 4AKF-PD Emulsion
The composition consumption
AKF-PD 0.5g
Soybean oil 1.5g
Phosphatidase 10 .5g
Gelatin 0.02g
Glycerol 0.4g
Ethylene glycol 0.4g
Organosilicon 0.06g
Water 7.0g
Operating procedure:
1. the gelatin of getting recipe quantity makes its abundant swelling with 1.0g water logging bubble, and is standby.
2. get AKF-PD, soybean oil, phospholipid mixed dissolution in 60 ℃ of water-baths of recipe quantity, as oil phase.
3. glycerol, ethylene glycol, gelatin solution and the organosilicon with recipe quantity under agitation is added to the water successively, constantly stirs until being dissolved into uniform liquid, as water.
4. under the high speed shear emulsification instrument, water is slowly joined oil phase, shear rate is 10000rpm, shears 6 minutes, obtains the opaque Emulsion of milky.
Embodiment 5 AKF-PD emulsion agents
The composition consumption
AKF-PD 0.1g
Oleic acid 0.2g
Tween 80 0.04g
Carbopol?940 0.25g
Ethyl hydroxybenzoate 0.02g
Triethanolamine is an amount of
Glycerol 0.2g
Water 3.0g
Operating procedure:
1. the Carbopol 940 that takes by weighing recipe quantity is soaked in water, and makes its abundant swelling, and is standby.
2. get AKF-PD, oleic acid, tween 80 mixed dissolution in 60 ℃ of water-baths of recipe quantity, as oil phase.
3. with ethyl hydroxybenzoate, glycerol, water mixed dissolution in 60 ℃ of water-baths of recipe quantity, as water.
4. under the high speed shear emulsification instrument, water is slowly joined oil phase, shear rate is 10000rpm, shears 6 minutes, obtains the opaque Emulsion of milky.
5. above-mentioned Emulsion is joined among the good Carbopol of swelling 940, stir evenly, drip triethanolamine and transfer pH to 6.0, promptly get clear gel.
6. the above-mentioned Emulsion for preparing in is 4. joined in the gel, mixing, promptly.
Embodiment 6 AKF-PD treat psoriatic animal model experiment
Mus tail scale lacks granular layer because of the normal keratinization of epidermis, and its natural keratinization forms similar to human psoriasis epidermis, so can simulate the Parakeratotic characteristics of psoriasis.Utilize this model can estimate the effect that medicine promotes that granular layer forms, think that medicine if can promote Mus tail granular layer to form, and then may have function of resisting psoriasis.
Concrete operations: get 40 of ICR mices, male and female half and half, body weight 25～30g is divided into 5 groups at random, 10 every group.The administration group is: three dosage AKF-PD ointment groups, the blank ointment group of dosage.Each is organized and smears mouse tail every day 2 times (0.2g
-1D
-1).Continuous use 14 days, last are smeared the back and are put to death animal next day, get epidermis at distance Mus root of the tail portion 2cm place.Carry out the conventional organization section, HE dyeing.Light microscopic is observed down, and the scale epidermis between all two hair follicles has the granular cell layer person who embarks on journey continuously, is called the scale that has granular layer to form.Count the scale number (the scale epidermis between all two follicular orifices has the granular layer person who is arranged in rows to count the scale that granular layer forms) that granular layer is arranged in per 100 scales, respectively organize data.Experimental result sees Table 1.
The influence that table 1 various dose AKF-PD ointment forms mouse tail scale granular layer of epidermis
Annotate: with blank ointment group contrast,
*P＜0.01
The result shows, 2%-10%AKF-PD ointment group is compared with blank ointment group, P＜0.05, statistical significance is arranged, the AKF-PD ointment that is various dose is compared the effect that Mus tail scale granular layer of epidermis forms with blank ointment base the effect that Mus tail scale granular layer of epidermis forms, and difference has significance.Prompting AKF-PD is formed with obvious facilitation to Mus tail scale granular layer of epidermis, and the scale digital display work of granular layer increases.Therefore, AKF-PD can change the keratinization degree of epidermis, returns to normal keratinization from parakeratosis, and then psoriasis is had therapeutical effect.
Embodiment 7 general naphthalene Nores bring out psoriasis model
Get 50 Cavia porcelluss, male and female half and half are divided into 5 groups at random, i.e. normal control group, blank ointment group and three dosage AKF-PD ointment groups, and except that the normal control group, all the other each groups are coated with the Propranolol liniment in left side auricle (0.3g/cm with cotton swab
2), 2 times/d, continuous 2 weeks are to cause ear skin silver bits sample skin lesion model.After this begin medication, the not medication of normal control group, (0.2g/ d "); after 2 weeks of medication gets the Guinea Pig Left wide skin of picking up the ears, and fixes; paraffin embedding HE dyeing, variations such as observation skin of pinna horny layer, granular layer, prickle cell layer, basal cell layer with 10% formalin in all the other group administrations every day 2 times.(* 400) survey epidermal thickness with micrometer under light microscopic simultaneously, are converted into actual (real) thickness (μ m) then, carry out each group difference relatively.Experimental result sees Table 2.
Table 2 various dose AKF-PD brings out the influence of psoriasis model to general naphthalene Nore
Annotate: compare with blank ointment group
*P＜0.05
The result shows, 2%-10%AKF-PD ointment group is compared with blank ointment group, P＜0.05, statistical significance is arranged, be that various dose AKF-PD ointment is compared with blank ointment the effect that epidermis thickens, difference has significance, and prompting AKF-PD has thickened obvious facilitation to epidermis, that is to say that AKF-PD has therapeutical effect to the psoriasis model that general naphthalene Nore brings out.
Embodiment 8 AKF-PD Ointment in Treatment are suffered from psoriasis volunteer's effect
The result shows: suffer from psoriasis with the AKF-PD Ointment in Treatment, remarkable result is arranged.
Claims (6)
1. the application of Fluorofenidone in the psoriatic medicine of preparation treatment.
2. according to the application of claim 1, wherein said medicine is the medicine of local topical.
3. according to the application of claim 2, the medicine of wherein said local topical comprises ointment, gel, patch Emulsion, suspensoid or lotion.
4. according to the application of claim 3, form such as medicine can solid lipid nanoparticle, nanometer liposome, microemulsion, solid dispersion is present in ointment, gel, patch, Emulsion, suspensoid or the lotion.
5. according to the application of claim 3, wherein said preparation of Chinese medicine concentration is 0.5%-10% (wt/wt)., generally use 1.0%-5.0%.
6. according to the described application of claim 5, wherein each about 5-15mg of amount of application, every day 1-3 time.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010253460 CN101953836A (en) | 2010-08-13 | 2010-08-13 | Application of fluoropirfenidone in preparing medicaments for treating psoriasis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010253460 CN101953836A (en) | 2010-08-13 | 2010-08-13 | Application of fluoropirfenidone in preparing medicaments for treating psoriasis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101953836A true CN101953836A (en) | 2011-01-26 |
Family
ID=43481595
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010253460 Pending CN101953836A (en) | 2010-08-13 | 2010-08-13 | Application of fluoropirfenidone in preparing medicaments for treating psoriasis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101953836A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113274389A (en) * | 2021-07-09 | 2021-08-20 | 中南大学 | Application of flufenidone in preparation of medicine for treating acute lung injury |
| CN113456636A (en) * | 2021-07-09 | 2021-10-01 | 中南大学 | Application of flufenidone in preparation of acute liver injury medicine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1775212A (en) * | 2004-11-16 | 2006-05-24 | 徐旗开 | Use of pirfenidone for treating psoriasis |
-
2010
- 2010-08-13 CN CN 201010253460 patent/CN101953836A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1775212A (en) * | 2004-11-16 | 2006-05-24 | 徐旗开 | Use of pirfenidone for treating psoriasis |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113274389A (en) * | 2021-07-09 | 2021-08-20 | 中南大学 | Application of flufenidone in preparation of medicine for treating acute lung injury |
| CN113456636A (en) * | 2021-07-09 | 2021-10-01 | 中南大学 | Application of flufenidone in preparation of acute liver injury medicine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7037205B2 (en) | Uses for suppressing or ameliorating itching of compositions containing stem cell-derived exosomes as an active ingredient | |
| RU2533458C2 (en) | Compositions containing berberine or its analogues for treating skin diseases related to rosacea or blush | |
| CN109125107B (en) | Polypeptide composition for effectively improving and repairing facial hormone-dependent dermatitis | |
| KR102045188B1 (en) | A composition comprising an exosome derived from adipose-derived stem cell as an active ingredient and its application for improving dermatitis | |
| CN113855718A (en) | Artemisia apiacea extract and application thereof | |
| CN102421428B (en) | Composition for preventing hair loss or for stimulating hair growth | |
| CN112587593B (en) | Composition for treating acne and preparation method thereof | |
| CN101953836A (en) | Application of fluoropirfenidone in preparing medicaments for treating psoriasis | |
| CN105963243B (en) | A kind of borneol cinnamomum camphora essential oil sustained release emulsifiable paste and preparation method thereof for treating acne vulgaris | |
| JPH10120579A (en) | Skin preparation for improving sputum for external use | |
| JPH10175868A (en) | Water (of chinese medicine idea) improving composition | |
| US20070286915A1 (en) | Nerve Growth Factor Production Inhibitor and External Preparation for the Skin, Cosmetic, Quasi Drug, Preventive and Remedy for Atopic Dermatitis Containing the Nerve Growth Factor Production Inhibitor | |
| KR102368646B1 (en) | Atopy treatment lotion utilizing room temperature emulsifying process | |
| JPH10120558A (en) | Skin preparation for improving sputum for external use | |
| CN102872158A (en) | External drug combination for curing eczema and preparation method thereof | |
| CN108451952B (en) | A composition for treating skin immunological diseases and its preparation method | |
| CN104784627A (en) | Traditional Chinese medicine externally used film agent used for treatment surgical open or closed injury and preparation method thereof | |
| CN100389799C (en) | Tibetan medicine for relieving pain and its preparing method | |
| JP2022517983A (en) | A pharmaceutical composition for the prevention or treatment of atopic dermatitis containing clonal stem cells. | |
| CN105878427A (en) | Peony seed oil compound spray for curing burn and scald and preparation method | |
| US11607438B2 (en) | Topical cream-based cosmetic and wound healing formulations and methods of use | |
| CN103463309B (en) | One treats psoriatic pharmaceutical composition | |
| US20230201296A1 (en) | Topical cream-based cosmetic and wound healing formulations and methods of use | |
| CN103463308B (en) | The application of tea polyphenols stearate and one treat psoriatic pharmaceutical composition | |
| KR20240073357A (en) | Composition for treating atopic dermatitis comprising exosomes derived from canine mesenchymal stem cells pretreated with IFN-γ |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20110126 |