CN105012297A - Use of indole-3-carbinol, bis-indolymethane and derivatives thereof in drugs for treatment on contact dermatitis - Google Patents
Use of indole-3-carbinol, bis-indolymethane and derivatives thereof in drugs for treatment on contact dermatitis Download PDFInfo
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Abstract
The invention provides a use of indole-3-carbinol, bis-indolymethane and derivatives thereof in drugs for treatment on contact dermatitis. Indole-3-carbinol, bis-indolymethane and derivatives thereof can inhibit basal cell mitosis and thus they can treat contact dermatitis. DIM and I3C and derivatives thereof can effectively reduce contact dermatitis symptoms and can be used as drug molecule candidates for treating contact dermatitis. The used micromolecular drugs can be acquired easily, a price is low, properties are stable, preservation and transport are convenient and a wide application prospect is obtained.
Description
Technical field
The invention belongs to biomedicine technical field, be used for the treatment of the application of contact dermatitis medicine more specifically to Indole-3-carbinol, di-indole methyl hydride and derivant thereof.
Background technology
Contact dermatitis refers to every phenomenon causing skin to produce inflammation allergy because touching material, can be referred to as contact dermatitis, common are the dermatitis, metal allergy, cosmetic skin inflammation etc. that paste Chinese medicine and cause.In pathogenesis, different T cell subgroups and the cytokine of secretion play a part very important, are in particular in that the I cytokines of secretion increases, and T cell is towards Th1 type differentiation skew.Wherein the presenting and lymphocytic propagation and differentiation of I cytokines IFN-γ scalable antigen, the antigen presentation efficiency of enhancement antigen presenting cells, is the factor of macrophage of the most effectively lighting a fire, regulates synthesis and the secretion of panimmunity active medium.And II cytokines IL-4 can suppress the morbidity of contact dermatitis, after systematicness application IL-4, long inflammation protective effect can be played to local skin.
Summary of the invention
The object of the present invention is to provide a kind of disease symptom effectively can treating contact dermatitis animal model, can be used as the application at the medicine for the treatment of contact dermatitis of the treatment molecule drug candidate of contact dermatitis and Indole-3-carbinol, di-indole methyl hydride and derivant thereof.
Indole-3-carbinol and the application of derivant in preparation treatment contact dermatitis medicine thereof with structural formula (I) of the present invention, in structural formula (I), R1, R2, R4, R5, R6, R7 are H or halogenic substituent or nitro or C1-C10 alkyl or C1-C10 alkoxyl separately.
Preferably, in described structural formula (I), when R1, R2, R4, R5, R6, R7 are hydrogen, the compound shown in this structural formula is Indole-3-carbinol;
When R5 is halogenic substituent or nitro or C1-C10 alkyl or C1-C10 alkoxyl, R1, R2, R4, R6, R7 are hydrogen, now, the compound shown in this structural formula (I) comprises: the chloro-Indole-3-carbinol of 5-, the bromo-Indole-3-carbinol of 5-, the fluoro-Indole-3-carbinol of 5-; 5-nitro-indole-3-methanol; 5-Methvl-indole-3-methanol, 5-Ethyl-indole-3-methanol, 5-propyl group-Indole-3-carbinol, 5-butyl-Indole-3-carbinol, 5-amyl group-Indole-3-carbinol, 5-Methoxv-indole-3-methanol, 5-ethyoxyl-Indole-3-carbinol, 5-propoxyl group-Indole-3-carbinol, 5-butoxy-Indole-3-carbinol, 5-amoxy-Indole-3-carbinol etc.;
When R1 is C1-C10 alkyl or C1-C10 alkoxyl, R2, R4, R5, R6, R7 are hydrogen, now, the compound shown in this structural formula (I) comprises: N-Methvl-indole-3-methanol, N-Ethyl-indole-3-methanol, N-propyl group-Indole-3-carbinol, N-butyl-Indole-3-carbinol, N-amyl group-Indole-3-carbinol, N-Methoxv-indole-3-methanol, N-ethyoxyl-Indole-3-carbinol, N-propoxyl group-Indole-3-carbinol, N-butoxy-Indole-3-carbinol, N-amoxy-Indole-3-carbinol etc.;
When R2 is C1-C10 alkyl or C1-C10 alkoxyl, R1, R4, R5, R6, R7 are hydrogen, now, the compound shown in this structural formula (I) comprises: 2-Methvl-indole-3-methanol, 2-Ethyl-indole-3-methanol, 2-propyl group-Indole-3-carbinol, 2-butyl-Indole-3-carbinol, 2-amyl group-Indole-3-carbinol, 2-Methoxv-indole-3-methanol, 2-ethyoxyl-Indole-3-carbinol, 2-propoxyl group-Indole-3-carbinol, 2-butoxy-Indole-3-carbinol, 2-amoxy-Indole-3-carbinol etc.;
Di-indole methyl hydride and the application of derivant in preparation treatment contact dermatitis medicine thereof with structural formula (II) of the present invention,
Wherein, R1, R2, R4, R5, R6, R7, R1 ', R2 ', R4 ', R5 ', R6 ', R7 ' are separately hydrogen or halogen substituent group or nitro or C1-C10 alkyl or C1-C10 alkoxyl.
Preferably, in described structural formula (II), as R1, R2, R4, R5, R6, R7, R1 ', R2 ', R4 ', R5 ', R6 ', R7 ' be when being hydrogen, now the compound shown in this structural formula is di-indole methyl hydride;
When R5 and R5 ' is halogenic substituent or nitro or C1-C10 alkyl or C1-C10 alkoxyl simultaneously, R1, R2, R4, R6, R7, R1 ', R2 ', R4 ', R6 ', R7 ' be hydrogen, now, shown in structural formula (II), compound comprises: 5,5 '-two chloro-di-indole methyl hydride, 5,5 '-two bromo-di-indole methyl hydride or 5,5 '-two fluoro-di-indole methyl hydride; 5,5 '-dinitro-di-indole methyl hydride; 5,5 '-dimethyl-di-indole methyl hydride, 5,5 '-diethyl-di-indole methyl hydride, 5,5 '-dipropyl-di-indole methyl hydride, 5,5 '-dibutyl-di-indole methyl hydride, 5,5 '-diamyl-di-indole methyl hydride, 5,5 '-dimethoxy-di-indole methyl hydride, 5,5 '-diethoxy-di-indole methyl hydride, 5,5 '-dipropoxy-di-indole methyl hydride, 5,5 '-dibutoxy-di-indole methyl hydride or 5,5 '-two amoxy-di-indole methyl hydride etc.
When R1 and R1 ' is C1-C10 alkyl or C1-C10 alkoxyl simultaneously, R2, R4, R5, R6, R7, R2 ', R4 ', R5 ', R6 ', R7 ' be hydrogen, now, shown in structural formula (II), compound comprises: N, N '-dimethyl-di-indole methyl hydride, N, N '-diethyl-di-indole methyl hydride, N, N '-dipropyl-di-indole methyl hydride, N, N '-dibutyl-di-indole methyl hydride, N, N '-diamyl-di-indole methyl hydride.N, N '-dimethoxy-di-indole methyl hydride, N, N '-diethoxy-di-indole methyl hydride, N, N '-dipropoxy-di-indole methyl hydride, N, N '-dibutoxy-di-indole methyl hydride or N, N '-two amoxy-di-indole methyl hydride etc.
When R2 and R2 ' is C1-C10 alkyl or C1-C10 alkoxyl simultaneously, R1, R4, R5, R6, R7, R1 ', R4 ', R5 ', R6 ', R7 ' is hydrogen, now, shown in structural formula (II), compound comprises: 2, 2 '-dimethyl-di-indole methyl hydride, 2, 2 '-diethyl-di-indole methyl hydride, 2, 2 '-dipropyl-di-indole methyl hydride, 2, 2 '-dibutyl-di-indole methyl hydride, 2, 2 '-diamyl-di-indole methyl hydride, 2, 2 '-dimethoxy-di-indole methyl hydride, 2, 2 '-diethoxy-di-indole methyl hydride, 2, 2 '-dipropoxy-di-indole methyl hydride, 2, 2 '-dibutoxy-di-indole methyl hydride or 2, 2 '-two amoxy-di-indole methyl hydride etc.
Indole-3-carbinol of the present invention, di-indole methyl hydride and derivant thereof are in the application for the treatment of contact dermatitis medicine, single compound Indole-3-carbinol or a kind of use of di-indole methyl hydride or derivatives thereof can treat contact dermatitis, so obvious, the various forms of mixtures of above-claimed cpd also can reach certain therapeutic effect.
Use commercial available substituted indoles may be obtain these compounds method the most easily to synthesize the substitutive derivative of I3C.The derivant of DIM can be prepared by the method for formaldehyde condensation substituted indoles equally.But the inferior position of the latter is that the formation of by-product makes the DIM derivant required for separation and purification more complicated.
Compound provided by the present invention is the indole-3-acetaldehyde replaced by using dimethyl formamide condensation substituted indoles to synthesize preparation, and the indole-3-acetaldehyde product be substituted reduces its aldehyde radical thus obtain the substitutive derivative of I3C by use methanol and sodium borohydride process.Indole-3-carbinol (I3C) is very unstable in gastric acid environment in vivo, condensation reaction can occur and form oligomer 3,3'-Diindolylmethane.The substitutive derivative of di-indole methyl hydride of the present invention (DIM) is synthesized by the substitution product of condensation Indole-3-carbinol (I3C), and this can realize (the derivant preparation of I3C and DIM is with reference to US Patent No. 5948808) by taking the methods such as the phosphate buffer process of such as pH value about 5.5.
Adopt Indole-3-carbinol of the present invention (I3C), di-indole methyl hydride (DIM) and derivant thereof, combine with multiple pharmaceutically acceptable carrier, by such as oral cavity, vein, nasal cavity, rectum or other any administering modes can carrying the active substance of effective dose, various liquid preparation can be prepared into as injection, oral liquid formulations etc., also can be prepared into various effectively and the solid preparation being easy to administration as capsule, suppository etc.Wherein, for injecting or liquid preparation for oral use, the carrier needed for it can be the carrier as medically acceptable in cyclodextrin, Semen Maydis oil, olive oil, ethyl oleate, glycols etc. of sterilized water, Sterile Saline or water solublity organic carrier; Solid dosage formulation can add the conventional adjuvant of solid preparation as excipient glucose, lactose, cellulose etc. in preparation, also can add lubricant Polyethylene Glycol, magnesium stearate etc., and the adjunct ingredient needed for the solid preparation such as binding agent, correctives, then by operation molding such as mixing, granulations.The effective dose of the active substance in these preparations above-mentioned is the amount that contact dermatitis symptom can be made obviously to reduce, the research worker with routine techniques can determine that the most effective dosage of the reagent that this invention provides and time consider administering mode, drug metabolism, and some other pharmacokinetic parameter such as drug distribution, clearance rate etc.
The present invention carries out illustration by model of contact dermatitis.Animal herein includes, but are not limited to: mice, rat, and performing animal includes, but are not limited to cat, Canis familiaris L., and some other animal is such as still not limited to cattle, sheep, pig, horse, and primate is such as still not limited to monkey and people.
The present invention proposes the application at treatment contact dermatitis medicine of Indole-3-carbinol, di-indole methyl hydride and derivant thereof.
Find in animal experiment, DIM and I3C and derivative compound thereof effectively can reduce the disease symptom of contact dermatitis animal model, the molecule drug candidate for the treatment of contact dermatitis can be become, can significantly inflammation-inhibiting allergy and to T cell differentiation adjustment, especially to the adjustment of Th1 cell, and then the object for the treatment of contact dermatitis is reached.Meanwhile, small-molecule drug used in the present invention is easy to obtain, and cheap, stable in properties, is convenient to storage and transport, has broad application prospects.
Detailed description of the invention
Be clearly and completely described the technical scheme in the embodiment of the present invention below in conjunction with the embodiment of the present invention, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
[compound preparation]
Embodiment 1
(5-chloro-indole-3-methanol and 5, the preparation of 5 '-dichloro di-indole methyl hydride)
0.86ml phosphoryl chloride phosphorus oxychloride is slowly joined 2.9ml be cooled in advance in the dimethyl formamide of 0 DEG C.8.6mmol 5-chloro-indole (being purchased from Nanjing R&M Fine Chemical Co., Ltd.) is dissolved in the dimethyl formamide of 1.0ml, then slowly add in the phosphoryl chloride phosphorus oxychloride solution of aforementioned pre-cooling, the suspension formed was 37 DEG C of heating 60 minutes, until the yellow solution of clarification becomes flaxen pasty mass.Then in this pasty mass, add the frozen water of 1ml, more slowly add the aqueous solution that 10ml contains 3.75 grams of KOH.Be heated to boil rear cooling by this mixture, filter, washing, air drying can obtain 5-chloro-indole-3-acetaldehyde.
1.0 grams of 5-chloro-indole-3-acetaldehyde are dissolved in 5.0ml methanol, continue to add solid sodium borohydride, until excessive.Then in reactant, add 50ml water, be cooled to 0 DEG C, filter, lucifuge vacuum drying obtains 5-chloro-indole-3-methanol, yield about 90%.
It is in the phosphate buffer of 5.5 that 1.0 grams of 5-chloro-indole-3-methanol are joined pH, stirring at room temperature 6 hours, and course of reaction is monitored by thin layer chromatography (TLC).Product is filtered, and namely lucifuge vacuum drying obtains 5,5 '-dichloro di-indole methyl hydride, yield about 85%.
Embodiment 2
(5-nitroindoline-3-methanol and 5, the preparation of 5 '-dinitro di-indole methyl hydride)
5-nitroindoline can be bought by business and obtain (Nanjing R&M Fine Chemical Co., Ltd.).0.92ml phosphoryl chloride phosphorus oxychloride is slowly joined 2.9ml be cooled in advance in the dimethyl formamide of 0 DEG C.Be dissolved in the dimethyl formamide of 1.0ml by 8.2mmol5-nitroindoline, then slowly add in the phosphoryl chloride phosphorus oxychloride solution of aforementioned pre-cooling, the suspension formed was 42 DEG C of heating 90 minutes, until the yellow solution of clarification becomes flaxen pasty mass.Then in this pasty mass, add the frozen water of 1ml, more slowly add the aqueous solution that 10ml contains 3.75 grams of KOH.Be heated to boil rear cooling by this mixture, filter, washing, air drying can obtain 5-nitroindoline-3-acetaldehyde.
1.0 grams of 5-nitroindoline-3-acetaldehyde are dissolved in 5.0ml methanol, continue to add solid sodium borohydride, until excessive.Then in reactant, add 50ml water, be cooled to 0 DEG C, filter, lucifuge vacuum drying obtains 5-nitroindoline-3-methanol, yield about 87%.
It is in the phosphate buffer of 5.5 that 1.0 grams of 5-nitroindoline-3-methanol are joined pH, stirring at room temperature 6 hours, and course of reaction is monitored by thin layer chromatography (TLC).Product is filtered, and namely lucifuge vacuum drying obtains 5,5 '-dinitro bis (indolyl) methane, yield about 80%.
Embodiment 3
(5-amyl group Indole-3-carbinol and 5, the preparation of 5 '-diamyl-di-indole methyl hydride)
5-amyl group indole can be bought by business and obtain (Nanjing R&M Fine Chemical Co., Ltd.).0.82ml phosphoryl chloride phosphorus oxychloride is slowly joined 2.9ml be cooled in advance in the dimethyl formamide of 0 DEG C.Be dissolved in the dimethyl formamide of 1.0ml by 9.2mmol5-amyl group indole, then slowly add in the phosphoryl chloride phosphorus oxychloride solution of aforementioned pre-cooling, the suspension formed heats 40-60 minute at 37 DEG C, until the yellow solution of clarification becomes flaxen pasty mass.Then in this pasty mass, add the frozen water of 1ml, more slowly add the aqueous solution that 10ml contains 3.75 grams of KOH.Be heated to boil rear cooling by this mixture, filter, washing, air drying can obtain 5-amyl group indole-3-acetaldehyde.
1.0 grams of 5-amyl group indole-3-acetaldehyde are dissolved in 5.0ml methanol, continue to add solid sodium borohydride, until excessive.Then in reactant, add 50ml water, be cooled to 0 DEG C, filter, lucifuge vacuum drying obtains 5-amyl group Indole-3-carbinol, yield about 85%.
It is in the phosphate buffer of 5.5 that 1.0 grams of 5-amyl group Indole-3-carbinols are joined pH, stirring at room temperature 10 hours, and course of reaction is monitored by thin layer chromatography (TLC).Product is filtered, and namely lucifuge vacuum drying obtains 5,5 '-diamyl bis (indolyl) methane, yield about 70%.
Embodiment 4
The preparation of-dimethoxy-di-indole methyl hydride (N-methoxy-Indole-3-methanol and N, the N ')
N-methoxy-Indole can be bought by business and obtain (Nanjing R&M Fine Chemical Co., Ltd.).0.86ml phosphoryl chloride phosphorus oxychloride is slowly joined 2.9ml be cooled in advance in the dimethyl formamide of 0 DEG C.Be dissolved in the dimethyl formamide of 1.0ml by 8.9mmolN-methoxy-Indole, then slowly add in the phosphoryl chloride phosphorus oxychloride solution of aforementioned pre-cooling, the suspension formed heats 60-90 minute at 40 DEG C, until the yellow solution of clarification becomes flaxen pasty mass.Then in this pasty mass, add the frozen water of 1ml, more slowly add the aqueous solution that 10ml contains 3.75 grams of KOH.Be heated to boil rear cooling by this mixture, filter, washing, air drying can obtain N-methoxy-Indole-3-acetaldehyde.
1.0 grams of N-methoxy-Indole-3-acetaldehyde are dissolved in 5.0ml methanol, continue to add solid sodium borohydride, until excessive.Then in reactant, add 50ml water, be cooled to 0 DEG C, filter, lucifuge vacuum drying obtains N-methoxy-Indole-3-methanol, yield about 80%.
It is in the phosphate buffer of 5.5 that 1.0 grams of N-methoxy-Indole-3-methanol are joined pH, stirring at room temperature 12 hours, and course of reaction is monitored by thin layer chromatography (TLC).Product is filtered, and namely lucifuge vacuum drying obtains N, N '-dimethoxy bis (indolyl) methane, yield about 70%.
Embodiment 5
(1-butyl-2 methyl indole-3-methanol and 1, the preparation of 1 '-dibutyl-2,2 '-dimethyl di-indole methyl hydride)
1-butyl-2 methyl indole can be bought by business and obtain (Nanjing R&M Fine Chemical Co., Ltd.).0.82ml phosphoryl chloride phosphorus oxychloride is slowly joined 2.9ml be cooled in advance in the dimethyl formamide of 0 DEG C.8.2mmol 1-butyl-2 methyl indole is dissolved in the dimethyl formamide of 1.0ml, then slowly add in the phosphoryl chloride phosphorus oxychloride solution of aforementioned pre-cooling, the suspension formed was 42 DEG C of heating 90 minutes, until the yellow solution of clarification becomes flaxen pasty mass.Then in this pasty mass, add the frozen water of 1ml, more slowly add the aqueous solution that 10ml contains 3.8 grams of KOH.Be heated to boil rear cooling by this mixture, filter, washing, air drying can obtain 1-butyl-2 methyl indole-3-acetaldehyde.
1.0 grams of 1-butyl-2 methyl indole-3-acetaldehyde is dissolved in 5.0ml methanol, continues to add solid sodium borohydride, until excessive.Then in reactant, add 50ml water, be cooled to 0 DEG C, filter, lucifuge vacuum drying obtains 1-butyl-2 methyl indole-3-methanol, yield about 85%.
It is in the phosphate buffer of 5.5 that 1.0 grams of 1-butyl-2 methyl indole-3-methanol is joined pH, stirring at room temperature 6 hours, and course of reaction is monitored by thin layer chromatography (TLC).Product is filtered, and namely lucifuge vacuum drying obtains 1,1 '-dibutyl-2,2 '-dimethyl bis (indolyl) methane, yield about 80%.
Embodiment 6
(4-bromo indole-3-methanol and 4, the preparation of 4 '-dibromo di-indole methyl hydride)
0.86ml phosphoryl chloride phosphorus oxychloride is slowly joined 2.9ml be cooled in advance in the dimethyl formamide of 0 DEG C.8.6mmol 4-bromo indole (being purchased from Nanjing R&M Fine Chemical Co., Ltd.) is dissolved in the dimethyl formamide of 1.0ml, then slowly add in the phosphoryl chloride phosphorus oxychloride solution of aforementioned pre-cooling, the suspension formed was 37 DEG C of heating 60 minutes, until the yellow solution of clarification becomes flaxen pasty mass.Then in this pasty mass, add the frozen water of 1ml, more slowly add the aqueous solution that 10ml contains 3.75 grams of KOH.Be heated to boil rear cooling by this mixture, filter, washing, air drying can obtain 4-bromo indole-3-acetaldehyde.
1.0 grams of 4-bromo indole-3-acetaldehyde are dissolved in 5.0ml methanol, continue to add solid sodium borohydride, until excessive.Then in reactant, add 50ml water, be cooled to 0 DEG C, filter, lucifuge vacuum drying obtains 4-bromo indole-3-methanol, yield about 90%.
It is in the phosphate buffer of 5.5 that 1.0 grams of 4-bromo indole-3-methanol are joined pH, stirring at room temperature 6 hours, and course of reaction is monitored by thin layer chromatography (TLC).Product is filtered, and namely lucifuge vacuum drying obtains 4,4 '-dibromo di-indole methyl hydride, yield about 85%.
[zoopery]
Material
Respectively by I3C, DIM, the chloro-Indole-3-carbinol of 5-(5-Cl-I3C), 5,5 '-two chloro-di-indole methyl hydride (5,5 '-Cl-DIM), 5-amyl group-Indole-3-carbinol (5-C5-I3C), 5,5 '-diamyl-di-indole methyl hydride (5,5 '-C5-DIM), 5-Methoxv-indole-3-methanol (5-MOE-I3C), 5,5 '-dimethoxy-di-indole methyl hydride (5,5 '-MOE-DIM), 5-nitro-indole-3-methanol (5-NO-I3C), 5,5 '-dinitro-di-indole methyl hydride (5,5 '-NO-DIM), N-Methvl-indole-3-methanol (N-Me-I3C), N, N '-dimethyl-di-indole methyl hydride (N, N '-Me-DIM), N-Methoxv-indole-3-methanol (N-MOE-I3C), N, N '-dimethoxy-di-indole methyl hydride (N, N '-MOE-DIM), 2-amyl group-Indole-3-carbinol (2-C5-I3C), 2,2 '-diamyl-di-indole methyl hydride (2,2 '-C5-DIM), 2-Methoxv-indole-3-methanol (2-MOE-I3C), 2,2 '-dimethoxy-di-indole methyl hydride (2,2 '-MOE-DIM), 1-butyl-2-Methvl-indole-3-methanol (1Bu-2Me-I3C), 1,1 '-dibutyl-2,2 '-dimethyl-di-indole methyl hydride (1,1 ' Bu-2,2 ' Me-DIM), it is for subsequent use that the bromo-Indole-3-carbinol of 4-(4-Br-I3C) and 4,4 '-two bromo-di-indole methyl hydride (4,4 '-Br-DIM) are made into the oral liquid storage of 2.0mg/ml with Semen Maydis oil dissolving.
Experimental technique
By BALB/c SPF level male mice, 10 ~ 12 week age body weight 20 ~ 23g, mice 230, is divided into 23 groups and often organizes 10, is divided into model control group at random and uses I3C respectively, DIM, the chloro-Indole-3-carbinol of 5-(5-Cl-I3C), 5,5 '-two chloro-di-indole methyl hydride (5,5 '-Cl-DIM), 5-amyl group-Indole-3-carbinol (5-C5-I3C), 5,5 '-diamyl-di-indole methyl hydride (5,5 '-C5-DIM), 5-Methoxv-indole-3-methanol (5-MOE-I3C), 5,5 '-dimethoxy-di-indole methyl hydride (5,5 '-MOE-DIM), 5-nitro-indole-3-methanol (5-NO-I3C), 5,5 '-dinitro-di-indole methyl hydride (5,5 '-NO-DIM), N-Methvl-indole-3-methanol (N-Me-I3C), N, N '-dimethyl-di-indole methyl hydride (N, N '-Me-DIM), N-Methoxv-indole-3-methanol (N-MOE-I3C), N, N '-dimethoxy-di-indole methyl hydride (N, N '-MOE-DIM), 2-amyl group-Indole-3-carbinol (2-C5-I3C), 2,2 '-diamyl-di-indole methyl hydride (2,2 '-C5-DIM), 2-Methoxv-indole-3-methanol (2-MOE-I3C), 2,2 '-dimethoxy-di-indole methyl hydride (2,2 '-MOE-DIM), 1-butyl-2-Methvl-indole-3-methanol (1Bu-2Me-I3C), 1,1 '-dibutyl-2,2 '-dimethyl-di-indole methyl hydride (1,1 ' Bu-2,2 ' Me-DIM), the treatment group that the bromo-Indole-3-carbinol of 4-(4-Br-I3C) and 4,4 '-two bromo-di-indole methyl hydride (4,4 '-Br-DIM) are treated.
Mice is for testing first 1 day in abdominal part unhairing, and area is about 3cm
2experimental day and next day, each sensitization of 25 μ l once in unhairing position coating 0.5%DNFB (DNFB with 4:1 acetone olive oil for substrate configures), within after sensitization the 5th day, bring out dermatitis in mice left ear backside 0.5%DNFB20 μ l, auris dextra is coated with equivalent acetone olive oil substrate and compares.
Medication is: except model control group gavages normal saline, and all the other are respectively organized within the 0th, 1,2,5 day, to bring out front 2h respectively at experiment respectively and bring out rear 6h and gavage corresponding oral liquid storage 20mg/kg.d.
Detection method
Method 1: under etherization measure the thickness in the middle part of mouse ear with outside micrometer before and after bringing out, the piece of tissue in the middle part of ear is got with the card punch of diameter 0.8mm, analytical balance is weighed, calculate the quality of left and right ear block, calculate thickness and weight difference meansigma methods that mice left and right ear brings out front and back, the results are shown in Table 1:
Experimental result shows: treatment group mouse ear inflammation swelling degree comparatively model group compares obviously reduction and P<0.05, comprise weight and the thickness of ear, therefore the state of an illness has the symptom significantly slowing down symptom, illustrates that Indole-3-carbinol, di-indole methyl hydride and derivant thereof have certain curative effect to slowing down and treating dermatitis symptom.
Method 2: after measurement terminates, mice is plucked eyeball and get blood, 2h is prevented under room temperature, 2000r/min centrifugalize serum,-20 DEG C frozen, finally survey every suction shading value with putting microplate reader 450nm wavelength place, with IFN-γ and IL-4 standard concentration and to OD value (answering hole average) set up recurrence and hold high into, drawing standard curve, and try to achieve the content meansigma methods of IFN-γ and IL-4 in each mice serum according to this, refer to following table 2.
Table 2
| Group | IFN-γ(pg/ml) | IL-4(pg/ml) |
| Model control group | 212.63 | 24.66 |
| I3C | 121.89 | 17.56 |
| DIM | 109.06 | 16.04 |
| 5-Cl-I3C | 113.14 | 16.84 |
| 5,5’-Cl-DIM | 114.24 | 16.79 |
| 5-C5-I3C | 117.70 | 17.24 |
| 5,5’-C5-DIM | 115.63 | 17.12 |
| 5-MOE-I3C | 115.01 | 16.97 |
| 5,5’-MOE-DIM | 114.90 | 17.01 |
| 5-NO-I3C | 116.41 | 16.98 |
| 5,5’-NO-DIM | 115.68 | 16.84 |
| N-Me-I3C | 109.87 | 16.45 |
| N,N’-Me-DIM | 109.97 | 16.89 |
| N-MOE-I3C | 109.92 | 16.78 |
| N,N’-MOE-DIM | 111.45 | 17.02 |
| 2-C5-I3C | 119.4 | 17.32 |
| 2,2’-C5-DIM | 117.35 | 17.11 |
| 2-MOE-I3C | 116.44 | 17.22 |
| 2,2’-MOE-DIM | 118.76 | 17.39 |
| 1Bu-2Me-I3C | 112.23 | 16.79 |
| 1,1’Bu-2,2’Me-DIM | 114.34 | 16.54 |
| 4-Br-I3C | 115.76 | 16.55 |
| 4,4’-Br-DIM | 116.34 | 16.98 |
As can be seen from experimental data, each treatment group IFN-γ obviously reduces (P<0.05) compared with model control group, and IL-4 expresses also reduction (P<0.05).
In this experiment, Indole-3-carbinol, di-indole methyl hydride and derivant thereof have good curative effect for the contingency contact dermatitis of mice, not only obviously alleviate the swelling degree of mouse ear and oozing out of local organization liquid, show good anti-IV type allergy active.And Indole-3-carbinol, di-indole methyl hydride and derivant thereof effectively can lower the IFN-γ of mice in the present embodiment, also there is downward effect to II cytokines IL-4 simultaneously, illustrate that this compound can promote that T cell is to the differentiation of Th2 type, reaches the effect for the treatment of contingency contact dermatitis.
Claims (8)
1. have following structural formula (I) for the application of Indole-3-carbinol at treatment contact dermatitis medicine,
Wherein, R1 is hydrogen or C1-C10 alkyl or C1-C10 alkoxyl; R2 is hydrogen or C1-C10 alkyl or C1-C10 alkoxyl; R5 is hydrogen or halogen substituent group or nitro; R4, R6, R7 are hydrogen.
2. Indole-3-carbinol according to claim 1 is in the application for the treatment of contact dermatitis medicine, it is characterized in that: in described structure formula I, R5 is halogenic substituent or nitro, and R1, R2, R4, R6, R7 are hydrogen.
3. Indole-3-carbinol according to claim 1 is in the application for the treatment of contact dermatitis medicine, and it is characterized in that: in described structure formula I, R1 is C1-C10 alkyl or C1-C10 alkoxyl, and R2, R4, R5, R6, R7 are hydrogen.
4. Indole-3-carbinol according to claim 1 is in the application for the treatment of contact dermatitis medicine, and it is characterized in that: in described structure formula I, R2 is C1-C10 alkyl or C1-C10 alkoxyl, and R1, R4, R5, R6, R7 are hydrogen.
5. there is the application of di-indole methyl hydride at treatment contact dermatitis medicine of following structural formula (II),
Wherein, R1 and R1 ' is hydrogen or C1-C10 alkyl or C1-C10 alkoxyl; R2 and R2 ' is hydrogen or C1-C10 alkyl or C1-C10 alkoxyl; R5 and R5 ' is hydrogen or halogen substituent group or nitro; R4, R6, R7, R4 ', R6 ', R7 ' be hydrogen.
6. di-indole methyl hydride according to claim 5 is in the application for the treatment of contact dermatitis medicine, it is characterized in that: in described structure formula II, R5 and R5 ' is halogenic substituent or nitro simultaneously, R1, R2, R4, R6, R7, R1 ', R2 ', R4 ', R6 ', R7 ' be hydrogen.
7. di-indole methyl hydride according to claim 5 is in the application for the treatment of contact dermatitis medicine, it is characterized in that: in described structure formula II, R1 and R1 ' is C1-C10 alkyl or C1-C10 alkoxyl simultaneously, R2, R4, R5, R6, R7, R2 ', R4 ', R5 ', R6 ', R7 ' be hydrogen.
8. di-indole methyl hydride according to claim 5 is in the application for the treatment of contact dermatitis medicine, it is characterized in that: in described structure formula II, R2 and R2 ' is C1-C10 alkyl or C1-C10 alkoxyl simultaneously, R1, R4, R5, R6, R7, R1 ', R4 ', R5 ', R6 ', R7 ' be hydrogen.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344564A (en) * | 2016-08-11 | 2017-01-25 | 安徽四正医药科技有限公司 | Application of indole-3-carbinol and diindolylmethane and derivatives thereof in preparation of medicines for treating hair follicle keratosis |
| KR20230106223A (en) * | 2022-01-06 | 2023-07-13 | 영남대학교 산학협력단 | Composition for inhibiting biofilm formation and antibacterial against Gram-positive bacteria and fungi comprising indole derivatives |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102389419A (en) * | 2011-10-08 | 2012-03-28 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolylmethane and derivatives thereof to preparation of medicine for preventing and controlling atherosclerosis |
-
2015
- 2015-06-24 CN CN201510355014.XA patent/CN105012297A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102389419A (en) * | 2011-10-08 | 2012-03-28 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolylmethane and derivatives thereof to preparation of medicine for preventing and controlling atherosclerosis |
Non-Patent Citations (2)
| Title |
|---|
| AGNIESZKA GE˛GOTEK ET AL.: "The role of transcription factor Nrf2 in skin cells metabolism.", 《ARCH DERMATOL RES》 * |
| CONSTANCE LAY‐LAY SAW ET AL.: "Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates.", 《BIOPHARM. DRUG DISPOS》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344564A (en) * | 2016-08-11 | 2017-01-25 | 安徽四正医药科技有限公司 | Application of indole-3-carbinol and diindolylmethane and derivatives thereof in preparation of medicines for treating hair follicle keratosis |
| KR20230106223A (en) * | 2022-01-06 | 2023-07-13 | 영남대학교 산학협력단 | Composition for inhibiting biofilm formation and antibacterial against Gram-positive bacteria and fungi comprising indole derivatives |
| KR102670270B1 (en) * | 2022-01-06 | 2024-05-28 | 영남대학교 산학협력단 | Composition for inhibiting biofilm formation and antibacterial against Gram-positive bacteria and fungi comprising indole derivatives |
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