CN101380293A - 10-acetyl-dithranol hydrogel and preparation method thereof - Google Patents
10-acetyl-dithranol hydrogel and preparation method thereof Download PDFInfo
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- CN101380293A CN101380293A CNA2008101403470A CN200810140347A CN101380293A CN 101380293 A CN101380293 A CN 101380293A CN A2008101403470 A CNA2008101403470 A CN A2008101403470A CN 200810140347 A CN200810140347 A CN 200810140347A CN 101380293 A CN101380293 A CN 101380293A
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Abstract
The invention discloses a 10-acetyl dithranol hydrogel and a preparation method thereof. The hydrogel is prepared from the raw materials by weight proportion as follows: 3g-23.7g of 10-acetyl dithranol, 17g-23g of salicylic acid, 120g-160g of glycerol, 8g-12g of carbomer-940, 0.5g-1.5g of ethyl hydroxy benzoate, 7ml-12ml of triethanolamine, 0.5g -1.5g of ascorbic acid, 3ml-7ml of ethanol, 0.5ml-1.5ml of essence and 700ml-850ml of purified water. The 10-acetyl dithranol hydrogel has the advantages of inhibiting the proliferation of epidermal cells by reducing DNA synthesis, inhibiting the respiration of mitochondrion, recovering relevant enzyme in skin lesion caused by psoriasis, and inhibiting the functions of monocytes. As the increasing concentration therapy is adopted, the drug stays at the skin lesion for 24 hours; when the transient touch therapy is adopted, the irritation can be reduced.
Description
Technical field
The present invention relates to medicine, is a kind of 10-acetyl dithranol hydrogel adhesive and preparation method thereof.
Background technology
Existing anti-psoriasis medicine for external use mainly comprises following a few class: potent glucocorticoid, vitamin D
3Derivant, tar class, dithranol water and tretinoin.Though said medicine is effective, have following shortcoming: the glucocorticoid external can cause the local skin atrophy, and telangiectasis, folliculitis etc., large-area applications also may cause whole body to absorb and the side effect of the system of generation, even makes state of an illness aggravation; The tar class causes the patient and is difficult to accept owing to its inherent abnormal flavour and greasy dirt can not get effectively overcoming; Vitamin D
3Derivant is domestic still can not produce, dependence on import, and costing an arm and a leg is difficult to promote; Tretinoin medicines has obvious skin irritation.
Dithranol (Dithranol) chemical name 1,8-dihydroxy-9-anthrone, 1916 are first-selected synthetic by Galowsky, and being used for the treatment of psoriasis vulgaris has had nearly 90 years history.Dithranol water is strong reductant, has anti-epidermal cell proliferation, induces epithelial cell differentiation, anti-inflammatory effect, and it treats the psoriatic main mechanism of action the following aspects: 1, by reducing the synthetic epidermal cell proliferation that suppresses of DNA; 2, suppress mitochondrial Repiration; 3, make in the psoriatic lesion relevant enzyme recover normal; 4, suppress monocytic function.Dithranol water does not have accumulating of system's toxic and side effects with sure, cheap, the prolonged and repeated application of its curative effect and is subjected to dermatologist's favor, remains a line medicine of treatment psoriasis vulgaris at present in Europe.But dithranol water has obvious stimulation to normal skin, can cause erythema, burn feeling, edema, vesicle, pain appear in severe patient, and can make skin and medicated clothing dye yellowish-brown and be difficult to removes, so applying, it is restricted, the dermatologist of the U.S. seldom uses dithranol water now, is exactly because so.Many in recent years scholars improve the dithranol hydrotherapy, have proposed progressive concentration therapy, of short duration contact therapy, drug combination therapy and package treatment.In addition, in the preparation of dithranol water, also improve, developed dithranol water rod wax, developed the dithranol water of liposome and microencapsulation, stimulate the problem that causes untoward reaction but still can not fundamentally solve dithranol water.
Domestic and international many scholars have carried out the research of seeking dithranol water derivant since the 1980s, discovery adds side chain at dithranol water chemistry structure C-10, can prevent that not only it is oxidized to dimer, increase stability, and can reduce its stimulation, but side chain is long more, and its therapeutical effect is weak more.The foreign scholar has synthesized the derivant of multiple dithranol water, and wherein the research of relevant 10-butyryl dithranol water is a lot of, and other derivants are because therapeutical effect is more weak and superseded.Discover that 10-butyryl dithranol water does not have tangible chafe and painted side effect, and curative effect anthrol water closely, basic research shows that 10-butyryl dithranol water has with like the dithranol water and acts on, but up to the present also do not have the report of 10-butyryl dithranol water formulation as the new drug listing.
Summary of the invention
The purpose of this invention is to provide a kind of 10-acetyl dithranol hydrogel adhesive and preparation method thereof, 10-acetyl dithranol is made into a kind of psoriatic medicine for external use of treatment ectype of evident in efficacy, few side effects.
The present invention for achieving the above object, be achieved through the following technical solutions: 10-acetyl dithranol hydrogel adhesive, its raw material of making the weight ratio of gel comprises: 10-acetyl dithranol 3g-23.7g, salicylic acid 17g-23g, glycerol 120g-160g, carbomer-9408g-12g, ethyl hydroxybenzoate 0.5g-1.5g, triethanolamine 7ml-12ml, ascorbic acid 0.5g-1.5g, ethanol 3ml-7ml, essence 0.5ml-1.5ml, purified water 700ml-850ml.Described 10-acetyl dithranol hydrogel adhesive, its raw material of making the weight ratio of gel comprises: 10-acetyl dithranol 11g, salicylic acid 20g, glycerol 150g, carbomer-94010g, ethyl hydroxybenzoate 1g, triethanolamine 10ml, ascorbic acid 0.5g, ethanol 5ml, essence 1ml, purified water 800ml.The preparation method of described 10-acetyl dithranol hydrogel adhesive, get the dithranol raw material and heavily steam benzene and place the three neck reaction bulbs of putting into ice-water bath, stir, make dithranol be dissolved in the benzene as far as possible, when the question response liquid temp is reduced to 7 ℃ ± 1 ℃, add and heavily steam anhydrous pyridine, behind the stir about 2 minutes, slowly add chloroacetic chloride, stirring reaction adds distilled water and washs approximately after 30 minutes, mixed liquor is put in the separatory funnel, leave standstill a moment, isolate upper strata liquid, add anhydrous sodium sulfate, shake well, the back is after the lucifuge place places dry 1.5 hours, put into rotary evaporator, addend grain zeolite, water-bath is concentrated into approximately, placement is spent the night and is caused the product crystallization and separate out fully, get carbomer-94010g and add the 700ml purified water and place 24hr, abundant swelling is after the 10-acetyl dithranol and the salicylic acid fine powder 20g that crosses 80 mesh sieves of recipe quantity added 150g glycerol and grind well, add in good carbomer-940 substrate of swelling, stir, again with ethyl hydroxybenzoate 1g, ascorbic acid 0.5g and essence 1ml add in the 5ml ethanol after the dissolving, add in the substrate that contains principal agent to stir, add triethanolamine 10ml at last and regulate pH value between 6～7, remaining purified water is added to full dose, stir evenly, packing, promptly.
Beneficial effect of the present invention is: selected patients with psoriasis vulgaris 42 examples are participated in this research, complete data person 32 examples, wherein male 19 examples, women 13 examples, age 18-65 year, average 37 years old, course of disease June-30 year, average course of disease 9 years has 23 examples to increase the weight of winters, have 2 examples to increase the weight of summer, 7 examples are not obvious season.Skin lesion scalp 25 examples of getting involved, upper limb 18 examples of getting involved, trunk 32 examples of getting involved, lower limb 22 examples of getting involved, skin lesion branch all has obvious symmetry.
In the 32 routine patients that finish, dithranol hydrogel adhesive 8 examples that are almost recovered for 4 weekends, produce effects 18 examples, progressive 6 examples, invalid 0 example, the rate of being almost recovered are 25%, effective percentage is 81.25%.10-acetyl dithranol hydrogel adhesive 6 examples that are almost recovered, produce effects 17 examples, progressive 8 examples, invalid 1 example, the rate of being almost recovered are 18.75%, effective percentage is 71.88%.Compare 10-acetyl dithranol hydrogel adhesive and the dithranol hydrogel adhesive difference (p〉0.05) that is almost recovered rate and effective percentage there are no significant with the μ of two sample rates check.The stimulation index of 10-acetyl dithranol hydrogel adhesive and dithranol hydrogel gel and Di are all less than dithranol hydrogel gel (p＜0.05).Advantage of the present invention also comprises: by reducing the synthetic epidermal cell proliferation that suppresses of DNA; Suppress mitochondrial Repiration; Make in the psoriatic lesion and just recovering about enzyme; Suppress monocytic function.
The present invention's symmetric patients with psoriasis vulgaris of progressive concentration therapy for treating 32 routine skin lesion, observation through 4 weeks, confirm that 10-acetyl dithranol hydrogel treatment psoriasis is effective, with dithranol hydrogel therapeutic equivalence, and stimulation and painted side effect obviously are less than the dithranol hydrogel under same molar ratio.Its gel dosage form is cleaned easily, and less pollution clothes is welcome by the patient more than dithranol hydrogel.10-acetyl dithranol hydrogel more is applicable to the of short duration therapy that contacts with the dithranol aqueogel in theory.Because what the present invention adopted is the progressive concentration therapy, reservation reaches 24 hours to medicine at the skin lesion place, if adopt of short duration contact therapy, can reduce both zests.
The specific embodiment
Embodiment:
10-acetyl dithranol hydrogel adhesive of the present invention, its raw material of making the weight ratio of gel comprises:
1,10-acetyl dithranol 3g, salicylic acid 17g, glycerol 120g, carbomer-9408g, ethyl hydroxybenzoate 0.5g triethanolamine 7ml, ascorbic acid 0.5g, ethanol 3ml, essence 0.5ml, purified water 700ml.
2,10-acetyl dithranol 23.7g, salicylic acid 23g, glycerol 160g, carbomer-94012g, ethyl hydroxybenzoate 1.5g, triethanolamine 12ml, ascorbic acid 1.5g, ethanol 7ml, essence 1.5ml, purified water 850ml.
3,10-acetyl dithranol 11g, salicylic acid 20g, glycerol 150g, carbomer-94010g, ethyl hydroxybenzoate 1g, triethanolamine 10ml, ascorbic acid 0.5g, ethanol 5ml, essence 1ml, purified water 800ml.
Preparation method of the present invention: dithranol raw material: benzene; Pyridine; Chloroacetic chloride; Anhydrous sodium sulfate; Distilled water; Glacial acetic acid; Sodium metal; Potassium hydroxide.Experimental apparatus: counter balance, three neck reaction flasks, single neck distilling flask, graduated cylinder, common funnel, separatory funnel, buchner funnel, filter paper, bottle,suction, spherical condensation tube, catcher, zeolite, thermometer, the iron stand of band test tube clamp, magnetic stirring apparatus, stirrer, electric jacket, water-bath, Rotary Evaporators, sucking filtration machine, refrigerator, the experimental implementation cabinet that performance of ventilating is good.Chemical equation is as follows:
The pretreatment of chemical reagent: the redistillation of benzene: it is an amount of to get benzene, put in single neck distilling flask, add zeolite number, put into thermometer, connect condensing tube and distillate catcher, single neck distilling flask is put into water-bath, regulate bath temperature to higher 2～3 ℃ than the boiling point of benzene, the speed controlling of distillate is about 60 of per minutes, after catcher cleans with an amount of distillate, collect distillate, liquid in the flask to be distilled stops heating when also remaining 20～30ml left and right sides, puts to room temperature, and distillate is poured into cleaning, in the anhydrous Brown Glass Brown glass bottles and jars only, add behind an amount of sodium metal airtightly, shading is preserved standby.The redistillation of pyridine: it is an amount of to get pyridine, put in single neck distilling flask, add zeolite number, put into thermometer, connect condensing tube and distillate catcher, single neck distilling flask is put into electric jacket, regulate the electric jacket temperature to higher 2～3 ℃ than the boiling point of pyridine, the speed controlling of distillate is about 60 of per minutes, after catcher cleans with an amount of distillate, collect distillate, liquid in the flask to be distilled stops heating when also remaining 20～30ml left and right sides, puts to room temperature, and distillate is poured into cleaning, in the anhydrous Brown Glass Brown glass bottles and jars only, add behind an amount of potassium hydroxide airtightly, shading is preserved standby.Chemosynthesis: get dithranol raw material 10g and heavily steam benzene 400ml and place the three neck reaction bulbs of putting into ice-water bath, stir, dithranol is dissolved in the benzene as far as possible, when the question response liquid temp is reduced to 7 ℃ ± 1 ℃, adds and heavily steam anhydrous pyridine 40ml, behind the stir about 2 minutes, slowly add chloroacetic chloride 40ml, stirring reaction adds the about 250ml washing of distilled water after 30 minutes, mixed liquor is put in the separatory funnel, leave standstill a moment, isolate upper strata liquid, add anhydrous sodium sulfate 40g, shake well, the back is after the lucifuge place places dry 1.5 hours, put into rotary evaporator, addend grain zeolite, water-bath is concentrated into about 20ml, placement is spent the night and is caused the product crystallization and separate out fully, the recrystallization of synthetic product: the concentrated solution that placement is spent the night is transferred in the buchner funnel, and decompress filter gets yellowish red color acicular crystal, put under the infrared lamp oven dry, weigh 7.71g.The crystallization of gained is added an amount of glacial acetic acid, after it is dissolved in 90 ℃ hot bath just, add 2～3ml glacial acetic acid more in addition, filtered while hot, filtrate are put to room temperature, the about 2hr in back that separates out fully to be crystallized, put decompress filter in the buchner funnel, put under the infrared lamp after the drying, glassy yellow acicular crystal, i.e. 10-acetyl dithranol.Get carbomer-94010g and add 700ml purified water placement 24hr, abundant swelling, after the 10-acetyl dithranol of recipe quantity and the salicylic acid fine powder 20g that crosses 80 mesh sieves added 150g glycerol and grind well, add in good carbomer-940 substrate of swelling, stir, again with after the dissolving in ethyl hydroxybenzoate 1g, ascorbic acid 0.5g and the essence 1ml adding 5ml ethanol, add in the substrate that contains principal agent and stir, add triethanolamine 10ml at last and regulate pH value between 6～7, remaining purified water is added to full dose, stir evenly packing, promptly.
Claims (3)
1,10-acetyl dithranol hydrogel adhesive, it is characterized in that: the raw material of making the weight ratio of gel comprises: 10-acetyl dithranol 3g-23.7g, salicylic acid 17g-23g, glycerol 120g-160g, carbomer-9408g-12g, ethyl hydroxybenzoate 0.5g-1.5g, triethanolamine 7ml-12ml, ascorbic acid 0.5g-1.5g, ethanol 3ml-7ml, essence 0.5ml-1.5ml, purified water 700ml-850ml.
2,10-acetyl dithranol hydrogel adhesive according to claim 1, it is characterized in that: the raw material of making the weight ratio of gel comprises: 10-acetyl dithranol 11g, salicylic acid 20g, glycerol 150g, carbomer-94010g, ethyl hydroxybenzoate 1g, triethanolamine 10ml, ascorbic acid 0.5g, ethanol 5ml, essence 1ml, purified water 800ml.
3, the preparation method of 10-acetyl dithranol hydrogel adhesive according to claim 1 and 2, it is characterized in that: get the dithranol raw material and heavily steam benzene and place the three neck reaction bulbs of putting into ice-water bath, stir, make dithranol be dissolved in the benzene as far as possible, when the question response liquid temp is reduced to 7 ℃ ± 1 ℃, add and heavily steam anhydrous pyridine, behind the stir about 2 minutes, slowly add chloroacetic chloride, stirring reaction adds distilled water and washs approximately after 30 minutes, mixed liquor is put in the separatory funnel, leave standstill a moment, isolate upper strata liquid, add anhydrous sodium sulfate, shake well, the back is after the lucifuge place places dry 1.5 hours, put into rotary evaporator, addend grain zeolite, water-bath is concentrated into approximately, placement is spent the night and is caused the product crystallization and separate out fully, get carbomer-94010g and add the 700ml purified water and place 24hr, abundant swelling is after the 10-acetyl dithranol and the salicylic acid fine powder 20g that crosses 80 mesh sieves of recipe quantity added 150g glycerol and grind well, add in good carbomer-940 substrate of swelling, stir, again with ethyl hydroxybenzoate 1g, ascorbic acid 0.5g and essence 1ml add in the 5ml ethanol after the dissolving, add in the substrate that contains principal agent to stir, add triethanolamine 10ml at last and regulate pH value between 6～7, remaining purified water is added to full dose, stir evenly, packing, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CNA2008101403470A CN101380293A (en) | 2008-10-10 | 2008-10-10 | 10-acetyl-dithranol hydrogel and preparation method thereof |
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| CNA2008101403470A CN101380293A (en) | 2008-10-10 | 2008-10-10 | 10-acetyl-dithranol hydrogel and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102139111A (en) * | 2010-12-29 | 2011-08-03 | 济南市皮肤病防治院 | Water-soluble matrix and application thereof in preparation of dithranol water-soluble preparations |
| CN103006537A (en) * | 2011-12-11 | 2013-04-03 | 西安泰科迈医药科技有限公司 | Gel preparation for treating psoriasis and preparation method thereof |
-
2008
- 2008-10-10 CN CNA2008101403470A patent/CN101380293A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102139111A (en) * | 2010-12-29 | 2011-08-03 | 济南市皮肤病防治院 | Water-soluble matrix and application thereof in preparation of dithranol water-soluble preparations |
| CN103006537A (en) * | 2011-12-11 | 2013-04-03 | 西安泰科迈医药科技有限公司 | Gel preparation for treating psoriasis and preparation method thereof |
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Open date: 20090311 |