CN101468006B - Compound pharmaceutical composition containing doxepin and nicotinic amide - Google Patents
Compound pharmaceutical composition containing doxepin and nicotinic amide Download PDFInfo
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- CN101468006B CN101468006B CN2007103040922A CN200710304092A CN101468006B CN 101468006 B CN101468006 B CN 101468006B CN 2007103040922 A CN2007103040922 A CN 2007103040922A CN 200710304092 A CN200710304092 A CN 200710304092A CN 101468006 B CN101468006 B CN 101468006B
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Abstract
A compound medicament composition has doxepin and nicotinamide. 1g of medicament composition contains 5-100mg of doxepin and 1-100mg of nicotinamide. The inventive medicament composition is applied to the treatment of neurodermatitis or atopic dermatitis which has good effectiveness and uneasy recurrence.
Description
Technical field:
The present invention relates to a kind of compound medicament composition that contains doxepin and nicotiamide, and doxepin and the application of nicotiamide compound recipe aspect preparation treatment neurodermatitis and atopic dermatitis medicine.
Background technology:
Neurodermatitis and atopic dermatitis are two kinds of chronic skin diseases that refractory is healed, and existing medicine mostly curative effect is not satisfactory, and easily recurrence, and side effects of pharmaceutical drugs etc. brings many miseries to patient.
Neurodermatitis has another name called chronic simple lichen, is a kind of chronic, common skin delayed ischemic neurological deficits dermatoses, is feature with violent pruritus and skin lichen sample pathological changes.Atopic dermatitis (Atopic Dermatitis, AD) claim again atoipc dermatitis, send the biography allergic dermatitis, be a kind of chronic, recurrent, pruritus, inflammatory skin disease, usually occur in the patient of anaphylactic disease personal history or family history.
Doxepin has another name called doxepin, is a kind of tricyclic antidepressant, clinically uses its hydrochlorate more, and tradition is used for the treatment of the depressive psychosis patient.Be developed as emulsifiable paste by U.S. Gen Derm company in 1998, and be used for the treatment of dermatosiss such as eczema.
There is the bibliographical information doxepin can treat neurodermatitis.As report treatment 30 routine neurodermatitis patients such as Wang Lei, 4 examples of fully recovering (cure rate 13.3%), produce effects 15 examples (obvious effective rate 50%) (2004 the 13rd the 10th phases of volume of Chinese Journal of New Drugs).Zhu Min has just waited report doxepin treatment neurodermatitis patient 50 examples, 23 examples of fully recovering (cure rate 46%), produce effects 13 examples (obvious effective rate 26%) (Chinese leprosy dermatosis magazine the 19th the 3rd phase of volume of December in 2003).Chen Xiaoxu, Chen Guoyu report doxepin is treated 35 routine neurodermatitis patients, 9 examples of fully recovering (cure rate 26%), produce effects 11 examples (obvious effective rate 31%) (2005 the 2nd the 2nd phases of volume of contemporary Chinese skin science magazine).More than Bao Dao clinical effectiveness difference is bigger.Cure rate is 13.3%～46%.
Not ideal enough with doxepin treatment atopic dermatitis and neurodermatitis curative effect, and easily recurrence.
Nicotiamide (Nicotinamide, niacinamide) has another name called vitamin B3, vitamin PP. and niacin amide, chemistry 3-ascorbyl palmitate by name is used for prevention and dermatosiss such as treatment pellagra, acne at present clinically.
Do not see the report of relevant nicotiamide treatment neurodermatitis and atopic dermatitis as yet.The elaboration of the auxiliary treatment or the molecule mechanism aspect of a small amount of atopic dermatitis is only arranged.Studied the skin moistening effect of 2% nicotiamide ointment as Soma etc. to atopic dermatitis patients.Think that nicotiamide is a kind of than the more effective wetting agent of white vaseline, can be used as auxiliary treatment (the Soma Y of atopic dermatitis, Kashima M, Imaizumi A, et al.Moisturizing effects of topical nicotinamide onatopic dry skin.Int J Dermatol, 2005,44:197-202).Mohammad Reza Namazi has summarized nicotiamide to the effect that the spy answers dermatitis from the molecule mechanism aspect, as a kind of PARP-1 inhibitor, can reduce the expression of inflammatory mediator absorbing molecules; Can increase the synthetic of ceramide, thereby improve the barrier function of skin; Can suppress NO synthetic grade (Mohammad Reza Namazi.Nicotinamide as a potential addition to the anti-atopic dermatitisarmamentarium.International Immunopharmacology 2004,4:709-712).
To sum up, not only do not see the report of relevant nicotiamide treatment neurodermatitis and atopic dermatitis as yet.Do not have two kinds of medication combined medications of doxepin and nicotiamide yet, or form the report of compound treatment other diseases.
Summary of the invention:
The purpose of this invention is to provide a kind of compound medicine for the treatment of neurodermatitis and atopic dermatitis, and the curative effect height, easy to use, be difficult for recurrence.
The invention provides a kind of compound medicament composition that contains doxepin and nicotiamide, can realize the foregoing invention purpose.
Described doxepin and the nicotiamide content in compositions is the treatment effective dose, and is cooperative effective quantity.Concrete content range is: in the 1g pharmaceutical composition, contain doxepin 5～100mg, nicotiamide 1～100mg; Preferred content is: the 1g pharmaceutical composition contains doxepin 20～60mg, nicotiamide 5～50mg.
Described doxepin comprises its cis-trans-isomer form and the acceptable salt of medicine thereof.The acceptable salt of described medicine comprises hydrochlorate, maleate, preferred salt hydrochlorate.
Described nicotiamide comprises its preceding donor nicotinic acid (nicotinic acid can be converted into nicotiamide in vivo).The acceptable salt of medicine that also comprises nicotiamide, its preceding donor and nicotinic acid is as the nicotiamide Ascorbate.Because nicotinic acid can distend the blood vessels, and the rubescent defective of the colour of skin of making is arranged, so preferred nicotiamide.
The barrier function damage of neurodermatitis, atopic dermatitis and other drying property dermatosis patient skins, the percutaneous loss of moist increases, and cutaneous sensibility is high and comparatively dry, is the key factor of this class dermatosis morbidity.It is mainly relevant with the minimizing of nicotinamide material in the horny layer to form reason.
Doxepin reduces the release of inflammatory factors such as histamine by suppressing nervous system, reduce to discharge neuropeptide, thereby plays the effect of alleviating neuropathic dermatitis symptom.After doxepin share nicotiamide, can increase the synthetic of ceramide, improve the barrier function of skin, can reduce the sensitivity of skin.In addition, nicotiamide is a kind of antioxidant, has good antiphlogistic effects.It can effectively prevent the damage that cell and cell membrane are avoided free radical, the ultra-oxygen anion free radical that works in diminishing inflammation, can suppress phosphodiesterase and suppress mast cell degranulation, can also directly suppress the release of histamine receptor and histamine, and suppress the neutrophilic granulocyte chemotactic, suppress the regulating action of lymphocytic conversion and gene.The mechanism of its antiinflammatory action is different from doxepin, behind two drug combinations, from different approach inflammation-inhibiting media, so for neurodermatitis, inflammatory skin diseases such as atopic dermatitis have synergism, can make two medicines better bring into play curative effect.
In order to reach better therapeutic, can also add Percutaneous absorption enhancer in the said composition, can make medicine by horny layer and be easy to absorb.Percutaneous absorption enhancer is selected from azone and analog thereof, dimethyl sulfoxine, decyl methyl sulfoxide, oleic acid, preferred azone.The content of Percutaneous absorption enhancer is according to the design of conventional medicine prescription.
Can also add the cutin softening composition in the said composition, this class material energy horny layer softening keeps the moisture in the skin, thereby makes the easier skin that passes through of medicine.The cutin softening composition is selected from carbamide, carbamide capsule, hyaluronic acid sodium.The content of cutin softening composition is according to the design of conventional medicine prescription, and content commonly used is 4～6%.
Needs according to concrete dosage form, can in said composition, add antioxidant, as sodium sulfite, vitamin C, vitamin E, butylated hydroxyarisol (BHA), 2,6-d-tert-butyl-p-cresol (BHT), preferred anti-oxidants are butylated hydroxyarisol (BHA), vitamin E.The content of antioxidant is according to the design of conventional medicine prescription.
This compositions can be made the multiple external preparation form that is suitable for treating neurodermatitis and atopic dermatitis, as ointment, ointment, gel etc., and according to the conventional preparation method preparation of various dosage forms.
Experimental results show that through the clinical comparison with doxepin and two kinds of medicine lists of nicotiamide medicine: compound medicament composition of the present invention has the following advantages when treatment neurodermatitis and atopic dermatitis:
1. better efficacy is better than the single respectively usefulness of two kinds of medicines.
2. relapse rate is low.Clinical verification, this combination treatment neurodermatitis and atopic dermatitis recurrence are still less.
The present invention has carried out following experiment:
By to 2,4-dinitrochlorobenzene (DNCB) inductive Cavia porcellus chronic eczema model and 4-aminopyridine (4-AP) cause the effect that mice pruritus model comes the compound cream of comparison doxepin hydrochloride emulsifiable paste, nicotiamide emulsifiable paste and two components, estimate the therapeutical effect of compound cream to Cavia porcellus chronic eczema and mice pruritus.
Experimental result proves:
1. separately external doxepin hydrochloride emulsifiable paste or nicotiamide emulsifiable paste all can suppress the ear swelling of chronic eczema Cavia porcellus due to the DNCB, but it is more remarkable that compound cream suppresses the ear swelling effect, the pathological change that alleviates chronic eczema is more obvious, can act on similarly to fourth, and therapeutical effect obviously is better than folk prescription.
2. compare with model group, the doxepin hydrochloride emulsifiable paste can suppress the mice pruritus, and the nicotiamide emulsifiable paste does not have obvious inhibitory action to the mice pruritus, and it is more remarkable that compound cream suppresses the reaction of mice pruritus, can be similar to fourth, and itching-relieving action obviously is better than folk prescription.
The specific embodiment:
The following examples are for illustrating prescription of the present invention, but do not limit the scope of the invention.
Embodiment 1 doxepin hydrochloride and nicotiamide emulsifiable paste ()
Doxepin hydrochloride 50g, nicotiamide 50g, hard ester acid 150g, glyceryl monostearate 45g white vaseline 12g, liquid paraffin 15g, hexadecanol 20g, sorbester p18 5g, azone 5g polysorbate60 40g, glycerol 50g ethyl hydroxybenzoate 1g, distilled water (regulating PH with hydrochloric acid is 5.5-7.5) adds to 1000g
Preparation method: with an amount of dissolved in distilled water doxepin hydrochloride.Get white vaseline, ethyl hydroxybenzoate, hexadecanol, hard ester acid, glyceryl monostearate, liquid paraffin, span melts in water-bath, be heated to 80 ℃ oil phase; Other gets nicotiamide, azone, tween, glycerol, adding distil water, heating in water bath to 80 ℃ water.Water slowly is added in the oil phase, and the limit edged stirs, until condensation.In condensation process, add above-mentioned doxepin hydrochloride solution, promptly get the emulsifiable paste that contains nicotiamide and doxepin hydrochloride.
Embodiment 2 doxepin hydrochlorides and nicotiamide emulsifiable paste (two)
Doxepin hydrochloride 100g, nicotiamide 1g, octadecanol 150g, vaseline 150g, Tween 80 30g, glycerol 60g, carbamide 45g, ethyl hydroxybenzoate 1g, distilled water (regulating PH with hydrochloric acid is 5.5-7.5) adds to 1000g
Preparation method: with an amount of dissolved in distilled water doxepin hydrochloride, get vaseline, ethyl hydroxybenzoate, octadecanol and in water-bath, melt, be heated to 75 ℃ oil phase; Other gets nicotiamide, Tween 80, glycerol, carbamide, adding distil water, heating in water bath to 80 ℃ water.Water slowly is added in the oil phase, and the limit edged stirs, until condensation.In condensation process, add doxepin hydrochloride solution, promptly get the emulsifiable paste that contains doxepin hydrochloride and nicotiamide.
Embodiment 3 doxepin hydrochlorides and nicotiamide emulsifiable paste (three)
Doxepin hydrochloride 5g, nicotiamide 100g, stearic acid 12.5g, glyceryl monostearate 17g, Cera Flava 5g, ceresine 70g, liquid Paraffin 420ml, white vaseline 70g, double stearic acid aluminium 10g, calcium hydroxide 1g, ethyl hydroxybenzoate 1g, carbamide 50g, distilled water (regulating PH with hydrochloric acid is 5.5-7.5) adds to 1000g
Preparation method: with an amount of dissolved in distilled water doxepin hydrochloride and nicotiamide.Get stearic acid, glyceryl monostearate, Cera Flava, ceresine heat fused in water-bath, add liquid Paraffin, white vaseline, double stearic acid aluminium again, be heated to 85 ℃.In addition calcium hydroxide, ethyl hydroxybenzoate, carbamide are dissolved in the distilled water, are heated to 85 ℃, add gradually in the oil phase, the limit edged stirs.Under agitation add doxepin hydrochloride and nicotinamide soln, condensation promptly gets emulsifiable paste.
Embodiment 4 doxepin hydrochlorides and nicotiamide Ascorbate emulsifiable paste
Nicotiamide Ascorbate 5g, doxepin hydrochloride 60g, glyceryl monostearate 70g, stearic acid 120g, white vaseline 80g, sodium lauryl sulphate 8g, glycerol 85g, ethyl hydroxybenzoate 1g, allantoin 50g, distilled water (regulating PH with hydrochloric acid is 5.5-7.5) adds to 1000g
Preparation method: with an amount of dissolved in distilled water doxepin hydrochloride and nicotiamide Ascorbate, getting white vaseline, glyceryl monostearate, stearic acid melts in water-bath, be heated to 80 ℃, slowly add other adjuvant compositions that are dissolved in the water in advance and are heated to 80 ℃, until condensation.In condensation process, add nicotiamide Ascorbate and doxepin hydrochloride solution, promptly get the emulsifiable paste that contains nicotiamide Ascorbate and doxepin hydrochloride.
Embodiment 5 maleic acid doxepins and nicotinic acid gel
Nicotinic acid 50g, maleic acid doxepin 20g, Acritamer 940 9g, ethanol 60g, glycerol 50g, Tween 80 2.5g, ethyl hydroxybenzoate 1.5g, sodium hydroxide 3.6g, distilled water (regulating PH with hydrochloric acid is 5.5-7.5) adds to 1000g
Method for making: dissolved in distilled water nicotinic acid and maleic acid doxepin take a morsel, carbomer is mixed with Tween 80 and 250ml distilled water, after sodium hydroxide is dissolved in excess water, liquid stirs evenly in the adding, principal agent solution adds upward, and liquid stirs well, ethyl hydroxybenzoate is dissolved in adding behind an amount of ethanol stirs evenly, promptly get the gel that contains nicotinic acid and maleic acid doxepin.
Embodiment 6 doxepin hydrochlorides and nicotiamide ointment
Nicotiamide 70g, doxepin hydrochloride 50g, lanoline 60g, paraffin 40g, octadecanol 50g, Yellow Vaselin 798g
Preparation method: the distilled water that takes a morsel, accent PH is 5.5-7.5, and dissolving nicotiamide and doxepin hydrochloride add in the 30g paraffin, and mix homogeneously makes paraffin fully absorb moisture.It gets his adjuvant composition heating in water bath fusing, stirs, and adds the paraffin that is dissolved with principal agent, stirs, cools off, and promptly gets the ointment that contains nicotiamide and doxepin hydrochloride.
The therapeutical effect of chronic dermatitis Cavia porcellus due to 1 couple of DNCB of experimental example
1. test objective: adopt the DNCB sensitized guinea pig, excite repeatedly to cause that the pathological change of chronic eczema appears in local skin, this animal model is commonly used to estimate the curative effect of treatment chronic eczema medicine.This test is intended to the effect to the chronic eczema Cavia porcellus of comparison Doxepin Hydrochloride Cream in Animals, nicotiamide emulsifiable paste and two component compound creams, estimates the therapeutical effect of compound cream to chronic eczema.
2. trial drug:
Doxepin hydrochloride emulsifiable paste (containing 5% doxepin hydrochloride)
Nicotiamide emulsifiable paste (containing 5% nicotiamide)
The pharmaceutical composition of embodiment 1 (containing 5% doxepin hydrochloride and 5% nicotiamide)
Hydrocortisone butyrate ointment (containing 0.1% hydrocortisone butyrate)
Blank emulsifiable paste (embodiment 1 removes doxepin hydrochloride and the blank substrate of nicotiamide)
3. experimental technique
Get 50 of 250-350g Cavia porcelluss, be divided into 5 groups at random, 10 every group, be respectively model group, doxepin hydrochloride emulsifiable paste group, nicotiamide emulsifiable paste group, compound cream group, hydrocortisone butyrate group (can organize) hereinafter to be referred as fourth.Every back of the body cervical region is shaved a mao 2cm * 2cm size, is coated with this place's sensitization outward with 5%DNCB acetone soln 100ul, and be coated with the 0.1%DNCB acetone soln outside 2 all backs and excite in the auris dextra inboard, 1 time/week, continuous 4 times.Last excites back beginning in the 4th day, respectively organizes respectively at the inboard evenly outer corresponding medicine that is coated with of auris dextra, and 0.2ml//time, 2 times/d, successive administration 7d, model group is coated with blank emulsifiable paste outward.Put to death all animals next day, cut the Cavia porcellus ears, lay auricle in left and right sides ear middle part same position, weigh, calculate ear swelling degree and swelling rate by following formula with the card punch of diameter 9mm; And the tissue of laying fixed with 10% formalin, pathological observation is carried out in embedding then, section, HE dyeing.
Swelling degree (mg)=auris dextra sheet weight-left auricle is heavy
4. result of the test
A. to the influence of Cavia porcellus chronic eczema model ear swelling
Compare with model group, the doxepin hydrochloride emulsifiable paste, the emulsifiable paste of nicotiamide emulsifiable paste and two component compound recipes all can alleviate the Cavia porcellus ear swelling, reduces swelling rate (P＜0.05, P＜0.01).Compare with two folk prescriptions, it is more remarkable that compound cream suppresses the effect of ear swelling, obviously is better than folk prescription, has significant difference (P＜0.05, P＜0.01).Can organize comparison with fourth, the effect that two folk prescriptions suppress ear swelling obviously reduces, and has significant difference (P＜0.05, P＜0.01), compound cream then to fourth can inhibitory action similar, no significant difference.The results are shown in Table 1.
The influence of table 1 pair Cavia porcellus chronic eczema model ear swelling (n=10,
)
| Group | Swelling degree (mg) | Swelling rate (%) |
| Model group compound cream group doxepin hydrochloride emulsifiable paste group nicotiamide emulsifiable paste group fourth can be organized | 26.89±7.93 10.18±5.83 **+△△ 16.27±6.54 *# 19.50±7.16 *## 9.96±6.02 ** | 49.79±16.65 20.07±10.14 **+△△ 31.48±13.61 *# 35.06±12.42 *## 19.04±12.23 ** |
Annotate: and model group is relatively,
*: P＜0.05,
*: P＜0.01;
Compound cream group and doxepin hydrochloride group compare ,+: P＜0.05;
Compound cream group and nicotiamide group compare, △ △ P＜0.01;
Can organize comparison with fourth, #:P＜0.05, ##:P＜0.01.
B. to the influence of Cavia porcellus chronic eczema pathological change
Through pathological examination, each pathological change degree of organizing the Cavia porcellus auricle is: model group＞nicotiamide emulsifiable paste group＞doxepin hydrochloride emulsifiable paste group＞compound cream group＞fourth can be organized＞left ear normal control.
Concrete pathological change is as follows:
Left side ear normal control: the auricle tissue is normal, and the epithelial surface keratinization forms horny layer, does not see obvious edema and proliferation of fibrous tissue in the skin corium, the inflammatory cell that indivedual accidental minorities of specimen are dispersed in.
Model group: horny layer obviously thickens, and spine cell's number of plies increases; Intradermal is seen vasodilation, hyperemia, part animal tissue edema, a large amount of cell infiltration.
The compound cream group: keratinization of epidermis obviously alleviates, and spine cell's number of plies is less.As seen minority animal intradermal degree of taking a favourable turn tissue edema is dispersed in cell infiltration on a small quantity.
Doxepin hydrochloride emulsifiable paste group: the top layer keratinization is lighter, and spine cell's number of plies is less, alleviates than the model group pathological changes.Part animal dermal tissue has the congestion of blood vessel, tissue edema, and as seen a small amount of cell infiltration is arranged.
Nicotiamide emulsifiable paste group: the top layer keratinization is lighter, and spine cell's number of plies is still more.The expansion of dermal tissue visible vessels has cell infiltration.
Fourth can be organized: top layer keratinization degree is not obvious, and this recovery of prickle cell layer base is normal, occurs vasodilation individually, visible single cell infiltration.
5. conclusion
The result shows, separately external doxepin hydrochloride emulsifiable paste or nicotiamide emulsifiable paste all can suppress the ear swelling of chronic eczema Cavia porcellus due to the DNCB, but it is more remarkable that compound cream suppresses the ear swelling effect, the pathological change that alleviates chronic eczema is more obvious, can act on similarly to fourth, therapeutical effect obviously is better than folk prescription.
2 couples of 4-AP of experimental example cause the influence of mice pruritus
1. test objective: pruritus is one of atopic dermatitis and the common clinical symptoms of neurodermatitis.There are some researches show that pruritus is relevant with histamine release.4-AP brings out mice and licks precursor reactant also with to promote that mastocyte discharges histamine relevant, and this model is commonly used to estimate the itching-relieving action of medicine.This research purpose is intended to the inhibitory action of the compound cream of comparison Doxepin Hydrochloride Cream in Animals, nicotiamide emulsifiable paste and two components to the mice pruritus, estimates the itching-relieving action of compound cream.
2. trial drug: with experimental example 1
3. test method
Get 50 of 18-22g Kunming mouses, male and female half and half are divided into 5 groups at random, and 10 every group, being respectively model group, doxepin hydrochloride emulsifiable paste group, nicotiamide emulsifiable paste group, compound cream group, fourth can organize.Mouse tail back depilation 1 * 1cm2, and give that depilation place is evenly outer only to be coated with corresponding medicine 0.2ml/, 1 time/d, 7d continuously, model group is coated with blank emulsifiable paste outward.1h after the last administration is at administration center subcutaneous injection 4-AP 1mg/kg.Lick the body number of times in the opening entry 10min immediately after the administration.
4. result of the test
Compare with model group, the Doxepin Hydrochloride Cream in Animals group can suppress mice pruritus reaction (P＜0.05), and the nicotiamide emulsifiable paste does not have obvious inhibitory action to the mice pruritus.Compound cream suppresses mice pruritus effect more significantly (P＜0.01), compares with two folk prescriptions, obviously is better than folk prescription, has significant difference (P＜0.01).Can organize comparison with fourth, two folk prescription itching-relieving actions obviously descend, and have significant difference (P＜0.05, P＜0.01), and the compound cream itching-relieving action can be similar to fourth, no significant difference.The results are shown in Table 2.
Table 2 pair 4-AP induced mice lick precursor reactant influence (n=10,
)
| Group | Lick the body number of times in the 10min |
| Model group compound cream group doxepin hydrochloride emulsifiable paste group nicotiamide emulsifiable paste group fourth can be organized | 42.9±10.5 16.8±9.7 **++△△ 30.7±10.2 *# 37.2±11.8 ## 17.5±10.6 ** |
Annotate: and model group is relatively,
*: P＜0.05,
*: P＜0.01;
Compound cream group and doxepin hydrochloride group compare, ++: P＜0.01;
Compound cream group and nicotiamide group compare, △ △ P＜0.01;
Can organize comparison with fourth, #:P＜0.05, ##:P＜0.01.
5. conclusion
The result shows, compares with model group, and the doxepin hydrochloride emulsifiable paste can suppress the mice pruritus, and the nicotiamide emulsifiable paste does not have obvious inhibitory action to the mice pruritus.It is more remarkable that compound cream suppresses the reaction of mice pruritus, can be similar to fourth, and itching-relieving action obviously is better than folk prescription.
Confirm that by above test doxepin hydrochloride and the external of nicotiamide composition compound preparation can obviously suppress the Cavia porcellus ear swelling, significantly improve ear's pathological change, obviously suppress the mice pruritus, therapeutical effect obviously is better than two single preparationss of ephedrine.We think doxepin hydrochloride and nicotiamide form compound preparation improve aspect chronic eczema and the inhibition skin pruritus more obvious than two folk prescription effects.
Claims (8)
1. an externally used compound pharmaceutical composition for the treatment of neurodermatitis or atopic dermatitis contains doxepin 5～100mg, nicotiamide or nicotinic acid 1～100mg in the 1g pharmaceutical composition; Described doxepin comprises its cis-trans-isomer form and the acceptable salt of medicine thereof; Described nicotiamide or nicotinic acid comprise the acceptable salt of the medicine of nicotiamide or nicotinic acid.
2. the described compound medicament composition of claim 1 contains doxepin 20～60mg in the 1g pharmaceutical composition, nicotiamide 5～50mg.
3. claim 1 or 2 described compound medicament compositions, the acceptable salt of described doxepin medicine is hydrochlorate or maleate.
4. claim 1 or 2 described compound medicament compositions contain and are selected from azone, dimethyl sulfoxine, decyl methyl sulfoxide or oleic Percutaneous absorption enhancer.
5. claim 1 or 2 described compound medicament compositions contain the keratolytic that is selected from carbamide, carbamide capsule or hyaluronic acid sodium.
6. claim 1 or 2 described compound medicament compositions contain and are selected from sodium sulfite, vitamin C, vitamin E, butylated hydroxyarisol or 2, the antioxidant of 6-d-tert-butyl-p-cresol.
7. claim 1 or 2 described compound medicament compositions, its dosage form comprises ointment, ointment, gel.
8. treat the application of neurodermatitiss or atopic dermatitis medicine with claim 1 or 2 described compound medicament composition preparations.
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| FR3021870B1 (en) * | 2014-06-06 | 2017-10-27 | Espa Sa-Experts In Science & Product Achievements | DERMATOLOGICAL COMPOSITION BASED ON NIACINAMIDE |
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| Title |
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| 田剑贞等.特应性皮炎的治疗进展.《中国中西医结合皮肤性病学杂志》.2005,(第03期), * |
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