CN1306823A - Ointment for treating dermatosis and its preparation - Google Patents
Ointment for treating dermatosis and its preparation Download PDFInfo
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Abstract
A dermatosis treating ointment consists of active components and matrix in the ratio of 1-3 to 97-99; the active components consists of Ketoconazole or Itraconazole 50-70 wt%, Halcinonide 5-15 wt% and Neomycin 25-40 wt%; and the matrix consists of stearic acid 10-15 wt%, vaseline 5-15 wt%, tween-80 2-5 wt%, glycerol monostearate 5-10 wt%, fluid wax 2-5 wt% and distilled water the rest. The present invention also relates to the preparation process of the ointment.
Description
The present invention relates to dermopathic ointment formulation of a kind of treatment and preparation method thereof.
Dermatosis is a kind of commonly encountered diseases, frequently-occurring disease, and especially the geographic sickness rate of the moist high temperature in subtropical zone is higher.It is a lot of to cause dermopathic factor, and the various dermatosiss that cause because of fungus and/or antibacterial etc. are typically arranged.Pathomycete has funguses such as trichophyton, Candida albicans.Because the infection of above-mentioned fungus causes the people to suffer from tinea corporis, tinea cruris (mashed crotch) tinea manus and pedis; The tuft that bites and contact of mosquito causes dermatitis and allergic dermatitis etc., has a strong impact on people's routine work and life.Though the dermopathic medicine for external use kind of treatment is a lot of at present, but a kind of medicine has multiple-effect, quick-acting and efficiently treat dermopathic medicine for external use seldom simultaneously, great majority also belong to single current system and imitate preparation, as control dermatitis can not control tinea, that controls tinea can not control dermatitis, and for example at present commercially available tetracycline, erythromycin, compound neomycin ointment etc. are used for the treatment of the dermatosis that causes because of bacterial infection; Daktarin, PIKANGWANG and clotrimazole etc. then can only be used for the treatment of the dermatosis that causes because of fungal infection.Steroidal and hormone medicine then have only antiphlogistic effects as fluocinolone acetonide, omcilon, cortisone ointment etc., and fungus and bacterial infection are not had action effect.To the dermatosis of many mixed infections, then need multiple different medicine just can work.So not only increase the medication trouble, but also increased patient's financial burden.
The Chinese patent application 931091403 that the applicant of present patent application submitted on August 3rd, 1993 discloses a kind of treatment dermopathic " chloro-neocuprum ointment ", this ointment is main active component with ketoconazole, halcinonidedcorten and polygynax, and adds azone as coagent.This ointment can be used for the treatment of the multiple thereby dermatosis that cause former because of difference, but the cost height of said preparation, poor stability, and side effect is arranged.
An object of the present invention is at problems of the prior art, a kind of can treatment multiple thereby dermopathic pharmaceutical preparation of causing former because of difference is provided, thereby solve medication trouble in the treating for skin disease process of mixed infection, the problem that patient's financial burden is high.
The dermopathic pharmaceutical preparation that another object of the present invention provides that a kind of cost is low, preparation method simply can be treated multiple thereby initiation former because of difference.
The present inventor is through long term studies and experiment, by being screened with compatibility, tests a large amount of medicines, researched and developed out a kind of ointment formulation that can be used for the treatment of the various skin disease, said preparation is made up of active component and substrate, it is characterized in that described active component is by triumphant appropriate health azoles or the itraconazole of 50-70% (weight); The polygynax of the halcinonidedcorten of 5-15% (weight) and 25-40% (weight) is formed; Described substrate is by the stearic acid of 10-15% (weight); The vaseline of 5-15% (weight); The tween 80 of 2-5% (weight); The glyceryl monostearate of 5-10% (weight); The liquid paraffin of 2-5% (weight) and the distilled water of surplus are formed, and the weight ratio of described active component and described substrate is 1-3: 99-97.
According to ointment formulation of the present invention, wherein, described active component is preferably by triumphant appropriate health azoles or the itraconazole of 55-65% (weight); The polygynax of the halcinonidedcorten of 6-12% (weight) and 28-35% (weight) is formed; Described matrix optimization is by the stearic acid of 12-14% (weight); The vaseline of 8-12% (weight); The tween 80 of 3-4% (weight); The glyceryl monostearate of 7-8% (weight); The liquid paraffin of 3-4% (weight) and the distilled water of surplus are formed, and the weight ratio of described active component and described substrate is 1.5-2.5: 98.5-97.5.
According to ointment formulation of the present invention, wherein, described preparation is the oil-in-water type ointment formulation.
The present invention also provides the preparation method of aforesaid ointment formulation, may further comprise the steps:
(1) stearic acid, vaseline, glyceryl monostearate and liquid paraffin are joined in the container mixing and stirring under 70-75 ℃ temperature; Tween 80 and distilled water are joined in the container mixing and stirring under 70-75 ℃ temperature; Temperature is remained on 70-75 ℃, stir down, the mixed liquor of tween 80 and distilled water is joined in the mixed liquor of stearic acid, vaseline, glyceryl monostearate and liquid paraffin, stir, obtain substrate after the condensation;
(2) triumphant appropriate health azoles or itraconazole, halcinonidedcorten and polygynax are ground into fine powder respectively; Then, at first triumphant appropriate health azoles or itraconazole fine powder are joined in the mortar, add the substrate that an amount of above-mentioned steps (1) obtains again and grind well, and then add halcinonidedcorten successively, polygynax, add the substrate mixing by the dilution method that progressively increases and grind well, mix.
Several active constituents in the ointment formulation of the present invention have different pharmacological actions respectively, and the bacteriostatic test of each component shows: fluorine chlorine is relaxed and comfortable not to have bacteriostasis, but has powerful antiinflammatory action, and can strengthen antibiotic antibacterial effect; Polygynax is not obvious to the inhibitory action of fungus, but antibacterial is had tangible bacteriostatic activity; Triumphant appropriate health azoles or itraconazole have stronger inhibitory action to most of fungus, but to antibacterial unrestraint effect.The present inventor is through long-term a large amount of research and experiments, discovery is by carrying out combination and compatibility with these three kinds of drug components by aforesaid consumption, and the oil-in-water type ointment formulation that adopts aforesaid substrate to make, owing to have synergism between the active component, therefore can be used for the treatment of the various skin disease that causes because of different reasons, for example tinea cruris, tinea corporis, tinea manus and pedis, contact dermatitis, neurodermatitis, insect dermatitis, eczema, folliculitis, cutaneous Candida etc., therapeutic effect is good.
For ointment formulation of the present invention is to adopt water-in-oil type, still adopts oil-in-water type, and the present inventor has also carried out the contrast experiment.Experimental result is found: the fungistatic effect of oil-in-water type ointment formulation also will be got well various treating for skin disease effects than the good antimicrobial effect of water-in-oil type ointment formulation.Simultaneously, the oil-in-water type ointment formulation is little to the dustiness of medicated clothing.Therefore, ointment formulation of the present invention adopts oil-in-water type.
In the ointment formulation of the present invention, described active component such as triumphant appropriate health azoles or itraconazole, polygynax and halcinonidedcorten are the commercially available prod.
Some physical parameters of ointment formulation of the present invention are as follows:
Fluorine content: 3.4-4.4%
Chlorinity: 〉=7.0%
Other steroidals :≤2%
Loss on drying :≤1.0%
Residue on ignition :≤0.1%
Below in conjunction with embodiment and test example the present invention is further illustrated.But it should be understood that the present invention is not restricted to these embodiment and test example.
Embodiment
Embodiment 1
150 gram stearic acid, 110 gram vaseline, 85 gram glyceryl monostearates and 45 gram liquid paraffin are joined in the container mixing and stirring under 75 ℃ temperature; 30 gram tween 80s and 580 gram distilled water are joined in another container mixing and stirring under 75 ℃ temperature.Temperature is remained on 75 ℃, stir down, the mixed liquor of tween 80 and distilled water is joined in the mixed liquor of stearic acid, vaseline, glyceryl monostearate and liquid paraffin, stir, obtain substrate after the condensation.
Triumphant appropriate health azoles (Belgian Yang Sen pharmaceutical factory produce), halcinonidedcorten (production of Tianjin Pharma Inc.) and polygynax (Shanghai No. 3 Pharmaceutical Factory's production) are ground into fine powder respectively, sieve with No. 6 sieves, extracting screen underflow obtains the triumphant appropriate health azoles of 15 grams, 1.5 gram halcinonidedcorten and 5,000,000 u polygynax fine powders.Then, at first triumphant appropriate health azoles fine powder is joined in the mortar, add 50 substrate that obtain of gram above-mentioned steps (1) again and grind well, and then add halcinonidedcorten, polygynax successively, add the substrate mixing by the dilution method that progressively increases and grind well, mix, obtain ointment of the present invention.
Embodiment 2-4
Step and method according to identical with embodiment 1 prepare the dermopathic ointment formulation of treatment of the present invention, just the consumption difference of each component.(unit is gram in the table) as shown in the table.
Comparative Examples
| Embodiment | Triumphant appropriate health azoles | Itraconazole | Halcinonidedcorten | Polygynax | Stearic acid | Vaseline | Glyceryl monostearate | Liquid paraffin | Tween-80 | Distilled water |
| ???2 | ?- | ???15 | ????1.5 | 6,000,000 u | ????150 | ???100 | ???80 | ??70 | ???20 | Add to 1000 |
| ???3 | ?10 | ????- | ????1.0 | 5,000,000 u | ????180 | ????80 | ????70 | ??80 | ???25 | Add to 1000 |
| ???4 | ?- | ????8 | ????0.8 | 4,000,000 u | ????130 | ???120 | ????85 | ??75 | ???30 | Add to 1000 |
Triumphant appropriate health azoles (Belgian Yang Sen pharmaceutical factory produce), halcinonidedcorten (production of Tianjin Pharma Inc.) and polygynax (Shanghai No. 3 Pharmaceutical Factory's production) are ground into fine powder respectively, sieve with No. 6 sieves, extracting screen underflow obtains the triumphant appropriate health azoles of 15 grams, 1.5 gram halcinonidedcorten and 5,000,000 u polygynax fine powders.Then, at first triumphant appropriate health azoles fine powder is joined in the mortar, adding 50 gram vaseline again grinds well, and then add halcinonidedcorten, polygynax successively, add the vaseline ad pond om by the dilution method that progressively increases and reach 1000 grams, mix, obtaining with triumphant appropriate health azoles, halcinonidedcorten and polygynax is that active component, vaseline are the ointment of substrate.
Ointment formulation of the present invention has good bacteriostatic activity.Following table is several different medicines to the synopsis of the bacteriostatic activity of the ointment formulation of the bacteriostatic activity of various antibacterial or fungus and the embodiment of the invention 1.Bacteriostatic activity is to suppress diameter (millimeter) expression in the table.
| The medicine strain | Halcinonidedcorten | Polygynax | Triumphant appropriate health azoles | Nystatin | The Comparative Examples ointment | The present invention |
| Trichophyton | ??- | ?????- | ?????20 | ????15.5 | ????23.5 | ???31.0 |
| The Rhodothece glutinis bacterium | ??- | ????7.7?5 | ????23.5 | ????18.0 | ????20.5 | ???30.0 |
| Ulotrichy sporidiole tinea bacterium | ??- | ?????- | ????21.75 | ????18.5 | ????21.0 | ???29.0 |
| Gypsum Fibrosum sheep trichophyton | ??- | ?????- | ????21.25 | ????17.2 | ????21.25 | ???36.0 |
| The rust trichophyton | ??- | ?????- | ????21.5 | ????16.5 | ????20.5 | ???31.5 |
| Saprophytic cryptococcus | ??- | ?????18 | ????17.5 | ????17.5 | ????18.5 | ???29.5 |
| Candida albicans 1 | ??- | ??????7 | ?????- | ????16.0 | ?????26 | ???26.7 |
| Candida albicans 2 | ??- | ??????- | ?????- | ????15.8 | ?????21 | ????24.0 |
| Golden yellow staphylococcus | ??- | ?????19.5 | ?????- | ?????- | ?????20.1 | ????24.5 |
As can be seen from the above table, ointment formulation of the present invention all has the activity of inhibition to dissimilar funguses and antibacterial, and suppresses active high.Test example test example 1 animal experiment 1, toxicity test:
(1) drug dose test
Animal subject: 10 heros of rat are female half and half, and are anosis pregnant, body weight 200g*10g.
10 heros of rabbit are female half and half, and are anosis pregnant, average weight 1.5kg.
Route of administration and dosage: gastric infusion, dosage is counted with per kilogram of body weight: 50 milligrams of triumphant appropriate health azoles or itraconazoles, 5 milligrams of halcinonidedcortens, polygynax 250,000 u.
Result of the test: administration 24 hours, observed the behaviors of two kinds of animals in 48 hours: the rhythm of the heart, breathing, defecation be no abnormal, do not have vomiting or faint from fear and take place, and none death was observed in administration in 72 hours.
Conclusion: by above-mentioned test, the suitable people's external of dosage dose more than 200 times the time, animal subject is remained safe.Therefore, ointment formulation of the present invention is safe and reliable as external used medicine to the people.
(2) long-term toxicity test for animals
Animal subject: 3 of rabbit, it is pregnant that body weight 1.5-2.0kg is anosis.
Dosage: count: triumphant appropriate health azoles or itraconazole 5mg, halcinonidedcorten 0.04mg, polygynax 2.5mg/Kg body weight/day by active component.
Route of administration: gastric infusion.
Test period: 30 days.
Test method: said medicine is added suitable quantity of water, and wiring solution-forming is irritated stomach every day once.
The result: body weight does not have obvious increase and decrease, hair such as preceding, feces no change, movable as usual, do not have any ANOMALOUS VARIATIONS.
Treating excess syndrome is tested one of rabbit, does not do execution of experimental rabbit contrast that performs an autopsy on sb, and does the pathological examination of important organ, observes organs such as the heart, lung, kidney, genitourinary system, experimental rabbit and normal rabbit contrast, Non Apparent Abnormality variation.
2, local application's toxicity, irritation test:
Select for use 12 of white rabbit to be respectively four groups, be divided into three and be subjected to an examination group and a blank group.The rabbit body weight is all at 1.5-2.0kg, and is anosis, pregnant.Choose area in rabbit trunk both sides and be 4 * 4cm 2, unhairing, by 1,2,3 group respectively at the ointment formulation of unhairing district coating embodiments of the invention 1.Each three rabbit that are subjected to the examination group respectively by 0.5,1.0, the ointment formulation of 1.5g/ amount coating embodiments of the invention 1 only.The substrate of the 4th group of coating embodiment of the invention 1 is made blank, every rabbit also by 0.5,1.0, the amount coating of 1.5g, cover wrapping with polyethylene film behind the coating and observe.With residual medicine in the careful flush away coating of warm water position and substrate and conscientiously observe the variation at coating position, after 12,24 hours, make observed and recorded afterwards after 4 hours.
The result: observe after 4 hours, 12 hours and 24 hours behind the coating, 3 all no abnormal changes of 12 rabbit that are subjected to examination group and blank group, local do not have congested, an edema, erythema, petechia more do not occur, make an exception and variation such as ulcer.Above-mentioned test is carried out 10 times continuously, has no significant change.
Conclusion: ointment formulation of the present invention is to the skin nonirritant, three dosage groups and blank, and local skin does not have difference basically, phenomenons such as hyperemia, redness, ecchymosis occur.Fur, diet, activity, the spiritual no abnormal variation of observation experiment rabbit also do not have the performance of any allergy symptoms simultaneously.Therefore, ointment formulation of the present invention is no local excitation and whole toxic reaction in the constant topical application, is the external used medicine of comparison safety.3, skin absorption test
Select five of anosis pregnant rat, the back is shaved off the big small size of 3 * 5cm, treat that its skin recovers normal, every ointment formulation 1g that is coated with the embodiment of the invention 1 covers immobilization with adhesive tape with plastic film.Respectively after 1,2,3,4,5 hour, the coating of rat is cleaned up, and, place with heparin and handled in vitro in time with cardiocentesis blood sampling 0.5ml, extraction serum is measured drug component concentration in the rat blood respectively with the HPLC method.
Result: do not measure triumphant appropriate health azoles (or itraconazole) and halcinonidedcorten in the blood in coating 1-2 hour, the triumphant appropriate health azoles (or itraconazole) and the halcinonidedcorten of 3-4 hour trace in blood sample.
Discuss: from above-mentioned experimental result, the firm skin permeation tissue of coating 1-2 hour medicine, existing trace drug enters blood circulation in the time of the 3rd hour, and the drug level that entered blood circulation in 4-5 hour does not increase.Show ointment formulation of the present invention in use, major part is only absorbed by skin histology and brings into play its therapeutical effect, and the amount that enters blood circulation is minimum, thereby general action can not take place.Test example 2 clinical observation on the therapeutic effect
Through behind preclinical every animal experiment, for being applied to clinical experiment, observes by non-standard preparation through Beijing Military Area Command's logistics Ministry of Public Health approval.Ointment formulation of the present invention is applied to General Hospital of Beijing Military Command, Shenyang medical officer hospital general, Tianjin civilian hospital, 81 division hospitals and the court's 1000 multiple-cases and uses, total cure rate 94.2%, and total effective rate reaches 99.95%.There are tinea cruris, tinea corporis, tinea manus and pedis, contact dermatitis, neurodermatitis, insect dermatitis, eczema, folliculitis, cutaneous Candida etc. all to receive excellent curative in the case of using.Use in the control experiment of ointment formulation product of the present invention and other similar medicines, ointment formulation of the present invention embodies characteristics such as healing time weak point, curative effect height.Ointment formulation of the present invention is subjected to the welcome of vast dermatosis patient deeply.What describe below is the part clinical test results that ointment formulation carried out of using the embodiment of the invention 1.One, patient and method
Patient is department of dermatologry outpatient service and inpatient, diseases such as tinea corporis, tinea cruris, eczema, dermatosis and impetigo is arranged, totally 18 kind of 982 example.Trial drug is the ointment formulation that the embodiment of the invention 1 makes.In the process of the test various tinea are carried out the fungus inspection, part has been done the test tube cultivation, turns out to be the fungoid tinea.Disease time is minimum to be 3 days, and the longest is 1 year, is generally 1-6 month, have the time heavy when light, but symptom all is apparent in view when going to a doctor.
Therapeutic Method: ointment formulation of the present invention is directly embrocated affected part, suitably rubs gently, do not wrap up, every day secondary, continuous application.
(1) to the treatment of fungoid tinea
100 patients that suffer from the fungoid tinea are divided into 50 every group test group and contrast
Group, the test group ointment formulation of the embodiment of the invention 1; Matched group compound recipe benzene first
Aching and limp cream;
(2) to the treatment of eczematous dermatitis
100 patients that suffer from eczematous dermatitis are divided into 50 every group test group and contrast
Group, the test group ointment formulation of the embodiment of the invention 1; Matched group 2% fluocinonide
Ointment;
(3) to the treatment of bacterial infection superficial part pyoderma
50 patients that suffer from bacterial infection superficial part pyoderma are divided into 25 every group examination
Test group and matched group, the test group ointment formulation of the embodiment of the invention 1; Matched group
Use 1% erythromycin ointment;
(4) to the treatment of eczematous dermatitis
50 patients that suffer from eczematous dermatitis are divided into 25 every group test group and contrast
Group, the test group ointment formulation of the embodiment of the invention 1; Matched group is real with the present invention
Execute the substrate of the ointment formulation of example 1.Two, therapeutic outcome
Criterion of therapeutical effect: (one) cures: erythra and subjective symptoms complete obiteration; (2) produce effects: skin lesion disappears more than 80%, and subjective symptoms is clearly better or disappears; (3) progressive: erythra and subjective symptoms are all than taking a favorable turn before the treatment; (4) invalid: skin lesion and subjective symptoms all do not have improvement.Control in 982 examples by this standard, cure 926 examples and account for 94.29%, produce effects 35 examples, effective 21 examples, the nonresponder does not have, total effective rate 100%.
Treatment time: different according to sick kind and state of an illness weight, the longest 35 days, the shortest 6 days.Tinea cruris, tinea corporis, scrotum tinea, dermatocandidiasis and insect dermatitis, the overwhelming majority can both be cured, and minority is a produce effects, its healing time 6-14 days, average 9 days; The tinea manuum 20 days; Tinea pedis 25 days; Eczema 23 days; Contact dermatitis 7 days; Impetigo 6 days.Do not find untoward reaction in therapeutic process, part patient visits, and cures and does not see recurrence in back three months.Three, observation of curative effect
Case example number healing produce effects is effective
Tinea cruris 156 154 2
Tinea corporis 146 144 2
Tinea manus and pedis 142 127 10 5
Dermatocandidiasis 12 12
Contact dermatitis 148 145 12
Solar dermatitis 36 34 2
Atoipc dermatitis 16 16
Insect dermatitis 33 33
Eczema 189 174 12 3
Impetigo 45 45
Folliculitis 36 27 9
Eczema infects 23 15 62 and adds up to 982 926 40 16 controlled observation tables
More than by embodiment and the test example describe the present invention.But it should be understood that those of ordinary skill in the art under the prerequisite that does not depart from spirit of the present invention and essence, can carry out various improvement and variation the present invention.
Claims (4)
1, a kind of ointment formulation that can be used for the treatment of the various skin disease, said preparation is made up of active component and substrate, it is characterized in that, and described active component is by triumphant appropriate health azoles or the itraconazole of 50-70% (weight); The polygynax of the halcinonidedcorten of 5-15% (weight) and 25-40% (weight) is formed; Described substrate is by the stearic acid of 10-15% (weight); The vaseline of 5-15% (weight); The tween 80 of 2-5% (weight); The glyceryl monostearate of 5-10% (weight); The liquid paraffin of 2-5% (weight) and the distilled water of surplus are formed, and the weight ratio of described active component and described substrate is 1-3: 99-97.
2, ointment formulation as claimed in claim 1 is characterized in that, described active component is by triumphant appropriate health azoles or the itraconazole of 55-65% (weight); The polygynax of the halcinonidedcorten 28-35% (weight) of 6-12% (weight) is formed; Described substrate is by the stearic acid of 12-14% (weight); The vaseline of 8-12% (weight); The tween 80 of 3-4% (weight); The glyceryl monostearate of 7-8% (weight); The liquid paraffin of 3-4% (weight) and the distilled water of surplus are formed, and the weight ratio of described active component and described substrate is 1.5-2.5: 98.5-97.5.
3, ointment formulation as claimed in claim 1 is characterized in that, described preparation is the oil-in-water type ointment formulation.
4, the preparation method of the described ointment formulation of claim 1 may further comprise the steps:
(1) stearic acid, vaseline, glyceryl monostearate and liquid paraffin are joined in the container mixing and stirring under 70-75 ℃ temperature; Tween 80 and distilled water are joined in the container mixing and stirring under 70-75 ℃ temperature; Temperature is remained on 70-75 ℃, stir down, the mixed liquor of tween 80 and distilled water is joined in the mixed liquor of stearic acid, vaseline, glyceryl monostearate and liquid paraffin, stir, obtain substrate after the condensation;
(2) triumphant appropriate health azoles or itraconazole, halcinonidedcorten and polygynax are ground into fine powder respectively; Then, at first triumphant appropriate health azoles or itraconazole fine powder are joined in the mortar, add the substrate that an amount of above-mentioned steps (1) obtains again and grind well, and then add halcinonidedcorten successively, polygynax, add whole substrate mixing by the dilution method that progressively increases and grind well, mix.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00100634 CN1103218C (en) | 2000-01-25 | 2000-01-25 | Ointment for treating dermatosis and its preparation |
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|---|---|---|---|
| CN 00100634 CN1103218C (en) | 2000-01-25 | 2000-01-25 | Ointment for treating dermatosis and its preparation |
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| CN1306823A true CN1306823A (en) | 2001-08-08 |
| CN1103218C CN1103218C (en) | 2003-03-19 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101623297B (en) * | 2009-05-07 | 2012-07-04 | 刘太平 | Medicine for treating beriberi |
| CN101040837B (en) * | 2006-08-21 | 2012-08-29 | 沈阳药科大学 | Itracomazole cream and the method for preparing the same |
| CN105169462A (en) * | 2015-10-22 | 2015-12-23 | 江苏科技大学 | Mixing method for improving dispersion uniformity of neomycin sulfate in vaseline |
-
2000
- 2000-01-25 CN CN 00100634 patent/CN1103218C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101040837B (en) * | 2006-08-21 | 2012-08-29 | 沈阳药科大学 | Itracomazole cream and the method for preparing the same |
| CN101623297B (en) * | 2009-05-07 | 2012-07-04 | 刘太平 | Medicine for treating beriberi |
| CN105169462A (en) * | 2015-10-22 | 2015-12-23 | 江苏科技大学 | Mixing method for improving dispersion uniformity of neomycin sulfate in vaseline |
| CN105169462B (en) * | 2015-10-22 | 2017-10-17 | 江苏科技大学 | Improve the mixed method of neomycinsulphate dispersing uniformity in vaseline |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1103218C (en) | 2003-03-19 |
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