CN1160055C - External-use bathing lotion with antibiotic and anti-inflammatory functions - Google Patents

Abstract

The present invention relates to external bath powder, particularly to Huafu bath powder composed of alum (hydrous aluminium potassium sulfate) as a traditional Chinese medicine, and peppermint extract (containing peppermint camphor). The bath powder can be dissolved in warm water to achieve the purposes of skin disinfection and skin sterilization through an immersion bath or a shower bath, and the bath powder is suitable for the adjuvant therapy of various skin diseases. The product performs significant sterilization action on Candida albicans, cryptococcus neoformans, sporotrichum schenckii, epidermophyton floccosum, microsporum gypseum, microsporum ferrugineum, staphylococcus aureus, staphylococcus epidermidis, escherichia coli, protei, hay bacillus and penicillium.

Description

External-use bathing lotion with antibacterial and anti-inflammation functions

A kind of external-use bathing lotion---magnificent cottonrose hibiscus bath powder with anti-inflammation, be applicable to clinical bacterial skin infections, fungal infection and various diseases associated with inflammation, particularly to skin lesion widely disease such as subacute or chronic eczema, general scratch where it itches that disease, rubescent dermatitis or eczema, pruritus, drug eruption, prurigo, pityriasis rosea, urethritis, scrotitis, vulvitis, gonorrhea and the non-gonorrhea sexuality of diffusivity are dyed, perianal dermatitis, perineal position dermatitis, eczema etc. and psoriatic stable phase and preferable curative effect is all arranged paracmasis.

China's cottonrose hibiscus bath powder is to treat one group of compound Chinese medicinal preparation that various dermatosiss inspire design according to immersion to boil water of motherland's medical use Chinese medicine or shower.Existing hundreds of years history of dipping development of motherland's medical science, some dermatosis was also produced certain obvious curative effects, but because the ingredient instability of various dippings, or because the dipping time is short, drug level is low, therapeutic effect is limited, some medicine is Diazolidinyl Urea or sensitization also, even can and cause the whole body poisoning through the skin absorption, therefore, seek the externally used antimicrobial antiinflammatory of some high-efficiency low-toxicities and bathe agent, be pharmacy worker heat subject anxious to be solved always.

The purpose of this invention is to provide a kind of antibacterial and anti-inflammation functions that has, but skin is not had toxic external-use bathing lotion, this bath agent can be used for the control of various dermatosis.

The object of the present invention is achieved like this, the Mentholum that adopts the Chinese medicine Herba Menthae or from Herba Menthae, purify and obtain, form compound preparation with Alumen again, after this two medicine ground to form powdery, be made into medicated powder according to a certain percentage, be distributed into every parcel 30～50g, face with preceding and it is dissolved with warm water, promptly can be used for dipping bath slightly after the cold, as long as the skin patient is affected part dipping bath in bath water 20～30 minutes, the effect that can receive anti-inflammation.

Alumen is a kind of conventional Chinese medicine; its composition is mainly aqueous sulfuric acid aluminum potassium; in treating skin disease often it as astringent and protective agent, because of it has vasoconstrictive and bring into play " antiinflammatory " effect, suppress sebaceous gland and sweat gland secretion and inflammation secretions is reduced and bring into play " convergence " and act on.Modern pharmacological research proves, Alumen has significant antibacterial action, golden Fructus Vitis viniferae and Bacillus proteus there is inhibitory action (test tube method), also there is obvious suppression to render a service (paper dish, flat band method) to escherichia coli, bacillus pyocyaneus, anthrax bacillus, dysentery bacterium, Bacillus typhi, paratyphoid fever bacillus, Bacillus proteus and staphylococcus, Candida albicans etc., the strongest to Streptococcus viridans, Hemolytic streptococcus, streptococcus pneumoniae, diphtheria corynebacterium effect; Cattle type Brucella, bordetella pertussis, meningococcus effect are taken second place, hemophilus influenza is not had effect (paper disk method), high concentration Alumen is to human-like (H ₃₇RV) and bacillus tuberculosis bovis inhibitory action is also arranged, research also shows, Alumen also has tangible anti-trichomonas vaginitis effect (Chinese medicine voluminous dictionary, P680), this mechanism of action of Alumen is commonly considered as because it has the effect of intensive solidifying protein, is suppressed even death thereby bacterial growth is grown.Herba Menthae or its extract Mentholum are classified as pruritus to it in treating skin disease, its blood circulation promoting and antiinflammatory, antipruritic etc. acts on now generally acknowledged.Clinical practice in antiinflammatory, antipruritic, pain relieving, alleviate edema etc., studies show that Mentholum is applied to skin because the tip sensor that excites nerve at first produces cold sensation, the sense of burning of slight thorn is arranged subsequently.This moment, skin temperature did not reduce, even slightly raise, and can slowly penetrate Intradermal, cause long hyperemia, and reflexive causes that the deep blood vessel changes, adjust the function of blood vessel, and reach therapeutical effect (Chinese medicine modern study and clinical practice, P683), experiment in vitro also confirms, Herba Menthae is to staphylococcus aureus, Staphylococcus albus, alpha streptococcus, group B streptococcus, micrococcus catarrhalis, the enteritis coccus, shigella flexneri, anthrax bacillus, diphtheria corynebacterium, Bacillus typhi, bacillus pyocyaneus, escherichia coli, Bacillus proteus, Candida albicans all has antibacterial action, research also shows, Herba Menthae is to herpes simplex virus, vaccinia virus, Semliki forest virus and mumps virus all have inhibitory action (Chinese medicine modern study and clinical practice, P683), research in recent years also shows, the Herba Menthae decoct, Mentholum is to dermatophytes such as trichophyton, trichophyton gypseum, acrothesium floccosums etc. all have inhibitory action, wherein Oleum menthae, Mentholum still has bactericidal action preferably.In addition, Oleum menthae, Mentholum also have killing action [Hu Lifang, sterilization and sterilization, 1989,6 (1): 10] to Candida albicans.This seminar also proves, Mentholum has the Transdermal absorption effect that promotes some antibacterials, can strengthen the antibacterial activity of some drugs, Herba Menthae or its extract and Alumen are formed compound preparation, its antibacterial action is strengthened mutually, and antimicrobial spectrum increases, and is used for treating for skin disease, antiphlogistic effects and antipruritic effect are obvious especially, and we are very sure through the clinical observation curative effect.

This project researcher is pressed folk prescription or compound recipe combination to kind of a medicine surplus Herba Menthae, Alumen and other ten respectively, and common skin antibacterial and fungus are studied, and experimental technique and result are as follows:

One, the antibacterial experiment of Alumen, Mentholum

(1), materials and methods

1, medicine: Alumen (aqueous sulfuric acid aluminum potassium 92%), Folium Menthae extract (containing Mentholum 99%), magnificent cottonrose hibiscus bath powder are provided by Medicines Science and Technology Development Center, Guangdong Medical College (.

2, strain: (1) penicillium; (2) penicillium chrysogenum; (3) penicillium citrinum; (4) acrothesium floccosum; (5) sporotrichum schenckii; (6) Candida albicans; (7) Cryptococcus histolyticus; (8) microsporon gypseum; (9) Microsporum ferrugineum; More than nine kinds provide by the Norman Bethune Medical University; (1) staphylococcus aureus; (11) staphylococcus epidermidis; (12) colon bacillus; (13) Bacillus proteus; (14) bacillus subtilis.Above four strains is provided by the calibrating of Ministry of Public Health pharmaceutical biological product.Slant medium preservation, standby is recovered, gone down to posterity, puts to the strain of above-mentioned reference culture.

3, culture medium: the plain agar culture medium, be used for the cultivation of antibacterial, sabouraud's agar is used for the cultivation of fungus.Add different pharmaceutical in culture medium, be used for antibacterial tests, used drug ratios, concentration are decided by requirement of experiment.

4, antibacterial tests: with the reference culture of antibacterial and fungus, be inoculated in respectively on the medicament selection flat board that contains variable concentrations, and be matched group with the plating medium that does not contain medicine.Fungus is put 26 ℃ of cultivations, and respectively at 72 hours with 1 when week observed and the record result, antibacterial was put 37 ℃ of incubators and cultivates, and observed and the record result judgement MIC at 24 hours and 72 hours.To the growth negative patient, to scrape and get its culture medium inoculated trace transferred species in not containing on the medicine flat board or on the inclined-plane, transferred species is still given birth to the elder, shows that this medicine is antibacterial, does not give birth to the elder and is sterilization.

4.1 Alumen, Mentholum list agent antibacterial tests.Make two kinds of medicines to be measured of variable concentrations and control drug (fungus---miconazole nitrate respectively, antibacterial---chloromycetin) Sha Shi slant medium and plain agar plating medium, 14 kinds of bacterium that inoculation is selected, put the incubator of corresponding humidity, the growing state of each bacterium of observed and recorded is judged the MIC of various medicines to different strains.

4.2 the antibacterial tests of the Alumen+Mentholum of different proportion compatibility, with the MIC (the judgement main reference dermatophytosis of this value is also taken into account all the other bacterial strains) of Alumen and Mentholum respectively in the ratio compatibility of 1: 1 and 5: 1,10: 1, with double concentration is starting point, the two-fold dilution becomes descending series medicine flat board and inclined-plane, and the inoculation different strains is observed the growth phenomenon.

(2), experimental result

1, Alumen, the agent of Mentholum list all have in various degree bacteriostasis to various funguses and antibacterial, see table 1 and table 2 for details.

Table 1 Mentholum antibacterial tests result

Drug level mg/ml	1.0	0.2	0.04	0.008
					Penicillium	-	-	+	+
Penicillium chrysogenum	-	-	+	+
					Penicillium citrinum	-	-	+	+
Acrothesium floccosum	-	-	+	+
					Sporotrichum schenckii	-	-	+	+
Candida albicans	-	-	+	+
					Cryptococcus histolyticus	-	-	+	+
Microsporon gypseum	-	-	+	+
					Microsporum ferrugineum	-	+	+	+
Staphylococcus aureus	-	+	+	+
					Staphylococcus epidermidis	-	-	-	+
Colon bacillus	-	-	+	+
					Bacillus proteus	-	-	+	+
Bacillus subtilis	-	-	-	+

Table 2 Alumen antibacterial tests result

Drug level mg/ml	12.5	6.25	3.125	1.56	0.78
						Penicillium	-	-	-	+	+
Penicillium chrysogenum	-	-	-	+	+
						Penicillium citrinum	-	-	-	-	+
Acrothesium floccosum	-	-	-	+	+
						Sporotrichum schenckii	-	-	+	+	+
Candida albicans	-	-	-	+	+
						Cryptococcus histolyticus	-	-	+	+	+
Microsporon gypseum	-	-	+	+	+
						Microsporum ferrugineum	-	-	+	+	+
Staphylococcus aureus	-	-	-	+	+
						Staphylococcus epidermidis	-	-	-	-	+
Colon bacillus	-	-	-	-	+
						Bacillus proteus	-	-	-	-	+
Bacillus subtilis	-	-	-	-	+

In table 1 as can be seen Alumen to the MIC of penicillium sp mushroom between 0.78～1.56mg/ml, for the MIC of deep fungal (Candida albicans, Cryptococcus histolyticus and sporotrichum schenckii) between 1.56～3.12mg/ml; And for dermatophytosis (acrothesium floccosum, microsporon gypseum, Microsporum ferrugineum) MIC is 3.125mg/ml, is 0.78mg/ml for the MIC of common bacteria (staphylococcus aureus, staphylococcus epidermidis, colon bacillus, Bacillus proteus, bacillus subtilis).The agent of Mentholum list to the MIC of penicillium sp mushroom between 0.04～0.2mg/ml; MIC to deep fungal is 0.04mg/ml; And between the MIC 0.04～0.2mg/g to dermatophytosis, between 0.008～0.2mg/ml, wherein golden Fructus Vitis viniferae tolerance is the strongest to the MIC of common bacteria.Staphylococcus epidermidis and bacillus subtilis are comparatively responsive.Control drug also shows bacteriostasis in various degree.

2, press the antifungal and the bacteria test result of the Alumen+Mentholum of different proportion compatibility use.Single agent antibacterial tests result shows: Alumen is A=3.125mg/ml to the MIC of dermatophytes, and the MIC of deep fungal and common bacteria then is lower than this value, and Mentholum is B=0.2mg/ml to the MIC of dermatophytes; MIC to other bacterial strains also is lower than this value.The A of different shares is merged use with the B of different shares, do further further investigation.

Experimental result shows, after the MIC of Alumen and Mentholum merged (3.125: 0.2) in 1: 1 ratio, MIC to the penicillium sp mushroom has reduced a multiple proportions gradient, the minimal inhibitory concentration of mixture is equivalent to 1/2nd of single agent, fungistatic effect to three kinds of dermatophytosises, mixture also has enhancing in various degree, wherein, bacteriostasis to acrothesium floccosum significantly strengthens than Alumen and the agent of Mentholum list, consumption all is reduced to 1/4th of former level, and the microsporon gypseum consumption is equivalent to 1/2nd of single agent; The Microsporum ferrugineum mixture is not shown potentiation.Mixture is basic similar to the agent of Mentholum list to the deep fungal fungistatic effect, but the Alumen consumption has reduced by 4 times.Mixture also has potentiation to the effect of common bacteria except that golden Portugal and table Portugal.The potentiation amplitude is that the more single agent of MIC reduces a dilution gradient.More single agent use also has potentiation to mixture to the effect of penicillium sp mushroom.Amplitude is that MIC reduces by 1 times.

When the ratio with Alumen rises to 5 times (5A: 1B 15.6: 0.2), mixture shows as bactericidal action to penicillium, when the amount ratio of Alumen and Mentholum is (1.95: 0.025), wherein the consumption of Alumen and single agent are used similarly, and the consumption of Mentholum reduces to original 1/4th; Mixture is 1.95: 0.025 to the MIC of acrothesium floccosum, the all more single agent of two survival doses reduces 1～2 times, have than obvious synergistic effect, but mixture is not better than 1: 1 ratio mixture to the bacteriostasis of microsporon gypseum and Microsporum ferrugineum, not obviously is better than single agent yet.Mixture was different to the bacteriostasis of three kinds of deep fungals in 5: 1, and is stronger to the Cryptococcus histolyticus effect, and the mixture consumption is equivalent to 1/4th and ten sixths of single agent consumption respectively for (1: 0.013).When analyzing 10: 1 mixture, because the Alumen ratio is too high, so also be to show as Alumen list agent effect basically to the effect of antibacterial and fungus.

Two, the antibacterial experiment of magnificent cottonrose hibiscus bath powder

According to above-mentioned test, we have carried out multifactorial orthogonal test to Alumen and Mentholum, seek the optimal proportion that this two medicine cooperates, by big quantity research and comprehensive each factorial analysis, we have found that Alumen and Mentholum are in 25～35: best results during 0.2～1 ratio proportioning, better to above-mentioned 14 kinds of antibacterial antibacterial actions, its comprehensive function has surpassed two medicines and has divided other effect, the factor of our comprehensive each side is considered, we have selected intermediary ratio to be made into magnificent cottonrose hibiscus bath powder, the ratio that is Alumen and Mentholum is with 30～32: 0.3～0.6 is the prescription foundation, we are mixed with compound preparation China cottonrose hibiscus bath powder with this ratio, carry out drug sensitive test and toxicity test again, the result is as follows:

1, the antibacterial action of magnificent cottonrose hibiscus bath powder clinical practice concentration research

Magnificent cottonrose hibiscus bath powder is dissolved in the clinical practice concentration in 4 kilograms the warm water by every parcel 30g, carried out antibacterial experiment, experimental result shows that this product has the obvious sterilization effect to following antibacterial and fungus: (1) staphylococcus aureus; (2) staphylococcus epidermidis; (3) colon bacillus; (4) Bacillus proteus; (5) bacillus subtilis; (6) penicillium; (7) penicillium chrysogenum; (8) acrothesium floccosum; (9) sporotrichum schenckii; (10) Candida albicans; (11) microsporon gypseum; (12) penicillium citrinum; (13) Cryptococcus histolyticus.

This product is invalid to Microsporum ferrugineum, but when concentration reaches 0.8%, when promptly every bag 30g is dissolved in 2kg warm water, then Microsporum ferrugineum is also had tangible bacteriostasis.

2, the bacteriostasis after magnificent cottonrose hibiscus bath powder clinical practice liquid dilutes 2 times

Magnificent cottonrose hibiscus bath powder is carried out bacteriostatic experiment by one times of clinical practice amount redilution (30g is dissolved in the 8kg warm water), the result shows, in to above-mentioned 13 kinds of effective bacterium, except that sporotrichum schenckii, microsporon gypseum, staphylococcus aureus, all the other 10 kinds of test organismss are still had significant antibacterial action.

3, the bacteriostasis after magnificent cottonrose hibiscus bath powder clinical practice liquid dilutes 4 times

China's cottonrose hibiscus bath powder still has significant bactericidal action by 4 times (30g is dissolved in 16 kilograms of warm water) of clinical practice amount dilution to Cryptococcus histolyticus, staphylococcus epidermidis, colon bacillus, Bacillus proteus, bacillus subtilis.

4, the bacteriostasis after magnificent cottonrose hibiscus bath powder clinical practice liquid dilutes 8 times

China's cottonrose hibiscus bath powder still has significant bactericidal action by 8 times (30g is dissolved in 32 kilograms of warm water) of clinical practice amount dilution to colon bacillus, Bacillus proteus.

Three, the studies on acute toxicity of magnificent cottonrose hibiscus bath powder report

China's cottonrose hibiscus bath powder to skin nonirritant and anaphylaxis, has certain zest to the skin injury place as disinfectant for external use when skin soaks, and certain local cool sense is arranged.

The test of white mice acute oral toxicity shows, give (20 every group of 40 white mice respectively with magnificent cottonrose hibiscus bath powder clinical practice amount and 15 times of concentration surpassing clinical consumption, male and female half and half) gastric infusion (0.75g/kg and 11.25g/kg), two groups 40 equal non-toxic reactions of mice of result, observe all survivals in 7 days, illustrated that this product is higher than 11.25g/kg to the oral minimum lethal dose of mice.As only being used for the external dipping bath, can think to belong to the minimum or nontoxic substantially level of toxicity.

Four, the prescription adjustment of magnificent cottonrose hibiscus bath powder

Studies show that, China's cottonrose hibiscus bath powder can add into sulfur, sulfur is pulverized and is powdery, 8～12% ratio in total amount adds in the magnificent cottonrose hibiscus bath powder, can obtain better curative effect, it is good to dermatosis curative effect spies such as scabies that this bathes agent, and further research shows that also the optimal proportion of magnificent cottonrose hibiscus bath powder is that the ratio of sulfur, Mentholum, Alumen is 2～4: 0.5: 30.

Five, the application example of magnificent cottonrose hibiscus bath powder:

Get Mentholum and Alumen etc. and pulverize, be made into magnificent cottonrose hibiscus bath powder as stated above, be distributed into every bag 30g, face with before adding stirring and dissolving in 4 kilograms of 40～50 ℃ of hot water, soak the affected part, every day one is to secondary, logotype 5～7 days, remission or disappearance such as can make skin affected part inflammation, scratch where it itches.This product is attached institute department of dermatologry clinical observation 1000 routine patients through the court, tentatively prove this product to scabies, acne, psoriasis, seborrheic dermatitis, neurodermatitis, eczema, fill the air scratch where it itches disease, pruritus, drug eruption, prurigo, pityriasis rosea, urethritis, scrotitis, vulvitis, perianal dermatitis, perineal position dermatitis, gonorrhea and gonorrhea sexuality of rubescent dermatitis, general and dye etc. significant curative effect is all arranged.Effective percentage reaches 98%.

Claims (3)

1, a kind of external-use bathing lotion with anti-inflammation is characterized in that, be made up of Mentholum and Alumen, and the optimal proportion of Mentholum and Alumen is 0.2～1: 25～35.

2, a kind of external-use bathing lotion with anti-inflammation is characterized in that, described bath agent contains bath agent as claimed in claim 1 and sulfur, and sulfur is to be ground into behind the fine powder in 8～12% ratio to add among this bath powder.

5, as claims 2 described external-use bathing lotions with anti-inflammation, it is characterized in that, is this bath agent sulfur, and the formula proportion of Mentholum and Alumen is 2～4: 0.5: 30.