CN1178664C - Remedy for axillary osmidrosis containing adrenocorticosteriodal preparation - Google Patents

Remedy for axillary osmidrosis containing adrenocorticosteriodal preparation Download PDF

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Publication number
CN1178664C
CN1178664C CNB96180582XA CN96180582A CN1178664C CN 1178664 C CN1178664 C CN 1178664C CN B96180582X A CNB96180582X A CN B96180582XA CN 96180582 A CN96180582 A CN 96180582A CN 1178664 C CN1178664 C CN 1178664C
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preparation
thalline
adrenocorticosteriodpreparation
extract
lactic acid
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CNB96180582XA
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CN1244800A (en
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山元启子
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Abstract

The present invention relates to a remedy for axillary osmidrosis, which is characterized in that the remedy for axillary osmidrosis contains an effective dose of adrenocorticosteroid compound and 1 to 10 wt% of extract of a lactic acid fermentation product for each gram of matrix. The extract generated by lactic acid fermentation comprises the metabolites of lactic acid bacteria and components containing the self-bacteria of the lactic acid bacteria. Because the secretion of odor steroid compounds which cause axillary osmidrosis is inhibited, the re-metabolism of the odor steroid compounds caused by axillary osmidrosis bacteria can not occur. In addition, the employed adrenocorticosteroid compound hardly has side effect.

Description

The osmidrosis treatment medicine that contains the adrenocorticosteriodpreparation preparation composition
Technical field
The invention relates to and use adrenocorticosteriodpreparation preparation preparation for treating bromhidrosis, particularly above-mentioned steroidal compounds mixes use with the lactate fermentation extract.
Background technology
Up to the present, the treatment bromhidrosis we make stink disappearance, antiperspirant wait the breeding environment that suppresses antibacterial by also main use deodorizer, and antibacterials such as antibiotic and antibacterial suppress methods such as bacterial activity and killing bacteria.
Epithelium steroid secretory tissues such as the apocrine gland relevant with bromhidrosis carry out various steroidal compounds metabolism and secretions such as cholesterol, gonadal hormone.
Bromhidrosis be since certain in the above said steroidal compounds the oxter adhered to by epithelium and the odorous steroidal compounds of the bacterial metabolism of breed generation due to: 5 α-rost-16-en-3-one (5 α-A).But this chemical compound itself does not detect from the secreted juice of the secretory tissue of bromhidrosis.If according to general theory, the C that the secretory tissue intracellular metabolite goes out 19Steroidal compounds be the antibacterial that adheres to by the oxter again metabolism produce.
Mainly comprise in bacterium acidi propionici, coryneform major part (coryneform bacteria) and the staphylococcus class strain that a part can the metabolism steroidal on the antibacterial that epithelium adheres to.
The method of treatment bromhidrosis mainly was usually to remove antibacterial that the oxter epithelium adheres to reach the generation that suppresses odorous steroidal by smear antibiosis in the oxter in the past.But this method can not obtain satisfied effect at short notice.Only depending on surgical management to treat bromhidrosis now can not effect a radical cure.
The present inventor has invented a kind of method that does not adopt the surgical management method and can effect a radical cure the curative of bromhidrosis rapidly.Promptly found adrenocorticosteriodpreparation preparation and as the anti-microbial type mixture of substances of adjuvant effective ways to the treatment bromhidrosis.And patent application (spy opens flat 3-66608) proposed.
The impure adrenocorticosteriodpreparation preparation that uses of osmidrosis treatment medicine in the past.Therefore it is not really clear to the concrete pharmacological action of osmidrosis treatment.Consider that bacterium acidi propionici has susceptibility to adrenocorticosteriodpreparation preparation, synthetic as one of adrenocorticosteriodpreparation preparation effect particularly to when injected organism tissue, the inhibitory action of secretion steroidal compounds can suppress to cause the excretory odorous steroidal substances of oxter epithelial tissue of bromhidrosis so consider it.
With adrenocorticosteriodpreparation preparation treatment bromhidrosis effect highly significant and rapid.According to clinical experiment situation originally, smear this product of about effective dose below 2 milligrams for several times according to symptom, can reach the effect of curing fully.But owing to worry to use steroidal substances to have side effect continuously, preferably the short time is used high concentration.But according to body constitution, when the symptom administration number of times increases, can produce side effect such as eczema, erosion and lichenificationization, and accompanying infection sometimes, so dosage is also limited.
Invention is described
The present inventor based on lactate fermentation after the metabolism product of gained lactobacillus skin is had convergence and repair, and antibacterial had suppress and killing action.After having repeated various experiments, having found to have the adrenocorticosteriodpreparation preparation and the coupling of the resulting specific generation extract of lactate fermentation of special treatment effect to bromhidrosis, can suppress the side effect of adrenocorticosteriodpreparation preparation.
That is to say, the invention provides the osmidrosis treatment medicine, it is characterized in that adding the adrenocorticosteriodpreparation preparation of effective dose and the lactate fermentation extract of 1%-10% (weight) in the 1 gram substrate.
Implement preferred plan of the present invention
For substrate, the adrenocorticosteriodpreparation preparation of 100ppm can produce significant effect to the bacterium acidi propionici that causes bromhidrosis, for the osmidrosis treatment medicine, preferably use the concentration of minimum 300ppm, even but surpassing 30000ppm (30mg/g) can not increase therapeutic effect.
Adrenocorticosteriodpreparation preparation used in the present invention, for example: prednisolone, can ground pine, hydrocortisone, general well-known adrenocorticosteriodpreparation preparations such as hydrocortisone, prednisone, methyl Bo Nisong, methyl Bo Nisonglong, omcilon, dexamethasone, 6.alpha.-fluoro-16.alpha.-methylprednisolone, betamethasone and beclometasone have all shown same effect.
On the other hand, the side effect of these adrenocorticosteriodpreparation preparations has also been reduced significantly owing to added the said lactate fermentation product in front.Though reason wherein is not fully aware of, can think that the lactate fermentation product can prevent that adrenocorticosteriodpreparation preparation from causing the side effect of infringement skin and can be suppressed at skin injury and change the back and recover the infection that just often can take place.
The scope of application of the extract that above-mentioned fermentation generates is 1% weight-10% weight with respect to substrate.The extract of 1% weight just can obtain desired effect, surpasses 10% weight if increase concentration again, will produce the strong impulse effect to skin, has influenced actual treatment.
It is the extract of lactate fermentation gained that lactate fermentation used in the present invention generates extract, particularly lactic fermentation liquid filters the fine purification of lactic acid liquid of back gained through heat sterilization and membrane filter, and is preferred as the lactic acid thalline of filtering residue by grinding the mixture from somatic cells matter extract that obtains.
In the extract that above-mentioned lactate fermentation generates, remove and to contain the metabolite (lactic acid) that thalline is discharged, also contain each seed amino acid of constituting somatic cells self, protein, nucleic acid, lipid, glycoprotein, polysaccharide etc. and mix and be called lactate fermentation generation extract.
Using various variety classes lactobacilluss by the while cultured method, in the emulative stage of development, filter out lactic acid bacteria culturers, be characteristics of the present invention.
The lactobacillus inoculation that uses among the present invention can be enumerated multiple strain, their cultural method is also varied, I (B.bulgaricus A for example, B.acidophilus 1, M.lactisacidi), II (B.bulgaricus B, B.acidophilus, M.lactisacidi), III (Kornchenbacillus A, B.acidophilus, M.lactisacidi), and IV (Kornchenbacillus B, B.acidophilus W.lactisacidi) comprises a kind of lactobacillus and lactic acid coccus at least in each group (I)~(IV), the different multiple lactobacilluss of bacterial strain carry out formerly being commissioned to train fosterly according to institute's fixed condition separately between each group, obtain each group culture and mix the back and carry out successive transfer culture more simultaneously and can obtain good result.In this case, preferably can remove former metabolism product of being commissioned to train when supporting, only thalline be carried out successive transfer culture by means such as filtrations.
The lactobacillus of above-mentioned successive transfer culture gained carries out processing such as pasteurization, the metabolism product that thalline is discharged during with cultivation filters by vacuum diaphragm, just obtained (lactic acid) the transparent filtrate of acid (pH3-4), adding on the filter membrane thalline as filtering residue again pulverizes, extraction obtain from the above-mentioned constitute in the somatic cells, just obtained lactic acid fermented generation extract.
Embodiment
Below embodiments of the invention are illustrated.
Experimental example 1
3 kilograms of 10 kilograms of defatted milk powder and glucoses add 87 kilograms in water,, are cooled to 37 ℃ and make culture medium after 60 minutes 100 ℃ of sterilizations.Inoculate the lactobacillus (Strepto thermophilus) that has obtained then, cultivated 48 hours down at 37 ℃ by other adhoc approach.Culture fluid is used diatomite filtration behind 60 ℃ of heat sterilizations, this membrane filter filtration sterilization of reuse, the fermentation lactic acid filtrate that the pH3-4 that obtains is transparent.Then, the filtering residue lactic acid thalline on the filter membrane is carried out freezing grinding, obtain extract, it is mixed obtaining the generation extract A that obtains by lactate fermentation with above-mentioned lactate buffer solution from somatic cells matter.
Experimental example 2
With I (B.bulgaricus A, B.acidophilus, M.lactisacidi), II (B.bulgaricus B, B.acidophilus, M.lactisacidi), III (Kornchenbacillus A, B.acidophilus, M.lactisacidi) and IV (Kornchenbacillus B, B.acidophilus, W.lactisacidi) wait each population separately, according to different lactobacilluss (II)-(IV) between each group, bacterial strain was cultivated 120 hours down for about 37 ℃ in mean temperature by following described culture medium.
The trypticase peptone ... 10.000g
Yeast extract ... 5.000g
Potassium phosphate ... 6.000g
The citric acid ammonium ... 2.000g
Glucose ... 20.000g
Sorbitol monooleate ... 1.000g
The hydration sodium acetate ... 25.000g
Magnesium sulfate ... 0.575g
Manganese sulfate ... 0.120g
Ferrous sulfate ... 0.034g
Agar ... 15.000g
pH5.5
The gained culture is handled with quadrat method according to embodiment 1, obtains the lactate fermentation extract B.
Experimental example 3 (bacterium acidi propionici is to the sensitivity experiment of adrenocorticosteriodpreparation preparation)
The experimental bacteria of successive transfer culture is seeded in increases bacterium, under 35 ℃ of anaerobic situations, cultivated 48 hours, culture fluid is diluted to bacterial population about 10 on culture medium increasing bacterium then with on the culture medium 6/ milliliter is transplanted to GAM Block イ ヨ Application [day water pharmacy (strain)] with a platinum circular rector thalline, cultivates 24 hours as inoculation bacterium liquid under 35 ℃ of anaerobism.
In each culture dish that contains GAM agar culture medium (day water pharmacy (strain)), inject above-mentioned bacterium liquid 15ml respectively so that the bacterium number is about 10 6/ ml.And it is fixing.Preparing the adrenocorticosteriodpreparation preparation amount that contains in the culture medium cream that is equivalent to 1 gram then is the test film of 28 milligrams of prednisolones.Simultaneously further slowly be diluted to 1-28000 doubly according to substrate cream, the test film of getting well with dilution spreads upon the sensitivity tests disk (filter paper) of 10 millimeters of diameters and places on the culture medium.According to after the fixed time cultivated, observe inhibition zone, the result is as shown in the table.From showing and can observe significantly, be that 280 times (1000ppm) beginning just can form 4 millimeters inhibition zone from extension rate, when the width of inhibition zone is W, the width that contains the inhibition zone of test film is T, when the width of test film is D, obtains following formula:
W?=?T-D/2
To the formed inhibition zone of test organisms
Test organisms bacterial concentration detection material effective ingredient result
The extension rate of (/ml) concentration (ppm)
1 28,000 +(18mm)
7 4,000 +(14mm)
Propionibacterium 4.8 * 10 628 1,000+(11mm)
280 100 +(4mm)
2,800 10 -
28,000 1 -
Experimental example 4
Can find out significantly that according to top sensitivity experimental result bacterium acidi propionici can produce tangible sensitivity for 100ppm concentration adrenocorticosteriodpreparation preparation, the above concentration of 1000ppm can reach positive effect.For the bromhidrosis patient, use the adrenocorticosteriodpreparation preparation of 300ppm to test with the lactate fermentation extract mixing gained test medication of 3% weight.
In the test, 350 patients according to once-a-day usual method, have been smeared the curative that contains in the 1 gram ointment base as prednisolone of adrenocorticosteriodpreparation preparation 0.3 milligram (300ppm) and extract A 30 milligrams (3% weight) in the oxter.The symptom of most of patients has all had improvement, because the symptom difference, after bromhidrosis alleviates or eliminates fully, still has some patient's one all left and right sides disease relapses.Prednisolone to symptom is effective to a certain degree, but is insufficient to some symptom under this coating concentration.
Experimental example 5
To other 150 bromhidrosis patients, we are that 28 milligrams (28000ppm) and 30 milligrams of mixed curatives of extract B carry out the treatment of smearing with quadrat method with the concentration that contains prednisolone in the 1 gram substrate again.Nearly all not recurrence in a very long time of these patients, and some side effect of prednisolone do not produce fully yet.
Above experiment in, side effect such as the armpit skin eczema that has 10 patients to produce to cause, erythra, erosion because treatment atopy disease when just treating bromhidrosis, is used adrenocorticosteriodpreparation preparation repeatedly.
For these patients, smear 2-4 time every day according to the symptom that produced in the experiment, there is 8 people's above-mentioned skin side-effects to have significantly and alleviates, and have 2 people to recover fully and bromhidrosis or dermatopathy do not recur so far.This 10 philtrum has 2 people not receive good effect, not administration again.
The feasibility of using on the industry
The present invention can produce significantly by administration at short notice to the underarm odor that is difficult to effect a radical cure always Curative effect, do not have the side effect of now using adrenocorticosteriodpreparation preparation to produce yet. Cause This as the methods for the treatment of of underarm odor, is effective.

Claims (3)

1. osmidrosis treatment medicine, it is characterized in that for 1 gram substrate, contain the adrenocorticosteriodpreparation preparation of effective dose and the lactate fermentation extract of 1~10% weight, wherein lactic acid fermented generation extract is meant metabolism product that thalline in the lactobacillus incubation generates and derived from the mixture of the component of thalline, wherein stating the metabolism product is to obtain by filtering from the thalline after the sterilization as the liquid filtering thing, and described component derived from thalline is to obtain by pulverizing the filtering residue that filters the thalline gained.
2. the described osmidrosis treatment medicine of claim 1, wherein containing adrenocorticosteriodpreparation preparation is the 0.3-30 milligram.
3. the described osmidrosis treatment medicine of claim 1, wherein, above-mentioned lactobacillus is to carry out respectively formerly being commissioned to train fosterly by different each groups of lactobacillus of bacterial strain between each group, each group of gained lactobacillus mixes the back and carries out the successive transfer culture gained simultaneously again.
CNB96180582XA 1996-12-10 1996-12-10 Remedy for axillary osmidrosis containing adrenocorticosteriodal preparation Expired - Fee Related CN1178664C (en)

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CNB96180582XA CN1178664C (en) 1996-12-10 1996-12-10 Remedy for axillary osmidrosis containing adrenocorticosteriodal preparation

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Application Number Priority Date Filing Date Title
CNB96180582XA CN1178664C (en) 1996-12-10 1996-12-10 Remedy for axillary osmidrosis containing adrenocorticosteriodal preparation

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CN1178664C true CN1178664C (en) 2004-12-08

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