CN1879661A - Application of nocardia rubra cell wall skeleton in preparation of medicine for resisting fungal infection - Google Patents

Application of nocardia rubra cell wall skeleton in preparation of medicine for resisting fungal infection Download PDF

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CN1879661A
CN1879661A CNA2005100774075A CN200510077407A CN1879661A CN 1879661 A CN1879661 A CN 1879661A CN A2005100774075 A CNA2005100774075 A CN A2005100774075A CN 200510077407 A CN200510077407 A CN 200510077407A CN 1879661 A CN1879661 A CN 1879661A
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medicine
cell wall
wall skeleton
nocardia rubra
disease
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CN1879661B (en
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张策
张轶
洪晓明
张国英
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Liaoning Tian'an Biopharmaceutical Co ltd
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Shenyang Sunbellcom Bio Pharmaceutical Co Ltd
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Abstract

The invention relates to application of nocardia rubra cell wall skeleton in preparing a medicament for resisting diseases caused by fungal infection. In particular to the application of the nocardia rubra cell wall skeleton (Nr-CWS) in preparing medicaments for resisting candida albicans infection. The medicine obtained by the invention can be used for local administration, and is preferably used as a liniment.

Description

The purposes of Lyopgized Nocardia rubra-cell Wall Skeleton in the medicine of preparation anti-fungal infection
Technical field
The present invention relates to the purposes of Lyopgized Nocardia rubra-cell Wall Skeleton (Nr-CWS) in the medicine of preparation anti-fungal infection, particularly relate to the purposes of Lyopgized Nocardia rubra-cell Wall Skeleton (Nr-CWS) in the medicine that the preparation anti-candida albicans infects.
Background technology
Candida albicans (claiming candidiasis again) is a kind of natural saprophytic bacteria that extensively is present in, the normal parasitic flora that belongs to human body, it is a kind of conditioned pathogen, descends or is subjected under the influence of some factor at immune function of human body, and parasitic Candida albicans can produce pathogenic and cause disease.Candidiasis is a kind of two-way fungus, have yeast mutually and mycelia mutually, be the yeast phase when parasitism, generally no pathogenicity has pathogenic mycelia phase but can change into when certain condition.Candida albicans almost can infect any tissue of body and organ, can cause multiple disease: disease that the infection oral cavity causes such as thrush, glossitis, cheilitis etc.; Infect genitals and cause candidal vulvovaginitis, candidal balanoposthitis etc.; The candidal intertrigo that skin infection causes, monilia granuloma, chronic skin mucosa candidiasis; Infection bronchus, pulmonary cause bronchitis, pneumonia, pleuritis etc.; Infect digestive tract and cause various gastrointestinal candidiasises; Can cause candidiasis septicemia, candidiasis endocarditis, candidal meningitis or the like multiple disease in addition.Cause that the low and antifungal drug of immunocompetence tolerates the disease that monilial infection is caused and shows effect repeatedly because the candidiasis patient takes various antibiotic in a large number, lack effective ideal medicine and Therapeutic Method at present clinically.
Amphotericin B (amphotericin B) is the common anti-deep fungal medicine of polyenoid class, and it has powerful inhibitory action to Candida albicans, and high concentration has bactericidal action.Absorb but it is oral, intramuscular injection is all difficult, the intravenous drip untoward reaction is more, and modal is the beginning or the back a few hours of instiling can shiver with cold, hyperpyrexia, headache, nausea and vomiting of instiling.Its nephrotoxicity is dose dependent, and azotemia takes place about 80% patient, and share nephrotoxicity with aminoglycosides, ciclosporin increases.Nystatin (nystatin) also belongs to the polyene antifungal medicine, and its physiological disposition and antibacterial action and amphotericin B are basic identical, orally is used to prevent and treat gastrointestinal candidiasis, and local application is effective to oral cavity, skin, vaginal candidiasis.But toxicity is bigger, heavy dose of oral nausea,vomiting,diarrhea that causes.Local application's zest is little, indivedual visible leucorrhoea grow in quantity of vagina medicinal.
Imidazoles antifungal agent (imidazoles) is synthetic antifungal agent.Antibacterial action is similar to amphotericin, but it has the toxicity that causes anemia, gastrointestinal reaction, erythra etc.(clotrimazole) has antibacterial action to most of funguses as clotrimazole, to the too late amphotericin B of deep fungal effect.Oral absorption is poor, and successive administration is because the liver drug enzyme inducing action can make blood drug level reduce.Untoward reaction sees that only the part is used for the treatment of superficial mycosis or Mucocutaneous monilial infection at present more.Miconazole (miconazole) antimicrobial spectrum and antimicrbial power and clotrimazole are basic identical.Oral absorption is poor, and bioavailability is low, and is about 25%~30%, and is difficult for seeing through blood brain barrier.But intravenously administrable hyperamization bolt phlebitis in addition, also have to be felt sick, vomiting, anaphylaxis etc.The concrete dosage of clinical practice should be different with pathogenic fungi.Ketoconazole (ketoconazole) is the broad-spectrum antifungal medicine.Candidiasis and the shallow tinea bacterium of table there is powerful antimicrbial power.But with gastrointestinal reaction, serum transaminase raises, and idol has untoward reaction such as serious liver toxicity and anaphylaxis.Fluconazol (fluconazole) is the broad-spectrum antifungal medicine, and antimicrobial spectrum is close with ketoconazole, but slight digestive system reaction, anaphylaxis, untoward reaction such as headache, dizziness, insomnia are arranged.
Flucytosine (flurocytosine) has higher antibacterial activity to cryptococcus, candidiasis and Pseudosaccharomycetes etc., being used for candidiasis and cryptococcus clinically infects, but easily produce drug resistance, share this product with amphotericin and enter the fungal cell and increase the performance synergism.And gastrointestinal reaction is arranged, and the property a crossed transaminase raises, and alkali phosphatase raises, untoward reaction such as leukocyte, thrombocytopenia.
Miconazole nitrate (daktarin) is the broad-spectrum antifungal medicine, and pathogenic fungus is nearly all had effect.Its mechanism is that the sterin that suppresses fungal cell membrane synthesizes, and influences permeability of cell membrane, suppresses conk, causes death.Concentration below 4 mcg/ml can suppress most of clinical isolating fungus, and wherein Cryptococcus histolyticus, candidiasis and thick pityrosporion ovale are all responsive to this medicine.Blastomyces dermatitidis and histoplasma capsulatum are extremely sensitive to this medicine, but relatively poor to the aspergillosis effect.It also has antibacterial action to golden Portugal bacterium and streptococcus and gram positive coccus and anthrax etc.Be used for cutaneous fungal infection, as the tinea manuum, tinea pedis, tinea corporis, tinea cruris.But local topical can cause erythra, rubescent, vesicle, burn feeling and the reaction of other skin irritations.And its amount of consumption of drugs is big, and it is slow to take effect, and the state of an illness easily repeatedly.For example tinea corporis, tinea cruris and tinea pedis are used ointment, lotion, each 1 time sooner or later, need at least 4 weeks of continuous use.To dermatocandidiasis, with ointment each 1 time sooner or later.If skin has rotten to the corn face, every day 2 times, need continuous 2 weeks.To tinea unguium, use emulsifiable paste, each 1 time sooner or later, continuous half a year.
Therefore, need a kind of consumption economy, instant effect makes the state of an illness not repeatedly, and non-stimulated symptom, the medicine of the novel antifungal agent, particularly anti-candida albicans that has no side effect.
Summary of the invention
The object of the present invention is to provide the new purposes of Lyopgized Nocardia rubra-cell Wall Skeleton in the medicine of preparation anti-fungal infection.The new purposes of Lyopgized Nocardia rubra-cell Wall Skeleton in the medicine that the preparation anti-candida albicans infects particularly.
Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) is a kind of nonspecific immunomodulator, by discharging the immunomodulating signal, activate the nonspecific immunity regulating system of body, improve macrophage, T cell, NK cell activity, especially the potentiation to macrophage is stronger, activatory phagocyte is eliminating pathogen rapidly, eliminate to infect, and immunity that can enhancing body.
In a preferred embodiment of the invention, the anti-fungal infection medicine of Lyopgized Nocardia rubra-cell Wall Skeleton preparation is used for the treatment of the fungus-caused disease of oral cavity infection, the fungus-caused disease of treatment genital infection, and the fungus-caused disease of skin infection etc.Being preferred for treating colpitis mycotica, cervical erosion, oral mucosa monilial infection and cutaneous Candida infects.Also be preferred for treating thrush, glossitis, cheilitis, candidiasis vulvitis, vaginitis, candidal balanoposthitis, pearl bacterium property intertrigo, monilia granuloma, chronic skin mucosa candidiasis etc.
The anti-fungal infection medicine of Lyopgized Nocardia rubra-cell Wall Skeleton preparation of the present invention can be local application, as liniment and suppository, preferably uses as liniment.Particularly, Lyopgized Nocardia rubra-cell Wall Skeleton of the present invention can add pharmaceutical carrier and make this area dosage form commonly used, as powder, lotion, tincture, liniment, oil preparation, ointment, ointment, paste, solution, face film agent, plaster, gel, aerosol etc., patch etc.
When described medicine was lotion, tincture, liniment, oil preparation, paste, aerosol, described medicine was per 1 milliliter of cell wall skeleton product that contains the described nocardia rubra of 0.001-1 milligram.
Preferably, Lyopgized Nocardia rubra-cell Wall Skeleton product of the present invention can be made freeze dried powder, for example uses the Lyopgized Nocardia rubra-cell Wall Skeleton product with pharmaceutically acceptable excipient, is preferably dextran and makes freeze dried powder.This lyophilized powder after normal saline dilution, per 1 milliliter of cell wall skeleton product that contains the described nocardia rubra of 0.001-1 milligram.
In addition, when described medicine was patch, powder, ointment, ointment, plaster, gel, face film agent, described medicine was the cell wall skeleton product that every gram medicine contains the described nocardia rubra of 0.001-1 milligram.
How preparing the disclosed pharmaceutical dosage form of the present invention is well known to a person skilled in the art.Can be referring to the relevant preparation of the preparation method of Lyopgized Nocardia rubra-cell Wall Skeleton preparation of the present invention and gained see Chinese patent No.02109258.3.
The specific embodiment
For the immunoregulation capability of verifying Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) designs following two tests: the one, " Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) is to the immunity test of mice ", through Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) mice immunized, get its peritoneal macrophage and Candida albicans co-cultivation, measure phagocytic percentage and phagocytic index and judge the activation capability of Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) macrophage; The 2nd, " Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) is to the therapeutical effect of colpitis mycotica animal model ", colpitis mycotica is mainly caused by Candida albicans, by setting up the colpitis mycotica animal model of candida albicans infection, (Nr-CWS) treats with the Lyopgized Nocardia rubra-cell Wall Skeleton preparation, with the ability of judging that its anti-candida albicans infects.
The average phagocytic percentage (74.5%) of test group is far above matched group (22.4%) in " Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) is to the immunity test of mice ", average phagocytic index (1.261) is also apparently higher than matched group (0.293), Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) activating macrophage effectively is described, improves the ability that it engulfs Candida albicans; Japan large ear rabbit with Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) treatment in " Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) is to the therapeutical effect of colpitis mycotica animal model " experiment is almost recovered behind medicine-feeding 6d, and red color visible nocardial cell wall skeleton preparation (Nr-CWS) can be resisted candida albicans infection effectively.Can prove by above two tests: Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) is activating macrophage effectively, strengthen the ability that it engulfs Candida albicans, improve the function of body opposing candida albicans infection, strengthen the immunity of body, candida albicans infection is had good immunization therapy effect.
Embodiment 1
Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) is to the immunity test of mice
One, test objective
Turnover of Mouse Peritoneal Macrophages the engulfing candida albicans of this test by being crossed by Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) immunity, proof Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) can activate the macrophage of body, and the immunity of energy enhancing body.
Two, test material
1. test medication Lyopgized Nocardia rubra-cell Wall Skeleton freeze dried powder (Nr-CWS), 60 μ g/2 milliliters, lot number: 20040701, Shenyang Shengbaokang Biopharmaceutical Co., Ltd.
2. test strain candida albicans Y01.109-001, institute of internal medicine of the Chinese Academy of Sciences.
3. experimental animal BALB/C mice, SPF level, 18-20g, Nat'l Pharmaceutical ﹠ Biological Products Control Institute, production licence: SCXK (capital) 2000-0010.
Three, test method
1. test method comes source reference " cytophagous improvement of engulfing with the sterilizing function assay method " (Chinese microbiology and Journal of Immunology) and " red nocardia rubra cell wall skeleton preparation (slave's blocking agent) immunological testing " (Science ﹠ Tech. Development Co., Chinese Medical Univ.) to formulate this test method.
2. test method introduction
2.1 employing immunological method, every batch sample be with 5 of mices, lumbar injection Lyopgized Nocardia rubra-cell Wall Skeleton preparation 20 μ g/0.2ml/ of the present invention only/time (syringe needs aseptic): immunity in 5 days is for the second time at interval.After the last immunity the 4th day, mice is killed in dislocation of cervical vertebra, Hank ' the s of lumbar injection 1/10 mice body weight gently rubbed abdominal part after 2~3 minutes, and (1.0~1.5ml) in small test tube to draw peritoneal fluid, add 4.0~5.0ml Hank ' s liquid, mixing, centrifugal 1500rpm 10min, inclining supernatant and adds 1640 nutritional solution 1.0ml, fully mixing is transferred cell number to 2 * 10 6/ ml.
2.2 matched group is except that replace the Nr-CWS other step same 3.1 with physiological saline solution
2.3 24 hours cultures of extracting waste candidiasis are made into 1 * 10 with 1640 nutritional solutions 7/ ml bacteria suspension.
Behind the Gram, count with blood counting chamber: Candida albicans is an oval, Gram-negative, but it is often inhomogeneous to dye, and about 3-5um is than the big several times of staphylococcus, the normal generation sprouts and adeciduate brood cell, so that is similar to mycelia and the pseudohypha of real non-mycelia.
2.4 cell suspension mixes with each 1.0ml of candidiasis suspension, 37 ℃ of incubators leave standstill cultivates 60min, and centrifugal 1000rpm 5min abandons liquid, and surplus about 0.3ml liquid is fully inhaled dozen mixing with capillary tube.
Mix on microscope slide 2.5 get each 1 of culture and ice-cold 0.02% U.S. blue liquid, add a cover coverslip, put 5min after, oily spectroscopy is by following formula counting.
Figure A20051007740700081
Figure A20051007740700082
(radix=do not add the natural mortality rate of the candidiasis culture of cell)
2.6 test index standard
Phagocytic rate 〉=40%
Phagocytic index 〉=0.50
3. result of the test
Observed result under the oily mirror of table 1
Figure A20051007740700091
From above result as can be known: the average phagocytic percentage (74.5%) of test group is far above matched group (22.4%), average phagocytic index (1.261) is also apparently higher than matched group (0.293), and the phagocytic activity of its peritoneal macrophage of mice that immunity is crossed through Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) obviously improves.And in field of microscope in the test group macrophage and the macrophage number that expands obviously more than matched group.
Embodiment 2
Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) is to the therapeutical effect of colpitis mycotica animal model
One, test objective
Set up the colpitis mycotica animal model with the treatment curative effect of checking Lyopgized Nocardia rubra-cell Wall Skeleton preparation (Nr-CWS) to the colpitis mycotica animal.
Two, test material
1. test medication Lyopgized Nocardia rubra-cell Wall Skeleton preparation, 60 μ g/ bottles, lot number: 20040701, Shenyang Shengbaokang Biopharmaceutical Co., Ltd.
2. positive control drug daktarin suppository, the 200mg/ grain, lot number: 041024753, Xian-Janssen Pharmaceutical Ltd..
3. the big ear various schools of thinkers rabbit of experimental animal Japan, regular grade, female, 2-2.5kg.
4. institute of internal medicine of the test strain candida albicans Y01:109-005 Chinese Academy of Sciences.
Three, method
1. test method comes source reference " the fluconazol gel is to the therapeutical effect of animal colpitis mycotica model " (Shandong medical industry " 2000 years the 19th the 4th phases of volume) and " laboratory animal and animal experiment technique " (Miao Mingsan chief editor, China Traditional Chinese Medicine Publishing House) to formulate this test method
2. the experimental technique introduction is anaesthetized rabbit with ether by inhalation, is fixed on the rabbit fixing head.Vaginal dilation is inoculated candida albicans respectively with Inoculating needle reuse inoculating loop earlier in vagina 2-4cm place, and continuous two days, in doing vaginal smear examination in postvaccinal the 3rd day for the second time, be positive, prove the modeling success.Administration as follows: No. 1 positive controls: a 20mg/ daktarin, No. 2 matched groups: use the normal saline lavation, No. 3 model control group: do not treat, No. 4 test group: 60 μ g Lyopgized Nocardia rubra-cell Wall Skeleton preparations/only, No. 5 test group: 20 μ g Lyopgized Nocardia rubra-cell Wall Skeleton preparations/only, and No. 6 test group: 6 μ g Lyopgized Nocardia rubra-cell Wall Skeleton preparations/only.Continuously medicine-feeding 6 days of test group, daktarin group successive administration 7 days was done one time vaginal smear examination in per two days.Dosage converts according to " animal experiment method " correlation formula of Sun Jingfang chief editor.
3. animal feeding environment common lab, 10 ℃ of average room temperature, feedstuff is the plain particles feedstuff.
4. curative effect determinate standard is formulated with reference to " the clinical and preclinical study guideline compilation of new drug (Western medicine) " page 5 3.3.2.7.
Recovery from illness: symptom, sign lab testing and four of etiological examinations all recover normal;
Produce effects: the state of an illness is clearly better, but has one in above-mentioned four for recovering normal fully:
Progressive: the state of an illness takes a turn for the better to some extent after the medication, but obvious inadequately:
Invalid: medication after 72 hours the state of an illness do not have obvious progress or the person of increasing the weight of arranged.
Four, result of the test
Table 1 perusal pathological changes situation
Annotate :-: recovery from illness ,+: mild hyperaemia, a small amount of secretions, ++: moderate hyperemia, edema, secretions are more, +++: severe hyperemia, a large amount of secretions of edema.
Table 2 vaginal smear examination candidiasis situation
Figure A20051007740700121
By the above two visible daktarin groups of table and three test group medication after 4 days the state of an illness had and be clearly better, recovered normally substantially in the 6th day.Also do not see the sign that the candidiasis recurrence is arranged by the 8th day, the normal saline group is progressive to some extent, the model control group no change.
Inoculation back microscopy finds that inflammatory cell exists, inflammatory cell showed increased after medicine-feeding, and observe the phenomenon of engulfing pathogen, show that the Lyopgized Nocardia rubra-cell Wall Skeleton preparation can have stronger transfer and activate cytophagous ability.
By last table as can be seen: the curative effect of 3 dosage groups of Lyopgized Nocardia rubra-cell Wall Skeleton preparation is basic identical, illustrates that various dose is basic identical on the cytophagous ability of activation, there is no dose-dependent phenomenon.
It below is the immunization therapy clinical observation that Lyopgized Nocardia rubra-cell Wall Skeleton preparation anti-candida albicans is infected.
The applicant is according to the experience of nocardia rubra preparation clinical treatment cervical erosion, with and the control effect and mechanism of unique immunization therapy, and, selected some candida albicans infection cases to carry out the clinical observation of nocardia rubra preparation for treating with reference to the animal model experiment result.Select nine cases of suffering from different candida albicans infections altogether before and after in the test, adopted red promise blocking agent (60 μ g/2 milliliter) treatment all to obtain 100% desirable curative effect.Thereby illustrate: the immunization therapy effect that nocardia rubra preparation anti-candida albicans infects, not only from the test of pesticide effectiveness susceptible of proof of standard, and can be from susceptible of proof on the animal model test of science, finally treat in the observation and also be confirmed the many cases human clinical.Form confirmation mutually.
Embodiment 3 Lyopgized Nocardia rubra-cell Wall Skeleton preparation for treating oral mucosa monilial infections
Case 1:38 year, the woman, there is the fritter white ulcer surface that is dispersed in the Sublingual, burn feeling is arranged.
After clinical diagnosis, be diagnosed as the oral mucosa monilial infection.With normal saline dilution Lyopgized Nocardia rubra-cell Wall Skeleton preparation, and soak into cotton balls, attach the affected part, oral cavity.
Each attaching 40-60 minute, each is added medicine to once sooner or later, each liniment (10 μ g/2 milliliter).
Pain relief after the medication 2 times; 4 recoveries from illness of medication.
Case 2:69 year, the man, the chemicotherapy patient, there are white ulcer surface two fritters that are dispersed in buccal, a left side, oral cavity, burn feeling, xerostomia is arranged.
After clinical diagnosis, be diagnosed as the oral mucosa monilial infection.With normal saline dilution Lyopgized Nocardia rubra-cell Wall Skeleton preparation, and soak into cotton balls, attach the affected part, oral cavity.
Each attaching 40-60 minute, each is added medicine to once sooner or later, each one (1 μ g/2 milliliter).
After the medication 3 times, affected part pain is eliminated; Recovery from illness after the medication 6 times.
Case 3:65 year, the woman, the chemicotherapy patient, ulcer place, right buccal, oral cavity adularescent speckle has burning pain, xerostomia.
After clinical diagnosis, be diagnosed as the oral mucosa monilial infection.With normal saline dilution Lyopgized Nocardia rubra-cell Wall Skeleton preparation, and soak into cotton balls, attach the affected part, oral cavity.
Each attaching was taken out after 40-60 minute, and each adds medicine to once each one (600 μ g/2 milliliter) sooner or later to use the aerosol that contains the Lyopgized Nocardia rubra-cell Wall Skeleton product.
Pain relief after the medication 3 times; Recovery from illness after the medication 5 times.
Embodiment 4 Lyopgized Nocardia rubra-cell Wall Skeleton preparation for treating cutaneous Candidas infect
In case 4:67 year, the woman after the chemicotherapy, because of weak long-term bed, causes skin of back erythema ulcer shape.After clinical diagnosis, be diagnosed as cutaneous Candida and infect.
Clean the affected part with normal saline before the medication, and, soak into cotton cloth again, be attached to the affected part and take off after 24 hours with normal saline dilution Lyopgized Nocardia rubra-cell Wall Skeleton preparation.
Every one day, reuse was with quadrat method coated red nocardial cell wall skeleton unguentum, each one (the every gram of 1mg/).
Skin condition of illness is clearly better after 3 times; After with 2 medicines, cure reinstatement fully.
Case 5:73 year, the man, behind the chemicotherapy, the red and swollen ulcer of external orifice of urethra.
After clinical diagnosis, be diagnosed as cutaneous Candida and infect.Use the medicine-feeding of Lyopgized Nocardia rubra-cell Wall Skeleton preparation liniment wound surface, will soak absorbent liquor ball and be torn into lamellar attaching affected part, and take off after attached 30 minutes with the interim bag of gauze, short its wound song absorbs medicinal liquid.
Sooner or later each treatment is once used the Lyopgized Nocardia rubra-cell Wall Skeleton preparation of the present invention of 1 mcg/ml at every turn, fully recovers after treat 6 times.
Embodiment 5 Lyopgized Nocardia rubra-cell Wall Skeleton preparation for treating colpitis mycoticas
In case 6:23 year, the woman does not educate, disease: the vaginal secretions amount is big, white bean curd slag specimen, and cervical erosion is arranged.After clinical diagnosis, be diagnosed as colpitis mycotica.
Treatment: clean vagina and cervix uteri with normal saline earlier before the medication, use Lyopgized Nocardia rubra-cell Wall Skeleton preparation liniment, 2 days last medicines are added medicine to two at every turn, and promptly cervix uteri attaches with soaking medicine magnetic tape trailer cotton balls, and vagina is placed and soaked the absorbent cotton bar.Patient takes out voluntarily after 24 hours.
Require patient to forbid sexual life in the treatment.
Medication begins for 2 times to take a turn for the better; After the medication 6 times, mycete is turned out cloudy, and cervical erosion is clearly better;
Reuse medicine 3 times only applies the Lyopgized Nocardia rubra-cell Wall Skeleton preparation of 50 mcg/ml at cervix uteri, fully recover until cervical erosion.
In case 7:22 year, the woman does not educate, disease: the vaginal secretions amount is big, white bean curd scoriform, and cervical erosion is arranged.After clinical diagnosis, be diagnosed as colpitis mycotica.
Treatment: clean vagina and cervix uteri with normal saline earlier before the medication, use Lyopgized Nocardia rubra-cell Wall Skeleton 2 day last time of preparation, each last 2.Be that cervix uteri attaches with soaking medicine magnetic tape trailer cotton balls, vagina is placed and is soaked the absorbent cotton bar.Patient takes out voluntarily after 24 hours.
Require patient to forbid sexual life in the treatment.
Therapeutic process medial vagina secretions amount reduces, and white annesl Huang, flavor alleviate.
After the medication 6 times, on inspection, mycete is turned out cloudy, and cervical erosion turns for the better by and large.
Suggestion is single with cervix uteri medicine-feeding 3 times, each Lyopgized Nocardia rubra-cell Wall Skeleton preparation (100 mcg/ml).Cervical erosion is cured.
In case 8:28 year, the woman does not educate, disease: vaginal secretions is unusual, white bean curd slag specimen.After clinical diagnosis, be diagnosed as colpitis mycotica.
Treatment: clean vagina with normal saline earlier before the medication, use Lyopgized Nocardia rubra-cell Wall Skeleton preparation liniment, added medicine to once each last 1 in 2 days.Vagina is placed and is soaked the absorbent cotton bar.Patient takes out voluntarily after 24 hours.
After 3 of the medications, symptom takes a turn for the better; After 6 of the medications, secretions is become a full member often.
Check: mycete is turned out cloudy.
In case 9:26 year, the woman does not educate, disease: vaginal secretions is unusual, white bean curd scoriform.After clinical diagnosis, be diagnosed as colpitis mycotica.
Treatment: clean vagina with normal saline before the medication, use the Lyopgized Nocardia rubra-cell Wall Skeleton preparation for treating, added medicine to once in 2 days, each last 1 Lyopgized Nocardia rubra-cell Wall Skeleton preparation (500 mcg/ml).Place vagina with soaking the absorbent cotton bar, patient takes out voluntarily after 24 hours.
Begin after 4 of the medications to take a turn for the better; After 8 of the medications, secretions is become a full member often.
Check: mycete is turned out cloudy.
Prove fully that below the Lyopgized Nocardia rubra-cell Wall Skeleton preparation has good anti-candida albicans infection immunity therapeutical effect,, all can obtain 100% curative effect as long as symptomatic treatment is adhered to standardized drug, and non-stimulated symptom, have no side effect.The Lyopgized Nocardia rubra-cell Wall Skeleton preparation has become a biological medicine of new antifungal.For the treatment candida albicans infection provides brand-new immunization therapy new method.
Although described certain preferred embodiments of the present invention, those skilled in the art should understand that these embodiments are not restrictive, the present invention is not limited to any specific embodiment, because the improvement that may also have, and without doubt, the people who knows the related field of the present invention can expect other embodiments of principle of the present invention.Therefore, scope of the present invention contains with the intention of the essence in the claim, spirit and scope.

Claims (10)

1. the purposes of Lyopgized Nocardia rubra-cell Wall Skeleton in the medicine of the disease that preparation opposing fungal infection causes.
2. purposes according to claim 1, wherein said fungus are Candida albicans.
3. purposes according to claim 1, wherein said disease comprise the fungus-caused disease of oral cavity infection, the fungus-caused disease of genital infection, and the fungus-caused disease of skin infection.
4. purposes according to claim 1 and 2, wherein said disease are that disease and the cutaneous Candida that colpitis mycotica, oral mucosa monilial infection cause infects the disease that causes.
5. purposes according to claim 3, wherein said disease are thrush, glossitis, cheilitis, candidiasis vulvitis, vaginitis, candidal balanoposthitis, pearl bacterium property intertrigo, monilia granuloma, chronic skin mucosa candidiasis.
6. purposes according to claim 1 and 2, wherein said medicine are topical drug.
7. purposes according to claim 6, wherein said medicine are patch, powder, ointment, ointment, plaster, gel, face film agent.
8. purposes according to claim 6, wherein said medicine also comprises lotion, tincture, liniment, oil preparation, paste, aerosol.
9. purposes according to claim 8, wherein said medicine are per 1 milliliter of cell wall skeleton products that contains the described nocardia rubra of 0.001-1 milligram.
10. purposes according to claim 7, wherein said medicine are the cell wall skeleton products that every gram medicine contains the described nocardia rubra of 0.001-1 milligram.
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US8460722B2 (en) 2005-09-23 2013-06-11 Shenyang Sun Bell Com Bio-Pharmaceutical Co., Ltd Use of Nocardia rubra cell wall skeleton in the preparation of anti-HPV infection medicaments
CN108295095A (en) * 2017-01-11 2018-07-20 福建省山河药业有限公司 Purposes and its drug/composite skin care product of the Lyopgized Nocardia rubra-cell Wall Skeleton in the drug/skin care item for preparing treatment acne
CN108795860A (en) * 2017-05-03 2018-11-13 辽宁格瑞仕特生物制药有限公司 Lyopgized Nocardia rubra-cell Wall Skeleton is as CD8+The purposes of T cell enhancer of proliferation
WO2020143393A1 (en) * 2019-01-09 2020-07-16 辽宁格瑞仕特生物制药有限公司 Use of red nocardia cell wall skeleton for preparing pharmaceutical for treating lichen planus
WO2020143397A1 (en) * 2019-01-09 2020-07-16 辽宁格瑞仕特生物制药有限公司 Use of nocardia rubra cell wall skeleton in treatment of recurrent aphthous ulcer
WO2020182180A1 (en) * 2019-03-14 2020-09-17 辽宁格瑞仕特生物制药有限公司 Use of rhodococcus ruber product in treatment of vulvar white lesions
CN111727236A (en) * 2019-01-15 2020-09-29 辽宁格瑞仕特生物制药有限公司 Use of Rhodococcus ruber products for treating diseases caused by Candida albicans infection
WO2020216283A1 (en) 2019-04-24 2020-10-29 辽宁格瑞仕特生物制药有限公司 Use of nocardia rubra cell wall skeleton in treatment of thermal injury
WO2021147900A1 (en) 2020-01-21 2021-07-29 辽宁格瑞仕特生物制药有限公司 Use of nocardia rubra cell wall skeleton in regenerative medicine

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8460722B2 (en) 2005-09-23 2013-06-11 Shenyang Sun Bell Com Bio-Pharmaceutical Co., Ltd Use of Nocardia rubra cell wall skeleton in the preparation of anti-HPV infection medicaments
CN108295095A (en) * 2017-01-11 2018-07-20 福建省山河药业有限公司 Purposes and its drug/composite skin care product of the Lyopgized Nocardia rubra-cell Wall Skeleton in the drug/skin care item for preparing treatment acne
CN108795860A (en) * 2017-05-03 2018-11-13 辽宁格瑞仕特生物制药有限公司 Lyopgized Nocardia rubra-cell Wall Skeleton is as CD8+The purposes of T cell enhancer of proliferation
WO2020143393A1 (en) * 2019-01-09 2020-07-16 辽宁格瑞仕特生物制药有限公司 Use of red nocardia cell wall skeleton for preparing pharmaceutical for treating lichen planus
WO2020143397A1 (en) * 2019-01-09 2020-07-16 辽宁格瑞仕特生物制药有限公司 Use of nocardia rubra cell wall skeleton in treatment of recurrent aphthous ulcer
CN111741759A (en) * 2019-01-09 2020-10-02 辽宁格瑞仕特生物制药有限公司 Use of nocardia rubra cell wall skeleton in preparation of medicine for treating lichen planus
CN111683670A (en) * 2019-01-09 2020-09-18 辽宁格瑞仕特生物制药有限公司 Use of nocardia rubra cell wall skeleton in treatment of recurrent aphthous ulcers
CN111727235A (en) * 2019-01-15 2020-09-29 辽宁格瑞仕特生物制药有限公司 Rhodococcus ruber product and pharmaceutical use thereof
CN111727236A (en) * 2019-01-15 2020-09-29 辽宁格瑞仕特生物制药有限公司 Use of Rhodococcus ruber products for treating diseases caused by Candida albicans infection
JP2022516983A (en) * 2019-01-15 2022-03-03 ▲遼▼▲寧▼格瑞仕特生物制▲藥▼有限公司 Rhodococcus louver products and their pharmaceutical use
EP3913045A4 (en) * 2019-01-15 2022-12-28 Liaoning Greatest Bio-Pharmaceutical Co., Ltd. Product derived from rhodococcus ruber, and pharmaceutical use thereof
CN111727235B (en) * 2019-01-15 2024-03-15 辽宁天安生物制药股份有限公司 Rhodococcus ruber product and pharmaceutical application thereof
US12102654B2 (en) 2019-01-15 2024-10-01 Liaoning Greatest Bio-Pharmaceutical Co., Ltd. Product derived from Rhodococcus ruber, and pharmaceutical use thereof
WO2020182180A1 (en) * 2019-03-14 2020-09-17 辽宁格瑞仕特生物制药有限公司 Use of rhodococcus ruber product in treatment of vulvar white lesions
WO2020216283A1 (en) 2019-04-24 2020-10-29 辽宁格瑞仕特生物制药有限公司 Use of nocardia rubra cell wall skeleton in treatment of thermal injury
WO2021147900A1 (en) 2020-01-21 2021-07-29 辽宁格瑞仕特生物制药有限公司 Use of nocardia rubra cell wall skeleton in regenerative medicine

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