CN1291725C - Nocardioactinomycetes cell wall skeleton preparation - Google Patents
Nocardioactinomycetes cell wall skeleton preparation Download PDFInfo
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- CN1291725C CN1291725C CNB021092583A CN02109258A CN1291725C CN 1291725 C CN1291725 C CN 1291725C CN B021092583 A CNB021092583 A CN B021092583A CN 02109258 A CN02109258 A CN 02109258A CN 1291725 C CN1291725 C CN 1291725C
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- nocardia rubra
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The present invention relates to a biological preparation, particularly to a red nocardia actinomycete cell wall skeleton preparation. Firstly, red nocardia actinomycetes CGMCC No. 0712 are cultivated through enrichment cultivation, thallus collection, cell pulverization, enzyme purification, grease removal to obtain an object, blending, filling and freeze drying, wherein the biological preparation comprises red nocardia actinomycete cell wall skeleton and dextran 40 according to a certain mixing proportion. A series of tests and clinical results show that the present invention has conspicuous curative effect on indication. The cure rate and the total effective rate of the present invention can be up to 88% and 100% respectively. The present invention has no damage to normal tissues and has the advantages of no toxicity, high safety, little side effect, simple and convenient use and low cost. The present invention replaces an inlet medicine and is a preferable externally applied medicine for treating cervical erosion.
Description
Technical field
The present invention relates to a kind of biological preparation, particularly contain the preparation of Lyopgized Nocardia rubra-cell Wall Skeleton, is the external used medicine of treatment patient first-selection.
Background technology
Cervical erosion is the modal chronic disease of gynecological, and nearly 30% the women of child-bearing age suffer from this disease, and the obvious leucorrhoea grow in quantity of the patient who has, lumbosacral aching pain and bearing down if there is inflammation the part, also purulent leukorrhea can occur, need treat.Method, described Therapeutic Method such as the domestic Therapeutic Method that adopts at present usually has that electricity is pressed, freezing, laser and microwave exist such as damaging during normal structure, the treatment vaginal secretions and roll up and be attended by stench flavor, wait one month after unsatisfactory parts such as symptom just can disappear.Simultaneously, curative effect is unsatisfactory again, also is subject to seasonal restrictions, and also should not adopt above-mentioned method treatment usually summer.From the Albothyl concentrated solution of state's import be treatment cervical erosion local topical medicine preferably, but because it costs an arm and a leg, and curative effect is not ideal enough again, makes general patient forbidding, and above-mentioned traditional method treatment is accepted in bearing affliction of can only having no way out.
Summary of the invention
In order to overcome the deficiencies in the prior art part, the object of the present invention is to provide a kind of evident in efficacy to indication, side effect is little, the part is not had the obvious stimulation symptom, do not damage normal structure, and can make vaginal secretions minimizing and doing well,improving, safety good, the medicine for external use of substituting import one easy to use, treatment cervical erosion with low cost.
In order to finish purpose of the present invention, the invention provides a kind of preparation that is used for the treatment of cervical erosion, it is characterized in that comprising the cell wall skeleton product of nocardia rubra.
Said preparation also comprises its pharmaceutically acceptable excipient, is preferably Dextran 40.
The present invention also provides a kind of method for preparing treatment cervical erosion preparation, comprise: with preserving number be the nocardia rubra of CGMCC No.0712 increase bacterium cultivate, collect thalline, cell pulverization, through DNA enzyme, RNA enzyme, pronase, tryptic purification, after the grease removal the Lyopgized Nocardia rubra-cell Wall Skeleton product;
The Lyopgized Nocardia rubra-cell Wall Skeleton product that obtains with pharmaceutically acceptable mixed with excipients, is obtained a preparation.
In the method, described pharmaceutically acceptable excipient is preferably Dextran 40.Form according to said preparation, be per 0.5 milliliter, the content of the cell wall skeleton product of described nocardia rubra is 60 micrograms.
The present invention treats the method for cervical erosion, is that the cell wall skeleton product with nocardia rubra directly spreads upon disease sites.
The microorganism that the present invention uses:
What be used for producing product of the present invention is a kind of bacterial strain that belongs under the Nocard's bacillus, and it has the ability of producing nocardia rubra cytoskeleton preparation.Nocardia rubra (Nocardiarubra) Nr-8206 (hereinafter to be referred as the Nr-8026 bacterial strain) just has above-mentioned characteristic, is suitable for producing product of the present invention.This bacterial strain is through on the glycerin agar culture medium, cultivated 5 days and get for 33 ℃, this bacterial strain on February 5th, 2002 in the common micro-organisms center preservation of Chinese microbial preservation administration committee, deposit number is: CGMCC No.0712.
The mycology feature of bacterial strain Nr-8026 bacterial strain of the present invention:
1. colony morphology characteristic
On the glycerin agar culture medium, to cultivate 48 hours for 33 ℃, the bacterium colony protuberance is Chinese red, and dry tack free purses up, and outward appearance is sand shape, and is slightly glossy.The inoculating loop contact is frangible.Microscopically is observed thalline and is that branch is dendritic a diaphragm, forms very thin mycelium.Whole mycelia splits into the short and thick cell of cylindricality of rule, cultivates 5 days thalline and becomes rod-short and sphere.
2. dyeability
Gram
Stained positive, the acid-fast stain feminine gender.
3. biochemical characteristic
Through 33 ℃, the culture of the bacterial strain of cultivating in 48 hours of the present invention is inoculated in the following various culture medium, through 33 ℃, begins observation structure after 24 hours, observes continuously 8 days on the glycerin agar slant medium, and biochemical reaction sees the following form:
The biochemical reaction result of nocardia rubra
Meeting above standard person can be used for producing
[notes] :+positive acid-feminine gender of producing
Cultivate and extracting method:
Belong to by conventional microbial production with nocardia rubra, can cultivate the Nr-8026 bacterial strain of preservation of the present invention, and through go down to posterity, amplification, ultrasonic grinding, extract obtain this cell wall skeleton, enzyme purification, organic solvent grease removal after, add an amount of excipient again after lyophilizing make.Its training method both can be solid culture, also can be liquid culture.
Nutrient source in the culture medium be there is no special regulation, can make and contain carbon source, nitrogenous source and other nutrient source that is generally used for microorganism culturing in the culture medium.Wherein carbon source can be divided into starch, dextrin, mannitol, sucrose, mannose, lactose, sorbitol, maltose, admitol etc.Nitrogenous source can be meat extract, peptone, ammonium salt, nitrate and other organic or inorganic nitrogen-containing compound.Then can suitably add some inorganic salts as for other nutrient source.For example Sal, phosphoric acid salt.
Condition of culture such as temperature, time be there is no strict restriction, be beneficial to use the growth of bacterium to be as the criterion, and to select to make the highest condition of its output for well.For example the pH value of culture medium with near neutral for well, cultivation temperature should be at 22-37 ℃, certainly the component of these culture medium, hydrogen ion concentration, cultivation temperature etc. all should be carried out suitable adjusting according to employed bacterial strain difference and external condition etc., to obtain best effect.
Method by conventional cultivating microorganism, Nr-8026 inoculation of the present invention is cultivated strain on the glycerin agar base, increase bacterium cultivation, microorganism collection, cell pulverization after behind the enzyme purification, grease removal through the strain of assay approval, be the effective ingredient cell wall skeleton product of product of the present invention, add and well known to a person skilled in the art pharmaceutical carrier, the receptible excipient of for example medicinal microorganism formulation, preferably as Dextran 40, lyophilizing is finished product after the fill.
The product of the present invention that obtains is 0.5ml for every bottle, and it forms with proportioning as follows:
Lyopgized Nocardia rubra-cell Wall Skeleton 60 micrograms (μ g)
15 milligrams of Dextran 40s (mg)
Its quality index sees the following form after testing:
| Inspection content | Touchstone | Assay |
| Physical behavior | This product is white loose body or powder | The white loose body |
| Moisture | ≤ 3% | 2.74% |
| Dissolubility | Add sodium chloride and be injected at dissolving in 1 minute | Qualified |
| The sugar discrimination test | Solution is aeruginous | Solution is aeruginous |
| 3-O-.alpha.-carboxyethyl-D-glucosamine. content | 〉=1.0 μ g/ bottles | 1.64 μ g/ bottle |
| Mice undue toxicity experiment | In the observation period, mice should all be still living and in good health, no abnormal reaction, and every the mice weight increase that expires, it is qualified to be judged to. | Qualified |
| Cavia porcellus undue toxicity experiment | In the observation period, Cavia porcellus should all be still living and in good health, no abnormal reaction, and every the Cavia porcellus weight increase that expires, it is qualified to be judged to. | Qualified |
| Render a service experiment | Phagocytic percentage: 〉=40% | Phagocytic percentage: 43.6% |
| Phagocytic index: 〉=0.20 | Phagocytic index: 0.63 | |
| Sterility test | Negative | Negative |
| Check conclusion | Qualified | |
The present invention compared with prior art; owing to be to utilize cells of microorganisms wall skeleton as effective ingredient; the biological preparation of making; this cell wall skeleton is a kind of immunostimulant; its can enhancing body antitumor action and some virus and bacterial infection is had protective effect; strengthen the phagocytic activity of macrophage and proved by a series of experiment and hospital clinical trial; indication has been obtained gratifying curative effect; cure rate reaches 88%; always reach 100%, to the normal structure not damaged with efficient; nontoxic; safety is good, and side effect is little; be a kind of efficient; safety; easy to use, the external used medicine of the treatment cervical erosion that cost is low.
Nocardia rubra Nr-8026 used in the present invention, in on February 5th, 2002 in the BeiJing ZhongGuanCun, Chinese microbial preservation administrative center contains at common little living center, accession designation number is: CGMCC No.0712, and the process detection shows the bacterial strain survival of being deposited, nothing mistake reviver.
1. general pharmacology test
1), with after being equivalent to 20,40,80 times of intravenous injections of clinical dosage, to all obviously influences of generation of anesthetized cat blood pressure, breathing, heart rate and electrocardio;
2), with after being equivalent to 1000 times of intravenous injections of clinical dosage, coordination exercise and the learning and memory function of mice do not produced tangible influence.
Thereby visible preparation of the present invention does not all have obvious influence to animal spirit, psychiatric system, cardiovascular system, respiratory system.
2. safety test (aseptic, toxicity)
1), sterility test feminine gender as a result, prove that sterility test is qualified;
2), pass through acute toxicity test in mice: experimental group is given white mice preparation of the present invention with subcutaneous injection and lumbar injection mode respectively, its dosage is 5 times of people's consumption, matched group props up substitute with physiological saline solution 0.5ml/, observed 7-8 days continuously, mice is in good condition, and body weight is all than increasing before the injection, and is all no abnormal, cut open all no abnormal variation of inspection each internal organs of mice, toxicity test is qualified.
3. long term toxicity test
To be higher than the dosage of 30 times of clinical dosages, once a day, vagina uses Canis familiaris L. preparation of the present invention three months for test continuously, do not find the toxic effect of Canis familiaris L., electrocardiogram, every blood biochemical and physiochemical indice all do not find that more all overt toxicity changes in normal range with before the administration, after two weeks of drug withdrawal, every index of Canis familiaris L. of waiting until observation is also normal, do not see the delayed toxicity reaction, thereby show preparation of the present invention, free of toxic effects in the time range at used dosage.
4. stability of drug products test
Do not have under the change situation in production technology, medicine at normal temperatures, placed 1,2,3 month, 8 months, 14 months, in the time of 21 months, the alanine that contains in the said preparation, its content of 3-O-.alpha.-carboxyethyl-D-glucosamine. were compared no significant difference with this production during this month, thereby illustrate that under such condition, stability of formulation is good; Phagocytic rate and phagocytic index when of that month has no significant change with these three batches by potency test surface again.Show that product stability is good, but room temperature was preserved 2 years after the lyophilizing.
5. immunity test
It is very capable that chicken red blood cell is engulfed in dosage surface immunity of the present invention, its phagocytic rate is 59-74.4%, phagocytic index is 0.6-0.9, and its phagocytic rate of Dextran 40 and phagocytic index are all low than normal saline, thereby illustrate that preparation of the present invention immunity phagocytic activity is very strong, and Dextran 40, normal saline there is not this effect.
The specific embodiment
With Carnis Bovis seu Bubali cream 4.0g, peptone 8.0g, sodium chloride 4.0g, agar 16.0g, glycerol 8.0ml, Na
2HPO
412H
2O 0.24g, distilled water 800ml are configured to the glycerin agar culture medium, and after the pH7.2-7.5 sterilization, with nocardia rubra Nr-8026, CGMCC No.0712 is inoculated in this culture medium, cultivate 5 days for 33 ℃; Behind the spawn culture of assay approval, be inoculated on the glycerin medium, cultivated 5 days for 33 ℃.After washing lawn with sterile distilled water, with 3000rpm centrifugalize in 20 minutes, collect thalline and wash five times, merge thalline and claim weight in wet base, put-20 ℃ of preservations through the bacterium liquid of assay approval.No varied bacteria growing person uses through the test of purification strain, get for example wet bacterium of 1 part of weight, pulverize with the ultrasonic grinding machine after vibrating with the sterile distilled water of 3 parts of weight, every pulverizing 10 minutes, remove from office blue formula dyeing microscopic examination dyeing, test under microscope is pulverized situation, and the tangible bacterium in each visual field must not surpass 6, checks that it is qualified that 30 visuals field all reach this standard.Pulverize qualified back and removed sediment in centrifugal 20 minutes with 1400rpm, supernatant-20 ℃ preservation is standby.Configuration phosphate PBS buffer solution pH 7.2-7.4.The PBS buffer solution for preparing is standby after sterilizing, pair cell wall skeleton extracts then, get supernatant 400ml and abandoned supernatant in centrifugal 20 minutes with 14000rpm, after the PBS buffer solution that precipitation and 400ml are dissolved with DNA enzyme that its concentration is 350 μ g/ml, RNA enzyme mixes, abandoned supernatant in centrifugal 20 minutes with 14000rpm after 1 hour for 22 ℃, its precipitation is washed secondary with PBS buffer solution.And check that through RNA enzyme, dnase digestion rate its precipitation is diluted to 400ml with 2% Triton X-100, and 22 ℃ after 24 hours, removed supernatant in centrifugal 20 minutes through 14000rpm, precipitate and wash secondary with PBS buffer solution.Gained precipitation is with pronase (80 μ g/ml) and trypsin 3.0mg/ml) solution dilution to 400ml, 22 ℃ after 12 hours, removed supernatant in centrifugal 20 minutes through 14000rpm, precipitation is washed secondary with PBS buffer solution.The 0.5ml that keeps sample detects the albumen residual volume.The organic solvent grease removal: on go on foot gained precipitation with acetone diluted to 400ml, 22 ℃ 24 hours, behind centrifugal 20 minutes of the 14000rpm, wash secondary with PBS buffer solution, then its gained precipitation with ether and alcoholic acid 1: 1 mixed liquor to 400ml, 22 ℃ 24 hours, 14000rpm is after centrifugal 20 minutes for usefulness, wash secondary with PBS buffer solution, and it is qualified to detect surplus fat rate.The gained precipitation is cell wall skeleton, claims to dilute with sterile distilled water by 50mg/ml after the weight in wet base, and rearmounted-20 ℃ of preservations of sterilization are stand-by.Fill lyophilizing operation: by following formulated semi-finished product (is example with preparation 5000ml semi-finished product).Nocardia rubra cytoskeleton 600mg, Dextran 40 150g, sterile water for injection 5000ml after semi-finished product prepare, make its mix homogeneously with magnetic stirring apparatus.Every bottle of 0.5ml of fill, lyophilizing after the fill.And through becoming inspection to make its every bottle to contain the nocardia rubra skeleton and be no less than 60 μ g, Dextran 40 15mg.Product of the present invention is storage life 2 years at normal temperatures.
Experimental example:
Product of the present invention carries out clinical experiment in the women and infants of Shenyang City hospital, and its result is as follows:
Materials and methods
One, research method: open multicenter randomized control study
(1) study subject alternative condition:
1. the age is at 23-45 between year, married non-anemia of pregnant woman woman.
2. cervix uteri has erosion, except canceration person.
3. the moon is no less than 25 days persons through the rule cycle.
4. can adhere to finishing person's course of treatment.
5. during being tried without the other treatment method.
(2) study subject exclusion condition:
1. colpocytology plate coating checking result is II
BAbove person.
2. cervix uteri has canceration person.
3. various vaginitiss or acute, subacute pelvic inflammatory disease person are arranged.
4. in 3 months puerperal.
5. many kinds of medicines have allergies person.
(3) study subject example number:
Be total up to 75 examples, be distributed in test group 50 examples by 2: 1 random tables, matched group 25 examples.
(4) medicine of Shi Yonging and method:
1. test group:
Medicine is Lyopgized Nocardia rubra-cell Wall Skeleton preparation (hereinafter to be referred as a promise card liniment), and specification is that every peace bottle includes cell wall skeleton (hereinafter to be referred as Nr-CWS) 60 μ g lyophilized powders, is the developed product of applicant unit, lot number 950321.
Using method: after removing cervix uteri surface secretions, behind 2.0ml physiological saline solution promise card liniment 60 μ g lyophilized powders, soak aseptic magnetic tape trailer rope cotton balls with medicine and place the cervical erosion place, take out voluntarily by the patient after 24 hours.Add medicine to totally 6 times weekly 2 times.
2. matched group:
Medicine is the Albothyl concentrated solution, and every gram contains Albothyl 360mg, is German BYK company product, lot number: J940475.
Using method: at first use 1: 5 diluent flushing cervix uteri, remove cervical mucus and intravaginal secretions with gauze piece, the Cotton Gossypii piece that will soak into concentrated solution then is close to the i.e. taking-up after three minutes of rotten to the corn place, and this moment, rotten to the corn face bleached entirely.Above-mentioned treatment is secondary weekly, totally 6 times.
The experimenter of test group and matched group is all in the 2-3 days begin treatments in the clean back of menstruation.
(5) cervical erosion diagnostic criteria
1. calibration
Slightly: rotten to the corn face is less than 1/3 of whole cervix uteri area.
Moderate: rotten to the corn face accounts for the 1/3-2/3 of whole cervix uteri area.
Severe: rotten to the corn face accounts for more than 2/3 of whole cervix uteri area.
2. typing: be divided into by rotten to the corn depth degree:
Simple type: rotten to the corn surface smoothing.
Granular pattern: rotten to the corn surface is papillae, injustice.
(6) observe item:
1. before the medication:
(1) conventional inquiry medical history is done gynecologial examination.
(2) vaginal secretions is checked cleannes, is divided into I, II, III degree, looks into the infusorian mycete.
(3) do the colpocytology plate coating checking, except canceration.
(4) range estimation cervical erosion area carries out calibration, typing by the diagnosis standard.
(5) have a blood test, routine urinalysis, liver function (GPT or ALT) renal function (BUN, Cr).
(6) arrange the special messenger to treat and observe, so that unified standard.
2. during the medication:
(1) the suggestion patient avoids sexual life during the treatment.
(2) whole body of inquiry medicine and the situation of partial untoward reaction.
(3) note observing pudendum, the partial untoward reaction of vagina before each medicine-feeding, leucorrhea changes (character and amount).Cervical erosion localized variation (scope and the degree of depth).
3. after the treatment
Menstruation next time was checked afterwards, continued the inquiry symptom, observed cervical erosion localized variation (comprising the area and the depth), and vaginal secretions amount and character change, and carry out efficacy determination.After the last medicine-feeding, the cytolgical examination of repetitive therapy provagina and experiment city check (blood, routine urinalysis, liver, renal function).
(7) curative effect determinate standard
Recovery from illness: rotten to the corn face hour, cervix uteri is smooth, transference cure.
Effectively: the rotten to the corn face reduced of upperlip 2mm shoals sx.
Invalid: subjective symptoms and sign do not have change.
Worsen: rotten to the corn face enlarges, deepens, sx.
(8) date processing and statistical method
Unified scheme, unified form, uniform data is handled.Statistical method is the X2 check.
The result
1. basic condition relatively: the outpatient service patients of cervical ruin is pressed random table 50 routine application promise card liniments treatments and is test group, and 25 example application Albothyls are treated and are matched group.Basic conditions such as the age of two groups of study subjects, age of menarche, pregnant time, parity see Table 1.
The age of table 1 study subject, age of menarche, pregnant time, the comparison of parity
| Age | Menophania | Pregnant time | Parity | ||||||
| The example number | Average | Standard deviation | Average | Standard deviation | Average | Standard deviation | Average | Standard deviation | |
| The experimental group matched group | 50 25 | 35.88 34.44 | 6.88 5.87 | 14.14 14.16 | 0.95 0.94 | 1.24 1.16 | 0.48 0.37 | 0.94 1.00 | 0.24 |
| The significance of two group differences | P＝0.3737 | P＝.09315 | P＝0.4349 | P＝0.2205 | |||||
At minimum 24 years old of the age between two groups, maximum 45 years old, two groups of study subject basic condition there was no significant differences had comparability (P＞0.005) as seen from the above table.
2. clinical manifestation
2.1 two groups of patient's cervical erosion calibration, typing situation see Table 2, table 3.
Table 2 liang group patient cervical erosion calibration, typing are relatively
| Before the medication | Check for the third time | ||||||
| Slightly | Moderate | Severe | Normally | Slightly | Moderate | Severe | |
| The test group matched group | 21 8 | 24 10 | 5 7 | 44 19 | 6 5 | 1 | |
Before the test group medication and the significance test of check for the third time (accurately probability) (P＜0.01.Matched group is with similar (P＜0.01 of test group.See table 11 for details, down together.
Test group slightly accounts for 42% as seen from the above table, moderate accounts for 48%, and severe accounts for 10%, and matched group slightly accounts for 32%, moderate accounts for 40%, severe accounts for 24%, and treatment back test group cervix uteri normally accounts for 88%, slightly accounts for 12%, the matched group cervix uteri normally accounts for 76%, slightly account for 20%, moderate accounts for 4%, is better than matched group from the percentage ratio test group curative effect that rotten to the corn degree occupied.
The contrast of table 3 cervical erosion typing
| Before the medication | Normally | Check for the third time | |||||
| Simple type | Granular pattern | The nipple type | Simple type | Granular pattern | The nipple type | ||
| The test group matched group | 30 10 | 17 11 | 3 4 | 44 19 | 2 2 | 3 2 | 1 2 |
Annotate: in cervical erosion calibration and typing two tables: " normally " one designs at inserting " 0 " in the curative effect.Test group medication significance test preceding and check for the third time (accurately probability) (P＜0.01), matched group similar to test group (P＜0.01).
Account for 60% by test group simple type before table 3 visible (1) treatment, granular pattern accounts for 34% nipple type and accounts for 6%.The matched group simple type accounts for 40%, and granular pattern accounts for 44%, and the nipple type accounts for 16%.Treatment back test group simple type accounts for 4%, and granular pattern accounts for 6%, and the nipple type accounts for 2%, and normal person is 88%.The matched group simple type accounts for 4%, and granular pattern accounts for 4%, and the nipple type accounts for 8%, normally accounts for 76%.The test group curative effect is better than matched group.
2.2 before and after the medication leucorrhea amount, leucorrhea character see Table 4, table 5
The contrast of table 4 leucorrhea amount
| Before the medication | Check for the first time | Check for the second time | Check for the third time | |||||||||
| Normally | Many slightly | A lot | Normally | Many slightly | A lot | Normally | Many slightly | A lot | Normally | Many slightly | A lot | |
| The test group matched group | 27 13 | 21 7 | 2 5 | 45 18 | 4 6 | 1 1 | 50 21 | 4 | 50 23 | 2 | ||
After the test group medication with the significance test (accurately probability) (P＜0.01) of check for the third time.Matched group similar to test group (P＜0.01).As seen from the above table: much more slightly leucorrhea is measured normal person and accounts for 54% in the preceding test group of (1) treatment, to account for 42%, much accounts for 4%.Much more slightly matched group normally accounts for 52%, to account for 28%, much accounts for 20%.(2) treatment back leucorrhea amount normally accounts for 100%, does not have many slightly or a lot.Much more slightly matched group normally accounts for 92%, to account for 8%.Test group or matched group leucorrhea amount before and after treatment has highly significant difference (P＜0.01), leucorrhea is measured shared percentage ratio and sees in two groups, (the normal person of recheck test group accounts for 100% for the second time to be better than matched group in the improvement of test group to the leucorrhea amount, for the first time check normal person and account for 90%, and the normal person of matched group is respectively 72%, 82%).
The contrast of table 5 leucorrhea character
| Before the medication | Check for the first time | Check for the second time | Check for the third time | |||||
| Normally | Purulence | Normally | Purulence | Normally | Purulence | Normally | Purulence | |
| The test group matched group | 44 18 | 6 7 | 48 23 | 2 2 | 49 25 | 1 | 49 25 | 1 |
Test group medication significance test preceding and check for the third time (accurately probability) (P＜0.01).Matched group similar to test group (P＜0.01).
See that by table 5 the preceding test group leucorrhea of (1) treatment normally accounts for 88%, purulence accounts for 12%, and the matched group leucorrhea normally accounts for 72%, and purulence accounts for 24%.Treatment back test group leucorrhea normally accounts for 98%, and purulence accounts for 2%, and the matched group leucorrhea normally accounts for 100%.This shows, all depositing significant difference (P＜0.01) in the improvement of leucorrhea character before and after the treatment for two groups.Test group is 98% improving on the leucorrhea character normal person, and matched group is 100%, both zero differences (P＞0.05).Leucorrhea amount and character often are patient main suit's symptom, estimate relevant therewith.
2.3 vagina cleanness degree, cervical smear, Ba surname ratings sees Table 6
Table 6 vagina cleanness degree, cervical smear, Ba surname ratings
| Vagina cleanness degree | Ba surname ratings | |||||||||||
| Before the medication | Check for the third time | Before the medication | Check for the third time | |||||||||
| The I degree | The II degree | The III degree | The I degree | The II degree | The III degree | The I degree | The II degree | The III degree | The I degree | The II degree | The III degree | |
| The test group matched group | 22 14 | 28 11 | 47 23 | 3 2 | 30 13 | 20 12 | 49 25 | 1 | ||||
Vagina cleanness degree and cervical smear Ba surname ratings between two groups by statistics, in treatment P value in previous existence all less than 0.01, the equal highly significant of difference.The safety and the practical value of prompting medicine.
3, efficacy evaluation sees Table 7
Table 7 efficacy evaluation
| Recovery from illness | Effectively | Invalid | |
| The test group matched group | 44 19 | 6 6 | 0 0 |
The test group cure rate accounts for 88% as seen from Table 7, and effective percentage accounts for 12%, total effective rate 100%, and the matched group cure rate accounts for 72%, and effective percentage accounts for 28%, and total effective rate is 100%, and is not remarkable through both differentiations of X2 statistical test.
4, safety and untoward reaction see Table 8
Table 8 untoward reaction
| Total example | Have | Do not have | |
| The test group matched group | 50 25 | 0 0 | 50 25 |
Test group 50 examples, matched group 25 examples, all side reaction appears in none example, and prompting promise card liniment is applied to clinical safety, reliability.
Before and after the treatment lab index check result see Table 9, table 10
Lab index check result before and after table 9 treatment
| The example number | Bb (g/L) means standard deviation | RBC (10/L) means standard deviation | WBC (10/L) means standard deviation | BUN (mg/D1) means standard deviation | Cr (mg/D1) means standard deviation | ||
| Test group | After treating before the treatment | 50 50 | 133.80±9.02 137.56±3.69 | 3.95±0.23 3.96±0.46 | 7.03±1.95 7.29±1.23 | 4.45±2.22 4.20±1.55 | 60.07±18.49 65.85±21.88 |
| The P value of difference before and after the treatment | P＝0.0014 | P＝0.0806 | P＝0.1104 | P＝0.5527 | P＝0.1013 | ||
| Matched group | After treating before the treatment | 25 25 | 137.76±3.49 138.52±4.45 | 4.00±0.15 4.03±0.13 | 6.80±1.38 7.20±1.24 | 4.25±1.26 3.88±1.37 | 74.82±23.80 68.23±24.48 |
| The P value of difference before and after the treatment | P＝0.1119 | P＝0.4301 | P＝0.3115 | P＝0.3791 | P＝0.3205 | ||
The significance test of every index difference before and after table 10 test group and the treatment of control group:
| Hb | RBC | WBC | BUN | Cr | |
| After treating before the treatment | P＝0.0704 P＝0.122 | P＝0.3963 P＝0.964 | P＝0.6048 P＝0.7019 | P＝0.8684 P＝0.5754 | P＝0.0071 P＝0.7377 |
The observation of every index before and after the medication
Survey erythrocyte before and after 75 routine experimenter's medications, erythrocyte is counted, leukocyte is counted, transaminase, the plain ammonia of hematuria, blood creatinine, change as shown in table 9ly, every index is compared in two groups, and majority parameters statistical discrepancy does not have significance (P＞0.05), though minority index difference has significance, its average is all in normal range.The result sees table 9, table 10 for details.The used medicine of presentation of results test group and matched group all is safe.
6. card side's significance of every index sees Table 11 before and after the medication
| Leukorrhagia | The cervical erosion calibration | The cervical erosion typing | The leucorrhea character | The guiding cleannes | Ba surname ratings | |
| Before the experimental group medication with the significance test of checking difference for the third time (accurately probabilistic method) | P＜0.05 | P＜0.01 | P＜0.01 | P＞0.05 | P＜0.01 | P＜0.01 |
| Before the matched group medication with the significance test of checking difference for the third time (accurately probabilistic method) | P＜0.05 | P＜0.01 | P＜0.01 | P＜0.01 | P＜0.01 | P＜0.01 |
| The significance test of difference before experimental group and the matched group medication (accurately probabilistic method) | P＞0.05 | P＞0.05 | P＞0.05 | P＞0.05 | P＞0.05 | P＞0.05 |
| Experimental group and matched group are checked the significance test (accurately probabilistic method) of difference for the third time | P＞0.05 | P＞0.05 | P＞0.05 | P＞0.05 | P＞0.05 | P＞0.05 |
From the result of this test, two kinds of medicines all have significant curative effect, and especially experimental group treatment cervical erosion has obtained gratifying curative effect especially, and cure rate reaches 88%, and total effective rate reaches 100%, and both all can make vaginal secretions reduce and character is improved.Two kinds of side effects of pharmaceutical drugs reactions are all very little, and the part is not had the obvious stimulation symptom, do not damage normal structure, and safety is good, and both are the medicine for external use of highly effective and safe treatment cervical erosion easy to use.Simultaneously administering mode is reasonable, and it is abundant that the magnetic tape trailer cotton balls is close to rotten to the corn face effect, and takes off more conveniently voluntarily, and the patient extremely takes like a shot.
Therefore, can think that promise card liniment is that the good medicine that has protective effect on cancer risk again is worthy to be popularized for the cervical erosion treatment provides new approach.
For the big granular pattern of area, nipple type cervical erosion, course of treatment is healing person fully, can consider to use 2-3 the course of treatment, to obtain better therapeutic effect.
Claims (9)
1. preparation that is used for the treatment of cervical erosion is characterized in that comprising the cell wall skeleton product of nocardia rubra.
2. preparation according to claim 1 is characterized in that said preparation also comprises its pharmaceutically acceptable excipient.
3. preparation according to claim 1 and 2, it is characterized in that described nocardia rubra on February 5th, 2002 in the common micro-organisms center preservation of Chinese microbial preservation administration committee, deposit number is: CGMCC No.0712.
4. preparation according to claim 2 is characterized in that described pharmaceutically acceptable excipient is a Dextran 40.
5. preparation according to claim 2 is characterized in that forming according to said preparation, is per 0.5 milliliter, and the content of the cell wall skeleton product of described nocardia rubra is 60 micrograms.
6. preparation according to claim 5 is characterized in that forming according to said preparation, is per 0.5 milliliter, contains 15 milligrams of the excipient of Dextran 40.
7. one kind prepares the method for the treatment of the cervical erosion preparation, comprising:
Nocardia rubra is increased bacterium cultivate, collect thalline, cell pulverization, process DNA enzyme, RNA enzyme, pronase, tryptic purification, get the Lyopgized Nocardia rubra-cell Wall Skeleton product after the grease removal;
The Lyopgized Nocardia rubra-cell Wall Skeleton product that obtains with pharmaceutically acceptable mixed with excipients, is obtained a preparation.
8. method according to claim 7 is characterized in that described pharmaceutically acceptable excipient is a dextran.
9. method according to claim 7, it is characterized in that described nocardia rubra be on February 5th, 2002 in the common micro-organisms center preservation of Chinese microbial preservation administration committee, deposit number is: the nocardia rubra of CGMCC No.0712.
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| CN1935262B (en) * | 2005-09-23 | 2010-12-29 | 沈阳胜宝康生物制药有限公司 | Use of red Nocardia cyto skeleton for preparing anti human papillomavirus medicine |
| CN108795859A (en) * | 2017-05-03 | 2018-11-13 | 辽宁格瑞仕特生物制药有限公司 | Purposes of the Lyopgized Nocardia rubra-cell Wall Skeleton as natural killer cells enhancer of proliferation |
| 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 |
| KR20210114436A (en) * | 2019-01-15 | 2021-09-23 | 랴오닝 그레이티스트 바이오-파마슈티컬 컴퍼니 리미티드 | Products derived from Rhodococcus louver and pharmaceutical uses thereof |
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| EP4056682A4 (en) * | 2020-01-21 | 2023-01-18 | Liaoning Greatest Bio-Pharmaceutical Co., Ltd. | Use of nocardia rubra cell wall skeleton in regenerative medicine |
| CN112063529A (en) * | 2020-08-13 | 2020-12-11 | 魏玲娟 | Red card skeleton powder and preparation method thereof |
| CN115089617A (en) * | 2022-08-03 | 2022-09-23 | 辽宁格瑞仕特生物制药有限公司 | Application of nocardia rubra cell wall skeleton in treatment of chronic cervicitis |
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2002
- 2002-03-08 CN CNB021092583A patent/CN1291725C/en not_active Expired - Lifetime
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