CN111789945A - Compound external preparation for treating gynecological inflammation - Google Patents
Compound external preparation for treating gynecological inflammation Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/42—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum viral
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39575—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from other living beings excluding bacteria and viruses, e.g. protozoa, fungi, plants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/40—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum bacterial
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The invention discloses a compound external preparation for gynecological inflammation, which mainly comprises 2-8% (W/W) of compound yolk antibody and 0.5-2% (W/W) of chitosan. The composite yolk antibody comprises an antigen 1 and HPV recombinant protein, wherein the mass ratio of the antigen 1 to the HPV recombinant protein is (1-5): (1-5). The antigen 1 is a mixture of candida albicans extracted protein, staphylococcus aureus extracted protein, gonococcus extracted protein and gardnerella extracted protein, and the mass ratio of the candida albicans extracted protein to the staphylococcus aureus extracted protein to the gonococcus extracted protein to the gardnerella extracted protein is 1:1:1: 1. The traditional Chinese medicine composition can effectively treat gynecological inflammation diseases such as internal yin pruritus, cervical erosion, fishy smell, leukorrhagia and the like caused by vaginal infection, and simultaneously reduces the recurrence rate of gynecological inflammation.
Description
Technical Field
The invention relates to the field of biomedicine, in particular to a compound external preparation for treating gynecological inflammation.
Background
Bacterial Vaginosis (BV) is one of the most common vaginal infections in women. Vaginal and vulvar infections are often accompanied by human flora imbalance, and vaginal infections after human flora imbalance are often accompanied by massive proliferation of a large number of candida, staphylococcus, gonococcus and gardnerella. A small number of patients may also be infected with HPV viruses, and therefore, it is necessary to administer a combination of bacteria and viruses in an vulvar care formulation for prophylactic and therapeutic purposes.
Human papillomavirus infection is closely related to the occurrence of cervical cancer, and high-risk HPV persistent infection is the primary factor causing the cervical cancer. HPV is a minute DNA virus whose genome is functionally divided into 3 regions, an early gene region (E), a late gene region (L) and a non-coding region (NCR). The ER region encodes the eight early proteins E1-E8, which are primarily involved in replication, transcription, translation, and cellular transformation of the viral genome. The LR region is responsible for encoding the major capsid protein L1 and the minor capsid protein L2, which constitute the viral protein capsid and are involved in viral proliferation. Targeting HPV E6 and E7 antibodies, the goal being to improve cellular immunity by increasing recognition of viral and tumor antigens. Neutralizing antibodies targeting HPV L1 and L2 proteins can prevent infection and effectively block HPV infection.
In view of the above, the present invention is needed to provide a compound external preparation for treating gynecological inflammation.
Disclosure of Invention
The invention aims to provide a compound external preparation for treating gynecological inflammation, which can effectively treat gynecological inflammation diseases such as internal yin pruritus, cervical erosion, stinking odor, leukorrhagia and the like caused by vaginal infection and reduce the recurrence rate of the gynecological inflammation.
In order to achieve the above purpose, the invention provides the following technical scheme:
a compound external preparation for treating gynecological inflammation comprises 2-8% (W/W) of compound yolk antibody and 0.5-2% (W/W) of chitosan as main active ingredients.
In some of these embodiments, the chitosan is a pharmaceutical grade chitosan. The chitosan has strong antifungal property. Generally, antifungal activity is exhibited when the concentration of chitosan reaches 100. mu.g/mL, and is inversely proportional to the size of chitosan particles. The polymerization degree of chitosan has a great influence on the antifungal property of chitosan, and when the polymerization degree is reduced, the types of fungi which can be inhibited by chitosan are reduced, but the inhibition degree is enhanced. The chitosan has good inhibition effect on escherichia coli, pseudomonas fluorescens, staphylococcus aureus, bacillus subtilis and the like.
In some embodiments, the composite yolk antibody comprises antigen 1 and an HPV recombinant protein, and the mass ratio of the antigen 1 to the HPV recombinant protein is (1-5): (1-5).
In some of these embodiments, the antigen 1 is a mixture of candida albicans, staphylococcus aureus, gonococcus and gardnerella extract proteins in a mass ratio of 1:1:1: 1. The mass ratio of the candida albicans extract protein to the staphylococcus aureus extract protein to the gonococcus extract protein to the gardner bacteria extract protein is 1:1:1:1, so that the inhibition effects of the antigen 1 on candida, staphylococcus, gonococcus and gardner bacteria can be balanced.
In some embodiments, the HPV recombinant protein is a mixture of HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein, and the mass ratio of the HPV L1 protein, the HPV L2 protein, the HPV E6 protein and the HPV E7 protein is 1:1:1: 1. The HPV L1 protein, the HPV L2 protein, the HPV E6 protein and the HPV E7 protein are set to be 1:1:1 by mass, so that the activity of HPV recombinant protein is higher, and the inhibition effect on candida, staphylococcus, gonococcus and gardnerella is better after the HPV recombinant protein is compounded with the antigen 1.
In some of these embodiments, the HPV L1 protein is a yeast expression system and the HPV L2 protein, the HPV E6 protein, and the HPV E7 protein are an E.
In the invention, the HPV L1 protein is generally expressed by a eukaryotic expression system to have activity, the cheapest mode is to produce by a yeast system, and the protein produced by a baculovirus system and a mammalian expression system has a structure which is more similar to that of a natural protein, but is not used generally because of complex production process and high price. The HPV L2, HPV E6 and HPV E7 proteins are expressed in an escherichia coli expression system, have higher biological activity and are far lower in cost than yeast expression systems and other mammal expression systems. According to the invention, the HPV L1 protein of the yeast expression system, the HPVL2 protein, the HPV E6 protein and the HPV E7 protein of the escherichia coli expression system are mixed and compounded, so that the activity of the HPV recombinant protein can be exerted to the maximum extent, the cost is saved, and the effect of inhibiting bacterial infection in vagina by the composite yolk antibody formed by combining the HPV recombinant protein and the antigen 1 is better.
In some embodiments, the preparation method of the composite yolk antibody comprises the following steps: 1) culturing Candida albicans, Staphylococcus aureus, gonococcus, Gardner's bacillus, extracting active protein, mixing to obtain antigen 1; 2) extracting and purifying recombinant HPV protein, adding antigen 1, and mixing the mixture with the following components (1-10): (1-10) adding Freund's adjuvant, and homogenizing at high speed in a high-speed homogenizer at 25000-30000rpm to form water-in-oil emulsion to obtain composite antigen 2; 3) applying the composite antigen 2 obtained in the step 2) to an immunized laying hen, and taking the egg of the immunized laying hen to obtain a yolk; 4) and purifying the yolk antibody IgY in the yolk to obtain the compound yolk antibody.
The culture process of Candida albicans, Staphylococcus aureus, gonococcus and Gardner bacteria is simple, does not need imported culture equipment, and can be cultured only in a safety laboratory. The preparation of genetic engineering strains is not needed, so that the bacteria are directly cultured, and antigen components are extracted after inactivation for animal immunity, which is closer to the natural state of immune reaction, and the components are safer.
IgY is ubiquitous in birds, reptiles and amphibians and is functionally equivalent to mammalian IgG. Studies have shown that the genetic composition and biological function of IgY is similar to that of mammalian IgG and IgE. The application of the IgY antibody has the following advantages: the antibody IgY can be obtained by collecting the eggs laid by the immunized hens without collecting blood; a small amount of antigen is used for immunizing the poultry, so that a large amount of specific IgY with uniform quality can be obtained; due to the large distance between the germ lines, no cross-serological reaction between avian IgY and mammalian immunoglobulins can occur. Therefore, IgY has a wide application value. The invention takes HPV L1 protein, HPV L2 protein, HPV E6 protein, HPV E7 protein, Candida albicans extracted protein, staphylococcus aureus extracted protein, gonococcus extracted protein and Gardner bacteria extracted protein as antigens to act on an immune laying hen to obtain immune eggs, and the immune eggs are purified to obtain the high-purity yolk antibody IgY which has high-efficiency immune effect and can improve the immune effect of a human body on Candida, staphylococcus, gonococcus, Gardner bacteria and HPV.
In some embodiments, the application of the composite antigen 2 obtained in step 2) to an immunized laying hen in step 3) is specifically: selecting egg-laying hens with high immune response capacity, applying an immune activation method, and adopting the composite antigen 2 prepared in the step 2) to carry out injection immunization, wherein 7 days are separated after the first injection, then the second injection is carried out by the same dosage and method, the 3 rd injection is carried out by the same dosage and method after the second injection, and the high immune eggs are picked from the 18 th day after the first injection.
In some embodiments, the yolk antibody IgY in the yolk purified in step 4) is specifically: taking the yolk obtained in the step 3), adding 10 times of purified water to dilute and stir uniformly, adjusting the pH to 5.5-6.0 by using acetic acid, standing for 10-16 hours at 4-6 ℃, centrifuging at 10000-.
The invention also provides application of the compound external preparation for treating gynecological inflammation in gynecological inflammation, wherein the gynecological inflammation comprises internal yin pruritus, cervical erosion, stinking odor and increased leucorrhea caused by vaginal infection.
Compared with the prior art, the compound external preparation for treating gynecological inflammation provided by the invention has the following beneficial effects:
the invention takes HPV L1 protein, HPV L2 protein, HPV E6 protein, HPV E7 protein, Candida albicans extracted protein, staphylococcus aureus extracted protein, gonococcus extracted protein and Gardner bacteria extracted protein as antigens to act on an immunized laying hen to obtain an immunized egg which is purified to obtain the high-purity yolk antibody IgY, which has high-efficiency immunization effect and can improve the immunization effect of a human body on Candida, staphylococcus, gonococcus, Gardner bacteria and HPV. The gynecological inflammation compound external preparation prepared by compounding the compound egg yolk antibody and the chitosan can effectively treat gynecological inflammation diseases such as internal yin pruritus, cervical erosion, fishy smell, leukorrhagia and the like caused by vaginal infection, and simultaneously reduces the recurrence rate of gynecological inflammation.
The invention has safe components, no antibiotics and no drug resistance; can be directly externally applied to the infected part, and has good treatment effect.
Detailed Description
The present invention will be described in detail with reference to specific examples.
Example 1
A compound external preparation for treating gynecological inflammation comprises 8% (W/W) of compound yolk antibody and 0.5% (W/W) of chitosan as main active ingredients.
The composite yolk antibody comprises an antigen 1 and HPV recombinant protein, wherein the mass ratio of the antigen 1 to the HPV recombinant protein is 1: 5.
the antigen 1 is a mixture of candida albicans extracted protein, staphylococcus aureus extracted protein, gonococcus extracted protein and gardnerella extracted protein, and the mass ratio of the candida albicans extracted protein to the staphylococcus aureus extracted protein to the gonococcus extracted protein to the gardnerella extracted protein is 1:1:1: 1.
In some embodiments, the HPV recombinant protein is a mixture of HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein, and the mass ratio of the HPV L1 protein, the HPV L2 protein, the HPV E6 protein and the HPV E7 protein is 1:1:1: 1.
The preparation method of the composite yolk antibody comprises the following steps: 1) separating Candida, Staphylococcus, gonococcus, and Gardner bacteria from body of colpitis patient, and culturing by conventional method; establishing a seed bank, including establishing a seed bacteria bank, establishing a bacteria cryopreservation and recovery standard method and establishing a bacteria culture process flow, so as to ensure the production stability of each batch of antigen bacteria, collecting the bacteria after the antigen bacteria are fermented and cultured, performing high-pressure bacteria dissolving and crushing in a homogenizer, extracting bacterial protein after the bacteria are crushed, mixing to obtain the antigen 1, analyzing the protein after the protein is extracted, and releasing according to a central control standard of an intermediate;
2) obtaining HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein gene sequences by a reverse transcription method, carrying out codon optimization on the gene sequences, expressing the HPV L1 protein in a yeast expression system by a genetic engineering method, expressing the HPV L2 protein, the HPV E6 protein and the HPV E7 protein in an escherichia coli expression system, establishing an engineering bacteria seed bank, establishing an effective protein expression and production process flow by production quality control, producing high-activity HPV recombinant protein after purifying, removing viruses and sterilizing the recombinant protein, mixing the HPV recombinant protein with the antigen 1 prepared in the step 1), adding Fowler's adjuvant into the mixed solution in a ratio of 1:10, placing the mixed solution into a high-speed homogenizer at 25000rpm to form a water-in-oil emulsion, and preparing a composite homogenized antigen 2; 3) selecting egg-laying hens with high immune response capacity, applying an immune activation method, and adopting the composite antigen 2 prepared in the step 2) to carry out injection immunization, wherein 7 days are separated after the first injection, the injection is carried out for the second time by the same dosage and method, the injection is carried out for the 3 rd time by 7 days separated after the second injection, and high immune eggs are picked from the 18 th day after the first injection; 4) adding 10 times of purified water into the yolk obtained in the step 3), diluting and stirring uniformly, adjusting the pH value to 6.0 by using acetic acid, standing for 16 hours at 4 ℃, centrifuging at a high speed of 12000r/min for 20 minutes, taking supernatant, ultrafiltering and concentrating the supernatant by 10 times, adding saturated ammonium sulfate, separating out IgY, centrifuging again to obtain high-purity protein precipitate, performing hydrophobic chromatography after protein re-melting to obtain a high-purity protein sample, filtering the protein sample by virus, ultrafiltering to change liquid, sterilizing and filtering to obtain a pure protein product, namely the composite yolk antibody.
Example 2
A compound external preparation for treating gynecological inflammation comprises 2% (W/W) of compound yolk antibody and 2% (W/W) of chitosan as main active ingredients.
The composite yolk antibody comprises an antigen 1 and HPV recombinant protein, wherein the mass ratio of the antigen 1 to the HPV recombinant protein is 5: 1.
the antigen 1 is a mixture of candida albicans extracted protein, staphylococcus aureus extracted protein, gonococcus extracted protein and gardnerella extracted protein, and the mass ratio of the candida albicans extracted protein to the staphylococcus aureus extracted protein to the gonococcus extracted protein to the gardnerella extracted protein is 1:1:1: 1.
In some embodiments, the HPV recombinant protein is a mixture of HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein, and the mass ratio of the HPV L1 protein, the HPV L2 protein, the HPV E6 protein and the HPV E7 protein is 1:1:1: 1.
The preparation method of the composite yolk antibody comprises the following steps: 1) separating Candida, Staphylococcus, gonococcus, and Gardner bacteria from body of colpitis patient, and culturing by conventional method; establishing a seed bank, including establishing a seed bacteria bank, establishing a bacteria cryopreservation and recovery standard method and establishing a bacteria culture process flow, so as to ensure the production stability of each batch of antigen bacteria, collecting the bacteria after the antigen bacteria are fermented and cultured, performing high-pressure bacteria dissolving and crushing in a homogenizer, extracting bacterial protein after the bacteria are crushed, mixing to obtain the antigen 1, analyzing the protein after the protein is extracted, and releasing according to a central control standard of an intermediate;
2) obtaining HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein gene sequences by a reverse transcription method, carrying out codon optimization on the gene sequences, expressing the HPV L1 protein in a yeast expression system by a genetic engineering method, expressing the HPV L2 protein, the HPV E6 protein and the HPV E7 protein in an escherichia coli expression system, establishing an engineering bacteria seed bank, establishing an effective protein expression and production process flow by production quality control, producing high-activity HPV recombinant protein after purifying, removing viruses and sterilizing the recombinant protein, mixing the HPV recombinant protein with the antigen 1 prepared in the step 1), adding Fowler's adjuvant into the mixed solution in a ratio of 10:1, placing the mixed solution into a high-speed homogenizer at a high speed of 30000rpm to form a water-in-oil emulsion, and preparing a composite homogenized antigen 2; 3) selecting egg-laying hens with high immune response capacity, applying an immune activation method, and adopting the composite antigen 2 prepared in the step 2) to carry out injection immunization, wherein 7 days are separated after the first injection, the injection is carried out for the second time by the same dosage and method, the injection is carried out for the 3 rd time by 7 days separated after the second injection, and high immune eggs are picked from the 18 th day after the first injection; 4) taking the yolk obtained in the step 3), adding 10 times of purified water to dilute and stir uniformly, adjusting the pH to 5.5 by using acetic acid, standing for 10 hours at 6 ℃, centrifuging at a high speed of 10000r/min for 30 minutes, taking supernatant, ultrafiltering and concentrating the supernatant by 5 times, adding saturated ammonium sulfate, separating out IgY, centrifuging again to obtain high-purity protein precipitate, performing hydrophobic chromatography after protein re-melting to obtain a high-purity protein sample, performing virus filtration on the protein sample, ultrafiltering to change liquid, sterilizing and filtering to obtain pure protein, namely the composite yolk antibody.
Example 3
A compound external preparation for treating gynecological inflammation comprises 5% (W/W) of compound yolk antibody and 1.2% (W/W) of chitosan as main active ingredients.
The composite yolk antibody comprises an antigen 1 and HPV recombinant protein, wherein the mass ratio of the antigen 1 to the HPV recombinant protein is 3: 2.
the antigen 1 is a mixture of candida albicans extracted protein, staphylococcus aureus extracted protein, gonococcus extracted protein and gardnerella extracted protein, and the mass ratio of the candida albicans extracted protein to the staphylococcus aureus extracted protein to the gonococcus extracted protein to the gardnerella extracted protein is 1:1:1: 1.
In some embodiments, the HPV recombinant protein is a mixture of HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein, and the mass ratio of the HPV L1 protein, the HPV L2 protein, the HPV E6 protein and the HPV E7 protein is 1:1:1: 1.
The preparation method of the composite yolk antibody comprises the following steps: 1) separating Candida, Staphylococcus, gonococcus, and Gardner bacteria from body of colpitis patient, and culturing by conventional method; establishing a seed bank, including establishing a seed bacteria bank, establishing a bacteria cryopreservation and recovery standard method and establishing a bacteria culture process flow, so as to ensure the production stability of each batch of antigen bacteria, collecting the bacteria after the antigen bacteria are fermented and cultured, performing high-pressure bacteria dissolving and crushing in a homogenizer, extracting bacterial protein after the bacteria are crushed, mixing to obtain the antigen 1, analyzing the protein after the protein is extracted, and releasing according to a central control standard of an intermediate;
2) obtaining HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein gene sequences by a reverse transcription method, carrying out codon optimization on the gene sequences, expressing the HPV L1 protein in a yeast expression system by a genetic engineering method, expressing the HPV L2 protein, the HPV E6 protein and the HPV E7 protein in an escherichia coli expression system, establishing an engineering bacteria seed bank, establishing an effective protein expression and production process flow by production quality control, producing high-activity HPV recombinant protein after purifying, removing viruses and sterilizing the recombinant protein, mixing the HPV recombinant protein with the antigen 1 prepared in the step 1), adding Fowler's adjuvant into the mixed solution in a ratio of 5:7, placing the mixed solution into a high-speed homogenizer at a high speed of 28000rpm to form a water-in-oil emulsion, and preparing a composite homogenized antigen 2; 3) selecting egg-laying hens with high immune response capacity, applying an immune activation method, and adopting the composite antigen 2 prepared in the step 2) to carry out injection immunization, wherein 7 days are separated after the first injection, the injection is carried out for the second time by the same dosage and method, the injection is carried out for the 3 rd time by 7 days separated after the second injection, and high immune eggs are picked from the 18 th day after the first injection; 4) adding 10 times of purified water into the yolk obtained in the step 3), diluting and stirring uniformly, adjusting the pH value to 5.7 by using acetic acid, standing for 13 hours at the temperature of 5 ℃, centrifuging at the high speed of 11000r/min for 25 minutes, taking supernatant, ultrafiltering and concentrating the supernatant by 8 times, adding saturated ammonium sulfate, separating out IgY, centrifuging again to obtain high-purity protein precipitate, performing hydrophobic chromatography after protein re-melting to obtain a high-purity protein sample, filtering the protein sample by virus, ultrafiltering to change liquid, sterilizing and filtering to obtain a pure protein, namely the composite yolk antibody.
Comparative example 1
The difference from example 3 is that the amount of chitosan added in comparative example 1 was 0.4 (W/W).
Comparative example 2
The difference from example 3 is that the amount of chitosan added in comparative example 2 was 2.1 (W/W).
Comparative example 3
The difference from example 3 is that the yolk antibody IgY of the preparation method of the composite yolk antibody of comparative example 3 was not purified.
Comparative example 4
The difference from example 3 is that the mass ratio of the candida albicans extract protein, the staphylococcus aureus extract protein, the gonococcus extract protein and the gardnerella extract protein in comparative example 4 is 1:2:3: 1.
Comparative example 5
The difference from example 3 is that the mass ratio of HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein in comparative example 5 is 3:1:2: 5.
Bacteriostasis test
The compound external preparation for gynecological inflammation prepared in the examples 1 to 3 and the comparative examples 1 to 5 is used for bacteriostasis experiments, the using concentration is 20%, and the experimental method comprises the following steps: the tube-disc method and the paper method are adopted simultaneously. Respectively densely streaking four bacteria of candida, staphylococcus, gonococcus and gardnerella to corresponding plate culture media, then placing two sterile steel oxford cups on each culture plate, respectively adding 0.2ml of 20% suspension in the oxford cups in the embodiments 1-3 and the comparative examples 1-5, simultaneously soaking the liquid medicine with the same concentration on the plate by using a paper sheet (the diameter is 6mm for standby after high-pressure sterilization), and adhering the liquid medicine to the plate, and culturing the bacteria at 37 ℃ for 24-48 hours to observe results; the fungi were incubated at 25 ℃ for one week and the results were observed.
The bacteriostatic diameter (mm) of the drugs around the oxford cup and the paper sheet was measured, and the results are shown in table 1:
TABLE 1
As shown in Table 1, examples 1 to 3 are all comparative examples 1 to 5.
Typical cases are:
thanks to certain woman, 26 years old, a staff member of a company in certain city of Guangdong province, the most obvious feeling of the lower body is itching and peculiar itching a few years ago, more importantly, sexual life is troubled for her, the woman feels dry and painful, and the woman has slight bleeding, and is diagnosed as mycotic vaginitis by a hospital. The external preparation of the invention in example 1 is changed to be used in 2019, 2 times a day, 28 days are taken as a treatment course, 7 days are separated, the second treatment course is used, the condition of the patient is obviously improved after the external preparation is used, the mould is checked to be negative, and other test results are all normal.
In the case of Li Shi, female, 30 years old, office clerk of a company in Guangdong province, private parts of the vagina were itchy, and the vagina fell and was hot before one year. Initially, it was not of great concern, and after one month, the symptoms worsened, the pain worsened, and increased white bands, grayish white with off-flavor appeared. This seriously affects her work and life. Bacterial vaginitis diagnosed by hospitals is slightly improved after treatment, and the symptoms are relieved but not completely disappeared. The condition reappears after a period of time and is more severe than before. The external preparation of the invention in the example 2 is changed to be used 2 times a day in 2020, and 28 days are a treatment course, so that the symptoms completely disappear and no secondary attack occurs.
Some company staff in Zhang, female, 25 years old, Guangdong province, started to appear more leucorrhea and fishy smell before the year, meanwhile, a lot of color spots appeared on the face, the whole person is old and old, and irregular bleeding also appears in the vagina. The hospital diagnoses the severe cervical erosion, and the hospital treatment is not improved. The external preparation of the invention in the embodiment 3 is changed to be used 2 times a day in 2020, 28 days are taken as a treatment course and are separated by 7 days, and then the second treatment course is used. After treatment, the disease condition is obviously improved, the leucorrhea is normal, and the color spots on the face are light.
The features of the embodiments and embodiments described above may be combined with each other without conflict.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (10)
1. The compound external preparation for gynecological inflammation is characterized in that the main active ingredients of the compound external preparation are 2-8% (W/W) of compound egg yolk antibody and 0.5-2% (W/W) of chitosan.
2. The compound external preparation for gynecological inflammation according to claim 1, wherein the chitosan is pharmaceutical grade chitosan.
3. The compound external preparation for gynecological inflammation according to claim 1, wherein the compound egg yolk antibody comprises antigen 1 and HPV recombinant protein, and the mass ratio of the antigen 1 to the HPV recombinant protein is (1-5): (1-5).
4. The compound external preparation for gynecological inflammation according to claim 3, wherein the antigen 1 is a mixture of Candida albicans extract protein, Staphylococcus aureus extract protein, gonococcus extract protein and Gardner bacteria extract protein, and the mass ratio of the Candida albicans extract protein, the Staphylococcus aureus extract protein, the gonococcus extract protein and the Gardner bacteria extract protein is 1:1:1: 1.
5. The compound external preparation for gynecological inflammation according to claim 4, wherein the HPV recombinant protein is a mixture of HPV L1 protein, HPV L2 protein, HPV E6 protein and HPV E7 protein, and the mass ratio of the HPV L1 protein, the HPV L2 protein, the HPV E6 protein and the HPV E7 protein is 1:1:1: 1.
6. The complex external preparation for gynecological inflammation according to claim 5, wherein the HPV L1 protein is a yeast expression system, and the HPV L2 protein, HPV E6 protein and HPV E7 protein are Escherichia coli expression systems.
7. The compound preparation for external use according to claim 6, wherein the preparation method of the compound egg yolk antibody comprises the following steps: 1) culturing Candida albicans, Staphylococcus aureus, gonococcus, Gardner's bacillus, extracting active protein, mixing to obtain antigen 1; 2) extracting and purifying recombinant HPV protein, adding antigen 1, and mixing the mixture with the following components (1-10): (1-10) adding Freund's adjuvant, and homogenizing at high speed in a high-speed homogenizer at 25000-30000rpm to form water-in-oil emulsion to obtain composite antigen 2; 3) applying the composite antigen 2 obtained in the step 2) to an immunized laying hen, and taking the egg of the immunized laying hen to obtain a yolk; 4) and purifying the yolk antibody IgY in the yolk to obtain the compound yolk antibody.
8. The compound external preparation for gynecological inflammation according to claim 7, wherein the application of the compound antigen 2 obtained in step 2) to an immunized laying hen in step 3) is specifically: selecting egg-laying hens with high immune response capacity, applying an immune activation method, and adopting the composite antigen 2 prepared in the step 2) to carry out injection immunization, wherein 7 days are separated after the first injection, then the second injection is carried out by the same dosage and method, the 3 rd injection is carried out by the same dosage and method after the second injection, and the high immune eggs are picked from the 18 th day after the first injection.
9. The external preparation of claim 7, wherein the yolk antibody IgY purified from the yolk in step 4) is selected from the group consisting of: taking the yolk obtained in the step 3), adding 10 times of purified water to dilute and stir uniformly, adjusting the pH to 5.5-6.0 by using acetic acid, standing for 10-16 hours at 4-6 ℃, centrifuging at 10000-.
10. The composite external preparation for gynecological inflammation according to any one of claims 1 to 9, for use in gynecological inflammation including pruritus vulvae, cervical erosion, bad smell of fish and increased leucorrhea due to vaginal infection.
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