CN112999335A - Preparation method of anti-HPV slow-release hydrogel for preventing and treating various gynecological inflammations in female vagina - Google Patents
Preparation method of anti-HPV slow-release hydrogel for preventing and treating various gynecological inflammations in female vagina Download PDFInfo
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- CN112999335A CN112999335A CN202110216355.4A CN202110216355A CN112999335A CN 112999335 A CN112999335 A CN 112999335A CN 202110216355 A CN202110216355 A CN 202110216355A CN 112999335 A CN112999335 A CN 112999335A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The invention provides a preparation method of a sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in female vagina, which comprises the following steps: (1) weighing each component according to the proportion; (2) swelling the composite gel matrix; (3) mixing the plukenetia volubilis linneo oil and the cinnamic acid, and adding the swelling composite gel matrix to obtain a gel mixture; (4) dissolving propylene glycol sodium alginate to obtain a gel protective agent; (5) respectively adding the recombinant human interferon and the lactoferrin into the gel protective agent and the swelling composite gel matrix to obtain a drug mixture I and a drug mixture II; (6) mixing with the gel mixture to obtain a sustained-release hydrogel product; the invention realizes the effective combination of the recombinant human interferon, the lactoferrin and the plukenetia volubilis linneo oil, has better biological adhesion and strength, high stability of gel structure, obvious drug effect, safety and reliability, can effectively prevent and treat female vagina and cervicitis and resist HPV virus.
Description
Technical Field
The invention relates to the technical field of gynecological medicines, in particular to a preparation method of a sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in female vagina.
Background
Vaginitis and cervicitis are common gynecological diseases which are easy to occur in women of reproductive age and mainly caused by bacterial and viral infections, and common pathogens comprise: human Papilloma Virus (HPV), staphylococcus, escherichia coli, streptococcus, anaerobes, etc., with HPV predominating. High-risk Human Papilloma Virus (HPV) infection is the fundamental pathogenic factor of cervical cancer, most Cervical Intraepithelial Neoplasia (CIN) is accompanied by HPV infection, and according to epidemiological statistics, almost all cervical cancer cases are caused by HPV infection, so that the method has important significance for the prevention and control of HPV virus on female physiological health.
Vaginal administration is one of important administration routes for preventing and treating female reproductive system diseases, in the existing anti-HPV drugs, lotion, suppository, gel and the like are mainly taken as common dosage forms, and the traditional gel dosage forms often have the defects of uneven drug dispersion, low biological adhesion, short local action time and the like; moreover, for the slow-release gel preparation containing interferon, the effective ingredients of the medicine are single, the biological activity of the interferon is easily influenced in the preparation process, the stability is low, the curative effect of the medicine is greatly influenced, and the effects of preventing and treating female vagina inflammation and cervical inflammation and resisting HPV virus are not ideal. Therefore, a sustained-release hydrogel containing the recombinant human interferon, which has high biological adhesion, high stability and obvious drug effect, is found to be effectively applied to the prevention and treatment of various gynecological inflammations and HPV (human papilloma Virus) resistance.
Disclosure of Invention
In view of the above, the invention provides a preparation method of a sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in female vagina.
The technical scheme of the invention is realized as follows:
the invention provides a preparation method of a sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in female vagina, which is characterized by comprising the following steps: the method comprises the following steps:
step 1: respectively taking recombinant human interferon, lactoferrin, mei teng fruit oil, propylene glycol sodium alginate, cinnamic acid and a composite gel matrix for later use;
step 2: swelling the composite gel matrix in water for injection, which is 50-80 times the weight of the composite gel matrix, for 24-30 hours to obtain a swelling composite gel matrix;
and step 3: stirring and mixing the plukenetia volubilis linneo oil and cinnamic acid in a water bath at 35-40 ℃ for 5-10 min, adding the mixture into 60-70% of a swelling composite gel matrix, uniformly mixing, and adjusting the pH to 6.5-7.0 to obtain a gel mixture;
and 4, step 4: dissolving propylene glycol sodium alginate with 1-3 times of injection water by weight to obtain a gel protective agent;
and 5: respectively adding recombinant human interferon and lactoferrin into a gel protective agent and the balance of the swelling composite gel matrix, and stirring and mixing to obtain a drug mixture I and a drug mixture II;
step 6: and uniformly stirring the medicine mixture I, the medicine mixture II and the gel mixture to obtain the slow-release hydrogel product.
According to the invention, cinnamic acid is used as a plukenetia volubilis linneo oil carrier and is mixed with the composite gel matrix in a warm water bath, so that the mixing stability of the plukenetia volubilis linneo oil and the composite gel matrix is promoted, the distribution of the plukenetia volubilis linneo oil is promoted to be more uniform, and the stability and the biological adhesion of hydrogel are improved; on the other hand, the propylene glycol sodium alginate is used as a protective agent of the recombinant human interferon to ensure the biological activity of the recombinant human interferon in a gel mixture, and the uniform and stable mixing of a drug mixture I, a drug mixture II and the gel mixture is effectively realized by utilizing a composite gel preparation containing lactoferrin, so that the stability of the sustained-release hydrogel is improved, the sustained-release hydrogel has good biological adhesion and strength, is beneficial to the local stable and slow release of the drug, and is effectively applied to the prevention and treatment of various gynecological inflammations and HPV viruses.
Further explaining, in the step 1, the weight parts of the components are as follows: 0.15-0.35 part of recombinant human interferon, 0.1-0.2 part of lactoferrin, 0.4-0.6 part of maytenia fruit oil, 0.01-0.05 part of propylene glycol sodium alginate, 0.005-0.01 part of cinnamic acid and 120-160 parts of composite gel matrix.
Further, the composite gel matrix comprises chitosan, carrageenan and beta-sodium glycerophosphate, wherein the deacetylation degree of the chitosan, the carrageenan and the beta-sodium glycerophosphate are more than 90% in a mass ratio of 8:1: 0.3.
Further, the composite gel matrix is prepared by dissolving chitosan with a deacetylation degree of more than 90% and carrageenan in an acetic acid aqueous solution with a concentration of 0.1-0.15 mol/L according to a material-liquid ratio of 1.5-2 g/ml and 0.8-1.0 g/ml, mixing uniformly, adding beta-sodium glycerophosphate, and dropwise adding a sodium hydrogen phosphate solution to adjust the pH value to 6.8-6.9.
Further, in the step 3, triethanolamine is used as a pH regulator to regulate the pH of the gel mixture to 6.5-7.0.
Further explaining, in the step 5, lactoferrin is added to the swelling composite gel matrix under the continuous stirring state of 30-50 rpm to obtain a drug mixture II.
Further, step 2 comprises sterilizing the swollen composite gel matrix at 110 deg.C under 0.08MPa, and cooling to room temperature.
The slow release hydrogel is prepared by the preparation method of the slow release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in the female vagina.
Compared with the prior art, the invention has the beneficial effects that: the invention provides a preparation method of a sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV (human papilloma Virus) in female vagina, which utilizes a composite gel matrix, propylene glycol sodium alginate and cinnamic acid to realize effective combination of recombinant human interferon, lactoferrin and mei teng fruit oil, so that the obtained sustained-release hydrogel not only greatly improves the biological activity of the recombinant human interferon, but also combines the lactoferrin and the mei teng fruit oil, effectively achieves the effects of better preventing and treating female vagina and cervical inflammation and resisting HPV virus, improves the immune function of a patient and reduces the level of inflammatory factors; and the gel has better biological adhesion and strength, high stability of gel structure, obvious drug effect, safety and reliability, is favorable for prolonging local action time and improving the slow release effect of the drug.
Detailed Description
In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.
The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.
The materials, reagents and the like used in the examples of the present invention can be obtained commercially without specific description.
Example 1
The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in the female vagina comprises the following steps:
step 1: according to the weight portion ratio, 0.15 portion of recombinant human interferon, 0.1 portion of lactoferrin, 0.4 portion of mei teng fruit oil, 0.01 portion of propylene glycol sodium alginate, 0.005 portion of cinnamic acid and 120 portions of composite gel matrix are respectively taken for standby;
the composite gel matrix is prepared by dissolving chitosan with the deacetylation degree of more than 90% and carrageenan in 0.1mol/L acetic acid aqueous solution according to the material-liquid ratio of 1.5g/ml and 0.8g/ml, mixing uniformly, adding beta-sodium glycerophosphate, and dropwise adding a sodium hydrogen phosphate solution to adjust the pH value to 6.8; the mass ratio of chitosan with deacetylation degree more than 90 percent, carrageenan and beta-sodium glycerophosphate is 8:1: 0.3;
step 2: swelling the composite gel matrix in 50 times of injection water for 24 hours to obtain a swelling composite gel matrix; sterilizing the swelling composite gel matrix at 110 ℃ under 0.08MPa, and cooling to room temperature;
and step 3: stirring and mixing the plukenetia volubilis linneo oil and the cinnamic acid in a water bath at 35 ℃ for 5min, adding the mixture into 60-70% of a swelling composite gel matrix, uniformly mixing, and regulating the pH value to 6.5 by using triethanolamine to obtain a gel mixture;
and 4, step 4: dissolving propylene glycol sodium alginate with 1 time of injection water to obtain a gel protective agent;
and 5: respectively adding recombinant human interferon and lactoferrin into a gel protective agent and the balance of the swelling composite gel matrix, and stirring and mixing to obtain a drug mixture I and a drug mixture II;
step 6: and uniformly stirring the medicine mixture I, the medicine mixture II and the gel mixture to obtain the slow-release hydrogel product.
Example 2
The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in the female vagina comprises the following steps:
step 1: according to the weight portion ratio, 0.35 portion of recombinant human interferon, 0.2 portion of lactoferrin, 0.6 portion of mei teng fruit oil, 0.05 portion of propylene glycol sodium alginate, 0.01 portion of cinnamic acid and 160 portions of composite gel matrix are respectively taken for standby;
the composite gel matrix is prepared by dissolving chitosan with the deacetylation degree of more than 90% and carrageenan in an acetic acid aqueous solution with the concentration of 0.15mol/L according to the material-liquid ratio of 2g/ml and 1.0g/ml respectively, mixing uniformly, adding beta-sodium glycerophosphate, and dropwise adding a sodium hydrogen phosphate solution to adjust the pH value to 6.9; the mass ratio of chitosan with deacetylation degree more than 90 percent, carrageenan and beta-sodium glycerophosphate is 8:1: 0.3;
step 2: swelling the composite gel matrix in 80 times of water for injection for 30 hours to obtain a swelling composite gel matrix; sterilizing the swelling composite gel matrix at 110 ℃ under 0.08MPa, and cooling to room temperature;
and step 3: stirring and mixing the plukenetia volubilis linneo oil and the cinnamic acid in a water bath at 40 ℃ for 10min, adding the mixture into 60-70% of a swelling composite gel matrix, uniformly mixing, and regulating the pH value to 7.0 by using triethanolamine to obtain a gel mixture;
and 4, step 4: dissolving propylene glycol sodium alginate in 3 times of injection water to obtain a gel protective agent;
and 5: respectively adding recombinant human interferon and lactoferrin into a gel protective agent and the balance of the swelling composite gel matrix, and stirring and mixing to obtain a drug mixture I and a drug mixture II;
step 6: and uniformly stirring the medicine mixture I, the medicine mixture II and the gel mixture to obtain the slow-release hydrogel product.
Example 3
The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in the female vagina comprises the following steps:
step 1: according to the weight portion ratio, 0.2 portion of recombinant human interferon, 0.15 portion of lactoferrin, 0.5 portion of mei teng fruit oil, 0.03 portion of propylene glycol sodium alginate, 0.008 portion of cinnamic acid and 145 portions of composite gel matrix are respectively taken for standby;
the composite gel matrix is prepared by dissolving chitosan with the deacetylation degree of more than 90% and carrageenan in 0.12mol/L acetic acid aqueous solution according to the material-liquid ratio of 1.8g/ml and 0.9g/ml, mixing uniformly, adding beta-sodium glycerophosphate, and dropwise adding a sodium hydrogen phosphate solution to adjust the pH value to 6.85; the mass ratio of chitosan with deacetylation degree more than 90 percent, carrageenan and beta-sodium glycerophosphate is 8:1: 0.3;
step 2: swelling the composite gel matrix in 65 times of injection water for 28 hours to obtain a swelling composite gel matrix; sterilizing the swelling composite gel matrix at 110 ℃ under 0.08MPa, and cooling to room temperature;
and step 3: stirring and mixing the plukenetia volubilis linneo oil and cinnamic acid in a water bath at 38 ℃ for 8min, adding the mixture into 60-70% of a swelling composite gel matrix, uniformly mixing, and regulating the pH value to 6.8 by using triethanolamine to obtain a gel mixture;
and 4, step 4: dissolving propylene glycol sodium alginate with 2 times of injection water to obtain a gel protective agent;
and 5: adding the recombinant human interferon into a gel protective agent, and stirring and mixing to obtain a drug mixture I; adding lactoferrin into the swelling composite gel matrix with the balance mass under the condition of continuously stirring at 40rpm to obtain a drug mixture II;
step 6: and uniformly stirring the medicine mixture I, the medicine mixture II and the gel mixture to obtain the slow-release hydrogel product.
Example 4
The present embodiment differs from embodiment 3 in that: the weight portion ratio of each component is as follows: 0.3 part of recombinant human interferon, 0.12 part of lactoferrin, 0.4 part of plukenetia volubilis linneo oil, 0.03 part of propylene glycol sodium alginate, 0.008 part of cinnamic acid and 145 parts of composite gel matrix; the rest is the same as in example 3.
Comparative example 1
This comparative example differs from example 3 in that: in the step 3, only mixing the plukenetia volubilis linneo oil with 60-70% by mass of the swelling composite gel matrix at normal temperature to obtain a gel mixture; the rest is the same as in example 3.
Comparative example 2
This comparative example differs from example 3 in that: in the step 3-5, mixing the plukenetia volubilis linneo oil, the cinnamic acid, the propylene glycol sodium alginate, the recombinant human interferon and the lactoferrin at normal temperature, adding the mixture to the swelling composite gel matrix, and uniformly stirring to obtain the slow-release hydrogel product.
Comparative example 3
This comparative example differs from example 3 in that: the composite gel matrix was replaced with poloxamer, and the rest was the same as in example 3.
1. To determine the properties of the sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in the vagina of a female, the sustained-release hydrogel products prepared in the above examples and comparative examples were subjected to stability, bioadhesion and gel strength tests.
(1) And (3) centrifugal test: taking 5.0g of each of 3 batches of samples, placing the samples in a centrifuge tube, centrifuging the samples at 3000r/min for 60min, standing the samples, and observing whether the layering phenomenon exists.
(2) Heat resistance and low temperature resistance test: and respectively taking 3 batches of samples, respectively placing 5g of the samples in packaging bottles, respectively placing in a 55 ℃ thermostat for 6h and a 4 ℃ refrigerator for 24h, taking out, placing to room temperature, and observing whether layering occurs or not.
(3) Gel bioadhesive testing: taking two sections of fresh rabbit vaginal tissues with the area of S, respectively fixing one end of the fresh rabbit vaginal tissue on a balance and the other end of the fresh rabbit vaginal tissue with the mucosa facing outwards, keeping the fresh rabbit vaginal tissue at 37 ℃ for 20min, taking 0.15g of slow-release hydrogel sample, coating the slow-release hydrogel sample on the two sections of vaginal tissues, enabling the two sections of vaginal tissues to be tightly attached, and adding a weight to the other end of the balance until the weight is increased to the extent thatTwo sections of tissues are just separated, the weight of the weight is m, and the biological adhesion force is the stripping force f of a unit area which is 0.98m/s (dyne/cm)2) Each sample was repeated three times and averaged.
(4) Gel strength test: 20g of each sustained-release hydrogel sample is put into a 50ml cylinder, the cylinder is placed in a water tank at 37 ℃ to enable the sample to be gelled, a 100g weight is adopted to be placed on a pressure push rod, the other end of the push rod is connected with a disk which is tightly contacted with the inner wall of the cylinder, the disk is provided with 6 round holes with the diameter of 2mm, the time required for the disk to be pressed and reduced by 2cm is used for representing the strength of the gel, and the measurement results are as follows:
the determination results in the table show that the sustained-release hydrogel prepared in the embodiments 1 to 4 of the invention has high bioadhesion and strength, and the stability is obviously improved, while the comparative examples 1 to 3 compare with the embodiment 3, it can be known that the stability and the bioadhesion of the sustained-release hydrogel of the comparative example 1 are reduced, and the cinnamic acid is used as the maytenus fruit oil carrier, and is mixed with the composite gel matrix in a warm water bath, so that the stability of the mixture of the maytenus fruit oil carrier and the composite gel matrix is promoted, the distribution of the maytenus fruit oil is promoted to be more uniform, and the stability and the bioadhesion of the hydrogel are improved. The bioadhesion in the comparative examples 2 and 3 is obviously reduced, and the stability of the comparative example 2 is reduced, which shows that the bioadhesion and strength can be obviously improved by independently compounding the drug mixture I, the drug mixture II and the gel mixture by adopting the composite gel matrix, the propylene glycol sodium alginate and the cinnamic acid and then compounding and mixing the drug mixture I, the drug mixture II and the gel mixture, the stability of the gel structure is improved, the local stable and slow release of the drug is facilitated, and the preparation method is effectively applied to the prevention and treatment of various gynecological inflammations and HPV viruses.
In addition, the biological activity of the recombinant human interferon in the sustained-release hydrogel prepared in the embodiments 1 to 4 of the present invention can be 3.0 × 106～5.0×106IU, biological activity > 1.0 × 10 per 1mg recombinant human interferon6IU。
2. Safety test of drugs
The sustained-release hydrogel products prepared in the above examples and comparative examples are respectively subjected to a vaginal mucosa irritation test, a skin allergy test and a reproductive toxicity test, and the results show that after the tested drug of the New Zealand rabbit, the feeding and the activity are normal, the reaction is quick, and the vaginal mucosa is smooth, congestion-free and edema-free after the dissection is observed by naked eyes; after the test of the test medicament of albino guinea pigs, skin has no erythema and edema, the sensitization rate is 0 percent, and no skin allergy is seen; the experimental adult rat and the infant rat are administrated by a gastric lavage method, male has no influence on reproductive capacity and sperm state, and female rat is not influenced in pregnancy, parturition, lactation and newborn.
3. Clinical drug effect experiment
(1) Selecting 96 patients (excluding serious liver and kidney dysfunction and organic lesion patients, serious metabolic system disease patients, malignant tumor patients and nervous system disease patients) with high-risk HPV (human papillomavirus) detection as positive combined chronic cervicitis in clinic symptoms diagnosis of an outpatient service in obstetrics and gynecology department, wherein the average age is 23-50 years, and the patients are randomly divided into 48 cases of a control group and an observation group; the control group was: commercial recombinant human interferon alpha 2b gel; the observation groups were: the sustained-release hydrogel prepared in embodiment 3 of the invention;
(2) the treatment method comprises the following steps: the medicine is used for treating 3 days of menorrhagia, injected into deep vagina for 1 g/time and 3 times/d, and is adjusted for 2 times/d after 14 days of continuous treatment, and 1 treatment course is 30 days;
(3) the curative effect standard is as follows:
and (3) healing: the white epithelium of the acetic acid of the cervix is examined by a colposcope, the secretion disappears, and the cervix is smooth;
the method has the following advantages: the area of the acetic acid white epithelium of the cervix is obviously reduced and the thickness is thinned by the colposcopy;
and (4) invalidation: no obvious change is found in the area of the acetic acid white epithelium of the cervix under the examination of colposcopy.
Total effective rate (%) - (number of cured cases + number of effective cases)/total number of cases × 100%.
The results in the table show that the total effective rate of the observation group can reach 97.92 percent, which is obviously higher than the total effective rate (72.92 percent) of the control group, and the cure rate is also obviously improved to 87.50 percent, which has no side effect, therefore, the slow-release hydrogel prepared by the invention has good treatment effect on female vagina inflammation and cervical inflammation caused by HPV virus infection, is completely reliable, and can be used for preventing and treating various gynecological inflammations and HPV virus.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (8)
1. A preparation method of a sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in female vagina is characterized in that: the method comprises the following steps:
step 1: respectively taking recombinant human interferon, lactoferrin, mei teng fruit oil, propylene glycol sodium alginate, cinnamic acid and a composite gel matrix for later use;
step 2: swelling the composite gel matrix in water for injection, which is 50-80 times the weight of the composite gel matrix, for 24-30 hours to obtain a swelling composite gel matrix;
and step 3: stirring and mixing the plukenetia volubilis linneo oil and cinnamic acid in a water bath at 35-40 ℃ for 5-10 min, adding the mixture into 60-70% of a swelling composite gel matrix, uniformly mixing, and adjusting the pH to 6.5-7.0 to obtain a gel mixture;
and 4, step 4: dissolving propylene glycol sodium alginate with 1-3 times of injection water by weight to obtain a gel protective agent;
and 5: respectively adding recombinant human interferon and lactoferrin into a gel protective agent and the balance of the swelling composite gel matrix, and stirring and mixing to obtain a drug mixture I and a drug mixture II;
step 6: and uniformly stirring the medicine mixture I, the medicine mixture II and the gel mixture to obtain the slow-release hydrogel product.
2. The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations in female vagina and resisting HPV according to claim 1 is characterized in that: in the step 1, the weight parts of the components are as follows: 0.15-0.35 part of recombinant human interferon, 0.1-0.2 part of lactoferrin, 0.4-0.6 part of maytenia fruit oil, 0.01-0.05 part of propylene glycol sodium alginate, 0.005-0.01 part of cinnamic acid and 120-160 parts of composite gel matrix.
3. The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations in female vagina and resisting HPV according to claim 1 is characterized in that: the composite gel matrix comprises chitosan, carrageenan and beta-sodium glycerophosphate, wherein the deacetylation degree of the chitosan, the carrageenan and the beta-sodium glycerophosphate are more than 90% in a mass ratio of 8:1: 0.3.
4. The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations in female vagina and resisting HPV according to claim 3 is characterized in that: the composite gel matrix is prepared by dissolving chitosan with a deacetylation degree of more than 90% and carrageenan in an acetic acid aqueous solution with a concentration of 0.1-0.15 mol/L according to a material-liquid ratio of 1.5-2 g/ml and 0.8-1.0 g/ml respectively, mixing uniformly, adding beta-sodium glycerophosphate, and dropwise adding a sodium hydrogen phosphate solution to adjust the pH value to 6.8-6.9.
5. The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations in female vagina and resisting HPV according to claim 1 is characterized in that: and 3, regulating the pH value of the gel mixture to 6.5-7.0 by adopting triethanolamine as a pH regulator.
6. The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations in female vagina and resisting HPV according to claim 1 is characterized in that: and step 5, adding lactoferrin into the swelling composite gel matrix under the continuous stirring state of 30-50 rpm to obtain a drug mixture II.
7. The preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations in female vagina and resisting HPV according to claim 1 is characterized in that: and 2, sterilizing the swelling composite gel matrix at 110 ℃ under 0.08MPa, and cooling to room temperature.
8. The sustained-release hydrogel prepared by the preparation method of the sustained-release hydrogel for preventing and treating various gynecological inflammations and resisting HPV in the female vagina according to any one of claims 1 to 7.
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