CN107596350B - Recombinant human interferon expandable vaginal suppository and preparation method thereof - Google Patents
Recombinant human interferon expandable vaginal suppository and preparation method thereof Download PDFInfo
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- Medicinal Preparation (AREA)
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Abstract
The invention provides a recombinant human interferon expandable vaginal suppository and a preparation method thereof, wherein the expandable vaginal suppository comprises the following components in parts by weight: 0.1-1.0 part of recombinant human interferon, 10-50 parts of high molecular polymer, 50-200 parts of matrix and 500 parts of swelling carrier. The outer layer of the vaginal expansion suppository is coated with the high molecular polymer, so that the release speed and the release time of the recombinant human interferon are effectively controlled, and the drug effect duration of the vaginal expansion suppository can reach 24 hours at most; in addition, the invention improves the curative effect of the recombinant human interferon by 3-4 times under the coordination of the schisandra extract, the human placenta extract, the wild lily extract and the scutellaria extract.
Description
Technical Field
The invention belongs to the field of pessaries, relates to a vaginal expansion suppository and a preparation method thereof, and particularly relates to a recombinant human interferon vaginal expansion suppository and a preparation method thereof.
Background
The recombinant human interferon is a multifunctional high-activity induced protein obtained by fermenting, separating and highly purifying escherichia coli containing a high-efficiency expression human interferon gene, has obvious broad-spectrum antiviral effect and immunoregulation function, and has obvious curative effect and small side effect on Human Papilloma Virus (HPV) infected diseases such as cervical erosion, condyloma acuminatum, cervical carcinoma and the like. At present, the dosage forms of the recombinant human interferon are mainly tablets and suppositories, but the recombinant human interferon is unstable, the development difficulty of a new dosage form is higher, and the wide application of the recombinant human interferon is seriously influenced.
The tablet recombinant human interferon has the defects of difficult dissolution, weak effect, poor adaptability to the vagina and potential harm to the body of a patient; the suppository recombinant human interferon has the defects of slow disintegration speed, poor absorption effect, inconvenience in use, clothes pollution and the like, the drug effect is influenced by the body position of a patient, and affected parts such as fornix, ventral side and the like at the back of a vagina are difficult to contact with the drug.
CN 103751098B discloses a recombinant human interferon α a vaginal expansion suppository as well as a preparation method and a detection method thereof, and a protective agent of recombinant human interferon α a is added into the vaginal expansion suppository, so that the stability of the recombinant human interferon α a is improved, and the bioavailability of a medicine is improved.
CN 105012938A discloses a recombinant human interferon α b vaginal expansion suppository and a preparation method and a detection method thereof, the expansion suppository is added with a mixture of corydalis bungeana extractive, kaempferol-3-O- β -D sophoricoside and lauryl sodium sulfate, and magnetic microspheres formed by crosslinking esterified cassava modified starch and a crosslinking product of chitin-methyl cellulose through magnetic iron, and the mixture and the recombinant human interferon α b are synergistically enhanced, however, the recombinant human interferon α b and synergistic components thereof are mixed and distributed in a matrix to form a drug-containing matrix, the contact area of active components with a human body is reduced, the active components cannot be fully absorbed by the human body, waste is caused to a certain degree, and the optimal treatment effect of the suppository cannot be exerted.
Therefore, the recombinant human interferon expandable vaginal suppository and the preparation method thereof are provided, so that the expandable suppository not only has obvious treatment effect on HPV infection diseases, but also has lasting curative effect and small toxic and side effect, and has important significance in the field of vaginal suppositories.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides the recombinant human interferon expandable vaginal suppository and the preparation method thereof, the expandable vaginal suppository uses the recombinant human interferon as a main active ingredient, and a high molecular polymer is coated outside the expandable vaginal suppository, so that the expandable vaginal suppository has the advantages of remarkable curative effect and small toxic and side effects.
In a first aspect, the invention provides a vaginal expansion suppository, which comprises the following components in parts by weight: 0.1-1.0 part of recombinant human interferon, 10-50 parts of high molecular polymer, 50-200 parts of matrix and 500 parts of swelling carrier.
The vaginal dilation suppository provided by the invention adopts the recombinant human interferon as a main active ingredient, and the outer layer of the vaginal dilation suppository is coated with the high molecular polymer, so that the release speed and the action time of the active ingredient are controlled, the daily administration frequency is reduced, the recombinant human interferon can be better absorbed, distributed and metabolized by a human body, and the remarkable curative effect is fully exerted.
According to the present invention, the recombinant human interferon is 0.1 to 1.0 part by weight, for example, 0.1 part, 0.15 part, 0.2 part, 0.25 part, 0.3 part, 0.35 part, 0.4 part, 0.45 part, 0.5 part, 0.55 part, 0.6 part, 0.65 part, 0.7 part, 0.75 part, 0.8 part, 0.85 part, 0.9 part, 0.95 part or 1.0 part, preferably 0.05 to 0.5 part, and more preferably 0.1 part.
According to the present invention, the weight portion of the high molecular polymer is 10 to 50 parts, for example, 10 parts, 12 parts, 15 parts, 18 parts, 20 parts, 22 parts, 25 parts, 28 parts, 30 parts, 32 parts, 35 parts, 38 parts, 40 parts, 42 parts, 45 parts, 48 parts or 50 parts, preferably 30 to 50 parts, and more preferably 35 parts.
According to the present invention, the weight part of the matrix is 50 to 200 parts, for example, 50 parts, 60 parts, 70 parts, 80 parts, 90 parts, 100 parts, 110 parts, 120 parts, 130 parts, 140 parts, 150 parts, 160 parts, 170 parts, 180 parts, 190 parts or 200 parts, preferably 80 to 150 parts, and more preferably 120 parts.
According to the present invention, the weight portion of the swelling carrier is 500 portions, such as 100 portions, 120 portions, 150 portions, 180 portions, 200 portions, 220 portions, 250 portions, 280 portions, 300 portions, 320 portions, 350 portions, 380 portions, 400 portions, 420 portions, 450 portions, 480 portions or 500 portions, preferably 150 portions, 400 portions, and more preferably 300 portions.
According to the invention, the vaginal dilation suppository further comprises a traditional Chinese medicine composition.
The traditional Chinese medicine extract and the recombinant human interferon have obvious synergistic effect on the aspect of treating HPV, and after the traditional Chinese medicine composition is added, the treatment effect of the recombinant human interferon on female vaginal inflammation is enhanced by 3-4 times, so that the dosage of the interferon can be reduced under the same treatment effect, and the treatment cost and the side effect of the interferon are reduced.
According to the invention, the traditional Chinese medicine composition comprises the following components in parts by weight: 5-10 parts of schisandra extract, 8-20 parts of placenta hominis extract, 1-10 parts of wild lily extract and 1-10 parts of scutellaria extract.
According to the invention, the weight portion of the schisandra extract is 5-10, such as 5, 6, 7, 8, 9 or 10, preferably 6-8, and more preferably 8.
According to the present invention, the weight portion of the human placenta extract is 8 to 20 parts, such as 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, preferably 10 to 16 parts, and more preferably 15 parts.
According to the present invention, the weight portion of the lilium brownii extract is 1 to 10 parts, for example, 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, preferably 3 to 8 parts, and more preferably 6 parts.
According to the present invention, the weight portion of the scutellaria baicalensis extract is 1 to 10 parts, for example, 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, preferably 3 to 8 parts, and more preferably 6 parts.
According to the invention, the vaginal expansion suppository comprises the following components in parts by weight: 0.2-0.8 part of recombinant human interferon, 6-8 parts of schisandra extract, 10-16 parts of placenta hominis extract, 3-8 parts of wild lily extract, 3-8 parts of scutellaria extract, 30-50 parts of high molecular polymer, 80-150 parts of matrix and 400 parts of expansion carrier 150-.
According to the invention, the vaginal expansion suppository comprises the following components in parts by weight: 0.5 part of recombinant human interferon, 8 parts of schisandra extract, 15 parts of human placenta extract, 6 parts of wild lily extract, 6 parts of scutellaria extract, 35 parts of high molecular polymer, 120 parts of matrix and 300 parts of swelling carrier.
According to the present invention, the high molecular polymer includes any one or a combination of at least two of polylactic acid, polycaprolactone, a polylactic acid-glycolic acid copolymer or polyurethane, for example, a combination of polylactic acid and polycaprolactone, a combination of polylactic acid and polylactic acid-glycolic acid copolymer, a combination of polylactic acid and polyurethane, a combination of polycaprolactone and polylactic acid-glycolic acid copolymer, a combination of polycaprolactone and polyurethane, or a combination of polylactic acid-glycolic acid copolymer and polyurethane, preferably a polylactic acid-glycolic acid copolymer.
According to the invention, the matrix comprises any one or a combination of at least two of synthetic fatty acid ester, natural fatty acid ester, hydrogenated oil, lipid matrix or colloidal compound, and can be, for example, a combination of synthetic fatty acid ester and natural fatty acid ester, a combination of synthetic fatty acid ester and lipid matrix, a combination of synthetic fatty acid ester and colloidal compound, a combination of natural fatty acid ester and lipid matrix, a combination of natural fatty acid ester and hydrogenated oil, a combination of hydrogenated oil and lipid matrix, a combination of natural fatty acid ester and colloidal compound, or a combination of lipid matrix and colloidal compound, preferably a combination of synthetic fatty acid ester, hydrogenated oil and colloidal compound.
According to the invention, the weight ratio of the synthetic fatty acid ester to the colloidal compound is (1-10): 7-15):1, and may be, for example, 1:7:1, 2:8:1, 3:9:1, 4:10:1, 5:12:1, 6:13:1, 7:14:1, 8:12:1, 9:14:1 or 10:15:1, preferably (2-6): 10-12):1, and more preferably 5:12: 1.
According to the invention, the swelling carrier comprises any one or a combination of at least two of the tampon, the non-woven fabric or the elastic fiber, and can be, for example, a combination of the tampon and the non-woven fabric, a combination of the tampon and the elastic fiber, a combination of the non-woven fabric and the elastic fiber, or a combination of the tampon, the non-woven fabric and the elastic fiber, and further preferably a combination of chinlon, viscose fiber and acrylon.
According to the invention, the mass ratio of the chinlon, the viscose fiber and the acrylic fiber is (4-7): (1-3): (3-5), and can be 4:1:3, 5:2:4, 6:3:4, 6:2:5, 7:1:3, 7:2:5 and 7:3:5, for example.
According to the invention, the surface of the expansion suppository carrier is coated with a drug-containing matrix formed by lactobacillus, bifidobacterium and the matrix.
In the vaginal expansive suppository, the lactic acid bacteria and the bifidobacteria are used as active ingredients, so that various floras in the vagina can be balanced, the vaginal expansive suppository has a broad spectrum for treating vaginitis, and the vaginitis diseases can be fundamentally prevented and treated.
According to the invention, the weight portion of the lactobacillus in the vaginal expansion suppository is 10-30 parts, such as 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts or 30 parts.
According to the invention, the weight ratio of lactobacillus acidophilus, lactobacillus fermentum and lactobacillus bulgaricus (1-5): 3-8):1 in the lactic acid bacteria may be, for example, 1:3:1, 1:5:1, 2:3:1, 2:4:1, 3:3:1, 3:6:1, 4:3:1, 4:7:1, 5:3:1, 5:4:1, 5:8:1, preferably 3:5: 1.
According to the invention, the bifidobacterium accounts for 5-10 parts by weight of the expandable vaginal suppository. For example, it may be 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts.
According to the invention, the weight ratio of bifidobacterium lactis to bifidobacterium bifidum in the bifidobacterium is (3-8) to (1-5), and can be, for example, 3:1, 3:2, 3:5, 4:1, 4:3, 4:5, 5:1, 5:3, 5:5, 6:1, 6:3, 6:5, 7:1, 7:3, 7:5, 8:1, 8:3, 8:5, preferably 5: 3.
The inventor unexpectedly finds that in the vaginal dilation suppository, lactobacillus acidophilus, lactobacillus fermentum, lactobacillus bulgaricus and lactobacillus bulgaricus form a lactobacillus mixture, and by adding bifidobacterium and streptococcus coli, the bacteria generate a synergistic interaction effect, and the inhibition effect on HSV is remarkable.
In a second aspect, the present invention provides a method of preparing a vaginal dilation suppository according to the first aspect, comprising the steps of:
(1) putting the matrix in a water bath for heating and melting to obtain a melt;
(2) uniformly mixing lactic acid bacteria and bifidobacteria, and then mixing with the melt in the step (1) to obtain a mixture;
(3) pouring the mixture obtained in the step (2) into a plug mold, inserting an expansion carrier, and cooling and shaping to obtain a matrix plug core;
(4) fully mixing the recombinant human interferon and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix plug core in the step (3) in a spraying mode, and cooling to prepare the suppository;
(5) and (4) adding the suppository in the step (4) into a high molecular polymer, performing ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Compared with the prior art, the invention has the following beneficial effects:
(1) the expandable vaginal suppository provided by the invention can balance various bacterial communities in the vagina due to the adoption of the lactic acid bacteria and the bifidobacteria as active ingredients, has broad spectrum for treating vaginitis, and can fundamentally prevent and treat vaginitis diseases; by adopting the specific microbial agent combination, the bacteria can play a remarkable synergistic effect, and the inhibition effect on HSV is remarkable;
(2) the expansion value of the vaginal expansion suppository is more than 1.7, and the weight difference is less than +/-10%, wherein the maximum axial expansion value is 2.03, the maximum radial expansion value is 2.02, and the minimum weight difference is +/-0.01%;
(3) the outer layer of the vaginal expansion suppository is coated with the high molecular polymer, so that the activity and the stability of the vaginal expansion suppository are improved, and the vaginal expansion suppository can still keep 2.6 × 10 after being placed at 37 ℃ for 2 years8IU/piece of in vitro activity, placing for 6 months in the environment with the humidity of 65% +/-5%, the maximum labeled amount of the recombinant human interferon is 99.99%, and the fusion time is stabilized at 25 min;
(4) the outer layer of the vaginal expansion suppository is coated with the high molecular polymer, so that the release speed and the release time of the recombinant human interferon are effectively controlled, and the drug effect duration of the vaginal expansion suppository can reach 24 hours at most;
(5) the invention improves the curative effect of the recombinant human interferon by 3-4 times under the coordination of the schisandra extract, the human placenta extract, the wild lily extract and the scutellaria extract.
Detailed Description
To further illustrate the technical means and effects of the present invention, the present invention is further described with reference to the following examples. It is to be understood that the specific embodiments described herein are merely illustrative of the invention and are not limiting of the invention.
The examples do not show the specific techniques or conditions, according to the technical or conditions described in the literature in the field, or according to the product specifications. The reagents or apparatus used are conventional products commercially available from normal sources, not indicated by the manufacturer.
Example 1
The preparation method comprises the following steps:
(1) putting the matrix in a water bath for heating and melting to obtain a melt;
(2) uniformly mixing lactic acid bacteria and bifidobacteria, and then mixing with the melt in the step (1) to obtain a mixture;
(3) pouring the mixture obtained in the step (2) into a plug mold, inserting an expansion carrier, and cooling and shaping to obtain a matrix plug core;
(4) fully mixing the recombinant human interferon and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix plug core in the step (3) in a spraying mode, and cooling to prepare the suppository;
(5) and (4) adding the suppository in the step (4) into a high molecular polymer, performing ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Example 2
Compared with the embodiment 1, the components of the recombinant human interferon and the traditional Chinese medicine composition are adjusted, and the content of each component is the same as that of the embodiment 1.
The preparation method is the same as example 1.
Example 3
Compared with the embodiment 1, the components of the recombinant human interferon and the traditional Chinese medicine composition are adjusted, and the content of each component is the same as that of the embodiment 1.
The preparation method is the same as example 1.
Comparative example 1
Compared with the example 1, the recombinant interferon is not contained, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Comparative example 2
Compared with the embodiment 1, the traditional Chinese medicine composition is not contained, and the content of each component is the same as that of the embodiment 1.
The preparation method is the same as example 1.
Comparative example 3
Compared with the example 1, the Chinese magnoliavine fruit extract is not contained, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Comparative example 4
Compared with example 1, the beverage does not contain human placenta extract, and the content of each component is the same as that of example 1.
The preparation method is the same as example 1.
Comparative example 5
Compared with the example 1, the lily extract is not contained, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Comparative example 6
Compared with the example 1, the composition does not contain the scutellaria baicalensis extract, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Example 4
Compared with the example 1, the composition of the synthetic fatty acid ester, the hydrogenated oil and the colloidal compound in the matrix is adjusted to be 2:10:1 by weight, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Example 5
Compared with the example 1, the composition of the synthetic fatty acid ester, the hydrogenated oil and the colloidal compound in the matrix is adjusted to be 6:12:1 by weight, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Example 6
Compared with the example 1, the component composition of the matrix is adjusted, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Comparative example 7
Compared with the example 1, the components of the slow release agent are adjusted, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Comparative example 8
Compared with the example 1, the components of the slow release agent are adjusted, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Example 7
Compared with the example 1, the lactobacillus acidophilus, the lactobacillus fermentum and the lactobacillus bulgaricus in the lactobacillus are adjusted to be composed of components with the mass ratio of 1:3:1, and the content of each component is the same as that in the example 1.
The preparation method is the same as example 1.
Example 8
Compared with the example 1, the lactobacillus acidophilus, the lactobacillus fermentum and the lactobacillus bulgaricus in the lactobacillus are adjusted to be composed of components with the mass ratio of 5:8:1, and the content of each component is the same as that in the example 1.
The preparation method is the same as example 1.
Example 9
Compared with the example 1, the component composition of the lactobacillus bifidus and the bifidobacterium bifidum in the lactobacillus with the mass ratio of 3:1 is adjusted, and the content of each component is the same as that in the example 1.
The preparation method is the same as example 1.
Example 10
Compared with the example 1, the component composition of the lactobacillus bifidus and the bifidobacterium bifidum in the lactobacillus with the mass ratio of 8:5 is adjusted, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Comparative example 9
Compared with the example 1, the lactic acid bacteria are not contained, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Comparative example 10
Compared with the example 1, the lactobacillus acidophilus, the lactobacillus fermentum and the lactobacillus bulgaricus in the lactobacillus are adjusted to be composed of components with the mass ratio of 6:2:1, and the content of each component is the same as that in the example 1.
The preparation method is the same as example 1.
Comparative example 11
Compared with the example 1, the composition does not contain bifidobacteria, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Comparative example 12
Compared with the example 1, the component composition of the lactobacillus bifidus and the bifidobacterium bifidum in the lactobacillus with the mass ratio of 1:3 is adjusted, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Example 11
Compared with the example 1, the component composition is adjusted, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Example 12
Compared with the example 1, the component composition is adjusted, and the content of each component is the same as that of the example 1.
The preparation method is the same as example 1.
Swelling value and weight Difference measurement experiment
The measurement of the axial expansion value, the radial expansion value and the weight difference were carried out for the expandable vaginal suppositories of examples 1 to 12.
(1) Method for measuring axial expansion value
1) Selecting one point or a plurality of points along the radial direction of the end surface of the vaginal expansion suppository, measuring the initial length H of the expansion carrier, and rolling for a plurality of times at different angles to obtain the initial average length Hi;
2) after the vaginal expansion suppository is subjected to melting time limit detection, measuring the expansion length h of the expansion carrier at the position selected in the step 1), and rolling for a plurality of times at different angles to obtain the average expanded length hi;
3) and calculating the axial expansion value of the vaginal expansion suppository according to pi ═ Hi/Hi.
(2) Method for measuring radial expansion value
1) Selecting one point or a plurality of points along the axial direction of the end surface of the vaginal expansion suppository, measuring the initial diameter R of the expansion carrier, and rolling for a plurality of times at different angles to obtain the initial average diameter Ri;
2) after the vaginal expansion suppository is subjected to fusion time limit detection, measuring the expansion length r of the expansion carrier at the position selected in the step 1'), and measuring for a plurality of times by rolling at different angles to obtain the average length ri after expansion;
3) and calculating the radial expansion value of the vaginal expansion suppository according to Pi-Ri/Ri.
(3) Weight difference measuring method
1) Weighing the initial weight M of the vaginal expansion suppository;
2) scraping off the high molecular polymer, the medicament and the matrix, putting the expanded carrier into an organic solvent at the temperature of 20-90 ℃, taking out, drying at the temperature of 50-150 ℃ for 1-10h, and weighing the weight m;
3) calculating the total weight X of the high molecular polymer, the medicament and the matrix according to the formula of X-M.
The results are shown in Table 1.
TABLE 1 dilation values and weight differences for vaginal dilation tampons
As can be seen from Table 1, the expandable vaginal plugs of examples 1-12 all had axial/radial expansion values greater than 1.7 and weight differences less than + -1%, and the results were acceptable, as can be seen from examples 4-6, with the change in the weight ratio of the synthetic fatty acid ester, the hydrogenated oil, and the colloid compound in the matrix, the axial/radial expansion values decreased, and with the use of matrices other than the synthetic fatty acid ester, the hydrogenated oil, and the colloid compound in the matrix, the axial/radial expansion values decreased.
In vitro Activity assay
The in vitro activity of the vaginal expansion suppositories of examples 1 to 12 after being left at 4 ℃, 25 ℃ and 37 ℃ for 2 years was determined using the MTT colorimetric method, with initial titer of 5.2 × 108IU/piece, results are shown in Table 2.
TABLE 2 in vitro Activity of recombinant human Interferon in vaginal dilation tampons
The expandable vaginal suppository of examples 1-12 was placed at 4 ℃ for two years, the in vitro activity of the expandable vaginal suppository was not changed, and was only slightly decreased at 25 ℃ and 37 ℃ for two years, wherein the expandable vaginal suppository of example 1 still maintained high activity at 4 ℃, 25 ℃ and 37 ℃ for two years, as can be seen from comparative examples 7-8, the outer layer coated with too little polymer, too fast recombinant human interferon activity, too many outer layer coated polymer, too slow recombinant human interferon activity, and too long drug release time, therefore, the outer layer coated polymer of the expandable vaginal suppository can effectively ensure the activity of recombinant human interferon, and has protective effect on recombinant human interferon and Chinese medicinal compositions.
Stability test
The expandable vaginal suppositories of examples 1 to 12 and comparative examples 7 to 8 were left for 6 months under a constant condition of 25 ℃. + -. 2 ℃ and a relative humidity of 65%. + -. 5%, and the properties of the expandable vaginal suppositories, the labeled amount (%) of recombinant human interferon and the fusion time period were measured as specified in the Chinese pharmacopoeia, and the results are shown in Table 3.
TABLE 3 stability of recombinant human interferon in vaginal dilation tampons
| Numbering | Traits | Indicating amount (%) | Integration time limit (min) |
| Example 1 | Yellow, smooth, unbroken | 99.99 | 25 |
| Example 2 | Yellow, smooth, unbroken | 99.98 | 25 |
| Example 3 | Yellow, smooth, unbroken | 99.96 | 24 |
| Example 4 | Yellow, smooth, unbroken | 99.95 | 23 |
| Example 5 | Yellow, smooth, unbroken | 99.92 | 25 |
| Example 6 | Yellow, smooth, unbroken | 99.90 | 22 |
| Example 7 | Yellow, smooth, unbroken | 99.95 | 23 |
| Example 8 | Yellow, smooth and unbrokenCrack (crack) | 99.93 | 25 |
| Example 9 | Yellow, smooth, unbroken | 99.90 | 24 |
| Example 10 | Yellow, smooth, unbroken | 99.90 | 23 |
| Example 11 | Yellow, smooth, unbroken | 99.89 | 25 |
| Example 12 | Yellow, smooth, unbroken | 99.92 | 22 |
| Comparative example 7 | Yellow brown, rough, cracked, blotchy | 85.01 | - |
| Comparative example 8 | Yellow, smooth, unbroken | 99.99 | 10 |
The vaginal dilation suppository of the embodiments 1-6 is placed for 6 months under the constant conditions that the temperature is 25 ℃ +/-2 ℃ and the relative humidity is 65% +/-5%, the color is not changed, the surface is smooth, the characters such as rupture and long spots are not changed, the marked quantity is not obviously changed, the fusion time limit is not basically prolonged, and the comparative examples 7-8 show that the outer-layer coated high molecular polymer is too little, the activity of the recombinant human interferon is lost and cannot reach the drug effect, the outer-layer coated high molecular polymer is too much, the release of the recombinant human interferon is too fast, and the drug cannot be absorbed in time, so the outer-layer coated high molecular polymer of the vaginal dilation suppository can effectively ensure the stability of the recombinant human interferon, and has the protection effect on the recombinant human interferon and the traditional Chinese medicine composition.
Test for duration of drug action
The results of the drug release time of the expandable vaginal suppositories of examples 1 to 12 and comparative examples 1 to 2 are shown in Table 4.
TABLE 4 drug Release time for vaginal dilation suppository
| Numbering | Release time (h) | Numbering | Release time (h) |
| Example 1 | 24 | Example 8 | 20 |
| Example 2 | 22 | Example 9 | 21 |
| Example 3 | 23 | Example 10 | 20 |
| Example 4 | 20 | Example 11 | 16 |
| Example 5 | 21 | Example 12 | 17 |
| Example 6 | 18 | Comparative example 7 | 6 |
| Example 7 | 19 | Comparative example 8 | 48 |
The drug effect of the vaginal dilation suppository of examples 1-12 can last for more than 16 hours, wherein the drug effect of the vaginal dilation suppository of example 1 lasts for the longest time, up to 24 hours; compared with the example 1, the vaginal dilation suppository of the comparative examples 7 to 8 is coated with too little high molecular polymer, the drug is released too fast and is not easy to absorb, the vaginal dilation suppository is coated with too much high molecular polymer, the recombinant human interferon is released too slowly, the drug effect time is too long, and the drug effect is too slow.
anti-HSV 1 and HSV2 experiments
To 96-well cell culture platesAdding 0.1m L/well cell suspension, removing the culture solution after the cells adhere to the wall, adding 0.1m L virus and 0.1m L test solution into each well, mixing the test solution according to the proportion of the recombinant human interferon and the Chinese medicinal composition described in examples 1-12 and comparative examples 1-12, placing 96-well cell culture plate at 37 ℃ and 5% CO2In an incubator for 24 hours, the TCID is measured and calculated by a conventional method50The potency was inhibited and the results are shown in table 5.
TABLE 5 inhibitory Effect of recombinant human Interferon HSV1 and HSV2
It can be seen from examples 1-12 and comparative examples 1-6 that interferon has an inhibitory effect on HSV, and the traditional Chinese medicine composition of the schisandra extract, the human placenta extract, the lilium brownii extract and the scutellaria extract has a significant synergistic effect on recombinant human interferon, the recombinant human interferon and the traditional Chinese medicine composition are jointly applied and are mutually synergistic, the inhibitory effect of the recombinant human interferon on HSV is enhanced by 3-4 times, and when the recombinant human interferon is 0.5 part, the schisandra extract is 8 parts, the human placenta extract is 15 parts, the lilium brownii extract is 6 parts and the scutellaria extract is 6 parts, the synergistic effect of the recombinant human interferon and the traditional Chinese medicine composition is optimal, and the inhibitory effect on HSV is most significant.
As can be seen from examples 1 to 12 and comparative examples 9 to 12, the interferon has an inhibitory effect on HSV, and when the weight ratio of Lactobacillus acidophilus, Lactobacillus fermentum and Lactobacillus bulgaricus to Lactobacillus bulgaricus in lactobacillus is 3:5:1 and the weight ratio of Bifidobacterium lactis to Bifidobacterium bifidum in Bifidobacterium is 5:3, the inhibitory effect is most significant, and the inhibitory effect on HSV is most significant.
In conclusion, the swelling value of the vaginal swelling suppository is greater than 1.7, the weight difference is less than +/-10%, the outer layer of the vaginal swelling suppository is coated with the high molecular polymer, the in vitro activity and stability of the recombinant human interferon are improved, the release speed and the release time of the active ingredients are controlled, the side effect of the recombinant human interferon is reduced, and the curative effect of the recombinant human interferon is improved by 3-4 times under the coordination of the traditional Chinese medicine composition consisting of the sophora flavescens extract, the phellodendron extract, the radix scutellariae extract and the poria cocos extract.
The applicant states that the present invention is illustrated in detail by the above examples, but the present invention is not limited to the above detailed methods, i.e. it is not meant that the present invention must rely on the above detailed methods for its implementation. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.
Claims (9)
1. The vaginal expansion suppository is characterized by comprising the following components in parts by weight: 0.1-1.0 part of recombinant human interferon, 10-50 parts of high molecular polymer, 50-200 parts of matrix, 500 parts of swelling carrier, 5-10 parts of schisandra extract, 8-20 parts of placenta hominis extract, 1-10 parts of wild lily extract, 1-10 parts of scutellaria extract, 25 parts of lactic acid bacteria and 6 parts of bifidobacterium;
the lactobacillus is lactobacillus acidophilus, lactobacillus fermentum and lactobacillus bulgaricus in a weight ratio of 3:5: 1;
the bifidobacterium is bifidobacterium lactis and bifidobacterium bifidum in a weight ratio of 5: 3;
heating and melting the matrix in water bath to obtain melt, mixing lactobacillus and bifidobacterium uniformly, mixing with the melt to obtain a mixture, pouring the mixture into a plug mold, inserting a swelling carrier, and cooling and shaping to obtain a matrix plug core;
the recombinant human interferon, the Chinese medicinal composition schisandra extract, the human placenta extract, the wild lily extract and the scutellaria extract are fully mixed and sprayed on the surface of the matrix plug in a spraying mode;
the high molecular polymer is coated on the outer layer of the vaginal expansion suppository.
2. The expandable vaginal suppository of claim 1, wherein the high molecular weight polymer comprises any one of polylactic acid, polycaprolactone, polylactic-co-glycolic acid, or polyurethane.
3. The expandable vaginal suppository of claim 2, wherein the high molecular weight polymer is a polylactic-co-glycolic acid.
4. The expandable vaginal suppository of claim 1, wherein the matrix comprises any one or more of synthetic fatty acid esters, natural fatty acid esters, hydrogenated oils, lipid matrices or colloidal compounds.
5. The expandable vaginal suppository of claim 4, wherein the matrix is a combination of synthetic fatty acid esters, hydrogenated oils and colloidal compounds.
6. The expandable vaginal suppository of claim 5, wherein the weight ratio of the synthetic fatty acid ester, the hydrogenated oil and the colloidal compound is 5:12: 1.
7. The expandable vaginal suppository of claim 1 wherein the expandable carrier is a combination of nylon, viscose and acrylic.
8. The expandable vaginal suppository as claimed in claim 7, wherein the mass ratio of the nylon, the viscose and the acrylic is 5:2: 3.
9. A method of preparing a vaginal expansion suppository as claimed in any one of claims 1 to 8, comprising the steps of:
(1) putting the matrix in a water bath for heating and melting to obtain a melt;
(2) uniformly mixing lactic acid bacteria and bifidobacteria, and then mixing with the melt in the step (1) to obtain a mixture;
(3) pouring the mixture obtained in the step (2) into a plug mold, inserting an expansion carrier, and cooling and shaping to obtain a matrix plug core;
(4) fully mixing the recombinant human interferon and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix plug core in the step (3) in a spraying mode, and cooling to prepare the suppository;
(5) and (4) adding the suppository in the step (4) into a high molecular polymer, performing ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
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| CN111420033A (en) * | 2020-03-30 | 2020-07-17 | 温州肯恩大学(Wenzhou-KeanUniversity) | Use of human interferon in tumor treatment |
| CN111358938B (en) * | 2020-03-30 | 2023-08-11 | 温州肯恩大学(Wenzhou-KeanUniversity) | Human interferon-epsilon and interferon-gamma combined medicine and application |
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