CN107583036B - Recombinant human interferon α 1b vaginal expansion suppository and preparation method thereof - Google Patents
Recombinant human interferon α 1b vaginal expansion suppository and preparation method thereof Download PDFInfo
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- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a recombinant human interferon α b vaginal expansive suppository and a preparation method thereof, wherein the vaginal expansive suppository comprises 0.01-1.0 part of recombinant human interferon α b, 10-50 parts of high molecular polymer, 50-200 parts of matrix and 500 parts of expansion carrier 100-.
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 α 1b vaginal expansion suppository and a preparation method thereof.
Background
The recombinant human interferon α 1b is a multifunctional high-activity induced protein generated by Chinese healthy human leucocytes and lymphocytes, has obvious broad-spectrum antiviral action and immunoregulation function, has obvious curative effect on vaginitis, has small side effect, and is suitable for Chinese physique at present, the dosage form of the recombinant human interferon α 1b is mainly tablets and suppositories, but the recombinant human interferon α 1b is easily decomposed by light and moisture, the development difficulty of a new dosage form is high, and the wide application of the recombinant human interferon α 1b 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 α 1b vaginal expansive suppository and the preparation method thereof are provided, so that the expansive suppository not only has a remarkable treatment effect on vaginitis, but also has a lasting curative effect and small toxic and side effects, 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 α 1b expandable vaginal suppository and the preparation method thereof, the expandable vaginal suppository uses the recombinant human interferon α 1b which is suitable for the constitution of Chinese people as a main active ingredient, and the outer layer of the expandable vaginal suppository is coated with a high molecular polymer, so that the expandable vaginal suppository has a remarkable curative effect and small toxic and side effects.
In a first aspect, the invention provides a vaginal expansion suppository, which comprises, by weight, 0.01-1.0 part of recombinant human interferon α 1b, 10-50 parts of high molecular polymer, 50-200 parts of matrix and 100-500 parts of expansion carrier.
The vaginal dilation suppository provided by the invention adopts the recombinant human interferon α 1b as a main active ingredient, is suitable for Chinese physique, is coated with a high molecular polymer at the outer layer, controls the release speed and action time of the active ingredient, reduces the daily administration times, enables the recombinant human interferon α 1b to be better absorbed, distributed and metabolized by human bodies, and fully exerts the remarkable curative effect.
Preferably, the recombinant human interferon α 1b is 0.01-1.0 part by weight, such as 0.01 part, 0.05 part, 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 0.05-0.5 part, and more preferably 0.1 part.
Preferably, 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.
Preferably, 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.
Preferably, 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.
Preferably, the vaginal expansion suppository further comprises a traditional Chinese medicine composition.
The traditional Chinese medicine extract and the recombinant human interferon α 1b have obvious synergistic effect in the aspect of treating vaginitis, and after the traditional Chinese medicine composition is added, the treatment effect of the recombinant human interferon α 1b on female vaginitis is obviously improved, 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.
Preferably, the traditional Chinese medicine composition comprises the following components in parts by weight: 5-20 parts of lithospermum extract, 5-10 parts of Chinese violet extract, 1-10 parts of amethyst extract and 1-10 parts of human placenta extract.
Preferably, the weight portion of the lithospermum extract is 5 to 20 portions, such as 5 portions, 6 portions, 7 portions, 8 portions, 9 portions, 10 portions, 11 portions, 12 portions, 13 portions, 14 portions, 15 portions, 16 portions, 17 portions, 18 portions, 19 portions or 20 portions, preferably 10 to 18 portions, and more preferably 15 portions.
Preferably, the part by weight of the Chinese violet extract is 5-10 parts, such as 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, preferably 5-9 parts, and more preferably 8 parts.
Preferably, the weight part of the amethyst 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 2 to 8 parts, and more preferably 5 parts.
Preferably, the weight part of the human placenta extract is 1 to 10 parts, such as 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, preferably 2 to 8 parts, and more preferably 5 parts.
Preferably, the vaginal expansion suppository comprises, by weight, 0.05-0.5 part of recombinant human interferon α 1b, 10-18 parts of lithospermum extract, 5-9 parts of Chinese violet extract, 2-8 parts of amethyst extract, 2-8 parts of human placenta extract, 30-50 parts of high molecular polymer, 80-150 parts of matrix and 400 parts of expansion carrier.
Preferably, the vaginal expansive suppository comprises, by weight, 0.1 part of recombinant human interferon α 1b, 15 parts of lithospermum extract, 8 parts of Chinese violet herb extract, 5 parts of amethyst extract, 5 parts of human placenta extract, 35 parts of high molecular polymer, 120 parts of matrix and 300 parts of expansive carrier.
Preferably, the high molecular polymer includes any one or a combination of at least two of polylactic acid, polycaprolactone, 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.
Preferably, the matrix comprises any one or a combination of at least two of synthetic fatty acid esters, natural fatty acid esters, lipid matrices or colloidal compounds, and may be, for example, a combination of synthetic fatty acid esters and natural fatty acid esters, a combination of synthetic fatty acid esters and lipid matrices, a combination of synthetic fatty acid esters and colloidal compounds, a combination of natural fatty acid esters and lipid matrices, a combination of natural fatty acid esters and colloidal compounds, or a combination of lipid matrices and colloidal compounds, preferably a combination of synthetic fatty acid esters and colloidal compounds.
Preferably, the weight ratio of the synthetic fatty acid ester to the colloidal compound is (1-10: 1), and may be, for example, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1, preferably (2-10: 1), and more preferably 5: 1.
Preferably, the swelling carrier comprises any one or a combination of at least two of a tampon, a nonwoven or an elastic fiber, which may be, for example, a combination of a tampon and a nonwoven, a combination of a tampon and an elastic fiber, a combination of a nonwoven and an elastic fiber, or a combination of a tampon, a nonwoven and an elastic fiber, preferably a tampon.
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) pouring the melt obtained in the step (1) into a plug mold, inserting an expansion carrier, and cooling and shaping to obtain a matrix plug core;
(3) fully mixing the recombinant human interferon α 1b and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix suppository core obtained in the step (2) in a spraying mode, and cooling to obtain the suppository;
(4) and (4) adding the suppository in the step (3) into a high molecular polymer, performing ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Preferably, the temperature of the water bath in step (1) is 60-70 deg.C, such as 60 deg.C, 61 deg.C, 62 deg.C, 63 deg.C, 64 deg.C, 65 deg.C, 66 deg.C, 67 deg.C, 68 deg.C, 69 deg.C or 70 deg.C.
Preferably, the temperature of step (3) is 35-45 deg.C, such as 35 deg.C, 36 deg.C, 37 deg.C, 38 deg.C, 39 deg.C, 40 deg.C, 41 deg.C, 42 deg.C, 43 deg.C, 44 deg.C or 45 deg.C.
Compared with the prior art, the invention has the following beneficial effects:
(1) the expansion value of the vaginal expansion suppository is more than 1.5, and the weight difference is less than +/-10%, wherein the axial expansion value is maximum 1.92, the radial expansion value is maximum 1.91, and the weight difference is minimum +/-0.02%;
(2) the outer layer of the vaginal expansion suppository is coated with high molecular polymer, so that the activity and stability of the vaginal expansion suppository are improved, and the vaginal expansion suppository can still maintain 1.7 multiplied by 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 α 1b is 100.01%, and the fusion time is stabilized at 25 min;
(3) the outer layer of the vaginal expansion suppository is coated with high molecular polymer, so that the release speed and the release time of the recombinant human interferon α 1b are effectively controlled, and the drug effect duration of the vaginal expansion suppository is up to 24 hours at most;
(4) the curative effect of the recombinant human interferon α 1b is remarkably improved under the coordination of the traditional Chinese medicine composition consisting of the lithospermum extract, the Chinese violet extract, the amethyst extract and the human placenta 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
In the embodiment, the vaginal expansive suppository comprises, by weight, 0.1 part of recombinant human interferon α 1b, 15 parts of lithospermum extract, 8 parts of Chinese violet herb extract, 5 parts of amethyst extract, 5 parts of human placenta extract, 35 parts of polylactic acid-glycolic acid copolymer, 120 parts of a mixture of synthetic fatty acid ester and a colloidal compound and 300 parts of cotton sliver.
The preparation method comprises the following steps:
(1) mixing synthetic fatty acid ester and colloid compound at a weight ratio of 5:1, and heating and melting in 65 deg.C water bath to obtain melt;
(2) pouring the melt obtained in the step (1) into a plug mold, inserting a cotton sliver, cooling and shaping to obtain a matrix plug core;
(3) fully mixing the recombinant human interferon α 1b and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix suppository core obtained in the step (2) in a spraying mode, and cooling to 40 ℃ to obtain a suppository;
(4) and (4) adding the suppository in the step (3) into polylactic acid-glycolic acid copolymer for ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Example 2
In the embodiment, the vaginal expansion suppository comprises, by weight, 0.05 part of recombinant human interferon α 1b, 18 parts of lithospermum extract, 5 parts of Chinese violet extract, 8 parts of amethyst extract, 2 parts of human placenta extract, 50 parts of polylactic acid, 80 parts of a mixture of synthetic fatty acid ester and natural fatty acid ester and 400 parts of non-woven fabric.
The preparation method comprises the following steps:
(1) mixing synthetic fatty acid ester and natural fatty acid ester at a weight ratio of 6:1, and heating and melting in 64 deg.C water bath to obtain melt;
(2) pouring the melt obtained in the step (1) into a plug mold, inserting non-woven fabric, cooling and shaping to obtain a matrix plug core;
(3) fully mixing the recombinant human interferon α 1b and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix suppository core obtained in the step (2) in a spraying mode, and cooling to 41 ℃ to obtain a suppository;
(4) and (4) adding the suppository in the step (3) into polylactic acid for ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Example 3
In the embodiment, the vaginal expansion suppository comprises 0.5 part of recombinant human interferon α 1b, 10 parts of lithospermum extract, 9 parts of Chinese violet extract, 2 parts of amethyst extract, 8 parts of human placenta extract, 30 parts of polycaprolactone, 150 parts of a mixture of synthetic fatty acid ester and lipid matrix and 150 parts of elastic fiber in parts by weight.
The preparation method comprises the following steps:
(1) mixing synthetic fatty acid ester and lipid matrix at weight ratio of 2:1, heating in 68 deg.C water bath for melting to obtain melt;
(2) pouring the melt obtained in the step (1) into a plug mold, inserting elastic fibers, and cooling and shaping to obtain a matrix plug core;
(3) fully mixing the recombinant human interferon α 1b and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix suppository core obtained in the step (2) in a spraying mode, and cooling to 37 ℃ to obtain a suppository;
(4) and (4) adding the suppository in the step (3) into polycaprolactone, performing ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Example 4
In the embodiment, the vaginal expansion suppository comprises 0.01 part of recombinant human interferon α 1b, 20 parts of lithospermum extract, 5 parts of Chinese violet extract, 10 parts of amethyst extract, 1 part of human placenta extract, 50 parts of polyurethane, 50 parts of mixture of natural fatty acid ester and lipid matrix and 500 parts of cotton sliver in parts by weight.
The preparation method comprises the following steps:
(1) mixing natural fatty acid ester and lipid matrix at weight ratio of 10:1, and heating and melting in water bath at 60 deg.C to obtain melt;
(2) pouring the melt obtained in the step (1) into a plug mold, inserting a cotton sliver, cooling and shaping to obtain a matrix plug core;
(3) fully mixing the recombinant human interferon α 1b and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix suppository core obtained in the step (2) in a spraying mode, and cooling to 45 ℃ to obtain the suppository;
(4) and (4) adding the suppository in the step (3) into polyurethane, performing ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Example 5
In the embodiment, the vaginal expansion suppository comprises, by weight, 1 part of recombinant human interferon α 1b, 5 parts of lithospermum extract, 10 parts of Chinese violet extract, 1 part of amethyst extract, 10 parts of human placenta extract, 10 parts of polylactic acid-polycaprolactone copolymer, 200 parts of a mixture of natural fatty acid ester and a colloidal compound, and 100 parts of non-woven fabric.
The preparation method comprises the following steps:
(1) mixing natural fatty acid ester and colloid compound at a weight ratio of 1:1, and heating and melting in 70 deg.C water bath to obtain melt;
(2) pouring the melt obtained in the step (1) into a plug mold, inserting non-woven fabric, cooling and shaping to obtain a matrix plug core;
(3) fully mixing the recombinant human interferon α 1b and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix suppository core obtained in the step (2) in a spraying mode, and cooling to 35 ℃ to obtain a suppository;
(4) and (4) adding the suppository in the step (3) into polylactic acid-polycaprolactone copolymer for ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Example 6
Compared with the embodiment 1, in the embodiment, except for not comprising the traditional Chinese medicine composition, the vaginal expansion suppository comprises 0.1 part of recombinant human interferon α 1b, 35 parts of polylactic acid-glycolic acid copolymer, 120 parts of a mixture of synthetic fatty acid ester and colloid compound and 300 parts of cotton sliver in parts by weight, and other preparation processes are the same as the embodiment 1.
Comparative example 1
Compared with the embodiment 1, in the embodiment, the vaginal expansive suppository comprises 0.1 part of recombinant human interferon α 1b, 15 parts of lithospermum extract, 8 parts of Chinese violet herb extract, 5 parts of amethyst extract, 5 parts of human placenta extract, 120 parts of a mixture of synthetic fatty acid ester and colloidal compound and 300 parts of cotton sliver in parts by weight except that polylactic acid-glycolic acid copolymer is not included, and other preparation processes are the same as the embodiment 1.
Comparative example 2
Compared with example 1, in this example, the preparation method of the vaginal expansion suppository comprises the following steps:
(1) mixing synthetic fatty acid ester and colloid compound at a weight ratio of 5:1, and heating and melting in 65 deg.C water bath to obtain melt;
(2) adding the traditional Chinese medicine composition into the melt in the step (1), and cooling to 40 ℃ to obtain a mixture;
(3) adding recombinant human interferon α 1b into the mixture obtained in the step (2) to prepare a drug-containing matrix;
(4) pouring the drug-containing matrix obtained in the step (3) into a suppository mold, inserting a cotton sliver, cooling and shaping to obtain a suppository;
(5) and (5) adding the suppository in the step (4) into polylactic acid-glycolic acid copolymer for ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
Comparative example 3
Compared with the embodiment 1, in the embodiment, the vaginal expansive suppository comprises, by weight, 0.1 part of recombinant human interferon α 2a, 15 parts of lithospermum extract, 8 parts of Chinese violet herb extract, 5 parts of amethyst extract, 5 parts of human placenta extract, 35 parts of polylactic acid-glycolic acid copolymer, 120 parts of a mixture of synthetic fatty acid ester and colloidal compound and 300 parts of cotton sliver, and other preparation processes are the same as the embodiment 1.
Comparative example 4
Compared with the embodiment 1, in the embodiment, the vaginal expansive suppository comprises, by weight, 0.1 part of recombinant human interferon α 2b, 15 parts of lithospermum extract, 8 parts of Chinese violet herb extract, 5 parts of amethyst extract, 5 parts of human placenta extract, 35 parts of polylactic acid-glycolic acid copolymer, 120 parts of a mixture of synthetic fatty acid ester and colloidal compound and 300 parts of cotton sliver, and other preparation processes are the same as the embodiment 1.
Comparative example 5
Compared with the embodiment 1, in the embodiment, the vaginal expansive suppository comprises 0.005 parts of recombinant human interferon α 1b, 25 parts of lithospermum extract, 1 part of Chinese violet extract, 15 parts of amethyst extract, 0.5 part of human placenta extract, 60 parts of polylactic acid-glycolic acid copolymer, 30 parts of a mixture of synthetic fatty acid ester and colloidal compound and 550 parts of cotton sliver in parts by weight, and other preparation processes are the same as the embodiment 1.
Comparative example 6
Compared with the embodiment 1, in the embodiment, the vaginal expansive suppository comprises 5 parts by weight of recombinant human interferon α 1b, 1 part by weight of lithospermum extract, 15 parts by weight of Chinese violet herb extract, 0.5 part by weight of amethyst extract, 15 parts by weight of human placenta extract, 5 parts by weight of polylactic acid-glycolic acid copolymer, 220 parts by weight of a mixture of synthetic fatty acid ester and colloidal compound and 80 parts by weight of cotton sliver, and other preparation processes are the same as the embodiment 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 6.
(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
| Numbering | Axial expansion value | Radial expansion value | Difference in weight |
| Example 1 | 1.92 | 1.91 | ±0.02％ |
| Example 2 | 1.88 | 1.87 | ±0.13％ |
| Example 3 | 1.87 | 1.88 | ±0.12％ |
| Example 4 | 1.82 | 1.84 | ±0.27％ |
| Example 5 | 1.82 | 1.82 | ±0.25％ |
| Example 6 | 1.79 | 1.80 | ±0.28％ |
The axial/radial expansion values of the vaginal expansion bolts of examples 1-6 are all greater than 1.5, the weight difference is less than +/-10%, and the results are acceptable.
In vitro Activity assay
The swelling suppositories of examples 1 to 6 and comparative examples 1 to 6 were measured for in vitro activity after being left at 4 ℃, 25 ℃ and 37 ℃ for 2 years using the MTT colorimetry, and the initial titer was 5.2X 108IU/piece, results are shown in Table 2.
TABLE 2 in vitro Activity of recombinant human interferon α 1b in vaginal dilation tampons
| Numbering | 4℃ | 25℃ | 37℃ |
| Example 1 | 5.1×108 | 3.6×108 | 1.7×108 |
| Example 2 | 4.9×108 | 3.1×108 | 8.4×107 |
| Example 3 | 4.9×108 | 2.9×108 | 8.5×107 |
| Example 4 | 4.7×108 | 2.2×108 | 7.8×107 |
| Example 5 | 4.8×108 | 2.0×108 | 7.8×107 |
| Example 6 | 4.4×108 | 1.8×108 | 7.1×107 |
| Comparative example 1 | 3.7×107 | 2.9×104 | 5.5×102 |
| Comparative example 2 | 4.0×107 | 3.5×104 | 5.0×102 |
| Comparative example 3 | 2.5×108 | 6.3×107 | 1.0×107 |
| Comparative example 4 | 2.8×108 | 7.2×107 | 2.1×107 |
| Comparative example 5 | 3.8×108 | 1.0×108 | 9.2×107 |
| Comparative example 6 | 3.6×108 | 1.2×108 | 9.5×107 |
The expandable vaginal suppository of examples 1-6 has substantially no change in vitro activity when placed at 4 ℃ for two years, and has only slightly reduced in vitro activity when placed at 25 ℃ and 37 ℃ for two years, wherein the expandable vaginal suppository of example 1 still can maintain higher activity when placed at 4 ℃, 25 ℃ and 37 ℃ for two years.
Compared with example 1, the activity of the expandable vaginal suppository of comparative examples 1-2 is slightly reduced after being placed at 4 ℃ for two years, and the activity is basically disappeared after being placed at 37 ℃ for two years, so that the expandable vaginal suppository cannot be used; the expandable vaginal suppositories of comparative examples 3-6 are less active than those of examples 1-6.
Stability test
The expandable vaginal suppositories of examples 1 to 6 and comparative examples 1 to 6 were left under a constant condition of 25 ℃. + -. 2 ℃ and 65%. + -. 5% relative humidity for 6 months, and the properties of the expandable vaginal suppositories, the labeled amount (%) of recombinant human interferon α 1b 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 α 1b in vaginal dilation tampons
The expandable vaginal suppository of examples 1-6 is placed under the constant conditions of 25 ℃ +/-2 ℃ and 65% +/-5% relative humidity for 6 months, the color is unchanged, the surface is smooth, the characters such as rupture and long spots are not changed, the marked amount is not obviously changed, and the fusion time limit is not basically prolonged.
Compared with the example 1, the vaginal dilation suppository of the comparative examples 1-2 is cracked, has rough surface and bacterial plaque, changes into yellow brown, obviously reduces the content of the recombinant human interferon α 1b, obviously prolongs the melting time limit, and the vaginal dilation suppository of the comparative examples 3-6 has reduced marked amount and prolonged melting time limit although the characters are not changed.
Test for duration of drug action
The results of the drug release time of the expandable vaginal suppositories of examples 1 to 6 and comparative examples 1 to 2 are shown in Table 4.
TABLE 4 drug Release time for vaginal dilation suppository
| Numbering | Release time (h) |
| Example 1 | 24 |
| Example 2 | 20 |
| Example 3 | 20 |
| Example 4 | 18 |
| Example 5 | 18 |
| Example 6 | 20 |
| Comparative example 1 | 4 |
| Comparative example 2 | 10 |
The drug effect of the vaginal dilation suppository of examples 1-6 can last for more than 12 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 example 1-2 is not coated with high molecular polymer, and the recombinant human interferon can be quickly absorbed by the affected part, so that the drug effect time is short and the toxicity is high.
Gardnerella resistance test
The in vitro antibacterial drug sensitivity test refers to the in vitro test of the bacteriostatic or bactericidal capacity of the drug, the invention adopts the Oxford cup method to judge the inhibition effect of the test solution of the examples and the comparative examples on Gardner bacteria, and the configuration of the test solution is mixed according to the proportion of the recombinant human interferon α 1b and the traditional Chinese medicine composition described in the examples 1-6 and the comparative examples 3-4.
The method comprises the following specific steps: under the aseptic condition, 0.1mL of Gardner bacterium suspension is sucked and evenly coated on a plate culture medium, and 3 aseptic oxford cups are stably placed in each culture medium at a medium distance; 0.1mL of the test solution was added dropwise to the Oxford cup, and the mixture was placed in 5% CO2Culturing for 48h at 37 ℃ in an incubator, removing the Oxford cup, accurately measuring the diameter of each inhibition zone by using a vernier caliper, and comparing the inhibition effects.
The antibacterial sensitivity of the medicine is judged according to the diameter of the bacteriostatic circle, and the judgment standard refers to table 5.
TABLE 5 drug sensitivity test criteria
| Diameter of bacteriostatic circle (mm) | Sensitivity of the device |
| Greater than 20 | Extreme sensitivity |
| 15-20 | High sensitivity |
| 10-14 | Mianmin |
| 1-10 | Hyposensitivity |
| 0 | Is not sensitive to |
The results are shown in Table 6.
TABLE 6 experimental results against Gardnerella
| Numbering | Bacterial liquid concentration (cfu/g) | Diameter of bacteriostatic circle (mm) | Sensitivity of the device |
| Example 1 | 105-106 | 27.20 | Extreme sensitivity |
| Example 2 | 105-106 | 26.72 | Extreme sensitivity |
| Example 3 | 105-106 | 25.26 | Extreme sensitivity |
| Example 4 | 105-106 | 25.17 | Extreme sensitivity |
| Example 5 | 105-106 | 24.88 | Extreme sensitivity |
| Example 6 | 105-106 | 24.26 | Extreme sensitivity |
| Comparative example 3 | 105-106 | 14.13 | Mianmin |
| Comparative example 4 | 105-106 | 11.36 | Mianmin |
As can be seen from examples 1-6 and comparative examples 3-4, interferon has inhibitory action on Gardner's bacillus, wherein the inhibitory action of recombinant human interferon α 1b on Gardner's bacillus is better than that of recombinant human interferon α 2a and recombinant human interferon α 2b on Gardner's bacillus, from examples 1-6 comparison, the Chinese medicinal composition of radix Arnebiae extract, Viola yedoensis extract, Fluoritum extract and placenta hominis extract has significant synergistic action on recombinant human interferon α 1b, compared with example 6, examples 1-5 combine recombinant human interferon α 1b and Chinese medicinal composition, synergistic each other, the inhibitory action of recombinant human interferon α 1b on Gardner's bacillus is significantly enhanced, and when recombinant human interferon α 1b is 0.1 part, radix Arnebiae extract is 15 parts, Viola yedoensis extract is 8 parts, Fluoritum extract is 5 parts, placenta hominis extract is 5 parts, the best synergistic action of recombinant human interferon α 1b and the most significant inhibitory action on Gardner's bacillus.
In conclusion, the swelling value of the vaginal swelling suppository is greater than 1.5, 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 α 1b are improved, the release speed and the release time of active ingredients are controlled, the side effect of the recombinant human interferon α 1b is reduced, and the curative effect of the recombinant human interferon α 1b is remarkably improved under the coordination of the traditional Chinese medicine composition consisting of the lithospermum extract, the viola yedoensis extract, the amethyst extract and the human placenta 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 (13)
1. The vaginal expansion suppository is characterized by comprising 0.01-1.0 part of recombinant human interferon α 1b, 10-50 parts of high molecular polymer, 50-200 parts of matrix, 500 parts of expansion carrier, 5-20 parts of lithospermum extract, 5-10 parts of Chinese violet extract, 1-10 parts of amethyst extract and 1-10 parts of human placenta extract in parts by weight;
the recombinant human interferon α 1b, a Chinese medicinal composition lithospermum extract, a Chinese violet extract, a amethyst extract and a human placenta extract are fully mixed and sprayed on the surface of the matrix plug in a spray form;
the high molecular polymer is coated on the outer layer of the vaginal expansion suppository.
2. The expandable vaginal suppository as claimed in claim 1, wherein the expandable vaginal suppository comprises, by weight, 0.05-0.5 part of recombinant human interferon α 1b, 10-18 parts of lithospermum erythrorhizon extract, 5-9 parts of Chinese violet herb extract, 2-8 parts of amethyst extract, 2-8 parts of human placenta extract, 30-50 parts of high molecular polymer, 80-150 parts of matrix and 150 parts of expansion carrier.
3. The expandable vaginal suppository as claimed in claim 2, which comprises, by weight, 0.1 part of recombinant human interferon α 1b, 15 parts of lithospermum extract, 8 parts of Chinese violet herb extract, 5 parts of amethyst extract, 5 parts of human placenta extract, 35 parts of high molecular polymer, 120 parts of matrix and 300 parts of expandable carrier.
4. 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.
5. The expandable vaginal suppository of claim 4, wherein the high molecular weight polymer is a polylactic-co-glycolic acid.
6. The expandable vaginal suppository of claim 1, wherein the matrix comprises any one or more of synthetic fatty acid esters, natural fatty acid esters, lipid matrices or colloidal compounds.
7. The expandable vaginal suppository of claim 6, wherein the matrix is a combination of synthetic fatty acid esters and colloidal compounds.
8. The expandable vaginal suppository of claim 7, wherein the weight ratio of the synthetic fatty acid ester to the colloidal compound is 5: 1.
9. The expandable vaginal suppository of claim 1, wherein the expandable carrier comprises any one of a tampon, a nonwoven fabric or an elastic fiber.
10. The expandable vaginal suppository of claim 9 wherein the expandable carrier is a tampon.
11. A method of preparing a vaginal expansion plug as claimed in any one of claims 1 to 10 comprising the steps of:
(1) putting the matrix in a water bath for heating and melting to obtain a melt;
(2) pouring the melt obtained in the step (1) into a plug mold, inserting an expansion carrier, and cooling and shaping to obtain a matrix plug core;
(3) fully mixing the recombinant human interferon α 1b and the traditional Chinese medicine composition, spraying the mixture on the surface of the matrix suppository core obtained in the step (2) in a spraying mode, and cooling to obtain the suppository;
(4) and (4) adding the suppository in the step (3) into a high molecular polymer, performing ultrasonic treatment, and drying to obtain the vaginal expansion suppository.
12. The method of claim 11, wherein the temperature of the water bath of step (1) is 60-70 ℃.
13. The method of claim 11, wherein the temperature of the temperature reduction in step (3) is 35-45 ℃.
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