CN107583036A - A kind of recombinant human interferon alpha 1 b vaginal expansion plug and preparation method thereof - Google Patents
A kind of recombinant human interferon alpha 1 b vaginal expansion plug and preparation method thereof Download PDFInfo
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- CN107583036A CN107583036A CN201711059492.1A CN201711059492A CN107583036A CN 107583036 A CN107583036 A CN 107583036A CN 201711059492 A CN201711059492 A CN 201711059492A CN 107583036 A CN107583036 A CN 107583036A
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- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a kind of recombinant human interferon alpha 1 b vaginal expansion plug and preparation method thereof, the vaginal expansion plug includes in parts by weight：100 500 parts of 0.01 1.0 parts of recombinant human interferon alpha 1 b, 10 50 parts of high molecular polymer, 50 200 parts of matrix and expandable carrier.The vaginal expansion plug of the present invention uses the recombinant human interferon alpha 1 b suitable for Chinese's constitution as main active, it is evident in efficacy, and in its external sheath high molecular polymer, control rate of release and the action time of active component, reduce and be administered daily number, recombinant human interferon alpha 1 b is preferably absorbed by the body, is distributed and be metabolized, toxic side effect is small.
Description
Technical field
The invention belongs to pessary field, is related to a kind of vaginal expansion plug and preparation method thereof, and in particular to Yi Zhongchong
Group human interferon alpha 1 b vaginal expansion plug and preparation method thereof.
Background technology
Recombinant human interferon alpha 1 b is a kind of high activity multi-functional as caused by China's Healthy human leukocytes and lymphocyte
Albumen is induced, there is significant broad-spectrum disease resistance toxic action and immunoloregulation function, there is the effect of notable, side effect to vaginitis
It is small, suitable for Chinese's constitution.At present, the formulation of recombinant human interferon alpha 1 b is mainly tablet and suppository, but recombined human is disturbed
Plain α 1b meet light and wet easily decomposition, and the development difficulty of novel form is larger, has had a strong impact on the extensive use of recombinant human interferon alpha 1 b.
The shortcomings that tablet recombinant human interferon alpha 2 is dissolution difficulty, and effect is faint and poor to the adaptability of vagina, to suffering from
Person's body can cause potential injury；And suppository recombinant human interferon alpha 2 is present that disintegration rate is slow, assimilation effect is poor, inconvenient for use, dirty
The shortcomings of contaminating clothing, drug effect is influenceed by patient body position, and the affected part such as posterior fornix facies ventralis is difficult to touch medicine.
The B of CN 103751098 disclose recombinant human interferon alpha-2 vaginal expansion plug and preparation method thereof and detection method,
The expansible plug adds the а of recombinant human interferon-alpha 2 protective agent, not only increases the а of recombinant human interferon-alpha 2 stability, and
Improve the bioavilability of medicine.However, the а of recombinant human interferon-alpha 2 is coated on the outer layer of expansible plug, contact fast behind affected part
Speed absorbs, and blood concentration rises and falls greatly, and efficacy time is short, and effect is poor, has certain toxic side effect.
The A of CN 105012938 disclose recombinant human interferon alpha 2 b vaginal expansion plug and preparation method thereof and detection method,
The expansible plug adds the mixture of Herba Corydalis Bungeanae extract, Kaempferol -3-O- β-D sophoras flower glycosides and lauryl sodium sulfate, and
The magnetic microsphere that the cross-linking agent of Armco magnetic iron cross-linked esterification cassava modified starch and chitin-methylcellulose is formed, with recombined human
Interferon alpha 2 b Synergistic, the effect of improving suppository.However, recombinant human interferon alpha 2 b and its mixing point of Synergistic composition
It is distributed in matrix, forms drug containing matrix, active component reduces with human contact's area, can not be fully absorbed, cause by human body
A certain degree of waste, the optimum therapeuticing effect of suppository can not be played.
Therefore it provides a kind of recombinant human interferon alpha 1 b vaginal expansion plug and preparation method thereof, make expansible plug to vaginitis not
Only there is significant therapeutic effect, and curative effect is lasting, and toxic side effect is small, significant to pessary field.
The content of the invention
The defects of existing for prior art, the invention provides a kind of recombinant human interferon alpha 1 b vaginal expansion plug and its
Preparation method, the vaginal expansion plug use recombinant human interferon alpha 1 b suitable for Chinese's constitution as main active,
And in its external sheath high molecular polymer, evident in efficacy, toxic side effect is small.
In a first aspect, the invention provides a kind of vaginal expansion plug, the vaginal expansion plug includes in parts by weight：Restructuring
Human interferon alpha 1 b 0.01-1.0 parts, high molecular polymer 10-50 parts, matrix 50-200 parts and expandable carrier 100-500 parts.
Vaginal expansion plug provided by the invention uses recombinant human interferon alpha 1 b as main active, suitable for China
People's constitution, in its external sheath high molecular polymer, rate of release and the action time of active component are controlled, is reduced daily
Administration number of times so that recombinant human interferon alpha 1 b can preferably be absorbed by the body, is distributed and be metabolized, and give full play to it and significantly treat
Effect.
Preferably, the parts by weight of the recombinant human interferon alpha 1 b are 0.01-1.0 parts, such as can be 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, preferably 0.95 part or 1.0 parts, 0.05-0.5 parts, enter one
Step is preferably 0.1 part.
Preferably, the parts by weight of the high molecular polymer are 10-50 parts, for example, can be 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, it is preferably
30-50 parts, more preferably 35 parts.
Preferably, the parts by weight of the matrix are 50-200 parts, for example, can be 50 parts, 60 parts, 70 parts, 80 parts, 90
Part, 100 parts, 110 parts, 120 parts, 130 parts, 140 parts, 150 parts, 160 parts, 170 parts, 180 parts, 190 parts or 200 parts, be preferably
80-150 parts, more preferably 120 parts.
Preferably, the parts by weight of the expandable carrier are 100-500 parts, for example, can be 100 parts, 120 parts, 150 parts,
180 parts, 200 parts, 220 parts, 250 parts, 280 parts, 300 parts, 320 parts, 350 parts, 380 parts, 400 parts, 420 parts, 450 parts, 480 parts
Or 500 parts, preferably 150-400 parts, more preferably 300 parts.
Preferably, the vaginal expansion plug also includes Chinese medicine composition.
Chinese medical extract in the present invention has with recombinant human interferon alpha 1 b in terms of vaginitis is treated significantly cooperates with work
With, after adding Chinese medicine composition, recombinant human interferon alpha 1 b significantly improves to the therapeutic effect of vagina inflammation, therefore same
Etc. under therapeutic effect, it is possible to reduce the dosage of interferon, so as to reduce the side effect for the treatment of cost and interferon.
Preferably, the Chinese medicine composition includes in parts by weight：Radix Arnebiae extract 5-20 parts, Herba Violae extract 5-
10 parts, amethyst extract 1-10 parts and Placenta Hominis extract 1-10 parts.
Preferably, the parts by weight of the Radix Arnebiae extract are 5-20 parts, for example, can be 5 parts, 6 parts, 7 parts, 8 parts, 9
Part, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, preferably 19 parts or 20 parts, 10-18 parts, enter one
Step is preferably 15 parts.
Preferably, the parts by weight of the Herba Violae extract are 5-10 parts, for example, can be 5 parts, 6 parts, 7 parts, 8
Part, more preferably 9 parts or 10 parts, preferably 5-9 parts, 8 parts.
Preferably, the parts by weight of the amethyst extract are 1-10 parts, for example, can be 1 part, 2 parts, 3 parts, 4 parts, 5
Part, 6 parts, 7 parts, 8 parts, more preferably 9 parts or 10 parts, preferably 2-8 parts, 5 parts.
Preferably, the parts by weight of the Placenta Hominis extract are 1-10 parts, for example, can be 1 part, 2 parts, 3 parts, 4 parts, 5
Part, 6 parts, 7 parts, 8 parts, more preferably 9 parts or 10 parts, preferably 2-8 parts, 5 parts.
Preferably, the vaginal expansion plug includes in parts by weight：Recombinant human interferon alpha 1 b 0.05-0.5 parts, Asian puccoon carry
Take thing 10-18 parts, Herba Violae extract 5-9 parts, amethyst extract 2-8 parts, Placenta Hominis extract 2-8 parts, polyphosphazene polymer
Compound 30-50 parts, matrix 80-150 parts and expandable carrier 150-400 parts.
Preferably, the vaginal expansion plug includes in parts by weight：0.1 part of recombinant human interferon alpha 1 b, Radix Arnebiae extract
15 parts, 8 parts of Herba Violae extract, 5 parts of amethyst extract, 5 parts of Placenta Hominis extract, 35 parts of high molecular polymer, matrix
120 parts and 300 parts of expandable carrier.
Preferably, the high molecular polymer includes PLA, pla-pcl, Poly(D,L-lactide-co-glycolide or poly-
In urethane any one or at least two combination, such as can be the combination of PLA and pla-pcl, PLA and poly-
The combination of the combination of poly lactic coglycolic acid, PLA and polyurethane, pla-pcl and poly lactic-co-glycolic acid copolymerization
The combination of the combination of thing, pla-pcl and polyurethane, or the combination of Poly(D,L-lactide-co-glycolide and polyurethane, it is preferably
Poly(D,L-lactide-co-glycolide.
Preferably, the matrix is included in Acrawax, natural acid ester, lipoidis matrix or colloidal compound
Any one or at least two combination, such as can be the combination of Acrawax and natural acid ester, synthetic fat
The combination of the combination of fat acid esters and lipoidis matrix, Acrawax and colloidal compound, natural acid ester and lipoidis
The combination of the combination of matrix, natural acid ester and colloidal compound, or the combination of lipoidis matrix and colloidal compound, preferably
For the combination of Acrawax and colloidal compound.
Preferably, the weight ratio of the Acrawax and colloidal compound is (1-10):1, such as can be 1:1、
2:1、3:1、4:1、5:1、6:1、7:1、8:1、9:1 or 10:1, be preferably (2-10):1, more preferably 5:1.
Preferably, the expandable carrier includes any one in sliver, non-woven fabrics or elastomer or at least two
The group of combination, such as can be the combination of sliver and non-woven fabrics, the combination of sliver and elastomer, non-woven fabrics and elastomer
Conjunction, or the combination of sliver, non-woven fabrics and elastomer, preferably sliver.
Second aspect, the invention provides a kind of method for preparing vaginal expansion plug as described in relation to the first aspect, including it is as follows
Step：
(1) matrix is placed in heat in water-bath and melted, obtain fused mass；
(2) step (1) described fused mass is poured into bolt mould, inserts expandable carrier, cooling and shaping, matrix bolt core is made；
(3) after being sufficiently mixed recombinant human interferon alpha 1 b and Chinese medicine composition, with Sprayable spray attachment in step (2) institute
The surface of matrix bolt core is stated, suppository is made after cooling；
(4) step (3) described suppository is added to high molecular polymer and carries out ultrasound, the vagina expansion is made after drying
Bolt.
Preferably, the temperature of step (1) described water-bath is 60-70 DEG C, for example, can be 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) described cooling is 35-45 DEG C, for example, can be 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 prior art, the present invention has the advantages that：
(1) swell value of vaginal expansion plug is more than 1.5, and weight differential is less than ± 10%, and wherein axial expansion value is up to
1.92, it is radially expanded value and is up to 1.91, weight differential minimum ± 0.02%；
(2) vaginal expansion plug external sheath has high molecular polymer, improves the activity and stability of vaginal expansion plug,
Placed 2 years at 37 DEG C and remain in that 1.7 × 108IU/ pieces of external activity, 6 are placed in the environment that humidity is 65% ± 5%
Month, the labelled amount of recombinant human interferon alpha 1 b is up to 100.01%, and thaw time is stable in 25min；
(3) vaginal expansion plug external sheath has high molecular polymer, effectively controls the release speed of recombinant human interferon alpha 1 b
Degree and release time so that the duration of efficacy of vaginal expansion plug is for up to 24 hours；
(4) in the Chinese medicine group of Radix Arnebiae extract, Herba Violae extract, amethyst extract and Placenta Hominis extract composition
It is significantly improved under the cooperation of compound, the effect of recombinant human interferon alpha 1 b.
Embodiment
For the present invention technological means and its effect taken is expanded on further, the present invention is made with reference to embodiments into
Illustrate to one step.It is understood that embodiment described herein is used only for explaining the present invention, rather than to this hair
Bright restriction.
In the examples where no specific technique or condition is specified, according to the technology or condition described by document in the art,
Or carried out according to product description.Agents useful for same or the unreceipted production firm person of instrument, be can be by regular channel commercially available from
The conventional products of acquisition.
Embodiment 1
In the present embodiment, vaginal expansion plug includes in parts by weight：0.1 part of recombinant human interferon alpha 1 b, Asian puccoon extraction
15 parts of thing, 8 parts of Herba Violae extract, 5 parts of amethyst extract, 5 parts of Placenta Hominis extract, poly lactic-co-glycolic acid copolymerization
300 parts of 120 parts of the mixture of 35 parts of thing, Acrawax and colloidal compound and sliver.
Preparation method is as follows：
(1) it is 5 by weight by Acrawax and colloidal compound:After 1 mixing, it is placed in heat in 65 DEG C of water-baths and melts
Melt, obtain fused mass；
(2) step (1) described fused mass is poured into bolt mould, inserts sliver, cooling and shaping, matrix bolt core is made；
(3) after being sufficiently mixed recombinant human interferon alpha 1 b and Chinese medicine composition, with Sprayable spray attachment in step (2) institute
The surface of matrix bolt core is stated, suppository is made after cooling to 40 DEG C；
(4) step (3) described suppository is added in Poly(D,L-lactide-co-glycolide and carries out ultrasound, be made after drying
The vaginal expansion plug.
Embodiment 2
In the present embodiment, vaginal expansion plug includes in parts by weight：0.05 part of recombinant human interferon alpha 1 b, Asian puccoon extraction
18 parts of thing, 5 parts of Herba Violae extract, 8 parts of amethyst extract, 2 parts of Placenta Hominis extract, 50 parts of PLA, synthctic fat
400 parts of 80 parts of the mixture and non-woven fabrics of acid esters and natural acid ester.
Preparation method is as follows：
(1) it is 6 by weight by Acrawax and natural acid ester:After 1 mixing, it is placed in 64 DEG C of water-baths and heats
Melting, obtains fused mass；
(2) step (1) described fused mass is poured into bolt mould, inserts non-woven fabrics, cooling and shaping, matrix bolt core is made；
(3) after being sufficiently mixed recombinant human interferon alpha 1 b and Chinese medicine composition, with Sprayable spray attachment in step (2) institute
The surface of matrix bolt core is stated, suppository is made after cooling to 41 DEG C；
(4) step (3) described suppository is added in PLA and carries out ultrasound, the vaginal expansion plug is made after drying.
Embodiment 3
In the present embodiment, vaginal expansion plug includes in parts by weight：0.5 part of recombinant human interferon alpha 1 b, Asian puccoon extraction
10 parts of thing, 9 parts of Herba Violae extract, 2 parts of amethyst extract, 8 parts of Placenta Hominis extract, 30 parts of pla-pcl, synthetic fat
Fat acid esters and 150 parts of 150 parts of the mixture of lipoidis matrix and elastomer.
Preparation method is as follows：
(1) it is 2 by weight by Acrawax and lipoidis matrix:After 1 mixing, it is placed in heat in 68 DEG C of water-baths and melts
Melt, obtain fused mass；
(2) step (1) described fused mass is poured into bolt mould, inserts elastomer, cooling and shaping, matrix bolt core is made；
(3) after being sufficiently mixed recombinant human interferon alpha 1 b and Chinese medicine composition, with Sprayable spray attachment in step (2) institute
The surface of matrix bolt core is stated, suppository is made after cooling to 37 DEG C；
(4) step (3) described suppository is added in pla-pcl and carries out ultrasound, the vagina expansion is made after drying
Bolt.
Embodiment 4
In the present embodiment, vaginal expansion plug includes in parts by weight：0.01 part of recombinant human interferon alpha 1 b, Asian puccoon extraction
20 parts of thing, 5 parts of Herba Violae extract, 10 parts of amethyst extract, 1 part of Placenta Hominis extract, 50 parts of polyurethane, natural fat
Acid esters and 500 parts of 50 parts of the mixture of lipoidis matrix and sliver.
Preparation method is as follows：
(1) it is 10 by weight by natural acid ester and lipoidis matrix:After 1 mixing, it is placed in 60 DEG C of water-baths and heats
Melting, obtains fused mass；
(2) step (1) described fused mass is poured into bolt mould, inserts sliver, cooling and shaping, matrix bolt core is made；
(3) after being sufficiently mixed recombinant human interferon alpha 1 b and Chinese medicine composition, with Sprayable spray attachment in step (2) institute
The surface of matrix bolt core is stated, suppository is made after cooling to 45 DEG C；
(4) step (3) described suppository is added in polyurethane and carries out ultrasound, the vaginal expansion plug is made after drying.
Embodiment 5
In the present embodiment, vaginal expansion plug includes in parts by weight：1 part of recombinant human interferon alpha 1 b, Radix Arnebiae extract 5
Part, 10 parts of Herba Violae extract, 1 part of amethyst extract, 10 parts of Placenta Hominis extract, PLA-pla-pcl copolymer
10 parts, 100 parts of 200 parts of the mixture and non-woven fabrics of natural acid ester and colloidal compound.
Preparation method is as follows：
(1) it is 1 by weight by natural acid ester and colloidal compound:After 1 mixing, it is placed in heat in 70 DEG C of water-baths and melts
Melt, obtain fused mass；
(2) step (1) described fused mass is poured into bolt mould, inserts non-woven fabrics, cooling and shaping, matrix bolt core is made；
(3) after being sufficiently mixed recombinant human interferon alpha 1 b and Chinese medicine composition, with Sprayable spray attachment in step (2) institute
The surface of matrix bolt core is stated, suppository is made after cooling to 35 DEG C；
(4) step (3) described suppository is added in PLA-pla-pcl copolymer and carries out ultrasound, be made after drying
The vaginal expansion plug.
Embodiment 6
Compared with Example 1, in the present embodiment, except not including Chinese traditional medicine composition beyond the region of objective existence, vaginal expansion plug is in parts by weight
Including：0.1 part of recombinant human interferon alpha 1 b, 35 parts of Poly(D,L-lactide-co-glycolide, Acrawax and colloidal compound
300 parts of 120 parts of mixture and sliver.Other preparation process are same as Example 1.
Comparative example 1
Compared with Example 1, in the present embodiment, in addition to not including Poly(D,L-lactide-co-glycolide, vaginal expansion plug
Include in parts by weight：0.1 part of recombinant human interferon alpha 1 b, 15 parts of Radix Arnebiae extract, 8 parts of Herba Violae extract, amethyst
5 parts of extract, 5 parts of Placenta Hominis extract, 300 parts of 120 parts of the mixture and sliver of Acrawax and colloidal compound.Its
His preparation process is same as Example 1.
Comparative example 2
Compared with Example 1, in the present embodiment, the preparation method of vaginal expansion plug comprises the following steps：
(1) it is 5 by weight by Acrawax and colloidal compound:After 1 mixing, it is placed in heat in 65 DEG C of water-baths and melts
Melt, obtain fused mass；
(2) Chinese medicine composition is added in step (1) described fused mass, is cooled to 40 DEG C, mixture is made；
(3) recombinant human interferon alpha 1 b is added in step (2) described mixture, drug containing matrix is made；
(4) step (3) the drug containing matrix is poured into bolt mould, inserts sliver, cooling and shaping, suppository is made；
(5) step (4) described suppository is added in Poly(D,L-lactide-co-glycolide and carries out ultrasound, be made after drying
The vaginal expansion plug.
Comparative example 3
Compared with Example 1, in the present embodiment, vaginal expansion plug includes in parts by weight：Recombinant human interferon alpha-2
0.1 part, 15 parts of Radix Arnebiae extract, 8 parts of Herba Violae extract, 5 parts of amethyst extract, 5 parts of Placenta Hominis extract, poly- breast
300 parts of 120 parts of the mixture of 35 parts of acid-co-glycolic acid, Acrawax and colloidal compound and sliver.Other systems
Standby process is same as Example 1.
Comparative example 4
Compared with Example 1, in the present embodiment, vaginal expansion plug includes in parts by weight：Recombinant human interferon alpha 2 b
0.1 part, 15 parts of Radix Arnebiae extract, 8 parts of Herba Violae extract, 5 parts of amethyst extract, 5 parts of Placenta Hominis extract, poly- breast
300 parts of 120 parts of the mixture of 35 parts of acid-co-glycolic acid, Acrawax and colloidal compound and sliver.Other systems
Standby process is same as Example 1.
Comparative example 5
Compared with Example 1, in the present embodiment, vaginal expansion plug includes in parts by weight：Recombinant human interferon alpha 1 b
0.005 part, 25 parts of Radix Arnebiae extract, 1 part of Herba Violae extract, 15 parts of amethyst extract, 0.5 part of Placenta Hominis extract,
550 parts of 30 parts of the mixture of 60 parts of Poly(D,L-lactide-co-glycolide, Acrawax and colloidal compound and sliver.Its
His preparation process is same as Example 1.
Comparative example 6
Compared with Example 1, in the present embodiment, vaginal expansion plug includes in parts by weight：Recombinant human interferon alpha 1 b 5
Part, 1 part of Radix Arnebiae extract, 15 parts of Herba Violae extract, 0.5 part of amethyst extract, 15 parts of Placenta Hominis extract, poly- breast
80 parts of 220 parts of the mixture of 5 parts of acid-co-glycolic acid, Acrawax and colloidal compound and sliver.Other are prepared
Process is same as Example 1.
Swell value and weight differential determination experiment
Axial expansion value is carried out to embodiment 1-6 vaginal expansion plug, is radially expanded the measure of value and weight differential.
(1) axial expansion values determination method
If 1) choose a little or do along the radial direction of the vaginal expansion plug end face, the initial length of the expandable carrier is determined
H is spent, then rolls different angle measurement several times, obtains initial average length Hi；
2) vaginal expansion plug melt become time limit detection after, determination step 1) expansion of expandable carrier at selected location
Length h, then roll different angle measurement several times, the average length hi after being expanded；
3) according to pi=hi/Hi, the axial expansion value of the vaginal expansion plug is calculated.
(2) it is radially expanded values determination method
If 1) choose a little or do along the axial direction of the vaginal expansion plug end face, the initial straight of the expandable carrier is determined
Footpath R, then roll different angle measurement several times, obtain initial mean diameter Ri；
2) vaginal expansion plug melt become time limit detection after, determination step 1 ') expandable carrier is swollen at selected location
Swollen length r, then roll different angle measurement several times, the average length ri after being expanded；
3) according to Pi=ri/Ri, the vaginal expansion plug is calculated is radially expanded value.
(3) weight differential assay method
1) the initial weight M of vaginal expansion plug is weighed；
2) after scraping high molecular polymer, medicament and matrix, expandable carrier is placed in 20-90 DEG C of organic solvent, taken out,
In 50-150 DEG C of dry 1-10h, weight m is weighed；
3) according to X=M-m, the gross weight X of the high molecular polymer, medicament and matrix is calculated.
As a result it is as shown in table 1.
The swell value and weight differential of the vaginal expansion plug of table 1
| Numbering | Axial expansion value | It is radially expanded value | Weight differential |
| Embodiment 1 | 1.92 | 1.91 | ± 0.02% |
| Embodiment 2 | 1.88 | 1.87 | ± 0.13% |
| Embodiment 3 | 1.87 | 1.88 | ± 0.12% |
| Embodiment 4 | 1.82 | 1.84 | ± 0.27% |
| Embodiment 5 | 1.82 | 1.82 | ± 0.25% |
| Embodiment 6 | 1.79 | 1.80 | ± 0.28% |
The axial/radial swell value of embodiment 1-6 vaginal expansion plug is all higher than 1.5, and weight differential is respectively less than ± 10%,
As a result it is qualified.
External activity is tested
Using MTT colorimetric methods, embodiment 1-6 and comparative example 1-6 vaginal expansion plug is determined at 4 DEG C, 25 DEG C and 37 DEG C
External activity after placing 2 years, initial potency are 5.2 × 108IU/ pieces, as a result as shown in table 2.
The external activity of recombinant human interferon alpha 1 b in the vaginal expansion plug of table 2
| Numbering | 4℃ | 25℃ | 37℃ |
| Embodiment 1 | 5.1×108 | 3.6×108 | 1.7×108 |
| Embodiment 2 | 4.9×108 | 3.1×108 | 8.4×107 |
| Embodiment 3 | 4.9×108 | 2.9×108 | 8.5×107 |
| Embodiment 4 | 4.7×108 | 2.2×108 | 7.8×107 |
| Embodiment 5 | 4.8×108 | 2.0×108 | 7.8×107 |
| Embodiment 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 |
Embodiment 1-6 vaginal expansion plug is placed 2 years at 4 DEG C, and the external activity of vaginal expansion plug does not become substantially
Change, placed 2 years at 25 DEG C and 37 DEG C, the external activity of vaginal expansion plug only slightly reduces, and the vagina of wherein embodiment 1 is swollen
Swollen bolt is placed 2 years at 4 DEG C, 25 DEG C and 37 DEG C and is maintained to higher activity.Therefore, vaginal expansion plug external sheath
High molecular polymer the activity of recombinant human interferon alpha 1 b can be effectively ensured, to recombinant human interferon alpha 1 b and Chinese medicine composition
With protective effect.
Compared with Example 1, comparative example 1-2 vaginal expansion plug is placed 2 years its activity at 4 DEG C and is declined slightly, 37
The basic disappearance of its activity in 2 years is placed at DEG C, can not be used；The activity of comparative example 3-6 vaginal expansion plug is not as good as embodiment 1-
6。
Stability experiment
By embodiment 1-6 and comparative example 1-6 vaginal expansion plug temperature be 25 DEG C ± 2 DEG C, relative humidity be 65% ±
Placed 6 months under 5% controlled condition, by the regulation in Chinese Pharmacopoeia, determine character, the recombinant human interferon alpha 2 of vaginal expansion plug
α 1b labelled amount (%) and melt become the time limit, as a result as shown in table 3.
The stability of recombinant human interferon alpha 1 b in the vaginal expansion plug of table 3
Embodiment 1-6 vaginal expansion plug is in the controlled condition that temperature is 25 DEG C ± 2 DEG C, relative humidity is 65% ± 5%
Lower to place 6 months, color does not change, and surface is smooth, does not occur the change of the characters such as rupture, long spot, and labelled amount does not occur substantially
Change, melt become the time limit do not extend substantially.Therefore, the high molecular polymer of vaginal expansion plug external sheath can be effectively ensured
The stability of recombinant human interferon alpha 1 b, there is protective effect to recombinant human interferon alpha 1 b and Chinese medicine composition.
Compared with Example 1, comparative example 1-2 vaginal expansion plug ruptures, and rough surface has bacterial plaque, and color is changed into yellow
Brown, the content of recombinant human interferon alpha 1 b significantly reduce, melt become the time limit be obviously prolonged；Comparative example 3-6 vaginal expansion plug although
The change of character does not occur, but labelled amount decreases, melt and become the time limit and extended.
Duration of efficacy determination experiment
The pharmaceutical release time result of embodiment 1-6 and comparative example 1-2 vaginal expansion plug is as shown in table 4.
The pharmaceutical release time of the vaginal expansion plug of table 4
| Numbering | Release time (h) |
| Embodiment 1 | 24 |
| Embodiment 2 | 20 |
| Embodiment 3 | 20 |
| Embodiment 4 | 18 |
| Embodiment 5 | 18 |
| Embodiment 6 | 20 |
| Comparative example 1 | 4 |
| Comparative example 2 | 10 |
Sustainable more than 12 hours of the drug effect of embodiment 1-6 vaginal expansion plug, wherein, the vaginal expansion plug of embodiment 1
Duration of efficacy it is most long, up to 24 hours；Compared with Example 1, the uncoated polyphosphazene polymer of comparative example 1-2 vaginal expansion plug
Compound, recombinant human interferon alpha 2 can be absorbed rapidly by affected part, and efficacy time is short, and toxicity is big.
Anti- Gardnerella experiment
The experiment of in-vitro antibacterial Drug sensitivity refers to determine the ability that medicine is antibacterial or sterilizes in vitro, of the invention to use
Odontothrips loti, judge inhibitory action of the experimental liquid to Gardnerella of embodiment and comparative example.The configuration of experimental liquid is according to implementation
The ratio mixing of recombinant human interferon alpha 1 b and Chinese medicine composition described in example 1-6 and comparative example 3-4.
Comprise the following steps that：Under aseptic condition, draw 0.1mL Gardnerella uniform suspensions and be coated on plating medium
On, each culture medium moderate distance steadily places 3 sterile Oxford cups；0.1mL experimental liquids are added dropwise respectively to Oxford cup, are placed in
5%CO237 DEG C of culture 48h, remove Oxford cup, with the diameter of each inhibition zone of slide measure accurate measuring, compare suppression in incubator
Bacterium effect.
The antimicrobial susceptibility of medicine, criterion reference table 5 are judged according to the size of antibacterial circle diameter.
The drug sensitivity assay criterion of table 5
| Antibacterial circle diameter (mm) | Susceptibility |
| More than 20 | It is extremely quick |
| 15-20 | Gao Min |
| 10-14 | In it is quick |
| 1-10 | Muting sensitive |
| 0 | It is unwise |
Experimental result is shown in Table 6.
The anti-Gardnerella experimental result of table 6
| Numbering | Bacterial concentration (cfu/g) | Antibacterial circle diameter (mm) | Susceptibility |
| Embodiment 1 | 105-106 | 27.20 | It is extremely quick |
| Embodiment 2 | 105-106 | 26.72 | It is extremely quick |
| Embodiment 3 | 105-106 | 25.26 | It is extremely quick |
| Embodiment 4 | 105-106 | 25.17 | It is extremely quick |
| Embodiment 5 | 105-106 | 24.88 | It is extremely quick |
| Embodiment 6 | 105-106 | 24.26 | It is extremely quick |
| Comparative example 3 | 105-106 | 14.13 | In it is quick |
| Comparative example 4 | 105-106 | 11.36 | In it is quick |
Interferon is inhibited to Gardnerella it can be seen from embodiment 1-6 and comparative example 3-4, wherein recombinating
Human interferon alpha 1 b is to the inhibitory action of Gardnerella better than recombinant human interferon alpha-2 and recombinant human interferon alpha 2 b to Gardnerella
Inhibitory action；Contrasted from embodiment 1-6, Radix Arnebiae extract, Herba Violae extract, amethyst extract and dried human placenta carry
Taking the Chinese medicine composition of thing has significant synergy to recombinant human interferon alpha 1 b, and compared with Example 6, embodiment 1-5 will
Recombinant human interferon alpha 1 b and Chinese medicine composition use in conjunction, mutually collaboration, suppression of the recombinant human interferon alpha 1 b to Gardnerella
Effect significantly increases, and when recombinant human interferon alpha 1 b is 0.1 part, Radix Arnebiae extract is 15 parts, Herba Violae extract is 8 parts,
When amethyst extract is 5 parts, Placenta Hominis extract is 5 parts, the synergy of recombinant human interferon alpha 1 b and Chinese medicine composition is most
It is excellent, it is most notable to the inhibitory action of Gardnerella.
In summary, the swell value of vaginal expansion plug of the invention is more than 1.5, and weight differential is less than ± 10%, outer layer bag
High molecular polymer is covered with, the external activity and stability of recombinant human interferon alpha 1 b is improved, controls the release of active ingredient
Speed and release time, the side effect of recombinant human interferon alpha 1 b is reduced, in Radix Arnebiae extract, Herba Violae extract, purple stone
Under the cooperation of the Chinese medicine composition of English extract and Placenta Hominis extract composition, obtain the effect of recombinant human interferon alpha 1 b significantly
Improve.
Applicant states that the present invention illustrates the method detailed of the present invention, but not office of the invention by above-described embodiment
It is limited to above-mentioned method detailed, that is, does not mean that the present invention has to rely on above-mentioned method detailed and could implemented.Art
Technical staff it will be clearly understood that any improvement in the present invention, equivalence replacement and auxiliary element to each raw material of product of the present invention
Addition, selection of concrete mode etc., within the scope of all falling within protection scope of the present invention and disclosing.
Claims (10)
1. a kind of vaginal expansion plug, it is characterised in that the vaginal expansion plug includes in parts by weight：Recombinant human interferon alpha 1 b
0.01-1.0 parts, high molecular polymer 10-50 parts, matrix 50-200 parts and expandable carrier 100-500 parts.
2. vaginal expansion plug according to claim 1, it is characterised in that the vaginal expansion plug also includes Chinese traditional medicine composition
Thing；
Preferably, the Chinese medicine composition includes in parts by weight：Radix Arnebiae extract 5-20 parts, Herba Violae extract 5-10
Part, amethyst extract 1-10 parts and Placenta Hominis extract 1-10 parts.
3. vaginal expansion plug according to claim 1 or 2, it is characterised in that the vaginal expansion plug is wrapped in parts by weight
Include：Recombinant human interferon alpha 1 b 0.05-0.5 parts, Radix Arnebiae extract 10-18 parts, Herba Violae extract 5-9 parts, amethyst carry
Take thing 2-8 parts, Placenta Hominis extract 2-8 parts, high molecular polymer 30-50 parts, matrix 80-150 parts and expandable carrier 150-400
Part.
4. according to the vaginal expansion plug described in claim any one of 1-3, it is characterised in that the vaginal expansion plug is by weight
Number includes：0.1 part of recombinant human interferon alpha 1 b, 15 parts of Radix Arnebiae extract, 8 parts of Herba Violae extract, amethyst extract 5
Part, 5 parts of Placenta Hominis extract, 35 parts of high molecular polymer, 120 parts of matrix and 300 parts of expandable carrier.
5. according to the vaginal expansion plug described in claim any one of 1-4, it is characterised in that the high molecular polymer includes poly-
In lactic acid, pla-pcl, Poly(D,L-lactide-co-glycolide or polyurethane any one or at least two combination, preferably
For Poly(D,L-lactide-co-glycolide.
6. according to the vaginal expansion plug described in claim any one of 1-5, it is characterised in that the matrix includes synthetic fatty acid
In ester, natural acid ester, lipoidis matrix or colloidal compound any one or at least two combination, it is preferably synthetic
The combination of fatty acid ester and colloidal compound；
Preferably, the weight ratio of the Acrawax and colloidal compound is (1-10):1, be preferably (2-10):1, enter one
Step is preferably 5:1.
7. according to the vaginal expansion plug described in claim any one of 1-6, it is characterised in that the expandable carrier include sliver,
In non-woven fabrics or elastomer any one or at least two combination, preferably sliver.
A kind of 8. method for preparing the vaginal expansion plug as described in claim any one of 1-7, it is characterised in that including following step
Suddenly：
(1) matrix is placed in heat in water-bath and melted, obtain fused mass；
(2) step (1) described fused mass is poured into bolt mould, inserts expandable carrier, cooling and shaping, matrix bolt core is made；
(3) after being sufficiently mixed recombinant human interferon alpha 1 b and Chinese medicine composition, with Sprayable spray attachment in step (2) base
The surface of matter bolt core, suppository is made after cooling；
(4) step (3) described suppository is added to high molecular polymer and carries out ultrasound, the vaginal expansion plug is made after drying.
9. according to the method for claim 8, it is characterised in that the temperature of step (1) described water-bath is 60-70 DEG C.
10. method according to claim 8 or claim 9, it is characterised in that the temperature of step (3) described cooling is 35-45 DEG C.
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