CN108310364A - A kind of amphotericin B vaginal expansion plug and preparation method thereof - Google Patents
A kind of amphotericin B vaginal expansion plug and preparation method thereof Download PDFInfo
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- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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Abstract
The present invention provides a kind of vaginal expansion plug and its preparation method and application, the expansible plug includes amphotericin B, nisin, matrix and expandable expandable carrier, and wherein expansible plug further includes lactobacillus.Vaginal expansion plug provided by the invention utilizes the active ingredients such as nisin and lactobacillus by combination, collaboration increases drug effect, improves vaginal flora environment, the ingredients such as matrix, emulsifier and sustained release agent are applied in combination, bioavilability is improved, bacterial vaginitis and colpomycosis are effectively treated.
Description
Technical field
The invention belongs to vaginal suppository field, it is related to a kind of vaginal expansion plug and preparation method thereof, and in particular to one kind two
Property mycin B vaginal expansion plugs and preparation method thereof.
Background technology
Vaginitis is common gynecological disease, seriously affects the Working Life of female normal.Colpomycosis is by white
Caused by color candida albicans, candida albicans is also known as candidiasis, is most common conditioned pathogen in fungi.Currently used administration
Dosage form includes the solutions such as suppository, tablet, ointment, gel-like semisolid preparation, lotion and spray.Suppository can be done directly on
Local drug concentration is improved in affected part, reduces whole body toxic side effect, is ideal administering mode.
It has been reported that the vaginal expansion plug of a variety for the treatment of candida albicans.CN103784390A discloses a kind of secnidazole vagina
Expansible plug and preparation method thereof and detection method, the expansible plug include secnidazole, matrix and expandable carrier.
It includes micro mist that CN103735493A, which discloses a kind of palmatine vaginal swelling bolt and preparation method thereof and detection method, the expansible plug,
The fibrauretine of change and substrate formed drug containing matrix and expandable carrier.But the suppository easily causes fungi drug resistance, to drop
Low curative effect.Amphotericin B belongs to a kind of polyenoid class spectrum antifungal antibiotic, with the sterol on fungal cell membrane phospholipid bilayer
Reciprocation occurs, cell membrane is caused to generate water-soluble duct, cell membrane penetration sexually revises so that cellular content is lost in and makes
At thalline death.In terms of clinical application, the antibody-resistant bacterium of amphotericin B is rare, compared with other common azole drugs, in vain
Color candida albicans is to the susceptibility higher of amphotericin B, and therefore, amphotericin B can effectively treat colpomycosis.
CN105616353A discloses a kind of temperature sensitive type amphotericin B nano gel foamable composition for vagina administration, by antifungal
Object amphotericin B, stabilizer phosphatide and Thermo-sensitive host material poloxamer composition.Existing report is by amphotericin B with effervesce
Piece is for treating colpomycosis, but effervescent tablet itself faces disintegration and transfinites, and sticks punching and the unstable problem of product, limits medicine
Effect plays, and seriously affects curative effect.
Therefore it provides a kind of curative effect is stablized, the amphotericin B suppository for being effective against colpomycosis is expanded in vagina
Bolt field is of great significance and broad prospect of application.
Invention content
In view of the deficiencies of the prior art and actual demand, the present invention provide a kind of amphotericin B vaginal expansion plug and its
Preparation method.
For this purpose, the present invention uses following technical scheme：
In a first aspect, the present invention provides a kind of amphotericin B vaginal expansion plug, the expansible plug includes amphotericin B, breast
Acid streptococci element, matrix and expandable expandable carrier, the parts by weight of each ingredient of expansible plug are：
It is a discovery of the invention that amphotericin B is synergistic with nisin, there is nisin itself sterilization to make
With being natural preservative, have no toxic side effect, while preventing suppository putrid and deteriorated, the sterilization of amphotericin B can be promoted
Effect, Synergistic antimicrobial improve the bioavilability of amphotericin B.
The amphotericin B is 10-25 parts, for example, can be 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 or 25 parts.
The nisin is 0.5-5 parts, for example, can be 0.5 part, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5
Part, 4 parts, 4.5 parts or 5 parts.
The matrix is 120-280 parts, for example, can be 120 parts, 125 parts, 130 parts, 140 parts, 150 parts, 160 parts, 170
Part, 180 parts, 190 parts, 200 parts, 210 parts, 220 parts, 230 parts, 240 parts, 250 parts, 260 parts, 270 parts, 275 parts or 280 parts.
The expandable carrier is 100-200 parts, for example, can be 100 parts, 105 parts, 110 parts, 120 parts, 130 parts, 140
Part, 150 parts, 160 parts, 170 parts, 180 parts, 190 parts, 195 parts or 200 parts.
Preferably, the expansible plug further includes lactobacillus.
In the present invention, the amphotericin B does not influence lactobacillus acidophilus under parts by weight of the present invention proportioning, draws
The activity of graceful lactobacillus, lactobacillus reuteri and lactobacillus bulgaricus, but intravaginal harmful bacteria can be killed.
Preferably, the parts by weight that the lactobacillus accounts for the expansible plug are 1-10 parts, for example, can be 1 part, 2 parts, 3
Part, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, preferably 3-8 parts.
Preferably, the lactobacillus includes lactobacillus acidophilus, Raman lactobacillus, lactobacillus reuteri and bulgarian milk bar
Bacterium forms.
Preferably, the lactobacillus acidophilus, Raman lactobacillus, lactobacillus reuteri and lactobacillus bulgaricus weight ratio
For (1-5):(3-8):(2-4):(5-10), such as can be 1:3:2:5、3:5:3:8、4:5:3:7、5:7:4:6、2:6:3:9
Or 3:4:4:7, preferably 3:5:3:8.
It is a discovery of the invention that can be adjusted with nisin synergy under the Lactobacillus species and composition and ratio
Vaginal flora is saved, the superiority of beneficial bacterium is kept, enhances vagina immunity and self-healing ability, effectively prevents bacterial vaginosis
It is scorching.
Preferably, the matrix includes Acrawax, natural acid ester, lipoidis matrix, water-soluble base, hydrogen
In carburetion or distillate oil any one or at least two combination, the combination for example can be Acrawax and natural
The combination of aliphatic ester, the combination of lipoidis matrix and water-soluble base, Acrawax, lipoidis matrix and distillate oil
Combination or the combination of lipoidis matrix, water-soluble base and hydrogenated oil and fat, preferably lipoidis matrix, water-soluble base and hydrogenation
The combination of oil.
Preferably, the weight ratio of the lipoidis matrix, water-soluble base and hydrogenated oil and fat is (1-5):(3-8):(1-4),
Such as can be 1:3:1、2:5:3、3:4:2、4:6:3、5:8:4、3:5:2 or 2:7:3, preferably 3:5:2.
It is a discovery of the invention that the matrix includes for the combination of lipoidis matrix, water-soluble base and hydrogenated oil and fat, and described group
The ratio of conjunction is 3:5:Physicochemical property is most stable when 2, and wetting is best with emulsifying effectiveness, promotes release and the drug effect of amphotericin B
It plays.
Preferably, the Acrawax be mixed fatty glycerides, it is propylene glycol stearate, fixed oil, hemizygous
At any one in fatty glyceride, semi-synthetic cocounut oil ester, Witepsol, semi-synthetic palm grease or semi-synthetic fruit of a cubeb litsea tree ester
Kind or at least two mixture, the mixture for example can be mixed fatty glycerides and fixed oil, stearic acid the third two
Alcohol ester and semi-synthetic fatty glyceride or semi-synthetic cocounut oil ester, Witepsol and semi-synthetic fruit of a cubeb litsea tree ester.
Preferably, the natural acid ester is to appoint in oleum sapii, spicebush oil, fennel fat, Ke Kemu fat or cocoa butter
It anticipates a kind of or at least two mixtures, the mixture for example can be oleum sapii and Ke Kemu fat, spicebush oil and Ke Kemu
Fat or spicebush oil, fennel fat and cocoa butter.
Preferably, the lipoidis matrix is lanolin and/or lanonol, preferably lanonol.
Preferably, the water-soluble base is polyethylene glycol 400, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol
6000, any one in glycerin gelatine, polyoxyl 40 stearate or poloxamer or at least two mixture, it is described
Mixture for example can be the combination of polyethylene glycol 400 and polyethylene glycol 1500, the combination of Macrogol 4000 and glycerin gelatine,
The combination of Macrogol 6000 and poloxamer, the combination of Macrogol 6000, glycerin gelatine and polyoxyl 40 stearate,
The combination of polyethylene glycol 400, polyethylene glycol 1500, Macrogol 4000 and poloxamer, preferably Macrogol 4000.
Preferably, the hydrogenated oil and fat is appointing in hydrogenated vegetable oil, hydrogenated groundnut, rilanit special or cotmar
It anticipates a kind of or at least two mixtures, the mixture for example can be the mixture of hydrogenated vegetable oil and rilanit special,
The mixture of the mixture or hydrogenated vegetable oil of hydrogenated groundnut and cotmar, hydrogenated groundnut and rilanit special.
Preferably, the distillate oil is fractionating palm oil and/or fractionated coconut oil.
Preferably, the matrix further includes emulsifier and/or sustained release agent.
Preferably, the matrix includes the sustained release of the emulsifier and 30-50 parts by weight of 10-20 parts by weight in parts by weight
Agent.
The parts by weight of the emulsifier are 10-20 parts, for example, can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15
Part, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts.
The parts by weight of the sustained release agent are 30-50 parts, for example, can be 30 parts, 32 parts, 34 parts, 35 parts, 36 parts, 38
Part, 39 parts, 40 parts, 42 parts, 43 parts, 44 parts, 46 parts, 47 parts, 48 parts, 49 parts or 50 parts.
It is a discovery of the invention that matrix includes emulsifier and sustained release agent, and the emulsifier and sustained release agent are according to described heavy
Amount number, which is combined, to control drug release rate with stable pharmaceutical ingredient, and drug effect is promoted to play, and increase amphotericin B in matrix
In dispersed homogeneous degree, improve the bioavilability of suppository.
Preferably, the emulsifier include in stearic acid, aluminum foil stearate or mono stearate glyceryl ester any one or extremely
Few two kinds of combination, such as can be the combination of stearic acid and aluminum stearate, the combination of aluminum stearate and glycerin monostearate,
Or the combination of stearic acid, aluminum stearate and glycerin monostearate, the preferably combination of stearic acid and mono stearate glyceryl ester, institute
The weight ratio for stating stearic acid and mono stearate glyceryl ester is (3-6):(1-3), such as can be 3:1、4:3、5:2、6:1、3:3 or
6:3。
Preferably, the sustained release agent includes any one in hydroxypropyl cellulose, sodium alginate, locust bean gum or laruyl alcohol
Or at least two mixture, such as can be the mixture of hydroxypropyl cellulose and sodium alginate, locust bean gum and laruyl alcohol
The mixture of mixture or sodium alginate, locust bean gum and laruyl alcohol, the preferably combination of hydroxypropyl cellulose and sodium alginate,
The weight ratio of the hydroxypropyl cellulose and sodium alginate is (2-6):1 for example can be 2:1、3:1、4:1、5:1 or 6:1.
Preferably, the vaginal expansion plug, the expandable carrier include any one in sliver, non-woven fabrics or elastomer
Kind or at least two combination, the combination for example can be sliver and non-woven fabrics or sliver and elastomer, preferably cotton
Item.
As optimal technical scheme, the vaginal expansion plug includes following component：
Second aspect, the present invention provides a kind of method preparing amphotericin B vaginal expansion plug as described in relation to the first aspect,
Include the following steps：
(1) preparation of drug containing matrix：
A) emulsifier and sustained release agent are placed in water-bath and are mixed, oil phase is made；
B) mixed liquor of amphotericin B and nisin will be contained as Aqueous dispersions in the oil phase of step a),
Obtain pre-emulsion；
C) pre-emulsion for obtaining step (b) carries out fast film emulsification, crosses microporous barrier, obtains drug containing matrix；
(2) drug containing matrix is poured into bolt mould, is inserted into expandable carrier, suppository is made in attachment sizing.
Preferably, the mixed liquor in the step b) further includes lactobacillus.
Preferably, it is described cross microporous barrier pressure be 0.1-2Mpa, such as can be 0.1Mpa, 0.3Mpa, 0.5Mpa,
0.6Mpa, 0.7Mpa, 0.9Mpa, 1.0Mpa, 1.2Mpa, 1.4Mpa, 1.5Mpa, 1.6Mpa, 1.8Mpa or 2.0Mpa.
Preferably, the aperture for crossing microporous barrier is 0.3-5 μm, for example, can be 0.3 μm, 0.5 μm, 0.7 μm, 1.0 μm,
1.2μm、1.4μm、1.6μm、1.8μm、2.0μm、2.3μm、2.5μm、2.7μm、3.0μm、3.2μm、3.5μm、3.7μm、4.0μ
M, 4.3 μm, 4.5 μm, 4.7 μm or 5.0 μm, preferably 0.5-3 μm.
It is a discovery of the invention that when the pore size of microporous barrier is in the range, the diameter of the drug matrices obtained after film is crossed
Suitable size, drug releasing rate is slow, extends local administration time, increases curative effect.
Compared with prior art, the present invention has the advantages that：
(1) amphotericin B is used for suppository formulation by the present invention, avoids causing to damage to stomach, and sustained-release administration extends drug
Amphotericin B and nisin is applied in combination in action time, synergistic, promotes drug effect to play, effectively antagonizes fungi
Property, bacterial vaginitis, reduce the side effect of amphotericin B；
(2) present invention is used cooperatively a variety of lactobacillus, adjusts vaginal flora environment, enhances vagina self-healing ability, described
Under the combination formula of lactobacillus, it is effectively increased vagina beneficial bacterium, pH is adjusted, inhibits the growth and breeding of pathogenic bacteria, is effectively prevented
Bacterial vaginitis；
(3) combination formula of matrix of the present invention can effectively maintain the dosage form and moisture of suppository, gentle in emulsifier
Under the cooperation for releasing agent, the amphotericin B vaginal expansion plug stable components, drug releasing rate is moderate, increases the biology of drug
Availability, and by the microporous barrier of the pore diameter range, adjust the rate of release of drug, extend drug effect in affected part when
Between, it can effectively treat vaginitis.
Specific implementation mode
Further to illustrate the present invention technological means and its effect taken, below by way of specific implementation mode come into
One step illustrates technical scheme of the present invention, but the present invention is not limited in scope of embodiments.
Embodiment 1
Preparation method：
(1) preparation of drug containing matrix：
A) emulsifier and sustained release agent are placed in water-bath and are mixed, oil phase is made；
B) mixed liquor of amphotericin B and nisin will be contained as Aqueous dispersions in the oil phase of step a),
Obtain pre-emulsion；
C) pre-emulsion for obtaining step (b) carries out fast film emulsification, and 0.1MPa crosses microporous barrier, and aperture is 1.5 μm, is obtained
Drug containing matrix；
(2) drug containing matrix is poured into bolt mould, is inserted into expandable carrier, suppository is made in attachment sizing.
Embodiment 2
Preparation method：
(1) preparation of drug containing matrix：
A) emulsifier and sustained release agent are placed in water-bath and are mixed, oil phase is made；
B) mixed liquor of amphotericin B and nisin will be contained as Aqueous dispersions in the oil phase of step a),
Obtain pre-emulsion；
C) pre-emulsion for obtaining step (b) carries out fast film emulsification, and 2MPa crosses microporous barrier, and aperture is 0.3 μm, is contained
Medicine matrix；
(2) drug containing matrix is poured into bolt mould, is inserted into expandable carrier, suppository is made in attachment sizing.
Embodiment 3
Preparation method：
(1) preparation of drug containing matrix：
A) emulsifier and sustained release agent are placed in water-bath and are mixed, oil phase is made；
B) mixed liquor of amphotericin B and nisin will be contained as Aqueous dispersions in the oil phase of step a),
Obtain pre-emulsion；
C) pre-emulsion for obtaining step (b) carries out fast film emulsification, and 1MPa crosses microporous barrier, and aperture is 5 μm, obtains drug containing
Matrix；
(2) drug containing matrix is poured into bolt mould, is inserted into expandable carrier, suppository is made in attachment sizing.
Embodiment 4
Preparation method：
(1) preparation of drug containing matrix：
A) emulsifier and sustained release agent are placed in water-bath and are mixed, oil phase is made；
B) mixed liquor of amphotericin B and nisin will be contained as Aqueous dispersions in the oil phase of step a),
Obtain pre-emulsion；
C) pre-emulsion for obtaining step (b) carries out fast film emulsification, and 0.5MPa crosses microporous barrier, and aperture is 0.5 μm, is obtained
Drug containing matrix；
(2) drug containing matrix is poured into bolt mould, is inserted into expandable carrier, suppository is made in attachment sizing.
Embodiment 5
Preparation method：
(1) preparation of drug containing matrix：
A) emulsifier and sustained release agent are placed in water-bath and are mixed, oil phase is made；
B) mixed liquor of amphotericin B and nisin will be contained as Aqueous dispersions in the oil phase of step a),
Obtain pre-emulsion；
C) pre-emulsion for obtaining step (b) carries out fast film emulsification, and 1.5MPa crosses microporous barrier, and aperture is 3 μm, is contained
Medicine matrix；
(2) drug containing matrix is poured into bolt mould, is inserted into expandable carrier, suppository is made in attachment sizing.
Embodiment 6
The preparation method is the same as that of Example 1.
Embodiment 7
The preparation method is the same as that of Example 1.
Embodiment 8
The preparation method is the same as that of Example 1.
Embodiment 9
The preparation method is the same as that of Example 1.
Embodiment 10
The preparation method is the same as that of Example 1.
Embodiment 11
The preparation method is the same as that of Example 1.
Embodiment 12
The preparation method is the same as that of Example 1.
Embodiment 13
The preparation method is the same as that of Example 1.
Embodiment 14
The preparation method is the same as that of Example 1.
Embodiment 15
The preparation method is the same as that of Example 1.
Embodiment 16
The preparation method is the same as that of Example 1.
Embodiment 17
The preparation method is the same as that of Example 1.
Embodiment 18
The preparation method is the same as that of Example 1.
Embodiment 19
The preparation method is the same as that of Example 1.
Embodiment 20
The preparation method is the same as that of Example 1.
Embodiment 21
The preparation method is the same as that of Example 1.
Embodiment 22
The preparation method is the same as that of Example 1.
Embodiment 23
The preparation method is the same as that of Example 1.
Embodiment 24
Compared with Example 1, cross micropore film pressure be 3MPa, other components with the preparation method is the same as that of Example 1.
Embodiment 25
Compared with Example 1, micropore membrane aperture be 0.1 μm, other components with the preparation method is the same as that of Example 1.
Embodiment 26
Compared with Example 1, micropore membrane aperture be 3.5 μm, other components with the preparation method is the same as that of Example 1.
Comparative example 1
Compared with Example 1, amphotericin B, and the weight of lipoidis matrix, water-soluble base and hydrogenated oil and fat are not added
Number is adjusted to 198g, other components and the preparation method is the same as that of Example 1.
Comparative example 2
Compared with Example 1, nisin is not added, and lipoidis matrix, water-soluble base and hydrogenated oil and fat
Parts by weight are adjusted to 192g, other components and the preparation method is the same as that of Example 1.
Comparative example 3
Compared with Example 1, amphotericin B additive amount is 5g, and lipoidis matrix, water-soluble base and hydrogenated oil and fat
Parts by weight are adjusted to 193g, other components and the preparation method is the same as that of Example 1.
Comparative example 4
Compared with Example 1, amphotericin B additive amount is 30g, and lipoidis matrix, water-soluble base and hydrogenated oil and fat
Parts by weight be adjusted to 168g, other components and the preparation method is the same as that of Example 1.
Comparative example 5
Compared with Example 1, the additive amount of nisin is 10g, and lipoidis matrix, water-soluble base and hydrogen
The parts by weight of carburetion are adjusted to 172g, other components and the preparation method is the same as that of Example 1.
Clinical test
One, research method
Research approach is with reference to related " the gynemetrics's genital inflammation of Ministry of Health of the People's Republic of China's new drug clinical guidance principle
The clinical verification of local application " content and formulate.
1. testing case：It accepts patient totally 168 for medical treatment, makes a definite diagnosis bacterial vaginitis patient 84, fungi through gynecologial examination
Vaginosis patient 84, age between 18-62 Sui, exclude gestation and nursing period patient；
2. diagnostic criteria：
Symptom：Pruritus vulvue, cusalgia, or with frequent micturition, urgent urination, odynuria；
Gynecologial examination：Bacterial vaginitis secretory substance is even, thin, has a fish like smell；Vulvovaginal candidiasis, have compared with
More white bean dregs sample leukorrhea；
Laboratory examination：Bacterial vaginitis can discover a clue in secretion under microscope cell, fungi vaginosis,
Smear detects, and looks for pseudohypha under microscope, positive rate is up to 60%；
3. grouping and administration：By 84 bacterial vaginitis, it is randomly divided into treatment group 69 and control group 15；By 84
Fungi vaginosis patient is randomly divided into treatment group 69 and control group 15；Embodiment 1-23 gives respectively in the above treatment group
Vaginal expansion plug, every group of three people, control group gives the vaginal expansion plug of comparative example 1-5, every group of three people respectively；
4. observation item
4.1 therapeutic observations
(1) symptom；
(2) gynecologial examination：Including vulva, vagina, uterine neck and vaginal fluid inspection；
(3) laboratory examination：To vaginal fluid inspection, including under mirror, smear；
(4) Bacteria Culture；
4.2 safety observations
(1) general physical examination project；
(2) blood, urine, feces routine test；
(3) heart, Liver and kidney function inspection；
4.3 adverse reactions are observed
Any abnormal symptom occurred during medication, sign, laboratory examination all answer serious analysis, carefully differentiate；
5. efficacy assessment standard：
Recovery from illness：Symptom disappears, and gynecologial examination and laboratory examination are normal；
It is effective：Symptom is substantially reduced, and gynecologial examination and laboratory examination are clearly better；
Effectively：Symptom is mitigated, and gynecologial examination and laboratory examination are improved；
In vain：It is unchanged before relatively being treated after treatment；
6. treatment results：After 4 courses for the treatment of are administered in patient, therapeutic effect is as shown in table 1.
Table 1
As can be seen from Table 1, amphotericin B vaginal expansion plug has very well bacterial vaginitis and colpomycosis
The effect of.Comparing embodiment 1 and comparative example 1-5 it is found that the combination matching of amphotericin B and nisin to treating vagina
Scorching important function, indispensable, the two is synergistic.Comparing embodiment 1 and embodiment 6-11 is it is found that the addition of lactobacillus can
Vaginal flora is effectively adjusted, increases vagina self-healing ability, and under the conditions of composition and ratio of the present invention, best results.Compare
Embodiment 1 and embodiment 12-23 it is found that matrix influence of the selection with ratio to amphotericin B vaginal expansion plug performance drug effect,
Medicaments uniformity dispersion can be effectively facilitated under matrix species of the present invention and proportioning, improve bioavilability.Compare reality
It applies example 1 and implements 23-26 it is found that the aperture of microporous barrier and excessively film pressure all influence the sizing of drug and drug effect plays.
To sum up, amphotericin B vaginal expansion plug of the invention, by combination using amphotericin B, nisin and
The active ingredients such as lactobacillus make to play synergistic effect between each component, matrix, emulsifier and sustained release agent are applied in combination, improves drug
Dispersion degree and bioavilability effectively treat bacterial vaginitis and colpomycosis.
Applicant states that the present invention illustrates the method detailed of the present invention, but the present invention not office 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 implement.Technical field
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, the selection etc. of concrete mode, all fall within protection scope of the present invention and the open scope.
Claims (10)
1. a kind of amphotericin B vaginal expansion plug, which is characterized in that the expansible plug includes amphotericin B, streptococcus lactis
Element, matrix and expandable expandable carrier, the parts by weight of each ingredient of expansible plug are：
2. vaginal expansion plug according to claim 1, which is characterized in that the expansible plug further includes lactobacillus；
Preferably, the parts by weight that the lactobacillus accounts for the expansible plug are 1-10 parts, preferably 3-8 parts.
3. vaginal expansion plug according to claim 1 or 2, which is characterized in that the lactobacillus includes lactobacillus acidophilus, draws
Graceful lactobacillus, lactobacillus reuteri and lactobacillus bulgaricus composition；
Preferably, the weight ratio of the lactobacillus acidophilus, Raman lactobacillus, lactobacillus reuteri and lactobacillus bulgaricus is
(1-5):(3-8):(2-4):(5-10), preferably 3:5:3:8.
4. according to claim 1-3 any one of them vaginal expansion plugs, which is characterized in that the matrix includes synthetic fatty acid
Any one in ester, natural acid ester, lipoidis matrix, water-soluble base, hydrogenated oil and fat or distillate oil or at least two
Combination, the preferably combination of lipoidis matrix, water-soluble base and hydrogenated oil and fat；
Preferably, the weight ratio of the lipoidis matrix, water-soluble base and hydrogenated oil and fat is (1-5):(3-8):(1-4), preferably
It is 3:5:2.
5. according to claim 1-4 any one of them vaginal expansion plugs, which is characterized in that the Acrawax is mixing
Fatty glyceride, propylene glycol stearate, fixed oil, semi-synthetic fatty glyceride, semi-synthetic cocounut oil ester, Witepsol,
In semi-synthetic palm grease or semi-synthetic fruit of a cubeb litsea tree ester any one or at least two mixture；
Preferably, the natural acid ester is any one in oleum sapii, spicebush oil, fennel fat, Ke Kemu fat or cocoa butter
Kind or at least two mixture；
Preferably, the lipoidis matrix is lanolin and/or lanonol；
Preferably, the water-soluble base is polyethylene glycol 400, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol
6000, any one in glycerin gelatine, polyoxyl 40 stearate or poloxamer or at least two mixture, preferably
For Macrogol 4000；
Preferably, the hydrogenated oil and fat is any one in hydrogenated vegetable oil, hydrogenated groundnut, rilanit special or cotmar
Kind or at least two mixture；
Preferably, the distillate oil is fractionating palm oil and/or fractionated coconut oil.
6. according to claim 1-5 any one of them vaginal expansion plugs, which is characterized in that the matrix further includes emulsifier
And/or sustained release agent；
Preferably, the matrix includes the sustained release agent of the emulsifier and 30-50 parts by weight of 10-20 parts by weight in parts by weight；
Preferably, the emulsifier includes any one in stearic acid, aluminum foil stearate or mono stearate glyceryl ester or at least two
The combination of kind, the preferably combination of stearic acid and mono stearate glyceryl ester, the weight of the stearic acid and mono stearate glyceryl ester
Than for (3-6):(1-3)；
Preferably, the sustained release agent include in hydroxypropyl cellulose, sodium alginate, locust bean gum or laruyl alcohol any one or extremely
Few two kinds of mixture, the preferably combination of hydroxypropyl cellulose and sodium alginate, the hydroxypropyl cellulose and sodium alginate
Weight ratio be (2-6):1.
7. according to claim 1-6 any one of them vaginal expansion plugs, which is characterized in that the expandable carrier include sliver,
In non-woven fabrics or elastomer any one or at least two combination, preferably sliver.
8. a kind of method preparing the vaginal expansion plug as described in claim any one of 1-7, which is characterized in that including walking as follows
Suddenly：
(1) preparation of drug containing matrix：
A) emulsifier and sustained release agent are placed in water-bath and are mixed, oil phase is made；
B) mixed liquor of amphotericin B and nisin will be contained as Aqueous dispersions in the oil phase of step a), obtained
Pre-emulsion；
C) pre-emulsion for obtaining step (b) carries out fast film emulsification, crosses microporous barrier, obtains drug containing matrix；
(2) drug containing matrix is poured into bolt mould, is inserted into expandable carrier, suppository is made in attachment sizing.
9. according to the method described in claim 8, it is characterized in that, the mixed liquor in step b) further includes lactobacillus.
10. method according to claim 8 or claim 9, which is characterized in that the pressure for crossing microporous barrier is 0.1-2MPa；
Preferably, the aperture for crossing microporous barrier is 0.3-5 μm, preferably 0.5-3 μm.
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| CN113694036A (en) * | 2021-09-18 | 2021-11-26 | 华北制药股份有限公司 | Amphotericin B vaginal effervescent tablet and preparation method thereof |
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Application publication date: 20180724 |