CN110638744A - Vaginal effervescent suppository and preparation method and application thereof - Google Patents

Vaginal effervescent suppository and preparation method and application thereof Download PDF

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Publication number
CN110638744A
CN110638744A CN201911094603.1A CN201911094603A CN110638744A CN 110638744 A CN110638744 A CN 110638744A CN 201911094603 A CN201911094603 A CN 201911094603A CN 110638744 A CN110638744 A CN 110638744A
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suppository
combination
effervescent
drugs
parts
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邱明世
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Harbin OT Pharmaceutical Co Ltd
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Harbin OT Pharmaceutical Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/13—Amines
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284—Atractylodes
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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    • A61K38/21—Interferons [IFN]
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • A—HUMAN NECESSITIES
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Abstract

The invention provides a vaginal effervescent suppository, a preparation method and application thereof. The effervescent suppository provided by the invention expands the expansion carrier through the effervescent effect, increases the contact area of the drug effect components in the suppository and the vagina, increases the administration area, improves the drug effect duration, improves the antibacterial and anti-inflammatory capabilities, has the effective rate of 99.8% for treating bacterial vaginitis, 100% for treating fungal vaginitis and 100% for treating bacterial vaginitis.

Description

Vaginal effervescent suppository and preparation method and application thereof
Technical Field
The invention belongs to the field of medical treatment, relates to a vaginal suppository and a preparation method thereof, and particularly relates to a vaginal effervescent suppository and a preparation method and application thereof.
Background
Vaginitis is a common gynecological disease and seriously affects normal working and life of women. The mycotic vaginitis is caused by candida albicans, and the candida is also called candida and is the most common pathogenic bacterium in fungi. The current common administration forms comprise solutions such as suppositories, tablets, ointments, gel semi-solid preparations, lotions and sprays. The suppository can directly act on the affected part, improve the local drug concentration and reduce the toxic and side effects of the whole body, and is an ideal administration mode.
CN 104840485A discloses an active carbon suppository for treating cervical erosion and a preparation method thereof, wherein the suppository consists of suppository granules and medical absorbent gauze wrapped outside the suppository granules; the suppository granule is composed of medicinal activated carbon fiber ACF, carbomer, sodium carboxymethylcellulose, mixed fatty glyceride, gelatin, glycerol and purified water, is used for treating vaginitis and other gynecological inflammations, and can adsorb various pathogenic bacteria and viruses into fiber pores to change the living environment and kill the pathogenic bacteria and viruses, so that the effects of diminishing inflammation, relieving pain, stopping bleeding, deodorizing and sterilizing are achieved, cell growth is promoted to accelerate tissue regeneration, the normal internal environment of the vagina is not damaged, the growth of lactobacillus is not influenced, and the bacteria cannot generate drug resistance. However, the suppository provided by the patent has a small effective area, which is not favorable for eliminating bacterial infection in the deep vagina.
CN 101632658B discloses a medicinal preparation for treating vaginitis and a preparation method thereof, wherein the medicinal preparation is composed of ornidazole, sodium bicarbonate, citric acid monohydrate, semisynthetic fatty glyceride and polysorbate 80. The effervescent suppository is prepared by adding foaming agent into ornidazole, so that effervescence is generated during use to accelerate the melting of the suppository and the release of the medicine. The invention has the advantages of both effervescent and suppository, and the medicine is easier to melt and absorb, but the preparation provided by the method has small administration area and quick release of the medicine effect, and is not beneficial to the long-acting release of the effective components of the medicine.
CN 108324932A discloses a vaginal expansion suppository, a preparation method and an application thereof, wherein the expansion suppository comprises lactoferrin, Bingpeng powder, a matrix and an expandable expansion carrier, and the expansion suppository further comprises lactobacillus and/or lactococcus. The expandable vaginal suppository provided by the patent improves the vaginal flora environment by combining and utilizing the active ingredients of the Bingpeng powder, the lactic acid bacteria and the like to synergistically enhance the drug effect, and improves the bioavailability by combining and proportioning the ingredients of the matrix, the stabilizer, the emulsifier, the corrosion inhibitor and the like. However, the method only uses the swelling carrier to increase the administration area, and the vagina fold can not be effectively administered.
Shandong et al published a preparation and quality control article titled compound cnidium effervescent suppository (Jiangsu traditional Chinese medicine (2002),23(9):40-41), which indicates that the effervescent action can increase the contact area between the drug and vagina and make the drug penetrate deep into folds of vaginal mucosa to fully exert the drug effect, but the article does not consider the retention time of the drug in vivo.
Therefore, the development of the vaginal effervescent suppository with large administration area and long drug effect duration has important significance for improving the cure rate of the vaginitis.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides the vaginal effervescent suppository and the preparation method and the application thereof, the vaginal effervescent suppository has large administration area and sustained release of drug effect, can effectively administer drug to the deep vagina, and has good curative effect on colpitis mycotica, viral vaginitis and bacterial vaginitis.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides a vaginal effervescent suppository, which comprises the following components in parts by weight:
Figure BDA0002267920670000031
the effervescent agent in the vaginal effervescent suppository provided by the invention is matched with the expansion carrier, the expansion carrier is expanded due to the disintegration of the effervescent agent, the administration area of the drug effect component is increased, and the drug effect component can reach the fold position which is not easy to reach by a common medicament, so that the administration effect is improved, and the antibacterial and anti-inflammatory capabilities are improved.
The drug effect component is 10-80 parts, for example, 10 parts, 15 parts, 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, 45 parts, 50 parts, 55 parts, 60 parts, 65 parts, 70 parts, 75 parts or 80 parts.
The effervescent agent is 8-14 parts, for example, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts or 14 parts.
The matrix is 150-240 parts, and may be, for example, 150 parts, 155 parts, 160 parts, 165 parts, 170 parts, 175 parts, 180 parts, 185 parts, 190 parts, 195 parts, 200 parts, 205 parts, 210 parts, 215 parts, 220 parts, 225 parts, 230 parts, 235 parts or 240 parts.
The swelling carrier is 120-160 parts, and may be, for example, 120 parts, 125 parts, 130 parts, 135 parts, 140 parts, 145 parts, 150 parts, 155 parts or 160 parts.
Preferably, the pharmacodynamic component includes any one or a combination of at least two of an antibacterial drug, an antifungal drug, an antiviral drug or a traditional Chinese medicine extract, and typical but non-limiting combinations include a combination of an antibacterial drug and an antifungal drug, a combination of an antifungal drug and an antiviral drug, a combination of an antibacterial drug, an antiviral drug and an antifungal drug, a combination of an antibacterial drug and a traditional Chinese medicine extract, a combination of an antifungal drug and a traditional Chinese medicine extract, a combination of an antiviral drug and a traditional Chinese medicine extract, a combination of an antifungal drug, an antiviral drug and a traditional Chinese medicine extract or a combination of an antibacterial drug, an antifungal drug, an antiviral drug and a traditional Chinese medicine extract, preferably a combination of an antibacterial drug, an antifungal drug, an antiviral drug and a traditional Chinese medicine extract.
Preferably, the mass ratio of the antibacterial drug, the antifungal drug, the antiviral drug and the traditional Chinese medicine extract is (1-3): (1-3): 1-3, and may be, for example, 1:1:1, 2:2:2:1, 3:3:3:1, 2:1:2:1, 2:1:1:1, 1:2:2:1 or 1:3:2:1, preferably 1:1:1: 1.
Preferably, the antibacterial drug comprises one or a combination of at least two of nitroimidazole derivative drugs, penicillins, cephalosporins, aminoglycosides, macrolides, lincomycins, quinolones or chlorhexidine acetate, and typical but non-limiting combinations include a combination of nitroimidazole derivative drugs and penicillins, a combination of penicillins and cephalosporins, a combination of nitroimidazole derivative drugs, aminoglycosides, macrolides and lincomycins, or a combination of nitroimidazole derivative drugs, penicillins, cephalosporins, aminoglycosides, macrolides, lincomycins and quinolones, preferably a combination of nitroimidazole derivative drugs.
Preferably, the nitroimidazole derivative drug includes any one or a combination of at least two of metronidazole, secnidazole, ornidazole, metronidazole or tinidazole, typical but non-limiting combinations include combinations of metronidazole and metronidazole, ornidazole and tinidazole, metronidazole, dinitrimidazole, secnidazole and secnidazole or combinations of metronidazole, dinitrimidazole, isotrudazole, ornidazole, metronidazole and tinidazole.
Preferably, the antifungal drug comprises any one of flucytosine, amphotericin B, nystatin, globtinomycin, mepartricin, fluconazole, clotrimazole, econazole nitrate or itraconazole or a combination of at least two thereof, typical but non-limiting combinations include a combination of flucytosine and amphotericin B, a combination of amphotericin B, nystatin and globithromycin, a combination of flucytosine, mepartricin, fluconazole and itraconazole or a combination of flucytosine, amphotericin B, nystatin, globithromycin, mepartricin, fluconazole and itraconazole.
Preferably, the antiviral drug comprises any one or a combination of at least two of amantadine, acyclovir or interferon, typical but non-limiting combinations include amantadine in combination with acyclovir, amantadine in combination with interferon or amantadine, acyclovir and interferon.
Preferably, the raw materials of the traditional Chinese medicine extract comprise any one or a combination of at least two of radix sophorae flavescentis, cortex phellodendri, radix scutellariae, curcuma zedoary, clam shell powder, red lead, catechu, frankincense, myrrh, pig gall powder, rheum officinale, fructus cnidii, herba epimedii, radix dipsaci, spina gleditsiae, cassia twig, fructus aurantii, matrine, leonurus heterophyllus, prepared rehmannia root, angelica sinensis, radix paeoniae alba, rhizoma atractylodis macrocephalae, poria cocos, codonopsis pilosula, liquorice, donkey-hide gelatin, cinnamon, andrographis paniculata. For example, it can be the combination of motherwort and prepared rehmannia root, the combination of Chinese angelica and white atractylodes rhizome, the combination of white peony root and white atractylodes rhizome, the combination of white atractylodes rhizome, tuckahoe and liquorice, the combination of donkey-hide gelatin, cinnamon, common andrographis herb and borneol, the combination of ginseng, borneol, astragalus root and tuber fleeceflower root or the combination of Chinese angelica, white peony root, white atractylodes rhizome, tuckahoe, borneol and astragalus root.
The traditional Chinese medicine extract is extracted by using a conventional method, and can be any one of a water decoction method, an immersion method, a percolation method, a modified gelatin method, a reflux method, a solvent extraction method, a steam distillation method or a sublimation method, and can be reasonably selected by a person skilled in the art according to process requirements.
Preferably, the effervescent agent consists of an acid component and a base component.
Preferably, the acid component comprises any one or combination of at least two of tartaric acid, citric acid or potassium hydrogen tartrate, typical but non-limiting combinations include combinations of tartaric acid and citric acid, citric acid and potassium hydrogen tartrate or tartaric acid, citric acid and potassium hydrogen tartrate.
Preferably, the alkali component comprises sodium bicarbonate and/or potassium bicarbonate.
Preferably, the mass ratio of the acid component to the base component is (3-8):1, and may be, for example, 3:1, 4:1, 5:1, 6:1, 7:1 or 8:1, preferably (4-6): 1. The effervescent agent contains higher acid component than alkali component, and can regulate vaginal environment within proper acidic pH range, and the acidic pH can inhibit bacteria growth and reproduction.
Preferably, the effervescent vaginal suppository further comprises a foaming agent, and the foaming agent is 1-5 parts by weight, for example, 1 part, 2 parts, 3 parts, 4 parts or 5 parts, preferably 2-4 parts.
Preferably, the foaming agent comprises any one of tween 20, tween 60, tween 80, sodium dodecyl sulfate and linear sodium dodecyl benzene sulfonate or a combination of at least two of them, typical but non-limiting combinations include a combination of tween 20 and tween 60, a combination of tween 20 and tween 80, a combination of tween 60 and sodium dodecyl sulfate or a combination of tween 20, tween 60 and linear sodium dodecyl benzene sulfonate, preferably a combination of tween 60 and sodium dodecyl sulfate.
Preferably, the matrix comprises a water-soluble matrix.
Preferably, the water-soluble base comprises any one of or a combination of at least two of glycerogelatin, polyethylene glycol 400, polyethylene glycol 1000, and polyethylene glycol 4000, typical but non-limiting combinations include a combination of glycerogelatin and polyethylene glycol 400, a combination of polyethylene glycol 400 and polyethylene glycol 1000, or a combination of glycerogelatin, polyethylene glycol 1000 and polyethylene glycol 4000, preferably a combination of glycerogelatin and polyethylene glycol 4000.
The matrix formed by the combination of the glycerogelatin and the polyethylene glycol 4000 can improve the stability of the suppository, and the release speed of the active ingredients of the medicine can be controlled by controlling the proportion of the glycerogelatin and the polyethylene glycol 4000.
Preferably, the mass ratio of the glycerogelatin to the polyethylene glycol 4000 is (1-5):1, for example, 1:1, 2:1, 3:1, 4:1 or 5:1, preferably (2-4): 1.
Preferably, a cyclodextrin metal organic framework is also added to the matrix.
The cyclodextrin metal organic framework can act synergistically with antibacterial drugs, antifungal drugs, antiviral drugs and traditional Chinese medicine extracts, the structural characteristics of the cyclodextrin metal organic framework enable the cyclodextrin metal organic framework to adsorb the antibacterial drugs, the antifungal drugs, the antiviral drugs and the traditional Chinese medicine extracts, and the cyclodextrin metal organic framework is easy to disintegrate in the vaginal environment, so that the release speed of active ingredients of the drugs can be controlled.
Preferably, the mass ratio of the cyclodextrin metal-organic framework to the polyethylene glycol 4000 is (1-2: 1), and may be, for example, 1:1, 1.2:1, 1.4:1, 1.6:1, 1.8:1, or 2: 1.
Preferably, methylparaben is further added to the matrix, and the methylparaben has broad-spectrum antibacterial activity and a preservative effect and can improve the stability of the effervescent suppository.
Preferably, the ratio of methyl hydroxybenzoate to polyethylene glycol 4000 is 1 (5-10), and may be, for example, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10, preferably 1 (6-8).
Preferably, an emulsifier and/or a corrosion inhibitor is also added to the matrix.
Preferably, the emulsifier is 12-16 parts by weight, such as 12 parts, 13 parts, 14 parts, 15 parts or 16 parts, preferably 13-15 parts;
preferably, the corrosion inhibitor is 32 to 48 parts by weight, such as 32 parts, 34 parts, 36 parts, 38 parts, 40 parts, 42 parts, 44 parts, 46 parts or 48 parts, preferably 36 to 42 parts;
preferably, the emulsifier comprises any one or a combination of at least two of stearic acid, aluminum stearate or magnesium stearate, typical but non-limiting combinations include combinations of stearic acid and aluminum stearate, stearic acid and magnesium stearate or stearic acid, aluminum stearate and magnesium stearate, preferably stearic acid and magnesium stearate.
Preferably, the weight ratio of stearic acid to magnesium stearate is (1-3):1, for example 1:1, 2:1 or 3:1, preferably 2: 1.
Preferably, the sustained release agent comprises any one or a mixture of at least two of hydroxypropyl cellulose, sodium alginate, locust bean gum or lauryl alcohol, and typical but non-limiting combinations include a combination of hydroxypropyl cellulose and sodium alginate, a combination of sodium alginate and locust bean gum, a combination of hydroxypropyl cellulose, locust bean gum and lauryl alcohol or a combination of hydroxypropyl cellulose, sodium alginate, locust bean gum and lauryl alcohol, preferably a combination of hydroxypropyl cellulose and sodium alginate.
Preferably, the weight ratio of the hydroxypropyl cellulose to the sodium alginate is (2-6: 1), for example, 2:1, 3:1, 4:1, 5:1 or 6:1, preferably (3-5: 1).
Preferably, the expansion carrier comprises any one or a combination of at least two of a tampon, a nonwoven or an elastic fiber, typical but non-limiting combinations comprising a tampon and a nonwoven, a tampon and an elastic fiber or a tampon, a nonwoven or an elastic fiber, preferably a tampon.
Preferably, the surface of the expanded carrier is coated with a conditioning agent.
Preferably, the weight part of the regulator is 5 to 20 parts, for example, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, preferably 8 to 15 parts.
Preferably, the conditioning agent comprises any one or a combination of at least two of hydroxymethyl cellulose, metformin or sodium alginate, typical but non-limiting combinations include hydroxymethyl cellulose in combination with metformin, metformin in combination with sodium alginate or hydroxymethyl cellulose, metformin and sodium alginate, preferably hydroxymethyl cellulose, metformin and sodium alginate.
Preferably, the weight ratio of the hydroxymethyl cellulose to the metformin to the sodium alginate is (4-8): (2-4):1, and can be, for example, 4:2:1, 5:3:1, 6:2:1, 7:4:1 or 8:3:1, preferably 6:3: 1.
According to the vaginal effervescent suppository provided by the invention, the effervescent suppository comprises the following components in parts by weight:
Figure BDA0002267920670000081
in a second aspect, the present invention also provides a process for the preparation of an effervescent vaginal suppository as defined in the first aspect, comprising the steps of:
(1) mixing emulsifier, sustained release agent, effervescent agent and foaming agent in water bath to obtain oil phase;
(2) dispersing a mixed solution containing antibacterial drugs, antifungal drugs, antiviral drugs, traditional Chinese medicine extracts and cyclodextrin metal organic frameworks into the oil phase in the step (1) as a water phase to obtain a pre-emulsion;
(3) carrying out rapid membrane emulsification on the pre-emulsion obtained in the step (2), and passing through a microporous membrane to obtain a drug-containing matrix;
(4) pouring the matrix containing the medicine into a suppository mold, inserting the expansion carrier, and adhering and shaping to obtain the suppository;
(5) and (4) coating and/or impregnating a regulator on the surface of the expansion carrier of the suppository, and drying to obtain the vaginal effervescent suppository.
Preferably, the dispersing method in step (2) is to slowly drop the aqueous phase into the oil phase.
Preferably, the slow dropping speed is 5-20mL/min, for example, 5mL/min, 6mL/min, 7mL/min, 8mL/min, 9mL/min, 10mL/min, 11mL/min, 12mL/min, 13mL/min, 14mL/min, 15mL/min, 16mL/min, 17mL/min, 18mL/min, 19mL/min or 20mL/min, preferably 10-15 mL/min.
Preferably, the dispersion is also accompanied by ultrasound assistance.
Preferably, the ultrasound-assisted time is 20-60min, for example 20min, 30min, 40min, 50min or 60min, preferably 30-40 min.
Preferably, the frequency of the ultrasonic assistance is 25-80kHz, and may for example be 25kHz, 30kHz, 35kHz, 40kHz, 45kHz, 50kHz, 55kHz, 60kHz, 65kHz, 70kHz, 75kHz or 80kHz, preferably 40-60 kHz.
Preferably, the pressure of the microporous membrane in step (3) is 0.5 to 1.5MPa, and may be, for example, 0.5MPa, 0.6MPa, 0.7MPa, 0.8MPa, 0.9MPa, 1.0MPa, 1.1MPa, 1.2MPa, 1.3MPa, 1.4MPa or 1.5MPa, preferably 0.8 to 1.2 MPa.
Preferably, the pore size of the microporous membrane is 0.5 to 3 μm, and may be, for example, 0.5 μm, 0.6 μm, 0.7 μm, 0.8 μm, 0.9 μm, 1.0 μm, 1.2 μm, 1.4 μm, 1.6 μm, 1.8 μm, 2 μm, 2.2 μm, 2.4 μm, 2.6 μm, 2.8 μm, or 3 μm, preferably 1 to 2 μm.
Preferably, the drying of step (5) is vacuum drying.
In a third aspect, the use of an effervescent vaginal suppository as described in the first aspect for the manufacture of a medicament and/or agent for the treatment of vaginitis.
Compared with the prior art, the invention has the beneficial effects that:
the effervescent suppository provided by the invention expands the expansion carrier through the effervescent effect, increases the contact area of the drug effect components in the suppository and the vagina, increases the administration area, improves the antibacterial and anti-inflammatory capabilities, has the treatment effective rate of 99.8 percent on bacterial vaginitis, has the treatment effective rate of 100 percent on fungal vaginitis and has the treatment effective rate of 100 percent on bacterial vaginitis, and the matrix of the effervescent suppository provided by the invention can prolong the release time of the drug components and improve the persistence of the drug effect.
Detailed Description
To further illustrate the technical means and effects of the present invention, the following embodiments further illustrate the technical solutions of the present invention, but the present invention is not limited to the scope of the embodiments.
I) Suppository preparation
Example 1
This example provides an effervescent vaginal suppository having the composition shown in table 1.
TABLE 1
Figure BDA0002267920670000101
Figure BDA0002267920670000111
The preparation method of the vaginal effervescent suppository comprises the following steps:
(1) mixing the emulsifier, the sustained release agent, the effervescent agent and the foaming agent in the formula ratio in a water bath to prepare an oil phase;
(2) slowly dripping a mixed solution containing metronidazole and cyclodextrin metal organic framework in a formula amount as a water phase into the oil phase in the step (1), and carrying out ultrasonic treatment, wherein the ultrasonic auxiliary time is 35min, and the ultrasonic auxiliary frequency is 50kHz, so as to obtain a pre-emulsion, and the dripping speed is 12 mL/min;
(3) carrying out rapid membrane emulsification on the pre-emulsion obtained in the step (2), and passing through a microporous membrane with the aperture of 1.5 mu m under the pressure of 1MPa to obtain a drug-containing matrix;
(4) pouring the matrix containing the medicine into a suppository mold, inserting the expansion carrier, and adhering and shaping to obtain the suppository;
(5) and (4) impregnating a regulator on the surface of the expansion carrier of the suppository in the step (4), and drying in vacuum to obtain the vaginal effervescent suppository.
Example 2
This example provides an effervescent vaginal suppository and method of preparation, which is the same as example 1 except that metronidazole is replaced with an equal weight portion of amphotericin B.
Example 3
This example provides an effervescent vaginal suppository and method of preparation, which is the same as example 1 except that metronidazole is replaced with an equal weight portion of interferon.
Example 4
This example provides an effervescent vaginal suppository having the composition shown in table 2.
TABLE 2
Figure BDA0002267920670000121
The preparation method of the vaginal effervescent suppository comprises the following steps:
(1) mixing the emulsifier, the sustained release agent, the effervescent agent and the foaming agent in the formula ratio in a water bath to prepare an oil phase;
(2) slowly dripping a mixed solution containing metronidazole, nystatin, amantadine, a white atractylodes rhizome extract and a cyclodextrin metal organic framework in a formula amount as a water phase into the oil phase in the step (1), and performing ultrasonic treatment, wherein the ultrasonic auxiliary time is 35min, and the ultrasonic auxiliary frequency is 50kHz to obtain a pre-emulsion, wherein the dripping speed is 12 mL/min;
(3) carrying out rapid membrane emulsification on the pre-emulsion obtained in the step (2), and passing through a microporous membrane with the aperture of 1.5 mu m under the pressure of 1MPa to obtain a drug-containing matrix;
(4) pouring the matrix containing the medicine into a suppository mold, inserting the expansion carrier, and adhering and shaping to obtain the suppository;
(5) and (4) impregnating a regulator on the surface of the expansion carrier of the suppository in the step (4), and drying in vacuum to obtain the vaginal effervescent suppository.
Example 5
This example provides an effervescent vaginal suppository having the composition shown in table 3.
TABLE 3
Figure BDA0002267920670000131
The preparation method of the vaginal effervescent suppository comprises the following steps:
(1) mixing the emulsifier, the sustained release agent, the effervescent agent and the foaming agent in the formula ratio in a water bath to prepare an oil phase;
(2) slowly dripping a mixed solution containing tinidazole, daunomycin, acyclovir, an angelica sinensis extract and a cyclodextrin metal organic framework in a formula amount as a water phase into the oil phase in the step (1), and performing ultrasonic treatment, wherein the ultrasonic-assisted time is 30min, and the ultrasonic-assisted frequency is 40kHz to obtain a pre-emulsion, wherein the dripping speed is 10 mL/min;
(3) carrying out rapid membrane emulsification on the pre-emulsion obtained in the step (2), and passing through a microporous membrane with the aperture of 2 microns under the pressure of 0.8MPa to obtain a drug-containing matrix;
(4) pouring the matrix containing the medicine into a suppository mold, inserting the expansion carrier, and adhering and shaping to obtain the suppository;
(5) and (4) impregnating a regulator on the surface of the expansion carrier of the suppository in the step (4), and drying in vacuum to obtain the vaginal effervescent suppository.
Example 6
This example provides an effervescent vaginal suppository having the composition shown in table 4.
TABLE 4
Figure BDA0002267920670000141
The preparation method of the vaginal effervescent suppository comprises the following steps:
(1) mixing the emulsifier, the sustained release agent, the effervescent agent and the foaming agent in the formula ratio in a water bath to prepare an oil phase;
(2) slowly dripping a mixed solution containing amoxicillin, fluconazole, interferon, borneol extract and cyclodextrin metal organic framework with the formula amount as a water phase into the oil phase in the step (1), and carrying out ultrasonic treatment, wherein the ultrasonic-assisted time is 40min, the ultrasonic-assisted frequency is 60kHz, so as to obtain a pre-emulsion, and the dripping speed is 15 mL/min;
(3) carrying out rapid membrane emulsification on the pre-emulsion obtained in the step (2), and passing through a microporous membrane with the aperture of 1 mu m under the pressure of 1.2MPa to obtain a drug-containing matrix;
(4) pouring the matrix containing the medicine into a suppository mold, inserting the expansion carrier, and adhering and shaping to obtain the suppository;
(5) and (4) impregnating a regulator on the surface of the expansion carrier of the suppository in the step (4), and drying under vacuum to obtain the vaginal effervescent suppository.
Example 7
This example provides an effervescent vaginal suppository having the composition shown in table 5.
TABLE 5
Figure BDA0002267920670000151
The preparation method of the vaginal effervescent suppository comprises the following steps:
(1) mixing the emulsifier, the sustained release agent, the effervescent agent and the foaming agent in the formula ratio in a water bath to prepare an oil phase;
(2) slowly dripping a mixed solution containing lincomycin, itraconazole, interferon, an bighead atractylodes rhizome extract, an astragalus extract and a cyclodextrin metal organic framework in a formula amount as a water phase into the oil phase in the step (1), and performing ultrasonic treatment, wherein the ultrasonic-assisted time is 60min, and the ultrasonic-assisted frequency is 35kHz to obtain a pre-emulsion, and the dripping speed is 5 mL/min;
(3) carrying out rapid membrane emulsification on the pre-emulsion obtained in the step (2), and passing through a microporous membrane with the aperture of 3 mu m under the pressure of 1.5MPa to obtain a drug-containing matrix;
(4) pouring the matrix containing the medicine into a suppository mold, inserting the expansion carrier, and adhering and shaping to obtain the suppository;
(5) and (4) impregnating a regulator on the surface of the expansion carrier of the suppository in the step (4), and drying in vacuum to obtain the vaginal effervescent suppository.
Example 8
This example provides an effervescent vaginal suppository having the composition shown in table 6.
TABLE 6
Figure BDA0002267920670000161
Figure BDA0002267920670000171
The preparation method of the vaginal effervescent suppository comprises the following steps:
(1) mixing the emulsifier, the sustained release agent, the effervescent agent and the foaming agent in the formula ratio in a water bath to prepare an oil phase;
(2) slowly dripping a mixed solution containing ornidazole, amphotericin B, interferon, radix rehmanniae preparata extract and cyclodextrin metal-organic framework in a formula amount as a water phase into the oil phase in the step (1), and performing ultrasonic treatment, wherein the ultrasonic auxiliary time is 20min, and the ultrasonic auxiliary frequency is 80kHz, so as to obtain a pre-emulsion, wherein the dripping speed is 20 mL/min;
(3) carrying out rapid membrane emulsification on the pre-emulsion obtained in the step (2), and passing through a microporous membrane with the aperture of 0.5 mu m under the pressure of 0.5MPa to obtain a drug-containing matrix;
(4) pouring the matrix containing the medicine into a suppository mold, inserting the expansion carrier, and adhering and shaping to obtain the suppository;
(5) and (4) impregnating a regulator on the surface of the expansion carrier of the suppository in the step (4), and drying in vacuum to obtain the vaginal effervescent suppository.
Example 9
This example provides an effervescent vaginal suppository having the composition shown in table 7.
TABLE 7
Figure BDA0002267920670000172
The effervescent vaginal suppository was prepared in the same manner as in example 4.
Example 10
This example provides an effervescent vaginal suppository having the composition shown in table 8.
TABLE 8
Figure BDA0002267920670000182
The effervescent vaginal suppository was prepared in the same manner as in example 4.
Example 11
This example provides an effervescent vaginal suppository having the composition shown in table 9.
TABLE 9
Figure BDA0002267920670000183
Figure BDA0002267920670000191
The effervescent vaginal suppository was prepared in the same manner as in example 4.
Example 12
This example provides an effervescent vaginal suppository having the composition shown in table 10.
Watch 10
Figure BDA0002267920670000192
Figure BDA0002267920670000201
The effervescent vaginal suppository was prepared in the same manner as in example 4.
Example 13
This example provides an effervescent vaginal suppository having the composition shown in table 11.
TABLE 11
Figure BDA0002267920670000202
The effervescent vaginal suppository was prepared in the same manner as in example 4.
Example 14
This example provides an effervescent vaginal suppository having the composition shown in table 12.
TABLE 12
Figure BDA0002267920670000211
The effervescent vaginal suppository was prepared in the same manner as in example 4.
Example 15
The effervescent suppository provided in this example is the same as example 4 except that cyclodextrin metal organic framework is not added, the weight part of hydroxypropyl cellulose is 92 parts, and the weight part of sodium alginate is 23 parts, and the preparation method provided in this example is the same as example 4.
Example 16
The effervescent suppository provided by the embodiment is the same as the effervescent suppository provided by the embodiment 4 except that the weight part of methylparaben is 25, and the preparation method provided by the embodiment is the same as the effervescent suppository provided by the embodiment 4.
Example 17
The effervescent suppository provided by the embodiment is the same as the effervescent suppository provided by the embodiment 4 except that the weight part of methylparaben is 3, and the preparation method provided by the embodiment is the same as the effervescent suppository provided by the embodiment 4.
Example 18
The effervescent suppository provided by the embodiment is the same as the embodiment 4 except that the weight ratio of the acid component to the alkali component in the effervescent agent is 1:1, and the preparation method provided by the embodiment is the same as the embodiment 4.
Example 19
The effervescent suppository provided by the embodiment is the same as the embodiment 4 except that the weight ratio of the acid component to the alkali component in the effervescent agent is 10:1, and the preparation method provided by the embodiment is the same as the embodiment 4.
Comparative example 1
This comparative example provides a vaginal suppository that is the same as example 4 except that it does not include an effervescent agent, and is prepared in the same manner as example 4.
Comparative example 2
This comparative example provides a vaginal suppository that is the same as example 4 except that it does not include an expansion vehicle, and is prepared in the same manner as example 4.
II) clinical trials
The test method of the treatment effect is formulated according to the content of ' clinical verification of local drug administration of gynecological genital tract inflammation ' related to the clinical guidance principle of new drugs of Ministry of public health of the people's republic of China.
1. Test cases: 189 patients were admitted, 63 patients with bacterial vaginitis, 63 patients with fungal vaginitis and 63 patients with viral vaginitis, all aged 18-62 years, and patients in pregnancy and lactation period were excluded;
2. diagnostic criteria:
symptoms are: pruritus vulvae, burning pain, or frequent micturition, urgent micturition, and odynuria;
gynecological examination: the bacterial vaginitis has uniform and thin secretion substances and fishy smell; candidal vulvovaginal disease with more white bean dreg-like leucorrhea;
laboratory examination: the bacterial vaginitis can find clue cells, fungal vaginosis and smear detection in secretion under a microscope, false hyphae can be found under the microscope, and the positive rate can reach 60%;
3. grouping and administration: 63 cases of bacterial vaginosis were randomly divided into 57 cases of treatment groups and 6 cases of control groups; dividing 63 patients with mycotic vaginosis into 57 cases of treatment groups and 6 cases of control groups randomly; randomly dividing 63 cases of viral vaginitis into 57 cases of treatment groups and 6 cases of control groups; the above treatment groups were administered with the effervescent vaginal suppositories of examples 1-19, three per group, and the control group was administered with the vaginal suppositories of comparative examples 1-2, three per group, respectively;
4. observation items
The treatment results are as follows: the treatment effect is shown in table 13 after 4 courses of administration, where "-" indicates no treatment effect.
Watch 13
Figure BDA0002267920670000231
As can be seen from table 13, the vaginal effervescent suppository provided by embodiments 1 to 12 of the present invention can significantly and effectively improve the treatment effect of vaginitis, and the effective components in the vaginal effervescent suppository of embodiment 1 are antibacterial drugs, and the effective rate of treatment of bacterial vaginitis is as high as 95.8%; in the embodiment 2, the pharmacodynamic components in the vaginal effervescent suppository are antifungal drugs, and the effective rate of the vaginal effervescent suppository on the treatment of colpomycosis is as high as 95.9 percent; in example 3, the active ingredients in the vaginal effervescent suppository are antiviral drugs, and the effective rate of the vaginal effervescent suppository on viral vaginitis reaches 95.1 percent; in examples 4-12, the active ingredients of the vaginal effervescent suppository are antibacterial drugs, antifungal drugs and antiviral drugs, the effective rate of the vaginal effervescent suppository for treating bacterial vaginitis reaches 99.8%, the effective rate of the vaginal effervescent suppository for treating fungal vaginitis reaches 100%, and the effective rate of the vaginal effervescent suppository for treating bacterial vaginitis reaches 100%.
In example 13, the addition amount of the cyclodextrin metal-organic framework is small, the slow-release effect of the prepared vaginal effervescent suppository is poor, and the treatment effective rate of the prepared vaginal effervescent suppository on bacterial vaginitis is 95.5 percent and is lower than 99.8 percent in example 4; the effective rate of treating the colpomycosis is 95.9 percent and is lower than 100 percent of that in the example 4; the effective rate of the treatment for the viral vaginitis is 96.8 percent and is lower than 100 percent in example 4.
In example 14, the addition amount of the cyclodextrin metal-organic framework is large, the drug effect release of the prepared vaginal effervescent suppository is slow, and the treatment effective rate of the prepared vaginal effervescent suppository on bacterial vaginitis is 98.1 percent and is lower than 99.8 percent in example 4; the effective rate of treating the colpomycosis is 98.6 percent and is lower than 100 percent of that in the example 4; the effective rate of the treatment for the viral vaginitis is 97.9 percent and is lower than 100 percent in example 4.
In example 15, cyclodextrin metal organic frameworks are not added, the drug effect slow release effect of the prepared vaginal effervescent suppository is poor, and the treatment effective rate of the prepared vaginal effervescent suppository on bacterial vaginitis is 94.9 percent and is lower than 99.8 percent in example 4; the effective rate of treating the colpomycosis is 95.2 percent and is lower than 100 percent of that in the example 4; the effective rate of the treatment for the viral vaginitis is 96.1 percent and is lower than 100 percent in example 4.
In example 16, the addition amount of methylparaben is large, and the effective rate of the prepared vaginal effervescent suppository on bacterial vaginitis is 95.8 percent and is lower than 99.8 percent of that in example 4; the effective rate of treating the colpomycosis is 95.2 percent and is lower than 100 percent of that in the example 4; the effective rate of the treatment for the viral vaginitis is 98.7 percent and is lower than 100 percent in example 4.
In example 17, the addition amount of methylparaben is small, and the effective rate of the prepared vaginal effervescent suppository on bacterial vaginitis is 95.2 percent and is lower than 99.8 percent of that in example 4; the effective rate of treating the colpomycosis is 95.6 percent and is lower than 100 percent of that in the example 4; the effective rate of the treatment for the viral vaginitis is 95.8 percent and is lower than 100 percent in example 4.
The ratio of acid component to base component in examples 18-19 is beyond the range of the technical solutions provided in the present application. Wherein, the effective rate of the vaginal effervescent suppository prepared in the example 18 to the bacterial vaginitis is 93.8 percent and is lower than 99.8 percent of that in the example 4; the effective rate of treating the colpomycosis is 93.6 percent, which is lower than 100 percent of that in the example 4; the effective rate of the treatment for the viral vaginitis is 92.8 percent and is lower than 100 percent in example 4.
The effective rate of the vaginal effervescent suppository prepared in example 19 to the bacterial vaginitis is 91.1 percent and is lower than 99.8 percent of that in example 4; the effective rate of treating the colpomycosis is 90.8 percent, which is lower than 100 percent of that in the example 4; the effective rate of the treatment for the viral vaginitis is 91.6 percent and is lower than 100 percent in example 4.
The vaginal suppository provided by the comparative example 1 is not added with the effervescent agent, the rest is the same as that in the example 4, as the effervescent agent is not added, the drug effect component has slow drug effect, and the administration effect is poor, the cure rate to bacterial vaginitis is only 88.5%, the cure rate to fungal vaginitis is only 81.2%, and the cure rate to viral vaginitis is only 86.1%.
The pessary provided in comparative example 2 is not added with the swelling carrier, and the rest is the same as that of example 4, because the swelling carrier is not added, the duration of the drug effect is short, the administration effect is poor, the cure rate for bacterial vaginitis is only 85.3%, the cure rate for fungal vaginitis is only 87.6%, and the cure rate for viral vaginitis is only 86.3%.
Comparing example 1 with comparative examples 1-2, it can be seen that the addition of the effervescent agent and the swelling vehicle increases the contact area of the pharmaceutical ingredients with the intravaginal lesion, and improves the healing effect of the effervescent suppository on vaginitis.
In conclusion, the effervescent suppository provided by the invention expands the expansion carrier through the effervescent action, increases the contact area of the drug effect components in the suppository and the vagina, increases the administration area, improves the antibacterial and anti-inflammatory capabilities, has the effective rate of 99.8 percent for treating bacterial vaginitis, 100 percent for treating fungal vaginitis and 100 percent for treating bacterial vaginitis; the matrix of the effervescent suppository provided by the invention can prolong the release time of the medicinal components, improve the persistence of the medicinal effect, improve the medicinal effect within 4-6 hours to 12-16 hours and reduce the medicament replacement.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention, and are not intended to limit the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
The applicant declares that the above description is only a specific embodiment of the present invention, but the scope of the present invention is not limited thereto, and it should be understood by those skilled in the art that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are within the scope and disclosure of the present invention.

Claims (10)

1. The vaginal effervescent suppository is characterized by comprising the following components in parts by weight:
Figure FDA0002267920660000011
2. the effervescent vaginal suppository as claimed in claim 1, wherein the pharmacodynamic component comprises any one or a combination of at least two of antibacterial drugs, antifungal drugs, antiviral drugs or herbal extracts, preferably a combination of antibacterial drugs, antifungal drugs, antiviral drugs and herbal extracts;
preferably, the mass ratio of the antibacterial drug, the antifungal drug, the antiviral drug and the traditional Chinese medicine extract is (1-3): 1-3, preferably 1:1:1: 1;
preferably, the antibacterial drug comprises any one or a combination of at least two of nitroimidazole derivative drugs, penicillin drugs, cephalosporin drugs, aminoglycoside drugs, macrolide drugs, lincomycin drugs, quinolone drugs or chlorhexidine acetate, and is preferably nitroimidazole derivative drugs;
preferably, the nitroimidazole derivative drug comprises any one or a combination of at least two of metronidazole, secnidazole, ornidazole, metronidazole or tinidazole;
preferably, the antifungal drug comprises any one of flucytosine, amphotericin B, nystatin, globithromycin, meparicin, fluconazole, clotrimazole, econazole nitrate or itraconazole or a combination of at least two of the same;
preferably, the antiviral drug comprises any one or a combination of at least two of amantadine, acyclovir or interferon;
preferably, the raw materials of the traditional Chinese medicine extract comprise any one or a combination of at least two of radix sophorae flavescentis, cortex phellodendri, radix scutellariae, curcuma zedoary, clam shell powder, red lead, catechu, frankincense, myrrh, pig gall powder, rheum officinale, fructus cnidii, herba epimedii, radix dipsaci, spina gleditsiae, cassia twig, fructus aurantii, matrine, leonurus heterophyllus, prepared rehmannia root, angelica sinensis, radix paeoniae alba, rhizoma atractylodis macrocephalae, poria cocos, codonopsis pilosula, liquorice, donkey-hide gelatin, cinnamon, andrographis paniculata.
3. The effervescent vaginal suppository of claim 1 or 2, wherein the effervescent agent consists of an acid component and a base component;
preferably, the acid component comprises any one of tartaric acid, citric acid or potassium hydrogen tartrate or a combination of at least two thereof;
preferably, the base component comprises sodium bicarbonate and/or potassium bicarbonate;
preferably, the mass ratio of the acid component to the base component is (3-8):1, preferably (4-6): 1.
4. The effervescent vaginal suppository of any one of claims 1-3, further comprising a foaming agent;
preferably, the foaming agent is 1-5 parts by weight, preferably 2-4 parts by weight;
preferably, the foaming agent comprises any one of or a combination of at least two of tween 20, tween 60, tween 80, sodium dodecyl sulfate and linear sodium dodecyl benzene sulfonate, preferably a combination of tween 60 and sodium dodecyl sulfate.
5. The effervescent vaginal suppository of any one of claims 1-4, wherein the matrix comprises a water soluble matrix;
preferably, the water-soluble matrix comprises any one or a combination of at least two of glycerol gelatin, polyethylene glycol 400, polyethylene glycol 1000 and polyethylene glycol 4000, preferably the combination of the glycerol gelatin and the polyethylene glycol 4000;
preferably, the mass ratio of the glycerogelatin to the polyethylene glycol 4000 is (1-5) to 1, preferably (2-4) to 1;
preferably, a cyclodextrin metal organic framework is also added into the matrix;
preferably, the mass ratio of the cyclodextrin metal-organic framework to the polyethylene glycol 4000 is (1-2):1, preferably 1.6: 1;
preferably, the matrix is also added with methyl hydroxybenzoate;
preferably, the mass ratio of the methyl hydroxybenzoate to the polyethylene glycol 4000 is 1 (5-10), preferably 1 (6-8).
6. The effervescent vaginal suppository of any one of claims 1-5, wherein an emulsifier and/or a corrosion inhibitor is further added to the matrix;
preferably, the weight portion of the emulsifier is 12-16, preferably 13-15;
preferably, the weight portion of the corrosion inhibitor is 32-48 parts, preferably 36-42 parts;
preferably, the emulsifier comprises any one or a combination of at least two of stearic acid, aluminum stearate or magnesium stearate, preferably a combination of stearic acid and magnesium stearate;
preferably, the weight ratio of stearic acid to magnesium stearate is (1-3) to 1, preferably 2: 1;
preferably, the sustained release agent comprises any one or a mixture of at least two of hydroxypropyl cellulose, sodium alginate, locust bean gum or lauryl alcohol, preferably the combination of hydroxypropyl cellulose and sodium alginate;
preferably, the weight ratio of the hydroxypropyl cellulose to the sodium alginate is (2-6):1, preferably (3-5): 1.
7. The effervescent vaginal suppository of any one of claims 1-6, wherein the expandable carrier comprises any one or a combination of at least two of a tampon, a non-woven fabric, or an elastic fiber, preferably a tampon;
preferably, the surface of the expanded carrier is coated with a conditioning agent;
preferably, the weight portion of the regulator is 5-20 parts, preferably 8-15 parts;
preferably, the regulator comprises any one or combination of at least two of hydroxymethyl cellulose, metformin or sodium alginate, preferably the combination of hydroxymethyl cellulose, metformin and sodium alginate;
preferably, the weight ratio of the hydroxymethyl cellulose to the metformin to the sodium alginate is (4-8): (2-4):1, preferably 6:3: 1.
8. A process for the preparation of effervescent vaginal suppository as claimed in any one of claims 1 to 7, characterized in that it comprises the following steps:
(1) mixing the emulsifier, the sustained release agent, the effervescent agent and the foaming agent in the formula ratio in a water bath to prepare an oil phase;
(2) dispersing a mixed solution containing antibacterial drugs, antifungal drugs, antiviral drugs, traditional Chinese medicine extracts and cyclodextrin metal organic frameworks in a formula ratio as a water phase in the oil phase in the step (1) to obtain a pre-emulsion;
(3) carrying out rapid membrane emulsification on the pre-emulsion obtained in the step (2), and passing through a microporous membrane to obtain a drug-containing matrix;
(4) pouring the matrix containing the medicine into a suppository mold, inserting the expansion carrier, and adhering and shaping to obtain the suppository;
(5) and (4) coating and/or impregnating a regulator on the surface of the expansion carrier of the suppository, and drying to obtain the vaginal effervescent suppository.
9. The method of claim 8, wherein the dispersing in step (2) is carried out by slowly adding the aqueous phase dropwise into the oil phase;
preferably, the speed of slowly dripping is 5-20mL/min, preferably 10-15 mL/min;
preferably, the dispersion is also accompanied by ultrasound assistance;
preferably, the ultrasound-assisted time is 20min to 60min, preferably 30 to 40 min;
preferably, the frequency of the ultrasonic assistance is 25-80kHz, preferably 40-60 kHz;
preferably, the pressure of the microporous membrane in the step (3) is 0.5-1.5MPa, preferably 0.8-1.2 MPa;
preferably, the pore size of the microporous membrane is 0.5-3 μm, preferably 1-2 μm;
preferably, the drying of step (5) is vacuum drying.
10. Use of an effervescent vaginal suppository as claimed in any one of claims 1 to 9 for the preparation of a medicament and/or an agent for the treatment of vaginitis.
CN201911094603.1A 2019-11-11 2019-11-11 Vaginal effervescent suppository and preparation method and application thereof Pending CN110638744A (en)

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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
CN114452315A (en) * 2022-03-16 2022-05-10 郑州大学第一附属医院 Vaginal effervescent suppository and preparation method thereof
CN115837046A (en) * 2022-11-23 2023-03-24 哈尔滨誉衡制药有限公司 Ornidazole pessary and preparation method thereof

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CN108310364A (en) * 2018-04-26 2018-07-24 霍尔果斯汉智医药科技有限公司 A kind of amphotericin B vaginal expansion plug and preparation method thereof
CN108324932A (en) * 2018-04-26 2018-07-27 霍尔果斯汉智医药科技有限公司 A kind of lactoferrin vaginal expansion plug and preparation method thereof

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CN108310364A (en) * 2018-04-26 2018-07-24 霍尔果斯汉智医药科技有限公司 A kind of amphotericin B vaginal expansion plug and preparation method thereof
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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
CN113694036B (en) * 2021-09-18 2023-08-22 华北制药股份有限公司 Amphotericin B vaginal effervescent tablet and preparation method thereof
CN114452315A (en) * 2022-03-16 2022-05-10 郑州大学第一附属医院 Vaginal effervescent suppository and preparation method thereof
CN115837046A (en) * 2022-11-23 2023-03-24 哈尔滨誉衡制药有限公司 Ornidazole pessary and preparation method thereof

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