CN117582437A - Application of compound in preparing vaginal topical preparation for treating colpitis - Google Patents
Application of compound in preparing vaginal topical preparation for treating colpitis Download PDFInfo
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- CN117582437A CN117582437A CN202311472858.3A CN202311472858A CN117582437A CN 117582437 A CN117582437 A CN 117582437A CN 202311472858 A CN202311472858 A CN 202311472858A CN 117582437 A CN117582437 A CN 117582437A
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- Prior art keywords
- compound
- use according
- vaginal
- vaginitis
- formulation
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 201000005882 tinea unguium Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000000003 vaginal tablet Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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Abstract
The invention provides application of a compound in preparing a vaginal local administration preparation for treating colpitis, wherein the compound is a compound with the following structural formula or physiologically acceptable salt thereof:in the structural formula, R 1 And R is 2 Respectively H or F, R 3 Is a heterocycle. The invention provides a compound with strong antifungal activity, which can promote the recovery of the vaginal microbial ecosystem, provides a strategy for solving the problems of poor efficacy and more drug resistance of most of the prior anti-candida drugs, and provides a vaginaThe formulation of the topical formulation provides a more effective option for patients with mycotic vaginitis.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of a compound in preparing a vaginal local administration preparation for treating colpitis.
Background
Abnormal vaginal secretions, malodor, vaginal itching, burning, and even pain, collectively referred to as vaginitis. Associated with microbial infections, mainly bacteria, fungi (candida) and trichomonas. Vaginal dysbacteriosis, reduced hormone levels, pregnancy, diabetes, unclean custom, immune damage, etc. are susceptibility factors that induce vaginitis. Vaginitis caused by bacterial infection is called bacterial vaginitis (BV for short), and vaginitis caused by fungal infection is called mycotic vaginitis. Since the vast majority of colpitis mycotica is caused by candida infection, it is also known as candidal vaginitis (VVC for short). Of the vaginal candida family, about 90% are candida albicans.
About 70-75% of women will be infected with candida at least once throughout their lives, with pregnant women having an infection rate of about 20% and immunocompromisers about 30%. Female patients who take antibiotics orally for a long period of time may also develop secondary VVC. In one year, patients infected more than 4 times are called recurrent mycotic vaginitis, and the incidence rate is about 8%.
The current treatment of VVC is mainly treatment with antifungal agents such as fluconazole, miconazole, clotrimazole, nystatin, etc., which are used for a longer period of time, most of which have poor anti-candida efficacy and more resistance. Voriconazole, fosravuconazoles and Isavuconazonium sulfate are new antifungal drugs marketed in recent years, and are all oral preparations although they have a strong effect against candida albicans. After the oral preparation is taken, the active ingredients firstly enter blood and are transported to the vaginal infection part through blood circulation, the transportation path of the medicine in the body is long, and the medicine is easy to be metabolized by liver and kidney or degraded by digestive juice, so that the medicine is damaged, and the treatment dosage is required to be increased. During the transport process, the drug may also be absorbed by other organs and tissues, resulting in toxic side effects and drug interactions. Oral medications have a relatively long period of time to eliminate and may also adversely affect recovery of the vaginal microbial flora. In addition, gestational VVC patients cannot be administered orally. VVC is a superficial infection of mucous membrane, and the ideal treatment mode is vaginal administration, the medicine is in direct contact with pathogenic bacteria, contact and kill, the medicine does not enter or seldom enter blood, and has no or little influence on the systemic system and low toxic and side effects.
Although literature reports that ifetrozole, lei Fukang azole and isaconazole have strong inhibitory effects on candida, particularly candida albicans, ifetrozole is mainly used for preparing medicines for treating onychomycosis, lei Fukang azole and isaconazole are mainly used as intermediates for preparing fosravuconazoles and Isavuconazonium sulfate, no literature reports that the compounds are directly used as active ingredients, and vaginal topical administration preparations for treating VVC are developed or produced.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides application of a compound in preparing a vaginal local administration preparation for treating colpitis.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the invention provides application of a compound in preparing a vaginal local administration preparation for treating colpitis, wherein the compound is shown in a structural formula I or physiologically acceptable salt thereof:
in formula I, R 1 And R is 2 Respectively H or F, R 3 Is a heterocycle.
Further, the above compound is efaconazole (Efinacon azole), R 1 Is H, R 2 Is F, R 3 Is that
Further, the above compound is Lei Fukang azole (Ravuconazole), R 1 Is H, R 2 Is F, R 3 Is that
Further, the compound is isavuconazol (Isavauconazole), R 1 Is F, R 2 Is H, R 3 Is that
Further, the amount of the compound represented by the structural formula I or a physiologically acceptable salt thereof per unit of the preparation is 10 to 300mg, preferably 20 to 200mg, per unit of the preparation.
Further, the dosage form of the vaginal topical administration preparation is suppository, tablet, soft capsule, cream, gel, cream or spray.
Further, the suppositories, ointments, gels and creams described above also include a controlled release material and a matrix.
Further, the tablet further comprises a controlled release material, a binder and a lubricant.
Further, the spray further comprises a controlled release material and a solvent.
In one step, the controlled release material is maltodextrin.
Further, the controlled release material may further comprise one or more of chitosan, modified chitosan, acacia, xanthan gum, tragacanth, guar gum, povidone, carboxymethylcellulose, hydroxypropyl methylcellulose, poloxamer, carbomer, and polycarbophil in addition to maltodextrin.
Further, the matrix includes an oil-soluble matrix and/or a water-soluble matrix; the oil-soluble matrix is preferably selected from one or more of cocoa butter, hydrogenated neutral fat, mixed fatty acid glyceride, propylene glycol stearate; the water-soluble matrix is preferably one or more selected from glycerogelatin, polyethylene glycol, poloxamer, polyoxyethylene stearate, polyoxyethylene sorbitan monostearate.
Further, the above suppositories may optionally contain a plasticizer, preferably one or more selected from the group consisting of polysorbates, fatty acid glycerides, castor oil.
Further, the binder is one or more selected from acacia, starch, povidone, hydroxypropyl cellulose and hydroxyethyl cellulose, preferably including povidone and starch.
Further, the lubricant is one or more selected from stearate, talcum powder, silica gel micropowder, hydrogenated vegetable oil, polyethylene glycol and sodium dodecyl sulfate, preferably one or more selected from magnesium stearate, talcum powder and silica gel micropowder.
Further, the tablet may further comprise a filler, if necessary, preferably one or more selected from starch, modified starch, microcrystalline cellulose and mannitol.
Further, the solvent in the spray preparation is one or more selected from water, ethylene glycol, propylene glycol, glycerol, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, polyethylene glycol and polyethylene glycol modified substances; the amount of the above-mentioned compounds in the solvent is 0.01 to 10w/v%, preferably 0.1 to 2w/v%.
Further, the vaginitis is mycotic vaginitis, preferably mycotic vaginitis.
Compared with the prior art, the invention has the following technical effects:
the invention provides a compound with strong antifungal activity, which can promote the recovery of the vaginal microbial ecosystem, provides a strategy for solving the problems of poor efficacy and more drug resistance of most of the prior anti-candida drugs, and provides a formulation of a vaginal local administration preparation, thereby providing more effective selection for patients with mycotic vaginitis.
Detailed Description
The invention provides application of a compound in preparing a vaginal local administration preparation for treating colpitis, wherein the compound is shown in a structural formula I or physiologically acceptable salt thereof:
in formula I, R 1 And R is 2 Respectively H or F, R 3 Is a heterocycle.
In a preferred embodiment of the present invention, the compound is efaconazole (Efinacon azole), R 1 Is H, R 2 Is F, R 3 Is that
In a preferred embodiment of the present invention, the compound is Lei Fukang azole (Ravuconazole), R 1 Is H, R 2 Is F, R 3 Is that
In a preferred embodiment of the present invention, the compound is Isavuconazole (Isavauconazole), R 1 Is F, R 2 Is H, R 3 Is that
In a preferred embodiment of the present invention, the dosage of the preparation for vaginal topical administration is in the form of a preparation unit containing the compound of formula I or a physiologically acceptable salt thereof in an amount of 10 to 300mg, preferably 20 to 200mg per preparation unit.
In a preferred embodiment of the present invention, the formulation of the above-mentioned preparation for topical vaginal administration is a suppository, tablet, soft capsule, cream, gel, cream or spray.
In a preferred embodiment of the present invention, the above-mentioned vaginal topical preparation preferably contains a drug release controlling material. The controlled release material adopted by the invention mainly plays a role in controlling the slow running time and the drug release speed of the drug in the vagina.
In a preferred embodiment of the invention, the controlled release material is preferably maltodextrin. The amount of maltodextrin is preferably 5 to 100mg, preferably 10 to 60mg, per unit dosage of maltodextrin per unit dosage of the preparation for vaginal topical administration.
In a preferred embodiment of the present invention, the controlled release material may comprise one or more of chitosan, modified chitosan, acacia, xanthan gum, tragacanth gum, guar gum, povidone, carboxymethylcellulose, hydroxypropyl methylcellulose, poloxamer, carbomer, polycarbophil, in addition to maltodextrin. The content of the controlled release material in the formulation unit is 0.5 to 20%, preferably 1 to 10%.
In a preferred embodiment of the present invention, the suppository further comprises a controlled release material and a matrix, and if necessary, a plasticizer.
In a preferred embodiment of the present invention, the above tablet further comprises a controlled release material, a binder and a lubricant, and if necessary, a filler.
In a preferred embodiment of the present invention, the matrix comprises an oil-soluble matrix and/or a water-soluble matrix; the oil-soluble matrix is preferably selected from one or more of cocoa butter, hydrogenated neutral fat, mixed fatty acid glyceride, propylene glycol stearate; the water-soluble matrix is preferably one or more selected from glycerogelatin, polyethylene glycol, poloxamer, polyoxyethylene stearate, polyoxyethylene sorbitan monostearate. The matrix may be one substance or a mixture of two or more substances. The matrix is present in the formulation unit in an amount of 60-99%, preferably 70-95%, most preferably 80-95%.
The plasticizer adopted by the invention mainly aims at reducing the brittleness of the medicine, increasing the elasticity of the suppository of the medicine and preventing the medicine from cracking, and is added according to the requirement. In a preferred embodiment of the invention, the plasticizer is selected from one or more of polysorbate, fatty acid glyceride, castor oil. The plasticizer content in the formulation unit is 0.5-20%, preferably 1-10%.
In the present invention, the binder is a reagent for binding the formulation materials in the pharmaceutical agent together to prepare a molded product. In a preferred embodiment of the invention, the binder is selected from one or more of acacia, starch, povidone, hydroxypropyl cellulose, hydroxyethyl cellulose, preferably including povidone and starch. The binder content in the preparation unit is 0.1-10%, preferably 0.2-7%.
The lubricant of the invention is a substance which reduces the friction force between the tablet and the die in the tabletting process, prevents raw and auxiliary materials from adhering to the surface of the punch and protects the integrity of the tablet. In a preferred embodiment of the present invention, the lubricant is one or more selected from the group consisting of stearate, talc, silica fume, hydrogenated vegetable oil, polyethylene glycol, and sodium dodecyl sulfate, and preferably one or more selected from the group consisting of magnesium stearate, talc, and silica fume. The lubricant is present in the formulation unit in an amount of 0.1 to 10%, preferably 0.2 to 5%.
In the present invention, the filler is mainly added as needed to adjust the size and weight of the tablet. In a preferred embodiment of the invention, the filler material is selected from one or more of starch, modified starch, microcrystalline cellulose, mannitol.
The spray is prepared by dissolving or suspending the drug in a solvent to form a solution or emulsion or suspension, and then spraying the content with a sprayer. In a preferred embodiment of the present invention, the solvent in the spray formulation is selected from one or more of water, ethylene glycol, propylene glycol, glycerin, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, polyethylene glycol modifications; the amount of the above-mentioned compounds in the solution or suspension is 0.01 to 10w/v%, preferably 0.1 to 2w/v%.
In a preferred embodiment of the invention, the creams, gels and creams described above further comprise a controlled release material, a matrix, preferably a maltodextrin-containing matrix.
In a preferred embodiment of the invention, the vaginitis is a fungal vaginitis, preferably a fungal vaginitis.
The present invention will be described in detail and in detail by way of the following examples, which are not intended to limit the scope of the invention, for better understanding of the invention.
The method in the examples adopts a conventional method without special description, and the used auxiliary materials are the mixture of the conventional commercial auxiliary materials or the auxiliary materials prepared by the conventional method without special description.
Example 1
The present example demonstrates the antifungal effects of ifetrozole, lei Fukang azole and isaconazole, with the following experimental steps and results:
the Minimum Inhibitory Concentrations (MIC) (μg/mL) of the efucazone, lei Fukang azole, isaconazole, clotrimazole, voriconazole, posaconazole, itraconazole and fluconazole were determined by taking 20 strains of clinical isolates of candida albicans, candida glabrata, candida tropicalis and candida parapsilosis respectively, performing a drug-sensitive experiment with reference to the American CLSIM38-A3 liquid microdilution method, and comparing the antibacterial activities as shown in Table 1 below.
TABLE 1 MIC (μg/mL) of several antifungal agents for inhibiting Candida vaginalis
From the above table, it can be seen that the inhibition effect of ifetrozole, lei Fukang azole and isaconazole on candida is significantly better than other antifungal agents.
Example 2
The present example adopts an animal in vivo model to verify the superiority of ifetroconazole relative to miconazole in the treatment of vaginal candida infection, and the specific experimental steps and results are as follows:
1. sample preparation
Samples 1-3 were prepared according to the formulation of table 2 below.
TABLE 2 preparation of samples 1-3 formulation (1000 particles)
Mixing the efucazol or miconazole, the mixed fatty glyceride (36 type), the cyclodextrin or the maltodextrin and the lactic acid, heating and melting, putting into a mould, and cooling and forming. Making into suppository with weight of 40 mg.
2. Pharmacological test
Five week old mice (18 g in weight) were randomized into four groups of 5 animals placed in the same cage. Food and water were provided ad libitum.
Mice were subcutaneously injected with 0.5mg of estradiol valerate three days before infection and 4, 11 and 18 days after challenge, with false oestrus maintained throughout the experiment. On the day of infection, ketamine hydrochloride (80 mg/kg) was administered intraperitoneally for anesthesia and intravaginal inoculation clinical isolation20. Mu.l 2X 10 Candida albicans of (A) 8 Colony Forming Units (CFU)/ml. The next day after inoculation, the swab smear was performed on the vagina of each mouse (prior to treatment), ensuring that all animals were infected. Thereafter, vaginal test samples were taken every 12 hours, and potassium hydroxide smear examination was performed to evaluate the therapeutic efficacy and recovery of vaginal microbial flora. The dosing was started the next day after infection, with the first and second groups being treatment groups given sample 1 and sample 2, respectively, the third group being positive control group given sample 3, the fourth group being negative control group given matrix-only mixed fatty acid glycerides, all placed in the posterior fornix.
The negative transfer times for each group of animal test smears are shown in Table 3.
TABLE 3 time to negative for each group of animal test strip smears
| Animal number | 1 | 2 | 3 | 4 | 5 | Average of |
| First group of | 36 | 48 | 48 | 60 | 60 | 50.4 |
| Second group of | 48 | 48 | 60 | 60 | 72 | 57.6 |
| Third group of | 60 | 72 | 72 | 72 | 84 | 72 |
| Fourth group | 72 | / | / | / | / |
From the results of the above table, it can be seen that:
(1) All animal test smears of the first group, the second group and the third group can turn negative, which shows that the efroconazole and the miconazole have curative effects on vaginal candida infection.
(2) The first group and the second group have obviously shorter negative-turning time than the third group, which shows that the curative effect of the ifetrozole on treating the candida vaginalis is better than that of the miconazole
(3) The first group had a shorter negative time than the second group, indicating that maltodextrin helped to enhance the efficacy of the drug.
Examples 3-6 Lei Fukang preparation of Axaconazole vaginal tablets
This example provides a tablet for the treatment of colpitis mycotica with the formulation shown in table 4 below.
Table 4 formulation of tablets for treating colpitis mycotica (mg)
The preparation process of the tablet comprises the following steps:
according to the amount shown in Table 4, lei Fukang azole or isaconazole, corn starch and maltodextrin are placed in a wet granulator and stirred and mixed, polyethylene glycol 6000 is dissolved in 15ml of water, sprayed into the granulator, sheared and granulated and dried. Granulating, mixing with pulvis Talci and magnesium stearate, and making into spindle-shaped tablet with long axis of 10mm, with average tablet weight of 330mg.
Example 7
This example provides a suppository for treating colpitis mycotica with the formulation shown in table 5 below.
Table 5 formulation of suppositories for the treatment of colpitis mycotica
| Material name | Feeding quantity (mg) |
| Efluorconazole | 50 |
| Hydrogenated neutral grease | 1930 |
| Maltodextrin | 10 |
| Poloxamer (poloxamer) | 10 |
| Total amount of | 2000 |
The preparation process of the suppository comprises the following steps:
mixing the efroconazole, the hydrogenated neutral oil ester, the maltodextrin and the poloxamer, heating and melting, putting into a mould, and cooling and forming. Making into suppository with average weight of 2000mg per granule.
Example 8
This example provides a suppository for treating colpitis mycotica with the formulation shown in table 6 below.
Table 6 formulation of suppositories for the treatment of mycotic vaginitis
| Material name | Feeding quantity (mg) |
| Esaconazole | 50 |
| Mixed fatty acid glyceride (36 type) | 1935 |
| Maltodextrin | 5 |
| Povidone k30 | 10 |
| Total amount of | 2000 |
The preparation process of the suppository comprises the following steps:
mixing isaconazole, mixed fatty glyceride (36 type), maltodextrin and povidone K30, heating and melting, putting into mould, cooling and shaping. Making into suppository with average weight of 2000mg per granule.
Example 9
This example provides a suppository for treating colpitis mycotica with the formulation shown in table 7 below.
Table 7 formulation of suppositories for the treatment of colpitis mycotica
| Material name | Feeding quantity (mg) |
| Lei Fukang Azole | 100 |
| PEG6000 | 1680 |
| Polyoxyethylene stearate | 200 |
| Maltodextrin | 10 |
| Hydroxypropyl methylcellulose | 10 |
| Total amount of | 2000 |
The preparation process of the suppository comprises the following steps:
mixing Lei Fukang oxazole, PEG6000, polyoxyethylene stearate, maltodextrin and hydroxypropyl methylcellulose, heating to melt, putting into mould, cooling and shaping. Making into suppository with average weight of 2000mg per granule.
Example 10
This example provides a suppository for treating colpitis mycotica with the formulation shown in table 8 below.
Table 8 formulation of suppositories for the treatment of mycotic vaginitis
The preparation process of the suppository comprises the following steps:
mixing the efroconazole, the PEG6000, the polyoxyethylene stearate, the maltodextrin and the chitosan, heating and melting, putting into a mould, and cooling and forming. Making into suppository with average weight of 1500mg per granule.
Example 11
This example provides a spray for the treatment of colpitis mycotica with the formulation shown in table 9 below.
Table 9 formulation of spray for treating colpitis mycotica
| Material name | Feeding quantity (mg) |
| Esaconazole | 20 |
| Lactic acid | 10 |
| Propylene glycol | 70 |
| Tetrahydrofuran polyethylene glycol | 50 |
| Caprylic capric polyethylene glycol glyceride | 35 |
| Maltodextrin | 5 |
| Benzyl alcohol | 10 |
| Total amount of | 200 |
The preparation process of the spray comprises the following steps:
mixing propylene glycol, tetrahydrofuran polyethylene glycol, caprylic/capric polyethylene glycol ester and benzyl alcohol according to the prescription, stirring, adding maltodextrin and isaconazole, heating for dissolving, cooling, adding lactic acid, stirring uniformly, and filling.
Example 12
This example provides a spray for the treatment of colpitis mycotica with the formulation shown in table 10 below.
Table 10 formulation of spray for treating colpitis mycotica
The preparation process of the spray comprises the following steps:
mixing PEG400, diethyl ether, tetrahydrofuran polyethylene glycol and benzyl alcohol according to the prescription, stirring, adding maltodextrin and efroconazole, heating for dissolving, cooling, adding lactic acid, stirring uniformly, and filling.
Example 13
This example provides a spray for the treatment of colpitis mycotica with the formulation shown in table 11 below.
Table 11 formulation of spray for treating colpitis mycotica
| Material name | Feeding quantity (mg) |
| Lei Fukang Azole | 100 |
| Lactic acid | 10 |
| PEG400 | 120 |
| Di (ethylene glycol) monoethyl ether | 80 |
| Tetrahydrofuran polyethylene glycol | 80 |
| Benzyl alcohol | 2 |
| Maltodextrin | 8 |
| Total amount of | 400 |
The preparation process of the spray comprises the following steps:
mixing PEG400, diethyl ether, tetrahydrofuran polyethylene glycol and benzyl alcohol according to the prescription, stirring, adding maltodextrin and Lei Fukang azole, heating for dissolving, cooling, adding lactic acid, stirring uniformly, and packaging.
The above description of the specific embodiments of the present invention has been given by way of example only, and the present invention is not limited to the above described specific embodiments. It will be apparent to those skilled in the art that any equivalent modifications and substitutions of the present invention are intended to be within the scope of the present invention. Accordingly, equivalent changes and modifications are intended to be included within the scope of the present invention without departing from the spirit and scope thereof.
Claims (15)
1. Use of a compound for the preparation of a formulation for topical vaginal administration for the treatment of vaginitis, wherein the compound is a compound of formula I:
in formula I, R 1 And R is 2 Respectively H or F, R 3 Is a heterocycle.
2. The use according to claim 1, wherein the compound is efroconazole, R 1 Is H, R 2 Is F, R 3 Is that
3. The use according to claim 1, wherein the compound is Lei Fukang azole, R 1 Is H, R 2 Is F, R 3 Is that
4. The use according to claim 1, wherein the compound is isaconazole, R 1 Is F, R 2 Is H, R 3 Is that
5. Use according to claim 1, wherein the dosage of the preparation for vaginal topical administration is in the form of a preparation unit containing the compound of formula I or a physiologically acceptable salt thereof in an amount of 10-300mg, preferably 20-200mg per preparation unit.
6. The use according to claim 1, wherein the formulation for vaginal topical administration is in the form of a suppository, tablet, soft capsule, cream, gel, cream or spray.
7. The use of claim 6, wherein the suppositories, ointments, gels, and creams further comprise a controlled release material and a matrix.
8. The use of claim 6, wherein the tablet further comprises a controlled release material, a binder, and a lubricant.
9. The use of claim 6, wherein the spray further comprises a controlled release material and a solvent.
10. The use according to any one of claims 7-9, wherein the controlled release material comprises maltodextrin, and further comprises one or more of chitosan, modified chitosan, acacia, xanthan gum, tragacanth, guar gum, povidone, carboxymethylcellulose, hydroxypropyl methylcellulose, poloxamer, carbomer, polycarbophil.
11. The use according to claim 7, wherein the matrix comprises an oil-soluble matrix and/or a water-soluble matrix; the oil-soluble matrix is preferably selected from one or more of cocoa butter, hydrogenated neutral fat, mixed fatty acid glyceride, propylene glycol stearate; the water-soluble matrix is preferably selected from one or more of glycerogelatin, polyethylene glycol, poloxamer, polyoxyethylene stearate, polyoxyethylene sorbitan monostearate.
12. Use according to claim 8, wherein the binder is selected from one or more of acacia, starch, povidone, hydroxypropyl cellulose, hydroxyethyl cellulose, preferably comprising povidone and starch.
13. The use according to claim 8, wherein the lubricant is selected from one or more of stearates, talc, aerosil, hydrogenated vegetable oil, polyethylene glycol, sodium dodecyl sulfate, preferably from one or more of magnesium stearate, talc and aerosil.
14. The use according to claim 9, wherein the solvent is selected from one or more of water, ethylene glycol, propylene glycol, glycerol, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, polyethylene glycol modifications; the amount of the compound in the solvent is 0.01 to 10w/v%, preferably 0.1 to 2w/v%.
15. Use according to claim 1, wherein the vaginitis is a fungal vaginitis, preferably a fungal vaginitis.
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|---|---|
| CN (1) | CN117582437A (en) |
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2023
- 2023-11-07 CN CN202311472858.3A patent/CN117582437A/en active Pending
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