CN108186553A - A kind of long-acting suppository of progesterone and preparation method thereof - Google Patents
A kind of long-acting suppository of progesterone and preparation method thereof Download PDFInfo
- Publication number
- CN108186553A CN108186553A CN201810148692.2A CN201810148692A CN108186553A CN 108186553 A CN108186553 A CN 108186553A CN 201810148692 A CN201810148692 A CN 201810148692A CN 108186553 A CN108186553 A CN 108186553A
- Authority
- CN
- China
- Prior art keywords
- suppository
- progesterone
- long
- acting
- binder
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
- A61K47/06—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
-
- 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
- A61K47/06—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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
-
- 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
- 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
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of long-acting suppositorys of progesterone, are mainly made of following weight percent composition：1~6% progesterone, 2~5% binders, 89~97% suppository bases.The present invention also provides the preparation methods of the long-acting suppository of above-mentioned progesterone.The long-acting suppository irritation of the progesterone is small, adhesion is strong, the residence time is long, leakage rate is small, drug release is slow.
Description
Technical field
The present invention relates to a kind of progesterone suppository more particularly to a kind of long-acting suppositorys of progesterone.While the invention further relates to
The preparation method of the long-acting suppository of the progesterone.
Background technology
Progesterone (Progesterone, P) also known as progesterone, gestogen, pregnendione, are mainly secreted, also by corpus luteum
It can be generated by the Deiter's cells of placenta and adrenal gland, testis and central nervous system.Progesterone is by corpus luteum
With a kind of natural progestogen of placenta secretion, there are notable Morphology Effects to the endometrium that estrogen excited in vivo, be
It maintains gestation institute required, is the most important sex hormone drug of Luteal phase support.Research shows that the progestational hormone of certain level is to gestation
Maintenance it is most important, gestation cuts off corpus luteum before 7 weeks can cause to miscarry, and the supplement of exogenous progestational hormone can enable gestation to tie up
It holds.Clinically for treating various diseases, such as menstrual disorder caused by corpus luteum is not complete, amenorrhoea and dysfunctional uterine go out progesterone
Blood, inadequate luteal function, threatened abortion and habitual abortion (because of lack of corpus luteum causer), premenstrual tension syndrome, postpartum
The Luteal phase support of depression etc. and assisted reproductive therapy (ART).
At present, the progesterone preparation listed has parenteral solution, capsule, soft capsule, suppository, vagina slowly-releasing gel, vagina
Piece and intrauterine contraception system etc..A large amount of clinical researches show that progesterone is taken orally with liver first-pass effect, bioavilability
It is low, toxic side effect is easily caused when dosage is larger；Progesterone drug administration by injection is curative for effect, but irritation is big during injection, causes patient
Pain and discomfort are used for a long time so that patient's medication compliance is low；Vagina administration and drug administration by injection therapeutic equivalence, medication compliance
Height, in ART Luteal phase supports, vaginal local delivery is the administration route of currently the only alternative intramuscular injection.Common vagina
With preparation, most of to select single water-soluble base or fatty matrix, drug release is very fast, and without adhesion, Yi Shouyin
The effect of function is removed in road itself, is excreted quickly, thus drug is short in the vaginal retention time, and leakage rate is big, has caused
Imitating dosage reduces, and effective time is short, influences the effect of drug therapy.
Therefore, the delay of research and development vagina length, slow release, cost-effective progesterone long-acting dosage form have faces well
Bed application prospect.
Invention content
First purpose of the present invention is to provide that a kind of irritation is small, adhesion is strong, the residence time is long, leakage rate is small and medicine
Object discharges the long-acting suppository of progesterone of slow vagina.
Second object of the present invention is to provide the preparation method of the long-acting suppository of above-mentioned progesterone.
In order to realize above-mentioned first purpose, technical solution provided by the invention is such：A kind of long-acting bolt of progesterone
Agent, including following weight percent composition：
Progesterone 1~6%；
Binder 2~5%；
Suppository base 89~97%.
Wherein, the progesterone uses the corpus luteum micropowder of grain diameter≤75 μm.
Wherein, the binder for Polycarbophil, carbomer, hydroxypropyl methylcellulose, chitosan, sodium carboxymethylcellulose,
Polyvinylpyrrolidone, Sodium Hyaluronate, sodium alginate, guar gum, xanthans and pectin one or more.
Preferably, binder and matrix type binder combination of the binder for strong adhesion, the strong adhesion
Binder is one or both of Polycarbophil and carbomer, and matrix type binder is hydroxypropyl methylcellulose, chitosan, carboxylic first
Base sodium cellulosate, polyvinylpyrrolidone, Sodium Hyaluronate, sodium alginate, guar gum, xanthans and pectin one or two
More than.
The binder of the strong adhesion and the mass fraction of matrix type binder are respectively：
The binder 10~40% of strong adhesion
Matrix type binder 60~90%.
Wherein, the suppository base is emulsion-type matrix.
Wherein, the emulsion-type matrix may be selected itself have hydrophily and the matrix of emulsifiability, such as the poly- hydrocarbon of stearic acid
Oxygen (40) ester etc..In order to further improve the effect of the slow release long-acting of suppository, the emulsion-type matrix is by water-soluble base, fat
Property matrix and surfactant composition.Wherein, the mass fraction of water-soluble base, fatty matrix and surfactant is as follows：
Water-soluble base 67~89.5%
Fatty matrix 10~30%
Surfactant 0.5~3%.
The water-soluble base is one in polyethylene glycols, poloxamer class, polyoxyl stearate and glycerin gelatine
Kind is two or more.The polyethylene glycols matrix (PEG) including PEG200, PEG400, PEG1500, PEG4000 and
One or more of PEG6000.The poloxamer class matrix is by poloxamer and the arbitrary proportion group of propylene glycol
Into including models such as poloxamers 108/124/127/188/237/338/407.
Wherein, the fatty matrix is one kind of semi-synthetic fatty acid glycerine lipid, natural acid ester and hydrogenated oil and fat
It is or two or more.The semi-synthetic fatty acid glycerine lipid includes glycerine fatty acid esters, such as glyceryl monostearate, glycerine list
Laurate, Compritol 888 ATO, cocounut oil ester and palmitate etc.；And sucrose-fatty esters, as sucrose monostearate,
Sucrose list palmitic acid acid esters etc..The natural acid ester includes cocoa butter, spicebush oil, oleum sapii, fennel fat and betel nut fat
Deng.
Wherein, nonionic surface active agent of the preferred HLB value of the surfactant in the range of 8~40, it is described
Nonionic surface active agent is polyoxyethylene sorbitan fatty acid ester class, polyoxyethylene aliphatic alcohol ether class, polyoxyethylene
One or more of aliphatic alcohol ester and polyoxyethylene polypropylene copolymer.The polyoxylene sorbitan fatty acid
Esters (Tweens), including Tween 80, polysorbate60, polysorbate65 etc.；The polyoxyethylene aliphatic alcohol ether class including Kaifeng pool 35, is put down
Flat plus O, polyoxyethylene nonylphenol ether etc.；The polyoxyethylene fatty acid ester class, including Myrj 52, Myrj 53, Myrj 45 etc.；Polyoxyethylene gathers
Propylene copolymer class, including PLURONICS F87, poloxamer 237, poloxamer188 etc..
In order to realize above-mentioned second purpose, technical solution provided by the invention is such：A kind of above-mentioned progesterone
The preparation method of long-acting suppository, includes the following steps：
Step 1：Suppository base heating water bath and stirring are made into its melting；
Step 2：Progesterone and binder are added under water-bath in the suppository base melted obtained by step 1,700~
Mixing under 5000r/min rotating speeds, obtains mixed liquor；
Step 3：Step 2 gained mixed liquor is cooled to sticky shape, in disposable injection bolt mould, 20~25 DEG C is cooled to and goes out
Mould is to get the long-acting suppository of progesterone.
The present invention has the following advantages compared with conventional method：
1. the long-acting suppository of progesterone provided by the invention, progesterone slowly can be released persistently, toxic side effect is reduced, is subtracted
Few administration number of times increases the medication compliance of patient.
2. adding in binder in the long-acting suppository of progesterone provided by the invention, absorb water in high aqueous vaginal environment molten
It is swollen, suppository is made to attach on vaginal mucosa, achievees the effect that increase residence time and hold-up, increases drug effect amount and treatment
Effect.Further, the present invention makes preferably by the use of the binder of strong adhesion and the combination of matrix type binder as the binder of suppository
Suppository in use, binder in high aqueous vaginal environment can rapid water absorption and swelling, and attach on vaginal mucosa, more
Further increase the effect of residence time and hold-up.Therefore, the long-acting suppository of progesterone provided by the invention and ordinary suppository
Compare, there is larger adhesion so that suppository can be stranded in medicine-feeding part for a long time, reduce the leakage of drug, increase drug
Curative effect.
3. progesterone is fat-soluble medicine, water-soluble base is used alone, then makes medicine since matrix is dissolved in body fluid rapidly
Object release is very fast, can not meet the purpose of sustained release for a long time；Individually using fatty matrix then since matrix melting slowly makes
Drug release is relatively slow and can not discharge completely.Therefore the present invention uses emulsion-type matrix as suppository base.Emulsion-type base contains
The water-soluble base of large scale and the fatty matrix of small scale have high-hydrophilic and low lipophilicity, such part progesterone
It is dissolved in fatty matrix, another part is then dispersed in water-soluble base, therefore the suppository is in the application, is dispersed in water solubility
Progesterone in matrix first discharges, and the progesterone that small part is dissolved in fatty matrix is then slowly released with the melting of suppository
It releases so that drug achievees the effect that centainly to be sustained.
On the one hand 4. surfactant is added in the suppository base of the present invention can reduce water-soluble base and fatty base
Surface tension between matter is uniformly mixed the two；On the other hand fat-soluble progesterone can be made more uniformly to be dispersed in
In suppository base, drugloading rate is made to increase than ordinary suppository.
5. the formulation and technology of the long-acting suppository of progesterone is simple, it can be achieved that industrialized production.
Description of the drawings
Fig. 1 is the cumulative release curve graph for making the long-acting bolt of progesterone and common progesterone bolt by oneself.
Specific embodiment
With reference to embodiment, technical scheme of the present invention is described in further detail.
In following embodiment, stick time detection method in vitro：Zhu Xiu cities《Progesterone bio-adhesive slow-release suppository it is external
Study on evaluation way》, Guangdong pharmaceutical university, 2017,33 (2), 148-152.
Drug release rate is measured using blue laws is turned for 24 hours, is situated between by release of the 0.5%SDS-4 buffer solutions 500mL of fresh degassing
Matter, temperature are 37.0 ± 0.5 DEG C, rotating speed 30r/min.Precision weighs long-acting suppository, is placed in basket, respectively at the 1st, 2,4,6,
8,12,5mL is sampled for 24 hours, immediately using 0.22 μm of membrane filtration, and equivalent equality of temperature medium is replenished in time, by following chromatographic condition
It measures：Chromatographic column：Dimonsil C18 columns (4.6mm × 250mm, 5 μm)；Mobile phase：Methanol -- water (80:20)；Flow velocity：1mL/
min；Detection wavelength：245nm；Sample size：10μL；Column temperature：30℃.
Embodiment 1
Progesterone 1.5%；Binder 5%；Suppository base 93.5%.
Binder is made of 10% Polycarbophil and 90% hydroxypropyl methylcellulose.Suppository base is polyoxyethylene stearate (40)
Ester.
Step 1：Suppository base heating water bath and stirring are made into its melting.
Step 2：Under water-bath, progesterone and binder are added in the suppository base melted obtained by step 1, in 700r/min
Mixing under rotating speed, obtains mixed liquor.
Step 3：Step 2 gained mixed liquor is cooled to sticky shape, in disposable injection bolt mould, is cooled to 25 DEG C of depannings,
Up to the long-acting suppository of progesterone.
As a result：The long-acting suppository of gained progesterone is smooth complete milky suppository, sticks the time in vitro for 82.54s.
The cumulative release percentage of the long-acting suppository of progesterone and common progesterone bolt for preparing gained refers to Fig. 1.As a result may be used
See the long-acting suppository of progesterone in 2h without burst release, drug release rate is 90.7% for 24 hours.
Embodiment 2
Progesterone 4%；Binder 3%, suppository base 93%.
Binder is Polycarbophil.Suppository base is mixed by 84.5% poloxamer188,0.5% polysorbate 60 and 15%
Close 38 type of fatty glyceride composition.
Step 1：Suppository base heating water bath and stirring are made into its melting.
Step 2：Progesterone and binder are added in the suppository base melted obtained by step 1 under water-bath, in 5000r/min
Mixing under rotating speed, obtains mixed liquor.
Step 3：Step 2 gained mixed liquor is cooled to sticky shape, in disposable injection bolt mould, is cooled to 20 DEG C of depannings,
Up to the long-acting suppository of progesterone.
As a result:The long-acting suppository of progesterone is smooth complete milky suppository, sticks the time in vitro for 83.33s, for 24 hours medicine
Object release rate is 91.1%.
Embodiment 3
Progesterone 6%；Binder 2%；Suppository base 92%.
Binder is is made of 20% carbomer 934 and 80% chitosan.Suppository base be by 79% Macrogol 4000,
1% polyoxyethylene sorbitan monoleate and 20% mixed fatty glycerides, 40 type composition.
Step 1：Suppository base heating water bath and stirring are made into its melting.
Step 2：Progesterone and binder are added in the suppository base melted obtained by step 1 under water-bath, in 800r/min
Mixing under rotating speed, obtains mixed liquor.
Step 3：Step 2 gained mixed liquor is cooled to sticky shape, in disposable injection bolt mould, is cooled to 22 DEG C of depannings,
Up to the long-acting suppository of progesterone.
As a result:The long-acting suppository of progesterone is smooth complete milky suppository, sticks the time in vitro for 110.62s, for 24 hours medicine
Object preparation is about 90.4%.
Embodiment 4
Progesterone 1%；Binder 5%；Suppository base 94%.
Binder is CARBOPOL 974P.Suppository base is by 89% glycerin gelatine, 1% peregal O-25 and 10% behenic acid
Glyceride forms.
Step 1：Suppository base heating water bath and stirring are made into its melting.
Step 2：Progesterone and binder are added in the suppository base melted obtained by step 1 under water-bath, in 2500r/min
Mixing under rotating speed, obtains mixed liquor.
Step 3：Step 2 gained mixed liquor is cooled to sticky shape, in disposable injection bolt mould, is cooled to 24 DEG C of depannings,
Up to the long-acting suppository of progesterone.
As a result：The long-acting suppository of progesterone is smooth complete white suppository, sticks the time in vitro for 103.30s, for 24 hours drug
Preparation is 90.8%.
Embodiment 5
Progesterone 6%；Binder 5%；Suppository base 89%.
Binder is made of 10% Polycarbophil and 90% guar gum.Suppository base is by 74.5% polyoxyethylene stearate (40)
Ester, 0.5% PLURONICS F87 and 25% cocoa butter.
Step 1：Suppository base heating water bath and stirring are made into its melting.
Step 2：Progesterone and binder are added in the suppository base melted obtained by step 1 under water-bath, in 3600r/min
Mixing under rotating speed, obtains mixed liquor.
Step 3：Step 2 gained mixed liquor is cooled to sticky shape, in disposable injection bolt mould, is cooled to 23 DEG C of depannings,
Up to the long-acting suppository of progesterone.
As a result：The long-acting suppository of progesterone is smooth complete white suppository, sticks the time in vitro for 78.36s, for 24 hours drug
Preparation is 91.5%.
The present invention can be summarized with others without prejudice to the concrete form of the spirit or essential characteristics of the present invention.The present invention's
The embodiment above can only all be considered the description of the invention rather than limitation, therefore every substantial technological according to the present invention
To any subtle modifications, equivalent variations and modifications that above example is made, belong in the range of technical solution of the present invention.
Claims (10)
1. a kind of long-acting suppository of progesterone, which is characterized in that be mainly made of following weight percent composition：
Progesterone 1~6%；
Binder 2~5%；
Suppository base 89~97%.
2. the long-acting suppository of progesterone according to claim 1, which is characterized in that the progesterone is using Li Jing≤75 μm
Corpus luteum micropowder.
3. the long-acting suppository of progesterone according to claim 1, which is characterized in that the binder is Polycarbophil, card wave
Nurse, hydroxypropyl methylcellulose, chitosan, sodium carboxymethylcellulose, polyvinylpyrrolidone, Sodium Hyaluronate, sodium alginate, Guar
The one or more of glue, xanthans and pectin.
4. the long-acting suppository of progesterone according to claim 3, which is characterized in that the binder sticks for strong adhesion
Agent and the combination of matrix type binder, the binder of the strong adhesion are one or both of Polycarbophil and carbomer, bone
Frame type binder is hydroxypropyl methylcellulose, chitosan, sodium carboxymethylcellulose, polyvinylpyrrolidone, Sodium Hyaluronate, seaweed
Sour sodium, guar gum, xanthans and pectin one or more.
5. the long-acting suppository of progesterone according to claim 4, which is characterized in that the binder and skeleton of the strong adhesion
The mass fraction of type binder is respectively：
The binder 10~40% of strong adhesion
Matrix type binder 60~90%.
6. the long-acting suppository of progesterone according to claim 1, which is characterized in that the suppository base is emulsion-type matrix.
7. the long-acting suppository of progesterone according to claim 6, which is characterized in that the emulsion-type matrix includes but not limited to
Polyoxyethylene stearate (40) ester.
8. the long-acting suppository of progesterone according to claim 6, which is characterized in that the emulsion-type matrix is by water-soluble base
Matter, fatty matrix and surfactant composition；Wherein, the matter of the water-soluble base, fatty matrix and surfactant
It is as follows to measure score：
Water-soluble base 67~89.5%
Fatty matrix 10~30%
Surfactant 0.5~3%.
9. the long-acting suppository of progesterone according to claim 8, which is characterized in that the water-soluble base is polyethylene glycol
One or more of class, poloxamer class, polyoxyl stearate and glycerin gelatine；The fatty matrix is hemizygous
Into the one or more of fatty acid glycerine lipid, natural acid ester and hydrogenated oil and fat.The surfactant exists for HLB value
Nonionic surface active agent in the range of 8~40, including but not limited to polyoxyethylene sorbitan fatty acid ester class, polyoxy second
One or more of alkene fatty alcohol ethers, polyoxyethylene fatty acid ester and polyoxyethylene polypropylene copolymer.
It is 10. a kind of such as the preparation method of the long-acting suppository of claim 1-9 any one of them progesterone, which is characterized in that including
Following steps：
Step 1：Suppository base heating water bath and stirring are made into its melting；
Step 2：Progesterone and binder are added under water-bath in the suppository base melted obtained by the step 1,700~
Mixing under 5000r/min rotating speeds, obtains mixed liquor；
Step 3：The step 2 gained mixed liquor is cooled to sticky shape, in disposable injection bolt mould, 20~25 DEG C is cooled to and goes out
Mould is to get the long-acting suppository of progesterone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810148692.2A CN108186553B (en) | 2018-02-13 | 2018-02-13 | Long-acting progesterone suppository and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810148692.2A CN108186553B (en) | 2018-02-13 | 2018-02-13 | Long-acting progesterone suppository and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108186553A true CN108186553A (en) | 2018-06-22 |
| CN108186553B CN108186553B (en) | 2020-10-02 |
Family
ID=62593373
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810148692.2A Active CN108186553B (en) | 2018-02-13 | 2018-02-13 | Long-acting progesterone suppository and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108186553B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114129507A (en) * | 2021-07-13 | 2022-03-04 | 浙江仙琚制药股份有限公司 | Progesterone gel composition and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07100191A (en) * | 1993-10-06 | 1995-04-18 | Daikyo Yakuhin Kogyo Kk | Sustained release suppository |
| WO2004096151A2 (en) * | 2003-04-29 | 2004-11-11 | The General Hospital Corporation | Methods and devices for the sustained release of multiple drugs |
| CN1889994A (en) * | 2003-12-10 | 2007-01-03 | 艾克若克斯Dds有限公司 | Method of treatment for undesired effect following transdermal or topical drug delivery |
| CN1891224A (en) * | 2005-07-07 | 2007-01-10 | 天津市中意畜牧科技发展有限公司 | Progestational hormone composition, and its slow-release suppository device and preparation of said device |
| CN101489529A (en) * | 2006-06-02 | 2009-07-22 | 梨树妇女保健公司 | Method of treating atrophic vaginitis |
| CN103239389A (en) * | 2013-06-03 | 2013-08-14 | 南京泽恒医药技术开发有限公司 | Preparation method of progestin sustained-release gel for treating threatened abortion |
-
2018
- 2018-02-13 CN CN201810148692.2A patent/CN108186553B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07100191A (en) * | 1993-10-06 | 1995-04-18 | Daikyo Yakuhin Kogyo Kk | Sustained release suppository |
| WO2004096151A2 (en) * | 2003-04-29 | 2004-11-11 | The General Hospital Corporation | Methods and devices for the sustained release of multiple drugs |
| CN1889994A (en) * | 2003-12-10 | 2007-01-03 | 艾克若克斯Dds有限公司 | Method of treatment for undesired effect following transdermal or topical drug delivery |
| CN1891224A (en) * | 2005-07-07 | 2007-01-10 | 天津市中意畜牧科技发展有限公司 | Progestational hormone composition, and its slow-release suppository device and preparation of said device |
| CN101489529A (en) * | 2006-06-02 | 2009-07-22 | 梨树妇女保健公司 | Method of treating atrophic vaginitis |
| CN103239389A (en) * | 2013-06-03 | 2013-08-14 | 南京泽恒医药技术开发有限公司 | Preparation method of progestin sustained-release gel for treating threatened abortion |
Non-Patent Citations (5)
| Title |
|---|
| 朱秀城等: "黄体酮生物黏附缓释栓的体外评价方法研究", 《广东医科大学学报》 * |
| 潘卫三主编: "《工业药剂学》", 30 June 2010 * |
| 王淑萍等: "乳剂型栓剂基质的处方筛选", 《武警医学院学报》 * |
| 马晓华等: "黏膜黏附材料在阴道给药中的应用", 《药学与临床研究》 * |
| 龙利红等: "黄体酮缓释栓的制备及药动学", 《中国医院药学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114129507A (en) * | 2021-07-13 | 2022-03-04 | 浙江仙琚制药股份有限公司 | Progesterone gel composition and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108186553B (en) | 2020-10-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11065197B2 (en) | Soluble estradiol capsule for vaginal insertion | |
| AU2019204653B2 (en) | Soluble Estradiol Capsule For Vaginal Insertion | |
| FI119498B (en) | Compositions for the treatment of hemorrhoids and method of use | |
| Lu et al. | Novel thermosensitive in situ gel based on poloxamer for uterus delivery | |
| CN102145003B (en) | Medicinal composition containing insoluble medicament | |
| CN109464400A (en) | Altrenogest solid pharmaceutical preparation and its preparation method and application | |
| CN101366715A (en) | Rapamycin composition and preparation thereof | |
| CN108186553A (en) | A kind of long-acting suppository of progesterone and preparation method thereof | |
| CN102525887A (en) | Cyclosporine-containing ophthalmic emulsion gel and preparation method thereof | |
| CN102309438B (en) | Midazolam medicament composition as well as preparation method and application thereof | |
| CN102000341B (en) | Polyethylene oxide and matrix type surfactant in suppository composition | |
| CN112336699A (en) | Progesterone vaginal slow-release soft capsule and its preparation method | |
| US20210100819A1 (en) | Pharmaceutical formulation for the treatment of inflammatory changes to the rectum | |
| JP2000509385A (en) | Compositions with biological activity | |
| CN105854022A (en) | Drug carrier capable of slowly releasing drug | |
| CN101332174A (en) | Dihydrotestosterone external preparation and pharmaceutical use thereof | |
| CN104257626A (en) | Secnidazole soft capsule and preparation method thereof | |
| CN104856942B (en) | Ciclopirox olamine vaginal dilation bolt and its preparation method | |
| CN106902074A (en) | A kind of rifaximin two-layer gel suppository for animals and preparation method thereof | |
| CN104688671A (en) | Compound suppository containing policresulen and preparation technology of compound suppository | |
| CN105796477A (en) | Butoconazole nitrate suppository and preparation method thereof | |
| CN1322853C (en) | Qinglianghou drop pill for treating common cold and throat disease and its preparation method | |
| CN118178321A (en) | Ke myc azole foam aerosol and its preparing method | |
| WO2012041966A1 (en) | Ovule for vaginal administration of arasertaconazole | |
| CN101224204A (en) | Butoconazole nitrate soft capsule for vagina and preparing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |