CN1235590C - Phenasteroid gel preparation - Google Patents
Phenasteroid gel preparation Download PDFInfo
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- CN1235590C CN1235590C CN 200410015700 CN200410015700A CN1235590C CN 1235590 C CN1235590 C CN 1235590C CN 200410015700 CN200410015700 CN 200410015700 CN 200410015700 A CN200410015700 A CN 200410015700A CN 1235590 C CN1235590 C CN 1235590C
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- finasteride
- ethosome
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Abstract
The present invention provides a phenasteroid gel preparation mainly comprising phenasteroamine, phosphatide, low molecular weight alcohol, glycerine, carbomer, an antioxidant, triethanolamine and solvent. A new transdermal medicine supply carrier of alcohol plastid is used by the phenasteroid gel preparation. The transdermal transportation of the phenasteroamine is improved to achieve the purposes of increasing medicament targeting tropism, extending medicament action time and keeping stable blood medicament concentration, and thus, the curative effect of the medicament is enhanced. The preparation has the advantages of simple preparation process, high encapsulation efficiency, good stable performance and small side effect. The phenasteroid gel preparation can be compatible with various medicament components. When the phenasteroid gel preparation is used for transdermal approach administration, the transdermal transportation of the medicament can be improved, and the curative effect of the medicament can be enhanced.
Description
Affiliated technical field
The invention belongs to pharmaceutical preparation, relate to the percutaneous dosing gel preparation of medicine, relate generally to Finasteride ethosome gel preparation, can improve the transport through skin of Finasteride, improve the hold-up of medicine in skin, the percutaneous that improves medicine absorbs, and improves curative effect.
Background technology
Since the percutaneous drug administration preparation-scopolamine of eighties of last century first listing at the beginning of the eighties came out, transdermal delivery system (TDDSs) just was a focus in the pharmaceutics research always.No matter what percutaneous absorbed generation is general action or local curative effect, medicine all needs percutaneous horny layer.Yet, because the good natural cover for defense effect of horny layer can not finely be brought into play the curative effect of many medicines.
A kind of novel vesicle drug administration carrier with lipid bilayer structure that ethosome (ethosomes) is made up of phospholipid, second alcohol and water, it compares the ethanol that contains higher concentration in the system with conventional liposome.Ethanol itself is a kind of good transdermal absorption accelerator, after it is wrapping in the phospholipid bilayer, can change the penetration performance of lipid film to skin, promotes the transport through skin of medicine better.In addition, ethosome has characteristics such as preparation technology is simple, envelop rate is high, stability is good, can improve the transport through skin of medicine, improves curative effect of medication.
Finasteride (finasteride) is a kind of synthetic steroid compound, has specificity, emulative 5 alpha reductase inhibitors, is 5 alpha reductase inhibitor medicines of first listing.Dihydrotestosterone is the one of the main reasons that causes benign prostatic hyperplasia (BPH) and male pattern alopecia, Finasteride can suppress the interior testosterone of human body and change into the stronger dihydrotestosterone (referring to Fig. 1) of androgen sample effect, is mainly used in the treatment of benign prostatic hyperplasia and male pattern alopecia.Finasteride can make that dihydrotestosterone concentration descends rapidly in the serum, makes it remarkable minimizing in administration in 24 hours, and it does not have affinity to androgen receptor, does not also have androgenic, androgen antagonist sample, estrogen-like, estrogen antagonist sample or gestagenic action.Hair follicle contains 5 alpha-reductases of higher concentration, and hair follicle tails off in male pattern baldness patient's alopecia district scalp, and dihydrotestosterone increases, and gives Finasteride and can make dihydrotestosterone lowering of concentration in these patient's scalps and the serum.Except the oral tablet of Finasteride, other dosage form is not gone on the market in the market.The Finasteride molecular weight is 372.55, and is fat-soluble, and a day administration metering is no more than 5mg, is a kind of comparatively ideal percutaneous dosing drug candidate.
Summary of the invention
The purpose of this invention is to provide a kind of Finasteride ethosome gel preparation, utilize this novel percutaneous dosing carrier of ethosome, improve the transport through skin of Finasteride, improve its therapeutic effect.
Finasteride ethosome gel preparation composition provided by the invention is mainly:
Finasteride 0.05～1%
Phosphatidase 10 .5～4%
Low-molecular-weight alcohol 10～45%
Glycerol 1～5%
Carbomer 0.25～1.5%
Antioxidant 0～3%
Triethanolamine 0.1～0.3%
Solvent 40.2～88.1%
The ethosome particle diameter of preparation of the present invention is at 50～800nm, preferred 50～400nm, and outward appearance is regular circular or ellipse.
Phospholipid is medicinal phospholipid in the preparation of the present invention, is mainly soybean phospholipid, two palmityl phospholipid, lecithin.
The used low-molecular-weight alcohol of preparation of the present invention is mainly ethanol, propylene glycol, preferred alcohol.
A kind of preparation method of preparation of the present invention is: prepare ethosome by injection method, and by ultrasonic, cross method such as microporous filter membrane and control its particle size.With carbomer water swelling, add a certain amount of glycerol, low-molecular-weight alcohol and antioxidant in addition, the reuse triethanolamine is regulated pH to neutral, adds the ethosome finished product of previous preparation then, obtains Finasteride ethosome gel preparation.
Characteristics of the present invention mainly are:
(1) Finasteride is prepared into ethosome by the transdermal penetration administration, reaching the targeting that increases medicine, prolong drug action time, keeps stable blood drug level, thereby improve the purpose of curative effect of medication.
(2) contain the low-molecular-weight alcohol of higher concentration in the ethosome of the present invention, it is a kind of good transdermal absorption accelerator, after it is wrapping in the phospholipid bilayer, can change the penetration performance of lipid film to skin, promotes the transport through skin of medicine.
(3) low-molecular-weight alcohol can improve the big dissolubility of fat-soluble medicine, can improve the drug loading and the envelop rate of ethosome.
(4) ethosome preparation technology of the present invention is simple, envelop rate is high, stability good, side effect is little, can with multiple ingredient compatibility, can improve the transport through skin of medicine when being used for the percutaneous administration, improve curative effect of medication.
(5) prepared ethosome can be mixed with percutaneous drug administration preparations such as liniment, gel, ointment and paster by regulating different prescription compositions and proportioning.
Description of drawings
Fig. 1 is the structure and the mechanism of action of Finasteride.
Fig. 2 is the transdermal penetration speed comparison diagram of each group sample.
Fig. 3 is 24 hours medicine accumulative total infiltration capacity comparison diagrams.
The specific embodiment
The invention will be further described below in conjunction with specific embodiment.
Several compositions of embodiment 1 preparation of the present invention
| Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | |
| Finasteride phosphatide low-molecular-weight alcohol carbomer glycerine antioxidant (vitamin E) triethanolamine water | 0.010 0.15 3.0 0.10 0.20 0 0.025 16.0 | 0.020 0.15 6.0 0.20 0.50 0.10 0.050 13.0 | 0.020 0.30 6.0 0.24 0.50 0.20 0.050 13.0 | 0.040 0.50 6.0 0.24 0.50 0.20 0.050 13.0 | 0.040 0.60 9.0 0.24 0.50 0.20 0.050 10.0 |
More than be 20g gel prescription proportioning, unit is gram.1,2,3 the low-molecular-weight alcohol of wherein writing out a prescription is an ethanol, and the low-molecular-weight alcohol of prescription 4,5 is a propylene glycol.
Several compositions in addition of embodiment 2 preparations of the present invention
| Prescription 6 | Prescription 7 | Prescription 8 | Prescription 9 | Prescription 10 | |
| Finasteride phosphatide low-molecular-weight alcohol carbomer glycerine antioxidant (vitamin E) triethanolamine water | 0.080 0.15 3.0 0.10 0.50 0.20 0.050 16.0 | 0.08 0.15 6.0 0.20 0.50 0.20 0.050 13.0 | 0.080 0.30 6.0 0.24 0.50 0.20 0.050 13.0 | 0.1 0.50 6.0 0.24 0.50 0.20 0.050 13.0 | 0.2 0.60 9.0 0.24 0.8 0.50 0.10 10.0 |
More than be 20g gel prescription proportioning, unit is gram.6,7,8 the low-molecular-weight alcohol of wherein writing out a prescription is an ethanol, and the low-molecular-weight alcohol of prescription 9,10 is a propylene glycol.
Embodiment 3 a kind of preparation methoies of the present invention
Get soybean phospholipid 300mg, Finasteride 25mg, ethanol 3.8ml, solvent 6.8ml, the ethanol that Finasteride and soybean phospholipid are dissolved in, thread injection buffer or water are to 10g under the room temperature airtight condition, obtain Finasteride ethosome suspension, by probe type ultrasonic (400～500w, 30～60 times), cross microporous filter membrane methods such as (0.1 microns or 0.22 micron) control ethosome particle diameter, obtain the finished product of Finasteride ethosome, by transmission electron microscope observation Finasteride ethosome sample form, the ethosome size is about 150nm, and outward appearance is regular circular or ellipse.
To be prepared into gel by the Finasteride ethosome that method for preparing obtains, its method is: in addition carbomer (0.5～1.5%) is used the suitable quantity of water swelling, add 1～5% glycerol, 15%～45% low-molecular-weight alcohol and 0～3% antioxidant, the reuse triethanolamine is regulated pH to neutral, add the Finasteride ethosome finished product of previous preparation then, obtain Finasteride ethosome gel preparation.
Embodiment 4
Water saturation solution, 30% alcoholic solution, liposome with Finasteride are contrast, the transdermal penetration characteristic of research ethosome gel.Remove the human body skin that removes subcutaneous tissue, after cleaning with normal saline, skin is fixed on the Franz diffusion cell of improvement, the PEG normal saline with 20% is an acceptable solution, adds an amount of sample of preparation before at supply chamber, and sealing.In the point in time sampling of setting, and the fresh acceptable solution of additional equivalent.After 24 hours, take off skin, water cleans and dries, and with cotton ball soaked in alcohol wiping skin surface for several times, the epidermal area of hot plate method separate skin and skin corium are smashed to pieces respectively, with 30% methanol extraction 24hr, measures medicament contg wherein.Result of study shows, no matter be the hold-up of medicine in skin or the stable state percutaneous rate of medicine, Finasteride ethosome system all will be better than matched group significantly, the result is referring to Fig. 2, Fig. 3, A. medicine saturated aqueous solution wherein, B. medicine 30% alcoholic solution, C. ethosome solution, D. ethosome gel, E. ethosome gel.
The partial reference document that the present invention relates to
[1]Gormley GJ.Finasteride：a clinical review[J].Biomed & Pharmacother，1995，49：319.
[2]Kirjavainen M，Urtti A，Valjakka-Koskela R，et al.Liposome-skininteractions and their effects on the skin permeation of drugs[J].Euro J Pharma Sci，1999，7：279.
[3]Bouwstra JA，Honeywell-Nguyen PL.Skin structure and mode of action ofvesicles[J].Adv Drug Del Rev，54 Suppl.2002，1：S41.
[4]Touitou E，Dayan N，Bergelson L，et al.Ethosomes-novel vesicularcarriers for enhanced delivery：characterization and skin penetration properties[J].JControlled Release，2000，65：403.
[5]Dayan N，Touitou E.Carriers for skin delivery of trihexyphenidyl HCl：ethosomes vs.liposomes[J].Biomaterials，2000，21：1879.
[6]Keith D，Kaufman.Androgens and alopecia[J].Molecular and CellularEndocrinology，2002，198：89.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Need not further to elaborate, believe and adopt the disclosed content in front, those skilled in the art can use to greatest extent, and these equivalent form of values fall within the application's appended claims institute restricted portion equally.In addition, the preferred specific embodiments of front should be understood that only to illustrate, but not limits the scope of the invention by any way.
Claims (2)
1. Finasteride ethosome gel preparation, ethosome is made up of medicine, phospholipid, ethanol, it is characterized in that: medicine is a Finasteride, and weight of formulation percentage ratio consists of:
Finasteride 0.05～1%
Soybean phospholipid 0.5～4%
Low-molecular-weight alcohol 10～45%
Glycerol 1～5%
Carbomer 0.25～1.5%
Vitamin E antioxidant 0～3%
Triethanolamine 0.1～0.3%
Water 40.2～88.1%
Wherein low-molecular-weight alcohol is selected ethanol or propylene glycol for use.
2. Finasteride ethosome gel preparation according to claim 1 is characterized in that: the ethosome particle diameter is at 50～800nm, and outward appearance is regular circular or ellipse.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410015700 CN1235590C (en) | 2004-01-06 | 2004-01-06 | Phenasteroid gel preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410015700 CN1235590C (en) | 2004-01-06 | 2004-01-06 | Phenasteroid gel preparation |
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| CN1555804A CN1555804A (en) | 2004-12-22 |
| CN1235590C true CN1235590C (en) | 2006-01-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410015700 Expired - Fee Related CN1235590C (en) | 2004-01-06 | 2004-01-06 | Phenasteroid gel preparation |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101574373B (en) * | 2008-05-09 | 2013-06-12 | 北京因科瑞斯医药科技有限公司 | Toad venom alcohol plastid and preparation method thereof |
| CN101948506A (en) * | 2010-08-13 | 2011-01-19 | 吉林省创新医药公共服务平台有限责任公司 | Finasteride conjugate and application thereof to preparation of medicament for treating prostate |
| CN102552147B (en) * | 2011-02-11 | 2013-06-05 | 舒泰神（北京）生物制药股份有限公司 | Bullatacin ethosome gel and preparation method thereof |
| CN105919938A (en) * | 2016-04-27 | 2016-09-07 | 浙江大学 | Cryptotanshinone ethosome, and preparation method and application thereof |
| CN106074365B (en) * | 2016-07-26 | 2019-05-03 | 西安艾尔菲生物科技有限公司 | A kind of capsaicine ethosome gel and preparation method thereof |
| CN106361703A (en) * | 2016-10-31 | 2017-02-01 | 长沙晶易医药科技有限公司 | Finasteride nano-liposome, gel and preparation method thereof |
| CN106943341B (en) * | 2017-05-10 | 2020-01-24 | 重庆理工大学 | External preparation for improving transdermal absorption of usnic acid and application of external preparation in promoting healing of skin wound |
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