CN110448525A - A kind of external application Finasteride lipid nanometer preparation and preparation method thereof prevented hair loss with growth-promoting hair - Google Patents
A kind of external application Finasteride lipid nanometer preparation and preparation method thereof prevented hair loss with growth-promoting hair Download PDFInfo
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Abstract
The present invention relates to a kind of external application Finasteride lipid nanometer preparations and preparation method thereof prevented hair loss with growth-promoting hair.Specifically, the present invention provides a kind of Finasteride lipid nano particle, and the lipid nano particle includes: (1) Finasteride；(2) pharmaceutically acceptable nanoparticle auxiliary material, comprising: (a) matrix material；(b) emulsifier；(c) assistant for emulsifying agent；(d) oily phase；(e) water phase；The partial size of the Finasteride lipid nanometer preparation is 1-1000nm.Finasteride lipid nano particle of the present invention can effective softening skin cuticula, effectively increase the efficiency that drug enters hair follicle cell, play sustained release effect, prolonged application safety is higher.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, more particularly to a kind of external application Finasteride rouge prevented hair loss with growth-promoting hair
Matter nanometer formulation and preparation method thereof.
Background technique
Male androgen type baldness is also known as male pattern alopecia or seborrheic baldness, is a kind of common male's hair disease
Disease.Research in recent years shows that male androgen type baldness is mainly horizontal related to inherent cause and internal protona.Protona
It is internal androgenic testosterone through the II type 5a- reduction resulting product of enzyme catalysis, the affinity with androgen receptor is about testis
5 times of ketone.Separately there is studies have shown that 5a- reductase to be largely present in hair follicle root sheath and blood, the II type 5a- of excessive level is also
It is horizontal that protoenzyme can dramatically increase protona in hair follicle and blood plasma.Protona can be with the androgen receptor knot on hair follicle inner cell
It closes, causes a series of trichomadesis reactions, so as to cause the generation of baldness.
Finasteride is a kind of 4- aza steroid (formula 1), it is testosterone metabolism as during protona
The specific inhibitor of desmoenzyme II type 5a- reductase, can block testosterone to protona convert, thus reduce serum and
Protona level in hair follicle tissue is to reach containment or reverse the generation of baldness.Has the Finasteride preparation of listing at present
It is oral preparation for hair growth, trade name is protected method and stopped, and recommended dose is daily 1mg.Clinical study results show have
There is related with medication adverse reaction, including sexual hypoesthesia, impotence etc. after taking orally Finasteride in >=1% male patient.Cause
This, develops a kind of part Finasteride preparation tool that can be acted locally on hair follicle tissue, be avoided taking orally caused side effect
It is significant.
In recent years, the research for being used to treat male androgen type baldness about external application Finasteride preparation obtains researcher's
Extensive concern.But since Finasteride water solubility is very poor, and stability is lower, and it is higher that external preparation prepares difficulty.Patent
CN100342855C discloses a kind of activating element for preventing baldness, wherein containing Finasteride and other hair tonic ingredients.It is wherein non-
That male amine be pulverize it is last after be scattered in aqueous medium, partial size is big, and local absorption effect is poor.Patent CN103596550A
A kind of composition for preventing hair loss with trichogenous local use is disclosed, wherein containing 5α-reductase and rice
Promise ground you.Its preparation contains 40% ethyl alcohol and 50% propylene glycol, and long-time service easily leads to the allergic reactions such as scalp pruritus or dandruff,
There are some potential safety problemss.Patent CN104768539A and CN104755075A individually disclose a kind of Finasteride polymer
Nanoparticle and a kind of Finasteride and minoxidil polymer nano-particle are used for hair growth.It is poly- that it uses slightly solubilities
Object material poly-epsilon-caprolactone is closed, preparation partial size is larger, about 200nm, into hair follicle cell low efficiency；And preparation process need to use third
The organic solvents such as ketone, ethyl acetate, preparation process is complicated, and there are environmental pollution hidden danger.
Therefore, this field needs to develop a kind of Finasteride novel formulation, improves the therapeutic effect of Finasteride, reduces patient
Pain, improve the quality of living.
Summary of the invention
The purpose of the present invention is to provide a kind of external application Finasteride lipid nanometer preparations prevented hair loss with growth-promoting hair.
The first aspect of the present invention, provides a kind of Finasteride lipid nano particle, and the lipid nano particle includes:
(1) Finasteride；
(2) pharmaceutically acceptable nanoparticle auxiliary material, comprising:
(a) matrix material；
(b) emulsifier；
(c) assistant for emulsifying agent；
(d) oily phase；With
(e) water phase；
The partial size of the Finasteride lipid nanometer preparation is 1-1000nm.
In another preferred example, the partial size of Finasteride lipid nanometer preparation is 2-200nm, more preferably 2-80nm.
In another preferred example, the content of the Finasteride is 0.0001-5 parts by weight, preferably 0.01-0.3 parts by weight；
And/or
The content of the matrix material is 0.1-20 parts by weight, preferably 0.5-5 weight；And/or
The content of the emulsifier is 0.01-50 parts by weight, preferably 0.5-20 parts by weight, more preferably 0.5-10 weight
Part, more preferably 0.5-5 parts by weight；And/or
The content of the assistant for emulsifying agent is 1-60 parts by weight, preferably 10-20 parts by weight；And/or
The content of the oil phase is 0.1-60 parts by weight, preferably 0.2-10, more preferably 2-10 parts by weight；And/or
The content of the water phase is 10-90 parts by weight, preferably 60-90 parts by weight.
In another preferred example, the matrix material is selected from the group: cholesterol, soybean lecithin, egg yolk lecithin, phosphatidyl
Choline, phosphatidic acid, phosphatidyl glycerol, phosphatidylinositols, phosphatidyl serine, synthetic phospholipid derivative, or combinations thereof.
In another preferred example, the emulsifier is selected from the group: Arabic gum, tragacanth, gelatin, fatty acid salt,
Higher aliphatic alcohol sulfuric ester, fatty glyceride, fatty acid sorbitan, polysorbate, poloxamer, is gathered higher fatty acid salt
Ethylene oxide aliphatic ester, polyoxyethylene aliphatic alcohol ether, polyoxyethylene alcohol, Emulsifier EL-60, sodium taurocholate, albumin, beeswax,
Or combinations thereof.
In another preferred example, the poloxamer is PLURONICS F87
In another preferred example, the higher fatty acid salt is enuatrol.
In another preferred example, the higher aliphatic alcohol sulfuric ester is lauryl sodium sulfate.
In another preferred example, the polysorbate is polyoxyethylene sorbitan monoleate.
In another preferred example, the assistant for emulsifying agent is selected from the group: ethyl alcohol, propylene glycol, butanediol, n-butanol, penta 2
The short chain alcohols such as alcohol, glycerol, polyethylene glycol, two glycosides alcohol list ether, or combinations thereof.
In another preferred example, the oil is mutually selected from the group: in vegetable oil, unsaturation/long chain triglycerides, fatty acid
Ester, or combinations thereof.
In another preferred example, the vegetable oil is selected from the group: corn oil, peanut oil, olive oil, soybean oil, sesame
Oil, oil with hydrogenated soybean, peppermint oil, caryophyllus oil, or combinations thereof.
In another preferred example, in the unsaturation/long chain triglycerides are selected from the group: chain fatty acid triglycerides,
MCT Oil, or combinations thereof.
In another preferred example, the aliphatic ester is selected from the group: ethyl oleate, butyl oleate, myristic acid isopropyl
Rouge, Miglyol 812, triglycerin caprylate, triglycerin certain herbaceous plants with big flowers acid esters, or combinations thereof.
In another preferred example, the pharmaceutically acceptable nanoparticle auxiliary material further includes gel component.
In another preferred example, the gel component is selected from the group: glycerol, poloxamer, carboxymethyl cellulose, collagen egg
The sub- glue of white, hyaluronic acid, xanthan gum, gelatin, Arabic gum, sand sagebrush (Artemisia filifolia), or combinations thereof.
In another preferred example, the gel component is gel skin care ingredient.
In another preferred example, the content of the gel component is 0.1-60 parts by weight, and preferred 0.1-10 parts by weight are more excellent
Select 0.2-10 parts by weight, more preferably 0.2-8 parts by weight.
In another preferred example, the pharmaceutically acceptable nanoparticle auxiliary material further includes preservative.
In another preferred example, the preservative is selected from the group: parabens, benzoic acid, benzoate,
Sorbic acid, sorbate, benzalkonium bromide, chlorhexidine acetate, o-phenyl phenol, eucalyptus oil, peppermint oil, cassia oil, or combinations thereof.
In another preferred example, the content of the preservative is 0-2 parts by weight, preferably 0.01-0.2 parts by weight.
The second aspect of the present invention provides a kind of Finasteride preparation, and the preparation includes such as first aspect present invention institute
The Finasteride lipid nano particle and pharmaceutically acceptable carrier stated.
In another preferred example, the preparation is solution, cream, emulsion agent, gelling agent, suspension or patch.
In another preferred example, the Finasteride preparation is Finasteride lipid nano particle gelling agent, and described is non-
That male amine lipid nano particle gelling agent includes Finasteride lipid nano particle as described in the first aspect of the invention, and pharmaceutically may be used
The gel carrier of receiving；
Wherein, the gel carrier includes one or more gel-type vehicles selected from the group below: carbomer, and glycerol moors Lip river
Sha Mu, carboxymethyl cellulose, collagen, hyaluronic acid, xanthan gum, gelatin, the sub- glue of Arabic gum, sand sagebrush (Artemisia filifolia), or combinations thereof.
In another preferred example, the gel carrier further includes pH adjusting agent selected from the group below: triethylamine, three ethyl alcohol
Amine, ammonium hydroxide, sodium hydroxide, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, hydrochloric acid, phosphoric acid, citric acid, acetic acid, or combinations thereof.
In another preferred example, the gel carrier further includes antioxidant selected from the group below: sodium sulfite, sulfurous acid
Hydrogen sodium, sodium pyrosulfite, vitamin C, vitamin E, or combinations thereof.
In another preferred example, the gel carrier further includes moisturizer selected from the group below: propylene glycol, glycerol, fourth two
Alcohol, polyethylene glycol, pentanediol, hydroxyethyl cellulose.
In another preferred example, the gel carrier further includes water.
In another preferred example, the content of the gel carrier be 0.1%-90%, preferably 10-90%, more preferably
For 10-70%, more preferably 10-40%, more preferably 10-30%, wherein the content is in terms of the gross mass of gelling agent.
In another preferred example, the pharmaceutically acceptable gel carrier includes: the gel base of 0.5-3 parts by weight
Matter, the moisturizer of 5-20 parts by weight, the pH adjusting agent of 1-4 parts by weight, 0.1-2 parts by weight antioxidant and 5-25 parts by weight
Water.
In another preferred example, the gel-type vehicle is selected from the group: carbomer, glycerol, poloxamer, carboxymethyl cellulose
Element, collagen, hyaluronic acid, xanthan gum, gelatin, the sub- glue of Arabic gum, sand sagebrush (Artemisia filifolia), or combinations thereof.
In another preferred example, the pharmaceutically acceptable gel carrier include: 0.5-3 parts by weight carbomer,
The moisturizer of 5-20 parts by weight, the pH adjusting agent of 1-4 parts by weight, 0.1-2 parts by weight antioxidant and 5-25 parts by weight water.
In another preferred example, the Finasteride preparation is Finasteride lipid nano particle cream, the cream
Paste includes Finasteride lipid nano particle and pharmaceutically acceptable emulsifiable paste carrier as described in the first aspect of the invention；
Wherein, the pharmaceutically acceptable emulsifiable paste carrier includes one or more emulsifiable paste matrixes selected from the group below: high
Grade fatty acid, paraffin, beeswax, higher aliphatic, vaseline, vegetable oil, soaps, lauryl sodium sulfate, polyalcohol fat
Acid esters, poly yamanashi esters, monoglyceride, polyoxyethylene ether, or combinations thereof.
In another preferred example, the higher fatty acids is stearic acid.
In another preferred example, the content of the pharmaceutically acceptable emulsifiable paste carrier is 0.1%-90%, preferably
10-90%, more preferably 10-70%, more preferably 10-40%, more preferably 10-30%, wherein the content is with emulsifiable paste
The gross mass meter of agent.
In another preferred example, the pharmaceutically acceptable emulsifiable paste carrier includes 1-20 higher aliphatic, 0.5-8 weight
Measure the aliphatic ester of part polyalcohol, the higher fatty acids of 0.2-5 parts by weight, the paraffin of 0.5-15 parts by weight and 0.3-8 parts by weight
Vaseline.
The third aspect of the present invention provides a kind of method for preparing lipid nano particle as described in the first aspect of the invention, institute
The method stated comprising steps of
By Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oil mutually and water phase mix, after obtain Finasteride lipid
Nanoparticle.
In another preferred example, the mixed method is paddling process, ultrasonic method, homogeneous method or microjet method.
In another preferred example, the method includes the steps:
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oily phase, water phase and additive mixing, in 0-90 DEG C of condition
Under, with the mixing speed of 20-20000rpm, 1-60min is stirred, additive is added, is stirred, obtains Finasteride lipid and receive
The grain of rice.
In another preferred example, the method includes the steps:
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oily phase, water phase and additive mixing, in 0-90 DEG C of condition
Under, with the mixing speed of 20-15000rpm, 1-10min is stirred, ultrasound 1-60min, adds under the conditions of ultrasonic power 100-800W
Enter additive, be stirred, obtains Finasteride lipid nano particle.
In another preferred example, the method includes the steps:
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oily phase, water phase and additive mixing, in 0-90 DEG C of condition
Under, with the mixing speed of 20-15000rpm, 1-10min is stirred, homogeneous under the conditions of pressure 5-12Mpa recycles 1-10 times, adds
Enter gel component, be stirred, obtains Finasteride lipid nano particle.
In another preferred example, the method includes the steps:
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oily phase, water phase and/or preservative mixing, in 0-90 DEG C of item
Under part, with the mixing speed of 20-15000rpm, 1-10min is stirred, using microjet under the conditions of pressure 1000-20000psi,
Circulation 1-4 times is added gel component, is stirred, obtains Finasteride lipid nano particle.
The fourth aspect of the present invention provides a kind of lipid nano particle as described in the first aspect of the invention or such as the present invention the
The purposes of the two aspect Finasteride preparations is used to prepare prevention and/or hair growth or promotees hair tonic medicament.
The fifth aspect of the present invention provide it is a kind of for prevent and/or hair growth or growth-promoting hair method, the side
Method is comprising steps of give required object lipid nano particle as described in the first aspect of the invention or as described in respect of the second aspect of the invention
Finasteride preparation.
It should be understood that above-mentioned each technical characteristic of the invention and having in below (eg embodiment) within the scope of the present invention
It can be combined with each other between each technical characteristic of body description, to form a new or preferred technical solution.As space is limited, In
This no longer tires out one by one states.
Detailed description of the invention
Fig. 1 is the grain size distribution of Finasteride lipid nano particle prepared by the embodiment of the present invention 2.
Fig. 2 is the transmission electron microscope picture of Finasteride lipid nano particle prepared by the embodiment of the present invention 2.
Fig. 3 is the isolated mouse skin cumulative penetration curve figure (37 DEG C, m ± sd, n=3) of the embodiment of the present invention 43: right
According to group: 0.25% Finasteride regular solution agent (15% ethyl alcohol and 15% propylene glycol solution)；A group: Finasteride lipid nanometer
Grain gelling agent (is prepared) referring to 40 method of the present embodiment；B group: Finasteride lipid nano particle cream is (referring to the present embodiment 41
Method preparation)；C group: the Finasteride lipid nano particle (being prepared referring to 2 method of the present embodiment) containing gel component；D group: it is free of
The Finasteride lipid nano particle preparation of gel component (D group is prepared referring to 42 the method for embodiment).
Fig. 4 is medicine retention spirogram (37 DEG C, m ± sd, n=3) for 24 hours in the isolated mouse skin of the embodiment of the present invention 43:
Control group: 0.25% Finasteride regular solution agent (15% ethyl alcohol and 15% propylene glycol solution)；A group: Finasteride lipid is received
Grain of rice gelling agent (is prepared) referring to 40 method of the present embodiment；B group: Finasteride lipid nano particle cream is (referring to the present embodiment
41 methods preparation)；C group: the Finasteride lipid nano particle (being prepared referring to 2 method of the present embodiment) containing gel component；D group: no
Finasteride lipid nano particle preparation containing gel component (D group is prepared referring to 42 the method for embodiment).
Fig. 5 is in the embodiment of the present invention 44 respectively for percutaneous administration of (0.15mg/, one day, Finasteride lipid nanometer preparation
Twice) afterwards mouse hair growth result figure (m ± sd, n=10): A: for physiological saline；B group: 0.25% Finasteride is commonly molten
Liquor (15% ethyl alcohol and 15% propylene glycol solution；C group: Finasteride lipid nano particle gelling agent is (referring to 40 method of the present embodiment
Preparation)；D group: Finasteride lipid nano particle cream (is prepared) referring to 41 method of the present embodiment；E group: containing the non-of gel component
That male amine lipid nano particle (being prepared referring to 2 method of the present embodiment)；F group: the Finasteride lipid nano particle without gel component
Group (prepared by the method referring to the present embodiment 42).
Specific embodiment
The present inventor unexpectedly develops a kind of Finasteride lipid nano particle, contains by extensive and in-depth study
The Finasteride lipid nano particle for having gel component is still solution shape, is smeared convenient for preparation and packing, and being applied to after skin can shape
At gel, can effective softening skin cuticula, effectively increase the efficiency that drug enters hair follicle cell, play sustained release and make
With prolonged application safety is higher.Based on the above discovery, inventor completes the present invention.
Term
Unless otherwise defined, otherwise whole technologies used herein and scientific term all have such as fields of the present invention
The normally understood identical meanings of those of ordinary skill.
As used herein, term " therapeutically effective amount ", which refers to, generates function or active and can be by people to people and/or animal
And/or the amount that animal is received.It will be apparent to an ordinarily skilled person in the art that " therapeutically effective amount " can be with administration
Approach, the auxiliary material of drug used, the severity of disease and with difference situations such as other drugs drug combination and not
Together.
As used herein, term " includes " not only includes closed definition, also includes semiclosed, open definition.Change speech
It, the term include " by ... constitute ", " substantially by ... constitute ".
Finasteride lipid nano particle
The present invention provides a kind of Finasteride lipid nano particle, and the lipid nano particle includes:
(1) Finasteride；
(2) pharmaceutically acceptable nanoparticle auxiliary material, the auxiliary material include:
(a) matrix material；
(b) emulsifier；
(c) assistant for emulsifying agent；
(d) oily phase；With
(e) water phase；
The partial size of the Finasteride lipid nanometer preparation is 1-1000nm.
Finasteride lipid nano particle of the present invention is one of emulsification system, and wherein partial size not only influences lipid
The physical and chemical performance of nanoparticle, while also the internal drug effect of lipid nano particle is had a huge impact, different-grain diameter range
Different influences is generated to lipid nano particle performance.The partial size of Finasteride lipid nano particle of the present invention is preferably 2-
200nm, most preferably 2-80nm.The percutaneous permeability of Finasteride lipid nano particle in this particle size range is stronger.
The present inventor is screened and is optimized to the dosage of the Finasteride lipid nano particle component by experiment,
Improve the therapeutic effect of Finasteride lipid nano particle.In a preferred embodiment, the content of the Finasteride is 0.0001-5
Parts by weight, preferably 0.01-0.3 parts by weight；And/or
The content of the matrix material is 0.1-20 parts by weight, preferably 0.5-5 weight；And/or
The content of the emulsifier is 0.01-50 parts by weight, preferably 0.5-20 parts by weight, more preferably 0.5-10 weight
Part, more preferably 0.5-5 parts by weight；And/or
The content of the assistant for emulsifying agent is 1-60 parts by weight, preferably 10-20 parts by weight；And/or
The content of the oil phase is 0.1-60 parts by weight, preferably 0.2-10, more preferably 2-10 parts by weight；And/or
The content of the water phase is 10-90 parts by weight, preferably 60-90 parts by weight.
Matrix material
In Finasteride lipid nano particle of the present invention, especially he does not limit the matrix material, only
Meet the purpose of the present invention.In a preferred embodiment, the matrix material includes but is not limited to: cholesterol, soybean
Phosphatide, egg yolk lecithin, phosphatidyl choline, phosphatidic acid, phosphatidyl glycerol, phosphatidylinositols, phosphatidyl serine, synthetic phospholipid
Derivative, or combinations thereof.
Emulsifier
Finasteride lipid nano particle of the present invention is one of emulsification system, wherein the emulsifier rises
To emulsification, in a preferred embodiment, the emulsifier includes but is not limited to: Arabic gum, tragacanth, gelatin,
Fatty acid salt, higher fatty acid salt, higher aliphatic alcohol sulfuric ester, fatty glyceride, fatty acid sorbitan, polysorbate, pool
Luo Shamu, polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether, sodium taurocholate, albumin, beeswax, or combinations thereof.
In another preferred example, the poloxamer is PLURONICS F87
In another preferred example, the higher fatty acid salt is enuatrol.
In another preferred example, the higher aliphatic alcohol sulfuric ester is lauryl sodium sulfate.
In another preferred example, the polysorbate is polyoxyethylene sorbitan monoleate.
Assistant for emulsifying agent
In Finasteride lipid nano particle of the present invention, the assistant for emulsifying agent can play the effects of helping emulsification, stablizing.
In a preference of the invention, the assistant for emulsifying agent includes but is not limited to: ethyl alcohol, propylene glycol, butanediol, positive fourth
The short chain alcohols such as alcohol, pentanediol, glycerol, polyethylene glycol, two glycosides alcohol list ether, or combinations thereof.
Oily phase
It is not particularly limited in the selection of Finasteride lipid nano particle of the present invention, the oil phase, as long as
Meet the purpose of the present invention.A in a preferred embodiment, the oil mutually includes but is not limited to: vegetable oil, unsaturation
In/long chain triglycerides, aliphatic ester, or combinations thereof.
Representative, the vegetable oil includes but is not limited to: corn oil, peanut oil, olive oil, soybean oil, sesame
Oil, oil with hydrogenated soybean, peppermint oil, caryophyllus oil, or combinations thereof.
It is representative, in the unsaturation/long chain triglycerides (including but not limited to): chain fatty acid triglycerides,
MCT Oil, or combinations thereof.
Representative, described aliphatic ester (including but not limited to): ethyl oleate, butyl oleate, myristic acid isopropyl
Rouge, Miglyol 812, triglycerin caprylate, triglycerin certain herbaceous plants with big flowers acid esters, or combinations thereof.
Water phase
In the present invention, water phase refers to water, and water is as solvent.Water for use in the present invention is not particularly limited, can be with
Purified water, distilled water, deionized water, water for injection, or combinations thereof.
Gel component
Gel component can also be contained in Finasteride lipid nano particle of the present invention.Containing gel component it is non-that
Male amine lipid nano particle is still solution shape, can form gel after being applied to skin, being capable of effective softening skin cuticula, effectively increasing
Dosing object enters the efficiency of hair follicle cell, plays sustained release effect, and prolonged application safety is higher.
In a preferred embodiment, the gel component (including but not limited to): glycerol, poloxamer, carboxymethyl cellulose
The sub- glue of element, collagen, hyaluronic acid, xanthan gum, gelatin, Arabic gum, sand sagebrush (Artemisia filifolia), or combinations thereof.In another preferred example, institute
The gel component stated is gel skin care ingredient.
In another preferred example, the Finasteride lipid nano particle also contains gel component, the gel component
Content is 0.1-60 parts by weight, preferably 0.1-10 parts by weight, more preferable 0.2-10 parts by weight, more preferably 0.2-8 parts by weight.
Nanoparticle-gel binary system is formed after Finasteride lipid nano particle medication containing gel component, on the one hand
Using the nanometer size effect of nano particle, effectively increases drug and enter hair follicle cell efficiency；On the other hand gel pair is utilized
The adhesion of skin, makes nanoparticle be firmly attached to skin surface, can effective softening skin cuticula, promote the suction of drug
It receives, comprehensive part of improving prevents hair loss curative effect；Gel component (such as hyaluronic acid, collagen or gelatin isogel type ingredient) is also
Preserving moisture and protecting skin can be played, improve the safety of this product prolonged application.
Preservative
In Finasteride lipid nano particle of the present invention, the selection of the preservative is not particularly limited, only
Meet the purpose of the present invention.Representative, the preservative includes but is not limited to: parabens,
Benzoic acid, benzoate, sorbic acid, sorbate, benzalkonium bromide, chlorhexidine acetate, o-phenyl phenol, eucalyptus oil, peppermint oil,
Cassia oil, or combinations thereof.
In another preferred example, the content of the preservative is 0-2 parts by weight, preferably 0.01-0.2 parts by weight.
Preparation
The present invention also provides a kind of Finasteride preparation, the preparation includes Finasteride lipid of the present invention
Nanoparticle and pharmaceutically acceptable carrier.
Finasteride preparation can be solution, cream, emulsion agent, gelling agent, suspension or patch.Preferably, institute
The Finasteride preparation stated is gelling agent or cream.
In a preferred embodiment, the Finasteride preparation is Finasteride lipid nano particle gelling agent, and described is non-
That male amine lipid nano particle gelling agent includes Finasteride lipid nano particle of the present invention and pharmaceutically acceptable gel
Carrier；
Wherein, the gel carrier includes one or more gel-type vehicles selected from the group below: carbomer, and glycerol moors Lip river
Sha Mu, carboxymethyl cellulose, collagen, hyaluronic acid, xanthan gum, gelatin, the sub- glue of Arabic gum, sand sagebrush (Artemisia filifolia), or combinations thereof.
Term " pharmaceutically acceptable carrier " refers to: one or more biocompatible solids, semisolid, liquid etc. are filled out
Material, they are suitable for human body or animal uses and it is necessary to have enough purity and sufficiently low toxicity, and have compatibility.
" compatibility " refer to each component in preparation and active pharmaceutical ingredient and they between can mutually admix, without reduce
Drug effect.
In another preferred example, the gel carrier further includes (but being not limited to) pH adjusting agent selected from the group below: three second
Amine, triethanolamine, ammonium hydroxide, sodium hydroxide, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, hydrochloric acid, phosphoric acid, citric acid, acetic acid,
Or combinations thereof.
In another preferred example, the gel carrier further includes (but being not limited to) antioxidant selected from the group below: sulfurous
Sour sodium, sodium hydrogensulfite, sodium pyrosulfite, vitamin C, vitamin E, or combinations thereof.
In another preferred example, the gel carrier further includes (but being not limited to) moisturizer selected from the group below: propylene glycol,
Glycerol, butanediol, polyethylene glycol, pentanediol, hydroxyethyl cellulose.
In another preferred example, the gel carrier further includes water.
In another preferred example, the content of the gel carrier be 0.1%-90%, preferably 10-90%, more preferably
For 10-70%, more preferably 10-40%, more preferably 10-30%, wherein the content is in terms of the gross mass of gelling agent.
In another preferred example, the pharmaceutically acceptable gel carrier includes: the gel base of 0.5-3 parts by weight
Matter, the moisturizer of 5-20 parts by weight, the pH adjusting agent of 1-4 parts by weight, 0.1-2 parts by weight antioxidant and 5-25 parts by weight
Water.
In another preferred example, the pharmaceutically acceptable gel carrier include: 0.5-3 parts by weight carbomer,
The moisturizer of 5-20 parts by weight, the pH adjusting agent of 1-4 parts by weight, 0.1-2 parts by weight antioxidant and 5-25 parts by weight water.
In another preferred example, the Finasteride preparation is Finasteride lipid nano particle cream, the cream
Paste includes Finasteride lipid nano particle of the present invention and pharmaceutically acceptable emulsifiable paste carrier；
Wherein, the pharmaceutically acceptable emulsifiable paste carrier includes one or more emulsifiable paste matrixes selected from the group below: high
Grade fatty acid, paraffin, beeswax, higher aliphatic, vaseline, vegetable oil, soaps, lauryl sodium sulfate, polyalcohol fat
Acid esters, poly yamanashi esters, monoglyceride, polyoxyethylene ether, or combinations thereof.
In another preferred example, the higher fatty acids is stearic acid.
In another preference, the higher aliphatic is octadecyl alcolol.
In another preference, the aliphatic ester of the polyalcohol is glycerin monostearate.
In another preferred example, the content of the pharmaceutically acceptable emulsifiable paste carrier is 0.1%-90%, preferably
10-90%, more preferably 10-70%, more preferably 10-40%, more preferably 10-30%, wherein the content is with emulsifiable paste
The gross mass meter of agent.
In another preferred example, the pharmaceutically acceptable emulsifiable paste carrier includes 1-20 higher aliphatic, 0.5-10
The aliphatic ester of weight polyol, the higher fatty acids of 0.2-6 parts by weight, the paraffin of 0.5-15 parts by weight and 0.3-8 weight
The vaseline of part.
Lipid nano particle preparation method
The present invention also provides a kind of preparation method of Finasteride lipid nano particle, the method comprising steps of
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oil are mutually mixed with water phase, Finasteride lipid is obtained and receives
The grain of rice.
In another preferred example, the homogenized method is paddling process.It is representative, the lipid nano particle preparation method
Comprising steps of
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oily phase, water phase and additive mixing, in 0-90 DEG C of condition
Under, with the mixing speed of 20-20000rpm, 1-60min is stirred, additive is added, is stirred, obtains Finasteride lipid and receive
The grain of rice.
In another preferred example, the homogenized method is ultrasonic method.It is representative, the lipid nano particle preparation method
Comprising steps of
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oily phase, water phase and additive mixing, in 0-90 DEG C of condition
Under, with the mixing speed of 20-15000rpm, 1-10min is stirred, ultrasound 1-60min, adds under the conditions of ultrasonic power 100-800W
Enter additive, be stirred, obtains Finasteride lipid nano particle.
In another preferred example, the homogenized method is homogeneous method.It is representative, the lipid nano particle preparation method
Comprising steps of
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oily phase, water phase and additive mixing, in 0-90 DEG C of condition
Under, with the mixing speed of 20-15000rpm, 1-10min is stirred, homogeneous under the conditions of pressure 5-12Mpa recycles 1-10 times, adds
Enter additive, be stirred, obtains Finasteride lipid nano particle.
In another preferred example, the homogenized method is microjet method.It is representative, the lipid nano particle preparation side
Method comprising steps of
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oily phase, water phase and additive mixing, in 0-90 DEG C of condition
Under, with the mixing speed of 20-15000rpm, stirs 1-10min and followed using microjet under the conditions of pressure 1000-20000psi
Ring 1-4 times is added gel component, is stirred, obtains Finasteride lipid nano particle.
Purposes
The present invention also provides a kind of Finasteride lipid nano particle of the present invention or Finasteride systems of the present invention
The purposes of agent is used to prepare prevention and/or hair growth and promotees hair tonic medicament.
The method of prevention and/or hair growth
The present invention also provides a kind of prevention and/or the methods of hair growth, and the method includes step, right needed for giving
As lipid nano particle of the present invention or with Finasteride preparation of the present invention.
Main advantages of the present invention include:
1, the present invention contains Finasteride in lipid nano particle core, compared with common Finasteride solution, to de-
Hair treatment has superior therapeutic effect.
2, in lipid nano particle, gel component is added.Nanoparticle-gel binary system can be formed after the medication of part,
On the one hand the nanometer size effect (< 100nm) that lipidic nanoparticles can be utilized, effectively increases drug and enters hair follicle cell efficiency；
On the other hand so that nanoparticle is firmly attached to skin surface the adhesion of skin using gel, promote to absorb, it is comprehensive to improve
Part prevents hair loss curative effect.
3, gel component used herein is the Native Gels ingredients such as hyaluronic acid, collagen or gelatin, is had more
Strong water-holding capacity, after smearing, can effective softening skin cuticula, effectively increase the efficiency that drug enters hair follicle cell.Outside it,
The gel component is similar to human body cell matrix composition, and prolonged application is highly-safe.
4, the present invention is similar to cell membrane composition using phosphatide or cholesterol lipid components as carrier, and biological safety is high.
Structure similar with cell membrane can also be utilized simultaneously, drug is promoted to enter hair follicle cell, play therapeutic effect.
5, Finasteride lipid nano particle system of the present invention be not necessarily to be centrifuged during the preparation process, micro porous filtration, i.e.,
Partial size can be prepared in the Finasteride lipid nanometer preparation of Nano grade, preparation process is simple, easy to industrialized production.
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip
Part, or according to the normal condition proposed by manufacturer.Unless otherwise stated, otherwise percentage and number are calculated by weight.
Embodiment 1- embodiment 39 is the preparation of Finasteride nanoparticle
Experimental studies have found that contain gel component in Finasteride lipid nano particle prepared by embodiment 1- embodiment 39,
Finasteride lipid nano particle is still solution shape, is smeared convenient for preparation and packing, and can form gel after being applied to skin, is played
Sustained release effect.
Embodiment 1
Paddling process prepares Finasteride lipid nano particle
By 0.15g Finasteride, 2g soybean lecithin, 5g butyl oleate, 1.2g PLURONICS F87,12g polyethylene glycol 400,
0.06g peppermint oil and the mixing of 79.59g water with the mixing speed of 1000rpm, stir 5min, are added 0.5% under the conditions of 10 DEG C
Collagen is stirred, and obtains Finasteride lipid nanometer preparation, and particle size range is placed at room temperature for 12 months in 100nm-180nm
Particle size range 120nm-200nm afterwards.
Embodiment 2
High pressure homogenization method prepares Finasteride lipid nano particle
By 0.15g Finasteride, 2g soybean lecithin, 5g butyl oleate, 1.2g PLURONICS F87,12g polyethylene glycol 400,
0.06g peppermint oil and the mixing of 79.59g water, with the mixing speed of 1000rpm, stir 5min, using high pressure under the conditions of 10 DEG C
Homogenizer recycles 5 times under the conditions of pressure 7MPa, and 0.5% collagen is added, is stirred, obtains Finasteride lipid nanometer
Preparation, particle size range is in 5nm-30nm, particle size range 5nm-30nm after being placed at room temperature for 12 months.
Lipid nano particle properties evaluations
Finasteride lipid nano particle is prepared according to 2 method of the present embodiment, is measured using METTLER TOLEDO pH meter
PH, pH are 5.42 ± 0.21；Its particle diameter distribution (Fig. 1) is measured using U.S.'s PSS company P380 type particle size analyzer, and using saturating
Its form (Fig. 2) of radio sem observation.
From figure 1 it appears that Finasteride lipid nanometer partial size prepared by embodiment 2 is 5nm-30nm.And distribution is good
It is good.From figure 2 it can be seen that liposome nano granule is spherical in shape, form is good.
Embodiment 3
Ultrasonic method prepares Finasteride lipid nano particle
By 0.15g Finasteride, 2g soybean lecithin, 5g butyl oleate, 1.2g PLURONICS F87,12g polyethylene glycol 400,
0.06g peppermint oil and the mixing of 79.59g water, with the mixing speed of 1000rpm, stir 5min, in ultrasonic function under the conditions of 10 DEG C
Ultrasound 15min under the conditions of rate 150W is added 0.5% collagen, is stirred, obtains Finasteride lipid nanometer preparation, partial size
Range is in 120nm-150nm, particle size range 100nm-160nm after being placed at room temperature for 12 months.
Embodiment 4
Microjet method prepares Finasteride lipid nano particle
By 0.15g Finasteride, 2g soybean lecithin, 5g butyl oleate, 1.2g PLURONICS F87,12g polyethylene glycol 400,
0.06g peppermint oil and the mixing of 79.59g water, with the mixing speed of 1000rpm, stir 5min, use microjet under the conditions of 10 DEG C
It under the conditions of pressure 1800psi, recycles 2 times, 0.5% collagen is added, is stirred, obtains Finasteride lipid nanometer system
Agent, particle size range is in 40nm-70nm, particle size range 30nm-70nm after being placed at room temperature for 12 months.
Method in following embodiment 5- embodiments 39 is unless otherwise specified under the conditions of 10 DEG C, with 1000rpm
Mixing speed, stir 5min, use high pressure homogenizer under the conditions of pressure is for 7Mpa, circulation 5 times.
The difference of embodiment 5- embodiment 39 and embodiment 2 is shown in Table 1- table 7
The data parameters of 1 embodiment 5- embodiment 9 of table
The data parameters of 2 embodiment 10- embodiment 14 of table
The data parameters of 3 embodiment 15- embodiment 19 of table
The data parameters of 4 embodiment 20- embodiment 24 of table
The data parameters of 5 embodiment 25- embodiment 29 of table
The data parameters of 6 embodiment 30- embodiment 34 of table
The data parameters of 7 embodiment 35- embodiment 39 of table
Embodiment 40
Finasteride gelling agent
1g carbomer 934 is taken, is added in 9g purified water under stiring, sodium sulfite and propylene glycol stirring and dissolving is added,
Triethanolamine is added dropwise, gel carrier is made；Gel is added in Finasteride lipid nano particle prepared by embodiment 2 under stiring
In carrier, stir evenly up to Finasteride gelling agent.Gained gel has the formula shown in table 8.
The prescription of 8 Finasteride gelling agent of table
Embodiment 41
Finasteride cream
By 7g octadecyl alcolol, 3g glycerin monostearate, 2g stearic acid, 5g atoleine, 3g albolene, it is heated to 80-
85 DEG C (oily phase)；Finasteride lipid nano particle prepared by embodiment 2 is heated to 80-85 DEG C under stiring；It is stirring
Water phase is added in oily phase under the conditions of mixing, emulsification is slowly cooled to room temperature to get Finasteride cream.
The prescription of 9 Finasteride cream of table
Embodiment 42
Finasteride lipid nano particle preparation without gel component
By 0.15g Finasteride, 2g soybean lecithin, 5g butyl oleate, 1.2g PLURONICS F87,12g polyethylene glycol 400,
0.06g peppermint oil and the mixing of 79.59g water, with the mixing speed of 1000rpm, stir 5min, using high pressure under the conditions of 10 DEG C
Homogenizer recycles 5 times under the conditions of pressure 7MPa, obtains the Finasteride lipid nanometer preparation without gel component, particle size range
In 10nm-30nm, particle size range 10nm-30nm after being placed at room temperature for 12 months.
The prescription of Finasteride lipid nano particle preparation of the table 10 without gel component
| Ingredient | Dosage g |
| Finasteride | 0.15 |
| Butyl oleate | 5 |
| PLURONICS F87 | 1.2 |
| Polyethylene glycol 400 | 12 |
| Soybean lecithin | 2 |
| Peppermint oil | 0.06 |
| Purified water | 79.59 |
Comparative example 1
Finasteride poly lactide-glycolide acid (PLGA) nanoparticle
The Finasteride for weighing 0.4gPLGA and 0.05g is dissolved in 2mL methylene chloride, is refrigerated, as oily phase O, will be contained 1%
The solution of Nacl and 1%PVA is as water phase W.Under 10 DEG C of condition of ice bath, mutually slowly poured into oily in water phase, in ultrasonic power
Ultrasound 10min forms oil in water emulsion under the conditions of 200W, and 40 DEG C of revolving 15min solidifications are to get Finasteride PLGA nanoparticle.Grain
Diameter range is 100-500nm or so, and partial size is larger, and after being placed at room temperature for for 24 hours, has precipitating to generate, show its physical stability compared with
Difference.
Comparative example 2
Finasteride albumin nano granular
Ox blood albumin 250mg is taken to add in the buffered saline buffer that 10mL pH is 6.6, ultrasonic dissolution, as water phase；
It weighs 10mg Finasteride to be dissolved in 2mL methylene chloride as oily phase, under 10 DEG C of condition of ice bath, under high-speed stirred (10000rpm)
Oil is mutually slowly added in water phase, 3min is emulsified；Ultrasound 5min formation oil in water emulsion under the conditions of ultrasonic power 200W, 30 DEG C
15min solidification is rotated to get Finasteride albumin nano granular.Particle size range is placed at room temperature for 7 days within the scope of 160-250nm
Afterwards, partial size increases within the scope of 160-1000nm, and has Precipitation, shows that its physical stability is poor.
Embodiment 43
Finasteride lipid nanometer Formulation Skin permeability and delay performance evaluation
15 kunming mices, male, 20 ± 2g, Southern Yangtze University's Experimental Animal Center provide, and set experimental situation and raise 4 days
Afterwards, back of mice skin is lost hair or feathers with depilatory agent, clear water is cleaned, and after continuing raising for 24 hours, is put to death, is separated skin of back, removes skin
Lower fat, is cleaned spare with physiological saline.
Dialysis experiment is carried out using Franz diffusion cell, upper storage reservoir is cylindric release pond, and lower pond is coniform reception tank.It will
The skin of diameter 3cm is fixed between release pond and reception tank, and corium side is in contact with acceptable solution.The connection of reception tank side takes
Sample pipe is used for sampling, fluid infusion.Enter 16mL physiological saline into reception tank, is in close contact acceptable solution and skin.By that non-hero
Amine lipid nano particle gelling agent (A group is prepared referring to 40 the method for the present embodiment), Finasteride lipid nano particle cream (B
Group, referring to 41 the method for the present embodiment prepare), Finasteride lipid nano particle (the C group, referring to this implementation containing gel component
The preparation of 2 the method for example), Finasteride lipid nano particle preparation without gel component (D group, the side referring to described in embodiment 42
Method preparation) and 0.25% Finasteride regular solution agent, (control group, 15% ethyl alcohol and 15% aqueous solution of propylene glycol are as matrix)
It is uniformly applied to release pond side skin surface (A group, B group, C group, the dosage of D group and control group are 0.3mg), sets 37 DEG C of constant temperature
In water-bath, 200rpm is incubated for.Respectively at 1,3,6,9,12 and 24 hour, 0.5mL acceptable solution is drawn in reception tank side, and supplement
0.5mL fresh physiological salt water.Measure Finasteride concentration in receiving liquid.It is as shown in Figure 3 to accumulate penetration curve.
After dialysis experiment, skin is collected, distilled water flushing 10 times, surface is removed and smears preparation.0.5mL distillation is added
Water is homogenized using tissue refiner, the precision 200 above-mentioned homogenates of μ L of absorption, 400 μ L acetonitriles of addition, vortex 10min,
12000rpm is centrifuged 10min, using Finasteride concentration in high effective liquid chromatography for measuring supernatant, evaluates Finasteride lipid
The skin anelasticity of nanometer formulation.Finasteride skin hold-up is seeped as shown in figure 4, calculating different groups of skin cumulative simultaneously
Saturating percentage, as shown in table 11.
From figure 3, it can be seen that each test group percutaneous permeability is from low to high successively are as follows: control group <be free of gel component
The Finasteride lipid nano particle < Finasteride lipid nano particle containing gel component < Finasteride lipid nano particle gelling agent <
Finasteride lipid nano particle cream.
Figure 4, it is seen that each test group skin anelasticity is from low to high successively are as follows: control group <be free of gel component
The Finasteride lipid nano particle < Finasteride lipid nano particle containing gel component < Finasteride lipid nano particle gelling agent <
Finasteride lipid nano particle cream.
Table 11 is percutaneous permeability result.
11 skin cumulative Percent penetration of table
The result shows that the Finasteride lipid without gel component is received compared with Finasteride regular solution (control group)
The grain of rice (D group) has higher percutaneous permeability and anelasticity；Gel component (C) is added into Finasteride lipid nano particle
Afterwards, the percutaneous permeability and anelasticity of Finasteride be can further improve；Finasteride lipid nano particle is prepared into gelling agent
After (A group) and cream (B group), compared with C group, the percutaneous permeability and anelasticity of Finasteride can further improve.
Embodiment 44
60 kunming mices, male, 20 ± 2g, Southern Yangtze University's Experimental Animal Center provide, and set experimental situation and raise 4 days
Afterwards, by mouse subcutaneous injection testosterone handle two weeks, two weeks after, with depilatory cream by experiment mice carries out back lose hair or feathers handle so as to
Treatment.Above-mentioned mouse is randomly divided into six groups (A, B, C, D, E and F groups), every group 10.Respectively at back of mice (diameter 1cm)
Smear 0.1mL physiological saline (A group), 0.25% agent of Finasteride regular solution (15% ethyl alcohol and 15% propylene glycol solution, B
Group), Finasteride Finasteride lipid nano particle gelling agent (referring to 40 method of the present embodiment prepare, C group), Finasteride lipid
Nanoparticle cream (being prepared referring to 41 method of the present embodiment, D group), the Finasteride lipid nano particle group containing gel component
(preparing referring to 2 method of the present embodiment, E group) and Finasteride lipid nano particle group without gel component are (referring to embodiment 42
Method preparation, F group), wherein B group, C group, D group, the dosage of E group and F group be 0.15mg/ only, dosage period is one day 2
Secondary, the 1st, 2,3,4,8,12 and 16 week observation hair growth situation, measurement increase number of hairs and hair increase thickness after administration
Degree.Rank scores (1: grey black are carried out according to hair growth situation；2: visible undercoat hair；3: sparse long hair；4: dense to become mildewed
Hair；5: hair growth restores completely).Treatment results are as shown in table 12 and Fig. 5.
The hair recovery capability result of the different therapeutic modalities of table 12 compares
As can be seen from Table 12, each test group increases number of hairs and hair increases the effect of thickness from low to high successively
Are as follows: physiological saline (A group) < Finasteride regular solution agent (B the group) < Finasteride lipid nano particle (F without gel component
Group) < Finasteride the lipid nano particle (E group) containing gel component < Finasteride lipid nano particle gelling agent (C group) < that non-hero
Amine lipid nano particle cream (D group).
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To make various changes or modifications to the present invention, such equivalent forms equally fall within model defined by the application the appended claims
It encloses.
Claims (10)
1. a kind of Finasteride lipid nano particle, which is characterized in that the lipid nano particle includes:
(1) Finasteride；
(2) pharmaceutically acceptable nanoparticle auxiliary material, comprising:
(a) matrix material；
(b) emulsifier；
(c) assistant for emulsifying agent；
(d) oily phase；With
(e) water phase；
The partial size of the Finasteride lipid nanometer preparation is 1-1000nm.
2. lipid nano particle as described in claim 1, which is characterized in that the content of the Finasteride is 0.0001-5 weight
Part, preferably 0.01-0.3 parts by weight；And/or
The content of the matrix material is 0.1-20 parts by weight, preferably 0.5-5 weight；And/or
The content of the emulsifier is 0.01-50 parts by weight, preferably 0.5-20 parts by weight, more preferably 0.5-10 parts by weight, more
Preferably 0.5-5 parts by weight；And/or
The content of the assistant for emulsifying agent is 1-60 parts by weight, preferably 10-20 parts by weight；And/or
The content of the oil phase is 0.1-60 parts by weight, preferably 0.2-10, more preferably 2-10 parts by weight；And/or
The content of the water phase is 10-90 parts by weight, preferably 60-90 parts by weight.
3. lipid nano particle as described in claim 1, which is characterized in that the pharmaceutically acceptable nanoparticle auxiliary material is also
Including gel component；
The gel component is selected from the group: glycerol, poloxamer, carboxymethyl cellulose, collagen, hyaluronic acid, xanthan gum,
The sub- glue of gelatin, Arabic gum, sand sagebrush (Artemisia filifolia), or combinations thereof.
4. lipid nano particle as described in claim 1, which is characterized in that the emulsifier is selected from the group: Arabic gum, west
Bassora gum, gelatin, fatty acid salt, higher aliphatic alcohol sulfuric ester, higher fatty acid salt, fatty glyceride, fatty acid sorbitan,
Polysorbate, poloxamer, polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether, polyoxyethylene alcohol, polyoxyethylene caster
Oil, sodium taurocholate, albumin, beeswax, or combinations thereof.
5. a kind of Finasteride preparation, which is characterized in that the preparation includes Finasteride lipid as described in claim 1
Nanoparticle and pharmaceutically acceptable carrier.
6. preparation as claimed in claim 5, which is characterized in that the Finasteride preparation is Finasteride lipid nano particle
Gelling agent, the Finasteride lipid nano particle gelling agent include Finasteride lipid nano particle as described in claim 1,
With pharmaceutically acceptable gel carrier；
Wherein, the gel carrier includes one or more gel-type vehicles selected from the group below: carbomer, glycerol, poloxamer,
Carboxymethyl cellulose, collagen, hyaluronic acid, xanthan gum, gelatin, the sub- glue of Arabic gum, sand sagebrush (Artemisia filifolia), or combinations thereof.
7. preparation as claimed in claim 5, which is characterized in that the Finasteride preparation is Finasteride lipid nano particle
Cream, the cream include Finasteride lipid nano particle as described in claim 1 and pharmaceutically acceptable cream
Cream carrier；
Wherein, the pharmaceutically acceptable emulsifiable paste carrier includes one or more emulsifiable paste matrixes selected from the group below: advanced rouge
Fat acid, paraffin, beeswax, higher aliphatic, vaseline, vegetable oil, soaps, lauryl sodium sulfate, polyalcohol aliphatic ester,
Poly yamanashi esters, monoglyceride, polyoxyethylene ether, or combinations thereof.
8. a kind of method for preparing lipid nano particle as described in claim 1, which is characterized in that the method includes step
It is rapid:
Finasteride, matrix material, emulsifier, assistant for emulsifying agent, oil are mutually mixed with water phase, Finasteride lipid nanometer is obtained
Grain.
9. the purposes of a kind of lipid nano particle as described in claim 1 or Finasteride preparation as claimed in claim 7, special
Sign is, is used to prepare prevention and/or hair growth or promotees hair tonic medicament.
10. it is a kind of for prevent and/or hair growth or growth-promoting hair method, which is characterized in that give required object such as right
It is required that lipid nano particle described in 1 or Finasteride preparation as claimed in claim 7.
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| CN111329832A (en) * | 2020-02-08 | 2020-06-26 | 中山大学 | Nanometer lipid carrier microneedle for treating alopecia and application thereof |
| CN115400085A (en) * | 2022-09-02 | 2022-11-29 | 南昌大学 | Finasteride lipid vesicles and preparation method and application thereof |
| CN116687993A (en) * | 2023-06-28 | 2023-09-05 | 无锡市妇幼保健院 | Radix arnebiae and safflower cream and preparation method thereof |
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| CN111329832B (en) * | 2020-02-08 | 2021-07-16 | 中山大学 | Nanometer lipid carrier microneedle for treating alopecia and application thereof |
| CN115400085A (en) * | 2022-09-02 | 2022-11-29 | 南昌大学 | Finasteride lipid vesicles and preparation method and application thereof |
| CN116687993A (en) * | 2023-06-28 | 2023-09-05 | 无锡市妇幼保健院 | Radix arnebiae and safflower cream and preparation method thereof |
| CN116687993B (en) * | 2023-06-28 | 2024-04-16 | 无锡市妇幼保健院 | Radix arnebiae and safflower cream and preparation method thereof |
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