CN101917959B - Peptide nanoparticles and its purposes - Google Patents
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- CN101917959B CN101917959B CN200780049796.8A CN200780049796A CN101917959B CN 101917959 B CN101917959 B CN 101917959B CN 200780049796 A CN200780049796 A CN 200780049796A CN 101917959 B CN101917959 B CN 101917959B
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- 229910052759 nickel Inorganic materials 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000000050 nutritive Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 235000013348 organic food Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
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- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 244000045947 parasites Species 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
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- 230000036231 pharmacokinetics Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L phosphate Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920001306 poly(lactide-co-caprolactone) Polymers 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 108091008117 polyclonal antibodies Proteins 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 239000005056 polyisocyanate Substances 0.000 description 1
- 229920000023 polynucleotide Polymers 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
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- 238000002600 positron emission tomography Methods 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003405 preventing Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000529 probiotic Effects 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
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- 239000000583 progesterone congener Substances 0.000 description 1
- 108010015796 prolylisoleucine Proteins 0.000 description 1
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 1
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- 238000000746 purification Methods 0.000 description 1
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 1
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- 239000004576 sand Substances 0.000 description 1
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- 239000010703 silicon Substances 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
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- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000037335 skin penetration Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- MAKUBRYLFHZREJ-JWBQXVCJSA-M sodium;(2S,3S,4R,5R,6R)-3-[(2S,3R,5S,6R)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylate Chemical compound [Na+].CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@H](O)[C@H]1O MAKUBRYLFHZREJ-JWBQXVCJSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
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- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 201000009594 systemic scleroderma Diseases 0.000 description 1
- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine(1+) Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- 108010061238 threonyl-glycine Proteins 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 230000002936 tranquilizing Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
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- 230000014621 translational initiation Effects 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- IOUPEELXVYPCPG-UHFFFAOYSA-N val-gly Chemical compound CC(C)C(N)C(=O)NCC(O)=O IOUPEELXVYPCPG-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 108010011876 valyl-glycyl-valyl-alanyl-prolyl-glycine Proteins 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium(0) Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 150000003697 vitamin B6 derivatives Chemical class 0.000 description 1
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- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
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- 239000011712 vitamin K Substances 0.000 description 1
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- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N α-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
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Abstract
The present invention provides the nanoparticle compositions including one or more peptides.The present invention can realize described peptide transdermal transfer and without carry out peptide modification or without to skin use chemically or mechanically grind or destroy.
Description
Related application
Subject application advocates U.S. Provisional Patent Application case filed in December in 2006 1 day according to 35U.S.C. § 119 (e)
The priority of U.S.S.N.60/872,206 (" ' 206 application case ").The full content of ' 206 application cases is herein incorporated by reference
Herein.
Background technology
Show that peptide has useful cosmetic and treatment effectiveness for skin.In experimental model, show small peptide (length
At most 30 aminoacid) stimulate the collagen growth in Skin Cell epimatrix, this outward appearance that can improve skin and improvement
The healing of damaged skin (sheet mountain (Katayama) et al., 1993, journal of biological chemistry (J.Biol.Chem.), 268:9941;With
The mode quoted is incorporated herein).The most having shown that modified peptide reduces wrinkled appearance by regulatory enzyme, these enzymes affect skin
Skin underlying muscle promotes muscle contraction that wrinkle formed (road ripple (Lupo), 2005, skin surgery (Dermatol.Surg.),
31:832;It is incorporated herein by reference).
But, by peptide through epidermal barrier (horny layer) transdermal transfer to biological agent site, such as extracellular matrix or
Underlying muscle, the past always realize these peptides in mankind's body potential cosmetic and treatment effectiveness a great problem (Robinson
(Robinson) et al., 2005, international cosmetic Scientific Magazine (International J.Cosmetic Science) 27:
155;It is incorporated herein by reference).In order to realize the transmission of peptide transdermal transfer in mankind's body, it is necessary to by adding
Such as (but not limited to) the chemical part such as acetyl group and/or palmityl come chemical modification peptide (Robinson (Robinson) et al.,
On seeing).These chemical modifications are disadvantageous, because it is costly and time-consuming, this negatively affects the work of the product containing these peptides
Industry produces.The chemical modification of peptide also can be incorporated into the ability (example with bioactive cell receptor site by reduction peptide
As by steric influence) and reduce the biological activity of peptide so that it is the most effective.The most effective peptide will be not enough to reality
Now make up or therapeutic purposes.Comparatively speaking, needs are realized its institute with high level administration by the most effective peptide
Needing biological effect (if effect is it is also possible to exist), this will be cost unfavorable factor for the commercial production of product.
Summary of the invention
The present invention describes and incorporates the nanoparticle of the most modified small peptide (2 to 30 amino acid longs), these without
The small peptide modified is biological activity in skin (including epidermis and corium), subcutaneous tissue (including fatty tissue) and proximal muscles
Agent.
The nanoparticle of the present invention can be applied in individual's skin.In certain embodiments, the nanoparticle of the present invention is real
The existing peptide transdermal transfer being incorporated to is to described individuality.
The nanoparticle of the present invention can be applied on skin as simple suspension or dispersion, or with a kind of or
More than one excipient mix and are prepared as composite, such as (but not limited to) toner/smoothing toner, nutritive water, clean skin liquid, cleansing cream, breast
Liquid, milky lotion, massage cream, emollient cream, end adornment liquid, lip pomade, facial film or face glue, cleaning agent composite (such as shampoo, purificant,
Bath gel, hair conditioner and soap) and dermatological composition (such as lotion, ointment, gel, emulsifiable paste, paster and spraying).
Therefore, the present invention is provided to system and the compositions of the most modified peptide of transdermal transfer.The many of the present invention is excellent
One of point be can transmit peptide and without injection without mechanically or chemically grinding or transforming skin.Further advantage includes can profit
With the most modified peptide, thus simplify cosmetic of the present invention and/or the production of pharmaceutical formulation and reduce production cost, and retaining
The biological activity of peptide.
Accompanying drawing explanation
Fig. 1 is the histologic analysis of the mice processed with peptide nanoparticles.Show the skin with the dyeing of Mason's trichrome staining
The microphotograph of skin tissue.Matched group (the nanoparticle composite without pentapeptide) Mean histology score is 2.33, the highest can
Can score 4.Process group (the nanoparticle composite containing pentapeptide) Mean histology score is 3.67, highest possible score 4.
Detailed description of the invention
Definition
Grind: as used herein, term " grinds " and refers to transform, destroy, remove or damage any of skin surface
Method.In certain embodiments, grinding refers to transform, destroy, remove or damage the mechanical means of skin surface.Implement at some
In example, grind and refer to transform, destroy, remove or damage the chemical method of skin surface.Only give a few examples, such as scrubbing cream
(exfoliant), the medicament such as particulate (such as magnesium or aluminum particulate), acid (such as 'alpha '-hydroxy acids or beta-hydroxy acid), alcohols may draw
Rise and grind.In general, it is contemplated that such as those (such as) are by Duonowan (Donovan) (such as United States Patent (USP) publication 2004/
009180 and 2005/175636 and PCT Publication case WO 04/06954;All it is incorporated herein by reference) and Gray's strategic point
Nurse (Graham) (such as United States Patent (USP) 6,939,852 and United States Patent (USP) publication 2006/093624;The most by reference
Be incorporated herein) etc. described penetration enhancers can cause grinding.Certainly, it will be understood by one of ordinary skill in the art that specific
There is or may cause when combining one or more other medicaments grinding in medicament, but in varied situations with finite concentration
Grinding may not be caused.Therefore, whether certain material is that " grinding agent " need to depend on the circumstances.Grinding can be by the technology of art
Personnel are easily assessed, such as by the observation to the general red of skin or stimulated and/or to showing cuticular transformation, breaking
Bad, remove or the histological examination of skin of erosion.
Aminoacid: as used herein, term " aminoacid " may be incorporated into appointing in polypeptide chain its broadest referring to
What compound and/or material.In certain embodiments, aminoacid has universal architecture H2N-C(H)(R)-COOH.Real at some
Execute in example, the aminoacid that aminoacid is naturally-occurring.In certain embodiments, aminoacid is synthesizing amino acid;Implement at some
In example, aminoacid is D-aminoacid;In certain embodiments, aminoacid is l-amino acid." standard amino acid " refers to natural depositing
Peptide in any one in common 20 kinds of standard l-amino acids." non-standard amino acid " refers in addition to standard amino acid
Any aminoacid, does not consider that it is with synthesis mode preparation or to obtain from natural origin.Peptide includes carboxyl and/or amino end
The methyl that its activity can not had a negative impact by changing the circulating half-life of peptide by terminal amino acid at interior aminoacid
Change, amidatioon, acetylation and/or with other chemical group replace modify.But, as described herein, the special pin of the present invention
To " the most modified peptide ", the meaning be not yet through chemical modification to promote or realize the peptide of transdermal transfer.Aminoacid may participate in
Disulfide bond.Term " aminoacid " can exchange the aminoacid using and can referring to free amino acid and/or peptide with " amino acid residue "
Residue.It is clear that it does not refer to free amino acid from the context using this term, it is simply that refer to the residue of peptide.
Animal: as used herein, term " animal " refers to any member of regnum animale.In certain embodiments, " dynamic
Thing " refer to be in the mankind of any stage of development.In certain embodiments, " animal " refers to be in the inhuman of any stage of development
Class animal.In certain embodiments, described non-human animal is mammal (such as rodent, mice, rat, rabbit, monkey
Son, Canis familiaris L., cat, sheep, cattle, primate and/or pig).In certain embodiments, animal include, but is not limited to suckling move
Thing, birds, reptile, Amphibian, Fish and/or anthelmintic.In certain embodiments, animal can be transgenic animal,
Genetic engineering animal and/or cloned animal (clone).
About: as used herein, term " about " refers to be similar to when being applied to one or more values paid close attention to
Value in described reference value.In certain embodiments, unless otherwise prescribed or by context obviously (except described number will
Exceed the 100% of probable value), otherwise term " about " refers to the either direction (being more than or less than) in described reference value
25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%,
5%, 4%, 3%, 2%, 1% or less than 1% interior value scope.
Bioactivator: as used herein, phrase " bioactivator " refers in biosystem and/or organism
Active any material.For example, when to organism administration, described organism is had the material quilt of biological effect
It is considered as that there is biological activity.In a particular embodiment, when protein or polypeptide have biological activity, described protein or polypeptide
Total protein or at least one bioactive part of polypeptide be commonly called " biological activity " part.
Botulinum toxin (Botulinum toxin): as used herein, term " botulinum toxin " refers to by bacillus botulinus
Any neurotoxin that (Clostridium botulinum) produces.Unless otherwise directed, described god contained in the most described term
Through toxin reservation suitable active (such as muscle relaxant activities) fragment or part (such as light chain and/or heavy chain).As herein
Used in, botulinum toxins serotypes A, B, C, D, E, F and G contained in phrase " botulinum toxin ".As used herein, meat poisoning poison
Element is also covered by botulinum toxin complex (i.e., such as 300,600 and 900kD complex) and purified (i.e., such as separated)
Botulinum toxin (i.e., e.g., from about 150kD)." purified botulinum toxin " is defined as and the albumen including botulinum toxin complex
The botulinum toxin that the other oroteins of matter separates or is substantially separated.The purity of purified toxin can more than 95% and purity excellent
Choosing is more than 99%.It will be understood by one of ordinary skill in the art that the present invention is not limited to the botulinum toxin of any particular source.Citing
For, botulinum toxin used according to the invention can separate from bacillus botulinus, can chemically synthesize, and can recombinate generation (i.e.,
In the host cell in addition to bacillus botulinus or organism) etc..
Characteristic: as used herein, " characteristic " of phrase material is and relevant complete thing in the broadest sense
Matter has the part of a certain degree of sequence and/or structural integrity and/or at least one functional character.For example, albumen
" characteristic " of matter or polypeptide be the continuous amino acid section containing the feature jointly becoming protein or polypeptide or one group continuous
The part of aminoacid section.In certain embodiments, each described continuous segment generally will containing at least 2,5,10,15,
20 or 20 with upper amino acid.In general, characteristic is complete to relevant in addition to sequence identity specified above
Protein has the part of at least one functional character.In certain embodiments, characteristic can have biological activity.
Hydrophilic: as used herein, the material that " hydrophilic " material is soluble in polar solvent.Implement at some
In example, hydroaropic substance can temporarily and polar solvent bond.In certain embodiments, hydroaropic substance is by hydrogen bond temporarily and pole
Property solvent bond.In certain embodiments, polar solvent is water.In certain embodiments, hydroaropic substance can be ion-type.
In certain embodiments, hydroaropic substance can be nonionic.In certain embodiments, with oil, non-polar solven or dredge
Comparing in aqueous solvent, hydroaropic substance can be more soluble in water, polar solvent or hydrophilic solvent.In some embodiments
In, compared with in water, polar solvent or hydrophilic solvent, hydroaropic substance can be less susceptible to be dissolved in oil, non-polar solven or
In hydrophobic solvent.In certain embodiments, a kind of material is hydrophilic relative to another material, because it is than another material
It is more soluble in water, polar solvent or hydrophilic solvent.In certain embodiments, a kind of material is hydrophilic relative to another material
Property, because it is less susceptible to be dissolved in oil, non-polar solven or hydrophobic solvent than another material.
Hydrophobicity: as used herein, the material that " hydrophobicity " material is soluble in non-polar solven.Real at some
Executing in example, lyophobic dust is repelled by polar solvent.In certain embodiments, polar solvent is water.In certain embodiments,
Lyophobic dust is nonpolar.In certain embodiments, compared with in water, polar solvent or hydrophilic solvent, hydrophobicity
Material can be more soluble in oil, non-polar solven or hydrophobic solvent.In certain embodiments, with oil, non-polar solven
Or hydrophobic solvent is compared, lyophobic dust can be less susceptible to be dissolved in water, polar solvent or hydrophilic solvent.Real at some
Executing in example, a kind of material is hydrophobic relative to another material, because it is more soluble in oil, non-polar solven than another material
Or in hydrophobic solvent.In certain embodiments, a kind of material is hydrophobic relative to another material, because it is than another thing
Matter is the most soluble in water, in polar solvent or hydrophilic solvent.
With ... combining: as used herein, phrase " combine transmit " refers to two or more material or medicament
Common transmission.Specifically, according to the nanoparticle of the present invention, the referenced herein bioactivator of described phrase and the present invention
And/or nanoparticle compositions uses when transmitting together.When a kind of material or medicament and nanoparticle and/or combinations of nanoparticles
During thing combination;When by nanoparticle-encapsulated or surrounding completely;When being embedded in nanoparticle micelle film;And/or and nanoparticle
When the outer surface of micelle film associates, described material or medicament are combined transmission with nanoparticle.It is intended to and nanoparticle and/or nanoparticle
Subgroup compound combine the material of transmission or medicament may with or may not with described nanoparticle and/or nanoparticle compositions altogether
Valence link joins.Be intended to be combined the material transmitted with the nanoparticle of the present invention and/or nanoparticle compositions or medicament may pass through or
Described nanoparticle and/or nanoparticle compositions may not be attached to by absorption affinity.
Separated: as used herein, term " separated " refers to following material and/or entity: (1) with primiparity
Relative at least some Component seperation (no matter in nature and/or in experimental situation) time raw;And/or (2) pass through
Artificially generated, prepare and/or manufacture.Separated material and/or entity can be with at least about 10%, about 20%, about 30%, about
40%, other Component seperation that about 50%, about 60%, about 70%, about 80%, about 90% or more than 90% are the most relevant to it.
In certain embodiments, the purity of separated material and/or entity more than 90%, 91%, 92%, 93%, 94%, 95%,
96%, 97%, 98%, 99%.
Microfluidization: as used herein, the meaning of term " microfluidization " is exposed under high shear force.At some
In embodiment, described in be exposed under high shear force be to get off realization by being exposed to high pressure;In certain embodiments, described high pressure
In the range of about 15,000psi to about 26,000psi.In certain embodiments, being exposed to described under high shear force is to pass through
Cavitation (cavitation) realizes.In certain embodiments, it is all by making sample pass through for being exposed to described under high shear force
Such as microfluidization instrument(micro-fluidic company (Microfluidics Corporation)/MFIC company
(MFIC Corporation)) etc. instrument or be applicable to form other similar device of homogeneous nanoparticle compositions and come real
Existing.In some embodiments of the invention, sample miniflow is made by being exposed under high shear force the time of less than about 10 minutes
Body.In certain embodiments, the described time is less than about 9,8,7,6,5,4,3,2 or 1 minutes.In certain embodiments, the time
In the range of about 1-2 minute.In certain embodiments, the time is about 30 seconds.In some embodiments of the invention, by list
The secondary high shear force that is exposed to gets off to make sample " microfluidization ";Described embodiment is referred to as " one way " microfluidization.
Nanoparticle: as used herein, term " nanoparticle " refers to have less than 1000 nanometers (nm) diameter
Any particle.In certain embodiments, nanoparticle such as National Science Foundation (National
ScienceFoundation) defined, be there is the diameter less than 300nm.In certain embodiments, nanoparticle has such as U.S.
NIH of state (National Institutes of Health) is defined, less than the diameter of 100nm.At some
In embodiment, nanoparticle is micelle, because it comprises the sealed compartments separated by micelle film with bulk solution." micelle film "
Comprise and assemble encirclement seal clearance or the amphiphilic entity of compartment (such as, to define inner chamber).
Nanoparticle compositions: as used herein, term " nanoparticle compositions " refers to receive containing at least one
Any material of rice corpuscles.In certain embodiments, nanoparticle compositions is homogeneous one group nanoparticle.Implement at some
In example, nanoparticle compositions is dispersion liquid or emulsion.In general, when combining the immiscible material of at least two, formed
Dispersion liquid or emulsion." oil-in-water " dispersion liquid is that oily particle (or hydrophobicity or nonpolar) is scattered in aqueous dispersion medium
Dispersion liquid." Water-In-Oil " dispersion liquid is that aqueous (or hydrophilic or polarity) particle is scattered in the dispersion liquid in oiliness disperse medium.
It will be understood by one of ordinary skill in the art that dispersion liquid can be formed by the immiscible medium of any two and is not strictly limited to aqueous
Medium and the combination of oil medium.Therefore, term " disperse medium " is widely used in any disperse medium, although generally mentioning
" aqueous " and " oiliness " classification.In certain embodiments, nanoparticle compositions is nanoemulsions.In certain embodiments, receive
Nanoparticle composition comprises micelle.In particular embodiments, nanoparticle compositions comprises such as Shen on November 30th, 2007
The PCT application case PCT/ of entitled " amphiphilic entity nanoparticle (AMPHIPHILICENTITY NANOPARTICLES) " please
Amphiphilic entity nanoparticle described in No. US07/___ (being incorporated herein by reference).In certain embodiments, receive
Nanoparticle composition is stable.In certain embodiments, nanoparticle compositions includes that one or more are intended to and nanometer
Particle combines the bioactivator of transmission.
Nutrient and healthcare products (Nutraceutical): as used herein, term " nutrient and healthcare products " refers to provide doctor
, healthy or any material of biological interest.In certain embodiments, nutrient and healthcare products can be with diseases prevention.In some embodiments
In, nutrient and healthcare products can provide basal nutrient to be worth.In certain embodiments, nutrient and healthcare products are of food or food
Point.In certain embodiments, nourishing healthy agent can be a separated nutrient of class, dietary supplement, vitamin, mineral
Matter, medical herbs, condensed food, dietetic food (healing food), genetic engineering food and processed food.Nutrient and healthcare products also may be used
It is referred to as " phytochemistry food " or " functional food ".
Pre-composition: as used herein, term " pre-composition " refers to be used subsequently to produce the nanoparticle according to the present invention
Any combination of the component of subgroup compound.For example, pre-composition is to produce receiving according to the present invention when subjected to high shear forces
Any group of composition of rice corpuscles.In certain embodiments, pre-composition contains two or more immiscible solvent.One
In a little embodiments, pre-composition contains the component being self-assembled into nanoparticle.In certain embodiments, pre-composition contains and is self-assembled into
The component of micelle.In certain embodiments, pre-composition contains " amphiphilic entity nanoparticle entitled as filed in 30 days November in 2007
Son (AMPHIPHILIC ENTITY NANOPARTICLES) " PCT application case the PCT/US07/___________th (to draw
Mode be incorporated herein) described in one or more amphiphilic entities.In certain embodiments, pre-composition contains one
Plant or more than one the most modified peptides;In certain embodiments, pre-composition contains at least one other bioactivator.One
In a little embodiments, pre-composition is stirred, mixes and/or stir;In certain embodiments, will premix before standing high shear force
Thing stirs, mixes and/or stir.In certain embodiments, pre-composition comprise at least one dissolve component (that is, at least one
Component in solution form);In embodiment some described, pre-composition is made to stand high shear force after realizing described dissolving.
Pure: as used herein, if a kind of material and/or entity are substantially free of other component, then it is
" pure ".For example, the preparation containing greater than about 90% predetermined substance and/or entity is generally viewed as pure preparation.At some
In embodiment, the purity of material and/or entity be at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or
99%.
Shearing force: as used herein, term " shearing force " refers to and is perpendicular to the power of material face comparatively speaking, parallel
Power in material face.In certain embodiments, compositions is made to be exposed to high shear force to produce homogeneous nanoparticle compositions.
In art, known any method can be used for producing high shear force.In certain embodiments, cavitation is used to produce high shear
Power.In certain embodiments, high pressure homogenization is used to produce high shear force.Alternatively or additionally, can be by being exposed to high pressure (such as
About 15,000psi) get off to grant high shear force.In certain embodiments, described high pressure about 18,000psi to about 26,
In the range of 000psi;In certain embodiments, it is about 20, and 000psi to about 25, in the range of 000psi.Implement at some
In example, use microfluidization instrumentProcessing means (micro-fluidic company/MFIC company) or other similar device
Produce high shear force.Microfluidization instrumentBy making compositions, at full speed (usual scope is processing means
50m/s-300m/s) accelerate by microchannel (being generally of the size of about 75 microns) so that nano-scale range will be reduced in size to
High pressure and gained high-rate of shear are provided.Along with fluid leaves microchannel, it forms jet, with the jet from relative microchannel
Collision.In the channel, fluid experience high shear (up to 10 of high several orders of magnitude than routine techniques7l/s).Jet collision makes
Pattern of sub-micron level mixes.Therefore, in said device, high shear and/or impact can realize particle diameter reduction and heterogeneous mixing.
In some embodiments of the invention, the time that sample is exposed under high shear force less than about 10 minutes is made.In some embodiments
In, the described time is less than about 9, about 8, about 7, about 6, about 5, about 4, about 3, about 2 or about 1 minute.In certain embodiments, the time exists
In the range of about 1 to about 2 minutes or shorter time;In certain embodiments, the time is about 30 seconds.Some enforcements in the present invention
In example, get off to make sample " microfluidization " by single exposure in high shear force;Described embodiment is referred to herein as " single
Journey " microfluidization.
Little molecule: in general, " little molecule " is interpreted as being smaller in size than about 5 kilodaltons (Kd) in the art
Organic molecule.In certain embodiments, little molecule is less than about 3Kd, about 2Kd or about 1Kd.In certain embodiments, little molecule is little
In about 800 dalton (D), about 600D, about 500D, about 400D, about 300D, about 200D or about 100D.In certain embodiments, little
Molecule is non-polymeric molecule.In certain embodiments, little molecule is not protein, peptide or aminoacid.In certain embodiments, little
Molecule is not nucleic acid or nucleotide.In certain embodiments, little molecule is not saccharide or polysaccharide.
Individual: as used herein, term " individual " or " patient " refer to can the compositions (such as) of the administration present invention
For testing, diagnose, prevent and/or any organism of therapeutic purposes.Typical individual include animal (such as, mammal, all
Such as mice, rat, rabbit, non-human primate and the mankind;Insecticide;Anthelmintic;Deng).
Substantially: as used herein, term " substantially " refers to represent all or close to four corner or degree
The feature paid close attention to or the qualitative condition of characteristic.Field of biology skilled person will appreciate that biology and chemical phenomenon are little
(if it occur that mistake) reaches complete and/or proceeds to completely or realize or avoid absolute results.Therefore, term " substantially " exists
Herein for catching potential completeness shortage intrinsic in many biologys and chemical phenomenon.
Stable: the meaning when being applied to nanoparticle compositions herein " stablized " in term is institute within a period of time
State compositions and maintain one or more aspects (such as size range and/or particle are distributed) of its physical arrangement.At this
In some bright embodiments, stable nanoparticle compositions is to make mean diameter, maximum particle diameter, particle size range and/or particle diameter
Distribution (that is, exceeding specified size and/or the particle percentage beyond specified size scope) maintains the nanoparticle of a period of time
Compositions.In certain embodiments, the described time is at least about 1 hour;In certain embodiments, the time be about 5 hours, about 10
Hour, about one (1) sky, about one (1) week, about two (2) weeks, about one (1) individual month, about two (2) individual months, about three (3) individual months, about four
(4) individual month, about five (5) individual months, about six (6) individual months, about eight (8) individual months, about ten (10) individual months, about 12 (12) individual months, about two
Ten four (24) individual months or longer time.In certain embodiments, the time in about one (1) sky to about 24 (24) individual months, about two
(2) thoughtful about 12 (12) individual months, about two (2) individual months to about five in the range of (5) individual months etc..For example, if making nanometer
Most of nanoparticle that particle composition stands in long term storage, variations in temperature and/or pH value change and colony maintains rule
Diameter (i.e., such as between about 10nm-120nm) in the range of Ding, then nanoparticle compositions is stable.For some
For described colony, major part is greater than about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 96%, about
97%, about 98%, about 99%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, about 99.9% or more than 99.9%.
In some embodiments of the invention, when nanoparticle compositions comprise one or more bioactivators (such as without
The peptide modified) time, if through the appointment time under the set condition specified, the bioactivator in nanoparticle compositions
Concentration is maintained, then compositions is considered stable.
It is substantially free of: when in the nanoparticle compositions of the present invention, the particle of no more than about 50% has beyond regulation model
During the diameter enclosed, described compositions is referred to as " being substantially free of " diameter particle beyond described scope.In certain embodiments,
Particle less than 25% goes beyond the scope.In certain embodiments, less than 20%, 19%, 18%, 17%, 16%, 15%,
14%, the grain of 13%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5% or less than 0.5%
Son has the diameter beyond prescribed limit.
Suffer from: the individuality of " suffering from " disease, disease or condition of illness (such as facial wrinkles) has diagnosed suffers from or represent described disease
Disease, disease or the symptom of condition of illness.
Therapeutically effective amount: as used herein, the meaning of term " therapeutically effective amount " be when to suffer from or susceptible disease,
Be enough to treat the combinations of nanoparticles of the present invention of described disease, disease and/or condition of illness during patient's administration of disease and/or condition of illness
The amount of thing.
Therapeutic agent: as used herein, phrase " therapeutic agent " refer to have when to individual administration response to treatment and/or
Cause any medicament of required biological effect and/or pharmacodynamics effect.
Treatment: as used herein, any administration referring to bioactivator, described bioactivator " treated " in term
Partially or completely alleviate, improve, alleviate, suppress one or more symptoms or the spy of specified disease, disease and/or condition of illness
Levy, postpone described symptom or the outbreak of feature, reduce described symptom or the seriousness of feature and/or reduce described symptom or feature
Incidence rate.Described treatment for not representing the individuality of symptom of relevant disease, disease and/or condition of illness and/or can only represent institute
State the individuality of the early stage symptom of disease, disease and/or condition of illness.Alternatively or additionally, described treatment can for represent relevant disease,
One or more of disease and/or condition of illness determine the individuality of symptom.
Toxic solvent: as used herein, term " toxic solvent " refers to transform, destroys, removes or damage animal
Any material of tissue.As skilled in the art should understand, animal tissue can include living cells, dead cell, extracellular
Substrate, cell connect (cellular junction), biomolecule etc..Only give a few examples, toxic solvent include dimethyl sulfoxide, two
Methylacetamide, dimethylformamide, chloroform, tetramethyl Methanamide, acetone, acetas and alkane.
Homogeneous: when term " homogeneous " referenced herein nanoparticle compositions uses, to refer to that indivedual nanoparticle has
The nanoparticle compositions of the particle diameter size range specified.For example, in certain embodiments, homogeneous nanoparticle subgroup
Compound is that the difference between minimum diameter and maximum gauge is no more than about 600nm, about 550nm, about 500nm, about 450nm, about
400nm, about 350nm, about 300nm, about 250nm, about 200nm, about 150nm, about 100nm, about 90nm, about 80nm, about 70nm, about
The nanoparticle compositions of 60nm, about 50nm or below 50nm.In certain embodiments, the homogeneous combinations of nanoparticles of the present invention
Particle (such as containing the particle of the most modified peptide) in thing has less than about 600nm, about 550nm, about 500nm, about
450nm, about 400nm, about 350nm, about 300nm, about 250nm, about 200nm, about 150nm, about 130nm, about 120nm, about
115nm, about 110nm, about 100nm, about 90nm, about 80nm or 80nm diameter below.In certain embodiments, the present invention's is equal
Particle (such as containing the particle of the most modified peptide) in one nanoparticle compositions has in about 10 nanometers and about 600 nanometers
In the range of diameter.In certain embodiments, the particle in the homogeneous nanoparticle compositions of the present invention (such as contains without repairing
The particle of the peptide of decorations) have at about 10nm to about 300nm, about 10nm to about 200nm, about 10nm to about 150nm, about 10nm to about
130nm, about 10nm are to about 120nm, about 10nm to about 115nm, about 10nm to about 110nm, about 10nm to about 100nm or about 10nm
Diameter in the range of about 90nm.In certain embodiments, the particle in the meat poisoning nanoparticle compositions of the present invention (such as contains
Have the particle of the most modified peptide) have less than about 300nm, about 250nm, about 200nm, about 150nm, about 130nm, about 120nm,
The mean diameter of about 115nm, about 110nm, about 100nm or about 90nm.In certain embodiments, mean diameter at about 10nm to about
300nm, about 50nm are to about 250nm, about 60nm to about 200nm, about 65nm to about 150nm, about 70nm to the scope of about 130nm
In.In certain embodiments, mean diameter is about 80nm to about 110nm.In certain embodiments, mean diameter is about 90nm and arrives
About 100nm.In certain embodiments, the most of particle in the homogeneous nanoparticle compositions of the present invention (such as contain without
The particle of the peptide modified) there is below specified size or diameter within the specified range.In certain embodiments, described major part
Be greater than in compositions 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,
99.5%, the particle of 99.6%, 99.7%, 99.8%, 99.9% or more than 99.9%.In some embodiments of the invention,
Homogeneous nanoparticle compositions is that the microfluidization by sample realizes.In some embodiments of the invention, homogeneous nanometer
Particle composition is to prepare by being exposed under high shear force (such as passing through microfluidization).
The most modified peptide: as used herein, term " the most modified peptide " refers to not yet pass and aims at peptide
The interpolation of other covalently bonded functional group of transdermal transfer carry out the peptide of chemical modification.In certain embodiments, described peptide is not yet
Position, side acetyl group and/or palmityl is added through chemical modification.In certain embodiments, peptide not yet adds through chemical modification
Any functionality side base.
Embodiment
Nanoparticle
As discussed herein, the present invention provides the combinations of nanoparticles including one or more the most modified peptides
Thing.In certain embodiments, in addition to the most modified described peptide, described nanoparticle compositions farther includes one or one
Other bioactivator above.In certain embodiments, nanoparticle compositions is to adjust by one or more other components
Join, such as, allocate in medicine or Toiletry preparation.In certain embodiments, described medicine or Toiletry preparation are formulated with reality
The transdermal transfer of the most modified peptide (and/or one or more other bioactivators).
In certain embodiments, the nanoparticle compositions of the present invention is stable.In certain embodiments, described nanometer
Particle composition is homogeneous.
In certain embodiments, homogeneous nanoparticle compositions comprises the difference between a group minimum diameter and maximum gauge not
Exceed about 600nm, about 550nm, about 500nm, about 450nm, about 400nm, about 350nm, about 300nm, about 250nm, about 200nm,
The particle of about 150nm or about 100nm.
In certain embodiments, the nanoparticle of the present invention has less than about 1000nm, about 600nm, about 550nm, about
500nm, about 450nm, about 400nm, about 350nm, about 300nm, about 250nm, about 200nm, about 150nm, about 130nm, about
120nm, about 115nm, about 110nm, about 100nm, about 90nm, about 80nm, about 50nm or 50nm diameter below.
In certain embodiments, the nanoparticle of the present invention have 1nm to 1000nm, 1nm to 600nm, 1nm to 500nm,
1nm to 400nm, 1nm to 300nm, 1nm to 200nm, 1nm to 150nm, 1nm to 120nm, 1nm to 100nm, 1nm to 75nm,
The diameter of 1nm to 50nm or 1nm to 25nm.In certain embodiments, the nanoparticle of the present invention has 1nm to 15nm, 15nm
Diameter to 200nm, 25nm to 200nm, 50nm to 200nm or 75nm to 200nm.
In certain embodiments, the distribution of total particle is contained in the particle diameter size range specified.In some embodiments
In, less than 50%, 25%, 10%, 5% or 1% the distribution of total particle beyond the particle diameter size range specified.Real at some
Executing in example, the total particle distribution less than 1% is beyond the particle diameter size range specified.In certain embodiments, nanoparticle
Compositions is substantially free of diameter more than 300nm, 250nm, 200nm, 150nm, 120nm, 100nm, 75nm, 50nm or 25nm
Particle.
In certain embodiments, the nanoparticle in the nanoparticle compositions of the present invention has less than about 300nm, about
250nm, about 200nm, about 150nm, about 130nm, about 120nm, about 115nm, about 110nm, about 100nm, about 90nm or about 50nm
Mean diameter.In certain embodiments, mean diameter at about 10nm to about 300nm, 50nm to about 250nm, 60nm to about
200nm, 65nm are in the range of about 150nm or 70nm to about 130nm.In certain embodiments, mean diameter is about 80nm and arrives
About 110nm.In certain embodiments, mean diameter is about 90nm to about 100nm.
In certain embodiments, the nanoparticle compositions of the present invention is substantially free of the diameter particle more than 300nm.Tool
For body, in certain embodiments, in the nanoparticle compositions of the present invention less than 50% nanoparticle have more than 300nm
Diameter.In certain embodiments, the particle less than 25% has the diameter more than 300nm.In certain embodiments, it is less than
20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%,
3%, the particle of 2%, 1%, 0.5% or less than 0.5% has the diameter more than 300nm.Additionally, in certain embodiments, this
Nanoparticle in the nanoparticle compositions of invention has the diameter in the range of 10nm to 300nm.
In certain embodiments, the nanoparticle compositions of the present invention is substantially free of the diameter particle more than 200nm.Tool
For body, in certain embodiments, in the nanoparticle compositions of the present invention less than 50% nanoparticle have more than 200nm
Diameter.In certain embodiments, the particle less than 25% has the diameter more than 200nm.In certain embodiments, it is less than
20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%,
3%, the particle of 2%, 1%, 0.5% or less than 0.5% has the diameter more than 200nm.Additionally, in certain embodiments, this
Nanoparticle in the nanoparticle compositions of invention has the diameter in the range of 10nm to 200nm.
In certain embodiments, the nanoparticle compositions of the present invention is substantially free of the diameter particle more than 120nm.Tool
For body, in certain embodiments, in the nanoparticle compositions of the present invention less than 50% nanoparticle have more than 120nm
Diameter.In certain embodiments, the particle less than 25% has the diameter more than 120nm.In certain embodiments, it is less than
20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%,
3%, the particle of 2%, 1%, 0.5% or less than 0.5% has the diameter more than 120nm.Additionally, in certain embodiments, this
Nanoparticle in the nanoparticle compositions of invention has the diameter in the range of 10nm to 120nm.
In certain embodiments, the most of nanoparticle in the compositions of the present invention has below specified size or is referring to
Diameter in the range of Ding.In certain embodiments, described major part be greater than in compositions 50%, 60%, 70%, 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or
The particle of more than 99.9%.
Zeta potential is the measuring of electromotive force at shear surface.Shear surface be by with the surface of solids (nanoparticle of the such as present invention
Surface) combine and show a thin layer liquid of elastic behavior and remaining liquid (the such as liquid dispersion showing normal viscous behavior
Medium) the empty surface (imaginary surface) that separates.In certain embodiments, the nanoparticle of the present invention has Jie
Zeta potential in the range of between-50mV to+50mV.In certain embodiments, the nanoparticle of the present invention have between-
Zeta potential in the range of between 25mV to+25mV.In certain embodiments, the nanoparticle of the present invention has between-10mV
Zeta potential in the range of between+10mV.
In certain embodiments, the nanoparticle compositions of the present invention is emulsion or dispersion liquid.In general, emulsion or point
Dissipating liquid to be formed by the immiscible material of at least two, one of which will constitute disperse medium, i.e. particle (such as nanoparticle, its
Constitute " medium being dispersed through ") liquid medium that is dispersed therein." oil-in-water " dispersion liquid is that oily particle is scattered in aqueous and divides
Dispersion liquid in dispersion media." Water-In-Oil " dispersion liquid is the dispersion liquid that aqueous particles is scattered in oiliness disperse medium.Affiliated neck
Territory skill will appreciate that dispersion liquid can be formed by any two unmixability medium and be not strictly limited to aqueous medium with
The combination of oil medium.Therefore, term " disperse medium " is widely used in any disperse medium, although generally mention " aqueous " and
" oiliness " classification.For example, emulsion or dispersion liquid can be by unmixings such as hydrophobicity/hydroaropic substance, polar/non-polar materials
Group prepare, do not consider that described material is " aqueous " or " oiliness " strictly speaking.
In certain embodiments, the nanoparticle compositions of the present invention comprises micellar structure (the most described nanoparticle is
Micelle).In certain embodiments, described micellar structure is cross-linked structure.In certain embodiments, described micellar structure is not for handing over
Connection structure.
In certain embodiments, the nanoparticle compositions of the present invention is by the set self assembly of combination partner.Real at some
Executing in example, the nanoparticle compositions of the present invention is by making component combination (that is, " pre-composition ") stand high shear force and prepare.
In certain embodiments, high shear force is by high pressure, applies by cavitation, by homogenizing and/or by microfluidization.?
In some embodiments, the nanoparticle of combination is formed component agitation, stirs or mix.In embodiment some described,
Described component was made to stand high shear force after mixing.In particular embodiments, mixing can perform a period of time, the least
In 1 hour or more than 5,6,7,8,9,10,11,12,13,14 or 15 hours.In certain embodiments, reach to dissolve.
In some embodiments of the invention, the manufacture of nanoparticle compositions include dialyse component set, such as with
Remove any organic solvent, and/or lyophilization is to produce compositions.
In some embodiments utilizing pre-composition of the present invention, it should be understood that Premix Component can apply high shear force it
Before be assembled into particle.Particle described at least some can be microgranule or even nanoparticle.In certain embodiments, the present invention
Nanoparticle compositions is prepared by pre-composition, and wherein pre-composition is selected from the group comprising suspension or microemulsion.But, at some
In embodiment, applying before high shear force, in pre-composition and be formed without particle structure.
In some embodiments of the invention, the component in the presence of final nanoparticle compositions is whole in pre-composition
Exist and stand high shear force to produce nanoparticle compositions.In some embodiments of the invention, final nanoparticle subgroup
One or more components in the presence of compound do not exist or with less than final nanoparticle compositions in pre-composition
In amount be present in pre-composition.It is to say, in some embodiments of the invention, shearing force is stood making pre-composition
After, in nanoparticle compositions, add one or more materials.
In certain embodiments of the present invention, before applying high shear force, pre-composition is prepared as solution.Especially for
Nanoparticle compositions including at least one bioactivator (the most modified peptide), it is often necessary to first by biological activity
Agent is dissolved in pre-composition, with after-applied shearing force.Therefore, in many examples, bioactivator dissolves at least
A kind of medium (or combination of used medium in pre-composition).In some embodiments of the invention, described dissolving needs heating;?
In other embodiments, it need not heating.
In some embodiments of the invention, nanoparticle compositions is prepared by the component including following: Yi Zhonghuo
More than one aqueouss, polarity or hydrophilic media, one or more oiliness, nonpolar or hydrophobic medium, one or one
Kind of above micellar fractions, one or more surfactants or emulsifying agent, one or more bioactivators and/or
One or more release retardant etc..
Those skilled in the art should fully know and can be used as disperse medium according to the present invention or be intended to scattered medium
Suitable aqueous medium.Representative described aqueous medium includes that (such as) water, normal saline solution (include phosphate-buffered physiology salt
Water), water for injection, short chain alcohol, 5% glucose, Ringer's mixture (Ringer ' s solution) (lactated ringer's injection,
Lactated Ringer'S Solution adds 5% glucose injection, acylated Ringer injection), promise Mosso-M (Normosol-M), Ai Suolite
E (Isolyte E) etc. and a combination thereof.
Those skilled in the art also should fully know and can be used as disperse medium according to the present invention or be intended to scattered medium
Suitable oil medium.In certain embodiments, described oil can comprise one or more fatty acid groups or its salt.One
In a little embodiments, described fatty acid group can comprise digestible, long-chain (such as C8-C50), the hydrocarbon that is substituted or is unsubstituted.
In certain embodiments, described fatty acid group can be C10-C20Fatty acid or its salt.In certain embodiments, fatty acid-based
Group can be C15-C20Fatty acid or its salt.In certain embodiments, fatty acid group can be C15-C25Fatty acid or its salt.
In certain embodiments, fatty acid group can be undersaturated.In certain embodiments, fatty acid group can be single insatiable hunger
Sum.In certain embodiments, fatty acid group can be polyunsaturated.In certain embodiments, unsaturated fatty acids acidic group
The double bond of group can be in cisoid conformation.In certain embodiments, the double bond of unsaturated fatty acids acid groups can be in transoid conformation.
In certain embodiments, fatty acid group can be butanoic acid, caproic acid, octanoic acid, capric acid, lauric acid, myristic acid, palm fibre
One or more in palmitic acid acid, stearic acid, arachidic acid, behenic acid or lignoceric acid.In certain embodiments, fatty acid group
Can be palmitoleic acid, oleic acid, vaccenic acid, linoleic acid, α-linoleic acid, gamma-linoleic acid, arachidonic acid, gadoleic acid, Semen arachidis hypogaeae
One or more in tetraenoic acid, eicosapentaenoic acid, docosahexenoic acid or erucic acid.
In certain embodiments, oil is liquid glycerin three ester.In certain embodiments, oil is middle chain (such as 6-12 carbon)
Triglyceride (such as granny rag traction therapy WL 1349 (Labrafac WL 1349), Oleum Cocois, palm-kernel oil, Lignum cinnamomi camphorae drupe oil etc.).
In certain embodiments, oil is short chain (such as 2-5 carbon) triglyceride.In certain embodiments, oil (is greater than for long-chain
12 carbon) triglyceride (such as soybean oil, Oleum helianthi etc.).
Suitable oil for the present invention includes, but is not limited to almond oil (almond oil), Fructus Pruni nucleolus oil
(apricotkernel oil), American Avocado Tree oil, babassu oil, oleum bergamottae, seed of black currant oil, borage oil, cade oil, Flos Chrysanthemi
Oil, Canola oil, caraway oil, babassu oil, Oleum Ricini, Oleum Cinnamomi, cupu oil, Oleum Cocois, code-liver oil, coffee bean oil., jade
Miyou, Oleum Gossypii semen, fat of Oromaius norvaehollandeae, Eucalyptus oil, Radix Oenotherae erythrosepalae oil, fish oil, Semen Lini oil, geraniol oil, calaba oil, Oleum Vitis viniferae, hazel
Fruit oil, oil of hyssop, isopropyl myristate, jojoba, Hawaii kernel oil (kukui nut oil), lavandin oil, Garden lavender
Oil, Fructus Citri Limoniae oil, litsea cubeba oil (litsea cubeba oil), macadimia nut oil (macademianut oil), Radix Malvae sylvestris oil, awns
Really seed awns flower seed oil oily, white, mineral oil, ermine oil, Semen Myristicae oil (nutmeg oil), olive oil, oleum Citri sinensis, bathypelagic fish oil
(orange roughy oil), Petiolus Trachycarpi oil, palm-kernel oil, peach kernel oil, Oleum Arachidis hypogaeae semen, poppy seed oil, Semen Cucurbitae oil, rapeseed oil, rice
Rice oil, oil of rosemary, safflower oil, Oleum Santali albi, Flos Camelliae Japonicae caul-fat (sasquanaoil), savory oil, Oleum Hippophae, Oleum sesami, breast wood
Fruit oil, silicone oil, soybean oil, Oleum helianthi, tea tree oil, Ji oil, Flos Camelliae Japonicae oil (tsubaki oil), vetiver oil, Oleum Juglandis, little
Wheat germ oil and its mixture.Suitable artificial oil for the present invention includes, but is not limited to: caprylic/capric triglyceride,
Cyclomethicone (cyclomethicone), ethyl sebacate, simethicone 360 (dimethicone 360), meat
Isopropyl myristate, octyldodecanol, oleyl alcohol and a combination thereof.
Suitable micellar fractions can include (such as) one or more amphiphilic entities.The amphiphilic entity being suitable for includes sky
So entity, synthesis entity and containing natural and synthesis component entity.In certain embodiments, amphiphilic entity can comprise one or
More than one polymer and/or one or more there is the compound of polymerization property.
In general, amphiphilic entity is to have hydrophobicity and hydrophilic entity simultaneously.Such as those skilled in the art
It will be appreciated that amphiphilic entity can be included in many different ways.In certain embodiments, amphiphilic entity can comprise one or
More than kind, self has amphipathic individual compound or molecule.Only giving a few examples, described compound or molecule include Polyethylene Glycol
(PEG), phospholipid, cholesterol, glycolipid fatty acid, bile acid and saponin.According to FDA Food and Drug Administration (USFood and
Drug Administration), it is generally recognized that PEG is safe for food, cosmetics and medicine.PEG water soluble, nothing
Poison, odorless, lubrication, non-volatile and nonirritant.
In certain embodiments, amphiphilic entity can comprise one or more and self not have amphipathic but have certain
Hydrophilic or the individual components of hydrophobic property.In the described embodiment, two or more described non-amphiphilic component is generally by phase
Associating mutually makes the assembling thing of individual components have amphipathic.Described association potentially includes or may not include covalent bond;Institute
State association and can include that non-covalently bonded is (such as by electrostatic interaction, affinity interaction, hydrophobic interaction, hydrogen
Bond, Van der Waals (Van der Waals) interaction, ionic interaction, dipole-dipole interaction etc.).General next
Saying, described association can include any forces associated, key or sticking method.
In certain embodiments, amphiphilic entity used according to the invention can be had different hydrophilic by two or more
Property or hydrophobicity degree individual components constitute.In certain embodiments, amphiphilic entity can comprise at least one hydrophilic component
With at least one hydrophobic components.In certain embodiments, " hydrophilic " and " hydrophobicity " component is relative to each other hydrophilic
Or hydrophobicity.
In certain embodiments, the component of two or more different hydrophilic or hydrophobicity degree can pass through covalent bond
And bond is together to form homopolymer or copolymer.In certain embodiments, copolymer can be block copolymer.At some
In embodiment, copolymer can be graft copolymer.
In certain embodiments, amphiphilic entity can comprise amphiphilic block copolymer or is made up of amphiphilic block copolymer.?
In some embodiments, amphiphilic block copolymer can be diblock copolymer.In certain embodiments, amphiphilic diblock copolymer
Can be included in the first covalently bound polymer blocks of the end of the chain and the second polymer blocks.In a particular embodiment, the first polymerization
Thing block can comprise the repetitive of hydrophilic component, and the second polymer blocks can comprise the repetitive of hydrophobic components.
In a particular embodiment, the first polymer blocks can comprise the repetitive of hydrophobic components, and the second polymer blocks can wrap
Repetitive containing hydrophilic component.In certain embodiments, amphiphilic block copolymer can be segmented copolymer.At some
In embodiment, amphiphilic block copolymer can be included in the multiple the most embedding of two or more covalently bound polymer of the end of the chain
Section.In a particular embodiment, amphiphilic block copolymer can be included in the covalently bound multiple hydrophilic block alternately of the end of the chain and
Hydrophobic block.In a particular embodiment, each block of alternating block can comprise the weight of hydrophilic component or hydrophobic components
Multiple unit.
In certain embodiments, amphiphilic entity can comprise amphipathic graft copolymer or is made up of amphipathic graft copolymer.?
In some embodiments, amphipathic graft copolymer can comprise the side chain being covalently attached to other polymer blocks polymer blocks or
It is made up of the polymer blocks of the side chain being covalently attached to other polymer blocks.In a particular embodiment, each polymer is embedding
Section can comprise hydrophilic component or the repetitive of hydrophobic components or by hydrophilic component or the repetitive of hydrophobic components
Composition.In certain embodiments, amphipathic graft copolymer can comprise the first polymer blocks and be covalently attached to the first polymer
Second polymer blocks of the side chain of block, or by the first polymer blocks and the side chain being covalently attached to the first polymer blocks
Second polymer blocks composition.In certain embodiments, the first polymer blocks can comprise the repetitive of hydrophilic component
Or be made up of the repetitive of hydrophilic component, and the second block can comprise the repetitive of hydrophobic components.Implement at some
In example, the first polymer blocks can comprise the repetitive of hydrophobic components or is made up of the repetitive of hydrophobic components, and
Second polymer blocks can comprise the repetitive of hydrophilic component.
In certain embodiments, amphiphilic block or graft copolymer can include that the hydrophilic of the repetitive comprising polysaccharide gathers
Compound block and comprise the hydrophobic polymer block of repetitive of polyester or polysaccharide.Alternatively or additionally, amphiphilic block or
Graft copolymer can include the hydrophobic polymer block of the repetitive comprising polysaccharide and comprise the repetition list of polyester or polysaccharide
The hydrophilic polymer blocks of unit.Described hydrophilic polymer blocks can be containing the repetition list of any kind of hydrophilic polymer
Unit, such as polysaccharide (such as amylopectin (pullulan)) or polyoxygenated alkene (such as polyethylene glycol oxide).Hydrophobic polymer
Block can be containing the repetitive of any kind of hydrophobic polymer, such as polycaprolactone or polyamide (such as polycaprolactam
Amine).
In certain embodiments, the hydrophilic parts of amphiphilic entity can be nonionic.In certain embodiments, amphiphilic
The hydrophilic component of entity comprises one or more ionic groups.In general, described ionic group be hydrophilic and
Hydrophilic nmature can be given to amphiphilic entity.
In certain embodiments, ionic group can be cation.In certain embodiments, cation group can be ammonium
Ion (NH4 +), nitre ion (NO2 +), Nitrosonium ion (NO+), hydrogen ion (H3O+), mercurous ion (Hg2 2+), phosphorus
Ion (PH4 +), vanadyl ion (VO2+) or its salt.
In certain embodiments, ionic group can be anion.In certain embodiments, anionic group can be fat
Fat acid group, arsenic ion (As3-), azide ion (N3 -), bromide ion (Br-), chloride ion (Cl-), fluorion (F-), hydrion (H-), iodine
Ion (I-), Nitrogen ion (N3-), oxonium ion (O2-), phosphonium ion (P3-), plasma selenium (Se2-), sulphion (S2-), peroxide
(O2 2-), arsenate (AsO4 3-), arsenous anion (AsO3 3-), borate (BO3 3-), hyperbromic acid root (BrO4 -), bromate
(Bro3 -), bromous acid root (BrO2 -), Hydrogen oxybromide (HOBr) root (BrO-), carbonate (CO3 2-), bicarbonate radical (HCO3 -), chlorate anions
(ClO3 -), perchlorate (ClO4 -), chlorite (ClO2 -), hypochlorite (ClO-), chromate (CrO4 2-), dichromate ion
(Cr2O7 2-), high fluoric acid root (BrO4 -), fluoric acid root (BrO3 -), sub-fluoric acid root (BrO2 -), Fluorine monohydroxide root (BrO-), periodate
(IO4 -), iodate (IO3 -), idous acid group (IO2 -), Hypoiodous acid (HIO) root (IO-), nitrate anion (NO3 -), nitrite anions (NO2 -), phosphoric acid
Root (PO4 3-), hydrogen phosphate (HPO4 2-), dihydrogen phosphate (H2PO4 -), orthophosphite (PO3 3-), silicate (SiO3 2-), sulphuric acid
Root (SO4 2-), thiosulfate anion (S2O3 2-), bisulfate ion (HSO4 -), inferior sulfate radical (SO3 2-), bisulfite (HSO3 -), sulphur
Acid group (-S (=O)2-O-), acetate (C2H3O2 -), formate (HCO2 -), oxalate (C2O4 2-), oxalic acid hydrogen radical (HC2O4 -), lemon
Lemon acid group (C6H5O7 3-), amber acid radical (C4H4O4 2-), fumaric acid radical (C4H2O4 2-), malate (C4H5O5 2-), sulfur hydrogen radical
(HS-), tellurium ion (Te2-), amide (NH2 -), cyanate radical (OCN-), thiocyanate radical (SCN-), cyanogen root (CN-), hydroxyl
(OH-), MnO4 (MnO4 -) or its salt.
In certain embodiments, the hydrophilic component of amphiphilic entity can comprise nucleic acid or is made up of nucleic acid.For example, core
Acid polymer can include DNA, RNA or a combination thereof.In certain embodiments, nucleic acid polymers can be oligonucleotide and/or many
Nucleotide.In certain embodiments, nucleic acid polymers can be oligonucleotide and/or modified oligonucleotide;Antisense widow's core
Thuja acid and/or modified antisense oligonucleotide;cDNA;Genomic DNA;Viral DNA and/or RNA;DNA and/or prna chimera
Body;Plasmid;Cosmid;Genetic fragment;Artificial and/or native chromosomal (such as yeast artificial chromosome) and/or one part;
RNA (such as mRNA, tRNA, rRNA and/or ribozyme);Peptide nucleic acid(PNA) (PNA);Comprise the polynucleotide of the synthetic analogues of nucleic acid,
It can be modified or the most modified;The DNA of various versions, including single stranded DNA, double-stranded DNA, super coiled DNA and/or three spiral shells
Rotation DNA;Z-DNA;And/or a combination thereof.
In certain embodiments, the hydrophilic component of amphiphilic entity can comprise carbohydrate or by carbohydrate group
Become.In certain embodiments, carbohydrate can be in art known by the monosaccharide connected by glycosidic bond (or its
Derivant) polysaccharide that forms.This sugar can include, but is not limited to glucose, fructose, galactose, ribose, lactose, sucrose, wheat
Bud sugar, trehalose, cellobiose, mannose, xylose, arabinose, glucuronic acid, galacturonic acid, mannuronic acid, Fructus Vitis viniferae
Osamine, galactosamine and neuraminic acid.In certain embodiments, polymer can be hydrophilic carbohydrate, including amination,
Carboxylation and sulfated polysaccharides.In certain embodiments, hydrophilic carbohydrate can be following one or more: side chain
Starch, cellulose, microcrystalline Cellulose, hydroxypropyl methyl cellulose, hydroxylated cellulose, methylcellulose, glucosan, ring Portugal gather
Sugar, glycogen, starch, hetastarch, carrageenin, glycosyl (glycon), amylose (amylose), chitosan, N, O-carboxylic
Methyl chitosan, alginate jelly and alginic acid, starch, chitin, heparin, Rhizoma amorphophalli (konjac), glucomannoglycan, pustulan, heparin,
Hyaluronic acid, curdlan (curdlan) and xanthan gum (xanthan).In certain embodiments, hy-drophilic polysaccharide can be by drawing
Enter many pendant hydrophobic bases to be modified to become hydrophobicity.In certain embodiments, hydrophobic carbohydrate can include
Cellulose acetate, amylopectin acetas, Rhizoma amorphophalli acetas, amylose acetate and glucosan acetas.
In certain embodiments, the hydrophilic component of amphiphilic entity can comprise natural gum or is made up of natural gum, described natural gum bag
Include (but not limited to) xanthan gum, alginic acid, POLY-karaya, sodium alginate and/or locust bean gum.
In certain embodiments, a kind of component of amphiphilic entity can comprise protein or is made up of protein.Real at some
Executing in example, protein is the hydrophilic component of amphiphilic entity.In other embodiments, protein is the hydrophobicity group of amphiphilic entity
Point.Albumin, collagen protein or poly-(aminoacid) (example is included, but is not limited to according to the spendable exemplary proteins of the present invention
Such as polylysine).
In certain embodiments, the hydrophobic components of amphiphilic entity can comprise one or more fatty acid groups or its
Salt or be made up of one or more fatty acid groups or its salt.In general, described group is generally of hydrophobicity and can
To amphiphilic entity hydrophobic property matter.In certain embodiments, fatty acid group can comprise digestible, long-chain (such as C8-
C50), the hydrocarbon that is substituted or is unsubstituted.In certain embodiments, fatty acid group can be C10-C20Fatty acid or its salt.?
In some embodiments, fatty acid group can be C15-C20Fatty acid or its salt.In certain embodiments, fatty acid group is permissible
It is C15-C25Fatty acid or its salt.In certain embodiments, fatty acid group can be undersaturated.In certain embodiments,
Fatty acid group can be monounsaturated.In certain embodiments, fatty acid group can be polyunsaturated.Real at some
Executing in example, the double bond of unsaturated fatty acids acid groups can be in cisoid conformation.In certain embodiments, the double bond of unsaturated fatty acid can
In transoid conformation.
In certain embodiments, fatty acid group can be butanoic acid, caproic acid, octanoic acid, capric acid, lauric acid, myristic acid, palm fibre
One or more in palmitic acid acid, stearic acid, arachidic acid, behenic acid or lignoceric acid.In certain embodiments, fatty acid group
Can be palmitoleic acid, oleic acid, vaccenic acid, linoleic acid, α-linoleic acid, gamma-linoleic acid, arachidonic acid, gadoleic acid, Semen arachidis hypogaeae four
One or more in olefin(e) acid, eicosapentaenoic acid, docosahexenoic acid or erucic acid.
In certain embodiments, the hydrophobic components of amphiphilic entity can comprise one or more biocompatibility and/
Or biodegradable synthetic polymer, or gathered by one or more biocompatibility and/or biodegradable synthesis
Compound forms, and described synthetic polymer includes (such as) Merlon (the most poly-(1,3-dioxane-2 ketone)), polyacids
Acid anhydride (the most poly-(sebacic anhydride)), polyhydroxy acid (the most poly-(beta-hydroxy alkanoic acid ester)), poly-propyl fumarate, polycaprolactone, poly-
Amide (such as polycaprolactam), polyacetals, polyethers, polyester (such as polylactide and PGA), biodegradable poly-
Cyanoacrylate, polyvinyl alcohol and biodegradable polyurethane.For example, amphiphilic entity can comprise following one or
Kind of above biodegradable polymer: poly-(lactic acid), poly-(glycolic), poly-(caprolactone), PLG,
Poly-(lactide-co-caprolactone), poly-(Acetic acid, hydroxy-, bimol. cyclic ester-co-caprolactone) and poly-(DL-lactide-co-glycolide).
In certain embodiments, the hydrophobic components of amphiphilic entity can comprise one or more acrylic acid series polymeric compounds
Or be made up of one or more acrylic acid series polymeric compounds.In certain embodiments, acrylic acid series polymeric compounds includes (such as)
Acrylic acid and methacrylic acid copolymer, methylmethacrylate copolymer, ethoxyethyl methacrylates, methacrylic acid
Cyanaoethyl methacrylate, methacrylic acid amino alkyl ester copolymer, poly-(acrylic acid), poly-(methacrylic acid), methacrylate acyl
Amine copolymer thing, poly-(methyl methacrylate), poly-(methacrylic anhydride), methyl methacrylate, polymethacrylates, poly-
(methyl methacrylate) copolymer, polyacrylamide, methacrylic acid amino alkyl ester copolymer, methyl propenoic acid glycidyl
Ester copolymer and the combination comprising one or more above-mentioned polymer.Described acrylic acid series polymeric compounds can comprise and has low containing
The acrylate of the quaternary ammonium group of amount and the full polymerized copolymers of methacrylate.
In certain embodiments, the hydrophobic components of amphiphilic entity can comprise polyester or is made up of polyester.Exemplary described
Polyester include (such as) poly alkylene glycol, PLGA, Pegylation poly-(lactic-co-glycolic acid),
Poly-(lactic acid), Pegylation poly-(lactic acid), poly-(glycolic), Pegylation poly-(glycolic), polylactic acid and polyglycolic acid
Copolymer and its derivant.In certain embodiments, polyester includes (such as) condensing model, poly-(ortho esters), Pegylation
Poly-(ortho esters), poly-(caprolactone), Pegylation poly-(caprolactone), polylysine, Pegylation polylysine, poly-(Asia
Ethylimido), Pegylation poly-(ethylenimine) and its derivant.In certain embodiments, polyester can include (such as)
Polycaprolactone, poly-(L-lactide-co-1B), poly-(serine ester), poly-(CHP ester), poly-[α-(4-
Aminobutyl)-L-glycolic] and its derivant.
Suitably surfactant or emulsifying agent includes, but is not limited to: phosphoglyceride;Phosphatidylcholine;Two palmityls
Base phosphatidylcholine (DPPC);DOPE (DOPE);Dioleoyl epoxide propyl group three second ammonium (DOTMA);Two oil
Phosphatidyl choline;Cholesterol;Cholesteryl ester;DG;DG succinate;Diphosphatidylglycerol
(DPPG);Hexadecanol;The fatty alcohol such as such as Polyethylene Glycol (PEG);Polyoxyethylene-9-Laurel ether;Such as Palmic acid or oleic acid
Deng surface active fatty acid;Fatty acid;Fatty acid amide;Sorbitan trioleate (Si Pan (Span) 85) glycocholic acid
Salt;Sorbitan monolaurate (this Pan 20);TWEEN-20 (tween (Tween)-20);Polysorbate 60
(Tween-60);Polysorbate 65 (Tween-65);Polysorbate 80 (tween 80);Polysorbate 85 (tween 85);
Polyoxyethylene monostearate;Surfactin (surfactin);Poloxamer (poloxomer);Such as sorbitan
The sorbitan fatty acid esters such as trioleate;Lecithin;LYSOLECITHIN SUNLECITHIN A;Phosphatidylserine;Phosphatidylinositols;Sheath phosphorus
Fat;PHOSPHATIDYL ETHANOLAMINE (cephalin);Cuorin;Phosphatidic acid;Cerebroside;DCP;DPPG;
Stearylamine;Dodecyl amine;Cetylamine;Acetyl palmitate;Glycerol ricinoleate;Cetyl stearic;Tai Luosha
Pool (tyloxapol);PEG 5000-PHOSPHATIDYL ETHANOLAMINE;PEG 400-monostearate;And phospholipid.Institute
State the mixture that surface active agent composition can be different surfaces activating agent.These surfactants can from natural origin extract and
Purification or can prepare with synthesis mode in the lab.In a preferred embodiment, surfactant can be from buying on the market.
In certain embodiments of the present invention, select and adjust the component of nanoparticle compositions for preparing the present invention
Relative quantity to produce, there is the nanoparticle of required feature.In certain embodiments, oil and surfactant be with between
Ratio in the range of between 0.25-10 uses.In certain embodiments, oil and the ratio of surfactant are about 0.25:
1, about 0.5: 1, about 1: 1, about 2: 1, about 3: 1, about 4: 1, about 5: 1, about 6: 1, about 7: 1, about 8: 1, about 9: 1 or about 10: 1.One
In a little embodiments, the ratio of surfactant and oil is about 0.5: 1, about 1: 1, about 2: 1, about 3: 1, about 4: 1, about 5: 1, about 6: 1,
About 7: 1, about 8: 1, about 9: 1 or about 10: 1.In certain embodiments, oil and surfactant are with between 0.25-2
In the range of ratio use.In certain embodiments, oil and the ratio of surfactant be about 0.25: 1, about 0.5: 1, about 1:
1 or about 2: 1.In certain embodiments, surfactant is about 0.5: 1, about 1: 1 or about 2: 1 with the ratio of oil.Implement at some
In example, oil is about 1: 1 with the ratio of surfactant.
In certain embodiments, it is used for preparing the percent of (such as in pre-composition) oil in the compositions of nanoparticle be situated between
In the range of between 0% to 30%.In certain embodiments, it is used for preparing (such as pre-composition in the compositions of nanoparticle
In) percent of oil is about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 9%, about 10%, about 11%,
About 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%,
About 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29% or about 30%.In certain embodiments, oil
Percent is about 8%.In certain embodiments, the percent of oil is about 5%.
In certain embodiments, when using one or more amphiphilic entities, it is used for preparing the combination of nanoparticle
In thing, (such as in pre-composition), the percent of amphiphilic entity can arrive 40% to 99%, 50% to 99%, 60% to 99%, 70%
99%, in the range of 80% to 99%, 80% to 90% or 90% to 99%.In certain embodiments, it is used for preparing nanoparticle
In the compositions of son the percent of (such as in pre-composition) amphiphilic entity be about 75%, about 76%, about 77%, about 78%, about
79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about
90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or about 99%.
The percent of the material in pre-composition with surfactant activity can be 0% to 99%, 10% to 99%, 25%
In the range of 99%, 50% to 99% or 75% to 99%.In certain embodiments, pre-composition has surfactant live
The percent of the material of property can be in the range of 0% to 75%, 0% to 50%, 0% to 25% or 0% to 10%.Real at some
Execute in example, be used for preparing in the compositions of nanoparticle the percent of (such as in pre-composition) surfactant between 0%-
In the range of between 30%.In certain embodiments, the percent of surfactant be about 1%, about 2%, about 3%, about 4%,
About 5%, about 6%, about 7%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about
17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about
28%, about 29% or about 30%.In certain embodiments, the percent of surfactant is about 8%.In certain embodiments,
The percent of surfactant is about 5%.
In certain embodiments, nanoparticle compositions does not contains more than one oil.In certain embodiments, nanoparticle
Compositions can comprise two or more oil.In certain embodiments, nanoparticle compositions does not contains more than one surface
Activating agent.In certain embodiments, nanoparticle compositions can comprise two or more surfactant.Implement at some
In example, nanoparticle compositions is entirely free of poisonous component or is substantially free of poisonous component.
In certain embodiments, nanoparticle compositions is substantially lived by water, oil, surfactant and at least one biology
Property agent (the most modified peptide) composition.In certain embodiments, nanoparticle compositions is substantially lived by water, oil, surface
Property agent, at least one bioactivator and at least one for produce and/or preserve nanoparticle compositions material composition.
In certain embodiments, nanoparticle compositions is made up of water, oil, surfactant and the most modified peptide.?
In some embodiments, nanoparticle compositions by water, oil, surfactant, the most modified peptide and at least one be used for producing
And/or preserve the material composition of nanoparticle.
The most modified peptide
Any one in various peptides all may be incorporated into according in the nanoparticle compositions of the present invention.In most of embodiments
In, the length of peptide is less than about 100 aminoacid;In certain embodiments, the length of peptide be less than about 90, about 80, about 70,
About 65, about 60, about 55, about 50, about 45, about 40, about 35, about 30, about 25, about 20, about 15,
About 13, about 12, about 10, about 9, about 8, about 7, about 6 or about 5 aminoacid.In particular embodiments,
Described peptide is pentapeptide.In certain embodiments, the peptide in nanoparticle compositions to be incorporated to only comprises naturally occurring aminoacid.
In certain embodiments, peptide comprises the aminoacid of one or more non-naturally-occurrings.
The most modified small peptide used according to the invention is typically at skin (including epidermis and corium), subcutaneous tissue
There is in (including fatty tissue) and/or proximal muscles bioactive peptide.Described peptide includes, but is not limited to: promote extracellular
Peptide (such as, KTTKS, the SEQ ID NO.:1 that substrate produces;EYKTTKSSRL, SEQ ID NO.:2;VIEYKTTK, SEQ ID
NO.:3;KTTK, SEQ ID NO.:4;GKTVIEYKTTKS, SEQ ID NO.:5;GKTVIEYKTTKSSRL, SEQ ID NO.:
6;WGKTVIEYKTTKSSRLPIID, SEQ ID NO.:7;CTSHTGAWGKTVIEYKTTKS, SEQ ID NO.:8;TTKS,
SEQ ID NO.:9), the peptide (such as, EEMQRR, SEQ ID NO.:10) of wrinkle can be reduced, improve the peptide (example of wound healing
As, gastrin releasing peptide, VGVAPG, SEQ ID NO.:11;YYRADA, SEQ ID NO.:12;GHK, SEQ ID NO.:13,
Interferon, interferon inducers) and treatment cause such as hypertrophic cicatrix, keloid and limitation or systemic sclerosis (hard
Skin is sick) etc. peptide (such as, the P144 of extracellular matrix excess accumulation of condition of illness;TSLDASIIWAMMQN, SEQ IDNO.:14) (sheet
Mountain (Katayama) et al., see on;Road ripple (Lupo), see on;Robinson (Robinson) et al., see on;Sabeer Bhatia
(Bhartiya) et al., 1992, cytophysiology magazine (J.Cell.Physiol), 150:312;And Santiago
(Santiago) et al., 2005, experimental dermatology magazine (J.Investigative Dermatology), 125:450;Entirely
Portion is incorporated herein by reference).Definition about peptide abbreviation sees table 1 below.
Table 1: peptide is abridged
Popular nameaSymbolbFormal name used at schoolcChemical formula
Alanine Ala A 2-alanine CH3-CH(NH2)-COOH
Arginine Arg R 2-amino-5-guanidinopentanoic acid H2N-C (=NH)-NH-[CH2]3-CH(NH2)-
COOH
Agedoite Asnd Nd2-amino-3-carbamyl propanoic acid H2N-CO-CH2-CH(NH2)-COOH
Aspartic acid Aspd Dd2-aminosuccinic acid HOOC-CH2-CH(NH2)-COOH
Cysteine Cys C 2-amino-3-mercaptopropionic acid HS-CH2-CH(NH2)-COOH
Glutamine Glnd Qd2-amino-4-carbamyl butanoic acid H2N-CO-[CH2]2-CH(NH2)-COOH
Glutamic acid Glud Ed2 aminopentanedioic acid HOOC-[CH2]2-CH(NH2)-COOH
Glycine Gly G glycine CH2(NH2)-COOH
Histidine H 2-amino-3-(1H-imidazol-4 yl)-propanoic acid
Isoleucine Ile I 2-amino-3 methylvaleric acide C2H5-CH(CH3)-CH(NH2)-COOH
Leucine Leu L 2-amino-4-methylvaleric acid (CH3)2CH-CH2-CH(NH2)-COOH
Lysine Lys K 2,6-diaminocaproic acid H2N-[CH2]4-CH(NH2)-COOH
Methionine Met M 2-amino-4-(methyl mercapto) butanoic acid CH3-S-[CH2]2-CH(NH2)-COOH
Phenylalanine Phe F 2-amino-3-phenylpropionic acid C6H5-CH2-CH(NH2)-COOH
Proline Pro P pyrrolidine-2-formic acid
Serine Ser S L-Serine HO-CH2-CH(NH2)-COOH
Threonine Thr T 2 amino 3 hydroxybutyric acid CH3-CH(OH)-CH(NH2)-COOH
Tryptophan Trp W 2-amino-3-(1H-indol-3-yl)-propanoic acid
Tyrosine Tyr Y 2-amino-3-(4-hydroxy phenyl)-propanoic acid
Valine Val V 2-amino-3 Methylbutanoic acid (CH3)2CH-CH(NH2)-COOH
Other component
Showing as referred to herein, the nanoparticle compositions of the present invention can be containing one or more other components or with one
Plant or the combination of more than one other components.Some exemplary other component described is discussed in this article.
Bioactivator
Treat include (such as), diagnose, prevent, nutrition, any biological including cosmetic and/or bentoquatam agent are lived
Property agent all can be transmitted according to the present invention.Described bioactivator can be little molecule, organo-metallic compound, nucleic acid, protein
(including polyprotein, protein complex etc.), peptide, lipid, carbohydrate, medical herbs, hormone, metal, radioelement
With compound, medicine, vaccine, immuning agent etc. and/or a combination thereof.Described biological agent can be encapsulated in the nanoparticle of the present invention
In, on the surface of the nanoparticle being adsorbed in the present invention, it is present in the interface of the nanoparticle of the present invention and/or is present in this
In the micelle film of the nanoparticle of invention.
In certain embodiments, in the compositions of the nanoparticle of preparing the present invention (such as in pre-composition) and/or
The percent of the bioactivator in nanoparticle is in the range of 0.1%-25%.In certain embodiments, bioactivator
Percent in the range of 0.1%-20%, 0.1%-15%, 0.1%-10%, 0.1%-5% or 0.1%-1%.One
In a little embodiments, the percent of bioactivator is at 1%-20%, 5%-20%, 10%-20%, 15%-20% or 15%-
In the range of 25%.In certain embodiments, the percent of bioactivator is less than 0.1%.In certain embodiments, biological alive
Property agent percent more than 25%.In certain embodiments, the percent of bioactivator be about 0.1%, about 0.5%, about
1%, about 2%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about
14%, about 15%, about 16%, about 17%, about 18%, about 18%, about 20%, about 20%, about 1%, about 2%, about 4%, about
5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%,
About 17%, about 18%, about 18%, about 20%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25% or 25% with
On.
Related biological agent can produce according to any available method or approach or obtain.Bioactivator can contain
Or it is modified to be intended to promote the part that it is used in combination with the nanoparticle of the present invention or transmits containing one or more.
Described modification would not disturb the biological activity of medicament.In certain embodiments, modification is the most in vivo removed.Lift
For example, bioactivator can the detectable labelling of labelling and/or can provide in " precursor " form, described " precursor " form is passing
Convert after passing or be modified to activity form.
In certain embodiments, bioactivator is little molecule and/or the organic compound with medicinal activity.At some
In embodiment, described bioactivator is Clinical practice medicine.In certain embodiments, described medicine is antibiotic, antiviral
Agent, anesthetis, anticoagulant, anticarcinogen, enzyme inhibitor, steroid medicament, antiinflammatory, antitumor agent, antigen, vaccine, antibody, solution
Congested agent, hypotensive agent, tranquilizer, birth control agent, progestational agents, cholilytic drug, analgesic, antidepressants, psychosis, β-
Adrenergic blocker, diuretic, cardiac vascular activity agent, vasoactive agent, non-steroid anti-inflammatory agent etc..It is suitable for administered transdermal
Bioactivator be concerned by people especially.
The bioactivator transmitted can be the mixture of pharmaceutical active.For example, local anesthetic can be with all
Such as antiinflammatory combination transmission such as steroid.Local anesthetic also can together with the vasoactive agents such as such as epinephrine administration.Again
As one example, antibiotic can with generally by antibacterial produce the enzyme making described antibiotic inactivate inhibitor (such as penicillin and gram
Clavulanic acid (clavulanic acid)) combination.
In certain embodiments, bioactivator is diagnostic agent.In certain embodiments, diagnostic agent includes gas;For
Positron emission tomography (positron emissions tomography, PET), computer-assisted tomography
(computer assisted tomography, CAT), single photon emission tomography, x-ray, fluoroscopy
Commercial contrast agents with nuclear magnetic resonance (magnetic resonance imaging, MRI);And contrast medium.It is suitable as MRI
In the example of material of contrast medium include gadolinium chelate compound and ferrum, magnesium, manganese, copper and chromium.It is applicable to CAT and x-ray imaging
The example of material includes the material based on iodine.
In certain embodiments, bioactivator is preventive.In certain embodiments, preventive includes vaccine.Vaccine
Can comprise separated protein or peptide, the organism of inactivation and virus, dead organism and virus, the organism of genetic modification or
Virus, and cell extract.Preventive can be be situated between white element, interferon, cytohormone and such as cholera toxin, Alumen, Freund assistant
The adjuvant combinations such as agent (Freund ' s adjuvant).Preventive can include the antigen of the most such as the following bacterial organisms: pneumonia chain
Coccus (Streptococccus pnuemoniae), hemophilus influenza (Haemophilus influenzae), golden yellow Portugal
Grape coccus (Staphylococcus aureus), micrococcus scarlatinae (Streptococcus pyrogenes), Corynebacterium diphtheriae
Bacillus (Corynebacterium diphtheriae), Listeria monoeytogenes
(Listeriamonocytogenes), Bacillus anthracis (Bacillus anthracis), clostridium tetani
(Clostridium tetani), bacillus botulinus (Clostridium botulinum), bacillus perfringens (Clostridium
Perfringens), meningococcus (Neisseria meningitidis), gonococcus (Neisseria
Gonorrhoeae), Streptococcus mutans (Streptococcusmutans), Pseudomonas aeruginosa (Pseudomonas
Aeruginosa), salmonella typhi (Salmonella typhi), haemophilus parainfluenzae (Haemophilus
Parainfluenzae), Bordetella pertussis (Bordetella pertussis), Francisella tularensis
(Francisella tularensis), Yersinia pestis (Yersinia pestis), vibrio cholera (Vibrio
Cholerae), addicted to lung Legionnella (Legionella pneumophila), mycobacterium tuberculosis (Mycobacterium
Tuberculosis), Mycobacterium leprae (Mycobacterium leprae), treponema pallidum (Treponema
Pallidum), leptospira interrogans (Leptospirosis interrogans), Borrelia burgdoyferi (Borrelia
Burgdorferi), campylobacter jejuni (Camphylobacter jejuni) etc.;The antigen of the most such as the following virus: variola,
A type and Type B influenza, respiratory tract merge virus, parainfluenza, measles, HIV, varicella zoster virus, 1 type and the simple bleb of 2 types
Rash, cytomegalovirus, epstein-Barr virus (Epstein-Barr virus), rotavirus, rhinovirus, adenopathy
Poison, papillomavirus, poliovirus, parotitis, rabies, rubella, Coxsackie virus (coxsackievirus),
Equine encephalitis, Japanese encephalitis (Japanese encephalitis), yellow fever, Rift Valley fever (Rift Valley fever), A type, B
Type, c-type, D type and E Hepatitis virus etc.;The most such as the following fungus, the primary and antigen of parasite: Cryptococcus histolyticus
(Cryptococcus neoformans), Histoplasma capsulatum (Histoplasma capsulatum), Candida albicans
(Candida albicans), candida tropicalis (Candidatropicalis), nocardia asteroides (Nocardia
Asteroides), rickettsia rickettsii (Rickettsia ricketsii), rickettsia typhi (Rickettsia
Typhi), mycoplasma pneumoniae (Mycoplasma pneumoniae), chlamydia psittaci (Chlamydial psittaci), sand
Chlamydia oculogenitale (Chlamydial trachomatis), Plasmodium falciparum (Plasmodium falciparum), trypanosoma bocagei
(Trypanosoma brucei), entamoeba historlytica (Entamoebahistolytica), Toxoplasma gondii (Toxoplasma
Gondii), trichomonal vaginitis (Trichomonas vaginalis), Schistosoma mansoni (Schistosoma mansoni) etc.
Deng.These antigens can be in the form of the organism killed completely, peptide, protein, glycoprotein, carbohydrate or a combination thereof.
In certain embodiments, bioactivator can be protein.As used herein, term " protein " and
" peptide " is used interchangeably.In certain embodiments, the size of peptide arrives at about 5 to about 40, about 10 to about 35, about 15
In about 30 or about 20 Dao about 25 amino acid whose scopes.Can use from the peptides organizing peptides more, the peptide in these groups comprise with
Machine sequence and/or sequence the most unanimously change and provide maximum diversified one group of peptide.
In certain embodiments, bioactivator can be antibody.In certain embodiments, antibody can include (but not limiting
In) polyclonal antibody, monoclonal antibody, chimeric (i.e. " humanization ") antibody, strand (restructuring) antibody.In certain embodiments,
Antibody can have effector function and/or the bispecific molecule of minimizing.In certain embodiments, antibody can include Fab fragment and/
Or by fragment produced by Fab expression library.
In certain embodiments, bioactivator can be nucleic acid.In certain embodiments, oligonucleotide comprise DNA,
RNA, chimeric mixtures, derivant, characteristic and/or its modified form.The oligonucleotide of the present invention can be strand and/
Or double-strand.Oligonucleotide can such as be modified at base portion, sugar moieties and/or phosphate backbone, steady to improve molecule
Qualitative, hybridization etc..
In a particular embodiment, nucleic acid comprises and is bound to translation initiation site, transcriptional start site and/or splice site
Antisense molecule.Antisense oligonucleotide will be bound to said target mrna and/or stop translation.Alternatively or additionally, antisense oligonucleotide can
It is bound to the DNA (such as controlling element) of target gene.
In certain embodiments, the ribozyme that nucleic acid is included as catalytic pyrolysis said target mrna transcript and designs, can be used for stoping
The translation of said target mrna and/or the expression of target (see for example PCT Publication case WO 90/11364;With Savall (Sarver) et al.,
1990, science (Science) 247:1222;All it is incorporated herein by reference).
Alternatively or additionally, the expression of endogenous target gene can be by the control region of targeting and target gene (that is, target gene
Promoter and/or enhancer) complementary deoxyribonucleotide sequence reduces, and described targeting is formed and stops target gene in vivo
The triple helices structure of target muscle cell transcription (generally see, Hai Lin (Helene), 1991, Anti-Cancer Drug Design
(Anticancer Drug Des.) 6:569;Hai Lin (Helene) et al., 1992, NYAS's record event (Ann,
N.Y.Acad.Sci.) 660:27;With horse strategic point (Maher), 1992, bioassay (Bioassays) 14:807;All to quote
Mode be incorporated herein).
In certain embodiments, bioactivator is nourishing healthy agent.In certain embodiments, described nourishing healthy agent carries
It is worth for basal nutrient.In certain embodiments, nourishing healthy agent provides healthy or medical benefit.In certain embodiments, battalion
Foster health-care agent is dietary supplement.
In certain embodiments, nourishing healthy agent is vitamin.In certain embodiments, vitamin is following one or
More than Zhong: vitamin A (retinoid), vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), dimension
Raw element B5 (pantothenic acid), vitamin B6 (Benadon), vitamin B7 (biotin), FA (folic acid), vitamin B12 (cyanogen cobalt
Amine element), vitamin C (ascorbic acid), vitamin D, vitamin E or vitamin K.
In certain embodiments, nourishing healthy agent is mineral.In certain embodiments, mineral is following one or
More than Zhong: bismuth, boron, calcium, chlorine, chromium, cobalt, copper, fluorine, iodine, ferrum, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, rubidium, selenium, silicon, sodium, strontium, sulfur, tellurium,
Titanium, tungsten, vanadium or zinc.
In certain embodiments, nourishing healthy agent is essential amino acids.In certain embodiments, aminoacid is following one
Or more than one: arginine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, Soviet Union
Propylhomoserin, tryptophan or valine.
In certain embodiments, nourishing healthy agent can include fatty acid and/or omega-fatty acid (such as DHA or ARA), water
Fruit and vegetable extract, phylloxanthin, Phosphatidylserine, thioctic acid, melatonin, glucamine, chrondroitin, aloe vera (aloe
Vera), India's Gu Artemisia (guggul), green tea, lycopene, Organic food (whole food), food additive, medical herbs, plant
Thing nutrient, antioxidant, the flavonoid components of fruit, Radix Oenotherae erythrosepalae oil, Semen Lini oil, fish oil and marine animal oil (such as cod
Fish oil) and probiotic bacteria.In certain embodiments, nourishing healthy agent can include through genetically engineered and have required character
Bioengineered food (also referred to as " medicine food (pharmafood) ").
Exemplary nourishing healthy agent and dietary supplement are such as at Luo Baici (Roberts) et al. (nutrient and healthcare products: supplement
Encyclopedia (the Nutriceuticals:The Complete Encyclopedia of agent, medical herbs, vitamin and dietetic food
OfSupplements, Herbs, Vitamins, and Healing Foods), NNFA of the U.S. (American
NutriceuticalAssociation), 2001;Be incorporated herein by reference) in have disclosed.Nourishing healthy agent and
Dietary supplement is reference manual-supplementary (Physicians ' Desk Reference on doctor's table
NutritionalSupplements), the 1st edition, 2001 and doctor's table on reference manual-Chinese medicine (Physicians ' Desk
Reference forHerbal Medicines), the 1st edition, in 2001 (being all incorporated herein by reference) the most
Disclose.
In certain embodiments, the nanoparticle loading nourishing healthy agent of the present invention can be incorporated in food.Citing comes
Say, can will load the nanoparticle dissolution of nutrient and healthcare products in the liquid such as such as beverage.
In certain embodiments, bioactivator is cosmetic and/or bentoquatam agent.In certain embodiments, change
Adornment with and/or bentoquatam agent can include vitamin and its derivant (such as vitamin E and its ester, vitamin C and its ester,
Vitamin B, retinol or retinol and its ester), provitamin (such as pantothenylol, nicotiamide or ergocalciferol), antioxygen
Agent, phenol system compound (such as benzoyl peroxide), quintessence oil, wetting agent, sunscreen, humidizer, protein, ceramide and
Pseudoceramide.
In certain embodiments, bioactivator can be that one or more botulinum toxin peptides or protein are combined
Thing.In certain embodiments, botulinum toxin can be botulinum toxins serotypes A, B, C1、C2, one in D, E, F or G or one
Above.In certain embodiments, botulinum toxin can be separated and/or purified botulinum toxin.In certain embodiments,
Botulinum toxin can be through being partially separated and/or through partially purified botulinum toxin.In certain embodiments, botulinum toxin is permissible
It it is natural meat poisoning complex.In certain embodiments, botulinum toxin can be associated with non-toxin proteins.In certain embodiments,
Botulinum toxin can be the botulinum toxin that restructuring prepares.
Those skilled in the art will realize that this is that the exemplary of bioactivator is enumerated rather than comprehensive list.Any
Bioactivator all can be encapsulated in nanoparticle or be bound to the surface of nanoparticle.
Release retardant
In some embodiments of the present invention, especially those contain one or more bioactivators (such as without repairing
Decorations peptide) embodiment in, the nanoparticle compositions of the present invention farther includes one or more hangover compositions
Or allocate with one or more hangover compositions to allow medicament controlled release.Known any release in art
Postpone composition and be suitable for preparing the nanoparticle of the present invention.In certain embodiments, hangover composition be hydrophilic and/
Or hydrophobic polymer.Hangover composition includes (such as) cellulose or derivatives thereof, acrylic acid series polymeric compounds, polyisocyanate polyaddition
Thing, polymer, natural gum, other natural polymer and/or the combination of these materials based on vinyl-pyrrolidinone.
In certain embodiments, described hangover composition is cellulose or derivatives thereof.In certain embodiments, described
Cellulose or derivatives thereof comprise hydroxypropyl methyl cellulose, methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose,
One or more in Cellulose ethyl hydroxypropyl ether, hydroxy ethyl cellulose and hydroxypropyl cellulose.In some embodiment
In, cellulose or derivatives thereof is methylcellulose or derivatives thereof.In certain embodiments, cellulose or derivatives thereof is hydroxyl
Propyl methocel (hydroxypropyl methylcellulose, HPMC).It will be understood by one of ordinary skill in the art that can
Use other cellulosic polymer, including other alkyl cellulose polymers.
In certain embodiments, hangover composition is acrylic acid series polymeric compounds.In certain embodiments, acrylic acid series gathers
Compound includes (such as) acrylic acid and methacrylic acid copolymer, methylmethacrylate copolymer, methacrylic acid ethyoxyl
Ethyl ester, methacrylic acid cyanaoethyl methacrylate, methacrylic acid amino alkyl ester copolymer, poly-(acrylic acid), poly-(methacrylic acid), first
Base acrylic acid alkyl amide copolymer, poly-(methyl methacrylate), poly-(methacrylic anhydride), methyl methacrylate, poly-
Methacrylate, poly-(methyl methacrylate) copolymer, polyacrylamide, methacrylic acid amino alkyl ester copolymer, first
Base glycidyl acrylate copolymer and the combination comprising one or more above-mentioned polymer.Described acrylic polymeric
Thing can comprise the acrylate of the quaternary ammonium group with low content and the full polymerized copolymers of methacrylate.
In certain embodiments, hangover composition is polyester.In certain embodiments, polyester includes (such as) poly-alkylene
Base glycol, PLGA, Pegylation poly-(lactic-co-glycolic acid), poly-(lactic acid), Pegylation
Poly-(lactic acid), poly-(glycolic), Pegylation poly-(glycolic), polylactic acid and the copolymer of polyglycolic acid and its derivant.
In certain embodiments, polyester includes (such as) condensing model, poly-(ortho esters), Pegylation poly-(ortho esters), poly-(oneself is interior
Ester), Pegylation poly-(caprolactone), polylysine, Pegylation polylysine, poly-(ethylenimine), Polyethylene Glycol
Change poly-(ethylenimine) and its derivant.In certain embodiments, polyester can include (such as) polycaprolactone, poly-(L-third hands over
Ester-co-1B), poly-(serine ester), poly-(CHP ester), poly-[α-(4-aminobutyl)-L-ethanol
Acid] and its derivant.
In certain embodiments, hangover composition is the cross linked polymer of poly-(vinyl-pyrrolidinone).Real at some
Executing in example, described polymer is polyvinylpolypyrrolidone.In certain embodiments, polymer is uncrosslinked poly-(ethenyl-pyrrolidine
Ketone).In certain embodiments, polymer is polyvidone.
In certain embodiments, hangover composition can be natural polymer.In certain embodiments, described natural poly-
Compound is natural gum, including (such as) xanthan gum, alginic acid, POLY-karaya, sodium alginate and/or locust bean gum.Implement at some
In example, natural polymer can be protein (such as albumin), lipid, nucleic acid or carbohydrate.In certain embodiments,
Hangover composition is polyester.In certain embodiments, polyester includes (such as) poly alkylene glycol, poly-(Acetic acid, hydroxy-, bimol. cyclic ester-co-third
Lactide), Pegylation poly-(lactic-co-glycolic acid), poly-(lactic acid), Pegylation poly-(lactic acid), poly-(glycolic), poly-
PEGylation poly-(glycolic), polylactic acid and the copolymer of polyglycolic acid and its derivant.In certain embodiments, polyester includes
(such as) condensing model, poly-(ortho esters), Pegylation poly-(ortho esters), poly-(caprolactone), Pegylation poly-(caprolactone),
Polylysine, Pegylation polylysine, poly-(ethylenimine), Pegylation poly-(ethylenimine) and its derive
Thing.In certain embodiments, polyester includes (such as) polycaprolactone, poly-(L-lactide-co-1B), poly-(serine
Ester), poly-(CHP ester), poly-[α-(4-aminobutyl)-L-glycolic] and its derivant.
In certain embodiments, hangover composition is the cross linked polymer of poly-(vinyl-pyrrolidinone).Real at some
Executing in example, described polymer is polyvinylpolypyrrolidone.In certain embodiments, polymer is uncrosslinked poly-(ethenyl-pyrrolidine
Ketone).In certain embodiments, polymer is polyvidone.In certain embodiments, hangover composition can be natural polymerization
Thing.In certain embodiments, described natural polymer is natural gum, including (such as) xanthan gum, alginic acid, POLY-karaya, Sargassum
Acid sodium and/or locust bean gum.In certain embodiments, natural polymer can be protein (such as albumin), lipid, nucleic acid
Or carbohydrate.
Blender
The nanoparticle compositions of the present invention can be formulated for offeing medicine to individuality.In certain embodiments, the present invention
Nanoparticle compositions is formulated for being applied on skin realize transdermal transfer to described individuality.For example, the present invention
Nanoparticle compositions adjustable be assigned in the cosmetic or other preparation that are intended to local application.
Human skin comprises corium and epidermis.Epidermis has several layer tissue, i.e. horny layer, clear layer, granular layer, spinous layer and
Basal layer (differentiates towards interior order according to from skin appearance).Horny layer is rendered as usual transdermal transfer medicine and may be especially
The most notable obstacle of the peptide that transdermal transfer is the most modified.Horny layer is typically about 10-15 μ m-thick, and it is by being arranged in several layers flat
Flat, keratinocyte (horn cell) composition.Intercellular substance between horn cell is filled with lipid conformation, and can be saturating at material
Cross skin aspect play an important role (Borrow cuts down (Bauerova) et al., 2001, Europe drug metabolism miscellaneous with pharmacokinetics
Will (European Journal of Drug Metabolism andPharmacokinetics), 26:85;With the side quoted
Formula is incorporated herein).
Remainder at horny layer table below skin is about 150 μ m-thick.Corium about 1mm-2mm is thick and is positioned under epidermis
Face.Corium is arranged by various capillary tubies and neuronal process.
Traditionally, the trial to percutaneous administration medicine concentrates in the past always and increases cuticular permeability.Some are attempted
Including using the infiltrative chemical intensifier increasing molecule through skin.Some attempt including using plant equipment to walk around cutin
Layer or excise cuticular part.It addition, attempt including using ultrasound wave or iontophoresis to promote drugs through skin.Greatly
In most cases, target is that medicament (the least molecule) passes skin, generally makes medicament can pass to the capillary tube in corium
Bed, medicament can systemically be incorporated to individual internal to realize response to treatment there.
The method that present invention particularly provides the most modified peptide of percutaneous administration, described method need not use grinding agent or its
Its disrupting agent (either chemistry, machinery, electricity, magnetic etc.).More precisely, present inventor is it has been surprisingly discovered that incorporated herein
Nanoparticle compositions in botulinum toxin can effectively transdermal transfer and make horny layer permeable without other or destroy angle
The step of matter layer.The meat poisoning nanoparticle compositions of described medicament or step and the present invention is used together and need not get rid of at this
Outside bright all embodiments, but it is not required.
Therefore, the nanoparticle compositions that the present invention provides through the local application present invention carrys out the most modified peptide of administration
Method.In certain embodiments, the nanoparticle compositions of the present invention is directly applied on skin and absorbs through epidermal area.?
In some embodiments, the top layer of described nanoparticle compositions skin-permeable, including horny layer, dermal pore and/or cutaneous gland,
And do not use chemically or mechanically skin penetration enhancer or other cause the medicament of grinding.
It will be understood by one of ordinary skill in the art that the compositions of the present invention for topical administration can be prepared as cosmetic and adjust
Join thing, such as toner/smoothing toner, nutritional solution type emulsion, clean skin liquid, cleansing cream, emulsion, milky lotion, massage cream, emollient cream, end adornment liquid,
Lip pomade, facial film or face glue, cleaning agent composite (such as shampoo, purificant, bath gel, hair conditioner or soap) or department of dermatologry group
Compound (such as lotion, ointment, gel, emulsifiable paste, paster or spraying).
The described composite of the nanoparticle compositions of the present invention generally include with one or more such as filleies,
The combination of the excipient such as chelating agen, softening agent, coloured material (such as pigment and dyestuff) and aromatic.
In certain embodiments, the nanoparticle compositions of the present invention is allocated as emulsifiable paste.Term " emulsifiable paste " refers to usual warp
Allotment for be applied on skin can be spreadable compositions.Emulsifiable paste usually contains based on oil and/or the substrate of fatty acid.According to
The present invention allotment emulsifiable paste can containing nanoparticle and can after topical administration (the most described nanoparticle) the most complete
Through skin.Described emulsifiable paste also acts as the supporting agent of be incorporated to material (such as botulinum toxin).
It will be understood by one of ordinary skill in the art that the nanoparticle compositions of the present invention may be incorporated in the devices such as such as paster.
Various transdermal patch structures are that technique is known;It will be understood by one of ordinary skill in the art that the nanometer of the present invention
Particle composition can be readily incorporated into various described structure any one in.In certain embodiments, transdermal patch can enter one
Step comprises the pin of multiple one side extension being affixed on skin from paster, and wherein said pin extends the cutin being projected into skin from paster
Layer.In certain embodiments, described pin does not puncture blood vessel.
In some embodiments of the invention, so that putting in the storage tank during nanoparticle compositions may be provided in paster
The pressure of paster causes the most modified peptide to derive from paster (optionally can pass through pin) and through horny layer.
In some embodiments of the invention, transdermal patch includes sticker.Some examples of adhesive patches are well-known
(for example, with reference to United States Patent (USP) Des.296,006;6,010,715;5,591,767;5,008,110;5,683,712;5,948,
433;With 5,965,154;It is all incorporated herein by reference).Being generally characterised in that of adhesive patches has and will paste
Adhesion coating in individual's skin, for accommodating the storage tank of medicament or bank and the outer surface preventing medicine from spilling from storage tank.
The outer surface of paster is the most inviscid.
It will be understood by one of ordinary skill in the art that transdermal patch only can be used to the nanoparticle subgroup of the administration present invention
One device example of compound.Lift other example several again, can use and be not required to first compositions be applied to (this on the finger of people
Act may produce undesirable paralysis to finger) just can use the device of compositions.Suitably device includes spatula, swab, nothing
Needle injection and adhesive patches.Use spatula or swab etc. may need to insert the device in the container containing compositions.Use
Syringe can realize by filling syringe by compositions.Then compositions can be spreadable by spatula or swab local, or can
Drain into individual's skin from syringe.
In various embodiments of the present invention, it may be necessary to limit the most modified peptide and be only delivered to be intended to delivery areas.
In certain embodiments, described limit transmission and can be come by the nanoparticle compositions of the present invention being used in application device
Realizing, described device allows target site compositions being applied on skin that compositions is not applied to the non-target site of skin
Region.Obviously, transdermal patch can be used for this purpose.Alternatively or additionally, if being only intended to be locally applied to modified peptide
Selected areas, then other region can be covered or pretreatment or carry out other protection so as not to expose.
Illustration
Following instance is merely intended to the explanation of the specific embodiment providing the present invention to be contained.These examples are in no way beaten
Calculate and limit the present invention.
Example 1: five peptide nanoparticles composite
This example provides the peptide nanoparticles compositions comprising nanoemulsions, and described nanoemulsions contains known to skin knot
Structure has bioactive pentapeptide KTTKS (SEQ ID NO.:1) (sheet mountain (Katayama) et al., see on).
The preparation of pentapeptide nanoemulsions preparation is as follows:
800mg soybean oil and 800mg Tween 80 are stirred 5 minutes by sterile vials;
Add and there is the 8.4ml water of 0.0001g peptide KTTTS (SEQ ID NO.:1) and stir 20 minutes;
By homogenizing samples 1 minute;
Stirred sample 20 minutes;And
Under 23,000psi by sample micro fluidicization once.
Use can analyze the Malvern nano-particle size analysis instrument of the particle between about 0.6nm-6000nm
(MalvernNano S particle sizer) assesses the particle diameter of gained pentapeptide nanoemulsions.Described pentapeptide nanoemulsions system
Agent has two particle diameter peaks, mean diameter 106nm (table 2).
The particle diameter distribution of table 2: five peptide nanoparticles
Size range | Particle percent |
10-20nm | 1.3% |
21-100nm | 30.2% |
101-120nm | 10.4% |
121-150nm | 22.4% |
151-200nm | 19.3% |
201-300nm | 14.7% |
301-400nm | 1.7% |
Amount to | 100.0% |
Example 2: five peptide nanoparticles composite and transdermal penetration and biological effect
This example provides and comprises the peptide nanoparticles of nanoemulsions, and described nanoemulsions contains and known has skin texture
Bioactive pentapeptide KTTKS (SEQ ID NO.:1) (sheet mountain (Katayama) et al., see on;It is herein incorporated by reference this
In literary composition).This example proves the applied dermally peptide nanoparticles (being KTTKS (SEQ ID NO.:1) in the case) life to skin
Thing effect.
Material and method
The preparation of pentapeptide nanoemulsions preparation is as follows:
5.6g granny rag traction therapy WL 1349 oil and 5.6g Tween 80 are stirred 5 minutes by sterile beaker;
58.8g SILVER REAGENT water is placed in independent beaker;0.010g peptide KTTTS (SEQ ID NO.:1) is added described
In water and stirring 20 minutes;
The inclusions of the first beaker added in the inclusions (that is, water and peptide) of described beaker and be followed by stirring for 20 points
Clock;And
Under 23,000psi by whole sample micro fluidicization once.
Use can analyze the Malvern nano-particle size analysis instrument of the particle between about 0.6nm-about 6000nm
(Malvern Nano S particle sizer) assesses the particle diameter of gained pentapeptide nanoemulsions.Described pentapeptide nanoemulsions
Preparation has the mean diameter of 114.4nm.The particle size of about 95% is less than 130nm.
Then by pentapeptide nanoemulsions and isopyknic protective skin cream (light color PCCA vanishing cream (Base PCCA
VanishingCream Light)) mixing and then vortex uniformly emulsifiable paste to obtain " process emulsifiable paste ".
Except during the course without peptide, preparing " comparison emulsifiable paste " by the method identical with processing emulsifiable paste.
Buy ten Si Weisiweibosite (Swiss Webster) mice, every body weight about 20 grams.After arrival, make institute
There are animal (defined below, to be grouped stable breeding, often organize 5 mices of every cage) and the outfit standard cage bedding and padding that adapt to its cage one week
5001 (Purina 5001) feedstuff is received with Puri.After one week, the following example that processes of application:
Process example
1st group (comparison): every day, lasts 8 weeks, is applied in 5 mices by 75 μ l comparison emulsifiable pastes with glove finger
The back of each is until can't see emulsifiable paste.Process for the first time and a few days ago and hereafter with one week for interval shaver scrape off
The hair of mouse back.
2nd group (process): every day, lasts 8 weeks, with glove finger, 75 μ l is processed emulsifiable paste and is applied in 5 mices
The back of each is until can't see emulsifiable paste.Process for the first time and a few days ago and hereafter with one week for interval shaver scrape off
The hair of mouse back.
Assessment
Use by oneself in the future and compare emulsifiable paste or process the vitrification of each mouse back that emulsifiable paste processed and then with Mason three
Color histological stain (Masson ' s Trichrome histologic stain) processes.Use 1 to the 4 of staining power
Histological grades, under the amplification of 400 times, assessment staining power: 1=is almost without dyeing, and collagen fibril is very thin, 2=
Seldom dyeing and the least collagen fibril width, 3=moderate stain and medium fibril width, and 4=dye strongly and width is former
Fiber.
Result
Histological assessment
2.33 in matched group by the Mean histology score of skin histology of Mason's trichrome staining dyeing, the highest can
Can score 4.Under Bi compare, the Mean histology score of process group small mouse stain skin is 3.67, highest possible score 4.This
The collagen protein staining power of expression process group increases by 57% relative to matched group.See Fig. 1, matched group and process group each
The microphotograph example of skin histology sample.
The assessment of skin thickness effect
After the histological cross sections checking mouse back skin that is sliced and that be placed on glass slide, use and measure respectively
Skin thickness test (Skin Layer Thickness Test) of the degree of depth (in terms of mm) of cortex measures the thickness of skin thickness
Degree.
The assessment that extracellular matrix produces
Collagen protein is the key component of the inclusions of extracellular matrix.Mice that is sliced and that be placed on glass slide
In two independent tests of skin of back, use two kinds of independent collagen tissue dyeing (Picro-Sirius red (Picro
SiriusRed) and rosewood (Pterocarpus Osun)) assess collagen content.
By using the hydroxyl dried meat ammonia of the homogenizing preparation of immunoblotting (Western Blot) technology for detection mouse back skin
Acid content assesses collagen content.Hydroxyproline content represents collagen content.
Conclusion
Result shows, by Histological assessment, the collagen protein of process group is more than matched group statistically.These
Contrasting data shows, locally pentapeptide nanoemulsions preparation is with compared with the comparison emulsifiable paste of described pentapeptide, has skin and can measure
Biological effect.Previously research has shown that described peptide cannot permeate intact skin (sheet mountain (Katayama) under without chemical modification
Et al., see on).Therefore, these data show, the nanoemulsions composite of the present invention enables the most modified peptide to permeate, from
And skin is produced the effect consistent with the known biological agent of peptide: increase the collagen protein in skin and produce and caused
Skin thickness increases.
Expected results shows, the skin of process group is thicker than matched group statistically.Expected results shows, process group
Collagen protein averagely more than matched group statistically, and as by two kinds of histological stains and the immunoblotting of hydroxyproline
Measured by measurement method.
Example 3: the skin reached mice by applied dermally peptide nanoparticles is thickening and extracellular matrix stimulating effect:
The effect of the peptide of variable concentrations in nanoparticle
This example proves to change the concentration of peptide in nanoparticle to the applied dermally peptide nanoparticles biological effect to skin
Impact.
Material and method
Repeat the experiment described by example 3, be decreased or increased with multiple 10 except processing the concentration of peptide in emulsifiable paste.
Result and conclusion
Expected results shows, those are average statistically than that with the skin of the mice that the peptide concentration increasing by 10 times processes
The mice that the peptide concentration of a little increases processes is thick.Expected results shows, those mices processed with the peptide concentration increasing by 10 times
Collagen protein is average more than those mices processed with the peptide concentration reduced the most statistically, as by two kinds of histological stains and
Measured by the immunoblotting measurement method of hydroxyproline.On the whole, it is contemplated that these contrasting datas show, peptide nanoemulsions is to skin
Biological effect change depending on the concentration of peptide that is incorporated to.
Example 4: to human individual's administration five peptide nanoparticles to reduce skin lines
This example proves the applied dermally peptide nanoparticles biological effect to human skin.
Material and method
Prepare the pentapeptide nanoemulsions according to example 1 or 2 preparation, and with isopyknic protective skin cream (light color PCCA vanishing cream)
Mixing and then vortex uniformly emulsifiable paste are to obtain " process emulsifiable paste ".
By will pentapeptide same amount of with example 1 be mixed in same amount of water and then and be used for preparing process emulsifiable paste
Same amount of protective skin cream vortex together prepares " non-nano process emulsifiable paste ".
By will water same amount of with example 1 or 2 and together with being used for preparing the process same amount of protective skin cream of emulsifiable paste vortex
Prepare " comparison emulsifiable paste ".
30 are had the healthy human of notable facial lines (such as observing in the people have photo damaged skin)
Body includes the half of face research that double blinding, placebo, left and right are random in.All individualities are all by observation unwitting to disposition
Person uses five point scale classification.The score 0 of described grade is normal skin, and score 5 is that serious facial lines and wrinkle are (mainly at eye
Week or " crows-feet " district).Also with regard to pore size (little to big) and smoothness (light slides into coarse/coarse groove) aspect assessment buccal skin
Texture.Only include more than 2.5 or 2.5 individuality of initial inspection score in.Normalized version and distance and lighting condition pair will be used
Individual face photograph.
Process example
Patient agrees to not use any face protection product 3 weeks, and except comparison emulsifiable paste, it can be spaced and use 12 hour every day
Twice.At this initial " cleaning " after date, indicating " right " and the emulsifiable paste of " left " to each patient two pipe, each pipe digital code is unique.
Instruct patient's face on the right to use right pipe to use left pipe at left side face, be spaced 12 hour every day twice.Instruct patient by " Semen Pisi sativi
Size " emulsifiable paste (about 0.4g) measured is applied to every limit face.Also instruct patient can not use other face protection product.10 individualities
(matched group) right pipe contains comparison emulsifiable paste and left pipe contains comparison emulsifiable paste.10 right pipes of individuality (non-nano process group) contain comparison
Emulsifiable paste and left pipe contain non-nano and process emulsifiable paste.10 right pipes of individuality (nanometered disposal group) contain comparison emulsifiable paste and left pipe contains and receives
Rice processes emulsifiable paste.
Assessment
After clean after date starts processing scheme when 4,8 and 12 weeks, individuality is observed and takes a picture.It addition, to individuality
The unwitting observer of disposition and individual oneself by above-mentioned grade to the right face and each flaw-piece skin stricture of vagina of left side face
Reason is given a mark.
Result and conclusion
Expected results shows, the difference between right side and the left side face texture score of nanometered disposal group is average statistically
More than the difference (display skin appearance improves) between matched group and the right side of non-nano process group and left side score.On the whole,
Expect that these contrasting datas show, with without described pentapeptide comparison emulsifiable paste and have not in nanoparticle composite identical five
The simple emulsifiable paste (non-nano emulsifiable paste) of peptide is compared, and locally pentapeptide nanoemulsions preparation has measurable cosmetic effect to skin.
Equivalent and scope
Foregoing relate to the description of some non-limitative preferred embodiment of the present invention.Those skilled in the art will recognize
Know or can only use normal experiment to determine many equivalents of only certain embodiments of the present invention described herein.Affiliated neck
Skill will appreciate that of territory, in the situation without departing from the spirit or scope of the present invention as defined in additional claims
Under, this description can be carried out variations and modifications.
In detail in the claims, unless the contrary indicated otherwise or from the context it is clear that the most such as " one " and " institute
State " etc. word can refer to one or more than one.Unless the contrary indicated otherwise or from the context it is clear that otherwise in a group one
Include claim or the description of "or" between individual or more than one member, be considered as meeting in given product or method and exist, adopt
With one, more than one or whole group members, or one, more than one or all group member and given product or method
Relevant.The present invention includes existing in given product or method, using just what a group member, or just what a group member
The embodiment relevant with given product or method.Present invention additionally comprises in given product or method exist, use more than one or
All group members, or the embodiment that more than one or whole group member is relevant with given product or method.Additionally, answer
Solve, the present invention contain the relevant portion of one or more claims or description one or more limit,
Key element, clause, descriptive term etc. introduce all changes in another claim, combination and permutation.For example, any attached
The claim belonging to another claim can be modified to include other right any being attached to the requirement of same fundamental right
One or more seen in requirement limit.Additionally, when claims describe compositions, it should be understood that unless otherwise
Indicate or unless those skilled in the art obviously will appear from contradiction or inconsistent, otherwise include for disclosed herein
Purpose and the method that uses described compositions, and include according to known in preparation method disclosed herein or art
Any one in other method prepares the method for described compositions.For example, it should be understood that any compositions of the present invention can
For suppress any position and/or by discussed herein or art in the shape of adhesion caused by known any reason
Become, be in progress and/or recur.Should also be clear that according to any compositions obtained by the method for preparation compositions disclosed herein
Can be used for suppressing any position and/or by the adhesion caused by known any reason in discussed herein or art
Formed, be in progress and/or recur.It addition, the present invention contains according to obtained by any method of preparation compositions disclosed herein
Compositions.
When to enumerate form, such as when providing key element with Markush group (Markush group) form, it should be understood that also take off
Show each subgroup of described key element, and any key element can be removed from group.Should also be noted that term " comprises " it is intended that open
Formula and allow to include other key element or step.It will be appreciated that in general, when the aspect of the present invention or the present invention is specific to comprise
When key element, feature, step etc. are mentioned, some embodiment of the aspect of the present invention or the present invention is by described key element, feature, step etc.
Form or be substantially made up of described key element, feature, step etc..For the sake of simple, the most specifically state those
Embodiment.Therefore, for each embodiment that the present invention comprises one or more key elements, feature, step etc., this
Invention also provides for the enforcement being made up of those key elements, feature, step etc. or being substantially made up of those key elements, feature, step etc.
Example.
When providing scope, end points is included.Further, it should be appreciated that unless otherwise directed or additionally from context and/or
It is clear that the value otherwise stated with range format can be assumed that the difference as the present invention in the understanding of those skilled in the art
Any particular value in prescribed limit in embodiment, unless the most additionally clear stipulaties, otherwise reaches 1/10th of range lower limit.
Should also be clear that unless otherwise directed or additionally from the understanding of context and/or those skilled in the art it is clear that no
Then with scope express value can be assumed that as given range in any subrange, wherein the end points of subrange with described scope
/ 10th identical precision of lower limit are expressed.
Further, it should be appreciated that any specific embodiment of the present invention can be arranged from any one or more than one claim clearly
Remove.The compositions of the present invention and/or any embodiment of method, key element, feature, application or aspect (the most any peptide, any peptide
Modification, any nanoparticle, any nanoemulsions, any surfactant, any Premix Component oily, any, any preparation
The method of nanoemulsions, any Therapeutic Method etc.) can get rid of from any one or more than one claim.For simplicity,
Eliminating one or more key elements, feature, purpose or all embodiments of aspect are not explicitly stated herein.
Sequence table
<110>Anterios Inc.
<120>peptide nanoparticles and its purposes
<130>2007339-0016
<140>PCT/US2007/086040
<141>2007-11-30
<160>14
<170>PatentIn version 3.5
<210>1
<211>5
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>1
Lys Thr Thr Lys Ser
1 5
<210>2
<211>10
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>2
Glu Tyr Lys Thr Thr Lys Ser Ser Arg Leu
1 5 10
<210>3
<211>8
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>3
Val Ile Glu Tyr Lys Thr Thr Lys
1 5
<210>4
<211>4
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>4
Lys Thr Thr Lys
1
<210>5
<211>12
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>5
Gly Lys Thr Val Ile Glu Tyr Lys Thr Thr Lys Ser
1 5 10
<210>6
<211>15
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>6
Gly Lys Thr Val Ile Glu Tyr Lys Thr Thr Lys Ser Ser Arg Leu
1 5 10 15
<210>7
<211>20
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>7
Trp Gly Lys Thr Val Ile Glu Tyr Lys Thr Thr Lys Ser Ser Arg Leu
1 5 10 15
Pro Ile Ile Asp
20
<210>8
<211>20
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>8
Cys Thr Ser His Thr Gly Ala Trp Gly Lys Thr Val Ile Glu Tyr Lys
1 5 10 15
Thr Thr Lys Ser
20
<210>9
<211>4
<212>PRT
<213>artificial sequence
<220>
<223>peptide that extracellular matrix produces can be promoted
<400>9
Thr Thr Lys Ser
1
<210>10
<211>6
<212>PRT
<213>artificial sequence
<220>
<223>peptide of wrinkle can be reduced
<400>10
Glu Glu Met Gln Arg Arg
1 5
<210>11
<211>6
<212>PRT
<213>artificial sequence
<220>
<223>peptide of wound healing can be improved
<400>11
Val Gly Val Ala Pro Gly
1 5
<210>12
<211>6
<212>PRT
<213>artificial sequence
<220>
<223>peptide of wound healing can be improved
<400>12
Tyr Tyr Arg Ala Asp Ala
1 5
<210>13
<211>3
<212>PRT
<213>artificial sequence
<220>
<223>peptide of wound healing can be improved
<400>13
Gly His Lys
1
<210>14
<211>14
<212>PRT
<213>artificial sequence
<220>
<223>peptide of extracellular matrix excess accumulation can be treated
<400>14
Thr Ser Leu Asp Ala Ser Ile Ile Trp Ala Met Met Gln Asn
1 5 10
Claims (38)
1. comprise a nanoemulsions for a group particle, wherein the particle more than 50% have between 10 nanometers and 300 nanometers it
Between diameter, the mean diameter of wherein said particle is in the range of 50 nanometers to 250 nanometers, and wherein this group of particles is maximum straight
Difference between footpath and minimum diameter is less than 600nm, and wherein said nanoemulsions comprises at least one oil, one or more tables
Face activating agent, water and the most modified peptide, described peptide is formed by selected from following aminoacid sequence: EYKTTKSSRL,
GKTVIEYKTTKS, GKTVIEYKTTKSSRL, WGKTVIEYKTTKSSRLPIID or CTSHTGAWGKTVIEYKTTKS;
The ratio of wherein said surfactant and oil is by weight in the range of between 0.25:1 and 3:1;
Wherein said oil comprises one or more fatty acid groups or its salt;And
Wherein said surfactant is selected from the group consisted of: phosphoglyceride;Phosphatidylcholine;Two palmityl phospholipid
Phatidylcholine (DPPC);DOPE (DOPE);Dioleoyl epoxide propyl group three second ammonium (DOTMA);Dioleoyl phospholipid
Phatidylcholine;Cholesterol;Cholesteryl ester;DG;DG succinate;Diphosphatidylglycerol (DPPG);16
Alkanol;Fatty alcohol;Polyoxyethylene-9-Laurel ether;Fatty acid;Fatty mono glyceride;Fatty acid diglyceride;Fatty acid acyl
Amine;Sorbitan trioleate (Si Pan (Span) 85) glycocholate;Sorbitan monolaurate (this Pan 20);
TWEEN-20 (tween (Tween)-20);Polysorbate 60 (Tween-60);Polysorbate 65 (Tween-65);Poly-mountain
Pears acid esters 80 (tween 80);Polysorbate 85 (tween 85);Polyoxyethylene monostearate;Surfactin
(surfactin);Poloxamer (poloxomer);Sorbitan fatty acid esters;Lecithin;LYSOLECITHIN SUNLECITHIN A;Phosphatidyl
Serine;Phosphatidylinositols;Sphingomyelins;PHOSPHATIDYL ETHANOLAMINE (cephalin);Cuorin;Phosphatidic acid;Cerebroside;Di(2-ethylhexyl)phosphate spermaceti
Ester;DPPG;Stearylamine;Dodecyl amine;Cetylamine;Acetyl palmitate;Glycerol ricinoleate;
Cetyl stearic;Isopropyl myristate;Tyloxapol (tyloxapol);PEG 5000-phosphatidyl ethanol
Amine;PEG 400-monostearate;Phospholipid;There is synthesis and/or the natural detergent of high surfactant characteristic;De-
Oxycholic acid salt;Cyclodextrin;Chaotropic salt;And ion-pairing agent.
Nanoemulsions the most according to claim 1, wherein the particle more than 50% have between 10 nanometers and 250 nanometers it
Between diameter range.
Nanoemulsions the most according to claim 1, wherein the particle more than 50% have between 10 nanometers and 200 nanometers it
Between diameter range.
Nanoemulsions the most according to claim 1, wherein the particle more than 50% have between 10 nanometers and 150 nanometers it
Between diameter range.
Nanoemulsions the most according to claim 1, wherein the particle more than 50% have between 10 nanometers and 120 nanometers it
Between diameter range.
Nanoemulsions the most according to claim 1, wherein the particle more than 50% have between 10 nanometers and 100 nanometers it
Between diameter range.
Nanoemulsions the most according to claim 1, wherein the particle more than 50% have between 10 nanometers and 50 nanometers it
Between diameter range.
Nanoemulsions the most according to claim 1, wherein said nanoemulsions comprises a kind of oil, at least one surface activity
Agent, water and the most modified peptide.
Nanoemulsions the most according to claim 1, wherein said nanoemulsions comprises at least one surface activity oily, a kind of
Agent, water and the most modified peptide.
Nanoemulsions the most according to claim 1, wherein said grease separation is from the group consisted of: almond oil
(almond oil), Fructus Pruni nucleolus oil (apricot kernel oil), American Avocado Tree oil, babassu oil, oleum bergamottae, seed of black currant
Oil, borage oil, cade oil, Chamomile oil, Canola oil, caraway oil, babassu oil, Oleum Ricini, Oleum Cinnamomi, cupu oil,
Oleum Cocois, code-liver oil, coffee bean oil., Semen Maydis oil, Oleum Gossypii semen, fat of Oromaius norvaehollandeae, Eucalyptus oil, Radix Oenotherae erythrosepalae oil, fish oil, Semen Lini oil, Herba Pelargonii Graveolentis
Alcohol oil, calaba oil, Oleum Vitis viniferae, hazelnut oil, oil of hyssop, jojoba, Hawaii kernel oil (kukui nut oil), lavandin
Oil, Essential lavender oil, Fructus Citri Limoniae oil, litsea cubeba oil (litsea cubeba oil), macadimia nut oil (macademia nut oil),
Radix Malvae sylvestris oil, Fructus Mangifera Indicae seed awns flower seed oil oily, white, ermine oil, Semen Myristicae oil (nutmeg oil), olive oil, oleum Citri sinensis, bathypelagic fish oil
(orange roughy oil), Petiolus Trachycarpi oil, palm-kernel oil, peach kernel oil, Oleum Arachidis hypogaeae semen, poppy seed oil, Semen Cucurbitae oil, rapeseed oil, rice
Rice oil, oil of rosemary, safflower oil, Oleum Santali albi, Flos Camelliae Japonicae caul-fat (sasquana oil), savory oil, Oleum Hippophae, Oleum sesami, breast
Wood fruit oil, silicone oil, soybean oil, Oleum helianthi, tea tree oil, Ji oil, Camellia oil (tsubaki oil), vetiver oil, Oleum Juglandis and
Semen Tritici aestivi germ oil;Butyl stearate;Trivent OCG;Tricaprin;Cyclomethicone
(cyclomethicone);Ethyl sebacate;Simethicone 360 (dimethicone 360);Isopropyl myristate;Ore deposit
Thing oil;Octyldodecanol;Oleyl alcohol;Silicone oil;Short chain triglyceride;Medium chain triglyceride;Granny rag traction therapy WL 1349
(Labrafac WL 1349);Long chain triglyceride;Its saturated oils;With its unsaturated oils.
11. nanoemulsions according to claim 1, wherein said fatty acid is surface active fatty acid.
12. nanoemulsions according to claim 1, wherein fatty alcohol is Polyethylene Glycol (PEG).
13. nanoemulsions according to claim 1, wherein surface active fatty acid is Palmic acid or oleic acid.
14. nanoemulsions according to claim 1, wherein sorbitan fatty acid esters is sorbitan three oil
Acid esters.
15. nanoemulsions according to claim 1, wherein surfactant is 0.5:1 with the ratio of oil by weight.
16. nanoemulsions according to claim 1, wherein surfactant is 1:1 with the ratio of oil by weight.
17. nanoemulsions according to claim 1, wherein surfactant is 2:1 with the ratio of oil by weight.
18. according to the nanoemulsions described in any claim in claim 1-17, and wherein it comprises at least one further
The additional component of emulsifiable paste, oil, ointment, gel, spraying, lip pomade or sunscreen is formed together with described nanoemulsions.
19. comprise transparent according to the nanoemulsions described in any claim in claim 1-17, wherein said nanoemulsions
Matter acid.
20. 1 kinds of purposes according to the nanoemulsions described in any claim in claim 1-19, it is used for manufacturing local
It is applied in individual's skin make up or the compositions of therapeutic benefit to obtain.
21. purposes according to claim 20, wherein said compositions is used for making skin or subcutaneous tissue thickening;For controlling
Treat, alleviate, improve, alleviate skin lines, postpone the generation of skin lines, the progress of suppression skin lines, reduction skin lines
Seriousness or reduce skin lines incidence rate;For improving individual's skin outward appearance;For maintaining individual's skin outward appearance;For
Treat, alleviate, improve, alleviate wound, the progress of suppression wound or reduce the seriousness of wound;For treating, alleviate, improving,
Alleviate at least one symptom relevant to following disease, postpone described symptom generation, suppress described symptom progress, reduce institute
The seriousness stating symptom or the medicine of the incidence rate reducing described symptom: hypertrophic cicatrix, keloid, limitation sclerosis, be
System property sclerosis or be characterized as other condition of illness of extracellular matrix excess accumulation.
22. purposes according to claim 21, wherein said skin lines is wrinkle of skin.
23. purposes according to claim 21, the step wherein used is performed by following: hands;Adhesive patches;Spatula;
Swab;Needleless injector;Or device, described device allow to be applied to described nanoemulsions the target site of described skin and not
Described nanoemulsions is applied to the non-target site of described skin.
24. purposes according to claim 23, wherein said hands is glove finger or unguarded finger.
25. purposes according to claim 21, the described the most modified peptide of at least a part of which 1% permeates described skin.
26. purposes according to claim 21, the described the most modified peptide of at least a part of which 10% permeates described skin.
27. purposes according to claim 21, the described the most modified peptide of at least a part of which 25% permeates described skin.
28. purposes according to claim 21, the described the most modified peptide of at least a part of which 50% permeates described skin.
29. purposes according to claim 21, the described the most modified peptide of at least a part of which 75% permeates described skin.
30. purposes according to claim 21, the described the most modified peptide of at least a part of which 90% permeates described skin.
31. purposes according to claim 21, the described the most modified peptide of at least a part of which 95% permeates described skin.
32. purposes according to claim 21, the described the most modified peptide of at least a part of which 99% permeates described skin.
33. purposes according to claim 21, the most modified wherein said peptide all permeates described skin.
34. 1 kinds of methods, it comprises the steps of
A kind of pre-composition comprising oil, surfactant, water and the most modified aminoacid sequence peptide containing KTTKS is provided;With
Reach the time according to the nanoemulsions described in any claim in claim 1 to 19 and under the conditions of make described pre-
Mixed thing stands high shear force or high pressure homogenization;Wherein high shear force or high pressure homogenization are to realize optionally by microfluidization.
35. methods according to claim 34, in wherein said pre-composition, the ratio of oil and surfactant is by weight
In the range of between 0.25:1 and 3:1.
36. methods according to claim 35, wherein oil is 0.5:1 with the ratio of surfactant by weight.
37. methods according to claim 35, wherein oil is 1:1 with the ratio of surfactant by weight.
38. methods according to claim 35, wherein oil is 2:1 with the ratio of surfactant by weight.
Priority Applications (1)
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CN201611075414.6A CN107080703A (en) | 2006-12-01 | 2007-11-30 | Peptide nanoparticles and its purposes |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US87220606P | 2006-12-01 | 2006-12-01 | |
US60/872,206 | 2006-12-01 | ||
PCT/US2007/086040 WO2008140594A2 (en) | 2006-12-01 | 2007-11-30 | Peptide nanoparticles and uses therefor |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN201611075414.6A Division CN107080703A (en) | 2006-12-01 | 2007-11-30 | Peptide nanoparticles and its purposes |
Publications (2)
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CN101917959B true CN101917959B (en) | 2016-12-14 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104922063A (en) * | 2014-03-19 | 2015-09-23 | 纳米及先进材料研发院有限公司 | Nano-emulsion used for transdermal drug delivery and method for preparing the same |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2849375A1 (en) * | 2002-12-30 | 2004-07-02 | Jean Noel Thorel | Cosmetic or dermatological skin-treatment composition, useful e.g. for protection against light-induced aging, comprises a complex of a peptide or protein with a nucleotide or nucleic acid |
CN1582302A (en) * | 2001-10-30 | 2005-02-16 | 彭特法姆股份公司 | Dermopharmaceutically and cosmetically active oligopeptides |
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1582302A (en) * | 2001-10-30 | 2005-02-16 | 彭特法姆股份公司 | Dermopharmaceutically and cosmetically active oligopeptides |
FR2849375A1 (en) * | 2002-12-30 | 2004-07-02 | Jean Noel Thorel | Cosmetic or dermatological skin-treatment composition, useful e.g. for protection against light-induced aging, comprises a complex of a peptide or protein with a nucleotide or nucleic acid |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104922063A (en) * | 2014-03-19 | 2015-09-23 | 纳米及先进材料研发院有限公司 | Nano-emulsion used for transdermal drug delivery and method for preparing the same |
CN104922063B (en) * | 2014-03-19 | 2019-06-18 | 纳米及先进材料研发院有限公司 | Nanoemulsions and its manufacturing method for percutaneous dosing |
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