CN104231048A - Hair growth peptide and pharmaceutical composition - Google Patents
Hair growth peptide and pharmaceutical composition Download PDFInfo
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- CN104231048A CN104231048A CN201410157862.5A CN201410157862A CN104231048A CN 104231048 A CN104231048 A CN 104231048A CN 201410157862 A CN201410157862 A CN 201410157862A CN 104231048 A CN104231048 A CN 104231048A
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- hair tonic
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- victory peptide
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Abstract
The invention relates to a hair growth peptide for hair growth and a pharmaceutical composition. Specifically, the pharmaceutical composition comprises germinal peptide (HGP), wherein the germinal peptide (HGP) is a whole sequence or a partial sequence of an amino acid sequence SEQ ID No: 1. The method for growing hair comprises administering a growing hair peptide (HGP) to a subject, wherein the growing hair peptide (HGP) is the complete sequence or a partial sequence of the amino acid sequence SEQ ID No: 1.
Description
Technical field
The present invention relates to a kind of the hair tonic victory peptide and the pharmaceutical composition that are applied to hair tonic.
Background technology
Baldness (alopcia) is reduced by the reduced number of the hair in the vegetative period (anagen) being in hair cycles (hair cycle) and the abnormal hair be in caused by the catagen (catagen) of hair cycles or the number increase of the hair of resting stage (telogen).Although not yet clearly disclose the mechanism of baldness, but baldness generally can be caused by following reason: by endocrine system disorder (endocrine disorder) (such as hormone imbalances (hormone unbalance)), autonomic nervous system disorder (autonomic nerves disorder) or the excess sebum (sebum) caused by recycle system disorder (circular disorder) (such as blood circulation disorder (abnormal blood circulation)) produce, scalp functional deterioration caused by fungi, allergy, genetic cause or aging (aging).
Baldness is also one of most severe side effect of cancer therapy, also causes because of the various chemotherapeutic of administration (chemotherapeutic agent).Because chemotherapeutic affects cell fission (cytokinesis), so chemotherapeutic can cause side effect in the vigorous tissue of the cell fission such as such as marrow (bone marrow), hair, nail (fingernail), toenail (toenail), skin or gi tract (gastrointestinal tract), and therefore cause baldness.Although the patient accepting chemotherapy (chemotherapy) of more than 80% or 80% is maximum misery depending on baldness, not yet develop the method for the bald head of effectively prevention or the initiation of therapeutical chemistry therapy.
Baldness can occur in chemotherapeutic rear about 2 to 4 weeks.Hair just can grow after 3 to 6 months after chemotherapy terminates.The degree of baldness changes with the amount of used medicine, medicine and dispensing time-histories.Cause the pharmaceutical pack of height baldness containing endoxan (cyclophosphamide), Zorubicin (doxorubicin), cis-platinum (cisplatin), cytosine arabinoside (cytosine arabinoside) and etoposide (etoposide).Even if said medicine also can cause baldness when local administration.For example, chemotherapeutic can affect the cell fission of hair follicle, thus it is dead to cause hair follicle cell, maybe can promote to change catagen (catagen) into from vegetative period (anagen).
The method of current clinical practice treatment baldness is: external application medicine, oral pharmaceutical and Hair transplantation (hair implantation), but respectively has its limitation and shortcoming.Min Nuoxidai (Minoxidil) or that male amine (Finasteride) luxuriant and rich with fragrance are two kinds of hair tonic medicaments that current U.S. FDA is checked and approved.Patient uses external application Min Nuoxidai and that male drug amine of oral phenanthrene need all continue to use just effective, can not drug withdrawal.In addition, after using Min Nuoxidai or that male amine luxuriant and rich with fragrance, hair cannot be made to become dense, only can alleviate phenomenon of shaving one's head, or only grow thin hair, and the side effects such as meeting sexual disorders, hirsutism (hypertrichosis), Fetal Defects.Therefore be not suitable for Women of Childbearing Age to use.Moreover autologous hair transplantation operation (hair implantation) can send out place's scar moving, and the postsurgical recovery time is long, need that Repeated Operation, operating time are long, expense is many.
Summary of the invention
The invention provides and a kind ofly win the method that peptide is applied to hair tonic, (as scar, the postsurgical recovery time is long, needs Repeated Operation need not to face every problem of autologous hair transplantation operation ... Deng).
The invention provides and a kind ofly win the method that peptide is applied to hair tonic.This victory peptide is selected from hair tonic victory peptide (HGP), the full sequence that this hair tonic victory peptide (HGP) is aminoacid sequence SEQ ID No:1 or partial sequence.
The present invention separately provides a kind of and wins the method that peptide is applied to hair tonic.This victory peptide is selected from hair tonic victory peptide (HGP), and this hair tonic victory peptide (HGP) aminoacid sequence is about 90% to 99% similar between aminoacid sequence SEQ ID No:1.Similar (similarity) of the present invention is the statistics carried out analyzing with Shimadzu LCMS2010 software and obtain.
The present invention provides again a kind of pharmaceutical composition being used for the treatment of baldness.This pharmaceutical composition comprises hair tonic victory peptide (HGP) and phosphoric acid salt.The full sequence that this hair tonic victory peptide (HGP) is aminoacid sequence SEQ ID No:1 or partial sequence.
The present invention reoffers a kind of pharmaceutical composition being used for the treatment of baldness.This pharmaceutical composition comprises hair tonic victory peptide (HGP) and monophosphate.This hair tonic victory peptide (HGP) aminoacid sequence is about 90% to 99% similar between aminoacid sequence SEQ ID No:1.
Other object of the present invention, part will be stated in follow-up explanation, and part by apparent in description of contents, or can be learnt by enforcement of the present invention.Each aspect of the present invention can to utilize in appended claim specifically noted assembly and combination and understand and reach.Need to understand, the use that the general remark first stated and following detailed description are all only for example, and be not used to limit the present invention.
Summarize technical characteristic of the present invention and advantage quite widely above, describe in detail in order to do the present invention made hereafter and obtained better understanding.Other technical characteristic and the advantage that form claim target of the present invention will be described in hereafter.Persond having ordinary knowledge in the technical field of the present invention should be appreciated that, the concept that hereafter discloses and specific embodiment quite easily can be utilized to can be used as revise or design other structure or processing procedure and realize the object identical with the present invention.Persond having ordinary knowledge in the technical field of the present invention also should be appreciated that, this kind of equivalent construction cannot depart from the spirit and scope of the present invention that appended claim defines.
Accompanying drawing explanation
When and when reading with each alterations, can better understanding aforementioned summary of the present invention and describing in detail above.For reaching illustration purpose of the present invention, each graphic inner figure is painted with existing genus preferably each specific embodiment.So should be appreciated that the present invention is not limited to painted accurate row and puts mode and equipment configuration.
Fig. 1 display is according to the schematic diagram of the experimental procedure of one embodiment of the invention;
Fig. 2 display is according to the schematic diagram of six blocks of the mouse skin of back of one embodiment of the invention;
Fig. 3 display is according to the schematic diagram of the immunofluorescence dyeing of one embodiment of the invention, the cell marking (marker CK15) of its display hair follicle (hair follicle) stem cell, after being subject to aminoacid sequence SEQ ID No:1 victory peptide process hair follicle stem cells, obviously activated.Therefore aminoacid sequence SEQ ID No:1 wins the regenerative process (regeneration) of Toplink activation hair follicle stem cells;
The schematic diagram of the immunofluorescence dyeing that Fig. 4 display marks according to the Wnt3a of one embodiment of the invention.Then promote hair regeneration in order to how analysis of amino acid sequence SEQ ID No:1 victory peptide activates hair follicle stem cells, whether immunofluorescence dyeing is then used for analyzing Win/ β-catenin signal bang path and is activated.As shown in the arrow of Fig. 4, Wnt3a is obviously activated in hair follicle stem cells;
The schematic diagram of the immunofluorescence dyeing that Fig. 5 display marks according to the β-catenin of one embodiment of the invention.Due to the downstream gene that β-catenin is in Win signal bang path, therefore the activation of β-catenin can start Win signal bang path, and then hair follicle stem cells is regenerated.As shown in Figure 5, aminoacid sequence SEQ ID No:1 wins the process that peptide is observed for activation or regeneration hair follicle stem cells and has the effect of enhancement;
Fig. 6 display is according to the schematic diagram of the TCF reporter assay (reporter assay) of human hair follicle keratinocyte (HHFK) strain of one embodiment of the invention.TOP represents reporter gene and has the bound site (binding site) that can supply β-catenin bond.FOP represents in reporter gene and suddenlys change for the bound site of β-catenin bond and destroy, and therefore β-catenin cannot bond, and then as a kind of negative control group (negative control).CTL represents HHFK cell strain and there is no and be subject to any stimulator or victory peptide process.IPept-1 represents HHFK cell strain to be stimulated via aminoacid sequence SEQ ID No:1 victory peptide.With reference to the activity of relative fluorescence element enzyme, via SEQ ID No:1 win peptide to stimulate or activity that HHFK cell strain after processing can be observed its β-catenin also improves;
Fig. 7 display is according to the schematic diagram of the TCF reporter assay (reporter assay) of human skin keratinocyte (HaCaT) strain of one embodiment of the invention.TOP represents reporter gene and has the bound site (binding site) that can supply β-catenin bond.FOP represents in reporter gene and suddenlys change for the bound site of β-catenin bond and destroy, and therefore β-catenin cannot bond, and then as a kind of negative control group (negative control).CTL represents HaCaT cell strain and there is no and be subject to any stimulator or victory peptide process.IPept-1 represents HaCaT cell strain to be stimulated via aminoacid sequence SEQ ID No:1 victory peptide.With reference to the activity of relative fluorescence element enzyme, via SEQ ID No:1 win peptide to stimulate or activity that HaCaT cell strain after processing can be observed its β-catenin also improves;
Fig. 8 shows the schematic diagram tested according to the RT-PCR of the scavenger cell (macrophages) of one embodiment of the invention.Ctl represents scavenger cell without being subject to any stimulator or the process of victory peptide.IPept-1 represents scavenger cell to be stimulated via aminoacid sequence SEQ ID No:1 victory peptide.According to the result of RT-PCR test, aminoacid sequence SEQ ID No:1 wins the gene expression that peptide can activate Wnt16 and Wnt7b in scavenger cell; And
Fig. 9 shows the schematic diagram tested according to the QRT-PCR of the scavenger cell of one embodiment of the invention.CTL represents scavenger cell without being subject to any stimulator or the process of victory peptide.IPept-1 represents scavenger cell to be stimulated via aminoacid sequence SEQ ID No:1 victory peptide.According to the result of QRT-PCR test, aminoacid sequence SEQ ID No:1 wins the gene expression that peptide can promote Wnt16 in scavenger cell.
Embodiment
Embodiments of the invention system coordinates institute's accompanying drawings to set forth details hereinafter.But embodiments of the invention must not need whole technical characteristics to implement.In other embodiments, some known method, structure and technology can not show and cause misunderstanding." this embodiment " and " other embodiment " etc. mentioned by specification sheets, mean to be included in special characteristics, sequence or feature relevant described in this embodiment of the present invention.The phrase of " in this embodiment " that occur everywhere in specification sheets, the inevitable embodiment that all finger is identical.
The present invention is that a kind of peptide that wins is applied to the method for hair tonic and is used for the treatment of the pharmaceutical composition of baldness in the direction that this inquires into.In order to the present invention can be understood up hill and dale, by following description, detailed step and sequence are proposed.Apparently, the specific details that the those skilled in the art that execution of the present invention is not defined in association area has the knack of.On the other hand, well-known sequence or step are not described in details, to avoid the restriction causing the present invention unnecessary.Preferred embodiment of the present invention can be described in detail as follows, but except these are described in detail, the present invention can also implement in other embodiments widely, and scope of the present invention not circumscribed, it is as the criterion with claim.
Hair tonic victory peptide in victory peptide disclosed by the present invention, hair tonic victory peptide (Hair growth peptide, HGP) or pharmaceutical composition is but is not limited to utilize mass spectrograph to confirm its specified molecular weight.Specifically, this case utilize US business to apply life company (mass spectrograph (Time-of-Flight mass spectrometry, Sciex QSTAR PULSAR Quadrupole) of Applied Biosystems carries out the confirmation of molecular weight.Get appropriate sample be dissolved in formic acid (formic acid) solution and form sample solution, under special circumstances, also serine protease (Serine proteases) can be utilized, serine/threonine protein enzyme (Threonine proteases), L-Cysteine HCL Anhydrous (Cysteine proteases), aspartate protease (Aspartate proteases), after the enzymes such as hydroxyproline enzyme (Glutamic proteases) and metalloprotease (Metalloproteases) process sample, carry out the confirmation step of above-mentioned molecular weight again.This sample solution (about 5 μ l) imports in above-mentioned mass spectrograph.After mass spectrograph measures sample solution, data is the determination mode of specific victory peptide in the mass spectrum utilizing computer software (such as Shimadzu LCMS2010) analysis to measure, and such as in measured mass spectrum, the numerical value of the mass-to-charge ratio of at least two peak values may correspond in the mass spectrum measured in this specific victory peptide or utilization and has specific victory peptide in the mode confirmatory sample of mass-to-charge ratio close to the mass-to-charge ratio of specific victory peptide.For example, the molecular weight of aminoacid sequence SEQ ID No:1 is 1218.43, and when this victory peptide is with two electric charges, its mass-to-charge ratio is about 610.15.Mass-to-charge ratio (m/z) formula is (m/z)=(mass M+electric charge n)/electric charge n.Being event, when occurring in mass spectrum that mass-to-charge ratio is about peak value (peak) of 610.15, aminoacid sequence SEQ ID No:1 can being had in confirmatory sample.In addition, the molecular weight of other aminoacid sequence can refer to table 1.
Similarly, the sample of pharmaceutical composition also can be confirmed by the measuring process of above-mentioned hair tonic victory peptide.But, after pharmaceutical composition also can first dilute in some cases, then carry out above-mentioned measuring process.
The phosphoric acid salt that pharmaceutical composition of the present invention comprises is selected from potassiumphosphate (KH
2pO
4), phosphoric acid receives (Na
2hPO
42H
2o) and mixing salt.
The vehicle (Excipients) of pharmaceutical composition of the present invention is increase the homogeneity of pharmaceutical composition, stability and the pungency of minimizing pharmaceutical composition, the material of unpleasant odor.Vehicle of the present invention be nontoxicity, nonirritant, no antigen, without sensitization, without mutagenicity and parmacodynamics-less activity, and do not hinder drug effect performance.
Based on mentioned above principle, vehicle system of the present invention is selected from lactose (Lactose), dry starch (Starch), starch paste (Starch paste), dextrin (Dextrin), cyclodextrin (Cyclodexrtin), pregelatinized Starch (Pregelatinized starch), by methyl starch sodium (Carboxymethyl Starch Sodium), carboxy starch propionic ester (HydroXypropy Starch, be called for short HPS), Microcrystalline Cellulose (Microcrystalline Cellulose), carboxymethyl cellulose (Carboxy Methyl Cellulose.Be called for short CMC), the mixing of croscarmellose sodium (Cross-linked Carboxymethy Cellulose Sodium), low-substituted hydroxypropyl cellulose (Lowsubstitued Hydroxypropyl Cellulose) and above-mentioned at least two kinds of vehicle.
The confirmation method of above-mentioned vehicle is for being selected from chromatography method (Chromatography Methods), spectroscopic analysis (Spectrophotometry Methods), spectroscope spectroscopic analysis (Spectroscopy Methods) and volumetry.
Hair tonic victory peptide in victory peptide of the present invention, hair tonic victory peptide (Hair growth peptide, HGP) or pharmaceutical composition is but is not limited to utilize solid phase polypeptide synthesis (solid phase peptide synthesis) to be also called U.S. sharp fell's method (Merrifield method).In other embodiments, the mode that the hair tonic victory peptide in victory peptide, hair tonic victory peptide (Hair growth peptide, HGP) or pharmaceutical composition also can be showed by protein generates.Due to solid phase polypeptide synthesis or the method for protein technique of expression all with known at present consistent, do not repeat them here.In addition, hair tonic of the present invention victory peptide also can the synthesized or performance by industry Ke Luonai International Technology company limited (Kelowna), usually knows that the knowledgeable can above assist prepare hair tonic of the present invention victory peptide easily therefore in this field.Be event, the present invention need not clearly demonstrate preparation process and the preparation condition of hair tonic of the present invention victory peptide reality.
Pharmaceutical composition of the present invention is but is not limited to solution dosage, hair tonic victory peptide system is dissolved in phosphate buffered saline buffer (PBS solution) 4 milliliters makes hair tonic victory peptide concentration be 2mM to 8 milliliters, after be diluted to 0.2mM with 2mM again, and be prepared into pharmaceutical composition of the present invention.
Hair regeneration (hair regeneration) mouse experimentation on animals pattern (mouse model) that experiment model of the present invention is developed for the just bright academician of application USC clock.
Female mouse that the mouse that this mouse experimentation on animals pattern adopts: C57BL/6 eight weeks is large.
According to document (Muller-Rover et al., 2001; Plikus et al., 2009) report, all pulls out or after hair with the female mouse skin of back of cured removal, hair follicle will enter vegetative period (anagen) after the 7th day.Now the hair of female mouse skin of back will regrow out.About 14 days vegetative period.Above-mentioned steps is by the synchronization in vegetative period (synchronization) of whole hair follicles.
The hair follicle of female mouse skin of back will enter and absolutely not react resting stage (refractory telogen) after vegetative period.Absolutely not react resting stage (refractory telogen) and about have 28 days.The present invention utilizes drug treating whether to contribute to hair growth in the hair follicle absolutely not reacting resting stage to observe medicine.
As shown in Figure 1, after the hair follicle of female mouse skin of back is all pulled out, entered in the 21st day and the hair of female mouse skin of back is rejected.As shown in Figure 2, the skin of back of rejecting hair is divided into six blocks, and the distance of each block has more than 3 centimeters at least, to avoid interfering with each other.Each block will apply medicine 10 days continuously.The mode applied is including but not limited to injection (50 microlitre) and smear (10 microlitre).In addition, the dosage applying medicine every day, including but not limited to two kinds of dosage, is respectively high dosage (2,000 μM) and low dosage (200 μMs).
In order to ensure experiment confidence level and avoid the error in manual operation, as shown in Figure 2, first block 1 applies Cyclosporine (cyclosporine) 10 times (every day 1 time) continuously, wherein the present invention is using Cyclosporine (cyclosporine) as positive control group (positive control), the concentration of positive control group is weight percentage 0.5% (with 100% alcohol), smears 10 microlitres at every turn; Second block 2 smears hair tonic victory peptide or the pharmaceutical composition 10 times (every day 1 time) of high dosage continuously; 3rd block 3 smears hair tonic victory peptide or the pharmaceutical composition 10 times (every day 1 time) of low dosage continuously; 4th block 4 smears 100% alcohol 10 times (every day 1 time, smearing 10 microlitres) continuously at every turn, and this group is as negative control group (negative control); 5th block 5 injects hair tonic victory peptide or the pharmaceutical composition 10 times (every day 1 time) of high dosage continuously; And the hair tonic of the 6th block 6 continuous injection low dosage wins peptide or pharmaceutical composition 10 times (every day 1 time).Above-mentioned hair tonic victory peptide is all identical victory peptide sequence.
Based on document (Maurer et al., 1997) report, if smear the Cyclosporine of 10 days continuously at the skin of the mouse back of the body, the hair of its skin will be induced and regenerate.Therefore the hair tonic all for screening wins peptide or pharmaceutical composition will utilize above-mentioned experiment model to carry out testing and record the situation of hair regeneration every day.Because the absolutely not reaction resting stage (refractory telogen) of mouse is approximately 28 days, apply medicine if therefore start when being observed without the phenomenon of any hair regeneration after 30 days, this hair tonic victory peptide or pharmaceutical composition are then considered as not having trichogenous ability.In other words, start to apply medicine when having the phenomenon of any hair regeneration to be observed in 30 days, then the hair tonic victory peptide of this experimental group or pharmaceutical composition are considered as having trichogenous ability.
Wnt gene family, for many etap, comprises hair follicle growth and differentiation, all plays the part of important role.General Wnt signal will cause β-catenin protein stabilization and β-catenin is assembled, and then cause the nuclear translocation (nuclear translocation) of LEF/TCF transcription factor and activate and regulatory gene performance.Academic journal inference Wnt/ β-catenin has important function (Kishimoto et al.2000 in hair kenel and differentiation; Fuchs et al.2001; Millar2002).
In addition, hair growth is relevant to Wnt/ β-catenne element (β-catenin) and bone morphogenetic protein 2/4 (BMP2/4) signal bang path, and therefore hair tonic of the present invention victory peptide or pharmaceutical composition seem likely to carry out regulation and control hair growth through signal bang path thus.In other words, hair tonic victory peptide of the present invention or pharmaceutical composition may affect Wnt/ β-catenne element (β-catenin) and bone morphogenetic protein 2/4 (BMP2/4) signal bang path via acting on hair follicle.
Related amino acid sequence is applied to the skin keratinocytes strain (HaCaT) of the mankind, follicle keratinocytes strain (HHFK) and hair follicle microenvironment scavenger cell (Macrophage) by this case further, verifies that those aminoacid sequences victory peptide brings out hair growth situation.
Aminoacid sequence SEQ ID No:1 wins peptide and is used in above-mentioned experiment, to process or to stimulate HHFK cell, HaCaT cell and scavenger cell, and the hair growth mechanism being subject to aminoacid sequence SEQ ID No:1 victory peptide and bringing out for deliberation.
After C57BL/6 female mouse injection SEQ ID No:1 wins peptide, carry out immunofluorescence dyeing for the target CK15 in female rat tissue, and then observe the genes such as Wnt3a, Wnt/ β-catenin and whether activated.
In the present invention, HHFK, HaCaT and scavenger cell are used as cell pattern, related mechanism for deliberation.Reporter assay (reporter assay) and QRT-PCR system are used as biological activity test, win peptide how to promote hair growth for analysis of amino acid sequence SEQ ID No:1.
As shown in Figure 3, after immunofluorescence dyeing is presented at and is subject to aminoacid sequence SEQ ID No:1 victory peptide process hair follicle stem cells, the cell marking (marker CK15) of hair follicle (hair follicle) stem cell is obviously activated.Therefore, aminoacid sequence SEQ ID No:1 wins the regenerative process (regeneration) of Toplink activation hair follicle stem cells.In order to analysis of amino acid sequence SEQ ID No:1 wins the regenerative process how peptide activates hair follicle stem cells, therefore carry out the immunofluorescence dyeing experiment of Win/ β-catenin signal bang path.As shown in Figure 4, Wnt3a obviously activates in hair follicle stem cells.Because β-catenin is the downstream gene in Win signal bang path, therefore the activation of β-catenin can start Win signal bang path, and then hair follicle stem cells is regenerated.As shown in Figure 5, β-catenin wins peptide process by SEQ ID No:1 and activates.In other words, SEQ ID No:1 wins effect that peptide has activation Win/ β-catenin signal bang path, and then the regenerative process of activation hair follicle stem cells.
In reporter assay as shown in figs. 6 and 7, the dosage 50ng/ml of Wnt3a is forward control group.According to result, the SEQ ID No:1 of 200 μMs wins the activity that peptide can promote β-catenin in HaCaT cell and HHFK cell.
After scavenger cell to win peptide (iPet-1) processes 8 hours via the SEQ ID No:1 of 200 μMs, Wnt family (such as Wnt1, Wnt2, Wnt3a, Wnt4, Wnt6, Wnt7a, Wnt7b, Wnt10a, Wnt10b and Wnt16) gene regulating system via RT-PCR and QRT-PCR experiment detected, result is as shown in figures 8 and 9.Can be observed, the transcription stage of Wnt16 and Wnt7a is obviously promoted via iPet-1 process.Therefore aminoacid sequence SEQ ID No:1 victory peptide is proved and can activates Win/ β-catenin signal bang path, and then regeneration hair follicle stem cells is for hair growth.
Table 1 shows the numbering of sequence table of the present invention and the contrast relationship of aminoacid sequence.
Table 1
| Sequence table is numbered | Aminoacid sequence (from aminoterminal to carboxyl terminal) | Molecular weight (molecular weight) |
| SEQ?ID?No:1 | PSTHVLITHTI | 1218.43 |
| SEQ?ID?No:2 | HVLIT | 581.72 |
| SEQ?ID?No:3 | VLITH | 581.72 |
| SEQ?ID?No:4 | LITHT | 583.69 |
| SEQ?ID?No:5 | STHVL | 555.64 |
| SEQ?ID?No:6 | PSTHVLITHTISRI | 1574.86 |
| SEQ?ID?No:7 | ITHTI | 583.69 |
| SEQ?ID?No:8 | PSTHVL | 652.75 |
| SEQ?ID?No:9 | PSTHVLI | 765.91 |
| SEQ?ID?No:10 | PSTHVLIT | 867.12 |
| SEQ?ID?No:11 | PSTHVLITH | 1004.16 |
| SEQ?ID?No:12 | PSTHVLITHT | 1105.27 |
| SEQ?ID?No:13 | STHVLITHTI | 1121.31 |
| SEQ?ID?No:14 | THVLITHTI | 1034.23 |
| SEQ?ID?No:15 | HVLITHTI | 933.13 |
| SEQ?ID?No:16 | VLITHTI | 795.98 |
| SEQ?ID?No:17 | LITHTI | 696.85 |
| SEQ?ID?No:18 | PSTHVLGSFGS | 1088.19 |
| SEQ?ID?No:19 | PSTHVLIGSFG | 1114.28 |
| SEQ?ID?No:20 | PSTHVLITGSF | 1158.33 |
| SEQ?ID?No:21 | PSTHVLITHGS | 1148.29 |
| SEQ?ID?No:22 | PSTHVLITHTG | 1162.32 |
| SEQ?ID?No:23 | PSTHVLSFGSG | 1088.19 |
| SEQ?ID?No:24 | PSTHVLIFGSG | 1114.28 |
| SEQ?ID?No:25 | PSTHVLITGSG | 1068.20 |
| SEQ?ID?No:26 | PSTHVLITHSG | 1148.29 |
| SEQ?ID?No:27 | PSTHVLITHTS | 1192.35 |
| SEQ?ID?No:28 | PSTHVLITHTISR | 1461.70 |
| SEQ?ID?No:29 | PSTHVLITHTIS | 1305.51 |
| SEQ?ID?No:30 | GSTHVLITHTI | 1178.36 |
| SEQ?ID?No:31 | GSFHVLITHTI | 1224.44 |
| SEQ?ID?No:32 | GSFGVLITHTI | 1144.35 |
| SEQ?ID?No:33 | GSFGFLITHTI | 1192.39 |
| SEQ?ID?No:34 | GSFGSFITHTI | 1166.31 |
| SEQ?ID?No:35 | FSTHVLITHTI | 1268.49 |
| SEQ?ID?No:36 | FGTHVLITHTI | 1238.46 |
| SEQ?ID?No:37 | FGSHVLITHTI | 1224.44 |
| SEQ?ID?No:38 | FGSFVLITHTI | 1234.47 |
| SEQ?ID?No:39 | FGSFGLITHTI | 1192.39 |
| SEQ?ID?No:40 | FGSFGSITHTI | 1166.31 |
| SEQ?ID?No:41 | PSTHVLLTHTI | 1218.43 |
The contrast relationship that the experimental group numbering that table 2 shows hair tonic of the present invention victory peptide and pharmaceutical composition thereof is numbered with sequence table.The similarity of sequence of the present invention is the statistics carried out analyzing with Shimadzu LCMS2010 software and obtain.
Table 2
| Experimental group is numbered | Sequence table is numbered |
| P1 | SEQ?ID?No:1 |
| P2 | SEQ?ID?No:2 |
| P3 | SEQ?ID?No:3 |
| P4 | SEQ?ID?No:4 |
| P5 | SEQ?ID?No:5 |
| P6 | SEQ?ID?No:6 |
| P7 | SEQ?ID?No:7 |
| P8 | SEQ?ID?No:8 |
| P9 | SEQ?ID?No:9 |
| P10 | SEQ?ID?No:10 |
| P11 | SEQ?ID?No:11 |
| P12 | SEQ?ID?No:12 |
| P13 | SEQ?ID?No:13 |
| P14 | SEQ?ID?No:14 |
| P15 | SEQ?ID?No:15 |
| P16 | SEQ?ID?No:16 |
| P17 | SEQ?ID?No:17 |
| P18 | SEQ?ID?No:18 |
| P19 | SEQ?ID?No:19 |
| P20 | SEQ?ID?No:20 |
| P21 | SEQ?ID?No:21 |
| P22 | SEQ?ID?No:22 |
| P23 | SEQ?ID?No:23 |
| P24 | SEQ?ID?No:24 |
| P25 | SEQ?ID?No:25 |
| P26 | SEQ?ID?No:26 |
| P27 | SEQ?ID?No:27 |
| P28 | SEQ?ID?No:28 |
| P29 | SEQ?ID?No:29 |
| P30 | SEQ?ID?No:30 |
| P31 | SEQ?ID?No:31 |
| P32 | SEQ?ID?No:32 |
| P33 | SEQ?ID?No:33 |
| P34 | SEQ?ID?No:34 |
| P35 | SEQ?ID?No:35 |
| P36 | SEQ?ID?No:36 |
| P37 | SEQ?ID?No:37 |
| P38 | SEQ?ID?No:38 |
| P39 | SEQ?ID?No:39 |
| P40 | SEQ?ID?No:40 |
| P41 | SEQ?ID?No:41 |
The step as earlier figures 1 and Fig. 2 is adopted to test each for above-mentioned experimental group P1 to P41 group, and observe result as following table 3, digital X in table 3 represents the phenomenon (such as, X=5 represents the phenomenon that the 5th day observes hair regeneration) observing hair regeneration for X days.And NA representative is not yet analyzed, wait further experiment.In addition, in the experimental result in table 3, positive control group all observed the phenomenon of hair regeneration in 30 days, and therefore experimental result should be accepted and believed.In addition, "None" representative is via still absent hair growth in after victory peptide process 30 days.
Table 3
| Experimental group is numbered | Inject or smear (high dosage) |
| P1 | 17 |
| P2 | 17 |
| P3 | 17 |
| P4 | 17 |
| P5 | 19 |
| P6 | 19 |
| P7 | 17 |
| P8 | 15 |
| P9 | Nothing |
| P10 | Nothing |
| P11 | 19 |
| P12 | 19 |
| P13 | Nothing |
| P14 | Nothing |
| P15 | Nothing |
| P16 | Nothing |
| P17 | 22 |
| P18 | 22 |
| P19 | Nothing |
| P20 | Nothing |
| P21 | 23 |
| P22 | 23 |
| P23 | Nothing |
| P24 | Nothing |
| P25 | 22 |
| P26 | 22 |
| P27 | Nothing |
| P28 | Nothing |
| P29 | 22 |
| P30 | 22 |
| P31 | Nothing |
| P32 | Nothing |
| P33 | Nothing |
| P34 | Nothing |
| P35 | 15 |
| P36 | 15 |
| P37 | Nothing |
| P38 | Nothing |
| P39 | Nothing |
| P40 | Nothing |
| P41 | 19 |
Technology contents of the present invention and technical characterstic have disclosed as above, but persond having ordinary knowledge in the technical field of the present invention should be appreciated that, not deviating from the spirit and scope of the invention that claims define, teaching of the present invention and disclose and can do all replacements and modification.Such as, the enforcement that the many assemblies disclosed above can be different or replaced with the sequence of other identical function, or adopt the combination of above-mentioned two kinds of modes.
In addition, the interest field of this case is not limited to the sequence of the specific embodiment disclosed above.Persond having ordinary knowledge in the technical field of the present invention should be appreciated that, based on teaching of the present invention and announcement sequence, no matter exist now or developer in the future, itself and this case embodiment announcement person perform the identical function of essence in the mode that essence is identical, and reach the identical result of essence, also can be used in the present invention.Therefore, following claim system is in order to contain this type of sequence.
Nomenclature
1 first block
2 second blocks
3 the 3rd blocks
4 the 4th blocks
5 the 5th blocks
6 the 6th blocks
Claims (20)
1. victory peptide of the hair tonic for hair tonic (HGP), comprises full sequence or the partial sequence of aminoacid sequence SEQ ID No:1.
2. hair tonic victory peptide according to claim 1, the carboxyl terminal of wherein said aminoacid sequence SEQ ID No:1 is deleted or is replaced 1 to 3 or 5 any amino acid.
3. hair tonic victory peptide according to claim 1, the carboxyl terminal of wherein said aminoacid sequence SEQ ID No:1 adds 1 to 3 any amino acid.
4. the hair tonic victory peptide described in claim 1 or 2, the aminoterminal of wherein said aminoacid sequence SEQ ID No:1 is deleted or is replaced 1 or 3 to 6 any amino acid.
5. hair tonic victory peptide according to claim 2, wherein said hair tonic victory peptide (HGP) is selected from SEQ ID No:2, SEQ ID No:3, SEQ ID No:4 and SEQ ID No:5.
6. hair tonic victory peptide according to claim 3, wherein said hair tonic victory peptide (HGP) is SEQ ID No:6.
7. hair tonic victory peptide according to claim 4, wherein said hair tonic victory peptide (HGP) is selected from SEQ ID No:2, SEQ ID No:3, SEQ ID No:4, SEQ ID No:5 and SEQ ID No:7.
8. hair tonic victory peptide according to claim 1, the dosage of wherein said hair tonic victory peptide (HGP) is between 200 μMs to 2000 μMs.
9. hair tonic victory peptide according to claim 1, wherein said hair tonic victory peptide (HGP) acts on hair follicle.
10. hair tonic according to claim 1 victory peptide, wherein said hair tonic victory peptide (HGP) aminoacid sequence is about 90% to 99% similar between aminoacid sequence SEQ ID No:1.
11. 1 kinds, for the pharmaceutical composition of hair tonic, comprise:
Hair tonic victory peptide (HGP), the full sequence that wherein said hair tonic victory peptide (HGP) is aminoacid sequence SEQ ID No:1 or partial sequence.
12. pharmaceutical compositions for hair tonic according to claim 11, the carboxyl terminal of wherein said aminoacid sequence SEQ ID No:1 is deleted or is replaced 1 to 3 or 5 any amino acid.
13. pharmaceutical compositions for hair tonic according to claim 11, the carboxyl terminal of wherein said aminoacid sequence SEQ ID No:1 adds 1 to 3 any amino acid.
14. pharmaceutical compositions for hair tonic according to claim 11, the aminoterminal of wherein said aminoacid sequence SEQ ID No:1 is deleted or is replaced 1 or 3 to 6 any amino acid.
15. pharmaceutical compositions for hair tonic according to claim 12, wherein said hair tonic victory peptide (HGP) is selected from SEQ ID No:2, SEQ ID No:3, SEQ ID No:4 and SEQ ID No:5.
16. pharmaceutical compositions for hair tonic according to claim 13, wherein said hair tonic victory peptide (HGP) is SEQ ID No:6.
17. pharmaceutical compositions for hair tonic according to claim 14, wherein said hair tonic victory peptide (HGP) is selected from SEQ ID No:2, SEQ ID No:3, SEQ ID No:4, SEQ ID No:5 and SEQ ID No:7.
18. pharmaceutical compositions for hair tonic according to claim 11, the dosage of wherein said hair tonic victory peptide (HGP) is between 200 μMs to 2000 μMs.
19. pharmaceutical compositions for hair tonic according to claim 11, wherein said hair tonic victory peptide (HGP) acts on hair follicle.
20. pharmaceutical compositions for hair tonic according to claim 11, wherein said hair tonic victory peptide (HGP) aminoacid sequence is about 90% to 99% similar between aminoacid sequence SEQ ID No:1.
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| Application Number | Priority Date | Filing Date | Title |
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| TW102119875 | 2013-06-05 | ||
| TW102119875 | 2013-06-05 | ||
| TW103108089A TWI516272B (en) | 2013-06-05 | 2014-03-10 | Method and pharmaceutical composition for hair growth |
| US14/203,224 | 2014-03-10 | ||
| US14/203,224 US9827181B2 (en) | 2013-06-05 | 2014-03-10 | Method and pharmaceutical composition for hair growth |
| TW103108089 | 2014-03-10 |
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| CN104231048A true CN104231048A (en) | 2014-12-24 |
| CN104231048B CN104231048B (en) | 2017-05-24 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110338343A (en) * | 2019-07-25 | 2019-10-18 | 理想如米生物科技(深圳)有限公司 | A kind of nutrient powder of functions of nourishing hair and growing hair and body weight control |
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| CN1215404A (en) * | 1996-04-03 | 1999-04-28 | 佩普里瑟奇公司 | Non-dendritic backbone piptide carrier |
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| CN110338343A (en) * | 2019-07-25 | 2019-10-18 | 理想如米生物科技(深圳)有限公司 | A kind of nutrient powder of functions of nourishing hair and growing hair and body weight control |
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